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pmc-6381751-1	A 66-year old male of Spanish origin, known for Crohn disease and type I bipolar affective disorder for at least 15 years, was brought to the emergency department for sudden mutism that developed within 2 h. In the emergency room, the patient was described catatonic, presenting with no speech at all, staring, stupor, immobility and rigidity of the four extremities and a trismus. He was not vomiting. Standardized scale for catatonia was not used on admission. Retroactively, according to the psychiatrist in charge of the initial evaluation of the patient, the score on Bush-Francis catatonia scale would have been 8. The patient was diaphoretic, with obvious dysautonomic signs: blood pressure was 175/126 mmHg, heart rate was 105 bpm and respiratory frequency was 22/min. His temperature was 36.7 °C. Laboratory results showed a mild hyponatremia (Na+ 132 mmol/l, N: 136–144), the glomerular filtration rate was 95 ml/min and liver tests were as follow: ASAT 33 U/l (N: 14–50), ALAT 30 U/l (N: 12–50), alkaline phosphatase 61 U/l (N: 25–102), γGT 62 U/l (N: 9–40). Creatine kinase (CK) blood concentration was 56 U/l (N: 47–222) and arterial gasometry was in the normal ranges. Hematology was unremarkable, namely leucocytes were 4.9 G/L, with 79% neutrophils. A brain CT excluded an ischemic stroke and a cerebral hemorrhage. A 24 h-EEG was unremarkable. Clozapine blood level at admission was not determined. While reviewing the patient history, it appeared that he was hospitalized in a psychiatric ward until 2 months ago for a manic episode, which has required many drug treatment trials because of adverse effects or treatment failure. These were namely, a three-fold CK elevation related to olanzapine, mild leucopenia and agranulocytosis related to aripiprazole, extrapyramidal manifestations on haloperidol and high dose quetiapine lack of efficacy. Facing this resistant episode a try with clozapine was then made. The patient was eventually discharged, stabilized on clozapine 50 mg daily, with 12.5 mg on demand, valproic acid 500 mg twice daily and his usual treatment for Crohn disease (mesalazine 1000 mg, azathioprine 50 mg twice daily). For an unknown reason, clozapine was then abruptly stopped and replaced by risperidone 5 mg daily associated with quetiapine 200 mg daily three days before the emergency admission. Besides valproid acid was decreased to 300 mg daily. Therefore, the hypothesis of a cholinergic rebound syndrome was evoked, with a potential contribution of risperidone overdose in the catatonic manifestation. Risperidone and quetiapine were stopped and biperidene 2.5 mg intravenously was administrated leading to a dramatic recovering of the patient’s ability to speak within minutes after application. Other manifestations (nausea, sweating, tachycardia, hypertension) took few days to recover on clozapine 50 mg and daily oral administration of 2.5 mg of biperiden. The patient was eventually discharged twenty days after admission with only mild bradykinesia and gait instability. His mental state was stable during the whole hospital stay.
pmc-6382443-1	The proband is a 14-year-old boy who was born at term to non-consanguineous parents following a normal pregnancy. The patient had sucking difficulties during the neonatal period. At the age of 3 months, he suffered from seizures and at 6 months, he was found to be hypotonic. He presented global developmental delay: He sat unsupported at 12 months, walked independently at 27 months, and speaks only three words. Dentition was delayed. At 2 years old, neurological examination detected severe intellectual disability, ataxia of gait, receptive and non-verbal communication skills higher than verbal ones and frequent drooling. He presented an abnormal electroencephalogram (EEG), although it was not the characteristic found in AS patients. The behavioral phenotype included happy demeanor, easily excitable personality, hyperactivity, attention deficit, stereotypies, attraction to water, aggressiveness, and autistic features. A clinical suspicion of AS was raised which was not confirmed molecularly. AS testing included methylation PCR of the 15q11.2-q13 region, UBE3A sequencing, and UBE3A MLPA analysis (SALSA MLPA P336-A2, MRC Holland, Amsterdam, The Netherlands). In addition, subtelomeric MLPA (SALSA MLPA P070), Autism MLPA (SALSA MLPA P343-C1) and 60K array-based comparative genomic hybridization (aCGH) were performed with normal results.
pmc-6382493-1	A 2-month-old boy, who was otherwise healthy, was referred to our center for bilateral leukocoria. Retrolental fibrovascular tissue with hemorrhage was found in his right eye. His left eye had a shallow anterior chamber, a corneal opacity, and was progressing toward buphthalmia (Figure ). Ocular B-scan showed a closed funnel retinal detachment in both eyes. Genetic testing revealed a homozygous NDP mutation (c.376T>C), confirming FEVR. His mother was heterozygous for the mutation. The reported mutation resulted in an amino acid change at codon C126R. This mutation affects cysteine residues responsible for creating the cysteine knot formation, leading to disturbed norrin folding and stability. ND was diagnosed based on the clinical and genetic findings. Ophthalmic examination of the patient's parents was unremarkable, but FFA revealed slight peripheral vascular leakage in the mother. The mother became pregnant again at 32 years of age and underwent amniocentesis 18 weeks into the pregnancy. No fetal mutations were identified. An ultrasound of the fetus's eyes was also performed at 30 weeks gestational age. Coronal sections showed symmetrical globes, transparent and bright lenses, and clear vitreous cavities. The mother delivered a 3.2-kg infant at 40 weeks gestational age. Postnatal fundus evaluations were normal in both eyes.
pmc-6382493-2	A 4-month-old boy was referred to our center following a routine examination. Fundus examination revealed bilateral retinal folds (Figure ), along with heavy exudation in the right eye, making him an FEVR suspect. Vision was normal in both parents, and ophthalmologic examination revealed normal anterior segments. Both parents also underwent FFA. The father's results were normal, but the mother had an avascular periphery in both eyes (Figure ). Genetic testing identified a novel FZD4 frameshift mutation (c.1010dupA) in both the patient and the mother, confirming the FEVR diagnosis. Disease staging revealed stage 4B and 4A FEVR in the right and left eyes of the proband, respectively, and stage 1 FEVR in both eyes of the mother. The mother became pregnant for the second time when she was 34 years old and was offered prenatal counseling because the baby had a 50% chance of inheriting the FEVR mutation. An amniocentesis performed at 19 weeks of gestation and revealed that the fetus did carry the FZD4 mutation (c.1010dupA). The parents decided to continue the pregnancy, and a detailed fetal ultrasound scan was performed at 32 weeks of gestation. No ocular abnormalities were observed. The baby girl was born full-term at a weight of 3,300 g. Postnatal FFA did not reveal any leakage, but an avascular zone and an excessive, straightened vessel branching pattern was observed in both eyes. Therefore, the baby girl was diagnosed with stage 1 FEVR.
pmc-6382493-3	A 4-year-old boy was referred to our clinic for bilateral cataracts and poor vision. His parents reported that he had normal physical and mental development until 2 years of age. Since then, the boy began showing difficulties in learning and communicating with others. Oculo-digital sign and self-injury behaviors were also noted. Ocular B-scan ultrasonography revealed a retinal detachment in both eyes. The patient underwent pars plana vitrectomy and lensectomy in the left eye, and fundus photographs taken after surgery showed a partially attached retina (Figure ). The patient's father was healthy, except for physical disabilities related to poliomyelitis. Ophthalmic examination revealed no abnormalities. The mother had phthisis bulbi and keratopathy in the left eye with a visual acuity of no light perception. In the right eye, she had a dragged disk and a visual acuity of 20/125. Genetic testing identified a homozygous deletion of exons 2 and 3 in the NDP in the patient. His mother and maternal aunt were both carriers of the deletion. As a result, the proband was diagnosed with ND. Even though the mother was a manifesting ND carrier, the aunt had a normal fundus examination in both eyes. Prenatal counseling was offered to the couple when the mother became pregnant again because the odds of passing the identified mutation to the child were 50%. Because ND is an X-linked mutation, a baby boy with the mutation would develop ND. However, a baby girl with same mutation may or may not be a manifesting carrier. The mother underwent amniocentesis at a gestational age of 19 weeks, and genetic analyses revealed that the female fetus had the same NDP mutation. The pregnancy was continued, and ultrasound examination at 31 weeks gestational age revealed no abnormalities. A healthy, full-term baby girl was born with normal fundi (Figure ).
pmc-6382915-1	A 75-year-old man with no medical history presented with dysphagia. Upper gastrointestinal endoscopy revealed type III esophageal cancer in the middle thoracic esophagus and type II gastric cancer in the cardia. Computed tomography (CT) showed a left renal tumor and multiple swollen lymph nodes in the neck, mediastinum, and abdomen, including the left renal hilar and para-aortic regions. Thus, he was diagnosed with multiple primary cancers of the esophagus (T3N3M0), stomach (T2N1M0), and kidney (T1bN1M0) according to the Union for International Cancer Control (UICC) 7th edition. He received two cycles of neoadjuvant chemotherapy with nedaplatin and 5-fluorouracil followed by a two-stage operation to decrease the surgical stress. The first-stage operation involved preoperative percutaneous endoscopic gastrostomy tube placement followed by thoracoscopic subtotal esophagectomy in the prone position and cervical esophagostomy placement with mediastinal and cervical lymphadenectomy. The operation was uneventful; it involved 29 mL of blood loss and took 284 min to complete. Gastrostomy feeding was started on postoperative day (POD) 3 with a polymeric formula (ENSURE H®; 700 mOsm/kg) at a rate of 20 mL/h for 15 h per day, which was increased to 40, 60, and 80 mL/h for 15 h per day on POD 5, 6, and 7, respectively. The postoperative course was uneventful, although the patient developed diarrhea followed by acute abdominal pain and distension with bloody drainage through the gastrostomy tube on POD 7. On examination, he was febrile at 37.2 °C, but the rest of his vital signs were normal. His abdomen was distended with mild diffuse tenderness without guarding or rigidity. Laboratory evaluation revealed an elevated white blood cell count and C-reactive protein level of 11.9 × 109/L and 59.0 mg/L, respectively. Arterial blood gas analysis showed no signs of metabolic acidosis. Dynamic CT showed massive hepatic portal venous gas extending to the superior mesenteric vein, a dilated gastrointestinal tract with pneumatosis intestinalis, segmental poor enhancement of the bowel wall, and small amounts of ascites (Fig. a, b). Angiography showed diffuse spasms in the branches of the superior mesenteric artery and poor splanchnic blood flow with no signs of mesenteric arterial thrombosis (Fig. ). Under a diagnosis of NOMI, we started intra-arterial infusion of papaverine, prostaglandin E1, and heparin through the angiography catheter with intravenous infusion of antibiotics. His symptoms gradually improved, and a CT scan on POD 8 showed a significant reduction of hepatic portal venous gas (Fig. c). Gastrostomy feeding was restarted on POD 21, and he was discharged on POD 48. Two months after the first-stage operation, he underwent partial gastrectomy and reconstruction with a gastric tube without nephrectomy or abdominal lymph node dissection because of his poor general condition. He died of systemic metastasis 9 months after the first operation.
pmc-6382915-2	A 68-year-old man with diabetes and atrial fibrillation presented with dysphagia. His medical history was significant for pylorus-preserving gastrectomy for gastric cancer and small bowel resection for trauma. Upper gastrointestinal endoscopy revealed type II esophageal cancer in the lower thoracic esophagus. CT showed multiple swollen lymph nodes in the neck, mediastinum, and abdomen. Thus, he was diagnosed with esophageal cancer (T3N3M0) according to the UICC 7th edition. He underwent three cycles of neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil followed by thoracoscopic subtotal esophagectomy in the prone position, open total gastrectomy, colonic reconstruction, and jejunostomy tube placement with three-field lymphadenectomy. During the operation, adhesiolysis for abdominal severe adhesions caused by previous operations was difficult. The blood loss volume and operation time were 448 mL and 510 min, respectively. Jejunostomy feeding was started on POD 3 with a polymeric formula (Racol® NF; 400 mOsm/kg) at a rate of 20 mL/h for 15 h per day, which was increased to 40 and 60 mL/h for 15 h per day on POD 4 and 6, respectively. The postoperative course was uneventful, although he developed persistent diarrhea and cervical anastomotic leakage on POD 7. The anastomotic leakage improved with conservative treatment, although he developed severe diarrhea followed by acute abdominal pain and distension with bloody drainage through the jejunostomy tube on POD 9. On examination, his vital signs were normal, and his abdomen was distended with mild diffuse tenderness without guarding or rigidity. Laboratory evaluation revealed an elevated white blood cell count and C-reactive protein level of 14.3 × 109/L and 26.0 mg/L, respectively. Arterial blood gas analysis showed no signs of metabolic acidosis. Dynamic CT showed the same findings as in case 1. Under a diagnosis of NOMI, we started intravenous infusion of papaverine, prostaglandin E1, and antibiotics. His symptoms gradually improved, and a CT scan on POD 10 showed a significant reduction of hepatic portal venous gas. He started oral intake on POD 21 and was discharged on POD 28. He was alive without recurrence 9 months after the operation.
pmc-6382916-1	A 32-year-old woman presented at the ophthalmology clinic with chief complaints of floater and painless gradual decreased visual acuity in her right eye from 5 days earlier. There was no previous history of ocular surgery, trauma, systemic disease, and medication. There was a medical history of ESWL for a 12-mm right renal pelvis stone 1 week prior to her presentation. Pre- and post-operative urine culture was negative, and urine analysis was normal. In clinical examination, best-corrected visual acuity (BCVA) of the right eye decreased to line 20/40 of the Snellen chart. Left eye BCVA was 20/20. Intraocular pressure of both eyes was 15 mm/Hg. Right eye slit-lamp examination revealed conjunctival injection and + 1 cell in the anterior chamber. Also, fundus examination showed clear media with + 3 vitritis and an elevated white ball-like lesion with 1 disc diameter size, on para-fovea with fluffy border. The right eye macular optical coherence tomography (OCT) displayed a hyper-reflective lesion in the vitreomacular interface (Fig. ). There was no remarkable sign in the examination of the left eye. Diagnostic vitreous tap was performed, and the sample was sent for smear and culture. The smear of the vitreous sample with Giemsa stain showed multiple fungal spores with budding yeast and fungal pseudo-hypha and leukocyte infiltration (Fig. ). Cultures of the vitreous sample after 7 days were positive for Candida albicans. The patient was admitted to the hospital; then, intravitreal injection of amphotericin-B (5 μg/0.5 ml) was performed and topical atropine 1% Q6hr, topical prednisolone acetate 1% Q4hr, topical ciprofloxacin 0.3% Q6hr, intravenous amphotericin-B 1 mg/kg/day, and oral fluconazole 100 mg Q12hr were started. Systemic workup including ANA, ANCA (P, C), AMA, VDRL, FT-ABS, Toxoplasma IgM and IgG, HBs Ag, HBc Ab, HCV Ab, HIV Ab, serology for Borrelia and Bartonella, Mantoux and interferon-γ test were all negative. Erythrocyte sedimentation rate, C-reactive protein, CBC and platelet, fasting blood glucose, AST and ALT, BUN, creatinine, ACE, IgG, IgM, and IgA level were within the normal limit. Peripheral blood smear, para-nasal sinus, and chest X-ray were normal. After 72 h of treatment, BCVA improves to line 20/30 of the Snellen chart. The lesion size became smaller, and borders became clear and sharp. The patient was discharged, and treatment continued with oral fluconazole 100 mg Q12. After 6 weeks of initial treatment, the right eye BCVA was 20/20. The infiltrative lesion completely disappeared in fundus examination but a trace of vitritis was apparent. No signs of scar formation and traction of the retina were observable. The macular OCT revealed mild cellular debris in the site of the primary lesion (Fig. ). There was no recurrence in a 2-year follow-up.
pmc-6383168-1	A 62 year old gentleman came to the surgical out patient with complaints of abdominal discomfort, occasional left sided abdominal pain for the past 15 days. He had decreased appetite, projectile vomiting, no dyspepsia, no history of fever and bowel habits were normal. On examination, a large mass of 10 × 8 cm was palpated in the left hypochondrium, left lumbar, and umblical region. It was mobile, not moving with respiration and firm in consistency. On palpation of neck, the thyroid gland was found to be enlarged with palpable right lobe. Upper and lower gastrointestinal endoscopy was normal. Contrast enhanced computed tomography (cect) abdomen showed large lobulated, heterogenously enhancing mass with internal necrosis and calcifications in the left hypochondrium in the region of distal body and tail of pancreas (). There were no other foci of metastasis in abdomen or chest. Chest X-ray of patient was normal. Ultrasound of neck revealed a suspicious nodule in right lobe of thyroid measuring 1*1 cm with no nodal enlargement. Pre-operative ultrasound guided biopsy showed features suggested of poorly differentiated malignancy (that was negative for gastro intestinal stromal tumor markers). His CEA and Ca 19-9 were normal. Fine needle aspiration cytology of thyroid nodule was done under image guidance which was suggestive of papillary carcinoma thyroid. As image guided biopsy of abdominal tumour could not be done patient was planned for laparotomy. At laparotomy, patient was found to have a bilobed tumor arising from the lesser sac adherent to the pancreas and abutting the stomach, transverse colon, and left adrenal and splenic hilum (). The tumor was resected en bloc (distal pancreatectomy and splenectomy). The post operative period for the patient was uneventful. Oral feed started on 3rdpost operative day drain tube was removed on 5thpost operative day. Patient was discharged on the 12thpost operative day. The histopathology showed the presence of very irregularly shaped cells with nuclei that exhibited a “wavy, buckled appearance”. Multiple sections studied showed pancreatic tissue with adjacent fairly circumscribed neoplasm composed of spindle cells arranged in sheets and fascicles. Pancreatic margin appeared free from tumour. There are areas showing alveolar and glandular patterns.There are areas showing hyalinization, necrosis and fibrosis. Tissue organization shows great variability, with hypocellular myxoid areas and areas of major cellularity diagnostic of Malignant peripheral nerve sheath tumour (MPNST). The histologic changes of MPNST include spindle cells with comma-shaped nuclei, tactoid bodies, nuclear palisading, hyaline bands, and schwannoma-like and curlicue foci ().The tumour showed focal S100 positivity,was strongly positive for ki67, was positive for vimentin ( and 5) and negative for cytokeratin,synaptophysin and all GIST markers(CD 117,DOG 1,PDGF) We re-examined the patient thoroughly and there were no cutaneous markers for neurofibromatosis and examination of the eye was normal. Patient was reviewed after a period of 2 months. Positron emission tomography () was done which revealed para aortic nodes and 2 mesentric nodes. It also revealed a metabolically active nodule in thyroid with cervical nodal metastasis. Patient was taken up for total thyroidectomy with functional neck dissection. Histopathology confirmed papillary carcinoma of thyroid with positive lymph nodes. Patient was advised to undergo a radioactive iodine scan which showed 0.3% uptake. Hence patient was started on chemotherapy for para aortic nodes with a regimen of paclitaxel, adriamycin, ifosumide and mesma. Patient has completed 3 cycles till date and is on regular follow up.
pmc-6383214-1	A Mongolian male, aged 19 years, resident of a hilly district of Nepal, presented to our outpatient department with chief complaints of pain and swelling in both hands and feet for 6 years. The pain was insidious in onset, throbbing in nature and not relieved by over-the-counter medications. The patient also complained of profuse sweating, progressive enlargement of hands and feet, and gradual coarsening of facial features. His family history was significant for consanguinity – his grandparents have a consanguineous relationship. There was otherwise no history of a similar illness in the family members, and this was the first time the patient sought medical attention for this issue. There was no history of scalp dandruff or rashes, and the patient denied having symptoms such as fatigue, eye redness, eye or mouth dryness, chest pain, or exertional dyspnea. There was no history of fever, palpitations, heat intolerance, or tremors. The patient was hemodynamically stable, alert, and conversant when he presented. On examination, there were marked skin folds in his forehead, face, and eyelids (Fig. ). Clubbing and swelling of bilateral knee joints and ankle joints were also evident (Fig. ). Cardiovascular, respiratory, neurological, and thyroid examination performed for the patient was otherwise unremarkable. There was no scalp dandruff, rashes, psoriatic nail changes, subcutaneous nodules, or eye redness noted on examination. We performed biochemical investigations including a full blood count (total lymphocyte count 9.5 × 109/L, hemoglobin 12.4 mg/dL, platelet 410 × 109/L), liver function test (normal), and renal panel (normal). Thyroid function test, rheumatoid factor, and anti-cyclic citrullinated peptide were normal. As there was a suspicion of acromegaly, we investigated the levels of insulin-like growth factor-1 and performed an oral glucose tolerance test; the results of both of these tests were normal. Radiography of the skull showed mild cortical and subperiosteal thickening (Fig. ). Bilateral knee x-rays revealed symmetrical, irregular, and periosteal hypertrophy with subperiosteal new bone formation in the proximal tibia and fibula and distal femur (Fig. ). Radiographs of bilateral ankles demonstrated irregular subperiosteal new bone formation and cortical thickening of distal tibia, fibula, calcaneum, and talus (Fig. ). The x-rays of bilateral hands showed soft tissue tumefaction, particularly in the distal phalanges and periostitis and hyperostosis of metacarpal and proximal phalanges (Fig. ). Aspiration of synovial fluid from knee joint was done to rule out other forms of arthritis. Synovial fluid analysis proved it to be non-inflammatory, non-hemorrhagic, and non-septic. The patient stayed in our center for 6 days and was managed with selective COX-2 inhibitors (Eltrocoxib 60 mg PO, OD), steroids (Prednisolone 5 mg PO, OD), oral retinoids (20 mg morning and 10 mg HS), and retinoid ointment. The joint pain and swelling improved markedly with treatment. He was subsequently discharged with outpatient follow-up scheduled 1 and 6 months later, respectively. However, the patient has since returned to his hometown and missed his physical appointments. Follow-up was established via telephone on both occasions, and it was found that his joint pain and swelling was minimal and the pachyderma had reduced gradually since discharge. The patient experienced no relapses or complications from the condition or the medications.
