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{
"age": 64,
"case_id": "PMC3420475_01",
"case_text": "A 64-year-old male presented with fatigue, bilateral leg swelling, and a painful lower extremity rash for one month. Examination revealed 1 to 5 millimeter macules that were tender, violaceous, and nonblanching. The patient had no history of recent infections, new medications, or other systemic complaints. Treatment of the rash with topical steroids was not successful.\nComplete blood count, creatinine, liver enzymes, urinalysis, prothrombin time, partial thromboplastin time, thyroid function tests, and lactate dehydrogenase levels were all within normal limits. Hepatitis B and C serologies and human immunodeficiency virus tests were negative. Antinuclear antibodies and subsets, rheumatoid factor, and antineutrophilic cytoplasmic antibodies were negative. Erythrocyte sedimentation rate was 47 mm/hr, C-reactive protein was 1.8 mg/dL, beta-2 microglobulin was 3.1 mg/L (0-3 mg/L), C3 was 139 mg/dL, and C4 was 18.8 mg/dL (20-47 mg/dL). Serum cryoglobulins were present at 14%. Quantitative serum immunoglobulin testing showed an elevated IgM of 1770 mg/dL, and serum viscosity was normal at 1.56. A skin punch biopsy revealed leukocytoclastic vasculitis with cryoglobulin deposits (Figure 1). Computed tomography of the chest, abdomen, and pelvis was normal as was a bone marrow aspirate.\nTreatment for presumed essential mixed cryoglobulinemia with oral prednisone 40 mg and azathioprine 150 mg daily resulted in only a partial response, and attempts at tapering steroids were unsuccessful. The lack of response after two months of therapy prompted further testing including a serum protein electrophoresis which revealed an IgM kappa monoclonal gammopathy (0.7 gm/dL). Electrophoresis of the cryoglobulin precipitate was then performed which revealed an IgM kappa monoclonal gammopathy (5.98 gm/dL) consistent with type 1 cryoglobulinemia. At our request, a repeat bone marrow aspiration was performed which demonstrated a 1% abnormal population of monoclonal B cells consistent with early Waldenstrom's macroglobulinemia. Treatment with four weekly doses of rituximab 500 mg IV resulted in a gradual resolution of the rash coupled with a decreased IgM kappa to 0.2 gm/dL within three months, and prednisone was subsequently tapered off.\nAfter six months of remission, macules reappeared on the lower extremities but did not respond to a second course rituximab and steroids. Other unsuccessful therapies included methotrexate, two cycles of bortezomib 1.3 mg/m2 IV, and a combination of melphalan, thalidomide, and prednisone. After being lost to follow up for one year, he was admitted with lower extremity ulcerations secondary to worsening cutaneous vasculitis and received solumedrol 80 mg IV daily plus plasmapheresis. Quantitative cryoglobulins decreased from 17.5% to 2%, and the patient improved clinically. Anticoagulation was also initiated for a right lower extremity deep venous thrombosis. He was readmitted eight months later for infected cutaneous ulcers and severe sepsis that necessitated intravenous antibiotics and surgical debridement. As a result of sepsis, he developed new-onset renal failure requiring chronic dialysis. Presently, the patient continues to receive periodic plasmapheresis for cryoglobulinemic vasculitis.",
"gender": "Male"
}
] |
PMC3420475
|
[
{
"age": 65,
"case_id": "PMC6350017_01",
"case_text": "A 65-year-old male, with a past medical history of glaucoma, cataract, squamous cell carcinoma of the right eyelid, hyperplastic polyp and hyperlipidemia, was diagnosed with Rai stage 0 CLL by absolute monotypic B-cell lymphocytosis >5 x 109/L on normal peripheral flow cytometry, in the year 2000. He did not have any high-risk markers, with CD38 negative disease that showed del 13q on fluorescent in situ hybridization (FISH) and normal beta-2-microglobulin (B2M) as well as lactate dehydrogenase (LDH). He remained asymptomatic and under observation for several years but was noted to have rapidly increasing lymphocytosis, progressive lymphadenopathy, symptomatic splenomegaly and thrombocytopenia in 2015 (Table 1 and Figure 1). Bone marrow biopsy revealed hypercellular marrow with diffuse involvement by lambda light chain-restricted small lymphocytes occupying 95% of the marrow space. First-line treatment was planned with obinutuzumab (1000 mg) and chlorambucil as per standard guidelines but the patient never started chlorambucil due initially to a concern of tumor lysis syndrome from significant disease burden, and later due to development of prolonged neutropenia and thrombocytopenia on obinutuzumab alone. The dose of obinutuzumab was reduced by 20% for cycle 4 and he was given daily G-CSF for three days after the obinutuzumab dose for that cycle only. After completion of six planned cycles of single-agent obinutuzumab, the patient achieved partial response (PR) to therapy as measured by greater than 50% reduction in absolute lymphocyte count (ALC) and splenomegaly as well as a platelet level greater than 100 x 109/L, as per iwCLL guidelines. Disease was detectable as minimal residual disease (MRD) only, by CLL specific MRD peripheral flow cytometry 0.37%, 2 months after completion of treatment, without residual blood, spleen or lymphadenopathy detected. His CLL remained stable over the next 2 years with only slight increase in lymphocytosis. Approximately two-and-a-half years after initial treatment, thrombocytopenia and rapid increase in lymphocytosis were noted (Table 1 and Figure 1).\nA repeat flow cytometry confirmed monoclonal B-cell population along with an upward trending ALC, confirming disease relapse. A repeat FISH once again showed a 13q deletion. Retreatment was initiated due to worsening fatigue and concern for infections as Absolute neutrophil count (ANC) was trending downward. After discussing several treatment options, a shared decision of reintroducing obinutuzumab was taken based on the prolonged initial response of over 2 years with this as a single agent. Lymphocyte count normalized after only one cycle of retreatment and the patient eventually achieved partial response again per the same iwCLL guidelines. Grade 2 IRR was noted at initial treatment but not at retreatment while grade 2 neutropenia and thrombocytopenia were noted at initial as well as retreatment with obinutuzumab. The patient continues to follow up 1 year after the relapse for surveillance and provided informed consent for reporting.",
"gender": "Male"
}
] |
PMC6350017
|
[
{
"age": 7,
"case_id": "PMC4629570_01",
"case_text": "At the Wild Animal Park Planckendael of the Royal Zoological Society of Antwerp, an adult, male Asiatic lion, 2.7 years old, was found dead in his inside enclosure without preceding clinical abnormalities. Gross post-mortem examination revealed a normal body condition with a body weight of 140 kg and the following salient findings: anaemic mucosae; 10 litres of blood in the abdominal cavity; pale-coloured pancreas and spleen; multiple nodular lung masses (a few mm to 10 cm diameter, filled with blood clots) (Fig. 1); multiple (2 mm - 8 mm diameter) kidney cysts (filled with clear transparent liquid); multiple liver nodules (a few mm to 10 cm diameter, filled with blood clots, some with grapelike appearance, others were ruptured) (Fig. 2). An additional macroscopic finding, i.e. an extensive proximal diaphyseal new bone formation on the right humerus, was identified later after the preparation of the skeleton at the Royal Belgian Institute of Natural Sciences in Brussels. No anomalies were detected in any other organ.\nA set of tissue samples (liver, lung, spleen, kidney, bronchial lymph node) was collected and fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned at 4 mum, and stained with haematoxylin and eosin and Prussian blue for histologic examination. Immunohistochemistry was performed on 4-mum sections using Factor VIII-related antigen or von Willebrand factor (vWf) (polyclonal rabbit antibody, reference A0082, Dako, Glostrop, Denmark) and the platelet-endothelial cell adhesion molecule or cluster of differentiation 31 (CD31) (monoclonal mouse antibody, Clone JC70A, reference M0823, Dako, Glostrup, Denmark). External positive controls for the immunohistochemical stainings were spleen from a pig for vWf and mesenteric blood vessels from a dog for CD31. Internal controls consisted of normal endothelial cells in the examined tissues. No non-specific staining was observed in any of the slides.\nIn the liver, there were multifocal areas where the normal architecture was lost and most of the parenchyma had been replaced by non-encapsulated, poorly demarcated, infiltrative and moderately cellular masses. The masses were composed of loosely arranged streams and poorly defined capillary-like channels, supported by a moderate amount of eosinophilic stroma and occasionally large vascular channels, filled with variable amounts of blood (Fig. 3a). Neoplastic cells were mainly polygonal to spindle shaped, with indistinct cell borders, moderate amounts of eosinophilic cytoplasm with a round to oval, centrally placed nucleus with a finely stippled chromatin pattern and 1 nucleolus. There was moderate anisokaryosis and anisocytosis. Mitotic figures ranged from 1 to 4 per high power field. There were larger areas of haemorrhage and necrosis. The neoplastic cells labelled strongly positive for vWf and CD31 (Fig. 3b). In the lung similar neoplastic foci were observed, which also labelled positive for vWf and CD31. There was mild fibrosis of the renal capsule. There were no neoplastic lesions in the kidney. The capsule of the spleen showed focal mesothelial cell proliferation without signs of neoplastic masses in the spleen. In the bronchial lymph node, and especially in its subcapsular sinuses, there was a multifocal mild infiltration of macrophages. Many of those macrophages had an intracytoplasmic accumulation of a yellowish-brown granular pigment. Prussian blue staining confirmed the pigment as haemosiderin. Other macrophages showed erythrophagocytosis. The lesion in the humerus, detected during the preparation of the skeleton, was not examined histopathologically.\nTissue impression smears of bronchial lymph node, liver, lung and also of the abdominal blood were made for bacteriological examinations. Giemsa stain, Gram stain and Ziehl-Neelsen stain were all negative. Cultivation on tryptone-soya-agar and blood agar demonstrated no growth of bacteria.",
"gender": "Male"
}
] |
PMC4629570
|
[
{
"age": 30,
"case_id": "PMC10352529_01",
"case_text": "A woman about 30 years old, with no systematic health issues and non-smoker, consulted the Odontology Department of University Hospital Center of Montpellier (Montpellier, France) to manage aesthetic damages due to congenital missing lateral incisors. After being well informed of every alternative treatment, the patient consented to be treated with an orthodontic treatment associated with delayed implant fixed crowns and provided written informed consent.\nTreatment initially involved mesializing the canines to open up the spaces and reshaping the cuspids with ameloplastia. The choice of opening spaces was required after an accurate clinical radiographic analysis. Indeed, the patient presented several diastemas as well as a mesioposition of canines before orthodontic treatment (Figure 1). In addition, the patient had asymmetry in her wisdom teeth with agenesis of tooth number 16, therefore, excluding the possibility of mesialising molars (Figure 2). Finally, the cephalometric analysis showed a skeletal Class III (angle ANB = 1 ) as well as a normodivergence with a tendency to hypodivergence (angle FMA = 23 ) (Figure 3). Because of the sagittal skeletal relationships, the solution of opening spaces was selected. Mediation of the canines in place of lateral incisors was performed, and canines were rehabilitated with implants. This solution does not accentuate the negative overjet already present in Class III patients. A 2-year multibracket orthodontic treatment in the vestibule area closed the diastemas by repositioning the incisors with maximum bimaxillary anchorage.\nAt the end of the orthodontic treatment, prosthetic and bone spaces were sufficient for the placement of 6 and 11 implants. A subtractive coronoplasty was realized to make up the canines as lateral incisors. During this treatment, lingual rehabilitation was performed to perpetuate the results. Ultimately, a retention was performed to maintain the spaces before the implants were placed. At the end of the orthodontic treatment, patient was addressed to the Implantology Department to restore edentulous spaces with implant-supported crowns.\nUpon extraoral examination, the patient presented an average smile line with visibility of her interdental papilla and partial edentulous spaces in canine area (Figure 4).\nOn intraoral examination, a healthy periodontal status with a thick maxillary phenotype presenting gingival pigmentations was observed. Restorative spaces were about 7.5 mm and were maintained with fixed retainers and maxillary removable resin injected retainer in canine area (Figure 5).\nRegarding the panoramic radiography realized at the end of the orthodontic treatment, canines' root axes were divergent, reducing mesiodistal bone space. But root axes were parallel to bicuspid ones, making the implant placement easier (Figure 6).\nA pre-operative computed tomography was performed to analyze ridge dimensions for implant placement surgery. The mesiodistal bone spaces were about 7 mm in canine position 6 and 6 mm in position 11. On both sides, alveolar crest was narrow (7 mm) and presented a buccal undercut (Figure 7).\nThe patient, with no contraindications to surgery, was informed that a ridge augmentation could be necessary during the surgical phase to avoid vestibular fenestration, and narrow implants have been chosen to fit the ridge width and maintain a minimum of 1.5 mm peripheric bone around implant.\nImpressions of the maxilla and mandible with irreversible hydrocolloid (Alginoplast , Kulzer Mitsu Chemicals Groups, Hanau, Germany) were practiced, and the diagnostic setup for the final restoration was made in order to prepare a composite injected resin tray as interim restoration (Figure 8). Careful attention was taken to maintain space between gingiva and tray, in order to avoid healing interactions.\nDuring surgery, full thickness flap was raised, and two implants were placed with an insertion torque of more than 30 N cm (3.1 x 10 mm; Eztetic , Zimmer Biomet, Palm Beach Gardens, FL, USA) on the region of teeth numbers 6 and 11. Because of the underestimated alveolar ridge dimension visualized on the computed tomography, guided bone regenerations were not indicated and vestibular fenestration have been avoided. Surgical healing screw (CCNSP, Zimmer Biomet, Palm Beach Gardens, FL, USA) was placed on each implant, and operative sites were primarily closed using resorbable sutures 4.0 (Vicryl , Ethicon) (Figure 9).\nResin tray immediate interim rehabilitation was placed to ensure patient's cosmetic satisfaction and maintain edentulous space during early healing process (D + 15). After that, a removable partial denture was placed for 3 months, until osseointegration.\nMucogingival management during second stage implant surgery was performed after osseointegration, and healing collars were placed at the same time (CHCNP33, Zimmer Biomet, Palm Beach Gardens, FL, USA).\nBecause of a lack of keratinized tissue (KT) around implant number 6, a connective tissue graft using envelope flap technique was performed in this site using crestal harvesting to avoid changing gingival pigmentations (Figures 10 and 11).\nIn implant site number 11, a simple incision allowed the placement of the healing collar. The two surgeries were practiced at the same time, and control visits were realized at 2 weeks and 3 weeks (Figures 11, 12, and 13).\nAt D + 21 after second stage implant surgery, the maxilla was impressed using open-tray procedure and dual-mix technique with silicones of different viscosities. First, healing collars were removed, and direct transfers were placed using retaining screw (CHCNP33, Zimmer Biomet, Palm Beach Gardens, FL, USA). Then, light silicone was charged around transfers, and a tray filled with heavy silicone was inserted in the upper jaw. After impression time, transfers were unscrewed and trial disinserted. Finally, implant analogs (CIANP, Zimmer Biomet, Palm Beach Gardens, FL, USA) were screwed to direct transfers into the impression. The mandible impression was classically realized with irreversible hydrocolloid (Alginoplast , Kulzer Mitsu Chemicals Groups, Hanau, Germany). Occlusion cire and teeth color were finally recorded, and information were sent to the laboratory.\nTemporary implant directly fixed crows were tried, and occlusion was adjusted in order to obtain canine guidance in lateral movement but no interdental contact in static occlusion (Figure 14). With these temporary crowns, patient had function and aesthetic rehabilitation, and profile emergence was modeled with resin adjunction for the future definitive crowns (Figure 15).\nAfter orthodontic treatment, the patient was complaining about teeth color, with a \"yellow\" aspect. A step of at-home tooth bleaching was performed between temporary and definitive restoration and using 10% carbamide peroxide with adaptable trays (Polanight , SDI).\nTeeth color was visually measured by the patient and clinicians: the initial teeth color was 3M2 (Figure 16) and after 7 days of overnight at-home bleaching, the final teeth color was 2M2 (Vita 3D-Master , Vita) (Figure 17). Patient was satisfied by the aspect of her teeth, more luminous and less saturated. The bleaching treatment was continued for one more week, and tint stabilization was reached at 1 month, allowing final implant fixed restoration in positions 6 and 11.\nOnce soft tissue has matured and teeth color was stabilized, final implant fixed crowns have been realized. Impression technique was similar to the interim phase except the first step. In fact, a record of the emergence profile was made using flowable resin on the direct transfer (Figure 18).\nDue to the available prosthetic height, individualized milled direct-implant frameworks were made (Zfx, Germany, company of the ZimVie Group) (Figure 19). They allow better management of the emergence profile and passivity, compared to a conventional cast framework or standardized abutment. The coping and the implant abutment are then one piece, reducing the risk of gaps between the different components.\nThe crowns were tried before finishing to check the emergence profile, interdental contact points, static and dynamic occlusions, and ceramic color (2M2 using Vita 3D-Master , Vita) (Figure 20). When placing the direct-implant crowns, all previous points were checked, and crowns were then screwed with an insertion torque equal to 30 N cm (Figures 21 and 22).\nThe patient was satisfied with this rehabilitation, both from a functional and aesthetic point of view.\nControls were realized at 2 weeks and 1 month in order to check occlusion, insertion torque, plaque index, and patient comfort. All static occlusion contacts were deleted on implant fixed crowns, and canine guidance was carefully calibrated in lateral movements.\nCalibrated interdental toothbrushes were prescribed in order to control plaque around implant-supported crown, especially in distal of crown in position 6.\nA 1-year follow-up showed a total integration of crowns with profile emergence and volume apical to crowns fitting natural adjacent structures (Figure 23).\nPatient was completely satisfied by the aesthetic and smile results (Figure 24).\nIn the future, regular follow-up examinations will be carried out to ensure good tissue integration, proper plaque control, and peri-implant health.",
"gender": "Female"
}
] |
PMC10352529
|
[
{
"age": 5,
"case_id": "PMC5228701_01",
"case_text": "We present the case of a 5 years and 9-month-old female patient, who was admitted in our clinic for inferior limb pain and painful edema of the right index finger. The anamnesis revealed that the patient's mother had complained of joint pain during childhood, and she was diagnosed with acute articular rheumatism. The patient's personal history underlined that she had complained of inferior limb pain for approximately 1 year, but in the last month she associated painful edema of the right index finger, therefore she was referred to a pediatric surgeon, who suspected a proximal interphalangeal subjoint dislocation and requested a hand X-ray. The X-ray showed 2 opaque lesions in the right radial metaphysis, therefore she was admitted in our clinic for further investigations.\nThe clinical exam performed at the moment of admission revealed the following pathological elements: weight and height deficit, W: 17.6 kg (-0.88 SD), H: 109.5 cm (-1.02 SD), BMI: 14.7 (-0.78 SD), deformity of the proximal interphalangeal joint of the right index finger (Fig. 1), abnormal position of the inferior limbs (genu valgum), and bilateral flat feet.\nThe laboratory test performed during admission, namely CBC count, transaminases, immunity status (IgA, IgM, and IgG) tests, peripheral smear, but also thyroid hormones, rheumatoid factor, antistreptolysin O titer, anticitrulinated protein antibodies, antinuclear antibodies, circulating immune complexes, parathormone, and serum phosphorus, were all within normal limits. The X-ray of inferior limbs revealed multiple metaphyseal osteochondromas of the distal femur, proximal tibia, and fibula of the 3rd right metatarsal bone, and proximal and medial phalanges of the 2nd, 3rd. and 4th right toes (Fig. 2, 3 and 4).\nWe also performed a thorax and a spinal column X-ray, but no pathological aspects were identified. We referred the patient to an endocrinologist, but both clinical and ultrasound exams of the thyroid gland were normal. We also requested a genetic consultation, and the genetics specialist suggested a radiological investigation of parents and also periodic radiological assessment of bone lesions with pediatric monitoring.\nBased on all these clinical and radiologic findings, we established the diagnosis of multiple osteochondromas.\nWe assessed both parents radiologically in order to identify a possible hereditary transmission of these bone tumors. The mother X-rays revealed multiple osteochondromas of the left radius, bilateral femur, tibia, and peroneus, and also bilateral metatarsals.\nTherefore, the final diagnosis was of HME.\nWe discharged the patient with the recommendation of radiological monitoring at least once a year or if any clinical sign of complications appears, taking under consideration the risk of malignant transformation. The radiological aspect at 6 month follow-up did not reveal any additional modifications.",
"gender": "Female"
}
] |
PMC5228701
|
[
{
"age": 28,
"case_id": "PMC5139886_01",
"case_text": "A 28 year old, healthy Thai male, employed in Israel as an agricultural worker, presented to the emergency room with complaints of nausea, vomiting and diffuse abdominal pain starting 3 days earlier. Past medical history was unremarkable and without mention of recent illness. On presentation, the patient was well oriented in no severe distress, physical examination was notable for epigastric tenderness with guarding. Heart rate was 116 beats/minute, blood pressure 94/59 mm/Hg and a temperature of 37.4 C. The patient was admitted to the surgical department for evaluation. A chest and abdomen CT revealed marked liver enlargement with fatty change, and minimal amounts of pleural and pericardial fluid. No surgical etiology was recognized and due to laboratory findings of renal failure (Creatinine 3.88 mg/dl BUN 119.7 mg/dl), the patient was transferred to the medical department.\nShortly after arrival, the patient's condition deteriorated rapidly to a state of agitation and shock and he was transferred to the intensive care unit. On arrival blood pressure measured 79/45 mm/Hg, pulse 170 beats/minute with episodes of SVT. In addition, the patient developed dyspnea, with a respiratory rate of 48 breaths/minute and anuria. Core temperature measured 33.1 C. Examination revealed marked peripheral cyanosis, distended jugular veins with cool extremities. Air entry to both lungs was reduced and palpation of the abdomen was noted for tenderness and an enlarged liver. Laboratory analysis showed lactic acidosis (pH 7.22, lactate 129 mg/dl), renal failure (creatinine 2.11 mg/dl), and rhabdomyolysis (CPK 3,205 IU/l). Liver function tests and coagulation indices were also disturbed ( total bilirubin 2.74, direct bilirubin 1.03 mg/dl, AST 1169 IU/l, ALT 890 IU/l, LDH 1743 IU/l, INR 1.7, factor V level 18%,). Erythrocyte sedimentation rate was within normal limits. Factor V levels continued to decline to a nadir of 5%. The above laboratory results, in combination with encephalopathy, indicated fulminant hepatic failure accompanied by multi-system organ failure.\nThe patient failed a trial of positive pressure ventilation and was subsequently intubated and ventilated mechanically. A Swan-Ganz catheter was inserted and fluid resuscitation started, steroids and vasopressors were given. Echocardiography was used to rule out pericardial tamponade; normal ventricular and valvular function was demonstrated. Continuous hemodiafiltration was started and switched to standard hemodialysis a week later. A tracheotomy was later performed due to the need for prolonged ventilation. Blood, urine, sputum and peritoneal fluid aspirate were cultured and gram and Ziell-Nielsen stained. Empiric antibiotic therapy was then started. Culture results were negative. Serologic testing for acute or chronic infection with viral hepatitis types A, B and C, HIV, Epstein-Barr virus, Cytomegalovirus returned negative. Further serologic testing for Ricketsia conorii, Coxiella burnetii were also negative. A thick film smear for blood-borne parasites and stool collection for ova and parasites were negative. Due to a high osmolar gap, levels of methanol, ethylene glycol and acetyl salicylic acid were checked and no traces were found.\nA health bureau inspector was sent to the residence of the patient and found a stock of canned food the patient consumed almost exclusively for a period of months. Specimens were examined at the ministry of health. AFB1 was found at a level of 19.6 ppb (allowed level < 5 ppb). The patient's condition gradually improved on supportive treatment. Vasopressors were stopped and dialysis discontinued after blood pressure, renal function and CPK values returned to normal. Liver function tests improved markedly. After 21 days of mechanical ventilation the patient was weaned and the tracheotomy closed on the 36th day. The patient was returned to the medical department for observation and physiotherapy. No apparent sequels were observed other than mild residual hypertension. The patient was discharged on day 45.",
"gender": "Male"
}
] |
PMC5139886
|
[
{
"age": null,
"case_id": "PMC4303471_01",
"case_text": "The proband first came to medical attention at one month of age when, after an uneventful gestation and delivery, he was noted to have abnormal movements characterized as myoclonic seizures. Over the ensuing months, seizures evolved to consist of both generalized tonic clonic and myoclonic events, with frequent status epilepticus, which was exacerbated by febrile events, resulting in several dozen hospitalizations. Seizures are now better controlled, but on a regimen of Oxcarbazepine, Topiramate, Levetiracetam and Zonisamide. At approximately two years of age, the patient developed truncal and head titubation and adventitious movements characterized as choreathetoid, which intruded on sleep and residual neurologic function. Upon initial observation and subsequently, the patient showed no evidence of dysmorphic facies, though he was microcephalic (orbitofrontal head circumference >2 standard deviations below the mean). The patient has also suffered from severe developmental stagnation and now, at age 10 years, is able to only minimally communicate with his care providers, is unable to sit or walk and does not have any self-help skills. Neuroimaging, first obtained at several months of age, and repeated serially over the course of his care, showed an initial severe deficit in the development of age appropriate myelination that has never normalized. Indeed, the most recent MRI, performed at 7 years of age, has shown evidence of progression of myelination but at levels that are still severely reduced (Figure 1A-C), consistent with severely delayed myelination.\nElectroencephalogram telemetry done at age two years was characterized by high voltage background slowing (delta range, 0.5-2.5 Hz) and superimposed multifocal interictal sharp discharges with occasional periods of burst-suppression. Habitual clinical events were recorded as myoclonias involving the extremities with associated oral dyskinesias followed by a motionless appearance, without changes in the electrographic background, most consistent with subcortical events. Subsequent EEGs have continued to show an absence of normal background organization with multifocal epileptiform discharges during wakefulness and with activation in sleep, although without ictal events (Figure 1D).\nThe patient's seizures were refractory to medical management until approximately 7 years of age when the patient was placed on multiple anticonvulsants, at which point they became infrequent. The underlying cause of the seizures and delayed myelination, however, remained enigmatic. Extensive biochemical and genetic testing revealed no abnormalities other than mildly increased levels of sialic acid in the CSF and urine, and subsequent fibroblast and genetic studies of sialic acid metabolism were unremarkable.\nThe patient's presentation and severely delayed myelination were consistent with an inherited leukoencephalopathy, and he was therefore enrolled prospectively in a Myelin Disorders Bioregistry Project study on unclassified leukoencephalopathies at Children's National Medical Center (CNMC). To investigate the possible genetic origin of the patient's disease we performed whole exome sequencing on DNA collected from the proband and the unaffected parents. We produced > 19 Gb of sequence for each individual, yielding a mean depth of 57 fold coverage with an average 90.4% of target bases sequenced at least 18 times. Using a custom-developed pipeline that integrates parental variant calls into the analysis of the affected child, a heterozygous de novo mutation in KCNT1 (MIM 608167; NM_020822.2) was identified in the proband (NM_020822: c.2794T>A, p.F932I; Figure 1E). Sanger sequencing of the trio confirmed that this mutation was specific to the patient, and further analysis showed that it is not present in dbSNP135, the 1000 Genomes Project database or the NHLBI Exome Sequencing Project database. This was the only de novo mutation identified in this screen that passed our filtering criteria. KCNT1 p.F932 is highly conserved (phyloP score of 0.989744), and the p.F932I change is, in principle, the most damaging non-synonymous change found in our screen, with a PolyPhen2 score of 0.998, a SIFT score of 0.99, and MutationTaster score of 0.78.",
"gender": "Male"
}
] |
PMC4303471
|
[
{
"age": 57,
"case_id": "PMC5012799_01",
"case_text": "A 57-year-old female, with a history of severe hypertension presented with interscapular pain with a sudden onset. On physical examination, she had a high blood pressure 220/120. On electrocardiogram there was a sinus rhythm with a left ventricular hypertrophy. Initial non-contrast CT and transoesophagel echography (TEE) (Figure 1) showed a Stanford type B hematoma formation in the descending thoracic aorta with internal deviation of intimal calcification. Two weeks later, after blood pressure stabilization, a control CT scan and TEE (Figure 2 A, B) revealed ULP, appearing as an intimal tear, with a reperfusion area in the hematoma. Contrast CT scan showed the importance of the reperfusion area (Figure 2 C). On the 3 months follow up contrast CT scan (Figure 3), there was no aortic dissection or aneurysm. The hematoma was stable with an ectasic aorta.",
"gender": "Female"
}
] |
PMC5012799
|
[
{
"age": 56,
"case_id": "PMC4049038_01",
"case_text": "We present a case of a 56-year-old right-hand dominant builder. He gave a weeks' history of worsening pain around his right shoulder joint. There was no history of trauma or injection. He had been feeling feverish and also had complained of a sore throat a few weeks previously. His past medical history included diverticular disease and osteoarthritis of the right knee. He had no history of being immunocompromised. He was HIV negative and did not have diabetes.\nOn examination, the patient held the right shoulder in internal rotation. No active movement was possible and any attempted passive movement was significantly uncomfortable. The overlying skin displayed no cellulitis, erythema or puncture wounds. Palpation did not reveal any obvious subcutaneous collections, and there was no neurovascular deficit. The shoulder area was globally very tender to touch.\nThe patient demonstrated signs of systemic sepsis with a tachycardia and a temperature of 39.1 C. Hematological and biochemical investigation revealed an elevated white cell count at 13.88 x 109 /L (normal range: 4.00-10.00 x 109 /L), as well as a raised C-reactive protein at 267 mg/L (normal range: Less than 5 mg/L) .\nShoulder radiographs were unremarkable. Both anterior and posterior glenohumeral joint aspirations were performed in the emergency department which produced a small amount of turbid fluid which was initially thought to have come from the joint. It is possible that this had penetrated the abscess in the deltoid which was to be discovered later. Microscopy of the aspirate demonstrated numerous white cells but no organisms were seen on Gram stain. No bacterial growth was identified after 40 h of incubation. The patient was commenced on intravenous flucloxacillin for a presumed native joint septic arthritis.\nAn ultrasound of the right shoulder was performed which failed to identify any significant intra-articular effusion. An MRI scan of the shoulder girdle demonstrated a moderate joint effusion, extensive swelling and abnormal signal within the subscapularis and teres minor [Figures 1 and 2]. The initial suspicion was of septic arthritis.\nA posterior portal arthroscopic washout the shoulder was subsequently performed. A moderate amount of turbid fluid was discovered and multiple samples were sent. The joint was irrigated until clear with 6 L of saline. The immediate Gram stain of the turbid fluid failed to identify any bacteria.\nFurther surgical exploration was undertaken 3 days later because of poor clinical response. The lack of specific clinical signs made this clinical decision difficult. A posterior abscess could not be excluded. A deltopectoral approach was performed. No clear edema was encountered down to subscapularis. A subscapularis split failed to show pus in the joint. A finger sweeping under deltoid (laterally and posteriorly) opened an abscess which drained 500 mls of foul smelling, dark green pus. A large cavity of pus was identified between infraspinatus, teres minor and deltoid. Multiple samples were again taken. One was referred for 16s rRNA PCR.\nA further debridement was undertaken 3 days later. The shoulder was approached posteriorly and pus was identified between the deltoid and infraspinatus muscle bellies. The anterior incision was also re-opened and further pus drained. The posterior and lateral deltoid was necrotic and was resected. Again multiple biopsies, including both muscle and fat were sent for analysis. The antibiotic regimen was modified to intravenous piperacillin/tazobactam, however, shortly afterwards the specimen from the third surgical washout grew mixed anaerobes. Antibiotics were changed accordingly to gentamicin and then further to metronidazole and ciprofloxacin when sensitivities were available. Shortly afterwards the 16s rRNA PCR identified a mixed trace with fusobacterium species and Prevotella species. This suggested a primary upper airway focus.\nThe patient's inflammatory makers transiently improved and then deteriorated once again. A repeat MRI scan was performed to ensure no other source of infection. It demonstrated no significant deterioration in the joint since open surgery. There was a small amount of joint fluid but no significant effusion. However, there was gross deterioration and swelling in the appearances of the surrounding musculature with gas and fluid in the soft tissues. This was highly suggestive of a rapidly progressive soft tissue infection. A fourth open debridement of the right deltoid area was undertaken on day 16 for failure of the inflammatory markers to improve. Pus was again identified and mixed anaerobes grown. Thorough debridement was carried out on the first episode so the re-accumulation was surprising.\nThe reason for recurrence was investigated. In order to exclude causes of an impaired immune response, a global immune screen, in addition to HIV and diabetes testing, was performed. It is of note that he was investigated with a CT on admission that showed no obvious collection making seeding from diverticulitis unlikely. It is postulated that, given his upper airway viral prodrome and the causative organism that this gentleman had a rare complication of Lemierre's syndrome.\nHe was discharged on ciprofloxacin and reviewed at day 14 and day 21 after discharge. At both points he remained well and his inflammatory markers remained normal. At 6 months he remained systemically well and had full range of movement in his right shoulder.",
"gender": "Male"
}
] |
PMC4049038
|
[
{
"age": 71,
"case_id": "PMC6395856_01",
"case_text": "A 71-year-old woman presented with a chest computed tomography (CT) finding of left upper (Fig. 1A) and right lower (Fig. 1B) lung field nodules. Left upper lung field nodule was diagnosed by endobronchial ultrasound with a guide sheath as squamous cell carcinoma with high programmed death-ligand 1 (PD-L1) expression (70%) (Fig. 2A). 18F-fluoro-2-deoxyglucose positron emission tomography showed uptake in both nodules. The cancer stage was determined as cT3N0M1a. After 13 cycles of pembrolizumab every 3 weeks, chest CT revealed a dramatic decrease in the size of the lesion in the left upper lobe (Fig. 1C), but the size of the lesion in the right lower lobe was significantly increased (Fig. 1D). Because the treatment effect differed between the bilateral lung lesions, a definitive right lower lung nodule diagnosis was obtained with CT-guided transthoracic needle biopsy (CTNB) (Fig. 2B).\nSamples were obtained from the right lower lesion by CTNB. Pathological findings revealed squamous cell carcinoma with nonexpression of PD-L1. Therefore, treatment of the right lower nodule was ineffective because of PD-L1 nonexpression. Following discussion with the cancer board, right lower lobectomy was recommended.\nHowever, although surgery was recommended in this case, the patient's bronchial asthma was severe. She had with a history of refractory asthma for approximately 20 years. She was treated with ICS, long-acting beta-agonists (LABA), long-acting muscarinic antagonists, and antiallergic drug therapy. She was occasionally treated with oral or systemic corticosteroids for exertional dyspnea.\nThese treatments were all determined to be insufficient if the patient was to undergo lung surgery. On physical examination, her peripheral arterial blood oxygen saturation was 95% in room air, but chest auscultation revealed diffuse expiratory wheezing. The maximum blood eosinophil count was 680/muL. The forced expiratory volume in 1.0 second (FEV1) was 1280 mL (%FEV1, 76.3%), vital capacity (VC) was 2080 mL (%VC, 94.8%), and peak flow was 196 L/min in a pulmonary function test.\nBenralizumab was administered before surgery. No adverse events occurred. Two days after benralizumab administration, her asthma symptoms (wheezing, cough, and dyspnea) disappeared. Pulmonary function tests and eosinophil count were performed again 4 days after benralizumab administration. Her peak flow was improved from 196 to 210 L/min, and her eosinophil count was reduced to 0/muL. Surgical resection by video-assisted thoracic surgery was performed 5 days after benralizumab administration. The eosinophil count in surgical tissue was markedly reduced compared with that in preoperative CTNB tissue (Fig. 3A and B). No severe asthma attacks occurred after surgical resection and benralizumab administration, and the patient was discharged from the hospital. Respiratory function tests 6 weeks after surgery showed FEV1 of 1120 mL (%FEV1, 70.9%), VC of 1740 mL (%VC, 80.0%), and peak flow of 240 L/min. The patient was administered benralizumab continuously after surgery, and no asthma attacks or cancer recurrence occurred for 6 months after surgery.",
"gender": "Female"
}
] |
PMC6395856
|
[
{
"age": 0,
"case_id": "PMC3401649_01",
"case_text": "A young nine-month-old boy of Asian origin presented to our hospital with 1 day history of mild temperature, vomiting, and coryzal symptoms. He was born out of nonconsanguineous marriage and is the only child of his parents. He had a normal birth and development, and was up to date with his immunizations. There was no family history of any serious neurological conditions or strokes. On initial examination his temperature was 38.5 C and heart rate of 100 beats per minute. Hydration was normal. He was noted to be very pale and had a systolic murmur over the precordium. Liver was 1 cm below the costal margin with no other masses palpable.\nLaboratory investigations showed that his hemoglobin (Hb) was 4.1 g/l, platelets 866, white cell count 14, mean corpuscular volume (MCV) 48, mean corpuscular hemoglobin (MCH) 11, reticulocyte count 22, and total iron of 7 mug/l. Liver functions, renal profile, and C reactive protein were normal. His urine was clear. Chest X ray was unremarkable with no cardiomegaly. Blood film demonstrated severe microcytosis and \"pencil cells.\" Hemoglobin electrophoresis showed Hb A2 of 2.2% and Hb F 1.7%.\nChild was admitted due to severe anemia and started on oral Iron. He developed mild diarrhea over the next few days which completely settled. Blood transfusion was not required and he was never unwell or in cardiac failure. After 7 days of hospitalization, he suddenly became drowsy and encephalopathic with GCS of 9/15. Urgent CT scan of his brain showed extensive cerebral sinus thrombosis with venous infarction. MRI brain demonstrated bilateral thalamic infarction with hemorrhagic transformation. MR Venogram (MRV) confirmed extensive thrombosis of internal cerebral vein, vein of Galen, straight sinus, sigmoid sinus, and basal vein of Rosenthal [Figure 1].\nHe was started on low molecular weight heparin (LMWH). He later developed mild left hemiparesis which resolved within days. Repeat CT brain did not show any extension or new hemorrhage. Cardiac echogram was normal. He remained well and was discharged from the hospital with no focal deficit.\nRepeat MRI after 3 months showed partial recanalization of venous sinuses. Neurologically he has remained well and his development is normal. Extensive investigations to determine any other underlying prothrombotic disorder were negative.",
"gender": "Male"
}
] |
PMC3401649
|
[
{
"age": 57,
"case_id": "PMC6243306_01",
"case_text": "A 57-year-old female visited a nearby clinic with a chief complaint of sharp pain and taut skin in the left breast. After examination, the lesion was diagnosed as primary breast cancer (invasive carcinoma of no special type), which was immunohistochemically negative for oestrogen receptor, androgen receptor and human epidermal growth factor receptor Type 2. The cancer clinical stage was T4bN1M0 Stage IIIB (Union for International Cancer Control guidelines). Neoadjuvant systemic chemotherapy together with mastectomy was recommended as a therapeutic option. However, she refused all treatment and left the lesion untreated for approximately 10 months. When the tumour increased in size and the pain became intolerable, she expressed a strong desire to receive minimally invasive treatment, such as TACE. Thus, she was referred to our clinic.",
"gender": "Female"
}
] |
PMC6243306
|
[
{
"age": 34,
"case_id": "PMC6900946_01",
"case_text": "In July 2012, a 34-year-old man presented to the Emergency Department with a 4-month history of headaches, paroxysmal vertigo, nausea, and photophobia, with acute worsening of symptoms over the previous week. His past medical history was unremarkable, and there was no significant family history or any occupational exposure potentially associated with sarcoma. Figure 1 provides a timeline of events including diagnostic assessments and interventions. Computed tomography (CT) and magnetic resonance imaging (MRI) of the brain demonstrated a 2.4 x 2.5 cm mass in the right lateral to midtemporal lobe and associated area of hemorrhage (Figures 2(a) and 2(e)). Dexamethasone was prescribed for cerebral edema and levetiracetam for seizure prophylaxis. A subtotal resection was achieved using a right temporal craniotomy and stealth-guided tumor resection. Pathologic review identified a WHO Grade II Astrocytoma (Figure 2(i)). The patient was treated with localized radiation therapy (RT) with 5040 cGy which was well-tolerated. No chemotherapy regimen was started at this time.\nRepeated MRI at 4 and 5 months after completion of RT showed a growing nodule of contrast enhancement in the right frontal lobe and associated vasogenic edema despite dexamethasone treatment (Figure 2(b)). MRI perfusion studies showed increased blood flow to these new areas (Figure 2(f)), and a second tumor resection was performed. Pathologic assessment revealed a mixture of radiation necrosis and WHO Grade III Astrocytoma (Figure 2(j)) with no isocitrate dehydrogenase (IDH) mutation. The patient began a regimen of temozolomide (cycle 1 : 150 mg/m2, days 1-5 each 28-day cycle; cycle 2 : 175 mg/m2). After two cycles of temozolomide treatment, the patient presented to the Emergency Department with a 1-week history of acute headache, nausea, and vomiting. MRI revealed a 4.4 x 3.5 x 4 cm heterogeneously enhancing mass lesion with perfusion, consistent with progressing tumor. Imaging also showed a significant increase in surrounding vasogenic edema which proved difficult to manage due to increasing complications from dexamethasone treatment, including persistent folliculitis and myopathy.\nThe patient's treatment regimen was changed to bevacizumab (10 mg/kg every 2 weeks) to treat the underlying tumor and vasogenic edema, in an effort to reduce corticosteroid exposure. The patient tolerated 6 cycles of bevacizumab well, and his clinical condition began to improve. However, a follow-up MRI showed increased enhancement of the right frontal lobe mass and new dural-based nodular areas of enhancement (Figure 2(c)). Clinically, the patient appeared to be responding to bevacizumab. As expected, there was reduced cerebral blood flow observed on MRI perfusion; however, the increased enhancement was concerning as this is typically reduced with bevacizumab treatment (Figure 2(g)). An initial concern was there may be dissemination of high-grade glioma. A lumbar puncture was deferred due to mass effect. A biopsy of a right frontal dural-based nodule was pursued, and the pathologic assessment was consistent with a high-grade sarcoma lacking any further differentiating features (Figures 2(k) and 3(a)-3(c)). While the type of sarcoma could not be determined, it was specifically not gliosarcoma. After presentation of the sarcoma, the patient was referred to a genetic counselor with concern for a genetic predisposition (specifically, Li-Fraumeni syndrome). However, genetic testing revealed no pathogenic mutations in the TP53 gene or any other known mutations.\nFurther imaging of the neuroaxis was completed to ensure there was no spread of the sarcoma through the subarachnoid space. MRI of the cervical, thoracic, and lumbar spine showed no areas of abnormal enhancement, and a CT PET of the body revealed no other new hypermetabolic lesions. Multidisciplinary discussions with medical and radiation oncologists ensued regarding the number and spread of the dural-based lesions, and chemotherapy was considered to be the best treatment option for the sarcoma. The patient was started on a regimen consisting of ifosfamide (3750 mg/m2 days 1-2 each 21-day cycle) and doxorubicin (30 mg/m2 days 1-2 each 21-day cycle), continuation of bevacizumab (10 mg/kg every 2 weeks; 4 additional cycles), and initiation of NovoTTF (Optune) treatment for the malignant glioma. The chemotherapy treatment was not well-tolerated, and the treatment course was complicated by neutropenic fever and fatigue despite growth factor support and dose reduction. Thus, the patient only completed 3 cycles. Data from the Optune device showed sporadic use, averaging less than 18 hours per day.\nUltimately, the patient's condition began to further deteriorate. Follow-up MRI revealed an increase in dural-based nodules involving the entire right hemisphere and left cerebellum, as well as an increase in size of the centrally necrotic mass in the right frontal lobe (Figures 2(d) and 2(h)). The recommendation was made to initiate hospice care. The patient received a second opinion at another institution, where he received a gemcitabine/docetaxel regimen, but only completed one dose of gemcitabine due to thrombocytopenia and clinical worsening. The patient received one additional dose of bevacizumab (15 mg/kg). He continued to decline and eventually succumbed to glioma and sarcoma less than 2 years after his initial diagnosis.",
"gender": "Male"
}
] |
PMC6900946
|
[
{
"age": 83,
"case_id": "PMC9539137_01",
"case_text": "An 83-year-old man presented with a 6-month history of dull pain in the right abdomen. Serological examination revealed that he was negative for hepatitis B surface antigen and hepatitis C virus antibodies. On computed tomography examination, irregular and slightly low-density (~26 HU) shadows were observed in the right lobe of the liver, near the top of the diaphragm, representing a tumor measuring 29 x 23 mm with clear boundaries (Figure 1). Serological tests revealed that the patient had a carcinoembryonic antigen level of 5.38 microg/L (normal range, 0-5.0 microg/L), alpha fetoprotein level of 3.36 microg/L (normal range, 0-20 microg/L), carbohydrate antigen 19-9 level of 36.97 micro/ml (normal range, 0-37 micro/ml), and cancer antigen-125 level of 11.42 micro/ml (normal range, 0-35 micro/ml).\nDuring the operation, the tumor was found to be located in the eighth segment of the right lobe of the liver; thus, the right hepatic lobe was partially resected. The tumor was a grayish-yellow mass (2.5 x 2 x 2 cm) located under the liver capsule with a clear boundary from surrounding tissues. Microscopic observation revealed that it was moderately differentiated hepatocellular carcinoma with a cord-like, trabecular structure and a pattern of local pseudoglandular growth. Some tumor cells were translucent, and multiple satellite nodules were found around the main tumor nodule (Figures 2A,B). An area of liver tissue (~0.3 cm) located 0.5 cm from the main tumor had a benign-appearing follicular thyroid structure (Figures 2B,C). The lesion was too small to appear on CT images. The follicles contained colloid tissue and were lined with low cuboidal cells with scant cytoplasm; lymphatic tissue was also present in the area.\nImmunohistochemical (IHC) analysis of the hepatocellular carcinoma revealed hepatocyte antigen positivity, cytokeratin-19 negativity (Figure 2D), and glypican-3 (GPC-3) positivity (Figure 2E). Epithelial cells in the area with a follicular thyroid structure showed no atypia; they were negative for hepatocyte paraffin 1 (Hep Par-1) and positive for thyroglobulin (TG) (Figure 2F), PAX8 (Figure 2G), and thyroid transcription factor-1 (TTF-1; Figure 2H).\nThe patient had no history of a thyroid tumor, and thyroid function test results were normal. Thyroid hormone levels were in normal ranges (triiodothyronine, 1.27 ng/mL; thyroxine, 10.5 g/dl; free triiodothyronine, 3.84 pmol/L; and free thyroxine, 17.76 pmol/L).\nUltrasound examination showed no primary thyroid tumor. The final diagnosis was moderately differentiated hepatocellular carcinoma with heterotopic thyroid tissue in the liver. One month after surgery, all of the patient's serological markers were normal; no tumor recurrence or metastasis has been detected for 7 postoperative months.",
"gender": "Male"
}
] |
PMC9539137
|
[
{
"age": 16,
"case_id": "PMC9271968_01",
