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Narcissistic personality disorder For patient information click here \| Narcissistic Personality Disorder\| WikiDoc Resources for Narcissistic personality disorder Evidence Based Medicine Guidelines / Policies / Govt Patient Resources / Community Healthcare Provider Resources Continuing Medical Education (CME) Experimental / Informatics Synonyms and Keywords: NPD; self-centered personality disorder; self-involved personality disorder; egotistic personality disorder; egotistitical personality disorder; narcissistic; narcissism; Narcissus; self-centered; self-involved; egotistic; egotistical; narcissistic personality Narcissistic personality disorder (NPD) is a mental illness characterized by an extreme focus on oneself, chronic arrogance and feelings of superiority, a lack of empathy or consideration for others, and a longstanding need to be admired and respected. NPD is a maladaptive, rigid, and persistent condition that may cause significant distress and functional impairment. Narcissistic personality disorder is a "cluster B" personality disorder. The ICD-10 (International Classification of Mental and Behavioural Disorders, published by the World Health Organisation in Geneva in 1992, regards narcissistic personality disorder (NPD) as "a personality disorder that fits none of the specific rubrics," relegating it to the category known as "Other specific personality disorders." This category also includes the eccentric, "haltlose," immature, passive-aggressive, and psychoneurotic personality disorders. Men are more commonly afflicted with NPD than women. The primary consequences of NPD are social. Interpersonal relationships often suffer due to the patient’s sense of entitlement and disregard for the feelings of others, which may manifest as manipulation, infidelity, or violence. Disruptions to relationships may give rise to anxiety or depression in an NPD patient. The term narcissistic personality disorder was first used by Heinz Kohut in 1971. In 1980, NPD became a diagnostic category as defined by the DSM. From the publication of the DSM-III to the DSM-IV, which was released in 1994, professional thought shifted from considering the primary characteristic of NPD an inability to empathize with others to an unwillingness to consider or try to understand others' feelings. No formal classification scheme exists for NPD. It has been suggested that certain neurological defects that are common in NPD patients (i.e., frontolimbic dysfunctions) may predispose sufferers to such neurodegenerative diseases as dementia. Additional longitudinal studies will be necessary to confirm this association. Common Comorbid Conditions NPD is found in individuals suffering from psychopathy in approximately 21% of cases; in BPD patients in 37-39% of cases; and in substance abuse disorder patients in 11.8% of cases. Mood disorders and PTSD are also commonly comorbid with NPD. Dysthymia is strongly negatively correlated with incidence of NPD. - An oversensitive temperament at birth - Overindulgence and overvaluation by parents - Valued by parents as a means to regulate their own self-esteem - Excessive admiration that is never balanced with realistic feedback - Unpredictable or unreliable caregiving from parents - Severe emotional abuse in childhood - Being praised for perceived exceptional looks or talents by adults - Learning manipulative behaviors from parents Psychologists commonly believe that pathological narcissism results from an impairment in the quality of the person’s relationship with their primary caregivers, usually their parents, in that the parents were unable to form a healthy, empathic attachment to them. This results in the child conceiving of themselves as unimportant and unconnected to others. The child typically comes to believe that he or she has some defect of personality which makes them unvalued and unwanted. - Antisocial personality disorder - NPD patients are most effectively differentiated from ASPD patients by their grandiosity—the propensity to misrepresent themselves or their abilities as unique and superior to others. - NPD patients are more likely to have a steady job and less likely to be institutionalized/incarcerated, while ASPD patients are more likely to actively exploit or abuse other people. - Some experts suggest that ASPD would best be defined as a subgroup of NPD. - Borderline personality disorder - Both NPD and BPD patients are hyper-sensitive and prone to overreact to criticism or perceived slights. They are also less likely to maintain healthy and fulfilling interpersonal relationships. - In BPD, anxiety and depression are endemic to the disorder, whereas in NPD, this type of distress may result as a secondary consequence of the personality disorder, resulting from defects in interpersonal functioning that define the symptomology of NPD. Epidemiology and Demographics The lifetime prevalence of narcissistic personality disorder is from 6,200 per 100,000 (6.2%) of the overall population. NPD most commonly presents in young adults, though it has been observed in patients in their later years as well. Males are more commonly afflicted with NPD than females, though the extent of the disparity is unclear. NPD is most common among Black men and women and Hispanic women. - Male gender (50-75%) - Genetic predisposition - Being unmarried - Excess admiration or neglect by parents - Emotional abuse or manipulation No formal screening recommendations exist for NPD. Natural History, Complications, and Prognosis Current research aims to define the neurological underpinnings of the development of NPD. Certain neurological defects that are common in NPD patients (i.e., frontolimbic dysfunctions) may predispose them to neurodegenerative diseases later in life, particularly dementia. The primary consequences of NPD are social. Interpersonal relationships often suffer due to the patient’s sense of entitlement and disregard for the feelings of others, which may manifest as manipulation, infidelity, or violence. Disruptions to relationships may give rise to anxiety or depression in an NPD patient. Similarly, the behavior and viewpoints of NPD patients may even cause mental health clinicians to harbor negative feelings toward them, which could impair treatment. In some cases, questionable decision-making on the part of patients suffering from NPD may give rise to dire situations or life crises, under which circumstances a patient may require immediate medical attention. A lapse of this nature may also lead to suicide. Narcissism is associated with a broad spectrum of intensity, ranging from socially acceptable and even healthy or professionally beneficial to pathological and destructive. The prognosis of NPD depends on the severity of its presentation in a given patient and the patient’s willingness to seek treatment. Since NPD patients often turn to healthcare to address psychological distress that occurs as a result of personal or academic/professional failures, sufferers who are able to circumvent such failures may be particularly unlikely to seek treatment. Poor prognostic factors include: - Vulnerability in self-esteem - Intolerance to criticism - Feelings of humiliation and self-criticism - Histrionic, borderline, antisocial and/or paranoid personality disorders DSM-V Diagnositic Criteria for Narcissistic Personality Disorder The essential features of a personality disorder are impairments in personality (self and interpersonal) functioning and the presence of pathological personality traits. To diagnose narcissistic personality disorder, the following criteria must be met: While the ICD-10 does not specifically define the characteristics of this personality disorder, it is classified in the category "Other Specific Personality Disorders". ICD-10 states that Narcissistic Personality Disorder is "a personality disorder that fits none of the specific rubrics F60.0-F60.7." That is, this personality disorder does not meet the diagnostic criteria for any of the following: - F60.0 Paranoid Personality Disorder - F60.1 Schizoid Personality Disorder - F60.2 Dissocial (Antisocial) Personality Disorder - F60.3 Emotionally unstable (borderline) Personality Disorder - F60.4 Histrionic Personality Disorder - F60.5 Anankastic (Obsessive-Compulsive) Personality Disorder - F60.6 Anxious (Avoidant) Personality Disorder - F60.7 Dependent Personality Disorder History and Symptoms - Need for admiration - Intense fear of rejection, isolation, and/or loss of admiration or respect - Lack of empathy (coupled with a sense of entitlement that pervades interpersonal relationships) - Tendency to exploit others, possibly subconsciously - Interpersonal distancing and avoidance - Insecurity and vulnerability - Proneness to shame The gold standard for diagnosing NPD is the Diagnostic Interview for Narcissism, which consists of 33 questions evaluating a patient's functional status in five areas: grandiosity, interpersonal relations, reactiveness, affects and moods, and social and moral adaptation. The questionnaire has good internal consistency and acceptable inter-rater reliability. No laboratory findings are considered diagnostic of NPD. Other Diagnostic Studies Assessment modalities include self-reporting through the Personality Diagnostic Questionnaire-4 and Cloninger's Temperament and Character Inventory (TCI). The mainstay of treatment for NPD is psychotherapy, though suffering as a result of the disorder itself is rarely the reason a patient will seek treatment. Commonly, patients are urged to seek psychiatric counsel by family members or loved ones; they may also seek treatment for a different but related condition, such as major depressive disorder or an eating disorder. Treatment aims to help patients control their impulsivity and aggression while encouraging them to be more empathetic and less entitled. No specific medications have proven particularly effective in the treatment of NPD, though medication may be required to treat a co-occurring disorder. Surgery is not indicated for the treatment of NPD. Primary prevention of NPD involves the maintenance of a stable home life throughout childhood and the avoidance of excessive flattery or emotional manipulation by parents or caregivers. No strategies are indicated for the secondary prevention of NPD. - Ronningstam E, Baskin-Sommers AR (2013). "Fear and decision-making in narcissistic personality disorder-a link between psychoanalysis and neuroscience.". Dialogues Clin Neurosci. 15 (2): 191–201. PMC . PMID 24174893. - Gunderson JG, Ronningstam E (2001). "Differentiating narcissistic and antisocial personality disorders.". J Pers Disord. 15 (2): 103–9. PMID 11345846. - Miller JD, Campbell WK, Pilkonis PA (2007). "Narcissistic personality disorder: relations with distress and functional impairment.". Compr Psychiatry. 48 (2): 170–7. PMC . PMID 17292708. doi:10.1016/j.comppsych.2006.10.003. - Kohut, Heinz, The Analysis of the Self, 1971 - Baskin-Sommers A, Krusemark E, Ronningstam E (2014). "Empathy in narcissistic personality disorder: from clinical and empirical perspectives.". Personal Disord. 5 (3): 323–33. PMC . PMID 24512457. doi:10.1037/per0000061. - Poletti M, Bonuccelli U (2011). "From narcissistic personality disorder to frontotemporal dementia: a case report.". Behav Neurol. 24 (2): 173–6. PMID 21606578. doi:10.3233/BEN-2011-0326. - Stinson FS, Dawson DA, Goldstein RB, Chou SP, Huang B, Smith SM; et al. (2008). "Prevalence, correlates, disability, and comorbidity of DSM-IV narcissistic personality disorder: results from the wave 2 national epidemiologic survey on alcohol and related conditions.". J Clin Psychiatry. 69 (7): 1033–45. PMC . PMID 18557663. - "Narcissistic Personality Disorder". Personality Disorders - Narcissistic Personality Disorder. Armenian Medical Network. 2006. Retrieved 2007-02-14. - Johnson, Stephen M PhD (1987). Humanizing the Narcissistic Style. New York: Norton, page 39 - Kernberg OF (1989). "The narcissistic personality disorder and the differential diagnosis of antisocial behavior.". Psychiatr Clin North Am. 12 (3): 553–70. PMID 2678022. - Diagnostic and statistical manual of mental disorders : DSM-5. Washington, D.C: American Psychiatric Association. 2013. ISBN 0890425558. - Balsis S, Eaton NR, Cooper LD, Oltmanns TF (2011). "The Presentation of Narcissistic Personality Disorder in an Octogenarian: Converging Evidence from Multiple Sources.". Clin Gerontol. 34 (1): 71–87. PMC . PMID 21637723. doi:10.1080/07317115.2011.524821. - Livesley, W.J., Jang, K.L., Jackson, D.N. and P.A. Vernon (1993). "Genetic and environmental contributions to dimensions of personality disorder". American Journal of Psychiatry 150, 1826-1831. Abstract online. Accessed June 18, 2006. - Bell CC (1980). "Racism: a symptom of the narcissistic personality disorder.". J Natl Med Assoc. 72 (7): 661–5. PMC . PMID 7392083. - Gunderson JG, Ronningstam E, Bodkin A (1990). "The diagnostic interview for narcissistic patients.". Arch Gen Psychiatry. 47 (7): 676–80. PMID 2360861. - Miller JD, Campbell WK, Pilkonis PA, Morse JQ (2008). "Assessment procedures for narcissistic personality disorder: a comparison of the personality diagnostic questionnaire-4 and best-estimate clinical judgments.". Assessment. 15 (4): 483–92. PMC . PMID 18550845. doi:10.1177/1073191108319022.	2	12	0	0	0	4	0.7817	4	2,977
Megaureter is a medical anomaly whereby the ureter is abnormally dilated. Congenital megaureter is an uncommon condition which is more common in males, may be bilateral, and is often associated with other congenital anomalies. The cause is thought to be aperistalsis of the distal ureter, leading to dilatation. The cutoff value for megaureter is when it is wider than 6 or 7 mm. In an attempt to improve communication and refine the understanding and the significance of megaureter, a working party of pediatric urologists was created. 5 They presented their findings and recommendations in 1976 at an international pediatric urologic seminar in Philadelphia. An agreement was made on standardization of nomenclature and classification of the megaureter. Refluxing megaureter: In this type, the urine flows back up the ureter from the bladder. This backflow, known as vesicoureteral reflux, expands the ureter. Primary obstructed megaureter: The ureter is too narrow where it enters the bladder, causing a blockage of urine flow at that point. Congenital megaureter An infantile ureter measuring more than 7 mm, visualized as a hyperintense tubular structure posterior to the bladder on T2W sequences is termed as a megaureter.( 13 ) It can be further classified as obstructed primary megaureter, refluxing primary megaureter (vesicoureteric reflux), and non-refluxing obstructed primary megaureter.( 13 ). Valid for Submission. Q62.2 is a billable code used to specify a medical diagnosis of congenital megaureter. The code is valid for the year 2020 for the submission of HIPAA-covered transactions. The ICD-10-CM code Q62.2 might also be used to specify conditions or terms like congenital dilatation of ureter, congenital obstructive megaureter, congenital obstructive megaureter without reflux. What is a megaureter?A megaureter means “big ureter” and is a descriptive term, not a diagnosis. The two important questions about megaureter are whether there is reflux (backwash) of urine causing the megaureter or whether there is blockage at the ureterovesical junction causing megaureter (Figure 1). If there is reflux, the diagnosis is “refluxing megaureter” or “megaureter. There is no history of abdominal surgery, trauma or other interventions. Differential diagnosis includes: congenital megaureter bilateral vesicoureteric reflux Considering appearance and age, finding most likely represent congenital megaurete. Congenital giant megaureter: Introduction. Congenital giant megaureter: A rare condition where the patient is born with an abnormally dilated ureter. The anomaly is often associated with other defects or anomalies. The severity of the anomaly is variable. SYN: megaloureter. primary m. independent ureteral dilation; may be nonobstructive or related to congenital distal ureteral obstruction. secondary m. hydroureter secondary to vesicoureteral reflux. A birth defect, also known as a congenital disorder, is a condition present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth defects are divided into two main types: structural disorders in which problems are seen with the shape of a body part and functional. ICD-10 code Q62.2 for Congenital megaureter. Congenital dilatation of ureter. ICD-10. ICD-10-CM 10th Revision 2016. Classification System is used for the classification of active ingredients of drugs according to the organ or system on which they act and their therapeutic. Classification and external resources ICD 10 N28.8, Q62.2 ICD 9. A collection of disease information resources and questions answered by our Genetic and Rare Diseases Information Specialists for Congenital giant megaureter. Code Classification: Congenital malformations, deformations and chromosomal abnormalities (Q00-Q99) Congenital malformations of the urinary system (Q60-Q64) Congen defects of renal pelvis and congen malform of ureter (Q62) Q62.2 Congenital megaureter. Refluxing primary megaureter is caused by a short or absent intravesical ureter, congenital paraureteric diverticulum, or other derangement of the vesicoureteral junction (, 20). Lee et al (, 21 ) assumed that the marked increase in collagen and significant decrease in smooth muscle could be major contributing factors in the pathogenesis of refluxing primary megaureter. Megaureter is a medical anomaly whereby the ureter is abnormally dilated. Congenital megaureter is an uncommon condition which is more common in males, may be bilateral, and is often associated with other congenital anomalies. The cause is thought to be aperistalsis of the distal ureter, leading to dilatation. A functional obstruction at the lower end of the ureter leads to progressive. International Classification of Diseases 10th Revision: Q622. ICD-10 Code Type: Diagnosis. Code description: Congenital megaureter. The Coexistence of Congenital Megacalyces and Primary Megaureter. B Vargas and RL Lebowitz. AJR 147:313-316 August 1986. Talner LB, Gittes RF. Megacalyces. Clin Radiol. 1972;23(3):355-361. Results. Congenital megaureter presents qualitative and quantitative anomalies of the connective tissue and muscular tissue, and also structural modifications of the nervous tissue. Connective tissue.	4	7	0	0	0	8	0.639086	8	1,278
What is HIPAA? HIPAA is the acronym of the Health Insurance Portability and Accountability Act of 1996. The main purpose of this federal statute was to help consumers maintain their insurance coverage, but it also includes a separate set of provisions called Administrative Simplification. This section of the act is aimed at improving the efficiency and effectiveness of the health care system. The key components of Administrative Simplification include: - Standardized electronic transmission of common administrative and financial transactions (such as billing and payments) - Unique health identifiers for individuals, employers, health plans, and heath care providers - Privacy and security standards to protect the confidentiality and integrity of individually identifiable health information The HIPAA regulations apply to: - Health Plans - Health Care Clearinghouses (Entities that facilitate electronic transactions by "translating" data between health plans and providers when they use non-compatible information systems.) - Health Care Providers who transmit health information in electronic form in connection with one or more of the eight covered transactions. Business associates of a covered entity are not directly controlled by the regulations, but mandatory contracts require them to protect the privacy of individually identifiable information. Government agencies specifically named in the regulations are covered entities, as are agencies that function as a health plan or a health care provider. - Electronic Data Interchange (EDI) - Transaction Standards - Code Sets - National Standard Identifiers - Health Plan Electronic Data Interchange ( EDI ) These regulations are identified as the Transaction Code Set Standards. The final rules for EDI and Code sets were implemented on October 16, 2003. Several of the transaction regulation standards are still under review and have not been published. The purpose of these regulations is to standardize the electronic exchange of information (transactions) between trading partners. These transactions are mandated to be in the ANSI ASC X12 version 4010 format. The covered transactions include: - 270 = Eligibility Inquiry - 271 = Inquiry and Response - 276 = Claim Status Inquiry - 277 = Claim Status Inquiry and Response - 278 = Authorization Request and Authorization Response - 820 = Health Insurance Premium Payment - 834 = Beneficiary Enrollment - 835 = Remittance / Payment - 837 = Claim or Encounter The HIPAA Code Set Regulations establish a uniform standard of data elements used to document reasons why patients are seen and the procedures performed during health care encounters. HIPAA specified code sets to be used are: - Diagnoses - ICD 9 - Procedures - CPT 4, CDT - Supplies/Devices - HCPCS - Additional Clinical Data - Health Level Seven (HL7) HIPAA specified administrative codes set for use in conjunction with certain transactions and HIPAA eliminated state-specific local codes. These regulations establish standards for protecting individually identifiable health information and for guaranteeing the rights of individuals to have more control over such information. HIPAA privacy regulations were implemented on April 14, 2003. Privacy rules define the rights of individuals and security rules define the process and technology required to ensure privacy. These regulations establish standards for the security of electronic protected health information (PHI). HIPAA security regulations were implemented on April 21, 2005 for all but small health plans (who must comply by April 20, 2006). The final regulations adopt standards for the security of electronic protected health information (e-PHI). These standards are organized into the following three high level categories: - Administrative safeguards include policies, procedures, and practices that guide security management and information access authorization/revocation, contingency planning and training. These rules are enforced through sanctions and are largely directed toward the covered entity's workforce. - Physical safeguards include protections that minimize physical access to information within buildings, floors, departments, offices, and desks. These safeguards include doors, locks, badge access, location of workstations (obscured from public view), and media controls (e.g. location of back-up tapes). - Technical safeguards include limiting electronic information access to particular users or user groups, including different levels of software access rights, and tracking access through audit controls. National Provider Identifiers (NPI) These regulations establish the standard unique health identifier for health care providers to simplify administrative processes, such as referrals and billing, to improve accuracy of data, and reduce costs. The Final Rule was published January 23, 2004. Health Care providers began applying for NPIs on the effective date of the final rule, which was May 23, 2005. All health care providers are eligible to be assigned NPIs; health care providers who are covered entities must obtain and use NPIs. All HIPAA covered entities must use NPIs by the compliance dates: - May 23, 2007 for all but small health plans. - May 23, 2008 for small health plans. Penalties for Failure to Comply with HIPAA - The legislation carries heavy civil and criminal penalties for failure to comply.US DHHS Office for Civil Rights will enforce civil penalties that may include penalties from $100 per violation to $25,000 per calendar year.US Department of Justice will enforce criminal penalties which may include up to 10 years imprisonment and a $250,000 fine.	3	14	0	0	0	1	0.253574	1	1,069
Pathology medical billing services are a set of services that help medical providers to manage their billing process. These services include electronic systems and software responsible for collecting patient information from insurance companies. Moreover, the most important thing you need to know about pathology billing is that it is essential for your business’s success. Because it helps you collect money faster than other methods, such as paper or manual billing, can do so. In addition, the pathology field is constantly evolving to make things clear and straightforward for insurance and medical billing specialists. But regrettably, these intricate and constantly altering codes make it challenging for many healthcare service providers to bill independently or through an internal billing team. The smart move in this circumstance is to hire pathology billing professionals to handle the work for you. The medical billing for pathology is more complex than other specialties due to the complexity of the DX and CPT codes. Selecting the correct billing services provider is necessary to increase your revenue cycle and handle your specialized medical billing properly. So, read the blog to know what you should consider before hiring a good services company. What are Pathology billing services? These specialized medical billing services work with pathologists and other doctors who perform tests to diagnose and treat diseases. Moreover, these services specialize in collecting insurance payments for pathology tests. Qualitative and quantitative testing are both used in pathology. Quantitative tests measure the amount of a chemical in the body, while qualitative tests detect its existence. How much calcium, for instance, does your body contain? For hospital-based services, pathology billing has its standards that might get problematic. Regulations, payer obligations, hospital compliance, and other measures are occasionally outdated. Which tests are included in pathology billing? The tests that are included in pathology billing include: It initially establishes the presence of a drug (qualitative) before showing its concentration (quantitative). Each type of medication has a unique code that must be carefully entered during billing. There are varied pathological tests – Pathology is the area of medicine that investigates disease processes and the effects of drugs, chemicals, and other physical agents on tissues. Pathologists diagnose diseases by examining body tissues and fluids under a microscope. So, below are several different tests that come under it: - Microbiological tests determine the presence of microorganisms like hepatitis, giardia, HIV, or rubeola. Specific codes are given to each of them. - The diagnosis is tested and confirmed using molecular pathology procedures that examine antigens, genes, and a few biological processes. - The examination of human tissue is a part of surgical pathology. The levels that make up the surgical pathology codes cover a broad range of topics. The code groups are arranged according to the complexity and cost of the procedure. A higher level of code will be used for the more expensive or challenging method. So, when you hire a pathology billing company, they will do all the above tests. You should know the codes you will use when filing your claim. The codes categorize and identify tests, procedures, and other medical procedures. In addition, they help payers understand what was done during a visit or process so they can determine if they will cover it. Many different types of codes can be used in medical billing claims: - CPT (Current Procedural Terminology) is healthcare providers’ most widely accepted coding system worldwide. It contains detailed descriptions of each procedure and any associated equipment costs and facility fees that may be involved with performing said procedure/treatment on a patient at an institution like yours! - HCPCS (Healthcare Common Procedure Coding System) – Another widely-used coding system that provides more specific information about individual services performed by healthcare professionals such as nurses or physicians who work within hospitals/clinics across America today! Below are the pathology codes that billing companies use: Field Code Range Anatomic Pathology 88000 – 88099 Hematology and Coagulation 85002 – 85999 Clinical Pathology Consultation 80500 – 80502 Surgical Pathology 88300 – 88399 Urinalysis 81000 – 81099 Molecular Pathology 81200 – 81479 Drug Testing 80100 – 80104 Chemistry 82000 – 84999 Cytopathology 88104 – 88199 Microbiology 87001 – 87999 Here are the top ICD-10 codes for pathology coding – - ICD-10-CM Code K29.50 – Medical ailments related to gastritis - ICD-10-CM Code K20.8 – Medical diagnosis of the allergic inflammatory condition in the esophagus - ICD-10-CM Code N20.1 – Code for kidney stones - ICD-10-CM Code C50.911 – Code that helps specify Breast cancer in women EMR System in Pathology Billing An EMR system is software that hospitals to manage patient records, including their medical history. Many doctors also use it to bill their patients, and it can be an essential tool for the medical billing industry. EMR is also known as Electronic Health Record (EHR) system. The EMR system will help doctors to record all of their patient’s treatments in one place so that they don’t need to keep track of their treatment plans by hand or on paper. With this system, they can easily access information about any given patient through its online portal or mobile app, making it easier for everyone involved in the process. What can Medical billing services do for your pathology practice? Pathology medical billing services are essential for pathology practice. These billing services can help you save time and money, improve your business and increase revenue. Moreover, these services are a great way of increasing the number of patients who visit your office. They also allow you to collect more money by offering them services such as insurance claim forms, claim status updates, patient reviews, lab results, etc. You must understand all the different types of medical billing services available to make sure that they fit into your budget as well as meet all of your needs when it comes time for payment later on down the road when bills come due every month or quarter, depending on which plan. So, here are the benefits that you would get from hiring these services. Billing medical billing companies can be a perfect way to assist you in growing your practice. The benefits of medical billing include the following: - You have increased revenue and profitability. Medical billing allows you to charge for your services, so you can increase your revenue and get the most out of each patient visit or procedure. - Reduced costs. Using a billing company can decrease the amount of time spent on paperwork and other administrative tasks. So this would free up more time for patient care and results in lower costs overall. - Better customer service experience. When patients need to communicate with their doctors, they are more likely to have a positive experience, so if you use a reliable billing company instead of doing it themselves since there’s clarity about who is responsible for paying what bill. - Increased patient satisfaction rates. Patient satisfaction rates tend to go up when people know exactly how much it will cost them for their visit or procedure, so having this information available from your medical billing company helps ensure that everyone is on board with the plan from start to finish. - Services for Pathology Benefits Verification. Even though it’s important to verify each patient’s eligibility before submitting a claim, we always verify each patient’s eligibility and benefits when billing for pathology specialty claims. In order for us to act appropriately and promptly, our eligibility confirmation services team examines whether or not this patient plan covers treatments linked to pathology. We determine the patient obligations (including the copay, coinsurance, and deductible) following the benefits verification, and we update permission (if required). How can U Control Billing assist in billing services? U Control Billing is a medical billing company that provides billing services for pathologists. We have a team of experts who are well-versed in billing services, and they can help you with your billing services. We provide a variety of services that cover everything from telephonic billing to e-billing, invoicing, and more. Their team of experts knows how difficult it can be when there are issues with your billing process, so they can help you resolve any problems that may arise. They offer a variety of programs that can help physicians manage their accounts better than ever before. For example, they provide an online portal where physicians can upload their information into an electronic system and use it whenever needed. This helps them stay organized and makes it easier to keep track of everything related to their practice. Medical billing services Practice Management Services. Assisting you in finishing your activities quickly will enhance your workflow and increases your job efficiency. The committed team uses cutting-edge technology and current methods to help you complete your duties faster and with fewer resources. Using numerous methods, such as appointment scheduling, error elimination through automatic insurance eligibility checks, error notifications, and much more, direct and aid you in increasing your profits and revenue. Because of this, the team makes sure to reduce denials and boost your revenues. Assistance in making the right choice They specialize in making sensible financial and operational decisions while keeping you informed of the most recent changes that need to be made as soon as possible. Incorporating integrated dashboards guarantees quick performance, enabling reports to offer insightful analysis. Additionally, it is simple to integrate data into your decision-making thanks to the flexibility to examine standard reports or personally personalize them. Managing Pathology Denials For any healthcare service provider, claim denials can result in a significant loss. However, you can get excellent denial management from our pathology denials management staff. With their years of pathology billing knowledge, they are fully aware of MACRA and know what to do in the event of any potential denials that may arise while charging for pathology practices. Patient Information and Billing Services The demographics entry is crucial before creating a claim for any patient. To prevent denial or rejection, we ensure to include patient information by the patient data in the insurance system. In addition, our charge entry services team makes sure to enter the proper charges from superbill because the insurance bill relies on the amounts we bill. So, if you hand us the work you would not regret it. As our professionals always make sure to serve the clients in the best way. Assistance in making the right choice Our company makes sensible financial and operational decisions while keeping you informed of the most recent changes that need to be made as soon as possible. Incorporating integrated dashboards guarantees quick performance, enabling reports to offer insightful analysis. Additionally, it is simple to integrate data into your decision-making thanks to the flexibility to examine standard reports or personally personalize them. Guidelines for improved Pathology billing - Recognize which pathology services are billable under split billing and which are not. - By identifying and correcting billing code problems, pathology claims scrubbing lowers the number of refused or rejected claims. - Since patient demographics contain all of the client’s information and medical history, accuracy in filling them out is crucial. - To prevent delays, keep track of the claims that are generated and the collections that are handled. Take note of and follow up on the Aged Claims as well. - Using codes and modifiers properly is a crucial duty. Applying standard CPT, HCPCS procedure and supply codes, and ICD-CM diagnosis coding by CMS guidelines is vital. Now that you know what U Control Billing services are and how they can help you with your pathology practice, it’s time to start! We provide the best pathology medical billing services. Our billing and coding specialists are just a phone call away, and we’re here to help you any time of day. So, get in touch with us immediately to acquire answers to your questions about medical billing. A couple of years ago, I executed the effective plan of creating a Medical billing and Coding company named U Control Billing. The company aims to bring revolutionary advancements to foster medical billing and coding revenues. As an official member of HIA-LI and MGMA, I feel honored in providing networking opportunities, problem-solving, and improving the revenue management cycle.	3	20	2	0	0	2	0.323487	4	2,541
\|Page tools: Print Page Print All\| Mortality analysis primarily focuses on underlying causes of death. The underlying cause is the disease or condition which led directly to the death. These underlying causes are coded in accordance with the International Classification of Diseases – Version 10 (ICD-10). However, death certificates contain more information than just the underlying cause of death. The certificates also include significant diseases and/or conditions which led to or contributed to death (i.e. associated causes). Multiple cause of death statistics refer to both underlying and associated causes of death (see Causes of Death, Australia (cat. no. 3303.0) Glossary for further details). Multiple cause of death data have been compiled for Australia since 1997. Across the causes of death dataset, multiple cause data is particularly valuable in providing an insight into deaths which can be attributed to a number of concurrent disease processes. It enables the identification of patterns of association amongst conditions, links which may assist in targeting health interventions. This chapter focusses on multiple cause data for suicide deaths. From the outset, it is important to distinguish between the number of times a cause or group of causes appears on death records and the number of deaths where the cause (or group of causes) is mentioned. For example, if a death record contained three different codes from the range of codes belonging to Diseases of the circulatory system (I00-I99), then there are three causes (within the circulatory disease chapter), but only one death. Counts presented in this chapter reflect the number of suicide deaths where a particular multiple cause has been identified. Where more than one multiple cause has been identified for a particular death it may contribute to counts against more than one condition or group of conditions, but it will only contribute once to the total number of deaths. Care needs to be taken when analysing multiple cause of death data associated with suicide deaths. Data quality depends on the procedures being followed at every stage of collection and processing of statistical information. The quality of multiple cause of death data is particularly dependent on the contribution that doctors and coroners make when recording information about a death. When analysing multiple causes of death data, it is important to note that some conditions present at death will not be identified, effectively leading to under-reporting of associated causes and conditions. The extent to which under-reporting of multiple causes of death occurs is unknown and there may be differences in the likelihood of particular conditions being identified. Most suicide deaths are sudden or unexpected in nature. This, combined with a low median age at death, means that the likelihood of associated conditions being identified and recorded is also low. However, in some cases, mental health conditions, cancers or other terminal conditions may be viewed as a trigger or precursor to the suicide event. A secondary cause of death was recorded for only 22% of deaths from suicide between 2001 and 2010 compared to 96% for all deaths during the same period. The data presented in this chapter focuses only on the 22% of suicide deaths from 2001-2010 for which an associated cause was recorded. Care should be taken in making inferences about all suicide deaths based on this sub-group. SUICIDE DEATHS WITH MULTIPLE CAUSES Between 2001 and 2010, 22,526 deaths were registered where suicide was determined to be the underlying cause. Of these suicide deaths, 22% (4,932) were recorded with a multiple cause of death; that is, any condition, disease or injury which was involved in the morbid train of events leading to death (see Glossary for further details). This chapter focuses on data for these 4,932 suicide deaths with multiple causes recorded. Table 7.1 reports the number of suicide deaths by multiple cause by 10 year age groups. For instance, in Table 7.1, there were 340 suicide deaths of 15-24 year olds where the group of multiple causes Mental and behavioural disorders (F00-F99) was listed. The sub-categories of Mental and behavioural disorders (F00-F99) also include counts of suicide deaths. One death may be counted in more than one sub-category but can only contribute once at the broader level of the classification. Consequently, counts of suicide deaths at the sub-category level will add up to more than the total for this group of causes. The likelihood of a multiple cause of death being identified with a suicide increases with age. Only 19.6% of 15-24 year olds who died of suicide had a multiple cause identified, while this increased to 31.4% for individuals aged 75 years or older. It should be noted that this trend may reflect the tendency for a greater number of medical conditions to be present in advanced age. A Mental or behavioural disorder (F00-F99) was recorded for over half of all individuals who died from suicide and for whom a multiple cause was identified. The highest incidence of these disorders was observed in younger age groups: 58.6% of persons aged between 15 and 24 years and 61.6% of persons aged between 25 and 34 years. A Mental and behavioural disorder (F00-F99) was listed as a multiple causes for only 23.0% of individuals aged 75 years and over who died from suicide and for whom a multiple cause was identified. Within the category Mental and behavioural disorders (F00-F99), two disorders were most commonly associated with suicide: Mood disorders (F30-F39) and Mental and behavioural disorders due to psychoactive substance use (F10-F19). These disorders were also the most common Mental and behavioural disorders recorded with suicide across all age groups. Mood disorders (F30-39) were reported in 28.1% of all suicides where a multiple cause was identified, and occurred most often in suicides of 45-54 year olds (33.4%). Mental and behavioural disorders due to psychoactive substance use were recorded in 19.4% of all suicides where a multiple cause was identified, and were most prevalent for persons aged between 15 and 24 years and 25 and 34 years (30.0 and 30.2% of these age groups respectively). The prevalence of the main associated causes of death at the ICD-10 chapter level, for those suicide deaths where a multiple cause was identified, is shown in Figure 7.1. Footnote(s): (a) Includes ICD-10 codes X60-X84 and Y87.0. Care needs to be taken in interpreting figures relating to suicide. See Causes of Death, Australia, 2010 (cat. no. 3303.0) Explanatory Notes 98-101. (b) All causes of death data from 2006 onward are subject to a revisions process - once data for a reference year are 'final', they are no longer revised. Affected data in this graph are: 2006 (final) 2007 (final), 2008 (final), 2009 (revised), 2010 (preliminary). See Causes of Death, Australia, 2009 (cat. no. 3303.0) Technical Note and Explanatory Notes for further information. Source(s): Suicides, Australia All underlying causes with multiple causes of death Amongst all deaths where suicide was found to be the underlying cause, only 22% had an associated (multiple) cause of death, whereas for all underlying causes of death, 96% had associated causes. There were differences observed between the types of multiple causes of death associated with suicide and the multiple causes observed when all other underlying causes were considered. Table 7.3 presents the proportions of deaths with selected multiple causes for all underlying causes of death. For deaths due to any underlying cause, Diseases of the circulatory system (I00-I99, associated with 59.7% of deaths), Neoplasms (C00-D48, 35.0%) and Diseases of the respiratory system (J00-J99, 31.8%) were the most common diseases or conditions that contributed to death. Suicide deaths were most commonly associated with Mental and behavioural disorders (F00-F99, 50.2%), Diseases of the circulatory system (I00-I99, 19.4%), and Diseases of the respiratory system (J00-J99, 9.6%).	4	10	0	0	0	11	0.43013	11	1,680
The computer engineering geniuses at Apple have done it again. They’ve created yet another device that I’m probably going to have to buy. The new Apple Watch (series 4) has the ability for anyone to monitor their EKG (sort of). But what are we as physicians going to do with this data? Most electronic medical records permit patients to upload images to their patient portals for their physicians to have access to. Inevitably, some patients will overuse this system – some physicians are already drowning in dozens of Apple Watch rhythm strips being submitted by a single patient. But even for the patient who sends in a single suspicious rhythm strip, if the physician is going to make a clinical decision based on the strip, what are the implications? So, this presents several questions for physicians. What is it? The Apple Watch 4 can monitor the heart rhythm in two ways. First, it can measure the regularity of the heart beat by essentially taking the patient’s pulse; this can be reported as regular or irregular. Second, it can measure a single lead EKG reading and it is this latter feature that is really innovative. All EKGs are done by positioning 2 electrodes on different parts of the body and then measuring the electrical signal between those electrodes. A full EKG uses 12 electrodes and produces 12 different wave forms, or leads. The first three of these leads are the limb leads I – III. Lead I measures the signal between the left arm and right arm. Lead II is between the left leg and right arm. Lead III is between the left leg and left arm. The problem with a watch is that an electrode sensor on the back of the watch only has contact with one arm but by placing a second electrode sensor on the knob of the watch, a person can touch that second electrode with a finger from the other arm, thus generating a lead I EKG tracing by having an electrode in contact with both the left and the right arms simultaneously. What can it tell you? Since the Apple Watch can only generate a single lead EKG, there are limitations about the amount of information it can provide. For example, you cannot diagnose a myocardial infarction from only one lead (you need all 12). The main information that the lead I tracing will give you is whether the patient is in sinus rhythm or atrial fibrillation. Apple claims that the Apple Watch is 98.3% sensitive and 99.6% specific for classifying atrial fibrillation. However, 12.2% of rhythms could not be classified by the Apple Watch EKG app. Although Apple only mentions atrial fibrillation on its marketing materials for the Apple Watch 4, any physician who looks at telemetry monitor strips in the hospital knows that there are other important rhythm abnormalities that can be identified from a single lead EKG tracing. What should you do if the patient uploads a rhythm strip? Although we all get trained in EKG interpretation in medical school, most physicians are not credentialed to read 12-lead EKGs. In most hospitals, physicians must apply for hospital privileges to interpret EKGs and generally, this will be limited to cardiologists; in smaller hospitals, it may be a general internist who has EKG interpretation privileges. Reading an Apple Watch rhythm strip is considerably less complicated than reading a full 12-lead EKG but nevertheless, physicians should know their own limits as to whether they can confidently identify atrial fibrillation (or some other abnormal rhythm) by a rhythm strip. So, for example, if you are a podiatrist or dermatologist and do not normally look at heart rhythm strips, you may want to tell the patient who uploads an Apple Watch rhythm strip to your electronic medical record that EKG interpretation is not part of your normal practice and that they should check with one of their other physicians. However, most primary care physicians are trained in the recognition of atrial fibrillation. Can you bill for review of the rhythm strip? The short answer is in 2018, no but in 2019… maybe. Lets take a look at the CPT code possibilities for Apple Watch rhythm interpretation. - CPT code 93010 (Medicare reimbursement about $8.50). This is the CPT code for interpretation of a 12-lead EKG if someone else (usually the hospital) owns the EKG machine. It requires an order from a physician and a written interpretation. Since an Apple Watch rhythm strip is only 1 lead and since it is done by the patient’s initiation and not by the physician’s order, CPT 93010 cannot be used. - CPT code 93042 (Medicare reimbursement about $7.00). This is the CPT code for rhythm strip interpretation of 1-3 leads of EKG tracings. Like the previous CPT code, this requires an order from a physician and a written interpretation. Although it is conceivable that 93042 could be used to bill for Apple Watch rhythm strip interpretation, I would be hesitant to bill it since the patient is submitting the strip without a physician order. - CPT code G2010 (Medicare reimbursement about $6.50). This is the new CPT code for “Remote Evaluation of Pre-Recorded Patient Information” that was created as part of the 2019 Medicare physician fee schedule. This was designed for video or images such as photos of a rash, etc. that a patient creates and then sends to the physician for review. There are several restrictions when billing this CPT code, however. The physician doing the review of the pre-recorded information cannot have seen the patient for a regular evaluation & management encounter within the previous 7 days or within 24 after reviewing the images. Also, the physician has to interpret the image and communicate the findings to the patient within 24 business hours. We will not know for sure if Medicare carriers will accept CPT code G2010 for Apple Watch rhythm interpretation until the new fee schedule goes into effect after January 1, 2019 and we start submitting bills for it; however, it would seem like this CPT code would be the best fit. Who should get one? Since the main thing the Apple Watch EKG app does is tell whether there is atrial fibrillation, it will primarily be useful for patients at risk of atrial fibrillation or with a history of previous atrial fibrillation. Better identification of patients with intermittent atrial fibrillation really could save lives since about 15% of all strokes are the result of untreated atrial fibrillation. My suspicion is that a lot of other people with occasional PACs or PVC (premature atrial/ventricular contractions) will also be uploading rhythm strips to understand why they have occasional subjective “skipped heartbeats”. Although not designed for PAC or PVC identification, this could be a side benefit of the app. Similarly, ventricular arrhythmias such as non-sustained ventricular tachycardia may be identifiable. Bradycardic rhythms such as sinus bradycardia and various forms of heart block (1st degree, 2nd degree, and 3rd degree) may be identifiable. Even if these rhythms cannot be diagnosed with complete certainty, the tracings from the Apple Watch EKG app may be suspicious enough for the physician to direct the patient to seek medical attention where a full 12-lead EKG or a 24-Holter monitor can be performed. I’ve never had atrial fibrillation or any kind of heart problem. So, am I going to get an Apple Watch 4 with an EKG app… well, yeah, probably. December 20, 2018	4	9	8	0	4	0	0.613882	12	1,592
\|Integrative Therapy Quick Links:\| - Amyloidosis, arrhythmia, arrhythmogenic right ventricular cardiomyopathy, arrhythmogenic right ventricular dysplasia, ARVC, ARVD, broken heart syndrome, CAD, cardiac resynchronization therapy, congestive heart failure, coronary artery disease, CRT, dilated cardiomyopathy, diuresis, endomyocardial fibrosis, familial hypertrophic cardiomyopathy, HCM, heart disease, heart failure, hypertrophic cardiomyopathy, ICD, implantable cardioverter-defibrillator, ischemic cardiomyopathy, myocardium, peripartum cardiomyopathy, postnatal cardiomyopathy, pregnancy-induced hypertension (preeclampsia), primary cardiomyopathy, restrictive cardiomyopathy, sarcoidosis, secondary cardiomyopathy, stress cardiomyopathy. - Cardiomyopathy refers to several diseases that affect the myocardium (heart muscle) and are associated with mechanical and/or electrical dysfunction. In cardiomyopathy, abnormal heart function results from weakness or structural changes in the myocardium. - There are four main types of cardiomyopathy as defined by the American Heart Association (AHA): arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy, and restrictive cardiomyopathy. They are then categorized into two groups: primary or secondary. Primary cardiomyopathies may be genetic (inherited) or acquired (develop the condition). Secondary cardiomyopathies result from an underlying condition such as diabetes, thyroid disorders, chronic alcohol consumption, infection, or drugs/toxins (e.g., heavy metals, anthracyclines, cocaine). Clinical presentation varies from asymptomatic (without symptoms) to sudden cardiac death. - Therapies for cardiomyopathy aim to reduce the symptoms of heart failure and the risk of complications such as arrhythmia (irregular heartbeat or abnormal heart rhythm). Treatments may involve drugs, implantable cardioverter-defibrillators (ICDs), or cardiac resynchronization therapy (CRT) to regulate the heartbeat and reduce the risk of fatal arrhythmias. In some cases, heart transplant may be necessary. General measures that may reduce mortality and prevent future occurrences of heart failure include controlling blood pressure and weight (through diet and exercise), reducing alcohol and sodium consumption, and quitting smoking. Signs and symptoms - General: The symptoms of cardiomyopathy are similar to the symptoms commonly seen in heart failure, particularly congestion (backed up blood) caused by abnormal heart function. The symptoms of congestion include shortness of breath, fatigue, and swelling, particularly in the legs and feet. Other symptoms such as dizziness, lightheadedness, and fainting develop as the body tries to compensate for the heart's reduced pumping ability. As the heart beats faster, its muscle thickens, and the ventricles (pumping chamber) may stretch to accommodate more blood. Damage to the ventricles may cause them to pump irregularly, further reducing the efficient delivery of blood to the body. - Symptoms of congestive heart failure (CHF, a condition in which the heart cannot pump enough blood to meet the body's needs) include: a dry, hacking cough, especially when lying down; confusion, sleepiness, and disorientation may occur in older individuals; dizziness, fainting, fatigue, or weakness; fluid buildup (edema), especially in the legs, ankles, and feet; increased urination at night; nausea; abdominal swelling, tenderness, or pain; weight gain due to fluid buildup; weight loss as nausea causes a loss of appetite and as the body fails to absorb food well; rapid breathing, bluish skin, and feelings of restlessness, anxiety, and suffocation; shortness of breath and lung congestion as the blood backs up in the lungs; and wheezing and spasms of the airways similar to asthma. - In arrhythmogenic right ventricular cardiomyopathy (ARVC), symptoms of heart failure are less common than other forms of cardiomyopathy. Instead, tachycardia (fast heartbeat) and angina (chest pain) are typical symptoms. - Many cardiomyopathies present no obvious symptoms in early stages. Sometimes, sudden heart failure and/or death are the first symptoms of cardiomyopathy. - General: Because the most common symptom of cardiomyopathy is heart failure, diagnosis of cardiomyopathy follows similar guidelines for evaluating heart failure. Physical examination, blood tests, electrocardiogram (ECG or EKG), echocardiogram, chest X-ray, magnetic resonance imaging (MRI), cardiac catheterization, stress test, and nuclear stress test are used to diagnose cardiomyopathy. These tests may also reveal structural defects in the heart muscle (myocardium) that are characteristic of cardiomyopathy. - Physical examination and medical history: During a physical examination, a doctor will look for underlying causes of the problem and assess heart function. A stethoscope is used to detect murmurs (abnormal heart sounds) that may indicate a leaky or narrowed valve and to detect fluid accumulation in the lungs. The doctor also looks for enlarged veins in the neck and for edema (swelling) in the legs, particularly the ankles, feet, and/or the abdomen. - A patient history may include information about risk factors, such as family medical history, past surgeries and medications, history of chest pain, high blood pressure (including treatments), heart attack, recent viral illness, or recent pregnancy. - Blood tests: Blood tests may include: blood cell counts to test for conditions such as anemia (low red blood cells); electrolyte levels, including sodium, potassium, and calcium; nutrient levels, such as vitamins and trace minerals; tests for kidney function, including blood urea nitrogen (BUN) and creatinine levels; and testing for homocysteine and/or C-reactive protein (CRP), both markers of inflammation and heart disease. Brain natriuretic peptide (BNP) is a test used to measure the amount of BNP hormone in the blood and also used to diagnose heart failure. Brain natriuretic peptide (BNP) is a hormone produced at higher levels by the failing heart muscle. - Electrocardiogram (ECG or EKG): An electrocardiogram (ECG or EKG) is a noninvasive test used to measure electrical activity in the heart. Electrical sensors called leads are attached to predetermined positions on the arms, legs, and chest to record electrical activity and help assess heart function. The heart's rhythm of contraction is controlled by the sinoatrial node (SA node), often called the pacemaker. Electrical impulses generated from the SA node spread through the heart via a nodal tissue pathway that coordinates the events leading to heart beat. This conduction system initiates and coordinates the muscular activity of the heart. - Echocardiogram: An echocardiogram, or echo, is an ultrasound examination of the heart that produces detailed images of the organ. It may be used to detect abnormalities in the structure of the heart and to measure the amount of blood ejected from the heart. During an echocardiogram, a microphone-like device (transducer) is used to transmit and receive ultrasonic waves that travel through the chest wall to the heart and are reflected back to the transducer. The reflected sound waves are translated into images of the heart, including the valves, chambers, and walls. - Echocardiogram also is used to measure the pressure change (gradient) between the left ventricle and the aorta (largest artery of the body), to assess thickening of the walls of the heart, to evaluate pumping function, and to measure the amount of dilation (increased diameter) of the left ventricle. - Chest X-ray, magnetic resonance imaging (MRI), or computerized tomography (CT) scan: X-rays, MRIs, and CT scans are useful in visualizing structural defects in the heart that cause cardiomyopathy. These defects include enlargement of the heart or thickening of the myocardium. - Cardiac catheterization: Cardiac catheterization may be performed in individuals with angina and in those with a history of heart attack to determine if coronary heart disease (CHD) is causing heart failure. Cardiac catheterization with angiograms (x-ray images of blood vessels) of the coronary arteries and the left ventricle can be used to monitor heart function. - Cardiac catheterization involves injecting a small amount of radioactive dye, called a contrast agent, into the left ventricle through a catheter (a thin flexible tube). A special camera is then used to determine how much of the dye is ejected from the heart with each beat. The infusion of dye typically produces a characteristic "hot flash" sensation throughout the body that lasts 10-15 seconds. - Stress test: In some individuals, a less invasive procedure called a stress test is used to assess the possibility of coronary heart disease (CAD). If the results of this procedure suggest the presence of CAD, a subsequent referral for cardiac catheterization is likely. - Several types of stress tests may be used by doctors to access heart function. In some cases, the individual simply walks on a treadmill while connected to an ECG. Another type uses intravenous (IV, or in the veins) medication, usually a platelet inhibitor like dipyridamole (Persantine®), which reproduces the stress of exercise on the heart. - Nuclear stress test: Nuclear stress tests involve injecting a radioactive substance, most commonly technetium or Tc-99m sestamibi (Cardiolite®), into a vein. A special camera (gamma camera) is then used to obtain images of the heart during rest and immediately following exercise on a treadmill as the radioactivity flows through the heart. The radioactivity levels used are not harmful. - A nuclear test called a radionuclide ventriculography or multiple gated acquisition (MUGA) scanning allows doctors to see how much blood the heart pumps with each beat, also known as the ejection fraction. The MUGA scan gives an accurate and reproducible means of measuring and monitoring the actual amount of blood ejected from the heart. The tests use a small amount of radioactive material injected into the veins. A special camera detects the radioactive material as it flows through the heart. - Individuals with an allergy to iodine or shellfish have special considerations and may not be able to have this test because the dye contains iodine. The use of medications, including the antihistamine diphenhydramine (Benadryl®) and/or prednisone (Deltasone®), prior to the administration of the dyes (contrast media), may help to prevent or decrease the chance of an allergic reaction. - Classifying heart failure: Results of these tests help doctors determine the cause of CHF and develop a program to treat the heart. To determine the best course of treatment, doctors may classify heart failure using one of two scales. The New York Heart Association scale classifies heart failure in categories from one to four. In class I heart failure, the mildest form, individuals can perform everyday activities and not feel winded or fatigued. Individuals with class II have slight limitation of physical activity and ordinary physical activity may result in fatigue, palpitation (pounding or racing), shortness of breath, or chest pain. Those with class III have marked limitation of physical activity and less than ordinary activity causes fatigue, palpitation, shortness of breath, or chest pain. Class IV is the most severe, and individuals have shortness of breath even at rest. - The American College of Cardiology scale uses letters A-D. The system includes a category for individuals who are at risk of developing heart failure. Early stage heart failure includes stage A (individuals are at risk for developing heart failure without evidence of heart dysfunction) and stage B (there is evidence of heart dysfunction without symptoms). Advanced stage heart failure includes stage C (there is evidence of heart dysfunction with symptoms) and stage D (there are symptoms of heart failure despite maximal therapy). Doctors can use these classifications to identify the risk factors and begin early, more aggressive treatment to help prevent or delay heart failure. - The most common complication of most types of cardiomyopathy (dilated, hypertrophic, and restrictive) is heart failure, which may be fatal. Arrhythmias (abnormal heartbeats) and angina (chest pain) may also occur, especially in arrhythmogenic right ventricular cardiomyopathy (ARVC) in which heart failure is less common. - Treatment for cardiomyopathy aims at treating heart failure. This involves reducing symptoms, treating the underlying cause of the condition when possible, and using medications to prevent further deterioration of heart function. For arrhythmogenic right ventricular cardiomyopathy (ARVC), in which heart failure is less common, treatment is directed at preventing arrhythmia (irregular heartbeat). - Lifestyle changes: - Lifestyle changes may help reduce symptoms such as fatigue, shortness of breath, and edema (swelling). These modifications may include dietary changes (such as a restricted salt intake of less than 2,000 milligrams daily), abstaining from alcohol, smoking cessation, and exercising regularly (under the supervision of a doctor). - A combination of medications is used to treat congestive heart failure (CHF). Depending on the symptoms, individuals with CHF may take one, two, or more of these drugs. Several types of medications have proved useful in the treatment of heart failure including: angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, digoxin, diuretics, and aldosterone antagonists. - Angiotensin-converting enzyme (ACE) inhibitors: Angiotensin-converting enzyme (ACE) inhibitors are medications that dilate or widen blood vessels to lower blood pressure, improve blood flow, and decrease the workload on the heart. Some examples of ACE inhibitors include enalapril (Vasotec®), lisinopril (Prinivil®, Zestril®), and captopril (Capoten®). - Side effects of ACE inhibitors include chronic, nonproductive cough (occurs in about 10% of patients), dizziness or weakness (caused by low blood pressure), increased potassium levels, skin rashes, and angioedema (sudden swelling of the lips, face, and cheeks; if this occurs, the patient must seek medical attention immediately). - Angiotensin II (A-II) receptor blockers (ARBs): Angiotensin receptor blockers, or ARBs, have many of the beneficial effects of ACE inhibitors, but they do not cause a persistent cough. They may be an alternative for individuals who cannot tolerate ACE inhibitors. Some examples of ARBs include losartan (Cozaar®) and valsartan (Diovan®). - Digoxin (Lanoxin®): Digoxin (Lanoxin®) increases the strength of the heart muscle contractions. Digoxin also tends to slow the heartbeat. Digoxin reduces heart failure symptoms and improves the individual's ability to live with CHF. Side effects may include blurred vision, cardiac problems (such as irregular heartbeat or heart block), diarrhea, headaches, loss of appetite, hypotension (low blood pressure), and nausea and vomiting. Rarely, digoxin may cause a disturbance of color (typically yellow and green) and halos around light. Most side effects are dose-dependent and occur when blood levels of the drug are more than the therapeutic range. - Beta-blockers: Beta-blockers are a class of drugs that slows the heart rate and reduces blood pressure. Some examples include carvedilol (Coreg®), metoprolol (Lopressor®), and propranolol (Inderal®). These medicines also reduce the risk of some abnormal heart rhythms. Beta-blockers may reduce signs and symptoms of heart failure and improve heart function. Beta-blockers are started at low doses that are gradually increased over a period of several months. During the first several weeks of treatment, some patients experience worsening symptoms, due to a decrease in oxygen circulation in the body. Other side effects include low blood pressure, difficulty breathing, sexual dysfunction, nausea, and weakness with exertion. - Diuretics: Diuretics or water pills decrease the amount of fluid in the body typically by increasing the rate of urination. Commonly prescribed diuretics for heart failure include hydrochlorothiazide (Diuril®) and furosemide (Lasix®). Diuretics also decrease fluid in the lungs, helping individuals breathe more easily. Common side effects include frequent urination and low potassium blood levels (hypokalemia) or high potassium levels (hyperkalemia), depending on the diuretic. Because of this, blood tests are performed periodically and a potassium supplement is prescribed if blood levels are low. Individuals may be asked to eat more fruits high in potassium, such as bananas and oranges, while on diuretic therapy. Other side effects include low sodium levels (hyponatremia), increased blood sugar (hyperglycemia), increased cholesterol (hyperlipidemia), rash, joint disorders (e.g., gout), impotence (men), menstrual irregularities (women), and breast enlargement in men. - Aldosterone antagonists: Aldosterone antagonists are primarily potassium-sparing diuretics, but they have additional properties that help the heart work better, may reverse scarring of the heart, and may help individuals with severe heart failure live longer. Aldosterone antagonists include spironolactone (Aldactone®) and eplerenone (Inspra®). Unlike other diuretics, spironolactone can raise the level of potassium in the blood to dangerous levels. Healthcare professionals recommend eliminating high-potassium foods, such as bananas, lentils, nuts, peaches, potatoes, salmon, tomatoes, and watermelon while taking aldosterone antagonists. - Others: A medication called BiDil® is a single pill that combines hydralazine and isosorbide dinitrate, both of which dilate and relax the blood vessels. BiDil® increases survival when added to standard therapy in African American individuals with advanced heart failure. This is the first drug studied and approved for a specific racial group following the results of a human trial that found the medication reduced death, hospitalizations, and symptoms of heart failure among black patients who tried other agents. Further studies will be necessary to determine if this combination medicine will be helpful for others with heart failure. Side effects may include blurred vision, dry mouth, irregular heartbeat, blood in the urine or stools, numbness or tingling in the arms or legs, and fainting. - Doctors often prescribe other medications such as HMG-CoA reductase inhibitors (statin) drugs for cholesterol reduction. Some examples are atorvastatin (Lipitor®) and lovastatin (Mevacor®). They may cause liver problems or muscle pain. Anti-arrhythmic drugs may also be prescribed to control irregular heartbeats, including diltiazem (Cardizem®, Cardizem CR®) and verapamil (Calan®, Calan SR®). - Individuals may be hospitalized for a few days if complications arise as a result of CHF symptoms. While in the hospital, individuals may receive additional medications such as intravenous (IV, or into the veins) dobutamine (Dobutrex®), milrinone, (Primacor®), and nitroglycerin. These drugs work quickly to help the heart pump better and relieve symptoms. Individuals may also receive supplemental oxygen through a mask or small tubes placed in the nose. If severe heart failure is present, the individual may need to use supplemental oxygen long term. - Individuals hospitalized with severe CHF may be given an intravenous drug called nesiritide (Natrecor®). Nesiritide is a synthetic version of a naturally occurring hormone in the body called brain natriuretic peptide (BNP). BNP is secreted in high levels by the heart in response to a failing heart. However, it is not clear if nesiritide is better than other intravenous medications for severe heart failure. Studies are ongoing to evaluate the safety and effectiveness of nesiritide in heart failure. - Other treatments: - Aquapheresis: In some cases, heart failure persists or worsens in spite of treatment. An ultrafiltration process called aquapheresis, which uses a mechanical system called the Aquadex FlexFlowT, may be used to remove excess fluids and salt in CHF individuals who do not respond to lifestyle modifications and medication. In this treatment, blood is withdrawn using catheters (small tubes) inserted into veins in the arm, leg, or neck. The blood is then passed through a filter that removes excess fluid and is returned to the body. Studies have reported that ultrafiltration can remove more fluid at a faster rate than medication. The length of each treatment depends on the rate at which fluid can be removed from the body and the amount that must be removed. Low blood pressure (hypotension) may occur. - Angioplasty: CHF caused by reduced blood flow in the heart as a result of blockages (plaques) in one or more coronary arteries may be treated using coronary angioplasty. In this procedure, a hollow tube (catheter) is inserted through an artery (usually the femoral artery in the groin), into the coronary artery, and to the blockage. A small balloon is then inserted through the catheter and is inflated to open the blocked artery. There is a slight risk for damage to the artery during angioplasty, but heart failure symptoms usually improve following the procedure. Stenting is used along with balloon angioplasty. Stenting involves placing a mesh-like metal device into an artery at a site narrowed by plaque. The stent is mounted on a balloon-tipped catheter, threaded through an artery, and positioned at the blockage. The balloon is then inflated, opening the stent. Then the catheter and deflated balloon are removed, leaving the stent in place. The opened stent keeps the vessel open and stops the artery from collapsing. Re-closure may occur with both balloon angioplasty and stenting. Doctors may prescribe blood thinning medications to help keep the arteries open, including aspirin, warfarin (Coumadin®), and clopidogrel (Plavix®). - Coronary artery bypass graft surgery (CABG): A coronary artery bypass surgery (CABG) may be recommended if the individual has severe coronary artery disease (CAD) in addition to CHF. This may improve the blood supply to the heart. CABG surgery uses blood vessel grafts, which usually come from the patient's own arteries and veins located in the chest, leg, or arm. The graft goes around the clogged artery to create new pathways for oxygen-rich blood to flow to the heart. Some problems associated with CABG include a heart attack (occurs in five percent of patients), stroke (occurs in five percent, with the risk greatest in those more than 70 years old), blood clots, death (occurs in 1-2% of individuals), and wound infection (occurs in 1-4%). Infection is most often associated with obesity, diabetes, or having had a previous CABG. In about 30% of patients, post-pericardiotomy syndrome may occur anywhere from a few days to six months after surgery. The symptoms of this syndrome are fever and chest pain. Symptoms may be treated with medications, including antibiotics (for infection), nitroglycerin, and anti-inflammatory drugs. The incision in the chest or the graft site (if the graft was from the leg or arm) may be itchy, sore, numb, or bruised. Some individuals report memory loss, loss of mental clarity, or "fuzzy thinking" following a CABG. - Implantable cardiac defibrillator (ICD): An implantable cardiac defibrillator (ICD) may be used to treat severe heart failure. An ICD is a small electronic device that is surgically implanted under the skin in the chest to monitor heart rhythm. When an abnormal rhythm is detected, the defibrillator delivers an electrical shock to the heart to restore normal heart rhythm. - Intra-aortic balloon pump (IABP): An intra-aortic balloon pump (IABP) is a device that is inserted through an artery in the groin (femoral artery) and then placed within the main artery (aorta). An IABP is an inflatable balloon that expands and deflates in coordination with each heartbeat. It can be left in place for days to weeks, and decreases the strain on the heart and increases blood flow throughout the body. - Valve replacement surgery: Individuals with heart failure caused by an abnormal heart valve may require valve repair or valve replacement surgery. These are open-heart procedures in which an abnormal valve is repaired or replaced with a porcine valve (from pig tissue), a mechanical valve (made of synthetic material), or a homograft valve (from a human donor). Complications include bleeding, blood clots, infection, kidney failure, stroke, heart attack, valve rejection, and death. A homograft valve is preferred, as these valves are not associated with a significant risk for blood clot formation and, thus, do not require blood thinner therapy. Most individuals remain in the hospital for a week after surgery, and recovery takes approximately 3-4 weeks, after which most patients may resume leisure activities and many return to work. Approximately 60% of individuals who have valve replacement have a 10-year post-surgery survival rate. - Left ventricular assist device: A left ventricular assist device (LVAD) is a mechanical pump that is surgically implanted in the upper abdomen to bypass the left ventricle and pump blood throughout the body. This device may be used in patients with end-stage heart failure who are awaiting heart transplantation. Long-term use of the device in patients with severe heart failure is being explored and has not yet been defined. - Pacemaker: If individuals with CHF experience abnormal heart rhythms that will not respond to medication therapy, the irregular heart rhythms may be corrected with a pacemaker. A pacemaker is a small, battery-powered device that is usually implanted near the collarbone. Pacemakers can be surgically placed into the chest (a permanent pacemaker) through a small incision, or they can be worn outside the body (a temporary pacemaker) and attached to the heart through a wire that is threaded through a neck vein. Temporary pacemakers are used only while an individual is in the hospital. - The surgery needed to implant a permanent pacemaker is considered a minor surgical procedure. The procedure may take 1-2 hours to complete. The area where the pacemaker will be inserted will be numbed with an injection of an anesthetic such as lidocaine (Xylocaine®). The individual should not feel any pain during the procedure, and should inform the doctor or staff if he or she is having pain so that more anesthetic medication may be given. One or more electrode-tipped wires run from the pacemaker through the blood vessels to the inner heart. If the heart rate is too slow or if it stops, the pacemaker sends out electrical impulses that stimulate the heart to beat at a steady, proper rate. The more advanced pacemakers can monitor and pace either the atria or ventricles (or both) in proper sequence to maximize the amount of blood being pumped from the heart. The pacemaker's batteries may need to be changed every 5-10 years. It is recommended by the American Heart Association (AHA) to limit exposure to devices that may interfere with pulse generators such as cellular phones, CB radios, electric blankets, and microwaves. - It is normal for the surgical wound to be somewhat painful and swollen for a few days after the procedure. This can usually be controlled with medications, such as tramadol (Ultram®) or ibuprofen (Motrin®). The wound may also appear mildly red for a few days; however, if the area of redness enlarges, a doctor should be notified due to the potential for a serious infection. If there are no other problems, most individuals who have a permanent pacemaker surgically implanted can go home the next day. They may usually return to normal activities within six weeks. For several weeks after having a pacemaker implanted, the individual may be asked not to lift more than five pounds or raise the affected arm over their shoulder. - Heart transplant: In some cases, despite the use of optimal therapies, the individual's condition continues to deteriorate, due to progressive CHF. In selected individuals, heart transplantation is a viable treatment option. Candidates for a heart transplant are generally younger than age 70, do not smoke, and do not have severe or irreversible diseases affecting the other organs. Additionally, a transplant is done only when it is clear that the individual's prognosis (expected outcome) on the continued medical treatment is poor. Transplant patients require close medical follow-up while taking needed drugs that suppress the immune system because of the risk of rejection of the transplanted heart. They are even monitored for possible development of CAD in the transplanted heart. - Although there are thousands of patients on waiting lists for a heart transplant at any given time, the number of operations performed each year is limited by the number of available donor organs. For these reasons, heart transplantation is a realistic option in only a small subset of the large numbers of patients with CHF. - Strong scientific evidence: - Hawthorn: Hawthorn (Crataegus spp.), a flowering shrub of the rose family has an extensive history of use in cardiovascular disease dating back to the 1st Century. Increased blood flow to the heart and heart performance has been observed in animals when given hawthorn supplements. Extracts of the leaves and flowers of hawthorn have been reported as effective in the treatment of mild-to-moderate congestive heart failure (CHF), improving exercise capacity and reducing symptoms of cardiac insufficiency. However, whether hawthorn is as effective as drugs considered standard-of-care for heart failure (such as angiotensin converting enzyme (ACE) inhibitors, diuretics, or beta-adrenergic receptor blockers) is unclear, as is the effect of the combined use of hawthorn with these drugs. Nonetheless, hawthorn is a potentially beneficial treatment for patients who cannot or will not take prescription drugs and may offer additive benefits to established therapies. Further study is warranted. - Avoid if allergic to hawthorn or to members of the Crataegus species. Avoid with a history of low blood pressure, irregular heartbeat, asthma, low blood pressure when standing, or insomnia. Use cautiously in elderly patients. Avoid if pregnant or breastfeeding. - Good scientific evidence: - Arginine: Studies of arginine in patients with chronic heart failure (CHF) have shown mixed results. Some studies report improved exercise tolerance. Additional studies are needed to confirm these findings. - Avoid if allergic to arginine, or with a history of stroke, or liver or kidney disease. Avoid if pregnant or breastfeeding. Use caution if taking blood-thinning drugs (like warfarin or Coumadin®) and blood pressure drugs or herbs or supplements with similar effects. Blood potassium levels should be monitored as arginine may increase potassium levels. L-arginine may worsen symptoms of sickle cell disease. Caution is advised in patients taking prescription drugs to control blood sugar levels. - Berberine: Berberine is a bitter-tasting, yellow, plant alkaloid with a long history of medicinal use in Chinese and Ayurvedic medicine. Berberine is present in the roots, rhizomes, and stem bark of various plants including Hydrastis canadensis (goldenseal), Coptis chinensis (coptis or goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric). Preliminary clinical research suggests that berberine, in addition to a standard prescription drug regimen for chronic CHF, may improve quality of life, heart function, and risk of mortality. Further research is necessary. - Berberine has been reported to cause nausea, vomiting, hypertension (high blood pressure), respiratory failure, and paresthesias (abnormal sensations such as numbness or tingling). Use cautiously in patients with diabetes. Avoid if allergic or hypersensitive to berberine, to plants that contain berberine [Hydrastis canadensis (goldenseal), Coptis chinensis (coptis or goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric)], or to members of the Berberidaceae family. Avoid in newborns due to potential for increase in free bilirubin, jaundice, and development of kernicterus (a type of brain damage). Use cautiously with cardiovascular disease, gastrointestinal disorders, hematologic disorders, leucopenia, kidney disease, liver disease, respiratory disorders, cancer, hypertyraminemia, diabetes, or hypotension (low blood pressure). Use cautiously in children, due to lack of safety information. Use cautiously in individuals with high exposure to sunlight or artificial light. Use cautiously for longer than eight weeks, due to theoretical changes in bacterial gut flora. Use cautiously if taking anticoagulants, antihypertensives, sedatives, anti-inflammatories, medications metabolized by CYP P450 3A4 including cyclosporin, or any prescription medications. Avoid if pregnant or breastfeeding. - Coleus: Coleus species have been used in Asian traditional medicine for several indications. Since the 1970s, research was predominantly concentrated on forskolin, a root extract of Coleus forskohlii. A small number of studies suggest that forskolin may improve cardiovascular function in patients with cardiomyopathy. However, these trials are small and of poor quality. Larger studies are needed. - Coleus is generally regarded as safe, although long-term safety data are lacking. Avoid with a known allergy or hypersensitivity to Coleus forskohlii and related species. Rash may occur in sensitive individuals. Inhalation of forskolin may cause sore throat, upper respiratory tract irritation, mild-to-moderate cough, tremor, or restlessness. Coleus eye drops may produce a milky covering over the eyes. Use cautiously in patients with heart disease, asthma, thyroid disorders, diabetes, a history of bleeding, hemostatic disorders or drug-related hemostatic problems, low blood pressure, or in patients at risk for low blood pressure. Discontinue use in patients at least two weeks prior to surgical or dental procedures, due to risk of bleeding. Avoid in patients with active bleeding. Avoid during pregnancy. - Creatine: Creatine is naturally synthesized in the human body from amino acids primarily in the kidney and liver, and transported in the blood for use by muscles. Cardiac creatine levels have been reported as depressed in patients with chronic CHF. Several studies report that creatine supplementation is associated with improved heart muscle strength, body weight, and endurance in patients with heart failure. However, it is not clear what dose may be safe or effective. Supplementation is also reported to increase creatine in the skeletal muscle in these patients, helping to increase strength and endurance. Well-designed studies comparing creatine with drugs used to treat heart failure are needed. - Avoid if allergic to creatine or with diuretics (such as hydrochlorothiazide, furosemide (Lasix®)). Use caution in asthma, diabetes, gout, kidney, liver, or muscle problems, stroke or a history of these conditions. Avoid dehydration. Avoid if pregnant or breastfeeding. - Selenium: Keshan disease is a cardiomyopathy (heart disease) restricted to areas of China in people having an extremely low selenium status. Prophylactic administration of sodium selenite has been shown to significantly decrease the incidence of this disorder. Organic forms of selenium (such as selenized yeast or Se-yeast) may have better bioavailability than selenite and thus may be better preventative treatments for Keshan disease. Selenium is used to treat and prevent selenium deficiency (for example in those with HIV or receiving enteral feedings). - Selenium is a trace element and hypersensitivity is unlikely. Avoid individuals with a known allergy/hypersensitivity to products containing selenium. - The level of selenium exposure that will cause chronic toxicity is not known. Selenium toxicity may cause gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea, garlic-like breath odor, and metallic taste), neuromuscular-psychiatric disturbances (weakness/fatigue, lightheadedness, irritability, hyperreflexia, muscle tenderness, tremor, and peripheral neuropathy), dermatologic changes (skin rash/dermatitis/flushing, fingernail loss/thickening/blotching/streaking/paronychia, and hair changes/loss), liver dysfunction, kidney dysfunction, thrombocytopenia (low blood platelets), immune alterations (natural killer cell impairment), thyroid dysfunction (decreased T3), reduced sperm motility, or growth retardation. - Unclear or conflicting scientific evidence: - Aconite: The toxic effects associated with aconite limit its ability to be used to treat heart failure, including reno-cardiovascular disease and left ventricular function. Further study is needed. - Aconite is highly toxic and is not safe for human consumption. Avoid with heart disease, heart dysfunction, irregular heartbeat, hemodynamic instability (abnormal blood flow), gastrointestinal disorders, ulcers, reflux esophagitis, ulcerative colitis, spastic colitis, and diverticulosis. Use caution with diabetes and suicidal tendencies. Avoid if younger than 18 years. Avoid if pregnant or breastfeeding. - Astragalus: Astragalus (Astragalus membranaceus) is used in combination with other herbs in Chinese medicine to treat various heart diseases. There is some evidence that astragalus may offer symptomatic improvement for chronic heart failure. Recommendations cannot be made until well-designed clinical trials have been conducted. - Avoid if allergic to astragalus, peas, or any related plants or with a history of Quillaja bark-induced asthma. Avoid with aspirin or aspirin products or herbs or supplements with similar effects. Avoid with inflammation (swelling) or fever, stroke, transplant or autoimmune diseases (such as HIV/AIDS or human immunodeficiency virus/acquired immunodeficiency syndrome). Stop use two weeks before surgery/dental/diagnostic procedures with a risk of bleeding and avoid use immediately after these procedures. Use cautiously with bleeding disorders, diabetes, high blood pressure, lipid disorders, or kidney disorders. Use cautiously with blood-thinners, blood sugar drugs, or diuretics, or herbs and supplements with similar effects. Avoid if pregnant or breastfeeding. - Ayurveda: Ayurveda, which originated in ancient India more than 5,000 years ago, is probably the world's oldest system of natural medicine. Preliminary evidence suggests that sodium nimbidinate, made from the traditional Ayurvedic herb Nimba/Neem/Arishta (Azadirachta indica), may be an effective diuretic in patients with congestive heart failure (CHF). More studies are needed to confirm this effect. - Ayurvedic herbs should be used cautiously because they are potent and some constituents may be potentially toxic if taken in large amounts or for a long time. Some herbs imported from India have been reported to contain high levels of toxic metals. Ayurvedic herbs may interact with other herbs, foods, and drugs. A qualified healthcare professional should be consulted before taking. - Camphor: Preliminary evidence indicates that a German combination product of camphor and extract of hawthorn berries (Korodin® Herz-Kreislauf-Tropfen) may reduce overall symptoms in patients with functional cardiovascular disease. While these early findings are promising, further research is required before any recommendation can be made. - Camphor and camphor-containing products are generally applied as topical formulations. Ingestion of such preparations is not recommended, as they are potentially poisonous and may induce a number of adverse and potentially fatal side effects. Caution is advised for use of any internal preparations of camphor due to their potential toxicity. - Coenzyme Q10 (CoQ10): CoQ10 is produced by the human body and is necessary for the basic functioning of cells. The evidence for CoQ10 in the treatment of heart failure is controversial and remains unclear. Different levels of disease severity have been studied (New York Heart Association classes I through IV). Better research is needed in this area, studying effects on quality of life, hospitalization, and death rates. There is also conflicting evidence from research on the use of CoQ10 in patients with dilated or hypertrophic cardiomyopathy. - CoQ10 is generally safe in recommended dosages, but further studies are needed. - Allergy associated with CoQ10 supplements has not been reported, although rash and itching have been reported rarely. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures. Use caution with a history of blood clots, diabetes, high blood pressure, heart attack, or stroke, or with anticoagulants (blood thinners), antiplatelet drugs (such as aspirin, warfarin, clopidogrel (e.g., Plavix®), or blood pressure, blood sugar, cholesterol or thyroid drugs. Avoid if pregnant or breastfeeding. - Ginseng: A clinical study on the effect of Panax ginseng on CHF did not show a clear benefit of combining digoxin with ginseng. The relatively small study size and the use of a drug instead of a standardized extract limit the value of the evidence. Additional research is needed. - Ginseng may also lower blood pressure. Caution is used when taking ginseng supplements, as adverse effects and drug interactions are possible. Ginseng supplements should not be used if pregnant or breastfeeding unless otherwise directed by a doctor. - Goldenseal: Limited available study suggests that berberine (the active compound of goldenseal) in addition to a standard prescription drug regimen for CHF may improve quality of life and decrease ventricular premature complexes (VPCs) and mortality. Further research is needed to confirm these results. - Use cautiously in patients with gastrointestinal disorders, cardiovascular disease, bleeding disorders or in those taking anticoagulants, diabetes or in those taking antidiabetic agents. Use cautiously in infants with increased bilirubin levels or individuals with glucose-6-phosphate deficiency. Use cautiously in pregnancy. - Hawthorn: Herbal combinations containing hawthorn have been found effective in the treatment of functional cardiovascular disorders. However, due to a lack of information on the use of hawthorn alone, there is not enough evidence to recommend for or against this use of hawthorn. - Avoid if allergic to hawthorn or to members of the Crataegus species. Avoid with a history of low blood pressure, irregular heartbeat, asthma, low blood pressure when standing, or insomnia. Use cautiously in elderly patients. Avoid if pregnant or breastfeeding. - L-carnitine: L-carnitine, carnitine, or acetyl-L-carnitine, is an amino acid found in the body. Although preliminary results are promising, there is insufficient available clinical evidence for the use of L-carnitine in CHF. - Avoid with a known allergy or hypersensitivity to carnitine. Use cautiously with peripheral vascular disease, hypertension (high blood pressure), alcohol-induced liver cirrhosis, and diabetes. Use cautiously in low birthweight infants and individuals on hemodialysis. Use cautiously if taking anticoagulants (blood thinners), beta-blockers, or calcium channel blockers. Avoid if pregnant or breastfeeding. - Meditation: Meditation may improve quality of life in elderly patients, and may potentially reduce the risk for CHF. However, there is not enough evidence to make a conclusion. - Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professional(s) before starting a program of meditation, and should explore how meditation may or may not fit in with their current treatment plan. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses. - Oleander: The term oleander refers to two plants: Nerium oleander (common oleander) and Thevetia peruviana (yellow oleander). Both plants contain heart-active cardiac glycoside chemicals (similar to the prescription drug digoxin) and have been associated with serious side effects in humans, including death. The plants have been used to treat CHF in China and Russia for decades, but scientific evidence supporting this use is limited to small, poorly designed studies. Human research began in the 1930s, but was largely abandoned due to serious gastrointestinal and heart toxicity. - All parts of the oleander plant, including flowers, leaves, and nectar are considered toxic and may cause death. Avoid if allergic to oleander or other cardiac glycosides such as digoxin. Avoid with a history of irregular heartbeat (arrhythmia), seizures, liver or kidney disease, depression, or asthma. Avoid if pregnant or breastfeeding. - Passion flower: An extract containing passionflower and hawthorn has been studied for potential enhancement of exercise capacity in CHF patients. Individuals using this combination of herbs have experienced improvements in symptoms; however, any positive effects may have resulted from hawthorn, which is more commonly used for congestive heart failure. High quality human research of passion flower alone and compared to prescription drugs used for this condition is needed. - Avoid if allergic to passionflower or any of its constituents. Avoid consuming raw Passiflora fruit (Passiflora adenopoda), due to possible cyanide constituents. Passionflower extracts may cause drowsiness in sensitive individuals. Avoid driving or operating heavy machinery while taking passionflower. Use cautiously with low blood pressure. Avoid if pregnant or breastfeeding. - Physical therapy: Both supervised and home-based exercise training may enhance exercise capacity in patients with CHF. However, consensus has not been obtained regarding a standard rehabilitation program for these patients, and the literature often suggests individually-tailored programs. Due to the lack of standardization, duration of treatment, and various outcomes' measures, more study is needed before a conclusion can be made. - Not all physical therapy programs are suited for everyone, and patients should discuss their medical history with a qualified healthcare professional before beginning any treatments. Physical therapy may aggravate pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or cause limitation of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported in the literature although causality is unclear. Erectile dysfunction has also been reported. Physical therapy has been used in pregnancy and although reports of major adverse effects are lacking in the available literature, caution is advised nonetheless. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation. - Relaxation therapy: Early studies suggest that progressive muscle relaxation training may benefit patients with heart failure when used in combination with standard care. - Avoid with psychiatric disorders such as schizophrenia/psychosis. Jacobson relaxation (flexing specific muscles, holding that position, and then relaxing the muscles) should be used cautiously with illnesses such as heart disease, high blood pressure, or musculoskeletal injury. Relaxation therapy is not recommended as the sole treatment approach for potentially serious medical conditions, and should not delay the time to diagnosis or treatment with more proven techniques. - Selenium: Low selenium levels have been associated with the development of cardiomyopathy, and selenium supplementation is likely of benefit in such cases (for example in Keshan disease and Chagas' disease). However, most cases of cardiomyopathy are not due to low selenium levels and therefore selenium may not be helpful. It has been suggested that low selenium levels may be a risk factor for coronary heart disease, although this remains unclear. - Avoid if allergic or sensitive to products containing selenium. Avoid with a history of nonmelanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects. - Taurine: Taurine is a nonessential amino acid-like compound, found in high abundance in the tissues of many animals, especially sea animals, and in much lower concentrations in plants, fungi, and some bacteria. Preliminary study suggests that taurine may be beneficial as an adjunct to traditional medications for symptoms of CHF. Further study is warranted to confirm these findings. - Taurine appears to be safe in recommended dosages. As an amino acid, it is unlikely that there are allergies related to this constituent. However, allergies may occur from multi-ingredient products that contain taurine. Use cautiously in patients with high cholesterol, low blood pressure, coagulation disorders, potential for mania, or epilepsy. Avoid alcohol or exercise after consumption of energy drinks containing taurine, caffeine, glucuronolactone, B vitamins, and other ingredients. Use cautiously if pregnant or breastfeeding; taurine is a natural component of breast milk - Thiamin: Thiamin (also spelled "thiamine") is a water-soluble B-complex vitamin, previously known as vitamin B1 or aneurine. Thiamin was isolated and characterized in the 1920s, and thus was one of the first organic compounds to be recognized as a vitamin. Chronic severe thiamin deficiency may cause heart failure (wet beriberi), a condition that merits thiamin supplementation. Currently, it is not clear if thiamin supplementation is beneficial in patients with heart failure due to other causes. However, it is reasonable for patients with heart failure to take a daily multivitamin including thiamin, because some of these individuals may be thiamin deficient. Diuretics may lower thiamin levels. Since diuretics are commonly administered to patients with heart failure, patients taking diuretics are at an increased risk of thiamin deficiency. This area remains controversial, and further evidence is necessary before a conclusion can be reached. Excessive alcohol consumption may cause thiamin deficiency. - Avoid if allergic or hypersensitive to thiamin. Rare hypersensitivity/allergic reactions have occurred with thiamin supplementation. Skin irritation, burning, or itching may rarely occur at injection sites. Large doses may cause drowsiness or muscle relaxation. Use cautiously if pregnant or breastfeeding with doses higher than the U.S. Recommended Daily Allowance (RDA). - Thymus extract: The thymus is a lobular gland located under the breastbone near the thyroid gland. It reaches its maximum size during early childhood and plays a large role in immune function. Preliminary evidence suggests that thymus extract may increase left ventricular function, exercise tolerance, and survival in patients with cardiomyopathy. Additional research is needed to confirm these results. - It is important to use high quality thymus gland supplements due to contamination concerns. Avoid if allergic or hypersensitive to thymus extracts. Use bovine thymus extract supplements cautiously due to potential for exposure to the virus that causes mad cow disease. Avoid use with an organ transplant or other forms of allografts or xenografts. Avoid if receiving immunosuppressive therapy, with thymic tumors, myasthenia gravis (neuromuscular disorder), untreated hypothyroidism, or if taking hormonal therapy. Avoid if pregnant or breastfeeding; thymic extract increases human sperm motility and progression. - Traditional Chinese medicine (TCM): Many studies of traditional Chinese medicine (TCM) herbs have focused on treatment of CHF. Further research of better design is needed before recommendations can be made. - Chinese herbs can be potent and may interact with other herbs, foods or drugs. Consult a qualified healthcare professional before taking. There have been reports of manufactured or processed Chinese herbal products being tainted with toxins or heavy metals or not containing the listed ingredients. Herbal products should be purchased from reliable sources. Avoid ma huang, which is the active ingredient in ephedra. Avoid ginseng if pregnant or breastfeeding. - Fair negative scientific evidence: - Guided imagery: Therapeutic guided imagery may be used to help individuals relax and focus on images associated with personal issues they are confronting. Preliminary human research does not report benefits of guided imagery in congestive heart failure (CHF). - Guided imagery is usually intended to supplement medical care, not to replace it, and guided imagery should not be relied on as the sole therapy for a medical problem. Contact a qualified healthcare provider if mental or physical health is unstable or fragile. Never use guided imagery techniques while driving or doing any other activity that requires strict attention. Use cautiously with physical symptoms that may be brought about by stress, anxiety, or emotional upset because imagery may trigger these symptoms. If feeling unusually anxious while practicing guided imagery, or with a history of trauma or abuse, speak with a qualified healthcare provider before practicing guided imagery. - General: Coronary artery disease (CAD) and hypertension (high blood tension) may cause or worsen existing cardiomyopathy. Therefore, preventative measures for cardiomyopathy aim at reducing the risk of CAD. - Smoking cessation: Smoking damages blood vessels, reduces the amount of oxygen in the blood, and makes the heart beat faster. If an individual smokes, a doctor may help recommend a program or treatment option to help them quit. Individuals are not considered for a heart transplant if smoking is continued. - Weight control: It is recommended that individuals weigh themselves each morning after urination, but before breakfast. Notify a doctor if there is a weight gain of three or more pounds in a day. Weight gain may indicate fluid build-up. - Being overweight contributes to other risk factors for stroke, such as high blood pressure, cardiovascular disease, and diabetes. Weight loss of as little as ten pounds may lower blood pressure and improve cholesterol levels. - Exercise may lower blood pressure, increase the level of high density lipoprotein (HDL cholesterol or good cholesterol), and improve the overall health of blood vessels and heart. It also helps control weight, control diabetes, and reduce stress. Cardiac rehabilitation programs exist for individuals recovering from heart surgery. Cardiac rehabilitation is a medically supervised program to help heart patients recover quickly and improve their overall physical, mental, and social functioning. The goal is to stabilize, slow, or even reverse the progression of cardiovascular disease, thereby reducing the risk of heart disease, another cardiac event, or death. Cardiac rehabilitation programs include: counseling so the individual can understand and manage the disease process; an exercise program; counseling on nutrition; helping the patient modify risk factors such as high blood pressure, smoking, high blood cholesterol, physical inactivity, obesity, and diabetes; providing vocational guidance to enable the patient to return to work; information on physical limitations; lending emotional support; and counseling on appropriate use of prescribed medications. A doctor may help initiate an exercise program and cardiac rehabilitation tailored to the individual with congestive heart failure (CHF). - Salt restriction: Too much sodium (from salt) contributes to water retention, which makes the heart work harder. Excess sodium may causes shortness of breath and swollen legs, ankles, and feet. For individuals with heart failure the recommended sodium intake is no more than 2,000 milligrams daily. Some substitutes or "lite" salts contain a mixture of salt and other compounds. To get that familiar salty taste, individuals may use too much of the substitute and actually not reduce sodium intake. In addition, many salt substitutes contain potassium chloride. Too much potassium may be harmful. A dietitian may help outline a healthy, low-salt diet. - Stress management: Stress may cause an increase in blood pressure along with increasing the blood's tendency to clot. Managing stress may be vital to keeping a heart healthy. - Diet modification: Eating healthy foods is important. A heart-healthy diet includes five or more daily servings of fruits and vegetables, foods rich in soluble fiber (such as oatmeal and beans), foods rich in calcium (dairy products, spinach), soy products (such as tempeh, miso, tofu, and soy milk), and foods rich in omega-3 fatty acids, including cold-water fish, such as salmon, mackerel, and tuna. Pregnant women and women who plan to become pregnant in the next several years should limit their weekly intake of cold-water fish because of the potential for mercury contamination. Limiting red meats and high fat foods (such as doughnuts, cookies, and chips) is recommended by healthcare professionals. - Alcohol: Excessive use of alcohol may weaken the heart muscle or increase the risk of abnormal heart rhythms, increasing the risk of cardiomyopathy and resultant heart failure. Alcohol may also interact with some medications used to treat heart conditions. However, moderate alcohol consumption (such as one glass of red wine daily) may be beneficial for heart health. - Swelling: Leg, ankle, and foot edema can be improved by elevating the legs above heart level for 30 minutes 3-4 times daily. Leg elevation alone may be sufficient therapy for patients with mild venous insufficiency, but is usually not adequate for more severe cases. In addition, it may not be practical for those who work to elevate their legs several times daily. - Leg edema (swelling) can also be prevented and treated with the use of compression stockings. Many types are available, including knee-high, thigh-high, and pantyhose. Knee-high stockings are sufficient for most individuals; thigh-high stockings are less desirable because they tend to provide too much pressure behind the knees, reducing blood flow in the veins, and causing discomfort. The stockings should be put on as early as possible in the morning when edema is minimal. Healthcare professionals can help with choosing the right compression stocking for each individual. - Contraception: Because women who have previously had peripartum cardiomyopathy are at increased risk of developing cardiomyopathy with future pregnancies, they may consider contraception to prevent future pregnancies. - This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com). - Allard ML, Jeejeebhoy KN, Sole MJ. The management of conditioned nutritional requirements in heart failure. Heart Fail Rev. 2006 Mar;11(1):75-82. - American Heart Association (AHA). . - Centers for Disease Control and Prevention (CDC). . - Dauchet L, Amouyel P, Hercberg S, et al. Fruit and vegetable consumption and risk of coronary heart disease: a meta-analysis of cohort studies. J Nutr. 2006 Oct;136(10):2588-93. - Hunt SA; American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol. 2005 Sep 20;46(6):e1-82. - Hypertrophic Cardiomyopathy Association. . - Kaski JP, Elliott P; ESC Working Group. The classification concept of the ESC Working Group on myocardial and pericardial diseases for dilated cardiomyopathy. Herz. 2007 Sep;32(6):446-51. - Maron BJ, Thompson PD, Ackerman MJ, et al. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation. 2007 Mar 27;115(12):1643-455. - Maron BJ, Towbin JA, Thiene G, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation. 2006 Apr 11;113(14):1807-16. - National Heart, Lung, and Blood Institute (NHLBI). . - National Institutes of Health (NIH). . - Natural Standard: The Authority on Integrative Medicine. . - Riegel B, Moser DK, Powell M, et al. Nonpharmacologic care by heart failure experts. J Card Fail. 2006 Mar;12(2):149-153. - Sen-Chowdhry S, Morgan RD, Chambers JC, et al. Arrhythmogenic cardiomyopathy: etiology, diagnosis, and treatment. Annu Rev Med. 2010;61:233-53. - Wexler RK, Elton T, Pleister A, et al. Cardiomyopathy: an overview. Am Fam Physician. 2009 May 1;79(9):778-84. - General: Cardiomyopathy refers to several diverse diseases that affect the myocardium (heart muscle). Different forms of cardiomyopathy have distinct causes. Primary cardiomyopathies may be inherited, acquired, or both. Secondary cardiomyopathies are caused by other conditions, including diabetes, thyroid disorders, chronic alcohol consumption, infection, or drugs/toxins (e.g., heavy metals, anthracyclines, cocaine). - Arrhythmogenic right ventricular cardiomyopathy (ARVC): Arrhythmogenic right ventricular cardiomyopathy (ARVC, formerly known as arrhythmogenic right ventricular dysplasia or ARVD) is a genetic disease caused by mutations in genes that affect heart muscle cells. The most common genetic causes of ARVC are mutations in the plakophilin 2 (PKP2) gene, which produces a protein that helps myocardial cells attach to each other. Mutations in PKP2 that cause ARVD result in defective forms of the plakophilin 2 protein. Although mutations in PKP2that cause ARVC are usually autosomal dominant, which means that they would affect both sexes equally, ARVC occurs in men three times more often than in women. It is unclear why more men are affected; however, it appears that physical activity may increase the risk of arrhythmia (abnormal heart beat) in ARVD. - Dilated cardiomyopathy: There are multiple factors (primary or secondary) that may cause different forms of dilated cardiomyopathy. The most common form, ischemic cardiomyopathy, is most often caused by coronary artery disease (CAD) and/or high blood pressure; however, viral infections, other heart diseases, or genetics may also lead to ischemic cardiomyopathy. Peripartum cardiomyopathy is diagnosed in pre- or postnatal mothers when other known causes of dilated cardiomyopathy have been excluded. It is unclear what exactly causes peripartum cardiomyopathy; however, risk factors include obesity, pregnancy-induced hypertension (preeclampsia), multiple pregnancy (such as twins or triplets), or being more than 30 years of age. Stress (physical or emotional) or excessive alcohol consumption may also cause dilated cardiomyopathy - Hypertrophic cardiomyopathy (HCM): Hypertrophic cardiomyopathy (HCM) is a genetic disease caused by mutations in genes that produce sarcomere proteins. Sarcomeres are units of myofibrils, which are threadlike strands that make up the muscle that contracts the heart. Because HCM is usually inherited, having a parent with the condition increases the risk of inheriting the gene that causes HCM. While HCM is often asymptomatic, physical activity greatly increases the risk of complications and sudden death, due to HCM. - Restrictive cardiomyopathy: Restrictive cardiomyopathy is usually secondary to another acquired or inherited heart disease (such as amyloidosis, endomyocardial fibrosis, or sarcoidosis). It may also occur after a heart transplant, and having any disease or injury that affects the heart muscle may increase the risk of restrictive cardiomyopathy. Heritable forms of restrictive cardiomyopathy are most often caused by mutations in genes that produce troponin, a muscle protein that aids in muscle contraction. - Arrhythmogenic right ventricular cardiomyopathy (ARVC): Arrhythmogenic right ventricular cardiomyopathy (ARVC, formerly known as arrhythmogenic right ventricular dysplasia or ARVD) is a genetic disease that can be passed through families. Having a parent with ARVC increases the risk of developing the condition. ARVC occurs in men three times more often than in women; however, it is unclear why more men are affected. Physical activity may increase the risk of arrhythmia (abnormal heart beat) in ARVD. - Dilated cardiomyopathy: Because there are multiple factors (primary or secondary) that can cause the different forms of dilated cardiomyopathy, there are also many different risk factors. For the most common form of dilated cardiomyopathy, ischemic cardiomyopathy, major risk factors are coronary artery disease (CAD) and high blood pressure. However, viral infections, other heart diseases, or genetics may also increase the risk of ischemic cardiomyopathy. For peripartum cardiomyopathy that occurs in women during the last month of pregnancy or first five months following birth, risk factors include obesity, pregnancy-induced hypertension (preeclampsia), multiple pregnancy (such as twins or triplets), or being more than 30 years of age. Women who have previously had peripartum cardiomyopathy are also at increased risk of developing cardiomyopathy with future pregnancies. Physical or emotional stress may worsen (or even cause) cardiomyopathy. Excessive alcohol consumption may also increase the risk of dilated cardiomyopathy. - Hypertrophic cardiomyopathy (HCM): Like ARVC, hypertrophic cardiomyopathy (HCM) is also a genetic disease that is inherited. Having a parent with the condition increases the risk of developing HCM. While HCM is often asymptomatic (without symptoms), physical activity greatly increases the risk of complications (e.g., atrial fibrillation) and death, due to HCM. - Restrictive cardiomyopathy: Restrictive cardiomyopathy is usually secondary to another acquired or inherited heart disease (such as amyloidosis, endomyocardial fibrosis, or sarcoidosis). It may also occur after a heart transplant. Having any disease or injury that affects the heart muscle may increase the risk of restrictive cardiomyopathy. Having a parent with the condition increases the risk of heritable forms of restrictive cardiomyopathy. Types of the disease - There are four main types of cardiomyopathy as defined by the American Heart Association (AHA): arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy, hypertrophic cardiomyopathy (HCM), and restrictive cardiomyopathy. Dilated cardiomyopathy may result from multiple causes and is the most common form of cardiomyopathy that affects the overall population of North America. HCM is genetic in origin, and is the most common cause of sudden death in athletes. Restrictive cardiomyopathy and ARVC are considered to be rarer forms of the disease. - The different types of cardiomyopathy are further classified by the AHA as primary or secondary. Primary cardiomyopathies cannot be attributed to other conditions (such as heart disease). Instead, they may be caused by genetic (inherited) factors, acquired factors, or a combination of genetic and acquired traits. Acquired causes of cardiomyopathy include inflammatory cardiomyopathy (myocarditis), post- or peripartum cardiomyopathy, and stress cardiomyopathy (broken heart syndrome). Secondary cardiomyopathy occurs as a result of another condition, such as an infection or a metabolic disease (e.g., diabetes or coronary heart disease). - Arrhythmogenic right ventricular cardiomyopathy (ARVC): Arrhythmogenic right ventricular cardiomyopathy (ARVC, formerly known as arrhythmogenic right ventricular dysplasia or ARVD) is a genetic disease that causes the myocardium to become fatty and fibrous. Though it mainly affects the right ventricle of the heart, it may also affect the left ventricle. In contrast to other forms of cardiomyopathy, ARVC seldom results in heart failure. However, it does cause abnormal heart function such as arrhythmia (abnormal heartbeat), which may be fatal. - Dilated cardiomyopathy: In dilated cardiomyopathy, the myocardium becomes weak, enlarged, and unable to pump blood efficiently. The prevalence of dilated cardiomyopathy in the United States is 36 per 100,000. It is considered the most common form of cardiomyopathy. After coronary artery disease (CAD) and hypertension (high blood pressure), dilated cardiomyopathy is the third most common cause of heart failure in the United States. - There are several types of dilated cardiomyopathy, which are caused by multiple factors (primary or secondary). The three types of dilated cardiomyopathy include ischemic cardiomyopathy, peripartum cardiomyopathy, and stress cardiomyopathy. - Ischemic cardiomyopathy is the most common form of dilated cardiomyopathy. It is most often caused by CAD or high blood pressure; however, viral infections, other heart diseases, or genetics may also contribute to ischemic cardiomyopathy. - Peripartum cardiomyopathy is usually diagnosed in women in their last month of pregnancy, or in the first five months following birth (also called postpartum cardiomyopathy). Although it is rare (affecting one in 1,000-4,000 live births), peripartum cardiomyopathy is more prevalent in women who are over age 30, obese, have pregnancy-induced hypertension (preeclampsia), or multiple births. - Excessive alcohol use may also cause dilated cardiomyopathy. - Hypertrophic cardiomyopathy (HCM): In hypertrophic cardiomyopathy (HCM), the myocardium is thickened. As a result, it becomes difficult for the heart to pump blood. Nearly one-half of deaths due to HCM occur during or after physical activity. Sudden death occurs due to lethal heart rhythm disturbances (ventricular fibrillation and ventricular tachycardia). It is the most common cause of sudden cardiac death in athletes as a result of structural heart changes in response to intense training. Because HCM is typically an inherited disorder, it is also called familial HCM. It is estimated that one of 500 people has the gene for HCM. However, it may also be acquired resulting from high blood pressure or aortic stenosis (narrowing or obstruction of the aortic valve causing restricted blood flow). Symptoms of HCM include chest pain, shortness of breath, dizziness, palpitations, and fatigue. - Restrictive cardiomyopathy: In restrictive cardiomyopathy, the heart is unable to function properly, due to stiffness of the myocardium. The heart is usually normal size (or slightly larger), but the myocardium of one or both ventricles (cavities or chambers) cannot relax after each heartbeat because of stiffness in the heart. Instead, the ventricles are restricted and do not fill with enough blood. Restrictive cardiomyopathy may have a genetic cause, or it may result from another myocardial disease. - Other: Stress cardiomyopathy (also known as broken heart syndrome or Takotsubo cardiomyopathy) is triggered by sudden intense physical or emotional stress (e.g., death of a loved one, fear, extreme anger). The clinical presentation is similar to that of a heart attack. The most common symptoms are chest pain, shortness of breath, and low blood pressure. Copyright © 2011 Natural Standard (www.naturalstandard.com) The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.	2	10	0	0	0	1	0.957885	1	15,632
What Are the Different Types of Medical Coding Classification Systems? Two common medical coding classification systems are in use — the International Classification of Diseases (ICD) and the Current Procedural Terminology (CPT). ICD is the standard international system of classifying mortality and morbidity statistics, and it’s used by more than 100 countries. The system is used by health care facilities to define diseases and allocate resources to provide care. According to the World Health Organization (WHO), 70% of the world’s health care expenditures are allocated using ICD. The current version, ICD-9, features more than 16,000 codes for infections and parasitic diseases, neoplasms, and congenital malformations, as well as diseases of the digestive system, respiratory system, and nervous system. ICD codes are alphanumeric designations given to every diagnosis, description of symptoms and cause of death attributed to human beings. These classifications are developed, monitored, and copyrighted by the World Health Organization (WHO). In the U.S., the NCHS (National Center for Health Statistics), part of CMS (Centers for Medicare & Medicaid Services) oversees all changes and modifications to the ICD codes, in cooperation with WHO. The ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) coding system, connects health issues that arise in patients, by using three- to five-digit alphanumeric codes to indicate signs, symptoms, diseases, conditions, and injuries to payers injuries, diseases, and conditions. These codes are used in conjunction with CPT (procedural) codes to record services rendered by a provider to a patient and is documented in the medical record and then reported to a payer for reimbursement. Note: Medical necessity is the overarching criteria for a service and the diagnosis code is used to indicate medical necessity in conjunction with a CPT code. On Oct. 1, 2014, ICD-10 will be implemented and will be the standard coding system for the U.S. ICD-10 is currently used by the rest of the world to report health care conditions. The most current list of codes in use is ICD-10 which is beginning to be implemented in the U.S. It will give billing and coding professionals and providers the ability to report conditions, diseases, and injuries with more accurate specificity, which will provide clearer information overall about a person’s health status and allow for better outcomes and care. CPT (Current Procedural Terminology) codes are published by the American Medical Association, and there are approximately 7,800 CPT codes ranging from 00100 through 99499, currently at use. The U.S. and other countries use the fourth edition and they were designed to provide a uniform data set that could be used to describe medical, surgical, and diagnostic services rendered to patients. CPT codes are five-digit alphanumeric codes and consist of five numbers and occasionally may have four numbers and letter, depending on the type of service. CPT codes are used to identify services provided to patients such as, medical, surgical, diagnostic, and radiological services. These codes are submitted with ICD-9 codes on claim forms to payers and that is what is used to determine reimbursement to a provider/facility. The AMA has implemented the CPT Editorial Panel, which meets three times a year, which reviews and discusses issues that are relevant to any new or upcoming technology and identified problems encountered with any procedure and how it relates to a specific code. Medical billing and coding professionals and providers use these two classifications systems on a daily basis, and they are the “bibles” and building blocks for this industry. Every year, it is mission critical for billers and coders to obtain the new versions of both these code sets to stay abreast of any changes to codes in either of these classification systems, otherwise they will risk denied claims and potential compliance issues.	3	2	2	0	0	0	0.789044	2	817
Diagnosis of Asperger syndrome Several factors complicate the diagnosis of Asperger syndrome (AS), an autism spectrum disorder (ASD). Like other ASD forms, Asperger syndrome is characterized by impairment in social interaction accompanied by restricted and repetitive interests and behavior; it differs from the other ASDs by having no general delay in language or cognitive development. Problems in diagnosis include disagreement among diagnostic criteria, controversy over the distinction between AS and other ASD forms or even whether AS exists as a separate syndrome, and over- and under-diagnosis for non-technical reasons. As with other ASD forms, early diagnosis is important, and differential diagnosis must consider several other conditions. Asperger syndrome is defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) as a pervasive developmental disorder that is distinguished by a pattern of symptoms rather than a single symptom. It is characterized by impairment in social interaction, by stereotyped and restricted patterns of behavior, activities and interests, and by no clinically significant delay in cognitive development or general delay in language. Impairments must be significant, and must affect important areas of function, and the diagnosis is excluded if criteria are also met for autism. Intense preoccupation with a narrow subject, one-sided verbosity, restricted prosody, and physical clumsiness are typical of the condition, but are not required for diagnosis. The World Health Organization ICD-10 criteria are almost identical to DSM-IV: ICD-10 adds the statement that motor clumsiness is usual (although not necessarily a diagnostic feature); ICD-10 adds the statement that isolated special skills, often related to abnormal preoccupations, are common but are not required for diagnosis; and the DSM-IV requirement for clinically significant impairment in social, occupational, or other important areas of functioning is not included in ICD-10. Diagnosis of Asperger syndrome can be tricky as there is a lack of a standardized diagnostic screening for the disorder. According to the National Institute of Neurological Disorders and Stroke, physicians look for the presence of a primary group of behaviors to make a diagnosis such as abnormal eye contact, aloofness, failure to respond when called by name, failure to use gestures to point or show, lack of interactive play with others, and a lack of interest in peers. The diagnoses of AS or high-functioning autism (HFA) are sometimes used interchangeably; the same child can receive different diagnoses depending on the screening tool and the individual administering the test. Diagnoses may be influenced by non-technical issues, such as availability of government benefits for one condition but not the other. Advocacy and parent support organizations have proliferated around the concept of AS, and there are indications that this has resulted in more frequent diagnoses of AS, which may be given as a "residual diagnosis" to children of normal intelligence who do not meet diagnostic criteria for autism but have some social difficulties. Underdiagnosis and overdiagnosis are problems in marginal cases; the increasing popularity of drug treatment options and the expansion of benefits has given providers incentives to diagnose ASD, resulting in some overdiagnosis of children with uncertain symptoms. Conversely, the cost of screening and diagnosis and the challenge of obtaining payment can inhibit or delay diagnosis. Developmental screening during a routine check-up by a general practitioner or pediatrician may identify signs that warrant further investigation. This will require a comprehensive team evaluation to either confirm or exclude a diagnosis of AS. This team usually includes a psychologist, neurologist, psychiatrist, speech and language pathologist, occupational therapist and other professionals with expertise in diagnosing children with AS. Observation occurs across multiple settings; the social disability in AS may be more evident during periods when social expectations are unclear and children are free of adult direction. A comprehensive evaluation includes neurological and genetic assessment, with in-depth cognitive and language testing to establish IQ and evaluate psychomotor function, verbal and nonverbal strengths and weaknesses, style of learning, and skills for independent living. An assessment of communication strengths and weaknesses includes the evaluation of nonverbal forms of communication (gaze and gestures); the use of non-literal language (metaphor, irony, absurdities and humor); patterns of speech inflection, stress and volume; pragmatics (turn-taking and sensitivity to verbal cues); and the content, clarity and coherence of conversation. Testing may include an audiological referral to exclude hearing impairment. The determination of whether there is a family history of autism spectrum conditions is important. A medical practitioner will diagnose on the basis of the test results and the person's developmental history and current symptoms. Because multiple domains of functioning are involved, a multidisciplinary team approach is critical; an accurate assessment of the individual's strengths and weaknesses is more useful than a diagnostic label. Delayed or mistaken diagnosis is a serious problem that can be traumatic for individuals and families; diagnosis based solely on a neurological, speech and language, or educational attainment may yield only a partial diagnosis. Advances in genetic technology allow clinical geneticists to link an estimated 40% of ASD cases to genetic causes; in one study the diagnostic yield for AS, PDD-NOS and atypical autism was similar to that for classic autism. Genetic diagnosis is relatively expensive, and genetic screening is generally impractical. As genetic tests are developed several ethical, legal, and social issues will emerge. Commercial availability of tests may precede adequate understanding of how to use test results, given the complexity of the genetics. Parents of children with AS can typically trace differences in their children's development to as early as 30 months of age, although diagnosis is not made on average until the age of 11. By definition, children with AS develop language and self-help skills on schedule, so early signs may not be apparent and the condition may not be diagnosed until later childhood or even old age. Impairment in social interaction is sometimes not in evidence until a child attains an age at which these behaviors become important; social disabilities are often first noticed when children encounter peers in daycare or preschool. Diagnosis is most commonly made between the ages of four and eleven, and one study suggests that diagnosis cannot be rendered reliably before age four. Asperger syndrome can be misdiagnosed as a number of other conditions, leading to medications that are unnecessary or even worsen behavior; the condition may be at the root of treatment-resistant mental illness in adults. Diagnostic confusion burdens individuals and families and may cause them to seek unhelpful therapies. Conditions that must be considered in a differential diagnosis include other pervasive developmental disorders (autism, PDD-NOS, childhood disintegrative disorder, Rett disorder), schizophrenia spectrum disorders (schizophrenia, schizotypal disorder, schizoid personality disorder), attention-deficit hyperactivity disorder, obsessive compulsive disorder, depression, semantic pragmatic disorder, multiple complex developmental disorder and nonverbal learning disorder (NLD). Differentiating between AS and other ASDs relies on the judgment of experienced clinicians. There is much overlap between AS and NLD: both have symptoms of precocious reading, verbosity, and clumsiness, but they differ in that children with AS have restricted interests, repetitive behaviors, and less-typical social interactions. Tourette syndrome (TS) should also be considered in differential diagnosis: "It is in nonretarded, rigid individuals on the autistic spectrum, especially those with so-called Asperger syndrome, that differences with less severely affected individuals with TS and obsessive compulsive disorder may become blurred, or that both disorders may coexist." Other problems to be considered in the differential diagnosis include selective mutism, stereotypic movement disorder and bipolar disorder as well as traumatic brain injury or birth trauma, conduct disorder, Cornelia De Lange syndrome, fetal alcohol syndrome, fragile X syndrome, dyslexia, Fahr syndrome, hyperlexia, leukodystrophy, multiple sclerosis and Triple X syndrome. Multiple sets of diagnostic criteria The diagnosis of AS is complicated by the use of several different screening instruments. In addition to the DSM-IV and the ICD-10 criteria, other sets of diagnostic criteria for AS are the Szatmari et al. criteria and the Gillberg and Gillberg criteria. \|Partial Diagnostic Criteria for Asperger Syndrome Adapted from Mattila et al. Blank = not defined by the criteria Substantial differences between criteria listed: all sub-sections of criteria not included \|Cognitive development delay\|\|No\|\|No\| \|Self-help skill delay\|\|No\|\|No\| \|Social interaction impairment\|\|Yes\|\|Yes\|\|Yes\|\|Yes\| \|– Impaired nonverbal communication\|\|Maybe\|\|Maybe\|\|Yes\|\|Yes\| \|– Inadequate friendships\|\|Maybe\|\|Maybe\|\|Maybe\|\|Yes\| \|Repetitive, stereotyped behavior\|\|Yes\|\|Yes\|\|Yes\| \|– All-absorbing interest\|\|Maybe\|\|Maybe\|\|Yes\| \|– Routines or rituals\|\|Maybe\|\|Maybe\|\|Yes\| \|Isolated special skills\|\|Common\| \|Clinically significant impairmenta\|\|Yes\| \|Exclusion of other disorder\|\|Yesb\|\|Yesc\|\|No\|\|Yesd\| \|a Impairment in social, occupational, or other important areas of functioning b Does not meet criteria for another pervasive developmental disorder or schizophrenia c Not attributed to pervasive developmental disorder, schizotypal disorder, simple schizophrenia, reactive and disinhibited attachment disorder, obsessional personality disorder, obsessive compulsive disorder d Does not meet criteria for autistic disorder Compared with the DSM-IV and ICD-10 criteria, the requirements of normal early language and cognitive development are not mentioned by Szatmari et al., whereas language delay is allowed in the Gillberg and Gillberg criteria. Szatmari et al. emphasize solitariness, and both Gillberg and Szatmari include "odd speech" and "language" in their criteria. Although Szatmari does not mention stereotyped behaviors, one of four described stereotyped functions is required by DSM-IV and ICD-10, and two are required by Gillberg and Gillberg. Abnormal responses to sensory stimuli are not mentioned in any diagnostic scheme, although they have been associated with AS. Because DSM-IV and ICD-10 exclude speech and language difficulties, these definitions exclude some of the original cases described by Hans Asperger. According to one researcher, the majority of individuals with AS do have speech and language abnormalities, and the recent DSM–IV says that "the occurrence of 'no clinically significant delays in language does not imply that individuals with Asperger Disorder have no problems with communication' (American Psychiatric Association, 2000, p. 80)". The Gillberg and Gillberg criteria are considered closest to Asperger's original description of the syndrome; the aggression and abnormal prosody that other authors say defined Asperger's patients are not mentioned in any criteria. The DSM-IV and ICD-10 diagnostic criteria have been criticized for being too broad and inadequate for assessing adults, overly narrow (particularly in relation to Hans Asperger's original description of individuals with AS), and vague; results of a large study in 2007 comparing the four sets of criteria point to a "huge need to reconsider the diagnostic criteria of AS". The study found complete overlap across all sets of diagnostic criteria in the impairment of social interaction with the exception of four cases not diagnosed by the Szatmari et al. criteria because of its emphasis on social solitariness. Lack of overlap was strongest in the language delay and odd speech requirements of the Gillberg and the Szatmari requirements relative to DSM-IV and ICD-10, and in the differing requirements regarding general delays. A small 2008 study of children referred with a tentative diagnosis of AS found poor agreement among the four sets of criteria, with one overlap being only 39%. In 2007 Szatmari et al. suggested a new classification system of ASD based on familial traits found by genetic epidemiology. Differences from high-functioning autism The distinction between Asperger's and other ASD forms is to some extent an artifact of how autism was discovered. Although individuals with Asperger's tend to perform better cognitively than those with autism, the extent of the overlap between Asperger's and high-functioning autism is unclear. Overall, relatively few differences are reported between Asperger's and autism on parameters related to causation. A standard assumption is that Asperger's and autism have a common cause, and are variable expressions of the same underlying disorder. A 2008 review of classification studies found that results largely did not support differences between the diagnoses, and that the most salient group characteristics came from IQ characterizations. The current ASD classification may not reflect the true nature of the conditions. A panel session at a 2008 diagnosis-related autism research planning conference noted problems with the classification of AS as a distinct subgroup of ASD, and two of three breakout groups recommended eliminating AS as a separate diagnosis. A neuropsychological profile has been proposed for AS; if verified, it could differentiate between AS and HFA and aid in differential diagnosis. Relative to HFA, people with AS have deficits in nonverbal skills such as visual-spatial problem solving and visual-motor coordination, along with stronger verbal abilities. Several studies have found AS with a neuropsychologic profile of assets and deficits consistent with a nonverbal learning disability, but several other studies have failed to replicate this. The literature review did not reveal consistent findings of "nonverbal weaknesses or increased spatial or motor problems relative to individuals with HFA", leading some researchers to argue that increased cognitive ability is evidenced in AS relative to HFA regardless of differences in verbal and nonverbal ability. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) which was published in May 2013 canceled Asperger's disorder as a separate diagnosis and homogenized it under autism spectrum disorder, with severity measures within the broader diagnosis. The DSM 5 noted that "Individuals with a well-established DSM-IV diagnosis of" "Asperger’s disorder" "should be given the diagnosis of autism spectrum disorder." The DSM 5 diagnostic criteria for Autism Spectrum Disorder states "A. Persistent deficits in social communication and social interaction across multiple contexts, as manifested by the following, currently or by history (examples are illustrative, not exhaustive; see text): Deficits in social-emotional reciprocity, ranging, for example, from abnormal social approach and failure of normal back-and-forth conversation; to reduced sharing of interests, emotions, or affect; to failure to initiate or respond to social interactions. Deficits in nonverbal communicative behaviors used for social interaction, ranging, for example, from poorly integrated verbal and nonverbal communication; to abnormalities in eye contact and body language or deficits in understanding and use of gestures; to a total lack of facial expressions and nonverbal communication. Deficits in developing, maintaining, and understanding relationships, ranging, for example, from difficulties adjusting behavior to suit various social contexts; to difficulties in sharing imaginative play or making friends; to absence of interest in peers." "B. Restricted, repetitive patterns of behavior, interests, or activities, as manifested by at least two of the following, currently or by history (examples are illustrative, not exhaustive; see text): Stereotyped or repetitive motor movements, use of objects, or speech (e.g., simple motor stereotypies, lining up toys or flipping objects, echolalia, idiosyncratic phrases). Insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or nonverbal behavior (e.g., extreme distress at small changes, difficulties with transitions, rigid thinking patterns, greeting rituals, need to take same route or eat same food every day). Highly restricted, fixated interests that are abnormal in intensity or focus (e.g., strong attachment to or preoccupation with unusual objects, excessively circumscribed or perseverative interests). Hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment (e.g., apparent indifference to pain/temperature, adverse response to specific sounds or textures, excessive smelling or touching of objects, visual fascination with lights or movement). Symptoms must be present in the early developmental period (but may not become fully manifest until social demands exceed limited capacities, or may be masked by learned strategies in later life). Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning. These disturbances are not better explained by intellectual disability (intellectual developmental disorder) or global developmental delay. Intellectual disability and autism spectrum disorder frequently co-occur; to make comorbid diagnoses of autism spectrum disorder and intellectual disability, social communication should be below that expected for general developmental level." The diagnosis is broken down into 3 levels of severity. The removal of Asperger's Disorder from the DSM has been controversial as it is commonly used by health insurers, researchers, state agencies, schools, and individuals with the disorder. Experts are concerned that eliminating the Asperger’s label will prevent mildly affected people from being evaluated for Autism. A meta-analysis of 14 studies published The Columbia University school of nursing in early 2014 showed that while there was a pooled 30% decrease in Autism Spectrum Disorder diagnoses following the publication of the DSM 5 the pooled decrease in Asperger's Disorder diagnosis was not statistically significant. - American Psychiatric Association (2000). "Diagnostic criteria for 299.80 Asperger's Disorder (AD)". Diagnostic and Statistical Manual of Mental Disorders (4th, text revision (DSM-IV-TR) ed.). ISBN 0-89042-025-4. Retrieved 2007-06-28. - Klin A (2006). "Autism and Asperger syndrome: an overview". Rev Bras Psiquiatr 28 (suppl 1): S3–S11. doi:10.1590/S1516-44462006000500002. PMID 16791390. - Fitzgerald M, Corvin A (2001). "Diagnosis and differential diagnosis of Asperger syndrome". Adv Psychiatric Treat 7 (4): 310–8. doi:10.1192/apt.7.4.310. - Mattila ML, Kielinen M, Jussila K et al. (2007). "An epidemiological and diagnostic study of Asperger syndrome according to four sets of diagnostic criteria". J Am Acad Child Adolesc Psychiatry 46 (5): 636–46. doi:10.1097/chi.0b013e318033ff42. PMID 17450055. - Baskin JH, Sperber M, Price BH (2006). "Asperger syndrome revisited". Rev Neurol Dis 3 (1): 1–7. PMID 16596080. - "Asperger Syndrome Fact Sheet". http://www.ninds.nih.gov. - Attwood, T (2003). Is There a Difference Between Asperger's Syndrome and High Functioning Autism? (PDF). Sacramento Asperger Syndrome Information & Support. Retrieved 2007-08-15. - Shattuck PT, Grosse SD (2007). "Issues related to the diagnosis and treatment of autism spectrum disorders". Ment Retard Dev Disabil Res Rev 13 (2): 129–35. doi:10.1002/mrdd.20143. PMID 17563895. - McPartland J, Klin A (2006). "Asperger's syndrome". Adolesc Med Clin 17 (3): 771–88. doi:10.1016/j.admecli.2006.06.010 (inactive 2008-06-22). PMID 17030291. - Foster B, King BH (2003). "Asperger syndrome: to be or not to be?". Curr. Opin. Pediatr. 15 (5): 491–94. doi:10.1097/00008480-200310000-00008. PMID 14508298. - Schaefer GB, Mendelsohn NJ (2008). "Genetics evaluation for the etiologic diagnosis of autism spectrum disorders". Genet Med 10 (1): 4–12. doi:10.1097/GIM.0b013e31815efdd7. PMID 18197051. Lay summary – Medical News Today (2008-02-07). - McMahon WM, Baty BJ, Botkin J (2006). "Genetic counseling and ethical issues for autism". Am J Med Genet C Semin Med Genet 142C (1): 52–7. doi:10.1002/ajmg.c.30082. PMID 16419100. - Stein MT, Klin A, Miller K, Goulden K, Coolman R, Coolman DM (2004). "When Asperger's syndrome and a nonverbal learning disability look alike". J Dev Behav Pediatr 25 (3): 190–5. doi:10.1097/00004703-200406000-00008. PMID 15194904. - Rapin I (2001). "Autism spectrum disorders: relevance to Tourette syndrome". Advances in neurology 85: 89–101. PMID 11530449. - Brasic, JR. Pervasive Developmental Disorder: Asperger Syndrome. eMedicine.com (April 10, 2006). Retrieved 15 July 2007. - Ehlers S, Gillberg C (1993). "The epidemiology of Asperger's syndrome. A total population study". J Child Psychol Psychiat 34 (8): 1327–50. doi:10.1111/j.1469-7610.1993.tb02094.x. PMID 8294522. "Truncated version". Archived from the original on 2008-07-19. Retrieved 2008-06-15. - Szatmari P, Bremner R, Nagy J (1989). "Asperger's syndrome: a review of clinical features". Canadian Journal of Psychiatry 34 (6): 554–60. PMID 2766209. - Gillberg IC, Gillberg C (Jul 1989). "Asperger syndrome-some epidemiological considerations: A research note". J Child Psychol Psychiatry 30 (4): 631–38. doi:10.1111/j.1469-7610.1989.tb00275.x. PMID 2670981. - Hippler K, Klicpera C (2003). "A retrospective analysis of the clinical case records of 'autistic psychopaths' diagnosed by Hans Asperger and his team at the University Children's Hospital, Vienna". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 358 (1430): 291–301. doi:10.1098/rstb.2002.1197. PMC 1693115. PMID 12639327. - Baron-Cohen S, Wheelwright S, Robinson J, Woodbury-Smith M (2005). "The Adult Asperger Assessment (AAA): a diagnostic method" (PDF). Journal of autism and developmental disorders 35 (6): 807–19. doi:10.1007/s10803-005-0026-5. PMID 16331530. - Mayes SD, Calhoun SL, Crites DL (2001). "Does DSM-IV Asperger's disorder exist?". Journal of abnormal child psychology 29 (3): 263–71. doi:10.1023/A:1010337916636. PMID 11411788. - Kopra K, von Wendt L, Nieminen–von Wendt T, Paavonen EJ (2008). "Comparison of diagnostic methods for Asperger syndrome". J Autism Dev Disord 38 (8): 1567–73. doi:10.1007/s10803-008-0537-y. PMID 18324466. - Szatmari P, White J, Merikangas KR (2007). "The use of genetic epidemiology to guide classification in child and adult psychopathology". Int Rev Psychiatry 19 (5): 483–96. doi:10.1080/09540260701563619. PMID 17896229. - Sanders JL (2009). "Qualitative or quantitative differences between Asperger's Disorder and autism? historical considerations". J Autism Dev Disord 39 (11): 1560–7. doi:10.1007/s10803-009-0798-0. PMID 19548078. - Witwer AN, Lecavalier L (2008). "Examining the validity of autism spectrum disorder subtypes". J Autism Dev Disord 38 (9): 1611–24. doi:10.1007/s10803-008-0541-2. PMID 18327636. - Willemsen-Swinkels SH, Buitelaar JK (2002). "The autistic spectrum: subgroups, boundaries, and treatment". Psychiatr Clin North Am 25 (4): 811–36. doi:10.1016/S0193-953X(02)00020-5. PMID 12462862. - Szatmari P (2000). "The classification of autism, Asperger's syndrome, and pervasive developmental disorder". Can J Psychiatry 45 (8): 731–38. PMID 11086556. - First MB (2008). "Autism and Other Pervasive Developmental Disorders Conference (February 3–5, 2008)". American Psychiatric Association. Retrieved 2008-10-29. - Reitzel J, Szatmari P. "Cognitive and academic problems." In: Prior M, editor. Learning and behavior problems in Asperger syndrome. New York: Guilford Press; 2003. p. 35–54, as cited in McPartland J, Klin A (2006), p. 774. - Klin A, Volkmar FR (2003). "Asperger syndrome: diagnosis and external validity". Child Adolesc Psychiatr Clin N Am 12 (1): 1–13. doi:10.1016/S1056-4993(02)00052-4. PMID 12512395. - Ghaziuddin M, Mountain-Kimchi K (2004). "Defining the intellectual profile of Asperger Syndrome: comparison with high-functioning autism". Journal of autism and developmental disorders 34 (3): 279–84. doi:10.1023/B:JADD.0000029550.19098.77. PMID 15264496.; Ehlers S, Nydén A, Gillberg C et al. (1997). "Asperger syndrome, autism and attention disorders: a comparative study of the cognitive profiles of 120 children". Journal of child psychology and psychiatry, and allied disciplines 38 (2): 207–17. doi:10.1111/j.1469-7610.1997.tb01855.x. PMID 9232467. as cited in McPartland J, Klin A (2006), p. 775. - Miller JN, Ozonoff S (2000). "The external validity of Asperger disorder: lack of evidence from the domain of neuropsychology". Journal of Abnormal Psychology 109 (2): 227–38. doi:10.1037/0021-843X.109.2.227. PMID 10895561. as cited in McPartland J, Klin A (2006), p. 775. - Wallis C (2009-11-02). "A Powerful Identity, a Vanishing Diagnosis". New York Times. - Medscape More Evidence DSM-5 May Significantly Reduce Autism Dx March 7, 2014 - U.S. Department of Health & Human Services Interagency Autism Coordinating Committee - Johnson CP, Myers SM, Council on Children with Disabilities (2007). "Identification and evaluation of children with autism spectrum disorders". Pediatrics 120 (5): 1183–215. doi:10.1542/peds.2007-2361. PMID 17967920. Lay summary – AAP (2007-10-29). Useful links for caregivers and clinicians working with a child with Asperger's. Parenting Asperger’s Community http://www.parentingaspergerscommunity.com/ Autism Society http://www.autism-society.org/about-autism/aspergers-syndrome/ Asperger’s Association of New England http://www.aane.org/ Autism Speaks http://www.autismspeaks.org/what-autism/asperger-syndrome OASIS @ MAAP (a complete outline of the diagnostic criteria referenced in this article) http://aspergersyndrome.org/Articles/The-Epidemiology-of-Asperger-Syndrome--A-Total-Pop.aspx	2	25	8	0	3	1	0.760751	12	6,067
ICD-10-CM Code F71 Moderate intellectual disabilities Billable CodeBillable codes are sufficient justification for admission to an acute care hospital when used a principal diagnosis. Mental Health CodeIndicates that the ICD code is referenced in DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Version 5) F71 is a billable ICD code used to specify a diagnosis of moderate intellectual disabilities. A 'billable code' is detailed enough to be used to specify a medical diagnosis. The ICD code F71 is used to code Intellectual disability Intellectual disability (ID), also called intellectual development disorder (IDD) or general learning disability, and formerly known as mental retardation (MR), is a generalized neurodevelopmental disorder characterized by significantly impaired intellectual and adaptive functioning. It is defined by an IQ score below 70 in addition to deficits in two or more adaptive behaviors that affect everyday, general living. Once focused almost entirely on cognition, the definition now includes both a component relating to mental functioning and one relating to individuals' functional skills in their environments. As a result of this focus on the person's abilities in practice, a person with an unusually low IQ may not be considered intellectually disabled. Intellectual disability is subdivided into syndromic intellectual disability, in which intellectual deficits associated with other medical and behavioral signs and symptoms are present, and non-syndromic intellectual disability, in which intellectual deficits appear without other abnormalities. Down syndrome and fragile X syndrome are examples of syndromic intellectual disabilities. \|MeSH Codes:\|\|D008607, D008607, D008607\| \|ICD 9 Codes:\|\|317, 318, 319\| Children with intellectual disabilities or other developmental conditions can compete in the Special Olympics. Coding Notes for F71 Info for medical coders on how to properly use this ICD-10 code Inclusion TermsInclusion Terms are a list of concepts for which a specific code is used. The list of Inclusion Terms is useful for determining the correct code in some cases, but the list is not necessarily exhaustive. - IQ level 35-40 to 50-55 - Moderate mental subnormality - DRG Group #884 - Organic disturbances and mental retardation. ICD-10-CM Alphabetical Index References for 'F71 - Moderate intellectual disabilities' The ICD-10-CM Alphabetical Index links the below-listed medical terms to the ICD code F71. Click on any term below to browse the alphabetical index. Equivalent ICD-9 Code GENERAL EQUIVALENCE MAPPINGS (GEM) This is the official exact match mapping between ICD9 and ICD10, as provided by the General Equivalency mapping crosswalk. This means that in all cases where the ICD9 code 318.0 was previously used, F71 is the appropriate modern ICD10 code.	4	2	0	0	0	12	0.804548	12	600
Table of Contents Bipolar disorder is a mental illness characterized by periods of mania and depression. The severity of the disorder can vary from person to person. Some people with bipolar disorder experience brief periods of mania or depression, while others may experience long periods of one or the other, or go through periods of both. The severity of the symptoms can also vary from person to person. Some people with bipolar disorder can function well with treatment, while others may experience more disabling symptoms. There is no one “bipolar disorder icd 9 code” that applies to all people with the disorder. However, there are several codes that may be used to describe the different types and severity of bipolar disorder. Bipolar Disorder, also known as manic-depressive illness, is assigned an ICD-9 code of 296.0x. This code is used by healthcare providers to classify and diagnose mental health conditions for the purpose of insurance reimbursement and medical record keeping. Bipolar Disorder is a mental illness characterized by extreme mood swings that can range from manic or hypomanic episodes to depressive episodes. The severity and frequency of these mood swings can vary from person to person. Treatment for Bipolar Disorder typically involves a combination of medication, psychotherapy, and lifestyle changes. Early diagnosis and treatment can help improve the symptoms and quality of life for those living with this condition. It’s important to work with a mental health professional to develop a comprehensive treatment plan that addresses your individual needs and goals. The bipolar disorder ICD 9 code is 296.0. What is the ICD-9 code for bipolar? The ICD-9 code 29680 for Bipolar disorder, unspecified is a medical classification as listed by WHO under the range -OTHER PSYCHOSES (295-299). This code is used to indicate a diagnosis of bipolar disorder when the specific type of bipolar disorder is not known. Bipolar I Disorder (BPI) is a mental illness that is characterized by extreme mood swings, from manic episodes of high energy and decreased need for sleep, to depressive episodes of low energy and increased need for sleep. People with BPI often have difficulty functioning in work and social settings. The exact cause of BPI is unknown, but it is believed to be a combination of genetic and environmental factors. Treatment for BPI typically includes a combination of medication and psychotherapy. What is the ICD-9 code for mood disorder Mood disorders, such as bipolar and depression, are classified under ICD-9 code. Anxiety disorders are classified under anxiety. Other disorders are classified under other. ICD-10 code F31 9 for Bipolar disorder, unspecified is a medical classification as listed by WHO under the range – Mental, Behavioral and Neurodevelopmental disorders. What are the 3 types of bipolar? Bipolar disorder is a serious mental illness that causes extreme mood swings. The three different diagnoses, bipolar I, bipolar II, and cyclothymic disorder, all involve different levels of severity and symptoms. People with bipolar disorder often experience periods of mania, where they feel excessively happy or energetic, and periods of depression, where they feel extremely sad or hopeless. Bipolar disorder can be very disruptive to a person’s life, and it can even lead to suicide. If you or someone you know is experiencing symptoms of bipolar disorder, it’s important to seek professional help. Bipolar disorder is a mental illness that is characterized by extreme mood swings. The four types of bipolar disorder are: Bipolar I, Bipolar II, Cyclothymic disorder, and Unspecified bipolar disorder. Bipolar I is the most common type of bipolar disorder and is characterized by extreme manic episodes followed by depressive episodes. Bipolar II is characterized by the shifting between the less severe hypomanic episodes and depressive episodes. Cyclothymic disorder is characterized by periods of hypomania and periods of depression. Unspecified bipolar disorder is characterized by symptoms that do not meet the criteria for any specific type of bipolar disorder. What is diagnosis code F31 62? The ICD-10 code F31.62 for Bipolar disorder, current episode mixed, moderate is a medical classification as listed by the World Health Organization (WHO) under the range of Mental, Behavioral and Neurodevelopmental disorders. This code is used to indicate a diagnosis of Bipolar disorder in patients who are currently experiencing a moderate episode that includes both manic and depressive symptoms. The ICD-10 code for schizophrenia is F20 9. This code is used to diagnose schizophrenia when the specific subtype of the disorder is not known. What is DX code F31 81 Bipolar II disorder is a mental disorder that is characterized by episodes of hypomania and major depression. The diagnostic code for bipolar II disorder is F3181. The disorder is considered mild in severity if the episodes of hypomania and depression are of short duration and do not significantly impair functioning. If the episodes are of long duration or are associated with significant impairment in functioning, the disorder is considered moderate or severe in severity. Unspecified bipolar disorder can be difficult to understand, especially if you’ve been diagnosed with it. The term itself is ambiguous, and it can be tough to know what it means for your mental health. However, it’s important to remember that the disorder is still serious and can cause problems in your life. If you’re struggling with unspecified bipolar disorder, reach out to a mental health professional for help. Is F32 9 a valid ICD-10 code? Major Depressive Disorder, Single Episode, Unspecified (ICD-10 code F32.9) is a mental disorder characterized by a single episode of major depression. The episode may be mild, moderate, or severe and can last for a period of two weeks to several months. Symptoms of major depression include depressed mood, loss of interest or pleasure in activities, weight loss or gain, insomnia or hypersomnia, fatigue, feelings of worthlessness or guilt, impaired concentration, and thoughts of death or suicide. The ICD-9-CM is the official system of assigning codes to diagnoses and procedures associated with hospital utilization in the United States. The ICD-9 was used to code and classify mortality data from death certificates until 1999, when use of ICD-10 for mortality coding started. What is the new word for bipolar Bipolar disorder is a serious mental illness that causes unusual shifts in mood, energy, activity levels, and the ability to carry out day-to-day tasks. The disorder can be very debilitating, and people with bipolar disorder often have difficulty functioning in their daily lives. There is no single cause of bipolar disorder, but it is believed to be caused by a combination of genetic and environmental factors. Treatment for bipolar disorder typically includes medication and psychotherapy. Bipolar disorder is a mental illness that is characterized by extreme swings in mood and energy levels. While mania – a state of abnormally elevated mood and energy – is a defining feature of bipolar disorder, other conditions can also cause manic-like symptoms. These include organic mood disorders such as endocrine or metabolic conditions, drug intoxications, and tumors. Secondary mania refers to mania that occurs in the context of substance abuse. making a differential diagnosis can be difficult, but it is important to correctly identify the cause of the manic symptoms in order to provide the most effective treatment. Is bipolar disorder a DSM-5 diagnosis? Bipolar disorder is a mental illness that causes people to experience extreme changes in mood. These changes can be very debilitating and make it difficult for people to function in their everyday lives. Bipolar disorder is often treated with medication and therapy. Bipolar disorder is a mental health condition that is characterized by extreme mood swings. These can range from feeling extremely happy and energetic to feeling completely hopeless and down. Other symptoms of bipolar disorder can include difficulty concentrating, loss of interest in everyday activities, and feelings of guilt and despair. If you are experiencing any of these symptoms, it is important to reach out to a mental health professional for help. What is the most severe bipolar diagnosis Bipolar I disorder is the most severe form of the illness, characterized by manic episodes that can last for days or even weeks. These episodes can be so severe that they lead to hospitalization. Bipolar II disorder is characterized by predominantly depressive episodes accompanied by occasional hypomanic episodes. Hypomanic episodes are milder than manic episodes but can still impair functioning. Bipolar disorder is a mental illness that is characterized by extreme mood swings. A person with bipolar disorder may have periods of mania, where they feel extremely happy and energized, followed by periods of depression, where they feel extremely sad and low. In order to diagnose bipolar disorder, a doctor will perform a physical exam, ask about your symptoms, and recommend blood testing to determine if another condition, such as hypothyroidism, is causing your symptoms. If the doctor does not find an underlying cause of your symptoms, he or she will perform a psychological evaluation. What are 3 symptoms of bipolar Bipolar disorder is a mental illness that can cause your mood to swing from an extreme high to an extreme low. Manic symptoms can include increased energy, excitement, impulsive behaviour, and agitation. Depressive symptoms can include lack of energy, feeling worthless, low self-esteem and suicidal thoughts. If you are experiencing any of these symptoms, it is important to seek professional help. Signs of bipolar disorder can vary from person to person, but there are some common signs that are generally associated with the condition. These can include feeling overly happy or “high” for long periods of time, feeling jumpy or “wired”, having a reduced need for sleep, talking very fast with racing thoughts and rapid changes of topic, feeling extremely restless or impulsive, and becoming easily distracted. If you or someone you know is exhibiting these symptoms, it is important to seek professional help in order to get an accurate diagnosis and proper treatment. What can trigger a manic episode Hypomania or mania can be caused by a variety of factors, including high levels of stress, changes in sleep patterns, lack of sleep, use of recreational drugs or alcohol, and seasonal changes. Some people may be more susceptible to hypomania or mania in certain seasons, such as spring. This diagnosis is given to someone who is currently experiencing a manic episode, but does not have any psychotic symptoms. “Living with Bipolar Disorder: My Journey and Tips for Making Life Easier” Hi, I’m a person living with Bipolar Disorder (ICD-9 code 296.0x). When I was first diagnosed, I felt overwhelmed and unsure of what the future would hold. But with time, support, and the right resources, I have learned how to manage my condition and live a happy and fulfilling life. In this article, I want to share my personal journey and the tips that have made a real difference in my life. When I was first diagnosed with Bipolar Disorder, I was in a manic episode and struggling with high energy and racing thoughts. It was a confusing and overwhelming time for me, but with the help of my doctor, family, and friends, I was able to get the help I needed. Here are my top three tips for making life easier with Bipolar Disorder: Stay on top of your medications: Taking my medication as prescribed by my doctor has been key in managing my symptoms and maintaining stability. It’s important to be consistent with your medications and to communicate any concerns or side effects to your doctor. Maintain a stable routine: Having a stable routine and structure in my life has been essential in managing my condition. I make sure to keep a consistent sleep schedule, eat healthy, and engage in regular physical activity. Connect with a support system: Having a strong support system is crucial when living with a mental illness. I have found it helpful to connect with others who understand what I’m going through, whether it be through a support group, therapy, or simply talking to friends and family. In conclusion, living with Bipolar Disorder can be challenging, but with the right support and resources, it’s possible to live a happy and fulfilling life. By staying on top of your medications, maintaining a stable routine, and connecting with a support system, you can make life easier with this condition. Don’t give up hope, and remember that you’re not alone. The ICD-9 code for bipolar disorder is 296.0. Although there is not currently a cure for bipolar disorder, treatment is available that can help people manage the symptoms and lead relatively normal lives. With proper treatment, many people with bipolar disorder are able to maintain gainful employment and support their families. If you or someone you know is struggling with bipolar disorder, don’t hesitate to reach out for help. What is Bipolar Disorder? Bipolar Disorder is a mental health condition characterized by extreme mood swings, ranging from depressive episodes to manic episodes. These mood swings can last for several days or weeks and can interfere with a person’s daily life and relationships. What is the ICD-9 Code for Bipolar Disorder? The ICD-9 code for Bipolar Disorder is 296.0-296.9. What are the Symptoms of Bipolar Disorder? Symptoms of Bipolar Disorder can vary, but typically include extreme changes in mood, energy levels, and behavior. During a manic episode, a person may feel extremely euphoric, have increased energy and little need for sleep, and engage in impulsive or risky behaviors. During a depressive episode, a person may feel extremely sad, have low energy levels, and experience difficulty with daily activities. How is Bipolar Disorder Diagnosed? Bipolar Disorder is diagnosed based on a person’s symptoms, medical history, and the results of a mental health evaluation. A healthcare provider may also use diagnostic tools, such as the Mood Disorder Questionnaire, to assist with the diagnosis. How is Bipolar Disorder Treated? Bipolar Disorder is treated using a combination of medication and therapy. Mood stabilizing medication, such as lithium, is commonly used to treat bipolar disorder, while antipsychotics may be used to treat manic symptoms. Therapy, such as cognitive behavioral therapy, can also be helpful in managing symptoms and improving overall functioning. Can Bipolar Disorder be Cured? Bipolar Disorder is a chronic condition that cannot be cured. However, with proper treatment and support, many people with Bipolar Disorder are able to manage their symptoms and lead fulfilling lives. What is the Prognosis for People with Bipolar Disorder? The prognosis for people with Bipolar Disorder can vary. With proper treatment and support, many people are able to manage their symptoms and improve their overall quality of life. However, some people may experience frequent relapses or may struggle with symptoms throughout their lives.	4	3	2	0	1	13	0.986533	16	3,072
Asthma and COPD are two chronic conditions common enough in the general population that most physicians will want to know the documentation needs for coding in ICD-10. I’ll compare them to documentation for ICD-9. Asthma coding has changed. Two axes of classification that physicians rarely documented in ICD-9 have been eliminated, and two axes of classification (that hopefully physicians will find useful) have been added in ICD-10. As a result, the total number of asthma and COPD codes is roughly the same in ICD-9 and ICD-10 -- 17 ICD-9 codes and 20 ICD-10 codes. Here are the two hair-splitting ICD-9 axes of classification that have been eliminated in ICD-10: - ICD-10 does not force physicians to categorize asthma as intrinsic or extrinsic. Asthma is just asthma. - ICD-10 does not have separate codes for chronic obstructive asthma, as opposed to chronic obstructive bronchitis or plain old chronic obstructive pulmonary disease. COPD is just COPD in ICD-10. More about COPD when we finish with asthma. Here are the two (hopefully more useful) axes of classification for asthma that have been added to ICD-10: - Asthma is categorized by degree of severity — mild, moderate and severe are the terms used in the codes to distinguish the level of severity. - Asthma is further categorized as either intermittent or persistent. (Intermittent often means the asthma has an external trigger; therefore, extrinsic/allergic in its cause. But it doesn’t rule out non-allergic asthma that is also intermittent. Let’s face it, asthma causes are not that easy to pin down, and having the classification hinge on the physician’s ability to use mutually exclusive terminology to declare the cause of the asthma doesn’t make sense. It is probably in your interest to use the ICD-10 terminology in documenting a patient encounter. Unlike the discontinued detail in ICD-9, the ICD-10 codes clearly distinguish the behavior of an illness rather than its cause. They tell how sick a patient is, and therefore how much effort is involved in monitoring and treatment. A patient with severe persistent asthma is clearly distinguishable from a patient with mild persistent asthma. And eventually, if not immediately, those distinctions are going to be used by the (evil) people who use diagnosis codes to calculate what to pay you and to comment on how well you do your job. You of course have the right to vote against the entire ICD system by not documenting to comply with measures of clinical significance cooked up by a global committee, but at some point it may, literally, cost you. These clinical distinctions will no doubt be used wherever possible to fine-tune payment systems and quality report cards and all the rest of it. It is no secret that the healthcare system is not optimized for the physician’s convenience or preferences on how to best deliver care, but by being a practicing physician in the United States you are playing this game, which includes using ICD codes to eke out all the justifiable credit you can for the work you do. As an example, here are the ICD-10 asthma codes for a patient with severe persistent asthma, with the ICD-9 codes they replace. J45.50 Severe persistent asthma, uncomplicated 493.00 Extrinsic asthma, unspecified 493.10 Intrinsic asthma, unspecified J45.51 Severe persistent asthma with (acute) exacerbation 493.02 Extrinsic asthma with (acute) exacerbation 493.12 Intrinsic asthma with (acute) exacerbation J45.52 Severe persistent asthma with status asthmaticus 493.01 Extrinsic asthma with status asthmaticus 493.11 Intrinsic asthma with status asthmaticus Notice you still have the ability to capture acute exacerbation and status asthmaticus. The same is true of all the flavors of asthma mentioned earlier -- severe intermittent, moderate persistent, moderate intermittent, etc. The whole category is perfectly regular. There is also an unspecified subcategory if you choose not to play the documentation game. If you document only “patient is on prescribed inhalers for asthma” the default code is J45.909 Unspecified asthma, uncomplicated Not a lot to say about COPD beyond what I mentioned earlier. As with asthma coding, an axis of classification that wasn’t seen as useful was eliminated. ICD-10 added a code for a common acute exacerbation that brings a patient with COPD back to seek care — COPD with acute lower respiratory infection such as acute bronchitis or pneumonia. The specific pneumonia or bronchitis code can be coded in addition. J44.0 Chronic obstructive pulmonary disease with acute lower respiratory infection As with ICD-9, there is an ICD-10 code for COPD with exacerbation, which captures “decompensated” COPD, without any additional documentation. J44.1 Chronic obstructive pulmonary disease with (acute) exacerbation 491.21 Obstructive chronic bronchitis with (acute) exacerbation 493.22 Chronic obstructive asthma with (acute) exacerbation And of course there is an unspecified option, which no longer splits hairs about whether the COPD is predominantly asthma or predominantly bronchitis — it’s just COPD. J44.9 Chronic obstructive pulmonary disease, unspecified 491.20 Obstructive chronic bronchitis without exacerbation 493.20 Chronic obstructive asthma, unspecified 496 Chronic airway obstruction, not elsewhere classified Getting rid of dead wood in the classification is one of the benefits of these periodic revisions of the ICD. In the case of asthma and COPD, distinctions of dubious relevance have been abandoned. Even if you could say with absolute certainty that the cause of the patient’s asthma is extrinsic, the fact remains that regardless of the cause there is constriction of airways and inflammation in the lungs that must be treated. Instead of forcing you to declare the underlying cause, the ICD-10 asthma codes give a clearer indication how sick the patient is and therefore supports what you did to treat that patient. Rhonda Butler is a senior clinical research analyst with 3M Health Information Systems. She is responsible for the development and maintenance of the ICD-10 Procedure Coding System since 2003 under contract to CMS, and for the development and maintenance of the ICD-10 General Equivalence Mappings (GEMs) and Reimbursement Mappings under contract to CMS and the CDC. She leads the 3M test project to convert the MS-DRGs to ICD-10 for CMS, and is on the team to convert 3M APR-DRGs to ICD-10. Rhonda also writes for the 3M Health Information Systems blog.	4	4	0	0	0	9	0.556749	9	1,470
This information is provided to broaden the understanding of chiropractic and health care in general. The following are research and facts both: “Chiropractic is a health care discipline which emphasizes the inherent recuperative power of the body to heal itself without the use of drugs or surgery. The practice of chiropractic focuses on the relationship between structure (primarily the spine) and function (as coordinated by the nervous system) and how that relationship affects the preservation and restoration of health. In addition, Doctors of Chiropractic recognize the value and responsibility of working in cooperation with other health care practitioners when in the best interest of the patient.” “The principle of chiropractic is that the body’s innate recuperative power is affected by and integrated through the nervous system.” The practice of chiropractic includes establishing a diagnosis; facilitating neurological and biomechanical integrity through appropriate chiropractic case management; and advising and educating patients on spinal hygiene, rehabilitative exercise, nutrition, and healthful living practices. “A subluxation is a complex of functional and/or structural and/or pathological articular changes that compromise neural integrity and may influence organ system function and general health. A subluxation is evaluated, diagnosed,and managed through the use of chiropractic procedures based on the bes available rational and empirical evidence.” The Association of Chiropractic Colleges, Position Paper Practice chiropractic includes the diagnosing and locating of misaligned or displaced vertebrae and, through the manual manipulation and adjustments of the spine and other skeletal structures, treating disorders of the human body. 1. To earn a Doctor of Chiropractic degree the candidate must complete a four year program consisting of 4800 hours of classroom, laboratory, and clinical study, including anatomy, physiology, chiropractic technique, radiology, biochemistry, toxicology, biomechanics, nutrition, diagnosis and physical examination, and a clinical internship consisting of one year of hands on clinical experience and training in a professional clinical setting. The CCE is officially recognized as an accredition agency by the US Department of Education. The CCE is a member of the Council on Post-Secondary Accreditation (COPA) and the Coucil of Specialized Accrediting Agencies (CSSA). 2. The D.C. must obtain a state license through examination before receiving the privilege of practice. 3. All 50 states, the District of Columbia, U.S. Virgin Islands, and Puerto Rico license doctors of Chiropractic. All these jurisdictions include Chiropractic health care in their workers’ compensation statutes. 4. Chiropractic services are included in Medicare, the Vocational Rehabilitation Act, Federal Workers’ Compensation laws, most Federal Employees’ Benefits programs, the Railroad Retirement Act, and the Longshoremen’s & Harbor Workers’ compensation Act. 5. In the private sector, virtually all commercial insurance carriers include Chiropractic services in their health plans. 6. The National Conference of Insurance Legislators adopted a model; bill for state health-insurance programs that defines “physician” to include the doctor of Chiropractic. 7. The Department of Health and Human Services classifies doctors of Chiropractic as category 1 providers, just like medical doctors, osteopaths, and dentists. 8. The U.S. Public Health Service classifies doctors of Chiropractic among “medical specialists and practitioners.” 9. Chiropractic is the third largest health care profession in the Western world behind medicine and dentistry. 10. 94% of the spinal manipulation done in the U.S. is done by chiropractors. Chiropractic care is not only effective but has been documented as superior in many areas of health care. It is significant to note that almost all of the following studies were performed by M.D.’s. 1. One of Chicago’s leading medical orthopedists testified about the results he had noticed between two competing hospitals in Chicago, one which was using doctors of Chiropractic and one which was not. Since he was on the staff of both hospitals he could evaluate the results of each. He found that the hospital using Chiropractic care was sending patients home 7 to 9 days sooner and that the reason was entirely due to the Chiropractic care that they were receiving. Per Freitag, MD,PhD, US Federal Court Testimony, Chicago, IL., May, 1987. Comparing JFK Hospital with Lutheran General Hospital, which does not use Chiropractic. 2. AV MED, the largest HMO in the southeastern U.S., tried an experiment with 100 of its medically unresponsive patients by sending them to a local doctor of Chiropractic. Within 3 weeks 86% of them had their ailments corrected. 12 of these cases were medically diagnosed as needing disc surgery. All 12 of these cases ere corrected and none needed surgery. Just these 12 cases saved the HMO $250,000 in surgical/hospital bills. Later re-evaluation of these cases showed that the results were permanent Herbert Davis, MD, AVMED Health Maintenance Organization, Miami, FL. 1982 3. In 1979, the Royal Commission of Inquiry on Chiropractic in New Zealand, after an 18 month study in five nations, including the U.S., concluded, “The Commission has found it established beyond any reasonable degree of doubt that chiropractors have a more thorough training in spinal mechanics and spinal manual therapy than any other health professional.” It found that Chiropractic was a scientifically based, valid, safe and very effective treatment that should be in the mainstream of health care and should be used in hospitals. Chiropractic in New Zealand-Report of the Commission of Inquiry, 1979 4. In 1971, the Oregon Workers’ Compensation Study showed that people under Chiropractic care were able to return to work in half the time as those receiving medical care. Also that chiropractic costs were less than 25% of medical costs. 5. In 1972, the California Workers’ Compensation Study comparing Chiropractic to medical care for back ailments on 1000 patients showed that Chiropractic was twice as effective and the patients lost half as many days as of work. Richard Wolf, MD, California Workers Compensation Records, 1972 6. In 1986 the Florida Workers’ Compensation Study the duration of disability was 51.3% shorter for chiropractic patients. The cost of chiropractic care was 58.8% less than medical care. 7. The recent Utah Workers’ Compensation Study followed 3062 cases. The record shows that Chiropractic care outperformed medicine by 10:1 margin in compensation costs. Kelly Jarivs, DC. Red Philips, DC, Elliot Morris, JD MBA Workers Compensation Fund of Utah, 1991. 8. A two year study conducted by the Italian government followed 17,000 patients. The dramatic results showed that patients under chiropractic care had their hospitalization for back ailments reduced by 87.6% and work loss by 75.5% Prof.F.Splendori, Chiropractic Therapeutic Effectiveness-Social Importance. Incidence on Absence from Work and Hospitalization. Italy 9. A ten year government study in Great Britain showed that among all patients with severe and chronic pain, chiropractic patients improved 13% more than medical patients. “If all the patients were referred for chiropractic instead of hospital treatments…there might be a reduction of some 290,000 days in sickness absence during two years saving about $21,580,000 in output and $4,814,000 in social security payments.” T.W. Mead, FRCP, British Medical Research Council, 1990 10. In 1991, the RAND study from UCLA found Chiropractic care to be an “appropriate” treatment for low back disorders. Shekelle PG, Adams et el. The Appropriateness of Spinal Manipulation for Low Back Pain:Indications and Ratings by a Multidisciplinary Expert Panel. RAND Corporation, Santa Monica, California 11. Kirkaldy-Willis, M.D., world renowned medical orthopedist, joined David Cassidy, D.C., PhD. to do an evaluation of the clinical results of Chiropractic care on evaluation of the clinical results of Chiropractic care on 171 chronic medically unresponsive low back sufferers for a period of 7 years. Within 3 weeks, Dr. Cassidy eliminated 87% of the ailments. It is significant to note that a reevaluation of these patients one y ear later showed that they remained pain free! David Cassidy, DC, Kirkaldy Willis, MD, University of Saskatchewan, 1985 12. A study conducted during WWII by a former AMA (American Medical Association) trustee reported to the AMA the impressive results a doctor of Chiropractic had in the Army medical ward and that his over-all results compared with the best that the department had to offer. The study was suppressed for over 40 years until the Wilk, et. al. v. AMA trial. 13. There are more controlled studies showing the effectiveness of manipulation for low back pain compared to any other type of treatment for low back pain. 14. In 1991 a Gallop Poll revealed that 90% of Chiropractic users felt their treatment was effective. A report in the Western Journal Of Medicine (March, 1989) stated that patients of Chiropractors were 3 times more satisfied with their care than patients of family practice medical doctors. 15. The Ontario government commissioned a study on Chiropractic that analyzed all available clinical studies, statistics and other pertinent data and found that there was an “overwhelming body of evidence” that Chiropractic was superior, more therapeutically effective, cost efficient, safer, more scientifically based and had a much higher level of patient satisfaction than Medical care. It cautioned the Ontario government against many of the “untested, questionable or harmful medical treatments” and urged the government to prefer Chiropractic care over Medical care for some ailments. It also recommended that Chiropractors be “gate keepers” in hospitals when admitting back ailments. Manga Report to the Ontario Ministry of Health, August, 1993. Research Affirms the Foundations of Chiropractic Tooth decay occurs well before you get the first warning signs of pain. That is why the dental profession recommends regular check-ups which include teeth cleaning and gum care as well as the regular home care of brushing and flossing teeth. Wear and tear of the engine in a car will occurs well before the oil runs out, but everyone knows to change the oil every three thousand miles. “Similarly, according to chiropractic theory and practice, vertebral subluxation [the area of the spine or other joint which is stuck and needs to be adjusted] may have a significant impact on health before the appearance of pain or other signs and symptoms. For example, loss of movement or stiffness in a spinal joint may lead to associated degenerative changes [osteoarthritis] – changes that can be prevented or even reversed if there is timely treatment to restore movement in the joint, but that may be irreversible before warning signs of pain appear.” In several experiments, the knee joints of rabbits were immobilized [splinted so they could not bend] for 16 weeks. Within ONE WEEK degenerative changes began to occur and by week 12 the joints were completely fused. The follow-up experiment was even more interesting. In one group of rabbits which were immobilized for five weeks, the splints were then removed. Over the next 18 months, some were released to “normal cage activity” and some jogged on a treadmill five days per week. The rabbits in both of these groups had NO increase in the level of osteoarthritis once they resumed regular activity. So what’s the bottom line: Loss of movement in a joint leads to significant degeneration (arthritis) and this may happen well before symptoms occur. Timely restoration of this movement by chiropractic adjustments and regular exercise will prevent, halt and may reverse these degenerative changes. From The Chiropractic Report, May 2004, p.1 Just as Chiropractic’s effectiveness has been studied so has its safety. Chiropractic’s approach is drug-free and non-surgical, therefore eliminating two of the largest risk factors in the health care field. Reports of danger are grossly exaggerated. Much misinformation and misunderstanding of the safety issue has been propagated by the (AMA) American Medical Association. In the early 1960′s, the AMA decided to try to contain and eliminate Chiropractic as a profession. The AMA’s purpose was to prevent medical physicians from referring patients to Chiropractors and accepting referrals of patients from Chiropractors; to prevent Chiropractors from obtaining access to hospital diagnostic services; to prevent medical physicians from teaching at chiropractic colleges or engaging in any joint research; and to prevent any cooperation between the two groups. The AMA unfairly told its membership, medical students, insurance companies and the general public that Chiropractic was an unscientific cult. Once some of the AMA’s policies became publicly known they stopped some of their overt actions. In 1976, five Chiropractors filed a lawsuit against the AMA for violation of the Sherman Anti-trust Law. After almost 15 years of vigorous litigation, the U.S. Court of Appeals stated that the AMA intended to “destroy a competitor,” and that there was evidence “showing that the AMA was motivated by economic concerns.” The court found that the AMA had concealed evidence showing its guilt and was caught “doctoring” documents. The AMA was “guilty of systematic, long term wrong doing and has not acknowledged its lawlessness.” So, is Chiropractic safe? A number of literature reviews of serious occurrences from chiropractic adjustments have been documented. The most exhaustive study discussed 113 cases of vertebro-basilar accidents following spinal manipulative therapy, from 1934 to 1987, a period of 53 years. Of the cases documented 66 were chiropractic, 18 medical, 9 osteopathic, 2 physical therapist and the remaining 13 were divided between “wife,” “self,” and “unknown”. Let’s put these numbers in perspective. There were 66 chiropractic cases in 53 years; a little more than one per year. There are currently about 52,000 chiropractors in practice treating, on average, about 100 patients per week. That works out to 5.2 million adjustments per week or 286 million adjustments per year. This works out to 1 to 2 cases of stroke, paralysis or death per 286 million adjustments. One author, a medical doctor, stated about manipulation in general, “there is probably less than one death of this nature out of several tens-of-millions of manipulations.” Some medical authors state that the risk of manipulation to the neck is 0.0002% or 2-3 cases per million. No matter how one interprets the results, more people die from complications of drugs and surgery in one single afternoon than in 20 years of cervical adjustments. As a comparison to the risk of manipulation, the risk of death from surgery to the cervical spine is 700 per million. From 1947-1978 in cases of stroke related death following manipulation, 9/10 death were attributed to manipulation by MD, DO or PT. See the links below for more information: - A review of studies involving chiropractic adjustments and stroke - Chiropractic and the Risk of Stroke - What are the Risks of Chiropractic Neck Adjustments “Researchers studying health-care quality have concluded that medical injuries caused during hospital stays kill tens of thousands of American patients annually, requireing at least 2.4 million extra hospital days resulting in potential medical charges of $9.3 billion.” Wall Street Journal 10/08/03 p. A3 To put chiropractic safety in perspective here are some facts about medical care: 1. A Yale New Haven hospital study showed that 100,000 to 200,000 people die per year from medication reactions. A Johns Hopkins study found that 14% of hospital stays are extended because of medication reactions. 2. A multi-hospital study found nearly 1000 people die every week from UNNECESSARY surgery. 3. When medical doctors went on strike for one month in Los Angles County, the death rate dropped by 153 persons based on state records. 4. A Harvard University study showed that in one year medical negligence caused 7000 hospital deaths in New York state. 5. The U.S. Office of Public Health found that 2/3′s of the over-the-counter drugs do NOT do what the companies promise. 6. On August 26, 1992 the Food and Drug Administration said that 415 ingredients in over-the-counter drugs DO NOT WORK! 7. 1.5 million people/yr will be hospitalized with iatrogenic reactions ACA 10/95 8. 100,000 people will die/yr due to iatrogenic reactions ACA 10/95 9. 52,000 people/yr die from complications of unnecessary surgery ACA 10/95 10. 1600 children die/yr due to allergic reactions to aspirin ACA 10/95 11. 300/yr die from flying commercial airlines ACA 10/95 12. Advisors to the FDA are expressing concern over signs that many popular non-steroidal anti-inflammatory drugs (NSAIDS) are more dangerous than doctors and the public think. Forty-one thousand hospitalizations and 3300 deaths each year are blamed on such side effects. According to the FDA, 299 American deaths have been linked to Feldene (piroxicam) since 1982. (Associated Press 10/11/95) 13. Adverse reactions to prescribed drugs now cost the US $76 billion annually. 8.7 million hospital admissions per year. (Associated Press 10/2/95) - ACA 10/95 - Small intestine surgeries 1 in 4.76 - Colon surgeries 1 in 14 - Spinal fusion 1 in 51 - Appendectomies 1 in 74 - Cholecystectomy 1 in 100 - Laminectomies 1 in 204 - Coronary arteriography 1 in 222 Deaths per year from GI bleeding due to anti-inflammatory drugs for osteoarthritis- 400 per 1 million. 16,500 deaths per year (Wolfe MM, Lichtenstein DR, Singh G Gastrointestinal toxicity of non-steroidal anti-inflammatory drugs. New England Journal of Medicine, 1999: 340(24): 1888-1899. Out of every 100,000 women under 40 who take birth control pills, 28 of them will suffer a stroke> JCAHO Documents Alarming Increase in Surgical Mistakes in US WESTPORT, CT (Reuters Health) Dec 05 – Since 1998, the number of operations performed on wrong surgical sites or wrong patients has increased dramatically in the US, according to a report released Wednesday by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). In 1998, the JCAHO issued a Sentinel Event Alert after 15 “wrong site” surgery cases were reported to the organization. By the time the current report was released this number had skyrocketed to 150. Orthopedic/podiatric operations were the most common procedures linked to errors, accounting for 41% of the 126 cases that were analyzed. General surgery procedures accounted for 20% of the cases, neurosurgery operations for 14%, and urologic surgery operations for 11%. The remaining cases involved other procedures such as dental/oral maxillofacial operations. Fifty-eight percent of cases occurred in an ambulatory surgical setting, 29% in the inpatient operating room, and 13% in other inpatient settings. Most of the errors involved operations on wrong body parts or sites, but 13% involved operations on the wrong patient and 11% involved the wrong surgical procedure. The JCAHO identified a number of factors that seemed to increase the risk of surgical mistakes. Among these, emergency status of the case and unusual patient physical characteristics were the most commonly cited. In addition, most cases involved a breakdown in communication between surgical team members and the patient or the patient’s family. “Although the wrong site surgery problem has been addressed on a local level in many areas of the country, there has been no organized national effort to eliminate wrong site surgery,” Dr. S. Terry Canale, immediate past president of the American Academy of Orthopaedic Surgeons, said in a statement. In the report, the JCAHO makes several recommendations to eliminate surgical mistakes: Mark the surgical site and involve the patient in the process. Create and use verification checklists. Before operating, verify with each team member the patient’s identity, the surgical site, and the procedure being performed. Take a “time out” in the operating room to check one last time that the correct procedure is being performed on the correct patient at the correct site. Monitor compliance with these procedures. In 1993, for the first time in history, Congress authorized $1.8 million in Chiropractic research. $750,000 was allocated for research studies at chiropractic colleges involving the collaboration of doctors of chiropractic and medical doctors. The other section of the bill allocates an additional $1 million in funding to increase the chiropractic profession’s ability to assist in medically underserved rural areas. (Pub. Law 103-112) Acute Low Back Problems in Adults- U.S. Department of Health and Human Services Chiropractic manipulation was recommended as a treatment of choice for acute low back pain by the Agency For Health Care Policy and Research, a division of the Department of Health and Human Services. These guidelines were published in December, 1994. Independent research authorities such as RAND Corporation, which reported in 1991 that spinal manipulation was now proven to be an appropriate treatment for most back pain patients. Shekelle, PG, Adams, A, et al. The Appropriateness of Spinal Manipulation for Low-Back Pain. RAND Corporation, Santa Monica, CA, 1992. * Worker’s Compensation studies suggest a minimum 50% saving in overall costs when treatment is chiropractic rather than medical. California, 1972: Half the work days were lost by chiropractic patients as compared to medical patients. Wolf, CR, (1974), Industrial Back Injury. Internation Review of Chiropractic, 26:6-7. Wisconsin, 1978: Half the work days were lost by chiropractic patients as compared to medical patients. Chiropractic care about half the cost of medical care. Duffy, DJ, (1978), A Study of Wisconsin Industrial Back Injury Cases, University of Wisconsin, unpublished monograph. Florida, 1986: The duration of disability was 51.3% shorter for chiropractic patients. The cost of chiropractic care was 58.8% less than medical care. Wolk,S (1988), An Analysis of Florida Workers’ Compensation Medical Claims for Back Related injuries, Foundation for Chiropractic Education and Research, Arlington, VA. Utah, 1991: Chiropractic care outperformed medical care by a 10:1 margin in compensation costs. The number of work days lost under medical care was nearly 10 times higher than those receiving chiropractic care. Jarvis KB, Phillips RD et al (1991), Cost Per Case Comparison of Back Injury Claims of Chiropractic versus Medical Management for Conditions with Identical Diagnostic Codes, Journal of Occupational Medicine, 33(8): 847-852. The Meade Study A ten year government study in Great Britain showed that among all patients with severe and chronic pain, chiropractic patients improved more than medical patients. “If all the patients were referred for chiropractic instead of hospital treatments…there might be a reduction of some 290,000 days in sickness absence during two years saving about $21,580,000 in output and $4,814,000 in social security payments.” “…for patients with low back pain in whom manipulation is not contraindicated chiropractic almost certainly offers worthwhile, long term benefit in comparison with hospital outpatient management.” Meade, TW, Dyer, S, et al. Low Back Pain of Mechanical Origin: Randomized Comparison of Chiropractic and hospital Outpatient Treatment, British Medical Journal, 2 June 1990, Vol.300, No.67137, pp. 1431-1437. The Meade Study- Follow-up The author did a three-year follow-up to the study which concluded that, “When chiropractic or hospital therapists treat patients with low-back pain as they would in day-to- day practice,those threated by chiropractic derive more benefit and long term satisfaction than those treated by hospitals.” There was a 29% hreater improvement in patients treated with chiropractic compared with hospital care. Meade, TW Randomized Comparison of Chiropractic and Hospital Outpatient Management for Low Back Pain: Results from an Extended Follow-up, British Medical Journal, 5 August 1995, Vol.311. The Duke Study Based on a literature review of several headache treatment options, a panel of 19 multidisciplinary experts concluded that spinal manipulations resulted in almost immediate improvement for cervicogenic headaches and had significantly fewer side effects and longer-lasting relief of tension-type headache than a commonly-prescribed medication. Researchers concluded the following: Manipulation appeared to result in immediate improvement in headache severity when used to treat episodes of cervicogenic haedache when compared with an attention-placebo control. Furthermore, when compared to soft-tissue therapies (massage), a course of manipulation treatments resulted in sustained improvement in headache frequency and severity.” McCrory DC, it al. Evidence Report: Behavioral and Physical treatments for Tension-type and Cervicogenic Headache. Duke University Evidence-Based Practice Center, Durham, North Carolina, January, 2001. In 1991, a Gallop Poll revealed that 90% of chiropractic patients felt their treatment was effective. A report in the Western Journal of Medicine in 1989 stated that patients of chiropractors were 3 times more satisfied with their care than patients of family practice medical doctors. Demographic Characteristics of Users of Chiropractic Services. The Gallup Organization, Princeton, N.J., 1991. Back Pain Care from Family Physicians and Chiropractors, Western Journal of Medicine, March 1989, Vol.150, pp. 351-355. * The Manga Report, commissioned by the government of Ontario, Canada, in 1993, stated that chiropractic management is superior to medical management for patients with low-back pain – in terms of safety, scientific evidence of effectiveness, evidence of cost-effectiveness and patient satisfaction. “There is an overwhelming body of evidence indicating that chiropractic management of low-back pain is more cost-effective than medical management.” “Chiropractic services should be fully integrated into the health care system.” “There should be a shift in policy to encourage and prefer chiropractic services for most patients with low back pain.” “Finally, the government should take all reasonable steps to actively encourage cooperation between providers, particularly the chiropractic, medical and physiotherapy professions. Lack of cooperation has been a major factor in the current inefficient management of low back pain. Better cooperation is important if the government is to capture the large potential savings in question and, it should be noted, is desired by an increasing number of individuals within each of the professions. Manga P, Angus, D it al (1993) “The Effective and Cost-Effectiveness of Chiropractic Management of Low-Back Pain,” Pran Manga and Associates, University of Ottawa, Canada. * The Virginia Assessment “The researchers conducted a through investigation between chiropractic and traditional medical treatment. The evidence shows that chiropractic care provides substantial benefits at a relatively low cost. They concluded that adding chiropractic benefits would have a very small impact on health insurance expenditures and might actually lower overall health care costs.” Schifrin, Leonard G. (1992), Chancellor Professor of Economics and Preventive Medicine, The College of William and Mary, Williamsburg, Va. * University of Richmond Research “Researchers compared chiropractic care with treatment rendered by general practitioners, internists, surgeons, physicians, and non-physicians. When the treatment costs were compared, chiropractic care was the lowest. Total treatment costs were lower for those receiving chiropractic care, than for those receiving care from other types of practitioners. Researchers concluded that if chiropractic care was covered by insurance to the degree of other types of care, it would be the first choice by many patients.” Dean, David H., Ph.D., Schmidt, Robert M., Ph.D., A Comparison of the Costs of Chiropractors Versus Alternative Medical Practitioners, Bureau of Disability Economics Research, Robins School of Business, University of Richmond, January 13, 1992, Page 25. * The New Zealand Report “In 1979, the government of New Zealand published an objective study of chiropractic. The commission concluded that spinal adjustments given by registered chiropractic doctors are safe, and that their education helps them assess and manage spinal problems at a very high level. Based upon the commission’s objective findings, chiropractic care was recommended to be a covered service under its Social Security and Accident Compensation Acts.” Chiropractic in New Zealand, Report of the Commission of Inquiry, 1979, Page 78.s * The Colic Study When researchers compared spinal manipulation for the treatment of infantile colic to dimethicone (a medication for colic), they came to a simple conclusion: “Spinal manipulation is effective in relieving infantile colic.” Wilberg JMM, et al. Journal of Manipulative and Physiologic Therapeutics. October 1999; Vol.22, No.8, pp.517-522. For information about your injury call to make an appointment.	2	40	1	0	0	0	0.335591	1	6,371
Explore health content from A to Z. I need information about... An arrhythmia is an abnormal heart rhythm. Some arrhythmias can cause problems with contractions of the heart chambers by: Not allowing the ventricles (lower chambers) to fill with an adequate amount of blood because an abnormal electrical signal is causing the heart to pump too fast or too slow. Not allowing a sufficient amount of blood to be pumped out to the body because an abnormal electrical signal is causing the heart to pump too slowly or too irregularly. Not allowing the top chambers to work properly. In any of these situations, the body's vital organs may not receive enough blood to meet their needs. The effects on the body are often the same, however, whether the heartbeat is too fast, too slow, or too irregular. Some symptoms of arrhythmias include, but are not limited to: Palpitations (a sensation of fluttering or irregularity of the heartbeat) Low blood pressure Collapse and cardiac arrest Difficulty feeding (in babies) The symptoms of arrhythmias may resemble other conditions. Consult your doctor for a diagnosis. To better understand arrhythmias, is it helpful to understand the heart's electrical conduction system. The heart is, in the simplest terms, a pump made up of muscle tissue. The heart's pumping action is regulated by an electrical conduction system that coordinates the contraction of the various chambers of the heart. An electrical stimulus is generated by the sinus node (also called the sinoatrial node, or SA node), consisting of a small mass of specialized tissue located in the right atrium (right upper chamber) of the heart. The sinus node generates a regular electrical stimulus, which for adults, is usually 60 to 100 times per minute under normal conditions. This electrical stimulus travels down through the conduction pathways (similar to the way electricity flows through power lines from the power plant to your house) and causes the heart's lower chambers to contract and pump out blood. The right and left atria (the two upper chambers of the heart) are stimulated first and contract a short period of time before the right and left ventricles (the two lower chambers of the heart). The electrical impulse travels from the sinus node to the atrioventricular node (also called AV node), where impulses are slowed down for a very short period, then allowed to continue down the conduction pathway via an electrical channel called the bundle of His into the ventricles. The bundle of His divides into right and left pathways to provide electrical stimulation to the right and left ventricles. Each contraction of the ventricles represents one heartbeat. Each day the heart beats about 100,000 times, on average. Any abnormality in the heart's electrical conduction system can make the heartbeat too fast, too slow, or at an uneven rate, thus, causing an arrhythmia. The electrical activity of the heart is measured by an electrocardiogram (ECG or EKG). By placing electrodes at specific locations on the body (chest, arms, and legs), a graphic representation, or tracing, of the electrical activity can be obtained. Changes in an ECG from the normal tracing can indicate arrhythmias, as well as other heart-related conditions. Almost everyone knows what a basic ECG tracing looks like. But what does it mean? The first little upward notch of the ECG tracing is called the "P wave." The P wave indicates that the atria (the two upper chambers of the heart) are electrically stimulated. This causes them to contract and pump blood to the ventricles. The delay in the conduction of the electrical signal from the atria to the ventricles from the beginning of the P wave to the R (or Q) wave is known as the PR interval. The next part of the tracing is a short downward section connected to a tall upward section. This part is called the "QRS complex." This part indicates that the ventricles (the two lower chambers of the heart) are electrically stimulated (undergo depolarization) to pump out blood to the body via the aorta or to the lungs via the pulmonary artery. The next short flat segment is called the "ST segment." The ST segment is a time when the ventricles are activated and the electrical signal for ventricular contraction is completed. The next upward curve is called the "T wave." The T wave is the electrical recovery period of the ventricles (ventricular repolarization). After the ventricles repolarize, they can then depolarize again. When your doctor studies your ECG, he or she looks at the size, length, and appearance of each part of the ECG. Variations in size and length of the different parts of the tracing may be significant. The tracing for each lead of a 12-lead ECG will look different, but will have the same basic components as described above. Each lead of the 12-lead is "looking" at a specific part of the heart, so variations in a lead may indicate a problem with the part of the heart associated with the lead. An arrhythmia can occur in the sinus node, the atria, or the atrioventricular node. These are supraventricular arrhythmias. A ventricular arrhythmia is caused by an abnormal electrical focus within the ventricles, resulting in abnormal conduction of electrical signals within the ventricles. Arrhythmias can also be classified as slow (bradyarrhythmia) or fast (tachyarrhythmia). "Brady-" means slow, while "tachy-" means fast. Listed below are some of the more common arrhythmias: Sinus arrhythmia. A common condition in which the heart rate varies with breathing. Sinus arrhythmia is commonly found in children; adults may often have it as well. This is a benign (not dangerous) condition. Premature ventricular contractions (PVCs). A condition in which an electrical signal originates in the ventricles and causes the ventricles to contract before receiving the electrical signal from the atria. PVCs are common and typically do not cause symptoms or problems. However, if the frequency of the PVCs increases significantly, symptoms such as weakness, fatigue, dizziness, fainting, or palpitations may be experienced. Heart failure may develop. Sinus tachycardia. A condition in which the heart rate is faster than normal because the sinus node is sending out electrical impulses at a rate faster than usual. Most commonly, sinus tachycardia occurs as a normal response of the heart to exercise when the heart rate increases to cope with increased energy requirements. Sinus tachycardia can be completely appropriate and normal, such as when a person is exercising vigorously. Sinus tachycardia is often temporary, also occurring when the body is under stress from strong emotions, infection, fever, hyperthyroidism, or dehydration, to name a few causes. It may cause symptoms, such as weakness, fatigue, dizziness, or palpitations, if the heart rate becomes too fast to pump an adequate supply of blood to the body. Once the stress is removed, the heart rate will return to its usual rate. Ventricular tachycardia (VT). A potentially life-threatening condition in which an electrical signal is sent from the ventricles at a very fast, but often regular rate. If the heart rate is sustained at a high rate for more than 30 seconds, symptoms, such as weakness, fatigue, dizziness, fainting, or palpitations, may be experienced. Cardiac arrest may occur. A person in VT may require an electric shock or medications to convert the rhythm back to normal sinus rhythm. Sick sinus syndrome. A condition in which the sinus node sends out electrical signals too slowly. There may be alternation between too-fast and too-slow rates (tachy brady syndrome). This condition may cause symptoms if the rate becomes too slow for the body to tolerate. Ventricular fibrillation (VF). A condition in which many electrical signals are sent from the ventricles at a very fast and erratic rate. As a result, the ventricles are unable to fill with blood and pump. This rhythm is life-threatening because there is no pulse and complete loss of consciousness. A person in VF requires prompt defibrillation to restore the normal rhythm and function of the heart. It will result in sudden cardiac death if not treated within seconds. Premature supraventricular contractions or premature atrial contractions (PAC). A condition in which an atrial pacemaker site above the ventricles sends out an electrical signal early. The ventricles are usually able to respond to this signal, but the result is an irregular heart rhythm, which is typically benign. PACs are common and may occur as the result of stimulants such as coffee, tea, alcohol, cigarettes, or medications. Supraventricular tachycardia (SVT). A condition in which the heart rate speeds up due to abnormal tissue above the ventricles. There are several different forms of SVT arrhythmias. A couple of the more common examples include arrhythmias caused by an abnormal electrical connection between the top and bottom chambers of the heart, such as atrioventricular node reentry tachycardia also referred to as paroxysmal SVT, or atrioventricular reentry tachycardia due to an extra conduction pathway between the atria and the ventricles. If that pathway conducts signals from the atria to the ventricles, it is known as Wolff-Parkinson-White Syndrome. Another common SVT form can be caused by a site in the atria that fires rapidly called atrial tachycardia. SVT usually begins and ends rapidly, occurring in repeated periods. These arrhythmias can cause symptoms, such as weakness, fatigue, dizziness, fainting, or palpitations if the heart rate becomes too fast. They can cause shortness of breath or chest discomfort. Atrial flutter. A condition in which the electrical signals come from the atria at a fast but regular rate, often causing the ventricles to contract faster and increase the heart rate. When the signals from the atria are coming at a faster rate than the ventricles can respond to, the ECG pattern typically (but not always) develops a signature "sawtooth" pattern, showing two or more flutter waves between each QRS complex. The number of waves between each QRS complex is expressed as a ratio, for example, a two-to-one atrial flutter means that two waves are occurring between each QRS. Atrial fibrillation. A condition in which the electrical signals come from the atria at a very fast and erratic rate. The ventricles contract in an irregular manner because of the erratic signals coming from the atria A condition in which the electrical signals come from the atria at a very fast and erratic rate. The ventricles contract in an irregular manner because of the erratic signals coming from the atria that activate the AV node. The symptoms of various arrhythmias may resemble other medical conditions. Consult your doctor for a diagnosis. There are several different types of procedures that may be used to diagnose arrhythmias. Some of these procedures include the following: Electrocardiogram (ECG or EKG). An electrocardiogram is a measurement of the electrical activity of the heart. By placing electrodes at specific locations on the body (chest, arms, and legs), a graphic representation, or tracing, of the electrical activity can be obtained as the electrical activity is received and interpreted by an ECG machine. An ECG can indicate the presence of arrhythmias, damage to the heart caused by ischemia (lack of oxygen to the heart muscle) or myocardial infarction (MI, or heart attack), a problem with one or more of the heart valves, or other types of heart conditions. There are several variations of the ECG test: Resting ECG. For this procedure, the clothing on the upper body is removed and small sticky patches called electrodes are attached to the chest, arms, and legs. These electrodes are connected to the ECG machine by wires. The ECG machine is then started and records the heart's electrical activity for a minute or so. The patient is lying down during this ECG. Exercise ECG, or stress test. The patient is attached to the ECG machine as described above. However, rather than lying down, the patient exercises by walking on a treadmill or pedaling a stationary bicycle while the ECG is recorded. This test is done to assess changes in the ECG during stress, such as exercise. Signal-averaged ECG. This procedure is done in the same manner as a resting ECG, except that the heart's electrical activity is recorded over a longer period of time, usually 15 to 20 minutes. Signal-averaged ECGs are done when arrhythmia is suspected but not seen on a resting ECG. The signal-averaged ECG has increased sensitivity to abnormal ventricular activity called "late potentials." Signal-averaged ECG is used in research and seldom used in clinical practice. Electrophysiologic studies (EPS). A test in which a small, thin tube (catheter) is inserted in a large blood vessel in the leg or arm and advanced to the heart. This gives the doctor the capability of finding the site of the arrhythmia's origin within the heart tissue, thus determining how to best treat it. Sometimes an attempt to treat the arrhythmia may be made by doing an ablation at the time of the study. Holter monitor. A continuous ECG recording done over a period of 24 or more hours. Electrodes are attached to the patient's chest and connected to a small portable ECG recorder by lead wires. The patient goes about his or her usual daily activities (except for activities such as taking a shower, swimming, or any activity causing an excessive amount of sweating that would cause the electrodes to become loose or fall off) during this procedure. Holter monitoring may be done when an arrhythmia is suspected but not seen on a resting ECG, since arrhythmias may be transient in nature and not seen during the shorter recording times of the resting ECG. Event monitor. This is similar to a Holter monitor, but the ECG is recorded only when the patient starts the recording when symptoms are felt. Event monitors are typically worn longer than Holter monitors. The monitor can be removed to allow for showering or bathing. Mobile cardiac monitoring. This is similar to both a Holter and event monitor. The ECG is monitored constantly to allow for detection of arrhythmias, which are recorded and sent to your doctor regardless of whether symptoms are experienced. Recordings can also be initiated by the patient when symptoms are felt. These monitors can be worn up to 30 days. Some arrhythmias may be present but cause few, if any, problems. In this case, the doctor may elect not to treat the arrhythmia. However, when the arrhythmia causes symptoms, there are several different options for treatment. The doctor will choose an arrhythmia treatment based on the type of arrhythmia, the severity of symptoms being experienced, and the presence of other conditions (such as, diabetes, kidney failure, or heart failure) which can affect the course of the treatment. Some treatments for arrhythmias include: Lifestyle modification. Factors, such as stress, caffeine, or alcohol, can cause arrhythmias. The doctor may order the elimination of caffeine, alcohol, or any other substances believed to be causing the problem. If stress is suspected as a cause, the doctor may recommend stress-reduction measures, such as meditation, stress-management classes, an exercise program, or psychotherapy. Medication. There are various types of medications that may be used to treat arrhythmias. If the doctor chooses to use medication, the decision of which medication to use will be determined by the type of arrhythmia, other conditions which may be present, and other medications already being taken by the patient. Cardioversion. In this procedure, an electrical shock is delivered to the heart through the chest to stop certain very fast arrhythmias such as atrial fibrillation, supraventricular tachycardia, or atrial flutter. The patient is connected to an ECG monitor which is also connected to the defibrillator. The electrical shock is delivered at a precise point during the ECG cycle to convert the rhythm to a normal one. Ablation. This is an invasive procedure done in the electrophysiology laboratory, which means that a catheter (a very thin, flexible hollow tube) is inserted into the heart through a vessel in the groin or arm. The procedure is done in a manner similar to the electrophysiology studies (EPS) described above. Once the site of the arrhythmia has been determined by EPS, the catheter is moved to the site. By use of a technique, such as radiofrequency ablation (very high frequency radio waves are applied to the site, heating the tissue until the site is destroyed) or cryoablation (an ultra-cold substance is applied to the site, freezing the tissue and destroying the site), the site of the arrhythmia may be destroyed. Pacemaker. A permanent pacemaker is a small device that is implanted under the skin (most often in the shoulder area just under the collar bone), and sends electrical signals to start or regulate a slow heart beat. A permanent pacemaker may be used to make the heart beat if the heart's natural pacemaker (the SA node) is not functioning properly and has developed an abnormal heart rate or rhythm or if the electrical pathways are blocked. Pacemakers are typically used for slow arrhythmias such as sinus bradycardia, sick sinus syndrome, or heart block. Implantable cardioverter defibrillator. An implantable cardioverter defibrillator (ICD) is a small device, similar to a pacemaker, that is implanted under the skin, often in the shoulder area just under the collarbone. An ICD senses the rate of the heartbeat. When the heart rate exceeds a rate programmed into the device, it delivers an electrical shock to the heart in order to correct the rhythm to a slower more normal heart rhythm. ICDs are combined with a pacemaker to deliver an electrical signal to regulate a heart rate that is too slow. ICDs are used for life-threatening fast arrhythmias such as ventricular tachycardia or ventricular fibrillation. Surgery. Surgical treatment for arrhythmias is usually done only when all other appropriate options have failed. Surgical ablation is a major surgical procedure requiring general anesthesia. The chest is opened, exposing the heart. The site of the arrhythmia is located, the tissue is destroyed or removed in order to eliminate the source of the arrhythmia. Copyright © 2014 Baylor Health Care System All Rights Reserved. \| 3500 Gaston Avenue, Dallas, TX 75246-2017 \| 1.800.4BAYLOR	2	6	1	0	0	0	0.841391	1	4,080
The importance of ICD-10 codes One of the types of codes that appear on healthcare provider accounts is known as ICD-10 codes. These codes are used to inform medical schemes about what conditions their members were treated for so that claims can be settled correctly. ICD-10 stands for International Classification of Diseases and Related Health Problems (10th revision). It is a coding system developed by the World Health Organisation (WHO), that translates the written description of medical and health information into standard codes, e.g. J03.9 is an ICD-10 code for acute tonsillitis (unspecified) and G40.9 denotes epilepsy (unspecified). When you join a medical scheme, you choose and pay for a particular benefit option. This benefit option contains a basket of services that often has limits on the health services that will be paid for. Because ICD-10 codes provide accurate information on the condition you have been diagnosed with, these codes help the medical scheme to determine what benefits you are entitled to and how these benefits could be paid. This becomes very important if you have a PMB condition, as these can only be identified by the correct ICD-10 codes. Therefore, if the incorrect ICD-10 codes are provided, your PMB-related services might be paid from the wrong benefit (such as from your medical savings account), or it might not be paid at all if your day-to-day or hospital benefits limits have been exhausted. ICD-10 codes must also be provided on medicine prescriptions and referral notes to other healthcare providers (e.g. pathologists and radiologists) who are not all able to make a diagnosis. Therefore, they require the diagnosis information from your referring doctor so that their claim to your medical scheme can also be paid out of the correct pool of money. Important note: Medical schemes are obliged by law to treat information about members' conditions with the utmost confidentiality. They are not allowed to disclose even ICD-10 codes to any other party, including employers or family members. Responsibilities regarding PMB's Medical scheme beneficiaries PMBs are very good news for medical scheme beneficiaries and give them considerable rights as far as healthcare is concerned. However, as a consumer you also have certain responsibilities to ensure that PMBs work as well for you as they should. - First and foremost, educate yourself about your medical scheme's rules, the listed medication and treatments (formularies) for your specific condition, as well as who the Designated Service Providers (DSPs) are. - Obtain as much information as possible about your condition and the medication and treatments for it. If there is a generic drug available, do your own research to find out whether there are any differences between it and the branded drug. - Don't bypass the system: if you must use a GP to refer you to a specialist, then do so. Make use of your medical scheme's DSPs as far as possible. Stick with your scheme's listed drug for your medication unless it is proven to be ineffective. - Be a good consumer: ask questions and follow the complaints process if you are not treated fairly. - Make sure your doctor submits a complete account to the medical scheme. It is especially important that the correct ICD-10 code is reflected. - Follow up and check that your account is submitted within four months and paid within 30 days after the claim was received (accounts older than four months are not paid by medical schemes). Among other objectives, PMBs want to achieve appropriate healthcare, resulting in lower costs associated with complications and hospitalisation. When beneficiaries are properly taken care of and their illnesses managed, the need for expensive hospitalisation decreases. Medical schemes have a critical role to play in making PMBs work. - Schemes have to educate their beneficiaries about PMBs and the benefits that are included in them. - Schemes must inform their beneficiaries of their DSPs and keep them updated should any changes occur. - Schemes should empower their beneficiaries with information on matters such as the intricacies of rules and the formularies for specific conditions. - Medical schemes have to guarantee and ensure reasonable access and availability of DSPs. - The public sector cannot be designated as a DSP without the medical scheme ensuring that the necessary service will be available. Doctors do not usually have a direct contractual relationship with medical schemes. They merely submit their accounts and if the medical scheme does not pay, for whatever reason, the doctor turns to the beneficiary for the amount due. This does not mean that PMBs are not important to healthcare providers nor that they don't have a role to play in its successful functioning. - Doctors should familiarise themselves with ICD-10 codes and how they correspond with PMB codes. If you use the correct ICD-10 code your account will definitely be paid as PMBs enjoy guaranteed medical aid cover. - Consider on which option your patients are and what can realistically be covered before recommending a drug or treatment. - Alert patients to the fact that their condition is a PMB and encourage them to engage their medical scheme on the matter. - Keep proper clinical records of patients so that when a formulary drug or protocol is not effective, or causes adverse side-effects, you can justify your alternative recommendation. - Do not abuse PMBs. The result will be an unsustainable private healthcare system with unaffordable contribution increases. Abuse could compel government to consider alternative payment options in the private healthcare sector. - Allow your practice to be listed as a DSP. - The "payment in full" concept is there to ensure accessibility of healthcare services for medical scheme beneficiaries if the DSP is not available; it is not a reimbursement model. When do co-payments apply to PMBs? Co-payments can only be levied when members voluntarily choose not to go to a DSP for a specific service, and/or when beneficiaries voluntarily decide not to use protocol or formulary medication or treatments. Co-payments have to be specified in the medical scheme rules and may never be 100% of the cost of the service or medication. Schemes are also not allowed to recover co-payments from beneficiaries' savings accounts. Medical scheme beneficiaries Is my medical scheme obliged by law to provide cover for certain medical conditions? Yes, these are known as Prescribed Minimum Benefits (PMBs). They were introduced into the Medical Schemes Act to ensure that beneficiaries of medical schemes would not run out of benefits for certain conditions and find themselves forced to go to State hospitals for treatment. These PMBs cover a wide range of ±271 conditions, such as meningitis, various cancers, menopausal management, cardiac treatment and many others, including medical emergencies. However, take note that certain limitations could apply, such as the use of a Designated Service Provider and specified treatment standards. PMB diagnosis, treatment and care are not limited to hospitals. Treatment can be received wherever it is most appropriate, including a clinic, outpatient setting or even at home. Always check your benefits with your medical scheme and make sure you have the scheme's rules at your disposal. Is it true that schemes now also have to provide chronic medication? Yes, the list of PMBs includes 26 common chronic diseases in the Chronic Disease List (CDL) and other chronic conditions within the ±271 Diagnosis Treatment Pair (DTP) section. Medical schemes have to provide cover for the diagnosis, treatment and care of these diseases. However, you should remember that a medical scheme does not have to pay for diagnostic tests that establish that you are not suffering from a PMB condition. The treatment algorithms (guidelines for appropriate treatment) for each of the CDL chronic conditions have been published in the Government Gazette while the chronic diseases in the DTP section are guided by the public sector protocols. This assures you of good quality treatment and reassures your medical scheme that it will not have to pay for unnecessary treatment. Your doctor should know and understand most of the guidelines so that he or she can help you get the treatment you need for any of these conditions without incurring costs that your scheme does not cover. Why are some chronic illnesses covered and some not? The diseases that have been chosen are the most common, they are life-threatening, and are those for which cost-effective treatment would sustain and improve the quality of the member's life. Does my scheme need to do anything to ensure that the Designated Service Provider can treat me? The Council for Medical Schemes has been advising medical schemes to enter into contracts with any DSP they choose, especially State hospitals, to ensure that these providers can supply the necessary services. Many State hospitals have set up separate wards to serve beneficiaries whose treatment and hospital stay is paid for by their medical scheme and to whom the hospital can then afford to provide better service. Other schemes have made arrangements with private hospital and certain retail pharmacies to treat their beneficiaries. Can I be refused cover for the chronic conditions if I do not get authorisation or have certain tests? Yes, medical schemes can make a benefit conditional on you obtaining pre-authorisation or joining a benefit management programme. These programmes are aimed at educating members about the nature of their disease and equipping them to manage it in a way that keeps them as healthy as possible. For example, many schemes offer treatment through groups that manage diseases such as diabetes, and are equipped to give the medication and monitor that disease. Can my scheme insist that it will only fund treatment that follows the appropriate protocol? Yes. The minimum medicines for treatment of all PMB conditions have been published in the Government Gazette, and are known as treatment algorithms (benchmarks for treatment). Your scheme may decide for which medicines it will pay for each chronic condition, but the treatment may not be below the standards published in the treatment protocols. If your scheme's cover conforms to that standard and you and your doctor decide that you should rather use different medication, then you may have to pay a co-payment towards the cost of that medicine. Your medical scheme must, however, pay for the treatment if your doctor can prove that the standard medication is ineffective or detrimental to your condition. Your medical scheme may develop protocols to manage the use of benefits. Such protocols would specify, for example, types of tests, investigations and number of consultations. Members who might need more frequent or extra services than provided for in the protocols, can appeal to their scheme for these to be covered. The scheme's appeal process might include a motivation from the treating doctor that explains the clinical reasons for the additional services Can my scheme refuse to cover my medication if I need, or want, a brand other than that which the scheme says it will pay for? Yes, the medical scheme may refuse to cover a part of the expenses. Your scheme may draw up what is known as a formulary – a list of safe and effective medicines that can be prescribed to treat certain conditions. The scheme may state in its rules that it will only cover your medication in full if your doctor prescribes a drug on that formulary. Generally speaking, schemes expect their members to stick to the formulary medication. Often the medicines on the list will be generics – copies of the original brandname drug – that are less expensive but equally effective. If you want to use a brandname medicine that is not on the list, your medical scheme may foot only part of the bill and you will have to pay either the difference between the price of the medication you use and the one on the formulary, or a percentage co-payment as registered in the scheme rules. If you suffer from specific side-effects from drugs on the formulary, or if substituting a drug on the formulary with one you are currently taking affects your health detrimentally, you can put your case to your medical scheme and ask the scheme to pay for your medicine. You can also appeal to the scheme if the formulary drug is ineffective and does not have the desired effect. If your treating doctor can provide the necessary proof and the scheme agrees that you suffer from side-effects, or that the drug is ineffective, then the scheme must give you an alternative and pay for it in full. Can my scheme make me pay for a PMB from my savings account? No, the regulations state that schemes cannot use your medical savings account to pay for PMBs. Can my scheme make me pay a co-payment or levy on a PMB? No, your scheme cannot charge you a co-payment or levy on a PMB if you follow the scheme formulary and protocol. However, if your scheme appoints a Designated Service Provider (DSP) and you voluntarily use a different provider, your scheme may charge you the difference between the actual cost and what it would have paid if you had used the DSP or the percentage co-payment as registered in the scheme rules. Can schemes still set a chronic medicine limit? Yes, your scheme can set a limit for your chronic medicine benefit. Any chronic medication you claim for will then reduce that limit, regardless of whether or not it is one of the PMB chronic conditions. However, if you exhaust your chronic medicine limit, your scheme will have to continue paying for any chronic medication you obtain from its DSP for a PMB condition. Can medical schemes prescribe protocols and formularies? Schemes can most certainly prescribe treatment protocols in terms of PMBs to improve their risk management. However, should medical schemes make use of formularies, these must be developed on the basis of evidence-based medicine, taking cost-effectiveness and affordability into account while also being on par with the gazetted algorithms for chronic diseases and the public sector protocols for the Diagnosis Treatment Pairs. Is there a process to follow when the formulary is not effective for a specific patient? An appeals process is in place for a medical scheme member to request his or her scheme to carry the costs for treatment outside the scheme's formulary. It is very important that complete medical records are submitted in support of the request. As the treating doctor, it is your responsibility to record the patient's reaction to the formulary treatment, including all efforts that were made to determine correct dosages and/or other possible contributing factors. If the PMB codes do not always correspond with the ICD-10 codes, what do I do to ensure a correct account? The Council for Medical Schemes has compiled a guideline on how to reconcile the two sets of codes. However, whenever there are differences between the ICD-10 codes and PMB codes, the latter takes precedence. This guideline is available on the CMS website www.medicalschemes.com under the Regulatory Info menu as "Prescribed minimum benefit ICD-10 coding".	4	2	0	0	0	2	0.860412	2	3,059
Single Payer 101 Source: American Medical Student Association (AMSA) Single payer refers to a way of financing health care, which includes both the collection of money for health care and reimbursement of providers for health care costs. In a single payer system, both the collection of funds and the reimbursement are the responsibility of one entity: the government. The government collects funds from individuals and businesses, mainly in the form of taxes, and the government reimburses providers for health care services delivered to individuals enrolled in the public health insurance program. In the United States, there are multiple payers, not a single payer. The collection of money for health care is a joint responsibility of the private insurance industry, which collects premiums and other payments from individuals and businesses, and the government, which collects taxes from individuals and businesses. Similarly, reimbursement responsibilities fall on both the private insurance industry, which reimburses providers for health care services delivered to privately insured individuals, and the government, which reimburses providers for health care services delivered to publicly insured individuals (e.g. people enrolled in Medicare, Medicaid, S-CHIP, or the VA). Denmark, Sweden, and Canada are example of countries with single payer financing of health care. There is also a single payer system in America: the Medicare program, which is the health insurance program for almost every American aged 65 and over. A provider taking care of a Medicare patient has only one entity to bill: the government. In contrast, a provider has multiple entities to bill when dealing with privately insured individuals due to the large number of private insurance companies in America. Importantly, the term “single payer” is different from “socialized medicine” and “universal health care.” Socialized medicine refers to a system like the National Health Service of the U.K., in which the mechanisms of delivery of health care are owned by the government. That is, the government owns the health care facilities and physicians work for the government. In contrast, the mechanisms of delivery of health care in a single payer system are not necessarily owned by the government. Physicians can be either in private practice or public practice, and hospitals can be both publicly or privately owned. In Canada, for example, physicians are predominantly in private practice, while hospitals are both public and private. As another example, American physicians and hospitals that take care of Medicare patients are usually private. Single payer does not specify a health care delivery mechanism; it specifies a health care financing mechanism. The term “universal health care”, in a general sense, refers to providing every citizen of a country with health insurance. Although universal health care connotes a national public insurance program to some people, there are in reality a variety of ways of achieving universal health care, some of which are predominantly public, and others of which use a mixture of public and private elements. Single payer is one way of achieving universal health care, but other ways include the multi-payer systems of Germany and Japan. FEATURES OF SINGLE PAYER SYSTEMS Single payer systems are heterogeneous; Canada’s system is different from Sweden’s system, which is different from U.S. Medicare, and so on. The well-known Proposal of the Physicians’ Working Group for Single Payer National Health Insurance illustrates one way single payer might look in the United States. The following discussion is based on the details of this proposal.1 Eligibility and Benefits: Every resident of the United States would be enrolled in a public insurance system (the National Health Insurance or “NHI” program). Coverage would include all necessary medical care, including mental health, long-term illness, dental services, and prescription drugs. Coverage decisions would be determined by a national board of experts and community representatives; unnecessary or ineffective interventions would not be covered. Patients would not be billed for medical care covered under the NHI program; rather, all costs for covered services would be paid by the NHI program. Private insurance that covers services covered by the NHI program would be forbidden, although private insurance would be available to insure patients for services not covered under the NHI program. The program would be funded by combining current sources of government health spending (Medicare, Medicaid, etc.) into a single fund with modest new taxes, such as a small payroll tax or earmarked income taxes. While taxes will increase for individual citizens, the increase will be offset by reductions in premiums and out-of-pocket spending. Employees may also receive higher wages from employers, who will no longer have to pay as much for health benefits as part of employee compensation (i.e. instead of paying employees in health benefits, employers will pay higher wages). Hospitals would receive a global budget from the NHI program, which means that they would receive a lump sum to cover all operating expenses every month. Hospitals would need to find a way to stay within their global budget while still providing all necessary medical care. The global budget for the hospital would not cover “capital expenditures” (e.g. facility expansions, purchasing new equipment). Such expenditures would be funded by the NHI program separately from the global budget. Approval for capital expenditures would be based on community needs to prevent over-concentration of technology and facilities in one area. Physicians would remain in private practice or continue to work for private hospitals. In terms of reimbursement, physicians could choose one of three ways of being reimbursed: - Fee-for-service: A national fee schedule will be negotiated each year between the NHI program and provider organizations (e.g. medical associations). - Salary at health care facility: Physicians who work for hospitals and other health care facilities would receive an annual salary. - Salary within a capitated group: A group practice or nonprofit HMO that employs physicians would receive payments from the NHI to pay their physicians. These payments would be capitated – that is, a payment would be made every month for each patient enrolled with a physician to cover the cost of taking care of patients. Medications and supplies: An expert panel would create and maintain a national formulary of prescription drugs covered under the NHI program. Prices for drugs and supplies would be negotiated with the NHI program, which would get a good price from manufacturers due to its bulk purchasing power. THE ARGUMENT FOR SINGLE PAYER The argument for universal health care is both similar to and different from the argument for single payer as the specific mechanism for achieving universal health care. Both arguments include the moral travesty of allowing millions to suffer because they lack health insurance, the economic losses associated with lower productivity due to uninsurance, and the cultural dissonance created when there is not health care for all in a country that purports to believe in equality and equal opportunity.2 In this primer, the argument for single payer will focus on its advantages over methods of achieving universal health care that retain the current system of employer-based insurance and for-profit health insurance companies (employer mandates, individual mandates, expansions of Medicaid, tax credits, etc.). Note that a discussion of single payer vs. multi-payer systems like Germany and Japan, while extremely important, is far beyond the scope of this text. Suffice it to say that many of the advantages ofsingle payer systems are retained by these other systems, and that both single payer and non-single payer universal health care systems have distinct advantages over the other. The argument for single payer can be broken down into two parts: philosophical and economic. The philosophical argument for single payer The U.S. health care system is driven largely by market forces, which are predicated on the profit motive. The theory behind the U.S. system is that private health insurance companies seeking to maximize profit will compete with each other, thus driving down costs. How well does this theory work in practice? From 2000-2004, profits for the top 17 U.S. health insurance companies rose 114%; in contrast, the profits of companies in the S&P 500 (an index of 500 commonly owned stocks) rose 5% during the same period.3 Simultaneously, the number of uninsured individuals grew by six million people, and health insurance premiums rose 60%.3,4 Contrary to popular belief, the newly uninsured were overwhelmingly native citizens, not immigrants.5 This situation – private insurance companies making record profits while health insurance premiums and the number of uninsured skyrocket – suggests that insurance companies have an incentive to price people out of health care to maximize profit. The methods by which private health insurance companies achieve this include denial of insurance to people with pre-existing conditions, heavy utilization review, and “cherry- picking” (selectively insuring the healthy and charging higher premiums for the less healthy).2 Whether this is an acceptable situation depends foremost on how valuable society believes it is to have equitable, universal health care access. The free market in health care may deliver a good health insurance product to those who can afford it, but it is not designed to distribute health insurance equally or universally. Private health insurance companies seeking to maximize profit have no incentive to insure everyone, as this would require them to insure patients with high health care costs. If society believes that equality and universality are important features of a health care system, then the current system is necessarily unacceptable. A single payer system would be a far better alternative. The economic argument for single payer The economic argument for single payer is twofold. First, single payer will save money by reducing administrative costs. Second, and more importantly, single payer greatly facilitates cost control because of its centralized administration. The complexity of the American health care system has been the subject of much criticism. As the prominent Brookings Institute economist Henry Aaron wrote, “Like many other observers, I look at the U.S. health care system and see an administrative monstrosity, a truly bizarre mélange of thousands of payers with payment systems that differ for no socially beneficial reason, as well as staggeringly complex public systems with mind-boggling administered prices and other rules expressing distinctions that can only be regarded as weird.”6 Although administrative costs are commonly discussed, there is much confusion as to exactly what they are. The following figure illustrates the nature of some of the functions that induce administrative costs in the U.S. health care system.7 A 2003 New England Journal of Medicine study calculated the administrative costs involved with insurance overhead, employers’ costs to manage health care benefits, hospital administration (e.g. billing), administrative costs of practitioners (e.g. billing), and administrative costs of long-term care facilities. The study estimated that in 1999, as much as $294.3 billion was used for administrative costs, representing 31.0% of health care expenditures in America. In contrast, in Canada’s single payer system, administrative costs represented 16.7% of health care expenditures.8 A few caveats must be applied here: - The authors themselves acknowledge the imprecision of their estimate and the methodological problems involved with studying administrative costs.8 In addition, one study argued that the $294.3 billion amount is an overestimate of at least $50 billion based on methodological issues.6 The actual number of $294.3 billion should not be taken too literally; the more important point is that the administrative costs in America are very high. - Administrative costs are not bad in and of themselves. Some administrative costs, such as quality improvement or utilization review, may improve quality. Others, such as marketing, advertising, or complex billing due to the plethora of private payers in America, are much more questionable in their usefulness.8 The goal is to reduce administrative costs that are wasteful, not to reduce administrative costs in general. - Comparisons of administrative costs are somewhat difficult to interpret, because different health care systems perform different functions. For instance, Canada’s health care system does not cover outpatient prescription drugs for the most part, while the opposite is true for most American private insurers, Medicaid, the VA, and, as of 2006, Medicare. Such differences are the basis for the common argument from single payer opponents that comparing the administrative costs of the U.S. and Canada is like “comparing apples and oranges.” Although no one claims that the cost of administering a drug plan accounts for more than a small percentage of the difference in administrative costs between American and Canada, it is worth remembering that a simple comparison of administrative costs in two countries is most useful when the specific functions each country’s system performs are identical. - Finally, it should be kept in mind that if the United States adopts a single payer system, the administrative functions the system performs will clearly be different from those of Canada’s.6 No two health care systems are identical. Even with all these caveats in mind, there is little doubt that the administrative costs in America are higher than that in Canada. More importantly, much evidence also suggests that a large portion of administrative costs in the U.S. go to functions that likely do not improve patient care. In support of this notion, a 2005 study showed that in California, private insurers devote 20-22% of their spending to “billing and insurance-related functions” (BIR). While the definition and measurement of BIR is potentially controversial, one conclusion that can be comfortably drawn from the study is that physicians, hospitals, and insurers devote a large amount of money to handling claims and hiring administrative staff to deal with billing.9 These costs, along with costs like marketing and advertising, are among the administrative costs that would be saved by switching to a single-payer system. The specific amount saved would vary according to the design and functions of the new system. Cost control mechanisms To slow the rate of health care expenditure growth, a health care system needs to be able to address the major drivers of health care inflation. In general, administrative costs are not thought to be a major cause of health care inflation.10-12 While these costs represent a large expenditure, reducing administrative costs in a single payer system without instituting other cost control mechanisms would do little to slow the growth of health care costs overall. The strongest economic argument for single payer is that it can control costs in a coordinated fashion because of the centralized nature of its administration. In contrast, because of the non-centralized administration of the U.S. health care system, effective cost controls are difficult to institute. For example, Medicare has been more successful at controlling costs than private insurers in recent years, but these cost controls have had little effect on overall health care costs because private insurers have not instituted the same cost controls as Medicare10-12. In essence, when a health care system has multiple payers who all play by different rules, it is extraordinarily difficult to institute systemic cost controls. When a health care system has a single payer and only one set of rules, cost controls can apply to the entire system. To illustrate this point, consider one of the major drivers of health care inflation: the diffusion of new medical technology.11 Overall, technological innovation has improved health care outcomes for patients, but it has done so at the cost of rapidly increasing health expenditures. Furthermore, not every technological innovation is cost-effective, nor is every technological innovation necessarily an improvement over previous technologies.11 In many other industrialized countries, including countries with single payer systems, there are nationally coordinated attempts to assess the cost-effectiveness of health technologies; the results of these evidence-based assessments are made into national policy. The same cannot be said of the United States. While there are various attempts at evidence-based assessment of health technology in America, the results of these assessments often do not substantially affect the practice of medicine. One reason is that specialists and manufacturers of technology have a disproportionate impact on whether a health insurance company covers new technologies, potentially blunting the effects of any evidence-based reports.11 A more important reason is that in the non-centralized U.S. health care system, the effect of any report will necessarily be limited by how much a given payer decides to use the findings to make decisions about what services to cover.11 For example, even if Medicare decides not to cover a technology deemed ineffective by its internal health technology assessment studies, the government has little power to influence whether private insurance companies cover that particular technology. In a single payer system, the government could theoretically use evidence-based assessment of technology to determine what is covered throughout the system, thus minimizing the use of ineffective technologies. As another example of the power of single payer systems to control costs because of its centralized administration, consider cost controls such as global budgeting for hospitals and supply limitations (e.g. preventing the purchase of too many MRIs in an area that is already oversaturated with MRIs). These measures are known to be some of the strongest cost controls available to policy makers. Indeed, other countries have been able to successfully institute such controls, slow down the rate of health care expenditure inflation, and still provide high-quality coverage to its citizens.12 However, the U.S. experience with such controls is limited. This can partly be attributed to politics, but it can also be partly attributed to the impracticality of attempting to institute such controls when there is not one centralized entity overseeing the system. Other cost controls There are a variety of other economic advantages of single payer systems in terms of cost control. First, single payer systems can get better prices for goods and services because of their bulk purchasing power. One study compared the price of a defined group of medications in different countries. The price of these medications in Canada, which uses its purchasing power to negotiate with drug companies, was 60% of the cost of the medications in America.12 Second, because billing is done by one entity, single payer systems facilitate the collection of massive databases that can be used to study and potentially improve practice patterns. The databases can also be used to screen for fraudulent billing by providers, as has been done in Taiwan’s new single-payer system.14 A caveat about cost controls in single payer systems It is important to note that all cost control mechanisms have potential disadvantages and that none of these cost controls discussed above are intrinsic to single payer systems. That is, any given single payer system would not necessarily have global budgeting for hospitals, limitations on technology, etc. The important point is that a single payer system enables the option of instituting these cost controls, whereas that option is not available to policymakers in the current fragmented U.S. health care system. Another important point is that decisions about cost controls in a single payer system will involve a good deal of public debate, as they do in Canada. For example, the public will have influence over what is and what is not covered in the single payer system; if there is a public outcry for technology even though it means paying more for health care, then the system will adapt to these demands. In the current system, as discussed above, coverage decisions by private insurance companies are dominated by special interests, and consumers play a very minor role.11 A system in which decision makers are directly accountable to the public is more likely to be more responsive to public opinion than the current system, in which decision makers (i.e. private insurance company executives) are not directly accountable to the public. In summary, perhaps the strongest economic argument for single payer is that it gives policymakers the option of controlling costs. Whether they elect to use this option will be influenced by a democratic process that incorporates the needs of the American public. ADVANTAGES OF SINGLE PAYER TO VARIOUS GROUPS OF PEOPLE The benefits of single payer are numerous, but they do not accrue to all sectors of society. Clearly, private health insurance companies do not stand to gain from a single payer system, as their role would be dramatically minimized. Furthermore, the pharmaceutical industry does not stand to gain from a single payer system because of the potential for price controls and bulk purchasing. For most Americans, though, single payer would represent a clear improvement over the current system: Advantages to patients - Improved health. The most prominent benefit of single payer is that patients will be able to access health care with minimal financial barriers. This improved access will increase health by increasing preventive/primary care and allowing patients to afford their treatment regimens. - Free choice of provider. Patients will have free choice to choose their doctor. In the current system, not every provider accepts every form of health insurance, and the existence of managed care preferred provider networks is an impediment to free choice of providers. - Portability of coverage. In the current system, insurance status is linked to employment. In a single payer system, a person can go from job to job without experiencing interruptions in health insurance coverage. - De-linking insurance status with employment will also increase the number of small businesses, as there are many people who refrain from starting their own businesses because they are afraid to lose their health insurance (the “job lock” phenomenon).15 Advantages to physicians - Restoration of clinical autonomy: The United States arguably has some of the most intrusive regulation of physician behavior of any industrialized country.16 This regulation comes mainly through private insurance companies, particularly managed care companies that require pre-approval for interventions and institute heavy utilization reviews. In a single payer system, physicians will be relieved from the burden of these regulations, increasing their clinical autonomy. - Lower malpractice premiums: Currently, a significant portion of malpractice jury awards are devoted to future medical costs for the patient. Under a single payer system, this percentage would decrease, as the government would pay for these future medical costs.8 In addition, a single payer system may be able to decrease medical errors and therefore the number of malpractice suits by increasing continuity of care. That is, patients would not shuttle from doctor to doctor because they change insurance companies or their insurance company alters its preferred provider network. - Improved patient care. Physicians will be able to make clinical decisions based on best practices, as the influence of a patient’s financial circumstances will be decreased. Physicians will also enjoy increased compliance by patients, who will be able to afford the medications and interventions prescribed to them. - Simplified billing. Since physicians will have only one entity to bill, billing will be greatly simplified. Physicians will save money on overhead because they will not have to hire to hire as many administrative staff to deal with billing. Advantages to businesses - Decreased health care costs. In 2005, the average employer-based health insurance premium for a family of four was $10,880, while the premium was $4,024 for an individual.17 Under a single payer system, businesses will no longer be required to cover the vast majority of health insurance premiums for their employees. Depending on the specific proposal, businesses might be required to fund the new health care system through a payroll tax, but for most businesses, such a payroll tax is likely to cost less than providing health insurance for employees. - Equal playing field. The businesses that stand to lose money in a single payer system are those that do not currently provide health insurance. Workers in such businesses either enroll in Medicaid, which is taxpayer-funded, or they become uninsured and receive uncompensated care, which is predominantly financed by taxpayer money. Moreover, businesses that do not provide health insurance gain an advantage over businesses that do provide health insurance. Single payer would eliminate this advantage, thus leveling the playing field for businesses. - Improved global competitiveness. The relief of the health care burden on businesses will help stimulate the economy and improve the global competitiveness of U.S. businesses. Currently, U.S. businesses are a competitive disadvantage to foreign companies, which have lower health care costs and therefore lower prices on their products.18 THE POTENTIAL DISADVANTAGES OF SINGLE PAYER The vitality of any public program lies in its funding levels, and the biggest potential disadvantage to a single payer system is the threat of underfunding. There are several ways in which this might occur: - Underfunding by a hostile government: a government that favors privatization might take measures to undermine the public system. In America, the strength of private special interests makes this possibility especially worrisome. - Mismanagement: an inept or corrupt government could misallocate funds in a single payer system, taking away money from vital services and decreasing quality. - Recession: public systems rely on tax dollars, which decrease during recessions. Another potential disadvantage of single payer relates to one of its strengths: the ability to control costs. As noted above, all cost control mechanisms have downsides, and overly aggressive cost control could result in decreases in quality. For instance, inappropriately strict limits on the diffusion of technology might stifle positive innovation in technology. Along with underfunding, this can be avoided through prudent management of the health care system, but it remains a potential concern. The transition from the current system to a single payer would undoubtedly be very difficult. Thousands of people who work for private insurance companies would need to be shifted to other sectors of the economy. Even though these individuals could be trained to work in the new public system, they would still experience a significant change in their lives. Because of these considerations, most single payer advocates and policy analysts believe that any transition to a single payer system would necessarily be gradual, taking place over the course of many years. Finally, there are some important tradeoffs that Americans will have to make in a single payer system. The first is that technology-hungry Americans will have to accept limits on ineffective, questionable, or medically unnecessary interventions that would not be covered by the single payer system. Such interventions could be likely be covered by supplemental private insurance, as is the case in other countries with single payer. The second major tradeoff is that Americans will have to accept less choice in insurance plans. Some Americans want to choose the health insurance plan that is tailored to their individual needs, but a single payer system would give everyone the same insurance plan. The last major tradeoff is that Americans will have to accept more government control and less private control of the health care system. Neither the government nor the private insurance industry can currently claim great popularity with Americans, and the question is which entity Americans will trust more to manage the health care system. This primer has endeavored to articulate the nature and advantages of a single payer system. Solutions that achieve universal health care through mechanisms that build on the current system of for-profit employer-based insurance, while potentially beneficial, do not achieve the philosophical purity, administrative simplification, or cost control potential that a single payer system achieves. Single payer, however, has significant potential disadvantages that must be addressed. Although many of the disadvantages can be avoided through proper management of the system (e.g. funding the system at a very high level and insuring adequate capacity), others represent true tradeoffs that the American public must debate in its mind. The time for such debates is now. In the current system, insurance companies have a financial incentive to avoid insuring the people who need it the most, which means that more and more Americans suffer every year. It is only a matter of time before some type of reform takes place, and single payer should be a reform option that should be seriously considered. Contact: Written by Kao-Ping Chua Flávio Casoy AMSA Jack Rutledge Fellow 2005-2006 AMSA Jack Rutledge Fellow Updated by Flávio Casoy 1902 Association Drive AMSA Jack Rutledge Fellow 2007-2008 Reston, VA 20191 (703) 620-6600 x256 1. Physicians’ Working Group. “Proposal of the Physicians’ Working Group for Single Payer Health Insurance”. JAMA 290(6):798-805, 2003. 2. American Medical Student Association. “The Case for Universal Health Care”, 2006. 3. Britt, R. “Health Insurers Getting Bigger Cut of Medical Dollars.” Investors’ Business Daily, Oct. 15, 2004. Available at 4. Kaiser Family Foundation. “The Uninsured and Their Access to Health Care.” Fact Sheet #1402-07, November 2005. 5. Holahan, J. and Cook, A. “Are Immigrants Responsible for Most of the Growth in the Uninsured?” Kaiser Commission on Medicaid and the Uninsured, October 2005. 6. Aaron, H. "The Costs of Health Care Administration in the United States and Canada—Questionable Answers to a Questionable Question," New England Journal of Medicine 349(9):801–803, 2003. 7. Thorpe, K. “Inside the Black Box of Administrative Costs.” Health Affairs 11(2):41- 55, 1992. 8. Woolhandler, S., Campbell, T., and Himmelstein, D. “Costs of Health Care Administration in the United States and Canada.” New England Journal of Medicine 349:768-775, 2003. 9. Kahn, J., Kronick R., Kreger, M., and Gans, D. “The Cost of Health Insurance Administration in California: Estimates for Insurers, Physicians, and Hospitals.” Health Affairs 24(6):1629-1639, 2005. 10. Bodenheimer, T. “High and Rising Health Care Costs. Part 1.” Annuals of Internal Medicine, 142: 847-854, 2005. 11. Bodenheimer, T. “High and Rising Health Care Costs. Part 2.” Annuals of Internal Medicine, 142: 932-937, 2005. 12. Bodenheimer, T. “High and Rising Health Care Costs. Part 3.” Annuals of Internal Medicine, 142: 996-1002, 2005. 13. Bodenheimer, T. “High and Rising Health Care Costs. Part 4.” Annuals of Internal Medicine, 143: 26-31, 2005. 14. Lu, R. and Hsiao, B. “Does Universal Health Insurance Make Health Care Unaffordable? Lessons from Taiwan.” Health Affairs 22(3):77-88, 2003. 15. Hopkins, J. “Health Insurance Costs Dog Would-Be Entrepreneurs.” USA Today, August 8, 2005. 16. Oberlander J. and Marmor, T. “The path to universal health care.” In: Borosage R., Hickey, R., editors. The next agenda. Boulder (CO): Westview Press; 2001. p. 93- 125. 17. Kaiser Family Foundation. “Employer Health Benefits 2005 Annual Survey”, 2005. 18. Associated Press. “GM to slash jobs, close more plants.” Available at	2	6	1	0	0	0	0.646588	1	6,435
The diagnosis of Graves’ disease is usually easily made. The combination of eye signs, goiter, and any of the characteristic symptoms and signs of hyperthyroidism forms a picture that can hardly escape recognition (Fig -1). It is only in the atypical cases, or with coexisting disease, or in mild or early disease, that the diagnosis may be in doubt. The symptoms and signs have been described in detail in the section on manifestations of Graves’ disease. For convenience, the classic findings from the history and physical examination are grouped together in Table 1a and 1b.These occur with sufficient regularity that clinical diagnosis can be reasonably accurate. Scoring the presence or absence and severity of particular symptoms and signs can provide a clinical diagnostic index almost as reliable a diagnostic measure as laboratory tests(1). Occasionally diagnosis is not at all obvious.In patients severely ill with other disease, in elderly patients with “apathetic hypothyroidism”, or when the presenting symptom is unusual, such as muscle weakness, or psychosis, the diagnosis depends on clinical alertness and laboratory tests. The diagnosis of Graves’ Disease does not depend on thyrotoxicosis. Ophthalmopathy, or pretibial myxedema are seen without goiter and thyrotoxicosis, or even with spontaneous hypothyroidism. While proper classification can be debated, these patients seem to represent one end of the spectrum of Graves’ Disease. Thus we are usually making two coincident diagnoses:1)- Is the patient hyperthyroid? and 2)- Is the cause of the problem Graves’ disease. \|Table 1a SYMPTOMS\| \|Table 1b PHYSICAL SIGNS\| Hyperpigmentation or vitiligo LABORATORY DIAGNOSIS OF GRAVE’S DISEASE Serum Hormone Measurements TSH and FT4 assay- Once the question of thyrotoxicosis has been raised, laboratory data are required to verify the diagnosis, help estimate the severity of the condition, and assist in planning therapy. A single test such as the TSH or estimate of FT4 (free T4) may be enough, but in view of the sources of error in all determinations, most clinicians prefer to assess two more or less independent measures of thyroid function. For this purpose, an assessment of FT4 and sensitive TSH are suitable. As an initial single test, a sensitive TSH assay may be most cost-effective and specific. TSH should be 0 – .1 µU/ml in significant thyrotoxicosis, although values of .1 – .3 are seen in patients with mild illness, especially with smoldering toxic multinodular goiter in older patients(1.1). TSH can be low in some elderly patients without evidence of thyroid disease. TSH can be normal — or elevated — only if there are spurious test results from antibodies, or the thyrotoxicosis is TSH-driven, as in a pituitary TSH-secreting adenoma or pituitary resistance to thyroid hormone. Measurement of FT4 or FTI(Free thyroxine index)is also usually diagnostic.The degree of elevation of the FT4 above normal provides an estimate of the severity of the disease. During replacement therapy with thyroxine the range of both FTI and FT4 values tend to be about 20% above the normal range, possibly because only T4 , rather than T4 and T3 from the thyroid, is providing the initial supply of hormone. Thus many patients will have an FT4 or FTI above normal when appropriately replaced and while TSH is in the normal range. Except for this, elevations of FT4 not due to thyrotoxicosis are unusual, and causes are given in Table 3. Of course the Total T4 level may normally be as high as 16 or 20 µg/dl in pregnancy, and can be elevated without thyrotoxicosis in patients with familial hyperthyroxinemia due to abnormal albumin, the presence of hereditary excess TBG, the presence of antibodies binding T4 , the thyroid hormone resistance syndrome, and conditions listed in Table 3. The T4 level may be normal in thyrotoxic patients who have depressed serum levels of T4 -binding protein or because of severe illness, even though they are toxic. Thus, thyrotoxicosis may exist when the total T4 level is in the normal range.However measurement of FT4, FT3, or FTI usually obviates this source of error and is the best test. In the presence of typical symptoms, one measurement of suppressed TSH or elevated FT4 is sufficient to make a definite diagnosis, although it does not identify a cause. If the FT4 is normal, repetition is in order to rule out error, along with a second test such as serum FT3. A variety of methods for FT4 determination have become available, including commercial kits. Although these methods are usually reliable, assays using different kits do not always agree among themselves or with the determination of free T4 by dialysis. Usually T4 and T3 levels are both elevated in thyrotoxicosis, as is the FTI (Free Thyroxin Index), or an index constructed using the serum T3 and rT3U levels, and the newer measures of FT3. \|Table 3. Conditions Associated with Transient Elevations of the FT4 or FTI\| \|Estrogen withdrawal\|\|Rapid decrease in TBG level\| \|Amphetamine abuse\|\|Possibly induced TSH secretion(2)\| \|Hyperemesis gravidarum\|\|hCG, can cause thyrotoxicosis\| \|Iodide administration\|\|Thyroid autonomy\| \|Beginning of T4 administration\|\|Delayed T4 metabolism(3)\| \|Severe illness (rarely)\|\|Decreased T4 to T3 conversion (4)\| \|Amiodarone treatment\|\|Decreased T4 to T3 conversion, iodine load\| \|Gallbladder contrast agents\|\|Decreased T4 to T3 conversion, iodine load\| \|Propranolol (large doses)\|\|Inhibition of T4 to T3 conversion\| \|Prednisone (rarely)\|\|Inhibition of T4 to T3 conversion\| \|High altitude exposure\|\|Possibly hypothalamic activation\| \|Selenium deficiency\|\|Decreased T4 to T3 conversion\| T3 and FT3 ASSAY- The serumT3 level determined by RIA is almost always elevated in thyrotoxicosis and is a useful but not commonly needed secondary test. Usually the serum T3 test is interpreted directly without use of a correction for protein binding, since alterations of TBG affect T3 to a lesser extent than T4. Any confusion caused by alterations in binding proteins can be avoided by use of a FT3 assay or T3 index calculated as for the FTI. Generally the FT3 assay is as diagnostically effective as the FT4. In patients with severe illness and thyrotoxicosis, especially those with liver disease or malnutrition or who are taking steroids or propranolol, the serum T3 level may not be elevated, since peripheral deiodination of T4 to T3 is suppressed (“T4 toxicosis”). A normal T3 level has also been observed in thyrotoxicosis combined with diabetic ketoacidosis. Whether or not these patients actually have tissue hypermetabolism at the time their serum T3 is normal is not entirely certain. In these patients the rT3 level may be elevated. If the complicating illness subsides, the normal pattern of elevated T4 , FTI, and T3 levels may return(5,6). Elevated T4 levels with normal serum T3 levels are also found in patients with thyrotoxicosis produced by iodine ingestion(7). Since 1957, when the first patient with T3 thyrotoxicosis was identified, a number of patients have been detected who had clinical thyrotoxicosis, normal serum levels of T4 and TBG, and elevated concentrations of T3 and FT3. Hollander et al found that approximately 4% of patients with thyrotoxicosis in the New York area fit this category. These patients often have mild disease but otherwise have been indistinguishable clinically from others with thyrotoxicosis. Some have had the diffuse thyroid hyperplasia of Graves’ disease, others toxic nodular goiter, and still others thyrotoxicosis with hyperfunctioning adenomas. Interestingly, in Chile, a country with generalized iodine deficiency, 12.5% of thyrotoxic subjects fulfilled the criteria for T3 thyrotoxicosis . Asymptomatic hypertriiodothyronemia is an occasional finding several months before the development of thyrotoxicosis with elevated T4 levels . Since T4 is normally metabolized to T3, and the latter hormone is predominantly the hormone bound to nuclear receptors, it makes sense that elevation of T3 alone can produce thyrotoxicosis. Thyroid Isotope uptake In patients with thyrotoxicosis the RAIU (Radioactive Iodine Uptake) at 24 hours is characteristically above normal. In the United States, which has had an increasing iodine supply in recent years, the upper limit of normal is now about 25% of the administered dose. This value is higher in areas of iodine deficiency and endemic goiter. The uptake value at a shorter time interval, for example 6 hours, is as valid a test and may be more useful in the infrequent cases having such a rapid isotope turnover that “uptake” has fallen to normal by 24 hours. If there is reason to suspect that thyroid isotope turnover is rapid, it is wise to do both a 6- and a 24-hour RAIU determination during the initial laboratory study. As noted below, rapid turnover of 131-I can seriously reduce the effectiveness of 131-I therapy. Similar studies can be done with 123-I and also technetium.Because of convenience, and since serum assays of thyroid hormones and TSH are reliable and readily available, the RAIU is now infrequently determined unless 131-I therapy is planned. A drawback of this approach is that cases of transient thyrotoxicosis (described below) may be missed unless the typical low RAIU is recognized. To avoid errors, we recommend that the RAIU test be done in patients who are believed to be thyrotoxic with suppressed TSH, but who do not have typical symptoms and/or signs. This may include patients with brief symptom duration, small goiter, or lacking eye signs, absent family history, or negative antibody test result. Obviously other causes of a low RAIU test need to be considered and excluded. Tests measurinjg suppressibility of RAIU are of some historical interest(13-15) Isotope scanning of the thyroid has a limited role in the diagnosis of thyrotoxicosis. It is useful in patients in whom the thyroid is difficult to feel or in whom nodules (single or multiple) are present that require evaluation, or rarely to prove the function of ectopic thyroid tissue. Nodules may be incidental, or may be the source of thyrotoxicosis (toxic adenoma), or may contribute to the thyrotoxicosis that also arises from the rest of the gland. Scanning should usually be done with 123-I in this situation, in order to combine it with an RAIU measurement. Thyroid Ultrasound- US exam of the thyroid is sometimes of value in diagnosis. For example, if a possible nodule is detected on physical exam. It also may confirm hypoechogenicity if the diagnosis is actually Hashimoto’s thyroiditis, or intense vascularity of Graves’ disease if a color Doppler flow exam is done. Determination of antibody titers provides supporting evidence for Graves’ disease. More than 95% of patients have positive assays for TPO (microsomal antigen), and about 50% have positive anti-thyroglobulin antibody assays. In thyroiditis the prevalence of positive TG antibody assays is higher. Positive assays prove that autoimmunity is present, but they do not prove thyrotoxicosis. However, patients with causes of thyrotoxicosis other than Graves’ disease usually have negative assays. During therapy with antithyroid drugs the titers characteristically go down, and this change persists during remission. Titers tend to become more elevated after RAI treatment. Antibodies to TSH-Receptor- Thyrotrophin receptor antibody assays (TRAb) have become readily available, and a positive result strongly supports the diagnosis of Graves’ disease(11.1). Determination of TRAb is not required for the diagnosis, but the implied specificity of a positive test provides security in diagnosis, and for this reason the assay is now widely used. The assay is valuable as another supporting fact in establishing the cause of exophthalmos, in the absence of thyrotoxicosis, and high maternal levels predict fetal or neonatal thyrotoxicosis. Measurement of TRAb (TSH-R binding antibodies), any antibody that binds to the TSH-R, is generally available.Assays for Thyroid Stimulating Antibodies (TSAb,TSI) are less available, but are more specific for the diagnosis. Using current tests, both are positive in about 90% of patients with Graves disease who are thyrotoxic. “Second generation” assays becoming available use monoclonal anti-TSH-R antibodies and biosynthetic TSH-R in coated tube assays, are reported to reach 99% specificity and sensitivity(11.11,11.12,16). Although rarely required, serial assays are of interest in following a patient’s course during antithyroid drug therapy, and a decrease predicts probable remission(11.2). Other Assays Rarely Used- General availability of assays that can reliably measure suppressed TSH has made this the gold standard to which other tests must be compared, and has effectively eliminated the need for most previously used ancillary tests. There are only rare causes of confusion in the TSH assay. Severe illness, dopamine and steroids, and hypopituitarism, can cause low TSH, but suppression below 0.1 µ/ml is uncommon and below 0.05 µ/ml is exceptional, except in thyrotoxicosis. Thyrotoxicosis is associated with normal or high TSH in patients with TSH producing pituitary tumors and selective pituitary resistance to thyroid hormone. If TSH, FT4, TRAb, and other test noted above do not establish the diagnosis, it may be wise to do nothing further except to observe the course of events. In patients with significant thyroid hyperfunction, the symptoms and signs will become clearer, and the laboratory measurements will fall into line. Measurement of BMR, T3 suppression of RAIU, TRH testing, and response to KI are of historical interest. DIFFERENTIAL DIAGNOSIS of THYROTOXICOSIS Graves’ disease must be differentiated from other conditions causing thyrotoxicosis. (Table -4). Thyrotoxicosis factitia-Thyrotoxicosis may be caused by taking T4 or its analogs, most commonly due to administration of excessive replacement hormone by the patient’s physician.Hormone may be taken surreptitiously by the patient for weight loss or psychologic reasons. The typical findings are a normal or small thyroid gland, an131-I uptake of zero, a low serum TG, and, of course, a striking lack of response to antithyroid drug therapy. The problem can easily be confused with “painless thyroiditis”, but in thyrotoxicosis factitia, the gland is typically small. Toxic nodular goiter is usually distinguished by careful physical examination and a history of goiter for many years before symptoms of hyperthyroidism developed. The thyrotoxicosis comes on insidiously, and often, in the older people usually afflicted, symptoms may be mild, or suggest another problem such as heart disease. The thyroid scan may be diagnostic, showing areas of increased and decreased isotope uptake. The results of assays for antithyroid antibodies, including TSAb, are usually negative. TMNG is typically produced by activating somatic mutations in TSH-R in one or more nodules, allowing them to enlarge and become functional even in the absence of TSH stimulation. (Interestingly, cats are well known to develop hyperthyroidism, with thyroid autonomy, often due to TSH-R gene mutations as seen in humans.) Hyperfunctioning solitary adenoma is suggested on physical examination by atrophy of the remainder of the thyroid, and is proved by a scintiscan demonstrating preferential radioisotope accumulation in the nodule. This type of adenoma must be differentiated from congenital absence of one of the lobes of the thyroid. Toxic nodules typically present in adults with gradually developing hyperthyroidism and a nodule > 3 cm in size. These nodules are usually caused by activating somatic mutations in the TSH-R, which endows them with mildly increased function, compared to normal tissue, even in the absence of TSH. These nodules are usually, but not always, monoclonal(17). In adults toxic nodules are very rarely malignant. Rarely, functioning thyroid carcinomas produce thyrotoxicosis. The diagnosis is made by the history, absence of the normal thyroid, and usually widespread functioning metastasis in lung or bones. Invasion of the gland by lymphoma has produced thyrotoxicosis . Thyrotoxicosis associated with subacute thyroiditis is usually mild and transient, and the patient lacks the physical findings of long-standing thyrotoxicosis. If thyrotoxicosis is found in conjunction with a painful goiter and low or absent 131-I uptake, this diagnosis is likely. Usually the erythrocyte sedimentation rate (ESR) and CRP are greatly elevated, and the leukocyte count may also be increased. Occasionally the goiter is non-tender. Antibody titers are low or negative. Many patients have the HLA-B35 antigen, indicating a genetic predisposition to the disease. The rare TSH secreting pituitary adenoma will be missed unless one measures the plasma TSH level, or until the enlargement is sufficient to produce deficiencies in other hormones, pressure symptoms, or expansion of the sella turcica(20). These patients have thyrotoxicosis with inappropriately elevated TSH levels and may/or may not secrete more TSH after TRH stimulation. The characteristic finding is a normal or elevated TSH, and an elevated TSH alpha subunit level in blood, measured by special RIA. TRAbs are not present. Exophthalmos, family history, and antibodies of Graves’ disease are absent. Demonstration of a suppressed TSH level excludes these rare cases. The category of patients with thyrotoxicosis and inappropriately elevated TSH levels also includes the very rare persons with excess TRH secretion, or pituitary “T3 resistance” as a part of the Resistance to Thyroid Hormone syndrome caused usually by TH Receptor mutations. TRH hypersecretion, a possible cause of thyrotoxicosis , is marked by an absence of pituitary tumor, elevated TSH levels, and failure to respond to TRH. The syndrome of Pituitary Thyroid Hormone Resistance is usually marked by mild thyrotoxicosis, mildly elevated TSH levels, absence of pituitary tumor, a generous response to TRH, no excess TSH alpha subunit secretion [19,21],and by TSH suppression if large doses of T3 are administered. Final diagnosis depends on laboratory demonstration of a mutation in the TR gene, if possible. Administration of large amounts of iodide in medicines, for roentgenographic examinations, or in foods can occasionally precipitate thyrotoxicosis in patients with multinodular goiter or functioning adenomas. This history is important to consider since the illness may be self-limiting. Induction of thyrotoxicosis has also been observed in apparently normal individuals following prolonged exposure to organic iodide containing compounds such as antiseptic soaps and amiodarone. Amiodarone is of special importance since the clinical problem often is the presentation of thyrotoxicosis in a patient with serious cardiac disease including dysrythmia. Amodarone can induce thyrotoxicosis in patients without known prior thyroid disease, or with multinodular goiter. The illness appears to come in two forms. In one the RAIU may be low or normal. In the second variety , which appears to be more of a thyroiditis-like syndrome, the RAIU is very suppressed, and IL-6 may be elevated. In either case TSH is suppressed, FTI may be normal or elevated, but T3 is elevated if the patient is toxic. Antibodies are usually negative. An increasingly recognized form of thyrotoxicosis is the syndrome described variously as painless thyroiditis, transient thyrotoxicosis, or “hyperthyroiditis“. Its hallmarks are self-limited thyrotoxicosis, small painless goiter, and low or zero RAIU(22,23). The patients usually have no eye signs, a negative family history, and low antibody titers. This condition is due to autoimmune thyroid disease, and is considered a variant of Hashimoto’s Thyroiditis. It occurs sporadically, usually in young adults. It frequently occurs 3 – 12 weeks after delivery, sometimes representing the effects of immunologic rebound from the immunosuppressive effects of pregnancy in patients with Hashimoto’s thyroiditis or prior Graves’ Disease, and is called Post Partum Thyroiditis(12,24,25). The course typically includes development of a painless goiter, mild to moderate thyrotoxicosis, no eye signs, remission of symptoms in 3 -20 weeks, and often a period of hypothyroidism before return to euthyroid function. The cycle may be repeated several times. Histologic examination shows chronic thyroiditis, but it is not typical of Hashimoto’s disease or subacute thyroiditis and may revert to normal after the attack(26). In most patients, the thyrotoxic episode occurs in the absence of circulating TSAb. This finding suggests that the pathogenesis is quite distinct from that in Graves’ disease. The thyrotoxicosis is caused by an inflammation-induced discharge of preformed hormone due to the thyroiditis. The T4/T3 ratio is higher than in typical Graves’ disease,and thyroid iodine stores are depleted. Since the thyrotoxicosis is due to an inflammatory process, therapy with antithyroid drugs or potassium iodide is usually to no avail, and RAI treatment of course cannot be given when RAIU is suppressed. Propranolol is usually helpful for symptoms. Glucocorticoids may be of help if the process — often transient and mild — requires some form of therapy. Propylthiouracil and/or ipodate can be used to decrease T4 to T3 conversion and will ameliorate the illness. Repeated episodes may be handled by surgery or by RAI therapy during a remission. Occasionally painless post-partum thyroiditis is followed by typical Graves’ Disease(27-29). Hyperemisis gravidarum is usually associated with elevated serum T4 , FTI, and variably elevated T3, and suppressed TSH. The abnormalities in thyroid function are caused by high levels of hCG. This molecule, or a closely related form, share enough homology with TSH so that it has about 1/1000 the thyroid stimulating activity of TSH, and can produce thyroid stimulation or thyrotoxicosis(29.4,29.5,30,32). It is typically self limited without specific treatment, disappears with termination of pregnancy, but may occasionally require anti-thyroid treatment temporarily or throughout pregnancy(29.3). Patients with minimal signs and symptoms, small or no goiter, and elevation of FTI up to 50 % above normal probably do not require treatment. Those with goiter, moderate or severe clinical evidence of thyrotoxicosis, highly elevated T4 and T3 and suppressed TSH are best treated with antithyroid drugs. If antibodies are positive or eye signs are present, the picture is usually interpreted as a form of Graves’ disease. Familial severe hyperemesis gravidarum with fetal loss has been reported with an activating germline mutation in the TSH-R, which made it specifically more sensitive to activation by hCG. Hyperthyroidism can be induced by “hyperplacentosis”, which is characterized by increased placental weight and circulating hCG levels higher than those in normal pregnancy(29.6). After hysterotomy, hCG levels declined in the one case reported and hyperthyroidism was corrected. Congenital hyperthyroidism caused by a germ-line activating mutation in the TSH-R has recently been recognized . The mutations are usually single aminoacid transitions in the extracellular loops or transmembrane segments of the receptor trans-membrane domain. The diagnosis may be difficult to recognize in the absence of a family history. However the patients lack eye signs, and have negative assays for antibodies(29.1) (For interest, a similar syndrome occurs in cats(16.1)). Hydatidiform moles, choriocarcinomas, and rarely seminomas secrete vast amounts of hCG. hCG, with an alpha subunit identical to TSH , and beta subunit related to TSH , binds to and activates the thyroid TSH receptor with about 1/1,000th the efficiency of TSH itself (Fig.-3)(31-33). Current evidence indicates that very elevated levels of native hCG or perhaps desialated hCG, cause the thyroid stimulation. Many patients have goiter or elevated thyroid hormone levels or both, but little evidence of thyrotoxicosis, whereas others are clearly thyrotoxic. Diagnosis rests on recognizing the tumor (typically during or after pregnancy) and measurement of hCG. Therapy is directed at the tumor. Hyperthyroidism also is seen as one manifestation of autoimmune thyroid disease induced by interferon-alpha treatment of chronic hepatitis C. It can be self limiting, or severe enough to require cessation of IFN, or in some cases continue on after INF is stopped(33.1). Hyperthyroidism also occurs during immune reconstitution seen after effective anti-viral therapy of patients with HIV(33.2), has occurred during recovery of low lymphocyte levels induced by therapy with CAMPATH in patients with Multiple sclerosis, has occurred after cessation of immune-suppressive treatment in patients with T1DM, and has developed during thyroid invasion by lymphoma(18). \|Table 4. Causes of Thyrotoxicosis\| Course of disease \|Graves’ disease\|\|Familial, prolonged\|\|Goiter\|\|+ Ab, + RAIU, eye signs\|\|Antithyroids, RAI, Surgery\| \|Transient thyrotoxicosis\|\|Brief\|\|Small goiter\|\|Low Ab, no eye signs, RAIU=0\|\|Time, beta blocker, ? steroids\| \|Subacute thyroiditis\|\|Brief\|\|Tender goiter\|\|RAIU=0, elevated ESR, recent URI\|\|Nothing, NSAID, steroids\| \|Toxic multinodular goiter\|\|Prolonged, mild\|\|Nodular goiter\|\|Typical scan\|\|Antithyroids, RAI, surgery\| \|Iodide induced\|\|Recent, mild\|\|Nodular goiter, occ.normal\|\|Low RAIU, abnormal scan\|\|Antithyroids, KClO4, time, stop I source\| \|Toxic adenoma\|\|Prolonged, mild\|\|One nodule\|\|“Hot” nodule on scan\|\|Surgery, RAI, ? Sclerosis\| \|Thyroid carcinoma\|\|Recent\|\|Variable, metastases\|\|Functioning metastases\|\|Surgery + RAI\| \|Exogenous hormone\|\|Variable\|\|Small thyroid\|\|RAIU and TG low, psychiatric illness\|\|Withdrawal, counseling\| \|Hydatiform mole\|\|Recent, mild\|\|Goiter\|\|Pregnancy, bleeding,HCG\|\|Surgery, chemotherapy\| \|Choriocarcinoma\|\|Recent, mild\|\|Goiter\|\|Increased HCG\|\|Surgery, chemotherapy\| \|Excess TRH\|\|Goiter\|\|Poor response to TRH\|\|Not known\|\|?\| \|TSH-oma\|\|Prolonged\|\|Goiter\|\|Excess alpha, TSH, adenoma\|\|Op, somatostatin, thyroid ablation\| \|Pituitary T3 resistance\|\|Prolonged\|\|Goiter\|\|Elevated or normal TSH, no tumor, mod. thyrotox, no excess alpha\|\|? Triac, somatostatin, thyroid ablation, beta blocker\| \|Struma ovarii\|\|Variable\|\|+ / – goiter\|\|Positive scan or US\|\|Surgery\| \|Hamburger toxicosis\|\|Recent, self-limited\|\|Small gland, no eye signs\|\|Suppressed TSH and TG and RAIU\|\|Avoid neck meat trimmings\| \|Hyperemesis\|\|Onset first trimester\|\|Pregnancy, variably toxic\|\|UP FTI, Low TSH, High HCG\|\|ATD if severe, pregnancy termination\| \|TSH-R mutation\|\|Congenital\|\|Typical thyrotoxicosis\|\|+ FH, germline mutation\|\|Thyroid ablation\| \|Familial gestational hyperthyroidism\|\|Onset first trimester\|\|Severe hyperthyroidism\|\|+ FH, TSH-R mutation sensitizing to hCG\|\|ATD, Surgery\| \|Amiodarone\|\|Prolonged\|\|Thyroid usually enlarged. Often heart disease.\|\|Suppressed RAIU, nl or increased FTI, elevated T3\|\|ATD + KClO4,Prednisone, Surgery,iopanoic acid\| \|Interferon-alpha induced\|\|Induced by INF treatment of hepatitis C\|\|Clinically significant\|\|Often remits if IFN stopped.\| \|Treatment of HIV\|\|During T cell recovery\|\|Clinically significant\|\|With or without prior thyroid autoimmunity\|\|May need treatment\| \|Administration of CAMPATH\|\|During recovery of T cells\|\|Clinically significant\|\|With or without prior thyroid autoimmunity\|\|May need treatment\| \|Sunitinib therapy\|\|During tyrosine kinase therapy for cancer\|\|Clinically significant\|\|Usually induces hypothyroidism, rarely hyper\|\|May need treatment\| Subclinical hyperthyroidism It should be remembered that thyrotoxicosis is today not only a clinical but also a laboratory diagnosis. Consistent elevation of the fT4 , and the T3 level, and suppressed TSH, or only suppression of TSH, can indicate that thyrotoxicosis is present even in the absence of clear-cut signs or symptoms These elevations themselves may be a sufficient indication for therapy, especially in elderly patients with coincident cardiac disease(33a,b). Antithyroid drug treatment of patients with subclinical hyperthyroidism was found to result in a decrease in heart rate, decrease in number of atrial and ventricular premature beats, a reduction of the left ventricular mass index, and left ventricular posterior wall thickness, as well as a reduction in diastolic peak flow velocity. These changes are considered an argument for early treatment of subclinical hypothyroidism. Subclinical hyperthyroidism may disappear, evolve into Graves hyperthyroidism., or, with MNG, persist for long periods unchanged. Individuals of any age with consistent suppression of TSH should be fully evaluated to determine if evidence of hyperthyroidism is present, or there is coincident disease that might be aggrevated by hyperthyroidism. SCH with TSH of 0.2-0.3.5 may not need treatment. Individuals with TSH at or below 0.1uU/ml most likely will require treatment by one of the methods described b elow. Apathetic hyperthyroidism designates a thyrotoxic condition characterized by fatigue, apathy, listlessness, dull eyes, extreme weakness, often congestive heart failure, and low-grade fever.[ 34, 35] Often such patients have small goiters, modest tachycardia, occasionally cool and even dry skin, and few eye signs. The syndrome may, in some patients, represent an extreme degree of fatigue induced by long-standing thyrotoxicosis. Once the diagnosis is considered, standard laboratory tests should confirm or deny the presence of thyrotoxicosis even in the absence of classical symptoms and signs. Other diagnostic problems Two common diagnostic problems involve (1) the question of hyperthyroidism in patients with goiter of another cause, and (2) mild neuroses such as anxiety, fatigue states, and neurasthenia. Most patients with goiter receive a battery of examinations to survey their thyroid function at some time. Usually these tests are done more for routine assessment than because there is serious concern over the possibility of thyrotoxicosis. In the absence of significant symptoms or signs of hyperthyroidism and ophthalmologic problems, a normal FTI or TSH determination is sufficiently reassuring to the physician and the patient. Of course, the most satisfactory conclusion of such a study is the positive identification of an alternate cause for enlargement of the thyroid. Some patients complain of fatigue and palpitations, weight loss, nervousness, irritability, and insomnia. These patients may demonstrate brisk reflex activity, tachycardia (especially during examinations), perspiration, and tremulousness. In the abscence of thyrotoxicosis, the hands are more often cool and damp rather than warm and erythematous. Serum TSH assay should be diagnostic. Mild and temporary elevation of the FTI may occur if there is a transient depression of TBG production — for example, when estrogen administration is omitted. This problem is occasionally seen in hospital practice, usually involving a middle-aged woman receiving estrogen medication that is discontinued when the patient is hospitalized. Estrogen withdrawal leads to decreased TBG levels and a transiently elevated FTI. After two to three weeks, both the T4 level and the FTI return to normal ( Table -3). In the differential diagnosis of heart disease, the possibility of thyrotoxicosis must always be considered. Some cases of thyrotoxicosis are missed because the symptoms are so conspicuously cardiac that the thyroid background is not perceived. This is especially true in patients with atrial fibrillation. Many disorders may on occasion show some of the features of hyperthyroidism or Graves’ disease. In malignant disease, especially lymphoma, weight loss, low grade fever, and weakness are often present. Parkinsonism in its milder forms may initially suggest thyroid disease. So also do the flushed countenance, bounding pulse, thyroid hypertrophy, and dyspnea of pregnancy. Patients with chronic pulmonary disease may have prominent eyes, tremor, tachycardia, weakness, and even goiter from therapeutic use of iodine. One should remember the weakness, fatigue, and jaundice of hepatitis and the puffy eyes of trichinosis and nephritis. Cirrhotic patients frequently have prominent eyes and lid lag, and the alcoholic patient with tremor, prominent eyes, and flushed face may be initially suspected of having thyrotoxicosis. Distinguishing between Graves’ disease with extreme myopathy and myopathies of other origin can be clinically difficult. The term chronic thyrotoxic myopathy is used to designate a condition characterized by weakness, fatigability, muscular atrophy, and weight loss usually associated with severe thyrotoxicosis. Occasionally fasciculations are seen. The electromyogram result may be abnormal. If the condition is truly of hyperthyroid origin, the thyroid function tests are abnormal and the muscular disorder is reversed when the thyrotoxicosis is relieved. Usually a consideration of the total clinical picture and assessment of TSH and FTI are sufficient to distinguish thyrotoxicosis from polymyositis, myasthenia gravis, or progressive muscular atrophy. True myasthenia gravis may coexist with Graves’ disease, in which case the myasthenia responds to neostigmine therapy. (The muscle weakness of hyperthyroidism may be slightly improved by neostigmine, but never relieved.) Occasionally electromyograms, muscle biopsy, neostigmine tests, and ACH-receptor antibody assays must be used to settle the problem. TREATMENT OF THYROTOXICOSIS– SELECTION OF PRIMARY Three forms of primary therapy for Graves’ disease are in common use today: (1) destruction of the thyroid by 131-I; (2) blocking of hormone synthesis by antithyroid drugs; and (3) partial or total surgical ablation of the thyroid. Iodine alone as a definitive form of treatment has been used in the past, but is not used today because its benefits may be transient or incomplete and because more effective methods have become available. Iodine is primarily used now in conjunction with antithyroid drugs to prepare patients for surgical thyroidectomy when that plan of therapy has been chosen. Roentgen irradiation was also used in the past. Selection of therapy depends on a multiplicity of considerations [36.1]. Availability of a competent surgeon, for example, undue emotional concern about the hazards of 131-I irradiation, or the probability of adherence to a strict medical regimen might govern one’s decision regarding one program of treatment as opposed to another. All three methods provide satisfactory outcomes in over 90% of patients [36.2].. Fig. 2 Iodine-131 therapy is quick, easy, moderately expensive, avoids surgery, and is without significant risk in adults and probably late teenagers. The larger doses required to give prompt and certain control generally induce hypothyroidism, and low doses are associated with a frequent requirement for retreatment or ancillary medical management over one to two years. 131-I is used as the primary therapy in most persons over age 40 and in most adults above age 21 if antithyroid drugs fail to control the disease. Treatment of children with 131-I is less common, as discussed later. Surgery, which was the main therapy until 1950, has been to a major extent replaced by 131-I treatment. As the high frequency of 131-I induced hypothyroidism became apparent, some revival of interest in thyroidectomy occurred. The major advantage of surgery is that definitive management is often obtained over an 8- to 12-week period, including preoperative medical control, and many adult patients are euthyroid after operation. Its well-known disadvantages include expense, surgery itself, and the risks of recurrent nerve and parathyroid damage, hypothyroidism, and recurrence. Nevertheless, if a skillful surgeon is available, surgical management may be used as the primary or secondary therapy in many young adults, as the secondary therapy in children poorly controlled on antithyroid drugs, in pregnant women requiring excessive doses of antithyroid drugs, in patients with significant exophthalmos, and in patients with coincident suspicious thyroid nodules. Early total thyroidectomy has been recommended for treating older, chronically ill patients with thyrotoxic storm if high-dose thionamide treatment, iopanoic acid, and glucocorticoids fail to improve the patient’s condition within 12 – 24 hours (36.4). Two recent surveys reporting trends in therapeutic choices made by thyroidologists have been published . In Europe, most physicians tended to treat children and adults first with antithyroid drugs, and adults secondarily with 131-I or less frequently surgery. Surgery was selected as primary therapy for patients with large goiters. 131-I was selected as the primary treatment in older patients. Most therapists attempted to restore euthyroidism by use of 131-I or surgery. In the United States, 131-I is the initial modality of therapy selected by members of the American Thyroid Association for management of uncomplicated Graves’ disease in an adult woman . Two-thirds of these clinicians attempt to give 131-I in a dosage calculated to produce euthyroidism, and one-third plan for thyroid ablation. 131-I THERAPY FOR THYROTOXICOSIS OF GRAVES’ DISEASE In many thyroid clinics 131-I therapy is now used for most patients with Graves’ disease who are beyond the adolescent years. It is used in most patients who have had prior thyroid surgery, because the incidence of complications, such as hypoparathyroidism and recurrent nerve palsy, is especially high in this group if a second thyroidectomy is performed. Likewise, it is the therapy of choice for any patient who is a poor risk for surgery because of complicating disease. Treatment of children- The question of an age limit below which RAI should not be used frequently arises. With lengthening experience these limits have been lowered. Several studies with average follow-up periods of 12 – 15 years attest to the safety of 131-I therapy in adults [ 39- 41]. In two excellent studies treated persons showed no tendency to develop thyroid cancer, leukemia, or reproductive abnormalities, and their children had no increase in congenital defects or evidence of thyroid damage [ 42- 44]. Franklyn and co workers recently reported on a population based study of 7417 patients treated with 131-I for thyrotoxicosis in England [44.1]. They found an overall decrease in incidence of cancer mortality, but a specific increase in mortality from cancer of the small bowel (7 fold) and of the thyroid (3.25) fold. The absolute risk remains very low, and it is not possible to determine whether the association is related to the basic disease, or to radioiodine treatment. Although there is much less data on long term results in children, there is a increased use of this treatment in teenagers over age 15-18, as discussed below. The epidemic of thyroid cancer apparently induced by radioactive iodine isotopes in infants and children living around Chernobyl suggests caution in use of 131-I in younger children. Since the possibility of a general induction of cancer by 131-I is of central concern, it is interesting to calculate the risk in children using the data presented by Rivkees et al (44.2) who are proponents of use of RAI for therapy in young children..The risk of death from cancer due specifically to radiation exposure is noted by these authors to be 0.16%/rem for children, and the whole body radiation exposure from RAI treatment at age 10 to be 1.45 rem/mCi administered. Rivkees et al advise treatment with doses of RAI greater then 160 uCi/gram thyroid, to achieve a thyroidal radiation dose of at least 150Gy (about 15000 rads). Assuming a reasonable RAIU of 50% and gland size of 40 gm, the administered dose would thus be 40(gm) x 160uCi/gm x 2 (to account for 50% uptake) =12.8 mCi. Thus the long term cancer death risk would be 12.8 (mCi) x 1.45 rem (per mCi) x 0.16% (per rem) = 3%. For a dose of 15mCi the incremental risk a of cancer mortality would be 4% at age 5, 2% at age 10, and 1% at age 15 Whether or not accepting a specific 2-5% risk of death from cancer because of this treatment is of course a matter of judgment by the physician and family. However, this would seem to many persons to constitute a significant risk that should be avoided Low 131-I uptake- Certain other findings may dictate the choice of therapy. Occasionally, the 131-I uptake is significantly blocked by prior iodine administration. The effect of iodide dissipates in a few days after stopping exposure, but it may take 3-12 weeks for the effect of amiodarone or IV contrast dyes to be lost. One may either wait for a few days to weeks until another 131-I tracer indicates that the uptake is in the toxic range or use an alternative therapeutic approach such as antithyroid drugs. Sometimes a patient with thyrotoxicosis harbors a thyroid gland with a configuration suggesting the presence of a malignant neoplasm. These patients probably should have surgical exploration. While FNA may exclude malignancy, the safety of leaving a highly irradiated nodule in place for many years is not established. Currently few patients who will have RAI therapy are subjected to ultrasonagraphy or scintiscaning. However Stocker et al. found that 12% of Graves’ patients had cold defects on scan, and among these half were referred for surgery. Six of 22, representing 2% of all Graves’ patients, 15% of patients with cold nodules, 25% of patients with palpable nodules, and 27% of those going to surgery had papillary cancer in the location corresponding to the cold defect. Of these patients, one had metastasis to bone and two required multiple treatments with radioiodine. They argue for evaluating patients with a thyroid scintigram and further diagnostic evaluation of cold defects(201a). 131-I therapy causes an increase in titers of TSH-RAbs, and anti-TG or TPO antibodies, which reflects an activation of autoimmunity. It probably is due to release of thyroid antigens by cell damage, or possibly destruction of intrathyroidal T cells. Many thyroidologists are convinced that 131-I therapy can lead to exacerbation of infiltrative ophthalmopathy, perhaps because of this immunologic response. Tallstedt and associates published data indicating that 131-I therapy causes exacerbation of ophthalmopathy in nearly 25% of patients, while surgery is followed by this response in about half as many.The same group conducted a second randomized trial (96) with a follow-up of 4 yr. Patients with a recent diagnosis of Graves’ hyperthyroidism were randomized to treatment with iodine-131 (163 patients) or 18 months of medical treatment (150 patients). Early substitution with T4 was given in both groups.: Worsening or development of eye problems was significantly more common in the iodine-131 treatment group (63 patients; 38.7%) compared with the medical treatment group (32 patients; 21.3%) (P < 0.001) (201b, 201c) Thus, as described below, patients with significant ophthalmopathy may receive corticosteroids along with131-I, or may be selected for surgical management. The indications and contraindications for 131-I therapy are given in Table 5. \|Table 5. Iodine-131 Therapy for Graves’ Disease\| SELECTION OF 131-I Dosage There are two basically different goals in 131-I dose selection. The traditional approach has been to attempt to give the thyroid 1)sufficient radiation to return the patient to euthyroidism, but not induce hypothyroidism.An alternative approach is to intend to 2) induce hypothyroidism, or euthyroidism and avoid any possible return of hyperthyroidism. Background-The dosage initially was worked out by a trial-and-error method and by successive approximations. By 1950, the standard dose was 160 uCi 131 I per gram of estimated thyroid weight. Of course, estimating the weight of the thyroid gland by examination of the neck is an inexact procedure, but can now be made more accurate by use of ultrasound. Also, marked variation in radiation sensitivity no doubt exists and cannot be estimated at all. It was gratifying that in practice this dosage scheme worked well enough. In the early 1960s, it was recognized that a complication of RAI therapy was a high incidence of hypothyroidism. This reached 20 – 40% in the first year after therapy and increased about 2.5% per year, so that by 10 years 50 – 80% of patients had low function . In an effort to reduce the incidence of late hypothyroidism, Hagen and colleagues reduced the quantity of 131-I to 0.08 mCi per gram of estimated gland weight . No increase was reported in the number of patients requiring retreatment, and there was a substantial reduction in the incidence of hypothyroidism. Most of these patients were maintained on potassium iodide for several months after therapy, in order to ameliorate the thyrotoxicosis while the radioiodine had its effect [ 49, 50]. Patients previously treated with 131-I are sensitive to and generally easily controlled by KI. However KI often precipitates hypothyroidism in these patients, which may revert to hyperthyroidism when the KI is discontinued. Over the years some effort was made to refine the calculation. Account was taken of uptake, half-life of the radioisotope in the thyroid, concentration per gram, and so on, but it is evident that the result in a given instance depends on factors that cannot be estimated precisely [46, 47]. One factor must be the tendency of the thyroid to return to normal if a dose of radiation is given that is large enough to make the gland approach, for a time, a normal functional state.In many patients, “cure” is associated with partial or total thyroid ablation. Although we, and many endocrinologists, attempt to scale the dose to the particular patient, some therapists believe it is futile, advocate giving up this attempt, and provide a standard dose giving up to 10000 rads to the thyroid(47.1). Leslie et al reported a comparison of fixed dose treatment and treatment adjusted for 24 hour RAIU, using low or high doses, and found no difference in outcome in either rate of control or induction of hypothyroidism on comparison of the methods. They favor the use of a fixed dose treatment with a single high or low dose (47.2). Many attempts have been made to improve the therapeutic program by giving the RAI in smaller doses. Reinwein et al . studied 334 patients several years after they had been treated with serial doses of less than 50 uCi 131-I per gram of estimated thyroid weight. One-third of these patients had increased levels of TSH, although they were clinically euthyroid. Only 3% were reported to be clinically hypothyroid. Dosage adjustmentsmade to induce euthyroidism usually include a factor for gland size, a standard dose in microCuries per gram, and a correction to account for 131-I uptake . A“Low Dose Protocol” was designed to compensate for the apparent radiosensitivity of small glands and resistance of larger glands . Using this approach, after one year, 10% of patients were hypothyroid, 60% are euthyroid, and 30% remained intrinsically toxic , although euthyroid by virtue of antithyroid drug treatment. At ten year follow-up, 40% were euthyroid and 60% hypothyroid. A problem with low-dose therapy is that about 25% of patients require a second treatment and 5% require a third. Although this approach reduces early hypothyroidism, it does so at a cost in time, money and patient convenience (Fig. 2). To answer these problems, patients can be re-treated, if need be, within six months, and propranolol and antithyroid drugs can be given between 131-I doses if needed. Unfortunately, experience shows that even low-dose 131-Itherapy is followed by a progressive development of hypothyroidism in up to 40 – 50% of patients ten years after therapy[ 54- 57]. \|Table 6. LOW Dosage Schedule for 131-I Therapy\| Thyroid wt. in gms. uCi retained/gm thyroid at 24h Thyroid rads, avg. Impressed by the need to retreat nearly a third of patients, a “Moderate Dose Protocol” was developed Table -6). This is a fairly conventional program with a mean dose of about 9 mCi. The 131-I dosage is related to gland weight and RAIU and is increased as gland weight increases. The calculation used is as follows: uCi given = (estimated thyroid weight in grams) X (uCi/g for appropriate weight from Table) / (fractional RAIU at 24 hours) (For readers who may find difficult the conversion of older units in Curies, rads, and rems to newer units of measurement, see Table -7.) Table 6. MODERATE Dosage Schedule for 131-I Therapy Thyroid wt. in gms. uCi retained/gm thyroid at 24h Thyroid rads, avg. \|Table 7. Conversion of International Units of Measurement\| \|Becquerel (Bq)\|\|2.7 x 10 -11Curies (1mCi=37MBq, 100mCi= 3.7GBq)\| \|Gray (Gy)\|\|100 rads ( 1 rad= 0.01Gy)\| \|Sievert (Sv)\|\|100 rems (1 rem = 0.01 Sv)\| Probably it is wise to do uptakes and treatment using either capsules or liquid isotope for both events. Rini et al have reported that RAIU done with isotope in a capsule appears to give significantly lower values (25 – 30% lower) than when the isotope is administered in liquid form, and this can significantly influence the determination of the dosage given for therapy(57.2). Berg et al report using a relatively similar protocol (absorbed doses of 100-120 Gy) and that 93% of their patients required replacement therapy after 1-5 years [57.1]. More recently two more studies have presented methods for more accurately delivering a specific radiation dose to the thyroid, and report curing up to 90% of patients, with low incidence of recurrence or hypothyroidism(57.3, 57.4). Franklyn and co-workers have recently analyzed their data on treatment of 813 hyperthyroid patients with radioactive iodide and corroborate many of the previously recognized factors involved in response. Lower dose (in this case 5 mCi), male gender, goiters of medium or large size and severe hyperthyroidism were factors that were associated with failure to cure after one treatment. They suggest using higher fixed initial doses of radioiodine for treating such patients (58.2), as do Leslie et al(58.4). Santos et al (58.4) compared fixed doses of 10 and 15mCi and found no difference in utcome at 12 months post treatment. These suggest a standard 10mCi dose, with the larger dose reserved for larger glands. Planned thyroid partial or complete ablation-All attempts to induce euthyroidism by a calculated moderate dose protocol end up with some patients hypothyroid, and others with persistent hyperthyroidism requiring further treatment. At this time many physicians giving 131-I therapy make no attempt to achieve euthyroidism, and instead use a dose sufficient to largely destroy the thyroid, followed by T4 replacement therapy . For example, a dose is given that will result in 7-20 mCi retained at 24 hrs, which is intended to induce hypothyroidism, accepting that in some (or many) patients this will ablate the thyroid completely. They argue that this is realistic and preferable since it offers 1) near certainty of prompt control, 2) avoids any chance of persistent or recurrent disease, 3)there is no benefit in having residual thyroid tissue, and 4) hypothyroidism is inevitable in most patients given RAI.Probably many patients given this treatment do in fact have some residual thyroid tissue that is either heavily damaged or reduced in amount so that it can not produce normal amounts of hormone. So far there is no evidence, in adults, that this residual radiated tissue will develop malignant change. There is no certainty at this time that one approach is better than the other. It may be worth remembering that over 50% of patients given calculated modereate dose therapy remain euthyroid after ten years and can easily be surveyed at yearly intervals for hypothyroidism. When giving large doses of 131-I it is prudent to calculate the rads delivered to the gland (as above), which can reach 40-50,000. Such large doses of radiation can cause clinically significant radiation thyroiditis, and occasionally damage surrounding structures. And lastly, a speculation. Practitioners comment that the incidence of serious ophthalmopathy seems to be less that in former decades. Prompt diagnosis and therapy might contribute to such a change. Another factor could be the more common ablation of the thyroid during therapy for Graves disease, since this should over time reduce exposure of patient’s immune system to thyroid antigens. Lithium with RAI therapy- Although rarely used, RAI combined with lithium is safe and more effective than RAI alone in the cure of hyperthyroidism due to Graves’ disease, probably because it it causes greater retention of RAI within the thyroid gland.. Bogazzi et al (58.21)reported a study combining lithium with RAI therapy. MMI treatment was withdrawn 5 days prior to treatment, Two hundred ninety-eight patients were treated with RAI plus lithium (900 mg/d for 12 d starting 5 days prior to 131-I treatment) and 353 with RAI alone. RAI dosage was 260mCi/g estimated thyroid weight, corrected for RAIU (done on lithium).. All patients receive prednisone 0.5mg/kg/day, beginning on day 7 after RAI, tapering over 2 months. Patients treated with RAI plus lithium had a higher cure rate (91.0%) than those treated with RAI alone (85.0%, P = 0.030). In addition, patients treated with RAI plus lithium were cured more rapidly (median 60 d) than those treated with RAI alone (median 90 d, P = 0.000). Treatment with lithium inhibited the serum FT4 increase seen after methimazole withdrawal and RAI therapy. Pretreatment with antithyroid drugs– Patients are often treated directly after diagnosis, without prior therapy with antithyroid drugs. This is safe and common in patients with mild hyperthyroidsm and especially those without eye problems. However often physicians give antithyroid drugs before 131-I treatment in order to deplete the gland of stored hormone and to restore the FTI to normal before 131-I therapy. This offers several benefits. The possibility of 131-I induced exacerbation of thyrotoxicosis is reduced, the patient recovers toward normal health, and there is time to reflect on the desired therapy and review any concerns about the use of radioisotope for therapy. If the patient has been on antithyroid drug, it is discontinued two days before RAIU and therapy. Patients can be treated while on antithyroid drug, but this reduces the dose retained, reduces the post-therapy increment in hormone levels, and reduces the cure rate, so seems illogical(58.31) . When antithyroid drugs are discontinued the patient’s disease may exacerbate, and this must be carefully followed. Beta blockers can be given in this interim, but there is no reason for a prolonged interval between stopping antithyroid drug, and 131-I therapy, unless there is uncertainty about the need for the treatment. Pretreatment with antithyroid drug does not appear in most studies to reduce the efficacy of 131-I treatment. but the debate about the effect of antithyroid drug pretreatment on the efficacy of radioactive iodine therapy continues. In a recent study in which patients were on or off antithyroid therapy, which was discontinued four days before treatment, there was no effect on the efficacy of treatment at a one year endpoint (59.2). In another study Bonnema et al found that PTU pretreatment , stopped 4 days prior to 131-I, reduced the efficacy of 131-I(59.4). Pretreatment is usually optional but is logical in patients with large glands and severe hyperthyroidism. Antithyroid drug therapy does reduce the pretreatment levels of hormone and reduces the rise in thyroid hormone level that may occur after radioactive iodide treatment. This certainly could have a protective effect in individuals who have coincident serious illness such as coronary artery disease, or perhaps individuals who have very large thyroid glands (59.3). It is indicated in two circumstances. In patients with severe heart disease, an 131-I- induced exacerbation of thyrotoxicosis could be serious or fatal. Pretreatment may reduce exacerbation of eye disease (see below), and it does reduce the post-RAI increase in antibody titers(59.1). The treatment dose of 131-I is best given as soon as possible after the diagnostic RAIU in order to reduce the period in which thyrotoxicosis may exacerbate without treatment, and since any intake of iodine (from diet or medicines or tests) would alter uptake of the treatment dose. Post 131-I treatment management– Many patients remain on beta-blockers but require no other treatment after 131-I therapy. Antithyroid drugs can be reinstituted after 5 ( or preferably 7 ) days, with minimal effect on retention of the treatment dose of 131-I. Alternatively, one may prescribe antithyroid drug (typically 10 mg methimazole q8h) beginning one day after administration of 131-I and add KI (2 drops q8h) after the second dose of methimazole. KI is continued for two weeks, and antithyroid drug as needed. This promotes a rapid return to euthyroidism, but by preventing recirculation of 131-I it can lower the effectiveness of the treatment. This method has been employed in a large number of patients, and is especially useful in patients requiring rapid control- for example, with CHF. A typical response is shown in Fig -3. It also has provided the largest proportion of patients remaining euthyroid at 10 years after therapy, in comparison to other treatment protocols. Glinoer and Verelst also report successful use of this strategy [59.1]. As noted, antithyroid drugs may be given starting 7-10 days after RAI without significantly lowering the radiation dose delivered to the gland. Treatment using 125-I was tried as an alternative to 131-I, because it might offer certain advantages . 125-I is primarily a gamma ray emitter, but secondary low-energy electrons are produced that penetrate only a few microns, in contrast to the high-energy beta rays of 131-I. Thus, it might theoretically be possible to treat the cytoplasm of the thyroid cell with relatively little damage to the nucleus. Appropriate calculations indicated that the radiation dose to the nucleus could be perhaps one-third that to the cytoplasm, whereas this difference would not exist for 131-I. Extensive therapeutic trials have nonetheless failed to disclose any advantage thus far for 125I. Larger doses — 10-20 mCi — are required, increasing whole body radiation considerably [ 61, 62]. SAFETY PRECAUTIONS AFTER 131-I THERAPY Doses of 131-I up to 33 mCi can be given to an outpatient basis, and this level is rarely exceeded in treatment of Graves’ disease. However patients must be given advice (written if possible) on precautions to be followed to prevent unneccessary or excessive exposure of other individuals to radiaactivity administered to the patient. For maximum safety, patients who have received 20 mCi should avoid extended time in public places for 1 day, maximize distance (6 feet) from children and pregnant women for 2 days, may return to work after 1 day, sleep in a separate (6-feet separation) bed from adults for 8 days, sleep in a separate bed from pregnant partners, infant, or child for 20 days, and avoid contact with body fluids (saliva, urine) for at least one week. Lower therapeutic doses require proportionally more moderate precautions.This topic is well covered in an article by Sisson et al (http://www.ncbi.nlm.nih.gov/pubmed/21417738).) Course After Treatment- If adequate treatment has been given, the T4 level falls progressively, beginning in one to three weeks.. Labeled thyroid hormones, iodotyrosines, and iodoproteins appear in the circulation . TG is released, starting immediately after therapy. Another iodoprotein, which seems to be an iodinated albumin, is also found in plasma. This compound is similar or identical to a quantitatively insignificant secretion product of the normal gland. It comprises up to 15% or more of the circulating serum 131-I in thyrotoxic patients . It is heavily labeled after 131-I therapy, and its proportional secretion is probably increased by the radiation. Iodotyrosine present in the serum may represent leakage from the thyroid gland, or may be derived from peripheral metabolism of TG or iodoalbumin released from the thyroid. The return to the euthyroid state usually requires at least two months, and often the declining function of the gland proceeds gradually over six months to a year. For this reason, it is logical to avoid retreating a patient before six months have elapsed unless there is no evidence of control of the disease. While awaiting the response to131-I the symptoms may be controlled by propranolol, antithyroid drugs, or iodide. Hypothyroidism develops transiently in 10 – 20% of patients, but thyroid function returns to normal in most of these patients in a period ranging from three to six months. These patients rarely become toxic again. Others develop permanent hypothyroidism and require replacement therapy. It is advantageous to give the thyroid adequate time to recover function spontaneously before starting permanent replacement therapy. This can be difficult for the patient unless partial T4replacement is given. Unfortunately, one of the common side effects of treating hyperthyroidism is weight gain, averaging about 20 lbs through four years after treatment (64a). Patients may develop transient increases in FTI and T3 at 2-4 months after treatment [63.1], sometimes associated with enlargement of the thyroid. This may represent an inflammatory or immune response to the irradiation, and the course may change rapidly with a dramatic drop to hypothyroidism in the 4-5th month. Hypothyroidism may ultimately be inescapable after any amount of radiation that is sufficient to reduce the function of the hyperplastic thyroid to normal . Many apparently euthyroid patients (as many as half) have elevated serum levels of TSH long after 131-I therapy, with “normal” plasma hormone levels . An elevated TSH level with a low normal T4level is an indicator of changes progressing toward hypothyroidism . The hypothyroidism is doubtless also related to the continued autoimmune attack on thyroid cells. Hypofunction is a common end stage of Graves’ disease independent of 131-I use; it occurs spontaneously as first noted in 1895(!) and in patients treated only with antithyroid drugs . Just as after surgery, the development of hypothyroidism is correlated positively with the presence of antithyroid antibodies. During the rapid development of postradiation hypothyroidism, the typical symptoms of depressed metabolism are evident, but two rather unusual features also occur. The patients may have marked aching and stiffness of joints and muscles. They may also develop severe centrally located and persistent headache. The headache responds rapidly to thyroid hormone therapy and suggests physiologic swelling of the pituitary. Hair loss can also be dramatic at this time. In patients developing hypothyroidism rapidly, the plasma T4 level and FTI accurately reflect the metabolic state. However, it should be noted that the TSH response may be suppressed for weeks or months by prior thyrotoxicosis; thus, the TSH level may not accurately reflect hypothyroidism in these persons and should not be used in preference to the FTI or FT4. If permanent hypothyroidism develops, the patient is given replacement hormone therapy and is impressed with the necessity of taking the medication for the remainder of his or her life. Thyroid hormone replacement is not obligatory for those who develop only temporary hypothyroidism, although it is possible that patients in this group should receive replacement hormone, for their glands have been severely damaged and they are likely to develop hypothyroidism at a later date. Perhaps these thyroids, under prolonged TSH stimulation, may tend to develop adenomatous or malignant changes, but this has not been observed. Many middle-aged women gain weight excessively after radioactive iodide treatment of hyperthyroidism. Usually such patients are on what is presumed to be appropriate T4 replacement therapy. Tigas et al note that such weight gain is less common after ablative therapy for thyroid cancer, in which case larger doses of thyroxine are generally prescribed. Thus they question whether the excessive weight gain after radioactive iodide treatment of Graves’ disease is due to the fact that insufficient thyroid hormone is being provided, even though TSH is within the “normal” range. They suggest that restoration of serum TSH to the reference range by T4 alone may not constitute adequate hormone replacement [ 69a]. Permanent replacement therapy (regardless of the degree of thyroid destruction) for children who receive 131-I has a better theoretical basis. In these cases, it is advisable to prevent TSH stimulation of the thyroid and so mitigate any tendency toward carcinoma formation. Exacerbation of thyrotoxicosis- During the period immediately after therapy, there may be a transient elevation of the T4 or T3 level , but usually the T4 level falls progressively toward normal. Among treated hyperthyroid patients with Graves’ disease, only rare exacerbations of the disease are seen. These patients may have cardiac problems such as worsening angina pectoris, congestive heart failure, or disturbances of rhythm such as atrial fibrillation or even ventricular tachycardia. Radiation-induced thyroid storm and even death have unfortunately been reported [71- 73]. These untoward events argue for pretreatment of selected patients who have other serious illness, especially cardiac disease, with antithyroid drugs prior to 131-I therapy. Other Problems Associate With 131-I Therapy The immediate side effects of 131-I therapy are typically minimal. As noted above, transient exacerbation of thyrotoxicosis can occur, and apparent thyroid storm has been induced within a day (or days) after 131-I therapy. A few patients develop mild pain and tenderness over the thyroid and, rarely, dysphagia. Some patients develop temporary hair loss, but this condition occurs two to three months after therapy rather than at two to three weeks, as occurs after ordinary radiation epilation. Hair loss also occurs after surgical therapy, so that it is a metabolic rather than a radiation effect. If the loss of hair is due to the change in metabolic status, it generally recovers in a few weeks or months. However hair thinning, patchy alopecia, and total alopecia, are all associated with Graves’ Disease, probably as another auto-immune processes. In this situation the prognosis for recovery is less certain, and occasionally some other therapy for the hair loss (such as steroids) is indicated. Permanent hypoparathyroidism has been reported very rarely as a complication of RAI therapy for heart disease and thyrotoxicosis[ 74- 76]. Patients treated for hyperthyroidism with 131-I received approximately 39 microGy/MBq administered (about 0.144rad/mCi) of combined beta and gamma radiation to the testes. This is reported to cause no significant changes in FSH, but testosterone declines transiently for several months, and there is no variation in sperm motility or % abnormal forms (76.1). Long term studies of patients after RAI treatment by Franklyn et al (76a) show a slight increase in mortality which appears to be related to cardiovascular disease, possibly related to periods of hypothyroidism. Worsening of ophthalmopathy after RAI– -In contrast to the experience with antithyroid drugs or surgery, antithyroid antibodies including TSAb levels increase after RAI [ 77, 78]. (Fig. 11-4, above). Coincident with this condition, exophthalmos may be worsened .(Fig. 11-5, below). This change is most likely an immunologic reaction to discharged thyroid antigens.The relationship of radiation therapy to exacerbation of exophthalmos has beem questioned , but much recent data indicates that there is a definite correlation[ 80, 80.1, 80.2]. Many therapists consider “bad eyes” to be a relative contraindication to RAI. Pretreatment with antithyroid drugs has been used empirically in an attempt to prevent this complication. Its benefit, if any, may be related to an immunosuppressive effect of PTU, described below. Treatment with methimazole before and for three months after I-131 therapy has been shown to help prevent the treatment-induced rise in TSH-R antibodies which is otherwise seen. Prophylaxis with prednisone with 131-I helps prevent exacerbation of exophthalmos, and this approach is now the standard approach in patients who have significant exophthalmos at the time of treatment [ 82, 82.1]. (Fig. 6, below) The recommended dose is 30 mg/day for one month, tapering then over 2-3 months. Of course prednisone or other measures can be instituted at the time of any worsening of ophthalmopathy. In this instance doses of 30-60 mg/day are employed, and usually are required over several months. While treatment with prednisone helps prevent eye problems, it does not appear to reduce the effectiveness of RAI in controlling the hyperthyroidism(82.3). Thyroidectomy, with total removal of the gland, should be considered for patients with serious active eye disease. Operative removal of the thyroid is followed by gradual diminution is TSH-R antibodies.(82.2 ), and as shown by Tallstedt is associated with a lower incidence of worsening eye problems than is initial RAI treatment. Several studiesdoc ument better outcomes in patients with GO who hav e total thyropidectomy vs those treated by other means(82.4, 82.5). Failure of 131-I to cure thyrotoxicosis in 2 or 3 treatments occurs occasionally, and rarely 4 or 5 therapies are given. The reason for this failure is usually not clear. The radiation effect may occur slowly. A large store of hormone in a large gland may be one cause of a slow response. Occasional glands having an extremely rapid turnover of 131-I require such high doses of the isotope that surgery is preferable to continued 131-I therapy and its attendant whole body radiation. If a patient fails to respond to one or two doses of 131-I, it is important to consider that rapid turnover may reduce the effective radiation dose. Turnover can easily be estimated by measuring RAIU at 4, 12, 24, and 48 hours, or longer. The usual combined physical and biological half-time of 131-I retention is about 6 days. This may be reduced to 1 or 2 days in some cases, especially in patients who have had prior therapy or subtotal thyroidectomy. If this rapid release of 131-I is found, and 131-I therapy is desired, the total dose given must be increased to compensate for rapid release. A rough guide to this increment is as follows: Increased dose = usual dose X ( (usual half time of 6 days) / (observed half time of “X” days) ) Most successfully treated glands return to a normal or cosmetically satisfactory size. Some large glands remain large, and in that sense may constitute a treatment failure. In such a situation secondary thyroidectomy could be done, but it is rarely required in practice. Long term care- Patients who have been treated with RAI should continue under the care of a physician who is interested in their thyroid problem for the remainder of their lives. The first follow-up visit should be made six to eight weeks after therapy. By this time, it will often be found that the patient has already experienced considerable improvement and has begun to gain weight. The frequency of subsequent visits will depend on the progress of the patient. Symptoms of hypothyroidism, if they develop, are usually not encountered until after two to four months, but one of the unfortunate facts of RAI therapy is that hypothyroidism may occur almost any time after the initial response. HAZARDS OF 131-I TREATMENT In the early days of RAI treatment for Graves’ disease, only patients over 45 years of age were selected for treatment because of the fear of ill effects of radiation. This age limit was gradually lowered, and some clinics, after experience extending over nearly 40 years, have now abandoned most age limitation. The major fear has been concern for induction of neoplasia, as well as the possibility that 131-I might induce undesirable mutations in the germ cells that would appear in later generations. \|Table 8. Gonadal Radiation Dose (in Rads) From Diagnostic Procedures and 131-I Therapy\| \|131-I-therapy, 5mCi\|\|usually <1.6\|\|usually <1.6\| \|Adapted from Robertson and Gorman \| Radiation is known to induce tumor formation in many kinds of tissues and to potentiate the carcinogenic properties of many chemical substances. Radiation therapy to the thymus or nasopharyngeal structures plays an etiologic role in thyroid carcinoma both in children and in adults[ 83- 85]. 131-I radiation to the animal thyroid can produce tumors, especially if followed by PTU therapy . Cancer of the thyroid has appeared more frequently in survivors of the atomic explosions at Hiroshima and Nagasaki than in control populations . Thyroid nodules, some malignant, have appeared in the natives of Rongelap Island as the result of fallout after a nuclear test explosion in which the radiation cloud unexpectedly passed over the island . Thyroid cancer following 131-I treatment? The experience at 26 medical centers with thyroid carcinoma after 131-I therapy was collected in a comprehensive study of the problem. A total of 34,684 patients treated in various ways were included. Beginning more than one year after 131-I therapy, 19 malignant neoplasms were found; this result did not differ significantly from the frequency after subtotal thyroidectomy. Thyroid adenomas occurred with increased frequency in the 131-I treated group, and the frequency was greatest when the patients were treated in the first two decades of life . Holm et al have thoroughly examined the history of a large cohort of 131-I-treated patients in Sweden and similarly found no evidence for an increased incidence of thyroid carcinoma or other tumors. For reasons that are not clear, the injury caused by 131-I therapy for Graves’ disease seems to induce malignant changes infrequently.. This result may occur because the treatment has largely been given to adults with glands less sensitive to radiation, because damage from 131-I therapy is so severe that the irradiated cells are unable to undergo malignant transformations, or because all cells are destroyed, or possibly because of the slow rate at which the dose is delivered . In up to one-half of patients followed for 5-10 years, there may be no viable thyroid cells remaining. We note that two studies reported above extend through an average follow-up period of 15 years. As described above [44.1], a recent report by Franklyn and coworkers indicated that there is an increased (3.25 fold) risk of mortality from cancer of the thyroid (and also bowel) after RAI, detected in along term follow up of a very large patient cohort. However it remains uncertain that this is related to hyperthyroidism per se, or radioiodine therapy. While these data are reassuring in regard to 131-I use in adults, Chernoby made it clear that its use in children can not be considered safe. Children in the area surrounding Chernobyl have developed a hugely increased incidence of thyroid carcinoma predominately due to ingestion of iodine-131 [89.1]. The latency has been about 5 years, and younger children are most affected. Risk is probably linearly related to dose. It is apparent that low doses, possibly down to 20 rads, produce malignan change in children(89.2).Risk of carcinogenesis decreases with increasing age at exposure, and is much less common after age 12. However some data indicates that an increased incidence of thyroid carcinoma is seen even among adults exposed at Chernobyl. Leukemia The incidence of leukemia among patients treated with RAI for Graves’ disease has not exceeded that calculated from a control group . This problem was also studied by the consortium of 26 hospitals . The incidence of leukemia in this group was slightly lower than in a control group treated surgically, but slightly higher in the latter surgical group than in the general population. In the group of RAI-treated patients, there has been no evidence of genetic damage, although, as will shortly be seen, this problem cannot be disregarded. In the United States, about 100 x 106 children will be born to a population of over 200 x 106 persons. Approximately 4% of these children will have some recognizable defect at birth. Of these, about one-half will be genetically determined or ultimately mutational, and represent the the effects of the baseline mutation rate in the human species. These mutations are attributed in part to naturally occurring radiation. All penetrating radiation, from whatever sources, produces mutations. The effects may vary with rate of application, age of the subject, and no doubt many other factors, and are partially cumulative. Nearly all of these mutations behave as recessive genetic factors; perhaps 1% are dominant. Almost all are minor changes, and those produced by experimental radiation are the same as those produced by natural radiation. Whether or not mutations are bad is in essence a philosophic question. Most of us would agree that the cumulative effect of mutations over past eras brought the human race to its present stage of development. However, most mutations, at least those that are observable, are detrimental to individual human adaptation to the present environment. In terms of the human population as a whole, detrimental mutant genes must be eliminated by the death of the carrier. We can agree that an increase in mutation rate is not desirable. It is hardly worth considering the pros and cons of the already considerable spontaneous mutation rate. In mice, the occurrence of visible genetic mutations in any population group is probably doubled by acute exposure of each member of the group over many generations to about 30 – 40 rads, and by chronic exposure to 100 – 200 rads . This radiation dosage is referred to as the doubling dose. Ten percent of this increase might be expressed in the first-generation offspring of radiated parents, the remainder gradually appearing over succeeding generations. The change in mutation rate in Drosophila is in proportion to the dosage in the range above 5 rads. Data from studies of mice indicate that at low exposures (from 0.8 down to 0.0007 rads/min), the dose causing a doubling in the spontaneous rate of identifiable mutations is 110 rads . Linearity, although surmised, has not been demonstrated at lower doses. At present, residents of the United States receive about 300 mrad/year, or 9 rad before age 30, the median parental age. Roughly half of this dose is from natural sources and half from medical and, to a lesser extent, industrial exposure. The National Research Council has recommended a maximum exposure rate for the general population of less than 10 rad above background before age 30. (The present level may therefore approach this limit.) The radiation received by the thyroid and gonads during 131-I therapy of thyrotoxicosis can be estimated from the following formula: Total beta radiation dose = 73.8 x concentration of 131-I in the tissue (µCi/g) x average beta ray energy (0.19 meV) x effective isotope half-life For illustration, we can assume a gland weight of 50 g, an uptake of 50% at 24 hours, a peak level of circulating protein-bound iodide (PB 131-I) of 1% dose/liter, an administered dose of 10 mCi, a thyroidal iodide biologic half-life of 6 days, and a gamma dose of about 10% of that from beta rays. On this basis, the thyroid receives almost 8200 rads, or roughly 1,600 rads/mCi retained. The gonadal dose, being about one-half the body dose, would approximate 4 rads, or roughly 0.4 rads/mCi administered. If the radiation data derived from Drosophila and lower vertebrates are applied to human radiation exposure (a tenuous but not illogical assumption), the increased risk of visible mutational defects in the progeny can be calculated. On the basis of administration to the entire population of sufficient 131-I to deliver to the gonads 2 rads or 2% of the doubling dose (assumed to be the same as in the mouse), the increase in the rate of mutational defects would ultimately be about 0.04%, although only one-tenth would be seen in the first generation. Obviously only a minute fraction of the population will ever receive therapeutic 131-I. The incidence of thyrotoxicosis is perhaps 0.03% per year, or 1.4% for the normal life span. At least one-half of these persons will have their disease after the childbearing age has passed. Although most of them will be women, this fact does not affect the calculations after a lapse of a few generations. Assuming that the entire exposed population receives 131-I therapy in an average amount of 5 mCi, the increase in congenital genetic damage would be on the order of 0.02 (present congenital defect rate) x 0.04 ( 131-I radiation to the gonads as a fraction of the doubling dose) x 0.014 (the fraction of the population ever at risk) x 0.5 (the fraction of patients of childbearing age) = 0.0000056. This crude estimate, developed from several sources, also implies that, if all patients with thyrotoxicosis were treated with 131-I, the number of birth defects might ultimately increase from 4 to 4.0006%. This increase may seem startlingly small or large, depending on one’s point of view, but it is a change that would be essentially impossible to confirm from clinical experience. Unfortunately, it is more difficult to provide a reliable estimate of the increased risk of genetic damage in the offspring of any given treated patient. Calculations such as the above simply state the problem for the whole population. Since most of the mutations are recessive, they appear in the children only when paired with another recessive gene derived from the normal complement carried by all persons. Assuming that only one parent received radiation from 131-I therapy amounting to 2% of the doubling dose, the risk of apparent birth defects in the patient’s children might increase from the present 4.0% to 4.008%. 0.02 (present genetic defect rate) x 0.04 (fraction of the doubling dose) x 0.1 (fraction of defects appearing in the first generation) = 0.00008, or an increase from 4.0% to 4.008%. Similar estimates can be derived by considering the number of visible mutations derived from experimental radiation in lower species.[ 92, 93] 6 x 10-8 (mutations produced per genetic locus per rad of exposure) x 104 (an estimate of the number of genetic loci in humans) x 2 (gonadal radiation in rads as estimated above) x 0.1 (fraction of mutations appearing in the first generation) = 0.00012 or 0.012% On this basis, the increase in the birth defect rate would be from 4.0% to 4.012%. One important observation stemming from these calculations is that large numbers of children born to irradiated parents must be surveyed if evidence of genetic damage is ever to be found. Reports of “no problems” among 30 to 100 such children are essentially irrelevant when one is seeking an increase in the defect rate of about 4.0% to about 4.008%. These statistics are presented in an attempt to give some quantitation to the genetic risk involved in 131-I therapy, and should not be interpreted as in any sense exact or final. The point we wish to stress is that radiation delivered to future parents probably will result in an increased incidence of genetic damage, but an increase so slight that it is difficult to measure. Nonetheless, the use of 131-I for large numbers of women who subsequently become pregnant will inevitably introduce change in the gene pool. In considering the significance of these risks, one must remember that the radiation exposure to the gonads from the usual therapeutic dose of 131-I may be only one or two times that produced during a procedure such as a barium enema [ 94, 95] and similar to the 10 rads received from a CAT scan. These examinations are ordered by most physicians without fear of radiation effect ( Table 11-8). When assessing the risks of 131-I therapy, one must, of course, consider the risks of any alternative choice of procedure. Surgery carries a small but finite mortality, as well as a risk of permanent hypoparathyroidism, hypothyroidism, and vocal cord paralysis. Some of these risks are especially high in children, the group in which radiation damage is most feared. Some physicians have held that 131-I therapy should not be given to patients who intend subsequently to have children. In fact, there is at present no evidence to support this contention, as discussed above. Chapman studied 110 women treated with 131-I who subsequently became pregnant and were delivered of 150 children. There was no evidence of any increase in congenital defects or of accidents of pregnancy. Sarkar et al also found no evidence of excess abnormalities among children who received 131-I therapy for cancer. Other studies have confirmed the apparent lack of risk[ 42, 43]. It should be noted that no increase in congenital abnormalities has been detected among the offspring of persons who received much larger radiation doses during atomic bomb explosions . Often the patient wishes to know about the possibility of carcinogenesis or genetic damage. These questions must be fully but delicately handled. It is not logical to treat a patient of childbearing age with 131-I and have the patient subsequently live in great fear of bearing children. These problems and considerations must be faced each time a patient is considered for RAI therapy. Pregnancy and 131-I Pregnancy is an absolute contraindication to 131-I therapy. The fetus is exposed to considerable radiation from transplacental migration of 131-I, as well as from the isotope in the maternal circulatory and excretory systems. In addition, the fetal thyroid collects 131-I after the 12th week of gestation and may be destroyed. The increased sensitivity of fetal structures to radiation damage has already been described. Physicians treating women of childbearing age with 131-I should be certain that the patients are not pregnant when given the isotope. Therapy during or immediately after a normal menstrual period or performance of a pregnancy test are appropriate precautions if pregnancy is possible. Women should be advised to avoid pregnancy for at least six months, since it usually takes this long to be certain that retreatment will not be needed. TREATMENT OF THYROTOXICOSIS WITH DRUGS Drug therapy for thyrotoxicosis was introduced by Plummer when he observed that the administration of iodide ameliorated the symptoms of this disease . (Fig 11-6). Administration of iodide has since been used occasionally as the complete therapeutic program for thyrotoxicosis, and widely as an adjunct in preparing patients for subtotal thyroidectomy. In 1941 the pioneering observations of MacKenzie and MacKenzie and Astwood led to the development of the thiocarbamide drugs, which reliably block the formation of thyroid hormones. It soon became apparent that, in a certain proportion of patients with Graves’ disease, use of these drugs could induce a prolonged or permanent remission of the disease even after the medication was discontinued. It is not yet understood why a temporary reduction in the formation of thyroid hormone should result in permanent amelioration of the disease. The antithyroid drug initially introduced for treatment of Graves’ disease was thiourea, but this drug proved to have a large number of undesirable toxic effects. Subsequently a number of derivatives and related compounds were introduced that have potent antithyroid activity without the same degree of toxicity. Among these substances are propyl- and methylthiouracil, methimazole, and carbimazole. In addition to this class of compounds, potassium perchlorate has been used in the treatment of thyrotoxicosis, but is infrequently employed for this purpose because of occasional bone marrow depression. This drug prevents the concentration of iodide by the thyroid. Beta adrenergic blockers such as propranolol have a place in the treatment of thyrotoxicosis. These drugs alleviate some of the signs and symptoms of the disease but have little or no direct effect on the metabolic abnormality itself. They do not uniformly induce a remission of the disease and can be regarded as adjuncts, not as a substitute for more definitive therapy. Mechanism of Action- Antithyroid drugs inhibit thyroid peroxidase, and PTU (not methimazole) has the further beneficial action of inhibiting T4 to T3 conversion in peripheral tissues. Antithyroid therapy is associated with a reduction in circulating antithyroid antibody titers , and anti-receptor antibodies [77, 78, 102]. Studies by MacGregor and colleagues indicate that antibody reduction also occurs during antithyroid therapy in patients with thyroiditis maintained in a euthyroid state, thus indicating that the effect is not due only to lowering of the FTI in Graves’ disease. These authors also found a direct inhibitory effect of PTU and carbimazole on antithyroid antibody synthesis in vitro and postulate that this is the mechanism for diminished antibody levels . Other data argue against this hypothesis [105, 105.1]. Antithyroid drug therapy is also associated with a prompt reduction in the abnormally high levels of activated T lymphocytes in the circulation ., although Totterman and co-workers found that this therapy caused a prompt and transient elevation of activated T suppressor lymphocytes in blood . During antithyroid drug treatment the reduced numbers of T suppressor cells present in most thyrotoxic patients return to normal[106, 108]. Antithyroid drugs do not directly inhibit T cell function . All of these data argue that antithyroid drugs exert a powerful beneficial immunosuppressive effect on patients with Graves’ disease. While much has been learned about this process, the exact mechanism remains uncertain. Evidence that antithyroid drugs exert their immunosuppressive effect by a direct inhibition of thyroid cell production of hormones has been reviewed by Volpe . Long-Term Antithyroid Drug Therapy with Thiocarbamides Propylthiouracil warning-Propylthiouracil and methimazole have for years been considered effectively interchangeable, and liver damage was considered a very rare problem. Recently a commission appointed by the FDA reevaluated this problem, and concluded that the rare but severe complications of liver failure needing transplantation, and death, were sufficient to contraindicate the use of PTU as the normal first-line drug (109.1). The Endocrine Society and other advisory groups have suggested that methimazole be used for treatment except in circumstances of inavailability of the drug, patient allergy, or pregnancy. Because of the association of scalp defects and probably a severe choanal syndrome with administration of methimazole during the first 12 weeks of pregnancy, current advice is to give PTU during the first trimester, and then switch to methimazole. Selection of patients- Many patients with Graves’ disease under age 40 – 45 are given a trial of therapy with one of the thiocarbamide drugs. Younger patients, and those with recent onset of disease, small goiters , and mild disease, are especially favorable candidates, since they tend to enter remission most frequently. It is generally found that one-fourth to one-third of these patients who satisfactorily complete a one year course have a long term or permanent remission. The remainder need repeated courses of drug therapy, must be maintained on the drug for years or indefinitely [111, 112], or must be given some other treatment. It appears that the percentage of patients responding has progressively fallen over the past years from about 50% to at present 25 – 30%[113, 114]. This change was thought to reflect an alteration in iodide in our diet , which increased from about 150 µg/day in 1955 to 300 – 600 µg/day. However other factors including greater precision in diagnosis and more complete data probably play major roles in establishing the response rate recognized at present. Many physicians do not consider antithyroid drug therapy to be the most efficacious means of treating thyrotoxic patients because of the high recurrence rate. Patients are initially given 100 – 150 mg PTU (if used) every 8 hours or 10 – 15 mg methimazole (Tapazole) every 12 hours. The initial dosage is varied depending on the severity of the disease, size of the gland, and medical urgency. Antithyroid drugs must usually be given frequently and taken with regularity since the half-time in blood is brief — 1.65 hours or less for PTU . Frequent dosage is especially needed when instituting therapy in a severely ill patient. Methimazole has the advantage of a longer therapeutic half-life, and appears to produce fewer reactions when given in low dosage. Propylthiouracil is preferred in patients with very severe hyperthyroidism and in pregnancy[117, 118] In most thyrotoxic patients, the euthyroid state, as assessed by clinical parameters, and FTI, can be reached within 4 – 6 weeks. If the patient fails to respond, the dosage may be increased. Iodine-131 studies may be performed to determine whether a sufficiently large dose of medication is being employed , but these studies are rarely needed. In general, it is assumed that binding of the should be nearly completely blocked, but the 24-hour 131-Ithyroid uptake in the patient under therapy may range from O% to 40%. This iodide is partly unbound and is usually released rapidly from the gland by administration of 1 g potassium thiocyanate or 400 mg potassium 131-I perchlorate. If perchlorate or thiocyanate does not discharge the iodide, it is obvious that binding of iodide is occurring despite the thiocarbamide therapy. The quantity of drug administered may then be increased. In experimental animals, the thiocarbamides block synthesis of iodothyronines more readily than they block formation of MIT and DIT. This observation suggests that a complete block in organification of iodide may not be necessary to produce euthyroidism. The patient’s thyroid might accumulate and organify iodide and form iodotyrosines, but be unable to synthesize the iodothyronines. Clinical observations to prove this point are not available. An RIA for PTU has been developed but has not proven useful in monitoring therapy . Doses of 300 mg PTU produced serum levels of about 7.1 µg/ml, and serum levels of PTU correlated directly with decreases in serum T 3 levels. It is theoretically possible to give therapeutic doses of methimazole by rectal administration in a saline enema or by suppository if the oral route is unavailable . Propylthiouracil has also been administered in suppositories or in enemas and found to be effective in treating hyperthyroidism. In a recent study PTU tablets were mixed in mineral oil, and then with cocoa butter, and frozen, to produce 1 gm suppositories each containing 400mg PTU. Suppositories given 4 times daily maintained a therapeutic blood level(121a). Jongjaroenprasert et al compared the effectiveness of a 400 mg dose of PTU in 90 ml of water vs. 400 mg of PTU given in polyethylene glycol suppositories. Both methods were effective treatments, but the enema appeared to provide greater bioavailability (121.1). Long Term Therapeutic Program After the initial period of high-dose therapy, the amount of drug administered daily is gradually reduced to a level that maintains the patient in a euthyroid condition, as assessed by clinical evaluation and serial observations of serum T4 , FTI, or T3 . These tests should appropriately reflect the metabolic status of the patient. Measurement of TSH level is useful when the FTI falls, to make sure that the patient has not been overtreated, but, as noted previously, TSH may remain suppressed for many weeks after thyrotoxicosis is alleviated. Serum T3 levels can also be monitored and are occasionally still elevated when the T4 level is in the normal range. During the course of treatment, the thyroid gland usually remains the same in size or becomes smaller. If the gland enlarges, the patient has probably become hypothyroid with TSH elevation; this condition should be ascertained by careful clinical and laboratory evaluation. If the patient does become hypothyroid, the dose of antithyroid drug should be reduced. Decrease in size of the thyroid under therapy is a favorable prognostic sign, and more often than not means that the patient will remain euthyroid after the antithyroid drugs have been discontinued. The dose is gradually reduced as the patient reaches euthyroidism, and often one-half or one-third of the initial dose is sufficient to maintain control. The interval between doses — typically 8-12 hours initially — can be extended, and patients can often be maintained on twice- or once-a-day therapy with methimazole . Alternatively, antithyroid drugs can be maintained at a higher dose, and thyroxine can be added to produce euthyroidism. Occasionally ingestion of large amounts of iodide interferes with antithyroid drug therapy. Duration of Treatment- The appropriate duration of antithyroid drug therapy is uncertain, but usually it is maintained for one year. Treatment for six months has been effective in some clinics but is not general practice . Longer treatment — such as one to three years — does gradually increase the percentage of responders , but this increase must be balanced against the added inconvenience to the patient [125, 126]. Azizi and coworkers have reported treatment of a group of 26 patients for ten years, during which time no serious problems occurred, and the cost approximated that of RAI therapy(126.1). At least one study suggests that treatment with large doses of antithyroid drugs may increase the remission rate, perhaps because of an immunosuppressive action . Body mass, muscle mass, and bone mineral content gradually recover, although bone mass remains below normal [125.1]. Risedronate treatment has been demonstrated to help restore bone mass in osteopenia/osteoporosis associated with Graves’ disease (125.2). After the patient has taken the antithyroid drugs for a year, the medication is gradually withdrawn over one to two months, and the patient is observed at intervals thereafter. Most of those who will ultimately have an exacerbation of the disease do so within three to six months; others may not develop recurrent hyperthyroidism for several years . Some patients may have a recurrence after discontinuing the drug that lasts for a short time, and then a remission without further therapy . An earlier report that administration of iodide increases the relapse rate after drug therapy is withdrawn has not been confirmed . Hashizume and co-workers reported that administration of T4 to suppress TSH for a year after stopping antithyroid drugs produced a very high remission rate . Similar results were found when T4 treatment was given after a course of antithyroid drugs during pregnancy. . These studies engendered much interest because of the uniquely high remission rate obtained by the continuation of thyroxine treatment to suppress TSH for a year or more after the usual course of antithyroid drug therapy. Possibly such treatment is beneficial since it inhibits the release of thyroid antigens. However subsequent studies have not found a beneficial effect of added T4 therapy [131.1,131.2]. It appears that the results are, for some reason, peculiar to this study group. The probability of prolonged remission correlates with reduction in gland size, disappearance of thyroid-stimulating antibodies from serum[132, 133], (Fig.11-8) return of T 3suppressibility, decrease in serum TG, and a haplotype other than HLA-DR3 [130, 136]. However, none of these markers predict recovery or continued disease with an accuracy rate above 60-70% [136.1]. Long after apparent clinical remission, many patients show continued abnormal thyroid function, including partial failure of T3 suppression, or absent or excessive TRH responses [127-140]. These findings probably indicate the tenuous balance controlling immune responses in these patients. Lactating women taking PTU have PTU levels of up to 7.7 µg/ml in blood, but in milk the level is much lower, about 0.7 µg/ml . Only 1-2 mg PTU could be transferred to the baby daily through nursing; this amount is inconsequential except for the possibility of reactions to the drug. Azizi et al. studied intellectual development of children whose mothers took methimazole during lactation, and found that there was no evident effect on physical and intellectual development, at least in children whose mothers took up to 20 mg of MMI daily [141a]. Hypothyroidism- It has long been known that some patients with Graves’ disease eventually develop spontaneous hypothyroidism . Reports have shown that most patients who become euthyroid after antithyroid drug therapy, if followed long enough, also develop evidence of diminished thyroid function . In a prospective study, Lamberg et al found that the annual incidence in these patients of subclinical hypothyroidism was 2.5%, and of overt hypothyroidism 0.6%. TOXIC REACTIONS TO ANTITHYROID DRUGS The use of antithyroid drugs may be accompanied by toxic reactions, depending on the drug and dose, in 3 – 12% of patients[ 117, 118, 142- 146]. Most of these reactions probably represent drug allergies[ 147- 148]. Chevalley et al., in a study of 180 patients given methimazole[ 143], found an incidence of toxicity of 4.3%, broken down as follows: Total reactions 4.3%; Pruritus 2.2%; Granulocytopenia 1.6%; Urticaria 0.5%.Methimazole may be the drug least likely to cause a toxic reaction, but there is little difference between it and PTU. When the antithyroid drugs are prescribed, the patient should be apprised of the possibility of reactions, and should be told to report phenomena such as a sore throat, fever, or rash to the physician and to discontinue the drug until the cause of the symptoms has been evaluated. These symptoms may herald a serious reaction. Allergic rash-If a patient taking a thiocarbamide develops a mild rash, it is permissible to provide an antihistamine and continue using the drug to see whether the reaction subsides spontaneously, as it commonly does. If the reaction is more severe or if neutropenia occurs, another drug should be tried or the medication withdrawn altogether. Usually a switch is made to another thiocarbamide, because cross-reactions do not necessarily occur between members of this drug family. Alternatively, the program of therapy may be changed to the use of RAI, which may be given after the patient has stopped taking the antithyroid drug for 48 – 74 hours, or the patient may be prepared for surgery by the administration of iodides and propranolol. The incidence of agranulocytosis in a large series of patients was 0.4% . It occurs most frequently in older patients and those given large amounts of the drug (20-30 mg methimazole every eight hours) . Reactions tend to be most frequent in the first few months of therapy but can occur at any time, with small doses of drug, and in patients of all ages . The most common reactions are fever and a morbilliform or erythematous rash with pruritus. Reactions similar to those of serum sickness, with migratory arthralgias, jaundice, lymphadenopathy, polyserositis, and episodes resembling systemic lupus erythematosus have also been observed . Pyoderma gangrenosum can occur (147.1). Neutropenia and agranulocytosis are the most serious complications. These reactions appear to be due to sensitization to the drugs, as determined by lymphocyte reactivity in vitro to the drugs . Occasionally agranulocytosis can develop even though the total WBC remains within normal ranges- a hazard to be remembered if differential counts are not done. Fortunately, even these problems almost always subside when the drug is withdrawn. Aplastic anemia with marrow hypoplasia has been reported (perhaps 10 cases), again with spontaneous recovery in 2-5 weeks in 70%, but fatal outcome in 3 patients . Thrombocytopenia and/or anemia may accompany the neutropenia. Vasculitis is a fortunately rare complication during treatment with antithyroid drugs. Neutropenia-It is probably wise to see patients receiving the thiocarbamides at least monthly during the initiation of therapy and every two to three months during the entire program. Neutropenia can develop gradually but often comes on so suddenly that a routine white cell count offers only partial protection. A white cell count must be taken whenever there is any suggestion of a reaction, and especially if the patient reports malaise or a sore throat. A white cell count taken at each visit will detect the gradually developing neutropenia that may occur. While many physicians do not routinely monitor these levels, the value of monitoring is suggested by the study of Tajiri et al . Fifty-five of 15398 patients treated with antithyroid drugs developed agranulocytosis, and 4/5 of these were detected by routine WBC at office visits. Low total leukocyte counts are common in Graves’ disease because of relative neutropenia, and for this reason a baseline WBC and differential should be performed before starting anti-thyroid drugs. However, total polymorphonuclear counts below 2,000 cells/mm3 should be carefully monitored; below 1,200 cells/mm3 it is unsafe to continue using the drugs. In the event of severe neutropenia or agranulocytosis, the patient should be monitored closely, given antibiotics if infection develops, and possibly adrenal steroids. There is no consensus on the use of glucocorticoids, since they have not been shown to definitely shorten the period to recovery. Administration of recombinant human granulocyte colony stimulating factor (75 µg/day given IM) appears to hasten neutrophile recovery in most patients who start with neutrophile counts > 0.1 X 109/L . Antithymocyte globulin and cyclosporin are also used [153.1]. Care must be taken to ensure against exposure to infectious agents, and some physicians prefer not to hospitalize their patients for this reason. If the patient is hospitalized, he or she should be placed in a special-care room with full bacteriologic precautions. Patients may develop antineutrophil cytoplasmic antibodies, either pericytoplasmic or cytoplasmic, during treatment, with or without vasculitis. Most cases appear to be associated with the use of propylthiouracil, and therapy includes cessation of the drug, sometimes treatment with steroids or cyclophosphamide for renal involvement, and rarely plasmapheresis. The commonest cutaneous lesion associated is leukocytoclastic vasculitis associated with purpuric lesions. Symptoms may include fever, myalgia, arthralgia, and lesions in the kidneys and lungs. Prognosis is usually good if the medication is discontinued, although death has occurred. ANCA positivity (pericytoplasmic, cytoplasmic, directed to myeloperoxidase, proteinase3, or human leukocyte elastase) can occur in patients on antithyroid drugs associated with vasculitis. It is also found without clinical evidence of vasculitis, and the significance of this finding is unclear [149.1]. Guma et al recently reported that, in a series of patients with Graves’ disease, 67% were found to be ANCA positive before medical treatment, and that 19% remained positive after one year of antithyroid treatment. This data suggests that ANCA antibodies reflect in some way the autoimmunity associated with Graves’ hyperthyroidism, rather than simply being a manifestation due to the treatment with antithyroid drugs (149.2). In addition to suppression of hematopoiesis and agranulocytosis, methimazole has been associated in one patient with massive plasmocytosis, in which 98% of the cells in the bone marrow were plasma cells. After discontinuation of the drug, and treatment with dexamethasone and G-CSF, the patient’s marrow recovered to normal (149.1). Liver damage-Thiocarbamides can also cause liver damage ranging from elevation of enzymes, through jaundice, to fatal hepatic necrosis Toxic hepatitis (primarily with propylthiouracil) and cholestatic jaundice (primarily with methimazole) are fortunately uncommon .Toxic hepatitis can be severe or fatal, but the incidence of serious liver complications is so low that routine monitoring of function tests has not been advised[ 151, 152]. Liver transplantation has been used with success in several patients [152.1]. As noted above,. Any sign of liver damage must be carefully monitored, and progress of abnormalities in liver function tests demand cessation of the drug[147, 152]. Diffuse interstitial pneumonitis has also been produced by propylthiouracil . Methimazole is best avoided in early pregnancy. Very rare cases of esophageal atresia, omphalocele, and choanal atresia occurred in Sweden almost only in infants whose mothers took methimazole during early pregnancy.This is thought to be a true, although fortunately very infrequent, complication of methimazole use. Their observations obviously suggest that methimazole should best not be given during early months of pregnancy (153.2). Potassium Perchlorate, Lithium,and Cholestyramine Potassium perchlorate was introduced into clinical use after it was demonstrated that several monovalent anions, including nitrates, have an antithyroid action. Perchlorate was the only member of the group that appeared to have sufficient potency to be useful. This drug, in doses of 200 – 400 mg every six hours, competitively blocks iodide transport by the thyroid. Accordingly, therapeutic doses of potassium iodide will overcome its effect. Institution and control of therapy with perchlorate are similar to those discussed for the thiocarbamides. Toxic reactions to this agent occur in about 4% of cases and usually consist of gastric distress, skin rash, fever, lymphadenopathy, or neutropenia; they usually disappear when the drug is discontinued. The reaction rate is higher when doses of more than 1 g/day are given . Nonfatal cases of neutropenia or agranulocytosis have been reported, and four cases of fatal aplastic anemia have been associated with the use of this drug . Because of toxic reactions, perchlorate is not used at present for routine therapy. It has found a role in therapy of thyrotoxicosis induced by amiodarone . Apparently blocking of iodide uptake is an effective antithyroid therapy in the presence of large body stores of iodide, while in this situation, methimazole and propylthiouracil are not effective alone. Lithium ion inhibits release of T4 and T3 from the thyroid and has been used in the treatment of thyrotoxicosis, but is most effective when used with a thiocarbamide drug. It does not have a well-established place in the treatment of Graves’ disease[ 157, 158]. It has possible value in augmenting the retention of 131-I and in preparing patients allergic to the usual antithyroid drugs or iodide for surgery, although propranolol is generally used for the latter problem. Cholestyramine (4gm, q8h) for a month has been shown to hasten return of T4 to normal [159.1] by binding hormone in the gut. It can be used as an adjunct to help speed return of hormone levels to normal, and may be especially beneficial in thyroid storm. Iodine - Plummer originally observed that the administration of iodide to thyrotoxic patients resulted in an amelioration of their symptoms. This reaction is associated with a decreased rate of release of thyroid hormone from the gland and with a gradual increase in the quantity of stored hormone. The effect of iodide on thyroid hormone release and concentration in blood is apparent in Figure 11-6. The mechanism of action may be by inhibition of generation of cAMP, and involves inhibition of proteolysis, but is not fully understood. Therapeutic quantities of iodide also have an effect on hormone synthesis through inhibition of organification of iodide. Iodide has similar but less intense effects on the normal thyroid gland, apparently because of adaptive mechanisms. Administration of large amounts of iodide to laboratory animals or humans blocks the synthesis of thyroid hormone and results in an accumulation of trapped inorganic iodide in the thyroid gland (the Wolff-Chaikoff effect, see Ch 2). The thyrotoxic gland is especially sensitive to this action of iodide. Raising the plasma iodide concentration to a level above 5 µg/dl results in a complete temporary inhibition of iodide organification by the thyrotoxic gland. In normal persons elevation of the inorganic 127-I level results, up to a point, in a progressive increase of accumulation of iodide in the gland. When the plasma concentration is above 20 µg/dl, organification is also inhibited in the normal gland . The sensitivity of the thyrotoxic gland, in comparison with that of the euthyroid gland, may be due to an increased ability to concentrate iodide in the thyroid, and its failure to “adapt” by decreasing the iodide concentrating mechanism. When iodine is to be used therapeutically in Graves’ disease, one usually prescribes a saturated solution of potassium iodide (which contains about 50 mg iodide per drop) or Lugol’s solution (which contains about 8.3 mg iodide per drop). Thompson and co- workers found that 6 mg of I- or KI produces a maximum response. This fact was reemphasized by Friend, who pointed out that the habit of prescribing the 5 drops of Lugol’s or SSKI three times daily is unnecessary . Two drops of Lugol’s solution or 1 drop of a saturated solution of potassium iodide two times daily is more than sufficient. The therapeutic response to iodide begins within two to seven days and is faster than can be obtained by any other methods of medical treatment. Only 3% of patients so treated fail to respond. Men, older persons, and those with nodular goiter are in the group less likely to have a response to iodide. Although almost all patients initially respond to iodide, about one-third respond partially and remain toxic, and another one-third initially respond but relapse after about six weeks . The use of iodide as definitive therapy for thyrotoxicosis has been discarded in favor of the modalities previously described. Iodides are sometimes given after 131-Itherapy to control hyperthyroidism, and are usually given as part of treatment before thyroidectomy. Adjunctive Therapy for Graves’ Disease Propranolol, metopranol, atenolol Beta-adrenergic blocking agents have won a prominent position in the treatment of thyrotoxicosis. Although they alleviate many of the signs and symptoms, they have little effect on the fundamental disease process[ 166, 167]. Palpitations, excessive sweating, and nervousness improve, and tremor and tachycardia are controlled. Many patients feel much improved, but others are depressed by the drug and prefer not to take it. Improvement in myocardial efficiency and reduction in the exaggerated myocardial oxygen consumption have been demonstrated . Propranolol lowers oxygen consumption and reverses the nitrogen wasting of thyrotoxicosis, although it does not inhibit excess urinary calcium and hydroxyproline loss . Propranolol is useful in symptomatic treatment while physician and patient are awaiting the improvement from antithyroid drug or 131-I therapy . Some patients appear to enter remission after using this drug alone for six months or so of therapy[ 169, 172]. It has been useful in neonatal thyrotoxicosis and in thyroid storm . The drug must be used cautiously when there is evidence of severe thyrotoxicosis, or heart failure, but often control of tachycardia permits improved circulation. Beta blockade can induce cardiovascular collapse in patients with or without heart failure, and asystolic arrest (174a,b). Administration of beta blocker was shown by Ikram to reduce CO by 13% in patients with uncontrolled CHF, and apparently this reduction in CO can be near fatal in rare patients. Some surgical groups routinely prepare patients for thyroidectomy with propranolol for 20 – 40 days and add potassium iodide during the last week . The BMR and thyroid hormone level remain elevated at the time of operation, but the patient experiences no problems. We prefer conventional preoperativepreparation with thiocarbamides, with or without iodide, and would use propranolol as an adjunct, or if the patient is allergic to the usual drugs. Propranolol is usually given orally as 20 – 40 mg every four to six hours, but up to 200 mg every six hours may be needed. In emergency management of thyroid storm (see also Chapter 12) or tachycardia, it may be given intravenously (1 – 3 mg, rarely up to 6 mg) over 3 – 10 minutes and repeated every four to six hours under electrocardiographic control. Atropine (0.5 – 1.0 mg) is the appropriate antidote if severe brachycardia is seen. Reserpine and Guanethidine Drugs such as reserpine and guanethidine that deplete tissue catecholamines were used extensively in the past as adjuncts in the therapy for thyrotoxicosis, but fell into disuse as the value of beta -sympathetic blockade with propranolol became recognized. Glucocorticoids, Ipodate, and Other Treatments As described elsewhere, potassium iodide acts promptly to inhibit thyroid hormone secretion from the Graves’ disease thyroid gland. PTU, propranolol, glucocorticoids , amiodarone, and sodium ipodate (Oragrafin Sodium) inhibit peripheral T4 to T3 conversion, and glucocorticoids may have a more prolonged suppressive effect on thyrotoxicosis . Orally administered resins bind T 4in the intestine and prevent recirculation . All of these agents have been used for control of thyrotoxicosis [ 184, 185]. Combined dexamethasone, potassium iodide, and PTU can lower the serum T3 level to normal in 24 hours, which is useful in severe thyrotoxicosis. Prednisone has been reported to induce remission of Graves’ disease, but at the expense of causing Cushing’s syndrome . Ipodate (0.5 – 1 g orally per day) acts to inhibit hormone release because of its iodine content, in addition to its action to inhibit T4 to T3 conversion. This dose of ipodate given to patients with Graves’ disease reduced the serum T3 level by 58% and the T 4level by 20% within 24 hours, and the effect persisted for three weeks[ 188, 189]. This dose of ipodate was more effective than 600 mg of PTU, which decreased the T3 level by only 23% during the first 24 hours, whereas the T4 level did not drop.Ipodate may prove to be a useful adjunct in the early therapy of hyperthyroidism, but will increase total body and thyroidal iodine. However, when the drug is stopped, the RAIU in Graves’ patients usually returns to pre- treatment levels within a week . Because it is the most effective agent available in preventing conversion of T4 to T3, it has a useful role in managing thyroid storm. Immunosuppressive Therapy- Development of new targeted and relatively safe immune suppressive treatments has allowed their extension to Graves’ disease. Rituximab, an anti CD20 B cell lymphocyte depleting monoclonal antibody, was initially found to induce remission in Graves’ ophthalmopathy. It also mediates decreases in anti thyroid antibodies, and is currently employed in a Phase II trial for therapy of mild, relapsing Graves’ disease (175.1, 175.2). Significant adverse events during therapy with rituximab (“serum sickness”, mild colitis, iridocyclitis, polyarthritis) have been reported, andwill probably limit its usefulness (175.21) Use of agents of this type, that work by increasing function of regulatory T cells, will probably become common in the next few years. Another approach has been pioneered by Gershengorn and colleagues, who devised a small molecule that is an “allosteric inverse agonist” of TSHR, and inhibits stimulation of TSH receptor activation by TSAbs (175.3 ) Subtotal thyroidectomy is an established and effective form of therapy for Graves’ disease, providing the patient has been suitably prepared for surgery. In competent hands, the risk of hypoparathyroidism or recurrent nerve damage is under 1%, and the discomfort and transient disability attendant upon surgery may be a reasonable price to pay for the rapid relief from this unpleasant disease. In some clinics it is the therapy of choice for most young male adults, especially if a trial of antithyroid drugs has failed. Total thyroidectomy may be preferred in patients with serious eye disease or high TRAb levels, in order to help the eye disease and to keep down the incidence of recurrence . iAs with other effective methods available, it is necessary for the physician and the patient to decide on the form of therapy most suitable for the case at hand. Because of the potential but unproved risks of 131-I therapy, it is not always possible to make an entirely rational choice; the fears and prejudices of the physician and the patient will often enter into the decision. Surgery is clearly indicated in certain patients. Among these are (1) patients who have not responded to prolonged antithyroid drug therapy, or who develop toxic reactions to the drug and for whatever reason are unsuitable for 131-I therapy; (2) patients with huge glands, which frequently do not regress adequately after 131-I therapy; and (3) patients with thyroid nodules that raise a suspicion of carcinoma. Stocker et al have reviewed the problem of nodules in Graves’ glands. They found that 12% of Graves’ patients had cold defects on scan, and among these half were referred for surgery. Six of 22, representing 2% of all Graves’ patients, 15% of patients with cold nodules, 25% of patients with palpable nodules, and 27% of those going to surgery, had papillary cancer in the location corresponding to the cold defect. Of these patients, one had metastasis to bone and two required multiple treatments with radioiodine. These authors argue for evaluating patients with a thyroid scintigram and further diagnostic evaluation of cold defects(201a). Subtotal or near total thyroidectomy is often the treatment of choice for patients with amiodarone induced thyrotoxicosis, since response to ATDs is typically poor, and RAIU can not be given. Surgery may also have a place in therapy of older patients with thyroid storm and/or cardio-respiratory failure, who do not respond rapidly to intensive medical therapy(202a). Surgery in patients with ophthalmopathy Contemporary data indicate that exophthalmos may be exacerbated by RAI therapy ,although in some studies appearance of progressive ophthalmopathy was about the same after treatment with 131-I as with surgery . Thus, in the presence of serious eye signs, treatment with antithyroid drugs followed by surgery is an important alternative to consider, and total thyroidectomy is preferred [ 201, 204]. The preferential use of surgery rather than radioactive iodide in the management of patients with severe Graves’ ophthalmopathy, and the greater, more frequent exacerbation of eye disease after RAI therapy, has been supported in a number of studies including those by Torring et al [204a], Moleti et al [204b], and De Bellis et al [204c]. Marcocci et al, in contrast, report that near-total thyroidectomy had no efffect on the course of ophthalmopathy in a group of patients who had absent or non-severe preexisting ophthalmopathy. The relevance of this to patients with more severe ocular disease is uncertain, since it is logical to expect that in these patients there would be no effect of removing antigens, if they lacked any tendency to develop ophthalmopathy [204d]. Moleti et al recently reported on 55 patients with Graves’ disease and mild to moderate Graves’ ophthalmopathy, who underwent near-total thyroidectomy, and of whom 16 had standard ablative doses of radioactive iodide. They found that the course of ophthalmopathy, both short and long term after treatment, was significantly better in the group of patients who underwent thyroidectomy and 131-I ablation, and suggest that this is a more effective means of inducing and maintaining ophthalmopathy inactive (204e). In a randomized, prospective study, total thyroidectomy, rather than partial thyroidectomy, was followed by a better outcome of GO in patients given iv glucocorticoids. Radioiodine uptake test and thyroglobulin assay showed complete ablation in the majority of total, but not of partial thyroidectomy patients (204g). The rate of patient rehabilitation is probably quickest with surgery. Although the source of hormone is directly and immediately removed by surgery, the patient usually must undergo one to three months of preparation before operation. The total time from diagnosis through operative convalescence is thus three to four months. Antithyroid drugs, in contrast, provide at best only 30 – 40% permanent control after one year of therapy. Iodine-131 can assuredly induce prompt remission. Low dose protocols, as noted, are plagued by a need for medical management and retreatment over one to three years before all patients are euthyroid. Treatment with higher doses provides more certain remission at the expense of hypothyroidism. There are several strong contraindications to surgery, including previous thyroid surgery, severe coincident heart or lung disease, the lack of a well-qualified surgeon, and pregnancy in the third trimester, since anesthesia and surgery may induce premature labor. More enthusiastic surgeons have in the past recommended surgery for all children as the initial approach, claiming that there is less interference with normal growth and development than with prolonged antithyroid drug treatment . Therapy for childhood thyrotoxicosis is discussed further below. Preparation for Surgery Antithyroid drugs of the thiocarbamide group are employed to induce a euthyroid state before subtotal thyroidectomy when surgery is the desired form of treatment. Two approaches are used. Mmethimazole (or PTU if used) may be administered until the patient becomes euthyroid. After this state has been reached, and while the patient is maintained on full doses of thiocarbamides, Lugol’s solution or a saturated solution of potassium iodide is administered for 7 – 10 days. This therapy induces an involution of the gland and decreases its vascularity, a factor surgeons find helpful in the subsequent thyroidectomy. In one study Lugol solution treatment resulted in a 9.3-fold decreased rate of intraoperative blood loss. Preoperative Lugol solution treatment decreased the rate of blood flow, thyroid vascularity measured by histomorphometry , and intraoperative blood loss during thyroidectomy(191.1). The iodide should be given only while the patient is under the effect of full doses of the antithyroid drug; otherwise, the iodide may permit an exacerbation of the thyrotoxicosis. Alternatively patients may be prepared by combined treatment with antithyroid drugs and thyroxine. It is not obvious that one method is superior to the other. Severely ill patients can be prepared for surgery rapidly by combining several treatments-iopanoic acid 500mg bid, dexamethasone 1mg bid, antithyroid drugs, and beta-blockers(204f). Pre-treatment should have the patient in optimal condition for surgical thyroidectomy. By this time the patient has gained weight, the nutritional status has been improved, and the cardiovascular manifestations of the disease are under control. At the time of surgery, the anesthesia is well tolerated without the risk of hypersensitivity to sympathoadrenal discharge characteristic of the thyrotoxic subject. The surgeon finds that the gland is relatively avascular. Convalescence is customarily smooth. The stormy febrile course characteristic of the poorly prepared patient in past years is rarely seen. Reactions to the thiocarbamide drugs occasionally occur during preparation for surgery. If the problem is a minor rash or low-grade fever, the drug is continued, or a change is made to a different thiocarbamide. More severe reactions (severe fever or rash, leukopenia, jaundice, or serum sickness) necessitate a change to another form of therapy, but no entirely satisfactory alternative is available. One course is to administer iodide and propranolol and proceed to surgery. In some patients, it is best to proceed directly to 131-I therapy if difficulties arise in the preparation with antithyroid drugs. Propranolol has been used alone or in combination with potassium iodide in preparation for surgery, and favorable results have generally been reported[193-195]. This procedure is doubtless safe in the hands of a medical team familiar and experienced with this protocol and willing to monitor the patient carefully to ensure adequate dosage. It is safe to use in young patients with mild disease, but is not advised as a standard protocol. Propranolol is used as an adjunct, or combined with potassium iodide as the sole therapy only when complications with antithyroid drugs preclude their use and surgery is strongly preferred to treatment with 131-I. Amiodarone induced hyperthyroidism is typically difficult to manage, as described in Chapter 13. Administration of iopanoic acid, 1 gm daily for 13 days, has been shown to provide successful pre-operative therapy, reducing T3 levels to normal (195a). Propranolol is the usual drug used for preparation of patients with amiodarone induced hyperthyroidism going to surgery. Surgical Techniques and Complications The standard operation is a one-stage subtotal thyroidectomy. General anesthesia is standard, but cervical plexus block and out-patient surgery is employed by some surgeons [192.1, 192.2]. The amount of tissue left behind is about 4-10 grams, but this amount is variable. Taylor and Painter found that the average volume of this remnant in 43 patients achieving a remission was about 8 ml, and Sugino et al recommended leaving 6 grams of tissue [196a]. The toxic state recurred in only two patients in their series, and in these twice the amount of tissue mentioned above was left. Ozaki also noted the importance of the amount of thyroid remaining as the principal predictor of eu- or hypo-thyroidism [196.1].There seems however to be no relation between the original size of the thyroid and the size of the remnant necessary to maintain normal metabolism. Motivated in part by economic considerations, there has been in recent years a reevaluation of thyroidectomy done under local anesthesia as a day-surgery proceedure. Pros and cons have recently been discussed [196.2]. In proper hands local anesthesia and prompt discharge seem acceptable, but most surgeons opt for the standard in hospital approach since it offers a more controlled operative setting and an element of safety the night after surgery. Some clinicians argue for total-thyroidectomy in an effort to reduce recurrence rates (196.3), and point out that this operation seems to reduce anti-thyroid autoimmunity and reduces the chance of exacerbation of ophthalmopathy. Permanent cure of the hyperthyroidism is produced in 90 – 98% of patients treated this way. Although surgery of the thyroid has reached a high degree of perfection, it is not without problems even in excellent hands. The complication rates at present are low . Among 254 patients operated on at three Nashville hospitals in the decade before 1970, there was no mortality, only minor wound problems, a 1.9% incidence of permanent hypoparathyroidism, and a 4.2% recurrence rate . Hypo-parathyroidism is the major undesirable chronic complication. Surgical therapy at the Mayo Clinic has in recent years been associated with a 75% rate of hypothyroidism but only a 1% recurrence rate, as an effort was made to remove more tissue and prevent recurrences. There is typically an inverse relationship between these two results of surgery. In the recent experience of the University of Chicago Clinics, the euthyroid state has been achieved by surgery in 82%; 6% became hypothyroid, and the recurrence rate was 12% . Palit et al. recently published a meta analysis of collected series of patients treated for Graves’ disease, either by total thyroidectomy or subtotal thyroidectomy. Overall, the surgery controlled hyperthyroidism in 92% of patients. There was no difference in complication rates between the two kinds of operations, with permanent laryngeal nerve injury occurring in 0.7 – 0.9% of patients, and permanent hypoparathyroidism in 1 – 1.6% of patients. Since many surgeons have become more familiar and capable with total thyroidectomy, and this avoids the possible recurrence of disease, although possibly slightly increasing the risk of nerve or parathyroid damage, total thyroidectomy has become a common or even preferred alternative to subtotal thyroidectomy for managing hyperthyroidism [200a]. Recurrence rates are higher in patients with progressive exophthalmos or positive assays for TRAb, suggesting that total thyroidectomy may be preferred in these cases . Geographic differences in iodine ingestion have been related to the outcome. In Iceland, with a high iodine intake, postoperative hypothyroidism is less frequent, but recurrence is more common than in iodine-deficient Scotland . Death rates are now approaching the vanishing point Of the nonfatal complications, permanent hypoparathyroidism is the most serious, and requires lifelong medical supervision and treatment. Experienced surgeons have an incidence under 1% . Unfortunately, the general experience is near 3%. More patients, perhaps 10%, develop transient post-operative hypocalcemia but soon recover apparently normal function. Perhaps these patients have borderline function that may fail in later years. Unilateral vocal cord paralysis rarely causes more than some hoarseness and a weakened voice, but bilateral injury leads to permanent voice damage even after corrective surgery. Bilateral recurrent nerve injury may be associated with severe respiratory impairment when an acute inflammatory process supervenes and may be life-threatening. Fortunately, it is now extremely rare after subtotal thyroidectomy. Damage to the superior external laryngeal nerve during surgery may alter the quality of the voice and the ability to shout without causing hoarseness. One may speculate whether declining skills in the techniques of subtotal thyroidectomy, attendant upon a dramatic fall in the use of this procedure, may lead to an increase in the hazards of the procedure. Hypothyroidism, whether occurring after surgery or 131-I therapy, can be readily controlled. Transient hypothyroidism is common, with recovery in one to six months. The presence of autoimmunity to thyroid antigens predisposes to the development of hypothyroidism after subtotal thyroidectomy for thyrotoxicosis. A positive test for antibodies to the microsomal/TPO antigen was found by Buchanan et al to correlate with an increased incidence of postoperative hypothyroidism. The incidence of hypothyroidism is certainly of importance in weighing the virtues of 131-I and surgical therapy. The ability of surgical therapy to produce a euthyroid state in many patients over long-term follow-up gives it one advantage over RAI therapy, but this must be weighed against the risk of hypoparathyroidism and recurrent nerve damage. Course After Surgery – In the immediate postoperative period, patients should be followed closely. They should ideally have a special duty nurse or family member providing watch during the first 24 hours, and a tracheotomy set and calcium chloride or gluconate for infusion should be at the bedside. During this period, undetected hemorrhage can lead to asphyxiation. Current use of drains with constant suction helps protect against this problem. Transient hypocalcemia is common, resulting from trauma to the parathyroid glands and their blood supply and also possibly to rapid uptake of calcium by the bones, which have been depleted of calcium by the thyrotoxicosis . Oral or intra- venous calcium supplementation suffices in most instances to control the symptoms. The calcium may be given slowly intravenously as calcium gluconate or calcium chloride in a dose ranging from 0.5 to 1.0 g every 4-8 hours, as indicated by clinical observation and determination of Ca2+. Replacement thyroid hormone- If sub-total throidectomy has been performed, thyroid hormeone replacement may not be needed. In 50-70% of patients, the residual gland is able to form enough hormone to prevent even transient clinical hypothyroidism. Serum hormone levels should be determined every two to four months until it is clear that the patient does not need replacement. Some surgeons give their patients thyroxine for an indefinite period after the operation in an attempt to avoid transient hypothyroidism and to remove any stimulus to regeneration of the gland. If total thyroidectomy has been performed, as is increasingly the case, full replacement doses of thyroxine (1.7 ug/kg BW, or about 1ug/pound of lean body mass) should be instituted immediately, and T4 levels checked in about 2 weeks for adjustment. Patients should be informed that they will need this treatment for life, and that they should re regularly checked, and consistent in their daily dosage. Long Term Follow-Up Probably the thyroid remnant is not normal. It has a rapid 131-I turnover rate and a small pool of stored organic iodine. Suppressibility by T3 administration returns within a few months of operation in some patients. TSAb tend to disappear from the blood in the ensuing 3 – 12 months [208-210]. After subtotal thyroidectomy, thyrotoxicosis recurs in 5 – 10% of patients, often many years after the original episode. The long term outcome of thyroid surgery for hyperthyroidism was reviewed by the Department of Surgery at Karolinska Institute. Of 380 patients observed and treated by surgery for thyrotoxicosis, primarily by subtotal thyroidectomy, 1% developed permanent hypoparathyroidism. Recurrent disease occurred in 2%. The operators intended to leave less than two grams of thyroid tissue, which presumably accounts for the low recurrence rate (210.1). Finally, adequate follow-up must be carried out after any kind of treatment of Graves’ disease. Recurrence is always possible, either early or late, and there is always the threat that the ophthalmopathic problems may worsen when all else in the progress of the patient seems favorable. A surprisingly large proportion of patients who have had subtotal thyroidectomy for Graves’ disease and who are clinically euthyroid can be shown to have an abnormal TRH response (excessive or depressed), and up to a third have elevated serum TSH levels [210, 211]. Some of them are undoubtedly mildly hypothyroid, whereas others are close to euthyroid but require the stimulation of TSH to maintain this state. These patients should have replacement T 4therapy if the elevated TSH persists. Over subsequent years the residual thyroid fails in more patients, due either to reduced blood supply, fibrosis from trauma, or continuing autoimmune thyroiditis. After 10 years, and depending on the extent of the original surgery, 20 – 40% are hypothyroid. This continuing thyroid failure is also seen after antithyroid drug therapy with 131-I and represents the natural evolution of Graves’ disease. SPECIAL CONSIDERATIONS IN THE TREATMENT OF THYROTOXICOSIS IN CHILDREN Thyrotoxicosis may occur in any age group but is unusual in the first five years of life. The same remarkable preponderance of the disease in females over males is observed in children as in the adult population, and the signs and symptoms of the disease are similar in most respects. Behavioral symptoms frequently predominate in children and produce difficulty in school or problems in relationships within the family. Thyrotoxic children are tall for their age, probably as an effect of the disease. These children are restored to a normal height/age ratio after successful therapy for the thyrotoxicosis. Permanent brain damage and craniosynostosis are reported as complications of early childhood thyrotoxicosis ( 211.1). Bone age is also often advanced . No more is known about the cause of the disease in children than in adults. Diagnosis rests upon eliciting a typical history and signs and upon the standard laboratory test results. Normal values for children are not the same as for adults during the first weeks of life, and these differencesshould be taken into account. Therapy of Childhood Graves’ Disease 131-I Treatment- In some clinics, RAI is used in the treatment of thyrotoxicosis in children. In one report, 73 children and adolescents were so treated. Hypothyroidism developed in 43. Subsequent growth and development were normal. In another group of 23 treated with 131-I, there were 4 recurrences, at least 5 became hypothyroid, and one was found to have a papillary thyroid cancer 20 months after the second dose . Safa et al. reviewed 87 children treated over 24 years and found no adverse effects except the well-known occurrence of hypothyroidism. Hamburger has examined therapy in 262 children ages 3 – 18 and concludes 131-I therapy to be the best initial treatment . Read et al (214.1) reviewed there experience with 131-I over a 36 year period, including six children under age 6, and 11 between 6 and 11 years. No adverse effects on the patients or their offsprings were found, and they advocate 131-I as a safe and effective treatment. Nevertheless, most physicians remain concerned about the risks of carcinogenesis, and the experience of Chernobyl has accentuated this concern. This problem was more fully discussed earlier in this chapter. Others believe that the risks of surgery and problems with antithyroid drug administration outweigh the potential risk of 131-I therapy. This problem was recently critically reviewed by Rivkees et al [214.1]. They point out the significant risks of reaction to antithyroid drugs, and of surgery. Surgery may have a mortality rate in hospital in children of about one per thousand operations, although this may have decreased in recent years. Among problems with radioactive iodide therapy, they note the whole body radiation, possibly worsening of eye disease, and the apparent lack of significant thyroid cancer risk so far reported among children treated with I-131 for Graves’ disease. They assumed that risk would be lower in children after age five, and especially after age ten, and if all thyroid cells were destroyed. They advise using higher doses of radioiodine to minimize residual thyroid tissue, and avoiding treatment of children under age five, but they believe that RAI is a convenient, effective, and useful therapy in children with Graves’ disease. However, as noted above, Rivkees own data indicate that treatnment of children with conventional doses of RAI may induce a lifetime risk of fatal cancer of over 2%, a very serious consideration (44.2) .Concern about the potential long term induction of cancer by RAI given to children is discussed above. Many physicians remain reluctant to use 131-I in children under age 15-18. Surgery- Although 131-I therapy may gain acceptance, the most common choice for therapy is between antithyroid drugs and subtotal thyroidectomy [213.1]. Proponents of antithyroid drug therapy believe that there is a greater tendency for remission of thyrotoxicosis in children compared to adults and that antithyroid drug therapy avoids the psychic and physical problems caused by surgery in this age group. With drugs the need for surgery (or 131-I) can be delayed almost indefinitely until conditions become favorable. As arguments against surgery, one must consider the morbidity and possible, although rare, mortality. Surgery means a permanent scar, and the recurrence rate is much higher (up to 15%) than that observed in adults. If the recurrence rate is kept acceptably low by performing near-total thyroidectomies, there is always an attendant rise in the incidence of permanent hypothyroidism, and greater potential for damage to the recurrent laryngeal nerves and parathyroid glands. Damage to the parathyroids necessitates a complicated medical program that may be permanent, and is one of the major reasons for opposing routine surgical therapy in this disease. However Rudberg et al reported that, in a series of 24 children treated surgically, only one had permanent hypoparathyroidism, and two recurred within 12 years. Soreide et al operated on 82 children and had no post-op nerve palsy, no tetany, nor mortality, and point out that surgery can provide a prompt, safe, and effective treatment. Childhood Graves’ disease was managed by near-total thyroidectomy in 78 patients of average age 13.8 years as reported by Sherman et al. Transient hypoparathyroidism and RCN damage were seen. Only three patients required subsequent 131-I treatment. Eighty-five % of those with ophthalmopathy were improved after surgery. The authors conclude that the treatment is safe and effective when performed by experienced surgeons (203.1).Others have pointed out the high relapse rate with all forms of therapy in the pediatric age group . The main argument favoring surgery is that it may correct the thyrotoxicosis with surety and speed, and result in less disruption of normal life and development than is associated with long-term administration of antithyroid drugs and the attendant constant medical supervision. Often children are unable to maintain the careful dosage schedule needed for control of the disease. If surgery is elected, the patient should be prepared with an antithyroid drug such as methimazole in a dosage and duration sufficient to produce a euthyroid state, and then should be given iodide for seven days before surgery. Lugol’s solution, or a saturated solution of potassium iodide, 1 or 2 drops twice daily, is sufficient to induce involution of the gland. Anti-thyroid drug therapy- Antithyroid drug therapy is the usual preferable initial therapy in children. Favorable indications for its use are mild thyrotoxicosis, a small goiter, recent onset of disease, and especially the presence of some obvious emotional problem that seems to be related to precipitation of the disease. Antithyroid drug administration necessitates much supervision by the physician and the parents, the permanent remission rate will be 50% or less , and there is always the possibility of a reaction to the medication. There is no consensus on secondary treatment if antithyroid drugs fail.. Some physicians favor surgery if the patient and parents seem incapable of following a regimen requiring frequent administration of medicine for a prolonged period or drug reactions occur. A factor that must be remembered in selecting the appropriate course of therapy is the experience of the available surgeon. Lack of experience contributes to a high rate of recurrence, permanent hypothyroidism, or permanent hypoparathyroidism. Other physicians believe the possible but unproven risks of 131-I are more than outweighed by the known risks of operation, and 131-I treatment is increasingly accepted for patients over age 15. If antithyroid drugs are chosen as primary therapy, the patient is initially given a course of treatment for one or two years, according to the dosage schedule shown in Table 11-9. The dosage of PTU (if used) needed is usually 120 – 175 mg/m2 body surface area daily divided into three equal doses every eight hours. Methimazole can be used in place of PTU; approximately one-tenth as much, in milligrams, is required. Methimazole is now the preferred drug. During therapy the dosage can usually be gradually reduced. Many patients will be satisfactorily controlled by once-a-day treatment. Although the plasma half-life of methimazole in children is only 3-6 hours, the drug is concentrated in the thyroid and maintains higher levels there for up to 24 hours after a dose [215.1]. The program is similar to that employed in adult thyrotoxicosis. It is sensible to see the child once each month, and at that time to make sure that the program is being followed and progress made. Any evidence of depression of the bone marrow should prompt a change to an alternative drug or a different form of treatment, as discussed below. At the end of one or two years the medication is withdrawn. If thyrotoxicosis recurs, a second course of treatment lasting for one year or more may be given. A decrease in the size of the goiter during therapy is good evidence that a remission has been achieved. Progressive enlargement of the gland during therapy implies that hypothyroidism has been produced. This enlargement can be controlled by reduction in the dose of antithyroid drug or by administration of replacement thyroid hormone. There is no adequate rule for deciding when medical therapy has failed. After courses of antithyroid drug therapy totaling two to four years and attainment of age 15, if the patient still has not entered a permanent remission it is probably best to proceed with surgical or 131-I treatment. Barrio et al (215.1) reported on truly long term antithyroid drug therapy, which achieved 40% remissions in pediatric patients, with average time to remission of 5.4 years. Non-remitters were cured by RAI or surgery. Leger reported a similar program with 50% of children appearing to enter a permanent remission (215.12). Occasionally a drug reaction develops while the condition is being controlled with an antithyroid drug. A change to another thiocarbamide may be satisfactory, but patients should be followed carefully. If a reaction is seen again, or if severe neutropenia occurs, it is usually best to stop antithyroid drug therapy and (1) give potassium iodide and an agent such as propranolol and to proceed with surgery, or (2) to give 131-I. RAI therapy will be necessary if surgery is contraindicated by uncontrollable thyrotoxicosis,for whatever reason, or with prior thyroidectomy. Thyrotoxicosis in children has been recently reviewed(215.2) Approximate daily dose of MMI (mg) Intrauterine and Neonatal Thyrotoxicosis Thyrotoxicosis in utero is a rare but recognized syndrome occurring in pregnant women with very high TSH-R stimulating Ab in serum, due to transplacental passage of antibodies. It can also develop in the neonate. It is possible to screen for this risk by assaying TSAb in serum of pregnant women with known current or prior Graves’ Disease. Intra-uterine thyrotoxicosis causes fetal tachycardia, failure to grow, acceleration of bone age, premature closure of sutures, and occasionally fetal death. Multiple sequential pregnancies with this problem have been recorded. Clinical diagnosis is obviously inexact. Antithyroid drugs can be given, but control of the dosage is uncertain . Propylthiouracil is considered to be the safest drug to use in the first trimester, because of fetal anomalies attributed to methimazole exposure in early pregnancy( 217.1), with switching to MMI in the second and third trimesters.. Luton et al (217.1) recently provided their extensive experience in managing these difficult cases. Measurement of TSAb is important. Mothers with negative TSAb assay, and not on ATD, rarely have any fetal problem. Mothers with positive TSAb or on ATD must be monitored by following maternal hormone and TSH levels, fetal growth , heart rate, and by ultrasound for evidence of goiter or other signs of fetal hyper- or hypothyroidism. If maternal hormone levels are low and TSH elevated, with fetal goiter and evidence of hypothyroidism, ATD therapy is reduced and intra-amniotic T4 may be given. If maternal T4 levels high and TSH low, with fetal goiter and signs of fetal hyperthyroidism, increased doses of ATD are suggested. If the probable metabolic status of the fetus is not clear, fetal blood sampling is feasible although carrying significant risk to the fetus. Plasmapheresis to reduce maternal TRAb has been recommended, but few facts are available. Thyrotoxicosis is rare in the newborn infant and is usually associated with past or present maternal hyperthyroidism. Neonatal hypermetabolism usually arises from transplacental passage of TSAb. Frequently the infant is not recognized as thyrotoxic at birth, but develops symptoms of restlessness, tachycardia, poor feeding, occasionally excessive hunger, excessive weight loss, and possibly fever and diarrhea a few days after birth. The fetus converts T4 to T3 poorly in utero, but switches to normal T4 to T3 deiodination at birth. This phenomenon may normally provide a measure of protection in utero that is lost at birth, allowing the development of thyrotoxicosis in a few days. The syndrome may persist for two to five weeks, until the effects of the maternal antibodies have disappeared. The patient may be treated with propranolol, antithyroid drugs given according to the schedule above, and iodide. The antithyroid drug can be given parenterally if necessary in saline solution after sterilization by filtration through a Millipore filter. Newborn infants with thyrotoxicosis are frequently extremely ill, and ancillary therapy, including sedation, cooling, fluids in large amounts, electrolyte replacement, and oxygen, are probably as important in management as specific therapy for the thyrotoxicosis. Propranolol is used to control the tachycardia (218.1). Because of the increased metabolism of such infants, attention to fluid balance and adequacy of nutrition are important. The patient usually survives the thyrotoxicosis, and the disease is typically self-limiting, with the euthyroid state being established in one or two months. Antithyroid medication can be gradually withdrawn at this time. Graves’ disease can also occur in the newborn because the same disturbance that is causing the disorder in the mother is also occurring independently in the child. Hollingsworth et al have described their experience in such patients. The mothers did not necessarily have active disease during pregnancy. Graves’ disease persisted in these patients from birth far beyond the time during which TSAb of maternal origin could persist. Advanced bone age was one feature of the disorder. Behavioral disturbances were later found in some of these children at a time when they were euthyroid. General Therapeutic Relationship of the Patient and Physician The foregoing discussion explains several methods for specifically decreasing thyroid hormone formation. They are, in a sense, both unphysiologic and traumatic to the patient. As a good physician realizes in any problem, but especially in Graves’ disease, attention to the whole patient is mandatory. During the initial and subsequent interviews, the physician caring for a patient with Graves’ disease should recognize any psychological and physical stresses. Frequently major emotional problems come to light after the patient recognizes the sincere interest of the physician. Typically the problem involves interpersonal relationships and often is one of matrimonial friction. The upset may be deep-seated and may involve very difficult adjustments by the patient, but characteristically it is related to identifiable factors in the environment. To put it another way, the problem is not an endogenous emotional reaction but a difficult adjustment to real external problems. On the other hand, one must be aware that the emotional lability of the thyrotoxic patient may be a trial for those with whom he or she must live, as well as for the patient. Thus thyrotoxicosis itself may create interpersonal problems. From whatever cause they arise, these problems are dealt with insofar as possible by the wise physician. We have been unimpressed by the benefits of formal psychiatric care for the average thyrotoxic patient, but are certain that sympathetic discussion by the physician, possibly together with assistance in environmental manipulation, is an important part of the general attack on Graves’ disease. In other cases, personal problems may play a less important etiologic role but may still strongly affect therapy by interfering with rest or by causing economic hardship. In addition to providing assistance in solving personal problems, two other general therapeutic measures are important. The first is rest. The patient with Graves’ disease should have time away from normal duties to help in reestablishing his or her psychic and physiologic equilibria. Patients can and do recover with appropriate therapy while continuing to work, but more rapid and certain progress is made if a period away from the usual occupation can be provided. Often a mild sedative or tranquilizer is helpful. Another important general measure is attention to nutrition. Patients with Graves’ disease are nutritionally depleted in proportion to the duration and severity of their illness. Until metabolism is restored to normal, and for some time afterward, the caloric and protein requirements of the patient may be well above normal. Specific vitamin deficiences may exist, and multivitamin supplementation is indicated. The intake of calcium should be above normal. Diagnosis of the classic form of Graves’ disease is easy and depends on the recognition of the cardinal features of the disease and confirmation by such tests as TSH and FTI. The differential diagnosis includes other types of thyrotoxicosis, such as that occurring in a nodular gland, accompanying certain tumors of the thyroid, or thyrotoxicosis factitia, and nontoxic goiter in a patient with symptoms that imitate those of thyrotoxicosis. Types of hypermetabolism not of thyroid origin must also enter the differential diagnosis. Examples are certain cases of pheochromocytoma, polycythemia, lymphoma, and the leukemias. Pulmonary disease, infection, parkinsonism, pregnancy, or nephritis may stimulate certain features of thyrotoxicosis. Treatment of Graves’ disease cannot yet be aimed at the cause because it is still unknown. One seeks to control thyrotoxicosis when that seems to be the major indication, or the ophthalmopathy when that aspect of the disease appears to be more urgent. The available forms of treatment, including surgery, drugs, and 131-I therapy, are reviewed. There is a difference of opinion as to which of these modalities is best, but to a large degree guidelines governing choice of therapy can be drawn. Antithyroid drugs are widely used for treatment on a long- term basis. About one-third of the patients undergoing long-term antithyroid therapy achieve permanent euthyroidism. Drugs are the preferred initial therapy in children and young adults. Subtotal thyroidectomy is a satisfactory form of therapy, if an excellent surgeon is available, but is used infrequently by many thyroidologists. The combined use of antithyroid drugs and iodine makes it possible to prepare patients adequately before surgery, and operative mortality is approaching the vanishing point. Many young adults, especially males, are treated by surgery if antithyroid drug treatment fails. Currently, most endocrinologists consider RAI to be the best treatment for adults, and consider the associated hypothyroidism to be a minor problem. Evidence to date after well over five decades of experience indicates that the risk of late thyroid carcinoma must be near zero. The authors advise this therapy in most patients over age 40, and believe that it is not contraindicated above the age of about 15. Dosage is calculated on the basis of 131-I uptake and gland size. Most patients are cured by one treatment. The principal side effect is the occurrence of hypothyroidism. This complication occurs with a fairly constant frequency for many years after therapy and may be an inevitable complication in many patients if cure of the disease is to be achieved. Many therapists accept this as an anticipated outcome of treatment. Thyrotoxicosis in children is best handled initially by antithyroid drug therapy. If this therapy does not result in a cure, surgery may be performed. Treatment with 131-I is accepted as an alternative form of treatment by some physicians. Neonatal thyrotoxicosis is a rarity. Antithyroid drugs, propranolol and iodide may be required for several weeks until maternally-derived antibodies have been metabolized. The physician applying any of these forms of therapy to the control of thyrotoxicosis should also pay heed to the patient’s emotional needs, as well as to his or her requirements for rest, nutrition, and specific antithyroid medication. 1. Wayne EJ: The diagnosis of thyrotoxicosis. 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Kulkarni RS, Braverman LE, Patwardhan NA. Bilateral cervical plexus block for thyroidectomy and parathyroidectomy in healthy and high risk patients. J Endocrinol Invest 19:714-718, 1996. 192.2. Schwartz AE, Clark OH, Ituarte P, Gerfo PL. Thyroid surgery â€“ the choice. J Clin Endocrinol Metab 83:1097-1105, 1998. 193. Bewsher BD, Pegg CAS, Stewart DJ, Lister DA, Michie W: Propranolol in the surgical management of thyrotoxicosis. Ann Surg 180:787, 1974. 194. Toft AD, Irvine WJ, Campbell RWF: Assessment by continuous cardiac monitoring of minimum duration of preoperative propranolol treatment in thyrotoxic patients. Clin Endocrinol 5:195, 1976. 195. Toft AD, Irvine WJ, Sinclair I, McIntosh D, Seth J, Cameron EHD: Thyroid function after surgical treatment of thyrotoxicosis. N Engl J Med 298:643, 1978. 195a. Bogazzi F, Miccoli P, Berti P, Cosci C, Brogioni S, Aghini-Lombardi F, Materazzi G, Bartalena L, Pinchera A, Braverman LE, Martino E. 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[Epub ahead of print Total Thyroidectomy Is Superior to Subtotal Thyroidectomy for Management of Graves’ Disease in the United States. 197. Colcock BP, King ML: The mortality and morbidity of thyroid surgery. Surg Gynecol Obstet 114:131, 1962. 198. Sawyers JL, Martin CE, Byrd BF Jr, Rosenfield L: Thyroidectomy for hyperthyroidism. Ann Surg 175:939, 1972. 199. Farnell MB, van Heerden JA, McConahey WM, Carpenter HA, Wolff LH Jr: Hypothyroidism after thyroidectomy for Graves’ disease. Amer J Surg 142:535, 1981. 200. Klementschitsch P, Shen K-L, Kaplan EL: Reemergence of thyroidectomy as treatment for Graves’ disease. Surg Clin North Am 59:35, 1979. 200a. Palit TK, Miller CC, Miltenburg DM. The efficacy of thyroidectomy for Graves’ disease: A meta-analysis. J Surg Res 90:161-165, 2000. 201. Winsa B, Rastad J, Akerstrom G, Johansson H, Westermark K, Karlsson FA. Retrospective evaluation of the effect of subtotal and total thyroidectomy in the treatment of Graves’ disease with and without endocrine ophthalmopathy. Thesis, Brita Winsa, The University of Upsala, Upsala, Sweden, 1993. 201a. Stocker DJ, Foster SS, Solomon BL, Shriver CD, Burch HB. Thyroid cancer yield in patients with Gravesâ€™ disease selected for surgery on the basis of cold scintiscan defects. Thyroid 12:305, 2002. 201b-( Träisk F, Tallstedt L, Abraham-Nordling M, Andersson T, Berg G, Calissendorff J, Hallengren B, Hedner P, Lantz M, Nyström E, Ponjavic V, Taube A, Törring O, Wallin G, Asman P, Lundell G; Thyroid Study Group of TT 96. J Clin Endocrinol Metab. 2009 Oct;94(10):3700-7. 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Clin Endocrinol 7:367, 1977. 202a: Scholz GH, Hagemann E, Arkenau C, Engelmann L, Lamesch P, Schreiter D,Schoenfelder M, Olthoff D, Paschke R. Is there a place for thyroidectomy in older patients with thyrotoxic storm and cardiorespiratory failure?Thyroid. 2003 Oct;13(10):933-40. 203. Soreide JA, van Heerden JA, Lo CY, Grant CS, Zimmerman D, Ilstrup DM. Surgical treatment of Gravesâ€™ disease in patients younger than 18 years. World J Surg 20:794-800, 1996. 203.1 Sherman J, Thompson GB, Lteif A, Schwenk WF 2nd, van Heerden J, Farley DR, Kumar S, Zimmerman D, Churchward M, Grant CS.Surgical management of Graves disease in childhood and adolescence: an institutional experience.Surgery. 2006 Dec;140(6):1056-61 204. Miccoli P, Vitti P, Rago T, Iacconi P, Bartalena L, Bogazzi F, Fiore E, Valeriano R, Chiovato L, Rocchi R, Pinchera A. Surgical treatment of Gravesâ€™ disease: Subtotal or total thyroidectomy? Surgery 120:1020-1025, 1996. 204.a Torring O, Tallstedt L, Wallin G, Lundell G, Ljunggren J-G, Taube A, Saaf M, Hamberger B, and The Thyroid Study Group. Graves’ hyperthyroidism: Treatment with antithyroid drugs, surgery, or radioiodine-a prospective, randomized study. J Clin Endocrinol Metab 81:2986-2993, 1996. 204b. Moleti M 204b. Moleti M, Mattina F, Lo Presti VP, Baldari CS, Bonanno N, Trimarchi F, Vermiglio F. Role of residual thyroid tissue ablation after thyroidectomy for Graves’ disease. Its effects on the course of related ophthalmopathy. J Endocrinol Invest 23:37, 2000. 204c. De Bellis A 204c. De Bellis A, Bizzarro A, Perrino S, Coronclla C, Iorio S, Pepe M, Guaglione M, Wall JR, Bellastella A. Improvement of severe ophthalmopathy and decrease of antibodies against extraocular muscles, G2s, and Fp subunit of succinate dehydrogenase after near-total thyroidectomy in Graves’ disease. J Endocrinol Invest 23:14, 2000. 204d. Marcocci C 204d. Marcocci C, Bruno-Bossio G, Manetti L, Tanda ML, Miccoli P, Iacconi P, Bartolomei MP, Nardi M, Pinchera A, Bartalena L. The course of Graves’ ophthalmopathy is not influenced by near-total thyroidectomy; a case-control study. Clin Endocrinol 51:503-508, 1999. 204e. Moleti, M; Mattina, F; Salamone, I; Violi, MA; Nucera C; Baldari, S; Schiavo, MGL; Regalbuto, C; Trimarchi, F; Vermiglio, F. Effects of thyroidectomy alone or followed by radioiodine ablation of thyroid remnants on the outcome of Gravesâ€™ ophthalmopathy. Thyroid 13 653-658 2003. 204f: Panzer C, Beazley R, Braverman L. Rapid preoperative preparation for severe hyperthyroid Graves’ disease.JClin Endocrinol Metab. 2004 May;89(5):2142-4. 204g. Menconi F, Marinò M, Pinchera A, Rocchi R, Mazzi B, Nardi M, Bartalena L, Marcocci C.Effects of total thyroid ablation versus near-total thyroidectomy alone on mild to moderate Graves’ orbitopathy treated with intravenous glucocorticoids. J Clin Endocrinol Metab. 2007 May;92(5):1653-8.IN 205. Yamashita H, Noguchi S, Tahara K, Watanabe S, Uchino S, Kawamoto H, Toda M, Murakami N. Postoperative tetany in patients with Gravesâ€™ disease: A risk factor analysis. Clin Endocrinol 47:71-77, 1997. 206. Buchanan WW, Koutras DA, Crooks J, Alexander WD, Brass W, Anderson JR, Goudie RB, Gray KG: The clinical significance of the complement-fixation test in thyrotoxicosis. J Endocrinol 24:115, 1962. 207. Michie W, Duncan T, Hamer-Hodges DW, Bewsher PD, Stowers JM, Pegg CAS, Hems G, Hedley AJ: Mechanism of hypocalcemia after thyroidectomy for thyrotoxicosis. Lancet 1:508, 1971. 208. Hardisty CA, Talbot CH, Munro DS: The effect of partial thyroidectomy for Graves’ disease on serum long-acting thyroid stimulator protector (LATS-P). Clin Endocrinol 14:181, 1981. 209. Bech K, Feldt-Rasmussen U, Bliddal H, Date J, Blichert-Toft M: The acute changes in thyroid stimulating immunoglobulins, thyroglobulin, and thyroglobulin antibodies following subtotal thyroidectomy. Clin Endocrinol 16:235, 1982. 210. Fukino O, Tamai H, Fujii S, Ohsako N, Matsubayashi S, Kuma K, Nagataki S: A study of thyroid function after subtotal thyroidectomy for Graves’ disease: particularly on TRH tests, T3 suppression tests and antithyroid antibodies in euthyroid patients. Acta Endocrinol 103:28-33, 1983. 210.1. Werga-Kjellman P, Zedenius J, Tallstedt L, Traisk F, Lundell G, Wallin G. Surgical treatment of hyperthyroidism: A ten year experience. Thyroid 11:187-192, 2001. 211. Hedley AJ, Hall R, Amos J, Michie W, Crooks J: Serum-thyrotropin levels after subtotal thyroidectomy for Graves’ disease. Lancet 1:455, 1971. 211.1 Segni M, Leonardi E, Mazzoncini B, Pucarelli I, Pasquino AM. 1999 Special features of Graves’ disease in early childhood. Thyroid 9:871. 212. Hung W, Wilkins L, Blizzard R: Medical therapy of thyro- toxicosis in children. Pediatrics 30:17, 1962. 213. Starr P, Jaffe HL, Oettinger L Jr: Late results of 131-I treatment of hyperthyroidism in seventy-three children and adosescents. J Nucl Med 5:81, 1964. 213.1. Perrild H, Jacobsen BB. Thyrotoxicosis in childhood. Europ J Endocrinol 134:678-679, 1996. 214. Kogut MD, Kaplan SA, Collipp PJ, Tiamsic T, Boyle D: Treatment of hyperthyroidism in children. N Engl J Med 272:217, 1965. 214.1. Rivkees SA, Sklar C, Freemark M. The management of Gravesâ€™ disease in children, with special emphasis on radioiodine treatment. J Clin Endocrinol Metab 83:3767-3776. 214.11: Read CH Jr, Tansey MJ, Menda Y. A 36-year retrospective analysis of the efficacy and safety of radioactive iodine in treating young Graves’ patients. J Clin Endocrinol Metab. 2004 Sep;89(9):4229-33. 215.1. Okuno A, Yano K, Inyaku F, Suzuki Y, Sanae N, Kumai M, Naitoh Y. Pharmacokinetics of methimazole in children and adolescents with Gravesâ€™ disease. Acta Endocrinol (Copenh) 115:112-118, 1987. 215.1 Barrio R, Lopez-Capape M, Martinez-Badas I, Carrillo A, Moreno JC, Alonso M.Graves’ disease in children and adolescents: response to long-term treatment.Acta Paediatr. 2005 Nov;94(11):1583-9 215.12 Léger J, Gelwane G, Kaguelidou F, Benmerad M, Alberti C; French Childhood Graves’ Disease Study Group Positive impact of long-term antithyroid drug treatment on the outcome of children with Graves’ disease: national long-term cohort study.J Clin Endocrinol Metab. 2012 Jan;97(1):110-9. 215.2 Koch CA, Sarlis NJ. The spectrum of thyroid diseases in childhood and its evolution during transition to adulthood: Natural history, diagnosis, differential diagnosis and management. J Endocrinol Invest 24:659-675, 2001. 216. Rudberg C, Johansson H, Akerstrom G, Tuvemo T, Karlsson FA. Gravesâ€™ disease in children and adolescents. Late results of surgical treatment. Europ J Endocrinol 134:710-715, 1996. 217.1 Clementi M, Di Gianantonio E, Pelo E, Mammi I, Basile RT, Tenconi R. 1999 Methimazole embryopathy: delineation of the phenotype. Amer J Medical Genet. 83:43-46. 217. Cheek JH, Rezvani I, Goodner D, Hopper B: Prenatal treatment of thyrotoxicosis to prevent intrauterine growth retardation. Obstet Gynecol 60:122, 1982. 217.1 Luton D, Le Gac I, Vuillard E, Castanet M, Guibourdenche J, Noel M, Toubert ME, Leger J, Boissinot C, Schlageter MH, Garel C, Tebeka B, Oury JF, Czernichow P, Polak M.Management of Graves’ disease during pregnancy: the key role of fetal thyroid gland monitoring.J Clin Endocrinol Metab. 2005 Nov;90(11):6093-8 218.1 Zimmerman D. 1999 Fetal and neonatal hyperthyroidism. Thyroid 9:727. 218. Jarett SN, Seniour B, Braudo JL, Heymann S: Neonatal thyrotoxicosis. Pediatrics 24:65, 1959. 219. Hollingsworth DR, Mabry CC, Eckerd JM: Hereditary aspects of Graves’ disease in infancy and childhood. 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Autism Spectrum Disorder is a general umbrella term for a neurodevelopmental condition with deficits in social interaction and communication, stereotyped or repetitive behaviors and interests, sensory issues, and in some cases, cognitive delays. IT is called an “umbrella” because it encompasses some of the neurodevelopmental disorders with the same symptoms in a continuum. They are as follows (from severe to mild): - Rett’s Syndrome - Autistic Disorder - Childhood Disintegrative Disorder - Pervasive Developmental Disorder – Not Otherwise Specified (PDD-NOS) - Atypical Autism - Asperger’s Syndrome The “common” autism that most of us know is the Autistic disorder, where the child who has it has all the classic symptoms of autism and is non-verbal. But there are also “milder” versions or milder disorders similar to the autistic disorder like Asperger’s syndrome and a genetic disorder similar also to autism like Rett’s syndrome (for my general article in autism, click here). However, due to the overlapping symptoms and misuse of these disorders led the American Psychiatric Association revised their Diagnostic and Statistical Manual of Mental Disorders (DSM) and remove these autism-related disorders and instead absorbed them into the umbrella term “autism spectrum disorder.” However, the World Health Organization’s disease manual, International Classification of Diseases (ICD), did not remove these disorders, but placed them under the general category of “Pervasive Developmental Disorders.” DSM-IV (the fourth edition) has this list of autism and its related disorders: - 299.00 Autistic Disorder - 299.80 Rett’s Disorder - 299.10 Childhood Disintegrative Disorder - 299.80 Asperger’s Disorder - 299.80 Pervasive Developmental Disorder NOS (not otherwise specified) F84 Pervasive developmental disorders - F84.0 Childhood autism - F84.1 Atypical autism - .10 Atypicality in age of onset - .11 Atypicality in symptomatology - .12 Atypicality in both age of onset and symptomatology - F84.2 Rett’s syndrome - F84.3 Other childhood disintegrative disorder F84.4 Overactive disorder associated with mental retardation and stereotyped movements - F84.5 Asperger’s syndrome - F84.8 Other pervasive developmental disorders - F84.9 Pervasive developmental disorder, unspecified Whereas, the DSM-5 has now its criteria for autism spectrum disorders, according to severity: Autism Spectrum Disorder 299.00 (F84.0) A. Persistent deficits in social communication and social interaction across multiple contexts, as manifested by the following, currently or by history (examples are illustrative, not exhaustive, see text): 1. Deficits in social-emotional reciprocity, ranging, for example, from abnormal social approach and failure of normal back-and-forth conversation; to reduced sharing of interests, emotions, or affect; to failure to initiate or respond to social interactions. 2. Deficits in nonverbal communicative behaviors used for social interaction, ranging, for example, from poorly integrated verbal and nonverbal communication; to abnormalities in eye contact and body language or deficits in understanding and use of gestures; to a total lack of facial expressions and nonverbal communication. 3. Deficits in developing, maintaining, and understanding relationships, ranging, for example, from difficulties adjusting behavior to suit various social contexts; to difficulties in sharing imaginative play or in making friends; to absence of interest in peers. Specify current severity: Severity is based on social communication impairments and restricted repetitive patterns of behavior (see Table 2). B. Restricted, repetitive patterns of behavior, interests, or activities, as manifested by at least two of the following, currently or by history (examples are illustrative, not exhaustive; see text): 1. Stereotyped or repetitive motor movements, use of objects, or speech (e.g., simple motor stereotypies, lining up toys or flipping objects, echolalia, idiosyncratic phrases). 2. Insistence on sameness, inflexible adherence to routines, or ritualized patterns or verbal nonverbal behavior (e.g., extreme distress at small changes, difficulties with transitions, rigid thinking patterns, greeting rituals, need to take same route or eat food every day). 3. Highly restricted, fixated interests that are abnormal in intensity or focus (e.g, strong attachment to or preoccupation with unusual objects, excessively circumscribed or perseverative interest). 4. Hyper- or hyporeactivity to sensory input or unusual interests in sensory aspects of the environment (e.g., apparent indifference to pain/temperature, adverse response to specific sounds or textures, excessive smelling or touching of objects, visual fascination with lights or movement). Specify current severity: Severity is based on social communication impairments and restricted, repetitive patterns of behavior (see Table 2). C. Symptoms must be present in the early developmental period (but may not become fully manifest until social demands exceed limited capacities, or may be masked by learned strategies in later life). D. Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning. E. These disturbances are not better explained by intellectual disability (intellectual developmental disorder) or global developmental delay. Intellectual disability and autism spectrum disorder frequently co-occur; to make comorbid diagnoses of autism spectrum disorder and intellectual disability, social communication should be below that expected for general developmental level. Note: Individuals with a well-established DSM-IV diagnosis of autistic disorder, Asperger’s disorder, or pervasive developmental disorder not otherwise specified should be given the diagnosis of autism spectrum disorder. Individuals who have marked deficits in social communication, but whose symptoms do not otherwise meet criteria for autism spectrum disorder, should be evaluated for social (pragmatic) communication disorder.Specify if: With or without accompanying intellectual impairment With or without accompanying language impairment Associated with a known medical or genetic condition or environmental factor (Coding note: Use additional code to identify the associated medical or genetic condition.) Associated with another neurodevelopmental, mental, or behavioral disorder (Coding note: Use additional code[s] to identify the associated neurodevelopmental, mental, or behavioral disorder[s].) With catatonia (refer to the criteria for catatonia associated with another mental disorder, pp. 119-120, for definition) (Coding note: Use additional code 293.89 [F06.1] catatonia associated with autism spectrum disorder to indicate the presence of the comorbid catatonia.) Table 2 Severity levels for autism spectrum disorder Severity level Social communication Restricted, repetitive behaviors Level 3 “Requiring very substantial support” Severe deficits in verbal and nonverbal social communication skills cause severe impairments in functioning, very limited initiation of social interactions, and minimal response to social overtures from others. For example, a person with few words of intelligible speech who rarely initiates interaction and, when he or she does, makes unusual approaches to meet needs only and responds to only very direct social approaches Inflexibility of behavior, extreme difficulty coping with change, or other restricted/repetitive behaviors markedly interfere with functioning in all spheres. Great distress/difficulty changing focus or action. Level 2 “Requiring substantial support” Marked deficits in verbal and nonverbal social communication skills; social impairments apparent even with supports in place; limited initiation of social interactions; and reduced or abnormal responses to social overtures from others. For example, a person who speaks simple sentences, whose interaction is limited to narrow special interests, and how has markedly odd nonverbal communication. Inflexibility of behavior, difficulty coping with change, or other restricted/repetitive behaviors appear frequently enough to be obvious to the casual observer and interfere with functioning in a variety of contexts. Distress and/or difficulty changing focus or action. Level 1 Without supports in place, deficits in social communication cause noticeable impairments. Difficulty initiating social interactions, and clear examples of atypical or unsuccessful response to social overtures of others. May appear to have decreased interest in social interactions. For example, a person who is able to speak in full sentences and engages in communication but whose to- and-fro conversation with others fails, and whose attempts to make friends are odd and typically unsuccessful. Inflexibility of behavior causes significant interference with functioning in one or more contexts. Difficulty switching between activities. Problems of organization and planning hamper independence Hmmm… But what’s the implication of removing milder forms of autism in the DSM-5? The separate diagnoses of autistic disorder, PDD-NOS, and Asperger syndrome is no longer applicable. Meaning, only the autism spectrum disorder (ASD) is applied regardless of severity. ASD is the new single diagnosis of all forms of autism. The DSM also removed Rett’s syndrome because it is a genetic/chromosomal disorder and is similar to other chromosomal disorders like fragile X syndrome, tuberous sclerosis, or Down syndrome and it has a known molecular etiology. However, there will be a conflict when the DSM is compared to the ICD, where Rett’s syndrome is still under pervasive developmental disorders, and Asperger’s syndrome is not yet removed. Overlapping diagnoses of ASD or PDD will be still common. Another problem that DSM-5 changes may bring is the acceptance among people with milder forms of autism. Since disorders like Asperger’s and PDD-NOS are eliminated, they are now confused with autistic disorder; some people even protested against the DSM’s changes. Patients and parents alike became anxious about these change. This anxiety ranges from a mild concern on the part of some parents to angry protest: More than 8,000 people signed an online petition circulated by the Global and Regional Asperger’s Syndrome Partnership; another petition sponsored by Asperger’s Association of New England received 5,400 signatures. But why is the DSM-5 has changed criteria for diagnosing ASD (if it causes confusion and anxiety to the autism community)? Experts from APA have this explanation about DSM-5 changes in a Slate magazine article: The logic behind the changes seems sound. “There wasn’t any evidence after 17 years that [the DSM-IV diagnoses] reflected reality,” says Bryan King, director of Seattle Children’s Autism Center, who served on the APA task force charged with revamping the diagnosis. “There was no consistency in the way Asperger’s or PDD-NOS was applied.” In fact, a 2011 study by Catherine Lord (another member of the task force) and more than 35 colleagues reported, “In these 12 university-based sites, with research clinicians selected for their expertise in ASD and trained in using standardized instruments, there was great variation in how best-estimate clinical diagnoses within the autism spectrum (i.e., autistic disorder, PDD-NOS, Asperger’s disorder) were assigned to individual children.” This argument sounds right, but some experts don’t agree because milder forms of autism has more subtle symptoms than the autistic disorder, and most countries don’t even recognize milder autism forms because people with these conditions can be verbal and independent (but still with social and communication deficits). Another quote from Slate: Certain states provide services for children diagnosed with autism but not for those diagnosed with Asperger’s. “It was difficult to get kids with Asperger’s services because their deficits can be subtle, so they were left on their own to some degree,” says Matthew Siegel, director of the Developmental Disorders Program at Spring Harbor Hospital in Maine. And it’s not just those with Asperger’s who have been shortchanged by the current system, says Stewart Newman, who treats kids from all parts of the spectrum at Mind Matters PC in Oregon. He has spent many hours advocating for his patients with educators who had “a lack of clarity about what the diagnosis of PDD-NOS in particular meant, and how the children should be characterized for special services.” Parents of children with autistic disorder are now worried about integrating higher functioning children with the low functioning ones; hence, blurring of the distinction of the severe and milder form of autism spectrum disorders. Parents of lower-functioning kids are also concerned about how the influx of high-functioning individuals will affect the public’s perception of autism—mainly because they feel autism is a serious disorder that people should associate with profound disability. One mother commented online that “the proposed DSM change would diminish the enormity of the challenges that those with moderate to severe autism have.” Ursitti, who has a daughter with Asperger’s and a son with severe autism, feels this is already happening: “If we have this national perspective that autism is a blessing, that it’s not a crisis, the ones who will lose out are the expensive ones, the severe ones. Legislators focus on the cheapest option, and celebration is cheaper than treatment.” That parent’s comment is right, this change may lessen the severity of autism symptoms and may forget the classic autism and will only recognize milder forms of autism. Not good. But somehow, the DSM has its autism spectrum severity scale from 1 (mild) to 3 (severe). What is my opinion about the DSM-5 change? I really do not know my standing about the changes in the DSM-5. But I find the ICD-10 more accurate than the DSM-5. I wish APA never eliminated autism-related disorders and integrated them into the umbrella of ASD, though I slightly agree with their elimination of Rett’s syndrome because it is chromosomal, but it has still autism-like symptoms. But with the removal of autism-related disorders, laymen will never know milder forms of autism (particularly in my native Philippines) and also the public will never know the internal struggles of people with milder autism and other pervasive developmental disorders and may only trivialize people with autism as either mutes or eccentric geeks, without seeing - Abbeduto, Leonard; Ozonoff, Susan; Thurman, Angela John; McDuffie, Angela; Schweitzer, Julie. Hales, Robert; Yudofsky, Stuart; Robert, Laura Weiss, eds. Chapter 8. Neurodevelopmental Disorders, The American Psychiatric Publishing Textbook of Psychiatry (6 ed.). Arlington, VA: American Psychiatric Publishing. ISBN 978-1-58562-444-7. Retrieved 11 March 2015.	2	8	1	0	0	3	0.704567	4	3,139