pmc-6383265-1	A 40-year-old female patient had been diagnosed as classical Mantle cell lymphoma (MCL) at stage IV B with deletion of TP53 gene by lymph node biopsy in local hospital at September, 2017. The immumohistochemical staining results were as follows: CD20(+), PAX5(+), CD79a(+/−), CD5(+), CD21(+), CD23(+), CycIin-D1(+), Ki-67(30%), CD43(mild+), BCL-2(+), BCL-6(+), SOX11(partial +), and molecules including CD2, CD3, CD7, CD10, TIA1, GrB and TdT were negative. EBV was undetectable by in situ hybridization. She had received first and second line chemotherapy including R-CHOP, R-DHAP and R-VCOP, but had progressive disease. Only the combination of ibrutinib and rituximab (IR) resulted in a transient partial remission. In March 2018, she came to our hospital for CAR T cell therapy, a clinical trial of sequential infusion of CART19 (or CART20) and CART22 expressing murine scFv of anti-CD19, anti-CD20 and anti-CD22 in combination with CD28 and 4-1BB costimulatory domains, and CD3ζ signaling domain ( number ChiCTR-OPN- 16008526; ChiCTR1800019385 and ChiCTR1800019449). When she was admitted to our hospital, she had a fever, severe dyspnea, and hypoxemia with the lowest SpO2 of 80%. Systemic edema, superficial lymphadenopathy and splenomegaly (reaching her pelvic cavity) were found by physical examination. The lymph nodes were about 3 cm in diameter, like beads-on-string. The number of leukocytes was 71.9710^9/L in the peripheral blood, and the level of serum lactate dehydrogenase (LDH) was elevated (up to 1619 U/L). Follow-up FDG-PET/CT (Positron Emission Tomography-Computed Tomography) showed swollen lymph nodes throughout the body with increased metabolism, the maximum standard uptake value was 5.7. The maximum standard uptake value of splenomegaly was 6.2. The bone metabolism was hyperactive, and the maximum standard uptake value was 7.5. Furthermore, the lungs and bilateral adrenal were also infiltrated by lymphoma (max Deauville score 5) (Fig. a). 66 and 63% of lymphoblasts could be found in the peripheral blood and bone marrow smear, respectively. Her complex karyotype was 43, X, −X, − 9,-10,t(11;14)(q13;q32), del(13)(q12q22). A deletion of exon 7 of TP53 gene that induces frameshift (c.756delC,p.R253Pfs92), and a nonsense mutation of the exon 34 of NOTCH2 gene (c.7242C > A, p.Y2414;C.7176 T > G,p.Y2392) were found by next-generation sequencing (NGS). The patient was high risk evaluated by MIPI. In view of the patient’ s poor clinical status, we removed the excess tumor cells by apheresis and isolated primary T lymphocytes from peripheral blood to urgently prepare anti-CD19 chimeric antigen receptor T cells (CART19) and anti-CD22 chimeric antigen receptor T cells (CART22). The patient was conditioned with VP-16 100 mg and ifosfamide 1 g were used alternately, combined with rituximab 375 mg/m2 every week together with ibrutinib 560 mg daily to halt the tumor progression (Fig. a). The line chart showed that rituximab had a transient tumor-cytotoxic effect. About 20 days later, the patient’s general condition improved. Edema of her face and lower limbs had appreciably diminished with shrank splenomegaly to the horizontal of the umbilicus. Then, she received lympho-depleting chemotherapy with fludarabine (25 mg/m2 on day-5~ − 3) without cyclophosphamide, as she had been treated with IFO before. Autologous CART22 (1.210^7 cells/kg) was infused on day 0 and day + 1, followed by CART19 (710^6 cells/kg) on day + 2 and day + 3 (Fig. b). The autologous CAR T cells proliferated in vitro and the tumor-cytotoxic effect of CART22 and CART19 was up to 99.34 and 99.01% at an effector/target ratio of 25:1 with 65.1 and 32.4% infection efficiency, respectively (Fig. c). At the first day of infusion, the WBC declined to 1.0810^9/L with 0.1310^9/L neutrophile granulocytes, 0.5910^9/L lymphocytes and 0.310^9/L monocytes. She only had a mild fever and 1 grade cytokine-release syndrome (CRS), manifested as mild elevated interleukin-6 and unchanged ferritin (Fig. d and e). On day + 7 after autologous CAR T cell therapy, the disease significantly progressed, as the white blood cell count increased sharply, reaching 63.6110^9/L on day + 9 in the peripheral blood, along with enhanced LDH up to 959 U/L. Despite this, the CART22 cell product was infused again on day + 7 and day + 8, which did not alter the disease progression (Fig. b). Moderate edema of her face and both lower limbs reappeared, and the enlarged spleen reached pelvic cavity again. These indicated that autologous CAR T cell therapy failed to halt the disease progression in spite of increased number of CAR T cells and copies of CART19 and CART22 in the blood at 2 weeks after first CAR T cell fusion (Fig. f and g). At this time (day + 14) the ratio of CD4+/CD8+ T cells, including CAR T cells, in the peripheral blood was 3.7, a significant rise over the normal expected ratio (Fig. h). The detail of the process of treatment before and after autogenous CAR T cell therapy and her responses was summerized in Additional file : Table S2. In the presence of relapsing disease, we tried to repeat the therapy using haplo-identical T cells derived from the patients’ daughter transfected with the anti-CD20 and anti-CD22 CAR constructs to generate haplo-identical CART20 and CART22 cells respectively. Before haplo-CAR T cell therapy, we pre-conditioned the patient with rituximab and ibrutinib, combined with BCL-2 inhibitor venetoclax. The efficacy of rituximab was transient although the addition of venetoclax resulted in a significant drop in the white cell count (Fig. a). Subsequently she was conditioned with a standard lympho-depleting chemotherapy regimen consisting of fludarabine (25 mg/m2) and cyclophosphamide (20 mg/kg) on day − 4 ~ − 2 (Fig. b). This was associated with a further reduction in the size of her spleen and a drop in her peripheral WBC to 0.710^9/L with 0.6310^9/L neutrophile granulocytes, 0.0410^9/L lymphocytes and 0.0210^9/L monocytes (Fig. b). Again, the haplo-CART cells could proliferate in vitro and the tumor-cytotoxic effect of CART22 and CART20 was up to 89.41 and 96.55% at an effector/target ratio of 25:1 with 49.7 and 71.2% infection efficiencies, respectively (Fig. c). The infusion of haplo-CAR T cells was performed as follows: 8.510^6 cells/kg of CART22, divided into three infusions on day 0 ~ + 2, followed by 610^6 cells/kg CART20, divided into two infusions on day + 2 and day + 3. On day + 10 after haplo-CAR T cell infusion, the WBC increased to 1.6710^9/L with 0.0610^9/L neutrophile granulocytes, and 1.4210^9/L lymphocytes and 0.1510^9/L monocytes (Fig. b). She had a persistent high temperature (maximum 39.4 °C) from day + 4 to day + 10, accompanied with obvious chest distress and facial swelling. Her plasma IL-6 concentration was 48.7 times higher than its base level, its peak reached 1314 pg/mL at day 6, and ferritin was 19.4 times higher and its peak reached 9474 μg/L at day + 10 (Fig. d and e), suggesting that this was a cytokine release syndrome rather than a reaction to her haplo-identical T cells. At day + 6 methylprednisolone was used to control her inflammatory reaction. Her NT-proBNP reached 8020 pg/mL and continuous renal replacement therapy was required to support her during this period. After 7 days of high fever, the patient’s general condition improved. Physical examination revealed that superficial lymph nodes had shrunk, and the spleen was palpable only 3 cm below the left costal margin. The ultrasonography indicated several splenic infarctions about 2 cm in diameter and the spleen pachydiameter was 5.4 cm. CAR T cell number and the copies of CART22 and CART20 increased dramatically and reached the peak at the second week (Fig. f and g). This detection time was 11 days from the last infusion of haplo-CAR T cells on day + 3. In addition, the ratio of CD4+/CD8+ T cell in the peripheral blood was significantly lower (0.4) than normal (proportional inversion) on +day 14 after haplo-CAR T cell infusion (Fig. h). At this time point, we were unable to detect the presence of minimal residual disease by flow cytometry and quantitative-PCR in the bone marrow. One month later, evaluation of haplo-CAR T-therapy revealed that the disease was in sustained remission. FDG-PET/CT on day + 45 was unable to detect any significant disease (max Deauville score 4), and the infiltration of tumor cells into lungs vanished (Fig. a and b). We next assessed the presence of minimal residual disease using next generation sequencing to monitor circulating tumor DNA. We were able to detect the presence of p.Thr253Profs92 mutation in the TP53 gene but this had significantly reduced to a near undetectable level (Fig. c). Ten days after haplo-CART cell infusion, she began to be treated with ibrutinib and venetoclax again as a maintenance therapy, as a bridge to a formal haplo-identical HSCT from her daughter. The detail of the process of treatment before and after haplo-indentical CAR T cell therapy and her responses was summerized in Additional file : Table S3.
pmc-6383272-1	A 50-year-old homeless Caucasian man with history of AIDS presented for generalized weakness and productive cough with clear-yellow sputum without hemoptysis for 1 month. He also endorsed fevers, chills and rigors for 1 week and a 15 pound unintentional weight loss in 1 month. AIDS was diagnosed over 20 years ago and has been noncompliant with various combinations antiretroviral therapy (cART) regimens including emtricitabine/tenofovir, abacavir/lamivudine, darunavir, and ritonavir. Patient was lost to follow-up for 2 years until he was recently incarcerated and released from jail. Patient was born in Ohio but moved to California at 2 years of age, and had remote military service in Georgia in his early 20’s. Otherwise the patient never left California thereafter. He has never explored caves or been in contact with birds, bats or its excrements. Patient’s initial temperature was 38.5° Celsius and he was also tachycardic. Physical exam revealed a disheveled, cachectic male with temporal muscle wasting, no respiratory distress on room air, and was otherwise unremarkable. Laboratories revealed a white blood cell count of 3.7 TH/uL, absolute lymphocyte count of 185, absolute CD4 count of 20 cells/uL, and HIV viral load of 181,000 copies/mL. Comprehensive metabolic panel was within normal ranges except for a low albumin (2.8 g/dL). Lactate dehydrogenase (277 u/L), ferritin (1343 ng/mL), erythrocyte sedimentation rate (111 mm/hr), and C-reactive protein (9.58 mg/dL) were elevated. Computed tomography (CT) of the chest with contrast revealed bilateral nodular opacities, the largest measured (3.6 × 2.2 cm), a left upper lobe mass with cavitation, right basilar (2.0 × 1.5 cm) nodule, mediastinal lymphadenopathy, ground-glass changes, and enlarged periaortic lymph nodes (Fig. a). CT abdomen and pelvis revealed retroperitoneal lymphadenopathy and was otherwise unremarkable. The initial workup included a lumbar puncture which was unremarkable. Multiple sputum acid fast bacilli (AFB) smears were negative. Interestingly, serum and urine were positive for rare AFBs using fluorochrome staining but nucleic acid amplification testing (NAAT) for Mycobacterium tuberculosis complex were negative, raising suspicion for disseminated nontuberculous mycobacterial (NTM) infection. Patient was started on treatment for presumed disseminated NTM infection with daily regimen of azithromycin/rifabutin/ethambutol with resolution of fever. However, patient still endorsed a cough. He subsequently underwent image guided fine needle aspiration of peripheral lung nodules. Pathology (Fig. b & c) revealed granulomatous inflammation with abundant Histoplasma capsulatum organisms by Grocott-Gomori’s methenamine silver stain (GMS) staining. There were no AFB positive organisms seen. Of note, the diagnosis was further supported by positive urine Histoplasma antigen (> 19 ng/ml) and serum Histoplasma antigen above the limit of quantification. Histoplasma antibody with mycelial antigen was < 1:8. Blood and final bronchoscopy cultures eventually grew H. capsulatum weeks later. Once diagnosis of H. capsulatum was made, in addition to NTM treatment regimen, the patient was also started on intravenous amphotericin B lipid suspension at 5 mg/kg for 2 weeks and subsequently discharged with itraconazole. Patient was also started on cART (emtricitabine/tenofovir/dolutegravir) prior to discharge. With treatment, all constitutional symptoms and laboratory abnormalities improved. He was subsequently discharged home with close outpatient follow-up.
pmc-6383305-1	A 59-year-old man underwent video-assisted thoracic surgery of the left upper lobe with ND2a-1 lymphadenectomy 4 years prior to disease presentation and was diagnosed as having stage IA (T1bN0M0) adenosquamous carcinoma of the lung (Fig. A–C) harbouring EGFR exon 19 deletion based on the American Joint Committee on Cancer staging system, seventh edition. He was a non-smoker with no previous medical problems. Two years after the surgery, he was diagnosed as having recurrence in the mediastinal lymph nodes and left anterior chest wall. Erlotinib (150 mg once daily) and bevacizumab (15 mg/kg every 3 weeks) were started as first-line therapy. After 19 months of the therapy, the lung cancer also metastasized to the right supraclavicular lymph node. He underwent percutaneous supraclavicular lymph node needle biopsy as the first-repeat biopsy. Adenosquamous carcinoma harbouring EGFR exon 19 deletion and T790M mutation was detected. Osimertinib (80 mg once daily) was started, and the patient achieved partial response. Seven months after starting treatment with osimertinib, the mediastinal lymphadenopathy recurred, and multiple new liver metastases were seen. The second-repeat biopsy for the subcarinal mediastinal lymph nodes was performed. The histological diagnosis was SCLC harbouring EGFR exon 19 deletion without T790M mutation (Fig. D–F). He was treated with combination chemotherapy of cisplatin (80 mg/m2, day 1, every 3 weeks) and etoposide (100 mg/m2, days 1–3, every 3 weeks). After one cycle of chemotherapy, computed tomography (CT) imaging demonstrated that the mediastinal lymph nodes had shrunk, but the hepatic metastases had disseminated. Fine-needle aspiration biopsy of the liver was performed, and the histological diagnosis was also SCLC harbouring EGFR exon 19 deletion without T790M mutation (Fig. G–I). After four cycles of chemotherapy, the size of the mediastinal lymph nodes further decreased, but the hepatic metastases increased. Two months later, liver metastases became worse, and new lesions of the bone metastases at spine developed. We administered amrubicin (35 mg/m2, 75% on days 1–3, every 3 weeks) for the next treatment. However, the treatment was changed to irinotecan (100 mg/m2, 75% on day 1, 8, and 15 every 4 weeks) after one cycle of amrubicin because of elevated liver enzymes and pancytopenia. After two cycles of irinotecan, he developed superior vena cava syndrome, which was treated with radiotherapy. He was died 13 months after diagnosis of transformation to SCLC. An autopsy was performed, and microscopic examination showed metastases to lungs, mediastinum, cervical lymph nodes, liver, left kidney, right adrenal gland, bones, and epicardium. Microscopic examination demonstrated tumour heterogeneity of various organs. Although histological types of most metastatic lesions were SCLC or LCNEC, adenocarcinoma was found in the left kidney, coexistence of adenosquamous carcinoma and SCLC was observed in mediastinum, and adenocarcinoma and SCLC were found in right adrenal gland and cervical lymph nodes (Fig. ). LCNEC of epicardium also showed EGFR exon 19 deletion without T790M mutation.
pmc-6383397-1	A 21-year-old female patient came to our service with a complaint of unilateral right-onset headache associated with diplopia initiated 6 months earlier. She had no personal or family remarkable antecedents. She never smoked. Six months earlier, the patient started to experience one-sided right throbbing headache. She denied nausea, vomiting, or photo- or phonophobia. Fifteen days after the pain onset, she noticed double vision and medial deviation of the right eye, which forced her to wear an eyepiece to perform her activities and drive. She went to several centers and used various medications such as paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and triptans without improvement. Three months earlier, she started using dexamethasone 4 mg daily with partial pain control but maintenance of diplopia. At the examination, the patient had cushingoid face, violaceous striae, and right VI cranial nerve palsy with no other neurological changes. Blood tests were normal (). A contrast-enhanced MRI scan of the brain did not show any remarkable features (). A spinal tap released crystalline cerebrospinal fluid (CSF) with an opening pressure of 14 cm of water. Biochemical, microbiological, and cytological analyses of the CSF were normal (). CT scan of thorax did not show any evidence of lymphoma or sarcoidosis. Prednisone 1mg / kg was then started. With one week of treatment, complete reversal of ocular paralysis and remission of pain were observed. However, when the corticoid was gradually withdrawn, the patient returned to pain and returned to paralysis of the VI right pair. The prednisone was increased again to 1 mg / kg this time with reversion of ocular paralysis but without pain control. Several prophylaxis attempts were made with beta-blockers, calcium channel blockers, topiramate, and tricyclics without any symptomatic control that would allow corticosteroid withdrawal. The pregabalin 150mg daily was then introduced. With 7 days of medication onset there was already an important remission of pain. With 15 days of pregabalin initiation, the retitration of prednisone was started without any intercurrence and the patient reversed the exogenous Cushing syndrome. Pregabalin was maintained for one year and retracted. Currently, the patient has been free of pain for 2 years.
pmc-6383399-1	An 11-year-old boy visited our outpatient clinic with complaints of persistent right cheek pain. His family history revealed that his father had severe hearing impairment. His medical history showed that he had allergic rhinitis and chronic sinusitis that had been treated until 3 months previously by an otolaryngologist. The patient initially visited our outpatient clinic with complaints of high fever, sore throat, and comorbid right cheek pain and mild swelling 6 weeks previously. A checkup at a dental clinic performed on the day before this initial visit revealed no abnormal findings. He showed clinical symptoms of streptococcal pharyngitis. A rapid antigen test for group A streptococcal infection showed positive results. The patient was diagnosed with streptococcal infection. Facial cellulitis was also suspected and treatment with amoxicillin helped improve symptoms. However, facial pain recurred within 4 weeks of the initial visit. The patient had mild tenderness and swelling of the right cheek. Head computed tomography revealed mild mucous membrane swelling and effusion in both sinuses ( left). Because recurrence of cellulitis with sinusitis was suspected, cefditoren pivoxil treatment was initiated. However, because the pain persisted, he visited our department. Physical examination revealed no abnormal findings except right cheek tenderness in the area that corresponded with the region supplied by the second branch of the trigeminal nerve (the maximally nerve). Although marked tenderness was evident, no point with hyperalgesia, where a light touch elicited severe pain, was observed. No facial paralysis or oral disorders were observed. Blood examination revealed no abnormal findings. Recurrence of sinusitis was suspected. Based on the physical examination and laboratory tests, the patient was clinically diagnosed with TN. Subsequently, oral clarithromycin administration was initiated for sinusitis that might have caused or exacerbated TN. However, administration of clarithromycin for 1 week was not effective for his facial pain. Brain magnetic resonance imaging (MRI) revealed no neurovascular compression ( right), which ruled out idiopathic, classical TN. During this time, we interviewed the patient on the nature of the right cheek pain. The patient described the pain as persistent, nagging, and dull in nature, which was completely different from the characteristics of pain associated with TN. Furthermore, trigger maneuvers failed to evoke pain. These evaluations excluded TN, and, thus, PIFP was diagnosed in week 2. Low dose of oral anticonvulsant carbamazepine (50 mg, twice a day) was initiated but was ceased due to general fatigue after the first administration. Although the patient had been previously cheerful and greeted us when entering the examination room, he became gradually emotionless with headache and nausea in week 5. In addition, feeding difficulties and numbness in the arms occurred. An orthostatic tolerance test revealed no positive findings for orthostatic dysregulation. It became difficult for the patient to attend school in week 6. Because various somatic symptoms developed in addition to PIFP, psychological factors were suspected to be pertinent in the etiology of PIFP. During a detailed medical interview with the patient and his mother, several problems were revealed: the patient loved swimming but his swimming record had plateaued after fixing his swimming form even though he practiced vigorously at a top-class swimming club team. Moreover, because of a recent finger injury, he could not practice as intensely as he wanted; therefore, his competitive ability as a swimmer deteriorated. Furthermore, in early adolescence, the patient had difficulties in communication and his relationship with his father was strained due to the father's hearing impairment. Because these suggested that the circumstances surrounding him might have led to somatoform disorders, psychological counseling was ordered in week 6. As the patient faced, understood, and tolerated his psychological stress through counseling and psychotherapy twice a week, he gradually became expressive, worked up his appetite, and could attend school in week 10. Although sinusitis recurred at week 29, no facial pain developed. The patient received psychological counseling twice or thrice a month by this time. After 8 months, the frequency of counseling was reduced to once in 2 months. During this period, the patient's voice changed and became deeper at puberty. After confirming that facial pain as well as general malaise did not occur, even when the patient experienced distressing events, such as terminal examinations, counseling was ceased after 1 year and 8 months. After 3 years, the patient went on to high school and currently attends school cheerfully without any complaints and has resumed swimming.
pmc-6383417-1	The patient (31 years old, male) presented with body weakness, anorexia, and headache at the surgical emergency service department. The patient was febrile (axillary body temperature, 37.9°C) and had a heart rate of 98 beats/min. He was tachypnoeic with a respiratory rate of 40/min and normal blood pressure of 110/70 mmHg. The patient had initially presented two months earlier with a history of unproductive cough that was of insidious onset, and cough was intermittent in nature. He had fever, malaise, and difficulty with breathing. There was no orthopnoea, paroxysmal nocturnal dyspnoea, or a history of contact with persons with a chronic cough. Later, the patient observed that there was difficulty in breathing soon after the onset of a cough that worsened with moderate activities such as climbing a staircase and also a significant weight loss. On further clinical examination, the chest was asymmetrical, with reduced chest expansion and tactile fremitus on the left lung field. There was stony dullness to percussion and reduced vocal resonance over the same area. There was also reduced air entry in the left lung field. Other systems were essentially within the normal limit. Chest radiograph showed a massive left pleural effusion and deviation of the trachea to the right. Ultrasonography scan showed a massive left-sided pleural effusion with lung abscess. The differential diagnoses were lobar pneumonia complicated by pleural effusion. The patient had a closed thoracotomy tube drainage with an initial drainage of 600 ml of pus. A Ziehl–Neelsen staining of the pleural effusion showed no acid-fast bacilli, and the final diagnosis was empyema thoracis. The hematogram and the clinical chemistry laboratory results are shown in . The microbiological culture of the pus from the pleural empyema showed a culture of C. violaceum on Columbia blood agar and MacConkey agar. C. violaceum was oxidase positive, indole negative, utilized citrate, catalase positive, and fermented malonate. C. violaceum was susceptible to ciprofloxacin, gentamicin, amoxicillin/clavulanic acid, and imipenem. Resistance was detected against ceftazidime, cefuroxime, and cotrimoxazole. He was treated empirically with intravenous amoxycillin-clavulanic acid and ceftriaxone for seventy-two hours. Due to poor patient response, once we had the sensitivity result from the microbiology examination. He was switched to intravenous ciprofloxacin 200 mg 12 hourly for one week and was discharged after clinical cure. He was treated for one week with intravenous ciprofloxacin as an inpatient.
pmc-6383417-2	An infant (two months old, male) was admitted to the paediatric unit of the hospital on account of fever, convulsion, and vomiting. There was no other significant past medical history prior to presentation. The family history indicates that the family lives in an one-room apartment with a borehole as the sole source of water. The two-month-old baby was exclusively breastfed as per the national policy on breastfeeding of babies in the first 6 months of life. The urine stream was normal, and the flow was adequate. There was no posterior urethral valve: this would have been discovered in the first week of life before discharge from the hospital after birth since all the male infants are always examined before discharge. The convulsion in this patient is unlikely to be a febrile convulsion; unfortunately, EEG was not done which would have been helpful in differentiating between seizures and abnormal movements. Clinical examination showed no abnormality (axillary temperature, 36.7°C, heart rate: 152 beats/min, respiratory rate: 22/min, weight: 5.8 kg; an electrocardiogram carried out was also normal). But occipitofrontal circumference is 44.4 cm, and this is macrocephaly which should have been investigated further. Other physical examinations were within the normal limits. Clinical Laboratory investigation findings are as given in . CSF culture did not show bacterial growth. A clean-catch, amber-coloured urine was collected, nonturbid with a pH of 6.5, and had a specific gravity of 1.005; all other urine parameters such as leukocyte and protein were negative. Urine culture yielded the growth of C. violaceum (5.5 × 108 CFU/ml). The antibiotic susceptibility testing showed sensitivity to ofloxacin, ciprofloxacin, nitrofurantoin, amoxicillin/clavulanic acid, cefuroxime, ceftazidime, imipenem, and gentamicin. The final diagnosis was urinary tract infection. The patient was treated with intravenous cefotaxime (275 mg, bd for 7 days) and was later discharged after clinical cure, as part of the national guidelines; the child initially received intramuscular artemether (Paluther®) until malaria was ruled out.
pmc-6383417-3	A child (5 years old, male) was admitted at the children ward of the hospital on account of fever and generalised oedema, and no sign of malnutrition was noticed. The patient was not in daily contact with farmland or stagnant water, and there was no history of any skin lesion or a sore throat prior to his admission to the hospital. The oedema was initially periorbital before becoming generalised. The parents did not observe any deviation in the frequency of passage of urine but the urine was frothy in nature. Clinical examination revealed a febrile child (38°C), not pale, with a body weight of 18 kg (45th percentile), and a height of 112 cm (67th percentile) []. The pulse rate was 96 beats/min, the blood pressure was 84/50 mmHg, and laboratory investigations results are given in . The clean-catch urine was amber coloured with a pH of 6.0 and specific gravity of 1.020. The urine was positive for protein (++), leukocytes (++), and ketones (+) with only traces of blood (ACON Laboratories, San Diego, USA). The 24-hour urinary protein was 1.99 g/24 hours (normal range: <100 mg/24 hours) with a urine volume of 410 ml. Urine microscopy indicated pus cell of 3-4 cells per high power field. Urine culture yielded growth of C. violaceum (5.8 × 108 CFU/ml), which was susceptible to ofloxacin, ciprofloxacin, gentamicin, nitrofurantoin, and imipenem and resistant to amoxicillin/clavulanic acid, ceftazidime, cefuroxime, and cotrimoxazole. The patient received intravenous ceftriaxone (500 mg, 12 hourly, for 7 days) until the temperature became normal; furosemide (iv) dose of 40 mg 8 hourly for the first 24 hours was later reduced to 20 mg 8 hourly for four days and then switched to oral furosemide at a dose of 20 mg tds for 3 days with spironolactone (po, 12.5 mg bd for 7 days). Spironolactone is used to give the additive potassium ion-sparing effect. The patient's symptoms regressed with treatment. The patient received two pints of blood due to anemia. The final diagnosis was urinary tract infection, and the patient was discharged home after clinical improvement for follow-up two weeks later. The quick recovery of this patient and the normal urinalysis at the hospital follow-up visits were not in conformity with nephrotic syndromes (differential diagnosis). The fact that the symptoms regressed without dialysis and no relapse on follow-up are enough to rule out chronic renal failure.
pmc-6383419-1	We report a 52-year-old gentleman, asymptomatic, and nonsmoker, without comorbidities but with class II obesity BMI of 37.7. He was referred from the lung cancer screening program as the high-resolution chest computed tomography (CT) scan delineated a 1.5 cm mixed ground glass opacity (GGO) with a larger solid component in the right middle lobe (RML) (). This nodule increased in size at the follow-up CT scan; therefore we decided to resect the middle lobe anatomically using subcostal access. The patient was given general anesthesia with double lumen endotracheal intubation and placed in a lateral decubitus position (dorsal decubitus 40 degrees) (). A 5 cm oblique incision parallel to the costal arch was made. Then the subcutaneous tissue and rectus abdominis were dissected along the subcostal margin; xiphoid process and pericardiophrenic fatty tissue were detached. A subcostal tunnel was bluntly dissected using finger until the mediastinal pleura was opened at the cardiophrenic angle. Lastly, covidien wound protector (WPLGR914) was placed (). A thoracoscopic lens with a 30° angle (Olympus, Melville, NY) was used and interlobar fissure was examined. Lobectomy was performed as in the video [subcostal right middle lobe lobectomy video] (). Systematic mediastinal lymph nodes dissection includes stations 2,4 right paratracheal, 9,10,11,12 and subcarinal lymph nodes. Long and sturdier VATS instruments were used. Also, curved tip stapler technology aids to allow passage around the vascular structures (). We did not put any extra ports and the operative time was 30 minutes. After completing the procedure, a 28 F chest tube () was inserted through the same subcostal wound. The patient was given routine venous thromboembolism prophylaxis (6000 i.u UFH) 12 hours after operation. No postoperative arrhythmia or air leak was detected. The patient was discharged on the third postoperative day with an uneventful recovery (). Postoperative pain score (Wong-Baker FACES) on 1, 2, 3,7,15 days was evaluated. It was (4-2-0-0-0) consecutively. During the follow-up, no incisional hernia was detected. The pathology results delineated a (1x 0.8) cm invasive infiltrating adenocarcinoma [80% ductal/20% papillary] without lymphovascular, neural, or pleural invasion (T1aN0M0), stage I A1 according to the non-small-cell lung carcinoma (NCCN) guidelines version 4.2018-8th edition]. Five lymph nodes were harvested, and all were negative for metastasis (0/5).