"case_text": "Female patient, 16-year-old, single, brown, student, born in rural area of Pernambuco/Brazil, referred to the neurology and neurosurgery service of the Hospital da Restauracao with a history of frontal, pulsing and progressive headache, worsening over weeks, associated with emetic episodes and fever. The condition evolved with progressive growth of a painful, adhered and fibroelastic consistency mass in the central region of the forehead of the skull, eight days before admission. Report of fever stopped two days after admission, with no signs of meningism, rhinorrhea or any focal neurological deficit. No traumatic event, past or recurrence of sinusopathy or other comorbidity that was related. Patient also referred no use of antibiotics. Laboratory tests also did not present alterations of hematimetric indices or inflammatory tests.\nBlood culture was not performed. CT scan of the skull was performed, which showed an expansive hypodense lesion in the frontal region with intracranial extension associated with perilesional edema (Figure 1), and then transferred to the neurosurgery department with suspicion that the identified expansive formation would have neoplastic origin.\nThe patient underwent brain MRI, which revealed an expansive lesion in the frontal subcutaneous tissue, extending through a bone defect in the frontal sinus that communicated with an extra-axial nodular formation with intra-axial component and circumcision edema with important compressive effect, suggesting a complicated PET with concomitant cerebral abscess (Figure 2). Empirical intravenous antibiotic therapy with ceftriaxone (2 g administrated 12 h/12 h) and metronidazole (7,5 mg/kg administrated each 8 h) was initiated, for eight days before the surgery. Intranasal corticosteroid therapy was not prescribed for our patient.\nThe patient was submitted to neurosurgical approach by bicoronal incision and, as cutaneous flap was rebalanced, granulation tissue, bone erosion with dural adhesion and spontaneous extravasation of purulent secretion was identified. Drainage of the abscess by puncture initially. Performed 5 x 5 cm frontal craniotomy resecting the entire osteomyelitis area. Resected the residual abscess and capsule, a fistulous hole (Figure 3B) was verified communicating purulent contents of the frontal sinus with brain abscess. After cranialization of the frontal sinus, evacuation of the subdural empyema and subgaleal abscess, exhaustive cavity washing was performed with 1,500 mL of saline plus gentamicin. Cranial reconstruction performed with autologous bone part, after curettage and drill of the internal eroded plate of the frontal bone flap and resected material (pus, granulation tissue and frontal sinus mucosa) sent for microbiological analysis and culture, but it was not identified any organism's growth. This sterile culture result was probably due to empirical use of preoperative antibiotics, but anaerobic causative agents, destroyed after contact with oxygen, are also a possibility. Similarly, access to histological examination of the frontal sinus mucosa and the granulation tissue collected was not obtained. This type of intervention - surgical approach, associated with antibiotic therapy, was determined based on characteristics such as continuous abscess growth, intracranial mass effect, risk of complications, and neurological deficits.\nThe patient followed a prolonged course of intravenous antibiotic therapy, ceftriaxone, and metronidazole (7 weeks). A new MRI was performed, 28 days after surgery, and showed the surgical a marked reduction of the frontal extra-axial collection. Meningeal thickening and residual frontal abscess surround by perilesional edema were observed, as shown in the pre and postoperative comparative images in Figure 4.\nDue to the significant improvement of our patient condition, she was discharged after 43 days of post-surgical follow-up, with complementary oral antibiotic therapy with ciprofloxacin. It was chosen due to their broad spectrum, low cost, affordability and recommendation by the Hospital Infection Control Committee. The patient was subsequent outpatient follow-up at the service during the first 9 months, in three consultations, with satisfactory clinical, functional, and radiological control. Diagnosis and hospital therapy did not involve an otolaryngologist, but the patient was referred to a professional in the area.",
"gender": "Female"
}
] |
PMC9271968
|
[
{
"age": 0,
"case_id": "PMC7756012_01",
"case_text": "A 32-day-old male with recent diagnosis of X-linked CGD, dihydrorhodamine (DHR) stimulation index (SI) of 1 and known family history (brother with hemizygous mutation in CYBB c.742dupA), developed low-grade temperatures (37.8 C). Laboratory evaluation on day 1 of illness was notable for 8% bands without leukocytosis on complete blood count (CBC). Chest x-ray, urinalysis, blood, and urine cultures were not revealing. Low grade temperatures continued, and on day 4 he had temperature to 38.8 C, associated with leukocytosis 16.4 k/mm, elevated C-reactive protein (CRP) 11.7 mg/dl, and procalcitonin 0.51 ng/ml. He was hyponatremic 133 mEq/L, hypoalbuminemic 2.7 g/dl, and had elevated transaminases (AST 171 U/L, ALT 164 U/L). Infectious evaluation with blood, urine, and cerebral spinal fluid (CSF) cultures and respiratory pathogen panel by PCR were unrevealing. Empiric treatment was initiated with cefepime and ampicillin. On day 8 of illness, leukocyte count (15.6 k/microl) and CRP (21.5 mg/dl) had further increased and bandemia (15%) was noted. Computed tomography (CT) scan was obtained and demonstrated multifocal pulmonary and splenic nodules measuring up to 13 and 8 mm, respectively ( Figures 1A, B ). Biopsy of the right lung lesion was obtained, and antimicrobials were broadened to meropenem, voriconazole, and micafungin. Fungal etiology was suspected, therefore double anti-fungal coverage was used. Over the next day, bilateral lower extremity mottling and right lower extremity edema with delayed capillary refill were noted. Within hours, the patient progressed to cardiac and respiratory failure requiring mechanical ventilation and multiple vasopressors to maintain adequate perfusion. Hydrocortisone was added as well for vasopressor refractory shock. Repeat laboratory evaluation demonstrated cytopenias, elevated transaminases, and coagulopathy compared to less than 24 h prior ( Table 2 ).\nOver the next 24 h, the patient deteriorated rapidly despite broadening anti-microbials to include vancomycin and amphotericin in addition to meropenem and aggressive resuscitation with multiple blood products. A presumptive diagnosis of HLH was considered based on presence of four of eight known criteria ( Table 1 ) and high dose dexamethasone was added to treat his inflammatory response. Despite these efforts, the patient succumbed to multiorgan failure. Blood and tissue biopsy cultures returned post-mortem, yielding Burkholderia cepacia. Autopsy confirmed hemophagocytosis within the spleen, liver, and bone marrow ( Figure 2 ). Post-mortem next generation sequencing ruled out mutations in genes associated with familial HLH.\nA half Seminole Indian, half African American male was diagnosed with X-linked CGD (DHR SI 1, CYBB, c.492delA), after presenting with Burkholderia gladioli cervical lymphadenitis at 16 months of age. At 23 months of age, he presented with fevers, diarrhea, and mild cough. Workup revealed a small perianal fistula and mild splenomegaly with tiny subcentimeter T2 hypointense lesions, consistent with granulomas. A biopsy was deemed not possible due to size and location of lesions. Bronchoscopy was normal while endoscopy and sigmoidoscopy showed moderate inflammation of the colon, consistent with CGD-associated colitis. Bronchoalveolar lavage fluid and blood cultures remained without growth at that time. Patient was empirically treated with meropenem, concurrently treated for Clostridium difficile infection with oral vancomycin, and corticosteroids 1 mg/kg were initiated for treatment of colitis. Fevers improved and he was discharged home to complete 10 days of antibiotic treatment.\nTwo days after discharge, he returned with fevers and abdominal distension. He was empirically treated with meropenem and voriconazole. Imaging of the chest and abdomen revealed hepatosplenomegaly with small ascites ( Figure 1C ). He was found to be anemic (hemoglobin 6.9 g/dl) and given blood transfusion. Because of fever, hepatosplenomegaly, and anemia, a diagnosis of HLH was considered. Hyperferritinemia and hypertriglyceridemia were found so methylprednisolone 2mg/kg and high dose intravenous immunoglobulin (IVIG) 2 gm/kg were initiated. Over the next several days, he developed pancytopenia and liver failure with coagulopathy, liver synthetic dysfunction, and elevated liver enzymes ( Table 2 ). Laboratory evaluation remained consistent with HLH with high ferritin, CXCL9, and elevated soluble IL-2R (CD25) and no source of infection identified on extensive evaluation. Anakinra was added as adjunct therapy. Three weeks after initial presentation, (1,3)-beta-D-glucan assay returned elevated (234 pg/ml) and bronchoalveolar lavage fluid culture from first admission began growing Penicillium sp. Amphotericin B was added for additional fungal coverage. On hospital day 10, he developed acute respiratory distress necessitating intubation; imaging was consistent with diffuse pulmonary hemorrhage. Despite aggressive ventilator management, he ultimately progressed to cardiac arrest and resuscitation efforts were not successful. The parents declined autopsy; no further analysis of genes associated with familial HLH was performed.\nAn 8-week-old Mexican American boy presented with 2 days of fever (39 C) and 1 week of erythematous rash. The patient was admitted for a sepsis-rule out, empirically placed on ampicillin and cefotaxime following CSF, blood, and urine culture collection. All cultures were negative. His past history was remarkable for contracting pertussis at 10 days of life for which he was treated without complications.\nDespite antimicrobial therapy, while still hospitalized, his fevers (38.5-40 C) continued and he developed leukopenia, neutropenia, and anemia. His clinical course further deteriorated with the development of seizures; ceftriaxone and vancomycin were added for empiric meningitis coverage. Hepatosplenomegaly was noted on physical exam and a diagnosis of HLH was considered. Laboratory evaluation showed hyperferrtinemia, hypertriglyceridemia, hypofibrinogenemia, and elevated soluble IL2R level, all consistent with HLH ( Tables 1 and 2 ). Perforin expression was normal and NK cell function was inconclusive due to an inadequate sample. A bone marrow biopsy revealed increased histiocyte number with evident hemophagocytosis. HLH treatment was initiated with dexamethasone, cyclosporine, and IVIG. The patient received 8 weeks of therapy and ultimately recovered. However, at week 7 of treatment for HLH, he developed shock and respiratory failure in the setting of abdominal distention with ascites. Blood and peritoneal cultures yielded Candida lusitaniae; he was treated with amphotericin B and flucytosine. Additionally, he received eight infusions of granulocytes. Seizures persisted and a brain MRI revealed diffuse infra- and supratentorial leptomeningeal enhancement. Examination of CSF showed pleocytosis, but cultures were negative. He was diagnosed with presumptive fungal meningoencephalitis. Seizures were managed with levetiracetam. An enlarged cervical lymph node was also biopsied which revealed multiple granulomas, many of which had central caseating necrosis and degenerating fungal pseudohyphae.\nGiven the lymph node histopathology, a DHR assay was performed and noted to be markedly abnormal (SI 1). Next generation sequencing of genes associated with familial HLH was negative; however, assessment for CGD relevant genes revealed a hemizygous mutation in CYBB (c.1557delA) and confirmed the diagnosis of X-linked CGD. Profound developmental delays related to his severe illness and fungal meningoencephalitis remained. However, with steady developmental progress he ultimately underwent a matched sibling hematopoietic stem cell transplant (HSCT) following conditioning with busulfan, fludarabine, and alemtuzumab. Now at 7 years of age, he is well and requires no immunosuppression. Seizures are controlled on levetiracetam.",
"gender": "Male"
},
{
"age": 17,
"case_id": "PMC7756012_02",
"case_text": "A 17-year-old previously healthy male presented with several days of fever and increased work of breathing, in the setting of 2 weeks of progressive generalized fatigue and episodic changes in mental status. He was empirically treated with ceftriaxone, vancomycin, and acyclovir for presumed sepsis. Initial laboratory evaluation showed pancytopenia and elevated inflammatory markers. Imaging revealed a large consolidation in the right upper lobe and enlarged lymph nodes ( Figure 1D ). Over the next 2 days, his respiratory distress worsened, and he developed hepatosplenomegaly. He was transitioned to doxycycline and ampicillin-sulbactam for treatment of pneumonia. Given lack of clinical improvement despite broad-spectrum antibiotics, a lung biopsy was performed which revealed necrotizing granulomas. Inflammatory markers continued to rise and a diagnosis of HLH was made with the patient meeting the following criteria: persistent fever, splenomegaly, cytopenia, hypertriglyceridemia, elevated ferritin, and elevated soluble IL-2R levels ( Table 1 ); however bone marrow evaluation was normal with no evidence of hemophagocytosis. Because of the patient's clinical findings and recently revealed family history of X-linked CGD in two nephews, a diagnosis of CGD was suspected and amphotericin was added for fungal coverage. CGD was confirmed with abnormal DHR and next generation sequencing of a panel of genes associated with immunodeficiency identifying pathogenic hemizygous variant c.3G>A in CYBB, with no reported variants in primary HLH genes. He was then transitioned to piperacillin-sulbactam and amphotericin, with minocycline for MRSA coverage, followed by initiation of dexamethasone and IVIG, that was met initially with defervescence.\nNineteen days after presentation, he had recurrence of fever and despite treatment with anti-microbials, IVIG, and corticosteroids, he developed profound hypoxemia associated with pulmonary infiltrates and an embolism. Micafungin was added but respiratory failure persisted eventually requiring extracorporeal life support (ECMO) for persistent hypoxemia. On the day of ECMO initiation, his blood culture grew Burkholderia multivoran and trimethoprim-sulfamethoxazole was added for additional therapy. Over the next 10 days, inflammatory markers continued to rise, and blood cultures remained persistently positive. Piperacillin-sulbactam was changed to meropenem, levofloxacin was added, and trimethoprim-sulfamethoxazole continued. Because of persistently rising inflammatory markers and marginal clinical improvement, basiliximab, a monoclonal antibody that antagonizes the IL-2 receptor, was administered with drop in ferritin levels from >100,000 to 70,745 ng/ml after administration. A second dose of basiliximab was administered one day later, and ferritin dropped further to 34,075 ng/ml. However, the patient clinically decompensated on this day and developed pulmonary hemorrhage. Basiliximab was administered a third time 6 days later but ferritin levels subsequently rose to 65,027 ng/ml ( Table 2 ). Because of the patient's critical status and uncontrolled inflammation, emapalumab, a humanized monoclonal antibody that binds and neutralizes interferon-gamma (IFN-gamma), and granulocyte transfusions were administered as life saving measures. Clinical parameters did not improve, and ferritin remained >100,000 ng/ml after emapalumab. Despite these interventions, the patient developed progressive hypotension and died after failed resuscitation from cardiac arrest, 33 days after initial presentation.",
"gender": "Male"
}
] |
PMC7756012
|
[
{
"age": 68,
"case_id": "PMC8799927_01",
"case_text": "A 68-year-old male with past medical history significant of RA (on Methotrexate and Sulfasalazine), polycythaemia, high BMI with performance status of 1, presented with one week history of fever and cough, lymphopenia and raised C-reactive protein (CRP) accompanied by bilateral peripherally-dominant opacities on chest X-ray (Figure 1).\nHe subsequently tested positive for COVID-19 and was admitted to ICU two days later with type 1 respiratory failure. Initially he was treated with Non-invasive ventilation (NIV) but due to further deterioration, he required intubation and ventilation for adequate respiratory support and mild inotropic support. Hence, the intubation was carried out as planned by an expert physician without any immediate complications and he was ventilated on SIMV mode with PEEP of 12, FiO2of 60% on which he was able to maintain his PaO2 of at least 8. Otherwise his cardiovascular and renal function were stable requiring only minimal vasopressor support. There was also acceptable inflammatory response to pre-emptive broad-spectrum antibiotics cover.\nSubsequently, and nearly 2 days later it became apparent that he developed a substantial surgical emphysema over the face, front of upper chest and back, shoulder and upper arms which was progressive. Additionally, oxygen and ventilator requirements were increased needing FiO2 of 100% and PEEP 16 to maintain previously described respiratory parameters. Clinical examination and urgent chest X-ray did not support any deterioration from the COVID-19 previously noted infiltrates neither provided a plausible cause for the surgical emphysema (Figure 2A). Therefore, an urgent CT thorax was carried out which demonstrated significant pneumomediastinum and subcutaneous emphysema with air under diaphragm. There was no suspicion to suggest gastrointestinal tract perforation. Additionally, no pneumothorax was diagnosed and the previously noted COVID-19 infiltrates were stable (Figure 2B).\nIn view of increased respiratory requirements and lack of imaging evidence of any cause for the surgical emphysema and the clinical deterioration, a flexible bronchoscopy was performed, at high suspicion, which exhibited glassy like residue/laceration at 5 o'clock position approximately at 6th tracheal ring measuring 2 cm x 2 cm, possibly from previous clot or laceration. No other signs of penetration through the airways were noted (Figure 3).\nThe most probable cause of his deterioration initially was thought to be secondary to trauma because of his previous intubation but based on its delayed presentation, the fact that the intubation was uneventful and that it was performed by a specialist, a ulcerative lesion related to the active disease process (COVID-19 and/or RA) could not be overlooked, although biopsies were not performed because of the deteriorated condition of the patient and hence no direct evidence of this could be provided. It seems more probable however, that a trauma to the trachea was caused during intubation which was sealed by the endotracheal tube balloon which got moved later on, despite the fact that the patient was not turned to prone position as he has been unwell for this.\nNext, the endotracheal tube position was adjusted (i.e., positioned more peripherally inside the trachea closer to the carina past the laceration under direct vision) and bilateral pectoral fasciotomies were performed with application of two negative suction dressings pumps (Vacuum Assisted Closure - VAC), which helped improve the extent of surgical emphysema. His O2 requirements and ventilation improved importantly and a conservative treatment for his tracheal laceration was decided based on the situation and his clinical condition.\nThe requisite thus far had been a single organ support. However, a few days later, patient's clinical condition deteriorated again by developing atrial fibrillation (AF) and acute kidney and liver injury with hemodynamic compromise. He required increased vasopressor support with moderate doses of noradrenaline, pharmacological cardioversion of AF and hemofiltration was also performed. Despite multi-organ support and accepted management of COVID-19 pneumonitis at the time, his respiratory function deteriorated with increasing oxygen requirements, an increased alveolar to arterial oxygen gradient and worsening of radiological findings of acute respiratory distress syndrome (ARDS) secondary to COVID-19 pneumonitis.\nUnfortunately, the patient did not recover from multi-organ failure and subsequent to multidisciplinary discussion and family involvement, the difficult decision was made to withdraw organ support on the tenth day of critical care admission in the context of worsening multi-organ failure (lung, cardiovascular and renal) caused by COVID-19 infection in a immunosuppressed state.\nAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient's next of kin.",
"gender": "Male"
}
] |
PMC8799927
|
[
{
"age": 56,
"case_id": "PMC6744794_01",
"case_text": "A 56-year-old woman had experienced trigeminal neuralgia (TN) and was treated using GKS. She received 45 Gy at 50% isodose at the proximal cisternal extent of the left trigeminal nerve [Figure 1]. After GKS, she showed no symptoms for 18 years.\nShe experienced a sudden onset of consciousness disturbance and right hemiparesis (National Institutes of Health Stroke Scale score = 20 points). Brain magnetic resonance imaging was performed at the primary hospital. Diffusion-weighted images revealed a hyperintensity in the left insular cortex and a slight hyperintensity in the left MCA territory [Figure 2a]. Magnetic resonance angiography (MRA) revealed occlusion of the horizontal segment of the left MCA [Figure 2b]. She received an intravenous injection of t-PA (Alteplase: 0.6 mg/kg) and was transferred to our hospital. At the time of arrival, no intracranial hemorrhage was noted on brain computed tomography (CT). We subsequently performed digital subtraction angiography (DSA) for only the left internal carotid artery and confirmed the presence of MCA occlusion, even after t-PA injection [Figure 2c]. Mechanical thrombectomy was then performed using the Solitaire FR/2 revascularization device (Medtronic, Minneapolis, MN, USA; onset to reperfusion time: 3 h 13 min), and complete recanalization was achieved [Figure 2d]. Brain CT performed immediately after mechanical thrombectomy revealed subarachnoid hemorrhage (SAH) with a hematoma in the left cerebellar hemisphere [Figure 3a and b]. As CT angiography (CTA) could not confirm the presence of an aneurysm [Figure 3c and d], DSA of the posterior cerebral circulation was performed, and it revealed a small irregular-shaped aneurysm at the branching site of the left circumflex branch of the anterior inferior cerebellar artery [Figure 4a]. Since the aneurysm was located at the radiation field of the previous GKS, it was considered as a GKS-induced aneurysm, and it represented the bleeding source. Thus, we treated it using coil embolization [Figure 4b and c] and performed surgical hematoma removal and decompressive craniectomy. One month after the ischemic attack, she was transferred to a rehabilitation hospital, with a modified Rankin Scale score of 5.\nThe patient's family provided consent for the publication of this case report.",
"gender": "Female"
}
] |
PMC6744794
|
[
{
"age": null,
"case_id": "PMC7970248_01",
"case_text": "An adult spayed female domestic shorthair cat was found crouching down in a yard of a private house. The cat was rescued as it was non-ambulatory in the pelvic limbs and had seemingly been abandoned. The cat was taken to the local veterinary clinic. Therefore, its age and history were unknown except that it had an operation scar on its abdomen. Its body weight was 3.1 kg. Screening tests for feline immunodeficiency virus antibody and feline leukaemia virus antigen were negative. Flea parasites were seen and the haircoat was matted throughout the body. Pain was not obvious when palpating the body. Episodes of head and neck scratching were elicited by palpating the upper cervical region (see Video 1 in the supplementary material), and resembled phantom scratching commonly seen in canine syringomyelia. It was sometimes accompanied by urination. The skin of this region was unremarkable.\nAt the time of the rescue, complete blood count (CBC) and serum chemistry indicated dehydration and inflammation or infection. Under sedation, the haircoat was cut short. The general condition of the cat improved with nutrition support and a flea treatment using a topical formulation of selamectin (Revolution 6%; Zoetis JP). Prior to advanced diagnostic imaging that was conducted 1 month later, CBC and serum chemistry were performed again and the results were unremarkable.\nNeurological examination was performed before advanced diagnostic imaging. Mentation was normal. The cat had non-ambulatory paraparesis in the pelvic limbs without urinary or faecal incontinence (see Video 2 in the supplementary material). Postural reaction of all four limbs was decreased. Spinal reflexes were normal in the thoracic limbs and hyper-reflexia was seen in the pelvic limbs. Nociception was normal in all four limbs. The perineal reflex was intact. Cranial nerve examinations were unremarkable. Neuroanatomical localisation revealed multifocal lesions, including in the C1-C5, C6-T2 and T3-L3 segments of the spinal cord, and/or brain.\nSkeletal survey radiography revealed vertebral exostoses and extensive osteophytes from the upper cervical vertebra to the lower thoracic vertebra (C2-T10) (Figure 1). Changes were more severe at the ventral aspect of the spine, although changes were also found at the dorsal aspect. Morphological asymmetry of the pelvis was also found. No scoliosis or kyphosis was found, but dorsal extension of the neck was observed. Ultrasonography of the abdomen was performed and findings were unremarkable except for the absence of ovaries.\nFurthermore, CT and MRI were performed under general anaesthesia to investigate the causes of the pelvic limb paresis and episodes of head and neck scratching.\nCT of the axial skeleton was conducted using a 16-slice scanner (Supria; Hitachi Medical Systems). CT confirmed vertebral exostoses and extensive osteophytes between C2 and T10 and at the L7-S1 junction with higher CT values (Figure 2a-c), as well as radiographs. A pelvic fracture was also identified (Figure 2d), although this was not considered to be the cause of the pelvic limb paraparesis. CT-based three-dimensional volume rendering (Figure 3) and virtual endoscopy (see Video 3 in the supplementary material) were generated using an imaging workstation (AZE Virtual Place; AZE). CT-based virtual endoscopy revealed stenosis of the vertebral canal of the cervical and the rostral thoracic spine caused by hyperostosis along the spinal canal and protruded calcified intervertebral discs that may have been involved in hyperostosis (see Video 3 in the supplementary material). No ovaries were seen with CT in addition to ultrasonography.\nMRI of the brain and spinal cord was performed with a 0.3-Tesla MRI scanner (AIRIS Vento; Hitachi Medical Systems). Sagittal T2-weighted (T2W) and transverse T2W imaging were obtained for brain MRI. Spinal MRI included the spinal cord between C2 and T11 for the sagittal T2W imaging, and between T2 and T7 for the transverse T2W, T1-weighted (T1W) and subsequent contrast-enhanced T1W imaging. Intravenous administration of a gadolinium-based MRI contrast agent, gadoteridol (0.15 mmol/kg [ProHance; Bracco Diagnostic]), was used for the contrast enhancement.\nBrain MRI showed normal findings. Spinal MRI of the cervicothoracic region revealed a mild dilation of the central canal of the spinal cord with T2 hyperintensity and T1 hypointensity without contrast enhancement at the T4-T5 region (Figure 4). In addition, multiple intervertebral disc protrusions and decreased T2 signal intensities of intervertebral discs were observed in the cervical and thoracic spine.\nBased on the radiographic findings, differential diagnoses included hypervitaminosis A, mucopolysaccharidosis (MPS), diffuse idiopathic skeletal hyperostosis (DISH), osteochondromatosis (also known as multiple cartilaginous exostoses) and infectious spondylitis. However, MPS, DISH, osteochondromatosis and infectious spondylitis were thought to be unlikely for the reasons described in the discussion. Therefore, hypervitaminosis A was considered the most likely diagnosis.\nAfter CT and MRI examination, serum concentrations of vitamin A from the affected cat, as well as two healthy cats used as controls, were measured using high-performance liquid chromatography by a commercial laboratory (Sanritsu Zelkova). The serum vitamin A concentrations of the affected cat and two healthy cats were 1.04, 0.46 and 0.66 micromol/l, respectively, all of which were unremarkable. The reference interval (RI) for serum vitamin A in cats was not available from the laboratory. The serum vitamin A RI in cats is reported to be 1.75-6.77 micromol/l, and plasma vitamin A levels of cats receiving liver diets ranged from 15.74 to 44.71 micromol/l in a study by Seawright et al.\nThe progression of clinical signs such as neurological deficits and pain was not seen in 7 months of follow-up after the rescue, at the time of manuscript submission. Because non-ambulatory paraparesis in the pelvic limbs remained, a wheelchair for cats was put on, which assisted the cat with walking (see Video 2 in the supplementary material).\nFor the treatment of episodes of head and neck scratching that were elicited by palpating the upper cervical region, pregabalin (2.5 mg/kg PO q24h for 1 week and q12h for 1 week [Lyrica; Pfizer]) was used; however, the therapeutic effect was not obvious. Then, oclacitinib (1.3 mg/kg PO q12h [Apoquel; Zoetis JP]) was initiated and clinical improvement was achieved (see Video 1 in the supplementary material). After discontinuing the drug, the sign recurred; thus, it was used as a maintenance treatment for the episodes.",
"gender": "Female"
}
] |
PMC7970248
|
[
{
"age": null,
"case_id": "PMC10416632_01",
"case_text": "Till today, there are six clinical cases (Table 1) that have reported abnormalities resulting from CUL3 mutations, with developmental delay (DD) as the primary phenotype. Nakashima et al. first reported three cases of de novo CUL3 variants resulting in global DD, with or without epilepsy. Two of the patients had infantile spasms, while the other had short stature with mild to severe intellectual disability. Whole-exome sequencing identified one missense variant (c.854 T > C, p.(Val285Ala)) and two frameshift variants (c.137delG, p.(Arg46Leufs*32) and c.1239del, p.(Asp413Glufs*42)). In another case report, Iwafuchi et al. detected a stop-gain mutation in the CUL3 gene from a Japanese patient with ASD. This patient was presented with febrile status epilepticus that led to developmental regression, including the loss of verbal ability, eye contact, and ability to do activities of daily living. Exome sequencing revealed a de novo double base insertion into the CUL3 gene (c.1758_1759insTG, p. (Thr587*)). Furthermore, Kato et al. reported a novel CUL3 gene mutation (c.158G > a, p.Ser53Asn) that resulted in dysmorphic features, such as macrocephaly, characteristic facial features, and stony skin, in a child with global DD. Most recently, Vincent et al. reported the first case of NDD caused by CUL3 splice site variants. The patient presented with congenital hip dysplasia and global DD. Whole-exome sequencing identified splice site variants in CUL3 (c.379-2A > G). These case reports reveal a pattern of global DD and ID associated with CUL3 de novo mutations.",
"gender": "Unknown"
},
{
"age": null,
"case_id": "PMC10416632_02",
"case_text": "Large cohort case-control studies have revealed various de novo mutations in CUL3 are associated with NDDs, including ASD, ID, and DD-like phenotypes.\nNonsense and missense mutations of CUL3 have been identified mainly in ASD patients. Severe de novo nonsense mutations of CUL3 in ASD were found in 2012 when O'Roak et al. performed exome sequencing on 677 ASD individuals from 209 families. Codina-Sola et al. reported CUL3 de novo mutations in a cohort of male idiopathic ASD patients (n = 36). Larger cohorts were carried out thereafter. De Rubeis et al. analyzed rare coding variants in 3,871 ASD cases and 9,937 ancestry-matched or parental controls, which identified CUL3 as one of 107 high-risk ASD genes that cause de novo loss of function (LoF) mutations in more than 5% of ASD. Sanders et al. reported CUL3 de novo CNVs in patients with ASD (10,220 patients from 2,591 families) in the Simons Simplex Collection (SSC) data. The largest array of SPARK analysis findings to date (including 42,607 autism cases) identified CUL3 as a genetic high-confidence LoF variant. The latest release of whole-genome sequencing (WGS) data from the Autism Speaks MSSNG resource1 identified CUL3 as one of the 134 ASD-associated genes, with a false discovery rate (FDR) of <0.1, in 5,100 ASD and 6,212 non-ASD parents and siblings. In the Chinese ASD cohort, Wang et al. conducted a study of recurrent de novo and likely gene-disruptive (LGD) mutations (n = 1,543), which identified CUL3 de novo LGD recurrences.\nMissense mutations in CUL3 have also been identified in cohorts of ASD combine with ID, DD, or NDDs. Hormozdiari et al. analyzed exome sequencing data from 1,116 individuals with ASD and ID, which identified patients with severe Cul3 missense mutations have more significant intellectual impairment. Wang et al. performed an integrated gene analysis of de novo variants in 15,560 ASD and 31,052 DD, identifying CUL3 as one of the de novo variance-rich genes in 138 NDDs combinations. In a targeted sequencing study of 208 candidate genes in 11,730 patients and 2,867 controls, CUL3 was found to reach de novo significance and identified as one of the 91 NDDs risk genes with ASD and DD biases. da Silva Montenegro et al. performed a meta-analysis with more than 20,000 patients from NDDs cohorts and found mutations in CUL3.\nOverall, the above evidence supports the notion that CUL3 is a high-risk gene for NDDs, especially ASD.",
"gender": "Male"
}
] |
PMC10416632
|
[
{
"age": 66,
"case_id": "PMC5648305_01",
"case_text": "Written consent was obtained from the patient for the publication of his case and images. A 66-year-old Indian male patient presented to the Tuberculosis Control Unit after sudden onset of near syncope, nausea, diaphoresis, light-headedness, and a wide-staring gaze with upward and lateral deviation of eyes 30 minutes after consuming newly-prescribed RHEZ. These symptoms resolved on the administration of diphenhydramine 25 mg intravenously at the Emergency Department. The patient was referred, initially, to the Department of Rheumatology, Allergy and Immunology based on the suspicion of a reaction to RHEZ. A diagnosis of anaphylaxis-like and possibly idiosyncratic reaction to rifampicin was made.\nOn further questioning by the primary team, the patient reported that while he was aware of his surroundings and was able to hear conversations around him, he felt \"physical blocked\" in that he was unable to respond with purposeful voluntary movements or speech; he additionally described abdominal discomfort and generalized weakness.\nThe patient had just been prescribed daily rifampicin 600 mg, isoniazid 300 mg, ethambutol 1.6 g, pyrazinamide 1.75 g (i.e., standard RHEZ combination therapy for TB of uncertain origin and resistance, according to his weight of 98.3 kg) and pyridoxine 10 mg after increased nodular opacities in the left upper zone were observed on sequential chest X-rays (Figures 1 and 2), suggestive of granulomata. A small calcified pleural plaque was also noted. Blood cultures, sputum cultures, and Mycobacterium tuberculosis polymerase chain reaction were negative.\nOn his initial presentation after the near syncope, the patient's vitals were stable and physical examination, including neurological examination, did not reveal any conclusive findings. A full blood count, liver function test, thyroid function test, drug screen, troponin I, electrocardiogram (Figure 3), and a two-dimensional echocardiography were performed.\nHowever, the diagnosis was subsequently changed to OGC based on the more complete history recorded. Another possible cause of OGC would include trauma. However, the patient did not suffer from any trauma recently.",
"gender": "Male"
}
] |
PMC5648305
|
[
{
"age": 48,
"case_id": "PMC8733335_01",
"case_text": "Our patient is a 48-year-old male with intrahepatic cholangiocarcinoma (ICC) with a history of psoriasis for more than 20 years. After receiving multi-line treatment, including surgery, chemotherapy, and radiotherapy, among others, the effect was not good and the patient's disease progressed. According to the results of clinical trials on biliary tumors, PD-1 antibody combined with lenvatinib was tried. There was no obvious abnormality in urine routine during baseline examination; meanwhile, the patient's psoriasis was also in an inactive period, which has been stable for a long time and did not require drug control. However, after combination treatment with lenvatinib and nivolumab, psoriasis recurred, with scattered rashes all over the body, and skin toxicity symptoms aggravated with the increase of the cumulative dose of the PD-1 antibody. The patient developed urinary tract irritation after three cycles. Urine examination revealed 375/mul white blood cells (WBCs) in the urine ( Figure 1 ). Although no bacteria were found in the urine culture, the possibility of bacterial cystitis was still considered after consultation with the urology department based on the patient's symptoms at that time. After antibiotic treatment, laboratory tests had indeed improved, but the patient's symptoms did not get better. Therefore, the treatment was discontinued. However, the patient's tumor indicators increased due to the discontinuation of lenvatinib and PD-1 antibody ( Figure 1 ). Imaging examinations also revealed new lesions located on the right posterior lobe of the liver and above the duodenum on the right side of the pancreatic head in the abdominal cavity ( Figure 2 ). In general surgery consultation, this patient was considered to have a chance of surgery, so an operation was performed. One month after the second operation, the patient's tumor indicators decreased and then increased again ( Figure 1 ). Except for a slight thickening of the local omentum, no lesions were found on imaging. At the same time, the patient's urinary tract symptoms improved after the drug has been withdrawn for more than 3 months. Therefore, Gemox chemotherapy (gemcitabine+oxaliplatin) was considered after the operation. Meanwhile, the patient's immunohistochemistry was positive for PD-L1. Taking the improvement of curative effect into account, and with the patient's insistence on trying, the treatment plan was finally determined as Gemox combined with the PD-L1 antibody. The patient then did not develop skin toxicity. After three cycles, the tumor markers dropped significantly, but bladder irritation reoccurred, which was significantly worse than before. Urine examination revealed that WBCs were 2,818/mul ( Figure 1 ) and bacteria were 512/mul. After consultation with the Department of Urology and Nephrology, bilateral ureteral stent implantation and cystoscopy and biopsy were decided. The result of the bladder biopsy indicated chronic inflammation of mucosal tissue, mucosal erosion in some areas, and proliferation of granulation tissues and fibroblasts ( Figure 3 ). After the multidisciplinary consultation, immune-related cystitis was considered; treatment with steroid hormones was given, which started at 2 mg/kg, then slowly decreased. The urinary tract irritation symptoms were relieved, and the laboratory examination was also significantly improved. After 4 weeks, the urine routine was reviewed, and the WBC count was 66/mul. At present, during the hormone reduction period, urine routine and carbohydrate antigen 19-9 (CA19-9) are continued to be monitored, and imaging examinations are performed regularly (including MRI and PET-CT). In the follow-up treatment, it was considered that this patient cannot tolerate the side effects of immunotherapy. Whether hormones affect the efficacy of immunotherapy is currently controversial, so chemotherapy only was considered.",
"gender": "Male"
}
] |
PMC8733335
|
[
{
"age": 19,
"case_id": "PMC4891586_01",
"case_text": "A 19-year-old female fell 20 feet from a roof and presented with a complete laceration of the lower lip and bilateral otorrhagia. A maxillofacial computed tomography (CT) exam (Fig. 1) revealed a nondisplaced fracture at the mandibular symphysis and bilateral temporomandibular joint (TMJ) fractures. The right TMJ fracture was at the condylar neck. The left TMJ fracture was within the intracapsular portion of the condyle. There was lateral displacement of the left TMJ. There were comminuted fractures of the anterior walls of both external auditory canals (EAC) with acute blood in the canals (Fig. 2). The EAC fracture fragments were more inferiorly and posteriorly displaced on the left (Fig. 3).",
"gender": "Female"
}
] |
PMC4891586
|
[
{
"age": 55,
"case_id": "PMC10408600_01",
"case_text": "A 55-year-old female with no significant medical history was initially evaluated because of the right-sided radiculopathy in a C6 distribution. She complained of constant mild neck pain. Her symptoms had been persistent for approximately 9 months. She had no neurological deficits on physical examination and had no signs of myelopathy. Before evaluation, she had tried physical therapy, acupuncture, oral steroids, chiropractic care, gabapentin, and topical analgesics without relief. In addition, she underwent C7-T1 interlaminar injection of steroids with no change in symptoms.\nInitial noncontrast computed tomography (CT) image demonstrated a bony destructive process involving the right C5 pedicle and superior facet, concerning for an aggressive neoplastic process. Follow-up contrast-enhanced magnetic resonance imaging (MRI) demonstrated extradural enhancement along the right side at C4-C6, within the right C5-C6 neuroforamen partially insinuating into the bone. Several MRI sequences also demonstrated flow related artifact within the area of extradural enhancement [Figures 1a and b].\nAt this time, she had been evaluated by an orthopedic surgeon who initially planned C4-C7 anterior cervical discectomy and fusion. However, because the MRI suggested vascular lesion, neurovascular consultation and further imaging studies were instead pursued. CT angiography (CTA) was then obtained demonstrating multilevel asymmetric venous epidural enhancement spanning C4-C6 with a focal extradural venous pouch at the C5-C6 level [Figures 1c and d]. This further supported the presence of a vascular lesion, specifically an extradural AVF. Because of this, she then underwent outpatient angiography followed by embolization of the cervical foraminal AVF.\nThe digital subtraction angiography (DSA) revealed an AVF supplied from the deep cervical branch of the costocervical trunk. There was a smaller contributor from the inferior thyroid branch of the thyrocervical trunk [Figure 2a].\nOne week after DSA, she underwent embolization of the fistula. A transradial approach was used with a Bernstein select catheter and a 256 cm 027 Headway microcatheter. The microcatheter was wedged in the distal most part of the deep cervical branch. A single coil was deployed at the neck of the venous varix (distal to the fistula) to prevent filling densely packing the varix with embolic material and preserving its mass effect. Onyx 18 was then infused upstream of the coil and allowed to disperse throughout the fistulous network in the typical fashion of \"lava flow.\" At the conclusion of the embolization, the fistula appears completely obliterated [Figure 2b].\nPostoperatively, she was started on a short decadron taper over 5-day course. She was discharged to home the following day having met all expected postoperative milestones. At 1-week postoperatively, she had no change in her radicular pain and remained full strength. She continued to take gabapentin for pain relief but was weaning off. An MRI and CTA were repeated at 6-week postoperatively which demonstrated complete obliteration of the C6 AVF [Figures 3a and b]. Her symptoms at this time entirely resolved and she was off of all her preoperative analgesics and muscle relaxants.",
"gender": "Female"
}
] |
PMC10408600
|
[
{
"age": 0,
"case_id": "PMC9123637_01",
"case_text": "An 87-day-old female infant presented to the hospital with increasingly frequent non-bilious vomiting and regurgitation in addition to failure to gain weight and weight loss according to her mother. She was a well-baby with no diseases or anomalies and weighed 2.7 kg at birth. During the last 20 days prior to admission, she experienced frequent and increasing regurgitation and vomiting, causing the loss of 400 grams more of her weight. At the time of admission, the patient weighed 4.5 kg with a Z-score of -2 (weight for length). She was afebrile with stable vital signs for her age, including a pulse rate of 120 beats/min, a respiratory rate of 23 breaths/min, and blood pressure of 90/60 (mm Hg). Initial physical examination revealed nothing but failure to thrive. She was neither ill, nor toxic, nor cyanotic. Her heart sounds were normal and rhythmic without any murmurs. Respiratory sounds were clear. The abdomen was soft with active bowel sounds. The rest of her physical examination and electrocardiogram (ECG) were also normal. All laboratory findings including complete blood count, urine, and stool exams were normal. The abdominal ultrasound revealed stomach contents passing through a non-hypertrophied pylorus that was seen to open and close normally. A small amount of free fluids was detected in the Morrison space with a spleen size of 61 mm on midclavicular line. Pelvic and prominent mesenteric lymph nodes were estimated to be up to 4 mm. The infant's upper gastrointestinal (GI) series showed nasopharyngeal regurgitation and compression effect on posterior aspect of esophagus at the level of aorta arc, which was suggestive of double aortic arch or, less probably, aberrant right subclavian artery (Figure 1). A barium meal study revealed severe gastroesophageal reflux, and her small bowel follow through revealed a nodular filling defect in the ileac loops, suggestive of nodular lymphoid hyperplasia. Echocardiogram, which was highly recommended due to her barium study results, showed a right-sided aortic arch with a small atrial septal defect (ASD). Cardiac function and pulmonary artery pressure (PAP) were reported to be normal. \nThe patient underwent a multi-slice spiral computerized tomography (CT) angiography of the heart and vasculature using a non-ionic contrast and a saline chaser via dual injector through the intravenous route. Multiple axial and sagittal images with multi-planar reformation (MPR), maximum intensity projection (MIP), and volume rendering technique (VRT) reconstruction showed a SDS levo-cardiac heart with atrioventricular and ventriculoarterial concordance and intact ventricular septum (IVS) with no sign of permeant ductus arteriosus (PDA). It also revealed a right-sided aortic arch with an aberrant left subclavian artery with notable compression on the esophagus. The main pulmonary artery and its branches were prominent due to a left-to-right shunt. All pulmonary veins returned to the left atrium with no sign of left superior vena cava (LSVC) (Figure 2).",
"gender": "Female"
}
] |
PMC9123637
|
[
{
"age": 69,
"case_id": "PMC3700967_01",
"case_text": "A 69-year-old woman presented to our hospital with a 2-week history of nausea, abdominal pain, extreme generalized weakness and fatigue, and a 1-week history of poor oral intake. Additionally, she had noticed a new onset of pruritic rash over the abdomen, spreading over the trunk. Two weeks prior to the onset of her symptoms, she had presented with dysuria to her primary care physician and was treated with a week's course of ciprofloxacin for presumed urinary tract infection, but, despite this, her symptoms persisted.\nHer past medical history was significant for atrial fibrillation, lumpectomy for breast cancer, done six years previously, and diverticulosis.\nOn examination at our institution, her temperature was 37.2 C, her blood pressure was 110/70 mmHg, and her pulse rate was 156 beats per minute. Positive physical examination findings were a diffuse, predominantly truncal, maculopapular, erythematous rash. This was nonpalpable and nonblanching. Cardiovascular exam was positive for rapid atrial fibrillation. Examination of her lower extremities revealed severe tenderness over both calf areas but no pedal edema. A separate petechial rash was noted over the shins. Abdominal examination revealed no masses, but she demonstrated generalized tenderness on palpation.\nLaboratory data revealed hemoglobin (Hb) 9.7 g/dL, hematocrit 32.2%, leukocyte count of 9300 cells/UL (differential: granulocytes 91%, lymphocytes 2%, monocytes 6%, and eosinophils 1%), platelets of 276,000/mm3, blood urea nitrogen (BUN) of 134 mg/dL (normal, 10-20 mg/dL), creatinine, 11.6 mg/dL (her baseline creatinine a month prior to her presentation was 1.1 mg/dL). In addition, her sodium was 125 mmol/L (normal, 135-146 mmol/L); chloride, 88 mmol/L (normal, 96-106 mmol/L); potassium, 4.2 mmol/L (normal, 3.5-5.1 mmol/L); phosphorus, 7.5 mg/dL (normal, 2.7-4.5 mg/dL); and bicarbonate, 18 mmol/L (normal, 24-32 mmol/L). Urine analysis showed specific gravity of 1.010; trace proteins, 3 to 5 dysmorphic red blood cells; no casts and no leucocytes; and glucose, 50 mg/dL. The 24-hour urine microalbumin/creatinine ratio was 797 mcg/mg with a urine creatinine of 30.6 mg/dL. Although there was no peripheral eosinophillia, her urine was positive for eosinophils by Wright's stain. Liver function tests were normal.\nSerum protein electrophoresis was normal, while her antinuclear antibody and serologies for hepatitis B and C were all negative. Her Complement component3 (C3) was normal at 112 and Complement component 4 (C4) was mildly depressed at 15.1.\nEnzyme-linked immunosorbent assay (ELISA) was used to test for presence of serum myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA); this was found elevated to 54 EU, (normal value is <20 EU). Her P-Anti-neutrophil cytoplasmic antibody titer was 1:40.\nHuman immunodeficiency virus was negative, so was the Antinuclear antibody (ANA). C-Reactive Protein (CRP) was 22.9 mg/dL and Erythrocyte sedimentation rate (ESR) was >140 mm/hr, the results of tests that were done after the biopsy diagnosis was made.\nA renal biopsy was performed after admission, and it showed acute necrotizing intrarenal vasculitis with diffuse acute ischemic tubular injury. Low magnification showed an interlobular or arcuate artery showing full-thickness fibrinoid necrosis with luminal occlusion. One glomerulus out of 25 in the specimen showed a fibrocellular crescent and global glomerulosclerosis. The other glomeruli were unaffected. Additionally, there was no evidence of acute interstitial nephritis on the biopsy specimen.\nAn magnetic resonance image of the brain at that time revealed nonspecific white matter signal changes, likely representing small vessel ischemic disease but vasculitis could not be definitively ruled out. Renal arteriogram was negative for micro aneurysms.\nGiven her severe uremia, she was placed on intermittent hemodialysis via a split-tip tunneled hemodialysis catheter. In addition, she was started on a daily oral cyclophosphamide at a dose of 1 mg/kg/day and daily oral prednisone at a dose of 1 mg/kg/day initially. Six weeks into her treatment, her creatinine fell to 1.9 mg/dL and intermittent hemodialysis was discontinued (Table 1).",
"gender": "Female"
}
] |
PMC3700967
|
[
{
"age": 9,
"case_id": "PMC6347510_01",