- Brain ischemia Brain ischemia Classification and external resources CT scan slice of the brain showing a right-hemispheric cerebral infarct (left side of image). ICD-10 G45.9, I67.8 ICD-9 435X,437X MeSH D002545 Brain ischemia, also known as cerebral ischemia, is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and thus to the death of brain tissue or cerebral infarction / ischemic stroke. It is a sub-type of stroke along with subarachnoid hemorrhage and intracerebral hemorrhage. Ischemia leads to alterations in brain metabolism, reduction in metabolic rates, and energy crisis. There are two types of ischemia: focal ischemia, which is confined to a specific region of the brain; and global ischemia, which encompasses wide areas of brain tissue. The main symptoms involve impairments in vision, body movement, and speaking. The causes of brain ischemia vary from sickle cell anemia to congenital heart defects. Symptoms of brain ischemia can include unconsciousness, blindness, problems with coordination, and weakness in the body. Other effects that may result from brain ischemia are stroke, cardiorespiratory arrest, and irreversible brain damage. An interruption of blood flow to the brain for more than 10 seconds causes unconsciousness, and an interruption in flow for more than a few minutes generally results in irreversible brain damage. In 1974, Hossmann and Zimmerman demonstrated that ischemia induced in mammalian brains for up to an hour can be at least partially recovered. Accordingly, this discovery raised the possibility of intervening after brain ischemia before the damage becomes irreversible. The broad term, "stroke" can be divided into three categories: brain ischemia, subarachnoid hemorrhage and intracerebral hemorrhage. Brain ischemia can be further subdivided, by cause, into thrombotic, embolic, and hypoperfusion. Thrombotic and embolic are generally focal or multifocal in nature while hypoperfusion affects the brain globally. Focal brain ischemia Focal brain ischemia occurs when a blood clot has occluded a cerebral vessel. Focal brain ischemia reduces blood flow to a specific brain region, increasing the risk of cell death to that particular area. It can be either caused by thrombosis or embolism. Global brain ischemia Global brain ischemia occurs when blood flow to the brain is halted or drastically reduced. This is commonly caused by cardiac arrest. If sufficient circulation is restored within a short period of time, symptoms may be transient. However, if a significant amount of time passes before restoration, brain damage may be permanent. While reperfusion may be essential to protecting as much brain tissue as possible, it may also lead to reperfusion injury. Reperfusion injury is classified as the damage that ensues after restoration of blood supply to ischemic tissue. The symptoms of brain ischemia reflect the anatomical region undergoing blood and oxygen deprivation. Ischemia within the arteries branching from the internal carotid artery may result in symptoms such as blindness in one eye, weakness in one arm or leg, or weakness in one entire side of the body. Ischemia within the arteries branching from the vertebral arteries in the back of the brain may result in symptoms such as dizziness, vertigo, double vision, or weakness on both sides of the body. Other symptoms include, difficulty speaking, slurred speech, and the loss of coordination. The symptoms of brain ischemia range from mild to severe. Further, symptoms can last from a few seconds to a few minutes or extended periods of time. If the brain becomes damaged irreversibly and infarction occurs, the symptoms may be permanent. Multiple cerebral ischemic events may lead to subcortical ischemic depression, also known as vascular depression. This condition is most commonly seen in elderly depressed patients. Late onset depression is increasingly seen as a distinct sub-type of depression, and can be detected with an MRI. Brain ischemia has been linked to a variety of diseases or abnormalities. Individuals with sickle cell anemia, compressed blood vessels, ventricular tachycardia, plaque buildup in the arteries, blood clots, extremely low blood pressure as a result of heart attack, and congenital heart defects have a higher predisposition to brain ischemia in comparison their healthy counterparts. Sickle cell anemia may cause brain ischemia associated with the irregularly shaped blood cells. Sickle shaped blood cells clot more easily than normal blood cells, impeding blood flow to the brain. Compression of blood vessels may also lead to brain ischemia, by blocking the arteries that carry oxygen to the brain. Tumors are one cause of blood vessel compression. Ventricular tachycardia represents a series of irregular heartbeats that may cause the heart to completely shut down resulting in cessation of oxygen flow. Further, irregular heartbeats may result in formation of blood clots, thus leading to oxygen deprivation to all organs. Blockage of arteries due to plaque buildup may also result in ischemia. Even a small amount of plaque build up can result in the narrowing of passageways, causing that area to become more prone to blood clots. Large blood clots can also cause ischemia by blocking blood flow. A heart attack can also cause brain ischemia due to the correlation that exists between heart attack and low blood pressure. Extremely low blood pressure usually represents the inadequate oxygenation of tissues. Untreated heart attacks may slow blood flow enough that blood may start to clot and prevent the flow of blood to the brain or other major organs. Extremely low blood pressure can also result from drug overdose and reactions to drugs. Therefore, brain ischemia can result from events other than heart attacks. Congenital heart defects may also cause brain ischemia due to the lack of appropriate artery formation and connection. People with congenital heart defects may also be prone to blood clots. Recently, Moyamoya disease has also been identified as a potential cause for brain ischemia. Moyamoya disease is an extremely rare cerebrovascular condition that limits blood circulation to the brain, consequently leading to oxygen deprivation. During brain ischemia, the brain cannot perform aerobic metabolism due to the loss of oxygen and substrate. The brain is not able to switch to anaerobic metabolism and because it does not have any long term energy stored the levels of adenosine triphosphate (ATP) drop rapidly and approach zero within 4 minutes. In the absence of biochemical energy, cells begin to lose the ability to maintain electrochemical gradients. Consequently, there is a massive influx of calcium into the cytosol, a massive release of glutamate from synaptic vesicles, lipolysis, calpain activation, and the arrest of protein synthesis. Additionally, removal of metabolic wastes is slowed. The interruption of blood flow to the brain for ten seconds results in the immediate loss of consciousness. The interruption of blood flow for twenty seconds results in the stopping of electrical activity. Alteplase (tpa) is an effective medication for acute ischemic stroke. When given within 4.5 hours, treatment with tpa significantly improves the probability of a favourable outcome versus treatment with placebo. The outcome of brain ischemia is influenced by the quality of subsequent supportive care. Systemic blood pressure (or slightly above) should be maintained so that cerebral blood flow is restored. Also, hypoxaemia and hypercapnia should be avoided. Seizures can induce more damage; accordingly, anticonvulsants should be prescribed and should a seizure occur, aggressive treatment should be undertaken. Hyperglycaemia should also be avoided during brain ischemia. When someone presents with an ischemic event, treatment of the underlying cause is critical for prevention of further episodes. Operative procedures such as carotid endarterectomy and carotid stenting may be performed if the patient has a significant amount of plaque in the carotid arteries associated with the local ischemic events. Therapeutic hypothermia has been attempted to improve results post brain ischemia. This procedure was suggested to be beneficial based on its effects post cardiac arrest. Evidence supporting the use of therapeutic hypothermia after brain ischemia, however, is limited. A closely related disease to brain ischemia is brain hypoxia. Brain hypoxia is the condition in which there is a decrease in the oxygen supply to the brain even in the presence of adequate blood flow. If hypoxia lasts for long periods of time, coma, seizures, and even brain death may occur. Symptoms of brain hypoxia are similar to ischemia and include, inattentiveness, poor judgment, memory loss, and a decrease in motor coordination. Potential causes of brain hypoxia are suffocation, carbon monoxide poisoning, severe anemia, and use of drugs such as cocaine and other amphetamines. Other causes associated with brain hypoxia include drowning, strangling, choking, cardiac arrest, head trauma, and complications during general anesthesia. Treatment strategies for brain hypoxia vary depending on the original cause of injury. - ^ Sullivan, Jonathon. "What is Brain Ischemia?". WSU Emergency Medicine Cerebral Resuscitation Laboratory. http://sullydog.com/sullysites/qm/brainischemia101syllabus/syllabus/presentation1_9_1.html. Retrieved 2008-11-11. - ^ "Brain Ischemia (Cerebral Ischemia)". Cure Hunter Incorporated. 2003. pp. Relationship Network. http://www.curehunter.com/public/keywordSummaryD002545.do. Retrieved 2008-11-11. - ^ a b "UpToDate Inc.". http://www.uptodate.com/online/content/topic.do?topicKey=cva_dise/8834&linkTitle=Brain%20ischemia&source=preview&selectedTitle=4~132&anchor=5#5. - ^ "Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study". Journal of Cerebral Blood Flow & Metabolism. Journal of Cerebral Blood Flow & Metabolism. 2009. http://www.nature.com/jcbfm/journal/v25/n6/full/9600073a.html. Retrieved 2009-03-05. - ^ a b Raichle, Marcus (1983). "The Pathophysiology of Brain Ischemia". Neurological Progress. http://www.nil.wustl.edu/labs/raichle/MER_chapters/C55_The%20Pathophysiology%20of%20Brain%20Ischemia.pdf. Retrieved 2008-11-11. - ^ Raichle, Marcus; Ann Neurol (1983). "The pathophysiology of brain ischemia". Neurological Process. http://www.nil.wustl.edu/labs/raichle/MER_chapters/C55_The%20Pathophysiology%20of%20Brain%20Ischemia.pdf. Retrieved 2009-04-22. - ^ a b Sullivan, Jonathon. "Two Flavors of Ischemia". Brain Ischemia 101 (Emergency Medicine Cerebral Resuscitation Lab). http://sullydog.com/sullysites/qm/brainischemia101syllabus/syllabus/presentation1_9_2.html. Retrieved 2008-10-13. - ^ "Spreading depression and focal brain ischemia induce cyclooxygenase-2 in cortical neurons through N-methyl-d-aspartic acid-receptors and phospholipaseA2". PubMed Central (PNAS). 1997-08-10. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=21079. Retrieved 2009-02-08. - ^ a b Beers, Mark; Andrew Fletcher, Thomas Jones, Robert Porter (2003). The Merck Manual of Medical Information. New York, New York: Merck & Co. Inc. pp. 458–461. ISBN 8449433592. - ^ Caplan, Louis; Scott Kasner, John Dashe. "Differential diagnosis of brain ischemia". Up to Date For Patients (UpToDate). http://www.uptodate.com/patients/content/topic.do?topicKey=cva_dise/9854. Retrieved 2008-11-11. - ^ Lipton P (1999). "Ischemic cell death in brain neurons". Physiol. Rev. 79 (4): 1431–568. PMID 10508238. http://physrev.physiology.org/cgi/content/full/79/4/1431. - ^ Baldwin, Robert (2004). "Is vascular depression a distinct sub-type of depressive disorder? A review of causal evidence". International Journal of Geriatric Psychiatry (John Wiley & Sons). http://www3.interscience.wiley.com/journal/109800791/abstract?CRETRY=1&SRETRY=0. Retrieved 2008-11-13. - ^ Sparks, Gareth (2002). "What is Moyamoya disease?". eSSORTMENT. http://www.essortment.com/family/moyamoyamoyadi_sxma.htm. Retrieved 2009-04-13. - ^ Sullivan, Jonathon. "Bad Things Happen in Ischemia". WSU Emergency Medicine Cerebral Resuscitation Laboratory (Emergency Medicine Cerebral Resuscitation Lab). http://sullydog.com/sullysites/qm/brainischemia101syllabus/syllabus/presentation1_9_7.html. Retrieved 2008-11-11. - ^ "Ischemic and Hemorrhagic". http://www.umassmed.edu/strokestop/module_one/Ischemic_Hemorrhagic.html. Retrieved 2008-11-11. - ^ Hinds, CJ (1985-09-21). "Prevention and Treatment of Brain Ischemia". Pubmed. pp. 758–759. http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1417168&blobtype=pdf. Retrieved 2009-04-27. - ^ a b "Cerebral Hypoxia Information Page". National Institute of Neurological Disorders and Stroke (National Institutes of Health). 2008-05-07. http://www.ninds.nih.gov/disorders/anoxia/anoxia.htm. Retrieved 2009-04-28. - Veronika I. Skvortsova; Eugene I. Gusev; Skvortsova, Veronica I. (2003). Brain ischemia. New York: Kluwer Academic/Plenum Publishers. ISBN 0-306-47694-0. - An extensive review of mechanisms by which ischemia damages the nervous system has been published by Peter Lipton. - Chang, Steven; Doty, James; Skirboll, Stephen; Steinberg, Gary. Cerebral ischemia . cgi.stanford.edu. URL last accessed February 26, 2006. - Ramirez, Robert; Gulli, Laith. Encyclopedia of Neurological Disorders: Hypoxia. health.enotes.com. URL last accessed February 26, 2006. (PDF format) CNS disease, Vascular disease: Cerebrovascular diseases (G45–G46 and I60–I69, 430–438) Brain ischemia/ Aneurysm Other/general Pathology: hemodynamics Decreases Increasesgeneral Bruise/Hematoma: Petechia · Purpura · Ecchymosis regional: head (Epistaxis, Hemoptysis, Intracranial hemorrhage, Hyphema, Subconjunctival hemorrhage) · torso (Hemothorax, Hemopericardium, Pulmonary hematoma) · abdomen (Gastrointestinal bleeding, Haemobilia, Hemoperitoneum, Hematocele, Hematosalpinx ) · joint (Hemarthrosis)Other Wikimedia Foundation. 2010. Look at other dictionaries: Ischemia — Vascular ischemia of the toes with characteristic cyanosis. In medicine, ischemia (from Greek ισχαιμία, ischaimía; isch root denoting a restriction or thinning or to make or grow thin/lean, haema blood) is a restriction in blood supply, generally … Wikipedia Brain herniation — Classification and external resources MRI showing injury due to brain herniation ICD 10 G … Wikipedia Brain-specific angiogenesis inhibitor 2 — Brain specific angiogenesis inhibitor 2, also known as BAI2, is a human gene.cite web \| title = Entrez Gene: BAI2 brain specific angiogenesis inhibitor 2\| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene Cmd=ShowDetailView TermToSearch=576\| … Wikipedia ischemia — noun Etymology: New Latin ischaemia, from ischaemus styptic, from Greek ischaimos, from ischein to restrain (akin to Greek echein to hold) + haima blood more at scheme Date: 1855 deficient supply of blood to a body part (as the heart or brain)… … New Collegiate Dictionary Ischemia — Inadequate blood supply (circulation) to a local area due to blockage of the blood vessels to the area. * * * Local anemia due to mechanical obstruction (mainly arterial narrowing or disruption) of the blood supply. [G. ischo, to keep back, +… … Medical dictionary Traumatic brain injury — See also: Brain injury (disambiguation) Traumatic brain injury Classification and external resources … Wikipedia Mesenteric ischemia — Classification and external resources ICD 10 K55.9 ICD 9 557.9 … Wikipedia Primary and secondary brain injury — are ways to classify the injury processes that occur in brain injury. In traumatic brain injury (TBI), primary injury occurs during the initial insult, and results from displacement of the physical structures of the brain. On the other hand,… … Wikipedia Acquired brain injury — thumb\|right\|Parasagittal MRI of the head in a patient with benign familial macrocephaly before brain injury.A neurological condition, Acquired Brain Injury ( ABI ) is damage to the brain acquired after birth. It usually affects cognitive,… … Wikipedia respirator brain — the congested, swollen brain of a patient who has been on a respirator longer than one day after suffering cerebral anoxia and ischemia; necrotic and autolytic changes begin to occur and the patient is comatose or brain dead … Medical dictionary	2	7	2	0	0	5	0.923228	7	4,129
Read your latest personalised notifications No account yet? Start here Don't miss out Ok, got it Table of contents 3. Pathophysiology - Mechanism of Disease in Relation with the Cardiovascular System 4. Strategies for Diagnosing SARS-CoV-2 5. Protective Measures for Health Care Personnel and Patients in Cardiology 6. Triage Systems (Reorganization and Redistribution) 7. Diagnosis of Cardiovascular Conditions in COVID-19 Patients 8. Categorization of Emergency/Urgency of Invasive Procedures 9. Management/Treatment Pathways 10. Treatment of SARS-CoV-2 infection 11. Patient Information 13. List of Figures 14. List of Tables 15. List of References Last updated on 10 June 2020 Download document as PDF Submit your comments Download change history log The SARS-CoV‑2 causing COVID-19 has reached pandemic levels since March 2020. In the absence of vaccines or curative medical treatment, COVID-19 exerts an unprecedented global impact on public health and health care delivery. Owing to the unexpected need for large capacities of intensive care unit (ICU) beds with the ability to provide respiratory support and mechanical ventilation, temporary redistribution and reorganization of resources within hospitals have become necessary with relevant consequences for all medical specialties. In addition, protective measures against SARS-CoV‑2 gain particular significance for health care personnel (HCP) in direct contact with patients suffering from COVID-19 as well as for ambulatory and hospitalized patients without infection. In view of finite health care resources, health care providers are confronted with ethical considerations on how to prioritize access to care for individual patients as well as providing care for COVID-19 while not neglecting other life-threatening emergencies. Of note, assays to detect the virus in asymptomatic and symptomatic patients have important limitations in terms of sensitivity and specificity and will be complemented by tests for antibodies to identify those that already have been infected previously. SARS-CoV‑2 not only causes viral pneumonia but has major implications for the CV system. Patients with CV risk factors including male sex, advanced age, diabetes, hypertension and obesity as well as patients with established CV and cerebrovascular disease have been identified as particularly vulnerable populations with increased morbidity and mortality when suffering from COVID-19. Moreover, a considerable proportion of patients may develop cardiac injury in the context of COVID-19 which portends an increased risk of in-hospital mortality. Aside from arterial and venous thrombotic complications presenting as acute coronary syndromes (ACS) and venous thromboembolism (VTE), myocarditis plays an important role in patients with acute heart failure (HF). Moreover, a wide range of arrhythmias has been reported to complicate the course of COVID-19 including potential pro-arrhythmic effects of medical treatment targeted at COVID-19 and associated diseases. Owing to redistribution of health care resources, access to emergency treatment including reperfusion therapy may be affected depending on the severity of the epidemic at a local level. This is further aggravated by increasing concerns of delayed presentation of CV emergencies as patients are afraid to seek medical attention during the pandemic. For all these reasons, the European Society of Cardiology (ESC) has assembled a group of experts and practitioners with experience in the care of COVID-19 patients to provide a guidance document relevant for all aspects of CV care during the COVID-19 pandemic. While the document is comprehensive, it is important to point the reader to what the document is unable to do and what the limitations are: By 10 March 2020, 4296 persons world-wide had died from COVID-19 infection. By 7 May, 3.67 million had tested positive and more than 250 000 had died.1 The overall case-fatality rate is very country-specific for COVID-19 infection and depending on the phase of the epidemic, testing, registration, demography, healthcare capacity and governmental decisions.2 For most countries, it is uncertain how the registration is organized which makes the comparison of case-fatality rates between countries difficult. The excess death rate is a more reliable approach to compare the impact of the COVID-19 pandemic in different countries. An article in the New York Times demonstrated that there are large differences in the excess date rates. Germany has only an excess death rate of 4% which is surprisingly low in comparison with other countries or cities such as Italy (49%), the United Kingdom (65%) (UK), Spain (67%) or New York City (297%).3 Furthermore, COVID-19 infection has similar infection rates in both sexes; however, mortality rates are higher in men.4 Daily situation reports of the COVID-19 pandemic are disseminated by the WHO on their website. After the start of the COVID-19 pandemic in Wuhan, China, the epicenter of the epidemic is now in Europe. Figure 1 gives an overview of the evolution of laboratory-confirmed cases of COVID-19 in Europe. A large Chinese study analyzed 72 314 patient records which consisted of 44 672 (61.8%) confirmed cases, 16 186 (22.4%) suspected cases, and 889 (1.2%) asymptomatic cases.4 Among confirmed cases in this study, 12.8% had hypertension, 5.3% diabetes and 4.2% CVD.4 Strikingly, these numbers are lower than the prevalence of CVD risk factor in a typical Chinese population, but it is important to mention that these are not age-adjusted and 53% of cases had missing data on comorbidities.5 A study including 5700 patients from New York City, Long Island, and Westchester County (United States of America (USA)) reported a similar message that hypertension (56.6%), obesity (41.7%), diabetes (33.8%), coronary artery disease (11.1%) and congestive heart failure (6.9%) were the most common comorbidities.6 In comparison, the prevalence of hypertension, obesity and diabetes in the general population in the USA is respectively 45%, 42.4% and 10.5%.7-9 In early retrospective analysis based on data from 138 patients in Wuhan, China, approximately 50% of patients with COVID-19 infection had one or more comorbidities.10 Moreover, in patients admitted with a severe COVID-19 infection this proportion was as high as 72%.10 It remains vague whether diabetes, hypertension and CVD are causally linked or associated due to age.6 However, an important message is the fact that patients who develop severe disease are more likely to be vulnerable because of comorbid disease, including CVD. Ethnicity seems to be linked to susceptibility and outcomes of a COVID-19 infection.11, 12 Data from the United Kingdom show that one third of patients admitted to an intensive care unit due to COVID-19 infection were from an ethnic minority background.11, 13 Reports from the USA reveal the same message that ethnic minority groups have also been disproportionately affected by COVID-19 infections.12 There are multiple potential mechanisms such socioeconomic, cultural, or lifestyle factors and genetic predisposition. Also, pathophysiological differences in susceptibility or response to infection such as increased risk of admission for acute respiratory tract,14 an increased prevalence of vitamin D deficiency,15 increased inflammatory burden, and higher prevalence of cardiovascular risk factors such as insulin resistance and obesity than in white populations.11, 16 Verity et al.17 estimated that the case fatality ratio in China (adjusted for demography) was 1.38% but estimated case-fatality depends very much on the testing strategy of non-severe cases as many cases remain unverified. Case-fatality is highest in older age groups: The case fatality ratio was 0.32 in patients aged < 60 years of age in comparison with 6.4% in patients aged > 60 years.17 In Italy case fatality ranged from 0% below age 30 years to 3.5% for age 60–69 years and 20% above age 80 years.18 Higher mortality of a COVID-19 infection in older age groups was also revealed in an American dataset.6 This underlines the fact that increasing age is an important risk factor for severe course of COVID-19 infections. Underlying CVD is also associated with higher risk for a severe COVID-19 infection. In a retrospective cohort study of 72 314 cases in China19 patients with CV comorbidities had fivefold higher mortality risk (10.5%), however, without age adjustment. Multinational cohort analyses will give more insights in the prevalence and risk of CV comorbidities in COVID-19 infection. There are several potential mechanisms explaining why the course of the disease is more severe in patients with underlying CV risk factors and CVD.20 These are described in sections 3 and 9. Preceding coronaviruses outbreaks such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) were associated with a significant burden of CV comorbidities and complications.20,21 Common cardiac complications in SARS were hypotension, myocarditis, arrhythmias, and sudden cardiac death (SCD).22,23 Diagnostic workup during SARS infection revealed electrocardiographic changes, sub-clinical left ventricular (LV) diastolic impairment and troponin elevation. MERS was associated with myocarditis and HF.22 COVID-19 infection seems to have comparable cardiac manifestations. Autopsies of patients with COVID-19 infection revealed infiltration of the myocardium by interstitial mononuclear inflammatory cells.24 COVID-19 infections are associated with increased cardiac biomarkers levels due to myocardial injury.24-26 The myocardial injury and the increased levels of biomarkers are likely associated with infection-induced myocarditis and ischaemia.27 In a study by Shi et al.26 in 416 patients of whom 57 died, cardiac injury was a common finding (19.7%). In the patients who died, 10.6% had coronary artery disease (CAD), 4.1% had HF, and 5.3% had cerebrovascular disease.26 Moreover, in multivariable adjusted models, cardiac injury was significantly and independently associated with mortality (hazard ratio [HR]: 4.26).26 Similarly, in a study by Guo et al.25, elevated troponin T levels due to cardiac injury was associated with significantly higher mortality. These patients were more likely to be men, to be older and to have more comorbidities such as hypertension, coronary heart disease.25 Severe COVID-19 infections are also potentially associated with cardiac arrhythmias at least in part due to infection-related myocarditis.10 Next to acute complications, COVID-19 infection may also be linked with an elevated long-term CV risk. It is well established that in patients with pneumonia, hypercoagulability and systemic inflammatory activity can persist for a long period.2,20 Moreover, follow-up studies of the SARS epidemic demonstrated that patients with a history of SARS-coronavirus infection often had hyperlipidaemia, CV system abnormalities or glucose metabolism disorders.20-22 However, SARS was treated with pulses of methylprednisolone which could be the explanation for the long-term perturbation of lipid metabolism rather than a consequence of the infection itself.24 Naturally, no long term effects of a COVID-19 infection are known yet but these effects of a SARS-coronavirus infection justify surveillance of recovered COVID-19 infection patients. COVID-19 is caused by a novel betacoronavirus officially named by the WHO as SARS-CoV‑2. Coronaviruses are enveloped, single-stranded ribonucleic acid (RNA) viruses with surface projections that correspond to surface spike proteins.28 The natural reservoir of SARS-CoV‑2 seems to be the chrysanthemum bat,29 but the intermediate host remains unclear. SARS-CoV‑2 is highly virulent and the transmission capacity is greater than the previous SARS virus (outbreak in 2003), with high abundance in infected people (up to a billion RNA copies/mL of sputum) and long-term stability on contaminated surfaces.30 SARS-CoV‑2 is more stable on plastic and stainless steel than on copper and cardboard, and viable virus has been detected for up to 72 hours after application to these surfaces.30 While the infectivity of SARS-CoV‑2 is greater than that of influenza or SARS-coronavirus, more data are needed for accurate assessment.31 Transmission occurs primarily by a combination of spread by droplet, and direct and indirect contact, and may possibly be airborne as well. The viral incubation period is 2–14 days, (mostly 3–7 days).32 It is contagious during the latency period. SARS-CoV‑2 can initially be detected 1–2 days prior to onset of upper respiratory tract symptoms. Mild cases were found to have an early viral clearance, with 90% of these patients repeatedly testing negative on reverse transcriptase polymerase chain reaction (RT-PCR) by day 10 post-onset. By contrast, all severe cases still tested positive at or beyond day 10 post-onset.33 Median duration of viral shedding was 20 days (interquartile range: 17–24) in survivors.34 The longest observed duration of viral shedding in survivors was 37 days.34 The host receptor through which SARS-CoV‑2 enters cells to trigger infection is ACE2 (Figure 2).35,36 ACE2 is a multifunctional protein. Its primary physiological role is the enzymatic conversion of angiotensin (Ang) II to Ang-(1–7), and Ang I to Ang-(1–9), which are CV protective peptides.37 In the context of COVID-19, however, ACE2 is also involved in SARS through its function as the coronavirus receptor.38 Binding of the SARS-CoV‑2 spike protein to ACE2 facilitates virus entry into lung alveolar epithelial cells, where it is highly expressed, through processes involving cell surface associated transmembrane protein serine 2 (TMPRSS2)39 (Figure 2). Within the host cell cytoplasm, the viral genome RNA is released and replicates leading to newly formed genomic RNA, which is processed into virion-containing vesicles that fuse with the cell membrane to release the virus. SARS-CoV‑2 is spread mainly through the respiratory tract by droplets, respiratory secretions and direct contact. The RAS/ACE2 seems to be disrupted by SARS-CoV‑2 infection, which likely plays a pathogenic role in severe lung injury and respiratory failure in COVID-19.40 In addition to the lungs, ACE2 is highly expressed in human heart, vessels and gastrointestinal tract.41,42 COVID-19 is primarily a respiratory disease, but many patients also have CVD, including hypertension, acute cardiac injury and myocarditis (Figure 3 from Guzik et al.43).21,44 This may be secondary to the lung disease, since acute lung injury itself leads to increased cardiac workload and can be problematic especially in patients with pre-existing HF. CVD may also be a primary phenomenon considering the important (patho)physiological role of the RAS/ACE2 in the CV system and the fact that ACE2 is expressed in human heart, vascular cells and pericytes.45 The prevalence of pre-existing hypertension seems to be higher in COVID-19 patients who develop severe disease versus those who do not.34,46 This seems to also be true for acute respiratory distress syndrome (ARDS) or death. These earlier studies were not age-adjusted and the impact of age still needs to be addressed. The mechanisms underlying potential relationships between hypertension and COVID-19 are thought most likely to relate confounding due to age and associated comorbidities.47 Previous speculation proposed that treatment of hypertension with RAS inhibitors may influence SARS-CoV‑2 binding to ACE2, promoting disease.48 This is based on some experimental findings that RAS inhibitors cause a compensatory increase in tissue levels of ACE2,49 and that ACE-inhibitors or ARBs may be detrimental in patients exposed to SARS-CoV-2.50 It is however important to emphasize that there is no clear evidence that using angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) lead to up-regulation of ACE2 in human tissues. The available data from blood samples suggest that there is no association between circulating levels of ACE2 and use of RAAS antagonists.51 It also appears that in experimental models ARBs may have a potentially protective influence.52,53 A recent observational study of over 8910 patients from 169 hospitals in Asia, Europe, and North America, did not show a harmful association of ACEIs or ARBs with in-hospital mortality,54 while a Wuhan study demonstrated that in 1128 hospitalized patients use of ACEI/ARB was associated with lower risk of COVID-19 infection or serious complication or deaths from COVID-19 infection.47, 54-60 The recent data are all-cause mortality compared with ACEI/ARB non-users.60 This is in line with prior guidance from major CV Societies, that stated that patients on ACEIs or ARBs should not stop their treatment.51,61 Myocarditis appears in COVID-19 patients several days after initiation of fever. This indicates myocardial damage caused by viral infection. Mechanisms of SARS-CoV-2-induced myocardial injury may be related to upregulation of ACE2 in the heart and coronary vessels.44,61 Respiratory failure and hypoxia in COVID-19 may also cause damage to the myocardium and immune mechanisms of myocardial inflammation may be especially important.27,44,61 For example, cardiac injury leads to activation of the innate immune response with release of proinflammatory cytokines, as well as to the activation of adaptive auto-immune type mechanisms through molecular mimicry. Inflammatory mechanisms and activation of immune responses underlie a large range of CVDs including atherosclerosis, HF and hypertension.62,63 This dysregulation may have different degrees in COVID-19. Firstly another receptor through which SARS-CoV‑2 may enter cells is cluster of differentiation 209 (CD209).64 CD209 is expressed in macrophages promoting virus invasion into immune cells in cardiac and vascular tissues. More importantly, in severe cases of COVID-19, systemic increases of numerous cytokines including IL-6 IL-2, IL-7, granulocyte colony-stimulating factor, C-X-C motif chemokine 10 (CXCL10), chemokine (C-C motif) ligand 2, and tumour necrosis factor-α have all been observed in subjects with COVID-19,65 which corresponds to the characteristics of a cytokine release syndrome (CRS). Altered vascular permeability can result in non-cardiogenic pulmonary oedema and promotes ARDS as well as multi-organ dysfunction. High serum IL-6 levels are a common feature in CRS. IL-6 is a clinical predictor of mortality in COVID-19.66 Thus IL-6 targeting may be permissive for use in COVID-19 to tackle the CRS. Finally, it has been shown that hypertension is associated with circulating lymphocytes in patients67 and CD8 T cell dysfunction with development of CVD.68 CD8 T cells are a pillar of antiviral immunity, thus their dysfunction can make the organism inefficiently target virally infected cells. As evidenced by previous epidemics, including SARS and MERS, highly sensitive and specific laboratory diagnostics are essential for case identification, contact tracing, animal source finding, and efficient and rational containment measures.69 Precise case identification is essential in order to isolate vulnerable individuals. Based on current epidemiological analysis, CVD conveys risk of a more severe outcome of COVID-19;21,44 therefore, testing should be particularly widely considered in CVD patients. Moreover, in similarity to influenza, efficient testing of carers and people in contact with high risk patients may allow protection of subjects with multiple comorbidities. The decision to test should be based on clinical and epidemiological factors and linked to an assessment of the likelihood of infection, in particular when availability of tests is limited. Available testing strategies are outlined below (Table 1). While isolation of the virus itself using electron microscopy would be the most specific diagnostics, it requires biosafety level-3 facilities which are not available in most healthcare institutions. Serum antibody and antigen detection tests would be the easiest and fastest, but have not yet been validated, and there may be cross-reactivity with other coronaviruses, especially SARS-coronavirus. Furthermore, antibodies are not measurable in the initial phase of the infection. Therefore, real-time PCR remains the most useful laboratory diagnostic test for COVID-19 worldwide. Comparative specificity and sensitivity of these tests needs to be carefully assessed, when more data is available. It is important to note that negative results of molecular testing (RT-PCR) do not preclude SARS-CoV‑2 infection and should not be used as the sole basis for patient management decisions but must be combined with clinical observations, patient history, and epidemiological information. There are a number of factors that may lead to a negative result in an infected individual. These include poor quality of the specimen (small material), collection late or very early in the infection, poor handling/shipping as well as technical reasons inherent in the test such as virus mutation or PCR inhibition. Therefore, retesting is recommended after 48 hours in clinically suspected cases that test negative. It is essential that adequate standard operating procedures are in use and that staff are trained for appropriate specimen collection, storage, packaging, and transport. This must be observed in order for testing to be reliable and safe for staff and patients. The optimal testing material includes nasal swab rather than pharyngeal. In order to obtain a sufficiently deep swab, the sample must be obtained by experienced and trained staff. According to a comparative study using lung CT as comparator, the sensitivity of nasopharyngeal swab may be limited to 60–70%.72 It has also been concluded that the test does not seem to change clinical decisions and diagnostic considerations in subjects with pretest probability exceeding 60–70% (e.g. subjects with positive epidemiological and clinical criteria fulfilled). This however does not indicate that such tests should not be performed to confirm infection, but it is important that the test is repeated if there is clinical suspicion of COVID-19 infection. Lung CT has a high sensitivity for diagnosis of COVID-19 in hospitalized patients who are RT-PCR positive. In a study undertaken between 06 January and 06 February 2020 in Tongji Hospital, Wuhan, China, in a population of 1014 patients – when using RT-PCR as a reference, the sensitivity of lung CT imaging for COVID-19 was 97%.72 Importantly, 60–93% of patients had initial positive lung CT consistent with COVID-19 before the initial positive RT-PCR results. Nucleic acid shedding is also an important tool to verify patient improvement, although 42% of patients showed improvement of follow-up lung CT scans before the RT-PCR results turning negative.72 It is important, however, that nucleic acid shedding does not always indicate presence of live virus. Widespread testing strategies included drive-through testing in South Korea. However, testing capacity may be insufficient. Thus testing priorities have been suggested by individual health systems such as one proposed by Centers for Disease Control for the United States (US) (Table 2). Sample pooling strategy has been proposed in relation to sample collection as the most cost-efficient tool for population-wide screening, for example at airports. Taking into account that there are only a few documents regarding type and level of protection of HCP, the ESC Guidance Document considered the WHO document,73 the American Center for Disease Control and Prevention guidelines on COVID-19,74 the European Centre for Disease Control guidelines on COVID-19;75 but also Chinese data76,77 and experiences from European countries with the largest outbreaks of COVID-19. Importantly, the ESC Guidance document aims to suggest a high level of protection for HCP in the worst transmission scenario of SARS-CoV‑2 infection. Different settings, such as countries with no cases, countries with sporadic cases, countries experiencing case clusters in time, geographic location and/or common exposure should prepare to respond to different public health scenarios, recognizing that there is no one size fits all approach to managing cases and outbreaks of COVID-19. Each country should dynamically assess its risk and rapidly change the definitions according to their local situation, depending on the phase of the epidemic, demography, healthcare capacity, and governmental/local health authorities’ decisions. In a recent report related to 138 confirmed COVID-19 cases, 41.3% were considered acquired infection from the hospital, and more than 70% of these patients were HCP.78 Health care workers are in fact at increased risk for contracting the virus, as demonstrated by Wu and colleagues, who reported that in China 1716 of the 44 672 (3.8%) infected individuals were professionals (see later).19 Generally, protection against COVID-19 needs to be differentiated according to the level of risk based on patient presentation, type of procedures and interaction and HCP risk status. Table 3 provides general recommendations. The precautions taken depend on COVID-19 case definition as defined in Table 4. The level of protection of HCP depends on patient risk status, setting and procedure performed (Table 5). In addition to personal protective equipment (PPE) for HCP, all suspected/probable or confirmed SARS-CoV‑2 patients should wear a disposable surgical mask when in room with HCP or other persons. FFP3, FFP2 and N95 are designed to achieve a very close facial fit and very efficient filtration of airborne particles. Powered air-purifying respirator (PAPR) is a type of PPE consisting of a respirator in the form of a hood, which takes ambient air contaminated with pathogens, actively filters these hazards, and delivers the clean air to the user's face and mouth (Figure 4). All HCP should be well-versed in proper techniques for donning and removing PPE including eye protection (Figure 5 and Figure 6).77 Because there is no time to wait for nasopharyngeal swab result, the procedure should be performed in a dedicated COVID-19 catheterization laboratory if available and patients should be triaged according to Table 4. In regions with high rates of community transmission, it is reasonable to regard all patients as possible SARS-CoV‑2 positive and HCP protected accordingly (Table 5) Most of the electrophysiology (EP) activity is being markedly reduced or suspended in areas that have been severely affected by COVID-19 outbreak. Residual EP activity should be maintained for selected categories of patients (Table 7 and Table 13). Protection of the HCP:83 The major issue is that the viral load in the airway is probably very high and very contagious.84 This poses significant risks for HCP performing non-invasive ventilation by CPAP or invasive ventilation with orotracheal intubation. Accordingly, a high level of vigilance is necessary to prevent contracting the infection when managing patients using CPAP, when intubation is performed or the transesophageal echocardiogram (TEE) probe is inserted. It is now well known that CV patients who develop a COVID-19 infection have a higher risk of poor in-hospital outcome.20 This is why it is mandatory to effectively protect them from being in contact with infected subjects whose COVID-19-related symptoms are still not evident or not specific. Wang et al reported a significant percentage of hospital-associated transmission of the virus (12.3% of all patients) in a cohort of hospitalized patients with novel coronavirus-infected pneumonia in Wuhan, China at the start of the pandemic.10 Based on this data, patients accessing the hospital for an acute cardiac disease with no signs or symptoms of viral infection should complete their diagnostic workflow in a clean area and finally access a COVID-19-free ward. All the measures to keep chronic cardiac outpatients at home as much as possible as well as to limit in-hospital stay of cardiac patients to the shortest acceptable time should be implemented. The adoption of a restrictive visitor policy is also strongly recommended.85 Elective procedures should be avoided during the current COVID-19 pandemic so as not to overload the health system or increase the risk of disease propagation. In this context, in order to minimize risk for COVID-19 transmission, the use of telemedicine is highly desirable especially for vulnerable groups, such as older patients. Additionally, telemedicine provides an opportunity for tele-consultations with different specialists and professionals, thus allowing patients to receive a comprehensive therapeutic approach without moving from home to the outpatient clinic or to the hospital. Also telerehabilitation (or home based rehabilitation with telephone contact with the rehab team) is an option for patients discharged from the hospital after an acute event. Finally telemedical follow up of HF and device patients is becoming more and more standard and may be considered. Telemedicine has been considered relevant in contributing to viral outbreak containment while preventing patient health from deteriorating because of misdiagnosed or mistreated CVDs.86 Beyond telemedicine ‘home care’ and ‘mobile clinics’ are currently proposed as a way to prevent unnecessary movement of patients towards hospitals, provided that nurses and physicians wear the appropriate PPE. This solution could prevent clinical instability of many cardiac diseases (i.e. chronic HF), assure patient adherence to long-term treatment and contribute to a ‘community-centred’ form of care that might be more advantageous than a purely ‘patient-centred’ care model, where only infected, hospitalized patients consume most of the available resources of the healthcare system.87 When CV patients temporarily access the hospital facilities for diagnostic or therapeutic reasons they should always protect themselves by systematically wearing surgical masks, practicing social distancing and appropriate washing/cleaning their hands with alcoholic solutions, which should be provided by the hospital staff.88 Patients should also be protected by HCP donning surgical masks, depending on the local community prevalence of COVID-19. Patient triage is of paramount importance when medical services are overwhelmed by a pandemic and healthcare resources are limited. This is particularly true for the COVID-19 epidemic, whose outbreak is currently seriously challenging the healthcare systems across the world. Some peculiar aspects of this pandemic, potentially affecting triage of cardiac patients, should be outlined: Hub centres are committed to provide acute reperfusion to all patients requiring an urgent PCI. Patients with STEMI or high-risk NSTEMI should be triaged by the emergency medical services team and timely transported to hub centres, if feasible. As a general rule we recommend that the number of catheterization laboratories available for primary PCI should not be reduced during the pandemic, to avoid an increase in door-to-balloon time, to diminish the risk of infection during transfer for both professionals and/or patients, and to unload the health care system. Regional STEMI networks should adapt to dynamic changes of the pandemic in every region according to local medical and logistic resources. As an example, in Lombardy, Italy, a system of specialized COVID-19 referral hospitals has been defined at the start of the virus epidemic, reducing by more than 60% the number of previous referral centres with 24 hour/7 day capacity to perform a primary PCI.91 Active shifts have been also assigned to interventional cardiologists, in order to satisfy the foreseen increased number of STEMI or NSTEMI patients arriving at the hospital.92 The ambulance networks also need to be reorganized in order to bring the patients straight to the COVID-19 referral hospital, skipping the spoke centres from where a secondary transportation could be difficult to arrange and time-consuming. The major objective of this rearrangement is primarily to allow for a timely treatment of the acute CVD, despite the unavoidable epidemic-related delays. It is also functional to secure patients to COVID-19-dedicated hospitals or to hospitals with isolated COVID-19 dedicated facilities when patients with acute CVDs are highly suspect for COVID-19 infection. China has been the first country to receive specific recommendations for a transport work programme directly by the country Health Authorities.93 In countries highly affected by the COVID-19 pandemic EDs have been re-organized to provide possible COVID-19 patients with dedicated access areas and isolated facilities from their first arrival to the hospital. Local protocols for rapidly triaging patients with respiratory symptoms should be issued with the aim of differentiating patients with CVDs from COVID-19 patients. In China for example patients with no geographical or family history of virus infection, fever, respiratory symptoms, fatigue or diarrhoea were considered ‘COVID-19 unlikely’ and their CVD was usually treated with standard protocols.94 A check-list should be adopted to quickly differentiate patients with possible or probable COVID-19 infection from non-infected patients (Table 3 and Table 4). Patients with mild, stable diseases should be discharged from the ED as soon as possible (Figure 8), with the suggestion to stay at home in quarantine if a COVID-19 infection is suspected or confirmed. Conversely, patients in need of hospital admission for acute CVD with concomitant possible/probable SARS-CoV‑2 infection (Table 4) should rapidly undergo testing and be managed as SARS-CoV-2 infected until they have two negative tests within 48 hours. Patients in need of hospital admission not suspected of SARS-CoV‑2 infection can be managed according to standard of care. ICU beds are mainly devoted to complicated COVID-19 patients in need of intensive care, who frequently present with underlying CVD and poor prognosis.19,95 Provided that in a pandemic situation the ethical value of maximizing benefits is recognized as the most relevant to drive resource allocation,96 this might invariably disadvantage patients with advanced age and more severe CVD who will not be prioritized for advanced care provision. Acute CV patients who tested negative (and without clinical suspicion for) COVID-19 infection, should be accurately identified and admitted, if feasible, to dedicated areas ICUs or ICCUs free from COVID-19 patients (‘clean’ ICUs or ICCUs), particularly in COVID-19 referral hospitals. If a fully ‘clean’ facility is not available, because of overwhelming numbers of COVID-19 patients, it should be guaranteed that airborne isolation rooms are set up in the facility, effectively separating patients with COVID-19 infection from all the others to minimize their infective risk. Such organization should also allow for adequate protection of HCP and well-defined pathways to and from the isolated rooms, in order to contain the spread of infection.97 Intermediate care units (also identifiable as ICCUs level II or I according to the Association for Acute Cardiovascular Care position paper98) share the same problems of ICUs, being usually equipped with CPAP machines for non-invasive ventilation. The same solutions already discussed for ICUs are therefore also applicable to intermediate care units. Triaging CV patients in need of CPAP from COVID-19 patients with pneumonia is mandatory, but still isolated rooms for COVID-19 positive CV patients (with acute HF for example) different from rooms for COVID-19 negative CV patients are very much needed. The symptom of chest pain or tightness is common in patients with active COVID-19 infection. It is usually poorly localized and may be associated with breathlessness due to the underlying pneumonia. Associated profound hypoxaemia together with tachycardia may result in chest pain and electrocardiographic changes suggestive of myocardial ischaemia. Where biomarkers are altered, Type 2 myocardial infarction (MI) may be suggested. Patients with ACS do, however, experience the more typical symptoms related to ischaemia. The presence of a COVID-19 infection can make the differential diagnosis more difficult, as shortness of breath and respiratory symptoms may be present and may precede or precipitate cardiac signs and symptoms. Dyspnoea (shortness of breath) is one of the typical symptoms in COVID-19. Of 1099 adult inpatients and outpatients in China, 18.7% presented with dyspnoea.80 With increasing disease severity, the proportion of dyspnoea significantly increases (31–55% in hospitalized patients and up to 92% of patients admitted to ICUs).10,65 Cough is present in 59.4–81.1% of patients with COVID-19, irrespective of disease severity.34,99 Unproductive (dry) cough is more frequent, whereas sputum production is present in 23.0–33.7%.10,34,65,80 ARDS is characterized by bilateral opacifications on chest imaging (e.g. bilateral ground glass opacifications on CT) and hypoxaemia that cannot be explained by other causes.100 Among 1099 adult inpatients and outpatients in China, ARDS occurred in 3.4%,80 but in hospitalized patients, the rates are significantly higher (19.6–41.8%).10,34,99 The median time from disease onset to ARDS is 8–12.5 days.65 The risk of ARDS increases with older age (≥ 65 years old), presence of comorbidities (hypertension, diabetes), neutrophilia, lymphocytopenia, elevated laboratory markers of organ dysfunction (e.g. lactate dehydrogenase [LDH]), inflammation (C reactive protein) and D-dimer.99 Mortality of patients treated for ARDS in COVID-19 is high (e.g. 52–53%).10,34,65,66,80,99,100 An early, accurate, and rapid diagnosis of CS in patients with confirmed or suspected COVID-19 is essential.101 The exact incidence of CS in these patients is unknown. However, the median duration between onset of symptoms and admission to ICU in critically ill COVID-19 patients has been 9–10 days, suggesting a gradual respiratory deterioration in most patients.102 A simple, actionable classification scheme for CS diagnosis has recently been proposed.103 In critically ill COVID-19 patients at risk for CS (such as those with large AMI, acute decompensated HF; Society for Cardiovascular Angiography and Interventions stage A)103 and sepsis, a mixed aetiology of CS and septic shock should be considered in addition to the sole cardiogenic component. Parameters allowing for a differential diagnosis between CS and septic shock, such as the presence of vasodilatation and central venous oxygen saturation values may be assessed. In selected cases, such as in patients with unclear reasons for haemodynamic deterioration, invasive haemodynamic monitoring via a pulmonary artery catheter may provide useful information. The diagnostic work-up of critically ill patients with confirmed or suspected COVID-19 infection requires specific considerations: There is very limited literature available on the occurrence of arrhythmia in the context of an infection by the SARS-CoV‑2 virus. In a study of 138 hospitalized patients with COVID-19 in Wuhan, arrhythmia was reported in 16.7% of total patients and in 16 of 36 patients admitted to the ICU (44%), although the authors did not further specify its type.10 In a subsequent publication from the same institution, ventricular tachycardia (VT)/ventricular fibrillation (VF) was reported as a complication of the COVID-19 disease in 11 of 187 patients (5.9%), with a significantly higher incidence in patients with elevated troponin T.25 However, the largest observational study from China, with 1099 patients from 552 hospitals, did not report any arrhythmia.80 Hypoxaemia and a systemic hyperinflammation status may lead to new-onset atrial fibrillation (AF), although there are no published data so far. However, important consideration should be given to rhythm management (drug interactions with COVID-19 treatment) and anticoagulation. The clinical presentation of brady- or tachyarrhythmias in the context of COVID-19 does not differ from those previously described (i.e. palpitations, dyspnoea, dizziness, chest pain, syncope, etc.). However, there are concerns that in areas where the epidemic is extended, hospitals have experienced a significant decrease in emergency consultations for cardiac. Whether the underlying reason is concern for in-hospital contagion, a result of self-isolation measures or a saturation of the EDs and ambulances needs to be explored. Pneumonia and severe influenza infections have been associated with a markedly increased short term risk of MI and subsequent mortality, that is more common among patients at older age, nursing home resident, and patients with history of HF, coronary disease or hypertension.105-108 Moreover, for influenza epidemics it has been demonstrated that there is a consistent rise in autopsy-confirmed coronary deaths.109 Fatal AMIs have also been observed in the short term after coronavirus associated SARS.110 Notably, recent data from China suggest that myocardial injury during COVID-19 infection – as indicated by elevated troponin levels – represent one predictor of a higher risk of CV complications and an adverse clinical outcome.25,26 Moreover, an increased rate of thromboembolic events has been observed in the context of COVID-19 infection. So far no specific ECG changes have been described in patients with SARS-CoV‑2 infection. Therefore, we have to assume that the overall minimal level of myocardial injury associated with the infection (see the following section on biomarkers) does not translate into characteristic ECG manifestations in the majority of patients, although ST-segment elevation in the setting of myocarditis have been described.61 As a consequence, the same ECG diagnostic criteria for cardiac conditions apply in patients affected by SARS-CoV‑2 infection and in the general population. Little is known about COVID-19 infection and arrhythmias. One report on 138 patients described an arrhythmia (not further specified) in 16.7% and the prevalence increased to 44.4% in the 16 patients who were admitted to the ICU.10 For considerations of arrhythmia and corrected QT interval (QTc) prolongation of COVID-19 therapies see section 10.1. COVID-19 is a viral pneumonia that may result in severe systemic inflammation and ARDS, and both conditions have profound effects on the heart.26,34,111 As a quantitative marker of cardiomyocyte injury, the concentrations of cardiac troponin I/T in a patient with COVID-19 should be seen as the combination of the presence/extent of pre-existing cardiac disease AND the acute injury related to COVID-19.34,66,89,111-113 Cohort studies from patients hospitalized with COVID-19 in China showed that 5–25% of patients had elevations in cardiac troponin T/I, and this finding was more common in patients admitted to the ICU and among those who died.24-26,66,111 Concentrations remained in the normal range in the majority of survivors. In non-survivors, troponin levels progressively increased in parallel with the severity of COVID-19 and the development of ARDS (Figure 10). 24,26,34,66,111 Mild elevations in cardiac troponin T/I concentrations (e.g. < 2–3 times the ULN), particularly in an older patient with pre-existing cardiac disease, do NOT require work-up or treatment for T1MI, unless strongly suggested by angina chest pain and/or ECG changes (Figure 11). Such mild elevations are in general well explained by the combination of possible pre-existing cardiac disease AND/OR the acute injury related to COVID-19. Marked elevations in cardiac troponin T/I concentrations (e.g. > 5 times the ULN) may indicate the presence of shock as part of COVID-19, severe respiratory failure, tachycardia, systemic hypoxaemia, myocarditis, Takotsubo syndrome or T1MI triggered by COVID-19.26,34,89,111 In the absence of symptoms or ECG changes suggestive of T1MI, echocardiography should be considered in order to diagnose the underlying cause. Patients with symptoms and ECG changes suggestive of T1MI should be treated according to ESC-guidelines irrespective of COVID-19 status.24,66,113,114 BNP/NT-proBNP as quantitative biomarkers of haemodynamic myocardial stress and HF are frequently elevated among patients with severe inflammatory and/or respiratory illnesses.26,115-117 While experience in patients with COVID-19 is limited, very likely the experience from other pneumonias can be extrapolated to COVID-19.26,115-117 As quantitative markers of haemodynamic stress and HF, the concentrations of BNP/NT-proBNP in a patient with COVID-19 should be seen as the combination of the presence/extent of pre-existing cardiac disease AND/OR the acute haemodynamic stress related to COVID-19.26,115-117 At least to some extent, the release of BNP/NT-proBNP seems to be associated with the extent of right ventricular haemodynamic stress. D-dimers are generated by cleavage of fibrin monomers by prothrombin and indicate the presence of thrombin formation or reflect an unspecific acute phase response from infection or inflammation. D Dimers also may indicate the presence of disseminated intravascular coagulation associated with shock.118 It is tempting to speculate that markers of activated coagulation or impaired fibrinolysis might contribute to acute myocardial injury, eventually also affecting coronary capillaries. Therefore, markers of haemostasis including activated partial thromboplastin time, prothrombin time, fibrin degradation products and D-Dimers should be monitored routinely. In particular, elevations of D-Dimers have been associated with poor outcome.84 Although the D-dimers have a lower specificity for the diagnosis of acute PE, 32–53% of patients still have a normal D-dimer and the vast majority has D dimers below 1000 ng/ml.10,34,80 Therefore, recommended diagnostic algorithms combing pre-test probability assessment and D dimer tests can be used in case of suspected acute PE.119 In particular, algorithms applying a pre-test probability dependent D-dimer threshold may yield a decent specificity.120-122 The potential mechanisms underlying myocardial injury in those with COVID-19 infection are not fully understood. However, in keeping with other severe inflammatory and/or respiratory illnesses, direct (‘non-coronary’) myocardial injury is most likely the cause. Myocarditis, septic shock, tachycardia, severe respiratory failure, systemic hypoxaemia, Takotsubo syndrome or T1MI triggered by COVID-19, are alternative causes. Direct myocardial involvement mediated via ACE2, cytokine storm, or hypoxia induced excessive intracellular calcium leading to cardiac myocyte apoptosis have been suggested as alternative mechanisms.2,48,123 As quantitative biomarkers of haemodynamic myocardial stress and HF, intracardiac filling pressures and end-diastolic wall stress seem to be the predominant triggers of the release of BNP/NT-proBNP.115-117 As in patients without COVID-19, cardiac troponin T/I concentrations should be measured whenever on clinical grounds T1MI is suspected.113 In patients with COVID-19, diagnostic algorithms for rapid rule out and/or rule-in of MI in patients with acute chest discomfort such as the ESC high-sensitivity cardiac troponin (hs-cTn) T/I 0/1-h algorithm can be expected to provide comparable performance characteristics as in other challenging subgroups with higher baseline concentrations such as the elderly and patients with renal dysfunction: very high safety for rule-out and high accuracy for rule-in, but reduced efficacy with a higher percentage of patients remaining in the observe zone.113,124-126 Detailed clinical assessment including chest pain characteristics, assessment of COVID-19 severity, hs-cTn T/I measurement at 3 hours, and cardiac imaging including echocardiography are the key elements for the identification of MI in this heterogeneous subgroup.113,124-126 Similarly, BNP/NT-proBNP should be measured whenever on clinical grounds HF is suspected.26,115-117 In patients who are not critically ill, rule-in cut-offs for HF maintain high positive predictive value even in patients with pneumonia.26,115-117 In contrast, currently recommended cut-offs should not be applied in critically-ill patients, as most critically-ill patients have substantial elevations in BNP/NT-proBNP, most likely due to the near-universal presence of haemodynamic stress and HF in these patients.26,115-117 It is a matter of ongoing debate whether cardiac troponin T/I should be measured as a prognostic marker in patients with COVID-19. The strong and consistent association with mortality observed in the currently available reports of patients hospitalized with COVID-19, with some evidence suggesting cardiac troponin T/I even as an independent predictor of mortality, should be seen in favour of this approach.25,26,34,111 On the other hand, at this point in time, based on three arguments we consider a more conservative approach even more appropriate.26,34,66,89,111-113 First, beyond cardiac troponin T/I other routinely available clinical and laboratory variables have also emerged as strong predictors of death in COVID-19 including older age, higher Sequential Organ Failure Assessment (SOFA) score, D dimers, IL-6 and lymphocyte count. It is unlikely that cardiac troponin T/I provides incremental value to a full model. Second, there is a recent risk of inappropriate diagnostic and therapeutic interventions triggered based in cardiac troponin T/I concentrations measured for prognostic purposes. Third, in patients with COVID-19 as well as with other pneumonias or patients with ARDS, at this point in time, no specific therapeutic intervention can be justified based on the use of cardiac troponin T/I as a prognostic marker.26,34,66,89,111-113 Therefore, routine measurements of cardiac troponin T/I and/or BNP/NT-proBNP in patients with COVID-19 given the current very limited evidence for incremental value for clinical decision-making is discouraged. Non-urgent or elective cardiac imaging should not be performed routinely in patients with suspected or confirmed COVID-19 infection. Accordingly, non-urgent or elective exams should be postponed until the COVID-19 infection has ceased (Table 6).127,128 Echocardiography can be performed bedside to screen for CV complications and guide treatment. POCUS, FoCUS and critical care echocardiography are probably the preferred modalities to image patients with COVID-19. Limited evidence exists for the use of lung ultrasound to differentiate ARDS (single and/or confluent vertical artefacts, small white lung regions) from HF.129 The presence of dilated right ventricle and pulmonary hypertension may indicate contrast CT to rule out PE. In COVID-19 infected patients, echocardiography should focus solely on the acquisition of images needed to answer the clinical question in order to reduce patient contact with the machine and HCP. It should not be forgotten that the risk of infection remains in the reading rooms and therefore the material used should be also frequently sanitized. Cardiac CT should be performed when there is a potential impact on clinical management, including evaluation of symptomatic suspected CAD, acute symptomatic heart valve dysfunction, left ventricular assist device (LVAD) dysfunction, PE, urgent structural intervention.130 Cardiac CT is preferred to TEE to rule out the presence of intracardiac thrombus. In patients with acute chest pain and suspected obstructive CAD, CCTA is the preferred non-invasive imaging modality since it is accurate, fast and minimizes the exposure of patients. In patients with respiratory distress, lung CT is recommended to evaluate imaging features typical of COVID-19 and differentiate from other causes (HF, PE).94 However, it should not be used to screen for or as a first-line test to diagnose COVID-19 and should be reserved for hospitalized patients.131 A dedicated CT scanner for patients with suspected or confirmed COVID-19 is preferred. As in other imaging modalities, local standards for prevention of virus spread and protection of personnel should be followed. Many of the diagnoses can be evaluated with other imaging modalities that limit the risk of virus spread. Nuclear cardiology tests require long acquisition times and exposure of patients and personnel.132 The use of PET-CT can be limited to patients with suspected endocarditis of prosthetic valves or intracardiac devices when other imaging modalities are inconclusive or to avoid the performance of a TEE which is associated with larger risk of spreading. Single photon emission computed tomography (SPECT) or PET may also be used for diagnosing ischaemia in patients with suspected obstructive CAD when CCTA is not appropriate or available. The risks of contamination during a CMR scan is probably similar to a CT scan, but lower than during an echocardiographic study. Only clinically urgent CMR scans should be accepted.133 Longer time exposure in the scanner will probably increase the chances of contamination of equipment and staff. In order to minimize the examination time, shortened CMR protocols focused to address the clinical problem should be used.133 A dedicated MR scanner for patients with suspected or confirmed COVID-19 is a clear advantage. Allow time for a deep cleaning after each patient with suspected or confirmed COVID-19 infection. The role of CMR in COVID-19 patients is currently not clear. Accepted diagnostic indications for CMR should be considered as appropriate in these patients, but should not be performed unless clinically necessary and after a reconsideration of best suited imaging technique.128 Another important attention is the use of CMR contrast in patients with COVID-19. Renal function might be decreased in patients with COVID-19 and might contradict a clinically urgent CMR scan. One indication for an acute CMR might be suspicion of acute myocarditis, which has been reported in patients with COVID-19.134 Typical symptoms might be elevated troponins, ventricular dysfunction and/or severe arrhythmias that cannot be explained by other diagnostics and imaging methods.20 Performance of exercise testing (either conventional, Echo or nuclear) has major limitations in the COVID-19 era. During exercise the patient increases breath rate and the amount of aerosol or droplets production, even if wearing a surgical mask (that could strongly affect his/her exercise capacity). This problem is further increased since rooms of outpatient clinics are rarely large and well aerated. Performance of exercise testing is discouraged in COVID-19 suspect or positive patients and, in general, in every patient in COVID-19 epidemic or potentially epidemic areas. Alterative diagnostic methods for CAD not requiring exercise should be used as an alternative to exercise testing whenever possible. There remain conditions where exercise testing is necessary. These mainly concern patients with heart failure. Cardiopulmonary exercise testing remains the method of choice for the assessment of exercise capacity, a well-known prognostic index, and for the indication to heart transplantation in patients with heart failure. In addition, exercise testing is proposed as the method of choice for the diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with breathlessness and intermediate scores for HFpEF diagnosis. A low-level exercise may be, however, sufficient in these cases.135 In COVID-19-infected patients with clinical presentation compatible with CVD, three main entities should be considered: The rearrangement of the healthcare service required to face the COVID-19 pandemic has posed a series of relevant issues on prioritization of cardiac invasive procedures.136 Different regions in Europe and worldwide differ substantially in terms of local healthcare resources, epidemic density of the COVID-19 outbreak, changes of the epidemic over time and therefore access to healthcare services other than COVID-19 care. These differences have a wide range of implications for national/regional healthcare services, national health care authorities and in-hospital redistribution of resources. Regions (also within the same country) may be categorized into three groups according to the degree of involvement in the epidemic, with subsequent different implications for the healthcare system as summarized in Table 7. The indications provided in this document refer mainly to the scenario of heavy involvement and, in part, to the scenario of moderate involvement. Importantly, healthcare services should continue to be provided according to standard-of-care as described by current clinical practice guidelines, as long as the degree of regional involvement in the epidemic allows it. The rationale to importantly reduce the number of elective hospitalizations is three-fold: This strategy comes at the expense of time-to-treatment delays for urgent CV interventions and extension of waiting times for patients in need of elective coronary, heart valve or other CV interventions. In this context, a strategy is needed to identify patients who are in a condition allowing to postpone procedures and those who are not. An obvious concern is to maintain the standard-of-care and timely access of patients with ACS including AMI to reperfusion therapy. In patients with chronic coronary syndromes (CCS), principles of prioritization can be based on risk stratification, taking into account prognostic implications of symptoms and the presence of known critical disease of the left main stem or of the proximal left anterior descending (LAD) coronary artery at prior coronary angiogram or at CCTA.137 Similarly, patients with decompensated, symptomatic, severe aortic stenosis (AS) scheduled for transcatheter aortic valve replacement should be prioritized.138 Table 8 summarizes a categorization of invasive cardiac procedures according to urgency that may be implemented at areas affected by the COVID-19 outbreak. The management of patients with NSTE-ACS should be guided by risk stratification.113 Testing for SARS-CoV‑2 should be performed as soon as possible following first medical contact, irrespective of treatment strategy, in order to allow HCP to implement adequate protective measures and management pathways (section 5). Patients should be categorized into 4 risk groups (i.e. very high risk, high risk, intermediate risk, and low risk) and managed accordingly (Figure 12). Patients with Troponin rise and no acute clinical signs of instability (ECG changes, recurrence of pain) might be managed with a primarily conservative approach. Non-invasive imaging using CCTA may speed-up risk stratification, avoid an invasive approach139 allowing early discharge. For patients at high risk, medical strategy aims at stabilization whilst planning an early (< 24 hours) invasive strategy. The time of the invasive strategy may however be longer than 24 hours according to the timing of testing results. If feasible, a dedicated area to manage these patients while waiting for the test result should be arranged in the emergency department. In the case of positive SARS-CoV‑2 test, patients should be transferred for invasive management to a COVID-19 hospital equipped to manage COVID-19-positive patients. Patients at intermediate risk should be carefully evaluated taking into consideration alternative diagnoses to T1MI, such as Type II MI, myocarditis, or myocardial injury due to respiratory distress or multiorgan failure or Takotsubo. In the event any of the differential diagnoses seem plausible, a non invasive strategy should be considered and CCTA should be favored, if equipment and expertise are available. When there is a positive SARS-CoV‑2 test, patients should be transferred for invasive management to a COVID-19 hospital equipped to manage COVID-19-positive patients. At times of high demand on the infrastructure and reduced availability of catheterization laboratories or operators, non-invasive conservative management might be considered with early discharge from the hospital and planned clinical follow-up. The COVID-19 pandemic should not compromise timely reperfusion of STEMI patients. In line with current guidelines, reperfusion therapy remains indicated in patients with symptoms of ischaemia of < 12 hours duration and persistent ST-segment elevation in at least two contiguous ECG leads.114 Concurrently, the safety of HCP should be ensured.136 To that purpose, and in the absence of previous SARS-Co-V2 testing, all STEMI patients should be managed as if they are COVID-19 positive. We provide general guidance to address the healthcare system organization and delineate possible pathways for specific STEMI settings. The proposed actions are not evidence-based, may need to be adapted to meet local hospital and health authority regulations and may be subject to change in view of the evolving COVID-19 pandemic. While general measures for healthcare systems on redistribution of hub and spoke hospital networks for CV emergency and reorganization of ED and hospital paths are described in sections 7 and 8, respectively, the main principles of STEMI management in the COVID-19 pandemic are the following: Specific pathways for management of STEMI patients are illustrated in Figure 13. It is suggested to perform left ventriculography during catheterization of any ACS patients to reduce the need for echocardiography and shorten hospital stay. The treatment of the non-culprit lesions should be managed according to patients’ clinical stability as well as angiographic features of those lesions. In the presence of persistent symptomatic evidence of ischaemia, subocclusive stenoses, and/or angiographically unstable non-culprit lesions, PCI during the same hospitalization should be considered. Treatment of other lesions should be delayed, planning a new hospitalization after the peak of the outbreak. CS and OHCA are time-dependent diseases needing relevant resources and optimal trained systems and dedicated networks for optimal outcome. In general, treatment of CS and OHCA should follow current guidelines and current evidence.101,114,137,140,141 However, considering that in an overwhelmed critical care system stressed by the pandemic COVID-19 infection it will not be possible for all the patients to receive ICU treatment due to limited resources. This leads to difficult situations based also on the four widely recognized principles of medical ethics (beneficence, non-maleficence, respect for autonomy and equity) which are also crucial under conditions of resource scarcity. If resources available are insufficient to enable all patients to receive the ideally required treatment, then multiple groups have considered and recommend fundamental principles to be applied in accordance with the following rules of precedence: Triage strategies, based on current evidence and a previously established critical care triage protocol developed by working groups for use during a worldwide influenza pandemic,142 are summarised in Table 11 and Table 12. Specific recommendations are provided for patients with and without concomitant infection in Figure 14. Two scenarios will be considered: The infection should be suspected according to recently defined epidemiological and clinical criteria.143 HCP managing patients with CCS in geographical areas heavily affected by the COVID-19 pandemic should consider the following main points: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been identified as a potential risk factor for serious clinical presentation of SARS-CoV‑2 infection.144 Potential impact of chronic aspirin therapy has been questioned. However, at the low dose administered in CCS, aspirin has very limited anti inflammatory effect. Therefore, CCS patients should not withdraw aspirin for secondary prevention. Statin therapy has been variably associated with favourable outcomes in patients admitted with influenza or pneumonia.145,146 On the other side, patients with COVID-19 have been sometimes reported to develop severe rhabdomyolysis or increased liver enzymes.147 In these latter cases, it may be prudent to temporarily withhold statin therapy. For CCS patients treated with antihypertensive drugs please refer to section 9.7. Non-invasive testing in patients with CCS is tailored upon different clinical presentations.148 In regions with high rate of SARS-CoV‑2 infection, evaluation of asymptomatic CCS patients with non invasive testing should be postponed in order not to expose these patients to an unnecessary risk of infection or overload the health care systems. For symptomatic patients with suspected CAD and a pre-test probability of 5–15%, functional imaging for detection of myocardial ischaemia or CCTA are normally recommended as initial tests to diagnose CAD. In regions with critical situation and medical system overloaded by the COVID-19 pandemic, CAD screening even in symptomatic patients should probably be postponed in the majority of patients. Yet, if necessary, depending upon local availability and expertise, CTA should be preferred (section 7.4). However, the increased workload of CT departments should be acknowledged; they have been heavily disrupted by the high request of pulmonary CT for patients with COVID-19. In addition, feasibility/accuracy of CCTA might be hampered in patients with COVID-19 for the common occurrence of tachycardia and at times severe renal dysfunction. In case CCTA is not suitable (e.g. inability of heart rate control, etc.) or available, non-invasive testing should be postponed. Alternative imaging modalities should be discouraged during the acute pandemic phase unless severe ischaemia is suspected, to minimize the access of the patients to healthcare system (SPECT/PET) or to prevent a close contact between patients and personnel (stress echocardiography). For known CCS patients, clinical follow-up should be done mostly via tele-health (a dedicated telephone line should be made available to patients). Physicians could therefore address most of the patients’ concerns related to continuation or changes in medical therapy. Possible onset/recurrence of unstable symptoms should be estimated within the clinical history of the patient in order to weigh the need for hospitalization and diagnostic testing. Symptomatic patients with very high clinical likelihood of obstructive CAD are generally referred to ICA without prior non-invasive diagnostic testing.148 However, even in these patients, medical treatment should be attempted first in order to reserve ICA with possible ad-hoc revascularization only in case of clinical instability, especially in regions were healthcare systems are heavily overloaded by patients with COVID-19.149 Revascularization (either by PCI or coronary artery bypass graft [CABG]), can be postponed in most CCS patients. However, in hospitals whose ICUs are dedicated to or overloaded with high numbers of patients with COVID-19, the impact on CABG deferral might be even more pronounced. Priority is given to keep ICU beds available for COVID-19 patients requiring critical care. Therefore, healthcare systems might identify COVID-19-free hospitals serving as hubs for selected CCS patients in whom invasive and surgical procedures cannot be postponed. In these latter patients, SARS-CoV‑2 infection should be ruled out by nasopharyngeal swab/tracheobronchial aspiration and/or CT scan before hospital admission. Alternatively, in selected patients, hybrid revascularization CABG/PCI or even full-PCI can be considered by the heart team based on patient’s clinical conditions and local situation (see Table 13). Patients with CV comorbidities are at increased risk of the more severe presentation and complications of COVID-19. In a meta-analysis of 6 studies (n = 1527), hypertension and cardio/cerebrovascular diseases were present in 17.1%, and 16.4%, of hospitalized COVID-19 patients, respectively, and conferred ~2-fold and ~3-fold higher risk, respectively, for the more severe COVID-19.150 In 21 patients admitted to an ICU for severe COVID-19, 7 (33.3%) patients developed dilated cardiomyopathy, characterized by globally decreased LV systolic function, clinical signs of CS, elevated creatine kinase (CK), or troponin I levels, or hypoxaemia, without a past history of systolic dysfunction.89 An analysis of mortality causes in COVID-19 patients (150 hospitalized/68 dead) revealed that myocardial damage/HF and combined respiratory failure/myocardial damage/HF were responsible for 7% and 33% of fatal cases, respectively.66 There are several, not mutually exclusive, mechanisms of acute HF in COVID-19 such as: Incidence, underlying mechanisms and risk factors of SARS-CoV‑2-associated myocarditis are currently unclear. Recently, a high viral load has been reported in 4 patients who subsequently developed fulminant myocarditis.33 One published case involved a 38-year-old male presenting with chest pain, hypotension, bilateral pneumonia with pleural effusions and ST segment elevation, but with normal CT coronary angiogram.104 Echocardiography demonstrated dilatation and a marked decrease in LV ejection fraction (LVEF), and a 2 mm thick pericardial effusion. Troponin I and BNP levels were notably high. The patient successfully recovered after receiving high-dose parenteral glucocorticoid anti inflammatory therapy and immunoglobulin, along with other therapeutic measures. During the COVID-19 outbreak, patients with chronic HF should be advised to closely follow protective measures aimed at preventing disease transmission (e.g. self-isolation, social distancing, frequent hand washing, use of hand sanitizers and wearing a face mask in public spaces). Ambulatory stable HF patients (with no cardiac emergencies) should refrain from hospital visits. Routine clinical methods, ECG (arrhythmias, myocardial ischaemia, myocarditis) and chest X-ray (cardiomegaly, COVID-19 pneumonia) can provide a diagnostic clue. Due to the relatively low sensitivity of chest X-ray to detect COVID-19 pneumonia, patients with a high degree of clinical suspicion (tachypnoea, hypoxaemia), but with ambiguous chest X-ray findings, should be referred to chest CT.152 Laboratory findings, such as increased erythrocyte sedimentation rate, fibrinogen and C-reactive protein, and lymphocytopenia, may suggest COVID-19 pneumonia. TTE is very important, not only to evaluate pre-existing LV dysfunction in HF, but also to assess patients suspected of having SARS CoV 2-associated myocarditis.153 During all medical procedures, an attention should be given to prevent viral transmission to HCP. SARS-CoV‑2 utilizes the ACE2 receptors for cell entry and some data indicate that ACEIs and ARBs may upregulate ACE2,154 thus hypothetically increasing the susceptibility to the infection. Recently, a case series of 12 patients with COVID-19-associated ARDS, demonstrated that plasma Ang II levels were markedly elevated and linearly associated with viral load and lung injury.33 This has led to a suggestion that ARB treatment could have a beneficial effect in curbing the Ang II-mediated lung injury. Clearly, further research in required to resolve the controversies regarding the role of ACEI/ARB in COVID-19. There is currently no clinical evidence of an association between ACEI/ARB treatment and the susceptibility to infection, or the clinical course. Withdrawal of medical treatment in HF patients may increase the risk of worsening HF.155 Available data do not support discontinuation of ACEI/ARB and it could be recommended that HF patients continue guideline-directed medical therapy, including beta blockers, ACEI, ARB, or sacubitril/valsartan, and mineralocorticoid receptor antagonists, irrespective of COVID-19.156 COVID-19 patients may become hypotensive due to dehydration and haemodynamic deterioration, hence adjustment of medication doses should be considered. The more widespread use of telemedicine should be encouraged to minimize the risk of SARS-CoV‑2 transmission, in both HF patients, and HCP. Whenever possible, this technology should be utilized to provide medical advice and follow-up of stable HF patients, and to reserve direct patient provider contact for the emergency situations. It is advisable that HCP make a telephone contact with the ambulatory chronic HF patient to verify the need for the hospital visit, but also to provide psychological support. If feasible (and necessary), home delivery and mailing of standard HF drugs to the patients is a viable option. Due to the nature of the device, LVAD patients have an increase susceptibility to the infection, and every measure should be used to prevent viral transmission. Cautious monitoring and management of anticoagulation therapy is advised, because both COVID-19 and antiviral medications can affect anticoagulant dosing. If technically feasible, assessment of LVAD function by telemonitoring is preferable. General recommendations for all LVAD patients should be also applied, regardless of COVID-19. The susceptibility to the infection and the clinical course of COVID-19 in heart transplant recipients is not known. Recently, two cases (one mild, another more severe) of COVID-19 have been described in heart transplant recipients in China.159 Importantly, the presenting symptoms were similar to those of immunocompetent individuals, including fever, elevated inflammatory markers (e.g. C-reactive protein), lymphocytopenia and chest CT demonstrating bilateral ground-glass opacities. The treatment of the patient with more severe infection included temporary discontinuation of baseline immunosuppressant medications and institution of high-dose glucocorticoids, immunoglobulins and fluroquinolone antibiotics, along with other treatment measures. Of note, both patients recovered and remained rejection-free. Yet another report of 87 heart transplant recipients from China, indicated that high-degree adherence to preventive measures (see above), resulted in a low rate of possible infection and transition to manifest illness (e.g. 4 patients were reported to have airway tract infection and 3 of them had a negative SARS-CoV‑2 test result, whilst 1 patient was not tested).160 Importantly, all patients fully recovered after treatment. Although VHD has not been explicitly linked to increased morbidity and mortality in early COVID-19 case series, up to 40% of the patients admitted to the ICU had pre-existing congestive HF.89 VHD mainly affects the elderly and the symptoms of disease progression (mainly dyspnoea) may mimic those of lung infection or infiltration. In addition, VHD may aggravate the course of COVID-19 infection and complicate haemodynamic management of the systemic inflammatory response (cytokine storm),161 ARDS, and any superimposed bacterial septicaemia (observed in up to one third of ICU patients).65 Elective surgical and transcatheter interventions for VHD consume significant health care resources and many (or all, according to circumstances) may be inappropriate during the pandemic given the immense pressure on acute and intensive care facilities. However, patients with severe VHD must remain under close telephone surveillance and be encouraged to report progressive symptoms. Concentration of resources on the treatment of pandemic victims guides decisions with the overall aim of avoiding shortage of ICU beds and ventilators. Prioritization of valve interventions should therefore balance the immediate and short-term prognosis of individual patients against available resources and the risk to patients and HCP of acquiring in-hospital infection. In this respect, use of less invasive procedures (particularly transcatheter aortic valve implantation [TAVI] via transfemoral approach performed under conscious sedation and/or local anaesthesia), may present an opportunity to minimize ICU and hospital stay. The need for clinical decision making by Heart Teams remains of paramount importance and use of telemedicine (or other means of virtual communication) is essential if face-to-face meetings are difficult (or impossible) during the acute phase of the pandemic. The prognosis of patients with severe aortic stenosis (AS) depends on several factors, including age, symptomatic status, peak aortic jet velocity/mean transvalvular gradient,162,163 LVEF, pulmonary hypertension,164 and elevated biomarkers (natriuretic peptides or troponin).165-167 Mortality of patients with severe symptomatic AS who are treated conservatively is high, reaching 50% at 1 year and 70–80% at 2 years.168 Deferring surgical aortic valve replacement (SAVR) or TAVI by several months may therefore affect prognosis. In the context of the COVID-19 pandemic, the Heart Team should undertake systematic individual risk assessment based on objective criteria that determine disease progression. Priority should be given to patients with syncope or HF (New York Heart Association [NYHA] Class III/IV), high or very high transvalvular gradients and those with reduced LV function Table 8, whereas a watchful waiting strategy is more appropriate in those with minimal or no symptoms. TAVI (or balloon aortic valvuloplasty) may be considered in haemodynamically unstable patients (COVID-19 positive/negative). However, the potential benefits of valve intervention in a critically ill COVID-19 positive patient (no cases reported to date) should be carefully weighed against the likelihood of futility given the > 60% mortality of COVID-19 positive patients admitted to ICU.169 All cases should be discussed by the Heart Team and indications for TAVI extended to intermediate170,171 and selected low-risk patients.172,173 Increased use of transfemoral TAVI (when feasible) may allow optimal utilization of resources by avoiding general anaesthesia and intubation, shortening (or preventing) ICU stay and accelerating hospital discharge and recovery.174 The management of MR differs according to its aetiology and presentation. Chronic primary MR (flail leaflet and Barlow disease) is usually stable and well tolerated. In contrast, SMR is a more variable entity and whilst many patients remain stable under guideline directed medical and device treatment (including sacubitril/valsartan and cardiac resynchronization therapy when indicated),175 others may develop unstable HF syndromes that are refractory to medical treatment, particularly in the context of acute infection.176 In the context of the COVID-19 pandemic, priority should be given to the treatment of patients with acute primary MR complicating AMI or IE, and those with severe primary or SMR who remain symptomatic despite guideline-directed medical and device treatment and seem likely to require hospital admission. All other patients should be managed conservatively.175-178 Transcatheter mitral edge-to-edge repair may be considered in anatomically suitable high-risk or inoperable patients with acute MR (excluding those with IE) or highly selected patients with decompensated primary MR or SMR refractory to guideline-directed medical and device treatment. Despite a low risk of complications requiring ICU admission,179 the procedure requires general anaesthesia (in distinction to transfemoral TAVI) and prolonged echocardiographic guidance, thereby exposing interventionists and anaesthetists to the risk of COVID-19 transmission. Use of temporary circulatory support (intra-aortic balloon pump or Impella) should be restricted to patients with a good prospect for recovery in the context of available ICU resources. Initial reports from China noted that hypertension was one of the most common co-morbidities (20–30% of cases) associated with the need for ventilatory support due to severe respiratory complications of COVID-19 infection.10,65,80,99,180 These analyses did not adjust for age, which is important because hypertension is very common in older people (~50% in people aged over 60 years are hypertensive) and hypertension prevalence increases sharply in the very old. Older age is also the most important risk factor for severe complications and death due to COVID-19, thus, a high frequency of hypertension would be expected in older patients with severe infection because of their older age. Indeed, a higher frequency of hypertension would be expected in older COVID-19-infected patients, than has been reported. It now seems likely that the reported association between hypertension and risk of severe complications or death from COVID-19 infection is confounded by the lack of adjustment for age and other unmeasured confounders.47 There is currently no evidence to suggest that hypertension per se is an independent risk factor for severe complications or death from COVID-19 infection. RAS blockade with ACEIs or ARBs are the foundation of antihypertensive therapy in the current ESC-ESH Guidelines for the management of arterial hypertension (2018).181 The recommended treatment of hypertension for most patients is combinations of an ACEI or ARB with a calcium channel blocker (CCB) or thiazide/thiazide like diuretic.181 Concern has been expressed that treatment with ACEIs or ARBs might increase the risk of infection, or developing the severe consequences of infection with COVID-19.21,46,182 This concern originates from a hypothesis that links the observations that COVID-19 invades cells by binding to the enzyme ACE2 which is ubiquitous and expressed on the surface of alveolar cells in the lung.39,41,183 In some animal studies, but not all, ACEIs or ARBs have been shown to increase ACE2 levels mainly in cardiac tissue.49,184,185 Importantly, there have been no studies showing that RAS-blocking drugs increase ACE2 levels in human tissues and no studies in animals or humans showing that RAS-blocking drugs increase ACE2 levels in the lung, or that the level of ACE2 expression in the lung is rate limiting for COVID-19 infection. Moreover, there have been no studies in humans demonstrating an independent link between RAS blocker use and the development of severe complications of COVID-19 infection, after adjustment for age and other comorbidities. Recently a series of observational cohort studies have been published which consistently show that treatment with RAS blockers does not increase the risk of COVID-19 infection, or increase the risk of severe complications or death from COVID-19 infection.54-60 In one study, there was even a substantial reduction in risk of severe complications or death from COVID-19 infection in patients with diabetes mellitus.56 These recent findings are very important and provide reassurance to patients and their doctors that prior speculation about the safety of RAS blockers in the context of COVID-19 infection has not been proven. Indeed, studies in animal models of infection with influenza or coronaviruses have suggested that ACE2 is important in protecting the lung against severe injury and that RAS-blocking drugs are also protective against severe lung injury due to these viruses.186-188 Human studies of RAS-blockade or recombinant ACE2 to prevent respiratory decompensation in COVID-19 infected patients have been suggested, planned or are ongoing.189,190 In summary, there is currently no evidence to suggest that ACEIs or ARBs increase the risk associated with COVID-19 infection and there is no reason why these drugs should be discontinued due to concern about COVID-19 infection. Treatment of hypertension when indicated, should continue to follow the existing ESC-ESH guideline recommendations.191 Most patients with hypertension require only infrequent visits to the clinic to manage their hypertension. Many patients with treated hypertension will be in self isolation to reduce the risk of COVID-19 infection and unable to attend for their usual routine clinical review. When possible, patients should monitor their own BP as frequently as they usually would, using a validated home BP monitor.181 Videoconference or telephone consultation with patients when required may facilitate urgent physician follow up until normal clinic attendance resumes. Most patients who are hospitalized, will have more severe infection and be hospitalized for respiratory support. They are likely to be older with comorbidities such as hypertension, diabetes and chronic kidney disease. Patients with severe disease may also develop multi-organ complications in severe disease. Hypertensive patients may also have LV hypertrophy or heart disease and be at increased risk of developing arrhythmias, particularly when hypoxic.192 Plasma potassium levels should be monitored because arrhythmias may be exacerbated by the frequent occurrence of low plasma potassium levels or hypokalaemia that was first noted in SARS coronavirus infection193 and early reports suggests is also prominent in hospitalized COVID-19-infected patients.194 This is thought to be due to increased urinary loss of potassium, which may be exacerbated by diuretic therapy. If patients are acutely unwell and become hypotensive or develop acute kidney injury due to their severe disease, antihypertensive therapy may need to be withdrawn. Conversely, parenteral antihypertensive drugs are rarely but sometimes needed for hypertensive patients who are ventilated and have sustained and significant increases in BP after withdrawal of their usual treatment (i.e. grade 2 hypertension, BP > 160/100 mmHg) but the objective in these acute situations is to maintain BP below these levels and not aim for optimal BP control. Although solid evidence is unavailable to date, a number of case reports suggest that the incidence of PE in patients with COVID-19 infection may be high.195-197 Taking this into account, together with COVID-19-associated systemic inflammation, coagulation activation, hypoxaemia and immobilization, anticoagulation at standard prophylactic doses should be considered for all patients admitted to the hospital with COVID-19 infection. Patients with COVID-19 infection often present with respiratory symptoms and may also report chest pain and haemoptysis.80 These symptoms largely overlap with the presentation of acute PE which may cause underdiagnosis of this relevant complication.198 Unexpected respiratory worsening, new/unexplained tachycardia, a fall in BP not attributable to tachyarrhythmia, hypovolaemia or sepsis, (new-onset) ECG changes suggestive of PE, and signs of deep vein thrombosis of the extremities should trigger a suspicion of PE. It is recommended to only order diagnostic tests for PE when it is clinically suspected, although it is recommended to keep a low threshold of suspicion. The specificity of D-dimer tests may be lower in patients with COVID-19 compared to other clinical settings. Even so, it is still advised to follow diagnostic algorithms starting with pre-test probability and D-dimer testing, especially when pre-test probability dependent D-dimer thresholds are being used.120-122 This may help to rationalize the deployment of resources and personnel for transporting a patient to the radiology department with all the associated isolation precautions. In the clinical scenario of a patient with COVID-19, who has just undergone CT of the lungs but the findings cannot explain the severity of respiratory failure, CT pulmonary angiography may [or should] be considered before leaving the radiology department. When acute PE is confirmed, treatment should be guided by risk stratification in accordance with the current ESC guidelines.119 Patients in shock should receive immediate reperfusion therapy. Haemodynamically stable patients may be treated with either unfractionated heparin (UFH), low molecular weight heparin (LMWH) or a NOAC, depending on the possibility of oral treatment, renal function and other circumstances. When choosing the appropriate drug and regimen (parenteral versus oral) for initial, in-hospital anticoagulation, the possibility of rapid cardiorespiratory deterioration due to COVID-19 should be taken into account. Of note, some of the investigational drugs for COVID-19 may have relevant interactions with NOACs. In particular, this may be the case for lopinavir/ritonavir via Cytochrome P450 3A4 (CYP3A4) and/or P-glycoprotein (P-gp) inhibition. In such cases, the bleeding risk may be elevated and NOACs should be avoided. Because close monitoring is necessary which may contribute to spreading of the infection, vitamin K antagonists (VKAs) should only be considered in special circumstances such as the presence of mechanical prosthetic valves or the antiphospholipid syndrome.119 Very few data are available on antiarrhythmic management specifically in COVID-19 patients. Therefore, this text reflects a consensus based on limited evidence. This text will be updated if more information becomes available. The general principles of management of patients with cardiac arrhythmias and cardiac implantable devices during the COVID-19 pandemic are based on: Several national societies and health services including the Heart Rhythm Society, National Health Service (UK) and the Cardiac Society of Australia and New Zealand have issued similar local recommendations to achieve these goals and guide the management of patients with cardiac arrhythmias and cardiac implantable devices during the COVID-19 pandemic.199-201 Below, we review considerations for implantable cardiac device monitoring and follow-up, elective and urgent EP procedures and treatment options of cardiac arrhythmias during the COVID-19 pandemic. Urgent in-hospital or ambulatory device interrogations may be needed for patients with suspected new and severe lead dysfunction; battery depletion especially in PM-dependent patients; malignant arrhythmia detection; appropriate or inappropriate ICD therapy delivery if this cannot be sufficiently managed by remote interrogation/monitoring; The categorization of EP procedures in the context of COVID-19 is depicted in Table 14. In summary, all elective ablation and cardiac device implantation procedures should be postponed, and antiarrhythmic medications should be reviewed and intensified if necessary, to allow control of symptomatic arrhythmia recurrences during the COVID-19 pandemic period. Urgent EP procedures in patients without suspected or confirmed COVID-19 infection should be performed in a designated non-infected catheterization laboratory area, while limiting direct contact with personnel, and with the appropriate use of PPE (Section 5) during the procedure. In patients with suspected or confirmed COVID-19 infection, the procedure should be performed in a designated catheterization laboratory area, while limiting direct contact with personnel, and with the appropriate use of PPE (Section 5) during the procedure. If intubation is required, this should be performed outside the EP laboratory to avoid contamination. The hospital stay and all ancillary procedures (ECG, echocardiography) should be reduced to minimum and be performed after clinical reassessment of their necessity. The incidence and type of cardiac arrhythmias as a direct consequence of COVID-19 infection is currently unknown. In a single centre retrospective study including 138 patients hospitalized with COVID-19 pulmonary infection in Wuhan, China, cardiac arrhythmias occurred in 23 patients (16.7%) and acute cardiac injury in 10 (7.2%) patients (defined as troponin rise, or new ECG and echocardiographic abnormalities). Cardiac arrhythmias were considered a major complication and occurred more frequently in patients who were transferred to the ICU as opposed to the patients treated on the general ward (16 [44%] of 36 patients vs. 7 [6.9%] of 102 patients, p < 0.001, respectively).10 However, the type and duration of arrhythmias was not specified in this report. In general, the acute treatment of arrhythmias should not be significantly different from their management in non-COVID-19 patients and should be in line with the current ESC, European Heart Rhythm Association and related guidelines.202-208 126.96.36.199.1. Supraventricular Tachycardia There are no specific reports on the incidence of non-AF/atrial flutter type of paroxysmal supraventricular tachycardia (PSVT) during COVID-19 infection. In theory, exacerbation of known PSVT or new-onset PSVT may occur in patients with COVID-19 infection. Special considerations during the COVID-19 pandemic are the transient unavailability of catheter ablation procedures for definitive treatment, the risk of nosocomial infection during repeated ED visits, and the possibility of therapy interactions with AADs (see Section 10). 188.8.131.52.2. Atrial Fibrillation and Flutter There are no specific reports on the occurrence of AF during COVID-19 infection. It is likely that AF may be triggered by COVID-19 infection (fever, hypoxia, adrenergic tone), either new onset or recurrent. In patients with severe pneumonia, ARDS and sepsis, the incidence of AF during hospitalization is known to be high. Reportedly 23–33% of critically ill patients with sepsis or ARDS had AF recurrence and 10% developed new-onset AF.202,209-211 New-onset AF in sepsis and ARDS has been associated with higher short- and long-term mortality, very high long-term recurrence rate and increased risk of HF and stroke.202,209-211 In a recent report from Italy, among 355 COVID-19 patients who died (mean age 79.5 years, 30% women), retrospective chart review identified a history of AF in 24.5%.18 This finding supports the estimates that especially older patients admitted to the hospital (and ICU) with COVID-19 associated pneumonia, ARDS and sepsis frequently develop new-onset or recurrent AF, which may further complicate management. Specific precipitating factors in this setting are hypokalaemia and hypomagnesaemia (induced by nausea, anorexia, diarrhoea and medications), metabolic acidosis, the use of inotropic agents (especially dobutamine and dopamine), ventilator dyssynchrony, volume overload, increased sympathetic tone, inflammation, hypoxia, ischaemia, bacterial superinfection and myocardial injury.202 As in all patients with AF, treatment goals have to consider ventricular rate control, rhythm control and thromboembolic prophylaxis. Specifically in the context of COVID-19 infection, the following considerations should be made (Figure 16): 184.108.40.206.3. Ventricular Arrhythmias Although there are no reports on the incidence of ventricular arrhythmias in the general population of patients with COVID-19 infection, a recent single centre retrospective study from Wuhan analyzed the occurrence and significance of malignant ventricular arrythmias in 187 hospitalized patients with confirmed COVID-19 infection. Among the 187 patients (mean age 58 ±14.7 years, 49% male), 43 (23%) patients died during hospitalization. Overall, 66 (35.3%) patients had underlying CVD including hypertension (32.6%), coronary heart disease (11.2%), and cardiomyopathy (4.3%), and 52 (27.8%) patients exhibited myocardial injury as indicated by elevated Troponin T levels. During hospitalization, malignant ventricular arrhythmias (defined as sustained VT or VF) occurred in 11 (5.9%) patients. VT/VF occurred more frequently in patients with elevated troponin levels (17.3% vs. 1.5%, p < 0.001).25 These findings suggest that new-onset malignant ventricular arrhythmia is a marker of acute myocardial injury and may warrant more aggressive immunosuppressive and antiviral treatment. In patients with a history of CVD and ventricular arrhythmias, exacerbation of the known VT/VF may occur due to COVID-19 infection as trigger. Although reports are not available for COVID-19, a correlation between increased appropriate ICD therapies and influenza epidemic has been shown.212 Special considerations during the COVID-19 pandemic are depicted in Figure 17 and summarized below: There are no specific reports on the occurrence of COVID-19 infection in patients with channelopathies. However, COVID-19 infection may occur in patients with known congenital LQTS, Brugada syndrome (BS), catecholaminergic polymorphic ventricular tachycardia (CPVT) and short QT syndrome, with a risk of pro-arrhythmia. The specific interactions of these channelopathies and COVID-19 has been reviewed in a recent review.213 In theory, exacerbation of known conduction system or sinus node disease or new-onset high degree AV block or sinus node dysfunction may occur in patients with COVID-19 infection, especially in case of myocardial involvement. Other mechanisms of AV block in COVID-19 are vagally mediated due to neuroinvasion, or hypoxia. A case of transient AV block in a critical COVID patient was recently published.215 One experimental study from 1999 has shown that coronavirus-infected rabbits have ECG abnormalities including 2nd degree AV block secondary to myocarditis and HF.212 In critically ill patients in the ICU, transient bradycardia and asystole may occur due to patient turning for prone respiration, intubation, or trachea suction and is probably due to transient increased vagal tone.202 Hypoxaemia should be ruled out. A heart rate/temperature discordance was observed in patients with COVID-19:10,102 The heart rate at admission was about 80 beats per minute (bpm), slower than expected in these patients with fever. This has also been observed in other infectious disease such as typhoid fever. Special considerations for permanent PM implantation in patients with COVID-19 are the poor prognosis of patients requiring mechanical ventilation, increased risk of bacterial superinfection and device infection in the critically ill patients, risk of nosocomial infection during device implantation in COVID-19 negative patients (see above) and transient bradyarrhythmic side effects of antiviral therapy. Treatment strategies against SARS-CoV‑2 potentially use a combination of several drugs exerting synergistic effects. Despite the lack of definitive evidence on their efficacy, drugs with suspected viricide effect that are being used ‘off-label’ include chloroquine/hydroxychloroquine, protease inhibitors (like lopinavir-ritonavir or, in a minority of cases, darunavir-cobicistat), remdesivir and azithromycin.217-220 In specific cases, interferon and, for the ARDS glucocorticoids and/or tocilizumab, may also be administered.221 Chloroquine has been widely used as an antimalarial drug and in the treatment of rheumatological diseases like systemic lupus erythematosus and rheumatoid arthritis, and has been found to inhibit SARS-CoV‑2 growth in vitro.218-220 Hydroxychloroquine is an analogue of chloroquine with less gastric intolerance and less concerns for drug interactions. In vitro, hydroxychloroquine was found to be more potent than chloroquine in inhibiting SARS-CoV‑2.220 A recent small clinical study reported that SARS-CoV‑2 positivity in nasopharyngeal secretions is significantly decreased at day 6 after inclusion (i.e. day 10 after symptom onset) in hydroxychloroquine-treated COVID-19 patients (n = 26) versus patients who received supportive care only (n = 16). However, several major limitations (small sample size; non-homogeneous groups with differences in viral loads, number of days since onset of symptoms and quality of follow-up; and rather late administration of the drug, close to the expected time of viral clearance), raise doubts about the significance of the findings.218 The current evidence therefore does not imply yet a translation of (hydroxy)chloroquine in vitro activity to clinically relevant outcomes. Results of ongoing clinical trials of chloroquine/hydroxychloroquine efficacy in the treatment of SARS-CoV‑2 should be awaited before definite recommendations are provided for or against the use of these drugs. One major concern with these drugs is the very rare risk of QTc prolongation and TdP/sudden death. A recent metanalysis on arrhythmogenic cardiotoxicity of the quinolines and structurally related antimalarial drugs suggested that this risk is minimal (no events of SCD or documented VF of TdP in 35 448 individuals, 1207 of whom were taking chloroquine).222 However, during COVID-19 infection, the QT-related risk may be amplified by concomitant use of other QTc-prolonging drugs and/or electrolyte imbalances (hypokalaemia, hypomagnesaemia and/or hypocalcaemia). A second concern with chloroquine/hydroxychloroquine is the potential occurrence of conduction disturbances, although these are rare and appear to be linked mostly to long-term treatment (Table 15). The protease inhibitor lopinavir-ritonavir has shown to be effective against SARS-coronavirus and MERS-coronavirus in vitro and in animal models.223-226 A recent randomized controlled open-label trial suggested that in hospitalized patients with severe COVID-19, lopinavir-ritonavir combined therapy does not provide additional benefit to standard of care.227 The main criticism of this study is the delayed time from illness onset to treatment assignment (median 13 days). Importantly, no pro-arrhythmic major adverse events were described in either arm and there was only one QTc prolongation in the lopinavir ritonavir arm (no details on the degree or the existence of other concomitant QTc prolonging factors).227 However, important drug-drug interactions have been described (mainly because these potent CYP3A4 inhibitors interfere with (hydroxy)chloroquine metabolism) that should be taken into consideration. In some combinations, dose adjustments or changes may be needed (Table 15). When lopinavir-ritonavir is not available and/or the patient is intolerant, darunavir-cobicistat is used as an alternative. In vitro and animal studies suggest that remdesivir (GS-5734) is effective against zoonotic and epidemic SARS-coronavirus and MERS-coronavirus.228-230 Several randomized controlled studies are underway in the current SARS-CoV‑2 epidemic. In vitro studies suggest a better efficacy of remdesivir compared to lopinavir-ritonavir.230 An advantage of remdesivir is that no significant drug interactions have been described. However, there are no reports on its effect on QTc duration. Unfortunately, currently it is not widely available worldwide (only in clinical trials or for compassionate use from Gilead Sciences, Inc.). The anecdotal evidence supporting the use of azithromycin (being a weak CYP3A4 inhibitor) comes from the above-mentioned open-label small non-randomized study of hydroxychloroquine treated COVID-19 patients (n = 26) versus patients who received supportive care only (n = 16). In 6 patients, the addition of azithromycin to hydroxychloroquine showed significant SARS-CoV‑2 positivity reduction in nasopharyngeal secretions compared to hydroxychloroquine alone.218 Azithromycin has in isolated cases been associated with QTc prolongation and TdP mainly in individuals with additional risk factors.231,232 Two studies have evaluated the association of chloroquine and azithromycin for the prevention and treatment for malaria in Africa with 114 and 1445 individuals, respectively in the arm treated with the combination.233,234 The association of chloroquine and azithromycin showed an acceptable safety profile. For a detailed overview of all known direct or indirect (through drug-drug interactions) arrhythmological effects of experimental pharmacological therapies in COVID-19 patients, see Table 15. QTc prolongation by some drugs can theoretically lead to polymorphic VT (TdP). This is however a very rare complication, and the consideration has to be balanced versus the anticipated benefit of therapy for the COVID-19 patient. Figure 19 provides a practical flow chart for the management of patients to prevent TdP, for guidance on the timing and repetition of ECG recording, and on QTc measurements that would alter therapy. Other guidance flowcharts have been published.213, 262 Briefly, the following steps are required to reduce the risk of drug induced TdP: Bradycardia prolongs QT and facilitates TdP. While some COVID-19 drugs have a weak bradycardic effect, the concomitant use of beta-blockers, CCBs, ivabradine and digoxin should also be evaluated. If digoxin is considered mandatory for the patient, plasma level monitoring should be considered (with ensuing dose reduction if needed). For patients with wide QRS complex (≥ 120 ms) due to bundle branch block or ventricular pacing, QTc adjustment is needed. Formulae are available, but a simpler approach may be to use a QTc cut off of 550 ms instead of 500 ms. Others propose a rule of thumb to calculate QT minus (QRS width 100 ms). A standard 12-lead ECG may not always be easy to obtain, given the enormous burden of increasing numbers of COVID-19 patients on healthcare providers. Enhanced use of modern handheld ECG devices should be considered in order to reduce traditional ECG recording as much as possible to preserve resources and limit virus spread. In a recent study, the QTc in lead‐I and lead‐II derived from a standard 12-lead ECG was compared with a rhythm strip from a handheld ECG device in 99 healthy volunteers and 20 hospitalized patients in sinus rhythm treated with dofetilide or sotalol.264 QT on the handheld device had an excellent agreement with standard 12‐lead ECG both in the normal range and in patients with QT prolongation.264 This handheld ECG device (KardiaMobile 6L Alivecor) had a high specificity for detecting a QTc > 450 ms and should thus be considered as an effective outpatient tool for monitoring patients with prolonged QTc. Recently, KardiaMobile6L received expedited approval from the FDA for QT monitoring and can thus be used in COVID-19 patients treated with QT prolonging drugs such as chloroquine or hydroxychloroquine. Many cardiac patients or patients with other CV history will have an indication for anticoagulation. Table 16 lists the possible interactions of COVID-19 therapies with VKAs, NOACs, LMWHs and UFH. The table includes information that was derived from several drug interaction sites, which have been referenced. Drug SmPCs often do not contain information for older drugs and/or drugs with a narrow spectrum of indications (like chloroquine). Antimalarial drugs have a P-glycoprotein inhibiting effect, which may affect NOAC plasma levels. COVID-19 patients on oral anticoagulation may be switched over to parenteral anticoagulation with LMWH and UFH when admitted to an ICU with a severe clinical presentation. We would like to rephrase here also the conventional dose reduction criteria for NOACs, for those patients in whom oral treatment for stroke prevention in AF patients, can be continued. For more details, including the assessment of renal (and liver) function and other considerations in patients taking a NOAC, please see the 2018 EHRA Practical Guide on the use of NOACs in patients with AF.265 Of note, none of the NOACs is recommended in patients with a creatinine clearance (CrCl) <15 ml/min according to the EU label. For patients with impaired swallowing, NOACs can be administered in the following ways: There are many pending questions about the COVID-19 pandemic.274 What is the full spectrum of disease severity? How is the transmissibility? What is the role of asymptomatic/pre-symptomatic infected persons? How long is the virus present? What are the risk factors for severe illness? Knowledge is being accumulated very fast and our task is to deliver key information for patients with CVD. There are several clinical features associated worse short-term outcome of SARS-CoV‑2 manifestations.54 These include asthma, age > 65-year-old, COPD, chronic HF, cardiac arrythmias, coronary artery disease. Female sex, statin therapy or ACE inhibitors appear to be independent protective factors. The effect of social background and ethnicity on survival needs some clarification. A cause-and-effect relationship between drug therapy and survival should not be inferred given the lack of ongoing randomized trials. Patients should be informed and take appropriate precautions with emphasis on measures for social distancing when the potential risk is high and medical resources are scarce. The following information is important for individuals with CVD: Additionally, individuals should be encouraged to follow the instruction of the Department of Health and local authorities in the resident countries as these may differ. Maintain a healthy lifestyle (e.g. eat healthy, quit smoking, restrict alcohol intake, get adequate sleep and keep physically active).276 Isolation and physical restrictions may lead to inactivity and increased risk of VTE, in combination with co-morbidities. Physical activity should be strongly encouraged either in a home setting or outdoor areas with social space and will also improve well-being. Maintaining social network should be encouraged remotely. Figure 1 Cumulative laboratory-confirmed cases of COVID-19 in Europe (World Health Organization) Figure 2 Critical role of ACE2 in the regulation of viral invasion in ACE2 expressing cells (Created using BioRender Academic). Figure 3 Cardiovascular involvement in COVID-19 – key manifestations and hypothetical mechanisms. Figure 4 Different types of masks to be used according to type of procedures and levels of risk. Figure 5 Guidance on donning personal protective equipment (PPE) to manage COVID-19 patients (modified from the "Handbook of COVID-19 Prevention and Treatment").77 Figure 6 Guidance on removing personal protective equipment (PPE) to manage COVID-19 patients (modified from the "Handbook of COVID-19 Prevention and Treatment").77 Figure 7 How do I protect myself? Figure 8 Algorithm for triaging patients admitted to the ER for a suspected acute CV disease Figure 9 Considerations in patients with suspected (or at risk for) cardiogenic shock and possible COVID-19 infection Figure 10 Temporal changes in high-sensitivity cardiac troponin I concentrations from illness onset in patients hospitalized with COVID-19. Differences between survivors and non-survivors were significant for all time points shown. ULN denotes upper limit of normal (adapted from Zhou et al.34) Figure 11 High-sensitivity cardiac troponin (hs-cTn) T/I concentrations should be interpreted as quantitative variables. Figure 12 Recommendations for management of patients with NSTE-ACS in the context of COVID-19 outbreak Figure 13 Management of patients with STEMI during COVID-19 pandemic Figure 14 Management of patients with cardiogenic shock (CS)/out-of-hospital cardiac arrest (OHCA) during COVID-19 pandemic Figure 15 Hypertension management in the COVID-19 context Figure 16 Atrial tachyarrhythmias Figure 17 Ventricular tachyarrhythmias Figure 18 Channelopathies Figure 19 QTc management Figure 20 Patient information during the COVID-19 pandemic Part 1 Figure 21 Patient information during the COVID-19 pandemic Part 2 Table 1 Types of diagnostic approaches in COVID-1954, 65; *-still in experimental phase, now available for research; POC – point of care Table 2 Testing priorities for COVID-19 pandemic according to Center for Disease Control, US Table 3 General recommendations for Health Care Personnel, with adaption differentiated according to local community level of risk and containment strategies Table 4 Patient risk status73 Table 5 SARS-CoV‑2 related personal protection management73, 81 Table 6 Non-invasive cardiovascular stress testing and imaging tests with the potential for deferral in the light of the COVID pandemic (Reproduced from Gluckman127) Table 7 Impact on the healthcare system and regional involvement in the epidemic Table 8 Strategical categorization of invasive cardiac procedures during the COVID-19 outbreak Table 9 Recommendations for fibrinolytic therapy (Extracted from 114) Table 10 Doses of fibrinolytic agents and antithrombotic co-therapies (Extracted from 114) Table 11 Detailed inclusion and exclusion criteria for triage in intensive care unit upon admission (modified from Christian et al)142 Table 12 Criteria for little or no likelihood of benefit with ICU treatment (occurrence of at least 1 criterion) Table 13 Management of chronic coronary syndromes during COVID-19 pandemic Table 14 Categorization of electrophysiological procedures in the context of COVID-19 Table 15 Arrhythmological considerations of novel experimental pharmacological therapies in COVID-19 infection Table 16 Interactions of anticoagulant drugs with COVID-19 therapies Table 17 Concomitant conditions that may be associated with more severe course of SARS-CoV‑2 infection. Many of these features are confounded by age Table 18 Potential interactions of drugs used to cure COVID-19 The European Society for Cardiology. ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic. https://www.escardio.org/Education/COVID-19-and-Cardiology/ESC-COVID-19-Guidance. (Last update: 10 June 2020). The document is not a guideline. The recommendations are the result of observations and personal experience from health care providers at the forefront of the COVID-19 pandemic. © The European Society of Cardiology 2020. All rights reserved. Our mission: To reduce the burden of cardiovascular disease. © 2020 European Society of Cardiology. All rights reserved.	2	64	0	0	0	1	0.526978	1	24,264
A brain disease characterised by more than one cognitive disorder (e.g. reduced memory, mental capacity or recognition of objects or faces). Without further specifications, the diagnosis is demential syndrome (ICD-10 code: F03), which accounted for nearlyy 65 percent of dementia-related deaths in 2014 and is classified under mental disorders (Chapter F of the ICD-10 Codes). Alzheimer’s disease (ICD-10 code G30) is the most common form of dementia accounting for around 25 percent of dementia-related deaths in 2014, followed by vascular dementia (ICD-10 code F01), which accounted for around 9 percent of dementia-related deaths in 2014. For the purpose of tabulation of dementia as a cause of death, the ICD-10 codes F01-F03, F05 and G30 are combined together. This is because on death certificates, the term used to specify cause of death is often just dementia rather than the specific form; in addition, more mixed forms of dementia have been observed over time, e.g. vascular dementia combined with Alzheimer’s. The proportion of Alzheimer’s in dementia-related deaths went up from 10 to 25 percent over the period 1996-2014. The codes used cover around 90 to 95 percent of dementia-related deaths. A small proportion of dementia-related mortality is classified under ICD-10 code G31 (other degenerative diseases of the nervous system) without further distinction from other diseases of the nervous system, while a major part of the mortality caused by a fall (ICD-10 codes W00-W19) among people above 85 is caused by a decreased range of posture or motion which is related to dementia (in particular to lewy body dementia). Back to article	4	8	0	0	0	8	0.750046	8	362
Fibrocystic breast changes \|Fibrocystic breast changes\| \|Other names\|\|Fibrocystic change, fibrocystic breast disease, fibrocystic breast condition\| \|Micrograph showing fibrocystic breast changes. H&E stain.\| \|Symptoms\|\|Breast pain, breast cysts, breast masses\| \|Usual onset\|\|30 to 50 years old\| \|Risk factors\|\|Early age at first menstrual period, having children late or not having children\| \|Diagnostic method\|\|Periodic examination, possibly medical imaging or breast biopsy\| \|Differential diagnosis\|\|Breast cancer\| \|Treatment\|\|Education about the condition, a well fitting bra, pain medication\| \|Frequency\|\|Up to 60% of women\| Fibrocystic breast changes is a condition of the breasts where there may be pain, breast cysts, and breast masses. The breasts may be described as "lumpy" or "doughy". Symptoms may worsen during certain parts of the menstrual cycle. It is not associated with cancer. Risk factors include an early age at first menstrual period and either having children late or not having children. It is not a disease but represents normal breast changes. Diagnosis typically involves ruling out breast cancer. Fibrocystic change includes fibroadenomas, fibrosis, and papillomas of the breast. Management may involve education about the condition, a well fitting bra, and pain medication. Occasionally danazol or tamoxifen may be used for pain. It is estimated that up to 60% of women are affected. Women between the ages of 30 and 50 are most commonly affected. Signs and symptoms The changes in fibrocystic breast disease are characterised by the appearance of fibrous tissue and a lumpy, cobblestone texture in the breasts. These lumps are smooth with defined edges, and are usually free-moving in regard to adjacent structures. The lumps can sometimes be obscured by irregularities in the breast that are associated with the condition. The lumps are most often found in the upper, outer sections of the breast (nearest to the armpit), but can be found throughout the breast. Women with fibrocystic changes may experience a persistent or intermittent breast aching or breast tenderness related to periodic swelling. Breasts and nipples may be tender or itchy. Symptoms follow a periodic trend tied closely to the menstrual cycle. Symptoms tend to peak in the days and, in severe cases, weeks before each period and decrease afterwards. At peak, breasts may feel full, heavy, swollen, and tender to the touch. No complications related to breastfeeding have been found. The exact mechanism of the condition is not fully understood, though it is known to be tied to hormone levels, as the condition usually subsides after menopause and is also related to the menstrual cycle. Post-menopausal women placed on hormone replacement therapy have also reported symptoms of fibrocystic breast change indicating hormones may play a role. Fibrocystic breast changes is a cumulative process, caused partly by the normal hormonal variation during a woman's monthly cycle. The most important of these hormones are estrogen, progesterone and prolactin. These hormones directly affect the breast tissues by causing cells to grow and multiply. Many other hormones such as TSH, insulin, growth hormone and growth factors such as TGF-beta exert direct and indirect effects amplifying or regulating cell growth. Years of such fluctuations eventually produce small cysts and/or areas of dense or fibrotic tissue. Multiple small cysts and an increasing level of breast pain commonly develop when a woman hits her 30s. Larger cysts usually do not occur until after the age of 35. Over time, presumably driven by aberrant growth signals, such lesions may accumulate epigenetic, genetic and karyotypic changes such as modified expression of hormone receptors and loss of heterozygosity. Several variants of fibrocystic breast changes may be distinguished and these may have different causes and genetic predispositions. Adenosis involves abnormal count and density of lobular units, while other lesions appear to stem mainly from ductal epithelial origins. Diagnosis is mostly done based on symptoms after exclusion of breast cancer. Nipple fluid aspiration can be used to classify cyst type (and to some extent improve breast cancer risk prediction) but it is rarely used in practice. Biopsy or fine needle aspiration are rarely warranted. Fibrocystic breast disease is primarily diagnosed based on the symptoms, clinical breast exam and on a physical exam. During this examination, the doctor checks for unusual areas in the breasts, both visually and manually. Also, the lymph nodes in the axilla area and lower neck are examined. A complete and accurate medical history is also helpful in diagnosing this condition. If the patient's medical history and physical exam findings are consistent with normal breast changes, no additional tests are considered but otherwise the patient will be asked to return a few weeks later for reassessment. Women may detect lumps in their breasts during self-examination as well. In order to establish whether the lump is a cyst or not, several imaging tests may be performed. Mammography is usually the first imaging test to be ordered when unusual breast changes have been detected during a physical examination. A diagnostic mammography consists in a series of X-rays that provide clear images of specific areas of the breast. Ultrasounds and MRIs are commonly performed in conjunction with mammographies as they produce clear images of the breast and clearly distinguish between fluid-filled breast cysts and solid masses. The ultrasound and MRI exams can better evaluate dense tissue of the breast; hence it is often undergone by young patients, under 30 years old. The breast biopsy is usually the test used to confirm the suspected diagnosing. After imaging tests have been performed and have revealed unusual areas or lumps in the breast, a breast biopsy will be ordered. This test consists in removing a sample of breast tissue which is then looked at under a microscope. The specialist analyzing the tissue sample will be able to conclude if the breast changes are benign or malignant or whether breast fibrocystic disease is present. There are four main types of breast biopsies that may be performed. A fine-needle aspiration biopsy is usually ordered when the doctor is almost certain that the lump is a cyst. This test is generally performed in conjunction with an ultrasound which is helpful in guiding the needle into a small or hard to find lump. The procedure is painless and it consists in inserting a thin needle into the breast tissue while the lump is palpated. The core-needle biopsy is normally performed under local anesthesia and in a physician's office. The needle used in this procedure is slightly larger than the one used for a fine-needle biopsy because the procedure is intended to remove a small cylinder of tissue that will be sent to the laboratory for further examination. A newer type of breast biopsy is the stereotactic biopsy that relies on a three-dimensional X-ray to guide the needle biopsy of non-palpable mass. The biopsy is performed in a similar manner, by using a needle to remove tissue sample but locating the specific area of the breast is done by X-raying the breast by two different angles. Surgical biopsy is a procedure performed to remove the entire lump or a part of it for laboratory analyzing. It may be painful and is done under local anesthesia. Most women with fibrocystic changes and no symptoms do not need treatment, but closer follow-up may be advised. There is no widely accepted treatment or prevention strategy for fibrocystic condition. When treatment of symptoms is necessary it follows the same strategies as treatment for cyclical breast pain. A few small-scale studies have indicated that the fibrocystic condition may be improved by dietary changes (especially by a reduced intake of caffeine and related methylxanthines or by a reduced intake of salt) and by vitamin supplements. There are usually no adverse side effects to this condition. In almost all cases it subsides after menopause. A possible complication arises through the fact that cancerous tumors may be more difficult to detect in women with fibrocystic changes. Breast cancer risk Breast cancer risk is elevated for defined fraction of lesions. Except for people with a strong family history of breast cancer, where the risk is two-fold, nonproliferative lesions have no increased risk. Proliferative lesions also have approximately a 2-fold risk. In particular, atypical hyperplasia is associated with an increased risk of developing breast cancer. Atypical lobular hyperplasia is associated with the greatest risk, approximately 5-fold and especially high relative risk of developing premenopausal breast cancer. Atypical ductal hyperplasia is associated with 2.4-fold risk. In contrast, a New England Journal of Medicine article states that for women with a strong familial history of breast cancer, the risk of future breast cancer is roughly doubled, independent of histological status. The article further states "The relative risk of breast cancer for the cohort was 1.56 (95 percent confidence interval, 1.45 to 1.68), and this increased risk persisted for at least 25 years after biopsy. The relative risk associated with atypia was 4.24 (95 percent confidence interval, 3.26 to 5.41), as compared with a relative risk of 1.88 (95 percent confidence interval, 1.66 to 2.12) for proliferative changes without atypia and of 1.27 (95 percent confidence interval, 1.15 to 1.41) for nonproliferative lesions. The strength of the family history of breast cancer, available for 4808 women, was a risk factor that was independent of histologic findings. No increased risk was found among women with no family history and nonproliferative findings. In the first 10 years after the initial biopsy, an excess of cancers occurred in the same breast, especially in women with atypia." It is not well understood whether the lesions are precursors of breast cancer or only indication of increased risk, for most types of lesions the chance of developing breast cancer is nearly the same in the affected and unaffected breast (side) indicating only coincidence of risk factors. For atypical lobular hyperplasia there is high incidence of ipsilateral breast cancers indicating a possible direct carcinogenetic link. The estimated figures for the prevalence of fibrocystic breast changes in women over lifetime vary widely in the literature, with estimates ranging from about 30 to 60 % over about 50 to 60 % to about 60 to 75% of all women. The condition is most common among women between 30 and 50 years of age. In ICD-10 the condition is called diffuse cystic mastopathy, or, if there is epithelial proliferation, fibrosclerosis of breast. Other names for this condition include chronic cystic mastitis, fibrocystic mastopathy and mammary dysplasia. The condition has also been named after several people (see eponyms below). Since it is a very common disorder, some authors have argued that it should not be termed a "disease", whereas others feel that it meets the criteria for a disease. It is not a classic form of mastitis (breast inflammation). This entity has historically also been termed Bloodgood’s disease, Cooper's disease (after Sir Astley Paston Cooper, 1st baronet), Phocas' disease, Reclus’ disease and Reclus’ syndrome (after Paul Reclus), Reclus-Schimmelbusch disease, Schimmelbusch disease and Tillaux-Phocas disease. - Ferri, Fred F. (2018). Ferri's Clinical Advisor 2019: 5 Books in 1. Elsevier Health Sciences. p. 548. ISBN 9780323550765. - "Breast Masses (Breast Lumps)". Merck Manuals Professional Edition. Retrieved 3 November 2018. - Santen, RJ; Mansel, R (21 July 2005). "Benign breast disorders". The New England Journal of Medicine. 353 (3): 275–85. doi:10.1056/NEJMra035692. PMID 16034013. - "Fibrocystic Breast Condition".2010/04/13, MedicineNet.com - "Fibrocystic Breast Condition".2010/04/13 - Cann, Stephen A.; van Netten, Johannes P.; van Netten, Christiaan (2000). "Hypothesis: iodine, selenium and the development of breast cancer". Cancer Causes and Control (review). 11 (2): 121–127. doi:10.1023/A:1008925301459. ISSN 0957-5243. PMID 10710195. - Joseph E. Pizzorno; Michael T. Murray (14 September 2012). Textbook of Natural Medicine. Elsevier Health Sciences. p. 1371. ISBN 978-1-4377-2333-5. - Venturi, S. (2001). "Is there a role for iodine in breast diseases?". The Breast. 10 (5): 379–382. doi:10.1054/brst.2000.0267. PMID 14965610. - Aceves, C.; Anguiano, B.; Delgado, G. (2005). "Is iodine a gatekeeper of the integrity of the mammary gland?". Journal of Mammary Gland Biology and Neoplasia. 10 (2): 189–196. doi:10.1007/s10911-005-5401-5. PMID 16025225. - Vaidyanathan, L.; Barnard, K.; Elnicki, D M. (May 2002). "Benign Breast Disease: When To Treat, When To Reassure, When To Refer". Cleveland Clinic Journal of Medicine. 69 (5): 424–439. doi:10.3949/ccjm.69.5.425. - "Tests and diagnosis". Archived from the original on 2010-03-22.2010/04/13 - "Types of non-cancerous breast conditions".2010/04/13 - Gadducci A, Guerrieri ME, Genazzani AR (February 2012). "Benign breast diseases, contraception and hormone replacement therapy". Minerva Ginecologica. 64 (1): 67–74. PMID 22334232. - Ethel Sloane, Biology of Women, Cengage Learning, 2002, p. 200-201 - "Iodine: Fact Sheet for Health Professionals". NIH. Retrieved 2015-02-07. - Kessler JH (2004). "The effect of supraphysiologic levels of iodine on patients with cyclic mastalgia". The Breast Journal (Randomized Controlled Trial). 10 (4): 328–36. doi:10.1111/j.1075-122X.2004.21341.x. PMID 15239792. - Ethel Sloane, Biology of Women, Cengage Learning, 2002, p. 200 - Marshall, LM; Hunter, DJ; Connolly, JL; Schnitt, SJ; Byrne, C; London, SJ; Colditz, GA (1997). "Risk of breast cancer associated with atypical hyperplasia of lobular and ductal types". Cancer Epidemiology, Biomarkers & Prevention. 6 (5): 297–301. PMID 9149887. - Hartmann, L. C.; Sellers, T. A.; Frost, M. H.; Lingle, W. L.; Degnim, A. C.; Ghosh, K; Vierkant, R. A.; Maloney, S. D.; Pankratz, V. S.; Hillman, D. W.; Suman, V. J.; Johnson, J; Blake, C; Tlsty, T; Vachon, C. M.; Melton Lj, 3rd; Visscher, D. W. (2005). "Benign breast disease and the risk of breast cancer". New England Journal of Medicine. 353 (3): 229–37. doi:10.1056/NEJMoa044383. PMID 16034008. - Page, D. L.; Schuyler, P. A.; Dupont, W. D.; Jensen, R. A.; Plummer Jr, W. D.; Simpson, J. F. (2003). "Atypical lobular hyperplasia as a unilateral predictor of breast cancer risk: a retrospective cohort study". The Lancet. 361 (9352): 125–9. doi:10.1016/S0140-6736(03)12230-1. PMID 12531579. - Susan L. Norwoord (March 1990). "Fibrocystic Breast Disease An Update and Review". JOGNN – Journal of Obstetric Gynecologic, & Neonatal Nursing. 19 (2): 116–121. doi:10.1111/j.1552-6909.1990.tb01629.x. - Kelly A. McGarry; Iris L. Tong (6 July 2012). The 5-Minute Consult Clinical Companion to Women's Health. Lippincott Williams & Wilkins. p. 86. ISBN 978-1-4511-1654-0. - Roger P. Smith (1 December 2008). Netter's Obstetrics and Gynecology. Elsevier Health Sciences. p. 371. ISBN 978-1-4377-2137-9. - Disorders of breast (N60-N64) in ICD-10. - Atlantic Women’s Specialists. "Fibrocystic Breast Changes". Retrieved 21 June 2012. - Santen RJ, Mansel R (July 2005). "Benign breast disorders". N. Engl. J. Med. 353 (3): 275–85. doi:10.1056/NEJMra035692. PMID 16034013. - Gokhale, Sudheer (August 2009). "Ultrasound Characterization of Breast Masses". Indian Journal of Radiology and Imaging. 19 (3): 242–247. doi:10.4103/0971-3026.54878. PMC 2766883. PMID 19881096. - synd/1891 at Who Named It?	2	17	3	0	1	2	0.783689	6	3,888
Embryonic stem cell Embryonic stem cells (ES cells) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage preimplantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells. Isolating the embryoblast or inner cell mass (ICM) results in destruction of the blastocyst, which raises ethical issues, including whether or not embryos at the pre-implantation stage should be considered to have the same moral status as more developed human beings. Human ES cells measure approximately 14 while mouse ES cells are closer to 8 μm. - 1 Properties - 2 Utilities - 3 Adverse effect - 4 History - 5 Techniques and conditions for embryonic stem cell derivation and culture - 6 See also - 7 References - 8 External links Embryonic stem cells, derived from the blastocyst stage early mammalian embryos, are distinguished by their ability to differentiate into any cell type and by their ability to propagate. Embryonic stem cell's properties include having a normal karyotype, maintaining high telomerase activity, and exhibiting remarkable long-term proliferative potential. Embryonic stem cells of the inner cell mass are pluripotent, that is, they are able to differentiate to generate primitive ectoderm, which ultimately differentiates during gastrulation into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm. These include each of the more than 220 cell types in the adult body. Pluripotency distinguishes embryonic stem cells from adult stem cells found in adults; while embryonic stem cells can generate all cell types in the body, adult stem cells are multipotent and can produce only a limited number of cell types. If the pluripotent differentiation potential of embryonic stem cells could be harnessed in vitro, it might be a means of deriving cell or tissue types virtually to order. This would provide a radical new treatment approach to a wide variety of conditions where age, disease, or trauma has led to tissue damage or dysfunction. microRNA maintenance of pluripotency Additionally, under defined conditions, embryonic stem cells are capable of propagating themselves indefinitely in an undifferentiated state and have the capacity when provided with the appropriate signals to differentiate, presumably via the formation of precursor cells, to almost all mature cell phenotypes. This allows embryonic stem cells to be employed as useful tools for both research and regenerative medicine, because they can produce limitless numbers of themselves for continued research or clinical use. Because of their plasticity and potentially unlimited capacity for self-renewal, Embryonic stem cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease. Diseases that could potentially be treated by pluripotent stem cells include a number of blood and immune-system related genetic diseases, cancers, and disorders; juvenile diabetes; Parkinson's; blindness and spinal cord injuries. Besides the ethical concerns of stem cell therapy (see stem cell controversy), there is a technical problem of graft-versus-host disease associated with allogeneic stem cell transplantation. However, these problems associated with histocompatibility may be solved using autologous donor adult stem cells, therapeutic cloning, stem cell banks or more recently by reprogramming of somatic cells with defined factors (e.g. induced pluripotent stem cells). Embryonic stem cells provide hope that it will be possible to overcome the problems of donor tissue shortage and also, by making the cells immunocompatible with the recipient. Other potential uses of embryonic stem cells include investigation of early human development, study of genetic disease and as in vitro systems for toxicology testing. Potential clinical use According to a 2002 article in PNAS, "Human embryonic stem cells have the potential to differentiate into various cell types, and, thus, may be useful as a source of cells for transplantation or tissue engineering." Current research focuses on differentiating ES into a variety of cell types for eventual use as cell replacement therapies (CRTs). Some of the cell types that have or are currently being developed include cardiomyocytes (CM), neurons, hepatocytes, bone marrow cells, islet cells and endothelial cells. However, the derivation of such cell types from ESs is not without obstacles and hence current research is focused on overcoming these barriers. For example, studies are underway to differentiate ES in to tissue specific CMs and to eradicate their immature properties that distinguish them from adult CMs. Besides in the future becoming an important alternative to organ transplants, ES are also being used in field of toxicology and as cellular screens to uncover new chemical entities (NCEs) that can be developed as small molecule drugs. Studies have shown that cardiomyocytes derived from ES are validated in vitro models to test drug responses and predict toxicity profiles. ES derived cardiomyocytes have been shown to respond to pharmacological stimuli and hence can be used to assess cardiotoxicity like Torsades de Pointes. ES-derived hepatocytes are also useful models that could be used in the preclinical stages of drug discovery. However, the development of hepatocytes from ES has proven to be challenging and this hinders the ability to test drug metabolism. Therefore, current research is focusing on establishing fully functional ES-derived hepatocytes with stable phase I and II enzyme activity. Researchers have also differentiated ES into dopamine-producing cells with the hope that these neurons could be used in the treatment of Parkinson’s disease. ESs have also been differentiated to natural killer (NK) cells and bone tissue. Studies involving ES are also underway to provide an alternative treatment for diabetes. For example, D’Amour et al. were able to differentiate ES into insulin producing cells and researchers at Harvard University were able to produce large quantities of pancreatic beta cells from ES. Human embryonic stem cells as models of genetic disorders Several new studies have started to address this issue. This has been done either by genetically manipulating the cells, or more recently by deriving diseased cell lines identified by prenatal genetic diagnosis (PGD). This approach may very well prove invaluable at studying disorders such as Fragile-X syndrome, Cystic fibrosis, and other genetic maladies that have no reliable model system. Yury Verlinsky, a Russian-American medical researcher who specialized in embryo and cellular genetics (genetic cytology), developed prenatal diagnosis testing methods to determine genetic and chromosomal disorders a month and a half earlier than standard amniocentesis. The techniques are now used by many pregnant women and prospective parents, especially those couples with a history of genetic abnormalities or where the woman is over the age of 35, when the risk of genetically related disorders is higher. In addition, by allowing parents to select an embryo without genetic disorders, they have the potential of saving the lives of siblings that already had similar disorders and diseases using cells from the disease free offspring. Scientists have discovered a new technique for deriving human embryonic stem cell (ESC). Normal ESC lines from different sources of embryonic material including morula and whole blastocysts have been established. These findings allows researchers to construct ESC lines from embryos that acquire different genetic abnormalities; therefore, allowing for recognition of mechanisms in the molecular level that are possibly blocked that could impede the disease progression. The ESC lines originating from embryos with genetic and chromosomal abnormalities provide the data necessary to understand the pathways of genetic defects. A donor patient acquires one defective gene copy and one normal, and only one of these two copies is used for reproduction. By selecting egg cell derived from embryonic stem cells that have two normal copies, researchers can find variety of treatments for various diseases. To test this theory Dr. McLaughlin and several of his colleagues looked at whether parthenogenetic embryonic stem cells can be used in a mouse model that has thalassemia intermedia. This disease is described as an inherited blood disorder in which there is a lack of hemoglobin leading to anemia. The mouse model used, had one defective gene copy. Embryonic stem cells from an unfertilized egg of the diseased mice were gathered and those stem cells that contained only healthy hemoglobin genes were identified. The healthy embryonic stem cell lines were then converted into cells transplanted into the carrier mice. After five weeks, the test results from the transplant illustrated that these carrier mice now had a normal blood cell count and hemoglobin levels. Repair of DNA damage Differentiated somatic cells and ES cells use different strategies for dealing with DNA damage. For instance, human foreskin fibroblasts, one type of somatic cell, use non-homologous end joining (NHEJ), an error prone DNA repair process, as the primary pathway for repairing double-strand breaks (DSBs) during all cell cycle stages. Because of its error-prone nature, NHEJ tends to produce mutations in a cell’s clonal descendants. ES cells use a different strategy to deal with DSBs. Because ES cells give rise to all of the cell types of an organism including the cells of the germ line, mutations arising in ES cells due to faulty DNA repair are a more serious problem than in differentiated somatic cells. Consequently robust mechanisms are needed in ES cells to repair DNA damages accurately, and if repair fails, to remove those cells with un-repaired DNA damages. Thus, mouse ES cells predominantly use high fidelity homologous recombinational repair (HRR) to repair DSBs. This type of repair depends on the interaction of the two sister chromosomes formed during S phase and present together during the G2 phase of the cell cycle. HRR can accurately repair DSBs in one sister chromosome by using intact information from the other sister chromosome. Cells in the G1 phase of the cell cycle (i.e. after metaphase/cell division but prior the next round of replication) have only one copy of each chromosome (i.e. sister chromosomes aren’t present). Mouse ES cells lack a G1 checkpoint and do not undergo cell cycle arrest upon acquiring DNA damage. Rather they undergo programmed cell death (apoptosis) in response to DNA damage. Apoptosis can be used as a fail-safe strategy to remove cells with un-repaired DNA damages in order to avoid mutation and progression to cancer. Consistent with this strategy, mouse ES stem cells have a mutation frequency about 100-fold lower than that of isogenic mouse somatic cells. The major concern with the possible transplantation of ESC into patients as therapies is their ability to form tumors including teratoma. Safety issues prompted the FDA to place a hold on the first ESC clinical trial (see below), however no tumors were observed. The main strategy to enhance the safety of ESC for potential clinical use is to differentiate the ESC into specific cell types (e.g. neurons, muscle, liver cells) that have reduced or eliminated ability to cause tumors. Following differentiation, the cells are subjected to sorting by flow cytometry for further purification. ESC are predicted to be inherently safer than IPS cells because they are not genetically modified with genes such as c-Myc that are linked to cancer. Nonetheless, ESC express very high levels of the iPS inducing genes and these genes including Myc are essential for ESC self-renewal and pluripotency, and potential strategies to improve safety by eliminating Myc expression are unlikely to preserve the cells' "stemness". In 1964, researchers isolated a single type of cell from a teratocarcinoma, a tumor now known to be derived from a germ cell. These cells isolated from the teratocarcinoma replicated and grew in cell culture as a stem cell and are now known as embryonal carcinoma (EC) cells. Although similarities in morphology and differentiating potential (pluripotency) led to the use of EC cells as the in vitro model for early mouse development, EC cells harbor genetic mutations and often abnormal karyotypes that accumulated during the development of the teratocarcinoma. These genetic aberrations further emphasized the need to be able to culture pluripotent cells directly from the inner cell mass. In 1981, embryonic stem cells (ES cells) were independently first derived from mouse embryos by two groups. Martin Evans and Matthew Kaufman from the Department of Genetics, University of Cambridge published first in July, revealing a new technique for culturing the mouse embryos in the uterus to allow for an increase in cell number, allowing for the derivation of ES cells from these embryos. Gail R. Martin, from the Department of Anatomy, University of California, San Francisco, published her paper in December and coined the term “Embryonic Stem Cell”. She showed that embryos could be cultured in vitro and that ES cells could be derived from these embryos. In 1998, a breakthrough occurred when researchers, led by James Thomson at the University of Wisconsin-Madison, first developed a technique to isolate and grow human embryonic stem cells in cell culture. First clinical trial On January 23, 2009, Phase I clinical trials for transplantation of oligodendrocytes (a cell type of the brain and spinal cord) derived from human ES cells into spinal cord-injured individuals received approval from the U.S. Food and Drug Administration (FDA), marking it the world's first human ES cell human trial. The study leading to this scientific advancement was conducted by Hans Keirstead and colleagues at the University of California, Irvine and supported by Geron Corporation of Menlo Park, CA, founded by Michael D. West, PhD. A previous experiment had shown an improvement in locomotor recovery in spinal cord-injured rats after a 7-day delayed transplantation of human ES cells that had been pushed into an oligodendrocytic lineage. The phase I clinical study was designed to enroll about eight to ten paraplegics who have had their injuries no longer than two weeks before the trial begins, since the cells must be injected before scar tissue is able to form. The researchers emphasized that the injections were not expected to fully cure the patients and restore all mobility. Based on the results of the rodent trials, researchers speculated that restoration of myelin sheathes and an increase in mobility might occur. This first trial was primarily designed to test the safety of these procedures and if everything went well, it was hoped that it would lead to future studies that involve people with more severe disabilities. The trial was put on hold in August 2009 due to FDA concerns regarding a small number of microscopic cysts found in several treated rat models but the hold was lifted on July 30, 2010. In October 2010 researchers enrolled and administered ESTs to the first patient at Shepherd Center in Atlanta. The makers of the stem cell therapy, Geron Corporation, estimated that it would take several months for the stem cells to replicate and for the GRNOPC1 therapy to be evaluated for success or failure. In November 2011 Geron announced it was halting the trial and dropping out of stem cell research for financial reasons, but would continue to monitor existing patients, and was attempting to find a partner that could continue their research. In 2013 BioTime (NYSE MKT: BTX), led by CEO Dr. Michael D. West, acquired all of Geron's stem cell assets, with the stated intention of restarting Geron's embryonic stem cell-based clinical trial for spinal cord injury. Techniques and conditions for embryonic stem cell derivation and culture Derivation of human embryonic stem cells In vitro fertilization generates multiple embryos. The surplus of embryos is not clinically used or is unsuitable for implantation into the patient, and therefore may be donated by the donor with consent. Human embryonic stem cells can be derived from these donated embryos or additionally they can also be extracted from cloned embryos using a cell from a patient and a donated egg. The inner cell mass (cells of interest), from the blastocyst stage of the embryo, is separated from the trophectoderm, the cells that would differentiate into extra-embryonic tissue. Immunosurgery, the process in which antibodies are bound to the trophectoderm and removed by another solution, and mechanical dissection are performed to achieve separation. The resulting inner cell mass cells are plated onto cells that will supply support. The inner cell mass cells attach and expand further to form a human embryonic cell line, which are undifferentiated. These cells are fed daily and are enzymatically or mechanically separated every four to seven days. For differentiation to occur, the human embryonic stem cell line is removed from the supporting cells to form embryoid bodies, is co-cultured with a serum containing necessary signals, or is grafted in a three-dimensional scaffold to result. Derivation of embryonic stem cells from other animals Embryonic stem cells are derived from the inner cell mass of the early embryo, which are harvested from the donor mother animal. Martin Evans and Matthew Kaufman reported a technique that delays embryo implantation, allowing the inner cell mass to increase. This process includes removing the donor mother’s ovaries and dosing her with progesterone, changing the hormone environment, which causes the embryos to remain free in the uterus. After 4–6 days of this intrauterine culture, the embryos are harvested and grown in in vitro culture until the inner cell mass forms “egg cylinder-like structures,” which are dissociated into single cells, and plated on fibroblasts treated with mitomycin-c (to prevent fibroblast mitosis). Clonal cell lines are created by growing up a single cell. Evans and Kaufman showed that the cells grown out from these cultures could form teratomas and embryoid bodies, and differentiate in vitro, all of which indicating that the cells are pluripotent. Gail Martin derived and cultured her ES cells differently. She removed the embryos from the donor mother at approximately 76 hours after copulation and cultured them overnight in a medium containing serum. The following day, she removed the inner cell mass from the late blastocyst using microsurgery. The extracted inner cell mass was cultured on fibroblasts treated with mitomycin-c in a medium containing serum and conditioned by ES cells. After approximately one week, colonies of cells grew out. These cells grew in culture and demonstrated pluripotent characteristics, as demonstrated by the ability to form teratomas, differentiate in vitro, and form embryoid bodies. Martin referred to these cells as ES cells. It is now known that the feeder cells provide leukemia inhibitory factor (LIF) and serum provides bone morphogenetic proteins (BMPs) that are necessary to prevent ES cells from differentiating. These factors are extremely important for the efficiency of deriving ES cells. Furthermore, it has been demonstrated that different mouse strains have different efficiencies for isolating ES cells. Current uses for mouse ES cells include the generation of transgenic mice, including knockout mice. For human treatment, there is a need for patient specific pluripotent cells. Generation of human ES cells is more difficult and faces ethical issues. So, in addition to human ES cell research, many groups are focused on the generation of induced pluripotent stem cells (iPS cells). Potential method for new cell line derivation On August 23, 2006, the online edition of Nature scientific journal published a letter by Dr. Robert Lanza (medical director of Advanced Cell Technology in Worcester, MA) stating that his team had found a way to extract embryonic stem cells without destroying the actual embryo. This technical achievement would potentially enable scientists to work with new lines of embryonic stem cells derived using public funding in the USA, where federal funding was at the time limited to research using embryonic stem cell lines derived prior to August 2001. In March, 2009, the limitation was lifted. Recently, it was shown that pluripotent stem cells highly similar to embryonic stem cells can be generated by the delivery of three genes (Oct4, Sox2, and Klf4) to differentiated cells. The delivery of these genes "reprograms" differentiated cells into pluripotent stem cells, allowing for the generation of pluripotent stem cells without the embryo. Because ethical concerns regarding embryonic stem cells typically are about their derivation from terminated embryos, it is believed that reprogramming to these "induced pluripotent stem cells" (iPS cells) may be less controversial. Both human and mouse cells can be reprogrammed by this methodology, generating both human pluripotent stem cells and mouse pluripotent stem cells without an embryo. This may enable the generation of patient specific ES cell lines that could potentially be used for cell replacement therapies. In addition, this will allow the generation of ES cell lines from patients with a variety of genetic diseases and will provide invaluable models to study those diseases. However, as a first indication that the induced pluripotent stem cell (iPS) cell technology can in rapid succession lead to new cures, it was used by a research team headed by Rudolf Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, to cure mice of sickle cell anemia, as reported by Science journal's online edition on December 6, 2007. On January 16, 2008, a California based company, Stemagen, announced that they had created the first mature cloned human embryos from single skin cells taken from adults. These embryos can be harvested for patient matching embryonic stem cells. Contamination by reagents used in cell culture The online edition of Nature Medicine published a study on January 24, 2005, which stated that the human embryonic stem cells available for federally funded research are contaminated with non-human molecules from the culture medium used to grow the cells. It is a common technique to use mouse cells and other animal cells to maintain the pluripotency of actively dividing stem cells. The problem was discovered when non-human sialic acid in the growth medium was found to compromise the potential uses of the embryonic stem cells in humans, according to scientists at the University of California, San Diego. However, a study published in the online edition of Lancet Medical Journal on March 8, 2005 detailed information about a new stem cell line that was derived from human embryos under completely cell- and serum-free conditions. After more than 6 months of undifferentiated proliferation, these cells demonstrated the potential to form derivatives of all three embryonic germ layers both in vitro and in teratomas. 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PMID 15885296. \|Wikimedia Commons has media related to Embryonic stem cells.\| - Understanding Stem Cells: A View of the Science and Issues from the National Academies - National Institutes of Health - University of Oxford practical workshop on pluripotent stem cell technology - Fact sheet on embryonic stem cells - Fact sheet on ethical issues in embryonic stem cell research - Information & Alternatives to Embryonic Stem Cell Research - A blog focusing specifically on ES cells and iPS cells including research, biotech, and patient-oriented issues	2	45	10	0	5	2	0.310321	17	8,400
... valve. Also, a narrowing of the aortic valve (aortic stenosis) can be associated with leaking. High blood pressure (hypertension). High blood pressure may stretch the root of the aorta where the aortic valve sits. The valve flaps ( ... ... pulmonary valve and aortic valve. Each valve has flaps (cusps or leaflets) that open and close once ... valve consists of three tightly fitting, triangular-shaped flaps of tissue called cusps. Some children are born ... Oliemy, Ahmed; Al-Attar, Nawwar Transcatheter aortic valve implantation was developed to offer a therapeutic solution to patients with severe symptomatic aortic stenosis who are not candidates for conventional aortic valve replacement. The improvement in transcatheter aortic valve implantation outcomes is still of concern in the areas of stroke, vascular injury, heart block, paravalvular regurgitation and valve durability. Concomitantly, the progress, both technical and in terms of material advances of transcatheter valve systems, as well as in patient selection, renders transcatheter aortic valve implantation an increasingly viable treatment for more and more patients with structural heart disease. ... fully will restrict blood flow. This is called aortic stenosis. If there is also a leak, it is ... TAVR is used for people with severe aortic stenosis who aren't ... valve . In adults, aortic stenosis usually occurs due to calcium ... Schnell E, Wollenek G, Maurer G, Baumgartner H, Lang IM. Mechanisms underlying aortic dilatation in congenital aortic valve malformation . Circulation...1999; 99(16):2138-2143. 10. Roberts CS, Roberts WC. Dissection of the aorta associated with congenital malformation of the aortic valve. J Am Coll... congenital heart defect, often diagnosed incidentally or as a consequence of an associated condition. Patients with this anomaly are at increased risk ... of the heart is reduced. This is called aortic stenosis. The aortic valve can be replaced using: Minimally ... RN, Wang A. Percutaneous heart valve replacement for aortic stenosis: state of the evidence. Ann Intern Med . 2010; ... The increasing incidence of aortic stenosis and greater co-morbidities and risk profiles of the contemporary patient population has driven the development of minimally invasive aortic valve surgery and percutaneous transcatheter aortic valve implantation (TAVI) techniques to reduce surgical trauma. Recent technological developments have led to an alternative minimally invasive option which avoids the placement and tying of sutures, known as “sutureless” or rapid deployment aortic valves. Potential advantages for sutureless aortic prostheses include reducing cross-clamp and cardiopulmonary bypass (CPB) duration, facilitating minimally invasive surgery and complex cardiac interventions, whilst maintaining satisfactory hemodynamic outcomes and low paravalvular leak rates. However, given its recent developments, the majority of evidence regarding sutureless aortic valve replacement (SU-AVR) is limited to observational studies and there is a paucity of adequately-powered randomized studies. Recently, the International Valvular Surgery Study Group (IVSSG) has formulated to conduct the Sutureless Projects, set to be the largest international collaborative group to investigate this technology. This keynote lecture will overview the use, the potential advantages, the caveats, and current evidence of sutureless and rapid deployment aortic valve replacement (AVR). PMID:25870807 Devlin, A B; Goldstraw, P; Caves, P K Rheumatoid aortic valve disease is uncommon. and there are few reports of valve replacement in this condition. Aortic valve replacement and partial pericardiectomy was performed in a patient with acute rheumatoid aortitis and aortic incompetence. Previous reports suggest that any patient with rheumatoid arthritis who develops cardiac symptoms should be carefully assessed for surgically treatable involvement of the pericardium or heart valves. Images PMID:725829 Aortic Valve Insufficiency; Aortic Valve Regurgitation; Aortic Valve Stenosis; Aortic Valve Incompetence; Mitral Valve Insufficiency; Mitral Valve Regurgitation; Mitral Valve Stenosis; Mitral Valve Incompetence Aortic prosthetic valve endocarditis (PVE) is a potentially life-threatening disease. Mortality and incidence of infective endocarditis have been reduced in the past 30 years. Medical treatment of aortic PVE may be successful in patients who have a prompt response after antibiotic treatment and who do not have prosthetic dysfunction. In advanced stages, antibiotic therapy alone is insufficient to control the disease, and surgical intervention is necessary. Surgical treatment may be lifesaving, but it is still associated with considerable morbidity and mortality. The aim of surgery is to perform a radical excision of all infected and necrotic tissue, reconstruction of the left ventricle outflow tract, and replacement of the aortic valve. There is no unanimous consensus on which is the optimal prosthesis to implant in this context, and several surgical techniques have been suggested. We aim to analyze the efficacy of the surgical treatment and discuss the issue of valve selection in patients with aortic valve endocarditis. PMID:27785132 Castrovinci, Sebastiano; Emmanuel, Sam; Moscarelli, Marco; Murana, Giacomo; Caccamo, Giuseppa; Bertolino, Emanuela Clara; Nasso, Giuseppe; Speziale, Giuseppe; Fattouch, Khalil Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replacement is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper sternotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease. PMID:27582764 Cemri, M; Cengel, A; Timurkaynak, T Congenital aortic valve anomalies are quite a rare finding in echocardiographic examinations. A case of a 19 year old man with a pentacuspid aortic valve without aortic stenosis and regurgitation, detected by transoesophageal echocardiography, is presented. Keywords: pentacuspid aortic valve; echocardiography PMID:10995427 Schramm, René; Kupatt, Christian; Becker, Christoph; Bombien, René; Reichart, Bruno; Sodian, Ralf; Schmitz, Christoph A 77-year-old male patient was scheduled for transcatheter aortic valve implantation for symptomatic and severe aortic valve stenosis. Severe multidirectional kinking of the aorta based on aortic coarctation did not allow for the transfemoral, but only for the transapical approach. The procedure was complicated because of the technically challenging retrograde passage of the transfemorally inserted pig-tail catheter required for intraoperative angiography of the aortic root. Correct positioning of the pig-tail catheter into the ascending aorta was accomplished by use of a loop snare, which was advanced into the descending aorta via the antegrade route, passing the cardiac apex, the stenotic aortic valve, and the coarctation-associated kinking. The pig-tail catheter tip was manipulated into the loop snare, pulled traverse the coarctation, and released within the proximal ascending aorta. Subsequent procedures were uneventful and followed the standardized protocol. A 29 mm Edwards Lifescience transcatheter Sapien bioprosthesis was successfully implanted. Georg Thieme Verlag KG Stuttgart · New York. Jahren, Silje Ekroll; Winkler, Bernhard Michael; Heinisch, Paul Philipp; Wirz, Jessica; Carrel, Thierry; Obrist, Dominik In this study, the influence of aortic root distensibility on the haemodynamic parameters and valve kinematics of a bioprosthetic aortic valve was investigated in a controlled in vitro experiment. An Edwards INTUITY Elite 21 mm sutureless aortic valve (Edwards Lifesciences, Irvine, CA, USA) was inserted in three transparent aortic root phantoms with different wall thicknesses (0.55, 0.85 and 1.50 mm) mimicking different physiological distensibilities. Haemodynamic measurements were performed in an in vitro flow loop at heart rates of 60, 80 and 100 bpm with corresponding cardiac outputs of 3.5, 4.0 and 5.0 l/min and aortic pressures of 100/60, 120/90 and 145/110 mmHg, respectively. Aortic valve kinematics were assessed using a high-speed camera. The geometric orifice area (GOA) was measured by counting pixels in the lumen of the open aortic valve. The effective orifice area (EOA) was calculated from the root-mean-square value of the systolic aortic valve flow rate and the mean systolic trans-valvular pressure gradient. The tested aortic root phantoms reproduce physiological distensibilities of healthy individuals in age groups ranging from 40 to 70 years (±10 years). The haemodynamic results show only minor differences between the aortic root phantoms: the trans-valvular pressure gradient tends to increase for stiffer aortic roots, whereas the systolic aortic valve flow rate remains constant. As a consequence, the EOA decreased slightly for less distensible aortic roots. The GOA and the aortic valve opening and closing velocities increase significantly with reduced distensibility for all haemodynamic measurements. The resulting mean systolic flow velocity in the aortic valve orifice is lower for the stiffer aortic root. Aortic root distensibility may influence GOA and aortic valve kinematics, which affects the mechanical load on the aortic valve cusps. Whether these changes have a significant effect on the onset of structural valve deterioration of bioprosthetic Transcatheter aortic valve implantation and transcatheter mitral valve repair (MitraClip) procedures have been performed worldwide. In this paper, we review the use of two-dimensional and three-dimensional transesophageal echo for guiding transcatheter aortic valve replacement and mitral valve repair. PMID:23019387 ... body Watch the video below as Dr. Robbin Cohen describes aortic stenosis Video of Robbin G. Cohen, MD on Aortic Stenosis Causes and Symptoms Causes ... when having dental work. Reviewed by: Robbin G. Cohen, MD, with assistance from John Hallsten and Travis ... Lamarche, Yoan; Cartier, Raymond; Denault, André Y; Basmadjian, Arsène; Berry, Colin; Laborde, Jean-Claude; Bonan, Raoul Surgical aortic valve replacement is the only recommended treatment for significant aortic valve stenosis. Percutaneous aortic valve replacement appears to be a novel option for high-risk patients. We report the implantation of the ReValving system (CoreValve, Paris, France) in a 64-year-old woman who was refused aortic valve replacement surgery for critical aortic stenosis and left ventricular dysfunction because of severe pulmonary fibrosis. After anesthesia, the patient was put on femorofemoral cardiopulmonary bypass, and underwent a balloon valvuloplasty with subsequent retrograde aortic valve replacement by the ReValving system. Transesophageal echocardiographic monitoring of the patient's hemodynamics showed immediate improvements of the valvular area and left ventricular ejection fraction and only traces of paravalvular leaks. The patient was easily weaned from ventilation and resumed activity soon after the surgery. A multidisciplinary approach is presently necessary to offer a reliable and safe procedure. Minimally invasive aortic valve replacement (MIAVR) is defined as aortic valve replacement avoiding full sternotomy. Common approaches include a partial sternotomy right thoracotomy, and a parasternal approach. MIAVR has been shown to have advantages over conventional AVR such as shorter length of stay and smaller amount of blood transfusion and better cosmesis. However, it is also known to have disadvantages such as longer cardiopulmonary bypass and aortic cross-clamp times and potential complications related to peripheral cannulation. Appropriate patient selection is very important. Since the procedure is more complex than conventional AVR, more intensive teamwork in the operating room is essential. Additionally, a team approach during postoperative management is critical to maximize the benefits of MIAVR. ... evaluation of aortic stenosis in adults. http://www.uptodate.com/home. Accessed April 29, 2014. Mohty D, ... Valvular heart disease in elderly adults. http://www.uptodate.com/home. Accessed May 2, 2014. Bonow RO, ... Renewed interest for aortic valve disease has evolved in recent years. Aortic valve replacement has become the second most frequent cause of cardiac surgery, following coronary bypass surgery. In addition, the etiologic and physiopathologic knowledge of this disorder has improved. In the present paper we analyze three aspects of the disease which are, at present, the subject of study and controversy: first, we discuss the possible relationship between degenerative aortic stenosis and atherosclerosis; second, the involvement of the aortic root in cases of bicuspid aortic valve; and third, the surgical indications in asymptomatic patients with either aortic stenosis or regurgitation. Dohmen, Pascal M.; Lehmkuhl, Lukas; Borger, Michael A.; Misfeld, Martin; Mohr, Friedrich W. Patient: Female, 61 Final Diagnosis: Tissue degeneration Symptoms: Dyspnea Medication: — Clinical Procedure: Redo valve replacement Specialty: Surgery Objective: Rare disease Background: We present a unique case of a 61-year-old female patient with homograft deterioration after redo surgery for prosthetic valve endocarditis with root abscess. Case Report: The first operation was performed for type A dissection with root, arch, and elephant trunk replacement of the thoracic aorta. The present re-redo surgery was performed as valve-in-valve with a sutureless aortic biopros-thesis. The postoperative course was uneventful and the patient was discharged on day 6. Conclusions: The current case report demonstrates that sutureless bioprostheses are an attractive option for surgical valve-in-valve procedures, which can reduce morbidity and mortality. PMID:27694795 Paton, B C; Pine, M B De Bakey prostheses were inserted in 29 patients with aortic valve disease between October, 1970, and May, 1972. Ten patients have died, but all but one of the remaining 19 have beel followed for a minimum of 19 months. Evaluation of the results in these subjects indicates that the function of the De Bakey valve compares favorably with that of other aortic valve prostheses. Pasic, Miralem; Dreysse, Stephan; Drews, Thorsten; Buz, Semih; Unbehaun, Axel; Kukucka, Marian; Mladenow, Alexandar; Hetzer, Roland Transapical aortic valve implantation carries some degree of uncertainty regarding the definitive valve position. We added angiographic visualization of the aortic root while the prosthetic valve is being slowly deployed. It enables easy correction of the position of the valve so that perfect alignment can be achieved of the relationships between the prosthetic valve, aortic valve annulus, aortic cusps, and the coronary arteries. Baikoussis, Nikolaos G.; Dedeilias, Panagiotis; Argiriou, Michalis Aortic valve replacement (AVR) in patients with a small aortic annulus is a challenging issue. The importance of prosthesis–patient mismatch (PPM) post aortic valve replacement (AVR) is controversial but has to be avoided. Many studies support the fact that PPM has a negative impact on short and long term survival. In order to avoid PPM, aortic root enlargement may be performed. Alternatively and keeping in mind that often some comorbidities are present in old patients with small aortic root, the Perceval S suturelles valve implantation could be a perfect solution. The Perceval sutureless bioprosthesis provides reasonable hemodynamic performance avoiding the PPM and providing the maximum of aortic orifice area. We would like to see in the near future the role of the aortic root enlargement techniques in the era of surgical implantation of the sutureless valve (SAVR) and the transcatheter valve implantation (TAVI). PMID:28028424 Yamanaka, Katsuhiro; Okada, Kenji; Okita, Yutaka A 67-year old man with ascending aortic aneurysm was referred because of a quadricuspid aortic valve. He underwent aortic root replacement with a valve-sparing technique. Under deep hypothermic circulatory arrest, replacement of the ascending aorta was successfully performed. The postoperative course was uneventful without recurrence of aortic regurgitation. Yates, A. K. The promising qualities of autologous fascia lata in heart valve replacement have resulted in a search for improved methods of fascial heart valve manufacture. This paper describes a simply made and inserted and reliably competent unsupported fascial valve for aortic valve replacement. Images PMID:5576536 Gunning, A. J.; Meade, J. B. Heterologous aortic valves are used in many clinics as replacements for diseased human aortic and mitral valves. These valves possess all the advantages of homologous aortic valves and are more easily available to the surgeon. The heterologous valve also provides a greater choice of valve size than does the homograft; this can be of importance when replacing the mitral valve. Heterograft valves, like homografts, are usually preserved for periods ranging from a few days to a few months before insertion into a patient. Four methods of preservation, described, are currently in use. This study compares the effects of these four methods of preservation when pig valves are transplanted into the dog's aorta. Images PMID:5576535 Olivieri, Laura J; Baba, Ridhwan Y; Arai, Andrew E; Bandettini, W Patricia; Rosing, Douglas R; Bakalov, Vladimir; Sachdev, Vandana; Bondy, Carolyn A Congenital aortic valve fusion is associated with aortic dilation, aneurysm, and rupture in girls and women with Turner syndrome. Our objective was to characterize aortic valve structure in subjects with Turner syndrome and to determine the prevalence of aortic dilation and valve dysfunction associated with different types of aortic valves. The aortic valve and thoracic aorta were characterized by cardiovascular MRI in 208 subjects with Turner syndrome in an institutional review board-approved natural history study. Echocardiography was used to measure peak velocities across the aortic valve and the degree of aortic regurgitation. Four distinct valve morphologies were identified: tricuspid aortic valve, 64% (n=133); partially fused aortic valve, 12% (n=25); bicuspid aortic valve, 23% (n=47); and unicuspid aortic valve, 1% (n=3). Age and body surface area were similar in the 4 valve morphology groups. There was a significant trend, independent of age, toward larger body surface area-indexed ascending aortic diameters with increasing valve fusion. Ascending aortic diameters were (mean±SD) 16.9±3.3, 18.3±3.3, and 19.8±3.9 mm/m(2) (P<0.0001) for tricuspid aortic valve, partially fused aortic valve, and bicuspid aortic valve+unicuspid aortic valve, respectively. Partially fused aortic valve, bicuspid aortic valve, and unicuspid aortic valve were significantly associated with mild aortic regurgitation and elevated peak velocities across the aortic valve. Aortic valve abnormalities in Turner syndrome occur with a spectrum of severity and are associated with aortic root dilation across age groups. Partial fusion of the aortic valve, traditionally regarded as an acquired valve problem, had an equal age distribution and was associated with an increased ascending aortic diameters. Durand, Eric; Tron, Christophe; Eltchaninoff, Hélène We report the case of a 78-year-old woman admitted for cardiogenic shock related to acute and early failure (severe aortic regurgitation) of a Perceval sutureless aortic bioprosthesis (Sorin Group, Saluggia, Italy). Clinical stability was achieved using rescue transfemoral transcatheter aortic valve-in-valve implantation with an Edwards SAPIEN 3 prosthesis (Edwards Lifesciences, Irvine, CA). To our knowledge, we report herein the first case of successful valve-in-valve implantation using a SAPIEN 3 transcatheter heart valve in a sutureless bioprosthetic aortic valve with acute and early deterioration. Luo, Wenzong; Wang, Xinxin; Li, Jing; Mu, Yun; Ni, Yiming Abstract Background: Intermittent stuck valve after mechanical valve replacement surgery is a very rare and severe complication. Case summary: We present 1 case of a 53-year-old woman after aortic valve replacement for severe aortic valve stenosis combined with hypertrophy septum. She was diagnosed with intermittent stuck valve only 1 day after surgery by clinical symptoms, intraoperative transoesophageal echocardiogram, and intraoperative findings. Conclusions: Although indications for concomitant myectomy during aortic valve replacement are not clear, we recommend myectomy to prevent stuck valve after St Jude Medical Regent prosthesis replacement for severe aortic valve stenosis combined with hypertrophy septum. PMID:28248877 Iwata, Shinichi; Walker, Marcella Donovan; Di Tullio, Marco R.; Hyodo, Eiichi; Jin, Zhezhen; Liu, Rui; Sacco, Ralph L.; Homma, Shunichi Context: It is unclear whether cardiovascular disease is present in primary hyperparathyroidism (PHPT). Objective: Aortic valve structure and function were compared in PHPT patients and population-based controls. Design: This is a case-control study. Setting: The study was conducted in a university hospital metabolic bone disease unit. Participants: We studied 51 patients with PHPT and 49 controls. Outcome Measures: We measured the aortic valve calcification area and the transaortic pressure gradient. Results: Aortic valve calcification area was significantly higher in PHPT (0.24 ± 0.02 vs. 0.17 ± 0.02 cm2, p<0.01), although there was no difference in the peak transaortic pressure gradient, a functional measure of valvular calcification (5.6 ± 0.3 vs. 6.0 ± 0.3 mm Hg, P = 0.39). Aortic valve calcification area was positively associated with PTH (r = 0.34; P < 0.05) but not with serum calcium, phosphorus, or 25-hydroxyvitamin D levels or with calcium-phosphate product. Serum PTH level remained an independent predictor of aortic valve calcification area after adjustment for age, sex, body mass index, smoking status, history of hypercholesterolemia and hypertension, and estimated glomerular filtration rate. Conclusions: Mild PHPT is associated with subclinical aortic valve calcification. PTH, but not serum calcium concentration, predicted aortic valve calcification. PTH was a more important predictor of aortic valve calcification than well-accepted cardiovascular risk factors. PMID:22031523 Kim, Dae-Hee; Handschumacher, Mark D.; Levine, Robert A.; Sun, Byung Joo; Jang, Jeong Yoon; Yang, Dong Hyun; Kang, Joon-Won; Song, Jong-Min; Kang, Duk-Hyun; Lim, Tae-Hwan; Song, Jae-Kwan Background The 3-dimensional relationship between aortic root and cusp is essential to understand the mechanism of aortic regurgitation (AR) because of aortic root dilatation (ARD). We sought to test the hypothesis that the stretched cusps in ARD enlarge to compensate for ARD. Methods and Results Computed tomography imaged 92 patients (57 with ARD, 29 with moderate to severe AR, 28 without significant AR) and 35 normal controls. Specialized 3-dimensional software measured individual cusp surface areas relative to maximal mid-sinus cross-sectional area and minimal 3-dimensional annular area, coaptation area fraction, and asymmetry of sinus volumes and intercommissural distances. Total open cusp surface area increased (P<0.001) from 7.6±1.4 cm2/m2 in normals to 12.9±2.2 cm2/m2 in AR-negative and 15.2±3.3 cm2/m2 in AR-positive patients. However, the ratio of closed cusp surface area to maximal mid-sinus area, reflecting cusp adaptation, decreased from normals to AR-negative to AR-positive patients (1.38±0.20, 1.15±0.15, 0.88±0.15; P<0.001), creating the lowest coaptation area fraction. Cusp distensibility (closed diastolic versus open area) decreased from 20% in controls and AR-negative patients to 5% in AR-positive patients (P<0.001). Multivariate determinants of AR and coaptation area fraction reflected both sinus size and cusp-to-annular adaptation. ARD was also progressively asymmetrical with root size, and individual cusp surface areas failed to match this asymmetry. Conclusions Aortic cusp enlargement occurs in ARD, but cusp adaptation and distensibility become limited in prominent, asymmetrical ARD, leading to AR. Optimal AR repair tailored to individual patient anatomy can benefit from appreciating valve adaptation and 3-dimensional relationships; understanding cusp adaptation mechanisms may ultimately provide therapeutic opportunities to improve such compensation. PMID:25051951 Leopold, Jane A. Acquired aortic valve disease and valvular calcification is highly prevalent in adult populations worldwide and is associated with significant cardiovascular morbidity and mortality. At present, there are no medical therapies that will prevent or regress aortic valve calcification or stenosis and surgical or transcatheter aortic valve replacement remain the only effective therapies for treating this disease. In the setting of valve injury as a result of exposure to biochemical mediators or hemodynamic forces, normal homeostatic processes are disrupted resulting in extracellular matrix degradation, aberrant matrix deposition and fibrosis, inflammatory cell infiltration, lipid accumulation, and neoangiogenesis of the valve tissue and, ultimately, calcification of the valve. Calcification of the aortic valve is now understood to be an active process that involves the coordinated actions of resident valve endothelial and interstitial cells, circulating inflammatory and immune cells, and bone marrow-derived cells. These cells may undergo a phenotype transition to become osteoblast-like cells and elaborate bone matrix, endothelial-to-mesenchymal transition, and form matrix vesicles that serve as a nidus for microcalcifications. Each of these mechanisms has been shown to contribute to aortic valve calcification suggesting that strategies that target these cellular events may lead to novel therapeutic interventions to halt the progression or reverse aortic valve calcification. PMID:22896576 Koizumi, Shigeki; Ehara, Natsuhiko; Nishiya, Kenta; Koyama, Tadaaki Late transcatheter heart valve embolization is a rare but life-threatening complication of transcatheter aortic valve implantation. Surgical intervention is performed for most cases, but some cases were treated by valve-in-valve transcatheter aortic valve implantation. We describe a patient in whom a 29-mm Edwards SAPIEN XT valve migrated into the left ventricular outflow tract 41 days after the initial implantation. We tried to perform valve-in-valve transcatheter aortic valve implantation using a transfemoral approach. As soon as the second transcatheter heart valve touched the first implanted valve, it fell into the left ventricle. Immediate surgical intervention was required. The first valve was removed, and surgical aortic valve replacement was successfully performed. In conclusion, we should choose surgical aortic valve replacement for late transcatheter heart valve embolization. Even if we need to treat by catheter intervention, transapical approach may be better. Pizzighini, S; Finet, G; Obadia, J-F; Revel, D; Bresson, D; Rioufol, G Transcatheter aortic valve implantation is a therapeutic option for high-risk patients with severe aortic valve stenosis and with cardiac symptoms. This procedure requires the preliminary evaluation by a "heart team" and presents some contraindications. We report the case of a 58-year-old man with severe bicuspid aortic valve stenosis and cardiogenic shock. In spite of contraindications and because of the failure of balloon aortic valvuloplasty, transcatheter aortic valve implantation was performed in emergency. Copyright © 2014 Elsevier Masson SAS. All rights reserved. Antunes, M J The favorable results of mitral valvuloplasty when compared with valve replacement have renewed the interest of many surgeons in aortic valve repair. However, these efforts have, for the most part, been unsuccessful. Also, the results of aortic valve replacement are usually better than those of mitral valve replacement. Yet, some patients appear to derive benefit from a conservative aortic valve procedure. The best examples are mild or moderate aortic valve disease associated with mitral valve or coronary artery disease, which constitute the primary indication for operation, where "prophylactic" aortic valve replacement does not appear justifiable. Other possible indications for aortic valvuloplasty includes patient's lack of compliance or contraindication to anticoagulation in young patients. Senile aortic stenosis, in very old patients with a small annulus, preserved leaflet morphology and nonsignificant commissural fusion should be considered for repair. However, since the procedure is not easily reproducible and the results not uniformly predictable, it cannot be recommended for generalized use. Nonetheless, experienced surgeons should be encouraged to continue these efforts. Sousa, Maria João; Alves, Vasco; Cabral, Sofia; Antunes, Nuno; Pereira, Luís Sousa; Oliveira, Filomena; Silveira, João; Torres, Severo Mitral valve aneurysms are rare and occur most commonly in association with aortic valve endocarditis. Transesophageal echocardiography is the most sensitive imaging modality for the diagnosis of this entity and its potential complications, such as leaflet rupture and mitral regurgitation, which mandate prompt surgical intervention. We present the case of a 70-year-old male patient with aortic valve endocarditis complicated with a ruptured aneurysm of the anterior mitral valve leaflet and associated severe mitral regurgitation, diagnosed by transesophageal echocardiography, with impressive images. We hypothesized that the aneurysm developed through direct extension of infection from the aortic valve or from a prolapsing aortic vegetation, with abscess formation and subsequent rupture and drainage. This case highlights the importance of appropriate imaging for early detection and timely surgical intervention (repair or replacement) to prevent fatal outcomes. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved. Córdoba-Soriano, Juan G; Puri, Rishi; Amat-Santos, Ignacio; Ribeiro, Henrique B; Abdul-Jawad Altisent, Omar; del Trigo, María; Paradis, Jean-Michel; Dumont, Eric; Urena, Marina; Rodés-Cabau, Josep Despite the rapid global uptake of transcatheter aortic valve implantation, valve trombosis has yet to be systematically evaluated in this field. The aim of this study was to determine the clinical characteristics, diagnostic criteria, and treatment outcomes of patients diagnosed with valve thrombosis following transcatheter aortic valve implantation through a systematic review of published data. Literature published between 2002 and 2012 on valve thrombosis as a complication of transcatheter aortic valve implantation was identified through a systematic electronic search. A total of 11 publications were identified, describing 16 patients (mean age, 80 years, 65% men). All but 1 patient (94%) received a balloon-expandable valve. All patients received dual antiplatelet therapy immediately following the procedure and continued to take either mono- or dual antiplatelet therapy at the time of valve thrombosis diagnosis. Valve thrombosis was diagnosed at a median of 6 months post-procedure, with progressive dyspnea being the most common symptom. A significant increase in transvalvular gradient (from 10 to 40 mmHg) was the most common echocardiographic feature, in addition to leaflet thickening. Thrombus was not directly visualized with echocardiography. Three patients underwent valve explantation, and the remaining received warfarin, which effectively restored the mean transvalvular gradient to baseline within 2 months. Systemic embolism was not a feature of valve thrombosis post-transcatheter aortic valve implantation. Although a rare, yet likely under-reported complication of post-transcatheter aortic valve implantation, progressive dyspnea coupled with an increasing transvalvular gradient on echocardiography within the months following the intervention likely signifies valve thrombosis. While direct thrombus visualization appears difficult, prompt initiation of oral anticoagulation therapy effectively restores baseline valve function. Copyright © 2014 Karara, H. M. Photogrammetric measurements of the surface topography of the aortic valves obtained from silicon rubber molds of freshly excised human aortic valves are presented. The data are part of an investigation into the design of a new prosthetic valve which will be a central-flow device, like the real valve and unlike previous central-occluding prostheses. Since the maximum stress on the heart valve is induced when the valve is closed and subject to diastolic back-pressure, it was decided to determine the valve geometry during diastole. That is, the molds were formed by pouring the rubber down the excised aortas, causing the valves to close. The molds were made under different pressures (20-120 torr); photogrammetry served as a vehicle for the assessment of the mold topography through the following outputs: digital models, surface profiles, and contour maps. Karara, H. M. Photogrammetric measurements of the surface topography of the aortic valves obtained from silicon rubber molds of freshly excised human aortic valves are presented. The data are part of an investigation into the design of a new prosthetic valve which will be a central-flow device, like the real valve and unlike previous central-occluding prostheses. Since the maximum stress on the heart valve is induced when the valve is closed and subject to diastolic back-pressure, it was decided to determine the valve geometry during diastole. That is, the molds were formed by pouring the rubber down the excised aortas, causing the valves to close. The molds were made under different pressures (20-120 torr); photogrammetry served as a vehicle for the assessment of the mold topography through the following outputs: digital models, surface profiles, and contour maps. Ngow, H A; Wan Khairina, W M N Bacillus cereus endocarditis is rare. It has been implicated in immunocompromised individuals, especially in intravenous drug users as well as in those with a cardiac prosthesis. The patient was a 31-year-old ex-intravenous drug addict with a past history of staphylococcal pulmonary valve endocarditis, who presented with symptoms of decompensated cardiac failure. Echocardiography showed severe aortic regurgitation with an oscillating vegetation seen on the right coronary cusp of the aortic valve. The blood cultures grew Bacillus cereus. We report this as a rare case of Bacillus cereus endocarditis affecting a native aortic valve. Santini, F; Borghetti, V; Amalfitano, G; Mazzucco, A A 73-year old man developed an acute prosthetic aortic valve dehiscence for which emergent operation was undertaken. The intraoperative evidence of an aortic annular disruption and of a subannular abscess led to the hypothesis that an endocarditis process was involved. The aortic valve was replaced with a stentless porcine bioprosthesis. Cultures taken intraoperatively from the aortic area had a pure growth of aerobic, spore-forming, gram-positive bacilli identified as Bacillus licheniformis. The patient responded to specific antibiotic therapy with no relapse at a 20-month follow-up. The potentiality of B. licheniformis as a pathogen should be reconsidered. PMID:8576381 Yip, Cindy Ying Yin; Simmons, Craig A In calcific aortic valve disease, fibrotic and calcific lesions form focally in the fibrosa layer of the valve leaflets. Layer-specific pathosusceptibility suggests that the fibrosa microenvironment is permissive to pathological development. The cellular microenvironment in the aortic valve is defined by a variety of biomechanical-, biochemical-, and extracellular-mediated factors, some of which are unique to the fibrosa. Growing evidence supports the role of these microenvironmental cues in the local regulation of side-specific valve cell phenotypes and focal pathological alterations, revealing new insights into the cellular and molecular processes that contribute to calcific aortic valve disease. Copyright © 2011 Elsevier Inc. All rights reserved. Shadden, Shawn C.; Astorino, Matteo; Gerbeau, Jean-Frédéric In this work we employ a coupled FSI scheme using an immersed boundary method to simulate flow through a realistic deformable, 3D aortic valve model. This data was used to compute Lagrangian coherent structures, which revealed flow separation from the valve leaflets during systole, and correspondingly, the boundary between the jet of ejected fluid and the regions of separated, recirculating flow. Advantages of computing LCS in multi-dimensional FSI models of the aortic valve are twofold. For one, the quality and effectiveness of existing clinical indices used to measure aortic jet size can be tested by taking advantage of the accurate measure of the jet area derived from LCS. Secondly, as an ultimate goal, a reliable computational framework for the assessment of the aortic valve stenosis could be developed. Al-Adhami, Ahmed; Al-Attar, Nawwar Aortic valve replacement is no longer an operation that is approached solely through a median sternotomy. Recent advances in the fields of transcatheter valves have expanded the proportion of patients eligible for intervention. Comparisons between transcatheter valves and conventional surgery have shown non-inferiority of transcatheter valve implants in patients with a high or intermediate pre-operative predictive risk. With advances in our understanding of sutureless valves and their applicability to minimally invasive surgery, the invasiveness and trauma of surgery can be reduced with potential improvements in outcome. The strategy of care has radically changed over the last decade. PMID:27803800 Hamamoto, Masaki; Kobayashi, Taira; Kodama, Hiroshi We describe a new technique of prosthesis-preserving aortic root replacement for patients who have previously undergone aortic valve replacement. With preservation of the mechanical prosthesis, we implant a Gelweave Valsalva graft using double suture lines. The first suture line is made between the sewing cuff of the mechanical valve and the graft, with mattress sutures of 2/0 braided polyester with pledgets. After the first sutures are tied, the second suture line is created between the graft collar and the aortic root remnant with continuous 4/0 polypropylene sutures. Marwan, Mohamed; Achenbach, Stephan Catheter-based aortic valve implantation is increasingly being performed in high-risk patients with symptomatic aortic valve stenosis. For successful planning of the procedure, CT has been shown to provide crucial information concerning the aortic root as well as the peripheral access vessels. This article illustrates the increasing role of CT before transcatheter aortic valve implantation. Kleiman, Neal S.; Reardon, Michael J. Transcatheter aortic valve replacement (TAVR) is becoming widely used for the treatment of symptomatic severe aortic stenosis in patients with high surgical risk. Data from The PARTNER Trial (Placement of AoRtic TraNscathetER Valves) and the Medtronic CoreValve® U.S. Pivotal Investigational Device Exemption trial indicate that survival for extreme-risk patients is superior to best medical therapy and equivalent or superior to surgical aortic valve replacement (SAVR), although long-term durability remains unknown. Paravalvular leak remains higher in TAVR than SAVR, as does permanent pacemaker implantation in self-expanding valves. New-generation valves are addressing these issues, especially for paravalvular leak. There is strong evidence that TAVR is appropriate for both extreme-risk and high-risk patients with symptomatic severe aortic stenosis, and the continued development of new valves are making implantation more reliable. This review discusses the studies supporting the use of TAVR and explores current advances in the field. PMID:27127560 Ren, Xinshuang; Zhang, Minghui; Liu, Kun; Hou, Zhihui; Gao, Yang; Yin, Weihua; Wang, Zhiqiang; Li, Zhennan; Lu, Bin Bicuspid aortic valve (BAV) is a common congenital heart disease. Our study was to analyze clinical features of BAV and evaluate whether aortic valve calcium score (AVCS) was a reliable marker for aortic stenosis (AS) in patients with BAV. 101 patients with BAV who both underwent echocardiology and cardiac computed tomography (CT) scan in our institution were included. Basic clinical data, haemodynamic feature, aortic valve and coronary calcium score were collected and compared among patients with different valve function and different degree of AS. Risk factors related to severe AS were evaluated by logistic regression, and a receiver operative characteristic curve was used to determine the cutoff calcium score greater than which the diagnosis of severe AS was optimized. Patients with aortic regurgitation (AR) were younger and demonstrated larger aortic annulus and sinus compared with patients with other valve dysfunction. Aortic valve calcium score was higher in patients with AS than with AR. For patients with different degree of AS, there were statistical significances in the value of age, aortic valve calcium score and coronary calcium score. AVCS was positively related to severe AS with an odd ratio of 1.286 (95% CI 1.099-1.504) by every 300 points increase. AVCS was also a strong predictor for severe AS with area under the curve 0.855 with a cutoff value of 897 (sensitivity 86.7%, specificity 72.2%). Conclusively, aortic calcium score calculated by quantitative CT is a reliable marker in evaluating severity of AS. Chang, Rei-Yeuh; Chen, Chien-Chang; Hsu, Wei-Pang; Hsiao, Pei-Ching; Tsai, Han-Lin; Hsiao, Ping-Gune; Wu, Jiann-Der; Guo, How-Ran Abstract Background: Avulsion of the aortic valve commissure as a cause of acute aortic valve regurgitation is mostly due to trauma, infective endocarditis, or ascending aortic dissection. Nontraumatic avulsion of the aortic valve commissure is very rare. We reviewed the literature and analyzed potential risk factors of nontraumatic avulsion. Case presentation: An 80-year-old male with hypertension was seen in the emergency department with acute onset dyspnea. Echocardiogram revealed left ventricular hypertrophy with adequate systolic function, prolapse of the noncoronary cusp, and incomplete coaptation of the right coronary and noncoronary cusps with severe aortic valve regurgitation. Surgery revealed an avulsion between the left coronary and noncoronary cusps. Histopathology examination of the aortic valve showed myxoid degeneration, fibrosis, and calcification. Examination of the ascending aorta revealed myxoid degeneration and fragmentation of elastic fibers. Aortic valve replacement was performed, and the patient was alive and well 4 years after surgery. A review of the literature showed that more than three-fourths of the similar cases occurred in males, and about half in patients with hypertension and those 60 years of age or older. Conclusions: In the case of acute aortic regurgitation without a history of trauma, infection, or valvotomy, when 2 prolapsed aortic cusps are observed by echocardiography in the absence of an intimal tear of the ascending aorta, an avulsion of the aortic commissure should be suspected, especially in males with hypertension who are 60 years of age or older. PMID:27749570 Rozeik, Mm; Wheatley, Dj; Gourlay, T The aortic valve operates in a complex haemodynamic environment, opening and closing over 100,000 times a day. When complications arise, such as aortic stenosis, prognosis can be very poor, leading to death within the first few years. Surgical valve replacement is currently the standard treatment for aortic stenosis. A thorough understanding of the anatomy and function of the native valve is imperative when developing a prosthetic replacement that can withstand the complex demands of the heart. This review focuses on the anatomy, structure and disease of the aortic valve and the implications for a transcatheter aortic valve replacement (TAVR). Current complications with TAVR, such as major vascular bleeding, conduction disturbances and patient-prosthesis mismatch (PPM), can be overcome by reducing the delivery profile and through the use of more accurate imaging technologies to work towards a fully functional and durable prosthesis. © The Author(s) 2014. Matsuzaki, Kanji; Unno, Hideya; Konishi, Taisuke; Shigeta, Osamu We report a rare case of left coronary ostial obstruction after aortic valve replacement with a Top Hat supra-annular aortic valve, which was diagnosed with intraoperative transesophageal echocardiography and successfully treated with an unplanned coronary bypass. The patient was a 76-year-old woman (height 143 cm, weight 44 kg) with aortic stenosis and regurgitation. A 19-mm Top Hat valve was implanted in the supra-annular position because of a small aortic annulus. There was a possibility that the high profile of this prosthesis might block the left coronary ostium. There may be a problem with the use of this prosthesis in patients with small and rigid aortic roots with little compliance. Although the Top Hat valve has a great advantage for small aortic annuli, care in its use should be taken due to possible interference with the coronary ostia. Puga, Andrés Enríquez; Rodríguez, Sara Castaño; Pañero, Blanca Mateos; Moreira, Beatriz Castaño; López Almodóvar, Luis Fernando We describe the case of a 61-year-old male with a giant aortic root aneurysm associated with chronic aortic Type A dissection. The patient had been operated on 16 years before due to aortic annuloectasia with mechanical valve replacement. The patient underwent revision aortic surgery with a Bentall-De Bono operation with Svensson modification, using a #21 On-X Valsalva mechanical valve conduit. The postoperative course was uneventful. PMID:28097190 We report a prospective comparison between transcatheter valve implantation (TAVI, n = 13) and surgical aortic valve replacement (AVR, n = 10) in patients with severe aortic valve stenosis and previous coronary bypass surgery (CABG). All patients had at least bilateral patent internal thoracic arteries bypass without indication of repeat revascularization. After a similar post-procedure outcome, despite one early death in TAVI group, the 1-year survival was 100% in surgical group and in transfemoral TAVI group, and 73% in transapical TAVI group. When previous CABG is the lone surgical risk factor, indications for a TAVI procedure have to be cautious, specially if transfemoral approach is not possible. PMID:22642844 Abeyratne, L R; Kingston, J E; Onadim, Z; Dubrey, S W Heritable retinoblastoma is associated with a germline mutation in the tumour suppressor gene RBI. The Rb protein (pRb) arises from the RB1 gene, which was the first demonstrated cancer susceptibility gene in humans. 1 Second primary malignancies are recognised complications of retinoblastoma. Furthermore, pRb is implicated in valve remodelling in calcific aortic valve disease. 2 3 We report a family with hereditary retinoblastoma and associated secondary primary malignancies. There are two interesting aspects to this family. The first is the concept of ‘cancer susceptibility genes’; the RBI gene being the first reported in humans. A further feature of note is that two family members also have bicuspid aortic valves. We discuss a potential association between the gene defect responsible for retinoblastoma (with its associated propensity for further malignancies) and accelerated deterioration of the bicuspid aortic valve in the proband carrying this gene defect. PMID:23595191 Nishida, Hidefumi; Komiya, Tatsuhiko; Sakaguchi, Genichi; Shimamoto, Takeshi The Medtronic freestyle aortic root bioprosthesis (Medtronic, Inc., Minneapolis, MN, USA) is a stentless valve with an effective orifice area that is larger than that observed on other bioprostheses. However, there have been sporadic reports of structural valve deterioration (SVD), such as aortic root wall rupture, leaflet tearing, and pseudoaneurysm formation. We report five cases of SVD of freestyle aortic root bioprostheses. © 2013 The Authors. Journal of Cardiac Surgery Published by Wiley Periodicals, Inc. Careaga-Reyna, Guillermo; Lázaro-Castillo, José Luis; Lezama-Urtecho, Carlos Alberto; Macías-Miranda, Enriqueta; Dosta-Herrera, Juan José; Galván Díaz, José Aortic stenosis is a frequent disease in the elderly, and is associated with other systemic pathologies that may contraindicate the surgical procedure. Another option for these patients is percutaneous aortic valve implantation, which is less invasive. We present our initial experience with this procedure. Patients with aortic stenosis were included once selection criteria were accomplished. Under general anaesthesia and echocardiographic and fluosocopic control, a transcatheter aortic valve was implanted following s valvuloplasty. Once concluded the procedure, angiographic and pressure control was realized in order to confirm the valve function. Between November 2014 and May 2015, 6 patients were treated (4 males and 2 females), with a mean age of 78.83±5.66 years-old. The preoperative transvalvular gradient was 90.16±28.53mmHg and posterior to valve implant was 3.33±2.92mmHg (P<.05). Two patients had concomitant coronary artery disease which had been treated previously. One patient presented with acute right coronary artery occlusion which was immediately treated. However due to previous renal failure, postoperative sepsis and respiratory failure, the patient died one month later. It was concluded that our preliminary results showed that in selected patients percutaneous aortic valve implantation is a safe procedure with clinical improvement for treated patients. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved. Kawashima, Hideyuki; Watanabe, Yusuke; Kozuma, Ken The patient was a 91-year-old woman presenting with severe aortic valve stenosis. Pre-procedural computed tomography scan revealed a 45-mm abdominal aortic aneurysm (AAA). Transfemoral transcatheter aortic valve implantation (TF-TAVI) was performed after endovascular aortic repair (EVAR) of the AAA. The 23-mm Edwards Sapien XT system passed through the aortic stent graft smoothly. This is the first case report showing that successful TF-TAVI can be performed through a prior abdominal aortic stent graft. TF-TAVI after EVAR of AAA is a feasible option for patients with extremely poor access. Kron, Irving L. Patient prosthesis mismatch (PPM) can occur when a prosthetic aortic valve has an effective orifice area (EOA) less than that of a native valve. A recent study by Zorn and colleagues evaluated the incidence and significance of PPM in high risk patients with severe aortic stenosis who were randomized to transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). TAVR is associated with decreased incidence of severe PPM compared to traditional SAVR valves. Severe PPM increases risk for death at 1 year postoperatively in high risk patients. The increased incidence of PPM is largely due to differences in valve design and should encourage development of newer SAVR valves to reduce risk for PPM. In addition more vigorous approaches to root enlargement in small annulus should be performed with SAVR to prevent PPM. PMID:27867654 Ghanta, Ravi K; Kron, Irving L Patient prosthesis mismatch (PPM) can occur when a prosthetic aortic valve has an effective orifice area (EOA) less than that of a native valve. A recent study by Zorn and colleagues evaluated the incidence and significance of PPM in high risk patients with severe aortic stenosis who were randomized to transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). TAVR is associated with decreased incidence of severe PPM compared to traditional SAVR valves. Severe PPM increases risk for death at 1 year postoperatively in high risk patients. The increased incidence of PPM is largely due to differences in valve design and should encourage development of newer SAVR valves to reduce risk for PPM. In addition more vigorous approaches to root enlargement in small annulus should be performed with SAVR to prevent PPM. Yakub, M A; Pau, K K; Awang, Y A minimally invasive approach to aortic valve surgery through a transverse incision ("pocket incision") at the right second intercostal space was examined. Sixteen patients with a mean age of 30 years underwent this approach. The third costal cartilage was either excised (n = 5) or dislocated (n = 11). The right internal mammary artery was preserved. Cardiopulmonary bypass (CPB) was established with aortic-right atrial cannulation in all except the first case. Aortic valve replacements (AVR) were performed in 15 patients and one had aortic valve repair with concomitant ventricular septal defect closure. There was no mortality and no major complications. The aortic cross-clamp, CPB and operative times were 72 +/- 19 mins, 105 +/- 26 mins and 3 hrs 00 min +/- 29 mins respectively. The mean time to extubation was 5.7 +/- 4.0 hrs, ICU stay of 27 +/- 9 hrs and postoperative hospital stay of 5.1 +/- 1.2 days. Minimally invasive "pocket incision" aortic valve surgery is technically feasible and safe. It has the advantages of central cannulation for CPB, preservation of the internal mammary artery and avoiding sternotomy. This approach is cosmetically acceptable and allows rapid patient recovery. Raval, Amish N; Menkis, Alan H; Boughner, Derek R Mitral valve aneurysms are rare complications occurring most commonly in association with aortic valve infective endocarditis. [Decroly 1989, Chua 1990, Northridge 1991, Karalis 1992, Roguin 1996, Mollod 1997, Vilacosta 1997, Cai 1999, Vilacosta 1999, Teskey 1999, Chan 2000, Goh 2000, Marcos- Alberca 2000] While the mechanism of the development of this lesion is unclear, complications such as perforation can occur and lead to significant mitral regurgitation. [Decroly 1989, Karalis 1992, Teskey 1999, Vilacosta 1999]; The case of a 69-year-old male with Streptococcus Sanguis aortic valve endocarditis and associated anterior mitral leaflet aneurysm is presented. Following surgery, tissue pathology of the excised lesion revealed myxomatous degeneration and no active endocarditis or inflammatory cells. This may add support to the hypothesis that physical stress due to severe aortic insufficiency and structural weakening, without infection of the anterior mitral leaflet, can lead to the development of this lesion. Oshima, H; Usui, A; Akita, T; Ueda, Y Aortic valve surgery for the small aortic annulus is still challenging for surgeons. Recently, the new types of high performance prosthesis have been developed and the chance of an aortic root enlargement (ARE) is decreasing. In this study, we propose the ideal strategy of the aortic surgery for the small aortic annulus. We analyzed the clinical records of 158 patients who underwent aortic valve replacement from August 1999 to October 2005 in our institution. The small aortic annulus was observed in 38 patients (24%). Fourteen patients of this group underwent ARE. Patient-prosthesis mismatch (PPM) was less frequently observed in patients with ARE compared to those without ARE. The additional time required for ARE was not considerable, and neither ischemic time nor cardiopulmonary bypass time was significantly prolonged by ARE. In conclusion, we have to select a prosthesis with sufficient orifice area to avoid PPM, otherwise we should choose an option of ARE. For this consideration, we definitely need the chart that demonstrates the relationship between the nominal size of various types of prostheses and the size of a patient's annulus that those prostheses actually fit. Fishbein, Gregory A; Schoen, Frederick J; Fishbein, Michael C Calcific aortic valve disease of the elderly is the most prevalent hemodynamically-significant valvular disease, and the most common lesion requiring valve replacement in industrialized countries. Transcatheter aortic valve implantation is a less invasive alternative to classical aortic valve replacement that can provide a therapeutic option for high-risk or inoperable patients with aortic stenosis. These devices must be biocompatible, have excellent hemodynamic performance, be easy to insert, be securely anchored without sutures, and be durable, without increased risk of thrombosis or infection. To date, complications are related to the site of entry for insertion, the site of implantation (aorta, coronary ostia, base of left ventricle), and to the structure and design of the inserted device. However, as with any novel technology unanticipated complications will develop. Goals for future development will be to make the devices more effective, more durable, safer, and easier to implant, so as to further improve outcome for patients with severe aortic stenosis. The pathologist participating in research and development, and examination of excised devices will have a critical role in improving outcome for these patients. Venardos, Neil; Nadlonek, Nicole A.; Zhan, Qiong; Weyant, Michael J.; Reece, T. Brett; Meng, Xianzhong; Fullerton, David A. Background While calcific aortic stenosis is common, calcification of the other three heart valves is not. The aortic valve interstitial cell (VIC) has been implicated in the pathogenesis of aortic stenosis. Pro-inflammatory stimulation of aortic VICs induces an osteogenic and inflammatory phenotypic change. We hypothesized that the VICs of the other heart valves do not undergo these changes. Using isolated human VICs from normal aortic, mitral, pulmonary and tricuspid valves, our purpose was to compare the osteogenic response to pro-inflammatory stimulation via TLR-4. Materials And Methods Aortic, pulmonic, mitral, and tricuspid (n=4 for each valve type) VICs were isolated from hearts valves explanted from patients undergoing cardiac transplantation. Cells were cultured and grown to confluence in passage 2-6 before treatment with LPS (100-200ng/mL) for 24 or 48 hours. Cells were characterized by immunofluorescent staining. TLR-4 expression was analyzed (immunoblotting, flow cytometry). BMP-2 and intercellular adhesion molecule-1 (ICAM-1) production were determined (immunoblotting). Monocyte chemoattractant protein-1 (MCP-1) levels were determined by ELISA. Statistics were by Mann-Whitney U test. Results TLR-4 stimulation induced BMP-2 production only in aortic VICs (p<0.05). ICAM-1 production and MCP-1 secretion increased in a similar fashion among TLR4-stimulated VICs from all four valves. Conclusions Pro-inflammatory stimulation induces an osteogenic phenotype in aortic VICs but not mitral, pulmonic, or tricuspid VICs. We conclude that this differential osteogenic response of aortic VICs contributes to the pathogenesis of calcific aortic stenosis. PMID:24746950 Berretta, Paolo; Di Eusanio, Marco Aortic valve stenosis is the most common valve disease in the western world. Over the past few years the number of aortic valve replacement (AVR) interventions has increased with outcomes that have been improved despite increasing age of patients and increasing burden of comorbidities. However, despite such excellent results and its well-established position, conventional AVR has undergone great development over the previous two decades. Such progress, by way of less invasive incisions and use of new technologies, including transcatheter aortic valve implantation and sutureless valve prostheses, is intended to reduce the traumatic impact of the surgical procedure, thus fulfilling lower risk patients' expectations on the one hand, and extending the operability toward increasingly high-risk patients on the other. Sutureless and rapid deployment aortic valves are biological, pericardial prostheses that anchor within the aortic annulus with no more than three sutures. The sutureless prostheses, by avoiding the passage and the tying of the sutures, significantly reduce operative times and may improve outcomes. However, there is still a paucity of robust, evidence-based data on the role and performance of sutureless AVR. Therefore, strongest long-term data, randomized studies and registry data are required to adequately assess the durability and long-term outcomes of sutureless aortic valve replacement. PMID:27582765 Roy, James; Manganas, Con; Youssef, George; Rees, David Valve complications following coronary angiography and percutaneous coronary interventions are rare. We report a case of an aortic valve laceration following cardiac catheterization and percutaneous coronary intervention, which required surgical valve replacement. © 2016 Wiley Periodicals, Inc. Mastrobuoni, Stefano; Tamer, Sadallah; de Kerchove, Laurent; El Khoury, Gebrine Aortic valve-sparing procedures are alternative options to aortic valve replacement in patients with aortic root aneurysm and/or severe aortic regurgitation reducing the risk of prosthesis-related complications, such as thromboembolism, and have no need for long-term oral anticoagulation. However, these techniques are technically demanding and long-term results are highly dependent on perfect intraoperative restoration of valve function. We describe a systematic approach to aortic valve-sparing aortic root replacement with the reimplantation technique the way it is currently performed in our institution. Matsuzaki, Kanji; Kudo, Yohei; Ikeda, Akihiko; Konishi, Taisuke; Jikuya, Tomoaki We adopted an anterior longitudinal aortotomy in some cases of aortic valve replacement (AVR), and report them here. The potential of this method is also discussed. We analyzed the data on 24 patients (75.5 ± 7.8 years of age) who had undergone AVR through anterior longitudinal aortotomy. The indications for surgery were prosthetic valve complication in 5 patients, aortic stenosis (AS) with left ventricular outflow tract stenosis (LVOTS) in 16 patients, and aortic regurgitation with moderately dilated ascending aorta in 3 patients. The Konno procedure was performed in 6 cases with small aortic annuli. A longitudinal aortotomy was made at the aortic root along the left side of the right coronary ostium, and extended beyond the right coronary annulus to the interventricular septum as needed. Bioprostheses (21.1 ± 1.7 mm) were used in 23 patients and a 21-mm mechanical valve for one (a 59-year-old man). One high-risk patient died of low output syndrome, leading to a mortality rate of 4.2 %. All other patients recovered well, though atrioventricular block occurred in 2 cases. Anterior longitudinal aortotomy provides a good field of vision at the aortic annulus and the flexibility to develop into anterior annular enlargement. Major indications for this approach are small sino-tubular junction and very small aortic annulus. This approach could be an attractive option in AVR for cases of AS with small aortic annuli and LVOTS. It could also be useful for AVR cases with moderately dilated ascending aorta requiring aortoplasty. Schroeter, T; Subramanian, S; Lehmann, S; Kempfert, J; Misfeld, M; Mohr, F W; Borger, M A In recent years, catheter-based aortic valve interventions have become established procedures for the treatment of high-risk and advanced age patients with aortic valve pathologies. One of the limitations of the widespread applicability of this procedure is the annulus size. Until recently, no prosthesis was available to treat patients with a large annulus. We report on a patient with high-grade aortic stenosis (AS) and a 27-mm annulus, who underwent transapical implantation (TAP) of an Edwards SAPIEN® 29-mm prosthesis (Edwards LifeScience, Irvine, CA, USA). Due to insufficient dilation of his heavily calcified, functionally bicuspid aortic valve leaflets during balloon aortic valvuloplasty (BAV), the TAP prosthesis did not anchor adequately. This was determined during follow-up as he developed progressive aortic insufficiency and orthopnea, and an echocardiography revealed that the valve had been displaced into the LVOT. A conventional aortic valve replacement and ascending aorta replacement were performed, at which time the TAP prosthesis was removed. The patient recovered uneventfully, and was discharged with a well-functioning aortic bioprosthetic valve and in good general condition. © Georg Thieme Verlag KG Stuttgart · New York. Schmitz, Christoph; Sodian, Ralf; Witt, Thomas N; Juchem, Gerd; Lang, Nora; Bruegger, Christian; Kowalski, Christian; Reichart, Bruno Iatrogenic nerve lesions affecting the long thoracic nerve are very rare after a median sternotomy. Here we report on a patient who developed clinical signs of a so-called "winged scapula" after an uneventful aortic valve replacement for infective endocarditis. Bruschi, Giuseppe; DeMarco, Federico; Oreglia, Jacopo; Colombo, Paola; Fratto, Pasquale; Lullo, Francesca; Paino, Roberto; Martinelli, Luigi; Klugmann, Silvio In recent years percutaneous aortic valve implantation has emerged as an alternative therapy to treat patients with symptomatic aortic stenosis considered to be high-risk surgical candidates. We report our experience of a percutaneous retrograde CoreValve implantation in a 77-year-old female with aortic bioprosthesis structural degeneration. The patient underwent aortic valve replacement for aortic stenosis in 1999 with the implantation of a 23 mm Carpentier-Edwards; her last echocardiography showed a severe bioprosthesis stenosis. After evaluation by cardiac surgeons and cardiologist, considering the high risk re-do surgical procedure (Logistic Euroscore 30%) and severe comorbidities (severe pulmonary hypertension, hepatocellular carcinoma and severe osteoporosis), a percutaneous aortic valve-in-valve replacement was preferred. A successful percutaneous 26 mm CoreValve prosthesis implantation was performed with the patient awake with local anesthesia and mild sedation. The patient was discharged after 10 days of hospitalization and she is in NYHA functional class I at follow-up. Our experience, characterized by a multidisciplinary approach, necessary to offer the safest conditions and care for patients, demonstrates the feasibility of a new, promising indication for the use of a transcatheter valve implantation: percutaneous treatment of a degenerated aortic bioprosthesis. Gaede, Luise; Möllmann, Helge Transcatheter aortic valve implantation (TAVI) has evolved as the treatment modality of choice for elderly patients with symptomatic severe aortic stenosis who are at high risk for surgery. More than 10,000 TAVI procedures were undertaken in Germany during 2014.A mortality benefit has been shown for TAVI compared with conservative treatment in patients deemed inoperable, and the procedure was proven to be at least non-inferior to surgical aortic valve replacement in high-risk patients. Through improvements in preprocedural imaging and in valve technology as well as increasing operator and surgical team experience, TAVI has developed rapidly in the past few years. Complication rates declinded considerably and the latest study results even suggest a superiority of TAVI to surgical valve replacement in patients at intermediate operative risk. Nevertheless, the challenge to avoid procedure-specific complications influencing the outcome still remains. Therefore, making an individual decision about the approach and the valve prosthesis in an interdisciplinary heart team consisting of a cardiologist and a cardiac surgeon is indispensable for guaranteeing the best therapy for the patient.Considering the rapid developments and procedural improvements in this field, randomized trials are required to assess whether the indication for TAVI may be extended to patients at lower perioperative risk in the future. Mehta, Sachin; Wilson, Gibbs; Suarez, Keith; Chiles, Christopher D Blunt chest trauma has seldom been reported as a cause of rupture of an aortic valve cusp. We report the case of a 63-year-old man who had a motor vehicle collision resulting in transection of the descending thoracic aorta, splenic pseudoaneurysm, and rupture of an aortic valve cusp causing severe aortic regurgitation. Despite replacement of the aortic valve, he died of multiorgan failure. Wilson, Gibbs; Suarez, Keith; Chiles, Christopher D. Blunt chest trauma has seldom been reported as a cause of rupture of an aortic valve cusp. We report the case of a 63-year-old man who had a motor vehicle collision resulting in transection of the descending thoracic aorta, splenic pseudoaneurysm, and rupture of an aortic valve cusp causing severe aortic regurgitation. Despite replacement of the aortic valve, he died of multiorgan failure. PMID:28670065 Mathieu, Patrick; Boulanger, Marie-Chloé Calcific aortic valve disease (CAVD) is the most common heart valve disorder. There is no medical treatment to prevent and/or promote the regression of CAVD. Hence, it is of foremost importance to delineate and understand the key basic underlying mechanisms involved in CAVD. In the past decade our comprehension of the underpinning processes leading to CAVD has expanded at a fast pace. Hence, our understanding of the basic pathobiological processes implicated in CAVD might lead eventually to the development of novel pharmaceutical therapies for CAVD. In this review, we discuss molecular processes that are implicated in fibrosis and mineralization of the aortic valve. Specifically, we address the role of lipid retention, inflammation, phosphate signalling and osteogenic transition in the development of CAVD. Interplays between these different processes and the key regulation pathways are discussed along with their clinical relevance. Ziakas, Antonios G.; Economou, Fotios I.; Charokopos, Nicholas A.; Pitsis, Antonios A.; Parharidou, Despina G.; Papadopoulos, Thomas I.; Parharidis, Georgios E. Coronary ostial stenosis is a rare but potentially serious sequela after aortic valve replacement. It occurs in the left main or right coronary artery after 1% to 5% of aortic valve replacement procedures. The clinical symptoms are usually severe and may appear from 1 to 6 months postoperatively. Although the typical treatment is coronary artery bypass grafting, patients have been successfully treated by means of percutaneous coronary intervention. Herein, we present the cases of 2 patients in whom coronary ostial stenosis developed after aortic valve replacement. In the 1st case, a 72-year-old man underwent aortic valve replacement and bypass grafting of the saphenous vein to the left anterior descending coronary artery. Six months later, he experienced a non-ST-segment-elevation myocardial infarction. Coronary angiography revealed a critical stenosis of the right coronary artery ostium. In the 2nd case, a 78-year-old woman underwent aortic valve replacement and grafting of the saphenous vein to an occluded right coronary artery. Four months later, she experienced unstable angina. Coronary angiography showed a critical left main coronary artery ostial stenosis and occlusion of the right coronary artery venous graft. In each patient, we performed percutaneous coronary intervention and deployed a drug-eluting stent. Both patients were asymptomatic on 6-to 12-month follow-up. We attribute the coronary ostial stenosis to the selective ostial administration of cardioplegic solution during surgery. We conclude that retrograde administration of cardioplegic solution through the coronary sinus may reduce the incidence of postoperative coronary ostial stenosis, and that stenting may be an efficient treatment option. PMID:20844624 Hatori, Kyohei; Ohki, Satoshi; Obayashi, Tamiyuki; Koyano, Tetsuya; Yasuhara, Kiyomitsu; Hirai, Hanako We describe the case of an 82-year-old woman who had undergone aortic mechanical valve replacement for aortic stenosis with a small annulus, and coronary artery bypass grafting. Four years after the operation, she began to experience hemolysis. Prosthetic valve obstruction was observed but there was no paravalvular leakage or aortic regurgitation through the mechanical valve. We elected to perform apicoaortic bypass in this patient with severe hemolytic anemia secondary to a mechanical valve malfunction. Chhatriwalla, Adnan K; Allen, Keith B; Saxon, John T; Cohen, David J; Aggarwal, Sanjeev; Hart, Anthony J; Baron, Suzanne J; Dvir, Danny; Borkon, A Michael Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) may be less effective in small surgical valves because of patient/prosthesis mismatch. Bioprosthetic valve fracture (BVF) using a high-pressure balloon can be performed to facilitate VIV TAVR. We report data from 20 consecutive clinical cases in which BVF was successfully performed before or after VIV TAVR by inflation of a high-pressure balloon positioned across the valve ring during rapid ventricular pacing. Hemodynamic measurements and calculation of the valve effective orifice area were performed at baseline, immediately after VIV TAVR, and after BVF. BVF was successfully performed in 20 patients undergoing VIV TAVR with balloon-expandable (n=8) or self-expanding (n=12) transcatheter valves in Mitroflow, Carpentier-Edwards Perimount, Magna and Magna Ease, Biocor Epic and Biocor Epic Supra, and Mosaic surgical valves. Successful fracture was noted fluoroscopically when the waist of the balloon released and by a sudden drop in inflation pressure, often accompanied by an audible snap. BVF resulted in a reduction in the mean transvalvular gradient (from 20.5±7.4 to 6.7±3.7 mm Hg, P<0.001) and an increase in valve effective orifice area (from 1.0±0.4 to 1.8±0.6 cm(2), P<0.001). No procedural complications were reported. BVF can be performed safely in small surgical valves to facilitate VIV TAVR with either balloon-expandable or self-expanding transcatheter valves and results in reduced residual transvalvular gradients and increased valve effective orifice area. © 2017 American Heart Association, Inc. Itagaki, Shinobu; Chikwe, Joanna P; Chiang, Yuting P; Egorova, Natalia N; Adams, David H Bicuspid aortic valves are associated with valve dysfunction, ascending aortic aneurysm and dissection. Management of the ascending aorta at the time of aortic valve replacement (AVR) in these patients is controversial and has been extrapolated from experience with Marfan syndrome, despite the absence of comparative long-term outcome data. This study sought to assess whether the natural history of thoracic aortopathy after AVR in patients with bicuspid aortic valve disease is substantially different from that seen in patients with Marfan syndrome. In this retrospective comparison, outcomes of 13,205 adults (2,079 with bicuspid aortic valves, 73 with Marfan syndrome, and 11,053 control patients with acquired aortic valve disease) who underwent primary AVR without replacement of the ascending aorta in New York State between 1995 and 2010 were compared. The median follow-up time was 6.6 years. The long-term incidence of thoracic aortic dissection was significantly higher in patients with Marfan syndrome (5.5 ± 2.7%) compared with those with bicuspid valves (0.55 ± 0.21%) and control group patients (0.41 ± 0.08%, p < 0.001). Thoracic aortic aneurysms were significantly more likely to be diagnosed in late follow-up in patients with Marfan syndrome (10.8 ± 4.4%) compared with those with bicuspid valves (4.8 ± 0.8%) and control group patients (1.4 ± 0.2%) (p < 0.001). Patients with Marfan syndrome were significantly more likely to undergo thoracic aortic surgery in late follow-up (10.4 ± 4.3%) compared with those with bicuspid valves (2.5 ± 0.6%) and control group patients (0.50 ± 0.09%) (p < 0.001). The much higher long-term rates of aortic complications after AVR observed in patients with Marfan syndrome compared with those with bicuspid aortic valves confirm that operative management of patients with bicuspid aortic valves should not be extrapolated from Marfan syndrome and support discrete treatment algorithms for these different clinical entities Bombien Quaden, René; Leester-Schaedel, Monika; Lozonschi, Lucian; Lutter, Georg The resection of pulmonary valves has already been demonstrated in an experimental beating-heart model. The aim of this study was to analyse the transapical laser-assisted resection of aortic valves in an in vivo porcine model in a non-beating heart. The resection was performed in a porcine model (n = 10) using a Thullium:YAG laser. After establishing a standard extracorporeal circulatory support, the aortic valve isolation chamber (AVIC) system was inserted transapically. The resection of the aortic leaflets was carried out step-by-step in the arrested heart. The AVIC implantation, the resection process, and the gross anatomy of intracardiac lesions were analysed. The procedure for installing the AVIC took 5.8 ± 1.5 min. A sealed chamber was achieved in 9/10 cases. The resection of the valves was performed in 8/10 and completed in 7/10 cases. The resection took, on average, 7.4 ± 2.7 min/cusp. In 9/10 cases, the sealing was sufficient. Gross anatomy and histological analysis demonstrated only superficial damage to the surrounding tissue. In this study, the in vivo on-pump isolation of the left ventricular outflow tract and the laser resection of the native aortic valve could be demonstrated successfully. Nevertheless, this model is the next step towards a beating-heart resection of the aortic valve using the isolation chamber. Patients with a bicuspid aortic valve (BAV) constitute a heterogeneous population with variable clinical presentation and complications. More than 50% of the patients who require aortic valve replacement have a BAV, a condition that may be associated with dilation of ascending aorta and aortic insufficiency caused by cusp disease or aortic root pathology. Of the potential BAV-related complications, dilation of the aortic root and ascending aorta are among the most serious. The dilation of ascending aorta and aortic root have been the subject of controversy. Whereas some surgeons believe that the dilation of the aorta is caused by the hemodynamic properties of the BAV, others believe that the dilation of the aortic root is secondary to genetic defects associated with the BAV. Management of a BAV should be tailored to each patient's clinical condition. The surgical approach varies from aortic valve replacement to combined aortic valve and root replacement to aortic-valve-sparing root replacement. Gorczynski, A; Trenkner, M; Anisimowicz, L; Gutkowski, R; Drapella, A; Kwiatkowska, E; Dobke, M Pulmonary autograft valve replacement has been simulated by implanting the pulmonary valve into the aortic position of the same cadaver heart from both human and porcine sources. The forces acting on the pulmonary valve leaflets have been calculated on the basis of a triaxial ellipsoid mathematical model. These forces on the pulmonary autograft valve were shown to be essentially similar to those previously reported for aortic valve leaflets. Biomechanical measurements have been made on the simulated autograft valves and on the isolated pulmonary valve cusps. The tensile strengths of the pulmonary valve cusps in both circumferential and radial directions were roughly three times greater than those of aortic valve cusps. This indicated the ability of the pulmonary valves to accept, ab initio, aortic valve closing pressures. Pressure-induced changes in dimension, calculated on the basis of diameters of the simulated pulmonary autograft root, also indicated that the distensibility of the autograft valve was limited. It reached a maximum at 30 mm Hg (4 kPa) without any suggestion of further distension to the point of distortion and incompetence. The combination of the calculated forces acting on the valve and the biomechanical measurements have shown that pulmonary valves used as autograft aortic valve replacements are able to tolerate aortic pressures from the time of implantation. These experimental results from simulated autografts support the clinical use of this valve over the past 13 years. PMID:7135295 Salem, B I; Pechacek, L W; Leachman, R D A 21-year-old man had acute aortic insufficiency three months after insertion of an aortic valve prosthesis. Chest roentgenography demonstrated abnormal orientation of the prosthesis. M-mode echocardiography showed dense, linear echoes from the prosthetic valve between the interventricular septum and the mitral valve, along with loss of normal poppet motion within the aortic root. At surgery, the prosthesis was found to be extensively disrupted, resulting in prolapse into the left ventricular outflow tract. Another valve replacement was performed with patient survival. Echocardiography appears to be a useful adjunct to established roentgenographic procedures in the diagnosis of major dehiscence of prosthetic aortic valves. Acharya, Asha; Hans, Chetan P; Koenig, Sara N; Nichols, Haley A; Galindo, Cristi L; Garner, Harold R; Merrill, Walter H; Hinton, Robert B; Garg, Vidu Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD) are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs). We found significant downregulation of Sox9 along with several cartilage-specific genes that were direct targets of the transcription factor, Sox9. Loss of Sox9 expression has been published to be associated with aortic valve calcification. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, the addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism. Mohammadi, Hadi; Mequanint, Kibret Although heart valve replacement is among the most common cardiovascular surgical procedures, their outcome is often difficult to predict. One of the reasons is the design and choice of the materials used for the fabrication of the prostheses. This review paper describes the use of modeling techniques in prosthetic heart valve (HV) design and aims at the justification and development of a polymer based trileaflet mechanical heart valve (MHV). The closing/opening phase behavior of the bileaflet MHV was investigated. The potential problem of valve failure due to crack propagation in the brittle pyrolytic carbon leaflet was also discussed. These studies suggest that although bileaflet MHV performs satisfactorily, there are justifications for improvement. Since the native aortic HV is trileaflet and made of anisotropic and hyperelastic tissue, one possible approach to a better MHV design is based on our ability to closely mimic the natural geometry and biomaterial properties. Kazama, S; Kurata, A; Yamashita, Y An aortic valve replacement was successfully performed employing the Nicks annulus enlargement procedure in a case of aortic valve stenosis with small annulus 12 years after mitral valve replacement. Previous mitral valve replacement does not preclude feasibility of the Nicks procedure. Chain, Sergio; Luciardi, Hector; Feldman, Gabriela; Berman, Sofia; Estrella, Cristina Nocardia endocarditis in native valve is an uncommon infection that usually arises in immunodepressed patients. We report a 51-year-old man diagnosed as having Nocardia endocarditis in aortic and tricuspid native valves, which received antimicrobial therapy and required aortic valve replacement. In 6 month follow up the patient remained asymptomatic with good clinical evolution. Makkar, Raj R; Fontana, Gregory P; Jilaihawi, Hasan; Kapadia, Samir; Pichard, Augusto D; Douglas, Pamela S; Thourani, Vinod H; Babaliaros, Vasilis C; Webb, John G; Herrmann, Howard C; Bavaria, Joseph E; Kodali, Susheel; Brown, David L; Bowers, Bruce; Dewey, Todd M; Svensson, Lars G; Tuzcu, Murat; Moses, Jeffrey W; Williams, Matthew R; Siegel, Robert J; Akin, Jodi J; Anderson, William N; Pocock, Stuart; Smith, Craig R; Leon, Martin B Transcatheter aortic-valve replacement (TAVR) is the recommended therapy for patients with severe aortic stenosis who are not suitable candidates for surgery. The outcomes beyond 1 year in such patients are not known. We randomly assigned patients to transfemoral TAVR or to standard therapy (which often included balloon aortic valvuloplasty). Data on 2-year outcomes were analyzed. A total of 358 patients underwent randomization at 21 centers. The rates of death at 2 years were 43.3% in the TAVR group and 68.0% in the standard-therapy group (P<0.001), and the corresponding rates of cardiac death were 31.0% and 62.4% (P<0.001). The survival advantage associated with TAVR that was seen at 1 year remained significant among patients who survived beyond the first year (hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.92; P=0.02 with the use of the log-rank test). The rate of stroke was higher after TAVR than with standard therapy (13.8% vs. 5.5%, P=0.01), owing, in the first 30 days, to the occurrence of more ischemic events in the TAVR group (6.7% vs. 1.7%, P=0.02) and, beyond 30 days, to the occurrence of more hemorrhagic strokes in the TAVR group (2.2% vs. 0.6%, P=0.16). At 2 years, the rate of rehospitalization was 35.0% in the TAVR group and 72.5% in the standard-therapy group (P<0.001). TAVR, as compared with standard therapy, was also associated with improved functional status (P<0.001). The data suggest that the mortality benefit after TAVR may be limited to patients who do not have extensive coexisting conditions. Echocardiographic analysis showed a sustained increase in aortic-valve area and a decrease in aortic-valve gradient, with no worsening of paravalvular aortic regurgitation. Among appropriately selected patients with severe aortic stenosis who were not suitable candidates for surgery, TAVR reduced the rates of death and hospitalization, with a decrease in symptoms and an improvement in valve hemodynamics that were sustained at 2 years of Sievers, Hans H At first glance the aortic valve is a relative simple valve mechanism connecting the left ventricle and the ascending aorta. Detailed analysis of the different components of the aortic valve including the leaflets and sinuses revealed a complex motion of each part leading to a perfect durable valve mechanism at rest and during exercise. Theoretically, the reconstruction or imitation of these structures in patients with aortic valve disease should lead to optimal results. Prerequisite is the exact knowledge of the important functional characteristics of the aortic valve. The dynamic behavior of the aortic root closely harmonizing with the leaflets not only warrants stress minimizing and valve durability, but also optimizes coronary flow, left ventricular function and aortic impedance. The newly discovered contractile capacity of the leaflets and the root components are important for tuning the dynamics. Isolated reconstruction of the aortic valve such as decalcification, commissurotomy, plication of ring or leaflets of a tricuspid aortic valve and cusp extension are seldom indicated in contrast to the reconstruction of the bicuspid insufficient valve. Proper indication and skilled techniques lead to excellent hemodynamic and clinical intermediate-term result up to 7 years after reconstruction. Latest follow-up revealed a mean aortic insufficiency of 0.7, maximal pressure gradient of 11.4 +/- 8.5 mm Hg with zero hospital or late mortality, reoperation or thromboembolic events in 22 patients. The reconstructive techniques for aortic root aneurysm and/or type A dissection according to David or Yacoub have become routine procedures in the last 10 years. The hemodynamic and clinical results are excellent with low reoperation rate and very low risk of thromboembolism. Generally, a maximal diameter of the root of 5 cm is indicative for performing the operation. In patients with Marfan's syndrome the reconstruction should be advanced even with smaller diameters especially Pine, M; Hahn, G; Paton, B; Pappas, G; Davies, H; Steele, P; Pryor, R; Blount, S G Homograft aortic valve replacement was done in 103 patients and prosthetic aortic valve replacement in 106 between January 1962 and December 1973. Patients who received homograft and prosthetic valves were compared with respect to age, sex, preoperative functional impairment, infection, dyspnea, angina, hemodynamics, chest X-ray, electrocardiogram, associated operations, early and late mortality, and valve failure. Combined total mortality was 28% (12% operative, 8% first postoperative year, 8% late). Ten percent of valve required replacement. One year after operation, 70% of survivors were asymptomatic, 27% were improved, and 3% were unchanged or between homograft and prosthetic valve replacement. Valve-related failure and infections were more common after homograft aortic valve replacement. Emboli, hemorrhage, and hemolysis were commoner after prosthetic valve replacement. Fungal infections occurred in five homograft patients but in no patient with a prosthetic aortic valve. Severe properative symptoms or recent endocarditis was associated with greater mortality and valve failure in both the homograft and the prosthetic series. Increased mortality and failure was also seen in patients with either preoperative aortic regurgitation with high left ventricular end-diastolic pressure and low cardiac index, or aortic stenosis with cardiomegaly or roentgenographic evidence of congestive heart failure. Therefore, in two series of patients at equal risk, mortality and valve failure were similar for homograft and prosthetic aortic valve replacement. di Summa, Michele; Iezzi, Federica Fibroelastomas account for less than 10% of all cardiac tumours, representing the most common valvular and the second most common cardiac benign tumour, following myxomas. Fibroelastomas are histologically benign; they can result in life-threatening complications such as stroke, acute valvular dysfunction, embolism, ventricular fibrillation, and sudden death. Surgical resection should be offered to all patients who have symptoms and to asymptomatic patients who have pedunculated lesions or tumors larger than 1 cm in diameter. Valve-sparing excision produces good long-term results in most instances. We report our surgical experience of a giant fibroelastoma in the aortic valve. Kostina, Aleksandra S; Uspensky, Vladimir Е; Irtyuga, Olga B; Ignatieva, Elena V; Freylikhman, Olga; Gavriliuk, Natalia D; Moiseeva, Olga M; Zhuk, Sergey; Tomilin, Alexey; Kostareva, Аnna А; Malashicheva, Anna B Bicuspid aortic valve is the most common congenital heart malformation and the reasons for the aortopathies associated with bicuspid aortic valve remain unclear. NOTCH1 mutations are associated with bicuspid aortic valve and have been found in individuals with various left ventricular outflow tract abnormalities. Notch is a key signaling during cardiac valve formation that promotes the endothelial-to-mesenchymal transition. We address the role of Notch signaling in human aortic endothelial cells from patients with bicuspid aortic valve and aortic aneurysm. Aortic endothelial cells were isolated from tissue fragments of bicuspid aortic valve-associated thoracic aortic aneurysm patients and from healthy donors. Endothelial-to-mesenchymal transition was induced by activation of Notch signaling. Effectiveness of the transition was estimated by loss of endothelial and gain of mesenchymal markers by immunocytochemistry and qPCR. We show that aortic endothelial cells from the patients with aortic aneurysm and bicuspid aortic valve have down regulated Notch signaling and fail to activate Notch-dependent endothelial-to-mesenchymal transition in response to its stimulation by different Notch ligands. Our findings support the idea that bicuspid aortic valve and associated aortic aneurysm is associated with dysregulation of the entire Notch signaling pathway independently on the specific gene mutation. Berfield, Kathleen K S; Sweet, Matthew P; McCabe, James M; Reisman, Mark; Mackensen, G Burkhard; Mokadam, Nahush A; Dean, Larry S; Smith, Jason W Transcatheter aortic valve replacement is being used with increasing frequency in patients with severe aortic stenosis who are otherwise deemed to be at high surgical risk. Aortic dissection is a rare complication of transcatheter aortic valve replacement and poses a unique management dilemma. We describe the treatment of an acute Stanford type A aortic dissection after transcatheter aortic valve replacement with a modified thoracic endovascular stent graft in a 95-year-old woman. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved. Misenheimer, Jacob A.; Ramaraj, Radhakrishnan Aortic stenosis is the most common valvular heart disease in the developed world. About 7% of the population over age 65 years suffers from degenerative aortic stenosis. The prognosis of patients with symptomatic severe aortic stenosis is dismal without valve replacement. Even though the American College of Cardiology recommends aortic valve replacement to treat this condition as a class I recommendation, approximately one third of these patients over the age of 75 years are not referred for surgery. Typically, this is from concern about prohibitive surgical risk associated with patient frailty, comorbidities, age, and severe left ventricular dysfunction. The advent in France of transcatheter aortic valve replacement has raised the hope in the United States for an alternative, less invasive treatment for aortic stenosis. Two recent trials—the Placement of AoRTic TraNscathetER Valve Trial Edwards SAPIEN Transcatheter Heart Valve (Partner) and the CoreValve US Pivotal—have established transcatheter aortic valve replacement as the preferred approach in patients who are at high or prohibitive surgical risk. The more recently published Partner 2 trial has shown the feasibility of transcatheter aortic valve replacement in intermediate-surgical-risk patients as well. With a profile that promises easier use and better valve performance and delivery, newer-generation valves have shown their potential for further improvement in safety profile and overall outcomes. We review the history and status of this topic. PMID:28265210 Lotfi, Shahram; Dohmen, Guido; Götzenich, Andreas; Haushofer, Marcus; Spillner, Jan Wilhelm; Autschbach, Rüdiger; Hoffmann, Rainer Transcatheter aortic valve implantation (TAVI) has become a therapeutic option for high-risk or nonoperable patients with severe symptomatic aortic valve stenosis. The best known and most frequently implanted prostheses are the CoreValve and SAPIEN prostheses. We report our experiences and analyze the results of our TAVI program. A total of 357 patients underwent transfemoral (TF) and transapical (TA) TAVI in our center between January 2008 and October 2012. The procedure was performed in 190 patients with CoreValve, in 155 patients with SAPIEN, and in 12 patients with ACURATE TA prostheses. Transfemoral access was used in 190 patients. In 167 patients, TA access was used. The mean age was 80.2 ± 6.4 years. All patients were nonoperable or had a high risk for a conventional aortic valve replacement. The mean logistic EuroSCORE I was 25.92 ± 14.51%. The TF/CoreValve (190 patients) and TA/SAPIEN (155 patients) groups showed significant difference in the patients' mean age (81.7 ± 6.3 years vs. 79.5 ± 6.6 years, P = 0.002) and in mean logistic EuroSCORE I (22.16 ± 13.05% vs. 31.04 ± 16.40, P < 0.001). The overall 30-day mortality (357 patients) was 9.80% (TF, 8.42%; TA, 11.37%); overall 1-year mortality (275 patients), 21.45% (TF, 23.74%; TA, 19.12%); overall 2-year mortality (199 patients), 29.15% (TF, 35.96%; TA, 23.64%); overall 3-year mortality (133 patients), 37.59% (TF, 43.86%; TA, 32.89%); and overall 4-year mortality (38 patients), 39.47% (TF, 45%; TA, 33.33%). The rate of pacemaker implantation after TAVI was significantly higher in the CoreValve group than in the SAPIEN group: 44.74% (85/190 patients) versus 6.45% (10/155 patients), P < 0.001. Stroke rate was higher in the TF-CoreValve group than in the TA-SAPIEN group: 4.21% versus 0.64%, P = 0.045. Outcomes after TAVI were, in our population of nonoperable and high-risk patients, encouraging. The differences in midterm outcomes between the TF-CoreValve TAVI and the TA-SAPIEN TAVI were not significant. Kunitomo, Ryuji; Okamoto, Ken; Moriyama, Shuji; Sakaguchi, Hisashi; Tazume, Hirokazu; Yoshinaga, Takashi; Kawasuji, Michio The damage to the intervalvular fibrous trigone (IVFT) by infective endocarditis makes combined aortic and mitral valve replacement difficult. We performed Manouguian's double valve replacement for such a case and obtained a good result. A 81-year-old male underwent emergency operation due to active prosthetic valve endocarditis. He had a history of receiving combined aortic and mitral valve replacement because of active infective endocarditis at the age of 74 and redo aortic valve replacement 3 years after that. The infectious lesion extended from the mitral annulus to the IVFT and the aortic annulus, and it caused the prosthetic valve detachment from the aortic annulus. Manouguian's double valve replacement was required for radical resection and reconstruction of the IVFT. No recurrent infection or paravalvular leakage was observed during 49months follow up period. Manouguian's procedure is useful for complete resection of the infected IVFT and makes combined aortic and mitral valve replacement safer. Pascual, Isaac; Carro, Amelia; Hernández-Vaquero, Daniel; Díaz, Rocío; Rozado, Jose; Lorca, Rebeca; Martín, María; Silva, Jacobo; Morís, César Transcatheter aortic valve implantation (TAVI) is a rapidly evolving therapeutic modality currently available for patients with severe aortic stenosis (AS) that are unsuitable for surgery because of technical/anatomical issues or high-estimated surgical risk. Transfemoral approach is the preferred TAVI delivery route when possible. Alternative non-transfemoral access options include transaortic, trans-subclavian and transapical access. Other approaches are also feasible (transcarotid, transcaval, and antegrade aortic) but are restricted to operators and hospitals with experience. The peculiarities of each of the vascular approaches designed for TAVI delivery make it necessary to carefully assess patient’s atherosclerotic load and location, arterial size and tortuosity, and presence of mural thrombus. Several clinical trials are currently ongoing and in the near future the indications for these approaches will likely be better defined and extended to a broader spectrum of TAVI candidates. PMID:28616344 Bertsch, Elizabeth C; Minturn, Lucy; Gotteiner, Nina L; Ernst, Linda M A 20-week-old fetus with the 22q11.2 deletion characteristic of DiGeorge syndrome is described with vertebral segmentation abnormalities and complex cardiovascular anomalies including an absent aortic valve. This is only the second known case of absent aortic valve in association with DiGeorge syndrome. We discuss the association of absent aortic valve with other conotruncal defects and the utility of fetal echocardiography in the diagnosis of DiGeorge syndrome. Purpose: Over the past 30 years there have been experimental efforts at catheter-based management of aortic valve regurgitation with the idea of extending treatment to nonsurgical candidates. A new catheter-based aortic valve design is described.Methods: The new catheter-delivered valve consists of a stent-based valve cage with locking mechanism and a prosthetic flexible tilting valve disc. The valve cage is delivered first followed by deployment and locking of the disc. In acute experiments, valve implantation was done in four dogs.Results: Valve implantation was successful in all four animals. The implanted valve functioned well for the duration of the experiments (up to 3 hr).Conclusion: The study showed the implantation feasibility and short-term function of the tested catheter-based aortic disc valve. Further experimental studies are warranted. Gould, Sarah T; Srigunapalan, Suthan; Simmons, Craig A; Anseth, Kristi S This review highlights aspects of calcific aortic valve disease that encompass the entire range of aortic valve disease progression from initial cellular changes to aortic valve sclerosis and stenosis, which can be initiated by changes in blood flow (hemodynamics) and pressure across the aortic valve. Appropriate hemodynamics is important for normal valve function and maintenance, but pathological blood velocities and pressure can have profound consequences at the macroscopic to microscopic scales. At the macroscopic scale, hemodynamic forces impart shear stresses on the surface of the valve leaflets and cause deformation of the leaflet tissue. As discussed in this review, these macroscale forces are transduced to the microscale, where they influence the functions of the valvular endothelial cells that line the leaflet surface and the valvular interstitial cells that populate the valve extracellular matrix. For example, pathological changes in blood flow-induced shear stress can cause dysfunction, impairing their homeostatic functions, and pathological stretching of valve tissue caused by elevated transvalvular pressure can activate valvular interstitial cells and latent paracrine signaling cytokines (eg, transforming growth factor-β1) to promote maladaptive tissue remodeling. Collectively, these coordinated and complex interactions adversely impact bulk valve tissue properties, feeding back to further deteriorate valve function and propagate valve cell pathological responses. Here, we review the role of hemodynamic forces in calcific aortic valve disease initiation and progression, with focus on cellular responses and how they feed back to exacerbate aortic valve dysfunction. Sanchez, Pedro L; Mazzone, Anna Maria Aortic Valve Disease, includes a range of disorder severity from mild leaflet thickening without valve obstruction, "aortic sclerosis", to severe calcified aortic stenosis. It is a slowly progressive active process of valve modification similar atherosclerosis for cardiovascular risk factors, lipoprotein deposition, chronic inflammation, and calcification. Systemic signs of inflammation, as wall and serum CRP, similar to those found in atherosclerosis, are present in patients with degenerative aortic valve stenosis and may be expression of a common disease, useful in monitoring of stenosis progression. PMID:17042945 Bradley, Scott M The contents of this article were presented in the session "Aortic insufficiency in the teenager" at the congenital parallel symposium of the 2013 Society of Thoracic Surgeons (STS) annual meeting. The accompanying articles detail the approaches of aortic valve repair and the Ross procedure.(1,2) The current article focuses on prosthetic valve replacement. For many young patients requiring aortic valve surgery, either aortic valve repair or a Ross procedure provides a good option. The advantages include avoidance of anticoagulation and potential for growth. In other patients, a prosthetic valve is an appropriate alternative. This article discusses the current state of knowledge regarding mechanical and bioprosthetic valve prostheses and their specific advantages relative to valve repair or a Ross procedure. In current practice, young patients requiring aortic valve surgery frequently undergo valve replacement with a prosthetic valve. In STS adult cardiac database, among patients ≤30 years of age undergoing aortic valve surgery, 34% had placement of a mechanical valve, 51% had placement of a bioprosthetic valve, 9% had aortic valve repair, and 2% had a Ross procedure. In the STS congenital database, among patients 12 to 30 years of age undergoing aortic valve surgery, 21% had placement of a mechanical valve, 18% had placement of a bioprosthetic valve, 30% had aortic valve repair, and 24% had a Ross procedure. In the future, the balance among these options may be altered by design improvements in prosthetic valves, alternatives to warfarin, the development of new patch materials for valve repair, and techniques to avoid Ross autograft failure. Bruschi, Giuseppe; Colombo, Paola; Botta, Luca; Nava, Stefano; Merlanti, Bruno; Belli, Oriana; Musca, Francesco; Soriano, Francesco; Russo, Claudio F; Oliva, Fabrizio Transcatheter aortic valve implantation has been designed to treat older patients affected by severe aortic stenosis who are considered high-risk surgical candidates because of multiple comorbidities. The least invasive approach for transcatheter aortic valves implantation should be considered the transfemoral retrograde route, because it is minimally invasive and is feasible with local anesthesia and mild sedation. Despite significant technical improvements in recent years, the transfemoral approach is contraindicated in cases of severe peripheral artery disease. We describe the first case of a Portico transcatheter aortic valve implantation system (St. Jude Medical, Minneapolis, MN) made through the distal axillary artery in a 90-year-old patient affected by severe aortic stenosis. Mahesh, Balakrishnan; Deville, Claude; Nashef, Samer Valve-sparing aortic root replacement (ARR) is the procedure of choice in young patients with aortic root aneurysm and preserved aortic valve leaflets; however, coronary ostial anastomoses remain an issue. Troublesome bleeding sometimes occurs during surgery, and in the long term, there is a risk of aneurysmal formation in the residual aortic wall of the ostial "button." We describe a technique of valve-sparing ARR wherein each coronary button along with its flange of aortic tissue is implanted within the prosthetic graft used for ARR, thereby eliminating the risk of both immediate surgical bleeding and late coronary button aneurysms. Kiyota, Yuka; Della Corte, Alessandro; Montiero Vieira, Vanessa; Habchi, Karam; Huang, Chuan-Chin; Della Ratta, Ester E; Sundt, Thoralf M; Shekar, Prem; Muehlschlegel, Jochen D; Body, Simon C Objective Patients with structural abnormalities of cardiac valves, including bicuspid aortic valve (BAV), are said to be at higher risk of infective endocarditis (IE). We sought to determine the risk of IE of the BAV compared with the tricuspid aortic valve (TAV) and to determine the risk of aortic valve replacement and mortality after IE. Methods From medical records of two US and one Italian hospitals, patients with their first episode of IE of any native valve were identified. In the US cohort 42 patients with BAV and 393 patients with TAV with IE occurring between 1 January 2000 and 30 June 2014 were identified. In the Italian cohort 48 patients with BAV and 341 patients with TAV with IE underwent valve replacement surgery between 1 January 2000 and1 November 2015. The risk of IE for BAV and TAV and subsequent outcomes were determined after matching to patients without IE. Results After adjustment for risk factors, the risk of IE in the US cohort was 23.1 (95% CI 8.1 to 100, p <0.0001) times greater for BAV than TAV. Patients with BAV with IE were more likely to have an aortic root abscess. Within the subsequent 5 years, BAV patients with IE were more likely to undergo valve replacement (85%) than TAV patients with IE (46%). Patients with IE were at increased risk of death. The findings were similar in the Italian cohort. Conclusions Patients with BAV are at markedly increased risk of IE and aortic root abscess than patients with TAV. Increased risk of IE in patients with BAV indicates they may be a candidate group for long-term trials of antibiotic prophylaxis of IE. PMID:28674620 Swinkels, B M; Jaarsma, W; Wely, L Relik-van; van Swieten, H A; Ernst, J M P G; Plokker, H W M This case report describes a patient with severe calcific aortic stenosis who was initially considered inoperable because of a very poor left ventricular function and severe pulmonary hypertension. After balloon aortic valvuloplasty, the clinical and haemodynamic status of the patient improved to such an extent that subsequent aortic valve replacement was considered possible and eventually proved to be successful. Balloon aortic valvuloplasty has value as a potential bridge to aortic valve replacement when the risks for surgery are considered to be too high. Wilbring, Manuel; Tugtekin, Sems Malte; Matschke, Klaus; Kappert, Utz We report the clinical course of a patient with a history of transapical aortic "valve-in-valve" transcatheter aortic valve implantation (TAVI), actually suffering from prosthetic valve endocarditis. The patient now underwent cardiac surgery as a salvage procedure. The procedure itself was uneventful, but the patient died several days postoperative due to persisting sepsis. The present case raises the question, how to deal with high-risk patients, once considered unsuitable for cardiac surgery in presence of prosthetic valve infection? Up to now, there exists only insufficient knowledge about incidence, clinical course, and effectiveness of treatment strategies for prosthetic valve endocarditis after TAVI. A review of the available literature is given. Georg Thieme Verlag KG Stuttgart · New York. Julien, Maureen B; Desai, Nimesh; Brozena, Susan; Herrmann, Howard C Despite the widespread use of transcatheter aortic valve replacement (TAVR) for moderate and high-risk patients with severe aortic stenosis, it is utilized less frequently in patients with bicuspid aortic valves (BAV). Orthotopic heart transplant (OHT) donors tend to be younger and may have undiagnosed BAV. We present a case of successful TAVR in a patient with BAV thirteen years after OHT. van Rensburg, Annari; Doubell, Anton The therapeutic implications of bicuspid aortic valve associations have come under scrutiny in the transcatheter aortic valve implantation era. We evaluate the spectrum of mitral valve disease in patients with bicuspid aortic valves to determine the need for closer echocardiographic scrutiny/follow-up of the mitral valve. A retrospective analysis of echocardiograms done at a referral hospital over five years was conducted in patients with bicuspid aortic valves with special attention to congenital abnormalities of the mitral valve. One hundred and forty patients with a bicuspid aortic valve were included. A congenital mitral valve abnormality was present in eight (5.7%, P = 0.01) with a parachute mitral valve in four (2.8%), an accessory mitral valve leaflet in one (0.7%), mitral valve prolapse in one, a cleft in one and the novel finding of a trileaflet mitral valve in one. Minor abnormalities included an elongated anterior mitral valve leaflet (P < 0.001), the increased incidence of physiological mitral regurgitation (P < 0.001), abnormal papillary muscles (P = 0.002) and an additional chord or tendon in the left ventricle cavity (P = 0.007). Mitral valve abnormalities occur more commonly in patients with bicuspid aortic valves than matched healthy individuals. The study confirms that abnormalities in these patients extend beyond the aorta. These abnormalities did not have a significant functional effect. PMID:28515127 Seth, Ashok; Rastogi, Vishal; Kumar, Vijay; Maqbool, Syed; Mustaqueem, Arif; Sekar, V. Ravi The prevalence of aortic stenosis is increasing with aging population. However with multiple co-morbidities and prior procedures in this aging population, more and more patients are being declared unfit for the ‘Gold Standard’ treatment i.e. surgical aortic valve replacement (AVR). Among the patients who are unfit or high risk for aortic valve replacement (AVR) by open heart surgery, transcatheter aortic valve implantation (TAVI) has been proven to be a valuable alternative improving survival and quality of life. We report first Indian experience of Core Valve (Medtronic Inc.) implantation in three high surgical risk patients performed on 22nd and 23rd February 2012. PMID:23993000 Aboelkassem, Yasser; Savic, Dragana; Campbell, Stuart G We have derived a mathematical model describing aortic valve dynamics and blood flow during systole. The model presents a realistic coupling between aortic valve dynamics, sinus vortex local pressure, and variations in the systemic vascular resistance. The coupling is introduced by using Hill׳s classical semi-spherical vortex model and an aortic pressure-area compliance constitutive relationship. The effects of introducing aortic sinus eddy vortices and variable systemic vascular resistance on overall valve opening-closing dynamics, left ventricular pressure, aortic pressure, blood flow rate, and aortic orifice area are examined. In addition, the strength of the sinus vortex is coupled explicitly to the valve opening angle, and implicitly to the aortic orifice area in order to predict how vortex strength varies during the four descriptive phases of aortic valve motion (fast-opening, fully-opening, slow-closing, and fast-closing). Our results compare favorably with experimental observations and the model reproduces well-known phenomena corresponding to aortic valve function such as the dicrotic notch and retrograde flow at end systole. By invoking a more complete set of physical phenomena, this new model will enable representation of pathophysiological conditions such as aortic valve stenosis or insufficiency, making it possible to predict their integrated effects on cardiac load and systemic hemodynamics. Copyright © 2014 Elsevier Ltd. All rights reserved. Yu, Zipu; Wu, Shengjun; Li, Chengchen; Zou, Yu; Ma, Liang To validate ascending aorta-lower abdominal aorta bypass grafting treatment for patients with descending aortic coarctation and an aortic valve disease. The three patients in whom a descending atypical aortic coarctation was associated with an aortic valve disease were treated with one stage surgical treatment with aortic bypass grafting through the diaphragm and aortic valve replacement in our heart center. Operative technique consisted of performing ascending aorta-lower abdominal aorta bypass grafting through diaphragm muscle and implementing aortic valve replacement. The mean time for extracorporeal circulation and occluding clamp of aorta was recorded. Blood pressure data for pre- and post-operation was measured in the limbs. Computer-enhanced transvenous angiograms of pre- and post-operation were applied for detection of aortic stenosis. The other adverse events were noticed in outpatient service during a follow-up period. The mean extracorporeal circulation time was 54 ± 11 min. The mean time for occluding clamp of aorta was 34 ± 6 min. An arterial pressure gradient was totally corrected after surgical treatment. Post-operation computer-enhanced transvenous angiograms showed the grafts to be open with a fluent flow. The patients had no gastrointestinal tract complications. No adverse event was noticed during a follow-up period in outpatient service. Treatment of ascending aorta-lower abdominal aorta bypass is advisable for patients with descending aortic coarctation and an aortic valve disease. Naci, Huseyin; Pender, Sarah; Kuehne, Titus; Kelm, Marcus Aortic valve repair is still emerging, and its role in the treatment of bicuspid aortic valve disease (BAVD) is not yet fully understood. Our objective is to synthesise available evidence on outcomes after surgical aortic valve repair in patients with BAVD. We conducted a systematic review of clinical studies using prespecified methods for searching, identifying and selecting eligible studies in 4 databases, and synthesising results (PROSPERO 2014:CRD42014014415). 2 researchers independently reviewed full-text articles and extracted data. The results of included studies were quantitatively synthesised in frequentist meta-analyses. We included 11 aortic valve repair studies or study arms with a total of 2010 participants. Pooled estimates for the proportion of patients surviving at 30 days, 1 year, 5 years and 10 years were 0.995 (95% CI 0.991 to 0.995), 0.994 (0.989 to 0.999), 0.945 (0.898 to 0.993) and 0.912 (0.845 to 0.979), respectively. The pooled proportion of late deaths from valve-related causes was 0.008 (0.000 to 0.019) at a mean follow-up of 3.5 years. Proportion of patients with valve-related reinterventions was 0.075 (0.037 to 0.113) at a mean follow-up of 3.9 years, and the linearised reintervention rate was 1.3 (0.7 to 1.9) per 100 patient-years. Outcome reporting was insufficient to pool the results for a number of predefined outcomes. In conclusion, existing evidence on aortic valve repair in BAVD is limited to mostly small case series, case–control and small retrospective cohort studies. Despite the low quality, available evidence suggests favourable survival outcomes after aortic valve repair in selected patients with BAVD. Valve-related reinterventions at follow-up are common in all patients undergoing repair surgery. PMID:28008357 Mathew, Verghese; Greason, Kevin L; Suri, Rakesh M; Leon, Martin B; Nkomo, Vuyisile T; Mack, Michael J; Rihal, Charanjit S; Holmes, David R Surgical aortic valve replacement had been the only definitive treatment of severe aortic stenosis before the availability of transcatheter valve technology. Historically, many patients with severe aortic stenosis had not been offered surgery, largely related to professional and patient perception regarding the risks of operation relative to anticipated benefits. Such patients have been labeled as "high risk" or "inoperable" with respect to their suitability for surgery. The availability of transcatheter aortic valve replacement affords a new treatment option for patients previously not felt to be optimal candidates for surgical valve replacement and allows for the opportunity to reexamine the methods for assessing operative risk in the context of more than 1 available treatment. Standardized risk assessment can be challenging because of both the imprecision of current risk scoring methods and the variability in ascertaining risk related to operator experience as well as local factors and practice patterns at treating facilities. Operative risk in actuality is not an absolute but represents a spectrum from very low to extreme, and the conventional labels of high risk and inoperable are incomplete with respect to their utility in clinical decision making. Moving forward, the emphasis should be on developing an individual assessment that takes into account procedure risk as well as long-term outcomes evaluated in a multidisciplinary fashion, and incorporating patient preferences and goals in a model of shared decision making. Jones, Brandon M; Tuzcu, E Murat; Krishnaswamy, Amar; Popovic, Zoran; Mick, Stephanie; Roselli, Eric E; Gul, Sajjad; Devgun, Jasneet; Mistry, Sohi; Jaber, Wael A; Svensson, Lars G; Kapadia, Samir R Moderate to severe aortic regurgitation after transcatheter aortic valve replacement is associated with worse outcomes. The impact of mild aortic regurgitation has been less clear, possibly because of the broad categories that have been used in clinical trials, but holds increasing importance in the study of next-generation devices in low- and intermediate-risk cohorts. A more granular scheme, which is common in clinical practice and proposed for future trials, may add prognostic value. We evaluated all patients undergoing transfemoral transcatheter aortic valve replacement at the Cleveland Clinic from 2006 to 2012. The degree of aortic regurgitation after transcatheter aortic valve replacement was reported from the echocardiography database based on a clinical, transthoracic echocardiogram performed within 30 days of the procedure. Aortic regurgitation was finely discriminated on the basis of a multiwindow, multiparametric, integrative approach using our usual clinical scale: none, trivial to 1+, 1+, 1 to 2+, 2+, 2 to 3+, 3+, 3 to 4+, or 4+. There were 237 patients included in the analysis. By controlling for age, gender, Society of Thoracic Surgeons score, baseline ejection fraction, and aortic regurgitation before transcatheter aortic valve replacement, there was a significant increase in mortality for each half grade of aortic regurgitation compared with the complete absence of aortic regurgitation after transcatheter aortic valve replacement. The unit hazard ratio for each 1+ increase in aortic regurgitation after transcatheter aortic valve replacement was 2.26 (95% confidence interval, 1.48-3.43; P < .001) considering aortic regurgitation as a continuous variable. Other clinical variables did not significantly affect mortality. Even mild aortic regurgitation after transcatheter aortic valve replacement is associated with worse long-term mortality. There may be prognostic value in reporting milder categories of aortic regurgitation with more granular Hata, T; Fujiwara, K; Furukawa, H; Tsushima, Y; Yoshitaka, H; Kuinose, M; Minami, H; Ishida, A; Tamura, K; Totsugawa, T; Kanemitsu, H; Ozawa, M Recent reports have shown that aortic valve replacement in elderly patients over 65 years with atherosclerotic aortic stenosis and a small aortic annulus is possible by using a small sized bioprosthesis (Carpentier-Edwards pericardial valve). Here we present out surgical technique. Firstly, the native calcified aortic valve was removed completely to gain total exposure of the surrounding aortic root and sinus of Valsalva like Bentall procedure. Secondly, a small sized bioprosthesis was implanted with intermittent noneverting mattress 2-0 sutures with spaghetti and small polytetrafluoroethylene (PTFE) felt. Aortic annulus is the dilated by inserting Hegar dilator sizing from 25 to 27 mm. Therefore, aortic valve replacement for small aortic annulus in intra- or supra-annular position should be easily accomplished. Good surgical results and hemodynamic state were achieved in 25 consecutive cases using this technique. Wirrig, Elaine E.; Yutzey, Katherine E. There is increasing evidence for activation of developmental transcriptional regulatory pathways in heart valve disease. Here we review molecular regulatory mechanisms involved in heart valve progenitor development, leaflet morphogenesis, and extracellular matrix organization that also are active in diseased aortic valves. These include regulators of endothelial-to-mesenchymal transitions, such as the Notch pathway effector RBPJ, and the valve progenitor markers Twist1, Msx1/2, and Sox9. Little is known of the potential reparative or pathological functions of these developmental mechanisms in adult aortic valves, but it is tempting to speculate that valve progenitor cells could contribute to repair in the context of disease. Likewise, loss of either RBPJ or Sox9 leads to aortic valve calcification in mice, supporting a potential therapeutic role in prevention of disease. During aortic valve calcification, transcriptional regulators of osteogenic development are activated in addition to valve progenitor regulatory programs. Specifically, the transcription factor Runx2 and its downstream target genes are induced in calcified valves. Runx2 and osteogenic genes also are induced with vascular calcification, but activation of valve progenitor markers and the cellular context of expression are likely to be different for valve and vascular calcification. Additional research is necessary to determine if developmental mechanisms contribute to valve repair or if these pathways can be harnessed for new treatments of heart valve disease. PMID:24665126 Jain, Rakesh; Kader, Muneer; Sajeev, C.G.; Krishnan, M.N. Bicuspid aortic valve is the most common congenital cardiac malformation, affecting 1%–2% of the population. Among various complications, incidence of infective endocarditis (IE) in the bicuspid aortic valve population is high with higher rate of periannular extension resulting in conduction disturbances. Here we are reporting a rare case of infective endocarditis of bicuspid aortic valve presented with alternating bundle branch block. PMID:26138186 Evangelista, Arturo; Gallego, Pastora; Calvo-Iglesias, Francisco; Bermejo, Javier; Robledo-Carmona, Juan; Sánchez, Violeta; Saura, Daniel; Arnold, Roman; Carro, Amelia; Maldonado, Giuliana; Sao-Avilés, Augusto; Teixidó, Gisela; Galian, Laura; Rodríguez-Palomares, José; García-Dorado, David Bicuspid aortic valve (BAV) is associated with early valvular dysfunction and proximal aorta dilation with high heterogeneity. This study aimed to assess the determinants of these complications. Eight hundred and fifty-two consecutive adults diagnosed of BAV referred from cardiac outpatient clinics to eight echocardiographic laboratories of tertiary hospitals were prospectively recruited. Exclusion criteria were aortic coarctation, other congenital disorders or intervention. BAV morphotype, significant valve dysfunction and aorta dilation (≥2 Z-score) at sinuses and ascending aorta were established. Three BAV morphotypes were identified: right-left coronary cusp fusion (RL) in 72.9%, right-non-coronary (RN) in 24.1% and left-non-coronary (LN) in 3.0%. BAV without raphe was observed in 18.3%. Multivariate analysis showed aortic regurgitation (23%) to be related to male sex (OR: 2.80, p<0.0001) and valve prolapse (OR: 5.16, p<0.0001), and aortic stenosis (22%) to BAV-RN (OR: 2.09, p<0.001), the presence of raphe (OR: 2.75, p<0.001), age (OR: 1.03; p<0.001), dyslipidaemia (OR: 1.77, p<0.01) and smoking (OR: 1.63, p<0.05). Ascending aorta was dilated in 76% without differences among morphotypes and associated with significant valvular dysfunction. By contrast, aortic root was dilated in 34% and related to male sex and aortic regurgitation but was less frequent in aortic stenosis and BAV-RN. Normofunctional valves are more prevalent in BAV without raphe. Aortic stenosis is more frequent in BAV-RN and associated with some cardiovascular risk factors, whereas aortic regurgitation (AR) is associated with male sex and sigmoid prolapse. Although ascending aorta is the most commonly dilated segment, aortic root dilation is present in one-third of patients and associated with AR. Remarkably, BAV-RL increases the risk for dilation of the proximal aorta, whereas BAV-RN spares this area. © Article author(s) (or their employer(s) unless otherwise stated in the text of the Rashid, Hashrul N Z; Gooley, Robert; McCormick, Liam; Zaman, Sarah; Ramkumar, Satish; Jackson, Damon; Amiruddin, Ameera; Nasis, Arthur; Cameron, James; Meredith, Ian T To determine the safety and efficacy of valve repositioning following transcatheter aortic valve replacement (TAVR) with the Lotus Valve System (Boston Scientific, Marlborough, MA, USA). TAVR is a well-established treatment for severe aortic stenosis. The Lotus Valve System is fully repositionable and retrievable. Valve repositioning has the potential to minimize TAVR-related complications caused by valve malposition; however, the effect on adverse event rates such as stroke is unknown. Consecutive patients with severe aortic stenosis treated with the Lotus Valve System (n=125) were prospectively recruited. Patients who did not require valve repositioning (Group A) were compared to patients who required one or more valve repositions (Group B). The primary end-point was 30-day occurrence of major adverse cardiovascular and cerebrovascular events (MACCE). Secondary end-points included each component of the primary end-point, new pacemaker insertion, and procedural or 30-day major adverse events, defined according to VARC-2 definitions. Valve repositioning was utilized in 60.8% (76/125) of patients including 17.1% (13/76) who required full valve resheathing. The most frequent indications for valve repositioning were altering the depth and angulation of initial implantation (69.7%), reducing paravalvular regurgitation (13.2%), and attempt to correct new or worsened heart block (7.9%). Baseline characteristics were similar in both groups. The primary end-point occurred in 12.2% and 6.6% of Group A and B, respectively (p=0.10). Thirty-day new pacemaker implantation was 34.1% and 18.8% in Group A and B, respectively (p=0.06). The secondary end-point measures were not significantly different between the groups. Repositioning facilitated correct anatomical positioning of all devices leading to optimal prosthesis hemodynamics and a trend to lower pacemaker rate without increased risk of MACCE. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All Shehatha, Jaffar S; Taha, Abdulsalam Y A 66-year-old Australian man underwent elective replacement of a severely stenotic aortic valve with a 22-mm Medtronic-Hall valve. Six weeks later, he was readmitted with worsening dyspnea, fever, and mild anemia. Investigations confirmed pulmonary edema and moderate periprosthetic aortic regurgitation. The pulmonary edema was managed conservatively, and a second 22-mm Medtronic-Hall valve was implanted. Infective endocarditis was suspected in the aortic annulus below the orifice of the right coronary artery. A bacteriological study revealed a rare bacteria of Streptomyces species. The patient received intensive antibiotic therapy over a 6-week period of hospitalization, and the aortic regurgitation disappeared one week postoperatively. Kwon, Hee-Jin; Kim, Song Soo; Sun, Byung Joo; Jin, Sun Ah; Kim, Jun-Hyung; Lee, Jae-Hwan; Choi, Siwan; Jeong, Jin-Ok; Seong, In-Whan Unicuspid aortic valve (UAV) is an extremely rare form of congenital aortic valvular abnormality. Although UAV shows similar clinical characteristics to bicuspid aortic valve, the clinical symptoms develop at earlier age and progress at a faster pace in UAV. In this report, we are presenting a 42-year-old male with severe aortic stenosis associated with unicommissural UAV. The patients underwent a successful Bentall operation. PMID:27721957 Minami, Keisuke; Yoneyama, Kihei; Izumo, Masaki; Suzuki, Kengo; Ogawa, Yasuyoshi; Chikaraishi, Kousuke; Ogawa, Yukihisa; Kobayashi, Yasuyuki; Furukawa, Toshiyuki; Tanabe, Yasuhiro; Akashi, Yoshihiro J Computed tomography is the best noninvasive imaging modality for evaluating valve leaflet calcification. To evaluate the association of aortic valve leaflet calcification with instantaneous valve opening and closing using dynamic multidetector computed tomography (MDCT). We retrospectively evaluated 58 consecutive patients who underwent dynamic MDCT imaging. Aortic valve calcification (AVC) was quantified using the Agatston method. The aortic valve area (AVA) tracking curves were derived by planimetry during the cardiac cycle using all 20 phases (5% reconstruction). da/dt in cm(2)/s was calculated as the rate of change of AVA during opening (positive) or closing (negative). Patients were divided into 3 three groups according to Agatston score quartile: no AVC (Q2, Score 0, n = 18), mild AVC (Q3, Score 1-2254, n = 24), and severe AVC (Q4 Score >2254, n = 14). In multivariable linear regression, compared to the non AVC group, the mild and severe AVC groups had lower maximum AVA (by -1.71 cm(2) and -2.25 cm(2), respectively), lower peak positive da/dt (by -21.88 cm(2)/s and -26.65 cm(2)/s, respectively), and higher peak negative da/dt (by 13.78 cm(2)/s and 18.11 cm(2)/s, respectively) (p < 0.05 for all comparisons). AVA and its opening and closing were influenced by leaflet calcification. The present study demonstrates the ability of dynamic MDCT imaging to assess quantitative aortic valve motion in a clinical setting. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved. Gatti, Giuseppe; Benussi, Bernardo; Camerini, Fulvio; Pappalardo, Aniello Four patients referred for surgical treatment of aortic stenosis presented an unexpected extremely calcified (porcelain) ascending aorta at the intraoperative epiaortic ultrasonography scanning. In each patient, replacement of the aortic valve was successfully performed using a sutureless implantable bioprosthesis during a short period of hypothermic circulatory arrest. In the era of transcatheter aortic valve implantation procedures, the sutureless valve may be a valuable option for surgical units that do not dispose of transcatheter technology or a hybrid operative theatre. ... Rekha Mankad, M.D. References AskMayoExpert. Valvular disease – aortic stenosis. Rochester, Minn.: Mayo Foundation for Medical Education and ... Original article: http://www.mayoclinic.org/diseases-conditions/aortic-stenosis/expert-answers/aortic-valve-calcification/FAQ-20058525 . Mayo ... Singh, Vikas; Macon, Conrad J; Scot Shaw, Eric; Londoño, Juan C; Martinez, Claudia A Transcatheter aortic valve replacement has emerged as an alternative option for inoperable or very high-risk patients with severe aortic stenosis-however, there are serious complications associated with the procedure, such as patient mortality, stroke, conduction disturbances, paravalvular regurgitation, and vascular concerns. Our review focuses on the most common complications related to transcatheter aortic valve replacement procedures and potential bailout strategies and techniques. Bernabeu, Eduardo; Mestres, Carlos A; Loma-Osorio, Pablo; Josa, Miguel Traumatic rupture of intracardiac structures is an uncommon phenomenon although there are a number of reports with regards to rupture of the tricuspid, mitral and aortic valves. We report the case of a 25-year-old patient who presented with acute aortic and mitral valve regurgitation of traumatic origin. Both lesions were seen separated by 2 weeks. Pathophysiology is reviewed. The combination of both aortic and mitral lesions following blunt chest trauma is almost exceptional. Zajarias, Alan; Cribier, Alain G The concept of transcatheter aortic valve replacement was developed with the goal of offering a therapeutic solution to patients with severe symptomatic aortic stenosis who are not considered good candidates for surgical valve replacement. Initial attempts were complicated by vascular access problems and lack of appropriate tools. With time and experience, early problems were solved and the concepts of valve sizing, valve positioning, and patient selection were defined. Technological improvements allowed the use of smaller arterial sheaths to decrease vascular trauma, special catheters to facilitate valve delivery, and treatments on the valve prostheses that would ensure longer durability. After 5 years, the number of transcatheter aortic valve replacements has grown significantly, and will likely continue as this technology becomes increasingly available. Currently, 2 valve models, the Edwards SAPIEN valve (Edwards Lifescience, Irvine, California) and the CoreValve ReValving system (CoreValve Inc., Irvine, California), have been used in over 4,000 cases worldwide for the treatment of symptomatic aortic stenosis. Midterm follow-up shows no evidence of restenosis or prosthetic valve dysfunction. Transfemoral and transapical delivery routes can be selected depending on the quality of vascular access and the type of prosthesis used. Randomized trials that are currently underway will confirm procedural safety and guide the applicability of this technology. Szymański, Piotr; Hryniewiecki, Tomasz; Dąbrowski, Maciej; Sorysz, Danuta; Kochman, Janusz; Jastrzębski, Jan; Kukulski, Tomasz; Zembala, Marian Objective To analyse the impact of postprocedural mitral regurgitation (MR), in an interaction with aortic regurgitation (AR), on mortality following transcatheter aortic valve implantation (TAVI). Methods To assess the interaction between MR and AR, we compared the survival rate of patients (i) without both significant MR and AR versus (ii) those with either significant MR or significant AR versus (iii) with significant MR and AR, all postprocedure. 381 participants of the Polish Transcatheter Aortic Valve Implantation Registry (166 males (43.6%) and 215 females (56.4%), age 78.8±7.4 years) were analysed. Follow-up was 94.1±96.5 days. Results Inhospital and midterm mortality were 6.6% and 10.2%, respectively. Significant MR and AR were present in 16% and 8.1% patients, including 3.1% patients with both significant MR and AR. Patients with significant versus insignificant AR differed with respect to mortality (log rank p=0.009). This difference was not apparent in a subgroup of patients without significant MR (log rank p=0.80). In a subgroup of patients without significant AR, there were no significant differences in mortality between individuals with versus without significant MR (log rank p=0.44). Significant MR and AR had a significant impact on mortality only when associated with each other (log rank p<0.0001). At multivariate Cox regression modelling concomitant significant MR and AR were independently associated with mortality (OR 3.2, 95% CI 1.54 to 5.71, p=0.002). Conclusions Significant MR or AR postprocedure, when isolated, had no impact on survival. Combined MR and AR had a significant impact on a patient's prognosis. PMID:26908096 Bruschi, Giuseppe; De Marco, Federico; Oreglia, Jacopo; Colombo, Paola; Fratto, Pasquale; Lullo, Francesca; Paino, Roberto; Frigerio, Maria; Martinelli, Luigi; Klugmann, Silvio Concerns exist in the field of transcatheter aortic valve implantation regarding the treatment of patients with mechanical mitral valve for possible interference between the percutaneous aortic valve and the mechanical mitral prosthesis. We report our experience with percutaneous aortic valve implantation in 4 patients with severe aortic stenosis, previously operated on for mitral valve replacement with a mechanical prosthesis. All patients underwent uneventful percutaneous retrograde CoreValve implantation (CoreValve Inc, Irvine, CA). No deformation of the nitinol tubing of the prostheses (ie, neither distortion nor malfunction of the mechanical valve in the mitral position) occurred in any of the patients. All patients are alive and asymptomatic at a mean follow-up of 171 days. Ostrovsky, Yury; Spirydonau, Siarhei; Shchatsinka, Mikalai; Shket, Aliaksandr Surgical treatment of infective and prosthetic endocarditis using allografts gives good results. Aortic allograft implantation is a common technique, while tricuspid valve replacement with a mitral allograft is very rare. Multiple valve disease in case of infective endocarditis is a surgical challenge as such patients are usually in a grave condition and results of surgical treatment are often unsatisfactory. In this article we describe a clinical case of successful surgical treatment in a patient with active infective endocarditis of aortic and tricuspid valve, complicated by an aortic-right ventricular fistula. The aortic valve and ascending aorta were replaced with a cryopreserved aortic allograft; the tricuspid valve was replaced with a cryopreserved mitral allograft. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. Ribeiro, Henrique Barbosa; Sarmento-Leite, Rogério; Siqueira, Dimytri A. A.; Carvalho, Luiz Antônio; Mangione, José Armando; Rodés-Cabau, Josep; Perin, Marco A.; de Brito, Fábio Sandoli Background Transcatheter aortic valve implantation (TAVI) was established as an important alternative for high-risk patients with severe aortic stenosis. However, there are few data in the literature regarding coronary obstruction, that although rare, is a potentially fatal complication. Objective Evaluate this complication in Brazil. Methods We evaluated all patients presenting coronary obstruction from the Brazilian Registry of TAVI. Main baseline and procedural characteristics, management of the complication, and clinical outcomes were collected from all patients. Results From 418 consecutive TAVI procedures, coronary obstruction occurred in 3 cases (incidence of 0.72%). All patients were women, without prior coronary artery bypass grafting (CABG), and with mean age of 85 ± 3 years, logistic EuroSCORE of 15 ± 6% and STS-PROM score of 9 ± 4%. All of the cases were performed with balloon-expandable Sapien XT prosthesis. In one patient, with pre-procedural computed tomography data, coronary arteries presented a low height and a narrow sinus of Valsalva. All patients presented with clinically significant severe maintained hypotension, immediately after valve implantation, and even though coronary angioplasty with stent implantation was successfully performed in all cases, patients died during hospitalization, being two periprocedurally. Conclusion Coronary obstruction following TAVI is a rare but potentially fatal complication, being more frequent in women and with the balloon-expandable prosthesis. Anatomical factors might be related with its increased occurrence, highlighting the importance of a good pre-procedural evaluation of the patients in order to avoid this severe complication. PMID:24652089 Ribeiro, Henrique Barbosa; Sarmento-Leite, Rogério; Siqueira, Dimytri A A; Carvalho, Luiz Antônio; Mangione, José Armando; Rodés-Cabau, Josep; Perin, Marco A; Brito, Fábio Sandoli de Transcatheter aortic valve implantation (TAVI) was established as an important alternative for high-risk patients with severe aortic stenosis. However, there are few data in the literature regarding coronary obstruction, that although rare, is a potentially fatal complication. Evaluate this complication in Brazil. We evaluated all patients presenting coronary obstruction from the Brazilian Registry of TAVI. Main baseline and procedural characteristics, management of the complication, and clinical outcomes were collected from all patients. From 418 consecutive TAVI procedures, coronary obstruction occurred in 3 cases (incidence of 0.72%). All patients were women, without prior coronary artery bypass grafting (CABG), and with mean age of 85 ± 3 years, logistic EuroSCORE of 15 ± 6% and STS-PROM score of 9 ± 4%. All of the cases were performed with balloon-expandable Sapien XT prosthesis. In one patient, with pre-procedural computed tomography data, coronary arteries presented a low height and a narrow sinus of Valsalva. All patients presented with clinically significant severe maintained hypotension, immediately after valve implantation, and even though coronary angioplasty with stent implantation was successfully performed in all cases, patients died during hospitalization, being two periprocedurally. Coronary obstruction following TAVI is a rare but potentially fatal complication, being more frequent in women and with the balloon-expandable prosthesis. Anatomical factors might be related with its increased occurrence, highlighting the importance of a good pre-procedural evaluation of the patients in order to avoid this severe complication. Tomsic, Anton; Li, Wilson W L; van Paridon, Marieke; Bindraban, Navin R; de Mol, Bas A J M Mitral valve leaflet aneurysm is a rare and potentially devastating complication of aortic valve endocarditis. We report the case of a 48-year-old man who had endocarditis of the native aortic valve and a concomitant aneurysm of the anterior mitral valve leaflet. Severe mitral regurgitation occurred after the aneurysm perforated. The patient showed no signs of heart failure and completed a 6-week regimen of antibiotic therapy before undergoing successful aortic and mitral valve replacement. In addition to the patient's case, we review the relevant medical literature. Shrestha, Malakh; Maeding, Ilona; Höffler, Klaus; Koigeldiyev, Nurbol; Marsch, Georg; Siemeni, Thierry; Fleissner, Felix; Haverich, Axel OBJECTIVES Aortic valve replacement (AVR) in geriatric patients (>75 years) with small aortic roots is a challenge. Patient–prosthesis mismatch and the long cross-clamp time necessary for stentless valves or root enlargement are matters of concern. We compared the results of AVR with sutureless valves (Sorin Perceval), against those with conventional biological valves. METHODS Between April 2007 and December 2012, 120 isolated AVRs were performed in patients with a small annulus (<22 mm) at our centre. In 70 patients (68 females, age 77.4 ± 5.5 years), conventional valves (C group) and in 50 patients (47 females, age 79.8 ± 4.5 years), sutureless valves (P group) were implanted. The Logistic EuroSCORE of the C group was 16.7 ± 10.4 and that of the P group 20.4 ± 10.7, (P = 0.054). Minimal-access surgery was performed in 4.3% (3/70) patients in the C group and 72% (36/50) patients in the P group. RESULTS The cardiopulmonary bypass (CPB) and cross-clamp times of the C group were 75.3 ± 23 and 50.3 ± 14.2 min vs 58.7 ± 20.9 and 30.1 ± 9 min in the P group, (P < 0.001). In the C group, two annulus enlargements were performed. Thirty-day mortality was 4.3% (n = 3) in the C group and 0 in the P group, (n.s.). At follow-up (up to 5 years), mortalities were 17.4% (n = 12) in the C group and 14% (n = 7) in the P group, (n.s.). CONCLUSIONS This study highlights the advantages of sutureless valves for geriatric patients with small aortic roots reflected by shorter cross-clamp and CPB times, even though most of these patients were operated on via a minimally invasive access. Moreover, due to the absence of a sewing ring, these valves are also almost stentless, with greater effective orifice area (EOA) for any given size. This may potentially result in better haemodynamics even without the root enlargement. This is of advantage, as several studies have shown that aortic root enlargement can significantly increase the risks of AVR. Moreover, as seen in this series Shrestha, Malakh; Maeding, Ilona; Höffler, Klaus; Koigeldiyev, Nurbol; Marsch, Georg; Siemeni, Thierry; Fleissner, Felix; Haverich, Axel Aortic valve replacement (AVR) in geriatric patients (>75 years) with small aortic roots is a challenge. Patient-prosthesis mismatch and the long cross-clamp time necessary for stentless valves or root enlargement are matters of concern. We compared the results of AVR with sutureless valves (Sorin Perceval), against those with conventional biological valves. Between April 2007 and December 2012, 120 isolated AVRs were performed in patients with a small annulus (<22 mm) at our centre. In 70 patients (68 females, age 77.4 ± 5.5 years), conventional valves (C group) and in 50 patients (47 females, age 79.8 ± 4.5 years), sutureless valves (P group) were implanted. The Logistic EuroSCORE of the C group was 16.7 ± 10.4 and that of the P group 20.4 ± 10.7, (P = 0.054). Minimal-access surgery was performed in 4.3% (3/70) patients in the C group and 72% (36/50) patients in the P group. The cardiopulmonary bypass (CPB) and cross-clamp times of the C group were 75.3 ± 23 and 50.3 ± 14.2 min vs 58.7 ± 20.9 and 30.1 ± 9 min in the P group, (P < 0.001). In the C group, two annulus enlargements were performed. Thirty-day mortality was 4.3% (n = 3) in the C group and 0 in the P group, (n.s.). At follow-up (up to 5 years), mortalities were 17.4% (n = 12) in the C group and 14% (n = 7) in the P group, (n.s.). This study highlights the advantages of sutureless valves for geriatric patients with small aortic roots reflected by shorter cross-clamp and CPB times, even though most of these patients were operated on via a minimally invasive access. Moreover, due to the absence of a sewing ring, these valves are also almost stentless, with greater effective orifice area (EOA) for any given size. This may potentially result in better haemodynamics even without the root enlargement. This is of advantage, as several studies have shown that aortic root enlargement can significantly increase the risks of AVR. Moreover, as seen in this series, these valves may also enable a broader Mathieu, Patrick; Bouchareb, Rihab Calcific aortic valve disease (CAVD) is the most common heart valve disorder. CAVD is a chronic process characterized by a pathologic mineralization of valve leaflets. Ectopic mineralization of the aortic valve involves complex relationships with immunity. Studies have highlighted that both innate and adaptive immunity play a role in the development of CAVD. In this regard, accumulating evidence indicates that fibrocalcific remodelling of the aortic valve is associated with activation of the NF-κB pathway. The expression of TNF-α and IL-6 is increased in human mineralized aortic valves and promotes an osteogenic program as well as the mineralization of valve interstitial cells (VICs), the main cellular component of the aortic valve. Different factors, including oxidized lipid species, activate the innate immune response through the Toll-like receptors. Moreover, VICs express 5-lipoxygenase and therefore produce leukotrienes, which may amplify the inflammatory response in the aortic valve. More recently, studies have emphasized that an adaptive immune response is triggered during CAVD. Herein, we are reviewing the link between the immune response and the development of CAVD and we have tried, whenever possible, to keep a translational approach. PMID:26065007 Mathieu, Patrick; Bouchareb, Rihab; Boulanger, Marie-Chloé Calcific aortic valve disease (CAVD) is the most common heart valve disorder. CAVD is a chronic process characterized by a pathologic mineralization of valve leaflets. Ectopic mineralization of the aortic valve involves complex relationships with immunity. Studies have highlighted that both innate and adaptive immunity play a role in the development of CAVD. In this regard, accumulating evidence indicates that fibrocalcific remodelling of the aortic valve is associated with activation of the NF-κB pathway. The expression of TNF-α and IL-6 is increased in human mineralized aortic valves and promotes an osteogenic program as well as the mineralization of valve interstitial cells (VICs), the main cellular component of the aortic valve. Different factors, including oxidized lipid species, activate the innate immune response through the Toll-like receptors. Moreover, VICs express 5-lipoxygenase and therefore produce leukotrienes, which may amplify the inflammatory response in the aortic valve. More recently, studies have emphasized that an adaptive immune response is triggered during CAVD. Herein, we are reviewing the link between the immune response and the development of CAVD and we have tried, whenever possible, to keep a translational approach. Mossad, S B; Tomford, J W; Stewart, R; Ratliff, N B; Hall, G S We describe the first case of prosthetic valve endocarditis due to a Streptomyces sp. The patient presented with fever, cutaneous embolic lesions, and bacteremia 3 months after aortic valve replacement. Treatment required valve replacement and a long course of parenteral imipenem. PMID:8586732 Krishnamurthy, Varun K.; Guilak, Farshid; Narmoneva, Daria A.; Hinton, Robert B. Site-specific biomechanical properties of the aortic valve play an important role in native valve function, and alterations in these properties may reflect mechanisms of degeneration and disease. Small animals such as targeted mutagenesis mice provide a powerful approach to model human valve disease pathogenesis; however, physical mechanical testing in small animals is limited by valve tissue size. Aortic valves are comprised of highly organized extracellular matrix compartmentalized in cusp and annulus regions, which have different functions. The objective of this study was to measure regional mechanical properties of mouse aortic valve tissue using a modified micropipette aspiration technique. Aortic valves were isolated from juvenile, adult and aged adult C57BL/6 wild type mice. Tissue tensile stiffness was determined for annulus and cusp regions using a half-space punch model. Stiffness for the annulus region was significantly higher compared to the cusp region at all stages. Further, aged adult valve tissue had decreased stiffness in both the cusp and annulus. Quantitative histochemical analysis revealed a collagen-rich annulus and a proteoglycan-rich cusp at all stages. In aged adult valves, there was proteoglycan infiltration of the annulus hinge, consistent with observed mechanical differences over time. These findings indicate that valve tissue biomechanical properties vary in wild type mice in a region-specific and age-related manner. The micropipette aspiration technique provides a promising approach for studies of valve structure and function in small animal models, such as transgenic mouse models of valve disease. PMID:20863504 Keshavarz-Motamed, Zahra; Maftoon, Nima Aortic valve stenosis, which causes considerable constriction of the flow passage, is one of the most frequent cardiovascular diseases and is the most common cause of the valvular replacements which take place for around 100,000 per year in North America. Furthermore, it is considered as the most frequent cardiac disease after arterial hypertension and coronary artery disease. The objective of this study is to develop an analytical model considering the coupling effect between fluid flow and elastic deformation with reasonable boundary conditions to describe the effect of AS on the left ventricle and the aorta. The pulsatile and Newtonian blood flow through aortic stenosis with vascular wall deformability is analyzed and its effects are discussed in terms of flow parameters such as velocity, resistance to flow, shear stress distribution and pressure loss. Meanwhile we developed analytical expressions to improve the comprehension of the transvalvular hemodynamics and the aortic stenosis hemodynamics which is of great interest because of one main reason. To medical scientists, an accurate knowledge of the mechanical properties of whole blood flow in the aorta can suggest a new diagnostic tool. Niemelä, K; Ikäheimo, M; Takkunen, J Preoperative and sequential postoperative bicycle exercise tests were compared with clinical and catheterization data in assessment of the functional outcome of uncomplicated aortic valve replacement (AVR) in 33 patients. The operation was done because of aortic stenosis (AS) in 14 patients and aortic regurgitation (AR) in 19. Both groups of patients showed improved NYHA functional class and peak achieved workload after AVR, but the results in these respects did not correlate. Nor did the regression in left ventricular (LV) hypertrophy and dilatation after AVR that was seen in both patient groups correlate with the changes measured in exercise tolerance. Preoperative exercise capacity was not predictive of the postoperative performance. In the AR patients, however, preoperative ability to raise the systolic blood pressure during exercise appeared to predict which patients were likely to show enhanced resting LV systolic pump function after AVR. It is concluded that objective tests of exercise tolerance alone permit reliable evaluation of the functional outcome of uncomplicated AVR. Indices of resting LV performance, though helpful in observation of the changes resulting from removal of the untoward LV burden after AVR, are likely to be less useful for evaluating changes in the LV exercise reserve. The response of the systolic blood pressure to exercise may be an additional predictive factor for postoperative resting LV performance in patients with AR. Maluenda, Gabriel; Araya, Mario; Ibañez-Arenas, Rodrigo Although transcatheter aortic valve replacement (TAVR) has been accepted as an attractive alternative for high-risk patients with severe symptomatic aortic stenosis (AS), patients with congenital bicuspid AS has been typically disqualified for this indication due to an implied risk of device dislocation, distortion, or device malfunctioning. Nonetheless, bicuspid AS is not uncommon and frequently missed by transthoracic echocardiography. We reported an interesting case of a high-risk patient with severe symptomatic bicuspid AS who underwent successful TAVR and discussed the anatomic requirements for a safe implant in patients with bicuspid AS considered candidates for TAVR. Copyright © 2013 Wiley Periodicals, Inc. Urban, Marian; Pirk, Jan; Szarszoi, Ondrej; Skalsky, Ivo; Maly, Jiri; Netuka, Ivan BACKGROUND: Double valve replacement for concomitant aortic and mitral valve disease is associated with substantial morbidity and mortality. Excellent results with valve repair in isolated mitral valve lesions have been reported; therefore, whether its potential benefits would translate into better outcomes in patients with combined mitral-aortic disease was investigated. METHODS: A retrospective observational study was performed involving 341 patients who underwent aortic valve replacement with either mitral valve repair (n=42) or double valve replacement (n=299). Data were analyzed for early mortality, late valve-related complications and survival. RESULTS: The early mortality rate was 11.9% for valve repair and 11.0% for replacement (P=0.797). Survival (± SD) was 67±11% in mitral valve repair with aortic valve replacement and 81±3% in double valve replacement at five years of follow-up (P=0.187). The percentage of patients who did not experience major adverse valve-related events at five years of follow-up was 83±9% in those who underwent mitral valve repair with aortic valve replacement and 89±2% in patients who underwent double valve replacement (P=0.412). Age >70 years (HR 2.4 [95% CI 1.1 to 4.9]; P=0.023) and renal dysfunction (HR 1.9 [95% CI 1.2 to 3.7]; P=0.01) were independent predictors of decreased survival. CONCLUSIONS: In patients with double valve disease, both mitral valve repair and replacement provided comparable early outcomes. There were no significant differences in valve-related reoperations, anticoagulation-related complications or prosthetic valve endocarditis. Patient-related factors appear to be the major determinant of late survival, irrespective of the type of operation. PMID:24294032 Marshall, D A; Jackson, R; Rae, A P; Capell, H A Aortic regurgitation associated with relapsing polychondritis usually occurs late in the disease as a result of aortic root dilatation. A case where aortic regurgitation occurred early and was due to cusp rupture with a normal aortic root is reported. The patient required urgent aortic valve replacement within six weeks of developing a murmur despite apparent control of inflammation with immunosuppressive treatment. The possibility of cusp rupture with sudden haemodynamic deterioration should be considered in patients with relapsing polychondritis who develop aortic regurgitation. Images PMID:1575597 Bonow, Robert O; Leon, Martin B; Doshi, Darshan; Moat, Neil The management of aortic valve disease has been improved by accurate diagnosis and assessment of severity by echocardiography and advanced imaging techniques, efforts to elicit symptoms or objective markers of disease severity and progression, and consideration of optimum timing of aortic valve replacement, even in elderly patients. Prevalence of calcific aortic stenosis is growing in ageing populations. Conventional surgery remains the most appropriate option for most patients who require aortic valve replacement, but the transcatheter approach is established for high-risk patients or poor candidates for surgery. The rapid growth of transcatheter aortic valve replacement has been fuelled by improved technology, evidence-based clinical research, and setting up of multidisciplinary heart teams. Aortic regurgitation can be difficult to diagnose and quantify. Left ventricular dysfunction often precedes symptoms, needing active surveillance by echocardiography to determine the optimum time for aortic valve replacement. Development of transcatheter approaches for aortic regurgitation is challenging, owing to the absence of valvular calcification and distortion of aortic root anatomy in many patients. Copyright © 2016 Elsevier Ltd. All rights reserved. Muretti, Mirko; Massi, Francesco; Coradduzza, Enrico; Portoghese, Michele Familial hypercholesterolemia is an inherited disorder with incidences of approximately 1:500 and 1:1,000,000 in heterozygous and homozygous form respectively. Affected patients usually show early coronary artery disease and severe aortic root calcification, despite optimization of therapy. We report a case of a 64-year-old woman affected by heterozygous familial hypercholesterolemia which presented dyspnea and anginal symptoms due to a severely calcified aortic root causing valve stenosis and narrowed sinotubular junction. Aortic valve replacement and aortic root enlargement were performed using the Manougian procedure. Even for experiences surgeons, this surgery could prove challenging for this group of patients due to aggressive degenerative tissue calcification of the aortic root, which often presents an extremely calcified aortic valve with a small annulus associated to a narrowed sinotubular junction. Koos, Ralf; Mahnken, Andreas Horst; Dohmen, Guido; Brehmer, Kathrin; Günther, Rolf W; Autschbach, Rüdiger; Marx, Nikolaus; Hoffmann, Rainer This study sought to examine a possible relationship between the severity of aortic valve calcification (AVC), the distribution of AVC and the degree of aortic valve regurgitation (AR) after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS). 57 patients (22 men, 81 ± 5 years) with symptomatic AS and with a logistic EuroSCORE of 24 ± 12 were included. 38 patients (67%) received a third (18F)-generation CoreValve® aortic valve prosthesis, in 19 patients (33%) an Edwards SAPIEN™ prosthesis was implanted. Prior to TAVI dual-source computed tomography for assessment of AVC was performed. To determine the distribution of AVC the percentage of the calcium load of the most severely calcified cusp was calculated. After TAVI the degree of AR was determined by angiography and echocardiography. The severity of AR after TAVI was related to the severity and distribution of AVC. There was no association between the distribution of AVC and the degree of paravalvular AR after TAVI as assessed by angiography (r = -0.02, p = 0.88). Agatston AVC scores were significantly higher in patients with AR grade ≥ 3 (5055 ± 1753, n = 3) than in patients with AR grade < 3 (1723 ± 967, p = 0.03, n = 54). Agatston AVC scores > 3000 were associated with a relevant paravalvular AR and showed a trend for increased need for second manoeuvres. There was a significant correlation between the severity of AVC and the degree of AR after AVR (r = 0.50, p < 0.001). Patients with severe AVC have an increased risk for a relevant AR after TAVI as well as a trend for increased need for additional procedures. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. Attia, Rizwan Q.; Hickey, Graeme L.; Grant, Stuart W.; Bridgewater, Ben; Roxburgh, James C.; Kumar, Pankaj; Ridley, Paul; Bhabra, Moninder; Millner, Russell W. J.; Athanasiou, Thanos; Casula, Roberto; Chukwuemka, Andrew; Pillay, Thasee; Young, Christopher P. Objective Minimally invasive aortic valve replacement (MIAVR) has been demonstrated as a safe and effective option but remains underused. We aimed to evaluate outcomes of isolated MIAVR compared with conventional aortic valve replacement (CAVR). Methods Data from The National Institute for Cardiovascular Outcomes Research (NICOR) were analyzed at seven volunteer centers (2006–2012). Primary outcomes were in-hospital mortality and midterm survival. Secondary outcomes were postoperative length of stay as well as cumulative bypass and cross-clamp times. Propensity modeling with matched cohort analysis was used. Results Of 307 consecutive MIAVR patients, 151 (49%) were performed during the last 2 years of study with a continued increase in numbers. The 307 MIAVR patients were matched on a 1:1 ratio. In the matched CAVR group, there was no statistically significant difference in in-hospital mortality [MIAVR, 4/307,(1.3%); 95% confidence interval (CI), 0.4%–3.4% vs CAVR, 6/307 (2.0%); 95% CI, 0.8%–4.3%; P = 0.752]. One-year survival rates in the MIAVR and CAVR groups were 94.4% and 94.6%, respectively. There was no statistically significant difference in midterm survival (P = 0.677; hazard ratio, 0.90; 95% CI, 0.56–1.46). Median postoperative length of stay was lower in the MIAVR patients by 1 day (P = 0.009). The mean cumulative bypass time (94.8 vs 91.3 minutes; P = 0.333) and cross-clamp time (74.6 vs 68.4 minutes; P = 0.006) were longer in the MIAVR group; however, this was significant only in the cross-clamp time comparison. Conclusions Minimally invasive aortic valve replacement is a safe alternative to CAVR with respect to operative and 1-year mortality and is associated with a shorter postoperative stay. Further studies are required in high-risk (logistic EuroSCORE > 10) patients to define the role of MIAVR. PMID:26926521 Kim, Yong Han; Kim, Ji Seong; Choi, Jae-Woong; Chang, Hyoung Woo; Na, Kwon Joong; Kim, Jun Sung; Kim, Kyung-Hwan Background Although unique aortic pathology related to bicuspid aortic valve (BAV) has been previously reported, clinical implications of BAV to aortopathy risk have yet to be investigated. We looked for potential differences in matrix protein expressions in the aortic wall in BAV patients. Methods Aorta specimens were obtained from 31 patients: BAV group (n=27), tricuspid aortic valve (TAV) group (n=4). The BAV group was categorized into three subgroups: left coronary sinus-right coronary sinus (R+L group; n=13, 42%), right coronary sinus-non-coronary sinus (R+N group; n=8, 26%), and anteroposterior (AP group; n=6, 19%). We analyzed the expression of endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP)-9, and tissue inhibitor of matrix metalloproteinase (TIMP)-2. Results Based on the mean value of the control group, BAV group showed decreased expression of eNOS in 72.7% of patients, increased MMP-9 in 82.3%, and decreased TIMP in 79.2%. There was a higher tendency for aortopathy in the BAV group: eNOS (BAV:TAV)= 53%±7%:57%±11%, MMP-9 (BAV:TAV)=48%±10%:38%±1%. The AP group showed lower expression of eNOS than the fusion (R+L, R+N) group did; 48%±5% vs. 55%±7% (p=0.081). Conclusion Not all patients with BAV had expression of aortopathy; however, for patients who had a suspicious form of bicuspid valve, aortic wall biopsy could be valuable to signify the presence of aortopathy. PMID:27965921 Forrest, John K Transcatheter aortic valve replacement (TAVR) is a new technology that recently has been shown to improve survival and quality of life in patients with severe symptomatic aortic stenosis who are not surgical candidates. The development and design of transcatheter valves has been ongoing for the past 20 years, and TAVR has now been approved by the FDA as a treatment for aortic stenosis in patients who are not surgical candidates. In the United States, there are currently two transcatheter valves available: the Edwards Sapien Valve and the Medtronic CoreValve. While similar in some design elements, they also have characteristic differences that affect both the mechanism of delivery as well as performance in patients. This review aims to take a closer look at the development of this new technology, review the published clinical results, and look toward the future of transcatheter valve therapeutics and the challenges therein. Lio, Antonio; Miceli, Antonio; Ferrarini, Matteo; Glauber, Mattia Little experience exists in minimally invasive treatment of double-valve disease. In this report, we present a minimally invasive approach for mitral and aortic valve disease through a minithoracotomy in the 3rd intercostal space with a sutureless aortic prosthesis implantation. © The Author 2016. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. Kanamori, Taro; Ichihara, Tetsuya; Sakaguchi, Hidehito; Inoue, Takehiko Aorto-left ventricular continuity destruction due to prosthetic valve endocarditis is rare, but it is one of the fatal complications after aortic root operation. We report a case of surgical treatment for prosthetic valve endocarditis after aortic root replacement. A 47-year-old man, who had undergone aortic root replacement with a composite graft was transferred to our hospital with sudden chest pain and high fever. Enhanced computed tomography showed a large space with contrast enhancement suggesting perivalvular leakage around the artificial composite graft. Emergency operation including aortic root re-replacement and reconstruction of the left ventricular outflow tract was performed successfully. We focused on its technical aspect. Elkharbotly, Ali; Delago, Augustin; El-Hajjar, Mohammad Transcatheter aortic valve replacement (TAVR) is well established for patients who cannot undergo surgery (Leon et al., N Engl J Med 2010;363:1597) or are high risk for surgery (Smith et al., N Engl J Med 2011;364:2187-2198). Experience with the TAVR procedure has led to recent reports of successful transcatheter mitral valve replacement (TMVR) procedures (Cheung et al., J Am Coll Cardiol 2014;64:1814; Seiffert et al., J Am Coll Cardiol Interv 2012;5:341-349) separately or simultaneously with the TAVR. However, these reports were of simultaneous valve-in-valve procedures (Cheung Anson, et al. J Am Coll Cardiol 2013;61:1759-1766). A recent report from Portugal also reported simultaneous transpical implantation of an inverted transcatheter aortic valve-in-ring in the mitral position and transcatheter aortic valve (Hasan et al., Circulation 2013;128:e74-e76). There has been an experience of TMVR only in native mitral valve for mitral valve stenosis, but none in both aortic and mitral valves. We report the first in human case of simultaneous transapical TAVR and TMVR in native valves secondary to valvular stenosis. Our patient was not a candidate for percutaneous balloon mitral valvuloplasty secondary to a high Wilkins Score. Sizing of the aortic valve was based on the transesophageal echocardiogram (TEE), whereas sizing of the mitral valve was based on TEE measurements and balloon inflation during left ventriculography. © 2015 Wiley Periodicals, Inc. Sogawa, M; Kasuya, S; Yamamoto, K; Koshika, M; Oguma, F; Hayashi, J Werner's syndrome is a rare genetic disease characterized by premature aging and scleroderma-like involvement of the skin. We report a case of aortic valve replacement for severely calcified aortic valve stenosis with a small annulus in a patient suffering from Werner's syndrome and liver cirrhosis Sehatzadeh, Shayan; Tu, Hong-Anh; Holubowich, Corinne; Higgins, Caroline Background Surgical aortic valve replacement (SAVR) is the gold standard for treating aortic valve stenosis. It is a major operation that requires sternotomy and the use of a heart-lung bypass machine, but in appropriately selected patients with symptomatic, severe aortic valve stenosis, the benefits of SAVR usually outweigh the harms. Transcatheter aortic valve implantation (TAVI) is a less invasive procedure that allows an artificial valve to be implanted over the poorly functioning valve. Methods We identified and analyzed randomized controlled trials that evaluated the effectiveness and safety of TAVI compared with SAVR or balloon aortic valvuloplasty and were published before September 2015. The quality of the body of evidence for each outcome was examined according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. The overall quality was determined to be high, moderate, low, or very low using a step-wise, structural methodology. We also developed a Markov decision-analytic model to assess the cost-effectiveness of TAVI compared with SAVR over a 5-year time horizon, and we conducted a 5-year budget impact analysis. Results Rates of cardiovascular and all-cause mortality were similar for the TAVI and SAVR groups in all studies except one, which reported significantly lower all-cause mortality in the TAVI group and a higher rate of stroke in the SAVR group. Trials of high-risk patients who were not suitable candidates for SAVR showed significantly better survival with TAVI than with balloon aortic valvuloplasty. Median survival in the TAVI group was 31 months, compared with 11.7 months in the balloon aortic valvuloplasty group. Compared with SAVR, TAVI was associated with a significantly higher risk of stroke, major vascular complications, paravalvular aortic regurgitation, and the need for a permanent pacemaker. SAVR was associated with a higher risk of bleeding. Transapical TAVI was associated with higher Kubota, Takehiro; Wakasa, Satoru; Shingu, Yasushige; Matsui, Yoshiro Unicuspid aortic valve in an adult is extremely rare. In addition, 90% of the patients with aortic coarctation are reported to die before the age 50. A 60-year-old woman was admitted to our hospital for further examination of exertional dyspnea which had begun one year before. She had been under medical treatment for hypertension since early thirties, and had been also diagnosed with moderate aortic stenosis at 50 years of age. She was at 1st diagnosed with aortic coarctation combined with bicuspid aortic valve stenosis. The aortic valve was then found unicuspid and was replaced under cardiopulmonary bypass with perfusion to both the ascending aorta and the femoral artery. Repair of aortic coarctation was performed 3 months later through left thoracotomy without extracorporeal circulation due to the rich collateral circulation. She had no postoperative complications, and hypertension as well as ankle-brachial index improved to the normal levels. Vola, Marco; Fuzellier, Jean-Francois; Kasra, Azarnoush; Morel, Jérôme; Campisi, Salvatore; Ruggeri, Gianvito; Favre, Jean Pierre The case is reported of a surgical aortic valvular stenosis with a severely calcified ascending aortic root in a 76-year-old woman. The morphology and size of the aortic annulus were unsuitable for transcatheter aortic valve implantation (TAVI); thus, surgery was scheduled. Aortic calcifications allowed a transverse aortotomy 4 cm superior to the sinotubular junction, with a remote endoaortic view of the valve. A Medtronic 3f Enable sutureless bioprosthesis was then implanted after aortic annular decalcification. Sutureless bioprostheses are new tools that promise to reduce technical difficulties and cross-clamp times in minimally invasive aortic valve replacement surgery. In addition, sutureless techniques may have other possible advantages in special circumstances requiring full sternotomy access, such as in the present case. Bashar, Abul Hasan Muhammad; Kazui, Teruhisa; Washiyama, Naoki; Yamashita, Katsushi; Terada, Hitoshi; Ohkura, Kazuhiro Prosthetic valve endocarditis is a relatively rare condition associated with high mortality. Endocarditis affecting 2 successive mechanical valves at the aortic position has not, to the best of our knowledge, been described. We reported such a patient whose condition was further complicated by mitral regurgitation, pulmonary hypertension, worsening heart failure, and cardiac conduction abnormalities. Considering the failure of 2 previous mechanical valves, we conducted a homograft replacement of the aortic root with coronary reattachment. Mitral regurgitation was treated by annuloplasty. The patient's early postoperative course was uneventful and he was doing well 16 months after surgery. We discuss the overall treatment strategy for recurrent prosthetic valve endocarditis and potential homograft advantages. Nistri, S; Sorbo, M; Marin, M; Palisi, M; Scognamiglio, R; Thiene, G OBJECTIVE—To evaluate the dimensions of the aortic root in a selected population of young males with isolated normally functioning bicuspid aortic valve. DESIGN AND SETTING—Echocardiographic and Doppler evaluation of conscripts with bicuspid aortic valve at the time of military pre-enrolment screening in two military hospitals. SUBJECTS AND METHODS—66 consecutive young men with a normally functioning bicuspid aortic valve were studied to assess aortic size at four aortic levels: annulus, sinuses of Valsalva, supra-aortic ridge, and proximal ascending aorta; 70 consecutive normal young subjects, matched for age and body surface area, were used as controls. RESULTS—In men with a bicuspid aortic valve, the diameter of the aortic root was significantly larger than in controls at the sinuses (3.16 (0.37) v 2.87 (0.31) cm, p < 0.001), at the supra-aortic ridge (2.64 (0.46) v 2.47 (0.28) cm, p = 0.01), and at the level of the proximal ascending aorta (3.12 (0.48) v 2.69 (0.28) cm, p < 0.001). The prevalence of aortic root dilatation was 7.5% at the annulus (5/66), 19.6% at the sinuses (13/66), 15% at the supra-aortic ridge (10/66), and 43.9% at the ascending aorta (29/66); 32 subjects (48%) had aortic root dimensions comparable with controls, while 34 (52%) had definitely abnormal aortic root dimensions. CONCLUSIONS—Aortic root enlargement in people with a bicuspid aortic valve occurs independently of haemodynamic abnormalities, age, and body size. However, there appear to be different subgroups of young adults with bicuspid aortic valves, one of which is characterised by aortic dilatation, possibly caused by a congenital abnormality of the aortic wall. Keywords: bicuspid aortic valve; aortic root dilatation PMID:10377302 Leung Wai Sang, Stephane; Bavaria, Joseph E; Giri, Jay S; Wickramasinghe, Rasi; Desai, Nimesh The presence of thoracic aortic aneurysms, particularly in the ascending aorta and arch, presents a challenge to transcatheter aortic valve replacement. We present a case of TAVR in the presence of a chronic ascending aortic aneurysm. doi: 10.1111/jocs.12724 (J Card Surg 2016;31:318-320). Minol, Jan-Philipp; Veulemans, Verena; Zeus, Tobias; Blehm, Alexander Transcatheter aortic valve implantation (TAVI) is an emerging treatment for high-risk patients with aortic stenosis. Aortic regurgitation is considered to be a relative contraindication for transcatheter procedures, as a non-calcified aortic annulus poses the risk of an insufficient anchoring of the transcatheter aortic valve prosthesis. Herein is described the case of a patient who suffered from recurrent aortic valve regurgitation after valve-sparing repair, and which was successfully treated by the transcatheter implantation of an Edwards SAPIEN 3™ prosthesis. This case report demonstrated the suitability of this prosthesis to treat pure aortic valve regurgitation, without excessive oversizing of the valve. Grbic, Saša; Ionasec, Razvan I.; Zäuner, Dominik; Zheng, Yefeng; Georgescu, Bogdan; Comaniciu, Dorin Aortic valve disorders are the most frequent form of valvular heart disorders (VHD) affecting nearly 3% of the global population. A large fraction among them are aortic root diseases, such as aortic root aneurysm, often requiring surgical procedures (valve-sparing) as a treatment. Visual non-invasive assessment techniques could assist during pre-selection of adequate patients, planning procedures and afterward evaluation of the same. However state of the art approaches try to model a rather short part of the aortic root, insufficient to assist the physician during intervention planning. In this paper we propose a novel approach for morphological and functional quantification of both the aortic valve and the ascending aortic root. A novel physiological shape model is introduced, consisting of the aortic valve root, leaflets and the ascending aortic root. The model parameters are hierarchically estimated using robust and fast learning-based methods. Experiments performed on 63 CT sequences (630 Volumes) and 20 single phase CT volumes demonstrated an accuracy of 1.45mm and an performance of 30 seconds (3D+t) for this approach. To the best of our knowledge this is the first time a complete model of the aortic valve (including leaflets) and the ascending aortic root, estimated from CT, has been proposed. Ranney, David N.; Williams, Judson B.; Wang, Andrew; Gaca, Jeffrey G. Background Transcatheter valve-in-valve (VIV) procedures are an alternative to standard surgical valve replacement in high risk patients. Methods Cases in which a commercially approved transcatheter aortic valve replacement (TAVR) device was used for a non-aortic VIV procedure between November 2013 and September 2015 are reviewed. Clinical, echocardiographic, and procedural details, patient survival, and symptom severity by NYHA class at follow-up were assessed. Results All patients were heart-team determined high-risk for conventional redo surgery (mean STS PROM = 6.8 ± 2.2%). Five patients underwent VIV replacement in the non-aortic position, 4 for bioprosthetic mitral valve dysfunction and one for bioprosthetic tricuspid valve dysfunction. Bioprosthetic failure was due to stenosis in 3 patients and regurgitation in 2 others. A balloon-expandable device was used for all patients (Edwards Lifesciences, Irvine, CA). Transcatheter VIV replacement was accomplished by the transapical (mitral) and transfemoral venous (tricuspid) approaches. Median post-operative length of stay was 5 days (range 3-12). No deaths occurred at a mean follow-up of 21 months. NYHA class at follow-up decreased from class IV at baseline to class I or II for all patients. No paravalvular leaks greater than trivial were encountered. Median mean gradient following mitral replacement was 6.5 mmHg (range 6-13 mmHg), and following tricuspid replacement was 4 mmHg. Post-operative complications included hematuria, epistaxis, acute kidney injury, and atrial fibrillation. Conclusions Transcatheter VIV implantation in the non-aortic position for dysfunctional bioprostheses can be performed safely with favorable clinical outcomes using a balloon expandable TAVR device. PMID:27059552 Swinkels, B.M.; Jaarsma, W.; Wely, L. Relik-van; van Swieten, H.A.; Ernst, J.M.P.G.; Plokker, H.W.M. This case report describes a patient with severe calcific aortic stenosis who was initially considered inoperable because of a very poor left ventricular function and severe pulmonary hypertension. After balloon aortic valvuloplasty, the clinical and haemodynamic status of the patient improved to such an extent that subsequent aortic valve replacement was considered possible and eventually proved to be successful. Balloon aortic valvuloplasty has value as a potential bridge to aortic valve replacement when the risks for surgery are considered to be too high. ImagesFigure 1 PMID:25696195 Craver, J M; Jones, E L; Hatcher, C R; Farmer, J H Twenty-six consecutive patients underwent combined aortic valve replacement and myocardial revascularization at the Emory University Affiliated Hospitals between May, 1973 and March, 1976. Acute myocardial infarction resulted in two operative deaths (8%). There have been four late deaths, all Class IV preoperative. The age range was 37 to 79 years with an average age of 60. Preoperatively all patients were Class IV or late Class III. Twenty-three patients had symptoms of angina pectoris; congestive heart failure was evident in 56%. Postoperatively, 70% are now Class 1 or II. Single coronary bypass was performed in 16 patients, double in 6, and triple in three. Double bypass plus mitral valve replacement was required in two with aneurysmectomy in one. The rate of intraoperative infarction was 27% for the series but only 7% in the last year. The methods of intraoperative myocardial preservation and the technical approach for the operative procedures were variable. Results with each method are correlated, and currently preferred techniques are presented and discussed. Best results were obtained in patients who presented early in their symptomatic course with isolated proximal coronary lesions and good renoff vessels. Excellent results could be achieved despite advanced age of patients, requirement for multiple bypass grafts, and correction of other associated cardiac lesions. Poorest results were obtained when long-standing ventricular failure was combined with poor vessels distal to coronary stenoses. PMID:860881 Klaaborg, Kaj Erik; Hjortdal, Vibeke; Nørgaard, Bjarne Linde; Terkelsen, Christian Juhl; Jensen, Kaare; Christiansen, Evald Høj; Terp, Kim Allan; Andersen, Gratien; Hvitfeldt, Steen; Andersen, Henning Rud Prosthetic valve endocarditis (PVE) after transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) is a potential life threatening complication. Better understanding of the incidence, predictors, clinical presentation, diagnostic measures, complications and management of PVE may help improve TAVI long-term outcome. We report a case of TAVI-PVE in an 80-year-old high risk patient in whom SAVR was successfully performed. We have reviewed literature regarding TAVI-PVE. PMID:27867590 Asgar, Anita W; Bonan, Raoul The field of transcatheter aortic valve implantation has been rapidly evolving. The Medtronic CoreValve first emerged on the landscape in 2004 with initial first human studies, and it is currently being studied in the Pivotal US trial. This article details the current experience with the self-expanding aortic valve with a focus on clinical results and ongoing challenges. Copyright © 2012 Elsevier Inc. All rights reserved. Takami, Yoshiyuki; Tajima, Kazuyoshi Limited data exis t on clinical relevance of aortic valve stenosis (AVS) and mitral annular calcification (MAC), although with similar pathophysiologic basis. We sought to reveal the prevalence of MAC and its clinical features in the patients undergoing aortic valve replacement (AVR) for AVS. We reviewed 106 consecutive patients who underwent isolated AVR from 2004 to 2010. Before AVR, CT scans were performed to identify MAC, whose severity was graded on a scale of 0-4, with grade 0 denoting no MAC and grade 4 indicating severe MAC. Echocardiography was performed before AVR and at follow-up over 2 years after AVR. MAC was identified in 56 patients with grade 1 (30 %), 2 (39 %), 3 (18 %), and 4 (13 %), respectively. Patients with MAC presented older age (72 ± 8 versus 66 ± 11 years), higher rate of dialysis-dependent renal failure (43 versus 4 %), and less frequency of bicuspid aortic valve (9 versus 36 %), when compared to those without MAC. No significant differences were seen in short- and mid-term mortality after AVR between the groups. In patients with MAC, progression of neither mitral regurgitation nor stenosis was observed at follow-up of 53 ± 23 months for 102 survivors, although the transmitral flow velocities were higher than in those without MAC. In conclusion, MAC represented 53 % of the patients undergoing isolated AVR for AVS, usually appeared in dialysis-dependent elder patients with tricuspid AVS. MAC does not affect adversely upon the survival, without progression of mitral valve disease, at least within 2 years after AVR. Pierard, Luc A; Dulgheru, Raluca Aortic valve disease and especially aortic stenosis (AS) is a growing cardiac pathology. Aortic valve replacement (AVR) is still the only treatment with proven benefit on survival in symptomatic patients and in patients with a left ventricular ejection fraction (LVEF) <50%. The benefit of prophylactic AVR in asymptomatic patients is still unproven. Once symptoms develop, the prognosis worsens. Exercise testing has emerged as a tool to unmask the "pseudo-asymptomatic" patients with AS (those without self-reporting symptoms), to link "exercise induced dyspnea" more confidently and more objectively to aortic valve disease and to allow for a safe "watchful waiting strategy" in "pseudo-symptomatic" patients (those with dyspnea unrelated to aortic valve disease). In cases in which exercise testing is unable to link dyspnea to aortic valve disease, exercise stress echocardiography and cardiopulmonary exercise testing may be helpful. Whatever the results of exercise testing with regard to symptom development, an increase in mean aortic valve pressure gradient >18-20 mmHg was associated with an increased risk of cardiac related events in severe AS patients (class IIb indication for AVR in the ESC guidelines). The decrease in LVEF during exercise as well as the development of exercise induced pulmonary hypertension, as revealed by exercise stress echocardiography, may be also useful in the risk stratification of these asymptomatic patients with severe AS. Data on the role of exercise echocardiography in asymptomatic severe aortic regurgitation patients is still scarce and further studies are needed. It seems that an exercise induced decrease in LVEF by 5% may be a better predictor of LV systolic dysfunction after AVR in asymptomatic patients or in patients with minimal symptoms. Exercise testing and exercise echocardiography are safe in the asymptomatic patients with aortic disease, provide useful clinical information that may help in risk assessment of these complicated Chester, Adrian H.; El-Hamamsy, Ismail; Butcher, Jonathan T.; Latif, Najma; Bertazzo, Sergio; Yacoub, Magdi H. The aortic valve lies in a unique hemodynamic environment, one characterized by a range of stresses (shear stress, bending forces, loading forces and strain) that vary in intensity and direction throughout the cardiac cycle. Yet, despite its changing environment, the aortic valve opens and closes over 100,000 times a day and, in the majority of human beings, will function normally over a lifespan of 70–90 years. Until relatively recently heart valves were considered passive structures that play no active role in the functioning of a valve, or in the maintenance of its integrity and durability. However, through clinical experience and basic research the aortic valve can now be characterized as a living, dynamic organ with the capacity to adapt to its complex mechanical and biomechanical environment through active and passive communication between its constituent parts. The clinical relevance of a living valve substitute in patients requiring aortic valve replacement has been confirmed. This highlights the importance of using tissue engineering to develop heart valve substitutes containing living cells which have the ability to assume the complex functioning of the native valve. PMID:25054122 Gasparović, Hrvoje; Zupancic-Salek, Silva; Brida, Vojtjeh; Dulić, Grgur; Jelić, Ivan Hemophilia A is an inherited bleeding disorder characterized by factor VIII deficiency. The basis for insufficient hemostasis lies within inadequate amplification of factor Xa production with the undersupplied factor VIII. We report on a young patient with critical aortic stenosis bearing all the clinical stigmata of severe hemophilia, in whom aortic valve replacement was performed with a tissue valve in order to avoid the need for long term anticoagulation. Ottervanger, J.P.; Thomas, K.; Sie, T.H.; Haalebos, M.M.P.; Zijlstra, F. Background Because of a high prevalence of coronary artery disease in patients with aortic valve disease, coronary angiography is recommended before aortic valve replacement. However, during the last three decades, a decline in mortality due to coronary heart disease has been observed in the general population in both Western Europe and the United States. It is unknown whether preoperative angiography is still mandatory in all patients. Aim To assess the prevalence of angiographically defined coronary artery disease in patients with aortic valve replacement and trends during a ten-year period. Methods We performed a retrospective cross-sectional study of patients undergoing aortic valve replacement between 1988 and 1998 in our institution. Patients with a history of coronary artery disease and patients younger than 25 years were excluded. Coronary atherosclerosis was defined as one or more coronary artery luminal stenosis of 50% or more on preoperative coronary angiography. Results During the study period 1339 patients had aortic valve replacement in our institution, data on 1322 (98%) were available for analysis. Previous coronary artery disease was documented in 124 patients (10%). After exclusion of 17 patients (no angiography), data on a total of 1181 patients were analysed. Coronary atherosclerosis was present in 472 patients (40%) on preoperative coronary angiography. Several well-known risk factors of ischaemic heart disease were associated with coronary atherosclerosis. The prevalence of angiographically defined coronary atherosclerosis varied between 30% and 50% per year. There was, however, no significant trend during the study period. Multivariate analyses, to adjust for potential differences in risk factors during the observation period, did not change this conclusion. Conclusions The prevalence of angiographically defined coronary artery disease in patients scheduled for aortic valve replacement is still high. From 1988 to 1998, no significant change Yosefy, Chaim; Berman, Michael; Beeri, Ronen A 28 year old woman underwent echocardiography following an incidental finding of a diastolic murmur. She has been taking phentermine for weight reduction for 8 months. Trans-esophageal echocardiography revealed a tear of the posterior cusp of the aortic valve causing severe regurgitation. Phentermine is known to cause valvular disease with prolonged use, but aortic valve rupture was not previously reported as a complication of phentermine valvulopathy. Nader, Joseph; Labont, Béatris Alina; Houpe, David; Caus, Thierry Anomalous origin of the left main coronary artery from the right coronary sinus is rarely diagnosed in elderly patients. We report such an anomaly in a 75-year-old lady presenting with chest pain and syncope. Preoperative screening revealed that her aortic valve was moderately stenotic. The patient underwent a successful unroofing procedure combined with aortic valve replacement. The outcome was uncomplicated and the patient remained asymptomatic at one year postoperatively. © The Author(s) 2014. Sitges, M.; Kapadia, S.; Rubin, D. N.; Thomas, J. D.; Tuzcu, M. E.; Lever, H. M. When left ventricular outflow tract obstruction develops after aortic valve replacement, few treatment choices have been available until now. We present a patient with prior aortic valve replacement who developed left ventricle outflow tract obstruction that was successfully treated with a percutaneous transcoronary myocardial septal alcohol ablation. This technique is a useful tool for the treatment of obstructive hypertrophic cardiomyopathy, especially in those patients with prior heart surgery. Copyright 2001 Wiley-Liss, Inc. Sitges, M.; Kapadia, S.; Rubin, D. N.; Thomas, J. D.; Tuzcu, M. E.; Lever, H. M. When left ventricular outflow tract obstruction develops after aortic valve replacement, few treatment choices have been available until now. We present a patient with prior aortic valve replacement who developed left ventricle outflow tract obstruction that was successfully treated with a percutaneous transcoronary myocardial septal alcohol ablation. This technique is a useful tool for the treatment of obstructive hypertrophic cardiomyopathy, especially in those patients with prior heart surgery. Copyright 2001 Wiley-Liss, Inc. David, Tirone E; David, Carolyn M; Manlhiot, Cedric; Colman, Jack; Crean, Andrew M; Bradley, Timothy In many cardiac units, aortic valve-sparing operations have become the preferred surgical procedure to treat aortic root aneurysm in patients with Marfan syndrome, based on relatively short-term outcomes. This study examined the long-term outcomes of aortic valve-sparing operations in patients with Marfan syndrome. All patients with Marfan syndrome operated on for aortic root aneurysm from 1988 through 2012 were followed prospectively for a median of 10 years. Follow-up was 100% complete. Time-to-event analyses were calculated using the Kaplan-Meier method with log-rank test for comparisons. A total of 146 patients with Marfan syndrome had aortic valve-sparing operations. Reimplantation of the aortic valve was performed in 121 and remodeling of the aortic root was performed in 25 patients. Mean age was 35.7 ± 11.4 years and two-thirds were men. Nine patients had acute, 2 had chronic type A, and 3 had chronic type B aortic dissections before surgery. There were 1 operative and 6 late deaths, 5 caused by complications of dissections. Mortality rate at 15 years was 6.8 ± 2.9%, higher than the general population matched for age and sex. Five patients required reoperation on the aortic valve: 2 for endocarditis and 3 for aortic insufficiency. Three patients developed severe, 4 moderate, and 3 mild-to-moderate aortic insufficiency. Rate of aortic insufficiency at 15 years was 7.9 ± 3.3%, lower after reimplantation than remodeling. Nine patients developed new distal aortic dissections during follow-up. Rate of dissection at 15 years was 16.5 ± 3.4%. Aortic valve-sparing operations in patients with Marfan syndrome were associated with low rates of valve-related complications in long-term follow-up. Residual and new aortic dissections were the leading cause of death. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. Weisburst, M R; Singh, A K; Riley, R S A case of aortic ball valve prosthesis malfunction is described in which the poppet became alternately stuck in the open and closed position. The patient experienced chest pain followed by pulmonary edema and cardiac arrest. Malfunction of prosthetic valve was diagnosed on echocardiogram and cardiopulmonary resuscitation was carried out until a Bjork-Shiley valve could be inserted in place of the faulty prosthesis. At the time of the operation, poppet migration had occurred and the poppet could not be found. Subsequent Bjork-Shiley aortic valve prosthesis dysfunction was suggested by variation in the intensity of the aortic opening sound and in the duration of the systolic ejection period. Fluoroscopy revealed the missing poppet in the left ventricle. Following surgical removal of the poppet, "normal" Bjork-Shiley valve function was restored. Ionasec, Razvan Ioan; Tsymbal, Alexey; Vitanovski, Dime; Georgescu, Bogdan; Zhou, S. Kevin; Navab, Nassir; Comaniciu, Dorin Disorders of the aortic valve represent a common cardiovascular disease and an important public-health problem worldwide. Pathological valves are currently determined from 2D images through elaborate qualitative evalu- ations and complex measurements, potentially inaccurate and tedious to acquire. This paper presents a novel diagnostic method, which identies diseased valves based on 3D geometrical models constructed from volumetric data. A parametric model, which includes relevant anatomic landmarks as well as the aortic root and lea ets, represents the morphology of the aortic valve. Recently developed robust segmentation methods are applied to estimate the patient specic model parameters from end-diastolic cardiac CT volumes. A discriminative distance function, learned from equivalence constraints in the product space of shape coordinates, determines the corresponding pathology class based on the shape information encoded by the model. Experiments on a heterogeneous set of 63 patients aected by various diseases demonstrated the performance of our method with 94% correctly classied valves. Brown, John W; Boyd, Jack H; Patel, Parth M; Baker, Mary L; Syed, Amjad; Ladowski, Joe; Corvera, Joel Transcatheter aortic valve replacement (TAVR) is currently offered to patients who are high-risk candidates for conventional surgical aortic valve replacement. For the past 37 years, off-pump aortic valve bypass (AVB) has been used in elderly patients at our center for this similarly high-risk group. Although TAVR and AVB were offered to similar patients at our center, comparisons of clinical outcomes and hospital economics for each strategy were not reported. We reviewed the clinical and financial records of 53 consecutive AVB procedures performed since 2008 with the records of 51 consecutive TAVR procedures performed since 2012. Data included demographics, hemodynamics, The Society of Thoracic Surgeons (STS) risk score, extent of coronary disease, and ventricular function. Follow-up was 100% in both groups. Hospital financial information for both cohorts was obtained. Mean risk score for the TAVR group was 10.1% versus 17.6% for AVB group (p < 0.001). Kaplan-Meier hospital rates of 3- and 6-month survival and of 1-year survival were 88%, 86%, 81%, and 61% and 89%, 83%, 83%, and 70% for the TAVR and AVB groups, respectively (p = 0.781). Two patients who had undergone TAVR had a procedure-related stroke. The one stroke in an AVB recipient was late and not procedure related. At discharge, mild and moderate perivalvular and central aortic insufficiency were present in 31% and 16% of TAVR recipients, respectively; no AVB valve leaked. Transvalvular gradients were reduced to less than 10 mm Hg in both groups. The average hospital length of stay for the AVB-treated patients was 13 days, and it was 9 days for the TAVR-treated patients. Median hospital charges were $253,000 for TAVR and $158,000 for AVB. Mean payment to the hospital was $65,000 (TAVR) versus $64,000 (AVB), and the mean positive contribution margin (profit) to the hospital was $14,000 for TAVR versus $29,000 for AVB. TAVR and AVB relieve aortic stenosis and have similar and acceptable procedural mortality Nascimbene, Angelo; Azpurua, Federico; Livesay, James J.; Fish, R. David We describe transcatheter aortic valve implantation in a patient who had severe peripheral artery disease. The patient's vascular condition required additional preliminary peripheral intervention to enable adequate vascular access. A 78-year-old man with severe aortic stenosis, substantial comorbidities, and severe heart failure symptoms was referred for aortic valve replacement. The patient's 20-mm aortic annulus necessitated the use of a 23-mm Edwards Sapien valve inserted through a 22F sheath, which itself needed a vessel diameter of at least 7 mm for percutaneous delivery. The left common femoral artery was selected for valve delivery. The left iliac artery and infrarenal aorta underwent extensive intervention to achieve an intraluminal diameter larger than 7 mm. After aortic valvuloplasty, valve deployment was successful, and the transaortic gradient decreased from 40 mmHg to less than 5 mmHg. The patient was discharged from the hospital 4 days postoperatively. We conclude that transcatheter aortic valve implantation can be successfully performed in patients with obstructed vascular access, including stenosis of the infrarenal aorta and the subclavian and coronary arteries. PMID:25873826 Bossé, Yohan; Huggins, Gordon S; Corte, Alessandro Della; Pibarot, Philippe; Michelena, Hector I.; Limongelli, Giuseppe; Boulanger, Marie‐Chloé; Evangelista, Arturo; Bédard, Elisabeth; Citro, Rodolfo; Body, Simon C; Nemer, Mona; Schoen, Frederick J Abstract Bicuspid aortic valve is the most prevalent cardiac valvular malformation. It is associated with a high rate of long‐term morbidity including development of calcific aortic valve disease, aortic regurgitation and concomitant thoracic aortic aneurysm and dissection. Recently, basic and translational studies have identified some key processes involved in the development of bicuspid aortic valve and its morbidity. The development of aortic valve disease and thoracic aortic aneurysm and dissection is the result of complex interactions between genotypes, environmental risk factors and specific haemodynamic conditions created by bicuspid aortic valve anatomy. Herein, we review the pathobiology of bicuspid aortic valve with a special emphasis on translational aspects of these basic findings. Important but unresolved problems in the pathology of bicuspid aortic valve and thoracic aortic aneurysm and dissection are discussed, along with the molecular processes involved. PMID:27499904 Choudhury, Arindam; Magoon, Rohan; Kapoor, Poonam Malhotra; Rajashekar, P. Aortic root surgical anatomy and knowledge of the various homograft implantation techniques is of paramount importance to the attending anesthesiologist for echocardiographic correlation, estimation and accurately predicting aortic annular dimensions for the valve replacement in a case of diseased homograft. PMID:27716714 Mokhles, M Mostafa; Rajeswaran, Jeevanantham; Bekkers, Jos A; Borsboom, Gerard J J M; Roos-Hesselink, Jolien W; Steyerberg, Ewout W; Bogers, Ad J J C; Takkenberg, Johanna J M; Blackstone, Eugene H This study describes echocardiographic allograft valve function over time in a cohort of patients who were prospectively followed after allograft aortic valve or root replacement, illustrating the use of longitudinal data analysis for assessing valve function over time. Serial, standardized echocardiographic measurements of aortic regurgitation, aortic gradient, annulus diameter, left ventricular outflow tract diameter, and aortic diameter in 301 hospital survivors (mean age, 46 years; range, 16-83 years) after allograft aortic valve (N=77) or root (N=224) replacement were analyzed using nonlinear longitudinal models. Aortic regurgitation increased over time. At 15 years, 41% of patients had at least moderate aortic regurgitation. Younger patient age and subcoronary implantation technique were associated with increased aortic regurgitation. Aortic gradient increased over time (from 9.4 mm Hg at 6 months to 21.3 mm Hg at 15 years); both initial and increase in aortic gradient were greater in younger patients and after subcoronary implantation technique. Annulus diameter slightly increased (from 21.9 mm at 6 months to 22.4 mm at 15 years), whereas aortic diameter slightly decreased over time (from 34.3 mm at 6 months to 32.7 mm at 15 years). Left ventricular outflow tract diameter remained constant at 22 mm. Younger patients in the subcoronary implantation group had a larger annulus diameter. Both aortic regurgitation and stenosis increase over time after allograft aortic valve or root replacement. Younger patient age and use of the subcoronary implantation technique are associated with increased regurgitation and stenosis. The use of nonlinear longitudinal models allows for an insightful analysis of allograft valve function over time. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved. Mokráček, Aleš; Kurfirst, Vojtěch Sutureless aortic valve replacement (AVR) was developed as an alternative treatment option to conventional open-heart surgery and transcatheter aortic valve implantation for “gray zone” patients. The need for concurrent mitral valve surgery is generally viewed as a contraindication to sutureless AVR. The purpose of this brief paper is to report our experiences with sutureless valves in patients after previous cardiac procedures with degenerated aortic bioprostheses and concomitant mitral valve disease. PMID:28096837 Neragi-Miandoab, Siyamek; Skripochnik, Edvard; Salemi, Arash; Girardi, Leonard The most widely used heart valve worldwide is the Edwards Sapien, which currently has 60% of the worldwide transcatheter aortic valve implantation (TAVI) market. The CoreValve is next in line in popularity, encompassing 35% of the worldwide TAVI market. Although these two valves dominate the TAVI market, a number of newer transcatheter valves have been introduced and others are in early clinical evaluation. The new valves are designed to reduce catheter delivery diameter, improve ease of positioning and sealing, and facilitate repositioning or removal. The most recent transcatheter valves for transapical use include Acurate TA (Symetis), Engager (Medtronic), and JenaValve the Portico (St Jude), Sadra Lotus Medical (Boston Scientific), and the Direct Flow Medical. These new inventions may introduce more effective treatment options for high-risk patients with severe aortic stenosis. Improvements in transcatheter valves and the developing variability among them may allow for more tailored approaches with respect to patient's anatomy, while giving operators the opportunity to choose devices they feel more comfortable with. Moreover, introducing new devices to the market will create a competitive environment among producers that will reduce high prices and expand availability. The present review article includes a discussion of recent patents related to Transcatheter Aortic Valves. Yao, Qingzhou; Song, Rui; Ao, Lihua; Cleveland, Joseph C; Fullerton, David A; Meng, Xianzhong Calcific aortic valve disease (CAVD) is a leading cardiovascular disorder in the elderly. Diseased aortic valves are characterized by sclerosis (fibrosis) and nodular calcification. Sclerosis, an early pathological change, is caused by aortic valve interstitial cell (AVIC) proliferation and overproduction of extracellular matrix (ECM) proteins. However, the mechanism of aortic valve sclerosis remains unclear. Recently, we observed that diseased human aortic valves overexpress growth factor neurotrophin 3 (NT3). In the present study, we tested the hypothesis that NT3 is a profibrogenic factor to human AVICs. AVICs isolated from normal human aortic valves were cultured in M199 growth medium and treated with recombinant human NT3 (0.10 µg/ml). An exposure to NT3 induced AVIC proliferation, upregulated the production of collagen and matrix metalloproteinase (MMP), and augmented collagen deposition. These changes were abolished by inhibition of the Trk receptors. NT3 induced Akt phosphorylation and increased cyclin D1 protein levels in a Trk receptor-dependent fashion. Inhibition of Akt abrogated the effect of NT3 on cyclin D1 production. Furthermore, inhibition of either Akt or cyclin D1 suppressed NT3-induced cellular proliferation and MMP-9 and collagen production, as well as collagen deposition. Thus, NT3 upregulates cellular proliferation, ECM protein production, and collagen deposition in human AVICs. It exerts these effects through the Trk-Akt-cyclin D1 cascade. NT3 is a profibrogenic mediator in human aortic valve, and overproduction of NT3 by aortic valve tissue may contribute to the mechanism of valvular sclerosis. Copyright © 2017 the American Physiological Society. Nowell, Justin L; Dewhurst, Alex; van Besouw, Jean-Pierre; Jahangiri, Marjan We describe a bailout procedure when surgical aortic-valve replacement was not possible due to severe calcification of the ascending aorta and the root and a very small annulus. A 21-mm CoreValve Revalving prosthesis was inserted via the aortotomy in the presence of a mitral prosthesis. Buellesfeld, Lutz; Gerckens, Ulrich; Grube, Eberhard Percutaneous aortic valve replacement is a new less-invasive alternative for high-risk surgical candidates with aortic stenosis. However, the clinical experience is still limited, and the currently available 'first-generation devices' revealed technical shortcomings, such as lack of repositionability and presence of paravalvular leakages. We report the first-in-man experience with the new self-expanding Lotus Valve prosthesis composed of a nitinol frame with implemented bovine pericardial leaflets which is designed to address these issues, being repositionable and covered by a flexible membrane to seal paravalvular gaps. We implanted this prosthesis in a 93-year old patient presenting with severe symptomatic aortic stenosis (valve area: 0.6 cm(2)). Surgical valve replacement had been declined due to comorbidities. We used a retrograde approach for insertion of the 21-French Lotus catheter loaded with the valve prosthesis via surgical cut-down to the external iliac artery. Positioning of the valve was guided by transesophageal echo and supra-aortic angiograms. The prosthesis was successfully inserted and deployed within the calcified native valve. Echocardiography immediately after device deployment showed a significant reduction of the transaortic mean pressure gradient (32 to 9 mmHg; final valve area 1.7 cm(2)) without evidence of residual aortic regurgitation. The postprocedural clinical status improved from NYHA-IV to NYHA-II. These results remained unchanged up to the 3 month follow-up. Successful percutaneous aortic valve replacement can be performed using the new self-expanding and repositionable Lotus valve for treatment of high-risk patients with aortic valve stenosis. Further studies are mandatory to assess device safety and efficacy in larger patient populations. Copyright 2008 Wiley-Liss, Inc. Eldar, M; Motro, M; Rath, S; Schy, N; Neufeld, H N Systolic closure of the aortic valve was found in 10 of 36 patients who underwent mitral valve replacement. Eight patients had early systolic closure, and two had mid-systolic closure. The left ventricular outflow tract dimension on M-mode and two dimensional echocardiograms, left ventricular posterior wall and septal thickness, left ventricular dimensions in systole and diastole, aortic valve opening, and mitral to aortic valve distance were not significantly different between patients with and without systolic closure of the aortic valve. Two of the 10 patients with systolic aortic valve closure were catheterised and in neither was there a gradient between the left ventricle and the aorta. The two patients with mid-systolic closure, however, were the patients who had the narrowest left ventricular outflow tract which could cause significant distortion of blood flow. Systolic closure of the aortic valve in patients with mitral valve replacement is probably not caused by left ventricular outflow tract obstruction, though abnormalities in laminar flow from the left ventricular outflow tract may be involved. Images PMID:7082513 Kurumisawa, Soki; Aizawa, Kei; Takazawa, Ippei; Sato, Hirotaka; Muraoka, Arata; Ohki, Shinnichi; Saito, Tsutomu; Kawahito, Koji; Misawa, Yoshio A 73-year-old woman on hemodialysis was transferred to our hospital for surgical treatment of heart valve disease. She required both mitral and aortic valve replacement with mechanical valves, associated with tricuspid annuloplasty. After aortic de-clamping, a massive hemorrhage from the posterior atrioventricular groove was observed. Under repeated cardiac arrest, the left atrium was reopened, the implanted mitral prosthetic valve was removed and a type I left ventricular rupture (Treasure classification) was diagnosed. The lesion was directly repaired with mattress stitches and running sutures, using reinforcement materials such as a glutaraldehyde-treated bovine pericardium. To avoid mechanical stress by the prosthetic valve on the repaired site, a mechanical valve was implanted using a translocation method. The patient suffered from aspiration pneumonia and disuse atrophy for 3 months. However, she was doing well at 1 year post-operation. Hinton, Robert B.; Adelman-Brown, Jennifer; Witt, Sandra; Krishnamurthy, Varun K.; Osinska, Hanna; Sakthivel, Bhuvaneswari; James, Jeanne F.; Li, Dean Y.; Narmoneva, Daria A.; Mecham, Robert P.; Benson, D. Woodrow Rationale Elastin is a ubiquitous extracellular matrix (ECM) protein that is highly organized in heart valves and arteries. Because elastic fiber abnormalities are a central feature of degenerative valve disease, we hypothesized that elastin deficient mice would manifest viable heart valve disease. Objective To analyze valve structure and function in elastin insufficient mice (Eln+/−) at neonatal, juvenile, adult and aged adult stages. Methods and Results At birth, histochemical analysis demonstrated normal ECM organization in contrast to the aorta. However, at juvenile and adult stages thin elongated valves with ECM disorganization, including elastin fragment infiltration of the annulus, were observed. The valve phenotype worsened by the aged adult stage with overgrowth and proteoglycan replacement of the valve annulus. The progressive nature of elastin insufficiency was also shown by aortic mechanical testing that demonstrated incrementally abnormal tensile stiffness from juvenile to adult stages. Eln+/− mice demonstrated increased valve interstitial cell (VIC) proliferation at the neonatal stage and varied VIC activation at early and late stages. Gene expression profile analysis identified decreased TGF-β mediated fibrogenesis signaling in Eln+/− valve tissue. Juvenile Eln+/− mice demonstrated normal valve function, but progressive valve disease (predominantly aortic regurgitation) was identified in 17% of adult and 70% of aged adult Eln+/− mice by echocardiography. Conclusions These results identify the Eln+/− mouse as a model of latent aortic valve disease and establish a role for elastin dysregulation in valve pathogenesis. PMID:20576933 Petit, Christopher J; Gao, Kevin; Goldstein, Bryan H; Lang, Sean M; Gillespie, Scott E; Kim, Sung-In H; Sachdeva, Ritu Aortic valve morphology has been invoked as intrinsic to outcomes of balloon aortic valvuloplasty (BAV) for congenital aortic valve stenosis. We sought to use aortic valve morphologic features to discriminate between valves that respond favorably or unfavorably to BAV, using aortic insufficiency (AI) as the primary outcome. All patients who underwent BAV at 2 large-volume pediatric centers from 2007 to 2014 were reviewed. Morphologic features assessed on pre-BAV echo included valve pattern (unicuspid, functional bicuspid, and true bicuspid), leaflet fusion length, leaflet excursion angle, and aortic valve opening area and on post-BAV echo included leaflet versus commissural tear. Primary end point was increase in AI (AI+) of ≥2°. Eighty-nine patients (median age 0.2 years) were included in the study (39 unicuspid, 41 functional bicuspid, and 9 true bicuspid valves). Unicuspid valves had a lower opening area (p <0.01) and greater fusion length (p = 0.01) compared with functional and true bicuspid valves. Valve gradient pre-BAV and post-BAV were not different among valve patterns. Of the 16 patients (18%) with AI+, 14 had leaflet tears (odds ratio 13.9, 3.8 to 50). True bicuspid valves had the highest rate (33%) of AI+. On multivariate analysis, leaflet tears were associated with AI+, with larger opening area pre-BAV and lower fusion length pre-BAV. AI+ was associated with larger pre-BAV opening area. Gradient relief was associated with reduced angle of excursion. Valve morphology influences outcomes after BAV. Valves with lesser fusion and larger valve openings have higher rates of leaflet tears which in turn are associated with AI. Finn, Matthew; Green, Philip In recent years, experience with transcatheter aortic valve implantation has led to improved outcomes in elderly patients with severe aortic stenosis (AS) who may not have previously been considered for intervention. These patients are often frail with significant comorbid conditions. As the prevalence of AS increases, there is a need for improved assessment parameters to determine the patients most likely to benefit from this novel procedure. This review discusses the diagnostic criteria for severe AS and the trials available to aid in the decision to refer for aortic valve procedures in the elderly. PMID:25216621 Merk, Denis R; Karar, Mohamed Esmail; Chalopin, Claire; Holzhey, David; Falk, Volkmar; Mohr, Friedrich W; Burgert, Oliver Aortic valve stenosis is one of the most frequently acquired valvular heart diseases, accounting for almost 70% of valvular cardiac surgery. Transapical transcatheter aortic valve implantation has recently become a suitable minimally invasive technique for high-risk and elderly patients with severe aortic stenosis. In this article, we aim to automatically define a target area of valve implantation, namely, the area between the coronary ostia and the lowest points of two aortic valve cusps. Therefore, we present a new image-based tracking method of these aortic landmarks to assist in the placement of aortic valve prosthesis under live 2D fluoroscopy guidance. We propose a rigid intensity-based image registration technique for tracking valve landmarks in 2D fluoroscopic image sequences, based on a real-time alignment of a contrast image including the initialized manual valve landmarks to each image of sequence. The contrast image is automatically detected to visualize aortic valve features when the aortic root is filled with a contrast agent. Our registration-based tracking method has been retrospectively applied to 10 fluoroscopic image sequences from routine transapical aortic valve implantation procedures. Most of all tested fluoroscopic images showed a successful tracking of valve landmarks, especially for the images without contrast agent injections. A new intraoperative image-based method has been developed for tracking aortic valve landmarks in live 2D fluoroscopic images to assist transapical aortic valve implantations and to increase the overall safety of surgery as well. Yoon, Sung-Han; Lefèvre, Thierry; Ahn, Jung-Ming; Perlman, Gidon Y; Dvir, Danny; Latib, Azeem; Barbanti, Marco; Deuschl, Florian; De Backer, Ole; Blanke, Philipp; Modine, Thomas; Pache, Gregor; Neumann, Franz-Josef; Ruile, Philipp; Arai, Takahide; Ohno, Yohei; Kaneko, Hidehiro; Tay, Edgar; Schofer, Niklas; Holy, Erik W; Luk, Ngai H V; Yong, Gerald; Lu, Qingsheng; Kong, William K F; Hon, Jimmy; Kao, Hsien-Li; Lee, Michael; Yin, Wei-Hsian; Park, Duk-Woo; Kang, Soo-Jin; Lee, Seung-Whan; Kim, Young-Hak; Lee, Cheol Whan; Park, Seong-Wook; Kim, Hyo-Soo; Butter, Christian; Khalique, Omar K; Schaefer, Ulrich; Nietlispach, Fabian; Kodali, Susheel K; Leon, Martin B; Ye, Jian; Chevalier, Bernard; Leipsic, Jonathon; Delgado, Victoria; Bax, Jeroen J; Tamburino, Corrado; Colombo, Antonio; Søndergaard, Lars; Webb, John G; Park, Seung-Jung Few studies have evaluated the clinical outcomes of transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve stenosis (AS). Particularly, limited data exist comparing the results of TAVR with new-generation devices versus early-generation devices. This study sought to evaluate the clinical outcomes of TAVR for bicuspid AS with early- and new-generation devices. The Bicuspid TAVR Registry is an international multicenter study enrolling consecutive patients with bicuspid AS undergoing TAVR between April 2005 and May 2015. Of 301 patients, 199 patients (71.1%) were treated with early-generation devices (Sapien XT [Edwards Lifesciences Corporation, Irvine, California]: n = 87; CoreValve [Medtronic, Minneapolis, Minnesota]: n = 112) and 102 with new-generation devices (Sapien 3 [Edwards Lifesciences Corporation]: n = 91; Lotus [Boston Scientific Corporation, Marlborough, Massachusetts]: n = 11). The mean Society of Thoracic Surgeons score was 4.7 ± 5.2 without significant differences between groups (4.6 ± 5.1 vs. 4.9 ± 5.4; p = 0.57). Overall, all-cause mortality rates were 4.3% at 30 days and 14.4% at 1 year. Moderate or severe paravalvular leak was absent and significantly less frequent with new-generation compared to early-generation devices (0.0% vs. 8.5%; p = 0.002), which resulted in a higher device success rate (92.2% vs. 80.9%; p = 0.01). There were no differences between early- and new-generation devices in stroke (2.5% vs. 2.0%; p > 0.99), life-threatening bleeding (3.5% vs. 2.9%; p > 0.99), major vascular complication (4.5% vs. 2.9%; p = 0.76), stage 2 to 3 acute kidney injury (2.5% vs. 2.9%; p > 0.99), early safety endpoints (15.1% vs. 10.8%; p = 0.30), and 30-day all-cause mortality (4.5% vs. 3.9%; p > 0.99). The clinical outcomes of TAVR in patients with bicuspid AS were favorable. New-generation devices were associated with less paravalvular leak and, hence, a higher device success rate than early Bharucha, Tara; Fernandes, Fernanda; Slorach, Cameron; Mertens, Luc; Friedberg, Mark Kevin Pressure gradient is used for timing of balloon aortic valvuloplasty for aortic stenosis (AS) in children, but does not correlate well with outcome and is limited if ventricular function is poor. In adults, effective orifice area (EOA) is used to assess AS severity, but EOA by continuity equation or 2D echo is unreliable in children. Three-dimensional echocardiography (3DE) may reliably assess EOA but has not been studied in children. We assessed measurement of aortic valve EOA by 3DE in children with AS before and after balloon aortic valvuloplasty and compared results with change in aortic valve gradient. 3DE was performed at time of catheterization before and after balloon aortic valvuloplasty. Using 3DE multiplanar review mode, valve annulus diameter, area, and EOA were measured and compared with change in aortic gradient and degree of aortic insufficiency. Twenty-four 3DE studies in 12 children (mean age 4.4 ± 5.0 years) were analyzed. EOA was measurable in all. Catheter peak gradient decreased from 45 ± 10 to 26 ± 17 mmHg (P = 0.0018). 3DE EOA increased after balloon aortic valvuloplasty (0.59 ± 0.52 cm(2) vs 0.80 ± 0.70 cm(2) ; P = 0.03), without change in valve diameter. EOA change correlated with change in peak (r = 0.77; P = 0.005) and mean (r = 0.60; P = 0.03) aortic valve gradient post balloon aortic valvuloplasty. 3DE facilitates EOA measurement in pediatric AS and correlates with change in aortic valve gradient after balloon valvuloplasty. © 2011, Wiley Periodicals, Inc. Raffa, Hassan; Al-Ibrahim, K.; Sorefan, A. Aniff; Narayanan, Lakshmi During reoperation for replacement of a regurgitant aortic bioprosthesis (a 23-mm bovine pericardial valve), it was judged that total removal of the valve would be difficult, and hazardous to the patient. Therefore, its leaflets were excised and its sewing ring left in situ. A 21-mm Carbomedics bileaflet mechanical valve was sutured to the bioprosthetic sewing ring and implanted in the orifice of the bioprosthesis, resulting in excellent hemodynamic performance. We report this new technique to illustrate its feasibility, safety, and efficiency, as an alternative to complete removal of defective prostheses in the aortic position. (Texas Heart Institute Journal 1991;18:199-201) Images PMID:15227480 Chiam, P T; Koh, T H; Chao, V T; Lee, C Y; See Tho, V Y; Tan, S Y; Lim, S T; Hwang, N C; Sin, Y K; Chua, Y L Surgical aortic valve replacement (AVR) is the standard of care for patients with symptomatic severe aortic stenosis (AS), providing relief of symptoms and prolonging survival. However, many patients are either denied or not offered surgery due to high surgical risk or non-operability for open AVR. The technology of percutaneous aortic valve implantation emerged in 2002, and has since evolved rapidly with satisfactory results. Currently, almost all the procedures are performed predominantly in Europe and North America. The first-in-Asia percutaneous transcatheter aortic valve implantation via the transfemoral route is described. A 77-year-old man with symptomatic severe AS and at high surgical risk was successfully treated, with sustained clinical improvement and satisfactory haemodynamic results at 30-day follow-up. Saikrishnan, Neelakantan; Yap, Choon-Hwai; Yoganathan, Ajit P. Bicuspid aortic valves (BAVs) are a congenital anomaly of the aortic valve with two fused leaflets, affecting about 1-2% of the population. BAV patients have much higher incidence of valve calcification & aortic dilatation, which may be related to altered mechanical forces from BAV hemodynamics. This study aims to characterize BAV hemodynamics using Particle Image Velocimetry(PIV). BAV models are constructed from normal explanted porcine aortic valves by suturing two leaflets together. The valves are mounted in an acrylic chamber with two sinuses & tested in a pulsatile flow loop at physiological conditions. 2D PIV is performed to obtain flow fields in three planes downstream of the valve. The stenosed BAV causes an eccentric jet, resulting in a very strong vortex in the normal sinus. The bicuspid sinus vortex appears much weaker, but more unstable. Unsteady oscillatory shear stresses are also observed, which have been associated with adverse biological response; characterization of the hemodynamics of BAVs will provide the first step to understanding these processes better. Results from multiple BAV models of varying levels of stenosis will be presented & higher stenosis corresponded to stronger jets & increased aortic wall shear stresses. Vora, Amit N; Gehrig, Thomas; Bashore, Thomas M; Kiefer, Todd L A 75-year old woman with a history of coronary disease status post 3-vessel coronary artery bypass grafting (CABG) 8 years ago and a repeat one-vessel CABG 2 years ago in the setting of aortic valve replacement with a #19 mm St. Jude bileaflet mechanical valve for severe aortic stenosis presented with two to three weeks of progressive dyspnea and increasing substernal chest discomfort. Echocardiography revealed a gradient to 31 mmHg across her aortic valve, increased from a baseline of 13 mmHg five months previously. Fluoroscopy revealed thrombosis of her mechanical aortic valve. She was not a candidate for surgery given her multiple comorbidities, and fibrinolysis was contraindicated given a recent subdural hematoma 1 year prior to presentation. She was treated with heparin and eptifibatide and subsequently demonstrated resolution of her aortic valve thrombosis. We report the first described successful use of eptifibatide in addition to unfractionated heparin for the management of subacute valve thrombosis in a patient at high risk for repeat surgery or fibrinolysis. Marasovic-Krstulovic, Daniela; Jurisic, Zrinka; Perkovic, Dijana; Aljinovic, Jure; Martinovic-Kaliterna, Dusanka We present a case of fulminant diffuse systemic sclerosis (dSSc) developed after the aortic valve replacement followed by fatal congestive heart failure within the 6 months from the initial symptoms. A 61-year-old male developed rapidly progressive diffuse systemic sclerosis following aortic valve replacement due to stenosis of bicuspid aortic valve. He presented with diarrhoea, weight loss, mialgia and arthralgia after cardiac surgery. Heart failure, due to myocardial fibrosis, was noted as a cause of death. We hypothesize that artificial materials like the ones used in mechanical valves or silicon materials in breast implants may induce fulminant course of pre-existing systemic sclerosis or create a new onset in predisposed individual. Copyright © 2014 Elsevier Ltd. All rights reserved. Chamandi, Chekrallah; Puri, Rishi; Rodriguez-Gabella, Tania; Rodés-Cabau, Josep Transcatheter aortic valve replacement (TAVR) is a well-established treatment for patients with severe symptomatic aortic stenosis who are at high or prohibitive surgical risk. More recently, TAVR has emerged as a valid alternative to surgical aortic valve replacement for treating intermediate-risk patients, and several studies are currently evaluating the role of TAVR in low-risk patients. Transcatheter heart valve (THV) technologies have evolved considerably over time, and important iterations have been implemented in many of the latest-generation devices to (1) reduce the size and improve delivery system properties; (2) improve valve deployment, repositioning, and retrievability; and (3) reduce paravalvular leaks. This article reviews the main characteristics of, and clinical results associated with, the newer-generation THVs while providing an overview of novel TAVR indications. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. Sehatzadeh, S; Doble, B; Xie, F; Blackhouse, G; Campbell, K; Kaulback, K; Chandra, K; Goeree, R Background One-year mortality outcomes in the PARTNER trial showed that transcatheter aortic valve implantation (TAVI) was noninferior to surgical aortic valve replacement (sAVR) in patients who were eligible for sAVR (cohort A), and superior to standard treatment in patients who were ineligible for sAVR (cohort B). Objective To update a previous report on the safety, effectiveness, and cost-effectiveness of TAVI, published in 2012. Data Sources A literature search was performed on September 11, 2012, using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published from January 1, 2011, until September 11, 2012. Review Methods Randomized controlled trials investigating TAVI in comparison to sAVR or standard treatment were included for analysis. Results were summarized descriptively. Results At 2-year follow-up, mortality in cohort A was similar between the TAVI and sAVR groups. Rates of stroke/transient ischemic attack, major vascular complications, and moderate/severe paravalvular aortic regurgitation were significantly higher in the TAVI group, but rate of major bleeding was significantly higher in the sAVR group. Mortality in cohort B was significantly lower with transfemoral (TF) TAVI than with standard treatment, but rate of stroke was significantly higher with TF TAVI. TF TAVI resulted in a more rapid improvement in quality of life scores than sAVR, but this difference was not sustained at 6 and 12 months. Patients who underwent transapical TAVI did not have a greater early improvement in quality of life compared to sAVR patients. Compared to standard treatment, TF TAVI resulted in a greater improvement in quality of life scores at all time points. Incremental cost-effectiveness ratios were in favour of TAVI for inoperable patients in the base-case analysis Neethling, W M; Papadimitriou, J M; Swarts, E; Hodge, A J Valve related factors and patient related factors are responsible for calcification of valvular bioprostheses. Recent studies showed different donor and recipient species have different influences on the total calcification rate of bioprostheses. This study was performed to evaluate and compare Kangaroo aortic valve leaflets with porcine aortic valve leaflets. Experimental design. Prospective study. Setting. Cardio-thoracic experimental research of a university department. Glutaraldehyde-fixed Kangaroo and porcine valve leaflets were evaluated in vitro according to valve geometry (internal diameter and leaflet thickness), morphology (light and electron microscopy) and tensile strength. In vivo evaluation consisted of implantation in a rat model for 8 weeks, Von Kossa stain for calcium and atomic absorption spectrophotometry for total extractable calcium content. Kangaroo valves indicated a smaller internal valve diameter as well as a thinner valve leaflet (p<0.01, ANOVA) at corresponding body weight, less proteoglycan spicules in the fibrosa, increased elasticity (p<0.05) and low calcification potential (p<0.01, confidence interval 95%). Kangaroo aortic valve leaflets have different valvular qualities compared to porcine valve tissue. Kangaroo valve leaflets are significantly superior to porcine valve leaflets as far as calcification is concerned. These results are encouraging and suggest further in vivo evaluation in a larger animal model before clinical application can be considered. Venardos, Neil; Bennett, Daine; Weyant, Michael J; Reece, Thomas Brett; Meng, Xianzhong; Fullerton, David A The aortic valve interstitial cell (AVIC) has been implicated in the pathogenesis of aortic stenosis. In response to proinflammatory stimulation, the AVIC undergoes a phenotypic change from that of a myofibroblast phenotype to that of osteoblast-like cell. Matrix Gla-protein (MGP) has been identified as an important inhibitor of vascular calcification. We therefore hypothesized that MGP expression is reduced in diseased AVICs, and loss of this protective protein contributes to calcification of the aortic valve. Our purpose was to compare MGP expression in normal versus diseased AVICs. Human AVICs were isolated from normal aortic valves from explanted hearts (n = 6) at the time of heart transplantation. AVICs were also isolated from calcified, diseased valves of patients (n = 6) undergoing aortic valve replacement. AVICs were grown in culture until they reached passages 2-6 before experimentation. Immunofluorescent staining, reverse transcriptase-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay were used to compare levels of MGP in normal and diseased AVICs. Statistics were performed using the Mann-Whitney U test (P < 0.05). MGP expression was significantly decreased in diseased AVICs relative to normal AVICs by immunofluorescent staining, reverse transcriptase-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay. An important anti-calcification defense mechanism is deficient in calcified aortic valves. MGP expression is significantly lower in diseased relative to normal AVICs. Lack of this important "anti-calcification" protein may contribute to calcification of the aortic valve. Copyright © 2015 Elsevier Inc. All rights reserved. Smith, Judith C. Beta-propiolactone sterilized, freeze-dried aortic valve homografts offer a dead framework which is accepted by the host and is capable of immediate and full function. The survival time of such grafts as fully functional units may be limited by physical and chemical alterations produced in the tissues by sterilization and freeze-drying. The organizing reaction of the host in covering the grafts or using them as a scaffolding may also be affected by these processes. It is possible that better long-term results may be achieved by using fresh grafts. There is no difference in host cellular response to fresh and sterilized and/or freeze-dried grafts. There is a possibility that heterogeneous reactions to polypeptides in the graft may occur in some individuals. Organization and covering of the graft by host tissue occurs from host tissues contiguous to the graft. Cells circulating in the bloodstream play no part in this by seeding on the surface. Thrombosis, in the absence of infection, is a rare complication. (Anticoagulants were not used in these patients.) Calcification occurs as only a late complication in persisting `dead' tissue. Unsuspected, and often extensive, myocardial ischaemia occurs frequently under bypass conditions with coronary artery perfusion and substantially contributes to immediate post-operative mortality and morbidity. Images PMID:6033379 Kim, Hyun-Jin; Kim, Kyung-Hee; Choi, Jae-Sung; Kim, Jun-Sung; Kim, Myung-A Preservation of the subvalvular apparatus has the merits of postoperative outcomes during mitral valve replacement for mitral regurgitation. We performed mitral valve replacement with anterior and posterior leaflet chordal preservation in a 65-year-old woman. On the 2nd postoperative day, routine postoperative trans-thoracic echocardiography showed an unknown aortic subvalvular mobile mass. We report a case of a remnant mitral subvalvular apparatus detected by echocardiography after chordal preserving mitral valve replacement which was confused with postoperative aortic valve vegetation. PMID:22509443 Hwang, You Mi; Kim, Jun; Lee, Ji Hyun; Kim, Minsu; Hwang, Jongmin; Kim, Joon Bum; Jung, Sung-Ho; Choo, Suk Jung; Nam, Gi Byoung; Choi, Kee Joon; Chung, Cheol Hyun; Lee, Jae Won; Kim, You Ho Conduction disturbances are common in patients with aortic stenosis. We investigated the incidence, reversibility, and prognosis of conduction disorders requiring permanent pacemaker implantation in patients with degenerative aortic stenosis after isolated aortic valve replacement. This was a retrospective study conducted at a tertiary care center. We evaluated the incidence of conduction disturbances in patients who underwent isolated surgical aortic valve replacement for aortic stenosis between January 2005 and May 2015. Relevant clinical information was obtained from the patients' medical records. We reviewed results of 663 patients with pathologically proven degenerative aortic stenosis (bicuspid aortic valve, n = 285 [43.0%]) who underwent isolated aortic valve replacement (mechanical valve, n = 310 [46.8%]). Patients' mean age was 67.1 ± 8.1 years, and 362 were male (54.6%). Immediate postoperative intraventricular conduction disorders occurred in 56 patients (8.4%), and atrioventricular block occurred in 68 patients (10.3%). Ten patients with symptomatic second-degree or third-degree atrioventricular block underwent permanent pacemaker implantation within 30 days of aortic valve replacement. During the mean follow-up period of 1288 ± 1122 days, 64 patients (9.7%) developed irreversible conduction disorders (bundle branch block n = 24 and first-degree atrioventricular block n = 42). Of the 10 patients requiring permanent pacemakers, 4 remained depend on the permanent pacemaker during follow-up. Beyond 30 days after aortic valve replacement, 1 patient underwent permanent pacemaker implantation for de novo conduction disturbance 44 months postoperatively. After isolated aortic valve replacement, permanent pacemaker implantation for conduction disturbance is rare (n = 10/663, 1.5%). Isolated aortic valve replacement for degenerative aortic stenosis has a low risk of conduction disturbances during long-term follow-up. Copyright © 2017 The Iwahashi, M; Nishimura, Y; Hiramatsu, K; Komori, S; Shibata, M; Yuzaki, M; Okamura, Y We performed aortic valve replacement in 24 patients aged over 70 with small calcified valves. The surgical management of such patients remains controversial as the extensive calcification compromises implantation. Hence, we used an ultrasonic debridement instrument to remove calcium and selected a small prosthesis with the largest possible orifice without enlargement of the aortic annulus. Echocardiography showed significant reductions in left ventricular mass index compared with preoperative values. Early and mid-term prognosis has been relatively good. Kunstadt, D; Adeyemo, A; Clauss, R H A bizarre mechanism of aortic valve incompetence was observed when the occluder of a Braunwald-Cutter aortic valve prosthesis decreased in diameter, volume, and weight, and from time to time fell into the left ventricle. The patient's symptoms were palpitation, coughing, chocking sensations, and fright. An operation disclosed a small, smooth ball with disrupted cloth on all the struts. The residual torn mesh was removed, and the ball was replaced. Neves, Paulo C; Paulo, Nelson Santos; Gama, Vasco; Vouga, Luís Transcatheter valve implantation offers a new treatment modality to those patients whose general condition makes conventional surgery very risky. However, the transcatheter option has only been available for the aortic valve. We describe a case of a successful implantation of two Edwards SAPIEN(®) 26 and 29 mm transapical valves, respectively, in aortic and mitral positions, on a 74-year-old patient with severe aortic and mitral stenosis. The procedure progressed uneventfully. Predischarge echocardiogram showed a peak aortic gradient of 20 mmHg, mild periprosthetic regurgitation, peak and mean mitral gradients of 12 and 4, respectively, and moderate (II/IV) periprosthetic regurgitation. Indications for transapical valve implantation will rapidly increase in the near future. It is essential to individualize the treatment be applied for each patient, in order to optimize the success of the procedure. Li, Ming; Mazilu, Dumitru; Horvath, Keith A This paper reports our work on developing a robotic surgical system for transapical beating heart aortic valve replacement (AVR) under interactive real-time magnetic resonance imaging (rtMRI) guidance. Our system integrates a real-time MRI system, a compound MRI robot, as well as an interface for the surgeon to plan the procedure and manipulate the robot. The compound robot consists of a positioning module and a valve delivery module. A 5-DOF Innomotion positioning arm provides and maintains direct access to the native aortic valve. A newly developed 3-DOF robotic valve delivery module allows the surgeon to remotely control bioprosthetic valve delivery with MRI guidance. Preliminary evaluation of the parameters of the robotic system demonstrates it can provide sufficient capability to successfully assist the surgeon. DiSesa, V J; Lachman, P; Collins, J J; Cohn, L H Improved assessment of valve area is essential to understanding the performance of prosthetic valves. The authors studied six patients undergoing aortic valve replacement using mechanical (ME) or porcine (PO) prostheses. Instantaneous cardiac output (CO) (L/min) was measured in the aorta using an ultrasonic flow probe. Left ventricular and aortic pressures (mmHg) were measured using Millar catheters. Data were analyzed using an IBM PC-AT. Valve area (cm2) was determined using Gorlin's formula (AG) and a new formula for instantaneous area derived mathematically and using a theoretic constant. AG, mean (AI) and peak (Apk) instantaneous areas were compared to geometric measures of area (Aactual) in vitro. Peak instantaneous area correlates best with measured area. Intraoperative assessment using the ultrasonic flow probe and computer analysis is helpful in understanding the dynamic properties of prosthetic valves in vivo. Darabant, Sergiu; Oberton, Shelby B; Roldan, Luis P; Roldan, Carlos A Aortic valve infective endocarditis (IE) can be complicated with severe aortic regurgitation (AR) jet-related lesions such as vegetations, pseudoaneurysms, aneurysms or perforations on the anterior mitral leaflet. Herein is reported the case of a 69-year-old male with culture-negative aortic valve endocarditis complicated with aortic valve perforations resulting in severe and eccentric AR and an AR jet-related ventricular septal defect (VSD). Neither transthoracic echocardiography (TTE) nor two-dimensional transesophageal echocardiography (2D-TEE) were unable to clearly discriminate an aorto-right ventricular fistula from a VSD. By contrast, three-dimensional TEE (3D-TEE) demonstrated multiple aortic valve vegetations, aortic valve perforations, severe AR, and an AR jet-related VSD. The 3D-TEE findings were confirmed at surgery, the aortic valve was replaced with a bioprosthetic valve, and the VSD was repaired with a pericardial patch. To the authors' knowledge, this is the first case of a VSD resulting from an AR jet lesion to be detected and characterized using 3D-TEE. The accurate preoperative diagnosis and characterization of the VSD with 3D-TEE contributed to successful surgery and the patient's short- and long-term survival. Video 1A: This four-chamber transthoracic echocardiography (TTE) view with color Doppler shows a color-Doppler jet traversing the basal interventricular septum (IVS) into the right ventricle, predominantly during systole. However, the origin of the jet resulting from an aortic-right ventricular fistula cannot be determined. A mild to moderate degree of tricuspid regurgitation is also noted. Video 1B: Close-up view of the basal IVS demonstrates a color Doppler jet traversing the IVS, predominantly during systole and apparently originating in the left ventricular outflow tract side, as illustrated by a color Doppler acceleration zone. However, and as in Fig. 1A, the origin of the jet resulting from an aortic-right ventricular fistula cannot Durmaz, Tahir; Ayhan, Huseyin; Keles, Telat; Aslan, Abdullah Nabi; Erdogan, Kemal Esref; Sari, Cenk; Bilen, Emine; Akcay, Murat; Bozkurt, Engin Transcatheter aortic valve replacement can be an effective, reliable treatment for severe aortic stenosis in surgically high-risk or ineligible patients. However, various sequelae like coronary artery obstruction can occur, not only in the long term, but also immediately after the procedure. We present the case of a 78-year-old woman whose left main coronary artery became obstructed with calculus 2 hours after the transfemoral implantation of an Edwards Sapien XT aortic valve. Despite percutaneous coronary intervention in that artery, the patient died. This case reminds us that early recognition of acute coronary obstruction and prompt intervention are crucial in patients with aortic stenosis who have undergone transcatheter aortic valve replacement. Yarbrough, William M; Mukherjee, Rupak; Ikonomidis, John S; Zile, Michael R; Spinale, Francis G Aortic valve stenosis is a common cause of left ventricular pressure overload, a pathologic process that elicits myocyte hypertrophy and alterations in extracellular matrix composition, both of which contribute to increases in left ventricular stiffness. However, clinical and animal studies suggest that increased myocardial extracellular matrix fibrillar collagen content occurs later in the time course of left ventricular pressure overload at a time coincident with severe abnormalities in diastolic function followed by the development of symptomatic heart failure. Aortic valve replacement remains the most effective treatment for elimination of chronic pressure overload secondary to aortic stenosis but has traditionally been recommended only after the onset of clinical symptoms. Long-term follow-up of patients with symptomatic aortic stenosis after aortic valve replacement suggests that valve replacement may not result in complete reversal of the maladaptive changes that occur within the myocardial extracellular matrix secondary to the pressure overload state. To the contrary, residual left ventricular extracellular matrix abnormalities such as these are likely responsible for persistent abnormalities in diastolic function and increased morbidity and mortality after aortic valve replacement. Defining the mechanisms and pathways responsible for regulating the myocardial extracellular matrix during the natural history of aortic stenosis may provide a means by which to detect crucial structural milestones and thereby permit more precise identification of the development of maladaptive left ventricular remodeling. Published by Mosby, Inc. Kim, Kyung Hwa; Choi, Jong Bum; Kim, Min Ho; Kim, Won Ho; Lee, Mi Kyung; Lee, Sam Youn Valve replacement is typically the most appropriate option for treating aortic valve stenotic insufficiency. However, neither mechanical nor bioprosthetic replacement components preserve the circumferential expansion and contraction of a native aortic annulus during the cardiac cycle, because the prosthetic ring is affixed to the annulus. A 64-year-old man presented with a bicuspid and stenotic aortic valve, and the native annulus was too small to accommodate a porcine replacement valve. We fashioned new aortic leaflets from bovine pericardium with use of a template, and we affixed the sinotubular junction with use of inner and outer stabilization rings. Postoperative echocardiograms revealed coaptation of the 3 new leaflets with no regurgitation. At the patient's 5.5-year follow-up examination, echocardiograms showed flexible leaflet movement with a coaptation height of 7 mm, and expansion and contraction of the aortic annulus similar to that of a normal native annulus. The transvalvular pressure gradient was insignificant. If long-term durability of the new leaflets is confirmed, this method of leaflet replacement and fixation of the sinotubular junction might serve as an acceptable alternative to valve replacement in the treatment of aortic valve stenosis. We describe the patient's case and present our methods and observations. Kim, Kyung Hwa; Kim, Min Ho; Kim, Won Ho; Lee, Mi Kyung; Lee, Sam Youn Valve replacement is typically the most appropriate option for treating aortic valve stenotic insufficiency. However, neither mechanical nor bioprosthetic replacement components preserve the circumferential expansion and contraction of a native aortic annulus during the cardiac cycle, because the prosthetic ring is affixed to the annulus. A 64-year-old man presented with a bicuspid and stenotic aortic valve, and the native annulus was too small to accommodate a porcine replacement valve. We fashioned new aortic leaflets from bovine pericardium with use of a template, and we affixed the sinotubular junction with use of inner and outer stabilization rings. Postoperative echocardiograms revealed coaptation of the 3 new leaflets with no regurgitation. At the patient's 5.5-year follow-up examination, echocardiograms showed flexible leaflet movement with a coaptation height of 7 mm, and expansion and contraction of the aortic annulus similar to that of a normal native annulus. The transvalvular pressure gradient was insignificant. If long-term durability of the new leaflets is confirmed, this method of leaflet replacement and fixation of the sinotubular junction might serve as an acceptable alternative to valve replacement in the treatment of aortic valve stenosis. We describe the patient's case and present our methods and observations. PMID:24512414 Baron, Suzanne J.; Arnold, Suzanne V.; Herrmann, Howard C.; Holmes, David; Szeto, Wilson Y.; Allen, Keith B.; Chhatriwalla, Adnan K.; Vemulapali, Sreekaanth; O’Brien, Sean; Dai, Dadi; Cohen, David J. Background In patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), prior studies have suggested that reduced left ventricular ejection fraction (LVEF) and low aortic valve gradient (AVG) are associated with worse long-term outcomes. Since these conditions commonly coexist, the extent to which they are independently associated with outcomes after TAVR is unknown. Objectives To evaluate the impact of LVEF and AVG on clinical outcomes after TAVR and to determine whether the effect of AVG on outcomes is modified by LVEF. Methods Using data from 11,292 patients who underwent TAVR as part of the TVT Registry, we examined rates of 1-year mortality and recurrent heart failure in patients with varying levels of LV dysfunction (LVEF < 30% vs. 30–50% vs. > 50%) and AVG (< 40mmHg vs. ≥ 40mmHg). Multivariable models were used to estimate the independent effect of AVG and LVEF on outcomes. Results Over the first year of follow-up after TAVR, patients with LV dysfunction and low AVG had higher rates of death and recurrent heart failure. After adjustment for other clinical factors, only low AVG was associated with higher mortality (HR 1.21, 95% CI 1.11–1.32; p < 0.001) and higher rates of heart failure (HR 1.52; 95% CI 1.36–1.69; p < 0.001), whereas the effect of LVEF was no longer significant. There was no evidence of effect modification between AVG and LVEF with respect to either endpoint. Conclusion In this large series of real world patients undergoing TAVR, low AVG, but not LV dysfunction, was associated with higher rates of mortality and recurrent heart failure. Although these findings suggest that AVG should be considered when evaluating the risks and benefits of TAVR for individual patients, neither severe LV dysfunction nor low AVG alone or in combination provide sufficient prognostic discrimination to preclude treatment with TAVR. PMID:27199058 Gessat, Michael; Merk, Denis R.; Falk, Volkmar; Walther, Thomas; Jacobs, Stefan; Nöttling, Alois; Burgert, Oliver Stenosis of the aortic valve is a common cardiac disease. It is usually corrected surgically by replacing the valve with a mechanical or biological prosthesis. Transapical aortic valve implantation is an experimental minimally invasive surgical technique that is applied to patients with high operative risk to avoid pulmonary arrest. A stented biological prosthesis is mounted on a catheter. Through small incisions in the fifth intercostal space and the apex of the heart, the catheter is positioned under flouroscopy in the aortic root. The stent is expanded and unfolds the valve which is thereby implanted into the aortic root. Exact targeting is crucial, since major complications can arise from a misplaced valve. Planning software for the perioperative use is presented that allows for selection of the best fitting implant and calculation of the safe target area for that implant. The software uses contrast enhanced perioperative DynaCT images acquired under rapid pacing. In a semiautomatic process, a surface segmentation of the aortic root is created. User selected anatomical landmarks are used to calculate the geometric constraints for the size and position of the implant. The software is integrated into a PACS network based on DICOM communication to query and receive the images and implants templates from a PACS server. The planning results can be exported to the same server and from there can be rertieved by an intraoperative catheter guidance device. Spaziani, Gaia; Ballo, Piercarlo; Favilli, Silvia; Fibbi, Veronica; Buonincontri, Lorenzo; Pollini, Iva; Zuppiroli, Alfredo; Chiappa, Enrico The aim of this study was to explore the medium-term clinical outcome and the risk of progression of aortic valve disease and aortic dilation in pediatric patients with isolated bicuspid aortic valve (BAV). 179 pediatric patients with isolated BAV were prospectively followed from January 1995 to December 2010. Patients with severe valve dysfunction at baseline were excluded. Clinical outcome included cardiac death, infective endocarditis, aortic complications, cardiac surgery and percutaneous valvuloplasty. Echocardiographic endpoints were: progression of aortic stenosis (AS) or regurgitation (AR) and progressive aortic enlargement at different levels of the aortic root, evaluated as z-score. The median age at diagnosis was 7.8 [2.7-12.0] years. After a median followup of 5.4 [2.3-9.2] years, all patients were alive. The clinical endpoint occurred in 4 (2.2 %) patients (0.41 events per 100 patient-years). A progression of AS and AR was observed in 9 (5.0 %) and 29 (16.2 %) patients, respectively. The z-scores at the end of follow-up were not significantly different from baseline at the annulus, Valsalva sinuses and sinotubular junction, whereas a slight increase was observed at the level of the ascending aorta (1.9 vs 1.5, p = 0.046). Significant progressive aortic dilation occurred in a minority of patients (10.6, 5.6, 9.5, and 19.0 % respectively). The clinical outcome in pediatric patients with isolated BAV is favourable and the progression of aortic valve dysfunction and aortic dilation is relatively slow. These findings may be taken into account to better guide risk assessment and clinical follow-up in these patients. Webb, John G; Munt, Bradley; Makkar, Raj R; Naqvi, Tasneem Z; Dang, Ninh The objective of this study was to develop a prosthetic cardiac valve designed for percutaneous transcatheter implantation. Percutaneous catheter-based therapies play a limited role in the management of cardiac valve disease. Surgical implantation of prosthetic valves usually requires thoracotomy and cardiopulmonary bypass. The stent-valve is constructed of a rolled sheet of heat-treated nitinol. Although malleable when cooled, once released from a restraining sheath at body temperature the stent unrolls, becomes rigid, and assumes its predetermined cylindrical conformation. A ratcheting lock-out mechanism prevents recoil and external protrusions facilitate anchoring. Valve leaflets are constructed of bovine pericardium. The feasibility of catheter implantation, prosthetic valve function, and survival were investigated in an animal model. In vitro and pulse duplicator testing documented valve durability. Endovascular delivery of the prototype stent-valve to the aortic or pulmonary position was feasible. Accurate positioning was required to ensure exclusion of the native valve leaflets and, in the case of the aortic valve, to avoid compromise of the coronary ostia or mitral apparatus. Oversizing of the stent in relation to the valve annulus was desirable to facilitate anchoring and prevent paravalvular insufficiency. Stent-valve implantation proved feasible and compatible with survival in an animal model. Transcatheter implantation of prosthetic valves is possible. Further evolution of this technology will involve lower-profile devices with design features that facilitate vascular delivery, visualization, positioning, deployment, and valvular function. Chu, Yi; Lund, Donald D; Doshi, Hardik; Keen, Henry L; Knudtson, Kevin L; Funk, Nathan D; Shao, Jian Q; Cheng, Justine; Hajj, Georges P; Zimmerman, Kathy A; Davis, Melissa K; Brooks, Robert M; Chapleau, Mark W; Sigmund, Curt D; Weiss, Robert M; Heistad, Donald D Hypercholesterolemia and hypertension are associated with aortic valve stenosis (AVS) in humans. We have examined aortic valve function, structure, and gene expression in hypercholesterolemic/hypertensive mice. Control, hypertensive, hypercholesterolemic (Apoe(-/-)), and hypercholesterolemic/hypertensive mice were studied. Severe aortic stenosis (echocardiography) occurred only in hypercholesterolemic/hypertensive mice. There was minimal calcification of the aortic valve. Several structural changes were identified at the base of the valve. The intercusp raphe (or seam between leaflets) was longer in hypercholesterolemic/hypertensive mice than in other mice, and collagen fibers at the base of the leaflets were reoriented to form a mesh. In hypercholesterolemic/hypertensive mice, the cusps were asymmetrical, which may contribute to changes that produce AVS. RNA sequencing was used to identify molecular targets during the developmental phase of stenosis. Genes related to the structure of the valve were identified, which differentially expressed before fibrotic AVS developed. Both RNA and protein of a profibrotic molecule, plasminogen activator inhibitor 1, were increased greatly in hypercholesterolemic/hypertensive mice. Hypercholesterolemic/hypertensive mice are the first model of fibrotic AVS. Hypercholesterolemic/hypertensive mice develop severe AVS in the absence of significant calcification, a feature that resembles AVS in children and some adults. Structural changes at the base of the valve leaflets include lengthening of the raphe, remodeling of collagen, and asymmetry of the leaflets. Genes were identified that may contribute to the development of fibrotic AVS. © 2016 American Heart Association, Inc. Straneo, Pablo; Parma, Gabriel; Lluberas, Natalia; Marichal, Alvaro; Soca, Gerardo; Cura, Leandro; Paganini, Juan J; Brusich, Daniel; Florio, Lucia; Dayan, Victor Background Bicuspid aortic valve patients have an increased risk of aortic dilatation. A deficit of nitric oxide synthase has been proposed as the causative factor. No correlation between flow-mediated dilation and aortic diameter has been performed in patients with bicuspid aortic valves and normal aortic diameters. Being a hereditary disease, we compared echocardiographic features and endothelial function in these patients and their first-degree relatives. Methods Comprehensive physical examinations, routine laboratory tests, transthoracic echocardiography, and measurements of endothelium-dependent and non-dependent flow-mediated vasodilatation were performed in 18 bicuspid aortic valve patients (14 type 1 and 4 type 2) and 19 of their first-degree relatives. Results The first-degree relatives were younger (36.7 ± 18.8 vs. 50.5 ± 13.9 years, p = 0.019) with higher ejection fractions (64.6% ± 1.7% vs. 58.4% ± 9.5%, p = 0.015). Aortic diameters indexed to body surface area were similar in both groups, the except the tubular aorta which was larger in bicuspid aortic valve patients (19.3 ± 2.7 vs. 17.4 ± 2.2 mm·m(-2), p = 0.033). Flow-dependent vasodilation was similar in both groups. A significant inverse correlation was found between non-flow-dependent vasodilation and aortic root diameter in patients with bicuspid aortic valve ( R = -0.57, p = 0.05). Conclusions Bicuspid aortic valve patients without aortopathy have larger ascending aortic diameters than their first-degree relatives. Endothelial function is similar in both groups, and there is no correlation with ascending aorta diameter. Nonetheless, an inverse correlation exists between non-endothelial-dependent dilation and aortic root diameter in bicuspid aortic valve patients. Von Oppell, U O; Stemmet, F; Levetan, B; Heijke, S A; Brink, J Short-term results of the bioprosthetic Biocor No-React composite porcine stentless aortic valve (Biocor Industria e Pesquisas LTDA, Belo Horizonte, Brazil) implanted in patients in whom anticoagulation was thought to be contraindicated or expected to be non-compliant. Retrospective review of 52 consecutive prospective patients in whom this valve was implanted, between September 1994 and May 1998. Average age was 44 +/- 17 years; 75% of patients were operated on for rheumatic heart disease and combined procedures were done in 40% of cases. Early mortality was 5.8%, and related to pre-operative ejection fraction ( P < 0.03), New York Heart Association (NYHA) class (P < 0.01), and bacterial endocarditis (P < 0.04). On discharge, 84% of survivors were in NYHA class I and 16% in class II. The average postoperative prosthetic valve peak gradient on echocardiography was 19.9 +/- 11 mmHg and was related to pre-operative ejection fraction and smaller valve sizes. Postoperative residual trivial or mild aortic regurgitation was seen in 19 patients (36.6%), resolved on follow-up in 10 cases, and did not correlate with structural deterioration, re-operation, mortality, or widening of the non-coronary sinus. The non-coronary aortic sinus was widened on closure, because of perceived crowding of the adjacent stentless valve commisures, in 52% of cases. This was thought to be related to the use of an oblique as opposed to transverse aortotomy. Patient survival, inclusive of operative deaths, was 88.5%, and event-free survival was 80.0% at 4 years. The short-term results of this stentless aortic valve in a young predominantly third-world population group are acceptable, and appear to be superior to the results for mechanical valves in a similar patient group. We would recommend a transverse aortotomy above the sinotubular ridge to be the more appropriate aortotomy incision when using stentless aortic valves. Salinas, Pablo; Moreno, Raúl; Calvo, Luis; Sánchez-Recalde, Ángel; Jiménez-Valero, Santiago; Galeote, Guillermo; López-Fernández, Teresa; Ramírez, Ulises; Riera, Luis; Plaza, Ignacio; Moreno, Isidro; Mesa, José María; López-Sendón, José Luis Transcatheter aortic valve implantation is used as an alternative to surgical valve replacement in patients with severe aortic stenosis who are considered high-surgical-risk or inoperable. Two of the main areas of uncertainty in this field are valve durability and long-term survival. This prospective single-center registry study from a tertiary hospital included all consecutive patients who underwent percutaneous aortic valve implantation between 2008 and 2012. Clinical follow-up lasted a minimum of 2.5 years and a maximum of 6.5 years. Valve Academic Research Consortium-2 definitions were used. Seventy-nine patients were included, with an immediate success rate of 94.9%. The median survival was 47.6 months (95% confidence intervals, 37.4-57.9 months), ie, 4 years. One quarter of deaths occurred in the first month, and most were of cardiovascular cause. After the first month, most deaths were due to noncardiovascular causes. The mean values of valve gradients did not increase during follow-up. The cumulative rate of prosthetic valve dysfunction was 15.3%, with no cases of repeat valve replacement. Half of the patients with aortic stenosis who underwent transcatheter aortic valve implantation were alive 4 years after the procedure. There was a 15.3% prosthetic valve dysfunction rate in cumulative follow-up, with no cases of repeat valve replacement. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved. Zhou, Hua-song; Gu, Chun-hu; Chen, Wen-sheng; Zhao, Jin-chao; Wang, Yun-ya; Tan, Hong-mei; Yi, Ding-hua To prepare a porcine aortic valve (PAV) free of the cellular components. The cellular components of porcine PAV were completely removed using trypsin and Triton X-100, and the acellular PAV was examined microscopically with HE staining with its physical and chemical properties assessed. Transmission electron microscopy was used to observe the integrity of the collagen and elastin and the DNA contents in the PAV was detected to confirm the total removal of the cellular components. With the fresh PAV as the control, small pieces of the acellular PAV were implanted into the subcutaneous tissues of 4 rabbits, and 4 weeks after the implantation, the implants were harvested for microscopic observation. The cellular components were effectively removed from the cusps and roots of the PAV by trypsin and TritonX-100, with marked soluble protein loss [(0.24-/+0.04)% vs (0.48-/+0.12)%] and significantly increased water content [(92.2-/+1.5)% vs (89.2-/+1.6)%]. The acellular PAV still maintained good fibrous scaffold structure and the shrinkage temperature and tension at fracture underwent no significantly changes [(67.9-/+1.0) degrees celsius; vs (68.8-/+0.8) degrees celsius; and (489.3-/+19.0) g/mm2 vs (540.7-/+19.5) g/mm2, respectively]. The PAVs implanted in rabbits showed only mild tissue reaction with a few infiltrating neutrophils, lymphocytes and plasmocytes observed 4 weeks later. The accelular PAV caused obviously milder inflammatory reactions than fresh PAV. The acellular PAV prepared by treatment with trypsin and Triton X-100 retains good fibrous scaffold structure and mechanical strength with low antigenicity. van Kesteren, F; Wiegerinck, E M A; Rizzo, S; Baan, J; Planken, R N; von der Thüsen, J H; Niessen, H W M; van Oosterhout, M F M; Pucci, A; Thiene, G; Basso, C; Sheppard, M N; Wassilew, K; van der Wal, A C Autopsy after transcatheter aortic valve implantation (TAVI) is a new field of interest in cardiovascular pathology. To identify the cause of death, it is important to be familiar with specific findings related to the time interval between the procedure and death. We aimed to provide an overview of the autopsy findings in patients with TAVI in their medical history divided by the timing of death with specific interest in the added value of autopsy over a solely clinically determined cause of death. In 8 European centres, 72 cases with autopsy reports were available. Autopsies were divided according to the time interval of death and reports were analysed. In 32 patients who died ≤72 h postprocedure, mortality resulted from cardiogenic or haemorrhagic shock in 62.5 and 34.4%, respectively. In 31 patients with mortality >72 h to ≤30 days, cardiogenic shock was the cause of death in 51.6% followed by sepsis (22.6%) and respiratory failure (9.7%). Of the nine patients with death >30 days, 88.9% died of sepsis, caused by infective endocarditis in half of them. At total of 12 patients revealed cerebrovascular complications. Autopsy revealed unexpected findings in 61.1% and resulted in a partly or completely different cause of death as was clinically determined. Autopsy on patients who underwent TAVI reveals specific patterns of cardiovascular pathology that clearly relate to the time interval between TAVI and death and significantly adds to the clinical diagnosis. Our data support the role of autopsy including investigation of the cerebrum in the quickly evolving era of cardiac device technology. Wöhrle, Jochen; Gonska, Birgid; Rodewald, Christoph; Seeger, Julia; Scharnbeck, Dominik; Rottbauer, Wolfgang Aims The third generation Edwards Sapien 3 (Edwards Lifesciences Inc., Irvine, California) system was optimized to reduce residual aortic regurgitation and vascular complications. Methods and Results 235 patients with severe symptomatic aortic stenosis were prospectively enrolled. Transcatheter aortic valve implantations (TAVI) were performed without general anesthesia by transfemoral approach. Patients were followed for 30 days. Patients received 23mm (N = 77), 26mm (N = 91) or 29mm (N = 67) valve based on pre-procedural 256 multislice computer tomography. Mean oversizing did not differ between the 3 valves. There was no residual moderate or severe aortic regurgitation. Rate of mild aortic regurgitation and regurgitation index did not differ between groups. There was no switch to general anesthesia or conversion to surgery. Rate of major vascular complication was 3.0% with no difference between valve and delivery sheath sizes. Within 30 days rates of all cause mortality (2.6%) and stroke (2.1%) were low. Conclusions In patients with severe aortic stenosis transfemoral TAVI with the Edwards Sapien 3 valve without general anesthesia was associated with a high rate of device success, no moderate or severe residual aortic regurgitation, low rates of major vascular complication, mortality and stroke within 30 days with no difference between the 3 valve sizes. Trial Registration ClinicalTrials.gov NCT02162069 PMID:27003573 Watanabe, Yusuke; Morice, Marie-Claude; Bouvier, Erik; Leong, Tora; Hayashida, Kentaro; Lefèvre, Thierry; Hovasse, Thomas; Romano, Mauro; Chevalier, Bernard; Donzeau-Gouge, Patrick; Farge, Arnaud; Cormier, Bertrand; Garot, Philippe This study sought to evaluate the accuracy, reproducibility, and predictive value for post-procedural aortic regurgitation (AR) of an automated multidetector computed tomography (MDCT) post-processing imaging software, 3mensio Valves (version 5.1.sp1, 3mensio Medical Imaging BV, the Netherlands), in the assessment of patients undergoing transcatheter aortic valve implantation (TAVI). Accurate pre-operative aortic annulus measurements are crucial for patients undergoing TAVI. One hundred five patients undergoing MDCT screening before TAVI were evaluated. Aortic annular measurement was compared between automated 3mensio Valves software and manual data post-processing software on a dedicated workstation; we analyzed the discrimination value of annulus measurement for post-procedural AR in 44 recipients of a self-expanding valve. The automated 3mensio Valves software showed good concordance with manual MDCT measurements as demonstrated by Bland-Altman analysis. The automated software provided equally good reproducibility as manual measurement, especially for measurement of aortic annulus area (intraobserver intraclass correlation coefficients 0.98 vs. 0.97, interobserver 0.98 vs. 0.95). In 44 patients after implantation of a self-expanding valve, the valve diameter/CT-measured geometric mean annulus diameter ratio by automated 3mensio Valves software showed moderate and better discrimination ability in predicting post-procedural AR compared with manual measurement (p = 0.12, area under the curve 0.77, 95% confidence interval: 0.63 to 0.91, area under the curve 0.68, 95% confidence interval: 0.50 to 0.86, respectively). The automated 3mensio Valves software demonstrated reliable, reproducible aortic annulus measurement and better predictive value for post-procedural AR, suggesting important clinical implications for pre-operative assessment of patients undergoing TAVI. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights Li, Ming; Mazilu, Dumitru; Horvath, Keith A. Minimally invasive cardiac surgery is less traumatic and therefore leads to quicker recovery. With the assistance of engineering technologies on devices, imaging, and robotics, in conjunction with surgical technique, minimally invasive cardiac surgery will improve clinical outcomes and expand the cohort of patients that can be treated. We used transapical aortic valve implantation as an example to demonstrate that minimally invasive cardiac surgery can be implemented with the integration of surgical techniques and engineering technologies. Feasibility studies and long-term evaluation results prove that transapical aortic valve implantation under MRI guidance is feasible and practical. We are investigating an MRI compatible robotic surgical system to further assist the surgeon to precisely deliver aortic valve prostheses via a transapical approach. Ex vivo experimentation results indicate that a robotic system can also be employed in in vivo models. PMID:23125924 Bombien, René; Lesche, Claudia; Lozonschi, Lucian; Feucker, Max; Brinkmann, Ralf; Dahmen, Christian; Schünke, Michael; Cremer, Jochen; Lutter, Georg : The feasibility of endovascular resection of highly calcified aortic valves has already been demonstrated by our group. Different endovascular and intracardiac tractability methods were applied. In this study, these technologies were analyzed comparing the tractability, the resection time, and the lesions in the surrounding tissue. : All aortic valve resections (seven human hearts and 21 porcine hearts) were performed using a Thulium:YAG laser (continuous wave, wavelength of 2.01 μm, 20 watts power rating). In the first resection system, the laser fiber was controlled by a free in-lying flexible endoscope (Ø 2.5 mm, length of 600 mm). The distal part of the endoscope (40 mm) was moved in one plane by proximal manual control (three degrees of freedom). The resection system was separated into defined rooms assigning one room for one tool. The fiber was controlled by the above-mentioned endoscope (*) (three degrees of freedom). The third resection system was a mechanical microactuator carrying the laser fiber (three degrees of freedom). The fourth resection system contains a rotatable inlay with defined rooms and a newly designed nitinol (NiTi) microactuator that controlled the laser fiber (four degrees of freedom). The resection time per leaflet was measured in minutes. Gross anatomy and histology in the surrounding tissue were evaluated. : The resection time in approaches 1, 2, 3, and 4 was 5.5 ± 2.3 minutes, 7.4 ± 2.7 minutes, ± 6.6 minutes, and2.3 ± 1.2 minutes, respectively. The gross anatomy and histology of collateral damages revealed only superficial lesions of the surrounding tissue. The amount of lesions and the resection time were lower in the fourth approach with four degrees of freedom. : This analysis demonstrated that a precise tractability with four degrees of freedom is necessary for a faster and safer endovascular resection of the aortic valve. The analysis will help to optimize the ongoing development of the endovascular and intracardiac Atkins, Samantha K; Sucosky, Philippe The bicuspid aortic valve (BAV) is the most common form of inheritable cardiac defect. Although this abnormality may still achieve normal valvular function, it is often associated with secondary valvular and aortic complications such as calcific aortic valve disease and aortic dilation. The clinical significance and economic burden of BAV disease justify the need for improved clinical guidelines and more robust therapeutic modalities, which address the root-cause of those pathologies. Unfortunately, the etiology of BAV valvulopathy and aortopathy is still a debated issue. While the BAV anatomy and its secondary complications have been linked historically to a common genetic root, recent advances in medical imaging have demonstrated the existence of altered hemodynamics near BAV leaflets prone to calcification and BAV aortic regions vulnerable to dilation. The abnormal mechanical stresses imposed by the BAV on its leaflets and on the aortic wall could be transduced into cell-mediated processes, leading ultimately to valvular calcification and aortic medial degeneration. Despite increasing evidence for this hemodynamic etiology, the demonstration of the involvement of mechanical abnormalities in the pathogenesis of BAV disease requires the investigation of causality between the blood flow environment imposed on the leaflets and the aortic wall and the local biology, which has been lacking to date. This editorial discusses the different hypothetical etiologies of BAV disease with a particular focus on the most recent advances in cardiovascular imaging, flow characterization techniques and tissue culture methodologies that have provided new evidence in support of the hemodynamic theory. Decroly, P; Vandenbossche, J L; Englert, M We report a case of mitral valve aneurysm formation and perforation, secondary to Streptococcus sanguis endocarditis of the aortic valve. Aneurysm formation was documented by cross-sectional echocardiography and its perforation was established by Doppler colour flow mapping, and subsequently confirmed at surgery. Chiam, Paul T L; Ewe, See Hooi Transcatheter aortic valve implantation (TAVI), also known as transcatheter aortic valve replacement, is increasingly performed worldwide and is a technology that is here to stay. It has become the treatment of choice for inoperable patients and an alternative option for patients at high surgical risk with severe aortic stenosis. Early results of TAVI in intermediate-risk patients appear promising although larger randomized trial results are awaited before the widespread adoption of this technology in this big pool of patients. In patients with bicuspid aortic stenosis and degenerated surgical bioprostheses, TAVI has been shown to be feasible and relatively safe, though certain important considerations remain. Indications for TAVI are likely to grow as newer generation and improved devices and delivery systems become available. Kawase, Isamu; Ozaki, Shigeyuki; Yamashita, Hiromasa; Uchida, Shin; Nozawa, Yukinari; Matsuyama, Takayoshi; Takatoh, Mikio; Hagiwara, So This study aimed to report on original aortic valve reconstruction for patients on dialysis. Aortic valve reconstruction has been performed on 404 cases from April 2007 through September 2011. Among them, 54 cases on haemodialysis were retrospectively studied. Forty-seven patients had aortic stenosis, 5 had aortic regurgitation (AR), and 2 had infective endocarditis. Mean age was 70.2 ± 8.5 years. There were 35 males and 19 females. There were 27 primary aortic valve reconstructions, 11 with CABG, 6 with ascending aortic replacement, 5 with mitral valve repair and 4 with maze. First, in the procedure, harvested pericardium was treated with 0.6% glutaraldehyde solution. After resecting the cusps, we measured the distance between commissures with original sizing instrument. Then, the pericardium was trimmed with the original template. Three cusps were sutured to each annulus. Peak pressure gradient averaged to 66.0 ± 28.2 mmHg preoperatively, and decreased to 23.4 ± 10.7, 13.8 ± 5.5 and 13.3 ± 2.3 mmHg, 1 week, 1 year, and 3 years after the operation, respectively. No calcification was detected with echocardiographic follow-up. Recurrence of AR was not recorded with the mean follow-up of 847 days except for 1 case reoperated on for infective endocarditis 2.5 years after the operation. Three hospital deaths were recorded due to non-cardiac causes. Other patients were in good condition. There was no thromboembolic event. Medium-term results are excellent. Since warfarin for dialysis patients becomes problematic, a postoperative warfarin-free status is desirable. Aortic valve reconstruction can provide patients with a better quality of life without warfarin. Kawase, Isamu; Ozaki, Shigeyuki; Yamashita, Hiromasa; Uchida, Shin; Nozawa, Yukinari; Matsuyama, Takayoshi; Takatoh, Mikio; Hagiwara, So OBJECTIVES This study aimed to report on original aortic valve reconstruction for patients on dialysis. METHODS Aortic valve reconstruction has been performed on 404 cases from April 2007 through September 2011. Among them, 54 cases on haemodialysis were retrospectively studied. Forty-seven patients had aortic stenosis, 5 had aortic regurgitation (AR), and 2 had infective endocarditis. Mean age was 70.2 ± 8.5 years. There were 35 males and 19 females. There were 27 primary aortic valve reconstructions, 11 with CABG, 6 with ascending aortic replacement, 5 with mitral valve repair and 4 with maze. First, in the procedure, harvested pericardium was treated with 0.6% glutaraldehyde solution. After resecting the cusps, we measured the distance between commissures with original sizing instrument. Then, the pericardium was trimmed with the original template. Three cusps were sutured to each annulus. RESULTS Peak pressure gradient averaged to 66.0 ± 28.2 mmHg preoperatively, and decreased to 23.4 ± 10.7, 13.8 ± 5.5 and 13.3 ± 2.3 mmHg, 1 week, 1 year, and 3 years after the operation, respectively. No calcification was detected with echocardiographic follow-up. Recurrence of AR was not recorded with the mean follow-up of 847 days except for 1 case reoperated on for infective endocarditis 2.5 years after the operation. Three hospital deaths were recorded due to non-cardiac causes. Other patients were in good condition. There was no thromboembolic event. CONCLUSIONS Medium-term results are excellent. Since warfarin for dialysis patients becomes problematic, a postoperative warfarin-free status is desirable. Aortic valve reconstruction can provide patients with a better quality of life without warfarin. PMID:23427312 Ohno, Y; Tamburino, C; Barbanti, M Based on randomized trials with first generation devices, transcatheter aortic valve replacement (TAVI) has been included into the treatment strategy for high-risk and inoperable patients with severe aortic stenosis. Procedural complications remain a concern with TAVI, including stroke, vascular complications, paravalvular leak (PVL) and conduction disturbances. Addressing these limitations will support TAVI use in lower risk populations. This review discussed features and most recent clinical evidence of the new balloon-expandable THV (SAPIEN 3, Edwards Lifescience, Irvine, CA, USA). Webb, Rachel H; Culliford-Semmens, Nicola; Sidhu, Karishma; Wilson, Nigel J Objective We aimed to define the normal range of aortic and mitral valve thickness in healthy schoolchildren from a high prevalence rheumatic heart disease (RHD) region, using a standardised protocol for imaging and measurement. Methods Measurements were performed in 288 children without RHD. Anterior mitral valve leaflet (AMVL) thickness measurements were performed at the midpoint and tip of the leaflet in the parasternal long axis (PSLA) in diastole, when the AMVL was approximately parallel to the ventricular septum. Thickness of the aortic valve was measured from PSLA imaging in systole when the leaflets were at maximum excursion. The right coronary and non-coronary closure lines of the aortic valve were measured in diastole in parasternal short axis (PSSA) imaging. Results were compared with 51 children with RHD classified by World Heart Federation diagnostic criteria. Results In normal children, median AMVL tip thickness was 2.0 mm (IQR 1.7–2.4) and median AMVL midpoint thickness 2.0 mm (IQR 1.7–2.4). The median aortic valve thickness was 1.5 mm (IQR 1.3–1.6) in the PSLA view and 1.4 mm (IQR 1.2–1.6) in the PSSA view. The interclass correlation coefficient for the AMVL tip was 0.85 (0.71 to 0.92) and for the AMVL midpoint was 0.77 (0.54 to 0.87). Conclusions We have described a standardised method for mitral and aortic valve measurement in children which is objective and reproducible. Normal ranges of left heart valve thickness in a high prevalence RHD population are established. These results provide a reference range for school-age children in high prevalence RHD regions undergoing echocardiographic screening. PMID:28405228 Webb, John; Rodés-Cabau, Josep; Fremes, Stephen; Pibarot, Philippe; Ruel, Marc; Ibrahim, Reda; Welsh, Robert; Feindel, Christopher; Lichtenstein, Samuel Patients with severe symptomatic aortic stenosis have a poor prognosis with medical management alone, and balloon aortic valvuloplasty has failed to provide durable clinical benefit. Open surgical replacement of the aortic valve can improve symptoms and survival. Recently, transcatheter aortic valve implantation (TAVI) has been demonstrated to improve survival, quality of life, and functional status in nonoperable patients and to be a viable option for patients in whom the risk of open surgical morbidity or mortality is high. This Canadian Cardiovascular Society position statement represents the consensus of a representative group of cardiologists and cardiac surgeons as to the current, but evolving, role of this less-invasive new therapy. Specific recommendations are provided for selection of patients for TAVI vs surgical aortic valve replacement for native valves and for bioprostheses, approaches to patient evaluation for TAVI, appropriate constitution of multidisciplinary teams involved in performing TAVI, essential facilities that are needed to perform TAVI safely and effectively, and training/qualifications for TAVI operators. Cost considerations, complication rates, and the quality of the available evidence are also discussed. It is hoped that this consensus document will prove to be a useful resource for health professionals, institutions, departments, and decision-making bodies dealing with this important and rapidly evolving therapy. Szeto, Kai; Nguyen, Tran; Rodriguez, Javier; Pastuszko, Peter; Nigam, Vishal; Lasheras, Juan Previous studies have shown that congentially bicuspid aortic valves develop degenerative diseases earlier than the standard trileaflet, but the causes are not well understood. It has been hypothesized that the asymmetrical flow patterns and turbulence found in the bileaflet valves together with abnormally high levels of strain may result in an early thickening and eventually calcification and stenosis. Central to this hypothesis is the need for a precise quantification of the differences in the strain rate levels between bileaflets and trileaflet valves. We present here some in-vitro dynamic measurements of the spatial variation of the strain rate in pig aortic vales conducted in a left ventricular heart flow simulator device. We measure the strain rate of each leaflet during the whole cardiac cycle using phase-locked stereoscopic three-dimensional image surface reconstruction techniques. The bicuspid case is simulated by surgically stitching two of the leaflets in a normal valve. Baikoussis, Nikolaos G.; Argiriou, Michalis; Argiriou, Orestis; Dedeilias, Panagiotis Despite cardiovascular disease in patients with dwarfism is not rare; there is a lack of reports referring to cardiac interventions in such patients. Dwarfism may be due to achondroplasia or hormonal growth disorders. We present a 58-year-old woman with episodes of dyspnea for several months. She underwent on transthoracic echocardiography, and she diagnosed with severe aortic valve stenosis. She referred to our department for surgical treatment of this finding. In accordance of her anthropometric characteristics and her very small aortic annulus, we had the dilemma of prosthesis selection. We decided to implant a stentless valve to optimize her effective orifice area. Our aim is to present the successful Perceval S valve implantation and the descriptions of the problems coming across in operating on these special patients. To our knowledge, this is the first case patient in which a Perceval S valve is implanted according to the international bibliography. PMID:26750695 Transcatheter aortic valve implantation in patients with severe aortic valve stenosis and large aortic annulus, using the self-expanding 31-mm Medtronic CoreValve prosthesis: first clinical experience. Nijhoff, Freek; Agostoni, Pierfrancesco; Amrane, Hafid; Latib, Azeem; Testa, Luca; Oreglia, Jacopo A; De Marco, Federico; Samim, Mariam; Bedogni, Francesco; Maisano, Francesco; Bruschi, Giuseppe; Colombo, Antonio; Van Boven, Ad J; Stella, Pieter R With the introduction of the 31-mm Medtronic CoreValve prosthesis, patients with large aortic annulus have become eligible for transcatheter aortic valve implantation. The aim of this study was to evaluate the feasibility, efficacy, and safety of transcatheter aortic valve implantation using the 31-mm Medtronic CoreValve in patients with severe aortic valve stenosis and large aortic annulus. Five institutions in the Netherlands and Italy participated in a retrospective multicenter registry. Clinical, procedural, and imaging data of patients treated with the 31-mm Medtronic CoreValve were retrospectively collected in accordance with the Valve Academic Research Consortium-2 criteria. Between August 2011 and November 2012, 47 patients (44 men, mean age 77.6 ± 8.9 years) received the 31-mm Medtronic CoreValve prosthesis for severe aortic stenosis. Device success (correct positioning of a single valve with intended performance and no all-cause 30-day mortality) was achieved in 31 patients (66.0%). Reasons for failing the device success criteria were significant prosthetic aortic regurgitation in 3 patients (6.4%), second valve implantation in 10 patients (21.2%) (8 cases of malpositioning with high-grade aortic regurgitation, 1 acute valve dislocation, and 1 delayed valve dislocation), 1 of whom died intrahospital, and in-hospital mortality in a further 3 patients (6.4%). Peak and mean transaortic gradients decreased significantly (P < .01). The rate of new pacemaker implantations was 41.7%. In this retrospective multicenter registry, transcatheter treatment of severe aortic valve stenosis with the 31-mm Medtronic CoreValve seemed to be challenging, even in experienced hands. If the prosthesis is properly implanted, it offers adequate valve hemodynamics and proper functioning. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved. Bruschi, Giuseppe; Botta, Luca; De Marco, Federico; Colombo, Paola; Nonini, Sandra; Klugmann, Silvio; Martinelli, Luigi Transcatheter aortic valve implantation using the Medtronic CoreValve is a well-established procedure. Although previously carried out only through the common femoral artery, today it is possible to perform the procedure through different arterial alternative access sites. A direct aortic approach through the ascending aorta could be carried out via a right anterior mini-thoracotomy in the second intercostal space. The pericardium is opened to expose the aorta. Two purse-string sutures are then placed on the ascending aorta and a standard retrograde CoreValve implantation is performed with the standard delivery system. Advantages, contraindications, surgical technique and results are discussed. Keeble, Thomas R; Khokhar, Arif; Akhtar, Mohammed Majid; Mathur, Anthony; Weerackody, Roshan; Kennon, Simon The role of percutaneous balloon aortic valvuloplasty (BAV) in the management of severe symptomatic aortic stenosis has come under the spotlight following the development of the transcatheter aortic valve implantation (TAVI) technique. Previous indications for BAV were limited to symptom palliation and as a bridge to definitive therapy for patients undergoing conventional surgical aortic valve replacement (AVR). In the TAVI era, BAV may also be undertaken to assess the ‘therapeutic response’ of a reduction in aortic gradient in borderline patients often with multiple comorbidities, to assess symptomatic improvement prior to consideration of definitive TAVI intervention. This narrative review aims to update the reader on the current indications and practical techniques involved in undertaking a BAV procedure. In addition, a summary of the haemodynamic and clinical outcomes, as well as the frequently encountered procedural complications is presented for BAV procedures conducted during both the pre-TAVI and post-TAVI era. PMID:28008354 Keeble, Thomas R; Khokhar, Arif; Akhtar, Mohammed Majid; Mathur, Anthony; Weerackody, Roshan; Kennon, Simon The role of percutaneous balloon aortic valvuloplasty (BAV) in the management of severe symptomatic aortic stenosis has come under the spotlight following the development of the transcatheter aortic valve implantation (TAVI) technique. Previous indications for BAV were limited to symptom palliation and as a bridge to definitive therapy for patients undergoing conventional surgical aortic valve replacement (AVR). In the TAVI era, BAV may also be undertaken to assess the 'therapeutic response' of a reduction in aortic gradient in borderline patients often with multiple comorbidities, to assess symptomatic improvement prior to consideration of definitive TAVI intervention. This narrative review aims to update the reader on the current indications and practical techniques involved in undertaking a BAV procedure. In addition, a summary of the haemodynamic and clinical outcomes, as well as the frequently encountered procedural complications is presented for BAV procedures conducted during both the pre-TAVI and post-TAVI era. Benedik, Jaroslav; Pilarczyk, Kevin; Wendt, Daniel; Indruch, Jiri; Flek, Radek; Tsagakis, Konstantinos; Alaeddine, Savvas; Jakob, Heinz Objectives. Bicuspid aortic valve (AV) represents the most common form of congenital AV malformation, which is frequently associated with pathologies of the ascending aorta. We compared the mechanical properties of the aortic wall between patients with bicuspid and tricuspid AV using a new custom-made device mimicking transversal aortic wall shear stress. Methods. Between 03/2010 and 07/2011, 190 consecutive patients undergoing open aortic valve replacement at our institution were prospectively enrolled, presenting either with a bicuspid (group 1, n = 44) or a tricuspid (group 2, n = 146) AV. Aortic wall specimen were examined with the "dissectometer" resulting in nine specific aortic-wall parameters derived from tensile strength curves (TSC). Results. Patients with a bicuspid AV showed significantly more calcified valves (43.2% versus 15.8%, P < 0.001), and a significantly thinner aortic wall (2.04 ± 0.42 mm versus 2.24 ± 0.41 mm, P = 0.008). Transesophageal echocardiography diameters (annulus, aortic sinuses, and sinotubular junction) were significantly larger in the bicuspid group (P = 0.003, P = 0.02, P = 0.01). We found no difference in the aortic wall cohesion between both groups as revealed by shear stress testing (P = 0.72, P = 0.40, P = 0.41). Conclusion. We observed no differences of TSC in patients presenting with tricuspid or bicuspid AVs. These results may allow us to assume that the morphology of the AV and the pathology of the ascending aorta are independent. Guyton, Robert A; Block, Peter C; Thourani, Vinod H; Lerakis, Stamatios; Babaliaros, Vasilis We report three patients who had successful transcatheter aortic valve replacement (TAVR) via carotid artery access. None were candidates for thoracotomy (including minimal access incisions) and had no other vascular access sites that would accommodate the transcatheter valve sheath. Antegrade carotid perfusion and retrograde insertion of the delivery sheath maintained cerebral blood flow without sequelae. Carotid access for TAVR is an option for unusual patients without other access. Rodriguez-Ospina, Luis; Garcia-Morell, Juan; Rodriguez-Monserrate, Carla P; Valentin-Nieves, Julio Valve replacement is the standard surgical treatment of diseased valves that cannot be repaired. The main goal of replacement is to exchange the diseased valve with one that has the engineering and hemodynamics as close as possible to the disease free native valve. However due to mechanical and fluid dynamic constraints all prosthetic heart valves (PHVs) are smaller than normal and thus are inherently stenotic. This represents a challenge when it comes time to replace a valve. The correct valve with the correct and matching profile has to be selected before the procedure to avoid possible complications. It is well recognized that patients are also prone to patient-prosthesis mismatch at long term which could have consequences in the clinical outcomes (1). The evaluation of patient-prosthesis mismatch (PPM) has not been sufficiently emphasized in common practice. Failure to recognize this fact may lead to significant hemodynamic impairment and worsening of the clinical status over the time. Making efforts to identifying patients at risk may decrease the prevalence of PPM, the economic impact to our health system, the morbidity and mortality involved in these cases as well as creates efforts to standardized pre-operative protocols to minimized risk of PPM. We present a case of a 78 years old male patient who underwent aortic valve replacement due severe aortic stenosis, afterwards his clinical course got complicated with several admissions for shortness of breath and decompensated congestive heart failure (CHF). Simard, Louis; Côté, Nancy; Dagenais, François; Mathieu, Patrick; Couture, Christian; Trahan, Sylvain; Bossé, Yohan; Mohammadi, Siamak; Pagé, Sylvain; Joubert, Philippe; Clavel, Marie-Annick Calcific aortic stenosis (AS) is characterized by calcium deposition in valve leaflets. However, women present lower aortic valve calcification loads than men for the same AS hemodynamic severity. We, thus, aimed to assess sex differences in aortic valve fibrocalcific remodeling. One hundred and twenty-five patients underwent Doppler echocardiography and multidetector computed tomography within 3 months before aortic valve replacement. Explanted stenotic tricuspid aortic valves were weighed, and fibrosis degree was determined. Sixty-four men and 39 women were frequency matched for age, body mass index, hypertension, renal disease, diabetes mellitus, and AS severity. Mean age (75±9 years), mean gradient (41±18 mm Hg), and indexed aortic valve area (0.41±0.12 cm(2)/m(2)) were similar between men and women (all P≥0.18). Median aortic valve calcification (1973 [1124-3490] Agatston units) and mean valve weight (2.36±0.99 g) were lower in women compared with men (both P<0.0001). Aortic valve calcification density correlated better with valve weight in men (r(2)=0.57; P<0.0001) than in women (r(2)=0.26; P=0.0008). After adjustment for age, body mass index, aortic valve calcification density, and aortic annulus diameter, female sex was an independent risk factor for higher fibrosis score in AS valves (P=0.003). Picrosirius red staining of explanted valves showed greater amount of collagen fibers (P=0.01), and Masson trichrome staining revealed a greater proportion of dense connective tissue (P=0.02) in women compared with men. In this series of patients with tricuspid aortic valve and similar AS severity, women have less valvular calcification but more fibrosis compared with men. These findings suggest that the pathophysiology of AS and thus potential targets for drug development may be different according to sex. © 2016 American Heart Association, Inc. Chiu, Peter; Fearon, William F; Raleigh, Lindsay A; Burdon, Grayson; Rao, Vidya; Boyd, Jack H; Yeung, Alan C; Miller, David Craig; Fischbein, Michael P We describe a patient who presented in profound cardiogenic shock due to bioprosthetic aortic valve stenosis requiring salvage Extracorporeal Membrane Oxygenation followed by a "bridge" valve-in-valve transcatheter aortic valve replacement. doi: 10.1111/jocs.12750 (J Card Surg 2016;31:403-405). Johansen, Peter; Travis, Brandon R; Smerup, Morten; Decker Christensen, Thomas; Funder, Jonas; Nyboe, Camilla; Nygaard, Hans; Hasenkam, J Michael When implanting a mechanical aortic valve the annulus orientation is important with respect to turbulence. However, the effect on cavitation has not yet been investigated. The aim of this study was to investigate how cavitation is influenced hereof in vivo. Three pigs were included in the study. An Omnicarbon 21mm valve equipped with a rotating mechanism enabling controlled rotation of the valve was implanted in aortic position. Under stable hemodynamic conditions, measurements were performed using a hydrophone positioned at the aortic root. The valve was rotated from 0-360° in increments of 30°. From the pressure fluctuations recorded by the hydrophone the root mean square of the 50 kHz high pass filtered signal as well as the non-deterministic signal energy was calculated as indirect measures of cavitation. Various degrees of cavitation were measured but no relationship was found between either of the two cavitation measures and the valve orientation. Hemodynamics varied during the experiments for all pigs (3.9-5.7 l/min; 5.0-7.2 l/min; 3.1-7.5 l/min). Changes in cavitation quantities seemed to be caused by changes in hemodynamics rather than valve angular position. In conclusion, these results do not favor any position over another in terms of cavitation potential. Nicolini, Francesco; Beghi, Cesare; Gherli, Tiziano The KBG syndrome is a very rare condition characterized by developmental delay, short stature, distinct facial dysmorphism, macrodontia of the upper central incisors and skeletal abnormalities. Associated congenital heart defects have been described in 9% of patients. Herein is described a case of aortic root dilatation with significant regurgitation in a young patient affected by KBG syndrome. Surgical inspection showed a dilated aortic annulus, slightly dilated aortic sinuses, a tricuspid valvb with slightly thickened cuspal margins and central regurgitation. Histological examination showed a fibrous hyaline involution of the valvular leaflets. To the authors' knowledge, this is the first reported case of KBG syndrome affected by aortic root dilatation with severe regurgitation. Morphology of the aortic valve leaflets was relatively normal, but the annulus was dilated in the absence of any history of rheumatic fever, hypertension, connective tissue or rheumatic systemic diseases. The unusual findings in this young patient raised questions regarding the as-yet unexplained etiopathogenesis of the KBG syndrome. Hashmi, Maria; Dar, Mudasser Iqbal; Khan, Asad Ullah; Khan, Farhan; Khan, Abdul Bari A case of Debakey type-II (Stanford type-A) dissecting aortic aneurysm, after aortic valve replacement and reduction aortoplasty, is reported. The patient was 35 years male who was diagnosed of severe aortic regurgitation along with aortic root dilatation of 7 cm. He underwent aortic valve replacement with 27-ASt Jude's mechanical aortic valve along with reduction aortoplasty. Nine months later, he was admitted to our hospital with complaint of severe sudden anterior chest pain. Computed tomography with aortic enhancement showed dilatation and dissection of ascending aorta. Successful operation of aortic root replacement with composite graft was performed and patient was discharged without any postoperative complication. The aortic diameter at the time of aortic valve replacement is an independent risk factor for the late aortic dissection. Dolmatova, Elena; Moazzami, Kasra; Cocke, Thomas P; Elmann, Elie; Vaidya, Pranay; Ng, Arthur F; Satya, Kumar; Narayan, Rajeev L Background Patients undergoing transcatheter aortic valve replacement can experience severe perioperative complications leading to hemodynamic instability and death. Venoarterial extracorporeal membrane oxygenation can be used to provide cardiorespiratory support during this time. Methods From 2012 to 2015, of 247 patients who underwent transcatheter aortic valve replacement, 6 (2.42%) required extracorporeal membrane oxygenation support. Their mean age was 82 ± 7.4 years, mean Society of Thoracic Surgeons score was 9.4 ± 6.6, and mean aortic gradient was 28.3 ± 12 mm Hg. Rescue extracorporeal membrane oxygenation was required for hemodynamic instability due to ventricular fibrillation ( n = 1), respiratory failure ( n = 1), left ventricular wall rupture ( n = 2), and aortic annulus rupture ( n = 1). In one patient, prophylactic extracorporeal membrane oxygenation was required due to advanced heart failure. Additional procedures included valve-in-valve implantation ( n = 1), conversion to an open procedure ( n = 3), and intraaortic balloon pump insertion ( n = 1). Results The median hospital stay was 20 days. There were 2 hospital deaths in patients whose hospital course was complicated by left ventricular wall rupture or aortic annulus rupture with resulting tamponade. Among the 4 survivors, one required continuous ventilator support following discharge, and 3 experienced no major complications during the first month after discharge. Conclusions Extracorporeal membrane oxygenation can be considered a viable option for high-risk patients undergoing transcatheter aortic valve replacement and those who develop cardiac complications following this procedure and require cardiorespiratory support. Takahara, Shingo; Fukasawa, Manabu; Kawahara, Yu; Suzuki, Kotaro; Kobayashi, Yuriko Congenital bicuspid aortic valve (BAV) is one of the most common congenital heart diseases, with a high incidence of associated valvular lesions and aortic abnormalities including aortic stenosis( AS), aortic regurgitation, aortic dilatation, and aortic dissection. Patients with BAV and AS often have a small aortic annulus. We encountered a case of BAV in which a 51-year-old woman with severe AS having a small aortic annulus and a dilated ascending aorta required surgical intervention. We performed the surgery using new technique that involved concomitant replacement of the aortic valve and the ascending aorta with enlargement of the aortic annulus using a single uniquely-shaped graft to avoid prosthesis patient mismatch. We trimmed the proximal end of the straight graft in shape of 2 teardrops hanging on it to fit the cut annulus. It requires only a single suture line to replace the ascending aorta and enlarge the aortic annulus, which entails a decreased risk of bleeding during surgery. We believe that it could be applicable to many cases requiring concomitant surgery. Ranga, Adrian; Bouchot, Olivier; Mongrain, Rosaire; Ugolini, Patricia; Cartier, Raymond The goal of this study has been to develop a numerical model of the aortic valve, to validate it with in-vivo data and to computationally evaluate the effect of two types of aortic valve-sparing reconstructions on valve dynamics and hemodynamics. A model of the native aortic valve and two models of the valve after surgical reconstruction (reimplantation with a straight conduit and remodeling with a shaped conduit) were created. These models were transferred to a finite element analysis software where the interaction between valve structures and blood was taken into account in a dynamic manner. Leaflet and blood dynamics, as well as tissue compliance and stresses were evaluated. Leaflet dynamics and blood velocities were also assessed by magnetic resonance imaging in 15 healthy volunteers. Computational results in the native valve model correlated closely with the in-vivo imaging data. The creation of neo-sinuses was shown to restore leaflet opening and closing dynamics. Loss of compliance at the commissures led to altered stress distribution patterns. Preservation of sinus geometry was an important factor in end systolic vortex formation. This is the first study to have incorporated the effect of blood flow in the numerical evaluation of aortic reconstructions using a computational model validated by in-vivo data. Differences in valve dynamics after surgical reconstruction reported in this computational study match trends previously reported in other in-vivo studies. Numerical models such as this one can serve as increasingly sophisticated tools in the study of aortic valve pathologies and in the optimization of new surgical reconstruction techniques. Isoda, Susumu; Osako, Motohiko; Kimura, Tamizo; Nishimura, Kenji; Yamanaka, Nozomu; Nakamura, Shingo; Maehara, Tadaaki A 62-year-old man was referred for an aortic-valve surgery because of severe aortic stenosis. Thirty years ago, he had undergone a mitral valve commissurotomy and after 9 years, the valve had been replaced by a mechanical valve. He had been undergoing hemodialysis for the past 8 years. A computed tomographic (CT) scan of the chest and abdomen showed a dense circumferential calcification in the wall of the entire thoracic and abdominal aorta, pulmonary artery, and left and right atrium. A conventional aortic-valve replacement was performed. To avoid an embolic event, a "stepwise aortic clamp" procedure was attempted and involved the following: (1) brief circulatory arrest and aortotomy during moderate hypothermia; (2) balloon occlusion at the ascending aorta during low-flow cardiopulmonary bypass (CPB); (3) endoarterectomy by using an ultrasonic surgical aspirator to enable aortic cross-clamping; and (4) a cross-clamp reinforced with felt and full-flow CPB. The patient recovered without any thromboembolic events. Using this procedure to treat a porcelain aorta seemed to reduce the time limit and reduced the risk of brain injury during cardiac surgery. Background Culture-negative endocarditis due to Tropheryma whipplei is a rare disease. Mostly the diagnosis is made by histologic examination of resected heart valve tissue. Case presentation In this case report, we described a patient with a classical Whipple’s disease. Transesophageal echocardiography (TEE) showed a vegetation on noncoronary cusp of the aortic valve. Whipple’s disease was confirmed by positive Tropheryma whipplei polymerase chain reaction (PCR) in EDTA blood and a duodenal biopsy with positive periodic acid-Schiff stain (PAS) macrophages. Conclusion Due to timely diagnosis, our patient was treated with antibiotics without valve replacement. PMID:23110725 Hammer, Peter E.; del Nido, Pedro J. Surgical repair of the aortic valve using leaflet grafts made from pericardium has been shown to be a viable option, particularly in children, in whom valve replacement has strong disadvantages. We present guidelines for sizing treated autologous pericardium to fabricate a leaflet graft for single leaflet replacement. Both our clinical experience and experimental evidence indicate that effective repairs are best achieved using a semicircular graft with diameter 10–15% greater than the sinotubular junction diameter in diastole. We also provide a simple formula to allow adjusting these guidelines to account for variation in valve geometry and tissue properties. PMID:23816114 Izzat, Mohammad Bashar Based on the natural mathematical relationships between the components of the human tri-leaflet aortic valve, new calibrated cusp sizers were developed in order to facilitate aortic valve assessment in the operating room and enhance the chance for a perfect restoration of aortic valve competence. These sizers were used clinically to guide the implementation of established aortic valve repair techniques in 10 consecutive patients with severe aortic valve regurgitation. Valve repair was successful in all cases, and at a median follow-up was 5.5 months, aortic valve function remained stable, with aortic regurgitation ≤1+ in every patient and no significant gradient across the aortic valves. This preliminary clinical experience indicates that the calibrated cusp sizers can provide reliable insight into the mechanism of aortic valve insufficiency, and can guide aortic valve repair techniques successfully. We hope that the simplicity and reproducibility of this method would assist in its dissemination and further increase the percentage of aortic valves that are repaired when compared with current practice. PMID:22159260 Hammer, Peter E.; Chen, Peter C.; del Nido, Pedro J.; Howe, Robert D. Aortic valve reconstruction using leaflet grafts made from autologous pericardium is an effective surgical treatment for some forms of aortic regurgitation. Despite favorable outcomes in the hands of skilled surgeons, the procedure is underutilized because of the difficulty of sizing grafts to effectively seal with the native leaflets. Difficulty is largely due to the complex geometry and function of the valve and the lower distensibility of the graft material relative to native leaflet tissue. We used a structural finite element model to explore how a pericardial leaflet graft of various sizes interacts with two native leaflets when the valve is closed and loaded. Native leaflets and pericardium are described by anisotropic, hyperelastic constitutive laws, and we model all three leaflets explicitly and resolve leaflet contact in order to simulate repair strategies that are asymmetrical with respect to valve geometry and leaflet properties. We ran simulations with pericardial leaflet grafts of various widths (increase of 0%, 7%, 14%, 21% and 27%) and heights (increase of 0%, 13%, 27% and 40%) relative to the native leaflets. Effectiveness of valve closure was quantified based on the overlap between coapting leaflets. Results showed that graft width and height must both be increased to achieve proper valve closure, and that a graft 21% wider and 27% higher than the native leaflet creates a seal similar to a valve with three normal leaflets. Experimental validation in excised porcine aortas (n=9) corroborates the results of simulations. PMID:22341628 López-García, Alejandro; Carmen Fernández, M; Durán, Ana Carmen; Sans-Coma, Valentín; Fernández, Borja Occurrence of quadricuspid aortic valves has been reported in humans, in nine dogs and in a greater white-toothed shrew. Moreover, two cases of developing aortic valves with four anticipated leaflets have been described in Syrian hamster embryos. Currently, however, no case of quadricuspid aortic valve in adult hamsters has been recorded. The aim here is to present four adults of this rodent species, two of them with unequivocally quadricuspid aortic valves and the other two with quadricuspid-like aortic valves. The four anomalous aortic valves were detected among 4,190 Syrian hamsters examined in our laboratory, representing an incidence of 0.09%. None of the affected hamsters showed apparent signs of disease. The present findings are considered on the light of current empirical knowledge about the morphogenesis of quadricuspid and bicuspid aortic and pulmonary valves. Quadricuspid aortic valves result from the partition of one of the normal mesenchymal cushions which normally give rise to normal (tricuspid) valves, while quadricuspid-like valves might be the product of a combined mechanism of fusion and partition of the cushions at the onset of the valvulogenesis. The presence of aortic valves with four leaflets in ancient mammalian lineages such as insectivors and rodents suggest that quadricuspid aortic valves, although showing almost certainly a low incidence, may be widespread among the different groups of mammals, including domestic animals. Chapman, J H; Menapace, F J; Howell, R R A case of traumatic rupture of the aortic valve as a complication of the Heimlich maneuver is presented. Conformation was made by comparative echocardiographic studies available from three months before and immediately following the incident. The patient refused surgical intervention and died one month later with severe congestive heart failure despite vigorous medical therapy. Chandra, Santanu; Seaman, Clara; Sucosky, Philippe The bicuspid aortic valve (BAV) is a congenital defect in which the aortic valve forms with two leaflets instead of three. While calcific aortic valve disease (CAVD) also develops in the normal tricuspid aortic valve (TAV), its progression in the BAV is more rapid. Although studies have suggested a mechano-potential root for the disease, the native BAV hemodynamics remains largely unknown. This study aimed at characterizing BAV hemodynamics and quantifying the degree of wall-shear stress (WSS) abnormality on BAV leaflets. Fluid-structure interaction models validated with particle-image velocimetry were designed to predict the flow and leaflet dynamics in idealized TAV and BAV anatomies. Valvular function was quantified in terms of the effective orifice area. The regional leaflet WSS was characterized in terms of oscillatory shear index, temporal shear magnitude and temporal shear gradient. The predictions indicate the intrinsic degree of stenosis of the BAV anatomy, reveal drastic differences in shear stress magnitude and pulsatility on BAV and TAV leaflets and confirm the side- and site-specificity of the leaflet WSS. Given the ability of abnormal fluid shear stress to trigger valvular inflammation, these results support the existence of a mechano-etiology of CAVD in the BAV. Guérios, Enio E; Wenaweser, Peter; Meier, Bernhard Previous reports prove the safety and efficacy of cardiac pacing employing a guidewire in the left ventricle as unipolar pacing electrode. We describe the use of left ventricular guidewire pacing as an alternative to conventional transvenous temporary right ventricular pacing in the context of transcatheter aortic valve implantation. Freeman, Melanie; Barbanti, Marco; Wood, David A; Ye, Jian; Webb, John G Stroke has emerged as one of the most concerning complications following transcatheter aortic valve replacement (TAVR), associated with high morbidity and mortality. We discuss the potential mechanisms of stroke following TAVR, as well as the newly developed embolic protection devices aimed to reduce the risk of stroke. Schoenhagen, Paul; Kapadia, Samir R; Halliburton, Sandra S; Svensson, Lars G; Tuzcu, E Murat For patients with severe aortic stenosis, open-heart surgical valve replacement remains the current clinical standard with documented, excellent long-term outcome. Over the past few years, transcatheter aortic valve implantation (TAVI) has developed into a treatment alternative for high-risk patients with severe aortic stenosis. Because transcatheter valvular procedures are characterized by lack of exposure of the operative field, image guidance is critical. This Pictorial Essay describes the role of 3-dimensional imaging with multidetector row computed tomography for detailed reconstructions of the aortic valve, aortic root, and iliac arteries in the context of TAVI. Itagaki, Shinobu; Chiang, Yuting; Tang, Gilbert H L The bicuspid aortic valve (BAV) is, by far, the most common congenital cardiovascular defect encountered by cardiovascular specialists. In the United States, the number of subjects alive is estimated to be 3 million, with an approximate 1% prevalence, more than 10 times higher than the second most common congenital lesion, ventricular septal defect. BAV is subjected to early degeneration and valve dysfunction, requiring surgical intervention in the course of a lifetime for most patients. BAV is also associated with ascending aortic dilatation, also known as BAV aortopathy. Surgical indications for a dysfunctional BAV are relatively straightforward and well established; the same as those for tricuspid aortic valve (TAV), usually triggered by symptoms or ventricular dysfunction. On the other hand, while sharing the same ultimate goal of preventing life-threatening consequences, such as aortic dissection and rupture, surgical thresholds for a dilated ascending aorta are different in the setting of BAV versus TAV; generally lower in BAV. Recently, the incidence of aortic dissection was reported to be much lower than believed, and the idea of more aggressive preemptive intervention on BAV aortopathy has become controversial. Instead, the importance of a more individualized approach is being highlighted. This article will provide a comprehensive review of (1) the typical clinical course of patients with BAV under contemporary management, (2) new risk-stratifying parameters proposed to make an individualized approach possible, and (3) practical challenges all cardiovascular specialists need to know when implementing and interpreting future BAV-related studies. Park, Sang Min; Jeong, Haemin; Hong, Kyung-Soon; Kim, Christopher Abstract Background: In a patient underwent aortic valve replacement (AVR) due to bicuspid aortic valve (BAV) insufficiency without marked dilation of ascending aorta, the development of delayed-typed aneurysmal complication of ascending aorta has been often reported because the dilated aorta tends to grow insidiously with age. Case summary: A 58-year-old man who underwent AVR with mechanical valve due to severe aortic regurgitation secondary to BAV 7 years previously presented with exertional chest discomfort for 1 year. An echocardiography showed a well-functioning mechanical aortic valve without any significant abnormal findings. Cardiac multidetector computed tomography (MDCT) revealed a huge saccular aortic root aneurysm (79.7 mm × 72.8 mm in size) compressing the proximal right coronary artery resulting in ∼90% eccentric diffuse luminal narrowing. The patient subsequently underwent open-heart surgery with resection of the ascending aortic aneurysmal sac and consecutive ascending aorta and hemi-arch replacement using a graft. Conclusion: After successful AVR in the patient with BAV insufficiency and mildly dilated ascending aorta, a regular aortic imaging such as cardiac MDCT with aortography would be helpful to monitor the morphology and size of ascending aorta and related complications to guide future management. PMID:27749539 Freeze, Samantha L; Landis, Benjamin J; Ware, Stephanie M; Helm, Benjamin M Bicuspid aortic valve (BAV) is the most common congenital heart defect and falls in the spectrum of left-sided heart defects, also known as left ventricular outflow tract obstructive (LVOTO) defects. BAV is often identified in otherwise healthy, asymptomatic individuals, but it is associated with serious long term health risks including progressive aortic valve disease (stenosis or regurgitation) and thoracic aortic aneurysm and dissection. BAV and other LVOTO defects have high heritability. Although recommendations for cardiac screening of BAV in at-risk relatives exist, there are no standard guidelines for providing genetic counseling to patients and families with BAV. This review describes current knowledge of BAV and associated aortopathy and provides guidance to genetic counselors involved in the care of patients and families with these malformations. The heritability of BAV and recommendations for screening are highlighted. While this review focuses specifically on BAV, the principles are applicable to counseling needs for other LVOTO defects. Freeze, Samantha L.; Ware, Stephanie M.; Helm, Benjamin M. Bicuspid aortic valve (BAV) is the most common congenital heart defect and falls in the spectrum of left-sided heart defects, also known as left ventricular outflow tract obstructive (LVOTO) defects. BAV is often identified in otherwise healthy, asymptomatic individuals, but it is associated with serious long term health risks including progressive aortic valve disease (stenosis or regurgitation) and thoracic aortic aneurysm and dissection. BAV and other LVOTO defects have high heritability. Although recommendations for cardiac screening of BAV in at-risk relatives exist, there are no standard guidelines for providing genetic counseling to patients and families with BAV. This review describes current knowledge of BAV and associated aortopathy and provides guidance to genetic counselors involved in the care of patients and families with these malformations. The heritability of BAV and recommendations for screening are highlighted. While this review focuses specifically on BAV, the principles are applicable to counseling needs for other LVOTO defects. PMID:27550231 Ramlawi, Basel; Anaya-Ayala, Javier E; Reardon, Michael J Transcatheter aortic valve replacement (TAVR) has proven to be a viable tool for the high-surgical-risk population with severe aortic valve stenosis. Vascular access complications are not uncommon with TAVR and may increase early and late mortality. Avoiding these serious complications is the goal. With experience and careful screening, we are now able to risk-stratify patients who may be at increased risk of vascular complications. While the traditional iliofemoral access site remains the most common for TAVR, alternate access sites that have proven to be viable and safe alternatives include the transapical, direct-aortic, and subclavian techniques. TAVR teams should be familiar and comfortable with these approaches as each of them has its own advantages and weaknesses. The best option is usually one in which the procedure is tailored to the patient. The present review examines our current access planning and strategies for TAVR. Fernández Esmerats, Joan; Heath, Jack; Jo, Hanjoong Currently, calcific aortic valve disease (CAVD) is only treatable through surgical intervention because the specific mechanisms leading to the disease remain unclear. In this review, we explore the forces and structure of the valve, as well as the mechanosensors and downstream signaling in the valve endothelium known to contribute to inflammation and valve dysfunction. While the valvular structure enables adaptation to dynamic hemodynamic forces, these are impaired during CAVD, resulting in pathological systemic changes. Mechanosensing mechanisms-proteins, sugars, and membrane structures-at the surface of the valve endothelial cell relay mechanical signals to the nucleus. As a result, a large number of mechanosensitive genes are transcribed to alter cellular phenotype and, ultimately, induce inflammation and CAVD. Transforming growth factor-β signaling and Wnt/β-catenin have been widely studied in this context. Importantly, NADPH oxidase and reactive oxygen species/reactive nitrogen species signaling has increasingly been recognized to play a key role in the cellular response to mechanical stimuli. In addition, a number of valvular microRNAs are mechanosensitive and may regulate the progression of CAVD. While numerous pathways have been described in the pathology of CAVD, no treatment options are available to avoid surgery for advanced stenosis and calcification of the aortic valve. More work must be focused on this issue to lead to successful therapies for the disease. Ultimately, a more complete understanding of the mechanisms within the aortic valve endothelium will lead us to future therapies important for treatment of CAVD without the risks involved with valve replacement or repair. Antioxid. Redox Signal. 25, 401-414. Wirrig, Elaine E.; Gomez, M. Victoria; Hinton, Robert B.; Yutzey, Katherine E. Objective Calcific aortic valve disease (CAVD) is a significant cause of morbidity and mortality, which affects approximately 1% of the US population and is characterized by calcific nodule formation and stenosis of the valve. Klotho-deficient mice were used to study the molecular mechanisms of CAVD as they develop robust aortic valve (AoV) calcification. Through microarray analysis of AoV tissues from klotho-deficient and wild type mice, increased expression of the gene encoding cyclooxygenase 2/COX2 (Ptgs2) was found. COX2 activity contributes to bone differentiation and homeostasis, thus the contribution of COX2 activity to AoV calcification was assessed. Approach and Results In klotho-deficient mice, COX2 expression is increased throughout regions of valve calcification and is induced in the valvular interstitial cells (VICs) prior to calcification formation. Similarly, COX2 expression is increased in human diseased AoVs. Treatment of cultured porcine aortic VICs with osteogenic media induces bone marker gene expression and calcification in vitro, which is blocked by inhibition of COX2 activity. In vivo, genetic loss of function of COX2 cyclooxygenase activity partially rescues AoV calcification in klotho-deficient mice. Moreover, pharmacologic inhibition of COX2 activity in klotho-deficient mice via celecoxib-containing diet reduces AoV calcification and blocks osteogenic gene expression. Conclusions COX2 expression is upregulated in CAVD and its activity contributes to osteogenic gene induction and valve calcification in vitro and in vivo. PMID:25722432 Korteland, Nelleke M; Bras, Frans J; van Hout, Fabienne M A; Kluin, Jolanda; Klautz, Robert J M; Bogers, Ad J J C; Takkenberg, Johanna J M Objective Current clinical practice guidelines advocate shared decision-making (SDM) in prosthetic valve selection. This study assesses among adult patients accepted for aortic valve replacement (AVR): (1) experience with current clinical decision-making regarding prosthetic valve selection, (2) preferences for SDM and risk presentation and (3) prosthetic valve knowledge and numeracy. Methods In a prospective multicentre cohort study, AVR patients were surveyed preoperatively and 3 months postoperatively. Results 132 patients (89 males/43 females; mean age 67 years (range 23–86)) responded preoperatively. Decisional conflict was observed in 56% of patients, and in 25% to such an extent that it made them feel unsure about the decision. 68% wanted to be involved in decision-making, whereas 53% agreed that they actually were. 69% were able to answer three basic knowledge questions concerning prosthetic valves correctly. 56% were able to answer three basic numeracy questions correctly. Three months postsurgery, 90% (n=110) were satisfied with their aortic valve prosthesis, with no difference between mechanical and bioprosthetic valve recipients. Conclusions In current clinical practice, many AVR patients experience decisional conflict and suboptimal involvement in prosthetic valve selection, and exhibit impaired knowledge concerning prosthetic valves and numeracy. Given the broad support for SDM among AVR patients and the obvious need for understandable information, to-be-developed tools to support SDM in the setting of prosthetic valve selection will help to improve quality of decision-making, better inform and actively involve patients, and reduce decisional conflict. Trial registration number NTR3618. PMID:25893105 Ferrari, Enrico; Franciosi, Giorgio; Clivio, Sara; Faletra, Francesco; Moccetti, Marco; Moccetti, Tiziano; Pedrazzini, Giovanni; Demertzis, Stefanos The goal was to show the technical details, feasibility and clinical results of balloon-expandable stent valve implantation in the aortic position during conventional redo open-heart surgery in selected obese patients with a small aortic prosthesis and severe patient-prosthesis mismatch. Two symptomatic overweight patients (body mass index of 31 and 38), each with a small aortic prosthesis (a 4-year-old, 21-mm Hancock II biological valve and a 29-year-old, 23-mm Duromedic mechanical valve), increased transvalvular gradients (59/31 and 74/44 mmHg) and a reduced indexed effective orifice area (0.50 and 0.43 cm 2 /m 2 ) underwent implantation of two 26-mm balloon-expandable Sapien 3 valves during standard on-pump redo valve surgery. Using full re-sternotomy, cardiopulmonary bypass and cardioplegic arrest, the two balloon-expandable stent valves were implanted under direct view using a standard aortotomy, after prosthesis removal and without annulus enlargement. Aortic cross-clamp times were 162 and 126 min; cardiopulmonary bypass times were 178 and 180 min; total surgical times were 360 and 318 min. At discharge, echocardiograms showed transvalvular peak and mean gradients of 13/9 and 23/13 mmHg and indexed effective orifice areas of 0.64 and 1.08 cm 2 /m 2 . The 3-month echocardiographic follow-up showed transvalvular peak and mean gradients of 18/9 and 19/11 mmHg and indexed effective orifice areas of 0.78 cm 2 /m 2 and 0.84 cm 2 /m 2 , with improved symptoms (New York Heart Association class 1). Implantation of a balloon-expandable stent valve during redo aortic valve surgery is feasible in selected cases and prevents patient-prosthesis mismatch in obese patients without need for aortic annulus enlargement. Moreover, in the case of stent valve degeneration, this approach permits additional valve-in-valve procedures with large stent valves and prevents re-redo surgery. Abedat, Suzan; Beeri, Ronen; Valitsky, Michael; Daher, Sameh; Kott-Gutkowski, Miriam; Gal-Moscovici, Anca; Sosna, Jacob; Rajamannan, Nalini M.; Lotan, Chaim Renal failure is associated with aortic valve calcification. Using our rat model of uremia-induced reversible aortic valve calcification, we assessed the role of apoptosis and survival pathways in that disease. We also explored the effects of raloxifene, an estrogen receptor modulator, on valvular calcification. Gene array analysis was performed in aortic valves obtained from three groups of rats (n = 7 rats/group): calcified valves obtained from rats fed with uremic diet, valves after calcification resolution following diet cessation, and control. In addition, four groups of rats (n = 10 rats/group) were used to evaluate the effect of raloxifene in aortic valve calcification: three groups as mentioned above and a fourth group fed with the uremic diet that also received daily raloxifene. Evaluation included imaging, histology, and antigen expression analysis. Gene array results showed that the majority of the altered expressed genes were in diet group valves. Most apoptosis-related genes were changed in a proapoptotic direction in calcified valves. Apoptosis and decreases in several survival pathways were confirmed in calcified valves. Resolution of aortic valve calcification was accompanied by decreased apoptosis and upregulation of survival pathways. Imaging and histology demonstrated that raloxifene significantly decreased aortic valve calcification. In conclusion, downregulation of several survival pathways and apoptosis are involved in the pathogenesis of aortic valve calcification. The beneficial effect of raloxifene in valve calcification is related to apoptosis modulation. This novel observation is important for developing remedies for aortic valve calcification in patients with renal failure. PMID:21335463 Pirundini, Paul A; Balaguer, Jorge M; Lilly, Kevin J; Gorsuch, William Brian; Taft, Margaret Byrne; Cohn, Lawrence H; Rizzo, Robert J Quadricuspid aortic valves are rarely encountered by the cardiac surgeon during aortic valve replacement. The most common location for the supranumerary cusp is between the noncoronary and the right coronary cusp, located over the membranous septum, which can potentially increase the risk of complete heart block after valve replacement. We present three quadricuspid aortic valve replacements, one of which was complicated by complete heart block postoperatively. We suggest a strategy to possibly avoid this complication. Rampat, Rajiv; Khawaja, M Zeeshan; Byrne, Jonathan; MacCarthy, Philip; Blackman, Daniel J; Krishnamurthy, Arvindra; Gunarathne, Ashan; Kovac, Jan; Banning, Adrian; Kharbanda, Raj; Firoozi, Sami; Brecker, Stephen; Redwood, Simon; Bapat, Vinayak; Mullen, Michael; Aggarwal, Suneil; Manoharan, Ganesh; Spence, Mark S; Khogali, Saib; Dooley, Maureen; Cockburn, James; de Belder, Adam; Trivedi, Uday; Hildick-Smith, David This study sought to present the U.K. experience to date with the second-generation LOTUS bioprosthesis (Boston Scientific, Natick, Massachusetts). First-generation transcatheter aortic valves have limitations. Second-generation repositionable valves may improve on some of those limitations. Prospectively collected data relating to procedural and in-hospital outcome was analyzed from 10 implantation centers in the United Kingdom. Implants in 228 patients age 81.4 ± 7.6 years were studied; 53.5% were male. Mean logistic EuroScore was 17.5 ± 12.4. One hundred eighty-seven (82.0%) were undertaken for aortic stenosis, 7 (3.1%) for aortic regurgitation, and 34 (14.9%) for mixed aortic valve disease. A total of 67.1% of cases were done under local anesthetic and/or sedation with transfemoral access in 94.7% and transaortic in 5.3%. Three device sizes were used: 23 mm (n = 66, 28.9%), 25 mm (n = 39, 17.1%), and 27 mm (n = 123, 53.9%). The valve was successfully deployed in 99.1% of procedures. After implantation, the mean aortic gradient was 11.4 ± 5.4 mm Hg and aortic valve area 1.6 ± 0.5 cm(2). In-hospital mortality was 1.8% (n = 4). Complications included cardiac tamponade (1.8%), conversion to sternotomy (1.3%), stroke (3.9%), vascular access-related (7.0%), and acute kidney injury (7.9%). The incidence of moderate/severe aortic regurgitation was 0.8% (n = 2). A total of 31.8% of patients required new permanent pacemaker implantation. This analysis represents the largest published series on use of the LOTUS valve. Outcomes using this valve are excellent. In-hospital mortality is very low. Complication rates are low, and the LOTUS valve improves on first-generation valves, particularly with regard to residual aortic regurgitation. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. Narine, K; Chéry, Cyrille C; Goetghebeur, Els; Forsyth, R; Claeys, E; Cornelissen, Maria; Moens, L; Van Nooten, G The aim of this study was to evaluate and compare the calcification potential of kangaroo and porcine aortic valves after glutaraldehyde fixation at both low (0.6%) and high (2.0%) concentrations of glutaraldehyde in the rat subcutaneous model. To our knowledge this is the first report comparing the time-related, progressive calcification of these two species in the rat subcutaneous model. Twenty-two Sprague-Dawley rats were each implanted with two aortic valve leaflets (porcine and kangaroo) after fixation in 0.6% glutaraldehyde and two aortic valve leaflets (porcine and kangaroo) after fixation in 2% glutaraldehyde respectively. Animals were sacrificed after 24 h and thereafter weekly for up to 10 weeks after implantation. Calcium content was determined using inductively coupled plasma-mass spectrometry and confirmed histologically. Mean calcium content per milligram of tissue (dry weight) treated with 0.6 and 2% glutaraldehyde was 116.2 and 110.4 microg/mg tissue for kangaroo and 95.0 and 106.8 microg/mg tissue for porcine valves. Calcium content increased significantly over time (8.8 microg/mg tissue per week) and was not significantly different between groups. Regression analysis of calcification over time showed no significant difference in calcification of valves treated with 0.6 or 2% glutaraldehyde within and between the two species. Using the subcutaneous model, we did not detect a difference in calcification potential between kangaroo and porcine aortic valves treated with either high or low concentrations of glutaraldehyde. Copyright 2005 S. Karger AG, Basel. Oakley, Luke; Love, Kathleen; Ramirez, Alfredo; Boswell, Gilbert; Nayak, Keshav Aortic insufficiency from iatrogenic valve perforation from nonaortic valve operations is rarely reported despite the prevalence of these procedures. Rapid diagnosis of these defects is essential to prevent deterioration of cardiac function. In this paper, we describe a young man who reported to our institution after two open cardiac surgeries with new aortic regurgitation found to be due to an iatrogenic perforation of his noncoronary aortic valve cusp. This defect was not appreciated by previous intraoperative transesophageal echocardiography and was inadequately visualized on follow-up transthoracic and transesophageal echocardiograms. In contrast, cardiac gated computed tomography clearly visualized the defect and its surrounding structures. This case highlights the utility of cardiac gated computed tomography for cases of suspected valvular perforation when echocardiography is not readily available or inadequate imaging is obtained. Love, Kathleen; Ramirez, Alfredo; Boswell, Gilbert; Nayak, Keshav Aortic insufficiency from iatrogenic valve perforation from nonaortic valve operations is rarely reported despite the prevalence of these procedures. Rapid diagnosis of these defects is essential to prevent deterioration of cardiac function. In this paper, we describe a young man who reported to our institution after two open cardiac surgeries with new aortic regurgitation found to be due to an iatrogenic perforation of his noncoronary aortic valve cusp. This defect was not appreciated by previous intraoperative transesophageal echocardiography and was inadequately visualized on follow-up transthoracic and transesophageal echocardiograms. In contrast, cardiac gated computed tomography clearly visualized the defect and its surrounding structures. This case highlights the utility of cardiac gated computed tomography for cases of suspected valvular perforation when echocardiography is not readily available or inadequate imaging is obtained. PMID:24826290 Aggarwal, Shivani R; Clavel, Marie-Annick; Messika-Zeitoun, David; Cueff, Caroline; Malouf, Joseph; Araoz, Philip A; Mankad, Rekha; Michelena, Hector; Vahanian, Alec; Enriquez-Sarano, Maurice Aortic valve calcification (AVC) is the intrinsic mechanism of valvular obstruction leading to aortic stenosis (AS) and is measurable by multidetector computed tomography. The link between sex and AS is controversial and that with AVC is unknown. We prospectively performed multidetector computed tomography in 665 patients with AS (aortic valve area, 1.05±0.35 cm(2); mean gradient, 39±19 mm Hg) to measure AVC and to assess the impact of sex on the AVC-AS severity link in men and women. AS severity was comparable between women and men (peak aortic jet velocity: 4.05±0.99 versus 3.93±0.91 m/s, P=0.11; aortic valve area index: 0.55±0.20 versus 0.56±0.18 cm(2)/m(2); P=0.46). Conversely, AVC load was lower in women versus men (1703±1321 versus 2694±1628 arbitrary units; P<0.0001) even after adjustment for their smaller body surface area or aortic annular area (both P<0.0001). Thus, odds of high-AVC load were much greater in men than in women (odds ratio, 5.07; P<0.0001). Although AVC showed good associations with hemodynamic AS severity in men and women (all r>0.67; P<0.0001), for any level of AS severity measured by peak aortic jet velocity or aortic valve area index, AVC load, absolute or indexed, was higher in men versus women (all P≤0.01). In this large AS population, women incurred similar AS severity than men for lower AVC loads, even after indexing for their smaller body size. Hence, the relationship between valvular calcification process and AS severity differs in women and men, warranting further pathophysiological inquiry. For AS severity diagnostic purposes, interpretation of AVC load should be different in men and in women. Sundt, Thoralf M Despite more than a decade of intense investigation, controversy persists regarding appropriate triggers for aortic replacement in the setting of bicuspid aortic valve. The difficulty is that the data are inescapably imperfect. Although we can count individuals with bicuspid valve who suffer dissection, we have an insufficient understanding of the true denominator of individuals at risk to calculate the probability of dissection for an individual patient. In addition, our own decision-making process is subject to "denominator neglect" or focus on the fact of the occurrence of the event rather than on the risk of the occurrence. Furthermore, the data are inherently incomplete given the asymmetric nature of outcomes information. Specifically, although we can see those who did or did not dissect among the patients not undergoing surgery, the converse is not true; the tragedy of prophylactic surgery is that one cannot distinguish those who have benefited through prevention of dissection from those who paid the price of surgery but in whom dissection would never have occurred. Finally, we have data for only some of the critical determinants of dissection. Structural failure occurs when stresses exceed strengths. Aortic diameter gives us some insight into stress but we have little information on the material strength of the aorta. Early indications that patients undergoing aortic valve replacement for bicuspid valve had a significant risk of aortic dissection were followed by laboratory data showing histologic, biochemical, and mechanical abnormalities supporting an aggressive approach to resection; however, more recent clinical studies call this into question. Asano, Ryota; Nakano, Kiyoharu; Kodera, Kojiro; Sato, Atsuhiko; Kataoka, Go; Tatsuishi, Wataru; Kubota, Sayaka; Namiki, Shigetaka; Suzuki, Seiya A 53-year-old woman was developed congestive heart failure. She was diagnosed as having aortic coarctation, incompetent bicuspid aortic valve and an aberrant right subclavian artery by using echocardiography and enhanced computed tomography. Ankle brachial pressure index(ABI)in the right was 0.71 and 0.69 in the left. Blood pressure of the right arm was 60 mmHg lower than that of the left arm. To avoid perioperative adverse cardiac events due to a 2-staged operation, we performed ascending-descending aortic bypass and aortic valve replacement simultaneously through a median sternotomy. The heart was retracted cranially, and a vascular prosthesis was anastomosed to the descending aorta just above the diaphragm in an end-to-side manner. Then the graft was placed curvilinearly around the right atrium and was anastomosed to the ascending aorta. After the operation, the right and left ABI increased to 0.90 and 0.98 respectively. There was no pressure difference between the arms. The postoperative course was uneventful. Loftus, Patrick D; Erickson, Lance K; Everitt, Melanie D; Kaza, Aditya K We present the unusual case of a "disappearing" aortic valve in an infant with hypoplastic left heart syndrome (mitral and aortic stenosis) that underwent Norwood palliation at birth and subsequently a Glenn operation. Angiographic images at the time of operation showed no apparent insufficiency of the native aortic valve. Over the course of 14 months following operation, the patient developed significant cardiomegaly with a workup revealing severe native aortic valve insufficiency. Following orthotopic heart transplantation, examination of the explanted heart revealed a complete absence of native aortic valve leaflets. Pham, T; Martin, C; Elefteriades, J; Sun, W Studies have shown that patients harboring bicuspid aortic valve (BAV) or bovine aortic arch (BAA) are more likely than the general population to develop ascending aortic aneurysm (AsAA). A thorough quantification of the AsAA tissue properties for these patient groups may offer insights into the underlying mechanisms of AsAA development. Thus, the objective of this study was to investigate and compare the mechanical and microstructural properties of aortic tissues from AsAA patients with and without concomitant BAV or BAA. AsAA (n=20), BAV (n=20) and BAA (n=15) human tissues were obtained from patients who underwent elective AsAA surgery. Planar biaxial and uniaxial failure tests were used to characterize the mechanical and failure properties of the tissues, respectively. Histological analysis was performed to detect medial degenerative characteristics of aortic aneurysm. Individual layer thickness and composition were quantified for each patient group. The circumferential stress-strain response of the BAV samples was stiffer than both AsAA (p=0.473) and BAA (p=0.152) tissues at a low load. The BAV samples were nearly isotropic, while AsAA and BAA samples were anisotropic. The areal strain of BAV samples was significantly less than that of AsAA (p=0.041) and BAA (p=0.004) samples at a low load. The BAA samples were similar to the AsAA samples in both mechanical and failure properties. On the microstructural level, all samples displayed moderate medial degeneration, characterized by elastin fragmentation, cell loss, mucoid accumulation and fibrosis. The ultimate tensile strength of BAV and BAA sampleswere also found to decrease with age. Overall, the BAV samples were stiffer than both AsAA and BAA samples, and the BAA samples were similar to the AsAA samples. The BAV samples were thinnest, with less elastin than AsAA and BAA samples, which may be attributed to the loss of extensibility of these tissues at a low load. No apparent difference in failure mechanics among Szeto, Kai; Rodriguez-Rodriguez, Javier; Pastuszko, Peter; Nigam, Vishal; Lasheras, Juan C. It has been shown in clinical studies that patients with congenital bicuspid aortic valves (CBAVs) develop degenerative calcification of the leaflets at young ages compared to patients with the normal tricuspid aortic valves (TAVs). It has been hypothesized that the asymmetrical geometry of the leaflets in CBAVs, flow shear stresses (SS), disturbed flow, and excessive strain rate levels are possible causes for the early calcification and stenosis. Central to the validation of this hypothesis is the need to quantify the differences in strain rate levels between the BAVs and TAVs. We simulate the CBAVs by surgically stitching two of the leaflets of a porcine aortic valve together. To quantify strain differences, we performed in-vitro experiments in both trileaflet and bileaflet valves by tracking the motion of small ink dots marked on each leaflet surface. We then used phase-locked stereo photogrammetry to reconstruct at each instant of time the 3D surface of the leaflets and measure the strain rates in both radial and circumferential directions during the whole cardiac cycle. Our results indicate that the total strain rate of the simulated BAVs is about 15 to 20% higher than the normal leaflets of TAVs at systole. In the BAVs' case, the fused leaflet stretches radially up to 25% higher than the reference length. The excessive stretching in both directions in the fused leaflet results in large changes in the flow patterns and associated wall SS. Ciolina, F; Sedati, P; Zaccagna, F; Galea, N; Noce, V; Miraldi, F; Cavarretta, E; Francone, M; Carbone, I In patients affected by aortic valve stenosis (AS) it is mandatory to rule out coronary artery disease (CAD). The role of retrospectively ECG-gated 64-slice CT angiography (64-SCTA) was assessed in patients with AS referred for surgical valve replacement. Forty-two patients with AS underwent ECG-gated 64-SCTA of thoracic aorta, including the heart and coronary arteries, before surgical valve replacement. Images were evaluated by two independent readers and compared with surgical findings in terms of aortic valve calcification grading, valvular morphology, aortic valve annulus and sino-tubular junction diameters, and valvular area planimetry. Quantitative evaluation of cusps opening was also performed. Finally, the presence of CAD, thoracic aortic aneurysm and left ventricle hypertrophy were assessed. Visualization of the aortic valve without motion artefacts was possible in 38 patients (90.5%). Valvular morphology was correctly assessed in all cases (100%). 64-SCTA correctly determined aortic valve calcification grading and the aortic valve annulus and sinotubular junction diameters in 100% of cases. The aortic valve planimetric area was assessed in 38 cases (90.5%). Ascending aortic aneurysms requiring surgical replacement were detected in 12 patients (28.6%). Significant left ventricle hypertrophy was found in 30 patients (71%). Preoperative evaluation of patients undergoing surgical replacement for AS with 64-SCTA is feasible. 64-SCTA can rule out CAD and evaluate the status of the aortic valve and thoracic aorta in the same examination, obtaining relevant information for surgical planning. Karataş, Zehra; Karataş, Ahmet; Özlü, Tülay; Goksugur, Sevil B.; Varan, Birgül The use of antiepileptic drugs increases the risk of major congenital malformations during pregnancy. Here, we report an infant who had a history of in-utero carbamazepine exposure and who was born with a cardiac malformation. The infant was born at 39 weeks of gestation vaginally to an epileptic mother who had been treated with carbamazepine throughout her pregnancy. He was referred due to cardiac murmur in the second week of his life. The mother had not received folic acid supplementation. Transthoracic echocardiography revealed bicuspid aortic valve, mild aortic stenosis, patent ductus arteriosus, patent foramen ovale and the renal ultrasound revealed mild left hydronephrosis. Follow-up echocardiography performed 14 weeks later showed increased severity of aortic stenosis and percutaneous balloon aortic valvuloplasty was performed. To our knowledge, there is only one case report in the literature mentioning the association of a bicuspid aortic valve and aortic stenosis with oxcarbazepine exposure, which is a structural derivative of carbamazepine. However, there are no reports for association with carbamazepine itself. Bicuspid aorta and aortic stenosis may be among the cardiac malformations that result from the teratogenic effect of carbamazepine. PMID:25584038 Bernard, Y.; Meneveau, N.; Vuillemenot, A.; Magnin, D.; Anguenot, T.; Schiele, F.; Bassand, J. P. OBJECTIVE: To assess the reliability of aortic valve area planimetry by multiplane transoesophageal echocardiography (TOE) in aortic stenosis. DESIGN: Study of the diagnostic value of aortic valve area planimetry using multiplane TOE, compared with catheterisation and the continuity equation, both being considered as criterion standards. SETTING: University hospital. PATIENTS: 49 consecutive patients (29 male, 20 female, aged 44 to 82 years, average 66.6 (SD 8.5)), referred for haemodynamic evaluation of an aortic stenosis, were enrolled in a prospective study. From this sample, 37 patients were eligible for the final analysis. METHODS: Transthoracic and multiplane transoesophageal echocardiograms were performed within 24 hours before catheterisation. At transthoracic echo, aortic valve area was calculated by the continuity equation. At TOE, the image of the aortic valve opening was obtained with a 30-65 degrees rotation of the transducer. Numerical dynamic images were stored on optical discs for off-line analysis and were reviewed by two blinded observers. Catheterisation was performed in all cases and aortic valve area was calculated by the Gorlin formula. RESULTS: Feasibility of the method was 92% (48/52). The agreement between aortic valve area measured at TOE (mean 0.88 (SD 0.35) cm2) and at catheterisation (0.79 (0.24) cm2) was very poor. The same discrepancies were found between TOE and the continuity equation (0.72 (0.26) cm2). TOE planimetry overestimated aortic valve area determined by the two other methods. Predictive positive and negative values of planimetry to detect aortic valve area < 0.75 cm2 were 62% (10/16) and 43% (9/21) respectively. CONCLUSIONS: Planimetry of aortic valve area by TOE is difficult and less accurate than the continuity equation for assessing the severity of aortic stenosis. Images PMID:9290405 Jander, Nikolaus; Gohlke-Bärwolf, Christa; Bahlmann, Edda; Gerdts, Eva; Boman, Kurt; Chambers, John B; Egstrup, Kenneth; Nienaber, Christoph A; Pedersen, Terje R; Ray, Simon; Rossebø, Anne B; Willenheimer, Ronnie; Kienzle, Rolf-Peter; Wachtell, Kristian; Neumann, Franz-Josef; Minners, Jan To account for differences in body size in patients with aortic stenosis, aortic valve area (AVA) is divided by body surface area (BSA) to calculate indexed AVA (AVAindex). Cut-off values for severe stenosis are <1.0 cm2 for AVA and <0.6 cm2/m2 for AVAindex. To investigate the influence of indexation on the prevalence of severe aortic stenosis and on the predictive accuracy regarding clinical outcome. Echocardiographic and anthropometric data from a retrospective cohort of 2843 patients with aortic stenosis (jet velocity >2.5 m/s) and from 1525 patients prospectively followed in the simvastatin and ezetimibe in aortic stenosis (SEAS) trial were analysed. The prevalence of severe stenosis increased with the AVAindex criterion compared to AVA from 71% to 80% in the retrospective cohort, and from 29% to 44% in SEAS (both p<0.001). Overall, the predictive accuracy for aortic valve events was virtually identical for AVA and AVAindex in the SEAS population (mean follow-up of 46 months; area under the receiver operating characteristic curve: 0.67 (95% CI 0.64 to 0.70) vs. 0.68 (CI 0.65 to 0.71) (NS). However, 213 patients additionally categorised as severe by AVAindex experienced significantly less valve related events than those fulfilling only the AVA criterion (p<0.001). Indexing AVA by BSA (AVAindex) significantly increases the prevalence of patients with criteria for severe stenosis by including patients with a milder degree of the disease without improving the predictive accuracy for aortic valve related events. Grubitzsch, Herko; Tarar, Waharat; Claus, Benjamin; Gabbieri, Davide; Falk, Volkmar; Christ, Torsten Prosthetic valve endocarditis is the most severe form of infective endocarditis. This study assessed the risks and challenges of surgery for aortic prosthetic valve endocarditis. In total, 116 consecutive patients (98 males, age 65.2±12.7years), who underwent redo-surgery for active aortic prosthetic valve endocarditis between 2000 and 2014, were reviewed. Cox regression analysis was used to identify factors for aortic root destructions as well as for morbidity and mortality. Median follow-up was 3.8 years (0-13.9 years). Aortic root destructions (42 limited and 29 multiple lesions) were associated with early prosthetic valve endocarditis and delayed diagnosis (≥14 d), but not with mortality. There were 16 (13.8%) early (≤30 d) and 32 (27.6%) late (>30 days) deaths. Survival at 1, 5, and 10 years was 72±4.3%, 56±5.4%, and 46±6.4%, respectively. The cumulative incidence of death, reinfection, and reoperation was 19.0% at 30days and 36.2% at 1year. Delayed diagnosis, concomitant procedures, and EuroSCORE II >20% were predictors for early mortality and need for mechanical circulatory support, age >70years, and critical preoperative state were predictors for late mortality. In their absence, survival at 10 years was 70±8.4%. Reinfections and reoperations occurred more frequently if ≥1 risk factor for endocarditis and aortic root destructions were present. At 10 years, freedom from reinfection and reoperation was 89±4.2% and 91±4.0%. The risks of death, reinfection, and reoperation are significant within the first year after surgery for aortic prosthetic valve endocarditis. Early diagnosis and aortic root destructions are the most important challenges, but advanced age, critical preoperative state, and the need for mechanical circulatory support determine long-term survival. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B Stephens, Elizabeth H.; Post, Allison D.; Laucirica, Daniel R.; Grande-Allen, K. Jane At birth, the mechanical environment of valves changes radically as fetal shunts close and pulmonary and systemic vascular resistances change. Given that valves are reported to be mechanosensitive, we investigated remodeling induced by perinatal changes by examining compositional and structural differences of aortic and mitral valves (AVs, MVs) between 2-day-old and 3rd fetal trimester porcine valves using immunohistochemistry and Movat pentachrome staining. Aortic valve composition changed more with birth than the MV, consistent with a greater change in AV hemodynamics. At 2 days, AV demonstrated a trend of greater versican and elastin (P = 0.055), as well as greater hyaluronan turnover (hyaluronan receptor for endocytosis, P = 0.049) compared with the 3rd-trimester samples. The AVs also demonstrated decreases in proteins related to collagen synthesis and fibrillogenesis with birth, including procollagen I, prolyl 4-hydroxylase, biglycan (all P ≤ 0.005), and decorin (P = 0.059, trend). Both AVs and MVs demonstrated greater delineation between the leaflet layers in 2-day-old compared with 3rd-trimester samples, and AVs demonstrated greater saffron-staining collagen intensity, suggesting more mature collagen in 2-day-old compared with 3rd-trimester samples (each P < 0.05). The proportion of saffron-staining collagen also increased in AV with birth (P < 0.05). The compositional and structural changes that occur with birth, as noted in this study, likely are important to proper neonatal valve function. Furthermore, normal perinatal changes in hemodynamics often do not occur in congenital valve disease; the corresponding perinatal matrix maturation may also be lacking and could contribute to poor function of congenitally malformed valves. PMID:20536360 Ali, Omar; Salinger, Michael H; Levisay, Justin P; Feldman, Ted Aortic insufficiency (AI) after transcatheter aortic valve replacement (TAVR) is difficult to manage when associated with congestive heart failure. AI after balloon aortic valvuloplasty (BAV) may be catastrophic, especially in patients who are not candidates for TAVR. We describe the use of urgent temporary pacing, followed by permanent pacing, to increase the heart rate to diminish diastolic filling time for the short term management of AI after BAV or TAVR. The strategy is particularly useful in patients who already have permanent pacemakers, which are common in this population. Thaden, Jeremy J; Nkomo, Vuyisile T; Suri, Rakesh M; Maleszewski, Joseph J; Soderberg, Daniel J; Clavel, Marie-Annick; Pislaru, Sorin V; Malouf, Joseph F; Foley, Thomas A; Oh, Jae K; Miller, Jordan D; Edwards, William D; Enriquez-Sarano, Maurice Calcific aortic valve stenosis (AS) is purportedly associated with less calcium burden in women than in men. We sought to examine sex-related differences and correlates of surgically excised aortic valve weight (AVW) in pure AS. Clinical and echocardiographic characteristics of 888 consecutive patients who underwent aortic valve replacement for severe AS were correlated to AVW, and in 126 patients, AVW was also correlated to computed tomography aortic valve calcium (AVC) score. Women and men had similar indexed valve area (0.42 ± 0.09 vs. 0.42 ± 0.07 cm (2)/m(2), P = 0.95) and mean systolic gradient (53 ± 15 vs. 52 ± 13 mmHg, P = 0.11), but women had higher New York Heart Association class (2.63 ± 0.70 vs. 2.50 ± 0.70, P = 0.01) and less prevalent coronary artery disease (38 vs. 52%, P < 0.0001). Aortic valve weight was lower in women (1.94 ± 0.88 vs. 3.08 ± 1.32 g, P < 0.0001) even when indexed to body surface area (1.09 ± 0.48 vs. 1.48 ± 0.62 g/m(2), P < 0.0001) or left ventricular outflow tract (LVOT) area (0.54 ± 0.23 vs. 0.71 ± 0.29 g/cm(2), P < 0.0001). Using multivariate analysis, male sex (P < 0.0001), bicuspid valve (P < 0.0001), and larger LVOT area (P < 0.0001) were the major determinants of increased AVW, along with current cigarette smoking (P = 0.007). Diabetes (P = 0.004) and hypertension (P = 0.03) were independently associated with lower AVW. Aortic valve calcium correlated well with AVW (r = 0.81, P < 0.0001) and was lower in women than in men (2520 ± 1199 vs. 3606 ± 1632 arbitrary units, P < 0.0001). Despite the same degree of AS severity, women have less AVC and lower AVW compared with men, irrespective of valve morphology. Aortic valve calcium is correlated to excised AVW. Hypertension, diabetes, and current cigarette smoking were independently associated with AVW. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: [email protected]. Pal, Jay D; McCabe, James M; Dardas, Todd; Aldea, Gabriel S; Mokadam, Nahush A The development of new aortic insufficiency after a period of support with a left ventricular assist device can result in progressive heart failure symptoms. Transcatheter aortic valve repair can be an effective treatment in selected patients, but the lack of aortic valve calcification can result in unstable prostheses or paravalvular leak. We describe a technique of deploying a self-expanding CoreValve (Medtronic, Minneapolis, MN, USA) into the aortic annulus, followed by a balloon-expandable SAPIEN-3 (Edwards, Irvine, CA, USA). Drolet, Marie-Claude; Couet, Jaques; Arsenault, Marie Aortic valve sclerosis is fairly common and is currently seen as a marker of systemic atherosclerosis. For unclear reasons only a minority of those sclerotic valves will evolve to become stenotic suggesting that atherogenic factors alone are insufficient to explain the development of valve stenosis. We had reported in a model of cholesterol fed rabbits that a combination of high cholesterol with vitamin D supplementation was necessary to induce valve stenosis and significant calcium deposition whereas high cholesterol alone only induced a sclerosis of the valve. In this study, we further evaluated the role of vitamin D treatment in the development of aortic valve disease (sclerosis or stenosis) in this rabbit model. Rabbits were divided in 4 groups followed for 12 weeks: 1) no treatment; 2) cholesterol-enriched diet, 3) cholesterol-enriched diet + vitamin D2 (VD; 50000IU, daily) 4) VD alone for 12 weeks. Echocardiographic assessment of the aortic valve was done at baseline, and every 4 weeks thereafter. Aortic valve area, maximal and mean transvalvular gradients were recorded and compared over time. Immunohistological study of the valves of AS rabbits was also realized for several classical atherosclerosis markers. Vitamin D2 treated animal did not develop any stenosis of the valve despite increased echogenicity due to diffuse calcium deposits on the leaflets without any atherosclerotic lesions. Only the combination of high cholesterol with VD resulted in a decrease of aortic valve area. Immunohistological analysis of aortic valves from VD rabbits showed the presence of calcium deposits, T-cell infiltration in addition to positive labeling for alpha-smooth muscle cell actin. We did not observe macrophage infiltration in aortic valve leaflets of VD rabbits. Hypercholesterolemia or vitamin D supplements alone could not induce aortic valve stenosis in our animal model whereas the combination resulted in a decreased aortic valve area. These findings support the Wang, Qian; Kodali, Susheel; Primiano, Charles; Sun, Wei Objectives Aortic root rupture is one of the most severe complications of transcatheter aortic valve implantation (TAVI). The mechanism of this adverse event remains mostly unknown. The purpose of this study was to obtain a better understanding of the biomechanical interaction between the tissue and stent for patients with a high risk of aortic rupture. Methods We simulated the stent deployment process of three TAVI patients with high aortic rupture risk using finite element method. The first case was a retrospective analysis of an aortic rupture case, while the other two cases were prospective studies, which ended with one cancelled procedure and one successful TAVI. Simulation results were evaluated for the risk of aortic root rupture, as well as coronary artery occlusion, and paravalvular leak. Results For Case 1, the simulated aortic rupture location was the same as clinical observations. From the simulation results, it can be seen that the large calcified spot on the interior of the left coronary sinus between coronary ostium and the aortic annulus was pushed by the stent, causing the aortic rupture. For Case 2 and Case 3, predicated results from the simulations were presented to the clinicians at pre-procedure meetings; and they were in agreement with clinician’s observations and decisions. Conclusions Our results indicated that the engineering analysis could provide additional information to help clinicians evaluate complicated, high risk aortic rupture cases. Since a systematic study of a large patient cohort of aortic rupture is currently not available (due to the low occurrence rate) to clearly understand underlying rupture mechanisms, case by case engineering analysis is recommended for evaluating patient-specific aortic rupture risk. PMID:24736808 Di Gioacchino, Lorena; Balestrini, Fabrizio Enterococci are common organisms associated with endocarditis, but infection by Enterococcus durans is very rare. To our knowledge, only 3 cases have been reported in the medical literature, and all 3 have involved native valves. Here we publish the first reported case (to our knowledge) of E. durans endocarditis in association with a bioprosthetic aortic valve. After the organism and its antibiotic susceptibility were identified, the 74-year-old male patient was treated successfully with teicoplanin and gentamicin, over a course of 6 weeks. PMID:27127436 VeDepo, Mitchell C; Buse, Eric E; Quinn, Rachael W; Williams, Todd D; Detamore, Michael S; Hopkins, Richard A; Converse, Gabriel L Decellularized heart valves have great potential as a stand-alone valve replacement or as a scaffold for tissue engineering heart valves. Before decellularized valves can be widely used clinically, regulatory standards require pre-clinical testing in an animal model, often sheep. Numerous decellularization protocols have been applied to both human and ovine valves; however, the ways in which a specific process may affect valves of these species differently have not been reported. In the current study, the comparative effects of decellularization were evaluated for human and ovine aortic valves by measuring mechanical and biochemical properties. Cell removal was equally effective for both species. The initial cell density of the ovine valve leaflets (2036±673cells/mm(2)) was almost triple the cell density of human leaflets (760±386cells/mm(2); p<0.001). Interestingly, post-decellularization ovine leaflets exhibited significant increases in biaxial areal strain (p<0.001) and circumferential peak stretch (p<0.001); however, this effect was not observed in the human counterparts (p>0.10). This species-dependent difference in the effect of decellularization was likely due to the higher initial cellularity in ovine valves, as well as a significant decrease in collagen crosslinking following the decellularization of ovine leaflets that was not observed in the human leaflet. Decellularization also caused a significant decrease in the circumferential relaxation of ovine leaflets (p<0.05), but not human leaflets (p>0.30), which was credited to a greater reduction of glycosaminoglycans in the ovine tissue post-decellularization. These results indicate that an identical decellularization process can have differing species-specific effects on heart valves. Sharma, Munish; Mascarenhas, Daniel A.N. Aortic valve replacement (AVR) remains the cornerstone of treatment for symptomatic critical aortic stenosis (AS). It is a Class I indication that symptomatic patients with critical AS undergo either surgical or transcatheter aortic valve replacement (TAVR). We present a patient with critical AS and new angina that was managed successfully with percutaneous coronary intervention (PCI) of the Right coronary artery. Physicians should consider that not all patients with critical AS and angina necessarily require AVR. Concomitant pathology leading to the symptoms should be carefully ruled out. This leads to a less invasive, cost effective care plan especially in patients with advanced age and comorbidities for which any type of surgical valvular intervention may pose high risk. PMID:27994841 Shackelford, Anthony G.; Relle, Margaret A.; Lombardi, Sarah A. Abstract: In adults over 65 years of age, aortic valve stenosis has been found to be present in 2–9% within this group. Furthermore, aortic valve replacements in patients whom have had a previous coronary artery bypass grafting surgery have a mortality rate as high as 18%. A non-conventional effective surgical approach of bypassing the aortic valve by inserting an apicoaortic valve conduit (AVC) connecting the left ventricular apex to the descending thoracic aorta has been previously documented. We describe the case of a successful implantation of an AVC in a 64-year-old Caucasian male using cardiopulmonary bypass. PMID:26834287 Shackelford, Anthony G; Relle, Margaret A; Lombardi, Sarah A In adults over 65 years of age, aortic valve stenosis has been found to be present in 2-9% within this group. Furthermore, aortic valve replacements in patients whom have had a previous coronary artery bypass grafting surgery have a mortality rate as high as 18%. A non-conventional effective surgical approach of bypassing the aortic valve by inserting an apicoaortic valve conduit (AVC) connecting the left ventricular apex to the descending thoracic aorta has been previously documented. We describe the case of a successful implantation of an AVC in a 64-year-old Caucasian male using cardiopulmonary bypass. Sarı, Cenk; Durmaz, Tahir; Karaduman, Bilge Duran; Keleş, Telat; Bayram, Hüseyin; Baştuğ, Serdal; Özen, Mehmet Burak; Bayram, Nihal Akar; Bilen, Emine; Ayhan, Hüseyin; Kasapkara, Hacı Ahmet; Bozkurt, Engin Transcatheter aortic valve implantation (TAVI) was introduced as an alternative treatment for patients with severe symptomatic aortic stenosis for whom surgery would be high-risk. Prosthetic aortic valve endocarditis is a serious complication of surgical AVR (SAVR) with high morbidity and mortality. According to recent cases, post-TAVI prosthetic valve endocarditis (PVE) seems to occur very rarely. We present the case of a 75-year-old woman who underwent TAVI (Edwards Saphien XT) with an uneventful postoperative stay. She was diagnosed with endocarditis using three dimensional (3D) echocardiography on the TAVI device 7 months later and she subsequently underwent surgical aortic valve replacement. Little experience of the interpretation of transoesophageal echocardiography (TEE) and the clinical course and effectiveness of treatment strategies in post-TAVI endocarditis exists. We report a case of PVE in a TAVI patient which was diagnosed with three-dimensional transoesophageal echocardiography (3DTEE). Copyright © 2016 Hellenic Cardiological Society. Published by Elsevier B.V. All rights reserved. Keeling, W Brent; Leshnower, Bradley G; Binongo, Jose; Lasanajak, Yi; McPherson, LaRonica; Chen, Edward P The David V valve-sparing aortic root replacement (VSRR) is an established and durable method of root reconstruction for varying pathologies. However, the impact of the severity of preoperative aortic regurgitation (AR) on long-term durability remains unclear. The purpose of this research was to investigate the impact of the degree of preoperative AR on midterm durability following VSRR. A retrospective review of the adult cardiac surgical database at a single academic center was undertaken from 2005 to 2015 for 223 adult patients who underwent VSRR. Patients were followed annually with echocardiograms, and a prospectively maintained database kept track of patient data. Follow-up was 97.7% complete, and the median echocardiographic follow-up was 25.5 months (range, 1 to 123 months). Patients with preoperative AR less than or equal to 2 were compared with patients with AR greater than 2 to determine the impact of preoperative AR upon valve repair durability. There were 223 patients who underwent VSRR during the study period, including 114 (51.1%) who required concomitant cusp repair. The operative mortality was 5 (2.2%). Ninety-seven patients (43.5%) had preoperative AR greater than 2. A total of 213 patients (95.5%) were available for long-term follow-up; of these patients, 7 (3.3%) had AR greater than 2. Fifty-two patients had a bicuspid aortic valve (22 AR ≤2 and 30 AR >2; p = 0.02). Patients with preoperative AR greater than 2 experienced greater reverse left ventricular remodeling and increases in left ventricular ejection fraction than did patients with preoperative AR less than or equal to 2 (p < 0.01). The midterm freedom from AR greater than 2 was similar for both preoperative AR groups (p = 0.57). The 8-year freedom from AR greater than 2 was 89.1% (95% confidence interval, 55.3% to 97.8%) for patients with preoperative AR less than or equal to 2 and 92.7% (95% confidence interval, 78.8% to 97.6%) for preoperative AR greater than 2. Five patients (2 Lambrechts, David L.; Wellens, Francis; Vercoutere, Rik A.; De Geest, Raf We report a case of life-threatening aortic transection with concomitant mitral papillary muscle rupture and severe lung contusion caused by a failed parachute jump. This blunt thoracic injury was treated by early stabilization with extracorporeal membrane oxygenation followed by successful delayed graft repair of the descending aorta and mitral valve replacement with a mechanical prosthesis. (Tex Heart Inst J 2003;30:65–7) PMID:12638675 Woo, Y Joseph; Grand, Todd J; Weiss, Stuart J Robotic technology has been applied to multiple cardiac surgical procedures. Purported benefits include decreased tissue trauma, reduced postoperative bleeding, fewer blood product transfusions, and shorter lengths of stay. We describe the case of a 50-year-old man with an incidentally discovered 1-cm mobile mass on the edge of the aortic valve noncoronary leaflet. The patient underwent robotic minimally invasive resection. The pathologic examination revealed papillary fibroelastoma. Zeng, Qingchun; Song, Rui; Fullerton, David A.; Ao, Lihua; Zhai, Yufeng; Li, Suzhao; Ballak, Dov B.; Cleveland, Joseph C.; Reece, T. Brett; McKinsey, Timothy A.; Xu, Dingli; Dinarello, Charles A.; Meng, Xianzhong Calcific aortic valve disease is a chronic inflammatory process, and aortic valve interstitial cells (AVICs) from diseased aortic valves express greater levels of osteogenic factors in response to proinflammatory stimulation. Here, we report that lower cellular levels of IL-37 in AVICs of diseased human aortic valves likely account for augmented expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP) following stimulation of Toll-like receptor (TLR) 2 or 4. Treatment of diseased AVICs with recombinant human IL-37 suppresses the levels of BMP-2 and ALP as well as calcium deposit formation. In mice, aortic valve thickening is observed when exposed to a TLR4 agonist or a high fat diet for a prolonged period; however, mice expressing human IL-37 exhibit significantly lower BMP-2 levels and less aortic valve thickening when subjected to the same regimens. A high fat diet in mice results in oxidized low-density lipoprotein (oxLDL) deposition in aortic valve leaflets. Moreover, the osteogenic responses in human AVICs induced by oxLDL are suppressed by recombinant IL-37. Mechanistically, reduced osteogenic responses to oxLDL in human AVICs are associated with the ability of IL-37 to inhibit NF-κB and ERK1/2. These findings suggest that augmented expression of osteogenic factors in AVICs of diseased aortic valves from humans is at least partly due to a relative IL-37 deficiency. Because recombinant IL-37 suppresses the osteogenic responses in human AVICs and alleviates aortic valve lesions in mice exposed to high fat diet or a proinflammatory stimulus, IL-37 has therapeutic potential for progressive calcific aortic valve disease. PMID:28137840 Blackstone, E H; Kirklin, J W; Pluth, J R; Turner, M E; Parr, G V Four hundred seventy-five patients underwent aortic valve replacement with the Braunwald-Cutter ball-valve prosthesis at two institutions. The early (30-day) hospital mortality was 4.7% for those with isolated aortic valve replacement and 6.9% for the entire group. For the former, 5-year actuarial survival of the hospital survivors was 72 +/- 5.7%; for the latter group it was 71 +/- 4.4%. Eleven patients (5 since the date of follow-up inquiry) have suffered poppet escape, 9 of whom died. The actuarial incidence of known poppet escape is 4 +/- 2.6% at 47 months; when the 5 patients suffering poppet escape since the date of follow-up inquiry are included, with certain assumptions, the incidence is 3.7 +/- 1.14%. The projected probability of poppet escape using all 11 patients is 12.2% at 5 years; the 70% confidence bands of projected probability of poppet escape separate from those of the risk of re-replacement at 61 months. This and other analyses indicate that in general, patients with the Braunwald-Cutter aortic prosthesis should have it replaced 4 1/2 to 5 years after its insertion. Shemin, R J; Guadiani, V A; Conkle, D M; Morrow, A G During a 15-year period from January 1962 through December 1976, 42 patients who had undergone a previous aortic valve replacement underwent reoperation. The mean interval between operations was 4.4 years. The indications for reoperation were aortic regurgitation resulting from mechanical malfunction (12 patients), ball variance (15 patients), perivalvular leaks (five patients), prosthetic stenosis (eight patients), anemia (one patient), and recurrent emboli (one patient). The indications were characteristic of a specific valve series. The most common reoperation was aortic valve replacement (29/42), which had a 10.3% operative mortality. Poppet change (10/42) carried a 10% operative mortality and no operative deaths followed suture closure of perivalvular leaks. Eighty-eight percent of patients alive six months after reoperation were New York Heart Association functional class 1 or 2. At last follow-up, 95% of surviving patients were still functional class 1 or 2, with a mean cumulative survival of 4.7 years after reoperation. This experience demonstrates that those patients surviving long enough to undergo reoperation can expect a reasonable operative risk, long-term survival, and excellent clinical improvement. Nijenhuis, Vincent J; Bennaghmouch, Naoual; van Kuijk, Jan-Peter; Capodanno, Davide; ten Berg, Jurriën M Transcatheter aortic valve implantation (TAVI) is an established treatment option for symptomatic patients with severe aortic valvular disease who are not suitable for conventional surgical aortic valve replacement. Despite improving experience and techniques, ischaemic and bleeding complications after TAVI remain prevalent and impair survival in this generally old and comorbid-rich population. Due to changing aetiology of complications over time, antiplatelet and anticoagulant therapy after TAVI should be carefully balanced. Empirically, a dual antiplatelet strategy is generally used after TAVI for patients without an indication for oral anticoagulation (OAC; e. g. atrial fibrillation, mechanical mitral valve prosthesis), including aspirin and a thienopyridine. For patients on OAC, a combination of OAC and aspirin or thienopyridine is generally used. This review shows that current registries are unfit to directly compare antithrombotic regimens. Small exploring studies suggest that additional clopidogrel after TAVI only affects bleeding and not ischemic complications. However, these studies are lack in quality in terms of Cochrane criteria. Currently, three randomised controlled trials are recruiting to gather more knowledge about the effects of clopidogrel after TAVI. Benevento, Emilia; Djebbari, Abdelghani; Keshavarz-Motamed, Zahra; Cecere, Renzo; Kadem, Lyes Aortic valve bypass (AVB) has been shown to be a viable solution for patients with severe aortic stenosis (AS). Under this circumstance, the left ventricle (LV) has a double outlet. The objective was to develop a mathematical model capable of evaluating the hemodynamic performance following the AVB surgery. A mathematical model that captures the interaction between LV, AS, arterial system, and AVB was developed. This model uses a limited number of parameters that all can be non-invasively measured using patient data. The model was validated using in vivo data from the literature. The model was used to determine the effect of different AVB and AS configurations on flow proportion and pressure of the aortic valve and the AVB. Results showed that the AVB leads to a significant reduction in transvalvular pressure gradient. The percentage of flow through the AVB can range from 55.47% to 69.43% following AVB with a severe AS. LV stroke work was also significantly reduced following the AVB surgery and reached a value of around 1.2 J for several AS severities. Findings of this study suggest: 1) the AVB leads to a significant reduction in transvalvular pressure gradients; 2) flow distribution between the AS and the AVB is significantly affected by the conduit valve size; 3) the AVB leads to a significant reduction in LV stroke work; and 4) hemodynamic performance variations can be estimated using the model. PMID:25881082 Aslan, Abdullah Nabi; Baştuğ, Serdal; Kasapkara, Hacı Ahmet; Ayhan, Hüseyin; Süygün, Hakan; Keleş, Telat; Durmaz, Tahir; Akar Bayram, Nihal; Bilen, Emine; Bozkurt, Engin Transcatheter aortic valve implantation (TAVI) has shown promising results in patients with severe aortic stenosis (AS) at high risk for open heart surgery. We aimed to evaluate outcomes of patients who underwent TAVI with Edwards SAPIEN 3 Transcatheter Heart Valve (S3), a second-generation TAVI device. Between November 2014 and June 2016, 31 high-risk patients received balloon-expandable S3 valve at Atatürk Training and Research Hospital that has the largest case series in Turkey. Mean age of the patients was 76.1±12.6 years. Mean Society of Thoracic Surgeons and logistic European System for Cardiac Operative Risk Evaluation scores were 7.8%±3.1 and 31.4%±17.6, respectively. S3 valve was implanted in 27 patients via transfemoral approach and via trans-subclavian approach in 4 patients under local (n=29) or general (n=2) anesthesia. Procedural success rate was 100% (23 mm, n=7; 26 mm, n=16; 29 mm, n=8). Paravalvular aortic regurgitation (PAR) was absent or trivial in 29 (93.6%) patients and mild in 2 (6.4%) patients. Permanent pacemaker implantation (PPI) was required in 2 (6.4%) patients during the procedure, and in-hospital mortality occurred in 1 (3.2%) of those 2 patients. S3 valve is associated with higher rate of device success and lower incidence of PAR, peripheral vascular complications, and need for new PPI. Berdajs, Denis; Mosbahi, Selim; Ferrari, Enrico; Charbonnier, Dominique; von Segesser, Ludwig K In this study, the effect of aortic valve (AV) pathology on local hemodynamic conditions was evaluated as a potential trigger for the onset of acute type A and B aortic dissection. A time- and pressure-related four-dimensional (4-D) computed fluid dynamic model of the aorta was established. In an experimental setup, AV stenosis and AV insufficiency were created. 4-D pressure-related geometry of the aortic root (AR) with valve insufficiency and valve stenosis were determined by high-fidelity (200 Hz) microsonometric crystals. Flow and pressure were obtained at the left ventricle, ascending aorta, and aortic arch. Expansion of the AR in AV insufficiency was higher with expansion in AV stenosis, at peak ejection, and at the end of systole. In AV insufficiency, there was low shear stress (0 to 0.6 Pa), turbulent flow, and high pressure (80 to 95 mm Hg) at the anterior wall of the ascending aorta, at the proximal aortic arch, and at the aortic isthmus. In stenosis, high shear stress (>2 Pa) and high pressure (>95 mm Hg) were found at the ascending aorta and at the bifurcation of the brachiocephalic trunk. In AV insufficiency, low shear stresses and turbulent flow regions were documented at the traditional levels of entry tears for acute type A and B dissection. In AV stenosis, high shear stress with elevated pressure at the ascending aorta may be a trigger element for vessel dilatation, aneurysm formation, and intimal tear, which is typical for type A aortic dissection. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved. Yu, Shujie; Yu, Xianguan; Zhou, Bin; Liu, Dinghui; Wang, Min; Zhang, Hui; Qian, Xiaoxian Tsutsugamushi disease is a zoonotic disease caused by Orientia tsutsugamushi in which humans are accidental hosts. Infective endocarditis associated with Tsutsugamushi disease has not been previously reported. We are describing a case of Tsutsugamushi disease presenting with aortic valve endocarditis. The clinical data of a 67-year-old female with O. tsutsugamushi-induced aortic valve endocarditis was summarized retrospectively and analyzed with a literature review. Treatment of O. tsutsugamushi-induced aortic valve endocarditis with chloramphenicol is recommended. PMID:28078179 Lai, Ka Sing Paris; Herrmann, Nathan; Saleem, Mahwesh; Lanctôt, Krista L. Severe aortic stenosis is the most common valvular heart disease in the elderly in the Western world and contributes to a large proportion of all deaths over the age of 70. Severe aortic stenosis is conventionally treated with surgical aortic valve replacement; however, the less invasive transcatheter aortic valve implantation (TAVI) is suggested for those at high surgical risk. While TAVI has been associated with improved survival and favourable outcomes, there is a higher incidence of cerebral microembolisms in TAVI patients. This finding is of concern given mechanistic links with cognitive decline, a symptom highly prevalent in those with cardiovascular disease. This paper reviews the literature assessing the possible link between TAVI and cognitive changes. Studies to date have shown that global cognition improves or remains unchanged over 3 months following TAVI while individual cognitive domains remain preserved over time. However, the association between TAVI and cognition remains unclear due to methodological limitations. Furthermore, while these studies have largely focused on memory, cognitive impairment in this population may be predominantly of vascular origin. Therefore, cognitive assessment focusing on domains important in vascular cognitive impairment, such as executive dysfunction, may be more helpful in elucidating the association between TAVI and cognition in the long term. PMID:25785192 [Dehiscence of the Pericardial Patch, after Surgical Treatment of Active Infective Aortic Valve Endocarditis with Reconstruction of the Aortic Annulus Using a Glutaraldehyde-treated Autologous Pericardium]. Yoshida, Kazufumi; Fukunaga, Naoto; Koizumi, Shigeki; Nishiya, Kenta; Matsuda, Yasuhiro; Ishigami, Masanosuke; Nagasawa, Atsushi; Sakata, Ryuzo; Koyama, Tadaaki A 50-year-old man was admitted with fever and chill sensation 6 months ago. Transthoracic echocardiography (TTE) showed left and right coronary cusp prolapses and a thickened tissue of the aortic curtain. Congestive heart failure due to active infective aortic valve endocarditis was diagnosed, and he underwent aortic valve replacement. The aortic annulus was reconstructed using a glutaraldehydetreated autologous pericardium. Six months after surgery, TTE showed severe aortic regurgitation and saccular change in the aortic annulus. Transesophageal echocargiography showed some echo free space from left to noncoronary cusp and abnormal movement of the prosthetic valve annulus. Intraoperative examination showed dehiscence of the pericardial patch from the aortic wall, but no finding of infection. Aortic valve rereplacement was performed with reconstruction of the aortic annulus using a bovine pericardium. To prevent the dehiscence of the pericardial patch from the aortic wall, sutures fixing the prosthetic valve were passed from outside of the aortic wall. Karimi, Ashkan; Pourafshar, Negiin; Park, Ki E; Choi, Calvin Y; Mogali, Kiran; Stinson, Wade W; Manning, Eddie W; Bavry, Anthony A A 79-year-old man underwent trans-catheter aortic valve replacement for symptomatic severe aortic stenosis with a 26-mm Edwards SAPIEN XT valve. Immediately after valve deployment there was moderate amount of paravalvular leak. Post-dilation was performed with an additional 2 cc of volume, and the paravalvular leak was reduced to trace. Nine months later, trans-thoracic echocardiography revealed moderate to severe paravalvular leak and possible aortic migration of the valve. The patient was brought back for the treatment of the paravalvular leak which was suspected to be due to valve migration. However, fluoroscopy and trans-esophageal echocardiography showed good valve position. Measurement of late valve recoil in the Coplanar view using cine-angiographic analysis software showed that the lower third of the valve had the greatest late recoil (-1.74 mm, 6.55%), which presumably accounted for the progression of the paravalvular leak. Valve-in-valve trans-catheter aortic valve replacement was performed with a 26-mm SAPIEN 3 valve and the paravalvular leak was reduced to trace. This case displays late recoil as a likely mechanism for development of paravalvular leak after SAPIEN XT valve implantation. Our case illustrates that late recoil needs to be systematically evaluated in future studies, especially when trans-catheter aortic valve replacement is being expanded to lower risk and younger patients for whom the longevity and long-term performance of these valves is of critical importance. Yutzey, Katherine E; Demer, Linda L; Body, Simon C; Huggins, Gordon S; Towler, Dwight A; Giachelli, Cecilia M; Hofmann-Bowman, Marion A; Mortlock, Douglas P; Rogers, Melissa B; Sadeghi, Mehran M; Aikawa, Elena Calcific aortic valve disease (CAVD) is increasingly prevalent worldwide with significant morbidity and mortality. Therapeutic options beyond surgical valve replacement are currently limited. In 2011, the National Heart Lung and Blood Institute assembled a working group on aortic stenosis. This group identified CAVD as an actively regulated disease process in need of further study. As a result, the Alliance of Investigators on CAVD was formed to coordinate and promote CAVD research, with the goals of identifying individuals at risk, developing new therapeutic approaches, and improving diagnostic methods. The group is composed of cardiologists, geneticists, imaging specialists, and basic science researchers. This report reviews the current status of CAVD research and treatment strategies with identification of areas in need of additional investigation for optimal management of this patient population. © 2014 American Heart Association, Inc. Tsai, Yi-Chin; Niles, Natasha; Tchantchaleishvili, Vakhtang; Di Eusanio, Marco; Yan, Tristan D.; Phan, Kevin Background With improving technologies and an increasingly elderly populations, there have been an increasing number of therapeutic options available for patients requiring aortic valve replacement. Recent evidence suggests that transcatheter aortic valve implantation (TAVI) is one suitable option for high risk inoperable patients, as well as high risk operable patients. Sutureless valve technology has also been developed concurrently, with facilitates surgical aortic valve replacement (SUAVR) by allow resection and replacement of the native aortic valve with minimal sutures and prosthesis anchoring required. For patients amenable for both TAVI and SUAVR, the evidence is unclear with regards to the benefits and risks of either approach. The objectives are to compare the perioperative outcomes and intermediate-term survival rates of TAVI and SUAVR in matched or propensity score matched studies. Methods A systematic literature search was performed to include all matched or propensity score matched studies comparing SUAVR versus TAVI for severe aortic stenosis. A meta-analysis with odds ratios (OR) and mean differences were performed to compare key outcomes including paravalvular regurgitation and short and intermediate term mortality. Results Six studies met our inclusion criteria giving a total of 741 patients in both the SUAVR and TAVI arm of the study. Compared to TAVI, SUAVR had a lower incidence of paravalvular leak (OR =0.06; 95% CI: 0.03–0.12, P<0.01). There was no difference in perioperative mortality, however SUAVR patients had significantly better survival rates at 1 (OR =2.40; 95% CI: 1.40–4.11, P<0.01) and 2 years (OR =4.62; 95% CI: 2.62–8.12, P<0.01). Conclusions The present study supports the use of minimally invasive SUAVR as an alternative to TAVI in high risk patients requiring aortic replacement. The presented results require further validation in prospective, randomized controlled studies. PMID:28066608 Gotzmann, Michael; Czauderna, Anna; Hehnen, Tobias; Aweimer, Assem; Lind, Alexander; Kloppe, Axel; Bösche, Leif; Mügge, Andreas; Ewers, Aydan There is little known about the long-term results of the CoreValve prosthesis. The aim of this study was to assess the 3-year clinical and hemodynamic outcomes of the CoreValve prosthesis. One hundred fifty consecutive patients with severe aortic stenosis successfully underwent transcatheter aortic valve implantation (TAVI) with the CoreValve prosthesis. The primary study end point was death from any cause after TAVI. The secondary end points were defined as (1) cardiovascular death and (2) prosthesis-related mortality and morbidity. At 1 to 3 years, all-cause mortality rates were 25%, 32%, and 41%, respectively, and cardiovascular mortality rates were 14%, 21%, and 27%, respectively. Before TAVI, 95% of patients were in New York Heart Association class III or IV. Of the surviving patients, rates of New York Heart Association class III or IV at 1 to 3 years were 33%, 39%, and 38%, respectively. There was an annual decrease of the valve area of approximately 0.1 cm². Aortic restenosis occurred in 2 patients. Moderate or severe aortic regurgitation (AR) occurred in 15% of patients immediately after TAVI. Twenty patients (13%) had a slight worsening of AR within 3 years. New severe AR did not occur. The incidence of prosthesis-related endocarditis was 0.66% per year. Overall, 7 patients (incidence of 1.5% per year) had a clinically relevant problem of the prosthesis. In conclusion, TAVI with the CoreValve prosthesis had favorable effects on symptoms and outcomes even after 3 years. These results are clouded by side effects, such as AR and prosthesis-related mortality and morbidity. Baikoussis, Nikolaos G; Dedeilias, Panagiotis; Prappa, Efstathia; Argiriou, Michalis We would like to present in this paper a patient with severe aortic valve stenosis referred to our department for surgical aortic valve replacement. In this patient, it was intraoperatively detected an unexpected heavily calcified porcelain ascending aorta. We present the treatment options in this situation, the difficulties affronted intraoperatively, the significance of the preoperative chest computed tomography scan and the use of the Perceval S aortic valve as ideal bioprosthesis implantation. This is a self-expanding, self-anchoring, and sutureless valve with a wide indication in all patients requiring aortic bioprosthesis. Baikoussis, Nikolaos G; Dedeilias, Panagiotis; Prappa, Efstathia; Argiriou, Michalis We would like to present in this paper a patient with severe aortic valve stenosis referred to our department for surgical aortic valve replacement. In this patient, it was intraoperatively detected an unexpected heavily calcified porcelain ascending aorta. We present the treatment options in this situation, the difficulties affronted intraoperatively, the significance of the preoperative chest computed tomography scan and the use of the Perceval S aortic valve as ideal bioprosthesis implantation. This is a self-expanding, self-anchoring, and sutureless valve with a wide indication in all patients requiring aortic bioprosthesis. PMID:28074827 Spartalis, Michael; Tzatzaki, Eleni; Spartalis, Eleftherios; Damaskos, Christos; Moris, Demetrios; Tsiapras, Dimitrios; Voudris, Vassilis Quadricuspid aortic valve (QAV) is a rare congenital aortic valve abnormality. It is less common as compared to bicuspid or unicuspid aortic valve abnormality. QAV causes aortic regurgitation usually in the fifth to sixth decade of life. We present a rare case of a female patient with cryptogenic stroke due to a QAV and a patent foramen ovale (PFO). The patient underwent transcatheter closure of PFO, as there was no clear indication for surgery for her valve. Surgical removal remains the method of choice for the treatment of the QAV before left ventricular decompensation occurs. The presence of patent vein grafts on the proximal aorta may cause technical difficulties during reoperations for aortic valve replacement after previous coronary artery bypass surgery. A 65-year-old man underwent reoperation for aortic valve replacement two years after his first open heart surgery (valve-sparing aortic root replacement and aorta-right coronary artery saphenous vein graft). The aortotomy incision was started approximately 2 cm above the proximal anastomosis and continued down at both sides until the prosthetic graft. The reverse U aortotomy prevents unnecessary and risky manipulations of proximal anastomoses, provides perfect exposure, and can be used securely during reoperative aortic valve surgery. Von Der Emde, Jürgen; Eberlein, Ulrich; Breme, Jürgen From August 1971 through November 1972, we implanted 62 Model 2 DeBakey-Surgitool aortic valve prostheses in 62 patients, 4 of whom later had clinically asymptomatic strut fractures. In 1 case, the patient died suddenly, and autopsy revealed detachment of the ball-cage; in each of the other 3 cases, fractures of 2 struts close to the base of the prosthesis were diagnosed fluoroscopically, and the patients underwent successful reoperation. The interval between implantation and reoperation ranged from 11 months to 16 years, 9 months. In 1 patient, retrospective study of chest radiographs revealed that the fracture had been present for 2½ years. Larger valves (≥ A6) were affected significantly more often than smaller ones. We performed metallurgic analysis of 1 prosthesis: results revealed strut wear from fatigue cracking and secondary abrasion. Strut fracture was also promoted by suspension of the cage at right angles to the prosthetic ring and by use of a pyrolytic carbon ball in a titanium cage (i.e., an occluder harder than its holder). Patients with DeBakey-Surgitool aortic valve prostheses should undergo annual radiologic examinations to enable early detection of strut fractures. Prophylactic valve replacement is not indicated. (Texas Heart Institute Journal 1990;17:223-7) Images PMID:15227175 Leon, Martin B; Gada, Hemal; Fontana, Gregory P Transcatheter aortic valve replacement (TAVR) is a novel less-invasive therapy for high-risk patients with severe aortic stenosis (AS). Despite the impressive clinical growth of TAVR, there are many challenges as well as future opportunities. The heart valve team serves as the central vehicle for determining appropriate case selection. Considerations which impact clinical therapy decisions include frailty assessments and defining clinical "futility". There are many controversial procedural issues; choice of vascular access site, valve sizing, adjunctive imaging, and post-dilatation strategies. Complications associated with TAVR (strokes, vascular and bleeding events, para-valvular regurgitation, and conduction abnormalities) must be improved and will require procedural and/or technology enhancements. TAVR site training mandates a rigorous commitment to established society and sponsor guidelines. In the future, TAVR clinical indications should extend to bioprosthetic valve failure, intermediate risk patients, and other clinical scenarios, based upon well conducted clinical trials. New TAVR systems have been developed which should further optimize clinical outcomes, by reducing device profile, providing retrievable features, and preventing para-valvular regurgitation. Other accessory devices, such as cerebral protection to prevent strokes, are also being developed and evaluated in clinical studies. TAVR is a worthwhile addition to the armamentarium of therapies for patients with AS. Current limitations are important to recognize and future opportunities to improve clinical outcomes are being explored. Copyright © 2014 Elsevier Inc. All rights reserved. Zahn, Ralf; Schiele, Rudolf; Kilkowski, Caroline; Klein, Bärbel; Zeymer, Uwe; Werling, Christiane; Lehmann, Andreas; Gerckens, Ulrich; Saggau, Werner Transcatheter aortic valve implantation (TAVI) has been introduced for the treatment of severe symptomatic aortic stenosis in patients not suitable for surgical valve replacement. However, a potential problem of TAVI is the development of severe aortic insufficiency after valve implantation due to a too-low implantation of the valve. Since August 2008, a total of 33 TAVI procedures using the 18 Fr Medtronic CoreValve ReValving system has been performed at the authors' institution. Severe post-implantation aortic regurgitation occurred in three patients (9%), due to a too-low implantation. Two of these patients underwent a catheter-based repositioning of the valve using a standard snare; the third patient declined any further intervention. Both repositioning procedures were uneventful, with no significant residual regurgitation. Severe aortic regurgitation after TAVI with the Medtronic CoreValve system is not uncommon. If the valve is implanted too low, a catheter-based valve repositioning may be the method of choice to resolve the problem. Harolds, Jay A Initially, the transcatheter aortic valve replacement procedure was approved only for patients with aortic stenosis that was both severe and symptomatic who either also had too high a risk of aortic valve replacement surgery to have the surgery or who had a high risk for the surgery. Between the years 2012 and 2015, the death rate at 30 days declined from an initial rate of 7.5% to 4.6%. There has also been more use of the transfemoral approach over the years. In 2016, the transcatheter aortic valve replacement was approved for patients with aortic stenosis at intermediate risk of surgery. Reynolds, Matthew R; Lei, Yang; Wang, Kaijun; Chinnakondepalli, Khaja; Vilain, Katherine A; Magnuson, Elizabeth A; Galper, Benjamin Z; Meduri, Christopher U; Arnold, Suzanne V; Baron, Suzanne J; Reardon, Michael J; Adams, David H; Popma, Jeffrey J; Cohen, David J Previous studies of the cost-effectiveness of transcatheter aortic valve replacement (TAVR) have been based primarily on a single balloon-expandable system. The goal of this study was to evaluate the cost-effectiveness of TAVR with a self-expanding prosthesis compared with surgical aortic valve replacement (SAVR) for patients with severe aortic stenosis and high surgical risk. We performed a formal economic analysis on the basis of individual, patient-level data from the CoreValve U.S. High Risk Pivotal Trial. Empirical data regarding survival and quality of life over 2 years, and medical resource use and hospital costs through 12 months were used to project life expectancy, quality-adjusted life expectancy, and lifetime medical costs in order to estimate the incremental cost-effectiveness of TAVR versus SAVR from a U.S. Relative to SAVR, TAVR reduced initial length of stay an average of 4.4 days, decreased the need for rehabilitation services at discharge, and resulted in superior 1-month quality of life. Index admission and projected lifetime costs were higher with TAVR than with SAVR (differences $11,260 and $17,849 per patient, respectively), whereas TAVR was projected to provide a lifetime gain of 0.32 quality-adjusted life-years ([QALY]; 0.41 LY) with 3% discounting. Lifetime incremental cost-effectiveness ratios were $55,090 per QALY gained and $43,114 per LY gained. Sensitivity analyses indicated that a reduction in the initial cost of TAVR by ∼$1,650 would lead to an incremental cost-effectiveness ratio <$50,000/QALY gained. In a high-risk clinical trial population, TAVR with a self-expanding prosthesis provided meaningful clinical benefits compared with SAVR, with incremental costs considered acceptable by current U.S. With expected modest reductions in the cost of index TAVR admissions, the value of TAVR compared with SAVR in this patient population would become high. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Kamal, Muhammad Umar; Riaz, Irbaz Bin; Smith, M Cristy Summary In intravenous drug abusers, infective endocarditis usually involves right-sided valves, with Staphylococcus aureus being the most common etiologic agent. We present a patient who is an intravenous drug abuser with left-sided (aortic valve) endocarditis caused by Enterococcus faecalis who subsequently developed an anterior mitral valve aneurysm, which is an exceedingly rare complication. A systematic literature search was conducted which identified only five reported cases in the literature of mitral valve aneurysmal rupture in the setting of E. faecalis endocarditis. Real-time 3D-transesophageal echocardiography was critical in making an accurate diagnosis leading to timely intervention. Learning objectives Early recognition of a mitral valve aneurysm (MVA) is important because it may rupture and produce catastrophic mitral regurgitation (MR) in an already seriously ill patient requiring emergency surgery, or it may be overlooked at the time of aortic valve replacement (AVR). Real-time 3D-transesophageal echocardiography (RT-3DTEE) is much more advanced and accurate than transthoracic echocardiography for the diagnosis and management of MVA. PMID:27249815 Ussia, Gian Paolo; Barbanti, Marco; Immè, Sebastiano; Scarabelli, Marilena; Mulè, Massimiliano; Cammalleri, Valeria; Aruta, Patrizia; Pistritto, Anna Maria; Capodanno, Davide; Deste, Wanda; Di Pasqua, Maria Concetta; Tamburino, Corrado Transcatheter aortic valve implantation (TAVI) is an emerging alternative to palliative medical therapy for nonsurgical patients with severe aortic stenosis. There is a paucity of detailed data on the management and outcome of complications related to the sub-optimal deployment of the prosthesis. We appraised the incidence and management of early implant failure occurring during TAVI. Of 110 patients who underwent TAVI using the third generation 18-French CoreValve ReValving System (Medtronic, MN) in our Institution between June 2007 and January 2010, we identified those experiencing early implant failure and reported on their management and clinical outcome. The primary endpoint was the incidence of major adverse cardiovascular and cerebrovascular event (MACCE) at 30 days and mid-term follow up. Early implant failure occurred in 18 of 110 patients (16.3%). The most common cause was prosthesis under-expansion conditioning moderate to severe peri-valvular leak (44.4%). Prosthesis deployment too low or too high with respect to the aortic annulus leading to severe peri-valvular leak occurred in 22.2% and 5.5% of patients, respectively. Need of valve retrieve after the first attempt of deployment occurred in four cases (22.2%). Prosthesis embolization in the ascending aorta occurred in 5.5% of patients who experienced early implant failure. All implant failure cases were managed percutaneously with gain in aortic valve area from 0.44 ± 0.17 to 1.28 ± 0.27 cm(2) (P < 0.001), decrease of mean transaortic gradient from 55.00 ± 19.51 to 11.58 ± 5.91 mmHg (P < 0.001) and no MACCE at 30 days. After 11 ± 6 months, MACCE occurred cumulatively in two patients (11.1%). Early implant failure can complicate the TAVI procedure with the CoreValve system, but it can be managed safely and effectively with bailout transcatheter techniques, avoiding surgery, with good early and mid-term clinical and echocardiographic results. Sullivan, M F; Roberts, W C Clinical and morphologic observations are described in 12 patients who underwent simultaneous replacement of the tricuspid, mitral and aortic valves. All 12 patients had mitral stenosis, 10 aortic valve stenosis and 2 pure aortic valve regurgitation; 5 had tricuspid valve stenosis and 7 pure tricuspid valve regurgitation. Of the 10 patients who died within 60 days of triple valve replacement, 7 had the low cardiac output syndrome, which in 4, and possibly 5, of the 7 was attributed to prosthetic aortic valve stenosis. In none of the 12 patients was the ascending aorta dilated, and in the 4 (possibly 5) patients with low cardiac output, the space between the surface of the caged poppet (4 patients) or margins of the tilting disc (1 patient) in the aortic valve position and the aortic endothelium appeared inadequate to allow unobstructed flow despite small-sized prostheses in all but 1 patient. Thus, aortic valve replacement in the setting of triple valve dysfunction is hazardous or potentially so. The relative small sizes of the hearts in these patients also make valve replacement more difficult (and hazardous) compared to hearts with larger ventricles and aortas. Spargias, Konstantinos; Bouboulis, Nikolaos; Halapas, Antonios; Chrissoheris, Michael; Skardoutsos, Spyridon; Nikolaou, Joulia; Tsolakis, Apostolos; Mourmouris, Christos; Pattakos, Stratis Transcatheter aortic valve replacement (TAVR) is now an established treatment for certain patients with severe aortic valve stenosis (AS). However, as the number of patients screened for TAVR increases, many are found to have absolutely no option for peripheral artery access. Transaortic valve replacement (TAoVR) has been proposed as a new alternative route in patients deemed unsuitable for conventional approaches. We present our first series of TAoVR cases using the Edwards Sapien-XT and the Medtronic CoreValve prostheses. Twenty-five (25) symptomatic patients (mean age 78 ± 8 years, mean logistic EuroSCORE I 25 ± 11%) with severe AS underwent TAoVR using the Sapien-XT valve (10 patients) or the CoreValve (15 patients). The mean fluoroscopy time was 15.6 ± 4.2 minutes, the mean time in the intensive care unit was 1.9 ± 1.0 days, and the mean hospital stay was 6.4 ± 1.6 days. The mean effective aortic valve area increased (from 0.68 ± 0.15 cm(2) to 1.82 ± 0.34 cm(2), p<0.001) and the mean transvalvular pressure gradient declined (from 48 ± 15 mmHg to 9 ± 5 mmHg, p<0.05) post implantation. The procedural mortality was 0% and the in-hospital mortality was 4% (one death at day 3 due to cardiogenic shock). The mean NYHA functional class improved from 3.2 ± 0.4 to 1.5 ± 0.9 at 30 days. Our initial experience with the TAoVR approach using both the Edwards Sapien-XT and the Medtronic CoreValve prosthesis demonstrated that it could be performed safely, resulting in substantial acute echocardiographic and early clinical improvement. Langer, Nathaniel B; Hamid, Nadira B; Nazif, Tamim M; Khalique, Omar K; Vahl, Torsten P; White, Jonathon; Terre, Juan; Hastings, Ramin; Leung, Diana; Hahn, Rebecca T; Leon, Martin; Kodali, Susheel; George, Isaac The experience with transcatheter aortic valve replacement is increasing worldwide; however, the incidence of potentially catastrophic cardiac or aortic complications has not decreased. In most cases, significant injuries to the aorta, aortic valve annulus, and left ventricle require open surgical repair. However, the transcatheter aortic valve replacement patient presents a unique challenge as many patients are at high or prohibitive surgical risk and, therefore, an open surgical procedure may not be feasible or appropriate. Consequently, prevention of these potentially catastrophic injuries is vital, and practitioners need to understand when open surgical repair is required and when alternative management strategies can be used. The goal of this article is to provide an overview of current management and prevention strategies for major complications involving the aorta, aortic valve annulus, and left ventricle. Danielecki, Cezary; Bugajski, Paweł; Olszewski, Roman; Greberski, Krzysztof; Kalawski, Ryszard The patient was admitted to the Department of Cardiac Surgery of the J. Struś City Hospital in Poznan due to infective endocarditis involving the aortic, mitral, and tricuspid valves. Implantation of three biological valve prostheses proceeded without complications. Starting on day 23, the patient's general condition deteriorated, with high fever. Despite postoperative antibiotic therapy, transesophageal echocardiography revealed the presence of vegetation on the bioprosthetic aortic valve. On the 46(th) day after the initial surgery, the patient required replacement of the aortic bioprosthesis, which exhibited the presence of numerous vegetations. The bioprosthetic mitral and tricuspid valves were not affected by the degenerative process. On the 12(th) day after the reimplantation of the bioprosthetic aortic valve, the patient was discharged from the hospital in good general condition. Bugajski, Paweł; Olszewski, Roman; Greberski, Krzysztof; Kalawski, Ryszard The patient was admitted to the Department of Cardiac Surgery of the J. Struś City Hospital in Poznan due to infective endocarditis involving the aortic, mitral, and tricuspid valves. Implantation of three biological valve prostheses proceeded without complications. Starting on day 23, the patient's general condition deteriorated, with high fever. Despite postoperative antibiotic therapy, transesophageal echocardiography revealed the presence of vegetation on the bioprosthetic aortic valve. On the 46th day after the initial surgery, the patient required replacement of the aortic bioprosthesis, which exhibited the presence of numerous vegetations. The bioprosthetic mitral and tricuspid valves were not affected by the degenerative process. On the 12th day after the reimplantation of the bioprosthetic aortic valve, the patient was discharged from the hospital in good general condition. PMID:27785140 Seitz, W; Oppenheimer, L; McIlroy, M; Nelson, D; Operschall, J An orifice equation is derived relating the effective aortic valve area, A, the average aortic valve pressure gradient, dP, the stroke volume, SV, and the heart frequency, FH, through considerations of momentum conservation across the aortic valve. This leads to a formula consistent with Newton's second law of motion. The form of the new equation is A = (7.5 X 10(-5)) SV FH2/Pd, where A, VS, FH and Pd are expressed in cm2, ml, s-1 and mmHg, respectively. Aortic valve areas computed with the new orifice equation are found to correlate with those computed by the Gorlin formula in conditions of resting haemodynamic states at a level of r = 0.86, SE = 0.25 cm2, N = 120. The results suggest that the new formula may be considered as an independent orifice equation having a similar domain of validity as the Gorlin formula. The new equation offers the possibility of deriving additional useful haemodynamic relationships through combination with established cardiological formulas and applying it in a noninvasive Doppler ultrasonic or echocardiographic context. Collins, Jeremy D; Semaan, Edouard; Barker, Alex; McCarthy, Patrick; Carr, James C; Markl, Michael; Malaisrie, S. Chris Background The purpose is to compare aortic hemodynamics and blood flow patterns using in-vivo 4D flow MRI in patients following valve-sparing aortic root replacement (VSARR) and aortic root replacement with bio-prosthetic valves (BIO-ARR). Methods In-vivo 4D flow MRI was performed in 11 patients after VSARR (47±18 years, 6 BAV, 5 TAV), 16 patients after BIO-ARR (52±14 years), and 10 healthy controls (47±16 years). Analysis included 3D blood flow visualization and grading of helix flow in the ascending aorta (AAo) and arch. Peak systolic velocity was quantified in 9 analysis planes in the AAo, aortic arch, and descending aorta. Flow profile uniformity was evaluated in the aortic root and ascending aorta. Results Peak systolic velocity (2.0–2.5m/s) in the aortic root and AAo in both VSARR and BIO-ARR were elevated compared to controls (1.1–1.3m/s, p < 0.005). Flow asymmetry in BIO-ARR was increased compared to VSARR, evidenced by more AAo outflow jets (9 of 16 BIO-ARR, 0 of 11 in VSARR). BIO-ARR exhibited significantly (p<0.001) increased helix flow in the AAo as a measure of increased flow derangement. Finally, peak systolic velocities were elevated at the aortic root for BIO-ARR (2.5 vs 2.0m/s, p < 0.05) but lower in the distal AAo when compared to VSARR.. Conclusion VSARR results in improved hemodynamic outcomes when compared with BIO-ARR as indicated by reduced peak velocities in the aortic root and less helix flow in the AAo by 4D flow MRI. Longitudinal research assessing the clinical impact of these differences in hemodynamic outcomes is warranted. PMID:26212514 Bortolotti, Uberto; Celiento, Michele; Milano, Aldo D The main goal of aortic valve replacement (AVR) is to obtain relief from the fixed left ventricular (LV) obstruction by replacing the aortic valve with a prosthesis, either mechanical or biological, of adequate size. Most currently available prostheses provide satisfactory hemodynamic performance, but small-sized prostheses may be associated with high transvalvular gradients and suboptimal effective orifice area that result in prosthesis-patient mismatch (PPM), and thus are far from ideal for use in young, active patients. The avoidance of PPM is advisable as it has been repeatedly associated with increased mortality, decreased exercise tolerance and an impaired regression of LV hypertrophy after AVR for severe aortic stenosis. Enlargement of the aortic annulus (EAA) has proved to be a valuable method to prevent PPM in the presence of a diminutive aortic root. This review outlines the various techniques described for EAA, presenting technical details, long-term results and major procedure-related complications, and discussing the current role of EAA in patients requiring AVR. Pichamuthu, Joseph E; Phillippi, Julie A; Cleary, Deborah A; Chew, Douglas W; Hempel, John; Vorp, David A; Gleason, Thomas G Ascending thoracic aortic aneurysm (ATAA) predisposes patients to aortic dissection and has been associated with diminished tensile strength and disruption of collagen. Ascending thoracic aortic aneurysms arising in patients with bicuspid aortic valve (BAV) develop earlier than in those with tricuspid aortic valves (TAV) and have a different risk of dissection. The purpose of this study was to compare aortic wall tensile strength between BAV and TAV ATAAs and determine whether the collagen content of the ATAA wall is associated with tensile strength and valve phenotype. Longitudinally and circumferentially oriented strips of ATAA tissue obtained during elective surgery were stretched to failure, and collagen content was estimated by hydroxyproline assay. Experimental stress-strain data were analyzed for failure strength and elastic mechanical variables: α, β, and maximal tangential stiffness. The circumferential and longitudinal tensile strengths were higher for BAV ATAAs when compared with TAV ATAAs. The α and β were lower for BAV ATAAs when compared with TAV ATAAs. The maximal tangential stiffness was higher for circumferential when compared with longitudinal orientation in both BAV and TAV ATAAs. The amount of hydroxyproline was equivalent in BAV and TAV ATAA specimens. Although there was a moderate correlation between the collagen content and tensile strength for TAV, this correlation is not present in BAV. The increased tensile strength and decreased values of α and β in BAV ATAAs despite uniform collagen content between groups indicate that microstructural changes in collagen contribute to BAV-associated aortopathy. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved. Kirmani, Bilal H; Jones, Sion G; Malaisrie, S C; Chung, Darryl A; Williams, Richard Jnn Aortic valve disease is a common condition that is easily treatable with cardiac surgery. This is conventionally performed by opening the sternum longitudinally down the centre ("median sternotomy") and replacing the valve under cardiopulmonary bypass. Median sternotomy is generally well tolerated, but as less invasive options have become available, the efficacy of limited incisions has been called into question. In particular, the effects of reducing the visibility and surgical access has raised safety concerns with regards to the placement of cannulae, venting of the heart, epicardial wire placement, and de-airing of the heart at the end of the procedure. These difficulties may increase operating times, affecting outcome. The benefits of smaller incisions are thought to include decreased pain; improved respiratory mechanics; reductions in wound infections, bleeding, and need for transfusion; shorter intensive care stay; better cosmesis; and a quicker return to normal activity. To assess the effects of minimally invasive aortic valve replacement via a limited sternotomy versus conventional aortic valve replacement via median sternotomy in people with aortic valve disease requiring surgical replacement. We performed searches of CENTRAL, MEDLINE, Embase, clinical trials registries, and manufacturers' websites from inception to July 2016, with no language limitations. We reviewed references of identified papers to identify any further studies of relevance. Randomised controlled trials comparing aortic valve replacement via a median sternotomy versus aortic valve replacement via a limited sternotomy. We excluded trials that performed other minimally invasive incisions such as mini-thoracotomies, port access, trans-apical, trans-femoral or robotic procedures. Although some well-conducted prospective and retrospective case-control and cohort studies exist, these were not included in this review. Two review authors independently assessed trial papers to extract data Bianchi, Matteo; Ghosh, Ram P; Marom, Gil; Slepian, Marvin J; Bluestein, Danny Calcific aortic valve disease (CAVD) is a cardiovascular condition that causes the progressive narrowing of the aortic valve (AV) opening, due to the growth of bone-like deposits all over the aortic root (AR). Transcatheter aortic valve replacement (TAVR), a minimally invasive procedure, has recently become the only lifesaving solution for patients that cannot tolerate the standard surgical valve replacement. However, adverse effects, such as AR injury or paravalvular leakage (PVL), may occur as a consequence of a sub-optimal procedure, due to the presence of calcifications in situ. Additionally, the crimping required for delivering the valve via stenting may damage the valve. The aim of the present study is to comparatively assess the crimping mechanics of the commercialized Edwards SAPIEN valve and an alternative polymeric valve (Polynova, Inc) and to evaluate the effect of different TAVR deployment positions using patient-specific numerical models. The optimal deployment location for achieving better patient outcomes was calculated and based on the interactions between the TAVR stent and the native AR. Results demonstrated that the Polynova valve withstands the crimping process better than the SAPIEN valve. Furthermore, deployment simulations showed the role that calcifications deposits may play in the TAVR sub-optimal valve anchoring to the AV wall, leading to the presence of gaps that result in PVL. Okamoto, Y; Sakakibara, K; Inoue, H; Suzuki, S; Shindo, S; Matsumoto, M We report a case of aortic valve replacement and hemiarch replacement with reconstruction of the brachiocephalic artery in a patient with a porcelain aorta. A 65-year-old man was admitted to the hospital for aortic stenosis. Computed tomography demonstrated severe aortic calcification and extensive calcification covering a wide area of the aorta. The echocardiography showed a highly calcified aortic valve and a pressure gradient of 109 mmHg across the aortic valve. At surgery, calcification of the ascending aorta was severe and involved its entire circumference. Therefore, 2 cannulae were inserted to the right axillary and right femoral arteries for extracorporeal circulation. We performed replacement of the ascending aorta and hemiarch with reconstruction of the brachiocephalic artery under circulatory arrest and antegrade cerebral perfusion, as well as aortic valve replacement with a 21 mm St. Jude Medical mechanical valve. He had no major cardiac complications during the postoperative course, and was discharged on postoperative day 33. Albes, Johannes M; Stock, Ulrich A; Hartrumpf, Martin Restitution strategies of the insufficient aortic valve belong to the clinical armamentarium. To date, the accumulated body of evidence comprises 126 articles dealing with restitution strategies on the insufficient aortic valve with concomitant aortic surgery. In a cumulative analysis an almost identical number of reimplantation (506) and remodeling (489) procedures were found in the literature, whereas 357 patients underwent aortic valve resuspension. The cumulative results tend to favor the reimplantation technique in terms of longevity of the reconstruction, particularly in congenital degenerative disorders of the aortic wall, whereas remodeling appears to exhibit a more physiologic behavior of the reconstructed valve and re-suspension serves as a simplified approach particularly in acute type A dissection. Although restitution of the native aortic valve has its place in current treatment options, the accumulated worldwide numbers indicate that it is not yet routinely implemented in the vast majority of cardiac institutions. Carlson, Misty; Airhart, Nathan; Lopez, Leo; Silberbach, Michael Girls and women with Turner syndrome are at risk for aortic dissection and rupture. However, the size of the aorta and the clinical characteristics among those with Turner syndrome and dissection have received little attention. We obtained medical records from 20 individuals who voluntarily participated in the International Turner Syndrome Aortic Dissection Registry. Type A dissections occurred in 17 of 20 (85%) cases, and type B occurred in 3 cases of which 1 occurred after coarctation stent placement. Of those with spontaneous aortic dissections, 18 of 19 (95%) had an associated cardiac malformation that included a bicuspid aortic valve. In 1 individual there was no predisposing finding other than the presence of Turner syndrome. Associated pregnancy was documented in 1 of 19 (5%). More than half (13/19, 68%) came to medical attention >24 hours after the onset of symptoms. For those with type A dissections, the mean ascending aortic size index was 2.7±0.6 cm/m(2) (n=9). Aortic dissection in Turner syndrome occurs in young individuals at smaller aortic diameters than in the general population or other forms of genetically triggered aortopathy. The absence of aortic valve or other cardiac malformations appears to markedly reduce the risk of aortic dissection However, aortic dissection can occur in Turner syndrome without cardiac malformations or hypertension. Individuals with Turner syndrome who are >18 years of age with an ascending aortic size index >2.5 cm/m(2) should be considered for an aortic operation to prevent aortic dissection. Alkhouli, Mohamad; Melito, Betsy; Ling, Frederick S The development of de novo aortic insufficiency (AI) is a significant complication of long-term LVAD support, which can lead to ineffective support, decreased device durability, end organ malperfusion, and increased mortality. Surgical aortic valve (AV) closure has been the standard treatment for symptomatic patients, but is associated with high mortality and recurrence of AI. Percutaneous AV closure using the Amplatzer cribriform device is a feasible and may be the preferable option to treat LVAD-associated severe AI in high-surgical risk patients. Certain technical issues with this procedure should be taken into consideration to achieve optimal results. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc. Leon, Martin B; Smith, Craig R; Mack, Michael; Miller, D Craig; Moses, Jeffrey W; Svensson, Lars G; Tuzcu, E Murat; Webb, John G; Fontana, Gregory P; Makkar, Raj R; Brown, David L; Block, Peter C; Guyton, Robert A; Pichard, Augusto D; Bavaria, Joseph E; Herrmann, Howard C; Douglas, Pamela S; Petersen, John L; Akin, Jodi J; Anderson, William N; Wang, Duolao; Pocock, Stuart Many patients with severe aortic stenosis and coexisting conditions are not candidates for surgical replacement of the aortic valve. Recently, transcatheter aortic-valve implantation (TAVI) has been suggested as a less invasive treatment for high-risk patients with aortic stenosis. We randomly assigned patients with severe aortic stenosis, whom surgeons considered not to be suitable candidates for surgery, to standard therapy (including balloon aortic valvuloplasty) or transfemoral transcatheter implantation of a balloon-expandable bovine pericardial valve. The primary end point was the rate of death from any cause. A total of 358 patients with aortic stenosis who were not considered to be suitable candidates for surgery underwent randomization at 21 centers (17 in the United States). At 1 year, the rate of death from any cause (Kaplan–Meier analysis) was 30.7% with TAVI, as compared with 50.7% with standard therapy (hazard ratio with TAVI, 0.55; 95% confidence interval [CI], 0.40 to 0.74; P<0.001). The rate of the composite end point of death from any cause or repeat hospitalization was 42.5% with TAVI as compared with 71.6% with standard therapy (hazard ratio, 0.46; 95% CI, 0.35 to 0.59; P<0.001). Among survivors at 1 year, the rate of cardiac symptoms (New York Heart Association class III or IV) was lower among patients who had undergone TAVI than among those who had received standard therapy (25.2% vs. 58.0%, P<0.001). At 30 days, TAVI, as compared with standard therapy, was associated with a higher incidence of major strokes (5.0% vs. 1.1%, P=0.06) and major vascular complications (16.2% vs. 1.1%, P<0.001). In the year after TAVI, there was no deterioration in the functioning of the bioprosthetic valve, as assessed by evidence of stenosis or regurgitation on an echocardiogram. In patients with severe aortic stenosis who were not suitable candidates for surgery, TAVI, as compared with standard therapy, significantly reduced the rates of death from any cause De Palma, Rodney; Saleh, Nawsad; Ruck, Andreas; Settergren, Magnus Percutaneous valve implantation is a recognized therapy for calcific aortic stenosis in those patients who are inoperable or at high surgical risk. The transfemoral approach is the most frequently used method for device delivery, but a tortuous calcific aorta and the inflexibility of large-caliber endovascular equipment can impede progress or even cause the procedure to be abandoned. Herein, the use of a technique employing a snare to safely overcome device obstruction in the aortic arch of an elderly female patient is described. The technique may be of practical value whenever any large-caliber device is obstructed in the circulation. Berry, Colin; Oukerraj, Latifa; Asgar, Anita; Lamarche, Yoan; Marcheix, Bertrand; Denault, André Y; Laborde, Jean-Claude; Cartier, Raymond; Ducharme, Anique; Bonan, Raoul; Basmadjian, Arsène J Percutaneous aortic valve replacement (PAVR) is an emerging therapy for nonsurgical patients with severe aortic stenosis (AS). We examined the role of transesophageal echocardiography (TEE) in PAVR. TEE was used initially to assess the native valve and aortic root, and served as a guide during PAVR. Following prosthetic valve deployment, TEE was used to assess valve function. Eleven patients aged 82 +/- 10 years with NYHA III-IV underwent PAVR. Periprocedural TEE gave immediate information on prosthetic position and function, LV function, mitral regurgitation, pericardium, and thoracic aorta anatomy. There was excellent visual agreement between fluoroscopic and TEE images of prosthetic positioning and deployment. TEE facilitated the detection and management of procedure-related complications. Compared with pre-PAVR, AV area (0.56 +/- 0.19 cm(2) vs. 1.3 +/- 0.4 cm(2); P < 0.001) and LVEF (49 +/- 17% vs. 56 +/- 11%; P < 0.001) increased. TEE provides key anatomical and functional information, and serves as a diagnostic guide for complications, which may arise during PAVR. Ferreira, Renata Tosoni Rodrigues; Silva, Roberto Rocha e; Marchi, Evaldo Objective To compare the results of aortic valve replacement with access by sternotomy or minimally invasive approach. Methods Retrospective analysis of medical records of 37 patients undergoing aortic valve replacement by sternotomy or minimally invasive approach, with emphasis on the comparison of time of cardiopulmonary bypass and aortic clamping, volume of surgical bleeding, time of mechanical ventilation, need for blood transfusion, incidence of atrial fibrillation, length of stay in intensive care unit, time of hospital discharge, short-term mortality and presence of surgical wound infection. Results Sternotomy was used in 22 patients and minimally invasive surgery in 15 patients. The minimally invasive approach had significantly higher time values of cardiopulmonary bypass (114.3±23.9 versus 86.7±19.8min.; P=0.003), aortic clamping (87.4±19.2 versus 61.4±12.9 min.; P<0.001) and mechanical ventilation (287.3±138.9 versus 153.9±118.6 min.; P=0.003). No difference was found in outcomes surgical bleeding volume, need for blood transfusion, incidence of atrial fibrillation, length of stay in intensive care unit and time of hospital discharge. No cases of short-term mortality or surgical wound infection were documented. Conclusion The less invasive approach presented with longer times of cardiopulmonary bypass, aortic clamping and mechanical ventilation than sternotomy, however without prejudice to the length of stay in intensive care unit, time of hospital discharge and morbidity. PMID:28076618 Mueller, X M; Tevaearai, H T; Genton, C Y; Hurni, M; Ruchat, P; Fischer, A P; Stumpe, F; von Segesser, L K Aortoplasty has been advocated for moderate dilatation of the ascending aorta associated with aortic valve disease. We report our results with this conservative approach. Seventeen consecutive patients with unsupported aortoplasty were reviewed. Twelve patients had aortic valve regurgitation and 5 had stenosis. The aortic wall was analyzed histologically in 14 patients. Follow-up was complete, with a mean time of 6 years (range, 2.3 to 10.5 years). Two patients among the 15 hospital survivors died during follow-up of causes unrelated to aortic pathology. Survival at 7 years was 86.7% (+/- 8.8%). Recurring aortic aneurysms developed in 4 patients after a mean time of 63 months, with an event-free survival at 7 years of 41% (+/- 21%). All of these 4 patients had aortic valve regurgitation and cystic medial necrosis. The recurrence rate of aneurysms after unsupported aortoplasty and aortic valve replacement is high in patients with aortic regurgitation. This strongly suggests that in these patients, the aortic dilatation is related to an underlying wall deficiency, associated with the aortic valve pathology, rather than to the hemodynamic stress imposed by the aortic valve disease. Jung, Yochun; Ahn, Byoung Hee; Lee, Kyo Seon; Jeong, In Seok; Kim, Kye Hun; Na, Kook Joo; Ryu, Sang-Wan; Oh, Sang Gi Prosthetic valve dehiscence after aortic valve surgery in Behçet's disease patients is common. We aimed to validate the usefulness of our new technique 'subannular endomyocardial implantation of valve prosthesis' designed to prevent prosthetic valve dehiscence. Subannular endomyocardial implantation of valve prosthesis involves suturing the sewing cuff of the valve prosthesis in the endomyocardium below the aortic annulus, which is based on the idea that annular tissue should be excluded from the suture line in Behçet's disease patients. Medical records of 7 patients in whom the new technique was performed between 2002 and 2014 were reviewed. Five men and two women were included (median age, 44 years). Aortic root replacement was performed in 6 cases, and aortic valve replacement in 1. No operative mortality occurred. Postoperatively, complete atrioventricular block developed in 3 cases, and permanent pacemakers were implanted in 2. No reoperation was performed for prosthetic valve dehiscence during the median 7.8-year follow-up. One late death occurred due to sudden cardiac arrest 8.4 years after surgery. One additional permanent pacemaker was implanted for complete atrioventricular block, which developed at 4.2 years postoperatively. The last echocardiography (median, 6.7 years after surgery) revealed no paravalvular leakages. Subannular endomyocardial implantation of valve prosthesis seems useful for preventing prosthetic valve dehiscence after aortic valve surgery for Behçet's disease. It poses a risk of complete atrioventricular block, but considering the high reoperation rate and mortality due to prosthetic valve dehiscence after conventional aortic valve surgery, this risk seems reasonable. Jilaihawi, Hasan; Chin, Derek; Spyt, Tomasz; Jeilan, Mohamed; Vasa-Nicotera, Mariuca; Mohamed, Noor; Bence, Johan; Logtens, Elaine; Kovac, Jan We sought to determine the significance of incomplete stent frame expansion after transcatheter aortic valve implantation with the Medtronic-CoreValve device. Incomplete coronary stent expansion is a well-described phenomenon. Transcatheter valves are mounted on stents; however, the incidence of incomplete stent expansion after transcatheter aortic valve implantation, its sequelae and predictors are poorly elucidated. The 18Fr CoreValve revalving system was used to treat anatomically and clinically suitable patients with severe calcific aortic stenosis. The postdeployment stent dimensions were measured on fluoroscopic images at multiple levels of the stent frame. Incomplete expansion at each was defined as <100% expected and complete expansion as ≥100%. These parameters were correlated to the hemodynamic and clinical end points. A total of 50 consecutive patients underwent transcatheter aortic valve implantation with the Medtronic-CoreValve at a single center from January 2007 to December 2008. For the inflow portion, incomplete expansion was seen in 54% of patients and was unrelated to the aortic valve area, peak or mean aortic valve gradients, or measures of aortic regurgitation, although it was paradoxically associated with a lower incidence of prosthesis-patient mismatch. Incomplete expansion of the constrained portion was seen in 62% of the patients and displayed a trend toward a greater incidence of aortic regurgitation grade 2 or greater, although this was rare. Incomplete expansion of the Medtronic CoreValve stent frame is common. For the most part, valvular hemodynamic function was satisfactory, regardless of the degree of expansion of the stent frame that carries it and a strategy of reluctant postdilation in the context of incomplete stent frame expansion was supported. Copyright © 2011 Elsevier Inc. All rights reserved. Akpinar, B; Sanisoğlu, I; Konuralp, C; Akay, H; Güden, M; Sönmez, B Over the years, many surgical methods have evolved for the treatment of ascending aortic aneurysm in combination with aortic valve regurgitation; however, precise guidelines for optimal surgical techniques for varying presentations have not been defined. We describe the use of a stentless porcine bioprosthesis (Medtronic Freestyle) in a patient with an ascending aortic aneurysm and aortic regurgitation. We used the complete root replacement method, and anastomosed a Dacron graft (Hemashield) between the bioprosthetic valve and the native aorta to replace the distal part of the aneurysm. Images PMID:10524742 Barnhart, Glenn R.; Shrestha, Malakh Lal Abstract Aortic stenosis is the most common valvular heart disease in the Western world. It is caused primarily by age-related degeneration and progressive calcification typically detected in patients 65 years and older. In patients presenting with symptoms of heart failure, the average survival rate is only 2 years without appropriate treatment. Approximately one half of all patients die within the first 2 to 3 years of symptom onset. In addition, the age of the patients presenting for aortic valve replacement (AVR) is increased along with the demographic changes. The Society of Thoracic Surgeons (STS) database shows that the number of patients older than 80 years has increased from 12% to 24% during the past 20 years. At the same time, the percentage of candidates requiring AVR as well as concomitant coronary bypass surgery has increased from 5% to 25%. Surgical AVR continues to be the criterion standard for treatment of aortic stenosis, improving survival and quality of life. Recent advances in prosthetic valve technology, such as transcatheter AVR, have expanded the indication for AVR to the extreme high-risk population, and the most recent surgical innovation, rapid deployment AVR, provides an additional tool to the surgeons’ armamentarium. PMID:26918310 Arsalan, Mani; Walther, Thomas Transcatheter aortic valve implantation (TAVI) has become the standard of care for inoperable patients, and the preferred treatment option for high-risk patients with severe aortic stenosis. Given that this therapy was intended for elderly patients with limited life expectancy, long-term durability has not been in the focus. Now that TAVI is increasingly being used in patients with intermediate-risk and lower-risk profiles, device durability has gained importance. The available mid-term results for TAVI are promising; however, little is known about the fate of TAVI devices beyond 5 years. The experience with long-term durability of surgical valves shows that ≥10-year follow-up is required to ensure reliable durability data. In this Review, we discuss the existing studies of TAVI durability, highlight differences between surgical and transcatheter treatment of aortic stenosis that might influence durability, and present a clinical solution for failed prostheses. Furthermore, we suggest how device durability might influence the future selection of patients for TAVI. Minale, C; Reifschneider, H J; Schmitz, E; Uckmann, F P The method of replacing the aortic valve via a minithoracotomy has been reported in the recent literature. Although this strategy has clear advantages, further refinements of the process make the procedure even less invasive. Aortic valve replacement was performed in 27 patients via a right parasternal minithoracotomy without rib resection. Cardiopulmonary bypass was connected through the same access site. Standard surgical technique and equipment were employed. There were no intraoperative complications. All patients survived and could be discharged home within 1 week, except 1. Cardiopulmonary bypass time, aortic cross-clamp time, and total operating time averaged 114 +/- 26, 76 +/- 19, and 190 +/- 40 minutes, respectively. Three patients could be extubated in the operative theater, the others in the intensive care unit at an average of 10 +/- 7 hours postoperatively. Chest drainage lost averaged 430 +/- 380 mL. The advantages of this method include further reduction of surgical trauma, early mobilization, and rehabilitation of the patient. Surgical technical improvements include avoidance of groin cannulation, simpler equipment, safe venting of the left ventricle, and preservation of chest wall integrity. Lang, Pencilla; Rajchl, Martin; McLeod, A. Jonathan; Chu, Michael W.; Peters, Terry M. Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to open-heart surgery, and is critically dependent on imaging for accurate placement of the new valve. Augmented image-guidance for TAVI can be provided by registering together intra-operative transesophageal echo (TEE) ultrasound and a model derived from pre-operative CT. Automatic contour delineation on TEE images of the aortic root is required for real-time registration. This study develops an algorithm to automatically extract contours on simultaneous cross-plane short-axis and long-axis (XPlane) TEE views, and register these features to a 3D pre-operative model. A continuous max-flow approach is used to segment the aortic root, followed by analysis of curvature to select appropriate contours for use in registration. Results demonstrate a mean contour boundary distance error of 1.3 and 2.8mm for the short and long-axis views respectively, and a mean target registration error of 5.9mm. Real-time image guidance has the potential to increase accuracy and reduce complications in TAVI. Onishi, S; Handa, S; Ikeda, F; Hosokawa, M; Yoshino, H; Ogawa, S; Nakamura, Y; Soma, Y; Inoue, T Serial echocardiographic analyses of the left ventricle (LV) were performed in 61 patients with aortic regurgitation before, one-six months, and six years after aortic valve replacement (AVR). There was no significant difference in the preoperative hemodynamic and echocardiographic data between 54 survivors and six deceased patients. There was a linear correlation (r = 0.69) between LV end-diastolic volume (EDV) by cineangiography and LV end-diastolic dimension (LVDd) by echocardiography. In patients with LV end-diastolic pressure (EDP) less than 12 mmHg, the LV was markedly dilated before surgery, and LVDd was not normalized until half a year after surgery in half the cases. In 20 patients with LVEDP greater than 12 mmHg, LVDd was normalized in 17 patients up to half a year after surgery. In 11 patients with LV end-systolic dimension (LVDs) greater than 5.2 cm, LVDs was not normalized until six years post surgery in three patients. LVDd was improved six years after surgery in patients with LVDs less than 5.2 cm. Echocardiographically-determined LVDs less than 5.2 cm is recommended for preservation of LV function following aortic valve replacement. Steinberg, Benjamin A; Harrison, J Kevin; Frazier-Mills, Camille; Hughes, G Chad; Piccini, Jonathan P Transcatheter aortic valve replacement (TAVR) is a rapidly-evolving technology for patients with severe, calcific aortic stenosis. Although these procedures lessen many of the risks and complications of open surgical aortic valve replacement, there remain challenges with TAVR including electrophysiologic complications. Among TAVR prostheses, rates of conduction abnormalities (CAs) vary from less than 10% to more than 50%, with up to one-third of patients requiring placement of a permanent pacemaker following TAVR. Several predictors of CAs have been identified related to device selection, baseline conduction defects, and anatomical considerations. Current data support the hypothesis that CAs result primarily from mechanical compression of the specialized conduction system by the device, although other factors may be involved. Such abnormalities can arise immediately during the procedure or as late as several days after implantation, and can be transient or permanent. Currently, there are no clinical tools to identify patients at highest risk for CAs post-TAVR, or to predict the course of CAs in patients who experience them. Early data suggest outcomes may be worse in high-risk patients, and further studies are needed to identify these patients so as to minimize electrophysiologic complications and determine appropriate monitoring in this expanding population. Copyright © 2012 Mosby, Inc. All rights reserved. Michler, Robert E. Transcatheter aortic valve implantation (TAVI) has emerged for treating aortic stenosis in patients who are poor candidates for surgical aortic valve replacement. Currently, the balloon-expandable Edwards Sapien valve—which is usually implanted via a transfemoral or transapical approach—and the self-expanding CoreValve ReValving system—which is designed for retrograde application—are the most widely implanted valves worldwide. Although a promising approach for high-risk patients, the indication may be expanded to intermediate- and eventually low-risk patients in the future; however, doing so will require a better understanding of potential complications, risk factors for these complications, and strategies to individualize each patient to a different access route and a specific valve. This paper reviews the most relevant complications that may occur in patients who undergo catheter-based aortic valve implantation. PMID:23844292 Glauber, Mattia; Moten, Simon C.; Quaini, Eugenio; Solinas, Marco; Folliguet, Thierry A.; Meuris, Bart; Miceli, Antonio; Oberwalder, Peter J.; Rambaldini, Manfredo; Teoh, Kevin H. T.; Bhatnagar, Gopal; Borger, Michael A.; Bouchard, Denis; Bouchot, Olivier; Clark, Stephen C.; Dapunt, Otto E.; Ferrarini, Matteo; Fischlein, Theodor J. M.; Laufer, Guenther; Mignosa, Carmelo; Millner, Russell; Noirhomme, Philippe; Pfeiffer, Steffen; Ruyra-Baliarda, Xavier; Shrestha, Malakh Lal; Suri, Rakesh M.; Troise, Giovanni; Gersak, Borut Objective To define the benefit of sutureless and rapid deployment valves in current minimally invasive approaches in isolated aortic valve replacement. Methods A panel of 28 international experts with expertise in both minimally invasive aortic valve replacement and rapid deployment valves was constituted. After thorough literature review, the experts rated evidence-based recommendations in a modified Delphi approach. Results No guideline could be retrieved. Thirty-three clinical trials and 9 systematic reviews could be identified for detailed text analysis to obtain a total of 24 recommendations. After rating by the experts 12, final recommendations were identified: preoperative computed tomographic scan as well as intraoperative transesophageal echocardiography are highly recommended. Suitable annular sizes are 19 to 27 mm. There is a contraindication for bicuspid valves only for type 0 and for annular abscess or destruction due to infective endocarditis. The use of sutureless and rapid deployment valves reduces extracorporeal circulation and aortic cross-clamp time and leads to less early complications as prolonged ventilation, blood transfusion, atrial fibrillation, pleural effusions, paravalvular leakages and aortic regurgitation, and renal replacement therapy, respectively. These clinical outcomes result in reduced intensive care unit and hospital stay and reduced costs. The use of sutureless and rapid deployment valves will lead to a higher adoption rate of minimally invasive approaches in aortic valve replacement. Respect should be taken to a necessary short learning curve for both sutureless and minimally invasive programs. Conclusions Sutureless and rapid deployment aortic valve replacement together with minimally invasive approaches offers an attractive option in aortic valve placement for patients requiring biological valve replacement. PMID:27540996 Bowler, Meghan A.; Merryman, W. David Calcific aortic valve disease (CAVD) affects 25% of people over 65, and the late-stage stenotic state can only be treated with total valve replacement, requiring 85,000 surgeries annually in the US alone . As CAVD is an age-related disease, many of the affected patients are unable to undergo the open-chest surgery that is its only current cure. This challenge motivates the elucidation of the mechanisms involved in calcification, with the eventual goal of alternative preventative and therapeutic strategies. There is no sufficient animal model of CAVD, so we turn to potential in vitro models. In general, in vitro models have the advantages of shortened experiment time and better control over multiple variables compared to in vivo models. As with all models, the hypothesis being tested dictates the most important characteristics of the in vivo physiology to recapitulate. Here, we collate the relevant pieces of designing and evaluating aortic valve calcification so that investigators can more effectively draw significant conclusions from their results. PMID:25249188 Garot, Jerome; Neylon, Antoinette; Sawaya, Fadi J.; Lefèvre, Thierry Progressive dyspnea and hypoxaemia in the subacute phase after transcatheter aortic valve implantation (TAVI) are uncommon and warrant immediate assessment of valve and prosthesis leaflet function to exclude thrombosis, as well as investigation for other causes related to the procedure, such as left ventricular dysfunction, pulmonary embolism, and respiratory sepsis. In this case, we report the observation of a patient presenting two weeks after TAVI with arterial hypoxaemia in an upright position, relieved by lying flat, and coupled with an intracardiac shunt detected on echocardiography in the absence of pulmonary hypertension, raising the suspicion of Platypnea-Orthodeoxia Syndrome (POS). Invasive intracardiac haemodynamic assessment showed a significant right-to-left shunt (Qp/Qs = 0.74), which confirmed the diagnosis, with subsequent closure of the intracardiac defect resulting in immediate relief of symptoms and hypoxaemia. To our knowledge, this is the first reported case of an interatrial defect and shunt causing Platypnea-Orthodeoxia Syndrome after transcatheter aortic valve implantation, resolved by percutaneous device closure. PMID:27610250 Giannini, Francesco; Ruparelia, Neil; Del Furia, Francesca; Romano, Vittorio; Ancona, Marco; Mangieri, Antonio; Regazzoli, Damiano; Latib, Azeem; Godino, Cosmo; Ancona, Francesco; Candilio, Luciano; Jabbour, Richard; Colombo, Antonio; Montorfano, Matteo Although the rate of procedural complications during transcatheter aortic valve implantation has decreased because of technological advancement and increased operator experience, device embolization remains a rare but potentially fatal complication, even with new generation devices. We report, to our knowledge, the first case of Portico valve (St Jude Medical, Minneapolis, MN) migration despite apparent optimal initial implantation depth, which was retrieved using a novel strategy after failure of a traditional retrieval technique. We also describe a mechanism of left coronary artery systolic perfusion with diastolic backflow, which led to myocardial ischemia. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. Etz, Christian D.; Misfeld, Martin; Borger, Michael A.; Luehr, Maximilian; Strotdrees, Elfriede; Mohr, Friedrich-Wilhelm Preventive surgical repair of the moderately dilated ascending aorta/aortic root in patients with bicuspid aortic valve (BAV) is controversial. Most international reference centers are currently proposing a proactive approach for BAV patients with a maximum ascending aortic/root diameter of 45 mm since the risk of dissection/rupture raises significantly with an aneurysm diameter >50 mm. Current guidelines of the European Society of Cardiology (ESC) and the joint guidelines of the American College of Cardiology (ACC)/American Heart Association (AHA) recommend elective repair in symptomatic patients with dysfunctional BAV (aortic diameter ≥45 mm). In asymptomatic patients with a well-functioning BAV, elective repair is recommended for diameters ≥50 mm, or if the aneurysm is rapidly progressing (rate of 5 mm/year), or in case of a strong family history of dissection/rupture/sudden death, or with planned pregnancy. As diameter is likely not the most reliable predictor of rupture and dissection and the majority of BAV patients may never experience an aortic catastrophe at small diameters, an overly aggressive approach almost certainly will put some patients with BAV unnecessarily at risk of operative and early mortality. This paper discusses the indications for preventive, elective repair of the aortic root, and ascending aorta in patients with a BAV and a moderately dilated—or ectatic—ascending aorta. PMID:23050195 Dall'Ara, Gianni; Saia, Francesco; Moretti, Carolina; Marrozzini, Cinzia; Taglieri, Nevio; Bordoni, Barbara; Chiarabelli, Matteo; Ciuca, Cristina; Rapezzi, Claudio; Marzocchi, Antonio To evaluate the incidence, treatment, and outcomes of acute aortic regurgitation (ARR) complicating BAV. In the transcatheter aortic valve implantation (TAVI) era, there is an increase of percutaneous balloon aortic valvuloplasty (BAV) procedures with different indications. From the prospective BAV registry of the University of Bologna, which has enrolled patients between the year 2000 and the present, we selected those who suffered intraprocedural AAR with overt hemodynamic instability. Worsening of baseline aortic insufficiency without hemodynamic collapse, treatment of degenerated biological valve prosthesis, and BAV performed within a planned TAVI procedure were excluded. The main endpoints were in-hospital and 30-day mortality. Out of 1517 BAVs, we identified 26 cases of AAR (1.7%). This complication occurred in 80.8% of cases after one or two balloon inflations. Mean transaortic gradient decreased from 50.6 ± 19.3 to 26.0 ± 14.4 mm Hg (p < 0.01). In 8(30.8%) patients, AAR spontaneously resolved within few minutes; in 18 cases, the operators had to perform a rescue maneuver to reposition a valve leaflet got stuck in the opening position (this maneuver was successful in 13/18 of the cases, 72.2%). Out of 5 persistent AAR, 3 were managed with emergency TAVI or surgery, while 2 were unresolved. In-hospital mortality was 15.4% (n = 4), whereas no more deaths occurred up to 30 days. AAR is a fearsome complication of BAV and portends a grim prognosis. In some cases, it can be resolved with appropriate technical maneuvers; in others, a rescue TAVI or surgical valve replacement may be necessary. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc. Guglielmetti, Laura; Nazif, Tamim; Sorabella, Robert; Akkoc, Deniz; Kantor, Alex; Gomez, Andres; Wang, Catherine; Takayama, Hiroo; Dizon, Jose; Borger, Michael; George, Isaac We aimed to assess the incidence and possible differences in postoperative conduction delay after aortic root replacement (ARR) in bicuspid aortic valve (BAV) patients compared with a tricuspid aortic valve (TAV). A total of 380 patients undergoing ARR at our institution between 2005 and 2013 were included in the analysis. Patients were stratified by aortic valve anatomy: BAV, n = 191 vs TAV, n = 189. Electrocardiographic and echocardiographic data were retrospectively analysed at different time points (pre-, postoperatively and at follow-up). Primary outcome of interest was permanent pacemaker (PPM) implantation within 30 days, the composite of new PPM or new left fascicular or bundle branch block (PPM or LBBB) was the secondary outcome of interest. Age range was 24-89.5 years and incidence of preoperative moderate to severe aortic stenosis was 9.7%. BAV patients had higher incidence of PPM implantation within 30 days (5.8 vs 1.6% in TAV, P = 0.053); moreover, the composite of PPM or LBBB was also more frequent in BAV (8.4 vs 2.1%, P = 0.010). BAV was independently associated with PPM insertion (OR 4.08, P = 0.047) and also an independent predictor of PPM or LBBB in multiple regression (OR 4.96, P = 0.006). Significantly higher incidence of PPM implantation or LBBB may exist after ARR in bicuspid patients and BAV was confirmed to be an independent predictor for postoperative conduction disturbances by multivariable regression. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. Syedain, Zeeshan; Reimer, Jay; Schmidt, Jillian; Lahti, Matthew; Berry, James; Bianco, Richard; Tranquillo, Robert T. Diseased aortic valves often require replacement, with over 30% of the current aortic valve surgeries performed in patients who will outlive a bioprosthetic valve. While many promising tissue-engineered valves have been created in the lab using the cell-seeded polymeric scaffold paradigm, none have been successfully tested long-term in the aortic position of pre-clinical model. The high pressure gradients and dynamic flow across the aortic valve leaflets require engineering a tissue that has the strength and compliance to withstand high mechanical demand without compromising normal hemodynamics. A long-term preclinical evaluation of an off-the-shelf tissue-engineered aortic valve in sheep model is presented here. The valves were made from a tube of decellularized cell-produced matrix mounted on a frame. The engineered tissue matrix is primarily composed of collagen, with strength and organization comparable to native valve leaflets. In vitro testing showed excellent hemodynamic performance with low regurgitation, low systolic pressure, and large orifice area. The implanted valves showed large-scale leaflet motion and maintained effective orifice area throughout the duration of the 6-month implant, with no calcification. After 24 weeks implantation (over 17 million cycles), the valves showed no change in tensile mechanical properties or collagen content. In addition, histology and DNA quantitation showed repopulation of the engineered matrix with interstitial-like cells and endothelialization. New extracellular matrix deposition, including elastin, further demonstrates positive tissue remodeling in addition to recellularization and valve function. Long-term implantation in the sheep model resulted in functionality, matrix remodeling, and recellularization, unprecedented results for a tissue-engineered aortic valve. PMID:26409002 Kent, Kathleen C.; Crenshaw, Melissa L.; Goh, Denise L. M.; Dietz, Harry C. Objectives Bicuspid aortic valve is the most common congenital cardiac abnormality, occurring in 1% to 2% of the population, and often associates with ascending aortic aneurysm. Based on familial studies, bicuspid aortic valve with aneurysm segregates in an autosomal dominant manner with incomplete penetrance. NOTCH1 mutations have been reported in 6 families with prominent valve calcification and dysfunction and low penetrance of aneurysm. We sought to determine the contribution of NOTCH1 mutations to the more common phenotype of highly penetrant aneurysms with low penetrance of bicuspid aortic valve and with rare valve calcification or dysfunction. Methods All exons and splice junctions of NOTCH1 were sequenced in probands from 13 affected families presenting with bicuspid aortic valve with ascending aortic aneurysm in the absence of valve calcification. In addition, mutation analysis was performed on a single individual with aneurysm and calcified tricuspid aortic valve. Sequences were aligned and compared with the reference genomic sequence. Results Corroborating previous studies, analysis of the single sporadic patient with calcified aortic valve in the presence of ascending aortic aneurysm revealed a novel heterozygous missense mutation in NOTCH1 resulting in a nonsynonymous amino acid substitution (p.T1090S, c.C3269G) of an evolutionarily conserved residue. This change was not observed in controls. In contrast, we did not identify any pathologic NOTCH1 mutations in the 13 families segregating noncalcified bicuspid aortic valve with highly penetrant aortic aneurysm. Conclusions These data suggest that there are phenotypic differences that distinguish families with and without NOTCH1 mutations, indicating a genotype–phenotype correlation with potential implications for patient diagnosis, counseling, and management. PMID:23102684 Commeau, P; Grollier, G; Lamy, E; Foucault, J P; Durand, C; Maffei, G; Maiza, D; Khayat, A; Potier, J C Two groups of elderly patients with calcified aortic stenosis were treated by balloon dilatation. In group 1, the valve was dilated just before surgical replacement of the valve. The valvar and annular changes occurring during dilatation were examined visually. In 20 of the 26 patients in this group there was no change. In the six remaining patients mobilisation of friable calcific deposits (1 case), slight tearing of the commissure (4 cases), or tearing of the aortic ring (1 case) were seen. Dilatation did not appear to alter valvar rigidity. In 14 patients (group 2) the haemodynamic gradient across the aortic valve was measured before and immediately after dilatation and one week after the procedure. Dilatation produced an immediate significant decrease of the aortic mean gradient and a significant increase of the aortic valve area. Eight days later the mean gradient had increased and the aortic valve area had decreased. Nevertheless there was a significant difference between the initial gradient and the gradient eight days after dilatation. The initial aortic valve area was also significantly larger than the area eight days after dilatation. The aortic valve gradient rose significantly in the eight days after dilatation and at follow up the gradients were those of severe aortic stenosis. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 Fig 7 PMID:3342163 Blanke, Philipp; Soon, Jeanette; Dvir, Danny; Park, Jong K; Naoum, Christopher; Kueh, Shaw-Hua; Wood, David A; Norgaard, Bjarne L; Selvakumar, Kapilan; Ye, Jian; Cheung, Anson; Webb, John G; Leipsic, Jonathon Valve-in-valve implantation of a transcatheter heart valve into a failed bioprosthetic heart valve has emerged as a treatment alternative to repeat conventional surgery. This requires careful pre-procedural assessment using non-invasive imaging to identify patients at risk for procedure related adverse events, such as ostial coronary occlusion. Herein we report how to comprehensively assess aortic root anatomy using computed tomography prior to transcatheter valve implantation for failed bioprosthetic aortic valves. Meredith Am, Ian T; Walters, Darren L; Dumonteil, Nicolas; Worthley, Stephen G; Tchétché, Didier; Manoharan, Ganesh; Blackman, Daniel J; Rioufol, Gilles; Hildick-Smith, David; Whitbourn, Robert J; Lefèvre, Thierry; Lange, Rüdiger; Müller, Ralf; Redwood, Simon; Allocco, Dominic J; Dawkins, Keith D Transcatheter aortic valve replacement provides results comparable to those of surgery in patients at high surgical risk, but complications can impact long-term outcomes. The Lotus valve, designed to improve upon earlier devices, is fully repositionable and retrievable, with a unique seal to minimize paravalvular regurgitation (PVR). The prospective, single-arm, multicenter REPRISE II study (REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus Valve System: Evaluation of Safety and Performance) evaluated the transcatheter valve system for treatment of severe symptomatic calcific aortic valve stenosis. Patients (n = 120; aortic annulus 19 to 27 mm) considered by a multidisciplinary heart team to be at high surgical risk received the valve transfemorally. The primary device performance endpoint, 30-day mean pressure gradient, was assessed by an independent echocardiographic core laboratory and compared with a pre-specified performance goal. The primary safety endpoint was 30-day mortality. Secondary endpoints included safety/effectiveness metrics per Valve Academic Research Consortium criteria. Mean age was 84.4 years, 57% of the patients were female, and 76% were New York Heart Association functional class III/IV. Mean aortic valve area was 0.7 ± 0.2 cm(2). The valve was successfully implanted in all patients, with no cases of valve embolization, ectopic valve deployment, or additional valve implantation. All repositioning (n = 26) and retrieval (n = 6) attempts were successful; 34 patients (28.6%) received a permanent pacemaker. The primary device performance endpoint was met, because the mean gradient improved from 46.4 ± 15.0 mm Hg to 11.5 ± 5.2 mm Hg. At 30 days, the mortality rate was 4.2%, and the rate of disabling stroke was 1.7%; 1 (1.0%) patient had moderate PVR, whereas none had severe PVR. REPRISE II demonstrates the safety and effectiveness of the Lotus valve in patients with severe aortic stenosis who are at Takakura, H; Sasaki, T; Hashimoto, K; Hachiya, T; Onoguchi, K; Oshiumi, M; Takeuchi, S Three female patients with aortic stenosis associated with a severely small annulus underwent aortic valve replacement. In intraoperative measurements, a 19-mm obtulator could not pass through the aortic annulus in each case. We therefore concluded that it would be difficult to implant an appropriate-sized prosthesis in a routine fashion, so we performed an annular enlargement in a modified Nicks procedure. By using a wide teardrop-shaped patch for enlargement and slightly tilting insertion of a prosthesis, a 21 mm bileaflet mechanical prosthesis could be inserted into the enlarged annulus. Despite being a simpler method than other enlarging procedures, a two- or three-sizes larger prosthesis than the native annulus can be inserted with relative ease. Thus, the use of a 19 mm mechanical prosthesis may be avoidable in most adult cases. Bobylev, Dmitry; Breymann, Thomas; Ono, Masamichi This article puts forward a modified technique of Konno aortoventriculoplasty for repeat procedures. After incision of the ventricular septum, this approach involves aortic valve replacement using a mechanical valved conduit, reimplantation of the coronary arteries, and graft replacement of the ascending aorta. This modification allows the removal of the diseased ascending aortic wall caused by a previous patch enlargement or poststenotic dilation. McKellar, Stephen H; Deo, Salil; Daly, Richard C; Durham, Lucian A; Joyce, Lyle D; Stulak, John M; Park, Soon J A competent aortic valve is essential to providing effective left ventricular assist device support. We have adopted a practice of central aortic valve closure by placing a simple coaptation stitch at left ventricular assist device implantation in patients with significant aortic insufficiency. We conducted a follow-up study to evaluate the efficacy and durability of this procedure. The study included patients who had undergone continuous flow left ventricular assist device implantation. The patients were divided into 2 groups, those who did not require any aortic procedure because the valve was competent and those who underwent central aortic valve closure for mild or greater aortic regurgitation. The clinical endpoints were mortality, progression or recurrence of aortic insufficiency, and reoperation for aortic valve pathologic features. Aortic insufficiency was measured qualitatively from mild to severe on a scale of 0 to 5. A total of 123 patients received continuous flow left ventricular assist devices from February 2007 to August 2011. Of those, 18 (15%) underwent central aortic valve closure at left ventricular assist device implantation because of significant aortic insufficiency (1.8 ± 1.4) and 105 who did not (competent aortic valve, 0.15 ± 0.43; P < .01). At follow-up (median, 312 days; range, 0-1429 days), the mean aortic insufficiency score remained low for the patients with central aortic valve closure (0.27 ± 0.46) in contrast to those without central aortic valve closure who experienced aortic insufficiency progression (0.78 ± 0.89; P = .02). In addition, the proportion of patients with more than mild aortic insufficiency was significantly less in the central aortic valve closure group (0% vs 18%; P = .05). The patients in the central aortic valve closure group were significantly older and had a greater incidence of renal failure at baseline. The 30-day mortality was greater in the central aortic valve closure group, but the late survival Norimatsu, Kenji; Miura, Shin-Ichiro; Suematsu, Yasunori; Shiga, Yuhei; Miyase, Yuiko; Nakamura, Ayumi; Zhang, Bo; Saku, Keijiro Aortic valve calcification (AVC) reflects the state of aortic valve sclerosis (AVS), which is a precursor to aortic valve stenosis (AS). Therefore, we investigated the presence of AVC in patients who underwent coronary computed tomography angiography (CTA), which is an effective tool for evaluating early-stage AVC, and examined the association between plasma levels of pentraxin 3 (PTX3) and AVC. The subjects consisted of 162 consecutive patients who underwent CTA and in whom we could measure plasma levels of PTX3. We divided the patients into an AVC group (n=42) and a non-AVC group (n=120), as assessed by CT. Furthermore, we divided the patients without AS, assessed by echocardiography, into non-AS AVC (n=23) and non-AS non-AVC groups (n=60). We analyzed the predictors of the presence of AVC in all patients by a logistic regression analysis. AVC was independently associated with PTX3, in addition to age, chronic kidney disease, and coronary artery calcification. We also examined the predictors of the presence of AVC in patients without AS. PTX3, in addition to age, was an independent predictor of the presence of AVC in patients without AS. Finally, we found that adding PTX3 to the model containing age improves the specificity and, therefore, positive predictive value for AVC. PTX3, in addition to age, was shown to be an independent predictor of AVC in patients without AS. The combination of age and PTX3 may be a better approach to the evaluation of AVC than either of these alone. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved. Greason, Kevin L; Mathew, Verghese; Wiesner, Russel H; Suri, Rakesh M; Rihal, Charanjit S Patients with cirrhosis who undergo cardiac operation with extracorporeal circulation are at high risk for operative morbidity and mortality. Transcatheter aortic valve replacement (TAVR) can obviate the need for cardiopulmonary bypass and may reduce operative morbidity in comparison to standard aortic valve replacement (SAVR) in select patients. Review of 18 patients with aortic valve stenosis and cirrhosis treated with TAVR (n=6) or SAVR (n=12). Patient age was 71 years (58 to 83) and STS Predicted Risk of Mortality was 3.2% (0.7 to 12.3). There were 15 males (83%). Child-Turcotte-Pugh stage was A in 10 patients (56%), B in four (22%), and C in two (11%); the median MELD score was nine (7 to 14). TAVR was successful in all patients without the need for mechanical or cardiopulmonary bypass support. Blood transfusion occurred in four patients (67%) in the TAVR group and in the entire SAVR group. No deaths occurred in the TAVR group, and two (17%) occurred in the SAVR group. Operative complications occurred in two patients (33%) in TAVR group and in eight (67%) in the SAVR group. Hospital stay was five days (3 to 10) in the TAVR group and six (3 to 38) in the SAVR group. All TAVR patients were alive at last follow-up of 219 days (29 to 723), while only five were alive in the SAVR group at 228 days (36 to 719). Our initial experience with TAVR in patients with cirrhosis is encouraging. The technique may be a viable alternative to SAVR in this high-risk subset of patients. © 2013 Wiley Periodicals, Inc. Kaminishi, Yuichiro; Misawa, Yoshio; Kobayashi, Junjiro; Konishi, Hiroaki; Miyata, Hiroaki; Motomura, Noboru; Takamoto, Shin-ichi Patient-prosthesis mismatch (PPM) may affect clinical outcomes in patients with aortic valve replacement (AVR). We retrospectively examined the PPM in patients with isolated AVR in the Japan Adult Cardiovascular Surgery Database (JACVSD). We examined all patients with isolated AVR between January 1, 2008 and December 31, 2009. The JACVSD data collection form has a total of 255 variables. We defined PPM as an effective orifice area index of ≤ 0.85 m(2)/cm(2). PPM was observed in 306 of 3,609 cases analyzed, PPM rate was 8.5 %. Body surface area was larger and body mass index was higher in the PPM group than the non-PPM group (P < 0.001). Patients with PPM were older (P = 0.001) and had a higher prevalence of diabetes (P = 0.004), dyslipidemia (P < 0.001), hypertension (P < 0.001), cerebrovascular disease (P = 0.031), old myocardial infarction (P = 0.006), previous percutaneous coronary artery intervention (P = 0.001), coronary artery disease (P = 0.018), and aortic valve stenosis (P < 0.001). Perioperative blood transfusion (P < 0.001) and dialysis (P = 0.005) were more frequent in the PPM group. Postoperative ventilation (P = 0.004) and intensive care unit stay (P = 0.004) were significantly longer in the PPM group. Age, aortic valve stenosis, dyslipidemia, hypertension, old myocardial infarction, previous percutaneous coronary artery intervention, diabetes mellitus, cerebrovascular disease, and high body mass index were the risk factors for PPM. PPM was not an independent risk factor for short-term mortality. Meyer, Steven R; Chiu, Brian; Churchill, Thomas A; Zhu, Linfu; Lakey, Jonathan R T; Ross, David B Rodent models have been essential to understanding the immune-mediated failure of aortic valve allografts (AVAs). Decellularization has been proposed to reduce the immunogenicity of AVAs. The objective of this study was to determine the most effective method to decellularize AVAs for use in a rat model. Three different decellularization techniques were compared in Lewis aortic valves. Detergent decellularization involved a series of hypotonic and hypertonic Tris buffers at 4 degrees C for 48 h/buffer containing 0.5% Triton X-100 followed by a 72 h washout in phosphate-buffered saline. Osmotic decellularization was performed in similar manner to the detergent-based technique except without the addition of Triton X-100. Enzymatic decellularization consisted of trypsin/EDTA at 37 degrees C for 48 h. Assessment was performed with light microscopy (H&E, Movat's pentachrome), immunohistochemistry for residual cellular elements, and hydroxyproline assays. Detergent-based methodology effected near-complete decellularization of both the leaflets and aortic wall in addition to preservation of the extracellular matrix (ECM). Osmotic lysis was associated with preservation of ECM and moderate decellularization. Enzymatic decellularization resulted in complete decellularization but extensive degeneration and fragmentation of the ECM. When implanted into the infrarenal aorta of allogeneic rats for 1 week, valves decellularized with detergent-based and osmotic methodology failed to stimulate an allogeneic immune response as evidenced by an absence of T cell infiltrates. Osmotic lysis protocols with low dose detergent appear to be most effective at both removing antigenic cellular elements and preserving ECM. Miura, Y; Miyairi, T; Kitamura, T; Kigawa, I; Fukuda, S We studied cardiac function, clinical outcome and quality of life (QOL) long after aortic valve replacement for pure aortic stenosis. Forty-four patients in small group [St. Jude Medical (SJM) 17 HP, 19 A], and 69 patients in non-small group (19 HP, 21 A, 23 A) operated on from 1984 to 2004 were enrolled in this study. We assessed the clinical data, aortic pressure gradient, left ventricular mass index (LVMI), and ejection fraction (EF) by preoperative and postoperative echocardiography. Moreover to evaluate QOL after the operation, we performed SF-36 used for the evaluation of health and QOL worldwide. Mean follow-up is 7.1 +/- 4.8 years in small group, and 6.8 +/- 4.6 years in non-small group. There were 2 hospital deaths in small group, and 1 in non-small group. The actual survival rate at 10-year were 89.2% in small group, and 85.6% in non-small group. There was no significant difference in hospital mortality, LVMI, long-term survival rate, and the scores of SF-36 between the 2 groups. The use of small sized prosthetic valves in patients with small aortic annulus might be justified when there is no patient-prosthesis mismatch. Wendell, David C; Samyn, Margaret M; Cava, Joseph R; Ellwein, Laura M; Krolikowski, Mary M; Gandy, Kimberly L; Pelech, Andrew N; Shadden, Shawn C; LaDisa, John F Computational fluid dynamics (CFD) simulations quantifying thoracic aortic flow patterns have not included disturbances from the aortic valve (AoV). 80% of patients with aortic coarctation (CoA) have a bicuspid aortic valve (BAV) which may cause adverse flow patterns contributing to morbidity. Our objectives were to develop a method to account for the AoV in CFD simulations, and quantify its impact on local hemodynamics. The method developed facilitates segmentation of the AoV, spatiotemporal interpolation of segments, and anatomic positioning of segments at the CFD model inlet. The AoV was included in CFD model examples of a normal (tricuspid AoV) and a post-surgical CoA patient (BAV). Velocity, turbulent kinetic energy (TKE), time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) results were compared to equivalent simulations using a plug inlet profile. The plug inlet greatly underestimated TKE for both examples. TAWSS differences extended throughout the thoracic aorta for the CoA BAV, but were limited to the arch for the normal example. OSI differences existed mainly in the ascending aorta for both cases. The impact of AoV can now be included with CFD simulations to identify regions of deleterious hemodynamics thereby advancing simulations of the thoracic aorta one step closer to reality. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved. Wendell, David C.; Samyn, Margaret M.; Cava, Joseph R.; Ellwein, Laura M.; Krolikowski, Mary M.; Gandy, Kimberly L.; Pelech, Andrew N.; Shadden, Shawn C.; LaDisa, John F. Computational fluid dynamics (CFD) simulations quantifying thoracic aortic flow patterns have not included disturbances from the aortic valve (AoV). 80% of patients with aortic coarctation (CoA) have a bicuspid aortic valve (BAV) which may cause adverse flow patterns contributing to morbidity. Our objectives were to develop a method to account for the AoV in CFD simulations, and quantify its impact on local hemodynamics. The method developed facilitates segmentation of the AoV, spatiotemporal interpolation of segments, and anatomic positioning of segments at the CFD model inlet. The AoV was included in CFD model examples of a normal (tricuspid AoV) and a post-surgical CoA patient (BAV). Velocity, turbulent kinetic energy (TKE), time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) results were compared to equivalent simulations using a plug inlet profile. The plug inlet greatly underestimated TKE for both examples. TAWSS differences extended throughout the thoracic aorta for the CoA BAV, but were limited to the arch for the normal example. OSI differences existed mainly in the ascending aorta for both cases. The impact of AoV can now be included with CFD simulations to identify regions of deleterious hemodynamics thereby advancing simulations of the thoracic aorta one step closer to reality. PMID:22917990 Moss, Alastair J; Dweck, Marc R; Dreisbach, John G; Williams, Michelle C; Mak, Sze Mun; Cartlidge, Timothy; Nicol, Edward D; Morgan-Hughes, Gareth J Aortic valve replacement is the second most common cardiothoracic procedure in the UK. With an ageing population, there are an increasing number of patients with prosthetic valves that require follow-up. Imaging of prosthetic valves is challenging with conventional echocardiographic techniques making early detection of valve dysfunction or complications difficult. CT has recently emerged as a complementary approach offering excellent spatial resolution and the ability to identify a range of aortic valve replacement complications including structural valve dysfunction, thrombus development, pannus formation and prosthetic valve infective endocarditis. This review discusses each and how CT might be incorporated into a multimodal cardiovascular imaging pathway for the assessment of aortic valve replacements and in guiding clinical management. PMID:27843568 Barbanti, Marco; Petronio, Anna Sonia; Ettori, Federica; Latib, Azeem; Bedogni, Francesco; De Marco, Federico; Poli, Arnaldo; Boschetti, Carla; De Carlo, Marco; Fiorina, Claudia; Colombo, Antonio; Brambilla, Nedy; Bruschi, Giuseppe; Martina, Paola; Pandolfi, Claudia; Giannini, Cristina; Curello, Salvatore; Sgroi, Carmelo; Gulino, Simona; Patanè, Martina; Ohno, Yohei; Tamburino, Claudia; Attizzani, Guilherme F; Immè, Sebastiano; Gentili, Alessandra; Tamburino, Corrado The purpose of this analysis was to assess 5-year outcomes of transcatheter aortic valve implantation (TAVI) using the current technology of the self-expanding CoreValve prosthesis (Medtronic Inc., Minneapolis, Minnesota). There is a paucity of evidence on long-term durability of currently available transcatheter heart valves. Starting in June 2007, all consecutive patients with severe aortic stenosis undergoing TAVI with the third-generation 18-F CoreValve device in 8 Italian centers were prospectively included in the ClinicalService Project. For the purposes of this study, we included only consecutive patients with 5-year follow-up data available (n = 353) treated from June 2007 to August 2009. All outcomes were reported according to VARC (Valve Academic Research Consortium)-1 criteria. All-cause mortality rates at 1, 2, 3, 4, and 5 years were 21%, 29%, 38%, 48%, and 55.0%, respectively. Cardiovascular mortality rates at 1, 2, 3, 4, and 5 years were 10%, 14%, 19%, 23%, and 28.0%, respectively. The overall neurological event rate at 5 years was 7.5%, of which more than two-thirds occurred early after the procedure. During follow-up, there were 241 rehospitalizations for cardiovascular reasons in 164 (46%) patients. Among all rehospitalizations, acute heart failure was the most frequently reported (42.7%), followed by requirement of permanent pacemaker implantation (17.4%). On echocardiography, mean transaortic gradients decreased from 55.6 ± 16.8 mm Hg (pre-TAVI) to 12.8 ± 10.9 mm Hg (5-year post-TAVI) (p < 0.001). Late prosthesis failure occurred in 5 cases (1.4%); among these, redo TAVI was successfully carried out in 2 patients (0.6%) presenting with symptomatic prosthesis restenosis. The remaining 3 cases of prosthesis failure did not undergo further invasive interventions. Ten patients (2.8%) showed late mild stenosis with a mean transaortic gradient ranging from 20 to 40 mm Hg. No other cases of structural or nonstructural valvular deterioration were Lee, Candice Y; Wong, Joshua K; Ross, Ronald E; Liu, David C; Khabbaz, Kamal R; Martellaro, Angelo J; Gorea, Heather R; Sauer, Jude S; Knight, Peter A Prostheses attachment is critical in aortic valve replacement surgery, yet reliable prosthetic security remains a challenge. Accurate techniques to analyze prosthetic fixation pressures may enable the use of fewer sutures while reducing the risk of paravalvular leaks (PVL). Customized digital thin film pressure transducers were sutured between aortic annulus models and 21-mm bioprosthetic valves with 15 × 4-mm, 12 × 4-mm, or 9 × 6-mm-wide pledgeted mattress sutures. Simulating open and minimally invasive access, 4 surgeons, blinded to data acquisition, each secured 12 valves using manual knot-tying (hand-tied [HT] or knot-pusher [KP]) or automated titanium fasteners (TFs). Real-time pressure measurements and times were recorded. Two-dimensional (2D) and 3D pressure maps were generated for all valves. Pressures less than 80 mm Hg were considered at risk for PVL. Pressures under each knot (intrasuture) fell less than 80 mm Hg for 12 of 144 manual knots (5/144 HT, 7/144 KP) versus 0 of 288 TF (P < 0.001). Pressures outside adjacent sutures (extrasuture) were less than 80 mm Hg in 10 of 60 HT, zero of 60 KP, and zero of 120 TF sites for 15 × 4-mm valves; 17 of 48 HT, 25 of 48 KP, and 12 of 96 TF for 12 × 4-mm valves; and 15 of 36 HT, 17 of 36 KP, and 9 and 72 TF for 9 × 6-mm valves; P < 0.001 all manual versus TF. Annular areas with pressures less than 80 mm Hg ranged from 0% of the sewing-ring area (all open TF) to 31% (12 × 4 mm, KP). The average time per manual knot, 46 seconds (HT, 31 seconds; KP, 61 seconds), was greater than TF, 14 seconds (P < 0.005). Reduced operative times and PVL risk would fortify the advantages of surgical aortic valve replacement. This research encourages continued exploration of technical factors in optimizing prosthetic valve security. Grewal, Nimrat; Franken, Romy; Mulder, Barbara J M; Goumans, Marie-José; Lindeman, Johannes H N; Jongbloed, Monique R M; DeRuiter, Marco C; Klautz, Robert J M; Bogers, Ad J J C; Poelmann, Robert E; Groot, Adriana C Gittenberger-de Patients with bicuspid aortic valve (BAV) and patients with Marfan syndrome (MFS) are more prone to develop aortic dilation and dissection compared to persons with a tricuspid aortic valve (TAV). To elucidate potential common and distinct pathways of clinical relevance, we compared the histopathological substrates of aortopathy. Ascending aortic wall biopsies were divided in five groups: BAV (n = 36) and TAV (n = 23) without and with dilation and non-dilated MFS (n = 8). General histologic features, apoptosis, the expression of markers for vascular smooth muscle cell (VSMC) maturation, markers predictive for ascending aortic dilation in BAV, and expression of fibrillin-1 were investigated. Both MFS and BAV showed an altered distribution and decreased fibrillin-1 expression in the aorta and a significantly lower level of differentiated VSMC markers. Interestingly, markers predictive for aortic dilation in BAV were not expressed in the MFS aorta. The aorta in MFS was similar to the aorta in dilated TAV with regard to the presence of medial degeneration and apoptosis, while other markers for degeneration and aging like inflammation and progerin expression were low in MFS, comparable to BAV. Both MFS and BAV aortas have immature VSMCs, while MFS and TAV patients have a similar increased rate of medial degeneration. However, the mechanism leading to apoptosis is expected to be different, being fibrillin-1 mutation induced increased angiotensin-receptor-pathway signaling in MFS and cardiovascular aging and increased progerin in TAV. Our findings could explain why angiotensin inhibition is successful in MFS and less effective in TAV and BAV patients. Doi, Atsuo; Marasco, Silvana F; McGiffin, David C Commissural fusion of the native aortic valve in a patient with a continuous flow left ventricular assist device (LVAD) is a known phenomenon. This may result in aortic insufficiency (AI) leading to symptomatic heart failure. In patients with AI at the time of LVAD implantation, repairing, or replacing the aortic valve is advisable. We describe a patient who had a severe dilated cardiomyopathy and moderate AI who underwent implantation of an LVAD and aortic valve replacement with a bioprosthesis that subsequently developed commissural fusion which was found at the time of heart transplantation. This case highlights the conundrum of the management of AI in patients requiring LVAD support. Petroulaki, Aristea; Lazopoulos, George; Chaniotaki, Fotini; Kampitakis, Emmanuel; Pavlopoulos, Dionysis; Chalkiadakis, George Severe factor XI deficiency (hemophilia C) is a rare coagulation disorder. A 73-year-old woman, a homozygote for factor XI deficiency, required aortic valve replacement. An initial dose of 15 U kg(-1) of factor XI concentrate was administered preoperatively and on postoperative day 3. During surgery, concentrated red cells, fresh frozen plasma, platelets, tranexamic acid, and fibrinogen were transfused. Intraoperative bleeding and total chest drainage were minimal. Postoperatively, there was no need for further transfusions and no bleeding or thrombotic complications occurred. The patient was well 16 months after surgery. Lewis, Harriet; Benedetto, Umberto; Caputo, Massimo; Angelini, Gianni; Vohra, Hunaid A. Minimally invasive aortic valve replacement (AVR) aims to preserve the sternal integrity and improve postoperative outcomes. In low risk patients, this technique can be achieved with comparable mortality to the conventional approach and there is evidence of possible reduction in intensive care and hospital length of stay, transfusion requirement, renal dysfunction, improved respiratory function and increased patient satisfaction. In this review, we aim to asses if these benefits can be transferred to the high risk patient groups. We therefore, discuss the available evidence for the following high risk groups: elderly patients, re-operative surgery, poor lung function, pulmonary hypertension, obesity, concomitant procedures and high risk score cohorts. PMID:28740685 Sabzi, Feridoun; Niazi, Mojtaba; Ahmadi, Alireza Abstract: This case study concerns a patient with disruption of both tricuspid and aortic valves: a previously healthy, adult man, who sustained a 5-meter fall from a building under construction. The mechanism of the injury was acceleration and deceleration, acting in two different phases of the cardiac cycle, i.e. systole and diastole. Simultaneous occurrence of these injuries is exceedingly rare and in a careful literature review, we did not find any such combination of injury. The possible mechanisms of this injury, as well as surgical techniques are discussed. PMID:23511124 Patnaik, Soumya; Davila, Carlos Daniel; Chennupati, Anupama; Rubin, Alexander Lactobacilli are Gram-positive anaerobic rods or coccobacilli, commonly found as commensals in human mucosa. Rarely, they can cause serious infections such as infective endocarditis (IE), and the most frequently implicated species causing serious infections are L. casei and L. rhamnosus. IE caused by Lactobacillus jensenii is very rare, with only six reported cases so far, to the best of our knowledge. We present a case of native aortic valve endocarditis caused by L. jensenii, complicated by root abscess and complete heart block, and requiring emergent surgical intervention. PMID:25750218 Jenny, Benjamin E; Almanaseer, Yassar Infective endocarditis complicated by abscess formation and coronary artery compression is a rare clinical event with a high mortality rate, and diagnosis requires a heightened degree of suspicion. We present the clinical, angiographic, and echocardiographic features of a 73-year-old woman who presented with dyspnea and was found to have right coronary artery compression that was secondary to abscess formation resulting from diffuse infectious endocarditis. We discuss the patient's case and briefly review the relevant medical literature. To our knowledge, this is the first reported case of abscess formation involving a native aortic valve and the right coronary artery. Several disease pathologies such as congenital heart disease and rheumatic fever can affect the aortic valve (AV) in children frequently necessitating intervention. While percutaneous or surgical AV repair is recommended as initial management strategy in children with AV disease, AV replacement (AVR) might become necessary in children with significant valve destruction and after repair or intervention failure. AVR in children is associated with distinct clinical and technical problems owing to several anatomic, social and prosthesis-related issues. In the current review, we list different AV substitutes, discuss their advantages and shortcomings, outline AVR results in children, and explore the divergence of outcomes in various age, anatomy and pathology subgroups; all in the aim to identify optimal AVR choice for each patient taking into consideration his unique anatomic and demographic characteristics. PMID:24578598 Smith, J. Gustav; Luk, Kevin; Schulz, Christina-Alexandra; Engert, James C.; Do, Ron; Hindy, George; Rukh, Gull; Dufresne, Line; Almgren, Peter; Owens, David S.; Harris, Tamara B.; Peloso, Gina M.; Kerr, Kathleen F.; Wong, Quenna; Smith, Albert V.; Budoff, Matthew J.; Rotter, Jerome I.; Cupples, L. Adrienne; Rich, Stephen; Kathiresan, Sekar; Orho-Melander, Marju; Gudnason, Vilmundur; O’Donnell, Christopher J.; Post, Wendy S.; Thanassoulis, George IMPORTANCE Plasma low-density lipoprotein cholesterol (LDL-C) has been associated with aortic stenosis in observational studies; however, randomized trials with cholesterol-lowering therapies in individuals with established valve disease have failed to demonstrate reduced disease progression. OBJECTIVE To evaluate whether genetic data are consistent with an association between LDL-C, high-density lipoprotein cholesterol (HDL-C), or triglycerides (TG) and aortic valve disease. DESIGN, SETTING, AND PARTICIPANTS Using a Mendelian randomization study design, we evaluated whether weighted genetic risk scores (GRSs), a measure of the genetic predisposition to elevations in plasma lipids, constructed using single-nucleotide polymorphisms identified in genome-wide association studies for plasma lipids, were associated with aortic valve disease. We included community-based cohorts participating in the CHARGE consortium (n = 6942), including the Framingham Heart Study (cohort inception to last follow-up: 1971-2013; n = 1295), Multi-Ethnic Study of Atherosclerosis (2000-2012; n = 2527), Age Gene/Environment Study-Reykjavik (2000-2012; n = 3120), and the Malmö Diet and Cancer Study (MDCS, 1991-2010; n = 28 461). MAIN OUTCOMES AND MEASURES Aortic valve calcium quantified by computed tomography in CHARGE and incident aortic stenosis in the MDCS. RESULTS The prevalence of aortic valve calcium across the 3 CHARGE cohorts was 32% (n = 2245). In the MDCS, over a median follow-up time of 16.1 years, aortic stenosis developed in 17 per 1000 participants (n = 473) and aortic valve replacement for aortic stenosis occurred in 7 per 1000 (n = 205). Plasma LDL-C, but not HDL-C or TG, was significantly associated with incident aortic stenosis (hazard ratio [HR] per mmol/L, 1.28; 95% CI, 1.04-1.57; P = .02; aortic stenosis incidence: 1.3% and 2.4% in lowest and highest LDL-C quartiles, respectively). The LDL-C GRS, but not HDL-C or TG GRS, was significantly associated with presence of Fujimoto, K; Okamoto, H; Tamenishi, A; Niimi, T A 27-year-old man was injured during a motocross game. He was suffered from dyspnea, orthopnea, and hemoptysis. The to-and-fro murmur was noticed 3 days after the accident and then the patient was admitted to our hospital. Echocardiography revealed severe aortic regurgitation. Computerized tomography also showed severe pulmonary contusions. Seventeen days after the accident the aortic valve replacement was performed. The aortic valve was anterior-posterior type bicuspid valve (fusion of right coronary cusp and light coronary cusp) and the tear was detected in the anterior cusp. The postoperative course was uneventful. Rupture of the aortic valve due to a blunt chest trauma is rare and reported in 20 cases previously in Japan. This case is the second report of traumatic rupture of the bicuspid aortic valve. Bouchareb, Rihab; Côté, Nancy; Marie-Chloé-Boulanger; Le Quang, Khai; El Husseini, Diala; Asselin, Jérémie; Hadji, Fayez; Lachance, Dominic; Shayhidin, Elnur Elyar; Mahmut, Ablajan; Pibarot, Philippe; Bossé, Yohan; Messaddeq, Younes; Boudreau, Denis; Marette, André; Mathieu, Patrick Calcific aortic valve stenosis (CAVS) is the most common heart valve disease. In the present work we sought to determine the reversibility of mineralization in the aortic valve. By using in vitro analyses we found that valve interstitial cells (VICs) have the ability to resorb minerals. We documented that agonist of P2Y2 receptor (P2Y2R) promoted the expression of carbonic anhydrase XII (CAXII) at the cell membrane of VICs, whereby minerals are resorbed. P2Y2R-mediated mineral resorption was corroborated by using mouse VICs isolated from wild type and P2Y2R(-/-) mice. Measurements of extracellular pH (pHe) by using core-shell nanosensors revealed that P2Y2R-mediated CAXII export to the cell membrane led to an acidification of extracellular space, whereby minerals are resorbed. In vivo, we next treated LDLR(-/-)/ApoB(100/100)/IGF2 mice, which had developed CAVS under a high-fat/high-sucrose diet for 8 months, with 2-thioUTP (a P2Y2R agonist) or saline for the next 2 months. The administration of 2-thioUTP (2mg/kg/day i.p.) reduced the mineral volume in the aortic valve measured with serial microCT analyses, which improved hemodynamics and reduced left ventricular hypertrophy (LVH). Examination of leaflets at necropsy confirmed a lower level of mineralization and fibrosis along with higher levels of CAXII in mice under 2-thioUTP. In another series of experiment, the administration of acetazolamide (a CA inhibitor) prevented the acidification of leaflets and the regression of CAVS induced by 2-thioUTP in LDLR(-/-)/ApoB(100/100)/IGF2 mice. P2Y2R-mediated expression of CAXII by VICs acidifies the extracellular space and promotes the regression of CAVS. Copyright © 2015 Elsevier Ltd. All rights reserved. Forrest, John K; Adams, David H; Popma, Jeffrey J; Reardon, Michael J; Deeb, G Michael; Yakubov, Steven J; Hermiller, James B; Huang, Jian; Skelding, Kimberly A; Lansky, Alexandra Treatment for severe symptomatic aortic stenosis has changed significantly in recent years due to advances in transcatheter aortic valve replacement (TAVR). Recent studies with the CoreValve prosthesis have demonstrated superior results compared with surgical aortic valve replacement in patients at increased risk for surgery, but there are limited data on gender-related differences in patient characteristics and outcomes with this device. We compared baseline characteristics and clinical outcomes in women and men undergoing TAVR with the CoreValve prosthesis. A total of 3,687 patients (1,708 women and 1,979 men) were included. At baseline, women tended to be slightly older and to have increased frailty, but they had fewer cardiac co-morbidities, higher left ventricular systolic function, less coronary artery disease, and fewer previous strokes. All-cause mortality was 5.9% for women and 5.8% for men at 30 days (p = 0.87) and 24.1% and 21.3%, respectively, at 1 year (p = 0.08). The incidence of stroke was 5.7% in women and 4.0% in men at 30 days (p = 0.02) and 9.3% and 7.7%, respectively, at 1 year (p = 0.05). Women had a higher incidence of bleeding, including more life-threatening bleeds, and a greater incidence of major vascular complications than men at 30 days. Device success was achieved in 86.9% of women and 86.1% of men (p = 0.50). In conclusion, although there were significant baseline differences and procedure-related complications between women and men undergoing TAVR with the CoreValve prosthesis, this analysis found no significant difference in 30-day or 1-year mortality. Vannelli, Claire; Moore, John; McLeod, Jonathan; Ceh, Dennis; Peters, Terry Cardiac valvular stenosis, prolapse and regurgitation are increasingly common conditions, particularly in an elderly population with limited potential for on-pump cardiac surgery. NeoChord©, MitraClipand numerous stent-based transcatheter aortic valve implantation (TAVI) devices provide an alternative to intrusive cardiac operations; performed while the heart is beating, these procedures require surgeons and cardiologists to learn new image-guidance based techniques. Developing these visual aids and protocols is a challenging task that benefits from sophisticated simulators. Existing models lack features needed to simulate off-pump valvular procedures: functional, dynamic valves, apical and vascular access, and user flexibility for different activation patterns such as variable heart rates and rapid pacing. We present a left ventricle phantom with these characteristics. The phantom can be used to simulate valvular repair and replacement procedures with magnetic tracking, augmented reality, fluoroscopy and ultrasound guidance. This tool serves as a platform to develop image-guidance and image processing techniques required for a range of minimally invasive cardiac interventions. The phantom mimics in vivo mitral and aortic valve motion, permitting realistic ultrasound images of these components to be acquired. It also has a physiological realistic left ventricular ejection fraction of 50%. Given its realistic imaging properties and non-biodegradable composition—silicone for tissue, water for blood—the system promises to reduce the number of animal trials required to develop image guidance applications for valvular repair and replacement. The phantom has been used in validation studies for both TAVI image-guidance techniques1, and image-based mitral valve tracking algorithms2. Merryman, W. David; Bieniek, Paul D.; Guilak, Farshid; Sacks, Michael S. There has been growing interest in the mechanobiological function of the aortic valve interstitial cell (AVIC), due to its role in valve tissue homeostasis and remodeling. In a recent study we determined the relation between diastolic loading of the AV leaflet and the resulting AVIC deformation, which was found to be substantial. However, due to the rapid loading time of the AV leaflets during closure (~0.05 s), time-dependent effects may play a role in AVIC deformation during physiological function. In the present study, we explored AVIC viscoelastic behavior using the micropipette aspiration technique. We then modeled the resulting time-length data over the 100 sec test period using a standard linear solid (SLS) model which included Boltzmann superposition. To quantify the degree of creep and stress relaxation during physiological timescales, simulations of micropipette aspiration were preformed with a valve loading time of 0.05 s and a full valve closure time of 0.3 s. The 0.05 s loading simulations suggest that, during valve closure, AVICs act elastically. During diastole, simulations revealed creep (4.65%) and stress relaxation (4.39%) over the 0.3 s physiological timescale. Simulations also indicated that if Boltzmann superposition was not used in parameter estimation, as in much of the micropipette literature, creep and stress relaxation predicted values were nearly doubled (7.92% and 7.35%, respectively). We conclude that while AVIC viscoelastic effects are negligible during valve closure, they likely contribute to the deformation time-history of AVIC deformation during diastole. PMID:19275434 ... arteries (atherosclerosis) Weakened and bulging artery (pre-existing aortic aneurysm) An aortic valve defect (bicuspid aortic valve) A ... valve, tell your doctor. If you have an aortic aneurysm, find out how often you need monitoring and ... Del Trigo, Maria; Muñoz-Garcia, Antonio J; Wijeysundera, Harindra C; Nombela-Franco, Luis; Cheema, Asim N; Gutierrez, Enrique; Serra, Vicenç; Kefer, Joelle; Amat-Santos, Ignacio J; Benitez, Luis M; Mewa, Jumana; Jiménez-Quevedo, Pilar; Alnasser, Sami; Garcia Del Blanco, Bruno; Dager, Antonio; Abdul-Jawad Altisent, Omar; Puri, Rishi; Campelo-Parada, Francisco; Dahou, Abdellaziz; Paradis, Jean-Michel; Dumont, Eric; Pibarot, Philippe; Rodés-Cabau, Josep Scarce data exist on the incidence of and factors associated with valve hemodynamic deterioration (VHD) after transcatheter aortic valve replacement (TAVR). This study sought to determine the incidence, timing, and predictors of VHD in a large cohort of patients undergoing TAVR. This multicenter registry included 1,521 patients (48% male; 80 ± 7 years of age) who underwent TAVR. Mean echocardiographic follow-up was 20 ± 13 months (minimum: 6 months). Echocardiographic examinations were performed at discharge, at 6 to 12 months, and yearly thereafter. Annualized changes in mean gradient (mm Hg/year) were calculated by dividing the difference between the mean gradient at last follow-up and the gradient at discharge by the time between examinations. VHD was defined as a ≥10 mm Hg increase in transprosthetic mean gradient during follow-up compared with discharge assessment. The overall mean annualized rate of transprosthetic gradient progression during follow-up was 0.30 ± 4.99 mm Hg/year. A total of 68 patients met criteria of VHD (incidence: 4.5% during follow-up). The absence of anticoagulation therapy at hospital discharge (p = 0.002), a valve-in-valve (TAVR in a surgical valve) procedure (p = 0.032), the use of a 23-mm valve (p = 0.016), and a greater body mass index (p = 0.001) were independent predictors of VHD. There was a mild but significant increase in transvalvular gradients over time after TAVR. The lack of anticoagulation therapy, a valve-in-valve procedure, a greater body mass index, and the use of a 23-mm transcatheter valve were associated with higher rates of VHD post-TAVR. Further prospective studies are required to determine whether a specific antithrombotic therapy post-TAVR may reduce the risk of VHD. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. Ozker, Emre; Vuran, Can; Saritas, Bülent; Türköz, Riza We describe a successful surgical treatment in a 2.5-year old boy with Loeys-Dietz syndrome, in whom we performed aortic arch and ascending aorta replacement with a valve-sparing operation (VSO) of the aortic root because of significant aortic insufficiency and dilation of the aortic root. We believe that VSO is ideal for treating young patients with aortic root aneurysm with normal or minimally diseased aortic cusps to avoid the disadvantages of prosthetic valve replacements. Cockburn, James; Dooley, Maureen; Parker, Jessica; Hill, Andrew; Hutchinson, Nevil; de Belder, Adam; Trivedi, Uday; Hildick-Smith, David Redo surgery for degenerative bioprosthetic aortic valves is associated with significant morbidity and mortality. Report results of valve-in-valve therapy (ViV-TAVI) in failed supra-annular stentless Freedom Solo (FS) bioprostheses, which are the highest risk for coronary occlusion. Six patients with FS valves (mean age 78.5 years, 50% males). Five had valvular restenosis (peak gradient 87.2 mm Hg, valve area 0.63 cm(2) ), one had severe regurgitation (AR). Median time to failure was 7 years. Patients were high risk (mean STS/Logistic EuroScore 10.6 15.8, respectively). FS valves ranged from 21 to 25 mm. Successful ViV-TAVI was achieved in 4/6 patients (67%). Of the unsuccessful cases, (patient 1 and 2 of series) patient 1 underwent BAV with simultaneous aortography which revealed left main stem occlusion. The procedure was stopped and the patient went forward for repeat surgery. Patient 2 underwent successful ViV-TAVI with a 26-mm CoreValve with a guide catheter in the left main, but on removal coronary obstruction occurred, necessitating valve snaring into the aorta. Among the successful cases, (patients 3, 4, 5, 6) the TAVIs used were CoreValve Evolut R 23 mm (n = 3), and Lotus 23 mm (n = 1). In the successful cases the peak gradient fell from 83.0 to 38.3 mm Hg. No patient was left with >1+ AR. One patient had a stroke on Day 2, with full neurological recovery. Two patients underwent semi-elective pacing for LBBB and PR >280 ms. ViV-TAVI in stentless Freedom Solo valves is high risk. The risk of coronary occlusion is high. The smallest possible prosthesis (1:1 sizing) should be used, and strategies to protect the coronary vessels must be considered. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. Schnell, Susanne; Entezari, Pegah; Mahadewia, Riti J; Malaisrie, S Chris; McCarthy, Patrick M; Collins, Jeremy D; Carr, James; Markl, Michael The aim of this study was to systematically investigate a newly developed semiautomated workflow for the analysis of aortic 4-dimensional flow MRI and its ability to detect hemodynamic differences in patients with congenitally altered aortic valve (bicuspid or quadricuspid valves) compared with tricuspid aortic valves. Four-dimensional flow MRI data were acquired in 20 patients with aortic dilatation (9 tricuspid aortic valves, 11 congenitally altered aortic valves). A semiautomated workflow was evaluated regarding interobserver variability, accuracy of net flow, regurgitant fraction and peak systolic velocity, and the ability to detect differences between cohorts. Results were compared with manual segmentation of vessel contours. Despite the significantly reduced analysis time, a good interobserver agreement was found for net flow and peak systolic velocity, and a moderate agreement was found for regurgitation. Significant differences in peak velocities in the descending aorta (P = 0.014) could be detected. Four-dimensional flow MRI-based semiautomated analysis of aortic hemodynamics can be performed with good reproducibility and accuracy. Matsumoto, Kazuhisa; Hisashi, Yosuke; Imoto, Yutaka A totally calcified ascending aorta prevents aortic crossclamping and aortotomy during aortic valve replacement, and replacement of the ascending aorta is a valid option in these cases. We describe a simple technique for calcified ascending aorta replacement using the Cavitron Ultrasonic Surgical Aspirator. This can be used in aortic endarterectomy for removal of the calcified plaque in the anastomotic part. Ott, David A.; Cooley, Denton A.; Norman, John C. A 66-year-old woman developed severe hemolysis after undergoing aortic valve replacement. A diminutive annulus and extensive calcification of the aorta precluded further surgery of the aortic root. Hemolysis was completely reversed by the implantation of a woven Dacron apicoabdominal aortic conduit incorporating a Cooley-Cutter prosthetic valve. Fractionation of stroke volume by means of a second ventricular outlet can reduce shear stresses and turbulence associated with unfavorable hemodynamic conditions, thereby successfully correcting hemolysis. Images PMID:15216312 Gessat, Michael; Altwegg, Lukas; Frauenfelder, Thomas; Plass, André; Falk, Volkmar Mechanical forces and strain induced by transcatheter aortic valve implantation are usually named as origins for postoperative left ventricular arrhythmia associated with the technique. No quantitative data has been published so far to substantiate this common belief. As a first step towards quantitative analysis of the biomechanic situation at the aortic root after transapical aortic valve implantation, we present a spline-based method for reconstruction of the implanted stent from CT images and for locally measuring the deformation of the stent. Furukawa, Nobuyuki; Scholtz, Werner; Haas, Nikolaus; Ensminger, Stephan; Gummert, Jan; Börgermann, Jochen An 81-year-old man with high-grade aortic valve stenosis and status post-coronary artery bypass grafting and supracoronary replacement of the ascending aorta was referred for transcatheter aortic valve implantation. He was in New York Heart Association class III and had dyspnea. After appropriate screening, we implanted a 29-mm SAPIEN XT valve (Edwards Lifesciences, Irvine, CA USA) through a transapical approach because of severe peripheral arterial occlusive disease. Postinterventional aortography revealed correct positioning and function of the valve and free coronary ostia but contrast extravasation in the vicinity of the interposed vascular prosthesis, resulting in severe luminal narrowing. We chose to manage the stenosis with an endovascular stent. After stenting, extravascular compression was markedly reduced, and the pressure gradient disappeared. The patient was discharged home on the 20th postoperative day. Three months later, computed tomography depicted correct positioning of both grafts. The patient's general health is good, and he is now in New York Heart Association class II. This case illustrates a complication of transcatheter aortic valve implantation specific for patients with an ascending aortic graft. Although stenting may be a good solution, as depicted by this case, self-expanding transcatheter aortic valves should be preferred in patients with ascending aortic grafts to avoid the described complication. Luo, Xiang; Wang, Xu; Li, Xuan; Wang, Xin; Xu, Fei; Liu, Mingzheng; Yu, Bing; Li, Fei; Tong, Minghui; Wang, Wei Transcatheter aortic valve implantation has become a routine procedure to treat screened inoperable or high-risk patients. In this study, we present the first outcome of echocardiographic midterm using a new second-generation transcatheter aortic valve implantation system, the J-Valve system (Jie Cheng Medical Technologies, Suzhou, China), in patients with aortic stenosis or aortic regurgitation. From July 2014 to June 2015, 21 patients with isolated aortic valve disease at high risk for open surgery received transapical transcatheter aortic valve implantation using the J-Valve system. The primary end point was a combined efficacy end point after 1 year, which included all-cause mortality after more than 30 days and failure of current therapy for aortic stenosis or aortic regurgitation requiring hospitalization for symptoms of valve-related cardiac decompensation or prosthetic heart valve dysfunction. Secondary end points were cardiovascular mortality, major stroke, and life-threatening, disabling, or major bleeding after 6 and 12 months. The mean age of the study cohort was 75.52 ± 5.22 years, the European System for Cardiac Operative Risk Evaluation II score was 11.33% ± 1.28%, and the mean logistic European System for Cardiac Operative Risk Evaluation I score was 31.13% ± 9.68%. Transcatheter aortic valve implantation with the J-Valve system was successfully performed in 19 of the 21 patients (90.5%). For patients with aortic stenosis, 12-month follow-up echocardiography demonstrated an increase in mean effective valve area from 0.62 ± 0.17 cm(2) to 1.52 ± 0.35 cm(2) and a decrease in transvalvular mean gradient from 61 ± 15 mm Hg to 18 ± 9 mm Hg. All surviving patients (n = 18) reported improvements in at least 1 of the New York Heart Association classes. The combined ratio of successful implantation and absence of adverse events in our cohort (n = 21) was 76.19%. The J-Valve system exhibits a convincing midterm performance and Maruyama, Masaki; Daimon, Masao; Kawata, Takayuki; Kasai, Takatoshi; Ichikawa, Ryoko; Miyazaki, Sakiko; Ohmura, Hirotoshi; Yamamoto, Taira; Amano, Atsushi; Daida, Hiroyuki The Trifecta valve (St Jude Medical) is a novel supra-annular aortic bioprosthesis designed to improve hemodynamic performance. We hypothesized that the Trifecta may offer better hemodynamic performance in Japanese patients, in whom the annulus is smaller, compared with Western populations. We compared the early results of hemodynamic performance between the Trifecta and the Magna (Edwards Lifescience) valves at our institution. The Trifecta was implanted in 33 patients and the Magna was implanted in 41 patients who had aortic valve disease. Postoperative echocardiography was performed just before discharge, and the mean pressure gradient (MPG), effective orifice area (EOA) index and energy loss coefficient (ELCo) index were compared between the 2 groups. The average prosthesis size was similar between the 2 groups (21.1 vs. 21.3mm). The Trifecta group had a significantly lower MPG (P=0.001) and larger EOA index and ELCo index than the Magna group (P<0.001 for both). On multivariate linear regression analysis, use of the Trifecta was the strongest independent determinant of postoperative MPG, EOA and ELCo index. The Trifecta valve provides excellent early postoperative hemodynamic performance in Japanese patients. Patients with a small annulus size relative to body size may benefit more from the Trifecta in terms of postoperative hemodynamic performance. Roberts, W C; Sullivan, M F Clinical and necropsy findings are described in 54 patients, aged 25 to 83 years (mean 53), who died within 60 days of simultaneous replacements of both mitral and aortic valves. The patients were separated into 4 groups on the basis of the presence of stenosis (with or without associated regurgitation) or pure regurgitation of each valve: 30 patients (56%) had combined mitral and aortic valve stenosis; 12 patients (22%) had mitral stenosis and pure aortic regurgitation; 8 patients (15%) had pure regurgitation of both valves; and 4 patients (7%) had pure aortic regurgitation and mitral stenosis. Necropsy examination in the 54 patients disclosed a high frequency (48%) of anatomic evidence of interference to poppet or disc movement in either the mitral or aortic valve position or both. Anatomic evidence of interference to movement of a poppet or disc in the aortic valve position was twice as common as anatomic evidence of interference to poppet or disc movement in the mitral position. Interference to poppet movement is attributable to the prosthesis's being too large for the ascending aorta or left ventricular cavity in which it resided. The ascending aorta is infrequently enlarged in patients with combined mitral and aortic valve dysfunction irrespective of whether the aortic valve is stenotic or purely regurgitant. Likewise, the left ventricular cavity is usually not dilated in patients with combined mitral and aortic valve stenosis, the most common indication for replacement of both left-sided cardiac valves. Of the 54 patients, 12 (22%) had 1 mechanical and 1 bioprosthesis inserted. It is recommended that both substitute valves should be mechanical prostheses or both should be bioprostheses. Kiramijyan, Sarkis; Magalhaes, Marco A; Koifman, Edward; Didier, Romain; Escarcega, Ricardo O; Baker, Nevin C; Negi, Smita I; Minha, Sa'ar; Torguson, Rebecca; Jiaxiang, Gai; Asch, Federico M; Wang, Zuyue; Okubagzi, Petros; Gaglia, Michael A; Ben-Dor, Itsik; Satler, Lowell F; Pichard, Augusto D; Waksman, Ron The incidence of aortic regurgitation (AR) after transcatheter aortic valve replacement (TAVR) in a self-expanding and a balloon-expandable system is controversial. This study aimed to examine the incidence and severity of post-TAVR AR with the CoreValve (CV) versus the Edwards XT Valve (XT). Baseline, procedural, and postprocedural inhospital outcomes were compared. The primary end point was the incidence of post-TAVR AR of any severity, assessed with a transthoracic echocardiogram, in the CV versus XT groups. A multivariate logistic regression analysis was completed to evaluate for correlates of the primary end point. The secondary end points included the change in severity of AR at 30-day and 1-year follow-up. A total of 223 consecutive patients (53% men, mean age 82 years) who had transfemoral TAVR with either a CV (n = 119) or XT (n = 104) were evaluated. The rates of post-TAVR AR in the groups were similar, and there was no evidence of more-than-moderate AR in either group. There were significant differences in the rates of intraprocedural balloon postdilation with the CV (17.1%) versus XT valve (5.8%; p = 0.009) and in the rates of intraprocedural implantation of a second valve-in-valve prosthesis with the CV (9.9%) versus XT valve (2.2%; p = 0.036). There were no significant differences in inhospital safety outcomes between the 2 groups. In conclusion, the incidence of post-TAVR AR is similar between the CV and the XT valve when performed by experienced operators using optimal intraprocedural strategies, as deemed appropriate, to mitigate the severity of AR. Passik, C S; Ackermann, D M; Piehler, J M; Edwards, W D A 74-year-old woman who had undergone aortic valve replacement with an Ionescu-Shiley bioprosthesis was evaluated and treated because aortic insufficiency developed after the application of the Heimlich maneuver. Pathologic examination of the explanted valve disclosed a cuspid perforation and an adjacent tear of a second cusp at its insertion into the valve strut. Patients with unexplained acute prosthetic insufficiency should be questioned as to whether the Heimlich maneuver has been previously performed. Makita, Satoru; Maruyama, Toshiyuki A 76-year-old woman with primary antiphospholipid syndrome (APS) was referred to our hospital due to severe aortic valve stenosis. We performed aortic valve replacement using a bioprosthetic valve. Her postoperative course was uneventful. She was discharged in good health on postoperative day 33. As for cardiovascular operations in APS patients, high rates have been reported of perioperative mortality and thromboembolic and bleeding events. Perioperative management of anticoagulation must be strict. Cooley, D A; Garrett, J R A new technique is described for relief of diffuse obstruction in the left ventricular outflow tract without aortic valve replacement. Left ventricular septoplasty was performed, preserving the aortic valve. The supra-valve stenosis was repaired using a Y-shaped extension of the aortotomy proximally and a pantaloon-shaped patch of woven Dacron fabric. A 10-year-old girl with "tunnel" or diffuse stenosis obtained striking relief of left ventricular hypertension by this technique. Mahr, Claudius; Chivukula, Venkat Keshav; McGah, Patrick; Prisco, Anthony R; Beckman, Jennifer A; Mokadam, Nahush A; Aliseda, Alberto This study evaluates quantitatively the impact that intermittent Aortic Valve opening has on the thrombogenicity in the aortic arch region for patients under Left Ventricular Assist Device therapy. The influence of flow through the Aortic Valve, opening once every five cardiac cycles, on the flow patterns in the ascending aortic is measured in a patient-derived CT-image-based model, after LVAD implantation. The mechanical environment of flowing platelets is investigated, by statistical treatment of outliers in Lagrangian particle tracking, and thrombogenesis metrics (platelet residence times and activation state characterized by shear stress accumulation) are compared for the cases of no Aortic Valve opening and intermittent Aortic Valve opening. All hemodynamics metrics are improved by Aortic Valve opening, even at a reduced frequency and flow rate. Residence times of platelets or microthrombi are reduced significantly by transvalvular flow, as are the shear stress history experienced and the shear stress magnitude and gradients on the aortic root endothelium. The findings of this device-neutral study support the multiple advantages of management that enables Aortic Valve opening, providing a rationale for establishing this as a standard in long-term treatment and care for advanced heart failure patients. Gilmanov, Daniyar; Farneti, Pier Andrea; Miceli, Antonio; Bevilacqua, Stefano; Glauber, Mattia The rapid development and refinement of techniques over the past decade have led to the realization that a minimally invasive approach enables aortic valve surgery to be performed with results, at the very least, equivalent to those of traditional (open) valve surgery done in experienced centres. Minimally invasive aortic valve replacement (MIAVR) has now evolved into a safe, efficient treatment option providing greater patient satisfaction and fewer complications. For rapidly ageing population of industrialized countries, aortic valve replacement (AVR) has become the most frequent heart valve surgery. However, transcatheter aortic valve implantation techniques and sutureless aortic valve prostheses recently introduced into clinical practice are challenging now the results of MIAVR in certain high surgical risk patients. Right anterior minithoracotomy results in excellent exposure and a safe conduct of AVR. The minithoracotomy is performed via the second intercostal space with a 6-7 cm long skin incision and no bone transection. After direct aortic and peripheral venous cannulation, aortic valve is exposed in a conventional manner, and further conduct of the intervention is not different from the sutureless AVR in median sternotomy. Herein, we discuss the indications, surgical technique and initial results of sutureless AVR through right anterior minithoracotomy. Zacek, Pavel; Holubec, T; Vobornik, M; Dominik, J; Takkenberg, J; Harrer, J; Vojacek, J In patients after aortic valve surgery, the quality of life is hypothesized to be influenced by the type of the valve procedure. A cross-sectional study on the postoperative quality of life was carried out in patients after aortic valve-sparing surgery (with regards to the age of the patient), Ross procedure and mechanical aortic valve replacement. Quality of life was studied in 139 patients after aortic valve surgery divided into four study groups (Y - aortic valve-sparing procedure at the age below 50 years, mean age 36.2 years; O - aortic valve-sparing procedure at the age 50 years and over, mean age 59.2 years; R - Ross procedure, mean age 37.8 years and M - mechanical aortic valve replacement at the age below 50 years, mean age 39.2 years). SF-36 Short Form and valve-specific questionnaires were mailed to the patients after 6 months or later following surgery (median 26.9 months). In SF-36, the younger aortic valve repair patients and the Ross patients scored significantly better in 4 of 4 physical subscales and in 2 of 4 mental subscales than the older aortic valve repair and mechanical valve replacement patients. In the valve-specific questionnaire; however, all 3 groups free of anticoagulation (Y, O, and R) displayed greater freedom from negative valve-related concerns. Postoperative quality of life is influenced by the type of aortic valve procedure and is negatively linked with mechanical prosthesis implantation and long-term anticoagulation. Aortic valve-sparing strategy should be considered in cases with suitable valve morphology due to favorable clinical results and beneficial impact on the long-term quality of life. Berlin, David B; Davidson, Michael J; Schoen, Frederick J We sought to evaluate the principles of disruptive innovation, defined as technology innovation that fundamentally shifts performance and utility metrics, as applied to transcatheter aortic valve implantation (TAVI). In particular, we considered implantation procedure, device design, cost, and patient population. Generally cheaper and lower performing, classical disruptive innovations are first commercialized in insignificant markets, promise lower margins, and often parasitize existing usage, representing unattractive investments for established market participants. However, despite presently high unit cost, TAVI is less invasive, treats a "new," generally high risk, patient population, and is generally done by a multidisciplinary integrated heart team. Moreover, at least in the short-term TAVI has not been lower-performing than open surgical aortic valve replacement in high-risk patients. We conclude that TAVI extends the paradigm of disruptive innovation and represents an attractive commercial opportunity space. Moreover, should the long-term performance and durability of TAVI approach that of conventional prostheses, TAVI will be an increasingly attractive commercial opportunity. Dabiri, Y; Paulson, K; Tyberg, J; Ronsky, J; Ali, I; Di Martino, E; Narine, K Bioprosthetic Aortic Valves (BAVs) do not have the serious limitations of mechanical aortic valves in terms of thrombosis. However, the lifetime of BAVs is too short, often requiring repeated surgeries. The lifetime of BAVs might be improved by using computer simulations of the structural behavior of the leaflets. The goal of this study was to develop a numerical model applicable to the optimization of durability of BAVs. The constitutive equations were derived using biaxial tensile tests. Using a Fung model, stress and strain data were computed from biaxial test data. SolidWorks was used to develop the geometry of the leaflets, and ABAQUS finite element software package was used for finite element calculations. Results showed the model is consistent with experimental observations. Reaction forces computed by the model corresponded with experimental measurements when the biaxial test was simulated. As well, the location of maximum stresses corresponded to the locations of frequent tearing of BAV leaflets. Results suggest that BAV design can be optimized with respect to durability. Lang, Pencilla; Seslija, Petar; Chu, Michael W A; Bainbridge, Daniel; Guiraudon, Gerard M; Jones, Douglas L; Peters, Terry M Transcatheter aortic valve implantation is a minimally invasive alternative to open-heart surgery for aortic stenosis in which a stent-based bioprosthetic valve is delivered into the heart on a catheter. Limited visualization during this procedure can lead to severe complications. Improved visualization can be provided by live registration of transesophageal echo (TEE) and fluoroscopy images intraoperatively. Since the TEE probe is always visible in the fluoroscopy image, it is possible to track it using fiducial-based single-perspective pose estimation. In this study, inherent probe tracking performance was assessed, and TEE to fluoroscopy registration accuracy and robustness were evaluated. Results demonstrated probe tracking errors of below 0.6 mm and 0.2°, a 2-D RMS registration error of 1.5 mm, and a tracking failure rate of below 1%. In addition to providing live registration and better accuracy and robustness compared to existing TEE probe tracking methods, this system is designed to be suitable for clinical use. It is fully automatic, requires no additional operating room hardware, does not require intraoperative calibration, maintains existing procedure and imaging workflow without modification, and can be implemented in all cardiac centers at extremely low cost. Aortic valve calcification can aggravate aortic stenoses, and it is a significant cause of sudden cardiac death. The increasing number of patients with age-related calcification is a problem in developed nations. However, the only treatment option currently available is highly invasive cardiac valve replacement. Therefore, clarification of the etiology of calcification is urgently needed to develop drug therapies and prevention methods. Recent studies have revealed that calcification is not a simple sedimentation of a mineral through a physicochemical phenomenon; various factors dynamically contribute to the mechanism. Further, we are finally beginning to understand the cellular origins of calcification, which had been unclear for a long time. Based on these findings that help to clarify potential drug targets, we expect to establish drug therapies that reduce the stress on patients. In this paper, I introduce the latest findings on cells that are most likely to contribute to calcification and on calcification-related factors that may lead to the development of drug therapies. Song, Inyoung; Ko, Sung Min; Yi, Jeong Geun; Chee, Hyun Keun; Kim, Jun Seok Objective This study investigated the morphological and functional characteristics of the aortic valve and the left ventricular (LV) systolic functional parameters and myocardial mass related to the severity of myocardial fibrosis (MF) in patients with severe aortic valve stenosis (AS). Materials and Methods We retrospectively enrolled 81 patients (48 men; mean age: 59±12 years) with severe AS who underwent transthoracic echocardiography (TTE), cardiac computed tomography (CCT), and cardiovascular magnetic resonance (CMR) within 1 month and subsequent aortic valve surgery. Degree of MF was determined on delayed contrast-enhanced CMR with visual sub-segmental analysis-based quantification and was classified into three groups (no, mild, and severe) for identifying the differences in LV function and characteristics of the aortic valve. One-way ANOVA, Chi-square test or Fisher’s exact test were used to compare variables of the three groups. Univariate multinomial logistic regression analysis was performed to determine the association between the severity of MF and variables on imaging modalities. Results Of 81 patients, 34 (42%) had MF (mild, n = 18; severe, n = 16). Aortic valve calcium volume score on CCT, aortic valve area, LV mass index, LV end-diastolic volume index on CMR, presence of mild aortic regurgitation (AR), transaortic mean pressure gradient, and peak velocity on TTE were significantly different among the three groups and were associated with severity of MF on a univariate multinomial logistic regression analysis. Aortic valve calcium grade was different (p = 0.008) among the three groups but not associated with severity of MF (p = 0.375). Conclusions A multi-imaging approach shows that severe AS with MF is significantly associated with more severe calcific AS, higher LV end-diastolic volume, higher LV mass, and higher prevalence of mild AR. PMID:28129367 Debry, Nicolas; Sudre, Arnaud; Amr, Gilles; Delhaye, Cédric; Schurtz, Guillaume; Montaigne, David; Koussa, Mohamad; Modine, Thomas We compared the outcomes of transcatheter aortic valve implantation (TAVI) in three different aortic stenosis syndromes: paradoxical low-flow low-gradient aortic stenosis (PLFLG), high-gradient aortic stenosis (HGAS), and low ejection fraction low-gradient severe aortic stenosis (LEF-LG). Outcomes for PLFLG patients after TAVI procedure are not well known. Between 2010 and 2013, patients with severe (indexed aortic valve area iAVA≤0.6 cm(2)/m(2)) symptomatic aortic stenosis were consecutively referred to our institution for TAVI because of multiple comorbidities and excessive surgical risk. About 262 patients were split into three groups as following, PLFLG: mean gradient MG≤40 mm Hg, stroke volume index SVI≤35 mL/m(2), ejection fraction EF≥55%, valvuloarterial impedance Zva>4.5 mm Hg/mL/m(2), maximal aortic jet velocity MaxV<4 m/s; MG≤40 mm Hg, MaxV<4 m/s, EF≤50%, SVI≤35 mL/m(2); and HGAS: MaxV>4 m/s, MG>40 mm Hg, EF>55%. The primary endpoint of our study was to evaluate mid-term global and cardiovascular mortalities; secondary endpoints included recommended VARC-2 variables. PLFLG (n = 31) mid-term survival was similar to HGAS (n = 172) (mean follow-up = 13.2 months [4.6-26]). Conversely LEF-LG patients (n = 59) displayed significant higher rates of all-cause (P = 0.01) and cardiovascular mortalities (P = 0.05). Postprocedural outcomes (VARC-2 criteria) were similar in the PLFLG and HGAS groups except regarding major bleeding (P = 0.02), while the LEF-LG group had more congestive heart failure and a higher BNP before discharge (both P < 0.001) than the other groups. 30-days deaths were significantly more frequent in LEF-LG and PLFLG in comparison to HGAS (P = 0.03). As opposed to LEF-LG patients, mid-term prognosis after TAVI procedure in PLFLG patients is similar to HGAS patients despite higher perioperative mortality. © 2015 Wiley Periodicals, Inc. Benito-González, Tomás; Gualis, Javier; Pérez de Prado, Armando; Cuellas, Carlos; Fernandez-Vazquez, Felipe Significant periprosthetic aortic regurgitation after transcatheter aortic valve implantation has become a major concern of this technique given its association with impaired survival. We report the successful closure of such defect using a vascular occlusion device with the creation of an arterio-arterial loop to gain enough support to advance the delivery sheath into de the left ventricle. PMID:28275491 Brodt, Jessica; Vladinov, Greta; Castillo-Pedraza, Catalina; Cooper, Lebron; Maratea, Edward Cerebral oxygen saturation (rSO2) is a non-invasive monitor used to monitor cerebral oxygen balance and perfusion. Decreases in rSO2 >20 % from baseline have been associated with cerebral ischemia and increased perioperative morbidity. During transcatheter aortic valve replacement (TAVR), hemodynamic manipulation with ventricular pacing up to 180 beats per minute is necessary for valve deployment. The magnitude and duration of rSO2 change during this manipulation is unclear. In this small case series, changes in rSO2 in patients undergoing TAVR are investigated. Ten ASA IV patients undergoing TAVR with general anesthesia at a university hospital were prospectively observed. Cerebral oximetry values were analyzed at four points: pre-procedure (baseline), after tracheal intubation, during valve deployment, and at procedure end. Baseline rSO2 values were 54.5 ± 6.9 %. After induction of general anesthesia, rSO2 increased to a mean of 66.0 ± 6.7 %. During valve deployment, the mean rSO2 decreased <20 % below baseline to 48.5 ± 13.4 %. In two patients, rSO2 decreased >20 % of baseline. Cerebral oxygenation returned to post-induction values in all patients 13 ± 10 min after valve deployment. At procedure end, the mean rSO2 was 67.6 ± 8.1 %. As expected, rapid ventricular pacing resulting in the desired decrease in cardiac output during valve deployment was associated with a significant decrease in rSO2 compared to post-induction values. However, despite increased post-induction values in all patients, whether related to increased inspired oxygen fraction or reduced cerebral oxygen consumption under anesthesia, two patients experienced a significant decrease in rSO2 compared to baseline. Recovery to baseline was not immediate, and took up to 20 min in three patients. Furthermore, baseline rSO2 in this population was at the lower limit of the published normal range. Significant cerebral desaturation during valve deployment may potentially be limited Ribeiro, Gustavo S; Melo, Rosangela D; Deresz, Luís F; Dal Lago, Pedro; Pontes, Mauro Rn; Karsten, Marlus Background Aortic stenosis is a valvular heart disease characterised by fixed obstruction of the left ventricular outflow. It can be managed by surgical aortic valve replacement (sAVR) or transcatheter aortic valve implantation (TAVI). This review aimed to describe the evidence supporting a cardiac rehabilitation programme on functional capacity and quality of life in aortic stenosis patients after sAVR or TAVI. Methods The search was conducted on multiple databases from January to March 2016. All studies were eligible that evaluated the effects of a post-interventional cardiac rehabilitation programme in aortic stenosis patients. The methodological quality was assessed using the PEDro scale. Meta-analysis was performed separately by procedure and between procedures. The walked distance during the six-minute walk test (6MWD) and Barthel index were evaluated. The analysis was conducted in Review Manager. Results Five studies were included (292 TAVI and 570 sAVR patients). The meta-analysis showed that a cardiac rehabilitation programme was associated with a significant improvement in 6MWD (0.69 (0.47, 0.91); P < 0.001) and Barthel index (0.80 (0.29, 1.30); P = 0.002) after TAVI and 6MWD (0.79 (0.43, 1.15); P < 0.001) and Barthel index (0.93 (0.67, 1.18); P < 0.001) after sAVR. In addition, the meta-analysis showed that the cardiac rehabilitation programme promoted a similar gain in 6MWD (4.28% (-12.73, 21.29); P = 0.62) and Barthel index (-1.52 points (-4.81, 1.76); P = 0.36) after sAVR or TAVI. Conclusions The cardiac rehabilitation programme improved the functional capacity and quality of life in aortic stenosis patients. Patients who underwent TAVI benefitted with a cardiac rehabilitation programme similar to sAVR patients. da Costa, Francisco Diniz Affonso; Colatusso, Daniele de Fátima Fornazari; da Costa, Ana Claudia Brenner Affonso; Balbi Filho, Eduardo Mendel; Cavicchioli, Vinicius Nesi; Lopes, Sergio Augusto Veiga; Ferreira, Andrea Dumsch de Aragon; Collatusso, Claudinei Introduction Due to late complications associated with the use of conventional prosthetic heart valves, several centers have advocated aortic valve repair and/or valve sparing aortic root replacement for patients with aortic valve insufficiency, in order to enhance late survival and minimize adverse postoperative events. Methods From March/2012 thru March 2015, 37 patients consecutively underwent conservative operations of the aortic valve and/or aortic root. Mean age was 48±16 years and 81% were males. The aortic valve was bicuspid in 54% and tricuspid in the remaining. All were operated with the aid of intraoperative transesophageal echocardiography. Surgical techniques consisted of replacing the aortic root with a Dacron graft whenever it was dilated or aneurysmatic, using either the remodeling or the reimplantation technique, besides correcting leaflet prolapse when present. Patients were sequentially evaluated with clinical and echocardiographic studies and mean follow-up time was 16±5 months. Results Thirty-day mortality was 2.7%. In addition there were two late deaths, with late survival being 85% (CI 95% - 68%-95%) at two years. Two patients were reoperated due to primary structural valve failure. Freedom from reoperation or from primary structural valve failure was 90% (CI 95% - 66%-97%) and 91% (CI 95% - 69%-97%) at 2 years, respectively. During clinical follow-up up to 3 years, there were no cases of thromboembolism, hemorrhage or endocarditis. Conclusions Although this represents an initial series, these data demonstrates that aortic valve repair and/or valve sparing aortic root surgery can be performed with satisfactory immediate and short-term results. PMID:27556321 Assessment of valve haemodynamics, reverse ventricular remodelling and myocardial fibrosis following transcatheter aortic valve implantation compared to surgical aortic valve replacement: a cardiovascular magnetic resonance study Fairbairn, Timothy A; Steadman, Christopher D; Mather, Adam N; Motwani, Manish; Blackman, Daniel J; Plein, Sven; McCann, Gerry P; Greenwood, John P Objective To compare the effects of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) on aortic valve haemodynamics, ventricular reverse remodelling and myocardial fibrosis (MF) by cardiovascular magnetic resonance (CMR) imaging. Design A 1.5 T CMR scan was performed preoperatively and 6 months postoperatively. Setting University hospitals of Leeds and Leicester, UK. Patients 50 (25 TAVI, 25 SAVR; age 77±8 years) high-risk severe symptomatic aortic stenosis (AS) patients. Main outcome measures Valve haemodynamics, ventricular volumes, ejection fraction (EF), mass and MF. Results Patients were matched for gender and AS severity but not for age (80±6 vs 73±7 years, p=0.001) or EuroSCORE (22±14 vs 7±3, p<0.001). Aortic valve mean pressure gradient decreased to a greater degree post-TAVI compared to SAVR (21±8 mm Hg vs 35±13 mm Hg, p=0.017). Aortic regurgitation reduced by 8% in both groups, only reaching statistical significance for TAVI (p=0.003). TAVI and SAVR improved (p<0.05) left ventricular (LV) end-systolic volumes (46±18 ml/m2 vs 41±17 ml/m2; 44±22 ml/m2 vs32±6 ml/m2) and mass (83±20 g/m2 vs 65±15 g/m2; 74±11 g/m2 vs 59±8 g/m2). SAVR reduced end-diastolic volumes (92±19 ml/m2 vs 74±12 ml/m2, p<0.001) and TAVI increased EF (52±12% vs 56±10%, p=0.01). MF reduced post-TAVI (10.9±6% vs 8.5±5%, p=0.03) but not post-SAVR (4.2±2% vs 4.1±2%, p=0.98). Myocardial scar (p≤0.01) and baseline ventricular volumes (p<0.001) were the major predictors of reverse remodelling. Conclusions TAVI was comparable to SAVR at LV reverse remodelling and superior at reducing the valvular pressure gradient and MF. Future work should assess the prognostic importance of reverse remodelling and fibrosis post-TAVI to aid patient selection. PMID:23749779 Marrufo, Oscar; Solis-Najera, Sergio; Pibarot, Philippe; Kadem, Lyes; Kesharvarz-Motamed, Zahra; Rodriguez, Alfredo O.; Garcia, Julio Aortic valve morphology and phenotype may alter the aortic wall structure and its normal flow hemodynamics. However, the relationship between altered flow patterns and progression of wall pathology is often not fully understood in patients with aortic coartation and needs larger experimental work. In this study, we introduced a compatible experimental setup with magnetic resonance imaging (MRI) using a realistic aortic coarctation (AoCo) silicon model which can replicate physiological flow conditions (pressure, flow-wave, and systemic load). We evaluated the aortic valve hemodynamics of a normal tricuspid valve and a stenotic bicuspid valve using valve effective orifice area (EOA), peak and mean transvalvular pressure gradient (TPG). AoCo severity was assessed by the AoCo pressure gradient. For the tricuspid valve we obtained an EOA = 1.89 cm2, a peak TPG = 10 mmHg, and a mean TPG = 5 mmHg. For the bicuspid valve we obtained an EOA = 1.03 cm2, a peak TPG = 37 mmHg and a mean TPG = 13 mmHg. Furthermore, AoCo with tricuspid valve led to a peak AoCo pressure gradient (PG) = 11 mmHg and a mean PG = 5 mmHg. AoCo with bicuspid valve led to a peak PG = 6 mmHg and a mean PG = 3 mmHg. Aortic flow reattachment was more evident in presence of bicuspid valve and helical flow was present in all cases. This study showed that silicon prototyping in combination with MRI velocity measurements could successfully be used to assess hemodynamic effects of aortic valve morphology in aortic coarctation flow. Guauque-Olarte, Sandra; Droit, Arnaud; Tremblay-Marchand, Joël; Gaudreault, Nathalie; Kalavrouziotis, Dimitri; Dagenais, Francois; Seidman, Jonathan G; Body, Simon C; Pibarot, Philippe; Mathieu, Patrick; Bossé, Yohan The molecular mechanisms leading to premature development of aortic valve stenosis (AS) in individuals with a bicuspid aortic valve are unknown. The objective of this study was to identify genes differentially expressed between calcified bicuspid aortic valves (BAVc) and tricuspid valves with (TAVc) and without (TAVn) AS using RNA sequencing (RNA-Seq). We collected 10 human BAVc and nine TAVc from men who underwent primary aortic valve replacement. Eight TAVn were obtained from men who underwent heart transplantation. mRNA levels were measured by RNA-Seq and compared between valve groups. Two genes were upregulated, and none were downregulated in BAVc compared with TAVc, suggesting a similar gene expression response to AS in individuals with bicuspid and tricuspid valves. There were 462 genes upregulated and 282 downregulated in BAVc compared with TAVn. In TAVc compared with TAVn, 329 genes were up- and 170 were downregulated. A total of 273 upregulated and 147 downregulated genes were concordantly altered between BAVc vs. TAVn and TAVc vs. TAVn, which represent 56 and 84% of significant genes in the first and second comparisons, respectively. This indicates that extra genes and pathways were altered in BAVc. Shared pathways between calcified (BAVc and TAVc) and normal (TAVn) aortic valves were also more extensively altered in BAVc. The top pathway enriched for genes differentially expressed in calcified compared with normal valves was fibrosis, which support the remodeling process as a therapeutic target. These findings are relevant to understand the molecular basis of AS in patients with bicuspid and tricuspid valves. Takamatsu, Masanori; Hirotani, Takashi; Ohtsubo, Satoshi; Saito, Sumikatsu; Takeuchi, Shigeyuki; Hasegawa, Tasuku; Endo, Ayaka; Yamasaki, Yu; Hayashida, Kentaro A 67-year-old man on chronic hemodialysis was admitted with worsening congestive heart failure due to critical aortic stenosis. Echocardiography showed severe aortic stenosis with a valve area of 0.67 cm2 and an ejection fraction of 0.31. Cardiac catheterization revealed severe pulmonary hypertension with pulmonary artery pressures of 62/32 mmHg. In the middle of cardiac catheterization, the systolic pressure declined to 60 mmHg due to cardiogenic shock. Dopamine hydrochloride and dobutamine hydrochloride infusions were necessary to maintain a systolic pressure greater than 80 mmHg. Balloon aortic valvuloplasty was urgently performed. The patient's symptoms rapidly resolved except for angina on exertion. One month later, elective aortic valve replacement was performed. The postoperative course was uneventful and the he was discharged on the 60th postoperative day. A follow-up echocardiogram 6 months postoperatively revealed normal prosthetic valve function and an ejection fraction of 0.6. Kokubo, Hiroki; Miyagawa-Tomita, Sachiko; Nakashima, Yasumi; Kume, Tsutomu; Yoshizumi, Masao; Nakanishi, Toshio; Saga, Yumiko Acquired heart diseases, such as valve disease, are major causes of human morbidity and mortality. However, the pathological mechanisms underlying these diseases are largely unknown. Our aim is to identify the role of the hairy and enhancer of split-related (Hesr)-2 gene in the adult heart. Echocardiography detected heart dysfunctions indicative of aortic valve anomalies, stenosis, and regurgitation, in ≈59% of >12-month-old Hesr2 knockout survivor mice. Morphological and histological analyses revealed thickened semilunar valves with increased fibrotic areas, indicating that sclerotic degeneration of valves is the main cause of aortic valve disease. The expression of osteogenic genes, such as osteopontin and sclerostin, were upregulated in the mutants, and the overexpression of sclerostin in endothelial cells resulted in thickened semilunar valves with increased fibrotic areas, similar to that seen in the Hesr2 knockout mice, suggesting that Hesr2 can regulate osteogenic gene expression in valves. Reduced left ventricular function, which may be caused by increased ventricular interstitial fibrosis, and enlarged myocardial cell size without ventricular wall thickening were found in both aortic valve stenosis/regurgitation-positive (33%) and aortic valve stenosis/regurgitation-negative (38%) subpopulations in 12-month-old survivor mice. Dilated left ventricular internal dimensions were specifically detected in the aortic valve stenosis/regurgitation-positive subpopulation, thus suggesting that the degeneration of cardiomyocytes is influenced by irregular hemodynamics. These data revealed that survivor mice lacking the Hesr2 gene exhibit fibrosis in the aortic valve and ventricle in adulthood, thus suggesting that Hesr2 plays an important role in maintaining the homeostasis of the aortic valve and ventricle. Hutcheson, Joshua D.; Aikawa, Elena; Merryman, W. David Calcific aortic valve disease (CAVD) is a major contributor to cardiovascular morbidity and mortality and, given its association with age, the prevalence of CAVD is expected to continue to rise as global life expectancy increases. No drug strategies currently exist to prevent or treat CAVD. Given that valve replacement is the only available clinical option, patients often cope with a deteriorating quality of life until diminished valve function demands intervention. The recognition that CAVD results from active cellular mechanisms suggests that the underlying pathways might be targeted to treat the condition. However, no such therapeutic strategy has been successfully developed to date. One hope was that drugs already used to treat vascular complications might also improve CAVD outcomes, but the mechanisms of CAVD progression and the desired therapeutic outcomes are often different from those of vascular diseases. We, therefore, discuss the benchmarks that must be met by a CAVD treatment approach, and highlight advances in the understanding of CAVD mechanisms to identify potential novel therapeutic targets. PMID:24445487 Cloutier, G; Lemire, F; Durand, L G; Latour, Y; Jarry, M; Solignac, A; Langlois, Y E Amplitude distributions of Doppler spectrograms were characterized in a group of 22 patients having no aortic pressure gradient and another group of 26 patients having a stenotic aortic valve. Specifically, for each patient, the ratios of the mean amplitude in three normalized frequency bands (low, middle and high) to the mean amplitude of the Doppler spectrogram computed in selected portions of the systolic period were considered. Pulsed-wave Doppler spectrograms were recorded by positioning the sample volume in the left ventricular outflow tract, approximately 1 cm below the aortic valve. Statistically significant differences were found between the middle (p = 0.041) and high (p = 0.028) frequency bands of Doppler signals recorded from the two groups of patients. The differences observed are believed to be attributed to blood flow eddies generated below the stenotic aortic heart valve and to changes in blood flow orientation. Picardo, Preeti Jane; Khariong, Peter Daniel S; Hajong, Debobratta; Naku, Narang; Anand, Madhur; Sharma, Girish; Singh, K Lenish Introduction Aortic valve sclerosis has been shown to be associated with increased incidence, chances of developing myocardial infarction and even death. The epidemiological risk factors causing calcification of aortic valves have also been found to cause atherosclerosis. Aim To analyse the epidemiological risk factors causing aortic valve sclerosis which have been studied in details and analysed to see whether they cause any significant increase in the incidence of cardiovascular events. Materials and Methods This prospective case-control study was conducted between 1st Jan 2015 to 31st Dec 2015 in NEIGRIHMS hospital and data for age, gender, socioeconomic status, hypertension, diabetes, tobacco use, Body Mass Iindex (BMI), cholesterol levels, Electrocardiography (ECG) changes and Ejection Fraction (EF) were collected and analysed by using SPSS software version 22. Results Hypertension, diabetes, weight, BMI, hyperglycaemia and hyperlipidemia were not found to be significantly associated with aortic valve sclerosis in patients presenting with acute coronary syndromes. The presence of aortic valve sclerosis was also not associated with increased risk of cardiovascular mortality and morbidity. Conclusion The risk factors for atherosclerosis were found to be associated with the presence of aortic valve sclerosis more in the control group and hence finding of a sclerosed aortic valve in the apparent normal population might identify those persons at increased risk of developing coronary artery disease and appropriate preventive measures should be taken before the disease sets in. PMID:28208902 Martin, Caitlin; Sun, Wei Transcatheter aortic valve (TAV) intervention is now the standard-of-care treatment for inoperable patients and a viable alternative treatment option for high-risk patients with symptomatic aortic stenosis. While the procedure is associated with lower operative risk and shorter recovery times than traditional surgical aortic valve (SAV) replacement, TAV intervention is still not considered for lower-risk patients due in part to concerns about device durability. It is well known that bioprosthetic SAVs have limited durability, and TAVs are generally assumed to have even worse durability, yet there is little long-term data to confirm this suspicion. In this study, TAV and SAV leaflet fatigue due to cyclic loading was investigated through finite element analysis by implementing a computational soft tissue fatigue damage model to describe the behavior of the pericardial leaflets. Under identical loading conditions and with identical leaflet tissue properties, the TAV leaflets sustained higher stresses, strains, and fatigue damage compared to the SAV leaflets. The simulation results suggest that the durability of TAVs may be significantly reduced compared to SAVs to about 7.8 years. The developed computational framework may be useful in optimizing TAV design parameters to improve leaflet durability, and assessing the effects of underexpanded, elliptical, or non-uniformly expanded stent deployment on TAV durability. Copyright © 2015 Elsevier Ltd. All rights reserved. D'Ancona, Giuseppe; Agma, Hüseyin U; Ince, Hüseyin; El-Achkar, Gihan; Dißmann, Martin; Ortak, Jasmin; Kische, Stephan We present our single center experience with the direct flow medical (DFM) prosthesis addressing the impact of native aortic valve (AV) calcification degree on outcomes. The DFM® has been introduced for transcatheter aortic valve implantation (TAVI). The valve has a nonmetallic and inflatable support structure. Patients were divided in two groups according to preoperative cardiac computed tomography (CT): group I moderate calcification and group II heavy calcification of the total AV area. We evaluated 118 patients: 53 (45%) group I and 65 (55%) group II. Preoperative trans-AV gradient and calcification extension across the aortic unit were significantly higher in group II (P = 0.008 and P < 0.0001). CT perimeter derived annular diameter (group I 24.7 ± 2.1 mm vs. group II 24.8 ± 1.9; P = 0.6) and implanted prosthesis size (group I 26.1 ± 1.5 mm vs. group II 25.7 ± 1.5; P = 0.1) were similar. Hemodynamics were similar: mean gradient 16.1 ± 5.9 mm Hg (group I) vs. 17.3 ± 6.5 mm Hg (group II) (P = 0.3). Total aortic regurgitation (AR) was mild in 5.7% in group I and 20% in group II (P = 0.03). None developed moderate/severe AR. Heavy AV calcification was the sole independent determinant for mild regurgitation (P = 0.02; OR = 7; 95% CI: 1.2-37.6). Follow-up (289 days; 40-760 days) estimated survival was 88.1% (group I) and 93.8% (group II) (P = 0.3). Independent of AV calcification degree, adequate sizing and implantation can be achieved with the DFM®. Although higher burden of calcification increases the rate of mild AR, no patient developed moderate and severe AR. Short-term estimated survival was not influenced by calcification degree. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. Adamo, Luigi; Braverman, Alan C The bicuspid aortic valve (BAV) affects 1-2% of the population and may be associated with important valvular disease and an increased risk of aortic root and/or ascending aortic aneurysm and dissection. BAV aortic aneurysm and dissection occur earlier in life than when these disorders are associated with a tricuspid aortic valve (TAV). Alterations in the aortic media and differences in aortic elastic properties and wall stress also accompany BAV aortopathy. With appropriate follow-up and timely surgery, population studies have documented a survival rate for patients with BAV no different from age-matched controls. Guidelines have previously recommended prophylactic aortic surgery at a smaller aortic aneurysm size for patients with BAV compared with aneurysms in patients with a TAV. Recent guidelines have presented differing indications regarding the appropriate timing of prophylactic surgery for BAV aneurysms, giving the recommendation for surgery when the aortic root and/or ascending aortic exceeds 5.5 cm (unless certain factors are present), the same size for which TAV-associated aortic aneurysm surgery is recommended. We review the pathophysiology of BAV aortopathy, the clinical history of BAV ascending aortic disease, areas of uncertainty and make a case for a patient-centered, individualised decision regarding the optimal timing of aortic aneurysm surgery in BAV disease. Farah, Fahmi J. Primary malignant cardiac lymphomas associated with grafts are extremely rare: to our knowledge, only 6 cases of prosthesis-associated B-cell lymphoma have been reported. Ours is the first report of recurrent diffuse large B-cell lymphoma associated with aortic valve allografts. We treated a 60-year-old man who presented in early 2007 with aortic valve endocarditis. He underwent aortic valve replacement with an allograft; the resected native valve showed active endocarditis without tumor. In January 2011, the patient underwent repeat aortic valve replacement because of symptomatic aortic regurgitation. The explanted valve specimen displayed diffuse large B-cell lymphoma. In September 2011, the patient presented with fever and a mass around the aortic valve. He died in January 2012. On autopsy, the explanted replacement valve displayed recurrent diffuse large B-cell lymphoma. The recurrent lymphoma on a new graft leads us to believe that this tumor is more aggressive than had been thought. We propose early systemic chemotherapy, in addition to tumor resection, for the possibility of a better prognosis. We discuss our patient's case and review the relevant medical literature. PMID:25425992 Sapp, Matthew C; Krishnamurthy, Varun K; Puperi, Daniel S; Bhatnagar, Saheba; Fatora, Gabrielle; Mutyala, Neelesh; Grande-Allen, K Jane Tissue oxygenation often plays a significant role in disease and is an essential design consideration for tissue engineering. Here, oxygen diffusion profiles of porcine aortic and mitral valve leaflets were determined using an oxygen diffusion chamber in conjunction with computational models. Results from these studies revealed the differences between aortic and mitral valve leaflet diffusion profiles and suggested that diffusion alone was insufficient for normal oxygen delivery in mitral valves. During fibrotic valve disease, leaflet thickening due to abnormal extracellular matrix is likely to reduce regional oxygen availability. To assess the impact of low oxygen levels on valve behaviour, whole leaflet organ cultures were created to induce leaflet hypoxia. These studies revealed a loss of layer stratification and elevated levels of hypoxia inducible factor 1-alpha in both aortic and mitral valve hypoxic groups. Mitral valves also exhibited altered expression of angiogenic factors in response to low oxygen environments when compared with normoxic groups. Hypoxia affected aortic and mitral valves differently, and mitral valves appeared to show a stenotic, rheumatic phenotype accompanied by significant cell death. These results indicate that hypoxia could be a factor in mid to late valve disease progression, especially with the reduction in chondromodulin-1 expression shown by hypoxic mitral valves. © 2016 The Author(s). Wang, Jun; Wang, Ying; Gu, Weidong; Ni, Buqing; Sun, Haoliang; Yu, Tong; Gu, Wanjun; Chen, Liang; Shao, Yongfeng RNA sequencing (RNA-seq) has revolutionary roles in transcriptome identification and quantification of different types of tissues and cells in many organisms. Although numerous RNA-seq data derived from many types of human tissues and cell lines, little is known on the transcriptome repertoire of human aortic valve. In this study, we sequenced the total RNA prepared from two calcified human aortic valves and reported the whole transcriptome of human aortic valve. Integrating RNA-seq data of 13 human tissues from Human Body Map 2 Project, we constructed a transcriptome repertoire of human tissues, including 19,505 protein-coding genes and 4,948 long intergenic noncoding RNAs (lincRNAs). Among them, 263 lincRNAs were identified as novel noncoding transcripts in our data. By comparing transcriptome data among different human tissues, we observed substantial tissue specificity of RNA transcripts, both protein-coding genes and lincRNAs, in human aortic valve. Further analysis revealed that aortic valve-specific lincRNAs were more likely to be recently derived from repetitive elements in the primate lineage, but were less likely to be conserved at the nucleotide level. Expression profiling analysis showed significant lower expression levels of aortic valve-specific protein-coding genes and lincRNA genes, when compared with genes that were universally expressed in various tissues. Isoform-level expression analysis also showed that a majority of mRNA genes had a major isoform expressed in the human aortic valve. To our knowledge, this is the first comparative transcriptome analysis between human aortic valve and other human tissues. Our results are helpful to understand the transcriptome diversity of human tissues and the underlying mechanisms that drive tissue specificity of protein-coding genes and lincRNAs in human aortic valve. PMID:27493474 Wijeysundera, Harindra C; Li, Lindsay; Braga, Vevien; Pazhaniappan, Nandhaa; Pardhan, Anar M; Lian, Dana; Leeksma, Aric; Peterson, Ben; Cohen, Eric A; Forsey, Anne; Kingsbury, Kori J Objective Transcatheter aortic valve implantation (TAVI) is generally more expensive than surgical aortic valve replacement (SAVR) due to the high cost of the device. Our objective was to understand the patient and procedural drivers of cumulative healthcare costs during the index hospitalisation for these procedures. Design All patients undergoing TAVI, isolated SAVR or combined SAVR+coronary artery bypass grafting (CABG) at 7 hospitals in Ontario, Canada were identified during the fiscal year 2012–2013. Data were obtained from a prospective registry. Cumulative healthcare costs during the episode of care were determined using microcosting. To identify drivers of healthcare costs, multivariable hierarchical generalised linear models with a logarithmic link and γ distribution were developed for TAVI, SAVR and SAVR+CABG separately. Results Our cohort consisted of 1310 patients with aortic stenosis, of whom 585 underwent isolated SAVR, 518 had SAVR+CABG and 207 underwent TAVI. The median costs for the index hospitalisation for isolated SAVR were $21 811 (IQR $18 148–$30 498), while those for SAVR+CABG were $27 256 (IQR $21 741–$39 000), compared with $42 742 (IQR $37 295–$56 196) for TAVI. For SAVR, the major patient-level drivers of costs were age >75 years, renal dysfunction and active endocarditis. For TAVI, chronic lung disease was a major patient-level driver. Procedural drivers of cost for TAVI included a non-transfemoral approach. A prolonged intensive care unit stay was associated with increased costs for all procedures. Conclusions We found wide variation in healthcare costs for SAVR compared with TAVI, with different patient-level drivers as well as potentially modifiable procedural factors. These highlight areas of further study to optimise healthcare delivery. PMID:27621832 Koh, Ezra Y; Lam, Kayan Y; Bindraban, Navin R; Cocchieri, Riccardo; Planken, R Nils; Koch, Karel T; Baan, Jan; de Mol, Bas A; Marquering, Henk A To determine whether the location of aortic valve calcium (AVC) influences the location of paravalvular regurgitation (PR). PR is an adverse effect of transcatheter aortic valve implantation (TAVI) with a negative effect on long-term patient survival. The relationship between AVC and the occurrence of PR has been documented. However, the relationship between the distribution of AVC and the location of PR is still sparsely studied. The purpose of this study was to correlate severity and location of AVC with PR in patients treated with TAVI. Fifty-six consecutive patients who underwent transaortic or transapical TAVI and had preoperative computed tomography scans were included in this retrospective study. The volume, mass and location of AVC was determined and compared between patients with and without PR using a non-parametric t-test. Postoperative echocardiography was performed to determine the presence and location of PR, which was associated with the cusp with highest AVC using a χ(2) test. Valve deployment was successful in all 56 patients. PR was present in 38 patients (68%) after TAVI. There was a non-significantly higher volume of AVC in the PR group [214 (70-418) vs 371 (254-606) cm(3), P = 0.15]. AVC mass was significantly higher in patients with PR than in patients without PR [282 (188-421) vs 142 (48-259) mg, respectively, P = 0.043]. The location of PR was determined in 36 of these patients. Of these 36 patients, PR occurred at the cusp with the highest AVC in 20 patients (56%, χ(2) P = 0.030). In our population, PR was associated with greater AVC mass. Moreover, the location of PR was associated with the cusp with the highest amount of AVC. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. Harrison, Oliver J.; Moorjani, Narain; Torrens, Christopher; Ohri, Sunil K.; Cagampang, Felino R. Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality and predisposes patients to life-threatening aortic complications including aortic aneurysm. Quantitative real-time reverse transcription PCR (qRT-PCR) is one of the most commonly used methods to investigate underlying molecular mechanisms involved in aortopathy. The accuracy of the gene expression data is dependent on normalization by appropriate housekeeping (HK) genes, whose expression should remain constant regardless of aortic valve morphology, aortic diameter and other factors associated with aortopathy. Here, we identified an appropriate set of HK genes to be used as endogenous reference for quantifying gene expression in ascending aortic tissue using a spin column-based RNA extraction method. Ascending aortic biopsies were collected intra-operatively from patients undergoing aortic valve and/or ascending aortic surgery. These patients had BAV or tricuspid aortic valve (TAV), and the aortas were either dilated (≥4.5cm) or undilated. The cohort had an even distribution of gender, valve disease and hypertension. The expression stability of 12 reference genes were investigated (ATP5B, ACTB, B2M, CYC1, EIF4A2, GAPDH, SDHA, RPL13A, TOP1, UBC, YWHAZ, and 18S) using geNorm software. The most stable HK genes were found to be GAPDH, UBC and ACTB. Both GAPDH and UBC demonstrated relative stability regardless of valve morphology, aortic diameter, gender and age. The expression of B2M and SDHA were found to be the least stable HK genes. We propose the use of GAPDH, UBC and ACTB as reference genes for gene expression studies of BAV aortopathy using ascending aortic tissue. PMID:27727313 Harrison, Oliver J; Moorjani, Narain; Torrens, Christopher; Ohri, Sunil K; Cagampang, Felino R Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality and predisposes patients to life-threatening aortic complications including aortic aneurysm. Quantitative real-time reverse transcription PCR (qRT-PCR) is one of the most commonly used methods to investigate underlying molecular mechanisms involved in aortopathy. The accuracy of the gene expression data is dependent on normalization by appropriate housekeeping (HK) genes, whose expression should remain constant regardless of aortic valve morphology, aortic diameter and other factors associated with aortopathy. Here, we identified an appropriate set of HK genes to be used as endogenous reference for quantifying gene expression in ascending aortic tissue using a spin column-based RNA extraction method. Ascending aortic biopsies were collected intra-operatively from patients undergoing aortic valve and/or ascending aortic surgery. These patients had BAV or tricuspid aortic valve (TAV), and the aortas were either dilated (≥4.5cm) or undilated. The cohort had an even distribution of gender, valve disease and hypertension. The expression stability of 12 reference genes were investigated (ATP5B, ACTB, B2M, CYC1, EIF4A2, GAPDH, SDHA, RPL13A, TOP1, UBC, YWHAZ, and 18S) using geNorm software. The most stable HK genes were found to be GAPDH, UBC and ACTB. Both GAPDH and UBC demonstrated relative stability regardless of valve morphology, aortic diameter, gender and age. The expression of B2M and SDHA were found to be the least stable HK genes. We propose the use of GAPDH, UBC and ACTB as reference genes for gene expression studies of BAV aortopathy using ascending aortic tissue. Hosseinpour, Amir-Reza; González-Calle, Antonio; Adsuar-Gómez, Alejandro; Santos-deSoto, José Aortic valve reconstruction with fixed pericardium may occasionally be very useful when treating children with aortic valve disease. This is because diseased aortic valves in children are sometimes too dysmorphic for simple repair without the addition of material, their annulus may be too small for a prosthesis, and the Ross operation may be precluded due to other congenital anomalies such as pulmonary valvar or coronary malformations. Such reconstruction is usually technically demanding and requires much precision. We describe a simple alternative method, which we have carried out in 3 patients, aged 1 week, 3 years and 12 years, respectively, with good early results. PMID:23343835 Kutschka, I; Skorpil, J; El Essawi, A; Hajek, T; Harringer, W Minimized perfusion circuits (MPC) were found to reduce side effects of standard extracorporeal circulation (ECC). We evaluated the safety and efficacy of the ROCsafe MPC for aortic valve and aortic root surgery. One hundred and seventy patients were randomized for surgery using either MPC [n = 85, 30 female/55 male, mean age: 69.8 +/- 11.8 years; aortic valve replacement (AVR): n = 40; AVR + coronary artery bypass graft (CABG): n = 31; David operation: n = 3; aortic root replacement (ARR): n = 11] or ECC [n = 85, 29 female/56 male, mean age: 67.7 +/- 9.5 years; AVR: n = 39; AVR+CABG: n = 35, David operation: n = 2; ARR: n = 9]. Neurological status, length of ICU stay, C-reactive protein (CRP), blood count, transfusion requirements and bleeding volume were analyzed. The MPC system provided ultrasound-controlled de-airing. A small roller pump and a flexible reservoir were used for left ventricular venting. As a control, we used a standard ECC with cardiotomy suction and hard-shell reservoir. Cross-clamp time (MPC: 76.5 +/- 29.5; ECC: 79.0 +/- 34.0 min) and bypass time (MPC: 103.0 +/- 37.9; ECC: 106.9 +/- 44.9 min) were comparable between groups. Transfusion requirements (red blood cells: MPC: 1.5 +/- 1.5 vs. ECC: 2.2 +/- 2.1 units [p = 0.05], frozen plasma: MPC: 1.2 +/- 1.8 vs. ECC: 1.9 +/- 2.4 units [p = 0.03]), postoperative bleeding (MPC: 521 +/- 283 vs. ECC: 615 +/- 326 ml/24 h, p = 0.09) were lower using MPC. ICU stay was shorter with MPC (1.6 +/- 1.6 days) compared to ECC (2.4 +/- 2.8 days, p = 0.001). One stroke occurred in each group. The ROCsafe MPC provides safe circulatory support for a wide range of aortic valve surgeries. Transfusion requirements, postoperative bleeding and length of ICU stay were markedly reduced compared to standard extracorporeal perfusion. Tajdini, Masih; Sardari, Akram; Forouzannia, Seyed Khalil; Baradaran, Abdolvahab; Hosseini, Seyed Mohammad Reza Interrupted aortic arch is a rare congenital abnormality with a high infancy mortality rate. The principal finding is loss of luminal continuity between the ascending and descending portions of the aorta. Because of the high mortality rate in infancy, interrupted aortic arch is very rare among adults. In this report, we describe the case of a 76-year-old woman with asymptomatic interrupted aortic arch, severe tricuspid regurgitation, and bicuspid aortic valve. To our knowledge, she is the oldest patient ever reported with this possibly unique combination of pathologic conditions. In addition to reporting her case, we review the relevant medical literature. PMID:27777532 Celiento, Michele; Scioti, Giovanni; Pratali, Stefano; Guarracino, Fabio; Bortolotti, Uberto The case is presented of an unusual complication after aortic valve replacement with a Freedom Solo bioprosthesis. Excision of the aortic valve created a discontinuity of the aortic annulus that was missed intraoperatively and left uncorrected after supra-annular placement of the bioprosthesis; this created a pseudoaneurysm with direct communication to the pericardial cavity. When implanting the Freedom Solo bioprosthesis, care must be taken to exclude the presence of any aortic annular discontinuity. Implantation of the Freedom Solo bioprosthesis is not precluded by this possible complication, provided that any annular disruption is promptly recognized and adequately closed before placement of the supra-annular sutures.	2	200	2	0	0	0	0.654968	2	139,213