pmc-6383422-1	This is a 60-year-old right-handed man with past medical history of relapsing-remitting multiple sclerosis diagnosed 20 years ago with prior beta interferon treatment for 8 years and with chronic left residual hemiparesis who presented to the emergency room after experiencing generalized weakness followed by a fall to the ground with apparent loss of consciousness. While the patient reported no loss of consciousness, he did not have memory of the events surrounding the fall. EMS was called and patient was airlifted to the nearest percutaneous intervention-capable center after the ECG showed a ST segment elevation in the leads V1 to V3, so the ST segment elevation myocardial infarction (STEMI) alert was activated. In the emergency department, the patient was without chest pain. Upon further questioning, he denied any family history of heart disease including no cardiomyopathy, heart failure, arrhythmias, or premature or sudden cardiac death. Vitals demonstrated mild tachycardia to 105 beats per minute and a temperature of 38 degrees Celsius, and labs revealed a negative troponin level. Ultimately, the ST segment elevation myocardial infarction (STEMI) alert was cancelled due to the high clinical suspicion of the type 1 Brugada pattern in a syncopal patient with anteroseptal ST elevations without chest pain. Workup for the febrile episode revealed positive serology for influenza B. Oseltamivir was started and the patient completed 5 days of treatment. The patient was no longer febrile and his tachycardia had resolved, but he continued to show a persistent type 1 Brugada pattern on the ECG during the entire hospitalization course as seen below (). The patient subsequently went for a transthoracic echocardiogram which demonstrated a normal left and right ventricular function and no structural abnormalities. He also underwent coronary angiography, which revealed nonobstructive coronary artery disease. Ultimately, the primary concern was to elucidate, whether the patient's initial clinical presentation represented an episode of arrhythmogenic syncope induced by the underlying Brugada syndrome, as this would lead to a recommendation for implantation of a cardiac defibrillator. Electrophysiology service was consulted and felt that the mechanism of his fall was mechanical and not related to a true syncopal event. They recommended an outpatient follow-up for consideration of an event monitor or loop recorder.
pmc-6383425-1	In 2016, a 39-year-old healthy woman began having night sweats, and within the next month, she discovered an erythematous, round skin lesion in her left, middle forearm. She presented to her primary care provider with a progressively growing erythematous nodule and was treated with antibiotics (). While the initial lesion continued to grow, a second lesion appeared next to the first (). The patient was evaluated by a dermatologist, and two biopsies were obtained. The patient was diagnosed with DLBCL non-GC subtype (Figures –). CT showed left axillary lymphadenopathy with lymphoma confined to the left forearm. Bone marrow biopsy showed no lymphoma. PET scan showed lymphoma in the left forearm and left axilla. The patient began R-CHOP regimen on April 2017. Following three cycles of R-CHOP, the tumor continued to grow (). In addition to the R-CHOP regimen, radiotherapy to the left forearm begun in May 2017. After the fifth R-CHOP cycle and radiotherapy completion, the tumor began to shrink (). Unfortunately, one month later, the patient noted a nodule on her left upper arm (). Two more cycles of R-CHOP were administered. In the next month, restaging PET/CT showed an increase in nodularity of the left forearm, indicating progressive lymphoma. Fine-needle aspiration (FNA) of the left forearm lesion was positive for DLBCL non-GC subtype. The R-CHOP regimen was stopped, and the patient received one cycle of E-SHAP (etoposide, methylprednisolone, and cytarabine). Skin masses and nodules in her left upper arm continued to grow fast within 3 months (). The regimen was changed to rituximab, gemcitabine, and oxaliplatin with no response. The patient was evaluated by the bone marrow transplant team at the Methodist hospital and was referred to MD Anderson Cancer Center (MDACC) to participate in a chimeric antigenic receptor (CAR) T-cell clinical trial. Lymph node (left axilla) needle biopsy at MDACC was diagnostic for DLBCL non-GC subtype immunophenotype. The neoplasm showed a diffuse pattern composed predominantly of large cells with immunoblastic cytological features. Immunohistochemical studies were reviewed, and the neoplastic cells were positive for CD19, CD20, PAX-5, BCL2, BCL6, and MUM-1/IRF4. Ki-67 showed a proliferation rate of 70–80%, negative for Epstein–Barr virus-encoded small RNA (EBER). Immunohistochemistry using c-MYC antibody showed 70–80% of neoplastic cells weakly to moderately positive for MYC. Combined with the BCL2 result, the neoplasm was a double expressor immunophenotype (). MYC FISH analysis showed a positive result for MYC gene rearrangement. IGH BCL2 FISH was negative for IGH/BCL-2 gene rearrangement. BCL6 FISH was positive for BCL6 gene rearrangement with 70% of the interphase indicating BCL6 rearrangement. Although the patient's stem cells were collected in November 2017 and only CD4 cells were amplified, she did not receive the infusion. She developed Bell's palsy of the right side of her face that was attributed to a viral illness for which she received treatment. She also developed double vision. Lumbar puncture showed atypical lymphoid cells, consistent with involvement by patient's lymphoma. CSF analysis by flow cytometry was positive for large number of aberrant B cells with partial CD10 expression. Aberrant cell phenotype was positive for CD10, CD19, CD20, and CD22. At the beginning of December, the left upper arm mass had continued to grow (). She received high-dose methotrexate. Days later, a third nodule was present in the patient's left forearm (). At the end of the month, she was admitted to MDACC ER, was unable to walk, and had generalized weakness. Brain MRI showed no acute intracranial abnormality or intracranial metastasis. Lumbar puncture CSF showed large malignant cells, consistent with involvement by the patient's known DLBCL. Cervical, thoracic, and lumbar MRI showed C5 metastasis that extended into the right C4-C5 and C5-C6 foramina. No spinal cord compression was observed. Days later, lumbar puncture CSF showed large malignant lymphoid cells, morphologically consistent with involvement by patient's known DLBCL. CSF flow cytometry was positive for lymphoma with aberrant cell phenotype positive for CD19, CD20, CD22, CD38, CD43, CD79b, and CD200. Cervical, thoracic, and lumbar MRI showed an enhancing mass involving the right C5 vertebral body with extension into the right C4-C5 foramina (Figures and ) and epidural extension of tumor along the right aspect of the spinal canal touching the right aspect of the cord and leptomeningeal metastasis (). She received Ferreri regimen (high dose of methotrexate with high-dose cytarabine) followed by intrathecal methotrexate. Lumbar puncture CSF showed rare atypical cells, suspicious for involvement by patient's known large B-cell lymphoma. The patient was told that was terminal and advised to seek comfort measures. She decided to continue treatment and radiotherapy to the left arm, 3000 cGy for 10 cycles. After beginning left arm radiotherapy, she received craniospinal radiation 2000 cGy for 4 cycles. She began to walk again, and at the time, her left forearm tumor had subsided. Lumbar puncture CSF in the middle of January showed no malignant cells. In February 2018, the patient had a left upper arm mass infection, treated with IV antibiotics, and the left arm tumor mass was excised (). She received a skin graft from her left thigh (). Biopsy showed no evidence of lymphoma. A month later, CSF showed revealed no lymphoma. PET/CT, skull base to midthigh, showed soft nodular recurrence in the patient's left arm, as well as asymmetric uptake in the patient's right shoulder musculature. She was reevaluated by MDACC in order to continue her involvement in CAR T-cell clinical trial. The patient had regained the ability to walk, and talk without limitation, but had a residual left facial droop. Tumor status was as assessed as complete remission by PET; external CSF reports are negative for lymphoma. After evaluation, it was confirmed that she was in remission. In May 2018, CSF revealed no lymphoma. Bone marrow biopsy showed no blasts or lymphoma, and it showed hypocellular 35–40% marrow with active progressive trilineage hematopoiesis. Her left forearm and left upper arm skin had healed (). She received consolidation therapy with autologous bone marrow transplant, with conditioning regimen of rituximab, thiotepa, and carmustine. The patient was engrafted by day 12 and had a readmission shortly for C. diff diarrhea which was treated appropriately. The patient was subsequently discharged and is followed as an outpatient.
pmc-6383896-1	A was 52-years-old white woman with history of hypertension, diabetes, rheumatoid arthritis treated with corticoid (prednisone 10mg/day) was evaluated in our department with complains of recurrent infections and maxillary bone exposure. The patient reported that from 2007 started treatment for osteoporosis with zoledronic acid (5mg/month) that was replaced after five years by oral alendronate sodium (70mg / week). In 2013 underwent multiple exodontias and after 10 months developed persistent pain, recurrent infections and bone exposure at the sites of extractions. The patient was treated with multiple antibiotics and curettage by her general dental practitioner. In 2016, after worsening of the condition, she was referred to the Department of Oral and Maxillofacial Surgery of Universitary Hospital (Federal University of Paraiba, Brazil). The clinical examination revealed edema and erythema in the third middle of the face, total maxillary edentulism, presence of necrotic bone exposure involving an extensive area of the maxilla associated with dehiscence in the alveolar and palatine mucosa on the left side and minor points on the right side (Fig. A,B) which was notorious for its fetid odor and spontaneous purulent drainage. A CT-scan revealed necrotic bone widen throughout all maxilla and the left pterygoid process extending the proximity of skull base. A three-dimensional reconstruction view allowed clear visualization of the separation line at the Le Fort I level (Fig. C,D). The initial management included treatment for infection and the acute pain. The patient was given Amoxicillin 500mg plus Clavulanic Acid 125mg and Paracetamol 500mg as well as mouthwash (chlorhexidine digluconate 0.12%). Subsequently, due to the extent of osteonecrosis, total maxillectomy and removal of all adjacent necrotic bone were planned. Bone resection was guided by ultraviolet light fluorescence through the use of 100mg doxycycline twice daily for 10 days prior to surgery (Fig. A-C). In the immediate postoperative period, the patient was fed by nasal enteral tube to avoid food residues at the surgery site. In addition, smeared gauze with antibiotic ointment (bacitracin and neomycin) changed daily in the first seven days was utilized. Antibiotic therapy was maintained until 10 days after surgery and treatment with Tocopherol (500 mg, twice a day) and Pentoxifylline (400 mg, twice a day) was started aiming at reducing fibrosis and stimulating local vascularization for a period of eight months. After a period of Six-months, complete tissue healing was observed (Fig. D,E) Postoperative CT-scan performed six-months after the first surgery revealed satisfactory healing of the remaining bone (Fig. F,G) and then closure of the oro-antral communications left by bone resection was realized, as there was not sufficient tissue for primary closure. Closing was performed in three layers (Fig. A). The first layer consisted of the surrounding oral mucosa to form the floor of the maxillary sinus, followed by a layer of the buccal fat pad as pedicled graft and covered as a tunneling myomucosal flap from the buccinator muscle (Fig. B-F). Currently, the patient is without pain nor signs of relapse.
pmc-6383900-1	A 49 year-old female patient originally from Maghreb was referred to our Department due to some abnormalities found on a magnetic resonance imaging (MRI) developed for temporomandibular joint dysfunction. The patient had undergone radiotherapy for a NPC 11 years before. MRI revealed a cystic mass located in the clivus area (Fig. a,b). Contrast computed tomography scan (CT) showed a well-defined mass with low attenuation and unenhanced by contrast agents, located in the sphenoid bone (Fig. c,d). Nasal endoscopic examination showed a cystic mass in the upper side of the cavum. The patient had gone to the Emergency Unit complaining about visual disturbances some weeks before. Under general anaesthesia marsupialisation of the mucocele was performed, and a thick yellowish mucopurulent fluid was aspired from the mass (Fig. ). Pathological findings of the lining mucosa showed a mucous retention cyst with no evidence of tumor cells (Fig. ). Intraoperative cultures were sterile. Visual symptoms disappeared after surgery. The patient had regular follow-ups with no evidence of recurrence during 4 years. Informed consent was obtained by the patient.
pmc-6384032-1	A thin (41 kg) 85-year-old female presented with a 10-hour history of severe RUQ pain, nausea and vomiting. Her background included multiple lower abdominal laparotomies for gynaecological procedures, hypertension and dyslipidaemia. There were no clinical features of systemic upset. Her examination revealed a tender and guarded RUQ. Liver function tests were normal, white cell count was mildly elevated. Ultrasound demonstrated a distended gallbladder, without cholelithiasis and an asymmetrical gallbladder wall thickening to 8.5 mm. CT scan confirmed the diagnosis of acalculous cholecystitis, V-shaped superior portion of the gallbladder, low and horizontal lying gallbladder with hypoattenuation of the gallbladder wall compared with surrounding visceral structures (Figures -). After 24 hours of observation whilst on broad-spectrum antibiotics and simultaneous fluid resuscitation, the patient failed to clinically improve. The decision was made to undergo laparoscopic cholecystectomy. Intra-operative findings revealed a large, necrotic, completely torted and floating gallbladder. Its only attachment appeared to be the cystic duct and cystic artery on which the gallbladder had twisted 360 degrees in an anti-clockwise direction (Figures -). Principles of the operation include derotation then cholecystectomy and intra-operative cholangiogram. To establish the required critical view, it was necessary to unravel the torted pedicle before proceeding with the dissection. The cholecystectomy was otherwise routine. Gallbladder was retrieved in an endoscopic specimen retrieval bag and decompressed in the bag to allow delivery of the specimen and prevent spillage of bile intra-abdominally. Our patient’s discharge was delayed by an asymptomatic demand-related cardiac ischaemia, requiring 24-hour period of observation. She was discharged day two post-operatively with a plan for cardiology follow-up. Histology showed acute gangrenous cholecystitis.
pmc-6384033-1	The first patient was an asymptomatic male aged 59 years with a history of peripheral and autonomic neuropathy. Findings compatible with PMP were discovered in routine radiologic follow-up. Computed tomography (CT) demonstrated mucin material covering the omentum and extending in both paracolic gutters and the pelvis (Figure ). Serum carcinoembryonic antigen (CEA) was 210 ng/ml (normal value (nv) <5 ng/ml), while cancer antigen 19-9 (CA 19-9) was within normal range. A CT-guided biopsy was performed, which revealed mucin-producing cells of low dysplasia within mucin pools. Immunochemistry markers cytokeratin 20 (CK 20), CEA, and homeobox protein CDX-2 were positive while cytokeratin 7 was negative.
pmc-6384033-2	The second patient was a 62-year-old male who presented with a chief complaint of bowel movement disorders for over a year. On clinical examination, a subcutaneous, non-tender umbilical nodule was noted with no cough impulse, as can be seen in Figure . A CT scan demonstrated a cystic mass in the right lower quadrant with an unclear correlation to the appendix along with an ascitic collection of the right hypochondrium and paracolic gutter with septae (Figure ). Cytology of the ascitic fluid revealed acellular mucin without malignant component. Serum tumor markers CEA and CA 19-9 were within normal values. Both patients underwent complete cytoreductive surgery (CRS) and HIPEC. During the second patient’s laparotomy, a ruptured cecum was discovered along with extensive mucinous ascites; therefore, he was subjected to right colectomy (Figure ). Next, HIPEC followed for 45 minutes using oxaliplatin in a dose of 460 mg/m2 combined with intravenous 5 fluorouracil (400 mg/m2) and leukovorin (20 mg/m2). The postoperative course was uncomplicated in both patients, and they were discharged on the tenth and seventh postoperative day, respectively. The pathology report revealed low-grade mucinous neoplasm of the appendix in the first patient and low grade with sites of high-grade dysplasia mucinous neoplasm of the appendix in the second patient. The classification of the specimens was according to the latest consensus by the Peritoneal Surface Oncology Group International (PSOGI) []. Both patients were free of disease in their second-year follow-up.
pmc-6384034-1	A 33-year-old gentleman presented to the emergency department describing substantial right knee pain and swelling following a rotational injury. Inspection indicated significant joint effusion and subsequent examination showed absence of straight leg raise on the affected side. Plain radiographic evaluation of the knee showed lateral displacement of the patella (Figure ) confirming the clinical suspicion of a patellofemoral dislocation. Attempted closed reduction in the emergency department was unsuccessful, with the patella irreducible due to both an appreciable mechanical block and limited patient tolerance despite sedation. An MRI was thus performed to both assess any potential obstruction to closed reduction as well as to definitively evaluate the associated soft-tissue injury prior to determining the need for subsequent surgical intervention. Radiological investigations displayed evidence of lateral patellar dislocation on plain radiograph (Figure ), as well as MRI features of traumatic patellar dislocation including patellar displacement, associated patellofemoral effusion, MPFL and medial patellar retinaculum tears and avulsed patellar cartilage (Figures -). Additional MRI assessment showed a raised sulcus angle (>140) (Figure ). In the context of failed closed reduction as well as confirmation of the diagnosis, associated soft-tissue injuries and presence of risk factors for recurrent dislocation, this patient subsequently proceeded to definitive surgical treatment in the form of MPFL repair, with excellent postoperative function and no further dislocation at 46 months postoperatively.
pmc-6384036-1	A 40-year-old Caucasian female presented to our facility with a five-day history of right-sided numbness. She was referred to us from a small area hospital with a concern for a mass following computed tomography (CT) of the head. The CT report showed a 2 x 1.5 cm hypodense lesion adjacent to the posterior left basal ganglia/lateral thalamus and deep white matter adjacent to the posterior left lateral ventricle (Figure ). She complained of numbness of the right side of her face, right arm and leg, and a fall a couple of days prior to presentation. There was no numbness or weakness of the left side. She also complained of a headache and initially thought that her symptoms were related to it. The patient did not report any recent weight loss, fever, chills, or any other associated symptoms. Her past medical history was significant for migraine headache, hypothyroidism, chronic obstructive pulmonary disease (COPD), and lumbar radiculopathy with a herniated disc. Her past surgical history was significant for an L5-S1 microdiscectomy in 2013. Additional pertinent history included the patient having smoked a pack of cigarettes a day for 22 years and having a family history significant for lung cancer. The patient was hypertensive and all other vitals were stable. Physical examination revealed multiple neurologic findings, including decreased sensation to light touch on the right side of her face with the sensation of the tongue being intact, and decreased sensation in the right upper arm and right lateral leg below the knee. Decreased strength in her right upper and lower extremity (3/5 diffusely) was noted. A cardiopulmonary examination was unremarkable. MRI with gadolinium enhancement demonstrated multiple ring-enhancing lesions in the right and left periatrial white matter, the subcortical area of the left parietal lobe, and left temporal lobe on fluid-attenuated inversion recovery (FLAIR), T1-weighted (T1W), and T2-weighted (T2W) images (Figure ). It was associated with varying degrees of central liquefactive necrosis and perilesional edema. This suggested a differential of metastatic, inflammatory, infectious, or demyelinating disease. Further workup for metastatic disease was initiated with modalities, including CT of the chest, abdomen, and pelvis without contrast, followed by a bone scan, and x-rays of all four extremities, which were all reported to be negative. After metastasis was ruled out, the primary focus was turned towards multiple sclerosis and infectious pathologies. Workup for infectious causes was initiated with cerebrospinal fluid (CSF) analysis for aerobes and anaerobes, toxoplasma, Cryptococcus, fungal, and human immunodeficiency virus (HIV) infections. All studies proved to be negative. CSF workup for multiple sclerosis displayed zero oligoclonal bands. CSF concentration of myelin basic protein was elevated with a value of 7.1 (0.0 - 0.12 ng/ml), in addition to cytology results revealing mature lymphocytes. CSF protein and antibody analysis yielded insignificant results and included a normal IgG index. A serum IgG of 564 (700 - 1,600 mg/dL) and a CSF IgG being 1.4 (0.0 - 8.6 mg/dL) were obtained and were unremarkable. This further directed the need for a biopsy of the left thalamic lesion. Histologic sections demonstrated a predominant macrophage infiltrate that was relatively demarcated from the surrounding white matter. The immunohistochemical stains performed at an advanced medical center demonstrated olig2 to label glia, which can be interpreted as promoted recovery. A myelin stain (e.g., Luxol fast blue) showed loss of myelin with relative preservation of the axons on neurofilament protein (sm31). Oncologic markers were negative. Findings were significant for a macrophage-rich lesion and suggestive of demyelinating disease. After ruling out infectious and malignant conditions, we ultimately determined this to be an unknown inflammatory condition with a strong suspicion of multiple sclerosis (MS) at the forefront of possible etiologies. The patient was started on an eight-day course of intravenous dexamethasone, 4 mg every six to eight hours. The course of intravenous dexamethasone was completed in the hospital, and the patient was discharged to rehab with a month of per os (p.o.) prednisone, 20 mg daily, followed by a taper. She was also referred to a specialized medical center for MS confirmation, where they were better able to confirm the diagnosis as complex tumefactive multiple sclerosis (oligoclonal band negative). As a result, the patient was started on interferon beta-1a which was taken three times per week via subcutaneous injection. The patient subsequently returned to our facility for a similar episode four months following the initial presentation but with the now confirmed diagnosis of TMS. This was assessed as a relapse due to noncompliance of weekly injections. On imaging, MRI showed a reduction in the mass-like lesions (Figure ), leading us to believe the patient was responding to treatment. The patient was monitored for two days and discharged to rehab on oral teriflunomide.
pmc-6384037-1	An 18-year-old female, married, presented with a history of low-grade fever, dizziness, and lethargy for three weeks. On examination, she was pale and her spleen was palpable. Her complete blood count revealed hemoglobin (Hb) of 11.2 gm/dI, total leukocyte count (TLC) of 52,300/mm3, and platelet count of 8000/mm3; her differential leukocyte count showed promyelocytes 79%. In Figure , the bone marrow aspiration showed blasts and abnormal promyelocytes 85%, and Auer rods were positive. The histochemical stain was positive for Sudan black, whereas erythropoiesis and myelopoiesis were depressed. The bone marrow trephine biopsy revealed sheets of blasts and abnormal promyelocytes consistent with acute promyelocytic leukemia (FAB AML M3 (French-American-British acute myeloid leukemia type 3)). Molecular genetics, including the polymerase chain reaction (PCR) for AML gene markers and PCR for FLT3 ITD (Fms like tyrosine kinase 3-internal tandem duplication) mutations, were negative. The TP53 gene mutation by fluorescence in situ hybridization (FISH) was negative. Immunophenotyping for acute leukemia was done, but the report was insufficient in its description. Cytogenetics showed that a culture of lymphocytes at 37oC failed to yield any growth. Promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) translocation by PCR was done, which was not detected. We gave induction chemotherapy (3+7 regimen). On Day 16, her complete blood count (CBC) showed improvement with hemoglobin (Hb) 11.4 gm/dI, white blood cell (WBC) 5,100/mm3, and platelet count 240,000/mm3. The bone trephine procedure was done on post-induction Day 28, in which the bone marrow aspirate showed tri-lineage hematopoiesis, with a prominent increase in erythroid precursors and an increase in mast cells that constituted around 7% of the total nucleated non-erythroid population. These mast cells were spindle-shaped with centric to eccentric nuclei with clumped chromatin and absent nucleoli. They were also present in aggregates with erythroid precursors and prominent in the spicules. Blast cells were less than 5%. Bone trephine (hematoxylin and eosin (H&E)) section showed overall cellularity of around 55% to 60%. Cellular areas exhibited tri-lineage hematopoiesis alternating with areas of dense aggregates/sheets of atypical/immature mast cells. Immunohistochemical stains of mast cell aggregates were CD117 positive. Toluidine blue in the mast cell aggregates was metachromatic positive. Overall, the post-induction bone marrow (BM)/trephine biopsy showed a clearance of blast cells and increased mastocytes, which was suggestive of systemic mastocytosis with an associated hematologic neoplasm (SM-AHN, systemic mastocytosis with associated acute myeloid leukemia (SM-AML)) according to the World Health Organization (WHO) 2016 classification of hematolymphoid neoplasms. But clinically, according to updated WHO diagnostic criteria for systemic mastocytosis 2017, we cannot confirm the diagnosis of SM-AHN, as the mast cells were 7% in our patient while the criteria are >25%, and investigations like KIT-D816V or other activating point mutations of KIT and serum tryptase levels were also not available in our country. We started consolidation chemotherapy of the patient with high-dose cytarabine.