"case_text": "Here we describe a 9-year-old girl with microcephaly and mild cerebellar hypoplasia with severe intellectual and motor disability (Fig. 1A,B). She was born full term after an uneventful pregnancy. Parents noticed delay in achieving milestones. She rolled over at 6 months, sat at 12 months and walked at 5 years. She is a happy and social child with global developmental delay. She is ataxic, with motor incoordination in both upper and lower extremities which is more pronounced on left side. She has good core stabilization of the trunk with spinal exaggeration in extensor muscles, suggesting some truncal weakness. She exhibits atypical gait pattern and foot drop during walking and running. In addition, she internally rotates her left lower extremity likely due to decreased tone associated with left hip extensors. From a motor function perspective, she appears to be delayed in both gross and fine motor skills, with greater delays in fine motor abilities. Although she exhibits a clear desire to communicate, there is no verbal communication; only occasionally does she respond with appropriate syllable production. She responds to simple commands and demonstrates some self-stimulation behaviors.\nIn addition to the psychomotor and intellectual delays described above, the subject also has bilateral epicanthus and bilateral retinal dystrophy. The patient was first seen at the institution for an eye examination at 5 years of age. She had a history of myopia and an oculodigital reflex but no nyctalopia or photosensitivity. Paternal family history was positive for myopia and retinal detachment. Examination showed no paradoxical pupillary constriction in the dark or visual field constriction to confrontation and the optic nerves were pink with a scleral crescent, but the retinal arterioles were attenuated. However, the optic nerve looked normally developed at this stage (Fig. 1C). The girl also had ptosis and epicanthus. In view of the oculodigital reflex and arteriolar attenuation, an ERG was performed that showed severe loss of rod greater than cone photoreceptors, indicating a retinal dystrophy (Fig. 1D-E). She developed photosensitivity and difficulty adapting indoors after being outside. The optic nerves showed evidence of mild to moderate atrophy two years later, but the ERG remained relatively stable. At no time did she have nystagmus or strabismus. Examination remained relatively stable at age 9 years except for an increase in her myopia. She was unable to perform optotype acuity testing. Upon exome sequencing a single mutation in the CASK gene is observed (NM_003688.3(CASK):c.626T>C (p.Leu209Pro); Variation ID: 432816). The variant was not observed in either parent, indicating that the mutation was de novo.\nThis mutation has been previously reported as a loss-of-function mutation, although the mechanism underlying the pathogenicity is not clear. The substituted leucine in CASK's CaMK domain (Fig. 2A) at position 209 is highly conserved in all species surveyed (Fig. 2B), indicating that it may be a critical part of CASK's primary structure. The leucine is situated in the alphaF helix of the C-terminus lobe of the CaM-kinase domain (Fig. 2D). None of the CaM-kinases in the human kinome contain a cyclic amino acid at this site. A change in the side chain at this position is thus likely to alter intra-molecular interactions and produce secondary and tertiary structural defects. Molecular dynamics (MD) simulations were done to computationally model the movement of CASK at the atomic level over a period of time at room temperature in an aqueous environment; MD simulations can provide insight into the impact of a mutation on a protein's structure, if an atomic model of the wildtype structure is available. When MD simulations were done on the isolated CaM-kinase structure (a previously solved crystal structure, an analysis of the simulations indicates that the addition of a proline at this position does not destabilize the overall structure of the isolated domain, as indicated by the nearly identical average radii of gyration (19.37398A+- 0.20033 and 19.5173A +- 0.254 for wildtype and CASKL209P, respectively) and root mean square deviation of the backbone relative to the starting structure (1.57455A +-0.31 and 1.52034A +- 0.29 for wildtype and CASKL209P, respectively) over the course of the 100 ns MD trajectories for CASKL209P structure as compared to the wildtype structure (Fig. 2C). MD simulations, by their very nature, yield millions of individual protein conformations, but most of these conformations differ from each other very little. A cluster analysis allows investigators to identify and then examine the most common structure(s) populated during an MD simulation. When the two structures representing the most populated cluster are superimposed using the MatchMaker tool in Chimera, the root mean square deviation between the two structures is 1.252A; for comparison, structures of identical proteins within the Protein Databank can exhibit RMSDs up to 1.2 A, due to variability arising from inherent protein flexibility as well as the resolution limits of the methods used to determine protein structure. From the MD trajectories, calculations of the root mean square fluctuation (RMSF) of the alpha-carbons for both wildtype and CASKL209P were done to, in turn, calculate B-factors at each amino acid position within the CAMK domain. B-factors provide a measure of mobility at a given site, and a comparison between B-factor values by sequence position revealed very few dramatic differences throughout the domain due to the L209P mutation, with the exception of increased mobility in two specific regions (Fig. 2D,E), both located in the activation loop of the CAMK domain: residues 166-168 and 174-176. Both the alphaF helix, where the L209P mutation is located, and the activation loop, which is predicted by the MD simulations to be impacted by the L209P mutation, are considered critical structural components of the core kinase domain, but these changes do not point, in isolation, to a global unfolding of CASK's CAMK domain due to the L209P residue. These simulations are done on an isolated domain of CASK, however, making it impossible to rule out the possibility of disruption of native inter-domain contacts.\nWe have previously published a simple assay to test structurally unstable CASK mutations. This involves transient over-expression of a GFP-CASK fusion protein using a strong cytomegalovirus promoter (CMV) in human embryonic kidney (HEK 293) cells. Typically GFP-CASK can be visualized using a confocal microscope and is evenly distributed throughout the cytoplasm but excluded from the nucleus (Figure 3A). Misfolding of CASK leads to formation of visible \"cotton-wool\"-like aggregates in the cytoplasm. Upon overexpression of CASKL209P, aggregates are readily observable, indicating that the protein has a tendency to misfold and aggregate (Figure 3B). In cells where large aggregates are not observed (67%) (Figure 3C), we observe a small punctate distribution not previously seen with the other mutations that we have tested. CASKL209P thus may also be producing much smaller aggregates, thereby resulting in an underestimate of the amount of protein aggregation caused by this mutation. We therefore tested the solubility of CASKL209P by transfecting HEK293 cells with GFP, GFP-CASK and GFP-CASKL209P and solubilizing after 2 days in culture using a solubilizing buffer. Both endogenous CASK and GFP-CASK exhibited a high degree of solubility with little protein left in pellet (Figure 3D). CASKL209P, however, was less soluble, with large amounts remaining in pellet. Thus our data indicate that the L209P mutation results in a propensity for CASK to misfold in a disordered manner, reducing the amount of soluble and possibly functional protein present in the cell.\nTo determine if the small amount of solubilizable CASKL209P retained any functionality, we examined the biochemical competence of CASKL209P. In previous work, we demonstrated that CASK mutations associated with microcephaly disrupt the interaction between CASK and neurexin. We therefore first tested the interaction between CASKL209P and neurexin in a cellular milieu using a previously described recruitment assay. The assay relies on the ability of membrane-bound neurexin to recruit the cytosolic protein CASK. The recruitment can be easily observed using a confocal microscope in a large, flat cell (with a high cytosolic-to-nuclear ratio) such as HEK293 cells (Figure 4B). Although CASKL209P aggregates in many cells, neurexin is still able to recruit some CASKL209P, indicating that soluble CASKL209P retains its capacity to interact with neurexin (Figure 4D). This finding was confirmed using a GST pull-down experiment (Figure 5A). The cytosolic tail of rat neurexin-1 fused with GST was expressed, purified, and immobilized on glutathione beads. GST-neurexin cytosolic tail (GST-Nx-CT) beads were used to precipitate CASK (both wild-type and CASKL209P) that was expressed in HEK 293 cells. The results from the pull-down experiment confirm that the soluble population of CASKL209P retains its ability to interact with neurexin.\nCASK is a scaffolding protein involved in an evolutionarily conserved ternary complex with Mint1 and Veli. Veli interacts with CASK via its L27 domain whereas Mint1 interacts with CASK via its CaMK domain. To determine whether CASKL209P is capable of forming this ternary complex, GFP-CASK was expressed in HEK293 cells, and the lysate from these cells was combined with rat brain lysate to allow the exogenous CASK to form complexes with brain-derived proteins (Figure 5B). GFP-CASK was then immunoprecipitated with GFP antibodies, and immunoprecipitates were blotted for Veli and Mint1 (Figure 5D), revealing that CASKL209P can still bind to Veli, but its interaction with Mint1 is disrupted. The L209P mutation in CASK is thus likely to disrupt its regulatory scaffolding function that links neurexin to molecules like Mint1.",
"gender": "Female"
}
] |
PMC6347510
|
[
{
"age": 60,
"case_id": "PMC5998277_01",
"case_text": "A 60-year-old male with nonalcoholic steatohepatitis-induced cirrhosis complicated by portal hypertension and esophageal varices presented to the hospital for shortness of breath and respiratory distress. He had multiple prior hospitalizations and was undergoing evaluation for liver transplant. His MELD score was 19 on admission. There was a concern for pneumonia on presentation and he was started on empiric reatment with broad-spectrum antibiotics. On hospital day four, he experienced worsening respiratory distress and developed hypoxic respiratory failure. This occurred despite optimal use of diuresis, noninvasive ventilation and paracenteses. He was intubated on hospital day five. On the day of intubation, his total bilirubin was 2.1, serum creatinine 1.65, international normalized ratio (INR) 2.4 and serum sodium of 142 (MELD of 16). Mechanical ventilation was with assist control with tidal volumes of 350 mL, rate of 32, PEEP of 16 on 90% FiO2. Arterial blood gas showed a pH of 7.25, CO2 of 55, and O2 of 116.\nAfter intubation, he had progressive and refractory hypoxemia requiring increasing PEEP with high FiO2 to maintain oxygenation. Four days after intubation, he was found to have large apical bilateral pneumothoraces that required emergent bilateral chest tube placement. The development of bilateral pneumothoraces was in part due to increasing PEEP to meet the oxygenation demands. He had progressive coagulopathy during his ICU course as his INR was 4.2 and PT 46.8. It was felt that urgent correction of coagulopathy was required prior to the procedure, and that it should be done without excessive volume administered. Therefore, he was given 2.9 million units of 4-factor prothrombin complex concentrate (4F-PCC) (based on weight) and within 1 h following administration his INR was measured at 1.5. Subsequently, bilateral chest tubes were placed. There was an immediate improvement of oxygenation, and there were no bleeding complications. One day after the placement of the bilateral chest tubes the patient died from ongoing hepatic decompensation.",
"gender": "Male"
}
] |
PMC5998277
|
[
{
"age": 33,
"case_id": "PMC6586124_01",
"case_text": "A 33-year-old Caucasian female, Gravida 2 Para 2, presented to the emergency department with sudden onset of moderate sharp left-sided pleuritic chest pain and SOB for one day. She had a past medical history of factor V Leiden (diagnosed at age 16) and a family history of factor V Leiden and deep venous thrombosis (DVT) in her mother. She denied any previous VTE, recent surgery, prolonged immobilization, anticoagulant use, smoking or cancer. On further questioning, she admitted having a progestin intrauterine device placed nine months ago.\nReview of systems was positive only for the chief complaints. Physical exam showed shallow breathing due to pain on deep inspiration. Heart rate was 88 beats/minute and temperature 98.8 F; lung exam revealed bilateral normal vesicular breath sounds with no wheezes or crepitation; no leg edema, or calf tenderness. The rest of the physical exam was unremarkable.\nFirst sets of labs including, complete blood count (CBC), complete metabolic panel (CMP), troponin, arterial blood gas (ABG) and urine toxicology were within normal limits.\nElectrocardiogram (EKG) (Figure 1) showed sinus rhythm with a rate of 78, T wave inversion in Lead 3 and V3. Echocardiogram showed normal ejection fraction (55-60%) with no right ventricular strain pattern. Her D-dimer level was elevated,1440 ng/ml, (normal limits 0-500 ng/ml). Lower extremity venous Doppler showed no evidence of deep venous thrombosis.\nDue to the high suspicion of PE, computerized tomography pulmonary angiography (CTPA) (Figures 2 and 3) was done which revealed bilateral subsegmental pulmonary embolism. It also showed mild subsegmental pulmonary infarctions of the lower lobes. She was started on subcutaneous enoxaparin and later transitioned to apixaban (Eliquis). During her hospital stay, she was hemodynamically stable. Her chest pain persisted for a couple of days and ultimately resolved with analgesia. She was discharged on the 3rd day, to follow up as outpatient.\nShe was counseled about avoidance of risk factors and to follow up with hematology and gynecology clinic for removal of her IUD on discharge.",
"gender": "Female"
}
] |
PMC6586124
|
[
{
"age": 39,
"case_id": "PMC5899866_01",
"case_text": "A 39-year-old otherwise healthy male with newly diagnosed mixed-lineage acute monocytic and B-cell lymphoblastic leukemia was transferred to our institution for initiation of chemotherapy. Prior to transfer, he had received intrathecal methotrexate and oral dexamethasone, as well as vancomycin and cefepime for neutropenic fever and positive blood cultures growing gram-positive cocci. At our institution, the patient was started on GRAALL (Group for Research on Adult Acute Lymphoblastic Leukemia) 2003 chemotherapy. He received cefepime and vancomycin for persistent neutropenic fevers. Eventually, cefepime was switched to meropenem due to development of multifocal pneumonia during his hospital course. Shortly thereafter, liposomal amphotericin was initiated for presumed invasive pulmonary aspergillosis after a bronchoalveolar lavage (BAL) from a diagnostic bronchoscopy revealed a positive galactomannan antigen; however no organisms were seen on gram stain or identified on culture. He was treated with vancomycin for 8 days and meropenem for 17 days, after which he defervesced. Nevertheless, fevers recurred on hospital day 20 and shortly after; blood cultures returned with gram-negative rods at which point vancomycin and cefepime were reinitiated.\nThree days later (hospital day 23), the patient reported pain and developed swelling and erythema of his left forearm. On physical examination, the left forearm was swollen, tense, and erythematous, but there were no areas of fluctuance, subcutaneous crepitance, or bullae noted. Duplex ultrasound of the upper extremities showed no evidence of deep vein thrombosis. However, given the acute onset of pain and swelling, orthopedic surgery was consulted for possible necrotizing infection and compartment syndrome. Laboratory testing disclosed a c-reactive protein (CRP) of 12.90 mg/dL, a white blood cell count of less than 0.1 x 109/L, a sodium of 142 mmol/L, a glucose of 110 mg/dL, a hemoglobin of 7.2 g/dL, and a creatinine of 0.96 mg/dL, yielding a LRINEC score of 2. It was felt, partly due to this low score, that the patient had a severe cellulitis without necrotizing infection or compartment syndrome. Moreover, based on the patient's clinical picture and the available data at the time, invasive testing for compartment syndrome was deemed unnecessary by the orthopedics service. No additional imaging was ordered at this point. Within 10 hours, the swelling and pain had progressed to his entire left upper extremity (Figure 1) and the patient developed hypotension. He was then transferred to the intensive care unit for refractory septic shock and severe metabolic derangement. At this time, laboratory studies were notable for a CRP of 18.80 mg/dL, a white blood cell count of 0.2 x 109/L, a sodium of 142 mmol/L, a glucose of 116 mg/dL, a hemoglobin of 5.9 g/dL, and a creatinine of 1.06 mg/dL yielding a LRINEC score of 6. The patient continued to clinically decline rapidly despite broadening of his antibiotic regimen (vancomycin, meropenem, gentamicin, and amphotericin B) and was taken to the operating room by the orthopedic surgery service due to concern of a rapidly progressing NSTI.\nIn the operating room, the entire left upper extremity was prepped, and an initial incision was made over the dorsum of the hand. Exploration of the surrounding tissue revealed necrotic fat, hemorrhagic changes, and gross edema. The expressed fluid was tan but did not have the classic \"dishwater\" appearance of necrotizing fasciitis, nor was it malodorous. The fascia was thickened and opaque. A counterincision was then made proximally over the biceps muscle in the proximal brachium (Figure 2). This region displayed the same tan drainage with associated fat necrosis, and thrombosed vessels were also appreciated in the subcutaneous tissue. Regions of the thickened, diseased-appearing fascia were excised, revealing that the underlying musculature appeared necrotic, noncontractile, and nonviable.\nAt this point during the procedure, the anesthesiologist noted that multiple vasopressors were being used to maintain the patient's blood pressure, and there was concern that he was clinically deteriorating. Given the extensive involvement of, essentially, the entire limb and the concern that the bacterial load could not be adequately controlled in this hemodynamically unstable patient, the decision was made to proceed with an emergent glenohumeral amputation. The deltoid muscle remained healthy-appearing and contractile, and thus a lateral-based flap composed of the deltoid and overlying skin and soft tissue was planned. Once the amputation was performed, the wound was copiously irrigated using several liters of normal saline to minimize the remaining bacterial load. Hemostasis was subsequently achieved, a drain was placed, and the flap closure was completed. The patient's hemodynamic status improved during closure, and he was transferred back to the intensive care unit for continued care.\nThe previously drawn blood culture returned on postoperative day (POD) 0, growing Stenotrophomonas maltophilia in both aerobic and anaerobic cultures, at which point trimethoprim-sulfamethoxazole was initiated. Pathology of the surgical specimen confirmed the diagnosis of a NSTI, and multiple tissue cultures grew only S. maltophilia. Despite appropriate antibiotic therapy and surgical intervention, the patient remained persistently bacteremic and in refractory shock despite aggressive medical therapy. On POD1, new necrotic skin areas were noted at the surgical site, and cardiothoracic surgery was consulted to evaluate further surgical intervention. The team decided against this, given the patient's very poor prognosis. After discussion with the family, the patient was transitioned to comfort care and passed away shortly thereafter.",
"gender": "Male"
}
] |
PMC5899866
|
[
{
"age": 66,
"case_id": "PMC6180851_01",
"case_text": "A 66-year-old female with a history of endometrioid endometrial carcinoma was sent to our institution with abdominal and pelvic pain. The physical examination and laboratory results were unremarkable. The creatinine level was 0.81 mg dl-1. A contrast-enhanced abdominal and pelvic CT scan was performed that revealed a mass with a fatty density within the right upper kidney and a tumour thrombus that extended through the right renal vein up to the point of confluence with the inferior vena cava (IVC).\nrenal angiomyolipoma (AML)\nperirenal liposarcoma\nrenal cell carcinoma (RCC)\nrenal oncocytoma.",
"gender": "Female"
}
] |
PMC6180851
|
[
{
"age": 62,
"case_id": "PMC5771915_01",
"case_text": "A 62-year-old woman was referred to the emergency department in our hospital due to a body height fall. She was presented with severe pain in her left hip and the inability to walk. Her following examination revealed a 30-year-old femoral neck fracture. The option of treatment at that time was an arthrodesis of the left hip. Having presented with the history of trauma, we did not take into consideration a proximal femoral malignancy. However, Ungureanu et al. stated in their study that tumoral growths can be kept hidden under adipose tissue or local swelling located at the thigh level and they could appear concurrently with trauma 3. Therefore, the differential diagnosis was made using the patient history and the CT description given by the radiology specialist. A standard emergency anteroposterior radiograph revealed an intertrochanteric fracture, severe deformity of the left hip joint, and the migrated implants used for the arthrodesis (Fig. 1). Computed tomography (CT) imaging of the left hip joint showed a displaced intertrochanteric fracture distal to the ankylosed hip joint, some artifacts due to the osteosynthesis material, and marked atrophy of the gluteus muscles (Fig. 2). Due to the rarity of the pathology, several discussions with fellow surgeons were needed to establish what the best therapeutic option was. We decided to perform a surgery to remove the osteosynthesis material used for arthrodesis of the left hip and then perform the internal fixation using a locking plate and locked screws (Fig. 3). The patient was positioned in dorsal decubitus; we used a lateral approach (a skin incision reaching approximately 5 cm proximal and 15 cm distal from what used to be the tip of the greater trochanter). Intraoperative passive mobilization of the limb was realized to outline some intraoperative anatomical landmarks. After initial hardware removal, normal femoral rotation was re-established and checked intraoperatively using the C-arm. A rigid secondary fixation was realized using a locked plate and 13 locking screws. Postoperatively, the patient's evolution was good, and after 2 weeks, she could walk using double crutches. Postoperatively after 3 months, the fracture showed signs of consolidation.",
"gender": "Female"
}
] |
PMC5771915
|
[
{
"age": 63,
"case_id": "PMC6267726_01",
"case_text": "A 63-year-old woman with short stature (148 cm) was admitted because of a sudden onset confusion. One week ago, the patient started developing auditory and visual hallucinations, as well as disorganized speech. She was unable to communicate at that time. However, symptoms improved without treatment 1 day later. Her past medical history was notable for well-controlled hypertension and diabetes mellitus. She had a history of \"cerebral infarction\" 2 years ago and developed stroke-related psychotic symptoms including agitation and confusion. With the diagnosis of stroke at that time, she was treated then and improved afterward. For family history, her older sister died from \"stroke\" at the age of 45. Her mother also died at an early age for unknown reasons.\nThe neurological examination was unremarkable except for bilateral hearing loss and bilateral positive Babinski sign. Routine laboratory investigations revealed no abnormalities excepted for a slightly elevated creatine kinase (214 U/L, reference range: 15-195 U/L). The head computed tomography scan on admission showed a lesion with low density in the left occipital lobe. The diagnosis of ischemic infarction was given considering the patient's presentation and a history of hypertension and diabetes mellitus. Treatment with aspirin and atorvastatin was started. Brain MRI afterward, however, showed a lesion in the left temporal-occipital lobe with long T1 and T2 signals, and high signals on flow attenuated inversion recovery (FLAIR) sequence (Figure 1) as well as a slightly increased signal on diffusion weighted imaging (DWI). The brain magnetic resonance angiography was normal. Unexpectedly, the patient's symptoms suddenly deteriorated 2 weeks after admission. She developed acute psychosis and right-sided hemiparesis (muscle strength of the right limbs 1/5). Mixed nonfluent aphasia was also identified on further evaluation. The patient underwent another MRI showing lesions with abnormally high signals on FLAIR and DWI with poorly defined margins along the gyri in the left occipital-temporal lobe, which was slightly enhanced after gadolinium enhancement (Figure 2). Similar episodes of psychotic symptoms and aphasia relapsed five times ever since, each lasting hours to days, and she completely recovered every time. Other tests including cerebrospinal fluid examination, autoimmune encephalitis-related antibodies, and long-term electroencephalography were nonrevealing.\nOn further investigation of the history, the patient recalled a progressive decline of bilateral hearing from 2 years ago and was almost deaf since last year. The lactate of venous blood was measured, showing 3.7 mmol/L at rest (reference range: 0.5-2.2 mmol/L), and the lactic acid after exercise was not obtained because the patient refused to undergo further investigations. The patient was suspected of mitochondrial disease due to the combination of recurrent stroke-like episodes, short stature, hearing loss, and an elevated lactic acid at rest. The blood genetic test suggested a low-frequency (<20%) mutation of m.3243A.G. After being treated with arginine, vitamin E, and coenzyme Q10 for 1 week, the patient dramatically improved. The muscle strength recovered, and there were no residual psychotic symptoms or aphasia on discharge.\nThis case study was approved by the institute ethics committee of the Hangzhou Red Cross Hospital. Written informed consent was obtained from the patient to publish the case details.",
"gender": "Female"
}
] |
PMC6267726
|
[
{
"age": 10,
"case_id": "PMC7661465_01",
"case_text": "A 10-year-old previous health boy was presented with intermittent dyspnea and chest pain over one month without syncope. His older brother was diagnosed with cardiomyopathy in 2001, characterized with enlarged right ventricle and perforated RV, and suddenly died at 16 years old after running in 2007. His mother occasionally had chest tightness. Her ECG reveals T wave inversion in leads of III, V1,V2, and V3, and her Echo revealed a slight decrease of diastolic function, other measurements are in normal range.\nAbout one month ago, he felt labored dyspnea, and 1 week later he was diagnosed with myocarditis in a local hospital and treated with digoxin, diuretic and myocardium nutrition. Then his symptom released. One week after that, he had dyspnea again and 10 days later was admitted in our pediatric cardiology department. Physical examination showed he was in a general state, Heart Rate 88 bpm, Respiratory Rate 19 bpm, BP 112/72 mmHg, weight 44 kg. No edema on the face and legs, heart sounds strong, without murmur, but rhythm was irregular, auscultation revealed 5 premature beats in 1 min. The liver was 3 cm below right costal margin. Admission blood test revealed normal cTnI, hs-cTnT, CK-MB mass, and NT-pro BNP. Echo showed the right ventricular (RV) was significantly dilated (RV diameter 31.8 mm), RVED/LVED = 0.67, the wall of the RV became thinner, interwoven reticular muscle fiber structure can be seen in the RV (Figure 1). ECG showed epsilon wave and paired PVC (Figure 2a). Holter showed paired PVC and premature atrial contractions (PAC). Cardiac magnetic resonance imaging (CMRI-in local hospital) revealed a dilated right ventricular outflow tract, thin right ventricular wall with reduced wall motion, and foci of fatty deposit in the right ventricular free wall (Figure 1). Genetic testing finds DSG2 mutation (R49H), which has been indicated to be associated with ARVC. The patient was diagnosed of ARVC.\nHis father rejected the prescription of betaloc as a treatment for its side effect in reducing sexual function. The patient was treated with aspirin (50 mg, qd po), propafenone (200 mg, q8h), enalapril (5 mg qd), furosemide (20 mg qd, oral 4 days a week), and spironolactone (20 mg qd, oral 3 days a week). At admission, his ECG showed QRS was nearly normal, 118 ms (Figure 2a). QRS duration in this article is measured with V5 andII leads. But on the second day after taking oral propafenone, he developed dizziness and his ECG showed QRS was 158 ms. On third day of oral propafenone, QRS was increased to 170 ms (Figure 2b). We reduced the dose of propafenone by half, and on next day, QRS was reduced to 120 ms (Figure 2c). After 1 month treatment, his ECG showed QRS was 164 ms. Therefore, we discontinued propafenone and replaced with sotalol (80 mg, q12 h), and gradually increased the dose to 120 mg. q12 h. At 3 month of illness, QRS was 114 ms; AECG showed PVC 3001/d with paired PVC. Sotalol was then reduced to 80 mg q12 h. At 6 months of illness, QRS returned to normal:ECG showed QRS was 124 ms (Figure 2d). The boy felt better, and the symptoms of dyspnea and chest pain were released.",
"gender": "Male"
}
] |
PMC7661465
|
[
{
"age": 17,
"case_id": "PMC2787018_01",
"case_text": "A 17-year-old male was referred to the pediatric gastroenterology clinic due to elevated transaminases noted during standard screening blood work. The patient had a history of type I diabetes mellitus (T1DM) diagnosed since 5 years of age with the patient having multiple hospital admissions for diabetic ketoacidosis secondary to noncompliance with insulin therapy. Past medical history was significant for pyloric stenosis repair at 4 weeks of age and a prior history of tonsillectomy and adenoidectomy. Family history was noncontributory. His current medication consisted of Humalog Mix 75/25 insulin (Eli Lilly and Company) with the patient receiving approximately 1.3 units of insulin per kilogram body weight. \nThe patient had no history of jaundice or scleral icterus, and he denied right upper quadrant pain, pruritis, weight loss, ascites, hematemesis, or rectal bleeding. A review of his blood glucose monitoring demonstrated a range of 250-310 milligram per deciliter (mg/dL), and he had a hemoglobin A1c of 12.3% suggesting poor glycemic control. \nA liver ultrasound showed normal hepatic echotexture and minimal sludge in the gallbladder (Figure 1). A complete blood count, prothrombin time, activated partial thromboplastin time, lipid panel, free thyroxine level, and tissue transglutaminase serum IgA level were normal. However, transaminases were elevated with an aspartate aminotransferase (AST) and alanine aminotransferase (ALT) consisting of 63 international units per liter (IU/L) and 209 IU/L, respectively. Direct bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase levels were normal. A viral hepatitis panel, serum ceruloplasmin, and alpha 1-antitrypsin phenotype were normal. The patient was noted to have an elevated ANA titer (1 : 160 in a homogenous pattern). Screening for smooth muscle antibody was negative, and it was decided that a percutaneous liver biopsy should be performed due to the possibility of type 1 autoimmune hepatitis. \nA subsequent liver biopsy demonstrated normal portal tracts (H&E 100x, Figure 2(a)); however, hepatocytes demonstrated cytoplasmic clearing secondary to increased intracellular glycogen and microvesicular fat (H&E 200x, Figure 2(b)). This biopsy was consistent with Mauriac syndrome and the importance of improved adherence to insulin therapy was expressed to the patient and his family.",
"gender": "Male"
}
] |
PMC2787018
|
[
{
"age": 66,
"case_id": "PMC7391113_01",
"case_text": "A 66-year-old man was admitted to our hospital with complaints of severe pain in the abdomen, which persisted for over 48 hours. The medical history included a splenectomy after trauma and a posttotal gastrectomy for gastric cancer. On admission, tenderness and involuntary guarding were observed in all quadrants of the abdomen. Additionally, the patient developed fever (temperature of 39 C) and was hemodynamically unstable with a blood pressure of 90/50 mm Hg and a heart rate of 120 bpm. On physical examination, skin discoloration was observed around the right side of the abdomen with tense edema. Laboratory tests revealed a C-reactive protein level of 18.0 mg/dL (range, 0-0.30 mg/dL), white blood cell count of 2700/mm3 (range, 3300-8600/mm3), and an elevated serum creatine kinase level of 1977 U/L. Abdominal contrast-enhanced computed tomography (CT) showed fluid collection, an air pocket in the subcutaneous fat layer of the abdominal wall, and edematous changes in the adipose tissue in the peritoneum and abdominal wall (Figure 1(a)). Inflammatory changes were observed around the ascending colon (Figure 1(b)). Based on a diagnosis of peritonitis resulting from a perforated ascending colon, an emergency operation was performed. Extensive necrosis of the retroperitoneal fat was observed around the ascending colon where the inflammation was severe. In addition, necrotizing fasciitis was suspected in the abdomen due to an infection caused by the perforated ascending colon. The patient was immediately managed with an intravenous administration of a broad-spectrum antibiotic (meropenem at 1.5 g/day). A right hemicolectomy, ileostomy construction, and debridement of necrotic tissues were performed (Figure 2(a)). The stump of the ascending colon was closed without colostomy. The pathological findings of the resected specimen revealed peritonitis and ischemic changes, and the ascending colon was noted to be very thin; however, no malignancy was detected. (Figure 2(b)).\nTwo days following the initial operation, the skin discoloration around the right side of the abdomen reappeared, which indicated widespread necrosis of the abdominal wall fascia (Figure 3(a)). The follow-up CT showed necrotizing fasciitis spreading up to the right lateral chest wall, along the right lateral abdominal wall, and extending to the right groin. A second operation was performed, and the necrotic tissue was debrided from the level of the right abdominal wall to the damaged skin and subcutaneous tissue on the right side of the chest wall (Figure 3(b)). This resulted in a significant abdominal wall defect. The intestine, inferior vena cava, and right kidney were exposed (Figure 3(c)). A closure of the wound defect was planned using the ABThera System to remove exudate and promote wound healing (Figures 4(a)-4(d)). Under local anesthesia, repeated surgical debridement was performed, and the NPWT dressing was changed 3 times a week for 4 weeks. Following the application of NPWT set at 125 mmHg of continuous negative pressure, extensive debridement and NPWT successfully contributed to the wound bed healing. The size of the open wound with visible granulation tissue significantly reduced with no complications such as an enteric fistula (Figures 5(a)-5(c)). After 4 weeks of NPWT, the wound beds were sufficiently developed for plastic surgery. Finally, the defect in the abdominal wall was covered by a mesh split-thickness skin graft and an anterolateral thigh flap (Figure 5(d)). The patient was discharged 63 days after admission and was regularly followed up at the outpatient department for 6 months without complications (Figure 6).",
"gender": "Male"
}
] |
PMC7391113
|
[
{
"age": 76,
"case_id": "PMC4763553_01",
"case_text": "A 76-year-old male with a past medical history of coronary artery disease, status post coronary artery bypass graft and chronic anemia presented to the emergency department after he developed episodes of chest pain and pre-syncope. He denied any non-steroidal drug or alcohol use.\nOn presentation, he was normotensive with a sinus tachycardia. His hemoglobin was 6.1 mg/dL, and the platelet count was 202.0 mg/dL. Initial fecal occult blood test was negative. He received multiple blood transfusions for his symptomatic anemia with a goal hemoglobin of greater than 7.0 mg/dL. There was a transient increase in his hemoglobin. A computerized tomography (CT) scan of the abdomen and pelvis without contrast did not reveal any bleeding source.\nThe following day the nurse witnessed him having a significant amount of hematochezia. Subsequent upper and lower endoscopy was done that revealed two 5 mm blue venous blebs in the esophagus and multiple patches of blue venous blebs throughout the colon (Figs. 1 and 2). Given the absence of active bleeding, no endoscopic intervention was undertaken. Through the course of his hospitalization, the patient received a total of five units of blood. He was managed medically with oral iron and periodic monitoring of his hemoglobin.\nOne year after initial diagnosis, the patient is doing well on oral iron supplementation, and his hemoglobin is being closely monitored by his primary care physician.",
"gender": "Male"
}
] |
PMC4763553
|
[
{
"age": 68,
"case_id": "PMC3546216_01",
"case_text": "One month before visiting our pain clinic, a 68-year-old female patient with vesicles and pain on the left side around the navel was diagnosed with herpes zoster and received treatment at a local hospital. Although the skin rash improved, the patient, at times, felt squeezing sensations on her left flank. When the patient was referred to the pain clinic, the patient had a squeezing pain and scars of vesicles on the T10 dermatome level on the left side and her numeric rating scale (NRS) was 5 (out of 10). She felt the squeezing pain several times for approximately one minute each time. Aside from a history of hypertension, there was no other unusual medical history or a history of prior surgeries. She was 152 cm tall and 51.2 kg in weight. Laboratory examinations showed no signs of bacteria or viral infection. Complete blood cell count, prothrombin time and activated partial thrombin time tests showed normal results, and there were no abnormal results in the serologic tests (HBs Ag/Ab, HIV Ag/Ab, quantitive VDRL).\nAfter diagnosis of postherpetic neuralgia, the patient received an epidural block once a week for a total of six weeks. We performed the epidural block with 8 ml of 0.8% mepivacaine with the paramedian approach to T10-T11 with the 'loss of resistance' method. Out of six total procedures, only the first procedure included 20 mg of triamcinolone with local anesthetics, and the rest were composed of local anesthetics only. Any signs or symptoms suggestive of dural puncture, such as cerebrospinal fluid (CSF) aspiration through the block needle, headache, paresthesia or sensory impairment were not observed during each epidural block. Pregabalin 150 mg and amitriptyline 5 mg were also prescribed for twice a day. After each epidural block, a pain free period continued for two or three days but she felt numbness like prior to the procedure. Additionally, the squeezing pain reappeared but the pain intensity was reduced to NRS 3. Thus, we expected full recovery by repetitive epidural blocks and by an additional root block or transforaminal epidural block.\nTwo days after the sixth epidural block, the patient was admitted to the department of neurology, through the emergency department, because the patient felt continuous dizziness and motor weakness in both lower extremities. Five days prior to receiving the sixth epidural block, the patient began to feel slightly dizzy. However, the continual dizziness became extreme by the time the patient was admitted to the hospital. Motor weakness of the lower extremities was felt by the patient two days after the final epidural block. In addition, the patient had symptoms of nausea and vomiting. The patient also could not stand or walk alone. The patient's body temperature was 38.3C and she did not have any abnormalities on her skin. Physical examination showed a grade III motor weakness in both of the lower extremities, but the deep tendon reflex and cerebellar function tests were normal. Sensory impairment was not observed. She was referred to our pain clinic, because a complication during an epidural block was considered by neurologists. We reviewed the sixth epidural block, examining for any evidence of dural puncture, aspiration of blood and other abnormal events, but there were none. However, in order to be certain, we performed Magnetic Resonance Imaging (MRI) and CSF tests on the first day of admission. The MRI showed no signs of hematoma, abscess, or arachnoiditis (Fig. 1). No bacteria were detected upon CSF analysis. Considering the results, we were able to exclude the possibility of an epidural block complication. The CSF analysis results showed, however, a mild increase in the WBC count (49,000 count/mm3) and a protein level of 97 mg/dl. Virus serology test of the blood and the CSF showed negative anti-IgG and negative anti-IgM antibodies for herpes simplex virus (HSV) and herpes zoster. Two days after the patient was admitted, the patient complained of urinary difficulty and a Foley catheter was inserted, resulting in discharge of 1,200 ml of urine through the catheter. The patient felt squeezing pain on the T10 dermatome level on the left side during her entire stay at the hospital.\nConsidering her clinical progressions and the increase in protein level in the CSF analysis, herpes zoster myelitis was diagnosed by the neurologist and appropriate treatments commenced. Three days after the patient was admitted, the patient was given intravenous acyclovir 1.6 g and dexamethasone 20 mg daily for two weeks. The patient also received exercise rehabilitation treatment while she was on the medication. After receiving treatment for one week, the patient was able to walk but had difficulty in standing up. The patient showed gradual improvement and four weeks later made a full recovery in motor function. The patient's urinary difficulty improved through urinary training and she fully recovered in eight weeks.",
"gender": "Female"
}
] |
PMC3546216
|
[
{
"age": 57,
"case_id": "PMC3350111_01",
"case_text": "The patient was a 57-year-old female who presented to the trauma bay of a university trauma center via intrafacility transfer after a motor vehicle collision in which her vehicle rolled down an embankment. She was hemodynamically stable and with a Glascow Coma Score of 15. Computed tomography of her chest abdomen and pelvis revealed an aortic injury consistent with transection and left hemothorax with associated atelectasis. Her blood pressure was stable, and her hemoglobin and hematocrit were within normal limits. She had several comorbidities which included chronic obstructive pulmonary disease, diabetes mellitus, hepatitis C, hypertension, history of thyroid cancer status post thyroidectomy, and asthma. \nShe was admitted to the surgical critical care unit for strict blood pressure control and went to the endovascular suite with vascular surgery the following morning for a thoracic endovascular graft repair of the aortic injury. The case resulted in a midline laparotomy after deployment of the graft, lengthy lysis of adhesions, injury to the left gonadal vein resulting in one liter of blood loss, and finally retroperitoneal dissection and exposure of the infrarenal aorta and iliac arteries. Due to the extensive calcifications of the iliac vessels, the aorta was cannulated and the stent graft was deployed. Her abdomen was closed, and she was returned to the critical care unit.\nThe patient's course in the critical care unit was long and complicated to include acute respiratory distress syndrome and prolonged mechanical ventilation. Due to high oxygen and positive end-expiratory pressure requirements, patient did not undergo a tracheostomy until hospital day number twenty-four. She subsequently had a PEG tube inserted a few weeks later. We continued to attempt to wean the patient from mechanical ventilation. Her Glasgow Coma Score improved significantly over the following weeks to the point she was alert and able to follow commands, attempting to verbalize. However, when patient was placed on tracheostomy collar trials, she became very anxious and tachypneic. This was felt initially to be due to anxiety. After several days of similar symptoms despite anxiolytics, patient developed a wheeze. She had no changes in her chest radiograph. We decided at that time to perform a flexible bronchoscopy and found tracheal collapse distal to the tracheostomy tube.\nWe ordered a dynamic computed tomography scan of the chest to evaluate the extent of the tracheomalacia. Imaging revealed significant collapse of the distal trachea and main stem bronchi. It was decided to take her for video bronchoscope, rigid bronchoscopy, Dynamic Y-stent placement, and exchange of tracheostomy tube with a regular Shiley size 8 tracheotomy tube (Figure 3).\nVideobronchoscopy was performed through the distal XLT (Extended Length) tracheostomy tube, and severe tracheobronchomalacia was noticed. The patient had almost complete collapse of the trachea distal to the tracheostomy tube and almost complete collapse of the left mainstem bronchus. Distal XLT tracheostomy tube was exchanged to regular Shiley size 8 tracheostomy tube. Videobronchoscopy was performed through the newly placed Shiley tracheostomy and measurements for the Y-stent taken. Rigid bronchoscopy was then done to ascertain that patient was rigidly intubatable for the deployment of dynamic Y-stent (Figure 2). After successful rigid bronchoscopy Y-stent was deployed under fluoroscopic guidance. The Y-stent limbs were well seated in the trachea left main stem bronchus and right main stem bronchus. \nPostoperatively patient did well and was able to be weaned from mechanical ventilation. At three-month followup, patient is doing well with tracheostomy and stent in place. The plan is to follow the patient for stent and/or tracheostomy removal or replacement.",
"gender": "Female"
}
] |
PMC3350111
|
[
{
"age": 81,
"case_id": "PMC9705577_01",
"case_text": "Our patient is an 81-year-old female was referred to our clinic by her endocrinologist after noticing that her right thyroid nodule had increased in size over the last 6 months. She has a medical history of renal cell carcinoma, hyperlipidemia, and type 2 diabetes. She had previously undergone an L nephrectomy in 1999 and a hysterectomy in 1990. She denied any previous use of tobacco, alcohol, or illicit drugs. She had a family history of stomach cancer in her mother.\nThe original pathological diagnosis was mixed clear/granular cell adenocarcinoma, which is now labeled clear cell renal cell carcinoma (CC-RCC). At the time of diagnosis, the tumor was confined to the kidney, without angiolymphatic invasion. The nuclei were given a Fuhrman grade 4 due to the bizarre and often multinucleated nuclei, with heavy chromatin clumps and prominent nucleoli. One lymph node was examined and found to be negative for malignancy. Because the tumor was 7.8 cm in greatest dimension and limited to the kidney, it was a pathologic stage pT2a. In November 2016, the patient underwent a fine needle aspiration of her right thyroid. The specimen was adequate with follicular epithelial cells and scattered colloid, consistent with a benign follicular nodule. There was no evidence of malignancy; however, sampling bias is always an issue.\nWith the recently reported increase in size, a repeat ultrasound was completed by her endocrinologist, and she was found to have a large right-sided nodule that was hypervascular measured 5.7 x 3.4 x 4.5 cm, and had increased in size from her previous ultrasound in 2018. She also noted occasional dysphagia. Her thyroid function testing reported normal levels of thyroid stimulating hormone and thyroxine. She denies any hoarseness or difficulty breathing. She was notified during the examination that she has a large nodule within the right thyroid that was irregular but without tenderness.\nThe patient underwent a right-lobe partial thyroidectomy in June 2020. The history of CC-RCC was noted in previous pathology reports. The gross examination of the resected specimen demonstrated a \"well-circumscribed golden-yellow-tan mass\" in which there were areas of hemorrhage present. Histologic sections showed a partially encapsulated, nodular proliferation composed of monotonous, intermediate-sized cells, embedded within benign thyroid parenchyma (Figure 1). At higher power examination, the mass is composed of clear cells with centrally located nuclei, prominent nuclei, and abundant vascular capillary network (\"chicken wire\") characteristic of clear cell renal cell carcinoma (Figure 2). Immunohistochemical stains were performed to further evaluate the site of origin for the neoplastic cells. The renal markers PAX8 and RCC were positive, while the parathyroid and thyroid markers (PTH and TTF1) were negative. Pancytokeratin was focally reactive and the neuroendocrine marker synaptophysin was negative excluding an endocrine neoplasm. The morphologic and immunohistochemical features of this neoplasm, along with her known history, were most consistent with metastatic clear cell renal cell carcinoma.\nThe patient's PET/CT scan did not demonstrate any signs of residual or metastatic disease. Due to her advanced age and the 21 years between her initial disease and metastatic disease, our multidisciplinary tumor board elected to observe the patient with repeat PET in 4 months and not initiate chemotherapy at this time.",
"gender": "Female"
}
] |
PMC9705577
|
[
{
"age": 12,
"case_id": "PMC7687474_01",
"case_text": "Mao et al. reported 36.4% of the 214 study participants hospitalized with COVID 19 had neurological manifestations. In our knowledge, there have been seven cases of Guillain-Barre syndrome [GBS] reported so far with five in Italy, one in Iran and one in the United States in patients with COVID 19 infection. In Italy, the first symptoms noted were lower limb weakness and paresthesia in four patients and facial diplegia followed by ataxia in one patient with symptoms of GBS occurring within 5-10 days from first onset of symptoms of COVID 19. Virani et al. reported a SARS-CoV-2 positive patient who developed progressive, ascending weakness consistent with GBS while in Iran is where the first case was reported describing symptoms of GBS in an infected patient with COVID 19. GBS is an acute immune mediated demyelinating disease which is progressive, ascending, symmetrical and involves flaccid paralysis of the limbs with areflexia or hyporeflexia with or without cranial nerve involvement with history of preceding respiratory or gastrointestinal infection 2-4 weeks prior in two third of cases. In this report, we describe GBS symptoms in a 12 year old infected patient with COVID-19 for the first time in Tanzania and Africa as a whole.",
"gender": "Unknown"
},
{
"age": 12,
"case_id": "PMC7687474_02",
"case_text": "LB, 12 year old young man presented to the Emergency Department with symptoms of acute progressive symmetric ascending quadriparesis with bilateral facial paresis. He was asymptomatic a week prior and then he developed a low grade fever and a dry cough. He was managed conservatively and treated symptomatically. He complained of lower back pain 5 days prior to arrival to the ED which was rapidly followed by weakness of both lower limbs. He was able to walk initially and was taken to a local dispensary where he was administered an intramuscular analgesics and discharged. The next morning, he lost function of both lower limbs with associated weakness of bilateral upper limbs as well and could not get out of bed and this prompted the family to seek further medical attention. He was taken to the same facility again and advised to start physiotherapy with a provisional diagnosis of lumbar spondylitis. He was referred when he developed facial paresis bilaterally and an altered level of consciousness associated with an increased respiratory rate. In the emergency department, the mother provided the additional information of the low grade fever and cough from the week before which they had managed conservatively at home. There was no history of recent travel or contact with a positive case of COVID 19. There was no significant past history or any known co-morbidities.\nVital signs on presentation were remarkable with a respiratory rate of 24 breaths per minute with oxygen saturation of 88% [hypoxic] on room air with a heart rate of 150 beats per minute and a blood pressure of 150/100 mmHg. The patient was barely conscious with a Glasgow Coma score of 6/15 and had signs of shock with cold extremities and diaphoresis. The child was placed on nasal prongs at 6L of high flow oxygen and connected to a cardiac monitor. Blood was drawn for lab investigations, an ECG was done and a chest X-ray ordered. Physical examination revealed decreased lower extremity strength and muscle tone compared to upper extremities with a score of 1/5 in lower extremities versus a score of 2/5 in upper limbs as per Medical Research Council [MRC] scale. Deep tendon reflexes were absent in all four limbs. Meningeal irritation signs and upper motor neuron disorder signswere absent. The bedside blood glucose was 11.0 mmol/L. His lab results showed a white blood cell count of 17.3 x103 cells/mL, hemoglobin of 14.6g/dL and platelet count of 361 x 103 cells/mL with an otherwise normal differential. Electrolytes and renal profile were within normal ranges with a blood urea nitrogen of 5.6 mmol/L, creatinine of 54.4micromol/L, sodium of 142, potassium of 4.6 and chloride 100. Chest X-ray revealed bilateral basilar opacifications suggestive of consolidation with diffuse infiltrates bilaterally. ECG showed a sinus arrhythmia with slightly tall and tented T waves (Figure 1). Bedside ultrasound revealed good cardiac contractility with a full Inferior vena Cava [IVC] and no pericardial or pleural effusion.\nGiven the existing epidemiological scenario and preceding symptoms of fever and cough, COVID-19 infection was suspected. Appropriate isolation precautions were implemented, and a respiratory viral panel testing [nasopharyngeal PCR] was sent. Antibiotic coverage was done empirically and other treatment modalities done as required. Just prior to transfer to Pediatric Intensive Care [PICU], child lost pulse and Cardio-Pulmonary Resuscitation [CPR] was initiated with return of spontaneous circulation [ROSC] achieved within 1 cycle of the CPR. Child was intubated and ventilated and started on positive inotrope infusion. A diagnosis of GBS was made and patient was immediately started on 400mg/kg of intravenous immune globulin [IVIG] therapy for a planned 5-day course according to clinical manifestations related to GBS. The reverse transcription-polymerase chain reaction [RT-PCR] for COVID-19 was positive and further evaluation and management was continued in the ICU. Given the classic clinical picture of GBS in absence of other identifiable etiology for his neurologic disease and strict infection control measures, additional supportive testing was not pursued. His clinical course showed improvement in his respiratory status, neurological status as well as his consciousness level with an improvement of the GCS to 14/15 within 5 days. Neurologically, his upper extremity weakness resolved after completion of the course of IVIG. Lower extremity power and tone improved significantly. He was planned for weaning off ventilation and extubation on day 6, and eventual rehabilitation and discharge. During the night preceding the planned weaning, the child self extubated accidentally and rapidly decompensated. Cardiac arrest ensued and attempts to resuscitate after CPR were futile and child died.",