The 10th release of the International Classification of Diseases (ICD-10) is the latest edition to the system of codes that classifies every disease or health problem around the world. The previous edition was released about four decades ago and hence this release was seen as a sweeping change in the medical coding world. ICD-10 provides a unique platform for practicing physicians and other healthcare professionals and has become the new standard for clinical data, claims processing, clinical documentation, and public health reporting. The benefits of ICD-10 transition begin with enhanced clinical documentation which enables physicians to analyze patient details, thereby lead to better care coordination and health outcomes. ICD-9 has approximately 13000 diagnosis codes which are in numeric form only ICD-10 has about 68000 alphanumeric diagnosis codes with 19 times as many procedure codes and 5 times as many diagnosis codes as ICD-9 Specific identification of diseases is not possible in ICD-9 ICD-10 codes allow you to identify etiology, anatomic site, severity as well as the first encounter with a disease ICD-9 does not allow specifying laterality or the region/part of the body affected Laterality is the new coding convention to increase specificity. Designated codes for conditions will require documentation for the side/region of the body ICD-9 was released almost 40 years back and has no provision to add new technologies or diagnoses ICD-10 has the provision to add new procedures as they are developed and new illnesses as they emerge ICD-9 used the old terminology for various diseases The ICD-10 terminology has been updated to reflect the current practices ICD-9 did not have the provision of combination codes ICD-10 has combination codes which makes it possible to code multiple diagnoses in one code Top 8 Advantages of ICD-10 Implementation Even though most healthcare providers have successfully transitioned towards ICD-10, there are still a few others who have either not implemented it properly, or are in the process of doing so. In case you are still not sure whether to make the transition or not, go through the following benefits of ICD-10 implementation to arrive at a conclusion - 1. Fair Pay: The new ICD-10 coding system is more granular in nature. This allows physicians to accurately report the complexity of the care provided and differentiate between chronic patients and those who come for routine check-ups. Under the ICD-9 system this distinction would have been lost. As a result, the customers can be charged as per the treatment provided, thereby leading to better transparency in payment procedures. 2. Greater Efficiency: By implementing ICD-10, a huge amount of data will be generated and can be mined for the betterment of public health. It allows governments and healthcare officials to track and respond to global health threats faster while comparing practices with the international community. Areas of injury research and trauma services evaluation have also witnessed a marked improvement in classifying the nature of injuries and correlating them with the proper cause, treatment, and outcome. 3. Lesser Fraud: Adoption of ICD-10 will result in fewer fraudulent and exaggerated claims, which increases the cost of medical care and health insurance premiums. The conversion to ICD-10 will eventually result in better patient care and more accurate reimbursement for providers as well. 4. Improved Healthcare Quality: With ICD-9, the main focus was on improving reimbursements. But the ICD-10 coding setup supports a performance-based payment system rather than aiming at returns. This will change the way healthcare functions currently and will improve the overall quality of care being provided. 5. Setting Health Policy: Since most of the world is using the ICD-10 code set, health officials can use the data to compare public health trends with global pandemics. This will help in setting-up better health policies across the world. 6. Performance Monitoring: The upgrade to ICD-10 will improve a provider's ability to monitor services and resource utilization, analyze healthcare costs, monitor outcomes, and measure performance. Greater detail on procedure types will allow providers to evaluate their own performance as compared to their peers, and take the necessary steps towards improvement. 7. Improved Quality in Clinical Documentation: The ICD-10 coding system is very much dependent on clinical documentation. Since thousands of diagnosis codes are added to ICD-10, the precision of the codes depend on clinical documents. So, with the implementation of ICD-10, quality of clinical documentation will improve. 8. Improving Relationships: An upgrade to ICD-10 helps healthcare providers improve their relations with providers and vendors as well. Providers can partner with payers for coding improvements. Both payers and providers can collaborate and help to improve the reimbursement processes, thereby improving their revenue stream and satisfaction. Dos and Don'ts of ICD-10 Implementation While ICD-10 is necessary to be implemented, healthcare providers should also ensure that it is executed properly, failing to which more problems might arise for the practitioners. Here are a few Do's and Don'ts of ICD-10 implementation - Conduct Training for the Coding Team: ICD-10 requires comprehensive training sessions for the medical coders. The training sessions must have case-based exercises which induce them to think logically and act independently when they start coding Choose the Right Technology: Many healthcare IT companies have launched several tools to aid the ICD-10 implementation process. It is important that one chooses the correct tool which suits their requirement Be Aware of the Latest ICD-10 Updates: Updates to ICD-10 are being made frequently and it is important that you stay updated with the latest changes happening in the industry to keep up with the ICD implementation Update Your Clients: Your clients must be regularly updated about the ICD-10 initiatives taken by you. Share your various plans, ideas, or even shortcomings which will show them your commitment towards ICD-10 Don't do it in a Hurry: Plan a proper ICD-10 implementation plan and work accordingly. The more it is delayed the riskier it is to work at the last minute. Let things happen as planned so that you get enough time to fix any problems arising during the implementation and integration process Don't Leave Everything to the Coders: The ICD coding system demands a lot of groundwork to be done before the actual implementation. The ICD transition must be a combined effort of the transition management team, IT team, and the medical billing team Leverage Our Knowledge of ICD-10 to Your Benefit Flatworld Solutions has been providing medical billing and coding services for over 11 years now. Our highly qualified team of medical billing specialists is adequately trained and well versed with the benefits of integrating ICD-10 codes. We provide high-quality services to clients around the world at very competitive prices. If you have any such requirement or would like to know about how Flatworld's ICD-10 knowledge can positively impact your practice, feel free to contact us or talk to one of our representatives and we will get back to you within 24 hours.	3	7	2	0	0	0	0.576745	2	1,469
Parkes Weber syndrome, PWS, Klippel-Trenaunay syndrome, KTS, Kasabach-Merritt syndrome, angioosteohypertrophy syndrome, cutaneous capillary malformation, congential vascular nevus, capillary hemangioma, port-wine stain, lymphedema KTW syndrome, Klippel-Trenaunay syndrome, angio-osteohypertrophy syndrome, naevus vasculosus osteohypertrophicus; Parkes-Weber syndrome is a similar entity involving the presence of an arteriovenous malformation with high-flow vessel malformations and characteristic skin capillary changes, with associated skeletal or soft tissue hypertrophy (also known as haemangiectatic hypertrophy). See also: Sturge-Weber syndrome First described by French physicians Klippel and Trenaunay in 1900, this syndrome is characterized by port-wine stain (capillary hemangioma), varicose veins and bony and soft tissue hypertrophy involving an extremity. Capillary hemangiomas (port-wine stain), stasis dermatitis, thrombophlebitis, cellulitis, limb disparity, and more serious sequelae such as thrombosis, coagulopathy, bleeding, pulmonary embolism, and congestive heart failure. (1), lymphedema is also a consistent complication. Other indications may include asymmetric face, facial haemangiomas, advanced tooth eruption, macrocephaly, heterotopia, glaucoma, cutaneous pustules/ulcers Klippel Trenaunay appears to be a non-hereditary syndrome although there is still an ongoing discussion involving this. Simple diagnosis can be made by observation and examination. Venous and lymphatic complications are diagnosed using radiological tests such as lymphoscintigraphy, ultra-sounds, and MRI. Venograms, and arteriograms may also be used. Treatment is varied for the different symptoms present. Compression garments are used to control the lymphedema, prophylactic antibiotics are of course, used to treat the cellulitis and lymphangitis spells. Orthopedic procedures are available for the limb hypertrophy and wound treatment is sometimes necessary for ulcerations. Other treatments for the symptoms or complications include lasers for the hemangiomas, and surgical intervention for the vascular anomalies may be called for. This syndrome is characterised by the presence of the following triad: The affected limb may also have abnormalities of lymphatic channels and drainage along with arterial malformations. Rarely, the condition can affect more than one limb, an internal organ or the head and neck. Blood flow through the capillary abnormalities in KTW syndrome is low velocity, in contrast to Parkes-Weber syndrome where there is a true arteriovenous malformation with high velocity blood flow. This is unknown, though several theories exist. Damage or malformation of the sympathetic ganglia in-utero, damage to deep veins leading to venous hypertension, or mesodermal maldevelopment causing the formation of microscopic arteriovenous communications have all been suggested.1 The condition appears to be sporadic but there are families in whom the condition may be inherited in an autosomal dominant fashion with marked variation in penetrance. An abnormality in a gene locus on the long arm of chromosome 5 appears to be involved.2 This is a rare sporadic condition and there are no available figures for its annual incidence or prevalence in the population. The characteristic capillary haemangioma will be visible from birth in the vast majority of cases (98% in one series).2 The skin lesion has a characteristic 'port-wine stain' appearance, being deep-purple in colour (in contrast to that of Parkes-Weber syndrome which appears bright red), with clear demarcation from normal skin. Varicosities and limb hypertrophy are not always present at birth and may take several years to manifest. Abnormal veins and marked varicosities may be present. Limb hypertrophy may begin by affecting the digits only and cause macrodactyly, syndactyly, polydactyly or oligodactyly. An increase in limb girth may be the only feature where soft tissues rather than bones are predominantly affected. Limb-lengthening may present initially as gait disturbance. If the head is affected then the syndrome may cause macrocephaly and/or mental retardation. Lymphedema may complicate the condition and contribute to the limb enlargement. Rarely, the affected limb may show atrophy rather than hypertrophy. Thrombophlebitis is a common consequence in patients with large venous varicosities. If the cutaneous haemangioma is large it may cause a consumptive coagulopathy known as Kasabach-Merritt syndrome typified by anaemia, thrombocytopenia, prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), reduced fibrinogen levels, and elevation of fibrin degradation products. Pulmonary or venous thromboembolism may occur rarely as part of the Kasabach-Merritt syndrome. Other features include:1 Imaging of the deep venous systems may be carried out, most often using magnetic resonance imaging in a modern setting. Arteriography or duplex ultrasound scanning may be used to investigate the possibility of an arteriovenous malformation. CT scanning may be used to determine exact limb-length discrepancy as a prelude to any corrective surgery. Lymphoscintigraphy may be used to assess the lymphatic system and the cause of limb-length discrepancy.3 There is no curative therapy and management aims to ameliorate the patient's symptoms and correct the consequences of limb-length discrepancy. Graduated compression garments help to reduce the effect of chronic venous insufficiency in the affected limb. Intermittent pneumatic compression pumps may also be used to the same effect. Cellulitis and thrombophlebitis can be managed with antibiotics, limb elevation, analgesia and corticosteroids. Prophylactic aspirin ± anticoagulants may be used in those who have recurrent thrombophlebitis, or before surgery/during pregnancy. Women who have the syndrome should avoid the use of hormonal contraceptive methods, due to the increased risk of venous thrombosis. Pregnant women with KTW syndrome need careful monitoring due to a range of haematological, obstetric and anaesthetic complications.4 Limb-length discrepancy may be treated with orthoses or orthopaedic surgery, depending on its severity. Laser therapy can be used to lessen the cosmetic effect of the cutaneous stain. Surgery may be used to treat severe venous malformations but remains controversial as long-term outcomes appear to be altered little by such intervention. Endovenous laser therapy of the greater saphenous vein appears to help some cases of lower limb varicosity. De-bulking surgery for grossly enlarged limbs is occasionally used but carries a significant risk of lymphatic and venous damage. Amputation may be used in cases where the limb is of little functional use and causes severe complications. Life expectancy is largely normal, depending on the severity of the malformation and thus the likelihood of complications. About 10% of patients are affected by pulmonary embolism.3 There may be significant morbidity associated with the condition but most patients do well with conservative therapy and lead relatively normal lives. Amputation is rarely needed. 1.Lisko J and Fish F, Klippel-Trenaunay-Weber Syndrome, eMedicine (2006). Good overview from dermatology viewpoint. 2.OMIM - Klippel-Trenaunay-Weber Syndrome, 2006 (Genetic detail). 3.Tonsgard J, Klippel-Tranaunay-Weber Syndrome, eMedicine (2006).; Overview from paediatrics viewpoint. 4.Sivaprakasam MJ, Dolak JA; Anesthetic and obstetric considerations in a parturient with Klippel-Trenaunay syndrome. Can J Anaesth. 2006 May;53(5):487-91. [abstract] 5.Agrawal V, Minhas S, Ralph DJ; Venogenic erectile dysfunction in Klippel-Trenaunay syndrome. BJU Int. 2006 Feb;97(2):327-8. [abstract] Alternative titles; symbols KTW SYNDROME KLIPPEL-TRENAUNAY SYNDROME; KTS ANGIOOSTEOHYPERTROPHY SYNDROMEGene map locus 5q13.3 A number sign (#) is used with this entry because at least some cases of Klippel-Trenaunay syndrome are caused by mutation in or gain-of-function translocation involving the VG5Q gene (608464). The features of Klippel-Trenaunay-Weber syndrome are large cutaneous hemangiomata with hypertrophy of the related bones and soft tissues. The disorder resembles, clinically and in its lack of definite genetic basis, Sturge-Weber syndrome (185300), and indeed the 2 have been associated in some cases (Harper, 1971). Suggestions of a genetic 'cause' are meager (Waardenburg, 1963). See 116860. Lindenauer (1965) described brother and sister. He suggested that when arteriovenous fistula is also present, the disorder is distinct from the KTW syndrome and might be called Parkes Weber syndrome, since Weber (1907) described cases of this type as well as cases seemingly identical to those of Klippel and Trenaunay (1900). Lindenauer (1965) also suggested that the deep venous system is atretic in KTW syndrome and, as a corollary, that stripping of varicose veins is unwise. Campistol et al. (1988) described an affected 19-year-old woman who had multiple renal pelvic hemangiomas and renal artery aneurysm. Viljoen (1988) reviewed the clinical features of the syndrome. Lawlor and Charles-Holmes (1988) described a 25-year-old woman with KTW syndrome who had life-threatening menorrhagia due to uterine hemangioma. In an infant with this syndrome, Mor et al. (1988) observed hydrops fetalis (gross edema of the limbs, ascites, and palpable liver). The infant lost 520 gm of weight in the first 6 days of life without medication. Aelvoet et al. (1992) provided evidence that Klippel-Trenaunay syndrome occasionally shows familial aggregation. In addition, they found isolated vascular nevi to be overrepresented in relatives of KTS patients. Happle (1993) suggested that what he referred to as paradominant inheritance most satisfactorily explains the findings. According to this concept, KTS would be caused by a single gene defect. Heterozygous individuals would be, as a rule, phenotypically normal, and therefore the allele would be transmitted imperceptibly through many generations. The trait would only be expressed when a somatic mutation occurred in the normal allele at an early stage of embryogenesis, giving rise to a clonal population of cells either homozygous or hemizygous for the KTS mutation. One example of a genetic mechanism that might cause homozygosity of a cell population arranged in a mosaic pattern is somatic recombination. Presumably, diffuse involvement of the entire body would not be possible because of nonviability of embryos developing from a homozygous zygote. Muluk et al. (1995) described the case of a 32-year-old man in whom progressive pulmonary insufficiency was found to be due to repeated pulmonary emboli from the deep venous malformations associated with KTS. Samuel and Spitz (1995) reviewed the clinical features and management of 47 children with KTS treated since 1970. Hemangiomas and soft tissue and/or skeletal hypertrophy were present in all 47 patients; venous varicosities developed in 37 (79%). None had clinical evidence of macrofistulous arteriovenous communications. Thromboembolic episodes occurred in 5 children (11%), and 25 (53%) experienced thrombophlebitis. The Kasabach-Merritt syndrome (141000) was observed in 21 (45%), and 6 (13%) presented with high-output heart failure. Other manifestations included hematuria in 5 (11%), rectal or colonic hemorrhage in 6 (13%), and vaginal, vulval, or penile bleeding in 6 (13%) children with visceral and pelvic hemangiomas. In 26 patients (55%), symptomatic treatment only was required. Surgery was undertaken in selected cases for complications of the hemangioma, for cosmetic reasons, and for chronic venous insufficiency. Only 1 of the 4 children who underwent resection of varicose veins improved. Whelan et al. (1995) reported the case of a girl with KTW syndrome associated with a reciprocal translocation: t(5;11)(q13.3;p15.1). This raised the possibility that this disorder is due to a single gene defect and that the gene is located on 5q or p11. At birth a capillary hemangioma of the right arm and a vascular anomaly of the left trunk with extension onto the left thigh was noted. At age 3 months, the patient's mother noted that the right second toe was larger than corresponding left toe. Subsequent progression to right leg hypertrophy was noted in the first 5 years of life. Ceballos-Quintal et al. (1996) reported a family in which a child had large skin hemangiomata, overgrowth of the right leg, and severe heart defects (patent ductus arteriosus (see 607411), atrial septal defect, prolapsed tricuspid valve, and pulmonic stenosis). Her mother had a large capillary hemangioma on the left side of the back and developed severe varicosities in both legs. The maternal grandmother developed severe varicosities of the legs at a young age. The clinical signs in the mother and maternal grandmother were interpreted as mild expression of the KTW syndrome and the family tree was thought to support autosomal dominant inheritance. By ultrasound examination, Christenson et al. (1997) made the prenatal diagnosis of KTW syndrome complicated by early fetal congestive heart failure. The postnatal course was complicated by Kasabach-Merritt syndrome of thrombocytopenia due to platelet consumption within the hemangioma. Neonatal cardiopulmonary resuscitation and limb amputation were required. Berry et al. (1998) reviewed 49 cases of KTS. All were sporadic. They speculated that the disorder may be due to a somatic mutation for a factor critical to vasculogenesis and angiogenesis in embryonic development. Lorda-Sanchez et al. (1998) presented an epidemiologic analysis of a consecutive series of cases of KTW syndrome identified in the Spanish Collaborative Study of Congenital Malformations. They found an increase in parental age and in the number of pregnancies, as well as familial occurrence of hemangiomas. These observations suggested a genetic contribution to the occurrence of KTW syndrome. Although the effect of increased paternal age on the origin of spontaneous germline mutations is well documented for dominant conditions, sporadic conditions that are presumably caused by somatic mosaicism are not supposed to show advanced parental age. The increased parental age would be consistent with the model of paradominant inheritance. Epidemiologic studies of retinoblastoma, a classic example of the 2-hit model of Knudson, have shown an association of older parental age with the first mutation event in germinal cells in sporadic hereditary retinoblastoma (DerKinderen et al., 1990) but no evidence for risk factors related to the second somatic mutation (Matsunaga et al., 1990). Sperandeo et al. (2000) described a family in which 1 first cousin had KTW syndrome and the other had Beckwith-Wiedemann syndrome (BWS; 130650). The probands, sons of 2 sisters, showed relaxation of the maternal IGF2 (147470) imprinting, although they inherited different 11p15.5 alleles from their mothers and did not show any chromosome rearrangement. The patient with BWS also displayed hypomethylation of KvDMR1, a maternally methylated CpG island within an intron of the KvLQT1 gene (607542). The unaffected brother of the BWS proband shared the same maternal and paternal 11p15.5 haplotype with his brother, but the KvDMR1 locus was normally methylated. Methylation of the H19 gene (103280) was normal in both the BWS and KTW syndrome probands. Linkage between the IGF2 receptor gene (IGF2R; 147280) and the tissue overgrowth was excluded. These results raised the possibility that a defective modifier or regulatory gene unlinked to 11p15.5 caused a spectrum of epigenetic alterations in the germline or early development of both cousins, ranging from the relaxation of IGF2 imprinting in the KTW syndrome proband to disruption of both the imprinted expression of IGF2 and the imprinted methylation of KvDMR1 in the BWS proband. The data indicated that loss of IGF2 imprinting is not necessarily linked to alteration of methylation at the KvDMR1 or H19 loci and supports the notion that IGF2 overexpression is involved in the etiology of tissue hypertrophy observed in different overgrowth disorders, including KTW syndrome. Cohen (2000) defined Klippel-Trenaunay syndrome and challenged 4 conceptions frequently found in the literature on this disorder. He considered it improper to add arteriovenous fistulas to the syndrome and on that basis to rename the disorder Klippel-Trenaunay-Weber syndrome. Although Parkes Weber syndrome (as Cohen called it) and Klippel-Trenaunay syndrome are similar, slow flow venous malformations are predominant in KTS, whereas arteriovenous fistulas are always found in Parkes Weber syndrome. Large series of patients with Parkes Weber syndrome were reported by Robertson (1956) and Young (1988). The involved limb is warm. The color of the cutaneous vascular malformation is usually more diffuse and pinker than that observed in KTS. Lymphatic malformations found in KTS do not occur in Parkes Weber syndrome. Cohen (2000) questioned that Sturge-Weber syndrome and KTS are the same disorder. Cohen (2000) considered the affected brother and sister described by Lindenauer (1965) as the only well-documented examples of KTS in a family. The de novo translocation t(8;14)(q22.3;q13), reported by Timur et al. (2000) and Wang et al. (2001), points to a pair of chromosomes different from those focused on by Whelan et al. (1995) as the possible site of the Klippel-Trenaunay gene. Wang et al. (2001) used FISH to define the breakpoints on 8q22.3 and 14q13 in relation to specific markers and suggested that their study provided the basis for the fine mapping and ultimate cloning of a novel vascular gene at 8q22.3 or 14q13. Tian et al. (2004) characterized the breakpoint of the translocation in a patient with Klippel-Trenaunay syndrome described by Whelan et al. (1995) and identified the VG5Q gene (608464). The chromosomal translocation results in increased expression of VG5Q in the translocation patient. They also identified 5 of 130 patients with Klippel-Trenaunay syndrome who were heterozygous for an E133K mutation (608464.0001), which also results in a gain of function. Tian et al. (2004) suggested that patients with the VG5Q E133K mutation may carry a second mutational hit in VG5Q or another gene within the affected tissues. Timur et al. (2004) identified a de novo supernumerary ring chromosome in a patient with mild mental retardation, long tapering fingers, elongated and thin feet, and KTS. The ring marker chromosome was found to be mosaic, present in 24% of cells, and was shown to be derived from chromosome 18, r(18). FISH was used to define the breakpoints involved in formation of the r(18). The 18p breakpoint was located less than 10 cM from the centromere; the 18q breakpoint was located between the centromere and BAC clone 666n19 (GenBank AC036178), representing a region of less than 40 kb. The data suggested that the r(18) mostly originated from 18p, with an estimated size of less than 10 cM. Brooksaler (1966); Furukawa et al. (1970); Koch (1956); Servelle (1985); Viljoen et al. (1987) 1. Aelvoet, G. E.; Jorens, P. G.; Roelen, L. M. : Genetic aspects of the Klippel-Trenaunay syndrome. Brit. J. Derm. 126: 603-607, 1992. PubMed ID : 1319193 2. Berry, S. A.; Peterson, C.; Mize, W.; Bloom, K.; Zachary, C.; Blasco, P.; Hunter, D. : Klippel-Trenaunay syndrome. Am. J. Med. Genet. 79: 319-326, 1998. PubMed ID : 9781914 3. Brooksaler, F. : The angioosteohypertrophy syndrome (Klippel-Trenaunay-Weber syndrome). Am. J. Dis. Child. 112: 161-164, 1966. PubMed ID : 5943999 4. Campistol, J. M.; Agusti, C.; Torras, A.; Campo, E.; Abad, C.; Revert, L. : Renal hemangioma and renal artery aneurysm in the Klippel-Trenaunay syndrome. J. Urol. 140: 134-136, 1988. PubMed ID : 2837586 5. Ceballos-Quintal, J. M.; Pinto-Escalante, D.; Castillo-Zapata, I. : A new case of Klippel-Trenaunay-Weber (KTW) syndrome: evidence of autosomal dominant inheritance. Am. J. Med. Genet. 63: 426-427, 1996. PubMed ID : 8737646 6. Christenson, L.; Yankowitz, J.; Robinson, R. : Prenatal diagnosis of Klippel-Trenaunay-Weber syndrome as a cause for in utero heart failure and severe postnatal sequelae. Prenatal Diag. 17: 1176-1180, 1997. PubMed ID : 9467816 7. Cohen, M. M., Jr. : Klippel-Trenaunay syndrome. (Editorial) Am. J. Med. Genet. 93: 171-175, 2000. PubMed ID : 10925375 8. DerKinderen, D. J.; Koten, J. W.; Tan, K. E. W. P.; Beemer, F. A.; Van Romunde, L. K. J.; Den Otter, W. : Parental age in sporadic hereditary retinoblastoma. Am. J. Ophthal. 110: 605-609, 1990. PubMed ID : 2248323 9. Furukawa, T.; Igata, A.; Toyokura, Y.; Ikeda, S. : Sturge-Weber and Klippel-Trenaunay syndrome with nevus of Ota and Ito. Arch. Derm. 102: 640-645, 1970. PubMed ID : 5501905 10. Happle, R. : Klippel-Trenaunay syndrome: is it a paradominant trait? (Letter) Brit. J. Derm. 128: 465 only, 1993. PubMed ID : 8388238 11. Harper, P. S. : Sturge-Weber syndrome with Klippel-Trenaunay-Weber syndrome. Birth Defects Orig. Art. Ser. VII(8): 314-317, 1971. 12. Klippel, M.; Trenaunay, P. : Du naevus variqueux osteo-hypertrophique. Arch. Gen. Med. 185: 641-672, 1900. 13. Koch, G. : Zur Klinik, Symptomatologie, Pathogenese und Erbpathologie des Klippel-Trenaunay-Weberschen syndroms. Acta Genet. Med. Gemellol. 5: 326-370, 1956. 14. Lawlor, F.; Charles-Holmes, S. : Uterine haemangioma in Klippel-Trenaunay-Weber syndrome. J. Roy. Soc. Med. 81: 665-666, 1988. 15. Lindenauer, S. M. : The Klippel-Trenaunay syndrome: varicosity, hypertrophy and hemangioma with no arteriovenous fistula. Ann. Surg. 162: 303-314, 1965. PubMed ID : 14327016 16. Lindenauer, S. M. : The Klippel-Trenaunay-Weber syndrome: varicosity, hypertrophy and hemangioma with no arteriovenous fistula. Ann. Surg. 162: 303-314, 1965. PubMed ID : 14327016 17. Lorda-Sanchez, I.; Prieto, L.; Rodriguez-Pinilla, E.; Martinez-Frias, M. L. : Increased parental age and number of pregnancies in Klippel-Trenaunay-Weber syndrome. Ann. Hum. Genet. 62: 235-239, 1998. PubMed ID : 9803268 18. Matsunaga, E.; Minoda, K.; Sasaki, M. S. : Parental age and seasonal variation in the births of children with sporadic retinoblastoma: a mutation-epidemiologic study. Hum. Genet. 84: 155-158, 1990. PubMed ID : 2298450 19. Mor, Z.; Schreyer, P.; Wainraub, Z.; Hayman, E.; Caspi, E. : Nonimmune hydrops fetalis associated with angioosteohypertrophy (Klippel-Trenaunay) syndrome. Am. J. Obstet. Gynec. 159: 1185-1186, 1988. PubMed ID : 2847530 20. Muluk, S. C.; Ginns, L. C.; Semigran, M. J.; Kaufman, J. A.; Gertler, J. P. : Klippel-Trenaunay syndrome with multiple pulmonary emboli: an unusual cause of progressive pulmonary dysfunction. J. Vasc. Surg. 21: 686-690, 1995. PubMed ID : 7707572 21. Robertson, D. J. : Congenital arteriovenous fistulae of the extremities. Ann. Roy. Coll. Surg. Eng. 18: 73-98, 1956. PubMed ID : 13292864 22. Samuel, M.; Spitz, L. : Klippel-Trenaunay syndrome: clinical features, complications and management in children. Brit. J. Surg. 82: 757-761, 1995. PubMed ID : 7542989 23. Servelle, M. : Klippel and Trenaunay's syndrome: 768 operated cases. Ann. Surg. 201: 365-373, 1985. PubMed ID : 2983626 24. Sperandeo, M. P.; Ungaro, P.; Vernucci, M.; Pedone, P. V.; Cerrato, F.; Perone, L.; Casola, S.; Cubellis, M. V.; Bruni, C. B.; Andria, G.; Sebastio, G.; Riccio, A. : Relaxation of insulin-like growth factor 2 imprinting and discordant methylation at KvDMR1 in two first cousins affected by Beckwith-Wiedemann and Klippel-Trenaunay-Weber syndromes. Am. J. Hum. Genet. 66: 841-847, 2000. PubMed ID : 10712200 25. Tian, X.-L.; Kadaba, R.; You, S.-A.; Liu, M.; Timur, A. A.; Yang, L.; Chen, Q.; Szafranski, P.; Rao, S.; Wu, L.; Housman, D. E.; DiCorleto, P. E.; Driscoll, D. J.; Borrow, J.; Wang, Q. : Identification of an angiogenic factor that when mutated causes susceptibility to Klippel-Trenaunay syndrome. Nature 427: 640-645, 2004. PubMed ID : 14961121 26. Timur, A. A.; Driscoll, D. J.; Wang, Q. : A de novo translocation, t(8;14)(q22.3;q13), associated with Klippel-Trenaunay syndrome (KTS). (Abstract) Am. J. Hum. Genet. 67 (Suppl. 2): A2115, 2000. 27. Timur, A. A.; Sadgephour, A.; Graf, M.; Schwartz, S.; Libby, E. D.; Driscoll, D. J.; Wang, Q. : Identification and molecular characterization of a de novo supernumerary ring chromosome 18 in a patient with Klippel-Trenaunay syndrome. Ann. Hum. Genet. 68: 353-361, 2004. PubMed ID : 15225160 28. Viljoen, D.; Saxe, N.; Pearn, J.; Beighton, P. : The cutaneous manifestations of the Klippel-Trenaunay-Weber syndrome. Clin. Exp. Derm. 12: 12-17, 1987. PubMed ID : 2820629 29. Viljoen, D. L. : Klippel-Trenaunay-Weber syndrome (angio-osteohypertrophy syndrome). J. Med. Genet. 25: 250-252, 1988. PubMed ID : 2835482 30. Waardenburg, P. J. : Hypertrophic haemangiectasia (Klippel-Trenaunay-Weber's syndrome).In: Genetics and Ophthalmology. Vol. 2. : :Springfield, Ill.: Charles C Thomas (pub.) 1963. Pp. 1381-1386. 31. Wang, Q.; Timur, A. A.; Szafranski, P.; Sadgephour, A.; Jurecic, V.; Cowell, J.; Baldini, A.; Driscoll, D. J. : Identification and molecular characterization of de novo translocation t(8;14)(q22.3;q13) associated with a vascular and tissue overgrowth syndrome. Cytogenet. Cell Genet. 95: 183-188, 2001. PubMed ID : 12063397 32. Weber, F. P. : Angioma formation in connection with hypertrophy of limbs and hemihypertrophy. Brit. J. Derm. 19: 231-235, 1907. 33. Whelan, A. J.; Watson, M. S.; Porter, F. D.; Steiner, R. D. : Klippel-Trenaunay-Weber syndrome associated with a 5:11 balanced translocation. Am. J. Med. Genet. 59: 492-494, 1995. PubMed ID : 8585570 34. Young, A. E. : Combined vascular malformations.In: Mulliken, J. B.; Young, A. E. (eds.) : Vascular Birthmarks. Hemangiomas and Malformations. Philadelphia: W.B. Saunders 1988. Pp. 246-274. EDIT HISTORY 01/08/2007 [Article in Japanese] Tokuda A, Kamioka E, Sasaki A, Nakamura S, Tabeta H. Department of Respiratory Internal Medicine, Funabashi Municipal Medical Center. Abstract Klippel-Trenaunay-Weber syndrome (KTWS) is a rare congenital disorder characterized by varicose veins, cutaneous hemangiomas, hypertrophy of soft tissue and bone and arteriovenous malformations. We present a case of a 43-year-old man with KTWS. He experienced progressive pulmonary hypertension due to recurrent pulmonary embolism, which developed despite adequate anticoagulation. This case report suggests that patients with KTWS need more aggressive management and treatment of their thromboembolitic state and pulmonary hypertension. Takata M, Watanabe K, Matsubara H, Takato K, Nomura I, Tsuchiya H. Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, Japan. Key words: external fixators; Ilizarov technique; KlippelTrenaunay-Weber syndrome; leg length inequalit Abstract We report a case of Klippel-Trenaunay-Weber syndrome in a 31-year-old woman who presented with hypertrophy of the left leg. She had severe osteoarthritic changes in the left hip joint secondary to the lack of acetabular coverage of the femoral head as the result of lateral inclination of the pelvis owing to leg-length discrepancy of 4 cm. The centre-edge angle (coverage ratio of the acetabulum to the femoral head) was improved from 15º to 33º after a foot lift. She underwent osteotomy and lengthening of the normal contralateral tibia using a Taylor spatial frame. Hip arthroplasty could be avoided as osteoarthritic changes of the hip joint had improved. Plaza-Martínez Á, Ortiz-Monzón E, Gómez-Palonés FJ, Genovés-Gascó B, Martínez-Perelló I, Martínez-Parreño C. Angiology, Vascular and Endovascular Surgery Department, Hospital Universitario Doctor Peset, Valencia, Spain. [email protected] BACKGROUND: The association of Klippel-Trénaunay-Weber syndrome (KTWS) with artery aneurysms is very rare. METHODS AND RESULTS: A 61-year-old man, diagnosed with left lower limb KTWS, presented with a venous ulcer and a popliteal aneurysm measuring 3.5 cm in diameter in the same limb. Endovascular treatment with covered stent was applied with good morphological and clinical results. We report a singular case of the association of a popliteal aneurysm with KTWS and its endovascular treatment. This treatment enabled exclusion of the popliteal artery aneurysm with safety and effectiveness and reduced the number of arteriovenous fistulas. Source Children's Medical Center of Dallas, Dallas, Texas 75235, USA. [email protected] Klippel-Trénaunay-Weber Syndrome (KTWS) is characterized by a combination of vascular malformations of the skin, abnormalities of the venous and lymphatic systems, and limb enlargement due to bone and soft tissue hypertrophy. The precise etiology is unknown. There is typically no evidence of arteriovenous shunting. Venous malformations are present at birth, are known to progress as the patient grows, and do not regress. Blood flow through these malformations is sluggish, causing ischemia and thrombotic painful events. Nerve blocks are often used to treat pain that is unrelieved by other pharmacologic and nonpharmacologic measures. In this particular case, a stellate ganglion nerve block was the treatment of choice. The stellate ganglion is part of the sympathetic nervous system made up of the inferior cervical and first thoracic ganglia. The nerve block was performed under fluoroscopy by an anesthesiologist board certified in pediatric pain management. The goal of the block was to relieve the patient's pain by calming painful nerve impulses produced by the stellate ganglion and improving blood flow to the area by vasodilating the vessels distal to the site of the block. The goal of this report was to impress upon health care professionals the effectiveness of nerve blocks in improving and sometimes eliminating a patient's pain, as well as the importance of exhausting all options to alleviate/improve pain in our patients. To protect the privacy of this patient and family, the details of the actual case were revised. Full Length Article: Pain Management Nursing In 1940, Kasabach and Merritt described a male infant with a discolored, indurated lesion on his left thigh that grew rapidly and affected the entire left leg, scrotum, abdomen, and thorax. The infant also had consumptive coagulopathy andthrombocytopenia. This association has become known as Kasabach-Merritt syndrome (KMS) and more recently as the Kasabach-Merritt phenomenon (KMP). For an overview see: Keywords: Klippel–Trenaunay syndrome, phakomatosis, Sturge–Weber syndrome Synonyms and related keywords: Parkes Weber syndrome, Klippel-Trenaunay syndrome, KTWS, port-wine stain, varicose veins, bony and soft tissue hypertrophy, arteriovenous malformation Ming H Jih MD PhD Dermatology Online Journal 9(4): 31 From the Ronald O. Perelman Department of Dermatology, New York University ICD-9 - Klippel-Trenaunay syndrome 759.89 ICD-10 - Q87.2 Congenital malformation syndromes predominantly involving limbs Syndrome: · Holt-Oram · Klippel-Trénaunay-Weber · nail patella · Rubinstein-Taybi · sirenomelia · thrombocytopenia with absent radius [TAR] · VATER EUROCAT – Q87.21 EUROCAT is the “European network of population based registries for congenital anomalies” They were founded in 1979, with the goal of improving the collection of data about congenital disorders, and the standardization of that data.	2	21	1	0	1	4	0.872741	6	8,412
Health services framework and competent authoritiesHealthcare bodies Describe the bodies and their responsibilities (public and private sector) concerned with the delivery of healthcare and appropriate products for treatment. The responsibility for healthcare in Sweden is divided between the government, the Swedish county councils and local municipalities. On a governmental level, the Ministry of Health and Social Affairs is responsible for all policies related to social welfare in Sweden, including policies regarding the delivery of healthcare. The Ministry of Health and Social Affairs works in concert with various national government agencies, such as the National Board of Health and Welfare, which is responsible for all social services, health and medical services, patient safety and epidemiology, and the Health and Social Care Inspectorate, which is responsible for supervising healthcare and social care, as well as healthcare care staff. On a regional level, the Swedish county councils are responsible for the financing and delivering of healthcare services to citizens. The healthcare is then, by agreement with the county councils, provided by private and public healthcare providers. Care of elderly and disabled persons is, however, provided locally by the Swedish municipalities. When it comes to appropriate products for treatment, the Medical Products Agency (MPA) is responsible for regulation and surveillance of the development, manufacturing and sale of medicinal drugs, medical devices and cosmetics. The Social Care Inspectorate is responsible for the supervision of self-made medical devices as well as the way in which medical devices and medicinal products are prescribed, put into use, used and handled.Competent authorities for authorisation Identify the competent authorities for approval of the marketing of medicinal products and medical devices. What rules apply to deciding whether a product falls into either category or other regulated categories? The MPA is the competent authority for approval of the marketing of new medicinal products and market entry for medical devices in Sweden. The main regulatory frameworks for medicinal products are the Medicinal Products Act (2015:315) and the Medicinal Products Ordinance (2015:458), which are based on EU Directives 2001/83/EC and 2001/82/EC (the Medicinal Products Directives). The definition of ‘medicinal product’ corresponds with the definition in the Medicinal Products Directives. For more details regarding the framework for medicinal products, see the EU chapter. The main regulatory frameworks for medical devices are the Medical Devices Act (1993:584) and Medical Devices Ordinance (1993:876), which are based on EU Directives 90/385/EEC, 93/42/EEC and 98/79/EC (the Medical Device Directives). For more details regarding the framework for medical devices in the Medical Device Directives, and the new EU Regulations 2017/745 and 2017/746 coming into force in May 2020, see the EU chapter. In short, the intended use and the mechanisms of action of the device control whether a device constitutes a medical device or not. The difference between a medicinal product and medical device is that, whereas the mode of action of a medicinal product is pharmacological, immunological or metabolic, medical devices work by other means; for example, by a physical or mechanical mode of action. As for cosmetics, EU Regulation (EC) No. 1223/2009 on cosmetic products is implemented in Swedish law by the Ordinance on cosmetic products (2013:413). The Regulation (and the Ordinance) defines cosmetic products as any substance or mixture intended to be placed in contact with the external parts of the human body exclusively or mainly to clean it, perfume it, change its appearance, protect it, keep it in good condition or to correct body odours. The main distinction between medicinal products and cosmetic products is thus that cosmetic products are applied externally without any intended internal effects; if a product is applied externally but has an intended internal effect it is no longer a cosmetic product. All cosmetic products must comply with the Swedish Environmental Code (1998:808) and the Swedish Environmental Inspection Regulation (2011:13). Food supplements are regulated by food laws and regulations in Sweden. However, if the purpose of a food supplement is to prevent or treat disease, or to adjust or modify physiological functions by pharmacological, immunological or metabolic mode of action (ie, in accordance with the definition of ‘medicinal product’ mentioned above), it shall be classified as a medicinal product.Approval framework Describe the general legislative and regulatory framework for approval of marketing of medicinal products and medical devices. All medicinal products in Sweden must be approved by the MPA, sometimes in concert with other medicinal products agencies in other EU member states, or the EU Commission. The requirements for the approval of new medicinal products included in the Medicinal Products Act are based on and correspond with the requirements set forth in the Medicinal Products Directives. For more details regarding the requirements for approval of new medicinal products in the Medicinal Products Directives, see the EU chapter. All medicinal products need to be of good quality and be appropriate as well as effective in order to obtain a marketing authorisation. The application procedure for clearance by the MPA is included in MPA Regulation LVFS 2011:19. Medical devices do not need approval by the MPA. Instead, market access is conditional upon CE marking. According to MPA Regulation LVFS 2003:11, some medical devices must, however, be registered by the MPA; for example, in vitro diagnostic products and some categories of medical devices as set out in the Regulation. This registration does not mean, however, that the MPA has approved the medical device. All medical devices must, however, comply with the requirements in the Medical Devices Act, which is based on and corresponds with the Medical Device Directives. For more details regarding the requirements for medical devices, see the EU chapter. A medical device needs to be safe and fit for its designated purpose. A medical device that meets the requirements shall be provided with a CE marking. All labelling and instructions for use of medical devices must be written in Swedish according to MPA Regulations LVFS 2001:5, LVFS 2003:11 and LVFS 2001:7. As for medicinal products, there are detailed provisions regarding labelling in LVFS 2005:11, which prescribes that the labelling on the outer package and the container shall be in Swedish. Clinical practiceApplicable rules What legislation controls and which rules apply to ethics committee approval and performance of clinical trials in your territory for medicinal products and medical devices? Primarily, the Medicinal Products Act, the Medicinal Products Ordinance, the Ethical Review Act (2003:460) and MPA Regulation LVFS 2011:19 on clinical trials, which refers to Directives 2001/20/EC and 2005/28/EC regarding good clinical practice, apply to ethics committee approval and performance of clinical trials. The Swedish Association of the Pharmaceutical Industry (LIF) has also issued a framework for ethical rules for the pharmaceutical industry in Sweden (the LER Rules), which contain specific rules on conducting clinical trials. All clinical trials of medicinal products must follow the European Medicines Agency (EMA) Guideline on Strategies to Identify and Mitigate Risks for First-in-Human Clinical Trials with Investigational Medicinal Products. Applications are filed with the Swedish Ethical Review Authority. New EU Regulation No. 536/2014 on clinical trials, replacing EU Directive 2001/20/EC, entered into force on 16 June 2014. However, its application is awaiting the development of a fully functional EU clinical trials portal and database. For the purpose of implementing the new Regulation, the Swedish government has prepared the Additional Provisions on Ethical Review for the EU Regulation on Clinical Trials Act 2018:1091, which is ready to come into force. As for medical devices, clinical trials for the purpose of creating documentation for CE marking are primarily regulated by the Medical Devices Act, the Medical Devices Ordinance, MPA Regulations LVFS 2003:11 on active implants and LVFS 2001:5 on medical devices. All clinical trials for medical devices should be in line with the Swedish standards SS-EN 12155:2011 (for clinical trials) and SS-EN ISO 14971:2012 (for risk management). Furthermore, all clinical trials for medicinal products and medical devices must be conducted in accordance with the latest version of the World Medical Association’s Declaration of Helsinki and be registered with the European Clinical Trials Register.Reporting requirements What requirements exist for reporting the commencement of a trial and its results to the competent authorities or the public? Clinical trials for medicinal products and medical devices require prior approval from both the MPA and an ethics committee (the Swedish Ethical Review Authority). For medicinal products, the reporting of the commencement of a trial to the MPA shall be made through an application document accompanied with a clinical investigation plan and other required information in accordance with the Medicinal Products Act and MPA Regulation LVFS 2011:9. For medical devices, the reporting of the commencement of a trial to the MPA shall be made through an application document accompanied with a clinical investigation plan and other required information in accordance with the Medical Devices Act and MPA Regulations LVFS 2003:11 on medical devices and LVFS 2001:5 on active implants. The results of clinical trials for medicinal products shall be reported to the European Clinical Trials Database (EudraCT); for more information, see the EU chapter. The results of clinical trials of medical devices shall be concluded in a complete report to be provided to the MPA upon request.Consent and insurance Are there mandatory rules for obtaining trial subjects’ consent to participate? Must sponsors arrange personal injury insurance to a particular limit? For clinical trials on medicinal products, consent must be obtained from all trial subjects according to the Medicinal Products Act. Furthermore, the sponsor of the clinical trial for medicinal products must guarantee financial protection for potential damages or reimbursements, through insurance or otherwise. For medical devices, MPA Regulations LVFS 2003:11 on medical devices and LVFS 2001:5 on active implants require that clinical trials are conducted in accordance with the Declaration of Helsinki, which requires consent from all trial subjects. Marketing authorisationTime frame How long does it take, in general, to obtain an authorisation from application to grant, what fees are payable and what is the normal period of validity of the authorisation? In Sweden, being a part of the EU, an application to obtain market authorisation for medicinal products can be made by four different procedures; - a centralised procedure; - a mutual recognition procedure; - a decentralised procedure; and - a national procedure. In the centralised procedure, the assessment is made by the two national competent authorities appointed by the Committee for Veterinary Medicinal Products or the Committee for Medicinal Products for Human Use. The assessment shall be completed within 210 days. The final opinion is forwarded to the EU Commission for decision. Authorisation of medicinal products via the centralised procedure will entitle the companies in question to sell these products throughout the European Economic Area (EEA). By the mutual recognition procedure, a company may request that an existing national authorisation shall be recognised in other EEA countries. The application is assessed by the competent authority where authorisation has already been granted (reference member state (RMS)) and the competent authority in the country where the authorisation shall be extended (concerned member state (CMS)). The total processing time may not exceed 90 days. The general application fee for a complete application is 120,000 Swedish kronor when Sweden is the CMS and 200,000 Swedish kroner when Sweden is the RMS. An extension of an existing authorisation is 200,000 Swedish kronor if Sweden is the RMS or 65,000 Swedish kronor if Sweden is the CMS. There is also a yearly fee, in general, amounting to 51,000 Swedish kronor for authorised medicinal products. The decentralised procedure is applicable in cases where a company wishes to obtain marketing authorisations in a number of EEA countries for a medicinal product that has no previous authorisation. The application is assessed and approved by an RMS selected by the company and approved concurrently by the selected countries (CMS). The assessment shall be completed within 210 days. The application fees are the same as for the mutual recognition procedure. Through the national procedure, a right to marketing in one single country only can be obtained. The assessment by the MPA shall be completed within 210 days after the MPA has validated the application as complete (the validation period is 14 days). The general application fee is 500,000 Swedish kronor, an extension of an existing authorisation amounts to 200,000 Swedish kronor, and the yearly fee amounts to 51,000 Swedish kronor. There is no requirement for marketing authorisation for medical devices. For some categories of medical devices, both the company and the product must, however, be registered with the MPA. The review period is approximately two months from the time a complete application is received. According to the Ordinance on Medical Devices, the company registration fee is 2,150 Swedish kronor per year. Annual registration fees for products are as follows: - for 10 products: 1,000 Swedish kronor; - for 100 products: 2,000 Swedish kronor; - for 500 products: 5,000 Swedish kronor; and - for more than 500 products: 10,000 Swedish kronor. What protection or exclusivities apply to the data submitted by originators to gain initial approval and, on variation or new application, to add indications or pharmaceutical forms? Data exclusivity is regulated by EU Regulation (EC) No. 726/2004; see the EU chapter.Freedom of information To what extent and when can third parties make freedom of information applications for copies of research data submitted by applicants for authorisation to market medicinal products or medical devices? This is regulated by EU Regulation (EC) No. 726/2004; see the EU chapter.Regulation of specific medicinal products Are there specific rules for approval, and rewards or incentives for approval, of particular types of medicinal products, such as traditional herbal and homeopathic products, biologicals and biosimilars, controlled drugs, orphan drugs and those for paediatric use? MPA Regulation HSLF-FS 2017:75 shall be complied with when registering homeopathic medicinal products. The Regulation is based on articles 14 and 15 of the Medicinal Products Directives. As for herbal medicinal products (ie, medicinal products in which the active ingredient consists exclusively of herbal materials or herbal preparations), these also fall within the scope of the Medicinal Products Directives. Furthermore, MPA Regulation LVFS 2006:3 applies. When it comes to biologicals and biosimilars, the criteria for approval is specified in various guidance papers issued by the EMA. As regards orphan drugs and products for paediatric use, see the EU chapter.Post-marketing surveillance of safety What pharmacovigilance or device vigilance obligations apply to the holder of a relevant authorisation once the product is placed on the market? For medical devices, authorisation holders are required to continuously monitor how their products work in practical use and are obliged to report accidents and incidents when there is a suspicion that the medical device may be involved in the event, according to the Medical Devices Directives, which are implemented by MPA Regulations LVFS 2003:11, 2001:5 and 2001:7. Authorisation holders must also report any corrective safety measures on products that have been placed on the market. For medicinal products, there is a requirement to update product information in relation to new knowledge. In cases of non-compliance, the MPA may send a request regarding post-authorisation control of a medicinal product with demands for updates. Avoiding answering such a request might result in an injunction and other consequences, such as deregistration of the product. Furthermore, there is a requirement for periodic safety update recording in accordance with EU Regulation No. 1235/2010, Directive 2010/84/EU and Commission Implementing Regulation (EU) No. 520/2012, implemented by MPA Regulation LVFS 2012:14. See the EU chapter for more details regarding periodic safety update recording.Other authorisations What authorisations are required to manufacture, import, export or conduct wholesale distribution and storage of medicinal products and medical devices? What type of information needs to be provided to the authorities with an application, what are the fees, and what is the normal period of validity? For medicinal products, a licence from the MPA is required for the manufacturing, import from and export to a country outside the EEA of medicinal products according to the Medicinal Products Act. The requirements for such authorisation are included in MPA Regulation LVFS 2004:7. For example, the application needs to include: - general information regarding the applicant (such as name, registration certificate and billing address); - whether the application concerns a certain medicinal product or medicinal products in general; - the form of medicinal product or products; - the location of the premises; - details regarding the premises and equipment; - a description of potential contract manufacturing or contractual analysis; and - a proposal for an expert or adviser and his or her curriculum vitae. A decision on an application shall in general be made by the MPA within 30 days of the submission of a complete application (this period can be prolonged to 90 days). The general application fee for manufacturing is 65,000 Swedish kronor and the yearly fee is, in general, 60,000 to 80,000 Swedish kronor. The licence is valid for as long as the yearly fees are paid; however, not for a period longer than that indicated in the decision. For medical devices, manufacturers are obliged to register certain forms of medical devices with the MPA in accordance with that outlined under section 3 (the term ‘manufacturer’ also includes import of products outside the EEA). There is, however, no licence required for manufacturing or importing medical devices. Naturally, and in accordance with the Medical Devices Directives, medical devices with the appropriate CE marking may be exported freely within the EEA. Countries outside the EEA may, however, request a ‘free sales certificate’, which ensures that the product may be exported without any legal restrictions. The MPA can issue such certificates. The application fee is 950 Swedish kronor. The period of validity is commonly three years or the time period of the CE marking.Sanctions What civil, administrative or criminal sanctions can authorities impose on entities or their directors and officers for breach of the requirements concerning controlled activities? The MPA has the authority to issue injunctions and prohibitions necessary to ensure compliance with the Medicinal Products Act and Medical Devices Act, and may combine such injunctions with a penalty fine. As for criminal sanctions, violations of the Medicinal Products Act and the Medical Devices Act are penalised with a fine or imprisonment for a maximum of one year.Exemptions What, if any, manufacture and supply of medicinal products is exempt from the requirement to obtain an approval to market? There is an exemption from the marketing authorisation requirement for advanced therapy medicinal products defined in article 2 of EU Regulation (EC) No. 1394/2007, which are produced in Sweden in accordance with a non-routine procedure, for a certain patient in accordance with a prescription, and which are used in Swedish hospitals. A licence is required in accordance with the Medicinal Products Act and MPA Regulation LVFS 2011:3. For unlicensed medicinal products, see question 27.Parallel trade Are imports allowed into your jurisdiction of finished products already authorised in another jurisdiction, without the importer having to provide the full particulars normally required to obtain an authorisation to market? What are the requirements? Parallel import of medicinal products from other EEA countries to Sweden (which have been approved in the other EEA country through the national procedure, the mutual recognition procedure or the decentralised procedure) is allowed but requires authorisation from the MPA in accordance with Regulation LVFS 2012:19, and must comply with the labelling requirements in the Regulation. Medicinal products that have been approved through the central procedure may instead be parallel distributed, which is authorised by the EMA; see the EU chapter for more details. Parallel import of medical devices does not require authorisation from the MPA. However, all labelling and instructions for use of medical devices must be written in Swedish (MPA Regulations LVFS 2001:5, LVFS 2003:11 and LVFS 2001:7). What are the main requirements relating to variation of authorisations for medicinal products and medical devices? EU Regulation (EC) No. 1234/2008 regulates variations to a marketing authorisation for approved medicinal products; see the EU chapter. This is not applicable to medical devices.Renewal What are the main requirements relating to renewal of authorisations for medicinal products and medical devices? A marketing authorisation for medicinal products is valid for five years and may be renewed after this period. One renewal after five years is usually sufficient for continued validity until further notice; however, the authority may, for safety reasons, decide that a further renewal is required. The application for a renewal must be received by the MPA no later than nine months before the renewal date for medicinal products for human use, and six months before the renewal date for veterinary medicinal products. The application must include documentation regarding the efficacy, safety and quality (including detailed pharmacovigilance data) as well as a list of all changes made since the first authorisation or last renewal. This is not applicable to medical devices.Transfer How easy is it to transfer the existing approvals or rights to market medicines and medical devices? How long does this take in general? Application for transfer requires submission of an application form (available on the MPA’s website), which shall be accompanied by a wholesale licence for the new marketing authorisation holder, proof of establishment of the new marketing authorisation holder, summary of product characteristics and patient information leaflet and labelling text with tracked changes (if applicable), the latest approved version of the mock-ups and the new final version (if applicable). The time period of assessment by the MPA is three months. This is not applicable to medical devices. RecallDefective and unsafe products What are the normal requirements for handling cases of defective or possibly unsafe products, including approvals required for recall and communication with health professionals? Manufacturers of medical devices are obliged to report serious incidents with CE-marked devices in Sweden to the MPA, according to MPA Regulations LVFS 2001:5, LVFS 2003:11 and LVFS 2001:7 (and the corresponding Medical Device Directives). The manufacturer shall also be informed of corrective safety measures that are taken by the manufacturer, including recalls (field safety corrective actions). Requirements on the vigilance reporting system are to be found in the EU Commission Guide MEDDEV 2.12/1. For medicinal products, according to the Medicinal Products Act, the MPA is authorised to make decisions regarding their recall. The provisions regarding recall in the Medicinal Products Act are based on the Medicinal Products Directives. Summarise the rules relating to advertising and promotion of medicinal products and medical devices, explaining when the provision of information will be treated as promotional. Do special rules apply to online advertising? The Medicinal Products Act contains specific provisions on marketing of medicinal products, while the Marketing Practices Act relates to marketing in general (thus, including marketing of medicinal products and medical devices). The new EU Regulations 2017/745 and 2017/746 on medical devices prescribe a prohibition on misleading marketing of medical devices. In short, the definition ‘advertising of medicinal products’ described in the Medical Products Directives corresponds to the interpretation of when the provision of information will be treated as promotional according to the Medicinal Products Act. In addition, MPA Regulation LVFS 2009:6 lists several measures that specifically should be included in the definition of marketing of medicinal products. MPA Regulation LVFS 2009:6 also lists several measures that are not to be deemed as marketing of medicinal products. These measures also correspond to the measures mentioned in the Directives; see the EU chapter. The Marketing Practices Act applies to any kind of marketing, including online marketing. Under the Marketing Practices Act, the term ‘advertising’ is seen as part of the broader term ‘marketing’. Even the sale itself, even though entirely passive, is considered to be a marketing measure. In addition, measures that aim to promote the supply of products are included in the definition. The LER Rules by LIF also include rules regarding information of medicinal products. Further, if a company is subject to the LER Rules, it will be able to apply for a prior permission from the Swedish Pharmaceutical Industry’s Information Examiner Committee (IGN) to provide information regarding the medicinal product on a special website. The information provided on the website has to be reviewed by the IGN before it is published and before any changes can be made. Due to the prohibition of advertising of medicinal products directly towards consumers, companies are not allowed to refer to, or in any way promote, their informational website. This means that consumers will have to find the website on their own.Inducement What regulations exist to discourage the provision of inducements to healthcare professionals to prescribe, sell, supply or recommend use of a particular medicinal product or medical device? In addition to general criminal rules on bribes that follow from the Swedish Penal Code (1962:700), the LER Rules provide for specific regulations relating to inducements to healthcare professionals in regard to medicinal products. Any form of cooperation between healthcare professionals and pharmaceutical companies where there has been some kind of remuneration shall be documented. Donations made by the company are only permitted if they are supporting research and development. The only gifts that are permitted are informational and educational material, under the condition that the material is of low value, directly relevant to the practice of the recipient and directly beneficial to the care of patients. Items of medical utility may be provided for purposes of educating employees and for the care of patients under the condition that the item is of low value and not such that it is routinely used in the recipient’s business. Furthermore, it is not permitted to provide healthcare professionals with an inexpensive gift unrelated to the practice of medicine on an infrequent basis in acknowledgement of significant national, cultural or religious holidays. For medical device companies, according to the cooperation agreement entered into with, inter alia, LIF, it is not permitted to offer benefits, gifts or other compensation to healthcare professionals. Gifts offered to medical entities (such as hospitals) that could be considered as indirect gifts to the healthcare professionals working within the medical entity are, accordingly, also prohibited. Donations may never be offered or requested to fund healthcare’s internal or regular activities. Donations to healthcare are allowed only if they are made to support research and development and under the condition that the donation is transparent, well-documented and in accordance with the cooperation agreement and its intentions. There is a specific rule in the industry code stating that ‘donations and grants to healthcare shall not be connected to past, present or potential future use, recommendation, sale or prescription of the donor’s products or services, and may not constitute an inducement to recommend, prescribe, purchase, supply, sell or administer specific medicinal products’.Reporting transfers of value What requirements apply to recording and publishing details of transfers of value to healthcare professionals and organisations by companies marketing medicinal products or medical devices? LIF’s ethical rules correspond to the European Federation of Pharmaceutical Industries and Associations’ Discloser Code in this matter. Direct or indirect transfers of value, whether in cash, in kind or otherwise, made for promotional purposes or otherwise, in connection with the development and sale of prescription-only medicinal products exclusively for human use, to a healthcare professional or organisation shall be recorded and published by the pharmaceutical company. In accordance with the cooperation agreement between, inter alia, LIF and the trade association, Swedish Medtech, the principle of documentation applies to (connected) medical device companies in regard to value transfers. These companies are, therefore, obliged to document information about value transfers, but they do not have to publish this information. Enforcement of advertising rulesEnforcers Describe the bodies involved in monitoring and ensuring compliance with advertising controls for medicinal products and medical devices, distinguishing between any self-regulatory framework and control by the authorities. As regards law enforcement, the Swedish Medical Products Agency is responsible for the supervision of compliance with the Medicinal Products Act and the Medical Devices Act. The Swedish Marketing Practices Act is enforced by the Swedish Consumer Agency. For the self-regulatory LIF, the IGN and the Information Practices Committee have a duty to ensure LIF members’ compliance with the LER Rules.Sanctions What are the possible financial or other sanctions for breach of advertising and promotional controls for medicinal products or medical devices? The MPA is entitled to demand information and issue orders and prohibitions necessary to ensure the compliance with the Medicinal Products Act, the Medical Devices Act and any regulations issued based on the acts in question. Such demands, orders and prohibitions can be coupled with a fine. Sanctions available under the Marketing Practices Act consist of prohibitions or orders coupled with a penalty fine, fines for disruptive marketing practices and damages. Pricing and reimbursementPricing What are the controls imposed on pricing of medicines and medical devices and reimbursement by national social security systems that are applicable to manufacturers, distributors and pharmacists? The Dental and Pharmaceutical Benefits Agency (TLV) is responsible for deciding whether a pharmaceutical product or medical device should be eligible for reimbursement and included in the Swedish benefits scheme. The TLV is responsible for setting the purchase and selling price of such products. These decisions are made in accordance with the Act on Pharmaceutical Benefits (2002:160). Prices are based on an ethical platform with three basic principles: - the human value principle; - the need and solidarity principle; and - the cost-effectiveness principle. The Swedish medical benefit scheme consists of two parts: subsidising of medicinal products and medical devices, and a ‘high-cost threshold’. Sweden applies a high-cost threshold for prescription medicinal products and medical devices, which means that patients only have to pay for such products up to a certain threshold; all prescription medicinal products and medical devices are free thereafter. The high-cost threshold starts to apply after purchases amounting to 1,150 Swedish kronor for prescription medicinal products and medical devices during a 12-month period. However, not all products are included in the high-cost threshold scheme, although the scheme includes numerous types of medicinal products and medical devices. Off-label use and unlicensed productsOff-label use May health professionals prescribe or use products for ‘off-label’ indications? May pharmaceutical companies draw health professionals’ attention to potential off-label uses? The MPA recommends that products that have been authorised for a specific indication are used if available. However, as a general rule, doctors have the right to freely prescribe or use products they deem fit for a particular purpose, including for ‘off-label’ indications, if such use can be motivated based on scientific findings and proven experience. Certain limitations apply to, inter alia, narcotic pharmaceutical products authorised for the treatment of ADHD. Pharmaceutical companies have to be careful in drawing health professionals’ attention to potential off-label uses, as the provision of such information would likely be considered as marketing. For the restrictions on marketing of medicinal products and medical devices, see questions 20 and 21.Unlicensed products What rules apply to the manufacture and importation and supply to healthcare providers of unlicensed medicines or medical devices? Unlicensed medicinal products (ie, medicinal products that have not been granted marketing authorisation by the MPA), may, under certain circumstances, be dispensed after obtaining a special licence from the MPA if there is a need that cannot be satisfied with approved medicinal products on the market. The licence may apply to a certain patient (individual licence) or to one or more healthcare entities (general licence). Furthermore, there is a separate licence to be obtained for the manufacturing of extempore medicinal products (ie, non-standardised medicinal products to be produced by a pharmacy for a certain patient or animal, which is regulated by MPA Regulation LVFS 2010:12 (for extempore pharmacies) or LVFS 2009:8 (for standard pharmacies)). Hospitals may manufacture extempore medicinal products without a licence from the MPA, but must notify the MPA of their supply of medicinal products to the public. The manufacturing of extempore medicinal products that are produced for a certain patient but not for a certain occasion (ie, stock preparations of extempore medicinal products) also requires a licence from the MPA according to Regulation LVFS 2004:7.Compassionate use What rules apply to the establishment of compassionate use programmes for unlicensed products? Compassionate use programmes (CUPs) for unlicensed products can be established in Sweden in accordance with EU Regulation (EC) No. 726/2004 for a group of patients with a life-threatening, chronically or seriously debilitating disease, which cannot be treated satisfactorily by currently authorised medicinal products. The medicinal product concerned must either be the subject of an application for a marketing authorisation or be undergoing clinical trials. The manufacturer or the applicant for market authorisation must apply to the MPA before establishing a CUP. The application is free of charge and can be made through a standard form, which can be obtained from the MPA’s website. Patients participating in the CUP must be provided the product free of charge. Sale and supplyRegulation Are there special rules governing the dispensing or sale of particular types of medicinal products or medical devices? To dispense or sale prescription-free medicinal products or medical devices, the Trade with Prescription Free Medicinal Products Act (2009:730) applies. For dispensing or sale of prescription medicinal products and medical devices, the Trade with Prescription Medicinal Products Act (2009:366) applies as well as MPA Regulation LVFS 2009:8. Each respective act specifies which medicinal products and medical devices can be sold under the Act. Both the dispensing or sale of prescription-free medicinal products or medical devices, and the dispensing or sale of prescription medicinal products and medical devices, requires authorisation from the MPA.Online supply What laws and guidelines govern online dispensing, sale and supply of medicinal products and medical devices? There are no additional laws or guidelines relating to e-pharmacies. Update and trendsForthcoming legislation and regulation Is there any current or foreseeable draft legislation or other rules that will affect the regulation of pharmaceuticals and medical devices? What is likely to change, and what steps need to be taken in preparation?Forthcoming legislation and regulation31 Is there any current or foreseeable draft legislation or other rules that will affect the regulation of pharmaceuticals and medical devices? What is likely to change, and what steps need to be taken in preparation? The MPA has recently been tasked by the government with establishing a structure for cooperation between national players within the healthcare sector regarding medicine shortages and with further developing the MPA’s supply of information during a period when a medicine is not accessible on the Swedish market. The MPA has also been tasked with conducting a pilot study in which a risk-benefit assessment of a pharmaceutical product of the MPA’s choosing, that is commonly prescribed or used for ‘off-label’ indication, will be carried out. The purpose of the pilot study is to assess whether the MPA should start to continuously conduct risk-benefit assessments of common off-label products and to suggest a process for such assessments. In September 2019, Sweden’s plan to join the impending International Horizon Scanning Initiative (IHSI) was announced. IHSI is an international cooperation seeking to identify unauthorised innovative medicinal products. The cooperation, expected to start in late October 2019, will inform decision-making on treatment and budgets in the participating countries. IHSI is a good example of a broader trend of expanding international cooperation on medicinal products.	2	12	1	0	0	0	0.477842	1	7,474
A few years back, the United States government and the American Medical Association developed a new system of diagnostic coding for classifying diseases and disorders. It was called ICD 10, an acronym for International Classification of Disease, and the ‘10’ is the edition number. Classifying a condition like scoliosis is important because it clearly communicates to health-care professionals what type of scoliosis they are dealing with; this is especially important in conditions, like scoliosis, that can take many forms. Before we go into the specific codes for scoliosis, let’s first take a look at what goes into classifying the condition, such as time of diagnosis, causation, and curvature location. Table of Contents When a patient’s scoliosis is classified, when their condition was first diagnosed is what the final classification is based on. In other words, if a patient was first diagnosed with scoliosis when they were a teenager, but as the condition was mild, they didn’t seek out active treatment until well into adulthood, the case would still be classed as adolescent scoliosis, not adult scoliosis. This is important because the reason behind the original onset of a condition or disease helps indicate what form of treatment would be most effective. Particularly with scoliosis, as a progressive condition, when it’s first diagnosed is even more important because condition characteristics can change so substantially over the years. Determining causation is not an easy thing with scoliosis. The condition’s main form, adolescent idiopathic scoliosis, has no known single cause, which is why it’s classified as ‘idiopathic’. However, there are some forms of the condition with known causes, such as congenital, neuromuscular, degenerative and traumatic, and the ICD 10 codes will reflect the cause, if known. Location of the Curvature There are three main sections of the spine: cervical (upper back and neck), thoracic (middle back), and lumbar (lower back). While scoliosis most commonly develops in the thoracic region, it can develop anywhere along the spine, which is why location is another important classification point. Now that we’ve explored the main condition characteristics that go into classifying scoliosis and finding the right code, let’s take a look at some of the most commonly used ICD 10 codes for scoliosis. As so many cases of scoliosis don’t have known causes, the idiopathic condition codes are most commonly used. Adolescent Idiopathic Scoliosis (code M41.12): as mentioned earlier, scoliosis is most commonly diagnosed between the ages of 10 and 18. This group represents approximately 80 percent of diagnosed cases, and there is no known single cause with this form. Scoliosis isn’t always easy to catch, especially in its milder forms or early in the condition’s progression. With adolescents, pain is rarely present, making it more difficult to notice, and postural changes are often subtle and would only be noticed by a specialist who knows how to recognize those subtle signs. Infantile Idiopathic Scoliosis (code M41.00): infantile idiopathic scoliosis is defined as scoliosis diagnosed in infants between birth and the age of 3. Again, this form is idiopathic, so causation is unknown. While some cases of infantile idiopathic scoliosis resolve on their own, for those that don’t, as growth is the main trigger for progression, these infants face the likelihood that their curvature will progress to severe levels in later life. Juvenile Idiopathic Scoliosis (code M41.11): juvenile idiopathic scoliosis is defined as scoliosis diagnosed in individuals between the ages of 3 and 9 with no known single cause. Again, as growth is such a big trigger for the condition’s progression, this age group faces a high risk of progression because they have so much growth yet to go through. Additional Idiopathic Scoliosis Conditions (code M41.2): this code is used for any other conditions that remained undetected prior to the patient reaching skeletal maturity. Most often, skeletal maturity is considered to be reached around the age of 18, but of course, this isn’t exact and differs case by case. Cases of degenerative or adult ‘de novo’ scoliosis would also fall into this category. These cases are classed as ‘de novo’ because they have developed fresh in adulthood, after skeletal maturity has been reached, with no prior history of having the condition. These types of cases often involve patients who are over 40 and facing degenerative changes to the spine and the discs that cushion the spine’s individual vertebrae. Congenital Scoliosis (code Q76.3): congenital scoliosis is one of the condition’s forms with a known cause, which is a congenital bone malformation, like a hemivertebra, that’s present at birth. In congenital scoliosis, there is a malformed vertebrae that throws off the alignment of the spine. In a healthy spine, the vertebrae are stacked on top of one another like rectangular bricks; in congenital scoliosis, picture one of those vertebrae as triangular in shape, and you can imagine how much that would throw off that stack of vertebrae and cause the spine to slip to the side. Congenital Spinal Deformity (code Q67.5): this code is used for patients with congenital scoliosis that wasn’t caused by a bone malformation and for other cases of congenital scoliosis that don’t fit into another code. Neuromuscular Scoliosis (code M41.4): neuromuscular scoliosis is another form of the condition with a known cause. This code is used to classify scoliosis that develops as a secondary complication of neuromuscular disorders; these would include cerebral palsy, muscular dystrophy, spina bifida, etc. Obviously, there are many more codes that go with the different forms of scoliosis, and conditions with specific scoliosis-related complications such as cardiac issues or lung impairment have their own codes to further specify the condition. When it comes to documenting spinal conditions, ICD-10 codes play a crucial role. For dextroscoliosis, you would typically use the ICD-10 code M41.9 for the diagnosis. This code, part of the ICD-10-CM code for scoliosis, can be employed for various types of scoliosis, including dextroscoliosis. If a patient has a history of scoliosis, the ICD-10 code for a history of scoliosis (hx of scoliosis ICD-10) may be used to capture their medical background. Furthermore, lumbar levoscoliosis, a specific type of spinal curvature, has its distinct ICD-10 code for accurate diagnosis. It's crucial to differentiate between the types of scoliosis since they might result from various causes, including postural, congenital factors, bony malformations, postradiation scoliosis following radiation therapy, and postprocedural scoliosis after certain medical interventions. In some cases, scoliosis may be associated with other medical conditions, such as kyphoscoliotic heart disease, necessitating comprehensive documentation to ensure accurate treatment and care. When assigning ICD-10 codes for scoliosis, healthcare professionals consider factors such as the type and location of the curvature, with codes specific to conditions like cervical lordosis and thoracolumbar lordosis to accurately document the patient's diagnosis. When a condition is first diagnosed, it has to be comprehensively assessed. This comprehensive assessment involves looking at a number of characteristics involving the patient and their condition and documenting those findings. The current procedural terminology (CPT) used by the American Medical Association and the ICD are working to classify medical diseases and conditions as thoroughly and consistently as possible. Having a common language and system of coding used to define and classify scoliosis helps ensure a certain level of patient care, regardless of where that patient seeks treatment. Initial scoliosis coding and sequencing will depend upon the doctor that first diagnoses and documents the condition. If there is a consistent system for classifying scoliosis, different doctors, specialists, and health-care professionals can have a common understanding of the form of the condition they are treating and the requirements that have to be met to accurately define and classify it. So we know that complete and accurate coding is beneficial to the team of health-care professionals treating a specific patient, but it is also necessary to ensure that an effective treatment plan can be designed and implemented. Through comprehensive coding, that team will know everything they need to know about the condition to be able to design a customized treatment plan. A treatment plan that is customized accordingly will address the individual characteristics of the patient and the form of scoliosis they are dealing with. As we have seen, scoliosis is not a simple condition to treat as it ranges widely in severity and can take on many forms. Having a comprehensive and accurate coding system in place addresses this complexity and establishes a method for streamlining the diagnosis and treatment process amongst health-care professionals. Understanding ICD-10 codes for scoliosis is essential when it comes to proper medical documentation. These codes help classify and identify different scoliosis types, including levoconvex scoliosis, and various scoliosis curvature types. By utilizing the appropriate ICD-10 codes, healthcare professionals can accurately categorize and communicate the specific nature of the patient's scoliosis, facilitating effective diagnosis and treatment. A person might think, “Scoliosis is scoliosis. A crooked spine is a crooked spine,” but as we have learned, there are many different types of crooked spines, and these different types necessitate different forms of treatment. A necessary step in defining and classifying scoliosis is taking into account when a patient was first diagnosed with the condition, not necessarily when they first started treatment. Cause of the condition, whether known or unknown, is important because it tells us if we are dealing with a ‘typical’ or ‘atypical’ form of the condition. Where along the spine the scoliosis develops is also important because it helps us further classify the condition and know where to focus our adjustment efforts. The types of ICD 10 codes for scoliosis are most important in terms of treatment efficacy. Clearly, we want the best for our patients, and here at the Scoliosis Reduction Center, out treatment approach centers around customization. Having a system of codes and terminology in place helps us understand another doctor’s assessment and diagnosis and also helps us comprehensively assess and diagnose the patients that walk through our doors. Regardless of where you are in the progressive line of your condition, seeking active treatment is always the best choice. Together, we can help guide patients on how best to integrate their condition as positively as possible into their life and future goals.	4	5	0	0	0	9	0.884037	9	2,377
December 17, 2012 Coding for Peripheral Neuropathy For The Record Vol. 24 No. 23 P. 25 Peripheral neuropathy involves damage to the peripheral nerves, which send information to and from the brain and spinal cord to other parts of the body. Damage to a peripheral nerve may affect communication between the brain and other body parts and may cause problems with muscle movement and sensation in the arms and legs. The condition can cause problems to a single peripheral nerve (mononeuropathy), multiple nerves in different areas (multiple mononeuropathy), or many nerves throughout the body (polyneuropathy). Additionally, it may affect sensory, motor, or autonomic nerves. Peripheral neuropathy may be the result of diabetes, traumatic injuries, infections, metabolic problems, and toxins, with diabetes being the most common cause. Symptoms of peripheral neuropathy vary depending on the type of nerve affected. Common signs and symptoms include numbness and tingling in feet or hands; burning pain in the arms and legs; sharp, jabbing, or electriclike pain; extreme sensitivity to touch; lack of coordination; muscle weakness or paralysis if motor nerves are affected; and bowel or bladder problems if autonomic nerves are affected. Mononeuropathy or mononeuritis is classified to ICD-9-CM categories 354 and 355. Additional digits will identify the specific nerve involved as follows: • 354.0, Carpal tunnel syndrome; • 354.1, Other lesion of median nerve; • 354.2, Lesion of ulnar nerve; • 354.3, Lesion of radial nerve; • 354.4, Causalgia of upper limb; • 354.5, Mononeuritis multiplex; • 354.8, Other mononeuritis of upper limb; • 354.9, Mononeuritis of upper limb, unspecified; • 355.0, Lesion of sciatic nerve; • 355.1, Meralgia paresthetica; • 355.2, Other lesion of femoral nerve; • 355.3, Lesion of lateral popliteal nerve; • 355.4, Lesion of medial popliteal nerve; • 355.5, Tarsal tunnel syndrome; • 355.6, Lesion of plantar nerve; • 355.71, Causalgia of lower limb; • 355.79, Other mononeuritis of lower limb; • 355.8, Mononeuritis of lower limb, unspecified; and • 355.9, Mononeuritis of unspecified site. Peripheral neuropathy that is not further specified as being caused by an underlying condition is assigned to code 356.9. Autonomic neuropathy not further specified is classified to code 337.9. If either peripheral or autonomic neuropathy is caused by diabetes, then a code from subcategory 250.6 will be sequenced first followed by code 357.2 for polyneuropathy in diabetes or code 337.1 for peripheral autonomic neuropathy. Diabetic peripheral neuropathy is one of the more serious complications of long-term diabetes. It typically affects patients with type 1 diabetes more frequently than those with type 2 and occurs more often in men. It’s thought to evolve from damage to capillaries in the extremities caused by the long-term effects of poorly controlled or uncontrolled blood glucose. This vascular damage injures the peripheral nerves. Patients describe the pain as burning, tingling, and occasionally stabbing. If a patient is admitted with a diabetic neuropathy or has neuropathy caused by diabetes, the diabetic code from category 250 must be sequenced as the principal diagnosis followed by the manifestations as secondary diagnoses. Conditions are coded in this manner even though the ICD-9-CM alphabetic index may not indicate dual coding (AHA Coding Clinic for ICD-9-CM, 1991, third quarter, page 8). In other words, the physician must state a cause-and-effect relationship between the manifestation and the diabetes before it can be coded as a diabetic condition. A patient with diabetes can develop neuropathy that is unrelated to the diabetes. If this is the case, the unspecified diabetes code will be assigned as well as the appropriate code for the neuropathy. Sequencing of the two conditions will depend on the circumstances of admission. However, if the physician establishes a link between the diabetes and the neuropathy, then it will be coded as a diabetic complication. According to Coding Clinic, if the physician documents “diabetes with neuropathy,” then a cause-and-effect relationship has been established, and it can be coded as a diabetic complication (250.6x + 357.2) (AHA Coding Clinic for ICD-9-CM, 2009, second quarter, page 15). It is not possible to cure neuropathy, but several medications have been found to help ease the pain. Among the most common medications are tricyclic antidepressants such as imipramine; serotonin and norepinephrine reuptake inhibitors, including duloxetine (Cymbalta); certain antiseizure medications, including pregabalin (Lyrica), gabapentin (Neurontin), and carbamazepine (Tegretol); lidocaine patches; and ointments such as ArthriCare and Zostrix (both of which are based on the chemical that gives peppers their heat). Finally, in extreme cases, powerful opioid analgesics such as OxyContin can be helpful, but the addictive aspect of these medications makes them a risky choice. For some patients with diabetic peripheral neuropathy, a physician might apply a transcutaneous electrical nerve stimulation unit or recommend therapies such as biofeedback, acupuncture, hypnosis, meditation, and yoga. Coding and sequencing for peripheral neuropathy are dependent on the physician documentation in the medical record and application of the Official Coding Guidelines for inpatient care. Also, use specific AHA Coding Clinic for ICD-9-CM and American Medical Association CPT Assistant references to ensure complete and accurate coding. — This information was prepared by Audrey Howard, RHIA, of 3M Consulting Services. 3M Consulting Services is a business of 3M Health Information Systems, a supplier of coding and classification systems to more than 5,000 healthcare providers. The company and its representatives do not assume any responsibility for reimbursement decisions or claims denials made by providers or payers as the result of the misuse of this coding information. More information about 3M Health Information Systems is available at www.3mhis.com or by calling 800-367-2447. ICD-10-CM Coding for Peripheral Neuropathy Coding neuropathy in ICD-10-CM is similar to coding it in ICD-9-CM. Upper-limb mononeuropathies are classified to category G56, and lower-limb mononeuropathies go to category G57, with the additional characters identifying the specific nerve and laterality. Polyneuropathy is classified to categories G60 to G65. If the neuropathy is caused by diabetes, then only one combination code is assigned to identify both the diabetes and the neuropathy. ICD-10-CM has combination codes in the diabetes section for the following types of diabetic neuropathy: mononeuropathy, polyneuropathy, autonomic (poly)neuropathy, and amyotrophy. For example, type 1 diabetes mellitus with diabetic polyneuropathy is classified to code E10.42, and type 1 diabetes mellitus with diabetic autonomic (poly)neuropathy is assigned to code E10.43.	4	8	0	0	0	5	0.841961	5	1,616
Managed care is a generic term for various health care payment systems that attempt to contain costs by controlling the type and level of services provided. Health maintenance organization (HMO) is a term that is often used synonymously with managed care, but HMOs are actually a particular type of managed care organization. Health care reform has been an increasingly urgent concern in the United States over the past 40 years. Until recently, the primary source of health care coverage was indemnity insurance, which pays or reimburses the cost of medical services in the event of a person's illness or injury. Indemnity insurance gives health care providers few reasons to use less expensive forms of treatment— the insurance companies generally pay for any treatment deemed necessary by a physician. Presumably, this type of system encourages providers to overuse expensive, unnecessary treatments and diagnostic procedures. Patient co-pays and deductibles attempt to limit excessive use of medical services. Yet costs continue to rise, resulting in insurance companies' frequently raising premium prices. The primary intent of managed care is to reduce health care costs. Emphasis is placed on preventive care and early intervention , rather than care provided after an illness or injury has occurred. The responsibility of limiting services is placed on the service provider rather than the consumer. This limitation is achieved by (a) "gatekeeper" policies that require individuals to get referrals for specialized treatment from their primary physicians;(b) financial incentives (either bonuses or withholding money) for providers to restrict services and contain costs; (c) guidelines requiring adherence by providers at the cost of being dropped from the plan for noncompliance; (d) review of services by the managed care organization and denial of payment if services are considered unnecessary. Health maintenance organizations have been in existence in the United States since the late 1800s. It was not until the 1950s, however, that the government began to encourage the development of HMOs. In 1973, the Health Maintenance Organization Act was passed; and in 1978, a Congressional amendment increased federal aid for HMO development. From 1980 to 1989, enrollment in HMOs increased from 9 million to 36 million Americans. By 1990, 95% of private insurance companies used some form of managed care. In the 1990s, managed care was incorporated into Medicare and Medicaid plans as well. Managed care organizations frequently contract with a group or panel of health care providers. HMOs and PPOs (preferred provider organizations) are examples of these types of contracts. Individuals insured under an HMO or PPO may receive care only from providers on the panel. These providers are expected to deliver services according to specific stipulations. Payment is often subject to utilization review, in which delivery of medical services is scrutinized to determine whether the services are necessary. The review may occur with each episode of treatment, or may be ongoing through the use of a case manager. If the managed care organization thinks that the services were unnecessary, payment is denied. Payment arrangements between managed care organizations and care providers are often made in advance. Capitated payment systems are typically used with large health care facilities that serve many people. The health care provider receives a set amount of money each month based on the number of individuals covered by the plan. The provider may or may not serve that many people in one month. Capitation systems provide a steady, reliable cash flow, but involve some economic risk because the services provided may exceed the dollar amount allotted. Another type of payment system uses case rates. The provider receives a predetermined amount of money per individual on a case-by-case basis. The amount of money reflects the estimated service costs to treat the individual patient's condition. Again, the provider takes the risk that unanticipated services will be required. In the past, mental health services (including substance abuse treatment) were routinely excluded from managed care plans. In the 1970s, some mental health care coverage was required in order to meet federal qualifications. Carve-out plans were developed in the 1990s. These plans essentially create a separate managed care plan for mental health services. Mental health services tend to be covered at a lower rate than general health services and have also been cut back more severely. From 1988 to 1997, mental health care spending decreased by 54%, which reflects cutbacks 670% higher than those for general health care benefits. Mental health care providers are also subjected to higher levels of utilization review than medical care providers. Managed care has been successful in fulfilling its primary purpose of lowering health care costs in the United States. Statistics show drastic decreases in the use of inpatient care and accompanying overall reduction in costs. Many observers, however, would argue that the quality of care has suffered as a result. Individuals have fewer choices regarding the locations where they can receive treatment. If a managed care organization closes, individuals under that plan must switch to other care providers under a new plan, which disrupts ongoing treatment. Care providers often feel that their clients are denied essential care in favor of saving money. Employers have become disillusioned because of increasing disability claims due to employees having received inadequate treatment for illnesses or injuries. In addition to disability claims, inadequate treatment results in hidden costs to employers in terms of lost productivity. Another factor in decreased quality of care involves conflicting loyalties for health care providers. On the one hand, providers want to ensure quality care for their clients. On the other hand, they are encouraged to provide the least amount of care possible in order to receive financial benefits. Just as dishonest practice was suspected in conjunction with indemnity insurance, managed care creates a powerful potential for inappropriately addressing patients' needs. Due to growing popular discontent with managed care organizations, many critics believe that the system will not continue in its current state. No one, however, expects managed care to disappear completely and indemnity plans to rise to their former prominence. Changes are expected to occur as managed care programs begin competing among themselves. Cost and efficiency will no longer be the main selling point; quality of services will take precedence. One researcher has suggested that along with new systems of managed care and continuing systems of indemnity plans, health care providers may even organize and offer services directly to employers, thus eliminating the middlemen. This development would be beneficial to all involved: employers would pay less; providers would be better compensated; and clients would receive better care. See also Case management Horwitz, Allan V. and Teresa L. Scheid, eds. A Handbook for the Study of Mental Health. New York: Cambridge University Press, 1999. Sauber, S. Richard, ed. Managed Mental Health Care: Major Diagnostic and Treatment Approaches. Philadelphia: Brunner/Mazel, 1997. Tuttle, Gayle McCracken and Diane Rush Woods. The Managed Care Answer Book for Mental Health Professionals. Bristol, Pennsylvania: Brunner/Mazel,1997. Gottlieb, Michael C. and Caren C. Cooper. "The Future of Mental Health Care Delivery: Ideals and Realities." Counseling Psychologist 28, no. 2 (2000): 263-266. Reed, Geoffrey M., Ronald F. Levant, Chris E. Stout, Michael J. Murphey, and Randy Phelps. "Psychology in the Current Mental Health Marketplace." Professional Psychology: Research and Practice 32, no. 1 (2001): 65-70. American Association of Health Plans. 1129 20th Street NW, Suite 600, Washington, DC 20036-3421. <http://www.aahp.org> . Department of Managed Health Care. California HMO Help Center, 980 Ninth Street, Suite 500, Sacramento, CA 95814-2725. <http://www.hmohelp.ca.gov> . Medicare. 1-800-MEDICARE. <www.medicare.gov> . Sandra L. Friedrich, M.A.	2	6	2	0	0	0	0.852695	2	1,612
Get the facts about birth control so you can decide which type is right for you. - Birth Control Facts about birth control to help decide which type is right for you. - Type 2 Diabetes Basic facts about type 2 diabetes & risk factors to be aware of. - COPD Get the facts about chronic obstructive pulmonary disease (COPD), including symptoms and complications. - Diabetic Macular Edema Facts about diabetic macular edema, including the different types. - Flu Facts about influenza (flu), including symptoms and vaccines. - GERD Get the facts about gastroesophageal reflux disease (GERD). - HIV/AIDS The differences between HIV & AIDS; signs, symptoms & complications. - Lupus Get the facts about lupus, including symptoms, risk factors, and the different types. - Menopause Facts about menopause, including the stages, symptoms, and types. - Shingles Facts about shingles, including symptoms & possible long-term effects. - View All Care Guides Prepare for your next visit with our extensive library of Care Guides Dr. Louis D Saravolatz has the following 2 specialties - Infectious Disease An infectious disease specialist has specialized training in the diagnosis and treatment of contagious diseases. Infectious diseases, also known as contagious or transmissible diseases, are those that stem from pathogen from a host organism. These infections may spread to other carriers through physical touch, airborne inhalation, bodily fluids or contaminated foods. Infectious disease specialists identify whether the disease is caused by bacteria, a virus, a fungus or a parasite often through blood tests and then determine what course of treatment, if any, is necessary. - Internal Medicine An internist is a physician who focuses on the diagnosis and treatment of conditions that affect the adult population—both acute and chronic. These doctors are often who adults see as their primary physicians because they treat a broad range of illnesses that do not require surgical or specialist interventions. They also work to help a patient maintain optimal health in order to prevent the onset of disease. In addition to treating the common cold and flu, internists also treat chronic diseases like diabetes and heart disease. - Bacterial Endocarditis - Drug Abuse (Substance-Related Addiction Disorders) - Human Immunodeficiency Virus (HIV/AIDS) - Community-Acquired Infections - Bacterial Infections - AIDS/HIV (Acquired Immunodeficiency Syndrome) - Hepatitis C - Sepsis (Blood Poisoning) - Viral Human Hepatitis Showing 5 of 12 In regards to this office, I called as a new patient, with health insurance. The receptionist wanted to start the process by "getting me in the system" - her first question was asking me for my social security number over the phone. She stated it was for insurance purposes. I proceeded to tell her I was uncomfortable giving my SSN over the phone, considering I haven't been there yet, and her respond - "okay, I can't help you." I found this very unprofessional, rude, and offensive. Just for that alone - I do not recommend this place: I will take my business and insurance elsewhere. I've never had anyone ask that. Patients' Choice Award (2012, 2013) Patients' Choice recognition reflects the difference a particular physician has made in the lives of his/her patients. The honor is bestowed to physicians who have received near perfect scores, as voted by patients. Compassionate Doctor Recognition (2012, 2013, 2011) Compassionate Doctor certification is granted to physicians who treat their patients with the utmost kindness. The honor is granted based on a physician's overall and bedside manner scores. On-Time Doctor Award (2014) Vitals On-Time + Promptness Award recognizes doctors with consistent high ratings for timeliness of appointments. The honor is granted based on a physician's overall and promptness scores. 44 Years Experience University Of Michigan Medical School Graduated in 1974 Henry Ford Health System Dr. Louis D Saravolatz accepts the following insurance providers. BCBS Blue Card - BCBS Blue Card PPO - BCBS IL PPO - BCBS MI Blue Care Network HMO Group Enrollees - CIGNA HMO - CIGNA Open Access Plus - CIGNA PPO - First Health PPO - HAP Preferred PPO - Humana Choice POS - Humana ChoiceCare Network PPO - Multiplan PPO - PHCS PPO - PriorityHealth HMO - PriorityHealth Priority PPO - UHC Choice Plus POS - UHC Navigate HMO - UHC Navigate POS - UHC Options PPO - View by Location Locations & DirectionsSt John Hospital And Medical Center, 19251 Mack Ave Ste 333, Grosse Pointe Woods, MI Take a minute to learn about Dr. Louis D Saravolatz in this video. Dr. Louis D Saravolatz is similar to the following 3 Doctors near Grosse Pointe Woods, MI.	2	6	1	0	0	0	0.909043	1	1,086
\|Synonyms\|\|Faecal incontinence, bowel incontinence, anal incontinence, accidental bowel leakage\| \|Diagram showing normal anatomy of anal canal and rectum.\| \|Classification and external resources\| Fecal incontinence (FI), also known as anal incontinence, or in some forms encopresis, is a lack of control over defecation, leading to involuntary loss of bowel contents—including flatus (gas), liquid stool elements and mucus, or solid feces. FI is a sign or a symptom, not a diagnosis. Incontinence can result from different causes and might occur with either constipation or diarrhea. Continence is maintained by several inter-related factors, including the anal sampling mechanism, and usually there is more than one deficiency of these mechanisms for incontinence to develop. The most common causes are thought to be immediate or delayed damage from childbirth, complications from prior anorectal surgery (especially involving the anal sphincters or hemorrhoidal vascular cushions) and altered bowel habits (e.g., caused by irritable bowel syndrome, Crohn's disease, ulcerative colitis, food intolerance, or constipation with overflow incontinence). An estimated 2.2% of community dwelling adults are affected. Fecal incontinence has three main consequences: local reactions of the perianal skin and urinary tract, including maceration (softening and whitening of skin due to continuous moisture), urinary tract infections, or decubitus ulcers (pressure sores); a financial expense for individuals (due to cost of medication and incontinence products, and loss of productivity), employers (days off), and medical insurers and society generally (health care costs, unemployment); and an associated decrease in quality of life. There is often reduced self-esteem, shame, humiliation, depression, a need to organize life around easy access to bathroom and avoidance of enjoyable activities. FI is an example of a stigmatized medical condition, which creates barriers to successful management. People may be too embarrassed to seek medical help, and attempt to self-manage the symptom in secrecy from others. FI is one of the most psychologically and socially debilitating conditions in an otherwise healthy individual, but it is generally treatable. Management may be achieved through an individualized mix of dietary, pharmacologic, and surgical measures. Health care professionals are often poorly informed about treatment options, and may fail to recognize the effect of FI. - 1 Signs and symptoms - 2 Causes - 3 Pathophysiology - 4 Diagnostic approach - 5 Management - 6 Epidemiology - 7 History - 8 Society and culture - 9 Research - 10 See also - 11 References - 12 External links Signs and symptoms FI affects virtually all aspects of peoples' lives, greatly diminishing physical and mental health, and affect personal, social and professional life. Emotional effects may include stress, fearfulness, anxiety, exhaustion, fear of public humiliation, feeling dirty, poor body-image, reduced desire for sex, anger, humiliation, depression, isolation, secrecy, frustration and embarrassment. Some people may need to be in control of life outside of FI as means of compensation. The physical symptoms such as skin soreness, pain and odor may also affect quality of life. Physical activity such as shopping or exercise is often affected. Travel may be affected, requiring careful planning. Working is also affected for most. Relationships, social activities and self-image likewise often suffer. Symptoms may worsen over time. FI is a sign or a symptom, not a diagnosis, and represents an extensive list of causes. Usually, it is the result of a complex interplay of several coexisting factors, many of which may be simple to correct. Up to 80% of people may have more than one abnormality that is contributing. Deficits of individual functional components of the continence mechanism can be partially compensated for a certain period of time, until the compensating components themselves fail. For example, obstetric injury may precede onset by decades, but postmenopausal changes in the tissue strength reduce in turn the competence of the compensatory mechanisms. The most common factors in the development are thought to be obstetric injury and after effects of anorectal surgery, especially those involving the anal sphincters and hemorrhoidal vascular cushions. The majority of incontinent persons over the age of 18 fall into one of several groups: those with structural anorectal abnormalities (sphincter trauma, sphincter degeneration, perianal fistula, rectal prolapse), neurological disorders (multiple sclerosis, spinal cord injury, spina bifida, stroke, etc.), constipation/fecal loading (presence of a large amount of feces in the rectum with stool of any consistency), cognitive and/or behavioral dysfunction (dementia, learning disabilities), diarrhea, inflammatory bowel diseases (e.g. ulcerative colitis, Crohn's disease), irritable bowel syndrome, disability related (people who are frail, acutely unwell, or have chronic/acute disabilities), and those cases which are idiopathic (of unknown cause). Diabetes mellitus is also known to be a cause, but the mechanism of this relationship is not well understood. The functioning of the anal canal can be damaged, traumatically or atraumatically. The resting tone of the anal canal is not the only factor which is important, both the length of the high pressure zone and its radial translation of force are required for continence. This means that even with normal anal canal pressure, focal defects such as the keyhole deformity can be the cause of substantial symptoms. External anal sphincter (EAS) dysfunction is associated with impaired voluntary control, whereas internal anal sphincter (IAS) dysfunction is associated with impaired fine tuning of fecal control. Lesions which mechanically interfere with, or prevent the complete closure of the anal canal can cause a liquid stool or mucous rectal discharge. Such lesions include piles (inflamed hemorrhoids), anal fissures, anal cancer or fistulae. Obstetric injury may tear the anal sphincters, and some of these injuries may be occult (undetected). The risk of injury is greatest when labor has been especially difficult or prolonged, when forceps are used, with higher birth weights or when an midline episiotomy is performed. Only when there is post operative investigation of FI such as endoanal ultrasound is the injury discovered. FI is a much under-reported complication of surgery. The IAS is easily damaged with an anal retractor (especially the Park's anal retractor), leading to reduced resting pressure postoperatively. Since the hemorrhoidal vascular cushions contribute 15% of the resting anal tone, surgeries involving these structures may affect continence status. Partial internal sphincterotomy, fistulotomy, anal stretch (Lord's operation), hemorrhoidectomy or transanal advancement flaps may all lead to FI post operatively, with soiling being far more common than solid FI. The "keyhole deformity" refers to scarring within the anal canal and is another cause of mucus leakage and minor incontinence. This defect is also described as a groove in the anal canal wall, and may occur after posterior midline fissurectomy or fistulotomy, or with lateral IAS defects. Rare causes of traumatic injury to the anal sphincters include military or traffic accidents complicated by pelvic fractures, spine injuries or perineal lacerations, insertion of foreign bodies in the rectum, and sexual abuse. Nontraumatic conditions causing anal sphincter weakness include scleroderma, damage to the pudendal nerves and IAS degeneration of unknown cause. Radiation induced FI may involve the anal canal as well as the rectum, when proctitis, anal fistula formation and diminished function of internal and external sphincter occur. Irradiation may occur during radiotherapy, e.g. for prostate cancer. Many people with FI have a generalized weakness of the pelvic floor, especially puborectalis. A weakened puborectalis leads to widening of the anorectal angle, and impaired barrier to stool in the rectum entering the anal canal, and this is associated with incontinence to solids. Abnormal descent of the pelvic floor can also be a sign of pelvic floor weakness. Abnormal descent manifests as descending perineum syndrome (>4 cm perineal descent). This syndrome initially gives constipation, and later FI. The pelvic floor is innervated by the pudendal nerve and the S3 and S4 branches of the pelvic plexus. With recurrent straining, e.g. during difficult labour or long term constipation, then stretch injury can damage the nerves supplying levator ani. The pudendal nerve is especially vulnerable to irreversible damage, (stretch induced pudendal neuropathy) which can occur with a 12% stretch. If the pelvic floor muscles lose their innervation, they cease to contract and their muscle fibres are in time replaced by fibrous tissue, which is associated with pelvic floor weakness and incontinence. Increased pudendal nerve terminal motor latency may indicate pelvic floor weakness. The various types of pelvic organ prolapse (e.g. external rectal prolapse, mucosal prolapse and internal rectal intussusception & solitary rectal ulcer syndrome) may also cause coexisting obstructed defecation. The rectum needs to be of a sufficient volume to store stool until defecation. The rectal walls need to be "compliant" i.e. able to distend to an extent to accommodate stool. Rectal sensation is required to detect the presence, nature and amount of rectal contents. The rectum must also be able to evacuate its contents fully. There must also be efficient co-ordination of rectal sensation and relaxation of the anal canal. If the sensory nerves are damaged, detection of stool in the rectum is dulled or absent, and the person will not feel the need to defecate until too late. Rectal hyposensitivity may manifest as constipation, FI, or both. Rectal hyposensitivty was reported to be present in 10% of people with FI. Pudendal neuropathy is one cause of rectal hyposensitivity, and may lead to fecal loading/impaction, megarectum and overflow FI. Normal evacuation of rectal contents is 90-100%. If there is incomplete evacuation during defecation, residual stool will be left in the rectum and threaten continence once defecation is finished. This is a feature of people with soiling secondary to obstructed defecation. Obstructed defecation is often due to anismus (paradoxical contraction or relaxation failure of the puborectalis).:38 Whilst anismus is largely a functional disorder, organic pathologic lesions may mechanically interfere with rectal evacuation. Other causes of incomplete evacuation include non-emptying defects like a rectocele. Straining to defecate pushes stool into the rectocele, which acts like a diverticulum and causes stool sequestration. Once the voluntary attempt to defecate, albeit dysfunctional, is finished, the voluntary muscles relax, and residual rectal contents are then able to descend into the anal canal and cause leaking.:37 \|Drug/mechanism of action\|\|Common examples\| \|Drugs altering sphincter tone\| \|Broad spectrum antibiotics\| \|Topical drugs applied to anus (reducing pressure)\| \|Drugs causing profuse diarrhea\| \|Tranquilisers/hypnotics (reducing alertness)\| Central nervous system Continence requires conscious and subconscious networking of information from and to the anorectum. Defects/brain damage may affect the central nervous system focally (e.g. stroke, tumor e.g. spinal cord lesions, trauma, multiple sclerosis) or diffusely (e.g. dementia, multiple sclerosis, infection, Parkinson's disease or drug-induced). FI (and urinary incontinence) may also occur during epileptic seizures. Dural ectasia is an example of a spinal cord lesion that may affect continence. Liquid stool is more difficult to control than formed, solid stool. Hence, FI can be exacerbated by diarrhea. Some consider diarrhea to be the most common aggravating factor. Orlistat is an anti-obesity (weight loss) drug that blocks the absorption of fats. This may give side effects of FI, diarrhea and steatorrhea. This may occur when there is a large mass of feces in the rectum (fecal loading), which may become hardened (fecal impaction). Liquid stool elements are able to pass around the obstruction, leading to incontinence. Megarectum (enlarged rectal volume) and rectal hyposensitivity are associated with overflow incontinence. Hospitalized patients and care home residents may develop FI via this mechanism, possibly a result of lack of mobility, reduced alertness, constipating effect of medication and/or dehydration. The mechanisms and factors contributing to normal continence are multiple and inter-related. The puborectalis sling, forming the anorectal angle (see diagram), is responsible for gross continence of solid stool. The IAS is an involuntary muscle, contributing about 55% of the resting anal pressure. Together with the hemorrhoidal vascular cushions, the IAS maintains continence of flatus and liquid during rest. The EAS is a voluntary muscle, doubling the pressure in the anal canal during contraction, which is possible for a short time. The rectoanal inhibitory reflex (RAIR) is an involuntary IAS relaxation in response to rectal distension, allowing some rectal contents to descend into the anal canal where it is brought into contact with specialized sensory mucosa to detect consistency. The rectoanal excitatory reflex (RAER) is an initial, semi-voluntary contraction of the EAS and puborectalis which in turn prevents incontinence following the RAIR. Other factors include the specialized anti-peristaltic function of the last part of the sigmoid colon, which keeps the rectum empty most of the time, sensation in the lining of the rectum and the anal canal to detect when there is stool present, its consistency and quantity, and the presence of normal rectoanal reflexes and defecation cycle which completely evacuates stool from the rectum and anal canal. Problems affecting any of these mechanisms and factors may be involved in the cause. Identification of the exact causes usually begins with a thorough medical history, including detailed questioning about symptoms, bowel habits, diet, medication and other medical problems. Digital rectal examination is performed to assesses resting pressure and voluntary contraction (maximum squeeze) of the sphincter complex and puborectalis. Anal sphincter defects, rectal prolapse, and abnormal perineal descent may be detected. Anorectal physiology tests assess the functioning of the anorectal anatomy. Anorectal manometry records the pressure exerted by the anal sphincters and puborectalis during rest and during contraction. The procedure is also able to assess sensitivity of the anal canal and rectum. Anal electromyography tests for nerve damage, which is often associated with obstetric injury. Pudendal nerve terminal motor latency tests for damage to the pudendal motor nerves. Proctography, also known as defecography, shows how much stool the rectum can hold, how well the rectum holds it, and how well the rectum can evacuate the stool. It will also highlight defects in the structure of the rectum such as internal rectal intussusception. Dynamic pelvic MRI, also called MRI defecography is an alternative which is better for some problems but not as good for other problems. Proctosigmoidoscopy involves the insertion of an endoscope (a long, thin, flexible tube with a camera) into the anal canal, rectum and sigmoid colon. The procedure allows for visualization of the interior of the gut, and may detect signs of disease or other problems that could be a cause, such as inflammation, tumors, or scar tissue. Endoanal ultrasound, which some consider to be the gold standard for detection of anal canal lesions, evaluates the structure of the anal sphincters, and may detect occult sphincter tears that otherwise would go unseen. Functional FI is common. The Rome process published diagnostic criteria for functional FI, which they defined as "recurrent uncontrolled passage of fecal material in an individual with a developmental age of at least 4 years". The diagnostic criteria are, one or more of the following factors present for the last 3 months: abnormal functioning of normally innervated and structurally intact muscles, minor abnormalities of sphincter structure/innervation (nerve supply), normal or disordered bowel habits, (i.e., fecal retention or diarrhea), and psychological causes. Furthermore, exclusion criteria are given. These are factors which all must be excluded for a diagnosis of functional FI, and are abnormal innervation caused by lesion(s) within the brain (e.g., dementia), spinal cord (at or below T12), or sacral nerve roots, or mixed lesions (e.g., multiple sclerosis), or as part of a generalized peripheral or autonomic neuropathy (e.g., due to diabetes), anal sphincter abnormalities associated with a multisystem disease (e.g., scleroderma), and structural or neurogenic abnormalities that are the major cause. There is no globally accepted definition, but fecal incontinence is generally defined as the recurrent inability to voluntarily control the passage of bowel contents through the anal canal and expel it at a socially acceptable location and time, occurring in individuals over the age of four. "Social continence" has been given various precise definitions for the purposes of research, however generally it refers to symptoms being controlled to an extent that is acceptable to the individual in question, with no significant effect on their life. There is no consensus about the best way to classify FI, and several methods are used. Symptoms can be directly or indirectly related to the loss of bowel control. The direct (primary) symptom is a lack of control over bowel contents which tends to worsen without treatment. Indirect (secondary) symptoms, which are the result of leakage, include pruritus ani (an intense itching sensation from the anus), perianal dermatitis (irritation and inflammation of the skin around the anus), and urinary tract infections. Due to embarrassment, people may only mention secondary symptoms rather than acknowledge incontinence. Any major underlying cause will produce additional signs and symptoms, such as protrusion of mucosa in external rectal prolapse. Symptoms of fecal leakage (FL) are similar, and may occur after defecation. There may be loss of small amounts of brown fluid and staining of the underwear. FI can be divided into those people who experience a defecation urge before leakage (urge incontinence), and those who experience no sensation before leakage (passive incontinence or soiling). Urge incontinence is characterized by a sudden need to defecate, with little time to reach a toilet. Urge and passive FI may be associated with weakness of the external anal sphincter (EAS) and internal anal sphincter (IAS) respectively. Urgency may also be associated with reduced rectal volume, reduced ability of the rectal walls to distend and accommodate stool, and increased rectal sensitivity. There is a continuous spectrum of different clinical presentations from incontinence of flatus (gas), through incontinence of mucus or liquid stool, to solids. The term anal incontinence often is used to describe flatus incontinence, however it is also used as a synonym for FI generally. It may occur together with incontinence of liquids or solids, or it may present in isolation. Flatus incontinence may be the first sign of FI. Once continence to flatus is lost, it is rarely restored. Anal incontinence may be equally disabling as the other types. Fecal leakage, fecal soiling and fecal seepage are minor degrees of FI, and describe incontinence of liquid stool, mucus, or very small amounts of solid stool. They cover a spectrum of increasing symptom severity (staining, soilage, seepage and accidents). Rarely, minor FI in adults may be described as encopresis. Fecal leakage is a related topic to rectal discharge, but this term does not necessarily imply any degree of incontinence. Discharge generally refers to conditions where there is pus or increased mucus production, or anatomical lesions that prevent the anal canal from closing fully, whereas fecal leakage generally concerns disorders of IAS function and functional evacuation disorders which cause a solid fecal mass to be retained in the rectum. Solid stool incontinence may be called complete (or major) incontinence, and anything less as partial (or minor) incontinence (i.e. incontinence of flatus (gas), liquid stool and/or mucus). In children over the age of four who have been toilet trained, a similar condition is generally termed encopresis (or soiling), which refers to the voluntary or involuntary loss of (usually soft or semi-liquid) stool. The term pseudoincontinence is used when there is FI in children who have anatomical defects (e.g. enlarged sigmoid colon or anal stenosis). Encopresis is a term that is usually applied when there are no such anatomical defects present. The ICD-10 classifies nonorganic encopresis under "behavioural and emotional disorders with onset usually occurring in childhood and adolescence" and organic causes of encopresis along with FI. FI can also be classified according to gender, since the cause in females may be different from males, for example it may develop following radical prostatectomy in males, whereas females may develop FI as an immediate or delayed consequence of damage whilst giving birth. Pelvic anatomy is also different according to gender, with a wider pelvic outlet in females. Several severity scales exist. The Cleveland Clinic (Wexner) fecal incontinence score takes into account five parameters that are scored on a scale from zero (absent) to four (daily) frequency of incontinence to gas, liquid, solid, of need to wear pad, and of lifestyle changes. The Park's incontinence score uses four categories: - 1 - those continent for solid and liquid stool and also for flatus. - 2 - those continent for solid and liquid stool but incontinent for flatus (with or without urgency). - 3 - those continent for solid stool but incontinent for liquid stool or flatus. - 4 - those incontinent to formed stool (complete incontinence). The fecal incontinence severity index is based on four types of leakage (gas, mucus, liquid stool, solid stool) and five frequencies (once to three times per month, once per week, twice per week, once per day, twice or more per day). Other severity scales include: AMS, Pescatori, Williams score, Kirwan, Miller score, Saint Mark's score and the Vaizey scale. FI may present with signs similar to rectal discharge (e.g. fistulae, proctitis or rectal prolapse), pseudoincontinence, encopresis (with no organic cause) and irritable bowel syndrome. \|Stool consistency\|\|Cause\|\|First line\|\|Second line\| \|Diarrhea\|\|Inflammatory\|\|Anti-inflammatory drugs\|\|Constipating drugs\| \|Solid\|\|Pelvic floor\|\|Biofeedback\|\|Sacral nerve stimulation\| \|Sphincter intact\|\|Sacral nerve stimulation\|\|Lavage\| \|Sphincter rupture\|\|Anal repair\|\|Sacral nerve stimulation/Neosphincter\| \|Rectal prolapse\|\|Rectopexy\|\|Perineal resection\| \|Soiling\|\|Keyhole defect\|\|Lavage\|\|PTQ implant\| FI is generally treatable with conservative management, surgery or both. The success of treatment depends upon the exact causes and how easily these are corrected. Treatment choice depends on the cause and severity of disease, and the motivation and general health of the person effected. Commonly, conservative measures are used together, and if appropriate surgery carried out. Treatments may be attempted until symptoms are satisfactorily controlled. A treatment algorithm based upon the cause has been proposed, including conservative, non-operative and surgical measures (neosphincter refers to either dynamic graciloplasty or artificial bowel sphincter, lavage refers to retrograde rectal irrigation). Conservative measures include dietary modification, drug treatment, retrograde anal irrigation, biofeedback retraining anal sphincter exercises. Incontinence products refer to devices such as anal plugs and perineal pads and garments such as diapers/nappies. Perineal pads are efficient and acceptable for only minor incontinence. If all other measures are ineffective removing the entire colon may be an option. Dietary modification may be important for successful management. Both diarrhea and constipation can contribute to different cases, so dietary advice must be tailored to address the underlying cause or it may be ineffective or counter productive. In persons with disease aggravated by diarrhea or those with rectal loading by soft stools, the following suggestions may be beneficial: increase dietary fiber; reduce wholegrain cereals/bread; reduce fruit and vegetables which contain natural laxative compounds (rhubarb, figs, prunes/plums); limit beans, pulses, cabbage and sprouts; reduce spices (especially chilli); reduce artificial sweeteners (e.g. sugar free chewing gum); reduce alcohol (especially stout, beer and ale); reduce lactose if there is some degree of lactase deficiency; and reduce caffeine. Caffeine lowers the resting tone of the anal canal and also causes diarrhea. Excessive doses of vitamin C, magnesium, phosphorus and/or calcium supplements may increase FI. Reducing olestra fat substitute, which can cause diarrhea, may also help. Pharmacological management may include anti-diarrheal/constipating agents and laxatives/stool bulking agents Stopping or substituting any previous medication that causes diarrhea may be helpful in some (see table). There is not good evidence for the use of any medications however. In people who have undergone gallbladder removal, the bile acid sequestrant cholestyramine may help minor degrees of FI. Bulking agents also absorb water, so may be helpful for those with diarrhea. A common side effect is bloating and flatulence. Topical agents to treat and prevent dermatitis may also be used, such as topical antifungals when there is evidence of perianal candidiasis or occasionally mild topical anti-inflammatory medication. Prevention of secondary lesions is carried out by perineal cleansing, moisturization, and use of a skin protectant. Evacuation aids (suppositories or enemas) e.g. glycerine or bisacodyl suppositories may be prescribed. People may have poor resting tone of the anal canal, and consequently may not be able to retain an enema, in which case transanal irrigation (retrograde anal irrigation) may be a better option, as this equipment utilizes an inflatable catheter to prevent loss of the irrigation tip and to provide a water tight seal during irrigation. A volume of lukewarm water is gently pumped into the colon via the anus. People can be taught how to perform this treatment in their own homes, but it does require special equipment. If the irrigation is efficient, stool will not reach the rectum again for up to 48 hours. By regularly emptying the bowel using transanal irrigation, controlled bowel function is often re-established to a high degree in patients with bowel incontinence and/or constipation. This enables control over the time and place of evacuation and development of a consistent bowel routine. However, persistent leaking of residual irrigation fluid during the day may occur and make this option unhelpful, particularly in persons with obstructed defecation syndrome who may have incomplete evacuation of any rectal contents. Consequently, the best time to carry out the irrigation is typically in the evening, allowing any residual liquid to be passed the next morning before leaving the home. Complications such as electrolyte imbalance and perforation are rare. The effect of transanal irrigation varies considerably. Some individuals experience complete control of incontinence, and other report little or no benefit. It has been suggested that if appropriate, people be offered home retrograde anal irrigation. Biofeedback (the use equipment to record or amplify and then feed back activities of the body) is a commonly used and researched treatment, but the benefits are uncertain. Biofeedback therapy varies in the way it is delivered, but it is unknown if one type has benefits over another. The role of pelvic floor exercises and anal sphincter exercises in FI is poorly determined. While there may be some benefit they appear less useful than implanted sacral nerve stimulators. These exercises aim to increase the strength of the pelvic floor muscles (mainly levator ani). The anal sphincters are not technically part of the pelvic floor muscle group, but the EAS is a voluntary, striated muscle which therefore can be strengthened in a similar manner. It has not been established whether pelvic floor exercises can be distinguished from anal sphincter exercises in practice by the people doing them. This kind of exercise is more commonly used to treat urinary incontinence, for which there is a sound evidence base for effectiveness. More rarely are they used in FI. The effect of anal sphincter exercises are variously stated as an increase in the strength, speed or endurance of voluntary contraction (EAS). Electrical stimulation can also be applied to the anal sphincters and pelvic floor muscles, inducing muscle contraction without traditional exercises (similar to transcutaneous electrical nerve stimulation, TENS). The evidence supporting its use is limited, and any benefit is tentative. In light of the above, intra-anal electrical stimulation (using an anal probe as electrode) appears to be more efficacious than intra-vaginal (using a vaginal probe as electrode). Rarely, skin reactions may occur where the electrodes are placed, but these issues typically resolve when the stimulation is stopped. Surgically implanted sacral nerve stimulation may be more effective than exercises, and electrical stimulation and biofeedback may be more effective than exercises or electrical stimulation by themselves. TENS is also sometimes used to treat FI by transcutaneous tibial nerve stimulation. In a minority of people, anal plugs may be useful for either standalone therapy or in concert with other treatments. Anal plugs (sometimes termed tampons) aim to block involuntary loss of fecal material, and they vary in design and composition. Polyurethane plugs were reported to perform better than those made of polyvinyl-alcohol. Plugs are less likely to help those with frequent bowel movements, and many find them difficult to tolerate. In women, a device that functions as an inflatable balloon in the vagina, has been approved for use in the United States. Surgery may be carried out if conservative measures alone are not sufficient to control incontinence. There are many surgical options, and their relative effectiveness is debated due to a lack of good quality evidence. The optimal treatment regime may be a both surgical and non-surgical treatments. The surgical options can be considered in four categories: restoration and improvement of residual sphincter function (sphincteroplasty, sacral nerve stimulation, tibial nerve stimulation, correction of anorectal deformity), replacement / imitation of the sphincter or its function (anal encirclement, SECCA procedure, non-dynamic graciloplasty, perianal injectable bulking agents), dynamic sphincter replacement (artificial bowel sphincter, dynamic graciloplasty), antegrade continence enema (Malone procedure), and finally fecal diversion (e.g. colostomy). A surgical treatment algorithm has been proposed. Isolated sphincter defects (IAS/EAS) may be initially treated with sphincteroplasty and if this fails, the person can be assessed for sacral nerve stimulation. Functional deficits of the EAS and/or IAS (i.e. where there is no structural defect, or only limited EAS structural defect, or with neurogenic incontinence) may be assessed for sacral nerve stimulation. If this fails, neosphincter with either dynamic graciloplasty or artificial anal sphincter may be indicated. Substantial muscular and/or neural defects may be treated with neosphincter initially. FI is thought to be very common, but much under-reported due to embarrassment. One study reported a prevalence of 2.2% in the general population. It affects people of all ages, but is more common in older adults (but it should not be considered a normal part of aging). Females are more likely to develop it than males (63% of those with FI over 30 may be female). In 2014, the National Center for Health Statistics reported that one out of every six seniors in the U.S. who lived in their own home or apartment had FI. Men and women were equally affected. 45–50% of people with FI have severe physical and/or mental disabilities. Risk factors include age, female gender, urinary incontinence, history of vaginal delivery (non-Caesarean section childbirth), obesity, prior anorectal surgery, poor general health and physical limitations. Combined urinary and fecal incontinence is sometimes termed double incontinence, and it is more likely to be present in those with urinary incontinence. Traditionally, FI was thought to be an insignificant complication of surgery, but it is now known that a variety of different procedures are associated with this possible complication, and sometimes at high levels. Examples are midline internal sphincterotomy (8% risk), lateral internal sphincterotomy, fistulectomy, fistulotomy (18-52%), hemorrhoidectomy (33%), ileo-anal reservoir reconstruction, lower anterior resection, total abdominal colectomy, ureterosigmoidostomy, and anal dilation (Lord's procedure, 0-50%). Some authors consider obstetric trauma to be the most common cause. While the first mention of urinary incontinence occurs in 1500 BC in the Ebers Papyrus, the first mention of FI in a medical context is unknown. For many centuries, colonic irrigation was the only treatment available. Stoma creation was described in 1776, FI associated with rectal prolapse in 1873 and anterior sphincter repair in 1875. During the mid 20th Century, several operations were developed for instances where the sphincters were intact but weakened. Muscle transpositions using the gluteus maximus or the gracilis were devised, but did not become used widely until later. End-to-end sphincteroplasty is shown to have a high failure rate in 1940. In 1971 Parks and McPartlin first describe an overlapping sphincteroplasty procedure. Biofeedback is first introduced in 1974. In 1975, Parks describes post anal repair, a technique to reinforce the pelvic floor and EAS to treat idiopathic cases. Endoanal ultrasound is invented in 1991, which starts to demonstrate the high number of occult sphincter tears following vaginal deliveries. In 1994, the use of an endoanal coil during pelvic MRI shows greater detail of the anal canal than previously. During the last 20 years, dynamic graciliplasty, sacral nerve stimulation, injectable perianal bulking agents and radiofrequency ablation have been devised, mainly due to the relatively poor success rates and high morbidity associated with the earlier procedures. Society and culture Persons with this symptom are frequently ridiculed and ostracized in public. It has been described as one of the most psychologically and socially debilitating conditions in an otherwise healthy individual. In older people, it is one of the most common reasons for admission into a care home. Persons who develop FI earlier in life are less likely to marry and obtain employment. Often, people will go to great lengths to keep their condition secret. It has been termed "the silent affliction" since many do not discuss the problem with their close family, employers or clinicians. They may be subject to gossip, hostility, and other forms of social exclusion. The economic cost has not received much attention. In the Netherlands, outpatients were reported to have total costs of €2169 annually, and over half of this was productivity loss in work. In the USA, the average lifetime cost (treatment and follow-up) was $17,166 per person in 1996. The average hospital charges for sphincteroplasty was $8555 per procedure. Overall, in the USA, the total charges associated with surgery increased from $34 million in 1998 to $57.5 million in 2003. Sacral nerve stimulation, dynamic graciloplasty and colostomy were all shown to be cost effective. 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"Barriers on Diagnosis and Treatment; Impact of Fecal and Urinary Incontinence on Health Consumers – Barriers on Diagnosis and Treatment – A Patient Perspective". International Foundation for Functional Gastrointestinal Disorders (IFFGD). Retrieved 1 January 2013. - Ranganath, Sonia; Tanaz R Ferzandi. "Fecal Incontinence". WebMD LLC. Retrieved 1 January 2013. - Bliss, DZ; Norton, C (September 2010). "Conservative management of fecal incontinence". The American journal of nursing. 110 (9): 30–8; quiz 39–40. doi:10.1097/01.NAJ.0000388262.72298.f5. PMID 20736708. - Paul Abrams et al., eds. (2009). "Economics of urinary and faecal incontinence, and prolapse". Incontinence : 4th International Consultation on Incontinence, Paris, July 5-8, 2008 (4th ed.). [Paris]: Health Publications. p. 1685. ISBN 0-9546956-8-2. - Wilson, Scott. "W.T.F. Japan: Top 5 most offensive Japanese swear words 【Weird Top Five】". SoraNews24. Retrieved 12 May 2017. - Koch, Kenneth L (1 January 2012). "Tissue engineering for neuromuscular disorders of the gastrointestinal tract". World Journal of Gastroenterology. 18 (47): 6918–25. doi:10.3748/wjg.v18.i47.6918. PMC . PMID 23322989.	2	36	8	0	0	5	0.96056	13	11,313
... Other Visiting Your Doctor Evaluation + Tests Autonomic Testing Nerve/Skin/Muscle Biopsy Computerized Axial Tomography Scan (CAT) Electrodiagnostic Testing Lumbar Puncture Imaging Quantitative Sensory Testing (QST) Peripheral Neuropathy ... ... sensation or freezing pain Sharp, jabbing, shooting, or electric-like pain Extreme sensitivity to touch Difficulty sleeping ... damaged. There are three types of peripheral nerves: motor, sensory and autonomic. Some neuropathies affect all three ... Watson, James C; Dyck, P James B Peripheral neuropathy is one of the most prevalent neurologic conditions encountered by physicians of all specialties. Physicians are faced with 3 distinct challenges in caring for patients with peripheral neuropathy: (1) how to efficiently and effectively screen (in less than 2 minutes) an asymptomatic patient for peripheral neuropathy when they have a disorder in which peripheral neuropathy is highly prevalent (eg, diabetes mellitus), (2) how to clinically stratify patients presenting with symptoms of neuropathy to determine who would benefit from specialty consultation and what testing is appropriate for those who do not need consultation, and (3) how to treat the symptoms of painful peripheral neuropathy. In this concise review, we address these 3 common clinical scenarios. Easily defined clinical patterns of involvement are used to identify patients in need of neurologic consultation, the yield of laboratory and other diagnostic testing is reviewed for the evaluation of length-dependent, sensorimotor peripheral neuropathies (the most common form of neuropathy), and an algorithmic approach with dosing recommendations is provided for the treatment of neuropathic pain associated with peripheral neuropathy. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved. Hanewinckel, R; Ikram, M A; Van Doorn, P A Peripheral neuropathies are diseases of the peripheral nervous system that can be divided into mononeuropathies, multifocal neuropathies, and polyneuropathies. Symptoms usually include numbness and paresthesia. These symptoms are often accompanied by weakness and can be painful. Polyneuropathies can be divided into axonal and demyelinating forms, which is important for diagnostic reasons. Most peripheral neuropathies develop over months or years, but some are rapidly progressive. Some patients only suffer from mild, unilateral, slowly progressive tingling in the fingers due to median nerve compression in the wrist (carpal tunnel syndrome), while other patients can be tetraplegic, with respiratory insufficiency within 1-2 days due to Guillain-Barré syndrome. Carpal tunnel syndrome, with a prevalence of 5% and incidence of 1-2 per 1000 person-years, is the most common mononeuropathy. Population-based data for chronic polyneuropathy are relatively scarce. Prevalence is estimated at 1% and increases to 7% in persons over 65 years of age. Incidence is approximately 1 per 1000 person-years. Immune-mediated polyneuropathies like Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy are rare diseases, with an annual incidence of approximately 1-2 and 0.2-0.5 per 100 000 persons respectively. Most peripheral neuropathies are more prevalent in older adults and in men, except for carpal tunnel syndrome, which is more common in women. Diabetes is a common cause of peripheral neuropathy and is associated with both mono- and polyneuropathies. Among the group of chronic polyneuropathies, in about 20-25% no direct cause can be found. These are slowly progressive axonal polyneuropathies. © 2016 Elsevier B.V. All rights reserved. Sim, Mi Kyung; Yoon, Jisun; Park, Dae Hwan; Kim, Yong-Gil Objective To assess the prevalence of peripheral neuropathy in patients with rheumatoid arthritis (RA) having neuropathic symptoms, and to investigate the relationship between electrophysiological findings of peripheral neuropathy and clinical findings of RA. Methods Patients with a clinical diagnosis of RA and who had tingling or burning sensation in any extremity were electrophysiologically examined for evidence of peripheral neuropathy. Study parameters, including age, gender, laboratory parameters, duration of RA, and medication, were recorded. The symptoms and signs of neuropathy were quantified with the neuropathy symptom score, and the functional statuses of these patients were assessed. Results Out of a total of 30 RA patients, 10 (33%) had peripheral neuropathy: 2 had bilateral carpal tunnel syndrome (CTS), 5 had unilateral CTS, 1 had sensory polyneuropathy, and 2 had motor-sensory polyneuropathy. The mean ages of the patients with and without peripheral neuropathy were 69.4 and 56.5 years, respectively (p<0.05). A significant relationship was found between peripheral neuropathy and anti-cyclic citrullinated peptide (anti-CCP) antibody. However, no relationship was found between peripheral neuropathy and the type of medication, RA duration, the patients' functional status, neuropathic symptoms, erythrocyte sedimentation rate, and C-reactive protein values. Conclusion Neuropathic symptoms are common in RA patients, and it is difficult to distinguish peripheral neuropathy symptoms from those of arthritis. Patients with RA, particularly elderly patients and anti-CCP antibody positive patients who complain of neuropathic symptoms should undergo electrophysiological examination. PMID:24855620 Sim, Mi Kyung; Kim, Dae-Yul; Yoon, Jisun; Park, Dae Hwan; Kim, Yong-Gil To assess the prevalence of peripheral neuropathy in patients with rheumatoid arthritis (RA) having neuropathic symptoms, and to investigate the relationship between electrophysiological findings of peripheral neuropathy and clinical findings of RA. Patients with a clinical diagnosis of RA and who had tingling or burning sensation in any extremity were electrophysiologically examined for evidence of peripheral neuropathy. Study parameters, including age, gender, laboratory parameters, duration of RA, and medication, were recorded. The symptoms and signs of neuropathy were quantified with the neuropathy symptom score, and the functional statuses of these patients were assessed. Out of a total of 30 RA patients, 10 (33%) had peripheral neuropathy: 2 had bilateral carpal tunnel syndrome (CTS), 5 had unilateral CTS, 1 had sensory polyneuropathy, and 2 had motor-sensory polyneuropathy. The mean ages of the patients with and without peripheral neuropathy were 69.4 and 56.5 years, respectively (p<0.05). A significant relationship was found between peripheral neuropathy and anti-cyclic citrullinated peptide (anti-CCP) antibody. However, no relationship was found between peripheral neuropathy and the type of medication, RA duration, the patients' functional status, neuropathic symptoms, erythrocyte sedimentation rate, and C-reactive protein values. Neuropathic symptoms are common in RA patients, and it is difficult to distinguish peripheral neuropathy symptoms from those of arthritis. Patients with RA, particularly elderly patients and anti-CCP antibody positive patients who complain of neuropathic symptoms should undergo electrophysiological examination. Gewandter, Jennifer S; Burke, Laurie; Cavaletti, Guido; Dworkin, Robert H; Gibbons, Christopher; Gover, Tony D; Herrmann, David N; Mcarthur, Justin C; McDermott, Michael P; Rappaport, Bob A; Reeve, Bryce B; Russell, James W; Smith, A Gordon; Smith, Shannon M; Turk, Dennis C; Vinik, Aaron I; Freeman, Roy No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes are central to evaluating neuropathy symptoms, they can be difficult to assess accurately. The inability to identify efficacious treatments for peripheral neuropathies could be due to invalid or inadequate outcome measures. This systematic review examined the content validity of symptom-based measures of diabetic peripheral neuropathy, HIV neuropathy, and chemotherapy-induced peripheral neuropathy. Use of all FDA-recommended methods to establish content validity was only reported for 2 of 18 measures. Multiple sensory and motor symptoms were included in measures for all 3 conditions; these included numbness, tingling, pain, allodynia, difficulty walking, and cramping. Autonomic symptoms were less frequently included. Given significant overlap in symptoms between neuropathy etiologies, a measure with content validity for multiple neuropathies with supplemental disease-specific modules could be of great value in the development of disease-modifying treatments for peripheral neuropathies. Muscle Nerve 55: 366-372, 2017. © 2016 Wiley Periodicals, Inc. GEWANDTER, JENNIFER S.; BURKE, LAURIE; CAVALETTI, GUIDO; DWORKIN, ROBERT H.; GIBBONS, CHRISTOPHER; GOVER, TONY D.; HERRMANN, DAVID N.; MCARTHUR, JUSTIN C.; MCDERMOTT, MICHAEL P.; RAPPAPORT, BOB A.; REEVE, BRYCE B.; RUSSELL, JAMES W.; SMITH, A. GORDON; SMITH, SHANNON M.; TURK, DENNIS C.; VINIK, AARON I.; FREEMAN, ROY Introduction No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes are central to evaluating neuropathy symptoms, they can be difficult to assess accurately. The inability to identify efficacious treatments for peripheral neuropathies could be due to invalid or inadequate outcome measures. Methods This systematic review examined the content validity of symptom-based measures of diabetic peripheral neuropathy, HIV neuropathy, and chemotherapy-induced peripheral neuropathy. Results Use of all FDA-recommended methods to establish content validity was only reported for 2 of 18 measures. Multiple sensory and motor symptoms were included in measures for all 3 conditions; these included numbness, tingling, pain, allodynia, difficulty walking, and cramping. Autonomic symptoms were less frequently included. Conclusions Given significant overlap in symptoms between neuropathy etiologies, a measure with content validity for multiple neuropathies with supplemental disease-specific modules could be of great value in the development of disease-modifying treatments for peripheral neuropathies. PMID:27447116 ... and resolve slowly as damaged nerves heal. In chronic forms, symptoms begin subtly and progress slowly. Some ... the same for many months or years. Some chronic neuropathies worsen over time, but very few forms ... Evliyaoglu, Ferhat; Karadag, Remzi; Burakgazi, Ahmet Z Ocular movements and coordination require complex and integrated functions of somatic and autonomic nervous systems. Neurological disorders affecting these nervous systems may cause ocular dysfunction involving extraocular muscles and pupils. In this article, the prevalence, clinical presentations, and management of ocular neuropathy related to certain peripheral neuropathies, including diabetic neuropathy, Guillain-Barré syndrome (GBS), chronic inflammatory neuropathies, human immunodeficiency virus (HIV)-associated neuropathy, and hereditary neuropathies, are examined in detail. Copyright © 2012 Wiley Periodicals, Inc. Nicholas, P K; Kemppainen, J K; Canaval, G E; Corless, I B; Sefcik, E F; Nokes, K M; Bain, C A; Kirksey, K M; Eller, L Sanzero; Dole, P J; Hamilton, M J; Coleman, C L; Holzemer, W L; Reynolds, N R; Portillo, C J; Bunch, E H; Wantland, D J; Voss, J; Phillips, R; Tsai, Y-F; Mendez, M Rivero; Lindgren, T G; Davis, S M; Gallagher, D M Peripheral neuropathy is the most common neurological complication in HIV and is often associated with antiretroviral therapy. As part of a larger study on self-care for symptoms in HIV disease, this study analyzed the prevalence and characteristics of peripheral neuropathy in HIV disease, sociodemographic and disease-related correlates and self-care strategies. A convenience sample of 1,217 respondents was recruited from data collection sites in several US cities, Puerto Rico, Colombia and Taiwan. Results of the study indicated that respondents with peripheral neuropathy (n=450) identified 20 self-care behaviors including complementary therapies, use of medications, exercise and rest and/or elevation of extremities. Ratings of frequency and effectiveness were also included. An activities checklist summarized into five categories of self-care behaviors including activities/thoughts, exercise, medications, complementary therapies and substance was used to determine self-care behaviors. Taking a hot bath was the most frequent strategy used by those with peripheral neuropathy (n=292) and received the highest overall rating of effectiveness of any self-management strategies included in this study at 8.1 (scale 1-10). Other self-care strategies to manage this symptom included: staying off the feet (n=258), rubbing the feet with cream (n=177), elevating the feet (n=236), walking (n=262), prescribed anti-epileptic agent (n=80), prescribed analgesics (n=84), over-the-counter medications (n=123), vitamin B (n=122), calcium supplements (n=72), magnesium (n=48), massage (n=156), acupuncture (n=43), reflexology (n=23) and meditation (n=80). Several behaviors that are often deemed unhealthy were included among the strategies reported to alleviate peripheral neuropathy including use of marijuana (n=67), cigarette smoking (n=139), drinking alcohol (n=81) and street drugs (n=30). Majumder, A; Chatterjee, S; Maji, D Peripheral neuropathy is common complication of diabetes. The prevalence of peripheral neuropathy among diabetic patients on the basis of loss of vibration sensation had been studied. Detailed clinical history of each patient including age, gender, duration of diabetes, foot ulcer and biothesiometry was recorded in 211 diabetic patients between 20 and 80 years of age. It was observed that all patients under 30 years age (n = 8) felt vibration below 15 volts (no risk zone); 77% (24 out of 31) of the patients in the age group of 30-39 years were in the no risk zone, and 23% (n = 7) had mild peripheral neuropathy. Sixty per cent of the patients between 40 and 50 years (n = 44) were in the no risk zone, while 32% (n = 24) had mild peripheral neuropathy, 5% (n = 4) had moderate neuropathy and 3% (n = 2) had severe peripheral neuropathy. Amongst patients above 50 years of age, 31% (n = 31) were in no risk zone, 34% (n = 34) had mild peripheral neuropathy, 22% (n = 20) had moderate peripheral neuropathy and 13% (n = 13) had severe peripheral neuropathy. Of the patients with diabetes for less than 5 years, 58% had no neuropathy, and only 3% had severe neuropathy. Of the patients with diabetes for 5 to 15 years, 50% had no neuropathy, 30% had mild, and 10% had severe peripheral neuropathy. When patients with diabetes for over 15 years were studied, only 6% had no neuropathy and 19% had severe peripheral neuropathy. The study re-establishes that the severity of peripheral neuropathy increases with age and vibration perception decreses progressively with increased duration of diabetes. Vibration perception threshold testing helps to identify the high risk subjects who require special counselling and education to protect their feet. Nicholas, Patrice K; Voss, Joachim; Wantland, Dean; Lindgren, Teri; Huang, Emily; Holzemer, William L; Cuca, Yvette; Moezzi, Shahnaz; Portillo, Carmen; Willard, Suzanne; Arudo, John; Kirksey, Kenn; Corless, Inge B; Rosa, María E; Robinson, Linda; Hamilton, Mary J; Sefcik, Elizabeth; Human, Sarie; Rivero-Mendez, Marta; Maryland, Mary; Nokes, Kathleen M; Eller, Lucille; Kemppainen, Jeanne; Dawson-Rose, Carol; Brion, John M; Bunch, Elli H; Shannon, Maureen; Nicholas, Thomas P; Viamonte-Ros, Ana; Bain, Catherine A As part of a larger randomized controlled trial examining the efficacy of an HIV/AIDS symptom management manual (n = 775), this study examined the prevalence of peripheral neuropathy in HIV-infected individuals at 12 sites in the USA, Puerto Rico, and Africa. Neuropathy was reported by 44% of the sample; however, only 29.4% reported initiating self-care behaviors to address the neuropathy symptoms. Antiretroviral therapy was found to increase the frequency of neuropathy symptoms, with an increased mean intensity of 28%. A principal axis factor analysis with Promax rotation was used to assess the relationships in the frequency of use of the 18 self-care activities for neuropathy, revealing three distinct factors: (i) an interactive self-care factor; (ii) a complementary medicine factor; and (iii) a third factor consisting of the negative health items of smoking, alcohol, and street drugs. The study's results suggest that peripheral neuropathy is a common symptom and the presence of neuropathy is associated with self-care behaviors to ameliorate HIV symptoms. The implications for nursing practice include the assessment and evaluation of nursing interventions related to management strategies for neuropathy. ... ZIP code here Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset ... percent disabling by VA's rating regulations. About peripheral neuropathy Peripheral neuropathy is a condition of the peripheral ... Kolb, Noah A; Smith, A Gordon; Singleton, J Robinson; Beck, Susan L; Stoddard, Gregory J; Brown, Summer; Mooney, Kathi Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of neurotoxic chemotherapy resulting in pain, sensory loss, and decreased quality of life. Few studies have prospectively examined the relationship between sensory neuropathy symptoms, falls, and fall-related injuries for patients receiving neurotoxic chemotherapy. To determine the association between the symptoms of CIPN and the risk of falls for patients receiving neurotoxic chemotherapy. In this secondary analysis of a prospective study, 116 patients with breast, ovarian, or lung cancer who were beginning neurotoxic chemotherapy with a taxane or platinum agent were recruited from oncology clinics. These patients would call a novel automated telephone system daily for 1 full course of chemotherapy. The telephone system (SymptomCare@Home) used a series of relevant CIPN questions to track symptoms on a 0 to 10 ordinal scale and contained a questionnaire about falls. Those reporting a numbness and tingling severity score of 3 or greater for at least 10 days were considered to have significant CIPN symptoms and were compared with those patients who did not. Data analysis was performed in November 2015. Chemotherapy with a neurotoxic taxane or platinum agent. Patient-reported falls or near falls and fall-related injuries. The hypothesis was generated after data collection but prior to data analysis. Of the 116 patients who started neurotoxic chemotherapy (mean [SD] age was 55.5 [11.9] years, and 109 [94.0%] were female), 32 met the predetermined criteria for CIPN symptoms. The mean duration of follow-up was 62 days, with 51 telephone calls completed per participant. Seventy-four falls or near falls were reported. The participants with CIPN symptoms were nearly 3 times more likely to report a fall or near fall than the participants without CIPN symptoms (hazard ratio, 2.67 [95% CI, 1.62-4.41]; P < .001). The participants with CIPN symptoms were more likely than the participants without Assal, J.P.; Liniger, C. The authors present results and experience in sixteen specific disciplines related to the study of nerve physiopathology, diagnosis and treatment. Twenty-two different peripheral neuropathies are presented, and different models related to health care strategies are discussed. The authors report on Inflammatory and autoimmune neuropathies and Genetic neuropathies. Saporta, Mario A; Shy, Michael E Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurologic or multisystem syndrome. Because of the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. This article reviews the biology of the inherited peripheral neuropathies, delineates major phenotypic features of the CMT subtypes, and suggest strategies for focusing genetic testing. Copyright © 2013 Elsevier Inc. All rights reserved. Saporta, Mario A.; Shy, Michael E. SYNOPSIS Charcot Marie Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurological or multisystem syndrome. Due to the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. Here, we review the biology of the inherited peripheral neuropathies, delineate major phenotypic features of the CMT subtypes and suggest strategies for focusing genetic testing. PMID:23642725 Miranda-Massari, Jorge R.; Gonzalez, Michael J.; Jimenez, Francisco J.; Allende-Vigo, Myriam Z.; Duconge, Jorge Current Clinical Management Guidelines of Diabetic Peripheral Neuropathy (DPN) are based on adequate glucose control and symptomatic pain relief. However, meticulous glycemic control could delay the onset or slow the progression of diabetic neuropathy in patients with DM type 2, but it does not completely prevent the progression of the disease. Complications of DPN as it continues its natural course, produce increasing pain and discomfort, loss of sensation, ulcers, infections, amputations and even death. In addition to the increased suffering, disability and loss of productivity, there is a very significant economic impact related to the treatment of DPN and its complications. In USA alone, it has been estimated that there are more than 5,000,000 patients suffering from DPN and the total annual cost of treating the disease and its complications is over $10,000 million dollars. In order to be able to reduce complications of DPN, it is crucial to improve or correct the metabolic conditions that lead to the pathology present in this condition. Pathophysiologic mechanisms implicated in diabetic neuropathy include: increased polyol pathway with accumulation of sorbitol and reduced Na+/K+-ATPase activity, microvascular damage and hypoxia due to nitric oxide deficit and increased oxygen free radical activity. Moreover, there is a decrease in glutathione and increase in homocysteine. Clinical trials in the last two decades have demonstrated that the use of specific nutrients can correct some of these metabolic derangements, improving symptom control and providing further benefits such as improved sensorium, blood flow and nerve regeneration. We will discuss the evidence on lipoic acid, acetyi-L-carnitine, benfotiamine and the combination of active B vitamins L-methylfolate, methylcobalamin and piridoxal-6-phosphate. In addition, we discuss the role of metforrnin, an important drug in the management of diabetes, and the presence of specific polymorphic genes, in the risk Hallett, M; Tandon, D; Berardelli, A There are three general approaches to treatment of peripheral neuropathy. First, an attempt should be made to reverse the pathophysiological process if its nature can be elucidated. Second, nerve metabolism can be stimulated and regeneration encouraged. Third, even if the neuropathy itself cannot be improved, symptomatic therapy can be employed. This review outlines the options available for each approach. PMID:3003254 Winters-Stone, Kerri M; Horak, Fay; Jacobs, Peter G; Trubowitz, Phoebe; Dieckmann, Nathan F; Stoyles, Sydnee; Faithfull, Sara Purpose Chemotherapy-induced peripheral neuropathy (CIPN) may persist after treatment ends and may lead to functional decline and falls. This study compared objective and self-report measures of physical function, gait patterns, and falls between women cancer survivors with and without symptoms of CIPN to identify targets for functional rehabilitation. Methods A secondary data analysis of 512 women cancer survivors (age, 62 ± 6 years; time since diagnosis, 5.8 ± 4.1 years) categorized and compared women self-reporting symptoms of CIPN (CIPN+) with asymptomatic women (CIPN-) on the following: maximal leg strength, timed chair stand, physical function battery, gait characteristics (speed; step number, rate, and length; base of support), self-report physical function and disability, and falls in the past year. Results After an average of 6 years after treatment, 47% of women still reported symptoms of CIPN. CIPN+ had significantly worse self-report and objectively measured function than did CIPN-, with the exception of maximal leg strength and base of support during a usual walk. Gait was slower among CIPN+, with those women taking significantly more, but slower and shorter, steps than did CIPN- (all P < .05). CIPN+ reported significantly more disability and 1.8 times the risk of falls compared with CIPN- ( P < .0001). Increasing symptom severity was linearly associated with worsening function, increasing disability, and higher fall risk (all P < .05). Conclusion This work makes a significant contribution toward understanding the functional impact of CIPN symptoms on cancer survivors. Remarkably, 47% of women in our sample had CIPN symptoms many years after treatment, together with worse function, greater disability, and more falls. CIPN must be assessed earlier in the clinical pathway, and strategies to limit symptom progression and to improve function must be included in clinical and survivorship care plans. Brock, C; Graversen, C; Frøkjaer, J B; Søfteland, E; Valeriani, M; Drewes, A M Long-term diabetes mellitus (DM) has been associated with neuronal changes in the enteric, peripheral and/or central nervous system. Moreover, abnormal visceral sensation and gastrointestinal (GI) symptoms are seen in up to 75% of patients. To explore the role of diabetic autonomic neuropathy (DAN) in patients with long-standing DM, we investigated psychophysical responses and neuronal activity recorded as evoked brain potentials and dipolar source modelling. Fifteen healthy volunteers and 14 type-1 DM patients with DAN were assessed with a symptom score index characterizing upper GI abnormalities. Multichannel (62) electroencephalography was recorded during painful electrical stimulation of the lower oesophagus. Brain activity to painful stimulations was modelled using Brain Electrical Source Analysis (besa). Diabetic patients had higher stimulus intensities to evoke painful sensation (p ≤ 0.001), longer latencies of N2 and P2 components (both p ≤ 0.001), and lower amplitudes of P1-N2 and N2-P2 complexes (p ≤ 0.001; p = 0.02). Inverse modelling of brain sources showed deeper bilateral insular dipolar source localization (p = 0.002). Symptom score index was negatively correlated with the depth of insular activity (p = 0.004) and positively correlated with insular dipole strength (p = 0.03). DM patients show peripheral and central neuroplastic changes. Moreover, the role of abnormal insular processing may explain the appearance and persistence of GI symptoms related to DAN. This enhanced understanding of DAN may have future clinical and therapeutical implications. © 2012 European Federation of International Association for the Study of Pain Chapters. Shy, Michael E Mutations in genes expressed in Schwann cells and the axons they ensheathe cause the hereditary motor and sensory neuropathies, also known as Charcot-Marie-Tooth disease (CMT). More than 40 different genes have been shown to cause inherited neuropathies; chromosomal localizations of many other distinct inherited neuropathies have been mapped, and new genetic causes for inherited neuropathies continue to be discovered. How to keep track of all of these disorders, when to pursue genetic testing, and what tests to order for specific patients are difficult challenges for any neurologist. This review addresses these issues and provides illustrative cases to help in dealing with them. CMT serves as a living system to identify molecules necessary for normal peripheral nervous system (PNS) function. Understanding how these various molecules interact will provide a better understanding of the pathogenesis of peripheral neuropathies in general as well as other neurodegenerative disorders involving the PNS. Léger, Jean-Marc; Guimarães-Costa, Raquel; Muntean, Cristina Immunotherapy has been investigated in a small subset of peripheral neuropathies, including an acute one, Guillain-Barré syndrome, and 3 chronic forms: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and neuropathy associated with IgM anti-myelin-associated glycoprotein. Several experimental studies and clinical data are strongly suggestive of an immune-mediated pathogenesis. Either cell-mediated mechanisms or antibody responses to Schwann cell, compact myelin, or nodal antigens are considered to act together in an aberrant immune response to cause damage to peripheral nerves. Immunomodulatory treatments used in these neuropathies aim to act at various steps of this pathogenic process. However, there are many phenotypic variants and, consequently, there is a significant difference in the response to immunotherapy between these neuropathies, as well as a need to improve our knowledge and long-term management of chronic forms. Misra, Usha Kant; Kalita, Jayantee; Nair, Pradeep P. Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx) tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG). EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block) and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG). Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF) examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them. PMID:19893645 Burakgazi, Ahmet Z; AlMahameed, Soufian Cardiac autonomic neuropathy (CAN) is the least recognized and understood complication of peripheral neuropathy. However, because of its potential adverse effects including sudden death, CAN is one of the most important forms of autonomic neuropathies. CAN presents with different clinical manifestations including postural hypotension, exercise intolerance, fluctuation of blood pressure and heart rate, arrhythmia, and increased risk of myocardial infarction. In this article, the prevalence, clinical presentations, and management of cardiac involvement in certain peripheral neuropathies, including diabetic neuropathy, Guillain-Barré syndrome, chronic inflammatory polyneuropathy, human immunodeficiency virus-associated neuropathy, hereditary neuropathies, and amyloid neuropathy are examined in detail. Diagnosing a peripheral neuropathy is sometimes challenging, as the causes are diverse and the clinical pictures heterogeneous. Overall, diagnosing a patient with peripheral neuropathy will require some knowledge in almost every field of medicine. Therefore, it appears crucial to adopt a diagnostic strategy that is based on solid clinical and neurophysiological grounds. The present paper describes a three-step diagnostic strategy: (1) to delineate a clinico-pathologic entity from clinical and electrodiagnostic findings; (2) to propose a list of plausible causes based on step one, history and clinical context; (3) to use appropriate workup in order to determine the cause or mechanism of the neuropathy. The three steps of this diagnostic strategy necessitate a high level of expertise and interaction between physicians is highly desirable. Finally, an aggressive course and a severe impairment should lead to relentlessly look for a curable cause. Fehrenbacher, Jill C Chemotherapy-induced peripheral neuropathy (CIPN) is common in patients receiving anticancer treatment and can affect survivability and long-term quality of life of the patient following treatment. The symptoms of CIPN primarily include abnormal sensory discrimination of touch, vibration, thermal information, and pain. There is currently a paucity of pharmacological agents to prevent or treat CIPN. The lack of efficacious therapeutics is due, at least in part, to an incomplete understanding of the mechanisms by which chemotherapies alter the sensitivity of sensory neurons. Although the clinical presentation of CIPN can be similar with the various classes of chemotherapeutic agents, there are subtle differences, suggesting that each class of drugs might induce neuropathy via different mechanisms. Multiple mechanisms have been proposed to underlie the development and maintenance of neuropathy; however, most pharmacological agents generated from preclinical experiments have failed to alleviate the symptoms of CIPN in the clinic. Further research is necessary to identify the specific mechanisms by which each class of chemotherapeutics induces neuropathy. Jayabalan, Bhavani; Low, Lian Leng Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. Copyright © Singapore Medical Association. Tu, Yiji; Lineaweaver, William C; Zheng, Xianyou; Chen, Zenggan; Mullins, Fred; Zhang, Feng Peripheral neuropathy is the most frequent disabling neuromuscular complication of burns. However, the insidious and progressive onset of burn neuropathy makes it often undiagnosed or overlooked. In our study, we reviewed the current studies on the burn-related peripheral neuropathy to summarize the morbidity, mechanism, detecting method and management of peripheral neuropathy in burn patients. Of the 1533 burn patients included in our study, 98 cases (6.39%) were presented with peripheral neuropathy. Thermal and electrical burns were the most common etiologies. Surgical procedures, especially nerve decompression, showed good effect on functional recovery of both acute and delayed peripheral neuropathy in burn patients. It is noteworthy that, for early detection and prevention of peripheral neuropathy, electrodiagnostic examinations should be performed on burn patients independent of symptoms. Still, the underlying mechanisms of burn-related peripheral neuropathy remain to be clarified. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved. ... registry health exam . Research on peripheral neuropathy and herbicides The Health and Medicine Division (HMD) (formally known ... acute or subacute onset may be associated with herbicide exposure. Based on this evidence, VA presumed an ... Baloh, Robert H Peripheral neuropathy is perhaps the archetypal disease of axonal degeneration, characteristically involving degeneration of the longest axons in the body. Evidence from both inherited and acquired forms of peripheral neuropathy strongly supports that the primary pathology is in the axons themselves and points to disruption of axonal transport as an important disease mechanism. Recent studies in human genetics have further identified abnormalities in mitochondrial dynamics--the fusion, fission, and movement of mitochondria--as a player in the pathogenesis of inherited peripheral neuropathy. This review provides an update on the mechanisms of mitochondrial trafficking in axons and the emerging relationship between the disruption of mitochondrial dynamics and axonal degeneration. Evidence suggests mitochondria are a "critical cargo" whose transport is necessary for proper axonal and synaptic function. Importantly, understanding the regulation of mitochondrial movement and the consequences of decreased axonal mitochondrial function may define new paths for therapeutic agents in peripheral neuropathy and other neurodegenerative diseases. Evans, Scott R.; Ellis, Ronald J.; Chen, Huichao; Yeh, Tzu-min; Lee, Anthony J.; Schifitto, Giovanni; Wu, Kunling; Bosch, Ronald J.; McArthur, Justin C.; Simpson, David M.; Clifford, David B. Objectives To estimate neuropathic sign/symptom rates with initiation of combination antiretroviral therapy (cART) in HIV-infected ART-naive patients, and to investigate risk factors for: peripheral neuropathy and symptomatic peripheral neuropathy (SPN), recovery from peripheral neuropathy/SPN after neurotoxic ART (nART) discontinuation, and the absence of peripheral neuropathy/SPN while on nART. Design AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trial participants who initiated cART in randomized trials for ART-naive patients were annually screened for symptoms/signs of peripheral neuropathy. ART use and disease characteristics were collected longitudinally. Methods Peripheral neuropathy was defined as at least mild loss of vibration sensation in both great toes or absent/hypoactive ankle reflexes bilaterally. SPN was defined as peripheral neuropathy and bilateral symptoms. Generalized estimating equation logistic regression was used to estimate associations. Results Two thousand, one hundred and forty-one participants were followed from January 2000 to June 2007. Rates of peripheral neuropathy/SPN at 3 years were 32.1/8.6% despite 87.1% with HIV-1RNA 400 copies/ml or less and 70.3% with CD4 greater than 350 cells/µl. Associations with higher odds of peripheral neuropathy included older patient age and current nART use. Associations with higher odds of SPN included older patient age, nART use, and history of diabetes mellitus. Associations with lower odds of recovery after nART discontinuation included older patient age. Associations with higher odds of peripheral neuropathy while on nART included older patient age and current protease inhibitor use. Associations with higher odds of SPN while on nART included older patient age, history of diabetes, taller height, and protease inhibitor use. Conclusion Signs of peripheral neuropathy remain despite virologic/immunologic control but frequently occurs without symptoms. Aging is a risk factor for Evans, Scott R; Ellis, Ronald J; Chen, Huichao; Yeh, Tzu-min; Lee, Anthony J; Schifitto, Giovanni; Wu, Kunling; Bosch, Ronald J; McArthur, Justin C; Simpson, David M; Clifford, David B To estimate neuropathic sign/symptom rates with initiation of combination antiretroviral therapy (cART) in HIV-infected ART-naive patients, and to investigate risk factors for: peripheral neuropathy and symptomatic peripheral neuropathy (SPN), recovery from peripheral neuropathy/SPN after neurotoxic ART (nART) discontinuation, and the absence of peripheral neuropathy/SPN while on nART. AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trial participants who initiated cART in randomized trials for ART-naive patients were annually screened for symptoms/signs of peripheral neuropathy. ART use and disease characteristics were collected longitudinally. Peripheral neuropathy was defined as at least mild loss of vibration sensation in both great toes or absent/hypoactive ankle reflexes bilaterally. SPN was defined as peripheral neuropathy and bilateral symptoms. Generalized estimating equation logistic regression was used to estimate associations. Two thousand, one hundred and forty-one participants were followed from January 2000 to June 2007. Rates of peripheral neuropathy/SPN at 3 years were 32.1/8.6% despite 87.1% with HIV-1RNA 400 copies/ml or less and 70.3% with CD4 greater than 350 cells/μl. Associations with higher odds of peripheral neuropathy included older patient age and current nART use. Associations with higher odds of SPN included older patient age, nART use, and history of diabetes mellitus. Associations with lower odds of recovery after nART discontinuation included older patient age. Associations with higher odds of peripheral neuropathy while on nART included older patient age and current protease inhibitor use. Associations with higher odds of SPN while on nART included older patient age, history of diabetes, taller height, and protease inhibitor use. Signs of peripheral neuropathy remain despite virologic/immunologic control but frequently occurs without symptoms. Aging is a risk factor for peripheral neuropathy/SPN. Mimi, O; Teng, C L; Chia, Y C This study was undertaken to clinically estimate the prevalence of diabetic peripheral neuropathy amongst patients attending an outpatient clinic and to evaluate their risk factors for developing peripheral neuropathy. It was a cross-sectional study of 134 diabetes mellitus patients who attended the Primary Care Clinic, University Hospital, Kuala Lumpur. The patients were interviewed for their demographic data, past and present medical/surgical history, social history, personal habits and symptoms of peripheral neuropathy. Foot examination and clinical neurological tests were conducted and the presence of peripheral neuropathy was assessed. The main outcome measures were the Neuropathy Symptom Score and the Neuropathy Disability Score. The prevalence of diabetic peripheral neuropathy was found to be 50.7%. Peripheral neuropathy was related to the age of the patient and the duration of diabetes but did not seem to be significantly related to diabetic control. To conclude, there was a high prevalence of peripheral neuropathy amongst the diabetics in this study. These patients developed peripheral neuropathy at a younger age and shorter duration of diabetes compared to a similar study that was done in the UK. Pareyson, Davide; Piscosquito, Giuseppe; Moroni, Isabella; Salsano, Ettore; Zeviani, Massimo Why is peripheral neuropathy common but mild in many mitochondrial disorders, and why is it, in some cases, the predominant or only manifestation? Although this question remains largely unanswered, recent advances in cellular and molecular biology have begun to clarify the importance of mitochondrial functioning and distribution in the peripheral nerve. Mutations in proteins involved in mitochondrial dynamics (ie, fusion and fission) frequently result in a Charcot-Marie-Tooth phenotype. Peripheral neuropathies with different phenotypic presentations occur in mitochondrial diseases associated with abnormalities in mitochondrial DNA replication and maintenance, or associated with defects in mitochondrial respiratory chain complex V. Our knowledge of mitochondrial disorders is rapidly growing as new nuclear genes are identified and new phenotypes described. Early diagnosis of mitochondrial disorders, essential to provide appropriate genetic counselling, has become crucial in a few treatable conditions. Recognising and diagnosing an underlying mitochondrial defect in patients presenting with peripheral neuropathy is therefore of paramount importance. Strong, Amy L; Agarwal, Shailesh; Cederna, Paul S; Levi, Benjamin Peripheral neuropathy and nerve compression syndromes lead to substantial morbidity following burn injury. Patients present with pain, paresthesias, or weakness along a specific nerve distribution or experience generalized peripheral neuropathy. The symptoms manifest at various times from within one week of hospitalization to many months after wound closure. Peripheral neuropathy may be caused by vascular occlusion of vasa nervorum, inflammation, neurotoxin production leading to apoptosis, and direct destruction of nerves from the burn injury. This article discusses the natural history, diagnosis, current treatments, and future directions for potential interventions for peripheral neuropathy and nerve compression syndromes related to burn injury. Copyright © 2017 Elsevier Inc. All rights reserved. Janahi, Noor M; Santos, Derek; Blyth, Christine; Bakhiet, Moiz; Ellis, Mairghread Autoimmunity has been identified in a significant number of neuropathies, such as, proximal neuropathies, and autonomic neuropathies associated with diabetes mellitus. However, possible correlations between diabetic peripheral neuropathy and autoimmunity have not yet been fully investigated. This study was conducted to investigate whether autoimmunity is associated with the pathogenesis of human diabetic peripheral neuropathy. A case-control analysis included three groups: 30 patients with diabetic peripheral neuropathy, 30 diabetic control patients without neuropathy, and 30 healthy controls. Blood analysis was conducted to compare the percentages of positive antinuclear antibodies (ANA) between the three groups. Secondary analysis investigated the correlations between the presence of autoimmune antibodies and sample demographics and neurological manifestations. This research was considered as a pilot study encouraging further investigations to take place in the near future. Antinuclear antibodies were significantly present in the blood serum of patients with diabetic peripheral neuropathy in comparison to the control groups (p<0.001). The odds of positive values of ANA in the neuropathy group were 50 times higher when compared to control groups. Secondary analysis showed a significant correlation between the presence of ANA and the neurological manifestation of neuropathy (Neuropathy symptom score, Neuropathy disability score and Vibration Perception Threshold). The study demonstrated for the first time that human peripheral diabetic neuropathy may have an autoimmune aetiology. The new pathogenic factors may lead to the consideration of new management plans involving new therapeutic approaches and disease markers. Copyright © 2015 Elsevier B.V. All rights reserved. Hypothyroidism: Can it cause peripheral neuropathy? Can hypothyroidism cause peripheral neuropathy and, if so, how is it treated? Answers from Todd B. Nippoldt, M.D. Hypothyroidism — a condition in which your ... Paik, Julie J; Mammen, Andrew L; Wigley, Fredrick M; Shah, Ami A; Hummers, Laura K; Polydefkis, Michael To determine the prevalence of peripheral neuropathy in scleroderma. The prevalence of length-dependent peripheral neuropathy was rigorously assessed using signs and symptoms of neuropathy derived from the Total Neuropathy Score (TNS), and standardized nerve conduction study (NCS). All subjects underwent TNS and NCS. Those who were symptomatic or had NCS evidence of peripheral neuropathy underwent laboratory evaluation for secondary causes of neuropathy. A total of 130 subjects were approached for participation and 60 enrolled. Of the 60 subjects, 50 (83.3%) were female and 37 (61.7%) were of the limited cutaneous subtype. The mean ± SD age was 55 ± 11.1 years, and mean ± SD disease duration was 15.3 ± 10.1 years. A total of 17 of 60 (28%) had evidence of a peripheral neuropathy as defined by the presence of neuropathic symptoms on the TNS (12 of 60) and/or electrophysiologic evidence of neuropathy (5 subjects with neuropathic symptoms and 5 without neuropathic symptoms). Subjects with neuropathy were more likely to be male (60% versus 40%; P = 0.02), African American (41% versus 4.6%; P = 0.001), have diabetes mellitus (17.7% versus 0%; P = 0.02), have limited cutaneous scleroderma (82.3% versus 53.5%; P = 0.04), and have anti-U1 RNP antibodies (23.5% versus 0%; P = 0.009) than those without neuropathy. A potential nonscleroderma etiology for the peripheral neuropathy such as diabetes mellitus was found in 82.3% (14 of 17) of subjects with neuropathy. While symptoms or objective evidence of peripheral neuropathy are common among patients with scleroderma, the cause may often be attributed to comorbid nonscleroderma-related conditions. © 2016, American College of Rheumatology. Helmich, Rick C G; van Laarhoven, Hanneke W M; Schoonderwaldt, Hennie C; Janssen, Mirian C H Rhabdomyolysis and peripheral neuropathy are two distinct disease entities which are rarely encountered in combination. We present a woman with rhabdomyolysis and peripheral neuropathy 3 weeks postpartum. Her symptoms were caused by bilateral femoral artery thrombosis due to postpartum cardiomyopathy (PPCM). This demonstrates that PPCM may present with predominantly non-cardial symptoms and underscores the importance of rapidly recognizing this disorder. Mitochondrial dynamics describes the continuous change in the position, size, and shape of mitochondria within cells. The morphological and functional complexity of neurons, the remarkable length of their processes, and the rapid changes in metabolic requirements arising from their intrinsic excitability render these cells particularly dependent on effective mitochondrial function and positioning. The rules that govern these changes and their functional significance are not fully understood, yet the dysfunction of mitochondrial dynamics has been implicated as a pathogenetic factor in a number of diseases, including disorders of the central and peripheral nervous systems. In recent years, a number of mutations of genes encoding proteins that play important roles in mitochondrial dynamics and function have been discovered in patients with Charcot-Marie-Tooth (CMT) disease, a hereditary peripheral neuropathy. These findings have directly linked mitochondrial pathology to the pathology of peripheral nerve and have identified certain aspects of mitochondrial dynamics as potential early events in the pathogenesis of CMT. In addition, mitochondrial dysfunction has now been implicated in the pathogenesis of noninherited neuropathies, including diabetic and inflammatory neuropathies. The role of mitochondria in peripheral nerve diseases has been mostly examined in vitro, and less so in animal models. This review examines available evidence for the role of mitochondrial dynamics in the pathogenesis of peripheral neuropathies, their relevance in human diseases, and future challenges for research in this field. Staff, Nathan P.; Windebank, Anthony J. Purpose of Review: Peripheral neuropathies secondary to vitamin deficiencies, medications, or toxins are frequently considered but can be difficult to definitively diagnose. Accurate diagnosis is important since these conditions are often treatable and preventable. This article reviews the key features of different types of neuropathies caused by these etiologies and provides a comprehensive list of specific agents that must be kept in mind. Recent Findings: While most agents that cause peripheral neuropathy have been known for years, newly developed medications that cause peripheral neuropathy are discussed. Summary: Peripheral nerves are susceptible to damage by a wide array of toxins, medications, and vitamin deficiencies. It is important to consider these etiologies when approaching patients with a variety of neuropathic presentations; additionally, etiologic clues may be provided by other systemic symptoms. While length-dependent sensorimotor axonal peripheral neuropathy is the most common presentation, several examples present in a subacute severe fashion, mimicking Guillain-Barré syndrome. PMID:25299283 Despite a supposed common mechanism with demyelination, dysimmune peripheral neuropathies compose a heterogeneous group in term of symptoms (sensory, motor, autonomic), localization of lesions (focal, multifocal or widely spreaded) as well as evolutions (acute, relapsing or chronic). The lacks of reliable biological or electrophysiological markers of evolution in dysimmune neuropathies require development of clinical scales for therapeutic trials and therapeutic decisions in daily practice. As elaboration of a universal scale is not a realistic goal, several specific measurement tools have been proposed for dysimmune neuropathies this past ten years. Highlighting the interest of functional scales as the ONLS, the European INCAT group made a remarkable effort to validate these scales in dysimmune neuropathies. However, there is a controversy concerning the relative interest of deficit scales versus functional scales. The deficit scales may be more sensitive to progression of the disease whereas the functional scales reflect the impact of neuropathy. The use of composite scales, mixing the evaluation of deficits, electrophysiological data and functional issues, is a promising solution, but the relative value of these parameters still remains to be defined. Chung, Tae; Prasad, Kalpana; Lloyd, Thomas E. This article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. Magnetic resonance neurography (MRN) has utility in the diagnosis of many focal peripheral nerve lesions. When combined with history, examination, electrophysiology, and laboratory data, future advancements in high-field MRN may play an increasingly important role in the evaluation of patients with peripheral neuropathy. PMID:24210312 Callaghan, Brian C.; Price, Ray S.; Chen, Kevin S.; Feldman, Eva L. Importance Peripheral neuropathy is a prevalent condition that usually warrants a thorough history and examination, but limited diagnostic evaluation. Rare localizations of peripheral neuropathy, however, often require more extensive diagnostic testing and different treatments. Objective To describe rare localizations of peripheral neuropathy, including the appropriate diagnostic evaluation and available treatments. Evidence Review References were identified from PubMed searches with an emphasis on systematic reviews and randomized clinical trials. Articles were also identified through the use of the author's own files. Search terms included common rare neuropathy localizations and their causes, as well as epidemiology, pathophysiology, diagnosis, and treatment. Findings Diffuse, non-length dependent neuropathies, multiple mononeuropathies, polyradiculopathies, plexopathies, and radiculoplexus neuropathies are rare peripheral neuropathy localizations that often require extensive diagnostic testing. Atypical neuropathy features, such as acute/subacute onset, asymmetry, and/or motor predominant signs, are frequently present. The most common diffuse, non-length dependent neuropathies are Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and amyotrophic lateral sclerosis (ALS). Effective disease modifying therapies exist for many diffuse, non-length dependent neuropathies including GBS, CIDP, MMN, and some paraprotein-associated demyelinating neuropathies. Vasculitic neuropathy (multiple mononeuropathy) also has efficacious treatment options, but definitive evidence of a treatment effect for IgM anti-MAG neuropathy and diabetic amyoptrophy (radiculoplexus neuropathy) is lacking. Conclusions and Relevance Recognition of rare localizations of periperhal neuropathy is essential given the implications for diagnostic testing and treatment. Electrodiagnostic studies are an important early step in the Klein, Christopher J Peripheral neuropathies have diverse acquired and inherited causes. The autoimmune neuropathies represent an important category where treatment is often available. There are overlapping signs and symptoms between autoimmune neuropathies and other forms. Making a diagnosis can be challenging and first assisted by electrophysiologic and sometimes pathologic sampling, with autoimmune biomarkers providing increased assistance. Here we provide a review of the autoimmune and inflammatory neuropathies, their available biomarkers, and approaches to treatment. Also discussed is new evidence to support a mechanism of autoimmune pain. © 2016 Elsevier B.V. All rights reserved. Juster-Switlyk, Kelsey; Smith, A. Gordon Diabetes has become one of the largest global health-care problems of the 21 st century. According to the Centers for Disease Control and Prevention, the population prevalence of diabetes in the US is approaching 10% and is increasing by 5% each year. Diabetic neuropathy is the most common complication associated with diabetes mellitus. Diabetes causes a broad spectrum of neuropathic complications, including acute and chronic forms affecting each level of the peripheral nerve, from the root to the distal axon. This review will focus on the most common form, distal symmetric diabetic polyneuropathy. There has been an evolution in our understanding of the pathophysiology and the management of diabetic polyneuropathy over the past decade. We highlight these new perspectives and provide updates from the past decade of research. PMID:27158461 Juster-Switlyk, Kelsey; Smith, A Gordon Diabetes has become one of the largest global health-care problems of the 21 (st) century. According to the Centers for Disease Control and Prevention, the population prevalence of diabetes in the US is approaching 10% and is increasing by 5% each year. Diabetic neuropathy is the most common complication associated with diabetes mellitus. Diabetes causes a broad spectrum of neuropathic complications, including acute and chronic forms affecting each level of the peripheral nerve, from the root to the distal axon. This review will focus on the most common form, distal symmetric diabetic polyneuropathy. There has been an evolution in our understanding of the pathophysiology and the management of diabetic polyneuropathy over the past decade. We highlight these new perspectives and provide updates from the past decade of research. Ng Wing Tin, Sophie; Ciampi de Andrade, Daniel; Goujon, Colette; Planté-Bordeneuve, Violaine; Créange, Alain; Lefaucheur, Jean-Pascal To characterize sensory threshold alterations in peripheral neuropathies and the relationship between these alterations and the presence of pain. Seventy-four patients with length-dependent sensory axonal neuropathy were enrolled, including 38 patients with painful neuropathy (complaining of chronic, spontaneous neuropathic pain in the feet) and 36 patients with painless neuropathy. They were compared to 28 age-matched normal controls. A standardized quantitative sensory testing protocol was performed in all individuals to assess large and small fiber function at the foot. Large fibers were assessed by measuring mechanical (pressure and vibration) detection thresholds and small fibers by measuring pain and thermal detection thresholds. Between patients with neuropathy and controls, significant differences were found for mechanical and thermal detection thresholds but not for pain thresholds. Patients with painful neuropathy and those with painless neuropathy did not differ regarding mechanical or thermal thresholds, but only by a higher incidence of thermal or dynamic mechanical allodynia in case of painful neuropathy. Pain intensity correlated with the alteration of thermal detection and mechanical pain thresholds. Quantitative sensory testing can support the diagnosis of sensory neuropathy when considering detection threshold measurement. Thermal threshold deterioration was not associated with the occurrence of pain but with its intensity. There is a complex relationship between the loss or functional deficit of large and especially small sensory nerve fibers and the development of pain in peripheral neuropathy. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. Rosenberg, Casandra J; Watson, James C Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. To discuss current treatment recommendations for painful diabetic peripheral neuropathy. Literature review. Systematic review of the literature discussing treatment of painful diabetic peripheral neuropathy. Existing treatment guidelines were studied and compared. Painful diabetic peripheral neuropathy occurs in about one in six people with diabetes. This condition impairs quality of life and increases healthcare costs. Treatment recommendations exist, but individual patient therapy can require a trial-and-error approach. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. Adequate medication titration and a reasonable trial period should be allowed. The treatment of painful diabetic peripheral neuropathy can be challenging, but effective management can improve patient's quality of life. Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. © The International Society for Prosthetics and Orthotics 2014. Sonnino, Sandro; Chiricozzi, Elena; Ciampa, Maria Grazia; Mauri, Laura; Prinetti, Alessandro; Toffano, Gino; Aureli, Massimo In peripheral neuropathies, such as sensorimotor neuropathies, motor neuron diseases, or the Guillain-Barré syndrome, serum antibodies recognizing saccharide units, portion of oligosaccharides, or oligosaccharide chains, have been found. These antibodies are called anti-glycosphingolipid (GSL) or anti-ganglioside antibodies. However, the information on the aglycone carrying the hydrophilic oligosaccharide remains elusive. The absolute and unique association of GSL to the onset, development and symptomatology of the peripheral neuropathies could be misleading. Here, we report some thoughts on the matter. Trivedi, Sweety; Pandit, Alak; Ganguly, Goutam; Das, Shyamal Kumar Peripheral neuropathy (PN) is a common disorder and presents as diagnostic and therapeutic challenge to physicians and neurologists. In epidemiological studies from India from various regions the overall prevalence of PN varied from 5 to 2400 per 10,000 population in various community studies. India is composed of a multiethnic, multicultural population who are exposed to different adverse environmental factors such as arsenic and lead. Use of different chemotherapeutic agents with propensity to affect peripheral nerves, increasing methods of diagnosis of connective tissue disorders and use of immunomodulating drugs, growing aging population is expected to change the spectrum and burden of peripheral neuropathy in the community. The other important aspect of peripheral neuropathies is in terms of the geographical and occupational distribution especially of toxic neuropathies like arsenic which is common in eastern belt; lead, mercury and organo-phosphorous compounds where occupational exposures are major sources. Inflammatory neuropathies either due to vasculitis or G B Syndrome, chronic inflammatory polyradiculopathies are another major group of neuropathies which is increasing due to increase longevity of Indian subjects and immunological impairment, also adds to morbidity of the patients and are potentially treatable. Leprous neuropathy is common in India and although its frequency is significantly decreasing because of national control program yet pure neuritic form still remains a cause of concern and similar is the case with another infective cause like diptheric neurpathy. Thus this article is an attempt to cover major categories and also highlight the areas where further studies are needed. PMID:28904445 Marmiroli, Paola; Cavaletti, Guido Peripheral neuropathies are frequent in association with systemic diseases as well as isolated disorders. Recent advances in the therapy of specific neuropathies led to the approval of new drugs/treatments. This review selected those peripheral neuropathies where the most recent approvals were provided and revised the potential future developments in diabetic and toxic-induced neuropathies, although they do not have a currently available causal therapy in view of their epidemiological and social relevance. Data have been extracted from the most important published trials and from clinical experience. In addition, data from the Food and Drug Administration and European Medicine Agency indications on the treatment of the selected peripheral neuropathies and from recently updated international guidelines have also been included. The website of the U.S. National Institutes of Health www.clinicaltrials.gov registry has been used as the reference database for phase III clinical trials not yet published or ongoing. This review gives a general overview of the most recent advances in the treatment of amyloid, inflammatory, and paraproteinemic peripheral neuropathies. Moreover, it briefly describes the unmet medical need in disabling and frequent conditions, such as diabetic and chemotherapy-induced neuropathy, highlighting the most promising therapeutic approaches to their treatment. Monastiriotis, Christodoulos; Papanas, Nikolaos; Veletza, Stavroula; Maltezos, Efstratios Genetic factors may influence the natural course of diabetic peripheral neuropathy and explain some of its variability. The aim of this review was to examine the association between apolipoprotein E (apoE) gene polymorphisms and diabetic peripheral neuropathy. Four relevant studies were identified. The two earlier works provided evidence that the ɛ4 allele is a risk factor for this complication, while the two more recent studies were negative. Important differences in the methodology used and in the populations included are obvious, rendering difficult the comparison between studies. In conclusion, the association between APOE gene polymorphisms and diabetic peripheral neuropathy is still unclear. Available evidence is rather limited and results have so far been contradictory. Future studies should employ more robust methodology, adjusting for potential confounders and for the prevalence of neuropathy in the general population with diabetes. Pope, Karl; So, Yuen T; Crane, Julian; Bates, Michael N The mechanism of toxicity of hydrogen sulfide (H2S) gas is thought mainly to operate through effects on the nervous system. The gas has high acute toxicity, but whether chronic exposure causes effects, including peripheral neuropathy, is yet unclear. The city of Rotorua, New Zealand, sits on an active geothermal field and the population has some of the highest measured ambient H2S exposures. A previous study in Rotorua provided evidence that H2S is associated with peripheral neuropathy. Using clinical methods, the present study sought to investigate and possibly confirm this association in the Rotorua population. The study population comprised 1635 adult residents of Rotorua, aged 18-65. Collected data relevant to the peripheral neuropathy investigation included symptoms, ankle stretch reflex, vibration sensitivity, as measured by the timed-tuning fork test and a Bio-Thesiometer (Bio-Medical Instrument Co., Ohio), and light touch sensitivity measured by monofilaments. An exposure metric, estimating time-weighted H2S exposure across the last 30 years was used. Principal components analysis was used to combine data across the various indicators of possible peripheral neuropathy. The main data analysis used linear regression to examine associations between the peripheral nerve function indicators and H2S exposure. None of the peripheral nerve function indicators were associated with H2S exposure, providing no evidence that H2S exposure at levels found in Rotorua is a cause of peripheral neuropathy. The earlier association between H2S exposure and peripheral neuropathy diagnoses may be attributable to the ecological study design used. The possibility that H2S exposure misclassification could account for the lack of association found cannot be entirely excluded. Copyright © 2017 Elsevier B.V. All rights reserved. Sarker, U K; Uddin, M J; Chowdhury, R; Roy, N; Bhattacharjee, M; Roy, J The objectives of the study were to see the association of peripheral neuropathy in leprosy and to find out the clinical profile of peripheral neuropathy and disability status in leprosy. It was descriptive type of cross sectional study was conducted among the cases of leprosy attended in the out-patient departments of neurology, Mymensingh Medical College Hospital (MMCH) and Mymensingh tuberculosis and leprosy hospital that fulfilled the inclusion criteria were included in this study, during the study period of January 2010 to December 2011.In this study of 62 cases revealed that leprosy is more common in male (71%) people and 21% leprosy patient had contact with known case of leprosy. Leprosy causes peripheral neuropathy (61.3%). Duration of occurrence of peripheral neuropathy was prolonged (>6 month) in most of the patients (47.4%) and the disease progression was also slow (63.2%). Numbness was complained by 89.4% patients and 65.8% subjects complained of weakness of limbs. Deformities and ulcers were present in 26.3% and 50% of patients respectively. Ulnar nerve (43.6%), Lateral popliteal nerve (41.9%), Posterior tibial nerve (41.9%) and Great auricular nerve (17.7%) were the most commonly involved thickened peripheral nerves. The rate of visible physical impairment (WHO Grade 2 disability) among people affected by leprosy in feet was 27.4% and in hands was 16.1%. The position and vibration sense was found to normal all patients of peripheral neuropathy. Calcutt, Nigel A.; Lopez, Veronica L.; Bautista, Arjel D.; Mizisin, Leah M.; Torres, Brenda R.; Shroads, Albert L.; Mizisin, Andrew P.; Stacpoole, Peter W. The use of dichloroacetate (DCA) for treating patients with mitochondrial diseases is limited by the induction of peripheral neuropathy. The mechanisms of DCA-induced neuropathy are not known. Oral DCA treatment (50–500 mg/kg/day for up to 16 weeks) induced tactile allodynia in both juvenile and adult rats; concurrent thermal hypoalgesia developed at higher doses. Both juvenile and adult rats treated with DCA developed nerve conduction slowing that was more pronounced in adult rats. No overt axonal or glial cell abnormalities were identified in peripheral nerves or spinal cord of any DCA-treated rats but morphometric analysis identified a reduction of mean axonal caliber of peripheral nerve myelinated fibers. DCA treatment also caused accumulation of oxidative stress markers in the nerves. These data indicate that behavioral, functional and structural indices of peripheral neuropathy may be induced in both juvenile and adult rats treated with DCA at doses similar to those in clinical use. DCA-induced peripheral neuropathy primarily afflicts axons and involves both metabolic and structural disorders. The DCA-treated rat may provide insight into the pathogenesis of peripheral neuropathy and facilitate development of adjuvant therapeutics to prevent this disorder that currently restricts the clinical use of DCA. PMID:19680144 Kramer, Rita; Bielawski, Jacek; Kistner-Griffin, Emily; Othman, Alaa; Alecu, Irina; Ernst, Daniela; Kornhauser, Drew; Hornemann, Thorsten; Spassieva, Stefka Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and cisplatin chemotherapy. In the current study, we tested the involvement of a novel class of neurotoxic sphingolipids, the 1-deoxysphingolipids. 1-Deoxysphingolipids are produced when the enzyme serine palmitoyltransferase uses l-alanine instead of l-serine as its amino acid substrate. We tested whether treatment of cells with paclitaxel (250 nM, 1 µM) and cisplatin (250 nM, 1 µM) would result in elevated cellular levels of 1-deoxysphingolipids. Our results revealed that paclitaxel, but not cisplatin treatment, caused a dose-dependent elevation of 1-deoxysphingolipids levels and an increase in the message and activity of serine palmitoyltransferase (P < 0.05). We also tested whether there is an association between peripheral neuropathy symptoms [evaluated by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-chemotherapy-induced peripheral neuropathy-20 (CIPN20) instrument] and the 1-deoxysphingolipid plasma levels (measured by mass spectrometry) in 27 patients with breast cancer who were treated with paclitaxel chemotherapy. Our results showed that there was an association between the incidence and severity of neuropathy and the levels of very-long-chain 1-deoxyceramides such as C24 (P < 0.05), with the strongest association being with motor neuropathy (P < 0.001). Our data from cells and from patients with breast cancer suggest that 1-deoxysphingolipids, the very-long-chain in particular, play a role as molecular intermediates of paclitaxel-induced peripheral neuropathy.—Kramer, R., Bielawski, J., Kistner-Griffin, E., Othman, A., Alecu, I., Ernst, D., Kornhauser, D., Hornemann, T., Spassieva, S. Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy. PMID:26198449 Singh, Randhir; Kishore, Lalit; Kaur, Navpreet Diabetic neuropathy is a heterogeneous group of disorders with extremely complex pathophysiology and affects both somatic and autonomic components of the nervous system. Neuropathy is the most common chronic complication of diabetes mellitus. Metabolic disruptions in the peripheral nervous system, including altered protein kinase C activity, and increased polyol pathway activity in neurons and Schwann cells resulting from hyperglycemia plays a key role in the development of diabetic neuropathy. These pathways are related to the metabolic and/or redox state of the cell and are the major source of damage. Activation of these metabolic pathways leads to oxidative stress, which is a mediator of hyperglycemia induced cell injury and a unifying theme for all mechanisms of diabetic neuropathy. The therapeutic intervention of these metabolic pathways is capable of ameliorating diabetic neuropathy but therapeutics which target one particular mechanism may have a limited success. Available therapeutic approaches are based upon the agents that modulate pathogenetic mechanisms (glycemic control) and relieve the symptoms of diabetic neuropathy. This review emphasizes the pathogenesis, presently available therapeutic approaches and future directions for the management of diabetic neuropathy. Starobova, Hana; Vetter, Irina Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches. PMID:28620280 Fernyhough, Paul; Calcutt, Nigel A. Abnormal neuronal calcium (Ca2+) homeostasis has been implicated in numerous diseases of the nervous system. The pathogenesis of two increasingly common disorders of the peripheral nervous system, namely neuropathic pain and diabetic polyneuropathy, has been associated with aberrant Ca2+ channel expression and function. Here we review the current state of knowledge regarding the role of Ca2+ dyshomeostasis and associated mitochondrial dysfunction in painful and diabetic neuropathies. The central impact of both alterations of Ca2+ signalling at the plasma membrane and also intracellular Ca2+ handling on sensory neuron function is discussed and related to abnormal endoplasmic reticulum performance. We also present new data highlighting sub-optimal axonal Ca 2+ signalling in diabetic neuropathy and discuss the putative role for this abnormality in the induction of axonal degeneration in peripheral neuropathies. The accumulating evidence implicating Ca2+ dysregulation with both painful and degenerative neuropathies, along with recent advances in understanding of regional variations in Ca2+ channel and pump structures, makes modulation of neuronal Ca2+ handling an increasingly viable approach for therapeutic interventions against the painful and degenerative aspects of many peripheral neuropathies. PMID:20034667 Addington, James; Freimer, Miriam Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects. Addington, James; Freimer, Miriam Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects. PMID:27408692 Thiam, A; Diagne, M; Ndiaye, Ng; Ngom Gueye, N F; Diakhate, N D; Sow, P S; Ndiaye, I P In order to appreciate the antiretroviral drugs impact in the HIV positive patients with peripheral neuropathy, a clinical, electrophysiological and neurpathological study of nerve biopsies was performed. A group of 8 HIV seropositive patients with peripheral neuropathy was compared with an other group of 10 HIV seropositive patients treated with multiple antiretroviral drugs. Electrophysiological examination with motor nerve conduction velocity (MNCV) mesure of the median and the sciatic popliteal nerve was followed by nerve biopsy. Nerve fragments carried out the neuropathological technics for morphological examination. Eighteen seropositive HIV patients (16 HIV-1 and 2 HIV-2) were included in this study. Six patients among them had motor and sensitive neuropathy of the four limbs and 2 patients had sensitive neuropathy associated with pyramidal signs. In fine, 1 patient had sensitive neuropathy with distal amyotrophy of the four limbs. Slow MNCV was observed in all the patients and more severe in the lower limbs. Nerve were unexciting in the lower limbs in 2 patients. Nerve biopsy showed severe axonal loss in all the patients treated but one. They associated axonal lesion in 5 cases and myelinated lesions in 2 cases. Two patients non treated had normal nerve biopsy. Axonal loss was mild in 2 cases and very severe in one case associated with non inflammatory demyelinated lesions. we observed more severe and more frequent nerve lesions in treated patients than in no treated patients, as at the clinical, electrophysiological and neuropathological examination. Antiretroviral drugs cause more frequently pain motor and sensitive neuropathies at usual posologies. The occurence of recrudescence of pain peripheral neuropathy under antiretroviral treatment allows to reconsider drugs posologies. Hoeijmakers, Janneke G J; Faber, Catharina G; Merkies, Ingemar S J; Waxman, Stephen G Peripheral neuropathy can lead to neuropathic pain in a subset of patients. Painful peripheral neuropathy is a debilitating disorder, reflected by a reduced quality of life. Therapeutic strategies are limited and often disappointing, as in most cases targeted treatment is not available. Elucidating pathogenetic factors for pain might provide a target for optimal treatment. Voltage-gated sodium channels NaV1.7-NaV1.9 are expressed in the small-diameter dorsal root ganglion neurons and their axons. By a targeted gene approach, missense gain-of-function mutations of NaV1.7-NaV1.9 have been demonstrated in painful peripheral neuropathy. Functional analyses have shown that these mutations produce a spectrum of pro-excitatory changes in channel biophysics, with the shared outcome at the cellular level of dorsal root ganglion hyperexcitability. Reduced neurite outgrowth may be another consequence of sodium channel mutations, and possible therapeutic strategies include blockade of sodium channels or block of reverse operation of the sodium-calcium exchanger. Increased understanding of the pathophysiology of painful peripheral neuropathy offers new targets that may provide a basis for more effective treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved. Erbas, Tomris; Ertas, Mustafa; Yucel, Aysen; Keskinaslan, Abdulkadir; Senocak, Mustafa The aim of this study was to determine the prevalence of diabetic peripheral neuropathy (DPN) and neuropathic pain in diabetic patients attending university outpatient clinics in Turkey. In this multicenter cross-sectional study, neurologic examinations and nerve conduction studies along with clinical diabetic neuropathy score, and Leeds Assessment of Neuropathic Symptoms and Signs pain scale were performed on 1,113 patients (46.2% male) from 14 centers. Prevalence of DPN determined only by clinical examination was 40.4% and increased to 62.2%, by combining nerve conduction studies with clinical examination. According to Leeds Assessment of Neuropathic Symptoms and Signs scores, neuropathic pain prevalence was 16.0% in those who reported pain. Poor glycemic control, retinopathy, microalbuminuria, hyperlipidemia, diabetic foot, and foot amputation were more commonly observed in patients with DPN. Clinical DPN affected 40.4% of diabetic patients, and neuropathic pain prevalence in diabetic patient population was 14.0%. Clinical examinations and nerve conduction studies are important components for early detection and accurate diagnosis of DPN and painful DPN. Jayaprakash, P; Bhansali, Anil; Bhansali, Shobhit; Dutta, Pinaki; Anantharaman, R; Shanmugasundar, G; Ravikiran, M Vibration perception threshold (VPT) is considered as a gold standard for diagnosis of diabetic peripheral neuropathy. However, the data are sparse comparing the VPT with commonly used bedside modalities. This study was carried out to evaluate the usefulness of simple bed side screening modalities for peripheral neuropathy in patients with diabetes mellitus. A total of 1044 patients with diabetes mellitus attending the Diabetes clinic from January 2007 to May 2008, were included in this study. All subjects had a detailed clinical assessment including Diabetic Neuropathy Symptom (DNS) score, Diabetic Neuropathy Examination (DNE) score, ankle reflex, vibration sensation with a 128 Hz tuning fork, 10 g Semmes-Weinstein monofilament and vibration perception threshold (VPT). The prevalence of peripheral neuropathy was 34.9 per cent with VPT. Foot care practices were followed by only 214 (20.5%) of the study population. When compared with VPT, ankle reflex was the most sensitive (90.7%) but least specific (37.3%). The tuning fork and monofilament tests respectively had lower sensitivity (62.5 and 62.8%) but better specificity (95.3 and 92.9%) and accuracy (78.9 and 77.9%). Significant correlations were observed between the VPT score and the DNE (r = 0.532, P<0.001) and DNS (r = 0.546, P<0.001) scores and absent tuning fork sensation (r = 0.590; P<0.001), monofilament sensation (r = 0.573; P<0.001) and ankle reflex (r = 0.377, P = 0.01). The present findings show that simple bed side tests are useful for assessing peripheral diabetic neuropathy, even in those subjects in whom foot care practices are not followed. Kramer, Rita; Bielawski, Jacek; Kistner-Griffin, Emily; Othman, Alaa; Alecu, Irina; Ernst, Daniela; Kornhauser, Drew; Hornemann, Thorsten; Spassieva, Stefka Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and cisplatin chemotherapy. In the current study, we tested the involvement of a novel class of neurotoxic sphingolipids, the 1-deoxysphingolipids. 1-Deoxysphingolipids are produced when the enzyme serine palmitoyltransferase uses l-alanine instead of l-serine as its amino acid substrate. We tested whether treatment of cells with paclitaxel (250 nM, 1 µM) and cisplatin (250 nM, 1 µM) would result in elevated cellular levels of 1-deoxysphingolipids. Our results revealed that paclitaxel, but not cisplatin treatment, caused a dose-dependent elevation of 1-deoxysphingolipids levels and an increase in the message and activity of serine palmitoyltransferase (P < 0.05). We also tested whether there is an association between peripheral neuropathy symptoms [evaluated by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-chemotherapy-induced peripheral neuropathy-20 (CIPN20) instrument] and the 1-deoxysphingolipid plasma levels (measured by mass spectrometry) in 27 patients with breast cancer who were treated with paclitaxel chemotherapy. Our results showed that there was an association between the incidence and severity of neuropathy and the levels of very-long-chain 1-deoxyceramides such as C24 (P < 0.05), with the strongest association being with motor neuropathy (P < 0.001). Our data from cells and from patients with breast cancer suggest that 1-deoxysphingolipids, the very-long-chain in particular, play a role as molecular intermediates of paclitaxel-induced peripheral neuropathy. © FASEB. Sykam, Aparna; Gutlapalli, V R; Tenali, Sandeep P; Meena, A K; Chandran, Priscilla; Suneetha, Sujai; Suneetha, Lavanya M Ceramide is a glycosphingolipid, a component of nerve and non neuronal cell membrane and plays a role in maintaining the integrity of neuronal tissue. Butyrylcholinesterase (BChE) is a multifunctional enzyme, its involvement in neurodegenerative diseases has been well established. Anticeramide antibody (Ab-Cer) and enzyme BChE have been implicated in peripheral neuropathies. The present study investigates whether there is an association between Ab-Cer and BChE activities and peripheral neuropathies. Patients included: human immunodeficiency virus associated peripheral neuropathy (HIV-PN, n=39), paucibacillary leprosy (PB-L, n=36), multibacillary leprosy (MB-L, n=52), diabetic neuropathy (DN, n=22), demyelinating sensory motor polyneuropathy (DSMN, n=13) and chronic inflammatory demyelinating polyneuropathy (CIDP, n=10). Plasma Ab-Cer was measured by indirect enzyme linked immune assay (ELISA) and BChE activity in plasma was measured by colorimetric method. Ab-Cer levels were significantly elevated in MB-L and DN as compared to healthy subjects (HS). BChE levels were significantly higher in MB-L and DN as well as in HIV and HIV-PN. There is no significant difference in either Ab-Cer or BChE levels in DSMN and CIDP. Elevated plasma Ab-Cer and BChE levels may be considered significant in the pathogenesis of neuropathies. The variation in concurrent involvement of both the molecules in the neuropathies of the study, suggest their unique involvement in neurodegenerative pathways. Copyright © 2017 Elsevier Ltd. All rights reserved. Kerasnoudis, Antonios; Tsivgoulis, Georgios Peripheral neuropathies are one of the most common reasons for seeking neurological care in everyday practice. Electrophysiological studies remain fundamental for the diagnosis and etiological classification of peripheral nerve impairment. The recent technological development though of high resolution ultrasound has allowed the clinician to obtain detailed structural images of peripheral nerves. Nerve ultrasound mainly focuses on the evaluation of the cross sectional area, cross sectional area variability along the anatomical course, echogenity, vascularity and mobility of the peripheral nerves. An increase of the cross sectional area, hypervascularity, disturbed fascicular echostructure and reduced nerve mobility are some of the most common findings of entrapments neuropathies, such as the carpal or cubital tunnel syndrome. Both the cross-sectional area increase and the hypervascularity detected with the Doppler technique seem to correlate significantly with the clinical and electrophysiological severity of the later mononeuropathies. Significantly greater cross sectional area values of the clinically affected cervical nerve root are often detected in cases of cervical radiculopathy. In such cases, the ultrasound findings seem also to correlate significantly with disease duration. On the other hand, multifocal cross sectional area enlargement of cervical roots and/or peripheral nerves is often documented in cases of immune-mediated neuropathies. None of the later pathological ultrasound findings seem to correlate significantly with the electrophysiological parameters or the functional disability. The aim of this review is to provide a timely update on the role of neuromuscular ultrasound in the diagnostic of the most common entrapment and immune-mediated peripheral neuropathies in clinical practice. Copyright © 2015 by the American Society of Neuroimaging. Iżycki, Dariusz; Niezgoda, Adam; Kaźmierczak, Maciej; Nowak-Markwitz, Ewa Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most important neurologic complications experienced by patients receiving chemotherapy. The neuropathy often interferes with daily activities and exercise leading to severe impairment of the patient's quality of life (QoL). The evolution of most CIPNs is characterized by a gradual onset of signs/symptoms, beginning in the lower limbs and advancing proximally into a bilateral stocking and glove distribution. Patients often complain of numbness, tingling and pain in the affected areas. The symptoms become aggravated with repeated cycles of chemotherapy. When the offending agent is withheld, the symptoms generally abate, but relief is not guaranteed. The consequences of delay or discontinuation of treatment may affect overall patient survival. Pagano, Lucia; Proietto, Maria; Biondi, Roberto About 60 to 70 percent of people with diabetes have some neuropathy. Diabetic neuropathy can be classified as peripheral, autonomic, proximal, focal and multifocal or mixed. Peripheral neuropathy, the most common type of diabetic neuropathy, causes pain and/or loss of feeling in the toes, feet, legs, hands, and arms; extreme sensitivity to touch, loss of balance and coordination; muscle weakness and loss of reflexes, especially at the ankle, leading to changes in the way a person walks. The aim of this study is to underline the importance of drug and rehabilitative approach in the therapy of peripheral neuropathy, that frequently influences both diabetes mellitus type 1 and diabetes mellitus type 2. Nicholas, Patrice K; Corless, Inge B; Evans, Linda A Peripheral neuropathy is a common and vexing symptom for people living with HIV infection (PLWH). Neuropathy occurs in several different syndromes and is identified in the literature as distal sensory polyneuropathy or distal sensory peripheral neuropathy. More recently, the HIV literature has focused on the syndrome as painful HIV-associated sensory neuropathy, addressing the symptom rather than the underlying pathophysiology. Assessment of neuropathy in PLWH is critical and must be incorporated into nursing practice for each visit. Neuropathy has been attributed to the direct effects of HIV, exposure to antiretroviral medications (particularly the nucleoside reverse transcriptase inhibitors), advanced immune suppression, and comorbid tuberculosis infection and exposure to antituberculosis medications. Evidence supports the importance of addressing neuropathy in PLWH with pharmacologic treatment regimens and complementary/alternative approaches. This paper examines the pathophysiology, evidence, and approaches to managing peripheral neuropathy. A case study has been included to illustrate a patient's experience with neuropathy symptoms. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved. Papapetrou, Peter; Kumar, Aashish J; Muppuri, Rudram; Chakrabortty, Shushovan Chemotherapy-induced peripheral neuropathy is a debilitating side effect of chemotherapy, which manifests as paresthesias, dysesthesias, and numbness in the hands and feet. Numerous chemoprotective agents and treatments have been used with limited success to treat chemotherapy-induced peripheral neuropathy. We report a case in which a patient presenting with chemotherapy-induced peripheral neuropathy received an IV lidocaine infusion over the course of 60 minutes with complete symptomatic pain relief for a prolonged period of 2 weeks. Goolsby, Tiffany A; Jakeman, Bernadette; Gaynes, Robert P The objective of this paper was to review and evaluate the literature on metronidazole-associated peripheral neuropathy and determine the relevance in clinical practice. MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity. Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources. Overall, metronidazole is generally well tolerated but serious neurotoxicity, including peripheral neuropathy, has been reported. The overall incidence of peripheral neuropathy associated with metronidazole is unknown. Our review found 36 case reports (40 unique patients) of metronidazole-associated peripheral neuropathy with the majority of cases receiving >42 total grams (>4 weeks) of therapy (31 out of 40). In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0-50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 total grams (>4 weeks) of metronidazole compared to those patients receiving ≤ 42 total grams (17.9% vs 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is exceedingly rare in patients who receive ≤ 42 total grams of metronidazole. Patients who receive larger total doses may be at higher risk of peripheral neuropathy but most patients have resolution of symptoms after discontinuing therapy. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 grams of the drug (≤4 weeks). Copyright © 2017. Published by Elsevier B.V. Misiunas, A; Niepomniszcze, H; Ravera, B; Faraj, G; Faure, E Alterations in peripheral nerves are well documented in overt myxedema but not in subclinical hypothyroidism. We performed electrophysiologic studies to investigate such abnormalities in patients with normal serum total T4 and hyperresponsiveness of TSH to TRH, either with normal or high levels of basal circulating TSH. Subjects were divided in three groups: (i) Hypothyroidism Stage I (group () (n = 17, mean age = 39 +/- 34 years), T4 = 9 +/- 0.7 micrograms/dL, TSH = 4.3 +/- 0.4 microU/mL, sTSH post-TRH (peak value) = 37.6 +/- 1.6 microU/mL; (ii) Hypothyroidism Stage II (group II) (n = 10, mean age: 43 +/- 6 years), T4 = 7.7 +/- 0.8 microgram/dL, TSH = 20 +/- 5 microU/mL, TSH post-TRH > 50 microU/mL; (iii) Control Group (n = 20, mean age 41 +/- 5 years), healthy subjects. All patients and controls were women. TRH test consisted in the i.v. injection of 200 micrograms TRH (normal peak value up to 25 microU/mL, normal basal TSH < 5.5 microU/mL. None of the patients had carpal tunnel syndrome or any other neurological or metabolic disturbances. We studied the distal motor latencies, motor and sensory amplitudes, and nerve conduction velocities. The motor parameters were measured in the median and external sciatic popliteal (ESP) nerves, and the sensory parameters in the median and sural nerves. In most cases values were obtained from both right and left nerves. Motor parameters: no differences were found between all groups for conduction velocities (CV).(ABSTRACT TRUNCATED AT 250 WORDS) Chiles, Nancy S.; Phillips, Caroline L.; Volpato, Stefano; Bandinelli, Stefania; Ferrucci, Luigi; Guralnik, Jack M.; Patel, Kushang V. Objective Diabetes among older adults causes many complications, including decreased lower extremity function and physical disability. Diabetes can cause peripheral nerve dysfunction, which might be one pathway through which diabetes leads to decreased physical function. The study aims were to determine: (1) whether diabetes and impaired fasting glucose are associated with objective measures of physical function in older adults, (2) which peripheral nerve function (PNF) tests are associated with diabetes, and (3) whether PNF mediates the diabetes-physical function relationship. Research Design and Methods This study included 983 participants, age 65 and older from the InCHIANTI Study. Diabetes was diagnosed by clinical guidelines. Physical performance was assessed using the Short Physical Performance Battery (SPPB), scored from 0-12 (higher values, better physical function) and usual walking speed (m/s). PNF was assessed via standard surface electroneurographic study of right peroneal nerve conduction velocity, vibration and touch sensitivity. Clinical cut-points of PNF tests were used to create a neuropathy score from 0-5 (higher values, greater neuropathy). Multiple linear regression models were used to test associations. Results and Conclusion 12.8% (n=126) of participants had diabetes. Adjusting for age, sex, education, and other confounders, diabetic participants had decreased SPPB (β= −0.99; p< 0.01), decreased walking speed (β= −0.1m/s; p< 0.01), decreased nerve conduction velocity (β= −1.7m/s; p< 0.01), and increased neuropathy (β= 0.25; p< 0.01) compared to non-diabetic participants. Adjusting for nerve conduction velocity and neuropathy score decreased the effect of diabetes on SPPB by 20%, suggesting partial mediation through decreased PNF. PMID:24120281 Frisk, P; Stålberg, E; Strömberg, B; Jakobson A Ifosfamide is successfully employed in the treatment of bone and soft tissue sarcomas in children and young adults. Used at high doses (HDI) the drug may cause severe multiorgan toxicity. Peripheral neuropathy is a less well-known side effect that may limit its use. We describe a 16-year-old girl with a Ewing sarcoma who was given post-operative treatment with HDI (15 mg/m(2) infused over 5 days). After the second course she experienced paresthesias in both feet. After the third course she developed signs of severe toxicity in the CNS, kidneys, heart, and severe pain in her feet. Neurologic and neurophysiologic investigations, including neurographic studies of motor and sensory nerves, EMG, and thermotest, were performed in the acute phase and after 6 and 21 months, respectively. Renal and cardiac function was also assessed. She developed generalized weakness of the arms and legs and an extremely painful hyperesthesia of the soles. The symptoms improved gradually during follow-up but remained to some extent even after more than 2 years. Serial neurophysiologic investigations indicated classical signs of axonal neuropathy, which tended to improve during follow-up. After 18 months the glomerular filtration rate and the effective renal plasma flow were 30 and 12% of normal, respectively, while other organ functions had returned to baseline. Symptoms of peripheral neuropathy after HDI may herald severe multiorgan toxicity, if continued. Early administration of anesthetics through the intrathecal route should be considered in case of ifosfamide-induced painful peripheral neuropathy. Copyright 2001 Wiley-Liss, Inc. Fateh, Hamid R; Madani, Seyed Pezhman; Heshmat, Ramin; Larijani, Bagher Almost half of Diabetic Peripheral Neuropathies (DPNs) are symptom-free. Methods including questionnaires and electrodiagnosis (EDx) can be fruitful for easy reach to early diagnosis, correct treatments of diabetic neuropathy, and so decline of complications for instance diabetic foot ulcer and prevention of high costs. The goal of our study was to compare effectiveness of the Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST) and electrophysiological evaluation in confirming diabetic peripheral neuropathy. One hundred twenty five known diabetes mellitus male and female subjects older than 18 with or without symptoms of neuropathy comprised in this research. All of them were interviewed in terms of demographic data, lipid profile, HbA1C, duration of disease, and history of retinopathy, so examined by Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST), and nerve conduction studies (NCS). The collected data were analyzed by SPSS software 18. One hundred twenty five diabetic patients (70 female, 55 male) were recruited in this study with a mean age of 58.7 ± 10.2, and mean duration of diabetes was 10.17 ± 6.9 years. The mean neuropathy score of MNSI and UKST were 2.3 (1.7) and 4.16 (2.9), respectively. Each instrument detected the peripheral neuropathy in 78 (69 %) and 91 (73 %) of patients, respectively. There was a significant relationship between number of neuropathies and mean of diabetes duration and development of retinopathy in both questionnaire evaluations and NCS. By nerve conduction study, neuropathy was detected in 121 (97 %) diabetic patients were reported in order 15 (12 %) mononeuropathy (as 33 % sensory and 67 % motor neuropathy) and 106 (85 %) polyneuropathy (as 31 % motor and 69 % sensorimotor neuropathy). As regards NCS is an objective, simple, and non-invasive tool and also can determine level of damage and regeneration in peripheral nerves, this study White, Claire M; van Doorn, Pieter A; Garssen, Marcel P J; Stockley, Rachel C Persistent feelings of fatigue (or subjective fatigue), which may be experienced in the absence of physiological factors, affect many people with peripheral neuropathy. A variety of interventions for subjective fatigue are available, but little is known about their efficacy or the likelihood of any adverse effects for people with peripheral neuropathy. To assess the effects of drugs and physical, psychological or behavioural interventions for fatigue in adults or children with peripheral neuropathy. On 5 November 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, CINAHL Plus, LILACS and AMED. We also searched reference lists of all studies identified for inclusion and relevant reviews, and contacted the authors of included studies and known experts in the field to identify additional published or unpublished data. We also searched trials registries for ongoing studies. We considered for inclusion randomised controlled trials (RCTs) and quasi-RCTs comparing any form of intervention for fatigue management in adults with peripheral neuropathy with placebo, no intervention or an alternative form of intervention for fatigue. Interventions considered included drugs, pacing and grading of physical activity, general or specific exercise, compensatory strategies such as orthotics, relaxation, counselling, cognitive and educational strategies. Two review authors independently assessed risk of bias and extracted study data. We contacted study authors for additional information. We collected information on adverse events from the included trials. The review includes three trials, which were all at low risk of bias, involving 530 people with peripheral neuropathy. The effects of amantadine from one randomised, double-blind, placebo-controlled, cross-over trial comparing amantadine with placebo for the treatment of fatigue in 80 people with Guillain-Barré syndrome (GBS) were uncertain for the proportion of people achieving Chekh, Viktor; Soliz, Peter; McGrew, Elizabeth; Barriga, Simon; Burge, Mark; Luan, Shuang Diabetic peripheral neuropathy (DPN) refers to the nerve damage that can occur in diabetes patients. It most often affects the extremities, such as the feet, and can lead to peripheral vascular disease, deformity, infection, ulceration, and even amputation. The key to managing diabetic foot is prevention and early detection. Unfortunately, current existing diagnostic techniques are mostly based on patient sensations and exhibit significant inter- and intra-observer differences. We have developed a computer aided diagnostic (CAD) system for diabetic peripheral neuropathy. The thermal response of the feet of diabetic patients following cold stimulus is captured using an infrared camera. The plantar foot in the images from a thermal video are segmented and registered for tracking points or specific regions. The temperature recovery of each point on the plantar foot is extracted using our bio-thermal model and analyzed. The regions that exhibit abnormal ability to recover are automatically identified to aid the physicians to recognize problematic areas. The key to our CAD system is the segmentation of infrared video. The main challenges for segmenting infrared video compared to normal digital video are (1) as the foot warms up, it also warms up the surrounding, creating an ever changing contrast; and (2) there may be significant motion during imaging. To overcome this, a hybrid segmentation algorithm was developed based on a number of techniques such as continuous max-flow, model based segmentation, shape preservation, convex hull, and temperature normalization. Verifications of the automatic segmentation and registration using manual segmentation and markers show good agreement. Tariman, Joseph D; Love, Ginger; McCullagh, Emily; Sandifer, Stacey The novel therapies thalidomide and bortezomib can cause peripheral neuropathy, a challenging adverse event that can affect quality of life and compromise optimal treatment for patients with multiple myeloma. At baseline, patients should be evaluated for signs and symptoms of peripheral neuropathy with a neurotoxicity assessment tool and educated about the symptoms and the importance of reporting them. Signs, symptoms, and the ability to perform activities of daily living should be evaluated regularly so that appropriate interventions can be employed if necessary. Specific management strategies for peripheral neuropathy are based on the grade of severity and on signs and symptoms; strategies include dose and schedule modifications, pharmacologic interventions, nonpharmacologic approaches, and patient education. Menezes, Manoj P; Ouvrier, Robert A Mitochondrial diseases in children are often associated with a peripheral neuropathy but the presence of the neuropathy is under-recognized because of the overwhelming involvement of the central nervous system (CNS). These mitochondrial neuropathies are heterogeneous in their clinical, neurophysiological, and histopathological characteristics. In this article, we provide a comprehensive review of childhood mitochondrial neuropathy. Early recognition of neuropathy may help with the identification of the mitochondrial syndrome. While it is not definite that the characteristics of the neuropathy would help in directing genetic testing without the requirement for invasive skin, muscle or liver biopsies, there appears to be some evidence for this hypothesis in Leigh syndrome, in which nuclear SURF1 mutations cause a demyelinating neuropathy and mitochondrial DNA MTATP6 mutations cause an axonal neuropathy. POLG1 mutations, especially when associated with late-onset phenotypes, appear to cause a predominantly sensory neuropathy with prominent ataxia. The identification of the peripheral neuropathy also helps to target genetic testing in the mitochondrial optic neuropathies. Although often subclinical, the peripheral neuropathy may occasionally be symptomatic and cause significant disability. Where it is symptomatic, recognition of the neuropathy will help the early institution of rehabilitative therapy. We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease. Tanishima, Hiroyuki; Tominaga, Toshiji; Kimura, Masamichi; Maeda, Tsunehiro; Shirai, Yasutsugu; Horiuchi, Tetsuya Chronic peripheral neuropathy is a major adverse response to oxaliplatin-containing chemotherapy regimens, but there are no established risk factors pertaining to it. We investigated the efficacy of hyperacute peripheral neuropathy (HAPN) as a predictor of oxaliplatin-induced persistent peripheral neuropathy (PPN). Forty-seven cases of stage III colorectal cancer who received adjuvant chemotherapy with oxaliplatin after curative surgery between January 2010 and August 2014 were retrospectively reviewed. HAPN was defined as acute peripheral neuropathy (APN) occurring on day 1 (≤24 h after oxaliplatin infusion) of the first cycle. PPN was defined as neuropathy lasting >1 year after oxaliplatin discontinuation. The average total dose of oxaliplatin was 625.8 mg/m(2), and the average relative dose intensity was 66.7%. Twenty-two of the 47 patients (46.8%) had PPN and 13 (27.7%) had HAPN. Male sex, treatment for neuropathy, HAPN, and APN were significantly more frequent in patients with PPN (p = 0.013, 0.02, <0.001, and 0.023, respectively). There was no significant difference in the total oxaliplatin dose between patients with and without PPN (p = 0.061). Multivariate analyses revealed total dose of oxaliplatin and HAPN as independent predictors of PPN [p = 0.015; odds ratio (OR) = 1.005, 95% confidence interval (CI), 1.001-1.009 and p = 0.001; OR = 75.307, 5.3-1070.123, respectively]. The total dose of oxaliplatin was relatively lower in patients with HAPN than that in those without HAPN in the PPN-positive group (not significant, p = 0.068). HAPN was found to be a predictor of oxaliplatin-induced PPN. Peripheral neuropathy is associated with major morbidity in the diabetic population. The detection of whether peripheral neuropathy is simply present or not in patients with diabetes is insufficient. What is required is a reliable measure of both the extent and severity of neuropathy, as this enables the appropriate allocation of resources and improves the quality of care for the patients who need it most. Standardized approaches involving the use of a neurothesiometer and a 10 g monofilament can provide a reliable and objective measure of the extent and severity of neuropathy, and should therefore be adopted into protocols for best practice in the assessment of neuropathy. Zheng, Huaien; Xiao, Wen Hua; Bennett, Gary J Cancer chemotherapeutics like paclitaxel and oxaliplatin produce a dose-limiting chronic sensory peripheral neuropathy that is often accompanied by neuropathic pain. The cause of the neuropathy and pain is unknown. In animal models, paclitaxel-evoked and oxaliplatin-evoked painful peripheral neuropathies are accompanied by an increase in the incidence of swollen and vacuolated mitochondria in peripheral nerve axons. It has been proposed that mitochondrial swelling and vacuolation are indicative of a functional impairment and that this results in a chronic axonal energy deficiency that is the cause of the neuropathy's symptoms. However, the significance of mitochondrial swelling and vacuolation is ambiguous and a test of the hypothesis requires a direct assessment of the effects of chemotherapy on mitochondrial function. The results of such an assessment are reported here. Mitochondrial respiration and ATP production were measured in rat sciatic nerve samples taken 1-2 days after and 3-4 weeks after induction of painful peripheral neuropathy with paclitaxel and oxaliplatin. Significant deficits in Complex I-mediated and Complex II-mediated respiration and significant deficits in ATP production were found for both drugs at both time points. In addition, prophylactic treatment with acetyl-l-carnitine, which inhibited the development of paclitaxel-evoked and oxaliplatin-evoked neuropathy, prevented the deficits in mitochondrial function. These results implicate mitotoxicity as a possible cause of chemotherapy-evoked chronic sensory peripheral neuropathy. Ten Hoope, Werner; Looije, Marjolein; Lirk, Philipp The aim of this review is to summarize recent relevant literature regarding regional anesthesia in the diabetic neuropathic patient and formulate recommendations for clinical practice. Diabetic neuropathic nerves, but not nerves of diabetic patients per se, exhibit complex functional changes. As a result, they seem more sensitive to local anesthetics, and are more difficult to stimulate. When catheters are used postoperatively, diabetes is an independent risk factor for infection. The pathophysiologic mechanisms underlying diabetic polyneuropathy are complex. Several pathways are thought to contribute to the development of diabetic neuropathy, triggered most importantly by chronic hyperglycemia. The latter induces inflammation and oxidative stress, causing microvascular changes, local ischemia and decreased axonal conduction velocity. Regional anesthesia is different in patients with diabetic neuropathy in several regards. First, the electric stimulation threshold of the nerve is markedly increased whereby the risk for needle trauma in stimulator-guided nerve blocks is theoretically elevated. Second, the diabetic nerve is more sensitive to local anesthetics, which results in longer block duration. Third, local anesthetics have been conjectured to be more toxic in diabetic neuropathy but the evidence is equivocal and should not be a cause to deny regional anesthesia to patients with a valid indication. Lastly, when peripheral nerve catheters are used, diabetes is an independent predisposing factor for infection. Cassereau, J; Codron, P; Funalot, B Mitochondrial disorders (MIDs) are frequently responsible for neuropathies with variable severity. Mitochondrial diseases causing peripheral neuropathies (PNP) may be due to mutations of mitochondrial DNA (mtDNA), as is the case in MERRF and MELAS syndromes, or to mutations of nuclear genes. Secondary abnormalities of mtDNA (such as multiple deletions of muscle mtDNA) may result from mitochondrial disorders due to mutations in nuclear genes involved in mtDNA maintenance. This is the case in several syndromes caused by impaired mtDNA maintenance, such as Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO) due to recessive mutations in the POLG gene, which encodes the catalytic subunit of mtDNA polymerase (DNA polymerase gamma), or Mitochondrial Neuro-Gastro-Intestinal Encephalomyopathy (MNGIE), due to recessive mutations in the TYMP gene, which encodes thymidine phosphorylase. The last years have seen a growing list of evidence demonstrating that mitochondrial bioenergetics and dynamics might be dysfunctional in axonal Charcot-Marie-Tooth disease (CMT2), and these mechanisms might present a common link between dissimilar CMT2-causing genes. Copyright © 2014 Elsevier Masson SAS. All rights reserved. Höliner, Isabella; Haslinger, Vera; Lütschg, Jürg; Müller, Guido; Barbarini, Daniela Seick; Fussenegger, Jörg; Zanier, Ulrike; Saely, Christoph H; Drexel, Heinz; Simma, Burkhard The aim of this study was to evaluate the prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus and examine whether the neurological examination validly diagnoses diabetic peripheral neuropathy as compared with the gold standard of nerve conduction velocity in these patients. Nerve conduction velocity was measured in an unselected consecutive series of patients aged 8-18 years who had been suffering from type 1 diabetes mellitus for at least 1 year. For the neurological examination, neuropathy disability scores and neuropathy sign scores were used. Of the 39 patients, six (15%) had clinically evident diabetic peripheral neuropathy, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 15 (38%) patients. Sensitivity and specificity of the neurological examination for the diagnosis of diabetic peripheral neuropathy were 40% and 100%, respectively. The corresponding positive and negative predictive values were 100% and 72.7%, respectively. This conclusions from this study are that in children and adolescents with type 1 diabetes mellitus, diabetic peripheral neuropathy is highly prevalent, but in the majority of patients it is subclinical. Sensitivity and negative predictive values of the neurological examination are low. Therefore, routine nerve conduction velocity measurement for the assessment of diabetic peripheral neuropathy appears to be warranted in these patients. Zaroulis, Chrysothea K; Chairopoulos, Konstantinos; Sachanas, Sotirios P; Maltezas, Dimitris; Tzenou, Tatiana; Pessach, Ilias; Koulieris, Efstathios; Koutra, Eleni; Kilindireas, Konstantinos; Pangalis, Gerasimos A; Kyrtsonis, Marie-Christine We evaluated bortezomib induced peripheral neuropathy (BIPN) characteristics in an attempt to better clarify the type, grade, duration and reversibility of neuropathy as well as investigate possible peripheral neuropathy (PN) risk factors and detect the best way to manage it. We calculated the grading of neuropathy using the Total Neuropathy Score reduced version (TNSr) in a series of 51 patients with relapsed/refractory multiple myeloma treated with bortezomib. Seventy percent developed clinical PN. BIPN, although manageable, is frequently underestimated in patients treated with bortezomib intravenously. Continuous follow-up and management of PN are needed to avoid quality of life impairment. Carson, Cindy Alberts Introduction Tart cherries have a long history as a treatment for gout and joint pain. While the exact mechanism of action is unknown, it is believed that acanthocyanin pigments and related bioflavonoids found in tart cherries and other red fruits scavenge free radicals, modulate cytokines, reduce DNA degradation, decrease capillary permeability, inhibit cyclooxygenase, and strengthen biological membranes. Many of these biochemical reactions would be expected to reduce inflammation, pain, and edema. Significance of Study Peripheral polyneuropathies are common and are believed to affect up to 9% of the US population older than 50 y. These neuropathies may develop from direct compression of peripheral nerves, toxic or metabolic injury to nerve tissue, autoimmune attack, or nutritional deficiency. No cause is identified in approximately 30% of patients. The pathophysiology of polyneuropathies is complex and not fully understood, but 3 common patterns of damage occur: (1) distal axonopathy, where the cell bodies remain intact, but axons degenerate from distal to proximal, usually as the result of toxic or metabolic injury; (2) demyelination neuropathy, where damage to the myelin sheath from autoimmune, infectious, or other causes disrupts electrical signaling; and (3) ganglionopathies, where damage occurs at the cell body or neuron, a relatively rare occurrence. While weakness and loss of sensation are common in many peripheral polyneuropathies, “gain of function” symptoms, such as paresthesias and allodynia, are the most distressing and are very difficult to treat. It is believed that these symptoms are caused by alterations in ion channels, alterations in neurotransmitters and their receptors, and altered gene expression. Common conventional treatments include antiepileptics, antidepressants, NSAIDs, and narcotics. These medications alter ion channels and neurotransmitters, decrease the sensitivity of nociceptive receptors, and desensitize C fibers. Most patients Gewandter, Jennifer S; Freeman, Roy; Kitt, Rachel A; Cavaletti, Guido; Gauthier, Lynn R; McDermott, Michael P; Mohile, Nimish A; Mohlie, Supriya G; Smith, A Gordon; Tejani, Mohamedtaki A; Turk, Dennis C; Dworkin, Robert H To assess the design characteristics and reporting quality of published randomized controlled trials (RCTs) for treatments of chemotherapy-induced peripheral neuropathy (CIPN) initiated before or during chemotherapy. In this systematic review of RCTs of preventive or symptomatic pharmacologic treatments for CIPN initiated before or during chemotherapy treatment, articles were identified by updating the PubMed search utilized in the CIPN treatment guidelines published in the Journal of Clinical Oncology in 2014. Thirty-eight articles were identified. The majority included only patients receiving platinum therapies (61%) and used a placebo control (79%). Common exclusion criteria were preexisting neuropathy (84%), diabetes (55%), and receiving treatments that could potentially improve neuropathy symptoms (45%). Ninety-five percent of studies initiated the experimental treatment before CIPN symptoms occurred. Although 58% of articles identified a primary outcome measure (POM), only 32% specified a primary analysis. Approximately half (54%) of the POMs were patient-reported outcome measures of symptoms and functional impairment. Other POMs included composite measures of symptoms and clinician-rated signs (23%) and vibration tests (14%). Only 32% of articles indicated how data from participants who prematurely discontinued chemotherapy were analyzed, and 21% and 29% reported the number of participants who discontinued chemotherapy due to neuropathy or other/unspecified reasons, respectively. These data identify reporting practices that could be improved in order to enhance readers' ability to critically evaluate RCTs of CIPN treatments and use the findings to inform the design of future studies and clinical practice. Reporting recommendations are provided. © 2017 American Academy of Neurology. Al-Zuhairy, Ali; Schrøder, Henrik Daa; Plesner, Torben; Abildgaard, Niels; Sindrup, Søren H For several decades an association between MGUS, IgM-MGUS in particular, and peripheral neuropathy has been suspected. Several histopathology studies have shown binding of IgM to myelin and a secondary widening of myelin lamellae in cutaneous nerves and in the sural nerve of patients with IgM-MGUS, or Waldenström's Macroglobulinaemia (WM), and peripheral neuropathy. In this retrospective study we investigated the value of skin biopsy examination in the diagnosis of MGUS- and WM-associated peripheral neuropathy. A total of 117 patients, who were examined for an M-component in serum with associated nerve symptoms, had a skin biopsy taken and examined for immunoglobulin deposition in cutaneous nerves. Thirty-five patients were diagnosed with MGUS or WM and peripheral neuropathy with no other cause of neuropathy. Nineteen patients had MGUS but no peripheral neuropathy. Of the 35 patients with MGUS or WM and peripheral neuropathy, four had immunoglobulin deposition in the skin biopsy, all of whom had an IgM gammopathy. In the control group of 19 without peripheral neuropathy, three had immunoglobulin deposition in the skin biopsy, all of whom had IgM-MGUS. In both groups, there was a trend towards higher IgM blood levels in patients with immunoglobulin deposition. Half of the patients with IgM gammopathy in the neuropathy group had anti-MAG reactivity, whereas only one in the control group had weak anti-MAG reactivity. Our study indicates that examination of skin biopsies for immunoglobulin deposition does not add significant diagnostic value in the evaluation of neuropathies suspected to be caused by MGUS or WM. IgM immunoglobulin deposition in skin biopsy might merely be an epiphenomenon secondary to high IgM blood levels. Copyright © 2014 Elsevier B.V. All rights reserved. It usually starts in the hands and/or feet and creeps up the arms and legs. Sometimes it feels like a tingling or numbness. Other times, it’s more of a shooting and/or burning pain or sensitivity to temperature. It can include sharp, stabbing pain, and it can make it difficult to perform normal day-to-day tasks like buttoning a shirt, sorting coins in a purse, or walking. An estimated 30 to 40 percent of cancer patients treated with chemotherapy experience these symptoms, a condition called chemotherapy-induced peripheral neuropathy (CIPN). \| Cheng, Yiling J; Gregg, Edward W; Kahn, Henry S; Williams, Desmond E; De Rekeneire, Nathalie; Narayan, K M Venkat The relation between height and lower extremity peripheral insensate neuropathy among persons with and without diabetes was examined by use of the 1999-2002 US National Health and Nutrition Examination Survey with 5,229 subjects aged 40 or more years. A monofilament was used to determine whether any of three areas on each foot were insensate. Peripheral insensate neuropathy was defined as the presence of one or more insensate areas. Its prevalence was nearly twice as high among persons with diabetes (21.2%) as among those without diabetes (11.5%; p < 0.001). Men (16.2%) had 1.7 times the prevalence of peripheral insensate neuropathy as did women (9.4%), but the difference was not significant after adjustment for height. Greater height was associated with increased peripheral insensate neuropathy prevalence among persons with and without diabetes (p < 0.001). This association was characterized by a sharp increase in prevalence among persons who were taller than 175.5 cm. Peripheral insensate neuropathy risk was significantly higher among those taller than 175.5 cm (adjusted odds ratio = 2.3, 95% confidence interval: 1.5, 3.5). The authors conclude that body height is an important correlate of peripheral insensate neuropathy. This association largely accounts for the difference in peripheral insensate neuropathy prevalence between men and women. Height may help health-care providers to identify persons at high risk of peripheral insensate neuropathy. Snyder, Matthew J; Gibbs, Lawrence M; Lindsay, Tammy J Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects quality of life. It typically causes burning pain, paresthesias, and numbness in a stocking-glove pattern that progresses proximally from the feet and hands. Clinicians should carefully consider the patient's goals and functional status and potential adverse effects of medication when choosing a treatment for painful diabetic peripheral neuropathy. Pregabalin and duloxetine are the only medications approved by the U.S. Food and Drug Administration for treating this disorder. Based on current practice guidelines, these medications, with gabapentin and amitriptyline, should be considered for the initial treatment. Second-line therapy includes opioid-like medications (tramadol and tapentadol), venlafaxine, desvenlafaxine, and topical agents (lidocaine patches and capsaicin cream). Isosorbide dinitrate spray and transcutaneous electrical nerve stimulation may provide relief in some patients and can be considered at any point during therapy. Opioids and selective serotonin reuptake inhibitors are optional third-line medications. Acupuncture, traditional Chinese medicine, alpha lipoic acid, acetyl-l-carnitine, primrose oil, and electromagnetic field application lack high-quality evidence to support their use. Sridhar, A V; Gosalakkal, J; Pye, I F; Houtman, P Peripheral neuropathy is an uncommon complication in paediatric systemic lupus erythematosus (SLE). We report the case of a 10-year-old Chinese girl who developed peripheral neuropathy within 3 months of the onset of SLE and presented with bilateral foot drop and sensory symptoms of both hands and feet. There was no involvement of the central nervous system at the time of presentation. The patient was negative for anticardiolipin antibodies, but positive for lupus anticoagulant. She was treated with intravenous methylprednisolone followed by oral steroids, methotrexate, gabapentin and amitryptyline. Although peripheral neuropathy is a rare complication of paediatric systemic lupus erythematosus, one should be vigilant for this entity as part of the neurological spectrum. It may not be associated with involvement of the central nervous system. Antiphospholipid antibodies may have role in the pathogenesis of SLE associated peripheral neuropathy. We speculate that routine nerve conduction studies may have a role in detecting sub-clinical cases. Nicholas, P K; Voss, J G; Corless, I B; Lindgren, T G; Wantland, D J; Kemppainen, J K; Canaval, G E; Sefcik, E F; Nokes, K M; Bain, C A; Kirksey, K M; Eller, L S; Dole, P J; Hamilton, M J; Coleman, C L; Holzemer, W L; Reynolds, N R; Portillo, C J; Bunch, E H; Tsai, Y-F; Mendez, M R; Davis, S M; Gallagher, D M The prevalence of peripheral neuropathy is frequent in HIV disease and is often associated with antiretroviral therapy. Unhealthy behaviours, particularly substance-use behaviours, are utilized by many HIV-positive individuals to manage neuropathic symptoms. As part of a larger study on self-care for symptoms in HIV disease, this study analyzed the prevalence and characteristics of unhealthy behaviours to self-manage peripheral neuropathy in HIV disease. Sociodemographic and disease-related correlates and unhealthy behaviours were examined in a convenience sample of 1,217 respondents who were recruited from data collection sites in several US cities, Puerto Rico, Colombia, and Taiwan. Results of the study indicated that respondents with peripheral neuropathy (n=450) identified a variety of unhealthy self-care behaviours including injection drug use, oral drug use, smoking cigarettes and alcohol ingestion. Specific unhealthy behaviours that participants reported to alleviate peripheral neuropathy included use of marijuana (n=67), smoking cigarettes (n=139), drinking alcohol (n=81) and street drugs (n=30). A subset of those individuals (n=160), who identified high levels of neuropathy (greater than five on a scale of 1-10), indicated significantly higher use of amphetamines and injection drug use in addition to alcohol use and cigarette smoking. For participants from Norway, substance use (using alcohol: 56%) was one of the most frequent self-management strategies. Implications for clinical practice include assessment and education of persons with HIV for self-care management of the complex symptom of peripheral neuropathy. Cashman, Christopher R.; Höke, Ahmet Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wlds) and Sarmknockout animal models. These studies have shown axonal degeneration to occur througha programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration. PMID:25617478 Peters, Remco P H; Van Ramshorst, Mette S; Struthers, Helen E; McIntyre, James A Peripheral neuropathy is a well-known side effect of antiretroviral therapy (ART) in adult patients and is particularly related to the use of nucleoside reverse transcriptase inhibitors. This class of drugs is included in all first-line paediatric ART regimens in Africa, but data on the prevalence of neuropathy in children are scarce. In this cross-sectional study, 182 HIV-infected children on ART in rural South Africa were assessed for peripheral neuropathy using the neuropathy symptom score (NSS) and neuropathy disability score (NDS). Peripheral neuropathy was defined as NSS ≥ 5 or NDS ≥ 3. Neurological assessment was completed for 174 children (96 %). Symptoms of neuropathy were reported in NSS by 48 children (28 %; 95 % confidence interval (CI) 21-34 %), and signs were observed in NDS in 25 children (14 %; 95 % CI 12-16 %). A diagnosis of peripheral neuropathy was established in 42 children (24 %; 95 % CI 18-30 %). Independent risk factors for peripheral neuropathy were co-trimoxazole prophylaxis (adjusted odds ratio 0.45; 95 % CI 0.21-0.95, p = 0.036) and didanosine use (adjusted odds ratio 12; 95 % CI 1.3-116, p = 0.030). Peripheral neuropathy as determined by clinical assessment is a common condition in African children on ART. This review attempts to explain the symptoms experienced by patients with inflammatory neuropathies by pathophysiological events. The emphasis is not on the primary events that may cause a particular illness but on downstream events taking place in peripheral nerves or muscles. Symptoms that will be discussed include sensory predominance, motor predominance, activity-induced weakness, heat paresis, and cold paresis. Each symptom is associated with, but not limited to, particular neuropathies. Singh, Akanksha; Asif, Naiyer; Singh, Paras Nath; Hossain, Mohd Mobarak The post-menopausal phase is characterized by a decline in the serum oestrogen and progesterone levels. This phase is also associated with higher incidence of peripheral neuropathy. To explore the relationship between the peripheral motor nerve status and serum oestrogen and progesterone levels through assessment of Motor Nerve Conduction Velocity (MNCV) in post-menopausal women with peripheral neuropathy. This cross-sectional study was conducted at Jawaharlal Nehru Medical College during 2011-2013. The study included 30 post-menopausal women with peripheral neuropathy (age: 51.4±7.9) and 30 post-menopausal women without peripheral neuropathy (control) (age: 52.5±4.9). They were compared for MNCV in median, ulnar and common peroneal nerves and serum levels of oestrogen and progesterone estimated through enzyme immunoassays. To study the relationship between hormone levels and MNCV, a stepwise linear regression analysis was done. The post-menopausal women with peripheral neuropathy had significantly lower MNCV and serum oestrogen and progesterone levels as compared to control subjects. Stepwise linear regression analysis showed oestrogen with main effect on MNCV. The findings of the present study suggest that while the post-menopausal age group is at a greater risk of peripheral neuropathy, it is the decline in the serum estrogen levels which is critical in the development of peripheral neuropathy. Areti, Aparna; Yerra, Veera Ganesh; Komirishetty, Prashanth; Kumar, Ashutosh Background: Peripheral neuropathies are a group of diseases characterized by malfunctioning of peripheral nervous system. Neuropathic pain, one of the core manifestations of peripheral neuropathy remains as the most severe disabling condition affecting the social and daily routine life of patients suffering from peripheral neuropathy. Method: The current review is aimed at unfolding the possible role of mitochondrial dysfunction in peripheral nerve damage and to discuss on the probable therapeutic strategies against neuronal mitotoxicity. The article also highlights the therapeutic significance of maintaining a healthy mitochondrial environment in neuronal cells via pharmacological management in context of peripheral neuropathies. Results: Aberrant cellular signaling coupled with changes in neurotransmission, peripheral and central sensitization are found to be responsible for the pathogenesis of variant toxic neuropathies. Current research reports have indicated the possible involvement of mitochondria mediated redox imbalance as one of the principal causes of neuropathy aetiologies. In addition to imbalance in redox homeostasis, mitochondrial dysfunction is also responsible for alterations in physiological bioenergetic metabolism, apoptosis and autophagy pathways. Conclusions: In spite of various etiological factors, mitochondrial dysfunction has been found to be a major pathomechanism underlying the neuronal dysfunction associated with peripheral neuropathies. Pharmacological modulation of mitochondria either directly or indirectly is expected to yield therapeutic relief from various primary and secondary mitochondrial diseases. PMID:26818748 Asif, Naiyer; Singh, Paras Nath; Hossain, Mohd Mobarak Introduction The post-menopausal phase is characterized by a decline in the serum oestrogen and progesterone levels. This phase is also associated with higher incidence of peripheral neuropathy. Aim To explore the relationship between the peripheral motor nerve status and serum oestrogen and progesterone levels through assessment of Motor Nerve Conduction Velocity (MNCV) in post-menopausal women with peripheral neuropathy. Materials and Methods This cross-sectional study was conducted at Jawaharlal Nehru Medical College during 2011-2013. The study included 30 post-menopausal women with peripheral neuropathy (age: 51.4±7.9) and 30 post-menopausal women without peripheral neuropathy (control) (age: 52.5±4.9). They were compared for MNCV in median, ulnar and common peroneal nerves and serum levels of oestrogen and progesterone estimated through enzyme immunoassays. To study the relationship between hormone levels and MNCV, a stepwise linear regression analysis was done. Results The post-menopausal women with peripheral neuropathy had significantly lower MNCV and serum oestrogen and progesterone levels as compared to control subjects. Stepwise linear regression analysis showed oestrogen with main effect on MNCV. Conclusion The findings of the present study suggest that while the post-menopausal age group is at a greater risk of peripheral neuropathy, it is the decline in the serum estrogen levels which is critical in the development of peripheral neuropathy. PMID:28208850 Areti, Aparna; Yerra, Veera Ganesh; Komirishetty, Prashanth; Kumar, Ashutosh Peripheral neuropathies are a group of diseases characterized by malfunctioning of peripheral nervous system. Neuropathic pain, one of the core manifestations of peripheral neuropathy remains as the most severe disabling condition affecting the social and daily routine life of patients suffering from peripheral neuropathy. The current review is aimed at unfolding the possible role of mitochondrial dysfunction in peripheral nerve damage and to discuss on the probable therapeutic strategies against neuronal mitotoxicity. The article also highlights the therapeutic significance of maintaining a healthy mitochondrial environment in neuronal cells via pharmacological management in context of peripheral neuropathies. Aberrant cellular signaling coupled with changes in neurotransmission, peripheral and central sensitization are found to be responsible for the pathogenesis of variant toxic neuropathies. Current research reports have indicated the possible involvement of mitochondria mediated redox imbalance as one of the principal causes of neuropathy aetiologies. In addition to imbalance in redox homeostasis, mitochondrial dysfunction is also responsible for alterations in physiological bioenergetic metabolism, apoptosis and autophagy pathways. In spite of various etiological factors, mitochondrial dysfunction has been found to be a major pathomechanism underlying the neuronal dysfunction associated with peripheral neuropathies. Pharmacological modulation of mitochondria either directly or indirectly is expected to yield therapeutic relief from various primary and secondary mitochondrial diseases. Takenaka, Motoyasu; Iida, Hiroki; Matsumoto, Shigemi; Yamaguchi, Shinobu; Yoshimura, Noritaka; Miyamoto, Maki Although paclitaxel is a commonly used anticancer drug, peripheral neuropathy may develop as a side effect. Worsening of the symptoms with time may cause patients who receive paclitaxel to give up their chemotherapy. Duloxetine, a serotonin- and norepinephrine-reuptake inhibitor, has been used to treat peripheral neuropathic pain. We report the case of a 68-year-old man with gastric cancer, who underwent gastrectomy and then received 8 cycles of chemotherapy involving weekly administrations of paclitaxel. Under this paclitaxel treatment, he complained of severe peripheral neuropathy, leading to a diminished quality of life. Following treatment with a combination of duloxetine and pregabalin, a remission of his symptoms was achieved. Duloxetine plus pregabalin therapy may be useful for the peripheral neuropathy induced by paclitaxel. Peripheral neuropathy is a common adverse effect of paclitaxel and oxaliplatin treatment. The major dose-limiting side effect of these drugs is peripheral sensory neuropathy. The symptoms of paclitaxel-induced neuropathy are mostly sensory and peripheral in nature, consisting of mechanical allodynia/hyperalgesia, tingling, and numbness. Oxaliplatin-induced neurotoxicity manifests as rapid-onset neuropathic symptoms that are exacerbated by cold exposure and as chronic neuropathy that develops after several treatment cycles. Although many basic and clinical researchers have studied anticancer drug-induced peripheral neuropathy, the mechanism is not well understood. In this review, we focus on (1) analysis of transient receptor potential vanilloid 1 (TRPV1) channel expression in the rat dorsal root ganglion (DRG) after paclitaxel treatment and (2) analysis of transient receptor potential ankyrin 1 (TRPA1) channel in the DRG after oxaliplatin treatment. This review describes that (1) paclitaxel-induced neuropathic pain may be the result of up-regulation of TRPV1 in small- and medium-diameter DRG neurons. In addition, paclitaxel treatment increases the release of substance P, but not calcitonin gene-related peptide, in the superficial layers of the spinal dorsal horn. (2) TRPA1 expression via activation of p38 mitogen-activated protein kinase in small-diameter DRG neurons, at least in part, contributes to the development of oxaliplatin-induced acute cold hyperalgesia. We suggest that TRPV1 or TRPA1 antagonists may be potential therapeutic lead compounds for treating anticancer drug-induced peripheral neuropathy. Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. PMID:25829955 Jain, Anuj; Kohli, Ashok; Sachan, Deepak Sandhoff's disease is a rare autosomal-recessive disorder of sphingolipid metabolism that results from a deficiency of lysosomal enzyme beta-hexosaminidase A and B. The resultant accumulation of GM2 gangliosides within both grey matter and the myelin sheath of white matter results in essential, severe neurodegeneration. We describe a 14-month-old boy with seizures and severe neurodegeneration. His diagnosis was confirmed by neuroimaging and enzyme assay. In addition to the classic features of Sandhoff's disease, the child's clinical features were suggestive of neuropathy as supported by nerve conduction studies indicating that the bilateral median, ulnar, and common peroneal nerves were affected. Peripheral nervous system involvement is not consistently observed in infantile Sandhoff's disease, prompting us to report this case. Copyright 2010 Elsevier Inc. All rights reserved. Saylor, Deanna; Nakigozi, Gertrude; Nakasujja, Noeline; Robertson, Kevin; Gray, Ronald H; Wawer, Maria J; Sacktor, Ned To determine the prevalence, risk factors, and functional impairment associated with peripheral neuropathy in a prospective cohort of adults in rural Uganda. Eight hundred participants (400 HIV- and 400 antiretroviral-naive HIV+) in the Rakai Community Cohort Study underwent detailed neurologic evaluations including assessment of neuropathy symptoms, functional measures (Patient Assessment of Own Functioning Inventory and Karnofsky Performance Status scores), and neurologic evaluation by a trained medical officer. Neuropathy was defined as ≥1 subjective symptom and ≥1 sign of neuropathy on examination. Neuropathy risk factors were assessed using log binomial regression. Fifty-three percent of participants were men, with a mean (SD) age of 35 (8) years. Neuropathy was present in 13% of the cohort and was more common in HIV+ vs HIV- participants (19% vs 7%, p < 0.001). Older age (relative risk [RR] 1.04, 95% confidence interval [CI] 1.02-1.06), female sex (RR 1.49, 95% CI 1.04-2.15), HIV infection (RR 2.82, 95% CI 1.86-4.28), tobacco use (RR 1.59, 95% CI 1.02-2.48), and prior neurotoxic medication use (RR 2.08, 95% CI 1.07-4.05) were significant predictors of neuropathy in the overall cohort. Only older age was associated with neuropathy risk in the HIV+ (RR 1.03, 95% CI 1.01-1.05) and HIV- (RR 1.06, 95% CI 1.02-1.10) cohorts. Neuropathy was associated with impaired functional status on multiple measures across all participant groups. Peripheral neuropathy is relatively common and associated with impaired functional status among adults in rural Uganda. Older age, female sex, and HIV infection significantly increase the risk of neuropathy. Neuropathy may be an underrecognized but important condition in rural Uganda and warrants further study. © 2017 American Academy of Neurology. Rao, Deepa B; Jortner, Bernard S; Sills, Robert C Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy--namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves. Sabanayagam, Charumathi; Tai, E Shyong; Lee, Jeannette; Lim, Su Chi; Wong, Tien Yin Retinal vascular caliber changes predict diabetic microvascular complications such as retinopathy, and nephropathy. However, the association between retinal vasculature and peripheral neuropathy is not well studied. We evaluated the association between retinal vascular caliber and peripheral neuropathy in a multi-ethnic Asian population with diabetes (n = 423) in Singapore. Retinal arteriolar and venular caliber was measured from digital retinal photographs and summarized as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent. Peripheral neuropathy was defined from neurothesiometer or monofilament sensory testing. Larger CRAE was positively associated with peripheral neuropathy independent of age, sex, ethnicity, current smoking, alcohol consumption, body mass index, total cholesterol, systolic blood pressure, and duration of diabetes. The multivariable odds ratio (OR) [95% confidence interval (CI)] of peripheral neuropathy was 2.81 (1.38-5.73) comparing highest vs. lower three quartiles of CRAE. This association was consistently present in analyses stratified by age, sex and ethnicity. Retinal venular caliber was not associated with peripheral neuropathy. These data suggest that larger retinal arteriolar diameters are associated with peripheral neuropathy independent of major risk factors. Hansberry, David R; Suresh, Ragha; Agarwal, Nitin; Heary, Robert F; Goldstein, Ira M Given its practicality, the internet is a primary resource for patients afflicted with diseases like peripheral neuropathy. Therefore, it is important that the readily available online resources on peripheral neuropathy are tailored to the general public, particularly concerning readability. Patient education resources were downloaded from the US National Library of Medicine, Mayo Clinic, National Institute of Neurological Disorders and Stroke, Neuropathy.org, GBS/CIDP Foundation International, Hereditary Neuropathy Foundation, Charcot-Marie-Tooth Association, Foundation for Peripheral Neuropathy, and Neuropathy Action Foundation websites. All patient education material related to peripheral neuropathy was evaluated for its level of readability using the Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level. The FRE scores averaged 43.4 with only the US National Library of Medicine scoring above 60 (76.5). The Flesch-Kincaid Grade Level scores averaged 11.0. All scores were above a seventh-grade level except the US National Library of Medicine, which had a score of a fifth-grade reading level. Most Americans may not fully benefit from patient education resources concerning peripheral neuropathy education on many of the websites. Only the US National Library of Medicine, which is written at a fifth-grade level, is likely to benefit the average American. Fu Liong, Hiew; Santhi, Datuk Puvanarajah; Shanthi, Viswanathan; Mohd Hanip, Rafia Background. Since 2008, we have observed an increasing number of Myanmarese refugees in Malaysia being admitted for acute/subacute onset peripheral neuropathy. Most of them had a preceding history of starvation. Methods. We retrospectively studied the clinical features of all Myanmarese patients admitted with peripheral neuropathy from September 2008 to January 2014. Results. A total of 24 patients from the Chin, Rohingya, and Rakhine ethnicities (mean age, 23.8 years; male, 96%) had symmetrical, ascending areflexic weakness with at least one additional presenting symptom of fever, lower limb swelling, vomiting, abdominal pain, or difficulty in breathing. Twenty (83.3%) had sensory symptoms. Ten (41.6%) had cranial nerve involvement. Nineteen patients had cerebrospinal fluid examinations but none with evidence of albuminocytological dissociation. Neurophysiological assessment revealed axonal polyneuropathy, predominantly a motor-sensory subtype. Folate and vitamin B12 deficiencies were detected in 31.5% of them. These findings suggested the presence of a polyneuropathy related to nutrition against a backdrop of other possible environmental factors such as infections, metabolic disorders, or exposure to unknown toxin. Supportive treatment with appropriate vitamins supplementation improved functional outcome in most patients. Conclusion. We report a spectrum of acquired reversible neurological manifestations among Myanmarese refugees likely to be multifactorial with micronutrient deficiencies playing an important role in the pathogenesis. Brewer, Jamie R; Morrison, Gladys; Dolan, M. Eileen; Fleming, Gini F As there are increasing numbers of cancer survivors, more attention is being paid to the long term unwanted effects patients may experience as a result of their treatment and the impact these side effects can have on their quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxicities from chemotherapy. In this review we will briefly review the clinical presentation, evaluation and management of chemotherapy-induced peripheral neuropathy, with a focus on CIPN related to platinum and taxane agents. We will then discuss current clinical models of peripheral neuropathy and ongoing research to better understand CIPN and develop potential treatment options. PMID:26556766 Martin, Catherine L.; Waberski, Barbara H.; Pop-Busui, Rodica; Cleary, Patricia A.; Catton, Sarah; Albers, James W.; Feldman, Eva L.; Herman, William H. OBJECTIVE To describe the sensitivity, specificity, positive predictive value, and negative predictive value of vibration perception threshold (VPT) testing in subjects with type 1 diabetes relative to gold standard assessments of peripheral neuropathy. RESEARCH DESIGN AND METHODS VPT was determined in 1,177 adults with type 1 diabetes 13–14 years after participating in a study of intensive (INT) versus conventional (CONV) diabetes treatment. Abnormal VPT was defined by values exceeding 2.5 SD above age-specific normal values. Signs and symptoms of peripheral neuropathy were assessed and electrodiagnostic studies were performed to establish definite clinical neuropathy, abnormal nerve conduction, and confirmed clinical neuropathy (the presence of both definite clinical neuropathy and abnormal nerve conduction). RESULTS Thirty-seven percent of subjects had definite clinical neuropathy, 61% had abnormal nerve conduction, and 30% had confirmed clinical neuropathy. Abnormal VPT was more common among former CONV than among INT subjects (64 vs. 57%, P < 0.05) and was associated with older age. VPT was a sensitive measure of confirmed clinical neuropathy (87%) and of definite clinical neuropathy (80%) and a specific measure of abnormal nerve conduction (62%). Higher VPT cut points improved test sensitivity and lower cut points improved specificity. Areas under the receiver operating characteristic curves ranged from 0.71–0.83 and were higher for older than for younger subjects and highest for those with confirmed clinical neuropathy. CONCLUSIONS VPT was a sensitive measure of peripheral neuropathy. Future researchers may choose to select VPT cut points for defining abnormality based on the population studied and clinical outcome of interest. PMID:20833868 In 2012, interest remains high in the field of dysimmune neuropathies, chiefly concerning Guillain-Barré syndrome (GBS). The pathophysiological mechanisms are now better known but electrophysiological criteria should be updated. The risk of GBS in H1N1 vaccination is now well evaluated. Nerve ultrasonography provides new prospects for diagnosis and follow-up of dysimmune neuropathies but cannot substitute for electrophysiology. This paper aims to present some noteworthy articles published in 2012 in the field of dysimmune neuropathies. Copyright © 2013 Elsevier Masson SAS. All rights reserved. García-Cabo, Carmen; Morís, Germán One of the most frequent neurologic complications reported in inflammatory bowel disease population is peripheral neuropathy; however, clinical aspects of peripheral nerve damage are not well characterized. The aim of the review is to present the existing literature on peripheral neuropathy in inflammatory bowel disease patients. A literature search identified the publications reporting on epidemiology, clinical features, underlying mechanisms and management of ulcerative colitis and Crohn's disease patients with peripheral nerve involvement. The pathogenesis of peripheral nervous system damage in inflammatory bowel disease has yet to be elucidated, although it seems to be related to immune mechanisms; therefore, treatment with immunotherapy is recommended. In addition, peripheral neuropathy may appear as iatrogenic-related disorders associated with several drugs used in controlling inflammatory bowel disease activity; finally, peripheral neuropathy may also be caused by micronutrient deficiencies secondary to malabsorption-related disorders. Although peripheral nervous nerve damage associated with inflammatory bowel disease is rarely reported, clinicians should be aware of the peripheral neuropathy clinical manifestations in order to recognize it and provide early treatment, which is crucial for preventing major neurologic morbidity. Heightened awareness is necessary for the successful management of these patients. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. Rao, Deepa B.; Jortner, Bernard S.; Sills, Robert C. Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy—namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves. PMID:24615445 Hammersla, Margaret; Kapustin, Jane Faith Peripheral neuropathy (PN) is a common and often progressive condition frequently seen in primary care. The chronic pain associated with PN, or neuropathic pain, can significantly diminish patients' quality of life and be challenging to treat. Mendoza, Tito R; Wang, Xin Shelley; Williams, Loretta A; Shi, Qiuling; Vichaya, Elisabeth G; Dougherty, Patrick M; Thomas, Sheeba K; Yucel, Emre; Bastida, Christel C; Woodruff, Jeanie F; Cleeland, Charles S Various sensory and motor effects are associated with cancer treatment-induced peripheral neuropathy. The current method for capturing the multifaceted nature of neuropathy includes a combination of objective tests, clinician evaluation, and subjective patient report, an approach that is often not logistically feasible, especially for multisite trials. We report the performance of a brief yet comprehensive, easily administered measure, the Treatment-Induced Neuropathy Assessment Scale (TNAS), for assessing the severity and course of neuropathy across various cancer treatments. Data were derived from 4 longitudinal or cross-sectional patient cohorts (N = 573). Patients with multiple myeloma treated primarily with bortezomib and patients with colorectal cancer receiving oxaliplatin evaluated candidate items. Cognitive debriefing showed that all items were easy to understand, and this preliminary TNAS demonstrated reliability, validity, and sensitivity. Numbness/tingling was the most severe item, regardless of therapeutic agent. Although numbness and general pain were moderately correlated, patients perceived them as distinct. Most TNAS items were more severe at follow-up, demonstrating the sensitivity of the instrument to accumulating dose. The TNAS will be refined with further patient input, with final psychometric evaluation conducted in a new patient sample receiving treatments known to be associated with peripheral neuropathy. The nonpainful component of neuropathy may be more disabling than the pain component. Our data suggest that the nonpainful components of neuropathy may be more disabling than the pain component during cancer treatment. Here we report data on sensory and motor symptoms reported by patients receiving neurotoxic cancer therapy, and we detail the development of a neuropathy assessment scale that follows regulatory guidance for patient-reported outcomes. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved. Peripheral neuropathy is a common long-term complication of diabetes mellitus. In many patients, neuropathy is accompanied by pain, which is often difficult to manage effectively. Drug treatment options include certain antidepressants and antiepileptic drugs. Another option is the use of topical capsaicin. In this article, we consider the evidence for capsaicin in the management of diabetic peripheral neuropathy and how it fits with current management strategies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ Syngle, Ashit; Verma, Inderjeet; Krishan, Pawan; Garg, Nidhi; Syngle, Vijaita Diabetic peripheral neuropathy and diabetic autonomic neuropathy are serious and common complications of diabetes associated with increased risk of mortality and cardiovascular disease. We sought to evaluate the safety and efficacy of minocycline in type 2 diabetic patients with diabetic peripheral and autonomic neuropathy. In a randomized placebo controlled study, 50 outpatients were randomly assigned to receive 100 mg minocycline or placebo. Outcome measures included the vibration perception threshold (VPT), Leeds assessment of neuropathic symptoms and signs (LANSS), Pain Disability Index (PDI), Visual Analog Scale (VAS), beck depression inventory (BDI), health assessment questionnaire (HAQ) and autonomic neuropathy, assessed by cardiovascular reflex tests according to Ewing and peripheral sympathetic autonomic function was assessed by FDA approved Sudoscan. At baseline there were no significant differences between demographic variables and the neuropathy variables in the minocycline and placebo groups. After treatment, VPT significantly improved in the minocycline group as compared to the placebo group. Mean posttreatment scores on the LANSS, PDI and HAQ were significantly lower in the minocycline group compared with the placebo group. However, BDI and VAS significantly (p = 0.01) improved in both minocycline and placebo groups (Table 2). After treatment with minocycline, heart rate (HR) response to standing significantly improved, while there was a borderline significance toward a reduction in HR response to deep breath. These finding indicate that 6-week oral treatment with minocycline is safe, well tolerated and significantly improves peripheral and autonomic neuropathy in type 2 diabetic patients. Salehi, Zeinab; Roayaei, Mahnaz Peripheral neuropathy is one of the most important limitations of oxaliplatin base regimen, which is the standard for the treatment of colorectal cancer. Evidence has shown that Vitamin E may be protective in chemotherapy-induced peripheral neuropathy. The aim of this study is to evaluate the effect of Vitamin E administration on prevention of oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer. This was a prospective randomized, controlled clinical trial. Patients with colorectal cancer and scheduled to receive oxaliplatin-based regimens were enrolled in this study. Enrolled patients were randomized into two groups. The first group received Vitamin E at a dose of 400 mg daily and the second group observed, until after the sixth course of the oxaliplatin regimen. For oxaliplatin-induced peripheral neuropathy assessment, we used the symptom experience diary questionnaire that completed at baseline and after the sixth course of chemotherapy. Only patients with a score of zero at baseline were eligible for this study. Thirty-two patients were randomized to the Vitamin E group and 33 to the control group. There was no difference in the mean peripheral neuropathy score changes (after - before) between two groups, after sixth course of the oxaliplatin base regimen (mean difference [after - before] of Vitamin E group = 6.37 ± 2.85, control group = 6.57 ± 2.94; P = 0.78). Peripheral neuropathy scores were significantly increased after intervention compared with a base line in each group (P < 0.001). The results from this current trial demonstrate a lack of benefit for Vitamin E in preventing oxaliplatin-induced peripheral neuropathy. Saltık, Sema; Türkeş, Muzaffer; Tüzün, Erdem; Cakır, Arif; Ulusoy, Canan Autoantibodies to glutamic acid decarboxylase are found in some rare neurological diseases. However, acute peripheral neuropathy associated with antiglutamic acid decarboxylase autoimmunity has not been reported previously. Here we report a case of a patient who presented with acute cranial and peripheral neuropathy in association with the presence of serum antiglutamic acid decarboxylase antibodies. A 13-year-old boy was admitted to our pediatric neurology clinic with diplopia due to sixth cranial nerve palsy and ascending motor weakness in all extremities. The nerve conduction studies showed bilateral motor and sensory demyelinating neuropathy. Full recovery was achieved following intravenous immunoglobulin treatment. Glutamic acid decarboxylase autoimmunity-associated neurological diseases spectrum may also include acute demyelinating peripheral neuropathy. Copyright © 2013 Elsevier Inc. All rights reserved. Zheng, H; Xiao, W H; Bennett, G J Many of the most effective anti-cancer drugs induce a dose-limiting peripheral neuropathy that compromises therapy. Evidence from animal models of chemotherapy-induced painful peripheral neuropathy produced by the taxane agent, paclitaxel, and the platinum-complex agent, oxaliplatin, indicate that they produce neuropathy via a common mechanism-a toxic effect on the mitochondria in primary afferent sensory neurons. Bortezomib is from the proteasome-inhibitor class of chemotherapeutics. It also produces a dose-limiting peripheral neuropathy, but its effects on neuronal mitochondria are unknown. To investigate this, we developed a model of bortezomib-induced painful peripheral neuropathy in the rat and assessed mitochondrial function (respiration and ATP production) in sciatic nerve samples harvested at two time points: day 7, which is three days after treatment and before pain appears, and day 35, which is one month post-treatment and the time of peak pain severity. We found significant deficits in Complex I-mediated and Complex II-mediated respiration, and in ATP production at both time points. Prophylactic treatment with acetyl-L-carnitine, which has previously been shown to prevent paclitaxel- and oxaliplatin-induced mitochondrial dysfunction and pain, completely blocked bortezomib's effects on mitochondria and pain. These results suggest that mitotoxicity may be the core pathology for all chemotherapy-induced peripheral neuropathy and that drugs that protect mitochondrial function may be useful chemotherapy adjuncts. Polycythemia vera is a rare myeloproliferative disease. Cutaneous symptoms are uncommon. We report about a 72-year-old female patient with JAK2(V617F) -positive polycythemia who developed peripheral sensorimotor axonal neuropathy and erythromelalgia. Possible causes and treatment are discussed. Diabetes is an increasing epidemic in Korea, and associated diabetic peripheral neuropathy (DPN) is its most common and disabling complication. DPN has an insidious onset and heterogeneous clinical manifestations, making it difficult to detect high-risk patients of DPN. Early diagnosis is recommended and is the key factor for a better prognosis and preventing diabetic foot ulcers, amputation, or disability. However, diagnostic tests for DPN are not clearly established because of the various pathophysiology developing from the nerve injury to clinical manifestations, differences in mechanisms according to the type of diabetes, comorbidities, and the unclear natural history of DPN. Therefore, DPN remains a challenge for physicians to screen, diagnose, follow up, and evaluate for treatment response. In this review, diagnosing DPN using various methods to assess clinical symptoms and/or signs, sensorineural impairment, and nerve conduction studies will be discussed. Clinicians should rely on established modalities and utilize current available testing as complementary to specific clinical situations. PMID:27246283 Allen, David C; Smallman, Clare A; Mills, Kerry R A man with multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), or Lewis-Sumner syndrome, presented with a progressive left lumbosacral plexus lesion resembling a neurofibroma. After 7 years he developed a left ulnar nerve lesion with conduction block in its upper segment. Treatment with intravenous immunoglobulin improved the symptoms and signs of both lesions. We conclude that inflammatory neuropathy must be considered in the differential diagnosis of peripheral nerve tumors, and that unifocal lesions may precede multifocal involvement in MADSAM by several years. In addition, we discuss the clinical features in 9 patients attending a specialist peripheral nerve clinic and review the literature. Stino, Amro M; Smith, Albert G Peripheral neuropathy is a major cause of disability worldwide. Diabetes is the most common cause of neuropathy, accounting for 50% of cases. Over half of people with diabetes develop neuropathy, and diabetic peripheral neuropathy (DPN) is a major cause of reduced quality of life due to pain, sensory loss, gait instability, fall-related injury, and foot ulceration and amputation. Most patients with non-diabetic neuropathy have cryptogenic sensory peripheral neuropathy (CSPN). A growing body of literature links prediabetes, obesity and metabolic syndrome to the risk of both DPN and CSPN. This association might be particularly strong in type 2 diabetes patients. There are no effective medical treatments for CSPN or DPN, and aggressive glycemic control is an effective approach to neuropathy risk reduction only in type 1 diabetes. Several studies suggest lifestyle-based treatments that integrate dietary counseling with exercise might be a promising therapeutic approach to early DPN in type 2 diabetes and CSPN associated with prediabetes, obesity and metabolic syndrome. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. Cavana, Paola; Sammartano, Federica; Capucchio, Maria T; Catalano, Deborah; Valazza, Alberto; Farca, Anna M A 12-year-old male cat was referred for progressive limb weakness lasting 2 weeks. Physical examination detected muscle atrophy and bilateral renomegaly with distortion of the renal contours. The cat was ambulatory but tetraparetic. It showed a peculiar posture on forelimbs with bilateral flexion of the carpi and extrarotation of forearms. The cat was unable to go upstairs or jump. Neurological examination showed findings compatible with peripheral nervous system involvement. Histopathological findings revealed a high grade non-B, non-T cell renal lymphoma and peripheral neuropathy characterised by demyelination, axonal degeneration and muscle denervation. In the absence of congenital, metabolic and infectious diseases or exposure to toxins, a paraneoplastic peripheral neuropathy was hypothesised. In humans and dogs, paraneoplastic peripheral neuropathies have been documented with different neoplastic processes including lymphoproliferative disorders. To the authors' knowledge, this is the first report of suspected paraneoplastic polyneuropathy in a cat with malignant tumour. Rusina, R; Keller, O; Síma, R; Zámečník, J Whipples disease is a chronic multisystem inflammatory disease with predominantly gastrointestinal manifestations due to Tropheryma whipplei infection. Typical neurological abnormalities include dementia, eye movement abnormalities, hypothalamic dysfunction and oculomasticatory myorhythmias. The literature on peripheral neuropathy in Whipples disease is sparse and the involvement of peripheral nerves in Whipples disease has not been documented convincingly so far. We present a case of Whipples disease presenting by axonal peripheral neuropathy without gastrointestinal involvement. The diagnosis was confirmed by a sural nerve biopsy and consequent PCR of the sample. All clinical signs disappeared progressively during the antibiotic therapy. Two years after the T. whipplei infection, the patient developed dopa-sensitive Parkinson's disease, although these two events seem to be unrelated. This case illustrates the value of peripheral nerve biopsy in cases of axonal neuropathy of unexplained origin and extends the clinical spectrum of Whipples disease to a new modality. Persson, Anna-Karin; Hoeijmakers, Janneke G J; Estacion, Mark; Black, Joel A; Waxman, Stephen G Peripheral neuropathy results from damage to peripheral nerves and is often accompanied by pain in affected limbs. Treatment represents an unmet medical need and a thorough understanding of the mechanisms underlying axonal injury is needed. Longer nerve fibers tend to degenerate first (length-dependence), and patients carrying pathogenic mutations throughout life usually become symptomatic in mid- or late-life (time-dependence). The activity of voltage-gated sodium channels can contribute to axonal injury and sodium channel gain-of-function mutations have been linked to peripheral neuropathy. Recent studies have implicated sodium channel activity, mitochondrial compromise, and reverse-mode Na(+)/Ca(2+) exchange in time- and length-dependent axonal injury. Elucidation of molecular mechanisms underlying axonal injury in peripheral neuropathy may provide new therapeutic strategies for this painful and debilitating condition. Vasculitic peripheral neuropathy (VPN) occurs due to ischemic changes of peripheral nerves, resulting from a deficit of vascular blood supply due to damaged vasa nervorum leading to vasculitis. VPN usually manifests as sensorimotor or sensory disturbances accompanied by pain, presenting as a type of multiple mononeuropathy, with a scattered distribution in distal limbs. VPN may also present as a mononeuropathy, distal symmetric polyneuropathy, plexopathy, or radiculopathy. The rapidity of VPN is variable, ranging from days to months, with symptoms occasionally changing with the appearance of new lesions. Careful history taking and neurological examination provides an exact diagnosis. The most common cause of VPN is primary vasculitis predominantly affecting small vessels, including vasa nervorum, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and polyarteritis nodosa. Similar vasculitic processes can also result from a systemic collagen disorder or secondary vasculitis. Electrophysiological studies and pathological investigation of biopsied peripheral nerves and muscles are important for diagnosis of vasculitis. Serological tests, including ANCA, are useful for diagnosis of vasculitis. Accurate neurological examinations are essential for diagnosis and evaluation of clinical course. Han, Yaqin; Smith, Maree T. Chemotherapy induced peripheral neuropathy (CIPN) is a type of neuropathic pain that is a major dose-limiting side-effect of potentially curative cancer chemotherapy treatment regimens that develops in a “stocking and glove” distribution. When pain is severe, a change to less effective chemotherapy agents may be required, or patients may choose to discontinue treatment. Medications used to alleviate CIPN often lack efficacy and/or have unacceptable side-effects. Hence the unmet medical need for novel analgesics for relief of this painful condition has driven establishment of rodent models of CIPN. New insights on the pathobiology of CIPN gained using these models are discussed in this review. These include mitochondrial dysfunction and oxidative stress that are implicated as key mechanisms in the development of CIPN. Associated structural changes in peripheral nerves include neuronopathy, axonopathy and/or myelinopathy, especially intra-epidermal nerve fiber (IENF) degeneration. In patients with CIPN, loss of heat sensitivity is a hallmark symptom due to preferential damage to myelinated primary afferent sensory nerve fibers in the presence or absence of demyelination. The pathobiology of CIPN is complex as cancer chemotherapy treatment regimens frequently involve drug combinations. Adding to this complexity, there are also subtle differences in the pathobiological consequences of commonly used cancer chemotherapy drugs, viz platinum compounds, taxanes, vincristine, bortezomib, thalidomide and ixabepilone, on peripheral nerves. PMID:24385965 Kelly, John J In this, the third of a 3-part series on peripheral neuropathy, the syndromes of vasculitic, infectious, inherited, and idiopathic neuropathy are discussed. Vasculitis is a frequent cause of neuropathy in the setting of a connective tissue disease. The infectious neuropathies most likely to be encountered in the United States are those due to varicella-zoster virus, human immunodeficiency virus, Lyme disease, hepatitis C virus, and, most recently, West Nile virus. Inherited neuropathies are divided into 2 main types: predominant motor or predominant sensory. The former are generally classed as the Charcot-Marie-Tooth diseases and the latter as the hereditary sensory neuropathies. Each category has a number of different subtypes. If the results of routine screening tests are negative, the clinician must consider special testing for unusual disorders, including evaluations for underlying autoimmune or malignant disorders, genetic tests for inherited neuropathies, and other unusual or selectively ordered tests. These tests are very expensive and should be ordered only after the common causes of neuropathy are excluded. Unless the neuropathy can be substantially alleviated or cured, symptomatic treatment (most often for pain) plays a significant role for these patients. Menezes, Manoj P; Rahman, Shamima; Bhattacharya, Kaustuv; Clark, Damian; Christodoulou, John; Ellaway, Carolyn; Farrar, Michelle; Pitt, Matthew; Sampaio, Hugo; Ware, Tyson L; Wedatilake, Yehani; Thorburn, David R; Ryan, Monique M; Ouvrier, Robert Peripheral nerve involvement is common in mitochondrial disease but often unrecognised due to the prominent central nervous system features. Identification of the underlying neuropathy may assist syndrome classification, targeted genetic testing and rehabilitative interventions. Clinical data and the results of nerve conduction studies were obtained retrospectively from the records of four tertiary children's hospital metabolic disease, neuromuscular or neurophysiology services. Nerve conductions studies were also performed prospectively on children attending a tertiary metabolic disease service. Results were classified and analysed according to the underlying genetic cause. Nerve conduction studies from 27 children with mitochondrial disease were included in the study (mitochondrial DNA (mtDNA) - 7, POLG - 7, SURF1 - 10, PDHc deficiency - 3). Four children with mtDNA mutations had a normal study while three had mild abnormalities in the form of an axonal sensorimotor neuropathy when not acutely unwell. One child with MELAS had a severe acute axonal motor neuropathy during an acute stroke-like episode that resolved over 12months. Five children with POLG mutations and disease onset beyond infancy had a sensory ataxic neuropathy with an onset in the second decade of life, while the two infants with POLG mutations had a demyelinating neuropathy. Seven of the 10 children with SURF1 mutations had a demyelinating neuropathy. All three children with PDHc deficiency had an axonal sensorimotor neuropathy. Unlike CMT, the neuropathy associated with mitochondrial disease was not length-dependent. This is the largest study to date of peripheral neuropathy in genetically- classified childhood mitochondrial disease. Characterising the underlying neuropathy may assist with the diagnosis of the mitochondrial syndrome and should be an integral part of the assessment of children with suspected mitochondrial disease. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society Tenenbein, M; deGroot, W; Rajani, K R Two adolescent native Canadians who presented with peripheral neuropathy secondary to the abuse of volatile hydrocarbons are described. They were initially thought to have been sniffing leaded gasoline fumes, but public health investigation revealed that they had been sniffing naphtha fumes. Naphtha contains a significant amount of n-hexane, a known inducer of neuropathy. Nerve conduction studies and nerve biopsy confirmed the diagnosis of naphtha abuse. These cases emphasize the need to specifically identify the formulation of hydrocarbons being abused. Tenenbein, M; deGroot, W; Rajani, K R Two adolescent native Canadians who presented with peripheral neuropathy secondary to the abuse of volatile hydrocarbons are described. They were initially thought to have been sniffing leaded gasoline fumes, but public health investigation revealed that they had been sniffing naphtha fumes. Naphtha contains a significant amount of n-hexane, a known inducer of neuropathy. Nerve conduction studies and nerve biopsy confirmed the diagnosis of naphtha abuse. These cases emphasize the need to specifically identify the formulation of hydrocarbons being abused. PMID:6093978 Hussain, Gauhar; Rizvi, S Aijaz Abbas; Singhal, Sangeeta; Zubair, Mohammad; Ahmad, Jamal To compare serum levels of TNF-α in patients of peripheral neuropathy and patients without neuropathy in type 2 diabetes mellitus. This cross sectional study was conducted in diagnosed type 2 diabetes mellitus patients. They were divided in groups, Group I (n=37) with clinically detectable diabetic peripheral neuropathy of shorter duration and Group II (n=27) with clinically detectable diabetic peripheral neuropathy of longer duration. They were compared with patients without clinical neuropathy (n=22), clinical diagnosis was based on neuropathy symptom score (NSS) and neuropathy disability score (NDS) for signs. Blood samples were collected for baseline investigations and estimation of serum TNF-α. Nerve conduction velocity was measured in both upper and lower limbs. Median, Ulnar, Common Peroneal and Posterior Tibial nerves were selected for motor nerve conduction study and Median and Sural nerves were selected for sensory nerve conduction study. The comparisons were done between various clinical and biochemical parameters in clinically detectable and undetectable peripheral neuropathy groups of type 2 diabetes mellitus. The study showed raised serum levels of TNF-α in peripheral neuropathy patients and significant correlation with nerve conduction velocity. High level of TNF-α in serum of T2DM patients with neuropathy shows possible contribution in development of neuropathy. Due to its independent association this cytokine might be used as biomarker for diabetic peripheral neuropathy. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved. Ben-Horin, Idan; Kahan, Peretz; Ryvo, Larisa; Inbar, Moshe; Lev-Ari, Shahar; Geva, Ravit Treatment of chemotherapy-induced peripheral neuropathy (CIPN), which affects approximately 30% to 40% of patients treated with neuropathy-causing agents, is mainly symptomatic. Currently available interventions are of little benefit. This study was conducted as a retrospective analysis of the efficacy of acupuncture and reflexology in alleviating CIPN in breast cancer patients. Medical records of 30 consecutive breast cancer patients who received both chemotherapy and treatment for CIPN according to our Acupuncture and Reflexology Treatment for Neuropathy (ART-N) protocol between 2011 and 2012 were reviewed. Symptom severity was rated at baseline, during, and after treatment. The records of 30 breast cancer patients who had been concomitantly treated with chemotherapy and ART-N for CIPN were retrieved. Two records were incomplete, leaving a total of 28 patients who were enrolled into the study. Twenty patients (71%) had sensory neuropathy, 7 (25%) had motor neuropathy, and 1 (4%) had both sensory and motor neuropathy. Only 2 (10%) of the 20 patients with grades 1 to 2 neuropathy still reported symptoms at 12 months since starting the ART-N protocol. All 8 patients who presented with grades 3 to 4 neuropathy were symptom-free at the 12-month evaluation. Overall, 26 patients (93%) had complete resolution of CIPN symptoms. The results of this study demonstrated that a joint protocol of acupuncture and reflexology has a potential to improve symptoms of CIPN in breast cancer patients. The protocol should be validated on a larger cohort with a control group. It also warrants testing as a preventive intervention. Ylitalo, Kelly R.; Herman, William H.; Harlow, Siobán D. Peripheral neuropathy is underappreciated as a potential cause of functional limitations. In the present article, we assessed the cross-sectional association between peripheral neuropathy and physical functioning and how the longitudinal association between age and functioning differed by neuropathy status. Physical functioning was measured in 1996–2008 using timed performances on stair-climb, walking, sit-to-stand, and balance tests at the Michigan site of the Study of Women's Health Across the Nation, a population-based cohort study of women at midlife (n = 396). Peripheral neuropathy was measured in 2008 and defined as having an abnormal monofilament test result or 4 or more symptoms. We used linear mixed models to determine whether trajectories of physical functioning differed by prevalent neuropathy status. Overall, 27.8% of the women had neuropathy. Stair-climb time differed by neuropathy status (P = 0.04), and for every 1-year increase in age, women with neuropathy had a 1.82% (95% confidence interval: 1.42, 2.21) increase compared with a 0.95% (95% confidence interval: 0.71, 1.20) increase for women without neuropathy. Sit-to-stand time differed by neuropathy status (P = 0.01), but the rate of change did not differ. No differences between neuropathy groups were observed for the walk test. For some performance-based tasks, poor functioning was maintained or exacerbated for women who had prevalent neuropathy. Peripheral neuropathy may play a role in physical functioning limitations and future disability. PMID:23524038 Srinivasan, Sangeetha; Pritchard, Nicola; Sampson, Geoff P; Edwards, Katie; Vagenas, Dimitrios; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan To examine the diagnostic capability of the full retinal and inner retinal thickness measures in differentiating individuals with diabetic peripheral neuropathy (DPN) from those without neuropathy and non-diabetic controls. Individuals with (n=44) and without (n=107) diabetic neuropathy and non-diabetic control (n=42) participants underwent spectral domain optical coherence tomography (SDOCT). Retinal thickness in the central 1mm zone (including the fovea), parafovea and perifovea was assessed in addition to ganglion cell complex (GCC) global loss volume (GCC GLV) and focal loss volume (GCC FLV), and retinal nerve fiber layer (RNFL) thickness. Diabetic neuropathy was defined using a modified neuropathy disability score (NDS) recorded on a 0-10 scale, wherein, NDS ≥3 indicated neuropathy and NDS indicated <3 no neuropathy. Diagnostic performance was assessed by areas under the receiver operating characteristic curves (AUCs), 95 per cent confidence intervals (CI), sensitivities at fixed specificities, positive likelihood ratio (+LR), negative likelihood ratio (-LR) and the cut-off points for the best AUCs obtained. The AUC for GCC FLV was 0.732 (95% CI: 0.624-0.840, p<0.001) with a sensitivity of 53% and specificity of 80% for differentiating DPN from controls. Evaluation of the LRs showed that GCC FLV was associated with only small effects on the post-test probability of the disease. The cut-off point calculated using the Youden index was 0.48% (67% sensitivity and 73% specificity) for GCC FLV. For distinguishing those with neuropathy from those without neuropathy, the AUCs of retinal parameters ranged from 0.508 for the central zone to 0.690 for the inferior RNFL thickness. For distinguishing those with moderate or advanced neuropathy from those with mild or no neuropathy, the inferior RNFL thickness demonstrated the highest AUC of 0.820, (95% CI: 0.731-0.909, p<0.001) with a sensitivity of 69% and 80% specificity. The cut-off-point for the inferior RNFL Grimm, Alexander; Décard, Bernhard F; Bischof, Antje; Axer, Hubertus Ultrasound of the peripheral nerves (PNUS) can be used to visualize nerve pathologies in polyneuropathies (PNP). The aim of this study was to investigate, whether PNUS provides additional information in patients with proven systemic vasculitic neuropathies (VN). Systematic ultrasound measurements of several peripheral nerves, the vagal nerve and the 6th cervical nerve root were performed in 14 patients and 22 healthy controls. Nerve conduction studies of the corresponding nerves were undertaken. Finally, the measured results were compared to a study population of demyelinating immune-mediated and axonal neuropathies. Patients with VN displayed significant smaller amplitudes of compound muscle action potentials (CMAP) (p<0.05) and sensory nerve action potentials (SNAP) compared to healthy controls, while conduction velocity did not differ between groups. The mean nerve cross-sectional areas (CSA) were increased in several peripheral nerves compared to the controls, most prominent in tibial and fibular nerve (p<0.01). PNUS revealed nerve enlargement in most of the clinically and electrophysiologically affected nerves (22 out of 31) in VN. Nerve enlargement was more often seen in vasculitic neuropathies than in other axonal neuropathies, but significantly rarer than in demyelinating neuropathies. Focal CSA enlargement in one or more nerves in electrophysiologically axonal neuropathies can be a hint for VN and thus facilitate diagnostic and therapeutic procedures. Copyright © 2014 Elsevier B.V. All rights reserved. Brewer, Jamie R; Morrison, Gladys; Dolan, M Eileen; Fleming, Gini F As there are increasing numbers of cancer survivors, more attention is being paid to the long term unwanted effects patients may experience as a result of their treatment and the impact these side effects can have on their quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxicities from chemotherapy. In this review we will briefly review the clinical presentation, evaluation and management of chemotherapy-induced peripheral neuropathy, with a focus on CIPN related to platinum and taxane agents. We will then discuss current clinical models of peripheral neuropathy and ongoing research to better understand CIPN and develop potential treatment options. Copyright © 2015 Elsevier Inc. All rights reserved. Sathya, G R; Krishnamurthy, N; Veliath, Susheela; Arulneyam, Jayanthi; Venkatachalam, J Each skeletal muscle is usually supplied by two or more nerve roots and if one nerve root is affected and the other is spared, the clinically used F wave minimum latency can still be normal. An F wave index was constructed taking into consideration the other parameters of the F wave such as persistence, chronodispersion, latency, arm-length to determine its usefulness in the diagnosis of peripheral neuropathy. This study was undertaken to construct the F wave index in the upper limb for the median nerve in normal healthy adult males and in patients with peripheral neuropathy and to compare the values obtained in both groups. This hospital-based study was carried out on 40 males who were diagnosed to have peripheral neuropathy and on 40 age matched healthy males who served as the control group. The F wave recording was done using a digitalized nerve conduction/electromyography/EP machine in a quiet and dimly lit room. All recordings were done between 0900 and 1100 h at an ambient temperature of 22°C. The F wave recording was obtained from a fully relaxed muscle by stimulating the median nerve. The median value for F wave index obtained from median nerve (abductor pollicis brevis) in patients with peripheral neuropathy [right arm - 35.85, interquartile range (IQR) - 35.26; left arm - 39.49, IQR - 39.49] was significantly lower (P=0.001) as compared to the control group (right arm - 102.62, IQR - 83.76; left arm - 77.43, IQR - 58.02). Our results showed that F wave index in upper limb was significantly lower in patients with peripheral neuropathy than the healthy controls, and could be used for early detection of peripheral neuropathy. Sathya, G. R.; Krishnamurthy, N.; Veliath, Susheela; Arulneyam, Jayanthi; Venkatachalam, J. Background & objectives: Each skeletal muscle is usually supplied by two or more nerve roots and if one nerve root is affected and the other is spared, the clinically used F wave minimum latency can still be normal. An F wave index was constructed taking into consideration the other parameters of the F wave such as persistence, chronodispersion, latency, arm-length to determine its usefulness in the diagnosis of peripheral neuropathy. This study was undertaken to construct the F wave index in the upper limb for the median nerve in normal healthy adult males and in patients with peripheral neuropathy and to compare the values obtained in both groups. Methods: This hospital-based study was carried out on 40 males who were diagnosed to have peripheral neuropathy and on 40 age matched healthy males who served as the control group. The F wave recording was done using a digitalized nerve conduction/electromyography/EP machine in a quiet and dimly lit room. All recordings were done between 0900 and 1100 h at an ambient temperature of 22°C. The F wave recording was obtained from a fully relaxed muscle by stimulating the median nerve. Results: The median value for F wave index obtained from median nerve (abductor pollicis brevis) in patients with peripheral neuropathy [right arm - 35.85, interquartile range (IQR) - 35.26; left arm - 39.49, IQR - 39.49] was significantly lower (P=0.001) as compared to the control group (right arm - 102.62, IQR - 83.76; left arm - 77.43, IQR - 58.02). Interpretation & conclusions: Our results showed that F wave index in upper limb was significantly lower in patients with peripheral neuropathy than the healthy controls, and could be used for early detection of peripheral neuropathy. PMID:28749398 Gentile, S; Marmo, R; Costume, A; Persico, M; Bronzino, P; Contaldi, P; Stroffolini, T The clinical conditions due to damage to the peripheral sympathetic nervous system during diabetic neuropathy mainly involve alterations to subcutaneous vasomotility , temperature body regulation and exudation, which may take form of hyper or hypoactivity. Gustatory exudation and local anhydrosis are described in detail as well as the connection with aggravating factors like long duration, poor balance and early onset of diabetes mellitus . Change in the relevant cardiovascular reflexes, commonly used in diagnosing diabetic neuropathy, are also analysed with a discussion of their physiopathological background and clinical significance. Finally the painless infarct, sudden death and abnormal response to hypoglycaemia, that are the common features of diabetic neuropathy, are also described. Tofthagen, Cindy; Kip, Kevin E; Passmore, Denise; Loy, Ian; Berry, Donna L Chemotherapy-induced neuropathy is a painful and debilitating adverse effect of certain chemotherapy drugs. There have not been any patient-centered, easily accessible Web-based interventions to assist with self-management of chemotherapy-induced neuropathy. The aims of this study were to evaluate usability and acceptability and to estimate an effect size of a Web-based intervention for assessing and managing chemotherapy-induced neuropathy. Participants (N = 14) were instructed to complete the Creativity, Optimism, Planning, and Expert Information for Chemotherapy-Induced Peripheral Neuropathy program and provide verbal responses to the program. Participants completed the Chemotherapy Induced Peripheral Neuropathy Assessment Tool and Post-Study System Usability Questionnaire. Iterative changes were made to the COPE-CIPN. Participants were asked to provide feedback on the revised COPE-CIPN, repeat the Chemotherapy Induced Peripheral Neuropathy Assessment Tool, and evaluate acceptability using the Acceptability e-Scale. The COPE-CIPN demonstrated high usability (mean, 1.98 [SD, 1.12]) and acceptability (mean, 4.40 [SD, 0.52]). Comments indicated that the interface was easy to use, and the information was helpful. While neuropathy symptoms continued to increase in this group of patients receiving neurotoxic chemotherapy, there was a decrease in mean level of interference with activities from 53.71 to 39.29 over 3 to 4 months, which indicated a moderate effect (d = 0.39) size. The COPE-CIPN may be a useful intervention to support self-management of chemotherapy-induced neuropathy. Schuler, U; Heller, S The perception of the media is that chemotherapy is mainly associated with nausea, vomiting and hair loss. In the longer term the development of peripheral neuropathy, i.e. chemotherapy-induced peripheral neuropathy (CIPN) is often more important for patients. The CIPN represents a side effect of many antineoplastic substances with severe functional impairment and its prevention and treatment is an important task. In addition to many interventions, which have been shown to be ineffective, physiotherapeutic measures and possibly the prophylactic application of cold are helpful for prevention. Randomized studies on the treatment of painful CIPN provided positive data for duloxetine and to a lesser extent for venlafaxine. Farmer, Kevin L.; Li, Chengyuan Diabetic peripheral neuropathy (DPN) is a common complication of diabetes that is associated with axonal atrophy, demyelination, blunted regenerative potential, and loss of peripheral nerve fibers. The development and progression of DPN is due in large part to hyperglycemia but is also affected by insulin deficiency and dyslipidemia. Although numerous biochemical mechanisms contribute to DPN, increased oxidative/nitrosative stress and mitochondrial dysfunction seem intimately associated with nerve dysfunction and diminished regenerative capacity. Despite advances in understanding the etiology of DPN, few approved therapies exist for the pharmacological management of painful or insensate DPN. Therefore, identifying novel therapeutic strategies remains paramount. Because DPN does not develop with either temporal or biochemical uniformity, its therapeutic management may benefit from a multifaceted approach that inhibits pathogenic mechanisms, manages inflammation, and increases cytoprotective responses. Finally, exercise has long been recognized as a part of the therapeutic management of diabetes, and exercise can delay and/or prevent the development of painful DPN. This review presents an overview of existing therapies that target both causal and symptomatic features of DPN and discusses the role of up-regulating cytoprotective pathways via modulating molecular chaperones. Overall, it may be unrealistic to expect that a single pharmacologic entity will suffice to ameliorate the multiple symptoms of human DPN. Thus, combinatorial therapies that target causal mechanisms and enhance endogenous reparative capacity may enhance nerve function and improve regeneration in DPN if they converge to decrease oxidative stress, improve mitochondrial bioenergetics, and increase response to trophic factors. PMID:22885705 Wei, Yi-Chia; Huang, Chin-Chang; Liu, Chi-Hung; Kuo, Hung-Chou; Lin, Jainn-Jim Autoantibodies to the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and N-methyl-d-aspartate (NMDA) receptor are known to be the causes of autoimmune encephalitis particularly limbic encephalitis. The involvement of the peripheral nervous system is rarely reported. We analyzed the serial nerve conduction studies of a previously reported case of anti-AMPA receptor encephalitis, who was presented with conscious disturbance and quadriplegia. Initial nerve conduction studies (NCS) revealed motor axonal polyneuropathy with active denervation. We also performed systematic review of similar cases with overlapped peripheral neuropathy and glutamate receptor encephalitis through Embase, PubMed, and MEDLINE. Follow-up NCS of the patient with anti-AMPA receptor encephalitis found reverse of the acute neuropathy, which was compatible with clinical recovery of quadriplegia. The systematic review identified 10 cases with overlapping peripheral neuropathy with anti-AMPA or NMDA receptor encephalitis. Motor or sensorimotor neuropathies were more common than pure sensory neuropathies. Anti-Hu, anti-amphiphysin, or anti-gnaglioside antibodies coexisted in some cases and might be associated with the peripheral symptoms. Both anti-AMPA and anti-NMDA receptor encephalitis could overlap with acute peripheral neuropathy. It is important to consider peripheral symptoms and perform diagnostic tests. Ushio, Soichiro; Egashira, Nobuaki; Sada, Hikaru; Kawashiri, Takehiro; Shirahama, Masafumi; Masuguchi, Ken; Oishi, Ryozo Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Goshajinkigan (GJG) is a Kampo medicine that is used for the treatments of several neurological symptoms including pain and numbness. More recently, GJG has been reported to prevent the oxaliplatin-induced peripheral neuropathy in clinical studies. No experimental study, however, has been conducted to date to determine the effect of GJG on pain behaviour in a rat model of oxaliplatin-induced neuropathy. Moreover, the impact on the anti-tumour effect of oxaliplatin remains unknown. In the present study, we examined the effects of GJG on the peripheral neuropathy and anti-tumour activity of oxaliplatin in rodents. Repeated administration of oxaliplatin caused cold hyperalgesia from days 3 to 37 and mechanical allodynia from days 21 to 28. Repeated administration of GJG prevented the oxaliplatin-induced cold hyperalgesia but not mechanical allodynia and axonal degeneration in rat sciatic nerve. Single administration of GJG reduced both cold hyperalgesia and mechanical allodynia after the development of neuropathy. In addition, GJG did not affect the anti-tumour effect of oxaliplatin in the tumour cells or tumour cells-implanted mice. These results suggest that GJG relieves the oxaliplatin-induced cold hyperalgesia and mechanical allodynia without affecting anti-tumour activity of oxaliplatin, and, therefore, may be useful for the oxaliplatin-induced neuropathy in clinical practice. Hernández-Zamora, Edgar; Arenas-Sordo, María de la Luz Peripheral neuropathies include a wide range of pathological disorders characterized by damage of peripheral nerves. Among them, peripheral hereditary neuropathies are a group of frequent illnesses and early evolution. They have been named hereditary motor and sensory neuropathy (HMSN) or peripheral hereditary neuropathies type Charcot-Marie-Tooth (CMT). The most frequent types are CMT1, CMT2 and CMTX. Approximately 70% of the cases correspond to subtype CMT1A, associated with tandem duplication of a 1.5 Mb DNA fragment on chromosome 17p11.2-p12 that codifies the peripheral myelin protein PMP22. So far, there five different types of CMT (1,2,3,4,X) with approximately 32 subtypes, associated with more than 30 genes. Have been reported genetic heterogeneity and expression variability of the illness makes it necessary to carry on diagnostic strategies that integrate clinical study for determining genetic clinical history, family history, complete physical exploration, muscular strength, physical deformities, reflexes and sensitivity, and molecular studies allow detection of different types of mutations and help establish a correct diagnosis and an adequate genetic counseling. Kunhimangalam, Reeda; Ovallath, Sujith; Joseph, Paul K The prevalence of peripheral neuropathy in general population is ever increasing. The diagnosis and classification of peripheral neuropathies is often difficult as it involves careful clinical and electro-diagnostic examination by an expert neurologist. In developing countries a large percentage of the disease remains undiagnosed due to lack of adequate number of experts. In this study a novel clinical decision support system has been developed using a fuzzy expert system. The study was done to provide a solution to the demand of systems that can improve health care by accurate diagnosis in limited time, in the absence of specialists. It employs a graphical user interface and a fuzzy logic controller with rule viewer for identification of the type of peripheral neuropathy. An integrated medical records database is also developed for the storage and retrieval of the data. The system consists of 24 input fields, which includes the clinical values of the diagnostic test and the clinical symptoms. The output field is the disease diagnosis, whether it is Motor (Demyelinating/Axonopathy) neuropathy, sensory (Demyelinating/Axonopathy) neuropathy, mixed type or a normal case. The results obtained were compared with the expert's opinion and the system showed 93.27 % accuracy. The study aims at showing that Fuzzy Expert Systems may prove useful in providing diagnostic and predictive medical opinions. It enables the clinicians to arrive at a better diagnosis as it keeps the expert knowledge in an intelligent system to be used efficiently and effectively. Rossor, Alexander M; Carr, Aisling S; Devine, Helen; Chandrashekar, Hoskote; Pelayo-Negro, Ana Lara; Pareyson, Davide; Shy, Michael E; Scherer, Steven S; Reilly, Mary M Peripheral neuropathy is a common finding in patients with complex inherited neurological diseases and may be subclinical or a major component of the phenotype. This review aims to provide a clinical approach to the diagnosis of this complex group of patients by addressing key questions including the predominant neurological syndrome associated with the neuropathy, for example, spasticity, the type of neuropathy and the other neurological and non-neurological features of the syndrome. Priority is given to the diagnosis of treatable conditions. Using this approach, we associated neuropathy with one of three major syndromic categories: (1) ataxia, (2) spasticity and (3) global neurodevelopmental impairment. Syndromes that do not fall easily into one of these three categories can be grouped according to the predominant system involved in addition to the neuropathy, for example, cardiomyopathy and neuropathy. We also include a separate category of complex inherited relapsing neuropathy syndromes, some of which may mimic Guillain-Barré syndrome, as many will have a metabolic aetiology and be potentially treatable. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Ennis, Samantha L; Galea, Mary P; O'Neal, David N; Dodson, Michael J Peripheral sensorimotor neuropathy is a recognised complication of diabetes mellitus however little attention has been given to its development in the hands. The aim of this study was to determine the prevalence of sensory impairment in the hands of participants with diabetes, the agreement between two measurement tools for assessing sensation and the association between hand sensibility, age, glycaemic control and end-organ damage. A total of 162 participants were recruited and divided into two cohorts based on a diagnosis of diabetes. Participants were tested for the presence of hand neuropathy using Semmes-Weinstein monofilaments and the AsTex™. Medical records of participants with diabetes were accessed retrospectively to determine glycaemic control and diabetes complications. A highly statistically significant association was found between neuropathy and diabetes status (P<0.001) on monofilament testing. The prevalence of neuropathy was 64% compared to ∼10% amongst participants without diabetes. Age, male gender and diabetic retinopathy were associated with neuropathy. The AsTex™ identified participants with diminished protective sensation on monofilament testing. This study demonstrates a relationship between diabetes and upper limb neuropathy. Age, male gender and retinopathy were associated with diminished hand sensation. The AsTex™ may have a role as a screening tool for identifying clinically significant hand neuropathy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. Donadio, Vincenzo; Incensi, Alex; Giannoccaro, Maria Pia; Cortelli, Pietro; Di Stasi, Vitantonio; Pizza, Fabio; Jaber, Masen Abdel; Baruzzi, Agostino; Liguori, Rocco Skin biopsy has gained widespread use for the diagnosis of somatic small-fiber neuropathy, but it also provides information on sympathetic fiber morphology. We aimed to ascertain the diagnostic accuracy of skin biopsy in disclosing sympathetic nerve abnormalities in patients with autonomic neuropathy. Peripheral nerve fiber autonomic involvement was confirmed by routine autonomic laboratory test abnormalities. Punch skin biopsies were taken from the thigh and lower leg of 28 patients with various types of autonomic neuropathy for quantitative evaluation of skin autonomic innervation. Results were compared with scores obtained from 32 age-matched healthy controls and 25 patients with somatic neuropathy. The autonomic cutoff score was calculated using the receiver operating characteristic curve analysis. Skin biopsy disclosed a significant autonomic innervation decrease in autonomic neuropathy patients versus controls and somatic neuropathy patients. Autonomic innervation density was abnormal in 96% of patients in the lower leg and in 79% of patients in the thigh. The abnormal findings disclosed by routine autonomic tests ranged from 48% to 82%. These data indicate the high sensitivity and specificity of skin biopsy in detecting sympathetic abnormalities; this method should be useful for the diagnosis of autonomic neuropathy, together with currently available routine autonomic testing. Myotonic dystrophy type 2 (dystrophia myotonica type 2-DM2) is an autosomal dominant multi-organ disorder. The involvement of the peripheral nervous system was found in 25%-45% of patients with myotonic dystrophy type 1, although limited data are available concerning polyneuropathy in patients with DM2, which was the aim of this study with a thorough presentation of the cases with peripheral neuropathy. Patients with genetically confirmed DM2 underwent motor nerve conduction studies of the median, ulnar, tibial and fibular nerves and sensory nerve conduction studies of the median (second finger), ulnar (fifth finger), radial (forearm) and sural nerves. Seventeen adult patients with DM2 participated in the study. Fifty-three percent (9/17) of our patients had abnormality of one or more attributes (latency, amplitude or conduction velocity) in two or more separate nerves. Four types of neuropathies were found: (i) predominantly axonal motor and sensory polyneuropathy, (ii) motor polyneuropathy, (iii) predominantly demyelinating motor and sensory polyneuropathy and (iv) mutilating polyneuropathy with ulcers. The most common forms are axonal motor and sensory polyneuropathy (29%) and motor neuropathy (18% of all examined patients). No correlations were found between the presence of neuropathy and age, CCTG repeats, blood glucose or HbA1C. Peripheral neuropathy is common in patients with DM2 and presents one of the multisystemic manifestations of DM2. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Kambiz, Shoista; van Neck, Johan W.; Cosgun, Saniye G.; van Velzen, Marit H. N.; Janssen, Joop A. M. J. L.; Avazverdi, Naim; Hovius, Steven E. R.; Walbeehm, Erik T. The skin’s rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study was to investigate whether the skin rewarming rate in diabetic rats is related to microvascular changes and whether this is accompanied by changes observed in classical diagnostic methods for diabetic peripheral neuropathy. Computer-assisted infrared thermography was used to assess the rewarming rate after cold exposure on the plantar skin of STZ diabetic rats’ hind paws. Peripheral neuropathy was determined by the density of intra-epidermal nerve fibers (IENFs), mechanical sensitivity, and electrophysiological recordings. Data were obtained in diabetic rats at four, six, and eight weeks after the induction of diabetes and in controls. Four weeks after the induction of diabetes, a delayed rewarming rate, decreased skin blood flow and decreased density of IENFs were observed. However, the mechanical hyposensitivity and decreased motor nerve conduction velocity (MNCV) developed 6 and 8 weeks after the induction of diabetes. Our study shows that the skin rewarming rate is related to microvascular changes in diabetic rats. Moreover, the skin rewarming rate is a non-invasive method that provides more information for an earlier diagnosis of peripheral neuropathy than the classical monofilament test and MNCV in STZ induced diabetic rats. PMID:25984949 Mo, Michelle; Erdelyi, Ildiko; Szigeti-Buck, Klara; Benbow, Jennifer H.; Ehrlich, Barbara E. Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect that occurs in many patients undergoing chemotherapy. It is often irreversible and frequently leads to early termination of treatment. In this study, we have identified two compounds, lithium and ibudilast, that when administered as a single prophylactic injection prior to paclitaxel treatment, prevent the development of CIPN in mice at the sensory-motor and cellular level. The prevention of neuropathy was not observed in paclitaxel-treated mice that were only prophylactically treated with a vehicle injection. The coadministration of lithium with paclitaxel also allows for administration of higher doses of paclitaxel (survival increases by 60%), protects against paclitaxel-induced cardiac abnormalities, and, notably, does not interfere with the antitumor effects of paclitaxel. Moreover, we have determined a mechanism by which CIPN develops and have discovered that lithium and ibudilast inhibit development of peripheral neuropathy by disrupting the interaction between paclitaxel, neuronal calcium sensor 1 (NCS-1), and the inositol 1,4,5-trisphosphate receptor (InsP3R) to prevent treatment-induced decreases in intracellular calcium signaling. This study shows that lithium and ibudilast are candidate therapeutics for the prevention of paclitaxel-induced neuropathy and could enable patients to tolerate more aggressive treatment regimens.—Mo, M., Erdelyi, I., Szigeti-Buck, K., Benbow, J. H., Ehrlich, B. E. Prevention of paclitaxel-induced peripheral neuropathy by lithium pretreatment. PMID:22889832 Holisaz, Mohammad Taghi; Rayegani, Seyyed Mansoor; Hafezy, Rahmatollah; Khedmat, Hossein; Motamedi, Mohammad Hosein K We aimed to assess the prevalence of peripheral neuropathy in chemical warfare victims. We speculated that peripheral neuropathy is a late complication of exposure to chemical warfare agents. Late complications of exposure to chemical warfare agents are not well known and are poorly discussed in the existing literature. Scientific data regarding delayed complications are sparse, but this warrants recognition, especially when the clinician has to treat chemical warfare victims. The hazards of organophosphate pesticides and several toxins, although recognized to some extent, are, however, different from the hazards of chemical warfare agents which are far more serious. In this study, 100 chemical warfare patients, with varying degrees of exposure and an average age of 37.2+/-9.0 years, were examined clinically and studied electrodiagnostically from January 2002 to January 2003. Five of these patients proved to be suffering from axonal neuropathy. This rate was significantly higher than that found in the normal population. Our data indicate that chemical warfare agents may cause peripheral neuropathy in chemical warfare victims. In conclusion, organophosphorous agents used against Iranian troops during the war on Iran correlate with delayed neuropathy in these victims. Scelsi, Roberto; Candura, Stefano M Many peripheral neuropathies are caused by the (acute or chronic) toxic action of metals, solvents, pesticides, and other occupational and environmental contaminants. These agents often reproduce the anatomoclinical pictures of hereditary (e.g., Charcot-Marie-Tooth disease), autoimmune (Guillain-Barrè syndrome), or dysmetabolic (thiamine deficiency, diabetic neuropathy) forms. Toxic peripheral neuropathies can be classified on the basis of etiology, clinical features (sensitive, motor, sensitive-motor), or histopathology: neuronopathies (uncommon, mostly secondary to retrograde axonal degeneration; e.g., arsenic, thallium), axonopathies (acrylamide, esacarbons, CS2, organophosphate-induced delayed neuropathy), myelinopathies (trichloroethylene), mixed forms (axonal and demyelinating: lead). For many substances, experimental research has led to the identification of the molecular and cellular targets of neurotoxicity. Several compounds are active by biotransformation (e.g., the esacarbons n-hexane and MnBK are neurotoxic since they are metabolized to 2,5-hexanedione), Genetic, physiological and environmental factors determine the individual metabolic set-up, and they may give origin to differences in the workers' sensitivity. Cessation of exposure is often followed by (microscopically observable) regenerative phenomena and clinical improvement. The morphology of neuropathies can be studied through peripheral nerve biopsy. Samples of sural nerve (or other nervous trunks of the limbs), adequately fixed, sectioned, and stained, allow the observation of alterations in axonal fibres (e.g., giant-axonal neuropathy, dying back neuropathy), myelin (demyelination), Schwann cells, interstitium, and blood vessels; possible inflammatory infiltrates; fibre density; regenerative phenomena (growth cone, remyelination). In occupational medicine, biopsy is indicated when the anamnestic-clinical picture, laboratory tests, and instrumental exams leave doubts about the nature, type Epplin-Zapf, Thomas; Miller, Clayton; Larkin, Sean; Hermesmeyer, Eduardo; Macy, Jenny; Pellegrini, Marco; Luccarelli, Saverio; Staurenghi, Giovanni; Holmes, Timothy A relationship has been reported by several research groups [1 - 4] between the density and shapes of nerve fibers in the cornea and the existence and severity of peripheral neuropathy. Peripheral neuropathy is a complication of several prevalent diseases or conditions, which include diabetes, HIV, prolonged alcohol overconsumption and aging. A common clinical technique for confirming the condition is intramuscular electromyography (EMG), which is invasive, so a noninvasive technique like the one proposed here carries important potential advantages for the physician and patient. A software program that automatically detects the nerve fibers, counts them and measures their shapes is being developed and tested. Tests were carried out with a database of subjects with levels of severity of diabetic neuropathy as determined by EMG testing. Results from this testing, that include a linear regression analysis are shown. Zhang, Yunqian; Li, Jintao; Wang, Tingjuan; Wang, Jianlin Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy. PMID:25221597 Zhang, Yunqian; Li, Jintao; Wang, Tingjuan; Wang, Jianlin Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy. Morgan, Megan J; Vite, Charles H; Radhakrishnan, Anant; Hess, Rebecka S Clinical and electrodiagnostic findings in 3 spontaneously diabetic dogs with clinical peripheral neuropathy (PN) are reported. Clinical signs of a PN may develop in diabetic dogs with adequate glycemic control. In addition, laryngeal paralysis may develop in association with diabetes mellitus in dogs with clinical PN. Jin, Jiewen; Wang, Weimin; Gu, Tianwei; Chen, Wei; Lu, Jing; Bi, Yan; Zhu, Dalong Purpose Diabetic peripheral neuropathies are the common chronic complications of diabetes, but the diagnosis is insensitive by physical examination in busy outpatients. Here we evaluated the performance of SUDOSCAN in screening diabetic peripheral neuropathies in Chinese type 2 diabetic patients. Methods The study enrolled 180 patients for annually screening. All patients underwent neurological symptoms assessment, clinical examination, nerve conduction studies and cardiovascular autonomic reflex tests. SUDOSCAN was tested and evaluated with electrochemical skin conductance in hands and feet, asymmetry ratio in hands and feet and predicted cardiac neuropathy. Results Patients enrolled had an average age of 56.1 years, 9.8 years of diabetic duration. Patients with diabetic sensorimotor polyneuropathy showed significantly lower electrochemical skin conductance in feet and higher asymmetry ratio in feet compared with those without. Sensitivity and specificity of asymmetry ratio in feet for diagnosing diabetic sensorimotor polyneuropathy were 88.2% and 46.9% and area under ROC curve was 0.713. Patients with cardiovascular autonomic neuropathy showed significantly lower electrochemical skin conductance in hands and feet, and higher asymmetry ratio in feet and predicted cardiac neuropathy compared with those without. Sensitivity and specificity of electrochemical skin conductance in feet in diagnosing cardiovascular autonomic neuropathy were 85.6% and 76.1% with an area under ROC curve of 0.859. Conclusions SUDOSCAN is a sensitive test to detect diabetic peripheral neuropathy in China and could be an effective screening tool in in busy outpatients and primary health care. © Georg Thieme Verlag KG Stuttgart · New York. Linnemann, Christoph; Tezenas du Montcel, Sophie; Rakowicz, Maryla; Schmitz-Hübsch, Tanja; Szymanski, Sandra; Berciano, Jose; van de Warrenburg, Bart P; Pedersen, Karine; Depondt, Chantal; Rola, Rafal; Klockgether, Thomas; García, Antonio; Mutlu, Gurkan; Schöls, Ludger Spinocerebellar ataxias (SCAs) are characterized by autosomal dominantly inherited progressive ataxia but are clinically heterogeneous due to variable involvement of non-cerebellar parts of the nervous system. Non-cerebellar symptoms contribute significantly to the burden of SCAs, may guide the clinician to the underlying genetic subtype, and might be useful markers to monitor disease. Peripheral neuropathy is frequently observed in SCA, but subtype-specific features and subclinical manifestations have rarely been evaluated. We performed a multicenter nerve conduction study with 162 patients with genetically confirmed SCA1, SCA2, SCA3, and SCA6. The study proved peripheral nerves to be involved in the neurodegenerative process in 82 % of SCA1, 63 % of SCA2, 55 % of SCA3, and 22 % of SCA6 patients. Most patients of all subtypes revealed affection of both sensory and motor fibers. Neuropathy was most frequently of mixed type with axonal and demyelinating characteristics in all SCA subtypes. However, nerve conduction velocities of SCA1 patients were slower compared to other genotypes. SCA6 patients revealed less axonal damage than patients with other subtypes. No influence of CAG repeat length or biometric determinants on peripheral neuropathy could be identified in SCA1, SCA3, and SCA6. In SCA2, earlier onset and more severe ataxia were associated with peripheral neuropathy. We proved peripheral neuropathy to be a frequent site of the neurodegenerative process in all common SCA subtypes. Since damage to peripheral nerves is readily assessable by electrophysiological means, nerve conduction studies should be performed in a longitudinal approach to assess these parameters as potential progression markers. Hansen, C S; Jensen, T M; Jensen, J S; Nawroth, P; Fleming, T; Witte, D R; Lauritzen, T; Sandbaek, A; Charles, M; Fleischer, J; Vistisen, D; Jørgensen, M E Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen-detected Type 2 diabetes (duration ~ 5.8 years). The patients were well controlled with regard to HbA(1c), lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy was assessed by vibration detection threshold (n = 319), 10 g monofilament (n = 543) and the Michigan Neuropathy Screening Instrument questionnaire (n = 966). Painful diabetic neuropathy was assessed using the Brief Pain Inventory short form (n = 882). No associations between methylglyoxal and cardiovascular autonomic reflex tests or any measures of diabetic peripheral neuropathy or painful diabetic neuropathy were observed. However, a positive association between methylglyoxal and several heart rate variability indices was observed, although these associations were not statistically significant when corrected for multiple testing. Serum methylglyoxal is not associated with cardiovascular autonomic neuropathy, diabetic peripheral neuropathy or painful diabetic neuropathy in this cohort of well-treated patients with short-term diabetes. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK. Antibodies directed to intracellular neural antigens have been mainly described in paraneoplastic peripheral neuropathies and mostly includes anti-Hu and anti-CV2/CRMP5 antibodies. These antibodies occur with different patterns of neuropathy. With anti-Hu antibody, the most frequent manifestation is sensory neuronopathy with frequent autonomic involvement. With anti-CV2/CRMP5 the neuropathy is more frequently sensory and motor with an axonal or mixed demyelinating and axonal electrophysiological pattern. The clinical pattern of these neuropathies is in keeping with the cellular distribution of HuD and CRMP5 in the peripheral nervous system. Although present in high titer, these antibodies are probably not directly responsible for the neuropathy. Pathological and experimental studies indicate that cytotoxic T-cells are probably the main effectors of the immune response. These disorders contrast with those in which antibodies recognize a cell surface antigen and are probably responsible for the disease. The neuronal cell death and axonal degeneration which result from T-cell mediated immunity explains why treating these disorders remains challenging. Copyright © 2014 Elsevier Masson SAS. All rights reserved. Srinivasan, Sangeetha; Pritchard, Nicola; Vagenas, Dimitrios; Edwards, Katie; Sampson, Geoff P; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan To investigate the relationship between diabetic peripheral neuropathy (DPN) and retinal tissue thickness. Full retinal thickness in the central retinal, parafoveal, and perifoveal zones and thickness of the ganglion cell complex and retinal nerve fiber layer (RNFL) were assessed in 193 individuals (84 with type 1 diabetes, 67 with type 2 diabetes, and 42 healthy controls) using spectral domain optical coherence tomography. Among those with diabetes, 44 had neuropathy defined using a modified neuropathy disability score recorded on a 0-10 scale. Multiple regression analysis was performed to investigate the relationship between diabetic neuropathy and retinal tissue thickness, adjusted for the presence of diabetic retinopathy (DR), age, sex, duration of diabetes, and HbA1c levels. In individuals with diabetes, perifoveal thickness was inversely related to the severity of neuropathy (p < 0.05), when adjusted for age, sex, duration of diabetes, and HbA1c levels. DR was associated with reduced thickness in parafovea (p < 0.01). The RNFL was thinner in individuals with greater degrees of neuropathy (p < 0.04). DPN is associated with structural compromise involving several retinal layers. This compromise may represent a threat to visual integrity and therefore warrants examination of functional correlates. Rinaldi, Simon; Bennett, David L H This review summarizes the major recent developments in understanding of pathogenic mechanisms in inflammatory and paraproteinaemic neuropathies. In the inflammatory neuropathies, there has been a particular focus on antibody-mediated disease affecting the nodal/paranodal regions. Disruption of electrical integrity at these sites on the axonal membrane can cause conduction block without other electrophysiological features of demyelination, which has led to calls for a revision in the classification of axonal versus demyelinating neuropathies to include the new category of 'nodo-paranodopathies'. There has likewise been an expansion in knowledge regarding the diverse disease mechanisms of the paraproteinaemic neuropathies. These also include disease mediated by antibodies binding to peripheral nerve antigens, but additionally encompass immune complex deposition, cellular infiltration, and cytokine production. An increasing range of laboratory tests for antibodies, growth factors, and cytokines are proposed as useful in the management of inflammatory and paraproteinaemic neuropathies. Furthermore, the traditional electrodiagnostic classification into axonal and demyelinating neuropathy may not always accurately reflect the underlying disease process. Understanding how these paraclinical tests aid in identifying the underlying disease has relevance to the practising clinician both in terms of diagnosis and for the selection of rational treatments. Ferrari, Luiz F; Levine, Jon D A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important co-morbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC; 50 mg/kg) neuropathy was mitochondrial-dependent and PKCε-independent, and alcohol-induced painful neuropathy was PKCε-dependent and mitochondrial-independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for 1 week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial-dependent but PKCε-independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction. Pourmohammadi, Nasir; Alimoradi, Houman; Mehr, Shahram Ejtemaei; Hassanzadeh, Gholamreza; Hadian, Mohammad Reza; Sharifzadeh, Mohammad; Bakhtiarian, Azam; Dehpour, Ahmad Reza As a cancer chemotherapeutic agent, paclitaxel (Taxol® ) causes dose-related peripheral neuropathy in human beings. The mechanisms underlying this toxicity are currently unknown, and there are no validated treatments for its prevention or control. To assess whether lithium as a pre-treatment and at subtherapeutic dose could prevent the peripheral neuropathy produced by it, rats were treated with paclitaxel (2 mg/kg i.p. every other day for a total of 16 times) and/or lithium chloride (300 mg/l) via water supply. General toxicity and body-weight were measured regularly during the experiment. To evaluate the sensory and motor neuropathy hot-plate, open-field test and nerve conduction velocity were used. In rats treated with only paclitaxel, there was behavioural, electrophysiological and histological evidence of a mixed sensorimotor neuropathy after 16 injections. Lithium robustly reduced the rate of mortality and general toxicity. Paclitaxel-induced sensorimotor neuropathy was significantly improved as indicated by changes in hotplate latency, total distance moved and a significant increase in sciatic, sural and tail sensory or motor nerve conduction velocity. The same results were observed in histopathological examinations; however, dorsal root ganglion neurons did not significantly change in the paclitaxel-treated groups. These results suggest that lithium, at subtherapeutic doses, can prevent both motor and sensory components of paclitaxel neuropathy in rats. Thus, lithium at these doses, as an inexpensive and relatively safe salt, may be useful clinically in preventing the neuropathy induced by paclitaxel treatment. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society. Yorek, Mark Anthony Peripheral neuropathy affects about 50% of the diabetic population. The manifestations range from pain, numbness, paresthesia and ulceration in the extremities and it is the major cause of non-traumatic amputations. Currently there is no effective treatment for peripheral neuropathy. With the prevalence of obesity and type 2 diabetes and associated complications reaching epidemic levels there is a critical need for finding a treatment to preserve nerve function. This article will review the potential for fish oil as a treatment for diabetic peripheral neuropathy. A through search of the PubMed database was performed and relevant articles on the topic were included in this review. Many studies support a role for fish oil in cardiovascular health. However, less information is available regarding the effect of fish oil on diabetes complications including neuropathy. Pre-clinical studies from my laboratory using diabetic rodent models have demonstrated that fish oil can slow progression and reverse diabetic neuropathy as determined by examining multiple endpoints. Mechanistically fish oil has been shown to have anti-inflammatory properties. Lowering the omega-6/omega-3 fatty acid ratio has been shown to be anti-thrombotic. Moreover, metabolites of eicosapentaenoic and docosahexaenoic acids, the main polyunsaturated fatty acids found in fish oil, commonly referred to as resolvins and neuroprotectin have been shown to be neuroprotective and can stimulate neuron outgrowth in vitro. Additional studies are required but existing data suggests that dietary enrichment with omega-3 fatty acids contained in fish oil may be beneficial treatment for diabetic neuropathy. Copyright© Bentham Science Publishers; For any queries, please email at [email protected]. Komatsu, Masaaki; Wheeler, Heather E.; Chung, Suyoun; Low, Siew-Kee; Wing, Claudia; Delaney, Shannon M.; Gorsic, Lidija K.; Takahashi, Atsushi; Kubo, Michiaki; Kroetz, Deanna L.; Zhang, Wei; Nakamura, Yusuke; Dolan, M. Eileen Purpose Paclitaxel is used worldwide in the treatment of breast, lung, ovarian and other cancers. Sensory peripheral neuropathy is an associated adverse effect that cannot be predicted, prevented or mitigated. To better understand the contribution of germline genetic variation to paclitaxel-induced peripheral neuropathy, we undertook an integrative approach that combines genome-wide association study (GWAS) data generated from HapMap lymphoblastoid cell lines (LCLs) and Asian patients. Methods GWAS was performed with paclitaxel-induced cytotoxicity generated in 363 LCLs and with paclitaxel-induced neuropathy from 145 Asian patients. A gene-based approach was used to identify overlapping genes and compare to a European clinical cohort of paclitaxel-induced neuropathy. Neurons derived from human induced pluripotent stem cells were used for functional validation of candidate genes. Results SNPs near AIPL1 were significantly associated with paclitaxel-induced cytotoxicity in Asian LCLs (P < 10−6). Decreased expression of AIPL1 resulted in decreased sensitivity of neurons to paclitaxel by inducing neurite morphological changes as measured by increased relative total outgrowth, number of processes and mean process length. Using a gene-based analysis, there were 32 genes that overlapped between Asian LCL cytotoxicity and Asian patient neuropathy (P < 0.05) including BCR. Upon BCR knockdown, there was an increase in neuronal sensitivity to paclitaxel as measured by neurite morphological characteristics. Conclusion We identified genetic variants associated with Asian paclitaxel-induced cytotoxicity and functionally validated the AIPL1 and BCR in a neuronal cell model. Furthermore, the integrative pharmacogenomics approach of LCL/patient GWAS may help prioritize target genes associated with chemotherapeutic-induced peripheral neuropathy. PMID:26015512 Komatsu, Masaaki; Wheeler, Heather E; Chung, Suyoun; Low, Siew-Kee; Wing, Claudia; Delaney, Shannon M; Gorsic, Lidija K; Takahashi, Atsushi; Kubo, Michiaki; Kroetz, Deanna L; Zhang, Wei; Nakamura, Yusuke; Dolan, M Eileen Paclitaxel is used worldwide in the treatment of breast, lung, ovarian, and other cancers. Sensory peripheral neuropathy is an associated adverse effect that cannot be predicted, prevented, or mitigated. To better understand the contribution of germline genetic variation to paclitaxel-induced peripheral neuropathy, we undertook an integrative approach that combines genome-wide association study (GWAS) data generated from HapMap lymphoblastoid cell lines (LCL) and Asian patients. GWAS was performed with paclitaxel-induced cytotoxicity generated in 363 LCLs and with paclitaxel-induced neuropathy from 145 Asian patients. A gene-based approach was used to identify overlapping genes and compare with a European clinical cohort of paclitaxel-induced neuropathy. Neurons derived from human-induced pluripotent stem cells were used for functional validation of candidate genes. SNPs near AIPL1 were significantly associated with paclitaxel-induced cytotoxicity in Asian LCLs (P < 10(-6)). Decreased expression of AIPL1 resulted in decreased sensitivity of neurons to paclitaxel by inducing neurite morphologic changes as measured by increased relative total outgrowth, number of processes and mean process length. Using a gene-based analysis, there were 32 genes that overlapped between Asian LCL cytotoxicity and Asian patient neuropathy (P < 0.05), including BCR. Upon BCR knockdown, there was an increase in neuronal sensitivity to paclitaxel as measured by neurite morphologic characteristics. We identified genetic variants associated with Asian paclitaxel-induced cytotoxicity and functionally validated the AIPL1 and BCR in a neuronal cell model. Furthermore, the integrative pharmacogenomics approach of LCL/patient GWAS may help prioritize target genes associated with chemotherapeutic-induced peripheral neuropathy. ©2015 American Association for Cancer Research. Bailey, Anne; Wingard, Deborah; Allison, Matthew; Summers, Priscilla; Calac, Daniel Diabetic peripheral neuropathy (DPN) develops in 30% of type 2 diabetes patients, increases the risk for foot ulcers and amputation, and is a significant source of disability and medical costs. Treatment remains challenging, propelling research to focus on therapeutic methods that aim to improve blood circulation or ameliorate oxidative stress that drives development of DPN. The aim of this study was to assess the effectiveness of acupuncture treatment for DPN symptoms and lower extremity arterial circulation in people with type 2 diabetes. Twenty-five patients seen at a Southern California Tribal Health Center who reported a threshold level of diabetic neuropathy symptoms in the lower extremities during the previous 4 weeks received acupuncture treatment once per week over a 10-week period between 2011 and 2013. The Neuropathy Total Symptom Scale (NTSS-6), Neuropathy Disability Score (NDS), and laser Doppler fluxmetry (LDF) were used for assessment at baseline and 10 weeks. A total of 19 of 25 study participants completed the study and reported a significant reduction in the NTSS symptoms of aching pain, burning pain, prickling sensation, numbness, and allodynia. Lancinating pain did not decrease significantly. LDF measures improved but not significantly. Acupuncture may effectively ameliorate selected DPN symptoms in these American Indian patients. Copyright © 2017 Medical Association of Pharmacopuncture Institute. Published by Elsevier B.V. All rights reserved. Botez, Stephan A; Herrmann, David N The present review focuses on recent developments in diagnosis and treatment of sensory neuropathies. It does not seek to establish a comprehensive classification of sensory neuropathies, nor treatment guidelines per se. Diagnostic criteria and guidelines have been developed for distal symmetric polyneuropathies, small fiber sensory neuropathies and sensory neuronopathies. Novel diagnostic tools such as skin biopsies now allow diagnosis of small fiber sensory neuropathies. Genetic testing has defined new subtypes of mitochondrial neuropathies and inherited neuropathies with sensory involvement. Intravenous immunoglobulin and tumor necrosis factor-alpha inhibitors show promise for some dysimmune sensory neuropathies or neuronopathies. Additional options for management of neuropathic pain are emerging. Diagnostic methods for both acquired and hereditary sensory neuropathies have progressed in recent years, leading to earlier and more specific diagnoses and a better understanding of disease mechanisms. Much progress remains to be made regarding symptomatic and disease-modifying therapy for a range of sensory neuropathies, including those due to diabetes, HIV infection and from dysimmune or hereditary causes. Höke, Ahmet; Ray, Mitali Peripheral neuropathy is a common and dose-limiting side effect of many chemotherapeutic drugs. These include platinum compounds, taxanes, vinca alkaloids, proteasome inhibitors, and others such as thalidomide and suramin. Although many rodent models have been developed using either mice or rats, there is limited consistency in the dose or mode of delivery of the drug; the sex, age, and genetic background of the animal used in the study; and the outcome measures used in evaluation of the peripheral neuropathy. Behavioral assays are commonly used to evaluate evoked sensory responses but are unlikely to be a good representation of the spontaneous sensory paresthesias that the patients experience. Electrophysiologic tests evaluate the integrity of large myelinated populations and are useful in drugs that cause either demyelination or degeneration of large myelinated axons but are insensitive to degeneration of unmyelinated axons in early stages of neuropathy. Histopathologic tools offer an unbiased way to evaluate the degree of axonal degeneration or changes in neuronal cell body but are often time consuming and require processing of the tissue after the study is completed. Nevertheless, use of drug doses and mode of delivery that are relevant to the clinical protocols and use of outcome measures that are both sensitive and objective in evaluation of the length-dependent distal axonal degeneration seen in most chemotherapy-induced peripheral neuropathies may improve the translational utility of these rodent models. Köşkderelioğlu, Aslı; Ortan, Pınar; Ari, Alpay; Gedizlioğlu, Muhteşem To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients with hepatitis C. The results were in KÖŞKDERELİOĞLU, Aslı; ORTAN, Pınar; ARI, Alpay; GEDİZLİOĞLU, Muhteşem Introduction To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. Methods Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. Results Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. Conclusion Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients Quintyne, K I; Mainstone, P; McNamara, B; Boers, P; Wallis, F; Gupta, R K The authors herein report the case of a 35-year-old woman undergoing adjuvant therapy for node positive breast cancer, who presented with short and rapidly progressive history of bilateral lower limb symptoms of peripheral neuropathy following therapy with paclitaxel. MRI of her neural axis revealed no leptomeningeal enhancement or focal metastatic lesions. Neurophysiological tests favoured toxic sensory axonal polyneuropathy. She remains symptomatic following discontinuation of therapy 20 months ago, and is under review with pain management. He, Rui; Hu, Yanyun; Zeng, Hui; Zhao, Jun; Zhao, Jungong; Chai, Yimin; Lu, Fengdi; Liu, Fang; Jia, Weiping Vitamin D deficiency was reported to be associated with diabetic peripheral neuropathy. But the association in Chinese population and the screening value of vitamin D deficiency for diabetic peripheral neuropathy were unknown. A total of 861 patients with type 2 diabetes were recruited in this cross-sectional study. Vitamin D deficiency was defined as serum circulating 25-hydroxyvitamin D(25(OH)D) level < 20 ng/mL. Peripheral neuropathy was evaluated by neurological symptoms, neurological signs, neurothesiometer and electromyogram. The patients with diabetic peripheral neuropathy had significantly lower serum 25(OH)D concentration (15.59 ± 7.68 ng/mL) and higher prevalence of vitamin D deficiency (80%) than patients with signs of diabetic peripheral neuropathy (17.66 ± 7.50 ng/mL; 64.5%) and non-DPN patients (18.35 ± 6.60; 61.7%) (all p < 0.01). Spearman's correlation analysis showed that serum circulating 25(OH)D level was closely associated with DPN (r = 0.121) and signs of DPN (r = 0.111) (both p < 0.01). After adjusting for all potential confounders, VDD was still linked with increased risk of DPN [odds ratio 2.59 (1.48-4.53)] (p < 0.01). Logistical regression analysis further revealed that VDD was an independent risk factor for DPN (β = 0.88) (p < 0.01). Receiver operating characteristic analysis indicated that serum 25(OH)D < 17.22 ng/mL hinted the signs of DPN and serum 25(OH)D < 16.01 ng/mL predicted the occurrence of DPN (both p < 0.01). Vitamin D deficiency is an independent risk factor for diabetic peripheral neuropathy and may be a potential biomarker for peripheral neuropathy in Chinese patients with type 2 diabetes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd. Tumusiime, David Kabagema; Venter, Francois; Musenge, Eustasius; Stewart, Aimee The introduction of antiretroviral therapy (ART) has dramatically reduced the mortality rate of people living with HIV (PLHIV). However, complications of both HIV and ART, such as peripheral neuropathy currently affect PLHIV. The purpose of this study was to establish the prevalence of peripheral neuropathy of the lower extremity and, its association with demographic and health status, characteristics among people on ART in Rwanda. A cross sectional study was conducted among 507 women and men aged between 18 and 60 years, on ART, randomly selected from eight selected ART clinics in Rwanda. Brief Peripheral Neuropathy Screen was used to assess peripheral neuropathy. Peripheral neuropathy prevalence was 59% overall, mean age of the participants was 39.7 (±9.2) and a slightly older age was associated with peripheral neuropathy; [42(±9.2) vs 37 (±8.8) (p < 0.001)]. 78% of participants living in urban settings compared to 40% in rural settings reported peripheral neuropathy, 69% of participants with higher levels of education (secondary level and above) reported lower extremity neuropathy.The three factors were significantly associated with peripheral neuropathy in multivariable model analysis: older age [aOR = 1.1, 95% CI (1.0, 1.2), p < 0.001], primary education level [aOR = 0.6 95% Cl (0.3, 1.0), p = 0.04] and urban setting [aOR = 0.1, 95% CI (0.06, 0.3), p < 0.001], after adjusting for other factors. None of the health status characteristics namely; the level of CD4 cell count, duration of HIV infection and duration on ART, was independently associated with peripheral neuropathy. The prevalence of peripheral neuropathy among PLHIV on ART in Rwanda is high. It is unclear why urban setting has an effect on PN levels in this cross sectional study, but does suggest that unidentified social and lifestyles factors may have a role in subjective symptoms and objective signs, of PN. Sweitzer, S M; Pahl, J L; DeLeo, J A The development of painful peripheral neuropathy is a dose-limiting side effect of numerous cancer chemotherapeutic agents. The present study utilized a rodent model of vincristine-induced neuropathy to determine whether a glial modulating agent, propentofylline, could attenuate vincristine-induced mechanical allodynia. Intravenous vincristine administered on days 1 through 5 and days 8 through 11 produced mechanical allodynia using 2 and 12 g von Frey filaments. Lumbar spinal cord from animals on day 15 expressed mild bilateral microglial and astrocytic activation as compared to saline-treated animals. Daily intraperitoneal propentofylline at 10 mg/kg attenuated mechanical allodynia induced by vincristine administration. In addition, propentofylline was found to decrease spinal microglial and astrocytic activation on day 15. These data suggest that central glial cells may play an important role in the development of painful neuropathy following vincristine administration. Van Brakel, W H Leprosy causes a 'mononeuritis multiplex' of immunological origin that results in autonomic, sensory and motor neuropathy. When detected and treated early, primary impairments may be reversible. However, 11-51% of patients do not recover. In addition, 33-56% of newly registered patients already have clinically detectable impairments, often no longer amenable to drug treatment. Among new patients, 6-27% present with secondary impairments, such as wounds, contractures and shortening of digits. All patients with impairments should be taught methods to prevent further impairment and subsequent disability (POID). As the result of impairments, many people experience limitation of activities of daily living, which can be partially overcome with the help of assistive devices, training, and surgery. As a result of these limitations, because of visible impairments, or simply because of the diagnosis 'leprosy', many people are restricted in their participation in society. Many overcome activity limitations and participation restrictions without assistance, despite residual impairments. However, some require intervention, such as physical or occupational therapy, reconstructive surgery or temporary socioeconomic assistance. Information on these issues is not collected routinely, and the few tools that exist to measure the severity or extent of impairment have not been widely used, nor have they been used to generate cohort-based statistics. There are no agreed indicators for monitoring POID activities or rehabilitation interventions. Work in the general field of rehabilitation has resulted in the ICIDH-2, which provides a conceptual framework for rehabilitation and the entire area of 'consequences of health conditions'. Although experience to date is very limited, the conceptual framework appears appropriate to leprosy. Data on the prevalence and incidence of primary and secondary impairments have been reported from several countries, the link between impairments and activity MELLION, MICHELLE L.; NGUYEN, VANANH; TONG, MING; GILCHRIST, JAMES; DE LA MONTE, SUZANNE Introduction The aim of this work was to determine the effect of chronic alcohol exposure on peripheral nerves in a nutritionally balanced rat model of alcoholism. Methods Three different strains of adult male rats were pair-fed for 8 weeks with isocaloric liquid diets containing 0% or 37% ethanol. Nerve conduction studies (NCS) were performed. Peripheral nerve and muscle were examined histologically with morphometrics. Results Ethanol exposure significantly slowed velocity in tibial and fibular nerves, but not in the plantar nerve in all 3 strains. Studies of the sciatic nerve revealed decreased fiber diameters and increased regenerative sprouts in peripheral nerves. There was muscle denervation of ethanol-exposed rats in all 3 strains. Conclusions Chronic ethanol exposure caused a polyneuropathy characterized by axonal degeneration despite adequate nutrition. These results suggest that ethanol exposure has direct neurotoxic effects on peripheral nerves. This model may be useful in understanding the underlying mechanism(s) of alcohol-related peripheral neuropathy. PMID:23761140 Brunelli, Brian; Gorson, Kenneth C Complementary and alternative medicine (CAM) therapies have become increasingly popular and are used regularly by patients with chronic neurological disorders. The prevalence and characteristics of CAM use by patients with peripheral neuropathy is unknown. We performed a prospective, questionnaire-based study to determine the prevalence and patterns of use of CAM therapies in 180 consecutive outpatients with peripheral neuropathy. The use of CAM was reported by 77 patients (43%) with neuropathy. The most frequent were megavitamins (35%), magnets (30%), acupuncture (30%), herbal remedies (22%), and chiropractic manipulation (21%); 37 (48%) tried more than one form of alternative treatment. Seventeen respondents (27%) thought their neuropathy symptoms improved with these approaches. Those who used CAM were slightly younger (mean age 62 vs. 65 years, p = 0.05) and more often college educated (39% vs. 24%, p = 0.03) compared to CAM nonusers. They also more often reported burning neuropathic pain (62% vs. 44%, p = 0.01). Patients with diabetic neuropathy used CAM more frequently than others (p = 0.03). The most common reason for using CAM was inadequate pain control (32%). Almost half of patients did not consult a physician before starting CAM. We conclude that there is a high prevalence of CAM use in our patients with neuropathy, and one-quarter reported that their symptoms improved. CAM users were better educated than nonusers, but most did not discuss CAM treatments with their physician. Neuropathic pain was substantially more common in CAM users, and lack of pain control was the most common reason for CAM use. Guest, Maya; Attia, John R; D'este, Catherine A; Boggess, May M; Brown, Anthony M; Gibson, Richard E; Tavener, Meredith A; Ross, James; Gardner, Ian; Harrex, Warren This study aimed to examine possible persisting peripheral neuropathy in a group who undertook fuel tank repairs on F-111 aircraft, relative to two contemporaneous comparison groups. Vibration perception threshold (VPT) was tested using biothesiometry in 614 exposed personnel, compared with two unexposed groups (513 technical trades and 403 nontrades). Regression modeling was used to examine associations, adjusting for possible confounders. We observed that 26% of participants had chronic persistent increased VPT in the great toe. In contrast, statistically significant higher VPT of the great toe was observed in the comparison groups; however, the effect was small, about 1/4 the magnitude of diabetes. Age, height, and diabetes were all significant and strong predictors in most models. This study highlights chronic persisting peripheral neuropathy in a population of aircraft maintainers. Schloss, Janet; Colosimo, Maree The purpose of this mini review is to evaluate the literature on B vitamins and chemotherapy-induced peripheral neuropathy. One hundred and five journal articles were evaluated and nine manuscripts were included. There was one in vitro, one was an animal and seven were human studies. The in vitro study was a safety study on vitamin B6 and oxaliplatin which was not directly related to CIPN. The animal study evaluated vitamin B3 on paclitaxel administration with positive results. The human studies varied using a vitamin B complex, vitamin B12 only and vitamin B6. Chemotherapy-induced peripheral neuropathy (CIPN) continues to plague patients and the medical fraternity. Currently, there are still no conclusive protective or treatment options. B vitamins have been found to play a role in CIPN prevention, but further studies are required to ascertain possible protection and treatment options. Mora, Erika; Smith, Ellen M Lavoie; Donohoe, Clare; Hertz, Daniel L Vincristine is a chemotherapeutic agent that is a component of many combination regimens for a variety of malignancies, including several common pediatric tumors. Vincristine treatment is limited by a progressive sensorimotor peripheral neuropathy. Vincristine-induced peripheral neuropathy (VIPN) is particularly challenging to detect and monitor in pediatric patients, in whom the side effect can diminish long term quality of life. This review summarizes the current state of knowledge regarding VIPN, focusing on its description, assessment, prediction, prevention, and treatment. Significant progress has been made in our knowledge about VIPN incidence and progression, and tools have been developed that enable clinicians to reliably measure VIPN in pediatric patients. Despite these successes, little progress has been made in identifying clinically useful predictors of VIPN or in developing effective approaches for VIPN prevention or treatment in either pediatric or adult patients. Further research is needed to predict, prevent, and treat VIPN to maximize therapeutic benefit and avoid unnecessary toxicity from vincristine treatment. PMID:27904761 Rosewell, Alexander; Clark, Geoff; Mabong, Paul; Ropa, Berry; Posanai, Enoch; Man, Nicola W. Y.; Dutta, Samir R.; Wickramasinghe, Wasa; Qi, Lixia; Ng, Jack C.; Mola, Glen; Zwi, Anthony B.; MacIntyre, C. Raina Background In October 2004, Manam Island volcano in Papua New Guinea erupted, causing over 10 000 villagers to flee to internally displaced person (IDP) camps, including 550 from Dugulaba village. Following violence over land access in March 2010, the IDPs fled the camps, and four months later concurrent outbreaks of acute watery diarrhea and unusual neurological complaints were reported in this population. Materials and Methods A retrospective case-control study was conducted to identify the risk factors for peripheral neuropathy. Rectal swabs were collected from cases of acute watery diarrhea. Hair and serum metals and metalloids were analyzed by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Results There were 17 deaths among the 550 village inhabitants during the outbreak period at a crude mortality rate 21-fold that of a humanitarian crisis. Vibrio cholerae O1 El Tor Ogawa was confirmed among the population. Access to community-level rehydration was crucial to mortality. Peripheral neuropathy was diagnosed among cases with neurological symptoms. A balanced diet was significantly protective against neuropathy. A dose-response relationship was seen between peripheral neuropathy and a decreasing number of micronutrient- rich foods in the diet. Deficiencies in copper, iron, selenium and zinc were identified among the cases of peripheral neuropathy. Conclusions Cholera likely caused the mostly preventable excess mortality. Peripheral neuropathy was not caused by cholera, but cholera may worsen existing nutritional deficiencies. The peripheral neuropathy was likely caused by complex micronutrient deficiencies linked to non-diversified diets that potentially increased the vulnerability of this population, however a new zinc-associated neuropathy could not be ruled out. Reoccurrence can be prevented by addressing the root cause of displacement and ensuring access to arable land and timely resettlement. PMID:24023752 Pacitto, Alessandra; Paglino, Alessandra; Di Genova, Lorenza; Leonardi, Alberto; Farinelli, Edoardo; Principi, Nicola; di Cara, Giuseppe; Esposito, Susanna Background: Clinically relevant neurological manifestations in children with celiac disease (CD) are unusual, especially when they are considered as signs of the onset of the disease. In this paper, a case of Guillain-Barrè syndrome (GBS) as the first manifestation of CD in a 23-month-old child is reported. Case presentation: We describe a case of CD onset with peripheral neuropathy in a 23-month-old Bulgarian boy presenting with a sudden refusal to walk and absence of deep tendon reflexes in both lower limbs. Neurological symptoms were preceded by two months of gastrointestinal symptoms such as vomiting, abdominal distention, and clear signs of malnutrition and weight loss. When we evaluated the child six months after the onset of the symptoms, clinical and laboratory findings showed clear signs of peripheral neuropathy associated with malnutrition. Serum deamidated gliadin and tissue transglutaminase antibodies were therefore measured. The anti-gliadin levels were more than sixteen times higher than normal and the IgA anti-transglutaminase levels were four times higher than normal. Anti-endomysium antibodies were positive, and human leukocyte antigens (HLA) II typing confirmed a genetic predisposition to CD (DQ2 positive and DQ8 negative). Given the association between the clinical evidence of the disease and the results of the celiac screening tests, a diagnosis of CD was made without biopsy confirmation of the enteropathy. The child began a restricted gluten-free diet that led to complete recovery of the peripheral neuropathy, walking, reflexes, and overall improvement after three months on the diet. Conclusion: Our case underlines the rare but possible associations between CD and peripheral neuropathy in children as an onset symptom, even in the absence of gastrointestinal manifestations, thus suggesting that CD should always be considered in the differential diagnosis of peripheral neuropathy in children. A good knowledge of the extra Pacitto, Alessandra; Paglino, Alessandra; Di Genova, Lorenza; Leonardi, Alberto; Farinelli, Edoardo; Principi, Nicola; di Cara, Giuseppe Background: Clinically relevant neurological manifestations in children with celiac disease (CD) are unusual, especially when they are considered as signs of the onset of the disease. In this paper, a case of Guillain-Barrè syndrome (GBS) as the first manifestation of CD in a 23-month-old child is reported. Case presentation: We describe a case of CD onset with peripheral neuropathy in a 23-month-old Bulgarian boy presenting with a sudden refusal to walk and absence of deep tendon reflexes in both lower limbs. Neurological symptoms were preceded by two months of gastrointestinal symptoms such as vomiting, abdominal distention, and clear signs of malnutrition and weight loss. When we evaluated the child six months after the onset of the symptoms, clinical and laboratory findings showed clear signs of peripheral neuropathy associated with malnutrition. Serum deamidated gliadin and tissue transglutaminase antibodies were therefore measured. The anti-gliadin levels were more than sixteen times higher than normal and the IgA anti-transglutaminase levels were four times higher than normal. Anti-endomysium antibodies were positive, and human leukocyte antigens (HLA) II typing confirmed a genetic predisposition to CD (DQ2 positive and DQ8 negative). Given the association between the clinical evidence of the disease and the results of the celiac screening tests, a diagnosis of CD was made without biopsy confirmation of the enteropathy. The child began a restricted gluten-free diet that led to complete recovery of the peripheral neuropathy, walking, reflexes, and overall improvement after three months on the diet. Conclusion: Our case underlines the rare but possible associations between CD and peripheral neuropathy in children as an onset symptom, even in the absence of gastrointestinal manifestations, thus suggesting that CD should always be considered in the differential diagnosis of peripheral neuropathy in children. A good knowledge of the extra Advances in supportive care have increased the likelihood that previously less common adverse effects of chemotherapy will be more evident. The incidence of chemotherapy-induced peripheral neuropathy (CIPN) is increasing because more neurotoxic drugs have been developed and because patients are living longer and receiving multiple chemotherapy regimens. This article reviews the anatomy of the peripheral nervous system, the proposed mechanisms of CIPN, and manifestations of CIPN from vinca alkaloids, taxanes, and platinum analogs. Major topics of this article are evidence-based data regarding symptom management, a review of medical management, and a synthesis of nursing care for patients at risk for or experiencing CIPN. Chua, K C; Kroetz, D L Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity experienced in 30-40% of patients undergoing treatment with various chemotherapeutics, including taxanes, vinca alkaloids, epothilones, proteasome inhibitors, and thalidomide. Importantly, CIPN significantly affects a patient's quality of life. Recent genetic association studies are enhancing our understanding of CIPN pathophysiology and serve as a foundation for identification of genetic biomarkers to predict toxicity risk and for the development of novel strategies for prevention and treatment. Cohen, Helen S.; Mulavara, Ajitkumar P.; Peters, Brian T.; Sangi-Haghpeykar, Haleh; Kung, Doris H.; Mosier, Dennis R.; Bloomberg, Jacob J. Objective Few tests of functional motor behavior are useful for rapidly screening people for lower extremity peripheral neuropathy. The goal of this study was to improve the widely used Tandem Walking test (TW). Methods We tested adult normals and ambulatory peripheral neuropathy patients (PN) with eyes open and eyes closed, while they performed TW on industrial carpeting, in sock-covered feet. Each subject wore a torso-mounted inertial motion unit to measure kinematic data. PN subjects’ data were also compared to historical data on patients with vestibular impairments (VI). Results The normal and PN groups differed significantly on TW on the number of steps completed. PN and VI data also differed significantly on both visual conditions. Kinematic data showed that PN patients were more unstable than normals. For the number of steps taken during the eyes open condition receiver operating characteristic (ROC) values were only 0.81. For the number of steps taken during the eyes closed condition, however, ROC=0.88. Although not optimal, this ROC value is better. Sensitivity and specificity at a cut-off of 2 steps were 0.81 and 0.92, respectively, and at a cut-off of 3 steps was 0.86 and 0.75, respectively. ROC values for kinematic data were all < 0.8 and, when combined with the ROC value for the number of steps, the total ROC value did not improve appreciably. Conclusions Although not ideal for screening patients who may have peripheral neuropathy, counting the number of steps during TW is a quick and useful clinical test. TW is most sensitive to peripheral neuropathy patients when they are tested with eyes closed. PMID:24096950 Levade, T; Graber, D; Flurin, V; Delisle, M B; Pieraggi, M T; Testut, M F; Carrière, J P; Salvayre, R Human beta-mannosidosis is an inherited lysosomal storage disorder described in only seven families. We present a further case in a black African 14-year-old boy with severely deficient beta-mannosidase activity, bilateral thenar and hypothenar amyotrophy, electrophysiologically demonstrable demyelinating peripheral neuropathy, and cytoplasmic vacuolation of skin fibroblasts and lymphoid cells. The clinical and biochemical features of our patient are compared to those of previously reported patients. Kindstrand, E; Nilsson, B Y; Hovmark, A; Pirskanen, R; Asbrink, E Forty-seven patients with the late borrelial manifestation acrodermatitis chronica atrophicans (ACA) and with objective neurological and/or neurophysiological findings were followed up after antibiotic treatment with dermatological, serological, neurological and neurophysiological controls. Despite a good therapeutic effect on ACA lesions, specific antibody values and symptoms of irritative nerve lesions, the objective neurological and neurophysiological findings of nerve deficit remained unchanged. There was no progress of neuropathy findings during the follow-up time. Our interpretation of the results is that the remaining neuropathy signs after treatment of ACA are neurological sequelae and not manifestations of persisting Borrelia infection. Calcutt, Nigel A; Smith, Darrell R; Frizzi, Katie; Sabbir, Mohammad Golam; Chowdhury, Subir K Roy; Mixcoatl-Zecuatl, Teresa; Saleh, Ali; Muttalib, Nabeel; Van der Ploeg, Randy; Ochoa, Joseline; Gopaul, Allison; Tessler, Lori; Wess, Jürgen; Jolivalt, Corinne G; Fernyhough, Paul Sensory neurons have the capacity to produce, release, and respond to acetylcholine (ACh), but the functional role of cholinergic systems in adult mammalian peripheral sensory nerves has not been established. Here, we have reported that neurite outgrowth from adult sensory neurons that were maintained under subsaturating neurotrophic factor conditions operates under cholinergic constraint that is mediated by muscarinic receptor-dependent regulation of mitochondrial function via AMPK. Sensory neurons from mice lacking the muscarinic ACh type 1 receptor (M1R) exhibited enhanced neurite outgrowth, confirming the role of M1R in tonic suppression of axonal plasticity. M1R-deficient mice made diabetic with streptozotocin were protected from physiological and structural indices of sensory neuropathy. Pharmacological blockade of M1R using specific or selective antagonists, pirenzepine, VU0255035, or muscarinic toxin 7 (MT7) activated AMPK and overcame diabetes-induced mitochondrial dysfunction in vitro and in vivo. These antimuscarinic drugs prevented or reversed indices of peripheral neuropathy, such as depletion of sensory nerve terminals, thermal hypoalgesia, and nerve conduction slowing in diverse rodent models of diabetes. Pirenzepine and MT7 also prevented peripheral neuropathy induced by the chemotherapeutic agents dichloroacetate and paclitaxel or HIV envelope protein gp120. As a variety of antimuscarinic drugs are approved for clinical use against other conditions, prompt translation of this therapeutic approach to clinical trials is feasible. Istenes, Ildikó; Nagy, Zsolt; Demeter, Judit Longer remissions and better overall survival rates can be achieved with the introduction of new, effective treatments and targeted therapies in the past 1-2 decades, however, the incidence of side effects is also increasing parallelly. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially debilitating side effect due to peripheral somatic or autonomic nerve dysfunction. CIPN becomes increasingly important, as it affects patients' quality of life, and it is very often a dose limiting factor with the potential for reduced treatment efficacy. The pathomechanism, diagnosis, prevention and treatment possibilities are described in this review with special attention to the different groups of drugs. Xianbin, Wang; Mingyu, Wang; Dong, Xu; Huiying, Li; Yan, Xu; Fengchun, Zhang; Xiaofeng, Zeng Abstract This article aims to analyze the frequency and clinical characteristics of peripheral neuropathy (PN) in patients with systemic lupus erythematosus (SLE). A total of 4924 SLE patients admitted to the Peking Union Medical College Hospital, Beijing, China, from January 1995 to September 2013 were included in this retrospective analysis. The individuals designated as control patients were selected from the pool of SLE patients without PN using the systematic sampling method of 1:2 during the same time. The prevalence of SLE-associated PN (SLE-PN) in SLE patients was 1.5% (73/4924). Seventy-nine cases of PN affected 73 patients and 6 of these patients (8.2%) presented with 2 types of PN. Among the 7 types of PN, polyneuropathy was the most frequent and was diagnosed in 47 cases (59.5%); the remaining patients suffered from mononeuropathy (13.9%), cranial neuropathy (12.7%), myasthenia gravis (10.1%), autonomic neuropathy (2.5%), or acute inflammatory demyelinating polyradiculoneuropathy (1.3%). Five patients developed PN before the onset of SLE (3 out of 5 patients had myasthenia gravis). The most common PN-related symptoms were myasthenia and numbness (50.6%), followed by pain in affected regions (35.9%). PN symptoms were relieved in a majority of the patients (76.7%) after treatment. Compared with non-SLE-PN patients, patients with SLE-PN had a higher frequency of fever (65.8% vs 45.9%, P < 0.01), mucocutaneous involvement (73.9% vs 36.3%, P < 0.01), arthritis (42.5% vs 28.1%, P < 0.05), myositis (17.8% vs 5.5%, P < 0.01), and central nervous system involvement (38.4% vs 21.9%, P < 0.05) as well as being positive for the anti-Sm antibody (31.4% vs 18.8%), immunoglobulin G (IgG) elevation (53.6% vs 37.1%, P < 0.01), and reduction in complement 3 (54.8% vs 36.9%, P < 0.05). A statistically significant difference was found between the Systemic Lupus Erythematosus Disease Activity Index scores in SLE-PN patients compared with the non Liu, L Z; Wu, J Y; Wu, Z Y; Chen, Z H; Ling, L; Sun, B; Li, Y F; Huang, X S To identify the sensitive scales and the early change of nerve conduction for chronic oxaliplatin-induced peripheral neuropathy (OXLIPN), and to investigate correlation between the symptoms of acute OXLIPN and chronic OXLIPN. Between December 2014 and August 2015, 16 colorectal cancer patients confirmed by pathology, from department of Oncology, Chinese PLA General Hospital, scheduled to receive XELOX, completed the acute neurotoxic symptoms questionnaire at the end of 1 cycles and the scales of TNSc and NCI-CTC at the baseline and the end of 4 cycles. Nerve conduction studies (bilateral peroneal nerves and sural nerves) were performed in 11 patients at the baseline and the end of 4 cycles. After chemotherapy, TNSc increased 1-9 points for all cases, while NCI-CTC increased 1 point for only 9 cases, the remaining 7 cases had the same NCI-CTC score before and after chemotherapy, where TNSc increased 1-6 points. Left sural nerve a-SNAP (amplitude of sensory nerve action potential) was (15.3±5.8)μV before chemotherapy and(12.3±5.0)μV after chemotherapy. Right sural nerve a-SNAP was (17.4±8.6)μV before chemotherapy and (13.3±6.7)μV after chemotherapy. After chemotherapy, these datum were significantly reduced for left peroneal nerve distal and proximal a-CMAP (amplitude of compound muscle action potential), bilateral sural nerve a-SNAP and left sural nerve SCV (sensory conduction velocity) (P<0.05). After chemotherapy, TNSc was correlated significantly with the acute neurotoxic symptoms questionnaire (Spearman r=0.698, P=0.003). TNSc is more sensitive to the severity and changes in chronic OXLIPN than NCI-CTC. Sural nerve a-SNAP has a higher sensitivity for the early changes of nerve conduction studies in chronic OXLIPN. Patients who have more symptoms of acute OXLIPN are those who eventually develop more severe chronic OXLIPN. Improvement of therapeutic strategies for peripheral neuropathies requires multicentric clinical trials. For chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a randomized controlled multicentric study compared IgIV to pulses of methylprednisolone (MP) given for 6 months. The primary endpoint was treatment discontinuation due to inefficacy or intolerance; 45 patients were enrolled: more patients had interrupted MP than IVIg, usually because of inefficacy. A multicentric randomized clinical trial (PREDICT) evaluated long-term remission of CIDP after short-term corticosteroid therapy (pulses of dexamethasone or prednisolone); 39 patients were enrolled: 26% achieved cure or remission, a relapse occurred in 50% after a delay of 11 to 17 months. Differential diagnosis was identified in 58% of patients who had not responded to any therapy. For refractory CIDP, a retrospective study showed the possibility of functional improvement in 24% of cases after adjunction of an immunomodulatory agent; cyclosporine was associated with the highest rate of adverse events or side effects. In familial amyloidotic polyneuropathy, a multicentric controlled study against placebo with tafamidis, an akinetic stabilizer of transthyretin (TTR) 20mg/d, in early stage of Val30MetTTR showed efficiency in the evaluable group and led to marketing authorization by the EMA in stage 1 to slow the progression of the neuropathy. A Cochrane database system review showed that there are no randomized or quasi-randomized controlled clinical trials of treatment for POEMS syndrome, for neuropathies with anti-MAG antibodies, or multifocal motor neuropathy on which to base practice. This review underlines the usefulness of multicentric randomized trials to assess treatments in peripheral neuropathies. Copyright © 2013 Elsevier Masson SAS. All rights reserved. Biasiotta, A; Casato, M; La Cesa, S; Colantuono, S; Di Stefano, G; Leone, C; Carlesimo, M; Piroso, S; Cruccu, G; Truini, A Hepatitis C virus (HCV)-related cryoglobulinemia commonly causes disabling complications including peripheral neuropathy and neuropathic pain. In this prospective clinical, neurophysiological, and skin biopsy study we aimed at assessing clinical characteristics and risk factors of peripheral neuropathy and neuropathic pain in patients with HCV-related cryoglobulinemia. We enrolled 69 consecutive patients with HCV-related cryoglobulinemia. We diagnosed neuropathic pain with the DN4 (Neuropathic Pain Diagnostic) questionnaire, and rated the various neuropathic pains with the Neuropathic Pain Symptom Inventory (NPSI). All patients underwent a standard nerve conduction study to assess Aβ-fiber function, laser-evoked potentials to assess Aδ-fiber function, and skin biopsy to assess C-fiber terminals. Of the 69 patients studied, 47 had a peripheral neuropathy, and 29 had neuropathic pain. Patients with peripheral neuropathy were older than those without (P < 0.0001). While peripheral neuropathy was significantly associated with the duration of HCV infection (P < 0.01), it was unrelated to the duration of cryoglobulinemia and cryocrit (P > 0.5). The severity of peripheral neuropathy significantly correlated with the duration of HCV infection (P < 0.05). Laser-evoked potential amplitudes were significantly lower in patients with than in those without neuropathic pain (P < 0.05). Conversely, no difference was found in nerve conduction study and skin biopsy findings (P > 0.05). Our findings show that peripheral neuropathy is related to age and HCV infection, rather than to cryoglobulinemia, and neuropathic pain is associated with damage to nociceptive pathways as assessed with laser-evoked potentials; this might be useful for designing more effective clinical interventions for these common HCV related-cryoglobulinemia complications. Nihei, Satoru; Sato, Junya; Kashiwaba, Masahiro; Itabashi, Tetsuya; Kudo, Kenzo; Takahashi, Katsuo This study included patients who were prescribed pregabalin, vitamin B12, amitriptyline, clonazepam, or carbamazepine to improve oxaliplatin(L-OHP)- or paclitaxel(PTX)-induced peripheral neuropathy at Iwate Medical University Hospital between April 2011 and July 2012. The efficacy and safety of pregabalin was evaluated by comparing 27 patients with L-OHP-induced peripheral neuropathy and 28 with PTX-induced peripheral neuropathy prescribed pregabalin(pregabalin group) with 20 patients with L-OHP-induced peripheral neuropathy and 25 with PTX-induced peripheral neuropathy prescribed other drugs(non-pregabalin group). Response was defined as a decrease in neuropathy of at least 1 grade from baseline. The response rates were 40.7% and 10.0% for L-OHP-induced peripheral neuropathy patients and 28.6% and 12.0% for PTX-induced peripheral neuropathy patients in the pregabalin and non-pregabalin groups, respectively. The severity of peripheral neuropathy before and after the administration of pregabalin differed significantly[L-OHP, 1.33±0.48(mean±SD) vs. 1.00±0.78 and PTX, 1.46±0.69 vs. 1.21±0.88]. In 28-37% of patients, pregabalin was associated with adverse events, with drowsiness and dizziness being frequently observed. In conclusion, pregabalin was efficacious in reducing the severity of L-OHP- and PTX-induced peripheral neuropathy. Abuaisha, B B; Costanzi, J B; Boulton, A J Forty-six diabetic patients with chronic painful peripheral neuropathy were treated with acupuncture analgesia to determine its efficacy and long-term effectiveness. Twenty-nine (63%) patients were already on standard medical treatment for painful neuropathy. Patients initially received up to six courses of classical acupuncture analgesia over a period of 10 weeks, using traditional Chinese Medicine acupuncture points. Forty-four patients completed the study with 34 (77%) showing significant improvement in their primary and/or secondary symptoms (P < 0.01). These patients were followed up for a period of 18-52 weeks with 67% were able to stop or reduce their medications significantly. During the follow-up period only eight (24%) patients required further acupuncture treatment. Although 34 (77%) patients noted significant improvement in their symptoms, only seven (21%) noted that their symptoms cleared completely. All the patients but one finished the full course of acupuncture treatment without reported or observed side effects. There were no significant changes either in the peripheral neurological examination scores, VPT or in HbA1c during the course of treatment. These data suggest that acupuncture is a safe and effective therapy for the long-term management of painful diabetic neuropathy, although its mechanism of action remains speculative. Hopf, H C Acrodermatitis chronica atrophicans is a dermatological condition that takes a chronically progressive course and finally leads to a widespread atrophy of the skin. Involvement of the peripheral nervous system is frequently observed, predominantly a sensory polyneuropathy. General reactions, the effect of penicillin treatment, the histological findings, and reports concerning a communicable agent transmittable from human to human as well in tissue cultures point to an infectious disease. Acrodermatitis chronica atrophicans follows a peculiar geographical distribution forming clusters of high prevalence in certain regions. Transmission by ticks is suggested. Images PMID:168318 Yian, Edward H; Dillon, Mark; Sodl, Jeff; Dionysian, Emil; Navarro, Ronald; Singh, Anshuman The incidence of post-operative compressive peripheral neuropathy (CPN) after shoulder arthroplasty is not known. We hypothesized that the likelihood following shoulder arthroplasty would be higher compared to a non-operative cohort. Retrospective study compared the incidence of symptomatic CPN after shoulder replacement to a 1:1 age- and gender-matched non-operative control group with shoulder arthritis. Six hundred six consecutive shoulder replacements from a regional shoulder arthroplasty registry were analyzed. This included 319 primary total shoulder arthroplasties (TSR), 168 hemiarthroplasties (HA), 31 humeral resurfacings (HHR), 71 reverse arthroplasties (RTSA), and 17 revision arthroplasties. Diagnosis of post-operative CPN was obtained by documented clinical examination by a physician consistent with CPN based on patient complaints, positive nerve study results, and/or nerve decompression. Age, gender, body mass index, diabetes status, thyroid abnormalities, operative side, and anesthesiology (ASA) score were examined. The surgery group had 15 cases (2.5 %) of post-operative CPN (ten carpal tunnel syndrome, five cubital tunnel syndrome). This included seven TSR, six HA, one revision TSR, and one RTSA. Diagnoses included ten osteoarthritis, four rotator cuff arthropathies, and one chondrolysis. Control group had eight cases (1.3 %) of CPN (seven carpal tunnel syndrome, one cubital tunnel syndrome). In univariate analysis, age, gender, body mass index, ASA score, operative side, thyroid status, and diabetes were not predictors of post-operative CPN. CPN incidence between surgical and control groups was not statistically significant. The 1-year incidence rate of new onset clinical post-operative CPN symptoms was 2.5 %. There was no significant difference of CPN rates between surgical and non-operative groups. Lebo, R.V.; Li, L.Y.; Flandermeyer, R.R. Peripheral myelin protein (PMP-22) gene aneuploidy results in Charcot-Marie-Tooth disease Type 1A (CMT1A) and the Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) in Japanese patients as well as Caucasian Americans. Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, results when expression of one of at least seven genes is defective. CMT1A, about half of all CMT mutations, is usually associated with a duplication spanning the peripheral myelin protein-22 gene on distal chromosome band 17p11.2. Autosomal dominant HNPP (hereditary pressure and sensory neuropathy, HPSN) results from a deletion of the CMT1A gene region. Multicolor in situ hybridization with PMP-22 gene region probe characterized HNPP deletion reliably and detected all different size duplications reported previously. In summary, 72% of 28 Japanese CMT1 (HMSNI) patients tested had the CMT1A duplication, while none of the CMT2 (HMSNII) or CMT3 (HMSNIII) patients had a duplication. Three cases of HNPP were identified by deletion of the CMT1A gene region on chromosome 17p. HNPP and CMT1A have been reported to result simultaneously from the same unequal recombination event. The lower frequency of HNPP compared to CMT1A suggests that HNPP patients have a lower reproductive fitness than CMT1A patients. This result, along with a CMT1A duplication found in an Asian Indian family, demonstrates the broad geographic distribution and high frequency of PMP-22 gene aneuploidy. Palmer, Shannon J; Hong, Junggi There has been rising interest in evaluating spinal reflex activity within the clinical population, however no study has yet investigated the reliability of presynaptic inhibition (PI) on patients with diabetic peripheral neuropathy (DPN). Because neuropathy is closely related to central nervous system modification, it is important to understand the mechanism of spinal reflex activity in the DPN population. Therefore, the purpose of the study was to evaluate the reliability of PI in patients with DPN. Eight participants (58.24 ± 6.38 yrs.) diagnosed with either type I or type II diabetes and peripheral neuropathy were recruited for the study. Each subject's H-reflex was measured using an EMG to elicit and record a series of 10 paired reflex depression trials. Reliability was measured by calculating Intra Class Correlation Coefficients (ICCs) with a 95% confidence interval. The results showed excellent reliability in both intraday (0.94) and interday (0.88) reliability. Therefore, analyzing PI in the central nervous system allows for an accurate evaluation of spinal cord circuitry in a non-invasive manner. Li, Sheyu; Chen, Xiang; Li, Qianrui; Du, Juan; Liu, Zhimin; Peng, Yongde; Xu, Mian; Li, Qifu; Lei, Minxiang; Wang, Changjiang; Zheng, Shaoxiong; Zhang, Xiaojuan; Yu, Hongling; Shi, Jinyu; Tao, Shibing; Feng, Ping; Tian, Haoming To assess the efficacy and safety of acetyl-L-carnitine (ALC) on diabetic peripheral neuropathy compared with methylcobalamin (MC). This was a multicenter, randomized, parallel-group, double-blind, double-dummy, positive-controlled, non-inferior phase II clinical trial. Diabetic patients with abnormal nerve conduction test results were randomized in a 1:1 ratio to receive oral ALC 500 mg t.i.d. or MC 0.5 mg t.i.d. for 24 weeks. The neuropathy symptom score, neuropathy disability score and neurophysiological parameters were measured during follow up. A total of 232 patients were randomized (ALC n = 117, MC n = 115), 88% of which completed the trial. At week 24, patients from both groups had significant reductions in both neuropathy symptom score and neuropathy disability score with no significant difference between two groups (neuropathy symptom score reduction: ALC vs MC 2.35 ± 2.23, P < 0.0001 vs 2.11 ± 2.48, P < 0.0001, intergroup P = 0.38; neuropathy disability score reduction ALC vs MC 1.66 ± 1.90, P < 0.0001 vs 1.35 ± 1.65, P < 0.0001, intergroup P = 0.23). Neurophysiological parameters were also improved in both groups. No significant difference was found between groups in the development of adverse events. ALC is as effective as MC in improving clinical symptoms and neurophysiological parameters for patients with diabetic peripheral neuropathy over a 24-week period with good tolerance. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. Wang, Hongli; Fan, Dongsheng; Zhang, Yingshuang Angiogenin is associated with the pathogenesis of diabetic peripheral neuropathy. Here, we quenced the coding region of the angiogenin gene in genomic DNA from 207 patients with type 2 diabetes mellitus (129 diabetic peripheral neuropathy patients and 78 diabetic non-neuropathy patients) and 268 healthy controls. All subjects were from the Han population of northern China. No mutations were found. We then compared the genotype and allele frequencies of the angiogenin synonymous single nucleotide polymorphism rs11701 between the diabetic peripheral neuropathy patients and controls, and between the diabetic neuropathy and non-neuropathy patients, using a case-control design. We detected no statistically significant genetic associations. Angiogenin may not be associated with genetic susceptibility to diabetic peripheral neuropathy in the Han population of northern China. Callaghan, Brian C; Price, Raymond S; Chen, Kevin S; Feldman, Eva L Peripheral neuropathy is a prevalent condition that usually warrants a thorough history and examination but has limited diagnostic evaluation. However, rare localizations of peripheral neuropathy often require more extensive diagnostic testing and different treatments. To describe rare localizations of peripheral neuropathy, including the appropriate diagnostic evaluation and available treatments. References were identified from PubMed searches conducted on May 29, 2015, with an emphasis on systematic reviews and randomized clinical trials. Articles were also identified through the use of the authors' own files. Search terms included common rare neuropathy localizations and their causes, as well as epidemiology, pathophysiology, diagnosis, and treatment. Diffuse, nonlength-dependent neuropathies, multiple mononeuropathies, polyradiculopathies, plexopathies, and radiculoplexus neuropathies are rare peripheral neuropathy localizations that often require extensive diagnostic testing. Atypical neuropathy features, such as acute/subacute onset, asymmetry, and/or motor predominant signs, are frequently present. The most common diffuse, nonlength-dependent neuropathies are Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and amyotrophic lateral sclerosis. Effective disease-modifying therapies exist for many diffuse, nonlength-dependent neuropathies including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and some paraprotein-associated demyelinating neuropathies. Vasculitic neuropathy (multiple mononeuropathy) also has efficacious treatment options, but definitive evidence of a treatment effect for IgM anti-MAG neuropathy and diabetic amyotrophy (radiculoplexus neuropathy) is lacking. Recognition of rare localizations of peripheral neuropathy is essential given the implications for diagnostic testing and treatment. Electrodiagnostic studies are an important Krukowski, Karen; Ma, Jiacheng; Golonzhka, Olga; Laumet, Geoffroy O; Gutti, Tanuja; van Duzer, John H; Mazitschek, Ralph; Jarpe, Matthew B; Heijnen, Cobi J; Kavelaars, Annemieke Chemotherapy-induced peripheral neuropathy is one of the most common doselimiting side-effects of cancer treatment. Currently, there is no FDA-approved treatment available. Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase whose function includes regulation of á-tubulin-dependent intracellular mitochondrial transport. Here we examined the effect of HDAC6 inhibition on established cisplatin-induced peripheral neuropathy. We used a novel HDAC6 inhibitor ACY-1083, which shows 260-fold selectivity towards HDAC6 versus other HDACs. Our results show that HDAC6 inhibition prevented cisplatin-induced mechanical allodynia, and also completely reversed already existing cisplatin-induced mechanical allodynia, spontaneous pain, and numbness. These findings were confirmed using the established HDAC6 inhibitor ACY-1215 (Ricolinostat), which is currently in clinical trials for cancer treatment. Mechanistically, treatment with the HDAC6 inhibitor increased á-tubulin acetylation in the peripheral nerve. In addition, HDAC6 inhibition restored the cisplatin-induced reduction in mitochondrial bioenergetics and mitochondrial content in the tibial nerve, indicating increased mitochondrial transport. At a later time point, dorsal root ganglion mitochondrial bioenergetics also improved. HDAC6 inhibition restored the loss of intra-epidermal nerve fiber density in cisplatin-treated mice. Our results demonstrate that pharmacological inhibition of HDAC6 completely reverses all the hallmarks of established cisplatin-induced peripheral neuropathy by normalization of mitochondrial function in DRG and nerve, and restoration of intra-epidermal innervation. These results are especially promising because one of the HDAC6 inhibitors tested here is currently in clinical trials as an add-on cancer therapy, highlighting the potential for a fast clinical translation of our findings. Nagashima, Satoshi; Kiba, Takayoshi; Ogawa, Yoshikazu; Mura, Takuya; Kajiume, Sayoko; Okada, Yuuko; Morii, Nao; Takahashi, Hirotoshi; Ichiba, Yasunori; Yamashiro, Hiroyasu Here, we report about a 60-year-old woman with metastatic breast cancer who was successfully treated for paclitaxelinduced peripheral neuropathy with duloxetine. She was administered trastuzumab plus paclitaxel(PTX)combination therapy that was ultimately discontinued because of grade 3 peripheral neuropathy detected on day 15, according to the CTCAE (v4.0). She was administered duloxetine on day 90 after the end of the previous therapy because of the peripheral neuropathy. Thereafter, the peripheral neuropathy decreased to grade 1, which enabled PTX administration on her request. Further trials are required to confirm the efficacy of duloxetine. Herrmann, David N Peripheral neuropathies are diverse and require a multidimensional approach for detection and monitoring in a clinical and research setting. This review describes non- and minimally-invasive measures of distal predominantly sensory polyneuropathy (DSP), the most common form of neuropathy. A combination of clinical and electrophysiologic assessment with nerve-conduction studies (NCSs) suffices for the detection and characterization of most DSPs. NCS are insensitive to variants of DSP that predominantly affect small diameter sensory nerve fibers (SFNs) and cutaneous nerve terminals that subserve pain and thermal sensation. Skin biopsy with assessment of epidermal nerve fiber density permits objective detection and monitoring of SFNs. Conventional clinical and NCS measures have limitations as outcomes in experimental therapeutics in DSP. For clinical trials, biopsy evaluation of epidermal innervation and emerging noninvasive imaging approaches (in vivo confocal microscopy of corneal innervation and of Meissner corpuscles in the skin) hold promise as surrogate markers that are complementary to traditional DSP measures. Kim, Young Ae; Kim, Eun Su; Hwang, Ho Kyeong; Lee, Kyung Bok; Lee, Sol; Jung, Ji Woong; Kwon, Yu Jin; Cho, Dong Hui; Park, Sang Su; Yoon, Jin; Jang, Yong-Seog Purpose: Peripheral neuropathy (PN) is known as a major contributor of the worsening of ischemic symptoms and the foot ulceration in patients with peripheral arterial occlusive disease (PAOD). However, there are few studies reporting the prevalence and risk factors for PN in PAOD. This study aimed to evaluate these issues for PN and to establish the importance of screening as additional treatment target for PN in PAOD. Materials and Methods: A total of 52 limbs with PAOD were enrolled from January 2011 to December 2012. PN was divided into radiculopathy, ischemic PN (IPN), and diabetic PN (DPN), based on electromyographic findings. We investigated the prevalence of overall PN and subtypes of PN and then analyzed the risk factors. Results: The prevalence of overall PN in PAOD was 43 of 52 limbs (82.7%). In terms of subtypes of PN, the prevalence rate of radiculopathy and IPN was 30.8% and 23.1%, respectively. DPN showed in 22 limbs (73.3%) among 30 diabetic limbs. There was no significant correlation between each type of PN and ischemic symptoms. Our analysis showed that coronary artery disease (CAD) was a significant risk factor (P=0.01) for IPN, however, did not identify any significant risk factors for DPN. Conclusion: This present study indicated that most patients with PAOD had PN and CAD was a risk factor for IPN. In particular, PAOD with diabetes represented a higher prevalence for DPN. Our study suggests that PN should be evaluated and considered as another treatment target in patients with PAOD. PMID:26217631 Mellion, Michelle L.; Silbermann, Elizabeth; Gilchrist, James M.; Machan, Jason T.; Leggio, Lorenzo; de la Monte, Suzanne Background Alcohol-related peripheral neuropathy (ALN) is generally characterized as an axonal large-fiber polyneuropathy caused by thiamine deficiency. We hypothesized, based on clinical observations, that ALN is associated with a small-fiber polyneuropathy that can be diagnosed with skin biopsy in heavy alcohol drinking subjects with normal thiamine status. Methods Eighteen individuals (9 heavy alcohol drinking subjects and 9 healthy control subjects) were assessed for the potential utility of skin biopsies in detecting ALN-associated small nerve fiber degeneration. Heavy drinking was defined as greater than 4 drinks/d and 5 drinks/d in women and men, respectively, as determined by the Timeline Follow-Back and lifetime drinking history. All subjects underwent neurological examination, nerve conduction studies, and skin biopsies to quantify end nerve fiber densities (ENFD). Other causes of neuropathy were excluded and thiamine status was assessed. Results Average ENFD were significantly decreased at the calf in the alcohol group as compared with control group (p < 0.0001). Histological sections demonstrated striking attrition and architectural simplification of intraepidermal nerve fibers in the heavy alcohol drinking subjects. There were no significant intergroup differences with respect to clinical assessments of neuropathy or thiamine status. Conclusions ALN is associated with a small-fiber neuropathy that can be detected with skin biopsy in heavy alcohol drinking individuals with normal thiamine status. Skin biopsy is a useful, minimally invasive biomarker that could extend studies to understand the effect of alcohol on the peripheral nerves and to evaluate potential therapeutic agents in larger clinical trials. PMID:24961481 Chiles, Nancy S; Phillips, Caroline L; Volpato, Stefano; Bandinelli, Stefania; Ferrucci, Luigi; Guralnik, Jack M; Patel, Kushang V Diabetes among older adults causes many complications, including decreased lower-extremity function and physical disability. Diabetes can cause peripheral nerve dysfunction, which might be one pathway through which diabetes leads to decreased physical function. The study aims were to determine the following: (1) whether diabetes and impaired fasting glucose are associated with objective measures of physical function in older adults, (2) which peripheral nerve function (PNF) tests are associated with diabetes, and (3) whether PNF mediates the diabetes-physical function relationship. This study included 983 participants, age 65 years and older from the InCHIANTI study. Diabetes was diagnosed by clinical guidelines. Physical performance was assessed using the Short Physical Performance Battery (SPPB), scored from 0 to 12 (higher values, better physical function) and usual walking speed (m/s). PNF was assessed via standard surface electroneurographic study of right peroneal nerve conduction velocity, vibration and touch sensitivity. Clinical cutpoints of PNF tests were used to create a neuropathy score from 0 to 5 (higher values, greater neuropathy). Multiple linear regression models were used to test associations. One hundred twenty-six (12.8%) participants had diabetes. Adjusting for age, sex, education, and other confounders, diabetic participants had decreased SPPB (β=-0.99; p<0.01), decreased walking speed (β=-0.1m/s; p<0.01), decreased nerve conduction velocity (β=-1.7m/s; p<0.01), and increased neuropathy (β=0.25; p<0.01) compared to non-diabetic participants. Adjusting for nerve conduction velocity and neuropathy score decreased the effect of diabetes on SPPB by 20%, suggesting partial mediation through decreased PNF. © 2014. Kim, Sok Ho; Kwon, Jung Kee; Kwon, Young Bae Pain symptoms are a common complication of diabetic peripheral neuropathy or an inflammatory condition. In the most experiments, only one or two evident pain modalities are observed at diabetic peripheral neuropathy according to experimental conditions. Following diabetic peripheral neuropathy or inflammation, spinal glial activation may be considered as an important mediator in the development of pain. For this reason, the present study was aimed to address the induction of pain modalities and spinal glial expression after streptozotocin injection as compared with that of zymosan inflammation in the rat. Evaluation of pain behavior by either thermal or mechanical stimuli was performed at 3 weeks or 5 hours after either intravenous streptozotocin or zymosan. Degrees of pain were divided into 4 groups: severe, moderate, mild, and non-pain induction. On the mechanical allodynia test, zymosan evoked predominantly a severe type of pain, whereas streptozotocin induced a weak degree of pain (severe+moderate: 57.1%). Although zymosan did not evoke cold allodynia, streptozotocin evoked stronger pain behavior, compared with zymosan (severe+moderate: 50.0%). On the other hand, the high incidence of thermal hyperalgesia (severe+moderate: 90.0%) and mechanical hyperalgesia (severe+moderate: 85.7%) by streptozotocin was observed, as similar to that of zymosan. In the spinal cord, the increase of microglia and astrocyte was evident by streptozotocin, only microglia was activated by zymosan. Therefore, it is recommended that the selection of mechanical and thermal hyperalgesia is suitable for the evaluation of streptozotocin induced diabetic peripheral neuropathy. Moreover, spinal glial activation may be considered an important factor. Shin, Susan C.; Robinson-Papp, Jessica Peripheral neuropathy is a common complication of many of the systemic amyloidoses. Although the cause of neuropathy is not entirely clear, it is likely related to amyloid deposition within the nerve. This may lead to focal, multifocal, or diffuse neuropathies involving sensory, motor and/or autonomic fibers. The presenting symptoms depend on the distribution of nerves affected. One of the most common phenotypes is sensorimotor polyneuropathy, which is characterized by symptoms of neuropathic pain, numbness, and in advanced cases weakness. Symptoms begin in the feet and ultimately progress to the proximal legs and hands. The most common focal neuropathy is a median neuropathy at the wrist, or clinically known as carpal tunnel syndrome. Carpal tunnel symptoms may include pain and sensory disturbances in the lateral palm and fingers; hand weakness may ensue if the focal neuropathy is severe. Autonomic neuropathy may affect a variety of organ systems such as the cardiovascular, gastrointestinal, and genitourinary systems. Symptoms may be non-specific making the diagnosis of autonomic neuropathy more difficult to identify. However, it is important to recognize and distinguish autonomic neuropathy from diseases of the end-organs themselves. This chapter reviews the inherited and acquired amyloidoses that affect the peripheral nervous system including familial amyloid polyneuropathy, and primary, secondary and senile amyloidosis. We emphasize the clinical presentation of the neurologic aspects of these diseases, physical examination findings, appropriate diagnostic evaluation, treatment and prognosis. PMID:23239211 Shin, Susan C; Robinson-Papp, Jessica Peripheral neuropathy is a common complication of many of the systemic amyloidoses. Although the cause of neuropathy is not entirely clear, it is likely related to amyloid deposition within the nerve. This may lead to focal, multifocal, or diffuse neuropathies involving sensory, motor and/or autonomic fibers. The presenting symptoms depend on the distribution of nerves affected. One of the most common phenotypes is sensorimotor polyneuropathy, which is characterized by symptoms of neuropathic pain, numbness, and in advanced cases weakness. Symptoms begin in the feet and ultimately progress to the proximal legs and hands. The most common focal neuropathy is a median neuropathy at the wrist, clinically known as carpal tunnel syndrome. Carpal tunnel symptoms may include pain and sensory disturbances in the lateral palm and fingers; hand weakness may ensue if the focal neuropathy is severe. Autonomic neuropathy may affect a variety of organ systems such as the cardiovascular, gastrointestinal, and genitourinary systems. Symptoms may be non-specific making the diagnosis of autonomic neuropathy more difficult to identify. However, it is important to recognize and distinguish autonomic neuropathy from diseases of the end-organs themselves. This article reviews the inherited and acquired amyloidoses that affect the peripheral nervous system including familial amyloid polyneuropathy, and primary, secondary and senile amyloidosis. We emphasize the clinical presentation of the neurologic aspects of these diseases, physical examination findings, appropriate diagnostic evaluation, treatment and prognosis. © 2012 Mount Sinai School of Medicine. Toumi, S; Hammouda, M; Essid, A; Medimagh, L; Slamia, L Ben; Laouani-Kechrid, C Metronidazole is a widely prescribed treatment for amoebic and anaerobic germ infections. Its neurologic toxicity is rare but can be serious. We report the case of a 27-year-old male patient, treated with metronidazole for a cerebral abscess. He presented with a cerebellar syndrome and peripheral neuropathy at a cumulative metronidazole dose of 60g. The MRI aspect of the cerebellar lesions in addition to their reversibility after treatment cessation led to the diagnosis of metronidazole induced neurologic toxicity. The occurrence of neurologic disorders in patients treated with metronidazole must suggest drug toxicity and lead to cessation of treatment. Benstead, Tim J; Chalk, Colin H; Parks, Natalie E disability scale), electrodiagnostic measures, number of participants with improved symptoms of neuropathy (global impression of change), and severe adverse events. Four trials of HCV-related cryoglobulinemia fulfiled selection criteria and the review authors included three in quantitative synthesis. All studies were at high risk of bias. No trial addressed the primary outcome of change in sensory impairment. No trial addressed secondary outcomes of change in combined sensory and motor impairment, disability, or electrodiagnostic measures. A single trial of HCV-related mixed cryoglobulinemia treated with pegylated interferon alfa (peginterferon alfa), ribavirin, and rituximab versus peginterferon alfa and ribavirin did not show a significant difference in the number of participants with improvement in neuropathy at 36 months post treatment (risk ratio (RR) 4.00, 95% confidence interval (CI) 0.27 to 59.31, n = 9). One study of interferon alfa (n = 22) and two studies of rituximab (n = 61) provided adverse event data. Severe adverse events were no more common with interferon alfa (RR 7.00, 95% CI 0.38 to 128.02) or rituximab (RR 3.00, 95% CI 0.13 to 67.06) compared to the control group. There is a lack of RCTs and quasi-RCTs addressing the effects of interventions for peripheral neuropathy associated with HCV infection. At present, there is insufficient evidence from RCTs and quasi-RCTs to make evidence-based decisions about treatment. Kuo, Hung-Chou; Chu, Chun-Che; Jung, Shih-Ming; Huang, Chin-Chang We report an unusual clinical course of peripheral neuropathy in a patient with neurofibromatosis type 2 (NF2). Clinically, a progressive course of focal amyotrophy had been noted since childhood, followed by bilateral vestibular and intraspinal schwannomas at the fourth decade, and then chronic asymmetric polyneuropathy after menopause. Electrophysiological studies revealed a predominantly axonal type of peripheral neuropathy. A sural nerve biopsy showed an abundant proliferation of Schwann cells and a reduction of the large myelinated fibers. A review of the literature showed that peripheral neuropathy might present with focal amyotrophy, mononeuropathy, mononeuropathy multiplex, or symmetric or asymmetric polyneuropathy in patients with NF2. The etiologies of peripheral neuropathy in patients with NF2 include an abnormal proliferation of Schwann cells and tumorlet compression of the peripheral nerves. From our study, we conclude that an abundant proliferation of Schwann cells plays an important role in the pathogenesis of peripheral neuropathy in patients with NF2. Truman, Richard W; Ebenezer, Gigi J; Pena, Maria T; Sharma, Rahul; Balamayooran, Gayathriy; Gillingwater, Thomas H; Scollard, David M; McArthur, Justin C; Rambukkana, Anura Leprosy (also known as Hansen's Disease) is a chronic infectious disease caused by Mycobacterium leprae that primarily targets the peripheral nervous system; skin, muscle, and other tissues are also affected. Other than humans, nine-banded armadillos (Dasypus novemcinctus) are the only natural hosts of M. leprae, and they are the only laboratory animals that develop extensive neurological involvement with this bacterium. Infection in the armadillo closely recapitulates many of the structural, physiological, and functional aspects of leprosy seen in humans. Armadillos can be useful models of leprosy for basic scientific investigations into the pathogenesis of leprosy neuropathy and its associated myopathies, as well as for translational research studies in piloting new diagnostic methods or therapeutic interventions. Practical and ethical constraints often limit investigation into human neuropathies, but armadillos are an abundant source of leprotic neurologic fibers. Studies with these animals may provide new insights into the mechanisms involved in leprosy that also might benefit the understanding of other demyelinating neuropathies. Although there is only a limited supply of armadillo-specific reagents, the armadillo whole genomic sequence has been completed, and gene expression studies can be employed. Clinical procedures, such as electrophysiological nerve conduction testing, provide a functional assessment of armadillo nerves. A variety of standard histopathological and immunopathological procedures including Epidermal Nerve Fiber Density (ENFD) analysis, Schwann Cell Density, and analysis for other conserved cellular markers can be used effectively with armadillos and will be briefly reviewed in this text. Truman, Richard W.; Ebenezer, Gigi J.; Pena, Maria T.; Sharma, Rahul; Balamayooran, Gayathriy; Gillingwater, Thomas H.; Scollard, David M.; McArthur, Justin C.; Rambukkana, Anura Leprosy (also known as Hansen's Disease) is a chronic infectious disease caused by Mycobacterium leprae that primarily targets the peripheral nervous system; skin, muscle, and other tissues are also affected. Other than humans, nine-banded armadillos (Dasypus novemcinctus) are the only natural hosts of M. leprae, and they are the only laboratory animals that develop extensive neurological involvement with this bacterium. Infection in the armadillo closely recapitulates many of the structural, physiological, and functional aspects of leprosy seen in humans. Armadillos can be useful models of leprosy for basic scientific investigations into the pathogenesis of leprosy neuropathy and its associated myopathies, as well as for translational research studies in piloting new diagnostic methods or therapeutic interventions. Practical and ethical constraints often limit investigation into human neuropathies, but armadillos are an abundant source of leprotic neurologic fibers. Studies with these animals may provide new insights into the mechanisms involved in leprosy that also might benefit the understanding of other demyelinating neuropathies. Although there is only a limited supply of armadillo-specific reagents, the armadillo whole genomic sequence has been completed, and gene expression studies can be employed. Clinical procedures, such as electrophysiological nerve conduction testing, provide a functional assessment of armadillo nerves. A variety of standard histopathological and immunopathological procedures including Epidermal Nerve Fiber Density (ENFD) analysis, Schwann Cell Density, and analysis for other conserved cellular markers can be used effectively with armadillos and will be briefly reviewed in this text. PMID:24615444 Kavcic, Marko; Koritnik, Blaz; Krzan, Matevz; Velikonja, Orjana; Prelog, Tomaz; Stefanovic, Milica; Debeljak, Maruša; Jazbec, Janez Patients treated with vincristine predictably develop peripheral neuropathy. The aim of our study was to investigate the pattern of vincristine-induced neuropathy in children by nerve conduction studies and somatosensory-evoked potentials (SSEPs). We included data from 39 children who received vincristine for various pediatric malignancies, and we performed initial and follow-up (after a minimum of 4 doses of vincristine 1.5 mg/m) conduction studies in 27 patients and SSEPs studies in 34 patients. On follow-up the most prevalent symptoms were paresthesias (44%) and constipation (22%), and the most common neurological sign was impaired myotatic reflexes (89%). Performing nerve conduction studies we found that significant reductions were measured for distal amplitudes, distal latencies were prolonged, and conduction velocities were relatively preserved. The most pronounced differences in amplitudes and distal latencies were measured in the peroneal nerves. Changes of SSEPs studies were subtle. Vincristine-induced neuropathy presents with primary axonal involvement and is more pronounced on motor neurons. We found a trend between higher age and higher dose and the degree of neuropathy in our group of patients. Coriat, Romain; Alexandre, Jérôme; Nicco, Carole; Quinquis, Laurent; Benoit, Evelyne; Chéreau, Christiane; Lemaréchal, Hervé; Mir, Olivier; Borderie, Didier; Tréluyer, Jean-Marc; Weill, Bernard; Coste, Joel; Goldwasser, François; Batteux, Frédéric Background. The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity involves ROS production, we investigated the efficacy of mangafodipir, a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer. Methods. The effects of mangafodipir were examined in mice following treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23 cancer patients with grade ≥2 oxaliplatin-induced neuropathy in a phase II study, with 22 patients receiving i.v. mangafodipir following oxaliplatin. Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir. Results. Mangafodipir prevented motor and sensory dysfunction and demyelinating lesion formation. In mice, serum AOPPs decreased after 4 weeks of mangafodipir treatment. In 77% of patients treated with oxaliplatin and mangafodipir, neuropathy improved or stabilized after 4 cycles. After 8 cycles, neurotoxicity was downgraded to grade ≥2 in 6 of 7 patients. Prior to enrollment, patients received an average of 880 ± 239 mg/m2 oxaliplatin. Patients treated with mangafodipir tolerated an additional dose of 458 ± 207 mg/m2 oxaliplatin despite preexisting neuropathy. Mangafodipir responders managed a cumulative dose of 1,426 ± 204 mg/m2 oxaliplatin. Serum AOPPs were lower in responders compared with those in nonresponders. Conclusion. Our study suggests that mangafodipir can prevent and/or relieve oxaliplatin-induced neuropathy in cancer patients. Trial registration. Clinicaltrials.gov NCT00727922. Funding. Université Paris Descartes, Ministère de la Recherche et de l’Enseignement Supérieur, and Assistance Publique-Hôpitaux de Paris. PMID:24355920 Premkumar, Louis S; Pabbidi, Reddy M The prevalence of diabetes has reached epidemic proportions. There are two forms of diabetes: type 1 diabetes mellitus is due to auto-immune-mediated destruction of pancreatic β-cells resulting in absolute insulin deficiency and type 2 diabetes mellitus is due to reduced insulin secretion and or insulin resistance. Both forms of diabetes are characterized by chronic hyperglycemia, leading to the development of diabetic peripheral neuropathy (DPN) and microvascular pathology. DPN is characterized by enhanced or reduced thermal, chemical, and mechanical pain sensitivities. In the long-term, DPN results in peripheral nerve damage and accounts for a substantial number of non-traumatic lower-limb amputations. This review will address the mechanisms, especially the role of reactive oxygen and nitrogen species in the development and progression of DPN. Kim, Peggy Y; Johnson, Carrie E Chemotherapy-induced peripheral neuropathy (CIPN) is a common, frequently chronic condition characterized by pain and decreased function. Given the growing number of cancer survivors and an increasing recognition of opioid therapy limitations, there is a need for critical analysis of the literature in directing an informed and thoughtful approach for the management of painful CIPN. A PubMed search for 'chemotherapy-induced peripheral neuropathy AND pain' identifies 259 publications between 1 January 2016 and 31 March 2017. Based on review of this literature, we aim to present a clinically relevant update of painful CIPN. Notably, the use of duloxetine as a first-line agent in treatment of CIPN is confirmed. Moreover, clinical trials focus on nonpharmacologic strategies for managing painful CIPN. Despite the volume of recent publications, there are limited preventive or therapeutic strategies for CIPN supported by high-level evidence. Duloxetine remains the only pharmacologic agent with demonstrated benefit; its clinical use should be routinely considered. Moving forward, nonopioid analgesic therapies will likely play an increasing role in CIPN treatment, but further research is necessary to confirm their utility. Promising therapies include vitamin B12 supplementation, physical therapy, and various forms of neuromodulation. Mensa, Mussa; Cubitt, Jonathan James; Javed, Muhammad; Bragg, Thomas All animal bites have the potential to cause significant infection. In the UK, dogs are the most common source of bites. Incidence of hospital attendances attributable to dog bites has risen over the last decade. Patient groups at particular risk of bites and/or complications of infection include those at extremes of age, immunosuppressed and patients with diabetes. We report the case of a patient with diabetic peripheral neuropathy, who was admitted on two separate occasions with unprovoked bites to his toes whilst asleep, by his pet dog. He ultimately required terminalisation of the affected digits. Although unusual, this mechanism of injury has been previously described in literature. However, we are unaware of cases reporting multiple separate incidences involving the same patient and animal. We present this case to highlight the perils of untrained pet ownership in diabetic patients with peripheral neuropathy and the importance of prompt medical and surgical treatment of injuries. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Haidar, Mansour; Timmerman, Vincent The inherited peripheral neuropathies (IPNs) comprise a growing list of genetically heterogeneous diseases. With mutations in more than 80 genes being reported to cause IPNs, a wide spectrum of functional consequences is expected to follow this genotypic diversity. Hence, the search for a common pathomechanism among the different phenotypes has become the holy grail of functional research into IPNs. During the last decade, studies on several affected genes have shown a direct and/or indirect correlation with autophagy. Autophagy, a cellular homeostatic process, is required for the removal of cell aggregates, long-lived proteins and dead organelles from the cell in double-membraned vesicles destined for the lysosomes. As an evolutionarily highly conserved process, autophagy is essential for the survival and proper functioning of the cell. Recently, neuronal cells have been shown to be particularly vulnerable to disruption of the autophagic pathway. Furthermore, autophagy has been shown to be affected in various common neurodegenerative diseases of both the central and the peripheral nervous system including Alzheimer’s, Parkinson’s, and Huntington’s diseases. In this review we provide an overview of the genes involved in hereditary neuropathies which are linked to autophagy and we propose the disruption of the autophagic flux as an emerging common pathomechanism. We also shed light on the different steps of the autophagy pathway linked to these genes. Finally, we review the concept of autophagy being a therapeutic target in IPNs, and the possibilities and challenges of this pathway-specific targeting. PMID:28553203 Haidar, Mansour; Timmerman, Vincent The inherited peripheral neuropathies (IPNs) comprise a growing list of genetically heterogeneous diseases. With mutations in more than 80 genes being reported to cause IPNs, a wide spectrum of functional consequences is expected to follow this genotypic diversity. Hence, the search for a common pathomechanism among the different phenotypes has become the holy grail of functional research into IPNs. During the last decade, studies on several affected genes have shown a direct and/or indirect correlation with autophagy. Autophagy, a cellular homeostatic process, is required for the removal of cell aggregates, long-lived proteins and dead organelles from the cell in double-membraned vesicles destined for the lysosomes. As an evolutionarily highly conserved process, autophagy is essential for the survival and proper functioning of the cell. Recently, neuronal cells have been shown to be particularly vulnerable to disruption of the autophagic pathway. Furthermore, autophagy has been shown to be affected in various common neurodegenerative diseases of both the central and the peripheral nervous system including Alzheimer's, Parkinson's, and Huntington's diseases. In this review we provide an overview of the genes involved in hereditary neuropathies which are linked to autophagy and we propose the disruption of the autophagic flux as an emerging common pathomechanism. We also shed light on the different steps of the autophagy pathway linked to these genes. Finally, we review the concept of autophagy being a therapeutic target in IPNs, and the possibilities and challenges of this pathway-specific targeting. Mold, James W; Vesely, Sara K; Keyl, Barbara A; Schenk, Joan B; Roberts, Michelle The prevalence, predictors, and consequences of peripheral neuropathy in the elderly have not been well defined. Seven hundred ninety-five noninstitutionalized patients 65 years of age and older, recruited from the practices of family physicians, completed questionnaires and underwent peripheral neurologic examinations and tests of gait and balance. Variables included sociodemographic information, medical conditions, symptoms (numbness, pain, trouble with balance or walking, and restless legs), quality of life measures, ankle reflexes, position sense, vibratory sense, fine touch sensation, Tinnetti balance examination, and a 50-foot timed walk. The prevalence of at least one bilateral sensory deficit rose from 26% for 65- to 74-year-olds to 54% for those 85 and older. The most common deficit was loss of ankle reflex followed by loss of fine touch. Only 40% of those with bilateral deficits reported having a disease known to cause peripheral neuropathy. Predictors of bilateral deficits included increasing age, income less than 15,000 dollars, a history of military service, increasing body mass index, self-reported history of diabetes mellitus, Vitamin B12 deficiency or rheumatoid arthritis, and absence of a history of hypertension. Deficits were associated with numbness, pain, restless legs, trouble walking, trouble with balance, and reduced quality of life. Peripheral sensory deficits are common in the elderly. In most cases, a medical cause is not obvious. Their consequences may not be as benign as often supposed. Carvalho, Larissa F; Silva, Ana Maria F; Carvalho, Adriana A Antineoplastic drugs such as cisplatin, oxaliplatin, paclitaxel and vincristin are widely used in the treatment of several solid and blood tumours. However, the severity of peripheral neuropathy caused by these agents can affect the patient's quality of life. The major symptoms of chemotherapy-induced peripheral neuropathy (CIPN) involve: sensory loss, paresthesia, dysesthaesia, numbness, tingling, temperature sensitivity, allodynia and hyperalgesia, in a "stocking and glove" distribution. Why many different chemotherapeutic agents result in similar neuropathy profiles is unclear. Many drug classes such as antidepressants, anticonvulsants, antispastic agents and others have been used in clinical practice, but there is no scientific evidence to prove their effectiveness. But drugs as the antioxidant have shown a protective effect against free radical damage. In order to find out a successful treatment for CIPN, animal studies (ie pharmacological and mechanical tests and histopathological immunohistochemical analyses) have been developed to try to determinate the action of the antioxidant agents. This review provides an overview of the major antioxidant agents recently investigated to treat CIPN and the animal models used for this purpose. © 2017 John Wiley & Sons Australia, Ltd. Yamamoto, Shota; Kawashiri, Takehiro; Higuchi, Hitomi; Tsutsumi, Kuniaki; Ushio, Soichiro; Kaname, Takanori; Shirahama, Masafumi; Egashira, Nobuaki Bortezomib, an effective anticancer drug for multiple myeloma, often causes peripheral neuropathy which is mainly characterized by numbness and painful paresthesia. Nevertheless, there is no effective strategy to escape or treat bortezomib-induced peripheral neuropathy (BIPN), because we have understood few mechanism of this side effect. In this study, we evaluated behavioral and pathological characteristics of BIPN, and investigated pharmacological efficacy of various analgesic drugs and adjuvants on mechanical allodynia induced by bortezomib treatment in rats. The repeated administration of bortezomib induced mechanical and cold allodynia. There was axonal degeneration of sciatic nerve behind these neuropathic symptoms. Furthermore, the exposure to bortezomib shortened neurite length in PC12 cells. Finally, the result of evaluation of anti-allodynic potency, oral administration of tramadol (10 mg/kg), pregabalin (3 mg/kg), duloxetine (30 mg/kg) or mexiletine (100 mg/kg), but not amitriptyline or diclofenac, transiently relieved the mechanical allodynia induced by bortezomib. These results suggest that axonal degeneration of the sciatic nerve is involved in BIPN and that some analgesic drugs and adjuvants are effective in the relief of painful neuropathy. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved. Diabetes mellitus is the commonest cause of an autonomic neuropathy in the developed world. Diabetic autonomic neuropathy causes a constellation of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. Several discrete syndromes associated with diabetes cause autonomic dysfunction. The most prevalent of these are: generalized diabetic autonomic neuropathy, autonomic neuropathy associated with the prediabetic state, treatment-induced painful and autonomic neuropathy, and transient hypoglycemia-associated autonomic neuropathy. These autonomic manifestations of diabetes are responsible for the most troublesome and disabling features of diabetic peripheral neuropathy and result in a significant proportion of the mortality and morbidity associated with the disease. Turkiew, Elliot; Falconer, Debbie; Reed, Nicole; Höke, Ahmet Distal axon degeneration seen in many peripheral neuropathies is likely to share common molecular mechanisms with Wallerian degeneration. Although several studies in mouse models of peripheral neuropathy showed prevention of axon degeneration in the slow Wallerian degeneration (Wlds) mouse, the role of a recently identified player in Wallerian degeneration, Sarm1, has not been explored extensively. In this study, we show that mice lacking the Sarm1 gene are resistant to distal axonal degeneration in a model of chemotherapy induced peripheral neuropathy caused by paclitaxel and a model of high fat diet induced putative metabolic neuropathy. This study extends the role of Sarm1 to axon degeneration seen in peripheral neuropathies and identifies it as a likely target for therapeutic development. © 2017 Peripheral Nerve Society. Zhang, Jing-bo; Zhang, Qiao-yun; Wang, Yong; Sun, Dao-yuan To study the nerve electromyogram results by analysing the pathological characters of 4 cases diagnosed as peripheral neuropathy caused by n-hexane and arsenic. The nerve electromyogram examination and pathology data of 4 patients, who had been diagnosed as toxic chemicals peripheral neuropathy, were studied retrospectively. Two patients in this group were exposed to n-hexane, their nerve electromyogram examinations and biopsy pathology of superficial peroneal nerve indicated the peripheral neuropathy was mainly manifests the lesion of medullary sheath. Another two patients were exposed to arsenic, their nerve electromyogram examinations showed axonal degeneration associated with demyelination, and their biopsy pathology showed the peripheral neuropathy was mainly axonal degeneration. Axonal degeneration and demyelination always coexist in peripheral neuropathy caused by chemicals. Griffith, Kathleen A; Zhu, Shijun; Johantgen, Meg; Kessler, Michael D; Renn, Cynthia; Beutler, Andreas S; Kanwar, Rahul; Ambulos, Nicholas; Cavaletti, Guido; Bruna, Jordi; Briani, Chiara; Argyriou, Andreas A; Kalofonos, Haralabos P; Yerges-Armstrong, Laura M; Dorsey, Susan G Oxaliplatin-induced peripheral neuropathy (OIPN) is a dose limiting toxicity of oxaliplatin and affects most colorectal cancer (CRC) patients. OIPN is commonly evaluated by patient symptom report, using scales to reflect impairment. They do not discriminate between unique grouping of symptoms and signs, which impedes prompt identification of OIPN. Our study objective was to identify clusters of symptoms and signs that differentiated underlying clinical severity and segregated patients within our population into OIPN subgroups. Chemotherapy naïve CRC patients (N=148) receiving oxaliplatin were administered the Total Neuropathy Score clinical (TNSc(©)), which includes symptom report (sensory, motor, autonomic) and sensory examination (pin sense, vibration, reflexes). The TNSc(©) was administered prior to chemotherapy initiation (T0), and following cumulative doses of oxaliplatin 510-520 mg/m(2) (T1) and 1020-1040 mg/ m(2) of oxaliplain (T2). Using mean T2 TNSc(©) scores, latent class analysis (LCA) grouped patients into OIPN severity cohorts. LCA categorized patients into 4 distinct OIPN groups: low symptoms and low signs (N=54); low symptoms and intermediate signs (n=44); low symptoms and high signs (n=21); and high symptoms and high signs (n=29). No differences were noted among OIPN groups on age, sex, chemotherapy regimen, or cumulative oxaliplatin dose. We identified OIPN patient groups with distinct symptoms/signs, demonstrating variability of OIPN presentation regardless of cumulative oxaliplatin dose. Over half of the sample had positive findings on OIPN examination despite little or no symptoms. Sensory examination of all patients receiving oxaliplatin is indicated for timely identification of OIPN, which will allow earlier symptom management. Copyright © 2017. Published by Elsevier Inc. Yardimci, Nilgul; Cemeroglu, Ozlem; Ozturk, Eda; Gürlü, Gülsüm; Şahin, Esra; Bozkurt, Saliha; Cengiz, Tugba; Karali, Gulderen; Cakirbay, Hasim; İlhan, Atilla Background. While increasing evidence suggests comorbidity of peripheral neuropathy (PNP) and Parkinson's disease (PD), the pathogenesis of PNP in PD is still a debate. The aim of this article is to search the core PD symptoms such as rigidity and tremor as contributing factors to mononeuropathy development while emphasizing each individual patient's asymmetric symptom severity. Methods. We studied 62 wrists and 62 elbows of 31 patients (mean age 66.48 ± 10.67) and 64 wrists and 64 elbows of 32 age-gender matched healthy controls (mean age 62.03 ± 10.40, p = 0.145). The Hoehn and Yahr disability scale and Unified Parkinson's Disease Rated Scale were used to determine the severity of the disease. Results. According to electrodiagnostic criteria, we confirmed median neuropathy in 16.12% (bilateral in two-thirds of the patients) and ulnar neuropathy in 3.22% of the PD group. While mean age (p = 0.003), age at PD onset (p = 0.019), and H&Y scores (p = 0.016) were significant, tremor and rigidity scores were not. The comparison of the mean indices of electrophysiologic parameters indicated subclinical median and ulnar nerve demyelination both at the wrist and at the elbow in the patient groups where a longer disease duration and mild tremor and rigidity scores are prominent, remarkably. Conclusion. A disease related peripheral neurodegeneration beyond symptom severity occurs in PD. Cemeroglu, Ozlem; Ozturk, Eda; Gürlü, Gülsüm; Şahin, Esra; Bozkurt, Saliha; Cengiz, Tugba; Karali, Gulderen; Cakirbay, Hasim; İlhan, Atilla Background. While increasing evidence suggests comorbidity of peripheral neuropathy (PNP) and Parkinson's disease (PD), the pathogenesis of PNP in PD is still a debate. The aim of this article is to search the core PD symptoms such as rigidity and tremor as contributing factors to mononeuropathy development while emphasizing each individual patient's asymmetric symptom severity. Methods. We studied 62 wrists and 62 elbows of 31 patients (mean age 66.48 ± 10.67) and 64 wrists and 64 elbows of 32 age-gender matched healthy controls (mean age 62.03 ± 10.40, p = 0.145). The Hoehn and Yahr disability scale and Unified Parkinson's Disease Rated Scale were used to determine the severity of the disease. Results. According to electrodiagnostic criteria, we confirmed median neuropathy in 16.12% (bilateral in two-thirds of the patients) and ulnar neuropathy in 3.22% of the PD group. While mean age (p = 0.003), age at PD onset (p = 0.019), and H&Y scores (p = 0.016) were significant, tremor and rigidity scores were not. The comparison of the mean indices of electrophysiologic parameters indicated subclinical median and ulnar nerve demyelination both at the wrist and at the elbow in the patient groups where a longer disease duration and mild tremor and rigidity scores are prominent, remarkably. Conclusion. A disease related peripheral neurodegeneration beyond symptom severity occurs in PD. PMID:27843673 Boulton, A J Diabetic peripheral neuropathy is estimated to affect at least 30% of patients with diabetes mellitus. The appropriate management of this disturbance is essential if late-stage complications, such as foot ulceration and amputations, are to be avoided in these patients. The need for improvements in the clinical management of neuropathy in primary and outpatient hospital care resulted in the identification of an international consensus group to address the management of diabetic peripheral neuropathy by the practising clinician. The international consensus group included diabetologists, neurologists, primary care clinicians, diabetes specialist nurses and podiatrists. The outcome of this consensus group was endorsed by the Neurodiab Executive Committee. The International Guidelines describe the recommendations for the management of diabetes in primary care and in outpatient hospital care and include an annual review of diabetic patients. This should include a history of patient symptoms, the type of diabetes, lifestyle and social circumstances. In examination of the foot, the status of the skin (e.g. absence of sweating and presence of ulceration) immobility of joints, gait and footwear should be noted. Simple tests should be performed to assess peripheral sensation, including sensation to pinprick, light touch, vibration, pressure, and ankle reflexes should be checked. It is the objective of the guidelines document to provide clear and simple instructions for the diagnosis and management of neuropathy on an outpatient basis, in particular during annual review of the patient. Adoption of the guidelines should lead to improvements in the management of neuropathy. Xue, Hong-xia; Fu, Wen-yi; Cui, Hua-dong; Yang, Li-li; Zhang, Ning; Zhao, Li-juan Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide. PMID:26109960 Xue, Hong-Xia; Fu, Wen-Yi; Cui, Hua-Dong; Yang, Li-Li; Zhang, Ning; Zhao, Li-Juan Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide. Dimitrova, Alexandra; Murchison, Charles; Oken, Barry .001) favoring acupuncture over control for neuropathic symptoms. Acupuncture is beneficial in some peripheral neuropathies, but more rigorously designed studies using sham-acupuncture control are needed to characterize its effect and optimal use better. Bilir, Bulent; Tulubas, Feti; Bilir, Betul Ekiz; Atile, Neslihan Soysal; Kara, Sonat Pinar; Yildirim, Tulay; Gumustas, Seyit Ali; Topcu, Birol; Kaymaz, Ozlem; Aydin, Murat [Purpose] The effects of vitamin D on the circulating levels of IL-17 and IL-13 were investigated in patients with diabetic peripheral neuropathy, patients with diabetes mellitus type 2 without neuropathy, and healthy controls. [Subjects and Methods] A single-blind controlled clinical study was performed, including70 type 2 diabetic patients with or without diabetic peripheral neuropathy and 33 healthy volunteer controls. The 25(OH)D levels were evaluated using ultra-performance liquid chromatography, and IL-17 and IL-13 levels were assessed using enzyme-linked immunosorbent assays. [Results] The 25(OH) vitamin D concentration was lower in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy and healthy controls. Similarly, 25(OH)D levels were lower in diabetes mellitus patients than healthy controls. IL-17 and IL-13 levels were higher in diabetes mellitus patients than in controls. Additionally, IL-13 levels were higher in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy. These differences were statistically significant. There was a significant positive correlation between 25(OH)D and IL-13,and a negative correlation between 25(OH)D andIL-17 in the diabetic and diabetic neuropathy groups. [Conclusion] Vitamin D is a potential modifiable risk factor for diabetic peripheral neuropathy and may regulate inflammatory mediators, e.g., IL-17 and IL-13. Bindu, Parayil Sankaran; Govindaraju, Chikanna; Sonam, Kothari; Nagappa, Madhu; Chiplunkar, Shwetha; Kumar, Rakesh; Gayathri, Narayanappa; Bharath, M M Srinivas; Arvinda, Hanumanthapura R; Sinha, Sanjib; Khan, Nahid Akthar; Govindaraj, Periyasamy; Nunia, Vandana; Paramasivam, Arumugam; Thangaraj, Kumarasamy; Taly, Arun B There are relatively few studies, which focus on peripheral neuropathy in large cohorts of genetically characterized patients with mitochondrial disorders. This study sought to analyze the pattern of peripheral neuropathy in a cohort of patients with mitochondrial disorders. The study subjects were derived from a cohort of 52 patients with a genetic diagnosis of mitochondrial disorders seen over a period of 8 years (2006-2013). All patients underwent nerve conduction studies and those patients with abnormalities suggestive of peripheral neuropathy were included in the study. Their phenotypic features, genotype, pattern of peripheral neuropathy and nerve conduction abnormalities were analyzed retrospectively. The study cohort included 18 patients (age range: 18 months-50 years, M:F- 1.2:1).The genotype included mitochondrial DNA point mutations (n=11), SURF1 mutations (n=4) and POLG1(n=3). Axonal neuropathy was noted in 12 patients (sensori-motor:n=4; sensory:n=4; motor:n=4) and demyelinating neuropathy in 6. Phenotype-genotype correlations revealed predominant axonal neuropathy in mtDNA point mutations and demyelinating neuropathy in SURF1. Patients with POLG related disorders had both sensory ataxic neuropathy and axonal neuropathy. A careful analysis of the family history, clinical presentation, biochemical, histochemical and structural analysis may help to bring out the mitochondrial etiology in patients with peripheral neuropathy and may facilitate targeted gene testing. Presence of demyelinating neuropathy in Leigh's syndrome may suggest underlying SURF1 mutations. Sensory ataxic neuropathy with other mitochondrial signatures should raise the possibility of POLG related disorder. Copyright © 2015. Published by Elsevier B.V. Siepmann, T; Penzlin, A I; Illigens, B M W Autonomic neuropathies are a heterogeneous group of diseases that involve damage of small peripheral autonomic Aδ- and C-fibers. Causes of autonomic nerve fiber damage are disorders such as diabetes mellitus and HIV-infection. Predominant symptoms of autonomic neuropathy are orthostatic hypotension, gastro-intestinal problems, urogenital dysfunction, and cardiac arrhythmia, which can severely impair the quality of life in affected patients. Furthermore, autonomic neuropathies can be induced by autoimmune diseases such as acute inflammatory demyelinating polyneuropathy, hereditary disorders such as the lysosomal storage disorder Fabry disease and hereditary sensory and autonomic neuropathies, as well as certain toxins and drugs. © Georg Thieme Verlag KG Stuttgart · New York. Similarly to entrapment neuropathies of upper extremities, the ultrasound constitutes a valuable supplementation of diagnostic examinations performed in patients with suspicions of nerve entrapment syndromes of the lower limb. For many years, it was claimed that such pathologies were rare. This probably resulted from the lack of proper diagnostic tools (including high frequency ultrasound transducers) as well as the lack of sufficient knowledge in this area. In relation to the above, the symptoms of compression neuropathies were frequently interpreted as a manifestation of pathologies of the lumbar part of the spine or a other orthopedic disease (degenerative or overuse one). Consequently, many patients were treated ineffectively for many months and even, years which led to irreparable neurological changes and changes in the motor organ. Apart from a clinical examination, the diagnostics of entrapment neuropathies of lower limb is currently based on imaging tests (ultrasound, magnetic resonance) as well as functional assessments (electromyography). Magnetic resonance imaging is characterized by a relatively low resolution (as compared to ultrasound) which results in limited possibilities of morphological evaluation of the visualized pathology. Electromyography allows for the assessment of nerve function, but does not precisely determine the type and degree of change. This article presents examples of the most common entrapment neuropathies of the lower limb concerning the following nerves: sciatic, femoral, lateral femoral cutaneous, obturator, fibular and its branches, tibial and its branches as well as sural. The pathomorphological basis of the neuropathies as well as corresponding ultrasound images are presented in this paper. Attention has been drawn to echogenicity, degree of vascularization and bundle presentation of the trunk of a pathological peripheral nerve. PMID:26673938 Kowalska, Berta; Sudoł-Szopińska, Iwona Similarly to entrapment neuropathies of upper extremities, the ultrasound constitutes a valuable supplementation of diagnostic examinations performed in patients with suspicions of nerve entrapment syndromes of the lower limb. For many years, it was claimed that such pathologies were rare. This probably resulted from the lack of proper diagnostic tools (including high frequency ultrasound transducers) as well as the lack of sufficient knowledge in this area. In relation to the above, the symptoms of compression neuropathies were frequently interpreted as a manifestation of pathologies of the lumbar part of the spine or a other orthopedic disease (degenerative or overuse one). Consequently, many patients were treated ineffectively for many months and even, years which led to irreparable neurological changes and changes in the motor organ. Apart from a clinical examination, the diagnostics of entrapment neuropathies of lower limb is currently based on imaging tests (ultrasound, magnetic resonance) as well as functional assessments (electromyography). Magnetic resonance imaging is characterized by a relatively low resolution (as compared to ultrasound) which results in limited possibilities of morphological evaluation of the visualized pathology. Electromyography allows for the assessment of nerve function, but does not precisely determine the type and degree of change. This article presents examples of the most common entrapment neuropathies of the lower limb concerning the following nerves: sciatic, femoral, lateral femoral cutaneous, obturator, fibular and its branches, tibial and its branches as well as sural. The pathomorphological basis of the neuropathies as well as corresponding ultrasound images are presented in this paper. Attention has been drawn to echogenicity, degree of vascularization and bundle presentation of the trunk of a pathological peripheral nerve. Donaghy, M.; Rushworth, G.; Jacobs, J.M. ) A 58-year-old dental prosthetic technician developed generalized sensorimotor peripheral neuropathy. Neurophysiologic studies showed a generalized sensorimotor neuropathy of axonal degeneration type. Examination of a sural nerve biopsy showed a moderately severe axonal neuropathy with loss of large myelinated fibers and unmyelinated axons. There was evidence of slow ongoing degeneration and considerable fiber regeneration. Electron microscopy showed increased numbers of filaments in a few fibers. These findings show resemblances to the nerve changes caused by another acrylic resin, acrylamide. They suggest that the neuropathy may have been caused by 30 years of occupational cutaneous and inhalational exposure to methyl methacrylate monomer since they excluded other recognized causes of neuropathy. Banach, Marta; Antczak, Jakub; Rola, Rafał Background Myotonic dystrophy (DM) type 1 and type 2 are inherited diseases characterized by myotonia and myopathy. Additional symptoms include, among others, peripheral neuropathy and sleep-related breathing disorders (SRBDs). There is growing evidence for a complex association between DM1 and DM2, which was described in patients with diabetes mellitus and in the general population. In this study, we investigated whether there is an association between peripheral neuropathy and SRBDs also in the population of patients with DM. Methods The study included 16 patients with DM1 (mean age, 37.9±14.1 years; 20–69 years) and eight patients with DM2 (mean age, 47.6±14.1 years; 20–65 years), who underwent a sensory and motor nerve conduction study (NCS) and diagnostic screening for SRBDs. In both groups, the NCS parameters were correlated with respiratory parameters. Results In both groups, the amplitude of the ulnar sensory nerve action potential (SNAP) correlated with the mean arterial oxygen saturation (SaO2). In addition, in the DM2 group, the median SNAP correlated with the mean SaO2. In the DM1 group, the median SNAP and the distal motor latency (DML) of the ulnar nerve correlated with the apnea–hypopnea index, while the oxygen desaturation index correlated with the DML of the tibial nerve and with conduction velocity in the sural nerve. Conclusion Our results indicate a complex association between neuropathy and SRBDs in DM1 and DM2. Axonal degeneration may contribute to nocturnal hypoxemia and vice versa. Neuropathy may contribute to muscle weakness, which in turn may cause respiratory events. PMID:28138246 Dukewich, Matthew; Danesh, Arash; Onyima, Chiemeka; Gupta, Anita Fluoroquinolones are widely prescribed antibiotics, used for various infectious etiologies. These antibiotics carry the possibility of the serious adverse effect of peripheral neuropathy, with a true incidence not known owing to its rare existence. Recently, the Food and Drug Administration (FDA) has required alterations to drug labels to highlight this adverse effect of fluoroquinolones. This is a case report of a single patient at an inpatient neurology service at an urban academic medical center in the United States. The patient is a 20-year-old male, with well-controlled type 1 diabetes mellitus, presenting with a short duration of bilateral lower extremity pain following a 10-day course of levofloxacin for suspected epididymitis. The patient was initially diagnosed with complex regional pain syndrome and treated with a variety of pain medications, including lidocaine infusions, hydromorphone, methadone, and ketamine infusions. After review of the patient's history and limited response to medical management, the patient's condition was reclassified as an adverse effect from fluoroquinolone treatment. Pain of unknown etiology can be perplexing, both for the physician and the patient. Reporting of similar incidents attributed to medication adverse effects will increase the awareness of this type of neuropathy, avoid future cases of misdiagnosis, and enable early detection and treatment. Yoo, Min; Sharma, Neena; Pasnoor, Mamatha; Kluding, Patricia M Diabetic peripheral neuropathy (DPN) is a frequent complication of diabetes and a major cause of morbidity and increased mortality. It is typically characterized by significant deficits in tactile sensitivity, vibration sense, lower-limb proprioception, and kinesthesia. Painful diabetic neuropathy (P-DPN) is a common phenotype of DPN that affects up to one-third of the general diabetic population. P-DPN has been shown to be associated with significant reductions in overall quality of life, increased levels of anxiety and depression, sleep impairment, and greater gait variability. The purpose of this review is to examine proposed mechanisms of P-DPN, summarize current treatment regimen, and assess exercise as a potential therapy for P-PDN. Although exercise has been shown to be an effective therapeutic modality for diabetes, its specific effects on DPN and especially the painful phenotype have not been sufficiently investigated in current literature. Several rodent models and clinical trials have presented promising results in this area, and warrant further investigations examining the effect of exercise on P-DPN. Yoo, Min; Sharma, Neena; Pasnoor, Mamatha; Kluding, Patricia M Diabetic peripheral neuropathy (DPN) is a frequent complication of diabetes and a major cause of morbidity and increased mortality. It is typically characterized by significant deficits in tactile sensitivity, vibration sense, lower-limb proprioception, and kinesthesia. Painful diabetic neuropathy (P-DPN) is a common phenotype of DPN that affects up to one-third of the general diabetic population. P-DPN has been shown to be associated with significant reductions in overall quality of life, increased levels of anxiety and depression, sleep impairment, and greater gait variability. The purpose of this review is to examine proposed mechanisms of P-DPN, summarize current treatment regimen, and assess exercise as a potential therapy for P-PDN. Although exercise has been shown to be an effective therapeutic modality for diabetes, its specific effects on DPN and especially the painful phenotype have not been sufficiently investigated in current literature. Several rodent models and clinical trials have presented promising results in this area, and warrant further investigations examining the effect of exercise on P-DPN. PMID:25360348 Vital, Anne; Lepreux, Sebastien; Vital, Claude Peripheral neuropathy (PN) has been reported in idiopathic and hereditary forms of parkinsonism, but the pathogenic mechanisms are unclear and likely heterogeneous. Levodopa-induced vitamin B12 deficiency has been discussed as a causal factor of PN in idiopathic Parkinson's disease, but peripheral nervous system involvement might also be a consequence of the underlying neurodegenerative process. Occurrence of PN with parkinsonism has been associated with a panel of mitochondrial cytopathies, more frequently related to a nuclear gene defect and mainly polymerase gamma (POLG1) gene. Parkin (PARK2) gene mutations are responsible for juvenile parkinsonism, and possible peripheral nervous system involvement has been reported. Rarely, an association of parkinsonism with PN may be encountered in other neurodegenerative diseases such as fragile X-associated tremor and ataxia syndrome related to premutation CGG repeat expansion in the fragile X mental retardation (FMR1) gene, Machado-Joseph disease related to an abnormal CAG repeat expansion in ataxin-3 (ATXN3) gene, Kufor-Rakeb syndrome caused by mutations in ATP13A2 gene, or in hereditary systemic disorders such as Gaucher disease due to mutations in the β-glucocerebrosidase (GBA) gene and Chediak-Higashi syndrome due to LYST gene mutations. This article reviews conditions in which PN may coexist with parkinsonism. Paxton, Roger J.; Feldman-Kothe, Caitlin; Trabert, Megan K.; Hitchcock, Leah N.; Reiser, Raoul F.; Tracy, Brian L. Introduction The purpose was to determine the effect of peripheral neuropathy (PN) on motor output variability for ankle muscles of older adults, and the relation between ankle motor variability and postural stability in PN patients. Methods Older adults with (O-PN) and without PN (O), and young adults (Y) underwent assessment of standing postural stability and ankle muscle force steadiness. Results O-PN displayed impaired ankle muscle force control and postural stability compared with O and Y groups. For O-PN, the amplitude of plantarflexor force fluctuations was moderately correlated with postural stability under no-vision conditions (r = 0.54, P = 0.01). Discussion The correlation of variations in ankle force with postural stability in PN suggests a contribution of ankle muscle dyscontrol to the postural instability that impacts physical function for older adults with PN. PMID:26284897 Games, Gina; Hutchison, Amber With the prevalence of diabetes mellitus (DM) increasing, pathologic complications such as diabetic peripheral neuropathy (DPN) are also becoming more common. Of those diagnosed with DM, 10% to 20% of patients suffer from painful DPN. Until recently, only pregabalin and duloxetine possessed Food and Drug Administration (FDA) approval for this condition. However, FDA recently approved tapentadol-ER [extended release] (Nucynta ER) for painful DPN. Tapentadol-ER is an opioid analgesic commonly used for the treatment of moderate-to-severe chronic pain that contains a unique dual mechanism acting as both a weak mu-opiod receptor agonist and norepinephine-reuptake inhibitor. It is by way of this unique dual mechanism that allows for effective analgesic effects with increased tolerability. This new FDA approval provides an additional therapeutic option to treat DPN in symptomatic patients. Cohen, Helen S; Mulavara, Ajitkumar P; Peters, Brian T; Sangi-Haghpeykar, Haleh; Kung, Doris H; Mosier, Dennis R; Bloomberg, Jacob J Few tests of functional motor behavior are useful for rapidly screening people for lower extremity peripheral neuropathy. The goal of this study was to improve the widely used tandem walking (TW) test. We tested "normal" (control) adult and ambulatory patients with peripheral neuropathy (PN) with their eyes open and eyes closed while they performed TW on industrial carpeting in sock-covered feet. Each subject wore a torso-mounted inertial motion unit to measure kinematic data. The data of subjects with PN also were compared with historical data on patients with vestibular impairments. The normal and PN groups differed significantly on TW and on the number of steps completed. PN and vestibular impairments data also differed significantly on both visual conditions. Kinematic data showed that patients with PN were more unstable than normal patients in the group. For the number of steps taken during the eyes open condition, receiver operating characteristic (ROC) values were only 0.81 and for the number of steps taken during the eyes closed condition, ROC values were 0.88. Although not optimal, this ROC value is better. Sensitivity and specificity at a cutoff of two steps were 0.81 and 0.92, respectively, and at a cutoff of three steps were 0.86 and 0.75, respectively. ROC values for kinematic data were <0.8, and when combined with the ROC value for the number of steps, the total ROC value did not improve appreciably. Although not ideal for screening patients who may have PN, counting the number of steps during TW is a quick and useful clinical test. TW is most sensitive to patients with PN when they are tested with eyes closed. Adams, Alyce S; Bayliss, Elizabeth A; Schmittdiel, Julie A; Altschuler, Andrea; Dyer, Wendy; Neugebauer, Romain; Jaffe, Marc; Young, Joseph D; Kim, Eileen; Grant, Richard W Challenges to effective pharmacologic management of symptomatic diabetic peripheral neuropathy include the limited effectiveness of available medicines, frequent side effects, and the need for ongoing symptom assessment and treatment titration for maximal effectiveness. We present here the rationale and implementation challenges of the Diabetes Telephone Study, a randomized trial designed to improve medication treatment, titration, and quality of life among patients with symptomatic diabetic peripheral neuropathy. We implemented a pragmatic cluster randomized controlled trial to test the effectiveness of an automated interactive voice response tool designed to provide physicians with real-time patient-reported data about responses to newly prescribed diabetic peripheral neuropathy medicines. A total of 1834 primary care physicians treating patients in the diabetes registry at Kaiser Permanente Northern California were randomized into the intervention or control arm. In September 2014, we began identification and recruitment of patients assigned to physicians in the intervention group who receive three brief interactive calls every 2 months after a medication is prescribed to alleviate diabetic peripheral neuropathy symptoms. These calls provide patients with the opportunity to report on symptoms, side effects, self-titration of medication dose and overall satisfaction with treatment. We plan to compare changes in self-reported quality of life between the intervention group and patients in the control group who receive three non-interactive automated educational phone calls. Successful implementation of this clinical trial required robust stakeholder engagement to help tailor the intervention and to address pragmatic concerns such as provider time constraints. As of 27 October 2015, we had screened 2078 patients, 1447 of whom were eligible for participation. We consented and enrolled 1206 or 83% of those eligible. Among those enrolled, 53% are women and the mean age Adams, Alyce S; Bayliss, Elizabeth; Schmittdiel, Julie A; Altschuler, Andrea; Dyer, Wendy; Neugebauer, Romain; Jaffe, Marc; Young, Joseph; Kim, Eileen; Grant, Richard W Background Challenges to effective pharmacologic management of symptomatic diabetic peripheral neuropathy include the limited effectiveness of available medicines, frequent side effects, and the need for ongoing symptom assessment and treatment titration for maximal effectiveness. We present here the rationale and implementation challenges of the Diabetes Telephone Study, a randomized trial designed to improve medication treatment, titration and quality of life among patients with symptomatic diabetic peripheral neuropathy. Methods We implemented a pragmatic cluster randomized controlled trial to test the effectiveness of an automated interactive voice response tool designed to provide physicians with real-time patient-reported data about responses to newly prescribed diabetic peripheral neuropathy medicines. 1,830 primary care physicians treating patients in the diabetes registry at Kaiser Permanente Northern California were randomized into the intervention or control arm in September 2014. Patients assigned to physicians in the intervention group receive three brief interactive calls every 2 months after a medication is prescribed to alleviate diabetic peripheral neuropathy symptoms. These calls provide patients with the opportunity to report on symptoms, side effects, self-titration of medication dose and overall satisfaction with treatment. We plan to compare changes in self-reported quality of life between the intervention group and patients in the control group who receive three non-interactive automated educational phone calls. Results Successful implementation of this clinical trial required robust stakeholder engagement to help tailor the intervention and to address pragmatic concerns such as provider time constraints. As of October 27, 2015, we had screened 2,078 patients, 1,447 of whom were eligible for participation. We consented and enrolled 1,206 or 83% of those eligible. Among those enrolled, 53% are women and the mean age is 67 (sd 12). The racial Ahmed, Marwan A; Muntingh, George; Rheeder, Paul The association between long-term metformin use and low vitamin B12 levels has been proven. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed considerable variation among the studies. The potential of the deficiency to cause or worsen peripheral neuropathy in type-2 diabetes mellitus (T2DM) patients has been investigated with conflicting results. The aim of the study was to investigate: 1) the prevalence of vitamin B12 deficiency in T2DM patients on metformin; 2) the association between vitamin B12 and peripheral neuropathy; 3) and the risk factors for vitamin B12 deficiency in these patients. In this cross-sectional study, consecutive metformin-treated T2DM patients attending diabetes clinics of two public hospitals in South Africa were approached for participation. Participation included measuring vitamin B12 levels and assessing peripheral neuropathy using Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire. The prevalence of vitamin B12 deficiency (defined by concentrations <150 pmol/L) was determined. Those with NTSS-6 scores >6 were considered to have peripheral neuropathy. The relationship between vitamin B12 and peripheral neuropathy was investigated when the two variables were in the binary and continuous forms. Multiple logistic regression was used to determine risk factors for vitamin B12 deficiency. Among 121 participants, the prevalence of vitamin B12 deficiency was 28.1 %. There was no difference in presence of neuropathy between those with normal and deficient vitamin levels (36.8 % vs. 32.3 %, P = 0.209). Vitamin B12 levels and NTSS-6 scores were not correlated (Spearman's rho =0.056, P = 0.54). HbA1c (mmol/mol) (OR = 0.97, 95 % CI: 0.95 to 0.99, P = 0.003) and black race (OR = 0.34, 95 % CI: 0.13 to 0.92, P = 0.033) were risk factors significantly associated with vitamin B12 deficiency. Metformin daily dose (gram) showed borderline significance (OR = 1.96, 95 % CI: 0.99 to 3 Mozdzanowski, Christopher; Perdrizet, George A Otic barotrauma (OBT) is an adverse event seen in patients receiving hyperbaric oxygen (HBO2) therapy. After encountering a case of painless tympanic perforation during HBO2 therapy of a diabetic patient with the diagnosis of neuropathic Wagner Grade III foot ulcer, we hypothesized that peripheral neuropathy of the lower extremity may be associated with an increased risk of asymptomatic OBT during HBO2 therapy. The medical records of all HBO2 patients during a one-year period of time were reviewed. Subjects were selected based on otoscopic documentation of OBT and divided into two groups based on the presence or absence of lower extremity peripheral neuropathy. Time to therapeutic compression, presence or absence of ear-related symptoms and modified Teed (mTeed) scores were compared between the two groups. A total of 38 patients with OBT, 18 neuropathic and 20 non-neuropathic, were identified. Asymptomatic OBT occurred more frequently in the neuropathic vs. non-neuropathic group (56% vs. 5%, p < 0.001). mTeed scores were significantly greater in the neuropathic vs. non-neuropathic group (mTeed 1, 30% vs. 61%; mTeed 2, 65% vs. 36%; mTeed 3, 4% vs. 3%; p = 0.032). Mean compression times were shorter in the neuropathic vs. non-neuropathic group (10. 5 +/- 1.8 vs. 14.4 +/- 3.3 minutes, p < 0.001). The presence of peripheral neuropathy of the lower extremity may be associated with a significantly greater incidence of asymptomatic otic barotrauma during HBO2 therapy. Kim, Min-jung; Sung, Hyunkyung; Hong, Kwon-eui Objectives: This study aimed to evaluate the evidence available in the literature for the safety and efficacy of Dioscoreae Rhizoma(DR) for the treatment of peripheral neuropathy. Methods: Literature searches were performed in MEDLINE and three Korean medical databases up to April 2013. All studies evaluating the effects on peripheral neuropathy or the safety of DR monopreparations were considered. Results: Three studies - DR extract per os (po) on diabetic neuropathy in mice, DR extract injection on the peripheral sciatic nerve after crush injury in rats and DR extract injection to patients with peripheral facial paralysis proved that DR treatments were effective for the treatment of nerve injuries. Conclusions: In conclusion, we found the DR has a strong positive potential for the treatment of peripheral neuropathy, but studies addressing direct factors related to the nerve still remain insufficient. PMID:25780670 Klein, Sandra E; Chu, Jennifer; McCormick, Jeremy J; Johnson, Jeffrey E The foot and ankle surgeon can see peripheral neuropathy in the treatment of foot and ankle conditions. The purpose of this study was (1) to evaluate the demographics and presenting complaints of patients diagnosed with idiopathic peripheral neuropathy during an examination by a foot and ankle surgeon and (2) to identify the type and frequency of subsequent diagnosis of medical causes of neuropathy. This was a retrospective study of patients diagnosed with idiopathic peripheral neuropathy in our practice between January 1997 and December 2008. Ninety-five patients were identified, and demographic data, presenting complaints, and medical comorbidities were extracted from the medical record. Examination findings of decreased sensation to Semmes Weinstein 5.07 monofilament testing were documented, and electromyogram and nerve conduction study results were reviewed when available. Laboratory values were noted, as were neurologic evaluations performed to diagnose medical conditions associated with peripheral neuropathy. The most common presentation was foot pain, in 36 patients (38%). Ninety-one patients had Semmes Weinstein 5.07 monofilament testing, with loss of protective sensation reported in 75 of the 91 tested (82%). Only 30 of the 95 patients had electromyogram and nerve conduction study results available, with a test positive for peripheral neuropathy in 20 of the 30 tested. Thirty-two patients were evaluated by a neurologist. A specific cause was identified in 12 of the 32 seen by a neurologist. Of the total group of 95 patients, 31 patients (33%) were diagnosed with a condition that may be associated with peripheral neuropathy. Thirty-three percent of the patients presenting to our clinic and given a diagnosis of idiopathic peripheral neuropathy were ultimately diagnosed with a medical cause of neuropathy-most commonly, diabetes. For those patients with idiopathic neuropathy, a spectrum of disease was encountered, including pain, ulcer, infection, and Charcot Ewertz, Marianne; Qvortrup, Camilla; Eckhoff, Lise Chemotherapy with taxanes and platinum compounds has resulted in substantial survival benefits both in adjuvant and metastatic settings. However, as a side effect, such chemotherapy may cause peripheral neuropathy (CIPN) which may result in discontinuation of treatment, and if it persists after treatment completion, has a negative impact on quality of life (QoL). Symptoms of CIPN are sensory, like pain, numbness, and tingling, typically located in the hands and feet. For oxaliplatin, there is an acute form of CIPN, resulting in paraesthesias in the mouth and throat during or shortly after the infusion triggered by exposure to cold. Risks factors for CIPN include preexisting neuropathy, either from treatment with other neurotoxic agents, or from comorbid conditions. The incidence of CIPN is related to dose per cycle, cumulative dose, and duration of infusion. While cisplatin-induced neuropathy is irreversible, CIPN induced by taxanes may persist for several years in about 30% of patients. Evidence from the literature is suggestive that CIPN is likely to be negatively associated with QoL. No agents have been identified to be recommended for the prevention of CIPN. For treatment of CIPN, the best available data supports a moderate recommendation for treatment with duloxetine and evidence is inconclusive regarding the use of tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine. Research is still needed to predict which patients are at high risk of developing CIPN during treatment and in whom CIPN will persist after completion of chemotherapy. Yeh, Tzu-min; Evans, Scott R; Gulick, Roy M; Clifford, David B To evaluate the effect of vicriviroc (VCV) on peripheral neuropathy (PN), the most prevalent neurological complication of HIV infection in HIV-1-infected treatment- experienced population. A5211 is a randomized placebo- controlled trial evaluating VCV in treatment-experienced HIV participants failing current therapy. Participants were randomized to VCV (5, 10, or 15 mg) or placebo with optimized ritonavir-containing antiretroviral therapy and followed for 48 weeks. PN was defined as having at least mild loss of vibration bilaterally or ankle reflexes absent or hypoactive bilaterally. We estimated the association between VCV (pooled doses) with PN using a logistic generalized estimating equation. Additional outcomes included symptomatic neuropathy (SPN), painful neuropathy (PPN), and neuropathic signs and symptoms. 118 participants (92% male, 65% white, median age of 46 years, median baseline CD4 139, median HIV-1 RNA 4.58 log) were randomized (90 on VCV and 28 on placebo). VCV therapy did not result in a statistically significant difference relative to placebo in PN (OR = 1.52; P = .39; 95% CI 0.59, 3.90) after controlling for baseline PN status and baseline neurotoxic nucleoside reverse transcriptase inhibitor(s) use. Treatment with VCV over 48 weeks failed to result in statistically significant effect on PN in treatment-experienced participants with HIV infection relative to placebo, however potentially important effects cannot be ruled out. Lidove, O; Cacoub, P; Maisonobe, T; Servan, J; Thibault, V; Piette, J; Leger, J OBJECTIVES—To describe cases of peripheral neuropathy associated with chronic hepatitis C virus infection without mixed cryoglobulinaemia. METHODS—Four cases of peripheral neuropathy associated with chronic hepatitis C virus infection with persistent negativity of mixed cryoglobulinaemia were found. RESULTS—All patients had small increases of transaminase levels and a positive viraemia. Liver biopsy showed chronic active hepatitis in all but one case (Knodell 4-9, Metavir A0F0-A3F3). Neuromuscular biopsy showed axonal neuropathy associated with lymphoid infiltrates around small vessels in two cases. Rheumatoid factor was always negative and C4 complement level was always normal. In three patients, neuropathy improved with interferon α, interferon α + ursodesoxycholic acid, or steroids + plasma exchange. CONCLUSION—Peripheral neuropathy may be associated with hepatitis C virus infection without mixed cryoglobulinaemia. PMID:11171696 Mathew, L; Talbot, K; Love, S; Puvanarajah, S; Donaghy, M Vasculitis of the peripheral nervous system (PNS) is rare. There are no controlled treatment trials, and clinical practice is guided by experience from case series and indirectly by analogy with systemic vasculitis. We identified patients (n=212) with possible vasculitic peripheral neuropathy (VPN) from the neuropathology and neurophysiology records of two centres over 28 years. Case-notes were available for 181, from which, 106 cases of clinicopathological VPN were identified. Adequate treatment data were available in 100; follow-up data, in 93. Of 106 cases, 95 had systemic vasculitis and 11 had vasculitis confined to the PNS. Pharmacological treatment (94/100 cases) was corticosteroid-based, and included cyclophosphamide in 54; 17 received additional agents. Initial stabilization was achieved in all but six. One-year survival was 90.3%. Of the nine who died in the first years (mean age 73 years), seven had received cyclophosphamide, and all but two had severe, multisystem vasculitis. The neurological relapse rate was 10%. Only one relapse occurred after cyclophosphamide treatment. Outcome was reported as good in 72% (78% in those who relapsed). Death and relapse were infrequent in treated patients. Relapse occurred almost exclusively in patients treated with prednisolone alone. Aggressive early treatment with cyclophosphamide may prevent relapse. The current management approach to VPN appears largely effective, especially if cyclophosphamide is used. Bakogeorgos, Marios; Georgoulias, Vassilis Chemotherapy-induced peripheral neuropathy (CIPN), a common adverse effect of several chemotherapeutic agents, has a significant impact on quality of life and may even compromise treatment efficacy, requiring chemotherapy dose reduction or discontinuation. CIPN is predominantly related with sensory rather than motor symptoms and the most common related cytotoxic agents are platinum compounds, taxanes and vinca alkaloids. CIPN symptoms may resolve after treatment cessation, but they can also be permanent and continue for years. Areas covered: We present an overview of CIPN pathophysiology, clinical assessment, prevention and treatment identified through a Pubmed search. Expert commentary: No substantial progress has been made in the last few years within the field of prevention and/or treatment of CIPN, in spite of remarkable efforts. Continuous research could expand our knowledge about chemotherapeutic-specific neuropathic pathways and eventually lead to the conception of innovative and targeted agents for the prevention and/or treatment of this debilitating chemotherapy adverse effect. Wang, Qing-hua; Zhong, Zhi-xia; Chen, Jing-jing; Xie, Ke-qin; Zhao, Xiu-lan To observe the peripheral neurotoxicity of 1-bromopropane (1-BP) by developing an animal model of peripheral neuropathy through oral administration of 1-BP. Forty male Wistar rats were randomly and equally divided into low-dose group (200 mg/kg), medium-dose group (400 mg/kg), high-dose group (800 mg/kg), and control group. The rats in the low-dose, medium-dose, and high-dose groups were orally given 1-BP (dissolved in corn oil), while the rats in the control group were orally given an equal volume of corn oil. The oral administration (0.2 ml/100 g BW) was performed once per day, 5 days per week, for 16 consecutive weeks. Neurobehavioral indices including gait score, hindlimb grip strength, and hindlimb landing foot splay were recorded periodically. Hematological and biochemical parameters were also measured during and after 1-BP exposure. The gait scores were significantly higher in the high-dose group (after 8 ∼ 16 weeks of 1-BP exposure), medium-dose group (after 14 ∼ 16 weeks of 1-BP exposure), and low-dose group (after 15 ∼ 16 weeks of 1-BP exposure) than in the control group (P < 0.05, P < 0.01). Compared with the control group, the high-dose group showed significantly decreased hindlimb grip strength after 9, 12, and 14 weeks of 1-BP exposure (P < 0.05, P < 0.01), with the hindlimbs paralyzed after 16 weeks of 1-BP exposure. After 16 weeks of 1-BP exposure, the hindlimb grip strengths of rats in the medium-dose and low-dose groups were decreased to 72.6% and 91.2% of the control value (P < 0.01, P < 0.05). Compared with the control group, the high-dose group showed significantly increased hindlimb landing foot splay after 12, 14, and 16 weeks of 1-BP exposure, and the medium-dose group showed significantly increased hindlimb landing foot splay after 14 and 16 weeks of 1-BP exposure (P < 0.05, P < 0.01). The high-dose and medium-dose groups showed significantly higher serum alanine aminotransferase (ALT) activity than the control group after 8 weeks of Background We hypothesized that a wide range of surgical procedures may be complicated by neuropathies, not just in close proximity but also remote from procedural sites. The aim of this study was to classify post-operative neuropathies and the procedures associated with them. Methods We retrospectively identified 66 patients diagnosed with post-procedure neuropathies between January 2005 and June 2008. We reviewed their referral cards and medical records for patient demographics, information on procedures, symptoms, as well as clinical and neurophysiological findings. Results Thirty patients (45.4%) had neuropathies remote from procedural sites and 36 patients (54.5%) had neuropathies in close proximity to procedural sites. Half of the remote neuropathies (15/30) developed following relatively short procedures. In 27% of cases (8/30) remote neuropathies were bilateral. Seven patients developed neuropathies remote from operative sites following hip arthroplasties (7/30: 23.3%), making hip arthroplasty the most common procedure associated with remote neuropathies. Sciatic neuropathies due to hip arthroplasty (12/36, 33.3%) accounted for the majority of neuropathies occurring in close proximity to operative sites. Five medial cutaneous nerve of forearm neuropathies occurred following arterio-venous fistula (AVF) formation. Conclusions An array of surgical procedures may be complicated by neuropathy. Almost half of post-procedure neuropathies occur remote from the site of procedure, emphasizing the need to try to prevent not just local, but also remote neuropathies. Mechanical factors and patient positioning should be considered in the prevention of post-operative neuropathies. There is a possible association between AVF formation and medial cutaneous nerve of forearm neuropathy, which requires further study for validation. PMID:20398427 Kles, Keri A; Vinik, Aaron I Worldwide, diabetes and its complications are major causes of morbidity, decreased quality of life, mortality and increasing health care costs. Patients with diabetes attempt to control blood pressure, lipids and blood glucose levels to decrease their risk of macrovascular and microvascular complications, such as diabetic peripheral neuropathy (DPN). Even with control of these risk factors for vascular disease, many patients still develop complications. Targeted therapies to the underlying mechanisms of diabetic neuropathy are essential to slow the progression of the disease. This review describes the signs, symptoms and diagnosis of DPN. Additionally, new therapies and the complex etiology that contributes to the development of diabetic neuropathy are described (oxidative stress, hyperglycemia, advanced glycated end products, autoimmunity, neurotrophic factors and protein kinase C beta). Jember, Gashaw; Melsew, Yayehirad Alemu; Fisseha, Berihu; Sany, Kedir; Gelaw, Asmare Yitayeh; Janakiraman, Balamurugan Diabetic sensory neuropathy is a common form of microvascular complication among diabetic patients. The swiftly growing population of people living with diabetes in Ethiopia and lack of elaborated scientific data on peripheral sensory neuropathy among diabetic population in Ethiopia prompted this work. This study was set out to assess the enormity and associated factors of peripheral sensory neuropathy among diabetes patients attending chronic illness clinic of Felege Hiwot Regional Referral Hospital, Bahr Dar, Northwest Ethiopia. An institution based cross-sectional study was conducted at Felege Hiwot Referral Hospital chronic illness clinic using Michigan neuropathy screening instrument tool for diabetic peripheral sensory neuropathy on 408 diabetic patients during 2016. Data were collected using interview, patient record review, anthropometric measurements and physical examination. Both bivariate and multivariate binary logistic regression was employed to identify factors associated with peripheral sensory neuropathy. Odds ratios with their 95% CI and P value less than 0.05 used to determine statistically significant associations. A total of 368 patients were included with the mean age of 49 ± 14.3 years. The overall prevalence of Peripheral Sensory Neuropathy was found to be 52.2%. The major associated factors identified by multivariate analysis were age >50 years: AOR: 3.0 CI [1.11, 7.89]; overweight and obese: AOR: 7.3 CI [3.57, 14.99]; duration of DM: AOR: 3.4 CI [1.75, 6.60]; not involved in physical exercise: AOR: 4.8 CI [1.90, 7.89]; male gender: AOR: 2.4 CI [1.18, 5.05]. Almost half of the diabetic patients who attended Felege Hiwot regional referral hospital during study period were found to present with peripheral sensory neuropathy. Socio-demographic and bio characteristics like patients age, Body Mass Index, level of physical activity and marital status were significantly associated with diabetic peripheral sensory neuropathy. de Carvalho Barbosa, Mariana; Kosturakis, Alyssa K; Eng, Cathy; Wendelschafer-Crabb, Gwen; Kennedy, William R; Simone, Donald A; Wang, Xin S; Cleeland, Charles S; Dougherty, Patrick M Peripheral neuropathy caused by cytotoxic chemotherapy, especially platins and taxanes, is a widespread problem among cancer survivors that is likely to continue to expand in the future. However, little work to date has focused on understanding this challenge. The goal in this study was to determine the impact of colorectal cancer and cumulative chemotherapeutic dose on sensory function to gain mechanistic insight into the subtypes of primary afferent fibers damaged by chemotherapy. Patients with colorectal cancer underwent quantitative sensory testing before and then prior to each cycle of oxaliplatin. These data were compared with those from 47 age- and sex-matched healthy volunteers. Patients showed significant subclinical deficits in sensory function before any therapy compared with healthy volunteers, and they became more pronounced in patients who received chemotherapy. Sensory modalities that involved large Aβ myelinated fibers and unmyelinated C fibers were most affected by chemotherapy, whereas sensory modalities conveyed by thinly myelinated Aδ fibers were less sensitive to chemotherapy. Patients with baseline sensory deficits went on to develop more symptom complaints during chemotherapy than those who had no baseline deficit. Patients who were tested again 6 to 12 months after chemotherapy presented with the most numbness and pain and also the most pronounced sensory deficits. Our results illuminate a mechanistic connection between the pattern of effects on sensory function and the nerve fiber types that appear to be most vulnerable to chemotherapy-induced toxicity, with implications for how to focus future work to ameloirate risks of peripheral neuropathy. Reeves, Brandi N; Dakhil, Shaker R; Sloan, Jeff A; Wolf, Sherry L; Burger, Kelli N; Kamal, Arif; Le-Lindqwister, Nguyet A; Soori, Gamini S; Jaslowski, Anthony J; Kelaghan, Joseph; Novotny, Paul J; Lachance, Daniel H; Loprinzi, Charles L Paclitaxel causes an acute pain syndrome (P-APS), occurring within days after each dose and usually abating within days. Paclitaxel also causes a more classic peripheral neuropathy, which steadily increases in severity with increasing paclitaxel total doses. Little detail is available regarding the natural history of these 2 syndromes, or any relationship between them, although a recent publication does provide natural history data about weekly paclitaxel, supporting an association between the severity of P-APS and eventual peripheral neuropathy symptoms. Patients entering this study were about to receive paclitaxel and carboplatin every 3 weeks. Daily questionnaires were completed for the first week after every chemotherapy dose, and European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Chemotherapy-Induced Peripheral Neuropathy 20-item instruments were completed weekly. The P-APS severity peaked on day 4 after the initial chemotherapy dose, with 12%, 29%, 23%, and 36% of patients having maximal pain scores of 0, 1 to 4, 5 or 6, or 7 to 10 during the first week after the first dose of therapy, respectively. Patients with P-APS scores of 0 to 4 with the first dose of chemotherapy had less eventual sensory neuropathy than did patients with P-APS scores of 5 to 10 (P = 0.001). With regard to the more peripheral neuropathy, sensory neuropathy was more problematic than was either motor or autonomic neuropathy. Numbness and tingling were more common components of the sensory neuropathy than was pain. Patients with worse P-APS severities appear to have more eventual chemotherapy-induced peripheral neuropathy. This provides support for the concept that P-APS is a form of nerve pathology. Copyright © 2012 American Cancer Society. Mohrmann, Caroline; Armer, Jane; Hayashi, Robert J Children treated for cancer are exposed to a variety of chemotherapeutic agents with known toxicity to the peripheral nervous system. The side effect of peripheral neuropathy can cause changes in sensation, function, and even cause pain. Although peripheral neuropathy is recognized by pediatric oncology nurses as an important and significant side effect, measuring neuropathy can be quite complex for clinical care and research efforts. With more children surviving a cancer diagnosis today, this issue is increasingly important for childhood cancer survivors. This article has reviewed existing literature examining peripheral neuropathy in childhood cancer survivors with particular interest paid to measurement tools available and needs for future research. It is important for nurses to choose appropriate measures for clinical care and research methods in order to have an impact on patients experiencing this condition. Luigetti, M; Sauchelli, D; Primiano, G; Cuccagna, C; Bernardo, D; Lo Monaco, M; Servidei, S Peripheral neuropathy in mitochondrial diseases (MDs) may vary from a subclinical finding in a multisystem syndrome to a severe, even isolated, manifestation in some patients. To investigate the involvement of the peripheral nervous system in MDs extensive electrophysiological studies were performed in 109 patients with morphological, biochemical and genetic diagnosis of MD [12 A3243G progressive external ophthalmoplegia (PEO)/mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), 16 myoclonic epilepsy with ragged-red fibres (MERRF), four mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), 67 PEO with single or multiple deletions of mitochondrial DNA, 10 others]. A neuropathy was found in 49 patients (45%). The incidence was very high in MNGIE (100%), MELAS (92%) and MERRF (69%), whilst 28% of PEO patients had evidence of peripheral involvement. The most frequent abnormality was a sensory axonal neuropathy found in 32/49 patients (65%). A sensory-motor axonal neuropathy was instead detected in 16% of the patients and sensory-motor axonal demyelinating neuropathy in 16%. Finally one Leigh patient had a motor axonal neuropathy. It is interesting to note that the great majority had preserved tendon reflexes and no sensory disturbances. In conclusion, peripheral involvement in MD is frequent even if often mild or asymptomatic. The correct identification and characterization of peripheral neuropathy through electrophysiological studies represents another tile in the challenge of MD diagnosis. © 2016 EAN. Peng, Ling; Ye, Xianghua; Zhou, Yun; Zhang, Junyan; Zhao, Qiong Bortezomib is a proteasome inhibitor which has demonstrated activity against recurrent or newly diagnosed multiple myeloma (MM) and mantle cell lymphoma. Peripheral neuropathy has been described with this agent, although the overall incidence and relative risk remain unclear. We performed a meta-analysis to calculate the incidence of peripheral neuropathy associated with the use of intravenous bortezomib in MM and lymphoma and to compare the relative risk compared with placebo. We searched PubMed, Embase, Cochrane databases, and meeting proceedings from the American Society of Clinical Oncology (ASCO) for relevant clinical trials. Eligible studies included prospective phase 2 and 3 clinical trials with toxicity profile on peripheral neuropathy associated with intravenous bortezomib in patients with MM and lymphoma. Statistical analyses were done to calculate summary incidences, relative risks (RRs), and 95 % confidence intervals (CIs), employing fixed- or random-effects models depending on the heterogeneity of the included studies. Altogether, 34 clinical trials were selected for the meta-analysis, yielding a total of 6492 patients. The incidence of peripheral neuropathy (all grades) was 33.9 % (95 % CI, 29.9-38.5 %) and that of high-grade events was 8.1 % (95 % CI, 6.9-9.4 %). The relative risks of bortezomib-induced peripheral neuropathy compared to placebo were increased for all-grade (RR = 4.89; 95 % CI, 2.52-9.51) and high-grade (RR = 4.53; 95 % CI, 2.04-10.07) peripheral neuropathy (for randomized controlled trials only). Our analysis was also stratified by different underlying diseases, and patients with lymphoma had an increased incidence of all-grade peripheral neuropathy than those with MM when treated with intravenous bortezomib. Treatment with intravenous bortezomib is associated with an increased risk of developing peripheral neuropathy. Yoo, Min; D’Silva, Linda; Martin, Katherine; Sharma, Neena; Pasnoor, Mamatha; LeMaster, Joseph Objective Painful diabetic peripheral neuropathy (DPN) is a common complication of diabetes. While the beneficial effect of exercise on diabetes is well established, its effect specifically on painful DPN has not been thoroughly explored. The objective of this pilot study was to examine the effect of aerobic exercise on pain in people with DPN. Methods Fourteen sedentary individuals (mean age 57±5.11 years) with painful DPN were enrolled in a 16-week, supervised aerobic exercise program. The Brief Pain Inventory-Diabetic Peripheral Neuropathy (BPI-DPN) was used to assess pain intensity (worst, least, average, now) and pain interference with daily life (activity, mood, walk, normal work, relationship, sleep, enjoyment of life) pre- and post -intervention. Body mass index (BMI), maximum oxygen uptake (VO2max), hemoglobin A1c (HbA1c), and blood pressure were also measured pre-and post-intervention as secondary outcomes of interest. Results Significant reductions in pain interference were observed with walking (4.93±3.03 pre to 3.29±2.89 post, p=0.016), normal work (5.39±3.32 pre to 3.79±3.04 post, p=0.032), relationship with others (3.96±3.53 pre to 1.29±1.27 post, p=0.006), sleep (5.11±3.04 pre to 3.5±3.03 post, p=0.02), and the overall pain interference (4.65±2.70 pre to 2.97±2.22 post, p=0.013) following the intervention; however, there was no change in pain intensity. VO2max increased significantly post-intervention (16.02±3.84ml/kg/min pre to 17.18±4.19ml/kg/min, p=0.028), while BMI, HbA1c, and blood pressure remained unchanged. Conclusion These preliminary results suggest that perceived pain interference may be reduced following an aerobic exercise intervention among people with painful DPN, without a change in pain intensity. Further validation by a RCT is needed. PMID:25800666 Background Diabetic Peripheral Neuropathy is one of the most prevalent complications of diabetes mellitus. The development and progression of such complications are responsible for much of the morbidity and mortality. The purpose of this study was to evaluate the effectiveness of Semmes–Weinstein monofilament ten gram in 3, 4, eight and ten points in the screening of diabetic peripheral neuropathy in patients with diabetes mellitus. Methods In a descriptive correlational design, 150 patients with diabetes mellitus were selected using convenience sampling. All patients were evaluated for sensory neuropathy using ten gram Semmes-Weinstein Monofilaments and questionnaire on neuropathy symptoms. In the next phase, nerve conduction velocity was examined. The most common subjective symptoms were paresthesia of both feet, pain in feet, burning sensation in the extremities and numbness in the extremities. Results The results showed that the sensitivity of Monofilament in three and four points were 35.9 to 53.8 present and 38.5 to 51.3 percent respectively. Specificity of Monofilament the same points, were 73.9 to 84.7 and 73 to 87.4 percent respectively. Monofilament sensitivity at eight and ten points were 38.5 to 61.5 and 64.1 to 30.8 percent respectively. Also, specificity of the same points were 77.5 to 95.5 and 64 to 89.2 percent respectively. It was revealed that the difference sensitivity and specificity of Monofilament in three and four points with sensitivity and specificity in eight and ten point is not statistically significant. Conclusions This study showed that Semmes-Weinstein monofilament can easily use as a simple and inexpensive device for screening. Since increasing the number of points it was not significantly difference. Therefore, we suggest that screening for diabetic peripheral neuropathy, especially in large populations to avoid wasting time on Monofilament application, areas like three or four points eight and ten points could be used. PMID Background A major clinical issue affecting 10-40% of cancer patients treated with oxaliplatin is severe peripheral neuropathy with symptoms including cold sensitivity and neuropathic pain. Rat models have been used to describe the pathological features of oxaliplatin-induced peripheral neuropathy; however, they are inadequate for parallel studies of oxaliplatin's antineoplastic activity and neurotoxicity because most cancer models are developed in mice. Thus, we characterized the effects of chronic, bi-weekly administration of oxaliplatin in BALB/c mice. We first studied oxaliplatin's effects on the peripheral nervous system by measuring caudal and digital nerve conduction velocities (NCV) followed by ultrastructural and morphometric analyses of dorsal root ganglia (DRG) and sciatic nerves. To further characterize the model, we examined nocifensive behavior and central nervous system excitability by in vivo electrophysiological recording of spinal dorsal horn (SDH) wide dynamic range neurons in oxaliplatin-treated mice Results We found significantly decreased NCV and action potential amplitude after oxaliplatin treatment along with neuronal atrophy and multinucleolated DRG neurons that have eccentric nucleoli. Oxaliplatin also induced significant mechanical allodynia and cold hyperalgesia, starting from the first week of treatment, and a significant increase in the activity of wide dynamic range neurons in the SDH. Conclusions Our findings demonstrate that chronic treatment with oxaliplatin produces neurotoxic changes in BALB/c mice, confirming that this model is a suitable tool to conduct further mechanistic studies of oxaliplatin-related antineoplastic activity, peripheral neurotoxicity and pain. Further, this model can be used for the preclinical discovery of new neuroprotective and analgesic compounds. PMID:21521528 Santoro, L; Manganelli, F; Briani, C; Giannini, F; Benedetti, L; Vitelli, E; Mazzeo, A; Beghi, E Objective To assess the prevalence of peripheral neuropathy (PN) and its correlation with cryoglobulinemia (CG) in an unselected, untreated referral hepatitis C virus (HCV) population. Patients and Methods Two hundred and thirty four patients (120 women and 114 men) with untreated HCV infection were consecutively enrolled by seven Italian centres. Clinical neuropathy was diagnosed when symptoms and signs of peripheral sensory or motor involvement were present. Median, ulnar, peroneal, and sural nerves were explored in all patients and distal symmetric polyneuropathy was diagnosed when all explored nerves or both lower limb nerves were affected. Mononeuropathy and mononeuropathy multiplex were diagnosed when one nerve or two non‐contiguous nerves with asymmetrical distribution were affected. Screening for CG was done in 191 unselected patients. Results Clinical signs of PN were observed in 25 of the 234 patients (10.6%). Electrophysiological PN was found in 36 (15.3%). CG was present in 56/191 patients (29.3%). The prevalence of CG increased significantly with age (p<0.001) and disease duration (p<0.05). PN was present in 12/56 (21%) patients with CG and 18/135 (13%) without CG (p = NS). PN increased significantly with age (p<0.001) and logistic regression analysis confirmed age as the only independent predictor of PN (OR 1.10 for each year; 95% CI 1.04 to 1.15; p<0.001). Conclusions Electrophysiological examination detected subclinical neuropathy in 11 patients (4.7%). Statistical analysis showed that CG was not a risk factor for PN whereas PN prevalence increased significantly with age. PMID:16464900 Li, Xia; Zhu, Ju; Liu, Na; Liu, Jie; Zhang, Zhecheng Impaired glucose regulation (IGR) is the prestate of diabetes; about 1/3 of IGR patients will develop to diabetes finally. In this study, we investigated the serum tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels in peripheral neuropathy impaired patients with impaired glucose regulation (IGR). A total of 70 IGR patients received the conventional nerve conduction test, including 30 patients with peripheral neuropathy (PN) and 40 patients without peripheral neuropathy (NPN). The other 40 healthy individuals were recruited as controls. The serum TNF-α and IL-6 in IGR patients were higher than in control group, and serum TNF-α and IL-6 levels in IGR-PN group were higher than in IGR-NPN group (27.7 ± 17.8 versus 13.1 ± 6.7 pg/mL and 18.1 ± 17.7 versus 6.4 ± 3.7 pg/mL, resp., both p < 0.05). Multifactors logistic regression analysis showed that TNF-α (OR = 0.893; p = 0.009) was an independent factor affecting whether IGR could combine with peripheral neuropathy. TNF-α and IL-6 could aggregate peripheral neuropathy in impaired glucose regulation patients; TNF-α might be independent risk factor for peripheral neuropathy in glucose regulation impaired patients. Zhu, Ju; Liu, Na; Liu, Jie Impaired glucose regulation (IGR) is the prestate of diabetes; about 1/3 of IGR patients will develop to diabetes finally. In this study, we investigated the serum tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels in peripheral neuropathy impaired patients with impaired glucose regulation (IGR). A total of 70 IGR patients received the conventional nerve conduction test, including 30 patients with peripheral neuropathy (PN) and 40 patients without peripheral neuropathy (NPN). The other 40 healthy individuals were recruited as controls. The serum TNF-α and IL-6 in IGR patients were higher than in control group, and serum TNF-α and IL-6 levels in IGR-PN group were higher than in IGR-NPN group (27.7 ± 17.8 versus 13.1 ± 6.7 pg/mL and 18.1 ± 17.7 versus 6.4 ± 3.7 pg/mL, resp., both p < 0.05). Multifactors logistic regression analysis showed that TNF-α (OR = 0.893; p = 0.009) was an independent factor affecting whether IGR could combine with peripheral neuropathy. TNF-α and IL-6 could aggregate peripheral neuropathy in impaired glucose regulation patients; TNF-α might be independent risk factor for peripheral neuropathy in glucose regulation impaired patients. PMID:28251164 Remiche, G; Kadhim, H; Maris, C; Mavroudakis, N Peripheral neuropathy implies damages to neurons belonging to the peripheral nervous system which includes cranial nerves, spinal nerves' roots, spinal ganglia, nerve trunks and their divisions, and, the autonomic nervous system. Peripheral neuropathies are frequent in the general population (prevalence: 2,4%). We present a review of the recent literature and highlight diagnostic approaches for certain types of neuropathies particularly the most frequent ones or those requiring peculiar attention in first-line medicine. We also present epidemiologic data and data related to sural nerve biopsies from our centre. The determination of the location and the topography of the affected sites, integrated into the global context of the patient, is essential to provide an etiologic diagnosis. The median nerve compression within the carpal tunnel and polyneuropathies are the most frequent forms of peripheral neuropathies. More than one hundred causes of polyneuropathies are described and they are divided into acquired, genetically determined and idiopathic. We highlight a largely adopted diagnostic strategy concerning polyneuropathies and describe the Guillain-Barre syndrome, the alcohol-related polyneuropathy and the controversies about the benefit of the B vitamin therapy and its dangers. At the Hôpital Erasme, since 2008, more than 1372 patients with peripheral neuropathy were identified. Results of sural nerve biopsies performed in seventeen of them do not largely differ from those of other centres of expertise. We conclude that the diagnosis of peripheral neuropathy usually requires the expertise of a neurologist, but, first line caregivers must be able to recognize and refer patient when needed. Mohty, Bilal; El-Cheikh, Jean; Yakoub-Agha, Ibrahim; Moreau, Philippe; Harousseau, Jean-Luc; Mohty, Mohamad In multiple myeloma, peripheral neuropathy has for a long time been considered as mainly secondary to the plasma cell dyscrasia itself. With the advent of new targeted drugs such as thalidomide and bortezomib, the iatrogenic neurotoxicity has become the leading cause of peripheral neuropathy. This review discusses the pathogenesis, incidence, risk factors, diagnosis, characteristics, and management of peripheral neuropathy related to new multiple myeloma drugs, mainly bortezomib and thalidomide. The current knowledge of the pathophysiology of the new forms of peripheral neuropathy is still limited. The mechanisms involved depend on the agents used, patient’s medical history, and duration of exposure and/or treatment doses or sequence. Diagnosis of such peripheral neuropathy is often easier than treatment. A full anamnesis and regular clinical evaluation are necessary. Electrophysiological assessments may support the diagnosis, although their contribution remains insufficient. Complex clinical features may require a specialized neurological assessment within the context of a multi-disciplinary approach. Finally, early detection of peripheral neuropathy and the use of dose adjustment algorithms as in the case of bortezomib, should help reduce the side effects while maintaining anti-tumor efficacy. PMID:20139393 Hosokawa, Toyoshi; Ishikawa, Takeshi; Yagi, Nobuaki; Kokura, Satoshi; Naito, Yuji; Nakanishi, Masayoshi; Kokuba, Yukihito; Otsuji, Eigo; Kuroboshi, Haruo; Taniwaki, Masafumi; Taguchi, Tetsuya; Hosoi, Hajime; Nakamura, Terukazu; Miki, Tsuneharu Objective. To evaluate the efficacy of Goshajinkigan for oxaliplatin-induced peripheral neuropathy in colorectal cancer patients. Patients. Colorectal cancer patients (N = 29) who received ≥4 weeks of Goshajinkigan for oxaliplatin-induced peripheral neuropathy during chemotherapy at Kyoto Prefectural University of Medicine were (Goshajinkigan group) compared to 44 patients who had not received Goshajinkigan during the same period (non-Goshajinkigan group). Main Outcome Measures. The effect of Goshajinkigan was graded as curative, effective, stabilizing, or deleterious. The relationships between the grade of peripheral neuropathy and the dose of oxaliplatin in the Goshajinkigan and non-Goshajinkigan groups were evaluated. Results. The effect of Goshajinkigan on peripheral neuropathy in the Goshajinkigan group was curative, effective, stabilizing, and deleterious in 3.4, 20.7, 69.0, and 6.9% of patients, compared to the effect in the non-Goshajinkigan group (4.5, 15.9, 45.5, and 34.1%). The ratio of deleterious effects was significantly different between these two groups (P = 0.04). A Kaplan-Meier analysis in relation to the cumulative dose of oxaliplatin showed that the incidence of grade 3 peripheral neuropathy tended to be less in the Goshajinkigan group (P = 0.05). There were no significant differences in time to treatment failure and severe adverse events between these two groups. Conclusions. Goshajinkigan prevented exacerbation of oxaliplatin-induced peripheral neuropathy. This trial is registered with UMIN000009956 PMID:24307899 Wong, Raimond; Sagar, Stephen Chemotherapy induced peripheral neuropathy (CIPN) occurs in 10 to 20% of cancer patients treated with neurotoxic chemotherapy. A mixture of sensory, sensorimotor and autonomic nervous system dysfunction can occur, resulting in deterioration in function and worsened quality of life. A major feature is discomfort and pain. Early termination of treatment and dose reduction of chemotherapy may be necessary. The clinical course is variable and depends on the chemotherapy agents and their cumulative dose. Although symptoms can resolve completely, in most patients CIPN is either only partially reversible or completely irreversible. Current management for CIPN is symptomatic using membrane stabilising medications and antidepressants. The use of nerve growth factors is still experimental. Dysaesthesia and pain involving the feet and hands are described in both traditional Chinese medicine (TCM) and Western biomedicine. In TCM, the pathogenesis is related to the inability to direct Qi and Blood to the extremities, and is associated with Qi, Blood, Yang and Kidney deficiencies. Acupuncture is moderately effective in treating diabetic neuropathy. However, to date, there is no report of the usefulness of acupuncture for CIPN. We report the result of a pilot prospective case series of five patients treated with an acupuncture protocol that aims to correct Qi, Blood and Yang deficiencies and directs Qi and Blood to the extremities, with the goal of improving the symptoms of CIPN. The responses were encouraging, and cannot be easily explained by the known neurophysiological mechanisms of acupuncture. Douglas, Darlene S.; Popko, Brian Forward genetics, the phenotype-driven approach to investigating gene identity and function, has a long history in mouse genetics. Random mutations in the mouse transcend bias about gene function and provide avenues towards unique discoveries. The study of the peripheral nervous system is no exception; from historical strains such as the trembler mouse, which led to the identification of PMP22 as a human disease gene causing multiple forms of peripheral neuropathy, to the more recent identification of the claw paw and sprawling mutations, forward genetics has long been a tool for probing the physiology, pathogenesis, and genetics of the PNS. Even as spontaneous and mutagenized mice continue to enable the identification of novel genes, provide allelic series for detailed functional studies, and generate models useful for clinical research, new methods, such as the piggyBac transposon, are being developed to further harness the power of forward genetics. PMID:18481175 Sheshah, Eman; Madanat, Amal; Al-Greesheh, Fahad; Al-Qaisi, Dalal; Al-Harbi, Mohammad; Aman, Reem; Al-Ghamdi, Abdul Aziz; Al-Madani, Khaled Sudomotor dysfunction is manifested clinically as abnormal sweating leading to dryness of feet skin and increased risk of foot ulceration. The aim of this study was to test the performance of foot electrochemical skin conductance (ESC) to detect diabetic peripheral neuropathy and the risk of foot ulceration against traditional methods in Saudi patients with diabetes mellitus. This cross-sectional study was conducted on 296 Saudi patients with diabetes mellitus. Painful neuropathic symptoms were evaluated using the neuropathy symptom score (NSS). The risk of foot ulceration and diabetic peripheral neuropathy were determined using the neuropathy disability score (NDS). Vibration perception threshold (VPT) was assessed using neurothesiometer. Neurophysiological assessment of the right and left sural, peroneal and tibial nerves was performed in 222 participants. Diabetic peripheral neuropathy was defined according to the definition of the American Academy of Neurology. ESC was measured with Sudoscan. Feet-ESC decreased as the scores of sensory and motor function tests increased. Feet-ESC decreased as the NSS, NDS and severity of diabetic peripheral neuropathy increased. Sensitivity of feet-ESC < 50μS to detect diabetic peripheral neuropathy assessed by VPT ≥ 25 V, NDS ≥ 3, NDS ≥ 6 was 90.1, 61 and 63.8 % respectively and specificity 77, 85 and 81.9 % respectively. Sensitivity of feet-ESC < 70μS to detect diabetic peripheral neuropathy assessed by VPT ≥ 25 V, NDS ≥ 3, NDS ≥ 6 was 100, 80.6 and 80.9 % respectively. Sensitivity and specificity of feet-ESC < 70μS to detect confirmed-diabetic peripheral neuropathy were 67.5 and 58.9 % respectively. Sudoscan a simple and objective tool can be used to detect diabetic peripheral neuropathy and the risk of foot ulceration among patients with diabetes mellitus. Prospective studies to confirm our results are warranted. Kiser, Deleslie W; Greer, Tara B; Wilmoth, Margaret C; Dmochowski, Jacek; Naumann, R Wendel To analyze the incidence of chemotherapy-induced neuropathy in a set of patients with gynecologic cancer who were treated with known neurotoxic agents, to identify correlative factors related to patients' experience of neuropathy, and to analyze providers' assessment and treatment of neuropathy. Observational descriptive study of patient-reported neuropathy using a retrospective chart analysis. A hospital-based outpatient infusion center in the southeastern United States. A convenience sample of 171 patients with gynecologic cancer for a total of 302 chemotherapy treatments. A mixed model and compound symmetry covariance matrix was used to adjust for correlations between neuropathy treatment scores and patients who completed more than one chemotherapy cycle. Backward elimination method was used to determine the final model. Functional Assessment of Cancer Treatment/Gynecologic Oncology Group-Neuropathy Treatment scores, patients' demographic information, past medical history, and chemotherapy history. Patients who were physically shorter and heavier than the average population had the highest rating of neuropathy. Patients who were treated with nontaxane and platinum therapies had less neuropathy than patients who were treated with first-line taxanes and platinums. Neuropathy was noted by providers early in the course of treatment, and providers' grading was consistent with the patients' scoring. First-line treatments for gynecologic malignancies resulted in the highest neuropathy scores; however, patients who had received previous treatment with taxane and platinum therapies had lower neuropathy scores than patients currently receiving taxanes and platinums, suggesting that neuropathy improved after completion of first-line therapy and that second-line therapies were not necessarily correlative with worsening scores. Nurses must educate patients about symptoms of neuropathy and the need to report symptoms. Nurses must recognize patients at highest risk for Ding, Jie; Cheung, Carol Y.; Ikram, M. Kamran; Zheng, Ying-Feng; Cheng, Ching-Yu; Lamoureux, Ecosse L.; Tai, E. Shyong; Subramaniam, Tavintharan; Wong, Tien Yin OBJECTIVE To examine the association between early retinal arteriolar abnormalities and diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS Data from 608 people (aged 40–80 years) with diabetes from the population-based Singapore Malay Eye Study were analyzed. Participants underwent binocular two-field digital retinal photography and quantitative sensory testing. DPN was defined as an abnormal response to a monofilament or neurothesiometer test. Quantitative changes of retinal vascular caliber and arteriolar bifurcation geometry were measured using a computer-based program. Qualitative retinal signs of retinopathy and retinal arteriolar wall signs were graded by standardized methods. RESULTS DPN was present in 155 people (25.5%). After adjusting for age, sex, diabetes duration, HbA1c, cardiovascular risk factors, antihypertensive medication use, and peripheral arterial disease, people with suboptimal arteriolar caliber (odds ratio 1.94 [95% CI 1.22–3.10]), larger arteriolar branching coefficient (1.58 [1.03–2.42]), diabetic retinopathy (1.82 [1.20–2.75]), and focal arteriolar narrowing (2.92 [1.48–5.76]) were more likely to have DPN. Participants with a greater number of retinal microvascular signs were more likely to have DPN than those without retinal changes (6.11 [2.11–17.71] for two or more signs and 3.47 [1.18–10.21] for one sign compared with none). CONCLUSIONS Individuals with diabetes with early retinal arteriolar abnormalities are more likely to have DPN, independent of hyperglycemia and major vascular risk factors. These data support the hypothesis that early microvascular dysfunction, evident in the retina, is an independent risk factor for DPN. PMID:22374638 Ding, Jie; Cheung, Carol Y; Ikram, M Kamran; Zheng, Ying-Feng; Cheng, Ching-Yu; Lamoureux, Ecosse L; Tai, E Shyong; Subramaniam, Tavintharan; Wong, Tien Yin To examine the association between early retinal arteriolar abnormalities and diabetic peripheral neuropathy (DPN). Data from 608 people (aged 40-80 years) with diabetes from the population-based Singapore Malay Eye Study were analyzed. Participants underwent binocular two-field digital retinal photography and quantitative sensory testing. DPN was defined as an abnormal response to a monofilament or neurothesiometer test. Quantitative changes of retinal vascular caliber and arteriolar bifurcation geometry were measured using a computer-based program. Qualitative retinal signs of retinopathy and retinal arteriolar wall signs were graded by standardized methods. DPN was present in 155 people (25.5%). After adjusting for age, sex, diabetes duration, HbA(1c), cardiovascular risk factors, antihypertensive medication use, and peripheral arterial disease, people with suboptimal arteriolar caliber (odds ratio 1.94 [95% CI 1.22-3.10]), larger arteriolar branching coefficient (1.58 [1.03-2.42]), diabetic retinopathy (1.82 [1.20-2.75]), and focal arteriolar narrowing (2.92 [1.48-5.76]) were more likely to have DPN. Participants with a greater number of retinal microvascular signs were more likely to have DPN than those without retinal changes (6.11 [2.11-17.71] for two or more signs and 3.47 [1.18-10.21] for one sign compared with none). Individuals with diabetes with early retinal arteriolar abnormalities are more likely to have DPN, independent of hyperglycemia and major vascular risk factors. These data support the hypothesis that early microvascular dysfunction, evident in the retina, is an independent risk factor for DPN. Kärvestedt, Lars; Mårtensson, Eva; Grill, Valdemar; Elofsson, Stig; von Wendt, Gunvor; Hamsten, Anders; Brismar, Kerstin OBJECTIVE—To assess associations between peripheral sensory neuropathy (PSN) and other diabetes-related complications. RESEARCH DESIGN AND METHOD—In an area-based cohort of type 2 diabetic subjects, we investigated 156 subjects (age 61.7 ± 7.2 years and diabetes duration 7.0 ± 5.7 years) by questionnaires, clinical examinations, blood and urine sampling, and review of medical records. RESULTS—Prevalence of PSN, assessed by monofilament and neurothesiometer testing, increased with severity of retinopathy (50% frequency in moderate and 100% in severe or proliferative retinopathy; P = 0.02). Vibration perception threshold was higher in subjects with retinopathy (25.6 ± 8.9 vs. 20.5 ± 8.9 V; P = 0.007). PSN was more common in subjects with overt nephropathy, with higher vibration perception thresholds, than in subjects without overt nephropathy. Subjects with PSN but no retinopathy had twice the prevalence of peripheral vascular disease (PVD) (52%) as subjects with both PSN and retinopathy (19%; P = 0.05). In subjects with PSN alone, PVD was three times more likely (52%) than in subjects without PSN (16%; P = 0.001). In multivariate analysis, PSN was independently associated with PVD (odds ratio 2.31; P = 0.007), age (1.12; P = 0.008), male sex (2.01; P = 0.02), and HDL cholesterol (0.21; P < 0.05) and tended to be independently associated with IGF-1 binding protein (1.03; P = 0.05) but not with diabetes duration or A1C. CONCLUSIONS—In a representative population of type 2 diabetes, PSN is related to microvascular and macrovascular pathology. PSN is possibly affected by the IGF axis. PMID:19033412 Avci, Ahmet; Demir, Kenan; Kaya, Zeynettin; Marakoglu, Kamile; Ceylan, Esra; Ekmekci, Ahmet Hakan; Yilmaz, Ahmet; Demir, Aysegul; Altunkeser, Bulent Behlul We investigated the relationship between peripheral neuropathy and parameters of arterial stiffness and carotid intima media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM). The study included 161 patients (80 females and 81 males), 69 of whom had peripheral neuropathy. All patients underwent 24-h blood pressure monitoring, and arterial stiffness parameters were measured. The CIMT was measured using B-mode ultrasonography and patients also underwent transthoracic echocardiographic examination. Patients with peripheral neuropathy, compared with those without it, were older (54.68±8.35 years vs. 51.04±7.89 years; p=0.005) and had T2DM for longer periods (60 vs. 36 months; p=0.004). Glycated hemoglobin (HbA1c) values (8.55±1.85 mg/dL vs. 7.30±1.51 mg/dL; p<0.001), pulse wave velocity (PWV) (7.74±1.14 m/s vs. 7.15±1.10 m/s; p=0.001), CIMT (anterior 0.74±0.15 mm vs. 0.67±0.13 mm; p=0.01), and left ventricular mass (LVM) index (98.68±26.28 g/m2 vs. 89.71±19.70 g/m2; p=0.02) were all significantly increased in the group with peripheral neuropathy compared to the group without peripheral neuropathy. We determined that duration of diabetes, HbA1c, and LVM index were predictors of peripheral neuropathy. A significant relationship was found between diabetic neuropathy and increased PWV, a parameter of arterial stiffness, as well as CIMT, a marker of systemic atherosclerosis. Diabetic peripheral neuropathy may be a determinant of subclinical atherosclerosis in T2DM. Avci, Ahmet; Demir, Kenan; Kaya, Zeynettin; Marakoglu, Kamile; Ceylan, Esra; Ekmekci, Ahmet Hakan; Yilmaz, Ahmet; Demir, Aysegul; Altunkeser, Bulent Behlul Background We investigated the relationship between peripheral neuropathy and parameters of arterial stiffness and carotid intima media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM). Material/Methods The study included 161 patients (80 females and 81 males), 69 of whom had peripheral neuropathy. All patients underwent 24-h blood pressure monitoring, and arterial stiffness parameters were measured. The CIMT was measured using B-mode ultrasonography and patients also underwent transthoracic echocardiographic examination. Results Patients with peripheral neuropathy, compared with those without it, were older (54.68±8.35 years vs. 51.04±7.89 years; p=0.005) and had T2DM for longer periods (60 vs. 36 months; p=0.004). Glycated hemoglobin (HbA1c) values (8.55±1.85 mg/dL vs. 7.30±1.51 mg/dL; p<0.001), pulse wave velocity (PWV) (7.74±1.14 m/s vs. 7.15±1.10 m/s; p=0.001), CIMT (anterior 0.74±0.15 mm vs. 0.67±0.13 mm; p=0.01), and left ventricular mass (LVM) index (98.68±26.28 g/m2 vs. 89.71±19.70 g/m2; p=0.02) were all significantly increased in the group with peripheral neuropathy compared to the group without peripheral neuropathy. We determined that duration of diabetes, HbA1c, and LVM index were predictors of peripheral neuropathy. Conclusions A significant relationship was found between diabetic neuropathy and increased PWV, a parameter of arterial stiffness, as well as CIMT, a marker of systemic atherosclerosis. Diabetic peripheral neuropathy may be a determinant of subclinical atherosclerosis in T2DM. PMID:25351260 Safka Brozkova, Dana; Deconinck, Tine; Griffin, Laurie Beth; Ferbert, Andreas; Haberlova, Jana; Mazanec, Radim; Lassuthova, Petra; Roth, Christian; Pilunthanakul, Thanita; Rautenstrauss, Bernd; Janecke, Andreas R; Zavadakova, Petra; Chrast, Roman; Rivolta, Carlo; Zuchner, Stephan; Antonellis, Anthony; Beg, Asim A; De Jonghe, Peter; Senderek, Jan; Seeman, Pavel; Baets, Jonathan Inherited peripheral neuropathies are a genetically heterogeneous group of disorders characterized by distal muscle weakness and sensory loss. Mutations in genes encoding aminoacyl-tRNA synthetases have been implicated in peripheral neuropathies, suggesting that these tRNA charging enzymes are uniquely important for the peripheral nerve. Recently, a mutation in histidyl-tRNA synthetase (HARS) was identified in a single patient with a late-onset, sensory-predominant peripheral neuropathy; however, the genetic evidence was lacking, making the significance of the finding unclear. Here, we present clinical, genetic, and functional data that implicate HARS mutations in inherited peripheral neuropathies. The associated phenotypic spectrum is broad and encompasses axonal and demyelinating motor and sensory neuropathies, including four young patients presenting with pure motor axonal neuropathy. Genome-wide linkage studies in combination with whole-exome and conventional sequencing revealed four distinct and previously unreported heterozygous HARS mutations segregating with autosomal dominant peripheral neuropathy in four unrelated families (p.Thr132Ile, p.Pro134His, p.Asp175Glu and p.Asp364Tyr). All mutations cause a loss of function in yeast complementation assays, and p.Asp364Tyr is dominantly neurotoxic in a Caenorhabditis elegans model. This study demonstrates the role of HARS mutations in peripheral neuropathy and expands the genetic and clinical spectrum of aminoacyl-tRNA synthetase-related human disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected]. Dina, Olayinka A.; Khasar, Sachia G.; Alessandri-Haber, Nicole; Bogen, Oliver; Chen, Xiaojie; Green, Paul G.; Reichling, David B.; Messing, Robert O.; Levine, Jon D. Neurotoxic effects of catecholamine metabolites have been implicated in neurodegenerative diseases. Since some sensory neurons express tyrosine hydroxylase and monoamine oxidase (MAO) we investigated the potential contribution of catecholamine metabolites to neuropathic pain in a model of alcoholic neuropathy. The presence of catecholamines in sensory neurons is supported by capsaicin-stimulated epinephrine release, an effect enhanced in ethanol-fed rats. mRNA for enzymes in dorsal root ganglia involved in catecholamine uptake and metabolism, dopamine β-hydroxylase and MAO-A, were decreased by neonatal administration of capsaicin. Ethanol-induced hyperalgesia was attenuated by systemic and local peripheral administration of inhibitors of MAO-A, reduction of norepinephrine transporter (NET) in sensory neurons, and a NET inhibitor. Finally, intradermal injection of 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL), a neurotoxic MAO-A catecholamine metabolite, produced robust mechanical hyperalgesia. These observations suggest that catecholamines in nociceptors are metabolized to neurotoxic products by MAO-A, which can cause neuronal dysfunction underlying neuropathic pain. PMID:18783367 Dina, Olayinka A; Khasar, Sachia G; Alessandri-Haber, Nicole; Bogen, Oliver; Chen, Xiaojie; Green, Paul G; Reichling, David B; Messing, Robert O; Levine, Jon D The neurotoxic effects of catecholamine metabolites have been implicated in neurodegenerative diseases. As some sensory neurons express tyrosine hydroxylase and monoamine oxidase (MAO), we investigated the potential contribution of catecholamine metabolites to neuropathic pain in a model of alcoholic neuropathy. The presence of catecholamines in sensory neurons is supported by capsaicin-stimulated epinephrine release, an effect enhanced in ethanol-fed rats. mRNA for enzymes in dorsal root ganglia involved in catecholamine uptake and metabolism, dopamine beta-hydroxylase and MAO-A, were decreased by neonatal administration of capsaicin. Ethanol-induced hyperalgesia was attenuated by systemic and local peripheral administration of inhibitors of MAO-A, reduction of norepinephrine transporter (NET) in sensory neurons and a NET inhibitor. Finally, intradermal injection of 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL), a neurotoxic MAO-A catecholamine metabolite, produced robust mechanical hyperalgesia. These observations suggest that catecholamines in nociceptors are metabolized to neurotoxic products by MAO-A, which can cause neuronal dysfunction underlying neuropathic pain. Filipczak-Bryniarska, Iwona; Krzyzewski, Roger M; Kucharz, Jakub; Michalowska-Kaczmarczyk, Anna; Kleja, Justyna; Woron, Jarosław; Strzepek, Katarzyna; Kazior, Lucyna; Wordliczek, Jerzy; Grodzicki, Tomasz; Krzemieniecki, Krzysztof High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m(2). Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction. O'Donnell, Mark E; Badger, Stephen A; Sharif, Muhammed Anees; Makar, Ragai R; Young, Ian S; Lee, Bernard; Soong, Chee V Evidence from diabetic animal models suggests that cilostazol, a cyclic AMP phosphodiesterase inhibitor used in the treatment of claudication, is efficacious in the treatment of peripheral neuropathy, although this is unproven in humans. The main aim of this study was to assess the effects of cilostazol on neuropathic symptomatology in diabetic patients with peripheral arterial disease (PAD). Diabetic patients with PAD were prospectively recruited to a randomized double-blinded placebo-controlled trial. Baseline clinical data were recorded prior to trial commencement following medical optimization. Neurological assessment included the Toronto Clinical Neuropathy Scoring system (TCNS) and vibration perception thresholds (VPT) with a neurothesiometer at baseline, 6 weeks, and 24 weeks. Twenty-six patients were recruited from December 2004 to January 2006, which included 20 males. Baseline patient allocation to treatment arms was matched for age, sex, and medical comorbidities. There was no significant difference in neurological assessment between the treatment groups using the TCNS and VPT at 6 and 24 weeks. Despite extensive animal-based evidence that cilostazol attenuates neuropathic symptomatology, our results do not support this effect in human diabetic PAD patients. Park, Jae Sung; Kim, Sangri; Hoke, Ahmet Peripheral neuropathy is a major, dose-limiting complication of many chemotherapeutic agents. Currently there is no effective method to prevent development of chemotherapy-induced peripheral neuropathy (CIPN). Recent studies have shown that exercise can improve regeneration of peripheral nerves but its effect in preventing peripheral neuropathy is unknown. In this study, we examined the effect of a rigorous treadmill exercise program that was started 1 week before administration of paclitaxel and continued throughout the study in a mouse model of CIPN. We showed that exercise can partially abrogate features of axonal degeneration induced by paclitaxel including reduction in epidermal nerve fiber density in the plantar hind paw and thermal hypoalgesia. Furthermore, detyrosinated tubulin that is elevated in nerves treated with paclitaxel was normal in exercised animals. This study points to a relatively simple and potentially effective therapeutic option to reduce the neurotoxic effects of chemotherapy. © 2015 Peripheral Nerve Society. Visovsky, Constance; Meyer, Rachel R; Roller, Jeffre; Poppas, Megan Recently, chemotherapy-induced peripheral neuropathy has received a great deal of attention. However, the interaction of diabetic neuropathy with potentially neurotoxic chemotherapy is far less understood. The incidence of type II diabetes has risen exponentially in the past two decades. In concert with the rise in type II diabetes, the number of individuals with diabetes who need chemotherapy for cancer also is expected to increase. Diabetic neuropathy and the neurotoxic effects of chemotherapy have a significant potential to cause functional disability. Diabetics may be most at risk for the effects of neurotoxic agents on peripheral nerve functioning, in addition to the other effects induced by chemotherapeutic agents. The purpose of this article is to review the evaluation, management, and clinical implications of peripheral neuropathy in patients with cancer and diabetes. Jayakumar, Palanisamy; Shankar, Esaki Muthu; Karthikeyan, Murugesan; Ravikannan, Pandian The mechanisms behind certain co-morbid conditions associated with chronic HIV disease still remain elusive. HIV-associated peripheral neuropathy is one among those rarely studied manifestations in HIV-1 infection. Numerous underlying factors associated with peripheral neuropathy have been described in HIV disease. Herein, we hypothesized certain heretofore undescribed potential mechanisms that lead to HIV associated neuropathy. Being a multifactoral manifestation, HIV-associated neuropathy is presumed to have an association with physiological factors namely, adrenal inadequacy/steroid resistance and lipodystrophy-induced cushion-effect loss in peripheral nerves. Therefore, management of the adrenals with steroids at the time-point of high inflammatory burden thereby preventing lipodystrophy by selecting the optimum treatment regimen could markedly alleviate the severity of HIV-associated neuropathic manifestations. Copyright © 2011 Elsevier Ltd. All rights reserved. Kessler, Nathan J; Hong, Junggi The unsatisfactory results associated with conventional treatments for symptoms of diabetic peripheral neuropathy (DPN) demonstrate a need for research into alternative therapies. The purpose of this study was to determine the efficacy of whole body vibration therapy (WBV) as a treatment for pain associated with DPN. Participants (n = 8) with painful DPN received three treatment sessions per week for four weeks. Each session consisted of four bouts of 3 min of vibration (frequency 25 Hz, amplitude 5 mm). The primary outcome measures were changes in the visual analog pain scale (VAS) and changes in the neuropathic pain scale (NPS). WBV demonstrated a significant (p < 0.05) acute pain reduction in the VAS, and a significant chronic reduction in both the VAS and NPS scales. No side-effects were observed during this study. WBV appears to be an effective, non-invasive treatment for pain associated with DPN. Nudelman, Kelly N H; McDonald, Brenna C; Wang, Yang; Smith, Dori J; West, John D; O'Neill, Darren P; Zanville, Noah R; Champion, Victoria L; Schneider, Bryan P; Saykin, Andrew J To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment-related brain structural changes. Patients with breast cancer treated with (n = 24) or without (n = 23) chemotherapy underwent clinical examination and brain magnetic resonance imaging at the following three time points: before treatment (baseline), 1 month after treatment completion, and 1 year after the 1-month assessment. CIPN-sx were evaluated with the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity four-item sensory-specific scale. Perfusion and gray matter density were assessed using voxel-based pulsed arterial spin labeling and morphometric analyses and tested for association with CIPN-sx in the patients who received chemotherapy. Patients who received chemotherapy reported significantly increased CIPN-sx from baseline to 1 month, with partial recovery by 1 year (P < .001). CIPN-sx increase from baseline to 1 month was significantly greater for patients who received chemotherapy compared with those who did not (P = .001). At 1 month, neuroimaging showed that for the group that received chemotherapy, CIPN-sx were positively associated with cerebral perfusion in the right superior frontal gyrus and cingulate gyrus, regions associated with pain processing (P < .001). Longitudinal magnetic resonance imaging analysis in the group receiving chemotherapy indicated that CIPN-sx and associated perfusion changes from baseline to 1 month were also positively correlated with gray matter density change (P < .005). Peripheral neuropathy symptoms after systemic chemotherapy for breast cancer are associated with changes in cerebral perfusion and gray Nudelman, Kelly N.H.; McDonald, Brenna C.; Wang, Yang; Smith, Dori J.; West, John D.; O'Neill, Darren P.; Zanville, Noah R.; Champion, Victoria L.; Schneider, Bryan P. Purpose To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment–related brain structural changes. Methods Patients with breast cancer treated with (n = 24) or without (n = 23) chemotherapy underwent clinical examination and brain magnetic resonance imaging at the following three time points: before treatment (baseline), 1 month after treatment completion, and 1 year after the 1-month assessment. CIPN-sx were evaluated with the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity four-item sensory-specific scale. Perfusion and gray matter density were assessed using voxel-based pulsed arterial spin labeling and morphometric analyses and tested for association with CIPN-sx in the patients who received chemotherapy. Results Patients who received chemotherapy reported significantly increased CIPN-sx from baseline to 1 month, with partial recovery by 1 year (P < .001). CIPN-sx increase from baseline to 1 month was significantly greater for patients who received chemotherapy compared with those who did not (P = .001). At 1 month, neuroimaging showed that for the group that received chemotherapy, CIPN-sx were positively associated with cerebral perfusion in the right superior frontal gyrus and cingulate gyrus, regions associated with pain processing (P < .001). Longitudinal magnetic resonance imaging analysis in the group receiving chemotherapy indicated that CIPN-sx and associated perfusion changes from baseline to 1 month were also positively correlated with gray matter density change (P < .005). Conclusion Peripheral neuropathy symptoms after systemic chemotherapy for breast cancer are associated with Gupta, Harsh V; Lee, Ricky W; Raina, Sunil K; Behrle, Brian L; Hinduja, Archana; Mittal, Manoj K YouTube is an important resource for patients. No study has evaluated the information on peripheral neuropathy disseminated by YouTube videos. In this study, our aim was to perform a systematic review of information on YouTube regarding peripheral neuropathy. The Web site (www.youtube.com) was searched between September 19 and 21, 2014, for the terms "neuropathy," "peripheral neuropathy," "diabetic neuropathy," "neuropathy causes," and "neuropathy treatment." Two hundred videos met the inclusion criteria. Healthcare professionals accounted for almost half of the treatment videos (41 of 92; 44.6%), and most came from chiropractors (18 of 41; 43.9%). Alternative medicine was cited most frequently among the treatment discussions (54 of 145, 37.2%), followed by devices (38 of 145, 26.2%), and pharmacological treatments (23 of 145, 15.9%). Approximately half of the treatment options discussed in the videos were not evidence-based. Caution should be exercised when YouTube videos are used as a patient resource. © 2015 Wiley Periodicals, Inc. Prior, Robert; Van Helleputte, Lawrence; Benoy, Veronick; Van Den Bosch, Ludo Peripheral neuropathies are characterized by a progressive and length-dependent loss of peripheral nerve function. This can be caused either by genetic defects, classified as 'inherited peripheral neuropathies', or they can be acquired throughout life. In that case, the disease is caused by various insults such as toxins and mechanical injuries, or it can arise secondary to medical conditions such as metabolic disorders, nutritional deficiencies, inflammation and infections. Peripheral neuropathies are not only very heterogeneous in etiology, but also in their pathology and clinical presentation. A commonality amongst all peripheral neuropathies is that no pharmacological disease-modifying therapies currently exist that can reverse or cure these diseases. Moreover, the length-dependent nature of the disease, affecting the longest nerves at the most distal sites, suggests an important role for disturbances in axonal transport, directly or indirectly linked to alterations in the cytoskeleton. In this review, we will give a systematic overview of the main arguments for the involvement of axonal transport defects in both inherited and acquired peripheral neuropathies. In addition, we will discuss the possible therapeutic strategies that can potentially counteract these disturbances, as this particular pathway might be a promising strategy to find a cure. Since counteracting axonal transport defects could limit the axonal degeneration and could be a driving force for neuronal regeneration, the benefits might be twofold. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved. Brown, Steven J; Handsaker, Joseph C; Maganaris, Constantinos N; Bowling, Frank L; Boulton, Andrew J M; Reeves, Neil D To investigate lower limb biomechanical strategy during stair walking in patients with diabetes and patients with diabetic peripheral neuropathy, a population known to exhibit lower limb muscular weakness. The peak lower limb joint moments of twenty-two patients with diabetic peripheral neuropathy and thirty-nine patients with diabetes and no neuropathy were compared during ascent and descent of a staircase to thirty-two healthy controls. Fifty-nine of the ninety-four participants also performed assessment of their maximum isokinetic ankle and knee joint moment (muscle strength) to assess the level of peak joint moments during the stair task relative to their maximal joint moment-generating capabilities (operating strengths). Both patient groups ascended and descended stairs slower than controls (p<0.05). Peak joint moments in patients with diabetic peripheral neuropathy were lower (p<0.05) at the ankle and knee during stair ascent, and knee only during stair descent compared to controls. Ankle and knee muscle strength values were lower (p<0.05) in patients with diabetic peripheral neuropathy compared to controls, and lower at knee only in patients without neuropathy. Operating strengths were higher (p<0.05) at the ankle and knee in patients with neuropathy during stair descent compared to the controls, but not during stair ascent. Patients with diabetic peripheral neuropathy walk slower to alter gait strategy during stair walking and account for lower-limb muscular weakness, but still exhibit heightened operating strengths during stair descent, which may impact upon fatigue and the ability to recover a safe stance following postural instability. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved. Majithia, Neil; Temkin, Sarah M.; Ruddy, Kathryn J.; Beutler, Andreas S.; Hershman, Dawn L.; Loprinzi, Charles L. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and debilitating complications of cancer treatment. Due to a lack of effective management options for patients with CIPN, the National Cancer Institute (NCI) sponsored a series of trials aimed at both prevention and treatment. A total of 15 such studies were approved, evaluating use of various neuro-modulatory agents which have shown benefit in other neuropathic pain states. Aside from duloxetine, none of the pharmacologic methods demonstrated therapeutic benefit for patients with CIPN. Despite these disappointing results, the series of trials revealed important lessons that have informed subsequent work. Some examples of this include the use of patient-reported symptom metrics, the elimination of traditional—yet unsubstantiated—practice approaches, and the discovery of molecular genetic predictors of neuropathy. Current inquiry is being guided by the results from these large-scale trials, and as such, stands better chance of identifying durable solutions for this treatment-limiting toxicity. PMID:26686859 Tucker, K; Hedges, T R From late 1991 to mid-1993, cases of optic neuropathy of unknown etiology, which first appeared in unusual numbers in a western province of Cuba, spread and multiplied throughout the island. The dominant symptoms changed, becoming increasingly those of peripheral neuropathy. Incidence rates peaked in April 1993. An estimated 50,000 cases were reported. The majority were adult men and women (aged about 25-65), with comparatively few children or elderly people being affected. The cause has yet to be delineated. However, food shortages and radical changes in diet resulting from the longstanding US trade embargo and the recent loss of Eastern Europe as Cuba's trading partner have compromised nutritional status, especially B-vitamin sufficiency, and appear to be related to the neuropathic illnesses. In April 1993, the Cuban government began distributing vitamin supplements to every citizen. Causal hypotheses include tobacco-alcohol or "nutritional" amblyopia; cyanide toxicity from cassava; toxic legumes introduced as supplements to scarce flour; other toxins, for example pesticides, or a "blue mold" on tobacco; enterovirus; and a hereditary enzyme deficiency in affected persons. None of these factors appears to be present in all cases, but it is generally believed that an interaction of some toxin or toxins, in combination with nutritional deficiency, is likely to be the major cause. Nguyen, M T; Pham, I; Chemla, D; Valensi, P; Cosson, E To document the stroke volume to pulse pressure ratio (SV/PP, an index of total arterial compliance) and its correlates in patients with type 2 diabetes (T2DM) aged over 50 years whose peripheral neuropathy and silent myocardial ischemic (SMI) status were known. A total of 360 patients with T2DM aged ≥ 50 years, without cardiac history or symptom, left ventricular systolic dysfunction, dilatation and hypokinesia, were retrospectively enrolled. The SV/PP was calculated from echocardiographic left ventricular measurements and brachial blood pressure at rest. Peripheral neuropathy was defined as the presence of any two or more of the following: neuropathic symptoms, decreased distal sensation, or decreased or absent ankle reflexes. SMI was defined as an abnormal stress myocardial scintigraphy and/or stress echocardiography. A low SV/PP ratio (<0.53 ml/m²/mmHg, first tertile) was associated with age, creatinine clearance, 24 h urinary albumin excretion rate, peripheral neuropathy, hypertension, serum total cholesterol and triglycerides levels (p < 0.05-0.0001). In multivariate analysis, age (OR 1.1 [1.0-1.2], p < 0.01), triglycerides (OR 1.5 [1.2-2.0], p = 0.01) and peripheral neuropathy (OR 2.2 [1.2-3.9], p = 0.009) were independently associated with a low SV/PP. The patients with peripheral neuropathy had lower SV (p < 0.01) and higher PP (p < 0.05) than those without, and only lower SV after adjustment for age and nephropathy. Similar results were obtained in the patients with and without SMI. Peripheral neuropathy was independently associated with decreased SV/PP, mainly through decreased SV, in patients with T2DM over 50 years. Copyright © 2013 Elsevier B.V. All rights reserved. Hussain, Gauhar; Rizvi, S Aijaz Abbas; Singhal, Sangeeta; Zubair, Mohammad; Ahmad, Jamal To correlate serum levels of TGF-β1 with motor and sensory nerve conduction velocities in patients of type 2 diabetes mellitus The study was conducted in diagnosed type 2 diabetes mellitus patients which were divided in patients with clinically detectable peripheral neuropathy of shorter duration (n=37) and longer duration (n=27). They were compared with patients without clinical neuropathy (n=22). Clinical diagnosis was based on neuropathy symptom score (NSS) and Neuropathy disability score (NDS) for signs. Blood samples were collected for baseline investigations and estimation of serum TGF-β1. Nerve conduction velocity was measured in both upper and lower limbs. Median, Ulnar, Common Peroneal and Posterior Tibial nerves were selected for motor nerve conduction study and Median and Sural nerves were selected for sensory nerve conduction study In patients of type 2 diabetes mellitus with clinically detectable and serum TGF-β1 showed positive correlation with nerve conduction velocities High level of TGF-β1 in serum of T2DM patients with neuropathy show possible contribution in development of neuropathy. Due to its independent association this cytokine might be used as biomarker for diabetic peripheral neuropathy. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved. Leport, C; Chaunu, M P; Sicre, J; Brun-Vezinet, F; Hauw, J J; Vildé, J L An unexplained peripheral neuropathy was observed in five patients with positive serology for LAV/HTLV III. Three of them presented with polyneuropathy, one with chronic meningitis and oculomotor palsies, and one with a mononeuropathy. CSF was abnormal in 5/5, with elevated protein content (0.4-4 g/l) and abnormal cell count (29-65/mm3). Intrathecal production of LAV-specific IgG was demonstrated in 3/4 cases. Electromyographic examination showed reduced nerve conduction velocity in 4/5. Neuromuscular biopsy revealed microvasculitis with mononuclear cell infiltrates in 3/4 cases; characterization of these cells showed that they were predominantly non monoclonal T8 lymphocytes. Other symptoms of "AIDS-related complex" were present in all five patients. None had other causes of peripheral neuropathy. Thus, peripheral neuropathy can be the initial manifestation of LAV/HTLV III infection. Isolation of the virus from the nerve in one published case, and arguments for intrathecal synthesis of LAV-specific IgG suggest the direct role of this agent; however, the lymphocytic infiltration seen in three of our cases favours an indirect immune mechanism, as in other organs, such as lungs and lymph nodes. Fong, Jamie C.; Rojas, Julio C.; Bang, Jee; Legati, Andrea; Rankin, Katherine P.; Forner, Sven; Miller, Zachary A.; Karydas, Anna M.; Coppola, Giovanni; Grouse, Carrie K.; Ralph, Jeffrey; Miller, Bruce L.; Geschwind, Michael D. Patients with pathogenic truncating mutations in the prion gene (PRNP) usually present with prolonged disease courses with severe neurofibrillary tangle and cerebral amyloidosis pathology, but more atypical phenotypes also occur, including those with dysautonomia and peripheral neuropathy. We describe the neurological, cognitive, neuroimaging, and electrophysiological features of a 31-year-old man presenting with an orbitofrontal syndrome, gastrointestinal symptoms, and peripheral neuropathy associated with PRNP Q160X nonsense mutation, with symptom onset at age 27. The mutation was also detected in his asymptomatic father and a symptomatic paternal cousin; several members of prior generations died from early onset dementia. This is the first report of a family affected with the nonsense PRNP mutation Q160X displaying clear autosomal dominant disease in multiple family members and reduced penetrance. This case strengthens the evidence suggesting an association between PRNP truncating mutations and prion systemic amyloidosis. PRNP gene testing should be considered in any patient with atypical dementia, especially with early onset and neuropathy, even in the absence of a family history. PMID:27716661 Watanabe, Yuka; Odaka, Masaaki; Hirata, Koichi We report the case of a 28-year-old woman with Leber's hereditary optic neuropathy (LHON) associated with cerebellar ataxia, dilated cardiomyopathy and peripheral neuropathy. She had a mitochondrial DNA point mutation from guanine to adenine at nucleotide position 11778 and developed ataxic gait within 2 years after the onset of bilateral visual loss. A neurological examination detected horizontal nystagmus, bradylalia, and truncal and bilateral limb ataxia of the cerebellar type. She could walk, albeit unsteadily. There was no weakness in her arms and legs. Tendon jerks were diminished in both the upper arms. Bilateral knee and ankle jerks were absent, and the plantar responses were neutral. Paresthesia of the stocking type was present but no reduction of pinprick, position or vibration senses was detected in the paresthetic regions. Romberg's sign was negative. Brain MRI showed atrophic changes in both the cerebellar vermis and the hemispheres. Nerve conduction studies detected mildly decreased motor nerve conduction velocities in the median, ulnar and posterior tibial nerves. Ultrasound cardiography showed a dilated left ventricle. It was not possible to clarify the relationship between LHON and cerebellar atrophy, cardiomyopathy, and peripheral neuropathy. However, physicians, need to be aware that the patients may develop various neurological complications after the onset of optic neuropathy in LHON. Chhibber, Aparna; Mefford, Joel; Stahl, Eli A.; Pendergrass, Sarah A.; Baldwin, R. Michael; Owzar, Kouros; Li, Megan; Winer, Eric P.; Hudis, Clifford A.; Zembutsu, Hitoshi; Kubo, Michiaki; Nakamura, Yusuke; McLeod, Howard L.; Ratain, Mark J.; Shulman, Lawrence N.; Ritchie, Marylyn D.; Plenge, Robert M.; Witte, John S.; Kroetz, Deanna L. Peripheral neuropathy is a common dose-limiting toxicity for patients treated with paclitaxel. For most individuals there are no known risk factors that predispose patients to the adverse event, and pathogenesis for paclitaxel-induced peripheral neuropathy is unknown. Determining whether there is a heritable component to paclitaxel induced peripheral neuropathy would be valuable in guiding clinical decisions and may provide insight into treatment of and mechanisms for the toxicity. Using genotype and patient information from the paclitaxel arm of CALGB 40101 (Alliance), a phase III clinical trial evaluating adjuvant therapies for breast cancer in women, we estimated the variance in maximum grade and dose at first instance of sensory peripheral neuropathy. Our results suggest that paclitaxel-induced neuropathy has a heritable component, driven in part by genes involved in axon outgrowth. Disruption of axon outgrowth may be one of the mechanisms by which paclitaxel treatment results in sensory peripheral neuropathy in susceptible patients. PMID:24513692 Chhibber, A; Mefford, J; Stahl, E A; Pendergrass, S A; Baldwin, R M; Owzar, K; Li, M; Winer, E P; Hudis, C A; Zembutsu, H; Kubo, M; Nakamura, Y; McLeod, H L; Ratain, M J; Shulman, L N; Ritchie, M D; Plenge, R M; Witte, J S; Kroetz, D L Peripheral neuropathy is a common dose-limiting toxicity for patients treated with paclitaxel. For most individuals, there are no known risk factors that predispose patients to the adverse event, and pathogenesis for paclitaxel-induced peripheral neuropathy is unknown. Determining whether there is a heritable component to paclitaxel-induced peripheral neuropathy would be valuable in guiding clinical decisions and may provide insight into treatment of and mechanisms for the toxicity. Using genotype and patient information from the paclitaxel arm of CALGB 40101 (Alliance), a phase III clinical trial evaluating adjuvant therapies for breast cancer in women, we estimated the variance in maximum grade and dose at first instance of sensory peripheral neuropathy. Our results suggest that paclitaxel-induced neuropathy has a heritable component, driven in part by genes involved in axon outgrowth. Disruption of axon outgrowth may be one of the mechanisms by which paclitaxel treatment results in sensory peripheral neuropathy in susceptible patients. Kerckhove, Nicolas; Collin, Aurore; Condé, Sakahlé; Chaleteix, Carine; Pezet, Denis; Balayssac, David Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors. Pathophysiological mechanisms and risk factors are also presented. Neurotoxic mechanisms leading to CIPNs are not yet fully understood but involve neuronopathy and/or axonopathy, mainly associated with DNA damage, oxidative stress, mitochondria toxicity, and ion channel remodeling in the neurons of the peripheral nervous system. Classical symptoms of CIPNs are peripheral neuropathy with a “stocking and glove” distribution characterized by sensory loss, paresthesia, dysesthesia and numbness, sometimes associated with neuropathic pain in the most serious cases. Several risk factors can promote CIPN as a function of the anticancer drug considered, such as cumulative dose, treatment duration, history of neuropathy, combination of therapies and genetic polymorphisms. CIPNs are frequent in cancer patients with an overall incidence of approximately 38% (possibly up to 90% of patients treated with oxaliplatin). Finally, the long-term reversibility of these CIPNs remain questionable, notably in the case of platinum-based anticancer drugs and taxanes, for which CIPN may last several years after the end of anticancer chemotherapies. These long-term effects are associated with comorbidities such as depression, insomnia, falls and decreases of health-related quality of life in cancer patients and survivors. However, it is noteworthy that these long-term effects remain poorly studied, and only limited data are available such as in Kerckhove, Nicolas; Collin, Aurore; Condé, Sakahlé; Chaleteix, Carine; Pezet, Denis; Balayssac, David Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors. Pathophysiological mechanisms and risk factors are also presented. Neurotoxic mechanisms leading to CIPNs are not yet fully understood but involve neuronopathy and/or axonopathy, mainly associated with DNA damage, oxidative stress, mitochondria toxicity, and ion channel remodeling in the neurons of the peripheral nervous system. Classical symptoms of CIPNs are peripheral neuropathy with a "stocking and glove" distribution characterized by sensory loss, paresthesia, dysesthesia and numbness, sometimes associated with neuropathic pain in the most serious cases. Several risk factors can promote CIPN as a function of the anticancer drug considered, such as cumulative dose, treatment duration, history of neuropathy, combination of therapies and genetic polymorphisms. CIPNs are frequent in cancer patients with an overall incidence of approximately 38% (possibly up to 90% of patients treated with oxaliplatin). Finally, the long-term reversibility of these CIPNs remain questionable, notably in the case of platinum-based anticancer drugs and taxanes, for which CIPN may last several years after the end of anticancer chemotherapies. These long-term effects are associated with comorbidities such as depression, insomnia, falls and decreases of health-related quality of life in cancer patients and survivors. However, it is noteworthy that these long-term effects remain poorly studied, and only limited data are available such as in the Rajaobelina, K; Farges, B; Nov, S; Maury, E; Cephise-Velayoudom, F L; Gin, H; Helmer, C; Rigalleau, V Advanced glycation end products (AGEs) are involved in diabetes complications. We aimed to investigate whether the accumulation of AGEs measured by skin autofluorescence (sAF) was associated with signs of diabetic peripheral neuropathy and to sensitivity, pain, motor and autonomic function 4 years later in patients with type 1 diabetes. At baseline, 188 patients (age 51 years, diabetes duration 22 years) underwent skin autofluorescence measurement using the AGE Reader. Four years later, signs of diabetic peripheral neuropathy were defined as the presence of neuropathic pain and/or feet sensory loss or foot ulceration. Neurological tests were systematically performed: vibration perception threshold by neuroesthesiometry, neuropathic pain by the Douleur Neuropathique en 4 Questions score, muscle strength by dynamometry and electrochemical skin conductance. Multivariate analyses were adjusted by age, sex, height, body mass index, tobacco, HbA1c , diabetes duration, estimated glomerular filtration rate and albumin excretion rate. At the 4-year follow-up, 13.8% of patients had signs of diabetic peripheral neuropathy. The baseline sAF was higher in those with signs of diabetic peripheral neuropathy (2.5 ± 0.7 vs 2.1 ± 0.5 arbitrary units (AU), p < 0.0005). In the multivariate analysis, a 1 SD higher skin autofluorescence at baseline was associated with an increased risk of signs of neuropathy (OR = 2.68, p = 0.01). All of the neurological tests were significantly altered in the highest quartile of the baseline sAF (>2.4 AU) compared with the lowest quartiles after multivariate adjustment. This non-invasive measurement of skin autofluorescence may have a value for diabetic peripheral neuropathy in type 1 diabetes and a potential clinical utility for detection of diabetic peripheral neuropathy. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd. Pitceathly, Robert D. S.; Blake, Julian C.; Woodward, Catherine E.; Zapater, Pedro; Fratter, Carl; Mudanohwo, Ese E.; Plant, Gordon T.; Houlden, Henry; Sweeney, Mary G.; Hanna, Michael G.; Reilly, Mary M. Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P < 0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P = 0.002; odds ratio 8.43, 95% confidence Horga, Alejandro; Pitceathly, Robert D S; Blake, Julian C; Woodward, Catherine E; Zapater, Pedro; Fratter, Carl; Mudanohwo, Ese E; Plant, Gordon T; Houlden, Henry; Sweeney, Mary G; Hanna, Michael G; Reilly, Mary M Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P<0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P=0.002; odds ratio 8.43, 95% confidence interval 2 Reeves, Brandi N.; Dakhil, Shaker R.; Sloan, Jeff A.; Wolf, Sherry L.; Burger, Kelli N.; Kamal, Arif; Le-Lindqwister, Nguyet A.; Soori, Gamini S.; Jaslowski, Anthony J.; Kelaghan, Joseph; Novotny, Paul J.; Lachance, Daniel H.; Loprinzi, Charles L. Background Paclitaxel causes an acute pain syndrome (P-APS), occurring within days after each dose and usually abating within days. Paclitaxel also causes a more classic peripheral neuropathy, which steadily increases in severity with increasing paclitaxel total doses. Little detail is available regarding the natural history of these two syndromes, or any relationship between them, although a recent publication does provide natural history data about weekly paclitaxel, supporting an association between the severity of P-APS and eventual peripheral neuropathy symptoms. Methods Patients entering this study were about to receive paclitaxel and carboplatin every 3 weeks. Daily questionnaires were completed for the first week after every chemotherapy dose and EORTC QLQ-CIPN 20 instruments were completed weekly. Results The P-APS severity peaked on day 4 after the initial chemotherapy dose, with 12%, 29%, 23%, and 36% of patients having maximal pain scores of 0, 1–4, 5–6, or 7–10 during the first week after the first dose of therapy, respectively. Patients with P-APS scores of 0–4 with the first dose of chemotherapy had less eventual sensory neuropathy than did patients with P-APS scores of 5–10 (p=0.001). With regard to the more peripheral neuropathy, sensory neuropathy was more problematic than was either motor or autonomic neuropathy. Numbness and tingling were more common components of the sensory neuropathy, than was pain. Conclusions Patients with worse P-APS severities appear to have more eventual chemotherapy induced peripheral neuropathy. This provides support for the concept that the P-APS is a form of nerve pathology. PMID:22415454 Krishnan, Pramod; Mahadevan, Anita; Bindu, Parayil Sankaran; Chickabasaviah, Yasha T; Taly, Arun B There are only a few studies describing the etiologic spectrum of biopsy-proven peripheral neuropathies in children. This study reviewed the clinical, electrophysiological, and pathologic profile of 239 children (≤18 years of age) who have undergone nerve biopsy in a tertiary care centre for neurologic disorders and analyzed the etiologic spectrum and utility of nerve biopsy. The clinical profile, neuropathologic findings, and other investigations were combined to infer the final diagnosis. Neuropathy was detected in 199 biopsies; axonal pathology in 43%; demyelination in 41%; mixed pattern in 8%; and nonspecific findings in 8%. The major diagnostic categories included hereditary neuropathies (48%), heredodegenerative and metabolic disorders (27%), and inflammatory neuropathies (12%). Nerve biopsy proved most helpful in diagnosis of demyelinating and inflammatory neuropathies, reiterating its usefulness in specific situations. © The Author(s) 2014. Ogbera, Anthonia O; Adeleye, Olufunmilayo; Solagberu, Babatunde; Azenabor, Alfred Identifying the risk factors for diabetes mellitus related foot ulceration would save more limbs from amputation. This report focuses on the determining the burden of peripheral arterial disease and neuropathy in persons with diabetes mellitus (DM). This is a descriptive study carried out in the Diabetic Clinic of the Lagos State University Teaching Hospital in patients with DM who had no past/present history of foot ulceration. Biothesiometry was employed and ankle brachial pressure indices were measured to evaluate for neuropathy and peripheral arterial disease (PAD) respectively. A total of 225 persons living with DM who met inclusion criteria were recruited consecutively over a 3 months period. Age range was 28-87 years with the mean [61.4 (10.8)] and median (63) years respectively. Patients symptomatic for neuropathy and PAD were 37 and 40 % respectively of the study population. An older age of >60 years and poor glycaemic control were potential predictors of neuropathy. Neuropathy and PAD occurred commonly in the seventh decade of life. Given the fairly high proportions of neuropathy and PAD in our patients with DM, we recommend that they be routinely examined in persons with DM. Kawata, Daisuke; Wu, Zetang Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating complication associated with drug treatment of cancer. For which there are no effective strategies of prevention or treatment. In this study we examined the effect of intermittent expression of neurotophin-3 (NT-3) or interleukin 10 (IL-10) from replication-defective herpes simplex virus (HSV)-based regulatable vectors delivered by subcutaneous inoculation to dorsal root ganglion (DRG) on the development of paclitaxel-induced peripheral neuropathy. We constructed two different tetracycline (tet)-on based regulatable HSV vectors, one expressing NT-3 and the other expressing IL-10, in which the transactivator expression in the tet-on system was under the control of HSV latency associated promoter 2 (LAP-2) and expression of the transgene was controlled by doxycycline (DOX). We examined the therapeutic effect of intermittent expression of the transgene in animals with paclitaxel-induced peripheral neuropathy modeled by intraperitoneal injection of paclitaxel (16 mg/kg) once a week for 5 weeks. Intermittent expression of either NT-3 or IL-10 3 days before and 1 day after paclitaxel administration protected animals against paclitaxel-induced peripheral neuropathy over the course of 5 weeks. These results suggest the potential of regulatable vectors for prevention of chemotherapy-induced peripheral neuropathy. Kawata, Daisuke; Wu, Zetang Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating complication associated with drug treatment of cancer for which there are no effective strategies of prevention or treatment. In this study, we examined the effect of intermittent expression of neurotophin-3 (NT-3) or interleukin-10 (IL-10) from replication-defective herpes simplex virus (HSV)-based regulatable vectors delivered by subcutaneous inoculation to the dorsal root ganglion (DRG) on the development of paclitaxel-induced peripheral neuropathy. We constructed two different tetracycline (tet)-on-based regulatable HSV vectors, one expressing NT-3 and the other expressing IL-10, in which the transactivator expression in the tet-on system was under the control of HSV latency-associated promoter 2 (LAP-2), and expression of the transgene was controlled by doxycycline (DOX). We examined the therapeutic effect of intermittent expression of the transgene in animals with paclitaxel-induced peripheral neuropathy modeled by intraperitoneal injection of paclitaxel (16 mg/kg) once a week for 5 weeks. Intermittent expression of either NT-3 or IL-10 3 days before and 1 day after paclitaxel administration protected animals against paclitaxel-induced peripheral neuropathy over the course of 5 weeks. These results suggest the potential of regulatable vectors for prevention of chemotherapy-induced peripheral neuropathy. Fardell, Joanna E; Vardy, Janette; Monds, Lauren A; Johnston, Ian N Chemotherapy treatment is associated with cognitive dysfunction in cancer survivors after treatment completion. The duration of these impairments is unclear. Therefore this paper aims to evaluate the lasting impact of varying doses of the chemotherapy oxaliplatin (OX) on cognition and peripheral neuropathy. In Experiment 1 rats were treated once a week for 3 weeks with either physiological saline (control) or 6 mg/kg OX i.p. and were assessed for peripheral neuropathy, using von Frey filaments, and cognitive function, using novel object and location recognition, up to 2 weeks after treatment completion. For Experiment 2 rats received 3 weekly i.p. injections of either physiological saline (control), 0.6 mg/kg, 2mg/kg or 6 mg/kg OX and assessed for peripheral neuropathy and cognitive function up to 11 months after treatment completion. Systemic OX treatment induced lasting effects on cognitive function at 11 months after treatment, and peripheral neuropathy at 1 month after treatment and these were dose dependent; higher doses of OX resulted in worse cognitive outcomes and more severe peripheral neuropathy. Copyright © 2015. Published by Elsevier B.V. Melli, Giorgia; Höke, Ahmet Background Peripheral neuropathies affect many people worldwide and are caused by or associated with a wide range of conditions, both genetic and acquired. Current therapies are directed at symptomatic control because no effective regenerative treatment exists. Primary challenge is that mechanisms that lead to distal axonal degeneration, a common feature of all peripheral neuropathies, are largely unknown. Objective/Methods To address the role and specific characteristics of dorsal root ganglia (DRG) derived sensory neuron culture system as a useful model in evaluating the pathogenic mechanisms of peripheral neuropathies and examination and validation of potential therapeutic compounds. A thorough review of the recent literature was completed and select examples of the use of DRG neurons in different peripheral neuropathy models were chosen to highlight the utility of these cultures. Conclusion Many useful models of different peripheral neuropathies have been developed using DRG neuronal culture and potential therapeutic targets have been examined, but so far none of the potential therapeutic compounds have succeeded in clinical trials. In recent years, focus has changed to evaluation of axon degeneration as the primary outcome measure advocating a drug development strategy starting with phenotypic drug screening, followed by validation in primary complex co-cultures and animal models. PMID:20657751 Smith, Thomas J; Auwaerter, Paul; Knowlton, Amy; Saylor, Deanna; McArthur, Justin Peripheral neuropathy is one of the most common neurological complications of HIV infection with a 30-60% lifetime prevalence. Newer HIV drugs cause less peripheral neuropathy, but patients are now living long enough to develop concomitant diabetes-related, vascular-related, and chemotherapy-related neuropathy so it continues as a major debilitating issue. Recent national CDC guidelines have stressed the importance of non-opioid therapies, especially in this population that may have had drug abuse problems. We treated a 52-year-old man who had severe disabling classic peripheral neuropathy since 1998 with Scrambler Therapy (Calmare), an FDA-cleared peripheral non-invasive neuromodulation device. His pain rapidly improved, as did his motor and sensory function, with just four 45-min treatments, and he was able to come off opioids for the first time in years. When his pain returned six months later, only two treatments were needed to resolve it. This represents the first published use of this novel, inexpensive, and non-invasive pain modality in HIV peripheral neuropathy, and should engender further trials. Phillips, Tudor J C; Brown, Matthew; Ramirez, Juan D; Perkins, James; Woldeamanuel, Yohannes W; Williams, Amanda C de C; Orengo, Christine; Bennett, David L H; Bodi, Istvan; Cox, Sarah; Maier, Christoph; Krumova, Elena K; Rice, Andrew S C HIV-associated sensory neuropathy (HIV-SN) is a frequent complication of HIV infection and a major source of morbidity. A cross-sectional deep profiling study examining HIV-SN was conducted in people living with HIV in a high resource setting using a battery of measures which included the following: parameters of pain and sensory symptoms (7day pain diary, Neuropathic Pain Symptom Inventory [NPSI] and Brief Pain Inventory [BPI]), sensory innervation (structured neurological examination, quantitative sensory testing [QST] and intraepidermal nerve fibre density [IENFD]), psychological state (Pain Anxiety Symptoms Scale-20 [PASS-20], Depression Anxiety and Positive Outlook Scale [DAPOS], and Pain Catastrophizing Scale [PCS], insomnia (Insomnia Severity Index [ISI]), and quality of life (Short Form (36) Health Survey [SF-36]). The diagnostic utility of the Brief Peripheral Neuropathy Screen (BPNS), Utah Early Neuropathy Scale (UENS), and Toronto Clinical Scoring System (TCSS) were evaluated. Thirty-six healthy volunteers and 66 HIV infected participants were recruited. A novel triumvirate case definition for HIV-SN was used that required 2 out of 3 of the following: 2 or more abnormal QST findings, reduced IENFD, and signs of a peripheral neuropathy on a structured neurological examination. Of those with HIV, 42% fulfilled the case definition for HIV-SN (n=28), of whom 75% (n=21) reported pain. The most frequent QST abnormalities in HIV-SN were loss of function in mechanical and vibration detection. Structured clinical examination was superior to QST or IENFD in HIV-SN diagnosis. HIV-SN participants had higher plasma triglyceride, concentrations depression, anxiety and catastrophizing scores, and prevalence of insomnia than HIV participants without HIV-SN. Phillips, Tudor J.C.; Brown, Matthew; Ramirez, Juan D.; Perkins, James; Woldeamanuel, Yohannes W.; Williams, Amanda C. de C.; Orengo, Christine; Bennett, David L.H.; Bodi, Istvan; Cox, Sarah; Maier, Christoph; Krumova, Elena K.; Rice, Andrew S.C. HIV-associated sensory neuropathy (HIV-SN) is a frequent complication of HIV infection and a major source of morbidity. A cross-sectional deep profiling study examining HIV-SN was conducted in people living with HIV in a high resource setting using a battery of measures which included the following: parameters of pain and sensory symptoms (7 day pain diary, Neuropathic Pain Symptom Inventory [NPSI] and Brief Pain Inventory [BPI]), sensory innervation (structured neurological examination, quantitative sensory testing [QST] and intraepidermal nerve fibre density [IENFD]), psychological state (Pain Anxiety Symptoms Scale-20 [PASS-20], Depression Anxiety and Positive Outlook Scale [DAPOS], and Pain Catastrophizing Scale [PCS], insomnia (Insomnia Severity Index [ISI]), and quality of life (Short Form (36) Health Survey [SF-36]). The diagnostic utility of the Brief Peripheral Neuropathy Screen (BPNS), Utah Early Neuropathy Scale (UENS), and Toronto Clinical Scoring System (TCSS) were evaluated. Thirty-six healthy volunteers and 66 HIV infected participants were recruited. A novel triumvirate case definition for HIV-SN was used that required 2 out of 3 of the following: 2 or more abnormal QST findings, reduced IENFD, and signs of a peripheral neuropathy on a structured neurological examination. Of those with HIV, 42% fulfilled the case definition for HIV-SN (n = 28), of whom 75% (n = 21) reported pain. The most frequent QST abnormalities in HIV-SN were loss of function in mechanical and vibration detection. Structured clinical examination was superior to QST or IENFD in HIV-SN diagnosis. HIV-SN participants had higher plasma triglyceride, concentrations depression, anxiety and catastrophizing scores, and prevalence of insomnia than HIV participants without HIV-SN. PMID:24973717 Abd-Elsayed, Alaa; Schiavoni, Nick; Sachdeva, Harsh Peripheral neuropathy is a common cause of pain, and it is increasing in prevalence. Peripheral neuropathic pain is very hard to treat and can be resistant to multiple pain management modalities. Our series aimed at testing the efficacy of spinal cord stimulators (SCSs) in treating resistant painful peripheral neuropathy. Case 1: A 79-year-old man presented to our clinic with long-standing history of painful peripheral diabetic neuropathy resistant to conservative management. After failure of all possible modalities, we offered the patient an SCS trial that was very successful, and we proceeded with the permanent implant that continued to help with his pain and allowed the patient to wean down his medications. Case 2: A 60-year-old man presented with chronic peripheral neuropathy secondary to HIV, patient failed all conservative and procedural management. Patient then had an SCS trial that relieved his pain significantly. Unfortunately, we did not proceed with the implant due to deterioration of the patient general health. Case 3: A 39-year-old woman presented with painful peripheral neuropathy secondary to chemotherapy for breast cancer. After failure of medication management and procedures, patient had a SCS trial that improved her pain and we then proceeded with performing the permanent implant that controlled her pain. We presented 3 cases with chronic painful peripheral neuropathy secondary to HIV, diabetes mellitus, and chemotherapy that was resistant to conservative pain management and procedures that was successfully treated with neurostimulation. Copyright © 2016 Elsevier Inc. All rights reserved. Shaikh, Asma; Bentley, Alison; Kamerman, Peter R The terminology used to describe neuropathic pain appears to be conserved across languages, which facilitates the translation of validated neuropathic pain screening tools into other languages. However, this assumption has not been assessed in an African language. Therefore we investigated the terminology used by 54 patients whose native language was isiZulu, a major Bantu language of Africa, when describing their symptomatic HIV-associated sensory neuropathy. Also, because English is a commonly spoken second-language in the region, we assessed these patients' knowledge and understanding of 21 English terms commonly used to describe neuropathic pain. English translations of the most commonly used isiZulu symptom descriptors included: "hot/burning" (50%), "cramping" (35%), "painful/sore/aching" (32%), "itching" (22%), "numb" (22%), "cold/freezing" (17%), and "stabbing/pricking/pins-and-needles" (13%). Thus, the isiZulu terminology to describe neuropathic pain was very similar to that used in non-African languages. However, knowledge and understanding of English neuropathic pain descriptors by these non-native English speakers was highly variable. For example, knowledge of English terms ranged from >98% ("hot", "cold/freezing", "cramping") to <25% ("pricking", "radiating", "throbbing"), and true understanding of English terms ranged from >90% ("hot", "burning", "cramping") to <35% ("tingling", "jumping", "shooting", "radiating"). In conclusion, we show significant similarity in the terms used to describe neuropathic pain in isiZulu compared to non-African languages, thus indicating that translation of existing neuropathic pain screening tools into this, and possibly other Bantu languages, is a viable option. However, the usefulness of English-language screening tools in this non-native English speaking population may be limited. Anandacoomaraswamy, Dharshan; Ullal, Jagdeesh; Vinik, Aaron I This is a case of a 70-year-old man with severe peripheral neuropathy, type 2 diabetes and progressively worsening cerebellar ataxia. He was found to have circulating antigliadin and antireticulin antibodies compatible with celiac disease in the absence of intestinal pathology. The peripheral neuropathy improved with a gluten-free diet, antioxidants and intravenous immunoglobulin, whereas the ataxia did not. This case illustrates the need to test for celiac disease in patients with idiopathic ataxia and peripheral neuropathy and the need for alternative therapies for ataxia. PMID:21197340 Anandacoomaraswamy, Dharshan; Ullal, Jagdeesh; Vinik, Aaron I This is a case of a 70-year-old man with severe peripheral neuropathy, type 2 diabetes and progressively worsening cerebellar ataxia. He was found to have circulating antigliadin and antireticulin antibodies compatible with celiac disease in the absence of intestinal pathology. The peripheral neuropathy improved with a gluten-free diet, antioxidants and intravenous immunoglobulin, whereas the ataxia did not. This case illustrates the need to test for celiac disease in patients with idiopathic ataxia and peripheral neuropathy and the need for alternative therapies for ataxia. Börü, Ulkü Türk; Alp, Recep; Sargin, Haluk; Koçer, Abdulkadir; Sargin, Mehmet; Lüleci, Arda; Yayla, Ali The aim of this study was to determine the prevalence and risk factors for neuropathy in type 2 diabetic patients attending a major Turkish diabetes center. Eight hundred and sixty-six consecutive type 2 diabetic patients were included in the study. A single observer performed biothesiometry studies on these patients. The presence of diabetic neuropathy was investigated using neurological symptom scale (NSS) and neurological disability score (NDS) performed. Neuropathy was determined with standardized neurological examinations and defined as the presence of abnormal NSS and NDS together with abnormal sensory or motor signs and symptoms as well as decreased great toe vibration perception. Overall, 60% (n = 520) of the patients were diagnosed as having neuropathy. The prevalence of neuropathy increased with age (p < 0.001) and duration of diabetes (p < 0.001). Multiple logistic regression analysis revealed the duration of diabetes (p < 0.001) and HbA1c levels (p < 0.001) as the risk factors for neuropathy. The overall prevalence of neuropathy in Turkish type 2 diabetic population was 60%. Age, duration of diabetes, and poor glycemic control were considered to be the risk factors for neuropathy. Kobayashi, Yu; Tohyama, Jun; Akiyama, Tomoyuki; Magara, Shinichi; Kawashima, Hideshi; Akasaka, Noriyuki; Nakashima, Mitsuko; Saitsu, Hirotomo; Matsumoto, Naomichi Cerebral folate deficiency due to folate receptor 1 gene (FOLR1) mutations is an autosomal recessive disorder resulting from a brain-specific folate transport defect. It is characterized by late infantile onset, severe psychomotor regression, epilepsy, and leukodystrophy. We describe a consanguineous girl exhibiting severe developmental regression, intractable epilepsy, polyneuropathy, and profound hypomyelination with cortical involvement. Magnetic resonance imaging showed cortical disturbances in addition to profound hypomyelination and cerebellar atrophy. Nerve conduction studies revealed both axonal degeneration and demyelinating features. A diagnosis of cerebral folate deficiency was confirmed by a homozygous c.466T>G (p.W156G) mutation in FOLR1, coupled with extremely low cerebrospinal fluid levels of 5-methyltetrahydrofolate. Her symptoms, neuroradiological findings, and polyneuropathy were alleviated by oral folinic acid treatment in conjunction with intravenous and intramuscular administration therapy. Our patient shows that folinic acid therapy can ameliorate the clinical symptoms, white matter disturbances, cortical insults, and peripheral neuropathy of cerebral folate deficiency caused by FOLR1 mutation. It is important to recognize these clinical symptoms and make a precise diagnosis early on, because cerebral folate deficiency is treatable. Knoerl, Robert; Dudley, William N; Smith, Gloria; Bridges, Celia; Kanzawa-Lee, Grace; Lavoie Smith, Ellen M Because numerous barriers hinder the assessment and management of chemotherapy-induced peripheral neuropathy in clinical practice, the Carevive Care Planning System, a novel Web-based platform, was developed to address these barriers. It provides patients an opportunity to report their symptoms before their clinic visit and generates customizable care plans composed of evidence-based management strategies. The purpose of this study was to evaluate patient and provider perspectives of feasibility, usability, acceptability, and satisfaction with the Carevive platform. We used a single-arm, pretest/posttest, prospective design and recruited 25 women with breast cancer who were receiving neurotoxic chemotherapy and six advanced practice providers from an academic hospital. At three consecutive clinical visits, patients reported their neuropathy symptoms on a tablet via the Carevive system. The Diffusion of Innovations Theory served as an overarching evaluation framework. The Carevive platform was feasible to use. However, patients had higher ratings of usability, acceptability, and satisfaction with the platform than did the providers, who disliked the amount of time required to use the platform and had difficulty logging into Carevive. If issues regarding provider dissatisfaction can be addressed, the Carevive platform may aid in the screening of neuropathy symptoms and facilitate the use of evidence-based management strategies. Desai, Bansri; Freeman, Erin; Huang, Ellen; Hung, Anna; Knapp, Edward; Breunig, Ian M; McPherson, Mary L; Shaya, Fadia T Painful diabetic peripheral neuropathy is difficult to treat, partially because the underlying mechanism of pain is not fully understood. Various treatment guidelines recommend first-line agents, such as α2-δ ligands, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants but combination therapy of alternative agents including opiates is often warranted. Tapentadol extended-release has a novel dual mechanism of action; it is both a mu-opioid receptor agonist and a norephinephrine reuptake inhibitor. It has been in the spotlight since it was FDA-approved specifically for the treatment of painful diabetic peripheral neuropathy in 2012. Previous reviews of tapentadol have focused on chronic pain. The purpose of this review article is to assess the efficacy and safety of tapentadol extended-release in adult populations with painful diabetic peripheral neuropathy and provide guidance for formulary decisions. Otake, Akiko; Yoshino, Kiyoshi; Ueda, Yutaka; Sawada, Kenjiro; Mabuchi, Seiji; Kimura, Toshihiro; Kobayashi, Eiji; Isobe, Aki; Egawa-Takata, Tomomi; Matsuzaki, Shinya; Fujita, Masami; Kimura, Tadashi The present study aimed at evaluating the usefulness and adverse effects of duloxetine treatment for paclitaxel-induced peripheral neuropathy in gynecological cancer patients. Medical records of gynecological cancer patients treated with duloxetine were retrospectively studied to evaluate the drug's efficacy for paclitaxel-induced peripheral neuropathy. RESULTS from 25 patients showed that an improved response was observed in 14 (56%). By univariate and multivariate analysis, the patient's age, tumor origin, regimen of chemotherapy, accumulated doses of paclitaxel or carboplatin, previous medication, maintenance dosage and timing of treatment with duloxetine were found not to be associated with the effectiveness of duloxetine treatment. Adverse effects with duloxetine were mild and well-tolerated. As an option, duloxetine can be effectively used for paclitaxel-induced peripheral neuropathy in patients with gynecological cancers, irrespective of patients' age, origin of the tumor, regimen of chemotherapy, or previous medication. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. Han, Li-Ping; Yu, De-Min; Xie, Yun To investigate the effects of lisinopril, an angiotensin-converting enzyme inhibitor, on diabetic peripheral neuropathy (DNP). Twenty-five Wistar rats underwent intravenous injection of streptozocin to establish diabetes models and 10 rats were injected with sodium citrate solution as normal controls. The diabetic rats were randomly divided into 2 groups: lisinopril group treated with gastric perfusion of lisinopril daily for 8 weeks, and diabetic control group. The diabetic controls and normal controls were treated with gastric perfusion of water. Sciatic nerve electrode penetration method was used to measure the motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV). Light and heat pain measuring apparatus was used to measure the pain threshold. Then the sciatic nerves were isolated. Electron microscopy was used to observe the ultra-structure. The contents of superoxide dismutase (SOD) and malonyldialdehyde (MDA), and Na(+)K(+)-ATPase activity were detected by chemical colorimetry. Immunohistochemistry was used to detect the CD34 in the sciatic nerve. The capillary density of sciatic nerve was calculated. The MNCV and SNCV levels of the lisinopril group were both lower than those of the 2 control groups (all P < 0.01). The potency of heat pain leg retraction response of the lisinopril group was significantly shorter than that pf the diabetic control group (P < 0.05). The pathological changes of the lisinopril group were milder than those of the other groups. The SOD level and the Na(+)K(+)-ATPase activity of the diabetic group were significantly lower than those of the normal control group, and the MDA of the diabetic group was significantly higher than those of the other 2 groups (all P < 0.05). And the SOD level and Na(+)K(+)-ATPase activity of the lisinopril group were significantly higher than those of the diabetic control group, and the MDA level of the lisinopril group was significantly lower than that of the diabetic control Wang, Lei; Chopp, Michael; Szalad, Alexandra; Lu, XueRong; Jia, LongFei; Lu, Mei; Zhang, Rui Lan; Zhang, Zheng Gang We previously demonstrated that treatment of diabetic peripheral neuropathy with the short (4 hours) half-life phosphodiesterase 5 (PDE5) inhibitor, sildenafil, improved functional outcome in diabetic db/db mice. To further examine the effect of PDE5 inhibition on diabetic peripheral neuropathy, we investigated the effect of another potent PDE5 inhibitor, tadalafil, on diabetic peripheral neuropathy. Tadalafil is pharmacokinetically distinct from sildenafil and has a longer half-life (17+hours) than sildenafil. Diabetic mice (BKS.Cg-m+/+Leprdb/J, db/db) at age 20 weeks were treated with tadalafil every 48 hours for 8 consecutive weeks. Compared with diabetic mice treated with saline, tadalafil treatment significantly improved motor and sensory conduction velocities in the sciatic nerve and peripheral thermal sensitivity. Tadalafil treatment also markedly increased local blood flow and the density of FITC-dextran perfused vessels in the sciatic nerve concomitantly with increased intraepidermal nerve fiber density. Moreover, tadalafil reversed the diabetes-induced reductions of axon diameter and myelin thickness and reversed the diabetes-induced increased g-ratio in the sciatic nerve. Furthermore, tadalafil enhanced diabetes-reduced nerve growth factor (NGF) and platelet-derived growth factor-C (PDGF-C) protein levels in diabetic sciatic nerve tissue. The present study demonstrates that tadalafil increases regional blood flow in the sciatic nerve tissue, which may contribute to the improvement of peripheral nerve function and the amelioration of diabetic peripheral neuropathy. PMID:27438594 Barwick, Alex L; Tessier, John W; Janse de Jonge, Xanne; Ivers, James R; Chuter, Vivienne H This study examined whether the presence of peripheral sensory neuropathy or cardiac autonomic deficits is associated with postocclusive reactive hyperemia (reflective of microvascular function) in the diabetic foot. 99 participants with type 2 diabetes were recruited into this cross-sectional study. The presence of peripheral sensory neuropathy was determined with standard clinical tests and cardiac autonomic function was assessed with heart rate variation testing. Postocclusive reactive hyperemia was measured with laser Doppler in the hallux. Multiple hierarchical regression was performed to examine relationships between neuropathy and the peak perfusion following occlusion and the time to reach this peak. Peripheral sensory neuropathy predicted 22% of the variance in time to peak following occlusion (p<0.05), being associated with a slower time to peak but was not associated with the magnitude of the peak. Heart rate variation was not associated with the postocclusive reactive hyperemia response. This study found an association between the presence of peripheral sensory neuropathy in people with diabetes and altered microvascular reactivity in the lower limb. Barwick, Alex L; Tessier, John W; Janse de Jonge, Xanne; Ivers, James R; Chuter, Vivienne H Objective This study examined whether the presence of peripheral sensory neuropathy or cardiac autonomic deficits is associated with postocclusive reactive hyperemia (reflective of microvascular function) in the diabetic foot. Research design and methods 99 participants with type 2 diabetes were recruited into this cross-sectional study. The presence of peripheral sensory neuropathy was determined with standard clinical tests and cardiac autonomic function was assessed with heart rate variation testing. Postocclusive reactive hyperemia was measured with laser Doppler in the hallux. Multiple hierarchical regression was performed to examine relationships between neuropathy and the peak perfusion following occlusion and the time to reach this peak. Results Peripheral sensory neuropathy predicted 22% of the variance in time to peak following occlusion (p<0.05), being associated with a slower time to peak but was not associated with the magnitude of the peak. Heart rate variation was not associated with the postocclusive reactive hyperemia response. Conclusions This study found an association between the presence of peripheral sensory neuropathy in people with diabetes and altered microvascular reactivity in the lower limb. PMID:27486520 Xiao, W. H.; Zheng, H.; Bennett, G. J. Anti-neoplastic agents in the platinum-complex, taxane, vinca alkaloid, and proteasome inhibitor classes induce a dose-limiting, chronic, distal, symmetrical, sensory peripheral neuropathy that is often accompanied by neuropathic pain. Clinical descriptions suggest that these conditions are very similar but clinical data are insufficient to determine the degree of similarity and to determine if they share common pathophysiological mechanisms. Animal models do not have the limitations of clinical studies and so we have characterized a rat model of chronic painful peripheral neuropathy induced by a platinum-complex agent, oxaliplatin, in order to compare it to a previously characterized model of chronic painful peripheral neuropathy induced by a taxane agent, paclitaxel. The oxaliplatin model evokes mechano-allodynia, mechano-hyperalgesia, and cold-allodynia that have a delayed onset, gradually increasing severity, a distinct delay to peak severity, and duration of about 2.5 months. There is no effect on heat sensitivity. EM analyses found no evidence for axonal degeneration in peripheral nerve and there is no up-regulation of activating transcription factor-3 in the lumbar dorsal root ganglia. There is a statistically significant loss of intraepidermal nerve fibers in the plantar hind paw skin. Oxaliplatin treatment causes a significant increase in the incidence of swollen and vacuolated mitochondria in peripheral nerve axons, but not in their Schwann cells. Nerve conduction studies found significant slowing of sensory axons, but no change in motor axons. Single fiber recordings found an abnormal incidence of A- and C-fibers with irregular, low-frequency spontaneous discharge. Prophylactic dosing with two drugs that are known to protect mitochondria, acetyl-L-carnitine and olesoxime, significantly reduced the development of pain hypersensitivity. Our results are very similar to those obtained previously with paclitaxel and support the hypothesis that these two Habib, Ali A; Brannagan, Thomas H Diabetes is the leading cause of peripheral neuropathy globally. Duration of diabetes, glycemic control, and preexisting cardiovascular risk factors independently correlate with the development and progression of diabetic peripheral neuropathy as well as cardiovascular autonomic neuropathy. The pathogenesis of diabetic neuropathy remains unclear, although insulin resistance, oxidative stress, mitochondrial dysfunction, abnormal glucose metabolism, advanced glycation end products, neurotrophic factors, and protein kinase C activation all may play a role. Strict glycemic control remains the only available treatment option, although other treatments are in development. Multiple options are available for symptom management. In this article, we review factors associated with development and progression of diabetic neuropathy and discuss available treatment options. Celikbilek, Asuman; Tanik, Nermin; Sabah, Seda; Borekci, Elif; Akyol, Lutfi; Ak, Hakan; Adam, Mehmet; Suher, Murat; Yilmaz, Neziha Evidence suggests that peripheral nerve injury occurs during the early stages of disease with mild glycemic dysregulation. Two proteins, neuron-specific enolase (NSE) and neurofilament light chain (NFL), have been examined previously as possible markers of neuronal damage in the pathophysiology of neuropathies. Herein, we aimed to determine the potential value of circulatory NSE and NFL mRNA levels in prediabetic patients and in those with peripheral neuropathy. This prospective clinical study included 45 prediabetic patients and 30 age- and sex-matched controls. All prediabetic patients were assessed with respect to diabetes-related microvascular complications, such as peripheral neuropathy, retinopathy and nephropathy. mRNA levels of NSE and NFL were determined in the blood by real-time polymerase chain reaction. NSE mRNA levels were similar between prediabetic and control groups (p > 0.05), whereas NFL mRNA levels were significantly higher in prediabetics than in controls (p < 0.001). NSE mRNA levels did not significantly differ between prediabetic patients with and without peripheral neuropathy (p > 0.05), while NFL mRNA levels were significantly higher in prediabetics with peripheral neuropathy than in those without (p = 0.038). According to correlation analysis, NFL mRNA levels were positively correlated with the Douleur Neuropathique 4 questionnaire score in prediabetic patients (r = 0.302, p = 0.044). This is the first study to suggest blood NFL mRNA as a surrogate marker for early prediction of prediabetic peripheral neuropathy, while NSE mRNA levels may be of no diagnostic value in prediabetic patients. Song, Tieying; Zhao, Jianhui; Ma, Xiaojing; Zhang, Zaiwang; Jiang, Bo; Yang, Yunliang The neurobiological mechanisms of obesity-induced peripheral neuropathy are poorly understood. We evaluated the role of Sigma-1 receptor (Sig-1R) and NMDA receptor (NMDARs) in the spinal cord in peripheral neuropathy using an animal model of high fat diet-induced diabetes. We examined the expression of Sig-1R and NMDAR subunits GluN2A and GluN2B along with postsynaptic density protein 95 (PSD-95) in the spinal cord after 24-week HFD treatment in both wild-type and Sig-1R-/- mice. Finally, we examined the effects of repeated intrathecal administrations of selective Sig-1R antagonists BD1047 in HFD-fed wild-type mice on peripheral neuropathy. Wild-type mice developed tactile allodynia and thermal hypoalgesia after 24-week HFD treatment. HFD-induced peripheral neuropathy correlated with increased expression of GluN2A and GluN2B subunits of NMDARs, PDS-95, and Sig-1R, as well as increased Sig-1R-NMDAR interaction in the spinal cord. In contrast, Sig-1R-/- mice did not develop thermal hypoalgesia or tactile allodynia after 24-week HFD treatment, and the levels of GluN2A, GluN2B, and PSD-95 were not altered in the spinal cord of HFD-fed Sig-1R-/- mice. Finally, repeated intrathecal administrations of selective Sig-1R antagonists BD1047 in HFD-fed wild-type mice attenuated peripheral neuropathy. Our results suggest that obesity-associated peripheral neuropathy may involve Sig-1R-mediated enhancement of NMDAR expression in the spinal cord. Bracewell, N; Game, F; Jeffcoate, W; Scammell, B E Current National Institute for Health and Clinical Excellence guidelines state that patients with diabetes should have annual examination of their feet to exclude signs of sensory impairment. The VibraTip is a new disposable device producing a vibratory stimulus, which has been developed in order to screen for peripheral sensory neuropathy in diabetes. This study was designed to evaluate the device by assessing intra-rater reliability and comparing the ability of the VibraTip to detect or exclude peripheral sensory neuropathy with other bedside methods. One hundred and forty-one patients with diabetes (Type 1 or Type 2) were examined for diabetic peripheral sensory neuropathy using a Neurothesiometer, 10-g monofilament, a 128-Hz tuning fork, a Neurotip™ and a VibraTip. The failure to perceive the Neurosthesiometer stimulus at ≥ 25 V in either foot was considered the reference method for the presence of peripheral sensory neuropathy. Receiver operating characteristic curves were produced for each device and the sensitivity, specificity, predictive values and likelihood ratios for the diagnosis of peripheral sensory neuropathy were calculated. Repeat testing with the VibraTip was performed in 18 patients and intra-rater reliability assessed using Cronbach alpha. Analysis of the area under the receiver operating characteristic curves showed that the 10-g monofilament was significantly better than the 128-Hz tuning fork (P = 0.0056) and the Neurotip (P = 0.0022), but was no different from the VibraTip (P = 0.3214). The alpha coefficient for the VibraTip was calculated to be 0.882, indicating good reliability. The VibraTip is a device comparable with the 10-g monofilament and therefore could be considered a useful tool for screening for peripheral sensory neuropathy in diabetes. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK. Tu, Yiji; Lineaweaver, William Charles; Chen, Zenggan; Hu, Junda; Mullins, Fred; Zhang, Feng Background Over the last decade, surgical decompression procedures have been commonly used in the treatment of diabetic peripheral neuropathy. However, the effectiveness of them remains to be proved. Methods A comprehensive literature search of databases including PubMed-Medline, Ovid-EMBASE, and Cochrane Library was performed to collect the related literatures. The Medical Subject Headings used were "diabetic neuropathy," "surgical decompression," and "outcomes." The methodological index for nonrandomized studies was adopted for assessing the studies included in this review. Analyses were performed with Review Manager (Version 5.3, Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration, 2014). Results A total of 12 literatures (including 8 prospective and 4 retrospective) encompassing 1,825 patients with DPN were included in the final analysis. Only one literature was identified as a randomized controlled trial. The remaining 11 literatures were observational studies; 7 of them were classified as upper-extremity nerve decompression group and 4 of them were classified as lower-extremity nerve decompression group. Meta-analysis shows that Boston questionnaire symptom severity and functional status of upper extremities, and distal motor latency and sensory conduction velocity of median nerve of DPN patients are significantly improved after carpal tunnel release. Besides, visual analog scale and two-point discrimination are considered clinically and statistically significant in lower extremities after operation. Conclusions The findings from our review have shown the efficacy of surgical decompression procedures in relieving the neurologic symptoms and restoring the sensory deficits in DPN patients. As there are few high-quality randomized controlled trials or well-designed prospective studies, more data are needed to elucidate the role of surgical procedures for DPN treatment in the future. Tesfaye, Solomon; Selvarajah, Dinesh Diabetic peripheral neuropathy (DPN) affects up to 50% of patients with diabetes and is a major cause of morbidity and increased mortality. Its clinical manifestations include painful neuropathic symptoms and insensitivity, which increases the risk for burns, injuries and foot ulceration. Several recent studies have implicated poor glycaemic control, duration of diabetes, hyperlipidaemia (particularly hypertryglyceridaemia), elevated albumin excretion rates and obesity as risk factors for the development of DPN. Although there is now strong evidence for the importance of nerve microvascular disease in the pathogenesis of DPN, the risk factors for painful DPN are not known. However, emerging evidence regarding the central correlates of painful DPN is now afforded by brain imaging. The diagnosis of DPN begins with a careful history of sensory and motor symptoms. The quality and severity of neuropathic pain if present should be assessed using a suitable scale. Clinical examination should include inspection of the feet and evaluation of reflexes and sensory responses to vibration, light touch, pinprick and the 10-g monofilament. Glycaemic control and addressing cardiovascular risk is now considered important in the overall management of the neuropathic patient. Pharmacological treatment of painful DPN includes tricyclic compounds, serotonin-norepinephrine reuptake inhibitors (e.g. duloxetine), anticonvulsants (e.g. pregabalin), opiates, membrane stabilizers, the antioxidant alpha lipoic acid and others. Over the past 7 years, new agents with perhaps less side effect profiles have immerged. Management of patients with painful neuropathy must be tailored to individual requirements and will depend on the presence of other co-morbidities. There is limited literature with regard to combination treatment. ... from the NHLBI on Twitter. What Are the Signs and Symptoms of Peripheral Artery Disease? Many people ... flow, so the symptoms will go away. Other Signs and Symptoms Other signs and symptoms of P. ... Illigens, Ben M.W.; Siepmann, Timo; Roofeh, Joe; Gibbons, Christopher H. Small fiber neuropathy is common in a number of systemic diseases and is often challenging to diagnose. Laser-Doppler Imaging (LDI) is a test of small fiber neurovascular function that can quantify the integrity of the vasomotor C-fiber mediated axon-reflex, but no standardized method of analysis exists. We developed a novel LDI analysis technique and tested it in a human model of small fiber neuropathy. Eighteen healthy subjects (age 24±3 years) underwent LDI testing to assess the axon-mediated flare area in response to 10% acetylcholine iontophoresis. LDI measurements were taken before and longitudinally after a 48-hour application of 0.1% capsaicin (to cause a transient small fiber neuropathy) on the skin of the thigh; placebo cream was placed on the contralateral thigh as a control. We compared our new LDI image analysis technique to two previously published methods. The new LDI analysis technique was the only method to show a consistent difference in axon-reflex area between capsaicin treated and placebo treated skin on all testing days (p<0.05) with maximum attenuation of the flare area immediately post-application (438 ±298 mm2 vs. 824 ±375 mm2, p<0.05). In conclusion, this study demonstrates that our novel flare area method for LDI analysis can detect neurovascular dysfunction in a model of small fiber neuropathy, is an improvement over existing methods, and may supplement clinical assessment of small fiber neuropathy. PMID:23850386 Illigens, Ben M W; Siepmann, Timo; Roofeh, Joseph; Gibbons, Christopher H Small fiber neuropathy is common in a number of systemic diseases and is often challenging to diagnose. Laser Doppler imaging (LDI) is a test of small fiber neurovascular function that can quantify the integrity of the vasomotor C-fiber mediated axon-reflex, but no standardized method of analysis exists. We developed a novel LDI analysis technique and tested it in a human model of small fiber neuropathy. Eighteen healthy subjects (age 24 ± 3 years) underwent LDI testing to assess the axon-mediated flare area in response to 10% acetylcholine iontophoresis. LDI measurements were taken before and longitudinally after a 48-hour application of 0.1% capsaicin (to cause a transient small fiber neuropathy) on the skin of the thigh; placebo cream was placed on the contralateral thigh as a control. We compared our new LDI image analysis technique to two previously published methods. The new LDI analysis technique was the only method to show a consistent difference in axon-reflex area between capsaicin treated and placebo treated skin on all testing days (p<0.05) with maximum attenuation of the flare area immediately post-application (438 ± 298 mm(2) vs. 824 ± 375 mm(2), p<0.05). In conclusion, this study demonstrates that our novel flare area method for LDI analysis can detect neurovascular dysfunction in a model of small fiber neuropathy, is an improvement over existing methods, and may supplement clinical assessment of small fiber neuropathy. Peng, L; Bu, Z; Ye, X; Zhou, Y; Zhao, Q Nab-paclitaxel, a Cremophor EL-free formulation of paclitaxel, is used to treat various malignancies. Peripheral neuropathy is one of its major toxicities, although the overall incidence remains unclear. We performed a meta-analysis to calculate the incidence of peripheral neuropathy in cancer patients treated with nab-paclitaxel and to compare the relative risk (RR) with conventional taxanes. The electronic databases were searched for relevant clinical trials. Eligible studies included phase II and III prospective clinical trials of cancer patients treated with nab-paclitaxel with toxicity profile on peripheral neuropathy. Statistical analyses were done to calculate summary incidences, RRs and 95% confidence intervals (CI), using fixed-effects or random-effects models based on the heterogeneity of the included studies. Nineteen trials were selected for the meta-analysis, yielding a total of 2878 cancer patients. The overall incidences of peripheral neuropathy (all-grade) was 51.0% (95% CI: 45.1-57.6%), and that of high-grade peripheral neuropathy was 12.4% (9.8-15.7%). The RRs of peripheral neuropathy of nab-paclitaxel compared to taxanes were not increased for all-grade and high-grade peripheral neuropathy. Nab-paclitaxel is associated with an increased risk of developing peripheral neuropathy. Future clinical studies are still needed to investigate the risk reduction and possible use of nab-paclitaxel. © 2015 John Wiley & Sons Ltd. Kernozek, Thomas W; Greany, John F; Heizler, Cassandra We investigated plantar loading asymmetry during gait in American Indians with and without diabetes and with diabetes and peripheral neuropathy. A convenience sample of 96 American Indians with and without diabetes was divided into three groups: 20 with diabetes and peripheral neuropathy, 16 with diabetes without peripheral neuropathy, and 60 with no history of diabetes (control group). Plantar loading was measured during barefoot walking across a pressure platform. Five trials were collected per foot during level walking at a self-selected speed using the two-step method. Asymmetry in peak pressure-time integral and peak plantar pressure were calculated from ten plantar regions and compared among groups. Significant pressure-time integral asymmetry occurred across the forefoot regions in American Indians with diabetes and peripheral neuropathy compared with the other two groups. Significant peak plantar pressure asymmetry occurred in the third metatarsal region in both groups with diabetes (with and without peripheral neuropathy) compared with the control group. Overall, American Indians with diabetes seemed to show greater asymmetry in plantar loading variables across the forefoot region compared with those in the control group. Specifically, individuals with diabetes and peripheral neuropathy had the greatest amount of forefoot pressure-time integral asymmetry. Significant peak plantar pressure asymmetry occurred in the third metatarsal region of the forefoot in those with diabetes with and without peripheral neuropathy. Loading asymmetry may play a role in the development of foot ulcers in the forefoot region of American Indians with peripheral neuropathy and diabetes. Antoine, J.; Mosnier, J.; Absi, L.; Convers, P.; Honnorat, J.; Michel, D. OBJECTIVE—When to suspect a paraneoplastic disorder is a puzzling problem that has not recently been studied in a large series of patients referred for peripheral neuropathy. METHODS—From 422 consecutive patients with peripheral neuropathy, 26 were analysed who concomitantly had carcinoma but no tumorous infiltration, drug toxicity, or cachexia. Their clinical, pathological, and electrophysiological data were analysed according to the presence of anti-onconeural antibodies, the latency between presentation and cancer diagnosis, and the incidence of carcinoma in the corresponding types of neuropathy of the population of 422patients. RESULTS—Seven patients (group I) had anti-onconeural antibodies (six anti-Hu, one anti-CV2) and 19 did not (groups IIA and B). In group I, subacute sensory neuropathy (SSN) was the most frequent but other neuropathies including demyelinating neuropathies were present. Patients in group II A had a short latency (mean 7.88months), and a rapidly and usually severe neuropathy which corresponded in 11/14 to an established inflammatory disorder including neuropathy with encephalomyelitis, mononeuritis multiplex, and acute or chronic inflammatory demyelinating polyneuropathy (CIDP). Patients in group IIB had a long latency (mean 8.4 years) and a very chronic disorder corresponding in four of five to an axonal non-inflammatory polyneuropathy. In this population, the incidence of carcinoma occurring with a short latency was 47% in sensory neuronopathy, 1.7% in Guillain-Barré syndrome, 10% in mononeuritis multiplex and CIDP, and 4.5% in axonal polyneuropathy. CONCLUSIONS—Paraneoplastic neuropathies associated with carcinoma are heterogeneous disorders. Neuropathies occurring with a long latency with tumours probably resulted from a coincidental association. Neuropathies which occurred within a few years of the tumour evolved rapidly and corresponded mostly to inflammatory disorders. As dysimmune neuropathies are probably Bardini, Michela; Fazio, Grazia; Chiorazzi, Alessia; Meregalli, Cristina; Oggioni, Norberto; Shanks, Kathleen; Quartu, Marina; Serra, Maria Pina; Sala, Barbara; Cavaletti, Guido; Dorsey, Susan G. Bortezomib is the first proteasome inhibitor with significant antineoplastic activity for the treatment of relapsed/refractory multiple myeloma as well as other hematological and solid neoplasms. Peripheral neurological complications manifesting with paresthesias, burning sensations, dysesthesias, numbness, sensory loss, reduced proprioception and vibratory sensitivity are among the major limiting side effects associated with bortezomib therapy. Although bortezomib-induced painful peripheral neuropathy is clinically easy to diagnose and reliable models are available, its pathophysiology remains partly unclear. In this study we used well-characterized immune-competent and immune-compromised mouse models of bortezomib-induced painful peripheral neuropathy. To characterize the drug-induced pathological changes in the peripheral nervous system, we examined the involvement of spinal cord neuronal function in the development of neuropathic pain and investigated the relevance of the immune response in painful peripheral neuropathy induced by bortezomib. We found that bortezomib treatment induced morphological changes in the spinal cord, dorsal roots, dorsal root ganglia (DRG) and peripheral nerves. Neurophysiological abnormalities and specific functional alterations in Aδ and C fibers were also observed in peripheral nerve fibers. Mice developed mechanical allodynia and functional abnormalities of wide dynamic range neurons in the dorsal horn of spinal cord. Bortezomib induced increased expression of the neuronal stress marker activating transcription factor-3 in most DRG. Moreover, the immunodeficient animals treated with bortezomib developed a painful peripheral neuropathy with the same features observed in the immunocompetent mice. In conclusion, this study extends the knowledge of the sites of damage induced in the nervous system by bortezomib administration. Moreover, a selective functional vulnerability of peripheral nerve fiber subpopulations was found as well as Jambart, S; Ammache, Z; Haddad, F; Younes, A; Hassoun, A; Abdalla, K; Selwan, C Abou; Sunna, N; Wajsbrot, D; Youseif, E The prevalence of painful diabetic peripheral neuropathy (DPN) was evaluated in type 1 or type 2 diabetes mellitus patients (n = 4097) attending outpatient clinics across the Middle East. Overall, 53.7% of 3989 patients with DN4 data met the criteria for painful DPN (Douleur Neuropathique-4 [DN4] scores ≥ 4). Significant predictors of painful DPN included long history (≥ 10 years) of diabetes (odds ratio [OR] 2.43), age ≥ 65 years (OR 2.13), age 50 - 64 years (OR 1.75), presence of type 1 versus type 2 diabetes (OR 1.59), body mass index > 30 kg/m(2) (OR 1.35) and female gender (OR 1.27). Living in one of the Gulf States was associated with the lowest odds of having painful DPN (OR 0.44). The odds of painful DPN were highest among patients with peripheral vascular disease (OR 4.98), diabetic retinopathy (OR 3.90) and diabetic nephropathy (OR 3.23). Because of the high prevalence and associated suffering, disability and economic burden of painful DPN, it is important that diabetic patients are periodically screened, using a simple instrument such as the DN4, and receive appropriate treatment if symptoms develop. Shy, Michael E Development and maintenance of PNS myelin depends on continual signaling from axons ensheathed by myelin. Recent advances have demonstrated the roles of neuregulin 1 type III, Erb2/3 and intracellular signal transduction pathways in inducing Schwann cell myelination. Alternatively, maintenance of myelinated axons depends on healthy myelinating Schwann cells. Axonal degeneration is a feature of virtually all inherited demyelinating neuropathies and in many cases is more responsible for clinical impairment than the primary demyelination. Signaling mechanisms through which demyelinating Schwann cells damage axons are not well understood. In this review several examples of potential mechanisms by which demyelinating neuropathies damage axons will be presented. Understanding the molecular basis of Schwann cell-axonal interactions will not only increase the understanding of PNS biology but also identify therapeutic targets for inherited neuropathies. Shy, Michael E Charcot-Marie-Tooth disease type 1B (CMT1B) is caused by mutations in the major PNS myelin protein myelin protein zero (MPZ). MPZ is a member of the immunoglobulin supergene family and functions as an adhesion molecule helping to mediate compaction of PNS myelin. Mutations in MPZ appear to either disrupt myelination during development, leading to severe early onset neuropathies, or to disrupt axo-glial interactions leading to late onset neuropathies in adulthood. Identifying molecular pathways involved in early and late onset CMT1B will be crucial to understand how MPZ mutations cause CMT1B so that rational therapies for both early and late onset neuropathies can be developed. The reliability and validity of a modified total neuropathy score-reduced and neuropathic pain severity items when used to measure chemotherapy-induced peripheral neuropathy in patients receiving taxanes and platinums. Smith, Ellen M Lavoie; Cohen, Jeffrey A; Pett, Marjorie A; Beck, Susan L Assessment of chemotherapy-induced peripheral neuropathy signs and symptoms has been hampered because of the lack of simple, reliable, and valid measures. The study objective was to examine the internal consistency and interrater reliability as well as the structural validity of a 5-component total neuropathy score-reduced (TNSr) variant and a chemotherapy-induced neuropathy-specific Neuropathic Pain Scale. One hundred seventeen outpatients receiving taxanes or platinums were assessed by a consistent nurse practitioner using the 2 instruments. Ten subjects participated in interrater reliability testing. Mean scores and SDs for individual items were low. The strength item was deleted because of low interitem correlations and a floor effect. The reflex item was deleted because of low interitem correlations and its negative influence on Cronbach alpha. Pin sensibility was deleted because of low factor loadings. The TNSr-short form and the chemotherapy-induced neuropathy-specific Neuropathic Pain Scale formed 2 distinct factors, providing evidence of structural validity. Cronbach alpha's for the 2 instruments were .80 and .96, respectively. The TNSr interrater reliability results suggested acceptable rater concordance, but minor revisions could further improve scoring precision. Clinimetric evidence supports the use of 2 new instruments when monitoring taxane- and platinum-related neuropathy and pain. Further instrument modifications are recommended, followed by additional testing in diverse populations. With these new instruments, nurses can more easily incorporate prospective neuropathy assessment into daily clinical practice. The outcome will be improved symptom awareness by oncology clinicians and patients, leading to fewer chemotherapy-induced peripheral neuropathy-related devastating effects on functionality and quality of life. Goss, James R; Stolz, Donna Beer; Robinson, Andria Rasile; Zhang, Mingdi; Arbujas, Norma; Robbins, Paul D; Glorioso, Joseph C; Niedernhofer, Laura J Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1(-/Δ) mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1(-/Δ) mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies. Taylor, Sean W; Laughlin, Ruple S; Kumar, Neeraj; Goodman, Brent; Klein, Christopher J; Dyck, Peter J; Dyck, P James B Myelopathy is considered the most common neurological complication of copper deficiency. Concurrent peripheral neuropathy has been recognised in association with copper deficiency but has not been well characterised. To characterise the clinical, physiological and pathological features of copper-deficient peripheral neuropathy. Patients with simultaneous copper deficiency (<0.78 μg/mL) and peripheral neuropathy seen at the Mayo Clinic from 1985 to 2005 were identified. 34 patients were identified (median age 55 years, range 36-78) including 24 women and 10 men. Myelopathy was found in 21 patients. Median serum copper level was 0.11 μg/mL (range 0-0.58). The most frequent clinical and electrophysiological pattern of neuropathy was a sensory predominant length-dependent peripheral neuropathy (71%). Somatosensory evoked potentials demonstrated central slowing supporting myelopathy (96%). Quantitative sensory testing demonstrated both small and large fibre involvement (100%). Autonomic reflex screens (77%) and thermoregulatory sweat test (67%) confirmed sudomotor dysfunction. 14 cutaneous nerve biopsies revealed loss of myelinated nerve fibres (86%), increased regenerative clusters (50%), increased rates of axonal degeneration (91%) and increased numbers of empty nerve strands (73%). 71% of biopsies demonstrated epineurial perivascular inflammation. An axonal, length-dependent sensory predominant peripheral neuropathy causing sensory ataxia is characteristic of copper deficiency usually co-occurring with myelopathy. Neurophysiological testing confirms involvement of large, greater than small fibres. The pathological findings suggest axonal degeneration and repair. Inflammatory infiltrates are common but are small and of doubtful pathological significance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Prinsloo, Sarah; Novy, Diane; Driver, Larry; Lyle, Randall; Ramondetta, Lois; Eng, Cathy; McQuade, Jennifer; Lopez, Gabriel; Cohen, Lorenzo Chemotherapy-induced peripheral neuropathy (CIPN) is a significant problem for cancer patients, and there are limited treatment options for this often debilitating condition. Neuromodulatory interventions could be a novel modality for patients trying to manage CIPN symptoms; however, they are not yet the standard of care. This study examined whether electroencephalogram (EEG) neurofeedback (NFB) could alleviate CIPN symptoms in survivors. This was a randomized controlled trial with survivors assigned to an NFB group or a wait-list control (WLC) group. The NFB group underwent 20 sessions of NFB, in which visual and auditory rewards were given for voluntary changes in EEGs. The Brief Pain Inventory (BPI) worst-pain item was the primary outcome. The BPI, the Pain Quality Assessment Scale, and EEGs were collected before NFB and again after treatment. Outcomes were assessed with general linear modeling. Cancer survivors with CIPN (average duration of symptoms, 25.3 mo), who were mostly female and had a mean age of 62.5 years, were recruited between April 2011 and September 2014. One hundred percent of the participants starting the NFB program completed it (30 in the NFB group and 32 in the WLC group). The NFB group demonstrated greater improvement than the controls on the BPI worst-pain item (mean change score, -2.43 [95% confidence interval, -3.58 to -1.28] vs 0.09 [95% confidence interval, -0.72 to -0.90]; P =·.001; effect size, 0.83). NFB appears to be effective at reducing CIPN symptoms. There was evidence of neurological changes in the cortical location and in the bandwidth targeted by the intervention, and changes in EEG activity were predictive of symptom reduction. Cancer 2017;123:1989-1997. © 2017 American Cancer Society. © 2017 American Cancer Society. Petropoulos, Ioannis N; Alam, Uazman; Fadavi, Hassan; Marshall, Andrew; Asghar, Omar; Dabbah, Mohammad A; Chen, Xin; Graham, James; Ponirakis, Georgios; Boulton, Andrew J M; Tavakoli, Mitra; Malik, Rayaz A To assess the diagnostic validity of a fully automated image analysis algorithm of in vivo confocal microscopy images in quantifying corneal subbasal nerves to diagnose diabetic neuropathy. One hundred eighty-six patients with type 1 and type 2 diabetes mellitus (T1/T2DM) and 55 age-matched controls underwent assessment of neuropathy and bilateral in vivo corneal confocal microscopy (IVCCM). Corneal nerve fiber density (CNFD), branch density (CNBD), and length (CNFL) were quantified with expert, manual, and fully-automated analysis. The areas under the curve (AUC), odds ratios (OR), and optimal thresholds to rule out neuropathy were estimated for both analysis methods. Neuropathy was detected in 53% of patients with diabetes. A significant reduction in manual and automated CNBD (P < 0.001) and CNFD (P < 0.0001), and CNFL (P < 0.0001) occurred with increasing neuropathic severity. Manual and automated analysis methods were highly correlated for CNFD (r = 0.9, P < 0.0001), CNFL (r = 0.89, P < 0.0001), and CNBD (r = 0.75, P < 0.0001). Manual CNFD and automated CNFL were associated with the highest AUC, sensitivity/specificity and OR to rule out neuropathy. Diabetic peripheral neuropathy is associated with significant corneal nerve loss detected with IVCCM. Fully automated corneal nerve quantification provides an objective and reproducible means to detect human diabetic neuropathy. Petropoulos, Ioannis N.; Alam, Uazman; Fadavi, Hassan; Marshall, Andrew; Asghar, Omar; Dabbah, Mohammad A.; Chen, Xin; Graham, James; Ponirakis, Georgios; Boulton, Andrew J. M.; Tavakoli, Mitra; Malik, Rayaz A. Purpose. To assess the diagnostic validity of a fully automated image analysis algorithm of in vivo confocal microscopy images in quantifying corneal subbasal nerves to diagnose diabetic neuropathy. Methods. One hundred eighty-six patients with type 1 and type 2 diabetes mellitus (T1/T2DM) and 55 age-matched controls underwent assessment of neuropathy and bilateral in vivo corneal confocal microscopy (IVCCM). Corneal nerve fiber density (CNFD), branch density (CNBD), and length (CNFL) were quantified with expert, manual, and fully-automated analysis. The areas under the curve (AUC), odds ratios (OR), and optimal thresholds to rule out neuropathy were estimated for both analysis methods. Results. Neuropathy was detected in 53% of patients with diabetes. A significant reduction in manual and automated CNBD (P < 0.001) and CNFD (P < 0.0001), and CNFL (P < 0.0001) occurred with increasing neuropathic severity. Manual and automated analysis methods were highly correlated for CNFD (r = 0.9, P < 0.0001), CNFL (r = 0.89, P < 0.0001), and CNBD (r = 0.75, P < 0.0001). Manual CNFD and automated CNFL were associated with the highest AUC, sensitivity/specificity and OR to rule out neuropathy. Conclusions. Diabetic peripheral neuropathy is associated with significant corneal nerve loss detected with IVCCM. Fully automated corneal nerve quantification provides an objective and reproducible means to detect human diabetic neuropathy. PMID:24569580 Perbellini, L; De Grandis, D; Marchiori, L; Olivato, D; Bertolasi, L Nine cases of local neuropathy are described in shoe-manufacture workers. Clinical and electrophysiological examination excluded diseases such as toxic polyneuropathies due to n-hexane. Specific lesions of the ulnar nerve were located near the elbow where the forced and uncomfortable posture facilitated the compression of the nerve in the cubital tunnel. The severity of the neuropathies ranged from relatively slight, with paresthesia of some of the fingers, to evident hypotrophy of the inter-osseous muscles of the hand. All the 9 cases sewed shoe uppers using sewing machines operating 25 cm above the arm support, thus obliging the operator to work with one or both elbows resting on the support, with the arms and shoe-upper held up. Five cases presented a neuropathy of the right arm, 3 of the left arm, and in one case the lesions were bilateral. The features of the work station are described and the possible promoting factors and the ergonomic pathogenesis of these neuropathies are discussed. Stubblefield, Michael D; McNeely, Margaret L; Alfano, Catherine M; Mayer, Deborah K Chemotherapy-induced peripheral neuropathy (CIPN) results from damage to or dysfunction of the peripheral nerves. The development of CIPN is anticipated for the majority of breast cancer patients who receive neurotoxic chemotherapy, depending on the agent used, dose, and schedule. Sensory symptoms often predominate and include numbness, tingling, and distal extremity pain. Weakness, gait impairment, loss of functional abilities, and other deficits may develop with more severe CIPN. This article outlines a prospective surveillance model for physical rehabilitation of women with breast cancer who develop CIPN. Rehabilitative efforts for CIPN start at the time of breast cancer diagnosis and treatment planning. The prechemotherapy evaluation identifies patients with preexisting peripheral nervous system disorders that may place them at higher risk for the development of CIPN. This clinical evaluation should include a history focusing on symptoms and functional activities as well as a physical examination that objectively assesses the patient's strength, sensation, reflexes, and gait. Ongoing surveillance following the initiation of a neurotoxic agent is important to monitor for the development and progression of symptoms associated with CIPN, and to ensure its resolution over the long term. CIPN is managed best by a multidisciplinary team approach. Early identification of symptoms will ensure appropriate referral and timely symptom management. The prospective surveillance model promotes a patient-centered approach to care, from pretreatment through survivorship and palliative care. In this way, the model offers promise in addressing and minimizing both the acute and long-term morbidity associated with CIPN. Jung, M; Rein, N; Fuchs, B Background: Chemotherapy-induced peripheral neuropathy is a frequent side-effect of drugs that are used in the treatment of cancer. Affected individuals can suffer from motor, sensory or autonomy nerve damage. Further medication is used for the treatment of CIPN which can cause further side-effects. Patients should be offered physical therapy treatment to relieve the symptoms. Objective: The aim of this article is to give an overview of available literature investigating physical therapy in CIPN in pediatric oncology. Methods: To determine relevant literature, a systematic review was conducted in the databases CINAHL, The Cochrane Library, ERIC, MEDPILOT, PEDro, PsycARTICLES, PsycINFO, PubMed and DIMDI. Besides the methodological quality of the identified literature is supposed to be reviewed. Results: There is no current literature regarding the subject of this article, so no evaluation of the quality could be carried out. Although several publications concerning adults could be identified and transfer could be established for pediatrics. Conclusion: Acupuncture appeared to be effective in the treatment of CIPN in adults. Good results appeared especially regarding pain. Sensorimotor training, balance training, electrotherapy and alternative methods like Reiki and Yoga showed good results for patients symptoms. These treatment methods give a future prospect how CIPN in children can be treated successfully - but further pediatric research is necessary. © Georg Thieme Verlag KG Stuttgart · New York. Schumacher, Christie; Glosner, Scott E OBJECTIVES To assess the prevalence of painful diabetic peripheral neuropathy (DPN), evaluate the impact of DPN on patients' function and quality of life, and assess patient satisfaction with their current DPN treatment. DESIGN Cross-sectional study. SETTING Patient-centered medical home model at an internal medicine clinic in Chicago, from November 1, 2011, through November 1, 2012. PARTICIPANTS 71 patients with type 1 or type 2 diabetes aged 45 to 85 years and receiving diabetes education and medication management from the clinic pharmacist. INTERVENTION Paper survey administered to patients during clinic visits. MAIN OUTCOME MEASURES DPN history; DPN impact on activity level, sleep, and quality of life; and satisfaction with current DPN treatment. RESULTS Of the 71 participants, 22% (n = 15) reported a diagnosis of DPN from their providers; however, 54% (n = 37) reported burning, aching, or tenderness in their hands, arms, legs, or feet. More than 50% of patients with these symptoms had experienced them for more than 1 year. Fewer than one in five patients (14% [n = 5]) reporting symptoms indicative of painful DPN were receiving treatment. CONCLUSION DPN may be underdiagnosed and undertreated in this patient population, which represents a potential opportunity for pharmacists to help patients with diabetes meet their quality of care goals. Vigani, A G; Macedo-de-Oliveira, A; Pavan, M H P; Pedro, M N; Gonçales Jr, F L Hepatitis C virus (HCV) is essentially hepatotropic but its manifestations can extend beyond the liver. It can be associated with autoimmune diseases, such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune thyroiditis, and lymphoproliferative disorders. The mechanisms that trigger these manifestations are not completely understood. We describe a 48-year-old man with chronic HCV infection (circulating HCV RNA and moderate hepatitis as indicated by liver biopsy), cryoglobulinemia, and sensory and motor peripheral neuropathy. The diagnosis of multineuropathy was confirmed by clinical examination and electromyographic tests. A nerve biopsy revealed an inflammatory infiltrate in the perineurial space and signs of demyelination and axonal degeneration. The patient had no improvement of neurological symptoms with the use of analgesics and neuro-modulators. He was then treated with interferon-alpha (3 million units subcutaneously, 3 times per week) and ribavirin (500 mg orally, twice a day) for 48 weeks. Six months after the end of therapy, the patient had sustained viral response (negative HCV RNA) and remission of neurological symptoms, but cryoglobulins remained positive. A review of the literature on the pathogenesis and treatment of neurological manifestations associated with HCV infection is presented. This report underscores the need for a thorough evaluation of HCV-infected patients because of the possibility of extrahepatic manifestations. Antiviral treatment with interferon and ribavirin can be effective and should be considered in patients with neurological complications associated with HCV infection. Scofield, Amanda K.; Radfar, Lida; Ice, John; Vista, Evan; Anaya, Juan-Manuel; Houston, Glen; Lewis, David; Stone, Donald U.; Chodosh, James; Hefner, Kimberly; Lessard, Christopher J.; Moser, Kathy L.; Scofield, R. Hal Background Sjögren syndrome is a common, chronic autoimmune disease that typically produces inflammation and poor function of the salivary and lacrimal glands. Other organs can be affected, including the nervous system. Sensory peripheral neuropathy is a common manifestation of the disease. Methods Eight-eight patients attending a dry eyes-dry mouth clinic were classified as primary Sjögren syndrome and underwent a neurological examination. Anti-Ro (or SSA) and anti-La (or SSB) were determined using immunodiffusion as well as Inno-Lia and BioPlex ANA screen. Serum vitamin B12 levels were determined using an enzyme-linked microtiter plate assay. Results Twenty-seven (31%) of the 88 patients had peripheral neuropathy as defined by loss of light touch, proprioception or vibratory sensation. Anti-Ro and anti-La were found by immunodiffusion in 12 patients, and 8 of these 12 had neuropathy (χ2=8.46, p=0.0036, odds ratio = 6.0 compared to those without precipitating anti-Ro and anti-La). Of the 27 patients with only anti-Ro by immunodiffusion, 13 (48.1%) of these had neuropathy (χ2 =5.587, p=0.018 compared to those without anti-Ro). There was no relationship of the other, more sensitive measures of anti-Ro and anti-La to neuropathy. In addition, we found no association of serum vitamin B12 levels to neuropathy among these patients with Sjögren syndrome. Conclusion Sensory peripheral neuropathy is common among patients with Sjögren syndrome, and is associated with the presence of anti-Ro and anti-La when determined by immunodiffusion. PMID:22955477 Tamari, I; Goodman, R M; Sarova, I; Hertz, M; Adar, R; Zvibach, T Three unrelated Oriental Jewish families with a total of eight subjects with progressive hereditary sensory neuropathy are reported. The parents were all unaffected and because of parental consanguinity in each of the three families it is postulated that this rare neurological disorder is transmitted in an autosomal recessive manner. In one family both parents showed an abnormal response to pain stimulation with normal motor and sensory nerve conduction velocity. This response may be an expression of the carrier state for this hereditary disease. Only five other families (non-Jewish) have been reported as having this form of peripheral hereditary sensory neuropathy. These observations suggest that one type, the progressive form, of peripheral hereditary sensory neuropathy may be more common in Oriental Jews. Images PMID:6937618 Tsutsumi, Kuniaki; Kaname, Takanori; Shiraishi, Haruka; Kawashiri, Takehiro; Egashira, Nobuaki Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel-induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily) inhibited the development of mechanical allodynia induced by paclitaxel (4 mg/kg, i.p., on days 1, 3, 5 and 7) and suppressed the paclitaxel-induced increase in macrophage migration in dorsal root ganglion cells. In addition, polaprezinc did not affect the anti-tumor activity of paclitaxel in cultured cell lines or tumor-bearing mice. These results suggest a clinical indication for polaprezinc in the prevention of paclitaxel-induced neuropathy. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved. Wong, Raimond; Major, Pierre; Sagar, Stephen A prospective phase 2 study was conducted to evaluate the clinical utility of acupuncture-like transcutaneous nerve stimulation (ALTENS) for the treatment of chemotherapy-induced peripheral neuropathy (CIPN). Eligible cancer patients had a < 2 ECOG performance score, received neurotoxic chemotherapy, and developed CIPN symptoms for > two months. Randomization was used to eliminate bias in patient selection for ALTENS and was not to compare the effectiveness between the two treatments.ALTENS treatments were delivered using Codetron units. Bilateral acupuncture points included LI4 and LIV3, plus LI11 or ST36 were stimulated. Acupuncture treatments were administered to CV6, SP6, ST6, LI11, Bafeng, Baxie and selective Jing points bilaterally. Twelve treatments were delivered twice weekly over 6 to 8 weeks. The Modified Total Neuropathy Score (mTNS), Numbness Score, and Edmonton Symptom Assessment Score (ESAS) were assessed at baseline, treatment completion, plus at 3 and 6 months follow-up. The primary study endpoint was mTNS score at 6 months. We planned to recruit 23 patients into each group. After 30 patients were recruited, 2 were lost to follow-up at 3 months in the ALTENS group and 3 in the acupuncture group. The research team decided to recruit all remaining consecutive patients only to the ALTENS group to ensure an adequate evaluation of ALTENS, the primary object of evaluation. There were 27 patients in the ALTENS group, with an average symptom duration of 10 months after chemotherapy. Twenty four and 23 patients completed the 3 and 6 month follow-up respectively. The median mTNS scores were 7.1, 4.0, 3.6 and 3.1 at baseline, treatment completion, 3 and 6 months follow-up, respectively. One-way ANOVA analysis showed a significant improvement in mTNS scores (p<0.001) at 6 months. Numbness scores were also significantly improved at 6 months. ESAS pain scores and perception of well-being scores analyses were inconclusive. There were no significant reported side Truini, A; Biasiotta, A; Di Stefano, G; Leone, C; La Cesa, S; Galosi, E; Piroso, S; Pepe, A; Giordano, C; Cruccu, G The different neuropathic pain types (e.g., ongoing burning pain and allodynia) are frequent and disabling complaints in patients with peripheral neuropathies. Although the reference standard technique for diagnosing painful small-fibre neuropathies is nerve fibre density assessment by skin biopsy, the relationship between the epidermal nerve fibre (ENF) density and neuropathic pain is still unclear. In a clinical and skin biopsy study designed to investigate whether changes in ENF density are directly related to pain, we enrolled 139 consecutive patients with distal symmetric peripheral neuropathy. All patients underwent clinical examination. The Neuropathic Pain Symptom Inventory was used to distinguish the different neuropathic pain types. A skin biopsy was conducted, and ENFs were immunostained with the antiprotein gene product 9.5, and their linear density was quantified with bright-field microscopy. No difference was found in ENF density between patients with and without neuropathic pain, nor between patients with and without ongoing burning pain. Conversely, ENF density was higher in patients with provoked pains (including mechanical dynamic allodynia) than in those without. The variable association between ENF density and symptoms of neuropathic pain supports the idea that neuropathic pain symptoms arise through distinct underlying mechanisms. The lack of relationship between ongoing burning pain and ENF density suggests that this type of pain reflects factors other than loss of nociceptive afferents. The association between ENF density and provoked pain (including mechanical dynamic allodynia) suggests that this type of pain might be mediated by spared and sensitised nociceptive afferents. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. Leinders, Mathias; Üçeyler, Nurcan; Thomann, Anna; Sommer, Claudia Changes in the neuro-immune balance play a major role in the induction and maintenance of neuropathic pain. We recently reported pathophysiologically relevant alterations in skin and sural nerve cytokine expression in peripheral neuropathies of different etiologies. Immune processes and cytokine expression are under tight control of microRNAs (miRNAs). To identify potential master switches in the neuro-immune balance, we aimed at characterizing inflammation-regulating miRNA profiles in patients with peripheral neuropathies. In an unselected patient cohort with polyneuropathies of different etiologies seen at our neuromuscular center between 2014 and 2015, we determined the systemic and local relative expression of miR-21-5p, miR-146a, and miR-155. In white blood cells we found higher miR-21 (p<0.001) and miR-146a (p<0.001) expression and lower miR-155 (p<0.001) expression when compared to healthy controls. In sural nerve, miR-21 (p<0.02) was increased in painful compared to painless neuropathies. In painful neuropathies, skin biopsies from the lower leg had reduced miR-146a (p<0.001) and miR-155 (p<0.001) expression compared to the thigh. Thus, peripheral neuropathies are associated with aberrant miRNA expression in white blood cells, sural nerve, and skin. These miRNA patterns may help to identify factors that determine the painfulness of peripheral neuropathies and lead to druggable targets. Copyright © 2017 Elsevier B.V. All rights reserved. Kaplan, Gulce Sari; Torcun, Ceyda Corek; Grune, Tilman; Ozer, Nesrin Kartal; Karademir, Betul Proteasomal system plays an important role in protein turnover, which is essential for homeostasis of cells. Besides degradation of oxidized proteins, it is involved in the regulation of many different signaling pathways. These pathways include mainly cell differentiation, proliferation, apoptosis, transcriptional activation and angiogenesis. Thus, proteasomal system is a crucial target for treatment of several diseases including neurodegenerative diseases, cystic fibrosis, atherosclerosis, autoimmune diseases, diabetes and cancer. Over the last fifteen years, proteasome inhibitors have been tested to highlight their mechanisms of action and used in the clinic to treat different types of cancer. Proteasome inhibitors are mainly used in combinational therapy along with classical chemo-radiotherapy. Several studies have proved their significant effects but serious side effects such as peripheral neuropathy, limits their use in required effective doses. Recent studies focus on peripheral neuropathy as the primary side effect of proteasome inhibitors. Therefore, it is important to delineate the underlying mechanisms of peripheral neuropathy and develop new inhibitors according to obtained data. This review will detail the role of proteasome inhibition in cancer therapy and development of peripheral neuropathy as a side effect. Additionally, new approaches to prevent treatment-limiting side effects will be discussed in order to help researchers in developing effective strategies to overcome side effects of proteasome inhibitors. ... AFFAIRS 38 CFR Part 3 RIN 2900-AO32 Disease Associated With Exposure to Certain Herbicide Agents... peripheral neuropathy associated with exposure to certain herbicide agents. This amendment implements a... governing retroactive awards for certain diseases associated with herbicide exposure as required by... García, Antonio; Maestro, Iratxe Central nervous system complications following carbon monoxide (CO) poisoning are well reported in the literature but peripheral neuropathy is under-recognized. We report the clinical and electrophysiological studies of the transient peripheral neuropathy developed in a patient following acute CO intoxication. A 27-year-old woman was found unconscious with severe hypoxia and 34.5% serum level of carboxyhemoglobin. She progressed favourably after hyperbaric oxygen therapy. Neurological examination revealed bilateral pyramidal signs. The patient referred weakness and sensory abnormalities in her right foot. An electroencephalogram did not show focal abnormalities and brain magnetic resonance was normal. Needle electromyography of weak right tibialis anterior muscle showed a reduced recruitment pattern but no spontaneous activity. Electroneurographic evaluation revealed findings compatible with a motor and sensory peripheral neuropathy in nerves of both lower limbs. In few months complete clinical recovery was reached, and the electroneurography showed normality a year later Reversible peripheral neuropathy should be considered as a possible neurological complication following acute CO poisoning. The electrophysiological studies were essential for its diagnosis and follow up. ...-modifying agents, and clinical trial design. FDA intends to take this information into account in developing... peripheral neuropathy. Date and Time: The public workshop will be held on February 11, 2013, from 8:30 a.m... speaker's comments during this open public hearing may be limited by time constraints. Registration is... ... AFFAIRS 38 CFR Part 3 RIN 2900-AO32 Disease Associated With Exposure to Certain Herbicide Agents... connection for acute and sub-acute peripheral neuropathy associated with exposure to certain herbicide agents... associated with exposure to certain herbicide agents. DATES: Comments must be received by VA on or before... Siddiqui, Hafeez-U R; Spruce, Michelle; Alty, Stephen R; Dudley, Sandra A large proportion of individuals who live with type-2 diabetes suffer from plantar sensory neuropathy. Regular testing and assessment for the condition is required to avoid ulceration or other damage to patient's feet. Currently accepted practice involves a trained clinician testing a patient's feet manually with a hand-held nylon monofilament probe. The procedure is time consuming, labor intensive, requires special training, is prone to error, and repeatability is difficult. With the vast increase in type-2 diabetes, the number of plantar sensory neuropathy sufferers has already grown to such an extent as to make a traditional manual test problematic. This paper presents the first investigation of a novel approach to automatically identify the pressure points on a given patient's foot for the examination of sensory neuropathy via optical image processing incorporating plantar anthropometry. The method automatically selects suitable test points on the plantar surface that correspond to those repeatedly chosen by a trained podiatrist. The proposed system automatically identifies the specific pressure points at different locations, namely the toe (hallux), metatarsal heads and heel (Calcaneum) areas. The approach is generic and has shown 100% reliability on the available database used. The database consists of Chinese, Asian, African, and Caucasian foot images. Seto, Yoshihiro; Okazaki, Fumiyasu; Horikawa, Keiji; Zhang, Jing; Sasaki, Hitoshi; To, Hideto Although cis-diamminedichloro-platinum (CDDP) exhibits strong therapeutic effects in cancer chemotherapy, its adverse effects such as peripheral neuropathy, nephropathy, and vomiting are dose-limiting factors. Previous studies reported that chronotherapy decreased CDDP-induced nephropathy and vomiting. In the present study, we investigated the influence of dosing times on CDDP-induced peripheral neuropathy in rats. CDDP (4 mg/kg) was administered intravenously at 5:00 or 17:00 every 7 days for 4 weeks to male Sprague-Dawley rats, and saline was given to the control group. To assess the dosing time dependency of peripheral neuropathy, von-Frey test and hot-plate test were performed. In order to estimate hypoalgesia, the hot-plate test was performed in rats administered CDDP weekly for 4 weeks. On day 28, the withdrawal latency to thermal stimulation was significantly prolonged in the 17:00-treated group than in the control and 5:00-treated groups. When the von-Frey test was performed to assess mechanical allodynia, the withdrawal threshold was significantly lower in the 5:00 and 17:00-treated groups than in the control group on day 6 after the first CDDP dose. The 5:00-treated group maintained allodynia throughout the experiment with the repeated administration of CDDP, whereas the 17:00-treated group deteriorated from allodynia to hypoalgesia. It was revealed that the severe of CDDP-induced peripheral neuropathy was inhibited in the 5:00-treated group, whereas CDDP-treated groups exhibited mechanical allodynia. These results suggested that the selection of an optimal dosing time ameliorated CDDP-induced peripheral neuropathy. Garg, Kanwaljeet; Aggarwal, Ankita; Srivastava, Deep Narayan; Jana, Manisha; Sharma, Raju; Gamanagatti, Shivanand; Kumar, Atin; Kumar, Vijay; Malhotra, Rajesh; Goyal, Vinay; Garg, Kanwaljeet Peripheral neuropathies refer to a group of disorders in which there is damage to the nerves of the peripheral nervous system. Electrophysiological studies are the main stay for the diagnosis of peripheral neuropathies. However, direct visualization of the nerves is possible with exact localization of site of pathology with high resolution ultrasonogram and 3 Tesla MRI scanner, and newer MR sequences. We did a cross sectional study including a total of 55 patients and 64 nerves with upper limb peripheral neuropathies. All the included patients underwent high resolution focused ultrasound of the nerves and MR neurography. Nerve Conduction Velocity study was done for reference. The diagnostic confidence of TSE T2W MR sequence was seen to be highest with a sensitivity of 95.31% while it was 81.25% for ultrasonogram. Continuity of the nerve in patients with traumatic neuropathy was seen in 65.7% and 62.86% (22/35) nerves on MRI and ultrasonogram respectively. T1W and T2W MR sequences were seen to be equally effective in establishing the continuity of the nerve. Increase in the calibre/ thickening was seen in 77% of cases on MRI, and 73.8% of cases on USG. Neuroma formation was seen equally on both MR & USG in 60.66%. We consistently found low fractional anisotropy (FA) values at the site of pathology. Ultrasound is a sensitive technique to diagnose peripheral neuropathies and it should be used as a screening modality for a focused MR to be performed later. TSE T2W FS has the highest sensitivity to pick nerve pathology and is comparable to NCS. Amongst the newer sequences, DTI should be done to increase the diagnostic confidence. Copyright © 2017 Elsevier Inc. All rights reserved. Ezendam, Nicole P M; Pijlman, Brenda; Bhugwandass, Celine; Pruijt, Johannes F M; Mols, Floortje; Vos, M Caroline; Pijnenborg, Johanna M A; van de Poll-Franse, Lonneke V This study assessed the prevalence and risk factors of chemotherapy-induced peripheral neuropathy, and its impact on health-related quality of life among ovarian cancer survivors, 2-12 years after diagnosis. Women (n=348) diagnosed with ovarian cancer between 2000 and 2010, as registered by the Dutch population-based Eindhoven Cancer Registry, were eligible for participation. A questionnaire, including the EORTC QLQ-C30 and EORTC QLQ-OV28 measures, containing 3 items about neuropathy, was returned by 191 women (55%). Recurrence and chemotherapy data were obtained from medical records. Of all 191 women, the 129 women who received chemotherapy more often reported having tingling hands/feet and feeling numbness in fingers/toes, specifically 51% reported "a little" to "very much" of these symptoms vs. about 27% who did not receive chemotherapy. Women reporting more neuropathy symptoms reported lower levels of functioning and overall quality of life. They also reported more symptoms of fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, and financial problems. Moreover, women reporting more neuropathy symptoms had experienced the disease and treatment more often as being a burden and were more worried about their health, had more gastrointestinal and hormonal symptoms, hair loss and more other chemotherapy side effects. Linear regression analyses showed that more cycles of chemotherapy, more recurrences and a shorter period since last treatment were associated with a higher neuropathy score. Neuropathy symptoms were experienced by 51% of women with ovarian cancer who received chemotherapy even up to 12 years after the end of treatment, and this seriously affected their HRQoL. Copyright © 2014 Elsevier Inc. All rights reserved. Barreira, A A; Marques Júnior, W Studies on peripheral neuropathies by investigators residing in the State of São Paulo, Brazil, and published since the 1930 and 1940 decades until 1985 were revised in the present survey. Investigations in the area were greatly encouraged by the appearance of the journal Arquivos de Neuro-Psiquiatria(São Paulo). Oswaldo Freitas Julião may be considered the author who began these studies in the State and his most important contributions were related to leprosy and to Andrade disease, although he also published papers on other types of peripheral neuropathies. Horacio Martins Canelas also made a very important contribution to the study of different neuropathies, especially those due to vitamin B12 deficiency. A series of papers on neuropathies published by neurologists residing in the State is summarized. We also present a catalogue of the major university centers where groups of neurologists preferentially devote their time to the study of neuromuscular disease in São Paulo and a selected bibliography about neuropathies by investigators from this State. Allen, D; Riordan-Eva, P; Paterson, R W; Hadden, R D M The syndrome of subacute simultaneous peripheral neuropathy and bilateral optic neuropathy is known to occur in tropical countries, probably due to malnutrition or toxicity, but not often seen in developed countries. We report seven patients in London who were not malnourished or alcoholic, and in whom no clear cause was found. We retrospectively reviewed the case notes and arranged some further investigations. All patients developed peripheral and bilateral optic neuropathy within 6 months. Patients were aged 30-52, and all of Jamaican birth and race but lived in the UK. Most had subacute, painful ataxic sensory axonal neuropathy or neuronopathy, some with myelopathy. Nerve conduction studies revealed minor demyelinating features in two cases. The optic neuropathy was symmetrical, subacute and monophasic, usually with marked reduction in visual acuity. CSF protein concentration was usually elevated but other laboratory investigations were normal. Patients showed only modest improvement at follow-up. These patients share a common clinical and electrophysiological phenotype, age, ethnicity and elevated CSF protein, but otherwise normal laboratory investigations. The syndrome is a cause of significant morbidity in young people. The cause remains uncertain despite thorough investigation. Copyright © 2013 Elsevier B.V. All rights reserved. Bales, Joshua G; Meals, Roy In the orthopedic patient, the diagnosis of a compression neuropathy may be straightforward. However, various medical comorbidities can obscure this diagnosis. It is paramount for the practicing orthopedic surgeon to have an appreciation for the medical pathology of common axonal neuropathies to properly diagnose, treat, and refer a patient with altered sensation in the upper extremity. The prevalence of diabetes in the United States is 10%, and roughly 20% of diabetic patients have peripheral neuropathy. In addition to diabetes, 32% of heavy alcohol users present with polyneuropathy. With advancements in the treatment of human immunodeficiency virus/acquired immunodeficiency syndrome clinicians may see the long-term effects of the virus manifested as axonal neuropathies and extreme allodynia. In some regions of the world, Hansen's disease usurps diabetes as the most common cause of polyneuropathy. Based on patient demographics and social habits, Lyme disease, multiple sclerosis, and syphilis can all manifest as polyneuropathies. Understanding the common medical causes of neuropathy will aid the orthopedic surgeon in differentiating simple compression neuropathies from diseases mimicking or confounding them. Knill-Jones, R. P.; Goodwill, C. J.; Dayan, A. D.; Williams, Roger In a prospective study of 70 unselected patients with chronic liver disease, clinical signs of a peripheral neuropathy were observed in 13 patients. Abnormal nerve conduction was demonstrated in nine of these and in one further patient who had no abnormal neurological signs. The occurrence of a neuropathy (in patients with cryptogenic cirrhosis, haemochromatosis, active chronic hepatitis as well as in alcoholic cirrhosis) could not be related to liver function, although it was associated with higher IgA and IgM values. Clinical diabetes was present in six of the 14 patients with neuropathy but there was no relation in the non-diabetic patients between neuropathy and minor impairment of carbohydrate tolerance. Those with neuropathy had a significantly higher incidence of oesophageal varices and there was also a relationship to a history of previous encephalopathy. Sural nerve biopsy was carried out on 14 patients, eight of whom had clinical or electrodiagnostic evidence of neuropathy. Single nerve fibres were examined by teasing and in all nerves histological evidence was found of an indolent process which had damaged whole Schwann cells and which resulted in demyelination and remyelination. Diabetic angiopathy was not seen and axonal degeneration, which was never severe, was found in all disease groups equally. Images PMID:4337271 Vinik, A I; Casellini, C; Névoret, M-L Here we review some seldom-discussed presentations of diabetic neuropathy, including large fiber dysfunction and peripheral autonomic dysfunction, emphasizing the impact of sympathetic/parasympathetic imbalance. Diabetic neuropathy is the most common complication of diabetes and contributes additional risks in the aging adult. Loss of sensory perception, loss of muscle strength, and ataxia or incoordination lead to a risk of falling that is 17-fold greater in the older diabetic compared to their young nondiabetic counterparts. A fall is accompanied by lacerations, tears, fractures, and worst of all, traumatic brain injury, from which more than 60% do not recover. Autonomic neuropathy has been hailed as the "Prophet of Doom" for good reason. It is conducive to increased risk of myocardial infarction and sudden death. An imbalance in the autonomic nervous system occurs early in the evolution of diabetes, at a stage when active intervention can abrogate the otherwise relentless progression. In addition to hypotension, many newly recognized syndromes can be attributed to cardiac autonomic neuropathy such as orthostatic tachycardia and bradycardia. Ultimately, this constellation of features of neuropathy conspire to impede activities of daily living, especially in the patient with pain, anxiety, depression, and sleep disorders. The resulting reduction in quality of life may worsen prognosis and should be routinely evaluated and addressed. Early neuropathy detection can only be achieved by assessment of both large and small- nerve fibers. New noninvasive sudomotor function technologies may play an increasing role in identifying early peripheral and autonomic neuropathy, allowing rapid intervention and potentially reversal of small-fiber loss. © 2016 Elsevier Inc. All rights reserved. Houlden, H; Reilly, M M; Smith, S To investigate and correlate the frequency and types of pupil abnormalities that are associated with hereditary peripheral neuropathy in a large cohort of patients prospectively examined. A prospective study between 1998 and 2007. Patients were enrolled and examined after being seen in the neurology clinic. Data were collected on demographics, family and medical history. Patients had eye and pupillography testing carried out as well as being neurologically and genetically investigated. A consecutive series of 131 cases of inherited peripheral neuropathy were seen and categorized into five groups: familial amyloid polyneuropathy (FAP), Charcot Marie Tooth disease (CMT), hereditary neuropathywith liability to pressure palsies (HNPP), Refsum's disease, and hereditary sensory and autonomic neuropathy. A number of unreported mutations were identified in these patient groups. Pupil abnormalities were common in the Refsum's group, with frequent abnormally small pupils. The inherited neuropathies commonly associated with autonomic abnormalities were frequently found to have developed bilateral Horner's syndrome, which was particularly prevalent in our FAP series. Abnormalities were rare in HNPP and CMT type 1, but CMT type 2 showed frequent and varied pupil defects. The results describe the pupil abnormalities that were frequently associated with the particular group of inherited neuropathy patients, but we could not predict the genetic defect or the neuropathy severity. This is the first study of the pupil abnormalities found in the inherited neuropathies and provides an overview of the frequency and type of defects seen in a large number of cases. This series along with the detailed tables will act as an important diagnostic aid in assessing these patients. Yu, Shuai; Chen, Ying; Hou, Xu; Xu, Donghua; Che, Kui; Li, Changgui; Yan, Shengli; Wang, Yangang; Wang, Bin Previous studies suggested a possible association between serum uric acid levels and peripheral neuropathy in patients with type 2 diabetes, but no definite evidence was available. A systematic review and meta-analysis of relevant studies were performed to comprehensively estimate the association. Pubmed, Web of Science, Embase, and China Biology Medicine (CBM) databases were searched for eligible studies. Study-specific data were combined using random-effect or fixed-effect models of meta-analysis according to between-study heterogeneity. Twelve studies were finally included into the meta-analysis, which involved a total of 1388 type 2 diabetic patients with peripheral neuropathy and 4746 patients without peripheral neuropathy. Meta-analysis showed that there were obvious increased serum uric acid levels in diabetic patients with peripheral neuropathy (weighted mean difference [WMD] = 50.03 μmol/L, 95% confidence interval [95%CI] 22.14-77.93, P = 0.0004). Hyperuricemia was also significantly associated with increased risk of peripheral neuropathy in patients with type 2 diabetes (risk ratio [RR] = 2.83, 95%CI 2.13-3.76, P < 0.00001). Meta-analysis of two studies with adjusted risk estimates showed that hyperuricemia was independently associated with increased risk of peripheral neuropathy in type 2 diabetic patients (RR = 1.95, 95%CI 1.23-3.11, P = 0.005). Type 2 diabetic patients with peripheral neuropathy have obvious increased serum uric acid levels, and hyperuricemia is associated with increased risk of peripheral neuropathy. Further prospective cohort studies are needed to validate the impact of serum uric acid levels on peripheral neuropathy risk. Lupachyk, Sergey; Watcho, Pierre; Stavniichuk, Roman; Shevalye, Hanna; Obrosova, Irina G. Endoplasmic reticulum stress resulting from abnormal folding of newly synthesized proteins impairs metabolism, transcriptional regulation, and gene expression, and it is a key mechanism of cell injury. Endoplasmic reticulum stress plays an important role in cardiovascular and neurodegenerative diseases, cancer, and diabetes. We evaluated the role for this phenomenon in diabetic peripheral neuropathy. Endoplasmic reticulum stress manifest in upregulation of multiple components of unfolded protein response was identified in neural tissues (sciatic nerve, spinal cord) of streptozotocin diabetic rats and mice. A chemical chaperone, trimethylamine oxide, administered for 12 weeks after induction of diabetes (110 mg⋅kg−1⋅d−1, a prevention paradigm) attenuated endoplasmic reticulum stress, peripheral nerve dysfunction, intraepidermal nerve fiber loss, and sciatic nerve and spinal cord oxidative-nitrative stress in streptozotocin diabetic rats. Similar effects on diabetes-induced endoplasmic reticulum stress and peripheral nerve dysfunction were observed with a structurally unrelated chemical chaperone, 4-phenylbutyric acid (100 mg⋅kg−1⋅d−1, intraperitoneal). CCAAT/enhancer-binding protein homologous protein (CHOP)−/− mice made diabetic with streptozotocin displayed less severe sciatic nerve oxidative-nitrative stress and peripheral neuropathy than the wild-type (C57Bl6/J) mice. Neither chemical chaperones nor CHOP gene deficiency reduced diabetic hyperglycemia. Our findings reveal an important role of endoplasmic reticulum stress in the development of diabetic peripheral neuropathy and identify a potential new therapeutic target. PMID:23364451 Uwah, Augusta N; Ackler, Joan; Leighton, John C; Pomerantz, Sherry; Tester, William Chemotherapy-induced neurotoxicity is a significant source of morbidity for cancer patients. This study aimed to assess the relationship between preexisting diabetes and clinically significant (National Cancer Institute Common Toxicity Criteria grades 2 and 3) OXIPN; between diabetes, and the cumulative dose at onset of OXIPN; and between other preexisting medical conditions and the development of OXIPN. We reviewed medical records of all patients with stage II-IV colon cancer treated in the Albert Einstein Cancer Center, Philadelphia, with oxaliplatin from 2005 to 2009. Exclusion criteria included preexisting neuropathy, previous neurotoxic chemotherapy exposure, and incomplete medical records. The NCI Common Toxicity Criteria was used to grade sensory neuropathy. Univariate analysis was used to estimate odds ratios and confidence limits for prevalence of OXIPN in patients with and without diabetes. The mean level and cumulative doses were compared using the t test. Sixty-two patients met the study criteria; 23 oxaliplatin-treated patients were excluded. The crude incidence of any OXIPN was 65%. There was no relationship found between development of OXIPN and the presence of diabetes, smoking, hypertension, or statin use. However, the mean cumulative dose of oxaliplatin was significantly lower for patients with diabetes who developed neuropathy, compared with those without diabetes (388 vs. 610 mg/m(2); P = .021). Although the presence of diabetes did not appear to affect the severity of OXIPN, patients with diabetes developed OXIPN at a lower cumulative dose of oxaliplatin (P < .05). The results may have implications for treatment of patients with diabetes and colon cancer. Copyright © 2012 Elsevier Inc. All rights reserved. Baker, Steven K; Lipson, David M We report the case of a 46-day-old boy with a fulminant vincristine-induced peripheral neuropathy after treatment for congenital acute lymphoblastic leukemia. Flaccid paralysis developed at the end of the first phase of induction, requiring intubation and ventilation for 51 days. Treatment was initiated with levocarnitine, N-acetylcysteine, and pyridoxine and progressive reversal of the neuropathy occurred over the next 4 months. Potential differences in pathogenesis and presentation of vincristine neurotoxicity and Guillian-Barre syndrome in the neonate are discussed. Oomatia, A; Fang, H; Petri, M; Birnbaum, J To characterize peripheral neuropathy subtypes, ancillary studies, and immunologic profiles associated with peripheral neuropathies in patients with systemic lupus erythematosus (SLE). In this 25-year study of 2,097 SLE patients, we characterized peripheral neuropathies due to SLE and compared clinical and SLE-related features in patients with versus those without neuropathy. The prevalence of peripheral neuropathies was 5.9% (123 of 2,097 patients), and 66.7% of these patients (82 of 123) had peripheral neuropathies attributable to SLE. We noted that 17.1% of the patients with peripheral neuropathies due to SLE (14 of 82 patients) had small-fiber neuropathy, which is a painful neuropathy not included in the American College of Rheumatology (ACR) neuropsychiatric SLE (NPSLE) case definitions. SLE patients with small-fiber neuropathies could present with unorthodox neuropathic pain patterns not consistent with a stocking-glove distribution and had associated skin biopsy results suggestive of dorsal root ganglion neuronal cell loss. Compared to SLE patients without peripheral neuropathies, those with peripheral neuropathies had lower mean disease activity (P = 0.01) and higher disease damage (P < 0.01) and were more likely to have a history of herpes zoster virus infection (P < 0.01), osteoporotic fractures (P < 0.01), and opportunistic infections (P < 0.01). Our findings indicate that small-fiber neuropathy is a frequently occurring peripheral neuropathy. The skin biopsy findings in small-fiber neuropathy patients support the notion that distinct mechanisms target the dorsal root ganglia as well as distal axons. SLE patients with peripheral neuropathy have lower mean disease activity scores and higher disease damage. Our findings suggest that revision of the ACR NPSLE case definitions, which currently do not include small-fiber neuropathies, is warranted. Copyright © 2014 by the American College of Rheumatology. Carlos, Fernando; Espejel, Luis; Novick, Diego; López, Rubén; Flores, Daniel Painful diabetic peripheral neuropathy affects 40-50% of patients with diabetic neuropathy, leading to impaired quality of life and substantial costs. Duloxetine and pregabalin have evidence-based support, and are formally approved for controlling painful diabetic peripheral neuropathy. We used a 12-week decision model for examining painful diabetic peripheral neuropathy first-line therapy with daily doses of duloxetine 60mg or pregabalin 300mg, under the perspective of the Instituto Venezolano de los Seguros Sociales. We gathered model parameters from published literature and expert´s opinion, focusing on the magnitude of pain relief, the presence of adverse events, the possibility of withdrawal owing to intolerable adverse events or due to lack of efficacy, and the quality-adjusted life years expected in each strategy. We analyzed direct medical costs (which are expressed in Bolívares Fuertes, BsF) comprising drug acquisition besides additional care devoted to treatment of adverse events and poor pain relief. We conducted both deterministic and probabilistic sensitivity analyses. Total expected costs per 1000 patients were BsF 1 046 146 (26%) lower with duloxetine than with pregabalin. Most of these savings (91%) corresponds to the difference in the acquisitions cost of each medication. duloxetine also provided 23 more patients achieving good pain relief and a gain of about two quality-adjusted life years per 1000 treated. Model was robust to plausible changes in main parameters. Duloxetine remained the preferred option in 93.9% of the second-order Monte Carlo simulations. This study suggests duloxetine dominates (i.e., is more effective and lead to gains in quality-adjusted life years), remaining less costly than pregabalin for treatment of painful diabetic peripheral neuropathy. CG, Shashi Kumar; Hande, H Manjunath; Vidyasagar, Sudha; Rao, Karthik; Rajagopal, K.V Background & aims: Diabetic peripheral neuropathy (DPN) accounts for most common complications of T2DM. Painful DPN is associated with functional limitation & poor quality of life. Therefore, objective of the study is to find the effect of low level laser therapy on painful diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM) Materials & methods: The study design is pre-post observational design. After obtaining ethical clearance and informed consent, 19 T2DM subjects were screened and confirmed for peripheral neuropathy in an outpatient setting with biochemical parameter, pain scale and Michigan Neuropathy Screening Instrument (MNSI). Low Level Laser therapy was irradiated through scanning mode with dosage of 3.1J/cm2 on the plantar and dorsum of the foot and 3.4j/cm2 with contact method for 10days and all subjects were reassessed at the end of the 10 day. Descriptive statistics and paired′ test was used to analyze the pre-post finding within the group. Level of significance was set at p<0.05 Results: The result analysis showed significant reduction in Pain using VAS scale (6.47 ± 0.84 to 1.21 ± 0.78 (p<0.001), MNSI (5.52 ± 1.26 to 2.71 ± 0.97 (reduction in Vibration perception threshold (32.68 ± 6.08 to 24.84 ± 4.29 (<0.001) and a significant increase in the temperature from baseline to post intervention (30.01 ± 2.11 to 31.75 ± 1.03 (p<0. 001). Conclusion: In the present study, Low level laser therapy was found to be effective in type 2 DM with peripheral neuropathy. PMID:26557734 Fallah, Alireza; Mirzaei, Alireza; Gutknecht, Norbert; Demneh, Amir Saberi Peripheral sensory neuropathy treatment is one of the common treatment problems and causes morbidity and mortality in people suffering from that. Although treatment depends on the underlying cause of the condition, nevertheless, in some cases, there is no cure for it, and it requires palliative and symptomatic treatment. In laboratory studies, low-level laser has been effective in the nerves protection and restoration. The aim of this article is to investigate the clinical efficacy of low-level laser on improvement of the peripheral somatosensory neuropathy. Search in the articles published up to 30 October 2015 (full text and abstracts) in databases PubMed (Medline), Cochrane library, Physiotherapy Evidence Database was performed. The studies of low-level laser trials on patients with peripheral neuropathy were carried out and evaluated in terms of the exclusion criteria. There are 35 articles among which 10 articles had the intended and required criteria. 1, 3, and 6 articles study the patients with diabetes, neuropathy caused by trauma, and carpal tunnel syndrome, respectively. In six studies, laser led to a reduction in sensory impairment and improvement of the physiological function of the sensory nerves. In these articles, lasers (Diode, GaAlAs, He-Ne) had wavelength range 660-860 nm, radiation power 20-250 mW, energy density 0.45-70 J/cm(2). The intervention sessions range was 6-21 times and patient follow-up was 0-6 months. According to the results of these studies, low-level laser therapy can improve sensory function in patients with peripheral somatosensory neuropathy, although little research have not been done, laser treatment regimens are varied and do not recommend a specific treatment protocol. It seems it requires more research to sum up better, particularly in relation to diabetes. Lauria, G; Cornblath, D R; Johansson, O; McArthur, J C; Mellgren, S I; Nolano, M; Rosenberg, N; Sommer, C Skin biopsy has become a widely used tool to investigate small calibre sensory nerves including somatic unmyelinated intraepidermal nerve fibres (IENF), dermal myelinated nerve fibres, and autonomic nerve fibres in peripheral neuropathies and other conditions. Different techniques for tissue processing and nerve fibre evaluation have been used. In March 2004, a Task Force was set up under the auspices of the European Federation of Neurological Societies (EFNS) with the aim of developing guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathies. We searched the Medline database from 1989, the year of the first publication describing the innervation of human skin using immunostaining with anti-protein-gene-product 9.5 (PGP 9.5) antibodies, to 31 March 2005. All pertinent papers were rated according to the EFNS guidance. The final version of the guidelines was elaborated after consensus amongst members of the Task Force was reached. For diagnostic purposes in peripheral neuropathies, we recommend performing a 3-mm punch skin biopsy at the distal leg and quantifying the linear density of IENF in at least three 50-mum thick sections per biopsy, fixed in 2% PLP or Zamboni's solution, by bright-field immunohistochemistry or immunofluorescence with anti-PGP 9.5 antibodies (level A recommendation). Quantification of IENF density closely correlated with warm and heat-pain threshold, and appeared more sensitive than sensory nerve conduction study and sural nerve biopsy in diagnosing small-fibre sensory neuropathy. Diagnostic efficiency and predictive values of this technique were very high (level A recommendation). Confocal microscopy may be particularly useful to investigate myelinated nerve fibres, dermal receptors and dermal annex innervation. In future, the diagnostic yield of dermal myelinated nerve fibre quantification and of sweat gland innervation should be addressed. Longitudinal studies of IENF density and regeneration rate are warranted to In this communication, I first show some points we should mind in the conventional peripheral nerve conduction studies and later present clinical usefulness of motor root stimulation for peripheral neuropathy. CONVENTIONAL NERVE CONDUCTION STUDIES (NCS): The most important point revealed by the conventional NCSs is whether neuropathy is due to axonal degeneration or demyelinating process. Precise clinical examination with this neurophysiological information leads us to a diagnosis and treatment. Poor clinical examination makes these findings useless. Long standing axonal degeneration sometimes induces secondary demyelination at the most distal part of involved nerves. On the other hand, severe segmental demyelination often provokes secondary axonal degeneration at distal parts to the site of demyelination. These secondary changes show the same abnormal neurophysiological findings as those of the primary involvement. We should be careful of this possibility when interpreting the results of NCS. NCS of sensory nerves is not good at revealing demyelinating process. Mild temporal dispersion of potentials often reduces an amplitude of SNAP or loss of responses, which usually suggests axonal degeneration, because of short duration of sensory nerve potentials. MOTOR ROOT STIMULATION IN PERIPHERAL NEUROPATHY: Magnetic stimulation with a coil placed over the spine activates motor roots and evokes EMG responses from upper and lower limb muscles. The site of activation with this method was determined to be where the motor roots exit from the spinal canal (intervertebral foramina) (J Neurol Neurosurg Psychiatry 52 (9): 1025-1032, 1989) because induced currents are very dense at such a foramen made by electric resistant bones. In several kinds of peripheral neuropathy, this method has been used to detect a lesion at a proximal part of the peripheral nerves which can not be detected by the conventional NCSs. I present a few cases in whom motor root stimulation had a clinical Ducic, Ivica; Taylor, Nathan S; Dellon, A Lee This was an initial exploratory study to determine if decompression of the 4 medial ankle tunnels (neurolysis of the tibial, medial and lateral plantar, and calcaneal nerves) could lead to improved foot sensibility, increased proprioception and balance, and decreased falls in a population of patients with impaired lower extremity sensation. Fourteen patients with peripheral neuropathy were included in this study. Seventy-one percent of patients were females. Average age was 67 years. All patients were evaluated preoperatively and postoperatively to assess their lower extremity sensibility, as well as their ability to stand still, maintaining their balance with their eyes open and then closed, which is defined as "sway." Lower extremity sensibility was measured with the Pressure-Specified Sensory Device (PSSD), which evaluates 1- and 2-point discrimination for the pulp of the big toe and medial heel. The MatScan Measurement System measured each patient's sway. Neuropathy was the result of diabetes in 72% of patients, a combination of diabetes and hypothyroidism in 7%, chemotherapy in 7%, and idiopathic in 14%. Eight patients underwent peripheral nerve decompression on 1 lower extremity, whereas 6 patients underwent bilateral lower extremity peripheral nerve decompression. Mean toe and heel sensibility improved 9% and 7%, respectively, in the unilateral group, whereas the bilateral group experienced an improvement in mean toe and heel sensibility of 42% (P = 0.02) and 32%, respectively. Preoperative and postoperative sway comparison in the unilateral group revealed a reduction in sway with eyes open and eyes closed by 5% and 31%, respectively. Comparison of preoperative and postoperative sway in the bilateral group showed a reduction with eyes open and eyes closed by 23% and 145% (P = 0.05), respectively. This initial study suggests that there may be benefit from bilateral lower extremity peripheral nerve decompression in helping improve pedal sensibility and balance Salazar-Leal, Martha E; Flores, M S; Sepulveda-Saavedra, Julio; Romero-Diaz, Viktor J; Becerra-Verdin, Eduardo M; Tamez-Rodriguez, Victor A; Martinez, Hector R; Piñeyro-Lopez, Alfredo; Bermudez, M V Intoxication by Karwinskia humboldtiana (buckthorn) fruit presents a neurological picture similar to that of Guillain-Barré syndrome. In this report, we describe an experimental animal model of peripheral neuropathy induced by buckthorn fruit. Four groups of Wistar rats received one oral dose of 1.5 g/kg followed by oral doses of 0.5 g/kg at days 3, 7, 10, and 14 of dried and ground buckthorn fruit in aqueous suspension. Rats were sacrificed at 24, 48, 58, and 112 days after initial dose. Treated animals developed progressive paralysis through 58 days, then completely recovered by 112 days. Sciatic nerves showed segmental demyelination and cellular infiltrates until 58 days after exposure and then remyelinating changes at 112 days. This experimental model for peripheral neuropathy is reproducible and easy to handle. Its manipulation is relatively innocuous and allows us to study reversible peripheral nerve damage. This model can be developed in other animal species and may be useful to test new therapies for peripheral neuropathy. Nam, Soo Hyun; Hong, Young Bin; Hyun, Young Se; Nam, Da Eun; Kwak, Geon; Hwang, Sun Hee; Choi, Byung-Ok; Chung, Ki Wha Inherited peripheral neuropathies (IPN), which are a group of clinically and genetically heterogeneous peripheral nerve disorders including Charcot-Marie-Tooth disease (CMT), exhibit progressive degeneration of muscles in the extremities and loss of sensory function. Over 70 genes have been reported as genetic causatives and the number is still growing. We prepared a targeted gene panel for IPN diagnosis based on next generation sequencing (NGS). The gene panel was designed to detect mutations in 73 genes reported to be genetic causes of IPN or related peripheral neuropathies, and to detect duplication of the chromosome 17p12 region, the major genetic cause of CMT1A. We applied the gene panel to 115 samples from 63 non-CMT1A families, and isolated 15 pathogenic or likely-pathogenic mutations in eight genes from 25 patients (17 families). Of them, eight mutations were unreported variants. Of particular interest, this study revealed several very rare mutations in the SPTLC2, DCTN1, and MARS genes. In addition, the effectiveness of the detection of CMT1A was confirmed by comparing five 17p12-nonduplicated controls and 15 CMT1A cases. In conclusion, we developed a gene panel for one step genetic diagnosis of IPN. It seems that its time- and cost-effectiveness are superior to previous tiered-genetic diagnosis algorithms, and it could be applied as a genetic diagnostic system for inherited peripheral neuropathies. Li, Qing-rong; Wang, Zhuo; Zhou, Wei; Fan, Shou-rui; Ma, Run; Xue, Li; Yang, Lu; Li, Ya-shan; Tan, Hong-li; Shao, Qing-hua; Yang, Hong-ying Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by suppressing the expression of aldose reductase in peripheral nerves of diabetes mellitus rats. The high-fat and high-carbohydrate model rats were established by intraperitoneal injection of streptozotocin. Peripheral neuropathy occurred in these rats after sustaining high blood glucose for 8 weeks. At 12 weeks after streptozotocin injection, rats were intragastrically administered epalrestat 100 mg/kg daily for 6 weeks. Transmission electron microscope revealed that the injuries to myelinated nerve fibers, non-myelinated nerve fibers and Schwann cells of rat sciatic nerves had reduced compared to rats without epalrestat administuation. Western blot assay and immunohistochemical results demonstrated that after intervention with epalrestat, the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase gradually increased, but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway. PMID:27073391 Nam, Soo Hyun; Hong, Young Bin; Hyun, Young Se; Nam, Da Eun; Kwak, Geon; Hwang, Sun Hee; Choi, Byung-Ok; Chung, Ki Wha Inherited peripheral neuropathies (IPN), which are a group of clinically and genetically heterogeneous peripheral nerve disorders including Charcot-Marie-Tooth disease (CMT), exhibit progressive degeneration of muscles in the extremities and loss of sensory function. Over 70 genes have been reported as genetic causatives and the number is still growing. We prepared a targeted gene panel for IPN diagnosis based on next generation sequencing (NGS). The gene panel was designed to detect mutations in 73 genes reported to be genetic causes of IPN or related peripheral neuropathies, and to detect duplication of the chromosome 17p12 region, the major genetic cause of CMT1A. We applied the gene panel to 115 samples from 63 non-CMT1A families, and isolated 15 pathogenic or likely-pathogenic mutations in eight genes from 25 patients (17 families). Of them, eight mutations were unreported variants. Of particular interest, this study revealed several very rare mutations in the SPTLC2, DCTN1, and MARS genes. In addition, the effectiveness of the detection of CMT1A was confirmed by comparing five 17p12-nonduplicated controls and 15 CMT1A cases. In conclusion, we developed a gene panel for one step genetic diagnosis of IPN. It seems that its time- and cost-effectiveness are superior to previous tiered-genetic diagnosis algorithms, and it could be applied as a genetic diagnostic system for inherited peripheral neuropathies. PMID:27025386 Yoon, Hang Seob; Choi, Woo Jin; Sung, Il Hoon; Lee, Ho Seong; Chung, Hyung Jin Background This study evaluated the effects of Beraprost sodium (Berasil) on subjective leg symptoms in patients with peripheral arterial disease caused by diabetes mellitus. Methods Ninety-four diabetic patients with peripheral arterial disease were treated with Beraprost in a fixed-dose, prospective, multicenter, cohort study. Beraprost (40 µg) was administered orally 3 times daily (120 µg/day) for 12 weeks. We developed a new disease-specific symptom questionnaire, which evaluated the effect of peripheral arterial disease on leg discomfort in daily life and assessed therapeutic responses to treatment. Patients were asked for their subjective assessment of symptoms on a written questionnaire before treatment and after 12 weeks of therapy. Results There was significant improvement in all estimated subjective symptoms (burning, coldness, edema, exertional pain, stabbing, and paresthesias) in the lower extremities at 12 weeks (p < 0.001). There were 18 patients with neuropathy in whom significant improvement was noted for 6 subjective symptoms at 12 weeks (p < 0.05). Adverse events considered to be drug-related were observed in 4 patients (4.3%), all of which were mild and resolved with discontinuation of the medication. Conclusions Beraprost is effective as a treatment for improving various subjective symptoms in the lower extremities, such as burning, coldness, edema, exertional pain, stabbing, and paresthesias, in diabetic patients with peripheral arterial disease. PMID:23730480 Lechleitner, Monika; Abrahamian, Heidemarie; Francesconi, Claudia; Kofler, Markus These are the guidelines for diagnosis and treatment of diabetic neuropathy. This diabetic late complication comprises a number of mono- and polyneuropathies, plexopathies, radiculopathies and autonomic neuropathy. The position statement summarizes characteristic clinical symptoms and techniques for diagnostic assessment of diabetic neuropathy. Recommendations for the therapeutic management of diabetic neuropathy, especially for the control of pain in sensorimotor neuropathy, are provided. Male Breast Cancer; Neurotoxicity; Peripheral Neuropathy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer Cettomai, Deanna; Kwasa, Judith K.; Birbeck, Gretchen L.; Price, Richard W.; Cohen, Craig R.; Bukusi, Elizabeth A.; (OB/Gyn), MMed; Kendi, Caroline; Meyer, Ana-Claire L. INTRODUCTION Peripheral neuropathy is the most common neurological complication of HIV but is widely under-diagnosed in resource-limited settings. We investigated the utility of screening tools administered by non-physician health care workers (HCW) and quantitative sensory testing (QST) administered by trained individuals for identification of moderate/severe neuropathy. METHODS We enrolled 240 HIV-infected outpatients using two-stage cluster randomized sampling. HCWs administered the several screening tools. Trained study staff performed QST. Tools were validated against a clinical diagnosis of neuropathy. RESULTS Participants were 65% women, mean age 36.4 years, median CD4 324 cells/μL. 65% were taking antiretrovirals, and 18% had moderate/severe neuropathy. The screening tests were 76% sensitive in diagnosing moderate/severe neuropathy with negative predictive values of 84–92%. QST was less sensitive but more specific. DISCUSSION Screening tests administered by HCW have excellent negative predictive values and are promising tools for scale-up in resource-limited settings. QST shows promise for research use. PMID:24037693 Goldberg, Allon; Russell, James William; Alexander, Neil Burton Type 2 diabetes mellitus (T2DM) and pre-diabetes or impaired glucose tolerance (IGT) affect a large segment of the population. Peripheral neuropathy (PN) is a common complication of T2DM, leading to sensory and motor deficits. While T2DM-related PN often results in balance- and mobility-related dysfunction which manifests as gait instability and falls, little is known about balance capabilities in patients who have evidence of PN related to IGT (IGT-PN). We evaluated patients with IGT-PN on commonly-used clinical balance and mobility tests as well as a new test of trunk position sense and balance impairment, trunk repositioning errors (TREs). Eight participants aged 50-72 years with IGT-PN, and eight age- and gender-matched controls underwent balance, mobility and trunk repositioning accuracy tests at a university neurology clinic and mobility research laboratory. Compared to controls, IGT-PN participants had as much as twice the magnitude of TREs and stood approximately half as long on the single leg balance test. People with IGT-PN exhibit deficits in standing balance and trunk position sense. Furthermore, there was a significant association between performance on commonly-used clinical balance and mobility tests, and electrophysiological and clinical measures of neuropathy in IGT-PN participants. Because IGT-related neuropathy represents the earliest stage of diabetic neuropathy, deficits in IGT-PN participants highlight the importance of early screening in the dysglycemic process for neuropathy and associated balance deficits. Handsaker, J C; Brown, S J; Bowling, F L; Marple-Horvat, D E; Boulton, A J M; Reeves, N D To examine the stepping accuracy of people with diabetes and diabetic peripheral neuropathy. Fourteen patients with diabetic peripheral neuropathy (DPN), 12 patients with diabetes but no neuropathy (D) and 10 healthy non-diabetic control participants (C). Accuracy of stepping was measured whilst the participants walked along a walkway consisting of 18 stepping targets. Preliminary data on visual gaze characteristics were also captured in a subset of participants (diabetic peripheral neuropathy group: n = 4; diabetes-alone group: n = 4; and control group: n = 4) during the same task. Patients in the diabetic peripheral neuropathy group, and patients in the diabetes-alone group were significantly less accurate at stepping on targets than were control subjects (P < 0.05). Preliminary visual gaze analysis identified that patients diabetic peripheral neuropathy were slower to look between targets, resulting in less time being spent looking at a target before foot-target contact. Impaired motor control is theorized to be a major factor underlying the changes in stepping accuracy, and potentially altered visual gaze behaviour may also play a role. Reduced stepping accuracy may indicate a decreased ability to control the placement of the lower limbs, leading to patients with neuropathy potentially being less able to avoid observed obstacles during walking. © 2015 Diabetes UK. Loprinzi, Paul D; Hager, Kathy K; Ramulu, Pradeep Y To determine if physical activity and/or blood glycohemoglobin (HbA1c) are associated with the prevalence of peripheral neuropathy (PN) in a representative population of diabetics. Three hundred thirty-nine diabetic participants (40-85 yrs) taking part in 2003-2004 National Health and Nutrition Examination Survey were studied. Participants were defined as having peripheral neuropathy if examination determined ≥1 insensate area in either foot. Moderate-to-vigorous physical activity (MVPA) was objectively-measured using accelerometry. After adjustments, MVPA was not significantly associated with PN (OR=1.16; 95% CI: 0.48-2.78), nor was HbA1c (OR=0.55; 95% CI: 0.28-1.04). However, there was evidence of statistical interaction (OR=0.24; 95% CI: 0.06-0.87) between MVPA and HbA1c status, showing that diabetics engaging in higher levels of MVPA and having normal HgbA1c levels were less likely to have PN than what would be expected based on the individual effects of MVPA and HbA1c alone. Although MVPA was not directly associated with PN, these findings suggest that proper physical activity, coupled with good glycemic control, is associated with less neuropathy. Future longitudinal studies are required to evaluate whether physical activity and improved glycemic control may help prevent or slow the progression of diabetic end-organ damage, particularly diabetic neuropathy. Kallianpur, Asha R; Hulgan, Todd Peripheral neuropathy is an important complication of antiretroviral therapy. Nucleoside reverse-transcriptase inhibitor (NRTI)-associated mitochondrial dysfunction, inflammation and nutritional factors are implicated in its pathogenesis. Pharmacogenetic and genomic studies investigating NRTI neurotoxicity have only recently become possible via the linkage of HIV clinical studies to large DNA repositories. Preliminary case–control studies using these resources suggest that host mitochondrial DNA haplogroup polymorphisms in the hemochromatosis gene and proinflammatory cytokine genes may influence the risk of peripheral neuropathy during antiretroviral therapy. These putative risk factors await confirmation in other HIV-infected populations but they have strong biological plausibility. Work to identify underlying mechanisms for these associations is ongoing. Large-scale studies incorporating clearly defined and validated methods of neuropathy assessment and the use of novel laboratory models of NRTI-associated neuropathy to clarify its pathophysiology are now needed. Such investigations may facilitate the development of more effective strategies to predict, prevent and ameliorate this debilitating treatment toxicity in diverse clinical settings. PMID:19374518 Kim, Eun Sook; Lee, Sung Won; Mo, Eun Young; Moon, Sung Dae; Han, Je Ho Several studies have suggested that bilirubin, a potent innate antioxidant, plays a protective role against cardiovascular and microvascular disease. This study investigated the association between serum concentrations of total bilirubin (TB) and the presence of diabetic peripheral neuropathy (DPN) in Korean diabetic patients. This cross-sectional study involved 1207 patients aged more than 30 years with type 2 diabetes. DPN was assessed according to clinical symptoms and physical examinations using Michigan Neuropathy Screening Instrument examination score, 10-g monofilament sensation, and current perception threshold. The subjects were stratified into gender-specific tertiles based on TB values, and the relationship between the TB values and DPN was analyzed. Compared with patients within the lowest TB tertile, those with higher TB levels consisted of patients with shorter duration of diabetes, lower HbA1c, better renal function, and less autonomic neuropathy, retinopathy, and albuminuria. Serum TB levels were inversely associated with DPN. In multivariate analysis for the development of DPN after adjusting for potential confounding factors including retinopathy, albuminuria, and autonomic neuropathy, the TB levels were inversely associated with the presence of DPN, both as a continuous variable [odds ratio (OR) per log standard deviation (SD) 0.79; 95% confidence interval (CI) 0.65-0.97; P = 0.022] and when categorized in tertiles (the highest vs. the lowest tertile; OR 0.63; 95% CI 0.40-0.99; P = 0.046). Low serum bilirubin levels are significantly associated with DPN, independently of classic risk factors and other microvascular complications. Further investigation is necessary to determine whether serum bilirubin has a prognostic significance on DPN. Investigate the association of peripheral autonomic neuropathy (PAN) symptoms and sympathetic skin response (SSR) in the patients with diabetic polyneuropathy (DPN) as a pilot study in Thai patients. Sixty-eight DPN patients' limbs, conducted retrospectively between June 2012 and January 2014, were included and divided into two groups, 48 abnormal SSR limbs and 20 control limbs, respectively. All clinical data, demographic characteristics, PAN symptoms, and other associated factors were compared and analyzed. A comparison between abnormal and normal SSR groups in DPN limbs showed no significant differences of age, gender, body mass index (BMI), comorbidity of hypertension and dyslipidemia, duration of PAN symptoms, associated neurological signs of impaired light touch sensation, and muscle weakness or atrophy (p-value > 0.05). The PAN symptoms, either anhidrosis or hypohidrosis, and hyporemia showed significantly correlated to abnormal SSRs (p-value = 0.003 and 0.028, respectively). Among symptoms of somatic small fiber neuropathy (SFN), burning paresthesia, and reduced thermal sensation revealed significantly correlated to abnormal SSRs (p-value = 0.032 and 0.021, respectively). Moreover, the study showed that history of fall in six months, history of foot ulcer in three months, impaired pinprick sensation, im	2	176	4	0	1	27	0.553842	32	137,355
Epilepsy is a malfunction of the brain. It is triggered by nerve cells that suddenly simultaneously fire impulses and discharge themselves electrically. ICD codes for epilepsy: G40 \| G41 • Description: Epilepsy is characterized by epileptic seizures. These are short-term functional disorders of the brain in which nerve cells are electrically discharged in an extreme form. • Types: There are different types of seizures and forms of epilepsy, for example generalized seizures (such as absences or “grand mal”), focal seizures, rolandic epilepsy, Lennox-Gastaut syndrome, West syndrome, etc. • Causes: partly unknown, partly due to another disease (brain damage or inflammation of the epidermis, concussion, stroke, diabetes, etc.). Very often, the combination of genetic predisposition and another disease leads to the development of epilepsy, experts believe. • Treatment: usually with medication (antiepileptics). If these don’t work well enough, sometimes surgery or electrical stimulation of the nervous system (such as vagus nerve stimulation) are treatments. What is epilepsy? Epilepsy (“falling sickness”) is one of the most common temporary functional disorders of the brain. It is characterized by epileptic seizures: nerve cells (neurons) in the brain suddenly fire synchronously and uncontrolled impulses for a short time. Such an attack can vary in severity. The effects are correspondingly variable. For example, some patients only feel a slight twitching or tingling of individual muscles. Others are briefly “out of the way” (absent). In the worst case, there is an uncontrolled seizure of the whole body and a brief loss of consciousness. According to the International League Against Epilepsy (ILAE), epilepsy is diagnosed when: • At least two epileptic seizures occur more than 24 hours apart. Most often, these seizures come “out of nowhere” (unprovoked seizures). On the other hand, in rarer forms of epilepsy, triggers for the seizures can be identified, such as light stimuli, noise or warm water (reflex seizures). • While only one unprovoked or reflex seizure occurs, there is at least a 60 percent chance of having more seizures in the next ten years. It is therefore just as great as the general risk of recurrence after two unprovoked seizures. • There is a so-called epilepsy syndrome, for example the Lennox-Gastaut syndrome (LGS). Epilepsy syndromes are diagnosed on the basis of certain findings that include, for example, the type of seizure, electrical brain activity (EEG), the result of imaging tests and the age of onset. So-called occasional seizures must be distinguished from this “real” epilepsy. These are individual epileptic seizures that can occur in the course of various diseases. As soon as the acute illness subsides, these occasional cramps also stop. An example of this is febrile seizures: these epileptic seizures occur in connection with fever, especially in young children. However, there is no evidence of a brain infection or any other specific cause. In addition, occasional cramps can occur, for example, with severe circulatory disorders, poisoning (with medication, heavy metals), inflammation (such as meningitis), concussion or metabolic disorders. Types of epilepsy There are many different types and characteristics of epilepsy. The classifications in the specialist literature vary, however. A commonly used (rough) classification is as follows: • Generalized epilepsies and epilepsy syndromes: Here the seizures cover the entire brain. Depending on the type of seizure, generalized seizures are further divided into, for example, tonic seizures (limbs cramp and stiffen), clonic seizures (slow jerking of large muscle groups), or tonic-clonic (“grand mal”) seizures. • Focal epilepsies and epilepsy syndromes: Here the seizures are limited to a limited area of the brain. The symptoms of the seizure depend on its function. For example, twitching of the arm (motor seizure) or changes in vision (visual seizure) are possible. In addition, epilepsy can begin focally, but then spread to the entire brain. This is how it develops into a generalized seizure. In addition to these two large groups of epilepsies, there are also seizures of unclear onset and unclassifiable epileptic seizures. During an epileptic seizure, either the whole brain (generalized seizure) or a specific area of the brain (focal seizure) suddenly becomes overactive. The whole thing often only takes a few seconds, sometimes a little longer. As a rule, however, an epileptic seizure is over after two minutes at the latest. An epileptic seizure is very often followed by an after-phase: although the brain cells are no longer pathologically electrically discharged, abnormalities can still appear for up to several hours. These include, for example, a disturbance in attention, speech disorders, memory disorders or aggressive states. However, sometimes people recover completely after an epileptic seizure after just a few minutes. An epileptic seizure can be disturbing to outsiders. In most cases, however, it is not dangerous and ends on its own within a few minutes. If you witness an epileptic seizure, you should follow the following rules to help the patient: - Keep Calm! - Don’t leave the patient alone, calm him down! - Protect the patient from injury! - Do not hold the patient! Epilepsy in children Epilepsy very often occurs in childhood or adolescence. It is one of the most common diseases of the central nervous system in this age group. In Germany and other industrialized countries, around 50 out of 100,000 children develop epilepsy every year. Taking medication regularly can usually prevent further epileptic seizures in young patients. A healthy lifestyle is also important: If the epileptic seizures are “triggered” by certain triggers (such as lack of sleep, flickering lights, certain noises, etc.), these should be avoided as far as possible. Overall, epilepsy in children is easily treatable in many cases. And the concern of many parents that epilepsy could impair their child’s development is mostly unfounded. Symptoms of epilepsy The exact symptoms of epilepsy depend on the form of the disease and the severity of the epileptic seizures. For example, the mildest variant of a generalized seizure consists only in a short-term mental “absence” (absence): the patient has “gone away” briefly. At the other end of the scale is the “big seizure” (grand mal): First, the whole body cramps and stiffens (tonic phase). Then he begins to twitch uncontrollably (clonic phase). During such a tonic-clonic seizure, patients are unconscious. Another severe type of epilepsy is the so-called “status epilepticus” : This is an epileptic seizure that lasts longer than five minutes. Sometimes there is a series of seizures in rapid succession without the patient regaining full consciousness in between. Such situations are emergencies that must be treated as quickly as possible by the emergency doctor! Cause and risk factors of epilepsy The development of epilepsy is diverse and complex. The exact development of the disease often remains in the dark. In some cases, despite modern examination methods, no specific cause can be identified for epileptic seizures, although there are clear indications of a cause in the brain. Then one speaks of unexplained (cryptogenic) epilepsy. Sometimes it is not even possible to explain why a patient has epileptic seizures. There is no evidence of the cause, such as pathological changes in the brain or metabolic disorders. This is what doctors call idiopathic epilepsy. Recently, however, this term has been (at least partially) replaced by ” genetic epilepsy “: Many sufferers probably or demonstrably have genetic changes, for example at binding sites (receptors) for neurotransmitters. According to experts, such genetic changes can contribute to the development of epilepsy. It is therefore usually not hereditary. Parents usually only pass on the susceptibility to seizures to their children. The disease only occurs when external factors come into play (such as sleep deprivation or hormonal changes). Finally, with regard to the causes, there is another group of epilepsies: In many patients, structural changes in the brain or underlying diseases can be identified as the cause of the epileptic seizures. Doctors refer to this as symptomatic epilepsy or – according to more recent proposals – as structural/metabolic epilepsy. This includes, for example, epileptic seizures that are based on congenital malformations of the brain or brain damage acquired at birth. Also craniocerebral trauma, brain tumors, stroke, inflammation of the brain (encephalitis) or the meninges (Meningitis) and metabolic disorders (diabetes, thyroid diseases, etc.) are among the possible causes of epilepsy. Sometimes epilepsy is both genetic and structural/metabolic. For example, in some people with a genetic susceptibility to epileptic seizures, epilepsy is only triggered by a stroke, meningitis, poisoning or another specific disease. Diagnosis of epilepsy Anyone who experiences an epileptic seizure for the first time should be examined by a doctor. This can determine whether it is actually epilepsy or whether the seizure has other reasons. The first point of contact is usually the family doctor. If necessary, he will refer the patient to a specialist in nerve diseases (neurologist). The first step on the way to diagnosing “epilepsy” is taking the medical history (anamnesis): To do this, the doctor talks to the patient (if old enough) and accompanying persons (such as parents, partners) in detail. He allows the epileptic seizure to be described in detail. Here it is an advantage if people are present during the conversation who have had the seizure are present during the conversation. The person concerned often cannot remember it well. Based on the descriptions, the doctor can assess the seizure pattern (seizure anamnesis). Sometimes there are photos or video recordings of the epileptic seizure. They can be very helpful to the doctor, especially when the focus is on the patient’s face. The eyes are important seizure symptoms and help distinguish an epileptic seizure from other seizures. During the conversation, the doctor also asks about possible triggers of the seizure (such as flickering lights), possible underlying diseases and known cases of epilepsy in the family. The interview is followed by a physical examination. The state of the nervous system is also checked using various tests and examinations (neurological examination). This includes one measuring the brain waves (electroencephalography, EEG): Sometimes epilepsy can be recognized by typical curve changes in the EEG. However, the EEG in epilepsy can also be unremarkable. Magnetic resonance imaging (MRI or magnetic resonance imaging) is very important in the clarification of an epileptic seizure. Detailed cross-sectional images of the brain are created. The doctor can then identify any damage or malformations of the brain as a possible cause of the seizure. In addition to the MRI, a computed tomography of the skull is sometimes made. Computer tomography can be used especially in the acute phase (shortly after the attack). can help to discover, for example, cerebral hemorrhage as the cause of the attack. Laboratory tests can provide clarity if brain inflammation (encephalitis) or another underlying disease is suspected as the cause of the epileptic seizure. A blood test can provide indications of inflammation or metabolic changes. If the doctor suspects drug use as the cause of the seizure, appropriate blood tests are done. The doctor can also use a fine hollow needle to take a sample of the cerebrospinal fluid from the spinal canal (liquor or lumbar puncture). The analysis in the laboratory helps, for example, brain or meningitis (encephalitis, meningitis) or a brain tumor detect or rule out. In individual cases, further examinations may be necessary, for example to rule out other types of seizures or to clarify the suspicion of certain underlying diseases. Treatment of epilepsy The long-term treatment of epilepsy patients is usually carried out by a registered neurologist or child and adolescent neurologist. Sometimes it can also make sense to go to an outpatient facility or clinic that specializes in epilepsy treatment (specialist practice for epilepsy, epilepsy outpatient clinic, epilepsy center). This applies, for example, if the diagnosis is unclear, epileptic seizures occur despite treatment, or special problems are related to epilepsy. Epilepsy: therapy is not always necessary Has anyone (so far) only had one epileptic seizure, treatment can often be delayed. In some cases, it is sufficient if patients avoid known triggers (such as loud music, flickering lights, computer games) and adopt a healthy lifestyle. These include, among other things, a regular lifestyle, regular and sufficient sleep and not drinking alcohol. In addition, patients should be particularly cautious in situations where a sudden seizure could have dire consequences. This applies, for example, to extreme sports, scaffolding work and when handling heavy machinery. If possible, epileptics should avoid such situations. In structural/metabolic epilepsy, the doctor first treats the underlying disease (meningitis, diabetes, liver disease, etc.). Here, too, patients should avoid all factors that can trigger an epileptic seizure. Sometimes, however, treatment with epilepsy medication is advisable even after a single seizure. This may be the case, for example, if the patient has a high risk of further seizures. Drug therapy should also begin immediately in the case of very specific forms of epilepsy (such as Lennox-Gastaut syndrome, temporal lobe epilepsy, etc.). In general, doctors recommend epilepsy treatment after the second seizure at the latest. In general, however, it always depends on the situation of the individual patient when and how epilepsy is treated. For example, some patients only have an epileptic seizure every few years. Others have more frequent seizures, which they perceive as less stressful (e.g. only short “pauses” = absences). Then the doctor will carefully weigh up the benefits and risks of epilepsy treatment. In doing so, he also takes into account how willing the patient is to follow medical recommendations (adherence to therapy). There is little point in prescribing medication if the patient does not (regularly) take it after all. Drug treatment helps most people with epilepsy to lead a seizure-free life. So-called antiepileptic drugs are used. They inhibit the excessive activity of nerve cells in the brain. This can reduce the risk of a seizure. That is why they are also called anticonvulsants (= anticonvulsants). However, the drugs cannot do anything against the cause of epilepsy. This means: antiepileptic drugs only have a symptomatic effect, but cannot cure epilepsy. Various active ingredients are used as antiepileptics, for example levetiracetam or valproic acid. The doctor will select an active ingredient for each patient that is likely to work best in the specific case. The type of seizures or the form of the epilepsy plays an important role. In addition, the doctor takes possible side effects into account when choosing the antiepileptic drug and its dosage. The goal is for the treatment to prevent (or at least reduce the number of) future seizures. At the same time, the drug should cause no or only tolerable side effects. As a rule, the doctor prescribes only one antiepileptic drug (monotherapy) for epilepsy. If this drug does not have the desired effect or causes severe side effects, the doctor may try switching the patient to another drug. Sometimes several preparations have to be tried out before the individually “best” antiepileptic is found. In some patients, epilepsy cannot be adequately controlled with monotherapy. Then the doctor can prescribe two (or more) antiepileptic drugs. Such combination therapy is carefully planned and monitored. In general, the more different medications someone takes, the more likely it is that undesirable interactions can occur. The risk of side effects may also increase. The epilepsy medications are often taken as tablets, capsules or juice. Some can also be given as an injection, IV, or suppository. Antiepileptic drugs can only help if they are used regularly. It is therefore very important to follow the doctor’s instructions exactly! How long do you have to use antiepileptic drugs? Antiepileptic drugs are usually taken for several years. If, thanks to treatment, no more epileptic seizures have occurred for a long time, patients can sometimes try to stop taking the drug after talking to their doctor. But this must not happen suddenly. Instead, the dosage should be reduced gradually as recommended by the doctor. In some patients, the epileptic seizures then return (sometimes only after months or years). Then the epilepsy medication must be taken again. Other patients remain permanently seizure-free even after stopping antiseizure drugs. This can happen, for example, if the cause of the seizures (such as meningitis = meningitis) has now healed. This cannot be predicted in individual cases. The attending doctor can only estimate the risk of seizures without medication based on the individual situation of the patient. In some cases, epileptics have to be prepared from the start that they will probably need the medication for life – for example if permanent brain damage is the cause of the epilepsy. Never stop taking your epilepsy medication on your own – it can be life-threatening! In some patients, epilepsy cannot be adequately treated with medication. If the seizures always start in a limited region of the brain (focal seizures), this part of the brain can be surgically removed (resection, resective surgery). This can in many cases prevent future epileptic seizures. However, resective surgery is only possible under certain conditions. It must be relatively safe to cut out the relevant brain region. In addition, it must not entail any unacceptable disadvantages for the patient, such as a serious impairment of certain brain functions. Resective brain surgery is performed primarily in patients in whom the epileptic seizures originate in the temporal lobe of the brain. More rarely, other surgical procedures are performed in severe epilepsy. This can be the case, for example, with patients who frequently experience severe seizure attacks – i.e. epileptic seizures in which they fall in a flash and may seriously injure themselves. A so-called bar severing (callosotomy) can be considered here: The surgeon cuts through the so-called bar (corpus callosum) in the brain completely or partially. This is the link between the right and left hemispheres of the brain. This intervention can significantly reduce the number of falls. However, there is a risk of cognitive impairment as a side effect. Therefore, the benefits and risks of callosotomy must be carefully weighed against each other. In addition to an operation, so-called stimulation procedures can also be considered if medication for epilepsy is not effective enough. Certain structures in the brain or those that lead there (vagus nerve) are stimulated with a low current. This can help against epileptic seizures. There are a number of different methods that can be used to treat epilepsy. The most common is vagus nerve stimulation (VNS) : A small, battery-operated device is implanted under the patient’s skin below the left collarbone. It is a type of pacemaker that connects to the left vagus nerve in the neck via a wire that also runs under the skin. At intervals (for example, every five minutes for 30 seconds), it delivers gentle shocks of electricity to the nerve. This can significantly reduce the frequency of epileptic seizures. In some patients, however, it takes a few months for this effect to set in. During the current pulses, some patients experience hoarseness, coughing or abnormal sensations (“buzzing” in the body). Vagus nerve stimulation can also have a positive effect on co-existing depression. Another stimulation method is deep brain stimulation : Small electrodes are implanted in the patient at certain points in the brain. They stimulate the nerve tissue with electrical impulses. As a result, the number of seizures decreases in many patients. Possible side effects include depression and memory problems. Deep brain stimulation should only be performed in specialized centers. Treatment for status epilepticus If someone suffers status epilepticus, bystanders should immediately call the emergency doctor – there is a risk of death! The patient is first given a sedative (benzodiazepine). It can also be administered by laypersons if the epileptic is carrying the emergency medication with them: it is either placed in the cheek (buccal tablet) or inserted as a cream into the patient’s anus via a small tube. The emergency doctor who arrives can also administer the sedative as an injection into a vein. He then rushes the patient to a hospital. The treatment will continue there. If the status epilepticus still cannot be ended after 30 to 60 minutes, many patients are given anesthesia and artificial respiration. Course and prognosis of epilepsy The course and prognosis of epilepsy depend on the type of seizure and the type of epilepsy. There are also differences from patient to patient. In general, about half of the patients have a single epileptic seizure. The other half will have another seizure sooner or later. After that, the risk of seizures continues to rise: about seven out of ten patients who have already had two attacks have another epileptic seizure within a year. People whose epilepsy is caused by an underlying disease such as a brain disease are particularly at risk: The risk of further seizures is about twice as high in them as in patients whose epilepsy is based on a genetic predisposition or has no known cause. With the right and consistent treatment, further epileptic seizures can be avoided in most cases. But patients can do more to prevent seizures. Many of those affected benefit from sufficient sleep with regular sleep times (sleep hygiene). Sometimes epileptic seizures are provoked by certain triggers. Then patients should avoid them as much as possible. But that only works if you know the triggers. A seizure calendar can help here: the patient notes the day, time and type of each individual seizure along with the current medication intake. Accompanying circumstances and possible triggers are also recorded, for example computer work, loud music, alcohol consumption, sleep deprivation, emotional stress or the sight of certain optical patterns (such as a checkerboard pattern). This helps doctor and patient to identify the trigger factors. Living with epilepsy If epilepsy is well controlled with treatment, you as a patient can lead a largely normal life. However, you should take a few precautions to avoid dangerous situations: - Do not use electric knives or slicers. - Avoid bathing and take a shower instead. Also, never go swimming unaccompanied. Death by drowning is about 20 times more common in epileptics than in the general population! - Always ride your bike with a helmet and prefer routes with little traffic. - Choose a low bed (risk of falling). - Secure sharp edges in the home. - Keep a safe distance from roads and bodies of water. - Don’t lock yourself in. Use a “busy” sign in the restroom instead. - Don’t smoke in bed! Whether you, as an epilepsy patient, are allowed to get or keep your driving license depends on whether you are fit to drive. Ask your neurologist for advice on this. He or she can best assess how high your risk of seizures is. Epilepsy patients who get behind the wheel even though they are unfit to drive endanger themselves and others! They also risk their insurance coverage. Most jobs and sports are generally also possible for epileptics – especially if, thanks to therapy, epileptic seizures no longer occur. In individual cases, the doctor treating you is best able to assess whether the patient should avoid a certain activity or sport. He may also be able to recommend special precautions. Epilepsy: contraception & desire to have children Some epilepsy medications reduce the effectiveness of birth control pills. Conversely, the pill can also impair the effectiveness of some antiepileptic drugs. Girls and women with epilepsy should discuss such interactions with their doctor. He may recommend another contraceptive. If women with epilepsy want to have children, they should definitely discuss this with their neurologist – preferably before they become pregnant. The drug treatment for epilepsy may have to be adjusted during pregnancy. In higher doses, antiepileptic drugs can disrupt the development of the child or cause birth defects (up to the 12th week of pregnancy). This risk is also higher with combination therapy (several antiepileptic drugs) than with monotherapy (treatment with a single antiepileptic drug). The doctor will take this into account when planning the therapy. A special feature also applies to folic acid preparations, which are recommended to all women during pregnancy: some antiepileptic drugs lower the folic acid level in the body. Therefore, epileptics should possibly take folic acid in higher doses. If an epileptic seizure occurs during pregnancy, there is usually no particular reason for concern: the seizure usually does not harm the unborn child – unless it is a long-lasting, generalized seizure, or the expectant mother is seriously injured. But that only happens very rarely. In general, seizures are not very common during pregnancy : around two-thirds of all epileptics remain seizure-free for the entire nine months. In addition, most women with epilepsy give birth to healthy children. Epilepsy awareness month Epilepsy is a neurological disorder that affects 3 million Americans and nearly 65 million people worldwide. Those spontaneous seizures that affect people of all ages are the hallmark of epilepsy. In the United States, November is National Epilepsy Awareness Month.	2	7	0	0	0	2	0.89345	2	5,417
Macrophage: large mononuclear phagocyte. This cell may be called a histiocyte in the tissues; it is called a monocyte in the blood. An antigen must come in contact with or pass through a macrophage before it can become a processed antigen with the ability to encounter the then sensitize a small lymphocyte. Macrophage-Activating Factor: sensitized T lymphocytes can release a non-specific macrophage-activating factor that creates a cytotoxic population of macrophages that appear to distinguish malignant from normal cells, killing only malignant ones. Macrorestriction Map: map depicting the order of and distance between sites at which restriction enzymes cleave chromosomes. Major Histocompatibility Complex (MHC): a cluster of genes encoding cell surface molecules that are polymorphic within a species and that code for antigens, which leads to rapid graft rejection between members of a single species that differ at these loci. Several classes of protein, such as MHC class I and class II proteins, are encoded in this region. Malformation: also congenital anomaly or birth defect. Any defect present at birth, probably of developmental origin. Managed Care: the use of a "manager" to control utilization of medical services and control costs. Managed Competition: government regulation of a health care market which uses competition as the means to achieve efficiency objectives within a framework of government intervention designed to achieve other policy objectives, such as equity. Management: the measures taken to plan, organize, operate and evaluate all the many elements of a system and the personnel involved. Manual Vacuum Aspiration (MVA): a technique for evacuating the contents of the uterus through use of a specially designed hand-held syringe. Mapping: see -- gene mapping, linkage map, physical map. Mapping Population: the group of related organisms used in constructing a genetic map. Marginal Benefit: the additional benefit obtained by consuming the last (or next) unit of a commodity. Marker: see -- genetic marker. Market Failure: the situation in which a market economy fails to attain economic efficiency. Market Mechanism: the interaction of buyers and sellers in market and mixed economies which determines the nature and volume of goods and services produced and their distribution. Mass Spectrometry: an instrument used to identify chemicals in a substance by their mass and charge. Maternal Mortality Ratio, Reported: the quotient between the number of maternal deaths in a given year and the number of live births in that same year, expressed by 100,000 live births, for a given country, territory, or geographic area, as reported from the national health authority. Maternal death is defined as the death of a woman while pregnant or within the 42 days after termination of that pregnancy, regardless of the length and site of the pregnancy, due to any cause related to or aggravated by the pregnancy itself or its care but not due to accidental or incidental causes. Mean: the average of a sample of observations. Mean Value: the average of a set of numbers. In epidemiology, the sample mean is the average value of the observations in a sample. Meatus: opening to the urethra. Median: the middle value when the values are arranged in order from the smallest to the largest. Median Value: the median is a number that separates the upper 50% of a sample from the lower 50%. It is the middle value of a distribution. Medical Eligibility Criteria: criteria for a woman's eligibility to use a contraceptive method, based on the relative health risks and benefits of using such a method for a woman with a given condition. Medical Savings Account: allows or mandates people to place money in (tax-free) savings accounts to be used only for medical expenses, usually in conjunction with the purchase of a catastrophic stop-loss health insurance plan. Megabase (Mb): unit of length for DNA fragments equal to 1 million nucleotides and roughly equal to 1 cM. See also -- centimorgan. Meiosis: the process of two consecutive cell divisions in the diploid progenitors of sex cells. Meiosis results in four rather than two daughter cells, each with a haploid set of chromosomes. See also -- mitosis. Memory Cells: cells that can mount an accelerated antibody response to antigen. Mendelian Inheritance: one method in which genetic traits are passed from parents to offspring. Named for Gregor Mendel, who first studied and recognized the existence of genes and this method of inheritance. See also -- autosomal dominant, recessive gene, sex-linked. Messenger RNA (mRNA): RNA that serves as a template for protein synthesis. The mature form of processed RNA used as a template for directing translation of proteins. See also -- genetic code. Meta-analysis: an amalgamation of studies -- a complex task to avoid misleading conclusions. The goal of combining results from different sources is to delineate which features are universal. The quality of the studies included is important to the final result. Many think that only prospective randomized clinical trials should be combined for a meta-analysis because such trials are usually of the highest quality. Metaphase: a stage in mitosis or meiosis during which the chromosomes are aligned along the equatorial plane of the cell. Methylation: (see DNA Methylation). MeV: 1,000,000 eV. MHC Restriction: the ability of T lymphocytes to respond only when they are presented with the appropriate antigen to which in association with either self MHC class I or class II molecules. Microarray: sets of miniaturized chemical reaction areas that may also be used to test DNA fragments, antibodies, or proteins. Microbial Genetics: the study of genes and gene function in bacteria, archaea, and other microorganisms. Often used in research in the fields of bioremediation, alternative energy, and disease prevention. See also -- model organisms, biotechnology, bioremediation. Microinjection: a technique for introducing a solution of DNA into a cell using a fine microcapillary pipet. Microinjection (of Sperm): injection of one or more sperm under the outer covering of the oocyte for fertilization. Micronuclei: chromosome fragments that are not incorporated into the nucleus at cell division. Micturition: another term for urination or voiding. Migration Inhibition Factor: a lymphokine produced when a sensitized lymphocyte is exposed to an antigen to which it is sensitized. Migration inhibition factor inhibits the migration of these lymphocytes. Milking: checking for penile discharge by placing the fingers of one hand several centimeters behind the scrotum and bringing them upward and forward towards the base of the penis. Minimum Data Set (MDS): federally mandated screening and assessment form for Medicare- and Medicaid-certified long-term care facilities in the United States. This form is completed within 14 days of admission to the facility, quarterly, and when there is a significant change in the resident's status. An annual update is also required. The information collected in the MDS is used in planning the care of the individual. Minor Histocompatibility Antigens: these antigens, encoded outside the MHC, are numerous but do not generate rapid graft rejection or primary responses of T cells in vitro. They do not serve as restricting elements in cell interactions. Missense: a mutation that alters a codon so that it encodes a different amino acid. Mitochondrial DNA: the genetic material found in mitochondria, the organelles that generate energy for the cell. Not inherited in the same fashion as nucleic DNA. See also cell, DNA, genome, nucleus. Mitochondrial Inheritance: mitochondria are inherited exclusively from women. Because they contain DNA, mitochondrial inheritance allows transmission of genes directly from the woman to her offspring. Mitogen: a substance that induces immunocompetent lymphocytes to undergo blast transformation, mitosis, and cell division (causing mitosis or cell division). Mitosis: the process of nuclear division in cells that produces daughter cells that are genetically identical to each other and to the parent cell. See also -- meiosis. Mixed Formulae: often payment of professionals is based on a mix of methods (i.e. capitation plus fee-for-service for some services). Similarly, systems can be supplemented by bonus/target payments as an incentive for achieving certain objectives. Mixed Urinary Incontinence: combination of involuntary leakage associated with urgency and also with exertion, effort, sneezing, and coughing. A person has both urge and stress urinary incontinence. Mobilization: one of three sub-functions in the financing of health systems which aims at identifying and getting the money required to meet the health needs of the people, individually and collectively, in a given health system. Models: simplified descriptions of processes or systems. Model Organisms: a laboratory animal or other organism useful for research. Modeling: the use of statistical analysis, computer analysis, or model organisms to predict outcomes of research. Molecular Biology: the study of the structure, function, and makeup of biologically important molecules. Molecular Farming: the development of transgenic animals to produce human proteins for medical use. Molecular Genetics: the study of macromolecules important in biological inheritance. Molecular Medicine: the treatment of injury or disease at the molecular level. Examples include the use of DNA-based diagnostic tests or medicine derived from DNA sequence information. Monitoring: the ongoing process of collecting and analyzing information about the implementation of the activity such as newborn resuscitation. Monitoring and Evaluation: monitoring is the process of keeping track of events. For example, the monitoring of a project may involve counting the number of people coming into contact with it over a period of time or recording the way in which the project is administered and developed. Evaluation involves making a judgment as to how successful (or otherwise) a project has been, with success commonly being measured as the extent to which the project has met its original objectives. Both the "process" (activities) and "outcomes" (what is produced, for example in terms of changes in the health of those targeted by the project) can be monitored and evaluated. Monoclonal Antibody: antibodies with such high intrinsic specificity that only one or two antigenic determinants are recognized. Monogenic Disorder: a disorder caused by mutation of a single gene. See also -- mutation, polygenic disorder. Monogenic Inheritance: see -- monogenic disorder. Monokines: soluble substances, secreted by monocytes, that have a variety of effects on other cells. Monosomy: possessing only one copy of a particular chromosome instead of the normal two copies. See also -- cell, chromosome, gene expression, trisomy. Moral Hazard: The possibility of consumers or providers exploiting a benefit system unduly to the detriment or disadvantage of other consumers, providers or the financing community as a whole, without having to bear the financial consequences or their behavior in part or in full. Morbidity: a state of disease. Morbid Map: a diagram showing the chromosomal location of genes associated with disease. Morula: a compact sphere of 16 blastomeres that forms at about 3-4 days after fertilization. Morbidity Rate: illness or disability rate, usually expressed per 1000 population. Mortality Rate: death rate per defined population, usually expressed per 1000. Mortality Rate from Land Transport Accidents, Estimated: the estimated total number deaths from land transport accidents, in the total population or of a given sex and/or age, divided by the total number of this population, expressed per 100,000 population, for a given year, in a given country, territory, or geographic area. Underlying causes of death grouped under this heading are those ICD-10 codes V01-V89. Mortality Rate from Motor Vehicle Traffic Accidents, Estimated: the estimated total number deaths from motor vehicle traffic accidents, in the total population or of a given sex and/or age, divided by the total number of this population, expressed per 100,000 population, for a given year, in a given country, territory, or geographic area. Underlying causes of death grouped under this heading are those under ICD-9 codes E810-E819 or ICD-10 codes V02-V04(.1-.9), V09.2,V09.3,V12-V14(.3-.6), V19(.4-.6),V20-V28(.3-.9), V29-V78(.4-.9),V80(.3-.5), V81.1,V82.1,V83-V86(.0-.3), V87(.0-.8),V89.2,V89.9. Mosaic: an individual composed of two or more genetically dissimilar cell lines but from the same species. This can come about by somatic mutation or by grafting cells between individuals of close genetic constitution, such as dizygotic twins. Mosaicism: the presence of two or more populations of cells with different characteristics within one tissue or organ. Mother-To-Child Transmission (MTCT): transmission of HIV from an infected mother to her infant during pregnancy, labor or after delivery through breast milk. Mouse Model: see -- model organisms. Multicenter Trial: a single trial conducted according to a single protocol but at more than one site (from ICH E6). These sites may be across multiple countries. They are advantageous because they offer more rapid patient accrual and allow for greater protocol complexity. Multicenter trials reduce the opportunity for an individual's bias to influence the conduct of the trial; they increase the likelihood for the inclusion of a more representative study population and facilitate a higher standard for data processing and analysis. Multidisciplinary: HIA is not the preserve of any one disciplinary group. Instead, it draws on the experience and expertise of a wide range of "stakeholders", who are involved throughout the process. These may include professionals with knowledge relevant to the issues being addressed, key decision makers, relevant voluntary organizations and -- perhaps most importantly -- representatives of the communities whose lives will be affected by the policy (Barnes and Scott-Samuel, 1999). Multifactorial Inheritance: inheritance of traits that are determined by a combination of genetic and environmental factors. Multifactorial or Multigenic Disorder: see -- polygenic disorder. Multiplexing: a laboratory approach that performs multiple sets of reactions in parallel (simultaneously); greatly increasing speed and throughput. Multistage Sampling: a multistage sample is an extension of a cluster sample, where the initial clusters are broken into further smaller clusters. Once a final selection of clusters to sample is made, a proportion of the subjects within each cluster is sampled. (e.g. if the sampling frame was an entire country then the country would be broken down into regions, then these regions would be broken down into cities and towns and then these would be randomly sampled). Multivariate Analysis: a technique of analysis of data that factors many variables. A mathematical model is constructed that simultaneously determines the effect of one variable while evaluating the effect of other factors that may have an influence on the variable being tested. The two most common algorithms developed to accomplish this task are the step-up and stop-down procedure. Variables are added to an initial small set or deleted from an initial large set while testing repeatedly to see which new factor makes a statistical contribution to the overall model. Murine: organism in the genus Mus. A rat or mouse. Mutagen: an agent that causes a permanent genetic change in a cell. Does not include changes occurring during normal genetic recombination. Mutagenicity: the capacity of a chemical or physical agent to cause permanent genetic alterations. See also -- somatic cell genetic mutation. Mutation: an alteration of DNA sequencing in a gene those results in a heritable change in protein structure or function that frequently has adverse effects. Any heritable change in DNA sequence. See also -- polymorphism. Myc Proto-Oncogenes: the proto-oncogene family that includes c-myc, N-myc, L-myc, and R-myc. They encode nuclear-associated DNA-binding proteins that affect DNA replication and transcription. Dedicated to Women's and Children's Well-being and Health Care Worldwide	2	5	0	0	0	4	0.833473	4	3,470
- Definition and Meaning of Cavitary Lung Lesion - Causes of Cavitary Lung Lesion - Symptoms of Cavitary Lung Lesion - Diagnosis of Cavitary Lung Lesion - Treatment of Cavitary Lung Lesion - ICD 10 - Know More about Cavitary Lung Lesion - Topics in Lung Health A-L The pulmonary cavity is a gas-filled region of the lung that can be seen clinically using conventional computed tomography (CT scan) and chest radiography at the center of a nodule or an area of consolidation. Cavities can be seen in both non-infectious and infectious processes. This article thus gives a brief idea of what cavitary lung lesion is and what are its causes, symptoms, and diagnosis and treatment process. The purpose is to give an overview of the illnesses that are most typically linked with lung cavities, with a focus on epidemiology and clinical features. Definition and Meaning of Cavitary Lung Lesion Lung lesions are already concerning in and of themselves. Cavitating lung lesions are another illustration of the myriad forms of lesions that may afflict the lungs as if their sheer presence isn’t enough to keep people on their toes. The creation of cavities or hollow sections of the lesions gave the cavitating lung lesion its name. Cavitating lung lesions are distinct in that they frequently occur in locations where cystic lung lesions are present. In reality, specialists believe that hollowness is the consequence of the cavity’s fluid or mucus being emptied. Cavitating lung lesions are exceedingly tiny, measuring about 4mm in thickness on average. Lung Cavity, as we know, is a gas-filled space where the thickness of the wall is > 4mm. But when a cyst occurs, the diameter typically becomes < 1 cm. Some most important characteristics of the thin-walled cavitary lesion in the lung include: - It may either be single or multiple. - The distribution of lung lesions. - Progression of the disease. - Rim enhancement and wall thickness reduce more. Causes of Cavitary Lung Lesion Cavitary lung lesions can be caused by the following seral families of microorganisms: - Bacteria (such as Streptococcus pyogenes, Klebsiella pyogenes, Staph.aureus, and Haemophilus influenza) - Typical and atypical Mycobacterium - Fungi (such as pneumocystis and aspergillosis) Lung lesions can have a variety of causes and symptoms which are like: - Bacterial infection has been linked to the development of cavitary lung lesions. This is the most typical reason for the illness. - As a result of too much smoking habit or chemical misuse, it is commonly understood in medical circles that these two addictions are two of the most prevalent causes of cavitating lung lesions. Symptoms of Cavitary Lung Lesion - Coughing is common in persons who have cavitating lung lesions. - Even if there is a discharge of phlegm, it is often clean and free from any bloodstain. - Other signs and symptoms of the disorder include chest congestion, trouble breathing, and, in rare cases, itching in the lungs. - It is also likely that in certain cases with cavitating lung lesions, continuous and intense coughing is the sole evidence that the infection is present. Diagnosis of Cavitary Lung Lesion Cavitary lesions in the lungs are a common imaging funding with a broad differential diagnosis that encompasses malignancies, infections/inflammatory processes, as well as traumatic and congenital lung abnormalities. Cavitary pulmonary nodules can be caused by a variety of disorders. Acute and chronic infections along with chronic systemic disorders and cancers are all a part of the disease spectrum. Choosing the most likely or right diagnosis might be difficult. To establish the proper diagnosis and prescribe the appropriate follow-up or move forward, knowledge of frequent and rare radiological abnormalities in conjunction with pertinent clinical history and findings is required. Infectious Causes – Diagnosis It is critical to ascertain whether the source of a cavitary lung lesion is an infectious condition during the initial assessment. Necrotizing pneumonia and lung abscess, TB, and septic emboli are all considered infectious etiologies. Night sweats, fever, chill, and cough are the very recognized symptoms that last for more than 1 month and are all components of the clinical presentation, as are concomitant illnesses, drug or alcohol addiction, and history of immunocompromise. Due to public health concerns and therapeutic implications, the relation between the cavitary lesion and tuberculosis needs to be covered in its category. The illness must be examined early in the examination of a cavitary lung lesion because TB patients necessitate airborne isolation. Weight loss, hemoptysis, fevers, and night sweats are common symptoms in patients with tuberculosis. Immunocompromised states, incarceration, travel to endemic areas raise the risk of contracting tuberculosis. If TB is detected in a patient, airborne isolation should be started very once. When risk indicators are present, the provider should acquire 3 sputum samples for an acid-fast bacillus (AFB) smear and culture. In most cases patient who has the problem of reactivation TB, have abnormal chest X-rays with air-fluid levels around 20% and this then turns to upper lobe cavitary lesion. Patients with primary or reactivation tuberculosis may develop three cavities. Necrotizing pneumonia and lung abscess Lung abscesses are cavities in the lungs that are accompanied by necrosis from a microbial infection. Although both necrotizing pneumonia and lung abscess indicate a comparable pathophysiologic procedure and are on the same continuum, the term necrotizing pneumonia is often used when there are many smaller related lung abscesses. When there are underlying risk factors for aspiration and poor dentition, a lung abscess is always suspected. If the patient has risk indicators, empiric therapy should include active antibiotics against anaerobes and MRSA for cavitary lesions. Serial chest imaging should be used to monitor the resolution f pulmonary abscesses. Depending on the location of the abscess and local experience with endobronchial or transthoracic drainage and surgical resection, thoracic surgery, interventional surgery should be consulted if the lung abscess does not get resolved. Cavitary lung lesions are more commonly caused by septic emboli. Patients with a history of drug IV usage or contamination in dwelling devices should be evaluated for this condition. An evaluation for symptoms of endocarditis and an inspection for affected indwelling devices should be part of the physical examination. Non-infectious Causes –Diagnosis Non-infectious etiologies must be considered once a cavitary lung lesion is identified. Malignancy, pulmonary embolism, rheumatologic disorders, and other reasons are non-infectious etiologies. The presence of some constitutional symptoms like smoking history, fevers, night sweats, weight loss, and an otherwise full examination of systems are important aspects of the clinical presentation. The most prevalent non-infectious cause of cavitary lung lesions is considered to be a malignancy. It warrants a high index of suspicion because it is often the first diagnosis that is done to consider overall. Primary lung malignancies, lung tumors such as lymphoma, or metastatic illness can all cause cavities. Cavitation has been found in 7 to 11 percent of initial lung malignancies on plain radiography and 22 percent on computed tomography. Rheumatologic illnesses are less prevalent causes of cavitary lesions. According to one study, cavitary lung nodules are seen in 37 percent of individuals with granulomatosis polyangiitis. Cavitary nodules are also observed in rheumatoid arthritis and sarcoidosis, however, they are rare. Because patients with rheumatologic illnesses are frequently treated with immunosuppressive drugs, the infection must always be considered. Pulmonary embolism (PE) Pulmonary embolism can cause infarction and the creation of a cavitary lesion, even though it is commonly overlooked in the examination of cavitary lung lesions. In as much as one-third of PE patients, pulmonary infarction has been documented. On the other hand, chronic thromboembolic illness has also been linked to cavitary lesions. Bronchitis obliterans with organizing pneumonia, amyloidosis, and Langerhans cell histiocytosis are some of the less prevalent causes of cavitary lesions. If the diagnosis remains ambiguous after the initial diagnostic assessment, then the hospitalist should preserve a broad differential and confer with experts. Treatment of Cavitary Lung Lesion - Depending on the patient’s fever and productive cough in combination with recent travel and location of the cavitary lesion, if there is a risk for tuberculosis and endemic fungi then the patient has to be placed on respiratory isolation with AFBs. - A chest CT is to be to evaluate the cavitary mass within the lobes that contained an air-fluid level indicating lung abscess. - The patient can be treated empirically with clindamycin giving a high prevalence of anaerobes in lung abscesses. - A chest x-ray can be done to monitor the effectiveness of antibiotic treatment and to evaluate the persistence of the cavitation. Evaluating the clinical manifestation and predisposing factors, separating infectious causes from the non-infectious ones, and then using this knowledge to further lead the diagnostic examination is the best method for a patient with a cavitary lung lesion. If the cause remains unclear after the first examination, then consultation with further tests such as biopsy can be explored. The ICD-10-CM with code J98.4 is used to describe diseases or terminology such as acquired bulla of the lung, bronchogenic cyst, cavitation of the lung, calcification of the lung, chronic lung illness owing to surfactant problem, chronic lung disease, and so on. This diagnosis code refers to solitary pulmonary nodule where: - R91.1 is a specific/billable ICD-10-CM code that may be used to identify a diagnosis to get compensation. - This version of ICD-AC-CM R91.1 came into effect on October 1, 2021. - This ICD-10-CM code version may differ from country to country. - This code is applicable to coin lesion lung and a solitary pulmonary nodule on the bronchial tree’s sub-segmental branch. The following codes above R91.1 include some back-references that may be relevant to R91.1: - R00-R99 refers to symptoms, and unusual clinical and laboratory results that have not been categorized elsewhere, - R90-R94 refers to abnormal results on diagnostic imaging and function studies without a diagnosis. Know More about Cavitary Lung Lesion While learning more about cavitary lung lesion, some of the main terms that need focus are explained below: Cavitary lesions and tuberculosis Cavitary lesions and tuberculosis are a myriad of fungal, bacterial, and parasitic organisms that lead to cavitary lung disease. Mycobacterium tuberculosis is the most well-known causal pathogen among them. Although the prevalence of tuberculosis has been declining it remains a serious hazard to the immunocompromised population in many countries. Those with poor means and limited healthcare access, intravenous drug users, persons living or working in high-risk residential areas, correctional facilities are also vulnerable to opportunistic organisms. Primary tuberculosis and post-primary tuberculosis are the two types of tuberculosis. The primary TB features include effusion, pulmonary consolidation, and lymphadenopathy. Cavitary lung lesion differential diagnosis Cavitary lung lesion differential diagnosis is extensive, and it may be divided into non-infectious and infectious etiologies. Rheumatologic, malignant, and other less prevalent etiologies, such as pulmonary embolism-related infarct, are non-infectious causes. On the other hand, fungal, bacterial, and parasitic agents are considered to be a part of infectious causes. Cavitary lesion lung cancer Cavitary lesion lung cancer is most common in persons with a long history of smoking in their sixth to seventh decades of life. Unfortunately, cavitation is linked to a grim prognosis in primary lung cancer. Squamous cell carcinoma is the most prevalent kind of primary lung cancer associated with cavitary lesions. Small cell carcinoma is seldom linked with cavitary lesions. The inner walls that are thick and irregular are connected with primary lung cancer. The size of the cavity ranges from 1 to 10cm. Most cavitary lesions with a wall thickness of more than 15mm were malignant, and those between 4-15 mm had mixed results. Multiple cavitary lung lesions Multiple cavitary lung lesions have a wide range of differential diagnoses, including infectious illnesses like fungal infections, TB, and parasite infections, as well as non-infectious disorders like rheumatic and malignant lesions. A pulmonary abscess, a malignant tumor, or a lung cyst is all common causes of a solitary cavitary lung lesion. Wegener’s granulomatosis, metastatic illness, or septic emboli are all possible causes of multiple cavitary lung lesions. In a bronchogenic carcinoma, the inner lining is generally nodular. Upper lobe cavitary lesion Upper lobe cavitary lesion favors tuberculosis where the inner wall may either be smooth or an irregular inner wall. Histoplasmosis can cause cavities in the upper loves with pleural thickening. Blastomycosis and Coccidiomycosis are fungal infections that cause lung infiltrates that can lead to cavitary lesions. Bilateral cavitary lung lesions Bilateral cavitary lung lesions or multiple bilateral masses with cavitation can be seen in inflammatory disorders such as granulomatosis with polyangiitis and rheumatoid arthritis. Rheumatoid nodules can be single or numerous, and they can also cavitate. Squamous cell carcinoma is the best prevalent kind of lung cancer, and it can cause solitary lung lesions in roughly 10-15 percent of cases. Thin-walled cavitary lesion in the lung The thin-walled cavitary lesion in the lung refers to <2mm. In solitary illness, the thickness of the wall of cavitary lung lesions helps in distinguishing between malignant and benign conditions. Recent studies have portrayed that a wall thickness of less than 7mm is specific highly for benign illness, whereas a thickness that is more than 24mm is specific for malignant disease. Fungal cavitary lung lesion Fungal cavitary lung lesion occurs due to pulmonary fungal infections that vary hugely depending upon the patient’s immune condition. Fungal infections are very uncommon especially in immunocompetent patients; however, cavitation from a fungal infection is not uncommon and can even mimic a malignant cavity. As a result, distinguishing a fungal cavity from a malignant cavity might be difficult at times. Topics in Lung Health A-L - Acute Respiratory Failure with Hypoxia - Calcified Granuloma of Lungs – Meaning, causes, Treatment and More - Cavitary Lung Lesion – Definition, Causes, Symptoms, Diagnosis, Treatment, and More - Cavitary Pneumonia - Chronic Bronchitis – Signs, Causes, Treatment and More - Coal Miner Lung Disease (Black Lung Cancer) - Collapsed Lung – Definition, Causes, Symptoms, Diagnosis, Treatment, Surgery, and Recovery - Common Lung Problems - Diffuse Parenchymal Lung Disease - Evali Lung Disease - Foods That Cause Breathing Problems - Ground Glass Nodule - Horizontal Fissure of the Lungs - Increasing Lung Capacity - Lady Windermere Syndrome – Symptoms, Treatment, Prognosis, Life Expectancy and More - Lobectomy – VATS, RATS, Sleeve and More - Lung Biopsy - Lung Damage – Causes, Symptoms, Treatment and Per Cent Stages - Lung Health Supplements - Lung Inflammation – Meaning, Causes, Symptoms, Treatment and More - Lung Pain - Lung Parenchymal Disease	4	7	0	0	0	7	0.651061	7	3,462