pmc-6384038-1	A 43-year-old Caucasian female with a family history significant for colon cancer in paternal grandfather and uncle presented to the emergency department for a one-week history of generalized abdominal pain in association with nausea, unintentional weight loss of four pounds and shortness of breath. Initial blood work showed elevated liver enzymes and elevated total and direct bilirubin. Fecal occult blood test performed was positive. Computed tomography (CT) of abdomen/pelvis with contrast demonstrated ascites, retroperitoneal and periportal lymphadenopathy and hepatomegaly with extensive confluent masses in the liver parenchyma representing extensive metastatic disease. The scan was also noteworthy for dilated loops of small bowel, transverse colon distended and distal colon collapsed. Tumor marker, CA 19-9 was elevated. Core needle biopsy of liver exhibited poorly differentiated adenocarcinoma with immunohistochemical staining positive for CDX2 and CK20 (Figure ), while being negative for PAX-8, CK7, p40, and TTF-1 indicating lower gastrointestinal tract being the primary site of origin for this metastasis respectively. Colonoscopy was performed which showed a large 5 x 6 cm fungating and friable obstructing mass in the cecum, 90 cm from the anal verge. Biopsies were taken and, results showed intramuscular adenocarcinoma in a background of tubulovillous adenocarcinoma (Figure ). Right hemicolectomy with ileostomy was performed and resected specimen showed 4.7 cm high-grade (poorly differentiated) adenocarcinoma involving cecum and appendiceal orifice and perforating parietal peritoneum (Figure ). Pathological staging of this tumor was pT4a, N1b, M1a (AJCC 7th edition) with low probability of microsatellite instability (MSI) found on immunohistochemistry. Surprisingly, surgical pathology report from resected specimen also showed a distinct 1 cm well-differentiated NET in distal half of the appendix invading visceral peritoneum (Figure ) and staining positively for pancytokeratin and synaptophysin (Figure ) with low Ki-67 proliferation Index (1%). Pathological staging of this tumor was pT4, N0 (AJCC 7th edition). This patient’s blood chemistry was also significant for elevated calcium (16.5 mg/dl). Considering evidence-based association of hypercalcemia of malignancy by NET via production of parathyroid hormone-related peptide (PTHrp), further workup for hypercalcemia was performed. Surprisingly, PTHrP level was reported to be within fairly normal range (20 pg/ml) but parathyroid hormone (PTH) levels were found to be elevated (302 pg/ml). Ultrasound soft tissue neck showed parathyroid glands hyperplasia. 25-hydroxycholecalciferol level was at higher normal range 45 ng/ml. Patient's hypercalcemia was initially treated with intravenous fluid normal saline and calcitonin which resulted in decrement of serum calcium level to 11 mg/dl. Calcitonin was discontinued at that time. Couple of days later, calcium level went up again to 16 mg/dl. Calcitonin was added back into the medication regimen along with sensipar, pamidronate and lasix. The patient could not survive for further workup and later died from complications of the disease.
pmc-6384041-1	A 67-year-old female initially presented with cognitive decline over two weeks, accompanied by vomiting, hallucinations, and blurred vision. She had a history of breast cancer and a recent cruise to the Bahamas, during which she remained on the boat due to inclement weather. She was admitted at an outside hospital and became progressively less responsive. She then became unresponsive and was transferred to our facility for critical care and video EEG monitoring. An MRI demonstrated asymmetric, diffuse hyperintensity of the cortex and striatum on T2-FLAIR and DWI sequences (Figure ). Using the 2011 UCSF modified grading system, this case met criteria for “MRI definitely CJD.” Additional brain MRIs performed over the next three weeks showed rapidly progressive signal change on DWI. An EEG was performed demonstrating slowing in the theta frequency and generalized epileptiform discharges at a frequency of 1 Hz. Approximately one-half to two-thirds of patients with sporadic CJD demonstrate triphasic, biphasic, or mixed periodic sharp wave complexes at a rate of 1 Hz, typically at a later stage [, ]. Lumbar puncture testing of CSF yielded positive results of RT-QuiC, T-tau, and 14-3-3 protein. RT-QuiC has sensitivity and specificity of 87-91% and 98-100%, respectively []. The 14-3-3 and T-tau test combined have sensitivity and specificity of 79% and 99%, respectively []. The patient continued to deteriorate clinically and died two months after her symptoms began.
pmc-6384041-2	A 61-year-old female with history of type 2 diabetes mellitus, hypertension, and hypothyroidism, presented with persistent dizziness. A brain MRI demonstrated an acute right middle cerebral artery infarct affecting the right insular cortex and right corona radiata without any evidence of CJD (“MRI definitely not CJD”). The patient was discharged after appropriate treatment for stroke. Six weeks later she presented from home with increasing confusion, weakness, difficulty ambulating, and hallucinations. A brain MRI demonstrated very subtle restricted diffusion in the bilateral frontal cortices, basal ganglia and thalami, greater on the left (Figure ). This was interpreted as global hypoxic ischemia, and neurology started the patient on aspirin and Plavix. The patient was discharged to a nursing home. Using the 2011 UCSF modified grading system, the imaging met criteria for “MRI definitely CJD.” One month later she was readmitted for acutely decreased responsiveness overnight. She underwent an initial stroke workup, and a third MRI was performed demonstrating progressive DWI hyperintensity in the caudate nuclei, lentiform nuclei, thalami, hippocampi, dorsal brainstem, and frontal and insular cortices. CJD was suggested by MR imaging, so the patient underwent lumbar puncture. An EEG demonstrated overall background activity in the 4 to 5 Hz delta range. Lumbar puncture testing of CSF eventually yielded positive results of RT-QuiC, T-tau, and 14-3-3 protein. The patient never improved during her hospital stay and went into cardiopulmonary arrest approximately four weeks later. She was intubated and resuscitated. Shortly afterward, the decision was made to withdraw care, and the patient was transferred to hospice four months after the initial presentation.
pmc-6384041-3	A 76-year-old male with history of prostate cancer initially presented to a primary care physician with slowly progressive confusion and memory loss. An MRI was obtained within our hospital network, which demonstrated asymmetric restricted diffusion involving the bilateral cortex and striatum with notable involvement of the precuneus (Figure ). CJD was suggested as the top differential diagnosis in the radiology report, and the patient was sent to our facility for admission and additional evaluation. Using the 2011 UCSF modified grading system, the imaging met criteria for “MRI definitely CJD.” An EEG was normal. A lumbar puncture was performed, and the patient was discharged to follow up as an outpatient. The initial CSF studies showed a positive RT-QuIC but negative T-tau and 14-3-3 protein results. Two months after the initial presentation, the patient went to UCSF, and the diagnosis of CJD was confirmed. The patient was treated with Niagen and Hismanal (astemizole). Six months after the initial diagnosis, the patient was reported to have intermittent confusion, gait disturbance, and occasional bladder and bowel incontinence. At this time he began receiving home hospice services (nine months after initial presentation). One year after the initial presentation, the patient had lost 40 lbs in the last six months, was nearly unresponsive, and unable to ambulate.
pmc-6384041-4	A 72-year-old female presented with rapidly increasing dementia for the past two months, aphasia, hallucinations, and oculomotor and facial apraxia. Twenty months prior, the patient presented to an outside facility with dementia and gait disturbance and was diagnosed with Parkinson’s dementia. She demonstrated some initial improvement with carbidopa/levodopa, but the effect was only temporary. Eleven months prior to presentation at our institution, she underwent nasal surgery and afterward developed increasing confusion and hallucinations. Nine months prior to presentation, she had a fall and developed epidural and subdural hematomas, which confounded the clinical and imaging findings. The brain MRI demonstrated asymmetric restricted diffusion involving the striatum and frontal/temporal/insular cortex with notable involvement of the cingulate gyrus (Figure ). Using the 2011 UCSF modified grading system, the imaging met criteria for “MRI definitely CJD.” There was no record of an EEG performed. A lumbar puncture was obtained demonstrating positive RT-QuIC, T-tau protein >4000 (positive), and positive 14-3-3 protein. The patient’s do-not-resuscitate (DNR) was signed the same day the lumbar puncture results returned, and the patient was discharged a few days later with hospice services (20 months after initial presentation).
pmc-6384041-5	A 60-year-old male with a history of hemochromatosis, type 2 diabetes mellitus, and hypothyroidism presented to an outside hospital with word finding difficulty and blood glucose level of approximately 400 mg/dL (with HbA1c 13.1%). An MRI performed at the outside hospital was interpreted as only demonstrating age-related white matter changes. The patient experienced declining mental status with unintelligible speech two weeks after presentation and intermittent jerking and weakness of the right upper extremity. With continuing decline, the patient was transferred to our facility three weeks after initial presentation. A new MRI was performed at our facility, which demonstrated asymmetric (left greater than right), diffuse DWI hyperintensity of the bilateral cortex and striatum (Figure ). Using the 2011 UCSF modified grading system, the imaging met criteria for “MRI definitely CJD.” Results for CSF studies returned two weeks later and were negative for RT-QuIC, positive for T-tau, and inconclusive for 14-3-3 protein due to blood in the sample. An EEG showed generalized rhythmic delta activity with delta brush. Neonates normally may demonstrate a delta brush, which abates within the first month of life. Pathologically, the delta brush is a nonspecific sign of metabolic or structural abnormalities and often portends a worse prognosis in adult patients []. At this time the patient had a tracheostomy and would not follow any commands. The patient was transferred to hospice three months after the initial presentation.
pmc-6384043-1	A 19-year-old girl was presented with complaints of non-radiating localised pain in the epigastrium for four months, not associated with vomiting, fever or bowel habit irregularities. Her past medical history was insignificant except for a minor trauma to her upper abdomen three years back when she was evaluated for an incidentally detected retroperitoneal solid cystic mass lesion. Her abdominal examination showed an ill-defined mass in the epigastric region which was firm and non-tender. Ultrasonography of the abdomen showed a solid mass lesion with heterogeneous echo texture in the lesser sac arising from the pancreas. Further imaging evaluation with the contrast-enhanced computed tomography (CECT) abdomen showed an exophytic, well defined and encapsulated solid heterogeneously enhancing mass lesion arising from the body of pancreas pushing the stomach (Figure ). There was also compression of the splenic vein along with partial compression of portal vein (PV) at the confluence and few perisplenic collaterals were noted. A clinical diagnosis of solid pseudo papillary neoplasm was made and we proceeded for laparotomy with the intent of curative resection. The abdomen was opened by a midline laparotomy instead of the rooftop incision for cosmetic benefit. Intraoperatively, we found a highly vascular 10 × 10 cm lobular mass of variegated consistency arising from the proximal body of pancreas in the lesser sac with dense adhesions to the greater omentum and posteriorly to the Toldt’s fascia. The mass was densely adherent to the splenic vein near the confluence. Figure showed an intra-operative photograph of the tumor being mobilized from the confluence showing the superior mesenteric vein (SMV) and the portal vein which were free. The splenic artery was found to be coursing through the mass. The proximal pancreas was normal and distally more than 5 cm of the tail region of pancreas was un-involved. No metastatic deposit or regional nodal disease was evident. Decision was taken to proceed with central pancreatectomy. The lesser sac was opened and the gastroepiploic vessels along the greater curvature of stomach meticulously preserved. A gentle blunt adhesiolysis was done from the posterior wall of stomach. The part of pancreas containing the tumor was carefully dissected from SMV-PV axis and we found that the splenic artery was coursing through it. The tumor was densely adherent with the splenic vein at the confluence and both artery and vein needed ligation for tumor resection. Splenic artery was ligated proximally and distally to the tumor in view of encasement. Further mobilisation of middle segment of pancreas was done distally to facilitate anastomosis. A margin of 1 cm on either side of tumor was ensured and the tumor was resected. Distally normal pancreas more than 5 cm was preserved and the splenic hilar blood vessels were undisturbed. Central pancreatectomy was done and a handsewn, two-layered, end-to-side, duct-to-mucosa type anastomosis was fashioned between the distal pancreas and a retrocolic Roux loop of jejunum. The proximal end of the duct margin was doubly ligated. The maintenance of adequate splenic and distal pancreatic blood supply was achieved by preserving the short gastric and the left gastroepiploic vessels. At the end of the procedure, we were able to demonstrate adequate blood flow into the preserved distal splenic vessels within the distal pancreatic stump. The spleen was burgundy-colored and there was enlargement of spleen, both of which suggested adequate retrograde blood supply. The postoperative period went uneventful. A check CECT angiography was done on third post-operative day which highlighted a fully enhancing spleen and distal pancreas. Figure showed a CECT cross-sectional image in the arterial phase showing the terminal splenic artery stump enhancement in the distal pancreatic stump and an adequate splenic enhancement. There was contrast flow into the terminal splenic artery stump up to the point of ligation via the left gastroepiploic vessels and in turn to the right gastroepiploic vessels suggesting adequate retrograde vascularity. The short gastric artery was enhanced adequately. The patient was discharged safe and well. At follow-up, after a month and three months, she was doing well. The histopathology revealed a well-encapsulated lesion composed of tumor cells arranged in sheets and pseudopapillary pattern with fibrovascular cores (Figure ). Tumor cells were small, round and uniform with moderate to abundant cytoplasm, fine chromatin and inconspicuous nucleoli. Immunohistochemistry was positive for CD56 and progesterone receptors. Hence, a final pathological diagnosis of solid pseudopapillary neoplasm was made. Aggressive features were identified including large tumor size (9 × 5 × 5 cm), focal capsular infiltration and perineural invasion.
pmc-6384044-1	A 48-year-old man with diabetes mellitus who had failed to adhere to his treatment presented to the emergency department with complaints of a right-sided headache and toothache for two weeks, with nausea and vomiting for two days prior to presentation. The patient was managed for septic shock secondary to dental abscesses. Non-contrast brain computed tomography (CT) was performed. The CT scan showed no significant intracranial abnormality other than pansinusitis, without obvious retro-orbital fat streakiness (Figure ). Four days later, tooth number 17 and 18 in the left mandibular region, both of which had abscesses, were extracted. The patient noted progressive painless blurring of the vision in his right eye post-extraction of the abscessed teeth and was referred to the ophthalmology team two days later. At this time, the patient was receiving day five of treatment with intravenous (IV) amoxicillin-clavulanate, (1.2 g three times a day), with the addition of IV metronidazole (400 mg twice a day). The visual acuity (VA) in his right eye was 4/60, with no improvement in the pinhole test. A relative afferent pupillary defect was present, with an associated decrease in the optic nerve function, in addition to ophthalmoplegia and restrictions in the superior and lateral gaze. No proptosis, ptosis or lid swelling was present, and all other anterior segment findings were normal. A fundus examination of the right eye showed only proliferative diabetic retinopathy. The VA in the patient’s left eye was 6/18 and 6/9 in the pinhole test. An examination of the anterior segment was unremarkable. Moderate non-proliferative diabetic retinopathy was detected in the posterior segment. Dental caries were present in the upper molars, with mucopurulent discharge from the right sphenoid sinus region. The clinical diagnosis was OAS, and emergency functional endoscopic sinus surgery and septoplasty were performed by the ear, nose and throat (ENT) team. Intra-operatively, pus (6cc) was drained from the right sphenoid sinus. The pus breached the anterior sphenoid wall, tracked down to the septum polypoidal mucosa over the right maxillary sinus and right anterior and posterior ethmoid sinuses. Empirical treatment with IV ceftriaxone (1 g twice a day) and IV fluconazole (400 mg once a day) was started. Despite the commencement of IV antibiotic and antifungal treatment, the patient’s condition deteriorated, and the VA in this right eye was classified as no perception of light (NPL) and almost total ophthalmoplegia four days post-presentation (Figure ). Treatment with IV methylprednisolone was not started in view of the infective nature of the disease and the possibility of a fungal infection, which could worsen his condition. Methicillin-resistant Staphylococcus aureus was isolated from the pus and from a nasal swab. IV vancomycin (1 g twice a day) and IV metronidazole (400 mg twice a day) were added. An urgent non-contrast CT brain scan was repeated and revealed features suggestive of fungal pansinusitis, with the involvement of the right orbital apex and right orbital contents (Figure ). No suspicious intracranial lesion was seen. The patient underwent emergency nasal debridement for the second time and septotomy. A bony dehiscence was noted over the right posterior ethmoid supralaterally, exposing the orbital apex. On day 13 after the first surgical drainage, tissue culture from the septal wall yielded S. apiospermum. IV amphotericin B (35 mg once a day) was commenced. However, the patient’s renal profile deteriorated following the amphotericin B treatment. Thus, the antifungal regime was changed to oral voriconazole (200 mg twice a day), but the patient failed to respond to the treatment. Forty days after the initial presentation, he developed invasive pansinusitis, with disease progression involving the base of the skull (both orbits) and intracranial extension. At this stage, the VA in the patient’s right eye was classified as NPL in all four quadrants, with almost total ophthalmoplegia. The VA in his left eye was 6/12, with full extraocular movement. The neurosurgical team decided against any surgical intervention. Functional endoscopic sinus surgery was performed for the third time, with nasal toileting. Intra-operatively, minimal crusting was observed over the right nasal cavity. The right sphenoid, pterygoid, maxillary sinuses and the frontal sinuses were clear, with no pus. The mucosa was healthy, with minimal bleeding. The left maxillary sinus was also clear. IV amphotericin B was restarted, but the patient developed gastrointestinal intolerance. The antifungal treatment was again changed to oral voriconazole (200 mg twice a day). Fifty-seven days after the initial presentation, the VA in the patient’s left eye decreased suddenly to 6/30 (reduced Snellen chart), and his colour vision decreased. A plain and contrast-enhanced CT scan of the brain, orbit and the paranasal sinuses showed invasive pansinusitis, with bilateral orbital apex involvement (Figure ). It also showed an increasing intracranial extension involving the right cavernous sinus anteriorly, the roof of the sphenoid sinus, the floor of the anterior cranial fossa and right medial cranial fossa anteriorly, as well as osteomyelitis changes at the base of the skull. In view of the acute progression of the infection, surgical intervention was considered. However, the area of the lesion was too extensive and was beyond ophthalmology coverage. Following a reassessment by the neurosurgical team, a decision was made to continue medical treatment rather than perform a surgical intervention. SIxty-seven days after the initial presentation, the patient’s VA decreased to NPL in both eyes. Although his Glasgow coma scale was full, his general condition worsened, with lethargy, irritability and dizziness, accompanied by nausea and vomiting. The patient decided to discharge himself from the hospital (at own risk discharge) and subsequently failed to attend an appointment in the ophthalmology clinic.
pmc-6384048-1	A 19-year-old male patient with no significant past medical history presented to the emergency room (ER) at the Peruvian Air Force Hospital. He had been experiencing four hours of abdominal pain and emesis. He added that he had been on a strict regimen of dieting and exercise and had lost significant weight in the past months. Symptoms started after heavy meal ingestion and consisted of abdominal oppressive pain and distention accompanied by nauseas and bilious emesis. The family member stated the patient was undergoing a strict carbohydrate restriction, increase in daily exercise and had lost 25 kg in seven months. On physical examination, the patient adopted dorsal decubitus position with knees flexed towards chest. Abdominal examination revealed scaphoid abdomen, diminished high-pitched bowel sounds and tender abdomen in mesogastrium and epigastrium regions. Laboratory workup was within normal limits. The patient stayed overnight in the ER and was managed conservatively with Nil per os (NPO), intravenous crystalloid rehydration, nasogastric tube, ondansetron and omeprazole. Next day reevaluation showed persistence of abdominal pain, nausea and bilious emesis. Computed tomography study revealed gastric dilatation extended to the third portion of the duodenum, suggestive of proximal small bowel obstruction. The patient was admitted for inpatient treatment. After general surgery consultation, he underwent computed tomography angiography (CTA) which found a narrow aortomesenteric angle 18° (Figure ) and a distance between these structures of 7.48 mm (Figure ). Studies confirmed the diagnosis of small bowel obstruction due to SMAS. Initial management included gastric decompression by placing a nasojejunal feeding tube to alleviate symptoms of obstruction and later use for enteral nutritional support. A normocaloric hyperproteic formula was used starting with 600 and progressed to 1500 kcal per day to reverse protein caloric malnutrition state. Psychology and psychiatry departments were consulted concerning major weight loss. The patient was diagnosed with depression and an eating disorder. Sertraline was added to his treatment. The patient was discharged asymptomatic, with hyperproteic diet plus nutritional supplements and selective serotonin reuptake inhibitor. The patient's follow-ups showed weight gain and no symptoms. Psychiatry and psychology teams will follow up the patient after discharge.
pmc-6384050-1	An 18-year-old male patient was referred to our unit for the management and follow-up of epilepsy diagnosed during childhood. The patient had focal seizures evolving to bilateral tonic-clonic seizures treated initially with valproic acid. Seizures were well-controlled until a year before presentation when the seizure pattern recurred. His family history was incomplete due to the absence of the father during upbringing. The patient’s mother was 17 years old when she became pregnant. The medical history was relevant for short stature due to growth hormone (GH) deficiency, with no substitution during childhood due to financial limitations. The general physical examination revealed short stature (133 centimeters) and low weight (45 kilograms) with a body mass index (BMI) of 20.93 (normal BMI: 18.5-24.99). His vital signs were within normal limits. The neurological examination was relevant for complete right eye blindness with atrophy of the right optic nerve and diminished visual acuity in the left eye; a right horizontal nystagmus was found in the neutral position, which worsened with right lateral gaze. Muscle strength was diminished in the left hemibody with ipsilateral hyperreflexia and extensor plantar response. Magnetic resonance imaging (MRI) reported the following findings: - Agenesis of the septum pellucidum, which conditioned a “mono-ventricle” appearance and agenesis of the anterior portion of the falx cerebri - Closed-lip schizencephaly in the right frontal-temporal area, associated with generalized cortical dysplasia of the surrounding parenchyma - Hypoplasia of the corpus callosum - Polymicrogyric appearance and disposition in the left transitional frontal-parietal area - Hypoplasia of the pituitary stalk, the optic chiasm, and both optic nerves (Figure ) Topiramate was started, with excellent seizure control. Endocrine testing revealed low insulin-like growth factor-1 (IGF-1) and growth hormone (GH) levels while the rest of the hypothalamic-pituitary function tests were normal. As part of seizure evaluation, an electroencephalogram (EEG) was performed; relevant findings included asymmetry of right hemisphere electrical activity and epileptiform discharges with a right-frontal focus (Figure ). Due to the presence of the characteristic midline abnormalities along with cortical dysplasia, a diagnosis of septo-optic dysplasia plus was made.
pmc-6385322-1	A 42-year-old male with a past medical history of chronic systolic heart failure (ejection fraction [EF] 25%), status post implantable cardioverter-defibrillator (ICD) 2 years ago, diabetes mellitus, and hypertension, presented to the emergency department complaining of fever for 1 day and intermittent purulent discharge from the ICD site for the past 2 months. He has a history of medication noncompliance and current illicit drug use. Evaluation revealed temperature of 38.6°C, heart rate 112 beats per minute, blood pressure 99/55 mm Hg, respiratory rate 24 breaths per minute, and O2 saturation 94% breathing ambient air. There was erythema and swelling around the ICD pulse generator. Closed sinus was seen with no active discharge, and the area was warm and tender to palpation. Blood cultures were collected, and he was started on vancomycin and meropenem due to his penicillin allergy. His blood pressure dropped further, and he went into septic shock with respiratory failure requiring intubation. Blood culture grew methicillin-sensitive Staphylococcus aureus (MSSA) in 2 sets. Transthoracic echocardiogram (TTE) showed EF 20%, with no evidence of lead or valve vegetations. Antibiotic was de-escalated to cefazolin, and he was extubated successfully in 2 days. The ICD pulse generator and lead were extracted successfully without complication. Culture from the pocket grew MSSA, but blood culture remained negative. He was fitted with a LifeVest and had finished 6 weeks of cefazolin intravenously with no recurrence of infection 5 months after discharge. He was not considered for new device implant unless he proves commitment to quitting drug use.
pmc-6385322-2	An 81-year-old male with history of heart transplant 30 years ago on chronic immunosuppressive therapy and a permanent pacemaker implanted at the time of transplant with 3 revisions most recently 7 years ago. He has been treated for recurrent S epidermidis bacteremia for several years with no clear source. The patient presented this time with 1 week of fever and malaise. The pacemaker site looked noninfected. Blood culture grew methicillin-resistant S epidermidis in 2 sets. Thorough workup including TEE was negative for a source. Since he had high-grade bacteremia (2 sets of positive blood culture) with an organism commonly implicated in device infection, a decision was made to treat as device endocarditis. The pacemaker pulse generator and leads were extracted with the use of laser. There was no evidence of vegetations on the tricuspid valve or leads on intracardiac echocardiogram, which was used to guide the procedure and monitor for complications. Culture of a cloudy fluid from the lumen of the atrial lead showed heavy growth of coagulase negative Staphylococcus, further supporting the diagnosis of device endocarditis. He required temporary transvenous pacing for few days and discharged to a nursing facility to continue vancomycin for a total of 4 to 6 weeks. At 3-month follow-up, he had no recurrence of sepsis; neither did he require device reimplantation.
pmc-6385322-3	A 54-year-old male with a past medical history of nonischemic cardiomyopathy, EF 20% and ICD in situ, gout with extensive tophi, chronic lymphocytic leukemia on ibrutinib, and venous thromboembolism on rivaroxaban. He felt as if the ICD fired. Vitals were normal and ICD site looked normal. There was no evidence of arrhythmia or shock therapy on device interrogation. During hospital stay, he became febrile and hypotensive, blood cultures were collected, and he was started on broad-spectrum antibiotics. Blood cultures grew MSSA in 2 sets. Antibiotics were de-escalated to cefazolin. Transesophageal echocardiogram (TEE) was performed with no evidence of vegetations. He also noted drainage of white cheesy material from an elbow tophus; cultures from these grew MSSA as well. Blood cultures remained negative when repeated 2 days after starting the antibiotic. The infected tophus was determined to be the likely source of bacteremia, and with the clearance of bacteremia and absent vegetation, the ICD was left in place. He was discharged to a skilled nursing facility to complete 2 weeks of intravenous antibiotics. There was no evidence of recurrence of infection at 2-month follow-up.