"gender": "Male"
}
] |
PMC7687474
|
[
{
"age": 5,
"case_id": "PMC3535818_01",
"case_text": "We present a case of a five-year-old boy who presented with a slightly raised, painless lesion on base of the nose near the medial side of a the left eyebrow (Figure 1) since 6 months. On examination, there was nontender, firm nodule, measuring 0.5 cm in diameter. A fine needle aspiration cytology (FNAC) was performed with 23 G needle, and provisional diagnosis of mesenchymal neoplasm was rendered. The patient was advised excision biopsy for final diagnosis and behavior of neoplasm. Subsequently an excision biopsy was performed, and final diagnosis of DFSP was made based on the histopathological findings. \nThe patient was then advised reexcision surgery with wide margins. Patient was lost to followup and later turned up after two months with recurrence of similar swelling at same site.\nPathological Finding: May-Grunwald Giemsa (MGG) stained cytological smears showed scanty cellularity comprising few cohesive clusters and singly dispersed oval to spindle cells in hemorrhagic background (Figures 2 and 3). Tumor cells had oval hyperchromatic nuclei, inconspicuous nucleoli, and poorly defined cytoplasmic borders (Figure 2 inset). Provisional diagnosis of mesenchymal neoplasm was rendered. The patient was advised excision biopsy. \nSubsequently an excision biopsy was performed. We received tiny skin covered soft tissue, measuring 0.8 x 0.6 x 0.4 cm. Hematoxylin and eosin stained sections showed cellular and poorly circumscribed tumor in the dermis comprising interwoven bundles and fascicles of uniform spindle shaped cells arranged in \"storiform\" or \"cartwheel\" pattern (Figure 4). The tumor cells had monotonous appearance with oval nuclei, vesicular chromatin, inconspicuous nucleoli, and scanty to moderate cytoplasm (Figure 4 inset). The mitotic activity was moderate (3-5/10HPF). The tumor was seen infiltrating into the underlying subcutis. Diagnosis of DFSP was made. A panel of immunohistochemistry (IHC) comprising vimentin and CD-34 was applied. Tumor cells were positive for both vimentin and CD-34 (Figure 5).",
"gender": "Male"
}
] |
PMC3535818
|
[
{
"age": 23,
"case_id": "PMC5937516_01",
"case_text": "A 23-year-old male presented to the primary care clinic to establish care after relocating to Arizona. His past medical history was significant for severe, mostly spontaneous, keloid formation since puberty. He complained of a right ring finger mass and a left ring finger deformity, bilateral foot pain, and worsening keloids and skin nodules.\nOver the last four months, he had noticed a spontaneous, slowly enlarging mass on his right ring finger. It bothered him when directly pressed upon or during rock climbing. There were no associated neurological symptoms, redness, or erythema. He also reported a contracture in the left ring finger over the last six months. He had undergone a left small finger proximal interphalangeal joint arthrodesis for presumed camptodactyly at age 16. This surgery was complicated by fibromatosis and keloid scar formation, ultimately leading to amputation of the small finger. He now complained of excessive scar formation at that amputation site.\nHe gave a two-year history of bilateral forefoot pain. His right fourth toe was the most painful. He reported that this toe had become very stiff over this time. Other toes were involved as well, and prolonged standing exacerbated the symptoms. He did not report any redness, warmth, or swelling. He denied any acute joint pain episodes and hand or back pain.\nWith respect to his keloids and skin nodules, he had had them since puberty. He noted that some were related to sites of minor trauma, and others were spontaneous. He had multiple large keloids involving the chest, back, arms, and legs. Recently, some had involved the toes as well. He denied any genital involvement. Past treatments included intralesional steroid injections and radiation therapy with temporary improvements.\nHe was a lifelong nonsmoker and drank alcohol socially. He was an avid rock-climber. His family history was significant for keloid formation in his grandfather. A maternal cousin had rheumatoid arthritis. On review of systems, he denied any fatigue, morning stiffness, night sweats, weight loss, inflammatory eye disease, cough, shortness of breath, back pain, nephrolithiasis, Raynaud's phenomenon, or blood dyscrasias. He did not take any chronic medications.\nOn examination, he was afebrile with normal vital signs and appropriate weight. There was no glandular swelling or gingival hypertrophy. Hand examination showed severe left ring finger proximal interphalangeal (PIP) joint contracture of 80 , with palmar fibromatosis and keloid scar formation (Figures 1 and 2). There was no intrinsic degeneration of the PIP joint on X-ray or MRI. The right ring finger demonstrated a firm and immobile mass extending for the length of the middle phalanx on the ulnar aspect. Ring finger movement was intact. At the distal aspect of his prior amputation, he had a thickened scar. Mild tenderness to flexion and extension of his bilateral fourth and fifth digits was present. He had prominent fifth metatarsal heads bilaterally which were tender to palpation. Ankle and subtalar joint exam was normal. Ambulation was unrestricted. Multiple large areas of hypertrophic scarring and keloid formation involving the central chest (Figure 3), arms, and legs as well as some discrete nodules on the upper back were present.\nLaboratory testing was unremarkable. He tested negative for rheumatoid factor, anticyclic citrullinated peptide, C-reactive protein, erythrocyte sedimentation rate, anti-nuclear antibody, HLA-B27 gene, and hepatitis serology. Routine laboratory markers including complete blood count, renal function, liver function, thyroid and parathyroid gland function, and uric acid and urinalysis were normal. A chest radiograph was unremarkable. A right hand X-ray film showed nonspecific soft tissue swelling of the right ring finger. The left hand film showed amputation of the small finger at the level of the proximal to mid fifth metacarpal and a flexion deformity of the ring finger at the PIP joint. Sacroiliac joints showed minimal degenerative changes on X-rays. Feet radiographs showed multiple erosions. Axial (Figure 4) and coronal (Figure 5) magnetic resonance imaging (MRI) of the feet obtained with gadolinium contrast administration demonstrated marginal erosions, synovitis, and bone marrow enhancement. Enhancing inflammatory changes in the plantar soft tissues and heterogeneous enhancement of keloids was also seen.\nTo treat the contracture, the patient underwent a left ring finger palmar fasciectomy. Operative findings included severe fibromatosis of the left middle and ring finger and keloid formation that was confirmed by histopathology. After excision of diseased palmar fascia, the finger was able to be fully extended. A residual skin deficit required skin grafting for closure. The entire palmar surface of the proximal phalanx was resurfaced with a full thickness skin graft. His nonoperative skin lesions were treated with a combination of intralesional methylprednisolone, 5-fluorouracil, and pulsed dye laser treatments. He was initiated on 15 mg of oral methotrexate for his erosive disease.\nAggressive occupational therapy was pursued after the surgery. At six-month follow-up, he reported improvement in his joint pain as well as keloids. The ring finger PIP joint flexion contracture had improved from 80 to 35 . However, continued keloid formation persisted over the surgical scars. His skin graft healed completely. Due to the scarring and keloids, no further surgery was recommended.",
"gender": "Male"
}
] |
PMC5937516
|
[
{
"age": 73,
"case_id": "PMC6116301_01",
"case_text": "A 73-year-old female with a past medical history of a previous cerebrovascular accident, breast cancer, and vulvovaginal adenocarcinoma was admitted for diplopia and generalized weakness. Regarding the patient's malignancy history, she was diagnosed with advanced stage vulvar cancer 8 years previously and underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy the following year. She was diagnosed with left breast cancer the following year and underwent breast conservation surgery and radiotherapy. She was placed on anastrazole therapy thereafter and followed regularly with her oncologist. Her recent imaging studies did not demonstrate new disease.\nThe patient's initials symptoms were irritation of her left eye, and after seeing her primary care provider, she was started on tobramycin eye drops (0.3% solution, every 2-3 h) for a possible ocular infection. Three days after initiating tobramycin she began experiencing diplopia, generalized weakness (primarily in the neck), and increasing respiratory distress. The patient did not recall ever having symptoms like this before and denied a history of MG. Her laboratory studies were significant for AchR-binding antibody positive at 82 nmol/L, AchR-blocking antibody positive at 56% inhibition, AchR-modulating antibody positive at 95% inhibition, and a positive striate muscle antibody titer of 1:160. A computed tomography of her chest did not show the presence of a thymoma in the mediastinum.\nThe patient was started on pyridostigmine therapy with improvement of her symptoms. However, while she initially responded well to pyridostigmine, she begin experiencing increasing weakness and fatigue after receiving intravenous and oral magnesium the following day, despite an increase in the dosage of pyridostigmine. She subsequently underwent six cycles of plasma exchange therapy with improvement in her symptoms however she did not tolerate nasal cannula for long periods of time. She continued to require pressure support ventilation via facemask throughout her admission. Her long-term plan was to undergo weekly PLEX therapy for 3-6 months at a long-term acute care facility, with continued ventilator support through a tracheostomy.\nUnfortunately the patient's clinical status continued to deteriorate as she developed an upper GI bleed, developed a significant anemia due to blood loss, and was intubated for respiratory failure due to prolonged periods of apnea. Shortly thereafter she went into a pulseless electrical activity cardiac arrest and underwent 30 min of cardiopulmonary resuscitation. Her family made the decision to withdraw care and she died shortly after.",
"gender": "Female"
}
] |
PMC6116301
|
[
{
"age": 23,
"case_id": "PMC6180860_01",
"case_text": "Phyllodes tumour was first described in 1838 by Johannes Muller. These tumours are uncommon and comprise < 0.5% of all breast neoplasms. Among the three histological subtypes:benign, borderline and malignant:the malignant variety is the most uncommon. Giant phyllodes tumours measure > 10 cm in their largest dimension. Overall prognosis for these lesions is poor, with high recurrence rates. Surgery with post-operative adjuvant chemoradiotherapy is the main treatment for malignant giant phyllodes tumours. We present a rare case of malignant giant phyllodes tumour of the left breast in a 23-year-old female patient with retrosternal extension and invasion of the pericardium.",
"gender": "Female"
},
{
"age": 23,
"case_id": "PMC6180860_02",
"case_text": "A 23-year-old female patient presented to the oncosurgery department with complaints of a large left breast mass for 3 years (Figure 1). The mass initially presented as a small lump, which gradually grew in size. During this time, she felt no pain or discomfort. In the past few months, the patient noticed rapid growth in the size of the lump along with discolouration of the breast skin.\nClinical examination revealed an enlarged breast completely replaced by a lobulated mass that measured approximately 21 x 12 x 13 cm. No enlarged axillary lymph nodes were noted. The contralateral right breast was normal in appearance as well as on palpation.\nInitial chest radiograph (Figure 2a) showed a multilobulated soft tissue density lesion involving the left breast. Bilateral lung fields and the bony thoracic cage appeared normal. On ultrasound (Figure 2b), the lesion appeared as a circumscribed, multilobulated, heteroechoic solid lesion, with internal vascularity on colour Doppler (Figure 2c). As the lesion was massive in size and could not be adequately assessed by radiography or ultrasound, the patient was referred for CT scan of the chest for further evaluation. Post-contrast CT scan of the chest (Figures 3 and 4) revealed a heterogeneously enhancing aggressive lesion measuring 21 x 15 x 13 cm with central areas of necrosis, with evidence of sternal erosion and invasion of the pericardium. The adjacent vessels, lungs and cardia appeared normal with no evidence of invasion. There was no evidence of lymphadenopathy. The patient underwent left mastectomy followed by adjuvant chemoradiotherapy. Histopathological evaluation of the excised specimen confirmed the diagnosis of malignant phyllodes tumour.",
"gender": "Female"
}
] |
PMC6180860
|
[
{
"age": 70,
"case_id": "PMC4769045_01",
"case_text": "The patient was a 70-year-old male who presented with a 6-month history of vomiting, epigastric pain and weight loss. A gastroscopy revealed a large submucosal lesion originating in the fundus of the stomach and the biopsies were inconclusive. CT study revealed a 12x10x9 cm partially calcified mass with heterogeneous contrast enhancement on the fundal region and greater curvature of the stomach (Figure 1). The patient underwent a total gastrectomy associated to a distal splenopancreatectomy and segmental transverse colectomy (Figure 2). The final pathologic diagnosis was collision tumor of gastric GIST and pancreatic adenocarcinoma (Figure 3, Figure 4).",
"gender": "Male"
}
] |
PMC4769045
|
[
{
"age": 55,
"case_id": "PMC9354553_01",
"case_text": "A 55-years-old gentleman presented with chronic progressive course of walking difficulty for 8 years and dysarthria for 3 years. He also complained of heaviness and stiffness of both lower limbs while walking. He was taking multiple stuttering in-place steps before starting, and was walking in broad base with hesitant steps with difficulties in turning. He used bizarre dance-like bilateral upper limb movements to compensate and steer forward (Video 1). The problem increased when he was given a mental task like counting backwards from 100. A graduate, he was born of non-consanguineous marriage of Indian parentage with normal birth and developmental history.\nHe scored 82 in Addenbrooke's Cognitive Examination and 15 in Frontal Assessment Battery. He showed mild attentional deficit and poor delayed recall in word list memory task, that improved with cues with preserved other cognitive domains. His examination revealed slurred speech, mild spasticity of four limbs, normal limb power with brisk deep tendon reflexes (DTRs). He could perform complicated coordinated motor activities by lower limbs while lying down like drawing numbers in the air or cycling in midair (Video 2). However, his gait problem did not improve with visual cues. His MRI (magnetic resonance imaging) of brain showed bilateral posterior predominant periventricular white matter hyperintensities in T2 and FLAIR sequences suggestive of leukodystrophy (Figure 1A-E and 1I-L). Investigations including complete blood count, blood biochemical parameters, serum lactate, creatinine phosphokinase, electrocardiogram and 2D echocardiogram were normal. Tests for arylsulphatase A, urinary metachromatic granules and very long chain fatty acids came negative. There was no family history, but on examination, his brother was found to have dysarthria with mild spasticity and brisk DTRs in lower limbs. His brain MRI also showed posterior predominant white matter hyperintensities (Figure 1 F-H). Clinical exome of the index case by next generation sequencing revealed likely compound heterozygous mutations of the AARS2 gene namely NM_020745.4 (AARS2):c.1874G > A (p.Arg625His) and NM_020745.4 (AARS2):c.179C > A (p.Pro60His) which were classified as being \"likely pathogenic\". Parental study could not be performed in this patient and thus there was no data regarding trans or cis position of the mutated alleles in the compound heterozygous state. In-silico prediction found both the variants to be damaging. No other variants in any gene causing leukodystrophy were found. He was put on coenzyme complex therapy and other supportive treatment, and is now under follow-up. His brother denied permission for genetic testing.",
"gender": "Male"
}
] |
PMC9354553
|
[
{
"age": null,
"case_id": "PMC4345035_01",
"case_text": "Capecitabine is originally indicated for the treatment of breast cancer and colorectal cancer as stated in the drug label. In this case study, we aimed to seek alternative indications for Capecitabine. We searched for Capecitabine with RxCUI \"194000\" from the CPN to identify novel indications. In total, there are 120 disease nodes that are at most 3 nodes away from Capecitabine. Of these 120 diseases, 12 possible novel indications including Hyperbilirubinemia, Mesothelioma, Bladder Neoplasm, etc. associated with Capecitabine are supported by published studies. The following example illustrates the identification process of the new indication, bladder neoplasm for Capecitabine.\nFrom the CPN 50 directly relevant nodes have been retrieved for Capecitabine including the gene CYP1A1, from which \"Urinary Bladder Neoplasms\" have been identified subsequently. A sub-network of Capecitabine visualized by Cytoscape in the CPN is shown at the right lower corner in Figure 1, where the edges in red indicate all associations with Capecitabine, and the green edges indicate DPYD and C18orf56 are linking to Capecitabine respectively. The zoomed out network is shown in Figure 3. The association between \"Urinary Bladder Neoplasms\" and \"Capecitabine\" could be inferred through multiple paths as shown in Figure 3. Among all paths between these two, the shortest path is Capecitabine-CYP1A1-Urinary Bladder Neoplasms, of which the association could be proved by literatures: (1) \"CYP1A1 rs1048943 A > G (Ile462Val) polymorphism is a potential prognostic marker for survival outcome after docetaxel plus capecitabine chemotherapy\"; (2) active CYP1A1 and CYP1B1 overexpression is revealed in bladder cancer; (3) the combination of Capecitabine and radiation therapy offers a promising treatment option for bladder cancer patients who are not candidates for surgery or cisplatin-based chemotherapy; (4) a patient with metastatic bladder cancer responded well to second-line capecitabine with a clinically meaningful progression-free survival. Through this validation chain, the inference that the breast and colorectal cancer drug, \"Capecitabine\" might be used for urinary bladder cancer could be made. Evidently urinary bladder cancer may be a novel indication of Capecitabine via the network-based analysis of the CPN.",
"gender": "Unknown"
}
] |
PMC4345035
|
[
{
"age": 76,
"case_id": "PMC9577112_01",
"case_text": "A 76-year-old woman reported a history of progressive sensorimotor disturbance in both lower limbs for the past 2 years. Initially, the patient's condition was misdiagnosed as \"lumbar disc herniation\" in the local hospital, and she received conservative treatment. However, her symptoms did not improve and became more serious. When referred to our hospital, she complained of inability to walk and bladder and bowel control loss. A neurological examination revealed a diminished sensation below the T7 level. The strength of both lower limb muscles was 1/5. Her neurological status was diagnosed as Nurick Grade 6. Magnetic resonance imaging (MRI) revealed multiple intradural extramedullary tumors at the T7-T11 level compressing the spinal cord (Figure 1A). Computed tomography (CT) scans showed five high-density masses of varying sizes in the spinal canal at the T7-T12 level, and the dural sac was significantly compressed (Figures 1B,C). Three large high-density masses (13.4 mm*8.4 mm, 21.7 mm*13.0 mm, and 14.9 mm*12.5 mm) were observed in the T7-T9 segment, located in the dorsal left rear spinal cord with clear boundaries and ossification signals (Figures 1D-F). The other two high-density masses (8.7 mm*5.3 mm and 11.1 mm*6.73 mm) of different sizes were found in the T10-T12 segment.\nThe patient underwent tumor resection through T7-T11 laminectomy. The tumors occupied >90% of the transverse diameter of the spinal canal and were entirely ossified. As the vertebral fenestration was too small, it was challenging to remove the tumors. Hence, the bilateral facet joints were removed to enlarge the window. To maintain the stability of the spine, we performed T7-T12 long-segment pedicle screw fixation and posterolateral bone graft fusion simultaneously. Bilateral facetectomy provides advantages over simple laminectomy or laminoplasty in terms of width of the operative corridor and long-term preservation of the spinal alignment. As the dura mater had severely adhered, a fine right-angled hook was used to dissect the neural tissue dorsally away from the neoplasms, which were then resected en bloc, together with parts of the dura mater and arachnoid. After a complete separation of multiple OSMs, the dura mater became normal and it was sutured. The drainage was routinely placed, and the wound was closed layer by layer.\nThe paraffin sections were stained with hematoxylin and eosin (H/E). A histopathological examination revealed a large number of psammoma bodies in the stroma with significant signs of ossification [World Health Organization (WHO) Grade I]. In addition, there were many mature bone tissues around the tumor cells, including trabecular bone, as well as bone marrow with hematopoiesis (Figures 2A-C). Immunohistochemical findings revealed EMA (+), Vim (+), P53 (-), S-100 (+), and Ki67 (approximately 5%) (Figures 3D-F).\nPostoperative neurological improvement was significant, and no complications were found. The patient was discharged 2 weeks after surgery. After the 2-year follow-up, she was able to walk without assistance. Her neurological status recovered to Nurick Grade 3. CT scans showed a total resection of the tumors, and there was no recurrence 2 years after surgery (Figures 3A-E).",
"gender": "Female"
}
] |
PMC9577112
|
[
{
"age": 4,
"case_id": "PMC8113859_01",
"case_text": "In 2015, a 4-year and 6-month-old boy was admitted to our hospital for recurrent lung infections and hematuria for more than 2 years. Physical examination on admission revealed visible tonsils; cervical, axillary, and inguinal lymphadenectasis; dry rales in his both lungs; no murmurs in the heart; abdominal softness, no hepatosplenomegaly; no positive signs on nervous system. He had a BCG vaccination at birth with no adverse effects. Epstein-Barr (EB) virus IgM and cytomegalovirus (CMV) IgM were detected. High titers of anti-neutrophil cytoplasmic antibody (ANCA) for PR3 were detected (see Table 1 ). Chest CT showed pulmonary nodules with cavity formation, bronchiectasis, and patchy infiltration. Bilateral maxillary and ethmoid sinusitis were also seen in paranasal sinuses CT ( Figures 1A, B ). Ultrasound suggested the enlargement of liver, spleen, and superficial lymph nodes. Urine routine revealed increased urine red blood cells. Renal biopsy pathology indicated slight glomerular lesions ( Figure 1C ). Lymph node biopsy only demonstrated reactive hyperplasia. Bronchoscopy revealed no obvious abnormalities. Lung biopsy suggested an uneven distribution of lesions, and infiltrations of lymphocytes around the bronchiole with hyperplasia of collagen fibers ( Figure 2 ). Bone marrow aspiration indicates hyperplasia of granulocytes.\nThe boy was diagnosed as GPA based on upper airway, lung, and kidney involvements, and positive ANCA (refer to EULAR/PRINTO/PRES criteria). He was treated with oral prednisone at the initial dose of 1 mg/kg/day, tapered to 0.2 mg/kg/day by month 6, and 0.15 mg/kg/day as maintenance therapy. At the same time, he was given monthly intravenous cyclophosphamide infusion at the dose of 500mg/m2 for 6 months, and then mycophenolate mofetil was started as maintenance therapy. His hematuria improved. However, he still experienced recurrent lung infections within 2 years of follow-ups, and repeated bronchoscopy showed mucosal nodules. This patient was suspected of having lymphoproliferative disease and accepted genetic testing with the consent of his mother (his father not available). A mutation E1021K (c.3061 G >A) in the PIK3CD gene was found in this boy, while his mother had no mutation. He was then diagnosed with APDS1 and received regular immunoglobulin (400 mg/kg/month) and rapamycin treatment with the improvements of lung infection and hematuria. Considering his pulmonary infections, he was treated with piperacillin and Tazobactam, and then received Trimethoprim/Sulfamethoxazole prophylaxis for 6 months.",
"gender": "Male"
},
{
"age": 7,
"case_id": "PMC8113859_02",
"case_text": "Another patient was a 7-year and 9-month-old girl who presented with recurrent lung infections and hematuria for more than 6 years. During the past 6 years, she suffered from recurrent sinusitis, lung infections, and hematuria. The girl had positive ANCA and diagnosed as GPA. Although she received prednisone, her clinical manifestation failed to improve. Therefore, she was admitted to our Department of Rheumatology & Immunology in 2018. Physical examination revealed visible tonsils and cervical lymphadenectasis, but no clinical features suggestive of autoimmune disease. She had mild developmental retardation. CT also showed pulmonary nodules with cavity formation, and patchy infiltration, and bilateral maxillary sinus and ethmoid sinusitis ( Table 1 , Figures 1D, E ). Abdominal ultrasound suggested hepatosplenomegaly and enlarged lymph nodes. Due to recurrent and refractory lung infections, she underwent bronchoscopy during hospitalization, showing mucosal nodule lymphoid hyperplasia in the entire airway ( Figures 1G-I ). Bone marrow and lymph node biopsies had no abnormal findings. Lung biopsy suggested inflammatory cells infiltration ( Figure 2 ) and absence of granulomatous lesions, and renal biopsy pathology indicated mild glomerular disease ( Figure 1F ).\nDue to mucosal nodules of the airway, the patient was suspected of lymphoproliferative disease, and accepted genetic testing with the consent of her parents. Whole exome sequencing showed that she had a de novo mutation E1021K (c.3061 G >A) in the PIK3CD gene, while none of her parents had this mutation. In the end, she was diagnosed as APDS1, and received regular immunoglobulin (400 mg/kg/month) with reluctance to use rapamycin by her parents. In view of her pulmonary infections, she was treated with Cefoperazone and Sulbactam, and then received Trimethoprim/Sulfamethoxazole prophylaxis for 6 months. At present, her lung infections significantly improved.\nImmunohistochemical staining of p110delta, CD3, and CD20 were performed in biopsy tissues of both patients taken previously ( Figure 2 ). Increased expression of p110delta was found in histological sections of the lung and lymph node compared with the control, indicating increased recruitments of p110delta expressing cells ( Figures 2B, C, E, F ). Notably, significantly increased numbers of inflammatory cells were observed around airways and in the lung parenchyma, especially the infiltrations of CD3+ T cells ( Figures 2H, I, K, L ). This study was approved by the Ethic Review Board of Children's Hospital, Zhejiang University School of Medicine (2019-IRB-105). Written informed consent was obtained from their legal guardians for the publication of any potentially identifiable images or data included in this article.",
"gender": "Female"
}
] |
PMC8113859
|
[
{
"age": 37,
"case_id": "PMC4065704_01",
"case_text": "A 37-year-old woman presented with a 3-month history of fullness and progressive hearing loss in the left ear. There was no tinnitus, otalgia, otorrhea, vertigo, or facial nerve paralysis. Otomicroscopy of the left ear showed the presence of a reddish, easily bleeding hypotympanic mass, extending to the medial third of the external auditory canal. Examination of the facial nerves, nasopharynx, oral cavity, larynx, and neck was normal. Neither the symptoms nor a family history of VHL disease was found in the patient. The pure-tone audiometry revealed a moderate, pantonal, conductive hearing loss in the left ear (Figure 1). Computed tomography (CT) demonstrated an irregular, hypodense, and expansile lytic lesion of the mastoid process of the left petrous bone extending to the middle ear, with a subtotal erosion of ossicular chain and the \"tegmen tympani.\" The mass did not appear to affect the semicircular canals, the canal of the facial nerve, and the internal auditory canal (Figure 2). Cerebral magnetic resonance (MR) confirmed the presence of a lesion of increased signal on T1-weighted sequences, enhanced in the medial portion of the middle ear and in the tubaric region (Figure 3). The patient underwent a canal wall-down tympanoplasty and complete removal of the tumor. The facial nerve was exposed to a tract of about 3 mm at the level of the second genu. The postoperative follow-up was uneventful. Histopathology was consistent with ELST. The tumor presented the architecture of a papillary adenocarcinoma of low histologic grade. There was no evidence of mitosis or necrosis (Figure 4). Immunohistochemical studies were positive for CK MNF116 (cytokeratin wide spectrum:types 5, 6, 8, 17, and 19) and chromogranin A (Figure 5), with a Ki67 not being significant. The tumor did not stain with GFAP (glial fibrillar acid protein), synaptophysin, S100, calponin, vimentin, and thyroglobulin. Genetic testing for the von Hippel-Lindau disease (mutation of chromosome 3p25/26) was negative. A postoperative MRI revealed no residual tumor. Radiological and clinical evaluations at 36-month follow-up demonstrated no evidence of recurrence and a pure-tone audiometry identified any worsening of hearing loss (Figure 6).",
"gender": "Female"
}
] |
PMC4065704
|
[
{
"age": 65,
"case_id": "PMC6477499_01",
"case_text": "A 65-year-old Caucasian male presented with painless horizontal diplopia on left gaze. His past history included coronary artery stents, hypercholesterolaemia, and he was an ex-smoker of 20 cigarettes/day. He denied intravenous drug use and having sex with men. His daily medications included amlodipine, valsartan, clopidogrel, and rosuvastatin. He had an ophthalmic history of left herpes simplex keratitis. Best corrected visual acuity was 6/9 (right) and 6/24 (left). The right cornea appeared normal; the left had stromal scarring without neovascularisation. Lenses, pupils, optic discs, and vitreoretinal examination were normal. He had left esotropia and left lateral rectus underactivity, with right gaze-evoked nystagmus. Hardy-Rand-Rittler colour plates tested all plates correct bilaterally. Automated visual field testing (Humphrey, Zeiss, Oberkochen, Germany) was full in both eyes. Full blood examination, CRP, ESR, fasting lipids, and renal function were normal. MRI of the brain showed minor bilateral pontine ischaemic changes. He was not tested for syphilis. He was diagnosed with microvascular left 6th nerve palsy. Diplopia resolved spontaneously over the next 3 months and his 6th nerve palsy remained detectable for 6 months before fully resolving.\nHe represented 6 months later with 8 weeks of painless \"smeared vision\" with yellow, red and orange colours seen vividly in both eyes. On further questioning, he reported previous treatment for gonorrhoea, presence of a primary chancre 12 months earlier, and having had sexual intercourse with a same-sex partner for 2 years. Visual acuities were 6/12 (right) and left 6/30 (left) (vision summarised in Table 1). Anterior segment examination was unchanged. Both pupils were dilated with no constriction in response to light, accommodative targets or 0.1% topical pilocarpine. Optic discs had developed mild temporal pallor (Fig. 1). Vitreoretinal examination remained normal. Motility testing was full. Automated field testing suggested a right superior defect (Fig. 1), although reliability indices were low. Optical coherence tomography scan of the retinal nerve fibre layer and ganglion cell layer demonstrated thinning in both eyes. MRI of the brain was unchanged. Serum treponemal antibodies and Treponema pallidum particle agglutination were reactive, with rapid plasma reagin reactive titre of 1,280. Further testing is summarised in Table 2. He did not have a lumbar puncture at this time. He was diagnosed with neurosyphilis and admitted to hospital. He reported allergy (rash) to penicillin and was treated by penicillin desensitisation followed by high-dose intravenous (IV) benzylpenicillin (1.8 g 4-hourly) for 16 days. He received 50 mg oral prednisolone for 3 days for Jarisch-Herxheimer reaction prophylaxis. Despite antibiotic treatment, serial examination showed the vision loss progressed to 6/60 in both eyes by June 2014 (Table 1).\nOn review in July 2014, 4 months after diagnosis and antibiotic treatment, visual loss had progressed further to 2/60 (right) and 3/60 (left), optic nerve pallor had increased, and a central scotoma had developed in both eyes. Lumbar puncture showed CSF weakly reactive to T. pallidum antibodies (EIA, fluorescent) and T. pallidum particle agglutination. Skin biopsy showed non-specific IgE, IgM and C3 immunofluorescence in the basement membrane and dermis. He was diagnosed with autoimmune optic neuropathy, re-admitted to hospital and treated with a second course of IV benzylpenicillin after repeat desensitisation, together with IV ceftriaxone 2 g daily given his earlier lack of response to penicillin, along with a 3-day course of IV methylprednisolone 1 g daily. He commenced immunosuppression and was discharged taking a tapering course of oral prednisolone, initially 75 mg daily, oral doxycycline 100 mg twice daily for 28 days and azathioprine 75 mg daily, and 1 month later given a 3-day course of IV immunoglobulin (Octagam 5% 45 g daily).\nWhen last reviewed, there had been no response to sustained immunosuppression. Visual acuity was 3/60 bilaterally and optic discs were atrophic. Pupils remained non-responsive to both light and accommodative targets. The patient withdrew from medical care and ceased all treatment.\nOur patient has CSF-positive neurosyphilis with bilateral optic neuropathy and tonic pupils. Although he presented with only 8 weeks of visual symptoms, it is possible that the seemingly typical microvascular 6th nerve palsy 1 year earlier was early neurosyphilis. He denied risk factors and was not tested for syphilis at the time. Notwithstanding the uncertain onset of infection, his optic nerve function was normal at presentation with cranial nerve palsy, and he was treated appropriately within 8 weeks of first optic neuropathy symptoms with two courses of IV penicillin, IV high-dose steroids, and subsequent immunosuppression, but suffered progressive visual loss in the right followed by left eye with optic atrophy.\nWe hypothesise his progressive visual loss was due to the development of autoimmune optic neuropathy. This is supported by the relentless course despite appropriate treatment confirmed on serological response, skin biopsy positive for immunoreactant deposition, the most consistent marker of autoimmune optic neuropathy, and the development of autoantibodies (cardiolipin IgG, anti-smooth muscle). Multiple reports have linked post-infectious immune dysregulation with the development of autoimmune disease targeting the nervous system and the optic nerve. Syphilis is well known to induce autoantibody production. Although not all autoantibodies are necessarily pathogenic, this supports our case for autoimmune optic neuropathy complicating our patient's syphilitic optic neuropathy.\nOphthalmologists play an important role in diagnosing ocular and neurosyphilis. A high index of suspicion is necessary. Patients with syphilitic optic neuropathy need to be warned that visual loss may develop despite optimum therapy. Further research is needed to understand the mechanisms of visual loss in patients with syphilis.\nThe authors have no ethical conflicts to disclose.",
"gender": "Male"
}
] |
PMC6477499
|
[
{
"age": 45,
"case_id": "PMC5492790_01",
"case_text": "A 45-year-old lady presented to the emergency room (ER) with severe neck pain radiating to the left shoulder and arm, torticollis, and dysphagia for about two days. A clinical examination revealed limited cervical movement in all directions with exacerbation of pain on extension of the head. The primary clinical diagnosis in ER was cervicobrachialgia. The laboratory investigations revealed a leukocyte count of 11.5 x 103/mm3 (normal range 3.80-9.80 x 103/mm3) and C-reactive Protein (CRP) value of 7.8 mg/dL (normal range 0-5.0 mg/dL). Computed tomography (CT) and magnetic resonance imaging (MRI) were done and showed prevertebral soft tissue swelling and calcifications anterior to C1 at the insertion of the longus colli especially affecting the left side (Figure 1). After radiological confirmation of the diagnosis, non-steroidal anti-inflammatory drugs (NSAIDs) and a soft cervical collar were prescribed. The patient showed complete remission of symptoms after five days.",
"gender": "Female"
},
{
"age": 50,
"case_id": "PMC5492790_02",
"case_text": "A 50-year-old man was referred to our hospital with severe occipital headache (VAS 9), odynophagia. The CRP was 38 mg/dL. The main differential diagnosis was a retropharyngeal abscess, so the patient was first admitted to the ENT department where a clinical examination revealed posterior pharyngeal edema. Antibiotics and anti-inflammatory drugs were prescribed. A contrast-enhanced CT was done and revealed the prevertebral calcifications. The neuroradiologist suggested the diagnosis of longus colli tendinitis that was confirmed with contrast-MRI. A soft cervical collar and analgesics were prescribed. Symptoms rapidly improved after three days that the patient could be discharged. The patient reported complete remission of symptoms after seven days.",
"gender": "Male"
},
{
"age": 63,
"case_id": "PMC5492790_03",
"case_text": "A 63-year-old lady was presented to the ER with acute neck pain and dysphagia. She was afebrile. Laboratory investigations showed elevated CRP (39.7 mg/dL). MRI with contrast was done and showed inflammatory changes and contrast enhancement at the insertion of longus colli without prevertebral effusion. CT revealed the calcifications and confirmed the diagnosis of LCT.",
"gender": "Female"
},
{
"age": 48,
"case_id": "PMC5492790_04",
"case_text": "A 48-year-old man referred to our center with severe left-sided neck pain and dysphagia. Severe limitation of movements in all directions was evident on examination. The leukocyte count and CRP were elevated (15.6 x 103/mm3 and 51.3 mg/dL consecutively). Contrast-MRI revealed prevertebral edema, prevertebral effusion, and bone marrow edema of the anterior arch of atlas at the insertion of the upper oblique fibers of the left longus colli muscle mimicking spondylitis. CT scan was done and revealed the prevertebral calcifications. Under NSAIDs the inflammatory parameters were decreasing. Soft cervical collar helped to alleviate discomfort. Remission of symptoms was complete after 10 days.",
"gender": "Male"
},
{
"age": 51,
"case_id": "PMC5492790_05",
"case_text": "A 51-year-old lady presented to the ER with neck pain and rigidity. She had normal body temperature and normal leukocyte count and CRP. CT and MRT revealed calcifications at C1/2 level, prevertebral effusion, and soft tissue edema extending to the level of C4 (Figure 2). The case was diagnosed as LCT and NSAIDs were prescribed. Symptoms completely improved after two weeks.\n Table 1 summarizes the epidemiological, clinical, laboratory, and diagnostic findings in the five cases from our institution.",
"gender": "Female"
}
] |
PMC5492790
|
[
{
"age": 28,
"case_id": "PMC5822820_01",
"case_text": "A 28-year-old man presented with a painless palpable mass in the right scrotum. Scrotal ultrasound revealed a normal testicle and multiple 3 to 7 mm hyperechoic lesions adjacent to the right testis (Figure 1(a)). Contrast-enhanced computed tomography (CT) revealed high-density paratesticular tumors (Figure 1(b)). The surface coil magnetic resonance imaging (MRI) with a 1.5 tesla scanner (GE Healthcare Signa HDxt 1.5T) revealed iso- and low-intensity paratesticular tumors on T1- (Figure 1(c)) and T2-weighted MR images (Figure 1(d)), respectively. Short TI inversion recovery MRI showed low-intensity paratesticular tumors (Figure 1(e)). Water MRI showed high-intensity tumors (Figures 1(f) and 1(g)). The levels of testicular tumor markers such as alpha-fetoprotein, beta-human chorionic gonadotropin, and lactate dehydrogenase were normal. We planned tumor biopsy combined with intraoperative rapid diagnosis. Scrotal incision was performed to explore the scrotum, and paratesticular white pedicle masses were observed (Figure 2(a)). Over 20 nodules were observed at the tunica vaginalis. The maximum size of nodule was approximately 15 mm. Frozen section assessment was performed, and intraoperative rapid diagnosis suggested a fibrous pseudotumor without malignancy. We excised the paratesticular white masses (Figure 2(b)) and successfully performed testicular-sparing surgery. Pathological findings revealed the proliferation of typical fibroblasts that were distributed in multidirectional bundles of dissociated collagen fibers (Figure 2(c)). Lymphocyte infiltration including immunoglobulin G4- (IgG4-) positive plasma cells was observed. Tissue IgG4 counts and IgG4/IgG ratios were 10 positive cells per high-power field on average and 10%, respectively. Ki-67 labeling index was 2%. Immunohistochemical staining was negative for D2-40 (mesothelioma, Figure 2(d)), calretinin (mesothelioma, Figure 2(e)), beta-catenin (desmoid-type fibromatosis, Figure 2(f)), and anaplastic lymphoma kinase (ALK) (inflammatory myofibroblastic tumor, Figure 2(g)). No recurrences have been noted after 12 months of follow-up.",
"gender": "Male"
}
] |
PMC5822820
|
[
{
"age": 45,
"case_id": "PMC4312440_01",
"case_text": "Male patient aged 45 years at the time of diagnosis.\nChronic fatigue and pain in both shoulders and the lower back.",
"gender": "Unknown"
},
{
"age": null,
"case_id": "PMC4312440_02",
"case_text": "The patient visited a local clinic due to headache, dizziness, malaise, fatigue, and pain in both shoulders and the lower back. Symptoms persisted for several days and did not ease with medication. The patient underwent a complete blood count test; his white blood cell count was elevated to 34,100/mm3. The vital signs of the patient were normal, and the patient was stable without any fever. The clinical impression was leukemia, and the patient was referred to the hemato-oncology department of a university hospital. After admission, he underwent a bone marrow biopsy and a cytology exam. The results are reported in Table 1. Based on the biopsy results, he was diagnosed with CML and was started on chemotherapy.",
"gender": "Male"
},
{
"age": null,
"case_id": "PMC4312440_03",
"case_text": "The patient had never smoked and rarely drank alcohol.",
"gender": "Unknown"
},
{
"age": null,
"case_id": "PMC4312440_04",
"case_text": "The patient did not have hypertension, diabetes, tuberculosis, viral hepatitis, or human immunodeficiency virus infection.\nThere was no family history of hemato-oncologic diseases.",
"gender": "Unknown"
},
{
"age": null,
"case_id": "PMC4312440_05",
"case_text": "The patient started his job as a diagnostic radiographer in November 1990 and had continued working until he was diagnosed with CML. His job history is summarized in Table 2.\nThe patient's main jobs involved obtaining simple radiographs, including chest and abdominal radiographs. He also performed special radiography such as gastrointestinal series radiography and measuring bone marrow density. The working environment and the equipment he used are shown in Figures 1 and 2. The one-time exposure amount of the relevant diagnostic tools are listed in Table 3.\nThe patient's work profile also included fixation and development of the exposed films. We investigated the chemicals used to fix and develop the film, but we found no known compound that could be considered to have initiated oncogenesis.\nRecords of the patient's personal exposure dose from 1997 to 2012, measured by the TLD, were available. This is the official record provided by the Korea Workers' Compensation and Welfare Service (Table 4).",
"gender": "Male"
},
{
"age": null,
"case_id": "PMC4312440_06",
"case_text": "The patient mentioned that he was very stressed specifically from 2002 to 2006 because several cases of radiography had to be performed and there was no assistant to help with the workload. With regards to the missing records from 1990 to 1996, the patient estimated that the accumulated radiation would be comparable to that of 2003 to 2005, or even higher. Conventionally, younger workers tend to take more jobs than senior workers. Furthermore, the working environment then was worse than the present working conditions, and past radiologic shield methods were not as effective.\nBased on these assumptions, the PC was calculated by applying both the highest value (17.48 mSv) and the mean value (6.02 mSv) of annual radiation for the period of 1997-2012 (Table 5). The PC was calculated by the Radiation Health Research Institute-Program for Estimating the Probability of Causation (RHRI-PEPC), under the consultation of the Korea Hydro and Nuclear Power Company. The results showed that the point estimation of PC, i.e., the 50th percentile, was 58.83% for the highest estimation, and 57.28%, using the assumed mean value for the missing records.",
"gender": "Male"
}
] |
PMC4312440
|
[
{
"age": 18,
"case_id": "PMC8361550_01",
"case_text": "An 18-year-old female with a past medical history of migraine headaches presented to the hospital with chief complaints of persistent nausea, vomiting, inability to tolerate oral feeds, and significant weight loss for the past 2 months. The patient reported that she vomited after every meal, and vomitus mainly consisted of undigested food particles without blood. The patient also had intermitted constipation; however, she had no diarrhea. She also observed substantial weight loss despite good appetite but was unable to quantify the weight loss. The patient did not take any medications for her migraine headaches and her last flare-up was about 1 year ago. She reported multiple outpatient visits for similar complaints in the last 2 months; however, on this visit with her primary care provider, she was referred to the hospital. On clinical evaluation, she had stable vital signs. Physical examination revealed dry mucous membranes and abdominal examination was positive for mild epigastric tenderness along with decreased bowel sounds. The patient was started on intravenous (IV) fluids. Laboratory investigations such as complete blood count and comprehensive metabolic panel were ordered, which revealed a low hemoglobin level of 10.2 g/dL, hematocrit 30.2%, serum sodium 132 mEq/L, and serum potassium 3.3 mEq/L. An abdominal X-ray did not reveal mechanical obstruction. Due to concerns for gastroparesis (GP) as the underlying etiology, a Gastric Emptying Study was ordered, which revealed markedly delayed gastric emptying time as the tracer was distributed in the stomach on initial views with activity not appearing in the duodenum until 45 minutes and emptying half time was not reached with 77% of initial gastric contents remaining at the end of the examination. Hence, a diagnosis of GP was established. The patient was started on metoclopramide, which led to improvement of her presenting symptoms, and she was eventually discharged home with recommendations to taper the doses of metoclopramide as needed.\nOne month after discharge, the patient presented to the hospital with similar complaints as her initial presentation despite metoclopramide therapy. Laboratory investigations were similar to initial hospitalization and revealed hemoglobin level of 10.7 g/dL, hematocrit 31.9%, serum sodium 133 mEq/L, and serum potassium 3.2 mEq/L. An abdominal X-ray was ordered, which revealed dilated bowel segments with high burden of stool in the colon without obvious mechanical obstruction. A diagnosis of severe GP and chronic intestinal pseudo-obstruction (CIPO) was established. Over the next month, the patient was given an extensive trial of numerous prokinetic agents such as mirtazapine, ondansetron, pyridostigmine, octreotide, and promethazine, but she failed to show clinical improvement. With failure of medical therapy, a nasojejunal feeding tube was placed for nutrition; however, the patient noted worsening nausea despite the slow feeding rate of 10 mL/h. Hence, after detailed discussions with the patient, a decision was made to start her on total parenteral nutrition (TPN) after which she was transferred to a tertiary center for higher level of care. At the tertiary care center, she was continued on TPN and underwent extensive evaluation. Laboratory investigations were within normal limits except mild elevation of the liver enzymes. Additionally, antinuclear antibody, extractable nuclear antigens panel, paraneoplastic antibody panel, and acetylcholine receptor binding antibodies were found to be negative, thereby ruling out an autoimmune etiology. A right upper quadrant ultrasound revealed the presence of gallbladder sludge and normal liver architecture. An esophagogastroduodenoscopy (EGD) and colonoscopy were found to be negative. A small bowel follow-through ruled out mechanical obstruction. Magnetic resonance enterography and computed tomography angiography of the abdomen were noted to be unremarkable. Furthermore, a deep rectal biopsy was performed, which was negative for amyloidosis. However, antroduodenal manometry, a diagnostic tool for GI motility disorders, showed paucity of contractile activity with very low amplitudes highly suggestive of a myopathic etiology. This was followed up with a laparoscopic full-thickness intestinal biopsy, which revealed decreased actin staining in the circular muscles of the muscularis propria of small intestine consistent with a diagnosis of HVM. During the course of the hospital stay, the patient developed recurrent bacteremia, the source of which was identified to be the central venous catheter used for TPN. She was treated with appropriate antibiotics, which led to resolution of the bacteremia. Eventually, she underwent isolated small intestine transplant and was started on mycophenolate 500 mg daily, everolimus 5 mg daily, and prednisone 10 mg daily. This led to eventual resolution of her presenting symptoms, and she was discharged home. The patient continues to be asymptomatic and follows up with Gastroenterology and Transplant Surgery regularly.",
"gender": "Female"
}
] |
PMC8361550
|
[
{
"age": 25,
"case_id": "PMC7160736_01",
"case_text": "A 25-year-old G2 P0010 Caucasian female with past medical history of super morbid obesity (BMI 55.2), depression, and multiple sclerosis presented to us with bilateral lower extremity weakness and right-sided flank pain. At the time of presentation, she was at 18 weeks' gestation.\nShe was diagnosed with multiple sclerosis at age 17 after she developed right optic neuritis. Over a 3-year period, she tried multiple modifying agents including interferon beta 1-b which was associated with ovarian cyst formation requiring surgery and interferon beta 1-a, which had intolerable side effects and glatimer acetate. While on glatimer acetate, she had 2 relapses in 6 months. She was eventually transitioned to fingolimod with a single relapse shortly after initiation of therapy and treated with a 5-day course of solumedrol. Fingolimod was used successfully for 5 years and was discontinued 4 weeks prior to conception. Her pregnancy was complicated by a threatened abortion and persistent vaginal bleeding. She was placed on bed rest. During bed rest, she developed fever, flank pain, and severe paraparesis requiring hospitalization. She was diagnosed with an acute MS flare in the setting of pyelonephritis.\nAntibiotics and intravenous methylprednisolone 1,000 mg daily were initiated. A noncontrast MRI of the brain and cervical spine revealed a new extensive demyelinating lesion from C1 to C4. After the completion of 6 days of intravenous (IV) methylprednisolone, her lower extremity function had moderately improved, and she was able to ambulate with a walker and was discharged to an acute inpatient rehabilitation center.\nThree weeks later, she re-presented to the hospital with right-sided flank pain, generalized weakness resulting in a fall, and a tingling sensation in her extremities. Given the early recurrence, neurology was consulted. In the neurological exam, mental state was normal, pupils were normal symmetrical, and reactive to light. There was no facial asymmetry and the other cranial nerves were normal. Muscle tone was increased in her left upper extremity and bilateral lower extremities. In the motor exam, there was an asymmetrical moderate/severe tetraparesis mainly in the lower limbs and more pronounced distally. There was generalized hyperreflexia with bilateral clonus and bilateral Babinski. Sensation was impaired with decreased sensation to light touch, pinprick, and vibration without a clear sensory level.\nUrinalysis was consistent with a urinary tract infection and a urine culture grew out pan-sensitive Escherichia coli. A new MRI of the head (Figure 1) showed progression T2 hyperintense signal abnormality in the craniocervical cord. To exclude other differentials, her vitamin B12 and ACE levels were checked and were within normal limits. To rule out a possible diagnosis of neuromyelitis optica, an aquaporin 4 AQR4 antibody was tested and was negative.\nThe patient was started on antibiotics for suspected pyelonephritis, which was eventually changed to oral amoxicillin after urine culture sensitivities resulted.\nThe patient was started on IV methylprednisolone 250 mg every 6 hours. After five days of steroid treatment, she showed minimal motor improvement. At this time, rescue plasmapheresis (TPE) was initiated. Five treatments of TPE were performed every other day, alternating treatment days with IV methylprednisolone. The patient tolerated her therapy well and had progressive improvement in her neurologic symptoms with near complete resolution of her tetraparesis and mild residual sensory loss in her left arm. She was discharged to the acute rehabilitation service.\nFor the reminder of her pregnancy, she was treated with methylprednisolone 1000 mg as a single infusion every 3 weeks. She presented to the hospital at 36 weeks' gestation with contractions, vaginal spotting, hypertension, headache, and lower extremity edema. She was taken to the operating room for a cesarean section due to concerns of severe pre-eclampsia and preterm labor. She delivered a 2495 g male with APGARs of 8 and 9. After delivery, fingolimod was reinitiated in the outpatient setting.",