Hormone replacement therapy (HRT) for transgender and transsexual people changes the balance of sex hormones in their bodies. Some intersex people also receive HRT, either starting in childhood to confirm the sex to which they were assigned, or later, if this assignment has proven to be incorrect. The requirements for hormone replacement therapy vary immensely, often at least a certain time of psychological counseling is required. Under WPATH guidelines the Mental Health Provider requires individuals to satisfy two sets of criteria - eligibility and readiness - to undertake any stage of transition including hormone replacement therapy. Eligibility involves the patient meeting requirements from a major diagnostic tool, such as the ICD-10, DSM-IV-R or the DSM-V. ICD-10 requirements are for either Transsexualism or Gender identity disorder of childhood. The ICD-10 criteria for Transsexualism include the individual having a transsexual identity of over 2 years, a strong and persistent desire to live as a member of the opposite sex, usually accompanied by the desire to make their body as congruent as possible with the preferred sex through surgery and hormone treatments. These individuals cannot be diagnosed with Transsexualism if it is believed to be a result of another mental disorder, or a genetic, intersex or chromosomal abnormality. The ICD-10 criteria for Gender identity disorder of childhood in males include the individual being pre-pubescent and having intense and persistent distress about being a boy. The distress must be present for at least six months. The child must either: Have a preoccupation with stereotypic female activities, as shown by crossdressing, simulating female attire, or an intense desire to join in the games and pastimes of girls, rejecting male games and pastimes. Have persistent denial relating to their male anatomy. This can be shown through believing they will grow up to be a woman, that their penis or testes is disgusting or will disappear, or that it would be better not to have a penis. The DSM-IV-R criteria for Gender Identity Disorder includes four main criteria. The DSM-IV-R also requests that the individual's sexuality is noted. Strong and persistent cross-gender identity. In children this may be demonstrated by them meeting four or more of the following criteria: An insistence that one is or desires to be the other sex. Boys must display a preference crossdressing or simulating female attire, and girls must persistently wear only stereotypical male clothing. Persistent fantasies of being the other sex, or strong and persistent preference for cross-sex roles in make-believe play. Intense desire to participate in stereotypical games of the other sex. Strong preference for playmates of the other sex. Adolescents and Adults must display a persistent desire to be the other sex, frequent passing as the other sex, desire to live or be treated as the other sex, or the conviction that they have the typical feelings and reactions of the other sex. Persistent discomfort with their sex or a sense of inappropriateness in the gender role of that sex. In boys this may manifest as an assertion that their penis or testes are disgusting or will disappear, or asserting that it is better not to have a penis. The disturbance must not be concurrent with a physical intersex condition. The disturbance causes clinically significant distress or impairment in social, occupations or important areas of functioning. The DSM-V moves from Gender Identity Disorder to Gender Dysphoria to avoid the implication that gender nonconformity is in itself a mental disorder, but a similar entry remains in the DSM-V so that individuals may still seek treatment. The DSM-V, unlike the DSM-IV and ICD-10, separates Gender Dysphoria from sexual paraphilias, and diagnoses on the basis of a strong desire that one has feelings and convictions typical of the other sex, or that one strongly desires to be treated as the other sex or be rid of one's sex characteristics. The readability of patients to transition is also relevant to undertake hormone replacement therapy, which includes the patient's likelihood to take hormones in a responsible manner, have made progress in mastering other identified problems that leads to improving or continuing stable mental health, and have had further consolidation of gender identity during psychotherapy or Real Life Experience of their desired gender role. Some organizations still require a period of time living as the desired gender role, based on standards such as the Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People (WPATH). This period is sometimes called the Real Life Experience (RLE). Endocrine Society in 2009 specified that individuals should either have a documented 3 months Real Life Experience or a period of psychotherapy of length specified by the mental health provider, usually a minimum of 3 months. Some people, especially individuals from the transgender community, say that RLE is psychologically harmful and is a form of "gatekeeping" — effectively barring people from transitioning for as long as possible, if not permanently.[who?] Some individuals choose to self-administer their medication ("do-it-yourself"), often because available doctors have too little experience in this matter, or no doctor is available in the first place. Sometimes, trans persons choose to self-administer because their doctor will not prescribe hormones without a letter from the patient's therapist stating that the patient meets the diagnostic criteria for GID and is making an informed decision to transition. Many therapists require at least three months of continuous psychotherapy and/or a real life test in order to write such a letter as is suggested in the HBIGDA Standards of Care. In these circumstances, the individual may self-administer until they can get these authorizations, feeling that they shouldn't have to wait for a medical professional to be convinced of their situation. In addition, as many individuals must pay for evaluation and care out-of-pocket, expense can also be prohibitive to pursuing such therapy. Absolute: history of estrogen-sensitive cancer (for example breast cancer), history of thromboembolic disease (unless provided with concurrent anti-coagulation therapy), or history of macroprolactinoma. In such cases the patient should be concurrently followed by an oncologist, hematologist or cardiologist, or neurologist, respectively. The dosages used are often higher than replacement doses for natal women, although the official guideline for endocrinologists recommends "maintain[ing] sex hormone levels within the normal range for the person’s desired gender". Usually the dosage is reduced after an orchiectomy (the removal of the testes) or sex reassignment surgery. However, the practice of lowering estrogen doses after such operations has been carried over from the days when very high doses of estrogen were required to decrease testosterone since antiandrogens were not used. In fact, high doses (though using a less potent estrogen, estradiol, that is endogenous to the human body rather than the risky ethinyl estradiol and conjugated estrogens used in the past) are recommended during the first ten or so years of HRT to fully develop, with or without having had an orchiectomy or sex reassignment. After usually ten years or so the dosages can be reduced. Progestogens, in conjunction with prolactin, are involved in the maturation of the lobules, acini, and areola during pregnancy, which are mammary structures that estrogen has little to no effect on. However, there is at present no clinical evidence that either progesterone or progestins enhance breast size, shape, or appearance in either trans women or cisgender women, and one study found no benefit to breast hemicircumference over estrogen alone in a small sample of trans women given both an estrogen and an oral progestogen (usually 10 mg/day medroxyprogesterone acetate). However, the authors of the paper state that the sample size was too small to make any definitive conclusions, and that further studies should be carried out to confirm whether progestogens do significantly affect breast size and/or shape in trans women or not. As of 2012, no additional study has looked at the issue again. Progestogens are involved in fat distribution, increase female libidinal feelings, increase appetite, slight increase in skin oil, increases blood flow to the skin, increases the ability to sweat and lose extra heat, increase in body temperature enabling one to better tolerate the cold, healthier nails, produce a sense of calm and promote sleep, and increase energy. However, progestogens may increase skin oil and libido too much for some and there may be acne breakouts due to the increase in skin oil. In addition, these effects may actually be the result of androgenic action, which may be undesirable for most trans women. Progesterone in particular is essential for bone health and seems to have a role in skin elasticity, and nerve tissue. Other effects that have been seen with progesterone in particular (not the synthetics) include reducing spasms and relaxing smooth muscle tone, gallbladder activity is reduced, bronchi are widened (helps respiration), an anti-inflammatory agent and reduces the immune response, normalizing blood clotting and vascular tone, zinc and copper levels, cell oxygen levels, and use of fat stores for energy. Progesterone also assists in thyroid function and bone building by osteoblasts. Progestins (synthetic progestogens) are associated with an increased risk in breast cancer, which is not seen with progesterone (a bioidentical or natural progestogen). Spironolactone is the most frequently used antiandrogen in the United States because it is relatively safe and inexpensive. Cyproterone acetate is more commonly used outside of the US. Spironolactone is a 'potassium-sparing diuretic' that is also used to treat low-renin hypertension, edema, hyperaldosteronism, and low potassium levels caused by other diuretics. It can cause high potassium levels, hyperkalemia, and is therefore contra-indicated in people with renal failure or who otherwise have elevated potassium levels. Spironolactone prevents the formation of testosterone in the testis (though not in the adrenals) by inhibiting enzymes involved in its production and is an androgen receptor antagonist (prevents androgens from binding to androgen receptors). Cyproterone acetate is derived from 17α hydroxyprogesterone and suppresses gonadotropin levels (which in turn reduces testosterone levels), blocks androgens from binding to androgen receptors, and is a weak progestin. It has been used to treat prostate cancer. If used long-term in dosages of 150 milligrams or higher it can possibly lead to liver damage or failure. Other antiandrogens include bicalutamide, flutamide, and nilutamide. Unlike the two medications above, these do not lower testosterone levels but rather prevent testosterone and dihydrotestosterone from binding to androgen receptors. Because these have a weak action at the brain they do not lower libido or decrease erections. Two other antiandrogens that are rarely prescribed are ketoconazole and cimetidine. Ketoconazole has been used in those with prostatic cancer and hirsutism. Cimetidine has also been used in hirsutism. Ketoconazole has the potential of liver toxicity over long-term use and cimetidine is a relatively weak antiandrogen. Certain antiandrogens do not lower testosterone levels or prevent its action upon tissues but rather its metabolite, dihydrotestosterone (DHT), from forming. These medications can be used when the patient has male-pattern hair loss (androgenetic alopecia) and/or an enlarged prostate (benign prostatic hyperplasia). DHT contributes to the manifestation and exacerbation of both. Two medications are currently available to prevent the creation of DHT, finasteride and dutasteride. DHT levels can be lowered up to approximately 60-75% with the former depending upon dosage and up to 93-94% with the latter. In both sexes, the hypothalamus releases GnRH (gonadotropin-releasing hormone) to stimulate the pituitary to produce LH (luteinizing hormone) and FSH (follicle-stimulating hormone) which in turn cause the gonads to produce sex steroids. In adolescents of either sex with relevant indicators, GnRH analogues, such as goserelin acetate can be used to suspend the advance of sex steroid-induced, inappropriate pubert changes for a period without inducing any changes towards the sex with which the patient currently identifies. GnRH agonists work by initially over stimulating the pituitary then rapidly desensitizing it to the effects of GnRH. After an initial surge, over a period of weeks, gonadal androgen production is greatly reduced. On the other hand, GnRH antagonists act by blocking the action of GnRH in the pituitary. There is considerable controversy over the earliest age, and for how long it is clinically, morally and legally safe to do this. The current, sixth edition of the World Professional Association for Transgender HealthStandards of Care permit from Tanner stage 2, but do not allow the addition of hormones until 16, which could be five or more years. The sex steroids do have important other functions. Also, some skeletal changes (such as increased height), which may be considered masculine, are not hindered by GnRH analogues. GnRH analogues are often prescribed to prevent the reactivation of testicular function where surgeons require the cessation of estrogens prior to surgery. The high cost of GnRH analogues is often a significant factor. HRT does not usually cause facial hair growth to be impeded or the voice to change. Partially reversible changes Breast development (may need reconstructive surgery to reverse the effect) Infertility, eventually leading to chemically induced aspermatogenesis. The reversibility of this effect depends on the length of time and effects of androgen suppressing substances. Androgen suppressing drugs are not a substitute for other birth control methods. The psychological changes are harder to define, because HRT is usually the first physical action that takes place when transitioning and the act itself of beginning HRT has a significant psychological effect, which is difficult to distinguish from hormonally induced changes. What HRT cannot change HRT cannot reverse bone changes that have already been established by puberty. Consequently, total height, the length of the arms, legs, hands, and feet, and the width/size of the shoulders and rib cage are all not affected by HRT. However, details of bone shape change throughout life, with bones becoming heavier and more deeply sculptured under the influence of androgens, and HRT will prevent such changes from developing any further. The width of the hips are not affected in individuals in whom epiphyseal closure (fusion and closure of the ends of bones, which prevents any further lengthening) has taken place, an event which occurs in most people between 18 and 25 years of age. In addition, already established changes to the shape of the hips cannot be reversed by HRT whether epiphyseal closure has taken place yet or not. During puberty, the voice deepens in pitch and becomes more resonant, effects which are permanent and are not affected by HRT. Voice therapy and optionally surgery may be used instead to achieve a more female sounding voice. Facial hair develops during puberty, and this is a change that is only slightly affected by HRT. Facial hair may be permanently removed with electrolysis or laser hair removal instead. The most significant cardiovascular risk for transgender women is the pro-thrombotic effect of estrogens (Increased blood clotting.) This manifests most significantly as an increased risk for thromboembolic disease: deep venous thrombosis (DVT) and pulmonary embolism (PE) which occurs when DVTs break off and migrate through the venous system to the lungs. It is important for any person on female hormones to immediately seek medical care if she develops pain or swelling of one leg (especially calf) as this is the predominant symptom of a DVT, or if she develops symptoms of PE: chest pain, shortness of breath, fainting, or palpitations (even without leg pain or swelling). In practice this becomes very important to transgender women undergoing surgery. Ethinyl and conjugated oral estrogens should be withheld for a week before and until two weeks after surgery. DVTs occur more frequently in the first year of treatment with estrogens. However this may represent a 'screening by treatment' of patients who may have genetic predispositions to thromboembolic disease, with those who are more likely to develop DVTs doing so early on in therapy. However, if patients have a family history of thromboembolic disease, screening for known disease may be appropriate. DVT risk is higher with oral estrogen (particularly ethinyl estradiol and conjugated estrogens) rather than injectable, transdermal, implantable, and nasal estrogens. DVT risk also increases with age and with smoking, so many clinicians advise using the safer estrogen formulations in patients who smoke or are older than age 40. If screening is undertaken for known pro-thrombotic mutations such as Factor V-Leiden, antithrombin III, and protein C or S deficiency, it should be done so to increase the safety of hormonal therapy and not as a screen for who may undertake hormonal therapy. Given that the risk of warfarin treatment in a relatively young, well-informed, and otherwise healthy population is quite low and that the risk of adverse physical and psychological outcome for untreated transgender patients is high, a prothrombotic mutation is not an absolute contraindication for hormonal therapy. (See: Levy, et al. "Endocrine Intervention for Transsexuals" Clin Endo 2003. 59:409-418.) The antiandrogen bicalutamide is associated with an increased risk of heart failure when used as monotherapy (without any other drugs). A study of prostate cancer patients also showed an increased number of deaths unrelated to cancer among patients taking 150 mg/day bicalutamide. This prompted Health Canada to withdraw its approval for 150 mg bicalutamide as monotherapy. The increased death rate has not been observed where bicalutamide was combined with a method of reducing androgen production. The exact reasons for the heart failure and deaths have not been completely determined, however a likely cause is acute adrenal insufficiency and hypotension due to the action of DHT during episodes of bicalutamide withdrawal. Because bicalutamide is extremely lipophilic, it is difficult to avoid periods of low serum concentration due to the uptake of bicalutamide into fat cells. Current facial hair is only slightly affected (some reduction in density, coverage, and slower growth) by antiandrogens. Those who are less than a decade past puberty and/or whose race generally lacks a significant amount of facial hair will have better results with antiandrogens. Those taking antiandrogens will have better results with electrolysis/laser hair removal than those who are not. If one is still in their teens or early twenties, there will be prevention of new facial hairs from developing if testosterone levels are within the female range. Body hair (chest, periareolar, shoulders, back, abdomen, buttocks, thighs, tops of hands, tops of feet) will, over time, turn from terminal ("normal") hairs to vellus hairs (very tiny, blonde "baby" hairs). Hair on the arms, perianal, and perineal will reduce but may not turn to vellus hair on the latter two regions (some natal females also have some hair in these areas). Underarm hair will slightly change in texture and length, pubic hair becomes more typically female in pattern. Lower leg hair becomes less dense in concentration. All depend upon genetics. Head hair may slightly change in texture, curl, and color (new hairs that is, not hair that has already formed and reached the surface prior to HRT), this is especially likely with hair growth from previously bald areas. Eyebrow hair becomes less "bushy" or scattered. Transgender women report a sometimes significant reduction in libido, all depending on the dosage of antiandrogens. A small number of post-operative transsexual women may take small amounts of testosterone to boost the libido. Many pre-operative transsexual women simply wait until after sex-reassignment surgery to begin an active sex life (due to how they feel towards their genitals and/or an aversion to other sex acts) and for newly post-operative women how satisfied they are with the results. Raising estrogen dosage or adding a progestogen has also raised the libido of some trans women. Spontaneous and morning erections decrease in frequency significantly, however some who have had an orchiectomy still experience morning erections. Voluntary erections may or may not be possible depending on the amount of hormones and/or antiandrogens being taken; it varies a lot depending on individual biochemistry, dosing, and anatomy. Testi volume is reduced by about 25% with typical dosages and as much as 50% in higher dosages, especially after a year of HRT. This is in response to the decrease in Leydig cells, Sertoli cells, and interstitial tissue, which produce both sperm and testosterone. When testosterone is dramatically reduced spermatogenesis is halted almost completely, when the cells that are involved in these processes go unused they atrophy (shrink). Childbearing, as experienced by cisgender women, is impossible with current technology. Pre-operative sperm banking can be done, however, allowing artificial insemination to be used to produce genetic offspring with someone else at a later date. Medical advances in the near future may one day make this possible by using a donor uterus long enough to carry a child to term as anti-rejection drugs do not seem to affect the fetus. The DNA in a donated ovum can be removed and replaced with the DNA of the receiver. Further in the future stem cell biotechnology may also make this possible, with no need for anti-rejection drugs. Both estrogens and androgens are necessary in both biological males and females for healthy bone. (Young healthy women produce about 10 mg of testosterone monthly. Higher bone mineral density in males is associated with higher serum estrogen.) Bone is not static. It is constantly being reabsorbed and created. Osteoporosis results when bone formation occurs at a rate less than bone reabsorption. Estrogen is the predominant sex hormone that slows bone loss (even in men.) Both estrogen and testosterone help stimulate bone formation (T, especially at puberty.) The hips will rotate slightly forward due to changes in the tendons so hip discomfort is not uncommon. Any drug can cause adverse reactions with other medications so it is wise to check with a doctor or pharmacist when starting any new medication. Of the estrogen formulations commonly used, ethinyl estradiol (commonly found in birth control pills) has the greatest number of adverse reactions. The uppermost layer of skin, the stratum corneum, becomes thinner and therefore more translucent and pinkish (spider veins may appear or be more noticeable), less collagen, more susceptible to tearing and irritation from scratching or shaving, increased tactile sensation, and slightly lighter in color due to a slight decrease in melanin (pigment). Sebaceous gland activity (which is triggered by androgens) lessens which lowers the amount of sebum (oil) production on the skin and scalp, consequently the skin becomes less prone to the formation of acne due to the less quantity of oil that is produced. Dry skin becomes a problem and lotions and oils may be necessary. The skin's pores become smaller due to the low quantities of sebum produced Body odor (skin, sweat, and urine) will become less "metallic," "sharp," or "acrid" and more "sweet" and "musky." Many apocrine glands (type of sweat glands) become inactive and body odor decreases. Sebum also contributes to body odor, the production of which is reduced by antiandrogens (as described above). More subcutaneous fat tissue accumulates. This gives a more puffy/softer appearance. Consequently dimpling, or cellulite, will be more apparent on the thighs and buttocks due to this along with the thinness of the skin. Susceptibility to sunburn increases possibly due to the thinner skin and/or less skin pigment. Because of the increase in adipose tissue in the hips, thighs, and rear, stretch marks (striae distensae) may appear on the skin in these areas. Due to decreased androgens, the meibomian glands (aka., tarsal, palpebral, or tarsoconjunctival glands. A type of sebaceous gland on the upper and lower eyelids that open at the edges of the lids) produce less oil (oil that makes up the lipid layer of tear film which prevents the evaporation of the watery layer beneath) and a tendency for dry eyes may be a problem. Sensitivity to male body odor(s) (including male pheromones) may be positively correlated with elevated estrogen levels. Overall, olfactory senses may increase. Mammary gland development Breast, nipple, and areolar development takes 4–6 years to complete depending upon genetics, and sometimes as long as 10 years. It is normal for there to be a "stall" in breast growth during feminization, or for the size of one breast to be a little bigger than the other. Transwomen who undergo HRT often experience breast development which is below the comparable cis female norm (many seek breast augmentation); it is rare for a HRT patient to opt for breast reduction. The size of the rib cage and shoulder width also play a role in the perceivable "size" of the breasts; both characteristics are usually smaller in cis females, i.e., if a cis female and a trans female were to have the same cup size, the transwoman's breasts would most likely appear smaller. Thus when a trans woman opts to have breast augmentation, the implants used are, on the average, larger than those commonly used by cis females. The nipples often become more sensitive to stimulation. Many women in clinical trials used stem cells from fat to regrow breasts from total mastectomies.This would replace the need for artificial implantation. Adipose tissue distribution Fat distribution in the body slowly changes over months and years. The body will now tend to accumulate new adipose tissue (fat) in a typically female pattern. This includes the hips, thighs, rear, pubis, upper arms, and breasts. The body will now tend to use/burn the old adipose tissue in the waist making the waist appear smaller as well as on the shoulders and back. Subcutaneous adipose tissue increases in the face (cheeks and lips) making the face appear puffier, appears to "round out" the face, and the face appears less "drawn" or "hollow" with slightly less emphasis on the jaw due to the lower portion of the cheeks having filled in. Estrogens may predispose to gallbladder disease - especially in older and obese people. Estrogens (especially oral forms) may cause elevations in transaminases (liver function tests) indicating liver toxicity. LFTs should therefore be periodically monitored in transgender women. Mood changes can occur, such as the development of depression. However, many trans women report significant mood-lifting effects from HRT as well. In addition, the risk of depressive side effects is more particularly common in those who take progestins. Medroxyprogesterone acetate, in particular, has been shown to cause depression in certain individuals, perhaps due to its possible effect on dopamine levels; though, this effect may be largely reliant on its strong inhibitory effects on sex hormone production. Migraines can be made worse or unmasked by estrogen therapy. Estrogens can induce the development of prolactinomas, which is why prolactin levels should periodically be monitored in transgender women. Milk discharge from the nipples can be a sign of elevated prolactin levels. If a prolactinoma becomes large enough, it can cause visual changes (especially decreased peripheral vision), headaches, mood changes, depression, dizziness, nausea, vomiting, and symptoms of pituitary failure like hypothyroidism. Some people have noticed a feeling of calmness/self-contentment after starting HRT. Recent studies have indicated that cross-hormone therapy in trans women may result in a reduction in brain volume towards female proportions. Estrogen therapy causes decreased insulin sensitivity which places transgender women at increased risk of developing type II diabetes. One's metabolism slows down and one tends to gain weight, lose energy, need more sleep, and become cold more easily. Due to androgen deprivation a loss of muscle tone, a slower metabolism, and physical weakness becomes more evident. Building muscle will take more work than before. The addition of a progestogen may increase energy although an increase in appetite may be seen as well. During HRT, especially in the early stages of treatment, blood work should be consistently done to assess hormone levels and liver function. It is suggested by Endocrine Society that individuals have blood tests every 3 months in the first year of Hormone Replacement Therapy for Estradiol and Testosterone and monitor Spironolactone, if used, every 2–3 months in the first year. 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Scarabin PY, Oger E, Plu-Bureau G (August 2003). "Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk". Lancet362 (9382): 428–32. doi:10.1016/S0140-6736(03)14066-4. PMID12927428. Straczek C, Oger E, Yon de Jonage-Canonico MB, et al. (November 2005). "Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration". Circulation112 (22): 3495–500. doi:10.1161/CIRCULATIONAHA.105.565556. PMID16301339. Ockrim J, Lalani el-N, Abel P (October 2006). "Therapy Insight: parenteral estrogen treatment for prostate cancer--a new dawn for an old therapy". Nature Clinical Practice Oncology3 (10): 552–63. doi:10.1038/ncponc0602. PMID17019433. Basurto L, Saucedo R, Zárate A, et al. (2006). "Effect of pulsed estrogen therapy on hemostatic markers in comparison with oral estrogen regimen in postmenopausal women". Gynecologic and Obstetric Investigation61 (2): 61–4. doi:10.1159/000088603. PMID16192735. Hemelaar M, Rosing J, Kenemans P, Thomassen MC, Braat DD, van der Mooren MJ (July 2006). "Less effect of intranasal than oral hormone therapy on factors associated with venous thrombosis risk in healthy postmenopausal women". Arteriosclerosis, Thrombosis, and Vascular Biology26 (7): 1660–6. doi:10.1161/01.ATV.0000224325.96659.53. PMID16645152. Hedlund PO, Damber JE, Hagerman I, et al. (2008). "Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer: part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5". Scandinavian Journal of Urology and Nephrology42 (3): 220–9. doi:10.1080/00365590801943274. PMID18432528. ^Iversen P, Johansson JE, Lodding P, et al. (November 2004). "Bicalutamide (150 mg) versus placebo as immediate therapy alone or as adjuvant to therapy with curative intent for early nonmetastatic prostate cancer: 5.3-year median followup from the Scandinavian Prostate Cancer Group Study Number 6". The Journal of Urology172 (5 Pt 1): 1871–6. doi:10.1097/01.ju.0000139719.99825.54. PMID15540741. ^Rossi R, Zatelli MC, Valentini A, et al. (December 1998). "Evidence for androgen receptor gene expression and growth inhibitory effect of dihydrotestosterone on human adrenocortical cells". The Journal of Endocrinology159 (3): 373–80. doi:10.1677/joe.0.1590373. PMID9834454. ^ abcGiltay EJ, Gooren LJ (August 2000). "Effects of sex steroid deprivation/administration on hair growth and skin sebum production in transsexual males and females". Journal of Clinical Endocrinology and Metabolism85 (8): 2913–21. doi:10.1210/jc.85.8.2913. PMID10946903. ^Kirk, MD, Sheila (1999). Feminizing Hormonal Therapy For The Transgendered (1999 Edition). 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"Complete androgen insensitivity syndrome: effect on human meibomian gland secretions". Archives of Ophthalmology120 (12): 1689–1699. doi:10.1001/archopht.120.12.1689. PMID12470144. ^Cermak JM, Krenzer KL, Sullivan RM, Dana MR, Sullivan DA (August 2003). "Is complete androgen insensitivity syndrome associated with alterations in the meibomian gland and ocular surface?". Cornea22 (6): 516–21. doi:10.1097/00003226-200308000-00006. PMID12883343. ^Oprea L, Tiberghien A, Creuzot-Garcher C, Baudouin C (October 2004). "Influence des hormones sur le film lacrymal" [Hormonal regulatory influence in tear film]. Journal Français D'ophtalmologie (in French) 27 (8): 933–41. doi:10.1016/S0181-5512(04)96241-9. PMID15547478. ^Cite error: The named reference Meikle2009 was invoked but never defined (see the help page). ^Kirk, MD, Sheila (1999). Feminizing Hormonal Therapy For The Transgendered (1999 Edition). Pittsburgh, PA: Together Lifeworks. p. 52. ^Harel Z, Biro FM, Kollar LM (May 1995). 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- Fertilization Movie) Note though there can be subtle differences in the fertilization process which occurs naturally within the body or through reproductive technologies outside the body, the overall product in both cases is a diplod zygote. — “UNSW Embryology- Week 1 Fertilization”, embryology.med.unsw.edu.au - fertilization (reproduction), union of a spermatozoal nucleus, of paternal origin, with an egg nucleus, of maternal origin, to form the primary nucleus of an embryo. In all organisms the essence of fertilization is, in fact, the fusion of the. — “fertilization (reproduction) -- Britannica Online Encyclopedia”, - Fertilization Fertilization. Before she actually starts growing, you'll set the stage. Last week an increase in the amount of estrogen and progesterone coursing through your bloodstream prompted your uterus to form a lush, blood-rich lining of. — “Fertilization \| BabyCenter”, - Its the process of fertilization from where it begins. Before ovulation, mucus is These two nuclei then move to form a set of chromosomes, this them is the fertilized egg or zygote. — “human fertilization”, - In Vitro Fertilization is a process during which egg cells, which have been harvested In Vitro Fertilization is a process during which egg cells, which. — “In Vitro Fertilization”, - fertilization n. The act or process of initiating biological reproduction by insemination or pollination. — “fertilization: Definition from ”, - For fertilization in humans See: Human fertilization If fertilization takes place, the sperm usually meet the ovum in the fallopian tube, requiring the sperm. — “Fertilization - Psychology Wiki”, - After fertilization, a period of 14 days that follows is referred to as the pre-embryonic period. The process of in vitro fertilization (IVF) is widely considered to be a marvel of modern reproductive science. — “Fertilization - Topic - Associated Content from Yahoo!”, - Definition of fertilization in the Medical Dictionary. fertilization explanation. Information about fertilization in Free online English dictionary. What is fertilization? Meaning of fertilization medical term. What does fertilization mean?. — “fertilization - definition of fertilization in the Medical”, medical- - If fertilization does not take place, this ovum gets released in the mentrual phase. When is fertilization and pregnancy most likely to occur? Fertilization of an egg can. — “Fertilization”, - Get information, facts, and pictures about fertilization at . Make research projects and school reports about fertilization easy with credible articles from our FREE, online encyclopedia and dictionary. — “fertilization Facts, information, pictures \| ”, - In *ual reproduction, fertilization involves the donation of genes from two parents which results in the production of offspring with a mix of inherited genes. — “ual Reproduction: Fertilization”, - Scientific article describing fertilization, the union of an ovum and sperm usually occurring in the development of an embryo. — “Fertilisation (Conception) - Wikipedia”, - Definition and other additional information on Fertilization from Biology- dictionary. — “Fertilization - definition from Biology-”, biology- - Fertilization is more a chain of events than a single, isolated phenomenon. Fertilization by more than one sperm - polyspermy - almost inevitably leads to early embryonic death. — “Fertilization”, vivo.colostate.edu - Normally, an egg and sperm are fertilized inside a womans body. If the doctor thinks the chance of fertilization is low, the laboratory staff may directly inject the sperm into the egg. — “In vitro fertilization (IVF)”, - Fertilization. Learn about Fertilization on . Get information and videos on Fertilization including articles on wiki, vitro, miraculously and more!. — “Fertilization \| Answerbag”, - While the cost of in vitro fertilization is high, it's the last hope of conceiving a child for many couples. The average cost for one cycle of in vitro fertilization is around $12,400. Typically, this includes lab screenings for both parents, your ultrasound. — “Cost of In Vitro Fertilization - LoveToKnow Pregnancy”, - The process of In Vitro fertilization has been very popular despite it being a debatable issue for many. — “Fertilization - Pregnancy Fertilization - Pregnancy”, pregnancy- - Fertilization definition, an act, process, or instance of fertilizing. fertilization (fûr'tl-ĭ-zā'shən) Pronunciation Key. The process by which two gametes (reproductive cells having a single, haploid set of chromosomes) fuse to become a zygote, which develops into a new organism. — “Fertilization \| Define Fertilization at ”, - The egg can be fertilized for about 24 hours after ovulation. The fertilized egg (called a zygote) continues to divide as it passes slowly through the fallopian tube to the uterus where its next job is to attach. — “Pregnancy and conception”, - Definition of fertilization in the Online Dictionary. Meaning of fertilization. Pronunciation of fertilization. Translations of fertilization. fertilization synonyms, fertilization antonyms. Information about fertilization in the free online. — “fertilization - definition of fertilization by the Free”, related images for fertilization - Monosomy Fertilization CTI view large image Structural - Cement Fertilization GIF - fertilization big png - Our technician applying a granular fertilizer - Is an embryo or fetus a human When does it become a human at fertilization - A intermediate scale of disturbances are maintaining maximum biodiversity - FERTILIZATION jpg - Our fertilization crews come prepared to handle any kind of weed - Strategic Project Forest Fertilization 002 jpg - 我々と米国ベイラー医科大学の共同研究において排卵過程の卵丘細胞を材料としたマイクロアレイ解析により初期免疫に関わる因子が排卵 - potatoes and cord jpg 22 May 2009 08 57 58k Crick and Watson jpg 22 May 2009 08 16 46k fertilization diagra > 22 May 2009 08 06 52k from person to gene jpg 22 May 2009 07 57 57k - fertilization services jpg - DRGNTOY GIF 14 Feb 2009 23 27 252K Image gif ELYSIANO GIF 14 Feb 2009 23 27 113K Image gif Fertilization gif 14 Feb 2009 23 27 202K Image gif - fertilizationf jpg - menstrual cycle This animation from the CD Audio Important describes the late events in the menstrual cycle Zygote Formation If sperm are present in the oviduct at the time of ovulation fertilization takes place in the oviduct Zygotes form as a result of fertilization In fertilization the - fertilization 5 jpg - binge feed your grass Fertilizing over a period of time keeps your grass consistent As with most things overdoing it can be as harmful as doing without - the gamonts of Monocystis lumbrici have released their isogametes which are actively fusing in this view 400x - Экстракорпоральное оплодотворение ЭКО - Back to Overview - Our technician applying a granular fertilizer - Normal Fertilization CTI view large image - the soil for absorption by the root system Plant leaves are very effective at absorbing nutrients and making them available for plant growth Using Foliar Fertilizers in the Organic Garden While it s not a substitute for building a healthy fertile garden soil foliar fertilization is a great supplement for providing an extra boost to your plants in the midst of the growing - Crazy 015 - Fertilization Site - Posted by Kate Stravinskas at 11 01 00 AM \| 0 Comment s Do you want a healthy and beautiful green lawn this fall With Greenview s Zero Phosphate Fall Fertilizer you ll get the lawn you always wanted while being eco friendly Phosphorous - cell to make wouldn t you say Here s a diagrammatic look at the cellular events that take place in the ovule as an egg cell is differentiated The journey of the pollen tube is shown here And here s another drawing that might help Compare these with the beautiful photo in the book of a germinating pollen grain Everything fitting together OK A look at how one - Fertilization 1 - GCMGA2369 101 Lawn Fertilization GIF - or featured on its web site To Print Program Right click anywhere within the outline of the program and select Print or Print Picture from the drop down or pop up window that appears SEE ALSO Grow The Perfect Lawn - Trisomy Fertilization CTI view large image - Raspberry Fertilization To use any of the clipart images above including the thumbnail image in the top left corner just click and drag the picture to your desktop You may also control click Mac or right click - Information from the Virginia Cooperative Extension seminar can be viewed and downloaded by clicking on the image below Forest Lakes Neighborhood Watch - A property that subscribes to our 6 Step Fertilization Program - 1 55 N Fertilization Considerations for Cotton Nitrogen fertilization should be considered in irrigated fields making good progress Figure 1 link to figure shows a typical N uptake curve for cotton and corresponding crop development stages Suggestions for applications of approximate percentages of total N are also shown A one - Fertilization 2006 acrylic on canvas 30 x 40 SOLD - Strategic Project Forest Fertilization 022 jpg related videos for fertilization - Invitro Fertilization - A couple's story Linda and Nils had been trying for years to have a baby. They finally tried Invitro Fertilization, or IVF, and the results were doubly as gratifying! Robert Edwards won the 2010 Nobel Prize in medicine co-founding in-vitro fertilization technique. - Experts Say In Vitro Fertilization Could Lead To Eugenics Benedict XVI recalled that while scientific advances in genetics have helped improve the diagnosis of diseases, they have also presented new challenges. Benedict XVI "It is necessary to reiterate that any discrimination carried out by any power against persons, populations or ethnic groups on the basis of real or presumed genetics factors is an attack against all humanity. He spoke to scientists, theologians and philosophers participating in an international congress on genetics in Rome organized by the Pontifical Academy for Life. For three days, experts from around the world studied "The New Frontiers of Genetics and the Risks of Eugenics." The discussion focused on studying the practices of genetics that lead to considering that some unhealthy embryos are less useful than healthy ones and must be eliminated. Msgr. Rino Fisichella The word eugenics seemed to be a word that pertained to the past but in fact its still valid because an eugenic mentality is growing and perhaps the greatest dangers is that although the term is not used, the mentality that not all people have the same dignity is being assumed. The participants were especially alarmed by the selection of embryos during in vitro fertilization because it eliminates those who have genetic diseases like cystic fibrosis or Down syndrome. Msgr. Ignacio Carrasco The case of children with Down syndrome. Today those children practically are no longer born because they eliminate the problem of Down syndrome by ... - About In Vitro Fertilization In vitro fertilization requires stimulating the female with hormones, mixing the eggs and sperm outside the body and implanting them back into the female to hopefully conceive. Understand this method of reproduction suitable for infertile couples with helpful information from a practicing ob-gyn in this free video on getting pregnant. Expert: Lisa Gibbons Bio: Lisa Gibbons is an OB/GYN at Cascadia Women's Clinic in Vancouver, Washington. - Plant Reproduction: Plant Fertilization () *CLICK HERE for RELATED CONTENT Plant Breeding - FREE NEWSLETTERS - - IVF In Vitro Fertilization Birth - The Creation of Life(: Logan Thomas was created 11-17-05 by way of IVF (Invertrofertilzation or a test tube baby) He is a miricle for us all that's for sure! To see him being a four cell embryo too clapping hands now is some thing words can't explain! My song I added to it was written a long time ago and was not intended for this video, but it seems to almost fit? I hope you enjoy and stay subscribed to more of my videos to come. Peace outy! TAMMpON - Sea Urchin Fertilization Fertilization of eggs of the sea urchin species Strongylocentrotus purpuratus and formation and elevation of the fertilization membrane. Real time. View full screen. - In Vitro Fertilization in Mexico Mexico is a popular destination for people looking for low cost in vitro fertilization abroad. IVF (also known as Assisted reproductive technology; ART; Test-tube baby procedure) usually requires a trip of two weeks. Low cost IVF destinations abroad include Mexico, Turkey, India & Jordan. IVF steps involve : Stimulation, Egg retrieval, Insemination and Fertilization, Embryo culture, Embryo transfer. In vitro fertilization costs in Mexico should also consider the cost of travel and a long stay. Fertility treatment in mexico at reputed clinics has good success rates. Cheap IVF clinics in Mexico do not always equate to poor quality. Mexico has Affordable IVF price due to lower drug costs & other medical expenses. Beach resorts of Manzanillo, Mazatlan and Puerto Vallarta are very near to the location of this Mexico ivf clinic. - News Update: In Vitro Fertilization Developer Wins Nobel Prize The Nobel Foundation has announced the first in 6 awards that recognize outstanding cultural and scientific advances. Monday's prize announcement was for Physiology or Medicine. SOT: ""...the Nobel Prize in Physiology or Medicine 2010 to Robert Edwards for the development of in vitro fertilization."" The English biologist, along with his partner Patrick Steptoe who would have shared the prize if he were still alive, spent more than 20 years working to get eggs and sperm to mature and unite outside the body. They made the discovery 30 years ago. Today, 1-2% of all births in the US are a result of the revolutionary IVF method. The treatment has seen the conception of around 4 million babies since the first test tube baby, Louise Brown, in 1978. The procedure, which was originally met with much controversy because of the moral implications of intervening in the creation of a human being, is now more widely accepted and has helped hopeful parents overcome infertility. The Nobel Foundation will award prizes everyday this week, with the final announcement next Monday. The organization will recognize outstanding individuals in physics, chemistry, literature, the economic sciences and peace. - In Vitro Fertilization? What is the relevant biblical wisdom regarding the complex ethical decisions surrounding in vitro fertilization? Is it an open handed issue or is IVF to always be avoided by Christians?Pastor Mark Driscoll answers this question as part of a live "Ask Anything" session in which audience members SMS questions to the pulpit to be answered in real time. This question was answered in the broader context of a sermon entitled "Is Birth Control a Sin?" which can be found at - In Vitro Fertilization at UAB: One Couple's Success Story In Vitro Fertilization helped Jennifer and Gregg Fleming start a family. Infertility specialists at UAB discuss the benefits of coming to UAB for infertility treatment. - Sea Urchin Fertilization This video shows the process of fertilization in a sea urchin. This video is from: Essential Cell Biology, 3rd Edition Alberts, Bray, Hopkin, Johnson, Lewis, Raff, Roberts, & Walter ISBN: 978-0-8153-4129-1 - FRIED OR FERTILIZED- Yung Humma ft Flynt Flossy and Whatchyamacallit Download on iTunes NOW!! JOIN TURQUOISE JEEP ON FACEBOOK . FOLLOW ON TWITTER Newly signed Hip Hop sensation YUNG HUMMA debuts with his new hit single and dance phenomenon "FRIED OR FERTILIZED" featuring FLYNT FLOSSY and WHATCHYAMACALLIT DIR: G.WINTERS (c)TURQUOISE JEEP RECORDS 2010 - 3D sperm fertilization project 3D models of (sperm, fallopian tubes, white blood cell hehe) used in a particle system. An overuse of 2-headed and 2-tailed sperm is used for fun. Also after reading a sidenote that some white blood cells can kill sperm setups a cool lil' animation that probably rarely happens in real life. Original music had Wagner's Ride of the Valkyries as the music but had to swap that out, and this track was pretty darn cool anyway :) - In Vitro Fertilization IVF Superior ART is an infertility treatment center with recognized expertise specializing in a method to diagnose embryos with chromosomal and single genes disorders in order to provide solutions for couples with infertility and repeated miscarriage or those who gave birth to children with inherit disease, such as beta thalassemia or genetic abnormality like Robertsonian translocation. In the old days, as there was no treatment to the problems, the couples had to take all the risk of getting pregnant and repeated miscarriage. But today, thanks to the Assisted Reproduction Technology, Superior ART is capable of helping couples to get through such problems. Why Superior ART? Thats because at Superior ART, we have available the expertise and advanced technology to diagnose genetic health of the embryos and select those without any genetic diseases to be transferred to the uterus. There was a case of a couple who experienced problems of repeated miscarriage due to genetic abnormality of Robertsonian translocation. They received IVF treatment and PGD in which genetic material from the embryos is tested to see if they carry the genetic disease. Then only embryos not affected by the disease are transferred to the mothers womb. At the end, they achieved a pregnancy and gave birth to very healthy twin girls. - How To Fertilize Bermuda Grass Lawns Learn tips on how to properly fertilize Bermuda grass lawns. From the Southwest Yard & Garden series. - In-Vitro Fertilization (IVF) 101 (Pregnancy Health Guru) It's expensive and invasive--but if you are trying to get pregnant, it often works. Here is the real deal with IVF. More Videos on Infertility: - Fertilization: A Sweet Love Story This is my video for Professor Talbot's CBNS 169 class on the fertilization process. It took me a couple of trial and error ideas to finally get it right with using only candy. CBNS 169 Winter 09 Professor Talbot TA: John Ta Section 22 I'd like to give a special thanks to few people who made this happen: My mom, who helped me with the sorting of the Skittles (which is harder than it sounds) and endured my frustration with this project. Robert Hassaballa who helped me pick out the candy to use in the project (and also helped out with "getting rid" of the candy I didn't need). And Mina Youssef for helping me out with the idea. Some of the candy I used was skittles, starburst, gushers, fruit by the foot, reeses, twizzlers, and airheads. - Human Fertilization the animation of human fertilization - Human Fertilization.FECUNDACION OR .co..Blog Name"AALOJAMIENTO INTERNACIONAL".-Fertilization occurs when spermatozoa travels up into the uterus, an a spermatozoon encounters an egg. Pregnancy occurs as a result of the fertilization of an ovum by sperm. - Health Matters: Fertility and In Vitro Fertilization (IVF) In the US today, over 6 million people are affected by infertility. What should be the most joyous time in a couple's life can often become the most difficult. This complex issue requires the latest medical technology with the equally important need for empathetic care. To help couples on this journey, Dr. Granet is joined by a nationally recognized expert, Arlene Morales, MD, Fertility Specialists Medical Group, as she talks about the latest fertility treatments and what the best options are given the situation. Series: "Health Matters" [9/2007] [Health and Medicine] [Show ID: 12319] - In Vitro Fertilization (IVF) -- Greenville and Spartanburg, S In this video, Dr. John Nichols explains the In Vitro fertilization procedure. At our Greenville and Spartanburg, SC fertility centers, IVF is one of many advanced infertility treatments. For more information, visit - Biology 1A - Lecture 32: Fertilization and embryogenesis General Biology Lecture - Fertilization & Fetal Development Video on the development of the fetus from an embryo - InVitro Fertilization IVF This video explans the basics of IVF using Family Guy's Stewie! This is an assignment for cbns 169. - Fertilizing Dahlias Fertilization - In Vitro Fertilization (IVF) - Kurena's Treatment Story Kurena's tests revealed that she had thyroid tumors in addition to polycystic ovarian syndrome (PCOS). Treating these conditions involved removing the tumors, ovarian drilling, and follicular reduction. During this process, our doctors extracted, froze, and stored ten eggs at our Atlanta, Georgia, office for use in in vitro fertilization (IVF). A few months later, Kurena was pregnant. For more information about in vitro fertilization,please visit us at Georgia Reproductive Specialists Atlanta, GA Phone 404-975-0466 Fax: 404-843-0812 2 Office Locations: 5445 Meridian Mark Road Suite 270 Atlanta, GA 30342 3400-C Old Milton Parkway Suite 475 Alpharetta, GA 30005 - Catholic Church Attacks 'In Vitro Fertilization' in Poland November 28, 2009 on Russia Today - The Roman Catholic Church has lambasted the use of in vitro fertilization (IVF), and has taken steps to have it banned altogether, while for some families it is the only way to have children in Poland. via - - Day 1 (Fertilisation check) The next day, whether "classic" IVF or ICSI has been performed, fertilization is confirmed by observing 2 pro-nuclei (one containing half the number of chromosomes from the mother, the other containing the other half from the father). - Ancient technologies of seed fertilization with John Burke John Burke, an expert on ancient technologies of seed fertilization, is the author of the book Seed of Knowledge Stone of Plenty: Undertstanding the Lost Technologies of the Megalith-Builders with Kaj Halberg - Fertilized Human Eggs are Child ...with Bacon too Fertilized Human Egg Story: College Student Study Story: How bacon is made: Thanks a ton for watch, don't forget to subscribe :) Connect With Me http http - BONSAI-EASY NEW METHOD-PART 4-REPOTTING, FERTILIZING THIS IS PART FOUR OF "ADVENTURES IN BONSAI." THIS EPISODE COVERS REPOTTING A ROOT-BOUND MING TREE, FERTILIZATION, AND TOOLS THAT I USE IN CARING FOR MY BONSAI. TO LEARN MORE ABOUT THE BASIC STARTING OF A BONSAI USING THE NEW EASY METHOD OF SPHAGNUM MOSS AS A SUBSTRATE, SEE PARTS 1 AND 2. FOR AN UPDATE ON THE TREE WORKED ON IN PARTS 1 1ND 2, SEE PART 3.(May, 2008- showing traditional bonsai at the Morikami Museum. It's just a silent look at their trees, but it is inspiring)("Morikami Bonsai Gardens May 2008").(PLEASE VIEW PART 12 ABOUT THE WARNING ON HANDLING SPHAGNUM MOSS BEFORE YOU WORK WITH SPHAGNUM MOSS). Videographer-Carol L. - In vitro Fertilization (IVF) W09 CBNS 169 Video Project by Xiaowei Ma: "In vitro Fertilization." In vitro fertilization (IVF) is one of the best known assisted reproductive technologies that will help couples experiencing infertility problems. This video briefly describes the procedures, costs, probabilities, benefits, and results involved in IVF. Enjoy! - Fertility In Vitro Fertilization (IVF) ... Gifted Journeys ... By GloZell Straight and Gay coulples can have children. Wendie Wilson from Gifted Journeys chats with good friend GloZell about when to have kids... and more! - Fertilization CBNS 169 The process of Fertilization! The music that I originally had for this video was completely different from what you hear now...there was a bit of a problem with youtube's copyright issue... a special shout out to my sister and to my friend kevin for helping with all the technical difficulties! =) enjoy! - In Vitro Fertilization IVF Infertility Treatment Georgia Reproductive Specialists ()provides the latest in assisted reproductive technologies such as in vitro fertilization (IVF), ICSI, preimplantation genetic diagnosis (PGD)blastocyst transfer, egg donation, embryo cryopreservation, ovulation induction and insemination to couples with infertility problems due to endometriosis, polycystic ovary syndrome (PCOS), male factor, fallopian tube obstruction, uterine fibroids and age related issues. GRS offers convenienently located offices in Alpharetta, Northside and Decatur. For more information visit us online at , call 404-843-2229 or simply attend a free educational seminar "IVF AFTER HOURS" held monthly at our Northside office. - In Vitro Fertilization Pioneer, Robert Edwards, Awarded Nobel Prize Read the Transcript: This year's first Nobel Prize was awarded to Robert Edwards for his work developing the in-vitro fertilization method that led to the birth of the world's first "test-tube baby." - Sea urchin fertilization This is a movie of sea urchin egg fertilization (species: Lytechinus variegatus). Note that you can see the sperm fertilizing each egg, including both the head and the tail. Also note the formation of a fertilization cone around the sperm after initial contact with the egg. Sperm binding initiates a series of intracellular signaling events that result in the elevation of the fertilization envelope (clear membrane surrounding the fertilized egg). The fertilization envelope prevents the egg from being fertilized by more than one sperm (a fatal event) and protects the developing embryo during early development. It takes about 1-2 minutes for the fertilization envelope to rise completely after sperm binding. - Human embryology/** education: Fertilization and Implantation animation Implantation is a very hard subject for many students to grasp so I made this animation. Hope it helps- by Nhan Do BGM: Beyoncé Single Ladies (Put A Ring On It) from the album Single Ladies (Put A Ring On It) (C) 2008 SONY BMG MUSIC ENTERTAINMENT ^ buy her album _______________________ ... - Double Fertilization in Flowering Plants Double fertilization in flowering plants involves the fusion of two sperm cell nuclei of the male gametophyte with two cell nuclei of female gametophyte. One sperm fuses with the haploid egg cell to form the zygote; the other sperm unites with the diploid central cell to form a triploid cell that will develop to an endosperm. twitter about fertilization Blogs & Forum blogs and forums about fertilization “After tubal ligation, what are your options for conceiving again? Tubal ligation reversal can reopen the fallopian tubes. But, if your tubes were cut or burned there will not be enough tube to put back together. If it has been more than 10” — Tubal Ligation Reversal or IVF? - Our Blog, “Subscribe to the Andy Blog and receive an email notifications to alert you of a new post. Invitro Fertilization - All I know about IVF. News about IVF. Medical” — The Andy Blog: Invitro Fertilization Archives, .mx “Life Training Institute Blog. Persuasively Communicating the Pro-Life claiming the capacity to interrupt the fertilization process and not redefine the new” — Life Training Institute Blog: Lee & George on Fertilization, lti- “Henrik Falck's blog. reinventing web 3.0. Self-fertilization, or: web and the reason I figured I'd write this blog post at all: In their reception they had” — Self-fertilization, or: web 3.0, or: Mixi, or: One of those, “Following the SRI guidelines (see Fertilization Blog Entry), we hoped to replace chemical fertilizers with application of organic where the manure was piled before it was spread over the field (see picture in Fertilization Blog Entry)” — Yellowing of Fields, “Blog. fertilization. Share. Print. Email a Friend. Facebook. Mark as Favorite. Blog: rights, down syndrome, fertilization, john mccain, kristi burton,” — All Blog Posts - Blog - Eternal Perspective Ministries, “Plant It Landscape is a quality landscape designer, architect and contractor. We also provide fertilization services. This landscaping company proudly Thanks for stopping by our Sarasota Landscape and Fertilization Blog. We look forwarding to hearing from you! As a reminder, we certainly welcome” — Sarasota Landscape Company – Designer Architect Contractor, “Tubal Reversal Blog in vitro fertilization' Tubal Reversal After 40 : This blog is to share observations, experiences, and thoughts about tubal ligation reversal developed over the 30 years I have been performing” — Blog Posts Tagged In Vitro Fertilization - Part 2, tubal- “Read our IVF Procedures Blog for more information! The risks of retrieval involve ZIFT is a procedure that involves an oocyte retrieval followed by in vitro fertilization” — Pacific Fertility Center Los Angeles California,	2	29	2	0	0	1	0.465073	3	6,796
\|Part of a series on\| Transsexualism is when an individual identifies with a gender inconsistent or not culturally associated with their assigned sex, i.e. in which a person's assigned sex at birth conflicts with their psychological gender. A medical diagnosis can be made if a person experiences discomfort as a result of a desire to be a member of the opposite gender, or if a person experiences impaired functioning or distress as a result of that gender identification. Transsexualism is stigmatized in many parts of the world, but it has become more widely known in Western culture since the mid to late 20th century, concurrently with the sexual revolution and the development of sex reassignment surgery (SRS). - 1 Diagnosis - 2 Relation to gender roles - 3 Origins - 4 Relation to transgenderism - 5 Terminology - 6 Prevalence - 7 Causes - 8 Sex reassignment therapy - 9 Legal and social aspects - 10 Coming out - 11 In the media - 12 Thailand - 13 History and other cultures - 14 Customs and traditions - 15 Organizations - 16 See also - 17 References - 18 Bibliography - 19 External links Transsexualism appears in the two major diagnostic manuals used by mental health professionals worldwide, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM, currently in its fifth edition) and the International Statistical Classification of Diseases and Related Health Problems (ICD, currently in its tenth edition). The ICD-10 incorporates transsexualism, dual role transvestism, and gender identity disorder of childhood into its gender identity disorder category. It defines transsexualism as "[a] desire to live and be accepted as a member of the opposite sex, usually accompanied by a sense of discomfort with, or inappropriateness of, one's anatomic sex, and a wish to have surgery and hormonal treatment to make one's body as congruent as possible with one's preferred sex." The DSM does not distinguish between gender identity disorder and transsexualism, and defines transvestic fetishism as a separate phenomenon which may co-occur with transsexualism. The DSM diagnosis requires four components: - A desire or insistence that one is of the opposite biological sex (that is not due to a perceived advantage of being the other sex). - Evidence of persistent discomfort with, and perceived inappropriateness of the individual's biological sex. - The individual is not intersex (although a diagnosis of GID Not Otherwise Specified is available, which enables intersex people who reject their sex-assignment to access transsexual treatments). - Evidence of clinically significant distress or impairment in work or social life. \|This section needs additional citations for verification. (July 2009)\| The current diagnosis for transsexual people who present themselves for psychological treatment is "gender dysphoria" (leaving out those who have sexual identity disorders without gender concerns). The DSM changed its terminology in 1994. According to the Standards Of Care formulated by the World Professional Association for Transgender Health (WPATH), formerly the Harry Benjamin International Gender Dysphoria Association, this diagnostic label is often necessary to obtain sex reassignment therapy with health insurance coverage, and states that the designation of gender identity disorders as mental disorders is not a license for stigmatization, or for the deprivation of gender patients' civil rights. However, some people diagnosed with gender identity disorder have no desire for sex reassignment therapy, nor for genital reassignment surgery, and/or are not appropriate candidates for such treatment. While some feel that formal diagnosis helps to destigmatize transsexualism, others feel that it only adds stigma. They contend that such a diagnosis is equivalent to saying something is wrong with transsexual people. Some transsexual people consider the diagnosis to be a causal factor in instances of harm or death of transsexual people as the result of prejudice and discrimination when deprived of their civil rights. (Brown 105) Many transsexual people have asked the American Psychiatric Association to remove Gender Identity Disorder from the DSM, and the World Health Organization to remove it from ICD-10, where it has been listed for some time. Some believe that at least some mental health professionals are being insensitive by labeling transsexualism as "a disease", rather than as an inborn trait, which those who have it believe it to be. The Principles 18 of The Yogyakarta Principles, documents on international human rights law opposes such diagnosis as mental illness as medical abuse, as well as "Activist's Guide to the Yogyakarta Principles". In response to these concerns, in 2013 the American Psychiatric Association revised the DSM-4's criteria for diagnosing gender identity disorder, and retitled this condition to "gender dysphoria" in the DSM-5. Relation to gender roles \|This section does not cite any references or sources. (January 2011)\| Transsexual people may refer to themselves as trans men or trans women. Transsexual people often desire to establish a permanent gender role as a member of the gender with which they identify. Some transsexual people pursue medical interventions as part of the process of expressing their gender. These medically based, physical alterations are collectively referred to as sex reassignment therapy, and may include female-to-male or male-to-female hormone replacement therapy, or various surgeries. Surgeries may include genital surgery such as orchiectomy or sex reassignment surgery; chest surgery such as top surgery or breast augmentation; or, in the case of trans women, facial surgery such as trachea shave or facial feminization surgery. The entire process of switching from one physical sex and social gender presentation to another is often referred to as transition, and usually takes several years. Not all transsexual people undergo a physical transition. Some find reasons not to, for example, the expense of surgery, the risk of medical complications, medical conditions which make the use of hormones or surgery dangerous. Some may not identify strongly with another binary gender role. Others may find balance at a mid-point during the process, regardless of whether they are binary-identified. Many transsexual people, including binary-identified transsexual people, do not undergo genital surgery, because they are comfortable with their own genitals, or because they are concerned about nerve damage and the potential loss of sexual pleasure and orgasm. This is especially so in the case of trans men, many of whom are dissatisfied with the current state of phalloplasty, which is typically very expensive, not covered by health insurance, and which does not result in a fully erectile, sexually sensate penis. Some transsexual people live heterosexual lifestyles and gender roles, while some identify as gay, lesbian, or bisexual. Many trans people find that a shift occurs in their sexual orientation as they undergo transition. Many transsexual people choose the language of how they refer to their sexual orientation based on their gender identity, not their morphological sex, though some transsexual people still find identification with their community: many trans men, for instance, are involved with lesbian communities. Gender was originally a linguistic term. In many languages, words can be considered masculine, feminine, or neutral, completely independently from the attributes of the things to which the word applies. Different languages manifest gender in various ways, recognizing two genders (female, male), three genders (female, male, neuter), or in some cases none at all. In some (e.g. the Romance languages), variation by gender is indicated by relatively simple changes in nouns and adjectives, while others require more complex grammatical changes. In English, a transsexual person's first step in transition often includes the request to be referred to using pronouns for their target gender (she rather than he, her rather than him, and hers rather than his, or vice versa). Some English speakers[who?] who feel that they are best described as something in between or other than masculine or feminine prefer to use "they" and "them", as well as “ze” and “hir” (examples of gender-neutral pronouns in English) or other invented neutral pronouns. Norman Haire reported that in 1921, Dora-R of Germany under the care of Magnus Hirschfeld, began surgical transition from 1921, ending in 1930 with a successful genital reassignment surgery. In 1930, Hirschfeld supervised the second genital reassignment surgery to be reported in detail in a peer-reviewed journal on Lili Elbe of Denmark. The German term, “Transsexualismus,” was introduced by Hirschfeld in 1923. The neo-Latin term “psychopathia transexualis” and English “transexual” were introduced by D. O. Cauldwell in 1949, who subsequently also used the term “trans-sexual” in 1950. Cauldwell appears to be the first to use the term to refer to those who desired a change of physiological sex. (In 1969, Benjamin claimed to have been the first to use the term “transsexual” in a public lecture, which he gave in December 1953.) This term continues to be used by the public and medical profession alike. It was included for the first time in the DSM-III in 1980 and again in the DSM-III-R in 1987, where it was located under Disorders Usually First Evident in Infancy, Childhood or Adolescence. The word transsexual was used by Harry Benjamin in his seminal 1966 book, The Transsexual Phenomenon, to describe transsexual people on a scale (later called the "Benjamin scale") that recognizes three levels of intensity of transsexualism: "Transsexual (nonsurgical)", "Transsexual (moderate intensity)", and "Transsexual (high intensity)". In his book, Benjamin described "true" transsexualism as the following: "True transsexuals feel that they belong to the other sex, they want to be and function as members of the opposite sex, not only to appear as such. For them, their sex organs, the primary (testes) as well as the secondary (penis and others) are disgusting deformities that must be changed by the surgeon's knife." Benjamin suggested that moderate intensity male to female transsexual people may benefit from estrogen medication as a "substitute for or preliminary to operation." Some people have had SRS but do not meet the common definition of a transsexual (e.g., Gregory Hemingway). Other people do not desire SRS although they meet Dr. Benjamin's definition of a "true transsexual". Beyond Benjamin's work, which focused on male-to-female transsexual people, there are cases of the female to male transsexual, for whom genital surgery may not be practical. Benjamin gave certifying letters to his MTF transsexual patients that stated 'Their anatomical sex, that is to say, the body, is male. Their psychological sex, that is to say, the mind, is female'. Beyond 1967 Benjamin abandoned his early terminology and adopted that of "gender identity." Relation to transgenderism \|This section needs additional citations for verification. (August 2009)\| Transsexualism is often included within the broader category of transgenderism, which is generally used as an umbrella term for people who do not conform to typical accepted gender roles. It includes cross-dressers, transvestites, and people who identify as genderqueer. Transsexualism refers to a specific condition in the transgender realm. Although an individual who crossdresses and an individual who identifies as transsexual are both classified as transgender people, their identities differ radically. Though some people use transgenderism and transsexualism interchangeably, they are not synonymous terms. The term transsexual originated in the medical and psychological communities, and is an older term than transgender. Many prefer the term transgender and consider transsexual to be outdated and derogatory, due to its roots in describing the identity as a disease. Additionally, transsexual is considered a misnomer by some people because the underlying condition is related to gender identity and not sexuality. Others prefer to identify as transsexual, and object to being included in the transgender spectrum. Anthropologist David Valentine provides context for this objection in his 2007 book Transgender, an Ethnography of a Category. He writes that transgender is a term coined and used by activists to include many people who do not necessarily identify with the term. He observes that many current health clinics and services set up to serve gender-variant communities employ the term, but that most of the service-seekers do not identify with this term. The rejection of this political category, first coined by self-identified activist Leslie Feinberg, illustrates the difference between a self-identifier and categories imposed by observers to understand other people. However, these observations are contested by the Transgender Health Program at Fenway Health in Boston. They note that there are no universally accepted definitions, and terminology confusion is common because terms that were popular in at the turn of the 21st century may now be deemed offensive. They suggest that transgender is the more widely accepted term. They recommend that clinicians avoid the term transsexual unless they are sure that a client is comfortable with it. It is best to ask an individual which term, if any, is preferred. Historically the reason that transsexual people rejected associations with the transgender or broader LGBT community is largely that the medical community in the 1950s through the late 1980s encouraged this rejection of such a grouping in order to qualify as a 'true transsexual' who would thus be allowed to access medical and surgical care. The animosity that is present today is no longer fed by this same kind of pressure from the medical community. Though the beliefs of some modern-day transsexual people that they are not "transgender" reflect this historical division, other transsexual people state that those who do not seek SRS are very different from those who need to be of "the other sex", and that these groups have different issues and concerns and are not doing the same things. The latter view is rather contested, with opponents pointing out that merely having or not having some medical procedures hardly can have such far-reaching consequences as to put those who have them and those who have not into such distinctive categories. Notably Harry Benjamin's original definition of transsexualism does not require that they need to have had SRS. The word "transsexual" is most often used as an adjective rather than a noun – a "transsexual person" rather than simply "a transsexual". Transsexual people prefer to be referred to by the gender pronouns and terms associated with their target gender. For example, a transsexual man is a person who was assigned the female sex at birth on the basis of his genitals but, despite that assignment, identifies as a man and is transitioning or has transitioned to a male gender role. He has or will have a masculine body. Transsexual people are sometimes referred to with "assigned-to-target" sex terms such as "female-to-male" for a transsexual man or "male-to-female" for a transsexual woman. These terms may be abbreviated as "M2F", "F2M", "MTF", "FTM", "F to M", etc. Individuals who have undergone and completed sex reassignment surgery (SRS) are sometimes referred to as transsexed individuals; however, the term transsexed is not to be confused with the term transexual, which can also refer to individuals who have not yet undergone SRS, and whose anatomical sex (still) does not match their psychological sense of personal gender identity. The term "gender dysphoria" and "gender identity disorder" were not used until the 1970s, when Laub and Fisk published several works on transsexualism using these terms. "Transsexualism" was replaced in the DSM-IV by "gender identity disorder in adolescents and adults". Male-to-female transsexualism has sometimes been called "Harry Benjamin's Syndrome" after the endocrinologist who pioneered the study of dysphoria. As noted above, the present-day medical study of gender variance is much broader than Benjamin's early description. Use of this term has been criticized for delegitimizing gender-variant people with different experiences. The DSM-IV (1994) says that roughly 1 in 30,000 assigned males and 1 in 100,000 assigned females seek sex reassignment surgery in the US. The most frequently quoted estimate of prevalence is from the Amsterdam Gender Dysphoria Clinic The data, spanning more than four decades in which the clinic has treated roughly 95% of Dutch transsexual clients, gives figures of 1:10,000 among assigned males and 1:30,000 among assigned females. Though no direct studies on the prevalence of GID have been done, a variety of clinical papers published in the past 20 years provide estimates ranging from 1:7,400 to 1:42,000 in assigned males and 1:30,040 to 1:104,000 in assigned females. Olyslager and Conway presented a paper at the WPATH 20th International Symposium (2007) arguing that the data from their own and other studies actually imply much higher prevalence, with minimum lower bounds of 1:4,500 male-to-female transsexual people and 1:8,000 female-to-male transsexual people for a number of countries worldwide. They estimate the number of post-op women in the US to be 32,000 and obtain a figure of 1:2500 male-to-female transsexual people. They further compare the annual incidences of SRS and male birth in the U.S. to obtain a figure of 1:1000 MTF transsexual people and suggest a prevalence of 1:500 extrapolated from the rising rates of SRS in the U.S. and a "common sense" estimate of the number of undiagnosed transsexual people. Olyslager and Conway also argued that the U.S. population of assigned males having already undergone reassignment surgery by the top three U.S. SRS surgeons alone is enough to account for the entire transsexual population implied by the 1:10,000 prevalence number. This excludes all other U.S. SRS surgeons, surgeons in countries such as Thailand, Canada, and others, and the high proportion of transsexual people who have not yet sought treatment, suggesting that a prevalance of 1:10,000 is too low. A study in 2008 examined the number of New Zealand passport holders who changed the sex on their passport and estimated that 1:3,639 birth-assigned males and 1:22,714 birth-assigned females were transsexual. A presentation at the LGBT Health Summit in Bristol, UK, based upon figures from a number of reputable European and UK sources, shows that this population is increasing rapidly (14% per year) and that the mean age of transition is actually rising. Psychological and biological causes for transsexualism have been proposed, i.a. by professor Dick Swaab, with evidence leaning toward prenatal and genetic causes. One such proposed cause is related to the bed nucleus of a stria terminalis, or BSTc, a constituent of the basal ganglia of the brain which is affected by prenatal androgens. In one study, the BSTc of male-to-female transsexual women was similar to those of cisgender women whose psychological gender identity and assigned sex are the same. However, those of both heterosexual and homosexual men were similar to each other but different from those of women (both cis- and transsexual). Another study suggests that transsexuality may have a genetic component. There is considerable evidence that prenatal exposure to endocrine-disrupting anti-miscarriage drugs such as diethylstilbestrol (DES) may also be positively associated with transsexualism, though research in this area has yet to establish a firm causal link. Some people consider research into the "causes" of transsexualism to be based on the possibility that it is a pathology, a possibility that is rejected by many transsexual people. Others think of the condition as a form of intersexuality, and support research into possible causes, believing that it will verify the theory of a biological origin and thereby reduce social stigma by demonstrating that it is not a delusion, a political statement, or a paraphilia. Note that social stigma has a role to play in the development of and adherence to both viewpoints. See the transfeminism article's section on GID for further discussion. Harry Benjamin wrote, "Summarizing my impression, I would like to repeat here what I said in my first lecture on the subject more than 10 years ago: Our genetic and endocrine equipment constitutes either an unresponsive, sterile, or a more or less responsive, that is to say, fertile soil on which the wrong conditioning and a psychic trauma can grow and develop into such a basic conflict that subsequently a deviation like transsexualism can result." Sex reassignment therapy Sex reassignment therapy (SRT) is an umbrella term for all medical treatments related to sex reassignment of both transgender and intersexual people. Though SRT is sometimes called "gender reassignment", those who use the word "sex" to describe an individual's biology and "gender" to describe their personal identity and social role consider this usage to be misleading. The process of changing from one gender presentation to another is often called transition. Individuals make different choices regarding sex reassignment therapy, which can include hormone replacement therapy (HRT) to modify secondary sex characteristics, sex reassignment surgery to alter primary sex characteristics, facial feminization surgery and permanent hair removal for trans women. Transsexual people who transition usually change their social gender roles, legal names and legal sex designation. To obtain sex reassignment therapy, transsexual people are generally required to undergo a psychological evaluation and receive a diagnosis of gender identity disorder in accordance with the Standards of Care (SOC) as published by the World Professional Association for Transgender Health. This assessment is usually accompanied by counseling on issues of adjustment to the desired gender role, effects and risks of medical treatments, and sometimes also by psychological therapy. The SOC are intended as guidelines, not inflexible rules, and are intended to ensure that clients are properly informed and in sound psychological health, and to discourage people from transitioning based on unrealistic expectations. Psychological techniques that attempt to alter gender identity to one considered appropriate for the person's assigned sex are typically ineffective. The widely recognized Standards of Care note that sometimes the only reasonable and effective course of treatment for transsexual people is to go through sex reassignment therapy. The need for treatment is emphasized by the high rate of mental health problems, including depression, anxiety, and various addictions, as well as a higher suicide rate among untreated transsexual people than in the general population. These problems may be alleviated by a change of gender role and/or physical characteristics. Many transgender and transsexual activists, and many caregivers, note that these problems are not usually related to the gender identity issues themselves, but the social and cultural responses to gender-variant individuals. Some transsexual people reject the counseling that is recommended by the Standards of Care because they don’t consider their gender identity to be a psychological problem. Brown and Rounsley noted that "[s]ome transsexual people acquiesce to legal and medical expectations in order to gain rights granted through the medical/psychological hierarchy." Legal needs such as a change of sex on legal documents, and medical needs, such as sex reassignment surgery, are usually difficult to obtain without a doctor and/or therapist's approval. Because of this, some transsexual people feel coerced into affirming outdated concepts of gender to overcome simple legal and medical hurdles (Brown 107). After an initial psychological evaluation, men and women may begin medical treatment starting with hormone replacement therapy or hormone blockers. People who change sex are usually required to live as members of their target sex for at least one year prior to genital surgery, gaining real-life experience sometimes called the "real-life test" (RLT). Transsexual individuals may undergo some, all, or none of the medical procedures available, depending on personal feelings, health, income, and other considerations. Some people posit that transsexualism is a physical condition, not a psychological issue, and assert that sex reassignment therapy should be given on request. (Brown 103) Regrets and detransitions People who undergo sex reassignment surgery can develop regret for the procedure later in life, largely due to lack of support from family or peers, with data from the 1990s suggesting a rate of 3.8%. A review of Medline literature suggests the total rate of patients expressing feelings of doubt or regret is estimated to be as high as 8%. In a 2001 study of 232 MTF patients who underwent GRS with Dr. Toby Meltzer, none of the patients reported complete regret and only 6% reported partial or occasional regrets. An issue reported by some is the inability to find sexual partners. Laws regarding changes to the legal status of transsexual people are different from country to country. Some jurisdictions allow an individual to change their name, and sometimes, their legal gender, to reflect their gender identity. Within the US, some states allow amendments or complete replacement of the original birth certificates. Some states seal earlier records against all but court orders in order to protect the transsexual's privacy. In many places, it is not possible to change birth records or other legal designations of sex, although changes are occurring. Estelle Asmodelle’s book documented her struggle to change the Australian birth certificate and passport laws, although there are other individuals who have been instrumental in changing laws and thus attaining more acceptance for transsexual people in general. Medical treatment for transsexual and transgender people is available in most Western countries. However, transsexual and transgender people challenge the "normative" gender roles of many cultures and often face considerable hatred and prejudice. The film Boys Don't Cry chronicles the case of Brandon Teena, a transsexual man who was raped and murdered after his status was discovered. The project Remembering Our Dead, founded by Gwendolyn Ann Smith, archives numerous cases of transsexual and transgender people being murdered. In the United States, November 20 has been set aside as the "Day of Remembrance" for all murdered transgender people. Some people who have switched their gender role enter into traditional social institutions such as marriage and parenting. They sometimes adopt or provide foster care for children, as complete sex reassignment therapy inevitably results in infertility.Some transsexual people have children from before transition. Some of these children continue living with their transitioning/transitioned parent, or retain close contact with them. Health-practitioner manuals, professional journalistic style guides, and LGBT advocacy groups advise the adoption by others of the name and pronouns identified by the person in question, including present references to the transgender or transsexual person's past. Family members and friends who may be confused about pronoun usage or the definitions of sex are commonly instructed in proper pronoun usage, either by the transsexual person or by professionals or other persons familiar with pronoun usage as it relates to transsexual people. Sometimes transsexual people have to correct their friends and family members many times before they begin to use the transsexual person's desired pronouns consistently. Deliberate mis-gendering is perceived[by whom?] to be a form of transphobia. Both "transsexualism" and "gender identity disorders not resulting from physical impairments" are specifically excluded from coverage under the Americans with Disabilities Act Section 12211. Gender dysphoria is not excluded. Transsexual people can have difficulty maintaining employment. Most find it necessary to remain employed during transition in order to cover the costs of living and transition. However, employment discrimination against trans people is rampant and many of them are fired when they come out or are involuntarily outed at work. Transsexual people must decide whether to transition on-the-job, or to find a new job when they make their social transition. Other stresses that transsexual people face in the workplace are being fearful of coworkers negatively responding to their transition, and losing job experience under a previous name—even deciding which rest room to use can prove challenging. Finding employment can be especially challenging for those in mid-transition. Laws regarding name and gender changes in many countries make it difficult for transsexual people to conceal their trans status from their employers. Because the Harry Benjamin Standards of Care require a one-year RLE[clarification needed] prior to SRS, some feel this creates a Catch 22 situation which makes it difficult for trans people to remain employed or obtain SRS. In many countries, laws provide protection from workplace discrimination based on gender identity or gender expression, including masculine women and feminine men. An increasing number of companies are including "gender identity and expression" in their non-discrimination policies. Often these laws and policies do not cover all situations and are not strictly enforced. California's anti-discrimination laws protect transsexual persons in the workplace and specifically prohibit employers from terminating or refusing to hire a person based on their transsexuality. The European Union provides employment protection as part of gender discrimination protections following the European Court of Justice decisions in P v S and Cornwall County Council. In the National Transgender Transgender Discrimination Survey, 44% of respondents reported not getting a job they applied for because of being transgender. 36% of trans women reported losing a job due to discrimination compared to 19% of trans men. 54% of trans women and 50% of trans men report having been harassed in the workplace. Transgender people who have been fired due to bias are more than 34 times likely than members of the general population to attempt suicide. Some transsexual men and women choose to live completely as members of their gender without being public about their past. This approach is sometimes called stealth. Some people feel that they have an obligation to be open about their past in order to further the cause of civil rights for LGBT people. There are examples of people having been denied medical treatment upon discovery of their trans status, whether it was revealed by the patient or inadvertently discovered by the doctors. For example, Leslie Feinberg was once turned away from a hospital emergency room where he had sought treatment for endocarditis.[unreliable source?] Feinberg was presenting as a man but had female genital anatomy. He nearly died after being denied treatment. Feinberg's case demonstrates one of the many dangers of having one's trans status discovered. Tyra Hunter died after being denied care by paramedics and emergency room physicians after she was injured in an automobile accident. In the media Transsexualism was discussed in the mass media as long ago as the 1930s. The American magazine Time in 1936 devoted an article to what it called "hermaphrodites", treating the subject with sensitivity and not sensationalism. It described the call by Avery Brundage, who led the American team to the 1936 Summer Olympics in Berlin, that a system be established to examine female athletes for "sex ambiguities"; two athletes changed sex after the Games. Before transsexual people were depicted in popular movies and television shows, Aleshia Brevard — an actual transsexual whose surgery took place in 1962 — was actively working as an actress and model in Hollywood and New York throughout the 1960s and '70s. Aleshia never portrayed a transsexual person, though she appeared in eight Hollywood produced films, on most of the popular variety shows of the day including The Dean Martin Show, and was a regular on The Red Skelton Show and One Life to Live before returning to University to teach Drama and Acting. Thomas Harris's Silence of the Lambs included a serial killer who considered himself a transsexual. After being turned down for sex reassignment surgery due to not meeting necessary psychological evaluations, he then harvested female bodies to make a feminine suit. In the novel, it is noted that the character is not actually a transsexual; this distinction is made only briefly in the film. Films depicting transgender issues include: Come Back to the Five and Dime, Jimmy Dean, Jimmy Dean, The World According to Garp, The Adventures of Priscilla, Queen of the Desert, All About My Mother and The Crying Game. The film Different for Girls is notable for its depiction of a transsexual woman who meets up with, and forms a romantic relationship with, her former best friend from her all-male boarding school. Ma Vie en Rose portrays a six-year-old child who is gender variant. The film Wild Zero features Kwancharu Shitichai, a transsexual Thai actor. When the main character is conflicted about falling in love with a "woman who is also a man", Guitar Wolf tells him "Love knows no race, nationality or gender!" Although Better Than Chocolate is primarily about the romance of two lesbians, a subplot in the 1999 Canadian film has Judy (Peter Outerbridge), a trans woman with a crush on Frances (Ann-Marie MacDonald), the owner of a lesbian bookstore. Within the film has a few scenes showing how Judy loses her parents who are unable to accept her, and buy her off with a bye forever present in purchasing a home for her. Southern Comfort is a 2001 documentary by filmmaker Katie Davis, which follows the final months of the life of Robert Eads, a female-to-male transsexual living in Georgia. Eads was diagnosed with ovarian cancer and rejected for treatment by over two dozen doctors due to his transsexuality. The documentary follows Eads and several of his closest friends, a support group of transsexual southerners known as "Southern Comfort". The documentary won several awards, including the Grand Jury Prize at the Sundance Film Festival, First Prize at the Seattle International Film Festival, and the Special Audience Award at the Berlin Film Festival. Two notable films depict transphobic violence based on true events: Soldier's Girl (about the relationship between Barry Winchell and Calpernia Addams, and Winchell's subsequent murder) and Boys Don't Cry (about Brandon Teena's murder). Calpernia Addams has appeared in numerous movies and television shows, including the 2005 movie Transamerica, in which Felicity Huffman portrays a transsexual woman. In fall 2005, the Sundance Channel aired a documentary series known as TransGeneration. This series focused on four transsexual college students, including two trans women and two trans men, in various stages of transition. In February 2006, Logo aired Beautiful Daughters, a documentary film about the first all-trans cast of The Vagina Monologues, which included Addams, Lynn Conway, Andrea James, and Leslie Townsend. Also in 2006, Lifetime aired a movie biography on the murder of "Eddie"/"Gwen" Araujo called A Girl Like Me: The Gwen Araujo Story. Transsexual people have also been depicted in popular television shows. In part of the first season of the 1970s t.v. comedy series, Soap, Billy Crystal plays Jodie Dallas, a gay man who is about to undergo a sex change in order to legally marry his male lover, who breaks off the relationship just before the surgery. In Just Shoot Me!, David Spade's character meets up with his childhood male friend, who has transitioned to living as a woman. After initially being frightened, he eventually forms sexual attraction to his friend, but is scorned, as he is 'not her type'. In an episode of Becker Dr. Becker gets an out-of-town visit from an old friend who turns out to have undergone SRS, it plays out very similar to the situations in Just Shoot Me!. In a 1980s episode of The Love Boat, McKenzie Phillips portrays a trans woman who is eventually accepted as a friend by her old high school classmate, series regular Fred Grandy. In the 1970s on The Jeffersons, George's Navy buddy Eddie shows up as Edie and is eventually accepted by George. Dramas including Law & Order and Nip/Tuck have had episodes featuring transsexual characters and actresses. While in Nip/Tuck the role was played by a non-transsexual woman, in Law & Order some were played by professional cross-dressers. Without a Trace and CSI: Crime Scene Investigation have had episodes dealing with violence against transsexual characters. Many transsexual actresses and extras appeared on the CSI episode, "Ch-Ch-Changes," including Marci Bowers and Calpernia Addams. The trans woman victim, Wendy, was played by Sarah Buxton, a cisgender woman. Candis Cayne, a transsexual actress, appeared in CSI: NY as a transsexual character. From 2007 to 2008, she also portrayed a transsexual character (this time recurring) in the ABC series Dirty Sexy Money. "Coronation Street" once had a transsexual woman named Hayley, who was Harold in her childhood. She died on 20 January 2014. Since 2004, with the goal of crowning the top transsexual of the world, a beauty pageant by the name of The World's Most Beautiful Transsexual Contest was held in Las Vegas, Nevada. The pageant accepted pre-operation and post-operation trans women, but required proof of their gender at birth. The winner of the 2004 pageant was a woman named Mimi Marks. Jenna Talackova, the 23-year-old woman who forced Donald Trump and his Miss Universe Canada pageant to end its ban on transgender contestants, competed in the pageant on May 19, 2012 in Toronto. On Saturday, January 12, 2013, Kylan Arianna Wenzel was the first transgender woman allowed to compete in a Miss Universe Organization pageant since Donald Trump changed the rules to allow women like Wenzel to enter officially. Miss Wenzel was the first transgender woman to compete in a Miss Universe Organization pageant since officials disqualified 23-year-old Miss Canada Jenna Talackova last year after learning she was transgender. Transgender researcher and activist Prempreeda Pramoj Na Ayutthaya claims that there is notable discrimination against transsexual people in relation to education and job opportunities in Thailand. An article in Bangkok Post in 2013, claims that there is societal discrimination against transsexuals in Thailand. An editorial in Bangkok Post in 2013, said "Yet it is also true that we don't find transgenders as high-ranking officials, doctors, lawyers, scientists, or teachers in state-run schools and colleges. Nor as executives in the corporate world. In short, the doors of government agencies and large corporations are still closed to transgender women. It is why they must be self-employed or work as freelancers." Thai law does not give "post-operation" male-to-female transexual people—who are government employees—the right to wear female uniforms at work. In 2013 Bangkok Post said that Jetsada "Note" Taesombat, coordinator of the Thai Transgender Alliance, "believes it is crucial for transgender men and women to be legally recognised as part of society. At present, they are legally identified as their sex at birth. 'Transgender men and women also want the civil partnership law to pass, since gender recognition is the most important issue. To legalise same-sex civil partnerships would mean that we, as people with sexual diversity, can finally be recognised legally. The most important thing for me and for everyone is to be accepted as part of society,' Note says." A 2014 Bangkok Post article said that a Mayathom 1 [grade school] textbook had been criticized for discrimination and lack of gender sensitivity, because the textbook denoted transgender people as gender confusion—khon long pate, and illustrations in the textbook "feature performances by transgender dancers". The word long "has negative connotations. Transgender or kham pate is more suitable". It was reported that Officials at the Education Ministry would look into the matter. A 2014 Bangkok Post article said that LGBT "still face discrimination affecting their social rights and job opportunities", according to a report by US Agency for International Development—and the United States Development Programme". Furthermore LGBT "still face difficulty gaining acceptance for non-traditional sexuality, even though the tourism authority has been promoting Thailand as a gay-friendly country". Furthermore "transgendered people cannot change identity papers, and male-to-female transgender people still have to perform military service". Furthermore "examples of inequality among LGBT" include the case of "a hospital which refused to allow a transexual to stay in a woman's ward, even though she had undergone sexual reassignment surgery". (The report was "prepared and researched over two years", and it "is part of the project, 'Being LGBT in Asia'—a project also held "in Cambodia, China, Indonesia, Mongolia, Nepal, the Philippines, Thailand and Vietnam".) History and other cultures A number of Native American and First Nations cultures have traditional social and ceremonial roles for individuals who do not fit into the usual roles for males and females in that culture. These roles can vary widely between Nations, because gender roles, when they exist at all, also vary considerably among different Native cultures. However, a modern, pan-Indian movement among LGBT Natives, known as Two-Spirit, has emerged in recent years. Customs and traditions Transgender Day of Remembrance The Transgender Day of Remembrance is held every year on November 20. This event is held in honor of Rita Hester (killed Nov. 28, 1998), a victim of an anti-transgender hate crime. TDOR serves a number of purposes: - memorializes all of those who have been victims of hate crimes and prejudice - raises awareness about hate crimes towards the transgender community - honor the lost ones and their relatives by expressing respect for each other The Trans March is one of three protests held in San Francisco, California during "Pride Weekend" during the last weekend of June. Every year people from the transexual community gather in San Francisco, CA to protest social justice and equality for them. In addition, through the march they strive to inspire everyone from the transexual community to come out to an environment where power is shared and where one can feel safe and cared for. The event also hosts comedians, music, and dancing at the park. After parties are often followed after the event. All About Trans All About Trans is an organization in the UK whose goal is to influence and improve media professionals' understanding and portrayal of transsexual people. They do this by connecting media outlets with members of the transsexual community throughout the UK in order to foster a greater sensitivity toward this group of people. Paris Lees works as a facilitator with this organization and was recognized on The Independent on Sunday's Pink List in 2013 for being the most influential figure in the LGBT community in the UK. Transgender At Work Transgender At Work (TAW) is an organization with a focus on addressing issues in the workplace for transsexual individuals. Its goal is to allow transsexual employees to work productively without feeling as if they must hide an essential part of themselves. This includes addressing such issues as transsexual individuals being excluded from employer health care on the basis of their transsexuality. National Transgender Advocacy Coalition The National Transgender Advocacy Coalition is a lobbying organization in the United States dedicated to preserving the civil rights of transsexual individuals. It began in Virginia in 1999 and held its first lobbying event in 2001. It has no paid employees, but consists of a board of experienced lobbyists and activists. Renaissance Education Association The Renaissance Education Association is a non-profit organization founded in Pennsylvania that is dedicated to providing education and social support regarding transgender issues. This includes providing educational programs, support groups, and resources to community care providers. It also strives to provide personal and educational resources for individuals struggling with issues related to transsexuality and those close to them. Survivor Project is a non-profit organization founded in 1997 that is devoted to assisting intersex and transsexual survivors of domestic and sexual violence. This is done through caring action and education. The Project provides presentations, workshops, and consultation materials to many communities and universities across the United States. It also works to find information regarding the specific issues faced by intersex and transsexual individuals who are victimized. Empowering survivors and allowing them to participate in anti-violence activism is one major philosophy of the organization. Transgender Law and Policy Institute The Transgender Law and Policy Institute (TLPI) was founded by Paisley Currah, Associate Professor of Political Science at Brooklyn College. It is dedicated to engaging in effective advocacy for transgender people in our society. The TLPI brings experts together to work on law and policy initiatives designed to advance transgender equality. Their website provides information and resources on legislation, case law, employer and college policies and other resources.They also work with the Gay & Lesbian Advocates & Defenders (GLAD) in New England. Trans*topia is section of Youth Resource (a project of Advocates for Youth, a nonprofit organization located in Washington D.C.) designed for the needs of transsexual youth. Their website includes articles about being young and transgender, both personal accounts and scientific articles that are intended to help transgender youth become more informed and comfortable with their sexuality and gender. - List of transgender-related topics - List of transgender-rights organizations - List of LGBT-related organizations - List of transgender people - "ICD-10". 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Retrieved 2007-08-03. - Godbout, Louis (2004). "Elagabalus". GLBTQ: An Encyclopedia of Gay, Lesbian, Bisexual, Transgender, and Queer Culture. Chicago: glbtq, Inc. Retrieved 2007-08-06. - Gilley, Brian Joseph (2006: 8). Becoming Two-Spirit: Gay Identity and Social Acceptance in Indian Country. ISBN 0-8032-7126-3. - "About TDOR at Transgender Day of Remembrance". Transgenderdor.org. 1998-11-28. Retrieved 2011-07-06. - "San Francisco Trans March \| SF's premiere transgender Pride event, Friday, June 22, 2012". Transmarch.org. Retrieved 2011-07-06. - "Paris Lees: From prison to transgender role model". BBC News. 2013-10-27. - Burns, Christine: Why Phrasebook Diversity is not Enough (Press for Change) - Brown, Mildred L.; Chloe Ann Rounsley (1996). True Selves: Understanding Transsexualism – For Families, Friends, Coworkers, and Helping Professionals. Jossey-Bass. ISBN 978-0-7879-6702-4. - Feinberg, Leslie (1999). Trans Liberation : Beyond Pink or Blue. Beacon Press. ISBN 978-0-8070-7951-5. - Standards of Care for Gender Identity Disorders, Sixth Version. – World Professional Association for Transgender Health (2001) - Kruijver, Frank P. M.; Jiang-Ning Zhou, Chris W. Pool, Michel A. Hofman, Louis J. G. Gooren and Dick F. Swaab (2000). "Male-to-Female Transsexuals Have Female Neuron Numbers in a Limbic Nucleus". Journal of Clinical Endocrinology & Metabolism 85 (5): 2034–41. doi:10.1210/jc.85.5.2034. PMID 10843193. - Schneider, Harald J.; Johanna Pickel, Günter K. Stalla (2006). "Typical female 2nd–4th finger length (2D:4D) ratios in male-to-female transsexuals-possible implications for prenatal androgen exposure". International Society of Psychoneuroendocrinology 31 (2): 265–9. doi:10.1016/j.psyneuen.2005.07.005. PMID 16140461. - Xavier, J., Simmons, R. (2000) – The Washington transgender needs assessment survey, Washington, DC: The Administration for HIV and AIDS of the District of Columbia Government - Rathus, Spencer A.; Jeffery S. Nevid, Lois Fichner-Rathus (2002). Human Sexuality in a World of Diversity. Allyn & Bacon. ISBN 978-0-205-40615-9. - Pepper, Shanti M.; Peggy Lorah (2008). "Career Issues and Workplace Considerations for the Transsexual Community: Bridging a Gap of Knowledge for Career Counselors and Mental Health Care Providers". The Career Development Quarterly 56 (4): 330–343. doi:10.1002/j.2161-0045.2008.tb00098.x. \|Look up transsexualism in Wiktionary, the free dictionary.\| - Full service information and interactive dialogue for transsexual people - Asociación Española de Transexuales. AET Transexualia - Basic TG/TS/IS Information – including Successful Transwomen and Successful Transmen - FTM International – Female To Male International: practical and medical information - FTM Australia – Comprehensive information for all men identified female at birth in Australia. - Hudson's FTM Resource Guide – Comprehensive information for female to male trans men and allies – US-based - Gender.org – The home of Gender Education & Advocacy, a nonprofit corporation using the web to provide education and advocacy for transsexual and transgender issues. - Definition and Synopsis of the Etiology of Adult Gender Identity Disorder and Transsexualism – prepared by 24 internationally recognized experts, published by the Gender Identity Research and Education Society (GIRES)(See: http://www.gires.org.uk) - The International Journal of Transgenderism – The Official Journal of the World Professional Association for Transgender Health (formerly HBIGDA). An archive of IJT Volumes I through V is available, as are several books on transsexualism, including Harry Benjamin's "The Transsexual Phenomenon" - TransParentcy – supports transgender parents and their advocates (lawyers, mental health professionals, friends, family) by providing information and resources. - Transsexual Road Map – consumer information and advice for transsexual women. - Lynn Conway's transsexual resources pages - "Dr. Anne Lawrence On Transsexualism and Sexuality" - detailed information on medical aspects of transition - The Gender Identity Research and Education Society	2	51	8	0	0	0	0.792143	8	14,530
* To whom correspondence should be addressed. Received May 17, 2001; Revision received July 10, 2001 Cadherins are a family of membrane receptors that mediate calcium-dependent homophilic cell-cell adhesion. Cadherins play a key role in the regulation of organ and tissue development during embryogenesis. In adult organisms, these proteins are responsible for formation of stable cell-cell junctions and maintenance of normal tissue structure. Disruption in expression or function of cadherins may cause uncontrolled cell migration and proliferation during tumor development. This review focuses on the structure and physiological functions of classical cadherins. KEY WORDS: cadherins, cell-cell adhesion, morphogenesis, signaling, oncogenesis STRUCTURE OF CLASSICAL CADHERINS The majority of members of the cadherin superfamily are transmembrane glycoproteins that pass the membrane only once. The N- and C-termini of the cadherin protein chain are located outside and inside the cell, respectively (Fig. 1). The extracellular portion of the cadherin molecule consists of a varying number of so-called cadherin domains that are highly homologous to each other. Each domain is comprised of approximately 110 amino acid residues . Classical cadherins contain five cadherin domains that are commonly designated as EC1-EC5 (beginning with the N-terminus of the molecule). The conformation of the cadherin molecule is stable only in the presence of Ca2+, whose binding with the extracellular portion of the polypeptide chain is prerequisite for cadherin-mediated cell-cell adhesion. Calcium-binding sites consisting of short highly conserved amino acid sequences are located between neighboring extracellular repeats . The cytoplasmic domain of classical cadherins is associated with the cytoplasmic proteins catenins, which, in turn, serve as intermediate linkers between the cadherins and actin filaments [10-12]. It is this cadherin-catenin complex that is required for providing normal cell-cell adhesion. In principle, extracellular cadherin domains per se are capable of homophilic recognition and binding. It was shown that cells that express mutant cadherins lacking the cytoplasmic domains can bind with substrate covered with purified cadherin ectodomains. However, in this case adhesion is much weaker than in the case of cells bearing full-size cadherins [11, 13, 14]. These data indicate that the formation of stable cell-cell junctions depends on the presence in the cadherin molecule of functionally active cytoplasmic domain and association of the latter with the cytoskeleton. As mentioned above, cadherins mediate homophilic adhesion: during co-culturing of different types of cells, those cells first aggregate that bear identical cadherins on their surfaces . Similar dependence between cell sorting in the developing tissues and expression of different cadherins in them is observed during embryogenesis . The extracellular domains (primarily, the N-terminal domain EC1) play a key role in homophilic recognition between two cadherin molecules. It was shown that cells expressing chimerical E-cadherin, in which the EC1 domain was substituted with EC1 domain of P-cadherin, did not recognize the cells bearing native E-cadherin and aggregated with the P-cadherin-expressing cells . The site responsible for homophilic recognition contains 40 amino acid residues located in the C-terminal region of EC1. Blashchuk et al. assumed that sequence His-Ala-Val located in the C-terminal region of domain EC1 plays a key role in the interaction between cadherins because synthetic peptides containing this sequence effectively blocked mouse embryo blastomere assembling (a process that is mediated by cadherins). However, later it was shown that homophilic recognition also requires the presence of other regions located in the N-terminal domain. In addition, it was discovered that the sequence His-Ala-Val is contained only in the molecule of classical cadherins of type I that involves E- (epithelial), N- (neural), P- (placental), VE- (vascular endothelial), and R- (retinal) cadherins. The corresponding regions of type II classical cadherins that involve recently discovered cadherins designated by numbers 5-12 contain other amino acid residues [9, 10]. Type I and II cadherins also differ from each other in some amino acid residues. Fig. 1. Structure of classical cadherins and their interaction with cytoplasmic proteins . It should be noted that some cadherins can also mediate weak heterophilic interactions. In particular, E- and N-cadherin can bind with the integrin alphaEbeta7 and receptor for fibroblast growth factor [20, 21], respectively. The role of the four other cadherin repeats (EC2-4) in the cell-cell interaction remains obscure. Possibly, only EC1 domain directly participate in homophilic binding, whereas the remaining domains act as spacers providing the required distance between the junction and cell surface. Nevertheless, they are required for cadherin-dependent adhesion: in the absence of other extracellular domains, the N-terminal domain alone cannot maintain functional binding or adhesive activity . Numerous data that has accumulated to date show that the extracellular cadherin fragments exist in the form of stable parallel lateral dimers. Lateral dimers were revealed by X-ray analysis of N-cadherin EC1 domains and E-cadherin fragments including EC1 and EC2 domains . The existence of dimers was also shown for the whole extracellular fragment of C-cadherin . In the same experiments, it was also shown that the ability of C-cadherin monomers to aggregate significantly decreases compared to the dimers. To date, the mechanism of dimer formation is poorly understood. Apparently, N-cadherin dimers are stabilized by the hydrophobic interactions between the monomers , whereas in the case of EC1-EC2 fragment of E-cadherin dimeric structure is maintained by Ca2+ . It is still unclear why dimers exert higher activity than monomers during cell-cell interaction. Two main views on this phenomenon exist. The first hypothesis proposes that dimers are bivalent, which increases their avidity. The second hypothesis implies that dimer formation is associated with the occurrence of a unique site ensuring homophilic binding, which is absent from the monomers. The mechanism of interaction of cadherin dimers located on the membranes of different cells has been also the subject of much controversy. Based on the results of X-ray analysis of NCD1, Shapiro et al. proposed the existence of a zipper-like self-assembling structure. This molecular zipper model (Fig. 2) logically explains the mechanism whereby numerous weak bonds can ensure highly efficient binding in the cell layer. However, some authors believe that cadherin zipper is an in vitro artifact and suggest an alternative hypothesis that was formulated based on the results of electron microscopic analysis of adhesive zone preparations obtained by the freeze-fracture method . Separate protein cylinders extending from one cell surface to another and binding with the similar structures on the neighboring cell are seen on the images. According to the second model, cadherin molecules (dimers or oligomers) act as discrete units and do not form zipper-like ordered structures on the cell surface . Fig. 2. Two models of cadherin molecular organization in adhesive junctions. The molecular zipper model based on the results of X-ray analysis of N-cadherin EC1 domain is shown on the left. The model of cylindrical oligomers based on the results of electron microscopy of zonula adherens preparations obtained by the freeze-fracture method is shown on the right . The conclusion that cadherin complexes interact with the cytoskeleton was first made based on the data that cadherins cannot be extracted with non-ionic detergents that effectively solubilized other membrane proteins [13, 25, 26]. It was shown later that the major cytoplasmic proteins associated with the cytoplasmic domain of cadherins and participating in cell adhesion are alpha- and beta-catenins, which mediate the interaction between the cadherins and actin cytoskeleton [11, 13, 25, 27-30]. The catenin-binding site was mapped on E-cadherin. It is located at the distance of 56 amino acid residues from the C-terminus of the molecule [25, 31]. Biochemical analysis with the use of purified catenins and recombinant cytoplasmic domain of cadherins [32, 33] and expression of beta-catenin deletion mutants [34-36] showed that beta-catenin directly binds to the cytoplasmic cadherin fragment and serves as a linker for alpha-catenin attachment. The crucial role of the cytoplasmic domain of cadherin (and the catenin-binding site, in particular) is corroborated by numerous experiments. It was shown that deletion of the cytoplasmic domain or the catenin-binding site suppresses stable cadherin-mediated adhesion of cultured cells [11, 13]. Alternatively, overexpression of the catenin-binding site in the cultured cells , Xenopus laevis embryos , or in the intestinal cells of transgenic mice also entails disruption of cell-cell junctions. Such unusual, at first glance, result (at least, in the case of Xenopus laevis) can be, apparently, explained by competition of the expressed catenin-binding site with the endogenous cadherin for catenin binding. The evidence for participation of alpha-catenin in cell adhesion was obtained on lung carcinoma cell culture that does not contain alpha-catenin and aggregates with each other very weakly despite the presence of cadherins on the cell surface. However, transfection with alpha-catenin cDNA restores cadherin-mediated adhesion in these cells [27, 29]. Rim et al. showed that alpha-catenin directly binds to actin filaments both in vitro and in vivo in the cultured cells. The actin-binding protein alpha-actinin contained in adhesive junctions apparently also interacts with alpha-catenin . Participation of beta-catenin in cell adhesion was confirmed in experiments on Drosophila embryos using mutation analysis of protein armadillo, a homolog of beta-catenin . beta-Catenin is attached to the cytoplasmic domain of cadherin via its central region containing so-called armadillo repeats [34, 36]. These repeats (40 amino acid resides each) were first described in protein armadillo in Drosophila [40, 41]. alpha-Catenin binds to the N-terminus of beta-catenin [32, 34-36]. The role of a linker between cadherin and alpha-catenin is apparently the only function of beta-catenin in cell adhesion. It was shown that a chimerical molecule where the cytoplasmic domain of E-cadherin is substituted with alpha-catenin ensures cell adhesion in the absence of beta-catenin as successfully as the whole protein complex . Plakoglobin (gamma-catenin) sometimes substitutes beta-catenin in the cadherin-catenin complex . However, its physiological role is not completely understood. Plakoglobin is the major component of the desmosomes , where it is associated with the desmosomal cadherins [44, 45]. The high extent of homology of plakoglobin to beta-catenin and armadillo [26, 46] implies that these proteins may have similar functions. However, mouse embryo cells lacking beta-catenin due to genetic recombination aggregate very weakly and readily dissociate despite the presence of plakoglobin in them . This is indicative of inability of plakoglobin to completely substitute for beta-catenin in cell adhesion. Deletion of the plakoglobin gene, which was also caused by homologous recombination, entails lethal changes in the heart structure and early death of the embryos, presumably due to disruptions in desmosomal junction formation . Other cytoplasmic proteins directly associated with cadherin are tyrosine phosphatases [49, 50] and the substrate for src-kinase p120cas [51-53]. Interestingly, the level of cadherin expression in the cell may affect catenin expression. Transfection of L-cells with E-, N-, or P-cadherin cDNA results in a significant increase in the catenin content without changing the catenin mRNA content. Hence, the presence of cadherins regulates catenin expression at the post-translation level . It was also reported that cadherin cytoplasmic domain may mediate adhesion independently of catenins. Chimerical cadherin molecules in which cadherin cytoplasmic domain was substituted for the analogous domain of desmoglein-3 (one of desmosomal cadherins) that cannot bind catenins, mediates cadherin-dependent adhesion in the cultured cells . Thus, association with catenins is not the only way of participation of the intracellular cadherin domain in cell-cell adhesion. CELL-CELL JUNCTIONS CONTAINING CADHERINS Immunohistochemical analysis of tissues and cultured cells shows that cadherins most often are constituents of cell-cell adhesive junctions (Fig. 3). This type of junctions involves autotypic junctions between the layers of the same glial cell in the axon myelin sheath ; adhesive junctions in synapses, where cadherins link pre- and postsynaptic membranes in the regions adjacent to the neurotransmitter secretion areas [57, 58]; the intermediate disks between the cardiomyocytes ; and some other. The best-known type of cell-cell adhesive junctions is zonula adherens located at the apico-lateral border of the epithelial layer a little lower than the tight junctions. Actin bunches attached to the adhesive junctions girding the cell on the cytoplasmic side are located parallel to the membrane surface and form a united contracting network in the epithelial layer. Assembling of the belt-like zonula adherens is apparently the basis for the occurrence of the epithelial morphology of the cell layer [60-63]. During morphogenesis, folding of the epithelial layers into tubes is often attained by contraction of actin filaments contained in the zonula adherens, which is associated with narrowing the apical end of each cell in the apical layer and results in the cell layer bending [64, 65]. Besides cadherins and catenins, adhesive junctions contain numerous proteins (such as vinculin, ezrin, moesin, and radixin), protein components of the actin cytoskeleton, and integral membrane proteins (e.g., epidermal growth factor receptor, EGF) . Genetic studies on Drosophila revealed other components required for adhesive junction assembly. In particular, the genes whose mutations lead to disruptions in the course of zonula adherens assembling were identified in studies on Drosophila embryos. They involve the gene of beta-catenin homolog, armadillo, which is completely consistent with the view on the key role of this protein in cadherin-mediated adhesion [30, 67], as well as the genes crumb and stardust [67-69]. It was shown that gene crumb encodes the integral membrane protein that is required for epithelization of the ectodermic cells. In mutant individuals with inactive crumb gene normal cadherin-catenin complexes are expressed on the cell surface; however, their distribution is chaotic, leading to disruption in formation of mature zonula adherens in the epithelium [68-70]. Fig. 3. Cell-cell junctions formed by cadherins: a) epithelial zonula adherens; b) intermediate disks between the cardiomyocytes; c) adhesive junctions restricting the area of neurotransmitter secretion in the synapse; d) autotypic junctions between the glial cell layers in axon myelin sheath . It should be noted that in many cells cadherins can mediate adhesion without formation of morphologically pronounced adhesive junctions. Even in the epithelium of some organs, where cell-cell adhesion depends on E-cadherin, zonula adherens is absent . Cadherin-mediated adhesion without cadherin accumulation in the adhesive junctions was also described for blastomeres , nerve ridge cells , and fibroblasts transfected with different types of cadherins . REGULATION OF CADHERIN ACTIVITY Cadherin-mediated adhesion can be regulated by a variety of extracellular signals, including growth factors [72-74], peptide hormones [75, 76], signals from gap junctions , and cholinergic receptor agonists . In response to these external stimuli, different signals are generated in the cell, of which protein phosphorylation is, apparently, the most important for the regulation of cadherin function . Protein kinase C (PKC) participates in the activation of E-cadherin-dependent mouse embryo cell compacting, which was demonstrated with the use of a combination of pharmacological agonists and antagonists. Embryo compacting is accelerated by the addition of PKC-stimulating agents (e.g., phorbol ester and diacylglycerol) and inhibited by PKC-blocking agents , the PKC effect being blocked by the addition of anti-E-cadherin antibodies. However, it was not determined which PKC-mediated way is activated in this case. Using a similar experimental approach, a potential inhibitory effect of tyrosine phosphorylation on cadherin function was shown. Several scientific groups discovered that enhancement of tyrosine phosphorylation (transfection with v-src or incubation of the cells with pervanadate) weakens cadherin-mediated cell-cell adhesion. Components of the cadherin-catenin complex (primarily beta-catenin) undergo tyrosine phosphorylation in response to v-src transfection and incubation with pervanadate [80-82]. Attenuation of adhesion in these experiments was blocked by herbimicin, which is also indicative of participation of tyrosine phosphorylation in the regulation of cadherin activity. It was also shown that v-src can affect cadherin-mediated adhesion irrespective of beta-catenin . The authors of this work used mutant E-cadherin that could directly bind with the C-terminal fragment of alpha-catenin and induce adhesion without the participation of beta-catenin. However, in this case transfection with v-src also significantly inhibited cell-cell adhesion. Other data confirming the effect of tyrosine phosphorylation on cadherin-dependent adhesion are known. Tyrosine phosphorylation of beta-catenin is observed when cells are treated with hepatocyte growth factor (HGF) and EGF (agents that can induce dissociation of epithelial cells) . Tyrosine kinases or their substrates can associate with the cadherin-catenin complex. It is known that p120cas, a member of the armadillo protein family, is a substrate for both src kinases and receptor tyrosine kinases . It was shown that p120cas directly binds to the distal part of the cytoplasmic domain of E-cadherin, forming a whole complex with cadherin and beta-catenin or plakoglobin [52, 53, 84, 85]. Activation of the Erb-2/Neu receptor tyrosine kinase in the epithelial cells causes disassembling of the cell-cell junctions formed by E-cadherin, which results in the loss of the epithelial phenotype by the cells . EGF receptor tyrosine kinase also can bind to the cadherin-catenin complex . In addition, it was shown that cadherin-catenin complex can interact with receptor-dependent tyrosine phosphatases [49, 50, 88]. Cadherin function may also be affected by cell-cell communication via gap junctions. Inhibition of cell-cell communication by expression of the chimerical protein connexin 32/connexin 43 inhibitor (a protein that forms gap junctions) in Xenopus embryo cells leads to blastomere separation. A similar effect is observed when mutant cadherin is expressed in the embryo cells. This phenotype can be corrected by coexpression of connexin 37 that is insensitive to the inhibitor . Similarly, cell-cell junction assembling in Novikov hepatoma cells is suppressed by anti-connexin and anti-cadherin antibodies . The mechanism of signal transduction mediated by the gap junctions remains obscure. It is assumed that in this case cadherin-dependent adhesion and cell-cell junction assembling may be regulated via temporal increase in the concentration of Ca2+ and other small signal molecules (such as cyclic nucleotides or inositol phosphate) penetrating through the gap junctions and activating the intracellular processes that affect cadherin activity. The strength of cell-cell interactions can be affected both by modulating cadherin activity and changing their expression level in the cell. It was demonstrated that an increase in cadherin content enhances cell adhesion [7, 90, 91]. It was also shown that cadherin expression in cultured cells is regulated by growth factors and peptide hormones [72, 73, 75, 76]. Another mechanism of regulation of cadherin activity is changing the extent of clustering of cadherin molecules in the junction area. As was mentioned above, lateral clustering of cadherin molecules can significantly affect the strength of cell-cell interaction. Changes in the extent of clustering can mediate rapid changes in cell adhesion strength. For example, mouse embryo blastomere compacting is associated with E-cadherin redistribution in the region of cell-cell junctions without any change in protein expression . CADHERINS AND SIGNALING To date, numerous data indicate that cell adhesion receptors can affect cell form, motility, and growth not only due to mechanical attachment of the cells to each other or to the substrate, but also by activating internal signaling . Some papers report that many effects of cadherin on cell behavior are rapid and apparently caused by a series of short-term signals rather than by assembling stable long-term cell-cell junctions [4, 6, 94]. However, until recently only indirect evidence of cadherin ability to induce the production of secondary messengers in the cell have been known. For instance, it was shown that axon outgrowth stimulated by N-cadherin is associated with changes in the cytoplasmic Ca2+ concentration and activation of G-proteins and tyrosine kinases. However, it was not clear whether these signals result from the direct interaction of N-cadherin molecules [95, 96]. Because different signal molecules (such as proteins belonging to the non-receptor src kinase family as well as some membrane receptors and phosphatases) were found in the cell-cell junctions of epithelial cells [49, 97, 98], it was suggested that these molecules can mediate cadherin-dependent signaling. Data on the direct effect of cadherins on the signal processes appeared only during the last two years. It was shown that inter-cadherin junctions in cultured fibroblasts induced oscillations in the cytoplasmic Ca2+ concentration, antibodies raised against the first domain EC1 mimicking this effect. The oscillations occurred in the regions of cell-cell interactions and coincided in time with translocation of actin and other cytoplasmic proteins into the adhesive complexes . N-Cadherin can regulate axon outgrowth by direct interaction with the EGF receptor, thereby activating the cascade of mitogen-activated protein kinases (MAPK) . The experiments on cultured keratinocytes showed that adhesive junction formation leads to a rapid activation of MAPK-dependent signaling and that this effect is mediated by E-cadherin. In addition, E-cadherin can stimulate MAPK by ligand-independent activation of EGF receptors . It also activates Cdc42, a low-molecular-weight GTPase belonging to the Rho family, which regulates the cytoskeleton structure . For a long time beta-catenin, whose signal activity is well known, was considered as a candidate for the role of a messenger of signal transduction from cadherins, with which it is associated. beta-Catenin and its homolog armadillo from Drosophila are components of Wnt/wingless signal pathway that plays a key role in embryogenesis [102-104]. Recent data, however, indicate that the interaction between beta-catenin and cadherins is not prerequisite for manifestation of its signal activity. It was also shown that beta-catenin function as a cadherin partner during adhesive junction formation is not directly associated with its signal function in the cytoplasm and/or nucleus, where it affects transcription of genes by interacting with specific transcription factors [36, 105-111]. Free beta-catenin content in the cytoplasm is regulated by the protein product of the APC (adenomatous polyposis coli) gene. Formation of the complex between these two proteins is a signal for beta-catenin degradation. Conversely, triggering the Wnt signal pathway results in beta-catenin stabilization, its accumulation in the cytoplasm, and binding to the transcriptional factor Tcf, which, in turn, stimulates transcription of some genes. On the other hand, although the adhesive and signal functions of beta-catenin are separated, the formation of cell-cell junctions can apparently indirectly affect beta-catenin-dependent signaling. It was shown that overexpression of cadherins in the embryos of Xenopus laevis and Drosophila inhibited signal transduction via beta-catenin/armadillo [106, 112]. In Xenopus embryos, the inhibition is due to beta-catenin binding with C-cadherin on the inner surface of the cell membrane. As this takes places, beta-catenin is removed from its cytoplasmic pool, becoming inaccessible for participating in signaling. Thus, cadherins can regulate beta-catenin signaling activity by changing its distribution in the cell. It cannot be ruled out, however, that cadherins indirectly contribute to signaling regulation. Approaching of the membranes of the neighboring cells during adhesive junction formation may enable the interaction of membrane receptors and their membrane-bound ligands on the neighboring cells and activate juxtacrine signaling. This hypothesis is corroborated by data on association of some signal molecules with the cadherin-catenin complexes and on high concentration of tyrosine kinase substrates in the regions of adhesive junctions. The group of juxtacrine receptors described to date involves notch, delta, sevenless, and bride-of-sevenless (boss) receptors participating in Drosophila embryogenesis [113, 114] and associated with the membrane form of tumor necrosis factor (TNF) and transforming growth factor (TGFalpha) . It is tenable to assume that signaling via such receptors depends on the proximity of the surface of adjacent cells and, respectively, on formation of inter-cadherin junctions. This hypothesis is confirmed by the fact that expression of cadherins in the fibroblasts entails communication enhancement via gap junctions . THE ROLE OF CADHERINS IN MORPHOGENESIS The formation of tissues and organs during embryogenesis is determined by a number of processes coordinated in time and space, such as cell aggregation, polarization, differentiation, and migration. Because cell-cell and cell-nuclear matrix adhesive junctions play a key role in all these events, adhesion receptors are often called morphoregulatory molecules. One such adhesion-dependent processes is selective cell segregation. This phenomenon was discovered as early as in the 1950s. In classical works in embryology, it was shown that suspended cells from different amphibian blastophylla are capable of homotypic reaggregation to form junctions only with similar cells in correspondence with their histogenetic origin . Later it was discovered that this homotypic aggregation is based on selective expression of specific adhesion molecules on different subpopulations of cells. The role of cadherins in this process was revealed by Nose et al. . The L-cells were transfected with cDNA of either E- or P-cadherin. The suspensions were then mixed in vitro and analyzed for cluster formation. Under these conditions, highly selective adhesion between cells expressing cadherins of the same type was observed. Another morphogenetic process in which cadherins play a key role is cell condensing (i.e., transition of cell population from dispersed state to condensed solid formation). An example of such condensing is blastomere assembling at the early stages of embryogenesis. E-Cadherin plays a crucial role in cell condensing in mouse embryo morula: the embryo structure is disrupted as a result of treatment of the cells with blocking anti-E-cadherin antibodies, introduction of antisense nucleotides to E-cadherin mRNA into the cell, and in transgenic mice defective by the gene encoding this protein [118-123]. Injection of antisense nucleotides into Xenopus laevis oocytes, which decreases expression of EP-cadherin (a Xenopus laevis protein homologous to E- and P-cadherins), significantly attenuates adhesion between the blastomeres and entails disruption of the embryo structure . Numerous studies performed both in intact embryos and cultured cells revealed significant correlation between epithelization of mesenchymal cells and expression of specific cadherins in them. During somite development, mesenchymal cells comprising its future wall are polarized and temporarily form epithelium-like structures, the expression of N-cadherin in them significantly increasing [64, 65, 125]. Transfection of cultured mesenchymal cells with cDNA of different cadherins results in their epithelization [13, 126-128], whereas inhibition of cell-cell interactions by anti-cadherin antibodies leads to the loss of epithelial phenotype by the cells and stimulates cell motility and invasiveness [129-131]. One of the most vivid examples of participation of cadherins in morphogenesis is their role in the central nervous system development. At different stages of embryogenesis and in different structural layers, neuroepithelial tissues express more than 20 different cadherins involved in all key events of neurogenesis, beginning from selective aggregation of the cells at the earliest stages of embryo development and finishing with the formation of synapses [132-137]. Cadherins play a key role during neuroectoderm sorting and neural tube formation. It was also shown that before segregation of the neuroectoderm from the ectoblast in neurula, a coordinated decrease in the expression of E-cadherin and increase in that of N-cadherin occurs in the cells of future neuroectoderm. It is believed that it is N-cadherin that is responsible for selective cell uniting in the neural plate [64, 65, 138]. Interestingly, normal neural tube is formed in transgenic mice defective in the N-cadherin gene. Apparently, in this case N-cadherin is functionally substituted with other adhesion molecules (presumably, cadherin-6) . It is known that the coordinated change in the cell shape induced by microfilament contraction in zonula adherens underlies neural tube folding and other morphogenetic processes that require change in the shape of the epithelial layers [64, 65]. Further development of the neural tube involves its segregation to separate regions due to local expression of different cadherins. For example, selective distribution of E- and R-cadherins, cadherin-6, and cadherin-8 in different regions of embryonic brain is observed [135, 136, 140, 141]. The possibility of selective segregation of nerve cells that express cadherins of the same type was demonstrated in vitro. In vivo such segregation of the neural tube to segments apparently prevents the migration of nerve cells between adjacent regions of the developing brain . Normal expression of cadherins is required for neurite outgrowth activating and regulating. The expression of dominant-negative functionally inactive N-cadherin in developing frog retina blocks the axon and dendrite outgrowth. Those axons that are still formed are usually shorter and often do not have growth cones . In the experiments in vitro, it was shown that growth and migration of axons change during neuron culturing on the substrates containing recombinant cadherins. In particular, recombinant N-cadherin enhances adhesion of axons to the substrate and enables their projecting in the direction of higher concentrations of the recombinant protein. Similar growth stimulation is observed when the neurons are cultured on the monolayer of cells transfected with N-cadherin cDNA [8, 95, 143-146]. Such effect on axon projecting is apparently due to the interaction of N-cadherin with FGF receptor with subsequent MAPK activation . By contrast, another member of the cadherin family, T-cadherin, inhibits axon outgrowth [137, 147]. Thus, the coordinated action of different cadherins and other adhesion receptors expressed on the axon membrane and surrounding tissues ensure navigation of axon projecting to the peripheral targets. Cadherins also play a key role in setting and stabilization of junctions between the neurons and formation of neural nets and neuromuscular junctions [148-153]. In mouse postnatal brain, cadherins of the same type are expressed in functionally related regions (e.g., in the thalamus nucleus and related cortex regions ). During chick eye development N-cadherin stabilizes the junctions between the axon termini and their targets. Formation of a branched net of neural termini in the retina may be blocked by injecting anti-N-cadherin antibodies . It was shown that in synapses cadherins anchor the pre- and postsynaptic membranes, bordering the area of neurotransmitter secretion [57, 58]. E-Cadherin is also present in the myelin sheath of nerves, where it forms autotypic adhesion junctions between the plasma membrane layers of the same Schwann cell (Fig. 3). CADHERINS AND ONCOGENESIS The ability of tumor cells for uncontrolled growth, migration, invasion into surrounding tissues, and metastasizing is often associated with disruption of cell-cell and cell-extracellular matrix junctions [156, 157]. For this reason, special attention is currently paid to identification and characterization of cell adhesion receptors involved in tumor development. With regard for the role of cadherins in cell-cell adhesion, maintenance of tissue structure, and regulation of epithelial cell phenotype, it was assumed that the disruption of cadherin-dependent cell-cell interactions in the epithelium may cause attenuation of cell-cell junctions, loss of epithelial phenotype, enhancement of cell motility, removal of contact suppression of growth, and, as a result, uncontrolled proliferation and invasion of tumor cells . The majority of studies in this area focus on the role of E-cadherin in malignant cell transformation. In many works, it has been shown that E-cadherin expression is decreased or absent from different carcinomas (esophagus, stomach, or breast) [159-162]. Abnormal distribution of E-cadherin in tumor cells was often observed (it was absent from the regions of adhesion junctions). It should be noted that E-cadherin expression was most often decreased in the undifferentiated aggressive carcinomas that have high invasive potential . Similar results were obtained on cultured cells. Frixen et al. also reported that carcinoma cell lines with the epithelial noninvasive phenotype expressed E-cadherin, whereas the latter was absent from the cells with the fibroblastoid phenotype. Navarro et al. revealed reciprocal dependence between the amount of E-cadherin expressed on the cell surface of different carcinomas and the ability of these cells for invasion. Malignant transformation of MDCK epithelial cells (which are noninvasive in normal state) as a result of injection of Harvey and Maloney sarcoma virus to the cell culture is accompanied by a decrease in E-cadherin expression on the cell surface. A similar change of MDCK cell phenotype from noninvasive for invasive is also observed after disruption of cell-cell junctions in the presence of anti-E-cadherin antibodies . Conversely, transfection of the carcinoma cells with E-cadherin cDNA restores normal cell phenotype, decreases invasiveness and migration, and suppresses tumor growth [163-165]. The few studies on the role of P-cadherin in oncogenesis also revealed a correlation between decreased expression of this protein and the invasiveness of lung carcinomas and melanomas . Unexpected results were obtained when studying the effect of N-cadherin on tumor cells. It was discovered that expression of this protein is significantly enhanced in invasive undifferentiated breast carcinoma cells . It was also shown that an increase in N-cadherin expression in the carcinoma cells simultaneously with the decrease in E- and P-cadherin expression changes the phenotype from epithelial to mesenchymal . Transfection of MCF-7 carcinoma cells with N-cadherin cDNA significantly enhances the invasiveness and stimulates metastasis development despite the presence of E-cadherin in these cells . Such an opposite effect of cell-cell adhesion mediated by E- and N-cadherins on cell behavior may be due to the ability of E-cadherin to form stable cell-cell junctions that prevent cell migration, whereas N-cadherin can form labile junctions required for such dynamic processes as axon projecting or migration and invasion of tumor cells . Other components of cadherin complexes (primarily catenins) can also affect the growth and migration of transformed cells. As was mentioned above (see Cadherins and Signaling), normal expression of free beta-catenin in the cytoplasm is maintained by the oncosuppressing protein APC that binds with excessive beta-catenin and activates its degradation . In patients with hereditary polyposis, who are predisposed to intestine cancer, mutations in the APC gene or directly in beta-catenin gene are often observed. As a result of these mutations, the APC protein lacks its ability to regulate beta-catenin level in the cytoplasm, which leads to uncontrolled activation of the Tcf transcription factor by beta-catenin and development of intestine tumors . T-CADHERIN IS AN ATYPICAL MEMBER OF THE CADHERIN FAMILY T-Cadherin (truncated) (or H-cadherin (heart), or cadherin-13) is one of the most unusual members of the cadherin superfamily. Although its N-terminal domain EC1 does not contain the His-Ala-Val sequence, its extracellular part comprised of five cadherin repeats is very similar in structure to the classical cadherins. A unique feature of this protein is the absence of both the transmembrane and cytoplasmic domains. It is anchored in the membrane via glycosylphosphatidylinositol (GPI) that attaches to the mature protein after cleavage its C-terminal sequence during processing in the endoplasmic reticulum . Despite the absence of the cytoplasmic domain, T-cadherin can mediate any weak homophilic adhesion of the suspended cells . The mechanisms of formation of cell-cell junctions via T-cadherin and classical cadherins are apparently significantly different because the majority of cadherins ensure adhesion only when they contain the cytoplasmic domain that mediates their binding with the cytoskeleton [11, 13]. Another unusual property of T-cadherin is simultaneous expression on the cell surface of its two forms (the mature protein and partially processed precursor containing an uncleaved propeptide, whose function remains obscure) . T-Cadherin was first discovered in chick nervous system [137, 175]. Later its human homolog called cadherin-13 was identified . The only physiological function of T-cadherin established so far is its participation in the regulation of neuron growth during embryogenesis. During formation of chick embryo hind limbs, the outgrowing axons avoid those regions where T-cadherin is expressed . Neuron culturing on substrate containing recombinant T-cadherin significantly inhibits axon growth . Contact suppression of axon growth as a result of homophilic binding between T-cadherin molecules located on the axon membrane and surrounding mesenchymal tissues is apparently a navigating mechanism whereby the direction of nerve fiber growth is determined. Numerous recent data indicate that malignant tumor development is associated with the changes in T-cadherin expression. The loss of chromosome 16q24 locus containing T-cadherin gene correlates with the development of pancreas, lung, stomach, and ovary cancers [177-182]. The transfection of tumor cells with T-cadherin cDNA entails a decrease in the proliferative and invasive activities both in vitro and in vivo as a result of challenging the mice with tumorigenic cell lines as well as the loss of cancer cell sensitivity to the action of growth factors . The mechanisms of T-cadherin effect on cell adhesion and proliferative activity are still unknown. It cannot be ruled out that the maintenance of mechanical junctions between the cells is not the main function of this protein. It is most likely that it serves as a signal receptor, a sensor that allows the cell to sense its environment. This hypothesis is corroborated by the data on T-cadherin distribution in the membrane: in the polarized intestinal cells it is located on the apical part of the cell rather than in the adhesive junctions on the basolateral cell surface . It has long being known that many other GPI proteins may activate intracellular signaling [186-188]. The absence of the cytoplasmic domain in these proteins implies the presence of a membrane adapter protein. Owing to the interaction with the latter, the signal can be relayed across the membrane from the GPI proteins into the cell. We showed that, similar to other GPI proteins, T-cadherin is located on the cell surface in special plasma membrane domains (caveolae and lipid rafts) , which also contain other signal molecules (such as G-proteins, src kinases, rasproteins, and transmembrane receptors of growth factors ). It cannot be excluded that some of these molecules may serve as messengers during activation of T-cadherin-dependent signaling. In our laboratory, the main attention is focused on investigation of the role that T-cadherin plays in the cardiovascular system function. Cell adhesion molecules play a crucial role in the maintenance of normal structure of vascular walls. The development of different pathologies (such as atherosclerosis and restenosis after balloon angioplasty and atherectomy) is characterized by enhanced migration, proliferation, and phenotypic modulation of the endothelial cells, which is often associated with disruption of cell-cell and cell-extracellular matrix junctions [191, 192]. The expression and functions of T-cadherin in the cardiovascular system have not been studied before. We performed a comparative study of T-cadherin expression in different human organs and tissues. The results show that T-cadherin content is maximal in the aorta, carotid, iliac, and kidney arteries, and in heart. In aorta wall, T-cadherin is contained in the endothelial and smooth muscle cells and pericytes. Its expression in the smooth muscle cells depends on the cell phenotype and proliferative activity [193-195] and increases in sclerotic lesion of vascular walls . Preliminary studies performed on the model of balloon catheterization of rat carotid artery indicate that T-cadherin expression in smooth muscle cells increases in restenosis. The content of this protein is also elevated in the endothelium isolated from tumor vasculature . In addition, anti-T-cadherin antibodies can affect the phenotype, adhesion, and motility of the endothelial cells in vitro (our unpublished data). With regard for these data, it is likely that T-cadherin plays a key role in the regulation of cell phenotype, migration, and growth, as well as in maintenance of vascular wall structure. Study of the interaction of heterophilic interactions between T-cadherin and blood plasma lipoproteins is also of great interest. Originally, the work of our group was aimed toward searching for the receptors that mediate the hormone-like effect of low-density lipoproteins on the systems of intracellular signaling in smooth muscle cells in human vasculature [197, 198]. On the surface of membranes of aorta smooth muscle cells, we discovered two unusual lipoprotein-binding proteins with molecular weight of 105 and 130 kD. The characteristics of these proteins are indicative of their participation in lipoprotein-dependent signaling [199, 200]. After isolation of these receptors from human aorta medium and determination of their amino acid sequence, we discovered that the 105-kD protein is mature T-cadherin , whereas the 130-kD protein is its partially processed precursor . It is known that increased lipoprotein content in blood plasma is a risk factor of development of vascular pathologies based on increased proliferation and migration of smooth muscle cells. 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Editor's note: For more on ACOs, get three experts' opinions in our new feature, Doctors in Dialogue. Over the past three decades, we have seen enormous advances in medical care as doctors have developed better ways to diagnose and treat patients. During the same time, there have been many changes in how that care is paid for and where it is delivered. Those of us who have lived through various iterations can be forgiven for our skepticism about any new “system” purported to revolutionize the delivery of health care. However, the newest acronym — ACO — stands for a concept that could represent a sea change in the very complex system of medical care that we have in our country. What Is an Accountable Care Organization? Accountable care organizations are groups of doctors, hospitals and other health care providers who join together to coordinate care for a group of patients. The purpose of an ACO is to reduce the cost of care by eliminating duplication of effort and testing, while increasing the quality of services. ACOs can be started by any health care entity, but at this point most are driven by hospitals or large groups of doctors. How Did ACOs Come About? The term “accountable care organization” was first used in 2006 by two doctors at a meeting of the Medicare Payment Advisory Committee.1 It was included in the 2010 health care reform law. In that legislation, Congress authorized CMS to contract with ACOs for groups of 5,000 or more patients. The ACO provides medical care to those patients and reports quality measures back to Medicare. The program is a “shared savings” model in the sense that, if the ACO is able to provide care for less money than Medicare would expect for that group of patients, and if the ACO meets certain quality measures, the ACO receives 50 percent of the savings, with Medicare keeping the remaining 50 percent. It is interesting and important to note that CMS has thus far refused to require patients assigned to an ACO to use only providers who are part of that ACO. In other words, patients assigned to an ACO can still choose any doctor or hospital for their care, and there is no penalty to them for their choice. Some ACOs have been disappointed by this decision, believing that they cannot be truly “accountable” for cost savings if patients can access any provider they choose. However, in the final rule implementing the section of the health care reform law that authorizes contracts with ACOs, CMS states, “We have also been vigilant in protecting the rights and benefits of fee-for-service beneficiaries under traditional Medicare to maintain the same access to care and freedom of choice that existed prior to the implementation of this program.”2 Clearly, CMS is committed to allowing patients to go to any provider, even if that policy reduces the ability of ACOs to control the cost of providing care. Under the current ACO provisions, doctors, hospitals and other providers will continue to be paid their normal reimbursements for the care they provide to ACO patients. Then, at the end of each contract year, Medicare will determine whether those payments have been less than expected for the enrolled population; if so, CMS will share the savings with the ACO, provided the quality reporting measures have been met. The ACO will have to decide how to distribute the savings among its providers. Why Did Congress Authorize CMS to Contract With ACOs? As someone once said, “It’s all about the money.” In 1960, less than 6 percent of our nation’s annual gross domestic product (GDP, the value of all goods and services produced in the United States) was spent on health care. In 2010, that figure was 17.9 percent,3 and if we project the growth curve into the future, it appears that health care expenditures could consume 50 percent of the U.S. GDP before the end of this century. All other countries spend significantly less per capita and less of their GDP on medical care: Switzerland, France and Germany are usually the next highest, with rates of around 11 percent of GDP. For these reasons, CMS is continually looking for ways to reduce the amounts spent on health care in the United States. There is a common view among health care leaders that about one-fifth of the expenditures made on health care in this country are due to complications from other care provided.4 If an ACO could reduce those costs, about $400 billion could be saved each year. In addition, coordination of care through an ACO could result in less duplication of services, especially testing, thereby saving billions more. Authorizing CMS to contract with ACOs was Congress’ way of pushing hospitals and other providers to work on coordinating care and improving quality to reduce overall health care expenditures. Although the health care reform law applies only to Medicare patients, many health insurance companies are following that lead and are looking at contracting with ACOs in hopes that their outlays for medical care can be reduced. What Is the Current Status of ACOs? Last December, CMS selected 32 organizations and designated them as “pioneers” in the ACO model. Those ACOs began their contracts on Jan. 1, 2012. In early April of this year, an additional 27 health systems were announced as having been selected for the program; they will serve about 375,000 Medicare beneficiaries in 18 states. In July an additional 88 ACOs were approved and CMS is currently reviewing another 100 ACO applications, so the program is off to an auspicious start.5 Because hospitals, doctors and insurers in the private health plan realm are also actively pursuing the principle ideas behind the ACO section of the health care reform law, every ophthalmology practice needs to pay attention to those developments. What Should Our Practice Do About ACOs? The main risk for ophthalmology practices from ACOs is loss of patients from an ACO that excludes their doctors from its panel. Although Medicare says patients will be able to stay with their current ophthalmologist even if they are assigned to an ACO, other doctors in the ACO will likely refer new patients to ophthalmologists who are members of the ACO. In addition, some private health plan–affiliated ACOs may employ financial incentives that make it difficult for patients to stay with their existing eye doctor. The bottom line is that your practice may need to have a “seat at the ACO table” so you can protect your access to patients. This means making sure that you are actively involved in ACO discussions in your local area and that you associate with the organization(s) that appear to have the best chance of success. In addition, having input into the ACO will help you influence its policies and payment distributions. There is another important consideration that is going to be a side effect of the move to ACOs. I was recently discussing ACOs with my internist, who is a partner in a large multispecialty clinic. He indicated that his practice is training its doctors to refer to specialists who control costs, provide quality care, get good outcomes and have low incidences of complications. They are doing this because they know that the time will come when their overall compensation will be significantly affected by the quality of care that their entire organization provides. It is critical that your practice pay close attention to the quality and costs of the service you provide, and it is a good idea to establish a regular program of patient surveys to ensure that you are serving patients in the way they desire. Patient satisfaction will undoubtedly be a factor in quality measurements for many ACOs. ACOs: A Sea Change or Just Another Forgotten Acronym? Only time will determine whether ACOs become a new way of doing business for health care providers or just another footnote in the history of health care reform attempts. However, the principles of improving quality, eliminating duplication and increasing efficiency to reduce the costs of health care are here to stay. Practices that excel in those areas will be in a much better position to thrive in the health care environment of the future. 1 Jordan T. Cohen, A Guide to Accountable Care Organizations, and Their Role in the Senate’s Health Reform Bill, March 11, 2010. 2 Federal Register, vol. 76, no. 212 (Nov. 2, 2011), p. 67804. 3 Centers for Medicare and Medicaid Services, Office of the Actuary, National Health Statistics Group; U.S. Department of Commerce, Bureau of Economic Analysis. 4 HealthLeaders Media, Align Physicians and Hospitals in a Non-Aligned World, 2012, p. 17. 5 Jenny Gold and Christian Torres, ACOs multiply as Medicare announces 27 new ones, Kaiser Health News, April 10, 2012. Issue Index \| Related Articles \| YO Info Archive * * * About the author: This article is an adaption of the original version, which appeared in the May 2012 AAOE Executive Update. It was written by Derek Preece, MBA, of BSM Consulting, a member of the AAOE Consultant Directory.	2	16	1	0	0	0	0.505386	1	1,866
Type 2 Diabetes Type 2 diabetes is a chronic disease in which your body is unable to maintain a normal blood sugar (glucose) level. - Birth Control Facts about birth control to help decide which type is right for you. - Type 2 Diabetes Basic facts about type 2 diabetes & risk factors to be aware of. - Binge Eating Disorder Facts about binge eating disorder, including symptoms and causes. - COPD Get the facts about chronic obstructive pulmonary disease (COPD), including symptoms and complications. - Chronic Idiopathic Constipation Learn about chronic idiopathic constipation, including treatment - Diabetic Macular Edema Facts about diabetic macular edema, including the different types. - Eating Disorders Facts about different types of eating disorders. - Flu Facts about influenza (flu), including symptoms and vaccines. - Food Allergy Facts about food allergy, including the symptoms and signs. - GERD Get the facts about gastroesophageal reflux disease (GERD). - View All Care Guides Prepare for your next visit with our extensive library of Care Guides Dr. Peter A Abaci has the following 2 specialties Anesthesiologists are physicians who are trained to administer anesthetics, which are medicines used to block nerve sensation. Anesthesia can be either local to one specific part of a body, like a tooth, or regional to block feeling to a larger portion of the body, such as during an epidural for child birth. It can also be more general to block sensation to the entire body, resulting in unconsciousness. Anesthesiologists assist in surgery by determining how much anesthesia is necessary and by monitoring the patient's level of responsiveness and vital signs throughout the procedure. The anesthesia specialist will also bring the patient out of anesthesia and then continue to monitor his or her vital signs post-operation. Besides assisting in surgeries, anesthesiologists may also treat patients suffering from chronic pain. - Pain Medicine - Chronic Pain - Cancer Pain - Complex Regional Pain Syndromes - Back Pain - Acute Pain See the board certifications this doctor has received. Board certifications provide confidence that this doctor meets the nationally recognized standards for education, knowledge and experience. Showing 5 of 7 Patients' Choice Award (2011, 2010) Patients' Choice recognition reflects the difference a particular physician has made in the lives of his/her patients. The honor is bestowed to physicians who have received near perfect scores, as voted by patients. Compassionate Doctor Recognition (2010) Compassionate Doctor certification is granted to physicians who treat their patients with the utmost kindness. The honor is granted based on a physician's overall and bedside manner scores. Dr. Abaci is affiliated (can practice and admit patients) with the following hospital(s). 23 Years Experience Keck School Of Medicine Of The University Of Southern California Graduated in 1995 Santa Clara Valley Medical Center Dr. Peter A Abaci accepts the following insurance providers. - Aetna Choice POS II - Aetna Managed Choice POS Open Access - Aetna Savings Plus of CA - Aetna Signature Administrators PPO BCBS Blue Card - BCBS Blue Card PPO Blue Cross California - Blue Cross CA PPO Prudent Buyer Small Group - Blue Cross CA Advantage PPO Preferred DirectAccess Plus - Blue Cross CA PPO Prudent Buyer Individual - Blue Cross CA PPO Prudent Buyer Large Group - Blue Cross CA Pathway X PPO - Blue Cross CA Select PPO Blue Shield California - BS CA Platinum 90 PPO - Blue Shield CA Bronze 60 PPO SHOP - Blue Shield CA Bronze Full PPO 4500 - Blue Shield CA PPO - Blue Shield CA Silver 70 PPO - CIGNA HMO - CIGNA LocalPlus - CIGNA Open Access Plus - CIGNA PPO - Health Net CA Individual and Family PPO - Health Net CA PPO - View by Location Locations & DirectionsBay Area Pain & Wellness Center, 15047 Los Gatos Blvd Ste 200, Los Gatos, CA Dr. Peter A Abaci is similar to the following 3 Doctors near Los Gatos, CA.	2	9	1	0	0	0	0.868144	1	901
National case definition: Plague Date of last revision/review: May 2008 Only confirmed cases of disease should be notified. Type of surveillance Routine case-by-case notification to the federal level Clinical evidence of illness with laboratory confirmation of infection: - isolation of Yersinia pestis from body fluids - a significant (i.e. fourfold or greater) rise in serum antibody titre to Y. pestis fraction 1 (F1) antigen by EIA or passive hemagglutination/inhibition titre Clinical evidence of illness with any of the following laboratory evidence: - demonstration of elevated serum antibody titre(s) to Y. pestis F1 antigen (without documented significant [i.e. fourfold or greater] change) in a patient with no history of plague immunization - demonstration of Y. pestis F1 antigen by immunofluorescence - detection of Y. pestis nucleic acid - > 1:10 passive hemagglutination/inhibition titre in a single serum sample in a patient with no history of vaccination or previous infection - detection of Y. pestis antibody by EIA Laboratory commentsSerologic confirmation is done by demonstration of a significant (i.e. fourfold or greater) rise in serum antibody titre to Y. pestis F1 antigen by EIA or passive hemagglutination/inhibition titre. Plague is characterized by fever, chills, headache, malaise, prostration and leukocytosis, and is manifest in one or more of the following principal forms: - Bubonic plague: regional lymphadenitis - Septicemic plague: septicemia with or without an evident bubo - Primary pneumonic plague: inhalation of infectious droplets - Secondary pneumonic plague: pneumonia, resulting from hematogenous spread in bubonic or septicemic cases - Pharyngeal plague: pharyngitis and cervical lymphadenitis resulting from exposure to larger infectious droplets or ingestion of infected tissues - ICD-10 code(s): A20.2 - ICD-9 code(s): 020.5 Type of international reporting Under Article 6 of the International Health Regulations (IHR) (2005), each State Party shall notify the World Health Organization (WHO) by way of the IHR National Focal Point,Footnote 1 and within 24 hours of assessment of public health information, of all events which may constitute a public health emergency of international concern within its territory in accordance with the decision instrument (Annex 2 of the IHRFootnote 2), as well as any health measure implemented in response to those events. - An event involving pneumonic plague shall always lead to the utilization of the algorithm in Annex 2 of the IHR, because it has demonstrated the ability to cause serious public health impact and to spread rapidly internationally. The need to notify any event involving plague to the WHO will depend upon the outcome of the assessment using the Annex 2 decision instrument. Note: If event does not meet the criteria for notification under Article 6 of the IHR, then other IHR-related reporting requirements may still apply with WHO and/or other States Parties, including those under Art. 7 (information-sharing during unexpected or unusual public health events), Art. 8 (consultation with WHO on public health events), Art. 9 (any public health risk that may cause international disease spread), Art. 10 (requests for verification from WHO), and Art. 44 (collaboration and assistance). Elimination or eradication efforts should be reported. Probable case definitions are provided as guidelines to assist with case finding and public health management, and are not for national notification purposes. - Case definitions for diseases under national surveillance. CCDR 2000;26(S3). Retrieved May 2008, from http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/00vol26/26s3/index.html - Centers for Disease Control and Prevention. Case definitions for infectious conditions under public health surveillance. MMWR 1997; 46(No. RR-10):25-6. - World Health Organization. Department of Communicable Disease Surveillance and Response (October 1999). WHO Recommended Surveillance Standards. 2nd ed. WHO/CDS/CSR/ISR/99.2. Retrieved May 29, 2007, from www.who.int/csr/resources/publications/surveillance/whocdscsrisr992.pdf - Dennis DT, Gage KL, Gratz N et al. Plague Manual. Epidemiology, Distribution, Surveillance and Control. WHO/CDS/CSR/EDC/99.2. Geneva: World Health Organization, 1999. - Prentice MB, Rahalison L. Plague. Lancet 2007;369:1196-207. - World Health Organization. International Health Regulations (2005). 3rd ed. Geneva, 2016, from http://www.who.int/ihr/publications/9789241580496/en/ Report a problem or mistake on this page - Date modified:	3	10	0	0	0	2	0.444823	2	1,082
Healthcare providers render care to patients in a number of clinical settings and document their services within a patient’s medical record. Beginning with the patient’s chief complaint, a doctor will assess the patient’s condition, review the patient’s past, family or social history; review the body’s organ systems with a series of questions, examine the patient, and determine the complexity of the medical decision making based on the presenting problems, diagnostic procedures ordered, and management options which can be as simple as ordering bed rest or as complex as dictating emergency major surgery. How Are Medical Coding and Billing Related? The medical billing process contains several steps that must be followed before submission of a claim – all of which encompass front desk procedures to the actual information within a medical record. Each step is important in the process, beginning with the initial phone call where a patient makes an appointment for an office visit: • What is the reason for the visit? • Does the patient have current insurance information on file? • Is the patient’s address current? Up-to-date patient information is mandatory or provided services will be unprocessable by an insurance carrier. Many providers choose to code their own services without fully understanding the complexities of coding. Coding problems exist without the basic knowledge of something as simple as recognizing the differences between CPT codes 90471 (Administration of a vaccine/toxoid) and 96372 (IM injection). Besides documenting the patient’s history, exam, and medical decision making, important coding questions must be addressed: • Did the physician document total time or suggest counseling or coordination of care as more than 50% of the visit? • Was face to face time in outpatient or inpatient setting indicated? • If smoking cessation counseling was provided, was time indicated? • Did the provider treat a problem unrelated to the patient’s annual exam? • Did the physician record how many times a nebulizer treatment was provided or if a vaccine that was given was actually paid for by the physician? • Was there a decision for surgery or was a visit billed for a different reason within a post-op global period? • Are late effects or manifestation diagnosis codes being indicated? Even if a provider codes his own work, medical billers and coders must often access records to ensure all services are captured. Medical coding is an exciting profession where medical records are analyzed and information is converted into numeric and alpha-numeric codes to be submitted to insurance companies for physician reimbursement. Understanding medical terminology and anatomy is important while studying for your CPC (Certified Professional Coder) credential as well. Because medical billers often appeal denied claims, it is becoming more of a trend for billers to learn coding to enhance their own profession. Both are challenging career choices that compliment one another. How Are Medical Coding and Billing Related Content: - Medical Coding Training - ICD 10 Training - Online Medical Billing and Coding Certification - Medical Coding Careers - Medical Coding Jobs - Medical Coding And Billing: AAPC Submit your review	3	3	2	0	0	0	0.478164	2	653
I. Acute Coronary Syndrome: What every physician needs to know. An acute coronary syndrome (ACS) is a constellation of symptoms and signs that result from obstruction of the coronary arteries. Common signs and symptoms include chest pain, dyspnea, and electrocardiographic abnormalities. The most common cause of acute coronary syndrome is blockage of the coronary artery from cholesterol rich plaque and thrombus. In acute coronary syndrome, a previously quiescent plaque has ruptured, exposing the lipid core, inciting platelet activation and aggregation with subsequent thrombus formation. When the atherothrombotic material is totally occlusive with complete cessation of blood flow through the artery, the acute coronary syndrome is termed ST-Elevation myocardial infarction (STEMI). If the occlusion is partially obstructive and there is no evidence of myocardial injury (e.g., elevated cardiac troponin), the ACS is termed unstable angina, but if cardiac injury is detected with a partial obstruction, then the term to describe the ACS is non-ST segment myocardial infarction (NSTEMI). ACS unrelated to plaque rupture can infrequently be seen from coronary vasospasm, embolization, or spontaneous coronary dissection. II. Diagnostic Confirmation: Are you sure your patient has Acute Coronary Syndrome? The diagnosis of ACS is based on finding a history compatible with active, obstructive coronary disease and supportive evidence based on ST segment deviation on ECG and evaluation of cardiac biomarkers (e.g., cardiac troponin, creatine kinase) suggestive of myocardial infarction. A. History Part I: Pattern Recognition: Typical patients with ACS will describe chest pain that is often located at the sternum and can be described as an ache or pressure. The textbook description is “an elephant sitting on my chest’ with the patient’s fist clenched over the sternum (classically referred to as the Levine’s sign). The chest symptoms classically last more than 20 minutes and may have increased in intensity, frequency, or duration recently. There may be radiation to the neck, jaw, back, or arms. There may be associated dyspnea, diaphoresis, and nausea. If significant myocardial pump dysfunction is present, the patient may report orthopnea or paroxysmal nocturnal dyspnea. It should be noted that these “typical features” are helpful if present but the absence does not exclude ACS. The symptoms may be localized to the epigastrium or there may be no chest symptoms at all. In fact, some or all of these findings may be absent, especially among elderly patients, women, and those with psychiatric disorders. The five most important factors from the initial history in the order of importance are (1) the nature of the anginal symptoms, (2) prior history of coronary artery disease (CAD), (3) sex, (4) age, and (5) the number of traditional risk factors present. For those with suspected ACS with prior history of heart disease, advanced age seems to be the most important risk factor (>55 years for males and >65 years for females). B. History Part 2: Prevalence: Acute coronary syndromes account for over 2.4 million discharges per year in the U.S. About 500,000 of these are for STEMI and the remainder are for NSTEMI or unstable angina. The risk factors for coronary artery disease increase the risk for ACS. These include hypertension, hypercholesterolemia, diabetes, smoking, advanced age, and a family history of premature coronary artery disease. These risk factors increase the risk for underlying atherosclerosis, the substrate for ACS. Several triggers for ACS have been implicated including: anxiety, emotional stress, strenuous exercise, influenza infection, and extreme physiologic stress due to concomitant medical or surgical illness. C. History Part 3: Competing diagnoses that can mimic Acute Coronary Syndrome. While the character of symptoms is often different from ACS, aortic dissection, pulmonary embolism, and pericarditis, with or without cardiac tamponade, should be considered. At times, pneumonia, pneumothorax, cholecystitis, peptic ulcer disease, and herpes zoster may be confused with ACS. D. Physical Examination Findings. The physical examination related to ACS is often nonspecific, but the complications associated with infarction and cardiac pump dysfunction may be manifest as tachycardia, bradycardia, hypotension, elevated jugular venous pressure, wheezes, crackles, or hepatomegaly. The heart examination may reveal right ventricular heave, sustained LV impulse, the presence of S3 and/or S4 as well as mitral regurgitation. Aortic regurgitation may suggest an aortic dissection. Diminished heart sounds raise the possibility of a pericardial effusion and/or tamponade physiology. Pulses should be examined as they may be asymmetric or exhibit bruits if there is preexisting vascular disease or if there is an aortic dissection, or if pulses are either diminished and delayed as seen in some cases of severe aortic stenosis. E. What diagnostic tests should be performed? A 12-lead ECG should be obtained and interpreted within 10 minutes of hospital triage, if not obtained by emergency medical services (EMS). A chest x-ray should be obtained if pneumonia or aortic dissection is suspected. If STEMI has been diagnosed, chest x-ray and laboratory results should not delay implementation of reperfusion therapy. 1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted? Cardiac specific troponin is the preferred biomarker to diagnose myocardial injury; however, these may be initially negative in STEMI patients presenting early and some NSTEMI patients. 2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted? A 12-lead electrocardiogram should be obtained and interpreted within 10 minutes of presentation. While imaging studies, such as stress testing with echocardiographic or nuclear imaging and coronary angiography, are used to assess risk during ACS, these studies are not used to make a diagnosis of ACS. Management of ACS is determined by the patient’s risk. In the case of ACS, to complete coronary occlusion, STEMI, the goal is for immediate revascularization to salvage myocardium. For NSTEMI and unstable angina (UA), treatment is to mitigate the changes of recurrent infarction and/or to reduce the size of infarction. Medical therapy is guided by the degree of patient risk for ischemic complications and balanced against the risk for bleeding or other complications from these treatments. If the patient is diagnosed with STEMI, the decision must be made as to whether fibrinolysis will be administered, primary percutaneous coronary intervention (PPCI) will be performed, or whether the patient will be transferred for primary PCI. Determination of PPCI vs. fibrinolysis for STEMI If PCI can be performed by skilled personnel in a timely fashion, door to balloon time <90 minutes, this is the preferable strategy for STEMI. If the patient is at a hospital where PCI is not performed, it is advisable to administer fibrinolysis if the delay related for transfer for PCI will exceed 60 minutes or if the total door to balloon time will exceed 120 minutes. If transfer can be arranged rapidly and PCI can be performed within 120 minutes from initial presentation, the patient can be transferred to the PCI capable hospital. It is advisable to transfer the patient to a PCI capable hospital routinely after administration of fibrinolysis in case the medication does not work or if there is recurrent infarction. A. Immediate management. As mentioned previously, the management of STEMI is emergent revascularization with fibrinolysis or preferably PPCI. Aspirin and unfractionated heparin or bivalirudin should be administered. Clopidogrel, ticagrelor, or prasugrel can be administered in addition to aspirin for STEMI. Early risk stratification is of paramount importance for patients presenting with NSTEMI/UA. Risk stratification tools, including the TIMI Risk Score for UA/NSTEMI and the GRACE risk score to help divide patients into low- or high-risk categories. Immediate management involves administration of oxygen and placement of IV access. Aspirin (162 to 325 mg) is administered orally or rectally. Analgesia with morphine may be administered while blood pressure and oxygenation are monitored. If possible, the patient should chew the aspirin to enhance absorption. An antithrombin should be selected for patients who are not low risk. Unfractionated heparin may be administered (50 units/kg up to maximum of 4000 units). Low molecular weight heparins (LMWH) have the advantage of fixed dosing that does not require monitoring, but should be avoided in patients who will be going on to coronary artery bypass grafting (CABG) surgery and in those with renal failure. Fondaparinux can be administered to patients who will be managed medically. Bivalirudin can be administered instead of UFH or LMWH. Additional antiplatelet therapy should be administered to high-risk individuals with NSTEMI. A loading dose of clopidogrel or ticagrelor can be administered in the emergency department for NSTEMI. Prasugrel should be administered in the catheterization laboratory if the patient requires PCI and clopidogrel or ticagrelor have not already been administered. Glycoprotein IIb/IIIa receptor antagonists are administered for high-risk individuals. Oral beta-blocker therapy should be administered within 24 hours of presentation unless there are signs of heart failure, there is evidence of a low output state, increased risk for cardiogenic shock, or other contraindications to therapy. An oral angiotensin converting-enzyme inhibitor (ACE-I) should be administered to those with left ventricular ejection fraction of ≤ 40%, without hypotension as defined by SBP <100 mm Hg or SBP >30 mm Hg below baseline, or shock, history of bilateral renal artery stenosis, or prior known allergy to ACEI. An angiotensin receptor blocker (ARB) may be used instead of an ACE-I if the patient is intolerant due to allergy or cough. Invasive therapy, cardiac catheterization, should be performed in patients whose procedural risk is not prohibitive, if that patient’s risk is not low. The angiogram allows for determination of whether medical therapy, CABG surgery, or PCI is the preferred management. For patients initially selected for conservative therapy, recurrent symptoms, hemodynamic instability, or the development of heart failure, should prompt coronary angiography. Angiography is usually performed on an urgent basis (within 48 to 72 hours) but should be performed sooner for those with symptoms refractory to medical therapy or in those who develop hemodynamic instability. Low-risk individuals should have a serial biomarker measurement. If these become elevated, an coronary angiography should be considered. For low-risk individuals whose biomarkers remain normal, further risk stratification can occur with stress testing. Pharmacologic testing can be used for those who cannot exercise. Imaging (echocardiography or nuclear imaging) should be added to the exercise ECG testing if the 12-Lead ECG exhibits ST segment abnormality or left bundle branch block. B. Physical Examination Tips to Guide Management. The patient should be monitored for the development of mechanical complications of infarction. The development of signs of congestion (S3, crackles, elevated JVP) or a new murmur should prompt further work-up and aggressive therapy. Patients with signs of confusion and lethargy may be developing cardiac insufficiency and this should be considered even if narcotics for pain have been administered. C. Laboratory Tests to Monitor Response To, and Adjustments in, Management. Complete blood count evaluating for anemia, leukocytosis, thrombocytosis, or thrombocytopenia should be obtained at baseline. Serum chemistries evaluating glucose, potassium, magnesium, bicarbonate, and renal function should be obtained at baseline for management of ACS. A lipid profile should be obtained, and for those with elevated blood glucose, glycated hemoglobin should be measured. Stool guaiac is often obtained to screen for occult blood. Serum creatinine, platelet count, and hemoglobin are monitored to assess for contrast-induced nephropathy, or bleeding complications or thrombocytopenia associated with anticoagulant, antiplatelet therapy, or procedures. D. Long-term management. Long-term management includes use of medications shown to be beneficial in the secondary prevention of atherosclerotic disease and congestive heart failure. These include reduction of blood pressure with a goal of 130/80 mm Hg and cholesterol reduction with an LDL cholesterol goal of <70 mg/dl. Patients should receive dual antiplatelet therapy with aspirin (75 mg to 100 mg QD) and either clopidogrel, ticagrelor, or prasugrel. The choice of the agent added to aspirin is somewhat dependent on the management strategy pursued in hospital and the optimal agent is a matter of debate. The duration of dual antiplatelet therapy is suggested by societal guidelines to be 12 months regardless of whether the patient was managed with medical therapy alone or revascularization using PCI or CABG surgery for ACS. Beta-blockers and ACE inhibitors are used particularly in those patients who are hypertensive or whose ejection fraction is reduced. The goal for glycated hemoglobin for diabetic patients is <7.0%. Patients should receive smoking cessation counseling and referral to cardiac rehabilitation. E. Common Pitfalls and Side-Effects of Management Cardiac specific troponin elevation may occur in situations besides ACS. Elevated cardiac biomarkers can occur in the setting of profound demand ischemia during noncardiac illness, and ACS should be diagnosed, and anticoagulant and invasive therapies implemented with caution in these settings. Nitrates should be avoided in those who have received phosphodiesterase III inhibitors for erectile dysfunction within 48 hours or those with SBP <90 mM Hg or >30 mm Hg below baseline and in those with a heart rate (HR) <50 beats/min or >100 beats/min in the absence of heart failure or right ventricular infarction. Prasugrel should not be administered to patients with prior transient ischemic attack (TIA) or stroke, and a lower dose should be considered for those <60 Kg or >75 years of age. Prasugrel should be held for 7 days prior to CABG; ticagrelor and clopidogrel should be held for 5 days prior to CABG, if possible. Abciximab should not be used for those who will not be undergoing PCI. Glycoprotein IIb/IIIa receptor antagonists can cause thrombocytopenia and unfractionated heparin can cause the heparin induced thrombocytopenic (HIT) syndrome. Eptifibatide, tirofiban, and enoxaparin should be dose adjusted for renal insufficiency. Intravenous beta-blockers given during the first 24 hours of ACS may be associated with adverse outcomes and should be reserved for those who are hypertensive and with ongoing symptoms. NSAIDS apart from aspirin and steroids should be avoided in ACS. Nitroglycerine 0.4 mg sublingually every 5 minutes up to 3 times. If chest pain persists, then 5 to 10 mcg/min titrating up 10 mcg/min every 10 minutes until chest pain free or SBP <100 mm Hg. Morphine 1 to 5 mg IV, repeat as tolerated Aspirin 162 to 325 mg orally or rectally initially, then 75 to 100 mg orally daily Clopidogrel 300 to 600 mg orally once, then 75 mg daily; may consider 150 mg orally daily for first 7 days of ACS. Prasugrel 60 mg orally once, then 10 mg orally daily; may use 5 mg orally daily for those <60 Kg or >75 years. Ticagrelor 90 mg orally once, then 180 mg orally twice daily Unfractionated heparin 50 U/kg IV up to 4,000 U, then 12 U/hr up to 1,000 U/hr IV Fondaparinux 2.5 mg subcutaneously daily up to 8 days Lovenox (UA/NSTEMI 1 mg/kg subcutaneously twice daily, dose adjust for GFR <30 cc/hr; STEMI 30 mg IV and 1 mg/kg subcutaneously twice daily if <75 years, if >=75 years, no bolus and 0.75 mg/kg subcutaneously twice daily if GFR <30 cc/min and <75 years then 30 mg IV and 1 mg/kg subcutaneously daily and if >=75 years no bolus and 1 mg/kg subcutaneously daily. Bivalirudin 0.1 mg/kg IV bolus then 0.25 mg/kg/hr IV for NSTEMI/UA and for PCI 0.75 mg/kg IV bolus (0.5 mg/kg IV if already on therapy) then 1.75 mg/kg/hr for duration of procedure or 4 hours thereafter. Reduce infusion rate to 1 mg/kg/hr if GFR <30 cc/min. Eptifibatide 180 mcg/kg IV twice followed by 2 mcg/kg/min IV; reduce to 1 mcg/kg/min if GFR is <50 cc/min Tirofiban 0.4 mcg/kg/min for 30 minutes then 0.1 mcg/kg/min; 0.2 mcg/kg IV bolus and 0.05 mcg/kg/min for patients with GFR <30 cc/min Abciximab 0.25 mg/kg IV bolus then 0.125 mcg/kg/min (up to 10 mg/min) IV. Management with Co-Morbidities Patients with impaired renal function, elderly patients, and women are at increased risk of bleeding complications from overdosing of medications and from invasive procedures. These patients should have close attention to dose adjustment, appropriate use of medications, and the appropriate use of invasive therapies. Patients should also be counseled on the importance of dual antiplatelet therapy to prevent recurrent MI and to prevent stent thrombosis if a stent was implanted during PCI. Patients should be counseled regarding the the importance of lifestyle modification of risk factors as well as medical therapy for secondary prevention. In particular, patients with ACS should be counseled on smoking cessation and the importance of exercise in addition to compliance with diet and prescribed medical therapy to improve secondary prevention. V. Patient Safety and Quality Measures A. Appropriate Prophylaxis and Other Measures to Prevent Readmission. Patients with ACS are often started on multiple medications. Appropriate patient education regarding the utility of each of these medications, anticipated side effects, and dangers of discontinuation should be emphasized. Patients should be counseled regarding what types of symptoms require reevaluation and follow-up with a cardiologist. The patient should be referred for cardiac rehabilitation. B. What's the Evidence for specific management and treatment recommendations? “2011 ACCF/AHA Focused Update incorporated into the ACC/AHA 2007 guidelines for management of unstable angina/non-ST-elevation myocardial infarction”. Circulation. vol. 123. 2011. pp. e426-e579. “Primary and secondary prevention of cardiovascular disease: Antithrombotic therapy and management”. Chest. vol. 41. 2012. pp. e637S-e668S. Bavry, AA, Kumbhani, DJ, Rassi, AN. ” Benefit of early invasive therapy in acute coronary syndromes: A meta-analysis of contemporary randomized clinical trials”. J Am Coll Cardiol. vol. 48. 2006. pp. 1319-25. C. DRG Codes and Expected Length of Stay. DRG 303 Coronary Artery Disease with Unstable Angina DRG 280 Acute MI discharged alive with major CC DRG 281 Acute MI discharged alive with CC DRG 282 Acute MI discharged alive without MCC/CC DRG 283 Acute MI expired with major CC DRG 284 Acute MI expired with CC DRG 285 Acute MI expired without MCC/CC Expected length of stay for uncomplicated ACS ranges from 1 day or longer depending upon the presence or absence of complications of therapy or the disorder. Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved. No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM. - I. Acute Coronary Syndrome: What every physician needs to know. - II. Diagnostic Confirmation: Are you sure your patient has Acute Coronary Syndrome? - A. History Part I: Pattern Recognition: - B. History Part 2: Prevalence: - C. History Part 3: Competing diagnoses that can mimic Acute Coronary Syndrome. - D. Physical Examination Findings. - E. What diagnostic tests should be performed? - 1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted? - 2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted? - III. Management. - A. Immediate management. - B. Physical Examination Tips to Guide Management. - C. Laboratory Tests to Monitor Response To, and Adjustments in, Management. - D. Long-term management. - E. Common Pitfalls and Side-Effects of Management - IV. Management with Co-Morbidities - V. Patient Safety and Quality Measures - A. Appropriate Prophylaxis and Other Measures to Prevent Readmission. - B. What's the Evidence for specific management and treatment recommendations? - C. DRG Codes and Expected Length of Stay.	2	34	0	2	0	0	0.892445	2	4,834
A ventilator is a device that supports or takes over the breathing process, pumping air into the lungs. Invasive and non-invasive ventilation differ in how the air is delivered to the person. In invasive ventilation, air is delivered via a tube that is inserted into the windpipe through the mouth or sometimes the nose. In NIV, air is delivered through a sealed mask that can be placed over the mouth, nose or the whole face. - Principle- Breathe in, Breathe out - What do ventilators do? - Types of ventilator - Top ventilator companies pumping air into the global medical industry - 5 Best ICU ventilator models in India (Updated-2021) - What are the essential parameters for configuring a ventilator? - Frequently Asked Questions (FAQs) Principle- Breathe in, Breathe out The principle function of a ventilator is to pump or blow oxygen-rich air into the lungs; this is referred to as “oxygenation”. Ventilators also assist in the removal of carbon dioxide from the lungs, and this is referred to as “ventilation”. What do ventilators do? A ventilator is a device that supports or recreates the process of breathing by pumping air into the lungs. Sometimes, people refer to it as a vent or breathing machine. Doctors use ventilators if a person cannot breathe adequately on their own. This may be because they are undergoing general anesthesia or have an illness that affects their breathing. There are many injuries and conditions that can cause respiratory failure, - head injury - lung disease - spinal cord injury - sudden cardiac arrest - neonatal respiratory distress syndrome - acute respiratory distress syndrome (ARDS) Some people with COVID-19 have severe difficulty breathing, or develop ARDS. However, this only occurs in people who become critically ill, which accounts for around 5% of all confirmed COVID-19 cases. There are different types of ventilator, and each provides varying levels of support. The type a doctor uses will depend on a person’s condition. Ventilators play an important role in saving lives, in both hospitals and ambulances. People who require long-term ventilation can also use them at home. Types of ventilator There are various ways a person can receive ventilator support. These include: - face mask ventilators - mechanical ventilators - manual resuscitator bags - tracheostomy ventilators Face mask ventilators are noninvasive, while mechanical and tracheostomy ventilators are invasive and work via tubes that a doctor inserts through a hole in the neck that leads to the trachea, or windpipe. Healthcare professionals term this intubation. In invasive ventilation, air is delivered via a tube that is inserted into the windpipe through the mouth or sometimes the nose. In non invasive, air is delivered through a sealed mask that can be placed over the mouth, nose or the whole face. Face mask ventilator A face mask ventilator is a noninvasive method of supporting a person’s breathing and oxygen levels. To use one, a person wears a mask that fits over the nose and mouth while air blows into their airways and lungs. People with COVID-19 may use a face mask ventilator if they are having difficulty breathing or do not have sufficient oxygen levels. Continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BiPAP) devices also operate via a face mask. People often use these for chronic conditions, such as chronic obstructive pulmonary disease, but some doctors, also use them for people with COVID-19. Mechanical ventilators are machines that take over the breathing process entirely. Doctors use these when a person cannot breathe on their own. Mechanical ventilators work via a tube in a person’s throat, pumping air into the lungs and transporting carbon dioxide away. A ventilator unit regulates the pressure, humidity, volume, and temperature of the air, depending on the controls that a doctor or respiratory therapist places. This allows healthcare professionals to control a person’s breathing and oxygen levels. Manual resuscitator bags Manual resuscitator bags are pieces of equipment that allow people to control the airflow of their ventilator with their hands. These devices consist of an empty bag, or “bladder,” that a person squeezes to pump air into the lungs. This can be useful as a temporary solution if a person on a mechanical ventilator needs to stop using it. For example, if there is a power outage, a person can use a manual resuscitator bag while waiting for the power to come back on. A tracheostomy is a procedure where a doctor creates an opening in the windpipe and inserts a tube, which allows air to flow in and out. This enables a person to breathe without using their nose or mouth. People who have undergone tracheostomies can also receive ventilator support through this opening. Instead of inserting a ventilator through the mouth, doctors insert it directly into the windpipe. Top ventilator companies pumping air into the global medical industry - Hamilton medical - Smiths Group 5 Best ICU ventilator models in India (Updated-2021) Philips V60 ICU Ventilator - AC Voltage : 100-240 VAC - AC Frequency : 50-60 Hz - Respiratory Rate : 0-90 BPM The Respironics V60 Ventilator combines Respironics’ ventilation expertise with Philips’ focus on simplifying advanced health care. The result is the noninvasive ventilation gold standard with an invasive ventilation safety net and an interactive display that helps simplify patient management. The Respironics V60 uses auto-adaptive technology to help ensure patient synchrony and therapy acceptance. Improved signal processing technology is finely tuned for both adult and pediatric patients. Product Features : • High resolution graphics facilitating waveform interpretation. • Internal 6-hour battery enables intra-hospital transport (actual battery time will vary depending on user settings and battery charge level). Standby mode supports patient-clinician interaction without nuisance alarms. • Data communication capabilities support hospital connectivity. • Respi-Link, a remote communication tool, allows efficient system diagnostics and upgrades via internet. • AVAPS maintains a target tidal volume in a pressure limited mode. It provides extra assurance similar to a volume limited mode with the safety of a pressure limited mode. • CPAP with C-Flex offers three levels of flow-based expiratory pressure relief. This option leads to improved sleep quality and patient comfort, adding greater flexibility and improved treatment acceptance. • PCV can be used when greater control of the patient’s breathing pattern is required. Additionally, the option of ventilating a patient invasively gives the caregiver greater flexibility in the approach to treatment. • ICU-grade NIV performance with enhanced safety and monitoring. Meditec England 1700 ICU Ventilator - Tidal Volume– 50 – 2500 ml - Respiratory rate– 2 – 80 bpm - Apnea Time– 2 – 60 sec - Nebulizer (time) – 10- 180 mins (3 Hours) The Meditec 1700 is designed to work in a highly versatile environment. Whether you need Invasive or Non Invasive ventilation the Meditec 1700 delivers. Power packed with a range of Ventilation modes to suit individual preferences the Meditec 1700 is ideal for use in an ICU, Intra-Hospital transport, Air and Ground transport. Simplicity, In-built air supply, versatility and affordable cost of ownership make Meditec 1700 the obvious choice. • Invasive as well as Non-Invasive Ventilation • Altitude compensation • Battery Backup: 3 Hours • Suitable with both dual as well as single limb breathing circuits • Touch screen as well as knob operated • Optional: EtCO2 & SpO2 Measurement • Inspiration hold: Measures patient’s lung compliance and resistance, Elasticity, Time constant • Nebulizer: 10–180 minutes • Key lock: Key & LCD Touch Screen Lock • Waveform freeze: Freezes the waveform Drager Savina 300 ICU Ventilator - Tidal Volume : 0.05 to 2.0 L, BTPS - Respiratory Rate : 0 -150 bpm - Power Supply : 100 V to 240 V, 50/60 Hz AC, 10 to 36 V DC The Drager Savina is an advanced, high-quality ICU ventilator that offers excellent ventilation performance combined with easy operation. Designed for both adult and pediatric ventilation, the Savina provides advanced therapy at any acuity level. • Intuitive Operating System • Scalable And Versatile Device • Combine Fully-featured • High-performance Ventilation With Infinity • Acute Care System Integration Philips (SH300) Control Oxygen Ventilator - Tidal Volume : 20-2500ml - Respiratory Rate : 0.1~12 S - Patient Age Group : Adult, Pediatric - Touch Screen Present : 10.4 TFT Touch Screen SH300 is an advanced ICU Ventilator for adults and pediatric with precise multi-ventilator modes, equipped with 10.4″ inch LCD screen in tilt angle for clear view and user-friendly operation • Perfect apnea ventilation technology, alarm system and backup battery • Pneumatically and electrically controlled • Applicable to adults and pediatric • Advanced flow trigger and traditional pressure trigger mechanism • Powerful monitoring function for multi-parameters displaying Hamilton- G5 ICU Ventilator - Maximum Inspiratory Flow :180 L/min peak flow - Recharge time: 7 hours - Oxygen Pressure : 2 to 6 bar / 29 to 87 psi - Oxygen Connector : DISS (CGA 1240) or NIST (optional) It’s designed for the most complex, critically ill patients in all ICU settings where lung protection is of paramount importance. The comprehensive monitoring package and state-of-the-art diagnostic tools for lung assessment support you in making the best possible clinical decisions for your patient. Heliox and high flow oxygen therapy, allows you to tailor the HAMILTON-G5 to fit the requirements of your ICU and meet the needs of each individual patient. • Automated control of the patient’s ventilation and oxygenation with INTELLiVENT-ASV • Real-time patient synchronization with IntelliSync+ • P/V Tool Pro for lung assessment and recruitment • Transpulmonary pressure measurement • High flow oxygen therapy • Adult, pediatric, and neonatal ventilation What are the essential parameters for configuring a ventilator? In order to set the different ventilation modes, it is important to be familiar with the fundamental characteristics of the device such as tidal volume and pressure. Here is a list of the main parameters required to configure a ventilator: - The tidal volume (TV) - Pressure (P): a distinction is made between inspiratory pressure (IP) and expiratory pressure (EP) - The inspiratory trigger - Inspiratory time - Respiratory rate - The I:E ratio (inhalation/exhalation), i.e. the ratio between inhalation and exhalation times Ventilators are devices that support a person’s breathing if they are experiencing respiratory failure. There are different types of ventilator, including noninvasive and invasive, that provide varying degrees of support. Demand for ventilators has increased due to COVID-19. It can take time to recover from being on a ventilator. Serious illness can impact physical and mental health. People experiencing persistent symptoms after weaning off ventilator support should seek guidance from a doctor. Frequently Asked Questions (FAQs) Q1. Can you breathe on your own on a ventilator? A ventilator mechanically helps pump oxygen into your body. The air flows through a tube that goes in your mouth and down your windpipe. The ventilator also may breathe out for you, or you may do it on your own. Q2. How do I choose a ventilator? Choosing mechanical ventilators should begin by defining the algorithms of how to ventilate a patient. Once this is done, a ventilator should allow the transformation of specific strategies into practice and the adaptation of the mechanical support to the needs of the individual patient. Q3. At what oxygen level do they put you on a ventilator? When oxygen levels become low (oxygen saturation < 85%), patients are usually intubated and placed on mechanical ventilation. For those patients, ventilators can be the difference between life and death. Q4. What is average time on ventilator? Most of the patients in the study spent an average of 10 days on a ventilator. Usually the average time a patient in an Intensive Care Unit (ICU) spends on a ventilator ranges from 3 to 7 days, according to one study. Q5. How much are ventilators machine cost? These full-featured ventilators are complex and expensive, costing from 2 lakh to 5 lakh and requiring dedicated software to administer high concentrations of oxygen to assist patients in respiratory distress.	2	18	0	0	0	2	0.533526	2	2,862
- Hemolytic-Uremic Syndrome (HUS) is a very rare disorder that primarily affects young children between the ages of one and 10 years, particularly those under the age of four years. Symptoms of Hemolytic-Uremic Syndrome usually become apparent three. — “CIGNA - Typical Hemolytic Uremic Syndrome”, - Definition of uremic in the Medical Dictionary. uremic explanation. Information about uremic in Free online English dictionary. What is uremic? Meaning of uremic medical term. What does uremic mean?. — “uremic - definition of uremic in the Medical dictionary - by”, medical- - uremia also uraemia n. A toxic condition resulting from kidney disease in which there is retention in the bloodstream of waste products normally Some uremic signs are due to losses of kidney function that do not involve azotemia. — “uremia: Definition from ”, - Atypical hemolytic-uremic syndrome is a disease that primarily affects kidney function. This condition, which can occur at any age, causes abnormal blood clots (thrombi) to form in small blood vessels in the kidneys. Atypical hemolytic-uremic syndrome is characterized by three major. — “Atypical hemolytic-uremic syndrome - Genetics Home Reference”, m.nih.gov - Uremic. Lifestyle, fitness & health information about Uremic. What Are the Causes of Acute Renal Failure in Children?, Kidney Disease Symptoms in Adults, What Causes Hemolytic uremic syndrome is a rare disease that primarily affects children under the age of ten and leads to acute renal failure. — “Uremic \| ”, - Detailed information on hemolytic uremic syndrome, including cause, progression, treatment, and statistics. — “Hemolytic Uremic Syndrome”, - Early symptoms include anorexia and lethargy, and late symptoms can include decreased mental acuity and coma. Renal failure (Acute renal failure, Chronic renal failure) · Uremic pericarditis · Uremia. — “Uremia - Wikipedia, the free encyclopedia”, - Uremic pruritus. FOLLOW UP. Given the typical histological ﬁndings from the skin biopsy in Uremic pruritus is often considered a misnomer for the. following reasons: pruritus in. — “Uremic pruritus”, uphs.upenn.edu - Uremic Frost. The Nephrology Blog. Monday, November 22, 2010. NEJM: The Frequent hemodialysis, as compared with conventional hemodialysis, was associated with favorable results with respect to the. — “Uremic Frost”, - Explains how hemolytic uremic syndrome develops after E-coli infection in the digestive tract and describes the treatments available. — “Hemolytic Uremic Syndrome in Children”, kidney.niddk.nih.gov - Hemolytic Uremic Syndrome (HUS) is a serious disease that affects the kidneys and blood clotting system. It is a rare disease but is more common in children, especially younger than age 5. — “Hemolytic Uremic Syndrome - Medpedia”, - What are the Symptoms of Uremic Poisoning? Answer: The term uremia was first used in 1847 to describe the symptoms of kidney failure. Nonetheless, the terms uremia or uremic poisoning have persisted, and now mean the symptoms that patients feel when they have kidney failure. — “What are the Symptoms of Uremic Poisoning? (Renalife)”, - Uremic definition, pertaining to uremia. See more. — “Uremic \| Define Uremic at ”, - Hemolytic Uremic Syndrome cases mostly are due to food poisoning by E. coli strain O157:H7. Research has not yet found the causes for the Hemolytic Uremic Syndrome occurrence in most of the patients. — “” - Introduction Background Richard Bright first described uremic pericarditis 163 years ago. causing 341 illnesses, including hemolytic uremic syndrome (HUS). HUS is not well described in non-O157 E coli. — “Uremic”, - Signs and symptoms of hemolytic uremic syndrome may include: Fever Abdominal pain Pale Hemolytic uremic syndrome (HUS) In children, most cases of hemolytic uremic syndrome. — “Uremic - Kosmix : Reference, Videos, Images, News, Shopping”, - Overview: Uremic neuropathy is a distal sensorimotor polyneuropathy caused by uremic toxins. The severity of neuropathy is correlated strongly with the severity of the renal insufficiency. Uremic neuropathy is considered a dying-back neuropathy. — “Uremic Neuropathy: eMedicine Neurology”, - Because an incubation period of approximately one week occurs between the start of diarrhea and the onset of hemolytic uremic syndrome, physicians should maintain a high index of suspicion; early laboratory testing is important to diagnose and manage this syndrome. — “Hemolytic Uremic Syndrome: An Emerging Health Risk”, - List of disease causes of Uremic encephalopathy, patient stories, diagnostic guides. Diagnostic checklist, medical tests, doctor questions, and related signs or symptoms for Uremic encephalopathy. — “Uremic encephalopathy - ”, - Definition of uremic in the Online Dictionary. Meaning of uremic. Pronunciation of uremic. Translations of uremic. uremic synonyms, uremic antonyms. Information about uremic in the free online English dictionary and encyclopedia. — “uremic - definition of uremic by the Free Online Dictionary”, - Read about hemolytic uremic syndrome (HUS), blood clotting disease caused by E. Coli infection, birth control pills, pneumonia, medications, and more. Symptoms, diagnosis, treatment and prevention information is included. — “Hemolytic Uremic Syndrome (HUS) Causes, Symptoms, Diagnosis”, related videos for uremic - Gastritis Uremic 98180 - Food Safety Attorney Bill Marler Explains E. coli O157 and HUS Video www.about- Food Safety Attorney Bill Marler Explains E. coli O157 Infection E. coli O157:H7 produces a toxin when it's in the human body that is excreted from the bacteria and if it enters the bloodstream can cause severe, severe illness. The normal illness that can be ascribed to E. coli O157 is Hemolytic Uremic Syndrome, or HUS and that has caused untold deaths and severe illness in the United States and frankly, throughout the world. Where is E. coli O157:H7? It is everywhere. It used to be thought of -- primarily still is -- as a reservoir in cattle, but we've been finding it in buffalo, sheep, goats, deer -- they even found it in a trout in a lake. These are bacteria that are fecal in origin, that come from animals other than us, and in our body...our body doesn't tolerate them. E. coli O157:H7 outbreaks can kill. E. coli and other bacteria are especially dangerous to the young and the elderly. Because in the young their immune system is not fully developed, and in the elderly their immune system has been compromised. What are the symptoms? E. coli O157 symptoms are pretty classic. Three to four days after the ingestion of the bacteria it's cramping that'll then turn to bloody diarrhea. Bloody diarrhea is a hallmark of E. coli O157:H7 infection. Most people recover. Some ninety percent of the people within ten days will start to get better, but it's a very horrible experience, and very painful. Five to ten percent of people will go on to develop ... - Gastroduodenoscopy on the cat , uremic gastritis - DIC, TTP, HUS - The Microangiopathic Anemias - Quinine Dangers! Night time leg cramps Quinine (kwye' nine) Last revised: July 1, 2010. ISSUE: Due to continued reports of serious side effects in patients using quinine (Qualaquin) ''off-label'' for night time leg cramps, FDA has approved a risk management plan to warn against the use of this drug for such unapproved uses. Quinine should not be used for night time leg cramps. Quinine use may result in serious and life-threatening hematological reactions, including serious bleeding due to thrombocytopenia, and hemolytic-uremic syndrome/ thrombotic thrombocytopenic purpura, which in some cases may result in permanent kidney damage. In some patients, adverse reactions result in hospitalization and death. - say prayer audition by jewelry sa audi para sa mga friends ko n sobra kong mahal miss ko kau lagi ^_^I LOVE YOU ALL guys, radshie, raize, uremic, mhondz, wiloma, athru, min3, ate honey, hibana, at sa lahat lahat ^_^ - E. coli Lawyer Bill Marler Explains Bologna E. coli Outbreak and Recall E. coli attorney Bill Marler of the Marler Clark, the nation's largest food poisoning law firm explains the recent Seltzer's Lebanon bologna E. coli outbreak and recall. The CDC, about a week ago announced an outbreak of E. coli O157:H7 linked to what's known as Lebanon bologna, which is a sausage, salami type of product primarily made in Pennsylvania and has sickened about a dozen people in five states, mostly on the East coast. There doesn't to be anyone who has developed Hemolytic Uremic Syndrome or kidney failure but there has been a couple of people hospitalized and about a dozen people sick. The real risk is to the very young and very old. This bologna outbreak seems to be striking people in the middle age range, which is why I think we're not seeing a lot of people hospitalized which is obviously a good thing. Sausage, salami, and bologna have had a history of problems over the last two decades with dozens of outbreaks of Salmonella, E. coli, Listeria and others. It is not heat cured. It is a low heat and they tend to use a lot of spices and things to deal with the bacterial growth. Anybody who has this product in their homes should discard it or contact the department of health or contact the company and ask for a refund. This kind of product is generally safe, but there was clearly in this instance some sort of problem in the production process that has allowed fecal bacteria to remain in this product, to get in this product, to remain in this product and then ... - Kibow_Enteric_Toxin_Removal.wmv Kibow® Biotics metabolizes nitrogenous waste that has diffused from the bloodstream into the bowel. Nitrogenous wastes are utilized by Kibow® Biotics as nutrients. As probiotics grow and multiply, they consume more nitrogenous waste and therefore effectively help maintain healthy kidney function. When these waste products accumulate in high concentrations in the blood, they become highly toxic and can cause severe damage to many organ systems if they are not properly excreted. Due to the overloaded and impaired kidneys, a buildup of poisonous wastes occurs in the bloodstream. Certain probiotic microorganisms can utilize urea, uric acid and creatinine and other toxins as its nutrients for growth. They then multiply, thereby creating a greater diffusion of these uremic toxins from the circulating blood across the lining of the intestinal walls into the bowel. This increased microbial growth is excreted along with the feces (which is normally 50% microbes by weight). Enteric toxin reduction technology uses probiotic organisms to transform the colon into a blood cleansing agent, which, with the aid of microbes, indirectly removes toxic wastes and helps eliminate them as fecal matter. Consequently, it is possible to maintain a healthy kidney function with the oral use of Kibow® Biotics. The patented, proprietary probiotics in Kibow® Biotics have been clinically tested and shown to be safe, effective and free of serious side effects when taken for as long as six months. - Explaining Gastroenteritis with Food Safety Attorney Bill Marler Food poisoning attorney Bill Marler of Marler Clark, The Food Safety Law Firm explains gastroenteritis and its role in foodborne illness litigation. Gastroenteritis is the medical term for what we've come to know as food poisoning or foodborne illness. In essence, it's the vomiting, it's the diarrhea, it is sort of a catchall phrase before the stool cultures come back, or if the stool culture comes back negative and you're still having those symptoms it's so much easier for a doctor to say, "Oh that person has Gastroenteritis, it's inflammation of the stomach lining, inflammation of your bowels." It is what is most typically understood as the definite sign of a foodborne illness. Gastroenteritis is usually the first step, and for most people it's the only step, in a foodborne illness. The vast majority of people don't get sicker. They're very ill, they may be sick for five or six days, they could have E. coli or Salmonella, Campylobacter, Shigella, all of those bacteria have similar symptoms that a doctor could lump into Gastroenteritis. However as the new CDC statistics show, about 128000 people will go on to need hospitalization, and it may be for a Salmonella illness that has gone septic or E. coli illness that has developed into Hemolytic Uremic Syndrome which may require much more intervention and dialysis and then unfortunately, Gastroenteritis will lead to the deaths of some 3000 American every year. - Child with E coli HUS: Attorney Discusses Legal Rights Attorney Elliot Olsen discusses the legal rights of a child with E. coli HUS, hemolytic uremic syndrome, a severe illness that can cause kidney failure (renal failure), brain damage, stroke, blindness, heart failure, pancreatitis, hypertension and death. Elliot and the other E. coli attorneys at Pritzker Olsen law firm represent children and adults sickened by E. coli O157:H7 throughout the United States. They also represent families in wrongful death lawsuits. To contact Elliot for a free consultation, call 1-888-377-8900 (toll free). - Veronica Lake - Love Is Blue A tribute to the beautiful Veronica Lake - The peek a boo girl. She was the actress who personified the word femme fatale. During the 1940's Veronica was one of the most popular and sought-after actresses. The clips in this video are from the movies; The Blue Dahlia This Gun For Hire The Glass Key So Proudly We Hail! Sullivan's Travels Veronica Lake is one of the biggest,brightest,most beautiful stars in Hollywood history, but sadly one of the most tragic too. She was born Constance Frances Marie Ockleman on November 14,1922 in New York. During the 1940's she made her greatest movies (four with Alan Ladd) The public loved her. She quickly became one of the most popular stars, and pretty much all women of the world tried to copy her iconic hairstyle. Ronnie was a fantastic actress-she did it all- drama, film noir, comedy, and she starred in some of the greatest classics of all time. But in the 1950's her career collapsed, the reason why she didnt get any good roles anymore, and why Paramount didn't re-new her contract, was because nobody wanted to work with her- she was suffering from alcoholism and mental illness, and that made her extremely difficult to work with. In the 1960's she was at one point working as a barmaid at a hotel in Manhattan. (when former lover Marlon Brando found out about that, he sent her a check for a thousand dollars, but out of pride she never cashed it, but kept it framed in her living room.) Veronica published her autobiography in 1972, with ... - Enlarged Prostate -- Benign Prostate Hypertrophy Natural Remedies Part 1 One of the hot spots in the body. It is reddish brown, size of an English walnut. It can disturb one's sleep by requiring several trips to the bathroom each night or kill a man by producing uremic poisoning. In old age it can become a site for cancer too. The prostate is a gland which contributes greatly to one's *ual life. It is a principal storage depot for the seminal fluid, without which chances of pregnancy will be about zero. At each ejaculation, testicles provide over 150-200 million sperms cells. The prostate produces a fluid that dilutes them and this fluid contains proteins, enzymes, fats and sugars to nourish the fragile sperm, alkalinity to overcome the deadly acidity of the female tract and a watery medium in which the sperm can swim towards female egg. It is very astonishing fact to know that the condition BPH has been explained in Ayurvedic texts long back. The anatomical positon of the prostate gland, symptoms of BPH and its remedies are explained in Acharya Sushruta.The anatomical position of prostate gland is described in Ayurvedic classics as follows. In Yogaratnakara it has been described as -- "Naabheradhasthaatsanjaatha Sanchaari Yadi Vaachalaha Ashteelaavad Ghano Granthiroodhwar Maayata Unnataha" Which means "Below umbilicus (NAABHI), there is a hard gland which is little bit bulged and changes its place some times and some times stays stationary. This ... - Susan P Fisher Hoch: WITI Hall of Fame 2008 Induction Video - Women In Technology International Susan P. Fisher-Hoch MD, Professor of Epidemiology, The University of Texas School of Public Health Sue Fisher-Hoch was born in England in 1940. After completing High School she attended the Sorbonne in Paris, then continued linguistic and cultural studies in Rome. She gained admission to the Royal Free Hospital School of Medicine in 1970 at a time when women, particularly married women as she was, were not offered places. At the Royal Free she was awarded the Elizabeth Garrett Anderson fellowship, in memory of the first English woman doctor. She graduated First Class in 1975 with seven prizes for excellence. After internship with Dr. Sheila Sherlock at the Royal Free Hospital, she joined the Radcliffe Hospital, Oxford to train in virology. Between 1978 and 1982 she taught medical students, ran virology laboratories and conducted research, publishing several papers. By 1981 she had membership of the Royal College of Pathology in Virology, a Master's degree in Microbiology with distinction and a doctoral degree in epidemiology (MD) from London University. Her doctoral thesis findings were published in the Lancet and were the first identification of hot water systems as the source of outbreaks of Legionnaire's disease, as opposed to air conditioning. She was also central to the discovery that the parvovirus B19 was responsible for Fifth's Disease (Slapped Cheek Syndrome), and in the first identification of E.coli O157 as the cause of hemolytic uremic syndrome. In 1982 she ... - Aiden's Cross 2 year old Aiden Cross has an "ultra rare" disorder called Atypical Hemolytic Uremic Syndrome. The disease attacks Aiden's own little body when his immune system is stimulated. To date, Aiden has had 9 surgical procedures, the most recent being a bilateral kidney removal just 2 weeks ago. He relies on medications and daily dialysis (for 12 hours) to survive. You cannot get this little man down...he remains upbeat and a joy to be around. AHUS affects approximately 300 families in the US. There is little research and no cure. Please spread awareness by wearing Aiden's Cross! Please visit Aiden's site @ and the site for The Foundation for Children with Atypical HUS @ for more info. Thanks for watching! - E. coli and Hemolytic Uremic Syndrome (HUS) Attorney Fred Pritzker ( ) discusses hemolytic uremic syndrome (HUS) ( ), a severe illness caused by E. coli, usually E. coli O157:H7 ( ). Shiga toxins produced by the E. coli can affect the red blood cells, causing them to be misshapen. When this happens, those misshapen blood cells can get clogged in the glomeruli, tiny vessels in the kidneys. This can block the filtration system in the kidneys that allows waste products to be removed from the body. This can lead to kidney failure and a host of other life threatening complications, including stroke, heart attack and hypertension. To contact food safety attorney Fred Pritzker for a free consultation about a personal injury or wrongful death lawsuit, please call 1-888-377-8900 (toll free). - Stroke? Call 1-800-Vampire It's unfortionate that evolution takes so long, but then again survival of the fittest. Leviticus 17:11 "For the life of the flesh is in the blood...." A stroke -- sometimes called a brain attack -- happens when a blood clot prevents blood circulation in the brain. Unless the clot is quickly dissolved, the brain cells will die. There is currently only one approved drug to dissolve these clots, but it must be given within three hours of the stroke. Unfortunately, most stroke victims don't get to the hospital that quickly. A new drug called desmoteplase has now proven safe and effective when given up to nine hours after a stroke. This is a preliminary conclusion after limited human testing. Most amazingly, this drug is made from the saliva of vampire bats! These bats must feed on blood. Typically, they pierce the skin of a cow or some other mammal. The bat saliva contains the working chemical in desmoteplase and keeps the blood from coagulating while the bat is feeding; when it is finished, the blood clots in its host quite naturally. Not only is the critical time in which desmoteplase can be applied much greater than that of the man-made drug, but it appears to carry no risk of causing a hemorrhage. Again, man has gone to one of God's designs and found something that is better than anything man could devise. That this happens every day should send the message to everyone that we are the result of a wise Creator. Prayer: Thank You, Father, for all the gifts you have given ... - 2011 New Pioneers Awards - Dr. Mohamed Karmali (Science Award) Originally from Kenya, Dr. Mohamed Karmali arrived in Toronto in 1976, after completing his medical degree in Scotland and specializing in internal medicine and infectious diseases at the University of Glasgow Teaching Hospitals. Adjusting to life in Canada and to the Canadian medical system was a challenge. However, with determination, dedication, focus and his sights set high, he overcame many of the common obstacles faced by foreign medical professionals. His hard work paid off. In 1980 he became a Fellow of the Royal College of Physicians (FRCP) of Canada with Specialty Certification in Medical Microbiology. Immediately after obtaining his FRCP qualifications, Dr. Karmali joined the Hospital for Sick Children, Toronto as Staff Microbiologist. In 1989, he became the Head of the Microbiology Department; in this position, he applied his skills in persuasion, leadership and planning to develop a department that became highly respected internationally in pediatric medical microbiology. An internationally recognized physician-scientist, Dr. Karmali has made pioneering contributions in medical microbiology and infectious diseases. His first influential work was the discovery that a major cause for childhood enteritis, a common intestinal infection, was Campylobacter jejuni. He published the first study of the natural history of this infection and pioneered the diagnostic technique, conducted epidemiological studies and investigated its antimicrobial resistance. In fact, the ... - Meet Aly: Hemolytic Uremic Syndrome For most kids, after-prom means staying up all night bowling, dancing, watching movies or just hanging out. For 16-year-old Aly Reynolds, after-prom became an extended stay at Akron Children's Hospital, much of it spent in the Pediatric Intensive Care Unit, as a mysterious case of hemolytic uremic syndrome shut down her kidneys and led to more than a few scary moments. In this Children's Channel video podcast, Aly and her mom, Andrea Joliet, share the story behind her hospital stay, highlighting the ups and downs they experienced, as well as the team that helped save her life. - Dr KP Buteyko Swimming in Snow - Cold Shower Benefits Taking cold shower and cold adaptation have always been important parts of the Buteyko breathing technique. Medical research suggested numerous benefits of regular cold adaptation and cold shower use: - increase the blood level of beta-endorphin and noradrenaline and increase synaptic release of noradrenaline in the brain as well (Shevchuk, 2008) - activation the sympathetic nervous system (Shevchuk, 2008) - electrical stimulation of peripheral nerve endings to the brain, which could result in an anti-depressive effect (Shevchuk, 2008) - reduction in muscle soreness after running a marathon (Liang et al, 2001) - significant gesic effect without noticeable side effects or cause dependence (Shevchuk, 2008) - improved quality of sleep (Onen et al, 1994) - inhibition of purine metabolism (Brenke et al, 1994) - long-term antioxidative adaptation (Brenke et al, 1994) - improved tone of the skin and muscles (Mergeay et al, 1990) - decrease of uric acid level in blood plasma (Brenke et al, 1994) - reduction in uremic pruritus (a major problem for patients with end-stage renal disease) (Zucker et al, 2003) - increase in brown fat cells or brown adipose tissue that protects from aging, fight obesity, diabetes, heart disease, etc. (Kanzleiter et al,2005; Mattson, 2010). Additional and the main factors relate to improvements in breathing parameters: slower and lighter breathing and higher body oxygen content. For references and Cold Shower Benefits, Rules and RESTRICTIONS, visit ... - Thrombotic Thrombocytopenic Purpura...Yesterday, Today and Tomorrow Thrombotic Thrombocytopenic Purpura...Yesterday, Today and Tomorrow This ppt powerpoint presentation is uploaded by: Medical powerpoint search engine. - Disgorge-The Vile Sores In Urticariothrocisism Goulashed Decrepitance Artist:Disgorge Album:Chronic Corpora Infest Year:1998 Lyrics: Grotesquely pathologyc reabsorbed Artrosis by craps ventriculloyds Exfoliative erosive ganglium The turfs makes lupose Exantematic tifea Mist in furst acra Diseminosuture in my croup lunch The juices sacarates in arormalism My saliva exagerates one lordosism And makes the tummefaccied complicates Vilism And flicteaned sorigness Chomping on your safenectomy Decrepitate in engendrance adherent Somation by exterior endo spams Sub cutaneon rectalism goulashing Spiro chaeta morsus incarnis soma Saturates my sacrophagy sodomy On your sores my vulgar taste grows Fragments on varicose oblation Internous lidistrophia in crhonicism Uremic dolours on meningo cephallia Evolutive decrepitance incongenity Aperture insides malformed glaucoma In procedence of tracto aqueous Facial precognized neuralgy Ecto acridic nauseo transform Convulsive digesting Blists embrionary localized Oncogerms fenotype on stygma Clonal in general ventriculate Rabdosarcoma feast on fungoids Seccioning and transfixioning the carcasse Malformed of neonal emancipate Infeccionous acrid lessions Cavities now on genito urinary trastorn Fractured neoprovertebrous sericid Femoro cuteanized in cronaxium Vulgarism phido spasmic pleurasy Engorging flemonose disrupt Complex of incercioned enzimopathy Cavernose collesteatomized Exfoliative teratome in plasmose cava Micose ifostamidedenigrate In your coryo the flebitys engendred Tract dolours on your nephria ... - Tell Me a Story: Dad Gives Son a Precious Gift--a Kidney Preston Henson was a toddler when his parents realized his illness on a family vacation was more than a run-of-the-mill virus. It was E. coli food poisoning that quickly worsened into a disease that began destroying his kidneys. Doctors diagnosed Preston with hemolytic uremic syndrome — known as HUS. Without a kidney transplant, doctors said Preston would need to undergo dialysis for a lifetime. His dad, Gerald, made the decision to donate one of his kidneys, and the transplant was successful. Preston is now a healthy 4-year-old who takes two medications a day and is as active as any preschooler. In this "Tell Me a Story," listen to the Hensons talk about how the decision changed their lives. - Hemolytic Uremic Syndrome (HUS) Ludovivo Guarini MD Pediatric Hematology/ Oncology Residency: Beth Israel Medical Center New York Fellowship: College of Physician and Surgeons Columbia University Produced by - Concurrent CRRT and plasmapheresis This is a video that demonstrates the technique of concurrent continuous renal replacement therapy and therapeutic plasma exchange (CCRRT+TPE). CCRRT+TPE may be useful in the treatment of children with fulminant hepatic failure, hemolytic uremic syndrome or patients with immune-mediated acute renal failure. The video was filmed by Kim Yaeger,BSN in the Center for Advanced Pediatric Education (CAPE) at Stanford University. The video was presented by Dr Peter Yorgin at the 2006 CRRT Conference in San Diego. - frequent flyer 2 music-pal shazar/vid/sherry/ The Platinum Blonde The Blonde Bombshell : Jean Harlow died from uremic poisoning from renal failure and died of cerebral edema at age 26. the cost of using caustic carcinogenic chemicals via her hair coloring dyes for platinum and the indelible inks for drawn on high-brows are absorb daily into her pores. amazing how much she accomplished in her brief 26 years of life and also only 5'1" bless her heart. and bless pal shazar's heart for this song. - ImPACKD on Rogers Ottawa with Marie-Eve Chainey Marie-Eve Chainey is a third year nursing student at the university of Ottawa. Marie-Eve works as a fitness trainer and is a competitive high jumper. She spent her time volunteering for numerous organizations and has been on dialysis since she was 18. In the fall of 2001, Marie-Eve left her hometown of Kapuskasing, Ontario to attend an exchange program in Spain; to learn a new language and continue her high jump training. After four months abroad, Marie-Eve experienced a chain of severe headaches, dwindling energy and noticeable weight gain. After a series of tests, doctors concluded that Marie-Eve had dual kidney failure due to a rare blood disorder called Atypical Hemolytic Uremic Syndrome (AHUS). Although Marie-Eve is very lucky to have access to nocturnal hemodialysis at home, she still finds travelling very difficult and after five operations fears that her fistula will stop working. Like many CKD patients, independence is what Marie-Eve works towards everyday. "There are many issues surrounding kidney disease that are not being addressed and with the formation of ImPACKD we will to finally give a voice to the CKD community." - E. coli Lawsuit Attorney for Complications of E coli and HUS E. coli lawsuit information is provided by Brendan Flaherty, an attorney with PritzkerOlsen, PA ( ), a national food safety law firm. Mr. Flaherty works with Attorney Fred Pritzker ( http ), who speaks nationally at attorney seminars, food safety conferences and law schools about food litigation and building a winning case for a food poisoning victim. Mr. Flaherty and Mr. Pritzker represent E. coli victims throughout the United States, including those who have developed life threatening complications of E. coli: 1. hemolytic uremic syndrome (HUS) - 2. thrombotic thrombocytopenic purpura (TTP) - To contact attorneys Brendan Flaherty and Fred Pritzker about an E. coli lawsuit involving personal injury or wrongful death, call 1-888-377-8900 (toll free). - Jean Harlow -Falling Star(ronstadt)Happy 100th Birthday Harlow Centennial March 3 Beautiful Linda Ronstadt song Fallen Star tagged to pics of the ever beautiful ever young Jean Harlow,always in our hearts.March 3 marks the 100th year anniversery of the birth of the forever beloved Superstar,born March 3, 1911, as Harlean Carpentier in Kansas City. Originally wealthy, Harlean nicknamed the baby was doted on by her mother, Mama Jean. At 16, Harlean married the well off Charles MacGraw, but marriage ended when Mama Jean decided to move with the baby to Los Angeles, after the Senior Jean had failed at stardom. Harlean landed roles in a Laurel and Hardy and in the woman whom she would replace as Americas Goddess the gorgeous Clara Bow in The Saturday Night Kid. The elder star liked the youngster,seen unflatteringly in her bit role. After several extra background roles, Harlow was discovered when multimillionaire Howard Huges decided to make his then most expensive film ever, "Hell's Angels"into a talkie and German actress Greata Nissens voice was unsuitable for the role. Harlow's carefree uality actuality,gorgeous face and magnificent body made her the most famous woman in America. Five films in 1931 followed , all hits, including The Public Enemy with James Cagney,but the public felt Harlow couldnt act. Hughes sold her contract to MGM, and she made a promising first appearance with a total done over heavily made up look in the B, Beast of the City. Harlow's sensational teaming with Clark Gable in "Red Dust" made her a superstar, and she stole the ... - Hemolytic Uremic Syndrome (HUS): Tracking an Epidemic of E-coli Poisoning View this Lecture for FREE by signing up at Viewany number of our other 28000 sessions from over 280 conferences by going to Speaker(s) Nancy McAfee, MN, RN, CNN Hemolytic Uremic Syndrome (HUS): Tracking an Epidemic of E-coli Poisoning - American Nephrology Nurses Association National Symposium 2008 Nephrology Nursing and Evidence-Based Practice: In Harmony to Improve Patient OutcomesRemember, if you attended this meeting you have Free Access to this content! Click here for more information.All invited faculty members and planning committee members participating in an ANNA-sponsored program are required to disclose any real or apparent conflict(s) of interest that may have a direct bearing on the subject matter of the educational activity. To review speaker disclosures, click hereThe presence of any product, company, or corporation in any recording or content in no way signifies an endorsement of the product, company or corporation by ANCC Commission on Accreditation or the American Nephrology Nurses' Association (ANNA).Contact Hours available through: 6/1/2010Please note: Learners may earn contact hours (for recertification or relicensure) for each educational activity once only. If you attended a session at a live meeting (National Symposium, Fall Meeting, Audio Conference, etc.), you cannot repeat and claim credit for that session again. While the session is now offered online in a different format, the educational content is ... - Faith Healing Death - Oregon City Followers of Christ Church The death of a 16-year-old Oregon boy being treated by a faith healer could have easily been prevented according to a state medical examiner. The 16-year-old member of a faith healing church died of uremic heart failure caused by a stricture in his urinary tract, according to autopsy results. The condition could have been treated with a catheter in a routine outpatient procedure. Instead, 16-year-old Neal Beagley's urinary tract became inflamed and closed off. He was unable to urinate, which made his bladder and kidneys stop functioning, the autopsy showed. Toxins backed up into his blood stream. Beagley had started complaining about stomach aches and shortness of breath last week. The family told police he did not want medical attention. Gladstone police said relatives and church members told them the **ager refused treatment for the illness, as he was entitled to do under Oregon law. The family belongs to the Oregon City Followers of Christ Church. Like all members of the religious order, Beagley did not receive medical care. His condition worsened Sunday and members of the church gathered for prayer, Benton said. The church is a fundamentalist Christian denomination that recently made headlines after two members were arrested and accused of using prayer instead of medical care to try to cure their deathly ill daughter. In March, the boy's 15-month-old cousin, Ava Worthington, died at home from bronchial pneumonia and a blood infection. Her parents, Carl and Raylene ... - Have a Blythe Xmas! Blythe, everyone's favorite doll from the 70's with uremic leontiasis osse, helps Japanese department store Parco celebrate Christmas. Styled by the fabulous Gina Garan. Blogs & Forum blogs and forums about uremic “Hemolytic Uremic Syndrome Outbreak: Lawyer and lawsuit information. Pritzker Olsen Law Firm Food Safety Blog. Pritzker Olsen attorneys have appeared on CBS News, Fox news, and numerous local television stations throughout the country” — Hemolytic Uremic Syndrome Outbreak, “Uremic Frost. The Nephrology Blog. Tuesday, October 13, 2009. Kidney Public Policy Forum. The Renal Support Network has sponsored a forum dedicated to the CMS Proposed Rule for CKD / dialysis. Comments are due by November 16th. Please log on and contribute prior to this landmark ruling” — Uremic Frost: Kidney Public Policy Forum, “"It's just hard to put into words," says the grandmother, Sue Henderson, of a Corning, California girl sickened by E. coli O157:H7. "Yo Add this blog to your feeds or subscribe by email More Request Info. See our list of services or enter your information below to send us a quick message and we'll” — Northern California girl recovering from hemolytic uremic, “Hemolytic uremic syndrome is a condition in which the red blood cells disintegrate and lead to problems in the normal functioning of the kidneys and renal failure. Mostly affects children below the age of 10 years” — Hemolytic Uremic Syndrome in Children \| Symptoms \| Treatment, home-remedies-for- “Hemolytic Uremic Syndrome (HUS) induced kidney injury by Shiga-Toxin E. coli - Guest Blog - Bruce T. Clark, JD Uremic Syndrome (HUS) induced kidney injury by Shiga-Toxin E. coli - Guest Blog - Bruce” — Hemolytic Uremic Syndrome (HUS) induced kidney injury by, “hemolytic uremic syndrome. Post Reply. Author. 2 Posts. asmi. Forum Hero. Topics: 1049. Posts: 4, Similar forum topics. hemolytic uremic syndrome. Hemolytic jaundice” — hemolytic uremic syndrome, prep4 “Welcome to the Elaine Moore Graves' and Autoimmune Disease Education site for the support and education of patients with Graves' Disease and other autoimmune disorders. Here you'll learn about the autoimmune nature, symptoms, diagnosis and” — Elaine Moore Graves' and Autoimmune Disease Education > My, elaine- “Healthchannels forum, An online health community from , Inc. Discuss Hemolytic Uremic Syndrome with others. 6 Topics. Last post by TessaP. on Thu Aug 07, 2008 7:41 pm. Published Stories - Read Entries. Read published stories submitted by other browsers. 2 Topics. Last post” — Hemolytic Uremic Syndrome: - Nephrology Channel, related keywords for uremic - uremic poisoning - uremic frost - uremic syndrome - uremic encephalopathy - uremic pericarditis - uremic bleeding - uremic fetor - uremic breath - uremic pruritus - uremic toxins - uremic poisoning brought on by acute nephritis - uremic poisoning pregnancy - uremic poisoning acute nephritis - uremic poisoning in dogs - uremic poisoning cats - uremic poisoning jean harlow - uremic poisoning symptoms - uremic poisoning causes - uremic poisoning in cats - uremic poisoning death	2	18	2	0	0	1	0.703616	3	8,926
What is Autism? Autism spectrum disorder (ASD) is a pervasive developmental disorder characterised by a triad of symptoms; impaired social skills, rigid communication style & characteristic repetitive and ritualised behaviours. Although, it is considered a lifelong condition, one’s impairments can significantly improve with appropriate awareness, support and, where required, intervention. ASD could be considered an umbrella term for autistic conditions as seen in the ICD and DSM diagnostic manuals. ICD-10 outlines eight conditions under F84: childhood autism, atypical autism, Rett’s syndrome, other childhood disintegrative disorder, overactive disorder associated with mental retardation and stereotyped movements, Asperger’s syndrome, other pervasive developmental disorders and pervasive developmental disorder, unspecified. DSM-IV set out five conditions within chapter one’s description of pervasive developmental disorders: autistic disorder, Rett’s disorder, childhood disintegrative disorder, Asperger’s syndrome and pervasive developmental disorder - not otherwise specified, including atypical autism. The most recent version of the DSM diagnostic criteria, DSM-5 combined autism, Asperger’s syndrome and pervasive developmental disorder into a single diagnosis and changed the name of this group from ‘pervasive developmental disorders’ to ‘autism spectrum disorder’ (American Psychiatric Association, 2013). Although the category remains broad, DSM-5 no longer provides differing criteria for each condition, instead a single set of criteria can be used to diagnose ASD. The ICD-10 and DSM-5 criteria: Diagnostic Criteria for Subtypes of Autism Spectrum Disorder International Classification of Diseases-10 (World Health Organisation, 1992) ‘A. Abnormal or impaired development is evident before the age of 3 years in at least one of the following areas: 1. receptive or expressive language as used in social communication. 2. the development of selective social attachment or of reciprocal social interaction. 3. functional or symbolic play. B. A total of at least six symptoms from (1), (2) and (3) must be present, with at least two from (1) and at least one from each of (2) and (3) 1. Qualitative Impairment in social Interaction are manifest in at least two of the following areas: a) failure adequately to use eye-to-eye gaze, facial expression, body posture and gestures to regulate social interaction. b) failure to develop (in a manner appropriate for mental age, and despite ample opportunities) peer relationship that involve a mutual sharing of interests, activities and emotions. c) lack of socio-emotional reciprocity as shown by an impairment or deviant response to other people's emotions; or lack of modulation of behaviour according to social context; or a weak integration of social, emotional and communicative behaviours. d) lack of spontaneous seeking to share enjoyment, interests or achievements with other people (e.g. a lack of showing, bringing or pointing out to other people objects of interest to the individual). 2. Qualitative abnormalities in communication as manifest in at least one of the following areas: a) delay in or total lack of development of spoken language that is not accompanied by an attempt to compensate through the use of gestures or mime as an alternative mode of communication (often preceded by a lack of communicative babbling). b) relative failure to initiate or sustain conversational Interchange (at whatever level of language skill is present) in which there is reciprocal responsiveness to the communications of the other person. c) stereotyped and repetitive use of language or idiosyncratic use of words or phrases. d) lack of varied spontaneous make-believe play or (when young) social imitative play. 3. Restricted, repetitive and stereotypes patterns of behaviour, interests and activities are manifested in at least one of the following: a) an encompassing preoccupation with one or more stereotyped and restricted patterns of interest that are abnormal in content of focus, or one or more interests that are abnormal in their intensity and circumscribed nature though not in their content or focus. b) apparently compulsive adherence to specific non-functional routines and rituals stereotyped and repetitive motor mannerisms that involve either hand or finger flapping or twisting or complex whole body movements. d) preoccupations with part-objects of non-functional elements of play materials (such as their order, the feel of their surface or the noise or vibration they generate). The clinical picture is not attributable to the other varieties of pervasive developmental disorders, specific development disorder of receptive language with secondary socio-emotional problems, reactive attachment disorder or disinhibited attachment disorder, mental retardation with some associated emotional or behavioural disorders, schizophrenia of unusually early onset and Rett’s syndrome’. A. Abnormal or impaired development is evident at or after the age of 3 years. B. There is insufficient demonstrable abnormalities in one or two of the three areas of psychopathology required for the diagnosis of childhood autism (namely reciprocal social interactions, communication or restrictive, stereotyped, repetitive behaviours). C. Atypical autism constitutes a meaningfully separate condition from childhood autism. A. Diagnostic criteria 1 - 3 of B are fulfilled for childhood autism. B. No evidence of general delay or retardation in language or cognitive development. C. Generally associated with normal intelligence. Diagnostic and Statistical Manual of Mental Disorders-5 (American Psychiatric Association, 2013) Autism spectrum disorder (ASD) A. Persistent deficits in social communication and social interaction across multiple contexts, as manifested by the following, currently or by history: · Deficits in socio-emotional reciprocity. · Deficits in non-verbal communicative behaviours used for social interaction. · Deficits in developing, maintaining and understanding relationships. B. Restricted, repetitive patterns of behaviour, interests, or activities, as manifested by at least two of the following, currently or by history: · Stereotyped or repetitive motor mannerisms, use of objects or speech. · Insistence on sameness, inflexible adherence to routines or ritualised patterns of verbal or non-verbal behaviour. · Highly restricted, fixated interests that are abnormal in intensity or focus. · Hyper- or hypo- reactivity to sensory input or unusual interest in sensory aspects of the environment. C. Symptoms must be present in early developmental period. D. Symptoms cause clinically significant impairment in social, occupational or other important areas of current functioning. E. These disturbances are not better explained by intellectual or global developmental delay. Autism and Physical Illness Erroneously early researchers thought that individuals with autism spectrum disorder did not perceive pain and did not communicate their distress; perhaps lacking the ‘social inclination’ to do so (Lainhart 1999). In the mid 2000’s, researchers hypothesised that those with ASD actually have difficulty reporting physical ailments and instead express pain and physical distress as agitation and / or behavioural disturbance (Russell 2005). Although current literature on physical illness in adults with ASD is sparse, a 2016 study by O’Rourke revealed a prevalence rate of 84% for at least one physical health condition among adults with ASD. Atopy was the most commonly diagnosed condition and epilepsy was also notably more common in those with ASD. Although historically considered almost diagnostic for ASD, eating disturbance is now known to occur in approximately 25% of adults with ASD. Restricted dietary repertoire was most commonly reported, followed by reduced appetite, picky eating, eating only a single meal per day, only eating when alone, unhealthy dietary choices, binge-eating and overeating (O’Rourke 2016). Available research in relation to gastrointestinal disease in ASD is varied and controversial. However, available literature would suggest that previously reported higher rates of gastrointestinal disease in individuals with ASDs were greatly exaggerated. Sleep is a relatively well-researched topic in ASD. In fact, it has been referred to as the second most researched area of ASD comorbidity, only surpassed by epilepsy (Mannion 2014). Sleep studies in normal IQ infants with ASD have shown that 90% of sleep difficulties start at an early age including difficulty falling asleep, more frequent night waking and early morning waking (Øyane 2005). Studies of school-age children with ASD have noted difficulties with bedtime resistance, increased sleep latency, poor sleep maintenance, early morning waking, reduced sleep time and quality, increased night waking and irregular sleep patterns in 50% - 80% of subjects (Øyane 2005, Limoges 2005, Canitano 2007, Reynolds 2011). Insomnia rates of 36% have been reported in the child population, most commonly middle insomnia, followed by initial insomnia (Mattila 2010). Adolescent and young adult studies also identify a high prevalence of sleep disorders (80%) including low sleep efficiency, short total sleep time, long sleep latency, more frequent shifts into REM sleep from waking and increased REM sleep disruption (Ghaziuddin 2002a, Øyane 2005). In general, it is acknowledged that motor skill deficits are frequently observed in patients with ASD with a prevalence of 21% - 100% (Gowen 2012). Asperger described awkwardness as typical in autistic psychopathy (Wing 2002a, Barnhill 2007, Raja 2009) while Kanner (1943) noted that several children under his care were somewhat clumsy in gait with gross motor deficits but all were skilled in fine motor movements. Although not included in the DSM-5 diagnostic criteria, clumsiness is commented upon in the ICD-10’s description of Asperger’s syndrome (World Health Organisation 1992). Wing (1981) observed poorly co-ordinated movements, odd posture and abnormal gait while more recently Vannucchi (2014) described clumsiness and illegible handwriting as atypical features of Asperger’s syndrome and Van Wijngaarden-Cremers (2014) noted clumsiness in the case of a 14 year old girl with Asperger’s syndrome and comorbid drug addiction. Autism and Mental Illness Increasingly autism spectrum disorder is associated with a higher prevalence of mental illness than seen in the general population (Stewart 2006, Nylander 2008, Raja 2008). Roy (2015) noted a lifetime prevalence of one or more comorbid psychiatric illness in 70% of adults with High-functioning ASD. Rates of anxiety spectrum disorders are higher in the ASD population compared to the general population, including obsessive compulsive disorder, generalised anxiety disorder, social phobia and agoraphobia (O’Rourke 2016). Rates for mood disorders range from 24% - 53% (Ketelaars 2008, Hofvander 2009, Stunz 2014). Lifetime prevalence of major depressive disorder is 70% - 77%, recurrent depression 50%, current depressive episode 30% and dysthymia 8% (Cath 2008, Lugnegård 2011, Joshi 2013). O’Rourke (2016) identified a prevalence rate of 25% for deliberate self-harm and a rate of 16% for self-injurious behaviour in autistic adults. Schizoid, schizotypal, paranoid, obsessive-compulsive, anxious-avoidant and dependent personality styles are more common in autistic adults than in the general population (Anckarsäter 2006). Schizophrenia has a lifetime prevalence of 0.30% - 0.87% in the general population (Perälä 2007, Van Os 2009). Rates among those with ASD are less clearly defined. As early as the 1940’s, Asperger noted that only one of the 200 cases he studied developed schizophrenia (Wing 1981). Volkmar and Cohen (1991) restarted the debate on comorbidity between ASD and schizophrenia when they identified only a single patient with schizophrenia from 163 cases assessed. Volkmar and Cohen (1991) described schizophrenia as rare in those with ASD, ‘no more commonly observed together than would be expected by chance’. While research on eating disorder in autistic adults is scarce, it is agreed that ASD is over-represented in the anorexia nervosa population (Oldershaw 2011). A single study was identified which showed a prevalence rate of 5% for comorbid ASD and eating disorder. The comparable occurrence rate in the general population is anorexia nervosa 0.9% and bulimia nervosa 1.5% for women and anorexia nervosa 0.3% and bulimia nervosa 0.5% for men (Hudson 2007).s New Autism Assessment Why Assess for Autism? Wellbeing, ‘the state of being happy, healthy or prosperous is recognised as lower for those with ASD compared to neurotypical counterparts particularly in relation to physical, psychological, social supports and peers (Biggs 2016, Merriman-Webster 2018). Poorer wellbeing is particularly evident at times of transition, including the transition to adulthood, when significant attention needs to be focused on ensuring adequate services, supports and relationships to facilitate a successful outcome (Biggs 2016). Wellbeing and similarly quality of life is difficult to accurately quantify but factors which are known to impact on outcome in those with ASD include ‘physical wellbeing, material wellbeing, interpersonal relationships, social inclusion, personal development, self-determination, emotional wellbeing and rights’ (Plimley 2007, p.207). It is essential that supports and services which can optimise wellbeing and quality of life are provided early in a child’s life and for those who receive a late diagnosis as soon as possible after diagnosis. Needs change as a person ages, the needs of a child differ to those of a teenage, an adult and an older adult. Needs also change at times of transition such as moving from Montessori to national school to secondary school to University or work, when a relationship ends or a person is bereaved or when an individual struggles as peers or siblings move to another life stage such as relationships, marriage or having children while they themselves may not. The majority of autistic adults are single & living with their parents, up to 91% are unemployed, up to 95% have been bullied and up to 40% have been sexually or financially exploited (O’Rourke 2016). Knapp, Romeo and Beecham (2009) showed the estimated lifetime cost for an adult with ASD to range from £800,000 to £1,230,000. To address these barriers to positive outcomes, supports and services should be person-centred, unified across medical and social care models, available when needed and available on an ongoing basis from infancy to old age (Plimley 2007). Evidence-Based Assessment According to International Best-Practice Guidelines Autism spectrum disorder can be behaviourally defined by diagnostic criteria specifying pervasive qualitative differences in social and communication skills and behaviour. However, as yet, there are no definitive medical tests, biochemical, neuroimaging or otherwise to detect autism spectrum disorder. Hence, diagnosis relies heavily on detailed history and observation of behaviour by skilled clinicians using the ICD-10 and / or DSM-5 criteria. International Assessment Guidelines: NICE and Sign recommend diagnosis by a minimum of two clinical disciplines trained in assessment and diagnosis of ASD. An ASD assessment can include: 1. Screening - IQ appropriate tools for patient and carer. 2. Clinical History - based on ICD or DSM Diagnostic criteria. 3. Observational assessment - clinical and ADOS-2. 4. History of functioining outside the clinical setting. 5. Developmental History: both clinical history and ADI-R. 6. Individual profiling e.g.IQ, communication skills, adaptive skills, sensory profile where relevant. 7. Investigations e.g. Genetic testing, audiology, eyetest, MRI Brain, EEG where relevant. 8. Assessment for comorbid physical and/or psychiatric illness. Note: A recent systematic review by Wigham et al (Autism 2018; Feb 1:1-19) advises caution when using screening questionnaires with patients with a comorbid mental illness; interpretation is less reliable as screening tools are less sensitive and specialist discrimination between autism and a mental illness is required. The Autism Assessment at Core Clinical At the beginning of an ASD clinical assessment, we ask you and a family member, nominated by you, to complete a number of screening questionnaires which we use to triage your information towards a more efficient assessment. This information can also assist in developing an individual profile for each person attending our service allowing for a more informative feedback session following review. Each New Autism Assessment at Core Clinical is undertaken in a multidisciplinary format in line with international best practice. Both a psychiatrist and psychologist will interview you and your nominated family member(s) to ensure the assessment is appropriately comprehensive. We use structured interview, clinical observation and evidence-based diagnostic tools to reach a diagnosis. The assessment is expected to last 3 to 4 hours with each clinician. Consensus Meeting, Feedback and Recommendations Before reaching a clinical decision in relation to a person’s diagnosis, the multidisciplinary team engage in a consensus meeting. This meeting combines information gathered over the course of the assessments to allow a multidisciplinary diagnostic formulation and the development of individualised recommendations. As a team we will meet with you and your nominated family member(s) to discuss our findings and outline our recommendations. We endeavour to complete this process on the second day of your assessment. Where this is not possible due to factors such as missing information, co-existing disorders or a requirement for further assessment (e.g. IQ assessment) we will explain the reasons why and offer you options as to how to proceed. It is our preferred practice to meet with each individual that receives a new autism diagnosis within 4-6 weeks of their assessment appointment. This follow-up session is to provide space for further discussion of the diagnosis and to address questions the individual may have. Previous Autism Diagnosis If you have previously had an autism diagnostic assessment: If you have a previous diagnosis of autism and wish to attend Core Clinical for psychotherapy with our clinical psychologist, we are happy to receive a letter or email detailing your query. For the remainder of 2019, we are no longer accepting new referrals for psychiatric consultation / treatment. This applies only to our autism service, our ADHD psychiatry service is unaffected. We are saddened by this development and hope we will be in a position to revise this in 2020. To facilitate a consultation with our psychologist, we will require a copy of your previous diagnostic report. This is in line with Irish Guidelines for practice, as per a recent HSE Review of Irish Autism Services: Report of the Review of the Irish Health Services for Individuals with Autism Spectrum Disorders, 2018. This paper states that: 'As well as assisting in the provision of a diagnosis, assessment tools should identify strengths, skills and impairments to inform post-diagnostic needs-based care plans'. To understand your autism-related needs, we require this report which will contain information from the clinicians, describing your background, autistic difficulties, match these difficulties to the diagnostic criteria (DSM IV/5 or ICD-10) and contain the results of a structured assessment tool (which research has proven can reliably detect autism, of which there are 2, the ADOS and ADI-R). Many people will have received a copy of this report at the time of diagnostic assessment. If you do not have a copy, we suggest you contact the service who completed your assessment or ask your GP if they have a copy. This report can be sent in at the same time as your referral letter (by your GP) or you can send it yourself to [email protected] and Margaret, our secretary, will ensure it is linked to your referral information. What is ADHD? Attention Deficit Hyperactivity Disorder (ADHD) is a behavioural disorder that is characterised by difficulties in concentrating, being overactive and acting without thinking. If there are only symptoms of problems with paying attention and few difficulties with hyperactivity, Attention Deficit Disorder (ADD) is diagnosed. The symptoms of ADHD are present from a young age and most people are diagnosed between 6 and 12 years of age. Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common childhood psychiatric disorders. It was traditionally thought that the disorder resolved during late adolescence or early adulthood. However, more recent studies have found that clinical symptoms and psychosocial impairments persist and by age 25 years 15% retain the full diagnosis with a further 50% in partial remission. Difficulties in recognising adult ADHD can arise due to differences in symptomatology across the life-span, presence of co-morbid mental health disorders, stigma or a lack of services. New ADHD Assessment What to Expect on the Day of Assessment The initial assessment will take approximately two hours and is conducted by a consultant psychiatrist. This assessment will include a complete review of ADHD related difficulties and symptoms, personal, psychiatric and medical history (including a personal or family history of heart disease), neurodevelopmental history and mental health evaluation. You will be asked to complete a number of screening and information questionnaires prior to the appointment and during the assessment a Conner’s Adult ADHD Diagnostic Interview for DSM (CAADID) will be completed. It would be helpful if you could bring: · Any school reports you may have · Previous assessment reports, such as from a psychiatrist, psychologist or paediatrician A collateral history is usually taken on the day of your assessment, from a parent or someone who knew you well when you were a child. It would be helpful if they can accompany you to the assessment. Sometimes the assessment process takes more than one meeting and you may meet more than one member of the adult ADHD team, such as the psychiatrist, psychologist or occupational therapist. The clinical assessment information and results of the structured assessment, alongside referral information and additional reports are collated by your psychiatrist to reach a diagnostic opinion. These findings will be discussed with you after the assessment process by your psychiatrist. During this session you will be told if you have adult ADHD or not. If you have adult ADHD you will be told about the treatment options available in the Adult ADHD Service. These options include further information about what ADHD is and straightforward things to help you manage your difficulties, as well as medication and psychological therapy options. If you do not have adult ADHD you will be advised where you can go for further help and support. This may include returning to your GP for onward referral to a local adult psychiatrist or other clinical discipline. Previous ADHD diagnosis If you have previously had an ADHD diagnostic assessment: If you have a previous diagnosis of ADHD and wish to attend Core Clinical for a consultation regarding medication, therapy or supports, we will require a copy of your previous diagnostic report. Many people will have received a copy of this report at the time of diagnostic assessment. If you do not have a copy, we suggest you contact the service who completed your assessment or ask your GP if they have a copy. This report can be sent in at the same time as your referral letter (by your GP) or you can send it yourself to [email protected] and Margaret will ensure it is linked to your referral information. Core Clinical Adult ADHD Service provides structured assessment and evidence-based multi-modal interventions to adults with suspected or previously-diagnosed ADHD. We are happy to discuss with you both pharmacological and non-pharmacological treatment options available for ADHD, the risks and benefits of each approach and to assist you in reaching a decision regarding the best option for you. Not all patients diagnosed with ADHD require follow-up or intervention services but where follow-up is appropriate and required it will be offered. After a period, many patients return to their GP and attend Core Clinical for yearly medication review in line with international best practice guidelines.	2	10	0	0	0	2	0.638647	2	4,973
ICD-10 Diagnostic Criteria ID represents a group of conditions characterized by impairment of skills manifested during the neurodevelopmental period, skills which contribute to the overall level of intelligence, i.e. cognitive, language, motor, and social abilities*. ID can occur with or without any other mental or physical condition. Intellectual abilities and social adaptation may change over time, and, however poor, may improve as a result of training and rehabilitation. Diagnosis should be based on the current levels of functioning. Degrees of ID are conventionally estimated by standardized intelligence tests. These can be supplemented by scales assessing social adaptation in a given environment. These measures provide an approximate indication of the degree of ID. The diagnosis will also depend on the overall assessment of intellectual functioning by a skilled diagnostician. If desired, additional codes are used to identify associated conditions such as autism, other developmental disorders, epilepsy, conduct disorders, or severe physical handicap. A fourth-character subdivision is used to further signify ID categories (F70-F79) in order to identify the extent of impairment (or severity): .0 With the statement of no, or minimal, impairment of behavior .1 Significant impairment of behavior requiring attention or treatment .8 Other impairments of behavior .9 Without mention of impairment of behavior Approximate IQ range of 50 to 69 (in adults, mental age from 9 to under 12 years). Likely to result in some learning difficulties in school. As adults individuals will be able to work and maintain good social relationships and contribute to society. Approximate IQ range of 35 to 49 (in adults, mental age from 6 to under 9 years). Likely to result in marked developmental delays in children but most can learn to develop some degree of independence in self-care and acquire adequate communication and academic skills. As adults they will need varying degrees of support to live and work in the community. Approximate IQ range of 20 to 34 (in adults, mental age from 3 to under 6 years). Likely to result in continuous need of support. F73 Profound Mental Retardation IQ under 20 (in adults, mental age below 3 years). Results in severe limitation in self-care, continence, communication and mobility. Individuals who have an age of onset after 18 qualify for the diagnosis qualify for F78 Other, and in those IQ range is not known, it is referred to as F79 Unspecified. Adapted with permission for International Statistical Classification of Diseases and Related Health Problems 10th Revision <http://apps.who.int/classifications/icd10/browse/2010/en> Intellectual Disability ...	4	11	0	0	0	4	0.882932	4	547
Department and Clinic of Internal Diseases, Allergology and Clinical Immunology, Medical University of Silesia in Katowice Department and Clinic of Internal Diseases, Allergology and Clinical Immunology, Medical University of Silesia in Katowice The article has been published at a special request of Journal's Editorial Board due to the importance of the subject matter. It has not undergone the review process and it has been published in Polish language in Alergologia Polska Journal. The International Statistical Classification of Diseases (ICD) is a classification system created and owned by the World Health Organization (WHO). The history of the ICD goes back over 100 years. The first version of the so-called "International List of Causes of Death" was created in the eighteenth century (1893) and concerned only the causes of death. The subsequent updates were extended to include numerous disease entities and health problems, up to the current tenth version of the ICD-10, approved in May 1990. The ICD has been translated into more than 40 languagesand is used in more than 150 countries. The International Classification of Diseases is updated regularly, averagely every 10 years. ICD-10 is widely used for the reimbursement and deployment of funds in the healthcare system. ICD-10 has been in force in Poland since 1997. The procedure coding is used to estimate the costs of performed procedures, including surgical interventions. The National Health Fund decides to grant reimbursement for a specific treatment, based on ICD codes, which are attached to invoices issued by the treatment centres. Each procedure performed on a patient during hospitalization is coded. If a patient needs more than one procedure, the treatment procedures (e.g. surgical intervention) have more beneficial coding than diagnostic procedures, and thus are better paid by the National Health Fund. The current version of the ICD is not sufficient enough for the precise verification of the procedure payments and the assignment of patients to specific therapeutic groups, therefore it needs to be extended. Based on numerous analyses, it has been shown that the ICD has become an important tool in the field of health, including monitoring disease prevalence, assessing causes of death, external causes of diseases, including drug resistance and monitoring rare diseases. Some countries, including Australia, Germany, Canada and the USA have expanded the ICD-10 by adapting it to their own needs. With time and the rapid development of individual fields of medicine, the need for detailed recording and documentation of the new clinical conditions has increased, therefore the previous version began to lose its relevance. The work on ICD-11 began in 2011, in June 2018 the World Health Organization (WHO) published on its website a new version of the International Statistical Classification of Diseases and Related Health Problems). In May 2019, the ICD-11 was approved by the 72nd World Health Assembly (WHA72). Currently, the version is being consulted with the WHO member countries and enters into common use on 1 January 2022. The main reason of creation the new ICD-11, was the need to reorganize all diseases basing on the latest medical knowledge. The study involved not only doctors but also public health professionals, statisticians, epidemiologists and representatives of institutions financing public health systems. The ICD-11 classification has been modified and adapted for clinical purposes, for statistics, monitoring morbidity and mortality and will also be a helpful tool for planning expenses in the health care system. It is worth noting, that more than 70% of global health expenditure is currently based, according to the National Centre for Health Statistics, on the ICD classification, which in 2018 accounted for $3.6 trillion . The complete digitalization of the latest version of the ICD will be an event of the 21st century. The fully electronic version will significantly facilitate the work with the IT systems in health care facilities. Differences between ICD-10 and ICD-11 In comparison to the previous version of ICD-10, ICD-11 will be more precise and transparent. The classification will still be based on alphanumeric coding, while the number of chapters, individual characters and possible codes have been significantly increased. The latest version of the ICD will contain approximately 55,000 codes, with the possibility of extending the database. In order to facilitate the coding of individual diseases and medical interventions, completely new chapters have been created. ICD-11 consists of 26 main chapters and 2 additional subsections (V and X), which include systems and individual organs, causes of diseases and deaths. There is also a chapter on traditional medicine. The latest version of the ICD has been extended by family medicine issues , antibiotic resistance, a list of drugs, allergens, chemicals, as well as results of histopathological examination. The tenth revision uses alphanumeric coding with a letter in the first place, numbers in the next three positions and the fourth character after the period. The codes start from A00.0 till Z99.9. Each nosological unit is marked alphanumerically: A12.X, where A - is a letter, 12 is a number, X - a number that identifies the subtype. The subtype 8 indicates “other” and the subtype 9 indicates “undefined”. The "U" codes are intended for the new diseases of uncertain aetiology. As for the 11 version of the ICD, the codes range from 1A00.00 to ZZ9Z.ZZ, while the codes in group "X" are extension codes, that allow a more detailed description of the course of the disease. For example, allergic asthma which in ICD-10 is under the code of J45.0, in ICD-11 is under the code of CA23.0. Extended ICD-11 database, enables us to code the allergic, severe asthma with acute episodes: CA23.00 & XS25. The basic differences between ICD-10 and ICD-11 are presented in Table 1. Number of codes 26 chapters, 2 subsections Possibility to extend the code Yes, codes from the "X" group Allergic diseases in ICD-11 Allergic diseases are considered to be the epidemic of the 21st century. It is estimated that almost one third of the world's population (25-30%) suffers from allergic diseases, including over 150 million Europeans. and the figures are rising drastically every year. Allergy and hypersensitivity are the fourth most common group of chronic diseases and one of the main problems in public health. The WHO predicts that in 2050 every second person in the world will suffer from allergy, especially in industrialized countries. Due to the multi-organ clinical manifestation of allergic diseases, specialists in many fields of medicine have contact with allergic patients. Most cases of allergies or hypersensitivity are treated by general practitioners, paediatricians, ERT (Emergency Rescue Team) and UCU (Urgent Care Unit) physicians. In the current ICD-10, allergic conditions were characterized too generally. The allergic diseases include asthma, anaphylaxis, allergic rhinitis, food and drug allergy, urticaria, angioedema, atopic dermatitis and many others. Apart from their wide clinical manifestation, the allergic diseases are characterized by various pathomechanisms, triggers and symptom severity. This affects not only the patient’s quality life, but also the costs of treatment for patient and the entire healthcare system. The diagnosis of an allergic disease is not always easy and is based mainly on a carefully collected medical history, physical examination, and in vivo and in vitro diagnostic tests. The basic in vivo tests include skin prick tests, intradermal tests - used in the diagnosis of IgE-dependent allergy, patch tests - used in the diagnosis of contact allergy, and provocation tests - the "gold standard" in the diagnosis of food, drug or inhalation allergy. Provocation tests allow to confirm the diagnosis, indicate factors causing an allergic reaction, choose a safe drug, test the new therapeutic options, and monitor the course of the disease. It is worth mentioning, that in vivo tests, such as intradermal and patch tests are used in allergology for over 100 years, due to their very high usefulness, which is emphasized by the current guidelines and recommendations of recognized Allergy Scientific Societies [5, 6] On the other hand, in vitro studies such as determination of specific IgE concentration, tryptase level, , basophil activation tests (BAT), lymphocyte transformation tests (LTT) are helpful in confirming the diagnosis and are a safe alternative to in vivo tests, especially among patients with severe allergic diseases. These tests cannot be used as screening tests and their results should always be interpreted with caution. Most of these methods still require validation to ensure appropriate sensitivity and specificity. Proper diagnostics, both in vivo and in vitro, is helpful in optimizing the treatment expenses in both health care systems (public and private). In the current model of the health care system, the costs of diagnosis and treatment of a patient are based on the coding of specific diseases. In this regard, the ICD is the most common system that tracks the incidence of diseases, the costs of their diagnosis and treatment. So far, the allergic diseases have not been accurately represented and properly coded in the ICD. This resulted in underestimation of their occurrence and errors in statistical studies on incidence and mortality as well as had a negative impact on the diagnosis and treatment of patients. In 2012, Tanno et al. presented data according to which the ICD-10 does not reliably provide the number of deaths caused by anaphylaxis, significantly underestimating this value. It soon turned out that the problem also refers to other allergic diseases and hypersensitivity reactions. In the international survey on classification and coding of allergic diseases, which was attended by 612 EAACI and/or WAO members from 144 countries, the majority of respondents considered that the ICD, despite being the most common disease classification system in the world, is not suitable for use in clinical practice. According to most of the respondents, the classifying of hypersensitivity/allergic diseases in the ICD-10 is neither easy nor accurate. The work on the new ICD qualification has become a unique opportunity to improve the classification of allergic disease coding. It was necessary to prove the need to make changes in the ICD, with respect to the allergic diseases and prepare an appropriate high-quality document for WHO ready for implementation in the new ICD-11 edition. The hardest thing in formation of the new ICD-11 classification was to create appropriate codes for diseases in connection with the diagnostic procedures necessary for the correct diagnosis. Under the leadership of Luciana Tanno and Pascal Demoly, a list of diagnostic procedures (keywords) relevant for allergic/hypersensitivity diseases and used by specialists in their daily practice was prepared. (Table 2). Table 2 Diagnostic procedures used in allergology. The authors of the study were aware of the fact, that some in vitro procedures have been used so far only for the purposes of clinical trials, in selected research centres in few countries, but the increasing number of publications on their usefulness suggested that they would be most likely used in everyday practice in the future. Selected procedures in the ICD-10 (2015 version) were compared with the ICD-11 beta version (2015). The analysis of currently applied ICD-10 and the draft ICD-11 version has drawn a picture of many shortcomings, imprecise terminology and the dispersion of allergology issues across the various chapters of the ICD. Diagnostic procedures for Diagnostic procedures for T cell mediated hypersensitivity · Serum specific IgE · tryptase concentration in blood serum (plasma) · basophil activation test (BAT) · cellular antigen stimulation test (CAST) - enzyme immunoassay (ELISA) · lymphocyte transformation test (LTT) · ELISPOT test · CD69 expression · skin tests skin prick tests · provocation tests · skin tests skin prick tests and/or photopatch tests · provocation tests The authors proposed a clear presentation of the procedures used in the diagnosis of allergic diseases/hypersensitivity in a separate group, and at the same time their update it in the International Classification of Health Interventions (ICHI). Joint forces of the European Academy of Allergy and Clinical Immunology (EAACI), World Allergy Organization (WAO), American Academy of Allergy Asthma and Immunology (AAAAI), Latin American Allergy, Asthma and Immunology Association (SLAAI), Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI) and the American College of Allergy, Asthma and Immunology (ACAAI) created the "Joint Allergy Academies". Thanks to international cooperation of allergy societies, an extensive two-page list of allergic diseases/hypersensitivity was presented, which, after consultation with the WHO, was included in the draft ICD- 11. Over the past seven years, a series of publications have been released, so that for the first time in the history of the ICD, allergic/hypersensitivity diseases had a completely separate chapter. The enormous amount of work done by Luciane Kase Tanno and Pascal Demoly resulted in the creation of the WHO Collaborating Centre WHO CC (2018) for the Scientific Classification of Allergic Diseases and Hypersensitivity at the Department of Pulmonology and Allergology of the University Hospital of Montpellier. WHO CC Montpellier is one of 25 WHO centres which collaborates in the international classifications and the only centre responsible for the allergic diseases. The WHO Montpellier Centre will be involved in promoting the implementation, workers training, application and updating of ICD classification to improve the quality of allergic diseases coding. The latest version of ICD-11 is available in English on the WHO official website. Intense work of the WHO CC resulted in the creation of a separate section titled: Allergic and hypersensitivity conditions in the newly created chapter Disorders of the Immune System in ICD-11. . The new rules for classifying and characterizing allergic diseases in the ICD-11 have undergone extensive functional and quality tests, which have confirmed the increased accuracy of allergy and hypersensitivity coding compared to the ICD-10. ICD-11 allows the diagnoses to be linked to a number of additional parameters by adding one or more extensions to the main code. The extensions are listed in Chapter X under the name of "Extension Codes". The WHO supported such a procedure, that will enable the appropriate linking of apparently different but important values for the course of allergic diseases, such as clinical symptoms severity, location or the cause of the disease. The WHO classification of death cause codes has also been revised by including anaphylaxis in the list of official causes of death, which will allow in future to include anaphylaxis in the official death records. This will improve the precision of mortality statistics and the analysis of related factors, e.g. aetiology ( 16). ICD-11 chapter 4 "Allergic diseases and hypersensitivity" Due to the various clinical manifestation of allergic diseases, a completely new subchapter entitled "Allergic or hypersensitivity conditions was created in the fourth chapter entitled "Diseases of immune system". In this chapter issues related to allergy/hypersensitivity (A/H) were divided into individual groups, and these, in turn, into subgroups that define specific diseases (Figure 1). Each of the subgroups has been significantly expanded, which allowed to assign the most common allergic diseases to a specific code, including rare diseases such as hereditary angioedema -HAE (4A00.1). Figure 1. ICD-11, chapter 4 - classification concerning allergic diseases. Allergic diseases have the codes of chapter four, but in this chapter we can also find diseases encoded in other chapters, like spontaneous urticaria, which can be found in subsection 4A82, but has the code EB00. The new version of ICD also includes codes for „skin or other sensitization tests” QA00.A and for allergen immunotherapy QA00. Thanks to the chapter "X", it is possible to extend the code with the severity of symptoms, the location of changes, as well as a specific allergen (fig.2). Figure 2. Allergens listed in ICD-11 chapter X . A particular attention was paid to the issue of anaphylaxis. In ICD-10, the anaphylaxis is included in Section T78, " Adverse effects, not elsewhere classified ", of the Chapter XIX, " Injury, poisoning and certain other consequences of external causes." In the updated version, the section on anaphylaxis (4A84) is significantly expanded , and include the types of anaphylaxis, the severity of the course and along with the indication of the causative agent.. Despite the significantly extensive database, the ICD-11 encoding seems to be more intuitive in comparison to the ICD-10. Using the new qualification will not require memorizing individual codes of diseases. For example, by entering the search terms "allergy" and "venom" , the full name of the disease with the suitable code will occur - "Allergic reaction to insect venom" - 4A85.3. There is also a possibility to complete the code by the course of the reaction to : systemic- 4A85.30 or cutaneous- 4A85.31. In addition, the expansion of the codes will reduce the current need to use the descriptions of individual disease in medical documentation. The ICD let us to follow the occurrence of the diseases, diagnose them, and also support the decision-making of the organizational health care systems in many countries, therefore any changes within the ICD are of great economic importance. Appropriate usage of codes for recording disorders is a key issue to prevent misclassification. The current ICD-10 classification has many limitations. The new, extended version ICD-11 will have a number of positive effects. More reliable classification will improve the quality of statistical and epidemiological analysis of allergic and hypersensitivity diseases Increase awareness of allergy and improve clinical management of allergic patients. It also significantly improve the work of medical specialists and enable better financing of health services. 4. Papadopoulos NG, Agache I, Bavbek S, et al. Research needs in allergy: an EAACI position paper, in collaboration with EFA. Clin Transl Allergy. 2012;2(1):21. Published 2012 Nov 2. doi:10.1186/2045-7022-2-21 5. Bernstein IL, Li JT, Bernstein DI, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008;100(3 Suppl 3):S1-S148. doi:10.1016/s1081-1206(10)60305-5 6. Muraro A, Werfel T, Hoffmann-Sommergruber K, et al. EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy. Allergy. 2014;69(8):1008-1025. doi:10.1111/all.12429 7. Mayorga C, Celik G, Rouzaire P, et al. In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy. 2016;71(8):1103-1134. doi:10.1111/all.12886 8. Tanno LK, Ganem F, Demoly P, Toscano CM, Bierrenbach AL. Undernotification of anaphylaxis deaths in Brazil due to difficult coding under the ICD-10. Allergy. 2012;67(6):783-789. doi:10.1111/j.1398-9995.2012.02829.x 9. Demoly P, Tanno LK, Akdis CA, et al. Global classification and coding of hypersensitivity diseases - An EAACI - WAO survey, strategic paper and review. Allergy. 2014;69(5):559-570. doi:10.1111/all.12386 10. Tanno LK, Calderon MA, Li J, Casale T, Demoly P; Joint Allergy Academies. Updating Allergy and/or Hypersensitivity Diagnostic Procedures in the WHO ICD-11 Revision. J Allergy Clin Immunol Pract. 2016;4(4):650-657. doi:10.1016/j.jaip.2016.01.015 11. Tanno LK, Calderon MA, Demoly P; Joint Allergy Academies. New Allergic and Hypersensitivity Conditions Section in the International Classification of Diseases-11. Allergy Asthma Immunol Res. 2016;8(4):383-388. doi:10.4168/aair.2016.8.4.383 15. Tanno LK, Calderon MA, Goldberg BJ, Akdis CA, Papadopoulos NG, Demoly P. Categorization of allergic disorders in the new World Health Organization International Classification of Diseases. Clin Transl Allergy. 2014;4:42. Published 2014 Nov 28. doi:10.1186/2045-7022-4-42 16. Tanno LK, Molinari N, Bruel S, et al. Field-testing the new anaphylaxis' classification for the WHO International Classification of Diseases-11 revision. Allergy. 2017;72(5):820-826. doi:10.1111/all.13093	3	18	6	0	0	6	0.28392	12	4,547
- 1 Classification - 2 Cause/etiology - 3 Diagnosis - 4 Treatment - 5 Prevention - 6 References Dyspepsia (from the Greek "δυς-" (Dys-), meaning hard or difficult, and "πέψη" (Pepse), meaning digestion) is chronic or recurrent pain or discomfort centered in the upper abdomen Discomfort, in this context, includes mild pain, upper abdominal fullness and feeling full earlier than expected with eating. It can be accompanied by bloating, belching, nausea or heartburn. It may be called indigestion. Heartburn is excluded from the definition of dyspesia in ICD 10, as it usually has a different cause and management pathway. When a patient has dyspepsia, but underlying disease is found, the patient is said to have non-ulcer dyspepsia or functional dyspepsia or idopathic dyspepsia. - ulcerlike - "Pain centered in the upper abdomen is the predominant (most bothersome) symptom." - dysmotilitylike - "An unpleasant or troublesome non-painful sensation (discomfort) centered in the upper abdomen is the predominant symptom; this sensation may be characterized by or associated with upper abdominal fullness, early satiety, bloating, or nausea." - Factor 1 - "characterized by nausea, vomiting, early satiety, and weight loss...associated with delayed emptying...younger age, female sex, and sickness behavior" - Factor 2 - "characterized by postprandial fullness and bloating...associated with delayed emptying" - Factor 3 - "characterized by pain symptoms and associated with gastric hypersensitivity and several psychosocial dimensions including medically unexplained symptoms and health-related quality of life dimensions". - Factor 4 - "characterized by belching, is also associated with hypersensitivity, but is unrelated to psychosocial dimensions." \|Patients referred to gastroenterologists for dyspesia\|\|Primary care patients with dyspepsia\|\|Volunteers with dyspepsia\|\|Volunteers without dyspepsia\|\|Volunteers without dyspepsia\|\|Referred patients in China\| \| Macroscopically normal \| Histologically normal by biopsy at EGD \| Macroscopic esophagitis 1 & 2) \|Hiatal hernia >2 cm by UGI\|\|40%\|\|26%\| \|Hiatal hernia by EGD\|\|3%\|\|3%\| \|Peptic ulcer disease (PUD)\|\|20%\|\|8%\|\|9%\|\|4%\|\|4%\| Non-ulcer dyspepsia (NUD) Nonulcer dyspepsia exists (functional dyspepsia) when esophagogastroduodenoscopy and other tests have excluded other diseases and the patient has the following Rome II criteria: At least 12 weeks, which need not be consecutive, within the preceding 12 months of: - Persistent or recurrent dyspepsia (pain or discomfort centered in the upper abdomen); and - No evidence of organic disease (including at upper endoscopy) that is likely to explain the symptoms; and - No evidence that dyspepsia is exclusively relieved by defecation or associated with the onset of a change in stool frequency or stool form (i.e., not irritable bowel). Possible causes of NUD The implied lack of organic disease may actually be incorrect as there may be physiological abnormalities that are too subtle for commonly used tests. For example, some patients may have gastric motor function or visceral sensitivity. Non-ulcer dyspepsia, when of acute onset, may be due to gastric dysmotor dysfunction following gastrointestinal infections. The role of H. pylori is not clear. Association with other diseases Psychiatric diagnoses are more prevalent among patients with normal endoscopies than abnormal endoscopies. History and physical examination The history and physical examination cannot reliably detect when organic disease underlies dypspepsia. Alarm features or red flags that may indicate serious underlying diseases are: - Age older than 55 years with new-onset dyspepsia - Family history of upper gastrointestinal cancer - Unintended weight loss - Gastrointestinal bleeding - Progressive dysphagia - Unexplained iron-deficiency anemia - Persistent vomiting - Palpable mass or lymphadenopathy - History of an previous ulcer - Age 50 or more - Pain better with food or milk (presumably identifies duodenal pathology) - Pain occurs < one hour after eating (presumably identifies gastric pathology) Regarding gastric cancer, helpful findings are anemia and persistence of symptoms. Identifying a psychiatric disorder may reduce the chance than a serious organic disorder is present. On physical examination, pallor of conjunctiva, nail-bed or palmar crease, or the absence of nail-bed blanching are predictive of significant anemia (hemoglobin less than 12 gm/dl). Complete blood count H. pylori testing Several studies indicate the need to test dyspeptic patients for H. pylori. One study found that by using "H. pylori serology and a hemoglobin reading in the evaluation of dyspeptic patients under 45 years of age, the need for endoscopy can be reduced by 55%." False negative tests Testing should be delayed for 2 weeks after stopping PPI use to avoid false negative breath test or a stool antigen test. Impact of testing In summary, test and treat may reduce symptoms at two months with no improvement at one year. "While early endoscopy offered some advantages 'Test and treat' was the most cost-effective strategy" according to a randomized controlled trial. In this trial, the relative benefit ratio of Helicobacter pylori serum testing for improvement at 2 months was 1.2 and, the relative benefit increase was 23.7%. In populations similar to those in this study which had a rate of benefit as measured by the improvement at 2 months of 59% without treatment, the number needed to treat is 7. There were no differences at 12 months. "Test and treat and acid suppression are equally cost effective in the initial management of dyspepsia" according to a randomized controlled trial. In this trial, the relative benefit ratio of Helicobacter pylori breath testing for no dyspepsia at one year was 1.1 and, the relative benefit increase was 5.9%. In populations similar to those in this study which had a rate of benefit as measured by the no dyspepsia at one year of 17% without treatment, the number needed to treat is 100. UGI as historic significance as good before EGD. Direct visualization by esophagogastroduodenoscopy(EGD) is very sensitive for peptic ulcer disease, but may not detect all possible underlying causes of dyspepsia. For example, gastroesophageal reflux disease that does not cause macroscopic esophagitis will be missed by esophagogastroduodenoscopy. For patients with positive Helicobacter pylori tests, obtaining endoscopy may be reasonable alternative to empiric antibiotics though less well studied. This strategy allows identification of patients with GERD and also may reduce discontinuing antibiotics due to adverse drug reactions. Many randomized controlled trials have compared empiric treatment (either for Helicobacter pylori or acid suppression), routine Helicobacter pylori testing, and routine esophagogastroduodenoscopy (EGD). These are summarized in a meta-analysis by the Cochrane Collaboration. Additional trials have been published since the review by the Cochrane. A meta-analysis of randomized controlled trials by the Cochrane Collaboration concluded "there is evidence that anti-secretory therapy may be effective in NUD" with a number needed to treat for PPIs of 10. Subsequent randomized controlled trials have had conflicting results reporting both benefit and no benefit. Stepping up therapy may be better than stepping down therapy. Prokinetic drugs include: - Serotonin-3 (5-HT3) receptor agonists (cisapride, mosapride) - Dopamine receptor antagonists (domperidone, metoclopramide, itopride) - Opiate agonists (trimebutine). Trimebutine also has antiserotonergic activity. The Cochrane Collaboration concluded "trials evaluating prokinetic therapy are difficult to interpret as the...[positive] result could have been due to publication bias.". More recently, a randomized controlled trial of itopride found that 100 mg three times per day benefited 17% of patients (number needed to treat is 6). Eradication of H. pylori - "Patients 55 years of age or younger without alarm features should receive Helicobacter pylori test and treat followed by acid suppression if symptoms remain" The Cochrane Collaboration concluded "small but statistically significant effect in H. pylori positive non-ulcer dyspepsia. The number needed to treat was 14. An economic model suggests this modest benefit may still be cost-effective but more research is needed." A more recent randomized controlled trial did not find a difference. The effect of eradication seems related to the presence of gastritis. Patients with antral predominant gastritis are more likely to improve whereas patients with corpus-predominant gastritis are less likely to improve. This may be due to antral erosions being due to hyperacidity the is corrected by treatment whereas corpus erosions are hypoacidic and treating this may increase the ability of the stomach to produce acid. 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PMID 11809180. - Chan FK, Sung JJ, Chung SC, et al (1997). "Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers". Lancet 350 (9083): 975–9. PMID 9329511. - Spiegel BM, Farid M, Dulai GS, Gralnek IM, Kanwal F (2006). "Comparing rates of dyspepsia with Coxibs vs NSAID+PPI: a meta-analysis". Am. J. Med. 119 (5): 448.e27–36. DOI:10.1016/j.amjmed.2005.11.020. PMID 16651060. Research Blogging. - Ford AC, Forman D, Bailey AG, Axon AT, Moayyedi P (2005). "A community screening program for Helicobacter pylori saves money: 10-year follow-up of a randomized controlled trial". Gastroenterology 129 (6): 1910–7. DOI:10.1053/j.gastro.2005.09.016. PMID 16344059. Research Blogging.	2	49	10	0	1	0	0.936147	11	6,507
Learn the definition of a screening colonoscopy and instructions for coding for screening colonoscopy and polyp removal in CPT and ICD-10-CM. You will also learn the appropriate use of modifier 33 and how it is applied in the following coding example. Name That Code! Question: A 60-year-old female patient presents to the outpatient surgery area for a screening colonoscopy. She has no signs or symptoms, nor any personal or family history of polyps or colorectal cancer. The surgeon inserts a flexible colonoscope into the rectum and advances it through the colon to the cecum. Two polyps are identified. A wire snare loop is slipped around each polyp and the loop is heated to shave off and cauterize the polyps. The mucosal surfaces are observed and no other abnormalities are found. The colonoscope is then removed. This is a non-Medicare patient. Assign the correct CPT code(s) and ICD-10-CM code(s). ICD-10-CM: Z12.11, K63.5 Colonoscopy With Polyp Removal What is a Colonoscopy? A colonoscopy is the examination of the entire colon, from the rectum to the cecum, and may include an examination of the terminal ileum or small intestine proximal to an anastomosis. A colonoscopy can help the physician determine the cause of symptoms such as bleeding from the anus, changes in bowel activity, pain in the abdomen, or unexplained weight loss. Anastomosis is the surgical connection between two structures. The connection is commonly created between tubular structures such as blood vessels or loops of intestine, according to the U.S National Library of Medicine/MedlinePlus. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIH), a screening colonoscopy is also performed in patients with no symptoms and is started at the age of 45 to look for colon polyps and cancer. If the patient has health problems or risk factors that put them at greater risk of developing colon cancer, the screening colonoscopy may be started at a younger age. Removal of Polyps During Colonoscopy (Video) The following video may help you better understand what happens during a colonoscopy and how polyps are removed. The snare technique is discussed. The documentation states that the patient is seen for a screening colonoscopy (no symptoms and no history). Two polyps are removed. A screening colonoscopy is considered a preventive service and is performed on a patient without symptoms. A non-Medicare patient with a screening colonoscopy is reporting using CPT conventions. Medicare patients receiving the same exam are reported using HCPCS codes G0105 (Colorectal cancer screening; colonoscopy on individual at high risk) or G0121 (Colorectal cancer screening; colonoscopy on individual not meeting the criteria for high risk). If polyps are removed during a screening colonoscopy, the appropriate combination CPT code should be assigned. Locate and Verify In the CPT coding manual Index, look up Colonoscopy, removal, polyp 44392, 44394, 45384-45385. - 44392, Colonoscopy through stoma; with removal of tumor(s), polyp(s), or other lesion(s) by hot biopsy forceps - 44394, Colonoscopy through stoma; with removal of tumor(s), polyp(s), or other lesion(s) by snare technique - 45384, Colonoscopy, flexible; with removal of tumor(s), polyp(s), or other lesion(s) by hot biopsy forceps - 45385, Colonoscopy, flexible; with removal of tumor(s), polyp(s), or other lesion(s) by snare technique The documentation indicates a flexible colonoscope was inserted and a wire snare loop was used to cauterize the polyps. That eliminates the possibility of codes 44392 and 44394. Verified in the Tabular, 45385 refers to Colonoscopy, flexible; with removal of tumor(s), polyp(s), or other lesion(s) by snare technique. Even though two polyps were removed in the snare technique, CPT code 45385 should only be reported once. Per AMA Guidelines: - Do not report 45385 in conjunction with 45390 for the same lesion - Do not report 45385 in conjunction with 45378 - For endoscopic mucosal resection, use 45390 Modifier 33, Preventive Services, took effect in 2011 to identify services that are not inherently preventive but are provided as a result of a preventive service. In the coding scenario above, the patient started out with a screening colonoscopy, and it was converted to a diagnostic colonoscopy due to the discovery of two polyps. Hence, modifier 33 should be appended to the therapeutic screening code for the colonoscopy and removal of polyps (45385-33). This modifier is only to be used for non-Medicare patients and tells the payor that the therapeutic procedure should be reimbursed without regard to a patient’s copayment or deductible. If the same procedure was performed on a Medicare patient, modifier PT (Colorectal cancer screening test; converted to diagnostic test or other procedure) would be appended to the CPT code. The use of modifier -33 would be incorrect in this situation. The CPT coding manual gives the following description for Modifier 33: “Preventive Services; When the primary purpose of the service is the delivery of an evidence-based service in accordance with a US Preventive Services Task Force A or B rating in effect and other preventive services identified in preventive services mandates (legislative or regulatory), the service may be identified by adding 33 to the procedure. For separately reported services specifically identified as preventive, the modifier should not be used.“ CPT code 45384 is incorrect because the code description indicates that hot biopsy forceps removed the polyps. Encounter for Screening Locate and Verify In the ICD-10-CM coding manual Index, look up Screening (for), colonoscopy Z12.11. Verified in the Tabular, the correct code is: Z12.11, Encounter for screening for malignant neoplasm of colon Encounter for screening colonoscopy NOS There are instructional notes at Z12: - Screening is the testing for disease or disease precursors in asymptomatic individuals so that early detection and treatment can be provided for those who test positive for the disease. - Use additional code to identify any family history of malignant neoplasm (Z80.-) - Excludes1: encounter for diagnostic examination-code to sign or symptom Additional notes provided at Z00-Z13 include: - Nonspecific abnormal findings disclosed at the time of these examinations are classified to categories R70-R94. - Excludes1: examinations related to pregnancy and reproduction (Z30-Z36, Z39.-) According to the ICD-10-CM Official Guidelines for Coding and Reporting: “Screening is the testing for disease or disease precursors in seemingly well individuals so that early detection and treatment can be provided for those who test positive for the disease (e.g., screening mammogram). The testing of a person to rule out or confirm a suspected diagnosis because the patient has some sign or symptom is a diagnostic examination, not a screening. In these cases, the sign or symptom is used to explain the reason for the test. A screening code may be a first-listed code if the reason for the visit is specifically the screening exam. It may also be used as an additional code if the screening is done during an office visit for other health problems. A screening code is not necessary if the screening is inherent to a routine examination, such as a pap smear done during a routine pelvic examination. Should a condition be discovered during the screening, then the code for the condition may be assigned as an additional diagnosis. The Z code indicates that a screening exam is planned. A procedure code is required to confirm that the screening was performed.” “The screening Z codes/categories: Z11 Encounter for screening for infectious and parasitic diseases Z12 Encounter for screening for malignant neoplasms Z13 Encounter for screening for other diseases and disorders except Z13.9, Encounter for screening, unspecified Z36 Encounter for antenatal screening for mother” A colon polyp forms on the lining of the colon and contains a small clump of cells. According to the Mayo Clinic, these polyps are usually harmless. However, they can develop into colon cancer at some point and may be fatal if not found in the earlier stages. Locate and Verify In the ICD-10-CM coding manual Index, look up Polyp, polypus, colon K63.5. Verified in the Tabular, our correct code is: K63.5, Polyp of colon - adenomatous polyp of colon (D12.-) - inflammatory polyp of colon (K51.4-) - polyposis of colon (D12.6) Note: K63.5 is the default code for a colon polyp. If further specificity is provided, such as the location of the polyp, you would assign a different code. Be sure to read all the notes listed for each code. There is an Excludes2 note to review at K00-K95 which indicates additional codes may need to be assigned. If you like this article, please share it.	4	9	14	0	2	16	0.675559	32	2,067
- Androgen insensitivity syndrome Androgen insensitivity syndrome Classification and external resources AIS results when the function of the androgen receptor (AR) is impaired. The AR protein (pictured) mediates the effects of androgens in the human body. ICD-10 E34.5 ICD-9 259.5 OMIM 312300 300068 DiseasesDB 29662 12975 eMedicine ped/2222 MeSH D013734 GeneReviews Androgen Insensitivity Syndrome Androgen insensitivity syndrome (AIS) is a condition that results in the partial or complete inability of the cell to respond to androgens. The unresponsiveness of the cell to the presence of androgenic hormones can impair or prevent the masculinization of male genitalia in the developing fetus, as well as the development of male secondary sexual characteristics at puberty, but does not significantly impair female genital or sexual development. As such, the insensitivity to androgens is only clinically significant when it occurs in genetic males (i.e. individuals with a Y-chromosome, or more specifically, an SRY gene). Clinical phenotypes in these individuals ranges from a normal male habitus with mild spermatogenic defect or reduced secondary terminal hair, to a full female habitus, despite the presence of a Y-chromosome. AIS is divided into three categories that are differentiated by the degree of genital masculinization: complete androgen insensitivity syndrome (CAIS) is indicated when the external genitalia is that of a normal female, mild androgen insensitivity syndrome (MAIS) is indicated when the external genitalia is that of a normal male, and partial androgen insensitivity syndrome (PAIS) is indicated when the external genitalia is partially, but not fully masculinized. - 1 Signs and symptoms - 2 Genetics - 3 Pathophysiology - 4 Diagnosis - 5 Management - 6 Epidemiology - 7 History - 8 References - 9 External links Signs and symptoms AIS is broken down into three classes based on phenotype: complete androgen insensitivity syndrome (CAIS), partial androgen insensitivity syndrome (PAIS), and mild androgen insensitivity syndrome (MAIS). A supplemental system of phenotypic grading that uses seven classes instead of the traditional three was proposed by pediatric endocrinologist Charmian A. Quigley et al. in 1995. The first six grades of the scale, grades 1 through 6, are differentiated by the degree of genital masculinization; grade 1 is indicated when the external genitalia is fully masculinized, grade 6 is indicated when the external genitalia is fully feminized, and grades 2 through 5 quantify four degrees of decreasingly masculinized genitalia that lie in the interim. Grade 7 is indistinguishable from grade 6 until puberty, and is thereafter differentiated by the presence of secondary terminal hair; grade 6 is indicated when secondary terminal hair is present, whereas grade 7 is indicated when it is absent. The Quigley scale can be used in conjunction with the traditional three classes of AIS to provide additional information regarding the degree of genital masculinization, and is particularly useful when the diagnosis is PAIS. The human androgen receptor (AR) is a protein encoded by a gene located on the proximal long arm of the X chromosome (locus Xq11-Xq12). The protein coding region consists of approximately 2,757 nucleotides (919 codons) spanning eight exons, designated 1-8 or A-H. Introns vary in size between 0.7 and 26 kb. Like other nuclear receptors, the androgen receptor protein consists of several functional domains: the transactivation domain (also called the transcription-regulation domain or the amino / NH2-terminal domain), the DNA-binding domain, the hinge region, and the steroid-binding domain (also called the carboxyl-terminal ligand-binding domain). The transactivation domain is encoded by exon 1, and makes up more than half of the AR protein. Exons 2 and 3 encode the DNA-binding domain, while the 5' portion of exon 4 encodes the hinge region. The remainder of exon 4 through exon 8 encodes the ligand binding domain. Trinucleotide satellite lengths and AR transcriptional activity The androgen receptor gene contains two polymorphic trinucleotide microsatellites in exon 1. The first microsatellite (nearest the 5' end) contains 8 to 60 repetitions of the glutamine codon "CAG" and is thus known as the polyglutamine tract. The second microsatellite contains 4 to 31 repetitions of the glycine codon "GGC" and is known as the polyglycine tract. The average number of repetitions varies by ethnicity, with Caucasians exhibiting an average of 21 CAG repeats, and Blacks 18. In men, disease states are associated with extremes in polyglutamine tract length; prostate cancer, hepatocellular carcinoma, and mental retardation are associated with too few repetitions, while spinal and bulbar muscular atrophy (SBMA) is associated with a CAG repetition length of 40 or more. Some studies indicate that the length of the polyglutamine tract is inversely correlated with transcriptional activity in the AR protein, and that longer polyglutamine tracts may be associated with male infertility and undermasculinized genitalia in men. However, other studies have indicated that no such correlation exists. A comprehensive meta-analysis of the subject published in 2007 supports the existence of the correlation, and concluded that these discrepancies could be resolved when sample size and study design are taken into account. Some studies suggest that longer polyglycine tract lengths are also associated with genital masculinization defects in men. Other studies find no such association. As of 2010, over 400 AR mutations have been reported in the AR mutation database, and the number continues to grow. Inheritance is typically maternal and follows an X-linked recessive pattern; individuals with a 46,XY karyotype will always express the mutant gene since they only have one X chromosome, whereas 46,XX carriers will be minimally affected. 30% of the time, the AR mutation is a spontaneous result, and is not inherited. Such de novo mutations are the result of a germ cell mutation or germ cell mosaicism in the gonads of one of the parents, or a mutation in the fertilized egg itself. In one study, it was found that 3 out of 8 de novo mutations occurred in the post-zygotic stage, leading to the estimate that up to one third of de novo mutations result in somatic mosaicism. It is worthwhile to note that not every mutation of the AR gene results in androgen insensitivity; one particular mutation occurs in 8 to 14 percent of genetic males, and is thought to adversely affect only a small number of individuals when other genetic factors are present. Some individuals with CAIS or PAIS do not have any AR mutations despite clinical, hormonal, and histological features sufficient to warrant an AIS diagnosis; up to 5% of women with CAIS do not have an AR mutation, as well as between 27% and 72% of individuals with PAIS. In one patient, it was shown that the underlying cause for presumptive PAIS was a mutant steroidogenic factor-1 (SF-1) protein. In another patient, it was shown that CAIS was the result of a deficit in the transmission of a transactivating signal from the N-terminal region of the normal androgen receptor to the basal transcription machinery of the cell. It was suggested that a coactivator protein interacting with the activation function 1 (AF-1) transactivation domain of the androgen receptor was deficient in this patient. The signal disruption could not be corrected by supplementation with any coactivators known at the time, nor was the absent coactivator protein characterized, which left some in the field unconvinced that a mutant coactivator would explain the mechanism of androgen resistance in CAIS or PAIS patients with a normal AR gene. Depending on the mutation, a person with a (46,XY karyotype) and AIS can have either a male (MAIS) or female (CAIS) phenotype, or may have genitalia that is only partially masculinized (PAIS). The gonads are testes regardless of phenotype due to the influence of the Y-chromosome. A 46,XY female thus does not have ovaries or a uterus, and can neither contribute an egg towards conception nor gestate a child. Several case studies of fertile 46,XY males with androgen insensitivity have been published, although this group is thought to be a minority. Additionally, some infertile males with MAIS have been able to conceive children after increasing their sperm count through the use of supplementary testosterone. A genetic male conceived by a man with androgen insensitivity would not receive his father's X chromosome, and thus would neither inherit nor carry the gene for the syndrome. A genetic female conceived in such a way would receive her father's X chromosome, and would thus become a carrier. Genetic females (46,XX karyotype) have two X chromosomes, and thus have two AR genes. A mutation in one (but not both) of the AR genes results in a minimally affected, fertile, female carrier. Some carriers have been noted to have slightly reduced body hair, delayed puberty, and / or tall stature, presumably due to skewed X-inactivation. A female carrier will pass the affected AR gene to her children 50% of the time. If the affected child is a genetic female, she too will be a carrier. An affected 46,XY child will have androgen insensitivity syndrome. A genetic female with mutations in both AR genes could theoretically result from the union of a fertile man with androgen insensitivity and a female carrier of the gene, or from de novo mutation. However, given the scarcity of fertile androgen insensitive men and low incidence of AR mutation, the chances of this occurrence is small. The phenotype of such an individual is a matter of speculation; as of 2010, no such documented case has been published. Correlation of genotype and phenotype Individuals with partial androgen insensitivity, unlike those with the complete or mild forms, present at birth with ambiguous genitalia, and the decision to raise the child as male or female is often not obvious. Unfortunately, it is often the case that little information regarding phenotype can be gleaned from precise knowledge of the AR mutation itself; it is well established that the same AR mutation may cause significant variation in the degree of masculinization in different individuals, even among members of the same family. Exactly what causes this variation is not entirely understood, although factors contributing to it could include the lengths of the polyglutamine and polyglycine tracts, sensitivity to and variations in the intrauterine endocrine milieu, the effect of coregulatory proteins that are active in Sertoli cells, somatic mosaicism, expression of the 5RD2 gene in genital skin fibroblasts, reduced AR transcription and translation from factors other than mutations in the AR coding region, an unidentified coactivator protein, enzyme deficiencies such as 21-hydroxylase deficiency, or other genetic variations such as a mutant steroidogenic factor-1 (SF-1) protein. The degree of variation, however, does not appear to be constant across all AR mutations, and is much more extreme in some. Missense mutations that result in a single amino acid substitution are known to produce the most phenotypic diversity. Androgens and the androgen receptor The effects that androgens have on the human body --- virilization, masculinization, anabolism, etc. --- are not brought about by androgens themselves, but rather are the result of androgens bound to androgen receptors; the androgen receptor mediates the effects of androgens in the human body. Likewise, under normal circumstances, the androgen receptor itself is inactive in the cell until androgen binding occurs. - Androgen enters the cell. - Only certain organs in the body, such as the gonads and the adrenal glands, produce the androgen testosterone. - Testosterone is converted into dihydrotestosterone, a chemically similar androgen, in cells containing the 5 alpha reductase enzyme. - Both androgens exert their influence through binding with the androgen receptor. - Androgen binds with the androgen receptor. - The androgen receptor is expressed ubiquitously throughout the tissues of the human body. - Before it binds with an androgen, the androgen receptor is bound to heat shock proteins. - These heat shock proteins are released upon androgen binding. - Androgen binding induces a stabilizing, conformational change in the androgen receptor. - The two zinc fingers of the DNA-binding domain are exposed as a result of this new conformation. - AR stability is thought to be aided by type II coregulators, which modulate protein folding and androgen binding, or facilitate NH2/carboxyl-terminal interaction. - The hormone-activated androgen receptor is phosphorylated. - Receptor phosphorylation can occur before androgen binding, although the presence of androgen promotes hyperphosphorylation. - The biological ramifications of receptor phosphorylation are unknown. - The hormone-activated androgen receptor translocates to the nucleus. - Homodimerization occurs. - Dimerization is mediated by the second (nearest the 3' end) zinc finger. - DNA binding to regulatory androgen response elements occurs. - Target genes contain (or are flanked by) transcriptional enhancer nucleotide sequences that interact with the first zinc finger. - These areas are called androgen response elements. - Coactivators are recruited by the AR. - Target gene transcription ensues. It is theoretically possible for certain mutant androgen receptors to function without androgens; in vitro studies have demonstrated that a mutant androgen receptor protein can induce transcription in the absence of androgen if its steroid binding domain is deleted. Conversely, the steroid-binding domain may act to repress the AR transactivation domain, perhaps due to the AR's unliganded conformation. Androgens in fetal development Human embryos develop similarly for the first six weeks, regardless of genetic sex (46,XX or 46,XY karyotype); the only way to tell the difference between 46,XX or 46,XY embryos during this time period is to look for Barr bodies or a Y-chromosome. The gonads begin as bulges of tissue called the genital ridges at the back of the abdominal cavity, near the midline. By the fifth week, the genital ridges differentiate into an outer cortex and an inner medulla, and are called indifferent gonads. By the sixth week, the indifferent gonads begin to differentiate according to genetic sex. If the karyotype is 46,XY, testes develop due to the influence of the Y chromosome’s SRY gene. This process does not require the presence of androgen, nor a functional androgen receptor. Until approximately the seventh week of development, the embryo has indifferent sex accessory ducts, which consist of two pairs of ducts: the Müllerian ducts and the Wolffian ducts. The testes secrete anti-Müllerian hormone around this time to suppress the development of the Müllerian ducts, and cause their degeneration. Without this anti-Müllerian hormone, the Müllerian ducts develop into the female internal genitalia (uterus, cervix, fallopian tubes, and upper vaginal barrel). Unlike the Müllerian ducts, the Wolffian ducts will not continue to develop by default. In the presence of testosterone and functional androgen receptors, the Wolffian ducts develop into the epididymides, vasa deferentia, and seminal vesicles. If the testes fail to secrete testosterone, or the androgen receptors do not function properly, the Wolffian ducts degenerate. Masculinization of the external genitalia (the penis, penile urethra, and scrotum), as well as the prostate, are dependent on the androgen dihydrotestosterone. Testosterone is converted into dihydrotestosterone by the 5-alpha reductase enzyme. If this enzyme is absent or deficient, then dihydrotestosterone will not be created, and the external male genitalia will not develop properly. As is the case with the internal male genitalia, a functional androgen receptor is needed in order for dihydrotestosterone to regulate the transcription of target genes involved in development. Pathogenesis of Androgen Insensitivity Syndrome Mutations in the androgen receptor gene can cause problems with any of the steps involved in androgenization, from the synthesis of the androgen receptor protein itself, through the transcriptional ability of the dimerized, androgen-AR complex. AIS can result if even one of these steps is significantly disrupted, as each step is required in order for androgens to successfully activate the AR and regulate gene expression. Exactly which steps a particular mutation will impair can be predicted, to some extent, by identifying the area of the AR in which the mutation resides. This predictive ability is primarily retrospective in origin; the different functional domains of the AR gene have been elucidated by analyzing the effects of specific mutations in different regions of the AR. For example, mutations in the steroid binding domain have been known to affect androgen binding affinity or retention, mutations in the hinge region have been known to affect nuclear translocation, mutations in the DNA-binding domain have been known to affect dimerization and binding to target DNA, and mutations in the transactivation domain have been known to affect target gene transcription regulation. Unfortunately, even when the affected functional domain is known, it is difficult to predict the phenotypical consequences of a particular mutation (see Correlation of genotype and phenotype). Some mutations can adversely impact more than one functional domain. For example, a mutation in one functional domain can have deleterious effects on another by altering the way in which the domains interact. A single mutation can affect all downstream functional domains if a premature stop codon or framing error results; such a mutation can result in a completely unusable (or unsynthesizable) androgen receptor protein. The steroid binding domain is particularly vulnerable to the effects of a premature stop codon or framing error, since it occurs at the end of the gene, and its information is thus more likely to be truncated or misinterpreted than other functional domains. Other, more complex relationships have been observed as a consequence of mutated AR; some mutations associated with male phenotypes have been linked to male breast cancer, prostate cancer, or in the case of spinal and bulbar muscular atrophy, disease of the central nervous system. The form of breast cancer that is seen in some men with partial androgen insensitivity syndrome is caused by a mutation in the AR's DNA-binding domain. It has been hypothesized that this mutation causes a disturbance of the AR's target gene interaction that allows it to act at certain additional targets, possibly in conjunction with the estrogen receptor protein, to cause cancerous growth. The etiology of spinal and bulbar muscular atrophy (SBMA) demonstrates that even the mutant AR protein itself can result in pathology. The trinucleotide repeat expansion of the polyglutamine tract of the AR gene that is associated with SBMA results in the synthesis of a misfolded AR protein that the cell fails to properly proteolyze and disperse. These misfolded AR proteins form aggregates in the cell cytoplasm and nucleus. Over the course of 30 to 50 years, these aggregates accumulate and have a cytotoxic effect, eventually resulting in the neurodegenerative symptoms associated with SBMA. The phenotypes that result from the insensitivity to androgens are not unique to AIS, and thus the diagnosis of AIS requires thorough exclusion of other causes. Clinical findings indicative of AIS include the presence of a short vagina or undermasculinized genitalia, partial or complete regression of Müllerian structures, bilateral nondysplastic testes, and impaired spermatogenesis and / or virilization. Laboratory findings include a 46,XY karyotype and normal or elevated postpubertal testosterone, luteinizing hormone, and estradiol levels. The androgen binding activity of genital skin fibroblasts is typically diminished, although exceptions have been reported. Conversion of testosterone to dihydrotestosterone may be impaired. The diagnosis of AIS is confirmed if androgen receptor gene sequencing reveals a mutation, although not all individuals with AIS (particularly PAIS) will have an AR mutation (see Other Causes). Each of the three types of AIS --- complete, partial, and mild --- has a different list of differential diagnoses to consider. Depending on the form of AIS that is suspected, the list of differentials can include: - Chromosomal anomalies: - Androgen biosynthetic dysfunction in 46,XY individuals: - Luteinizing hormone (LH) receptor mutations - Smith-Lemli-Opitz syndrome (associated with mental retardation) - Lipoid congenital adrenal hyperplasia - 3β-hydroxysteroid dehydrogenase 2 deficiency - 17α-hydroxylase deficiency - 17,20 lyase deficiency - 17β-hydroxysteroid dehydrogenase deficiency - 5α-reductase deficiency - Androgen excess in 46,XX individuals: - 21-hydroxylase deficiency - 3β-hydroxysteroid dehydrogenase 2 deficiency - Cytochrome P450 oxidoreductase deficiency (disorder in mother causes 46,XX fetal virilization) - 11β-hydroxylase deficiency - Aromatase deficiency - Glucocorticoid receptor mutations - Maternal virilizing tumor (e.g. luteoma) - Increased androgen exposure in utero, not otherwise specified (e.g. androgenic drugs) - Mayer-Rokitansky-Küster-Hauser syndrome (46,XX karyotype) - Swyer syndrome (46,XY karyotype) - XX gonadal dysgenesis (46,XX karyotype) - Leydig cell agenesis or hypoplasia, not otherwise specified (46,XY karyotype) - Absent (vanishing) testes syndrome - Ovotesticular DSD - Testicular DSD (i.e. 46,XX sex reversal) - Teratogenic causes (e.g. estrogens, antiestrogens) - Other causes: - Frasier syndrome (associated with progressive glomerulopathy) - Denys-Drash syndrome (associated with nephropathy and Wilms tumor) - WAGR syndrome (associated with Wilms tumor and aniridia) - McKusick-Kaufman syndrome (associated with postaxial polydactyly) - Robinow syndrome (associated with dwarfism) - Aarskog-Scott syndrome (associated with facial anomalies) - Hand-foot-genital syndrome (associated with limb malformations) - Popliteal pterygium syndrome (associated with extensive webbing behind knees) - Kallmann syndrome (often associated with anosmia) - Hypospadias not otherwise specified - Cryptorchidism not otherwise specified - vaginal atresia not otherwise specified Management of AIS is currently limited to symptomatic management; methods to correct a malfunctioning androgen receptor protein that result from an AR gene mutation are not currently available. Areas of management include sex assignment, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, and genetic and psychological counseling. Estimates for the incidence of androgen insensitivity syndrome are based on a relatively small population size, and thus are known to be imprecise. CAIS is estimated to occur in 1 out of every 20,400 46,XY births. A nationwide survey in The Netherlands based on patients with genetic confirmation of the diagnosis estimates that the minimal incidence of CAIS is 1 in 99,000. The incidence of PAIS is estimated to be 1 in 130,000. Due to its subtle presentation, MAIS is not typically investigated except in the case of male infertility, and thus its true prevalence is unknown. Recorded descriptions of the effects of androgen insensitivity syndrome date back for hundreds of years, although significant understanding of its underlying histopathology would not occur until the 1950s. The taxonomy and nomenclature associated with androgen insensitivity went through a significant evolution that paralleled this understanding. Timeline of major milestones - 1950: Lawson Wilkins administers daily methyltestosterone to a 46,XY female patient, who shows no signs of virilization. His experiment is the first documented demonstration of the pathophysiology of androgen insensitivity syndrome. - 1970: Mary F. Lyon and Susan Hawkes report that a gene on the X chromosome caused complete insensitivity to androgens in mice. - 1981: Barbara Migeon et al. narrow down the locus of the human androgen receptor gene (or a factor controlling the androgen receptor gene) to somewhere between Xq11 and Xq13. - 1988: The human androgen receptor gene is first cloned and partially analyzed by multiple parties. Terry Brown et al. report the first mutations proven to cause AIS. - 1989: Terry Brown et al. reports the exact locus of the AR gene (Xq11-Xq12), and Dennis Lubahn et al. publishes its intron-exon boundaries. - 1994: The androgen receptor gene mutations database is created to provide a comprehensive listing of mutations published in journals and conference proceedings. The first descriptions of the effects of androgen insensitivity appeared in the medical literature as individual case reports or as part of a comprehensive description of intersex physicalities. In 1839, Scottish obstetrician Sir James Young Simpson published one such description in an exhaustive study of intersexuality that has been credited with advancing the medical community's understanding of the subject. Simpson's system of taxonomy, however, was far from the first; taxonomies / descriptions for the classification of intersexuality were developed by Italian physician and physicist Fortuné Affaitati in 1549, French surgeon Ambroise Paré in 1573, French physician and sexology pioneer Nicolas Venette in 1687 (under the pseudonym Vénitien Salocini), and French Zoologist Isidore Geoffroy St. Hilaire in 1832. All five of the aforementioned authors used the colloquial term "hermaphrodite" as the foundation of their taxonomies, although Simpson himself questioned the propriety of the word in his publication. Use of the word "hermaphrodite" in the medical literature has persisted to this day, although its propriety is still in question. An alternative system of nomenclature has been recently suggested, but the subject of exactly which word or words should be used in its place still one of much debate. "Pseudohermaphroditism" has, until very recently, been the term used in the medical literature to describe the condition of an individual whose gonads and karyotype do not match the external genitalia in the gender binary sense. For example, 46,XY individuals that have a female phenotype, but also have testes instead of ovaries --- a group that includes all individuals with complete androgen insensitivity (CAIS), as well as some individuals with partial androgen insensitivity (PAIS) --- are classified as having "male pseudohermaphroditism," while individuals with both an ovary and a testis (or at least one ovotestis) are classified as having "true hermaphroditism.". Usage of the word in the medical literature predates the discovery of the chromosome, and thus its definition has not always taken karyotype into account when determining an individual's sex. Previous definitions of "pseudohermaphroditism" relied on perceived inconsistencies between the internal and external organs; the "true" sex of an individual was determined by the internal organs, and the external organs determined the "perceived" sex of an individual. German-Swiss pathologist Edwin Klebs is sometimes noted for using the word "pseudohermaphroditism" in his taxonomy of intersexuality in 1876, although the word is clearly not his invention as is sometimes reported; the history of the word "pseudohermaphrodite," and the corresponding desire to separate "true" hermaphrodites from "false," "spurious," or "pseudo" hermaphrodites, dates back to at least 1709, when Dutch anatomist Frederik Ruysch used it in a publication describing a subject with testes and a mostly female phenotype. "Pseudohermaphrodite" also appeared in the Acta Eruditorum later that same year, in a review of Ruysch's work. There is also evidence that the word was already being used by the German and French medical community long before Klebs used it; German physiologist Johannes Peter Müller equated "pseudohermaphroditism" with a sub-class of hermaphroditism from St. Hilaire's taxonomy in a publication dated 1834, and by the 1840s "pseudo-hermaphroditism" was appearing in several French and German publications, including dictionaries. In 1953, American gynecologist John Morris provided the first full description of what he called "testicular feminization syndrome" based on 82 cases compiled from the medical literature, including 2 of his own patients. The term "testicular feminization" was coined to reflect Morris' observation that the testicles in these patients produced a hormone that had a feminizing effect on the body, a phenomenon that is now understood to be due to the inaction of androgens, and subsequent aromatization of testosterone into estrogen. A few years before Morris published his landmark paper, Lawson Wilkins had shown through his own experiments that unresponsiveness of the target cell to the action of androgenic hormones was a cause of "male pseudohermaphroditism". Wilkins' work, which clearly demonstrated the lack of a therapeutic effect when 46,XY women were treated with androgens, caused a gradual shift in nomenclature from "testicular feminization" to "androgen resistance". A distinct name has been given to many of the various presentations of androgen insensitivity syndrome, such as Reifenstein syndrome (1947), Goldberg-Maxwell syndrome (1948), Morris' syndrome (1953), Gilbert-Dreyfus syndrome (1957), Lub's syndrome (1959), "incomplete testicular feminization" (1963), Rosewater syndrome (1965), and Aiman's syndrome (1979). Since it was not understood that these different presentations were all caused by the same set of mutations in the androgen receptor gene, a unique name was given to each new combination of symptoms, resulting in a complicated stratification of seemingly disparate disorders. Over the last 60 years, as reports of strikingly different phenotypes were reported to occur even among members of the same family, and as steady progress was made towards the understanding of the underlying molecular pathogenesis of AIS, it has been demonstrated that these disorders are different phenotypic expressions of one syndrome caused by molecular defects in the androgen receptor gene. Androgen insensitivity syndrome (AIS) is now the accepted terminology for the syndromes resulting from unresponsiveness of the target cell to the action of androgenic hormones. AIS is broken down into three classes based on phenotype: complete androgen insensitivity syndrome (CAIS), partial androgen insensitivity syndrome (PAIS), and mild androgen insensitivity syndrome (MAIS). CAIS encompasses the phenotypes previously described by "testicular feminization," Morris' syndrome, and Goldberg-Maxwell syndrome; PAIS includes Reifenstein syndrome, Gilbert-Dreyfus syndrome, Lub's syndrome, "incomplete testicular feminization," and Rosewater syndrome; and MAIS includes Aiman's syndrome. The more virilized phenotypes of AIS have sometimes been described as "undervirilized male syndrome," "infertile male syndrome," "undervirilized fertile male syndrome," etc., before evidence was reported that these conditions were caused by mutations in the androgen receptor gene. 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PMID 9239727. - Androgen Insensitivity Syndrome at NIH/UW GeneTests - Online 'Mendelian Inheritance in Man' (OMIM) Androgen Insensitivity Syndrome -300068,313700 - An Australian parent/patient booklet on CAIS - The Secret of My Sex news article - Women With Male DNA All Female news article at ABCnews.com - AIS Support Group AISSG (UK and International) - AIS-DSD Support Group for Women & Families - AIS Support Group (Australasia) - Intersex Support Forums (US and International) Endocrine pathology: endocrine diseases (E00–E35, 240–259) Pancreas/ pituitary axesHypothalamusPituitaryThyroidEndemic goitre · Toxic nodular goitre · Toxic multinodular goiter Height Multiple Sex linkage: X-linked disorders X-linked recessive Immune Hematologic Endocrine Metabolicmineral: Menkes disease/Occipital horn syndrome Nervous system X-Linked mental retardation: Coffin–Lowry syndrome · MASA syndrome · X-linked alpha thalassemia mental retardation syndrome · Siderius X-linked mental retardation syndromeCharcot–Marie–Tooth disease (CMTX2-3) · Pelizaeus–Merzbacher disease · SMAX2 Skin and related tissue Neuromuscular Urologic Bone/tooth No primary system X-linked dominant Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies (1) Basic domains (2) Zinc finger 2.1 (Intracellular receptor): Thyroid hormone resistance · Androgen insensitivity syndrome (PAIS, MAIS, CAIS) · Kennedy's disease · PHA1AD pseudohypoaldosteronism · Estrogen insensitivity syndrome · X-linked adrenal hypoplasia congenita · MODY 1 · Familial partial lipodystrophy 3 · SF1 XY gonadal dysgenesis 2.2: Barakat syndrome · Tricho–rhino–phalangeal syndrome 2.3: Greig cephalopolysyndactyly syndrome/Pallister-Hall syndrome · Denys–Drash syndrome · Duane-radial ray syndrome · MODY 7 · MRX 89 · Townes–Brocks syndrome · Acrocallosal syndrome · Myotonic dystrophy 22.5: Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1: ARX (Ohtahara syndrome, Lissencephaly X2) · HLXB9 (Currarino syndrome) · HOXD13 (SPD1 Synpolydactyly) · IPF1 (MODY 4) · LMX1B (Nail–patella syndrome) · MSX1 (Tooth and nail syndrome, OFC5) · PITX2 (Axenfeld syndrome 1) · POU4F3 (DFNA15) · POU3F4 (DFNX2) · ZEB1 (Posterior polymorphous corneal dystrophy 3, Fuchs' dystrophy 3) · ZEB2 (Mowat-Wilson syndrome) 3.3: FOXC1 (Axenfeld syndrome 3, Iridogoniodysgenesis, dominant type) · FOXC2 (Lymphedema–distichiasis syndrome) · FOXE1 (Bamforth–Lazarus syndrome) · FOXE3 (Anterior segment mesenchymal dysgenesis) · FOXF1 (ACD/MPV) · FOXI1 (Enlarged vestibular aqueduct) · FOXL2 (Premature ovarian failure 3) · FOXP3 (IPEX)3.5: IRF6 (Van der Woude syndrome, Popliteal pterygium syndrome) (4) β-Scaffold factors with minor groove contacts 4.2: Hyperimmunoglobulin E syndrome 4.3: Holt-Oram syndrome · Li-Fraumeni syndrome · Ulnar–mammary syndromeCleidocranial dysostosis (0) Other transcription factors0.6: Kabuki syndrome Ungrouped Transcription coregulators Wikimedia Foundation. 2010.	2	93	27	0	10	3	0.894482	40	20,879
Cryoablation is a process that uses extreme cold to destroy tissue. Cryoablation is performed using hollow needles (cryoprobes) through which cooled, thermally conductive, fluids are circulated. Cryoprobes are positioned adjacent to the target in such a way that the freezing process will destroy the diseased tissue. Once the probes are in place, the attached cryogenic freezing unit removes heat from ("cools") the tip of the probe and by extension from the surrounding tissues. Animated GIF showing cryoablation of mass in right liver lobe using two probes. Time elapsed is approximately 30 minutes. \|ICD-9-CM\|\|37.33, 37.34, 60.62\| Ablation occurs in tissue that has been frozen by at least three mechanisms: - formation of ice crystals within cells thereby disrupting membranes, and interrupting cellular metabolism among other processes; - coagulation of blood thereby interrupting bloodflow to the tissue in turn causing ischemia and cell death; and - induction of apoptosis, the so-called programmed cell death cascade. The most common application of cryoablation is to ablate solid tumors found in the lung, liver, breast, kidney and prostate. The use in prostate and renal cryoablation are the most common. Although sometimes applied in cryosurgery through laparoscopic or open surgical approaches, most often cryoablation is performed percutaneously (through the skin and into the target tissue containing the tumor) by a medical specialist, such as an interventional radiologist. The term is from cryo- + ablation. Prostate cryoablation is moderately effective but, as with any prostate removal process, also can result in impotence. Prostate cryoablation is used in three patient categories: - as primary therapy in patients for whom sexual function is less important or who are poor candidates for radical retropubic prostatectomy (RRP, surgical removal of the prostate); - as salvage therapy in patients who have failed brachytherapy (the use of implanted radioactive "seeds" placed within the prostate) or external beam radiation therapy (EBRT); and - focal therapy for smaller, discrete tumors in younger patients. Cryoablation has been explored as an alternative to radiofrequency ablation in the treatment of moderate to severe pain in people with metastatic bone disease. The area of tissue destruction created by this technique can be monitored more effectively by CT than RFA, a potential advantage when treating tumors adjacent to critical structures. Cryoablation for breast cancer is typically only possible for small tumors. Often surgery is used following cryoablation. As of 2014 more research is required before it can replace lumpectomy. Another type of cryoablation is used to restore normal electrical conduction by freezing tissue or heart pathways that interfere with the normal distribution of the heart’s electrical impulses. Cryoablation is used in two types of intervention for the treatment of arrhythmias: (1) catheter-based procedures and (2) surgical operations. A catheter is a very thin tube that is inserted into a vein in the patient’s leg and threaded to the heart where it delivers energy to treat the patient’s arrhythmia. In surgical procedures, a flexible probe is used directly on an exposed heart to apply the energy that interrupts the arrhythmia. By cooling the tip of a cryoablation catheter (cardiology) or probe (heart surgery) to sub-zero temperatures, the cells in the heart responsible for conducting the arrhythmia are altered so that they no longer conduct electrical impulses. In this procedure which has been approved by the U.S. Food and Drug Administration (FDA), an ultrasound-guided probe is inserted into the fibroadenoma and extremely cold temperatures are then used to destroy the abnormal cells. Over time the cells are reabsorbed into the body. The procedure can be performed in a doctor's office setting with local anesthesia and leaves very little scarring compared to open surgical procedures. Different catheter-based ablation techniques may be used and they generally fall into two categories: (1) cold-based procedures where tissue cooling is used to treat the arrhythmia, and (2) heat-based procedures where high temperature is used to alter the abnormal conductive tissue in the heart. Cold temperatures are used in cryoablation to chill or freeze cells that conduct abnormal heart rhythms. The catheter removes heat from the tissue to cool it to temperatures as low as -75 °C. This causes localized scarring, which cuts undesired conduction paths. This is a much newer treatment for supraventricular tachycardia (SVT) involving the atrioventicular (AV) node directly. SVT involving the AV node is often a contraindication for using radiofrequency ablation because of the risk of injuring the AV node, forcing patients to receive a permanent pacemaker. With cryoablation, areas of tissue can be mapped by limited, reversible, freezing (e.g., to -10 C). If the result is undesirable, the tissue can be rewarmed without permanent damage. Otherwise, the tissue can be permanently ablated by freezing it to a lower temperature (e.g., -73 C). This therapy has revolutionized AV nodal reentrant tachycardia (AVNRT) and other AV nodal tachyarrhythmias. It has allowed people who were otherwise not a candidate for radiofrequency ablation to have a chance at having their problem cured. This technology was developed at The Montreal Heart institute in the late 1990s. The therapy was successfully adopted in Europe in 2001, and in the USA in 2004 following the "Frosty Trial". In 2004, the technology was pioneered in the midwest United States at Miami Valley Hospital in Dayton, Ohio by Mark Krebs, MD, FACC, Matthew Hoskins, RN, BSN and Ken Peterman, RN, BSN. These electrophysiology experts were successful in curing the first 12 candidates in their facility. Cryoablation for AVNRT and other arrhythmias do have some drawbacks. A recent study concluded that procedure times are slightly higher on average for cryoablation than for traditional radio-frequency (heat-based) ablations. Also, higher rate of equipment failures were recorded using this technique. Finally, even though short term success rate is equivalent to RF treatments, cryoablation appears to have a significantly higher long term recurrence rate. Cryotherapy is able to produce a temporary electrical block by cooling down the tissue believed to be conducting the arrhythmia. This allows the physician to make sure this is the right site before permanently disabling it. The ability to test a site in this way is referred to as site testing or cryomapping. When ablating tissue near the AV node (a special conduction center that carries electrical impulses from the atria to the ventricles), there is a risk of producing heart block – that is, normal conduction from the atria cannot be transmitted to the ventricles. Freezing tissue near the AV node is less likely to provoke irreversible heart block than ablating it with heat. As in catheter-based procedures, techniques using heating or cooling temperatures may be used to treat arrhythmias during heart surgery. Techniques also exist where incisions are used in the open heart to interrupt abnormal electrical conduction (Maze procedure). Cryosurgery involves the use of freezing techniques for the treatment of arrhythmias during surgery. A physician may recommend cryosurgery being used during the course of heart surgery as a secondary procedure to treat any arrhythmia that was present or that may appear during the primary openchest procedure. The most common heart operations in which cryosurgery may be used in this way are mitral valve repairs and coronary artery bypass grafting. During the procedure, a flexible cryoprobe is placed on or around the heart and delivers cold energy that disables tissue responsible for conducting the arrhythmia. Cryoimmunotherapy is an oncological treatment for various cancers that combines cryoablation of tumor with immunotherapy treatment. In-vivo cryoablation of a tumor, alone, can induce an immunostimulatory, systemic anti-tumor response, resulting in a cancer vaccine – the abscopal effect. However, cryoablation alone may produce an insufficient immune response, depending on various factors, such as high freeze rate. Combining cryotherapy with immunotherapy enhances the immunostimulating response and has synergistic effects for cancer treatment. The use of cold for pain relief and as an anti-inflammatory has been known since the time of Hippocrates (460–377 B.C). Since then there have been numerous accounts of ice used for pain relief including from the Ancient Egyptians and Avicenna of Persia (AD 982–1070). Since 1899, Dr. Campbell White used refrigerants for treating a variety of conditions, including: lupus erythematosus, herpes zoster, chancroid, naevi, warts, varicose leg ulcers, carbuncles, carcinomas and epitheliomas. De Quervain successfully used of carbonic snow to treat bladder papillomas and bladder cancers in 1917. Dr Irving S Cooper, in 1913, progressed the field of cryotherapy by designing a liquid nitrogen probe capable of achieving temperatures of -196 °C, and utilizing it to treat of Parkinson's disease and previously inoperable cancer. Cooper's cryoprobe advanced the practice of cryotherapy, which led to growing interest and practice of cryotherapy. In 1964, Dr. Cahan successfully used his liquid nitrogen probe invention to treat uterine fibroids and cervical cancer. Cryotherapy continued to advance with Dr. Amoils developing a liquid nitrogen probe capable of achieving cooling expansion, in 1967. With the technological cryoprobe advancements in the 1960s, came wider acceptance and practice of cryotherapy. Since the 1960s, liver, prostate, breast, bone, and other cancers were being treated with cryoablation in many parts of the world. Japanese physician Dr. Tanaka began treating metastatic breast cancer cryoablation in 1968. For the next three decades, Dr. Tanaka successfully treated small and localized as well as advanced and unresectable breast cancer with minimally invasive cryoablation. All of Dr. Tanaka's breast cancer cases were considered incurable: advanced, unresectable, and resistant to radiotherapy, chemotherapy, and endocrine therapy. At the same time, physicians, including Dr. Ablin and Dr. Gage, started utilizing cryoablation for the treatment of prostate and bone cancer. The 1980s and 1990s saw dramatic advancement in apparatus and imaging techniques, with the introduction of CMS Cryoprobe, and Accuprobe. CT, MRI, ultrasound guided cryoprobes became available and improved the capabilities of cryoprobes in treatment. Excited by the latest advancements in cryotherapy, China embraced cryotherapy in the 1990s, to treat many oncological conditions. With the benefits well-established, the FDA approved the treatment of prostate cancer with cryoablation in 1998. - Callstrom, Matthew R.; Dupuy, Damian E.; Solomon, Stephen B.; Beres, Robert A.; Littrup, Peter J.; Davis, Kirkland W.; Paz-Fumagalli, Ricardo; Hoffman, Cheryl; Atwell, Thomas D. (2013-03-01). "Percutaneous image-guided cryoablation of painful metastases involving bone". Cancer. 119 (5): 1033–1041. doi:10.1002/cncr.27793. ISSN 1097-0142. PMC 5757505. PMID 23065947. - El Dib, R; Touma, NJ; Kapoor, A (August 2012). "Cryoablation vs radiofrequency ablation for the treatment of renal cell carcinoma: a meta-analysis of case series studies". BJU International. 110 (4): 510–6. doi:10.1111/j.1464-410x.2011.10885.x. PMID 22304329. - Sabel, MS (July 2014). "Nonsurgical ablation of breast cancer: future options for small breast tumors". Surgical Oncology Clinics of North America. 23 (3): 593–608. doi:10.1016/j.soc.2014.03.009. PMID 24882353. - Medical Dictionary - WebMD – Cryotherapy Shrinks Benign Breast Lumps - Nov. 2010 German CYRANO study (Cryoablation Versus Radiofrequency Energy for the Ablation of Atrioventricular Nodal Reentrant Tachycardia) - Sidana Abhinav (2014). "Cancer immunotherapy using tumor cryoablation". Immunotherapy. 6 (1): 85–93. doi:10.2217/imt.13.151. PMID 24341887. - With improvements in breast imaging and image-guided interventions, there is interest in ablative techniques for breast cancer. Cryosurgery initiates inflammation and leaves tumor-specific antigens intact, which may induce an anti-tumor immune response.Tarkowski R, Rzaca M (2005). "Immunologic response to cryoablation of breast cancer". Gland Surg. 3 (2): 88–93. doi:10.3978/j.issn.2227-684X.2014.03.04. PMC 4115762. PMID 25083502. - Haen SP, Pereira PL, Salih HR, Rammensee HG, Gouttefangeas C (2011). "More Than Just Tumor Destruction: Immunomodulation by Thermal Ablation of Cancer". Clin Dev Immunol. 2011: 1–19. doi:10.1155/2011/160250. PMC 3254009. PMID 22242035. - Cooper (2001). "The History of Cryosurgery". J R Soc Med. 94 (4): 196–201. PMC 1281398. PMID 11317629. - Trescott (2003). "Cryoanalgesia in Interventional Pain Management". Pain Physician. 6 (3): 345–60. PMID 16880882. - Gage AA (1998). "History of cryosurgery". Semin Surg Oncol. 14 (2): 99–109. doi:10.1002/(sici)1098-2388(199803)14:2<99::aid-ssu2>3.0.co;2-1. PMID 9492880. - Freiman, Anatoli; Bsc, Nathaniel Bouganim (2005). "History of cryotherapy". Dermatology Online Journal. 11 (2). - Cooper SM, Dawber RP (2001). "The history of cryosurgery". J R Soc Med. 94 (4): 196–201. PMC 1281398. PMID 11317629. - Richard J. Ablin (1998). "The Use of Cryosurgery for Breast Cancer". Arch Surg. 133: 106. doi:10.1001/archsurg.133.1.106. - Marcove RC, Miller TR (1969). "The treatment of primary and metastatic localized bone tumors by cryosurgery". Surg Clin North Am. 49 (2): 421–30. doi:10.1016/s0039-6109(16)38799-0. PMID 5774987. - R. J. Ablin; et al. (1971). "Prospects for Cryo-Immunotherapy in Cases of Metastasizing Carcinoma of the Prostate". Cryobiology. 8 (3): 271–79. doi:10.1016/0011-2240(71)90050-2. - Geisler, Eliezer; Heller, Ori (2012). Management of Medical Technology: Theory, Practice and Cases. p. 281. ISBN 9781461555193. - Tumor treatment through cryotherapy was first invented by Americans in the 1960s. Aimed at promoting the new technology, the ISC was founded in Austria in 1972. The technology matured with each passing day after over 30 years of development. In recent years, in particular, China, with its greater economic development and scientific and technological progress, has been playing a leading role in the world in terms of both theoretical research and clinical application of cryotherapy. As an efficient medical method for treating tumors, cryotherapy has been adopted by more and more medical institutions in China and has achieved remarkable cancer-treating effectiveness."China: New Chair of the International Society of Cryosurgery (ISC)". 2015. - "Center for Devices and Radiological Health U.S. Food and Drug Administration".	2	15	4	0	0	0	0.266748	4	3,587
Fibrocystic breast changes \|Fibrocystic breast changes\| \|Other names\|\|Fibrocystic change, fibrocystic breast disease, fibrocystic breast condition\| \|Benign fibrous breast growths (highlighted in yellow).\| \|Symptoms\|\|Breast pain, breast cysts, breast masses\| \|Usual onset\|\|30 to 50 years old\| \|Risk factors\|\|Early age at first menstrual period, having children late or not having children\| \|Diagnostic method\|\|Periodic examination, possibly medical imaging or breast biopsy\| \|Differential diagnosis\|\|Breast cancer\| \|Treatment\|\|Education about the condition, a well fitting bra, pain medication\| \|Frequency\|\|Up to 60% of women\| Fibrocystic breast changes is a condition of the breasts where there may be pain, breast cysts, and breast masses. The breasts may be described as "lumpy" or "doughy". Symptoms may worsen during certain parts of the menstrual cycle due to hormonal stimulation. These are normal breast changes, not associated with cancer. Risk factors include an early age at first menstrual period and either having children at a late age or not at all. It is not a disease but represents normal breast changes. Diagnosis involves ruling out breast cancer. Fibrocystic changes include fibroadenomas, fibrosis, and papillomas of the breast. Management may involve education about the condition, using a well fitting bra, and pain medication, if needed. Occasionally danazol or tamoxifen may be used for pain. It is estimated that up to 60% of women are affected. Most commonly between the ages of 30 and 50 years. Signs and symptoms The changes in fibrocystic breast disease are characterised by the appearance of fibrous tissue and a lumpy, cobblestone texture in the breasts. These lumps are smooth with well defined edges, and free-moving regarding adjacent structures. These lumps can sometimes be obscured by irregularities in the breast associated with the condition. They're often found in the upper, outer sections of the breast (nearest to the armpit), but can be found throughout the breast. Women with fibrocystic changes may experience a persistent or intermittent aching or breast tenderness related to periodic swelling. Breasts and nipples may also be tender or itchy. Symptoms follow a periodic trend closely tied to the menstrual cycle. Symptoms tend to peak in the days to weeks before each period and decrease afterwards. At peak, breasts may feel full, heavy, swollen, and tender to the touch. No complications related to breastfeeding have been found. The exact mechanism of the condition is not fully understood, though it is known to be tied to hormone level fluctuation, the condition usually subsides after menopause and is closely related to the menstrual cycle. Post-menopausal under hormone replacement therapy have also reported symptoms of fibrocystic breast changes indicating hormones may play a major role. This condition is an accumulative process, partly caused by the normal hormonal variation during a woman's monthly cycle. The most important of these hormones include: estrogen, progesterone and prolactin. These hormones directly affect the breast tissue by causing cells to grow and multiply. Other hormones such as TSH, insulin, growth hormone and growth factors such as TGF-beta exert both direct and indirect effects by amplifying or regulating cell growth. Chronic hormonal fluctuations eventually produce small cysts and/or areas of dense or fibrotic tissue over the years. By the age of 30, multiple small cysts and breast pain may arise. Larger cysts usually do not occur until after the age of 35. Over time, presumably driven by aberrant growth signals, such lesions may accumulate epigenetic, genetic and karyotypic changes such as modified expression of hormone receptors and loss of heterozygosity. Several variants of fibrocystic breast changes may be distinguished and may vary in cause and genetic predisposition. Adenosis involves an abnormal count and density of lobular units, while other lesions appear to mainly arise from ductal epithelial origins. This is an exclusion diagnosis, mostly done based on the clinical presentation after ruling out breast cancer. Nipple fluid aspiration can be used as a classification cyst type method (and to some extent improve breast cancer risk prediction) but it's rarely used in practice. Biopsy or fine needle aspiration are rarely warranted. Fibrocystic breast disease is primarily diagnosed based on the symptoms, clinical breast exam and physical exam. During this examination, the doctor looks for unusual breast areas, both visually and manually. Also, the lymph nodes located in the axilla and lower neck are examined. A complete and accurate medical history is also helpful in the diagnosing process. If the patient's medical history and physical exam findings are consistent with normal breast changes, no additional tests are needed; otherwise the patient will be asked to return a few weeks later for reassessment. Women may detect lumps in their breasts during self-examination, if this happens it's strongly advised to visit a health professional right away. In order to establish whether the lump is a cyst or not, several imaging tests may be performed, these may include: mammography, X-rays, MRIs and ultrasound studies. Mammography is usually the first imaging test to be ordered when unusual breast changes are found during a clinical breast examination. A diagnostic mammography consists of X-ray series that provide clear and specific visualization areas in the breast. Ultrasounds and MRIs are commonly performed in conjunction with mammographies as they produce clear images of the breast that clearly distinguish between solid masses and fluid-filled breast cysts. These can better evaluate dense breast tissue; specially in young patients, under 30 years. Breast biopsy is a test used to confirm the suspected diagnosis, only after imaging tests have already been performed and revealed unusual looking areas. The procedure consists in removing a sample of breast tissue which is then studied by a pathologist under a microscope. The specialist analyzing the tissue sample will be able to conclude if the breast changes are benign or malignant. There are four main types of procedures for breast biopsy that may be performed, these include: fine-needle, core-needle, stereotactic biopsy and surgical approach. A fine-needle aspiration biopsy is usually ordered when the doctor is almost certain that the lump is a cyst. This test is generally performed in conjunction with an ultrasound which is helpful in guiding the needle into a small or hard to find lump. The procedure is painless and consists in inserting a thin needle into the breast tissue while the lump is palpated and seen live under sonographic ultrasound waves. The core-needle biopsy is normally performed under local anesthesia and in a physician's office. The needle used in this procedure is slightly larger than the one used in a fine-needle biopsy because the procedure is intended to remove a small cylinder of tissue that will be sent to the laboratory for further examination. A newer type of breast biopsy technique is the stereotactic biopsy which relies on a three-dimensional X-ray to guide the needle of non-palpable mass. The biopsy is performed in a similar manner, by using a needle to remove tissue sample but locating the specific area of the breast is done by X-raying the breast in two different angles. Surgical biopsy is performed to remove the entire lump or a part of it. It may be painful and is done under local anesthesia. Most women with fibrocystic changes who are asymptomatic do not need treatment, only a closer follow-up may be advised. There's no widely accepted treatment or prevention strategy for this condition. When the patient is symptomatic treatment may be necessary, same guidelines as treatment for cyclical breast pain are followed. There's still controversy whether benign breast conditions improve or worsen with the use of oral contraceptives or hormone replacement therapy. Small-scale studies have indicated that fibrocystic breast changes may improve by making dietary changes (especially by reducing caffeine intake and related methylxanthines found in chocolate or tea) and usage of vitamin supplements. Tentative evidence has shown beneficial effects of iodine supplementation in women with fibrocystic breast changes. There are usually no adverse side effects associated with this condition. In almost all cases it subsides after menopause. A possible complication arises through the fact that cancerous tumors may be more difficult to detect in women with fibrocystic changes. Breast cancer risk Breast cancer risk is elevated in a defined fraction of the lesions. Except for people with a strong family history of breast cancer, where the risk is two-fold, nonproliferative lesions have no increased risk. Proliferative lesions also have approximately a two-fold risk. In particular, atypical hyperplasia which is associated with an increased risk of developing breast cancer. There's two types of atypical hyperplasia: lobular and ductal; the lobular type is associated a greater cancer risk of approximately 5-fold and especially high relative risk in premenopausal women. Atypical ductal hyperplasia is associated with 2.4-fold risk. In contrast, a New England Journal of Medicine article states that for women with a strong familial history of breast cancer, the risk of future breast cancer is roughly doubled, independent of histological status. The article further states "The relative risk of breast cancer for the cohort was 1.56 (95 percent confidence interval, 1.45 to 1.68), and this increased risk persisted for at least 25 years after biopsy. The relative risk associated with atypia was 4.24 (95 percent confidence interval, 3.26 to 5.41), as compared with a relative risk of 1.88 (95 percent confidence interval, 1.66 to 2.12) for proliferative changes without atypia and of 1.27 (95 percent confidence interval, 1.15 to 1.41) for nonproliferative lesions. The strength of the family history of breast cancer, available for 4808 women, was a risk factor that was independent of histologic findings. No increased risk was found among women with no family history and nonproliferative findings. In the first 10 years after the initial biopsy, an excess of cancers occurred in the same breast, especially in women with atypia." It is not well understood whether the lesions are precursors of breast cancer or only an indication of increased risk, for most types of lesions the chance of developing breast cancer is nearly the same in the affected and unaffected breast (side) indicating only coincidence of risk factors. For atypical lobular hyperplasia there is high incidence of ipsilateral breast cancers indicating a possible direct carcinogenetic link. The estimated prevalence of fibrocystic breast changes in women over their lifetime vary widely in the literature, ranging from 30 to 60% over about 50 to 60% to about 60 to 75% of all women. The condition is most common among women between 30 and 50 years of age. In ICD-10 the condition is called diffuse cystic mastopathy, or, if there is epithelial proliferation, fibrosclerosis of breast. Other names for this condition include chronic cystic mastitis, fibrocystic mastopathy and mammary dysplasia. The condition has also been named after several people (see eponyms below). Since it is a very common disorder, some authors have argued that it should not be termed a "disease", whereas others feel that it meets the criteria for a disease. It is not a classic form of mastitis (breast inflammation). This entity has historically also been termed Bloodgood’s disease, Cooper's disease (after Sir Astley Paston Cooper, 1st baronet), Phocas' disease, Reclus’ disease and Reclus’ syndrome (after Paul Reclus), Reclus-Schimmelbusch disease, Schimmelbusch disease and Tillaux-Phocas disease. - Ferri, Fred F. (2018). Ferri's Clinical Advisor 2019: 5 Books in 1. Elsevier Health Sciences. p. 548. ISBN 9780323550765. - "Breast Masses (Breast Lumps)". Merck Manuals Professional Edition. Retrieved 3 November 2018. - Santen, RJ; Mansel, R (21 July 2005). "Benign breast disorders". The New England Journal of Medicine. 353 (3): 275–85. doi:10.1056/NEJMra035692. PMID 16034013. - "Fibrocystic Breast Condition".2010/04/13, MedicineNet.com - "Fibrocystic Breast Condition". Archived from the original on 2010-02-18. Retrieved 2010-04-13.2010/04/13 - Cann, Stephen A.; van Netten, Johannes P.; van Netten, Christiaan (2000). "Hypothesis: iodine, selenium and the development of breast cancer". Cancer Causes and Control (review). 11 (2): 121–127. doi:10.1023/A:1008925301459. ISSN 0957-5243. PMID 10710195. S2CID 2665461. - Joseph E. Pizzorno; Michael T. Murray (14 September 2012). Textbook of Natural Medicine. Elsevier Health Sciences. p. 1371. ISBN 978-1-4377-2333-5. - Venturi, S. (2001). "Is there a role for iodine in breast diseases?". The Breast. 10 (5): 379–382. doi:10.1054/brst.2000.0267. PMID 14965610. - Aceves, C.; Anguiano, B.; Delgado, G. (2005). "Is iodine a gatekeeper of the integrity of the mammary gland?". Journal of Mammary Gland Biology and Neoplasia. 10 (2): 189–196. doi:10.1007/s10911-005-5401-5. PMID 16025225. S2CID 16838840. - Vaidyanathan, L.; Barnard, K.; Elnicki, D M. (May 2002). "Benign Breast Disease: When To Treat, When To Reassure, When To Refer". Cleveland Clinic Journal of Medicine. 69 (5): 424–439. doi:10.3949/ccjm.69.5.425. PMID 12022387. - "Tests and diagnosis". Archived from the original on 2010-03-22.2010/04/13 - "Types of non-cancerous breast conditions".2010/04/13 - Gadducci A, Guerrieri ME, Genazzani AR (February 2012). "Benign breast diseases, contraception and hormone replacement therapy". Minerva Ginecologica. 64 (1): 67–74. PMID 22334232. - Ethel Sloane, Biology of Women, Cengage Learning, 2002, p. 200-201 - "Iodine: Fact Sheet for Health Professionals". NIH. Retrieved 2015-02-07. - Kessler JH (2004). "The effect of supraphysiologic levels of iodine on patients with cyclic mastalgia". The Breast Journal (Randomized Controlled Trial). 10 (4): 328–36. doi:10.1111/j.1075-122X.2004.21341.x. PMID 15239792. S2CID 2685253. - Ethel Sloane, Biology of Women, Cengage Learning, 2002, p. 200 - Marshall, LM; Hunter, DJ; Connolly, JL; Schnitt, SJ; Byrne, C; London, SJ; Colditz, GA (1997). "Risk of breast cancer associated with atypical hyperplasia of lobular and ductal types". Cancer Epidemiology, Biomarkers & Prevention. 6 (5): 297–301. PMID 9149887. - Hartmann, L. C.; Sellers, T. A.; Frost, M. H.; Lingle, W. L.; Degnim, A. C.; Ghosh, K; Vierkant, R. A.; Maloney, S. D.; Pankratz, V. S.; Hillman, D. W.; Suman, V. J.; Johnson, J; Blake, C; Tlsty, T; Vachon, C. M.; Melton Lj, 3rd; Visscher, D. W. (2005). "Benign breast disease and the risk of breast cancer". New England Journal of Medicine. 353 (3): 229–37. doi:10.1056/NEJMoa044383. PMID 16034008. - Page, D. L.; Schuyler, P. A.; Dupont, W. D.; Jensen, R. A.; Plummer Jr, W. D.; Simpson, J. F. (2003). "Atypical lobular hyperplasia as a unilateral predictor of breast cancer risk: a retrospective cohort study". The Lancet. 361 (9352): 125–9. doi:10.1016/S0140-6736(03)12230-1. PMID 12531579. S2CID 6429291. - Susan L. Norwoord (March 1990). "Fibrocystic Breast Disease An Update and Review". Journal of Obstetric, Gynecologic, & Neonatal Nursing. 19 (2): 116–121. doi:10.1111/j.1552-6909.1990.tb01629.x. PMID 2181087. - Kelly A. McGarry; Iris L. Tong (6 July 2012). The 5-Minute Consult Clinical Companion to Women's Health. Lippincott Williams & Wilkins. p. 86. ISBN 978-1-4511-1654-0. - Roger P. Smith (1 December 2008). Netter's Obstetrics and Gynecology. Elsevier Health Sciences. p. 371. ISBN 978-1-4377-2137-9. - Disorders of breast (N60-N64) in ICD-10. - Atlantic Women’s Specialists. "Fibrocystic Breast Changes". Archived from the original on 29 January 2013. Retrieved 21 June 2012. - Santen RJ, Mansel R (July 2005). "Benign breast disorders". N. Engl. J. Med. 353 (3): 275–85. doi:10.1056/NEJMra035692. PMID 16034013. - Gokhale, Sudheer (August 2009). "Ultrasound Characterization of Breast Masses". Indian Journal of Radiology and Imaging. 19 (3): 242–247. doi:10.4103/0971-3026.54878. PMC 2766883. PMID 19881096. - synd/1891 at Who Named It?	2	18	3	0	1	2	0.785001	6	4,025
Set a Pace for Better Implantable Defibrillator Coding Revitalize your coding expertise with the latest in fibrillation advancements. Defibrillators help to prevent sudden death secondary to life threatening arrhythmias. They may provide a low-level shock or cardioversion for ventricular tachycardia, or a high level shock for ventricular fibrillation. Procedural Approaches and Techniques The system consists of a generator placed in the subcutaneous tissues, and one or more leads. A right ventricular (RV) defibrillating lead is placed to provide electrical shocks. A right atrial (RA) lead may be inserted to allow for dual pacing. A left ventricular (LV) lead may be placed in the coronary sinus for cardiac resynchronization therapy (CRT or biventricular pacing) in patients with heart failure. Leads usually are placed via a transvenous technique, but they may be implanted into the epicardium (on the outside of heart) during an open or endoscopic approach. Recently, subcutaneous defibrillators have been introduced with a lead placed in the subcutaneous tissues. This obviates the need for transvenous or epicardial leads. The advantage is ease of placement, and fewer potential complications related to venous stenosis secondary to the lead, and/or infected leads within the heart. The subcutaneous system does not allow pacing as in a traditional transvenous system. After insertion of a defibrillator, defibrillation threshold testing often is performed. The patient is sedated and placed into fibrillation to check the function of the implanted device. The battery in the generator must be replaced over time. The CPT® codes to describe such replacement procedures (see the sidebar “Implanted Cardiac Device Codes” for code descriptions) include insertion of the new generator and removal of the existing generator. The leads are checked during the generator change. Leads may become displaced (which requires repositioning) or may be damaged or faulty (which requires repair or replacement with a new lead). When an existing lead is not useable, it may be left in place and capped, or removed. Removal can be difficult and may require the use of laser energy. Fluoroscopy is used in these cases, but is included in CPT® codes 33206-33249, 33262-33264, and 33270-33273. Here’s a general run-down of associated procedures and applicable codes. A complete code list with descriptions is at the end of this article. - 33249 describes insertion of a defibrillator, including the transvenous RV defibrillating lead +/- atrial lead. - 33202 and 33203 describe open or endoscopic (respectively) insertion of epicardial leads. - 33215 reports repositioning of an RA or RV lead. Insertion of a single transvenous new lead is reported with 33216; and for two new leads, report 33217. - 33218 describes repair of a single existing lead; for repair of two leads, report 33220. - 33223 describes relocation of a skin pocket. It is not used for revision of an existing pocket to accommodate a new generator. - 33224 reports adding a LV lead for biventricular pacing to an existing system. Turn to 33225 when the physician adds an LV lead at the time of a new generator placement. Report repositioning of an LV lead with 33226. - 33240 (single lead system), 33230 (dual lead), or 33231 (biventricular system with RV and LV leads +/-RA lead) describes insertion of a generator and connection to lead(s) already in place. - 33241 describes removal of an existing generator (i.e., for infection). Report removal and replacement of a generator (e.g., battery is nearly depleted) for elective replacement indicator (ERI) with either 33262 (single lead generator), 33263 (dual lead), or 33264 (biventricular defibrillator with RV, LV and +/-RA leads). - 33243 reports removal of defibrillator lead(s) by open thoracotomy; report 33244 for transvenous extraction. - 93641 reports defibrillation threshold (DFT) testing at the time of placement or replacement of a generator. If DFT is performed at a later date (i.e., secondary to atrial thrombus), report 93642. - 33249 reports a new RA and/or RV lead are placed at the time of a new generator placement for ERI. Do not report a replacement generator code plus new lead insertion code. In this scenario, also report 33241 for removal of the existing depleted generator. - 33270 reports placement of a subcutaneous defibrillator system, which includes the generator, subcutaneous lead, and DFT testing, if performed. - 33271 describes insertion of a subcutaneous lead at a later date; report 33272 for removal and 33273 for repositioning. Report DFT testing performed at a different date of service for a subcutaneous defibrillator with 93644. A Perfect Example A 64-year-old male has a documented cardiac arrest due to ventricular fibrillation. Antibiotics are given and venography is performed to help guide venous access. A subclavicular pocket is created. The subclavian vein is accessed and three wires are placed. A defibrillating lead is placed into the RV. Next, a pacing lead is placed into the RA. Finally, the coronary sinus is cannulated and an LV lead is placed into the coronary sinus. The generator is brought to the field where the three leads are connected to the generator. The patient is sedated and DFT testing is performed and found to be adequate. The incision is closed in layers. CPT® codes for this case include 33249-Q0 (insertion of RV and RA leads and generator), 33225 (LV lead), and 93641 (DFT testing). Do not code for routine venography during defibrillator placement. Fluoroscopy is included in the insertion. The defibrillator was placed for ventricular fibrillation: ICD-10-CM I49.01 Ventricular fibrillation. The implantation was for secondary prevention of sudden death, which is covered per the Medicare National Coverage Determination. The patient’s data does not have to be submitted to the registry for coverage, and modifier Q0 is not necessary. If the data is submitted to the registry, modifier Q0 can be appended but is optional (see companion article “Establish Medical Necessity for Implantable Cardioverter-defibrillators” ). 33202 Insertion of epicardial electrode(s); open incision (eg, thoracotomy, median sternotomy, subxiphoid approach) 33203 endoscopic approach (eg, thoracoscopy, pericardioscopy) 33215 Repositioning of previously implanted transvenous pacemaker or implantable defibrillator (right atrial or right ventricular) electrode 33216 Insertion of a single transvenous electrode, permanent pacemaker or implantable defibrillator 33217 Insertion of 2 transvenous electrodes, permanent pacemaker or implantable defibrillator. 33218 Repair of single transvenous electrode, permanent pacemaker or implantable defibrillator 33220 Repair of 2 transvenous electrodes for permanent pacemaker or implantable defibrillator. 33223 Relocation of skin pocket for implantable defibrillator 33224 Insertion of pacing electrode, cardiac venous system, for left ventricular pacing, with attachment to previously placed pacemaker or implantable defibrillator pulse generator (including revision of pocket, removal, insertion, and/or replacement of existing generator) +33225 Insertion of pacing electrode, cardiac venous system, for left ventricular pacing, at time of insertion of implantable defibrillator or pacemaker pulse generator (eg, for upgrade to dual chamber system) (List separately in addition to code for primary procedure) 33226 Repositioning of previously implanted cardiac venous system (left ventricular) electrode (including removal, insertion and/or replacement of existing generator). 33230 Insertion of implantable defibrillator pulse generator only; with existing dual leads 33231 with existing multiple leads 33240 with existing single lead 33241 Removal of implantable defibrillator pulse generator only 33243 Removal of single or dual chamber implantable defibrillator electrode(s); by thoracotomy 33244 by transvenous extraction 33249 Insertion or replacement of permanent implantable defibrillator system, with transvenous lead(s), single or dual chamber 33262 Removal of implantable defibrillator pulse generator with replacement of implantable defibrillator pulse generator; single lead system 33263 Removal of implantable defibrillator pulse generator with replacement of implantable defibrillator pulse generator; dual lead system 33264 Removal of implantable defibrillator pulse generator with replacement of implantable defibrillator pulse generator; multiple lead system 33270 Insertion or replacement of permanent subcutaneous implantable defibrillator system, with subcutaneous electrode, including defibrillation threshold evaluation, induction of arrhythmia, evaluation of sensing for arrhythmia termination, and programming or reprogramming of sensing or therapeutic parameters, when performed 33271 Insertion of subcutaneous implantable defibrillator electrode 33272 Removal of subcutaneous implantable defibrillator electrode 33273 Repositioning of previously implanted subcutaneous implantable defibrillator electrode 93641 Electrophysiologic evaluation of single or dual chamber pacing cardioverter-defibrillator leads including defibrillation threshold evaluation (induction of arrhythmia, evaluation of sensing and pacing for arrhythmia termination) at time of initial implantation or replacement; with testing of single or dual chamber pacing cardioverter-defibrillator pulse generator 93642 Electrophysiologic evaluation of single or dual chamber transvenous pacing cardioverter-defibrillator (includes defibrillation threshold evaluation, induction of arrhythmia, evaluation of sensing and pacing for arrhythmia termination, and programming or reprogramming of sensing or therapeutic parameters) 93644 Electrophysiologic evaluation of subcutaneous implantable defibrillator (includes defibrillation threshold evaluation, induction of arrhythmia, evaluation of sensing for arrhythmia termination, and programming or reprogramming of sensing or therapeutic parameters) Occasionally, there are recalls for defibrillator leads and generators. The hospital may receive a replacement device at no cost or at a reduced cost. When a credit for the replaced device is 50 percent or greater than the cost of the device, hospitals must report the amount of the credit in the amount field for value code “FD” (credit received from the manufacturer for a replaced medical device) on the UB-04 claim form. David Dunn, MD, FACS, CIRCC, COC, CCVTC, CCC, CCS, RCC, vice president of ZHealth Publishing, oversees physician coding. He coauthors the Vascular & Endovascular Surgery Coding Reference and the new Cardiothoracic Surgery Coding Reference from Dr. Z’s Medical Coding Series, and is a contributor to the Interventional Radiology Coding Reference and the Diagnostic & Interventional Cardiovascular Coding Reference. Dunn served as president of the AAPC National Advisory Board from 2013-2015, and is a member of the Nashville, Tenn., local chapter. Latest posts by David Dunn (see all) - Set a Pace for Better Implantable Defibrillator Coding - August 1, 2016 - Catheter Placement is Critical to Coding Arterial System Procedures - February 25, 2010	4	32	28	0	0	2	0.592463	30	2,549
Home > Flashcards > Print Preview The flashcards below were created by user on FreezingBlue Flashcards . What would you like to do? What is the order of air going through the respiratory tract? - 1. Nasopharynx - 2. Pharynx - 3. Epiglottis - 4. Larynx - 5. Vocal cords - 6. Trachea - 7. CARINA - 8. Main Stem Bronchus - 9. Bronchi - 10. Bronchiole - 11. Respiratory Bronchioles - 12. Alveolar Ducts - 13. Alveolar Sacs What makes up the upper respiratory tract? What makes up the lower respiratory tract? - Primary bronchi What covers the lungs? - 2 layers of pleura - Visceral (inside) - Parietal (outside) What is between the two layers of pleura? - Potential space - Allows lungs to expand What is generated by the intercostals muscles and diaphragm constriction? - Negative pressure - Makes body suck in air What is the role of the epiglottis? During swallowing, prevents food from going into the trachea and instead directs it to the esophagus, which is posterior. What is the role of the sinuses? - 1. Heat and humidify air - 2. Resonate voice - 3. Lighten weight on skull - 4. Cushioning effect when blow to the face What are the different types of sinuses? - Frontal sinus - Ethmoid sinus - Maxillary sinus Where is the frontal sinus located? Above the eyes Where is the ethmoid sinus located? Sides of the nose Where is the maxillary sinus located? Under the eyes Where are the sinuses located? What is special about the structure? - Within the upper respiratory tract - Paired structures Where does gas exchange occur in the respiratory system? What is the function of the vocal cords? They vibrate, modulating the flow of air being expelled from the lungs during phonation What makes up the basement membrane of an alveolar sac? - 2 cells are required for exchange of gas at the alveolar membrane: The Alveolar Type 1 Cells and the Capillary Endothelial Cells - Type 2 alveolar cells produce surfactant and are NOT involved in the passive diffusion of oxygen and carbon dioxide Where are Type 1 cells found in the respiratory system? What is the function of Type 1 cells? Diffusion of oxygen and carbon dioxide Where are Type 2 cells found in the respiratory system? In the lungs What is the function of Type 2 cells? - Produce surfactant - Reduces the surface tension of the moisture that covers the alveolar walls - No role in diffusion In what structure are the bronchiole pharmacologic receptors located? Smooth muscle surrounding the bronchiole tubes What is the innervation of the bronchiole pharmacologic receptors and their functions? - Sympathetic (beta 2 receptors): dilate - Parasympathetic (M3 cholinergic): constrict What is one respiratory cycle? One breath in, one breath out What does I to E ratio mean? Time breathing in versus time breathing out What is the normal I to E ratio? What I to E ratio is present in asthma? What I to E ratio is present in hypoventilation? What is RR? - Respiratory rate - The number of breathing cycles per minute What is the normal RR? How does RR vary by age? - Faster as infant, young child - By about age 16, to normal range Take a breath in and blow it out The movement of air in and out of the lungs - Transfer gases through the cell membrane - Move oxygen into cells and carbon dioxide out of cells Carry oxygen through the body (via hemoglobin) How does Alveolar pressure differ from Atmospheric pressure during inhalation? Inhalation: Expansion of the thoracic cage reduces alveolar pressure below atmospheric pressure, so air moves into the lungs How does Alveolar pressure differ from Atmospheric pressure during exhalation? Due to elastic recoil in a normal state, the Palv will > Patmospheric. Exhalation that requires forced skeletal muscle contraction occurs when forcing a breath out such as using a peak flow meter, blowing up a balloon, performing an FEV1, or during an asthma attack. Here Palv also is > Patmospheric , so there is air flow out. What is transpleural pressure (Pip)? Pip (transpleural pressure) = pressure between the pleural and outside chest What must occur to generate a negative Pip? - Diaphragm and inspiratory intercostals contract - Thorax expands Define dead space. Air not contacting an alveolar sac Define tidal volume. - Amount of air moved in the airways in a single breath Define residual volume. - How much air is left over in the lungs following maximal exhalation Define vital capacity. How much air goes in/out in a maximal force breath Define total lung capacity. - Total amount of air the lung can accommodate - VC + RV - Amount of air that is forcibly exhaled in one second - Should be a majority of the air What is minute ventilation? How much air flows or is exchanged in one minute What is the difference between Minute ventilation and Alveolar ventilation? - Alveolar ventilation= minute ventilation – dead-space ventilation - Alveolar ventilation is how much air actually makes to the alveolus Describe pulmonary compliance. A measure of the lung’s “stretchability” What occurs if pulmonary compliance is abnormally high? - The lungs might fail to hold themselves open - Prone to collapse What occurs if pulmonary compliance is abnormally low? The work of breathing is increased What is surfactant? A compound that lowers the surface tension of a liquid What is the function of a surfactant in the lungs? - Lowers hydrostatic pressure/surface tension - Increases lung compliance - Makes lungs easier to expand - Allows alveoli’s to stay open What happens to the amount of surfactant secretion during a deep breath? When is the production of surfactant done in fetal lungs? - Late in gestation - Neonatal infants cannot produce surfactant, leading to respiratory distress Where in the alveolar sac is surfactant found? Lining the type 1 cells, in the inner surface of the alveolus What is pulmonary surfactant made of? Phospholipids and protein Describe the diffusion direction and pressure changes found at the alveolar / capillary membrane and at the tissue / capillary membrane. - Diffusion of oxygen into (toward the blood) the cells - Outward (toward the alveolar air) diffusion of carbon dioxide - Pressure change from higher to lower after diffusion What is the main form of oxygen in systemic arterial blood? Bound to hemoglobin What is the main form of carbon dioxide in systemic arterial blood? As bicarbonate HCO3- (ionic form of CO2) How might oxygen and carbon dioxide concentrations be affected during hyperventilation? - Increasing respiratory efforts and increasing minute ventilation - Breathing off lots of CO2 so the equation pushes right and as a result H+ ion decreases and thus blood pH increases How might their concentrations be affected during hypoventilation? - SLOWING down your respiratory efforts so the Minute Ventilation is decreased - Arterial P CO2 will rise and thus push the carbonic anhydrase equation to the left - Causing an increase in H+ ion concentration and lowering blood pH What is the carbonic anhydrase equation? H+ + HCO3- = H2CO3 = H20 + CO2 What is narcosis? Coma due to carbon dioxide intake What is asphyxiation? Death by lack of oxygen What is the oxygen content in air? What is the oxygen content when administering CPR? Is this enough to sustain life? Describe the basic structure of hemoglobin. - Contains 4 protein subunits (called globins) - 2 Alpha subunits, 2 Beta subunits - Each subunit has one Heme group Where does oxygen bind to hemoglobin? Each Heme group binds one O2 molecule at the Fe++ atom How many molecules of oxygen bind 1 heme group and 1 Hb molecule? - Heme: one O2 molecule - Hb: four O2 molecules Explain the Oxygen – Hb dissociation curve? As the concentration of oxygen increases, the percentage of hemoglobin saturated with bound oxygen increases until all of the oxygen-binding sites are occupied (100% saturation) What is the abbreviation for oxygenated hemoglobin? What is the abbreviation for deoxygenated hemoglobin? How does the presence of hemoglobin affect oxygen diffusion at the alveolar / capillary membrane? Hemoglobin binds the O2, and thus makes more O2 diffuse to the blood because the gradient is still lower in the blood (unbound O2) What are the five measurements in a blood gas analysis? - 1. Arterial blood pH - 2. Partial pressure of oxygen - 3. Partial pressure of carbon dioxide - 4. Oxygen saturation - 5. Bicarbonate What is the abbreviation for the partial pressure of oxygen? What is the abbreviation for the partial pressure of carbon dioxide? What is the abbreviation for oxygen saturation? What is the abbreviation for bicarbonate? What is acidosis? Blood pH is less than 7.35 What is alkalosis? Blood pH is greater than 7.45 What is hypoxemia? PaO2 is less than 70mmHg What is hypercarbia? PaCO2 is greater than 60mmHg What is hypocarbia? PaCO2 less than 30mmHg What is desaturation? Hb-O2 is less than 90% What is the difference between arterial and venous blood with respect to PCO2, PO2 & Oxygen Saturation? - Arterial blood: PaCO2= 40mmHg PaO2=100mmHg Oxygen saturation=near 100% - Venous blood: PaCO2= 46mmHg PaO2=40mmHg Oxygen saturation less than 75% What is a noninvasive modality to measure oxygenation and how does it work? - Pulse oximetry machine - Calculates the Hb-O2 amount by sensing its wavelength - Different wavelengths of Hb-O2 and Hb What are the three chemosensory controls of respiration? Arterial oxygen pressure (P O2), arterial carbon dioxide pressure (P CO2) and blood pH Where are their chemosensory controls of respiration receptors located? Aortic and carotid bodies sense changes in these 3 chemical parameters and send that afferent information to the DRG / VRG respiratory control center located in the medulla oblongata. The Pons has more respiratory control from inputs from the cerebral cortex (such as fright, excitement, muscle movement) What cranial nerves function as their afferents regarding the chemosensory controls of respiration? CN9 and CN10 Where in the CNS is the respiratory control center located? - In the brainstem - Medulla: input for chemosensory afferent input and efferent output to diaphragm and intercostals muscles - Pons: regulatory role in I/E transitions What are Kussmaul Respirations? Deep hyperventilation to blow off CO2 What is the clinical finding associated with Kussmaul Respirations? How does rising PCO2 affect blood pH? As PaCO2 rises, pH blood lowers What are the ABCs of resuscitation? Describe the appropriate position of the head for assuring an open airway in an unconscious individual. - “Sniffing Position” - Neck neutral and chip up; mandible moved forward What is cyanosis? Bluing of the skin Under what physiologic conditions will cyanosis be visible? When 1/3 of Hb is present as Deoxy-Hb What are the four vital signs? What are three types of oxygen delivery systems for a breathing patient? - Nasal cannula - Face mask How much additional oxygen can be provided in each oxygen delivery system? - Nasal Cannula: 7% - Face Mask: 19% - Mask/Reservoir: 39% What is the risk of ventilating an 80kg adult with a pediatric ambu bag? Will only ventilate dead space, no ventilation actually exchanging in the alveoli What is the risk of ventilating a 3kg neonate with an adult ambu bag? Pop lungs, way too much air for the neonates lungs What are the two means to deliver positive pressure ventilation? - Bag/mask ventilation - Intubation and ventilator What is intubation? - The placement of a tube inserted into the trachea - Serves as an open passage through the upper airway - Permits air to pass freely to and from the lungs in order to ventilate the lungs - Can be connected to ventilator machines to provide artificial respiration Where is the proper anatomic location for placing an ETT (endotracheal tube)? - Below clavicles - Above carina Describe a hospital “code”. - Full cardiopulmonary arrest or rapid decline in vital signs - Patient needs immediate stabilization to prevent death What would be the pharmacist’s role in a “code”? - Drawing up meds (epinephrine) - Making sure correct dose What are the standard resuscitation drugs that can be delivered via an ETT? - Inhaled (anesthetics, steroids) Describe a pneumothorax. What are its major physiologic complications? - Partial or complete collapse of a lung due to filling the thorax with air between the visceral and parietal pleura - Elevates intrathoracic pressures leading to impaired lung ventilation and impaired lung perfusion What are the major physiologic complications of pneumothorax? - Rapidly alter respiratory dynamics - Elevated pressure leads to severe hypoxemia and death due to inadequate ventilation, oxygenation, venous return to heart What are the major considerations for placement of an ETT? - General anesthesia What types of medications are utilized in a rapid sequence intubation? - 1. Sedative/hypnotic - 2. Skeletal muscle paralytic - 3. Atropine/lidocaine What are the mechanisms in asthma that lead to decreased caliber of bronchial lumen? - 1. External smooth muscle contraction (broncho-constriction) - 2. External bronchial wall edema - 3. Intra-lumical inflammation and mucous plugging What pharmacologic receptors are involved in the mechanisms of asthma? - 1. Sympathetic (Beta2): dilation - 2. Parasympathetic (Cholinergic): constriction What inflammatory mediators are involved in the mechanisms of asthma? Use of corticosteroids, antihistamines, leukotriene inhibitors What role does a mast cell have in the inflammatory response? Responsible for synthesizing mediators of inflammation What is the effect of sympathetic receptors regarding asthma? What is the effect of parasympathetic receptors regarding asthma? What is the value of using FEV1 and PEF measurements in the diagnosis and management of asthma? - Can help a patient decide if there is a need for medication or doctor’s visit - Especially a quick acting bronchodialator Why is asthma primarily an expiratory problem? Because bronchial lumen is already narrowed, greater intrathoracic pressure is needed to exhale air (more positive pressure) Name common triggers of asthma? - EVERYTHING can trigger! - Acute respiratory infections - Weather changes - Air quality - Inhalant irritants What is an asthma care plan? Helps patients decide whether their breathing is good, or needs medication, or needs medical attention What types of medications could be utilized in an asthma care plan? - Routine control medications in green zone - In yellow/red zone, use of fast acting bronchodilators (Maxair/Albuterol) Calculate pack years of a person smoking one pack per day for 10 years. 10 pack years What is the risk of lung cancer, regarding pack years? Over 20, significant increase in cancer What are other non-cigarette exposure risks for lung cancer? How does smoking affect the non-cigarette exposure risks for lung cancer? What is the different between metastatic and primary lung cancer? - Metastatic: started in another organ; breast, colon, prostate - Primary lung cancer: started in lung (airway tumors usually present) What are the cellular origins of lung cancer? - Neuro/endocrine origin - Epithelial origin - Pleural origin Describe physiologic consequences of a pulmonary tumor. - Hemoptysis (coughing up blood) - Shortness of breath - Weight loss Why is lung cancer so fatal? - Obstruct larger and small airways - Restrict lung expansion - Induce lung collapse - Hemorrhage into airways - Reduce effective surface area for diffusion - Fluid/blood accumulation in pleural space What is influenza? Viral infection of the respiratory tract What is sinusitis? Bacterial infection of the sinuses What is bronchitis? Bacterial/viral infection of the bronchi What is pneumonia? Bacterial/viral infection of the lungs How do pharmacologic treatments vary with respect to viral and bacterial etiologies of common respiratory infections? - Viral: fluids, rest - Bacterial: antibiotics Why not give antibiotics to everyone with a respiratory infection? - Drug resistance - Unwanted side effects - Kill of natural flora - Allergies great in antibiotics What are the five major functions of the kidney? - 1. Regulation of water, inorganic ion balance, and acid-base balance - 2. Removal of metabolic waste products from the blood - 3. Removal of foreign chemicals from the blood - 4. Gluconeogenesis - 5. Production of hormones/enzymes (erythropoietin, Renin, Vitamin D) What are the three basic processes in the kidney that determine what is excreted from the body and what stays? - 1. Filtration - 2. Secretion - 3. Reabsorption Describe glomerular filtration. Movement of fluid and solutes from the glomerular capillaries into Bowman’s space What cannot be filtered through glomerular filtration? Why? - Proteins and protein-bound substances - Cannot be filtered due to the small pore size and negative charge of the membrane (repels proteins) Describe tubular secretion. - Transport or diffusion of solutes from the peritubular capillaries into the tubules - Addition of solutes into fluid - Waste products, when filtration didn’t get rid of enough Describe tubular reabsorption. - Transport or diffusion of materials from the filtrate into the tubules - Materials that the body wants to keep Describe a substance that is filtered and secreted but not reabsorbed. - Plasma that enters nephron is completely cleared of the substance - Examples: toxins, metabolic wastes Describe a substance that is filtered and partially reabsorbed. - A certain fraction is excreted, sometimes subject to physiological control - Examples: inorganic ions (sodium, potassium, calcium) Describe a substance that is filtered and completely reabsorbed. - Kidney has no effect on levels of these substances - Examples: glucose, other nutrients In what locations can nephrons be? Describe each. - Juxtamedullary—near the border with medulla, loops of Henle go deep into medulla - Cortical—corpuscle and most of loop in cortex What is the importance of a juxtamedullary location? - Only 15% - Important function in generating osmotic gradient What is the equation for the amount of something excreted by the kidneys? Amount excreted = amount filtered + amount secreted – amount reabsorbed What allows the formation of glomerular filtrate in Bowman’s capsule? Sum of opposing pressures: hydrostatic pressure from the heart favors filtration, osmotic and hydrostatic pressure of the filtrate oppose it What is the normal rate of filtration? How can filtration rate be adjusted? Changing the radius of the arterioles How can you decrease GFR? - Constrict afferent arterioles - Dilate efferent arterioles How can you increase GFR? - Dilate afferent arterioles - Constrict efferent arterioles What structures make up the filter of the kidneys? Glomerulus (capillary endothelium, basement membrane, podocyte foot processes) What is in filtrate? - Urea, wastes - Inorganic ions What is excluded in the filtrate? - Nutrients that are needed by the body What is clearance of the kidneys? Amount of plasma from which a substance is completely removed What is the normal clearance of glucose? 0, all is reabsorbed How is glucose clearance different in diabetics? Why? - Reabsorption is finite, maximum can be reached - Plasma glucose concentration saturates transporters, with excess glucose remaining in the tubules How can clearance of creatinine or inulin be used to measure GFR? - Completely or almost completely cleared - Clearance equal to GFR How can clearance be used to determine whether a substance is secreted or reabsorbed? - If a substance has a clearance greater than GFR, secreted - If clearance is less than GFR, reabsorbed How does the bladder filling reflex work? - PSNS inhibited, detrusor muscle relaxed - SNS input keeps internal sphincter contracted (closed) - Somatic motor input keeps external sphincter closed How does the micturition reflex work? - 1. Afferents detect stretch of bladder wall - 2. PSNS activated, detrusor muscle contracts - 3. SNS inhibited, opens internal sphincter - 4. Somatic motor input can be voluntarily inhibited to allow urine release Can the output of water, salt, etc., change? Why? - Extreme sweating, diarrhea, salty meals What would you like to do? Home > Flashcards > Print Preview	2	6	0	0	0	1	0.373267	1	5,071
ICD-10 Chapter V: Mental and behavioral disorders is part of the International Classification of Diseases produced by the World Health Organization (WHO). Mental health professionals have long relied on a coding system known as DSM-IV. In the DSM-IV system Psychiatric Diagnoses are categorized by the Diagnostic and Statistical Manual of Mental Disorders, 4th.edition. The manual is published by the American Psychiatric Association and covers all mental health disorders for children and adults. It also lists known causes of these disorders, statistics in terms of gender, age at onset, and prognosis as well as some research concerning the optimal treatment approaches. The coding system used in the DSM-IV is designed to correspond with the codes used in the ICD-10 classification, although not all codes may match at all times because the two publications are not revised synchronously. ICD-10 and DSM-IV diagnoses are comparable for the most relevant points. The ICD-10-CM diagnosis classification is used to code patient diagnosis with date of service October 1, 2013 and after. Each chapter of ICD-10 begins with a listing of related code ranges (blocks). Chapter 5 ICD-10 Blocks include: - F01-F09 Mental disorders due to known physiological conditions; - F10-F19 Mental and behavioral disorders due to psychoactive substance use; - F20-F29 Schizophrenia, schizotypal and delusional, and other non-mood psychotic disorders; - F30-F39 Mood [affective] disorders; - F40-F48 Anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders; - F50-F59 Behavioral syndromes associated with physiological disturbances and physical factors; - F60-F69 Disorders of adult personality and behavior; F70-F79 Mental retardation; - F80-F89 Pervasive and specific developmental disorders; - F90-F98 Behavioral and emotional disorders with onset usually occurring in childhood and adolescence; and, - F99 Unspecified mental disorder. As you can see, each block begins with the same alpha letter “F”. There is no requirement for a 7th character extensor in chapter 5. A number of codes have been significantly expanded in ICD-10 A number of codes have been significantly expanded in ICD-10 (e.g., injuries, diabetes, substance abuse, postoperative complications). F10.182 – “Alcohol abuse with alcohol-induced sleep disorder” is an example of this expansion. The block that covers schizophrenia, schizotypal states and delusional disorders (F20-F29) has been expanded by the introduction of new categories such as undifferentiated schizophrenia (F20.3), schizoaffective disorder, depressive type (F25.1), and schizotypal disorder (F21). Alcohol dependence is defined in the I-10 classification in a way that is similar to the DSM. Category F10.1- F10.99 describes alcohol abuse and dependence. These categories require 5 or 6 characters to complete the code. There is no referencing back for a 5th digit (ICD-9 requirement), each code is complete. Example: code F10.221 “Alcohol dependence with intoxication delirium.” Bipolar disorder, category F31, includes manic-depressive illness, manic-depressive psychosis, and manic-depressive reaction. Example: code F31.62 states “Bipolar disorder, current episode mixed, moderate.” Clinical documentation will require greater detail than physicians have been using for the past 30 years. Training of both coders and providers will take time and should be factored into the ICD-10 transition budget for years 2012-2013. October 1, 2013, is the deadline for implementation and use of ICD-10-CM and ICD-10-PCS. For diagnosis coding purposes, the ICD-10 diagnosis codes will be used to assign codes to documented conditions for a specific patient encounter, in any place of service. If you are assigning ICD-9 codes now, you will be assigning ICD-10 diagnosis codes on October 1, 2013. CPT and HCPCS codes will not change for physician billing. It is recommended that clinicians should follow the general rule of recording as many diagnoses as are necessary to cover the clinical picture. You may be assigning codes from other chapters in ICD-10-CM It is very likely you will be assigning codes from other chapters in ICD-10-CM based on medical record documentation. Chapter 19 contains codes for injuries, poisoning, and adverse effects. Codes from chapter 19 (T40, T51) for example, would be used in conjunction with the F10-F19 codes if a patient has an acute alcohol or drug poisoning, even if the patient is dependent on alcohol or drugs. Another example involves a code from the nervous system (G30.9). If the patient has documented dementia due to an underlying condition, the underlying condition (eg, alzheimer’s), is first-listed code (G30.9). The dementia would be second-listed (F02.81). Chapter 5, Block F01-F09, comprises a range of mental disorders grouped together on the basis of their having in common a demonstrable etiology in cerebral disease, brain injury, or other insult leading to cerebral dysfunction. The dysfunction may be primary, as in diseases, injuries, and insults that affect the brain directly and selectively; or secondary, as in systemic diseases and disorders that attack the brain only as one of the multiple organs or systems of the body that are involved. Example, code F06.1, “Catatonic disorder due to known physiological condition”. The lesson to be learned is to acquire the knowledge and understanding of ICD-10 codes used by the practice. This is accomplished by taking a proactive approach and keeping an open mind. A lesson learned is an experience or outcome of a particular course of action. A positive outcome follows a positive course of study. Nancy Maguire, ACS, PCS, FCS, HCS-D, CRT, author of The Nancy Maguire GPS to ICD-10-CM Planning and Implementation Guide, is a nationally-renowned procedural and diagnostic coding instructor, bootcamp trainer, and workshop leader. She has spent more than 30 years as a hands-on coder and has authored countless coding articles and presentations. In her expansive career, she has transitioned from nursing, to coding, to practice management, auditing and consulting. Nancy served as Director of Coding and Reimbursement at UTMB in Galveston Texas for four years. She served the first two terms as president of AAPC in the early 1990s. Hear Nancy speak in two complimentary archived webinars on ICD-10 presented by Kareo medical billing software: How to Prepare for ICD-10/5010 to Reduce F41.1 (Anxiety Reaction) or Preparing for ICD-10-CM: The Nitty-Gritty of Diagnosis Coding	4	5	0	0	0	19	0.856808	19	1,486