pmc-6385391-1	A 4-year-old boy, who had no systemic or inherited disease, presented with a 3-week history of intermittent vomiting without diarrhea or abdominal pain. In the past year, he experienced polydipsia and polyuria. Physical examination revealed body weight 17.5 kg (50th percentile), body height 100 cm (15~50th percentile), blood pressure 230/120 mmHg, heart rate 138 /min, and decreased skin turgor. There was no focal neurological deficit, blood pressure discrepancy between upper and lower extremities, palpable mass, nor any appreciation of an abdominal thrill. Laboratory studies revealed serum Na+ 124 mmol/L, K+ 2.4 mmol/L, Cl− 87 mmol/L, Ca2+ 8.5 mg/dL, HCO3− 34.5 mEq/L, creatinine 0.41 mg/dL, albumin 3.4 g/dL, IgG 247 mg/dL, and osmolality 290 mOsm/KgH2O. Urine analysis was significant for creatinine 11.2 mg/dL, Na+ 24 mEq/L, K+ 18 mEq/L, Cl− 24 mEq/L, osmolality 232 mOsm/KgH2O, RBC 168/μL, FENa 6%, and nephrotic-range proteinuria (55 mg/m2/hour). Survey for possible glomerulonephritis demonstrated the absence of anti-streptolysin O, p-ANCA, c-ANCA, ANA, and normal immunoglobulin A, C3, and C4 levels. In addition, work-up for secondary hypertension included: free T4 1.51 (normal range 0.8–2.0 ng/dL), TSH 5.7 (normal range 0.25–5.00 μIU/mL), cortisol 40.18 (normal range 4.3–25 μg/dL), ACTH 9.32 (normal range < 46 pg/mL), renin 1745 (normal range 2–15 ng/L), aldosterone 92.6 (normal range 4–25 ng/dL), and urine vanillylmandelic acid 3.8 (normal range 1.9–9.9 g/day). Renal ultrasonography revealed hyperechoic right kidney (7.6 cm in length) and small left kidney (5.3 cm in length). Due to the presence of hyperreninemic hypertension, natriuretic-hyponatremia, hypokalemia, and nephrotic range proteinuria, HHS was highly suspected. Computed tomography angiography confirmed high-grade renal artery stenosis with hypoplasia of the left kidney (Fig. ). In terms of management for this case, we began with volume repletion by normal saline administration. Subsequently, his blood pressure declined from 210/120 mmHg to 180/90 mmHg. Intravenous calcium channel blocker was used to treat his hypertensive emergency, while oral captopril was prescribed for RAA axis blockage after diagnosis of unilateral renal artery stenosis. The systolic blood pressure gradually declined to 150~160 mmHg on the 3rd day. Potassium supplement was infused for his profound hypokalemia and generalized muscle weakness. Due to the severity of left renal artery stenosis, he was not a candidate for angiographic intervention, and decision was made to proceed with left nephrectomy. Overall, electrolyte abnormalities such as hyponatremia and hypokalemia were corrected within 1 week after admission, and resolution of polyuria, polydipsia, proteinuria, and hypertension were achieved 2 weeks after nephrectomy (Additional file : Table S1).
pmc-6385394-1	A 5-week-old boy was admitted to our department for jaundice and failure to thrive. He had been delivered in another neonatal centre by Cesarean section, from nonconsanguineous healthy parents, at 38 weeks of gestation, with an Apgar score of 9/9. His birth weight was 2600 g (3rd percentile), length 49 cm (27th percentile) and cranial circumference 32.5 cm (5th percentile). Urinary Cytomegalovirus test was negative, as was his family history for known diabetes, hepatic or renal disease; he had a healthy 8-year-old brother. The baby had been discharged from the other centre, in a satisfactory condition, on the 4th day of life. Our physical examination was unremarkable, except for skin and scleral jaundice. The baby also had hypocholic stools. Routine blood tests confirmed cholestatic jaundice (total bilirubin 11.95 mg/dL, conjugated bilirubin 6.69 mg/dL) with increased gamma-glutamyl transpeptidase (GGT 221 U/L), which persisted after ursodeoxycholic acid treatment (20 mg/Kg/day). Fat-soluble vitamins supplementation was started and cow’s milk with highly hydrolyzed proteins enriched with medium chain triglycerides was recommended. Routine screening for cholestatic diseases, including primary investigations for Alagille syndrome, was negative except for a minor pulmonary artery stenosis at echocardiography and a doubt of a thoracic butterfly hemivertebra. Abdominal ultrasound (US) examination revealed a normal liver for size and echogenicity, normal biliary intrahepatic and extrahepatic tree, regular liver vessel flow and hyperechogenic kidneys, with multiple bilateral cortical cysts (maximum size 2 mm). Renal function was impaired (serum creatinine 0.59 mg/dL, estimated glomerular filtration rate 35 ml/min/1.73m2, Chronic Kidney Disease KDIGO stage 3), with metabolic acidosis and tubular proteinuria; he also had polyuria (7 mL/Kg/h) during hospitalization with depressed bregmatic fontanelle. The laboratory tests performed during hospitalization and follow-up are reported in Table . The presence of hyperechogenic kidneys, with multiple bilateral cortical cysts at US examination, associated with a moderate alteration of renal function, were suggestive of ciliopathy. Hepato-biliary scintigraphy showed no passage of bile. A liver biopsy was performed, revealing PILBD with biliary stasis (Fig. ). The association of cholestasis and PILBD, other than the renal involvement, led us to reconsider the diagnosis of AGS and to perform genetic tests for liver cholestatic diseases. The baby continued to have hypocholic stools and persistent cholestasis whilst hospitalized. Although renal function was stable, a central venous access device was necessary for the first few weeks to treat the dehydration caused by polyuria. Moreover, a mild hyperparathyroidism was documented and subcutaneous erythropoietin (EPO) administration was started to treat a progressive anemia. He was discharged from our department at the age of 2 months. At the first monthly follow-up, renal function and proteinuria were stable. Because of the persistence of hyponatremia and metabolic acidosis with hyperkalemia, supplemental oral rehydration with sodium chloride and administration of sodium bicarbonate were continued. EPO treatment was still necessary to maintain normal hemoglobin levels. During the following months, his cholestasis remained stable, although the onset of itching required rifampicin administration. His bilirubin level then decreased significantly, reaching a plateau (total bilirubin 2.5 mg/dL, conjugated 2.2 mg/dL) and the color of his stools normalized. There were no alterations in hepatic synthesis indexes or alpha-fetoprotein levels and no signs of portal hypertension. Renal function had a slight improvement, then stabilized to mild chronic renal failure (Chronic Kidney Disease KDIGO stage 2). US examination revealed an enlarged liver with a slightly inhomogeneous structure, but no focal liver lesions. It also revealed bilateral hyperechogenic kidneys of reduced size, whereas cysts were no longer documented. A reduction of fecal pancreatic elastase, with an increase in fecal fat excretion, was observed, probably due to an initial pancreatic exocrine dysfunction. As no pancreatic hypoplasia was evidenced at US examination, a magnetic resonance cholangiopancreatography (MRCP) has been programmed. Genetic tests for liver cholestatic diseases revealed negative results for AGS (JAG1 and NOTCH2). However, subsequent whole exome sequencing (WES) analysis and interpretation, together with variant prioritization analysis, highlighted the presence of a previously described [–] missense heterozygous mutation in the HNF1β gene, p.Arg276Gln (c.827G > A). The mutation is located in exon 4 of the HNF1β gene within the DNA binding domain, leading to the substitution of glutamine by arginine at codon 276 (R276Q). As this novel mutation was absent in the proband’s parents, we concluded that the patient was a carrier of a de-novo mutation. To the best of our knowledge, this is the first patient reported to be a carrier of the p.Arg276Gln mutation presenting with renal involvement associated with early onset cholestasis. At time of writing the baby is 18 months of age, with persistent cholestasis and pruritus, and a normal neurological development.
pmc-6385396-1	A 73-year-old Japanese man with a 2-month history of dysphasia and heartburn first presented to his local doctor and was later admitted to our hospital. He had difficulties in swallowing and eating; did not have melena, epigastralgia, or hematemesis; and had a history of hypertension and no known allergies. At the time of admission, he was taking at lansoprazole 15 mg/day and olmesartan medoxomil 10 mg/day. He did not drink alcohol but used to smoke 30 cigarettes per day for 45 years. His environmental and employment histories were unremarkable. His family history was remarkable for colon cancer in his father and lung cancer in his brother. On admission, his height was 161 cm, body weight was 56.5 kg, blood pressure was 126/62 mm Hg, pulse was 70 beats per minute, temperature was 36.9 °C, and oxygen saturation was 98% while he was breathing ambient air. His conjunctiva was not icteric but slightly anemic. On chest examination, his heart rhythm was regular with no murmur, and his lungs were clear to auscultation. His abdomen was soft, not distended, and not tender. A soft and movable mass was palpable around the epigastrium. The legs and feet showed no edema. Laboratory tests showed a creatinine level of 0.89 mg/dl, blood urea nitrogen level of 12.6 mg/dl, total bilirubin level of 0.3 mg/dl, aspartate transaminase level of 17 IU/L, and alanine transaminase level of 19 IU/L. The patient’s white blood cell count was 8930 per cubic milliliter, hemoglobin was 9.2 g/dl, and platelet count was 438,000 per cubic milliliter. An esophagogastric fiber (EGF) showed type 3 gastric carcinoma in the antrum. The tumor caused pyloric stenosis and invasion to the duodenum, so the patient was admitted to the hospital (Fig. a–c). Staging laparoscopy was performed to assess the extent of tumor spread, and laparoscopic bypass was performed. Staging laparoscopy revealed peritoneal dissemination, and peritoneal lavage cytology revealed tumor cells in the abdominal cavity. We diagnosed L, type 3, circ, cT4a(SE), cNx, pP1, pCY1, M0, stage IV (the Japanese classification of gastric carcinoma). The patient was initially treated with docetaxel 40 mg/m2 on day 1, cisplatin (CDDP) 60 mg/m2 on day 1, and TS-1 120 mg/day on days 1–14, followed by a 2-week recovery period (DCS regimen). Dexamethasone 9.9 mg and palonosetron 0.75 mg were administered on day 1, and dexamethasone 6.6 mg was administered on days 2 and 3 as premedication. The patient had grade 3 diarrhea (according to Common Terminology Criteria for Adverse Events criteria) after one course (Fig. a, b). Then TS-1 was reduced (100 mg). After two courses of the DCS regimen, EGF and computed tomography (CT) showed that the tumor had shrunk (Fig. c–e), and then staging laparoscopy was performed to evaluate a response. Peritoneal dissemination disappeared, and peritoneal lavage cytology revealed no tumor cells in the abdominal cavity. Then salvage operation, laparoscopic distal gastrectomy with D1+ dissection, was performed. Pathological findings were ypT2(MP), ypN2(3/15), ypP0, ypCY0, M0, ystage II (Fig. ). TS-1100 mg/day on days 1–14, every 3 weeks was started as adjuvant chemotherapy. After 15 months, CT revealed multiple peritoneal nodules (Fig. a). They were highly suspected as a recurrence. Paclitaxel 80 mg/m2 on days 1, 8, and 15 was started as a second regimen. Dexamethasone 6.6 mg, famotidine 20 mg, and granisetron 3 mg were administered on days 1, 8, and 15 as premedication. This regimen achieved partial response (Fig. b), but its efficacy did not last. After 3 months, CT revealed progressive disease (Fig. c). The original gastric carcinoma was HER2-positive (Fig. ). The patient’s Eastern Cooperative Oncology Group performance status was 2; his body weight was 50.7 kg; and he complained of appetite loss. We concluded that the patient could not tolerate doublet therapy. Therefore, TS-1100 mg on days 1–14 with Herceptin 6 mg/kg (Roche/Genentech, South San Francisco, CA, USA) on day 1 every 3 weeks was introduced. This regimen was substantially effective and achieved CR after 9 months based on CT findings (Fig. d, e). The patient had no adverse effects while receiving this regimen (Fig. a, b). Since then, the patient has been treated with only Herceptin 6 mg/kg every 3 weeks without any side effects, and no radiological findings of recurrence had yet occurred for 6 years, 7 months after surgery (Fig. f).
pmc-6385398-1	Here, we report on a 53-year old patient with stage IV melanoma who was admitted to the hospital after he presented with generalized paresthesia, stiffness in both hands, a feeling of obstruction in his throat and mild dizziness. He had metastases in the liver, spleen, lung and bones but not in the brain (Fig. a). Treatment of his melanoma with nivolumab 1 mg/kg and ipilimumab 3 mg/kg was started 4 weeks earlier and two doses had been given before the time point of presentation. He reported a significant worsening of symptoms over the past few days. His medical history included arterial hypertension treated with valsartan and bisoprolol and intermittent stomach complaints treated with pantoprazole. He had no known auto-immune disorders before the treatment with nivolumab and ipilimumab was started. Serologies for hepatitis B and C virus were negative before the start and serum levels of TSH and free T4 were within the normal limits. At presentation, his vital signs showed no abnormalities. Physical examination was unremarkable with negative Chovestek’s and Trousseau’s signs. ECG showed a prolonged corrected QT interval (493 ms). Laboratory testing revealed hypocalcemia (calcium 1,35 mmol/l [normal range 2.10–2.65], albumin 38 g/l [normal range 35–52], ionized calcium 0,7 mmol/l [normal range 1,15-1,3]), marginal hypomagnesemia (0,69 mmol/l [normal range 0,70-1,00]) and hyperphosphatemia (1,75 mmol/l [normal range 0,8-1,5]. Intact parathyroid hormone (iPTH) level was inadequately low (7,2 pg/ml [normal range 15–65]), 25-hydroxy vitamin D3 level was just above normal range (121 nmol/l [normal range 13.2–118]), venous blood gas showed normal pH of 7.418. There was no clinical sign of other auto-immune endocrinopathies, thyroid hormone and cortisol levels were normal. The patient was diagnosed with acute symptomatic hypocalcemia most likely due to immune-mediated hypoparathyroidism and hospitalized for further treatment. He was given a total of 4 g calcium gluconate in divided doses and 3 g of magnesium sulfate (corresponding 12,15 mmol) intravenously. Oral calcitriol and calcium carbonate was started in parallel. Intact parathyroid hormone remained low even after normalization of magnesium. Symptoms subsided after elevation of calcium levels and the patient was discharged on oral treatment. However, two weeks later, he was readmitted with symptoms of hypocalcemia which was triggered by acute vomiting and severe diarrhea (7–8 stools per day, grade 3). No stool pathogens were identified. Colon biopsies revealed regenerative changes of crypt epithelia and focal surface epithelial defects suggestive of an immune-mediated colitis under PD-1 and CTLA-4 blockade. Thus, the patient was treated with prednisone at 2 mg/kg intravenously and upon persistence of symptoms switched to treatment with infliximab (5 mg/kg), which led to a rapid reduction of stool frequency and eventually resolution of the diarrhea. The steroid therapy was tapered slowly over the course of 4 weeks. The infliximab treatment was repeated once after 2 weeks. No further episode of diarrhea occurred. We interpreted the colitis most likely as a consequence of CTLA-4 blockade and therefore decided to continue the PD-1 blocking antibody nivolumab alone. The hypocalcemia was corrected by substitution therapy. 18F-FDG PET/CT at 5 months after initiation of checkpoint inhibitor therapy showed a complete metabolic remission and an almost complete regression of pulmonary, lymphogenic, splenic and hepatic lesions (Fig. b). No enlargement or hypermetabolism was detectable in the typical location of the parathyroid glands. Interestingly, the PTH was increasing during intensified immune suppression with infliximab, but the levels were sinking again during tapering of steroids (Fig. ). The patient had to be constantly substituted with calcium and in addition, was treated with calcitriol. In order to investigate the reason for the hypoparathyroidism, we analyzed antibodies against the calcium sensing receptor (CaSR). We found detectable levels of auto-antibodies against CaSR in this patient. However, when we analyzed control patients that had also undergone immunotherapy with nivolumab and ipilimumab for melanoma, similar levels of auto-antibodies against CaSR were found, suggesting that the detected antibody concentrations were probably not pathogenic and the test for such low concentrations is most likely unspecific. During the course of the treatment, the patient developed 8 months after start of the immunotherapy an inflammatory oligoarthritis with affection of the right knee and the right ankle. The oligoarthritis was well manageable with local steroid injections. Since a complete response was achieved, we decided at this point to stop the PD-1 blockade. After stopping nivolumab, the calcium substitution could be reduced.
pmc-6385406-1	A 20-year-old Japanese man presented with a 2-month history of fever, night sweats, and mild weight loss. He had no rash or palpable peripheral lymphadenopathy. Laboratory tests revealed anemia (hemoglobin, 9.5 g/dL), leukopenia (white blood cell, 2.4 × 109/L), and elevated lactate dehydrogenase (LDH, 1175 U/L; normal range 120–250 U/L). The EBV-DNA level was extremely high in the whole blood (4.0 × 106 copies/mL). Abnormal cells were not detected in the peripheral blood (PB). Other laboratory data are shown in Table . Chest radiography showed bilateral pulmonary lesions predominantly in the upper lung. Computed tomography (CT) showed multiple nodules diffusely mixed with consolidation and ground-glass opacity pattern in both lungs (Fig. ). Enlargement of the mediastinal and hilar lymph nodes and hepatosplenomegaly were also observed. Positron emission tomography (PET)/CT showed abnormal uptake of 18-fluorodeoxyglucose (FDG) in multiple lung lesions, as well as the mediastinal and hilar lymph nodes, bilateral humeral bones, lumbar spine, liver, and spleen. The maximum standardized uptake value (SUVmax) of lung nodules (median, 4.7; range, 3.2–9.6) was lower than that of hilar lymph nodes (median, 16.7; range, 7.5–18.3) (Fig. ). Video-assisted thoracoscopic surgical lung biopsy (VATS) was performed the next day. Visual inspection revealed dark purple patchy lesions on the whole lung surface, and specimens were obtained from the left S6 and S1 + 2. Pathological examination showed large-sized atypical cell infiltration localized mainly in the lumina and perivascular areas of the distended vessels beneath the pleura and in the pulmonary parenchyma (Fig. ). These abnormal cells had irregularly contoured nuclei, prominent nucleoli, and narrow cytoplasm. The tumor cells were positive for cytoplasmic CD3ε, CD56, and perforin, and negative for cytokeratin, CD20, and CD30 by immunohistochemistry. EBV infection was detected by in situ hybridization analysis for EBV-encoded RNA. The Ki-67 proliferation index showed 70–80% nuclear staining. T-cell receptor γ chain rearrangement was not proven, which was consistent with an NK-cell origin. Based on these findings, he was diagnosed with ENKL (Stage IV). The bone marrow was normocellular with an increase in activated histiocytes containing engulfed red blood cells, nuclear debris, and platelets, but no neoplastic cell infiltration was observed. This finding was compatible with hemophagocytic lymphohistiocytosis (HLH). One week after admission, he received combination SMILE regimen chemotherapy (dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide). After two cycles of SMILE, complete remission (CR) was confirmed by FDG-PET/CT, and EBV-DNA became undetectable in the PB. Subsequently, he received a single unit CBT after myeloablative conditioning of cyclophosphamide (120 mg/kg) plus 12 Gy total-body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and mycophenolate mofetil. On day 16, he achieved successful neutrophil engraftment. On day 21, he developed biopsy-proven gastro-intestinal acute GVHD (grade II), which gradually improved with prednisolone at doses of 0.5 mg/kg daily. On day 88, he was discharged in complete remission with no other major complication. Four months later, he developed mild cutaneous chronic GVHD limited to the head and neck, which could be managed with topical steroids. He has been alive with continuous CR for 1 year after diagnosis.
pmc-6385410-1	A 64-year-old man was hospitalized for a few-months history of dull pain in the right groin. Physical examination revealed a palpable mass in the right flank with a mild right flank tenderness. His previous history was uneventful. The results of laboratory examination were unremarkable. Screening ultrasound examination revealed a hypoechoic tumor with inhomogeneous interior echoes, 23 × 13 × 7 cm in size. Computerized tomography (CT) confirmed the presence of a solid tumor of the right kidney about 20 cm in diameter (Fig. a, arrow). Renal arteriography demonstrated a hypovascular tumor and compressed deformity of pelvis of the right kidney (Fig. b, arrow). The left kidney was normal. Suspecting a renal carcinoma the patient underwent a right radical nephrectomy in February 2018. He had an uneventful post-operative recovery, and is currently well without any sign of recurrence. Grossly, the tumor was solitary and sharply defined, measuring 23 × 13 × 7 cm (Fig. a). The cut surface was solid, elastic hard, and white yellowish without hemorrhage or necrosis (Fig. b). The pyelocaliceal system and the renal vessels were free of tumor involvement. Microscopic examination of the tumor disclosed intersecting fascicles of fibroblastic cells forming a loose crisscross or “storiform” pattern (Fig. a). And we observed that there was a clear boundary between the tumor and the kidney tissue under the microscope, which kept in line with the CT representation (Fig. b). The tumor was basically histiocytic, presenting a great deal of collagenic fibers, upon the presence of foam cells. The multinucleated giant cells and undifferentiated mesenchymal cells were very low. In addition, the cells were well differentiated, and the nuclei were not deep stained with very low heteromorphism. Immunohistochemical studies showed that the tumor cells were strongly and positive for CD34, vimentin and CD99, the proliferation index of Ki-67 was 1%, but were negative for the smooth muscle actin (SMA), the desmin, SOX10, Bcl-2, CK7, the melanogenesis marker (HMB45), MelanA and the S-100 protein.
pmc-6385464-1	A.M., a 12-month-old male infant, Caucasian, Italian, in good general health, with no history of recent fever or any other symptoms. The patient was evaluated for erythematous scalp lesions and annular patches combined with hair loss (Fig. ). The infant had not been in contact with animals; her mother and other family members were asymptomatic. No other systemic symptoms were elicited. He was suspected to have a dermatophytosis. The Wood’s light examination revealed a brilliant green fluorescence on the scalp lesions. Mycological analysis of all suspected dermatophyte lesions was performed. Hair and scale samples were collected and examined under a light microscope with 20% v/v KOH + 40% v/v DMSO solution in distilled water. A fungal culture was performed into Mycobiotic agar (Merck, KGAA, Germany) to identify dermatophytes. Plates were incubated at 25 °C and examined every 2–3 days for at last 15 days. Mold identification was based on macroscopic and microscopic assessment of colonies []. Macroscopic examination revealed some white fluffy spreading colonies (Fig. ), and a characteristic deep yellow-orange pigment on the reverse. Spindle shaped multicellular macroconidia with thick cell walls were detected on microscopic examination (Fig. ). Clinical features and culture results reveled TC caused by Microsporum canis. Therapy was started with oral griseofulvin (20 mg/kg/day) with a 2 daily tioconazole cream application. The lesions were also treated with iodized alcohol. At 15-day intervals, the child was subjected to objective examination, including culture tests. The patient was treated for two months in total with both medications and iodized alcohol. After this period of treatment, the first negativization of the culture for M. canis was observed. However, 15 days later at the end of treatment, in the area of the lesions, where hair regrowth was observed, the infant patient presented with a single vesicle with growth of M.canis on culture. Oral treatment with griseofulvin (20 mg/kg/day) was administered for one month. After this period, all scalp lesions were completely healed and cultures resulted negative for dermatophytes. After 3 months of follow-up, no recurrence was observed (Additional file ).
pmc-6385610-1	A 73-year-old man was admitted in Urology ward on 30th September 2017 with a chief complaint of nocturia, frequency, dribbling, and urinary retention since last month. Ultrasound examination revealed left renal mass. In past history diabetes mellitus, hypertension, and ischemic heart disease was noted. He stopped cigarette smoking 20 years ago. His drug history was Enalapril, ASA, Metformin, and Metoral. The lab data including complete blood count, Blood Urea Nitrogen (BUN), creatinine, Na, K, Arterial Blood Gas (ABG), Prostatic Specific Antigen (PSA), and free PSA were within normal limits except for mild anemia (Hemoglobin: 10.6 gr/dl). Blood sugar (BS) was 159 mg/dl. Urine analysis showed 10-15 white blood cells (WBC) in high power field with a negative urine culture. In digital rectal examination prostate was nodular (2-3+) and symmetric. Ultrasound examination on 7th October 2017 demonstrated mild bilateral hydroureteronephrosis with the over distended urinary bladder. Prostatic volume was 25 cc with the retained urine of 950 cc. A well-defined hypoechoic exophytic mass without calcification measuring 60 × 38 mm in left renal pole with vascular areas was noted. Computer tomography scanning on 10th October 2017 revealed 44 × 38 mm hypo attenuated mass in the lower pole of the left kidney with arterial and portal enhancement and delay washout in favor of infiltrative process such as RCC close to left psoas muscle. Mild bilateral hydronephrosis due to enlarged prostate was seen. No lymphade- nopathy in pelvis and abdomen was seen. He referred to surgery department of the hospital for nephrectomy. The specimen was referred to the pathology department. The frozen section microscopic evaluation revealed oncocytic feature in favor of oncocytoma. In permanent diagnosis, a portion of renal tissue measuring 6.5 × 5.5 × 3.5 cm with perirenal fatty tissue measuring 3 × 2 × 1 cm was evaluated. In cut section, creamy brown solid mass measuring up to 5.5 cm at 1.5 cm distance from renal resected margin was noted. The pathologist reported chromophobe RCC () with vascular and renal capsule invasion but with no necrosis or margin involvement. The IHC was done and tumor cells were positive for cytokeratin (CK) 7, CK8, CK20 (weakly +), the Epithelial Membrane Antigen (EMA), Cluster of Differentiation (CD) 10, E-Cadherin and High Molecular Weight Keratin (HMWK, focally positive). Inhibin and vimentin markers were negative in tumor cells (–). The findings were in favor of chromophobe RCC. We followed- up the patient for 5 months after surgery. No recurrence or metastasis was diagnosed.