"gender": "Female"
}
] |
PMC7160736
|
[
{
"age": 4,
"case_id": "PMC6907107_01",
"case_text": "We found that the number of quadrants visualized positively correlated with age, confirming that younger patients are more difficult to image. Younger patients may be less cooperative. Positioning in the chin rest and fixating on a target can be challenging. Most quadrants could be captured by obtaining serial images with positive encouragement and assistance from the parents. Several patients aged 3-4 years old were included in our study to demonstrate the feasibility of acquiring high quality images at an early age. We feel that the child friendly protocol developed in our Medical Photography department at UCLA increases the success rate of pediatric retinal imaging. Interestingly, 2 patients with nystagmus were successfully imaged in our study. Our findings corroborate those of previous case reports suggesting ultra-wide field imaging of patients with nystagmus is possible due to the rapid (0.25 s) image acquisition time.\nWe also found more quadrants of the retina were visualized during the later phases of UWF-FA.\nChildren often require consolation following a needle stick for the fluorescein dye resulting in an increased time to image capture and difficulty in capturing choroidal filling. In addition, the delay in positioning the patient in the chin rest results in increased artifacts in the early phases. If the early phase of angiography is of interest, intravenous access can be acquired prior to injecting fluorescein which can eliminate the transition time. In addition, Ali et al. described using oral fluorescein as an alternative to intravenous dye to obtain UWF-FA in children.\nUWF-FAF was useful in capturing abnormal autofluorescence patterns in the macula and the periphery. Increased or attenuated autofluorescence patterns involved the periphery in 23 of 24 (96%) patients highlighting the usefulness of capturing the peripheral retina with UWF imaging. UWF-FAF has been described in case reports previously in Stargardt disease, pigmented paravenous chorioretinal atrophy, and long-chain 3-hydroxyacyl-CoA dehydrogenase retinal dystrophy. The peripheral extent of lesions and autofluorescence patterns may be useful to diagnose heredodegenerative disorders and monitor disease activity, particularly in inflammatory conditions.\nLastly, in our series, the indications for obtaining imaging were quite varied as seen in Table 1 which reflects the heterogenous nature of pediatric retinal disease. In addition, in children who reported floaters or visual disturbances with a normal eye exam, UWF imaging was useful to confirm and document a normal funduscopic examination. Several studies have demonstrated that UWF is useful as a screening modality for diabetic retinopathy with a sensitivity of 94% and specificity of 100% between UWF imaging and clinical examination. The use of UWF imaging as a screening modality can be applied to the pediatric retinal population as well.\nSimilarly, UWF-FA was particularly useful to confirm lack of activity or guide targeted panretinal photocoagulation in retinal vascular diseases. Moreover determining if a child who was previously treated requires additional treatment can be challenging. A negative UWF-FA, meaning one without significant ischemia or leakage, can guide the decision to observe with serial examinations and photographs and eliminate the need for an exam under anesthesia as shown in Fig. 4. On the contrary, a UWF-FA with active leakage or neovascularization as in a patient with proliferative diabetic retinopathy or Coats disease may indicate the need for additional panretinal photocoagulation (Fig. 5).\nThis study is limited by its retrospective nature. Another limitation of UWF-FA is that early vascular filling may not be imaged due to transition time from injection to photography. In addition, the periphery may be obscured by lash or nose artifacts. However, a strength of our study is the relatively large number of subjects included and we overcame challenges in positioning with coaching and parent involvement.\nFuture prospective studies can be considered to evaluate the time it takes to image subjects by age and compare UWF imaging with standard non-wide field cameras in the pediatric population. In addition, cost/benefit analysis of population screening in children using UWF technology can be considered.",
"gender": "Unknown"
}
] |
PMC6907107
|
[
{
"age": 34,
"case_id": "PMC6159306_01",
"case_text": "A 34-year-old Caucasian female, who had originally undergone an uneventful laparoscopic adjustable gastric band 4 years ago, presented to the bariatric surgery clinic with inability to tolerate solids. A work-up revealed that the laparoscopic band remained in good position but the patient had oesophagitis and gastritis, causing swelling of the mucosa at the band site. The fluid was removed from the reservoir, and the patient was treated conservatively with anti-reflux medication and a full liquid diet. After 2 weeks of treatment the patient's symptoms improved. After careful consideration, she wished to undergo revisional surgery converting the laparoscopic adjustable gastric band to a laparoscopic vertical sleeve gastrectomy. The patient moved through the appropriate multidisciplinary team approach and was found to be an appropriate candidate for surgery. She underwent laparoscopic removal of the adjustable gastric band and conversion to a laparoscopic vertical sleeve gastrectomy without complications. Her post-operative course was uncomplicated and she was discharged on post-operative day 3.\nOn post-operative day 12, the patient was readmitted to an outside tertiary care hospital for lightheadedness and shortness of breath and was found to have leukocytosis, with white blood cell count of 18,000 cells mul-1. The work-up included a CT scan with intravenous contrast of the chest, abdomen and pelvis, and the patient was diagnosed with a pulmonary embolism. The patient was immediately transferred to our centre for definitive care. When the patient arrived at our centre, the CT films from the outside hospital were reviewed by our radiologists and there was concern that there was air and a faint suggestion of oral contrast outside of the suture line (Figure 1). Given this finding, an UGI evaluation was ordered. During the early phase, no leak was observed, owing, in part, to the slow passage of 30 ml oral non-ionic contrast (Figure 2a). Some residual contrast from the outside hospital CT was present in the transverse and descending colon. Only after delayed imaging and with administration of additional non-ionic contrast for a total of about 65 ml (approximately 2 h after the start of the fluoroscopic examination) was there a faint suggestion of extravasated contrast, best seen below the left hemidiaphragm (Figure 2b). Follow-up CT scan with oral contrast confirmed the obvious leak (Figure 3).\nThe patient was treated definitively with endoscopic stent placement and clipping using an Ovesco clip (Ovesco Endoscopy AG, Tubingen, Germany) to close the leak. After an extended hospital course, she was discharged and is presently doing well.",
"gender": "Female"
}
] |
PMC6159306
|
[
{
"age": 76,
"case_id": "PMC6465717_01",
"case_text": "A 76-year-old woman had a history of left NECB, which was classified as pT2N1M0 stage IIB according to the Union for International Cancer Control (UICC) tumor node metastasis (TNM) classification. The patient was admitted to our hospital with complaints of a mass in the right breast without axial lymph node swelling on computed tomography (CT) (Fig. 1a). No associated pain, nipplagnete discharge, skin change, or palpable lymphadenopathy was noted. Contrast-enhanced mic resonance imaging (MRI) showed a mass with early arterial enhancement and gradual washout measuring 9.3 x 5.8 x 10.7 mm (Fig. 1b). Right breast mastectomy and axillary lymph node dissection were performed. The final pathologic diagnosis was NECB with small polygonal cells having a small amount of cytoplasm, high nuclear-cytoplasmic ratio, and finely granular chromatin (Fig. 2). According to the UICC TNM classification, it was classified as pT1N0M0 stage IA. A diagnosis of non-intramammary metastasis was made based on the results of immunostaining: chromogranin A (-), synaptophysin (+), Leu7 (-), CD56 (-) in the left NECB, and chromogranin A (-), synaptophysin (-), Leu7 (+), CD56 (-) in the right NECB. Six months after the operation, the patient initially underwent HD owing to unexplained chronic renal failure and continued the treatment as an outpatient. Forty months after a right breast mastectomy, CT revealed anterior mediastinal lymph node recurrence (Fig. 3a). Hence, we considered the recurrence of NECB and decided to initiate chemotherapy to prevent further recurrence. Based on the past literature on the chemotherapy dosage for patients on HD, a chemotherapy regimen with six cycles of FEC 100 - consisting of fluorouracil (5-FU, 500 mg/m2), epirubicin (EPI, 70 mg/m2), and cyclophosphamide (CPA, 350 mg/m2) - and three cycles of docetaxel (DTX, 60 mg/m2) was initiated (Table 1). After the third course of DTX treatment, grade 3 neutropenia was observed; hence, the chemotherapy was discontinued. CT was performed after the chemotherapy and anterior mediastinal lymph node recurrence was not detected (Fig. 3b). The patient responded well to the chemotherapy. Forty-two months after the chemotherapy, no tumor recurrence was detected on CT.",
"gender": "Female"
}
] |
PMC6465717
|
[
{
"age": 85,
"case_id": "PMC8084685_01",
"case_text": "An 85-year-old man with pancytopenia was diagnosed with MDS with multilineage dysplasia (MDS-MLD) based on bone marrow aspiration (BMA), which revealed 2.6% myeloblasts with trilineage dysplasia and normal karyotype. Based on these findings, the case was categorized as intermediate-1 or low risk according to the International Prognostic Scoring System (IPSS) or Revised IPSS (IPSS-R), respectively. At this point, the patient had been treated with vitamin K2 (menatetrenone) and active vitamin D3 (calcitriol) because combination therapy of these two drugs was reported to be effective against low-risk MDS. At 87 years of age, the patient undertook BMA again because his pancytopenia had progressed, and he was diagnosed with MDS with excess blasts-2 (MDS-EB-2) based on the BMA findings, which revealed 11% myeloblasts and multilineage dysplastic changes of bone marrow cells (Figures 1(a)-1(d)), with a normal karyotype. The disease status was categorized as intermediate-2 risk according to the IPSS and high risk according to the IPSS-R; thus, AZA treatment was initiated on hospitalization at the standard dose of 75 mg/m2/day, subcutaneously, for 7 days every month. The patient achieved a hematological improvement (HI) with manageable adverse events (AEs), including constipation and general malaise after the first cycle of AZA. The second cycle was therefore administered in an outpatient setting. However, the treatment was discontinued due to septic shock after the second cycle of AZA. The patient became dependent on red blood cell (RBC) transfusions due to a clinical progression of MDS because one year after the discontinuation of AZA (at 88 years of age), we did not perform any histological examinations, such as BMA. Therefore, additional 3 cycles of AZA were administered in an outpatient setting with a reduced dose of 37.5 mg/m2 (50% dose reduction) daily. The dose of AZA was decided according to the prescribing information for AZA based on the nadir absolute neutrophil count <0.5 x 109/L in the preceding (second) cycle. Treatment with AZA was discontinued again because the patient refused to continue the treatment due to the AEs, which included constipation and general malaise, as well as the inconvenience of going to the hospital.\nAt eight months after the second discontinuation of AZA (at 89 years of age), a painful cutaneous tumor, the top of which showed yellow-colored necrosis (Figure 2(a)), developed at the left groin lesion. Laboratory tests revealed the following: white blood cell count, 2,900/muL, with 63.6% neutrophils, 32.6% lymphocytes, 3.5% monocytes, 0.3% eosinophils, and no blast cells; hemoglobin, 6.6 g/dL; platelet count, 8.7 x 104/muL; and C-reactive protein, 0.57 mg/dL. No treatments, including oral and topical antibiotics, topical tacrolimus hydrate, and analgesics, had any effect on the tumor. A biopsy of the tumor was performed one month after its development. Histological examination revealed the proliferation of tumor cells with a high nuclear/cytoplasmic ratio (Figure 3(a)). Immunohistochemically, the neoplastic cells were positive for myeloperoxidase (Figure 3(b)), partially positive for cluster of differentiation (CD) 68 (Figure 3(c)) and CD33, but negative for CD3, CD4 (Figure 3(d)), CD20, CD34, CD56, CD117, and CD123 (Figure 3(e)). A diagnosis of MDS-associated MS was made. One month after the development of the first cutaneous lesion, another cutaneous tumor appeared on the left cheek (Figure 2(b)). BMA revealed a hypercellular marrow with 25% myeloblasts, which were positive for CD13, CD33, CD34, and HLA-DR; a G-band analysis revealed a normal karyotype. A diagnosis of AML secondary to MDS was made.\nConsidering the patient's age, clinical conditions, and the previously experienced AEs, treatment with AZA was started again at a dose of 37.5 mg/m2/day, subcutaneously, for 7 days every 4-6 weeks (in total, this was the 6th cycle of AZA treatment) during short-term hospitalization, which consisted of 9 days of inpatient treatment per cycle, in order to manage the acute-phase AEs caused by AZA. The cutaneous MS lesion located on the left groin (Figures 4(a)-4(c)) and that on the left cheek (Figures 4(d)-4(f)) promptly disappeared after the 6th and 7th cycles of AZA treatment. Although myeloblasts had appeared in peripheral blood after several cycles of retreatment with AZA, the treatment was continued because of persistence of the response on MS, and the pain caused by his lesions remained relieved, with tolerable AEs, by AZA. The patient had received 16 cycles (over a 22-month period) of AZA treatment with the same dose on repeated short-term hospitalization until he died of progression of AML. He eventually received 21 cycles of AZA treatment in total. No exacerbation of cutaneous MS had been confirmed during AZA treatment.",
"gender": "Male"
}
] |
PMC8084685
|
[
{
"age": 66,
"case_id": "PMC9846588_01",
"case_text": "A 66-year-old postmenopausal lady, presented with palpable, bilateral neck lymphadenopathy and difficulty swallowing. She also had left leg lymphoedema and complained of having poor appetite, fatigue, and lost 4 kg within 4 weeks. Patient denied having fever and night sweats. All these difficulties lasted approximately 1 month. Complete blood count (CBC) showed mild anaemia while all other laboratory findings were within normal limits. Also, HBV, HCV and HIV serology were negative. Colour doppler of lower extremities showed no signs of deep vein thrombosis and cardiac ECHO showed ejection fraction of 65%. Abdominal ultrasound showed para-aortic, bilateral pelvic and inguinal lymphadenopathy.\nAn excisional biopsy of enlarged axillary and cervical lymph node was performed. The cervical lymph node measured 1.8 x 1 x 0.7 cm and axillary node measured 3.6 x 2.6 x 2 cm. Nodes had firm consistency with no signs of necrosis or haemorrhage. Histological examination of lymph nodes showed effaced architecture, due to infiltration of polymorphic tumour lymphoid cells. The interfollicular area of lymph node was infiltrated with medium to large sized lymphocytes, having blastoid morphology indicative of centroblasts and immunoblasts and intermingled with plasmablast-like cells. Also, there were scattered large bi-nucleated cells similar to Reed-Sternberg cells. In between there were many eosinophils, histiocytes and plasma cells. Furthermore, within interfollicular areas, many mitoses and apoptosis were found. Four-micrometer sections from paraffin-embedded blocks were stained with each antibody listed below, using the streptavidin-biotin complex method. By immunohistochemistry, large atypical lymphoid cells were CD1a-, CD2-, CD3-, CD4-/+, CD5-, CD8-, CD20-, CD79a+, PAX-5-, CD38+, CD138-, CD30-/+, CD56-, MUM1+, PD-1-/+, Bcl-2-, ALK-, c-myc-, TdT-, CD45+, Bcl-6-, CD10- and HHV-8-. The Epstein-Barr encoding region (EBER) in situ hybridisation was negative (Figure 1). Kappa and lambda light chain in situ hybridisation did not show restriction. CD68 staining showed lot of histiocytes and Ki-67 proliferation index was high, approximately 65% (Figure 1).\nDue to the unusual morphology, as well as the immunophenotype of large, polymorphic cells, with blast and plasmablast-like appearance (CD20-/PAX-5-/CD79a+/CD38+/MUM-1+/CD4-/+) a multiplex polymerase chain reaction (PCR) analyses of B-cell and T-cell receptor rearrangement were performed using BIOMED-2 protocol. Briefly, BIOMED-2 multiplex PCR reactions using fluorescently labelled oligonucleotide primers were performed in triplicates with 50 ng and 200 ng of DNA per 50 microL reaction. Following PCR amplification, the PCR products were resolved using capillary electrophoresis on the SeqStudio (Applied Biosystems, USA) genetic analyser. GeneMapper software (Applied Biosystems, USA) was then used to analyse PCR products by peak height and size determination. The clonality analysis of IgH gene in FR2 and FR3 regions showed polyclonal distribution of PCR products (gaussian distribution of multiple peaks representing multiple PCR products) while the IgKappa gene clonality analysis showed only one prominent peak (monoclonal result consisting of one type of PCR product) (Figure 2). However, the T cell receptor analysis of TCR gamma region showed bi-clonal and TCR beta region monoclonal distribution of PCR products (Figure 3).\nConsidering histological, immunohistochemical and clonality analysis results our final diagnosis was primary nodal CD20 and PAX-5 negative DLBCL with dual IgK and TCR rearrangement. The whole-body computer tomography (CT) scan showed generalised lymphadenopathy and bone marrow biopsy showed no evidence of infiltration. Thus, a stage IIIB of disease was confirmed. Considering, poor prognosis of primary CD20 negative DLBCL, patient was treated with 6 cycles of the R-DA-EPOCH (dose adjusted rituximab, etoposide prednisolone, vincristine, cyclophosphamide, doxorubicin) chemotherapy protocol. The subsequent follow up laboratory tests as well as positron emission tomography and computed tomography scans (PET-CT) showed no evidence of lymphoproliferative disease 4 years after initial diagnosis. The collateral finding at the last control PET-CT scan was diffuse thickening of the large colon at sigmoid region. A colon surgery was performed, and histological examination showed colon adenocarcinoma (pT2, pN0). Other than that, patient did not have any health-related difficulties.",
"gender": "Female"
}
] |
PMC9846588
|
[
{
"age": 74,
"case_id": "PMC9053256_01",
"case_text": "FNH is rarely associated with HCC, however, the risk of malignant transformation from FNH to HCC has been already suggested. In this study, we describe a 74-year-old female patient with an FNH and a concomitant HCC nodule in a non-cirrhotic liver. The nodule consisted of two HCC components with distinct histopathological features. We demonstrated, using whole-exome sequencing (WES), that the FNH and the HCC share a common phylogenetic origin.",
"gender": "Female"
}
] |
PMC9053256
|
[
{
"age": 39,
"case_id": "PMC9829981_01",
"case_text": "A 39-year-old female premenopausal, P4 +0, presented to the breast surgery clinic with right breast swelling for ten years. The swelling started gradually following the excision of a right axillary lump. The mass was diagnosed as a right axillary CH of about 2cm x 1cm in dimensions. Just before her presentation, the swelling became big enough to disturb her daily activities. She had no family history of breast cancer. There were no other swellings elsewhere in her body. She was not a smoker or alcoholic, and there was no previous surgery or chronic illnesses. Examination revealed a swollen right breast with \"peau d' orange\" and erythema around the right nipple-areola complex (NAC). There was asymmetry in the shape of the right breast compared to the left and right breast ptosis. The skin was thickened and red but no hotness or tenderness. No masses were felt in the right breast. The right NAC appeared normal. Apart from the linear scar of the previous CH excision in the right axilla, the axilla was normal. Left breast and axilla examination revealed no obvious or palpable abnormalities (Figure 1). Ultrasound examination of the breast and axilla revealed mild skin thickening. The breast parenchyma was dense and showed an anechoic tubular and round structure. The right breast showed a loculated cystic area with internal septations. It measured 3.4cm x 1.2cm x 5.1cm and multiple smaller cyst (Figure 2A). The mammogram showed marked skin thickening with edema (Figure 2B). \nWe attempted needle aspiration away from the cysts, and the fluid was easily aspirated from the edematous breast tissues. The fluid was watery and clear yellowish. The laboratory result of the fluid was lymphatic fluid. Aspiration trials were repeated twice with almost a complete resolution of the edema, but there was a recurrence within two weeks in every aspiration attempt. Subsequently, the patient consented to a shunt catheter placement between the edematous breast and the peritoneal cavity, a relatively new technique for breast edema secondary to CH. There was a partial resolution of the breast edema after the shunt surgery. The patient was followed up for five years. The last ultrasound and mammogram showed recurrence of cysts of the same axilla, and new cysts appeared in the breast (Figure 3A and B).",
"gender": "Female"
}
] |
PMC9829981
|
[
{
"age": 2,
"case_id": "PMC5295181_01",
"case_text": "A 21/2 year-old girl presented with an asymptomatic painless mass in the right upper abdomen. On physical examination, a 7x6 cm, nontender, firm and well-defined mass with smooth surface was noted in the right hypochondrium extending to the epigastric and umbilical regions as well as to the right iliac fossa. Family history of paternal twinning was present. On imaging, a frontal radiograph of the abdomen showed multiple dense radio-opacities in the right upper quadrant of the abdomen resembling well-formed limb bones and spine (Figures 1, 2). On abdominal ultrasound, there was evidence of a heterogeneous right suprarenal mass with coarse calcifications and solid areas. On contrast-enhanced computed tomography of the abdomen (Figures 3, 4) with a 3D-volume-rendering technique (Figure 5), a heterogenous, well-circumscribed soft tissue mass was noted in the right anterior pararenal space in a suprarenal location. It showed multiple bony densities resembling a spine, limb bones, ribs and pelvic bones. These bony densities were surrounded by soft tissue and fat. No obvious contrast enhancement in the soft tissues was noted. Radiological diagnosis of FIF was considered and the child was referred to a surgical ward.\nOn laparotomy, a right upper quadrant retroperitoneal mass (Figure 6A),~10x12 cm in size, covered with a sac was noted displacing the liver towards the left side and the right kidney anteriorly, stretching the right renal vessels. Venous drainage from the mass was enabled by a direct tributary of the inferior vena cava (IVC). On opening the sac (Figure 6B, 6C), 50 ml of vernix caseosa, along with a malformed fetus with an anencephalic head, spine, upper and lower limb buds with nails and partially differentiated digits were noted.\nOn the histopathological examination, the gross specimen showed a partially developed fetus with partial differentiation of the four limbs, skull and spine with palpable vertebrae, bones, scapula and ribs. Microscopic sections showed mature derivatives of the ectoderm, mesoderm and endoderm. No immature components were identified. There was no evidence of somatic or germ cell malignancy. A final diagnosis of fetiform teratoma was made. The child is on a regular follow-up and at 11/2 years following surgery there is no evidence of recurrence.",
"gender": "Female"
}
] |
PMC5295181
|
[
{
"age": 18,
"case_id": "PMC10098112_01",
"case_text": "The proband, a girl, is the only child of healthy, non-consanguineous parents. She was first referred to our Unit of Clinical Pediatrics at the age of 18 months for a diagnostic workup regarding her microcephaly. She was born at 39 weeks of gestation by caesarean section; the pregnancy was characterized by an ultrasonography diagnosis of microcephaly, reduced gyral pattern, and agenesis of the corpus callosum at gestational age 25 weeks. Serological screening for congenital infections (i.e., Cytomegalovirus, Toxoplasma gondii, Varicella-Zoster Virus, and Hepatitis C Virus) during pregnancy and at birth (in the mother and her daughter) was negative, as was the proband neonatal extensive screening for inborn errors of metabolism. Her birth weight was 2.6 kg, height was 47 cm, and head circumference was 32 cm (all below the 3rd percentile). Neonatal history was negative, and she was not breast-fed by the mother.\nAt our first diagnostic workup, at age 18 months, her weight was 8.4 kg (<3rd percentile), height was 74 cm (<3rd percentile), and head circumference was 38.5 cm (<3rd percentile, -5.6 standard deviations). Three small hyperpigmented maculae (1-cm diameter each) were present on her abdomen. The mother reported irritability and sleep disorders (insomnia). She underwent a new heart examination by means of ECG and echocardiography, abdominal ultrasound, and full ophthalmological examination, all of which were normal. Her eye-to-eye and social interaction with parents and other people was within normal limits, but she was not able to walk alone and spoke only a few words. Brain MRI and additional laboratory and instrumental investigations were planned but the family was temporarily lost to follow-up due to the Covid-19 pandemic.",
"gender": "Female"
},
{
"age": 3,
"case_id": "PMC10098112_02",
"case_text": "At the age of 3.5 years, the family again referred the child for completion of her diagnostic work-up. At that stage, brain MRI showed microcephaly with a small brain, simplified parieto-temporal gyral pattern, hypoplasia of the corpus callosum, with a residual draft of the genu, and enlargement and flattening of the ventricles, with colpocephaly and ectasia of the temporal horns (Figure 1). At the age of 4 years, her general conditions were good. Her weight and height were 12.1 kg and 89 cm, respectively (<3rd percentile), head circumference was 40 cm (<3rd percentile, -5.6 standard deviations), the girl was able to walk, did not present any seizures, and showed moderate intellectual disability [IQ by means of WPPSI-III = 67; verbal comprehension index = 61; visual spatial index = 72; fluid reasoning index = 63; working memory index = 70; processing speed index = 69]. She was assisted by a support teacher at school and was under speech-language therapy twice a week.",
"gender": "Female"
},
{
"age": null,
"case_id": "PMC10098112_03",
"case_text": "The girl and her parents underwent next-generation sequencing (NGS) testing with a panel of 161 genes related to brain malformations. A novel variant (c.611G > A), in one copy of the TSC1 gene, was found in the child, and not in her parents (interpreted as a de novo variant). An in-silico analysis was performed using VarCards, ProAffiMuSeq, and Mutation Taster tools (see the following sections). Over the following months, the variant was confirmed by Sanger sequencing of the gene; the girl and her parents were also submitted to a further whole exome sequencing analysis, which confirmed the results of the NGS panel and failed to find additional variants in other genes. The TSC1 variant was hypothesized to cause a gain-of-function effect on hamartin, and consequent hyperactivation of its downstream effectors.",
"gender": "Female"
}
] |
PMC10098112
|
[
{
"age": 26,
"case_id": "PMC3323263_01",
"case_text": "The index patient, a 26-year-old woman, was admitted to the infectious disease ward of a university hospital with a temperature of 40 C and myalgias 3 days after she returned from a 3-week trip to Cambodia and Thailand. Dengue virus infection was subsequently diagnosed, and mild hepatitis and a rash developed. She was discharged in good condition after the fever subsided. On the day of admission of the index patient (day 0i), a nurse sustained a needlestick injury with a hollow needle that had been used for drawing blood from the index patient. The needlestick resulted in a bleeding puncture wound that was immediately treated with an antiseptic. The index patient did not report any high-risk activity for HIV or hepatitis B virus, and the nurse had been immunized against hepatitis B virus. Therefore, no specific postexposure prophylaxis was performed. The nurse had previously been in good health and had not traveled outside Germany in the preceding 12 months.\nFour days after the needlestick, headache, myalgias, and arthralgias developed in the healthcare worker, for which she took ibuprofen. Seven days later, when she was experiencing an intense headache and noticed a macular rash on her trunk, she sought treatment from a local doctor (day 0n). Physical examination showed bilateral cervical lymphadenopathy. On day 2n, she visited our service, where dengue virus infection was diagnosed by using a Light Cycler (Roche Diagnostics, Mannheim, Germany) polymerase chain reaction (PCR) method. Her symptoms lessened gradually over the course of 4 weeks, and she was on sick leave for 5 weeks. The time frame of the respective clinical presentation and the virologic results of the index patient and the nurse are shown in the Figure; laboratory data are presented in the Table.\nSerologic studies were performed with the PanBio dengue immunoglobulin (Ig) M capture enzyme-linked immunosorbent assay (ELISA) and PanBio dengue indirect IgG ELISA (PanBio Ltd., Brisbane, Australia); arbitrary units relative to a simultaneously measured calibrator >11 were considered positive. For detecting virus RNA, RNA was prepared from 140 microL of serum by using the QIAamp Viral RNA Mini Kit (Qiagen, Hilden, Germany), according to the manufacturer's instructions. To detect specific dengue virus RNA, we adapted a TaqMan-reverse transcription (RT)-PCR to detect any of the four serotypes by using the following: degenerated forward primer (DEN FP), reverse primer (DEN RP); and probe (DEN P): DEN FP 5 AAggACTAgAggTTAKAggAgACCC3 , DEN RP 5 ggCCYTCTgTgCCTggAWTgATg3 and the probe DEN P 5 FAM-AACAgCATATTgACgCTgggARAgACC-TAMRA-3 . RT-PCR conditions for the Light Cycler (Roche Diagnostics) were: RT at 61 C for 20 min, activation at 95 C for 5 min, and 40 cycles of PCR at 95 C for 15 s, 60 C for 60 s. We used the RNA Master Hybridization Probes Kit (Roche Diagnostics) with 500-nM primers and 200-nM probes. The kit includes an aptamer-blocked Thermus thermophilus DNA polymerase, which performs RT and, once the aptamer drops out at activation, hotstarts PCR amplification.",
"gender": "Female"
}
] |
PMC3323263
|
[
{
"age": 85,
"case_id": "PMC3726520_01",
"case_text": "An 85-year-old man was referred to the Aberdeen Royal Infirmary in September 2011 for consideration of corneal grafting due to his poor visual acuity and increasing difficulty with his activities of daily living. He had a history of dry age-related macular degeneration, and FECD. He underwent bilateral phacoemulsification with intraocular lens implants in 1996, and 4 years later was diagnosed with bullous keratopathy. On clinical examination, his best-corrected visual acuities (BCVAs) were OD hand movement and OS 20/200. He had bilateral bullous keratopathy, which was more marked in the right eye. The cornea was edematous with pannus and multiple scars. There was no fundal view but B-scan ultrasonography excluded gross vitreoretinal pathology. The patient was given a guarded prognosis as to the outcome as pre-operative retinal examination was not possible.\nIn November 2011, he underwent an uncomplicated right PK under general anesthetic using a 7.5 mm donor and recipient punch. A vacuum trephine was used to cut through the cornea in a controlled rotatory manner until the anterior chamber was penetrated, confirmed by evidence of aqueous eruption at the wound site. Scissors were used to separate and remove the button and 10.0 nylon interrupted and continuous sutures were placed. Sub-conjunctival dexamethasone and cefuroxime were administered intra-operatively, along with chirocaine in the sub-Tenon's space. Dexamethasone Minims 0.1% and chloramphenicol Minims 0.5% (Bausch + Lomb, Rochester, NY, USA) were prescribed four times daily for the post-operative period. On day 1 and 2 postoperatively, his BCVA OD was hand movement and postoperative anterior chamber inflammation of 3+ cells was found, based on the standard uveitis classification system. At that stage, his steroid treatment was increased to six times a day, along with a Maxitrol ointment (dexamethasone, neomycin sulphate, polymyxin B sulphate; Alcon Eye Care UK Ltd, Surrey, UK) at night. Fundal examination revealed atrophic age-related macular degeneration, which was expected to affect his visual outcome.\nOn the ninth post-operative day, BCVA remained hand movement only in the right eye. A clear gap was apparent between the healthy graft and a thin, transparent sheet of tissue in the anterior chamber. The graft was otherwise clear and this sheet was presumed to be retained DM, as confirmed on histopathology (Figure 1, arrow). Steroid drops were tapered on a monthly basis and his review was arranged for two months with in vivo confocal microscopy testing.\nAt the next clinical review, the graft had remained clear and in vivo confocal microscopy (IVCM) testing, confirmed the presence of DM and healthy endothelial cell count. This was diagnosed as retention of the host's DM rather than a detachment of the donor's DM (Figure 2) as the latter would have been associated with endothelial loss and corneal decompensation. The patient underwent a further uneventful operation for extraction of the retrocorneal membrane under local anesthetic in April 2012.\nPost-operative recovery was uneventful and 2 weeks later, a clear healthy graft with an improved BCVA of OD 20/200 was noted, with the limited acuity more likely related to his atrophic macular degeneration rather than the graft. Further clinical reviews have shown that the graft has remained clear and healthy without any signs of rejection.",
"gender": "Male"
}
] |
PMC3726520
|
[
{
"age": 28,
"case_id": "PMC8526214_01",
"case_text": "Case 1. A 28-year-old woman with no subjective symptoms but had undergone an intrauterine fetal death at 14 weeks gestation. Histopathological examination of the autopsy specimen revealed the presence of Toxoplasma cysts in the placenta, heart, adrenal gland, and brain, so this case was diagnosed as congenital toxoplasmosis. Analysis of antibody levels revealed the following: phyto-hemagglutinin (PHA) antibody:20480 (<160), IgG:5120 (<20), and IgM:20 (<10). There was a serial measuring of antibodies in case 1. IgG and IgM gradually increased, peaked on the 150th day, and IgM became negative on the 310th day.",
"gender": "Female"
},
{
"age": 32,
"case_id": "PMC8526214_02",
"case_text": "Case 2. A 32-year-old woman had a left cervical tumor in five years. She had developed this tumor gradually increased in size recently. We resected swollen lymph nodes and examined microscopically. The lymph node findings showed reactive follicles, clusters of epithelioid cells, and patches of monocytoid cells, which is the triad of Toxoplasma lymphadenopathy. IgG: 320, and IgM: 40; therefore, Toxoplasma lymphadenitis was presumed (case 2, Figure 1).",
"gender": "Female"
},
{
"age": 20,
"case_id": "PMC8526214_03",
"case_text": "Case 3. A 20-year-old woman had developed bilateral cervical tumors that had gradually increased in size over a six-month period. We resected swollen lymph nodes and examined microscopically. The lymph node findings showed reactive follicles, clusters of epithelioid cells, and patches of monocytoid cells, which is the triad of Toxoplasma lymphadenopathy. IgG: 320 and IgM: 20; therefore, Toxoplasma lymphadenitis was presumed (case 3, Figure 1).",
"gender": "Female"
},
{
"age": 44,
"case_id": "PMC8526214_04",
"case_text": "Case 4. A 44-year-old woman had had right cervical tumors for three days. We resected swollen lymph nodes and examined microscopically. The lymph node findings showed reactive follicles, clusters of epithelioid cells, and patches of monocytoid cells, which is the triad of Toxoplasma lymphadenopathy. IgG: 320 and IgM: 40; therefore, Toxoplasma lymphadenitis was presumed (case 4, Figure 1).",
"gender": "Female"
},
{
"age": 23,
"case_id": "PMC8526214_05",
"case_text": "Case 5. A 23-year-old man had lymphadenopathy in both posterior neck and left axilla starting one month previously. PET-CT (positron emission tomography-computed tomography) showed strong accumulation of 18F-FDG (18F-fluoro-2-deoxy-D-glucose), which was consistent with a diagnosis of malignant lymphoma. A 15 mm-sized lymph node was resected from the left axilla and examined microscopically. The lymph node findings showed reactive follicles, clusters of epithelioid cells, and patches of monocytoid cells, which is the triad of Toxoplasma lymphadenopathy. Toxoplasma lymphadenitis was suspected. IgG (EIA): 45 IU/mL (less than 6), and IgM: 8.99 (cutoff index) (<0.80) (case 5, Figure 1).\nThe details of each clinically diagnosed case are as follows:",
"gender": "Male"
}
] |
PMC8526214
|
[
{
"age": 0,
"case_id": "PMC10076737_01",
"case_text": "An 8-month-old girl was admitted to the pediatric department of our hospital after first presenting at the age of 3 months with abnormal facial features that had been noticed within 4 weeks of birth (Figure 1A). Her parents were healthy first cousins. Her prenatal ultrasound examination showed no obvious abnormalities. Because the age of the mother at the expected delivery date was more than 35 years, chromosome microarray analysis by amniocentesis had been performed. The chromosome microarray analysis showed no chromosome number abnormalities or pathogenic copy number variation, and detected eight loss of heterozygosity regions of unknown significance. The mother refused whole-exome sequencing of amniotic fluid owing to the high cost. The patient was born after a full-term pregnancy with a birth weight of 2860 g and an Apgar score of 9-10-10. She had no significant family history and had a healthy 9-year-old sister.\nAt the age of 3 months, physical examination revealed a progeroid facial appearance of coarse facial features with prominent cheekbones and a triangular chin, a low frontal and posterior hairline, and facial hirsutism. She also had hepatomegaly (7 cm in the midclavicular line) with no subcutaneous fat, marked hypertrophy of muscles in the limbs, and acanthosis nigricans. A 3/6 systolic murmur was heard in the precardiac region. Echocardiography showed normal ventricular wall thicknesses (Figure 2A). (interventricular septum (IVS) measured as 4.5 mm, Z score +1.62; left ventricular posterior wall (LVPW) measured as 4 mm, Z score +0.24) and slightly accelerated blood flow in the right ventricular outflow tract (Figure 2B). The preliminary diagnosis was progeria without further treatment.\nAt the age of 5 months, the physical examination findings were similar to the findings at 3 months (Figure 1B). Standard conventional echocardiography performed at the age of 5 months showed myocardial hypertrophy (Figure 2C). (IVS measured as 13 mm, Z score +23.21; LVPW measured as 8.5 mm, Z score +9.1) and an obstructive pattern in the left ventricular outflow tract (Figure 2D) but a normal ejection fraction of 70%. Because the ventricular wall thickness was significantly thicker at the age of 5 months than it was at the age of 3 months, we ruled out the diagnosis of classic hypertrophic cardiomyopathy and considered that the ventricular wall hypertrophy was caused by metabolic factors. Two-dimensional speckle-tracking (2D-STE) was performed to assess strain parameters in the left ventricle and revealed a global longitudinal strain of -16.79% (Figure 3A), a global radial strain of 65.67%, and a global circumferential strain of -14.04%. Abdominal ultrasound showed hepatic steatosis with hepatomegaly. An electrocardiogram revealed sinus rhythm and a prolonged QTc interval (Figure 4). Her blood pressure was 123/65 mmHg. Additional fasting blood testing showed an increased free fatty acid concentration (1.39 mmol/L), normoglycemic hyperinsulinemia (glycemia concentration, 4.60 mmol/L; insulin concentration, 58.53 microIU/mL), dyslipidemia (increased triglycerides [10.14 mmol/L], total cholesterol [5.33 mmol/L], and low-density lipoprotein cholesterol [3.8 mmol/L]), and decreased high-density lipoprotein cholesterol (0.69 mmol/L) indicating insulin resistance. CGL was considered based on the physical characteristics and investigations.\nAt the age of 8 months, 2D-STE showed a decrease in several left ventricular strain parameters (global longitudinal strain, -13.50% (Figure 3B); global radial strain, 37.63%; and global circumferential strain, -14.76%) compared with the values recorded at the age of 5 months despite the findings on conventional echocardiography showing no significant change (IVS measured as 13.5 mm, Z score +23.34; LVPW measured as 8.5 mm, Z score +9.7). Combined with the typical clinical manifestations (severe insulin resistance with lipoatrophy and hypertrophic cardiomyopathy, and hirsutism), exon group of single gene disease-customized capture sequencing test at the age of 9 months identified a homozygous mutation in the BSCL2 gene: c.166_184del (p.Tyr56fs*) (reference sequence NM_032667.6) on 11q12.3, confirming a diagnosis of type 2 CGL (OMIM # 269700).. Both her mother and sister were confirmed to be heterozygous carriers. Dietary modification was introduced to restrict her fat intake to 25% of the total dietary energy. Follow-up biochemistry at the age of 14 months showed progressive improvement in the fasting lipid profile (triglycerides, 4.13 mmol/L; total cholesterol, 5.10 mmol/L; insulin concentration, 29.49 microIU/mL) with normal glycemia concentration [4.5 mmol/L]. Her blood pressure at the age of 14 months was normal. Conventional echocardiography showed no significant changes (IVS measured as 13 mm, Z score +20.55; LVPW measured as 8.5 mm, Z score +7.75) from the findings at the age of 8 months, and the left ventricular strain parameters measured by 2D-STE tended to remain stable (global longitudinal strain, -13.38% (Figure 3C); global radial strain, 34.60%; global circumferential strain, -14.41%).",
"gender": "Female"
}
] |
PMC10076737
|
[
{
"age": null,
"case_id": "PMC10266800_01",
"case_text": "The present study is a clinical case, associated with the research project approved by the Ethics Committee of the Bauru School of Dentistry - University of Sao Paulo, reference number 2235918-CAAE: 71680017.0.0000.5417. The female client was duly informed of the aims and procedures to be adopted in the study and signed the Free and Informed Consent.\nThe client decided to participate in the study due to wanting to undergo a non-invasive treatment to reduce facial wrinkles, having met the following exclusion criteria: realization of invasive facial procedures (plastic surgery, facial filler, botulinum toxin application, laser application) and non-invasive (drainage; massages; medication; new creams, different to those routinely used) in the year prior to the treatments and during participation in the research, a history of skeletal dentofacial deformity, absence of temporomandibular dysfunction, presence of snoring, absence of more than one dental element.\nA speech therapy evaluation was performed before and after the therapeutic intervention. The same physical space, equipment, patient position and room lighting were used to collect the images, as recommended by Frazao and Manzi. The aesthetic and orofacial myofunctional aspects were analyzed using photographic documentation and in video, by two previously trained speech therapists, specialists in orofacial motricity, applying the Orofacial Myofunctional Evaluation Protocol MBGR and the validated scales described in the literature. Following the initial evaluation, we performed nine sessions undertaking electromyographic biofeedback training associated with chewing, swallowing and mild smiling without labial sealing. During this period, isometric and isotonic exercises were also realized in therapy, to condition the cheek, tongue and suprahyoid muscles (3 series of 20 seconds, using the Facial Plus and Lingual-Pro-FonoR exercisers), the palpebral portion of the orbicularis oculi muscle (3 series of 5 seconds, asking the client to open her eyes wide and hold them open, holding the palpebral portion of the orbicularis oculi muscle firmly) and a speaking exercise with a wine cork between the teeth (opening held at the diameter of the cork - requesting the production of three phrases), as a technique for pronunciation (\"speaking with cork\"). The client was asked to carry out these exercises daily at home (eye exercises, twice a day, facial and lingual exercisers and \"speaking with cork\", once a day), as well as using a TransporeTM inelastic bandage once a day while sleeping at night, over the frontal portion of the right and left occipitofrontal muscle, of the right and left eyebrow corrugator muscle and over the inferior orbital portion of the orbicularis oculi muscle (external corner of the eyes - right and left) and during the day, a small strip of latex (2cm long and 5mm in diameter) in the oral vestibule (intersection between the mentalis muscle and the lower lip) except at meals and while sleeping.\nDuring the electromyographic feedback training we used the Biotrainer software on the New Miotec Miotool Face USB NM600FO device. It has eight channels connected to differential active sensors, with 16bit resolution, a 2Khz sampling frequency, 20Hz low pass filter, 500Hz high pass filter, 60Hz notch, a clamp connection, and a reference electrode (ground). To capture the electric signal, we used the same device with Double Trace LH-ED4020 differential passive dual electrodes, with dimensions 44 mm long, 21 mm wide, and 20 mm from center to center, placed over the muscles engaged when chewing, swallowing, and smiling (right and left masseter muscles; major, minor zygomatic region, risorius muscles; orbicularis oris (upper lip); suprahyoids; inferior orbital portion of the orbicularis oculi muscle). The reference electrode (ground) was positioned over the styloid process of the ulna of the right arm. The facial areas and regions where we positioned the electrodes were sterilized with cotton wool soaked in alcohol 77% GL (70% INPM) prior to placing the electrodes for all sessions when electromyographic biofeedback was employed.\nIn the initial evaluation, no alterations to chewing function were observed (a score of zero out of 10, for the MGBR Protocol). For swallowing, a marked contraction of the orbicularis oris and mentalis muscles, during routine swallowing of chewed, solid food and guided swallowing of liquid was observed (score 8 out of 28). The analysis of signs of facial aging showed an absence of static perioral wrinkles (score zero), moderate dynamic perioral wrinkles (score two out of four), moderate nasolabial grooves (score two out of four) and mild labiomentonian grooves (score one out of four). The smile evaluation score obtained using video image capture of the dynamic periorbital wrinkles, in the third execution of the \"open smile\" and of the photographic image of the static periorbital wrinkles in diagonal position (45o), showed accentuated dynamic periorbital wrinkles (score of three out of four) and moderate static periorbital wrinkles (score of two out of four).\nFor training with electromyographic biofeedback, the electrodes were placed in a sequence favoring progressive control by the client of the movements of the different muscle groups when executing trained orofacial functions. As such, to train alternating unilateral chewing in the second session, the electrodes were positioned parallel to the direction of the muscle fiber, over the right and left masseter muscles. For the third and fourth sessions, the electrodes were placed over these muscles as well as over the orbicularis oris muscle (upper lip). This position was maintained for the fifth to the ninth sessions, to train alternating bilateral chewing. To train the swallowing function, initiated in the third session with swallowing pasty food (Greek yogurt), the electrodes were initially placed over the suprahyoid muscle region; in the fourth and fifth sessions electrodes were placed over the orbicularis oris muscle (upper lip); these electrodes were maintained to train liquid swallowing in the fifth session, and chewed solid food in the sixth session, when an electrode over the right and left masseter muscles was added and kept until the ninth session. Figure 1B shows the position of the electrodes for training of chewing and swallowing functions. For smile training initiated in the fifth session, an electrode was placed over the region of the risorius muscle and, for the sixth to the ninth sessions, an electrode on the lower orbital portion of the orbicularis oculi muscle was added. Despite placing the electrodes in the risorius region, the possibility of capturing an electric signal from the adjacent muscles cannot be overlooked (cross talk). Even so, during training it was possible to compare the contraction of the risorius region muscles and the inferior orbital portion of the orbicularis oculi muscle. As such, the client managed to reduce the muscle contractions in the eye region while smiling, with consequent reduction of static and dynamic periorbital wrinkles.",
"gender": "Female"
}
] |
PMC10266800
|
[
{
"age": 0,
"case_id": "PMC8605226_01",
"case_text": "A-3 months-old-boy presented with severe malnutrition, known cholestatic jaundice diagnosed as congenital cytomegalovirus infection and contact of his father who was diagnosed with MDR-TB but was not compliant with his treatment. His tuberculin skin test was positive, chest radiograph revealed right perihilar infiltrate and X-pert MTB/RIF on gastric aspirate was positive for M. tuberculosis complex with resistance to rifampicin. Other baseline investigations revealed a small atrial septal defect on echocardiography, mild to moderate hearing loss on audiology, normal vision and retinas on ophthalmological evaluation, raised bilirubin and liver enzymes (alanine and aspartate transaminases) and positive cytomegalovirus (CMV) IgM with a negative CMV PCR. He was HIV-unexposed and his HIV ELISA was negative, but CD4% was low (19%). Culture of the gastric aspirate eventually was positive, confirming M. tuberculosis resistant to isoniazid and rifampicin on line-probe assay as well as resistant to second-line injectable agents with second-line LPA, but susceptible to the fluoroquinolones. He was therefore confirmed as pre-XDR-TB. The mother's sputum was X-pert MTB/RIF negative. The chest x-ray showed active tuberculosis with infiltrates at the right upper-middle lung field with an increased of bronchovascular marking (Fig. 1). We treated him with five kind of less hepatotoxic anti tuberculosis drugs by individualized treatment based on the updated WHO 2018 guidelines. He commenced the treatment with moxifloxacin (10 mg/kg/day divided in tow dose), linezolid (10 mg/kg/day once daily), cycloserin (10 mg/kg/day once daily), ethambutol (20 mg/kg/day once daily) and para-aminosalysilic acid (200 mg/kg/day divided in two dose). After seven days receiving the pre- XDR-TB treatment, the liver enzymes improved, no adverse reaction such as vomiting, dhiarrea was reported. He also recieved gancyclovir for the CMV infection. He was followed every one month, he shows weight increment to 5.8 kg from 3.6 kg in 3 months and increased gradually every month. His nutritional status improved to normal from severe malnutrition after 20 months of treatment. No adverse reaction such as vomiting nor dhiarrea was reported. The growth and milestones development were appropriate. Laboratory evaluation showed improvement of liver function. Hematologic and neurologic (peripheral and toxic optic neuropathy) adverse effects were monitored during linezolid treatment. No anemia nor thrombocytopenia was found. For the optic toxic neuropathy evaluation, normal vision was concluded through examination of response to light, pupil response, ability to follow a target and ophthalmoscopy examination of the retina was also done to exclude CMV retinitis symptom and the result was normal. The M.tuberculosis culture evaluation result was negative on the first and third month of treatment.",