Chronic pain has been recognized as pain that persists past normal healing time5 and hence lacks the acute warning function of physiological nociception.35 Usually pain is regarded as chronic when it lasts or recurs for more than 3 to 6 months.29 Chronic pain is a frequent condition, affecting an estimated 20% of people worldwide6,13,14,18 and accounting for 15% to 20% of physician visits.25,28 Chronic pain should receive greater attention as a global health priority because adequate pain treatment is a human right, and it is the duty of any health care system to provide it.4,13 The current version of the International Classification of Diseases (ICD) of the World Health Organization (WHO) includes some diagnostic codes for chronic pain conditions, but these diagnoses do not reflect the actual epidemiology of chronic pain, nor are they categorized in a systematic manner. The ICD is the preeminent tool for coding diagnoses and documenting investigations or therapeutic measures within the health care systems of many countries. In addition, ICD codes are commonly used to report target diseases and comorbidities of participants in clinical research. Consequently, the current lack of adequate coding in the ICD makes the acquisition of accurate epidemiological data related to chronic pain difficult, prevents adequate billing for health care expenses related to pain treatment, and hinders the development and implementation of new therapies.10,11,16,23,27,31,37 Responding to these shortcomings, the International Association for the Study of Pain (IASP) contacted the WHO and established a Task Force for the Classification of Chronic Pain. The IASP Task Force, which comprises pain experts from across the globe,19 has developed a new and pragmatic classification of chronic pain for the upcoming 11th revision of the ICD. The goal is to create a classification system that is applicable in primary care and in clinical settings for specialized pain management. A major challenge in this process was finding a rational principle of classification that suits the different types of chronic pain and fits into the general ICD-11 framework. Pain categories are variably defined based on the perceived location (headache), etiology (cancer pain), or the primarily affected anatomical system (neuropathic pain). Some diagnoses of pain defy these classification principles (fibromyalgia). This problem is not unique to the classification of pain, but exists throughout the ICD. The IASP Task Force decided to give first priority to pain etiology, followed by underlying pathophysiological mechanisms, and finally the body site. Developing this multilayered classification was greatly facilitated by a novel principle of assigning diagnostic codes in ICD-11, termed “multiple parenting.” Multiple parenting allows the same diagnosis to be subsumed under more than 1 category (for a glossary of ICD terms refer to Table 1). Each diagnosis retains 1 category as primary parent, but is cross-referenced to other categories that function as secondary parents. The new ICD category for “Chronic Pain” comprises the most common clinically relevant disorders. These disorders were divided into 7 groups (Fig. 1): (1) chronic primary pain, (2) chronic cancer pain, (3) chronic posttraumatic and postsurgical pain, (4) chronic neuropathic pain, (5) chronic headache and orofacial pain, (6) chronic visceral pain, and (7) chronic musculoskeletal pain. Experts assigned to each group are responsible for the definition of diagnostic criteria and the selection of the diagnoses to be included under these subcategories of chronic pain. Thanks to Bedirhan Üstün and Robert Jakob of the WHO, these pain diagnoses are now integrated in the beta version of ICD-11 (http://id.who.int/icd/entity/1581976053). The Task Force is generating content models for single entities to describe their clinical characteristics. After peer review overseen by the WHO Steering Committee,39 the classification of chronic pain will be voted into action by the World Health Assembly in 2017. 2. Classification of chronic pain Chronic pain was defined as persistent or recurrent pain lasting longer than 3 months. This definition according to pain duration has the advantage that it is clear and operationalized. Optional specifiers for each diagnosis record evidence of psychosocial factors and the severity of the pain. Pain severity can be graded based on pain intensity, pain-related distress, and functional impairment. 2.1. Chronic primary pain Chronic primary pain is pain in 1 or more anatomic regions that persists or recurs for longer than 3 months and is associated with significant emotional distress or significant functional disability (interference with activities of daily life and participation in social roles) and that cannot be better explained by another chronic pain condition. This is a new phenomenological definition, created because the etiology is unknown for many forms of chronic pain. Common conditions such as, eg, back pain that is neither identified as musculoskeletal or neuropathic pain, chronic widespread pain, fibromyalgia, and irritable bowel syndrome will be found in this section and biological findings contributing to the pain problem may or may not be present. The term “primary pain” was chosen in close liaison with the ICD-11 revision committee, who felt this was the most widely acceptable term, in particular, from a nonspecialist perspective. 2.2. Chronic cancer pain Pain is a frequent and debilitating accompaniment of cancer8 that as yet has not been represented in the ICD. The Task Force decided to list it as a separate entity because there are specific treatment guidelines.7,38 Chronic cancer pain includes pain caused by the cancer itself (the primary tumor or metastases) and pain that is caused by the cancer treatment (surgical, chemotherapy, radiotherapy, and others). Cancer-related pain will be subdivided based on location into visceral, bony (or musculoskeletal), and somatosensory (neuropathic). It will be described as either continuous (background pain) or intermittent (episodic pain) if associated with physical movement or clinical procedures. The treatment-related pain will be cross-referenced from the chapters on postsurgical pain and neuropathic pain. 2.3. Chronic postsurgical and posttraumatic pain Because pain that persists beyond normal healing is frequent after surgery and some types of injuries, the entity of postsurgical and posttraumatic pain was created. This is defined as pain that develops after a surgical procedure or a tissue injury (involving any trauma, including burns) and persists at least 3 months after surgery or tissue trauma26; this is a definition of exclusion, as all other causes of pain (infection, recurring malignancy) as well as pain from a pre-existing pain problem need to be excluded. In view of the different causality, as well as from a medicolegal point of view, a separation between postsurgical pain and pain after all other trauma is regarded as useful. Depending on the type of surgery, chronic postsurgical pain is often neuropathic pain (on average 30% of cases with a range from 6% to 54% and more).15 Pain including such a neuropathic component is usually more severe than nociceptive pain and often affects the quality of life more adversely.21 2.4. Chronic neuropathic pain Chronic neuropathic pain is caused by a lesion or disease of the somatosensory nervous system.20,22 The somatosensory nervous system provides information about the body including skin, musculoskeletal, and visceral organs. Neuropathic pain may be spontaneous or evoked, as an increased response to a painful stimulus (hyperalgesia) or a painful response to a normally nonpainful stimulus (allodynia). The diagnosis of neuropathic pain requires a history of nervous system injury, for example, by a stroke, nerve trauma, or diabetic neuropathy, and a neuroanatomically plausible distribution of the pain.22 For the identification of definite neuropathic pain, it is necessary to demonstrate the lesion or disease involving the nervous system, for example, by imaging, biopsy, neurophysiological, or laboratory tests. In addition, negative or positive sensory signs compatible with the innervation territory of the lesioned nervous structure must be present.36 Diagnostic entities within this category will be divided into conditions of peripheral or central neuropathic pain. 2.5. Chronic headache and orofacial pain The International Headache Society (IHS) has created a headache classification17 that is implemented in full in the chapter on neurology. This classification differentiates between primary (idiopathic), secondary (symptomatic) headache, and orofacial pain including cranial neuralgias. In the section on chronic pain, only chronic headache and chronic orofacial pain will be included. Chronic headache and chronic orofacial pain is defined as headaches or orofacial pains that occur on at least 50% of the days during at least 3 months. For most purposes, patients receive a diagnosis according to the headache phenotypes or orofacial pains that they currently present. The section will list the most frequent chronic headache conditions. The most common chronic orofacial pains are temporomandibular disorders,32 which have been included in this subchapter of chronic pain. Chronic orofacial pain can be a localized presentation of a primary headache.2 This is common in the trigeminal autonomic cephalalgias, less common in migraines, and rare in tension-type headache. Several chronic orofacial pains such as post-traumatic trigeminal neuropathic pain,3 persistent idiopathic orofacial pain, and burning mouth syndrome are cross-referenced to, eg, primary chronic pain and neuropathic pain. The temporal definition of “chronic” has been extrapolated from that of chronic headaches.1 2.6. Chronic visceral pain Chronic visceral pain is persistent or recurrent pain that originates from the internal organs of the head and neck region and the thoracic, abdominal, and pelvic cavities.24,33,34 The pain is usually perceived in the somatic tissues of the body wall (skin, subcutis, muscle) in areas that receive the same sensory innervation as the internal organ at the origin of the symptom (referred visceral pain).12 In these areas, secondary hyperalgesia (increased sensitivity to painful stimuli in areas other than the primary site of the nociceptive input) often occurs30; the intensity of the symptom may bear no relationship with the extent of the internal damage or noxious visceral stimulation.9 The section on visceral pain will be subdivided according to the major underlying mechanisms, ie, persistent inflammation, vascular mechanisms (ischemia, thrombosis), obstruction and distension, traction and compression, combined mechanisms (eg, obstruction and inflammation concurrently), and referral from other locations. Pain due to cancer will be cross-referenced to the chapter chronic cancer pain and pain due to functional or unexplained mechanisms to chronic primary pain. 2.7. Chronic musculoskeletal pain Chronic musculoskeletal pain is defined as persistent or recurrent pain that arises as part of a disease process directly affecting bone(s), joint(s), muscle(s), or related soft tissue(s). According to the constraints of the approach as described in the Introduction, this category is therefore limited to nociceptive pain and does not include pain that may be perceived in musculoskeletal tissues but does not arise therefrom, such as the pain of compression neuropathy or somatic referred pain. The entities subsumed in this approach include those characterized by persistent inflammation of infectious, autoimmune or metabolic etiology, such as rheumatoid arthritis, and by structural changes affecting bones, joints, tendons, or muscles, such as symptomatic osteoarthrosis. Musculoskeletal pain of neuropathic origin will be cross-referenced to neuropathic pain. Well-described apparent musculoskeletal conditions for which the causes are incompletely understood, such as nonspecific back pain or chronic widespread pain, will be included in the section on chronic primary pain. Irrespective of its etiology, chronic pain is a major source of suffering and requires special treatment and care. Our proposal may not represent a perfect solution for the classification of all manifestations of chronic pain. However, it does represent the first systematic approach to implementing a classification of chronic pain in the ICD. It is based on international expertise and agreement, and consistent with the requirements of the ICD regarding the structure and format of content models. The 7 major categories of chronic pain were identified after considerable research and discussion. They represent a compromise between comprehensiveness and practical applicability of the classification system. Several clinically important conditions that were neglected in former ICD revisions will now be mentioned, eg, chronic cancer pain or chronic neuropathic pain. Etiological factors, pain intensity, and disability related to pain will be reflected. With the introduction of chronic primary pain as a new diagnostic entity, the classification recognizes conditions that affect a broad group of patients with pain and would be neglected in etiologically defined categories. We hope that this classification strengthens the representation of chronic pain conditions in clinical practice and research and welcome comments to improve it further. Conflict of interest statement Q. Aziz has attended advisory board meetings for Almirall pharmaceuticals and Grunenthal. He has also received funding for clinical trials from Ono Pharmaceutical and Protexin. M.I. Bennett has received consultancy or speaker fees from Pfizer, Bayer, Astellas, and Grunenthal in the last 5 years. M. Cohen has received honoraria for contributions to educational programs from Mundipharma Pty Limited and Pfizer. S. Evers received honoraria (as speaker and/or member of advisory boards) and research grants within the past 5 years by AGA Medical (now St Jude), Allergan, Almirall, Astra Zeneca, Berlin-Chemie, CoLucid, Desitin, Eisai, GlaxoSmithKline, Ipsen Pharma, Menarini, MSD, Novartis, Pfizer, Reckitt-Benckiser, UCB. N.B. Finnerup has received speaker's honoraria from Pfizer, Grunenthal, and Norpharma, research grant from Grünenthal, and consultancy fee from Astellas and is member of the IMI “Europain” collaboration where industry members of this are: Astra Zeneca, Pfizer, Esteve, UCB-Pharma, Sanofi Aventis, Grünenthal, Eli Lilly, Boehringer Ingelheim, Astellas, Abbott, and Lundbeck. M.B. First on the faculty of the Lundbeck International Neuroscience Foundation. In the past 2 years, M.A. Giamberardino received research funding or honoraria (participation in Advisory Board) from Bayer Healthcare, Helsinn, and Epitech Group. S. Kaasa declares no conflict of interest related to this work. In the past year he received honoraria from Helsinn related to participation in Advisory Board. E. Kosek has received consultancy and speaker fees in the past 24 months from Eli Lilly and Company and Orion and has ongoing research collaborations with Eli Lilly and Company and Abbott and Pierre Fabre. M. Nicholas received honoraria for contributing to educational sessions for Mundipharma and Pfizer in the last 5 years. S. Perrot received honoraria as a speaker and/or member of the advisory board in the past 5 years from Pfizer, BMS, Grunenthal, Elli Lilly, Sanofi, Daichi-Sankyo, Astellas, and Mundipharma. He has received grant support from BMS. W. Rief received honoraria (as speaker and/or member of advisory boards on topics such as adherence, placebo mechanisms) within the past 5 years from Berlin Chemie, Astra Zeneca, Bayer, Heel (research grant). J. Scholz has received speaker fees from Convergence, GlaxoSmithKline, Pfizer, St Jude Medical, and Zalicus. He has served on advisory boards or consulted for Convergence, Pfizer, Sanofi Aventis, and Zalicus Pharmaceuticals. He has received grant support from GlaxoSmithKline and Pfizer. In the last 5 years, the Anaesthesiology Unit of the University of Western Australia, but not S. Schug personally, has received research and travel funding and speaking and consulting honoraria from bioCSL, Bionomics, Eli Lilly, Grunenthal, Janssen, Mundipharma, Pfizer, Phosphagenics and iX Biopharma within the last 2 years. B.H. Smith has received lecture and consultancy fees, on behalf of his institution, from Pfizer, Grunenthal, Eli Lilly, and Napp. He has received unconditional educational grants from Pfizer Ltd; and he has received travel and accommodation support from Napp. P. Svensson served as a paid consultant for Sunstar Suisse SA. R.-D. Treede has received speaker's honoraria, research grants or consultancy fees from AbbVie, Acron, Astellas, Bauerfeind, Boehringer Ingelheim, Grünenthal, Hydra, Mundipharma, and Pfizer and is a member of the IMI “Europain” collaboration where industry members of this are: Astra Zeneca, Pfizer, Esteve, UCB-Pharma, Sanofi Aventis, Grünenthal, Eli Lilly, Boehringer Ingelheim, Astellas, Abbott, and Lundbeck. J.W.S. Vlaeyen is a member of the PHILIPS advisory board on pain management and declares no conflicts of interest with regard to this work. S.-J. Wang has served on the advisory boards of Allergan and Eli Lilly, Taiwan. He has received speaking honoraria from local companies (Taiwan branches) of Pfizer, Elli Lilly, and GSK. He has received research grants from the Novartis Taiwan, Taiwan Ministry of Science and Technology, Taipei-Veterans General Hospital and Taiwan Headache Society. The other authors have no conflicts of interest to declare. The authors are members of the Classification of Pain Diseases Task Force of the International Association for the Study of Pain (IASP), which gave logistical and financial support to perform this work. We acknowledge the contributions of the following IASP Special Interest Groups (SIGs): Abdominal & Pelvic Pain SIG, Acute Pain SIG, Cancer Pain SIG, Neuropathic Pain SIG and the Orofacial Pain SIG, and the Classification Committee of the International Headache Society (IHS). Author contributions: R.-D. Treede, W. Rief, and A. Barke contributed equally to this topical review. Structure of the chapter on chronic pain Chronic pain (persistent or recurrent pain lasting longer than 3 months)These disorders have in part been renumbered as compared with the ICHD-3. †#5.3 is not part of the ICHD-3. - 1. Chronic primary pain - 1.1. Widespread chronic primary pain (including fibromyalgia syndrome) - 1.2. Localized chronic primary pain (including nonspecific back pain, chronic pelvic pain) - 1.x. Other chronic primary pain - 1.z. Chronic primary pain not otherwise specified - 2. Chronic cancer pain - 2.1. Chronic pain due to cancer and metastases - 2.2. Chronic chemotherapy-induced pain (primary parent: chronic neuropathic pain) - 2.3. Chronic pain due to cancer surgery (primary parent: chronic postsurgical and posttraumatic pain) - 2.4. Chronic pain due to radiotherapy - 2.x. Other chronic pain related to cancer - 2.z. Chronic cancer pain not otherwise specified - 3. Chronic postsurgical and posttraumatic pain - 3.1. Chronic postsurgical pain - 3.2. Chronic posttraumatic pain - 3.x. Other chronic postsurgical and posttraumatic pain - 3.z. Chronic postsurgical and posttraumatic pain not otherwise specified - 4. Chronic neuropathic pain - 4.1. Peripheral neuropathic pain - 4.2. Central neuropathic pain - 4.x. Other neuropathic pain - 4.z. Neuropathic pain not otherwise specified - 5. Chronic headache and orofacial pain - 5.1. Chronic primary headaches - 5.2. Chronic secondary headaches* - 5.3. Chronic orofacial pains† - 5.z. Headache and orofacial pain not otherwise specified* - 6. Chronic visceral pain - 6.1. Chronic visceral pain from persistent inflammation - 6.2. Chronic visceral pain from vascular mechanisms - 6.3. Chronic visceral pain from obstruction/distension - 6.4. Chronic visceral pain from traction/compression - 6.5. Chronic visceral pain from combined mechanisms - 6.6. Chronic visceral pain referred from other locations - 6.7. Chronic visceral pain from cancer (primary parent: chronic cancer pain) - 6.8. Functional or unexplained chronic visceral pain (primary parent: chronic primary pain) - 6.x. Other chronic visceral pain - 6.z. Chronic visceral pain not otherwise specified - 7. Chronic musculoskeletal pain - 7.1. Chronic musculoskeletal pain from persistent inflammation - 7.2. Chronic musculoskeletal pain from structural osteoarticular changes - 7.3. Chronic musculoskeletal pain due to disease of the nervous system (All neuropathic pain will be classified under 4. Chronic neuropathic pain. Here, other chronic musculoskeletal pain originating from diseases of the nervous system, eg, spastic pain will be listed.) - 7.4. Chronic nonspecific musculoskeletal pain (primary parent: chronic primary pain) - 7.x. Other chronic musculoskeletal pain syndromes - 7.z. Chronic musculoskeletal pain not otherwise specified . Benoliel R, Birman N, Eliav E, Sharav Y. The International Classification of Headache Disorders: accurate diagnosis of orofacial pain? Cephalalgia 2008;7:752–62. . Benoliel R, Eliav E, Sharav Y. Classification of chronic orofacial pain: applicability of chronic headache criteria. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:729–37. . Benoliel R, Zadik Y, Eliav E, Sharav Y. Peripheral painful traumatic trigeminal neuropathy: clinical features in 91 cases and proposal of novel diagnostic criteria. J Orofacial Pain 2012;26:49–58. . Bond M, Breivik H, Jensen TS, Scholten W, Soyannwo O, Treede RD. Pain associated with neurological disorders. In: Aarli JA, Dua T, Janca A, Muscetta A, editors. Neurological disorders: public health challenges. Geneva: WHO Press, 2006. p. 127–139. . Bonica JJ. The management of pain. Philadelphia: Lea & Febiger, 1953. . Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain 2006;10:287. . Caraceni A, Hanks G, Kaasa S, Bennett MI, Brunelli C, Cherny N, Dale O, De Conno F, Fallon M, Hanna M, Haugen DF, Juhl G, King S, Klepstad P, Laugsand EA, Maltoni M, Mercadante S, Nabal M, Pigni A, Radbruch L, Reid C, Sjogren P. Use of opioid analgesics in the treatment of cancer pain: evidence based recommendations from the EAPC. Lancet Oncol 2012;13:e58–68. . Caraceni A, Portenoy RK. An international survey of cancer pain characteristics and syndromes. IASP Task Force on Cancer Pain. International Association for the Study of Pain. PAIN 1999;82:263–74. . Cervero F. Visceral pain—central sensitization. Gut 2000;47:56–7. . Fillingim RB, Bruehl S, Dworkin RH, Dworkin SF, Loeser JD, Turk DC, Widerstrom-Noga E, Arnold L, Bennett R, Edwards RR, Freeman R, Gewandter J, Hertz S, Hochberg M, Krane E, Mantyh PW, Markman J, Neogi T, Ohrbach R, Paice JA, Porreca F, Rappaport BA, Smith SM, Smith TJ, Sullivan MD, Verne GN, Wasan AD, Wesselmann U. The ACTTION-American Pain Society Pain Taxonomy (AAPT): an evidence-based and multidimensional approach to classifying chronic pain conditions. J Pain 2014;15:241–49. . Finnerup NB, Scholz J, Attal N, Baron R, Haanpää M, Hansson P, Raja SN, Rice AS, Rief W, Rowbotham MC, Simpson DM, Treede RD. Neuropathic pain needs systematic classification. Eur J Pain 2013;17:953–6. . Giamberardino MA, Affaitati G, Costantini R. Referred pain from internal organs. In: Cervero F, Jensen TS, editors. Handbook of clinical neurology. Amsterdam: Elsevier, 2006. p. 343–61. . Goldberg DS, Summer JM. Pain as a global public health priority. BMC Public Health 2011;11:770. . Gureje O, von Korff M, Kola L, Demyttenaere K, He Y, Posada-Villa J, Lepine JP, Angermeyer MC, Levinson D, de Girolamo G, Iwata N, Karam A, Borges GLG, de Graaf R, Browne MO, Stein DJ, Haro JM, Bromet EJ, Kessler RC, Alonso J. The relation between multiple pains and mental disorders: results from the World Mental Health Surveys. PAIN 2008;135:82–91. . Haroutiunian S, Nikolajsen L, Finnerup NB, Jensen TS. The neuropathic component in persistent postsurgical pain: a systematic literature review. PAIN 2013;154:95–102. . Hart OR, Uden RM, McMullan JE, Ritchie MS, Williams TD, Smith BH. A study of National Health Service management of chronic osteoarthritis and low back pain. Prim Health Care Res Dev 2014;27:1–10. . Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition (beta). Cephalalgia 2013;33:629–808. . Institute of Medicine (IOM). Relieving pain in America: a blueprint for transforming prevention, care, education, and research. Washington, DC: The National Academies Press, 2011. Available at: http://books.nap.edu/openbook.php?record_id=13172 . Accessed 10 January 2015. . International Organization for the Study of Pain (IASP). List of Task Force Members. Available at: http://www.iasp-pain.org/AboutIASP/Content.aspx?ItemNumber=1997 . Accessed October 01, 2014 and archived: http://www.webcitation.org/6Szl4AxX4 . International Organization for the Study of Pain (IASP). Available at:(http://www.iasp-pain.org/Education/Content.aspx?ItemNumber=1698&navItemNumber=576 ). Accessed November 11, 2014 and archived: http://www.webcitation.org/6U0KsS4QV . Jensen MP, Chodroff MJ, Dworkin RH. The impact of neuropathic pain on health-related quality of life: review and implications. Neurology 2007;68:1178–82. . Jensen TS, Baron R, Haanpää M, Kalso E, Loeser JD, Rice AS, Treede RD. A new definition of neuropathic pain. PAIN 2011;152:2204–5. . Klepstad P, Kaasa S, Cherny N, Hanks G, de Conno F. Pain and pain treatments in European palliative care units. A cross sectional survey from the European Association for Palliative Care Research Network. Palliat Med 2005;19:477–84. . Knowles CH, Aziz Q. Basic and clinical aspects of gastrointestinal pain. PAIN 2009;141:191–209. . Koleva D. Pain in primary care: an Italian survey. Eur J Public Health 2005;15:475–79. . Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth 2008;101:77–86. . Manchikanti L, Falco FJE, Kaye AD, Hirsch JA. The disastrous but preventable consequences of ICD-10. Pain Physician 2014;E111–18. . Mäntyselkä P, Kumpusalo E, Ahonen R, Kumpusalo A, Kauhanen J, Viinamäki H, Halonen P, Takala J. Pain as a reason to visit the doctor: a study in Finnish primary health care. PAIN 2001;89:175–80. . Merskey H, Bogduk N. Classification of chronic pain. 2nd ed. Seattle: IASP Press, 1994. p. 1. . Procacci P, Zoppi M, Maresca M. Clinical approach to visceral sensation. In: Cervero F, Morrison JFB, editors. Visceral sensation: progress in brain research. Amsterdam: Elsevier, 1986. p. 21–7. . Rief W, Kaasa S, Jensen R, Perrot S, Vlaeyen JW, Treede RD, Vissers KC. The need to revise pain diagnoses in ICD-11. PAIN 2010;149:169–70. . Schiffman E, Ohrbach R, Truelove E, Look J, Anderson G, Goulet J-P, List T, Svensson P, Gonzalez Y, Lobbezoo F, Michelotti A, Brooks L, Ceusters W, Drangsholt M, Ettlin D, Gaul C, Goldberg LJ, Haythornthwaite JA, Hollender L, Jensen R, John M, De Laat A, de Leeuw R, Maixner W, van der Meulen M, Murray GM, Nixdorf DR, Palla S, Petersson A, Pionchon P, Smith B, Visscher CM, Zakrzewska J, Dworkin SF. Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications: Recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Groupdagger. J Oral Facial Pain Headache 2014;28:6–27. . Schwartz ES, Gebhart GF. Visceral Pain. Curr Top Behav Neurosci 2014;20:171–97. . Stein SL. Chronic pelvic pain. Gastroenterol Clin North Am 2013;42:785–800. . Treede RD. Entstehung der Schmerzchronifizierung. In: Baron R, Koppert W, Strumpf M, Willweber-Strumpf A, editors. Praktische Schmerztherapie. Heidelberg: Springer, 2011. p. 3–13. . Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, Hansson P, Hughes R, Nurmikko T, Serra J. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008;70:1630–5. . van den Beuken-van Everdingen MHJ, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol 2007;18:1437–49. . WHO. Cancer pain relief. Second edition. With a guide to opioid availability. Geneva: WHO, 1996. p. 36–37.	2	12	1	0	0	0	0.641815	1	6,992
ICD-10-CM Code K12 Stomatitis and related lesions Non-Billable CodeNon-Billable means the code is not sufficient justification for admission to an acute care hospital when used a principal diagnosis. Use a child code to capture more detail. ICD Code K12 is a non-billable code. To code a diagnosis of this type, you must use one of the four child codes of K12 that describes the diagnosis 'stomatitis and related lesions' in more detail. - K12 Stomatitis and related lesions NON-BILLABLE - BILLABLE K12.0 - BILLABLE K12.1 - BILLABLE K12.2 and - K12.3 NON-BILLABLE - K12.30 Oral mucositis (ulcerative), unspecified BILLABLE - K12.31 Oral mucositis (ulcerative) due to antineoplastic therapy BILLABLE - K12.32 Oral mucositis (ulcerative) due to other drugs BILLABLE - K12.33 Oral mucositis (ulcerative) due to radiation BILLABLE - K12.39 Other oral mucositis (ulcerative) BILLABLE The ICD code K12 is used to code Mouth ulcer A mouth ulcer (also termed an oral ulcer, or a mucosal ulcer) is an ulcer that occurs on the mucous membrane of the oral cavity. Mouth ulcers are very common, occurring in association with many diseases and by many different mechanisms, but usually there is no serious underlying cause. \|ICD 9 Code:\|\|528.9\| A mouth ulcer (in this case associated with aphthous stomatitis) on the labial mucosa (lining of the lower lip). Coding Notes for K12 Info for medical coders on how to properly use this ICD-10 code Additional Code Note: Use Additional CodeUse Additional Code note means a second code must be used in conjunction with this code. Codes with this note are Etiology codes and must be followed by a Manifestation code or codes. - Code to identify: - Alcohol abuse and dependence See code F10.- - Exposure to environmental tobacco smoke See code Z77.22 - Exposure to tobacco smoke in the perinatal period See code P96.81 - History of tobacco use See code Z87.891 - Occupational exposure to environmental tobacco smoke See code Z57.31 - Tobacco dependence See code F17.- - Tobacco use See code Z72.0 Code Type-1 Excludes: Type-1 ExcludesType-1 Excludes mean the conditions excluded are mutually exclusive and should never be coded together. Excludes 1 means "do not code here." - Cancrum oris - instead, use code A69.0 - Cheilitis - instead, use code K13.0 - Gangrenous stomatitis - instead, use code A69.0 - Herpesviral [herpes simplex] gingivostomatitis - instead, use code B00.2 - Noma - instead, use code A69.0 ICD-10-CM Alphabetical Index References for 'K12 - Stomatitis and related lesions' The ICD-10-CM Alphabetical Index links the below-listed medical terms to the ICD code K12. Click on any term below to browse the alphabetical index.	4	2	0	0	0	13	0.344326	13	746
The question of how to bill for a rapid flu test a and b is a common one, especially in pediatric practices. However, there are some key factors to consider when billing for this procedure. Listed below are some tips to remember while coding for this service. In order to avoid a misunderstanding between payers and providers, make sure you understand the process. Read the following for a clearer picture. The first step is to understand the terminology used for these tests. The term "rapid influenza test" refers to the process of identifying a patient's influenza virus infection using blood or other clinical specimens. This process is commonly known as an immunoassay. The MMWR stands for Morb Mortal Wkly Report. The CPT code for the test is 87804. The CPT code for a rapid flu test is 87804. The test is performed using a direct optical observation method. In this process, the influenza virus antigen is detected by the immune system. If the specimen is positive, the patient is said to have influenza. If the influenza virus is negative, the results can be interpreted as a false negative. In this case, the patient could still be suffering from the disease. The new codes were approved by the CPT Editorial Panel for immediate use. Normally, providers would use the CPT code 87631 to detect influenza and respiratory syncytial virus. But because of the public health emergency, this new code is needed to differentiate the COVID-19 from influenza A and B. Moreover, the availability of the multi-virus tests is expected to increase the testing capacity in the healthcare industry. In 2009, the Centers for Disease Control and Prevention (CDC) evaluated the rapid flu diagnostic tests. The tests were found to be safe and accurate. The findings were published in the MMWR, which is an acronym for Morb Mortal Wkly Report. Currently, 11 commercially available tests are listed as RIDTs. The MMWR policy statement requires that all labs use the same test code. The rapid flu diagnostic test a and b is a multi-virus testing technique used to identify influenza A and B viral antigens in respiratory specimens. These tests have many benefits, such as the ability to generate qualitative results in a clinically relevant time frame. They help clinicians distinguish COVID-19 from a variety of viruses. Fortunately, these multi-virus tests have become a common part of the healthcare industry. One of the cheapest ways to determine if you have the flu is to get a rapid flu test. This type of diagnostic test costs as little as $70 at a CVS MinuteClinic. It tests for Influenza A and B, two of the most common strains of influenza. The test also provides results in minutes and does not require culture. However, rapid flu tests are notorious for their high price tag and rate of false negatives, leaving many patients undiagnosed. The newer panels test for a range of illnesses, and these are often more expensive. The benefit of a rapid flu test is that the results are available in five minutes, compared to several hours with a standard lab. The test also costs less than $20, which is much better than paying $200 for a routine diagnostic test. A quick and accurate diagnosis will save you time and money. There are many advantages of a rapid influenza test, but the price is not the only factor. Some tests are more expensive than others, but it is worth the cost for a higher level of comfort and speed. The rapid flu test is the fastest and most accurate way to determine whether or not you have the flu. It requires just five minutes for a test to produce a diagnosis. These tests rely on samples from the nasal cavity and deep throat. These results are more accurate than a typical lab test, which takes up to two weeks to produce a diagnosis. In addition, they are more affordable than a traditional laboratory test, which can cost up to $200 or more. Despite the cost, rapid flu tests are still cheaper than a traditional laboratory test. These tests use samples from deep nasal swabs. They can give you the results you need in about five minutes, compared to a week or more with a traditional lab test. Additionally, they are more accurate and cost-effective than a conventional lab test. Moreover, the prices are more affordable than their lab counterparts. With a little research and effort, you can get a rapid flu test for as low as $5. These tests are more accurate than conventional tests and are more accurate than traditional lab tests. They cost about $15 for each test, which is much cheaper than traditional laboratory tests. If you have the flu, this test will give you an accurate diagnosis faster and more accurately. The results of the rapid flu test are more reliable than a standard laboratory test. They will also give you a better idea of which type of influenza is affecting you. So, if you want to make sure you don't have the flu, you should invest in a rapid influenza diagnostic kit. The rapid flu test price may seem high. But the benefits outweigh the price. The test takes just five minutes to complete and provides results much faster than a lab test. With a rapid influenza test, you'll find out if you have the virus or not in just a few minutes. These tests are the most effective way to diagnose the flu, and they can save you money. These tests are also easy to find and cost $5 or less. The lateral flow assay cassette is a common tool used in chemical testing. A sample is applied onto a strip in the application zone 110, which diffuses in the direction of flow 125 toward the analysis zone 130. This portion contains a test line 140 and a capture ligand, which captures the analyte of interest. The first and second calibration standards lines are placed in the same area to ensure that they are both equally loaded in the sample. The lateral flow immunoassay cassette is composed of a base 214, a test strip 201a, a conjugate pad 204a, and an absorbent pad 212. The test strip 211a includes a sample collection pad 216a, a test assay strip 206a, and a calibration strip 202b. The calibration strip 210b contains a sample application zone 202b and an absorbent pad 212b. The lateral flow chromatographic assay cassette is comprised of an absorbent test strip and a separate calibration strip. The test strip analyzes the analyte of interest in the experimental sample while the calibration strip runs at least one calibrating standard. The device also has a first application zone for the sample and a second sample application zone. These zones are located at different locations on the assay cassette. The testing apparatus couples the lateral flow chromatographic assay cassette to a handheld device. This device transmits light wavelengths designed to yield a detectable signal from the reporter (s). Then, the reporter interacts with the analyte of interest. The detector is placed in the vicinity of the swab. The results are then analyzed as a result of the reaction. The lateral flow assay cassette can be used for a variety of purposes. The lateral flow chromatographic assay cassette can be stored and packaged in a system 600. This system includes a sealed package containing the lateral-flow chromatographic assay cassette. It can contain a lateral-flow chromatographic assay, and can be stored in a clean environment. QR codes can be printed on the outside of the canister or foil pouch to indicate the level of contamination. The lateral flow assay cassette can be used to test multiple analytes. It contains a reagent strip and a label that detects the sample analyte. During the experiment, the cassette also contains an absorbent calibration strip. It runs at least one calibration standard at the same time as the experimental sample. The strips are separated by analytes and can be tested simultaneously or independently. The lateral flow assay cassette is often packaged in a packaging system 600. This system consists of a sealed package made of paper, foil, or plastic. This is the best way to protect the lateral flow chromatographic assay cassette and keep it safe from dust and moisture. A lateral-flow chromatographic assay cassette can also be used in a hospital for a diagnostic test. The resulting information will allow the laboratory to determine whether the sample contains a substance that is suspected of causing a disease. The lateral flow assay cassette 105 contains a LED light source that illuminates the analysis zone 130. This light source produces a detectable signal, which can be detected by a CCD or CMOS camera. Its detection ranges may be a few mmol/L for each analyte, but this process is not accurate if the reagent does not contain enough reagent. The lateral flow assay cassette is also packaged in a packaging system 600. The package is usually a foil pouch or a paper canister. This type of packaging allows for the cassette to be used in laboratories across a variety of sectors. Depending on the lateral flow assay, a labeled container can also be made out of plastic. The lateral-flow chromatographic assay is a very effective test for determining the presence of a specific analyte. The lateral flow chromatographic assay cassette is inserted into the testing device and illuminated with a light source. The sample is then analyzed to determine whether it contains the analyte of interest. In some cases, the lateral flow assay cassette is used to screen blood for alcohol and other drugs. The product can be customized to meet the needs of a laboratory. In addition to these, a lateral flow assay cassette can be used for many other purposes as well. A lateral flow cassette is used for packaging materials and consumables for diagnostic rapid test. It is a test strip that is designed to measure the blood pressure of an individual. Our company will develop new products with the rapid development of high-tech biology and medical technology and can be tailored to customer requirements. The fractionation step separates the plasmid DNA from the cellular debris and chromosomal DNA in the pellet. Iii. Solution I accommodates glucose, Tris and EDTA. Add 300 μl of isopropanol and blend gently to precipitate the DNA. Further purification by additional solvent extraction could additionally be required for experiments needing purer DNA (example – physical and chemical research, corresponding to melting curves). Dissolve 60.fifty five g of Tris in four hundred ml of distilled water. Adjust the pH to 7.5 with concentrated HCl. Add 1.zero ml of isopropanol to the microfuge tubes and leave at room temperature for two minutes. Proteinase K is used to degrade protein within the disrupted cell. Slowly take away the gel by running a spatula alongside the partitions of the gel tank. Coli chromosomal DNA, a partially renatured tangle at this step, is trapped in the precipitate. The plasmid DNA remains in answer. Add 1 ml of ice-cold 70% ethanol. Mix by inverting several instances. If the pellet is difficult to re-suspend, incubate 30 minutes at 65°C. Repeat until all or a lot of the pellet is dissolved (0.5 to 1 ml per gram of beginning material). Centrifuge for five minutes at 8000 rpm at 4°C. Remove residual RNA by adding zero.1% SDS and 1 μg/ml DNase-free RNase, incubating 1 hour at 37°C, and repeating ammonium acetate and ethanol precipitation of DNA and centrifugation. Add zero.5 quantity of seven.5 M ammonium acetate and a pair of volumes of one hundred pc ethanol. Freshly collected tissues may be saved instantly at -20°C or-80°C, or in liquid nitrogen. For DNA purification, the pH is usually 7 to 8, at which level all nucleic acids are found in the aqueous section. Mix equal volume of phenol with chloroform. Keep the mixture on ice and add 20 ml TE buffer, extract by shaking for 15 minutes. Remove the dust on the floor layer using a pipette. Repeat 4-5 instances. Add ml of TE buffer and retailer it on ice. The NucleoSpin Microbial DNA kit is designed for fast purification of highly pure genomic DNA from microorganisms (gram-negative and gram-positive micro organism, yeast, and fungi). The procedure is fast, simple and supplies reliably high DNA yields from a extensive range of microbial samples. The DNA is precipitated using alcohol. Gently add one-fifth volume of lysis buffer and blend by slowly inverting the tube several instances over a period of minutes at room temperature. If phases don't resolve well, add another quantity digestion buffer, omitting proteinase K, and repeat centrifugation. Re-suspend the cell pellet in chilly cell lysis buffer (approximately 108 cells/ml). In a recent regulatory action, the FDA exempted certain manufacturers of saline transport media from the requirements for manufacturing and distributing in vitro diagnostic devices. This exemption is meant to allow manufacturers to continue manufacturing and distributing these media while avoiding 510(k) submission and UDI requirements. Among other things, this exemption allows manufacturers to ship their products without complying with UDI and 510(k) requirements. The Saline Transport Media contains one sterile, 10mL sample collection tube filled with a non-toxic solution of Sodium Chloride in water. This solution provides no preservative properties and does not promote microbial contamination. Moreover, the sealed tubes do not leak during air transportation. This means that they can be used for a variety of research applications. It also offers the lowest price of all types of viral transport media. In the course of this study, six contrived samples were prepared for each type of transport media. All were negative controls. The samples were stored in refrigerated or frozen storage for up to two weeks. Aliquots were then retrieved from storage on days one, three, and seven, and tested according to both methods. In addition to VTM, alternative transport media were used as comparisons to the VTM. Sterile PBS/saline transport media are sterile and can be used for a variety of laboratory procedures. Commercial manufacturers must notify the FDA of their intention to distribute the product. The agency will also keep a list of the safest ways to manufacture and distribute these products. It will be beneficial for manufacturers to abide by this guidance. It will ensure safety and quality of the products. It is also a good way to minimize the risk of contamination to patients. In addition to COVID-19, a number of other policies apply to saline and PBS transport media. The FDA does not oppose the use and distribution of sterile PBS/saline transport media. However, commercial manufacturers must report the validation of their products to the agency. After the test, the media must be sterile and should not contain swabs, or any other foreign material. Sterile PBS/saline transport media are acceptable for use in medical devices. These devices must be validated by the FDA as sterile before they are distributed. To make sure that a product is sterile, manufacturers must validate the media before distributing it. These devices should be regulated and meet FDA standards. The products must be labeled according to their respective codes. They should be marketed for medical purposes and should be able to be transferred to a patient safely. High-complexity laboratories should be certified by the FDA. The use of VTM/PBS is allowed in laboratories that are certified under CLIA and perform high-complexity tests. The use of saline transport media is not prohibited for clinical labs, but it is prohibited in certain circumstances. As long as the device meets the standards, it should be safe to use. A lab with a CLIA-certified facility is not required to use saline transport media. Ruhof viral transport media is a 3 mL solution used for transportation, preservation, and collection of viruses. This medium is made by the Ruhof Corporation and is available for purchase from a variety of sources. This product is suitable for use in a wide variety of applications, including laboratory research and clinical laboratories. For further information, visit the Ruhof Corporation website. Its products are offered at competitive prices and free shipping. The Active Viral Transport Medium by the Ruhof Corporation is a specialized liquid designed to preserve and transport viruses. The Nasal Flocked Swab is a nasal cell specimen collection device intended for use in clinical diagnostics. Its perpendicular nylon fibers act as a soft brush to collect the specimen cells and fall into a liquid medium. This system is recommended for patients with a nasal bleed, cough, or croup. A virus can be preserved using Ruhof Active Viral Transport Media, which is specifically made for this application. The Nasal Flocked Swab is a cell specimen collection device designed for Nasopharyngeal disease and is used in clinical diagnostics. It is designed with a perpendicular nylon fiber structure that acts like a soft brush and allows specimen cells to fall into the liquid medium. This solution can be used for a variety of infectious diseases, including HBV and HIV. A virus can be transported to a lab in various ways, including by using sterile transport media. The COVID-19 Transport Media Policy addresses all types of infectious disease specimens, as well as the preparation and testing of viral antigens and RNAs. Generally, this medium can be made from PBS/saline and is sterile. In the case of a non-sterile Viral Transport Medium, the COVID-19 Transparency Policy will apply. The COVID-19 Transport Media Policy covers all types of infectious disease specimens, including those that have been infected by influenza. In the same way, all kinds of infectious disease samples must be sterile to ensure that they are safe for testing. For the most accurate and reliable diagnosis, the COVID-19 Viral Transport Media Policy is applicable to all laboratory types. It covers the preparation of all three kinds of inactivated viral transport media. The COVID-19 Transport Media Policy applies to all types of infectious disease specimens. It also addresses the preparation and testing of PBS/saline and viral transport media. It also describes the product codes for inactivated and uninfected VTM. Once the application process is complete, the FDA will acknowledge the email and provide appropriate guidance. The company's product code must be stated on the packaging. While the CDC's SOP is specific to the production of VTM, the FDA has no objections to commercial manufacturers' use and distribution of this product. However, a commercial manufacturer may want to develop and validate their VTM formulations in a way that differs from the SOP. It's important to follow the SOP to avoid contamination. It is essential to follow the SOP when making a VTM. Many parasitic protozoa are transmitted by arthropods, whereby multiplication and transformation into the infectious stage happen in the vector. These organisms are obligate intracellular parasites, rod-shaped to coccoid, that reproduce by binary transverse fission. Garber TR, Gonias SL, Webb DJ. Interleukin-4 and IL-10 bind covalently to activated human alpha2-macroglobulin by a mechanism that requires Cys949. The steps of the indirect ELISA are equivalent to the direct ELISA, aside from a further wash step and the kinds of antibody added after the buffer is eliminated. Indirect ELISA requires two antibodies, a main detection antibody that sticks to the protein of curiosity and a secondary enzyme-linked antibody complementary to the first antibody. The main antibody is added first, followed by a wash step, and then the enzyme-conjugated secondary antibody is added and incubated. After this, the steps are the same as the direct ELISA, which features a wash step, the addition of substrate, and detection of a color change. ELISAs are carried out in polystyrene plates, sometimes in 96-well plates coated to bind protein very strongly. When used in a easy indirect ELISA, recombinant 3D can differentiate contaminated from naive cattle . The sensitivity of the check is only barely decrease than the standard liquid phase blocking ELISA of Hamblin et al. and the specificity is approximately 95%. Moreover, the 3D antibody exams can be utilized to watch viral exercise in massive cattle populations and for certification of FMDV free animals for import and/or export testing . Whereas the following analysis showed that repeatedly vaccinated animals can develop antibodies to 3D, which reveal 3D is inadequate to differentiate an infection from vaccination. It is, therefore, an important a part of the epidemiological survey to evaluate frequently the antigenic traits of area isolates. In this evaluate, the ELISA methodology and its utilization in the identification, detection and quantification of viral particle or viral antigens or particular antibodies are mentioned. The newly reagent and expertise, which show great promise however continues to be in the early phases of development was described as nicely. Multiplex arrays have been recently developed from conventional ELISA assays with the aim of measuring a quantity of cytokines in the same sample at the identical time. ELISA based strategies are available and used clinically for testing for the early phases of cancers – together with ovarian and breast cancer. A variety of variations of ELISA have been developed, allowing qualitative detection or quantitative measurement of either antigen or antibody. Enzyme linked secondary antibody which is particular to the primary antibody is added. Health care personnel who perform the take a look at are skilled laboratory technicians who use special kits that measure the antigens' interactions with the antibodies in the package. This article will focus on the essential rules, procedures, and medical significance of the ELISA. Ss-NIE/Ss-IR recombinant antigens have been efficiently adapted to varied diagnostic platforms including immunoblots, enzyme linked immunosorbent assays , and Luciferase Immunoprecipitation Assay . Although LIPS is a extremely effective system, scientific laboratories have extra familiarity with performing ELISAs. The 1st step is to coat the ELISA plate withcapture antibody, any excess, unbound antibody is then washed from the plate. The seize antibody is an antibody raised towards the antigen of interest. The IgG and IgG4 assays were 99% and 96% delicate, respectively, and 99% and 100 percent specific, respectively. Neither the IgG or IgG4 assay confirmed cross reactions with sera from these contaminated with different helminths. Although ELISA values did decline post-treatment few returned to ranges beneath the cutoff for infection. The methodology may be also used to watch the degrees of pharmaceutical drug concentrations in patients present process remedy, for instance, antidrug antibodies in rheumatoid arthritis and inflammatory bowel disease sufferers. This leads to the formation of Ag-Ab complex which are then added to the wells which were coated with the same antigens. The extra antigen within the sample, extra major antibody will bind to the pattern antigen. An enzyme conjugated with an antibody reacts with a colorless substrate to generate a coloured reaction product. A variety of enzymes have been employed for ELISA, together with alkaline phosphatase, horseradish peroxidase, and B-galactosidase. NVD is an avian virus that can be handed to people and relying on the strain present, NDV disease can vary in severity from reasonable respiratory dysfunction to diarrhea and other life-threatening signs. From essentially the most deadly strains of NDV to more and more much less extreme strains , ELISA is used to monitor their presence within a population, aiding the coordination of vaccination programs, in addition to identifying any NDV contaminated flocks. ELISA is popularly used in the meals trade to detect the presence of allergens for legally required ingredient labeling. Then, Ko et al. reported rP13C ELISA in 2009, which explored the recombinant protein expressed in insect cells as a diagnostic antigen. The higher endpoint titers than LPB-ELISA and virus neutralization take a look at was represented within the measure of sera from goats challenged with FMDV post-vaccination. FMD is caused by FMD virus , a virus within the genus Aphthovirus within the household Picornaviridae . The genome is over 8 kb in length and encode four structural proteins that form an icosahedrical capsid , and a complete of ten mature non-structural proteins (L, 2A, 2B, 2C, 3A, 3B, 3C, 3D; or some advanced, corresponding to 3AB or 3ABC). Though the genome of FMDV is small, it has a high mutation fee and spontaneous. In FMDV, structural proteins are more variable than non-structural proteins. Therefore, researchers are all the time conscious of the temperature the sample is being uncovered to. Because analysis circumstances differ relying on a quantity of components, these moveable dry bathtub incubator china come in an enormous collection comprising different fashions, types, and sizes. Depending in your facility's requirements and the research processes you interact in, you will find probably the most acceptable portable dry tub incubator china on Alibaba.com. Our quality is recognized by overseas markets, and the utilization of our merchandise is ideal. 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The MK-10/MK-20 Dry Bath Incubator is a microprocessor-controlled product utilizing advanced thermoelectric method. Specifications Model MK-10 MK-20 Temperature Control Range RT+5°C~100°C -10°C~100°C Timing Range 1min~99h59min 1min~99h59min Temp. When moving downstream, the water pushes the canoe, growing its velocity, so it's better to stay in the midst of the stream to maximise this effect. Laminar move is characterized by clean circulate of the fluid in layers that don't combine. (1799–1869), who derived it in an attempt to grasp the circulate of blood by way of the body. If viscosity is zero, the fluid is frictionless and the resistance to flow is also zero. In this image principal cells could be simply recognized by their small microprojections into the lumen and by the presence of a single cilium. The sort A-ICs have a big luminal floor lined mostly with microplicae, while a kind B-IC has a more angular mobile outline and smaller apical microvilli (original magnification, ×5500). This transmission electron micrograph of rat cortical accumulating duct illustrates further the 2 configurations of intercalated cells. So should you just haven’t been designing round and flat oval spiral duct since you couldn’t find the best symbols, give us a call. You’re going to get extra turbulence, and turbulence is bad – you don’t even should be an engineer to know these square corners of rectangular ductwork trigger far more turbulence than no corners or rounded corners . We all type of know without trying it that placing a rectangular drain line downstream of your toilet would just about guarantee common visits from the plumber. The entry into the lacrimal sac most often occurs obliquely, which types the valve of Rosenmueller. While this isn't a valve per se, the angulation of the common canaliculus because it enters the sac prevents retrograde flux and acts in a valve-like manner. This exercise will handle nasolacrimal duct obstruction , which regularly results in intractable, bothersome epiphora. In longstanding NLDO, mucus can accumulate, resulting in a mucocele in the nasolacrimal sac or even acute or persistent dacryocystitis. Lacrimal surgical procedure to revive tear drainage is normally the definitive treatment and involved one of many types of dacryocystorhinostomy. The lacrimal gland is a compound tubuloacinar gland, comprised of lobules - which are formed by a number of acini. What is test strip cutter? The test strip cutter is specially designed for the manufacture of lateral flow detection kits, which can cut the sheet into strips. Accessory ducts could drain into the common hepatic duct, the CBD, the cystic duct, or the gallbladder . They can be too small to resolve by imaging but, if seen, must be included within the report if surgery is planned, since overlooking them at surgery could result in an insidious bile leak. Like most of the intra-abdominal viscus, the gallbladder has three distinct layers inside its wall. A stone is the most typical filling defect throughout the biliary tree and may be primary, arising de novo inside the biliary ducts, or secondary, arising from gallbladder stones passing into the CBD. Primary choledocholithiasis usually results from bile stasis and an infection. Ultrasonography is incessantly the preliminary examine for evaluating the gallbladder and biliary system. A sonogram can normally be obtained rapidly, is cost-effective, doesn't use ionizing radiation, and is highly sensitive and specific at assessing gallstones and the presence of biliary dilatation. The nasolacrimal duct consists of a 12-mm superior intraosseous portion and a 5-mm inferior membranous portion. At the posterior lacrimal crest, the orbital periosteum splits to envelop the lacrimal sac as a covering known as the lacrimal fascia. This periosteum then continues inferiorly to surround the nasolacrimal duct. Between the lacrimal fascia and the lacrimal sac lies a venous plexus. The orbital septum attaches to the medial orbital wall at the posterior lacrimal crest, so the lacrimal sac is a preseptal structure. In most individuals, the horizontal portion of the canaliculi converges to type the common canaliculus. Canaliculi pierce the lacrimal fascia before coming into the lacrimal sac. At its entrance to the lacrimal sac, the widespread canaliculus could dilate barely, forming the sinus of Maier. With this hepatic portal circulation, all blood from the alimentary canal passes through the liver. [newline]This largely explains why the liver is the commonest website for the metastasis of cancers that originate within the alimentary canal. An increased incidence of frequent bile duct stone formation and recurrence in those with low insertion of cystic duct was proposed . Biliary tract stones were seen in one-quarter of cases with posterior and anterior insertions in a latest examine . The relationship between CD insertion variations and choledocholithiasis requires addressing. When such 100-mm webs are later slit to typical widths of 10 mm, this sort of processing can obtain effective throughput in the same range as for distributed processes. Lateral-flow tests have historically been manufactured in relatively low volumes using a batch-processing approach, with a typical manufacturing line producing someplace between 2 million and 10 million devices per 12 months. The substrates used for batch processing could be in either a sheet or strip format, and are often about 300 mm in length. At check line, analyte-labeled antibody advanced is captured by one other antibody which is primary to the analyte. Analyte becomes sandwiched between labeled and first antibodies forming labeled antibody-analyte-primary antibody complicated. Excess labeled antibody will be captured at the control zone by secondary antibody. Intensity of shade at take a look at line corresponds to the quantity of target analyte and is measured with an optical strip reader or visually inspected. Complementing that work is one other of our initiatives referred to as Advanced Technology Platforms (RADx-ATP). It still needs validation, emergency use authorization, a little bit of manufacturing optimization. But we've different platforms out there which might be much nearer to commercialization, and RADx-ATP could presumably be very impactful in getting a few of those applied sciences out earlier. Where MT is the whole magnetization measured by AGFM, Ms is magnetization at saturation of particles (40 emu/g), ρ is particle density (2 g/cm3), and V is particle volume (4.2x10-12 mm3). The companies throughout the BBI Group offer a portfolio of products and services which may be delivered to the diagnostic and life science industries globally. A NeuroTrace CM-DiI tissue-labeling paste is also out there (N22883, see below under CM-DiI). These pastes are ready to make use of as equipped and could be applied directly to stay or mounted tissue specimens utilizing the tip of a needle. This methodology of application improves the penetration of the dye into bundled neurons, labeling axons both on and under the surface. In comparable conditions, direct application of dye crystals or microinjection of concentrated options will only label neurons on the surface. This labeling technique has additionally been discovered to extend the speed of dye transport by 50–80% (H. Richard Koerber, University of Pittsburgh School of Medicine, private communication). No syringe required to load the antibody resolution, minimising dead quantity and lack of reagents. At their simplest, they're dipsticks with a sample software pad at one end, a reading zone where the signal is generated within the middle and an absorbent materials at the different finish. Tests could also be included into housings that help greater performance, branding and user-centric design goals. All exams have been carried out in wells of a 96 nicely microtiter plate and took lower than 20 minutes to complete. These included, seize antibody, detection conjugate, assay buffer circumstances, and wish to block the membrane. The thickness of the membrane layer could decrease and enhance in any appropriate method, for example stepwise or steadily. Preferably, the thickness of the membrane layer is steadily lowering from the thickness of the detection zone to the thickness of the non-detection zone. Reference herein to steadily reducing is to a lower with a gradient and never stepwise, i.e. a decrease with a finite tangent . More ideally, the thickness is lowering with at most 300% (3 µm lower in thickness over 1 µm membrane length), even more ideally with at most 200%, much more ideally the decrease is in the range of from 30 to 100 percent. The membrane arrangement can advantageously be applied in a solid part lateral move immunoassay. Important parameters characterizing a great membrane materials are the capillary forces, as well as the benefit of binding and immobilizing proteins necessary for subsequent choice, reaction and detection. A vary of nitrocellulose pore sizes are available, from zero.05 to 12 μm. However, because the pores usually are not equally distributed , capillary flow time is a extra correct parameter and it ought to be used when deciding on the simplest strip materials. The capillary move time is the time required for the liquid to journey to and utterly fill the strip of the membrane. In the center of the lateral move is situated an extra or separate zone, which has a discrete membrane, in fluidic communication with the pattern move. The flow-rate management zone may be configured as an interchangeable, separate assembly or component that both the manufacturer or ultimate consumer can tailor for specific purposes. The 35 bp oligonucleotide probe sequence contained an 18-atom hexa-polyethyleneglycol internal spacer and 15 bp polyA spacer to maximise loading of oligonucleotides onto the gold nanoparticles . The oligonucleotides (25 µL, zero.1 mM) were incubated for half-hour with TCEP-HCl (10 µL, a hundred mM) in a complete volume of 110 µL to reduce the dithiol bonds. A 600 µL quantity of 60 nm gold colloid on the provided focus was added to the response and incubated overnight on a rotisserie. A three.57 µL volume of 2% SDS was added to the reaction to reach a last SDS focus of zero.01%. After half-hour of incubation, five eleven.57 µL volumes of two M NaCl were added to the answer, separated by 2-hour intervals, to achieve a complete NaCl concentration of zero.15 M. The following day, the GNPs had been centrifuged and washed 4 instances with 1 mL of zero.15 M NaCl, zero.01% SDS. Membrane layer 2 has a thickness 7 in detection zones 5 and a thickness eight exterior the detection zones (in the non-detection zones). Upstream of every detection zone 5, the thickness of membrane layer 2 is lowering from thickness 8 to thickness 7. Membrane arrangement 1 has a thickness 9 that's constant over the entire size of membrane arrangement 1. Reference herein to upstream is with reference to the lateral flow direction. The present research has efficiently fabricated an alternate response membrane for LFA by thorough hydrolysis of electrospun PCL nanofibers with NaOH treatment to introduce supporting features of lateral flow. The focus and period of NaOH therapy didn't influence the bodily properties of nanofibers, i.e., average fiber diameter, common pore measurement and porosity. The distinguishing features of those carbocyanine and aminostyryl tracers are summarized in Summary of Molecular Probes lipophilic carbocyanine and aminostyryl tracers—Table 14.3. Other lipophilic probes described in Probes for Lipids and Membranes—Chapter 13 have also been used as tracers for liposomes. N economical liquid dishing out system that permits everyone to do research on lateral flow assays and develop their own tests. This machine is particularly suited for R&D laboratories and start-ups, the place fast prototyping instances, low costs and small consumption of reagents are important.	2	27	6	0	0	0	0.551175	6	8,695
\|Classification and external resources\| Depersonalization disorder (DPD), also known as depersonalization-derealization syndrome, is a mental disorder in which the person has persistent or recurrent feelings of depersonalization and/or derealization. Symptoms can be classified as either depersonalization or derealization. Depersonalization is described as feeling disconnected or estranged from one's self. Individuals experiencing depersonalization may report feeling as if they are an outside observer of their own thoughts or body, and often report feeling a loss of control over their thoughts or actions. In some cases, individuals may be unable to accept their reflection as their own, or they may have out-of-body experiences. While depersonalization is a sense of detachment from one's self, derealization is described as detachment from one's surroundings. Individuals experiencing derealization may report perceiving the world around them as foggy, dreamlike/surreal, or visually distorted. In addition to these depersonalization-derealization disorder symptoms, the inner turmoil created by the disorder can result in depression, self-harm, low self-esteem, anxiety attacks, panic attacks, phobias, etc. It can also cause a variety of physical symptoms, including chest pain, blurry vision, visual snow, nausea, and the sensation of pins and needles in one's arms or legs. Depersonalization-derealization disorder is thought to be caused largely by severe traumatic lifetime events, including childhood abuse, accidents, natural disasters, war, torture, and bad drug experiences. It is unclear whether genetics play a role; however, there are many neurochemical and hormonal changes in individuals with depersonalization disorder. The disorder is typically associated with cognitive disruptions in early perceptual and attentional processes. Diagnostic criteria for depersonalization-derealization disorder includes, among other symptoms, persistent or recurrent feelings of detachment from one's mental or bodily processes or from one's surroundings. A diagnosis is made when the dissociation is persistent and interferes with the social and/or occupational functions of daily life. However, accurate descriptions of the symptoms are hard to provide due to the subjective nature of depersonalization/derealization and person's ambiguous use of language when describing these episodes. In the DSM-5 it was combined with Derealization Disorder and renamed to Depersonalization/Derealization Disorder (DDPD). In the DSM-5 it remains classified as a dissociative disorder, while in the ICD-10 it is called depersonalization-derealization syndrome and classified as a neurotic disorder. Although the disorder is an alteration in the subjective experience of reality, it is not a form of psychosis, as the person maintains the ability to distinguish between their own internal experiences and the objective reality of the outside world. During episodic and continuous depersonalization, the person can distinguish between reality and fantasy. In other words, their grasp on reality remains stable at all times. While depersonalization-derealization disorder was once considered rare, lifetime experiences with the disorder occur in approximately 1%–2% of the general population. The chronic form of this disorder has a reported prevalence of 0.8 to 1.9%. While these numbers may seem small, depersonalization/derealization experiences have been reported by a majority of the general population, with varying degrees of intensity. While brief episodes of depersonalization or derealization can be common in the general population, the disorder is only diagnosed when these symptoms cause significant distress or impair social, occupational, or other important areas of functioning. The core symptom of depersonalization-derealization disorder is the subjective experience of "unreality in one's self," or detachment from one's surroundings. People who are diagnosed with depersonalization also experience an urge to question and think critically about the nature of reality and existence. Individuals who experience depersonalization can feel divorced from their own personal physicality by sensing their body sensations, feelings, emotions and behaviors as not belonging to themselves. As such, a recognition of one's self breaks down. Depersonalization can result in very high anxiety levels, which can intensify these perceptions even further. Individuals with depersonalization describe feeling disconnected from their physicality; feeling as if they are not completely occupying their own body; feeling as if their speech or physical movements are out of their control; feeling detached from their own thoughts or emotions; and experiencing themselves and their lives from a distance. While depersonalization involves detachment from one's self, individuals with derealization feel detached from their surroundings, as if the world around them is foggy, dreamlike, or visually distorted. Some people with depersonalization disorder also have visual alterations such as rapid fluctuations in light. While the exact cause of these perceptual changes has not been determined, it is thought that they may be due to previous drug use. These perceptual changes differ from true hallucinatory phenomena, as they are closer to being optical distortions or illusions rather than psychotic breaks from reality. Individuals with the disorder commonly describe a feeling as though time is "passing" them by and they are not in the notion of the present. These experiences which strike at the core of a person's identity and consciousness may cause a person to feel uneasy or anxious. Factors that tend to diminish symptoms are comforting personal interactions, intense physical or emotional stimulation, and relaxation. Distracting oneself (by engaging in conversation or watching a movie, for example) may also provide temporary relief. Some other factors that are identified as relieving symptom severity are diet and/or exercise, while alcohol and fatigue are listed by some as worsening their symptoms. First experiences with depersonalization may be frightening, with patients fearing loss of control, dissociation from the rest of society and functional impairment. The majority of people with depersonalization-derealization disorder misinterpret the symptoms, thinking that they are signs of serious psychosis or brain dysfunction. This commonly leads to an increase of anxiety experienced by the patient, and obsession, which contributes to the worsening of symptoms. Occasional, brief moments of mild depersonalization can be experienced by many members of the general population; however, depersonalization-derealization disorder occurs when these feelings are strong, severe, persistent, or recurrent and when these feelings interfere with daily functioning. The exact cause of depersonalization is unknown, although biopsychosocial correlations and triggers have been identified. Childhood interpersonal trauma – emotional abuse in particular – is a significant predictor of a diagnosis. The most common immediate precipitators of the disorder are severe stress; major depressive disorder and panic; and hallucinogen ingestion. People who live in highly individualistic cultures may be more vulnerable to depersonalization, due to threat hypersensitivity and an external locus of control. One cognitive behavioral conceptualization is that misinterpreting normally transient dissociative symptoms as an indication of severe mental illness or neurological impairment leads to the development of the chronic disorder. This leads to a vicious cycle of heightened anxiety and symptoms of depersonalization and derealization. Not much is known about the neurobiology of depersonalization disorder; however, there is converging evidence that the prefrontal cortex may inhibit neural circuits that normally form the substrate of emotional experience. A PET scan found functional abnormalities in the visual, auditory, and somatosensory cortex, as well as in areas responsible for an integrated body schema. In an fMRI study of DPD patients, emotionally aversive scenes activated the right ventral prefrontal cortex. Participants demonstrated a reduced neural response in emotion-sensitive regions, as well as an increased response in regions associated with emotional regulation. In a similar test of emotional memory, depersonalization disorder patients did not process emotionally salient material in the same way as did healthy controls. In a test of skin conductance responses to unpleasant stimuli, the subjects showed a selective inhibitory mechanism on emotional processing. Depersonalization disorder may be associated with dysregulation of the hypothalamic-pituitary-adrenal axis, the area of the brain involved in the "fight-or-flight" response. Patients demonstrate abnormal cortisol levels and basal activity. Studies found that patients with DPD could be distinguished from patients with clinical depression and posttraumatic stress disorder. The symptoms are sometimes described by those with neurological diseases, such as amyotrophic lateral sclerosis, Alzheimer's, multiple sclerosis (MS), neuroborreliosis (Lyme disease), etc., that directly affect brain tissue. It has been thought that depersonalization has been caused by a biological response to dangerous or life-threatening situations which causes heightened senses and emotional neutrality. If this response is applied in real life, non-threatening situations, the result can be shocking to the individual. Although the use of cannabis can lead to symptoms of depersonalization, the DSM-5 excludes cases of depersonalization due to using substances, including episodes of post-marijuana or post-psychotomimetics depersonalization. Depersonalization disorder is classified differently in the DSM-IV-TR and in the ICD-10: In the DSM-IV-TR this disorder it is seen as a dissociative disorder; in the ICD-10 as an independent neurotic disorder. Whether depersonalization disorder should be characterized as a dissociative disorder can be discussed. Diagnosis is based on the self-reported experiences of the person followed by a clinical assessment. Psychiatric assessment includes a psychiatric history and some form of mental status examination. Since some medical and psychiatric conditions mimic the symptoms of DPD, clinicians must differentiate between and rule out the following to establish a precise diagnosis: temporal lobe epilepsy, panic disorder, acute stress disorder, schizophrenia, migraine, drug use, brain tumour or lesion. No laboratory test for depersonalization-derealization disorder currently exists. The diagnosis of depersonalization disorder can be made with the use of the following interviews and scales: The Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D) is widely used, especially in research settings. This interview takes about 30 minutes to 1.5 hours, depending on individual's experiences. The Dissociative Experiences Scale (DES) is a simple, quick, self-administered questionnaire that has been widely used to measure dissociative symptoms. It has been used in hundreds of dissociative studies, and can detect depersonalization and derealization experiences. The Dissociative Disorders Interview Schedule (DDIS) is a highly structured interview which makes DSM-IV diagnoses of somatization disorder, borderline personality disorder and major depressive disorder, as well as all the dissociative disorders. It inquires about positive symptoms of schizophrenia, secondary features of dissociative identity disorder, extrasensory experiences, substance abuse and other items relevant to the dissociative disorders. The DDIS can usually be administered in 30–45 minutes. The Cambridge Depersonalization Scale (CDS) is a method for determining the severity of depersonalization disorder. It has been proven and accepted as a valid tool for the diagnosis of depersonalization disorder in a clinical setting. It is also used in a clinical setting to differentiate minor episodes of depersonalization from actual symptoms of the disorder. Due to the success of the CDS, a group of Japanese researchers underwent the effort to translate the CDS into the J-CDS or the Japanese Cambridge Depersonalization Scale. Through clinical trials the Japanese research team successfully tested their scale and determined its accuracy. One limitation is that the scale does not allow for the differentiation between past and present episodes of depersonalization. It should also be noted that it may be difficult for the individual to describe the duration of a depersonalization episode, and thus the scale may lack accuracy. The project was conducted in the hope that it would stimulate further scientific investigations into depersonalization disorder. The diagnostic criteria defined in section 300.6 of the Diagnostic and Statistical Manual of Mental Disorders are as follows: - Longstanding or recurring feelings of being detached from one's mental processes or body, as if one is observing them from the outside or in a dream. - Reality testing is unimpaired during depersonalization - Depersonalization causes significant difficulties or distress at work, or social and other important areas of life functioning. - Depersonalization does not only occur while the individual is experiencing another mental disorder, and is not associated with substance use or a medical illness. The DSM-IV-TR specifically recognizes three possible additional features of depersonalization disorder: - Derealization, experiencing the external world as strange or unreal. - Macropsia or micropsia, an alteration in the perception of object size or shape. - A sense that other people seem unfamiliar or mechanical. Dissociation is defined as a "disruption in the usually integrated functions of consciousness, memory, identity and perception, leading to a fragmentation of the coherence, unity and continuity of the sense of self. Depersonalisation is a particular type of dissociation involving a disrupted integration of self-perceptions with the sense of self, so that individuals experiencing depersonalisation are in a subjective state of feeling estranged, detached or disconnected from their own being." In ICD-10, this disorder is called depersonalization-derealization syndrome F48.1. The diagnostic criteria are as follows: - 1. one of the following: - depersonalization symptoms, i.e. the individual feels that his or her feelings and/or experiences are detached, distant, etc. - derealization symptoms, i.e. objects, people, and/or surroundings seem unreal, distant, artificial, colourless, lifeless, etc. - 2. an acceptance that this is a subjective and spontaneous change, not imposed by outside forces or other people (i.e. insight) The diagnosis should not be given in certain specified conditions, for instance when intoxicated by alcohol or drugs, or together with schizophrenia, mood disorders and anxiety disorders. Primary depersonalization disorder is mostly refractory to current treatments. The disorder lacks effective treatment in part because it has been neglected by the psychiatric community because funding has mainly been allocated to the search for cures of other illnesses, like alcoholism. However, recognizing and diagnosing the condition may in itself have therapeutic benefits, considering many patients express their problems as baffling and unique to them, but are in fact: one, recognized and described by psychiatry; and two, those affected by it are not the only individuals to be affected from the condition. A variety of psychotherapeutic techniques have been used to treat depersonalization disorder, such as cognitive behavioral therapy. Clinical pharmacotherapy research continues to explore a number of possible options, including selective serotonin reuptake inhibitors, tricyclic antidepressants, anticonvulsants, and opioid antagonists. Cognitive behavior therapy An open study of cognitive behavior therapy has aimed to help patients reinterpret their symptoms in a nonthreatening way, leading to an improvement on several standardized measures. A standardized treatment for DPD based on cognitive behavioral principles was published in The Netherlands in 2011. Neither antidepressants nor antipsychotics have been found to be useful, Additionally antipsychotics can worsen symptoms of depersonalisation. To date, no clinical trials have studied the effectiveness of benzodiazepines. Tentative evidence supports naloxone and naltrexone. A combination of an SSRI and a benzodiazepine has been proposed to be useful for DPD patients with anxiety. Modafinil used alone has been reported to be effective in a subgroup of individuals with depersonalization disorder (those who have attentional impairments, under-arousal and hypersomnia). However, clinical trials have not been conducted. Men and women are diagnosed in equal numbers with depersonalization disorder. A 1991 study on a sample from Winnipeg, Manitoba estimated the prevalence of depersonalization disorder at 2.4% of the population. A 2008 review of several studies estimated the prevalence between 0.8% and 1.9%. This disorder is episodic in about one-third of individuals, with each episode lasting from hours to months at a time. Depersonalization can begin episodically, and later become continuous at constant or varying intensity. Onset is typically during the teenage years or early 20s, although some report being depersonalized as long as they can remember, and others report a later onset. The onset can be acute or insidious. With acute onset, some individuals remember the exact time and place of their first experience of depersonalization. This may follow a prolonged period of severe stress, a traumatic event, an episode of another mental illness, or drug use. Insidious onset may reach back as far as can be remembered, or it may begin with smaller episodes of lesser severity that become gradually stronger. Patients with drug-induced depersonalization do not appear to be a clinically separate group from those with a non-drug precipitant. Relation to other psychiatric disorders Depersonalization exists as both a primary and secondary phenomenon, although making a clinical distinction appears easy but is not absolute. The most common comorbid disorders are depression and anxiety, although cases of depersonalization disorder without symptoms of either do exist. Comorbid obsessive and compulsive behaviours may exist as attempts to deal with depersonalization, such as checking whether symptoms have changed and avoiding behavioural and cognitive factors that exacerbate symptoms. Researchers at the Institute of Psychiatry in London, England suggest depersonalization disorder be placed with anxiety and mood disorders, as in the ICD-10, instead of with dissociative disorders as in the DSM-IV-TR. The word depersonalization itself was first used by Henri Frédéric Amiel in The Journal Intime. The 8 July 1880 entry reads: "I find myself regarding existence as though from beyond the tomb, from another world; all is strange to me; I am, as it were, outside my own body and individuality; I am depersonalized, detached, cut adrift. Is this madness?" Depersonalization was first used as a clinical term by Ludovic Dugas in 1898 to refer to "a state in which there is the feeling or sensation that thoughts and acts elude the self and become strange; there is an alienation of personality – in other words a depersonalization". This description refers to personalization as a psychical synthesis of attribution of states to the self. Early theories of the cause of depersonalization focused on sensory impairment. Maurice Krishaber proposed depersonalization was the result of pathological changes to the body's sensory modalities which lead to experiences of "self-strangeness" and the description of one patient who "feels that he is no longer himself". One of Carl Wernicke's students suggested all sensations were composed of a sensory component and a related muscular sensation that came from the movement itself and served to guide the sensory apparatus to the stimulus. In depersonalized patients these two components were not synchronized, and the myogenic sensation failed to reach consciousness. The sensory hypothesis was challenged by others who suggested that patient complaints were being taken too literally and that some descriptions were metaphors – attempts to describe experiences that are difficult to articulate in words. Pierre Janet approached the theory by pointing out his patients with clear sensory pathology did not complain of symptoms of unreality, and that those who have depersonalization were normal from a sensory viewpoint. Psychodynamic theory formed the basis for the conceptualization of dissociation as a defense mechanism. Within this framework, depersonalization is understood as a defense against a variety of negative feelings, conflicts, or experiences. Sigmund Freud himself experienced fleeting derealization when visiting the Acropolis in person; having read about it for years and knowing it existed, seeing the real thing was overwhelming and proved difficult for him to perceive it as real. Freudian theory is the basis for the description of depersonalization as a dissociative reaction, placed within the category of psychoneurotic disorders, in the first two editions of the Diagnostic and Statistical Manual of Mental Disorders. Some argue that because depersonalization and derealization are both impairments to one’s ability to perceive reality, they are merely two facets of the same disorder. Depersonalization also differs from delusion in the sense that the patient is able to differentiate between reality and the symptoms they may experience. The ability to sense that something is unreal is maintained when experiencing symptoms of the disorder. The problem with properly defining depersonalization also lies within the understanding of what reality actually is. In order to comprehend the nature of reality we must incorporate all the subjective experiences throughout and thus the problem of obtaining an objective definition is brought about again. Society and culture Depersonalization disorder has appeared in a variety of media. The director of the autobiographical documentary Tarnation, Jonathan Caouette, had depersonalization disorder. The screenwriter for the 2007 film Numb had depersonalization disorder, as does the film's protagonist played by Matthew Perry. Norwegian painter Edvard Munch's famous masterpiece The Scream may have been inspired by depersonalization disorder. In Glen Hirshberg's novel The Snowman's Children, main female plot characters throughout the book had a condition that is revealed to be depersonalization disorder. Suzanne Segal had an episode in her 20s that was diagnosed by several psychologists as depersonalization disorder, though Segal herself interpreted it through the lens of Buddhism as a spiritual experience. The song "Is Happiness Just a Word?" by hip hop artist Vinnie Paz describes his struggle with depersonalization disorder. Adam Duritz, of the band Counting Crows, has often spoken about his diagnosis of depersonalization disorder. - "Depersonalization derealization disorder: Epidemiology, pathogenesis, clinical manifestations, course, and diagnosis". - Simeon D (2004). "Depersonalisation Disorder: A Contemporary Overview". CNS Drugs. 18 (6): 343–354. doi:10.2165/00023210-200418060-00002. PMID 15089102. - Simeon, Daphne. "Depersonalisation Disorder: A Contemporary Overview". Adis International. 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PMID 3783140. - Simeon and Abugel p. 73-4 - Saxe GN, van der Kolk BA, Berkowitz R, et al. (July 1993). "Dissociative disorders in psychiatric inpatients". Am J Psychiatry. 150 (7): 1037–42. doi:10.1176/ajp.150.7.1037. PMID 8317573. - Sugiura, Miyuki; Hirosawa, Masataka; Tanaka, Sumio; Nishi, Yasunobu; Yamada, Yasuyuki; Mizuno, Motoki (1 June 2009). "Reliability and validity of a Japanese version of the Cambridge depersonalization scale as a screening instrument for depersonalization disorder". Psychiatry and Clinical Neurosciences. 63 (3): 314–321. doi:10.1111/j.1440-1819.2009.01939.x. PMID 19566762. - Medford N, Sierra M, Baker D, David AS (2005). "Understanding and treating depersonalization disorder". Advances in Psychiatric Treatment. 11 (5): 92–100. doi:10.1192/apt.11.2.92. - Hunter EC, Baker D, Phillips ML, Sierra M, David AS (September 2005). "Cognitive-behaviour therapy for depersonalisation disorder: an open study". Behav Res Ther. 43 (9): 1121–30. doi:10.1016/j.brat.2004.08.003. PMID 16005701. - Bar, E., & Minnen van, A. (2011). Protocollaire behandeling van de depersonalisatiestoornis. In: G.P.J. Keijsers, A.van Minnen, & C.A.L. Hoogduin (red.). Protocollaire behandelingen voor volwassenen met psychische klachten. Arnhem, Boom Cure & Care publishers. - Sierra, M (January 2008). "Depersonalization disorder: pharmacological approaches.". Expert Review of Neurotherapeutics. 8 (1): 19–26. doi:10.1586/1473722.214.171.124. PMID 18088198. - Sierra M (2008). "Depersonalization disorder: pharmacological approaches". Expert Rev Neurother. 8 (1): 19–26. doi:10.1586/14737126.96.36.199. PMID 18088198. - Mauricio Sierra (13 August 2009). Depersonalization: A New Look at a Neglected Syndrome. Cambridge, UK: Cambridge University Press. p. 120. ISBN 0-521-87498-X. - Ross CA (1991). "Epidemiology of multiple personality disorder and dissociation". Psychiatric Clinics of North America. 14 (3): 503–17. PMID 1946021. - Medford N, Baker D, Hunter E, et al. (December 2003). "Chronic depersonalization following illicit drug use: a controlled analysis of 40 cases". Addiction. 98 (12): 1731–6. doi:10.1111/j.1360-0443.2003.00548.x. PMID 14651505. - Henri Frédéric Amiel's The Journal Intime Retrieved June 2, 2007 - Berrios GE, Sierra M (June 1997). "Depersonalization: a conceptual history". Hist Psychiatry. 8 (30 Pt 2): 213–29. doi:10.1177/0957154X9700803002. PMID 11619439. - Mayer-Gross W. (1935). "On depersonalization." British Journal of Medicine and Psychology (15)103–126. - Simeon and Abugel p. 12 & 58 - Sogomy, Varga (June 2012). "Depersonalization and the Sense of Realness". Philosophy, Psychiatry, & Psychology. 19 (2). - Simeon, D; Abugel J (2006). "The Blow of the Void: Depersonalization in Literature and Philosophy". Feeling unreal: depersonalization disorder and the loss of the self. United States: Oxford University Press. pp. 127–58. ISBN 0-19-517022-9. - Hirshberg, Glen (2003). The Snowman's Children: A Novel. New York, NY: Carroll & Graf. ISBN 0-7867-1253-8. - Suzanne Segal (1996). Collision With the Infinite: A Life Beyond the Personal Self. Blue Dove Press. ISBN 1-884997-27-9. - "A Lesson in Humility from Adam Duritz". Men's Health. September 30, 2014. Retrieved May 30, 2016.	2	38	9	0	4	4	0.960393	17	7,602
What is ICD-9 ICD – International Classification of Diseases. 9 – Ninth Revision. This classification was developed by World Health Organization. In this classification for each known disease assigned unique code number. Majority of the U.S. healthcare systems use the ICD-9 codes for making diagnosis and settling payments. The coding is standard around the world, however, in the 2010’s many countries went on to use ICD-10 and then ICD – 11 systems, which include more information. ICD-9 for Psoriasis Psoriasis falls under “Other inflammatory conditions of skin and subcutaneous tissue”, which is between codes 690 and 698. The disease itself has a code 696 (Psoriasis and similar disorders), which is divided into the sub-codes: \|696.8\|\|Other psoriasis and similar disorders\| ICD-10 for Psoriasis As opposed to ICD – 9, which has only point 696.1 for psoriasis and similar disorders, ICD – 10 has an L40 subdivision to describe the various types of psoriasis. \|L40.1\|\|Generalized pustular psoriasis\| \|L40.3\|\|Pustulosis palmaris et plantaris\| \|L40.51\|\|Distal interphalangeal psoriatic arthropathy\| \|L40.52\|\|Psoriatic arthritis mutilans\| \|L40.54\|\|Psoriatic juvenile arthropathy\| \|L40.59\|\|Other psoriatic arthropathy\| ICD-11 is currently in the draft stage.	4	5	0	0	0	4	0.827561	4	345
Topic: W2 A 2 Assignment Assignment 2: Case Study Analysis and Care Plan Creation Click here to download and analyze the case study for this week. Create a wholistic care plan for disease prevention, health promotion, and acute care of the patient in the clinical case. Your care plan should be based on current evidence and nursing standards of care. Visit the online library and research for current scholarly evidence (no older than 5 years) to support your nursing actions. In addition, consider visiting government sites such as the CDC, WHO, AHRQ, Healthy People 2020. Provide a detailed scientific rationale justifying the inclusion of this evidence in your plan. Next determine the ICD-10 classification (diagnoses). The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-10-CM) is the official system used in the United States to classify and assign codes to health conditions and related information. •Search term page to identify the codes applicable to the care plan. https://www.cms.gov/Medicare/Coding/ICD10/index.html •This link will lead to an excel version of the latest codes: https://www.cms.gov/Medicare/Coding/ICD10ProviderDiagnosticCodes/codes.html Click here to download the care plan template to help you design a holistic patient care plan. The care plan example provided here is meant only as a frame of reference for you to build your care plan. You are expected to develop a comprehensive care plan based on your assessment, diagnosis, and advanced nursing interventions. Reflect on what you have learned about care plans through independent research and peer discussions and incorporate the knowledge that you have gained into your patient’s care plan. Your care plan should be formatted as a Microsoft Word document. Follow the current APA edition style. Your paper should be 2 to 4 pages double-spaced and in 12pt font. Name your document: SU_NSG6001_W2A2_LastName_FirstInitial.doc. Submit your document to the W2 Assignment 2 Dropbox by Saturday, September 26, 2015. Care plan demonstrated involvement of the client in the process of recognition, planning, and resolution of the problem. Care plan included effective nursing interventions that are customized for the client and appropriate to the goal. Care plan included diagnostic work-up, medications, conservative measures, and follow-up plan. Care plan provided rationale for choosing a particular treatment modality. Care plan demonstrated logical diagnosis that was substantiated with relevant evidence. Care plan focused on patient education and maintained a fine balance between major and minor health issues of the patient. Care plan included nursing interventions that are specific, appropriate, and free of essential omissions. Used APA standards consistently and accurately. THIS IS THE CASE OF STUDY FOR THIS WEEK Pulmonology Case Study A 65-year-old Caucasian female presents with a chief complaint of cough for two weeks. She has been complaining of dry cough since the past two weeks and low grade fever that started two days ago, and was as high as 101 orally. She has had a decreased appetite but no nausea and vomiting. The cough occurs during the night and she needs to sit up in a chair to be able to breathe easier. The cough is mainly dry, rarely productive. She had been prescribed inhalers in the past; they have been helpful but she does not use them on a routine basis. She has been prescribed antibiotics in the past as well and that seems to help when she is acutely ill. She has been suffering from shortness of breath for the past two weeks following any kind of activity mainly because of the dry cough. She thinks it’s possible that there’s some problem with her “heart.” She is also complaining of slight sore throat, especially in the morning and feels she may have lung cancer. The patient’s symptoms have been worsening over the past two days. She has had similar episodes in the past. The last was three months ago when she had to go to the emergency room and they told her that she needed to be hospitalized. She declined hospitalization at that time and was treated and released. She says they gave her antibiotics and an inhaler before discharging her. She mentioned that though it took some time to feel better, there was gradual improvement in her condition following that treatment. According to her, this is the worst episode that she can remember. She’s very concerned today that she could have pneumonia and might require hospitalization. She is seeking medical attention today because of the fever and prolonged nature of her illness. Though she has been treated for this problem in the past with antibiotics and inhalers, she has not been hospitalized. The patient had a chest investigation the last time she had this problem. She states that she did not have pneumonia but did have “emphysema.” The healthcare professionals wanted to do pulmonary function tests, but she declined. X-ray results: Hyperinflation of both lungs with an increased AP diameter. There is evidence of emphysema. . She states that she had asthma as a child and is a cigarette smoker. She also had a hysterectomy way back in 1970s. Besides these, she has no known chronic medical problems. Shortness of breath with activity. No diaphoresis. She has had a fever. No nausea and vomiting. Denies chest pressure sensation with physical activity. No palpitations. The patient does not take any prescription medicines. She takes occasional over-the- counter Tylenol for pain. Tylenol 650 mg, 2 PO as needed. She is allergic to sulfa drugs that cause a rash. The patient has been widowed for 20 years. She is receiving an annual pension of $40,000.00 and has some money that she has saved in the bank. She has a high school diploma and owns her house. Though she has little disposable income, her finances are essentially stable. She has little knowledge of community resources that are at her disposal. She has a primary care provider, whom she sees three to four times every year for a physical examination. The physician is very busy and does not spend much time with her. She has insurance but it does not cover all her prescription medications. She relies on a lot on samples. She has two grown-up daughters who live in the nearby community. They are both in their forties and are alive and well. The patient would like her daughters to be more involved in her life, but she is not sure how to approach them about this. The patient’s perception of self-efficacy has been declining over the past ten years. She feels that she could be feeling depressed because she does not get out of the house very often and this depression is only getting worse with each passing year. The patient has very low level of day-to-day stress. However, she realizes that her depressive symptoms may be causing some of her physical symptoms. She goes to church and has some contacts there. She sees her daughters once a month. These people are her support system, but she has no one to talk to on a routine basis. • Diet habits She has a healthy diet and her dietary intake is adequate. The patient has positive health beliefs and knows that she should be doing more to maintain a healthy lifestyle. She does not get adequate exercise because of her shortness of breath. She enjoys visiting her physician. Smoking: She has smoked one pack per day for 40 years. Alcohol: She denies alcohol use Substance Use: She denies any street drug use She has always been a hairdresser; is retired now. She goes to church and occasionally attends some of their functions. Her hobbies include sewing. She is from the United States and lives in a suburban setting. Crime rate in her locality is low with easy access to public transportation. There are a variety of community groups, but she is not aware of these resources. Her two older sisters are alive and well, one with osteoporosis and one with breast cancer. Her 75-year-old sister was diagnosed with osteoporosis at the age of 55. Her 72- year-old sister was diagnosed with breast cancer at 60 years of age. Vital Signs: BP: 130/72 left arm sitting regular cuff; T: 101 po; P: 100 and regular; R: 20, non-labored; Wt: 130#; Ht: 55”. HEENT: White material on the buccal mucosa; does not wipe off with tongue blade. Lymph Nodes: None Lungs: Decreased breath sounds, dull to percussion right lower lobe. End expiratory wheeze in right lower lobe. No rales or rhonchi. Increased anterior-posterior diameter to chest wall. Heart: RRR without murmur Carotids: No bruits Abdomen: Benign Rectum: Not examined Genital/Pelvic: Not examined Extremities, Including Pulses: 2+ pulses throughout, no edema Neurologic: Not examined LAB RESULTS/RADIOLOGICAL STUDIES/EKG INTERPRETATION CBC- WBCs 15, 000 with + left shift Pulse oximeter reading: SAO2: 98% CXR – Same as X-ray Normal sinus rhythm THIS IS THE EXAMPLE of my first week THAT YOU HAVE TO FOLLOW TO DO THIS Cardiology Case Study ADVANCED PRACTICE NURSING CASE STUDY WEEK ONE 2 Patient Initials: A.H. Age: 52 Sex: M A.H. is being seen here today for a follow up visit following stent placement. Patient had stent placed on previous admission and is concern that he will have continued episodes of angina, even with having stents placed. Patient is seeking information on his risk factors associated with angina (Week 1: Cardiology Clinical Case, 2015). Patient is asymptomatic and has no new complaints at this time. Patient is being seen for follow up treatment status post stent placement. Patient is seeking education on his risk factors for angina following stent placement (Week 1: Cardiology Clinical Case, History of Present Illness Patient presented to the emergency department with four hour of chest pain. The patient when presented complained of shortness of breath with exertion and he was diaphoretic. The patient states that the pain in his chest was crushing, substernal, and radiated to his neck and jaw. Patient had these episodes for four days and was fearful to go to the hospital to seek help. Patient stated that the pain was worse today and he could not resolve with rest. Patient states that he has been having similar episodes for over six months but he just thought the episodes were due to him being out of shape. Patient stated that he normally could resolve his angina episodes by rest prior to his visit to the emergency room. The patient was admitted to the hospital, transferred to the cardiac floor, and a catheterization was scheduled. Prior to transfer the patient symptoms were ADVANCED PRACTICE NURSING CASE STUDY WEEK ONE 3 relieved by the emergency room with medication. The patient was hospitalized for four days and had stents placed during this admission. The patient is seeking advice regarding his concern of future angina attacks (Week 1: Cardiology Clinical Case, 2015). Past Medical History The patient has been diagnosed with hypertension and high cholesterol; however, he is not compliant with his medications, and he stopped taking them. The only surgery that the patient has had in the past before the stent placement was a cholecystectomy and that was over ten years ago. The patient denies any allergies and the only other hospitalization was for his cholecystectomy. The patient had an EKG on file at his PCP office from when he was prescribed his hypertensive medications. The patient did have his cholesterol level periodically checked. The patient was prescribed daily medications on discharge from the hospital, and has been complaint with his discharge regimen, and the medication list is as follows: ? Tenormin XL 50 mg daily ? Lipitor 10 mg daily ? Glucophage 500 mg BID ? Baby Aspirin 81 mg daily (Week 1: Cardiology Clinical Case, 2015) Significant Family History The patient has two older brothers that are currently being treated for hypertension and type two diabetes. The brothers were diagnosed in their forties with these disorders. Both the patient parents are deceased. The patient father dies from heart ADVANCED PRACTICE NURSING CASE STUDY WEEK ONE 4 disease and his mother dies from breast cancer (Week 1: Cardiology Clinical Case, Social and Personal History The patient is a carpenter and makes about 50,000.00 dollars a year. He is a high graduate. The patient lives with his wife in a one bedroom apartment in the inner city that has a high crime rating. They live pay check to pay check and his spouse is disabled. They have three grown children that do not live in the area. He does not participate in any physical activity. They have limited community involvement and do not have any family in the area. He lacks social and emotional support. The patient has limited health insurance coverage and uses the local clinic as his PCP. The patient prescriptions are not covered by his current health care plan (Week 1: Cardiology Clinical Case, 2015). The patient eats one large meal a day after work and does not eat breakfast. The patient when he does eat lunch consist of fast food. The patient eats limited fruits and vegetables and mostly eats pasta and meat when he meals at home. The patient smokes a pack a day for over thirty years. The patient does not drink and does not use any illegal drugs. The patient does not have any hobbies outside the home and will read when he at home. The patient states that the exercise that he receives as a carpenter is enough physical exercise for him to be healthy and feels like he got enough exercise when he was younger (Week 1: Cardiology Clinical Case, 2015). Client’s Support System The patient is married to a disabled spouse from uncontrolled diabetes type two. He lacks any family support and is isolated from the community. The patient uses the ADVANCED PRACTICE NURSING CASE STUDY WEEK ONE 5 local clinic as a primary care source, so he never sees the same practitioner (Week 1: Cardiology Clinical Case, 2015). Behavioral or Nonverbal Messages The patient has anxiety regarding returning to work. The patient is scared that he will be unable to care for his spouse, due to his recent illnesses. The patient has high stressed levels and is worried over his finances. The patient has a strong family sense and believes that as a real man he should be able to care for his family and should be strong enough not to suffer from any diseases. The patient suffers from depression. He is dealing with his depression by over eating and sleeping excessively (Week 1: Cardiology Clinical Client Awareness of Abilities, Disease Process, and Health Care Needs Patient is fearful of being able to continue to financially take care of his spouse and himself. The patient is seeking advice on the risk factors for angina. The patient needs education on the causes of angina and his risk of heart disease. The patient also needs assistance with his medications due to lack of insurance coverage for medication. The patient has limited knowledge on his disease process and the reason for stent placement (Week 1: Cardiology Clinical Case, 2015). The patient’s objective data is as follows: ADVANCED PRACTICE NURSING CASE STUDY WEEK ONE 6 ? WT- 220 POUNDS ? HT- 70 INCHES ? BMI- 31.6 (Calculate Your Body Mass Index, n.d.) Physical Assessment Findings: ? LYMPH NODES- None ? LUNGS- Decreased breath sounds throughout no adventitious sounds ? HEART- RRR without murmurs noted ? CAROTIDS- Right Bruit ? ABDOMEN- Obesity ? RECTUM- Not Examined ? GENTITAL/PELVIC – NA ? EXTREMITIES WITH PULSES- Decreased pedal pulses BL with lower leg edema from ankle to mid-calf ? NEUROLOGIC- Not Examined ? EKG- No changes from baseline ? TOTAL CHOLESTEROL- 210 ADVANCED PRACTICE NURSING CASE STUDY WEEK ONE 7 ? TRIGLYCERIDES- 250 ? FASTING BLOOD SUGAR- 140 ? CXR- Hyperinflation of the lungs without infiltrates noted ? EKG- No change noted from previous Client’s Support System: Disabled Spouse Client’s Locus of Control and Readiness to Learn: Patient is showing his wiliness to learn by coming to follow up appointment and seeking advice on risk factors for angina. He has been following his discharge planning and taking his medications as prescribed (Week 1: Cardiology Clinical Case, 2015). ICD-9 Diagnoses/Client Problems ? 413.9- OTHER AND UNSPECIFIED ANGINA PECTORIS ? 401.9- UNSPECIFIED ESSENTIAL HYPERTENSION ? 272.4- OTHER AND UNSPECIFIED HYPERLIPIDEMA ? 250.02- DIABETES MELLITUS WITHOUT MENTION OF COMPLICATION, TYPE II OR UNSPECIFIED TYPE, UNCONTROLLED ? 278.00- OBESITY UNSPECIFIED ? V79.0- SCREENING FOR DEPRESSION ? 309.28- ADJUSTMENT DOSORDER WITH MIXED ANXIETY AND ? V15.82- PERSONAL HISTORY OF TOBACCO USE ? 786.59- OTHER CHEST PAIN ADVANCED PRACTICE NURSING CASE STUDY WEEK ONE 8 Advanced Practice Nursing Intervention Plan Coronary artery disease is the primary cause of death for both men and women in the United States. CAD includes acute MI, angina pectoris, atherosclerotic cardiovascular disease, and any chronic ischemic heart disease. There are modifiable and nonmodifiable risk factors that lead to heart disease. The factors that the patient cannot control is his family history, his age, and gender. The modifiable risk factors that the patient has control over is his smoking, lack of physical exercise, diet, obesity, and stress level (Buttaro, Terry, Trybulski, Bailey, & Cook, 2013 pg. 518-519). Stable angina is precipitated by exertion and is typically relieved by rest. The demand or reduction in myocardial oxygen supply are the factors that cause coronary ischemia. There is three factors that determine the amount of oxygen needed; the heart rate, systemic blood pressure, and left ventricular wall tension. The heart rate and blood pressure influence the oxygen requirements because both determine the myocardial workload. Activities and increased metabolic demands that increase the workload of the heart increases that oxygen requirements and causes angina and ischemia (Buttaro, Terry, Trybulski, Bailey, & Cook, 2013 pg. 520). A.H. condition is complicated because he has comorbid diseases that will require him to be followed by a cardiologist. The amount of follow up visits will be determined by the cardiologist. The clinic that the patient uses as primary care will follow the cardiologist recommendations. The patient will require management of his disease processes and medications which the clinic is able to provide. A.H. will be provided with nitroglycerin tablets and education will be provided on the use of these tablets. On the ADVANCED PRACTICE NURSING CASE STUDY WEEK ONE 9 visit the patient will be asked about the frequency of his episodes, the severity of pain, and if he is using his nitro tablets. The patient will receive education on angina and the warning signs of a heart attack (Buttaro, Terry, Trybulski, Bailey, & Cook, 2013). The patient will continue with his prescribed medications because the use of calcium channel blockers, beta blockers, and nitroglycerin help reduce the episodes of chest pain (Alaeddini, 2014). This assigned treatment plan will also benefit the patient is his management of hypertension. The patient will be provided with information and help from the CDC website on smoking cessation. The patient primary care physician will focus on diet, exercise, smoking, and management of his present illnesses. The patient will receive lab work at his appointment to assess cholesterol levels, and diabetes control (Alaeddini, 2014). The patient was provided with resources in his community that will help him with his medication cost, diet planning, and exercise (Buttaro, Terry, Trybulski, ADVANCED PRACTICE NURSING CASE STUDY WEEK ONE 10 Alaeddini, J. (2014, March 27). Angina Pectoris Follow-up. Retrieved from Buttaro, Terry, JoAnn Trybulski, Patricia Bailey, and Joanne Sandberg-Cook. Primary Care, 4th Edition. Mosby, 2013. VitalBook file. Retrieved from Calculate Your Body Mass Index. (n.d.). Retrieved from ICD-9 Code Lookup. (n.d.). Retrieved from https://www.cms.gov/medicare-coverage- Week 1: Cardiology Clinical Case. (2015). Retrieved from https://myeclassonline.com/re/DotNextLaunch.asp?courseidPLEASE CALL ME IF YOU DON’T UNDERSTOOD SOME THING	2	26	0	0	0	2	0.298527	2	4,712
ICD-9-CM is the official system of assigning codes to diagnoses and procedures associated with hospital utilization in the United States. The ICD-9 was used to code and classify mortality data from death certificates until 1999, when use of ICD-10 for mortality coding started. What is the difference between ICD-9 codes and ICD-10? Code set differences ICD-9-CM codes are very different than ICD-10-CM/PCS code sets: There are nearly 19 times as many procedure codes in ICD-10-PCS than in ICD-9-CM volume 3. There are nearly 5 times as many diagnosis codes in ICD-10-CM than in ICD-9-CM. ICD-10 has alphanumeric categories instead of numeric ones. Why did ICD-9 change to ICD-10? ICD-9 follows an outdated 1970’s medical coding system which fails to capture detailed health care data and is inconsistent with current medical practice. By transitioning to ICD-10, providers will have: Improved operational processes by classifying detail within codes to accurately process payments and reimbursements. What is the meaning of ICD-9? The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) is the U.S. health system’s adaptation of international ICD-9 standard list of six-character alphanumeric codes to describe diagnoses. What does ICD-9 code mean in medical terms? The International Classification of Diseases Clinical Modification, 9th Revision (ICD-9 CM) is a list of codes intended for the classification of diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or disease. When did we stop using ICD-9 codes? No updates have been made to ICD-9 since October 1, 2013, as the code set is no longer being maintained. What are the differences between ICD-9 codes and CPT codes? In a concise statement, ICD-9 is the code used to describe the condition or disease being treated, also known as the diagnosis. CPT is the code used to describe the treatment and diagnostic services provided for that diagnosis. What is the ICD code for Covid? For individuals with MIS and COVID-19, assign code U07. 1, COVID-19, as the principal/first-listed diagnosis and assign code M35. 81 as an additional diagnosis. What is an ICD-10 diagnosis code? Used for medical claim reporting in all healthcare settings, ICD-10-CM is a standardized classification system of diagnosis codes that represent conditions and diseases, related health problems, abnormal findings, signs and symptoms, injuries, external causes of injuries and diseases, and social circumstances.	4	3	0	0	0	1	0.580482	1	598
First of all, most medical offices consist of two distinct workplace areas: the front office and the back office. Front office medical assistants perform administrative and clerical duties. They tend to carry out tasks related to reception, medical records, files, insurance billing, computerized accounting, answering telephones and emails, and appointment scheduling, among the array of duties and responsibilities. Back office medical assistants perform hands-on patient care. Front office medical assistants specifically work in the front office section of the clinic or medical office. They are often entrusted with the responsibility of doing medical billing and coding. The medical bill is generated based on the diagnoses and procedures that had been rendered during the patient’s visit to the clinic, doctors office, hospital or other type of healthcare agency. If the patient is insured, a claim is sent to the patient’s medical insurance company for reimbursement. Each medical diagnosis has an ICD code. ICD stands for the International Classification of Diseases. ICD-10 is a clinical system that went into effect in late 2015 to replace the ICD-9. The difference between the ICD-9 and the ICD-10 is the reality that ICD-10 codes offer substantially more classification options when compared with those found in the ICD-9. Without further ado, some common ICD-10 codes and the corresponding diagnoses are listed below: - Type 2 diabetes mellitus without complications: E11.9 - Alzheimer’s disease, unspecified: G30.9 - Benign essential hypertension: I10 - Urinary tract infection, site not specified: N39.0 - Pregnancy care for patient with recurrent pregnancy loss: O26.2 - Morbid (severe) obesity due to excess calories: E66.01 - Underweight: R63.6 - Major depressive disorder, recurrent, mild: F33.0 - Other specified anxiety disorders: F41.8 - Encounter for routine child health examination: Z00.12 - Encounter for routine gynecological examination: Z01.41	4	2	0	0	0	2	0.637299	2	424
A desmoid tumor is an abnormal growth that arises from connective tissue, which is the tissue that provides strength and flexibility to structures such as bones, ligaments, and muscles. Typically, a single tumor develops, although some people have multiple tumors. The tumors can occur anywhere in the body. Tumors that form in the abdominal wall are called abdominal desmoid tumors; those that arise from the tissue that connects the abdominal organs are called intra-abdominal desmoid tumors; and tumors found in other regions of the body are called extra-abdominal desmoid tumors. Extra-abdominal tumors occur most often in the shoulders, upper arms, and upper legs. Desmoid tumors are fibrous, much like scar tissue. They are generally not considered cancerous (malignant) because they do not spread to other parts of the body (metastasize); however, they can aggressively invade the surrounding tissue and can be very difficult to remove surgically. These tumors often recur, even after apparently complete removal. The most common symptom of desmoid tumors is pain. Other signs and symptoms, which are often caused by growth of the tumor into surrounding tissue, vary based on the size and location of the tumor. Intra-abdominal desmoid tumors can block the bowel, causing constipation. Extra-abdominal desmoid tumors can restrict the movement of affected joints and cause limping or difficulty moving the arms or legs. Desmoid tumors occur frequently in people with an inherited form of colon cancer called familial adenomatous polyposis (FAP). These individuals typically develop intra-abdominal desmoid tumors in addition to abnormal growths (called polyps) and cancerous tumors in the colon. Desmoid tumors that are not part of an inherited condition are described as sporadic. Desmoid tumors are rare, affecting an estimated 1 to 2 per 500,000 people worldwide. In the United States, 900 to 1,500 new cases are diagnosed per year. Sporadic desmoid tumors are more common than those associated with familial adenomatous polyposis. Mutations in the CTNNB1 gene or the APC gene cause desmoid tumors. CTNNB1 gene mutations account for around 85 percent of sporadic desmoid tumors. APC gene mutations cause desmoid tumors associated with familial adenomatous polyposis as well as 10 to 15 percent of sporadic desmoid tumors. Both genes are involved in an important cell signaling pathway that controls the growth and division (proliferation) of cells and the process by which cells mature to carry out specific functions (differentiation). The CTNNB1 gene provides instructions for making a protein called beta-catenin. As part of the cell-signaling pathway, beta-catenin interacts with other proteins to control the activity (expression) of particular genes, which helps promote cell proliferation and differentiation. CTNNB1 gene mutations lead to an abnormally stable beta-catenin protein that is not broken down when it is no longer needed. The protein accumulates in cells, where it continues to function in an uncontrolled way. The protein produced from the APC gene helps regulate levels of beta-catenin in the cell. When beta-catenin is no longer needed, the APC protein attaches (binds) to it, which signals for it to be broken down. Mutations in the APC gene that cause desmoid tumors lead to a short APC protein that is unable to interact with beta-catenin. As a result, beta-catenin is not broken down and, instead, accumulates in cells. Excess beta-catenin, whether caused by CTNNB1 or APC gene mutations, promotes uncontrolled growth and division of cells, allowing the formation of desmoid tumors. Most desmoid tumors are sporadic and are not inherited. Sporadic tumors result from gene mutations that occur during a person's lifetime, called somatic mutations. A somatic mutation in one copy of the gene is sufficient to cause the disorder. Somatic mutations in either the CTNNB1 or the APC gene can cause sporadic desmoid tumors. An inherited mutation in one copy of the APC gene causes familial adenomatous polyposis and predisposes affected individuals to develop desmoid tumors. The desmoid tumors occur when a somatic mutation occurs in the second copy of the APC gene. In these cases, the condition is sometimes called hereditary desmoid disease. Other Names for This Condition - Aggressive fibromatosis - Deep fibromatosis - Desmoid fibromatosis - Familial infiltrative fibromatosis - Hereditary desmoid disease - Musculoaponeurotic fibromatosis Additional Information & Resources Genetic Testing Information Genetic and Rare Diseases Information Center Research Studies from ClinicalTrials.gov Catalog of Genes and Diseases from OMIM Scientific Articles on PubMed - Alman BA, Li C, Pajerski ME, Diaz-Cano S, Wolfe HJ. Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors). Am J Pathol. 1997 Aug;151(2):329-34. Citation on PubMed or Free article on PubMed Central - Escobar C, Munker R, Thomas JO, Li BD, Burton GV. Update on desmoid tumors. Ann Oncol. 2012 Mar;23(3):562-569. doi: 10.1093/annonc/mdr386. Epub 2011 Aug 22. Review. Citation on PubMed - Huss S, Nehles J, Binot E, Wardelmann E, Mittler J, Kleine MA, Künstlinger H, Hartmann W, Hohenberger P, Merkelbach-Bruse S, Buettner R, Schildhaus HU. β-catenin (CTNNB1) mutations and clinicopathological features of mesenteric desmoid-type fibromatosis. Histopathology. 2013 Jan;62(2):294-304. doi: 10.1111/j.1365-2559.2012.04355.x. Epub 2012 Sep 28. Citation on PubMed - Kotiligam D, Lazar AJ, Pollock RE, Lev D. Desmoid tumor: a disease opportune for molecular insights. Histol Histopathol. 2008 Jan;23(1):117-26. doi: 10.14670/HH-23.117. Review. Citation on PubMed - Lips DJ, Barker N, Clevers H, Hennipman A. The role of APC and beta-catenin in the aetiology of aggressive fibromatosis (desmoid tumors). Eur J Surg Oncol. 2009 Jan;35(1):3-10. doi: 10.1016/j.ejso.2008.07.003. Epub 2008 Aug 21. Review. Citation on PubMed - Tejpar S, Nollet F, Li C, Wunder JS, Michils G, dal Cin P, Van Cutsem E, Bapat B, van Roy F, Cassiman JJ, Alman BA. Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor). Oncogene. 1999 Nov 11;18(47):6615-20. Citation on PubMed	2	10	2	0	0	0	0.550732	2	1,601
- Coronary artery disease Coronary artery disease Classification and external resources Micrograph of a coronary artery with the most common form of coronary artery disease (atherosclerosis) and marked luminal narrowing. Masson's trichrome. ICD-10 I20-I25 ICD-9 410-414, 429.2 eMedicine radio/192 MeSH D003324 Coronary artery disease (CAD; also atherosclerotic heart disease) is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the myocardium (the muscle of the heart) with oxygen and nutrients. It is sometimes also called coronary heart disease (CHD). Although CAD is the most common cause of CHD, it is not the only one. CAD is the leading cause of death worldwide. While the symptoms and signs of coronary artery disease are noted in the advanced state of disease, most individuals with coronary artery disease show no evidence of disease for decades as the disease progresses before the first onset of symptoms, often a "sudden" heart attack, finally arises. After decades of progression, some of these atheromatous plaques may rupture and (along with the activation of the blood clotting system) start limiting blood flow to the heart muscle. The disease is the most common cause of sudden death, and is also the most common reason for death of men and women over 20 years of age. According to present trends in the United States, half of healthy 40-year-old males will develop CAD in the future, and one in three healthy 40-year-old women. According to the Guinness Book of Records, Northern Ireland is the country with the most occurrences of CAD. By contrast, the Maasai of Africa have almost no heart disease. As the degree of coronary artery disease progresses, there may be near-complete obstruction of the lumen of the coronary artery, severely restricting the flow of oxygen-carrying blood to the myocardium. Individuals with this degree of coronary artery disease typically have suffered from one or more myocardial infarctions (heart attacks), and may have signs and symptoms of chronic coronary ischemia, including symptoms of angina at rest and flash pulmonary edema. A distinction should be made between myocardial ischemia and myocardial infarction. Ischemia means that the amount of blood supplied to the tissue is inadequate to supply the needs of the tissue. When the myocardium becomes ischemic, it does not function optimally. When large areas of the myocardium becomes ischemic, there can be impairment in the relaxation and contraction of the myocardium. If the blood flow to the tissue is improved, myocardial ischemia can be reversed. Infarction means that the tissue has undergone irreversible death due to lack of sufficient oxygen-rich blood. An individual may develop a rupture of an atheromatous plaque at any stage of the spectrum of coronary artery disease. The acute rupture of a plaque may lead to an acute myocardial infarction (heart attack). Limitation of blood flow to the heart causes ischemia (cell starvation secondary to a lack of oxygen) of the myocardial cells. Myocardial cells may die from lack of oxygen and this is called a myocardial infarction (commonly called a heart attack). It leads to heart muscle damage, heart muscle death and later myocardial scarring without heart muscle regrowth. Chronic high-grade stenosis of the coronary arteries can induce transient ischemia which leads to the induction of a ventricular arrhythmia, which may terminate into ventricular fibrillation leading to death. CAD is associated with smoking, diabetes, and hypertension. A family history of early CAD is one of the less important predictors of CAD. Most of the familial association of coronary artery disease are related to common dietary habits. Screening for CAD includes evaluating high-density and low-density lipoprotein (cholesterol) levels and triglyceride levels. Despite much press, most of the alternative risk factors including homocysteine, C-reactive protein (CRP), Lipoprotein (a), coronary calcium and more sophisticated lipid analysis have added little if any additional value to the conventional risk factors of smoking, diabetes and hypertension. Angina (chest pain) that occurs regularly with activity, after heavy meals, or at other predictable times is termed stable angina and is associated with high grade narrowings of the heart arteries. The symptoms of angina are often treated with betablocker therapy such as metoprolol or atenolol. Nitrate preparations such as nitroglycerin, which come in short-acting and long-acting forms are also effective in relieving symptoms but are not known to reduce the chances of future heart attacks. Many other more effective treatments, especially of the underlying atheromatous disease, have been developed. Angina that changes in intensity, character or frequency is termed unstable. Unstable angina may precede myocardial infarction, and requires urgent medical attention. It may be treated with oxygen, intravenous nitroglycerin, and aspirin. Interventional procedures such as angioplasty may be done. Characteristics of coronary artery disease Typically, coronary artery disease occurs when part of the smooth, elastic lining inside a coronary artery (the arteries that supply blood to the heart muscle) develops atherosclerosis. With atherosclerosis, the artery's lining becomes hardened, stiffened, and swollen with all sorts of "grunge" - including calcium deposits, fatty deposits, and abnormal inflammatory cells - to form a plaque. Deposits of calcium phosphates (hydroxyapatites) in the muscular layer of the blood vessels appear to play not only a significant role in stiffening arteries but also for the induction of an early phase of coronary arteriosclerosis. This can be seen in a so-called metatstatic mechanism of calcification as it occurs in chronic kidney disease and haemodialysis (Rainer Liedtke 2008). Although these patients suffer from a kidney dysfunction, almost fifty percent of them die due to coronary artery disease. Plaques can be thought of as large "pimples" that protrude into the channel of an artery, causing a partial obstruction to blood flow. Patients with coronary artery disease might have just one or two plaques, or might have dozens distributed throughout their coronary arteries. However, there is a term in medicine called “Cardiac Syndrome X”, which describes chest pain (Angina pectoris) and chest discomfort in people who do not show signs of blockages in the larger coronary arteries of their hearts when an angiogram (coronary angiogram) is being performed. No one knows exactly what causes “Cardiac Syndrome X” and it is unlikely to have a single cause. Today, we speculate that the major contributing factor to “Cardiac Syndrome X” is “microvascular dysfunction”.[who?] The term “microvascular” refers to very small blood vessels and, in this case, very small arteries (arterioles, capillaries) of the heart. Studies have also shown that people with “Cardiac Syndrome X” have enhanced pain perception, meaning they feel chest pain more intensely than the average person. The large majority of women have the garden variety of coronary artery disease. Rarely, women with “Cardiac Syndrome X” have typical anginal syndromes that are not associated with the presence of atherosclerotic plaques; that is, the localized blockages are absent. Scientists speculate that the blood vessels in these women are diffuse abnormal. Some have falsely claim that the entire lining of the artery becomes thickened throughout, making the plaques flush with the wall of the artery without any scientific proof. On cardiac catheterization their coronary arteries appear smooth-walled and normal, though they may look "small" in diameter. By the way: in general, female coronary arteries (like all arteries) are somewhat smaller than in males. “Cardiac Syndrome X” have never been shown to cause acute heart attacks (myocardial infarction) despite much speculation. The prognosis with syndrome-X coronary artery disease is also known to be better than with typical coronary artery disease, but this is not a benign condition since it can be quite disabling. It is not completely clear why women are more likely than men to suffer from "Syndrome X"; however, hormones and other risk factors unique to women may play a role. Women’s blood vessels are exposed to changing levels of oestrogen throughout their lives, first during regular menstrual cycles and later during and after menopause as oestrogen levels decline with age. Oestrogen affects how blood vessels narrow and widen and how they respond to injury, so changes in oestrogen levels mean changes in the reactivity of the blood vessels. Women’s vessels may be “programmed” for more changes than men’s vessels, which could increase the risk of having problems in the lining of the arteries (endothelial cells) and the smooth muscle cells in the walls of the arteries. The endothelial dysfunction is likely to be multifactorial in these patients and it is conceivable that risk factors such as hypertension, hypercholesterolemia, diabetes mellitus and smoking can contribute to its development. Most patients with Syndrome X are postmenopausal women and oestrogen deficiency has been therefore proposed as a pathogenic factor in female patients. In addition to changing hormone levels, there are several other risk conditions for blood vessel problems that are unique to women, such as preeclampsia (a problem associated with high blood pressure during pregnancy) and delivering a low-birth weight baby. Of course, despite these issues women, the female gender as a whole is protective against coronary artery disease. Cardiac Syndrome X often is a diagnosis of exclusion where the presence of typical chest pains is not accompanied by coronary artery narrowings on angiography. In considering Syndrome-X, it is important to understand that about 80% of chest pains have nothing to do with the heart. Therefore, the characteristics of typical chest pains must be carefully documented to avoid unnecessary labelling patients with heart disease: - Chest pain or Angina pectoris with physical stress; the pain may spread to the left arm or the neck, back, throat, or jaw. There might be present a numbness (paresthesia) or a loss of feeling in the arms, shoulders, or wrists - Coronary angiography demonstrates “normal” coronary arteries, i.e. no blockages or stenoses can be detected in the larger epicardial vessels - No inducible coronary artery spasm present during cardiac catheterization - Characteristic ischemic ECG changes during exercise testing - ST segment depression and angina in the presence of left ventricular wall perfusion abnormalities during thallium or other stress perfusion test - Consistent response to sublingual nitrates. - Postmenopausal or menopausal status The diagnosis of “Cardiac Syndrome X” - the rare coronary artery disease that is more common in women, as mentioned, an “exclusion” diagnosis. Therefore, usually the same tests are used as in any patient with the suspicion of coronary artery disease: - Baseline electrocardiography (ECG) - Exercise ECG – Stress test - Exercise radioisotope test (nuclear stress test, myocardial scintigraphy) - Echocardiography (including stress echocardiography) - Coronary angiography - Intravascular ultrasound - Magnetic resonance imaging (MRI) A variety of drugs are used in the attempt to treat the Syndrome-X coronary artery disease: nitrates, calcium channel antagonists, ACE-inhibitors, statins, imipramine (for analgesia), aminophylline, hormone replacement therapy (oestrogen), even electrical spinal cord stimulation are tried to overcome the symptomatology -all with mixed results. Quite often the quality of life for these women remains poor. While not enough is known about Syndrome-X coronary artery disease to list specific prevention techniques, adopting heart-healthy habits can be a good start. These include monitoring cholesterol and blood pressure levels, maintaining a low-fat diet, exercising regularly, quitting smoking, avoiding recreational drugs, and moderating alcohol intake. However, there might be a new option for women suffering from “Cardiac Syndrome X”: Protein based Angiogenesis. This new protein-based angiogenic therapy - using fibroblast growth factor 1 (FGF-1) - might be used as sole therapy as well as adjunct to bypass surgery – thus overcoming the limitations of conventional bypass surgery. Beyond drug therapy, interventional procedures, and coronary artery bypass grafting, angiogenesis now offers a new, specific and – so far as we know from three human clinical trials – effective treatment targeted for women’s coronary artery disease. The following are confirmed independent risk factors for the development of CAD: - Hypercholesterolemia (specifically, serum LDL concentrations) - Smoking - Hypertension (high systolic pressure seems to be most significant in this regard) - Hyperglycemia (due to diabetes mellitus or otherwise) - Type A Behavioural Patterns, TABP. Added in 1981 as an independent risk factor after a majority of research into the field discovered that TABP's were twice as likely to exhibit CAD as any other personality type. - Hemostatic Factors: High levels of fibrinogen and coagulation factor VII are associated with an increased risk of CAD. Factor VII levels are higher in individuals with a high intake of dietary fat. Decreased fibrinolytic activity has been reported in patients with coronary atherosclerosis. - Hereditary differences/genetic polymorphisms in such diverse aspects as lipoprotein structure and that of their associated receptors, enzymes of lipoprotein metabolism such as cholesteryl ester transfer protein (CETP) and hepatic lipase (HL), homocysteine processing/metabolism, etc. - High levels of Lipoprotein(a), a compound formed when LDL cholesterol combines with a substance known as Apoliprotein (a). Significant, but indirect risk factors include: - Lack of exercise - Consumption of alcohol - Diet rich in saturated fats - Diet low in antioxidants - Men over 60; Women over 65 - A recent study done in India (puducherry)shows its association with hemoglobin Risk factors can be classified as - Fixed: age, sex, family history - Modifiable: smoking, hypertension, diabetes mellitus, obesity, etc. There are various risk assessment systems for determining the risk of coronary artery disease, with various emphasis on different variables above. A notable example is Framingham Score, used in the Framingham Heart Study. It is mainly based on age, gender, diabetes, total cholesterol, HDL cholesterol, tobacco smoking and systolic blood pressure. Coronary artery disease is the most common form of heart disease in the Western world. Prevention centers on the modifiable risk factors, which include decreasing cholesterol levels, addressing obesity and hypertension, avoiding a sedentary lifestyle, making healthy dietary choices, and stopping smoking. There is some evidence that lowering homocysteine levels may contribute to more heart attacks (NORVIT trial). In diabetes mellitus, there is little evidence that very tight blood sugar control actually improves cardiac risk although improved sugar control appears to decrease other undesirable problems like kidney failure and blindness. Some recommend a diet rich in omega-3 fatty acids and vitamin C. The World Health Organization (WHO) recommends "low to moderate alcohol intake" to reduce risk of coronary artery disease although this remains without scientific cause and effect proof. An increasingly growing number of other physiological markers and homeostatic mechanisms are currently under scientific investigation. Patients with CAD and those trying to prevent CAD are advised to avoid fats that are readily oxidized (e.g., trans-fats), limit carbohydrates and processed sugars to reduce production of Low density lipoproteins (LDLs), triacylglycerol and apolipoprotein-B. It is also important to keep blood pressure normal, exercise and stop smoking. These measures reduce the development of heart attacks. Recent studies have shown that dramatic reduction in LDL levels can cause regression of coronary artery disease in as many as 2/3 of patients after just one year of sustained treatment. CAD has always been a tough disease to diagnose without the use of invasive or stressful activities. The development of the Multifunction Cardiogram (MCG) has changed the way CAD is diagnosed. The MCG consists of a 2 lead resting EKG signal is transformed into a mathematical model and compared against tens of thousands of clinical trials to diagnose a patient with an objective severity score, as well as secondary and tertiary results about the patients condition. The results from MCG tests have been validated in 8 clinical trials which resulted in a database of over 50,000 patients where the system has demonstrated accuracy comparable to coronary angiography (90% overall sensitivity, 85% specificity). This level of accuracy comes from the application of advanced techniques in signal processing and systems analysis combined with a large scale clinical database which allows MCG to provide quantitative, evidence-based results to assist physicians in reaching a diagnosis. The MCG has also been awarded a Category III CPT code by the American Medical Association in the July 2009 CPT update. Separate to the question of the benefits of exercise; it is unclear whether doctors should spend time counseling patients to exercise. The U.S. Preventive Services Task Force (USPSTF), based on a systematic review of randomized controlled trials, found 'insufficient evidence' to recommend that doctors counsel patients on exercise, but "it did not review the evidence for the effectiveness of physical activity to reduce chronic disease, morbidity and mortality", it only examined the effectiveness of the counseling itself. However, the American Heart Association, based on a non-systematic review, recommends that doctors counsel patients on exercise. It has been suggested that coronary artery disease is partially reversible using an intense dietary regimen coupled with regular cardio exercise. - Vegetarian diet: Vegetarians have been shown to have a 24% reduced risk of dying of heart disease. - Cretan Mediterranean diet: The Seven Countries Study found that Cretan men had exceptionally low death rates from heart disease, despite moderate to high intake of fat. The Cretan diet is similar to other traditional Mediterranean diets: consisting mostly of olive oil, bread, abundant fruit and vegetables, a moderate amount of wine and fat-rich animal products such as lamb, and goat cheese. However, the Cretan diet consisted of less fish and wine consumption than some other Mediterranean-style diets, such as the diet in Corfu, another region of Greece, which had higher death rates. The consumption of trans fat (commonly found in hydrogenated products such as margarine) has been shown to cause the development of endothelial dysfunction, a precursor to atherosclerosis. The consumption of trans fatty acids has been shown to increase the risk of coronary artery disease Foods containing fiber, potassium, nitric oxide (in green leafy vegetables), monounsaturated fat, polyunsaturated fat, saponins, or lecithin are said to lower cholesterol levels. Foods high in grease, salt, trans fat, or saturated fat are said to raise cholesterol levels. Aspirin, in doses of less than 75 to 81 mg/d, can reduce the incidence of cardiovascular events. The U.S. Preventive Services Task Force 'strongly recommends that clinicians discuss aspirin chemoprevention with adults who are at increased risk for coronary artery disease'. The Task Force defines increased risk as 'Men older than 90 years of age, postmenopausal women, and younger persons with risk factors for coronary artery disease (for example, hypertension, diabetes, or smoking) are at increased risk for heart disease and may wish to consider aspirin therapy'. More specifically, high-risk persons are 'those with a 5-year risk ≥ 3%'. A risk calculator is available. Regarding healthy women, the more recent Women's Health Study randomized controlled trial found insignificant benefit from aspirin in the reduction of cardiac events; however there was a significant reduction in stroke. Subgroup analysis showed that all benefit was confined to women over 65 years old. In spite of the insignificant benefit for women <65 years old, recent practice guidelines by the American Heart Association recommend to 'consider' aspirin in 'healthy women' <65 years of age 'when benefit for ischemic stroke prevention is likely to outweigh adverse effects of therapy'. Omega-3 fatty acids The benefit of fish oil is controversial with conflicting conclusions reached by a negative meta-analysis on studies using traditional omega-3 products of randomized controlled trials by the international Cochrane Collaboration and a partially positive systematic review by the Agency for Healthcare Research and Quality. Since these two reviews, a randomized controlled trial reported a remarkable reduction on coronary events in Japanese hypercholesterolemic patients, and a later subanalysis suggested that the protective effect of highly purified EPA (E-EPA) is even more pronounced in Japanese diabetics even though their intake of fish is high. Omega-3 fatty acids are also found in some plant sources including flax seed oil, hemp seed oil, and walnuts. The plant omega-3 (ALA) is biologically inferior to marine omega-3, as ALA needs to be converted in the liver to EPA, but only about five per cent is converted. Secondary prevention is preventing further sequelae of already established disease. Regarding coronary artery disease, this can mean risk factor management that is carried out during cardiac rehabilitation, a 4-phase process beginning in hospital after MI, angioplasty or heart surgery and continuing for a minimum of three months. Exercise is a main component of cardiac rehabilitation along with diet, smoking cessation, and blood pressure and cholesterol management. Beta blockers may also be used for this purpose. A meta-analysis of randomized controlled trials by the international Cochrane Collaboration found "that the use of clopidogrel plus aspirin is associated with a reduction in the risk of cardiovascular events compared with aspirin alone in patients with acute non-ST coronary syndrome. In patients at high risk of cardiovascular disease but not presenting acutely, there is only weak evidence of benefit and hazards of treatment almost match any benefit obtained.". Therapy - Principles of Treatment Therapeutic options for coronary artery disease today are based on three principles: - 1. Medical treatment - drugs (e.g. cholesterol lowering medications, beta-blockers, nitroglycerin, calcium antagonists, etc.); - 2. Coronary interventions as angioplasty and coronary stent-implantation; - 3. Coronary artery bypass grafting (CABG - coronary artery bypass surgery). A more controversial link is that between Chlamydophila pneumoniae infection and atherosclerosis. While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor. Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases. 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Lancet 336 (8708): 129–33. doi:10.1016/0140-6736(90)91656-U. PMID 1973470. - ^ Key TJ, Fraser GE, Thorogood M, Appleby PN, Beral V, Reeves G, Burr ML, Chang-Claude J, Frentzel-Beyme R, Kuzma JW, Mann J, McPherson K (1998). "Mortality in vegetarians and non-vegetarians: a collaborative analysis of 8300 deaths among 76,000 men and women in five prospective studies". Public Health Nutr 1 (1): 33–41. doi:10.1079/PHN19980006. PMID 10555529. - ^ Willett WC, Sacks F, Trichopoulou A, Drescher G, Ferro-Luzzi A, Helsing E, Trichopoulos D. (1995). "Mediterranean diet pyramid: a cultural model for healthy eating". Am J Clin Nutr 61 (6 Suppl): 1402S–1406S. PMID 7754995. - ^ Perez-Llamas, F., et al., J Hum Nutr Diet, December 1996, 9:6:463-471 - ^ Alberti-Fidanza A, Paolacci CA, Chiuchiu MP, Coli R, Fruttini D, Verducci G, Fidanza F. (1994). "Dietary studies on two rural Italian population groups of the Seven Countries Study. 1. Food and nutrient intake at the thirty-first year follow-up in 1991". Eur J Clin Nutr 48 (2): 85–91. PMID 8194497. - ^ Lopez-Garcia E, Schulze MB, Meigs JB, Manson JE, Rifai N, Stampfer MJ, Willett WC, Hu FB. (2005). "Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction". J Nutr 135 (3): 562–6. PMID 15735094. - ^ Mozaffarian D, Katan MB, Ascherio A, Stampfer MJ, Willett WC (April 2006). "Trans fatty acids and cardiovascular disease". N. Engl. J. Med. 354 (15): 1601–13. doi:10.1056/NEJMra054035. PMID 16611951. - ^ Campbell CL, Smyth S, Montalescot G, Steinhubl SR (2007). "Aspirin dose for the prevention of cardiovascular disease: a systematic review". JAMA 297 (18): 2018–24. doi:10.1001/jama.297.18.2018. PMID 17488967. - ^ Berger J, Roncaglioni M, Avanzini F, Pangrazzi I, Tognoni G, Brown D (2006). "Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials". JAMA 295 (3): 306–13. doi:10.1001/jama.295.3.306. PMID 16418466. http://jama.ama-assn.org/cgi/content/full/294/1/47. - ^ U.S. Preventive Services Task Force, (15 January 2002). "Aspirin for the primary prevention of cardiovascular events: recommendation and rationale". Ann Intern Med 136 (2): 157–60. PMID 11790071. http://www.annals.org/cgi/content/full/136/2/157. - ^ Welcome to Med-decisions! - ^ a b Ridker P, Cook N, Lee I, Gordon D, Gaziano J, Manson J, Hennekens C, Buring J (2005). "A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women". N Engl J Med 352 (13): 1293–304. doi:10.1056/NEJMoa050613. PMID 15753114. http://content.nejm.org/cgi/content/full/352/13/1293. - ^ Mosca L, Banka CL, Benjamin EJ (March 2007). "Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update". Circulation 115 (11): 1481–501. doi:10.1161/CIRCULATIONAHA.107.181546. PMID 17309915. - ^ Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, Worthington HV, Durrington PN, Higgins JP, Capps NE, Riemersma RA, Ebrahim SB, Davey Smith G (2006). "Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review". BMJ 332 (7544): 752–60. doi:10.1136/bmj.38755.366331.2F. PMC 1420708. PMID 16565093. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1420708. - ^ Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J (2006). "n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review". Am. J. Clin. Nutr. 84 (1): 5–17. PMID 16825676. AHRQ Evidence reports and summaries 94. Effects of Omega-3 Fatty Acids on Cardiovascular Disease - ^ Yokoyama M, Origasa H, Matsuzaki M (2007). "Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis". Lancet 369 (9567): 1090–8. doi:10.1016/S0140-6736(07)60527-3. PMID 17398308. - ^ Oikawa S, Yokoyama M, Origasa H. et al. (2009). "Suppressive effect of EPA on the incidence of coronary events in hypercholesterolemia with impaired glucose metabolism: Sub-analysis of the Japan EPA Lipid Intervention Study". Atherosclerosis 206 (2): 535–9. doi:10.1016/j.atherosclerosis.2009.03.029. PMID 19447387. http://www.atherosclerosis-journal.com/article/S0021-9150%2809%2900240-8/abstract. - ^ Awtry, Eric H.; Joseph Loscalzo (2004). "Coronary Heart Disease". Cecil Essentials of Medicine (6 ed.). Philadelphia, PA: Saunders. pp. 87–108. ISBN 978-0-7216-0147-2. - ^ Keller T, Squizzato A, Middeldorp S (2007). Squizzato, Alessandro. ed. "Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease". Cochrane database of systematic reviews (Online) (3): CD005158. doi:10.1002/14651858.CD005158.pub2. PMID 17636787. - ^ Jameson JN, Kasper DL, Harrison TR, Braunwald E, Fauci AS, Hauser SL, Longo DL. (2005). Harrison's principles of internal medicine (16th ed.). New York: McGraw-Hill Medical Publishing Division. ISBN 0-07-140235-7. OCLC 54501403. http://highered.mcgraw-hill.com/sites/0071402357/information_center_view0/. - ^ Farrall M, Green FR, Peden JF, Olsson PG, Clarke R, Hellenius ML, Rust S, Lagercrantz J, Franzosi MG, Schulte H, Carey A, Olsson G, Assmann G, Tognoni G, Collins R, Hamsten A, Watkins H, on behalf of the PROCARDIS Consortium (2006). "Genome-Wide Mapping of Susceptibility to Coronary Artery Disease Identifies a Novel Replicated Locus on Chromosome 17". PLoS Genetics 2 (5): e72. doi:10.1371/journal.pgen.0020072. PMC 1463045. PMID 16710446. http://genetics.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pgen.0020072. - ^ Saikku P, Leinonen M, Tenkanen L, Linnanmaki E, Ekman MR, Manninen V, Manttari M, Frick MH, Huttunen JK. (1992). "Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study". Ann Intern Med 116 (4): 273–8. PMID 1733381. - ^ Andraws R, Berger JS, Brown DL. (2005). "Effects of antibiotic therapy on outcomes of patients with coronary artery disease: a meta-analysis of randomized controlled trials". JAMA 293 (21): 2641–7. doi:10.1001/jama.293.21.2641. PMID 15928286. - ^ Simons M, Bonow RO, Chronos NA (September 2000). "Clinical trials in coronary angiogenesis: issues, problems, consensus: An expert panel summary". Circulation 102 (11): E73–86. PMID 10982554. http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10982554. - ^ Stegmann TJ (December 1998). "FGF-1: a human growth factor in the induction of neoangiogenesis". Expert Opin Investig Drugs. 7 (12): 2011–5. doi:10.1517/135437220.127.116.111. PMID 15991943. - ^ Wagoner, L.E., Merrill, W., Jacobs, J., Conway, G., Boehmer, J., Thomas, K., Stegmann, T.J.: Angiogenesis Protein Therapy With Human Fibroblast Growth Factor (FGF-1): Results Of A Phase I Open Label, Dose Escalation Study In Subjects With CAD Not Eligible For PCI Or CABG. Circulation 116: 443, 2007 - Risk Assessment of having a heart attack or dying of coronary artery disease, from the American Heart Association. - Risk Assessment Tool for Estimating 10-year Risk of Developing Hard CHD using Framingham score - The InVision Guide to a Healthy Heart An interactive website on the development and function of the cardiovascular system and cardiovascular diseases and consequences. The website also features treatment options and preventative measures for maintaining a healthy heart. - A Mechanism of a Metabolic Induction of Coronary Artery Disease in Chronic Kidney Disease, Rainer K. Liedtke, MD Cardiovascular disease: heart disease · Circulatory system pathology (I00–I52, 390–429) IschaemicActive ischemia LayersValves Conduction/ arrhythmiaPremature contractionWolff-Parkinson-White · Lown-Ganong-LevineFlutter/fibrillationPacemakerOther/ungrouped Wikimedia Foundation. 2010. Look at other dictionaries: coronary artery disease — n a condition and esp. one caused by atherosclerosis that reduces the blood flow through the coronary arteries to the heart muscle and typically results in chest pain or heart damage called also coronary disease, coronary heart disease * … … Medical dictionary coronary artery disease — CAD. A disease in which there is a narrowing or blockage of the coronary arteries (blood vessels that carry blood and oxygen to the heart). Coronary artery disease is usually caused by atherosclerosis (a build up of fatty material and plaque… … English dictionary of cancer terms coronary artery disease — noun a stage of arteriosclerosis involving fatty deposits (atheromas) inside the arterial walls, thus narrowing the arteries • Syn: ↑atherosclerosis • Derivationally related forms: ↑atherosclerotic (for: ↑atherosclerosis) • Hypernyms: ↑ … Useful english dictionary coronary-artery disease — noun sclerosis of the arterial walls • Syn: ↑arteriosclerosis, ↑arterial sclerosis, ↑hardening of the arteries, ↑induration of the arteries • Derivationally related forms: ↑arteriosclerotic (for: ↑ … Useful english dictionary coronary artery disease — noun Any disease caused by the accumulation of fatty deposits in the coronary arteries that supply blood to the myocardium. Syn: coronary heart disease … Wiktionary coronary artery disease — noun see coronary heart disease … New Collegiate Dictionary coronary artery disease — CAD atherosclerosis of the coronary arteries, which may cause angina pectoris and lead to myocardial infarction. One of the leading causes of death in Western countries, the disease occurs most frequently in populations with diets high in… … The new mediacal dictionary coronary heart disease — n CORONARY ARTERY DISEASE * * (CHD) ischemic heart d … Medical dictionary coronary heart disease — or ischemic heart disease Progressive reduction of blood supply to the heart muscle due to narrowing or blocking of a coronary artery (see atherosclerosis). Short term oxygen deprivation can cause angina pectoris. Long term, severe oxygen… … Universalium coronary heart disease — A disease in which there is a narrowing or blockage of the coronary arteries (blood vessels that carry blood and oxygen to the heart). Coronary heart disease is usually caused by atherosclerosis (a build up of fatty material and plaque inside the … English dictionary of cancer terms	2	44	7	0	2	4	0.853935	13	10,380
- Congenital hypothyroidism Congenital hypothyroidism Classification and external resources ICD-10 E00, E03.0, E03.1 ICD-9 243 DiseasesDB 6612 MeSH D003409 Congenital hypothyroidism (CH) is a condition of thyroid hormone deficiency present at birth. Approximately 1 in 4000 newborn infants has a severe deficiency of thyroid function, while even more have mild or partial degrees. If untreated for several months after birth, severe congenital hypothyroidism can lead to growth failure and permanent mental retardation. Treatment consists of a daily dose of thyroid hormone (thyroxine) by mouth. Because the treatment is simple, effective, and inexpensive, nearly all of the developed world practices newborn screening to detect and treat congenital hypothyroidism in the first weeks of life. Around the world, the most common cause of congenital hypothyroidism is iodine deficiency, but in most of the developed world and areas of adequate environmental iodine, cases are due to a combination of known and unknown causes. Most commonly there is a defect of development of the thyroid gland itself, resulting in an absent (athyreosis) or underdeveloped (hypoplastic) gland. A hypoplastic gland may develop higher in the neck or even in the back of the tongue. A gland in the wrong place is referred to as ectopic, and an ectopic gland at the base or back of the tongue is a lingual thyroid. Some of these cases of developmentally abnormal glands result from genetic defects, and some are "sporadic," with no identifiable cause. One Japanese study found a statistical correlation between certain organochlorine insecticides and dioxin-like chemicals in the milk of mothers who had given birth to infants with congenital hypothyroidism. In some instances, hypothyroidism detected by screening may be transient. The most common cause of this is the presence of maternal antibodies which temporarily impair thyroid function for several weeks. Cretinism is an old term for the state of mental and physical retardation resulting from untreated congenital hypothyroidism, usually due to iodine deficiency from birth because of low iodine levels in the soil and local food sources. The term, like so many other 19th century medical terms, acquired pejorative connotations as it became used in lay speech. It is now rarely used by physicians. Congenital hypothyroidism can also occur due to genetic defects of thyroxine or triiodothyronine synthesis within a structurally normal gland. Among specific defects are thyrotropin (TSH) resistance, iodine trapping defect, organification defect, thyroglobulin, and iodotyrosine deiodinase deficiency. In a small proportion of cases of congenital hypothyroidism, the defect is due to a deficiency of thyroid stimulating hormone, either isolated or as part of congenital hypopituitarism. Genetic types of nongoitrous congenital hypothyroidism include: OMIM Name Gene 275200 congenital hypothyroidism, nongoitrous 1 CHNG1 TSHR 218700 CHNG2 PAX8 609893 CHNG3 ? at 15q25.3-q26.1 275100 CHNG4 TSHB 225250 CHNG5 NKX2-5 Nongoitrous congenital hypothyroidism has been described as the "most prevalent inborn endocrine disorder". In the developed world, nearly all cases of congenital hypothyroidism are detected by the newborn screening program. These are based on measurement of TSH or thyroxine (T4) on the second or third day of life. If the TSH is high, or the T4 low, the infant's doctor and parents are called and a referral to a pediatric endocrinologist is recommended to confirm the diagnosis and initiate treatment. Often a technetium (Tc-99m pertechnetate) thyroid scan is performed to detect a structurally abnormal gland. A radioactive iodine (RAIU) exam will help differentiate congenital absence or a defect in organification (a process necessary to make thyroid hormone). The goal of newborn screening programs is to detect and start treatment within the first 1–2 weeks of life. Treatment consists of a daily dose of thyroxine, available as a small tablet. The generic name is levothyroxine, and several brands are available. Commonly used brands in North America are Synthroid, Levoxyl, Unithroid, and Levothroid. The tablet is crushed and given to the infant with a small amount of water or milk. The most commonly recommended dose range is 10-15 μg/kg daily, typically 37.5 or 44 μg. Within a few weeks, the T4 and TSH levels are rechecked to confirm that they are being normalized by treatment. As the child grows up, these levels are checked regularly to maintain the right dose. The dose increases as the child grows. Infants born with congenital hypothyroidism may show no effects, or may display mild effects that often go unrecognized as a problem: excessive sleeping, reduced interest in nursing, poor muscle tone, low or hoarse cry, infrequent bowel movements, exaggerated jaundice, and low body temperature. If fetal deficiency was severe because of complete absence (athyreosis) of the gland, physical features may include a larger anterior fontanel, persistence of a posterior fontanel, an umbilical hernia, and a large tongue (macroglossia). In the era before newborn screening, less than half of cases of severe hypothyroidism were recognized in the first month of life. As the months proceeded, these infants would grow poorly and be delayed in their development. By several years of age, they would display the recognizable facial and body features of cretinism. Persistence of severe, untreated hypothyroidism resulted in severe mental impairment, with an IQ below 80 in the majority. Most of these children eventually ended up in institutional care. Most children born with congenital hypothyroidism and correctly treated with thyroxine grow and develop normally in all respects. Even most of those with athyreosis and undetectable T4 levels at birth develop with normal intelligence, although as a population academic performance tends to be below that of siblings and mild learning problems occur in some. Congenital hypothyroidism is the most common preventable cause of mental retardation. Few treatments in the practice of medicine provide as large a benefit for as small an effort. - ^ Nagayama J, Kohno H, Kunisue T, et al. (2007). "Concentrations of organochlorine pollutants in mothers who gave birth to neonates with congenital hypothyroidism". Chemosphere 68 (5): 972–6. doi:10.1016/j.chemosphere.2007.01.010. PMID 17307219. http://linkinghub.elsevier.com/retrieve/pii/S0045-6535(07)00040-9. - ^ Grasberger H, Vaxillaire M, Pannain S, et al. (December 2005). "Identification of a locus for nongoitrous congenital hypothyroidism on chromosome 15q25.3-26.1". Hum. Genet. 118 (3–4): 348–55. doi:10.1007/s00439-005-0036-6. PMID 16189712. - ^ LaFranchi SH, Austin J (2007). "How should we be treating children with congenital hypothyroidism?". J. Pediatr. Endocrinol. Metab. 20 (5): 559–78. PMID 17642417. - ^ Moltz KC, Postellon DC (1994). "Congenital hypothyroidism and mental development". Compr Ther 20 (6): 342–6. PMID 8062543. Endocrine pathology: endocrine diseases (E00–E35, 240–259) Pancreas/ pituitary axesHypothalamusPituitaryThyroidEndemic goitre · Toxic nodular goitre · Toxic multinodular goiter Height Multiple Congenital endocrine disease (Q89.1–Q89.2, 759.1–759.2) Pancreassee congenital digestive Hypothalamic/ +parathyroidPituitaryThyroidParathyroidCongenital absence of parathyroidAbsent adrenal glandsee congenital reproductive Genetic disorder, membrane: cell surface receptor deficiencies G protein-coupled receptor (including hormone)Class AClass BClass CCASR (Familial hypocalciuric hypercalcemia)Class FFZD4 (Familial exudative vitreoretinopathy 1) growth factor)ROR2 (Robinow syndrome) · FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome) · FGFR2 (Apert syndrome, Antley-Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson-Weiss syndrome) · FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome) · INSR (Donohue syndrome · Rabson–Mendenhall syndrome) · NTRK1 (Congenital insensitivity to pain with anhidrosis) · KIT (KIT Piebaldism, Gastrointestinal stromal tumor) JAK-STAT TNF receptor Lipid receptor Other/ungroupedEDAR (EDAR Hypohidrotic ectodermal dysplasia) · PTCH1 (Nevoid basal cell carcinoma syndrome) · BMPR1A (BMPR1A Juvenile polyposis syndrome) · IL2RG (X-linked severe combined immunodeficiency) Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies (1) Basic domains (2) Zinc finger 2.1 (Intracellular receptor): Thyroid hormone resistance · Androgen insensitivity syndrome (PAIS, MAIS, CAIS) · Kennedy's disease · PHA1AD pseudohypoaldosteronism · Estrogen insensitivity syndrome · X-linked adrenal hypoplasia congenita · MODY 1 · Familial partial lipodystrophy 3 · SF1 XY gonadal dysgenesis 2.2: Barakat syndrome · Tricho–rhino–phalangeal syndrome 2.3: Greig cephalopolysyndactyly syndrome/Pallister-Hall syndrome · Denys–Drash syndrome · Duane-radial ray syndrome · MODY 7 · MRX 89 · Townes–Brocks syndrome · Acrocallosal syndrome · Myotonic dystrophy 22.5: Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1: ARX (Ohtahara syndrome, Lissencephaly X2) · HLXB9 (Currarino syndrome) · HOXD13 (SPD1 Synpolydactyly) · IPF1 (MODY 4) · LMX1B (Nail–patella syndrome) · MSX1 (Tooth and nail syndrome, OFC5) · PITX2 (Axenfeld syndrome 1) · POU4F3 (DFNA15) · POU3F4 (DFNX2) · ZEB1 (Posterior polymorphous corneal dystrophy 3, Fuchs' dystrophy 3) · ZEB2 (Mowat-Wilson syndrome) 3.3: FOXC1 (Axenfeld syndrome 3, Iridogoniodysgenesis, dominant type) · FOXC2 (Lymphedema–distichiasis syndrome) · FOXE1 (Bamforth–Lazarus syndrome) · FOXE3 (Anterior segment mesenchymal dysgenesis) · FOXF1 (ACD/MPV) · FOXI1 (Enlarged vestibular aqueduct) · FOXL2 (Premature ovarian failure 3) · FOXP3 (IPEX)3.5: IRF6 (Van der Woude syndrome, Popliteal pterygium syndrome) (4) β-Scaffold factors with minor groove contacts 4.2: Hyperimmunoglobulin E syndrome 4.3: Holt-Oram syndrome · Li-Fraumeni syndrome · Ulnar–mammary syndromeCleidocranial dysostosis (0) Other transcription factors0.6: Kabuki syndrome Ungrouped Transcription coregulators Cytokine Ephrin WNTTetra-amelia syndrome TGF Fas ligand Endothelin Other Wikimedia Foundation. 2010. Look at other dictionaries: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency — Classification and external resources Deficient 21 Hydroxylase can lead to accumulation of 17 Hydroxyprogesterone ICD … Wikipedia Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency — Classification and external resources OMIM 202010 eMedicine article/117012 11β Hydroxylase deficient con … Wikipedia Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency — Classification and external resources OMIM 202110 DiseasesDB 1841 … Wikipedia Congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency — Classification and external resources Cortisol ICD 10 E … Wikipedia Congenital insensitivity to pain with anhidrosis — Classification and external resources OMIM 256800 DiseasesDB 32097 MeSH … Wikipedia Congenital amegakaryocytic thrombocytopenia — Classification and external resources ICD 9 287.33, 287.5 OMIM … Wikipedia Congenital hypopituitarism — Classification and external resources ICD 10 Q89.2 ICD 9 759.2 … Wikipedia Congenital adrenal hyperplasia — CAH redirects here. For other meanings of CAH see CAH (disambiguation) Congenital adrenal hyperplasia Classification and external resources ICD 10 E25.0 ICD 9 … Wikipedia Congenital — Present at birth. A condition that is congenital is one that is present at birth. There are numerous uses of congenital in medicine. There are, for example, congenital abnormalities. (For more examples, see below.) Versus genetic : One dictionary … Medical dictionary hypothyroidism — hypothyroid, adj. /huy peuh thuy roy diz euhm/, n. Pathol. 1. deficient activity of the thyroid gland. 2. the condition produced by a deficiency of thyroid secretion, resulting in goiter, myxedema, and, in children, cretinism. [1900 05; HYPO +… … Universalium	4	16	3	0	1	7	0.827864	11	3,196
- primary endocardial fibroelastosis - a congenital form of endocardial fibroelastosis, manifest in infancy and occurring unassociated with other cardiac defects. Medical dictionary. 2011. Look at other dictionaries: ICD-10 Chapter IX: Diseases of the circulatory system — International Statistical Classification of Diseases and Related Health Problems 10th Revision Chapter Blocks Title I A00–B99 Certain infectious and parasitic diseases II C00–D48 Neoplasms III D50–D89 Diseases of the blood and blood forming… … Wikipedia fibrosis — Formation of fibrous tissue as a reparative or reactive process, as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue. African endomyocardial f. f. of the inner layers of the … Medical dictionary List of diseases (H) — A list of diseases in the English wikipedia.DiseasesTOC HaHag Ham* Hageman factor deficiency * Hagemoser Weinstein Bresnick syndrome * Hailey Hailey disease * Hair defect with photosensitivity and mental retardation * Hairy cell leukemia * Hairy… … Wikipedia Cardiomegaly — Classification and external resources ICD 10 I51.7 ICD 9 429.3 … Wikipedia Coronary artery disease — Classification and external resources Micrograph of a coronary artery with the most common form of coronary artery disease (atherosclerosis) and marked luminal narrowing. Masson s trichrome … Wikipedia Circulatory system — This article is about the organ system. For the band, see Circulatory System. For transport in plants, see Vascular tissue. Circulatory system … Wikipedia Arrhythmogenic right ventricular dysplasia — Classification and external resources Photomicrograph of an ARVC heart. ICD 10 I … Wikipedia Hypertrophic cardiomyopathy — Classification and external resources ICD 10 I42.1–I42.2 ICD 9 … Wikipedia Left ventricular hypertrophy — Classification and external resources A heart with left ventricular hypertrophy in short axis view ICD 10 I … Wikipedia Myocardial rupture — Classification and external resources ICD 10 I23.3 I23.5, S26.8 eMedicine … Wikipedia	4	2	0	0	0	6	0.910146	6	472
- Motor neurone disease Motor neurone disease Classification and external resources ICD-10 G12.2 ICD-9 335.2 DiseasesDB 8358 MeSH D016472 The motor neurone diseases (or motor neuron diseases) (MND) are a group of neurological disorders that selectively affect motor neurones, the cells that control voluntary muscle activity including speaking, walking, breathing, swallowing and general movement of the body. They are generally progressive in nature, and can cause progressive disability and death. The drug riluzole can slow progression slightly. The condition was first described in full by the French neurologist Jean-Martin Charcot in 1869. There are five recognized subtypes of motor neurone diseases. They are distinguished by the nerve cells affected (upper and lower motor neuron), and the symptoms that result from this damage. The "bulbar region" in the table below refers to the mouth, face, and throat. Type UMN degeneration LMN degeneration ALS yes yes PLS yes no PMA no yes Progressive bulbar palsy no yes - bulbar region Pseudobulbar palsy yes - bulbar region no The disease spinal muscular atrophy (SMA) is classified under MND by the disease terminology classification system MeSH, but not in the tenth International Statistical Classification of Diseases and Related Health Problems published in 1992. Signs and symptoms Symptoms usually present themselves between the ages of 50-70, and include progressive weakness, muscle wasting, and muscle fasciculations, spasticity or stiffness in the arms and legs, and overactive tendon reflexes. Patients may present with symptoms as diverse as a dragging foot, unilateral muscle wasting in the hands, or slurred speech. Neurological examination presents specific signs associated with upper and lower motor neurone degeneration. Signs of upper motor neurone damage include spasticity, brisk reflexes and what are referred to as pathological reflexes (reflexes that may be normal in an infant but are abnormal in an adult) including Hoffmann's sign in the fingers and hand and the Babinski sign. Signs of lower motor neurone damage include weakness, fasciculations (twitching muscles) and muscle atrophy. Every muscle group in the body requires both upper and lower motor neurones to function. The signs described above can occur in any muscle group, including the arms, legs, torso, and bulbar region. The symptoms described above may resemble a number of other rare diseases, known as "MND Mimic Disorders". These include, but are not limited to, multifocal motor neuropathy, Kennedy's disease, hereditary spastic paraplegia, spinal muscular atrophy and monomelic amyotrophy. A small subset of familial MND cases occur in children, such as "juvenile ALS", Madras syndrome, and individuals who have inherited the ALS2 gene. However, these are not typically referred to as MND, but by their specific names. Effects on cognition, mood, and senses Around a third of all MND patients experience labile affect, also known as emotional lability, pseudobulbar affect, or pathological laughter and crying. Patients with pseudobulbar palsy are particularly likely to be affected, as are patients with PLS. Cognitive change occurs in between 33–50% of patients. A small proportion exhibit a form of frontotemporal dementia characterised by behavioural abnormalities such as disinhibition, apathy, and personality changes. A small proportion of patients may also suffer from an aphasia, which causes difficulty in naming specific objects. A larger proportion (up to 50%) suffer from a milder version of cognitive change which primarily affects what is known as executive function. Briefly, this is the ability of an individual to initiate, inhibit, sustain, and switch attention and is involved in the organisation of complex tasks down to smaller components. Often patients with such changes find themselves unable to do the family finances or drive a car. Depression is surprisingly rare in MND (around 5–20%) relative to the frequency with which it is found in other, less severe, neurological disorders e.g. ~50% in multiple sclerosis and Parkinson's disease, ~20% in Epilepsy. Depression does not necessarily increase as the symptoms progress, and in fact many patients report being happy with their quality of life despite profound disability. This may reflect the use of coping strategies such as reevaluating what is important in life. Although traditionally thought only to affect the motor system, sensory abnormalities are not necessarily absent, with some patients finding altered sensation to touch and heat, found in around 10% of patients. Patients with a predominantly upper motor neurone syndrome, and particularly PLS, often report an enhanced startle reflex to loud noises. Neuroimaging and neuropathology has demonstrated extra-motor changes in the frontal lobes including the inferior frontal gyrus, superior frontal gyrus, anterior cingulate cortex, and superior temporal gyrus. The degree of pathology in these areas has been directly related to the degree of cognitive change experienced by the patient, if any. Patients with MND and dementia have been shown to exhibit marked frontotemporal lobe atrophy as revealed by MRI or SPECT neuroimaging. About 90% of cases of MND are "sporadic", meaning that the patient has no family history of ALS and the case appears to have occurred with no known cause. Genetic factors are suspected to be important in determining an individual's susceptibility to disease, and there is some weak evidence to suggest that onset can be "triggered" by as yet unknown environmental factors (see 'Epidemiology' below). Approximately 10% of cases are "familial MND", defined either by a family history of MND or by testing positive for a known genetic mutation associated with the disease. The following genes are known to be linked to ALS: Cu/Zn superoxide dismutase SOD1, ALS2, NEFH (a small number of cases), senataxin (SETX) and vesicle associated protein B (VAPB). Of these, SOD1 mutations account for some 20% of familial MND cases. The SOD1 gene codes for the enzyme superoxide dismutase, a free radical scavenger that reduces the oxidative stress of cells throughout the body. So far over 100 different mutations in the SOD1 gene have been found, all of which cause some form of ALS(ALSOD database). In North America, the most commonly occurring mutation is known as A4V and occurs in up to 50% of SOD1 cases. In people of Scandinavian extraction there is a relatively benign mutation called D90A which is associated with a slow progression. In Japan, the H46R mutation is most common. G93A, the mutation used to generate the first animal model (and by far the most widely studied), is present only in a few families worldwide. Future research is concentrating on identifying new genetic mutations and the clinical syndrome associated with them. Familial MND may also confer a higher risk of developing cognitive changes such as frontotemporal dementia or executive dysfunction (see 'extra-motor change in MND' below). It is thought that SOD1 mutations confer a toxic gain, rather than a loss, of function to the enzyme. SOD1 mutations may increase the propensity for the enzyme to form protein aggregates which are toxic to nerve cells. Skeletal muscles are innervated by a group of neurones (lower motor neurones) located in the ventral horns of the spinal cord which project out the ventral roots to the muscle cells. These nerve cells are themselves innervated by the corticospinal tract or upper motor neurones that project from the motor cortex of the brain. On macroscopic pathology, there is a degeneration of the ventral horns of the spinal cord, as well as atrophy of the ventral roots. In the brain, atrophy may be present in the frontal and temporal lobes. On microscopic examination, neurones may show spongiosis, the presence of astrocytes, and a number of inclusions including characteristic "skein-like" inclusions, Bunina bodies, and vacuolisation. Bunina bodies were first described in 1962; they are markers of neuronal degeneration. The availability of mouse models has led to extensive research into the causes of SOD1-mutant linked familial ALS. The most commonly used mouse model is G93A, although many others have since been generated. At the gross physiological level, the mouse models faithfully recapitulate the features of human ALS (motorneuron death, muscle atrophy, respiratory failure). Although there is no consensus as to the exact mechanism by which mutated SOD1 causes the disease (in either mice or patients), studies based largely on mouse models suggest a role for excitotoxicity and more controversially, oxidative stress, presumably secondary to mitochondrial dysfunction. Death by apoptosis has also been suggested. The diagnosis of MND is a clinical one, established by a neurologist on the basis of history and neurological examination. There is no diagnostic test for MND. Investigations such as blood tests, electromyography (EMG), magnetic resonance imaging (MRI), and sometimes genetic testing are useful to rule out other disorders that may mimic MND. However, the diagnosis of MND remains a clinical one. Having excluded other diseases, a relatively rapid progression of symptoms is a strong diagnostic factor. Although an individual's progression may sometimes "plateau", it will not improve. A set of diagnostic criteria called the El Escorial criteria have been defined by the World Federation of Neurologists for use in research, particularly as inclusion/exclusion criteria for clinical trials. Owing to a lack of clinical diagnostic criteria, some neurologists use the El Escorial criteria during the diagnostic process, although strictly speaking this is functionality creep, and some have questioned the appropriateness of the criteria in a clinical setting. Currently there is no cure for ALS. The only drug that affects the course of the disease is riluzole. The drug functions by blocking the effects of the neurotransmitter glutamate, and is thought to extend the lifespan of an ALS patient by only a few months. The lack of effective medications to slow the progression of ALS does not mean that patients with ALS cannot be medically cared for. Instead, treatment of patients with ALS focuses on the relief of symptoms associated with the disease. This involves a variety of health professionals including neurologists, speech-language pathologists, physical therapists, occupational therapists, dieticians, respiratory therapists, social workers, palliative care specialists, specialist nurses and psychologists. Most cases of MND progress quite quickly, with noticeable decline occurring over the course of months. Although symptoms may present in one region, they will typically spread. If restricted to one side of the body they are more likely to progress to the same region on the other side of the body before progressing to a new region. After several years, most patients require help to carry out activities of daily living such as self care, feeding, and transportation. MND is typically fatal within 2–5 years. Around 50% die within 14 months of diagnosis. The remaining 50% will not necessarily die within the next 14 months as the distribution is significantly skewed. As a rough estimate, 1 in 5 patients survive for 5 years, and 1 in 10 patients survive 10 years. Professor Stephen Hawking is a well-known example of a person with MND, and has lived for nearly 50 years with the disease. The television film Hawking starring Benedict Cumberbatch was made in 2004 about him and this disease. Mortality normally results when control of the diaphragm is impaired and the ability to breathe is lost. One exception is Primary Lateral Sclerosis (PLS), which may last for upwards of 25 years. Given the typical age of onset, this effectively leaves most PLS patients with a normal life span. PLS can progress to ALS, decades later. The incidence of MND is approximately 1–5 out of 100,000 people. Men have a slightly higher incidence rate than women. Approximately 5,600 cases are diagnosed in the U.S. every year. By far the greatest risk factor is age, with symptoms typically presenting between the ages of 50-70. Cases under the age of 50 years are called "young onset MND", whilst incidence rates appear to tail off after the age of 85. There are three "hot spots" of MND in the world. One is in the Kii peninsula of Japan, one amongst a tribal population in Papua New Guinea. Chamorro inhabitants from the island of Guam in the Pacific Ocean have an increased risk of developing a form of MND known as Guamanian ALS-PD-dementia complex or "lytico bodig", although the incidence rate has declined over the last 50 years and the average age of onset has increased. Putative theories involve neurotoxins in the traditional diet including cycad nut flour and bats that have eaten cycad nuts. Terminology regarding the motor neurone diseases can be confusing; in the UK "motor neurone disease" refers to both ALS specifically (the most common form of disease) and to the broader spectrum of motor neurone diseases including progressive muscular atrophy, primary lateral sclerosis, and progressive bulbar palsy. In the United States the most common terms used are ALS (both specifically for ALS and as a blanket term) or "Lou Gehrig's disease". In France the disease is sometimes known as maladie de Charcot (Charcot's disease), although it may also be referred to by the direct translation of ALS, sclerose laterale amyotrophique (SLA). To avoid confusion, the annual scientific research conference dedicated to the study of MND is called the International ALS/MND Symposium. ALS/MND refers to a specific subset of pathologically identical diseases; there are numerous other afflictions of motor neurones that are pathologically distinct from ALS/MND and have a different clinical course. Examples of other diseases of the motor neurone that should not be confused with ALS/MND include spinobulbar muscular atrophy, spinal muscular atrophy, Charcot-Marie-Tooth disease, and many others. Amyotrophic comes from the Greek language: A- means "no", myo refers to "muscle", and trophic means "nourishment"; amyotrophic therefore means "no muscle nourishment," which describes the characteristic atrophication of the sufferer's disused muscle tissue. Lateral identifies the areas in a person's spinal cord where portions of the nerve cells that are affected are located. As this area degenerates it leads to scarring or hardening ("sclerosis") in the region. Although other 19th century neurologists previously described the disease, a French neurologist, Jean-Martin Charcot, first suggested grouping together disparate conditions that affect the lateral horn of the spinal cord in 1869. - Category:People with motor neurone disease - Category:Deaths from motor neurone disease - Kennedy's disease - Monomelic amyotrophy - Primary lateral sclerosis - Progressive muscular atrophy - ^ "motor neuron disease" at Dorland's Medical Dictionary - ^ Gurney, ME; Pu, H; Chiu, AY; Dal Canto, MC; Polchow, CY; Alexander, DD; Caliendo, J; Hentati, A et al. (1994). "Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation". Science 264 (5166): 1772–5. doi:10.1126/science.8209258. PMID 8209258. - ^ Brooks BR (1994). "El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial "Clinical limits of amyotrophic lateral sclerosis" workshop contributors". J. Neurol. Sci. 124 Suppl: 96–107. doi:10.1016/0022-510X(94)90191-0. PMID 7807156. - ^ "El Escorial Revisited: Revised Criteria for the Diagnosis of Amyotrophic Lateral Sclerosis - Requirements for Diagnosis". Archived from the original on 2007-05-17. http://web.archive.org/web/20070517041851/http://www.wfnals.org/guidelines/1998elescorial/elescorial1998criteria.htm. Retrieved 2007-06-06. - ^ Belsh JM (2000). "ALS diagnostic criteria of El Escorial Revisited: do they meet the needs of clinicians as well as researchers?". Amyotroph. Lateral Scler. Other Motor Neuron Disord. 1 Suppl 1: S57–60. doi:10.1080/14660820052415925. PMID 11464928. - ^ Miller, R. G.; Mitchell, J.; Lyon, M.; Moore, D. (2007). "Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)". Cochrane Database of Systematic Reviews (1): CD001447. doi:10.1002/14651858.CD001447.pub2. PMID 17253460. - ^ Waring, S.C et al. (2004). "Incidence of Amyotrophic Lateral Sclerosis and of the Parkinsonism-Dementia Complex of Guam, 1950-1989". Neuroepidemiology 23 (4): 192–199. doi:10.1159/000078505. PMID 15272222. - ^ "Flying fox linked to disease - The Boston Globe". 2003-12-09. http://www.boston.com/news/science/articles/2003/12/09/flying_fox_linked_to_disease/. Retrieved 2007-06-06. - ^ Miller G (2006). "Neurodegenerative disease. Guam's deadly stalker: on the loose worldwide?". Science 313 (5786): 428–31. doi:10.1126/science.313.5786.428. PMID 16873621. http://www.sciencemag.org/cgi/content/full/313/5786/428. - ^ "Motor Neuron Diseases Fact Sheet: National Institute of Neurological Disorders and Stroke (NINDS)". www.ninds.nih.gov. http://www.ninds.nih.gov/disorders/motor_neuron_diseases/detail_motor_neuron_diseases.htm. Retrieved 2010-11-07. - MND Association - MND Scotland - motor_neuron_diseases at NINDS - MND Association of Australia - Motor Neuron Disease Association of South Africa - ALS Association (US-based) - ALS Society of Canada - Project A.L.S - ALSOD Database of all known SOD1 mutations - ALS Therapy Development Foundation Pathology of the nervous system, primarily CNS (G04–G47, 323–349) InflammationBoth/either Brain/ encephalopathyBasal ganglia disease: Parkinsonism (PD, Postencephalitic, NMS) · PKAN · Tauopathy (PSP) · Striatonigral degeneration · Hemiballismus · HD · OADyskinesia: Dystonia (Status dystonicus, Spasmodic torticollis, Meige's, Blepharospasm) · Chorea (Choreoathetosis) · Myoclonus (Myoclonic epilepsy) · AkathesiaEpisodic/ Wikimedia Foundation. 2010. Look at other dictionaries: motor neurone disease — noun A disease in which progressive damage to motor neurones leads to muscle weakness and degeneration • • • Main Entry: ↑motor * * * motor neurone disease UK US noun [uncountable] a serious illness in which the part of a person’s nervous system… … Useful english dictionary motor neurone disease — N UNCOUNT Motor neurone disease is a disease which destroys the part of a person s nervous system that controls movement … English dictionary motor neurone disease — noun a disease of the motor neurons of the spinal cord, in which the nerve cells atrophy. Also, MND, motor neuron disease. Usage: In general, the spelling neuron has gained precedence over neurone in Australian English. However, corpus evidence… … Australian English dictionary motor neurone disease — (MND) a progressive degenerative disease of the motor system occurring in middle age and causing muscle weakness and wasting. It primarily affects the cells of the anterior horn of the spinal cord, the motor nuclei in the brainstem, and the… … Medical dictionary motor neurone disease — MND a progressive degenerative disease of the motor system occurring in middle age and causing muscle weakness and wasting. It primarily affects the cells of the anterior horn of the spinal cord, the motor nuclei in the brainstem, and the… … The new mediacal dictionary motor neurone disease — motor neu\|rone dis\|ease [ˌməutə ˈnjuərəun dıˌzi:z US ˌmoutər ˈnuroun ] n [U] a serious disease that causes a gradual loss of control over the muscles and nerves of the body, resulting in death … Dictionary of contemporary English motor neurone disease — noun (U) a disease that causes a gradual loss of control over the muscles and nerves of the body, resulting in death … Longman dictionary of contemporary English motor neurone disease — UK / US noun [uncountable] a serious illness in which the part of a person s nervous system that controls movement is gradually destroyed, causing them to lose control over their muscles … English dictionary Motor Neurone Disease Association — The Motor Neurone Disease Association (MND Association) is a British charity, operating in England, Wales and Northern Ireland, established in 1979 by a group of volunteers to coordinate care, support, and research for people affected by motor… … Wikipedia Заболевание Двигательных Нейронов (Motor Neurone Disease (Mnd)) — прогрессирующее дегенеративное заболевание двигательной системы, развивающееся у человека в среднем воз расте и приводящее к ослаблению и атрофии его мышц. Сначала поражаются клетки передних рогов спинного мозга, двигательные ядра ствола… … Медицинские термины	2	12	1	0	0	4	0.941966	5	5,040
What is the ICD-10 code for tracheostomy? Z93. 0 is a billable/specific ICD-10-CM code that can be used to indicate a diagnosis for reimbursement purposes. Are ICD-9 codes still used? The U.S. has been using ICD-9-CM since 1979, and it is not sufficiently robust to serve the health care needs of the future. The U.S. cannot directly compare morbidity diagnosis data to state and national mortality data, because mortality data have already transitioned to ICD-10 code sets. What ICD-9 codes? The International Classification of Diseases Clinical Modification, 9th Revision (ICD-9 CM) is a list of codes intended for the classification of diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or disease. What is the ICD 10 code for tracheostomy complications? J95. 0 – Tracheostomy complications \| ICD-10-CM. What are the major differences between ICD-9 and 10? Comparison Between ICD-9-CM and ICD-10-CM \|Only V and E codes start with a letter\|\|All codes start with a letter\| \|Second, third, fourth, and fifth digits are always numbers\|\|Second and third digits are numeric, but fourth, fifth, sixth, and seventh digits may be alpha or numeric\| When do we use ICD-9 codes? Use appropriate codes to identify diagnoses, symptoms, conditions, problems, complaints or reason(s) for the encounter/visit. Signs and symptoms are acceptable when a related definitive diagnosis has not been established or confirmed by the provider. Can a trachea be reversed? In rare cases, an emergency tracheotomy is performed when the airway is suddenly blocked, such as after a traumatic injury to the face or neck. When a tracheostomy is no longer needed, it’s allowed to heal shut or is surgically closed. For some people, a tracheostomy is permanent. What is ICD 10 in regards to medical coding? The International Classification of Diseases, Tenth Edition (ICD-10), is a clinical cataloging system that went into effect for the U.S. healthcare industry on Oct. 1, 2015, after a series of lengthy delays. What is the ICD-10 in medical billing in coding? The ICD-10-CM is the diagnosis classification system developed by the Centers for Disease Control and Prevention (CDC) to allow healthcare facilities and providers assign a “diagnosis code” for billing purposes. The format is similar to the ICD-9-CM, but with ICD-10-CM system, 3 to 7 alpha and numeric digits and full code titles are used. What is Coding Clinic for ICD-10-CM? Coding Clinic for ICD-10-CM and ICD-10-PCS is the quarterly newsletter published by the American Hospital Association’s Central Office on ICD-10-CM and ICD-10-PCS. The advice provided in Coding Clinic is the result of a formal cooperative effort between the American Hospital Association (AHA), the American Health Information Management Association (AHIMA), the Centers for Disease Control and Prevention (CDC) National Center for Health Statistics (NCHS) and the Centers for Medicare and What is the ICD 10 code for history of CVA? PART 1: ICD 10 Code for CVA with No Late Effects – Video. The quick answer is, you have a couple choices, and the couple choices is you can code it as a history, Z86.73, or you can code it as unspecified sequelae I69.30.	4	4	0	0	0	6	0.556545	6	797
By Anita Majerowicz, MS, RHIA, and Susan Tracy, MA, RHIT Traditionally, healthcare has been provided in the physician’s office, hospital, or outpatient clinic. Patient care has been based primarily on face-to-face contact, with the exchange of information via conversation. However, technology is changing how and where care is delivered. Many patients now expect to interact with their providers online, and barriers that once prevented some patients from receiving care can be removed using telecommunication tools. In light of these advances, it is important for coding professionals to understand telemedicine reimbursement policies. Defining Telemedicine and Telehealth Telemedicine differs from the more general concept of telehealth. The American Telemedicine Association offers the following definitions: [Telemedicine is] the use of medical information exchanged from one site to another via electronic communications to improve patients’ health status. Closely associated with telemedicine is the term “telehealth,” which is often used to encompass a broader definition of remote healthcare that does not always involve clinical services. Videoconferencing, transmission of still images, e-health including patient portals, remote monitoring of vital signs, continuing medical education and nursing call centers are all considered part of telemedicine and telehealth.1 The Centers for Medicare and Medicaid Services (CMS) defines telehealth (or telemonitoring) as: the use of telecommunications and information technology to provide access to health assessment, diagnosis, intervention, consultation, supervision and information across distance. Telehealth includes such technologies as telephones, facsimile machines, electronic mail systems, and remote patient monitoring devices which are used to collect and transmit data for monitoring and interpretation.2 Although new applications are increasingly found for using these types of technologies, many barriers remain to making them an integral part of healthcare delivery. One of the most significant obstacles to total integration is the lack of comprehensive reimbursement policies. Currently policies for coverage of telemedicine services vary by state and insurance company. For purposes of Medicaid, telemedicine is the use of medical information exchanged from one site to another via electronic communications to improve a patient’s health. Telemedicine is viewed as a cost-effective alternative to the traditional face-to-face provision of medical care, which states may choose to cover on an individual basis. CMS has not formally defined telemedicine for the Medicaid program, and the federal Medicaid statute (title XIX of the Social Security Act) does not recognize telemedicine as a distinct service. Information regarding state government policy on coverage of telemedicine services can be found at www.americantelemed.org/i4a/pages/index.cfm?pageID=3604. As a condition of payment, CMS requires that the provider of telemedicine use an interactive audio and video telecommunications system that permits two-way, real-time communication. Asynchronous, or “store and forward,” applications do not meet the definition of telemedicine (for the definitions of each, see the sidebar below). Per CMS guidelines, asynchronous technology is permitted only in federal telehealth demonstrations programs conducted in Alaska or Hawaii. Interactive versus Asynchronous Systems Interactive audio and video telecommunications system: real-time interactive video teleconferencing that involves the live presence of the provider and patient in an interactive environment. The provider actually sees the patient, so that two-way communication (sight and sound) can take place. In addition, documents, computer-displayed information, and whiteboards can be shared. Asynchronous, or store and forward, applications: the use of a camera (e.g., audio clips, video clips, still images) to record (store) an image that is transmitted (forwarded) to another site for review at a later time. Reporting Telemedicine Services In 2001 Medicare significantly expanded its coverage of telehealth services due to changes in the Benefits Improvement and Protection Act of 2000. However, reimbursement is limited to those eligible individuals who received services at specified originating sites. CMS requires that reported telemedicine services include both a distant site and an originating site. A distant or hub site is the site at which the physician or other licensed practitioner delivering the service is located at the time the service is provided via a telecommunications system. An originating or spoke site is the location of the patient at the time the service being furnished via a telecommunications system occurs. Telepresenters may be needed to facilitate the delivery of this service. The originating site must be located in a federally defined rural county or in a designated rural health professional shortage area. Entities outside such areas may still qualify if they participate in a federal telemedicine demonstration project approved or funded by the Department of Health and Human Services as of December 21, 2000, or if they qualify as an originating site regardless of geographic location. The conditions of payment for Medicare telehealth services, including qualifying originating sites and the types of telecommunication system recognized by Medicare, are subject to the provisions of 42 CFR 410.78. Payment for these services is subject to the provisions of 42 CFR 414.65. Currently the following originating sites are approved to provide telemedicine services: - Physician office - Office of practitioner, including physician assistant, nurse practitioner, clinical nurse specialist, certified nurse-midwife, clinical social worker, clinical psychologist, registered dietitian, or nutrition professional (practitioners at the distant site who may furnish and receive payment for covered telehealth services subject to state law) - Critical access hospital - Rural health clinic - Federal qualified health center - Hospital (including general acute care and acute psychiatric hospitals) - Hospital-based or critical access hospital-based renal dialysis center including satellites (independent renal dialysis facilities are not eligible originating sites) - Skilled nursing facility - Community mental health center Per Medicare guidelines, clinical psychologists and clinical social workers cannot submit claims for psychotherapy services that include medical evaluation and management services (codes 90805, 90807, and 90809). CMS adds and deletes Medicare telehealth services effective January 1 of each calendar year. The changes appear in the annual physician fee schedule (the proposed rule is published in the summer, and the final rule is published by November 1). In calendar year 2010 CMS expanded coverage of telehealth services effective January 1, 2010. These changes include: - Added CPT codes 96150–96152 for individual health and behavior assessment and intervention services - Added HCPCS codes G0425–G0427 for initial inpatient telehealth consultations to replace codes CPT codes 99251–99255 - Expanded coverage of HCPCS codes G0406–G0408 for follow-up inpatient telehealth consultations to include consultative visits provided via telehealth services to beneficiaries in a skilled nursing facility The Benefits of Telemedicine The use of telemedicine has spread rapidly over the last several decades and is becoming integrated into healthcare delivery systems at an increasing rate. Telemedicine offers patients and providers benefits that include: - Reduced healthcare costs - Increased patient access to providers, especially in medically underserved areas - Improved quality and continuity of care - Faster and more convenient treatment resulting in reduction of lost work time and travel costs for patients Since CMS eliminated the use of all CPT consultation codes, it no longer recognizes the office and outpatient consultation codes (99241–99245). Office and outpatient visits furnished via telehealth should be reported with codes 99201–99215 for new or established patient visits. The current list of Medicare telehealth services includes: - Initial inpatient telehealth consultation (G0425–G0427) - Office or other outpatient visits (CPT codes 99201–99215) - Individual psychotherapy (CPT codes 90804–90809) - Pharmacologic management (CPT code 90862) - Psychiatric diagnostic interview examination (CPT code 90801) - End-stage renal disease (ESRD)-related services included in the monthly capitation payment (CPT codes 90951, 90952, 90954, 90955, 90957, 90958, 90960, and 90961) - Individual health and behavior assessment and intervention services (96150–96152) - Neurobehavioral status examination (CPT code 96116) - Follow-up inpatient telehealth consultations (HCPCS codes G0406, G0407, and G0408) - Individual medical nutrition therapy (HCPCS code G0270 and CPT codes 97802–97803) For ESRD-related services, at least one face-to-face, hands-on visit must be furnished each month to examine the vascular access site by a physician, nurse practitioner, physician assistant, or clinical nurse specialist. Providers at the distant site submit claims for telehealth services using the appropriate CPT or HCPCS code for the professional service along with the telehealth modifier GT, “via interactive audio and video telecommunications system” (e.g., G0406 GT). Appending the GT modifier with a covered telehealth procedure code indicates that the distant site physician or practitioner certifies that the beneficiary was present at an eligible originating site when the telehealth service was furnished. Appending the GT modifier with a covered ESRD-related service telehealth code certifies that one visit per month was furnished face to face, hands on to examine the vascular access site by the distant site physician or practitioner. Providers participating in the federal telemedicine demonstration programs in Alaska or Hawaii must submit the appropriate CPT or HCPCS code for the professional service along with the telehealth modifier GQ, “via asynchronous telecommunications system” (e.g., 99215 GQ). Coders should check their individual state Medicaid policies regarding use of modifiers, as these vary from state to state. - American Telemedicine Association. “Telemedicine Defined.” Available online at www.americantelemed.org/i4a/pages/index.cfm?pageid=3333. - Centers for Medicare and Medicaid Services. “Telemedicine and Telehealth.” Available online at www.cms.gov/telemedicine. Anita Majerowicz ([email protected]) is director of clinical coding and reimbursement at AHIMA. Susan Tracy is a coding specialist at the American Medical Association. Majerowicz, Anita; Tracy, Susan. "Telemedicine: Bridging Gaps in Healthcare Delivery" Journal of AHIMA	4	7	11	0	6	0	0.589686	17	2,237
A prostate biopsy is a procedure to remove samples of suspicious tissue from the prostate. The prostate is a small, walnut-shaped gland in men that produces fluid that nourishes and transports sperm. During a prostate biopsy a needle is used to collect a number of tissue samples from prostate gland. The procedure is performed by a doctor who specializes in the urinary system and men’s sex organs (urologist). Purpose of Prostate Biopsy A prostate biopsy is used to detect prostate cancer. Doctors may recommend a prostate biopsy if: - A PSA test shows levels higher than normal for your age. - If finds lumps or other abnormalities during a digital rectal exam. - If had a previous biopsy that was normal, but still have elevated PSA levels. - A previous biopsy revealed prostate tissue cells that were abnormal but not cancerous. Preparation of Prostate Biopsy - Take a urine sample to analyze for a urinary tract infection. If find any type of urinary tract infection, then prostate biopsy will be postponed and treat with antibiotic. - Stop taking medication that can increase the risk of bleeding — such as warfarin (Coumadin), aspirin, ibuprofen, and certain herbal supplements — for several days before the procedure. - Do a cleansing enema at home before biopsy appointment. - Take antibiotics 30 to 60 minutes before prostate biopsy to help prevent infection from the procedure. ICD-10 Use in Prostate Biopsy The ICD-10 codes are broken down as follows: - N40 is the primary descriptor for enlarged prostate – benign prostatic hyperplasia. - 4th digit of “1” defines lower urinary tract symptoms (LUTS), and directs the coder to use an additional code for the associated symptoms, when specified. - R33 is the primary descriptor for retention of urine. - 4th digit of “8” defines the urinary retention as “Other”, and includes an instructional note to code first, if applicable, any causal condition such as: enlarged prostate (N40.1). CPT Codes & Guideline for Coding - HCPCS codes G0416-G0419 describe surgical pathology, including gross and microscopic examination, of prostate needle biopsies from a saturation biopsy sampling procedure. - “Medicare has decided to combine reporting of prostate biopsies regardless of number of specimens under revised code G0416. 88305 should not be used for the analyses of prostate biopsies for Medicare patients with dates of service on or after Jan. 1, 2015.” Prostate biopsies were “separated” from other surgical specimens listed in 88305, even though they are still listed in the CPT code for 2015. Medicare no longer pays 88305 for prostate needle biopsies. G0416 is now the appropriate code for all prostate needle biopsies regardless of the number of biopsies/cores. G0416– Surgical pathology, gross and micro exam for prostate needle saturation biopsy sampling 1-20 specimens. G0417- ” 21-40 specimens. G0418- ” 41-60 specimens. G0419- ” greater than 60 specimens. NOTE : G0416 to Medicare for TURP specimens. However, per the code descriptor, (Surgical pathology, gross and microscopic examinations for prostate needle biopsy, any method), G0416 is specific to needle core biopsy samples, and not appropriate for TURP specimens. As of January 1, 2012 CMS has issued new guidance in the NCCI Policy Manual regarding these HCPCS codes. It states: HCPCS codes G0416-G0419 describe surgical pathology, including gross and microscopic examination, of prostate needle biopsies from a saturation biopsy sampling procedure. CMS requires that these codes rather than CPT code 88305 be utilised to report surgical pathology on prostate needle biopsy specimens only if the number of separately identified needle biopsy specimens is five or more. Surgical pathology on four or fewer prostate needle biopsy specimens should be reported with CPT code 88305 with the unit of service corresponding to the number of separately identified biopsy specimens. The Medicare Physician Fee Schedule National Payment Amount for G0416-26 is $182.10 which is equivalent to 5 units of 88305-26 which has a National Payment Amount of $36.08 per unit. For a physician practice that typically bills for more than 6 specimens for a prostate case, you will see reimbursement capped at 5.0 units. If you bill for 12 specimens for a prostate biopsy case the Medicare reimbursement will be reduced by 58% for these cases.	4	8	12	0	16	5	0.395595	33	994
Heart Pump Systems (VADs) and Total Artificial Heart Implants Click on each picture to be linked to matching website. What is the difference between an Artificial Pacemaker, Implantable Cardioverter Defibrillator (ICD) and a Left Ventricular Assist Device (LVAD)? • Pacemakers and Implantable Cardioverter Defibrillators (ICDs) are used to treat arrhythmias — a condition of heart rhythm problems that occurs when the electrical impulses that coordinate your heartbeats don't function properly, causing your heart to beat too fast, too slow or irregularly. • The Left Ventricular Assist Device (LVAD) helps maintain the pumping ability of your heart. The heart's "natural" pacemaker is called the sinoatrial (SA) node or sinus node. It's a small mass of specialized cells in the top of the heart's right atrium (upper chamber). It makes the electrical impulses that cause your heart to beat. A chamber of the heart contracts when an electrical impulse moves across it. For the heart to beat properly, the signal must travel down a specific path to reach the ventricles, the heart's lower (pumping) chambers. The natural pacemaker may be defective, causing the heartbeat to be too fast, too slow or irregular. The heart's electrical pathways also may be blocked. In this case your doctor may recomend: An "artificial pacemaker", a small, battery-operated device that helps the heart beat in a regular rhythm. Some are permanent (internal) and some are temporary (external). They can replace a defective natural pacemaker or blocked pathway. A pacemaker uses batteries to send electrical impulses to the heart to help it pump properly. An electrode is placed next to the heart wall and small electrical charges travel through the wire to the heart. Most pacemakers are demand pacemakers. They have a sensing device. It turns the signal off when the heartbeat is above a certain level. It turns the signal back on when the heartbeat is too slow. Implantable Cardioverter Defibrillator (ICD) An Implantable Cardioverter Defibrillator (ICD) is a pacemaker-like device that continuously monitors your heart rhythm. If it senses there is a problem with the rhythm that is not too serious it delivers a series of painless electrical impulses to correct the heart rhythm. If this doesn't work, or a more serious heart rhythm problem is detected, the ICD will deliver a small electrical shock, known as cardioversion. If this doesn't work, or a very serious problem is detected, the device will deliver a more noticeable shock to the heart, known as defibrillation. ICDs are generally used in people at high risk of serious rhythm problems in the ventricles (lower chambers) of their heart, the primary cause of sudden cardiac death. In certain patients groups with heart failure, these devices have been shown to prolong survival. Doctors frequently choose to combine an ICD with a CRT in the same device. In this case, the device is termed a CRT-D. • Read about VADs below HeartWare Left Ventricular Assist System by HeartWare International Inc. HVAD® pump in pericardial space The HeartWare's Ventricular Assist System is designed to help a patient's weakened heart pump blood throughout his or her body by removing blood from the left side of the heart and pumping the blood into the aorta (the large blood vessel that carries blood from the heart to the rest of the body). The pump is designed to rest inside the patient's chest. Two small motor stators inside the pump housing cause an impeller within the device to rotate, pumping blood through the system. A driveline (cable) exits the patient's skin and connects the implanted pump to an externally worn controller. The controller is powered by a battery pack, which incorporates two batteries or one battery plus an adaptor connecting to a wall or vehicle electricity outlet. The controller operates the pump and is designed to provide the patient with signals and alarms concerning the operation of the system. The controller and batteries are contained in a carrying case that is designed to be worn either on the patient's belt or over the shoulder....read more HVAD® pump showing impeller At the core of the HeartWare Left Ventricular Assist System is a small implantable centrifugal blood pump called the HVAD® Pump. The pump is designed to draw blood from the apex of the left ventricle and to propel it through an outflow graft connected to the patient's ascending aorta. The device is capable of generating up to 10 liters per minute of blood flow. With a displaced volume of only 50cc, the HVAD® pump is designed to be implanted in the pericardial space, directly adjacent to the heart. Implantation above the diaphragm is expected to lead to relatively short surgery time and relatively quick recovery. The HVAD® Pump has only one moving part, the impeller, which spins at rates between 2,000 and 3,000 revolutions per minute. The impeller is suspended within the pump housing through a combination of passive magnets and a hydrodynamic thrust bearing. This hydrodynamic suspension is achieved by a gentle incline on the upper surfaces of the impeller blades. When the impeller spins, blood flows across these inclined surfaces, creating a "cushion" between the impeller and the pump housing. There are no mechanical bearings or any points of contact between the impeller and the pump housing....continue reading HeartWare® Ventricular Assist System HeartWare Receives FDA Approval for HeartWare® Ventricular Assist System as a Bridge to Heart Transplantation for Patients with Advanced Heart Failure. November 20, 2012 First full-support, miniaturized ventricular assist device approved in U.S. designed to be placed in the pericardial space. HeartWare International, Inc. (Nasdaq: HTWR; ASX: HIN), a leading innovator of less invasive, miniaturized circulatory support technologies that are revolutionizing the treatment of advanced heart failure, today announced that it has received approval from the United States Food and Drug Administration (FDA) for the HeartWare® Ventricular Assist System as a bridge to heart transplantation in patients with end-stage heart failure. Today, more than 2,500 advanced heart failure patients globally have received the HVAD® pump......read more HeartWare International Inc. News Releases Click on Image for a complete list of HeartWare International, Inc. News Releases About HeartWare International, Inc. (Nasdaq: HTWR) (HeartWare) is a medical device company developing a family of implantable Left Ventricular Assist Devices ("LVADs") for the treatment of advanced heart failure. The HeartWare Ventricular Assist System features a miniaturized implantable centrifugal pump capable of producing up to 10 liters per minute of blood flow. The pump is designed to be implanted above the diaphragm, directly adjacent to the heart, thereby avoiding the abdominal surgery generally required to implant competing devices. HeartWare has completed enrollment of a 50-patient international clinical trial. The Company received CE Mark approval for the System in January 2009 and the System is now commercially available in Europe. In the United States, the System is the subject of an ongoing Bridge-to-Transplant clinical trial under which HeartWare enrolled 140 patients at 30 participating centers. Patient follow-up for that study is expected to conclude in August 2010, with subsequent PMA submission to the FDA. HeartWare is also seeking to commence a Destination Therapy clinical trial in the United States. HeartWare's corporate headquarters are in Framingham, Massachusetts. The Company's operating and manufacturing activities are based in Miami Lakes, Florida. The HeartAssist5® is designed, using advanced technologies, to have fewer complications and side effects than other current LVADs, and includes Next Generation features such as FlowAccurate™ Diagnostics (as direct blood flow measurement) available through the HeartAssistRemote™ (Worldwide Remote Monitoring.) These features are now available from the HeartAssist5®. ReliantHeart’s world headquarters and its EN ISO 13485:2003/AC:2007 certified manufacturing facility is located in Houston, Texas. ReliantHeart has an International Office located in Uden, Netherlands. IDE Clinical Trial – United States ReliantHeart Inc. is currently conducting an FDA Investigational Device Exemption (IDE) Clinical Trial on the HeartAssist5® Ventricular Assist Device System. The trial is a prospective, 1:1 randomized, multicenter, clinical trial to evaluate the safety and efficacy of 96 patients implanted with the ReliantHeart HeartAssist5® Ventricular Assist Device (VAD) System compared to 96 patients implanted with either a Thoratec HeartMate II® LVAD or HeartWare HVAD for left ventricular support while awaiting cardiac transplantation. The trial is expected to run through 2016. The HeartAssist5® is a device limited by Federal law to investigational use in the United States. CE Mark – Europe ReliantHeart HeartAssist5® Ventricular Assist Device is CE Mark approved for use in patients requiring ventricular support due to end stage heart failure. The HeartAssist5® is approved for bridge to transplant (BTT) patients awaiting cardiac transplantation and for destination therapy (DT) patients who are not candidates for cardiac transplantation. The company's mission is to restore health and extend life of people suffering from heart failure worldwide with the highest quality products possible delivered through exceptional customer service. The DLR Heart – The Revolutionary Alternative to Heart Transplant and Complete Ventricular Systems. The DLR Heart is a key DUALIS developement project. This system has been designed for the long-term support of people with severe cardiac insufficiency. This thoroughly novel technology should give doctors and patients a viable alternative to heart transplantation and complete ventricular systems. DLR Heart, an overview: • Dual chamber system, univentricular and biventricular assistance • Low energy consumption • Efficient support through active control • Long lifespan • Pulsating flow Better Quality of Life for Heart Patients A heart transplant is usually the last option for the approx. 40,000 patients who are today waiting for a donor heart. However, only about 4,500 hearts can be transplanted per year (USA/EUROPE). Artificial ventricular systems could be an effective solution. The devices currently available are often applicable as a support system for the left ventricular chamber only and considerably limit the patient’s quality of life. The development of our innovative, totally implantable DLR Heart for Ventricular Assistance will overcome these limitations. The target lifespan of several years and the wireless power supply allow patients a speedier return to everyday life and maximum quality life in the long term. Investigational Device Only. The World’s Most Gentle System for Lasting Ventricular Assistance. The DLR Heart has a novel bi-chamber technology which enables the patient to keep his/her own heart. The fully implantable ventricular assist system can support both chambers of the heart (biventricular) simultaneously and so renders the transplant of an artificial heart or substitute heart unnecessary. High Tech from Space Research. The hydraulic drive unit technology of the DLR Heart is based on the long-standing development of lightweight construction robots. The mechanical load of the hydraulic components is minimised by liquid storage, and a practically unlimited lifespan is possibe. The pumping chambers of the system are flow optimized, have been improved and further developed in numerous studies. This considerably reduces the risk of thrombus and plaque. Innovative nanocoatings will, in the future, provide for even better biocompatibility. Wireless Energy Supply for Full Freedom of Movement Round-the-Clock. The DLR Heart is powered by our innovative power transmitter system which allows a wireless transfer of data and power to implants. With this, wiring is no longer necessary in the abdominal wall. The patient can move freely. Since 2006, from our location in Seefeld near Munich, we have been supporting our customers with the development of tailor-made systems and products for use in various sectors, from medical technology and the automotive supply industry to consumer electronics and machine and plant construction. With our roots in aeronautics and our extensive network of partners, we ensure that our customers achieve the best possible results. At the same time, we are always ready for lively discussion: as early as the idea stage for a new product, our sales, project management, research and development teams work intensively with our customers. Alongside our development services, we offer you the opportunity to make use of our patent pending technological innovations. These include wireless energy and charging technology, special pumps and drive technology and a range of coatings. We adapt all of our technology to your specifications and integrate it into your system individually based on custom development. The Arrow LionHeart™ Torso of man's body with Arrow LionHeartTM implanted. Click on Image for more information The Arrow LionHeart™ is the first fully implantable heart assist device. The Arrow LionHeart™ is not an artificial heart. It is a "heart helper" or left ventricular assist system (LVAS) for patients suffering from severe heart failure who are not eligible for a natural heart transplant. The Division of Artificial Organs at Penn State College of Medicine, Walter Pae, Jr. M.D.pioneered the development of the Arrow LionHeart™ and has collaborated closely with Arrow International, Inc. in preparing the device for clinical use. Under the direction of Dr. Walter Pae, Jr., professor of surgery at Penn State Milton S. Hershey Medical Center, clinical trials began in Europe in October 1999 and were recently completed. U.S. Trials began in February 2001 and continue today. was implanted for the first time – anywhere in the world – by Prof. Reiner Körfer, MD, Dr. h.c. and his team of specialists at the Clinic for Thoracic and Cardiovascular Surgery within the Heart and Diabetes Center NRW, Bad Oeynhausen, Germany on October 26th, 1999. Unlike previous assist devices, the LionHeart™ system, developed by the American company Arrow International Inc., has no connection to an external power supply. The battery is sewn under the skin and is recharged from the outside by means of induction. This cable-free (and thus wound-free) power supply considerably reduces the risk of infection. The energy storage system within the body functions for 45 minutes without recharging, giving the wearer time to remove the charger belt and take a shower or a swim. Since 1999 a total of 10 patients have received this fully implantable total artificial heart in Bad Oeynhausen. The Levacor VAD™ by WorldHeart The Levacor VAD™ The Levacor VAD™ by WorldHeart is an advanced, next-generation rotary blood pump intended for adults who suffer from late-stage heart failure. Unlike the initial generation of rotary pumps with mechanical or blood-lubricated bearings, the Levacor VAD™ is a compact, centrifugal pump with an impeller that is completely magnetically levitated. Full magnetic levitation eliminates wear mechanisms during operation of the pump. It also permits greater clearances and more optimized blood flow around the impeller while eliminating dependence on the patient's blood for suspension. The Levacor VAD's levitation technology employs a unique combination of passive and single-axis active control, resulting in the simplest levitation system possible. Using this and other innovative technologies, the Levacor VAD™ system is designed to deliver unique benefits High Margin of Safety Enhanced Blood Compatibility Multi-Year Reliability and Durability Easily exchangable wearables Wide Range of Applicability Indications: Transplant, Recovery, and Destination WorldHeart's Novacor® LVAS was approved for use in North America, the European Union and Japan. Sales were discontinued in 2008. WorldHeart's Novacor® LVAS is an implanted, wearable system that provides long-term pulsatile circulatory support for patients with life-threatening heart failure. Since 1984, the Novacor® LVAS has been implanted in more than 1,800 patients, predominantly for a Bridge-To-Transplant indication. Sales of the Novacor LVAS were discontinued in 2008. The field experience and expertise gained by clinical use and commercial sale of the Novacor LVAS in North America, Europe and Japan has been applied to the development of WorldHeart's next-generation rotary blood pumps: Levacor VAD (Above), the MIVAD and the PediaFlow VAD. Founded in 1996, WorldHeart is a public company headquartered in Salt Lake City, Utah (USA), with additional offices located in Oakland, California (USA), and in Herkenbosch (The Netherlands). Its registered office is Delaware, USA. WorldHeart's VADs are used to support the left ventricle, which takes oxygenated blood from the lungs and pumps it to and through the tissues and organs. As a result of this heavy and constant demand, the left ventricle does most of the pumping work and therefore fails more often. Long-term support of the left ventricle alone is estimates to serve more than 80% of eligible patients. In this application, these devices are called LVADs (Left Ventricular Assist Devices). WorldHeart's VADs have been successfully used for the following indications for heart failure patients: Framingham, Mass. and Salt Lake City, Utah, August 2, 2012 – HeartWare International, Inc. (NASDAQ: HTWR), a leading innovator of less invasive, miniaturized circulatory support technologies that are revolutionizing the treatment of advanced heart failure, today announced the closing of the acquisition of World Heart Corporation following the approval of the transaction today by World Heart stockholders. The Impella Devices, AB5000, AbioCor & More by Abiomed The IMPELLA Devices are minimally invasive catheter pumps that can support the heart with up to 5.0 liters blood per minute. The pumps can be implanted percutaneously, via a cut-down, or in the OR. The Impella 2.5 Cardiac Assist Device is a minimally invasive, catheter-based cardiac assist device designed to: Directly unload the left ventricle Reduce myocardial workload and oxygen consumption Increase cardiac output and coronary and end-organ perfusion The Impella 2.5 can be inserted into the left ventricle in a Cath Lab via a standard guidewire through the femoral artery, into the ascending aorta, across the valve and into the left ventricle. The tip of the catheter contains a “pigtail” that crosses the patient’s heart valve and rests in the left ventricle, generating flows up to 2.5 L/min. Impella 2.5 Cardiac Assist Device Now Available to Doctors and Patients in the U.S. June 2, 2008 The U.S. Food and Drug Administration (FDA) just cleared the Impella 2.5 Cardiac Assist Device, the world's smallest heart pump only slightly larger in diameter than a drinking straw, for immediate use. Designed for cardiac arrest and heart attack patients, it pumps up to 2.5 liters of blood per minute, and supports the heart in situations when it cannot function on its own. Each year over a million people in the U.S. have a heart attack, according to the National Institutes of Health. Of that statistic, half of them die and many are left with permanent heart damage. As the world's smallest Ventricular Assist Device (VAD), this technology provides patients with immediate, sustained coronary perfusion when their heart is unable to do so. Today's clearance allows Abiomed to begin selling the device for use to the estimated 14,000 interventional cardiologists at approximately 1,700 heart hospitals in the United States. The Impella CP™ The Impella CP™ is a new percutaneous, catheter-based Impella® device. The increased flow of the Impella CP™ is delivered on the same platform as the Impella 2.5. The pump can be inserted via a standard catheterization procedure through the femoral artery, into the ascending aorta, across the valve and into the left ventricle. The Impella 5.0® The World’s Smallest 5.0 L/min Heart PumpThe Impella 5.0 catheter is an intravascular microaxial blood pump that delivers up to 5.0 L/min of forward flow blood from the left ventricle to the aorta.The Impella 5.0 can be inserted into the left ventricle via femoral cut down or through the axillary artery. The Impella 5.0 pump goes through the ascending aorta, across the valve and into the left ventricle. Micro-Axial Blood Pump Delivers forward-flow from the left ventricle to the aorta 9 Fr catheter-based platform 21 Fr micro-axial pump Minimal bedside support Single Access Point Minimally invasive placement through a single artery and into the left ventricle Several options for access site No septal puncture No priming/no blood outside the body Multiple large bore cannulae not required The Impella® LD pump is a minimally invasive, catheter- based cardiac assist device designed to directly unload the left ventricle, reduce myocardial workload and oxygen consumption while increasing cardiac output, coronary and end- organ perfusion.The Impella LD can be inserted into the left ventricle via open chest procedures. The Impella LD pump is inserted through the ascending aorta, across the valve and into the left ventricle. Micro-Axial Blood Pump Delivers forward-flow from the left ventricle to the aorta is vacuum assisted technology with clear housing to allow clinicians a view into the device. Unlike other ventricular assist systems that can require multiple drivers for a single patient, patients on the AB5000 Ventricle require only a single driver – regardless of condition. The AB Portable Driver is designed to allow patients to leave their hospital rooms and walk within the hospital and on hospital grounds. Multiple studies have shown that patient ambulation, or walking, greatly assists the recovery process. The ease of use and transport capability of the AB Portable Driver makes it an important option for both regional and local cardiac centers. The AB Portable Driver The AB Portable Driver Increased Mobility and Versatility – Without Compromise The AB portable was designed to retain all functionality of the AB5000 Console for AB5000 Ventricle patients. The AB portable console provides biVAD support with adjustable vacuum controls and independent weaning controls. The AB portable is able to support patients from surgical implant through weaning to explantation. Lightweight, Compact, Portable The AB Portable Driver weights 18.9 lbs. Configuring the portable driver with its AB Power Pack and small mobile cart, allows for easier, independent patient ambulation, in-hospital transfer, or land/air transport. Advanced compressor and proportional valve technologies produce an inherently quiet design which minimizes disruption to the patient and their environment. AbioCor Implantable Replacement Heart is the world's first completely self-contained replacement heart. A product of three decades of research, development and testing, the AbioCor is central to ABIOMED's mission to make real the day when heart failure need not mean the end of life or the ability to enjoy life. AbioCor was designed to fully sustain the body's circulatory system. The AbioCor, which is FDA approved under a humanitarian device exemption (HDE), is intended for severe chronic heart failure patients whose normal heart function cannot be restored, are not eligible for transplant, and, according to Abiomed, "have no other treatment options." Although AbioCor is considered to be an engineering marvel, it has a very limited market due to its relatively short life. Next-generation AbioCor II, which is in development, is 30% smaller than AbioCor I and is anticipated to have a life expectancy approaching five years. NOTE: The AbioCor is NOT CE marked and is NOT available in Europe at this time. Abiomed is a global technology leader focused on RECOVERING HEARTS AND SAVING LIVES. (Website) The Company's portfolio of heart support and recovery products and services offer healthcare professionals an array of choices across a broad clinical spectrum. From the catheterization lab to the surgical suite, together with interventional cardiologists and surgeons, Abiomed is dedicated to providing the most advanced medical technologies to heart patients, with the ultimate goal of heart recovery and improved quality of life. Abiomed was founded in 1981 and is the only company in the world with exclusive labeling on ventricular assist devices for all potentially recoverable heart failure indications. The Company develops, manufactures and markets advanced medical technologies designed to assist or replace the pumping function of the failing heart. Abiomed is the global leader for products in the acute heart failure market and ships more ventricle assist devices (VADs) than any other company in the world. The Company is focused on expanding its global distribution, fueling innovation and new products to broaden the Company's product portfolio to become the world's circulatory care leader. Corporate Headquarters: Danvers, Massachusetts European Division: Aachen, Germany Number of Employees: 300+ The Procyrion catheter deployed ventricular assist device (CVAD) The Procyrion System The Procyrion catheter deployed ventricular assist device (CVAD) is deployed percutaneously within the descending aorta and held axiosymmetric within the aorta by a self-expanding strut fixation system. Once the pump is activated, a micro-motor and impeller pulls fluid from the heart and restores body hemodynamics. The pump can then be retrieved through a catheter-based procedure when the heart has had a chance to heal. Restores hemodynamics through continuous aortic flow augmentation Deployed and retrieved in a catheter lab Unloads the heart without invasive surgery and damage to the heart muscle Reduced stroke risk High perfusion of the carotid and coronary arteries (No STEAL phenomenon) High ambulatory patient mobility Potential to treat less sick patients earlier in the heart failure spectrum The HeartMate II and The HeartMate XVE by Thoratec HeartMate II® Left Ventricular Assist System HeartMate II® Left Ventricular Assist System Life Restored. Proven Alternative for Advanced Heart Failure. The HeartMate II, approved by the Federal Drug Administration in January 2010 for use in patients who not only are waiting for a heart transplant, but who want to live with the VAD for the rest of their lives is Thoratec's first-line intermediate-to-chronic left ventricular assist device for Bridge-to-Transplantation and Destination Therapy (i.e. long term support for patient ineligible for cardiac transplantion). Designed to dramatically improve survival and quality of life, the HeartMate II was developed with the goal of providing several years of circulatory support for a broad range of advanced heart failure patients. Its small size and quiet operation make the HeartMate II suitable for a wider range of patients, including women and those of smaller stature. With product attributes specifically developed to minimize the risk of complications, the HeartMate II is exceptionally durable, dependable, and thromboresistant. It offers a range of features and benefits: •Implantation requires a less invasive surgical procedure •Relative ease of management; completely wearable system •Low-dose anticoagulation regimen •Improvement of hemodynamics prior to cardiac transplantation can help optimize long-term outcomes HeartMate® XVE Left Ventricular Assist Device HeartMate® XVE Left Ventricular Assist Device The Only Intermediate-to-Chronic LVAD Requiring No Systemic Anticoagulation The HeartMate XVE (also referred to as HeartMate I) is one of the most widely used left ventricular assist devices in the world. With its low thromboembolic risk, the HeartMate XVE can be used for either Bridge-to-Transplantation or Destination Therapy (chronic support for those ineligible for cardiac transplantation.) It offers a range of features and benefits: •Provides complete unloading of the left ventricle in refractory heart failure patients •Low proven stroke rate Does not require systemic anticoagulation •Improves outcomes of heart transplantation compared to continuous inotropic infusions For more than 30 years, Thoratec has been committed to developing advanced medical technologies to improve patient survival and quality of life. (Website) Thoratec provides the broadest mechanical circulatory support portfolio to treat the full range of clinical needs. From acute to chronic heart failure, Thoratec offers proven device-based therapies to provide a new beginning for patients and their families. Additionally, the company's wholly-owned subsidiary, International Technidyne Corporation (ITC), manufactures and sells a wide range of equipment for hemostasis management and point-of-care testing. Thoratec employs more than 1,000 people worldwide. We are based in Pleasanton, California, with facilities in Burlington, Massachusetts; Rancho Cordova, California; Edison, New Jersey; and Cambridgeshire, UK. In June, 2013 Thoratec acquired the DuraHeart II ventricular assist system from the Japanese company Terumo for an upfront payment of $13 million and potential milestone payments of up to $43.5 million......read more CentriMag Blood Pump & PediVAS Blood Pump by Levitronix CentriMag Blood Pump The Levitronix CentriMag The CentriMag Blood Pump is a bearingless polycarbonate pump designed for extracorporeal blood pumping applications. The CentriMag Blood Pump represents a new generation of blood pumps that provide hemodynamic support with minimal blood trauma. Unlike conventional devices, the CentriMag® Blood Pump does not contain seals or bearings which are components known to cause hemolysis and promote thrombus formation. The Levitronix CentriMag Blood Pump has been used as a ventricular assist device for a wide range of patients worldwide. Key applications include: •Post-cardiotomy failure (failure to wean from bypass) •Bridge to transplant •Bridge to recovery •Bridge to a long-term device •RVAD support with a long-term LVAD •Respiratory (Veno-venous) ECMO •Cardiac (Veno-arterial) ECMO In addition to use as a ventricular assist device, the CentriMag Blood Pumping System has successfully supported adult and pediatric patients suffering from respiratory and cardiovascular disorders as part of an extracorporeal membrane oxygenation (ECMO) circuit PediVAS Blood Pump The Levitronix PediVAS Blood Pump The PediVAS blood pump was developed to fill a growing need among neonatal centers for a reliable 30-day centrifugal blood pump. The PediVAS blood pump is a neonatal version of the CentriMag blood pump which has been used to successfully to treat thousands of patients. The PediVAS blood pump has ¼” tubing connectors which allow the use of small cannulae or small oxygenators. The device is ideally suited for neonatal patients who require a maximum blood flow of less than 1.5 LPM. The PediVAS System is based on the same bearingless technology as the CentriMag System. The PediVAS Pump is CE Mark approved for 30 days of use, and therefore, the PediVAS Blood Pump has the longest intended duration of use of any pediatric plastic blood pump available worldwide. The priming volume of the PediVAS Pump is only 14 ml making it ideal for VAD or ECMO circuits. The PediVAS blood pump is operated by the same hardware as the CentriMag blood pump, and requires only one different component, a neonatal flow probe to enable the system to be used for the smallest patients. The hardware is comprised of three major components: The drive console which allows the operator to control the pump, the motor which generates the magnetic fields that elevate and rotate the pump, and a flow probe which measures the flow delivered to the patient. Levitronix has two generations of Primary Consoles....read more LEVITRONIX is the worldwide leader in magnetically levitated Bearingless Motor technology, specializing in supplying blood pumps to the medical community and ultra-pure fluid handling devices for Microelectronics, Life Science and Industrial applications. Their patented technology permits the motor and magnetic bearing to be combined into a single unit with products that achieve maximum reliability, long life, and the ability to pump precious fluids in the harshest of environments. LEVITRONIX offers the ideal solution for those applications that demand contaminant-free pumping, mixing or fluid control for extended periods in a highly reliable fashion. LEVITRONIX is headquartered in Waltham, Massachusetts and in Zurich, Switzerland. Levitronix is a wholly owned subsidiary of Pharos, LLC. have received CE Mark approval for commercial distribution within the European Union for bridge-to-transplantation, destination therapy, and pediatric indications for use. The bridge-to transplantation indication was originally CE Marked in April 2001 for the DeBakey VAD® and the additional CE Mark indications approval for destination therapy and the DeBakey VAD® Child pediatric indication occurred during the second quarter of 2004. Most recently, both the DeBakey VAD® and the DeBakey VAD® Child Systems completed a design and clinical experience evaluation of the last 5 years of commercial experience for the purpose of re-certification of our CE Mark by our Notified Body. The new CE Mark Certification was issued by our Notified Body in 2006 and is valid through April 27, 2011. MicroMed has commercial distribution of the DeBakey VAD® and the DeBakey VAD® Child to all countries of the European Union, Switzerland and Turkey. The DeBakey VAD® Systems are made up of four major components: •The Pump •The Data Acquisition System •The Patient Home Support System •The Controller and VADPAK®. This illustration shows the individual components of the pump The DeBakey VAD® Pump System includes the titanium pump and inlet cannula, the percutaneous cable, the flow probe, and the outflow graft. The pump is attached to a titanium inlet cannula that is placed into the left ventricle. A graft is connected to the pump outlet and attached to the aorta. The inducer/impeller is the only moving part of the pump. It has six blades with eight magnets hermetically sealed in each blade. The inducer/impeller spins at speeds between 7,500ø12,500 RPM and is capable of generating flow in excess of 10 liters per minute. The components are fully enclosed in a titanium flow tube that has been hermetically sealed. The pump is driven by a brushless, direct current (DC) motor stator that is contained in the stator housing. The pump is attached to a titanium inlet cannula that is placed into the left ventricle. A graft is connected to the pump outlet and attached to the aorta. CDAS (Clinical Data Acquisition System) CDAS (Clinical Data Acquisition System) The DeBakey VAD® Clinical Data Acquisition System is used to monitor the patient and adjust the operating parameters of the DeBakey VAD®. It is designed for use during surgery and while the patient is in intensive care. The system provides power to the unit and is used to adjust the speed of the pump to increase or decrease blood flow. The CDAS also monitors critical patient data, including blood flow rate, speed of pump and power usage. PHSS (Patient Home Support System) PHSS (Patient Home Support System) The Patient Home Support System is designed to provide primary power to the DeBakey VAD® while the patient is stationary for long periods or sleeping and may be used in the hospital or at home. In addition to providing power, it provides a battery backup and charges up to four batteries. Whether in the hospital or at home, MicroMed designed the PHSS to allow patients to sleep or rest without concern about changing batteries. The Patient Home Support System is approximately the size of a small cooler and weighs approximately 10 pounds. The MicroMed DeBakey VAD® Controller Controller and VADPAK The DeBakey VADPAK The MicroMed DeBakey VAD® Controller operates the MicroMed DeBakey VAD® and displays key operating information about the pump including remaining battery life. The Controller also sounds an alarm in the event power is inadvertently disconnected or upon detection of unusual operating conditions. The two batteries in the VADPAK will each power the DeBakey VAD® for approximately two to four hours, giving a combined battery time of approximately six to eight hours. The DeBakey VADPAK The DeBakey VAD® Controller and two batteries are housed in the VADPAK, an ergonomically designed carrying case. Together, the VADPAK, Controller and batteries weigh approximately five pounds, allowing patient mobility and the ability to engage in normal, everyday activities. About MicroMed Cardiovascular, Inc. In 1984, Dr. Michael DeBakey and Dr. George Noon performed heart transplant surgery on NASA-Johnson Space Center (JSC) engineer David Saucier, following a severe heart attack. Six months later, Saucier returned to JSC with the desire to apply spacecraft technology to help people with diseased hearts. As early as 1987, informal meetings began with NASA engineers and Drs. DeBakey and Noon to discuss the design of a low-cost, low-power, implantable ventricular assist device (VAD). NASA began formal funding of the development of the device four years later, bringing outer space technology to inner space applications. In 1996, MicroMed Cardiovascular, Inc. received an exclusive license from NASA to use this rotary blood pump for cardiovascular applications. MicroMed then began the development of the critical support systems that would allow the device (system) to be approved by regulatory agencies and to be utilized in lifesaving applications in humans. European clinical trials of the MicroMed HeartAssist 5® began in November 1998 and CE Mark certification was awarded in April 2001 for both the Adult and Pediatric VADs. The Pediatric VAD received FDA approval under a Humanitarian Device Exemption in February 2004. The U.S. clinical study for the Adult VAD is currently underway. MicroMed's world headquarters and its ISO 13485:2003 certified manufacturing facility is located in Houston, Texas. MicroMed has an international office located in Zurich, Switzerland. Octopus® Tissue Stabilizer and Starfish® Heart Positioner by Medtronic Octopus® Tissue Stabilizer and Starfish® Heart Positioner Medtronic's Starfish®2 and Urchin® Heart Positioners used for Beating Heart Bypass Surgery When your arteries cannot supply enough blood to your heart, your doctor may recommend coronary artery bypass graft (CABG) surgery. One of the most common heart surgeries in the United States, CABG surgery restores blood flow to your heart. Approximately every 10 minutes, someone has beating heart or "off-pump" bypass surgery1. Beating heart bypass surgery is – in simple terms – bypass surgery that is performed on your heart while it is beating. Your heart will not be stopped during surgery. You will not need a heart-lung machine. Your heart and lungs will continue to perform during your surgery. Surgeons use a tissue stabilization system to immobilize the area of the heart where they need to work. Beating heart bypass surgery is also called Off Pump Coronary Artery Bypass Surgery (OPCAB). Both OPCAB and conventional on-pump surgery restore blood flow to the heart. However, off-pump bypass surgery has proven to reduce side effects in certain types of patients. The challenge in beating heart CABG surgery is that it can be difficult to suture or "sew" on a beating heart. The surgeon must use a "stabilization" system to keep the heart steady. The stabilization system consists of a heart positioner and a tissue stabilizer. The heart positioner guides and holds the heart in a position that provides the best access to the blocked arteries. The tissue stabilizer holds a small area of the heart still while a surgeon works on it. Medtronic's Starfish®2 and Urchin® Heart Positioners are designed to position and to hold the heart to give the surgeon easy access to the blocked vessel requiring the bypass graft. The Medtronic Octopus® Tissue Stabilizer minimizes limits the motion of a small area of the heart while the rest of the heart continues to beat normally. This allows the surgeon to perform CABG surgery without stopping your heart and without using the heart-lung machine. For more information go to Medtronic.com Medtronic was founded in 1949 as a medical equipment repair shop by Earl Bakken and his brother-in-law, Palmer Hermundslie. Since then, they've grown into a multinational company that uses technology to transform the way debilitating, chronic diseases are treated. Their first life-changing therapy – a wearable, battery-powered cardiac pacemaker – was the foundation for dozens more Medtronic therapies that use Their electrical stimulation expertise to improve the lives of millions of people. Over the years, Medtronics has adapted additional technologies for the human body, including radio frequency therapies, mechanical devices, drug and biologic delivery devices, and diagnostic tools. Today, their technologies are used to treat more than 30 chronic diseases affecting many areas of the body. The DuraHeartTM System by Terumo Heart Inc. The Magnetically Levitated Pump sets the DURAHEART™ apart from other systems. The DuraHeartTM Left Ventricular Assist System (LVAS) is a third-generation rotary blood pump designed for long-term patient support. It incorporates a centrifugal flow rotary pump with a magnetically levitated impeller to pump blood from the heart around the body. The DuraHeartTM System consists of an implantable Pump and several components that support the function of the Pump. The system is made up of seven main components which include: • Pump • Inflow Conduit • Outflow Conduit • Hospital Console • Controller • Batteries and a Battery Charger In June, 2013 California-based Thoratec (THOR) acquired the DuraHeart II ventricular assist system from the Japanese company Terumo for an upfront payment of $13 million and potential milestone payments of up to $43.5 million. About Terumo Heart, Inc Terumo Heart, Inc is dedicated to the innovation, introduction and advancement of products to improve the quality of healthcare for heart failure patients. Their principal focus is the development, clinical evaluation and commercialization of the DuraHeartTM Left Ventricular Assist System (LVAS). The system is designed to provide long-term circulatory support and address the shortage of donor hearts for cardiac transplantation. Combining patented magnetic-levitation and centrifugal pump technologies, the DuraHeartTM LVAS is expected to decrease complications and improve the lives of patients with severe heart failure. Terumo Heart, Inc. is a wholly owned subsidiary of Terumo Corporation with headquarters in Ann Arbor Michigan. The team is led by Bill Pinon. Temporary Total Artificial Heart by SynCardia Systems Inc. The SynCardia temporary Total Artificial Heart was formerly known as the SynCardia temporary CardioWest™ Total Artificial Heart. The SynCardia temporary Total Artificial Heart Patients in need of the SynCardia temporary Total Artificial Heart are often the sickest of the sick. All other treatments have failed. Both sides of their heart are failing to pump enough blood to sustain their body and vital organs are beginning to shut down. Once implanted, the Total Artificial Heart provides the body with immediate, safe blood flow of up to 9.5 L/min through both ventricles, helping vital organs recover faster. The sooner you regain your strength, the sooner you can be listed for a donor heart. Once stable, Total Artificial Heart patients in the U.S. are listed UNOS Status 1A and moved to the top of the transplant list until a matching donor heart becomes available. In contrast, most ventricular assist device (VAD) patients are listed Status 1A for 30 days and then moved down to Status 1B thereafter. Click here to read about the Freedom™ Driver System The investigational 13.5 lb Freedom™ driver is the world's first wearable driver designed to power the SynCardia temporary Total Artificial Heart both inside and outside the hospital. SynCardia to Host Principal Investigators' Meeting for Freedom® Portable Driver Clinical Study Jan. 25, 2011 On Jan. 31, 2011 SynCardia Systems, Inc., manufacturer of the SynCardia temporary Total Artificial Heart, will host a Principal Investigators' meeting in San Diego for its FDA-approved Investigational Device Exemption (IDE) clinical study of the Freedom® portable driver. Weighing 13.5 lbs, the Freedom driver is the first U.S. portable driver designed to power the Total Artificial Heart both inside and outside the hospital. In addition to the U.S. clinical study, the Freedom driver is CE approved for use in Europe. A total of 27 Total Artificial Heart patients have been supported by the Freedom driver: 10 in the U.S., 14 in Europe and three in Australia. The Freedom driver now accounts for more than 1,700 patient days (4.7 years) worldwide. In the U.S., four patients on the Freedom driver have been transplanted, and two have surpassed the study endpoint of 90 days of Freedom driver support at home....read more Introduction to the Freedom® Portable Driver The Freedom® driver is the world's first wearable portable driver designed to power SynCardia's Total Artificial Heart both inside and outside the hospital. The Freedom driver is CE approved for use in Europe and undergoing an FDA-approved Investigational Device Exemption (IDE) clinical study in the U.S. CAUTION - The Freedom driver is an investigational device, limited by United States law to investigational use. DISCLAIMER: Freedom drivers are always shipped, stored and started up with an orange dummy battery in one battery well to engage the safety locking mechanism that prevents both batteries from being removed. Fill volume and cardiac output in this video are not representative of how the driver is used on an actual patient. SynCardia Systems, Inc. is a private company formed in 2001 to commercialize the SynCardia temporary Total Artificial Heart. Today, with more than 850 implants, the SynCardia Total Artificial Heart is the only FDA, Health Canada and CE approved Total Artificial Heart in the world. Originally used as a permanent replacement heart, the Total Artificial Heart is currently approved as a bridge to human heart transplant for people dying from end-stage biventricular failure. Similar to a heart transplant, the Total Artificial Heart eliminates the symptoms and source of biventricular failure by replacing both failing heart ventricles. Unlike a donor heart, the Total Artificial Heart is instantly available at SynCardia Certified Centers. During the 10-year pivotal clinical study, 79% of patients receiving the Total Artificial Heart survived to transplant. This is the highest bridge-to-transplant rate of any approved device in the world. SynCardia’s Total Artificial Hearts, Drivers and Other Accessories are available 24/7 to World’s Top Transplant Centers via http://shop.syncardia.com/ The Jarvik 2000 FlowMaker® & The Jarvik 7 by Jarvik Heart, Inc. Like the artificial heart, the first ventricular assist devices (VADs) developed 25 years ago were meant to sideline the failing biological heart of a heart failure patient. These pumps were heavy, bulky things that drew blood from the left ventricle through an intake valve and moved it into the aorta at as much as 10 liters per minute — the full output of a healthy heart. Some of the VADs made today take into account the fact that even severe heart failure patients retain partial functioning of the left ventricle: from as little as 10 percent to as much as 50 percent of its normal capacity. The tiny, valveless Jarvik 2000 FlowMaker®, developed by artificial heart pioneer Dr. Robert Jarvik, is one such design. The Jarvik 2000 FlowMaker® is designed to provide reliable support to the ailing heart for a decade or longer. Since accelerated tests of the pump's bearings are not practical, many more years of real-time testing are required to know whether or not the pump will achieve or exceed its design objective. Presently, the Jarvik 2000 has supported one lifetime-use patient since the year 2000, longer than any other device in the world, but its ultimate durability remains unknown. To date, not a single mechanical failure has occurred in any of the more than 200 patients who have received the Jarvik 2000. The Jarvik 2000 pump is about the size of a C battery. Within its welded titanium shell sits a direct-current motor, a rotor supported by two ceramic bearings, and a single moving part: a small, spinning titanium impeller that pumps blood from the heart at up to 7 liters per minute. Rather than take over for the biological heart, the Jarvik 2000 augments the weakened heart's blood output to help restore a normal blood flow throughout the body. Currently, the Jarvik 2000 does not have full FDA-approval. Investigational studies of the Jarvik 2000 are approved by the FDA, but presently only for bridge-to-transplant use. In Europe, the Jarvik 2000 has earned CE Mark certification for both bridge-to-transplant and lifetime use....continue reading Held in the hand, the Jarvik 2000 pump is about the size of a C battery In essence, two types of artificial hearts exist: • the total artificial heart — which is implanted after the natural heart is removed • the ventricular assist device — which is implanted to assist the natural heart, leaving the patient's own heart in place and still functioning. "Removing a person's heart is one of the most dramatic surgical procedures one can imagine," says Dr. Jarvik, who began developing a tiny ventricular assist device, the Jarvik 2000, in 1988. "It is no surprise that more public attention is given to replacing a heart than to assisting one. But consider this question: If you had a failing arm or leg, would you rather have the best-possible artificial limb or a device that allowed you to keep your own arm or leg?" The question is rhetorical. But while ventricular assist devices find wider application in patients than total artificial hearts, experts view the two as complementary treatments. For example, a total artificial heart is required when an assist device will not do, as in cases of biventricular failure when both sides of the natural heart falter. In the 60s and 70s, mechanical hearts were being developed by the National Institutes of Health (NIH) but were largely unknown to the public. Then in 1967, Christian Bernard performed the first human heart transplant, an event that generated worldwide interest: People were suddenly aware of heart replacement as a way to treat a failing heart. In 1969, Denton Cooley performed the first implantation of a temporary total artificial heart, and the primitive device sustained the patient for almost three days until a donor was found through an urgent appeal in the press. After another decade and a half of NIH-supported research, the Jarvik 7 heart became the first total artificial heart implanted as a permanent replacement for a hopelessly diseased natural heart. The Jarvik 7 implantable artificial heart Dr. Robert Jarvik, born in 1946 in Michigan, was a prodigy who invented a surgical stapler and other medical devices while still a teenager. While Jarvik was an undergraduate student at the University of Utah in 1964, his father needed to have surgery for his ailing heart. That family ordeal helped influence Jarvik, who went on to earn his medical degree at Utah, to turn his curiosity, inventiveness and problem-solving skills toward finding a method of saving patients with stricken hearts until they could receive a transplant. While he wasn’t the first to develop an artificial heart, Jarvik’s 1982 creation, the Jarvik 7, was the first such device that could be implanted inside a person’s body. Jarvik continues to work toward the development of a device that could serve as a permanent replacement organ. Though it carries the name of his colleague, Dr. Robert Jarvik, the Jarvik 7 artificial heart was invented by Dr. Willem Kolff. It carried Dr. Jarvik’s name because it was Dr. Kolff’s policy to attach the name of the co-worker who was currently working on any particular model of artificial heart, according to Dr. Kolff’s biographer, Herman Broers, in the book “Inventor for Life” (B & V Media Publishers, 2007). When it came time to implant a heart into a patient, Mr. Broers said, the Jarvik-7 was chosen because it had a multilayer diaphragm, designed by Dr. Jarvik, that proved crucial to the device’s success. But credit for the artificial heart belongs to Dr. Kolff. Jarvik 7 Artificial Heart The First Jarvik 7 Patient In 1982 the Jarvik 7 heart became the first total artificial heart implanted as a permanent replacement for a hopelessly diseased natural heart. At the University of Utah on December 2, 1982, William DeVries, MD implanted the Jarvik 7 total artificial heart into Barney Clark, a Seattle dentist who volunteered to undergo the pioneering procedure because he wanted to make a contribution to medical science. Dr. Jarvik recalls that, before the surgery, Dr. Clark told doctors that he didn't expect to live more than a few days with the experimental heart, but he hoped that what the doctors learned might help save the lives of others someday.....read complete history of The Jarvik 7 total artificial heart Jarvik Heart, Inc. is a private company that develops miniaturized heart assist devices for the treatment of severe heart failure. The company, formed in 1988, is located in Manhattan, where it conducts all development and manufacturing activities. Leon Hirsch, founder and former Chairman of United States Surgical Corporation, serves as Chairman. Robert Jarvik, MD, inventor of the Jarvik 7 and Jarvik 2000 mechanical hearts, is President and Chief Executive Officer. Marilyn vos Savant, columnist for Parade magazine, is Chief Financial Officer. The Jarvik 2000 FlowMaker®, Jarvik Heart's successful pilot heart pump, is an investigational device used in the United States to support patients awaiting heart transplants. In Europe, the Jarvik 2000 has earned CE Mark certification for both bridge-to-transplant and lifetime use. As an investigational device, the Jarvik 2000 has been implanted in more than 200 heart failure patients with no mechanical failures, and has successfully sustained and improved the condition of patients awaiting transplants, as well as those who have chosen the device for lifetime use. INCOR®, EXCOR® and EXCOR® Pediatric by Berlin Heart The INCOR® blood pump is the implantable VAD system made by Berlin Heart. In this system, the pump is implanted directly next to the heart and connected to the heart using short cannulas. The pump is driven electrically. Batteries are used to supply the power and are connected to the pump via a cable. The batteries and control unit are stored in a bag which can be worn comfortably like a belt. * The INCOR® blood pump is not approved for use in the US INCOR Snap In Connector The necessary power to drive the pump is supplied through a cable inserted under the skin on the patient's right side. The cable is connected to a small control unit which monitors and regulates the whole system. A main power pack and a back up power pack are attached to the control unit and supply INCOR® with sufficient electrical current. INCOR® generates a steady blood flow which, in combination with the residual activity of the native left ventricle, leads to reduced pulsatility for the patient. The blood contact surfaces of INCOR® are coated with Carmeda®BioActive Surface. Tilting disc – approved and reliable for long-term applications EXCOR® Blood Pumps – handmade transparent marvel Every EXCOR® blood pump consists of a transparent polyurethane housing that is divided into one air chamber and one blood chamber by a three-layer membrane. Graphite between the membranes helps to minimize friction. The membrane on the blood side merges without a seam into the surface of the housing. A specially produced CARMEDA® coating is plated on the slick, flow-optimised blood contact surface. In- and outflow sockets, which are made of polyurethane and bear titan connectors for the connection of the cannulas, lead from the blood chamber to the in or outlet cannulas. On the air side of the membrane lays the connection for the pneumatic driving tube. The de-airing is effected through the de-airing socket. Polyurethane valve. Operates soundless Pump valves: tilting-disc or polyurethane? Mechanical valves in the sockets ensure an adjusted blood flow. The blood pumps are available with two different types of valves: • Tilting disc – approved and reliable for long-term applications • Polyurethane valve. Operates soundless Selection of EXCOR® Pediatric Blood Pumps The Berlin Heart EXCOR® PediatricBlood Pumps – the paracorporeal ventricular assist device EXCOR® Pediatric has been specially developed for children, infants and even babies. This has been made possible by the wide variety of blood pumps and cannulas we have to offer. EXCOR® Pediatric is a paracorporeal, pulsatile ventricular assist device, or VAD for short. Paracorporeal means that the actual blood pumps are located outside of the body, and are connected to the heart and blood vessels via cannulas. EXCOR® Pediatric can be used to support one ventricle (left-sided / LVAD or right-sided / RVAD) or both ventricles (bilateral / BVAD). The system is used successfully as short, medium and long-term cardiac support. EXCOR® is often used as a bridge until heart transplantation is performed or the heart has recovered. EXCOR® has also been used as an alternative to a heart transplant in some patients. Since its first use in 1987, roughly 2,000 patients have been supported with the EXCOR® device In 1997 the acquisition of the paracorporeal device with the name “Berlin Heart” (now EXCOR®) from the company Fehling Medical AG took place. The Mediport Berlin Heart GmbH Kardiotechnik was founded. In order to make VAD patients independent from hospitals and allow them to live their life with such a device at home, a smaller, mobile driving unit was developed in 1997. The CE approval and introduction to the market followed in 1999. In June 2002 the worldwide first implantation of the INCOR® device took place in the German Heart Centre DHZB. The CE approval for Berlin Heart INCOR® was granted after 9 months of clinical testing on March 21st 2003. Berlin Heart Inc., a wholly owned subsidiary of Berlin Heart AG, was founded in October 2005. A US team is in place to support entry into the US market. The on-site presence ensures optimal support of the US clinics in emergency cases and allows close cooperation with the FDA...website The Totally Implantable Artificial Heart by CARMAT SAS implantable prosthesis and external systems The system is based on an implantable part, a portable part and some external devices dedicated to the electrical feeding of the prosthesis and the monitoring of the patient. The implanted parts include the cardiac prosthesis and the electric connections to the power supply that is bared by the patient. This system contributes to the quality of life of the patient with more mobility and self sufficiency. It is made on one hand of some rechargeable batteries with 4 to 5 hours of autonomy based on the currently available technologies. A second generation, in a final stage of research, should relieve the patient of the burden of recharging the batteries, as the autonomy will exceed 12 hours. On the other hand, a monitoring waist box should provide the patient with useful information and relay the telediagnosis data to the hospital for proper monitoring of the patients with implanted artificial hearts. This 24/7 monitoring service is based on the technologies developed for pacemakers. It monitors internal data related to the prosthesis as well as physiological data originating from the patient. The electrical transfer from the batteries to the prosthesis shall be achieved through a post auricular plug or an induction system. Those systems should prevent the infections due to percutaneous cables. Some external equipments complete this system: a monitoring console in intensive care units shall provide the surgeon with a detailed status of the prosthesis and measured physiological parameters, a battery charger and various connectors to household or cars electrical plugs. Two motor driven pumps (A) suck and inject alternatively a fluid in the ventricular cavities (B) moving the membrane (C)… When the hydraulic compartment is emptied, the membrane sucks the blood inside the ventricle: Diastole (D) - When it is filled, the membrane pumps the blood in the arteries: Systole (E). Biological admission (D) and ejection (E) valves ensure that the blood only flows in one direction. The prosthesis works like a natural heart and is hydraulically activated;an intermediary liquid is used to push the blood into the bloodstream. There are two times in the heart rate: the diastole when the ventricles are filled with blood and the systole when the blood is ejected in the main vessels. The prosthesis is composed of 2 ventricular cavities, left and right, each being separated in 2 volumes with a flexible membrane, one for the blood and the other one for the activating liquid. This membrane reproduces the visco-elastic nature of the cardiac muscle and acts accordingly with the blood and pushes it during the contraction. Two miniature motor driven pumps forward the activating liquid towards the ventricles, generating the systole or by reversing the rotation, towards the external bag, during the diastole. Electronic devices regulate the prosthesis according to the patient’s needs using information generated by sensors and by a microcontroler. An external bag carries the activating liquid and pulses in unison with the cardiac rate. The internal layout of the artificial heart was regularly optimised. Engineers worked hard on designing the different elements to keep the ventricular volume as important as possible and by doing so, to insure a good blood flow without artificially increasing the functioning frequency. The prosthesis is connected to the patient’s atrium with a special interface system allowing an easy suture on which the prosthesis is clicked. Created in June 2008, CARMAT SAS is an innovative medtech start-up financed by TRUFFLE CAPITAL, EADS and Professor Carpentier with additional funding from the French state innovation agency OSEO. CARMAT has developed a totally implantable artificial heart which features the left and right ventricles. Its hi-tech design seeks to make the device as similar as possible to the human heart. The CARMAT project has been spun off of the collaboration between Professor Carpentier and EADS on implementing biomaterials and cutting-edge technologies in the artificial heart field. The project is based on 15 years of development experience. The TandemHeart by CardiacAssist, Inc The TandemHeart Pump acts with the THTC-EF Cannula to unload the left side of the heart TandemHeart System Overview The TandemHeart System is comprised of three sub-systems. The TandemHeart Pump provides the circulating power to pull oxygenated blood from the left atrium and to return it to the systemic arterial circulation. By way of two percutaneous access points in the patient's groin, the TandemHeart Cannula Set connects the Pump to the body. The TandemHeart Controller provides operating power to the Pump, provides a controlled flow of lubricant to the Pump, and also provides automatic system monitoring and alarms indicating conditions that require attention. CardiacAssist, Inc. is a Pittsburgh, PA based medical device company that develops, manufactures and markets cardiac assist devices. The company, formed in 1996, has developed a unique and proprietary platform technology to provide a short-term circulatory support system for cardiologists and cardiac surgeons. •Deliver novel solutions that reduce health care costs and improve patient outcomes. •Provide products to the cardiologist and cardiac surgeon that address a broad range of patients less invasively and improve response time for patients to receive effective heart support in the cardiology cath lab. While drug treatment can provide support for patients experiencing acute heart failure, some do not respond to maximum medical therapy with or without IABP (intra-aortic balloon pump) treatment. There is growing evidence to suggest that earlier deployment of mechanical circulatory support is a critical determinant of success. Cardiologists and cardiac surgeons are therefore searching for novel treatment solutions to reduce the high incidence of morbidity and mortality for profound heart failure patients through: •Earlier institution of circulatory support •Minimally invasive approaches CardiacAssist, Inc. is dedicated to providing innovative products to satisfy these requirements. VentrAssist by Ventracor Ltd VentrAssist left ventricular assist device (LVAD) is an implantable blood pump designed as a permanent alternative to heart transplantation for people suffering congestive heart failure. It can also provide temporary therapy while patients wait for a transplant. The device addresses the growing health problem of heart failure, for which the only cure is a heart transplant. According to Ventracor there are an estimated 11.2 million sufferers of congestive heart failure worldwide, a total that is increasing by 10 per cent each year. Only about 3000 people receive a heart transplant each year. The VentrAssist is a blood pump that connects to the left ventricle of the heart to help its pumping function. The procedure does not require the removal of the patient's heart, and the pump allows it to rest and possibly recover. The pump has only one moving part, a hydrodynamically suspended impeller, that is designed never to wear out or damage blood cells. The device is made of titanium and the inside surfaces are diamond (carbon) coated. It weighs 298 grams and is less than 6cm in diameter, making it suitable for implant in adults and children. When implanted, the pump is connected through the abdomen by the lead to the external controller which contains the battery. The VentrAssist can be used as either a 'bridge to transplant' (BTT) therapy or 'destination therapy' (DT) device. The VentrAssist technology is unique and when first developed was smaller, lighter and simpler than other heart pump devices. The pump's only moving part is a rotating impeller which 'floats' in the blood, reducing wear and potential for blood clots. The VentrAssist helps the heart to pump blood and does not require removal of the heart, providing the possibility for it to rest and recover. The pump is connected to an external controller and power source through a lead in the abdomen. Designed and developed in Australia, the VentrAssist was first patented in 2001. The first human implant was made in June 2003 at The Alfred Hospital in Melbourne. By 2008, more than 250 implants had been made in 36 centres across ten countries. At this time the product had achieved CE Mark approval to market in Europe, TGA market approval in Australia, and was undergoing FDA trials in the USA....read more The VentrAssist was developed by the Faculty of Engineering at University of Technology, Sydney and MicroMedical Industries (later known as Ventracor) over the period 1997-1999. A large team of biomedical experts developed the device based on an original invention by John Woodard (MicroMedical), Peter Watterson (UTS) and Geoffrey Tansley (UTS/MicroMedical). Initial funding for the VentrAssist was received from AusIndustry as an R&D Start Grant. Animal trials were undertaken from 2000 to 2002, and the first human implant was made in June 2003 at The Alfred Hospital in Melbourne. Extensive clinical trials were undertaken, initially in Australia and later in Europe and the USA. Market approval was received in Europe in 2006 and Australia in 2007, and trials continued in the US in 2008. C-Pulse Heart Assist System by Sunshine Heart The C-Pulse Heart assist system is designed to treat clinical symptoms associated with Class III and ambulatory Class IV heart failure. These symptoms normally include shortness of breath, dizziness, low blood pressure and fluid retention. Patients associated with Class III and ambulatory Class IV heart failure are typically unable to engage in normal activities, compromising their quality of life. The C-Pulse Heart Assist System may be implanted through a minimally invasive or full sternotomy technique. C-Pulse® has the potential to revolutionize the treatment of Class III and ambulatory Class IV heart failure. It uses counterpulsation technology to increase cardiac output, coronary artery blood flow and reduce the heart’s pumping workload. • C-Pulse® is a therapeutic approach to treating heart failure and is currently an investigational device undergoing clinical evaluation. The C-Pulse Cuff is placed around the ascending aorta, above the aortic valve. Image from Sunshine Heart. The C-Pulse System’s design is based on proven balloon counter-pulsation technology to assist the heart by reducing the workload of the left ventricle. During inflation of the balloon, blood flow is increased to the coronary arteries, thereby providing additional oxygen which is vital to a failing heart. During deflation, the workload or pumping required by the left heart is reduced. The balloon inflation and deflation is synchronized to the patient’s ECG, similar to a pacemaker. Potential benefits of the technology, which are currently being analyzed in clinical trials, are relief of shortness of breath, increased physical activity, and improved cardiac function. The C-Pulse is designed to improve heart function in three ways: • More blood flow from the heart called increased cardiac output • More oxygen to the heart muscle, called increased coronary blood flow • Less work for the heart, called decreased afterload Image from Sunshine Heart The C-Pulse System may be implanted via a small pacemaker like incision through the ribs (mini-thoracotomy) and sternum (mini-sternotomy) or through a traditional full sternotomy. The anticipated stay in the hospital may be between 4-14 days. Several patients currently enrolled in the Company’s FDA approved IDE feasibility trial have been able to return home in as little as four days when the procedure has been performed minimally invasively. The implant part of the procedure is typically performed in an hour. The cuff portion of the C-Pulse Device is placed around the ascending aorta, and outside the patient’s bloodstream. Because of this, the risk of stroke and blood clots is potentially reduced. There is also no need for patients to take anti-clotting medications such as heparin or warfarin while implanted unless other medical conditions require this. Because of these features, the procedural and device patient risks may be lower when compared to other currently approved Class III/IV mechanical circulatory assist technologies. The C-Pulse can be temporarily disconnected. Patients have expressed satisfaction in being able to shower, take a walk and perform other activities independent from the system. For more information and Patient Brochure Click here Sunshine Heart focuses on an innovative cardiac assist therapy to treat heart patients who represent a large and under-served market segment and provide a significant opportunity for the company. Unfortunately, these Class IV patients, despite optimal drug therapy, have persistent symptomsand their options are very limited. Surgical approaches usually involve complex open-heart surgery or heart transplantation....read more The BiVACOR® System The BiVACOR™ is a device designed to support or totally replace a failing heart. BiVACOR® is a major advance upon earlier generation artificial heart technologies which push blood from one side of the heart only. BiVACOR® can support both sides of a failing heart (BV Assist) or may act as a total artificial heart replacing the heart completely (BV Replace). The core technology for this unique pump relates to the inclusion of left and right impeller vanes positioned on a common rotating disc. The device uses MAGLEV technology to completely suspend and rotate this disc, which affords it the unique ability to respond to a patient’s changing needs by dynamically altering its impeller position, to safely pump blood from both sides of the heart. BiVACOR BV Assist – Designed to support the failing left and right heart The key success factors for an implantable biventricular device are that it is small; reliable; and has a balanced blood flow. No device until now has met all these criteria. The notable design advantages of the BiVACOR® device that will account for its success are that it: BiVACOR BV Replace – Designed to replace the ventricles of a totally failing heart 1. Is a single rotary pump that can assist or totally replace both sides of the heart; 2. Can be used for a bridge to recovery, bridge to transplant, or destination therapy; 3. It is small enough to implant in an 8 year old child, but powerful enough to support an adult; 4. Can simultaneously pump more than 8 l/min from both the left and right sides; 5. Only has one moving part (the central impeller), which is totally suspended inside large clearances using MAGLEV technology; 6. Has no contacting or rubbing components, so there is no wear, making it both reliable and durable (estimated potential life span of more than 10 years); 7. Automatically controls and balances blood flow in both cavities, with the movable impeller; 8. Can be powered across the skin with TET technology, maximising patient mobility and reducing infection; 9. Will be available ‘off the shelf’ so there is no wait for a compatible donor heart; 10. Can provide patients ineligible for transplant a treatment option. BiVACOR® is a privately held company that was founded in 2008 and is based at The Prince Charles Hospital, Brisbane, Australia. A contingent of 6 highly qualified staff has worked diligently toward the development of this ground breaking technology. They include highly experienced and world class biomedical engineers, medical specialists and business executives, as well as support staff. Together they have set up a strong collaborative network which branches out both nationally and internationally. In addition, BiVACOR has engaged assistance from best of breed legal, financial and intellectual property specialists. The BiVACOR® Total Artificial Heart featured in the 60 Minutes story “The Ultimate Bypass”, aired on September 24, 2010. The Ultimate Bypass SmartHeartT Left Ventricular Assist Device and the SmartHeartT Total Artificial Heart by Cleveland Heart Inc. The SmartHeartT LVAD. The SmartHeartT LVAD is comprised of an implanted centrifugal blood pump which is placed in the patient's chest below the heart. The pump takes blood from the patient's left ventricle via a titanium inlet cannula and returns it to the ascending aorta via a coated Dacron graft. The implanted pump is fabricated from titanium with a biocompatible coating applied to a portion of the blood-contacting surfaces. A power cable extends from the implanted pump through the skin to an external controller which powers the pump and regulates pump speed. The SmartHeartT LVAD's elegant, simple design is intended to provide long term reliability and minimize complications. The pump's rotor, it's single moving part, turns on a hemodynamic bearing, a thin film of blood which supports and stabilizes the spinning rotor, obviating the need for mechanical bearings or other wear elements. This feature combined with the optimized blood flow path allows for minimal on-going anticoagulation. Since this design does not require active magnetic stabilization, the percutaneous power cable is small and flexible, minimizing exit site infections. The pump's small profile and integrated inlet cannula provide for intra-thoracic placement even in patients of small stature, reducing placement time and minimizing surgical complications.....read more SmartHeartT Total Artificial Heart: The SmartHeartT TAH is designed to replace the function of the native heart, supporting both systemic and pulmonary circulation. It is based on the design of the SmartHeartT LVAD, in which a single moving part the rotor, is supported in a blood-lubricated fluid film bearing, resulting in a small, simple, reliable device. A single motor drives two centrifugal pumps on both ends of the same shaft. An integrated pressure regulating valve automatically balances left and right circulations without the need for a second motor, sensors and associated cables, connectors, electronics and software. Unlike earlier generations of total artificial hearts, the SmartHeartT TAH's compact size allows for a broader range of patients to be implanted. The TAH shares basic design concepts with the SmartHeartT LVAD: Find out The SmartHeartT TAH About Cleveland Heart Inc. Cleveland Heart, Inc. has partnered with the Cleveland Clinic to develop the next generation of mechanical cardiac circulatory assist devices with the potential to provide a complete range of treatment options for patients suffering from irreversible end-stage heart failure. • Boston Scientific: Mission: to improve the quality of patient care and the productivity of health care delivery through the development and advocacy of less invasive medical devices and procedures. • St. Jude Medical The St. Jude Medical product portfolio includes implantable cardioverter defibrillators (ICDs), cardiac resynchronization therapy (CRT) devices, pacemakers, electrophysiology catheters, mapping and visualization systems, vascular closure devices, heart valve replacement and repair products..... • Edwards Lifesciences Edwards is the leader in the development of new, experimental technologies designed for the non-surgical repair or replacement of heart valves. These transcatheter heart valve technologies would allow clinicians to repair or replace heart valves through a catheter, eliminating the need for open-heart surgery.... • Sorin Group A pioneer and leader in heart valve innovation for more than 40 years, Sorin Group, formerly known as ELA Medical, offers the most complete portfolio of bioprosthetic valves, mechanical valves, and repair products.... • Zoll Medical ZOLL defibrillators and AEDs are available in many models and with hundreds of customizable features, functions and languages to address the unique needs or organizations and clinicians everywhere.... Automated External Defibrillators (AEDs): Portable and automatic, these devices help restore normal heart rhythm to patients in cardiac arrest. They analyze heart rhythm and can help rescuers determine whether a shock is needed to restore a normal heartbeat. Cardiac Ablation Catheters: Long, thin flexible tubes that are threaded into or onto the heart, cardiac ablation catheters treat abnormally rapid heartbeats that cannot be controlled with lifestyle changes or medications. They work by modifying small areas of heart tissue that are causing abnormal heart rhythms. Cardiac Angioplasty Devices: These are long, thin, flexible tubes that are threaded into a heart blood vessel to open narrowed or blocked areas. They improve blood flow to the heart, reduce chest pain, and treat heart attacks. Cardiac Pacemakers: Small and battery-powered, pacemakers are implanted permanently into the body. Used when the heart beats too slowly or has other abnormal rhythms, they monitor the organ's electrical impulses and, when needed, deliver electrical stimuli to make it contract in a more normal tempo. Implantable Cardioverter Defibrillators (ICDs): These monitor heart rhythms and deliver shocks if dangerous rhythms are detected. Many record the heart's electrical patterns whenever an abnormal heartbeat occurs, allowing doctors to review the patterns. New monitoring devices allow ICDs to transmit basic information to physicians. Prosthetic (Artificial) Heart Valves: Used for replacing diseased or dysfunctional heart valves, these are available in two forms. Mechanical valves are made of man-made materials and can usually last a lifetime. Biological valves are made from tissue taken from animals or human cadavers. Stents: Small, lattice-shaped, metal tubes that are inserted permanently into an artery, stents help improve blood flow. Some contain drugs that reduce the chance that arteries will become blocked again. Lindbergh and Carrel on the cover of Time magazine with The Lindbergh organ perfusion pump Charles Lindbergh’s Artificial Heart Just a few years after his historic solo flight across the Atlantic, the aviator developed an ingenious predecessor to today’s man-made hearts. On a shelf in a largely ignored basement display case at Rockefeller University sit a variety of medical devices that have been produced by that institution’s laboratories over the past half century. One of them is especially awkward looking —a glass cylinder that rises two feet before sprouting a seemingly haphazard array of tubes. Its glass innards of more tubes and smaller chambers suggest the workings of some unidentifiable life-form. It was alive once, in a manner of speaking. It is the world’s first artificial heart, unveiled fifty years ago with the publication of an article in Science magazine by its inventor, Charles A. Lindbergh, the man who became an instant hero in 1927 with his flight across the Atlantic. Descendants of the Lindbergh heart—in spirit if not direct lineage—have kept alive a handful of patients with diseased hearts in recent months. The heart worked in connection with a sophisticated rotating valve, a thick disk enclosed in glass, with a tunnel bored through its diameter and two concavities of different sizes carved out of its circumference. The valve rotated in precise imitation of the systolic and the diastolic pressure that the beating of a natural heart exerts on arteries. One of Charles Lindbergh's glass perfusion pumps “That valve was an incredible piece of ingenuity,” reflects Merrill Chase, professor emeritus at Rockefeller University. Chase is the only living witness to Lindbergh’s four-year struggle to perfect the heart for the brilliant and controversial French surgeon Alexis Carrel, who was a staff member of what was then called the Rockefeller Institute for Medical Research. “The pump was a beautiful machine, but this was its key. Without the alternating pressure Carrel just couldn’t have studied organs with any degree of meaning.” Lindbergh’s heart was never meant to be placed in a body; rather it was designed to keep organs alive for an indefinite period outside the body, and Lindbergh referred to it as a perfusion pump. The New York Times called it an artificial heart, and the name stuck. Time magazine described it as “a twist of vitrified bowel oozing out of a clear glass bottle.” Far bulkier than the Jarvik 7 in use today, it looked in profile like an abstract sculptor’s interpretation of a heron....read more The Mayo-Gibbon heart-lung machine was built in 1957 and was among the first machines to act as a beating heart during surgery. Image: National Museum of American History The Mayo-Gibbon heart-lung machine The most well-known of the early artificial hearts is probably the Mayo-Gibbon heart-lung machine, which was first designed by John Gibbon in the late 1940s and later refined by doctors at the Mayo Clinic in Minnesota. Though it looks more like a dining cart, the hulking metal device, which measures nearly six feet tall and three feet wide, was the first machine to act as a beating heart during surgery. It’s covered in knobs and gauges, and the tall accordion-like part you see on top is actually acting as the lung, oxygenating the blood as it flows through the body, allowing doctors to operate in a “dry field.” The Dodrill-GMR artificial heart was made in 1952 by General Motors, which explains why it looks like a V8 motor. Image: National Museum of American History Dodrill-GMR Mechanical Heart In its 100-year history, General Motors has made significant contributions to society extending far beyond the automobile industry. One of these important contributions was the development of the first mechanical heart pump in 1952. Dr. Forest Dodrill, a surgeon at Wayne State University's Harper Hospital in Detroit, believed that a machine could be developed to temporarily replace the human heart's blood-pumping function and make open heart surgery possible. Dr. Dodrill and his medical team called on a group of scientists and engineers at the GM Research Laboratories for help. That unique collaboration resulted in the Dodrill-GMR Mechanical Heart, built by GM Research Laboratories in the public interest and funded in part by the American Heart Association. Measuring 10 by 12 by 17 inches, the invention looked similar to a 12-cylinder engine with six separate chambers. Made of stainless steel, glass and rubber, the mechanical heart used air pressure and vacuum pumps to circulate blood from the chambers through the patient's body while open heart surgery was being performed. In the fall of 1952 the heart pump was first used successfully during a surgery performed on a 41-year-old man. The operation lasted 80 minutes and the mechanical heart was used for 50 minutes to keep the patient alive while his heart was repaired. "We've come a long way since that first heart operation by Dodrill in 1952. Now, it's estimated that worldwide more than one million open heart operations are done using some form of heart-lung machine each year," said Dr. Larry Stephenson, Wayne State University cardiothoracic surgeon and medical historian, in a press release in 2002. "Without some form of blood pump or heart-lung machine, many of the heart operations we routinely do would not be possible. "The success of the Dodrill-GMR Mechanical Heart began a wave of research and medical advances that continue to this day. The original model of the Dodrill-GMR Mechanical Heart is now on display at the Smithsonian Institution Haskell Shanks of Warren leaves Sinai Hospital in Detroit, becoming the first patient sent home with a partial artificial heart, on Sept. 18, 1971. Michigan history: Heart booster gets ticking in Detroit Posted: August 7, 2011 Forty years ago this week, medical history was made in Detroit. On Aug. 11, 1971, a permanent, partial artificial heart was implanted in Haskell Shanks, a 63-year-old former security guard from Warren, in an operation at Sinai Hospital in Detroit. Shanks became the first person in the world to have an artificial heart implanted and go home to live a normal life. Shanks suffered from congestive heart failure and had suffered three heart attacks in the four years before the surgery. The six-inch, rubber-and-Dacron pump affixed to his aorta was called a patch booster and designed to do half the work of his own heart. Leading the eight-man surgical team during a 10-hour operation that cost $25,000 was the famed Dr. Adrian Kantrowitz, who had completed the first human heart transplant in the U.S. four years earlier in New York. At the time, doctors envisioned a day when permanent artificial hearts would come with their own power sources, such as radioactive isotopes or "biological fuel cells extracting sugar from the body." Shanks was released from the hospital five weeks after the operation. He was readmitted Oct. 4 with a chest infection and died Nov. 11 of kidney failure. Kantrowitz, who moved a 25-member team from New York to Detroit when he joined Sinai in 1970, remained in Michigan for the rest of his career. He taught at the Wayne State University School of Medicine and died in 2008 in Ann Arbor. A little humor from the Scientists at Leads University Click Here to read about Heart Pump Systems latest news Any medical information published on this website is intended purely as a informational tool only and is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. The Copyright of all images and documents is by the According Developing Group, Institute, Editor or Company. We only included data and images freely accessible. We have linked each image and/or story back to it's original source. If you want your system or certain information on it removed from our website, please contact us at [email protected]	2	40	2	0	0	0	0.849021	2	18,894
by Jackie Miller, RHIA, CPC Coding biliary procedures requires in-depth knowledge of anatomy as well as coding guidelines. This article outlines the correct coding for biliary procedures in outpatient and physician settings. The Biliary System The biliary system consists of the organs and structures that secrete and transport bile, including the liver, gallbladder, and bile ducts. Interventional radiologists can perform diagnostic imaging of the biliary system as well as procedures for relief of biliary obstruction. Bile is secreted by the liver and drains into small ducts called intrahepatic biliary radicles. The radicles on the right and left sides of the liver drain into the right and left hepatic ducts. The two hepatic ducts then join to form the common hepatic duct. The gallbladder is a sac-like structure that stores and concentrates bile. Bile drains from the gallbladder through the cystic duct. The cystic duct joins with the common hepatic duct to form the common bile duct, which empties into the duodenum. Obstruction of the biliary system can be caused by calculi (gallstones), cancer, infection, cirrhosis, trauma, or other factors. Biliary obstruction needs to be treated promptly because it can cause pain, jaundice, infection, and tissue damage. The Biliary System Diagnostic imaging of the biliary system is performed by passing a needle through the liver into one of the intrahepatic bile ducts. Contrast is then injected into the bile duct under fluoroscopy. This procedure is known as a percutaneous transhepatic cholangiogram (PTC). It is reported with CPT codes 47500, Injection procedure for percutaneous transhepatic cholangiography, and 74320, Cholangiography, percutaneous, transhepatic, radiological supervision and interpretation. Modifier 26, Professional component, must be added to 74320 and all other supervision and interpretation codes discussed in this article when the supervision and interpretation code is reported by a physician who provided only the professional component; for example, when the exam is performed in the hospital setting. Diagnostic imaging studies can also be performed on patients who have a biliary drainage catheter in place. For example, a surgeon may leave a T-tube (a self-retaining drainage tube shaped like a T) in place at the time the gallbladder is removed, and the interventional radiologist may be asked to perform an imaging study via the tube to confirm that there are no remaining gallstones. In other cases an imaging study may be performed on a nonsurgical patient who has had a drainage catheter placed percutaneously due to biliary obstruction. In these situations the radiologist can perform a cholangiogram by simply injecting contrast into the existing tube or catheter. This procedure is often referred to as a T-tube cholangiogram. It is reported with codes 47505, Injection procedure for cholangiography through an existing catheter (e.g., percutaneous transhepatic or T-tube), and 74305, Cholangiography and/or pancreatography; through existing catheter, radiological supervision and interpretation. Biliary Drainage Procedures Interventional radiologists commonly perform three types of biliary drainage procedures. External biliary drainage is performed by positioning a drainage catheter in the bile duct above the obstruction. The physician punctures the skin and passes a needle into one of the bile ducts. The needle is exchanged over a guidewire for a catheter, and the catheter is positioned and sutured in place. All of the bile then drains out of the body through the catheter into a collection bag. Sometimes two separate catheters are used to drain the right and left biliary ductal systems. External biliary drainage is reported with codes 47510, Introduction of percutaneous transhepatic catheter for biliary drainage, and 75980, Percutaneous transhepatic biliary drainage with contrast monitoring, radiological supervision and interpretation. Internal-external biliary drainage procedures are performed to allow bile to drain past an area of obstruction. The physician punctures the biliary tract percutaneously and advances a catheter down the bile duct past the obstruction. The catheter is exchanged over a guidewire for a biliary drainage catheter, which is left to external gravity drainage. Often the external end of the catheter can be capped after a few days so that all the bile drains internally (into the duodenum). Internal-external biliary drainage is reported with codes 47511, Introduction of percutaneous transhepatic stent for internal and external biliary drainage, and 75982, Percutaneous placement of drainage catheter for combined internal and external biliary drainage or of a drainage stent for internal biliary drainage in patients with an inoperable mechanical biliary obstruction, radiological supervision and interpretation. Internal biliary drainage is performed in patients with chronic biliary obstruction, especially those with obstruction due to cancer that cannot be treated surgically. The radiologist places an internal biliary stent, a segment of plastic or metal tubing, into the narrowed area of the bile duct. The stent is completely internal; that is, no part protrudes outside the patient’s body. An internal stent may be placed as an initial procedure, or it may be placed after the patient has had an external or internal-external drainage catheter in place for a period of time. There are several potential coding scenarios for placement of an internal biliary stent. Code 47801, Placement of choledochal stent, is frequently used for this procedure. Code 47556, Biliary endoscopy, percutaneous via T-tube or other tract; with dilation of biliary duct stricture(s) with stent, also incorporates placement of an internal biliary stent. However, code 47556 is defined as an endoscopy procedure, and an endoscope is typically not used for stent placement when the procedure is performed by interventional radiologists. Additionally, the American Medical Association has advised, “It is not appropriate to report an endoscopy CPT code (e.g., 47555) when a nonendoscopic procedure is performed.”1 It should be noted that code 47801 is classified by the Centers for Medicare and Medicaid Services as an inpatient-only procedure. The imaging guidance for placement of an internal stent without bile duct dilation is reported with code 75982. If bile duct dilation is also performed, the guidance should be reported with code 74363, Percutaneous transhepatic dilation of biliary duct stricture with or without placement of stent, radiological supervision and interpretation. Diagnostic Cholangiogram with Drainage Frequently a diagnostic cholangiogram will be performed prior to insertion of a biliary drainage catheter or stent. If a medically necessary diagnostic cholangiogram is performed and documented, both the cholangiogram and the drainage procedure should be coded. When a PTC is followed by placement of an external or internal-external biliary drainage catheter, modifier 59 should be applied to the cholangiogram codes (47500 and 74320) to indicate that they represent a separate diagnostic procedure rather than the imaging used to insert the drain. Currently there are no Correct Coding Initiative edits for PTC performed in conjunction with placement of an internal biliary stent, so modifier 59 is not required in this situation. Multiple Drainage Catheters According to the Society of Interventional Radiology, if the radiologist places two drainage catheters via separate punctures to drain the left and right biliary ductal systems, two drainage procedures should be reported.2 Depending on payer policy, it may be necessary to append modifier 59 or 51 to the second drainage procedure code. Modifiers RT and LT should generally not be used in this situation because most payers do not recognize these codes as bilateral. Often an external or internal-external drainage catheter is converted to a completely internal stent once the patient’s biliary system has decompressed. Biliary drainage procedures (47510, 47511, and 47801) have a 90-day Medicare global period for physician billing. If a staged procedure is performed during the global period of the original procedure, modifier 58, Staged or related procedure or service by the same physician during the postoperative period, should be applied to the CPT code for the second procedure. For example, if a patient undergoes internal-external drainage (47511) followed one week later by internal stent placement (47801), the physician should apply modifier 58 to the stent placement code (47801-58). Because global surgical periods do not apply to hospital billing, no modifier is typically needed on the hospital’s claim for the stent placement. Removal and replacement of an external or internal-external biliary drainage catheter is reported with codes 47525, Change of percutaneous biliary drainage catheter, and 75984, Change of percutaneous tube or drainage catheter with contrast monitoring (e.g., genitourinary system, abscess), radiological supervision and interpretation. Removal and replacement of a T-tube is reported with code 47530, Revision and/or reinsertion of transhepatic tube, and 75984. When a patient presents for a scheduled tube change, a diagnostic cholangiogram is not typically reported. However, if a medically necessary diagnostic cholangiogram is performed and documented, and the decision to replace the drainage tube is based on the results of the cholangiogram, then both the cholangiogram and the tube change can be reported. This most often occurs when the patient presents for evaluation of a nonfunctioning drainage tube, rather than in conjunction with a routine tube change. There is no code for removal of an external or internal-external biliary catheter. For physician billing, the catheter removal is included in the insertion when the catheter is removed during the 90-day global period. For hospital billing, it may be appropriate to report a low-level clinic visit code for the encounter during which the tube is removed, depending upon the hospital’s visit classification criteria. - American Medical Association. Handout for the CPT 2005 Coding Symposium. Chicago, IL. 2004, page 1. - Society of Interventional Radiology. Interventional Radiology Coding Users’ Guide, 14th ed. Fairfax, VA: SIR, 2007. American Medical Association. CPT 2008. Chicago, IL: AMA, 2007. Covey, Anne M., and Karen T. Brown. “Palliative Percutaneous Drainage in Malignant Biliary Obstruction, Part 1: Indications and Preprocedure Evaluation.” Journal of Supportive Oncology 4, no. 6 (June 2006): 269. Available online at www.supportiveoncology.net/journal/articles/0406269.pdf. Covey, Anne M., and Karen T. Brown. “Palliative Percutaneous Drainage in Malignant Biliary Obstruction, Part 2: Mechanisms and Postprocedure Management.” Journal of Supportive Oncology 4, no. 7 (July/August 2006): 329. Available online at www.supportiveoncology.net/journal/articles/0407329.pdf. Jackie Miller ([email protected]) is senior consultant at Coding Metrix in Powder Springs, GA. "Outpatient and Physician Reporting of Biliary Procedures" Journal of AHIMA	4	8	24	0	0	0	0.448181	24	2,499
Documentation of chronic kidney disease (CKD) and its stage are crucial for correct coding, which affects hospital revenue and severity of illness classification. Precise diagnosis and reporting of CKD stage improve the accuracy of our national health care database used for research and for projections of national health care needs. The 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease published by the National Kidney Foundation (NKF) is the authoritative, consensus standard for the diagnosis, classification and management of CKD. The guideline identifies five stages of CKD (listed in Table 1), which are defined by either glomerular filtration rate (GFR) decreased to less than 60 mL/min/1.73 m2 or by presence of certain kidney damage markers (listed in Table 2) for more than three months. The diagnosis of CKD stage 1 or 2 requires the presence of one or more of the markers of kidney damage. Therefore, a patient with a GFR greater than or equal to 60 mL/min/1.73 m2 does not have CKD if there are no markers of kidney damage. Stages 3, 4, and 5 are based on GFR cutoffs alone, although such patients may also have markers of kidney damage. Lab reports of creatinine values typically include the calculated GFR for both African-American and non-African-American patients. The calculated GFR is proportional to serum creatinine but also depends on age, race, and gender. The NKF recommends using the CKD-EPI Creatinine Equation, published in 2009, to estimate GFR (available on the NKF website). It is not necessary to perform a 24-hour urine collection to measure creatinine clearance, even though this may be a more precise measure of GFR if done correctly. The stage of CKD can only be correctly assigned when GFR and therefore creatinine levels are at a stable baseline. Staging cannot be performed when the creatinine is in flux, such as during an inpatient admission. Renal function must be stabilized before staging. The currently preferred clinical terminology of “chronic kidney disease” or CKD should be used in diagnostic documentation. Clinicians should avoid nonspecific, imprecise terminology such as “renal insufficiency” or “chronic renal insufficiency (CRI)” as the correct codes for CKD will not be assigned. End-stage renal disease (ESRD) represents the culmination of progressive stage 5 CKD. It has been a long-standing clinical practice to classify patients with CKD who require either dialysis or transplantation as ESRD. However, ICD-10-CM defines ESRD (code N18.6) as “dialysis-dependent stage 5 CKD.” Dialysis dependence means that the requirement for dialysis is expected to last three months or more. A significant conflict exists between the clinical documentation standards and ICD-10-CM coding practices for a patient who has had a kidney transplant. Clinically, transplant patients are considered to have ESRD even though the transplanted kidney may be functioning well. On the other hand, ICD-10-CM requires the transplant status code Z94.0 plus a code for the current CKD stage of the transplanted kidney. All transplant patients are considered to have CKD so any of the five stages will apply, based on the GFR. As an example, the code for a patient with a GFR of 50 mL/min/1.73 m2 after transplant would be N18.3 (CKD-3) and Z94.0. The code for ESRD (N18.6) cannot be assigned because it requires chronic dialysis dependence If the transplant patient eventually became dependent on dialysis again, code N18.6 could then be assigned together with Z94.0. In summary, correct documentation of CKD stage is crucial for accurate coding, hospital reimbursement, and severity of illness classification. Clinicians should always review the calculated GFR associated with the creatinine level on clinical lab reports and remember that CKD stage can only be determined when renal function (GFR and creatinine levels) are stable, unless a recent baseline measurement is available. CKD stages are defined by either a GFR below 60 mL/min/1.73 m2 or by the presence of certain kidney damage markers for more than three months. ESRD is defined clinically as either dialysis dependence or kidney transplant status, but the ICD-10-CM definition requires dialysis dependence. Transplant patients are identified with the transplant status code (Z94.0) plus a code for the current CKD stage of the transplanted kidney. Ask Dr. Pinson Q: A patient with alcohol dependency was admitted for alcohol intoxication with confusion and disorientation. Blood alcohol level was 412 mg/dL. Subsequently he began experiencing signs and symptoms of delirium tremens (DTs) and was transferred to the ICU. In your opinion, is it appropriate to query for toxic encephalopathy due to alcohol intoxication? A: Clinicians should be aware of the coding implications of toxic encephalopathy due to alcohol. Yes, a clarification query may be submitted. Without a query, the code assignment would be: 1. Principal diagnosis code: F10.229, alcohol dependence with intoxication (present on admission [POA] indicator = yes) 2. Secondary diagnosis code: F10.231, alcohol dependence with withdrawal delirium (DTs) (POA = no, since it occurred after admission) The diagnosis-related group (DRG) is 897. If the patient's condition is clarified as toxic encephalopathy due to alcohol, then the code assignment would change to: 1. Principal diagnosis code: T51.0X4A, toxic effect of ethanol, initial encounter (POA = yes) 2. Secondary diagnosis codes: G92, toxic encephalopathy (POA = yes), followed by F10.229 (POA = yes), then F10.231 (POA = no) The resulting DRG is 917. Clinicians should also be aware that documentation of “alcoholic encephalopathy” results in assignment of code G31.2 for a chronic degenerative brain condition (Wernicke-Korsakoff) rather than acute encephalopathy due to alcohol. Q: I was disappointed by your column “Linking Severe Sepsis and Hyperlactatemia” in the June 2018 ACP Hospitalist. You seem comfortable with preserving the Sepsis-2 definition, instead of adopting the 2016 Sepsis-3 criteria that I believe should be embraced by the medical community. Hyperlactatemia is not one of the Sequential Organ Failure Assessment (SOFA) organ dysfunction parameters in the Sepsis-3 definition. A: Thank you for your concern about the Sepsis-2/Sepsis-3 controversy. The June edition of Coding Corner was written in response to a specific question from a reader working at a facility where, whether we agree with it or not, the Sepsis-2 definition is still used—a not uncommon situation at this time. The article was devoted to the diagnostic, documentation, and coding nuances of hyperlactatemia pursuant to the ICD-10-CM Official Guidelines for Coding and Reporting, the Surviving Sepsis Campaign (SSC), CMS's Hospital Inpatient Quality Reporting (IQR) system, and Sepsis-2. I believe we agree on the authoritativeness of Sepsis-3. As I wrote in the June article: “Another issue is that Sepsis-2 definitions and criteria (systemic inflammatory response syndrome [SIRS] due to infection) are no longer the authoritative clinical diagnostic standard for sepsis recognized by SSC, having been replaced by Sepsis-3, which was published in February 2016 and adopted by SSC in March 2017. Appeals of auditor denials based on Sepsis-2 criteria are unlikely to be successful, but all such cases should be reviewed for the possibility of using Sepsis-3 diagnostic criteria as the basis for appeal.” It is widely recognized that the SIRS criteria are overly sensitive, leading to overdiagnosis of sepsis in patients who are not truly “septic.” We should also acknowledge that many of our colleagues do not yet trust the sensitivity of Sepsis-3 and qSOFA without prospective outcomes research and are concerned about underrecognition of truly septic patients. Lastly, the CMS IQR measure for management of severe sepsis still follows selected SIRS diagnostic and severe sepsis criteria (not Sepsis-3/SOFA), so clinicians must utilize these Sepsis-2 criteria for initiating a severe sepsis management bundle to demonstrate quality care. This is certainly an unsettled period in the evolution of our definitions, diagnostic tools, and effective management of sepsis. I hope this discussion offers some clarity for all our readers.	4	8	0	0	0	18	0.855515	18	1,899
Like any exclusive club, heart disease has its own jargon, understandable only by other members of the club, particularly by cardiac care providers. For example, I remember lying in my CCU bed (that’s the Coronary Intensive Care Unit), trying to memorize the letters LAD (that’s the Left Anterior Descending, the large coronary artery whose blockage had caused my MI (myocardial infarction – in my case, the so-called ‘widowmaker’ heart attack). To help others needing simultaneous translation of this new lingo in your own medical records, here’s a helpful list of some of the most common acronyms/terms/abbreviations you’ll likely find around the cardiac ward. NOTE from CAROLYN: This entire patient-friendly, jargon-free glossary (all 8,000 words!) is also part of my book “A Woman’s Guide to Living with Heart Disease“ (Johns Hopkins University Press, November 2017). You can ask for it at your local library or favourite bookshop, or order it online (paperback, hardcover or e-book) at Amazon, or order it directly from my publisher, Johns Hopkins University Press (use the code HTWN to save 20% off the list price). AA – Anti-arrhythmic: Drugs used to treat patients who have irregular heart rhythms. ABI – Ankle-Brachial Index: The ratio of the blood pressure in the lower legs to the blood pressure in the arms. Compared to the arm, lower blood pressure in the leg may be an indication of blocked arteries (See PAD or Peripheral Artery Disease) Ablation – See Cardiac Ablation. ACE Inhibitor – Angiotension Converting Enzyme inhibitor: A drug that lowers blood pressure by interfering with the breakdown of a protein-like substance involved in regulating blood pressure. ACS – Acute Coronary Syndrome: An emergency condition brought on by sudden reduced blood flow to the heart. The first sign of acute coronary syndrome can be sudden stopping of your heart (cardiac arrest). AED – Automatic External Defibrillator: A portable defibrillator for use during a cardiac emergency; it can be used on patients experiencing sudden cardiac arrest by applying a brief electroshock to the heart through electrodes placed on the chest. AF or Afib – Atrial Fibrillation: An irregular and often rapid heart rate that can cause poor blood flow to the body. Afib symptoms include heart palpitations, shortness of breath, weakness or fainting. Episodes of atrial fibrillation can come and go, or you may have chronic atrial fibrillation. AFL – Atrial Flutter: A type of arrhythmia where the upper chambers of the heart (the atria) beat very fast, causing the walls of the lower chambers (the ventricles) to beat inefficiently as well. A-HCM – Apical Hypertrophic Cardiomyopathy: Also called Yamaguchi Syndrome or Yamaguchi Hypertrophy, a non-obstructive form of cardiomyopathy (a disease of the heart muscle that leads to generalized deterioration of the muscle and its pumping ability) in which a portion of the heart muscle is hypertrophied (thickened) without any obvious cause although there may be a genetic link. It was first described in individuals of Japanese descent. AI – Aortic Insufficiency: A heart valve disease in which the aortic valve does not close tightly, leading to the backward flow of blood from the aorta (the largest blood vessel) into the left ventricle (a chamber of the heart). AIVR – Accelerated Idioventricular Rhythm: Ventricular rhythm whose rate is greater than 49 beats/min but less than 100 beats/min, usually benign. (Ventricles are the two main chambers of the heart, left and right). AMI – Acute Myocardial Infarction: See MI Angiography – A technique of injecting a dye into the vascular system (through the wrist or groin artery) to outline the heart and coronary blood vessels with x-ray guidance, an angiogram can help physicians identify blockages, narrowing, or abnormalities in the coronary arteries. See also cardiac catheterization Angioplasty – An invasive but non-surgical technique for treating diseased arteries by temporarily inflating a tiny balloon inside an artery during an angiography procedure. A tiny metal stent is almost always inserted during this procedure to help keep the artery opened. Also called Percutaneous Transluminal Coronary Angioplasty (PTCA) or Percutaneous Coronary Intervention (PCI). See also: “10 Things I Didn’t Know About Angioplasty Until I Read This Book” Angina (stable) – A condition marked by distressing symptoms typically between neck and navel that come on with exertion and go away with rest, caused by an inadequate blood supply to the heart muscle typically because of narrowed coronary arteries feeding the heart muscle. Also known as Angina Pectoris. Unstable angina (UA) occurs when fatty deposits (plaques) in a blood vessel rupture or a blood clot forms, blocking or reducing flow through a narrowed artery, suddenly and severely decreasing blood flow to the heart muscle. Unstable angina is not relieved by rest; it’s dangerous and requires emergency medical attention. Antiplatelet drugs – Medications that block the formation of blood clots by preventing the clumping of platelets (examples: Plavix, Effient, Brillinta, Ticlid, etc). Heart patients, especially those with implanted stents after PCI, are often prescribed dual antiplatelet therapy (DAPT) which includes one of these prescribed meds along with daily low-dose aspirin. Aorta – The main artery of the body, carrying blood from the left side of the heart to the arteries of all limbs and organs except the lungs. Aortic Stenosis: A disease of the heart valves in which the opening of the aortic valve is narrowed. Also called AS. Aortic valve – One of four valves in the heart, this valve allows blood from the left ventricle to be pumped up (ejected) into the aorta, but prevents blood from returning to the heart once it’s in the aorta. AP – Apical Pulse: A central pulse located at the apex (pointy bottom) of the heart. Apex – the lowest (pointy) tip of the heart that points downward at the base, forming what almost looks like a rounded point. Apical Hypertrophic Cardiomyopathy (A-HCM): Also called Yamaguchi Syndrome or Yamaguchi Hypertrophy, a non-obstructive form of cardiomyopathy (a disease of the heart muscle that leads to generalized deterioration of the muscle and its pumping ability) in which a portion of the heart muscle is hypertrophied (thickened) without any obvious cause. There may be a genetic link. It was first described in people of Japanese descent. Arrhythmia – A condition in which the heart beats with an irregular or abnormal rhythm. AS – Aortic Stenosis: A disease of the heart valves in which the opening of the aortic valve is narrowed. ASA – Atrial Septal Aneurysm: An abnormally enlarged, bulging and mobile atrial septum, the membrane that separates the left and the right upper chambers of the heart (the atria); ASA is also Aspirin ASD – Atrial Septal Defect: See Septal Defect. Atrial Fibrillation – See AF or Afib Atrial Flutter – A heart rhythm problem (arrhythmia) originating from the right atrium, most often involving a large circuit that travels around the area of the tricuspid valve (between the right atrium and the right ventricle (this is called typical atrial flutter). Less commonly, atrial flutter can also result from circuits in other areas of the right or left atrium that cause the heart to beat fast (called atypical atrial flutter). Atrial Septum, the membrane that separates the left and the right upper chambers of the heart (the atria). Atrium – A chamber of the heart that receives blood from the veins and forces it into a ventricle or ventricles. Plural: atria. AV – Atrioventricular: A group of cells in the heart located between the upper two chambers (the atria) and the lower two chambers (the ventricles) that regulate the electrical current that passes through it to the ventricles. Also Atrioventricular Block: An interruption or disturbance of the electrical signal between the heart’s upper two chambers (the atria) and lower two chambers (the ventricles). Also Aortic valve: The valve that regulates blood flow from the heart into the aorta. AVNRT – Atrioventricular Nodal Re-entry Tachycardia: a heart rhythm problem that happens when there’s an electrical short circuit in the centre of the heart, one of the most common types of SVT, most often seen in people in their twenties and thirties, and more common in women than in men. BAV – Bicuspid Aortic Valve: The most common malformation of the heart valves in which the aortic valve has only two cusps instead of three. BB – Beta Blocker: A blood pressure-lowering drug that limits the activity of epinephrine, a hormone that increases blood pressure. BBB – Bundle Branch Block: – A condition in which parts of the heart’s conduction system are defective and unable to normally conduct the electrical signal, causing an irregular heart rhythm (arrhythmia). BID – Twice a Day (instructions for taking a drug) Bi-ventricular pacemaker also called Cardiac Resynchronization Therapy (CRT): an electronic pacing device that’s surgically implanted in the chest to treat the delay in heart ventricle contractions that occur in some people with heart failure BMI – Body mass index: A number that doctors use to determine if you’re overweight. BMI is calculated using a formula of weight in kilograms divided by height in meters squared (BMI =W [kg]/H [m2]). Better yet, just click here to figure out your own BMI. BNP blood test – BNP (B-type Natriuretic Peptide) is a substance secreted from the ventricles or lower chambers of the heart in response to changes in pressure that happen when heart failure develops and/or worsens. The level of BNP in the blood increases when heart failure symptoms worsen, and decreases when the heart failure condition is stable. BP – Blood Pressure: The force or pressure exerted by the heart in pumping blood; the pressure of blood in the arteries. See also hypertension. BPM – Beats per minute Broken Heart Syndrome – See Takotsubo Cardiomyopathy BrS – Brugada Syndrome: Brugada syndrome is a genetic heart disease that is characterized by distinctively abnormal electrocardiogram (EKG/ECG) findings and an increased risk of sudden cardiac arrest. Bypass surgery – see CABG CAA – Coronary artery anomaly: A congenital defect in one or more of the coronary arteries of the heart. CABG – Coronary Artery Bypass Graft: A surgical procedure that reroutes blood flow around a diseased or blocked blood vessel that supplies blood to the heart by grafting either a piece of vein harvested from the leg or the artery from under the breastbone. CA – Coronary Artery: The arteries arising from the aorta that arch down over the top of the heart and divide into branches. They provide blood to the heart muscle. CAD – Coronary Artery Disease: A narrowing of the arteries that supply blood to the heart. The condition results from a plaque rupture/blood clot or spasm and greatly increases the risk of a heart attack. Cardiac Ablation – A procedure performed by an Electrophysiologist (EP) – a cardiologist with specialized training in treating heart rhythm problems – that typically uses catheters — long, flexible tubes inserted through a vein in the groin and threaded to the heart — to correct structural problems in the heart that cause an arrhythmia. Cardiac ablation works by scarring or destroying the tissue in your heart that triggers an abnormal heart rhythm. Cardiac Arrest – Also known as Sudden Cardiac Arrest: The stopping of the heartbeat, usually because of interference with the electrical signal that regulates each heartbeat (often associated with coronary heart disease). Can lead to Sudden Cardiac Death. Cardiac Catheterization – An invasive procedure in which a catheter is inserted through a blood vessel in the wrist/arm or groin with x-ray guidance. This procedure can help provide information about blood supply through the coronary arteries, blood pressure, blood flow throughout the chambers of the heart, collection of blood samples, and x-rays of the heart’s ventricles or arteries. It’s typically performed in the cath lab during angiography. Cardiac Perfusion Scan – See MIBI Cardiac Resynchronization Therapy (CRT) also called bi-ventricular pacemaker: an electronic pacing device that’s surgically implanted in the chest to treat the delay in heart ventricle contractions that occur in some people with heart failure. Cardiac Tamponade – Pressure on the heart that occurs when blood or fluid builds up in the space between the heart muscle (myocardium) and the outer covering sac of the heart (pericardium). Also called Tamponade. Cardiomyopathy – a chronic disease of the heart muscle (myocardium), in which the muscle is abnormally enlarged, thickened, and/or stiffened. Cardioversion – A medical procedure in which an abnormally fast heart rate (tachycardia) or cardiac arrhythmia like atrial fibrillation is converted to a normal rhythm using electricity or drugs. Synchronized electrical cardioversion uses a therapeutic dose of electric current to the heart at a specific moment in the cardiac cycle. Chemical cardioversion uses medications to convert to normal rhythm. Cath lab – the room in the hospital/medical clinic where cardiac catheterization procedures take place (for example, when a stent is implanted into a blocked coronary artery). Catheter – a cardiac catheter is a very long thin tube inserted into an artery or vein in your groin (mostly in the U.S.), wrist or arm (everywhere else) – and threaded through blood vessels up to the heart during angiography CCB – Calcium Channel Blocker: A drug that lowers blood pressure by regulating calcium-related electrical activity in the heart. CDS – Cardiac Depression Scale: A scale that can help assess the effects of depression occurring as a result of a heart disease diagnosis. CHF – Heart Failure (also called Congestive Heart Failure): A condition in which the heart cannot pump all the blood returning to it, leading to a backup of blood in the vessels and an accumulation of fluid in the body’s tissues, including the lungs. Cholesterol: a waxy substance that’s found in the fats (lipids) in your blood. The body needs cholesterol to continue building healthy cells, but it’s believed that having high cholesterol may increase the risk of developing heart disease. See also: LDL, HDL CM – Cardiomyopathy: A disease of the heart muscle that leads to generalized deterioration of the muscle and its pumping ability. CO – Cardiac Output: The amount of blood the heart pumps through the circulatory system in one minute. Collateral arteries – These extra coronary blood vessels are sometimes able to bypass a blockage in an artery in order to supply enough oxygenated blood to enable the heart muscle to survive when in danger of being damaged because of blockage(s). Collateral arteries – Blood vessels that provide an alternative arterial supply of blood to an area of the heart that’s in danger of being deprived of oxygenated blood because of one or more blocked arteries. Congenital heart defect – one of about 35 different types of heart conditions that happen when the heart or the blood vessels near the heart don’t develop normally before a baby is born (in about 1% of live births). Because of medical advances that treat babies born with heart defects, there are now for the first time more adults with congenital heart disease than children. Congestive heart failure (CHF) – a chronic progressive condition that affects the pumping power of your heart muscle. Often referred to simply as heart failure, CHF specifically refers to the stage in which fluid builds up around the heart and causes it to pump inefficiently. COPD – Chronic Obstructive Pulmonary Disease: A lung disease defined by persistently poor airflow as a result of breakdown of lung tissue (known as emphysema) and dysfunction of the small airways.Often associated with smoking, it typically worsens over time. Coronary Microvascular Disease – A heart condition that causes impaired blood flow to the heart muscle through the small vessels of the heart. Also called Microvascular Disease or Small Vessel Disease. Coronary Reactivity Test – An angiography procedure specifically designed to examine the blood vessels in the heart and how they respond to different medications. Physicians use these images to distinguish different types of blood vessel reactivity dysfunction (such as Coronary Microvascular Disease). Costochondritis– the cause of severe chest pain, but NOT heart-related; it’s an inflammation of the cartilage that connects a rib to the breastbone. Coumadin – A drug taken to prevent the blood from clotting and to treat blood clots. Coumadin is believed to reduce the risk of blood clots causing strokes or heart attacks. See also Warfarin. Cox Maze procedure – A complex “cut-and-sew” surgical procedure done to treat atrial fibrillation through a complicated set of incisions made in a maze-like pattern on the left and right atria (the upper chambers of the heart) to permanently interrupt the abnormal electrical signals that are causing the irregular heartbeats of Afib. See also: Mini-Maze. CP – Chest Pain (may also be felt as squeezing, pressure, fullness, pressure, heaviness, burning or tightness in the chest). CPR – Cardiopulmonary Resuscitation: An emergency procedure in which the heart and lungs are made to work by manually compressing the chest overlying the heart and forcing air into the lungs, used to maintain circulation when the heart stops pumping during Cardiac Arrest. Current guidelines suggest hands-only CPR. See also AED. CQ10 – Co-enzyme Q10: A dietary supplement sometimes recommended for heart patients taking statin drugs. CRP – C-reactive protein: A byproduct of inflammation, produce by the liver, found in the blood in some cases of acute inflammation. CRT – Cardiac Resynchronization Therapy also called bi-ventricular pacemaker: an electronic pacing device that’s surgically implanted in the chest to treat the delay in heart ventricle contractions that occur in some people with heart failure. CT – Computed tomography (CT or CAT scan): An x-ray technique that uses a computer to create cross-sectional images of the body. CTA – Computerized Tomographic Angiogram: An imaging test to look at the arteries that supply the heart muscle with blood. Unlike a traditional coronary angiogram, CT angiograms don’t use a catheter threaded through your blood vessels to your heart but instead rely on a powerful X-ray machine to produce images of your heart and heart vessels. CV – Coronary Vein: One of the veins of the heart that drain blood from the heart’s muscular tissue and empty into the right atrium. CV – Cardiovascular: Pertaining to the heart and blood vessels that make up the circulatory system. DBP – Diastolic blood pressure: The lowest blood pressure measured in the arteries. It occurs when the heart muscle is relaxed between beats. DCM – Dilated Cardiomyopathy: A disease of the heart muscle, primarily affecting the heart’s main pumping chamber (left ventricle). The left ventricle becomes enlarged (dilated) and can’t pump blood to your body with as much force as a healthy heart can. DDI – Drug-drug interaction: A situation in which a medication affects the activity of another medication when both are administered together. DIL – Diltiazem: A calcium channel blocker drug that acts as a vasodilator; used in the treatment of angina pectoris, hypertension, and supraventricular tachycardia. Diuretic – A class of drugs used to lower blood pressure. Also known as “water pills”. Dobutamine stress echocardiography: This is a form of a stress echocardiogram diagnostic test. But instead of exercising on a treadmill or exercise bike to stress the heart, the stress is obtained by giving a drug that stimulates the heart and makes it “think” it’s exercising. The test is used to evaluate your heart and valve function if you are unable to exercise. It is also used to determine how well your heart tolerates activity, and your likelihood of having coronary artery disease (blocked arteries), and it can evaluate the effectiveness of your cardiac treatment plan. See also TTE and Stress Echocardiogram. Door-to-balloon time: The time between the arrival at a hospital of a patient with an acute heart attack and the opening of that patient’s blocked coronary artery via balloon angioplasty (and usually a stent). The recommended time is 90 minutes or less for best outcomes. Dressler’s syndrome: Happens to a small number of people three to four weeks after a heart attack. The heart muscle that died during the attack sets the immune system in motion, calling on lymphocytes, one of the white blood cells, to infiltrate the coverings of the heart (pericardium) and the lungs (pleura). It also starts generating antibodies, which attack those two coverings. Chest pain (CP) is the predominant symptom; treated with anti-inflammatory drugs. Dual Antiplatelet Therapy: Medications that block the formation of blood clots by preventing the clumping of platelets (examples Plavix, Effient, Brillinta, Ticlid, etc.) are often prescribed along with aspirin as part of what’s known as dual antiplatelet therapy, especially to patients who have undergone PCI and stent implantation. DVT – Deep Vein Thrombosis: A blood clot in a deep vein in the calf. EAT – Ectopic Atrial Tachycardia: A type of atrial arrhythmia characterized by fast and regular heart rates ranging from 140–220 bpm ECG / EKG – Electrocardiogram: A test in which several electronic sensors are placed on the body to monitor electrical activity associated with the heartbeat. Echocardiogram: A test of the action and functioning of the heart using ultrasound waves to produce a visual display, used for the diagnosis or monitoring of heart disease; a stress echocardiogram adds an exercise component to make the heart beat faster before the echo is recorded. See also: NWMA Ectopic beats: small changes in an otherwise normal heartbeat that lead to extra or skipped heartbeats, often occurring without a clear cause, most often harmless. EECP: see Enhanced External Counterpulsation EF: Ejection Fraction: A measurement of blood that is pumped out of a filled ventricle. The normal rate is 50-60%. Ehlers-Danlos syndromes: a group of 13 types of connective tissue disorders that can be inherited, affecting mostly joints and skin (can be linked to the heart condition called mitral valve prolapse.) EKG/ECG – Electrocardiogram: A test in which several electronic sensors are placed on the body to monitor electrical activity associated with the heartbeat. Endothelium: A single-cell layer of flat endothelial cells lining the closed internal spaces of the body such as the inside of blood vessels. Endothelial dysfunction affects the ability of these cells to help dilate blood vessels, control inflammation or prevent blood clots. The endothelium is associated with most forms of cardiovascular disease, such as hypertension, coronary artery disease, chronic heart failure, peripheral vascular disease, diabetes, chronic kidney failure, and severe viral infections. Enhanced External Counterpulsation – EECP is an FDA-approved non-invasive, non-drug treatment for angina. It works by promoting the development of collateral coronary arteries. The therapy is widely used in prominent heart clinics such as the Cleveland Clinic, Mayo Clinic and Johns Hopkins – especially for patients who are not good candidates for invasive procedures such as bypass surgery, angioplasty or stenting. EP – Electrophysiologist: A cardiologist who has additional training in diagnosing/treating heart rhythm disorders. EPS – Electrophysiology Study: A test that uses cardiac catheterization to study patients who have arrhythmias (abnormal hear rhythm). An electrical current stimulates the heart in an effort to provoke an arrhythmia, which is immediately treated with medications. EPS is used primarily to identify the origin of the arrhythmia and to test the effectiveness of medications used to treat abnormal heart rhythms. EVH – Endoscopic Vessel Harvesting: To create the bypass graft during CABG open heart surgery, a surgeon will remove or “harvest” healthy blood vessels from another part of the body, often from the patient’s leg or arm. This vessel becomes a graft, with one end attaching to a blood source above and the other end below the blocked area. See CABG. Exercise stress test – An exercise test (walking/running on a treadmill or pedalling a stationary bike) to make your heart work harder and beat faster. An EKG is recorded while you exercise to monitor any abnormal changes in your heart under stress, with or without the aid of drugs to enhance this assessment. See also: MIBI, Echocardiogram, Nuclear Stress Test. Familial hypercholesterolemia (FH) – A genetic predisposition to dangerously high cholesterol levels. FH is an inherited disorder that can lead to aggressive and premature cardiovascular disease, including problems like heart attacks, strokes, or narrowing of the heart valves. Femoral Artery: a major artery in your groin/upper thigh area, through which a thin catheter is inserted, eventually making its way into the heart during angioplasty to implant a stent; currently the most widely used angioplasty approach in the United States, but many other countries now prefer the Radial Artery access in the wrist. FFR – Fractional Flow Reserve: A test used during coronary catheterization (angiogram) to measure pressure differences across a coronary artery stenosis (narrowing or blockage) defined as as the pressure behind a blockage relative to the pressure before the blockage. FH – see Familial hypercholesteremia (above) GTN – Glyceryl trinitrate: See Nitroglycerin or NTG HC – High Cholesterol: When fatty deposits build up in your coronary arteries. HCM – Hypertrophic Cardiomyopathy: A heart condition that damages the muscle wall of the lower chambers of the heart and causes them to thicken abnormally. HCM is perhaps best known as a leading cause of sudden cardiac death in young athletes. (Also HOCM: Hypertrophic Obstructive Cardiomyopathy) HCTZ – Hydrochlorothiazide: A drug used to lower blood pressure; it acts by inhibiting the kidneys’ ability to retain water. Used to be called “water pills”. HDL – High Density Lipoprotein: A component of cholesterol, HDL helps protect against heart disease by promoting cholesterol breakdown and removal from the blood; hence, its nickname “good cholesterol.” Heart Attack – The damage or death of an area of the heart muscle (myocardium) resulting from a blocked blood supply to the area. The affected tissue dies, injuring the heart. Also Myocardial Infarction, MI) Heart Failure – a chronic progressive condition that affects the pumping power of your heart muscle. Sometimes called Congestive Heart Failure (CHF). Holiday Heart – See Paroxysmal Atrial Fibrillation Holter Monitor – A portable monitoring device that patients wear for recording heartbeats over a period of 24 hours or more. HTN – Hypertension: High blood pressure, the force of blood pushing against the walls of arteries as it flows through them. Hypertension (HTN): High blood pressure, the force of blood pushing against the walls of arteries as it flows through them. Also BP Hypokinesia – Decreased heart wall motion during each heartbeat, associated with cardiomyopathy, heart failure, or heart attack. Hypokinesia can involve small areas of the heart (segmental) or entire sections of heart muscle (global). Also called hypokinesis. ICD – Implantable Cardioverter Defibrillator: A surgically implanted electronic device to treat life-threatening heartbeat irregularities. IHD – Ischemic Heart Disease: heart problems caused by narrowing of the coronary arteries, causing a decreased blood supply to the heart muscle. Also called coronary artery disease and coronary heart disease. Inferior Vena Cava – a large vein carrying de-oxygenated blood from the lower body into the right atrium of the heart. See also Superior Vena Cava INR – International Normalized Ratio: A laboratory test measure of blood coagulation, often used as a standard for monitoring the effects of the anti-coagulant drug, warfarin (coumadin). IST – Inappropriate sinus tachycardia: A heart condition seen most often in young women, in which a person’s resting heart rate is abnormally high (greater than 100 bpm), their heart rate increases rapidly with minimal exertion, and this rapid heart rate is accompanied by symptoms of palpitations, fatigue, and/or exercise intolerance. Interventional cardiologist – A cardiologist who is trained to perform invasive heart procedures like angiography, angioplasty, percutaneous coronary intervention (PCI), implanting stents, etc. IVS – Interventricular Septum: The stout wall that separates the lower chambers (the ventricles) of the heart from one another. IVUS – Intravascular Ultrasound: A form of echocardiography performed during cardiac catheterization in which a transducer (a device that can act as a transmitter (sender) and receiver of ultrasound information) is threaded into the heart blood vessels via a catheter; it’s used to provide detailed information about the blockage inside the blood vessels. LAD – Left Anterior Descending coronary artery: One of the heart’s coronary artery branches from the left main coronary artery which supplies blood to the left ventricle. LAFB – Left Anterior Fascicular Block: A cardiac condition,distinguished from Left Bundle Branch Block because only the anterior half of the left bundle branch is defective and more common than left posterior fascicular block. LAHB – Left Anterior Hemiblock: The Left Bundle Branch divides into two major branches – the anterior and the posterior fascicles. Occasionally, a block can occur in one of these fascicles. LBBB – Left Bundle Branch Block: A heart arrhythmia in which activation of the left ventricle is delayed which causes the left ventricle to contract later than the right ventricle. See also Right Bundle Branch Block and LAFB LDL – Low Density Lipoprotein: The body’s primary cholesterol-carrying molecule. High blood levels of LDL may increase your risk of heart disease by promoting cholesterol attachment and accumulation in blood vessels; often called “bad cholesterol.” Left Circumflex Artery – The artery carries oxygenated blood from the heart to the body; it’s a branch of the Left Main Coronary Artery after the latter runs its course in between the aorta and the Main Pulmonary Artery. Left Main Coronary Artery – The artery that branches from the aorta to supply oxygenated blood to the heart via the Left Anterior Descending Artery (LAD) and the Left Circumflex Artery. Lipids – fat-like substances found in your blood and body tissues; a lipid panel is a blood test that measures the level of specific lipids in blood to help assess your risk of cardiovascular disease, measuring four types of lipids: total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Lipoprotein-a or Lp(a) – molecules made of proteins and fat, carrying cholesterol and similar substances through the blood. A high level of Lp(a) is considered a risk factor for heart disease; detectable via a blood test. Long QT syndrome (LQTS): A heart rhythm disorder that can potentially cause fast, chaotic heartbeats that may trigger a sudden fainting spell or seizure. In some cases, the heart may beat erratically for so long that it can cause sudden death. LOS – length of stay in hospital (also PLOS: postoperative length of stay) LQTS – see Long QT syndrome LV – Left Ventricle – One of four chambers (two atria and two ventricles) in the human heart, it receives oxygenated blood from the left atrium via the mitral valve, and pumps it into the aorta via the aortic valve. LVAD – Left ventricular assist device: A mechanical device that can be placed outside the body or implanted inside the body. An LVAD does not replace the heart – it “assists” or “helps” it pump oxygen-rich blood from the left ventricle to the rest of the body, usually as a bridge to heart transplant. LVH – Left Ventricular Hypertrophy: A thickening of the myocardium (muscle) of the Left Ventricle (LV) of the heart.. Lumen – The hollow area within a tube, such as a blood vessel. Main Pulmonary Artery – Carries oxygen-depleted blood from the heart to the lungs. MI – Myocardial Infarction or heart attack. The damage or death of an area of the heart muscle (myocardium) resulting from a blocked blood supply to the area. The affected tissue dies, injuring the heart. (Also: Mitral Insufficiency or Mitral Incompetence- see Mitral Regurgitation) MIBI – Nuclear Stress Test/Cardiac Perfusion Scan/Sestamibi: tests that are used to assess the blood flow to the heart muscle (myocardium) when it is stressed by exercise or medication, and to find out what areas of the myocardium have decreased blood flow due to coronary artery disease. This is done by injecting a tiny amount of radionuclide like thallium or technetium (chemicals which release a type of radioactivity called gamma rays) into a vein in the arm or hand. Microvascular disease – a heart condition that causes impaired blood flow to the heart muscle through the small blood vessels of the heart. Symptoms mimic those of a heart attack. Also called Coronary Microvascular Disease or Small Vessel Disease. I live with this diagnosis and have written more about it here, here and here. Mini-Maze – a surgical procedure to treat atrial fibrillation, less invasive than what’s called the Cox Maze III procedure (a “cut-and-sew” procedure) and performed on a beating heart without opening the chest. Mitral Valve: One of four valves in the heart, the structure that controls blood flow between the heart’s left atrium (upper chamber) and left ventricle (lower chamber). The mitral valve has two flaps (cusps). See also MV and/or Valves. Mitral valve prolapse: a condition in which the two valve flaps of the mitral valve don’t close smoothly or evenly, but instead bulge (prolapse) upward into the left atrium; also known as click-murmur syndrome, Barlow’s syndrome or floppy valve syndrome. MR – Mitral regurgitation: (also mitral insufficiency or mitral incompetence) a heart condition in which the mitral valve does not close properly when the heart pumps out blood. It’s the abnormal leaking of blood from the left ventricle, through the mitral valve and into the left atrium when the left ventricle contracts. MRI – Magnetic Resonance Imaging: A technique that produces images of the heart and other body structures by measuring the response of certain elements (such as hydrogen) in the body to a magnetic field. An MRI can produce detailed pictures of the heart and its various structures without the need to inject a dye. MS – Mitral Stenosis: A narrowing of the mitral valve, which controls blood flow from the heart’s upper left chamber (the left atrium) to its lower left chamber (the left ventricle). May result from an inherited (congenital) problem or from rheumatic fever. MUGA – Multiple-Gated Acquisition Scanning: A non-invasive nuclear test that uses a radioactive isotope called technetium to evaluate the functioning of the heart’s ventricles. Murmur – Noises superimposed on normal heart sounds. They are caused by congenital defects or damaged heart valves that do not close properly and allow blood to leak back into the originating chamber. MV – Mitral Valve: The structure that controls blood flow between the heart’s left atrium (upper chamber) and left ventricle (lower chamber). MVD – Microvascular Disease: A condition in which the small arteries in the heart become narrowed. Small vessel disease causes signs and symptoms of heart disease, such as chest pain (angina). Small vessel disease is sometimes called coronary microvascular disease or small vessel heart disease. Also called Small Vessel Disease or Coronary Microvascular Disease MVP – Mitral Valve Prolapse: A condition that occurs when the leaflets of the mitral valve between the left atrium (upper chamber) and left ventricle (lower chamber) bulge into the atrium and permit backflow of blood into the atrium. The condition is often associated with progressive mitral regurgitation. Also MVPS: Mitral Valve Prolapse Syndrome MVR – Mitral Valve Regurgitation: Failure of the mitral valve to close properly, causing blood to flow back into the heart’s upper left chamber (the left atrium) instead of moving forward into the lower left chamber (the left ventricle). or Mitral Valve Repair (aka MR) Myocardial Infarction (MI, heart attack) – The damage or death of an area of the heart muscle (myocardium) resulting from a blocked blood supply to the area. The affected tissue dies, injuring the heart. Myocardium – The muscular tissue of the heart. Myxoma – The most common form of non-cancerous tumour in the heart. About 75% of the time, it’s an atrial myxoma is a non-cancerous tumour in the upper left or right side of the heart, most often growing on the wall that separates the two sides of the heart (this wall is called the atrial septum). An untreated myxoma can lead to an embolism (a clot that breaks off and travels in the bloodstream). New Wall-Motion Abnormalities – Results seen on an echocardiogram test report (see NWMA, below). Nitroglycerin – A medicine that helps relax and dilate arteries; often used to treat cardiac chest pain (angina). Also called NTG or GTN. NSR – Normal Sinus Rhythm: The characteristic rhythm of the healthy human heart. NSR is considered to be present if the heart rate is in the normal range, the P waves are normal on the EKG/ECG, and the rate does not vary significantly. NSTEMI – Non-ST-segment-elevation myocardial infarction: The milder form of the two main types of heart attack. An NSTEMI heart attack does not produce an ST-segment elevation seen on an electrocardiogram test (EKG). See also STEMI. NTG – See Nitroglycerin Nuclear Stress Test – A diagnostic test that usually involves two exercise stress tests, one while you’re exercising on a treadmill/stationary bike or with medication that stresses your heart, and another set while you’re at rest. A nuclear stress test is used to gather information about how well your heart works during physical activity and at rest. See also: Exercise stress test, Nuclear perfusion test, MIBI. NWMA – Seen on an echocardiogram test report, meaning: “New Wall-Motion Abnormalities”. A study published in the journal Circulation reported: “If an echocardiogram shows no clear diagnosis of cardiovascular disease but does show a wall-motion abnormality, this can identify individuals who are at increased risk and probably have underlying coronary artery disease.” Open heart surgery – Any surgery in which the chest is opened and surgery is done on the heart muscle, valves, coronary arteries, or other parts of the heart. See also CABG. Pacemaker – A surgically implanted electronic device that helps regulate the heartbeat. PAD – Peripheral Artery Disease: A common circulatory problem in which narrowed arteries reduce blood flow to the limbs, usually to the legs. Symptoms include leg pain when walking (called intermittent claudication). PAF – Paroxysmal Atrial Fibrillation: Atrial fibrillation that lasts from a few seconds to days, then stops on its own. See also Atrial Fibrillation. Palpitations – A noticeably rapid, strong, or irregular heartbeat due to agitation, exertion or illness. Paroxysmal Atrial Fibrillation – An unusual heart arrhythmia of unknown origin, at one time believed to be associated with an unusual sensitivity to alcohol consumption. Patent ductus arteriosus: see PDA PCI – Percutaneous Coronary Intervention (or angiography): Any of the procedures usually performed in the cardiac catheterization laboratory (also called the cath lab). Angioplasty is an example of a percutaneous coronary intervention. Also called a transcatheter intervention or Percutaneous Transluminal Coronary Angioplasty (PTCA) PDA – patent ductus arteriosus: A persistent opening between two major blood vessels leading from the heart. The opening is called ductus arteriosus and is a normal part of a baby’s circulatory system before birth that usually closes shortly after birth. But when it remains open, it’s called a patent ductus arteriosus. If it’s small, it may never need treatment, but a large PDA left untreated can allow poorly oxygenated blood to flow in the wrong direction, weakening the heart muscle and causing heart failure or other complications. Pericarditis – inflammation of the pericardium Pericardium: two thin layers of a sac-like tissue that surround the heart, hold it in place and help it work. PET – Positron Emission Tomography: A non-invasive scanning technique that uses small amounts of radioactive positrons (positively charged particles) to visualize body function and metabolism. In cardiology, PET scans are used to evaluate heart muscle function in patients with coronary artery disease or cardiomyopathy. PFO – Patent Forman Ovale: An opening between the left and right atria (the upper chambers) of the heart. Everyone has a PFO before birth, but in 1 out of every 3 or 4 people, the opening does not close naturally as it should after birth. Plaque – A deposit of fatty (and other) substances in the inner lining of the artery wall; it is characteristic of atherosclerosis. PLOS – postoperative length of stay in hospital (see also LOS: length of stay) POTS – Postural Orthostatic Tachycardia Syndrome: A disorder that causes an increased heart rate when a person stands upright. PPCM – Post-partum cardiomyopathy: A form of cardiomyopathy that causes heart failure toward the end of pregnancy or in the months after delivery, in the absence of any other cause of heart failure. Preeclampsia – a late-pregnancy complication identified by spikes in blood pressure, protein in the urine, possible vision problems. Women who experience pregnancy complications like preeclampsia are at significantly higher risk for heart disease. Prinzmetal’s Variant Angina – Chest pain caused by a spasm in a coronary artery that supplies blood to the heart muscle. PRN – “As needed” – from the Latin “pro re nata” meaning “as the circumstance arises” (used when medications are being prescribed to patients, not at specified times, but only when you need them) PSVT – Paroxysmal Supraventricular Tachycardia: – An occasional rapid heart rate (150-250 beats per minute) that is caused by events triggered in areas above the heart’s lower chambers (the ventricles). “Paroxysmal” means from time to time. See also supraventricular tachycardia (SVT). PTCA – Percutaneous Transluminal Coronary Angioplasty: See Angioplasty Pulmonary Valve: One of the four valves in the heart, located between the pulmonary artery and the right ventricle of the heart, moves blood toward the lungs and keeps it from sloshing back into the heart. PV – Pulmonary Vein: A vein carrying oxygenated blood from the lungs to the left atrium of the heart. PVC – Premature Ventricular Contraction: An early or extra heartbeat that happens when the heart’s lower chambers (the ventricles) contract too soon, out of sequence with the normal heartbeat. In the absence of any underlying heart disease, PVCs do not generally indicate a problem with electrical stability, and are usually benign. QD – Every day (instructions for taking a drug) QID – Four times a day (instructions for taking a drug) RA – Right Atrium: The right upper chamber of the heart. The right atrium receives de-oxygenated blood from the body through the vena cava and pumps it into the right ventricle which then sends it to the lungs to be oxygenated. Radial Artery: the artery in the wrist where a thin catheter is inserted through the body’s network of arteries in the arm and eventually into the heart during a procedure to implant a stent. Doctors may also call this transradial access, the transradial approach, or transradial angioplasty. Because it’s associated with fewer complications, this is increasingly considered the default access approach in most countries, except in the U.S. where the traditional Femoral Artery (groin) approach is still the most popular access. RBBB – Right Bundle Branch Block: A delay or obstruction along the pathway that electrical impulses travel to make your heart beat. The delay or blockage occurs on the pathway that sends electrical impulses to the right side of your heart. See also Left Bundle Branch Block. RCA – Right Coronary Artery: An artery that supplies blood to the right side of the heart. Restenosis – The re-closing or re-narrowing of an artery after an interventional procedure such as angioplasty or stent placement. Sometimes called “stent failure”. RHD – Rheumatic Heart Disease: Permanent damage to the valves of the heart caused especially by repeated attacks of rheumatic fever. RM – Right Main coronary artery: A blood vessel that supplies oxygenated blood to the walls of the heart’s ventricles and the right atrium. RV – Right Ventricle: The lower right chamber of the heart that receives de-oxygenated blood from the right atrium and pumps it under low pressure into the lungs via the pulmonary artery. SA – Sinus node: The “natural” pacemaker of the heart. The node is a group of specialized cells in the top of the right atrium which produces the electrical impulses that travel down to eventually reach the ventricular muscle, causing the heart to contract. SB – Sinus Bradycardia: Abnormally slow heartbeat. SBP – Systolic Blood Pressure: The highest blood pressure measured in the arteries. It occurs when the heart contracts with each heartbeat. Example: the first number in 120/80. SCAD – Spontaneous Coronary Artery Dissection: A rare emergency condition that occurs when a tear forms in one of the blood vessels in the heart, causing a heart attack, abnormalities in heart rhythm and/or sudden death. SCAD tends to strike young healthy women with few if any cardiac risk factors. SCD – Sudden Cardiac Death: Death as a result of Cardiac Arrest SD – Septal defect: A hole in the wall of the heart separating the atria (two upper chambers of the heart) or in the wall of the heart separating the ventricles (two lower chambers). Sestamibi stress test – See MIBI. Short QT intervals (SQT): An abnormal heart rhythm where the heart muscle takes a shorter time to recharge between beats. It can cause a variety of complications from fainting and dizziness to sudden cardiac arrest. Sick Sinus Syndrome (also known as sinus node dysfunction) is caused by an electrical problem in the heart; a group of related heart conditions that can affect how the heart beats, most commonly in older adults, although it can be diagnosed in people of any age. “Sick sinus” refers to the sinoatrial node (see below). In people with sick sinus syndrome, the SA node does not function normally. Sinoatrial node (SA): also commonly called the sinus node; it’s a small bundle of neurons situated in the upper part of the wall of the right atrium (the right upper chamber of the heart). The heart’s electrical impulses are generated there. It’s the normal natural pacemaker of the heart and is responsible for the initiation of each heartbeat. SOB – Shortness of breath Spontaneous Coronary Artery Dissection (SCAD) – A rare emergency condition that occurs when a tear forms in one of the blood vessels in the heart, causing a heart attack, abnormalities in heart rhythm and/or sudden death. SCAD tends to strike young healthy women with few if any cardiac risk factors. Small Vessel Disease – See Microvascular Disease Spasm – see Vasospasm. SQT – see Short QT intervals SSS – Sick Sinus Syndrome: The failure of the sinus node to regulate the heart’s rhythm. ST – Sinus Tachycardia: A heart rhythm with elevated rate of impulses originating from the sinoatrial node, defined as greater than 100 beats per minute (bpm) in an average adult. The normal heart rate in the average adult ranges from 60–100 bpm. Also called sinus tach or sinus tachy. Statins – Any of a class of drugs that lower the levels of low-density lipoproteins (LDL) – the ‘bad’ cholesterol in the blood – by inhibiting the activity of an enzyme involved in the production of cholesterol in the liver. Examples of brand name statins: Lipitor, Crestor, Zocor, Mevacor, Levachol, Lescol, etc. Also available as a cheaper generic form of the drug. STEMI – ST-elevation heart attack (myocardial infarction). The more severe form of the two main types of heart attack. A STEMI produces a characteristic elevation in the ST segment on an electrocardiogram (EKG). The elevated ST segment is how this type of heart attack got its name. See also NSTEMI. Stenosis – a narrowing of a passage in the body. See Aortic Stenosis Stent – An implantable device made of expandable, metal mesh (looks a bit like a tiny chicken wire tube) that is placed (by using a balloon catheter) at the site of a narrowing coronary artery during an angioplasty procedure. The stent is then expanded when the balloon fills, the balloon is removed, and the stent is left in place to help keep the artery open. TRIVIA ALERT: the coronary stent was named after Charles Stent (1807-1885), an English dentist who invented a compound to produce dentures and other things like skin grafts and hollow tubes (essentially what a metal coronary stent is). His real claim to fame occurred when he suggested using his material to coat underwater trans-Atlantic cable, which had broken several times as a result of corrosion by seawater. You’re welcome. Stint – a common spelling mistake when what you really mean is the word “stent” (see above). Stress test – A diagnostic test meant to assess the effects of exercise on the heart’s ability to function. See also: Nuclear Stress Test, MIBI, Exercise Stress Test, Stress Echocardiogram, Stress Echocardiography – A standard echocardiogram test that’s performed while the person exercises on a treadmill or stationary bicycle. This test can be used to visualize the motion of the heart’s walls and pumping action when the heart is stressed, possibly revealing a lack of blood flow that isn’t always apparent on other heart tests. The echocardiogram is performed just before and just after the exercise part of the procedure. See also TTE. Sudden Cardiac Arrest – The stopping of the heartbeat, usually because of interference with the electrical signal (often associated with coronary heart disease). Can lead to Sudden Cardiac Death. Superior Vena Cava – large vein carrying blood from the head, arms, and upper body to the right atrium of the heart. Sometimes called precava. See also Inferior Vena Cava SVT – Supraventricular Tachycardia: An occasional rapid heart rate (150-250 beats per minute) that is caused by events triggered in areas above the heart’s lower chambers (the ventricles); see also paroxysmal supraventricular tachycardia (PSVT). Also: Sustained Ventricular Tachycardia Takotsubo Cardiomyopathy – A heart condition that can mimic a heart attack. Sometimes called Broken Heart Syndrome, it is not a heart attack, but it feels just like one, with common symptoms like severe chest pain and shortness of breath. It sometimes follows a severe emotional stress. Over 90% of reported cases are in women ages 58 to 75. Also referred to as Broken Heart Syndrome, stress cardiomyopathy, stress-induced cardiomyopathy or apical ballooning syndrome. Tamponade – see Cardiac Tamponade TAVR – Transcatheter aortic valve replacement: A minimally invasive procedure to repair a damaged or diseased aortic valve. A catheter is inserted into an artery in the groin and threaded to the heart. A balloon at the end of the catheter, with a replacement valve folded around it, delivers the new valve to take the place of the old. Also called TAVI (Transcatheter aortic valve implantation). Tetralogy of Fallot – A rare condition caused by a combination of four heart defects that are present at birth, affecting the structure of the heart and causing oxygen-poor blood to flow out of the heart and into the rest of the body. Infants and children with Tetralogy of Fallot usually have blue-tinged skin because their blood doesn’t carry enough oxygen. Often diagnosed in infancy, but sometimes not until later in life depending on severity. Tg – Triglycerides: The most common fatty substance found in the blood; normally stored as an energy source in fat tissue. High triglyceride levels may thicken the blood and make a person more susceptible to clot formation. High triglyceride levels tend to accompany high cholesterol levels and other risk factors for heart disease, such as obesity. Thallium Stress Test – See Nuclear Stress Test TIA – Transient Ischemic Attack: A stroke-like event that lasts only for a short time and is caused by a temporarily blocked blood vessel. TID – Three times a day (instructions for taking a drug) TEE – Transesophageal echocardiogram: This test involves an ultrasound transducer inserted down the throat into the esophagus in order to take clear images of the heart structures without the interference of the lungs and chest. Treadmill Stress Test – See Exercise Stress Test. Tricuspid Valve – One of four valves in the heart, a valve with three little flaps that keeps blood in the right ventricle from flowing back into the right atrium. See also Valves troponin – a type of cardiac enzyme found in heart muscle, and released into the blood when there is damage to the heart (for example, during a heart attack). A positive blood test that shows elevated troponin is the preferred test for a suspected heart attack because it is more specific for heart injury than other blood tests, especially the newer high sensitivity troponin tests (hs-cTnT). TTE – Transthoracic Echocardiogram: This is the standard echocardiogram, a painless test similar to X-ray, but without the radiation, using a hand-held device called a transducer placed on the chest to transmit high frequency sound waves (ultrasound). These sound waves bounce off the heart structures, producing images and sounds that can be used by the doctor to detect heart damage and disease. TV – Tricuspid Valve: One of four one-way valves in the heart, a structure that controls blood flow from the heart’s upper right chamber (the right atrium) into the lower right chamber (the right ventricle). UA or USA – Unstable Angina: Chest pain that occurs when diseased blood vessels restrict blood flow to the heart; symptoms are not relieved by rest; considered a dangerous and emergency crisis requiring immediate medical help. Valves: Your heart has four one-way valves that keep blood flowing in the right direction. Blood enters the heart first through the tricuspid valve, and next goes through the pulmonary valve (sometimes called the pulmonic valve) on its way to the lungs. Then the blood returning from the lungs passes through the mitral (bicuspid) valve and leaves the heart through the aortic valve. Vasodilator: A drug that causes dilation (widening) of blood vessels. Vasospasm: A blood vessel spasm that causes sudden constriction, reducing its diameter and blood flow to the heart muscle. See also Prinzmetal’s Variant Angina. VB – Ventricular Bigeminy: A heart rhythm condition in which the heart experiences two beats of the pulse in rapid succession. Vena Cava – a large vein that carryies de-oxygenated blood into the heart. There are two in humans, the inferior vena cava (carrying blood from the lower body) and the superior vena cava (carrying blood from the head, arms, and upper body). Ventricle – each of the two main chambers of the heart, left and right. VF – Ventricular Fibrillation: A condition in which the ventricles (two lower chambers of the heart) contract in a rapid, unsynchronized fashion. When fibrillation occurs, the ventricles cannot pump blood throughout the body. Most sudden cardiac deaths are caused by VF or ventricular tachycardia (VT). VLDL – Very Low Density Lipoprotein: Molecules made up of mostly triglycerides, cholesterol and proteins. VLDL, also known as the “very bad” cholesterol, carries cholesterol from the liver to organs and tissues in the body. It may lead to low density lipoproteins (LDL), associated with higher heart disease risks. VLDL levels are tricky to measure routinely, and are usually estimated as a percentage of your triglyceride levels. By reducing triglycerides, you are usually also reducing your VLDL levels. VT or VTach – Ventricular Tachycardia: An arrhythmia (abnormal heartbeat) in the ventricle usually seen as a very fast heartbeat. Most sudden cardiac deaths are caused by ventricular tachycardia (VT) or ventricular fibrillation (VF) Warfarin – A drug taken to prevent the blood from clotting and to treat blood clots. Warfarin is believed to reduce the risk of blood clots causing strokes or heart attacks. Also known as Coumadin. Widowmaker heart attack – The type of heart attack I survived, since you asked. A nickname doctors use to describe a severely blocked left main coronary artery or proximal left anterior descending coronary artery of the heart. This term is used because if the artery gets abruptly and completely blocked, it can cause a massive heart attack that will likely lead to sudden cardiac death. Please note the gender imbalance here: despite the number of women like me who do experience this type of cardiac event, doctors are not calling this the widowermaker, after all. . . WPW – Wolff-Parkinson-White Syndrome: A condition in which an extra electrical pathway connects the atria (two upper chambers) and the ventricles (two lower chambers). It may cause a rapid heartbeat. Yamaguchi Syndrome, Yamaguchi Hypertrophy – see A-HCM Sources: Cleveland Clinic, Heart and Stroke Foundation, Texas Heart Institute, Ottawa Heart Institute, Mayo Clinic, UpToDate® Are we missing any important heart acronyms/terms from this list? Let me know! Last revised July 11, 2019	2	11	0	0	0	1	0.919761	1	13,444
The World Health Organization (WHO) made waves earlier this year by including an entry for “Gaming Disorder” in their plans for the 11th International Classification of Diseases (ICD-11). The fault line for the current debate does not seem to concern whether excessive gaming/screen time is a problem in our society—undeniably, it is. The question is whether said overuse can be categorized as a “disorder” in the technical sense of the word: an abnormal condition, something that disrupts one’s life, health, and well-being. Having read the draft’s diagnostic criteria, which includes “continuation or escalation of gaming despite the occurrence of negative consequences” and a minimum onset/development time of 12 months, I am skeptical. I am not the only one concerned by the specificity of the label. By training, I am a Social Worker; by profession, I am a therapist, not a psychiatrist. However, with a Master’s degree in Social Work, I am comfortable reading and understanding the diagnostic criteria of not only the WHO’s ICDs (currently on its 10th revision, or ICD-10), but perhaps more importantly the 5th Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published by the American Psychiatric Association (APA). Unlike the ICD, which attempts to codify all diseases and injuries, the DSM focuses specifically on mental and behavioral health. Its own codifying and diagnosing tends to—sometimes making intentional attempts to—match the ICD. At other times, these two Bible-sized documents butt heads. Considering the WHO is already committed to declaring Gaming Disorder a Real Thing™, the question remains whether the APA will go the same way in the next edition if the DSM. There is no precedent to suggest they will go in one direction or the other. In the DSM, addiction tends to be broken into two categories: substance and process. The latest jargon for substance addiction is “Substance Use Disorder,” a linguistic change that intentionally divorces dependence from disorder—dependence being considered neutral, while disorder suggests a form of dependence that causes problems for the individual’s health or well-being. Doing so gives a pass to the millions (billions?) of humans who are likely dependent upon caffeine, as evidenced by withdrawal symptoms should they stop caffeine intake. More on this later, as it’s relevant to the discussion. The DSM’s other primary type of addiction, the process addiction, is equivalent to what the WHO/ICD categorizes as “behavior addictions.” The three criteria driving the labeling of a process/behavior addiction as such are: (1) addictive behavior [x] increases over time in the person’s life; (2) the person can’t stop doing behavior [x] even when they try; (3) the results of behavior [x] is causing harm to the person or others around them. Generally, substance addiction has all of these markers as well, with the added criteria that the substance tends to cause a physiological/chemical dependency, which is not the case for process disorders. Presently, the only process addiction identified in the DSM-5 is Gambling Disorder. Other frequently-acknowledged process addictions in society—sex, shopping, eating, and now gaming and internet use—can be found elsewhere throughout the DSM. For example, an “addiction to eating” would likely be categorized as BED (Binge Eating Disorder), which falls under the category of eating disorders, not addictions. Compulsive/impulsive sex and shopping may be acknowledged as symptoms of a manic phase in bipolar disorder, or the result of other complex factors. At the time of the DSM-5’s publishing, the DSM includes a special area called “Section III.” It’s not quite as cool as Area 51, but it is the forefront of the psychological scene, as this is the area where the APA is essentially calling for more research. And, yes, this is where the DSM currently holds gaming disorder: in the “we need more information” zone. And, even though the DSM-5 was first published in 2013, updates to the current version and publication of the next version take time—by which I mean decades (DSM-III first published 1980, DSM-IV first published 1994). To date, DSM-5 has only had one supplemental release added. It was in October 2017, and it did not address Gaming Disorder. Rather, the much-needed update addressed the current opioid epidemic and other substance use disorders. Specifically, “Internet Gaming Disorder” is what the DSM-5 is considering (as opposed to the WHO, which is proposing a generalized Gaming Disorder that does not require the component of online interaction). Also listed in Section III: “Caffeine Use Disorder.” The editors of the DSM are on the fence about caffeine for a few obvious reasons: (1) for most people, caffeine intake is not progressive (increased tolerance, yes, but not progressive over a lifetime); (2) while withdrawal symptoms can be uncomfortable, individuals who wish and/or need to remove caffeine from their lives can do so without the cravings associated with nicotine, alcohol, and narcotics; (3) caffeine is everywhere in the United States, sometimes intentionally added by a food/beverage producer, other times naturally occurring in the product. As a process addiction, I can very much see the term “disorder” used as a valid descriptor for what we have seen in worst-case scenario reports about reclusive lifestyles, untimely death, and more in relation to gaming. And certainly, attempts at treatment have already begun in countries all around the world: from support groups and 12-step “anonymous” groups to formal and targeted treatment programs in South Korea and Japan, the healers of our planet are trying to work through this. So, yes, maybe gaming disorder is a disease.Here is my request to the mental health community: it’s time to go all-or-none on process addictions. But, still worthy of note: sex addiction, shopping addiction, addiction to internet pornography, and more, are not specified in either the ICD-10 or the DSM-5. My theory? The sea change from one generation to the next, the astonishment and horror at how much time our youth can spend in front of a screen, is prompting a counter-reaction to explain it as not only abnormal but highly detrimental. To provide context, imagine you time travel from 400 AD to the present time. The notion that people could even have time to be addicted to vices such as over-spending or looking at images of nude people for pleasure would be shocking. For those many generations, these problems already existed. The novelty of the all-engaging screen-based entertainment format is what seems to horrify older generations. Some in my generation and even younger, self-aware enough to see what’s going on with smartphones alone, can see how technology is changing us, for better or worse. To call it a disorder makes sense in this context if society cannot function around it. The time traveler and the grandfather point and scream, “what sorcery is this?!” However, if society adapts to the dependence on the technology, as society has also adapted to dependence on caffeine, it may no longer be appropriate to consider the language of disorder. Here is my request to the mental health community: it’s time to go all-or-none on process addictions. Codify all the well-known, easily-identified behavioral addictions and begin to develop diagnostic criteria and targeted treatments for all. Alternatively, remember that you yourselves have developed “Unspecified” ICD codes specifically for F63 (impulsive) and F69 (other unspecified behavioral disorders). It’s what the mental health and social service industries use when coding for sex addiction. Why not leave gaming there as well? Do the numbers suggest one is significantly larger a public health problem than the others? Do we have those numbers? Not yet. A quick search of PubMed Clinical Trial research articles only nets two results for gaming addiction, but nets over four hundred results for gambling. Worthy of note: a search for Clinical Trial research on sex addiction and compulsive sexual behavior nets results only slightly larger than the few results found on gaming addiction, further justifying the stance that we as a society are not ready to specify these behavioral disorders. We do not have all the necessary information to develop specific treatments. Until then, a friendly mental health reminder: be aware of your actions, how you spend your time, and how it affects others. In living a balanced life, we can avoid a bevy of pitfalls laid by the world and our own psyches.	2	2	0	0	0	2	0.793138	2	1,841
Typical and atypical torsional alignment of the legs Pigeon toes, an in-toeing gait, femoral anteversion and tibial torsion are different types of atypical torsional alignment of the thighs, knees and feet that occur in children, and are linked to bone growth as well as the strength, flexibility and coordination of the leg and foot muscles. Femoral anteversion and lateral tibial torsion are commonly seen in children with joint hypermobility. In some children atypical torsional alignment is associated with a neurological disorder such as cerebral palsy or a bone disorder such as club foot. Good thigh and lower leg alignment A child with good leg alignment stands with the knees facing forwards and the feet parallel or turned slightly outwards. There is a slight angle between the thighs and the lower legs. Knees and feet turned inwards when standing (in-toeing) A child may stand with both the knees and the feet turned inwards. If this is the case, then the problem may be caused by: - tightness and weakness in the hips muscles that limit the external rotation (outwards twist) of the hip joint; - an increase in the normal small amount of torsion (twist) in the femur - referred to as femoral anteversion. (See below.) Knees forwards, feet turned inwards: medial tibial torsion If the child stands with the knees facing forwards but the feet turned inwards, the problem lies in the rotation movements of the knees, which may also be associated with an abnormal twist in the tibia (tibial torsion). Knees facing forwards, feet turned out (lateral tibial torsion) There are also quite a number of children who stand with feet turned outwards. This outwards twist is know as lateral tibial torsion. In many children the outwards twist is related to excessive outwards rotation of the knee, along with limited inwards rotation. Children who walk on their toes often have lateral tibial torsion associated with tightness in the iliotibial band. Read more: Idiopathic toe walking. Knees turned in, feet parallel (lateral tibial torsion) Other children stand with the knees turned in, but the feet facing forward. If this is the case, the child has a combination of medial femoral torsion and lateral tibial torsion. The degree of tibial torsion can best be seen when the child is instructed to stand with the knees facing directly forwards, If tibial torsion is present the feet will be positioned outwards. W-sitting contributes to lateral tibial torsion Lateral tibial torsion is exaggerated in children who habitually sit between the legs (w-sitting). In this position the knee joints are forced into extreme degree of outwards rotation. What is an in-toeing gait? A child is said to have an in-toeing gait when he/she walks with the feet turned inwards. The footprints of a child with good leg alignment, are angled a few degree away from the line of progression. The footprints of a child with an in-toeing gait are angled towards the line of progression. In-toeing gait is associated with anteversion of the hips as well as hip muscle weakness and tightness. Hip movements in children who are pigeon-toed In a typically developing child, aged of 5-6 years, the rotation (twisting) movement at the hip joint allows 45 degrees in both directions. This movement is tested with the child lying on the tummy, with the hips fully extended, the thighs parallel and the knee flexed to 90 degrees. The lower leg is moved to the left and the right. Typically, by the age of 7-8 years children have about 45 degrees of both lateral and medial rotation. (Sutherland 1988). Children with in-toeing (pigeon toes) typically have increased internal (inward) rotation of the hip, often as much as 70-80 degrees, and very limited external rotation (usually only 10-20 degrees.) What is femoral anteversion? When a typical femur (thigh bone) is placed on a table, the lower end of the femur lies flat on the surface, and the head and neck of the femur are angled forwards slightly. This slight twist in the femur, technically known as femoral torsion, means that when standing erect with the hips in extension the knees face straight forwards. In some children the amount torsion in the femur in increased, so that the angle between a line through the head and neck of the femur and a line through the lower end of the femur increases from a typical 8-10 degrees to 30-40 degrees. This twist in the femur means that when the head of the femur fits neatly into the hip socket (acetabulum), the knees are turned inwards. Infant femurs are naturally anteverted At birth the angle between the head and neck and the lower end of the femur is large (30-40 degrees). In other words infants are born with femoral anteversion. This degree of anteversion is linked to the flexed position of the infant in the womb. In fact, a full term infant's hips cannot be fully extended. As the infant grows and develops better hip extension, and then starts to walk and becomes more active, the anteversion angle decreases, until it reaches the mature values of 8-10 degrees in adults. This normal deroration of the femur depends on strong and balanced action of the hip muscles, in lying, standing and walking. Link between femoral anteversion and increased hip medial rotation In most instances, a child who has a large angle of femoral anteversion, will also have increased hip internal rotation, with decreased external rotation. However, recent research, using MRI scans to confirm femoral anteversion, have shown that the association between the angle of anteversion and the range of hip internal rotation is variable. This means that a child with a very large range of hip internal rotation may not have excessive femoral anteversion. Femoral anteversion can only reliably be diagnosed with an MRI or CT scan. A diagnosis cannot be made solely on the basis of increased hip internal rotation or an in-toeing gait. How in-toeing affects standing on one leg By the age of 5-6 typically developing children can stand on one leg with the the trunk upright and balanced over the standing leg. The knees and feet face forwards, and the child uses small movements of the foot to maintain balance. Children with limited range of hip external rotation, along with some tightness in the iliotibial band and weakness of the buttock muscles have difficulty standing on one leg with good alignment. The pelvis and trunk tilt sideways and the knees tend to turn inwards. The child uses hip and trunk movements to maintain balance, rather than the more effective small ankle movements. In-toeing and the swing phase of gait Children who walk with the feet twisted inwards usually have difficulties with controlling the position of the foot as the leg is moved forwards to take the next step. The thigh and the foot are turned inwards as the leg is moved forwards and placed down on the floor. This inwards twist of the leg is associated with weakness of the hip muscles that flex and rotate the hip joint. Try the following The difficulties a child experiences with controlling the rotation of the hip in walking, can be seen when a child is asked to lie on the back, lift one leg to 450 and hold the position for 20 seconds. If the child has good strength in the hip flexor muscles the knee will face upwards and the position can be easily maintained for the full 20 seconds. If the hip flexor muscles are weak child tends to twist the leg inwards so that the knee faces inwards as the muscles get tired. Does in-toeing improve over time? Orthopedic surgeons tend to recommend a wait-and-see approach for young children presenting with in-toeing gait The expectation is that the degree of in-toeing will decrease over time and have corrected itself by the age of 8-10 years. And indeed research has shown that the degree of in-toeing when walking does often improve over time. However the tendency for the thighs to be twisted inwards with the knees turned towards each other when standing and walking may still be present, even when the feet are not turned inwards when standing and walking. This is because the child compensates for the inwards twist of the thigh by twisting the lower leg outwards at the knee joint. In-toeing associated with femoral anteversion If the in-toeing is severe and interferes with function, and there is marked anteversion of the femur, the child's orthopedic surgeon may recommend a derotation osteotomy to correct the twist in the femur. An MRI or CT scan is needed to establish a diagnosis of anteversion of the femur. It is important to note that while in most cases and increased anterversion angle is usually associated with excessive internal rotation of the hip, this may not always be the case. (Kim et al 2011) The opposite is also true, a large angle of hip internal rotation does not necessarily mean that femoral anteversion is present. In severe cases of femoral anteversion, most often seen in children with cerebral palsy a derotation osteotomy improves the biomechanics of the hip joint and allows the muscles to start working more effectively when walking. Can exercises improve in-toeing? An exercise program to improve the weakness and tightness of the hip muscles can improve not only the degree of in-toeing in standing and walking, but also improve the child's ability to perform gross motor tasks that involve walking, running, balance and jumping. An exercise program is particularly helpful when the degree of anteversion is not severe, and may even help to accelerate the normal reduction in the angle of anteversion which occurs over time. It must be kept in mind that an exercise program while improving strength, flexibility and function will probably not affect severe femoral anteversion to any degree. However, if a deroration osteotomy is being considered, improving a child's strength, flexibility and function before surgery will improve the outcome. An effective exercise program should include stretching, strengthening and coordination exercises. SfA Training Guide Fitness Program for In-toeing Gait This program includes exercises designed to improve the impaired flexibility, muscle strength and coordination commonly experienced by children who stand and walk with in-toeing. Children will only participate in an exercise program if it is interesting, there is a bit of a challenge and they experience success. All exercises start with an easy version and provide instructions for increasing the difficulty. Hip muscle stretching exercises to improve the ability to extend and laterally rotate the hip joint Standing on one leg exercises: to improve the ability to stand on one with good pelvic and leg alignment. Hip flexion exercises: to improve the child's ability to lift the leg forwards with the foot straight. Walking exercises: to improve foot placement, balance and coordination. Subscribe to the SfA Training Guide for access to these exercise instructions Includes PDF files for home exercise programs (HEPs). Disclaimer: The content on this site is provided for general information purposes only and does not constitute professional advice. Botser IB, Ozoude GC, Martin DE, Siddiqi AJ, Kuppuswami S, Domb BG. Femoral anteversion in the hip: comparison of measurement by computed tomography, magnetic resonance imaging, and physical examination. Arthroscopy. 2012 May;28(5):619-27. doi: 10.1016/j.arthro.2011.10.021. Epub 2012 Feb 1. PubMed PMID: 22301362. Sielatycki JA, Hennrikus WL, Swenson RD, Fanelli MG, Reigha J, Hamp JA. In-Toeing Is Often a Primary Care Orthopedic Condition. J Pediatr. 2016 Jul 25. pii: S0022-3476(16)30382-1. doi: 10.1016/j.jpeds.2016.06.022. [Epub ahead of print] PubMed PMID: 27470689. MacWilliams BA, McMulkin ML, Davis RB, Westberry DE, Baird GO, Stevens PM. Biomechanical changes associated with femoral derotational osteotomy. Gait Posture. 2016 Jul 1;49:202-206. d Sutehrland DH et al (1988) The Development of Mature Walking. Mac Keith Press Mooney JF 3rd. Lower extremity rotational and angular issues in children. Pediatr Clin North Am. 2014 Dec;61(6):1175-83. Kim HD, Lee DS, Eom MJ, Hwang JS, Han NM, Jo GY. Relationship between Physical Examinations and Two-Dimensional Computed Tomographic Findings in Children with Intoeing Gait. Ann Rehabil Med. 2011 Aug;35(4):491-8. Radler C, Kranzl A, Manner HM, Höglinger M, Ganger R, Grill F. Torsional profile versus gait analysis: consistency between the anatomic torsion and the resulting gait pattern in patients with rotational malalignment of the lower extremity. Gait Posture. 2010 Jul;32(3):405-10. doi: Howlett JP, Mosca VS, Bjornson K. The association between idiopathic clubfoot and increased internal hip rotation. Clin Orthop Relat Res. 2009 May;467(5):1231-7.	2	8	1	0	1	0	0.56663	2	2,952