pmc-6385611-1	Girl M. 7 years old with a diagnosis of osteosarcoma of the right femur, T2N0M0, stage IIB, condition after combined treatment, clinical group II. According to vital indications, anticancer treatment was carried out. PCT using OS-2006 protocol was started on December 6, 17. The second course was held from 15.01 to 22.01.18. During the first two courses of PCT, even against the background of the ongoing medical decontamination, OM of the 1st degree developed. During the 3rd course of chemotherapy, including high doses of methotrexate, it was decided to conduct LLLT and analyze the dynamics of phagocytic activity after three 20-minute sessions of low level laser therapy. The 3rd course was conducted from 02.02.2018 to 23.02.2018 using 0S-2006 protocol: Methotrexate 12 g/m2 on the 1st, 8th days, IV infusor in 4 hours, single dose = 8 g, daily dose = 8 g; Cisplatin 50 mg/m2 on the 15th, 16th days, IV infusor in 24 hours, single dose = 35 mg, daily dose = 70 mg; Doxorubicin 45 mg/m2 on the 17th, 18th days, IV infusor in 24 hours, single dose = 31.5 mg, daily dose = 63 mg. The girl underwent the treatment satisfactorily. Oral mucositis did not develop. It is noted that even 5 days after the termination of PCT, the child has high phagocytic activity. It increased more than 3 times compared with phagocytic activity before LLLT. High phagocytic activity was also noted 4 weeks after LLLT (). We performed non-invasive laser blood illumination to children 1-3 days before the start of chemotherapy. Laser blood illumination was carried out by applying the emitter to the skin above large vessels. These can be zones of the carotid arteries and cubital, subclavian or popliteal veins.
pmc-6385615-1	A 45-years-old male engineer with no history of trauma, presented to us with progressive upper back pain for two months that eventually became severe and disabling. The pain was non mechanical and was present even at rest and night. He denied any constitutional symptoms. He had no significant medical history except that he was a smoker for over 20 years. On neurological examination, patient indicated altered sensation from T8 dermatome and below; however, upper and lower limb motor power was normal. He had an unsteady gait and exaggerated deep tendon reflexes in both lower limbs. Initial X-rays of the thoracic spine were unremarkable, but MRI demonstrated abnormal marrow replacement and enhancement of the entire T6 vertebra including its posterior elements and right 6th posterior rib. MRI axial cuts at T6 level revealed right postero-lateral epidural extension of the lesion causing severe spinal canal, right lateral recess and right exit foraminal stenosis (, ). In addition, an irregular right lung nodule was noted. CT evaluation confirmed the vertebral involvement () and the presence of a lobulated right lung nodule with emphysematous changes in bilateral upper lobes. Further radiological assessment revealed no other lesion elsewhere. During the course of the work up, he developed bilateral lower limb weakness and was unable to stand. A diagnosis of thoracic myelopathy due to cord compression was made and immediate surgical management in the form of T6 decompression laminectomy along with T3-T8 posterior instrumentation was performed (). Surgery was uneventful; patient had good recovery and was ambulating independently. Tissue biopsy from T6 right pedicle revealed presence of metastatic tumour cells with moderate amount of eosinophilic cytoplasm in the marrow spaces suggestive of a metastatic carcinoma with neuro-endocrine features (). Tumour cells were positive for cytokeratin AE1/3, carcinoembrionic antigen (CEA), chromogranin and synaptophysin. Proliferation marker Ki67 was found to be 40%. Early post-operative MRI showed adequate decompression of the spinal canal at T6 level and the patient had interval resolution of symptoms; but there was abnormal fluid collection from the surgical site extending up to the subcutaneous layer, likely to be seroma, which was conservatively managed. Chemotherapy with Carboplatin and Etoposide was initiated after satisfactory wound healing three weeks after surgery. One month after the index surgery, patient developed significant motor deficit in the lower limbs (Right L2-L5 = 2/5; Right S1 = 4/5; Left L2-S1 = 4/5) and had bowel and bladder incontinence. An urgent MRI was done which revealed recurrence of the lesion causing near total obliteration of the spinal canal (). A second surgery at this stage was considered high risk and the decision was made to initiate concurrent site specific T4-T7 radiotherapy (30 Gy in 10 fractions) along with chemotherapy. Interestingly at the end of radiotherapy and four courses of chemotherapy (4 months post-op), there was significant clinical improvement of neurology and complete resolution of the soft tissue enhancement surrounding the spinal cord was evident in the MRI (). With appropriate physiotherapy and rehabilitation, patient gradually regained full power in both lower limbs by 6 months. He continues to be under oncology follow up and is ambulant with support.
pmc-6385819-1	A 45-year-old man with a previous diagnosis of BD for two years was admitted to the emergency department due to acute chest pain. The patient had no history of diabetes mellitus, hyperlipidemia or hypertension, while he had 25 pack-year history of smoking. There was total occlusion of the right superficial femoral artery on computed tomography scan (). His electrocardiogram revealed a significant ST segment elevation on anterior derivations. Cardiac troponin (7.263 ng/mL, 0-0.1 ng/mL) and creatine kinase-MB (63 U/L, 0-25 U/L) levels were elevated. After the patient was transferred to the coronary care unit with the diagnosis of acute anterior myocardial infarction, an emergent coronary angiography was performed. Coronary angiography demonstrated coronary dissection in the LAD (). Once diagnosed, the patient was taken up for emergency surgery and underwent CABG using the LIMA to LAD and the saphenous vein for RCA surgery. The intimal dissection originated from the LAD was observed intraoperatively (). Five days after surgery, the patient was discharged after an uneventful hospital stay.
pmc-6385823-1	This case report was prepared following the CARE Guidelines[ and the patient provided informed consent for its publication. We present a case of a 23-year-old man who was diagnosed with Kawasaki disease at the age of 13 months when he suffered an acute coronary syndrome (ACS). Coronary artery aneurysms in RCA and LMA were observed, as well as partial thrombosis in both. Accordingly, he was treated with fibrinolysis and anticoagulant therapy. Complete regression of the RCA aneurism was observed six years after the diagnosis of Kawasaki disease, however the LMA aneurysm persisted with involvement of the anterior descending artery ostium. One year before the current episode, the patient suffered from ACS due to a severe calcified lesion of the LMA aneurysm (). He underwent an emergency percutaneous coronary angioplasty, and a polyurethane-covered stent (PK Papyrus, Biotronik(r), Berlin, Germany) was inserted. The patient remained asymptomatic for one year. In the current episode, he was readmitted to the emergency department in cardiogenic shock in which noradrenalin employment was necessary to achieve hemodynamic stabilization. He suffered from ACS caused by a complete occlusion of the stent despite anticoagulation and dual antiplatelet therapy. It was possible to percutaneously reopen the occluded LMA and adequately restore coronary flow. However, there was evident severe stent malposition in the distal part of the LMA. Due to this concerning finding, the patient was accepted for emergency cardiac surgery. He underwent off-pump CABG 24 hours after the episode, in which both internal mammary arteries (IMA) were dissected. The right IMA was grafted to the left medial anterior descending artery, and the left IMA was grafted to the first marginal artery. A transit-time flow meter was employed to assess graft patency (Medistim(r), Oslo, Norway). Although flow measures and pulsatility index (PI) were optimal (60 ml/min in the right IMA graft and 50 ml/min in the left IMA graph, with a PI of 2.4 and 75% insufficiency), a high degree of competitive flow was observed through the recently reopened LMA. A transitory tourniquet was applied to the LMA () and there was great improvement in the flow through the grafts with complete disappearance of any competitive flow (150 ml/min and 80 ml/min in right and left IMA, respectively, and insufficiency decreased to 0%). Therefore, the LMA was ligated at the inflow of the aneurysm. The patient was discharged after 24 hours in intensive care after surgery and a total stay of six days. The patient has remained asymptomatic since the procedure with a post-operative follow-up at 16 months to date.
pmc-6385824-1	Case 1 - A 14-months-old female patient was submitted to surgical excision of a right atrial aneurysm on March 30, 1999[. The diagnosis of congenital heart disease had been suspected by ultrasonography during fetal life. She was admitted to the emergency room of our institution presenting a paroxysmal supraventricular tachycardia which subsided with digoxin. Subsequently, she presented several episodes of arrhythmia. Physical examination was normal. Chest X-rays showed marked cardiomegaly. The electrocardiogram was normal. Echocardiogram demonstrated a massively dilated right atrium without any intracardiac abnormalities. Cineangiography confirmed the presence of a large aneurysm on the right atrium. Surgery was performed through a median sternotomy and normothermic cardiopulmonary bypass. The entire right atrium body was aneurismatic, but the atrial appendage was normal. The aneurysm was resected as much as necessary to simulate a normal-sized right atrium. The resected tissue measured 11 x 6 cm. The remaining right atrium was closed with a continuous 6-0 Prolene suture. The postoperative course was uneventful. She is now a 19-years-old health woman who had a normal pregnancy a year ago bearing a normal child. No episode of arrhythmia has occurred. Chest X-rays (), electrocardiogram, and echocardiogram are normal.
pmc-6385824-2	Case 2 - A 14-years-old male patient who had been diagnosed intra-uterus with congenital aneurysm of the right atrium was referred to our institution for surgical treatment. He had symptoms of frequent palpitations. Physical examination was normal, except for a systolic murmur grade 3/6 heard at the tricuspid area. The electrocardiogram was normal. The chest X-ray showed enlargement of the cardiac area (). Echocardiogram revealed aneurysmal dilatation of the right atrium and moderate tricuspid regurgitation. On November 24th, 2016, the patient underwent surgical correction (). Under conventional cardiopulmonary bypass, the right atrial aneurysm was resected. The tricuspid valve was normal, but the annulus was dilated and a ring annuloplasty was performed. The postoperative course was uneventful. Chest X-ray () and echocardiogram are normal.
pmc-6385834-1	A 22-year old male patient was referred to our clinic with exertional angina. His history revealed pulmonary hydatidosis treated through cystectomy and capitonnage followed by 12-week oral albendazole treatment (400 mg/twice a day) five years ago. Chest X-ray and thoracic computed tomography (CT) exposed only few scattered calcifications within pulmonary parenchyma (). Cineangiography of the patient with ST segment depression in exercise test revealed that the left diagonal artery (LAD) and 1st diagonal arteries were proximally occluded (). In transthoracic echocardiography, a cystic mass of 2x2 cm with well-defined borders was detected on the left ventricular anterior wall (). The patient was taken into operation for coronary artery bypass grafting. Operation was carried out under cardiopulmonary bypass instituted after median sternotomy. The mass, with size of 2x2 cm and regular borders, was found to be located between the left main and LAD coronary arteries (). Since calcified, the cyst was isolated en bloc with the coronary artery segments it had infiltrated (). Free ends of the coronary arteries opening into the cavity left behind after cyst excision were ligated. Capitonnage was performed after irrigation with hypertonic saline solution. Following that, LAD artery and 1st diagonal artery were bypassed. Macroscopically, it was detected that the cyst contains clear colorless fluid (eau de rock). Microbiological and pathological analysis of both the cyst and its ingredients revealed findings consistent with the hydatid cyst. Echinococcal IgG-ELISA test was found to be positive (sensitivity: 94%, specificity: 99%)[. The patient received oral albendazole treatment (10 mg/kg/day; 2x400 mg/day) postoperatively for 12 weeks. During 1-year follow-up, diagnostic tests were negative and no recurrence was observed.
pmc-6385839-1	A 35-year-old female presented with dyspnea on exertion, fatigue and incidents of tachycardia over the past 8 months. She also complained about intermittent, irritating cough sometimes accompanied with blood-streaked sputum. The patient reported being previously on oral contraceptives, for polycystic ovary disease, for which she was finally operated. Because of increasing shortness of breath, she underwent pulmonary workup, where the lung functional tests, including spirometry and carbon monoxide diffusing capacity, were normal. Chest X-ray showed a right lower lobe opacity (). Transthoracic echocardiography revealed a 42 mm left atrial dilatation, accompanied with moderate tricuspid valve regurgitation, moderate pulmonary hypertension and a measured pulmonary artery systolic pressure of 42 mmHg. A chest computed tomography (CT) scan () revealed a solid mass, measuring 7 mm in diameter, in the lower part of the posterior mediastinum, extending 6.3 cm downwards from the level of the carina. The mass was impinging upon the posterior surface of the left atrium, the pulmonary vein orifices and was abutting the right hilum. Calcifications were evident within the lesion. Areas of ground glass opacities were noted in the right middle and lower pulmonary lobes, with thickening of the interlobular septa especially at the periphery of the lung parenchyma, indicative of pulmonary vein inflow obstruction. Subsequently a chest magnetic resonance imaging (MRI; ), confirmed the presence of the space occupying lesion, extending to the subcarinal region. The mass was compressing the right main pulmonary artery, the peripheral part of which did not exceed 7 mm in diameter; it was also in close relation to the azygos vein, the esophagus, the central part of the right mainstem bronchus and the right wall of the descending thoracic aorta. Furthermore, it compressed the posterior aspect of the left atrium, with obliteration of the pulmonary veins. Further workup with fiberoptic bronchoscopy revealed hemorrhagic mucosa with evidence of external compression and stenosis of the right lower lobe bronchus. No endobronchial mass was found and the aspirated lavage was negative for malignancy. A lung perfusion scan with 5 mCi of 99mTc-HAM (human albumin microspheres) followed, demonstrating minimal uptake (5%) of the radioactive substance from the right lung, indicative of severe hypoperfusion. Differential diagnosis included teratoma, lymphoma, sarcoidosis, primary lung cancer, metastatic carcinoma, mediastinal sarcoma or a mediastinal desmoid tumor. Thoracotomy was decided in order to obtain definite diagnosis and also because of the lesion location. Mediastinoscopy was technically impossible, therefore, an exploratory right lateral thoracotomy was performed. Intraoperative findings were in accordance to the preoperative MRI and CT scans. Surprisingly, tortuous, engorged vessels demonstrating a rich collateral between the diaphragm and the azygos, as well as between parietal and visceral pleura were noted. The latter indicated a slow growing mass, which was compensated by the patient. The lesion was hard on palpation, due to the high degree of fibrosis, with areas of calcification. It was tightly adhering to the esophagus, the left atrium, the pulmonary vessels and the right bronchi. Intraoperatively, multiple frozen section biopsies were obtained, as close as possible to the center of the mass. The procedure was vigorous, due to the hard texture of the lesion; the quick-frozen sections were returned negative for malignancy. Mobilization of the esophagus to prevent dysphagia was performed. Complete removal of the lesion was impossible due to its firm adherence to the surrounding vital structures. The patient had a relatively uncomplicated postoperative course, apart from a transient episode of partial right lower lobe collapse, revealed in the chest X-ray and a pneumonitis episode, which responded well to treatment with antibiotics; she was finally discharged on the sixth postoperative day. The pathologic examination revealed dense bands of collagen separated by a chronic inflammatory cell infiltrate of lymphocytes and plasma cells (). Moreover, areas of calcification were also observed. The process extended into the pulmonary parenchyma at the level of the hilum. Stains for acid-fast bacilli and fungi were negative. After an episode of hemoptysis, she was administered steroid treatment (methylprednisolone), based on case study reports; treatment also comprised azathioprine, calcium, vitamin D3, isoniazide and vitamin B6 (due to positive Mantoux test). The patient received an initial dose of 20 mg/d methylprednisolone, which was tapered over the next few weeks to a maintenance dose of 5 mg/d. At the beginning of the treatment, the patient demonstrated elevated inflammatory markers [erythrocyte sedimentation rate (ESR), C-reactive protein CRP)], which were significantly decreased a month later. She also experienced several side effects of steroid treatment, including central obesity, facial hair increase, acne and myopathy. During follow-up, an MRI scan performed two years postoperatively demonstrated 15% decrease in the dimensions of the lesion. A new MRI scan was repeated nine months after the previous one, which showed that the dimension of the lesion remained unchanged (). A new pulmonary workup showed significant improvement in lung functional tests, compared to those two years ago. Clinically, the patient reported moderate improvement of her dyspnea. Additionally, postoperative echocardiography showed a measured pulmonary artery systolic pressure of 15 mmHg. No definite etiological factor was detected, while the patient was on follow-up. Unfortunately, the patient was lost to follow-up 4 years postoperatively.
pmc-6386331-1	A 78-year-old woman presented to the emergency department complaining of paresthesias in her upper limbs and inability to open her hands over the last four hours. The patient experienced weight loss of about 14 kg over the previous 2 months, loss of appetite, and two to three liquid stools per day over the last 3 days. Her medical history revealed a long history of hypertension, osteoporosis. Family history was noncontributory. Her current medications included bisoprolol 2.5 mg daily, calcium/vitamin D3 supplementation, and denosumab 60 mg every 6 months. Initial evaluation in the emergency department revealed marked hypocalcemia with a total calcium 6.0 mg/dL (normal 8.2 to 10.50 mg/dL) and ionic calcium 0.97 mmol/L (normal 1.15 to 1.35 mmol/L), hypomagnesemia (0.56 mg/dL), and normal phosphorus, renal function, white blood count, and hemoglobin. The chest x-ray and the electrocardiogram were normal. She was transferred to the Department of Internal Medicine. On physical exam, the patient looked ill. Blood pressure, heart rate, and oxygen saturation were normal. The cardiorespiratory system examination was normal, as well as the abdominal exam. Neurological exam was normal but she complained of paresthesias. The patient’s laboratory testing revealed no other electrolyte disorders, normal liver function, and normal blood gases. Her folic acid, vitamin D, and serum iron levels were low: 2.7 ug/L (normal: 5 to 15 µg/l), 14 ng/mL (normal: 30 to 50 ng/mL) and 18 ug/mL (normal: 25 to 150 ng/mL), respectively. A normochromic normocytic anemia was found. Albumin and total proteins were also low. Parathormone (PTH) was 452 pg/mL (normal: 0.00 to 68.2 pg/mL). Her thyroid function, lipid panel, and vitamin B12 levels were normal, and sedimentation rate was within the normal range. Autoimmune panel revealed positivity for anti-gliadin IgG antibodies and negativity for anti-transglutaminase and anti-endomysium antibodies. Anti-Saccharomyces cerevisiae antibodies (ASCA) antibodies were negative. The genetic studies revealed positivity for DR3DQ2 and DR4DQ8 haplotypes. Fecal chymotrypsin, calprotectin, and antitrypsin had increased. The patient underwent an upper endoscopy revealing the presence of villous atrophy in the proximal and middle small intestine without ulcers, findings that were consistent with celiac disease. The first abdominal computed tomography (CT) was read as negative. The patient was started on a gluten-free diet and intravenous calcium and magnesium supplementation with good clinical response. One week after admission the patient developed upper right quadrant pain and fever consistent with acute cholecystitis, confirmed by ultrasound, and she was started on intravenous antibiotics. Five days later, she developed edema in the left lower limb and a positive D-dimer. Venous doppler ultrasound and computed tomography of the chest confirmed the presence of deep venous thrombosis and pulmonary thromboembolism. Anticoagulation with low molecular weight heparin was initiated. There was no evidence of right ventricular dysfunction on the echocardiogram. On day 27 of admission the patient complained of acute abdominal pain. The abdominal computed tomography was consistent with intestinal perforation of uncertain location. The computed tomography also revealed the presence of abdominal adenopathy. She underwent resection of the distal jejunum and ileum. The anatomical and pathological study of the intestinal tissue showed transmural and multifocal infiltration (three lesions of about 3.2 cm in maximum diameter) with intestinal T-cell lymphoma with histopathological features compatible with T-cell lymphoma-associated with enteropathy. There were also signs of fibrinopurulent peritonitis. After surgery, the patient was transferred to the intensive care unit for the management of septic shock. She received 13 days of intravenous antibiotics with good clinical response. She was readmitted to the internal medicine department. The immunophenotype showed positivity for CD3, CD7, and CD30, partial positivity for CD2, CD4, and TIA1, and negativity for CD20, CD5, CD8, and CD56. Ki-67 was elevated consistently with a high proliferative index. Intravenous calcium and magnesium supplementation were eventually switched to oral supplementation and oral feeding was started. The patient refused oral anticoagulation and treatment for the lymphoma. She was discharged from the hospital 3 months after admission.
pmc-6386336-1	A 40-year-old male presented with the appearance of skin lesions on his face during the past two months. Past medical history of diabetes mellitus was noted for him without any genetic disorder. On clinical examination, two skin-colored dome shaped firm masses were noted with each size of 10×5mm and 5×5mm, respectively. The larger lesion showed surface ulcerations. With suspicion of basal cell carcinoma (BCC) for both lesions, excisional biopsy was performed and sent for pathological study including hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining for S-100, neuron specific enolase (NSE), smooth muscle actin (SMA), and desmin markers. Histopathological results confirmed the BCC, nodular type, for the larger one (). H&E stained sections of smaller lesion showed epidermis with unremarkable changes. The dermis displayed a well circumscribed, non-encapsulated lesion composed of epithelial and mesenchymal components. The epithelial component consist of distorted and hyperplastic pilosebaceous units with prominent sebaceous glands (). The mesenchymal component mainly showed myxoid and fibrillary appearance containing elongated and wavy spindle cells arranged in fascicles resembling neurofibroma (). Further immunohistochemical study for confirmation of neural mesenchymal stroma was done. Fibrillary mesenchymal componenets express S-100 marker (), while neuron specific enolase, smooth muscle actin, and desmin were negative (). Based on the results of H&E staining and IHC, the diagnosis of neurofollicular hamartoma was confirmed. Neurofollicular hamartoma itself is a benign tumor and treatment was achieved by local excision. The BCC lesion was demarcated and small in size which was surgically removed without further topical treatment or radiotherapy.
pmc-6386643-1	A 44-year-old male patient was admitted to our Vascular Surgery Department. In 2001, the patient was in a traffic accident, resulting in a blunt injury to the chest and pelvis. This, presumably, was the mechanism of development of an aneurysm of the aortic arch. In 2012, on the plane X-ray of the chest, an abnormal mass lesion was found, but computed tomographic (CT) verification was not performed due to unknown reason. In 2014, the patient was hospitalized in our department when we confirmed the diagnosis of the aortic arch pseudoaneurysm ( ). CT imaging identified a giant pseudoaneurysm with maximum size 136 × 72 mm. The size of posterior aortic arch wall defect was 28 mm. There were no signs of aortic dissection. We performed an operation—the elimination of the aortic arch pseudoaneurysm and posterior wall tear and false aneurysm in the mediastinum without the use of cardiopulmonary bypass. The position of the patient was on hs back with his left hand fixed above the head. Under total anesthesia, through the L-shaped median sternotomy and left 5th intercostal thoracotomy, we identified and extracted the ascending aorta, aortic arch, left common carotid and subclavian arteries and mid part of descending aorta ( ). The brachiocephalic trunk was unable to mobilize because it was intimately fused with the anterior wall of the false aneurysm. Therefore, the right subclavian artery was controlled. A temporary bypass (TB) shunt of 20 mm between the ascending and descending aorta was created. In addition, from this bypass an anastomosis with a bifurcation prosthesis for temporary blood supply to the brachiocephalic trunk and left common carotid artery was formed. The first branch of the bifurcated bypass was anastomosed to the right subclavian artery, and the second connected through cannulation to the left carotid artery. The bloodstream was allowed to run through all temporary shunts. The ascending aorta was clamped distal to the shunt, and the descending aorta was clamped proximal to the shunts. Single clamps were placed on the brachiocephalic trunk, left carotid, and left subclavian arteries. Then, a longitudinal aortotomy was made on the front wall of the aortic arch. On the back, the aortic wall was detected, with the defect (with smooth edges, 35 × 20 mm) leading into the cavity of the giant pseudoaneurysm, which was partially filled with old thrombotic material. The posterior aortic wall defect was closed with a Dacron patch. The anterior aortic wall was restored by closing the incision in the aortic wall, with Teflon felt reinforcement. Blood flow was sequentially restored in the aorta and its branches ( ). During the entire operation, blood pressure on the right brachial and femoral artery did not flow below 85 and 90 mm Hg. The duration of operation was 480 minutes. The duration of anesthesia was 680 minutes. Total blood loss was 1,500 mL, with approximately 700 mL from aneurysm cavity. There were no complications after surgery. On the first day after operation, a right-sided pneumothorax was diagnosed, which was treated with active drainage. On the second day, the patient was extubated. An additional drainage to the left pleural cavity was implanted on the fifth day due to persistent left-sided limited pneumothorax. The patient was discharged in good condition on the 19th day after the operation. CT scan at 8 months has shown a persistently closed defect ( ). The size of aneurysm became two times less during 8 months of observation.