"gender": "Male"
},
{
"age": 14,
"case_id": "PMC8605226_02",
"case_text": "A-14 years-old-girl presented with severe weight loss (severe malnutrition), with chief complaint of fever since 1 month and hemoptysis since 2 days prior. Her parents showed negative for TB screening. History of tuberculosis contact is her neighbour identified MDR-TB and received treatment in our hospital. Her X-pert MTB/RIF revealed positive Mycobacterium tuberculosis with Rifampicin resistant. Culture M. tuberculosis was positive, confirming M. tuberculosis resistant to isoniazid and rifampicin on line-probe assay as well as resistant to second-line injectable agents with second-line LPA, but susceptible to the fluoroquinolones. The chest x-ray showed active tuberculosis with opacity at the right hilar, lobulated infiltrate in the left apex, nodular at left hilar, and enlarged bilateral peri-hilar lymph nodes (Fig. 2). Before starting the therapy she was consulted to the Psychiatry, Ophthalmology and Ear, Nose and Throat department. Baseline electrocardiography (ECG) showed normal QT interval. HIV screening was negative. She started on individualized drugs regimen for pre-XDR TB with levofloxacin (10 mg/kg/day once daily), ethionamide (15 mg/kg/day once daily), cycloserine (10 mg/kg/day once daily), pyrazinamide (35 mg/kg/day once daily), para-aminosalicylic acid (PAS 200 mg/kg/day divided in two dose), bedaquiline (200 mg once daily for 2 weeks). On the second day receiving bedaquiline, the ECG showed prolonged QT interval >500 ms without any electrolyte imbalance, so bedaquiline was stopped and ECG was examined every day. She started to receive linezolid 400 mg per day (10 mg/kg/day once daily) replacing bedaquiline. There was no more prolonged QT after given linezolid. Laboratory examination and clinical manifestation was monitored due to the side effects of the therapy. During hospitalization no other adverse reaction occurred. The laboratory examination is within normal limit. After two weeks hospitalized, she was discharged. She was followed every one month, no adverse reaction of nausea, vomit, jaundice was reported. Linezolid toxicity was also observed during treatment, hematologic value was normal, no anemia nor thrombocytopenia was found, there were no vision loss and color vision test result was normal (evaluated through Ishihara test). No peripheral neuropathy signs (paresthesia, numbness in extremities) were reported. Her weight increased 2 kg after 3 months treatment and her nutritional status improved to normal weight from severe malnutrition after 20 months of treatment. The M.tuberculosis culture result was negative on the first and third month of treatment.",
"gender": "Female"
}
] |
PMC8605226
|
[
{
"age": 14,
"case_id": "PMC7474778_01",
"case_text": "A 14-year-old male patient presented to our rheumatology clinic with a 4-month history of left hip pain. The pain was more severe in the morning and sometimes woke him up at night and also increased with practicing sports (hockey and lacrosse). His pain is 1-2 of 10 when he is resting and 7-8 of 10 when he is playing sports. There was no history of trauma. There was no associated swelling or morning stiffness, and no pain in any other joints.\nThe patient was initially evaluated in the orthopedics clinic. Initial blood work revealed normal complete blood picture (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Left hip X-ray was normal. Initial MR arthrogram of the left hip showed marked edema of the medial and posterior walls of the left acetabulum (Figure 1). The patient was started on naproxen 220 mg (3.5 mg/kg) once daily, with limited improvement in terms of less frequent waking up at night from pain, knowing this is not optimal dose.\nWith persistence of pain, CT-guided biopsy of the left acetabulum was performed and revealed unremarkable flow cytometry, and histopathology showed cortical bone with rare foci of marrow elements and a mild chronic inflammatory component and no evidence of malignancy. The patient was referred to the rheumatology clinic for further evaluation. Initial examination showed pain with flexion and external rotation with mild limitation of full external rotation of the left hip. JIA and CRMO could not be ruled out given his clinical examination and the histopathology result. The patient was started on prednisone 50 mg (0.7 mg/kg) once daily (that was gradually tapered), and naproxen dose was increased to 375 mg twice daily. Two months later, left hip pain continued, and he started to experience pain of the right hip, right metacarpophalangeal (MCPs), and left clavicle. He was started on weekly methotrexate in addition for presumed diagnosis of JIA and/or CRMO. Bone scan was unremarkable apart from focal increased uptake in the left acetabulum (Figure 2).\nAfter two months of methotrexate treatment, the patient reported improvement in the intensity and frequency of the left hip pain; however, he was still experiencing pain with certain positions. The pain of the right hip, left clavicle, and right MCPs resolved completely. Due to persistence of the left hip pain, adalimumab 40 mg subcutaneous every 2 weeks was added, with no significant improvement in pain. He reported increased need for NSAIDs (twice daily almost every day). Repeat contrast-enhanced MRI showed left hip effusion that decreased from before, with medial focal synovial enhancement and edema of the acetabulum (Figure 3). These findings are not typical for JIA where more diffuse synovial process would be anticipated. Pain was refractory to treatment for presumed JIA and CRMO with NSAIDs, steroids, methotrexate, and adalimumab. Subsequently, CT scan of the left hip was done for further evaluation. It showed 11 x 6 mm low attenuation focus with subtle internal nidus in the posteromedial aspect of the acetabular rim suggestive of intra-articular OO (Figure 4). Steroids, adalimumab, and methotrexate were discontinued. Uncomplicated radiofrequency ablation of the left acetabular OO was performed with complete resolution of the left hip pain.",
"gender": "Male"
}
] |
PMC7474778
|
[
{
"age": 78,
"case_id": "PMC8077606_01",
"case_text": "A 78-year-old man initially presented to our Oncology Unit with an elevated PSA level of 23.3 ng/mL.\nPatient subsequently underwent a transrectal ultrasound guided prostate biopsy which revealed high-risk adenocarcinoma of the prostate with a Gleason score 5 + 5 = 10 involving 60% of the tested tissue.\nMetastatic workup consisting of bone scan showed abnormal concentrations at the level of sacroiliac bones and some metamerians of possible reference to repetitive osteoblastic lesions.\nTo manage bone metastases, the patient had been treated with zoledronate (4 mg).\nHe was then started on ADT (combined androgen blockade therapy using an anti-androgen drug and LH-RH agonist) with leuprolide, as a monthly dose and bicalutamide (150 mg/day) with disease control for 22 months and progressive decrease in PSA value up to 0.22 ng/mL.\nDue to progressive increase in PSA values up to 62.11 ng/mL, treatment was switched to Abiraterone (1,000 mg/day) combined with LH-RH antagonist and prednisone (10 mg/day).\nAfter 3 months of administration of abiraterone, he showed progressive increase in PSA values up to 444 ng/mL, worsening of clinical conditions as asthenia, anorexia, edema and onset of widespread pain.\nThe patient had performance status (PS) with an Eastern Cooperative Oncology Group Grade (G) 2/3.\nA bone scan was performed showing increased bone lesions (Fig. 1a).\nAs a result of poor control of disease with abiraterone, treatment with enzalutamide (160 mg/day) was started.\nAfter 1 month of the administration of enzalutamide, PSA decreased to 3 ng/mL, with improvement in clinical conditions (PS 0) and near-disappearance of pain (Fig. 2).\nThe patient experienced general fatigue while receiving enzalutamide treatment. We evaluated the patient's general fatigue and clarified the quantitative information about this. The patient continued treatment with reduced dosage because of fatigue (80 mg/day). After the administration of reduced dosage of enzalutamide, PSA decreased to 0.3 ng/mL, and the patient reported noticeable improvement in fatigue. A bone scan was performed and showed a favorable response to treatment with overall reduction of pathological bone uptake (Fig. 1b). Treatment with enzalutamide, first at full dosage and then at a reduced dosage, has shown good disease control and a significant improvement in the patient's clinical condition. At time of writing, patient is continuing treatment with enzalutamide with excellent disease control.",
"gender": "Male"
}
] |
PMC8077606
|
[
{
"age": 5,
"case_id": "PMC6005275_01",
"case_text": "We were contacted by a local farmer who kept a cheetah on his farm, which exhibited a slow growing alopecic dermal mass at the height of the left shoulder blade that began to grow approximately 1.5 years earlier (Figure 1). The animal was a castrated 3.5-year-old wild born male cheetah, living since the age of 3 months in a large fenced area surrounding the farmhouse. He had been vaccinated yearly against rabies (Rabisin ), feline calicivirus, feline panleukemia virus, feline viral rhinotracheitis virus (Feligen CRP , Virbac), and feline leukemia virus (Tricat, Nobivac). The surgical option was made. A fine needle aspirate of the mass was not attempted before surgery, as this would have required an additional anesthesia. During the clinical investigation, the cheetah was found in a good health status with a body weight of 47 kg.\nThe cheetah was immobilized with a mixture of ketamine (3.2 mg/kg, Ketavet , Kyron Laboratories, Benrose, RSA) and medetomidine (0.06 mg/kg, Novartis, Spartan, Republic of South Africa) administered with a dart shot from a dartgun (Telinject, Dudenhofen, Germany). The skin around the mass was shaved and the surgical field was washed and disinfected with 70% ethanol. The mass and covering skin were excised from the adjacent tissue. The neoplasia was well encapsulated and no infiltrative growth into the surrounding tissue was visible, but it had one large supportive blood vessel, which was ligated and cut. The wound was closed with a subcutaneous consecutive suture and several cutaneous suture stiches both with absorbable material. The animal was treated prophylactically with 2 mg/kg ketoprofen (Ketofen , Merial) as anti-inflammatory and pain medication and with a combination of 15.000 IU/kg procaine benzyl penicillin and 15.000 IU/kg benzathine benzyl penicillin (Peni-LA Phenix , Virbac) to prevent a wound infection. To keep the wound clean from dust and dirt, we dressed the animal with children's shirt, which was removed by the farmer seven days after surgery. The immobilization was reversed with Atipamezole (0.11 mg/kg, Antisedan , Pfizer, RSA). The wound remained uninfected and was nearly invisible at the annual medical check-up one year after the surgery and the cheetah was still alive 3.5 years after removal of the tumor without any signs of recurrence.\nThe excised neoplasia was fixed in 10% buffered formalin and shipped to Germany in full compliance with the Convention on International Trade in Endangered Species (CITES) for histological examination at the Leibniz Institute for Zoo and Wildlife Research in Berlin.\nThe tumor presented itself as an exophytic firm encapsulated broad based nodular dermal to subcutaneous mass measuring 5.5 cm x 4.5 cm x 2.5 cm, covered by intact sparsely haired dark pigmented skin. Cut surfaces revealed multiple small lobules separated by fine white strands of connective tissue (Figure 2). Lobules were mottled light to dark grey or whitish with multinodular solid growth pattern and they did not exceed the surgical excision margins. Microscopically, some lobules were populated by high numbers of heavily dark brown, pigmented cells, while others contained lightly pigmented cells, which were mostly distributed in the periphery of each lobule (Figures 3(a) and 3(b)). Within the lobules, cells were oriented in cords and trabeculae or small islands separated by thin collagen, while distinct sheets of collagen-rich connective tissue surrounded the entire lobules (Figure 3(c)). Rarely, small assemblies of dark pigmented cells (melanophages) were found in the separating connective tissue septa. The neoplastic cells were cuboidal to polygonal with uniformly large round to ovoid central nuclei with stippled chromatin and 1-2 nucleoli (Figure 3(d)). Cytoplasm was scant to moderate, pale eosinophilic, sparsely stained and finely granular. The majority of the tumor cells had indistinct cell borders (Figures 3(c) and 3(d)). Occasionally, single mitotic figures were found (one per 10 high power fields). The overlying epidermis was made of five to six even layers of unremarkable keratinocytes containing some melanosomes in the basal cells as well as some cells of the stratum germinativum. There was mild orthokeratosis and a few remaining hair follicles. The superficial dermis contained mild nodular perivascular neutrophilic infiltrates and dermal collagen was markedly thickened as a response to the expanding tumor, but no other pathological changes were apparent.\nA panel of immunohistochemistry stains was applied and revealed tumor cells being positive for pancytokeratin but negative for MelanA, S100, and vimentin. Although the dark pigmentation and nests and islands of polygonal cells prompted the differential diagnosis of a melanocytoma, the immunohistochemistry results lead to the final diagnosis of a moderately pigmented basal cell tumor.",
"gender": "Male"
}
] |
PMC6005275
|
[
{
"age": 5,
"case_id": "PMC6472062_01",
"case_text": "A young first time mother at 36 weeks period of gestation was seen in a health clinic in Kuching, Sarawak with regards to her ability to breastfeed. She was referred from a clinic in a small district located around 31 km from the nearest tertiary hospital. She had history of a flame burn at the age of 5 years old to her chest, abdomen, upper limb and part of her trunk. She was admitted for about 4 months in the Burn Unit in a tertiary hospital where skin grafts were done in 3 stages on her whole chest and abdomen. Despite the injuries, she noticed pubertal breasts development. During this pregnancy, she had further breast development which increased in size and her abdomen was able to stretch to accommodate her pregnancy. Physical examination showed a pregnancy which corresponded to her date. The skin over her chest and abdomen appeared tight with areas of hyperpigmentation and hypopigmentation due to scarring from the skin graft. There were normal breasts swelling and breast tissues palpable over her chest with the absence of areola and nipple. Sensations over the skin grafted area were intact. The breasts and abdomen (antenatally) are shown in Fig. 1 (Antenatal: Right breast), Fig. 2 (Antenatal: Left breast) and Fig. 3 (Antenatal: Breasts and abdomen).\nA counselling session was conducted to explore her expectations and hopes regarding her ability to breastfeed her baby. Further counselling was done to prepare her that she might not be able to breastfeed her child due to her physical condition and may need lactation suppression post-birth. Alternative methods of feeding were discussed.\nShe birthed her infant at 36 weeks and 5 days via spontaneous vaginal delivery without any complications. Oral cabergoline 1 mg was given on the first postpartum day to suppress lactation. The baby was given infant formula via bottle feeding as the feeding method of choice. On subsequent days, she noticed her breasts reduced in size.\nAt day 6 postpartum, her breasts reduced in size almost to the pre-pregnancy stage as shown in Fig. 4 (Postnatal Day 6: Breasts).\nA breast ultrasound was done at day 6 postpartum. It showed dilated lactiferous ducts at retroareolar region bilaterally, consistent with lactating ducts of the breasts. The normally appearing vague shadow of the nipple was not seen. However, the tightly packed ducts seen parallel to the ultrasound beam are suggestive of major ducts to the possible location of the nipple as shown in Fig. 5 (Ultrasound: Right breast) and Fig. 6 (Ultrasound: Left breast).\nA discussion with the plastic surgeon was made regarding the possibility of surgery to enable her to breastfeed in her future pregnancies. However, patient was not keen for any surgeries as she was made aware of the risks and complications. She also felt contented with her decision to bottle feed her child with infant formula.\nScheduled home postnatal visits were done to ensure that mother and baby were coping well. She had fully accepted that she was not able to breastfeed her child due to her physical limitations. Her husband and family were very understanding and supportive towards her. The baby was doing well with infant formula feeding. There were no signs and symptoms of postpartum depression.",
"gender": "Female"
}
] |
PMC6472062
|
[
{
"age": 9,
"case_id": "PMC6390555_01",
"case_text": "A forty-nine-year-old female from a suburban community in Sri Lanka presented with insidious high grade intermittent fever with chills and rigors for 2 months. She experienced one to two febrile episodes daily with complete defervescence in between. She also had anorexia, weight loss, sore-throat and symmetrical large joint arthritis without morning stiffness. Small joints and axial skeleton were spared. She also noticed an itchy desquamating erythematous rash over back of the trunk and proximal limbs. Erythematous patches were transient and recurring but did not temporally correspond to febrile peaks. The patient did not have any symptoms referable to a focus of infection and did not report photosensitivity, Raynaud phenomenon, past history of tuberculosis, or high risk sexual behaviours.\nThe patient was averagely built (BMI: 23.1 kg/m2), febrile (39.9 C), ill and pale. A firm 1.5 cm lymph node in the right posterior cervical group was noted. Throat was non-inflamed. Erythematous macules noted over the trunk and proximal limbs were transient. Symmetric arthritis affected elbow, wrist and knee joints. A smooth non-tender 2 cm hepatomegaly was noted. The rest of the examination was unremarkable.\nInvestigations revealed a normocytic normochromic anaemia, neutrophil leukocytosis with toxic changes, reactive thrombocytosis, elevated ESR (110 mm 1st hour), CRP (165 U/L) and ferritin (3200 U/L). Renal function was normal and liver enzymes were mildly elevated (AST 66 U/L, ALT 57 U/L). Auto antibody panel, including rheumatoid factor, antinuclear antibodies (ANA), dsDNA antibodies, pANCA and cANCA were negative. Contrast enhanced computerized tomography of the neck, chest, abdomen and pelvis demonstrated enlarged cervical lymph nodes and fatty liver. Radiographs of large joints were normal. Biopsy of the lymph node showed reactive lymphoid hyperplasia with no evidence of neoplastic changes, suppuration or granuloma. Bone marrow aspiration and trephine showed no abnormalities. Blood and bone marrow cultures for bacteria, tuberculosis, brucellosis, melioidosis and fungi were negative. Serum protein electrophoresis showed polyclonal gamma-globulinaemia and reduced albumin fraction. As she had been exposed to flood water 2 weeks prior to symptom onset (compatible with incubation period of 1-3 weeks) and several cases of melioidosis had been reported in her residential area, antibodies against Burkholderia pseudomallei were tested. It turned positive (1:640, indirect haemagglutination) and titre continued to rise over time (Fig. 1).\nFebrile illness, possible exposure to infectious agents during floods and elevated inflammatory markers necessitated consideration of empiric antibiotic therapy. The patient was treated with ceftazidime (2 g 6 hourly IV) and imipenem (1 g 8 hourly IV) for 14 days and ceftazidime and cotrimoxazole (1440 mg bid orally) for another 14 days, due to positive serology for melioidosis. However she did not show clinical improvement. Fever persisted and inflammatory markers remained elevated. Serum ferritin and melioidosis antibody titre continued to rise exponentially. However repeated peripheral blood cultures for melioidosis did not isolate any bacteria and repeated imaging did not reveal a focus of infection.\nDespite a month of broad spectrum antibiotics she remained febrile with persistently elevated inflammatory markers. In retrospect, AOSD was considered as a possible diagnosis. She showed partial response to NSAIDs, further favouring this diagnosis. Subsequently, she was commenced on high dose steroids (prednisolone 1 mg/kg/day). Within 2 days she achieved complete defervescence and made a good clinical recovery. Serum ferritin level and melioidosis antibody titre declined over time (Fig. 1). After one month of steroid therapy she remained afebrile, but had mild residual large joint arthritis with minimal functional impairment. Methotrexate was commenced and steroids were tapered over next 2 months and at 6 months she remained asymptomatic on methotrexate with normal inflammatory markers. Long term follow up was arranged.\nThe final diagnosis of AOSD was made based on clinical features and exclusion of other connective tissue disorders, neoplasms and infections. During the course of her illness the patient did not develop Macrophage Activation Syndrome, a serious complication of AOSD.",
"gender": "Female"
}
] |
PMC6390555
|
[
{
"age": 25,
"case_id": "PMC4678526_01",
"case_text": "A 25-year-old female presented with a painless and mobile lump in breast measuring 2.5 cm x 2.5 cm. Aspiration cytology of the lump revealed moderately cellular smears comprising of few branching fragments of benign ductal epithelial cells intimately mixed with spherical acellular homogenous hyaline globules [Figure 1a and b]. A few dispersed bare, bipolar cells were also seen in the background. A cytological diagnosis of CS associated with benign proliferative breast disease was given.",
"gender": "Female"
},
{
"age": 59,
"case_id": "PMC4678526_02",
"case_text": "A 59-year-old female presented with a lump in the upper-outer quadrant of left breast measuring 5 cm x 5 cm. The magnetic resonance imaging revealed a heterogeneous noninfiltrating lesion in the left breast. The axilla was clear. The fine-needle aspiration cytology from the left breast lump revealed cellular smears composed of epithelial cells and acellular basement material. The epithelial cells were small and basaloid forming cohesive, spherical, and tri-dimensional structures with a central core of acellular homogenous basement membrane substance [Figure 1c and d]. A cytological diagnosis of ACCB was given. The patient underwent left mastectomy. Mastectomy specimen revealed a 4.5 cm x 4.5 cm x 3.5 cm lesion in the upper-outer quadrant of the left breast. Microscopic examination revealed tumor cells arranged in solid nests, proliferating glands, and cylideromatous differentiation containing eosinophilic basement membrane-like material and basophilic secretions. The areas of cribriform pattern were also seen in the desmoplastic stroma. All resection margins, nipple, and areola, were free from tumor invasion. The histopathology confirmed the cytological diagnosis of ACCB.",
"gender": "Female"
}
] |
PMC4678526
|
[
{
"age": 56,
"case_id": "PMC8791849_01",
"case_text": "A 56-year-old Chinese woman was admitted to our hospital emergency room in September 2020 with repeat fatigue, abdominal distension, and melena for 1 month. Abdominal computerized tomography (CT) suggested obviously uneven thickening and strengthening of the gastric body and gastric antrum wall, possibly accompanied by ulcers and multiple lymph nodes adjacent to the stomach enlarged. Gastroscopic examination revealed a giant ulcerative lesion located in the posterior wall of the gastric antrum, with the invasion of stomach angle and pylorus. Subsequent pathological examination of the biopsy showed poorly differentiated adenocarcinoma. On September 19, 2020, she underwent radical gastrectomy for distal gastric cancer and D2 lymphadenectomy. Pathohistological results of distal gastric cancer resection showed that the tumor was poorly differentiated adenocarcinoma with lymphoid stroma component ( Figure 1 ), without any cancer in the surgical margin and metastasis to regional lymph nodes. An EBV-encoded RNA (EBER) assay demonstrated strong positive staining parallel to the tumor harboring EBV infection ( Figure 1 ). Meanwhile, the immunohistochemistry indicated that MLH1, MSH2, MSH6, and PMS2 were overexpressed (pMMR) and human epidermal growth factor receptor 2 (HER2) was not amplified. The tumor was confirmed as pT4bN0M0 poorly gastric antrum differentiated adenocarcinoma with lymphoid stroma component (EBER-ISH+ and HER2-). The outcomes of next-generation sequencing (NGS) verified fifteen gene mutations ( Table 1 ), a high tumor mutation burden (TMB) with 10.8 Muts/Mb, and microsatellite stable (MSS) status. Immunohistochemical (IHC) data of the tumor tissue suggested that the positive expression of PD-L1 protein and the tumor proportion score (TPS) was 70% and the combined positive score (CPS) was 75 ( Figure 1 ). The immune microenvironment was examined by multiplex immunohistochemical staining and quantitative analysis ( Figure 1 and Table 2 ). Two months after the operation, abdominal CT showed enlargement of mass located in the gastrocolic ligament ( Figure 2 ), which indicated metastatic lymph node (LN). Oxaliplatin 200 mg on day 1 plus oral S-1 60 mg twice a day, from days 1 to 14, along with camrelizumab 200 mg on day 1, repeated every 3 weeks, was administered as first-line treatment. Then, radiographic evaluation was performed every 8 weeks by enhanced CT. The significant resolution of the lymph node was observed after two cycles' exposure of regimen SOX combined with camrelizumab, and the best efficacy evaluation was PR based on RECIST 1.1. Early tumor shrinkage was observed after 8 weeks, and persistent shrinkage of LN was achieved after 4 cycles ( Figure 2 ). From then on, she had been exposed to SOX combined with camrelizumab up to 8 months and still achieved continuous PR. Moreover, the quality of life of the patient was good. Chemotherapy-associated AEs (grade 1 nausea, vomit and grade 2 anemia, grade 2 decreased neutrophil count, and decreased white blood cell count) were observed, and grade 1 reactive cutaneous capillary endothelial proliferation (RCCEP) was presented without any other immune-related adverse event. After 7 cycles' SOX plus camrelizumab, the lesion was still unresectable due to whole abdominal adhesions. After multidisciplinary team (MDT) consultation, the patient underwent external-beam radiotherapy (EBRT) and received 50 Gy/25 fractions. She received S-1 and camrelizumab as the maintenance therapy up to 10 cycles followed by EBRT. Tumor is gradually and continuously shrinking in the latest visit and in deep response with a >80% decrease in size ( Figure 2 ). Until now, PFS reached at least 12 months and the duration of response was beyond 10 months with manageable toxicity.",
"gender": "Female"
}
] |
PMC8791849
|
[
{
"age": 42,
"case_id": "PMC4663175_01",
"case_text": "A 42 year-old Caucasian female was referred for metamorphopsia in the left eye. She had no previous past medical history, did not take any oral or topical medication, and denied travel abroad. Visual acuity was normal in both eyes and examination of the posterior segment revealed a large tortuous choroidal vessel involving the fovea with mild overlying RPE changes (Figure 1A). The red channel of the color fundus photograph clearly highlighted this structure (Figure 1B). Early phase fundus angiography showed early filling of the vessel, confirming its arterial origin (data not shown). Near infrared reflectance (NIR) showed a subtle hyperreflective serpentine-shaped structure temporal to the fovea (Figure 2, left panels). EDI-OCT revealed a thickened choroid and an enlarged vascular structure that spanned the entire thickness of the choroid, from the choriocapillaris to the choroid-scleral junction (Figure 2). Near the fovea, there was an abnormal ellipsoid zone (EZ), including retinal pigment epithelium (RPE) hyperreflectivity, and focal EZ compression with reduced outer nuclear layer (ONL) thickness, as well as an indented choroidal-scleral junction (CSJ, Figure 2). Transverse EDI-OCT sections of the choroidal macrovessel demonstrated its narrowing as it coursed temporally through the macula (Figure 2). False-color en face SD-OCT imaging at the level of the choroid was overlayed on the NIR image, which revealed the path of the macrovessel through the temporal macula (Figure 3).",
"gender": "Female"
}
] |
PMC4663175
|
[
{
"age": 65,
"case_id": "PMC6701301_01",
"case_text": "The patient is a 65-year-old female who was previously diagnosed with moderately differentiated, invasive adenocarcinoma after a right upper lobectomy in 2013. The tumor was positive for EGFR mutation, KRAS wild type, ALK negative, CK7 positive, CK20 negative, and TTF negative. At that time, no chemotherapy or radiation was required. In 2014, the patient had a recurrence of her disease with a metastasis to mediastinal subcarinal lymph node. Over the next four years due to disease progression or inability to tolerate agents (e.g., development of acute pancreatitis from erlotinib), the patient was treated with multiple antineoplastic agents including bevacizumab, pemetrexed, durvalumab, tremelimumab, erlotinib, and afatinib. These were all discontinued over 6 months prior to this admission to the hospital. She also received palliative radiation to the right mediastinal mass as well as to several metastatic spine lesions in the cervical and thoracic spine during 2017. Follow-up staging imaging did not show any evidence of radiation pneumonitis or fibrosis. In early 2018, she underwent biopsy of metastatic liver lesions, found to be adenocarcinoma of the lung primary with EGFR exon 19 deletion and T790M mutations. In April 2018, she was started on Osimertinib 80 mg daily, which she tolerated well for approximately four months. A staging CT was completed in June of 2018, which showed response to therapy as evidenced by a decrease in size of the right infrahilar mass, adenopathy, pulmonary nodules, and hepatic metastases. In addition, her previously noted brain metastasis was no longer seen on her brain MRI. In August 2018, she required an admission to an outside facility due to symptoms suggestive of congestive heart failure. She was diuresed and diagnosed with nonischemic cardiomyopathy. Her heart failure remained well compensated on goal-directed medical therapy and diuretics. Other past medical history is notable for hypertension, acid reflux, emphysema, and iron deficiency anemia. She is not prescribed any antiplatelet or anticoagulation agents. She has several allergies to antibiotics and was previously intolerant to subcutaneous heparin.\nThe patient was admitted to our facility in September 2018 due to progressive dyspnea, fatigue, and weakness of several weeks of duration. She was initially managed as hospital-acquired pneumonia in an immunocompromised host with broad-spectrum antimicrobials, aggressive bronchodilators, and intravenous corticosteroids. Within 24 hours of admission, transfer to the intensive care unit was facilitated due to worsening respiratory distress requiring noninvasive positive pressure ventilation which eventually progressed to require mechanical ventilation. At this time, her exam was remarkable for predominant left-sided rhonchi and rales. Laboratory analysis was unremarkable except a severe acute respiratory acidosis of pH 7.18 and PCO2 of 54 mmHg. Upon arrival, her WBC count was 7.6 x 103/muL, hemoglobin was 8.5 g/dL, and platelets were 305 x 103/muL, and she had normal coagulation panel and B-type natriuretic peptide (BNP). A CT chest with contrast demonstrated a consolidation in the left lung suspicious for pneumonia and small effusions bilaterally with associated atelectasis (Figure 1). Her antibiotics were continued.\nDue to the progressive respiratory failure, a bronchoscopy was performed. The bronchoscopy revealed inflamed airways (left>right) and increasingly hemorrhagic return on sequential lavages (Figure 2) from the lingular segment of the left upper lobe. Bronchoalveolar lavage (BAL) RBC counts were increasing significantly in sequential samples (42,000/muL, 190,000/muL, and 230,000/muL). She was diagnosed with DAH with predominant left-sided parenchymal involvement. She was initiated with pulse dose methylprednisone 250 mg IV every 6 hours for 3 days. Her ventilator settings improved significantly after the initiation of pulse dose systemic steroids. After three days of IV steroids, we decided to repeat the bronchoscopy due to continued small amount of blood-tinged tracheal aspirates requiring in-line suction. On repeat bronchoscopy, the airway inflammation had diminished considerably. There was no visible bleeding. We elected to repeat a sequential lavage in the lingular segment, which was dramatically less hemorrhagic (Figure 3). The RBC counts from the sequential lavage were 5,250/muL, 6,750/muL, and 11,500/muL. Microbiology from BAL was unremarkable. The patient was transitioned to oral prednisone 1 mg/kg daily. She was successfully weaned from mechanical ventilation and eventually discharged from the hospital without a need of any supplemental oxygen.\nA comprehensive standard etiological assessment for DAH was unremarkable including ANCA vasculitis panel and anti-GBM antibodies. Despite her diagnosis of nonischemic cardiomyopathy, the patient was not clinically in decompensated heart failure at any point in her admission. Upon medication review, Osimertinib 80 mg daily was the only new medication the patient had initiated in the prior four months. Osimertinib was discontinued in consultation with medical oncology and was held at her discharge from the hospital. She was discharged on a prolonged prednisone taper. A follow-up CT of the chest demonstrated resolution of the opacities in the left upper lobe (Figure 4).",
"gender": "Female"
}
] |
PMC6701301
|
[
{
"age": 21,
"case_id": "PMC5015501_01",
"case_text": "A 21-year-old man, working as a priest, presented with a history of generalized raised nodular lesions for 2 years. The patient was apparently asymptomatic 2 years back when he started developing reddish raised small lesions over the right knee. The lesions gradually increased in size and then ruptured with blood-stained purulent discharge. There was no loss of sensation. Lesions were not accompanied by pain, itching, or burning sensation. Similar lesions gradually developed over other sites such as left knee, both elbows, and ears. Other symptoms, such as joint pain, swelling of joints, or fever, were absent. The patient consulted a local doctor who advised a biopsy of the lesions. This biopsy report was suggestive of fungal infection; hence, the patient was treated with itraconazole and amoxicillin-clavulanic acid but without any relief. No acid-fast Bacilli (AFB) staining was done.\nOn clinical examination, multiple erythematous nodules and plaques of varying sizes ranging from 3 mm to 3 cm in diameter were seen on bilateral ear pinna and bony prominences of the extremities, i.e., elbows, knees, malleoli, and dorsal aspect of bilateral feet [Figure 1]. Some lesions were covered with hemorrhagic crusts. The lesions were nontender and firm to hard in consistency. The patient had neither oozing of fluid, discharge, sinus, nor ulcers. No history of contact with leprosy patients could be elicited.\nThe blood parameters were within normal limits. Slit skin smears and biopsy from multiple lesions were collected and processed for bacterial and fungal culture since a provisional diagnosis of subcutaneous mycoses was considered. Microscopy as well as culture for both was negative. Slit skin smear received for detection of Mycobacterium leprae was stained by modified Ziehl-Neelsen (ZN) staining using 5% sulfuric acid. Examination of stained smear revealed characteristic AFB in large numbers [Figure 2]. A bacterial index of 4+ (10 AFB per oil immersion field) was recorded. Histopathological examination of skin biopsy showed an unremarkable epidermis with underlying dermis showing a diffuse polymorphous inflammatory infiltrate coexisting with foamy histiocytes, neutrophils, plasma cells, and lymphocytes, extending from dermis to subcutis [Figure 3]. AFB were highlighted by Fite-Faraco stain [Figure 4]. Standard nerve stimulation test was done which showed evidence of mild axonal sensory mononeuritis multiplex in bilateral upper limbs and axonal sensory polyneuropathy affecting bilateral lower limbs with bilateral greater auricular, ulnar, common peroneal nerves showing thickening. This finding supported the microbiological diagnosis of leprosy.\nBased on ZN stain results and histopathological report, the patient was considered as a case of lepromatous leprosy and started on multidrug therapy (MDT). Two months after commencement of MDT, the patient showed improvement with reduction of the nodular lesions.",
"gender": "Male"
}
] |
PMC5015501
|
[
{
"age": 55,
"case_id": "PMC4444167_01",
"case_text": "A 55-year-old male with liver cirrhosis was admitted due to bleeding from gastric varices. Ascites and chronic occlusion of the portal vein (PV) were diagnosed on CT of the abdomen and the patient was referred for TIPS combined with PV recanalization.\nFollowing informed consent and initiation of general anesthesia, a 4 F Cobra catheter (Cordis, Johnson&Johnson, Miami Lake, FL, USA) was placed through the left transjugular access and wedged with a tip in the branch of the right hepatic vein. CO2 injection showed partly patent but very small intrahepatic PV branches and occlusion of the main PV to the confluence of the superior mesenteric vein and the splenic vein. Following replacement of the catheter with a 10-F introducer sheath, several unsuccessful attempts of transjugular transhepatic puncture of the intrahepatic PV branches were carried out using a Rosch-Uchida transjugular liver access set (Cook Inc., Bloomington, IN, USA).\nIn order to facilitate transjugular, transhepatic access to PV, a trans-splenic puncture of the splenic vein branch was performed using a 22-G needle, and a 5-F introducer sheath was placed. Subsequently, a 4-F Cobra catheter jointly with a 0.035-inch glidewire (Terumo, Tokyo, Japan) was manipulated through the splenic vein and into the occluded part of PV in the liver. That catheter was exchanged over the wire for a 6x20-mm dilation balloon (Powerflex Pro, Cordis), and then via the transjugular access, a transhepatic puncture towards the balloon was performed from the right hepatic vein using the transjugular access set. With the use of that access, the tip of the glidewire was advanced into the balloon, and then by pulling back the balloon, the glidewire was advanced to the splenic vein. Following dilation of the tract with a 4x40-mm balloon (Powerflex Pro), a 10-F transjugular sheath was advanced through the transhepatic tract and the recanalized segment of PV. Two Viatorrs (8x80+20 mm and 8x60+20 mm) were deployed coaxially, connecting the SMV/splenic vein confluence with the right hepatic vein. Contrast-enhanced examination showed a short stenosis at the cranial end of the created shunt and repeated balloon dilation was attempted. The 8 x40-mm balloon (Powerflex Pro) inflated partly into the Viatorr was accidentally moved in the cranial direction, causing dislodgement of the cranial part of the endoprosthesis to the right atrium.\nAfter replacing the previous sheath with an 18-F sheath (Cook Inc.), a GooseNeck Snare (EV3, Plymouth, MN, USA) with a 15-mm loop was introduced over the guide wire. The loop of the snare was placed over the cranial edge of the Viatorr (Figure 1). The Viatorr was squeezed and the sheath was advanced over the endoprosthesis. The Viatorr was withdrawn into the sheath and was removed together with the sheath. However, during that withdrawal, the second (coaxially placed in the first one) Viatorr followed into IVC and the removal procedure was repeated as described above (Figure 2). Thereafter, two new Viatorr endoprostheses (8x80+20 mm) were placed in an adequate position, with subsequent good function of the TIPS. The trans-splenic tract was embolized with tva 3x10-mm coils (Cook Inc) and gelfoam pledgets.",
"gender": "Male"
},
{
"age": 43,
"case_id": "PMC4444167_02",
"case_text": "A 43-year-old male with alcohol-related cirrhosis, ascites and bleeding from the varices was referred for TIPS to the Department of Endovascular Surgery of a nearby hospital. CO2 portography was performed in there through a balloon catheter placed in the branch of the middle hepatic vein, showing patent PV.\nDuring transjugular, transhepatic attempt to puncture PV, a bile duct was accidentally entered (Figure 3). That was misinterpreted by the physician performing the procedure, who placed a Viatorr connecting the bile duct to the right hepatic vein. The physician reported later that \"the flow from the SMV was good, the gradient was=0 mmHg, and the TIPS was created successfully\".\nOn the following three days the patient's condition deteriorated and on the fourth day he showed signs of general sepsis and abdominal distension requiring urgent ICU care. The inflammatory parameters were high and the laboratory tests were critically elevated (P-bilirubin=466 mumol/L; CRP=43mg/L; P-creatinine=435 mumol/L). At that time the error was identified and a percutaneous biliary drainage catheter was placed percutaneously through the right liver lobe bile ducts to the duodenum.\nAfterwards, the patient was transferred to the Department of Hepatic Surgery at our hospital, for urgent treatment. Following an interdisciplinary decision and discussion with the patient and his family, it was undertaken to attempt removal of the Viatorr. With the patient under general anesthesia, a paraumbilical vein was punctured using ultrasonographic guidance, and a 4-F Cobra catheter was advanced to the right portal vein branch. CO2 portography through that catheter showed a hepatofugal flow in the portal vein but no connection with the bile duct (Figure 4). The percutaneous biliary drainage catheter was removed over the guidewire and replaced with a 8-F sheath. Through the left jugular vein, a 4-F Cobra catheter was introduced jointly with a 0.035-inch glide-wire through the Viatorr to the common bile duct. After confirmation of their position, the sheath was exchanged over the 0.035-inch Amplatz wire for a 45-cm-long 16-F sheath. The loop of the 15-mm GooseNeck Snare was placed over the wire. Subsequently, a 10x40-mm dilation balloon was advanced into the Viatorr in order to facilitate placement of the snare over the cranial edge of the Viatorr. However, only a part of the cranial portion of the Viatorr could be grasped with the snare.\nThe balloon was deflated and attempt to withdraw the Viatorr into the sheath was performed. About 50% of the Viatorr could be retrieved into the sheath, but then the Viatorr become partly disintegrated and could not be further retracted in the sheath. However, the entire Viatorr could be pulled back from the transhepatic tract to the right atrium (Figure 5).\nThe Amplatz wire tip was withdrawn from the bile duct and advanced to the inferior caval vein (IVC). The right common femoral vein was accessed and another 45-cm-long 16-F sheath was placed with the tip in the IVC. The Amplatz wire was grasped with a 15-mm snare and withdrawn through that sheath. The snare was then advanced over the caudal edge of the Viatorr, which was squeezed and the entire endoprosthesis was pulled back into the sheath in the IVC.\nThe sheath with the endoprosthesis was removed (Figure 6) and hemostasis was obtained with manual compression. A puncture of the portal vein was performed from the transjugular approach towards the tip of the catheter inserted through the paraumbilical vein (PV). The 10x2+8-mm Viatorr was placed in the tract and dilated with a 10x40-mm balloon. CO2 portography confirmed good flow through the TIPS channel and no flow to the bile duct.\nThe sheath in the right lobe bile duct was replaced with an 8-F biliary drainage catheter. Following percutaneous puncture, a left liver lobe internal-external biliary drainage catheter was placed to optimize bile outflow. There were no immediate complications.\nIn the following three weeks, the patient recovered substantially and his laboratory test results normalized. The follow-up evaluation at six weeks showed normal bile ducts and biliary catheters were removed.",
"gender": "Male"
}
] |
PMC4444167
|
[
{
"age": 18,
"case_id": "PMC7537644_01",
"case_text": "An 18-year-old female patient, who was fit and well, presented to the hospital with a three day history of urticarial skin rash that was followed with arthritis and tenosynovitis. Her presentation started with urticaria that failed to improve with antihistamine use. Two days later, she started to have multiple joint pain affecting knees, elbows, shoulders, and ankles in addition to small joints of the right hand. There was no history of preceding insect bite, recent vaccination or medication use. She could not link her symptoms to any particular food. There was no history to suggest any connective tissue disease. The patient had on and off bouts of diarrhea with 5 kg weight loss over five months before her presentation. Two weeks before presenting to the hospital, she had an episode of watery diarrhea with mild abdominal cramps. On examination, there were scattered wheels of urticarial rash. She had tenosynovitis of both the achilles tendons and arthritis with redness, hotness, and detectable effusion mainly in her left wrist and both ankles. In addition to the tenderness of the knees and some of her MCPs.\nHer complete blood count, liver and kidney function tests were normal except for mild microcytic anemia. Her inflammatory markers were high with ESR of 55 mm/1st hour and CRP of 35 mg/L. Autoimmune workup, including rheumatoid factor, antinuclear antibody, and anti-cytoplasmic antibody were negative. Her HLA B27 was negative as well as her serology for brucella, parvovirus, hepatitis B, hepatitis C and HIV. PCR for adenovirus, CMV, EBV was also negative. Urine analysis was normal. Her iron profile showed evidence of iron deficiency anemia with hemoglobin of 9.1 gm/dL. Her stool microscopy showed blastocystis cysts. The patient was started on oral metronidazole 750 mg three times per day for ten days. Her symptoms were controlled by naproxen and prednisolone 30 mg daily, which were tapered off after two weeks with complete resolution of her joint and skin symptoms. Upper and lower endoscopies were done to rule out inflammatory bowel disease (IBD) and were unremarkable except for mild nodular gastritis. Biopsies from the duodenum, ileum and colon showed normal histological appearance. The patient's diarrhea later improved, and she gained 4 kg after five months of follow up with normalization of the inflammatory markers.",
"gender": "Female"
}
] |
PMC7537644
|
[
{
"age": 35,
"case_id": "PMC5380828_01",
"case_text": "A 35-year-old nulliparous patient at 36 weeks of gestation presented to labor and delivery complaining of sudden onset, left sided back pain which radiated anteriorly. She denied any other gastrointestinal or urinary symptoms. The patient had a past medical history significant only for chronic hypertension and a past surgical history of laparoscopic Roux en Y gastric bypass two years priorly. She denied any prior complications related to this surgical history. The pregnancy was further complicated by gestational diabetes class A1. On presentation the patient had a blood pressure of 162/80 and heart rate of 70 beats per minute and was saturating 99% on room air. Initial exam revealed the abdomen to be tender to palpation in left upper quadrant with no guarding and no peritoneal signs. There were no symptoms of labor and fetal status was reassuring.\nComplete blood count, coagulation studies, liver function tests, amylase, and lipase were all within normal limits with a hemoglobin of 12.4 g/dL. A urinalysis demonstrated rare bacteria and calcium oxalate crystals, but no blood. A renal ultrasound showed no evidence of hydronephrosis, mass, or stone. An obstetrical ultrasound revealed a live singleton fetus with a normal appearing anterior placenta and appropriate fetal growth. Intravenous narcotics were required for adequate pain control. General surgery was consulted given her history of gastric bypass and concern for a possible related complication. A CT scan of the abdomen demonstrated a mildly enlarged left adrenal gland with areas of hyperdensity consistent with acute left adrenal hemorrhage (Figure 1). This was a new finding compared with a CT scan performed one year priorly. The patient denied any history of abdominal trauma or anticoagulation. She was admitted to the Surgical Intensive Care Unit where she was comanaged by Maternal Fetal Medicine and General Surgery. She was monitored with serial hemoglobin assessments and abdominal examinations and remained clinically and hemodynamically stable. She was discharged home at 37 weeks of gestation after a 4-day hospitalization and returned for induction of labor at 39 weeks of gestation due to chronic hypertension and gestational diabetes. The patient had an uncomplicated, spontaneous vaginal delivery of a female neonate weighing 7 pounds and 4 ounces with APGARs of 8 at 1 minute and 9 at 5 minutes. Her postpartum course was uncomplicated and interval imaging study to assess resolution of the adrenal hemorrhage was planned.",
"gender": "Female"
},
{
"age": 27,
"case_id": "PMC5380828_02",
"case_text": "A 27-year-old multiparous patient presented to labor and delivery at 38 weeks of gestation for evaluation of sudden onset, left upper quadrant pain that radiated to the midline. The patient also reported regular, painful contractions. She had a past medical history significant for nephrolithiasis during her previous pregnancy, bipolar disease, and migraines. Prior surgeries included a diagnostic laparoscopy for chronic pelvic pain, Loop Electrosurgical Excision Procedure, and 2 elective terminations of pregnancy. The patient was a 5-6-cigarette/day smoker. On admission vital signs were within normal limits. Physical examination revealed her abdomen to be soft and minimally tender to palpation. A complete blood count was within normal limits with a hemoglobin of 12.4 g/dL. A urine drug screen was negative and a urinalysis revealed no blood or evidence of infection. Fetal status was reassuring and an obstetric ultrasound revealed no apparent pathology. The patient's pain improved with intravenous narcotics, antacids, and a muscle relaxer and was attributed to a likely musculoskeletal etiology. However, the patient was found to be in spontaneous labor and progressed to deliver a male infant without complication. Intrapartum pain relief was provided via epidural. On the first postpartum day the patient again complained of left sided flank and upper abdominal pain and was presumptively treated for nephrolithiasis, given the clinical presentation and history, with intravenous narcotics and hydration. Despite treatment, the pain worsened and was associated with nausea and two episodes of emesis. A CT scan of the abdomen revealed enlargement and mild heterogeneity of the left adrenal gland with surrounding fat stranding consistent with acute left adrenal hemorrhage. An MRI performed at the request of the attending physician confirmed these findings as seen in Figure 2. She denied any trauma or use of anticoagulants. Total cortisol level was normal at 14.7 ug/dL with a low ACTH of 5.0 pg/mL. The patient was monitored with serial assessments of hemoglobin and remained clinically and hemodynamically stable. Her pain was controlled with intravenous narcotics. She was discharged on postpartum day 4 with a plan for short interval follow-up. A CT scan performed 8 months later revealed unremarkable adrenal glands with complete resolution of the previously identified hemorrhage.",
"gender": "Male"
}
] |
PMC5380828
|
[
{
"age": 88,
"case_id": "PMC2778822_01",