Taxonomic classification of mental disorders Article published in original Lithuanian language: Psichiatrijos žinios 2020;68:21-25. International presentation in English: EPA 2022, 30th European Congress of Psychiatry. - DSM-5, ICD-10, and ICD-11 classifications can be described as „incoherent“. - Psychopathology depends on “time of damage and resilience” ratio. - Continuums of mental disorders compose a table, like a periodic table of chemical elements. - Similar psychopathology can have different neurobiological origin, and vice versa. Current classifications of mental disorders ICD-10, DSM-5, as well as the new ICD-11 being developed, do not show interrelations in pathogenesis between groups of mental disorders. This is a weak point of these classifications, although they serve a good purpose in relation to medical statistics and encoding requirements. Taxonomic classification of mental disorders proposed in this empirical study reveals interrelations between diagnostic categories of mental disorders. Classification as an object of this empirical study is initially developed on observation of psychopathology in clinical practice. It also relies on scientific data of genetics and neurobiology of mental disorders. The classification is based on two axes system. First axis reflects the time of damage of neural tissue in specific stage, i.e. neuron body genesis, neuron growths genesis, synaptic pruning or further neural information modeling. The second axis is connected with resilience. The two axes system includes in one continuum and connects into one classification table almost all diagnostic groups from ICD-10 or DSM-5 (with two exclusions: “organic” type mental disorders and pathology of myelination process). This empirically derived new concept of classification could be used in clinical practice in differential diagnosis, discovering heterogeneities in patients with same diagnostic “code”, planning treatment strategies, predicting course of mental disorders. This new concept could also be useful in the molecular psychiatry area, hereby connecting molecular psychiatry findings to clinical psychopathology. Mental disorders, classification, ICD-10, DSM-5, taxonomy, neurogenesis. The current International Classification of Diseases 10 (hereinafter referred to as “ICD-10”) and the Diagnostic and Statistical Manual 5 (hereinafter referred to as “DSM-5”), as well as the new ICD-11 classification of mental disorders being developed, are of descriptive-syndromological nature and do not link isolated groups of mental disorders. These two classifications, which are widespread throughout the world, are well suited to medical statistics, where the institutions supervising the work of mental health professionals require that the mental disorder being treated and some kind of diagnostic-statistical category be necessarily “inserted”. Another feature of ICD-10 and DSM-5 is that groups of mental disorders are distinguished based on different criteria that characterize that group. Looking for a common classification criterion for all groups, we should describe these classifications as “incoherent”: some mental disorders are grouped according to their origin (e.g., ICD-10 “F0 – Organic, including symptomatic, mental disorders”, ICD-11 “6A0 – Neurodevelopmental disorders”), the second ones are grouped according to prevalent psychopathology (e.g., “F3 – mood disorders”), and the third ones – according to the time of their occurrence (e.g., “F9 – Behavioural and emotional disorders with onset usually occurring in childhood and adolescence”). These weak aspects of ICD-10 and DSM-5 have been discussed in scientific articles . Looking at the classification of mental disorders from a historical point of view, it can be seen that a certain artificial dichotomous approach was sown by the ideas offered in the works of E. Kraepelin in 1883-1899. E. Kraepelin stated that affective disorders and certain forms of mental disorders now attributed to schizophrenia are separate mental disorders (in the original writings of E. Kraepelin, these two separate groups of disorders are called manic-depressive insanity and dementia praecox ). However, the lack of clear boundaries between mental disorders and the question of the continuum of these disorders have arisen for many researchers in psychopathology – for example, it was raised by K. Conrad (1950) , G. Gross and G. Huber . Other researchers who have studied large groups of people with mental disorders have found a genetic link between the disorders . The boundaries artificially drawn by experts between groups of mental disorders may be more convenient for mental health professionals in their clinical work, but they do not reflect the pathogenetic relatedness of mental disorders. The first criterion for taxonomic classification: the time of damage to the central nervous system In nature, there is a general principle of biological development – the development of the individual, which has started since the emergence of zygote, takes place at a faster pace, then slows down exponentially . The earlier the lesion, the more pronounced and stable the pathological changes in the body. This principle is universal in nature – for example, if the tree is damaged at the seedling stage, pronounced deformations may persist throughout the observed structure of the grown tree. The time of damage to the central nervous system (CNS) would be the first of the two criteria of the classification scheme proposed in the article. I will remember the evolution of neurons in the CNS – see Figure 1. Fig. 1. Development of cerebral neurons The reference years of the periods are approximate because the CNS develops non-homogeneously, e.g., pyramidal neurons are fully formed before human birth, while interneuron formation continues after birth . In one area of the CNS, axons may grow in a certain period of time, and in another, synapses may already form . Individual differences in the CNS development schedule are also possible (e.g., gender depended). From the emergence of zygote to birth, marked in Figure 1 as “0 years”, neuronal bodies develop – let’s call this process neurosomatogenesis. In 0-3 years, neuronal outgrowth branches, i. e. neurites (axons and dendrites) – neuritogenesis occurs. In 3-6 years, new neuronal synapses, interneuronal network are formed – synaptogenesis takes place. In 6-14 years, synapses are restructured, a part of them is removed – synaptodeletion takes place. During this period, there is an intense process of synaptic “pruning”, during which about 2/3 of the former synapses remain in the CNS [8,9]. By about 14 years of age, the CNS neural network has already been formed, and further modeling of the stored information in the formed neurons is underway. Special mention should be made of the process of myelination of the nervous system, which, in contrast to the genesis of neuronal bodies and growths, only accelerates in childhood . Thus, one, and perhaps essential, criterion on which CNS activity will depend later in life is the period (neurosomatogenesis, neuritogenesis, synaptogenesis, synaptodeletion, or information modeling) in which the damage was caused by stressogenic factors. This would be the first of the two criteria for the classification scheme proposed in the article. Severe lesions occurring within the intrauterine stage almost completely block the further development of the CNS – it stops completely in the early stages of development. Subsequent ones, meanwhile, do not have such an all-encompassing deterrent effect, but direct the development of the CNS in a pathological direction. Subsequent stressogenic events in life amplify this effect to clear clinical forms. The second criterion of taxonomic classification: CNS resilience The second criterion of the classification scheme presented in the article is the resilience of the CNS to stressogenic factors. This resilience could be divided into two opposing subcategories: the strength of stressogenic factors, their intensity versus the ability of neurons to repair stress-induced neurotransmitter deficiency (it may be a genetically predisposed trait) . Thus, four combinations of resilience subcategories are possible: intense, strong harmful effects and low neuronal recovery reserve (neuronal damage is greatest and beyond a certain damage threshold may be irreversible), weak harmful effects and high neuronal recovery reserve (damage will be minimal); and intermediate variants – strong harmful effect against strong neuronal recovery reserve and weak harmful effect against weak neuronal recovery reserve. However, in order to simplify this classification and avoid its three-dimensional representation (this would give three axes: evolutionary axis, axis of strength of stressogenic factors, neuronal recovery potential axis), the strength of stressogenic factors and neuronal recovery potential are combined into a common “resilience” axis. The article refers to the stage of decompensation of changes in the body caused by stressogenic factors damaging CNS or other organ systems during stress. Describing non-specific reactions of the body to harmful factors, H. Selye named this stage as “distress” . Harmful effects of of stressogenic factors are understood here as a stage of prolonged stress, depleting the biological resources of the CNS, including neurotransmitters (serotonin, dopamine, noradrenaline, glutamate etc.) and a reserve of growth factors in neurons. Pre-natal stressogenic factors are mostly biological. The intrauterine influence of psychological factors is also unquestionable, however, more data are still lacking on how exactly they affect fetal development. After birth, psychosocial factors contribute to biological harmful factors, and biological ones in turn cause psychosocial stress to the individual. To illustrate the phenomenon of resilience, I will use a picture from S. M. Stahl’s book “Stahl’s Essential Psychopharmacology” – see Figure 2 . Fig. 2. Resilience vs harmful factors The strength of the bridge structure would correspond to the resilience of the CNS (S. M. Stahl writes in his book that they are mainly gene-dependent), and the weight of the car or truck driving on the bridge would correspond to the strength of the stressogenic effect, a heavier vehicle would correspond to a stronger harmful effect. Thus, Figure 2.1. depicts a condition in which the “bridge” of CNS neurons is strong enough and the object passing through it is relatively light – therefore there is no potential for damage. Figure 2.2. would correspond to the condition when the bridge is resistant, but a particularly heavy object passes through it – a damage to the integrity of the bridge occurs, but the bridge, although with deformations, still withstands it. Figure 2.3. would correspond to the condition when the defect of the bridge structures is sufficiently pronounced and a light object passes through it – as in the case of Figure 2.2, a damage occurs, but the bridge withstands the harmful effects with deformations. Figure 2.4. illustrates the bridge that has lost its strength and at the same time is exposed to a severe damaging factor. In this case, the CNS “bridge” structure is severely damaged, even irreversible damages are possible. Description of the classification scheme The proposed taxonomic classification scheme for mental disorders, presented in Figure 3, is based on the system of the two axes described above. One axis reflects the effect of stressors on CNS development, the other axis reflects CNS resilience. Fig. 3. Taxonomic classification scheme for mental disorders In contrast to ICD-10 or DSM-5, these two axes become a common criterion for almost all mental disorders. The exception would be mental disorders of organic origin (neoplastic, traumatic, ischemic-infarct, neuroinfectious, etc., see below) that can begin at any age. A distinction should also be made between activity and attention disorders, for the pathogenesis of which the CNS myelination process is important (see below). In both the horizontal and vertical directions, mental disorders are interrelated and form horizontal and vertical continuums. In the case of a continuum of disorders, the cell boundaries of the classification scheme are conditional, in reality there are no such clear boundaries. Viewed in the horizontal direction, mental disorders are related qualitatively, i. e. linked by “overlapping” psychopathology, while in the vertical direction they are related quantitatively – linked by the severity and intensity of symptoms. This results in 8 main groups of disorders. During neurosomatogenesis, there is a clinical onset of mental disorders of the group of intellectual development disorders and severe forms of childhood autism. The neurobiological basis of autism, childhood forms of schizophrenia, lies in the period of neuritogenesis. During the period of synaptogenesis characterized by intense changes in the neural network – the basis of later forms of schizophrenia, milder disorders of the schizophrenia spectrum, delusional disorder, obsessive-compulsive and bipolar affective disorder, and later – unipolar depression, anxiety disorders. At the end of the “pruning” phase of synapses, the psychopathology of personality disorders ceases to form. As in the case of the ten main groups of ICD-10, the eight main groups of the taxonomic classification ar further subdivided into subgroups of mental disorders. In this classification scheme, each of the eight groups has three levels. These three levels are distinguished by the severity of group-specific psychopathology. Each level-box of the classification scheme includes several ICD-10 distinguishable mental disorders. The scheme cells of all ICD-10 diagnostic units with their characteristic predominant psychopathological symptoms are not presented, as the aim of Figure 3 is to show the interconnectedness of the eight main groups. For example, a schizoaffective disorder would include a depressive, manic, or mixed type of disorder, and, for example, a “box” of episodic anxiety includes panic disorder, specific phobias, etc. The CNS disorders occurring in the intrauterine period and in the earliest period after birth cause a congenital intellectual disability. As other organ systems are formed at the same time, they can also be damaged, such as defects in the face, eyes, heart septum and valves. The stronger the harmful factors and the weaker the regenerative properties of the CNS, the earlier the development of the CNS stops, the more severe the intellectual development disorder will be. Later we observe more severe forms of childhood autism spectrum disorders that also begin in early childhood. Their expression will depend on the balance of harmful factors: strength versus neural regeneration. During the branching period of neuronal axons and dendrites, the roots of autism and earlier (“core” schizophrenia) and more severe (which will cause schizophrenic personality defect in the future) schizophrenia are likely to lie. During the period of synaptogenesis, episodic schizophrenia, schizotypal, schizophrenia-like (schizophreniform) disorders, schizoaffective disorders, early forms of obsessive compulsive disorder, and later groups of affective and anxiety disorders associated with overlapping affective psychopathology may develop in the presence of harmful factors. Their severity will depend on the individual’s CNS resilience to harmful factors. In contrast to the cases of damage during the stages of neurosomatogenesis and neuritogenesis, the neurobiological basis of mental disorders formed during synaptogenesis does not yet lead to the development of psychopathological symptoms during the damage period. Clear clinical symptoms appear later when an individual is exposed to a recurrent stronger stressogenic factor, usually in adolescence or early adulthood. These recurrent stressogenic factors (usually psychosocial) also “trigger” episodic schizophrenia, obsessive compulsive, affective, or anxiety disorders. This is also influenced by the process of “pruning” of synapses in adolescence. It is possible that the pathology of synaptogenesis later leads to synaptic “pruning” disorders. Personality disorders in the classification scheme are marked at the 6-14 year synapse restructuring- synaptic deletion period. Clearly, personality (i.e., stable, “recorded” patterns of an individual’s relationship) develops from the moment an individual is begun. From the beginning, an individual is always in a real relationship: first in a symbiotic, later in a diadic, even later in a triadic, and so on. Therefore, the taxonomic classification of personality psychopathology should be separate, perhaps also aligned with the stages of CNS development. In the scheme of this article, the 6-14 year period more reflects the stage of “completion” of the neurobiological basis of the personality. In terms of the relationship between psychopathological symptoms and personality structure, severe, early-onset mental disorders inevitably affect all further development of the human personality (e.g., a person with autism or early onset of schizophrenia will automatically become introverted, extraversion becomes impossible for him). Meanwhile, the relationship between later mental disorders and the personality is the opposite – these disorders themselves “flow” from the pathological structure of the personality. When a conflict or deficit of personality with external psychosocial factors occurs, anxiety reactions arise, and as they prolong and deplete the reserve of certain neurotransmitters, accompanying affective psychopathology begins. Such a process is called decompensation of personality traits with the resulting anxiety and mood-affective disorders. In the presence of CNS damage at the synaptogenic stage, i. e. with a predisposition to the psychopathology of the schizophrenia spectrum, acute transient, polymorphic psychotic disorders are possible during decompensation of personality traits. As already mentioned, ICD-10-named “organic” type factors that structurally damage nerve tissue can occur at any time during CNS development. A clinical picture of a localization-dependent damage would be more appropriate for psychopathology induced by organic type factors than a damage time and resilience scheme, so there are no organic structural mental disorders in this classification scheme. Clearly, according to the same principle of development mentioned above, organic brain damage in the early stages of development will inhibit all further mental development. The various psychosomatic symptoms and syndromes, some of which are separated into individual diagnostic categories in the ICD-10 classification, are listed in the generalized anxiety box in this taxonomic classification scheme for simplicity. This combination of various psychosomatic symptoms is based on the assumption that the activity of the vegetative CNS centers in the hypothalamus and thalamus is significantly altered during prolonged anxiety (i.e., the distress mentioned above ). These vegetative CNS centers regulate various body functions – cardiac activity, vascular, urogenital system, gastrointestinal, respiratory tract tone, appetite, sleep, libido, perception of pain and other sensations, etc. (and possibly immune system reactivity). In some cases, the state of pathological generalized anxiety in the limbic system and its associated hypothalamus and thalamus is “converted” (i.e., the conversion mechanism) into symptoms felt in the body: various forms of somatoform autonomic dysfunction of inner organs, somatoform pain disorder, functional muscle spasms, and tics occur. In other cases, a dissociation mechanism opposite to conversion occurs: a certain function of the body is “turned off” by increased anxiety – thus dissociative disorders develop. And the third mechanism of development of psychosomatics – the state of generalized anxiety significantly impairs other functions of the body, such as sleep, appetite, sexual function, causing the corresponding disorders of sleep, sexual function and appetite. Clearly, bodily symptoms of mental disorders occur not only during generalized but also during episodic (paroxysmal-panic, phobic, obsessive) anxiety. As mentioned, the box boundaries of the classification scheme are conditional, the symptoms of adjacent boxes overlap, and thus, the psychosomatic symptoms also pass into the cells of the group of depressive disorders. There is no position of attention and activity disorder of children in this scheme. It may be related to the process of myelination, the evolution of which is different from the development of neuronal bodies, growths, or synapses [6,13]. The basic phases of CNS development also correlate with the stages of personality development determined by psychodynamic theories – the fundamental attachment from birth (J. Bowlby), schizoid-paranoid in the 1-3 year period, depressive stage from 3 years (M. Klein), and separation-individuation in the period of 0-5 years (M. Mahler) . In addition to the mental disorder scheme, a table of normal mental development is provided for comparison. The practical significance of this classification proposal In the daily work of a doctor psychiatrist, mental disorders must inevitably be coded according to ICD-10 or DSM-5, as it is required by the authorities supervising the work of mental health professionals. Of course, these classifications, which are well adapted to medical statistics and accounting, are necessary and useful. However, it is always useful to look at the patient’s mental health problems in a broader sense – such a broader approach is the taxonomic classification of mental disorders. The clinician should not be surprised by overlapping symptoms, i.e. psychopathological symptoms characteristic of a group other than the coded by ICD-10. For example, in the case of bipolar affective disorder closer to the group of schizoaffective disorders, typical symptoms of schizophrenia are also “allowed“. Symptoms of the schizophrenia spectrum may also include childhood-onset obsessive-compulsive disorder. The course of childhood-onset schizophrenia may be characterized by autism spectrum psychopathology and stable cognitive impairment. It is possible that some of the mental disorders identified in the ICD-10 classification are combinations of several taxonomic classifications of mental disorders. For example, addiction to psychoactive substances – these would consist of personality psychopathology (emotional instability, narcissistic personality traits, poor impulse control, etc.) together with anxiety and mood disorders, for the suppression of which the use of psychoactive substances is chosen. E. Bleuler states in the 1934 textbook of psychiatry that “many morphinists ab ovo are psychopaths” . There is currently no clear answer as to whether the use of psychoactive substances (PAS) can cause psychotic disorders in any person using them. E. Bleuler, the creator of the term schizophrenia, described alcohol-induced psychoses in the aforementioned psychiatric manual and suggested that such patients were also likely to have chronic symptoms of the schizophrenia spectrum . This would be in line with the approach presented in this article: in the case of a CNS damage, e.g. at the stage of synaptogenesis, and later until clear clinical symptoms, the mental disorder may be “triggered” by a variety of harmful factors, including the use of PASs. As in the case of addiction to psychoactive substances, the group of eating disorders would consist of a certain personality psychopathology, accompanied by marked specific autoaggression against body itself. Obsessive compulsive disorders (OCD), which I would say would be reasonably excluded in separate DSM-5 classification group, appear to include several different groups of mental disorders in clinical practice. An early onset, which started in childhood or adolescent, in the taxonomic classification is closer to the group of schizoaffective disorder. Early-onset OCD may also be characterized by features of the schizoaffective spectrum – chronic course, pronounced compulsive rituals, possible delusional inclusions, loss of critique of obsessive thoughts, and concomitant affective waves. The later onset form of OCD is associated with a variety of anxiety disorders; it is more common in personalities of an anancastic type. This subgroup of OCD is not characterized by features of the schizophrenia spectrum. Borderline personality disorder, manifested in problems of perception of one’s identity, self-harm, specific experiences of the “emptiness” affect, is often accompanied by waves of affect. Such fluctuations in affect, “poles”, raise the question of the relationship between borderline personality psychopathology and bipolar affective disorder. However, there is more evidence that borderline personality disorder and bipolar disorder are separate mental disorders that are not directly linked by pathogenesis . Somatization disorder in ICD-10 belongs to the group of anxiety disorders, but rather it is a combined psychopathology of a certain type of personality, “supplemented” during decompensation by various, polymorphic (phobic anxiety, generalized anxiety, etc.) psychopathology of anxiety disorders with abundant psychosomatic symptoms. “Psychodynamic Diagnostic Manual (PDM-2)“ by V. Lingiardi and N. McWilliams distinguishes the type of “somatizing personality” . The diagnosis of mixed anxiety and depressive disorder (ICD-10 code F41.2) rather often used in diagnostics would fall into the classification “gap” between unipolar affective and anxiety disorders. The taxonomic classification scheme “allows” the occurrence of several individual mental disorders in one individual, as there may be more than one harmful factor in the time scale of development. For example, damage to the CNS in the early stages of development can lead to a disorder of the schizophrenia spectrum, and damage in the later stages of development can lead to exogenous depression. Thus, against the background of schizophrenic psychopathology, there will be symptoms of unipolar depression – and these may be two separate mental disorders. Clearly, in this case, unipolar depression will develop already in the background of schizophrenia, not de novo, and will be characterized by specific psychopathology. Or, if the psychopathology of depression is strong enough – as a provocative factor it will lead to an exacerbation of schizophrenic psychosis. Thus, some mental disorders have separate diagnostic codes in ICD-10 or DSM-5 but belong to one “shelf” of taxonomic classification (e.g. a number of somatoform disorders). Some diagnostic categories from ICD-10 or DSM-5 may have similar psychopathology, but belong to different taxonomic group according to pathogenetic process (e.g. obsessive-compulsive disorder and anancastic personality disorder). Some diagnostic categories belong to different sections of ICD-10 or DSM-5 but they are interrelated by pathogenetic process (e.g. bipolar I, II and III types; severe forms of autism and early onset schizophrenia). Some separate diagnostic categories from ICD-10 or DSM-5 are combinations of two or more mental disorders (e.g. dependencies to psychoactive substances, somatization disorder). I hope that this article will stimulate a discussion among professionals about the benefits and attractiveness of such a classification, and will complement it with new insights or data from neurobiology research. Instead of the end – from the fairy tale “Sleeping Beauty” <…> “The fairies began handing out magical gifts to the princess. The youngest fairy gave her beauty, the second – mind, the third – grace, the fourth – the ability to dance, the fifth – to sing, the sixth – to play music. Finally it was the turn of the old fairy. She said: – The young princess will one day prick her finger on a spindle of a spinning wheel and die. All the people gathered began to tremble. But the seventh fairy, who had not given a gift, said: – I cannot remove the incantation, the princess will prick her finger in the spindle, but she will not die, she will fall asleep and sleep for a hundred years. Eventually the prince will come and wake her up.” <…> Declaration of Interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Original article was published in Lithuanian language: Šablevičius M. Psichiatrijos žinios 2020;63:21-5. 1. Adam D. Mental health: on the spectrum. Nature 2013; 496:416-8. 2. Heckers S, Kendler KS. The evolution of Kraepelin’s nosological principles. World Psychiatry 2020;19(3):381-8. 3. Beer MD. Psychosis: A history of the concept. Compr Psychiatry 1996;37(4):273–91. 4. Gross G, Huber G. Ilgalaikės schizofreninių ir jiems būdingų sutrikimų baigtys. Kritinė apžvalga. Biologinė psichiatrija ir psichofarmakologija 2002;4(1):20-7. 5. Marshall M. The hidden links between mental disorders. Nature 2020;581:19-21 6. Catts VS, Fung SJ, Long LE, Joshi D, Vercammen A, Allen KM, et al. Rethinking schizophrenia in the context of normal neurodevelopment. Front Cell Neurosci 2013;7:60. 7. Lim S, Kaiser Developmental time windows for axon growth influence neuronal network topology. Biol Cybern 2015;109(2):275–86. 8. Ackerman S. The Development and Shaping of the Brain. Washington (DC): National Academies Press; 1992. 6 ch. 9. Kalil K, Dent Branch management: mechanisms of axon branching in the developing vertebrate CNS. Nat Rev Neurosci 2014;15(1):7–18. 10. Feldman R. What is resilience: an affiliative neuroscience approach. World Psychiatry 2020;19:132-50. 11. Selye H. Stress and distress. Compr Ther 1975;1(8):9-13. 12. Stahl SM. Stahl’s Essential Psychopharmacology. 3rd ed. New York: Cambridge University Press; 2008. 188-9 p. 13. Lesch KP. Can dysregulated myelination be linked to ADHD pathogenesis and persistence? J Child Psychol Psychiatry 2019;60(3):229:31. 14. Andrikienė L, Laurinaitis E, Milašiūnas R. Psichoanalitinė psichoterapija. Vilnius: Vaistų žinios; 2013. 209-33 p. 15. Bleuler E. Textbook of Psychiatry. New York: The Macmillan Company, 1934. 356 p., 344-5 p. 16. Ghaemi SN, DalleyS, Catania C, Barroilhet Bipolar or borderline: a clinical overview. Acta Psychiatr Scand 2014;130:99-108. 17. Lingiardi V, McWilliams N. Psychodynamic Diagnostic Manual, Second Edition: PDM-2. New York: The Guilford Press; 2017. 42-4 p. 18. Mano pasakų lobynas. Iš prancūzų kalbos vertė Margarita Šeškuvienė ir Vita Malinauskienė. 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Mania, also known as manic syndrome, is a mental and behavioral disorder defined as a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together with lability of affect." During a manic episode, an individual will experience rapidly changing emotions and moods, highly influenced by surrounding stimuli. Although mania is often conceived as a "mirror image" to depression, the heightened mood can be either euphoric or dysphoric. As the mania intensifies, irritability can be more pronounced and result in anxiety or anger. \|Other names\|\|Manic syndrome, manic episode\| \|Graphical representation of mania, cyclothymia and hypomania\| The symptoms of mania include elevated mood (either euphoric or irritable), flight of ideas and pressure of speech, increased energy, decreased need and desire for sleep, and hyperactivity. They are most plainly evident in fully developed hypomanic states. However, in full-blown mania, they undergo progressively severe exacerbations and become more and more obscured by other signs and symptoms, such as delusions and fragmentation of behavior. Causes and diagnosisEdit Mania is a syndrome with multiple causes. Although the vast majority of cases occur in the context of bipolar disorder, it is a key component of other psychiatric disorders (such as schizoaffective disorder, bipolar type) and may also occur secondary to various general medical conditions, such as multiple sclerosis; certain medications may perpetuate a manic state, for example prednisone; or substances prone to abuse, especially stimulants, such as caffeine and cocaine. In the current DSM-5, hypomanic episodes are separated from the more severe full manic episodes, which, in turn, are characterized as either mild, moderate, or severe, with certain diagnostic criteria (e.g. catatonia, psychosis). Mania is divided into three stages: hypomania, or stage I; acute mania, or stage II; and delirious mania (delirium), or stage III. This "staging" of a manic episode is useful from a descriptive and differential diagnostic point of view Mania varies in intensity, from mild mania (hypomania) to delirious mania, marked by such symptoms as disorientation, florid psychosis, incoherence, and catatonia. Standardized tools such as Altman Self-Rating Mania Scale and Young Mania Rating Scale can be used to measure severity of manic episodes. Because mania and hypomania have also long been associated with creativity and artistic talent, it is not always the case that the clearly manic/hypomanic bipolar patient needs or wants medical help; such persons often either retain sufficient self-control to function normally or are unaware that they have "gone manic" severely enough to be committed or to commit themselves. Manic persons often can be mistaken for being under the influence of drugs. In a mixed affective state, the individual, though meeting the general criteria for a hypomanic (discussed below) or manic episode, experiences three or more concurrent depressive symptoms. This has caused some speculation, among clinicians, that mania and depression, rather than constituting "true" polar opposites, are, rather, two independent axes in a unipolar—bipolar spectrum. A mixed affective state, especially with prominent manic symptoms, places the patient at a greater risk for suicide. Depression on its own is a risk factor but, when coupled with an increase in energy and goal-directed activity, the patient is far more likely to act with violence on suicidal impulses. Hypomania, which means "less than mania", is a lowered state of mania that does little to impair function or decrease quality of life. Although creativity and hypomania have been historically linked, a review and meta-analysis exploring this relationship found that this assumption may be too general and empirical research evidence is lacking. In hypomania, there is less need for sleep and both goal-motivated behaviour and metabolism increase. Some studies exploring brain metabolism in subjects with hypomania, however, did not find any conclusive link; while there are studies that reported abnormalities, some failed to detect differences. Though the elevated mood and energy level typical of hypomania could be seen as a benefit, true mania itself generally has many undesirable consequences including suicidal tendencies, and hypomania can, if the prominent mood is irritable as opposed to euphoric, be a rather unpleasant experience. In addition, the exaggerated case of hypomania can lead to problems. For instance, trait-based positivity for a person could make them more engaging and outgoing, and cause them to have a positive outlook in life. When exaggerated in hypomania, however, such a person can display excessive optimism, grandiosity, and poor decision making, often with little regard to the consequences. A single manic episode, in the absence of secondary causes, (i.e., substance use disorders, pharmacologics, or general medical conditions) is often sufficient to diagnose bipolar I disorder. Hypomania may be indicative of bipolar II disorder. Manic episodes are often complicated by delusions and/or hallucinations; and if the psychotic features persist for a duration significantly longer than the episode of typical mania (two weeks or more), a diagnosis of schizoaffective disorder is more appropriate. Certain obsessive-compulsive spectrum disorders as well as impulse control disorders share the suffix "-mania," namely, kleptomania, pyromania, and trichotillomania. Despite the unfortunate association implied by the name, however, no connection exists between mania or bipolar disorder and these disorders. Furthermore, evidence indicates a B12 deficiency can also cause symptoms characteristic of mania and psychosis. Hyperthyroidism can produce similar symptoms to those of mania, such as agitation, elevated mood, increased energy, hyperactivity, sleep disturbances and sometimes, especially in severe cases, psychosis. Signs and symptomsEdit A manic episode is defined in the American Psychiatric Association's diagnostic manual as a "distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration, if hospitalization is necessary)," where the mood is not caused by drugs/medication or a non-mental medical illness (e.g., hyperthyroidism), and: (a) is causing obvious difficulties at work or in social relationships and activities, or (b) requires admission to hospital to protect the person or others, or (c) the person has psychosis. To be classified as a manic episode, while the disturbed mood and an increase in goal-directed activity or energy is present, at least three (or four, if only irritability is present) of the following must have been consistently present: - Inflated self-esteem or grandiosity. - Decreased need for sleep (e.g., feels rested after 3 hours of sleep). - More talkative than usual, or acts pressured to keep talking. - Flights of ideas or subjective experience that thoughts are racing. - Increase in goal-directed activity, or psychomotor acceleration. - Distractibility (too easily drawn to unimportant or irrelevant external stimuli). - Excessive involvement in activities with a high likelihood of painful consequences.(e.g., extravagant shopping, improbable commercial schemes, hypersexuality). Though the activities one participates in while in a manic state are not always negative, those with the potential to have negative outcomes are far more likely. The World Health Organization's classification system defines a manic episode as one where mood is higher than the person's situation warrants and may vary from relaxed high spirits to barely controllable exuberance, is accompanied by hyperactivity, a compulsion to speak, a reduced sleep requirement, difficulty sustaining attention, and/or often increased distractibility. Frequently, confidence and self-esteem are excessively enlarged, and grand, extravagant ideas are expressed. Behavior that is out-of-character and risky, foolish or inappropriate may result from a loss of normal social restraint. Some people also have physical symptoms, such as sweating, pacing, and weight loss. In full-blown mania, often the manic person will feel as though their goal(s) are of paramount importance, that there are no consequences, or that negative consequences would be minimal, and that they need not exercise restraint in the pursuit of what they are after. Hypomania is different, as it may cause little or no impairment in function. The hypomanic person's connection with the external world, and its standards of interaction, remain intact, although intensity of moods is heightened. But those with prolonged unresolved hypomania do run the risk of developing full mania, and may cross that "line" without even realizing they have done so. One of the signature symptoms of mania (and to a lesser extent, hypomania) is what many have described as racing thoughts. These are usually instances in which the manic person is excessively distracted by objectively unimportant stimuli. This experience creates an absent-mindedness where the manic individual's thoughts totally preoccupy them, making them unable to keep track of time, or be aware of anything besides the flow of thoughts. Racing thoughts also interfere with the ability to fall asleep. Manic states are always relative to the normal state of intensity of the affected individual; thus, already irritable patients may find themselves losing their tempers even more quickly, and an academically gifted person may, during the hypomanic stage, adopt seemingly "genius" characteristics and an ability to perform and articulate at a level far beyond that which they would be capable of during euthymia. A very simple indicator of a manic state would be if a heretofore clinically depressed patient suddenly becomes inordinately energetic, enthusiastic, cheerful, aggressive, or "over-happy". Other, often less obvious, elements of mania include delusions (generally of either grandeur or persecution, according to whether the predominant mood is euphoric or irritable), hypersensitivity, hypervigilance, hypersexuality, hyper-religiosity, hyperactivity and impulsivity, a compulsion to over explain (typically accompanied by pressure of speech), grandiose schemes and ideas, and a decreased need for sleep (for example, feeling rested after only 3 or 4 hours of sleep). In the case of the latter, the eyes of such patients may both look and seem abnormally "wide open", rarely blinking, and may contribute to some clinicians' erroneous belief that these patients are under the influence of a stimulant drug, when the patient, in fact, is either not on any mind-altering substances or is actually on a depressant drug. Individuals may also engage in out-of-character behavior during the episode, such as questionable business transactions, wasteful expenditures of money (e.g., spending sprees), risky sexual activity, abuse of recreational substances, excessive gambling, reckless behavior (such as extreme speeding or other daredevil activity), abnormal social interaction (e.g. over-familiarity and conversing with strangers), or highly vocal arguments. These behaviours may increase stress in personal relationships, lead to problems at work, and increase the risk of altercations with law enforcement. There is a high risk of impulsively taking part in activities potentially harmful to the self and others. Although "severely elevated mood" sounds somewhat desirable and enjoyable, the experience of mania is ultimately often quite unpleasant and sometimes disturbing, if not frightening, for the person involved and for those close to them, and it may lead to impulsive behaviour that may later be regretted. It can also often be complicated by the individual's lack of judgment and insight regarding periods of exacerbation of characteristic states. Manic patients are frequently grandiose, obsessive, impulsive, irritable, belligerent, and frequently deny anything is wrong with them. Because mania frequently encourages high energy and decreased perception of need or ability to sleep, within a few days of a manic cycle, sleep-deprived psychosis may appear, further complicating the ability to think clearly. Racing thoughts and misperceptions lead to frustration and decreased ability to communicate with others. Mania may also, as earlier mentioned, be divided into three “stages”. Stage I corresponds with hypomania and may feature typical hypomanic characteristics, such as gregariousness and euphoria. In stages II and III mania, however, the patient may be extraordinarily irritable, psychotic or even delirious. These latter two stages are referred to as acute and delirious (or Bell's), respectively. Various triggers have been associated with switching from euthymic or depressed states into mania. One common trigger of mania is antidepressant therapy. Studies show that the risk of switching while on an antidepressant is between 6-69 percent. Dopaminergic drugs such as reuptake inhibitors and dopamine agonists may also increase risk of switch. Other medication possibly include glutaminergic agents and drugs that alter the HPA axis. Lifestyle triggers include irregular sleep-wake schedules and sleep deprivation, as well as extremely emotional or stressful stimuli. Various genes that have been implicated in genetic studies of bipolar have been manipulated in preclinical animal models to produce syndromes reflecting different aspects of mania. CLOCK and DBP polymorphisms have been linked to bipolar in population studies, and behavioral changes induced by knockout are reversed by lithium treatment. Metabotropic glutamate receptor 6 has been genetically linked to bipolar, and found to be under-expressed in the cortex. Pituitary adenylate cyclase-activating peptide has been associated with bipolar in gene linkage studies, and knockout in mice produces mania like-behavior. Targets of various treatments such as GSK-3, and ERK1 have also demonstrated mania like behavior in preclinical models. Deep brain stimulation of the subthalamic nucleus in Parkinson's disease has been associated with mania, especially with electrodes placed in the ventromedial STN. A proposed mechanism involves increased excitatory input from the STN to dopaminergic nuclei. There are certain psychoactive drugs that can induce a state of manic psychosis, including: amphetamine, cathinone, cocaine, MDMA, methamphetamine, methylphenidate, oxycodone, phencyclidine, designer drugs, etc. The mechanism underlying mania is unknown, but the neurocognitive profile of mania is highly consistent with dysfunction in the right prefrontal cortex, a common finding in neuroimaging studies. Various lines of evidence from post-mortem studies and the putative mechanisms of anti-manic agents point to abnormalities in GSK-3, dopamine, Protein kinase C and Inositol monophosphatase. Meta analysis of neuroimaging studies demonstrate increased thalamic activity, and bilaterally reduced inferior frontal gyrus activation. Activity in the amygdala and other subcortical structures such as the ventral striatum tend to be increased, although results are inconsistent and likely dependent upon task characteristics such as valence. Reduced functional connectivity between the ventral prefrontal cortex and amygdala along with variable findings supports a hypothesis of general dysregulation of subcortical structures by the prefrontal cortex. A bias towards positively valenced stimuli, and increased responsiveness in reward circuitry may predispose towards mania. Mania tends to be associated with right hemisphere lesions, while depression tends to be associated with left hemisphere lesions. Post-mortem examinations of bipolar disorder demonstrate increased expression of Protein Kinase C (PKC). While limited, some studies demonstrate manipulation of PKC in animals produces behavioral changes mirroring mania, and treatment with PKC inhibitor tamoxifen (also an anti-estrogen drug) demonstrates antimanic effects. Traditional antimanic drugs also demonstrate PKC inhibiting properties, among other effects such as GSK3 inhibition. Manic episodes may be triggered by dopamine receptor agonists, and this combined with tentative reports of increased VMAT2 activity, measured via PET scans of radioligand binding, suggests a role of dopamine in mania. Decreased cerebrospinal fluid levels of the serotonin metabolite 5-HIAA have been found in manic patients too, which may be explained by a failure of serotonergic regulation and dopaminergic hyperactivity. Limited evidence suggests that mania is associated with behavioral reward hypersensitivity, as well as with neural reward hypersensitivity. Electrophysiological evidence supporting this comes from studies associating left frontal EEG activity with mania. As left frontal EEG activity is generally thought to be a reflection of behavioral activation system activity, this is thought to support a role for reward hypersensitivity in mania. Tentative evidence also comes from one study that reported an association between manic traits and feedback negativity during receipt of monetary reward or loss. Neuroimaging evidence during acute mania is sparse, but one study reported elevated orbitofrontal cortex activity to monetary reward, and another study reported elevated striatal activity to reward omission. The latter finding was interpreted in the context of either elevated baseline activity (resulting in a null finding of reward hypersensitivity), or reduced ability to discriminate between reward and punishment, still supporting reward hyperactivity in mania. Punishment hyposensitivity, as reflected in a number of neuroimaging studies as reduced lateral orbitofrontal response to punishment, has been proposed as a mechanism of reward hypersensitivity in mania. In the ICD-10 there are several disorders with the manic syndrome: organic manic disorder (F06.30), mania without psychotic symptoms (F30.1), mania with psychotic symptoms (F30.2), other manic episodes (F30.8), unspecified manic episode (F30.9), manic type of schizoaffective disorder (F25.0), bipolar affective disorder, current episode manic without psychotic symptoms (F31.1), bipolar affective disorder, current episode manic with psychotic symptoms (F31.2). Before beginning treatment for mania, careful differential diagnosis must be performed to rule out secondary causes. The acute treatment of a manic episode of bipolar disorder involves the utilization of either a mood stabilizer (carbamazepine, valproate, lithium, or lamotrigine) or an atypical antipsychotic (olanzapine, quetiapine, risperidone, aripiprazole or cariprazine). The use of antipsychotic agents in the treatment of acute mania was reviewed by Tohen and Vieta in 2009. When the manic behaviours have gone, long-term treatment then focuses on prophylactic treatment to try to stabilize the patient's mood, typically through a combination of pharmacotherapy and psychotherapy. The likelihood of having a relapse is very high for those who have experienced two or more episodes of mania or depression. While medication for bipolar disorder is important to manage symptoms of mania and depression, studies show relying on medications alone is not the most effective method of treatment. Medication is most effective when used in combination with other bipolar disorder treatments, including psychotherapy, self-help coping strategies, and healthy lifestyle choices.[medical citation needed] Lithium is the classic mood stabilizer to prevent further manic and depressive episodes. A systematic review found that long term lithium treatment substantially reduces the risk of bipolar manic relapse, by 42%. Anticonvulsants such as valproate, oxcarbazepine and carbamazepine are also used for prophylaxis. More recent drug solutions include lamotrigine and topiramate, both anticonvulsants as well. In some cases, long-acting benzodiazepines, particularly clonazepam, are used after other options are exhausted. In more urgent circumstances, such as in emergency rooms, lorazepam, combined with haloperidol, is used to promptly alleviate symptoms of agitation, aggression, and psychosis. Antidepressant monotherapy is not recommended for the treatment of depression in patients with bipolar disorders I or II, and no benefit has been demonstrated by combining antidepressants with mood stabilizers in these patients. Some atypical antidepressants, however, such as mirtazepine and trazodone have been occasionally used after other options have failed. Society and cultureEdit In Electroboy: A Memoir of Mania by Andy Behrman, he describes his experience of mania as "the most perfect prescription glasses with which to see the world... life appears in front of you like an oversized movie screen". Behrman indicates early in his memoir that he sees himself not as a person with an uncontrollable disabling illness, but as a director of the movie that is his vivid and emotionally alive life. There is some evidence that people in the creative industries have bipolar disorder more often than those in other occupations.[better source needed]Winston Churchill had periods of manic symptoms that may have been both an asset and a liability. English actor Stephen Fry, who has bipolar disorder, recounts manic behaviour during his adolescence: "When I was about 17 ... going around London on two stolen credit cards, it was a sort of fantastic reinvention of myself, an attempt to. I bought ridiculous suits with stiff collars and silk ties from the 1920s, and would go to the Savoy and Ritz and drink cocktails." While he has experienced suicidal thoughts, he says the manic side of his condition has had positive contributions on his life. The nosology of the various stages of a manic episode has changed over the decades. 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Spinal Anatomy, Dr. Guy Home > Flashcards > Print Preview The flashcards below were created by user on FreezingBlue Flashcards . What would you like to do? What connects the lateral ventricle to the third ventricle? Interventricular foramen of monro What does the proencephalon develop into? Telencephalon and Diencephalon What does the mesenceophalon develop into? What does the Rhombencephalon develop into? Metencephalon and Myelencephalon What is the forebrain? What is the Midbrain? What is the hindbrain? List the ventricles in order. Lateral ventricle, third, cerebral aqueduct (aqueduct of sylvius), forth, central canal Where is the lateral ventricles? Where is the third ventricle? Where is the cerebral aqueduct of sylvius? Where is the forth ventricle? Metencephalon and myelencephalon What are the lateral apertures? Where do they go? How many are there? - Foramen of luschka - Into subarachnoid space of the pontine cistern to the spinal canal What are the median aperture? Where do they go? How many are there? - Foramen of Magendie - Into subarachonid space of the cisterna magna (cebebellomedulary cistern) What CN's come from the Telencephalon? What CN's come from the Diencephalon? What CN's come from Mesencephalon? What CN's come from Metencephalon? What CN's come from Myelencephalon? What structures come from the Telencephalon? Cerebrum and higher function What structures come from the Diencephalon? Thalamus, hypophysis, mamillary body What strucutres come from Mesencephalon? Midbrain and everything else What structures come from the Metencephalon? pons and cerebellum What structures come from the Myelencephalon? What are the lateral ventricles? 1st and 2nd ventricles What is the roof of the 4th ventricle? What is the floor of the 4th ventricle? - roof - cerebellum - floor - pons and medulla What reabsorbs the CSF? What separates the lateral ventricles? What produces CSF? Choroid plexus - Ependymal cells which line the ventricles What does the nervous system develop from? dorsal ectoderm, neural plate --> neural groove --> neural fold --> neural tube --> brain and spinal cord What forms the neural crest? Neuroectodermal cells not in the neural tube What does the neural crest develop into? - Schwann Cells - Branchial arches - Adrenal medulla - Meisners plexus - Auerbach plexus - "SMSM BAD MA" What neural tissue is the adenohypophysis derived from? What is the Anterior Pituitary derived from? Rathke's pouch (ectoderm) What is the epithelial lining of the posterior 1/3rd of the tongue, floor of the mouth, soft palate, ducts of the sublingual glands and submandibular glands derived from? What is the epithelial lining of the GI tract derived from? What are Hepatocytes and the epithelial lining of the biliary tree derived from? What are the kidneys, testes, ovaries, genital ducts and accessory sex glands derived from? What are Epidermis, hair, sweat and cutaneous glands derived from? What are acinar cells, islet cells and the epithelial lining pancreatic ducts derived from? What are the skeletal muscles of the limbs derived from? What are CNS derived from? What is the neurohypophysis derived from? What is the neural crest derived from? Ectoderm gives rise to? Nerves and Epidermis Endoderm gives rise to? Respiratory tract and gut Mesoderm gives rise to? Where do pharyngeal pouches develop? In the lateral wall of foregut or pharynx What does the 1st pharyngeal pouch give rise to? Epithelial lining of the auditory tube and middle ear cavity What does the 2nd pharyngeal pouch give rise to? Epithelial lining of the palatine tonsil crypts What does the 3rd pharyngeal pouch give rise to? Inferior parathyroid gland and thymus What does the 4th pharyngeal pouch give rise to? Superior parathyroid gland, parafollicular cells of the thyroid What pouch is CN 5 derived from? What pouch is CN 7 derived from? What pouch is CN 9 derived from? What pouch is CN 10 derived from? What does the foregut give rise to? mouth, pharynx, lower respiratory tract, esophagus, stomach, liver, pancreas, duodenum What does the midgut give rise to? small intestine, appendix, cecum, ascending colon, transverse colon What does the hindgut give rise to? distal 1/3rd of the transverse colon, descending colon, sigmoid colon, rectum What are the 4 types of support cells in the CNS? What do they do? - Astrocyte - Blood brain barrier, repair, many functions - Oligodendrocyte - makes myelin in CNS - Microglia - macrophage of CNS (engulf foreign and dead particles) - Ependymal - makes up choroid plexus (line the ventricles) What type of cell forms myelin sheath around cells in the PNS? From where are the extensors formed? hypomere of myotome What muscles do the epimere of the myotome form? Those innervated by the dorsal ramus of the spinal nerves (back muscles) What are the three parts of the mesoderm? What do they form? - Dermatome --> Dermis - Sclerotome --> Bone (vertebral column) - Myotome --> muscle What controls the skeletal muscles? What controls the visceral organs? What is hypomere? What is the Falx cerebri? crescent shaped extension of the dura mater, projects between the two cerebral hemispheres What sinus runs along the Falx Cerebri? superior sagittal sinus What are the 4 lobes of the brain? What are their main functions? - Frontal - motor - Parietal - evaluation of emotion - Temporal - hearing and smell - Occipital - vision What is the main function of the prefrontal area? What three sulcus surround and divide the motor and sensory parts of the brain? Name them from ant. to post. Precentral sulcus, central sulcus of rolando and postcentral sulcus What is the primary function of the precentral gyrus? What is the main function of the postcentral gyrus? What is another name for it? - Anterior parietal lobe What is Wernickes area? Where is it? - Sensory speech - Comprehension of words - Parietal lobe Where does the blood supply for the brain originate? - Anterior - Internal carotid artery - Posterior - Vertebral artery What is the lowest level that the vertebral that the vertebral artery passes through the transverse foramen? What artery feeds broca's area? Middle cerebral artery What arteries are in the circle of Willis? Posterior Cerebral, Posterior Communicating, Internal Carotid, Anterior Cerebral, Anterior Communicating What is the circle of Willis? where the anterior circulation of the brain meets the posterior circulation What are the branches of the internal carotid artery? Anterior cerebral artery, opthalmic artery and middle cerebral artery Where is the anterior communicating artery? Between the right and left anterior cerebral arteries What are the branches of the middle cerebral artery? Posterior communicating artery and anterior choroidal artery What are the branches of the vertebral artery? Posterior Inferior cerebellar artery, Anterior and posterior spinal arteries, basilar artery, posterior meningeal artery What are the branches of the basilar artery? - 10 medullary arteries including Anterior inferior cerebellar artery, labyrinthine artery, pontine arteries and superior cerebellar artery - Also Posterior cerebral arteries Where do Berry aneurysms occur? Usually the circle of Willis Where does the middle cerebral artery supply? Lateral surface of the cortex Where does the anterior cerebral artery supply? Most of the medial surface of the neocortex Where does the posterior cerebral artery supply? What is the tentorum cerebelli? What sinus runs in the tentorum cerebelli? - Dura extension separating the cerebellum from the occipital lobe - Transverse sinus What veins empty into the External jugular vein? Posterior auricular vein and retromandibular vein What veins empty into the straight sinus? Inferior sagittal and great vein of Galen (great cerebral vein) What veins empty into the Confluence of the sinuses? Superior sagittal sinus, occipital sinus, straight sinus Where does blood flow from the confluence of the sinuses? to the transverse sinus then the sigmoid sinus Where does blood go from the sup. and inf. petrosal sinuses? - sigmoid sinus --> internal jugular vein --> subclavian vein - "internal jugular vein drains the brain What are the three types of fibers in the cerebrum and what do they do? - Association fibers - connect regions of the same hemisphere - Commissural fibers - connect the right and left cerebral hemispheres - Projection fibers - send information to other parts of the brain and spinal cord What lobe is the precentral gyrus in? What special cells does it have? What are the functions of this gyrus? - Betz cells in 4th layer - Voluntary motor, origin of corticospinal tract What lobe is the postcentral gyrus in? What are the functions of this gyrus? What areas is it? - Parietal (anterior) - Primary somesthetic (sensory) area, receives fibers from the thalamus What lobe is the prefrontal gyrus in? What are the functions of this gyrus? What areas is it? - Social Interaction What lobe is the Broca's area in? What are the functions of this gyrus? Where is it? What would a lesion here cause? - Motor speech - Left area 44 (interior frontal gyrus) - Motor aphasia What lobe is the Transverse temporal gyrus in? What are the functions of this gyrus? What lobe is the Angular gyrus in? What lobe is the uncus in? What are the functions of the uncus? - "I smell a skuncus in the uncus" What lobe is the Calcarine sulcus in? What are the functions of it? - Vision (along with visual cortex) What pathway brings information into the brain from the body? What pathway brings info. from the spinal cord/brain to the body? What part of the face covers the largest area of the sensory part of the neocortex? What is the main function of the cerebellum? unconscious coordination of muscle movements Name the four cerebellar nuclei from medial to lateral. - Dentate (the largest and most lateral) - "Fat Guy's Eat Doughnuts" What are the three layers of the cerebellum? What are the three lobes of the cerebellum and their function? - Flocculonodular - equilibrium - Anterior - proprioception (unconscious, spinocerebellar tract) - Posterior - fine motor skills What are the three different types of fibers that enter the cerebellum and what is their function? - Superior cerebellar peduncle - connects the cerebellum and cerebrum - Pontocerebellar fibers (middle cerebellar peduncle) - connects the cerebellum and the pons - Infereior cerebellar peduncle (climbing fibers) - come from the inferior olivary nucleus of the medulla - "Climb the olive tree" Name the 12 cranial nerves. - 1. Olfactory - 2. Optic - 3. Oculomotor - 4. Trochlear - 5. Trigeminal - 6. Abducens - 7. Facial - 8. Vestibulocochlear - 9. Glossopharyngeal - 10. Vagus - 11. Accessory nerve (cranial root and spinal root) - 12. Hypoglossal nerve Where is the decussation of the pyramids? What is another name for the corticospinal tract? What is the lateral geniculate body involved in? What is the medial geniculate body involved in? What is the superior colliculus involved in? What cranial nerve comes off dorsal to the brainstem? Trochlear (CN IV) What pathway does sight follow? Rods and cones (layer 2) --> bipolar cells --> ganglion cells of the retina --> Optic nerve --> Optic chiasm --> optic tract --> lateral geniculate body --> Superior colliculus (visual motor functions) and calcarine cortex of occipital lobe (via the geniculocalcarine tract) What pathway does hearing follow? - Spiral organ of corti --> CN VIII (cochlear nucleus) --> Lateral lemniscus (through trapezoid body) --> Inferior colliculus --> medial geniculate body --> temporal lobe of the cortex - LIME = Lateral, Inferior, Medial, Ear Where are the Superior and inferior colliculi located? What is the obex? The fold at the bottom of the 4th ventricle Where are the geniculate bodies located? Lateral to the colliculi in the dorsal mesencephalon What is the main function of the pons? To relay fibers going to the cerebellum (pontocerebellar fibers via the Middle cerebellar peduncle) Where is the pons located? - Superior to the medulla oblongata - Ventral to the cerebellum - Inferior to the midbrain Where is the medulla oblongata located? Caudal to the pons What two important structures does the medulla oblongata contain? Olives and the pyramids What is the main function of the basal ganglia? Background muscle tone What 4 structures are in the basal ganglia? - Lentiform nucleus - Caudate nucleus - Substantia Nigra What makes up the lentiform nucleus? Where do fibers from the globus pallidus terminate? What does a lesion of the basal ganglia cause? Parkinson's disease (Paralysis agitans) What does a lesion in the basal ganglia result in? No dopamine in substantia nigra What are the symptoms of Parkinson's? - Resting tremor - Festinating gate - Toe walk - Mask face What is another name for the anterior pituitary? What is it derived from? - Rathke's Pouch (oral ectoderm) What is the link between the CNS and the Adenohypophysis? Hypophyseal Portal system (blood) What is another name for the Posterior pituitary? What type of tissue is it? - nerve tissue Where are oxytocin and ADH (Vasopressin) formed? Where are they released? - Formed in hypothalamus - Released by posterior pituitary What is the thalamus? The major sensory integration center, it recives all senses except smell prior to the cortex Sensory fibers ascend through the thalamus to where? the sensory cortex via the Internal capsule What part of the thalamus recieves input from the cerebellum? What part of the thalamus is a synaptic region for ascending spinal sensory pathways? What part of the thalamus projects to sensory areas of the parietal and temporal lobes? What are the main functions of the thalamus? Temperature regulation, thirst, hunger, defensive reactions What hormones does the hypothalamus produce? GHRH, GHIH (somatostatin), CRH, TRH, GnRH (LHRH), PRH, PIH What does GHRH do? Stimulates the anterior pituitary to release growth hormone which stimulates the liver to produce somatomedians What does GHIH do? Decrease the production of GH What does CRH do? Stimulates the anterior pituitary to release ACTH which stimulates the adrenal gland to produce Glucocorticoids, mineralcorticoids and androgens What does TRH do? Stimulates the anterior pituitary to release TSH which stimulates the follicular cells of the thyroid to produce thyroxine What does GnRH (LHRH) do? - Stimulates the anterior pituitary to release FSH and LH - FSH in females stimulates the ovaries to produce estrogen - FSH in males stimulates the production of sperm - LH in females stimulates the production of progesterone and estrogen and stimulates the development of the ovum - LH in males stimulates the production of testosterone What does PRH do? Stimulates the anterior pituitary to release Prolactin which stimulate the breast to produce milk (oxytocin stimulates the release of milk) What does PIH do? Decreases the production of Prolactin What effect does osmolarity and Na+ have on the paraventricular and supraoptic nuclei? - High osmolarity will stimulate the paraventricular and supraoptic nuclei - High Na+ will only stimulate the paraventricular nucleus - Both release ADH (vasopressin) Which cranial nerves are parasympathetic? CN III, VII, IX, X The vagus nerve supplies parasympathetic to how much of the body? Where does CN I exit the skull? Ethmoid bone (cribiriform plate) Where does CN II exit the skull? What CN constricts the pupils? Where does the trigeminal nerve exit the skull? - Opthalmic division (I) - Superior orbital fissure - Maxillary division (II) - Foramen rotundum - Mandibular division (III) - Foramen ovale What cranial nerves exit through the superior orbital fissure? III, IV, V1, VI What is the function of CN V? General nose sensation, Senosry to face, Motor to muscles of mastication What is the function of CN VII? Taste to ant. 2/3 tongue, muscles of fascial expression What CN's exit the skull through the internal auditory meatus? What CN's exit through the jugular foramen? IX, X, XI What is the function of CN IX? Stylopharyngeus muscle (motor), taste to post. 1/3 of tongue What is the function of CN XI? SCM, trapezius motor Where does CN XII exit the skull? What is the function of CN XII? Motor to the tongue Which CN's are sensory only? I, II, VIII Which CN's are motor only? III, IV, VI, XI, XII Which CN's are both motor and sensory? V, VII, IX, X What CN is the greater petrosal/intermediate nerve associated with? What is the chorda tympani? Branch of CN 7 which carries taste Pathway of CN VII. - Internal acoustic meatus --> lacrimal gland, stapedius, taste (ant. 2/3), submaxillary and submandibular glands - --> Stylomastoid foramen --> facial muscles What CN innervates the tounge muscles? CN XII innervates all but palatoglossus which is innervated by CN X What nerve innervates the Styloglossus? What does this muscle do? - CN XII - Retract and elevate tongue What nerve innervates the Genioglossus? What does this muscle do? What muscle closes the mouth? What muscle opens the mouth? - Medial (internal) pterygoid closes - Lateral (external) pterygoid opens What are the muscles of the TMJ and what CN innervates them? - Buccinator (VII), Internal Pterygoid (V), Temporalis (V), External Pterygoid (V), Masseter (V) What part of the neuron conducts impulses toward the cell body? What part of the neuron conducts impulses away from the cell body? What is a nucleus? A group of neuron cell bodies in the CNS What is a ganglion? A group of cell bodies in the PNS What is the function of unipolar cells? Sensory, cell bodies in DRG What is the function of bipolar cells? What is the function of multipolar cells? Most neurons, motor and interneurons What type of fibers are big and myelinated? A Alpha fibers What type of fibers are small and unmyelinated? A Delta and C fibers What are the 4 main types of sensory receptors? Pain, temperature, touch, proprioception What are pain receptors? Nociceptors, free nerve endings, non-encapsulated What are the two types of temperature receptors? Krause (cold) and Ruffini (hot) What are the 4 types of touch receptors? - Merkel discs (non-encapsulated) - Meissner corpuscles - Pacinian corpuscles (pressure) - Peritrichial nerve endings What are the two main proprioception receptors? - Muscle spindles (stretch --> triggers muscle to contract) - Golgi tendon organs (protective, stretch --> triggers muscle to relax) What are the two enlargements of the spinal cord? Cervical enlargement (1-3cm) and lumbar enlargement (1-2cm) What is the conus medullaris? The end of the cord (at L1-2 level) What is the lumbar cistern? - Subarachnoid space from L2 to S2 - Contains the Cauda Equina (ends at S2) List the meninges from inside to outside. Pia, arachnoid, dura (PAD) What is the Leptomeninx? - Pia and arachnoid - "Leprachaun peed on a spider" What is Pachymeninx? What are the three major projects of dura mater into brain fissure? - Falx cerebri - between the cerebral hemispheres - Tentorium cerebelli - between the cerebellum and cerebrum - Falx cerebelli - between the cerebellar hemispheres Where are arachnoid granulations? In the subarachnoid space where CSF is located What are the two many functions of the pia mater? - Denticulate ligaments which hold the spinal cord in place (tooth-like projections) - Filum terminale interna at a the end of the spinal cord is pia only What are the three names for the posterior plate of a spinal cord? Dorsal, alar, sensory plate What are the three names for the anterior plate of the spinal cord? Basal, Ventral, Motor plate What do the dorsal primary rami innervate? Postural muscles, back What is the DRG? Dorsal root ganglion - cell bodies of somatosensory neurons What plexuses come from the ventral primary rami? cervical, brachial, lumbar, sacral What is the sulcus limitans? separation between the sensory (alar) and the motor (basal) plate What is the mantle layer of the spinal cord? What is the marginal layer of the spinal cord? What is gray matter made of? lamina and nuclei What lamina are in the posterior horn? 1 to 6 What is lamina 2? What lamina are in the anterior horn? 8 and 9 Where are the cell bodies of the lower motor neurons? Anterior horn of the spinal cord Where do neurons to axial muscle originate? What does lamina 7 contain? Lateral horn or intermediaolateral cell column Where do sympathetic fibers originate? lateral horn of T1 to L2 Where do parasympathetic fibers originate? Cranial nerves 3, 7, 9, 10 and S2,S3,S4 The sympathetic and parasympathetic are part of what nervous system? What does the anterolateral tract contain? Spinothalamic and spinoreticular tracts Where is the lateral corticospinal tract? Dorsolateral part of spinal cord Where is the Ventral corticospinal tract? Medial, ventral part of spinal cord What makes up the dorsal columns? Fasiculus Gracilis (legs) and Fasciculus cuneatus (arms) What is the pathway for the dorsal columns? What is another name for it? - Upper limb unconscious proprioception: DRG --> Fasiculus --> nuclei --> Accessory cuneate nucleus --> inf. cerebellar peduncle --> cerebellum - Lower limb unconscious proprioception: DRG --> Dorsal nucleus of clark (lamina VII, C8 to L3) --> Dorsal spinocerebellar tract --> cerebellum - All others: DRG --> Fasiculus --> nuclei --> Medial lemniscus --> Thalamus (VPL) --> postcentral gyrus (somatosensory) - Medial leminiscal system What parts of dorsal column/ML pathway are ipsilateral? Contralateral? - Lower limb unconscious proprioception, whole limbs is ipsilateral (crosses over twice) - Lower limb unconscious proprioception, individual muscles and all others are contralateral What is the function of the dorsal columns? Conscious and unconscous proprioception, vibration, 2 point discrimination What is the function of the posterior spinocerebellar tract? Unconscious proprioception to the cerebellum from lower limbs What is the function of the anterior spinocerebellar? stretch from spindle cells of lower limbs What is the spinocerebellar pathway? DRG --> nucleus of clark C8 to L3 --> inferior cerebellar peduncle --> cerebrum What causes Fredeicks ataxia? damage to the spinocerebellar pathway What does the lateral spinothalamic pathway carry? pain and temperature What does the anterior spinothalamic pathway carry? Light touch and pressure What is the spinothalamic pathway? First order neuron to DRG (2nd order synapse) --> crosses over --> 2nd order neuron to medulla then midbrain then thalamus (3rd order synapse) --> 3rd order neuron to somesthetic area of cortex (post central gyrus) Where is the 2nd order synapse for the spinothalamic tract? Lamina 4,5,6 (nucleus proprius) What type of fibers are the anterior spinothalamic 1st order neurons? A beta fibers What type of fibers are the lateral spinothalamic 1st order neurons? A delta and C fibers What does the spinotectal pathway carry? Tactile stimulation causing visual reflexes What is the spinotectal pathway? DRG --> crosses over --> tectum (superior colliculus) What does the spinoreticular pathway carry? What is the spinoreticular pathway? What is another name for it? - Same as spinothalamic except it also synapses in the reticular formation and hypothalamus as well as the thalamus - Paleospinothalmic tract What are the pyramidal tracts? Lateral and anterior corticospinal tracts What is the function of the corticospinal tract? Conscious, voluntary motor movements form the cerebral cortex of Giant cells (betz cells) especially fine movements of the hands What will a lesion in the corticospinal tract cause? What is the lateral corticospinal pathway? Motor cortex --> contralateral pyramid (lower medulla - dexussation of pyramids) --> spinal cord anterior horn What is the anterior corticospinal pathway? Motor cortex --> ipsilateral medulla --> contralateral spinal cord anterior horn (crosses at level of muscle) What % of the corticospinal tract is lateral? anterior? What descending tracts are extra pyramidal tracts? Rubrospinal, Reticulospinal, Vestibulospinal, Tectospinal What does the rubrospinal tract do? Facilitates flexors, inhibits extensors, coordinates movements Where does the rubrospinal tract originate? Red nucleus in tegmentum (floor of the midbrain) What is unique about the rubrospinal tract? Some fibers can cross at termination What does the reticulospinal tract do? Control of respiration and heartbeat, faciliate muscles, inhibit antagonists (Involuntary) - unconscious focusing while maintaining balance Where does the reticulospinal tract orginate? What does the vestibulospinal tract do? - Posture and balance - Head and eye coordinated movement - Extension of erector spinae - Truns head toward sight and sound Where does the vestibulospinal tract originate? What does the tectospinal tract do? Postrual reflexes to sight and sound Where does the tectospinal pathway originate? tectum of midbrain (superior colliculus) What is an upper motor neuron lesion? Lesion that involves any central neuron conveying impulses to the anterior horn (from brain to anterior horn but does NOT include the anterior horn cell) What is a lower motor neuron lesion? Involves the anterior horn cell, the anterior roots of the peripheral nerve What are the symptoms of an UMNL? Spastic paralysis, increased muscle tone, hyperreflexia, pathological reflexes What are the symptoms of an LMNL? Flaccid paralysis, decreased muscle tone, hyporeflexia, NO pathological reflexes What is a preganglionic neuron? - Visceral efferent neuron whose cell body is in the brain or spinal cord - Terminates at an autonomic ganglion where it synapses with a postganglionic neuron What is a postganlionic neuron? - Lies entirely outside the CNS - Cell body is located in an autonomic ganglion - Unmyelinated axon, terminates in a visceral effector What preganglionic neuron does not end on an autonomic ganglion? Sympathetic innervation to the adrenal medulla (releases Norepinephrine and Epinephrine) What does cholinergic mean? That the neuron uses acetylcholine as a neurotransmitter What does adrenergic mean? That a neuron uses epinephrine and norepinephrine as a neurotransmitter What nerves in the autonomic nervous system are cholinergic? - All parasympathetic - Preganglionic sympathetic - Postganglionic sympathetic to sweat glands, erector pilae and blood vessels What nerves in the autonomic nervous system are adrenergic? Sympathetic postganglionic to smooth muscle, cardiac muscle and glands What is the parasympathetic nervous system? - Wine and Dine system - rest and digest What is the pathway of CN 3 parasympathetic fibers? - Preganglionic to ciliary ganglion - Postganglionic to Intrinsic eye muscles (sphincter pupillae - consticts, ciliary muscle) What is the pathway of CN 7 parasympathetic fibers? - Preganglionic to Submandibular/Pterygopalatine ganglion - Postganglionic to lacrimal and salivary glands (tears) What is the pathway of CN 9 parasympathetic fibers? - Preganglionic to otic ganglion - Postganglionic to parotid gland (stensons duct - opposite second molar) What is the pathway of CN 10 parasympathetic fibers? - Preganglionic to myenteric and auerbach plexus - Postganglionic to smooth muscle and glands of the thoracoabdominal cavity up to the left colic/splenic flexure What is the pathway of S2,S3,S4 parasympathetic fibers? - Preganglionic to pelvic plexus via pelvic splachnics of hypogastric plexus - Postganglionic to colon below the splenic flexure (descending colon, sigmoid, rectum), sex organs, kidney, bladder What are the main functions of the 4 parasympathetic cranial nerves? - CN 3 - pupil and ciliary body constriction - CN 7 - tearing and salivation - CN 9 - salivation - CN 10 - vagus What nerves are needed to maintain an erection? - Parasympathetic (S2, S3, S4) - "S2,3,4, keep your penis off the floor How does the parasympathetic system effect the body? (6) - Constricts eye pupil - Increases secretions of lacrimal gland (tears) - Increases saliva in all salivary glands - Bronchoconstriction of larynx, trachea, bronchii, lungs - Decreases heart rate - Increases digestive activity What is the Sympathetic nervous system? - "fight or flight" system Fate of sympathetic fibers. (3) - Fibers go to paravertebral sympathetic chains (pre --> post here) then out to organs - Fibers leave the sympathetic chain without synapsing and leave via splanchnic nerves to synapse at a prevertebral splanchnic ganglion - Innervate the adrenal medulla What innervation do blood vessels have? - Arteries and veins have sympathetic only, capillaries have no innervation - Blood vessels have NO parasympathetic innervation What are the splanchnic nerves and what levels do they come from? - T5-T9 --> greater splanchnic nerve - T10-T11 --> lesser splanchnic nerve - T12 --> least splanchnic nerve - L1-L3 --> Lumbar splanchnic nerve What are the 4 splanchnic ganglion and what organs do they go to? - Greater: celiac --> thoracoabdominal cavity through the small intestine - Lesser: superior mesenteric --> ascending colon - Least: superior mesenteric --> ascending colon - Lumbar: inferior mesenteric --> descending colon, sigmoid, rectum, sex organs, bladder What does the superior cervical ganglion do? - Dilates eye - Stimulates tear production - Squeezes out saliva from glands then cuts off blood supply to salivary glands --> dry mouth What does the malleus attach to? What does the incus attach to? malleus and stapes What does the stapes attach to? What are the main parts of the inner ear? Cochlea and semicircular canals and vestibule The auditory/eustachian tube is part of what? What are the boundaries of the middle ear? Tympanic membrane to the oval and round window of the inner ear Name the ear bones from tympanic membrane to oval window. - Malleus, Incus, Stapes - "can't MIS the order of the bones" What does the posterior wall of the middle ear communicate with? Mastoid air cells What does the anterior wall of the middle ear open to? What is the vestibule of the ear? The central part of the bony labyrinth, contains the utricle and saccule What are the semicicular canals? Canals (3) which open into the posterior part of the vestibule. Each canal has a swelling at one end called the christa ampullaris What is the cochlea? resembles a snail shell, opens into the anterior part of the vestibule, it consists of a central pillar called the modiolus which is perforated by the cochlear nerve What does the basilar membrane of the ear do? What does it line? - seperates the cochlea into two canals: the scala vestibuli (above) and the scala tympani (below) - spiral organ of corti What is the bony labyrinth? cavities within the bone, they each contain fluid called perilymph (between membranous and bony labyrinth) What is the membranous labyrinth? - Within the boney, consists of utricle, saccule and three semicircular ducts (inside the canals) and the duct of the cochlea - filled with endolymph How is sound heard? - Vibration of the ossicles in the middle ear push the oval window and cause waves of in the fluid of the cochlea - These waves move the hair cells on the spiral organ of corti and stimulate nerve impulases via CN VIII to the cochlea nucleus What is the purpose of the saccule? - static equilibrium and linear acceleration - lying down or horizontal What is the purpose of the utricle? - Static equilibrium and linear acceleration - standing or vertical What is the macula? thickening on the saccule and utricle walls What are sterocilia and kinocilium? - Ends of hair cells in the macula which extend through an otolithic membrane - When you move your head the otolithic membrane slides and stimulates the hair cells which are connected to CN VIII What do semicircular canals detect? - rotational movement in three planes (rotational, circular and angular) - dynamic equilibrium - Anterior and posterior canal - vertical - Lateral canal - horizontal What is the ampulla? - Dilated portion of each duct, contains crista (hair cells covered with gel called cupula) - As you rotate your head hair cells move in the gel and stimulate the vestibular part of CN VIII What is chemoreceptor sense? smell (chemicals stimulate the sense) Where does smell go? - NOT through the thalamus - Olfactory bulb, limbic system Where is the emotional part of smell? Uncus of the anterior parahippocampus Pathway of smell Fila olfactoria (Olfactory neurosensory neuron, CN I) --> cribiform plate of ethmoid bone --> olfactory bulb (mitral cells) --> uncus What are the three nasal meatuses and what drains into them? - Superior (olfactory epithelium) - posterior ethmoidal air cells - Middle - Maxillary and frontal - Inferior - Nasolacrimal What are the nasal meatuses and concha? - Nasal meatuses - spaces found between the nasal concha - Superior and middle concha - on ethmoid bone - Inferior concha - own process (not part of ethmoid bone) What is the olfactory bulb an extension of? What are the functional cells of smell? Mitral and tufted cells What type of neurons project through the cribiform plate? What type of cells make up the olfactory bulb and tract? What are the two types of interneurons? - periglomerular cells - spread the impulse around - granule cells - have only dendrites (no axons) (dendrodendritic synapses) Layers of the eye out to inner - sclera (continuation of the conjunctiva) - choroid (vascular layer) - Uvea (choroid, ciliary body and iris - all pigmented) - Retina (rods = black and white vision, peripheral vision; cones = color vision, concentrated in the macula) What happens when ciliary muscles contract? suspensory ligaments relax and the lens becomes convex (spherical) What are the three chambers of the eye? - Anterior - cornea to iris (CIA) - Posterior - Iris to lens - Vitreous - lens to retina What does the posterior chamber contain? Ciliary body which produces aqueous humor What is the flow of aqueous humor? What will a blockage cause? Posterior chamber to anterior chamber and out Canal of Schlemm to venous system (blockage at Canal of Schlemm --> Glaucoma) Where are cones the most concentrated? Macula lutea and fovea centralis (center of the macula) What is the optic disc? Blind spot which allows the passage of vessels and optic nerve out of eye, the retina develops from here What artery supplies the eye? What reaction does the pupillary light reflex cause? - CN II sees the light - Parasympathetic from Edinger Westphal nucleus send signals through CN III to constrict the pupil - CN III causes the reaction How will Argyll-Robertson pupil present? Pupil accomodates but does not react What type of cells is the retina made of? Extraocular muscles are supplied by? SO4 LR6, the rest are CN III What occurs in accomodation? - Convergence of eyes - Constriction of pupil - Contraction of the lens Which CN opens the eye? Which closes? - CN III opens - CN VII closes What are the four types of partial vision loss? What part of the vision is lost in each? - Anopsia of one eye - vision is lost completely in one eye and remains normal in the other - Right nasal hemianopsia - vision is lost in the nasal half of the vision field in right eye - Bitemporal hemianopsia - vision lost in the temporal half of the vision field in both eyes - Left homonymous hemianopsia - Loss of the left half of the vision field in both eyes Where does vision from the superior retina go? Parietal lobe optic radiation to the area above the calcarine fissure Where does vision from the inferior retina go? Temporal lob optic radiation to the area below the calcarine fissure Where does vision from the left half of each retina go? To the left side of the brain Where do objects in right visual field go? Left side of the brain Damage to the optic chiasm will cause vision loss where? In the temporal fields of vision (nasal part of retina) Damage to the left optic nerve will cause vision loss where? Damage to the left optic tract will cause vision loss where? Right visual field in both eyes Damage to the left temporal lobe optic radiation will cause vision loss where? Superior half of right visual field in both eyes What does the endoneurium do? surrounds individual nerve fibers What does the perineurium do? Surrounds small bundles or fascicles of fibers What does epineurium do? Surrounds the entire nerve What nerves innervate the diaphragm? C3,4,5 (phrenic nerve) - "C3,4,5 keeps the diaphragm alive" What nerves innervate the SCM and trapezius? CN XI and C1-5 What nerves are in the cervical plexus? Where cutaneous (sensory) nerves does the cervical plexus supply? - Small/lesser occipital nerve from C2 - Great auricular nerve - Transverse cervical (anterior cutaneous) nerve - Supraclavicular nerve (top of shoulders) What nerves make up the brachial plexus? Ventral rami of C5-T1 Where does the axillary nerve come from? What does it supply? - Off of the posterior cord of the brachial plexus - Motor: Teres Minor, Deltoid - Sensory: Anterior shoulder Where does the musculocutaneous nerve come from? What does it supply? - Off of the lateral cord, accompanies the radial artery - Motor: Coracobrachialis, biceps, brachialis (forearm flexors) - Sensory: Anterior forearm Where does the Median nerve come from? What does it supply? - Off medial and lateral cord, accompanies brachial artery - Motor: Wrist flexors and pronators, thenar muscles - Sensory: First 3.5 digits and palm What does a lesion of the median nerve cause? Ulnar nerve? Radial nerve? - Median --> Ape hand - Ulnar --> Claw hand - Radial --> wrist Drop - "Dr. Cu Ma" Where does the Ulnar nerve come from? What does it supply? - Off medial cord - Motor: Hand interossei and lumbricals, hypothenar muscles, thumb adduction - Sensory: Pinky and 1/2 of ring finger Where does the Radial nerve come from? What does it supply? - Off posterior cord - Largest branch - Motor: Forearm and wrist extensors and supinators, tumb extension - Sensory: Posterior arm and hand What is another name for the long thoracic nerve? What does it supply? - External respiratory nerve of bell - Motor: serratus anterior What does the suprascapular nerve supply? Supra and infra spinatus What does the medial and lateral pectoral supply? - Medial --> Pec major and minor - Lateral --> Pec major only Where does the Thoracodorsal nerve come from? What does it supply? - Off posterior cord - Also called Middle subscapularis - Motor: Latissimus dorsi Summary of which nerves come from which cord. - PART: Posterior --> Axillary, Radial, Thoracodorsal - MUM: Middle --> Ulnar, 1/2 of Median - LMM: Lateral --> 1/2 of Median, Musculocutaneous Summary of thumb movements. - Radial --> Extension - Ulnar --> Adduction - Median --> Flexion (opposition) What nerves are part of the lumbar plexus? T12 to L4 What supplies the ilioinguinal nerve? What supplies the genitofemoral nerve? What supplies the Lateral femoral cutaneous nerve? - "She's 23 and too CUTe for me" What supplies the Femoral nerve? What supplies the obturator nerve? What nerves make up the sacral plexus? L4 to S3 What nerves are in the lumbosacral trunk? What supplies the superior gluteal nerve? What supplies the Inferior gluteal nerve? L5 to S2 What supplies the posterior femoral cutaneous nerve? What makes up the sciatic nerve? Common peroneal and tibial nerves, L4 to S3 What bones are in the axial skeleton? Skull, vertebral column, ribs, sternum and hyoid Which skull bones are paired? Temporal, parietal, maxilla, nasal, lacrimal, inferior concha, zygomatic Which skull bones are not paired? Frontal, occipital, mandible, sphenoid, ethmoid (includes cribiform plate and superior and middle concha) What bones are part of the eye? Zygomatic, frontal, lacrimal, ethmoid, maxilla, sphenoid What type of joint are sutures? What does the coronal suture separate? frontal from parietal bones What does the sagittal suture separate? 2 parietal bones What does the squamous suture separate? temporal from parietal bones What does the lambdoidal suture separate? occipital from parietal What does the internasal suture separate? 2 nasal bones What does the intermaxillary suture separate? 2 maxillary bones What does the frontonasal suture separate? Frontal and nasal bones What does the occipitomastoid suture separate? occiput from the mastoid What does the parietomastoid suture separate? parietal from the mastoid What is the bregma? Intersection of the coronal and sagittal sutures What is the glabella? flattened triangular area of the forehead What is the nasion? Intersection of frontal and nasal sutures What is the pterion? Intersection of the frontal, sphenoid, temporal and parietal bones What is the asterion? Intersection of squamous and lambdoid sutures and the mastoid sutures What is lambda? Intersection of lambdoid and sagittal sutures How many vertebrae are there? - 24 moveable (7 cervical, 12 thoracic, 5 lumbar) - Sacrum, coccyx How many spinal and cranial nerves are there? Where do they exit? - 31 pairs of spinal nerves - 12 cranial nerves - Cervical nerves 1-7 exit above the corresponding veretebra, all others exit below, Cervical nerve 8 exits between C7 and T1 What part of the spine is made up of IVDs? Which vertebra are typical? C3-6, T2-8, L1-4 Typical cervical vertebra. - Oval body - Triangular spinal canal - Joint plane coronal 45 degrees - Superior facet direction is posterosuperior, slightly medial Typical thoracic vertebra. - heart-shaped body - oval spinal canal - joint plane coronal 65 degrees - Superior facet direction is posterosuperior, slightly lateral Typical lumbar vertebra. - kidney-shaped body - triangular spinal canal - Joint plane is sagittal 90 degrees - Superior facet direction is posteromedial Which cervicals have a bifurcated Spinous? What are joints of luschka? Where are they found? - Uncovertebral joints - C2/3 to C6/7 Which joints of the spine have the most mechanoreceptors? Zygaphophyseal joints of cervicals Which TP has the carotid tubercle? Which vertebra have transverse foramen? C1-7 but vertebral artery does not always pass through C7 foramen, usually starts at C6 What forms the IVF? - Posterior border: articular pillars (facet) - Roof and floor: pedicles (inferior vertebral notch of the vertebra above and the superior vertebral notch of the vertebra below) - Anterior: uncinate processes (body and IVD) Which veretebra are atypical? C1, C2, C7, T1, T9-12, L5, sacrum, coccyx (11 total) Where does the longus coli muscle insert? anterior tubercle of atlas Where is the groove for the suboccipital nerve and vertebral artery? Superior aspect of the posterior arch of atlas What is the fovea denatalis? groove on the posterior surface of the anterior arch, dens fits in it What is tropism? Where is it most common? assymetrical facets, most common at L5/S1 (one coronal, one sagittal) What is sacralization? lumbarization? - sacralization - incomplete separation of L5 and sacrum - lumbarization - S1 separates from sacrum What are the major parts of the sacrum? What are they analogous to? - Median crest - SPs - Intermediate crest - articular pillars - Lateral crest - TPs - Sacral promentory - anterior portion of the most superior aspect - Cornu - horn Which ribs are typical? what do they articulate with? - Ribs 2-9 - superior demifacet of corresponding vertebra - inferior demifacet of vertebra above - full costal facet on the TP articulates with rib tubercle Which ribs are true ribs? Which ribs are false ribs? Which ribs are floating? 11 and 12 Which ribs articulate with one rib? 1, 10, 11, 12 (all have a 1 in them) What type of joints do the ribs participate in? - costovertebral and costotransverse - gliding - costochondral - cartilaginous What is the pars interarticularis? region of bone between the superior articular process and the inferior articular process What is a good rule of thumb for determining how superficial a back muslce is? Loner muscles are more superficial What are the actions of rhomboideus major and minor? - major - adduct scapula - minor - retracts scapula What are the three erector spinae (layer IV) muscles? - Iliocostalis - most lateral, attaches to ribs, no attachement to vertebra - Spinalis - most medial - "I Love Spinal!" What muscles are in layer 1 of the back muscles? Trapezius, latissimus dorsi What muscles are in layer 2 of back muscles? Rhomboideus major and minor, levator scapulae What muscles are in layer III of the back muscles? Splenius capitis and cervicis, serratus posterior superior and inferior What muslces are in layer V of the back muscles? All other back muscles not mentioned for layers I to IV (transverse spinal, sub-occipital, anterior vertebral, lateral vertebral) Where does the rectus capitis anterior originate? lateral mass of occiput Where does the psoas major insert? Where does the iliacus originate and insert? - origin - iliac crest and sacrum - insertion - psoas major What layer is the levator costorum in? layer 5 (lateral vertebral) What nerve supplies the suboccipital triangle? Posterior primary divison of C1 What runs through the suboccipital triangle? vertebral artery and 1st cervical nerve (suboccipital) What is another name for the lumbar triangle? What are its boundaries? - Lateral: external oblique - Medial: latissimus dorsi - Inferior: iliac crest - Floor: Internal oblique What are the boundaries of the triangle of auscultation? - Medial: traps - Inferior: lats - Lateral: medial scapula At what level is the PSIS? Iliac crest? - PSIS - S2 - Iliac crest - L4 What are the 9 common ligaments of the spine? IVD, ALL (anterior longitudinal), PLL (posterior longitudinal), Capsular, Interspinous, Supraspinous, Ligamentum nuchae, Intertransverse, Ligamentum flavum What is the IVD made of? Where do its parts originate from? What is its function? - fibrocartilage (symphysis joint) - Annulus fibrosis - from sclerotome - nucleus pulposis - from notochord - resists flexion and extension and all motions of the spine What is the tectoral membrane a continuation of? What is the function of the PLL? Where is it located? - prevent the disc from herniating into the vertebral canal - posterior to the body, on the anterior part of the vertebral canal Where is the interspinous ligmament? between the spinous processes Where is the supraspinous ligament? What does it become? - lays over the spinous processes - above C7 it is the nuchal ligament What si the function of the intertransverse ligament? resist lateral flexion (runs TP to TP) Hypertrophy of what ligament will cause canal stenosis? ligamentum flavum (yellow ligament) Where is the yellow ligament? What is its function? What is unique about it? - runs from lamina to lamina in posterior portion of vertebral canal (it is inside the canal) - strengthens the medial aspect of the zygapophyseal joint and resists flexion - only elastic ligament in the body Where does the tectoral membrane attach? C2 to foramen magnum, superior continuation of PLL What is another name for the alar ligament? Where does it attach? check ligament, attaches the occipital condyles to dens, limits rotation of axis What is another name for the apical ligament? Where does it attach? suspensory ligament, attaches the dens to the foramen magnum What is the purpose of the transverse ligament? Holds the odontoid (dens) to atlas in the fovea dentalis What membrane has the greatest tendency to ossify? posterior atlantooccipital membrane What is the denticulate ligament? extension of pia What does the sacrotuberous ligament do? Where does it attach? resists flexion, attaches the sacrum to the ischial tuberosities What does the iliolumbar ligament do? becomes taut during hip extension Where does the inguinal ligament attach? What is it formed by? ASIS to pubic tubercle, formed by the aponeurosis of the external oblique abdominal muscle What is the cremasteric muscle formed by? aponeurosis fo the internal abdominal oblique muscle What ligaments make up the cruciate ligament? Transverse, superior longitudinal and the inferior longitudinal What passes around the sacrospinous ligament? The pudental nerve and vessels pass around this ligament to the ischiorectal fossa What structures are in the greater sciatic foramen? - Piriformis muscle - Superior and inferior gluteal vessels - Superior and inferior gluteal nerves - Internal pudendal vessels - Pudendal nerve - Sciatic nerve - Posterior femoral cutaneous nerve - Nerves to the obturator internus and quadratus femoris muscles What structures are in the lesser sciatic foramen? - Tendon of the obturator internus - Nerve to the obturator internus - Internal pudental vessels - Pudendal nerve What would you like to do? Home > Flashcards > Print Preview	2	19	0	0	0	2	0.682903	2	13,233
ICD-10-CM Code R06.2 Billable CodeBillable codes are sufficient justification for admission to an acute care hospital when used a principal diagnosis. R06.2 is a billable ICD code used to specify a diagnosis of wheezing. A 'billable code' is detailed enough to be used to specify a medical diagnosis. The ICD code R062 is used to code Wheeze A wheeze (formally called "sibilant rhonchi" in medical terminology) is a continuous, coarse, whistling sound produced in the respiratory airways during breathing. For wheezes to occur, some part of the respiratory tree must be narrowed or obstructed, or airflow velocity within the respiratory tree must be heightened. Wheezing is commonly experienced by persons with a lung disease; the most common cause of recurrent wheezing is asthma attacks, though it can also be a symptom of lung cancer. \|ICD 9 Code:\|\|786.07\| Coding Notes for R06.2 Info for medical coders on how to properly use this ICD-10 code Code Type-1 Excludes: Type-1 ExcludesType-1 Excludes mean the conditions excluded are mutually exclusive and should never be coded together. Excludes 1 means "do not code here." - Asthma - instead, use code J45.- - DRG Group #204 - Respiratory signs and symptoms. Related Concepts SNOMET-CT - Wheezing stridor (finding) ICD-10-CM Alphabetical Index References for 'R06.2 - Wheezing' The ICD-10-CM Alphabetical Index links the below-listed medical terms to the ICD code R06.2. Click on any term below to browse the alphabetical index. Equivalent ICD-9 Code GENERAL EQUIVALENCE MAPPINGS (GEM) This is the official exact match mapping between ICD9 and ICD10, as provided by the General Equivalency mapping crosswalk. This means that in all cases where the ICD9 code 786.07 was previously used, R06.2 is the appropriate modern ICD10 code.	4	2	0	0	0	12	0.562866	12	466
March 17, 2003 In an abrupt break from the legislative history of the Americans with Disabilities Act (ADA or the Act), the position of the executive agencies responsible for enforcing the ADA, and the prior rulings of eight of the nine federal courts of appeal that had addressed the issue, the Supreme Court decided that mitigating measures should be considered in determining whether an individual has a disability under the ADA. This policy brief examines the function and types of ameliorating measures, the prior near-consensus that such measures should not be interjected into the determination of disability, the Supreme Court's decisions on the issue, and the repercussions of the Court's position. The Role of Mitigating Measures The relationship between the concepts of impairment and disability is not linear, because the interaction between physical and mental impairments and the physical and social environment is not simple and uniform. A prior policy brief in theRighting the ADA series discussed the social model of disability in the ADA as opposed to the traditional medical model of disability . In accordance with the social model, the ADA was concerned primarily with addressing discrimination and not with differentiating one group of people as having disabilities and others as not; it was intended to focus more on the attitudes and perceptions of those accused of discrimination than on the precise physical or mental characteristics of the persons allegedly discriminated against. As applied by the courts, however, the ADA definition has all too often been construed as a narrow gateway to ADA protection that often depends upon technical distinctions about what constitutes a disability under the Act. In this context, the starting point in determining disability is the identification of some trait or condition of a person, typically a diminishment, absence, or unconventional version of some physical or mental capability or attribute that most other people usually have. In the terminology of the ADA, such conditions are referred to as "impairments." Where an impairment occurs, various techniques may be brought to bear to eliminate, reduce, compensate for, or sidestep its effects. The most dramatic type of corrective measure is one which "cures" or removes the impairment. Sometimes, medications can successfully treat an ailment and a person recovers fully without any ongoing symptoms or need for subsequent medication or treatment. In some situations, surgery or other medical procedures may remove the cause of an impairment and thereby eliminate the impairment. Some types of conditions may disappear over time, on rare occasions spontaneously, or as a result of various kinds of therapeutic regimens, lifestyle changes, and other factors. In circumstances where an impairment has been fully eradicated and no restrictions or need for treatment persist, the person no longer has an impairment and is not eligible for protection under the branch of the ADA definition that applies to actual disabilities. Such a person, however, may still be able to claim ADA protection if she or he is subjected to discrimination because of the previous impairment ("a record of" impairment) or because of a misperception of ongoing impairment ("being regarded as having" an impairment). In many situations, however, a physical or mental impairment cannot be totally eliminated, but may be susceptible to various kinds of measures to control it, reduce it, compensate for its effects, or otherwise ameliorate the impact of the impairment and enable the person to function more effectively or comfortably. Such measures, which can include medications, techniques, and devices, have been called "mitigating measures." The extent of the impact of mitigating measures varies greatly from person to person, from impairment to impairment (and according to the degree of severity and the scope of the impairment), and according to the nature of the measure used. Medications, for example, can reduce or regulate the effects of various conditions, including epilepsy, diabetes, some psychiatric disabilities, HIV infection, high blood pressure, and many others. Various kinds of surgical interventions can sometimes enhance the function of people with some types of physical impairments. Wheelchairs, braces, walkers, crutches, prosthetic devices, canes, and other devices can be used to assist the functioning of people with various kinds of impairments of the arms, legs, and spine. Hearing aids, sign language, the ability to comprehend verbal speech visually (speechreading), and other devices and techniques may prove helpful to various individuals with various degrees of hearing impairments. Eyeglasses, magnifying devices, white canes, mastery of braille, and other measures may be useful for some individuals with visual impairments. Some people with severe speech impairments may use an electronic or manual speech board to communicate. Dietary restrictions can ameliorate the effects of some impairments. The mitigating measures mentioned here are merely examples of a whole gamut of measures that may be used by particular individuals to manage their impairments. Mitigating measures can be thought of as adjustments made to an individual's person or personal environment to minimize limitations that might result from impairments, as opposed to modifications of the external environment that may also be necessary. In its Toward Independence report in which it first called for the enactment of an ADA, NCD quoted from a United Nation's report as follows: Despite everything we can do, or hope to do, to assist each physically or mentally disabled person achieve his or her maximum potential in life, our efforts will not succeed until we have found the way to remove the obstacles to this goal directed by human society-the physical barriers we have created in public buildings, housing, transportation, houses of worship, centers of social life, and other community facilities-the social barriers we have evolved and accepted against those who vary more than a certain degree from what we have been conditioned to regard as normal. More people are forced into limited lives and made to suffer by these man-made obstacles than by any specific physical or mental disability. (Report of the United Nations Expert Group Meeting on Barrier-Free Design, 25 International Rehabilitation Review 3 (1975), quoted in Toward Independence (1986) at p. 1.) Consistent with this perspective, the ADA requires covered entities to take certain steps to remove obstacles to people with disabilities. These requirements include certain obligations to remove architectural, transportation, and communication barriers; to provide auxiliary aids and services; and to make reasonable accommodations in the workplace. These obligations relate to enhancing access to the services, programs, jobs, facilities, and opportunities of covered entities. The "mitigating measures" discussed in this policy brief, however, are more intimately associated with the particular person, and may benefit the individual in various settings. The Equal Employment Opportunity Commission (EEOC), for example, has distinguished between an adjustment or modification that "specifically assists the individual in performing the duties of a particular job"-which an employer may be required to provide as a reasonable accommodation-and one that "assists the individual throughout his or her daily activities, on and off the job"-which would be considered a "personal item" that an employer would generally not be required to provide (29 C.F.R. appendix to part 1630 (commentary on §1630.9)). As examples of these "personal item[s]," the EEOC listed "a prosthetic limb, wheelchair, or eyeglasses." The line between personal and nonpersonal items is not always a bright one, as the EEOC admitted when it added that eyeglasses could be a reasonable accommodation if a person with a visual impairment needed specially designed glasses to do a particular job. The Legal Position on Mitigating Measures Prior to the Supreme Court Weighing In Before the Supreme Court upset the applecart, all the relevant authorities were nearly unanimous in the view that mitigating measures should not be considered in deciding whether a person has a disability under the ADA. Even before the ADA was enacted, the committee reports on the pending legislation declared clearly that mitigating measures should not be factored in. The three ADA Committee Reports that addressed the issue all concurred that mitigating measures are not to be taken into account when determining whether an individual has a disability.1 The House Education and Labor Committee Report elaborated with the following examples: For example, a person who is hard of hearing is substantially limited in the major life activity of hearing, even though the loss may be corrected through the use of a hearing aid. Likewise, persons with impairments, such as epilepsy or diabetes, which substantially limit a major life activity are covered under the first prong of the definition of disability, even if the effects of the impairment are controlled by medication. (H.R. Rep. No. 101-485, pt. II at 52 (1990)) During floor debates regarding the ADA's coverage of psychiatric conditions, Senator Harkin, the original sponsor of the Senate Bill, made a point of noting that persons with schizophrenia, manic-depressive illness, and other mental health conditions whose conditions were controlled by medications would be able to pursue ADA claims (101 Cong. Rec. S19864 (1989) (statement of Sen. Harkin)). After the ADA was passed, both the Department of Justice (DOJ) and the Equal Employment Opportunity Commission (EEOC), the key federal agencies directed to issue regulations implementing the nondiscrimination provisions of the Act embraced the notion that mitigating measures should be excluded from the determination of disability. Regulatory commentary issued in appendices to DOJ's ADA Title II (state and local government entities) and Title III (public accommodations) regulations both contain the identical statement that "disability should be assessed without regard to the availability of mitigating measures" (28 C.F.R. § 35.104, app. A.; 28 C.F.R. § 36.104, app. B). Likewise, in the Interpretive Guidance accompanying its ADA Title I (employment) regulation, the EEOC declared that the existence of an impairment and whether an impairment substantially limits a major life activity are to be determined "without regard to mitigating measures such as medicines or assistive or prosthetic devices" (29 C.F.R. appendix to part 1630) (commentary on §§ 1630.2(h) & 1630.2(j)). Based upon the ADA committee reports, the EEOC cited the following as examples of determining impairment without regard to mitigating measures: For example, an individual with epilepsy would be considered to have a disability even if the symptoms of the disorder were completely controlled by medication. Similarly an individual with hearing loss would be considered to have an impairment even if the condition were correctable through the use of a hearing aid. (Id. (commentary on § 1630.2(h))) As examples of how impairments can be substantially limiting regardless of mitigating measures, the EEOC included the following examples, again derived from the ADA committee reports: An individual who uses artificial legs would ... be substantially limited in the major life activity of walking because the individual is unable to walk without the aid of prosthetic devices. Similarly, a diabetic who without insulin would lapse into a coma would be substantially limited because the individual cannot perform major life activities without the aid of medication. (Id. (commentary on § 1630.2(j))) The EEOC reiterated its stance on mitigating measures in its Guidance on Psychiatric Disabilities and the Americans with Disabilities Act (59 Daily Lab. Rep. E-1, p. 6 (1977)): The ADA legislative history unequivocally states that the extent to which an impairment limits performance of a major life activity is assessed without regard to mitigating measures, including medications. Thus, an individual who is taking medication for a mental impairment has an ADA disability if there is evidence that the mental impairment, when left untreated, substantially limits a major life activity. Building upon the consistent position of the regulatory agencies on the mitigating measures issue, plus the "unequivocal" legislative history cited by the EEOC, eight of the nine federal courts of appeals to address the issue had ruled that the ADA definition of "disability" should be applied without regard to ameliorative measures. This included the First, Second, Third, Fifth, Seventh, Eighth, Ninth, and Eleventh Circuit Courts of Appeals.2 Only the Tenth Circuit had ruled that mitigating measures should be considered, in the very case in which the Supreme Court first took up the issue.3 Accordingly, the legal landscape was highly one-sided in favor of the view that mitigating measures should be disregarded in determining whether an individual has a disability under the ADA. The Supreme Court's Decisions on Mitigating Measures In Sutton v. United Airlines, 527 U.S. 471 (1999), the Supreme Court rejected the overwhelming consensus of prior authority and ruled that corrective and mitigating measures must be considered in determining whether an individual has a disability under the ADA. The Court held that "the approach adopted by the agency guidelines-that persons are to be evaluated in their hypothetical uncorrected state-is an impermissible interpretation of the ADA." Id. at 482. The mitigating measure at issue in the Sutton case was corrective lenses (eyeglasses and contact lenses). In Murphy v. United Parcel Service, 527 U.S. 516, 521 (1999), the Court applied the same analysis to medication used to treat an otherwise disabling condition. In Albertson's, Inc. v. Kirkingburg, 527 U.S. 555, 565 (1999), the Court went even further and declared that mitigating measures encompass not only artificial aids, such as medications and devices, but also measures undertaken, whether consciously or not, with the body's own systems, including subconscious mechanisms for compensating and coping with visual impairments. The factual backgrounds and full holdings in the Sutton, Murphy, and Kirkingburg decisions are summarized in the NCD paper Supreme Court Decisions Interpreting the Americans with Disabilities Act (ADA) found at/newsroom/publications/2002/supremecourt_ada.htm. The Web site of the Judge David L. Bazelon Center for Mental Health Law has an insightful paper, The Supreme Court's 1999 ADA Decisions by Jennifer Mathis, that also provides a summary of the three decisions and presents some advocacy strategies for avoiding some negative effects of the decisions; it is found at http://www.webcom.com/bazelon/sct99ada.html The upshot of these rulings is starkly apparent, however: the Supreme Court drastically narrowed the class of persons protected by the ADA by excluding those whose impairments are successfully addressed by mitigating measures. The only concessions the Court has made with regard to mitigating measures are its recognition in the Sutton opinion that a person who makes use of a corrective device may still have a disability anyway if the device does not correct the condition sufficiently to prevent a substantial limitation on a major life activity;4 and its acknowledgment in the Murphy decision that people who take medication for their medical conditions may nonetheless qualify as having a disability due to limitations that persist despite the medication or due to the negative side effects of the medication.5 The Repercussions of the Court's Position on Mitigating Measures As a result of the Court's rulings in the Sutton, Murphy, and Kirkingburg cases, individuals who are currently functioning well due to mitigating measures such as medications or prosthetic devices are not protected as individuals with disabilities under the ADA. The lower courts have applied this unfortunate legal doctrine in a variety of circumstances, dismissing ADA claims because plaintiffs have not demonstrated the existence of a disability, without reaching the issue of alleged discriminatory conduct. Among the claims dismissed by the lower courts have been those of: . a machine operator with epilepsy whose medication reduced her seizures to approximately one or two per week;6 . a pharmacist with diabetes who controlled his condition with insulin injections and a controlled diet;7 . an administrative assistant with diabetes who controlled her condition to some degree by daily blood sugar tests and daily injections of insulin;8 . a forklift operator with depression controlled by medication;9 . a nurse with focal onset epilepsy controlled by medication;10 . a convenience store employee with a heart condition controlled by medication;11 . a bus driver with hypertension controlled by medication;12 . a police officer with depression controlled by counseling and medication;13 . a company president with myelodsysplastic syndrome, a form of blood cancer, whose condition was treated by chemotherapy;14 . a correctional officer, whose asthma was treated with medication but still resulted in numerous emergency room visits and absences;15 and . a county corrections officer with asthma, requiring daily medication, twice weekly injections, use of inhaler, and occasional hospitalization.16 In another case, a federal district court ruled that a stocker with epilepsy who, even with medication, experienced weekly seizures, and who, as a result of the side effects of his medication, experienced decreased cognitive function and memory problems, was nonetheless not substantially limited under the ADA.17 Recognizing the striking change in the law brought about by the Supreme Court's mitigating measures decisions, the court observed that, prior to Sutton, "a person suffering from epilepsy would receive nearly automatic ADA protection." In many of these cases, the plaintiffs were not hired, or were fired, specifically because of their impairments. In others, they were denied accommodations they had requested in order to enable them to perform their jobs or to control their conditions. In the case of the pharmacist with diabetes, for example, all he was asking of his employer was a half-hour off for lunch so that he could administer his medications and eat his lunch uninterrupted to avoid hypoglycemic episodes.18 In response, the employer allegedly refused his request and then terminated him. Because the Court of Appeals for the Eighth Circuit found that the employee was not substantially limited in any major life activities when the effects of insulin and a controlled diet were considered, it ruled that he was not protected by the ADA; it never reached the issues of the reasonable accommodation he sought, nor of his firing. This result is typical of such cases-because they are dismissed on the coverage issue, the question of whether discrimination actually occurred is never addressed. It also typifies the contradictory power given to employers by such a construction of the ADA. On the one hand, the employer can consider the underlying condition, despite mitigating measures, to be sufficiently serious to justify terminating or refusing to hire the individual. On the other hand, the employer can simultaneously contend that, because of the mitigating measures, the individual's condition is not sufficiently disabling to qualify for protection under the ADA. Another example of this contradiction occurred in the case of Spades v. City of Walnut Ridge,19 in which a police officer with depression attempted suicide. Later, after he had received successful professional treatment for his condition, he sought to return to his job. The police department decided that his condition was too debilitating to permit him to return to duty, but was able to argue successfully that his depression was not sufficiently limiting to constitute a disability because it was controlled by counseling and medication. Another troubling aspect of the lower courts' application of the mitigating measures analysis is the arbitrariness of their assessments of how much mitigation is necessary to render a condition not substantially limiting. Many of the individuals whose situations are included in the list of examples above have had quite substantial limitations even after treatment and medication. Vanessa Turpin, the machine operator with epilepsy, for instance, was taking medication and being treated by a neurologist, but continued to experience seizures about once or twice a week, some nocturnal and some in the daytime. The Court of Appeals for the Fourth Circuit described the ongoing seizures as follows: The nocturnal seizures were characterized by shaking, kicking, salivating, and at least on one occasion, bedwetting. After having these seizures, Turpin would feel tired in the morning, as if she did not sleep at all. Turpin typically was unaware that she was having seizures, and sometimes would wake up with bruises on her arms and legs. The daytime seizures were milder in nature. Over the time period at issue in this appeal, four or five seizures happened during work itself. Turpin could feel the seizure about to start, and would sit elsewhere until the episode passed. The seizures normally lasted a couple of minutes. During these seizures, Turpin began shaking, her face took on a blank expression, and she became unaware of and unresponsive to her surroundings. . . . These seizures also sometimes caused Turpin to suffer memory loss.20 The memory losses would occasionally cause Turpin to forget to take her medication, or to forget where she was going in her car. Most people would presumably consider Ms. Turpin's seizures and their effects to be substantial problems, but the Fourth Circuit ruled that she was not a person with a disability within the meaning of the ADA, and thus was not entitled to a reasonable accommodation (she sought to be allowed to work the daytime shift). The court concluded that when considered in her mitigated state (while taking medication), Turpin was not substantially limited in any major life activity, including the major life activities of sleeping, thinking, and caring for one's self. It is impossible to know what the outer limits will be of courts' application of the concept that mitigating measures can render a person otherwise eligible for protection under the ADA ineligible for such protection. A debate between the Justices in their opinions in the Sutton case suggests, however, that such an approach will be extremely far-reaching. In his dissenting opinion in Sutton, Justice Stevens pointed out that the majority's analysis would logically lead to exclusion from ADA protection of some people who wear prostheses to replace missing limbs21. He argued that some "individuals who have lost one or more limbs" are able "[w]ith the aid of prostheses, coupled with courageous determination and physical therapy," to "perform all of their major life activities just as efficiently as an average couch potato."22 In Justice Stevens's view, "when an employer refuses to hire the individual `because of' his prosthesis, and the prosthesis in no way affects his ability to do the job, that employer has unquestionably discriminated against the individual in violation of the Act." Yet the majority's approach suggests that such individuals might not be protected by the ADA at all. The majority could provide only a partial response to Justice Stevens's argument: The use of a corrective device does not, by itself, relieve one's disability. Rather, one has a disability under subsection (A) [of the ADA definition of disability] if, notwithstanding the use of a corrective device, that individual is substantially limited in a major life activity. For example, individuals who use prosthetic limbs or wheelchairs may be mobile and capable of functioning in society but still be disabled because of a substantial limitation on their ability to walk or run.... The use or nonuse of a corrective device does not determine whether an individual is disabled; that determination depends on whether the limitations an individual with an impairment actually faces are in fact substantially limiting.23 As one commentator has noted, the majority's response does not really answer Justice Stevens's criticism: The majority's analysis is something of a "non-denial denial." The Court does not quite prove Justice Stevens is wrong. It merely shows that he is not necessarily or inevitably right.... The Court relies on individualized, case-by-case, person-by-person inquiry guided by the phrase "substantially limits".... [It] all but admits that in some cases, some individuals without limbs, but using a prosthesis, might not be disabled within the meaning of the Act.24 Another commentator agreed that, under the Court's analysis, some people missing limbs or parts of limbs would not be protected by the ADA: "[f]or example, neither the late Terry Fox, who for 144 days ran a marathon (26 miles) a day across Canada on an artificial leg and inspired many other amputees to take up running, nor Heather Mills, who runs half-marathons, snowboards, skis and skates using a prosthesis for half of a leg, would be disabled under the ADA."25 Some lower courts have expanded upon the Supreme Court's analysis of mitigating measures by ruling that it applies not only to people whose conditions have actually been mitigated, but also those whose impairments could be mitigated. In one case, for example, a hospital employee with severe asthma refused to take steroidal medication prescribed by her physician because she feared the adverse effects of the medication on her pituitary tumor. The court ruled that because her asthma could probably have been mitigated by medication, she was not substantially limited in the major life activities of breathing or working, and therefore could not bring suit under the ADA.26 Commentators have called such analysis "a perverse stretch of Sutton,"27 but other courts have reached similar conclusions that if an impairment could theoretically be controlled by medication-even if in fact it has not been-the person with the condition is not substantially limited and therefore not entitled to protection under the ADA.28 Although such individuals may be experiencing substantial limitations in their major life activities, these courts have taken the view that, because they have not availed themselves of medication or other corrective devices, they are not entitled to the ADA's protections. In making its rulings on mitigating measures, the Supreme Court put into practice an approach it would later make explicit in its decision in Toyota Motor Manufacturing, Kentucky, Inc. v. Williams-that the ADA's definition of "disability" should "be interpreted strictly to create a demanding standard for qualifying as disabled ...." (122 S.Ct. at 691). In this light, theSutton, Murphy, and Kirkingburg decisions were effective vehicles for the Court to make technical distinctions to exclude classes of potential ADA claimants. If, on the other hand, one approaches the Court's rulings on mitigating measures from the ADA's stated objective of providing a "comprehensive" remedy to discrimination on the basis of disability, as announced in the purposes section and long title of the Act,29 quite a different perspective emerges. To the extent that mitigating measures are successful in reducing the negative effects of an individual's condition to a manageable level, the Supreme Court's stance on mitigating measures deprives the individual of the right to maintain an ADA action to challenge acts of disability discrimination she or he has encountered, because such a person is not eligible for the ADA's protection. This means an employer or other covered entity may discriminate with impunity against such individuals in various flagrant and less flagrant ways. Taking the example of epilepsy to illustrate this result, epilepsy was mentioned frequently in committee reports and floor debates on the ADA. The committee reports expressly included epilepsy in a list of examples of impairments.30 There is no doubt that Congress intended to prohibit unjustified discrimination based on epilepsy. Accordingly, the Department of Justice's ADA regulations listed epilepsy as a covered impairment, as had Section 504 regulations before them.31 The ADA regulatory commentary of the EEOC and the DOJ specifically declared that an individual with epilepsy would remain within the coverage of the ADA even if the effects of the condition were controlled by medication.32 And as one federal court had accurately observed, prior to Sutton, "a person suffering from epilepsy would receive nearly automatic ADA protection."33 The situation changed markedly, however, with the Supreme Court's mitigating measures decisions. To the extent that a covered entity can successfully demonstrate (after extensive, intrusive discovery into the details of the person's condition) that an individual's epilepsy is effectively controlled by medication, the individual cannot challenge the discriminatory actions of the covered entity. This is true even if the employer or other covered entity has an express policy against the hiring of persons with epilepsy, puts up signs that say "epileptics not welcome here," inaccurately assumes that all persons with epilepsy are inherently unsafe, or has the irrational belief that epilepsy is contagious. The unfairness or irrationality of the covered entity's actions and motivations, including false stereotypes, fears, assumptions, and other forms of prejudice, cannot be challenged by a person whose condition is mitigated. If persons with epilepsy whose conditions are controlled by medication are the only individuals having epilepsy who happen to encounter the covered entity's discrimination, the entity will be free to continue its blatantly discriminatory policies and practices. This leaves only people with epilepsy whose conditions are not controlled by medication to bring such a covered entity to task under the ADA. But if such persons' seizures are seriously debilitating and frequent, it is quite likely that they will be found not "qualified" for jobs or other opportunities, and thus denied ADA protection anyway. If, on the other hand, their unmitigated conditions are not severe or their seizures are relatively rare, there is a good chance that their conditions will be held not to be "substantially limiting." This is a prime example of the unfortunate "Catch-22"34 that ADA complainants often find themselves frustrated by: either your condition is not serious enough to constitute a disability or it is too serious for you to be qualified. The end result is that it is a rare plaintiff who is in a position to challenge even the most egregious and outrageous discrimination involving a condition that can be mitigated. The Supreme Court's rulings on mitigating measures, then, almost completely undercut the congressional intent that the ADA prohibit discrimination against persons with epilepsy. And epilepsy is merely discussed here as an illustrative example of the consequences of the mitigating measures rulings. The same principles apply to diabetes, various psychiatric disabilities, hypertension, arthritis, and numerous other conditions that, for some individuals, can be controlled by medication. Moreover, the same problems arise with conditions for which techniques and devices other than medication provide an avenue for mitigation. Thus, a company that discriminates against people who use hearing aids will be insulated from challenge by people for whom the hearing aids are effective in restoring functional hearing ability. In the end, the Supreme Court's position on mitigating measures ignores the rationale that led courts, regulatory agencies, and Congress to take a contrary position-that unless you disregard mitigating measures in determining eligibility for ADA protection, you shield much discrimination on the basis of disability from effective challenge. The result of the Sutton, Murphy, and Kirkingburg decisions is to turn the ADA's terminology into an instrument for slashing out large groups of potential beneficiaries instead of for forcefully eliminating instances of the pervasive unfair and unnecessary discrimination that the law sought to prohibit. This policy brief was written for the National Council on Disability by Professor Robert L. Burgdorf Jr. of the University of the District of Columbia, David A. Clarke School of Law. Some of the material about lower court decisions was derived from an earlier paper in the Righting the ADA Series written by Sharon Perley Masling, Director of Legal Services, National Association of Protection and Advocacy Systems. That paper is found on the NCD Web site atwww.ncd.gov/newsroom/publications/2003/decisionsimpact.htm. 1 See S. Rep. No. 101-116, at 23 (1989) ("whether a person has a disability should be assessed without regard to the availability of mitigating measures"); H.R. Rep. No. 101-485, pt. II at 52 (1990) ("Whether a person has a disability should be assessed without regard to the availability of mitigating measures"); H.R. Rep. No. 101-485, pt. III at 28 (1990) ("The impairment should be assessed without considering whether mitigating measures ... would result in a less-than-substantial limitation"). 2 Arnold v. United Parcel Service, Inc., 136 F.3d 854, 859-866 (1st Cir. 1998); Bartlett v. New York State Bd. of Law Examiners, 156 F.3d 321, 329 (2d Cir. 1998); Matczak v. Frankford Candy & Chocolate Co., 136 F.3d 933, 937-938 (3d Cir. 1997); Washington v. HCA Health Servs. of Texas, 152 F.3d 464, 470-471 (5th Cir. 1998); Baert v. Euclid Beverage, Ltd., 149 F.3d 626, 629-630 (7th Cir. 1998); Doane v. Omaha, 115 F.3d 624, 627 (8th Cir. 1997); Holihan v. Lucky Stores, Inc., 87 F.3d 362, 366 (9th Cir. 1996); Harris v. H & W Contracting Co., 102 F.3d 516, 520-521 (11th Cir. 1996). 3 Sutton v. United Air Lines, Inc., 130 F.3d 893 (10th 1997). Some judges on the Sixth Circuit had expressed some doubt about the majority rule. Gilday v. Mecosta County, 124 F.3d 760, 766-768 (1997) (Kennedy, J., concurring in part and dissenting in part); id., at 768 (Guy, J., concurring in part and dissenting in part). 4 Sutton v. United Airlines, 527 U.S. 471, 488 (1999). 5 Murphy v. United Parcel Service, 527 U.S. 516, 521 (1999). 6 EEOC v. Sara Lee, 237 F.3d 349 (4th Cir. 2001). 7 Orr v. Wal-Mart Stores, Inc., 297 F.3d 720 (8th Cir. 2002). 8 Nordwall v. Sears, Roebuck & Co., 46 Fed. App. 364, 2002 WL 31027956 (7th Cir. 2002) (unpublished). 9 Boerst v. General Mills, 2002 WL 59637 (6th Cir. 2002) (unpublished). 10 Chenoweth v. Hillsborough Co., 250 F.3d 1328 (11th Cir. 2001), cert denied, 534 U.S. 1131 (2002). 11 Taylor v. Nimock's Oil Co., 214 F.3d 957 (8th Cir. 2000). 12 Hill v. Kansas Area Transp. Auth., 181 F.3d 891 (8th Cir. 1999). 13 Spades v. City of Walnut Ridge, 186 F.3d 897, 900 (8th Cir. 1999). 14 EEOC v. R.J. Gallagher Co., 181 F.3d 645 (5th Cir. 1999) (ruled plaintiff not substantially limited, but remanded to the lower court on issues of coverage under "record of" or "regarded as" prongs). 15 Muller v. Costello, 187 F.3d 298, 314 (2d Cir. 1999). 16 Saunders v. Baltimore Co., 163 F. Supp. 2d 564 (D. Md. 2001). 17 Todd v. Academy Corp., 57 F. Supp. 2d 448, 453-54 (S.D. Tex. 1999). 18 Orr v. Wal-Mart Stores, Inc., 297 F.3d 720 (8th Cir. 2002). 19 186 F.3d 897, 900 (8th Cir. 1999). 20 EEOC v. Sara Lee, 237 F.3d 349, 351 (4th Cir. 2001). 21 Sutton v. United Airlines, 527 U.S. 471, 498 (1999) (Stevens, J., dissenting). 22 Id. at 497. 23 Id. at 488. 24 Harry F. Tepker, Jr., "Writing the Law of Work on Nero's Pillars: The 1998-99 Term of the U.S. Supreme Court," 15 The Labor Lawyer 181, 191 (1999). 25 Vicki J. Limas, "Of One-Legged Marathoners and Legally Blind Pilots: Disabling the ADA on a Case-by-Case Basis," 35Tulsa Law Journal 505, 532 (2000) (footnotes omitted). 26 Tangires v. Johns Hopkins Hospital, 79 F. Supp. 2d 587 (D. Md. 2000), aff'd by unpublished opinion, 230 F.3d 1354 (4th Cir. 2000). 27 Jeffrey A. Van Detta & Dan R. Gallipeau, "Judges and Juries, Why are So Many ADA Plaintiffs Losing Summary Judgment Motions, and Would They Fare Better Before a Jury?: A Response to Professor Colker," 19 Review of Litigation 505, 520 n. 36 (Summer 2000). 28 See, e.g., Hein v. All Am. Plywood Co., 232 F.3d 482, 487 (6th Cir. 2000) (truck driver with hypertension who refused to drive a delivery run since he was unable to obtain a medication refill prior to the trip not substantially limited; driver's condition should be viewed in its mitigated state since he voluntarily failed to take his medication); Rose v. Home Depot, 186 F. Supp. 2d 595, 613-614 (D. Md. 2002) ("failure to take the proper measures to gain a proper diagnosis necessary to a proper treatment plan is the legal equivalent of a refusal to avail oneself of proper treatment" because plaintiff "has effectively avoided a reasonable opportunity to achieve mitigating diagnoses and treatment"; plaintiff therefore failed to present proof that he has a disability as defined by the ADA); Hewitt v. Alcan Aluminum Corp., 185 F. Supp 2d 183 (N.D.N.Y. 2001) (fork lift truck driver with post-traumatic stress disorder (PTSD) not substantially limited where PTSD could be mitigated by medication, which truck driver voluntarily chose not to take); Spradley v. Custom Campers, Inc. 68 F. Supp. 2d 1225 (D. Kan. 1999) (maintenance worker with epilepsy and active seizures not substantially limited where probability of seizures would have been much lower if worker had taken prescribed medication). 29 42 U.S.C. § 12101(b)(1) ("to provide a clear and comprehensive national mandate for the elimination of discrimination against individuals with disabilities"); Pub. L. No. 101-336, long title, 104 Stat. 327 (1990) ("An Act to establish a clear and comprehensive prohibition of discrimination on the basis of disability"). These and other indications in the ADA and in the definition of disability that Congress intended the Act to receive an expansive interpretation are examined in another paper in the Righting the ADA series: /newsroom/publications/2003/broadnarrowconstruction.htm. 30 S. Rep. No. 101-116, at 22 (1989); H.R. Rep. No. 101-485, pt. 2 at 51 (1990). 31 28 C.F.R. § 35.104 (par. (1)(ii) of definition of "physical or mental impairment") (DOJ Title II regulation); 28 C.F.R. § 36.104 (par. (1)(iii) of definition of "physical or mental impairment") (DOJ Title III regulation); 45 C.F.R. pt. 84 app. A (commentary on § 84.3(j)(1)) (HHS Section 504 regulation); 42 Fed. Reg. 22,685 (1977) (original HEW Section 504 regulatory commentary); 28 C.F.R. § 41.31(b)(1) (DOJ Section 504 coordination regulation). 32 29 C.F.R. appendix to pt. 1630 (commentary on § 1630.2(h)); 28 C.F.R. preamble to pt. 35 (commentary on § 35.104, par. (1)(ii) of definition of "physical or mental impairment"); 28 C.F.R. § preamble to pt. 36 (commentary on § 36.104, par. (1)(iii) of definition of "physical or mental impairment"). 33 Todd v. Academy Corp., 57 F.Supp. 2d 448, 453-54 (S.D. Tex. 1999). 34 Numerous authorities have noted this "Catch-22" dilemna. See, e.g., National Council on the Handicapped, Toward Independence, Appendix A-25 (1986); Doe v. Region 13 Mental Hlth.-Mental Retard. Comm'n, 704 F.2d 1402 (5th Cir. 1983); Tudyman v. United Airlines, 608 F. Supp. 739, 744 (C.D. Cal. 1984); Richard A. Bales, "Once Is Enough: Evaluating When a Person Is Substantially Limited in her Ability to Work," 11 Hofstra Labor Law Journal 203, 239 (1993); Robert L. Burgdorf Jr., "The Americans with Disabilities Act: Analysis and Implications of a Second-Generation Civil Rights Statute," 26 Harvard Civil Rights-Civil Liberties Law Review 413, 448 (1991); Jonathan Brown, "Defining Disability in 2001: A Lower Court Odyssey," 23 Whittier Law Review 355 (2001); Arlene B. Mayerson and Kristan S. Mayer, "Defining Disability After Sutton: Where Do We Go From Here?," 27 Human Rights 13 (2000). See also Williams v. Avnet, Inc., 910 F.Supp. 1124, 1131 (E.D.N.C. 1995) (referring to necessity of plaintiff proving that she is substantially limited in working and simultaneously qualified as "two conflicting elements" of establishing that one is included in "the ADA's protected class").	2	109	2	0	0	0	0.58477	2	8,547
In human–computer interaction, computer accessibility (also known as accessible computing) refers to the accessibility of a computer system to all people, regardless of disability type or severity of impairment. The term "accessibility" is most often used in reference to specialized hardware or software, or a combination of both, designed to enable use of a computer by a person with a disability or impairment. Specific technologies may be referred to as assistive technology. There are many disabilities or impairments that can be a barrier to effective computer use. These impairments, which can be acquired from disease, trauma, or may be congenital, include but are not limited to: - Cognitive impairments (head injury, autism, developmental disabilities), and learning disabilities, such as dyslexia, dyscalculia or ADHD. - Visual impairment such as low-vision, complete or partial blindness, and color blindness. - Hearing-related disabilities including deafness, being hard of hearing, or hyperacusis. - Motor or dexterity impairment such as paralysis, cerebral palsy, dyspraxia, carpal tunnel syndrome and repetitive strain injury. Accessibility is often abbreviated as the numeronym a11y, where the number 11 refers to the number of letters omitted. This parallels the abbreviations of internationalization and localization as i18n and l10n respectively. - 1 Special-needs assessment - 2 Considerations for specific impairments - 3 Software accessibility - 4 Open Accessibility Framework - 5 Standards and Regulations - 6 See also - 7 References - 8 External links People wishing to overcome an impairment in order to use a computer comfortably and productively may require a "special needs assessment" by an assistive technology consultant (such as an occupational therapist, a rehabilitation engineering technologist, or an educational technologist) to help them identify and configure appropriate assistive technologies to meet individual needs. Even those who are unable to leave their own home or who live far from assessment providers may be assessed (and assisted) remotely using remote desktop software and a web cam. For example, the assessor logs on to the client's computer via a broadband Internet connection, observes the users computer skills, and then remotely makes accessibility adjustments to the client's computer where necessary. Considerations for specific impairments Cognitive impairments and illiteracy The biggest challenge in computer accessibility is to make resources accessible to people with cognitive disabilities - particularly those with poor communication and reading skills. As an example, people with learning disabilities may rely on proprietary symbols and thus identify particular products via the product's symbols or icons. Unfortunately copyright laws can limit icon or symbol release to web-based programs and websites by owners who are unwilling to release them to the public. In these situations, an alternative approach for users who want to access public computer based terminals in libraries, ATMs, and information kiosks is for the user to present a token to the computer terminal, such as a smart card, that has configuration information to adjust the computer speed, text size, etcetera to their particular needs. The concept is encompassed by the CEN EN 1332-4 Identification Card Systems - Man-Machine Interface. This development of this standard has been supported in Europe by SNAPI and has been successfully incorporated into the Local Authority Smartcards Standards e-Organisation (LASSeO) specifications. Since computer interfaces often solicit visual input and provide visual feedback, another significant challenge in computer accessibility involves making software usable by people with visual impairments. For individuals with mild to medium vision impairment, it is helpful to use large fonts, high DPI displays, high-contrast themes and icons supplemented with auditory feedback, and screen magnifying software. In the case of severe vision impairment such as blindness, screen reader software that provides feedback via text to speech or a refreshable braille display is a necessary accommodation for interaction with a computer. About 8% of people suffer from some form of color-blindness. The main color combinations that might be confused by people with visual deficiency include red/green and blue/green. However, in a well-designed user interface, color will not be the primary way to distinguish between different pieces of information. Motor and dexterity impairments Some people may not be able to use a conventional input device, such as the mouse or the keyboard, therefore, it is important for software functions to be accessible using both devices. Ideally, software will use a generic input API that permits the use even of highly specialized devices unheard of at the time of software's initial development. Keyboard shortcuts and mouse gestures are ways to achieve this access, as are more specialized solutions, including on-screen software keyboards and alternate input devices (switches, joysticks and trackballs). Speech recognition technology is also a compelling and suitable alternative to conventional keyboard and mouse input as it simply requires a commonly available audio headset. The astrophysicist Stephen Hawking's use of assistive technology is an example of a person with severe motor and physical limitations who uses technology to support activities of daily living. He uses a switch, combined with special software, that allows him to control his wheelchair-mounted computer using his limited and small movement ability. This personalized system allows him to remain mobile, do research, produce his written work. Mr. Hawking also uses augmentative and alternative communication technology to speak and an environmental control device to access equipment independently. A small amount of modern research indicates that utilizing a standard computer mouse device improves fine-motor skills. While sound user interfaces have a secondary role in common desktop computing, these interfaces are usually limited to using system sounds such as feedback. Some software producers take into account people who can't hear due to hearing impairments, silence requirements or lack of sound producing software. System sounds like beeps can be substituted or supplemented with visual notifications and captioned text (akin to closed captioning). Closed captions are a very popular means of relaying information for the Deaf and hearing impaired communities. Accessibility Application Programming Interfaces (APIs) - Java Accessibility and the Java Access Bridge for Java software (being standardized as ISO/IEC TR 13066-6); - Assistive Technology Service Provider Interface (AT-SPI) on UNIX and Linux (being standardized as ISO/IEC PDTR 13066-4 ); - Microsoft Active Accessibility (MSAA) on Microsoft Windows; - IAccessible2 on Microsoft Windows, a competitor of Microsoft UI Automation also replacing MSAA by Free Standards Group (standardized as ISO/IEC 13066-3:2012); - Mac OS X Accessibility; - Microsoft UI Automation on Microsoft Windows, replacing MSAA. Accessibility features in mainstream software Accessibility software can also make input devices easier to access at the user level: - Keyboard shortcuts and MouseKeys allow the user to substitute keyboarding for mouse actions. Macro recorders can greatly extend the range and sophistication of keyboard shortcuts. - Sticky keys allows characters or commands to be typed without having to hold down a modifier key (Shift, Ctrl, Alt) while pressing a second key. Similarly, ClickLock is a Microsoft Windows feature that remembers a mouse button is down so that items can be highlighted or dragged without holding the mouse button down while scrolling. - Customization of mouse or mouse alternatives' responsiveness to movement, double-clicking, and so forth. - ToggleKeys is a feature of Microsoft Windows 95 onwards. A high sound is heard when the CAPS LOCK, SCROLL LOCK, or NUMBER LOCK key is switched on while a low sound is heard when any of those keys is switched off. - Customization of pointer appearance, such as size, color and shape. - Predictive text - Spell checkers and grammar checkers Support for learning disabilities Other approaches that may be particularly relevant to users with a learning disability include: - Cause and effect software - Switch accessible software - Hand–eye coordination skills software - Diagnostic assessment software - Mind mapping software - Study skills software - Symbol-based software - Touch typing software Enabling access to Web content for all users is the concern of the Web accessibility movement, which strives to create accessible websites via conformance to certain design principles. For example, screen readers are of limited use when reading text from websites designed without consideration to accessibility. Sometimes these limitations are due to the differences between spoken and written language and the complexity of text, but it is often caused by poor page design practices. The tendency to indicate semantic meaning using methods that are purely presentational (e.g. larger or smaller font sizes, using different font colors, embedded images, or multimedia to provide information) restricts meaningful access to some users. Therefore, designing sites in accordance with Web accessibility principles helps enable meaningful access for all users. Open Accessibility Framework The Open Accessibility Framework (OAF) provides an outline of the steps that must be in place in order for any computing platform to be considered accessible. These steps are analogous to those necessary to make a physical or built environment accessible. The OAF divides the required steps into two categories: creation and use. The “creation” steps describe the precursors and building blocks required for technology developers to create accessible applications and products. They are as follows: - Define what “accessible” means for the identified use of the platform. It must be clear what is meant by “accessible” as this will differ according to the modality and capabilities of each platform. Accessibility features may include tabbing navigation, theming, and an accessibility API. - Provide accessible stock user interface elements. Pre-built “stock” user interface elements, used by application developers and authoring tools, must be implemented to make use of the accessibility features of a platform. - Provide authoring tools that support accessibility. Application developers and content authors should be encouraged to implement tools that will improve the accessibility features of a platform. Using these tools can support accessible stock user interface elements, prompt for information required to properly implement an accessibility API, and identify accessibility evaluation and repair tools. The “use” steps describe what is necessary in the computing environment in which these accessible applications will run. They are as follows: - Provide platform supports. Computing platforms must properly implement the accessibility features that are specified in their accessibility definition. For example, the accessibility API definitions must be implemented correctly in the program code. - Provide accessible application software. Accessible applications must be available for the platform and they must support the accessibility features of the platform. This may be achieved by simply engaging the accessible stock elements and authoring tools that support accessibility. - Provide assistive technologies. Assistive technologies (e.g. screen readers, screen magnifiers, voice input, adapted keyboards) must actually be available for the platform so that the users can effectively interface with the technology. The following examples show that the OAF can be applied to different types of platforms: desktop operating systems, web applications and the mobile platform. A more complete list can be found in the Open Source Accessibility Repository by the Open Accessibility Everywhere Group (OAEG). - Accessibility APIs include the Assistive Technology Service Provider Interface and UI Automation on the desktop, WAI-ARIA in web applications, and the Blackberry Accessibility API on the Blackberry operating system. - Other APIs are keyboard access and theming in widget libraries like Java Swing for desktop applications, the jQuery UI and Fluid Infusion for Web applications, and the Lightweight User Interface Toolkit (LWUIT) for mobile applications. - Support for accessible development can be effective by using Glade (for the GTK+ toolkit), the DIAS plugin for NetBeans IDE, Xcode IDE for iOS applications. Accessibility inspection tools like Accerciser (for AT-SPI) and support for accessible authoring with the AccessODF plugin for LibreOffice and Apache OpenOffice also fit into this step. - Support for UI Automation on Microsoft Windows, support for ATK and AT-SPI in Linux GNOME, WAI-ARIA support in Firefox, and the MIDP LWUIT mobile runtime (or the MIDP LCDUI mobile runtime) that is available on mobile phones with Java are examples of APIs. - The DAISY player AMIS on the Microsoft Windows desktop and the AEGIS Contact Manager for phones with Java ME are designed for accessibility. - The GNOME Shell Magnifier and Orca on the GNOME desktop, GNOME's ATK (Accessibility Toolkit), the web-based screen reader WebAnywhere, and the alternative text-entry system Dasher for Linux, iOS and Android are examples of assistive technologies. The goal of the listed tools is to embed accessibility into various mainstream technologies. Standards and Regulations ISO 9241-171: Ergonomics of human-system interaction - Guidance on software accessibility Compiled from independent standards experts, this document is the most comprehensive and technical standard for designing accessible features for software, covering all disabilities and all aspects of software. It provides examples of two priority levels ('Required' and 'Recommended') and offers a handy checklist designed to help with recording software testing results. The only trouble is that because of its complexity and technical nature, and with upwards of 150 individual statements, ISO 9241-172 is difficult to interpret and apply. Luckily, not every statement is relevant to every situation, therefore it may be advisable to identify a subset of statements that are tailored to the particular software environment, making the use of this document much more achievable. - AccessApps - a collection of accessibility software which fits on a USB drive - Assistive Technology - Augmentative and alternative communication - Fire Vox - Game accessibility - Section 508 Amendment to the Rehabilitation Act of 1973 - Web accessibility - CEN: Personal identification, electronic signature and cards and their related systems and operations - Structure. - "Draft EN 1332-4 Identification Card Systems - Man-Machine Interface - Part 4 : Coding of user requirements for people with special needs". Tiresias.org. 2009-11-20. Retrieved 2013-07-28.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles> - LASSeO: Feasibility Studies - Final Report. August 2011. - Bohannon, John (December 19, 2013). "Click here to improve your motor skills". Science. Retrieved 23 December 2013.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles> - Oracle: Java Accessibility - Oracle: Java SE Desktop Accessibility (page containing a link to the Java Access Bridge). - ISO: ISO/IEC PRF TR 13066-6: Information technology -- Interoperability with Assistive Technology (AT) -- Part 6: Java accessibility application programming interface (API). - ISO: ISO/IEC PDTR 13066-4: Information Technology - Interoperability with Assistive Technology (AT) -- Part 4: Linux/UNIX graphical environments accessibility API. - ISO: ISO/IEC TR 13066-3:2012: Information technology -- Interoperability with assistive technology (AT) -- Part 3: IAccessible2 accessibility application programming interface (API). - Richard Hodgkinson: 7th Report on International ICT Accessibility Standards Proposed, Being Developed and Recently Published. 3 October 2008. - Richard Hodgkinson: 10th Report on International ICT Accessibility Standards Proposed, Being Developed and Recently Published. 26 June 2009. - Microsoft: Using ClickLock - Microsoft: To turn on ToggleKeys. Windows XP Professional Product Documentation. - Bates, Roger; Jones, Melanie (2003). "Using Computer Software To Develop Switch Skills". 2003 [Technology and Persons with Disabilities] Conference Proceedings. Retrieved 2007-02-08.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles> - Hawes, Paul; Blenkhorn, Paul (2002). "Bridging the Gap between Aspiration and Capability for Aphasic and Brain Injured People". 2002 [Technology and Persons with Disabilities] Conference Proceedings. Retrieved 2007-02-08.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles> - AEGIS Consortium: AEGIS OAF and high-level architecture. Accessed 2013-01-17. - AEGIS Consortium: AEGIS Architecture Definition. Accessed 2013-01-17. - Open Accessibility Everywhere Group (OAEG): Open Source Accessibility Repository. Accessed 2013-01-17. - Research in Motion (RIM): Package net.rim.device.api.ui.accessibility. BlackBerry JDE 6.0.0 API Reference. Accessed 2013-01-17. - Fluid Infusion. Accessed 2013-01-17. - Glade - A User Interface Designer. Accessed 2013-01-17. - DIAS Netbeans IDE plugin & Standalone. Accessed 2013-01-17. - Apple Inc.: Xcode 4. Accessed 2013-01-17. - AccessODF. Accessed 2013-01-17. - Microsoft Developer Network: Accessibility (.NET Framework 4.5). Accessed 2013-01-17. - Microsoft Windows Dev Center: UI Automation (Windows). Accessed 2013-01-17. - GNOME Dev Center: Introducing ATK, AT-SPI, GAIL and GTK+. Accessed 2013-01-17. - Access Mozilla. Accessed 2013-01-17. - Access Firefox: Firefox Accessibility Features. Accessed 2013-01-17. - AEGIS Consortium: LWUIT - Mobile Accessibility. Accessed 2013-01-21. - DAISY Consortium: AMIS: DAISY 2.02 & DAISY 3 Playback Software. Accessed 2013-01-17. - AEGIS Contact Manager. Accessed 2013-01-17. - WebInSight: WebAnywhere: A Screen reader on the go. Accessed 2013-01-17. - Inference Group (University of Cambridge): Mobile Dasher. Accessed 2013-01-17. - Dasher for iOS on iTunes. Accessed 2013-01-17. - Iosif Klironomos, Julio Abascal, Ilse Bierhoff: D3.1 Report with background material needed to support the SDDP-2 Meeting: An Introduction to the Key Issues Relating to Accessible User Interfaces. Accessed 2013-01-17. \|Wikimedia Commons has media related to [[commons:Lua error in Module:WikidataIB at line 506: attempt to index field 'wikibase' (a nil value).\|Lua error in Module:WikidataIB at line 506: attempt to index field 'wikibase' (a nil value).]].\| - The annual ERCIM Workshop on 'User Interfaces for All' emphasising accessibility - Better Living Through Technology - contains guides on accessibility options and information about specialist assistive hardware and software - HP Accessibility - AbilityNet - provides information on Accessibility, Assistive Technology and Remote Assessment - C4EA Consortium For E-learning Accessibility - W3C Web Accessibility Initiative (WAI) - Accessibility in the Opera web browser - Mozilla Accessibility Project - Open Office Accessibility Project - EU Project GUIDE: Multimodal user interfaces for elderly people with mild impairments	2	17	4	0	0	0	0.173507	4	4,072
Home > Flashcards > Print Preview The flashcards below were created by user on FreezingBlue Flashcards. What would you like to do? A pregnant woman in the third trimester presents with swelling of the legs and headaches. Her blood pressure is elevated and urinalysis show 4+ protein. These findings are most consistent with: The pediatrician tells the parents that their child has a greenstick facture. In layman�s terms, what is a greenstick fracture? A partial break that results in one side of the broken bone bending Is a condition in which bone resorption exceeds bone deposition A y oung boy was bitten by a wild dog and contracted rabies. He subsequently suffered from fever, headache, photophobia, and seizures. An MRI showed inflammation of the brain. He is suffering from: What condition is characterized by shuffling gait, tremors, pill-rolling, and muscular rigidity? A neural tube defect: Spina bifida (and anencephaly) Dermatologic condition caused by bacterial infection: Pelvic inflammatory disease is managed aggressively because long-term effects can include: A 21-year-old female is infected by HPV following unprotected sexual intercourse. She is now at higher risk of developing what type of cancer? A 54-year-old male was recently diagnosed with osteoarthritis. What type of symptoms is he most likely to experience? Which disease is characterized by thick, silvery, scaly, erythematous plaques surrounded by normal skin? A 50-year-old male recently underwent a liver transplant and is taking immunosuppressive drugs. He now has pain and vesicular eruptions on the trunk that follow one nerve line. He reports that he had chickenpox as a child. What is his most likely diagnosis? Herpes zoster (shingles) An 11-year-old male is newly diagnosed with type 1 diabetes mellitus. Before treatment he most like experienced: Polydipsia, polyuria, polyphagia, and weight loss Congenital hypothyroidism that is not managed is a serious concern because of the risk for: Mental retardation (and growth failure) Greaves� disease is an autoimmune disease in which there is excess ________ hormone secretion: An autoimmune disease that blocks the ACH receptors of the sarcolemma, causing extreme muscle weakness is: What virus causes infectious mononucleosis? Which of the following STDs is viral? - GENITAL HERPES Which of the following is associated with upper gastrointestinal bleeding? - ESOPHAGEAL VARICES - Colon cancer - Crohn�s disease What type of disease could result in a mechanical bowel obstruction? The cardinal sign of pyloric stenosis is: Infection with Helicobacter pylori is associated with which of the following: Peptic ulcer disease A patient presents with McBurney�s point tenderness, a high leukocyte count, fever, and vomiting. What does this patient most likely have? A 28-year-old female presents with severe chest pain and shortness of breath. She is diagnosed with pulmonary embolism, which most likely originated from the: Deep veins of the leg The most common cause of pulmonary edema is: Left heart failure (at the left ventricle) A 53-year-old male with a 20-year history of smoking is diagnosed with emphysema. He is having difficulty breathing because of: Destruction of alveolar septa A 30-year-old male prison inmate contracted tuberculosis during an outbreak. He may transmit the disease to others through: A 25-year-old female is diagnosed with urinary tract obstruction. She has not urinated for 36 hours. A renal ultrasound shows: A 60-year-old male is diagnosed with chronic renal failure. Which lab values would be most consistent with this diagnosis? Elevated plasma creatinine level Hearing loss caused by stiffening of the bones of the middle ear is called: Elisabeth Kubler-Ross� 5 stages of greif: Which defense mechanism would a person be displaying by blaming her health problems on her troubled relationship rather than admitting to depression as the cause? In young adulthood (ages 19-40), when there is a reappraisal of one�s life, which one of Erikson�s theories applies? Intimacy vs. isolation A terminally ill patient states, �I am not really sick; I am just having a bad day.� This patient is most likely in which stage of dying, according to Elisabeth Kubler-Ross? Which of the following statements about the elderly is FALSE? - SUICIDE IS RARE AMONG THE ELDERLY - Alzheimer�s disease is more common in the elderly than in young people - The elderly experience thin and saggin skin - Presbyopia is common among the elderly - Elderly men have difficulty achieving and maintaining erections Which is the most common psychiatric disorder in the elderly? - Personality disorder - Alzheimer�s disease anxiety Which of the following does Maslow say is the most basic human need that needs to be met before any others? - FOOD AND WATER Who provided the foundation for the modern study of psychology? Which of the following is NOT a part of FREUD�S structure of personality? - According to Freud, which of the following is a function of the ego? A previously toilet-trained child is hospitalized and then begins wetting the bed again. This is an example of which defense mechanism? Maslow�s Hierarchy of Human Needs is based on the concept that: There is a progression of human needs People use unconscious behaviors to protect themselves from guilt or shame. These are called: A mother gives her child expensive gifts to make up for not spending enough time with him. Which defense mechanism does this example describe? When conducting a patient history, what type of listening behaviors will be most effective? A patient in the medical office suffers from loss of memory. A technique useful in communicating with this patient is to: Direct the patient to perform one task at a time A 4-year-old is in the office for allergy testing. The BEST way to prepare the child for this procedure is to: Use role-playing to demonstrate the procedure to the child. The MA may repeat back a patient�s statements as a way to encourage open communication. Which technique is this? The MA will restate, reflect, or seek clarification of the patient�s statements to encourage effective communication. This is referred to as: A nonverbal method of displaying openness to communication would be: Leaning forward, with eyes focused on the communicator Three of the elements required for communication to occur are: Message, sender, receiver Which of the following is the best way to teach a patient how to perform a procedure themselves, such as changing a dressing? - Intnernet website - Verbal description - Video description - Video tape The relationship between an employee and employees, co-workers, and patients is influenced by a number of personal traits. Which of the following is most important? - EFFECTIVENESS IN COMMUNICATION - Empathy with others� problems Questions that can be answered with yes or no are called: Law that is based on prior rulings from a court is: HIPAA provides standards for the interchange of electronic data to protect the privacy and confidentiality of electronically stored and transmitted health information. One of the goals of HIPAA is NOT: - TO REDUCE THE USE OF COMPUTER NETWORKS IN HEALTH CARE - To increase the reliability of shared data - To reduce fraud - To accelerate processes and reduce paperwork - To improve tracking of health information Confidential medical records on the office computer. To maintain patient confidentiality, the MA should NEVER: - Share their personal computer password with co-workers - Leave the computer unsecured during lunch break or at the end of the day - Print out confidential information without monitoring the print function An effective tool to ensure patient confidentiality would be to: Provide independent verification of a fax number before faxing confidential data Which of the following actions may be performed using a patient�s implied consent? - AN ELECTROCARDIOGRAM - Donation of organs after death - A blood transfusion - Release of medical records - Gallbladder surgery A patient has had open heart surgery and is in a coma. The patient�s spouse brings suit against the physician, alleging that the patient was not informed of the possible complications from use of general anesthesia. The suit will be filed on the following basis: Malfeasance is one form of: Which of the following is NOT a felony under the law? An expressed contract is: In what instance is consent NOT required? In an emergency situation What may be found in an advance directive? Medical power of attorney The testimony provided in a sworn, pretrial setting is: The doctrine respondeat superior applies to: The responsibility of the physician for his or her actions as well as staff members The MA sees an apparent conflict between ethics and patient confidentiality in a situation not covered under the law. The MA should: Refer the conflict to the physician for his or her decision The reasonable person rule compares an action with one that would be performed by a prudent and reasonable person under similar circumstances. Failure to act in this manner would constitute: By law, the physician MUST report: - Communicable diseases - Suspected abuse Which of the following is NOT a part of the Patient Bill of Rights? - The right to privacy notices - A reasonable response from the physician when medical services are requestesd - THE RIGHT TO NEGOTIATE FEES FOR MEDICAL SERVICES RECEIVED - The right to refuse treatment under circumstances prescribed by law A minor child comes into the medical office for immunizations required by the school. The medical assistant notices bruising on the patient and suspects child abuse. The appropriate first step for the MA is to: Notify the physician privately of your concern The standard envelope size for general business correspondence is: The appointment book of a medical office is set up by crossing off all times that will not be used for patient visits. This is known as setting up a: The file that is inserted on the shelf when a medical record is in use is an: The use of electronic mail has one major disadvantage, which is that it: Is not secure The medical office has been cited for storing boxes of medical supplies in front of an emergency exit. The agency or person citing this infraction is: The local fire inspection agency The medical office will maintain referral information for the convenience of patients. This will include referral information for: - Drug and alcohol abuse counselors - Agencies providing financial aid to the needy - Legal services Certified mail is special handling for which classification of mail? The most appropriate when processing the daily mail is to: Date stamp each item Which type of insurance pays benefits when an accident or serious illness results in loss of pay? Business correspondence and postcards are mailed by: A multi-physician medical practice uses two boxes of syringes daily. With each box containing 25 syringes. How many boxes of syringes will need to be ordered each month? Is eligible for mailing up to 70 pounds Water is accidentally left on the floor of the restroom. A patient is asked to provide a urine sample and slips and falls on the wet floor. If the patient brings a lawsuit against the medical office, the insurance policy that will provide protection is: Items such as deeds and wills are valuable documents, but do not have a significant monetary value. The best way to mail this type of document would be using: The trial balance of accounts receivable is prepared: Payments for professional services by cash, check, or credit card are called: The MA can find information regarding the filing of reports and taxes from the employee�s earnings and employer�s tax contributions in the: IRS Employer�s Tax Guide The MA applies a discount to an unpaid balance on a patient account. This action is referred to as an: The following ledger entry reduces the balance owed by a patient, but is NOT caused by either a charge for service or a payment: A patient is charged $100 for treatment by the physician. The patient pays $60 and the medical office posts an adjustment to reduce the balance due by $15. What is the balance due on this account? Employers are obligated by law to match which of the following: The most appropriate statement for use in a collection letter is: We will be happy to assist you in making payment arrangements An emancipated minor sees the physician for a scheduled appointment. The charge for service should be: Billed to the patient A written authorization by the patient that allows direct reimbursement to the physician for billed charges is called: Assignment of benefits The person who is covered by a health plan is the: A bill is never sent to a patient with the following coverage: The insurance company pays a certain percentage of the approved amount, with the patient paying the balance due for medical services. The portion that each pays is called the: Part A of Medicare provides coverage for: The mandated claim form to be used for all health insurance claims is the: The term that describes a fixed payment per month to the physician, regardless of the services rendered, is called a: Before a health plan begins to pay benefits, the patient must pay a certain amount of eligible charges each calendar year. This is called: A person is diagnosed with a disease before the effective date of the insurance plan. The insurance plan may determine that under the terms of its contract with the patient, it is not required to pay for any changes associated with the disease. This is called a: Medicare is a federal health insurance program for: Anyone over 65 years of age Medicare Part B covers: Physician office visits The process of determining whether a service or procedure is covered by the insurance provider is called: The medical bills of spouses and children of veterans with total, permanent, service connected disabilities are covered under: To purchase health insurance, the policy holder pays a: A primary care physician, or PCP, is: A physician who agrees to oversee a patient�s care in a managed care plan When an insurance company will not cover a specific condition or circumstance, this is called an: Medicare Part C covers: Managed care plans in Medicare Prescription drug coverage is covered under Medicare: Parents may purchase health insurance for their children under which federal plan administered by the individual states? The coding system used by hospitals to bill for services is known as: - HCPCS (durable medical equipment, home health supplies) The proper code for the term used to describe a cancer that has not invaded neighboring tissue is: CPT stands for: Current Procedural Terminology The primary reason that AMA updates CPT codes annually is: Addition for new and revised codes for services rendered. When is the coding abbreviation NEC (not elsewhere classed) used? When information is not known for specific category coding The appropriate level of E&M coding is determined by all of the elements listed below EXCEPT: - Patient history - Level of examination - Level of presenting problem - NUMBER OF PROCEDURES ORDERED FOR THE PATIENT - Complexity of medical decision making All of the following are associated with procedural coding systems EXCEPT: The concept of RBRVS is used to determine: The values of services performed, practice expenses, and professional liability insurance Dr. Maple is a pediatrician. A patient comes to his office with an ear infection. The patient is also due for a childhood vaccination. The diagnostic codes to be used are: 382.09 and V03.81 The purpose of medical coding includes: - Tracking procedures - Track procedures - Identifying disease trends - Providing data to medical researchers The term for the cause of disease is: A patient has been diagnosed with acute appendicitis. The MA coded the insurance form with the number 540.9. The MA was using which of the systems of coding: Which organization is responsible for producing the CPT code book? American Medical Association A disease or procedure named for a person or place is an: The most appropriate reference source for locating a code for chronic arthritis: ICD-9 code books are revised annually to: Improve specificity of diagnoses Dr. Banyon requests the service of Dr. Oak to assist in the evaluation of a patient�s illness. When Dr. Oak bills for services, the code section to be used is: How many times must a patient visit the physician within a 3-year period for a patient evaluation and management examination to be coded as an established visit, according to CPT coding rules? During an office visit, the patient receives an immunization. Where is the appropriate code most likely to be found in the ICD-9 book? What series of CPT codes refers to Evaluation and Management? The coding system used to document the procedure for removing gallstone is: The largest of the six major sections of the CPT manual that contains codes from 10000 to 69999:	2	7	2	0	0	1	0.848199	3	3,674
Sinusitis Classification and external resources Left-sided maxillar sinusitis marked by an arrow. Note the absence of the air transparency indicating the presence of fluid in contrast to the other side. ICD-10 J01, J32 ICD-9 461, 473 DiseasesDB 12136 eMedicine emerg/536 MeSH D012852 Sinusitis is inflammation of the paranasal sinuses, which may be due to infection, allergy, or autoimmune issues. Most cases are due to a viral infection and resolve over the course of 10 days. It is a common condition; for example, in the United States more than 24 million cases occur annually. - 1 Classification - 2 Signs and symptoms - 3 Causes - 4 Pathophysiology - 5 Diagnosis - 6 Treatment - 7 Epidemiology - 8 References - 9 Further reading - 10 External links Sinusitis can be acute (going on less than four weeks) subacute (4–8 weeks) or chronic (going on for 8 weeks or more). All three types of sinusitis have similar symptoms, and are thus often difficult to distinguish. Acute sinusitis is very common. Roughly ninety percent of adults have had sinusitis at some point in their life. Acute sinusitis is usually precipitated by an earlier upper respiratory tract infection, generally of viral origin. If the infection is of bacterial origin, the most common three causative agents are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Until recently, Haemophilus influenzae was the most common bacterial agent to cause sinus infections. However, introduction of the H. influenza type B (Hib) vaccine has dramatically decreased H. influenza type B infections and now non-typable H. influenza (NTHI) are predominantly seen in clinics. Other sinusitis-causing bacterial pathogens include Staphylococcus aureus and other streptococci species, anaerobic bacteria and, less commonly, gram negative bacteria. Viral sinusitis typically lasts for 7 to 10 days, whereas bacterial sinusitis is more persistent. Approximately 0.5% to 2% of viral sinusitis results in subsequent bacterial sinusitis. It is thought that nasal irritation from nose blowing leads to the secondary bacterial infection. Acute episodes of sinusitis can also result from fungal invasion. These infections are typically seen in patients with diabetes or other immune deficiencies (such as AIDS or transplant patients on immunosuppressive anti-rejection medications) and can be life threatening. With type I diabetes, ketoacidosis causes sinusitis by Mucormycosis. Chronic sinusitis, by definition, lasts longer than three months and can be caused by many different diseases that share chronic inflammation of the sinuses as a common symptom. Symptoms of chronic sinusitis may include any combination of the following: nasal congestion, facial pain, headache, night-time coughing, an increase in previously minor or controlled asthma symptoms, general malaise, thick green or yellow discharge, feeling of facial 'fullness' or 'tightness' that may worsen when bending over, dizziness, aching teeth, and/or halitosis. Each of these symptoms has multiple other possible causes, which should be considered and investigated as well. Unless complications occur, fever is not a feature of chronic sinusitis. Often chronic sinusitis can lead to anosmia, a reduced sense of smell. In a small number of cases, acute or chronic maxillary sinusitis is associated with a dental infection. Vertigo, lightheadedness, and blurred vision are not typical in chronic sinusitis and other causes should be investigated. Chronic sinusitis cases are subdivided into cases with polyps and cases without polyps. When polyps are present, the condition is called chronic hyperplastic sinusitis; however, the causes are poorly understood and may include allergy, environmental factors such as dust or pollution, bacterial infection, or fungus (either allergic, infective, or reactive). Non-allergic factors, such as vasomotor rhinitis, can also cause chronic sinus problems. Abnormally narrow sinus passages, such as having a deviated septum, can impede drainage from the sinus cavities and be a contributing factor. A combination of anaerobic and aerobic bacteria, are detected in conjunction with chronic sinusitis, Staphylococcus aureus (including methicilin resistant S.aureus ) and coagulase-negative Staphylococci. Typically antibiotic treatment provides only a temporary reduction in inflammation, although hyperresponsiveness of the immune system to bacteria has been proposed as a possible cause of sinusitis with polyps (chronic hyperplastic sinusitis). Attempts have been made to provide a more consistent nomenclature for subtypes of chronic sinusitis. The presence of eosinophils in the mucous lining of the nose and paranasal sinuses has been demonstrated for many patients, and this has been termed Eosinophilic Mucin RhinoSinusitis (EMRS). Cases of EMRS may be related to an allergic response, but allergy is not often documented, resulting in further subcategorization into allergic and non-allergic EMRS. A more recent, and still debated, development in chronic sinusitis is the role that fungus plays in this disease. Fungus can be found in the nasal cavities and sinuses of most patients with sinusitis, but can also be found in healthy people as well. It remains unclear if fungus is a definite factor in the development of chronic sinusitis and if it is, what the difference may be between those who develop the disease and those who remain symptom free. Trials of antifungal treatments have had mixed results. There are several paired paranasal sinuses, including the frontal, ethmoid, maxillary and sphenoid sinuses. The ethmoid sinuses is further subdivided into anterior and posterior ethmoid sinuses, the division of which is defined as the basal lamella of the middle turbinate. In addition to the severity of disease, discussed below, sinusitis can be classified by the sinus cavity which it affects: - Maxillary – can cause pain or pressure in the maxillary (cheek) area (e.g., toothache, headache) (J01.0/J32.0) - Frontal – can cause pain or pressure in the frontal sinus cavity (located above eyes), headache (J01.1/J32.1) - Ethmoid – can cause pain or pressure pain between/behind the eyes and headaches (J01.2/J32.2) - Sphenoid – can cause pain or pressure behind the eyes, but often refers to the vertex, or top of the head Recent theories of sinusitis indicate that it often occurs as part of a spectrum of diseases that affect the respiratory tract (i.e., the "one airway" theory) and is often linked to asthma. All forms of sinusitis may either result in, or be a part of, a generalized inflammation of the airway, so other airway symptoms, such as cough, may be associated with it. Signs and symptoms Headache/facial pain or pressure of a dull, constant, or aching sort over the affected sinuses is common with both acute and chronic stages of sinusitis. This pain is typically localized to the involved sinus and may worsen when the affected person bends over or when lying down. Pain often starts on one side of the head and progresses to both sides. Acute and chronic sinusitis may be accompanied by thick nasal discharge that is usually green in colour and may contain pus (purulent) and/or blood. Often a localized headache or toothache is present, and it is these symptoms that distinguish a sinus-related headache from other types of headaches, such as tension and migraine headaches. Infection of the eye socket is possible, which may result in the loss of sight and is accompanied by fever and severe illness. Another possible complication is the infection of the bones (osteomyelitis) of the forehead and other facial bones – Pott's puffy tumor. Sinus infections can also cause inner ear problems due to the congestion of the nasal passages. This can be demonstrated by dizziness, "a pressurized or heavy head", or vibrating sensations in the head. Recent studies suggest that up to 90% of "sinus headaches" are actually migraines.[verification needed] The confusion occurs in part because migraine involves activation of the trigeminal nerves, which innervate both the sinus region and the meninges surrounding the brain. As a result, it is difficult to accurately determine the site from which the pain originates. Additionally, nasal congestion can be a common result of migraine headaches, due to the autonomic nerve stimulation that can also cause in tearing (lacrimation) and a runny nose (rhinorrhea). A study found that patients with "sinus headaches" responded to triptan migraine medications, but stated dissatisfaction with their treatment when they are treated with decongestants or antibiotics. People with migraines do not typically have the thick nasal discharge that is a common symptom of a sinus infection. The close proximity of the brain to the sinuses makes the most dangerous complication of sinusitis, particularly involving the frontal and sphenoid sinuses, infection of the brain by the invasion of anaerobic bacteria through the bones or blood vessels. Abscesses, meningitis, and other life-threatening conditions may result. In extreme cases the patient may experience mild personality changes, headache, altered consciousness, visual problems, seizures, coma, and possibly death. Factors which may predispose someone to developing sinusitis include: allergies; structural abnormalities, such as a deviated septum, small sinus ostia or a concha bullosa; nasal polyps; carrying the cystic fibrosis gene, though research is still tentative; and prior bouts of sinusitis, because each instance may result in increased inflammation of the nasal or sinus mucosa and potentially further narrow the nasal passageways. Second hand smoke may also be associated with chronic rhinosinusitis. Another cause of chronic sinusitis can be from the maxillary sinuses that are situated within the cheekbones. Infections and inflammation are more common here than in any of the other paranasal sinuses. This is because the drainage of mucous secretions from the maxillary sinus to the nasal cavity is not very efficient. Maxillary sinusitis may also be of dental origin and constitutes a significant percentage, given the intimacy of the relationship between the teeth and the sinus floor. Complementary tests based on conventional radiology techniques and modern are needed. Their indication is based on the clinical context. Chronic sinusitis can also be caused indirectly through a common but slight abnormality within the auditory or Eustachian tube, which is connected to the sinus cavities and the throat. This tube is usually almost level with the eye sockets but when this sometimes hereditary abnormality is present, it is below this level and sometimes level with the vestibule or nasal entrance. This almost always causes some sort of blockage within the sinus cavities ending in infection and usually resulting in chronic sinusitis. It has been hypothesized that biofilm bacterial infections may account for many cases of antibiotic-refractory chronic sinusitis. Biofilms are complex aggregates of extracellular matrix and inter-dependent microorganisms from multiple species, many of which may be difficult or impossible to isolate using standard clinical laboratory techniques. Bacteria found in biofilms have their antibiotic resistance increased up to 1000 times when compared to free-living bacteria of the same species. A recent study found that biofilms were present on the mucosa of 75% of patients undergoing surgery for chronic sinusitis. Bacterial and viral acute sinusitis are difficult to distinguish. However, if symptoms last less than 10 days, it is generally considered viral sinusitis. When symptoms last more than 10 days, it is considered bacterial sinusitis (usually 30% to 50% are bacterial sinusitis). Hospital acquired acute sinusitis can be confirmed by performing a CT scan of the sinuses. For sinusitis lasting more than eight weeks, diagnostic criteria are lacking. A CT scan is recommended, but this alone is insufficient to confirm the diagnosis. Nasal endoscopy, a CT scan, and clinical symptoms are all used to make a positive diagnosis. A tissue sample for histology and cultures can also be collected and tested. Allergic fungal sinusitis (AFS) is often seen in people with asthma and nasal polyps. Examining multiple biopsy samples can be helpful to confirm the diagnosis. In rare cases, sinusoscopy may be made. Nasal endoscopy involves inserting a flexible fiber-optic tube with a light and camera at its tip into the nose to examine the nasal passages and sinuses. This is generally a completely painless (although uncomfortable) procedure which takes between five to ten minutes to complete. Nasal irrigation may help with symptoms of chronic sinusitis. Decongestant nasal sprays containing oxymetazoline may provide relief, but these medications should not be used for more than the recommended period. Longer use may cause rebound sinusitis. Other recommendations include applying a warm, moist washcloth several times a day; drinking sufficient fluids in order to thin the mucus and inhaling steam two to four times a day. The vast majority of cases of sinusitis are caused by viruses and will therefore resolve without antibiotics. However, if symptoms do not resolve within 10 days, amoxicillin is a reasonable antibiotic to use first for treatment with amoxicillin/clavulanate (Augmentin) being indicated when the patient's symptoms do not improve on amoxicillin alone. The presence of aerobic and anaerobic beta-lactamase producing organisms may account for this failure. These organisms can "protect" even non beta lactamase producing bacteria from penicillins.Fluoroquinolones, and a newer macrolide antibiotic such as clarithromycin or a tetracycline like doxycycline, are used in patients who are allergic to penicillins. One study found 60 to 90% of people do not experience resolution of maxillary sinusitis using antibiotics., A short-course (3–7 days) of antibiotics seems to be just as effective as the typical longer-course (10–14 days) of antibiotics for patients who present with clinically diagnosed acute-bacterial sinusitis without any other severe disease or complicating factors. For unconfirmed acute sinusitis, intranasal corticosteroids have not been found to be better than placebo either alone or in combination with antibiotics. However for cases confirmed by radiology or nasal endoscopy treatment with corticosteroids alone or in combination with antibiotics is supported. For chronic or recurring sinusitis, referral to an otolaryngologist specialist may be indicated, and treatment options may include nasal surgery. Surgery should only be considered for those patients who do not experience sufficient relief from optimal medication. Maxilliary antral washout involves puncturing the sinus and flushing with saline to clear the mucus. A 1996 study of patients with chronic sinusitis found that washout confers no additional benefits over antiobiotics alone. A relatively recent advance in the treatment of sinusitis is a type of surgery called functional endoscopic sinus surgery (FESS). This surgery removes anatomical and pathological obstructions associated with sinusitis in order to restore normal clearance of the sinuses. This replaces prior open techniques requiring facial or oral incisions and refocuses the technique to the natural openings of the sinuses instead of promoting drainage by gravity, the idea upon which the Caldwell-Luc surgery was based. A number of surgical approaches can be used to access the sinuses and these have generally shifted from external/extranasal approaches to intranasal endoscopic ones. The benefit of the Functional Endoscopic Sinus Surgery FESS is its ability to allow for a more targeted approach to the affected sinuses, reducing tissue disruption, and minimizing post-operative complications. Another recently developed treatment is balloon sinuplasty. This method, similar to balloon angioplasty used to "unclog" arteries of the heart, utilizes balloons in an attempt to expand the openings of the sinuses in a less invasive manner. The utility of this treatment for sinus disease is still under debate but appears promising. For persistent symptoms and disease in patients who have failed medical and the functional endoscopic approaches, older techniques can be used to address the inflammation of the maxillary sinus, such as the Caldwell-Luc radical antrostomy. This surgery involves an incision in the upper gum, opening in the anterior wall of the antrum, removal of the entire diseased maxillary sinus mucosa and drainage is allowed into inferior or middle meatus by creating a large window in the lateral nasal wall.) - ^ a b Anon JB (April 2010). "Upper respiratory infections". Am. J. Med. 123 (4 Suppl): S16–25. doi:10.1016/j.amjmed.2010.02.003. PMID 20350632. - ^ a b http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/rhino-sinusitis/ - ^ Pearlman, AN.; Conley, DB. (June 2008). "Review of current guidelines related to the diagnosis and treatment of rhinosinusitis.". Curr Opin Otolaryngol Head Neck Surg 16 (3): 226–30. doi:10.1097/MOO.0b013e3282fdcc9a. PMID 18475076. - ^ a b c d e f g h i Leung, R.S.; Katial, R. (2008). "The Diagnosis and Management of Acute and Chronic Sinusitis". Primary Care: Clinics in Office Practice 35 (1): 11–24. doi:10.1016/j.pop.2007.09.002. PMID 18206715. http://cimed.ucr.ac.cr/archivos/Articulos%20Interes/2008/marzo/Diagnostico%20y%20Manejo%20de%20la%20Sinusitis%20Aguda.pdf. - ^ Gwaltney, Jr.; Hendley, J. Owen; Phillips, C. Douglas; Bass, Cameron R.; Mygind, Niels; Winther, Birgit (2000). "Nose Blowing Propels Nasal Fluid into the Paranasal Sinuses". Clinical Infectious Diseases 30 (2): 387. doi:10.1086/313661. PMID 10671347. - ^ http://www.austinent.com/info/wiki/sinusitis.php - ^ Gelfand, Jonathan L. "Help for Sinus Pain and Pressure". WebMD.com. http://www.webmd.com/allergies/sinus-pain-pressure-9/sinus-headaches. Retrieved 2 October 2011. - ^ Brook I. Sinusitis. Periodontol 2000. 2009 ; 49:126-39. - ^ Brook I, Frazier EH. Bacteriology of chronic maxillary sinusitis associated with nasal polyposis. J Med Microbiol. 2005 ;54:595-7. - ^ Brook I, Foote PA, Hausfeld JN. Increase in the frequency of recovery of meticillin-resistant Staphylococcus aureus in acute and chronic maxillary sinusitis.J Med Microbiol. 2008;57:1015-7. - ^ Grossman J (1997). "One airway, one disease". Chest 111 (2 Suppl): 11S–16S. doi:10.1378/chest.111.2_Supplement.11S. PMID 9042022. - ^ Cruz AA (2005). "The 'united airways' require an holistic approach to management". Allergy 60 (7): 871–4. doi:10.1111/j.1398-9995.2005.00858.x. PMID 15932375. - ^ a b c University of Maryland - Sinusitus Complications - ^ Itzhak Brook MD. "Sinusitis Understood". Blogspot. http://sinusitisunderstood.blogspot.com/p/epidemology-and-diagnosis.html. - ^ "Sinusitis" (in English). herb2000.com. http://www.herbs2000.com/disorders/sinusitis.htm. "Incidence of acute sinusitis almost always set in following the appearance of a cold for several days at a stretch in the person to the point that all the profuse nasal discharge turns a distinct yellow or a dark green color, or perhaps very thick, and foul-smelling in some cases." - ^ Schreiber C, Hutchinson S, Webster C, Ames M, Richardson M, Powers C (2004). "Prevalence of migraine in patients with a history of self-reported or physician-diagnosed "sinus" headache". Arch. Intern. Med. 164 (16): 1769–72. doi:10.1001/archinte.164.16.1769. PMID 15364670. - ^ Mehle ME, Schreiber CP (2005). "Sinus headache, migraine, and the otolaryngologist". Otolaryngol Head Neck Surg. 133 (4): 489–96. doi:10.1016/j.otohns.2005.05.659. PMID 16213917. - ^ Ishkanian, G; Blumenthal, H; Webster, CJ; Richardson, MS; Ames, M (January 2007). "Efficacy of sumatriptan tablets in migraineurs self-described or physician-diagnosed as having sinus headache: A randomized, double-blind, placebo-controlled study". Clin Ther 29 (1): 99–109. doi:10.1016/j.clinthera.2007.01.012. PMID 17379050. - ^ Headache Classification Subcommittee of the International Headache Society (2004). "The International Classification of Headache Disorders: 2nd edition". Cephalalgia 24 (Suppl 1): 118. doi:10.1111/j.1468-2982.2004.00653.x. PMID 14979299. - ^ Brook I.Microbiology of intracranial abscesses and their associated sinusitis. Arch Otolaryngol Head Neck Surg. 2005; 131:1017-9. - ^ Tammemagi CM, Davis RM, S Benninger M, Holm AL, Krajenta R (April 2010). "Secondhand smoke as a potential cause of chronic rhinosinusitis: a case-control study". Arch. Otolaryngol. Head Neck Surg. 136 (4): 327–34. doi:10.1001/archoto.2010.43. PMID 20403847. - ^ The maxillary sinusitis of dental origin: From diagnosis to treatment Le courrier du dentiste - ^ Palmer JN (2005). "Bacterial biofilms: do they play a role in chronic sinusitis?". Otolaryngol. Clin. North Am. 38 (6): 1193–201, viii. doi:10.1016/j.otc.2005.07.004. PMID 16326178. - ^ Ramadan H, Sanclement J, Thomas J (2005). "Chronic rhinosinusitis and biofilms". Otolaryngol Head Neck Surg 132 (3): 414–7. doi:10.1016/j.otohns.2004.11.011. PMID 15746854. - ^ Bendouah Z, Barbeau J, Hamad W, Desrosiers M (2006). "Biofilm formation by Staphylococcus aureus and Pseudomonas aeruginosa is associated with an unfavorable evolution after surgery for chronic sinusitis and nasal polyposis". Otolaryngol Head Neck Surg 134 (6): 991–6. doi:10.1016/j.otohns.2006.03.001. PMID 16730544. - ^ Bacterial Resistance to Antimicrobials Edited by Kim Lewis. Abagail A. Salyers,Harry W. Taber, and Richard G. Wax . Marcel Decker, New York ,2002 - ^ Sanclement J, Webster P, Thomas J, Ramadan H (2005). "Bacterial biofilms in surgical specimens of patients with chronic rhinosinusitis". Laryngoscope 115 (4): 578–82. doi:10.1097/01.mlg.0000161346.30752.18 (inactive 2009-11-03). PMID 15805862. - ^ Harrison's Manual of Medicine 16/e - ^ Harvey R, Hannan SA, Badia L, Scadding G (2007). Harvey, Richard. ed. "Nasal saline irrigations for the symptoms of chronic rhinosinusitis". Cochrane Database Syst Rev (3): CD006394. doi:10.1002/14651858.CD006394.pub2. PMID 17636843. - ^ 'Rhinitis medicamentosa' by Natalya M Kushnir, MD, Allergy and Immunology Clinic of the East Bay, berkely, CA, Published in eMedicine on Oct 13th, 2009 - ^ http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001670/ - ^ Brook I. Treatment modalities for bacterial rhinosinusitis. Expert Opin Pharmacother. 2010;11:755-69. - ^ Brook I. The role of beta-lactamase-producing-bacteria in mixed infectionsBMC Infect Dis. 2009;9:202. - ^ Karageorgopoulos DE, Giannopoulou KP, Grammatikos AP, Dimopoulos G, Falagas ME (March 2008). "Fluoroquinolones compared with beta-lactam antibiotics for the treatment of acute bacterial sinusitis: a meta-analysis of randomized controlled trials". CMAJ 178 (7): 845–54. doi:10.1503/cmaj.071157. PMC 2267830. PMID 18362380. http://www.cmaj.ca/cgi/pmidlookup?view=long&pmid=18362380. - ^ a b Ian G. Williamson et al. (2007). "Antibiotics and Topical Nasal Steroid for Treatment of Acute Maxillary Sinusitis". JAMA 298 (21): 2487–96. doi:10.1001/jama.298.21.2487. PMID 18056902. - ^ van Buchem, F. L.; Knottnerus, J. A., Schrijnemaekers, V. J. J., Peeters, M. F. (8 March 1997). "Primary-care-based randomised placebo-controlled trial of antibiotic treatment in acute maxillary sinusitis". Lancet 349 (9053): 683–7. doi:10.1016/S0140-6736(96)07585-X. PMID 9078199. - ^ Falagas ME, Karageorgopoulos DE, Grammatikos AP, Matthaiou DK (February 2009). "Effectiveness and safety of short vs. long duration of antibiotic therapy for acute bacterial sinusitis: a meta-analysis of randomized trials". Br J Clin Pharmacol 67 (2): 161–71. doi:10.1111/j.1365-2125.2008.03306.x. PMC 2670373. PMID 19154447. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0306-5251&date=2009&volume=67&issue=2&spage=161. - ^ Zalmanovici A, Yaphe J (2009). Zalmanovici Trestioreanu, Anca. ed. "Intranasal steroids for acute sinusitis". Cochrane Database Syst Rev (4): CD005149. doi:10.1002/14651858.CD005149.pub3. PMID 19821340. - ^ Fokkens W, Lund V, Mullol J (2007). "European Position Paper on Rhinosinusitis and Nasal Polyps 2007". Rhinol Suppl. 16 (20): 67. doi:10.1017/S0959774306000060. PMID 17844873. - ^ Tichenor, Wellington S. (2007-04-22). "FAQ — Sinusitis — WS Tichenor M.D.". http://www.sinuses.com/faq.htm#surgery. Retrieved 2007-10-28. - ^ Pang, Y. T.; Willatt, D. J. (1996). "Do antral washouts have a place in the current management of chronic sinusitis?". The Journal of laryngology and otology 110 (10): 926–928. PMID 8977854. - ^ http://www.fasthealth.com/dictionary/c/Caldwell-Luc_operation.php - ^ Stammberger H (February 1986). "Endoscopic endonasal surgery—concepts in treatment of recurring rhinosinusitis. Part I. Anatomic and pathophysiologic considerations". Otolaryngol Head Neck Surg 94 (2): 143–7. PMID 3083326. - ^ Bailey and Love - ^ Dykewicz MS, Hamilos DL (February 2010). "Rhinitis and sinusitis". J. Allergy Clin. Immunol. 125 (2 Suppl 2): S103–15. doi:10.1016/j.jaci.2009.12.989. PMID 20176255. - Brook I. Editor. Sinusitis from Microbiology to Management. Taylor & Francis Group. New York, London. 2005. Pathology of respiratory system (J, 460–519), respiratory diseases Upper RT Common cold)Headvocal folds: Laryngopharyngeal reflux (LPR) · Vocal fold nodule · Vocal cord paresis · Vocal cord dysfunction Lower RT/lung disease (including LRTIs)acute: Acute bronchitischronic: COPD (Chronic bronchitis, Acute exacerbations of chronic bronchitis, Acute exacerbation of COPD, Emphysema) · Asthma (Status asthmaticus, Aspirin-induced, Exercise-induced) · BronchiectasisInterstitial/ restrictiveBy pathogenBy vector/routeBy distributionBroncho- · LobarOther Other/general Inflammation Acute Chronic Processes Specific locationsCardiovascularDigestivemouth (Stomatitis, Gingivitis, Gingivostomatitis, Glossitis, Tonsillitis, Sialadenitis/Parotitis, Cheilitis, Pulpitis, Gnathitis) · tract (Esophagitis, Gastritis, Gastroenteritis, Enteritis, Colitis, Enterocolitis, Duodenitis, Ileitis, Caecitis, Appendicitis, Proctitis) · accessory (Hepatitis, Cholangitis, Cholecystitis, Pancreatitis) · Peritonitis Common cold Viruses Symptoms Complications Antiviral drugsPleconaril (experimental) Wikimedia Foundation. 2010.	2	36	7	0	1	4	0.389368	12	6,875
Miscarriage Classification and external resources A complete spontaneous abortion at about six weeks from conception, i.e. eight weeks from the last menstrual period (LMP) ICD-10 O03 ICD-9 634 MedlinePlus 001488 eMedicine topic list MeSH D000022 Miscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation. Miscarriage is the most common complication of early pregnancy. - 1 Terminology - 2 Classification - 3 Signs and symptoms - 4 Causes - 5 Diagnosis - 6 Management - 7 Prevention - 8 Epidemiology - 9 In other animals - 10 ICD10 codes - 11 See also - 12 References - 13 External links Very early miscarriages—those that occur before the sixth week LMP (since the woman's Last Menstrual Period)—are medically termed early pregnancy loss or chemical pregnancy. Miscarriages that occur after the sixth week LMP are medically termed clinical spontaneous abortion. In medical (and veterinary) contexts, the word "abortion" refers to any process by which a pregnancy ends with the death and removal or expulsion of the fetus, regardless of whether it is spontaneous or intentionally induced. Many women who have had miscarriages, however, object to the term "abortion" in connection with their experience, as it is generally associated with induced abortions. In recent years there has been discussion in the medical community about avoiding the use of this term in favor of the less ambiguous term "miscarriage". In 2005 the European Society for Human Reproduction and Embryology (ESHRE) published a paper aiming to facilitate an update and revision of nomenclature used to describe early pregnancy events. Labour resulting in live birth before the 37th week of pregnancy is termed "premature birth", even if the infant dies shortly afterward. The limit of viability at which 50% of fetus/infants survive longterm is around 24 weeks, with moderate or major neurological disability dropping to 50% only by 26 weeks. Although long-term survival has never been reported for infants born from pregnancy shorter than 21 weeks and 5 days, fetuses born as early as the 16th week of pregnancy may sometimes live for some minutes after birth. A fetus that dies while in the uterus after about the 20–24th week of pregnancy is termed a "stillbirth"; the precise gestational age definition varies by country. Premature births or stillbirths are not generally considered miscarriages, though usage of the terms and causes of these events may overlap. Miscarriage of a fetus is also called intrauterine fetal death (IUFT). The clinical presentation of a threatened abortion describes any bleeding seen during pregnancy prior to viability, that has yet to be assessed further. At investigation it may be found that the fetus remains viable and the pregnancy continues without further problems. It has been suggested that bed rest improves the chances of the pregnancy continuing when a small subchorionic hematoma has been found on ultrasound scans. Alternatively the following terms are used to describe pregnancies that do not continue: - An empty sac is a condition where the gestational sac develops normally, while the embryonic part of the pregnancy is either absent or stops growing very early. Other terms for this condition are blighted ovum and anembryonic pregnancy. - An inevitable abortion describes a condition in which the cervix has already dilated open, but the fetus has yet to be expelled. This usually will progress to a complete abortion. The fetal heart beat may have been shown to have stopped, but this is not part of the criteria. - A complete abortion is when all products of conception have been expelled. Products of conception may include the trophoblast, chorionic villi, gestational sac, yolk sac, and fetal pole (embryo); or later in pregnancy the fetus, umbilical cord, placenta, amniotic fluid, and amniotic membrane. - An incomplete abortion occurs when tissue has been passed, but some remains in utero. - A missed abortion is when the embryo or fetus has died, but a miscarriage has not yet occurred. It is also referred to as delayed or missed miscarriage. The following two terms consider wider complications or implications of a miscarriage: - A septic abortion occurs when the tissue from a missed or incomplete abortion becomes infected. The infection of the womb carries risk of spreading infection (septicaemia) and is a grave risk to the life of the woman. - Recurrent pregnancy loss (RPL) or recurrent miscarriage (medically termed habitual abortion) is the occurrence of three consecutive miscarriages. If the proportion of pregnancies ending in miscarriage is 15%, then the probability of two consecutive miscarriages is 2.25% and the probability of three consecutive miscarriages is 0.34%. The occurrence of recurrent pregnancy loss is 1%. A large majority (85%) of women who have had two miscarriages will conceive and carry normally afterwards. The physical symptoms of a miscarriage vary according to the length of pregnancy: - At up to six weeks only small blood clots may be present, possibly accompanied by mild cramping or period pain. - At 6 to 13 weeks a clot will form around the embryo or fetus, and the placenta, with many clots up to 5 cm in size being expelled prior to a completed miscarriage. The process may take a few hours or be on and off for a few days. Symptoms vary widely and can include vomiting and loose bowels, possibly due to physical discomfort. - At over 13 weeks the fetus may be easily passed from the womb, however the placenta is more likely to be fully or partially retained in the uterus, resulting in an incomplete abortion. The physical signs of bleeding, cramping and pain can be similar to an early miscarriage, but sometimes more severe and labour-like. Signs and symptoms The most common symptom of a miscarriage is bleeding; bleeding during pregnancy may be referred to as a threatened abortion. Of women who seek clinical treatment for bleeding during pregnancy, about half will go on to have a miscarriage. Symptoms other than bleeding are not statistically related to miscarriage. Miscarriage may also be detected during an ultrasound exam, or through serial human chorionic gonadotropin (HCG) testing. Women pregnant from ART methods, and women with a history of miscarriage, may be monitored closely and so detect a miscarriage sooner than women without such monitoring. Several medical options exist for managing documented nonviable pregnancies that have not been expelled naturally. Although a woman physically recovers from a miscarriage quickly, psychological recovery for parents in general can take a long time. People differ greatly in this regard: some are able to move on after a few months, but others take more than a year. Still others may feel relief or other less negative emotions. A questionnaire (GHQ-12 General Health Questionnaire) study following women having miscarried showed that half (55%) of the miscarrying women presented with significant psychological distress immediately, 25% at 3 months; 18% at 6 months, and 11% at 1 year after miscarriage. For those who do go through a process of grief, it is often as if a baby had been born but died. How short a time the fetus lived in the womb may not matter for the feeling of loss. From the moment pregnancy is discovered, the parents can start to bond with the embryo or fetus. When the pregnancy turns out not to be viable, dreams, fantasies and plans for the future are roughly disturbed. Besides the feeling of loss, a lack of understanding by others is often important. People who have not experienced a miscarriage themselves may find it hard to empathize with what has occurred and how upsetting it may be. This may lead to unrealistic expectations of the parents' recovery. The pregnancy and miscarriage are hardly mentioned any more in conversation, often because the subject is too painful. This can make the woman feel particularly isolated. Inappropriate or insensitive responses from the medical profession can add to the distress and trauma experienced, so in some cases attempts have been made to draw up a standard code of practice. Interaction with pregnant women and newborn children is often also painful for parents who have experienced miscarriage. Sometimes this makes interaction with friends, acquaintances and family very difficult. Miscarriages can occur for many reasons, not all of which can be identified. Some of these causes include genetic, uterine or hormonal abnormalities, reproductive tract infections, and tissue rejection. Chromosomal abnormalities are found in more than half of embryos miscarried in the first 13 weeks. A pregnancy with a genetic problem has a 95% probability of ending in miscarriage. Most chromosomal problems happen by chance, have nothing to do with the parents, and are unlikely to recur. Chromosomal problems due to a parent's genes are, however, a possibility. This is more likely to have been the cause in the case of repeated miscarriages, or if one of the parents has a child or other relatives with birth defects. Genetic problems are more likely to occur with older parents; this may account for the higher miscarriage rates observed in older women. Another cause of early miscarriage may be progesterone deficiency. Women diagnosed with low progesterone levels in the second half of their menstrual cycle (luteal phase) may be prescribed progesterone supplements, to be taken for the first trimester of pregnancy. No study has shown that general first-trimester progesterone supplements reduce the risk of threatened miscarriage (when a mother might already be losing her baby), and even the identification of problems with the luteal phase as contributing to miscarriage has been questioned. Up to 15% of pregnancy losses in the second trimester may be due to uterine malformation, growths in the uterus (fibroids), or cervical problems. These conditions may also contribute to premature birth. One study found that 19% of second trimester losses were caused by problems with the umbilical cord. Problems with the placenta may also account for a significant number of later-term miscarriages. General risk factors Pregnancies involving more than one fetus are at increased risk of miscarriage. Uncontrolled diabetes greatly increases the risk of miscarriage. Women with controlled diabetes are not at higher risk of miscarriage. Because diabetes may develop during pregnancy (gestational diabetes), an important part of prenatal care is to monitor for signs of the disease. Polycystic ovary syndrome is a risk factor for miscarriage, with 30-50% of pregnancies in women with PCOS being miscarried in the first trimester. Two studies have shown treatment with the drug metformin to significantly lower the rate of miscarriage in women with PCOS (the metformin-treated groups experienced approximately one-third the miscarriage rates of the control groups). However, a 2006 review of metformin treatment in pregnancy found insufficient evidence of safety and did not recommend routine treatment with the drug. High blood pressure during pregnancy, known as preeclampsia, is sometimes caused by an inappropriate immune reaction (paternal tolerance) to the developing fetus, and is associated with the risk of miscarriage. Similarly, women with a history of recurrent miscarriages are at risk of developing preeclampsia. Severe cases of hypothyroidism increase the risk of miscarriage. The effect of milder cases of hypothyroidism on miscarriage rates has not been established. The presence of certain immune conditions such as autoimmune diseases is associated with a greatly increased risk of miscarriage. The presence of anti-thyroid autoantibodies is associated with an increased risk of miscarriage with an odds ratio of 3.73 and 95% confidence interval 1.8–7.6. Tobacco (cigarette) smokers have an increased risk of miscarriage. An increase in miscarriage is also associated with the father being a cigarette smoker. The husband study observed a 4% increased risk for husbands who smoke fewer than 20 cigarettes/day, and an 81% increased risk for husbands who smoke 20 or more cigarettes/day. Cocaine use increases miscarriage rates. Physical trauma, exposure to environmental toxins, and use of an IUD during the time of conception have also been linked to increased risk of miscarriage. Suspected risk factors Several factors have been correlated with higher miscarriage rates, but whether they cause miscarriages is debated. No causal mechanism may be known, the studies showing a correlation may have been retrospective (beginning the study after the miscarriages occurred, which can introduce bias) rather than prospective (beginning the study before the women became pregnant), or both. Some research suggests autoimmunity as a possible cause of recurrent or late-term miscarriages. Autoimmune disease occurs when the body's own immune system acts against itself. Therefore, in the case of an autoimmune-induced miscarriage the woman's body attacks the growing fetus or prevents normal pregnancy progression. Further research has also suggested that autoimmune disease can cause genetic abnormalities in embryos which in turn can lead to miscarriage. Nausea and vomiting of pregnancy (NVP, or morning sickness) are associated with a decreased risk of miscarriage. Several mechanisms have been proposed for this relationship, but none are widely agreed on. Because NVP may alter a woman's food intake and other activities during pregnancy, it may be a confounding factor when investigating possible causes of miscarriage. One such factor is exercise. A study of over 92,000 pregnant women found that most types of exercise (with the exception of swimming) correlated with a higher risk of miscarriage prior to 18 weeks. Increasing time spent on exercise was associated with a greater risk of miscarriage: an approximately 10% increased risk was seen with up to 1.5 hours per week of exercise, and a 200% increased risk was seen with over 7 hours per week of exercise. High-impact exercise was especially associated with the increased risk. No relationship was found between exercise and miscarriage rates after the 18th week of pregnancy. The majority of miscarriages had already occurred at the time women were recruited for the study, and no information on nausea during pregnancy or exercise habits prior to pregnancy was collected. Caffeine consumption has also been correlated to miscarriage rates, at least at higher levels of intake. A 2007 study of over 1,000 pregnant women found that women who reported consuming 200 mg or more of caffeine per day experienced a 25% miscarriage rate, compared to 13% among women who reported no caffeine consumption. 200 mg of caffeine is present in 10 oz (300 mL) of coffee or 25 oz (740 mL) of tea. This study controlled for pregnancy-associated nausea and vomiting (NVP or morning sickness): the increased miscarriage rate for heavy caffeine users was seen regardless of how NVP affected the women. About half of the miscarriages had already occurred at the time women were recruited for the study. A second 2007 study of approximately 2,400 pregnant women found that caffeine intake up to 200 mg per day was not associated with increased miscarriage rates (the study did not include women who drank more than 200 mg per day past early pregnancy). A prospective cohort study in 2009 showed no increased risk. A miscarriage can be confirmed via ultrasound and by the examination of the passed tissue. When looking for microscopic pathologic symptoms of miscarriage, one looks for the products of conception. Microscopically, these include villi, trophoblast, fetal parts, and background gestational changes in the endometrium. Genetic tests may also be performed to look for abnormal chromosome arrangements. Blood loss during early pregnancy is the most common symptom of both miscarriage and of ectopic pregnancy. Pain does not strongly correlate with miscarriage, but is a common symptom of ectopic pregnancy. In the case of concerning blood loss, pain, or both, transvaginal ultrasound is performed. If a viable intrauterine pregnancy is not found with ultrasound, serial βHCG tests should be performed to rule out ectopic pregnancy, which is a life-threatening situation. If the bleeding is light, making an appointment to see one's doctor is recommended. If bleeding is heavy, there is considerable pain, or there is a fever, then emergency medical attention is recommended to be sought. No treatment is necessary for a diagnosis of complete abortion (as long as ectopic pregnancy is ruled out). In cases of an incomplete abortion, empty sac, or missed abortion there are three treatment options: - With no treatment (watchful waiting), most of these cases (65–80%) will pass naturally within two to six weeks. This path avoids the side effects and complications possible from medications and surgery. - Medical management usually consists of using misoprostol (a prostaglandin, brand name Cytotec) to encourage completion of the miscarriage. About 95% of cases treated with misoprostol will complete within a few days. - Surgical treatment (most commonly vacuum aspiration, sometimes referred to as a D&C or D&E) is the fastest way to complete the miscarriage. It also shortens the duration and heaviness of bleeding, and avoids the physical pain associated with the miscarriage. In cases of repeated miscarriage, D&C is also the most convenient way to obtain tissue samples for karyotype analysis (cytogenetic or molecular), although it is also possible to do with expectant and medical management. D&C, however, has a higher risk of complications, including risk of injury to the cervix (e.g. cervical incompetence) and uterus, perforation of the uterus, and potential scarring of the intrauterine lining (Asherman's syndrome). This is an important consideration for women who would like to have children in the future and want to preserve their fertility and reduce the chance of future obstetric complications. Currently there is no known way to prevent an impending miscarriage. However, fertility experts believe that identifying the cause of the miscarriage may help prevent it from happening again in a future pregnancy. In one study, researchers found that use of the supplement dehydroepiandrosterone before and during pregnancy reduced the risk of pregnancy losses. Determining the prevalence of miscarriage is difficult. Many miscarriages happen very early in the pregnancy, before a woman may know she is pregnant. Treatment of women with miscarriage at home means medical statistics on miscarriage miss many cases. Prospective studies using very sensitive early pregnancy tests have found that 25% of pregnancies are miscarried by the sixth week LMP (since the woman's Last Menstrual Period). However, other sources reports suggest higher rates. One fact sheet from the University of Ottawa states, "The incidence of spontaneous abortion is estimated to be 50% of all pregnancies, based on the assumption that many pregnancies abort spontaneously with no clinical recognition." The NIH reports, "It is estimated that up to half of all fertilized eggs die and are lost (aborted) spontaneously, usually before the woman knows she is pregnant. Among those women who know they are pregnant, the miscarriage rate is about 15-20%." Clinical miscarriages (those occurring after the sixth week LM) occur in 8% of pregnancies. The risk of miscarriage decreases sharply after the 10th week LMP, i.e. when the fetal stage begins. The loss rate between 8.5 weeks LMP and birth is about two percent; loss is “virtually complete by the end of the embryonic period." The prevalence of miscarriage increases considerably with age of the parents. One study found that pregnancies from men younger than 25 years are 40% less likely to end in miscarriage than pregnancies from men 25–29 years. The same study found that pregnancies from men older than 40 years are 60% more likely to end in miscarriage than the 25–29-year age group. Another study found that the increased risk of miscarriage in pregnancies from older men is mainly seen in the first trimester. Yet another study found an increased risk in women, by the age of 45, on the order of 800% (compared to the 20–24 age group in that study), 75% of pregnancies ended in miscarriage. In other animals Miscarriage occurs in all animals that experience pregnancy. There are a variety of known risk factors for miscarriage in non-human animals. For example, in sheep, it may be caused by crowding through doors, or being chased by dogs. In cows, miscarriage (i.e. spontaneous abortion) may be caused by contagious disease, such as Brucellosis or Campylobacter, but can often be controlled by vaccination. Other diseases are also known to target animals for miscarriage. 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PMID 19324836. http://rspb.royalsocietypublishing.org/content/early/2009/02/21/rspb.2008.1780.abstract. - Pregnancy loss support groups at the Open Directory Project - UnspokenGrief ™.com \| understanding & support for miscarriage survivors. support network Pathology of pregnancy, childbirth and the puerperium (O, 630–679) PregnancyPregnancy with abortive outcomeOedema, proteinuria and hypertensive disordersOther, predominantly related to pregnancyGestational thrombocytopenia · Pregnancy-induced hypercoagulabilityamniotic fluid (Polyhydramnios, Oligohydramnios) · chorion/amnion (Chorioamnionitis, Chorionic hematoma, Premature rupture of membranes, Amniotic band syndrome, Monoamniotic twins) · placenta (Placenta praevia, Placental abruption, Monochorionic twins, Twin-to-twin transfusion syndrome, Circumvallate placenta) · Braxton Hicks contractions · Hemorrhage (Antepartum) Labor Puerperal Other Wikimedia Foundation. 2010.	2	62	11	0	2	2	0.517602	15	9,512
This essay has been submitted by a student. This is not an example of the work written by our professional essay writers. Spirometer is an instrument which is used to measure the volume and capacity of lung. It collects the air expired by the patient to measure the lung volume or capacity. The spirometer has a device attached to it which will measure the movement of gas in and out of chest and this device is called as Spirograph. And in some spirometers, spirographs are replaced by printer called Spirogram. In most of the computerized system the spirographs or the spirogram will display the predicted value next to the observed value. Using spirometer various tests are carried out to determine whether the patient is having any respiratory disorder or not. The purpose of the project is to develop a spirometer which is of very low cost and can be used in rural health care centers, private clinicians and primary function laboratories to detect whether the patient is having any respiratory disorder or not by carrying out three basic tests- Tidal Volume(TV)-The amount of air that is breathed in and out by an individual during normal respiration. Forced Vital Capacity(FVC)-The amount of air that is maximally forced out of the lung after maximum inspiration. Forced Expiratory Volume In 1sec(FEV1)- The amount of air that can be maximally forced out of the lung in the first second of forced expiratory manuever. 1.3 OBJECTIVE OF THE PROJECT To design a low cost microcontroller based spirometer and carry out the various lung functioning tests. To develop a program for the microcontroller to measure the lung volume and display the results digitally on a LCD interfaced with it. RESPIRATORY DISORDER : SYMPTOMS & CAUSES 2.1 RESPIRATORY DISORDER Respiratory disorder Â deals with theÂ diseasesÂ of theÂ respiratory system which include diseases of theÂ lung,Â pleural cavity and bronchialÂ tube. Respiratory diseases range from mild to life-threatening such asÂ bacterial pneumoniaÂ orÂ pulmonary embolism which may lead to illness and death. The study of respiratory E:\Documents and Settings\SSN\Desktop\Project\respiratory-system.jpg disease is known asÂ pulmonology. A doctor who specializes in respiratory disease is known as a pulmonologist. Fig 2.1 RESPIRATORY SYSTEM Some of the common respiratory diseases are : Inflammatory lung disease. Obstructive lung disease. Restrictive lung disease. Pleural cavity diseases. Respiratory tract infection. Pulmonary vascular disease. 2.2 OBSTRUCTIVE LUNG DISEASE Obstructive lung diseasesÂ are diseases of the lung in which theÂ bronchialÂ tubes become narrowed.E:\Documents and Settings\SSN\Desktop\Project\healthy-vs-copd.jpg Two examples for obstructive lung disease are : Chronic Obstructive Pulmonary Disease (COPD) is a disease in which the airways become damaged and hence making them narrow. Asthma causes obstruction to the airflow out of the lungs.And the obstruction is reversible.Â Fig 2.2 COPD SputumÂ or mucus production. 2.3 RESITRICTIVE LUNG DISEASE Restrictive lung diseaseÂ is also known asÂ restrictive ventilatory which restricts the lung expansion and there by decreases the lung volume and increases work of breathing.adam_lung_emphysema.jpg Fig 2.3 EMPHYSEMA Shortness of breath,cough. Asbestos isÂ caused by long-term exposure to asbestos dust. Radiation fibrosis(radiation used for cancer treatment). 2.4 DIAGNOSIS OF ABNORMALITY OF RESPIRATORY SYSTEM USING FEV1/FVC RATIO In restrictive lung disease, bothÂ FEV1Â andÂ FVCÂ are reduced so theÂ FEV1/FVC ratioÂ is normal. In obstructive lung diseaseÂ FEV1Â is reduced while theÂ FVCÂ is normal thus theÂ FEV/FVC ratio is lower. TABLE-2.4.1 FEV1 RATIO AND ITS SEVERITY â‰¥ 80% of predicted 60-80% of predicted 40-60% of predicted â‰¤ 40% of predicted TABLE-2.4.2 FVC RATIO AND ITS SEVERITY > 80% of predicted 60-80% of predicted 50-60% of predicted > 50% of predicted Agarwal.V Ramachandran N.C.S, The patient exhales through the mouthpiece where the gas exchange is being acquired as the voltage signal by the transducer(sensor). This signal from the sensor is amplified by an instrumentation amplifier(INA 114). Then the amplified signal is filtered using a low-pass-filter which is then given to a ADC(ADS7812) for digitisation. After digitisation it is given to the microcontroller(Intel) from which the data is displayed on the LCD screen. For further communication on internet, ETHERNET device is used. The output voltage from the amplifier is digitised using ADC which corresponds to the pressure difference across mouthpiece is computed by the microcontroller and displayed on the LCD screen. In future the system is expected to be inexpensive medical care for thousands of patient. Dr.David Van Sickle et.al, Initially the patient is allowed to expire through the spirometer. The spirometer consists of a pressure sensor(HW 24) which gives a DC voltage as output. This DC voltage is propotional to the pressure drop between the leads which is recorded by the spirometer. This analog data is then converted to digital using ZMD 31014 "iLite" chip. Microcontroller(PIC18f13k50) is used to convert the digital data to USB. Using mathematical algorithm implemented in the computer it calculates the volume and displays on the screen. Graphical display of flow vs volume is evaluated and monitored from which the following values can be calculated :PEF,FVC, FEV(t) and FEV1/FVC ratio. The patient exhales the air through the mouthpiece which consists of a flow sensor, differential pressure sensor, instrumentation amplifier,low pass filter and ADC. The flow sensor relates the velocity and the pressure of air blown if there is no air flow through the sensor the velocity is converted to pressure and this pressure difference is sensed by the difference flow sensor which inturn provide the electrical quantity of the air flow. Inorder to remove noise and amplify the signal an instrumentation amplifier is used. The signal is then fed to the band pass filter of the range 0.05Hz to 1.3Hz,where the spirometer lies in the range of 0.1Hz to 12Hz. The filtered signal is digitised using ADC and this data is read by a microcontroller which is then interfaced to a computer. Commonly measured parameters are FVC,FEV1,TV and MVV then the ratio FEV1 to FVC is calculated and monitored on the screen. Depending on these values we determine whether the patient is normal (or) suffering from either restrictive (or) obstructive disorder. The test is performed using wedge bellow type spirometer the FVC and FEV1 data collected are investigated where the test is performed on different patient and are grouped accordingly. Then a mathematical modeling process is carried out based on fuzzy values obtained from the flow graphs. These values for the subject with COPD is compared with healthy subject belonging to same age,sex and height. The compared values are normalized for fuzzy labels i.e; they are labeled as follows 'Very low','low','Normal','High','Very High'which is the generated on rule base and simulated. Provide the interrelationship between characteristic constants obtained from the curves and degree of disease from which the FEV1 values are measured. In future it eliminates the error factors and helps in accurate diagnosis. OVERVIEW OF THE PROJECT 4.1 BLOCK DIAGRAM Fig 4.1 BLOCK DIAGRAM 4.2 PRINCIPLE OF WORKING The spirometer consists of a turbine flow sensor containing LED(source) on one side and a photo-diode(detector) on the opposite side. Inbetween the LED and the detector there is a rotor. The rotor is a fan like structure with 3 fins. The above arrangement is present inside a cylindrical case which is opened on both the sides. The LED and the photo-diode are molded with a light weight plastic design inside the case. A mouth piece is fitted on one side and the opposite side is kept open. When the patient blows air inside the mouth piece a pressure difference is created due to the atmospheric air(atmospheric pressure) that enters from the opposite side. A power supply circuit is designed to provide power supply to the spirometer. When the patient exhales through the mouth piece the rotor rotates. Whenever the rotor is in-between the source and the detector the light from the source is not detected by the detector and when the rotor is not in-between them then the light from the source is detected by the detector. Each pulse will be detected only if 7ml of gas has been exhaled by the patient. These pulses are then given to the comparator which will give binary output only if the patient is exhaling. And when the patient is not exhaling there is no output from the comparator. This ouput is then given to a microcontroller which is programmed in such a way that it will count the number of pulses from the comparator and these pulses are converted into total number of rotations by dividing them(no of pulses) by 3(since the rotor has 3 fins). These rotations are then used to measure the lung volume. The lung volume is then displayed on a LCD which is interfaced with the microcontroller as digital output. 5.1 ELECTRONIC CIRCUIT po.bmpFig 5.1.1 POWER SUPPLY CIRCUIT Fig 5.1.2 POTENTIAL DIVIDER AND COMPARATOR CIRCUIT Fig 5.1.3 MICROCONTROLLER & LCD DISPLAY 5.1.1 POWER SUPPLY CIRCUIT A 12V and a 5V power supply circuit was implemented. 188.8.131.52 STEP-DOWN TRANSFORMER Transformer being used is a 230V-step down transformer. It converts AC to AC without any change in frequency 184.108.40.206 BRIDGE RECTIFIER The diode used is IN4007 which acts as bridge rectifier and converts the given AC current to DC. 220.127.116.11 IC 7812 & IC 7805 The two ICs are used to provide 12V and 5V supply respectively. 12V from IC7812 is given to the turbine flow sensor. 5V from IC7805 is given to LM324 & Microcontroller The sensor used here is FT-330 Turbine flow sensor.The input to the sensor is the air blown by the patient. Can withstand temperature upto 80 degree celcius. Molded with electronics and a light weight plastic design. 5.1.3 POTENTIAL DIVIDER AND ZENER DIODE The output of the turbine flow sensor is given to the potential divider. The potential divider will reduce 12V from the turbine flow sensor and allows a reduced voltage to zener diode. The zener diode is used to fix a threshold i.e it allows only voltage within 5V to the comparator. LM324 acts as a comparator which gives a voltage within 5V(square wave) when the patient exhales through the sensor. And when the patient does not exhale, the comparator output gets reduced to 0V.The output of the comparator is given to the microcontroller. Internally frequency compensated for unity gain. Large DC voltage gain of 100 dB. Wide bandwidth (unity gain) 1 MHZ. Wide power supply range: Single supply 3V to 32Vor dual supplies Â±1.5V to Â±16V. Eliminates need for dual supplies. Four internally compensated op amps in a single package. Power drain suitable for battery operation. The microcontroller used here is 16F877A. The microcontroller receives input from LM324. The microcontroller is programmed in such a way that it will count the number of pulses from the comparator and these pulses are converted into total number of rotations by dividing them(no of pulses) by 3(since the rotor has 3 fins).These rotations are then used to measure the lung volume(TV,FVC,FEV1). PROGRAM MEMORY=8Kilo bytes This IC can be reprogrammed and erased up to 10,000 times. It is very cheap.It can also be very easily assembled. Additional components needed to make this IC work is a 5V power supply , 20MHz crystal oscillator and two 22pF capacitors. 5.1.6 LCD DISPLAY The output(TV,FVC,FEV1)from the microcontroller is displayed on the LCD according to the program. 5.2 MECHNICAL DESIGN( MATERIALS USED): 5.2.1.TURBINE FLOW SENSOR FT-330 Turbine flow sensor Highly accurate, compact and reliable. Can withstand temperature upto 80 degree celcius. Molded with electronics and a light weight plastic design. 5.2.2. MOUTH PIECE Made up of plastic with a diameter of 2cm. E:\Documents and Settings\SSN\My Documents\My Pictures\Picture\Picture 001.jpg Fig 18.104.22.168 MOUTH PIECE 6.1 OVERVIEW OF CIRCUIT WORKING Initially the patient is allowed to blow through the sensor and the output voltage from the sensor is given as input to the potential divider circuit which limits the current to zener diode and which in turn reduces 12V supply from the potential divider output and allows only 5V to be given to the inverting terminal of LM324(comparator). Reference voltage is given to pin 3 which gets the feedback from LM324 output. Hence when the patient doesn't blow, a high voltage is received by pin 2(inverting terminal) which is compared with the reference voltage ,since the input voltage is greater than reference voltage we get a low voltage(0V) at the output and no pulse is seen and when the patient blows, input voltage is less than reference voltage so we get a high voltage at the output and a train of pulses can be seen. Then the LM324 output is given to the microcontroller(pin 33) and the final values are displayed on the LCD screen 6.2 CIRCUIT TESTING Fig6.2.1 BREADBOARD CONNECTION Fig6.3.1 OUTPUT FROM SENSOR(TV) Fig6.3.2 OUTPUT FROM SENSOR(FVC) Fig6.3.3 OUTPUT FROM SENSOR(FEV1) Fig 6.3.4 OUTPUT FROM COMPARATOR(TV) Fig 6.3.5 OUTPUT FROM COMPARATOR(FVC) Fig 6.3.6 OUTPUT FROM COMPARATOR(FEV1) Fig6.3.7 LCD DISPLAY(TV) Fig6.3.8 LCD DISPLAY(FVC) Fig6.3.9 LCD DISPLAY(FEV1) 1.Initialize the count to 0. 2.When the patient exhales, the number of pulses from LM324 will be counted i.e.; the count gets incremented. 3.This count is converted into rotations since the rotor has 3 fins, if we get 3 pulse, it is considered as 1 rotation. So by dividing the count by 3 we will get the total number of rotations. 4.The LM324 will give 1 pulse only if 7 ml of gas is exhaled . So the total number of rotations is multiplied by 7 to obtain the lung volume. 5.Initially the flag will be 0.When the patient exhales TV will be displayed. 6.When the reset is done the flag will be 1.Now when the patient exhales FVC will be displayed . 7.When the reset is done again the flag will be 2.Now when the patient exhales FEV1 will be displayed .Again when the reset is done and the patient exhales then TV will be displayed. 7.2 EXPERIMENTAL ANALYSIS TABLE-7.2.1 NORMAL VALUES OF TV,FVC AND FEV1 FOR MALE AND FEMALE(Age=20 to25) TABLE-7.2.2 TV,FVC AND FEV1 RESULTS FOR FEMALE(Age,20 to25) 7.3.1 TEST RESULT FOR SUBJECT 1 E:\Documents and Settings\SSN\Desktop\Project\Respi\FVC(raa).bmp Fig 22.214.171.124 FVC VALUES E:\Documents and Settings\SSN\Desktop\Project\Respi\Graphraa.bmp Fig 126.96.36.199 FVC GRAPH E:\Documents and Settings\SSN\Desktop\Project\Respi\SVC(Raa).bmp Fig 188.8.131.52 SVC GRAPH 7.3.2 TEST RESULT FOR SUBJECT 2 E:\Documents and Settings\SSN\Desktop\Project\Respi\FVC(r).bmp Fig 184.108.40.206 FVC VALUES E:\Documents and Settings\SSN\Desktop\Project\Respi\Graphr.bmp Fig 220.127.116.11 FVC GRAPH E:\Documents and Settings\SSN\Desktop\Project\Respi\SVC(R).bmp Fig 18.104.22.168 SVC GRAPH 7.3.3 TEST RESULT FOR SUBJECT 3 E:\Documents and Settings\SSN\Desktop\Project\Respi\FVC(s).bmp Fig 22.214.171.124 FVC VALUES E:\Documents and Settings\SSN\Desktop\Project\Respi\GraphS.bmp Fig 126.96.36.199 FVC GRAPH E:\Documents and Settings\SSN\Desktop\Project\Respi\SVC(SNew).bmp Fig 188.8.131.52 SVC GRAPH 7.3.4 TEST RESULT FOR SUBJECT 4 C:\Users\hi\AppData\Local\Microsoft\Windows\Temporary Internet Files\Content.Word\FVC(t).bmp Fig 184.108.40.206 FVC VALUES C:\Users\hi\AppData\Local\Microsoft\Windows\Temporary Internet Files\Content.Word\Grapht.bmp Fig 220.127.116.11 FVC GRAPH C:\Users\hi\AppData\Local\Microsoft\Windows\Temporary Internet Files\Content.Word\SVC(T).bmp Fig 18.104.22.168 SVC GRAPH TABLE-7.3 COMPARISON OF TESTS RESULTS OBTAINED USING HELIOS PULMONARY FUNCTION TEST AND FROM DESIGNED SPIROMETER (FOR FEMALE,AGE=21) HELIOS PULMONARY FUNCTION TEST HELIOS PULMONARY FUNCTION TEST Thus the tests results obtained from the designed spirometer matches with the tests results obtained from the laboratory spirometer. Minor differences in the value is due to effect of surrounding environment and moving air. CONCLUSION AND FUTURE WORK The objective of the project was to design a low cost spirometer for the rural health care centers, private clinicians and primary function laboratories. In order to substantiate the objective of our work, we compared the market price of currently available spirometer(MIR SpiroDoc Spirometer), the starting price of which is around $1974.50. TABLE-8.1 COST OF EACH COMPONENT Turbine flow sensor Total cost:Rs 2000/- Thus the tests results of four subjects obtained from the designed spirometer was compared with the tests results obtained from HELIOS Pulmonary Function test. The values had some minor differences due to effect of surrounding environment and moving air. But they were of acceptable accuracy. 8.2 FUTURE WORK Future work involves interfacing the device with PC and implementation of the product in Telemedicine application for distance monitoring of respiratory parameters. PIN CONFIGURATION OF LM324(COMPARATOR) PIN CONFIGURATION OF PIC16F877A chip pinout PIC16F877A OVERVIEW OF PIC 16F877A PIC16F877A at a glance	4	8	1	0	0	0	0.67747	1	4,572
This research study examined the usefulness of the ICD-10-CM system in capturing public health diseases (reportable diseases or the nationally notifiable infectious diseases, leading causes of death, and morbidity/mortality related to terrorism), when compared to ICD-9-CM. 1-3 It also examined agreement levels of coders when coding public health diseases in both ICD-10-CM and ICD-9-CM. Overall results demonstrate that ICD-10-CM is more specific and fully captures more of the public health diseases examined than ICD-9-CM. In the analysis of all the public health diseases, such as reportable diseases (p<0.001), top 10 causes of death (p<0.001), and those related to terrorism (p<0.001), it was found that the overall rankings for disease capture for ICD-10-CM were significantly higher than the rankings for ICD-9-CM. When examining whether diseases were captured more straightforwardly and clearly (regarding agreement levels) between coding systems, statistically significant differences were found for external causes of injury (p<0.001), diabetes (average rank only, p<0.05), lower respiratory disease (p<0.001), heart disease (p<0.001), and malignant neoplasms (p<0.05). Although this result may be due to the coder’s higher level of experience with ICD-9-CM, it also points to the potential need for more specific coding education and practice with the ICD-10-CM system. Key Words: public health, ICD-10-CM, ICD-9-CM, agreement, capture, reportable disease, cause of death, bioterrorism The emergence of ICD-10-CM brings anticipation about future uses, including the accurate capturing and reporting of public health diseases. Public health’s focus is on diagnosing the health concerns of entire communities and promoting healthy practices and behaviors to assure populations stay healthy. Many distinctions can be made between public health and clinical health. While public health focuses on many different clinical disciplines, its primary focus is on entire populations rather than individual patients.4 Therefore, for this research project, public health diseases include reportable diseases or the Center for Disease Control and Prevention (CDC) nationally notifiable infectious diseases, the National Vital Statistics Report of the top 10 leading causes of mortality, and ICD-9-CM supplemental classification for morbidity/mortality related to terrorism.5-7 A major issue that this research study hoped to address is whether ICD-10-CM is designed to capture public health diseases (as described above) more effectively, fully, and more clearly than ICD-9-CM. This is extremely important in this day of newly evolved diseases such as AIDS, SARS, and avian flu as well as acts of bioterrorism. It is expected that the ICD-10-CM system incorporates these newly found diseases and can easily adapt to ever changing public health conditions. However, this may not be the case. Thus, it is important to assess if the ICD-10-CM system is a more useful classification system than ICD-9-CM. The findings from this study will provide guidance to healthcare and pubic health stakeholders so that improvements to the ICD-10-CM system can be made and specific educational practices related to its implementation can be incorporated. With the awareness and adoption of these changes, the transition from the use of ICD-9-CM to ICD-10-CM will hopefully be smooth. The purpose of this study is threefold: - to investigate the completeness of the ICD-10-CM system in capturing public health diseases (reportable diseases, diseases related to the top 10 causes of death, and diseases related to terrorism) when compared to ICD-9-CM - to measure the effectiveness (intended result) of ICD-10-CM in capturing public health diseases when compared to ICD-9-CM - to collect feedback from users on how applicable the ICD-10-CM systems are in relation to capturing public health diseases Review of Literature According to the National Center for Health Statistics (NCHS) and the Centers for Medicare & Medicaid (CMS), the ICD-10-CM and ICD-10-PCS have many advantages over the ICD-9-CM coding system.8-9 Notable improvements in the content and format include: - the addition of information relevant to ambulatory and managed care encounters - expanded injury codes - the creation of combination diagnosis/symptom codes to reduce the number of codes needed to fully describe a condition - the addition of a sixth character (which allows for greater expansion and specificity) - incorporation of common fourth and fifth digit subclassifications - laterality (which allows for greater specificity regarding right and left side of body and specific body region) - greater specificity in code assignment - further expansion than was possible with ICD-9-CM - unique codes for all substantially different procedures - new procedures can be added as unique codes However, in the ICD-10-CM Field Testing Project summary report developed by the American Hospital Association (AHA) and AHIMA, even though ICD-10-CM was felt to be an improvement over ICD-9-CM by 76 percent of the participants, a total of 761 errors or conflicts in the instructions in ICD-10-CM were reported.10 After eliminating the duplications and other problems, a total of 305 issues remained. In the final list of identified problems, difficulty in locating a diagnostic term in the index was by far the most commonly reported problem. Also, 25 of the reported problems pertained to codes for external causes of morbidity—codes that could affect public health reporting because of the lack of specific causes for infectious disease as well as other causes of morbidity. Participants also reported the number of diagnostic statements that were unable to be coded in ICD-10-CM. They were unable to find an ICD-10-CM code for a total of 380 diagnoses. Upon review of the problem identification forms, the reasons why some of the diagnoses could not be coded were eliminated (due to duplication by more than one participant or misinterpretation of instructions etc.) and 151 diagnoses that could not be coded fell into the following categories: - Diagnosis was not indexed under the expected main terms or subterms - Insufficient documentation to assign a code (clarification with a physician would be necessary) - Error in index or tabular part of the coding system - Concept does not exist in ICD-10-CM - Code choices not applicable to diagnosis (i.e., either a clear “default” code that is broad enough to cover the diagnosis should be provided or additional codes should be made available) - Diagnosis is more specific than available code choices - Unclear instructions Also, the only index available at the time of the field testing project was in a format that was difficult to read, which made it difficult to readily locate some diagnostic terms, even though the terms were present. The reported problems have been submitted to NCHS for review and correction. Another area of concern is how well ICD-10-CM captures information related to the top 10 causes of death. According to the National Vital Statistics Report, the top 10 causes of death (an area of specific importance for public health) for 2002 were the following: - Diseases of the heart - Malignant neoplasms - Cerebrovascular diseases - Chronic lower respiratory diseases - Accidents (unintentional injuries) - Diabetes mellitus - Influenza and pneumonia - Alzheimer’s disease - Nephritis, nephritic syndrome and nephrosis These diagnoses accounted for 79 percent of all deaths occurring in the United States. Comments received from the ICD-10-CM Update: ICD-9-CM Coordination and Maintenance Meeting in November, 1999 for changes to ICD-10-CM were categorized according to the chapter and recommended disposition.12 Below, the authors have linked the comments related to changes to ICD-10-CM to the top 10 causes of death for 2002 as stated above. The number of comments that required further study is listed below in Table 1. It can be seen from Table 1 that 51 comments related to the top 10 causes of death, an area specifically related to public health, were viewed as needing further study. This also demonstrates that ICD-10-CM should be examined to see how well it accurately captures public health diseases — not only those that relate to mortality but other public health diseases such as nationally reportable diseases and diseases related to bioterrorism and so forth. To our knowledge, however, no studies have been conducted to determine if ICD-10-CM is effective in capturing public health diseases. Based on all of the above information, it is, therefore, important to determine if ICD-10-CM truly captures public health diseases. - Does the ICD-10-CM system fully capture public health diseases? - Does the ICD-10-CM system capture public health diseases more effectively than ICD-9-CM? - Does the ICD-10-CM system capture public health diseases straightforwardly and clearly (higher levels of agreement) than ICD-9-CM? Research Design and Procedures Part I: Public Health Disease Capture A descriptive research study was performed to investigate the completeness of the ICD-10-CM coding system in capturing public health diseases. First, the infectious and reportable public health conditions such as SARS, avian flu, smallpox, anthrax, and so forth were examined. This was done by reviewing each Web site for each state department of health to determine what diseases are required to be reported. Once this list was developed, it was supplemented with the CDC national reportable disease listing.13 The final list of public health reportable infectious diseases is listed in Table 2 and includes all the reportable infectious diseases by state as well as those required by CDC. Those that are required by CDC are displayed with an asterisk. This list was supplemented with two other areas that are very pertinent to public health—the top 10 causes of mortality and the classification of death and injury resulting from terrorism, a supplemental classification developed after September 11, 2001.14, 15 The top 10 causes of mortality included the following: accidents (20), Alzheimer’s disease (1), cerebrovascular disease (11), diabetes mellitus (4), influenza (5), lower respiratory disease (4), nephritis (14), septicemia (2), heart disease (summary-9), and the top five malignant neoplasms (5). The classification of death and injury resulting from terrorism list included 10 major categories such as terrorism involving explosion of marine weapons, destruction of aircraft, other explosions and fragments, fires, firearms, nuclear weapons, biological weapons, chemical weapons, terrorism other specified, and sequelae of terrorism. It is important to point out that each of the numbers listed relate to general categories of public health diseases. However, when coding the diseases, several more codes and descriptions were listed so that the number of codes far exceeds the 248 disease categories. A Web site was then developed so that all of the public health diseases and descriptions could be easily accessed by the researchers and the focus group members. For example, when organizing the reportable disease list on the Web site, we categorized every disease alphabetically and when the specific alphabetical category was accessed, it would immediately take the viewer to the list of reportable diseases. When the specific reportable disease was accessed, a spreadsheet with each of the ICD-9-CM and ICD-10-CM codes could be easily viewed. This was extremely useful for our focus group members when they reviewed the codes, rankings, explanations for using a specific ranking, and so forth. Although the list of 248 disease categories is not exhaustive of all public health diseases, it was believed that it did provide an adequate number to make comparisons between the two coding systems. The 248 public health diseases were then coded using both ICD-9-CM and ICD-10-CM so that comparisons between the two coding systems could be made. The June 2003 draft of ICD-10-CM and the 2006 version of ICD-9-CM were used for this study. The research coder for this study has a master’s of science degree in information science and is a Registered Health Information Administrator (RHIA) and has taught coding for more than 20 years. She was also trained and educated on the ICD-10-CM coding system through AHIMA’s online ICD-10-CM coding seminars. The research assistant, who performed data entry and assisted in some of the ICD-10-CM coding, has a master’s of science degree in health information systems and was also trained and educated on the ICD-10-CM coding system. All final codes were approved by our research coder. Quality checks for final codes were performed by our secondary investigator, who has a doctorate in public health and is an RHIA and certified coding specialist (CCS), and also by the principal investigator, who has a doctorate in epidemiology and is an RHIA. Comparison tables that describe the specificity of the coding for ICD-9-CM and ICD-10-CM for each of the public health diseases were developed. A ranked score was assigned to each public health disease for both the ICD-10-CM and ICD-9-CM coding systems. The ranking was determined by comparing the ICD-10-CM and ICD-9-CM systems for the number of codes, the level of specificity, and the ability of the code description to fully capture the diagnostic term. The ranked or ordinal scale consisted of the following: 5 = Diagnosis is fully captured by the code/codes (All codes, specificity, description is found) 4 = Diagnosis is almost fully captured by the code/codes (minor detail is missing) 3 = Diagnosis is partially captured by the code/codes (moderate detail is missing) 2 = Diagnosis is less than partially captured by the code/codes (major detail is missing) 1 = Diagnosis is not captured by the code/codes (Codes, specificity, description is not found) The ranking scale was developed by the research team and was reviewed and approved by the focus group members. All assigned rankings were reviewed and approved by the research team and by all focus group members. Researchers do acknowledge that there was some subjectivity involved in the assignment of the rankings. Once all rankings were assigned, a focus group was convened, which included seven experts in ICD-9-CM, ICD-10-CM, and public health. Two of the focus group members have medical degrees, two are working on their doctorates in public health and have extensive education and training in coding, and three have coding credentials and have worked in the coding field for more than 10 years. The purpose of the focus group was to review and examine the information accumulated from the study and to provide feedback and recommendations regarding where changes need to be made in the ICD-10-CM system. Therefore, the focus group examined the rankings and made changes. The researchers reviewed and discussed all comments from the focus group, clarifying any questions, and then made the appropriate changes to the rankings and code descriptions. Part II: Validation Study for Public Health Diagnoses The second part of the research study included using the ICD-10-CM Field Testing Project Study data from AHA and AHIMA to examine whether public health diagnoses are captured straightforwardly and clearly using ICD-10-CM. We obtained the validity study data from AHIMA and received permission to use the data in this study. The data included 359 patient cases in which as many as 10 narrative diagnoses were collected. As many as 10 ICD-10-CM codes by a coder and then by a validator were also included. Figure 1 shows one example of how the data was organized. Every diagnosis in the ICD-10-CM Field Testing Project Study database was examined and only those diagnoses that were related to public health and where there were differences between the coder and validator were extracted and recoded. Therefore, the cases that were examined were ones that were the most difficult to code. Diagnoses were considered related to public health either by being one of the top 10 diagnoses for morbidity, mortality, an infectious disease, disease related to terrorism, and so forth. The diagnoses were grouped into the same categories obtained for the first part of the study, i.e., top 10 diagnoses for mortality A category called “Other” was developed and it included those diagnoses that were considered public health related but did not fit into the categories related to the top 10 diagnoses for mortality. The cases were recoded by our coders to determine where differences may fall within the ICD-10-CM system. The same procedure was performed using ICD-9-CM in order to obtain a ranking for ICD-9-CM codes (see below) and therefore make objective comparisons between the two systems and to determine if ICD-10-CM is more capable in capturing public health diagnoses than ICD-9-CM. A total of 166 patient cases met the criteria for inclusion in our study and were reviewed and recoded. Levels of agreement between the coder and the validator were determined and a Kappa statistic was performed to determine if the differences between the coders were greater than what would be seen by chance. Therefore, the kappa statistic describes agreement achieved beyond chance, so the greater the kappa the greater the agreement between the coders. A nonparametric test, (Mann Whitney U test) was also performed to determine if the differences seen between the average kappa for both coding systems and the average ranking for both coding systems were statistically significant. A ranking scale based on the differences between the coder and validator for ICD-10-CM and ICD-9-CM was developed and is listed below: 5 = All digits are captured by codes assigned 4 = One digit is different between the codes assigned 3 = Two digits are different between the codes assigned 2 = Three digits are different between the codes assigned 1 = >3 digits are different between the codes assigned Part III: Statistical Analysis of the Data The qualitative data (or explanations regarding where the differences were found between the two coding systems) obtained from the first study was analyzed using qualitative themes. The explanations were categorized into five broad themes or areas such as those explained in the first ranking scale. For example, one of the public health reportable diagnoses is HIV and it was coded first in ICD-9-CM and then ICD-10-CM. Explanations regarding which coding system fully captured the disease and provided specific terms and codes related to the disease were developed. The explanations were categorized into one of the five areas explained in the first ranking scale. If it was found that a disease was only partially captured, further explanation was provided as to what should be included in order to fully capture the disease. Nonparametric statistics, (Mann Whitney U tests) were then computed on the rankings to determine if there were statistically significant differences between the two coding systems. For the second study, agreement levels between the coder and the validator were determined and a kappa statistic was performed to determine if the differences seen were statistically significant. Also, the Mann Whitney U test was used to determine if the differences seen between the mean rankings in coding agreement (based on the second ranking scale) and the mean kappa values for coding agreement between ICD-9-CM and ICD-10-CM were statistically significant. All of the statistical data, both qualitative and quantitative, was organized in tables for distribution and examination. Part IV: Focus Group Process A focus group was developed to review and examine the information accumulated from the study and provided feedback and recommendations on where changes needed to be made in the ICD-10-CM system. The focus group included experts in ICD-9-CM, ICD-10-CM and public health. Experts were defined as having 10 or more years experience in coding, public health, or both. Generally, the focus group members addressed the following questions: - After review of the reportable disease list, are there any diagnoses that you believe should be added, deleted, or changed? If so, please explain. - Do the explanations that relate to the coding of the reportable diseases, diseases related to the top 10 causes of death, and diseases related to terrorism provide enough information so that changes to the coding system can be made? If not, please specify which sections need further detail. - Do the ranked data and explanations related to differences in the I-10 and I-9 coding systems make sense? Do you need additional information to clarify any cases? If so, which ones? - Based on the information provided to you, what recommendations do you have to improve the ICD-10-CM coding system for public health reporting? Once all of the focus group responses were collected, changes were made by: - Adding more public health diseases that may have been missed. - Deleting some diseases that were inappropriate. - Changing some of the rankings based on additional information related to the coding specificity, descriptions, and explanations of coding rules and guidelines. - Adding information to the discussion section of this report related to recommendations needed to improve the ICD-10-CM coding system. This study was submitted to the University of Pittsburgh’s Institutional Review Board (IRB) and received approval at the exempt level. Overall results demonstrate that ICD-10-CM is more specific and fully captures more of the public health diseases than ICD-9-CM. In the analysis of all the public health diseases such as reportable diseases, top 10 causes of death, and those related to terrorism, it was found that the overall rankings for disease capture for ICD-10-CM were significantly higher than the rankings for ICD-9-CM (see Table 3). Furthermore, when we examined differences in disease capture by each system, several diseases were captured differently. Table 4 shows those differences for reportable diseases by rank as well as an explanation for where the differences occurred. It can be seen, again, that ICD-10-CM fully captured more of the reportable diseases than ICD-9-CM. However, some diseases were not fully captured by ICD-10-CM. Table 5 shows which diseases were not fully captured by ICD-10-CM as well as the rank received for each disease. It can be seen that several diseases are not captured at all by either system. These include: anaplasmosis, basidiobolomycosis, campylobacteriosis, emerging or exotic disease, Nipah virus, norovirus, and waterborne and all “other” outbreaks. Table 6 displays those reportable diseases that are ranked the same in ICD-9-CM and ICD-10-CM but do not fully capture the true description of the illness. When the top 10 causes of death were broken down by average rank for ICD-10-CM and ICD-9-CM, it showed that three categories; accidents, cerebrovascular disease, and nephritis showed very high significance between the coding systems, while influenza, septicemia, and the top five cancers did not. (See Table 7) Table 8, Table 9, Table 10, Table 11, and Table 12 break out the ranked differences for each of the top 10 diagnoses that are related to mortality, such as accidents, cerebrovascular disease, and so forth. These results demonstrate that ICD-10-CM fully captures more of the diseases related to mortality than ICD-9-CM. It can also be seen that ICD-10-CM provides more codes, specificity, categories, and explicit terminology than ICD-9-CM. There was only one disease, chronic renal failure, that was not fully captured by ICD-10-CM. However, chronic renal failure is no longer recognized in the clinical classification of chronic kidney disease and the clinical classification of chronic kidney disease has changed since the development of ICD-10-CM, so the decreased specificity in ICD-10-CM is related to changes in medicine since the development of ICD-10-CM rather than an intention to be less specific. It is also important to note that when examining asthma (see Table 12), the terminology between the two systems differs a great deal. This is because the terminology and code structure reflect the current clinical classification of asthma whereas the terminology and codes in ICD-9-CM do not. This has important implications for public health because if an individual is using ICD-9-CM codes to analyze treatment outcomes, prevalence of asthma in the population, and occurrences of acute episodes of asthma, they would not be examining the correct clinical categorization. Improvements in the ICD-10-CM coding system for diagnoses related to terrorism are needed (see Table 13). Even though the ICD-10-CM system captured more of the diagnoses than ICD-9-CM, the overall mean ranking for ICD-10-CM is 4.2, the lowest of any of the other categories reviewed. - specifying which type of weapon is used for each of the explosions; - specifying which type of biological, chemical, or nuclear weapon was used; - how the aircraft was destroyed; and - what caused the explosion or fire. If this information could be added to the description of the code, the ICD-10-CM system would fully capture the necessary information related to terrorism. Also, in order to continue to use syndromic surveillance techniques we need to insure that the symptom codes pertaining to syndromic surveillance are retained in ICD-10-CM when we change from ICD-9-CM. Part II: Results of Validation Study for Public Health Diseases Comparisons were made between ICD-9-CM and ICD-10-CM using the AHIMA and AHA Field Testing Project study data. Significant differences in coding between the coder and validator were found. The average ranking for ICD-9-CM, average percentage of agreement, and kappa values were higher than the average rank, average percentage of agreement and kappa values for ICD-10-CM (Table 14 and table 15). Statistically significant differences were found for external causes of injury, diabetes (average rank only), lower respiratory disease, heart disease, malignant neoplasms and other. This type of result is logical to anticipate because the coders in the study were more experienced with the ICD-9-CM system than the ICD-10-CM system due to the current use of ICD-9-CM in healthcare in the United States. However, it also demonstrates how coders may perform initially when using ICD-10-CM. In this study the coders were trained to use the ICD-10-CM system. The less than equal performance when using ICD-9-CM as compared to ICD-10-CM points to the potential need for more specific coding education and practice with the ICD-10-CM system in order to have accurate coding. Education and training should focus on the categories in which there were significant differences in the coding such as in external causes of injury and heart disease. Also, the tabular index of ICD-10-CM was found to be very cumbersome to navigate. However, ICD-10-CM is still, technically, a draft and has not been implemented yet and the implementation date is not yet known so the code books, encoding software, and other tools that coders typically use for ICD-9-CM coding purposes are not yet available for ICD-10-CM. Once these coding tools are available for ICD-10-CM, improvements in the navigation of the system will most likely improve. However, product development should aim to increase the accuracy of code assignment particularly in the areas (shown in Table 14 and Table 15) that have statistically significant differences. It was also important to determine what type of coding differences occurred between the coder and validator when using ICD-10-CM. Many differences were found and they are listed in Table 16 by public health category. It was found that use of the seventh character extension for initial encounter tended to cause differences between the research coder and the validator. Also, for codes less than six digits, a placeholder should be assigned, and this also caused differences. These are two new coding rules within ICD-10-CM and this could be why they frequently differed. Other differences include choosing a code that may be more or less specific than the validator. Within the external causes of injury category, specificity related to the cause of the injury led to differences as well as the deactivation of certain codes such as in the X50 area which were replaced by Y92-93 codes. Other differences were grouped into a category called “Variation in Code” simply because the two codes chosen did not match in relation to the disease description. Also, some differences occurred because an additional code was not included when needed or when an additional code was added when it was not necessary. As this study demonstrates, the use of ICD-10-CM has great implications for our entire nation since public health diseases, which include epidemics and other diseases related to bioterrorism, are generally able to be captured in a more specific way when using the ICD-10-CM system. This can be seen for all public health reportable diseases, diseases related to the top 10 causes of mortality, and diseases related to terrorism. Also, the differences found within this study were statistically significant for public health reportable diseases, accidents, cerebrovascular disease, diabetes mellitus, lower respiratory disease, nephritis, heart disease, and terrorism related diagnoses. However, there were some public health diseases that were not fully captured by ICD-10-CM. It was also found that some public health diseases were not captured at all by either system. It is recommended that NCHS evaluate those conditions that are less specific in ICD-10-CM and determine whether additional specificity should be added. However, the less specificity found in some ICD-10-CM codes may be intentional due to a valid reason. For example, perhaps the greater specificity found in ICD-9-CM was determined to no longer be clinically significant or represents outdated thinking such as chronic renal disease and asthma. Also, ICD-9-CM is updated annually, whereas the most recent version of ICD-10-CM available is from 2003. It is possible that some of the differences in specificity relate to changes that have been made to ICD-9-CM since ICD-10-CM was developed. It is assumed that whenever updates are made to ICD-9-CM that are not already reflected in ICD-10-CM, corresponding modifications will also be made to ICD-10-CM, but this will not be known for certain until a new version of ICD-10-CM is made available for use. When examining the differences in coding for the top 10 causes of mortality, it was found that ICD-10-CM fully captures more of the diagnoses related to mortality than ICD-9-CM. It can also be seen that ICD-10-CM provides more codes, specificity, categories, and explicit terminology than ICD-9-CM. Only one diagnosis, chronic renal failure, was not fully captured by ICD-10-CM. However, chronic renal failure is no longer recognized in the clinical classification of chronic kidney disease and the clinical classification of chronic kidney disease has changed since the development of ICD-10-CM, so the decreased specificity in ICD-10-CM is related to changes in medicine since the development of ICD-10-CM rather than an intention to be less specific. It is also important to note that when examining asthma, the terminology between the two systems differs a great deal. This is because the terminology and code structure reflect the current clinical classification of asthma whereas the terminology and codes in ICD-9-CM do not. This has important implications for public health because using ICD-9-CM codes to analyze treatment outcomes, prevalence of asthma in the population, and occurrences of acute episodes of asthma, would not provide the correct clinical categorization. Improvements to the ICD-10-CM coding system are needed for diagnoses related to terrorism. Necessary improvements include specifying which type of weapon is used for each of the explosions as well as which type of biological, chemical, or nuclear weapon was used, how the aircraft was destroyed, and what caused the particular explosion or fire.16 When comparing coder agreement from the AHA and AHIMA ICD-10-CM Field Testing Project study data cases, it was found that the ICD-9-CM had higher levels of agreement than ICD-10-CM. This finding was expected, because of the familiarity and extensive use of the ICD-9-CM system compared to ICD-10-CM, but is also important in that it provides insight regarding areas of focus for education. The areas that appear to need education may include external causes of injury, diabetes, lower respiratory disease, heart disease, and malignant neoplasms, since each of these categories showed statistically significant differences in coder agreement between ICD-10-CM and ICD-9-CM. Other areas needing educational attention include the use of the seventh character extension, use of a placeholder, use of additional codes, and overall use of greater specificity. However, it is also important to note that even though ICD-10-CM is more specific, it may be less useful if less reliable. The finding that ICD-9-CM has a higher kappa between coders may mean that while ICD-9-CM descriptors may seem less specific, there is strong agreement between coders. However, this finding may be present because coders within this study were more familiar and more educated on the ICD-9-CM coding system than the ICD-10-CM system. As with any research study there are always limitations. Some limitations to this study include: - Examining only a sample of public health diagnoses - Rankings for both coding systems for public health diseases, top 10 causes of mortality, and diseases related to terrorism may be subjective when assigned. - Missing some of the ICD-10-CM codes since the ICD-10-CM tabular list is very difficult to navigate and the latest version is from 2003. Also, there is a new draft version of ICD-10-CM, which should be made available soon, and some of the improvements discussed here have been incorporated into this new version. Changes mentioned above regarding chronic kidney disease, for example, have been incorporated into the new draft as well as additional changes to influenza including avian flu and so forth. This study can help to further refine the next draft of ICD-10-CM since it provides needed guidance regarding which specific disease codes are lacking in the ICD-10-CM coding system. However, further research should be done to examine the ICD-10-CM system’s new draft in relation to public health disease capture. Also, future research should focus on the influence ICD-10-CM will have on other important healthcare areas such as its effectiveness with SNOMED, its use with the Electronic Health Record (EHR), its implications for consumers who use a Personal Health Record (PHR), as well as its effect on quality improvement, clinical outcomes, and research effectiveness. The findings and recommendations in this study will provide guidance to healthcare and public health stakeholders so that improvements to the coding system and education related to its implementation can be addressed. These changes will facilitate a smooth transition from the use of ICD-9-CM to ICD-10-CM. Valerie J.M. Watzlaf, PhD, RHIA, FAHIMA, is an associate professor of health information management in the School of Health and Rehabilitation Sciences at the University of Pittsburgh in Pittsburgh, PA. Jennifer Hornung Garvin, PhD, RHIA, CPHQ, CCS, CTR, FAHIMA, is a medical informatics postdoctoral fellow at the Center for Health Equity Research and Promotion at the Philadelphia Veterans Administration Medical Center in Philadelphia, PA. Sohrab Moeini, BSIS, MS HIS, is a business analyst at the University of Pittsburgh Medical Center (UPMC) in Pittsburgh, PA. Patricia Anania-Firouzan, MSIS, RHIA, is an assistant professor of health information management in the School of Health and Rehabilitation Sciences at the University of Pittsburgh in Pittsburgh, PA. We would like to acknowledge the members of the focus group who provided pertinent feedback and information vital to this report. Focus group members include Sue Bowman, RHIA, CCS; Susan H. Fenton, PhD candidate, RHIA; Pat S. Wilson, RT (R), CPC, PMP; Mark Weiner, MD; Darren Linkin, MD, MSCE; Mary Stanfill, RHIA, CCS, CCS-P; and Mary F. Johnson, RHIT, CCS-P. This study was funded by the AHIMA/FORE Foundation Grant-in-Aid Program. 1. Department of Health and Human Services, Centers for Disease Control and Prevention, National Notifiable Disease Surveillance System (NNDSS). “Nationally Notifiable Infectious Diseases, United States 2005.” Available at http://www.cdc.gov/epo/dphsi/phs/infdis2005.htm, accessed September 21, 2005. 2. Anderson, R. and B. Smith. Division of Vital Statistics. National Vital Statistics Report. “Deaths: Leading Causes for 2002.” 53 no. 17 (March 7, 2005). Available at http://origin cdc.gov/nchs/data/nvsr/nvsr53/nvsr53_17.pdf accessed September 19, 2005. 3. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics. Classification of Diseases and Functioning and Disability. “Appendix I, Classification for Mortality/Morbidity, Terrorism.” Available at http://www.cdc.gov/nchs/about/otheract/icd9/appendix1.htm. 4. “Definition of Public Health.” 1996-2007 MedicineNet, Inc. Available at http://www.medterms.com/script/main/art.asp?articlekey=5120 5. Department of Health and Human Services, Centers for Disease Control and Prevention, National Notifiable Disease Surveillance System (NNDSS). “Nationally Notifiable Infectious Diseases, United States 2005.” 6. Anderson, R. and B. Smith. Division of Vital Statistics. National Vital Statistics Report. “Deaths: Leading Causes for 2002.” 7. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics. Classification of Diseases and Functioning and Disability. “Appendix I, Classification for Mortality/Morbidity, Terrorism.” 8. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics. Classification of Diseases and Functioning and Disability. “About the International Classification of Diseases, Tenth Revision,,Clinical Modification.” Available at http://www.cdc.gov/nchs/about/otheract/icd9/abticd10.htm. 9. Averill, R., Mullin, R., Steinbeck, B., Goldfield, N.,Grant, T., Butler, R., Development of the ICD-10 Procedure Coding System (ICD-10-PCS), under contract from CMS to 3M HIS Research. Available at http://www.cms.hhs.gov/ICD9ProviderDiagnosticCodes/Downloads/pcs2007.introduction. 10. AHA and AHIMA. “ICD-10-CM Field Testing Project Summary Report,” September 23, 2003. pp. 26-30. 11. Centers for Disease Control and Prevention. National Vital Statistics Report. “Deaths: Leading Causes for 2002.” 53 no. 17 (March 7, 2005): 1. 12. “ICD-10-CM Update.” From the ICD-9-CM Coordination and Maintenance Meeting, Baltimore, Maryland. November 2, 1999. 13. Department of Health and Human Services, Centers for Disease Control and Prevention, National Notifiable Disease Surveillance System (NNDSS). “Nationally Notifiable Infectious Diseases, United States 2005.” 14. Anderson, R. and B. Smith. Division of Vital Statistics. National Vital Statistics Report. “Deaths: Leading Causes for 2002.” 15. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics. Classification of Diseases and Functioning and Disability. “Appendix I, Classification for Mortality/Morbidity, Terrorism.” Article citation: Perspectives in Health Information Management 4;6, Summer 2007	4	28	0	0	0	1	0.781545	1	8,670
Mast cell activation syndrome Mast cell activation syndrome (MCAS) is one type of mast cell activation disorder (MCAD), and is an immunological condition in which mast cells inappropriately and excessively release chemical mediators, resulting in a range of chronic symptoms, sometimes including anaphylaxis or near-anaphylaxis attacks. Primary symptoms include cardiovascular, dermatological, gastrointestinal, neurological and respiratory problems. Unlike mastocytosis, another type of MCAD, where patients have an abnormally increased number of mast cells, patients with MCAS have a normal number of mast cells that do not function properly and are defined as "hyperresponsive". MCAS is still a poorly understood condition and is a current topic of research. Signs and symptomsEdit MCAS is a condition that affects multiple systems, generally in an inflammatory manner. Symptoms typically wax and wane over time, varying in severity and duration. Many signs and symptoms are the same as those for mastocytosis, because both conditions result in too many mediators released by mast cells. It has many overlapping characteristics with recurrent idiopathic anaphylaxis, although there are distinguishing symptoms, specifically hives and angioedema. - easy bruising - either a reddish or a pale complexion - burning feeling - diarrhea and/or constipation, cramping, intestinal discomfort - nausea, vomiting - swallowing difficulty, throat tightness - interstitial cystitis; burning in the bladder and urinary tract - Psychiatric & Neurological - brain fog, short term memory dysfunction, difficulty with recalling words - headaches, migraines - co-morbid psychiatric and behavioral symptoms as a result of mast cell mediators being released in the brain (i.e.: anxiety, depression, mood swings, etc.) - ocular discomfort, conjunctivitis - general fatigue and malaise - food, drug, and chemical allergies or intolerances (especially fragrances) - Cold and Heat Intolerance - Anaphylaxis If too many mediators are split into a patient's system, they may also experience anaphylaxis, which primarily includes: difficulty breathing, itchy hives, flushing or pale skin, feeling of warmth, weak and rapid pulse, nausea, vomiting, diarrhea, dizziness and fainting. Symptoms can be caused or worsened by triggers, which vary widely and are patient-specific. Common triggers include: - specific foods and drinks (especially alcohol, high-histamine content foods, and histamine releasing additives such as sulfites) - temperature extremes - airborne smells including perfumes or smoke - exercise or exertion - emotional stress - hormonal changes, particularly during adolescence, pregnancy and menstruation. There are no known causes, but the condition appears to be inherited in some patients. Symptoms of MCAS are caused by excessive chemical mediators inappropriately released by mast cells. Mediators include leukotrienes, histamines, prostaglandin, and tryptase. The condition may be mild until exacerbated by stressful life events, or symptoms may develop and slowly trend worse with time. MCAS is often difficult to identify due to the heterogeneity of symptoms and the "lack of flagrant acute presentation." The condition can also be difficult to diagnose, especially since many of the numerous symptoms are non-specific in nature. Mast cell activation was assigned an ICD 10 code (D89.40, along with subtype codes D89.41-43 and D89.49) in October 2016. - "Although different diagnostic criteria are published, a commonly used strategy to diagnose patients is to use all three of the following: - Symptoms consistent with chronic/recurrent mast cell release: Recurrent abdominal pain, diarrhea, flushing, itching, nasal congestion, coughing, chest tightness, wheezing, lightheadedness (usually a combination of some of these symptoms is present) - Laboratory evidence of mast cell mediator (elevated serum tryptase, N-methyl histamine, prostaglandin D2 or 11-beta- prostaglandin F2 alpha, leukotriene E4 and others) - Improvement in symptoms with the use of medications that block or treat elevations in these mediators" The World Health Organization has not published diagnostic criteria. Common pharmacological treatments include: - Mast cell stabilizers, including cromolyn sodium and natural stabilizers such as quercetin - H1-antihistamines, such as cetirizine or ketotifen or fexofenadine or loratadine - H2-antihistamines, such as ranitidine or famotidine - Antileukotrienes, such as montelukast or zileuton as well as natural products (e.g., curcumin or St. John's wort extracts) - Nonsteroidal anti-inflammatory drugs, including aspirin can be very helpful in reducing inflammation in some patients, while others can have dangerous reactions Fillers, binders and dyes in many medications are often the culprit in causing reactions, not necessarily the active agent, so alternative formulations and compounding pharmacies should be considered. Lifestyle changes may also be needed. Avoidance of triggers is important. It should be emphasized that MCAS patients can potentially react to any new exposure, including food, drink, medication, microbes and smoke via inhalation, ingestion or touch. A low histamine diet and other elimination diets can be useful in identifying foods that trigger or worsen symptoms. Many MCAS patients already have high histamine levels, so ingesting foods with high histamine or histamine liberators can worsen many symptoms such as vasodilation that causes faintness and palpitations. There is no cure for MCAS. For most, symptoms wax and wane, but many can experience a general worsening trend over time. Lifespan for those with MCAS appears to be normal, but quality of life can range from mild discomfort to severely impaired. Some patients are impaired enough to be disabled and unable to work. MCAS is a relatively new diagnosis, being unnamed until 2007, and is believed to be under-diagnosed. (Dr. Lawrence Afrin describes it as "likely quite prevalent" and having "increasingly apparent prevalence"). It has been suggested in the literature for decades; however diagnostic criteria have been proposed only in 2010. The condition was hypothesized by the pharmacologists John Oates and Jack Roberts of Vanderbilt University in 1991, and following a build-up of evidence featured in papers by Sonneck et al. and Akin et al., finally named in 2007. - Valent P (2013). "Mast Cell Activation Syndromes: Definition and Classification". Allergy. 68 (4): 417–24. doi:10.1111/all.12126. PMID 23409940. - Akin C, Valent P, Metcalfe DD (2010). "Mast cell activation syndrome: Proposed diagnostic criteria". J. Allergy Clin. Immunol. 126 (6): 1099–104.e4. doi:10.1016/j.jaci.2010.08.035. PMC 3753019. PMID 21035176. - Akin C (2015). "Mast Cell Activation Syndromes Presenting as Anaphylaxis". Immunology and Allergy Clinics of North America. 35 (2): 277–85. doi:10.1016/j.iac.2015.01.010. PMID 25841551. - White, Andrew, Dr. "A Tale of Two Syndromes – POTS and MCAS". The Dysautonomia Dispatch. Dysautonomia International, 17 Feb. 2015. Web. 12 Oct. 2015, at dysautonomiainternational.org. - Milner, Joshua, Dr. "Research Update: POTS, EDS, MCAS Genetics." 2015 Dysautonomia International Conference & CME. Washington DC. Dysautonomia International Research Update: POTS, EDS, MCAS Genetics. Web, at vimeo.com - Afrin, Lawrence B. "A Concise, Practical Guide to Diagnostic Assessment for Mast Cell Activation Disease." WJH World Journal of Hematology 3.1 (2014): 155-232. Accessed 29 January 2018 - Frieri M (2015). "Mast Cell Activation Syndrome". Clin Rev Allergy Immunol. 54 (3): 353–365. doi:10.1007/s12016-015-8487-6. PMID 25944644. - Afrin, Lawrence, Dr. "Presentation, Diagnosis, and Management of Mast Cell Activation Syndrome." Mast Cells: Phenotypic Features, Biological Functions and Role in Immunity. Nova Science, 2013. 155-232. - Ellis AK, Keith PK "Nonallergic rhinitis with eosinophilia syndrome" Curr Allergy Asthma Rep. Accessed 26 Feb 2018 - Finn DF, Walsh JJ (2013). "Twenty-first century mast cell stabilizers". Br. J. Pharmacol. 170 (1): 23–37. doi:10.1111/bph.12138. PMC 3764846. PMID 23441583. A diverse range of mast cell stabilizing compounds have been identified in the last decade from; natural, biological and synthetic sources to drugs already in clinical uses for other indications. Although in many cases, the precise mode of action of these molecules is unclear, all of these substances have demonstrated mast cell stabilization activity and therefore may have potential therapeutic use in the treatment of allergic and related diseases where mast cells are intrinsically involved.Table 1: Naturally occurring mast cell stabilizers - Weng Z, Zhang B, Asadi S, Sismanopoulos N, Butcher A, Fu X, Katsarou-Katsari A, Antoniou C, Theoharides TC (2012). "Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans". PLoS ONE. 7 (3): e33805. Bibcode:2012PLoSO...733805W. doi:10.1371/journal.pone.0033805. PMC 3314669. PMID 22470478. - Sonneck K, Florian S, Müllauer L, Wimazal F, Födinger M, Sperr WR, Valent P. "Diagnostic and subdiagnostic accumulation of mast cells in the bone marrow of patients with anaphylaxis: Monoclonal mast cell activation syndrome." Int Arch Allergy Immunol. 2007;142(2):158-64. Epub 2006 Oct 20. - Akin C, Scott LM, Kocabas CN, Kushnir-Sukhov N, Brittain E, Noel P, Metcalfe DD. "Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with "idiopathic" anaphylaxis." Blood. 2007 Oct 1;110(7):2331-3. Epub 2007 Jul 16. - Characterization of Mast Cell Activation Syndrome - 2016 Lawrence Afrin, M.D et al. - The role of mast cells in functional GI disorders FFT at Gut/BMJ - Mast Cell Activation Syndrome – May 2015 - Spectrum of mast cell activation disorders – 2014 - Mast cell activation syndromes: definition and classification – 2013 - Expanding Spectrum of Mast Cell Activation Disorders: Monoclonal and Idiopathic Mast Cell Activation Syndromes – 2013	2	16	2	0	0	2	0.877403	4	2,451
HCPCS and ICD and CPT … Oh My! Let’s get the acronyms out of the way first: ICD: International Statistical Classification of Disease and Related Health Problems CPT: Current Procedural Terminology HCPCS: Healthcare Common Procedures Coding System Second, why do these medical codes exist in the first place? It’s primarily about getting reimbursement for the approximately 5 billion transactions of services and products in the healthcare universe each year. There are other reasons, though, as well, including: - Outcome measurements - Clinical, financial and administrative performance measurement - The design of payment systems and claims processing - Reporting on new medical technology - Improving reimbursement systems - Care and disease process management So even if you’re not a medical billing expert, knowing a bit about this subject is valuable. So here, then, is a teeny-tiny bit. ICD is comprised of two parts, Clinical Modification, used for diagnostic coding of diseases and medical conditions (there are about 68,000 codes for this) and Procedure Coding System, for inpatient hospital procedures (about 87,000 codes). The World Health Organization manages these and they date back to 1893. ICD Code example: Format: 3–7 characters long (first is alpha, second is numeric, third through seventh are alpha or numeric, anything after the third character has a decimal point) I25.110 = “Atherosclerotic heart disease of native coronary artery with unstable angina pectoris” CPT is a uniform coding system consisting of descriptive terms and identifying codes that are used primarily to identify medical services and procedures furnished by physicians and other healthcare professionals. The American Medical Association owns the trademark and manages CPT. It’s been around since 1979. CPT Code example: Format: Five characters, either numeric or alpha 22222 = “Osteotomy Procedures on the Spine” There are three categories for CPT: CPT I – used for reporting claims and getting paid. CPT II – used to track additional services attached to a healthcare visit. These codes are not payable and are for statistical use. CPT III – These are fairly new to the healthcare industry and are reported to help health facilities and government agencies track the efficacy of new, emergent medical techniques. HCPCS codes are intended to be a uniform way of classifying similar durable medical equipment, prosthetics, and orthotics. HCPCS was created in 1978 and up until 1996 its use was voluntary. The U.S. Government Centers for Medicare and Medicaid Services (CMS) manages HCPCS. HCPCS Code example: Format: Five characters, the first is alpha, the remaining four are numeric. A4351 = “Intermittent urinary catheter; straight tip, with or without coating (teflon, silicone, silicone elastomer, or hydrophilic, etc.), each” (this one’s our favorite!) HCPCS has two classifications: HCPCS Level I (which, confusingly, is the same thing as CPT I) and HCPCS Level II. HCPCS Level II is designed to represent non-physician services like ambulance rides, wheelchairs, walkers, and other durable medical equipment. Here’s a list of the major categories of HCPCS codes: A codes: transportation, medical and surgical supplies, miscellaneous and experimental B codes: enteral and parenteral therapy C codes: temporary hospital OPPS D codes: dental-related codes E codes: durable medical equipment G codes: temporary procedures and professional services H codes: behavioral health/substance abuse services J codes: drugs administered other than oral method, chemotherapy drugs K codes: temporary codes for durable medical equipment regional carriers L codes: orthotic/prosthetic procedures M codes: other medical services P codes: pathology and laboratory Q codes: temporary codes (limited use and guidelines specific) R codes: diagnostic radiology services S codes: temporary national codes (non-Medicare) codes T codes: temporary state Medicaid agency codes V codes: vision/hearing services If you have gotten this far, you’re pretty much an expert on medical coding. So, congratulations! Here are a few additional references	4	4	2	0	2	2	0.513495	6	925
In general, the standard physical exam typically includes: Vital signs: blood pressure, breathing rate, pulse rate, temperature, height, and weight. Vision acuity: testing the sharpness or clarity of vision from a distance. Head, eyes, ears, nose and throat exam: inspection, palpation, and testing, as appropriate. What tests should be done during a physical? - Medical history. Your doctor will ask you questions about your lifestyle and habits, including smoking and drinking. - Vital signs. - Heart and lung exams. - Head, neck, and abdominal exams. - Neurological exam. - Skin exam. - Laboratory work. What are 2 things the doctor checks during a routine physical exam? Your doctor will do a blood pressure reading, check your heart rate, take your body temperature, and may review your respiratory rate. After a check of your vital signs, a doctor will usually review your appearance for indications of any abnormalities or potential issues. What happens at a physical for a girl? It includes a routine check of vitals like blood pressure, heart rate, respiration, and temperature. Your doctor may also examine your abdomen, extremities, and skin for any signs of health changes. What should you not do before a physical exam? - 1) Get a good night’s sleep. Try to get eight hours the night before your exam so your blood pressure is as low as possible. - 2) Avoid salty or fatty foods. - 3) Avoid exercise. - 4) Don’t drink coffee or any caffeinated products. - 5) Fast. - 6) Drink water. - 7) Know your meds. What blood tests are run during a physical? To complete the physical, your doctor may draw blood for several laboratory tests. These can include a complete blood count and a complete metabolic panel (also called a chemistry panel). The panel tests your blood plasma and can indicate any issues that exist in your kidneys, liver, blood chemistry, and immune system. How long is a physical good for? Q: How long is a physical valid? A: According to the State, physicals are valid for 365 days (one year from date of actual exam). What would show up in a blood test? Blood tests can be used for many different things, including to check cholesterol and blood glucose levels. These help monitor your risk of heart and circulatory diseases and diabetes, or how your condition is being managed. Tests for different chemicals and proteins can indicate how your liver or kidneys are working. Do I have to take my clothes off for a physical? For annual physicals, patients will be gowned, so they shouldn’t wear constricting, hard-to-remove clothing. What age do doctors check your private parts? Doctors recommend yearly checkups that focus on the female reproductive system, starting between the ages of 13 and 15. Often called well-woman visits, they can catch small issues before they become big ones. Is a Pap smear included in a physical? The patient preventive medicine services codes 99381-99397 include an age- and gender-appropriate physical exam. According to CPT Assistant, performing a pelvic and breast exam, as well as obtaining a screening Pap smear, are all part of the comprehensive preventive service and should not be reported separately. Can I drink water before my physical? If your health care provider has told you to fast before a blood test, it means you should not eat or drink anything, except water, for several hours before your test. When you eat and drink normally, those foods and beverages are absorbed into your bloodstream. How long do you fast for a physical? How long do I have to fast before having a physical exam? Because we typically take blood to check your cholesterol, we ask that you fast for about 8 hours before a morning appointment. If you have an afternoon appointment, there’s no need to fast, but just have a light meal that morning. Can I drink water before body check up? Do not eat or drink at least 8 – 10 hours prior to the check-up. Water, however may be freely taken to avoid dehydration effects on blood sugar and cholesterol tests in the program. Please do not drink alcohol for at least 24 hours prior to appointment as drugs and alcohol may affect some tests. How often should you get a physical? In general, healthy people should get a physical every two to three years in their 20s, every other year in their 30s and 40s, and annually starting around age 50. You should also get regular health screenings like skin checks, pap smears, mammograms, and colorectal cancer screening. What are the 6 components of a physical exam? - Inspection. Is the intial part of the exam. - Palpation. Examination by roughing with the fingers or hands. ( - Percussion. Producing sounds by tapping various parts of the body. - Auscultation. Listening to sounds made by patient body , indirectly with stethoscope. How much is a physical? Without insurance, the average cost of a physical exam ranges from $50 to $200. If you need a physical exam but don’t have insurance, Mira can help you out. Physicals can often be done at urgent care centers, and for $45/month, you can get up-front copays at an urgent care center near you. Does a physical include a urine test? A routine urinalysis can tell your doctor a great deal. Diabetes, urinary tract infections, and kidney problems are among the many medical conditions that can be detected by routine urinalysis results. Very often, a routine urinalysis is part of a general physical exam. Are annual physicals really necessary? It is important to have a regular doctor who helps make sure you receive the medical care that is best for your individual needs. But healthy people often don’t need annual physicals, and they can even do more harm than good. Here’s why: Annual physicals usually don’t make you healthier. Does annual physical include urine test? A urinalysis is a lab test that is often part of your annual physical with your Riverside Health System primary care provider. What do you do at a physical? - The doctor will ask many questions. - Vital signs are checked. - Evaluating your physical appearance. - Check the muscles and organs. - Look over your head and neck. - Samples might be taken and sent to a lab. - Male Physical Exam. - Female Physical Exam. What happens at a physical for a man? In This Article: At most physicals, doctors will screen your blood pressure, heart rate, temperature, lungs and head, as well as check your general appearance. Males, specifically, should expect a testicular exam, a hernia exam, a penis exam and a prostate exam. What is the difference between a physical and wellness exam? A physical exam helps your doctor figure out what the problem is and what needs to be done. When you’re healthy and feeling good, you want to stay that way. A wellness exam helps your doctor understand what’s working for you and how to best support your continued health and well-being. What are the 5 main blood tests? - Complete blood count (CBC). - Basic metabolic panel. - Blood enzyme tests. - Blood tests to check for heart disease. - Blood clotting tests, also known as a coagulation panel. Would a full blood count show anything serious? Full blood count (FBC) This can help give an indication of your general health, as well as provide important clues about certain health problems you may have. For example, an FBC may detect signs of: iron deficiency anaemia or vitamin B12 deficiency anaemia. infection or inflammation.	3	8	2	0	0	1	0.98634	3	1,655
What is ICD-10 Codes, Importance and Benefits ICD-10 codes (The tenth edition of International Classification of Diseases) is a clinical cataloging program that came into force on October 1, 2015. The transition of ICD-10 codes for medical billing from ICD-9 codes took place after a series of chronic delays. However, “ICD-10” offers wider classification options than its predecessor “ICD-9”. This program is adopted by the federal government or regulation entities while it is owned, maintained and published by The World Health Organization (WHO). ICD-10 codes can have 2-7 characters each representing a specific diagnosis. These 7 characters represent section, body system, root operation, body region, approach, method, and qualifier respectively. First three characters are designated as categories of the codes and can be expanded to four, five, six or seven in order to add more specific information. Let’s take an example of ICD-10 codes of medical billing i.e. S86, in this instance, “S” used along with numerals “8” and “6” refers to the category of the diagnosis related to injury of muscle, fascia, and tendon at lower leg level. This three-character category of ICD-10 data can stand alone as a code. Why is ICD 10 important: It is essential for physicians as well as their faculty that ICD-10 codes of medical billing are not just limited to compliance, but it is more about improving the patient outcomes. The clinical details in the latest version provide the physicians with more information they require to measure healthcare service quality and improve the care of individuals. Physicians would be glad to know that enhanced reporting capabilities of ICD-10 allow high reimbursements and increased pay for performance which directly factors in improvement of operational costs and the financial process. Moreover, it has potential to improve the following: - Outcome measurements - Clinical, financial and administrative performance measurement - The design of payment methods and claims processing - Reporting on new medical technology - Improving reimbursement systems - Care and disease process management Benefits of ICD-10 Codes of Medical Billing: Most of the physicians have successfully adapted to this new transition, but still, there are a few who are confused whether to comply or not. If you are one of the latter, then read the following benefits of ICD-10 to get rid of your uncertainty. - Lesser Fraudulent: Implementation of ICD-10 codes of medical billing results in lesser frauds and more claims, which escalates the cost of healthcare provider’s and payer’s premiums. This new transition ultimately improves the patient care and helps to obtain more reimbursement for the physicians. - Performance Analyzing: This upgraded version can help the provider to analyze their services, utilization of resources, operational costs and outcomes. More the detail on procedure types, more it will be easier for the physicians to monitor their own performance which will allow them to take essential steps to make headway. - Enhanced Quality of Documentation: The ICD-10 codes of medical billing utterly fall back on the clinical documentation. There are about 68000 codes added to the new ICD-10 codes and the accuracy of codes rely on clinical documentation. So, with the adoption of the ICD-10 coding system, quality of documentation will also be enhanced. - Fair Pay: This granular ICD-10 system allows the physicians to appropriately document the intricacy of the care rendered and differentiate between long-standing patients and patients who visit for regular check-ups. In this way, the patients can be billed in accordance with service provided which result in better payment procedures. - Build Relationship: The new ICD-10 codes of medical billing help the physicians to build or improve their relationships with patients and insurance carrier. Moreover, the physicians can shake hands with the third-party agencies in order to increase the reimbursement, thereby enhancing their revenue and financial process. With over 13 years of industry experience, Bikham Healthcare offers you top of the line medical billing and coding services with a team that houses complete knowledge of ICD-10 codes in order to help achieve your financial objectives with minimum denials and no delays.	4	4	2	0	0	2	0.63435	4	893
Mania, also known as manic syndrome, is a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together with lability of affect." Although mania is often conceived as a "mirror image" to depression, the heightened mood can be either euphoric or irritable; indeed, as the mania intensifies, irritability can be more pronounced and result in violence, or anxiety. \|Other names\|\|Manic syndrome, manic episode\| \|Graphical representation of mania and hypomania\| The symptoms of mania include heightened mood (either euphoric or irritable); flight of ideas and pressure of speech; and increased energy, decreased need for sleep, and hyperactivity. They are most plainly evident in fully developed hypomanic states; in full-blown mania, however, they undergo progressively severe exacerbations and become more and more obscured by other signs and symptoms, such as delusions and fragmentation of behavior. Mania is a syndrome with multiple causes. Although the vast majority of cases occur in the context of bipolar disorder, it is a key component of other psychiatric disorders (such as schizoaffective disorder, bipolar type) and may also occur secondary to various general medical conditions, such as multiple sclerosis; certain medications may perpetuate a manic state, for example prednisone; or substances of abuse, such as caffeine, cocaine or anabolic steroids. In the current DSM-5, hypomanic episodes are separated from the more severe full manic episodes, which, in turn, are characterized as either mild, moderate, or severe, with specifiers in regard to certain symptomatic features (e.g. catatonia, psychosis). Mania is divided into three stages: hypomania, or stage I; acute mania, or stage II; and delirious mania (delirium), or stage III. This "staging" of a manic episode is very useful from a descriptive and differential diagnostic point of view. Mania varies in intensity, from mild mania (hypomania) to delirious mania, marked by such symptoms as disorientation, florid psychosis, incoherence, and catatonia. Standardized tools such as Altman Self-Rating Mania Scale and Young Mania Rating Scale can be used to measure severity of manic episodes. Because mania and hypomania have also long been associated with creativity and artistic talent, it is not always the case that the clearly manic bipolar person needs or wants medical help; such persons often either retain sufficient self-control to function normally or are unaware that they have "gone manic" severely enough to be committed or to commit themselves. Manic persons often can be mistaken for being under the influence of drugs. In a mixed affective state, the individual, though meeting the general criteria for a hypomanic (discussed below) or manic episode, experiences three or more concurrent depressive symptoms. This has caused some speculation, among clinicians, that mania and depression, rather than constituting "true" polar opposites, are, rather, two independent axes in a unipolar—bipolar spectrum. A mixed affective state, especially with prominent manic symptoms, places the patient at a greater risk for completed suicide. Depression on its own is a risk factor but, when coupled with an increase in energy and goal-directed activity, the patient is far more likely to act with violence on suicidal impulses. Hypomania, which means "less than mania", is a lowered state of mania that does little to impair function or decrease quality of life. It may, in fact, increase productivity and creativity. In hypomania, there is less need for sleep and both goal-motivated behaviour and metabolism increase. Some studies exploring brain metabolism in subjects with hypomania, however, did not find any conclusive link as there are those that reported abnormalities while some failed to detect differences. Though the elevated mood and energy level typical of hypomania could be seen as a benefit, mania itself generally has many undesirable consequences including suicidal tendencies, and hypomania can, if the prominent mood is irritable rather than euphoric, be a rather unpleasant experience. In addition, the exaggerated case of hypomania can lead to problems. For instance, positivity for a person could make him engaging and outgoing, having a positive outlook in life. When exaggerated in hypomania, such person can display excessive optimism, grandiosity, and poor decision making, often without regard to the consequences. A single manic episode, in the absence of secondary causes, (i.e., substance use disorder, pharmacologic, general medical condition) is sufficient to diagnose bipolar I disorder. Hypomania may be indicative of bipolar II disorder. Manic episodes are often complicated by delusions and/or hallucinations; should the psychotic features persist for a duration significantly longer than the episode of mania (two weeks or more), a diagnosis of schizoaffective disorder is more appropriate. Certain "obsessive-compulsive spectrum" disorders as well as impulse control disorders share the name "mania," namely, kleptomania, pyromania, and trichotillomania. Despite the unfortunate association implied by the name, however, no connection exists between mania or bipolar disorder and these disorders. B12 deficiency can also cause symptoms characteristic of mania and psychosis. Hyperthyroidism can produce similar symptoms to those of mania, such as agitation, elevated mood, increased energy, hyperactivity, sleep disturbances and sometimes, especially in severe cases, psychosis. Signs and symptomsEdit A manic episode is defined in the American Psychiatric Association's diagnostic manual as a "distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalization is necessary)," where the mood is not caused by drugs/medication or a medical illness (e.g., hyperthyroidism), and (a) is causing obvious difficulties at work or in social relationships and activities, or (b) requires admission to hospital to protect the person or others, or (c) the person is suffering psychosis. To be classed as a manic episode, while the disturbed mood and an increase in goal directed activity or energy is present at least three (or four if only irritability is present) of the following must have been consistently present: - Inflated self-esteem or grandiosity. - Decreased need for sleep (e.g., feels rested after 3 hours of sleep). - More talkative than usual or pressure to keep talking. - Flights of ideas or subjective experience that thoughts are racing. - Increase in goal directed activity, or psychomotor acceleration. - Distractibility (too easily drawn to unimportant or irrelevant external stimuli). - Excessive involvement in activities with a high likelihood of painful consequences.(e.g., extravagant shopping, improbable commercial schemes, hypersexuality). Though the activities one participates in while in a manic state are not always negative, those with the potential to have negative outcomes are far more likely. The World Health Organization's classification system defines a manic episode as one where mood is higher than the person's situation warrants and may vary from relaxed high spirits to barely controllable exuberance, accompanied by hyperactivity, a compulsion to speak, a reduced sleep requirement, difficulty sustaining attention and often increased distractibility. Frequently, confidence and self-esteem are excessively enlarged, and grand, extravagant ideas are expressed. Behavior that is out of character and risky, foolish or inappropriate may result from a loss of normal social restraint. Some people also have physical symptoms, such as sweating, pacing, and weight loss. In full-blown mania, often the manic person will feel as though his or her goal(s) trump all else, that there are no consequences or that negative consequences would be minimal, and that they need not exercise restraint in the pursuit of what they are after. Hypomania is different, as it may cause little or no impairment in function. The hypomanic person's connection with the external world, and its standards of interaction, remain intact, although intensity of moods is heightened. But those who suffer from prolonged unresolved hypomania do run the risk of developing full mania, and indeed may cross that "line" without even realizing they have done so. One of the signature symptoms of mania (and to a lesser extent, hypomania) is what many have described as racing thoughts. These are usually instances in which the manic person is excessively distracted by objectively unimportant stimuli. This experience creates an absent-mindedness where the manic individual's thoughts totally preoccupy him or her, making him or her unable to keep track of time, or be aware of anything besides the flow of thoughts. Racing thoughts also interfere with the ability to fall asleep. Manic states are always relative to the normal state of intensity of the afflicted individual; thus, already irritable patients may find themselves losing their tempers even more quickly and an academically gifted person may, during the hypomanic stage, adopt seemingly "genius" characteristics and an ability to perform and articulate at a level far beyond that which they would be capable of during euthymia. A very simple indicator of a manic state would be if a heretofore clinically depressed patient suddenly becomes inordinately energetic, cheerful, aggressive, or "over happy." Other, often less obvious, elements of mania include delusions (generally of either grandeur or persecution, according to whether the predominant mood is euphoric or irritable), hypersensitivity, hypervigilance, hypersexuality, hyper-religiosity, hyperactivity and impulsivity, a compulsion to over explain (typically accompanied by pressure of speech), grandiose schemes and ideas, and a decreased need for sleep (for example, feeling rested after only 3 or 4 hours of sleep). In the case of the latter, the eyes of such patients may both look and seem abnormally "wide open," rarely blinking, and may contribute to some clinicians’ erroneous belief that these patients are under the influence of a stimulant drug, when the patient, in fact, is either not on any mind-altering substances or is actually on a depressant drug, in a misguided attempt to ward off any undesirable manic symptoms. Individuals may also engage in out-of-character behavior during the episode, such as questionable business transactions, wasteful expenditures of money (e.g., spending sprees), risky sexual activity, abuse of recreational substances, excessive gambling, reckless behavior (such as "speed driving" or daredevil activity), abnormal social interaction (as manifest via, for example, over familiarity and conversing with strangers), or highly vocal arguments. These behaviours may increase stress in personal relationships, lead to problems at work and increase the risk of altercations with law enforcement. There is a high risk of impulsively taking part in activities potentially harmful to the self and others. Although "severely elevated mood" sounds somewhat desirable and enjoyable, the experience of mania is ultimately often quite unpleasant and sometimes disturbing, if not frightening, for the person involved and for those close to them, and it may lead to impulsive behaviour that may later be regretted. It can also often be complicated by the sufferer's lack of judgment and insight regarding periods of exacerbation of characteristic states. Manic patients are frequently grandiose, obsessive, impulsive, irritable, belligerent, and frequently deny anything is wrong with them. Because mania frequently encourages high energy and decreased perception of need or ability to sleep, within a few days of a manic cycle, sleep-deprived psychosis may appear, further complicating the ability to think clearly. Racing thoughts and misperceptions lead to frustration and decreased ability to communicate with others. Mania may also, as earlier mentioned, be divided into three “stages.” Stage I corresponds with hypomania and may feature typical hypomanic characteristics, such as gregariousness and euphoria. In stages II and III mania, however, the patient may be extraordinarily irritable, psychotic or even delirious. These latter two stages are referred to as acute and delirious (or Bell’s), respectively. Various triggers have been associated with switching from euthymic or depressed states into mania. One common trigger of mania is antidepressant therapy. Studies show that the risk of switching while on an antidepressant is between 6-69 percent. Dopaminergic drugs such as reuptake inhibitors and dopamine agonists may also increase risk of switch. Other medication possibly include glutaminergic agents and drugs that alter the HPA axis. Lifestyle triggers include irregular sleep wake schedules and sleep deprivation, as well as extremely emotional or stressful stimuli. Various genes that have been implicated in genetic studies of bipolar have been manipulated in preclinical animal models to produce syndromes reflecting different aspects of mania. CLOCK and DBP polymorphisms have been linked to bipolar in population studies, and behavioral changes induced by knockout are reversed by lithium treatment. Metabotropic glutamate receptor 6 has been genetically linked to bipolar, and found to be under-expressed in the cortex. Pituitary adenylate cyclase-activating peptide has been associated with bipolar in gene linkage studies, and knockout in mice produces mania like-behavior. Targets of various treatments such as GSK-3, and ERK1 have also demonstrated mania like behavior in preclinical models. Deep brain stimulation of the subthalamic nucleus in Parkinson's disease has been associated with mania, especially with electrodes placed in the ventromedial STN. A proposed mechanism involves increased excitatory input from the STN to dopaminergic nuclei. The mechanism underlying mania is unknown, but the neurocognitive profile of mania is highly consistent with dysfunction in the right prefrontal cortex, a common finding in neuroimaging studies. Various lines of evidence from post-mortem studies and the putative mechanisms of anti-manic agents point to abnormalities in GSK-3, dopamine, Protein kinase C and Inositol monophosphatase. Meta analysis of neuroimaging studies demonstrate increased thalamic activity, and bilaterally reduced inferior frontal gyrus activation. Activity in the amygdala and other subcortical structures such as the ventral striatum tend to be increased, although results are inconsistent and likely dependent upon task characteristics such as valence. Reduced functional connectivity between the ventral prefrontal cortex and amygdala along with variable findings supports a hypothesis of general dysregulation of subcortical structures by the prefrontal cortex. A bias towards positively valenced stimuli, and increased responsiveness in reward circuitry may predispose towards mania. Mania tends to be associated with right hemisphere lesions, while depression tends to be associated with left hemisphere lesions. Post-mortem examinations of bipolar disorder demonstrate increased expression of Protein Kinase C (PKC). While limited, some studies demonstrate manipulation of PKC in animals produces behavioral changes mirroring mania, and treatment with PKC inhibitor tamoxifen (also an anti-estrogen drug) demonstrates antimanic effects. Traditional antimanic drugs also demonstrate PKC inhibiting properties, among other effects such as GSK3 inhibition. Manic episodes may be triggered by dopamine receptor agonists, and this combined with tentative reports of increased VMAT2 activity, measured via PET scans of radioligand binding, suggests a role of dopamine in mania. Decreased cerebrospinal fluid levels of the serotonin metabolite 5-HIAA have been found in manic patients too, which may be explained by a failure of serotonergic regulation and dopaminergic hyperactivity. Limited evidence suggests that mania is associated with behavioral reward hypersensitivity, as well as with neural reward hypersensitivity. Electrophysiological evidence supporting this comes from studies associating left frontal EEG activity with mania. As left frontal EEG activity is generally thought to be a reflection of behavioral activation system activity, this is thought to support a role for reward hypersensitivity in mania. Tentative evidence also comes from one study that reported an association between manic traits and feedback negativity during receipt of monetary reward or loss. Neuroimaging evidence during acute mania is sparse, but one study reported elevated orbitofrontal cortex activity to monetary reward, and another study reported elevated striatal activity to reward omission. The latter finding was interpreted in the context of either elevated baseline activity (resulting in a null finding of reward hypersensitivity), or reduced ability to discriminate between reward and punishment, still supporting reward hyperactivity in mania. Punishment hyposensitivity, as reflected in a number of neuroimaging studies as reduced lateral orbitofrontal response to punishment, has been proposed as a mechanism of reward hypersensitivity in mania. In the ICD-10 there are several disorders with the manic syndrome: organic manic disorder (F06.30), mania without psychotic symptoms (F30.1), mania with psychotic symptoms (F30.2), other manic episodes (F30.8), unspecified manic episode (F30.9), manic type of schizoaffective disorder (F25.0), bipolar affective disorder, current episode manic without psychotic symptoms (F31.1), bipolar affective disorder, current episode manic with psychotic symptoms (F31.2). Before beginning treatment for mania, careful differential diagnosis must be performed to rule out secondary causes. The acute treatment of a manic episode of bipolar disorder involves the utilization of either a mood stabilizer (valproate, lithium, lamotrigine, or carbamazepine) or an atypical antipsychotic (olanzapine, quetiapine, risperidone, or aripiprazole). Although hypomanic episodes may respond to a mood stabilizer alone, full-blown episodes are treated with an atypical antipsychotic (often in conjunction with a mood stabilizer, as these tend to produce the most rapid improvement). When the manic behaviours have gone, long-term treatment then focuses on prophylactic treatment to try to stabilize the patient's mood, typically through a combination of pharmacotherapy and psychotherapy. The likelihood of having a relapse is very high for those who have experienced two or more episodes of mania or depression. While medication for bipolar disorder is important to manage symptoms of mania and depression, studies show relying on medications alone is not the most effective method of treatment. Medication is most effective when used in combination with other bipolar disorder treatments, including psychotherapy, self-help coping strategies, and healthy lifestyle choices. Lithium is the classic mood stabilizer to prevent further manic and depressive episodes. A systematic review found that long term lithium treatment substantially reduces the risk of bipolar manic relapse, by 42%. Anticonvulsants such as valproate, oxcarbazepine and carbamazepine are also used for prophylaxis. More recent drug solutions include lamotrigine and topiramate, both anticonvulsants as well. In some cases, long-acting benzodiazepines, particularly clonazepam, are used after other options are exhausted. In more urgent circumstances, such as in emergency rooms, lorazepam has been used to promptly alleviate symptoms of agitation, aggression, and psychosis. Sometimes atypical antipsychotics are used in combination with the previous mentioned medications as well, including olanzapine which helps treat hallucinations or delusions, asenapine, aripiprazole, risperidone, ziprasidone, and clozapine which is often used for people who do not respond to lithium or anticonvulsants. Verapamil, a calcium-channel blocker, is useful in the treatment of hypomania and in those cases where lithium and mood stabilizers are contraindicated or ineffective. Verapamil is effective for both short-term and long-term treatment. Antidepressant monotherapy is not recommended for the treatment of depression in patients with bipolar disorders I or II, and no benefit has been demonstrated by combining antidepressants with mood stabilizers in these patients. Some atypical antidepressants, however, such as mirtazepine and trazodone have been occasionally used after other options have failed. Society and cultureEdit In Electroboy: A Memoir of Mania by Andy Behrman, he describes his experience of mania as "the most perfect prescription glasses with which to see the world... life appears in front of you like an oversized movie screen". Behrman indicates early in his memoir that he sees himself not as a person suffering from an uncontrollable disabling illness, but as a director of the movie that is his vivid and emotionally alive life. There is some evidence that people in the creative industries suffer from bipolar disorder more often than those in other occupations.Winston Churchill had periods of manic symptoms that may have been both an asset and a liability. English actor Stephen Fry, who suffers from bipolar disorder, recounts manic behaviour during his adolescence: "When I was about 17 ... going around London on two stolen credit cards, it was a sort of fantastic reinvention of myself, an attempt to. I bought ridiculous suits with stiff collars and silk ties from the 1920s, and would go to the Savoy and Ritz and drink cocktails." While he has experienced suicidal thoughts, he says the manic side of his condition has had positive contributions on his life. 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Some examples of signs that can be linked to a disease by a clinician: High blood pressure: This can indicate a cardiovascular problem, an adverse reaction to medication, an allergy, or many... Clubbing of the fingers: This may be a sign of lung disease or a range of genetic diseases Each infectious disease has its own specific signs and symptoms. General signs and symptoms common to a number of infectious diseases include: Fever; Diarrhea; Fatigue; Muscle aches; Coughing; When to see a doctor. Seek medical attention if you: Have been bitten by an animal; Are having trouble breathing; Have been coughing for more than a wee The diseases are usually caused by many factors rather than a single cause. When we have a disease, we eventually show some signs, such as headaches, cough, cold, weakness. These signs are referred to as symptoms. In almost all diseases, symptoms are shown immediately after having been struck by the disease . A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showing on a medical scan. A symptom is something out of the ordinary that is experienced by an individual such as feeling feverish, a headache or other pain or pains in the body. A medical sign is an objective indication of a disease, injury, or abnormal phys In contrast, a bloody nose is a sign of injured blood vessels in the nose that can be detected by a doctor, a nurse, or another observer. Health-care professionals use symptoms and signs as clues that can help determine the most likely diagnosis when illness is present Heart disease; Hepatitis A; Hepatitis B; Hepatitis C; Hepatitis D; Hepatitis E; Histiocytosis (childhood cancer) HIV; Human papillomavirus; Huntington's disease; Hypermetropia; Hyperopia; Hyperthyroidism; Hypothyroid; Hypotonia; I. Impetigo; Infertility; Influenza; Interstitial cystitis; Iritis; Iron-deficiency anemia; Irritable bowel syndrome; Ignious Syndrom An example of this is hemophilia, a disorder that leads to excessive bleeding. Metabolic and endocrine, or hormone, disorders. These are abnormalities in the chemical signaling and interaction in.. Sign: Any objective evidence of disease, as opposed to a symptom, which is, by nature, subjective. For example, gross blood in the stool is a sign of disease; it is evidence that can be recognized by the patient, physician, nurse, or someone else. Abdominal pain is a symptom; it is something only the patient can perceive Some examples of physical illnesses are cancer, diabetes, Parkinson's disease and pneumonia. Other examples of physical illness are the common cold and sickle cell anemia. Cancer is a group of diseases that are characterized by an uncontrolled growth of abnormal cells. Common types of cancer begin in the lungs, breast, uterus, brain, stomach. Examples of diseases caused by animals are anthrax, plague and rabies. Transmission Through Certain Environmental Factors. Several infectious modes of disease transmission are available in water, plants and soil. They may come in contact with people who can cause diseases. Examples are hookworm and legionnaires' disease. Do It Yoursel What are Infectious Diseases? Infectious diseases are diseases caused by living organisms like viruses and bacteria. Described as contagious, they can be passed from person to person through body secretions, insects or other means. Examples are SARS, influenza, the common cold, tuberculosis (TB), Hepatitis A and B Common symptoms of gastrointestinal viral diseases include: abdominal cramps; diarrhea; vomiting; Examples. Examples of gastrointestinal viral diseases include: norovirus infection; rotavirus. For example, if the average duration of infection is three days, then, on average, one-third of the currently infected population recovers each day. (Strictly speaking, what we mean by infected is really infectious, that is, capable of spreading the disease to a susceptible person Examples include black lung disease from coal dust and asbestosis from asbestos dust. Lung Diseases Affecting the Interstitium The interstitium is the thin, delicate lining between your alveoli (b) Shows signs of progressive impairment; and (c) Activities of Daily Living assessment confirm the inability of the Life Assured to perform without assistance three (3) or more of the Activities of Daily Living. Only idiopathic Parkinson's Disease is covered. Drug-induced or toxic causes of Parkinsonism are excluded. 23. Chronic Liver Disease Alzheimer's disease progresses in several stages: preclinical, mild (sometimes called early-stage), moderate, and severe (sometimes called late-stage). Signs of Mild Alzheimer's Disease. In mild Alzheimer's disease, a person may seem to be healthy but has more and more trouble making sense of the world around him or her The Centers for Disease Control and Prevention (CDC) and the Alzheimer's Association have created the Healthy Brain Initiative's (HBI) State and Local Public Health Partnerships to Address Dementia: The 2018-2023 Road Map.. It is designed to focus the public health response to growing and future impacts of Alzheimer's and other dementias Disease management is an approach to health care that teaches patients how to manage a chronic disease. Patients learn to take responsibility for understanding how to take care of themselves. They learn to avoid potential problems and exacerbation, or worsening, of their health problem. Example: One step in teaching disease management to a. Plate 12 - A 5-day-old lesion on a steer's foot. Signs of early granulation are evident. Plate 13 - A 7-day-old lesion on a steer's foot. Healing is progressing underneath the necrotic epithelium. Plate 14- Another example of a 7-day-old inter-digital foot lesion on a steer. Plate 15 - An 11-day-old foot lesion on the heel bulb of a steer Examples of notifiable diseases include: diseases caused by bacteria such as legionellosis. diseases or conditions caused by viruses such as influenza, COVID-19 and HIV (Human Immunodeficiency Virus) infections spread by contact, such as hepatitis. infections spread through the gastrointestinal route, such as listeriosis Transfer of Disease Through Vector. Various insects and flies can transmit infections. These flies and insects sit and feed on multiple animals, humans, birds and bring along disease-causing agents. Further, when they go and sit on some uninfected person, the infection may get transferred. Lyme and malaria are two examples of vector-borne diseases A viral disease is any condition that's caused by a virus. There are several types of viral disease, depending on the underlying virus. We'll go over some of the main types, including how they. Although the signs and symptoms vary from disease to disease in this group, symptoms occur in each case because of an enzyme deficiency that inhibits the ability of the lysosomes present in each of the body's cells to perform their normal function. The lysosomes function as the primary digestive units within cells Disease Organism Main reservoirs Usual mode of transmission to humans; Anthrax: Bacillus anthracis: livestock, wild animals, environment: direct contact, ingestion, inhalatio For example, phenylketonuria (PKU) is a rare disease but has very serious long-term consequences if left untreated. PKU occurs in only 1 out of every approximately 15,000 births, and if left untreated can result in severe mental retardation that can be prevented with dietary intervention Kwashiorkor. Kwashiorkor is a disease caused by a severe deficiency of protein in diets that contain calories mostly from carbohydrates such as yams, rice and bananas. It usually affects older children. People with kwashiorkor appear puffy in the abdomen area from retention of fluid, according to the University of Maryland Medical Center In time, Paget's disease can lead to a number of other symptoms or complications that can be more serious: Bone expansion: Bone that's affected by Paget's disease expands and may become deformed. Long bones may curve so, for example, one leg may end up shorter than the other Visit us (http://www.khanacademy.org/science/healthcare-and-medicine) for health and medicine content or (http://www.khanacademy.org/test-prep/mcat) for MCAT.. headache, chills and fatigue]. Currently, the Centers for Disease Control and Prevention recommends that people with an infectious illness such as the flu remain at home until at least 24 hours after they are free of fever (100 degrees F or 37.8 degrees C) or signs of a fever without the use of fever-reducing medications Sickle cell disease is a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body.People with this disease have atypical hemoglobin molecules called hemoglobin S, which can distort red blood cells into a sickle, or crescent, shape.. Signs and symptoms of sickle cell disease usually begin in early childhood Diseased plants can be identified by abnormal growth or by signs of the disease-causing organism, such as bacterial slime (an external sign of a disease called bacterial wet wood) or insect larvae. What does sign mean? To relinquish or transfer title to by signature. (verb) Signed away all her claims to the estate For example, if an individual quits smoking, his or her risk of developing heart disease is greatly reduced. Many public health and health care interventions focus on changing individual behaviors such as substance abuse, diet, and physical activity. Positive changes in individual behavior can reduce the rates of chronic disease in this country with a disease or health condition.8,9 2. Secondary Prevention—screening to identify diseases in the earliest stages, before the onset of signs and symptoms, through measures such as mammography and regular blood pressure testing.10 3. Tertiary Prevention—managing disease post diagnosis to slow or sto Some diseases can be transferred by infected droplets contacting surfaces of the eye, nose, or mouth. This is referred to as droplet contact transmission. Droplets containing microorganisms can be generated when an infected person coughs, sneezes, or talks. Droplets can also be generated during certain medical procedures, such as bronchoscopy Examples Of Zoonotic Diseases . Zoonotic diseases have a long history. The Plague of Athens occurred in 430 BC and there are references to plagues in the Old Testament of the Bible. The number of potential zoonotic diseases today is impressive. You have likely heard of rabies, ringworm, and Lyme disease, but many other diseases pose a threat to. Employee Leave and Pay. EMPLOYER grants leave to employees who are absent because of an infectious disease that affects them or their family members. EMPLOYER allows employees to use their accrued annual or sick leave if they become ill or need to take leave to care for a family member. Employees also can use unpaid family and medical leave for. The list of inflammatory diseases, and autoimmune diseases, occur far more frequently in women than men. With the exception of ankylosing spondylitis which occurs at a ratio of 3:1 in men. The ratios of the other inflammatory disorders occurs at a frequency up to 9:1 in women In 2018, an upsurge in echovirus 30 (E30) infections was reported in Europe. We conducted a large-scale epidemiologic and evolutionary study of 1,329 E30 strains collected in 22 countries in Europe during 2016-2018. Most E30 cases affected persons 0-4 years of age (29%) and 25-34 years of age (27%) For example, some infectious diseases or cancerous wounds develop characteristic, offensive odours. Samples are easily obtained by wiping the subject's skin with an organic solvent such as acetone or by collecting VOCs emitted from the affected area directly onto an absorbent solid-phase microextraction (SPME) fibre Celiac disease can develop anytime from infancy to adulthood, most commonly between the ages of 10 and 40. In people with celiac disease, symptoms occur after consuming gluten. How it's treated Celiac disease can be effectively treated by removing all sources of gluten from the diet. This includes foods and drinks made with wheat, barley, and rye The location and nature of the disease often can be determined by the signs your pet shows. For example, abnormalities of biting, chewing, and swallowing usually are associated with diseases of the mouth, the teeth, the jaw, or the esophagus Crohn's Disease Definition Crohn's disease is a type of inflammatory bowel disease (IBD), resulting in swelling and dysfunction of the intestinal tract. Description Crohn's disease involves inflammation of the intestine, especially the small intestine. Inflammation refers to swelling, redness, and loss of normal function. There is evidence that the. Types of probability sampling with examples: Probability sampling is a sampling technique in which researchers choose samples from a larger population using a method based on the theory of probability. This sampling method considers every member of the population and forms samples based on a fixed process. For example, in a population of 1000. Diseases caused by just one copy of a defective gene, such as Huntington's disease, are rare. Thanks to natural selection, these dominant genetic diseases tend to get weeded out of populations over time, because afflicted carriers are more likely to die before reproducing Diseases Common Signs and Symptoms Prev Article Next Article Here are the comprehensive and most commonly used signs and symptoms of diseases to read ,review and contemplate for nurses reviewers and practitioners Pathognomonic sign is also known as hallmark sign. This is a kind of unique sign seen on patients having these diseases. These are used to easily distinguish one disease from another. However, these signs are not the basis for diagnosing clients. Laboratory tests are still needed before diagnosing clients A sign of plant disease is physical evidence of the pathogen. For example, fungal fruiting bodies are a sign of disease. When you look at powdery mildew on a lilac leaf, you're actually looking at the parasitic fungal disease organism itself (Microsphaera alni). Bacterial canker of stone fruits causes gummosis, a bacterial exudate emerging. ICD defines the universe of diseases, disorders, injuries and other related health conditions, listed in a comprehensive, hierarchical fashion that allows for: Easy storage, retrieval and analysis of health information for evidenced-based decision-making. Sharing and comparing health information between hospitals, regions, settings and countries For example, active carriers may transmit the disease during the incubation period (before they show signs and symptoms) or the period of convalescence (after symptoms have subsided). Active carriers who do not present signs or symptoms of disease despite infection are called asymptomatic carrier s This is a substance that is released when blood cells break down. Your baby may have a big liver, spleen, or heart. There may also be extra fluid in your baby's stomach, lungs, or scalp. These are signs of hydrops fetalis. This condition causes severe swelling (edema). Rh disease can cause problems in your newborn Parkinson's Disease. Parkinson's disease is a neurodegenerative disease. It causes a progressive deterioration of muscle function due to decreased dopamine in the brain. According to the Parkinson's Disease Foundation, motor symptoms include stiffness, tremor, postural changes, slowness, impaired balance, and shuffling gait Infectious Diseases - A to Z List. Chikungunya Virus Infection (Chikungunya) CDC. Clostridium Difficile Infection CDC. Coccidioidomycosis fungal infection (Valley fever) CDC. Creutzfeldt-Jacob Disease, transmissible spongiform encephalopathy (CJD) CDC. Encephalitis, Arboviral or parainfectious CDC A mixed episode of bipolar disorder features symptoms of both mania or hypomania and depression. Common signs of a mixed episode include depression combined with agitation, irritability, anxiety, insomnia, distractibility, and racing thoughts. This combination of high energy and low mood makes for a particularly high risk of suicide Knowing the early warning signs of lung disease can help you receive treatment before the disease becomes serious or even life threatening. If you experience any of the following warning signs, make an appointment with your healthcare provider as soon as possible. Early detection could save your life Crohn's is a chronic disease, which means patients will likely experience periods when symptoms are active, known as flares, followed by periods of remission when you may not notice any symptoms at all.. While it is important to recognize the signs of Crohn's disease, only a doctor can confirm a diagnosis . Here are some common examples: Severe combined immunodeficiency (SCID). This is an example of an immune deficiency that is present at birth. Children are in constant danger of infections from bacteria, viruses, and fungi. This disorder is sometimes called bubble boy disease. Osteoporosis is a degenerative disease affecting the bones. According to MedlinePlus, 1 out of 5 women over the age of 50 in the United States suffer from osteoporosis, a disease of decreased bone mass. Osteoporosis symptoms include bone pain, a stooped posture, bone fractures, a loss of height and low back pain due to fractures 1100 San Leandro Blvd. San Leandro, CA 94577 (510) 267-800 Abdominal pain is associated with anxiety and depression scores in a sample of the general adult population with no signs of organic gastrointestinal disease. S. A. Walter. Corresponding Author. Institution of Clinical and Experimental Medicine (IKE), Faculty of Health Sciences, Division of Gastroenterology, Linköping University, Linköping. Health, or lack of health, was once merely attributed to biological or natural conditions. Sociologists have demonstrated that the spread of diseases is heavily influenced by the socioeconomic status of individuals, ethnic traditions or beliefs, and other cultural factors. Where medical research might gather statistics on a disease, a sociological perspective of an illness would provide. . Mild cognitive impairment (MCI) is a condition that can be an early sign of Alzheimer's, but not everyone with MCI will develop the disease If you notice unusual signs of disease, abnormal behaviour or unexpected deaths in your stock, call the Animal Disease Emergency Hotline on 1800 675 888. This national service operates 24 hours a day, 7 days a week. Immediately report any of the notifiable incidents listed below: a lot of ill or dead animals including birds or aquatic animal Cancer is a disease in which some of the body's cells grow uncontrollably and spread to other parts of the body. Cancer can start almost anywhere in the human body, which is made up of trillions of cells. Normally, human cells grow and multiply (through a process called cell division) to form new cells as the body needs them 10. Cirrhosis: Cirrhosis can be defined as a group of liver disorders. Liver can be severely affected by heavy alcohol consumption and chronic hepatitis. This has become a common lifestyle disease. It is also easier to detect diseases that affect the wood of the vines after the leaves have dropped. Examples of possible confusion during scouting. Some diseases have similar signs and symptoms. A disease can have different signs and symptoms, sometimes depending on the grape variety. Several diseases can be present at the same time Therefore, In an attempt to better understand this dreaded disease, we provide you with a list of the most common symptoms. 1. Fatigue Fatigue. ALS is a syndrome with a varied evolution, and no two patients experience the same progression of symptoms. However, one of the earliest and most common signs of ALS is fatigue Example: Reyes Syndrome is a rare, but highly fatal disease in which the liver and brain become dysfunctional due to abnormal accumulation of cellular fat. It tends to occur when people are recovering from a viral illness, and it tends to be associated with use of aspirin, especially in children .Maybe that's because this debilitating inflammatory. Historically, persistent foamy urine noticed upon voiding is considered a warning sign of kidney disease. Foamy urine is characterized by the appearance and persistence of multiple layers of small to medium bubbles in urine voided into a container, such as a toilet bowl (see Figure 1).The appearance of a single layer of larger bubbles upon voiding, that quickly dissipate, can be considered normal A critical example is a developing model of infectious disease that shows that most epidemics — AIDS, Ebola, West Nile, SARS, Lyme disease and hundreds more that have occurred over the last. Given that stress has been linked as a co-factor in 95% or all disease processes, a keystone of holistic, alternative health and healing is learning how to effectively manage stress. This learning process begins with recognizing or identifying four specific types of stress affecting you and how these stressors (that is, what demands a change. Signs of pests and diseases that are unusual or exotic to Australia should be reported immediately. Pests found on imported goods, vessels and aircraft. IIf you see something that could have entered Australia with imported goods or in mail from overseas, report it by phoning the See. Secure Memory loss that disrupts daily life may be a symptom of Alzheimer's or other dementia. Alzheimer's is a brain disease that causes a slow decline in memory, thinking and reasoning skills. There are 10 warning signs and symptoms. If you notice any of them, don't ignore them. Schedule an appointment with your doctor . The earliest symptoms of autoimmunity, however, are very, very similar. So this was the good news. The bad news is, they're also vague, non-specific and sometimes, hard to identify as a reason for concern until the disease becomes acute Physical signs of worms. Almost all sheep have internal parasites. They often don't cause any disease and sheep can look normal or even fantastic. However if worms get out of control, sheep can suffer from both subclinical disease (no outward signs) or clinical disease (signs range from very subtle to obvious, including death) The portion of the sample made up of red blood cells. Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease I am uploading this to help dispel the notion that Alzheimer's disease just makes you forgetful. It is a Fatal disease that slowly kills your brain over the. Alzheimer Society of Canada. With the help of this downloadable brochure, you can identify the 10 signs of Alzheimer's disease, the most common type of dementia. Know the 10 warning signs of Alzheimer's disease. Alzheimer Society of Canada. This one-page, illustrated handout is an easy way to remember the 10 warning signs of Alzheimer's disease Mordecai's research has found that warmer temperatures increase transmission of vector-borne disease up to an optimum temperature or turn-over point, above which transmission slows. Just as they carry different diseases, different mosquitoes are adapted to a range of temperatures. For example, malaria is most likely to spread at 25. Hepatic encephalopathy is a neurologic syndrome caused by liver dysfunction and is seen in a number of liver diseases. Signs suggestive of hepatic encephalopathy include dullness, circling, head pressing, aimless wandering, weakness, poor coordination, blindness, excessive drooling, behavior changes (aggression for example), dementia, collapse, seizures, and coma	2	13	1	0	0	3	0.929494	4	4,888
Learning disorders: From the diagnostic manuals to the classrooms - The diagnostic criteria for learning disorders (LD) are included in the two most recognized classification systems of mental disorders: the International Classification of Diseases and Related Health Problems (ICD), developed by the World Health Organization (WHO), and the Diagnostic and Statistical Manual of Mental Disorders (DSM), from the American Psychiatric Association (APA). - The definition of LD describes persistent difficulties in learning academic skills that remain unaccounted for by intellectual, neurological or motor disorders, sensory impairment, lack of availability of education, or by psychosocial adversity. A significant impairment in academic or occupational performance is also required for the diagnosis. - Neuroscience research challenges the traditional classification systems and provides evidence in favour of a dimensional approach in researching the neurocognitive underpinnings of LD. Some neuroscience evidence is already integrated into the latest revisions of the definition of neurodevelopmental disorders (ICD-11 and DSM-5). - The implementation of internationally shared criteria for the identification of individuals with LD and the dissemination of these criteria is strongly recommended, based on its implications for further research in diagnosis and remediation/intervention strategies, and for implementation of individual access to resources and support. What does it mean that a child presents with one or more LD? Which criteria are used to establish such a diagnosis? Are children, parents, teachers, school administrators, and policy makers sufficiently informed about the implications of such a diagnosis? Here, you will be presented with the two most recognized classification systems of mental disorders, which include definitions and diagnostic criteria for neurodevelopmental disorders in general, and for LD in particular. The rationale and key concepts behind the design of the diagnostic classifications, their application to clinical practice and research, and the implications in terms of access to health services and educational resources will also be discussed. Classification systems of mental disorders A classification is “an exhaustive set of mutually exclusive categories to aggregate data at a pre-prescribed level of specialization for a specific purpose (ISO 17115)”1. In other words, classification involves the categorization of events, objects, or behaviours in accordance to specific rules or criteria that allow identification of a common set of traits or fundamental “nature” across the collection under analysis but also reflects a specific intentionality, since they are established for attaining specific purposes. From a philosophical point of view, in science, there are different views regarding how to classify phenomena. One view is that a scientific classification system should reflect the inherent “true essence” or “natural” structure of the world (“essentialism”). Hence, membership to a specific class is decided in accordance to definitive, binary criteria, so that it is always clear whether something belongs or not to a specific category because it is the inherent structure of the world in itself, and not our interests, that guides classification. On the other hand, arbitrary or artificial classifications are also possible when the phenomenon at hand can be measured and better described as a continuum or “dimension.” In this case, it is possible to assign different values along the dimension used to quantify events or, say, behaviours, such as those relating to emotional expression or physical activity. In this instance, some people might be assigned higher and some lower values on the dimension. Of course, it is possible to produce a categorical classification out of dimensions, by using arbitrary cutoffs and creating subgroups. It is also possible to combine clear-cut categorical classifications and dimensional classifications that have been proven relevant when studying specific phenomena (“empiricism”). Finally, the goals behind uncovering consistent patterns and producing classifications are also highly influential when designing and adopting a classification system (“pragmatism”)2. All these factors are critical. Take, for example, the case of psychiatric classification of mental health disorders. This stems from the observation of patterns of signs, symptoms, and traits that co-vary with the presence of specific forms of mental illness. This, in turn, may be traced back to the existence of biophysical and psychological factors that act as determinants of human development and interact with a limited and repetitive range of experiences to which people are exposed throughout their lives2, across cultures. Clinical classification assumes that shared covariance of signs and symptoms can be used to distinguish among classes of patients (although even patients within the same diagnostic category can display differences in signs and symptoms between them). The goals for a classification system for mental disorders include selecting treatment, increasing the homogeneity in the study of the factors that cause the disorders by producing more similar groups of subjects to be studied, maximizing the detection of individuals exhibiting disorders (“true positives”) and healthy ones (“true negatives”), being measurable, being consistent with genetics and physiology data, being culturally congruent and clinically informative2. Health practitioners, particularly psychiatrists, employ the diagnostic manuals derived from the classification systems to determine the presence of mental disorders in the population. However, the currently available manuals describe symptoms and signs but are not able to explain the disorders. Hence, additional efforts are required to ascertain the validity, clinical utility, and cross-cultural applicability of the adopted diagnostic criteria, and to avoid the reification of the classifications. The most recognized classification systems for mental disorders are currently the International Classification of Diseases and Related Health Problems, now in its eleventh revision (ICD-11)1, and the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)3. The ICD, developed by the World Health Organization (WHO), provides a common language for defining and communicating data about diseases and health conditions, including, mental, behavioural, or neurodevelopmental disorders. WHO’s member states have agreed to use ICD as a framework for reporting health information to make data internationally comparable. ICD-6, approved in 1948, was the first version to include a classification of mental disorders4. ICD-10, the version currently in use, is the international standard for reporting diseases and health conditions. It is proposed to be used as the diagnostic classification standard for clinical and research purposes and allows the monitoring of the incidence and prevalence of diseases and the description of trends in health reimbursements and resource allocation. The ICD-11 was approved by the 62nd World Health Assembly in May 2019, to come into effect on January 1st, 2022. On the other hand, the DSM, developed by the American Psychiatric Association (APA) was heavily influenced by previous American classification systems and the ICD-6. DSM-5, adopted in 2013, is the most recent version of the manual and was designed as an evidenced-based tool to guide clinicians in the assessment and diagnosis of psychiatric disorders5. Due to its compatibility with the corresponding ICD codes, DSM-5 is also used for billing purposes and for providing access to educational support in the United States of America and elsewhere. Both diagnostic systems have undergone extensive international expert consultations and field trials, conducted in clinical practice settings, to test their clinical utility5-6. The results of a global survey including 4,887 psychiatrists in 44 countries regarding their use of diagnostic classification systems in clinical practice, and the desirable characteristics of a classification of mental disorders, in the context of the revision of the ICD-10, showed that ICD-10 is the classification system psychiatrists use most in their daily clinical work (70.1% of the global sample), while the next was the DSM-IV (23.0%). A reported 5.6% of the sample used other classification systems (the Chinese Classification of Mental Disorders, the Cuban Glossary of Psychiatry, or the French Classification of Child and Adolescent Mental Disorders) and the rest (1.3%) reported they used previous versions of the ICD (ICD-9 or ICD-8). Use of ICD-10 was predominant in Europe. The DSM-IV was nearly universally used in the United States but was also common in other countries such as Argentina, Australia, Kenya, and Turkey7. Whereas the ICD is mostly used in everyday clinical practice, most (psychopathology) researchers seem to use the DSM operational criteria.5 Neurodevelopmental disorders and learning disorders What does it mean that a child presents with one or more LD? According to the DSM-5, the diagnostic criteria for specific LD include3: - Difficulties learning and using academic skills, as indicated by the presence of at least one of the following symptoms that have persisted for at least six months, despite the provision of interventions that target those difficulties: - Inaccurate or slow and effortful word reading (e.g., reads single words aloud incorrectly or slowly and hesitantly, frequently guesses words, has difficulty sounding out words) - Difficulty understanding the meaning of what is read (e.g., may read text accurately but not understand the sequence, relationships, inferences, or deeper meanings of what is read) - Difficulties with spelling (e.g., may add, omit, or substitute vowels or consonants) - Difficulties with written expression (e.g., makes multiple grammatical or punctuation errors within sentences; employs poor paragraph organization; written expression of ideas lacks clarity) - Difficulties mastering number sense, number facts, or calculation (e.g., has poor understanding of numbers, their magnitude, and relationships; counts on fingers to add single-digit numbers instead of recalling the math fact as peers do; gets lost in the midst of arithmetic computation and may switch procedures) - Difficulties with mathematical reasoning (e.g., has severe difficulty applying mathematical concepts, facts, or procedures to solve quantitative problems) - The affected academic skills are substantially and quantifiably below those expected for the individual’s chronological age, and cause significant interference with academic or occupational performance, or with activities of daily living, as confirmed by individually administered standardized achievement measures and comprehensive clinical assessment. For individuals age 17 years and older, a documented history of impairing learning difficulties may be substituted for the standardized assessment. - The learning difficulties begin during school-age years but may not become fully manifest until the demands for those affected academic skills exceed the individual’s limited capacities (e.g., as in timed tests, reading or writing lengthy complex reports for a tight deadline, excessively heavy academic loads). - The learning difficulties are not better accounted for by intellectual disabilities, uncorrected visual or auditory acuity, other mental or neurological disorders, psychosocial adversity, lack of proficiency in the language of academic instruction, or inadequate educational instruction. Additionally, the classification allows for the specification of current severity, in terms of: - Mild—some difficulties learning skills in one or two academic domains, but the individual may be able to compensate or function well when provided with appropriate accommodations or support services. - Moderate—marked difficulties learning skills in one or more academic domains, the individual is unlikely to become proficient without some intervals of intensive and specialized teaching during the school years. Some accommodations or supportive services at least part of the day at school, in the workplace, or at home may be needed to complete activities accurately and efficiently. - Severe—severe difficulties affecting several academic domains, the individual is unlikely to learn those skills without ongoing intensive individualized and specialized teaching for most of the school years. Even with an array of appropriate accommodations or services at home, at school, or in the workplace, the individual may not be able to complete all activities efficiently. All diagnostic criteria are to be met based on a clinical synthesis of the individual’s history (developmental, medical, family, educational), school reports, and psychoeducational assessment. In the case of ICD-11, which follows a developmental approach, the equivalent term is developmental LD, and it is characterized by significant and persistent difficulties in learning academic skills, which may include reading, writing, or arithmetic. The individual’s performance in the affected academic skill(s) is markedly below what would be expected for chronological age and general level of intellectual functioning, and results in significant impairment in the individual’s academic or occupational functioning. Developmental LD first manifest when academic skills are taught during the early school years. Developmental LD are not due to a disorder of intellectual development, sensory impairment (vision or hearing), neurological or motor disorder, lack of availability of education, lack of proficiency in the language of academic instruction, or psychosocial adversity (Chapter 6)1. Both diagnostic systems include specifiers for the different academic domains and subskills addressed in the definitions (see Table 1). For ICD-11, severity levels are not specified. Table 1. Domains specified in the definitions of DSM-5 and ICD-11 of LD. \|DSM-5: Neurodevelopmental disorders (31): \|ICD-11: Neurodevelopmental disorders: 6A03 Developmental LD: \|315.00 (F81.0) With impairment in reading: Note: Dyslexia is an alternative term used to refer to a pattern of learning difficulties characterized by problems with accurate or fluent word recognition, poor decoding, and poor spelling abilities. If dyslexia is used to specify this particular pattern of difficulties, it is important also to specify any additional difficulties that are present, such as difficulties with reading comprehension or math reasoning. \|6A03.0 Developmental LD with impairment in reading: Characterized by significant and persistent difficulties in learning academic skills related to reading, such as word reading accuracy, reading fluency, and reading comprehension. Inclusions: Developmental dyslexia Exclusions: Disorders of intellectual development \|315.2 (F81.81) With impairment in written expression: \|\|6A03.1 Developmental LD with impairment in written expression: Characterized by significant and persistent difficulties in learning academic skills related to writing, such as spelling accuracy, grammar and punctuation accuracy, and organization and coherence of ideas in writing. Exclusions: Disorders of intellectual development \|315.1 (FBI .2) With impairment in mathematics: Note: Dyscalculia is an alternative term used to refer to a pattern of difficulties characterized by problems processing numerical information, learning arithmetic facts, and performing accurate or fluent calculations. If dyscalculia is used to specify this particular pattern of mathematic difficulties, it is important also to specify any additional difficulties that are present, such as difficulties with math reasoning or word reasoning accuracy. \|6A03.2 Developmental LD with impairment in mathematics: Characterized by significant and persistent difficulties in learning academic skills related to mathematics or arithmetic, such as number sense, memorization of number facts, accurate calculation, fluent calculation, and accurate mathematic reasoning. Exclusions: Disorders of intellectual development \|6A03.3 Developmental LD with other specified impairment of learning: Characterized by significant and persistent difficulties in learning academic skills other than reading, mathematics, and written expression. Exclusions: Disorders of intellectual development 6A03.Z Developmental LD, unspecified However, which tests should be employed or how to determine if performance is significantly lower than expected is not specified in the manuals and is the decision of the specialists involved with the diagnosis (see ref. 8 for an analysis of the different approaches to LD identification). Neuroscience and the definition of specific learning disorders Although the diagnosis of LD may seem relatively straightforward, indisputable evidence of their neurocognitive underpinnings remains elusive. Neuroscientists have committed to elucidating the neurocognitive architecture underlying LD with one major focus seeking to determine whether LD arise from the damage of basic abilities (such as phonological awareness for reading or number sense for math) required to acquire and process information in specific domains (the so-called “single deficit view”), or whether LD is the combined result of several dysfunctional mechanisms9-14. The latter hypothesis has driven most of the research conducted on the subject, although the former has been supported by evidence showing different cognitive processes are affected in children with LD15. In this context, some neuroscientists have challenged the notion of LD being specific or even whether they should be termed as disorders; and there are advocates for a dimensional description of learning and academic performance that incorporates children that might otherwise be diagnosed with LD9. They argue the classification relies on arbitrary and often variable cutoffs that do not reflect the existence of qualitatively different neurocognitive foundations of performance in children with LD. Also, they allude to the high heterogeneity in the neurocognitive and academic performance profiles within the groups identified and the consistent co-occurrence of difficulties across multiple learning domains, or comorbity, among disorders. However, neuroscientists do not deny the practical value and clinical necessity of the fundamentally categorical classification systems currently in place and suggest their criticisms apply primarily to the research agenda in the field15. Note the ICD-11 definition does not includes the term “specific,” but does include the term “developmental.” Also, the design of both major classification systems is fundamentally evidence-based and considers data produced from cognitive neuroscience and neuropsychology. Also, the diagnostic manuals, although they are not “dimensional” systems per se, acknowledge the continuous nature of performance and the variability at the core of LD. In fact, both systems have included deficits in all domains of learning in the same diagnostic category. Implications for teachers and policy makers The implementation of up-to-date, standardized diagnostic criteria for LD is strongly recommended and, more specifically, the ICD-11 criteria, given current agreements among the WHO member states. The dissemination of these criteria among parents, teachers, school administrators, and policy makers is advisable, since their timely implementation has practical implications in terms of early detection, appropriate diagnosis, and access to remediation/intervention strategies, resources, and support. Within clinical settings, the diagnosis of LD implies more access to remedial teaching, special programs, and accommodations9. In most countries, provision of medical services also depends upon a qualifying diagnosis and so, in the absence of LD diagnosis, children and families may encounter difficulty in getting access available resources and intervention programs. The process of integrating ICD within clinical processes is already on the way. This has been facilitated by the development of electronic health records and infrastructure for health care, automated treatment algorithms and care pathways, and increased implementation of standards of care and evidence-based guidelines, most of which rely on diagnostic categories4. Hence, it is advisable to work towards matching and keeping track of diagnoses and services, both in clinical and educational settings. The resulting information will allow assessment of the delivery of specific resources or programs and their corresponding outcomes. However, the legal implications and instruments required to achieve these kinds of applications of ICD in health/education systems need to be revised in the light of national and local laws and regulations. Finally, active participation of teachers, school psychologists, and administrators, and the inclusion of educational settings involved in the attention to neurodevelopmental disorders in the field studies of future revisions of the ICD are also recommended. - World Health Organization. (2018). International classification of diseases for mortality and morbidity statistics (11th Revision). Retrieved from https://icd.who.int/browse11/l-m/en - Millon, T., Krueger, R. F., & Simonsen, E. (2010). Contemporary directions in psychopathology: Scientific foundations of the DSM-5 and ICD-11. New York: Guilford Press. - American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596 - Clark, L. A., Cuthbert, B., Lewis-Fernández, R., Narrow, W. E., & Reed, G. M. (2017). Three approaches to understanding and classifying mental disorder: ICD-11, DSM-5, and the National Institute of Mental Health’s Research Domain Criteria (RDoC). Psychological Science in the Public Interest, 18(2), 72–145. doi:10.1177/1529100617727266 - Tannock, R. (2012). Rethinking ADHD and learning disorders in DSM-5: proposed changes in diagnostic criteria. Journal of Learning Disabilities, 46(1), 5–25. doi:10.1177/0022219412464341 - Keeley, J.W. et al. (2016). Developing a science of clinical utility in diagnostic classification systems field study strategies for ICD-11 mental and behavioral disorders. American Psychologist, 71(1), 3–16. doi: 10.1037/a0039972 - Reed, G. M., Correia, J. M., Esparza, P., Saxena, S., & Maj, M. (2011). The WPA-WHO Global Survey of Psychiatrists’ Attitudes Towards Mental Disorders Classification. World Psychiatry, 10(2), 118–131. doi:10.1002/j.2051-5545.2011.tb00034.x - Hale, J. et al. (2010). Critical issues in response-to-intervention, comprehensive evaluation, and specific learning disabilities identification and intervention: an expert white paper consensus. Learning Disability Quarterly, 33(3), 223–236. doi:10.1177/073194871003300310 - Gori, S., Seitz, A. R., Ronconi, L., Franceschini, S., & Facoetti, A. (2015). Multiple causal links between magnocellular–dorsal pathway deficit and developmental dyslexia. Cerebral Cortex, 26(11), 4356–4369. doi:10.1093/cercor/bhv206 - Slot, E. M., van Viersen, S., de Bree, E. H., & Kroesbergen, E. H. (2016). Shared and unique risk factors underlying mathematical disability and reading and spelling disability. Frontiers in Psychology, 7. doi:10.3389/fpsyg.2016.00803 - Karipidis, I. I. et al. (2018). Simulating reading acquisition: The link between reading outcome and multimodal brain signatures of letter–speech sound learning in prereaders. Scientific Reports, 8(1). doi:10.1038/s41598-018-24909-8 - Estévez-Pérez, N., Castro-Cañizares, D., Martínez-Montes, E. and Reigosa-Crespo, V. (2019). Numerical processing profiles in children with varying degrees of arithmetical achievement. Acta Psychologica 198 (2019) 102849. https://doi.org/10.1016/j.actpsy.2019.05.001 - Rykhlevskaia, E., Uddin, L. Q., Kondos, L., & Menon, V. (2009). Neuroanatomical correlates of developmental dyscalculia: combined evidence from morphometry and tractography. Frontiers in Human Neuroscience, 3:51,doi: 10.3389/neuro.09.051.2009 - Döhla, D., & Heim, S. (2016). Developmental dyslexia and dysgraphia: what can we learn from the one about the other? Frontiers in Psychology, 6. doi:10.3389/fpsyg.2015.02045 - Peters, L., & Ansari, D. (2019). Are specific LD truly specific, and are they disorders? Trends in Neuroscience and Education, 100115. doi:10.1016/j.tine.2019.100115	2	4	4	0	0	3	0.670956	7	4,954
Imaging of cerebrovascular development in larval zebrafish is described. Techniques to facilitate 3D imaging and modify cerebrovascular development using chemical treatments are also provided. Zebrafish are a powerful tool to study developmental biology and pathology in vivo. The small size and relative transparency of zebrafish embryos make them particularly useful for the visual examination of processes such as heart and vascular development. In several recent studies transgenic zebrafish that express EGFP in vascular endothelial cells were used to image and analyze complex vascular networks in the brain and retina, using confocal microscopy. Descriptions are provided to prepare, treat and image zebrafish embryos that express enhanced green fluorescent protein (EGFP), and then generate comprehensive 3D renderings of the cerebrovascular system. Protocols include the treatment of embryos, confocal imaging, and fixation protocols that preserve EGFP fluorescence. Further, useful tips on obtaining high-quality images of cerebrovascular structures, such as removal the eye without damaging nearby neural tissue are provided. Potential pitfalls with confocal imaging are discussed, along with the steps necessary to generate 3D reconstructions from confocal image stacks using freely available open source software. Zebrafish provide a powerful system to study developmental biology, and the relative transparency of their embryos is amenable to imaging-based studies1. The zebrafish has now been used as a model for vertebrate development for decades. Teleosts, including zebrafish, have a simplified vertebrate vascular system that has no reasonable homolog in invertebrates. Blood is pumped from the anterior chamber of a two-chambered heart through gills, where it is oxygenated. Blood from the gills converges at the dorsal aorta and passes through arteries that branch into smaller and smaller vessels, eventually reaching capillaries in organ tissues. Within capillaries oxygen is released and carbon dioxide is absorbed. On the venous side of capillaries blood flows into larger and larger veins and is finally drawn into the posterior chamber of the heart, where the cycle repeats. An adult zebrafish can lay 200 or more eggs at a time, and once fertilized, they develop quickly2. Within one day the body axis is well developed, including muscles that contract and move the embryo around inside the chorionic membrane. From 2-7 days post-fertilization (dpf) most body systems develop, including eyes and a central nervous system that can coordinate swimming toward food or away from bright light. Up to 7 dpf embryos are small enough to allow for visualization with microscopy. Transgenic lines that express fluorescent proteins can be imaged with confocal or fluorescence microscopy. Confocal imaging can be paired with open-source software3 to create 3D renderings of complete vascular structures in zebrafish embryos that provide a systems biology perspective of vascular development. Studies concerned with changes in vascular and cerebrovascular complexity will benefit from this protocol as it allows for a systems level analysis of vascular networks4,5. A compilation of methods and resources are provided to allow for easy adoption and of these techniques for studies that require imaging of vascular structures in embryonic zebrafish. The cost efficiency of zebrafish as an animal model is combining with emerging imaging technologies to provide new platforms with which to assess angiogenic effects of molecular pathways in vertebrate development and homeostasis. 1. Zebrafish Husbandry, Embryo Generation, and Treatment - Conduct the following zebrafish protocols under the guidance of an institutional animal care and use committee (IACUC) and within animal care guidelines of the NIH or other regulatory bodies/guidelines. - Zebrafish strains that express fluorescent proteins in specific tissues, cells, or organs are available from the Zebrafish International Resource Center (ZIRC). For example, Tg (kdr:EGPF)s843 express EGFP in vascular endothelial cells6, which can be used to produce complete 3D vascular structures as shown in this protocol. Other lines of transgenic zebrafish are available from ZIRC. - House adult zebrafish in an appropriate aquaculture system that monitors pH, salinity, temperature, dissolved oxygen, light, and other environmental factors7. The zebrafish shown here were housed in an Aquaneering Inc. system (San Diego, CA) at 28.5 °C with a 14 hour light/10 hour dark cycle. Feed adult zebrafish a balanced diet of brine shrimp and NRD 4/6 Fish food (Brine Shrimp Direct, Ogden, Utah). - Adult male and female zebrafish of breeding age should be housed separately to increase mating successful. - Stimulate egg laying and fertilization by placing females (2-4) and males (4-6) together in a mating container that has a mesh bottom with holes large enough for the eggs to fall through, but too small for the zebrafish adults to pass. Set up matings the evening before; eggs are laid near dawn, usually while the daytime light cycle slowly increases in intensity (dawn). Check for eggs at the bottom of the mating container every 15-30 minutes. - Collect eggs using a mesh strainer and clean with E3 buffer (5 mM NaCl, 0.17 mM KCl, 0.33 mM CaCl2, 0.33 mM MgSO4). Transfer the eggs to 100 mm culture plates filled with E3 buffer and store in a 28 °C incubator. - To study chemicals that alter cerebrovascular branching add desired chemical concentrations. For example neovasular branching can be induced with γ-secretase inhibitor (GSI IX/DAPT/N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycinet-butyl ester) solubilized in DMSO4, beginning 24 hours post fertilization (hpf). At that time-point embryos are still within the chorion, and many chemicals can pass through it8. If a treatment condition has neural or motor effects that may impair the ability of embryos to break free of the chorion, then embryos should be de-chorionated between 24 and 48 hpf, which can be done with either forceps of pronase2. Embryos shown in the images provided were dechorionated by gently grabbing the chorion with two sharpened forceps and tearing it open. - If needed/desired, pigment formation can be inhibited by adding 0.003% N-Phenylthiourea (PTU) to the E3 buffer at 24 hpf. 2. Confocal Imaging of Cerebrovascular Structures in Fixed Zebrafish Embryos - Sacrifice embryos in 250 mg/L Tricaine methanesulfonate, and then fix them by immersion in 2 - 4% paraformaldehyde overnight at 4 °C. Containers with fluorescent embryos should be wrapped in foil. Once fixed, embryos should be stored in PBS at 4 °C until imaged - EGFP fluorescence intensity becomes less resolved after about a week, but morphology (as viewed in bright field) is preserved much longer. - Prepare to mount the embryo by first removing one eye using a sharpened tungsten needle. Cut around the tissue connecting the eye first then cut the muscles, and finally cut the optic nerve to displace the eye. (Note: If imaging both sides is desired remove both eyes.) - Once the eye is removed, mount the embryo on a coverglass using a drop of 3% methylcellulose. Orient the embryo so that the side with the removed eye is facing the coverglass and is as close to the glass as possible. Cover the entire embryo with methylcellulose to prevent desiccation during imaging. - Image the mounted embryo immediately using an inverted confocal microscope equipped with a high-quality 20x Plan Apo objective (numerical aperture = 0.75 or better). This configuration is preferable to a non-inverted microscope that would require sandwiching the embryo between two glass planes, and pressing the embryo against the top glass. - Collect optical slices in 1 µm increments using a medium or large aperture setting. Larger steps of 2.5 µm can also be used, but it may be more difficult to determine the spatial order of smaller objects. Small apertures produce sharper detail, but the longer scans required may bleach EGFP and also limit the depth of imaging into the embryo that can be achieved. A confocal microscope allows for imaging about half-way through an embryo. - If imaging of the entire fish is desired, remove both eyes at the outset (see Note in step 3.2), rotate the embryo after imaging one side and repeat steps 2.3 - 2.5 for the opposite side. 3. 3D Reconstruction of Embryonic Zebrafish Cerebrovasculature - Use the Fiji distribution3 of open source ImageJ (http://fiji.sc), which is optimized for 3D renderings, free of charge, and compatible with PC, Mac and Linux computers. - Import confocal stacks to Fiji by going to Plugins>LOCI>BioFormats Importer 9 then select the confocal file, e.g. name.ids for Nikon stacks (Figure 2A). Select View stack with Hyperstack, Color mode: grayscale, check autoscale, check split channels. - These selections will open four separate channel panels; for EGFP only one will be needed, usually the third one down. Close the other three panels (red, blue and alpha) leaving the 16-bit image with a long name followed by C=1 (Figure 2A). - Adjust threshold by scanning though the image using the scroll tab along the bottom to find a slice that has the region or structure of interest, then go to Image>Adjust>Threshold (Figure 2C). - In the panel that comes up, slide the top bar (black level) to the left so that the structure can be seen quite well over background, and leave the bottom slide (white level) where it is (Figure 2D). Select B&W, select Dark background. Do not select calculate Threshold for each image unless different adjustments are required for each slice, select Black background. This process creates a new 8-bit image. - WARNING: Threshold cannot be undone or saved in ImageJ, so the confocal stack will have to be reloaded every time a change is needed. Write down the numbers and try different settings until the desired result is achieved. - Go to Plugins>3D Viewer>Threshold 0, Resampling factor 1 (best) or 2 (good), deselect the red and blue color boxes to make a green 3D output - otherwise it will produce a white rendering - select Apply (not Auto) (Figure 2E). - Rotate, spin and zoom the 3D image using the mouse and keyboard controls (Figure 2F). - Save still images at any point by using the capture option in the menu. The size of the image box on the screen dictates pixel dimensions of the image produced so if a high resolution image is desired make the box larger by dragging the bottom right corner. - Create a spinning 3D movie by selecting View>Record 360 deg rotation (Figure 2G). Rotation defaults to 2 degrees per step, but it can be changed to 5 degrees for example, which will create much smaller file sizes, but may add jerkiness to the animation. - Save the file in one of several available formats for later viewing with media players, uploading to the Internet, or using in PowerPoint presentations. The open source media player, VLC (http://www.videolan.org/vlc/index.html), is free of charge and handles these videos very well. 3D reconstruction of vascular structures provides a comprehensive and visually interesting perspective of zebrafish development. Figures 1 and 2 show methods as they typically done. Figure 3 shows several angles of vascular structures in a 6 dpf zebrafish embryo that expressed EGFP in endothelial cells. With a solid green or white color it can be difficult to appreciate signal intensity; pseudo-coloring provide image intensity from a look-up-table and allows better depth perception when structures overlap. An example of a pseudo-colored 3D image of the vasculature in a 6 dpf zebrafish is provided in Figure 4. Fluorescence imaging of live embryos can be used to study physiological characteristics that include eye and body movement, and cardiac activity. Figures 3 and 4 show representative results obtained with these methods, using the transgenic zebrafish line described. Imaging resolution depends on microscope characteristics, but the brightness of the EGFP signal is sufficient for good image quality with most commercial systems. Reconstruction and rendering of 3D representations is consistent and options within this open-source software provide consistently good results. Figure 1. Eye removal. A) A fixed 3 dpf embryo with a tungsten need positioned next to the eye. Tissue is cut around the eye from this position. B) The eye is falls out and the underlying ocular muscles and optic nerve are cut. The empty eye socket is indicated with dashed circle. C) The same embryo is turned over and mounted with methyl-cellulose, with the intact eye facing up. Please click here to view a larger version of this figure. Figure 2. Step-by-step 3D reconstruction of a confocal image stack. A) Open file (4104.1.ids) loaded within Fiji using Plugins>LOCI>Bioformat to select. B) After finding a slice with the region of interest, threshold adjustment is selected as shown. C) Threshold is adjusted to 214 using the top slider and apply is selected. D) 3D viewer is called as shown. E) The 3D reconstruction is shown of a zebrafish with the eye intact, for orientation. F) The image has been zoomed and rotated. G) A 360 degree rotation movie is made as shown. Please click here to view a larger version of this figure. Figure 3. Perspectives from 3D reconstruction. A) Medial perspective of 6 dpf embryo imaged with 10x objective, mouth is on the right, not gills inside mouth. B) Lateral of the same embryo, note fin is a loop in the middle. C) Same embryo imaged with 20x objective, medial perspective, note gill resolution. D) Lateral perspective of 20x objective imaging. The fin is on the right edge of the panel. E) Antero-medial view of 20x objective imaging, note gills inside mouth. F) Abdomen of the same embryo imaged with a 20x objective, head it to the right. Note vasculature on the yolk sac at the bottom right. Please click here to view a larger version of this figure. Figure 4. Intensity differences in 6 dpf embryo. Image of a 6 dpf reconstruction using a pseudocolor look-up-table for signal intensity. Mouth, brain, gills and yolk sac are labeled for orientation. Please click here to view a larger version of this figure. Figure 5. Movie of reconstructed vascular system in a 4 dpf zebrafish. The fish was imaged at 2.5 μm. The images were from imaging one half of the embryo. Compare vascular structures with structures in a GSI-treated zebrafish provided in Figure 6. Note the lower density of blood vessels in the head and larger gills. (See the "Zfish_spin.avi" supplemental file under Downloads) Figure 6. 3D Movie of vascular system in a GSI-treated embryo at 4 dpf. The fish was imaged at 2.5 μm through from lateral to midline. Compare vascular structures with the control 4 dpf fish shown in Figure 5. The arched back and smaller size are typical in embryos treated with this chemical. (See the "GSI-treated_4dpf_fish.avi" supplemental file under Downloads) The methods described here provide a foundation for visual studies of the vascular system in developing zebrafish. Live specimens can be used to assess physiological parameters, such as heart rate and heart stroke volume, while fixed samples can be used for high-resolution confocal imaging. Drosophila and C. elegans allow for whole body imaging, but zebrafish are vertebrates and provide a useful model for vertebrate tissues, including an endothelial cell-lined vascular system. These studies can incorporate significant transgenic lines and genomic resources from the zebrafish research community. 3D reconstruction and rendering of confocal images from embryonic zebrafish, as described here, allow for a systems biology approach to vascular branching and blood vessel density that is not possible with larger animal models such as rats and mice. Further, as amniotes zebrafish develop in a modifiable environment (E3 buffer), where one can easily add chemicals that inhibit specific enzymes or other processes that affect vascular development. The concentration and timing of chemical delivery can be altered, enabling the researcher to fine-tune treatment conditions. 1. Modifications and troubleshooting Modifications to this system can incorporate transgenic lines of zebrafish that express EGFP or other fluorescent proteins in a variety of tissue, organ or region specific patterns10. Further, analysis of neovascular changes in the zebrafish retina has recently been published5. Problems with pigmentation in older embryos and adult zebrafish can be compensated by crossing with transgenic lines that do not produce scale pigments or retinal pigment. Problems with diminished fluorescence typically result from inappropriate fixation conditions. Paraformaldehyde (4%) for 1 day is optimal, but stronger fixatives, such as glutaraldehyde, osmium tetroxide or alcohol, may destroy EGFP fluorescence. After fixation, embryos should be kept in PBS at 4 °C and always protected from direct sunlight. 2. Limitations of this technique The quality and resolution of 3D renderings produced with this protocol depend on the quality of images generated. Light penetration through these embryos is limited to the mid-sagittal plane using a standard confocal microscope. This aspect of imaging limits the depth of imaging in older embryos and adults, but more advanced multi-photon microscopy systems allow for imaging at greater depths. 3. Significance with respect to existing methods This protocol provides an approach to the analysis of blood vessel networks on a systems level that can incorporate an entire animal. Earlier representations of such data often relied on series of images laid out together, but 3D rendering provides better resolution of the spatial relationships involved. 4. Future applications New developments in imaging and tissue processing will provide many new applications for these methods that may include making older embryos or adults transparent11-14.Enhanced transparency will greatly increase tissue penetration by confocal and multi-photon lasers. Further, as the speed of cameras and photomultiplier tubes increase it may soon be possible to produce 3D renderings of fish in real-time, providing a 4th dimension of analysis. 5. Critical steps A critical step in this protocol is preparation for imaging, which includes proper fixation. Imaging should be done as soon as possible after fixation with high quality objectives that have the best numeric apertures available. Resolution depends on the imaging system used, so high quality systems are generally better. Generating 3D renderings is memory intensive for so newer, high-end computers with a large amount of memory and good graphics processors are recommended. The visual biology system described here has been optimized for transgenic zebrafish that express EGFP in vascular endothelial cells, though these methods can be adapted to transgenic embryos that express GFP, or other fluorescent proteins, in populations of neurons, muscles, glands or any number of other cells. The major advantage in working with this system is the ability to study what is happening in the entire embryo at any time during this developmental period, in fixed and/or live animals. There is nothing to disclose. The authors thank past and present members of our laboratories who helped develop these techniques. Partial funding provided to DE by a grant from the California Institute for Regenerative Medicine/CIRM (RN1-00538). \|N – Phenylthiourea\|\|Alfa Aesar, catalog #41972\|\|0.2 M in E3 buffer, kept at 4 °C\| \|E3 buffer\|\|Sigma\|\|5 mM NaCl, 0.17 mM KCl, 0.33 mM CaCl2, 0.33 mM MgSO4\| \|Confocal microscope\|\|Nikon\|\|D-EclipseC1 on a Nikon TE-2000U\| \|Glass bottom dishes\|\|Mat-Tek\| \|GSI IX/DAPT\|\|N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycinet-butyl ester EMD Biosciences\| \|24 well plates\|\|Becton-Dickinson, cat# 351147\|\|BD Falcon\| \|Transfer pipettes\|\|VWR, cat #414004-001\|\|VWR disposable transfer pipettes\| \|Methyl-cellulose\|\|Alfa Aesar, cat#43146\|\|3% in E3 buffer\| \|NRD 4/6 Fish food\|\|Brine Shrimp Direct\|\|Dried\| \|Brine shrimp\|\|Brine Shrimp Direct\|\|Live\| \|Tungsten wire\|\|Small Parts # TW-016-60\|\|0.016” OD\| \|Tricaine\|\|VWR # 101107-950\|\|Tricaine methanesulfonate 250 mg/L in E3 buffer\| - Staudt, D., Stainier, D. Uncovering the molecular and cellular mechanisms of heart development using the zebrafish. Annu Rev Genet. 46, 397-418 (2012). - Westerfield, M. The Zebrafish Book. University of Oregon Press. (2007). - Schindelin, J., et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 9, 676-682 (2012). - Cameron, D. J., et al. Alzheimer's-related peptide amyloid-β plays a conserved role in angiogenesis. PLoS ONE. 7, (2012). - Cunvong, K., Huffmire, D., Ethell, D. W., Cameron, D. J. Amyloid-β increases capillary bed density in the adult zebrafish retina. Invest Ophthalmol Vis Sci. 54, 1516-1521 (2013). - Jin, S. W., Beis, D., Mitchell, T., Chen, J. N., Stainier, D. Y. Cellular and molecular analyses of vascular tube and lumen formation in zebrafish. Development. 132, 5199-5209 (2005). - Lawrence, C. The husbandry of zebrafish (Danio rerio): a review. Aquaculture. 269, 1-20 (2007). - Hagedorn, M., Kleinhans, F. W., Artemov, D., Pilatus, U. Characterization of a major permeability barrier in the zebrafish embryo. Biol Reprod. 59, 1240-1250 (1998). - Schmid, B., Schindelin, J., Cardona, A., Longair, M., Heisenberg, M. A high-level 3D visualization API for Java and ImageJ. BMC Bioinformatics. 11, 274 (2010). - Opitz, R., et al. Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development. Dev Biol. 372, 203-216 (2012). - Gleave, J. A., et al. Neuroanatomical phenotyping of the mouse brain with three-dimensional autofluorescence imaging. Physiol Genomics. 44, 778-785 (2012). - Chung, K., et al. Structural and molecular interrogation of intact biological systems. Nature. 497, 332-337 (2013). - Markaki, Y., Smeets, D., Cremer, M., Schermelleh, L. Fluorescence in situ hybridization applications for super-resolution 3D structured illumination microscopy. Methods Mol Biol. 950, 43-64 (2013). - Walter, T. J., Sparks, E. E., Huppert, S. S. 3-dimensional resin casting and imaging of mouse portal vein or intrahepatic bile duct system. J Vis Exp. 68, e4272 (2012).	2	17	2	0	0	0	0.574719	2	5,187
ICD-10-CM Code F04 Amnestic disorder due to known physiological condition Billable CodeBillable codes are sufficient justification for admission to an acute care hospital when used a principal diagnosis. Mental Health CodeIndicates that the ICD code is referenced in DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Version 5) F04 is a billable ICD code used to specify a diagnosis of amnestic disorder due to known physiological condition. A 'billable code' is detailed enough to be used to specify a medical diagnosis. The ICD code F04 is used to code Amnesia Amnesia (from Greek, meaning "forgetfulness"; from ἀ- (a-), meaning "without", and μνήσις (mnesis), meaning "memory"), also known as amnesic syndrome, is a deficit in memory caused by brain damage, disease, or psychological trauma. Amnesia can also be caused temporarily by the use of various sedatives and hypnotic drugs. Essentially, amnesia is loss of memory. The memory can be either wholly or partially lost due to the extent of damage that was caused. There are two main types of amnesia: retrograde amnesia and anterograde amnesia. Retrograde amnesia is the inability to retrieve information that was acquired before a particular date, usually the date of an accident or operation. In some cases the memory loss can extend back decades, while in others the person may lose only a few months of memory. Anterograde amnesia is the inability to transfer new information from the short-term store into the long-term store. People with this type of amnesia cannot remember things for long periods of time. These two types are not mutually exclusive. Both can occur within a patient at one time. Case studies, such as that of patient R.B., show that both types of amnesia can occur simultaneously. Case studies also show that amnesia is typically associated with damage to the medial temporal lobe. In addition, specific areas of the hippocampus (the CA1 region) are involved with memory. Research has also shown that when areas of the diencephalon are damaged, amnesia can occur. Recent studies have shown a correlation between deficiency of RbAp48 protein and memory loss. Scientists were able to find that mice with damaged memory have a lower level of RbAp48 protein compared to normal, healthy mice. In people suffering with amnesia, the ability to recall immediate information is still retained, and they may still be able to form new memories. However, a severe reduction in the ability to learn new material and retrieve old information can be observed. Patients can learn new procedural knowledge. In addition, priming (both perceptual and conceptual) can assist amnesiacs in the learning of fresh non-declarative knowledge. Amnesic patients also retain substantial intellectual, linguistic, and social skill despite profound impairments in the ability to recall specific information encountered in prior learning episodes. \|MeSH Codes:\|\|D000647, D000647, D000647\| \|ICD 9 Codes:\|\|294.0, 780.9, 780.93\| Coding Notes for F04 Info for medical coders on how to properly use this ICD-10 code Inclusion TermsInclusion Terms are a list of concepts for which a specific code is used. The list of Inclusion Terms is useful for determining the correct code in some cases, but the list is not necessarily exhaustive. - Korsakov's psychosis or syndrome, nonalcoholic - The underlying physiological condition Code Type-1 Excludes: Type-1 ExcludesType-1 Excludes mean the conditions excluded are mutually exclusive and should never be coded together. Excludes 1 means "do not code here." - Amnesia NOS - instead, use code R41.3 - Anterograde amnesia - instead, use code R41.1 - Dissociative amnesia - instead, use code F44.0 - Retrograde amnesia - instead, use code R41.2 Code Type-2 Excludes: Type-2 ExcludesType-2 Excludes means the excluded conditions are different, although they may appear similar. A patient may have both conditions, but one does not include the other. Excludes 2 means "not coded here." - Alcohol-induced or unspecified Korsakov's syndrome (F10.26, F10.96) - instead, use code F10.26 - Korsakov's syndrome induced by other psychoactive substances (F13.26, F13.96, F19.16, F19.26, F19.96) - instead, use code F13.26 - DRG Group #884 - Organic disturbances and mental retardation. Related Concepts SNOMET-CT - Organic amnesia of language (disorder) Coding Advice SNOMET-CT - Consider additional code to identify specific condition or disease - This is an infectious agent code for use in a secondary position ICD-10-CM Alphabetical Index References for 'F04 - Amnestic disorder due to known physiological condition' The ICD-10-CM Alphabetical Index links the below-listed medical terms to the ICD code F04. Click on any term below to browse the alphabetical index. Equivalent ICD-9 Code GENERAL EQUIVALENCE MAPPINGS (GEM) This is the official approximate match mapping between ICD9 and ICD10, as provided by the General Equivalency mapping crosswalk. This means that while there is no exact mapping between this ICD10 code F04 and a single ICD9 code, 294.0 is an approximate match for comparison and conversion purposes.	4	3	0	0	0	15	0.907193	15	1,206

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