pmc-6386645-1	A 16-year-old girl presented with a history of intermittent colicky left lumbar pain. The acute episodes of pain were related to excessive hydration, physical activity, or diuretic drinks. There was no history of urinary tract infection or hematuria. Laboratory urinary tests revealed normal values. Ultrasonography showed dilatation of the left renal pelvis and proximal ureter, with normal renal parenchymal thickness and no calculus; an abdominal situs inversus. A computed tomography confirmed the abdominal situs inversus, and described left ureterohydronephrosis, and left retrocaval ureter. The anteroposterior renal pelvis diameter (APD) was 20 mm and the proximal ureter had a diameter of 18 mm; parenchymal index was normal ( ). As the patient was symptomatic, she was taken into surgery. We used the laparoscopic transperitoneal approach. After induction of general endotracheal anesthesia, a nasogastric tube and a Foley's catheter were inserted. The patient was placed in a modified flank position (45 degrees right lateral decubitus position) with overextension. A 5 mm umbilical port was placed for the 30-degree laparoscope, using an open technique. Two additional 5 mm ports were carefully placed. The line of Toldt's was incised and the left colon was retracted medially to permit access to the renal and retroperitoneal space. Dissection was carried using blunt and sharp instruments, exposing the renal pelvis, precaval dilated ureter, preureteral segment of the IVC, and postcaval ureter. After mobilizing the retrocaval ureteral segment, no intrinsic stricture was noted. The ureter was transected at the most caudal point of the dilated segment, mobilized, uncrossed, and placed lateral to IVC. After spatulation of the distal ureter and antegrade placement double-J ureteral stent (Charrière 4.7) we performed a ureteroureterostomy over a using a 5–0 monofilament, resorbable suture ( ). An intraperitoneal drain was placed close to the anastomosis. Operative time was 150 minutes; no significant blood loss was noted. The postoperative course was uneventful; the lumbar drain was removed on the 2nd postoperative day. The girl was discharged home after 5 days. The double-J stent was removed after 5 weeks. During a 20-month follow-up the patient was symptom-free. Ultrasonographic re-evaluation showed marked decrease of APD (7 mm).
pmc-6386793-1	A 43-year-old woman presented for evaluation of infertility on 29 th January 2018 at the Centre for Reproductive and Genetic Health, London. She had secondary infertility for one year and had previously had a first trimester miscarriage, which was managed conservatively. Her medical history was unremarkable. Her ovarian reserve test showed a total antral follicle count of 6, anti-Mullerian hormone 4.7 pmol/l, follicle stimulating hormone 10.10 IU/l and oestradiol <250 pmol/l. Her male partner was 33 years old. His medical history was unremarkable and his semen analysis was normal. The couple was counseled. The patient underwent two consecutive cycles of controled ovarian stimulation to optimize the yield of embryos sent for PGT-A testing. An antagonist protocol was prescribed with Fostimon® 225 IU and Merional® 225 IU (IBSA, Italy). Vaginal egg retrieval was carried out 37 hr post 10,000 IU of Pregnyl (MSD, UK). On the first cycle, a total of eight oocytes were collected, seven were mature and three exhibited normal fertilization at 16–18 hr post intracytoplasmic sperm injection (ICSI). A total of three top-quality embryos were frozen using the vitrification techniques on day 3 of embryo development. Embryo vitrification was performed using Kitazato vitrification kit with the use of high concentrations of cryoprotectants and ultra-rapid cooling to avoid detrimental ice crystal formation (). On a subsequent cycle, a total of four eggs were collected all of which were mature and three fertilized following ICSI. On day 3 of embryo development, the frozen embryos from the previous cycle were thawed and all cultured to the blastocyst stage simultaneously. From the frozen thawed cohort of embryos, one embryo reached the blastocyst stage on day 6, while from then fresh cohort one embryo formed a blastocyst on day 5 of development. The blastocyst is an advanced stage of embryo development where the embryo differentiates into two cell lines, the inner cell mass and the trophectoderm, and forms a fluid filled cavity (Blastocoel). It is a prerequisite to culture embryos to the blastocyst stage prior to trophectoderm biopsy. The unit policy is to only perform blastocentesis on half the embryos reaching the blastocyst stage for quality control. Therefore, the day 5 developing blastocyst was subjected to blastocentesis using a microinjection pipette prior to trophectoderm biopsy (). A minimal invasive micro-puncture was performed between two junctions of cells, the fluid was aspirated and then expelled into a 0.2 ml Eppendorf tube. The tube was immediately placed on an ice rack and stored in a −80 °C freezer until analysis. Trophectoderm biopsy was then performed immediately using a non-contact 1.48 μm diode laser (RI, Cornwall, UK) with a total of 5–8 trophectoderm cells removed. Prior to blastocoelic fluid aspiration and trophectoderm biopsy, the blastocyst was removed from the embryoscope slide dish and approximately 15–20 μl of spent culture media was collected using a sterile individually wrapped 20 μl Gilson pipette. The collected media were expelled into a 0.2 ml Eppendorf tube and immediately placed on a cold rack and stored at −80°C until further analysis. The blastocyst was vitrified post biopsy using Cook blastocyst vitrification media (Cook, Sydney). All three samples containing DNA and a negative control were sent to our genetic provider, Reprogenetics UK, where genetic analysis was performed using next generation sequencing (NGS). The blastocoel fluid sample and 10 μl of the spent media sample were each subjected to a modified version of MDA (Qiagen, UK) using a protocol developed at Reprogenetics specifically for the purpose of amplifying DNA from blastocoel fluid and spent media samples (Babariya and Wells, unpublished). The amplified products were run on a 1% (w/v) agarose gel to check for amplification success. Thereafter, Nextera DNA kit (Illumina, UK) was used to prepare libraries from successfully amplified samples followed by 75 bp paired end sequencing on a MiSeq (Illumina). Unfortunately, the blastocoel fluid sample resulted in suboptimal amplification and was not subjected to NGS. The sequencing data was analyzed using an in-house custom algorithm to determine the chromosomal copy number. The trophectoderm biopsy results were euploid for both the embryos. Analysis of cell-free DNA in the corresponding embryo culture media yielded concordant results, indicating that both of the embryos were euploid. The patient had a 3D saline infusion sonohysterography on day 12 of the cycle, which revealed a normal uterine cavity. She was advised to take Primolut® (Bayer Schering Pharma, Germany) 5 mg twice daily from day 14 of the cycle until day 25 with Buserelin® (Sanofi-Aventis, Germany) from day 21 as per manufacturer’s instructions. Buserelin was stopped once luteal phase support was commenced. She had a baseline scan on day-1–3 to assess the endometrium and ovaries. Progynova® (Bayer, UK) 2 mg three times daily orally and 2 mg twice daily vaginally was prescribed on day-3 of the withdrawal bleed. She was advised to have a repeat transvaginal scan 12 days later to assess endometrial thickness. Once the endometrium was >7 mm in thickness and had a triple line on ultrasound, luteal support was commenced and embryo transfer was booked 6 days later. Luteal support for cryopreserved embryo transfer cycles included Utrogestan® (Besins, Belgium) 200 mg three times daily orally, intramuscular Lentogest (Institut Biochemique SA, Switzerland) three times per week and Crinone® 8% (Merck Serono, UK) twice a day per vaginam. These were continued until 10 weeks of pregnancy. The suitable blastocyst was warmed on the day of embryo transfer using Cook Warming Kit (Cook, Sidney). The patient was instructed to perform a urinary pregnancy test 16 days later. As the urinary HCG test was positive, the patient was advised to come to the unit for serum HCG. Her serum hCG was 1312.0 IU/l. Subsequently, scans at 6 weeks and 8 weeks of gestation confirmed a viable intrauterine singleton pregnancy with normal foetal development. At the time of the write up of the case report, the patient was 20 weeks without any reported foetal or obstetric concerns. This study was approved by the IRAS 214276. This report is based on a finding of the ongoing prospective study.
pmc-6386959-1	Patient 1 was a 27-month-old boy with persistent macrohematuria, proteinuria (1300 mg/L), active sediment, and normal renal function. His older sister and his non-consanguineous Lithuanian parents were healthy, with no family history of kidney diseases (a). Post-infectious glomerulonephritis was excluded. Due to the initial suspicion of an infection and normal renal morphology on ultrasound examination, a cystoscopy was performed, which revealed hemorrhagic cystitis. However, common causes of hemorrhagic cystitis in childhood [,], such as cytomegalovirus or BK-polyomavirus infection, were ruled out. Consequently, a renal biopsy was performed. Light microscopy and immunohistochemistry (b,c) revealed profound FSGS, IgM-positive deposits, and slight mesangial expansion. Ultrastructurally, the GBM presented with diffuse splitting, thinning, and ruptures (d–f). The podocytes showed foot process effacement, with partial loss of the slit diaphragm (d). These structural changes led to the diagnosis of AS. Hearing and eye evaluations did not reveal any abnormalities. Nephroprotective angiotensin-converting enzyme (ACE)-inhibitor therapy with ramipril was started [,], and the proteinuria slowly decreased from 1300 mg/L to less than 400 mg/L (g). No further macrohematuria was reported.
pmc-6387074-1	A 11-month-old female Italian infant was admitted to our hospital because of three days of fever, vomiting, and worsening of her general conditions. Physical examination revealed a febrile and pale child with a normal neurological status. Axillary temperature was 40 °C, and the refill time was 2 s. There were no signs of upper or lower airway infections or meningeal involvement. Her weight was 10 kg (50th percentile), her length was 74 cm (50th percentile) and her head circumference was 44 cm (45th percentile). Her growth showed a linear trend from birth, and she reached psychomotor milestones regularly. She was born at term, and she was breastfed until six months. She followed a various and complete diet. There was no history of consanguinity, blood disorders or kidney diseases. The initial work-up showed leucocytosis (white blood cells, 11,620 × 103/µL); normochromic normocytic anemia with hemoglobin values under 2 standard deviation (SD) for age (Hb, 8.6 g/dL); MCV and MCH, normal for her age (MCV 75.9 fl; MCH 24.6 pg); and a mild increase in C reactive protein (CRP, 2 mg/dL). Kidney function was normal (creatinine, 0.21 mg/dL; azotaemia, 20 mg/dL), whereas urine was turbid with 104 leucocytes (UCF), a low-grade proteinuria measured on an extemporaneous sample (100 mg/dL), and urine culture resulted positive for Escherichia coli. Diagnosis of urinary tract infection was made, and intravenous therapy with ceftazidime was started. After eight days, the infant was discharged from our hospital with normal blood exams and anemia was interpreted as a transient finding during an acute infective process. The child missed her first follow-up visit, and 17 months later, when she was 28 months old, during an occasional visit a mild-moderate proteinuria with a mixed tubular-glomerular pattern was detected (187 mg/dL). On a 24-h urine sample, an elevated proteinuria/creatininuria ratio was found (patient’s ratio: 2, normal values <0.2) with proteinuria (60 mg/dL) and creatininuria (30 mg/dL). A blood exam revealed macrocytosis (MCV 98.5 fl) in the absence of anemia (Hb 12.4 g/dL). Renal ultrasound showed no anomalies of kidneys or the urinary tract. However, she presented oral aphthous ulcers, vulvar hyperaemia, and abnormal movements of buccal rhyme. We finally dosed peripheral blood levels of folate and vitamin B12, finding a severe vitamin B12 deficiency (0.1 pg/mL; normal range values 180–914 pg/mL). Vitamin B12 was analyzed using Electrochemiluminescence ImmunoAssay (Roche Diagnostics GmbH, Mannheim, Germany) and the low value was identified using dilution methods. The combination between severe B12 deficiency and proteinuria was strongly suggestive of IGS. summarizes the clinical and laboratory findings at admission and during follow-up: normal values for age are shown; we decided to replace vitamin B12 intramuscularly (IM). A first administration of cyanocobalamin (200 mcg/day) IM for two consecutive days was given, followed by administration of 100 mcg/day for seven days; the maintenance dose consisted of 100 mcg a week for one month (four doses overall) followed by 100 mcg administered monthly. The first vitamin B12 dosage was made after one week and after four months from the beginning of the therapy. Vitamin B12 levels increased rapidly: one week later, vitamin B12 values were normal (622 pg/mL), anemia resolved (Hb 12.8 g/dL; MCV 94.1 fl; MCH 31.7 pg), while mild proteinuria persisted (70 mg/dL). At the 4-month follow-up of therapy, vitamin B12 levels were still in the normal rage (169 pg/mL), hemoglobin was normal (Hb 13.5 g/dL), urine extemporaneous proteinuria levels were 60 mg/dL, and there was no macrocytosis (MCV 75.8 fl). Considering the clinical and laboratory findings, i.e., macrocytosis and persistent proteinuria with a severe lack of vitamin B12, the child was assessed for IGS. DNA was extracted from peripheral blood of the patient, and sequencing of the coding regions and of the exon–intronic junction of the AMN gene was performed. The variants identified in the proband were analyzed in the parents through Sanger sequencing. Sequence analysis showed the presence of a novel intronic variant c.513+5G>A of AMN, never before described in the literature, that was in compound heterozygosity with the known pathogenetic variant c.1006+34_1007-31del. Indeed, analysis extension to the parents revealed the presence of variant c.1006+34_1007-31 in the father and c.513+5G>A in the mother. Clinical information and blood samples were obtained after approval from the Ethics Committee (PED-2018-18, 15 September, 2018) of the Umbria Region with signed informed consent by both parents. Parents also signed the consent for the publication of this case report.
pmc-6387308-1	Case 1: A 19-year-old previously healthy gravida 3 para 2002 emigrated to the U.S. at 25 weeks of gestation. During the 20th week of gestation, she and her family members (including her spouse) all experienced a maculopapular rash, conjunctivitis, fever, and headache; she and her spouse had unprotected intercourse through the first and second trimester. Approximately two weeks after their symptoms resolved, she and her spouse traveled by bus and foot across Honduras, Guatemala, and Mexico. At the time of initial presentation to care in the U.S. at 28 weeks’ gestation, she had positive ZIKV IgM serology and a positive serum NAT. Initial fetal ultrasound with neurosonography was significant for cerebral ventriculomegaly (20–25 mm) with dangling choroid, prominent 3rd ventricle, and a widened cavum septum pellucidum; microcephaly was never observed. An amniocentesis was performed, and showed a negative NAT for ZIKV with no evidence of small or large structural chromosomal variations by CMA; the TORCH panel was also negative. Repeat maternal serum testing for ZIKV by NAT was persistently positive until 38 weeks’ gestation, when she became NAT seronegative; at 34 weeks ZIKV serology (IgM) became negative. At 38 weeks and two days gestation (38w2d) an indicated cesarean was performed for oligohydramnios with fetal breech presentation. At delivery or postnatally, maternal and/or neonatal testing for ZIKV in serum, amniotic fluid, CSF (neonatal), and urine was negative. Neonatal and infant findings including ophthalmic exam and abnormal postnatal brain and head imaging are depicted in . Key and persistent postnatal imaging findings include ventriculomegaly with absent cavum septum pellucidum, prominent third ventricle without obstruction at the level of the foramen of Monro, and diffuse white matter and corpus callosum volume loss with multiple sub-centimeter subependymal nodules along the lateral ventricles. On ophthalmic exam, the infant had bilateral colobomatous lesions consistent with congenital Zika syndrome. The infant has been readmitted on multiple occasions during the first six months of life for hypotonia and epileptic encephalopathy with infantile spasms and modified hypsarrhythmia requiring neuroleptic medications with global developmental delay.
pmc-6387308-2	Case 2: A 24-year-old previously healthy gravida 3 para 0200 arrived in the U.S. at 11 weeks of gestation, after emigrating from Cuba through Central America and Mexico. She and her husband denied any symptoms consistent with a flavivirus infection; they had unprotected intercourse through the first and early second trimester. She was seen for her initial prenatal visit at 15 weeks’ gestation, and testing for ZIKV by serum and urine NAT and IgM were initially and persistently negative. A fetal ultrasound with neurosonography performed at 23 weeks showed no microcephaly but was significant for borderline asymmetric ventriculomegaly, with a thin cortex and dolichocephaly, but absence of microcephaly; amniocentesis was declined. Serial fetal ultrasound imaging throughout pregnancy was performed secondary to initial 23-week ultrasound findings. At 37 weeks, induction of labor was undertaken for intrahepatic cholestasis of pregnancy and a cesarean delivery was performed for fetal intolerance of labor. Neonatal findings were significant for craniofacial dimorphism with a cleft palate, microopthalmia, and hypertonia with asymmetric EEG findings consistent with abnormalities in the right hemisphere. She developed neonatal seizures and failed her newborn hearing screen. Representative neonatal and infant brain imaging are shown in , and include callosal dysgenesis with asymmetric ventriculomegaly, a thin cortex, and dolichocephaly with bilateral optic nerve hypoplasia. There were no patellar nor limb abnormalities. Neonatal and infant ZIKV and TORCH laboratory testing was negative. No evidence of small nor large structural chromosomal variations by CMA was found, and whole exome sequencing (WES) failed to reveal neither pathogenic nor likely pathogenic variants in disease genes related to the clinical phenotype. A novel de novo heterozygous c.3667G>C (p.V1223L) variant in the MED12 gene (located on ChrX:70349255) of unknown clinical significance (VUS) was found. This female infant has clinically persistent neurologic disease and early developmental delay.
pmc-6387476-1	A 71-year-old female with a pulmonary metastasis from primary sigmoid colon cancer presented for video-assisted thoracoscopic LUL lobectomy. She underwent resection of sigmoid colon cancer (StageIIA T3N0M0) five years previously. She did not receive adjuvant chemotherapy. Recent computed tomography scan revealed a mass in the left upper lobe of the lung, and she was admitted to undergo video-assisted thoracoscopic LUL lobectomy. She had a history of hypertension and osteoporosis, treated with raloxifen, alfacalcidol, fexofenadine hydrochloride, pseudoephedrine and esomeprazole magnesium hydrate. She smoked two packs of cigarettes per day for 45 years. Physical examination on admission was unremarkable. Preoperative electrocardiogram showed sinus rhythm with an incomplete right bundle branch block. After placement of an epidural catheter between the fifth and sixth vertebrae, general anesthesia was induced with remifentanil and propofol. Tracheal intubation was accomplished using rocuronium bromide. Combined epidural and general anesthesia was maintained with remifentanil, desflurane and ropivacaine. The LUL lobectomy proceeded without difficulty with an operating time of 157 min. No arrhythmias or severe hypotension were detected during the surgery. She was transferred to a general ward after extubation in the operating room. The postoperative course was uncomplicated with no episodes of atrial fibrillation on the first postoperative day. On the evening of the second postoperative day, she was seen to lean suddenly to the left after urinating. She developed left hemiparesis, right conjugate deviation and dysarthria. She underwent emergency magnetic resonance imaging after immediate removal of the epidural catheter. Cerebral magnetic resonance angiography revealed cessation of blood flow in the right internal carotid artery (Fig. ). An acute cerebral infarction was diagnosed and she was transferred to another hospital to receive intravascular therapy. Initially, 4000 units of heparin were given intravenously. Four hours after onset of arterial occlusion, extensive dark brown thrombi were removed though the intravascular catheter, and cerebral perfusion was reestablished. She received protamine at the end of procedure. Anticoagulation therapy was delayed until postoperative day 21 because a minimal hemorrhagic infarction developed. She recovered with only mild paralysis of the left upper extremity and was transferred to a rehabilitation facility on postoperative day 37.
pmc-6387511-1	A 25-year-old female with poorly controlled type 1 diabetes mellitus presented to hospital for the second time in two weeks with recurrent, antibiotic-refractory left sided facial swelling and pain complicated by diabetic ketoacidosis (DKA). There was no history of antecedent dental manipulation. Two weeks prior, she was seen in an ambulatory clinic for the same symptoms and took a three-day course of amoxicillin-clavulanic acid 875/125 mg twice daily but was admitted to hospital three days later for DKA. During this index hospitalization, her diagnosis was correlated radiographically and presumed to be sinusitis complicated by DKA. A two-day course of ceftriaxone 2 g intravenously once daily and vancomycin 1 g intravenously twice daily was administered before transitioning to doxycycline 100 mg twice daily for an additional ten-day course. She returned to hospital a mere ten days later with progressive left-sided facial swelling and was found to meet biochemical criteria for DKA. She was afebrile and hemodynamically stable but had profound left periorbital edema with necrotic lesions along her left maxillary region and forehead. Three sets of blood cultures, each consisting of an aerobic and anaerobic bottle pair (20 mL per bottle), were drawn before any further parenteral antibiotics were given remained negative after 4-days of incubation in a BacT-Alert automated system (bioMérieux, Laval, Quebec). HIV serology was negative. Comparison of a repeat computed tomography (CT) scan of her sinuses with CT images performed during her prior hospitalization demonstrated improved aeration of the left maxillary sinus but progressive left facial soft tissue swelling complicated by subcutaneous emphysema. Subsequent CT-angiogram of the neck revealed an internal maxillary artery occlusion. Although initial nasal rhinoscopy revealed normal appearing sinus tissue, surgical debridement to the epicranial aponeurosis revealed necrotic tissue with poor vascular supply but no microbiological diagnosis. She was started empirically on parenteral therapies of piperacillin-tazobactam 3.375 g every six hours, vancomycin 1250 mg every twelve hours and liposomal amphotericin B at 7.5 mg/kg once daily before transfer to a tertiary care center for further surgical consultation. The ischemic changes on her face was originally thought to be secondary to the internal maxillary artery occlusion from surrounding inflamed tissue. Given the extent of her rhino-orbital disease, she underwent surgical debridements. Her timeline is outlined in Fig. . Original tissue cultures, including anaerobic, fungal and acid-fast bacilli cultures set-up under various growth, differential and selective media for pathogen identification were negative. Four subsequent deeper debridements were done, which extended down to the sternocleidomastoid muscle and up to the auditory canal and as deep as the skull base. Histopathology from biopsied tissue and bone from these sites revealed pauci-septated, ribbon shaped elements with liquefactive skin necrosis consistent with mucormycosis (Fig. a and b). Microbiological 18 s RNA sequencing ultimately identified Rhizopus oryzae as the causative organism. Her hospitalization was complicated by kidney injury secondary to hypovolemia and amphotericin B, necessitating intermittent hemodialysis but she subsequently recovered her renal function. Due to disfiguration from extensive debridement, she underwent a facial skin graft reconstruction after achieving surgical care of her invasive fungal infection. She was transitioned to isavuconazole for three months and then to posaconazole which she continues indefinitely.
pmc-6387536-1	A 36-year-old woman was referred to the endocrine surgeon with a neck mass that gradually enlarged over a year. This mass was associated with dysphagia and complicated by skin sinus formation. There was no prior or family history of thyroid disease. Laboratory tests showed no evidence of thyroid hyper or hypo function. Physical examination revealed a central neck skin sinus with a serosanguinous discharge (Fig. a). The thyroid gland was non-tender, diffusely enlarged, and extending bilaterally and retrosternally, mainly on the left side, with no cervical lymphadenopathy detected. Computerized tomography (CT) scan demonstrated a diffuse enlargement of the thyroid gland with skin infiltration, heterogeneous density and macrocalcification. The thyroid enlargement caused tracheal and esophageal compression and displaced neck vasculature laterally (Fig. b). Brain, chest, abdomen and pelvis CTs did not show any metastasis. FNA from the right thyroid lobe was interpreted as PTC. The decision was to go for total thyroidectomy with central neck dissection. Intraoperatively, the thyroid gland was extremely adherent to the surrounding structures with infiltration of the skin, strap muscles and both carotid sheaths, and extensively adherent to the esophagus and trachea. Consequently, only debulking thyroidectomy (isthmectomy) was performed along with sinus track excision and sampling of the central lymph node compartment. The thyroid specimen was received fragmented and consisted of multiple pieces of firm brown-tan tissue, measuring 5.5 × 5 × 0.4 cm in aggregate. Also received was an ellipse of skin and a “central” lymph node, measuring 5x1x0.7 cm and 1.5 × 0.8x4cm, respectively. Microscopic examination of sections from the thyroid gland revealed a classical PTC (Fig. a). In addition, there were cells with eosinophilic cytoplasm and mild to moderately pleomorphic nuclei, some showing irregular contours or grooves, admixed with inflammatory cells including numerous eosinophils. These cells were seen in extensive sheets replacing 60–70% of the resected thyroid tissue as well as focally within the neoplastic papillary cores (Fig. b). Similar cell sheets were seen in sections of the skin and lymph node. Immunohistochemically, the papillary carcinoma stained positively for pan cytokeratin (CK) (Fig. c) and cytokeratin 19 (CK19) (data not shown), while the infiltrating mononuclear cells showed diffuse, strong reactivity for CD1a (Fig. d), CD43, S100 protein and were negative for myeloperoxidase, LCA and HMB45 immunostians (data not shown). The Ki67 proliferation index in these cells was around 60% (data not shown). The final diagnosis was synchronous PTC and LCH involving thyroid, overlying skin and cervical lymph node. Paraffin blocks including both the PTC and the LCH were manually macrodissected. DNA was automatically extracted and purified by QIAcube (Qiagen) from the two lesions separately using QIAamp DNA FFPE, while the concentration and purity of extracted DNA was assessed by Epoch-Bioteck. BRAF mutations were investigating using Easy BRAF kit (Diatech) that detects BRAF codon 600 mutations by real-time PCR (Rotor-Gene). DNA was assessed by analysis of the reaction controls (water, BRAF positive control) and analysis of BRAF control mix. The two DNA samples extracted from the two different lesions passed the assessment of DNA, and then were analyzed to search for mutations. Mutational analysis of BRAF for the DNA extracted from PTC and LHC revealed V600E and V600K mutations, respectively (Fig. ). The postoperative course was uneventful. The patient received palliative chemotherapy, at her home country, that consisted of Etoposide with Prednisone. After twelve months of follow-up, the patient is in a stable clinical condition.