"case_text": "An 88-year-old female with insidious onset of dyspnea on exertion and occasional nonproductive cough was found to have a 5.7 cm right hilar mass on chest x-ray. A CT-guided biopsy of the soft tissue mass showed a diffuse, monotonous infiltrate of small to medium-sized lymphocytes. Mitotic figures were not significantly increased, with only approximately 5% of the tumor cell nuclei exhibiting Ki-67 reactivity. The predominant lymphocytes were positive for CD20, CD10, and Bcl-6 and negative for CD3 and Cyclin D1 markers. \nBone marrow biopsy was performed to assess systemic involvement. The core biopsy revealed a normocellular marrow for age with a single, paratrabecular lymphoid aggregate (Figure 1), demonstrating similar immunohistochemical staining pattern to that of the right hilar mass. The characteristic features of the malignant cells in the mediastinum and bone marrow were consistent with a stage IV, low-grade, follicular B-cell lymphoma. \nRadiation to the mediastinal mass was initiated with concomitant rituximab treatment (375 mg/m2 for four weeks). No adverse reactions were noted during the first two weeks of rituximab induction. However, the patient developed mild, bilateral ocular pruritis and lacrimation three to four weeks within the induction cycle. Maintenance treatment with rituximab (four weekly doses of 375 mg/m2 every six months) was pursued since the patient tolerated the induction cycle without severe complications. Nevertheless, the bilateral eye inflammation became more pronounced after the second cycle of maintenance therapy. In addition to the pruritis and lacrimation, she also developed intense, bilateral periocular erythema, moderate edema, and pain as well as gradual blurring of vision. These manifestations were more prominent in the left eye. She had neither new lymphadenopathy nor any other systemic symptoms. She was then referred to an ophthalmologist for abatement of symptoms and was given topical steroid drops.\nConcurrent CT of the chest, abdomen, pelvis, and bilateral orbits revealed no evidence of malignancy or disease recurrence. A left eye conjunctival biopsy was performed to further exclude the possibility of an underlying neoplasm. The biopsy showed an intact epithelium, prominent lymphatic channels with increased stromal lymphocytes (Figure 2). The majority of the lymphocytes expressed CD3, a T-cell marker (Figure 3), with only rare cells reactive for CD79a, a B-cell marker (Figure 4). The CD20 stain was negative (Figure 5). \nThe severe ocular symptoms gradually subsided within approximately four to six weeks after the last dose of the second rituximab maintenance cycle. However, mild inflammation of the left eye persisted. Moreover, exacerbation of the left eye conjunctivitis was noted one week after the patient received her initial rituximab dose on the third cycle of maintenance regimen. Rituximab was discontinued, and a followup ophthalmology visit was made. Topical antibiotic and steroid drops were utilized for approximately seven days. Two to three weeks after the termination of rituximab, the patient's conjunctivitis has markedly subsided and has completely resolved in the succeeding eight weeks.",
"gender": "Female"
}
] |
PMC2778822
|
[
{
"age": 18,
"case_id": "PMC7458500_01",
"case_text": "An 18-year-old male was born to consanguineous parents (first-grade cousins) after an uneventful pregnancy by caesarean section (2900 gr birth weight). He had normal early development until 4 years of age. His first symptoms included falls at age 4 years, which became more frequent by 6 years of age and he developed difficulty in climbing stairs. At age 7 years, he progressively lost motor skills. Vision loss and cognitive decline started at around age 8 years.\nNeurological examination showed bilateral optic atrophy, swallowing problems and dysarthria. He had proximal and distal weakness with upper limb amyotrophy, foot deformity and spastic tetraparesis with increased deep tendon reflexes and positive Babinski sign bilaterally. Coordination was impaired, he had limb ataxia and difficulty in walking. He showed urinary and bowel incontinence. He had learning difficulties with dysarthria, delayed speech and language development (Fig. 1).\nElectromyographic findings showed myogenic changes and muscle biopsy revealed cytochrome c oxidase (COX) negative fibers. Laboratory blood results (including CK, ALT, AST, lactic acid) were all normal. Metabolic examinations showed normal organic acids, amino acids and lysosomal enzymes. Cranial MR revealed progressive cerebral atrophy and profound T2 hyperintense periventricular white matter lesions. Additionally, abnormalities of visual and auditory evoked potentials were recorded.",
"gender": "Male"
},
{
"age": 39,
"case_id": "PMC7458500_02",
"case_text": "The patient is a 39-year-old female, born after an uneventful pregnancy without complications to consanguineous parents, both originating from the same small village in Turkey. Her psychomotor development was delayed and she tended to walk on tiptoes. From age 4 years her spastic gait disturbance worsened significantly. At 15 years of age she was still able to walk independently for few meters while requiring a wheelchair to navigate longer distances. At age 27 years her ability to walk was reduced to <10 m with walking aids, around age 30 years she became wheelchair-bound. Her cognitive development was also delayed with delayed speech and language development and a learning disability; after leaving school at 20 years of age she started working at a sheltered workplace.\nNeurological examination at age 39 years showed severely reduced visual acuity, dysarthria, cerebellar ataxia with saccadic pursuits and upper limb ataxia with intention tremor. She had brisk upper limb reflexes, pyramidal signs and reduced fine motor skills of the upper limbs and severe spastic paraplegia of the lower limbs with adductor and knee extensor spasticity ( 3-4 on the Ashworth scale), generalized lower limb weakness (~3/5 on the MRC scale), brisk reflexes and extensor plantar sign. Ophthalmological examination confirmed an optic atrophy, progressive over time; no retinal changes were noted on fundoscopy (Fig. 2). Motor evoked potentials confirmed affection of the corticospinal tracts to upper and lower limbs. Visually evoked potentials demonstrated prolonged P100 latency. Nerve conduction studies were reported normal at age 28 years but indicated a sensorimotor peripheral neuropathy later in the disease course (first noted at age 34, progressive at age 39). Electromyography of the extensor carpi radialis muscle revealed small, short and polyphasic potentials with early recruitment and a full interference pattern, indicating myopathic changes (age 27 years).\nCranial MRI showed slowly progressive confluent T2 hyperintense signal changes of the periventricular and cerebellar white matter and middle cerebellar peduncles with multiple cystic defects, internal cerebral atrophy with dilatation of the lateral ventricles and thin corpus callosum. In the white matter, several areas with disturbed diffusion were noted, only some of which corresponded to areas of ADC reduction. No morphological or signal changes were noted in the area of the basal ganglia (Fig. 2). MRI spectroscopy revealed a strong lactate peak, indicating mitochondrial disease.\nThe probands and unaffected family members were consented for research that was approved by Dokuz Eylul University, School of Medicine Institutional Review Board (family 1) and the University of Tubingen School of Medicine Institutional Review Board (family 2). Informed consent was obtained from all family members that were recruited to the study prior to participation including for whole exome sequencing and the publication of medical information.\nDNA isolation from peripheral blood was done according to a standard protocol. Whole exome sequencing (WES) was performed on DNA obtained from index, unaffected siblings and parentsof family 1 at the Broad Institute of MIT and Harvard, using Illumina Exome Capture Kit (38 Mb target) and in family 2 at the Hussman Institute for Human Genomics (HIHG) at the University of Miami, using Agilent SureSelect Capture (v4, 51 Mb). Sequencing data was processed at the Centro Nacional de Analisis Genomico (CNAG), Barcelona, and data analysis carried out on the RD-Connect Genome-Phenome Analysis Platform (https://platform.rd-connect.eu/genomics) for family 1 and analyzed on the Genesis web-based analysis and collaboration platform (https://www.genesis-app.com) maintained by the Genesis Project Foundation (https://www.tgp-foundation.org) for family 2 using standard filtering criteria for rare diseases, including Minor Allele Frequency (MAF) <0.01, Variant Effect Predictor (VEP) = moderate/high and Combined Annotation Dependent Depletion (CADD) >20.\nWe selected 18 SNPs in TACO1 and in the surrounding genes in the proximity of the c.472insC, p.His158ProfsTer8 mutation. the Sequence information surrounding each of 18 SNPs of interest (and TACO1) was obtained via the USCS genome browser (https://genome-euro.ucsc.edu/index.html) (GRCh37/hg19 assembly) and primers to amplify these regions were designed using the Primer3web application (http://primer3.ut.ee/) (available on request). Purified PCR products were sequenced with an Applied Biosystems 3730xl DNA Analyser. Sequences were analysed using Chromas version 2.6.6.",
"gender": "Female"
}
] |
PMC7458500
|
[
{
"age": 42,
"case_id": "PMC6197703_01",
"case_text": "A 42-year-old woman presented to the clinic with a palpable mass in her left inguinal region which was noticed 1 month prior. The mass had not been present in infancy oradolescence. History of trauma and operations were not found in the patient's history. There was a cyst aspiration story from 2 months ago. On physical examination, a soft-consistency, mobile mass of about 4 cm in size was seen in the left inguinal region. During the Valsalva maneuver, the mass did not change in size and shape. The patient's laboratory findings (complete blood count, urinalysis, blood biochemistry) were within the normal range. Ultrasonography revealed a hypoechoic cystic mass with a size of 40 x 50 mm in the left inguinal area without any vascular flow and no peristalsis (Picture 1).\nAbdominal magnetic resonance imaging (MRI) was performed to examine the communication between the cystic mass and peritoneal cavity, and the precise anatomy around the cystic mass.\nIt was found that the cystic mass in the inguinal canal included thin septa, and hydrocele of the canal of Nuck was suspected because of the low and high signal intensities observed on the T1- and T2-weighted images, respectively. Only the wall and septa were contrast-enhanced. The cystic lesion which was seen to be originated from the inguinal canal was excised in the exploration made by suspending the round ligament by passing through the anatomical folds with the incision made from the left inguinal region (Picture 2, Picture 3).The defect was repaired with prolene mesh after high ligation. Histopathologic examination was evaluated as Simple cystic structure with cubic epithelium (Picture 4). Patient was discharged on the 1 st postoperative day. The patient provided written consent to utilize her medical record with no patient identifiers.",
"gender": "Female"
}
] |
PMC6197703
|
[
{
"age": 58,
"case_id": "PMC4109119_01",
"case_text": "A 58-year-old woman operated with proctocolectomy and an ileal J-pouch 11 years earlier due to ulcerative colitis complicated by colonic cancer presented at a local hospital because of abdominal pain and failure of faecal evacuation. There was a previous history of similar but short and self-resolving episodes of obstruction without clear explanation. A CT-scan aroused suspicion of twisting of the pouch along its longitudinal axis causing an obstruction at the ileoanal anastomosis. An intestinal tube was passed into the pouch for decompression which resulted in relief of symptoms lasting also the day after removal of the tube. She was therefore discharged and referred to our hospital for follow-up with pouchoscopy. However, on the same day as she had been discharged, she presented as an emergency case at our hospital with identical symptoms of obstruction and was admitted to a surgical ward after the application of a tube into the pouch for deflating. Repeated CT-scans at presentation and after application of the tube showed again volvulus of the pouch, which resolved after tube insertion as did the symptoms (Figure 1). Endoscopy of the pouch including 50 cm of the afferent loop was easily done with no signs of ischemia or obvious twisting. The following day a laparotomy was done in order to fixate the pouch to prevent further episodes of twisting. The pouch was found to be enlarged but in its regular position without twisting and not surprisingly there were no adhesions, either in the pelvis or in the abdomen, which made the pouch completely mobile. A loop of the distal ileum was also found to be twisted behind the mesentery of the afferent loop of the pouch as a remaining part of the volvulus (Figure 2). After reduction of the distal ileum a pouchopexy was made with one row of multiple interrupted nonabsorbable monofilament sutures (Prolene) to the presacral fascia as well as closure of the open space behind the mesentery of the afferent loop in the same manner. The postoperative course was uneventful and the patient was discharged.\nTwo months later the patient presented with identical symptoms and a CT-scan showed again volvulus of the pouch. Insertion of a tube on this occasion did not fully relieve symptoms, so this led to a decision to proceed to laparotomy. A volvulus of the pouch along its longitudinal axis was found intraoperatively as well as an accompanying volvulus of the small bowel behind the afferent loop similar to the previous laparotomy (Figure 3). No new adhesions had been formed since that laparotomy and all the sutures to the presacral fascia and retroperitoneum were completely detached except for one. The mildly ischemic pouch and small bowel were derotated and fixated once again to the sacral fascia and retroperitoneum but this time with two rows of continuous multifilament sutures (Ethibond) on either side of the pouch. The sutures were also extended upwards to again close the open space behind the afferent loop mesentery (Figure 4). Furthermore the upper corners of the pouch were sutured to the lateral walls of the pelvis. After an uncomplicated postoperative course, the patient was discharged. At follow-up ten months later she was doing well and was free of symptoms.",
"gender": "Female"
}
] |
PMC4109119
|
[
{
"age": 25,
"case_id": "PMC6744365_01",
"case_text": "A 25-year-old man, previously healthy, was initially admitted due to slowly progressive headache with blurry vision and fever for nine months. The patient recalls ingesting raw camel milk, which is a major risk factor for brucellosis. There was no previous contact with a tuberculosis case. The headache worsened one week before his admission and the patient lost vision in the left eye. His vital signs and cognitive function were normal. Pupils were reactive, but the patient was barely seeing the flash light with his left eye. Ophthalmologic examination revealed an atrophic optic disc mainly with decreased visual acuity bilaterally. Extraocular muscles were intact. The remaining neurological examination was unremarkable.\nHis diagnostic work up showed total white blood cell (WBC) count of 5.61 x 109 cells/mm3 and a C-reactive protein (CRP) level of 3.76 mg/L. His cerebrospinal fluid (CSF) acid fast bacilli (AFB) stain and Mycobacterium tuberculosis polymerase chain reaction (MTB-PCR) were both negative. Blood and CSF cultures were positive for Brucella spp. His serum serological test was positive for B. melitensis and B. abortus. Antibody titers were 1:640 for both strains, just at the cutoff level for the serological diagnosis of the infection. CSF analysis showed elevated WBC count (170 cells/mm3 with 34.9% lymphocytes) and decreased glucose level (34.2 mg/dL). Serum glucose level at that time was 99 mg/dL. CSF protein level was 1.5 g/L while red blood cell (RBC) count was 7 cells/mm3. A magnetic resonance imaging (MRI) of his brain showed multiple, bilateral small dural-based nodular enhancements in both upper frontal lobes (Image 1). The patient was diagnosed with neurobrucellosis. Unfortunately, the patient has completely lost his vision in the left eye with weakened vision in the right eye because of a late presentation and delayed diagnosis. As such, the patient was immediately started on ceftriaxone 2 g intravenously (IV) every 12 h, doxycycline 100 mg orally every 12 h and rifampin 900 mg orally once daily for six weeks along with amikacin 400 mg IV every 12 h for the first three weeks. Three weeks after treatment was initiated, both antibody titers remained at 1:640, which was expected as Brucella antibodies may persist for months after conclusion of therapy. His repeated blood and CSF cultures returned negative a few days after treatment. A repeated MRI of the brain showed interval decrease in the number of the previously reported bilateral frontal leptomeningeal enhancing foci. However, small residual abnormal enhancing foci were still noted. Fortunately, no interval development of new lesions was seen (Image 2).\nUpon completion of the IV regimen (amikacin and ceftriaxone), the patient was discharged on oral doxycycline 100 mg every 12 h and rifampin 300 mg every 8 h to be taken for 6 months. In an outpatient follow up visit three months later, the patient's vision on the right side was slightly improving. While B. melitensis antibody titer slightly decreased to 1:320, B. abortus antibody titer remained at 1:640. Three months later (six months after discharge), a repeated lumbar puncture showed improved CSF analysis with WBC count of 6 cells/mm3, RBC count of 1 cell/mm3, protein level of 0.55 g/L and glucose level of 46.8 mg/dL (serum glucose level was not obtained at the time of this test). Brucella antibody titer in the serum declined from 1:640 to 1:40 for both strains. At this visit, the decision was made to extend the treatment to 3-6 more months to ensure full recovery. Three months later, a repeated brain MRI showed no more meningeal enhancement and CSF analysis was normal; therefore, antibiotic treatment for brucellosis was stopped.",
"gender": "Male"
},
{
"age": 54,
"case_id": "PMC6744365_02",
"case_text": "A 54-year-old woman, known case of type 2 diabetes mellitus and hypertension, was admitted to the hospital due to fever, severe neck and back pain, as well as nausea and vomiting for 2 weeks. She admitted drinking a small amount of raw milk several weeks before her presentation. She had no signs of meningitis and her neurological examination was normal. A lumbar puncture revealed no bacterial growth with CSF protein level of 0.7 g/L and glucose level of 126 mg/dL (serum glucose level was 268.2 mg/dL). CSF WBC count was <1 cell/mm3 and RBC count was 8 cells/mm3. AFB stain showed no Mycobacteria, and CSF MTB-PCR did not detect M. tuberculosis. Urine culture came back negative for any bacterial growth. However, a blood culture was positive for Brucella spp. In addition, both B. melitensis and B. abortus antibody titers in the serum exceeded 1:1280. An abdominal ultrasound was unremarkable. A transthoracic echocardiography followed by a transesophageal echocardiography were both normal. The patient was immediately started on ceftriaxone 2 g IV every 12 h, streptomycin 1 g intramuscularly (IM) once daily, doxycycline 100 mg orally every 12 h and rifampin 300 mg orally every 8 h daily for a total duration of 6 weeks. Her nausea and vomiting were treated with metoclopramide and ondansetron. Her back pain appeared to be due to disc prolapse rather than Brucella spondylodiscitis as was concluded from the MRI of her cervical and lumbosacral areas. After the patient completed 12 days of therapy, she was discharged on doxycycline 100 mg orally every 12 h and rifampin 300 mg orally every 8 h for 30 days and to continue her parenteral antibiotics as an outpatient. Upon follow up one month later, both Brucella antibody titers declined to 1:1280 in the serum. CRP level was 6.93 mg/L (no level was obtained at baseline). The patient was advised to continue the oral antibiotics for 6 more weeks while streptomycin and ceftriaxone were stopped. Two months later (three months post discharge), CRP level increased to 31 mg/L; nonetheless, antibody titers of B. melitensis and B. abortus declined to 1:640 and 1:320, respectively. As the patient appeared asymptomatic and clinically well, her antibiotics were stopped; though, she was advised to remain under supervision and to return for follow up in case of a potential relapse.",
"gender": "Female"
},
{
"age": 31,
"case_id": "PMC6744365_03",
"case_text": "A 31-years-old man who was otherwise healthy presented to the emergency department with high grade fever that persisted for a week but was manageable with acetaminophen (paracetamol). The patient also suffered from headache for three days which he described as being band-like surrounding his head. He reported regular contact with camels and occasional consumption of their raw milk. Three weeks before presentation, he was on vacation in Turkey where he consumed raw dairy products at a rural farm. He was febrile but his physical examination was normal otherwise. Lab investigations revealed a CRP level of 13.5 mg/L and CSF analysis showing a WBC count of 59 cells/mm3 (polymorphonuclear cells of 23% and lymphocytes of 71%), RBC count of 3 cells/mm3, protein level of 0.43 g/L and glucose level of 54 mg/dL (serum glucose was 100 mg/dL). His blood and CSF cultures were negative for Brucella spp. and so were the AFB satin, culture, and MTB-PCR. Nevertheless, his Brucella serum serology revealed an antibody titer of 1:1280 for both, B. melitensis and B. abortus. He was admitted as a case of neurobrucellosis and was started on ceftriaxone 2 g IV every 12 h, amikacin 720 mg (7.5 mg/kg) IV every 12 h, doxycycline 100 mg orally every 12 h and rifampin 900 mg orally once daily. Ten days later, he stared having spikes of fever reaching 40 C, a thorough physical examination and work up were done and they were negative for any potential infection or reason for fever. Thus, antibiotic-induced fever was suspected due to ceftriaxone, thus, it was discontinued despite the overall improvement of the patient's central nervous system symptoms. Ceftriaxone was replaced with ciprofloxacin 400 mg IV every 8 h. As the fever persisted and liver enzymes were noted to increase, rifampin was stopped as well. In less than a week, rifampin was reintroduced. However, 90 min after the dose, the patient experienced shortness of breath, rash, swelling and redness of skin. His reaction was managed immediately with antihistamine and hydrocortisone. This allergic reaction was presumed to be attributed to rifampin; hence, it was stopped and never introduced again. Moreover, the patient also complained of reduced hearing in his right ear which was suspected to be due to an ototoxic effect of amikacin which resulted in its discontinuation. In order to enhance the management of neurobrucellosis, trimethoprim/sulfamethoxazole (TMP/SMX) double strength was started orally; yet, the patient had an episode of vomiting, so it was switched to IV which was well tolerated. Later on, as the patient was being prepared for discharge, IV TMP/SMX was stepped down to the oral formulation again. A lumbar puncture was repeated before discharge and showed an improvement from baseline with WBC count of 4 cells/mm3 (lymphocytes of 86%), RBC count of 9 cells/mm3, 0.33 g/L of protein and 61.2 mg/dL of glucose (serum glucose was not available at this point of time). Repeated antibody titers for B. melitensis and B. abortus were 1:640 and 1:320, respectively. The patient was discharged on doxycycline 100 mg orally every 12 h, ciprofloxacin 750 mg orally every 12 h and TMP/SMX double strength orally every 12 h. In his first outpatient visit one month after discharge, the patient admitted to voluntarily discontinuing TMP/SMX due to severe episodes of vomiting and refused to take it again; however, he continued taking doxycycline and ciprofloxacin which resulted in clinical success (after a total of 18 weeks on doxycycline and 16 weeks on ciprofloxacin).",
"gender": "Male"
},
{
"age": 25,
"case_id": "PMC6744365_04",
"case_text": "A 25-years-old man who was previously healthy came to the hospital complaining of left lower limb pain that progressed to limb weakness with decreased ability to walk. Physical examination revealed moderate lower limb weakness with foot drop. It was worse on the left side with lower motor neuron lesion findings. He had normal sensory exam. He reported drinking raw camel milk three months before the first episode of pain with a family member who was diagnosed with brucellosis recently. There was no tuberculosis contact. Since the patient was suspected to have neurobrucellosis, lumbar puncture was done. CSF analysis showed a WBC count of 420 (polymorphonuclear cells of 4% and lymphocytes of 90%) cells/mm3, RBC count of 18 cells/mm3, elevated protein level at 2.45 g/L and glucose level of 21.6 mg/dL (serum glucose was 81 mg/dL). The CSF culture was positive for Brucella species. The acid fast bacilli stain and culture were negative, as well as the MTB-PCR. Other investigations including tests for hepatitis B and C viruses and human immunodeficiency virus (HIV) 1 and 2 were all negative. Serologically, antibody titers results from the CSF for B. melitensis and B. abortuswere 1:160 and 1:80, respectively. His serum titers were not obtained initially. His CRP level was within normal limits. The patient refused to have a tuberculin skin test. An MRI of lumbosacral spine revealed enhancement of cauda equina nerve roots and surface of thecal sac, as well as L5-S1 degenerative changes with central posterior disc bulge indenting the ventral aspect of the thecal sac with no significant neural compromise associated with intervertebral disc dehydration (Image 3). He was admitted as a case of cauda equina syndrome secondary to neurobrucellosis and was started on ceftriaxone 2 g IV every 12 h, amikacin 500 mg IV every 8 h, doxycycline 100 mg orally every 12 h and rifampin 900 mg orally once daily. The initial plan was to continue the antibiotics with daily physiotherapy then re-evaluate after 6 weeks. However, two weeks into the treatment, the patient's status deteriorated significantly, from difficulty walking to being completely bed bound. Repeated work up showed no other significant findings. Furthermore, after 4 weeks of treatment, the patient started complaining of decreased hearing and pain in both ears resulted in discontinuation of amikacin. Six weeks into therapy, a repeated lumbar puncture did not show a significant improvement with a CSF analysis showing a WBC count of 315 cells/mm3 (polymorphonuclear cells of 41% and lymphocytes of 45%), RBC count of 15 cells/mm3, protein of 3.73 g/L and glucose level of 23.4 mg/dL (serum glucose was 82 mg/dL). Serum antibody titers were 1:320 and 1:80 for B. melitensis and B. abortus, respectively. Since the CSF repeated culture returned negative for Brucella spp., prednisone 1 mg/kg tapering dose was added aiming to reduce further nerve impingement. Luckily, the patient started to show clinical improvement and the IV ceftriaxone was discontinued after completing six weeks of treatment. The patient continued to restore his lower limb power and he was able to transfer to the wheelchair independently. Hence, he was discharged on doxycycline 100 mg orally every 12 h and rifampin 900 mg orally once daily for one year. The patient was scheduled for follow up in both the infectious diseases and neurology clinics. On his outpatient visits, the patient showed remarkable improvement of his lower limb weakness and he restored the ability to walk again using a cane. Serum antibody titers for both Brucella strains were at 1:80 and CRP remained within the normal range.",
"gender": "Male"
},
{
"age": 60,
"case_id": "PMC6744365_05",
"case_text": "A 60-year-old woman with a history of severe osteoporosis and previously treated tuberculous lymphadenitis, presented to the emergency department with fever she was experiencing daily for a month that did not respond to antipyretics. This was associated with frontal headache, night sweats, rigors, chills, generalized body ache, unintentional weight loss of 3-4 kg and pain in the lower back and right leg. She reported regular consumption of raw cheese. Investigational workup was done upon admission where a CSF analysis showed 8 cells/mm3 of WBCs (no differential was done), 12 cells/mm3 of RBCs, 0.36 g/L of protein and 54 mg/dL of glucose (serum glucose was not obtained). Blood CRP level was 36 mg/L. She was admitted as a case of possible bacterial meningitis with suspicion of neurobrucellosis. The patient was started on ceftriaxone 2 g IV daily. Three days later, her blood culture returned positive for Brucella spp., However the CSF culture was negative, as well as the AFB stain. Serological testing for hepatitis B and C viruses and HIV 1 and 2 were all negative. High antibody titers for both B. melitensis and B. abortus of 1:1280 were found in the serum whereas it was negative in the CSF. Ceftriaxone 2 g IV every 12 h was continued and prescribed for 6 weeks along with amikacin 400 mg IV every 12 h for the same duration, as well as doxycycline 100 mg orally every 12 h for 6 months and rifampin 900 mg orally once daily for 6 months. After about two weeks of treatment, lumbar puncture was repeated and the CSF showed no significant changes with WBC count of 7cells/mm3, RBC count of 1 cells/mm3, protein of 0.33 g/L and glucose of 55.8 mg/dL (serum glucose was not available). During hospitalization, the patient felt generally better and became afebrile. After completing the IV antibiotics course (ceftriaxone and amikacin), lumbar puncture was ordered, but the patient refused to undergo the procedure. Consequently, the patient was discharged on doxycycline 100 mg orally every 12 h and rifampin 900 mg orally once daily for 6 months. During her follow up visits, the patient reported feeling well and afebrile with remarkable improvement of the headache. The follow up antibody titer was 1:320 for both Brucella strains, which continued to decrease until it reached 1:160 after completing 6 months of antibiotic therapy. As such, treatment was discontinued.",
"gender": "Female"
},
{
"age": 44,
"case_id": "PMC6744365_06",
"case_text": "A 44-year-old man with a history of recurrent epididymo-orchitis presented to the emergency department complaining of an on-and-off scrotal pain for the last 15 days and low grade fever for which he was given ciprofloxacin for 10 days and acetaminophen (paracetamol) from another hospital. This regimen helped managing his symptoms; however, they were not resolved rendering him seeking medical help at our institution. There were no histories of contact with a tuberculosis patient or raw milk consumption. On physical examination, his scrotum was enlarged, swollen and tender. An ultrasound revealed both testes were of normal size; however, there was bilateral significant increased vascularity in both testicles and both epididymal heads. The scrotal skin was not thickened. There was a slightly increased echogenicity of both testes and a small left hydrocele was identified.\nThere were a few (about four) tiny echogenic foci noted within the left testicle likely representing small calcifications. Physical examination findings of regional lymph nodes and skin were not significant. While awaiting other investigations, the patient was started on ciprofloxacin 400 mg IV every 12 h as an empiric therapy. Blood culture came back negative for Brucella spp.; however, antibody titers were positive for B. melitensis and B. abortus at 1:1280 for both strains. CRP level was 6.8 mg/L. The patient was diagnosed with Brucella epididymo-orchitis, but refused to undergo lumbar puncture for further investigation. Due to lack of clinical improvement, ciprofloxacin was discontinued three days later and was replaced by ceftriaxone 1 g IV every 12 h, doxycycline 100 mg orally every 12 h and rifampin 900 mg orally once daily. After two doses of 900 mg rifampin, the dose was decreased to 600 mg orally once daily though nothing in the patient's notes indicated the reason for the dose change nor the liver enzymes were elevated. After ten days of treatment, ceftriaxone was stopped and the patient was discharged on doxycycline 100 mg orally every 12 h and rifampin 600 mg orally once daily for a minimum period of three months. Before discharge, the patient was clinically improving as demonstrated by the decreased swelling and tenderness of his scrotum. On his first visit as an outpatient 2 weeks after discharge, the patient reported no new complications and appeared clinically well. Tests showed no signs of drug-induced hepatotoxicity, so the rifampin dose was increased to 900 mg orally once daily. On examination, his scrotum appeared to be relieved of the swelling and decreased in size. CRP level decreased slightly to 5.21 mg/L. A week later, the patient came again for follow up. While the patient did not show up for the next visit, his Brucella epididymoorchitis was deemed cured based on the improved clinical findings and decreased CRP. No repeated serology was done.",
"gender": "Male"
}
] |
PMC6744365
|
[
{
"age": 45,
"case_id": "PMC5460377_01",
"case_text": "A 45-year-old female referred to our tertiary care hospital complaining of bilateral knee pain associated with swelling, intermittent generalized body pain that affected her daily activity, progressive painless visual loss in the left eye, and mild headache for one year. She was treated in another hospital symptomatically for bone pain with no improvement. Her past medical history was irrelevant except for vitamin D deficiency.\nOn initial examination, she was afebrile, both knees were tender at joint line, with swelling over the anteromedial aspect of upper part of tibia with erythematous overlying skin. Patellar tap and ballottement tests as well as crepitus test were negative. Visual field testing revealed left homonymous superior quadrantanopia with normal visual acuity. Detailed slit lamp examination was insignificant and showed no involvement of retina. Complete blood count was normal at the time of presentation. Creatinine, urea, and electrolytes were within normal limits. High alkaline phosphatase and normal lactate dehydrogenase were present. Plain X-ray of both knees showed multiple sclerotic patches of the distal femur and upper parts of both tibiae (Figure 1) while bilateral tibia magnetic resonance imaging (MRI) showed bilateral lesions replacing the normal fatty signal intensity in the T1 weighted images (Figure 2). Initial brain MRI showed bilateral well-defined round intensely enhancing lesions located in the temporal poles lateral to the amygdala and anterior to the temporal horns with thickened enhanced pituitary stalk (Figure 3), in conjunction with partially empty sella and absent bright signal of the neurohypophysis (Figure 4). Whole body positron emission tomography (PET) scan showed increased FDG uptake in temporal lobes and facial and long bones (Figures 5(a) and 5(b)). She was further investigated for malignancies, paraneoplastic, autoimmune, neurodegenerative, and toxic causes. All tumor markers were within normal limits.\nLeft tibial biopsy was performed to rule out malignancy and showed marrow infiltration with sheets of foamy histiocytes with the presence of sclerosed trabeculae. The immunohistochemistry showed CD-1a negative histiocytes; however, molecular pathology showed negative BRAF mutation. The clinical, radiological, and immunohistochemical characteristics were consistent with ECD. The patient was started on standard interferon alpha 135 mg per week for a duration of 3 weeks and methylprednisolone with improvement of her symptoms after 1 week.\nOne year later, the patient presented with double vision and left ophthalmoplegia. On examination, she was found to have unequal pupils and papilledema. Brain MRI showed new enhancing lesion in the vicinity of the left cavernous sinus (Figure 6), with pachymeningeal thickening along the tentorial leaflets and interval regression of the mesial temporal lobe lesions.",
"gender": "Female"
}
] |
PMC5460377
|
[
{
"age": 55,
"case_id": "PMC8486010_01",
"case_text": "A 55-year-old-woman with a history of multiple TMJ surgeries presented to our clinic with a chief complaint of limited mouth opening and difficulty bringing her teeth together. Her surgical history was significant for the placement of bilateral PTIPIs in the 1980s, followed by bilateral total joint replacement with Kent-Vitek Inc. (Houston, TX) TMJ prostheses, and most recently removal of the right total joint prosthesis. Her medical history was relevant for fibromyalgia, for which she was on gabapentin 300 mg three times daily, as well as anxiety and depression, which was treated with bupropion 150 mg once daily, duloxetine 60 mg once daily, and alprazolam 2 mg as needed. She also had a history of a large cutaneous ulcer over the right temporal region which was initially thought to have been caused by a foreign body reaction to the implant material, though an incisional biopsy showed findings consistent with trichotillomania.\nExamination revealed right cranial nerve VII deficit, treated with an eyebrow lift, with persistent weakness of the right upper and lower lids of approximately 25-30%. She had bilateral preauricular swelling and well-healed preauricular and submandibular incisions. Her interincisal range of motion was 14 mm, with a gap of 2 mm in her maximally closed position. Her pain score was 7/10 intensity using the Visual Analogue Scale (VAS), with her pain reportedly worst in the right jaw. Radiographic examination with both panoramic radiograph and computed tomography (CT) scan showed partial edentulism of the maxilla and mandible. There was a mass of hypertrophic bone in the right TMJ area. The left mandible showed a total joint prosthesis with the condylar component displaced. Figure 1 shows a panoramic radiograph taken at initial consultation.\nOver the course of a year, she underwent three separate surgeries: (1) prior embolization of the adjacent right maxillary artery, removal of the right heterotopic bone, removal of the left TMJ prosthesis, bilateral TMJ reconstruction with temporary condylar implants (DuPuy-Synthes, Westchester, PA) and abdominal fat grafts to the dead spaces, (2) removal of the temporary implants and placement of custom-made total TMJ implants (TMJ Implants, Ventura, CA) (3) revision of the left TMJ hardware due to instability. The surgical pathology from each of these surgeries showed evidence of foreign material consistent with retained Proplast-Teflon particles with an associated foreign body giant cell reaction. Following the surgeries, the patient showed significantly improved function with an improved range of motion of 34 mm mouth opening as well as the ability to fully occlude her teeth. Figure 2 shows a panoramic radiograph following her series of surgeries. Despite the improved ability to open and close her mouth to speak and eat, she reported persistent pain scored as a 7/10 intensity. She also developed synkinesis of the facial muscles, which responded to treatment with tizanidine 2 mg twice daily.\nThe patient returned three years later with a chief complaint of persistent right-sided pain. Her range of motion was maintained at 35 mm, and her dental occlusion was stable Examination revealed pain on palpation of the right preauricular area and coronoid process. A CT scan revealed no signs of hardware failure. Metal allergy testing for a potential allergy to the prostheses was negative. Serology showed negative rheumatoid factor, antinuclear antibody, and HLA-B27, as well as vitamin D levels within normal limits. Her erythrocyte sedimentation rate and C-reactive protein levels were mildly elevated.\nTo diagnose and treat her pain, collaborative care between her TMJ surgeon, orofacial pain specialist, and neurologist led to various trials of injection therapy (nerve blocks, trigger point injections, and Botox to the right masticatory muscles) and pharmacotherapy (gabapentin, pregabalin, amitriptyline, baclofen, oxcarbazepine, and lamotrigine). The only treatments that brought her relief were right-sided occipital nerve blocks and right inferior alveolar nerve blocks, which reduced her pain from 7-8/10 down to 4-5/10 intensity for several hours. As part of her comprehensive treatment for chronic pain, she was referred to a pain psychologist; however, after undergoing an initial consultation, the patient declined follow-up care.\nOver the course of a year, the patient's pain became more lancinating in nature predominantly in the distribution of the cranial nerve V2 and V3 branches, with pain triggered by touch and cold air, which was concerning for right-sided trigeminal neuralgia. An MRI of her brain revealed no mass lesions or vascular contact leading to compression of the trigeminal nerve. After consultation with a neurosurgeon, she underwent a balloon compression rhizotomy of the right Gasserian ganglion which resolved the lancinating pain.\nFollowing this procedure, she reported a flare of a different type of pain emanating from the right TMJ area. She rated this pain as 8/10 intensity and described it \"like a bad ear infection,\" with pain radiating to \"[her] right cheek, sinus, eye, and forehead.\" She continued on tizanidine 2 mg twice daily, which helped with the muscle pain, as well as baclofen 10 mg three times daily, which reduced pain in the occipital region. She most recently returned to our practice in severe distress with right-sided jaw pain, requesting inpatient admission for pain management and mentioning suicidal thoughts due to her constant pain.\nDiscussion with her primary care physician (PCP) revealed that she had suffered from chronic pain for the 20+ years he had known her, with consequences of social isolation and suicidal ideation having been present throughout this time. Her PCP also stated that trials with different anti-depressants had not been helpful in improving her mood or quality of life. Her orofacial pain team confirmed that suicidal ideation had been a recurring theme and that her long clinical course was in part due to her distrust of medical and surgical providers, the failure of multiple attempts to relieve her pain, and the complications that she suffered from each surgical intervention. Consultation with a psychiatrist specializing in chronic pain led to recommendations of long-term psychological support to help her cope with the pain, with an emphasis on helping her understand the neurobiological connection between depression and chronic pain. Her Prescription Drug Monitoring Program data showed that over the past two years, her opioids and benzodiazepines had been predominantly prescribed by her PCP and she had used one pharmacy. Her mean morphine milligram equivalency (MME) was 62 per day, with occasional spikes to 125 MME, and her mean lorazepam milligram equivalency (LME) was 8.6 per day, with occasional spikes to 17 mg LME.\nUltimately, because she had re-gained a functional range of mandibular motion, no additional surgical intervention was recommended. For pain control, it was recommended that she remain on hydromorphone 2 mg every 4 hours as needed as well as engage in a longitudinal psychiatric program with an emphasis on behavioral health and skills to cope with her pain. The patient agreed that further hospital care would be contingent upon involvement in behavioral health modalities.\nIn 1934, Costen, an otolaryngologist, published an article stating that TMJ symptoms were caused by mandibular displacement as a result of missing posterior teeth. Various iterations of this theory have permeated clinical practice since then and continue to distort our thinking today. Over the following decades, a progressively more scientific approach has been advocated, recognizing the biopsychosocial etiology of these symptoms and the complex nature of these chronic pain conditions, now called temporomandibular disorders.\nOriginally, our understanding of one of these disorders - the painful clicking and locked jaw - was based on our knowledge of anatomy. With the development of imaging techniques, such as arthrography, computed tomography (CT), and magnetic resonance imaging (MRI), surgeons gained the ability to visualize the meniscus of the TMJ at rest and in motion. These imaging modalities supported the notion of internal derangement of the meniscus as pathology and popularized open joint surgery for meniscal repair or repositioning. Thus, presented with a patient in pain with limited range of motion, an image demonstrating derangement and pathology persuaded oral and maxillofacial surgeons (OMFSs) to contemplate surgical repair, although the rationale of these decisions was suspect. Repositioning of the meniscus became a popular intervention but proved to be unreliable in some cases. Accordingly, starting in the mid-1980s, meniscal replacement came into vogue and a variety of materials were used, including ear cartilage, dura, fascia, temporalis myofascial flaps, metal, Silastic, and Proplast-Teflon. It is the PTIPI which is the subject of this review.\nIn 1967, a biochemist named Dr. Charles Homsy was working at DuPont, a chemical and manufacturing company, where he was warned by the company about the dangers of implanted Teflon in the body. In 1968, he developed a material called Proplast, which he would later patent. Dr. Homsy ultimately left DuPont and founded Vitek, Inc. (VI), a small company located in Texas, to develop, manufacture, and market PTIPIs. Proplast was utilized as it is a porous form of polytetrafluoroethylene (PTFE) that allows for infiltration of soft tissue, thereby stabilizing the implant. Teflon, manufactured by DuPont, is a dense form of PTFE and was added to the TMJ interpositional implant to provide a smooth gliding surface across which the mandibular condyle could move. Many years prior, in 1963, a British orthopedic surgeon, Dr. John Charnley, warned against the use of PTFE in joints stating, \"Surgeons, and especially orthopedic surgeons, should be warned that tissue reactions are likely to follow the implantation of polytetrafluorethylene if this material is subjected to abrasion and that these reactions may not be manifest for two years.\" In March 1983, VI notified the United States Food and Drug Administration (FDA), which had authority over the use of implantable medical devices, stating that VI was planning to market the PTIPI for the TMJ, based on the claim that it was substantially equivalent to an existing product (silicone sheeting) that was also being used as a TMJ implant. Its biocompatibility was based on in vitro studies and alveolar ridge augmentation studies. No animal or biomechanical studies were performed until after its introduction into clinical practice, at which time the adverse effects came to light. The FDA agreed, and the PTIPI was allowed to be marketed. \nInitially, there were encouraging reports, with success rates estimated in the 90% range. However, problems were soon reported on the damage that these implants were causing. In 1985, Ryan published a series of 105 joints in 67 patients studied for 25 months, finding that patients who originally had no radiographic or surgical evidence of arthrosis developed varying degrees of arthrosis, and those who had had arthrosis developed progression of their disease subsequent to implantation with PTFE-aluminum oxide implants. In cases of severe arthrosis, MRIs demonstrated loss of signal in the condyle, loss of temporal bone, presence of large soft tissue masses, and fragmentation of the implants. At surgery, all implants were found to be perforated, 50% were folded, and 17% were fragmented or separated into two components. Four cases demonstrated perforation through the temporal bone with exposure of the dura. Histologic studies of the peri-implant tissue yielded exuberant foreign body giant cell reactions with secondary features of chronic inflammation.\nIn 1987, the US Air Force reported problems to VI and the FDA, and in the following year, the FDA conducted its first inspection of VI. Symptoms including pain, radiographic evidence of severe bone loss in the condyle and glenoid fossa, bite changes, limited jaw motion, joint noises, nausea, dizziness, ringing in the ears, fragmentation and/or displacement of the implant, infection, vision and hearing changes, sinus infections and flu-like symptoms were noted. Subsequently, many papers have documented radiographic changes, pathologic reactions, and clinical symptoms.\nAs no complete registry of patients was maintained, the exact number of patients who had PTIPIs implanted is uncertain. Originally VI stated that 12,500 implants were distributed, but an analysis by the District Court of Dallas indicated that the implants were distributed in packs of two, and on that basis, approximately 26,000 units were manufactured and distributed. Data from insurance companies showed a disproportionate number of patients who underwent TMJ surgery were young women between 18-44 years of age. There were also regional differences, with the South being over-represented compared to the Midwest and West/Northeast. Ironically, insurance companies may have contributed to the problem by denying noninvasive treatment modalities for their insureds' TMJ symptoms but covering the surgical procedures.\nThe clinical consequences of the failure of PTIPIs have become quite apparent. Many of these patients now suffer from chronic pain, mandibular hypomobility, and malocclusion because of multiple surgeries. These symptoms affect their activities of daily living, such as talking, eating, toothbrushing, and receiving regular dental care. Severe limitation of mouth opening may also put them at risk of choking if they require emergency intubation. Other studies have documented the subsequent problems that these patients face when they undergo reconstruction of their damaged TMJs. From 1984 through 1998, the FDA received 434 adverse event reports for TMJ implants (all types), 58% of which were associated with patient injuries and 28% of which were device malfunctions. Over 75% of these reports cited two manufacturers, Dow Corning and VI - both of which have ceased production of TMJ implants. The most frequent patient problems reported include surgery to remove the implant, pain, foreign body reactions, and loss of range of motion. A pilot study of surgically retrieved TMJ alloplastic implants similarly demonstrated that pain was a significant symptom associated with perforation of the implants.\nOur own review of 95 patients with end-stage TMJ disease that underwent TMJ replacement with total joint prostheses demonstrates clearly that a subset of patients who had a history of failed PTIPI fared less well than those with other diagnoses (for example, ankylosis, inflammatory disease, and trauma). While on average, the TMJ replacement patients experienced increased range of motion and decreased pain, the subset of 27 patients exposed to PTIPIs was older, had almost twice the number of prior surgeries, had greater limitation of mouth opening prior to surgery, and achieved less range of motion postoperatively, with all of these differences reaching statistical significance.\nThe general health consequences of these failed implants have also been documented. A non-profit patient advocacy organization, the TMJ Association, has documented patient reports of the presence of flu-like symptoms, chronic sinus infections, skin reactions, local and distant lymphadenopathy, as well as immune system problems. In 1999, Baird and Rea reported a small series (n=14) of chronically ill, chemically sensitive patients with multisystem end-order disease and labeled this \"Implant Syndrome Complex.\" Severe pain was the predominant symptom, with all of the 3 patients whose histories were described in detail reporting severe pain.\nFrom the patient's perspective, the aftermath of this event was not properly handled. Many complained that they had not been fully informed of the consequences of the implant surgery or that they were unaware of the recall and need for follow-up. When they were seen by their OMFSs, the evaluation was usually limited to a panoramic radiograph, leading to false reassurances that all was well. When they requested their records, oftentimes they were lost or missing due to office fires or flooding. Patient advocacy groups, newspaper articles, and patient blogs have also told the story of failed implants, multiple surgeries, and continuing symptoms.\nWhile Dupont manufactured and supplied Teflon for the PTIPI, they played no part in the design, specifications, sales, or distribution of the implants. However, they faced 650 lawsuits by 1500 patients in 42 states in the United States and Canada. In almost all of the US cases, they were found not liable for the safety of the VI product and not considered negligent, as \"suppliers of safe multi-purpose raw materials have no duty to warn the ultimate consumer of a finished product about dangers that may exist when the raw materials are integrated into the final product.\"\nVI, on the other hand, which had manufactured and marketed the PTIPI, was the subject of personal injury lawsuits beginning in 1987. They successfully defended the first two suits in jury trials and lost the third in late 1989. The company ultimately declared bankruptcy in 1990. The founder, Dr. Charles Homsy, fled the US and now lives in Switzerland. He blamed the oral and maxillofacial surgery community and patients for the failure of the implants, and the FDA for its restrictive practices. In 1991, the FDA seized the remaining implants and buried them in a landfill in Houston, TX. In 1997, the bankruptcy court settlement with the litigants awarded funds amounting to less than $10,000 per patient. The Judicial Arbitration and Mediation Service/Endispute, Houston reported that 2217 legal claims were made against VI, excluding over 500 who accepted the $1000 settlement as final compensation, with a maximum settlement of approximately $8000. In reviewing the Referee's Report, the example given provided a settlement of approximately $2800 (worth approximately $4769 today).\nOne of the VI OMFS consultants conducted animal experiments after the implant failures were reported. The results were \"essentially catastrophic.\" In a letter to Dr. Homsy, he stated that VI might have a \"calamity of unbelievable proportions on our hands.\" The consultant owned 21,000 VI shares and collected royalties and wrote articles praising VI implants, but eventually conceded that the implants had a predicted in vivo life span of only 3 years.\nThe role of the FDA has been critically evaluated by several authors, and chronologies of these events are available from the FDA among other sources. Figure 3 provides a timeline of the initial manufacturing and clinical application of the VI PTIPI and the role of the FDA in regulating its use, as well as scientific literature published on PTIPIs throughout the years. Since the 1976 Medical Device Amendments were instituted, the FDA has had jurisdiction over medical devices entering the market. Despite PTFE having been condemned by Charnley for joints in 1982, VI filed intent to market PTIPI claiming it to be \"substantially equivalent\" to Silastic, which was already being used in TMJ surgery. Its biocompatibility was based on in vitro studies and alveolar ridge augmentation studies. In 1983, FDA notified VI that the IPI is equivalent to devices marketed prior to the FDA's 1976 Medical Device Amendment and granted 510(k) premarket notification status. Later that year, VI initiated commercial distribution of the implants.\nIn 1987, the US Air Force reported problems to VI and the FDA. In 1988, the FDA became aware of complaints about the PTIPI implants and explants showing bone resorption, implant fragmentation, and delamination, and as a result, conducted its first inspection of VI. In 1989, the FDA issued VI a regulatory letter for medical device reporting and good manufacturing practices violations. In January 1990, the FDA issued a letter to VI advising it to warn all OMFSs against implanting further devices and monitoring their patients until further clinical data were available. Thus, in March 1990, VI issued a \"Dear Doctor\" letter to OMFSs, informing them of the hazards associated with the PTIPI product and advising them to closely monitor all patients through clinical and radiographic examination. The FDA classified this action as a voluntary safety alert. Consequently, VI filed for bankruptcy in June 1990. Shortly thereafter, the FDA issued VI a letter stating that its voluntary safety alert was ineffective, as an audit check had disclosed that some consignees were never notified. In December 1990, FDA reclassified VI's voluntary status alert to a class I recall and issued a safety alert to all OMFSs, urging them to refrain from using the devices and to return all unused devices to the VI bankruptcy trustee. The FDA also rescinded 510(k) status for VI PTIPI, seized the remaining implants and issued a safety alert to all OMFSs. In 1991, the FDA recalled the VI PTIPI - the first recall for this agency - and issued a medical alert to patients. The United States Congress held hearings on TMJ implants in 1992. In 1994, FDA reclassified TMJ Implants as class III devices, subject to premarket approval.\nFDA oversight of the PTIPI has been called into question pertaining to several issues. Because TMJ implants were classified as 510(k) status, they avoided critical review for several years. There was no system to track the devices, as this was not a component of the FDA inspection process. MedWatch was a voluntary reporting system, and in 1986, reports on VI PTIPI were dismissed. The FDA \"seems to have missed several opportunities to intervene and head off the IPI disaster,\" with one oral surgeon reporting, \"The FDA was asleep at the switch.\"\nIn his 1995 Hastings lecture, then FDA Commissioner Dr. David A. Kessler discussed some of the challenges that faced the agency regarding the introduction of medical devices and the role of the FDA \"in piloting their path from the bench to the bedside.\" Citing Shiley heart valves, silicone gel-filled breast implants, and TMJs as examples of problem devices, he explained the several areas for which the FDA was strengthening its activities in product approval, post market surveillance, enforcement, research, and education, noting that \"health care practitioners, too, have a responsibility to let us know when they see problems with a device.\".\nDr. Charles Homsy worked at the Methodist Hospital in Houston, Texas, and developed Proplast in a laboratory there. A lawsuit was filed against the hospital in 1994. The suit was settled in 1996 for $30 million and $975 million in costs. Individual patients were paid between $15,000 and $100,000, in addition to 3% for loss of consortium. The Baylor College of Medicine and the Methodist Hospital were also sued, as tests on components of the PTIPI had been conducted in their facilities and the Methodist Hospital had licensed the manufacture of Proplast to VI. Baylor did not settle and most of the cases were dismissed.\nIn a review of mass tort cases in 1999 based on published sources, TMJ injury claims that PTIPIs led to fragmentation, pain, and bony and soft tissue damage were compared to claims of damage due to breast implants and orthopedic screws. PTIPI claims were far fewer than those against manufacturers of breast implants or orthopedic screws, as the total number of estimated exposures was considerably smaller. However, in the case of PTIPI, the cause of damage was highly identifiable. Notably, PTIPI defendants had a low ability to pay following VI filing for bankruptcy, whereas breast and orthopedic screw implant defendants had a higher ability to pay. By 1999, the PTIPI cases were closed, with the other two categories remaining open. The claims to exposure ratio was similar for the PTIPI and orthopedic screw categories, and much higher for the breast implants.\nThe American Dental Association (ADA) published the FDA safety warning without comment. The American Association of Oral and Maxillofacial Surgeons (AAOMS) sent the FDA safety alert, public health advisory, and TMJ implant advisory to members both in 1992 and 1993. However, the organization took no official advisory position. In 1992, the AAOMS held a workshop on the issue, chronicling the history of AAOMS involvement, reviewing the literature, and offering recommendations for managing patients with alloplastic TMJ implants. The workshop furthermore stated that \"the recommendations presented represent a consensus of the workshop participants and are not an official statement of AAOMS.\" AAOMS later published its first document describing the parameters of care in 1992. Now in its 6th version, the section on TMJ surgery recognizes \"that many patients undergoing TMJ surgeries have unique pain control requirements,\"' and that \"this field has undergone a considerable evolution in the past 15-20 years.\" In regard to alloplastic materials, the document states that \"when alloplastics are used, they should be employed following the manufacturer's instructions and consistent with indications approved by the US Food and Drug Administration.\"\nIn legal disputes, the AAOMS Risk Management group (Oral Surgery National Insurance Company-OMSNIC) defended the profession. At the time, it was headed by an OMFS who had authored an article on 301 patients who had been implanted, and the article blamed the OMFSs and the patients for the implant failures. It was the last article to be published that defended the implant. Many lawsuits were brought against OMFSs who had implanted the device and were vigorously pursued. Figure 4 shows the premise for each side of the debate.\nIn one example of a class action suit brought by 21 plaintiffs and 13 spouses, the plaintiffs filed complaints asserting claims of product liability, breach of warranty, negligence, and loss of consortium. Three of the claims were dismissed; however, negligence both prior and subsequent to the implant surgery was re-evaluated and subsequently hinged on whether the defendants \"failed to include as part of their informed consent process before surgery any mention of all the reports of foreign body tissue reactions, bone resorption, immune reaction, or long-term immunological response.\" After the surgery, the defendants failed \"to provide adequate information from which the claimants could make informed judgments about whether and when to have the Vitek implants removed.\" The case languished in the courts and was ultimately dismissed.\nThe positive and negative results of PTIPI were predominantly published in peer-reviewed OMFS journals. The editor of the Journal of Oral and Maxillofacial Surgery at the time stated that starting in 1986, doctors knew of patients suffering from \"extensive resorption of bone and marked tissue inflammation\" as well as \"intense pain, jaw dysfunction, and occasional changes in the bite.\" He reviewed the FDA's response \"in the instance of the Teflon/Proplast (Vitek Inc., Houston, TX) fiasco\" and concluded \"One can no longer use the issue of FDA approval as an excuse if a device eventually proves to be ineffective.\" In defense of the publication of scientific articles which subsequently turn out to be inaccurate, it can argued that journal editors rely on their reviewers when deciding to publish articles and those views can be biased, ill-informed, or erroneous for a variety of reasons. Furthermore, it is clear that science changes over time and that our view of scientific authenticity can change as a result of new scientific observations as well as other factors.\nAll clinicians are bound by ethical standards that define the framework within which they work. Many articles and guidelines have been published to define these principles, with the four core bioethical principles being respect for patient autonomy, beneficence, non-maleficence, and justice. Embedded within these principles are several items that apply to the PTIPI incident, including: informed consent, truth-telling, good communication skills, ability to exercise sound judgement, research and innovation in surgery, responsible conduct, minimizing harm, recognizing the limitation of one's professional competence, research and auditing, disclosure and discussion of surgical complications including medical errors, and whistle blowing. A full discussion of each of these points is beyond the scope of this article, although in a statement that speaks more directly to this affair, Adedeji and colleagues wrote, \"The surgical profession as a whole has the obligation to improve surgical outcomes and reduce complications by conducting research and participating in systematic programs of quality improvement. This requires keeping detailed and accurate data on the incidence of adverse events.\" Adedeji additionally suggests that the burden of proof for any innovative surgical technique lies with the surgeon, who should be prepared to justify such medical decisions to professional colleagues. Establishing these protocols within an ethical framework is the role of Institutional Review Boards which regulate such activities within medical institutions. Several of the principles were seemingly ignored and ethical issues were insufficiently addressed in the PTIPI affair.\nThe issue of financial reward associated with PTIPIs has attracted very little attention. The companies involved in the manufacture and distribution of these implants as well as their officers, shareholders, and consultants were legitimately in the business for financial gain. Likewise, the OMFSs and the hospitals at which they worked expected to be compensated for their efforts to help patients. For OMFSs, it was \"a bona fide business opportunity.\" It has been suggested that a conflict of interest existed when oral surgeons owned the implants and were subsequently the distributors, as well as the implanting surgeons. The VI recall notice requested that OMFSs \"do not implant any more of these devices if you have any of them in your possession. These implants should be returned for credit. Return these implants to the address below in their original boxes, if available, a copy of the corresponding shipping memorandum.\"\nIt has been reported that the chief VI clinical consultant owned less than 1% of the company's stock and received a royalty payment of 2-4% of the price of certain products sold, amounting to \"about $50,000 a year, he says (although Dr. Homsy pegs it closer to $100,000 some years).\" Hospitals now have conflict of interest policies to which medical staff and surgeons are expected to abide. These typically contain questions regarding financial interests in pharmaceutical and medical equipment companies.\nCurrent thinking about the cause of accidents, adverse events, and near misses in the healthcare field focuses on the several events that need to coincide to create an adverse situation. In any event, hazards exist, and the layers of defense can be breached by latent conditions or active failures, as noted in the \"Swiss Cheese model\" of failure (Figure 5). In the chain of events leading up to the harm that PTIPIs caused, specifically where were the failures?\nSome of the disturbing aspects of the PTIPI incident include the lax regulatory environment at the time, particularly the lack of oversight by manufacturers, such as DuPont, whose products were brought to market by independent companies, such as VI. Importantly, there was a failure of the developers of the PTIPI to recognize or acknowledge the unique features of the TMJ and the empirical literature indicating that this material would fail under loading forces in the joint. In addition, there was a slow and inadequate response of professional organizations, including the AAOMS and ADA, in protecting the public. Furthermore, there was an insistent reliance upon poorly understood technology and an unproven procedure to treat articular disc derangements of the TMJ, which we now know to be a generally self-limiting with a natural history that can resolve over time. The fact that this episode affected a small subspecialty surgical group and a small number of patients, at least in comparison to other implant controversies, in no way mitigates the tragedy of the situation, nor the federal, institutional, and professional responsibilities that were not met.\nThe contrary view supports the decisions made at the time by the OMFSs involved, based on current knowledge and the imperative to treat patients who were in pain, had dysfunction, and were demanding relief. The legal concept of \"standard of care\" evolves over time and is generally considered to be \"what a minimally competent [surgeon] would do in the same situation, with the same resources,\" which turns out to be a fairly low bar in this situation. TMJ surgeries represented relatively simple procedures, with doctors describing the procedure with phrases such as, \"We'll slip this little disc, and you'll be out of the hospital in two to three days.\" The surgeries often presented an alternative to prolonged and ineffective non-surgical treatment modalities that were either failing to alleviate the symptoms or expensive (for example, extensive orthodontic and/or restorative treatment and orthognathic surgery to provide a \"better occlusion\"). In addition, indications for surgery were justified by imaging (CT or MRI) that showed derangement or pathology of the TMJ. Thus, it could be said that the failure of the PTIPI was not so much a problem with the implant material as it was with the OMFSs and patients who did not follow instructions.",
"gender": "Female"
}
] |
PMC8486010
|
[
{
"age": 72,
"case_id": "PMC4488956_01",
"case_text": "A 72-year-old, previously well, woman was found to have left ocular uveal melanoma on ophthalmology review (Fig. 1). She had previously been noted to have 'freckles' on her left retina. At the time of diagnosis the patient was asymptomatic, suffered no visual impairment and declined further investigation, radiotherapy or enucleation. A one-year follow up showed growth of the uveal melanoma with staging undertaken prior to intended radiotherapy. An abdominal CT scan demonstrated a lesion within segments 4 and 7 of her liver (Fig. 1). A Further PET scan showed a focal area of FDG avidity within segment 4 but no increased FDG uptake in liver segment 7,\nA diagnostic laparoscopy was performed for the liver lesions of unknown origin. Intraoperatively, no free intraperitoneal fluid was seen but numerous peritoneal nodules were noted on the diaphragmatic and peritoneal surfaces, particularly in the right upper quadrant. There was no obvious omental disease. These peritoneal nodules along with the liver lesion were biopsied. The liver biopsy showed focally necrotic poorly differentiated adenocarcinoma. Immunohistochemical labeling was in keeping with cholangiocarcinoma and in the absence of a primary site in the extrahepatic biliary system or upper gastrointestinal tract the lesion was considered to likely represent a primary intrahepatic cholangiocarcinoma. The lesion did not label for any immunohistochemical markers for melanoma. The peritoneal biopsy showed nodular proliferations of mesothelial cells with infiltration into the submesothelial adipose tissue indicative of malignant mesothelioma of epithelial type. Immunohistochemistry was positive for mesothelial markers and negative for carcinoma markers.\nThe patient's father and brother had both died of malignant mesothelioma (Fig. 2) having had occupational exposure to asbestos. The patient herself had no occupational exposure to asbestos but may have had ongoing household exposure since the 1970s. Her past medical history was unremarkable besides beta thalassemia minor and a previous hysterectomy for benign disease. The patient was of Greek descent. She was a non-smoker and only occasionally drank alcohol. The patient had four children, and two of these had passed away with renal cell carcinoma and acute lymphocytic leukaemia at ages 41 and 17 respectively (Fig. 2).\nElective surgical resection was deemed appropriate for the patient's primary liver mass. A CT prior to resection demonstrated no change in the liver lesion and no evidence of extrahepatic spread. Intraoperatively, a firm porta hepatic node was identified with frozen sectioning confirming metastatic adenocarcinoma. Fine needle aspiration of the segment 7 also showed adenocarcinoma and in view of positive intra- and extrahepatic disease the liver resection was abandoned. A strip of peritoneum was also removed which again demonstrated malignant mesothelioma.\nIn light of her uveal melanoma and malignant mesothelioma, combined with her family history of mesothelioma it was suspected that the patient might have BAP1 hereditary cancer predisposition syndrome. Testing for BAP1 mutations by immunohistochemistry showed loss of nuclear BAP1 labeling in the primary biliary tract adenocarcinoma, but nuclear labeling for BAP1 was retained in the malignant mesothelioma (Fig. 3). No biopsies were taken from the uveal melanoma. Germline DNA sequencing was performed and revealed the patient to carry a germline missense mutation in the catalytic domain (g.52441252A > G, p.Tyr173Cys) located in exon 7 of the BAP1 gene (Fig. 4). This mutation is predicted to generate a non-functional full-length protein, due to impairment of its ubiquitin hydrolase activity.\nFurther CT surveillance of the patient demonstrated an enlarging liver mass, development of new liver lesions and increasing portacaval lymph nodes. No other distant sites of metastasis where identified on CT. The patient become symptomatic 23 months after the diagnosis of cholangiocarcinoma and mesothelioma and was commenced on palliative chemotherapy. She passed away 31 months after diagnosis of cholangiocarcinoma and mesothelioma due to progression of her intraabdominal malignancies.",
"gender": "Female"
}
] |
PMC4488956
|
[
{
"age": 63,
"case_id": "PMC6402212_01",
"case_text": "A 63-year-old man with chronic kidney disease presented with elevated baseline creatinine. He had no urologic symptoms and no history of flank pain or hematuria. Family history was notable for renal malignancy in the patient's grandmother. The physical examination was unremarkable, with no palpable flank mass or tenderness. Laboratory studies were notable for a creatinine of 2.02 (eGFR = 34 ml/min), up from a baseline of 1.60 (eGFR = 42 ml/min). Renal ultrasound revealed a 12 x 15 cm predominantly solid mass in the right kidney with internal cystic changes and central flow. In the left kidney renal ultrasound revealed a solid-appearing mass in the upper pole measuring 6.5 x 6 x 5.5 cm, a hypoechoic structure measuring 4.8 x 4.1 x 4.6 cm in the lower pole, and an adjacent 6.1 x 5.8 x 6.4 cm solid left lower pole renal mass with a small amount of central flow. Computed Tomography (CT) revealed a 14 x 13 x 16 cm right renal mass almost completely replacing the interpolar region, with significant mass effect on the right kidney (Figures 1 and 2). Adjacent tissue nodularity in the perinephric fat was concerning for satellite nodules or metastatic disease (Figure 1). Right retroperitoneal adenopathy measuring 2.4 x 2.7 cm at the level of the renal hilum was identified. In addition, multiple 2-3 cm hyper- and isodense indeterminate soft tissue lesions were identified in the right kidney. The left kidney was notable for multiple solid renal masses measuring 6.3 cm at the upper pole and 4.6 cm at the interpolar region (Figure 3). A left paraaortic soft tissue mass measuring 4.6 x 4.6 cm with associated calcification was concerning for adenopathy (Figure 3). Whole body positron emission tomography (PET)/CT imaging was obtained to evaluate for metastatic disease. PET/CT revealed bilateral metabolically active solid renal masses concerning for malignancy and metabolic activity in a left paraaortic soft tissue mass concerning for lymphadenopathy. Magnetic resonance imaging (MRI) revealed no evidence of inferior vena cava thrombus.\nThe patient was discussed in a multidisciplinary oncology meeting and the decision was made to proceed with surgical extirpation of the right kidney and the paraaortic mass. We performed an open right radical nephrectomy with right retroperitoneal lymph node dissection and excision of left paraaortic mass.\nGrossly, the right kidney contained a spherical, encapsulated, and homogenous maroon-colored mass with a gray-white lobulated central scar (Figure 4). Two additional smaller masses with similar gross appearance but without central scar were also present. Histologic examination revealed nests of round and polygonal cells with granular, eosinophilic cytoplasm (Figure 5) consistent with oncocytoma. Immunohistochemical staining of the right renal mass with colloidal iron, CD117, CK7, RCC, and CD10 was performed. The tumor cells were positive for CD117, CK7 (Figure 6), and weakly positive for CD10. The tumor cells were negative for Hale colloidal iron and RCC.\nCross sections of the left paraaortic mass revealed a smooth, encapsulated mass with a pearly and glistening tan-white surface (Figure 7). Histologic examination revealed multiple regions of cystic degeneration, positive staining for S100, and Antoni A and Antoni B areas. The final pathologic diagnoses were renal oncocytoma and left paraaortic ancient, benign schwannoma.",
"gender": "Male"
}
] |
PMC6402212
|
[
{
"age": 45,
"case_id": "PMC6497487_01",
"case_text": "A 45-year-old male patient was referred to the prosthodontics clinic to complete the restoration of a dental implant (3.7 mmx11 mm, Zimmer implant, Standard Plus, regular neck, Zimmer Dental, Carlsbad, CA, USA), at the site of tooth #21. The dentist had placed an implant 3 months previously and then started the construction process of a cement-retained crown for restoring implant #21 and fabricated a gold customized implant abutment. Before completion of the implant restoration, the patient was referred to our clinic to continue the treatment.\nDuring the first visit, patient medical and dental history was reviewed. According to the American Society of Anesthesiologists (ASA) physical status classification system, the patient is ASA1. The patient's chief complaint was to continue the treatment of his anterior teeth. Upon smiling, the patient has a low to average smile line. The apparent teeth have a homogenous shade that the patient was satisfied with. Intraoral examination revealed adequate periodontal health, tooth #11 had a provisional crown, and tooth #21 is an implant with a healing abutment. The patient has thin gingival biotype. Radiographic examination displayed the current process of external root resorption for tooth #11. The patient was provided with complete information regarding treatment options to make a decision for tooth extraction and implant placement of #11 (Figure 1). The patient signed an informed consent to proceed with the treatment plan. \nThe cone-beam computed tomography (CBCT) image for the patient displayed sufficient sound buccal, lingual, and apical alveolar bone around tooth #11. A surgical guide was developed as a duplicate for the prior master cast for the prosthodontist with self-cure acrylic resin. The surgeon was guided through predetermined mesiodistal and buccolingual center channel for tooth extraction #11 in the patient's mouth. The implant mount attachment was facilitated with the help of an acrylic transfer jig to assure the cast fabrication for quick succession to fabricate the fixed dental prosthesis after placing an implant. In addition, the vacuum-formed template for provisional restoration fabrication was used for fabricating a 1.5 mm thermoplastic material.\nThe surgical process was performed by the periodontist by giving local anesthesia to the patient. Tooth #11 was removed by performing flapless and atraumatic extraction, followed by normal socket saline rinsing, debridement, and curettage. In addition, during implant drilling, the mouth of the patient was secured through the teeth-supported surgical guide. By using the standard protocols for the Zimmer system, implant placement and bone preparation were performed in the patient's mouth. The placement and torquing of a Zimmer implant were ensured at 40 N cm (Figure 2). In contrast, there was no essential requirement made by the dentist toward soft tissue suturing. \nAfter the implant placement, the transfer jig was secured on the adjacent teeth and the implant mount was carefully connected to the jig by adding autopolymerizing acrylic resin. The implant mount was retrieved from the patient mouth with the attached jig, screwed to an implant lab analog and then transferred to the cast. Two implant temporary abutments from Zimmer (Zimmer Dental, Carlsbad, Calif) were placed on the cast and prepared using the clear vacuum-formed shell template (Figure 3). \nThe implant supported fixed provisional restoration was constructed to develop the preferred emergence profile using acrylic resin. The provisional fixed dental prostheses were appropriately finished and polished.\nThe temporary abutments were screwed to the implants in the patient's mouth, and Teflon tape was used to block both temporary abutments' access holes. Afterward, the minimum amount of non-eugenol temporary cement was used to cement the provisional restoration and excess cement was safely removed. Occlusion was adjusted to ensure minimal contacts during eccentric and centric occlusion (Figure 4). \nPost-operative instruction was given to the patient and recall visits were done after 7 days, 4 weeks, 8 weeks, 12 weeks, and 16 weeks. On each follow-up appointment, the healing was assessed with no signs of inflammation or infection. Also, the development of the soft tissue emergence profile around the implant was monitored and the provisional restoration was adjusted if required. Esthetics and phonetics were evaluated and the patient displayed a complete satisfaction with the outcome (Figure 5). \nA definitive open tray impression was done by using Impergum Penta-Soft after 4 months of healing (Figure 6). The customization of impression copings was based on the transference of the emergency profile of the soft tissue. The soft tissue emergence profile was transferred to the mastercast using light body polyvinyl siloxane material (Figure 7). \nFull contour wax up was made for crowns #11 and 21 on the master cast. The clear vacuum-formed shell template was used to adjust the old gold custom abutment of implant #21. Afterward, mounted master casts, gold abutment #21, and the clear template were sent to Astra Tech (Molndal, Sweden) to design and fabricate a customized milled CAD/CAM Atlantis abutment. Abutment design of implant #11 was requested to match the design of gold abutment #21 except in material. The abutment designed for implant #11 was fabricated from zirconia for comparison purposes. An approval from the prosthodontists was taken via email for the abutment design (Figure 8). A one-piece customized abutment which consisted entirely of zirconia was milled and shipped to the clinic. \nUpon arrival, both abutments were checked on the cast for exact duplication. Full contour acrylic resin crowns were constructed on both abutments to confirm the equal thickness of both crowns on all sections. Thickness evaluation was made using a polygauge and all the readings were equal on both crowns in all sections (Figure 9). \nNext, crowns with porcelain fused to zirconia were constructed for implant abutments #11 and #21. Again, the buccal thicknesses of the final crowns were measured and compared using a polygauge. All readings were comparable for both crowns (Table 1). Afterward, abutments were screwed to both implants and final crowns were checked in the patient's mouth to evaluate esthetics and phonetics. Shade evaluation of both crowns was carried out by the treating prosthodontist on their buccal surfaces (incisor, middle, and cervical thirds) using VITA Easyshade Advance System (VITA Zahnfabrik, H. Rauter GmbH & Co. KG, Bad Sackingen, Germany). All readings were comparable in relation to CIE L*a*b* color space, Classical Vita Shade Guide and 3D Master Shade Guide. The shades of both crowns were comparable and rated clinically satisfactory by the treating prosthodontist and patient. Finally, customized abutments were torqued to 30 N cm, access hale were blocked with Teflon tape, and the final crowns were cemented with non-eugenol temporary cement (Temp Bond NE, Kerr; Orange, CA, USA) (Figure 10). \nTwo experts in fixed prosthodontics who had not taken part in the patients' treatment performed the clinical evaluation. Both observers had good eyesight that will assist in comparing the esthetic appearance of both implants supported all-ceramic crowns with gold and zirconia abutment side by side. Variations were detected using artificial diffuse light and the Vita 3D Master shade guide by standing 50 cm from the mouth of the patient where the head of the patient was positioned upright. There was no difference observed in the color aspect by prosthodontics.\nThe recall visits were done after 2 weeks, 1 month, 3 months, and 1 year from delivery of final restorations. Both implants and their restorations were assessed. The patient was satisfied with the esthetics and functional outcome of the final restorations, as was the prosthodontist (Figure 11). A written informed consent has been provided by the patient to have the case details and accompanying images published. The institution allows publication of the patient's treatment and images for scientific purposes.",
"gender": "Male"
}
] |
PMC6497487
|
[
{
"age": 42,
"case_id": "PMC4257017_01",
"case_text": "A 42-year-old Caucasian woman was referred to our department complaining of sudden vision loss, watery discharge from her right eye (RE), and pain. She had a complex past ocular history that included the implantation of Retisert in her RE to treat persistent uveitis-associated cystoid macular edema on the background of psoriatic arthritis 18 months earlier. In addition, according to her notes, she had undergone combined phacoemulsification and vitrectomy with epiretinal membrane peeling 2 years before the FA implant. One year after the Retisert implantation, she underwent right trabeculectomy to treat persistently high intraocular pressure.\nOn examination, the intraocular pressure (IOP) was 2 mmHg, the anterior chamber was flat, and the visual acuity was counting fingers in the RE. An anterior segment examination revealed scleral melt with active leaking (positive Seidel test) at the site of the FA implant. The patient underwent urgent surgical repair under general anesthesia. Intraoperatively, an anterior chamber maintainer was used and surgical exploration confirmed significant scleral melt at the site of implantation with leaking aqueous humor (Figure 1). A scleral patch graft was sutured over the leaking sclerotomy.\nOn the following day, the IOP was 9 mmHg and the fundus examination revealed that the FA implant had detached from the scleral sutures and was free floating in the vitreous cavity.\nThree weeks later, the IOP was 18 mmHg, the visual acuity recovered to 20/30, and the patch graft was in good position (Figure 2). Benefits and risks of vitrectomy to remove the Retisert implant were discussed with the patient; however, she decided against surgery.\nTwo years later, visual acuity remained 20/30 with no recurrence of the cystoid macular edema, and IOP within normal limits, without additional medication.",
"gender": "Female"
}
] |
PMC4257017
|
[
{
"age": 53,
"case_id": "PMC4996063_01",
"case_text": "A 53-year-old wheelchair-bound man presented with a cT4aN0M0 right lower gingival squamous cell carcinoma (53 x 36 x 40 mm). He had suffered from childhood-onset poliomyelitis that was complicated with atrophy of both the lower extremities. His medical history included pure motor lacunar infarction with left hemiplegia for 5 years, with preoperative, bilateral, Grade 4 lower limb muscle power using the Medical Research Council's grading system. Tumor ablation, segmental mandibulectomy from the symphysis to the right ramus, and a right supraomohyoid neck dissection were performed, resulting in a through-and-through right buccal defect. A reconstruction plate was used to reinforce the strength of the mandible (Figure 1). The right buccal defect was reconstructed using a left ALT-free flap with a portion of the vastus lateralis muscle and six cutaneous perforators. The skin paddle for the mucosa defect measured 8 x 8 cm and for the cheek defect measured 11 x 9 cm in a snowman configuration. The descending branch of the lateral circumflex femoral artery was anastomosed to the right superior thyroid artery, and the two comitant veins of the descending branch of the lateral circumflex femoral artery were anastomosed to the right superior thyroid vein and a branch of right internal jugular vein. A split-thickness skin graft was harvested from the left medial thigh and was used to close the donor site defect. The flap survived, and the patient's post-operative course was uneventful. The total duration of hospitalization was 11 days. After 2 years and 11 months of follow-up, the flap has a bulky appearance but there is no exposure of the reconstruction plate or trismus, and the grafted donor site is unobtrusive (Figure 2). The bilateral lower limb muscle power remained at Grade 4.",
"gender": "Male"
},
{
"age": 51,
"case_id": "PMC4996063_02",
"case_text": "A 51-year-old man with atrophy of the muscles in both the lower extremities (Figure 3) presented with a cT4aN0M0 left buccal squamous cell carcinoma (35 x 23 x 20 mm) with skin invasion. He had suffered from poliomyelitis in his childhood, which was followed by a flexion contracture of both the hips and knees. He underwent operations to release the flexion contracture of his hips and knees approximately 40 years ago and could walk well with calipers and crutches. The preoperative muscle power in his right and left lower limbs was Grade 0 and 1, respectively. Wide tumor excision, marginal mandibulectomy, and left supraomohyoid neck dissection were performed, resulting in a through-and-through left buccal defect. An ALT-free flap that included a portion of the vastus lateralis muscle was harvested from his right lower limb to reconstruct the buccal defect. The skin island measured 20 x 10 cm and included two cutaneous perforators (Figure 4). The descending branches of the lateral circumflex femoral vessels were anastomosed in an end-to-end fashion to the left superior thyroid artery and two comitant veins. The donor site was resurfaced using a split-thickness skin graft that was harvested from the right medial thigh. Arterial vasospasm occurred intraoperatively and was subdued using 2% xylocaine irrigation. The flap became pink in color, and the capillary refill returned to a normal level (Figure 5). Post-operatively, intravenous infusion of prostaglandin E1 was prescribed to promote skin flap blood flow. The flap survived, and the patient's post-operative course after 17 days of hospitalization was uneventful. At the 3-month follow-up, the patient was satisfied with the reconstructed cheek and there were no donor site complications. The muscle power in the right lower limb remained at Grade 0 and he could walk well with calipers and crutches (Figure 6).\nA line was drawn between the anterior superior iliac spine and superolateral corner of the patella, and a longitudinal skin incision of approximately 3-4 cm was medially made using normal procedures. A skin incision down to and through the thigh fascia will expose the rectus femoris in the normal lower limb but may encounter the vastus medialis muscle in a patient with poliomyelitis because of significant muscle atrophy. The quadriceps muscle had a pale, yellowish, fat-like color (Figure 4), and the intermuscular septum was not clear. Inexperienced surgeons may mistake the vastus medialis muscle for the rectus femoris muscle. In a patient who has had poliomyelitis, a lateral 1-2 cm subfascial dissection is required to clearly identify the rectus femoris muscle. Following identification, the dissection proceeded along a subfascial plane laterally toward the intermuscular septum between the rectus femoris and vastus lateralis muscles. Medial retraction of the rectus femoris muscle revealed the vascular pedicle with a descending branch of the lateral circumflex femoral vessels. In our experience, the diameter of the vascular pedicle is less than 1 mm and smaller in patients with a history of poliomyelitis compared with patients without a history of poliomyelitis. The thigh skin was then raised and laterally retracted by a subfascial plane dissection, exposing the septocutaneous and/or musculocutaneous perforators. The number and size of cutaneous perforators were similar to normal ambulating limbs. Distal to proximal intramuscular dissection of the musculocutaneous perforator was then initiated. The intramuscular dissection was easier and more rapid than in a normal limb because there were fewer vastus lateralis muscle branches and less muscle bleeding. The distal end of the descending branch of the lateral circumflex femoral vessels was ligated, and a thigh fasciocutaneous or myocutaneous ALT flap was well prepared for harvesting.\nOn pathological examination of the paralytic limbs in Case 2, the thigh skin tissue revealed chronic inflammatory cell infiltration and fibrosis. As expected, the evaluation of the vastus lateralis muscle revealed degeneration and fibrosis (Figure 7).",
"gender": "Male"
}
] |
PMC4996063
|
[
{
"age": 29,
"case_id": "PMC8795594_01",
"case_text": "A 29-year-old Chinese woman was referred to the ophthalmology clinic, complaining of gradual painless visual loss associated with intermittent episodes of whiteout of vision in both eyes for 1 month. Her visual disturbance was more prominent in the left eye and worsened upon standing. She also experienced headaches, dizziness, weakness in the left extremities, and jaw claudication while chewing. Two years prior to presentation, she had noted diminished left radial pulse. There was no contributory family history. She had been diagnosed with Type 5 TA 1 month prior to our ophthalmology clinic and received two courses of intravenous cyclophosphamide (CTX) with a 4-week interval followed by oral prednisone.\nAt presentation, general physical examination disclosed the absence of left radial arterial pulses, along with feeble arterial pulses on her right side. Carotid and subclavian bruits were heard on both sides. Her blood pressure was 145/71 mmHg in the lower extremities. Ocular examination revealed a decimal best-corrected visual acuity (BCVA) of 0.02 and 0.4 in the right and left eyes. Intraocular pressure (IOP) was 6.3 mmHg in both eyes. Slit-lamp examination showed that anterior segment was unremarkable. Fundus examination revealed mildly distended veins in both eyes ( Figure 1 ).\nFFA of the left eye showed delayed choroidal filling, leading edge of fluorescein dye in the arteries, prolonged arm-to-retina circulation time of 38 s, and arteriovenous transit time of 32 s. Diffuse microaneurysms were noted in the midperipheral area. In the late phase, retinal vessels were markedly stained. Similar changes were detected in the right eye. There was no evidence of capillary non-perfusion, arteriovenous shunts, or retinal neovascularization ( Figure 2 ). Spectral domain OCT (SD-OCT) did not detect any significant macular changes. OCTA showed extreme rarefaction of perifoveal vascular density at the level of superficial capillary plexus (SCP) ( Figures 3A, G ) and deep capillary plexus (DCP) ( Figures 3D, J ) in both eyes. Disruption of the perifoveal vascular arcade was also noted predominately in DCP.\nBlood testing on admission revealed normal erythrocyte sedimentation rate (8.0 mm/h), C-reactive protein (2.40 mg/L), and moderate eosinophilia (7,460 cells/mul). Chemical profile, liver and renal function, antinuclear antibody, antineutrophil cytoplasmic antibodies, and rheumatoid factor were normal. On vascular imaging, a carotid Doppler showed diffuse wall thickening with associated luminal stenosis involving bilateral common carotid arteries and subclavian arteries. High-grade stenosis of the bilateral proximal subclavian artery was noted. Marked luminal narrowing was seen in the right tibial artery in a peripheral ultrasound. A subsequent CT angiogram (CTA) disclosed circumferential thickening of thoracic aorta, complete occlusion of bilateral common carotid arteries, and critical stenosis of bilateral proximal subclavian arteries ( Figure 4 ).\nBased on the patient's past history of TA, ocular symptoms, and relevant eye examinations, stage II TR was diagnosed according to the Umaya and Asayma classification. She was referred to a vascular surgeon and underwent balloon angioplasty of bilateral subclavian arteries. During the procedure, dilation of bilateral subclavian arteries was carried out with a 4 x 40 mm balloon through right femoral artery approach. Post-angioplasty angiogram showed markedly improved flow of pre-vertebral subclavian artery, predominately in the left side. She was put on prednisone (40 mg/day), CTX (50 mg/day), aspirin, and vasodilators afterward to induce remission in TA.\nOne month after surgery, the patient reported a slight improvement in her vision. Her blood pressure is 72/55 mmHg in the upper extremities. FFA revealed improved retinal blood flow, with a persistent number of microaneurysms and late-phase dye leakage in both eyes. Paralleled to FFA findings, OCTA showed considerably increased vascular density in the SCP ( Figures 3B, H ) and DCP layer ( Figures 3E, K ). She remained on tapered prednisone (35 mg/day), CTX (50 mg/day), vasodilator (40 mug twice daily), and aspirin.\nOn follow-up of 6 months, she continued to sustain good improvement in symptoms. Her BCVA improved to 0.6 in the right eye and remained stable at 0.4 in the left eye. IOP was 9 mmHg in both eyes. A fundus examination revealed a superficial hemorrhage in the peripheral retina of the left eye. Repeated FFA of the left eye showed a decrease of arm-to-retina circulation time and arteriovenous transit time to 16 and 8 s, respectively. The number of microaneurysms decreased, with less evident dye leakage in the midperipheral area. Right eye angiogram showed similar improvement ( Figure 5 ). No capillary non-perfusion and retinal neovascularization were observed. Notably, OCTA revealed further normalization of vascular density, along with restoration of perifoveal anastomotic capillary arcade ( Figures 3C, F, I, L ). CTA revealed moderate restoration of flow in the bilateral common carotid arteries and subclavian arteries.",
"gender": "Female"
}
] |
PMC8795594
|
[
{
"age": 12,
"case_id": "PMC9850095_01",
"case_text": "A 12-year-old boy with a one-year history of muscle weakness and gait disturbance that progressed slowly presented to our hospital. He had no remarkable past medical history or family history of metabolic bone disease. Roentgenographic examination revealed a deficiency of mineralization like that seen in rickets patients in the epiphysis of the bilateral proximal tibias and distal femurs ( Figure 1A ), and a radiolucent lesion with endosteal scalloping and marginal sclerosing in the left fibula ( Figure 1B ). Blood examination revealed a low serum phosphorus level of 2.3 mg/dL (reference range: 3.0-4.7 mg/dL), and a markedly high serum FGF23 level of 329 pg/mL (reference range: <50 pg/mL), and so we suspected PMT with TIO caused by the tumor-like lesion in the left fibula.\nWe resected the tumor en bloc by preserving the periosteum of the fibula after confirming its benignity by intraoperative frozen section diagnosis, and the cavity of the tumor was filled with beta-tricalcium phosphate (beta-TCP) ( Figure 1C and Supplemental Figure 1 ). The muscle weakness gradually improved, and the gait disturbance normalized within two months. In the postoperative 21-month follow-up, he had no symptoms, and hypophosphatemia was not detected. Roentgenographic examination revealed absorption of the beta-TCP and bone formation and union of the fibular shaft ( Figure 1D ).\nHistopathological examination of the resected tumor revealed irregularly deposited osteoid and osteoblast-like tumor cells scattered between the osteoid and reactive osteoclastic giant cells ( Figure 1E and Supplemental Figure 2 ). In immunohistochemistry, expression of FGF23 was shown in the cytoplasm of the osteoblast-like tumor cells ( Figure 1F ), CD56 was diffusely positive on the cell membrane of the tumor cells and SATB2 was diffusely positive on the tumor cells ( Supplemental Figure 2 ).\nAfter resecting the tumor, the serum FGF23 level started to decrease immediately and normalized within 3 hours ( Figure 1G ). It was also within the normal range five days after surgery. The increase in serum phosphorus level was slightly delayed as compared with that of the FGF23 level, and was observed 6 days after the operation ( Figure 1H ).\nWe performed RNA sequencing using a resected specimen from the patient and identified a novel in-frame fusion involving NIPBL (encoding Nipped-B gene product and fungal Scc2-type sister chromatid cohesion proteins) and BEND2 (encoding a protein which has two BEN domains in the C-terminus) ( Figure 2A ). The fusion protein contained the phosphorylation site derived from NIPBL and the BEN domain derived from BEND2 ( Figure 2B ). Whole-exome sequencing identified three point mutations (IFT172:NM_015662:exon3:c.A263G:p.N88S; VAF = 0.22, GAB2:NM_080491:exon6:c.A1409G:p.D470G; VAF = 0.15, and PRKCH : NM_006255:exon14:c.A1996T:p.I666F; VAF = 0.17), none of which\nwere reported as driver mutations. In polymerase chain reaction, the amplification of target regions containing breakpoint of the chromosomal structure was confirmed using two primer sets in tumor DNA of the PMT ( Supplemental Figure 3 ).\nWe cloned and transfected the NIPBL-BEND2 fusion gene to HEK293T and MG63 osteoblast lineage cell line. The NIPBL-BEND2 transfected cells showed faster proliferation at 48 hours after transfection (p = 0.001 and 0.003, Student's t-test, respectively). ( Figures 2C, D ). A gene set enrichment analysis of the fusion gene-introduced HEK293T cells identified a significant enrichment of MYC-target genes, consistent with faster proliferation ( Figure 2E ). However, the expression of FGF23 (log2 fold change; 0.031) and FGFR1 (log 2 fold change; 1.59) was not changed significantly by the transfection in addition to the KL/KLB, SPP1, SFRP4, and MEPE ( Supplemental Data 1 ), even though the tumor mRNA showed relatively high FPKM in these genes ( Supplemental Table 3 ).",
"gender": "Male"
}
] |
PMC9850095
|
[
{
"age": 15,
"case_id": "PMC4150428_01",
"case_text": "A 15-year-old male patient reported with the chief complaint of swelling on the left side of lower jaw since 9-10 months. He noticed a swelling in the lower jaw in the posterior region, which was initially small in size and gradually increased to the present size. It was initially painless, but the patient now complains of mild intermittent pain, occasionally. The patient was prescribed antibiotics and analgesics by a general practitioner 3-4 times in the last 9 months.\nExtraoral examination revealed a solitary swelling in the left mandibular ramus area. The swelling was roughly oval in shape with approximate size of 2 cm x 3 cm. The margins of the swelling were diffuse. The skin overlying the swelling was smooth and normal in color (Figure 1).\nOn palpation, temperature of overlying skin of swelling was slightly elevated. The consistency of the swelling was bony hard. Medio-lateral expansion of the cortical plates was noted at angle of mandible. A single left submandibular lymph node of size approximately 1 to 1.5 cm was noted, which was slightly tender and mobile.\nIntraoral examination revealed a single small swelling in retromolar area, slightly obliterating the pterygopalatine raphe. Expansion of buccal and lingual cortical plate was noted. A deep periodontal pocket was noted distal to 37 (Figure 2).\nProvisional diagnosis on clinical examination was made as benign odontogenic lesion. Differential diagnosis of ameloblastoma, odontogenic keratocyst, dentigerous cyst associated with 38, calcifying odontogenic cyst, calcifying epithelial odontogenic tumor, and ameloblastic fibroma was considered.\nRadiographic examination of the lesion showed a well-defined unilocular radiolucency involving the left side of the mandible which extended anteroposteriorly from the distal surface of the left mandibular second molar to the posterior border of ramus of mandible and superoinferiorly from coronoid notch to the inferior border of mandible. It showed well corticated borders. Resorption of the distal surface of root of the mandibular second molar was also noted (Figure 3).\nCT and 3D CT scan of the lesion showed a unilocular osteolytic lesion in the posterior part of body and ramus of the mandible. Bilateral cortical plate expansion was noted. Perforation of the lingual cortical plate was also revealed (Figures 4 and 5). Radiologic examination showed that mandibular left third molar was absent. So the possibility of \"dentigerous cyst associated with 38\" which was considered in the provisional diagnosis was ruled out.\nRoutine hemogram was performed and all the blood indices were within normal limits. An incisional biopsy was then performed, which on histopathologic examination revealed a cystic cavity lined by odontogenic epithelium and a connective tissue capsule. Epithelium shows palisaded basal layer resembling ameloblast-like cells and a superficial layer showing stellate reticulum-like cells. The connective tissue was dense, fibrous with collagen fibers arranged haphazardly. Numerous engorged and dilated blood vessels were seen (Figure 6).\nFrom the above clinicopathological features, a diagnosis of unicystic ameloblastoma was made. The patient then underwent a mandibular segmental resection involving condyle and reconstruction was done with 2.7 mm titanium reconstruction plate and iliac crest graft, under general anesthesia. Healing was uneventful. Patient was followed up after 1 month with radiographic evaluation which showed complete healing of wounds and well maintained graft (Figure 7).\nWe received a segmental resected specimen involving condyle, coronoid process, upto ascending ramus, which showed perforation in the anterior border of ascending ramus. Histopathological examination of the excisional biopsy specimen showed lesional tissue that consisted of a cystic cavity lined by odontogenic epithelium and connective tissue capsule. The epithelium showed cuboidal or columnar basal cells with hyperchromatic nuclei, nuclear palisading with polarization, cytoplasmic vacuolization with intercellular spacing, and subepithelial hyalinization and superficial layer showing stellate reticulum-like cells. There was also proliferation of these cells in cystic lumen in a plexiform pattern. The cells are arranged in interconnecting strands and cords with peripheral palisaded layer and central stellate reticulum-like cells (Figure 9). Tissue material resembling an odontogenic keratocyst lining was not observed, even with serial sections of tissue. So possibility of ameloblastic transformation of odontogenic keratocyst was also excluded.\nAccording to the classification suggested by Ackermann et al., it was classified as unicystic ameloblastoma subgroup 1.2 which is also known as plexiform unicystic ameloblastoma.",
"gender": "Male"
}
] |
PMC4150428
|
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