pmc-6387537-1	A 69-year-old previously well Sinhalese man presented with lethargy, loss of appetite, vomiting, and altered behavior that lasted for a week. One week ago, he was apparently well but his family members noticed that he was becoming increasingly lethargic. For an initial few days, they were reluctant to seek medical advice; however, with the onset of new behavioral changes, it was decided to bring him to the hospital. He was a business executive and he had never taken alcohol or smoked tobacco in his life. There was no significant family history of note. On examination, his body mass index was 19 kg/m2. His skin temperature was 37.8 °C. He was confused, with a Glasgow Coma Scale (GCS) of 13/15 and showed evidence of mild dehydration. He had normal skin appearance with normal axillary and pubic hair distribution. His pulse rate was 90 beats per minute and blood pressure was 99/60 mmHg. A cranial nerves examination was normal. Both tone and reflexes of his upper and lower limbs were normal except muscle power of grade 4. Gait assessment was not performed due to low GCS. The rest of the examinations including respiratory and abdomen were unremarkable. The initial laboratory results were as follows: serum sodium 104 mmol/L, serum potassium 4.3 mmol/L, white cell count 8.8 × 109/L, hemoglobin 9.9 g/dL, platelet count 272 × 109/L, serum creatinine 89 μmol/L, and normal liver function tests. Plasma and urinary osmolalities were 251 mOsm/kg and 305 mOsm/kg respectively. His urinary sodium level was 158 mmol/L. Blood sugar level and serum triglyceride levels were within normal range. Although the duration of symptoms was more than 48 hours, the presence of severe hyponatremia necessitated serum sodium correction with intravenously administered 3% saline. After the first 150 ml bolus of 3% saline, his serum sodium level had risen to 115 mmol/L and there was a slight improvement in his orientation. Since his urine output was satisfactory with stable hemodynamic parameters, normal saline 100 ml/hour was continued. On the second day of admission, his GCS further dropped to 12/15. Repeat serum sodium levels further dropped to 112 mmol/L. Although a rapid correction of serum sodium level is associated with osmotic demyelination syndrome, the presence of severe symptomatic hyponatremia required correction with another 3% saline 150 ml bolus. Repeat serum sodium levels became 120 mmol/L and he showed a slight improvement in GCS of 14/15. Meanwhile, due to fluctuating conscious levels, non-contrast computed tomography (CT) brain was performed. This revealed a mass lesion in the region of optic chiasma and the radiology team suspected an aneurysmal dilation. A CT cerebral angiography was then performed which confirmed the presence of a pituitary macroadenoma (Fig. ). A pituitary hormone profile was then carried out and the results were as follows: free tetraiodothyronine (T4) 8.21 pmol/L (10–68), thyroid-stimulating hormone (TSH) 1.5 mIU/L (0.4–4.6), luteinizing hormone (LH) 1.13 mIU/ml (1.2–7.8), follicular-stimulating hormone (FSH) 1.65 mIU/ml (1.55–9.74), and prolactin 22 ng/ml (3.7–17.9). His morning (9 a.m.) serum cortisol level was 1.49 μg/dL (4.3–22.4). The diagnosis of a nonfunctioning pituitary macroadenoma with secondary hypoadrenalism and hypothyroidism was made. Daily intravenously administered hydrocortisone 50 mg 6 hourly with levothyroxine 75 μg was commenced. After 4 days of replacement, his serum sodium level became stable to around 133 mmol/L and there were marked disappearances of lethargy and fatigability. The intravenously administered hydrocortisone was then replaced with orally administered hydrocortisone and after 1 week of treatment, he had further improved and was able to resume his daily activities as before. He was then referred to the neurosurgical unit for further care. An endoscopic excision of the pituitary tumor was carried out under general anesthesia and later tumor histology revealed pituitary oncocytoma. The preoperative period was covered with intravenously administered hydrocortisone 50 mg 6 hourly and the same dose of levothyroxine. Following surgery, he was discharged with levothyroxine 75 μg and orally administered hydrocortisone 15 mg two times daily. Six weeks after discharge, his general condition was stable and his serum sodium level was 133 mmol/L. His serum T4 level was 34 pmol/L and serum cortisol level was 15 μg/L. Since hormonal levels were well within normal range, the same drug doses were continued. At 3-month clinic and 6-month clinic, visits were unremarkable except the need for reduction in hydrocortisone dose to 10 mg twice daily due to development of impaired blood glucose levels.
pmc-6387549-1	A 9-year-old Japanese girl with a known history of non-hereditary GDD presented with pain and deformity in the left thigh after a minor fall. The GDD was diagnosed by the facial bone developmental dysplasia and genetic examination when she was 3 years old. She had a history of multiple fractures of various sites, such as bilateral tibia, fibula, thoracic vertebrae, cervical vertebrae, and coccyx. All previous fractures had been successfully treated conservatively without complications. Her bone mineral density (BMD) measured using dual-energy X-ray absorptiometry at the previous hospital 2 years ago was lower than the age-adjusted average; her spine BMD was 0.493 g/cm2 and T-score was − 5.9. At the initial radiologic examination, a displaced transverse fracture (32-D/4.1 in AO Pediatric Comprehensive Classification of Long Bone Fractures (AO-PCCF) []) in the mid-shaft of left femur was observed (Fig. ). Repositioning of the fracture fragments was not successful using skin traction with external hanging weights. Thus, the patient underwent a closed reduction and external fixation by using a unilateral fixator system (Hoffmann II®, Stryker Corporation, Kalamazoo, MI) with 5-mm non-hydroxylapatite-coated half pins under general anesthesia 6 days after the injury (Fig. ). The radiograph obtained at the 12-week follow-up showed a solid bony union at the fracture site, and the fixators were removed (Fig. ). The patient was allowed to initiate and gradually advance weight bearing. At 25 weeks after the initial surgery, she suddenly felt severe pain in her left thigh while she was walking and was unable to walk further. Radiological examinations revealed another fracture in the left femur (32-D/4.1 in AO-PCCF) at one of the half-pin insertion sites (Fig. ). She underwent an external fixation again. After this operation, the patient sustained a refracture (32-D/4.1 in AO-PCCF) at the same fracture site, followed by a supracondylar fracture (33-M/3.1 in AO-PCCF) at a distant site of the femur (Fig. ) and two consecutive fractures at the half-pin insertion sites (Fig. ). The supracondylar fracture occurred without any triggering activity before beginning weight-bearing exercise. The supracondylar fracture was successfully treated conservatively, but she sustained two more consecutive diaphyseal fractures (32-D/4.1 and 32-D/4.1 in AO-PCCF) at the half-pin insertion sites (Fig. ). She eventually underwent a revision surgery for the diaphyseal fractures with an Ender nail (Ender nail®, MIZUHO Co., Ltd., Tokyo, Japan). Open reduction was not easily achieved owing to the fracture deformity and growing callus. Only one nail could be passed through it because the medullary canal was significantly narrowed due to diaphyseal sclerosis associated with GDD (Fig. ). After this operation, the patient started early functional rehabilitation and was allowed to progress gradually to partial weight bearing following pain relief. The radiographs at 5-month follow-up showed a solid bony union at all the fracture sites, and the Ender nail was removed (Fig. ). Three months after the implant removal, the patient maintained her ambulatory status without further refractures.
pmc-6387695-1	The patient is a 15-year-old competitive male swimmer with a history of bilateral arthroscopic subacromial decompression within the preceding year. The patient continued regular follow-up with the senior author until he reached maximal medical improvement (MMI) from these procedures. One week following this visit, the patient suffered a right shoulder dislocation while swimming, which was self-reduced. He presented to the clinic 3 days following the injury. At this time, he reported mild pain (3/10), and his self-reported functionality was less than 20% of normal. Upon presentation, the patient was not in acute distress, and there was no obvious deformity of the right shoulder. He reported tenderness to palpation on the bicipital groove and achieved 150 degrees of scaption, 45 degrees of external rotation, and internal rotation to the T10 level. He demonstrated a positive Neer test, Hawkins test, O'Brien's test, and valgus sheer test. He demonstrated a positive anterior load test. He demonstrated a negative posterior load test, belly test, and a lift-off test. An MRI was ordered to evaluate his labrum, which demonstrated a humeral head subluxation with posterior humeral head contusion and Buford complex. Conservative management with physical therapy was recommended at this time. After six weeks of physical therapy, the patient returned for evaluation and noted moderate pain (4/10), function less than 50% of normal, and instability. He was experiencing serious discomfort using a ladder and experienced an episode of shoulder subluxation. His physical examination findings were largely unchanged from his previous visit but exhibited discomfort with apprehension and anterior load examinations. Following examination, his previous MRI was again reviewed. While the official report described a Buford complex, the abnormal-appearing labrum was located more inferior than the typical Buford complex—consistent with an anterior labral tear (). Given his inability to return to sport activities and MRI results consistent with a labral injury, it was recommended that he undergo arthroscopic anterior labral repair due to his lack of progress from conservative management. The patient and his family elected to proceed with operative management. During the procedure, the patient was placed in the lateral decubitus position. Standard anterior and posterior portals were established with an accessory anterior superolateral viewing portal. Diagnostic arthroscopy was significant for complete disruption of the labral tissue between the 3 o'clock and 6 o'clock positions (Figures and , respectively). It was also revealed that there was an articular glenoid cartilage lesion measuring 6 mm × 8 mm anteroinferiorly (). The posterior and superior labrums were intact, and there was no damage to any rotator cuff tendon or the biceps tendon. Before the labral repair, the calcified cartilage layer along the anterior-inferior glenoid, beneath the cartilage flap, was gently debrided and removed with an arthroscopic shaver and an arthroscopic curette (). An arthroscopic biter and shaver were utilized to trim the fibrillated margins of the cartilage tissue. Three 2.4 mm Polyetheretherketone (PEEK) (Arthrex, Naples, FL) SutureTaks were placed at the 6, 4:30, and 3 o'clock positions on the glenoid. A 25-degree right angle suture lasso (Arthrex, Naples, FL) was used to imbricate several millimeters of capsular tissue. The suture lasso was then passed beneath the labrum at the site of each suture anchor and was then subsequently advanced through the fibrous rim of the displaced cartilage flap/GLAD lesion. The Nitinol wire was used to shuttle #2 FiberWire though the cartilage flap, around the labrum, and through the capsular tissues to establish 3 fixation points (Figures and ). A simple knot configuration was tied with sliding arthroscopic Weston knots followed by three alternating half stitches, repeated 3 times, beginning inferiorly at 6 o'clock, progressing superiorly to 4:30 and 3 o'clock. This construct restored tension to the anterior band of the inferior glenohumeral ligament, recreated the anteroinferior labral bumper, and effectively reduced the cartilage flap/GLAD lesion to the anterior inferior glenoid (Figures and ). Three months postoperative, the patient reported no pain and 85% of normal function. On physical examination, he achieved 165 degrees of scaption, 65 degrees of external rotation, and internal rotation to the level of T9. At this time, he was instructed to continue physical therapy as per standard institutional protocol. Five months postoperative, the patient suffered a traumatic fall backwards and landed on his outstretched, extended hand. He felt that his shoulder may have subluxed and noted moderate pain with activity (5/10). On physical examination, he achieved 150 degrees of scaption with discomfort, 45 degrees of external rotation with discomfort, and internal rotation to the level of T10. He had discomfort with apprehension, which was relieved with relocation, as well as discomfort with anterior load and shift. An MRI was performed which revealed an intact GLAD lesion repair and labral repair (Figures and , respectively). The GLAD lesion repair remained intact. Given the acuity of the injury, it was recommended that he undergo conservative treatment for one month. The patient was seen one month later at his 6-month postoperative visit and reported no pain and 95% normal function. On physical examination, he achieved 170 degrees of scaption, 50 degrees of external rotation, and internal rotation to the level of T5 without any discomfort. He exhibited no tenderness to palpation and demonstrated a negative Neer test, O'Brien's test, valgus sheer stress, belly press test, anterior load test, and posterior load test. The apprehension test was similarly negative. The patient was instructed to continue with his home exercise regimen.
pmc-6387697-1	A 44-year-old male constructor worker fell down from a 3-storey high building and presented to our Emergency Department. An open fracture of the left talus Gustilo type 3b was visible with an external submalleolar wound of 7 centimetres. Peripheral pulses were present, and the neurological status was intact. Plain film radiographs showed a posterior dislocated distal fibula fracture, a comminuted vertical shear fracture of the medial distal tibia and a talus fracture (). In order to obtain a precise diagnosis and plan surgery, a computed tomography (CT) scan of the ankle was performed, showing a dislocated distal fibula in contact with the posterior medial part of the talus, a multifragmentary talus fracture with a sagittal split and a separation between the body and neck and an AO 43-B2 distal tibia fracture (). Considering an open fracture with an irreducible external malleolus, immediate surgery was performed. We used the open wound that extended from the proximal part of the external malleolus fracture to the cuboid bone to approach the fractures from the lateral side. First, the distal lateral malleolus was extricated as it was located between the distal tibia and posterior talus and fixed with two axial 2.2 Kirschner wires. The Chaput fragment was also stabilized with a single 1.2 Kirschner wire. These three wires were cut to the desired length, bent, and impacted into the bone. We then approached the medial aspect of the ankle, through an incision extending from 5 cm above the tip of the medial malleolus to the medial tuberosity of the navicular bone. Reduction and fixation of the talus with two K-wires and two partially threaded screws were accomplished. The quality of reduction was controlled on both medial and lateral approaches. Osteosynthesis of the pilon fracture was performed with a reconstruction plate. Intraoperative testing did not reveal syndesmotic instability. Postoperatively, a short leg cast was applied for a period of 12 weeks. Rehabilitation protocol consisted in 6 weeks of nonweight-bearing and a progressive weight-bearing starting from week 7. No acute complication was observed. At 6 months of follow-up, the fractures were consolidated. The X-rays showed an anatomical reconstruction, with no sign of talar necrosis (). Passive flexion/extension of the ankle was limited to 20/0/0. The patient was able to walk for limited periods and distance only with adapted shoes and needed a daily pain medication intake. He was unable to regain his previous working status. Resuming sport activities was not possible. At one year postoperative, the patient developed an invalidating partial necrosis of the talus and pilon () that eventually required an ankle-hindfoot arthrodesis 14 months after the accident.
pmc-6387706-1	A 53-year-old woman with small stature and dysmorphic features consistent with TS, not previously diagnosed with diabetes, presented to the endocrinology clinic for evaluation of episodes of hypoglycemia <20mg/dl with transient loss of consciousness. She was admitted to the inpatient service and underwent a controlled 72h fast. After 64h, she developed hypoglycemia to the low 30s mg/dl with mild neuroglycopenic symptoms (emotional outbursts). Biochemical workup showed unsuppressed insulin levels (1.2mIU/L), markedly elevated proinsulin (30 pmol/L), and BOHB levels (6500μmol/L). MR and multiphase CT () showed a solid, hyperenhancing 2.5cm pancreatic tail mass with slow washout. 111In-pentetreotide (Octreoscan) study () demonstrated absence of radiotracer uptake ruling out a splenule. CT guided fine needle biopsy of the mass confirmed neuroendocrine etiology. Since Octreoscan sensitivity is not high, hepatic vein blood sampling after intra-arterial calcium stimulation was further performed and showed robust increase of insulin (9.4 to 17.8mIU/L) and proinsulin (7pmol/L to 20pmol/L) and high c-peptide levels at the distal splenic artery, consistent with insulinoma of the tail of the pancreas. Surgical excision of the mass resulted in complete resolution of symptoms up to 3 years postop. Histologic examination confirmed a well differentiated neuroendocrine tumor with immunostainings positive for chromogranin and synaptophysin and a KI index of <2%.
pmc-6387709-1	The patient is an 18-year-old boy not known to have any medical illness previously, who was referred to the outpatient department from another hospital after 3 months history of seizures. Seizures started with blurring of vision and proceed to right sided head deviation and tonic posturing of the right upper limp which progress to generalized tonic-clonic seizures. The episodes are followed by loss of consciousness and postictal suboccipital and frontal tension headache. There was no history of fever, loss of weight, trauma, or any sensory/motor neurodificit. Family history was unremarkable, with negative past surgical history. All general and local physical examinations were done and all were within normal range. There were no physical findings or family history in favour of neurofibromatosis. Brain MRI with contrast was done and showed right parieto-occipital cortical and subcortical mass lesion measuring about 1.5 x 1.5 cm that has a low signal intensity on T1 and intermediate signal intensity on T2 and FLAIR with intense enhancement postgadolinium administration mainly peripherally with few small susceptibility artefact on T2 associated with significant vasogenic oedema and mass effect on the adjacent sulci (). The radiological impression with the above description was most likely representing granulomatous infection (TB) or metastasis. Although a preoperative diagnosis could not be clearly established, the tumor was surgically removed through a right occipital craniotomy. The dura was incised and small area of discoloration was noted. Cortical dissection was done, with multiple pieces for frozen section, which was diagnosed later as suggestive of schwannoma, differential diagnosis meningioma. The tumor was encountered 2mm in subcortical area, which was firm, fibrous in content, yellowish in colour, and resembling meningioma. Postoperatively, the patient did not have any new neurological deficit, and he was discharged 1 day postoperatively in stable condition to be seen and followed up in the clinic after 2 months. He was kept on phenytoin 100 mg orally three times a day and Paracetamol 650 mg tablets 4 hourly PRN. Microscopic examination of the tissue showed areas of nuclear palisading of bland looking spindle cells with dens cellular area alternating with loosely textured myxoid area, consistent with Antoni type A and Antoni Type B, respectively (). Immunohistochemical study was diffusely positive for S100 protein and negative for EMA, confirming the diagnosis of schwannoma (WHO grade1).
pmc-6387716-1	A 70-year-old female with a history of three years of right shoulder pain presented with limitation in both active and passive ranges of motion. Upon physical examination, Jobe's test and Hawkins test both showed positive results, indicating dysfunction of the rotator cuff and impingement in the shoulder joint, respectively. Plain radiograph showed joint space narrowing with bone deformity, sclerotic change, and subchondral cyst formation in the glenohumeral joint; the patient was thus diagnosed as advanced osteoarthritis. MRI evaluation revealed an approximately 1 cm tear in the rotator cuff, specifically in the supraspinatus muscle on its articular side, as well as tendinosis and subtle muscular signal change in distal subscapularis (). The patient underwent an anatomic shoulder arthroplasty considering the functional deltoid muscle. The deltopectoral approach was used for the surgery. Upon blunt dissection to the subdeltoid and subacromial spaces, a superior portion of the pectoralis major muscle was released. The subscapularis tendon was released from its insertion site followed by capsulotomy. A distinct muscular structure was found at the anterior-inferior aspect of the glenoid rim (), which was not determined as part of the glenoid labrum. This muscle was carefully tagged and dissected near its origin site to allow glenoid reaming. A routine anatomic total shoulder arthroplasty was carried out afterwards. The muscle was repaired along with the SM. No major complications were found. The patient was discharged at seven days postoperation.
pmc-6387721-1	A 33-year-old woman presented to the emergency services for pain in the lower abdomen and anorectal pain. A detailed medical history of the patient revealed that her partner had inserted a foreign object into her rectum to achieve sexual satisfaction. The patient stated that she had not seen the foreign object and she did not know the nature of the material. On physical examination, the abdomen was relaxed but at the palpation a hard object could be felt. Complete blood cell count (CBC) and biochemical parameters were within a normal range. On digital rectal examination, the base of the object was palpated as a solid object 8-9 cm proximal to the anus. Standing abdominal radiographs of the patient were obtained in an emergency department for differential diagnosis and showed a bottle in the rectum without any evidence of free air or air-fluid levels (). To obtain accurate information regarding the nature and location of the foreign object, the relationships with surrounding tissues, and potential complications, a CT was done (). A 17 cm foreign body is viewed at the rectosigmoid level. The thickened appearance and hyperemia of the rectal walls indicates an associated proctitis. The patient was transferred to an operating room, the anal canal was dilated under general anesthesia, and the object was removed manually by pressing on the abdomen. Digital transanal extraction was successful after 45 minutes, when a total relaxation has been achieved and by applying bimanual continuous pressure on the anterior abdominal wall. The extracted object consisted of a lubricant gel tube (). The postoperative period was uneventful.
pmc-6387725-1	The proband is a 39-year-old South Asian female of Indian origin who was diagnosed with systemic amyloidosis of unknown type when she was 16 years of age. At the time of diagnosis, she was pregnant and was experiencing gastrointestinal symptoms of abdominal bloating, dyspepsia, heartburn, and nausea. These symptoms persisted postpartum, and the patient underwent an upper endoscopy with biopsy, which was consistent with the presence of amyloid material; however, the type could not be determined. Thereafter, the patient continued to live a fairly normal life and did not seek any further medical attention until her daughter who when turned 16 started experiencing similar symptoms and underwent an upper endoscopy with biopsy results consistent with the presence of amyloid. At that time, the family sought medical attention at our institute. The proband reported that, in spite of an overall normal life, she had continued to experience dyspeptic symptoms that worsened with stress. She also reported around 12–15 episodes of hematemesis since her initial diagnosis. Additional symptoms on close questioning included easy bruisability, periorbital purpura, and ecchymosis associated with activities such as retching and vomiting. An upper endoscopy was performed at the Mayo Clinic. No morphological abnormality was seen on the endoscopy; however, Congo red stain demonstrated the presence of amyloid material in the gastroesophageal junction, stomach, and duodenum. Serum and urine protein electrophoresis were normal. Proteomic assessment with laser capture mass spectrometry (LCMS) evaluation of the congophilic material detected an amino acid sequence abnormality in the lysozyme protein (I56T). Peripheral blood genotyping confirmed I56T mutation (DNA change c.221T > C) in exon 2 of the lysozyme gene, which replacing isoleucine with threonine at position 56. I56T mutation per human genome variation society (HGVS) nomenclature is now known as I74T. Patient's renal and hepatic functions were normal, and she did not have any adenopathy. Besides iron deficiency and mildly delayed gastric emptying, no other abnormality was noted. The patient continues with yearly follow-up in our amyloidosis clinic with periodic exacerbations of dyspeptic symptoms and a few episodes of small-volume hematemesis, which have responded to high-dose acid suppressive treatment.
pmc-6387729-1	A 21-year-old Caucasian man was admitted to the University Hospital of Patras, Western Greece, with fatigue, fever up to 39°C, and retrosternal pain. He denied anorexia, night sweats, and generalized malaise. No significant past medical history was reported. There were no risk factors for HIV infection, no recent travel outside Greece, and no exposure to animals. The patient denied smoking and drinking, and also no allergies were noted. On physical examination, the temperature was 39.0°C, the heart rate was 90°bpm with sinus rhythm, and the blood pressure was 120/80 mmHg. The patient was respiratory stable (respiratory rate 16/min and oxygen saturation 98% on room air). No cervical or supraclavicular lymphadenopathy was identified. There were no murmurs, rubs, or gallops, and the lungs were clear on auscultation and percussion. The abdomen was nondistended, with normal active bowel sounds and mildly tender in the midepigastrium but without rebound or guarding. No liver or spleen enlargement was noted. No abnormalities like clubbing, cyanosis, or edema were found on all extremities. The rest of the examination was unremarkable. Electocardiography (ECG) revealed a sinus rhythm with ST elevation (ST 2 mm in I, II, aVL, and V4–V6) (). Furthermore, laboratory tests showed a low platelet count 134.000 (normal range 150.000–400.000 Κ/μl), raised aspartate aminotransferase (193 U/L, upper normal limit (UNL) 40 U/L) and alaninoaminotranferase (42 U/L 40 U/L), high CPK levels (2166 mg/dl, upper normal limit 190 mg/dl) with CPK-ΜΒ lower than 10% of total CPK (112 mg/dl), troponine (ΤnI) 48.51 ng/ml, and CRP 4.60 mg/dl. The hemogram was normal (). Chest X-ray image did not reveal any abnormalities. Blood and urine cultures were taken on admission. The transthoracic echocardiography Doppler showed wall motion abnormalities and absence of pericardial effusion. Accordingly, a cardiac MRI using delayed enhancement was performed (Figures and ) revealing recent myocardial damage with edema and fibrosis in the middle and upper left and right lower wall and increased left ventricular dimensions with normal systolic function. In addition, cardiac MRI revealed overriding of the right ventricle with normal systolic function Serology for Influenza A and B, parvovirus B19, EBV, and CMV, ECHO virus, Coxsackie virus, HSV, VSV, and adenovirus, Coxiella burnetii, Chlamydia, Leptospira spp., and Mycoplasma pneumoniae were negative. On day 3 of hospitalization, Brucella melitensis was isolated from two consecutive blood cultures. The Brucella serum agglutination test (SAT) was positive >1/1280, so a diagnosis of Brucella-related myocarditis was made. Treatment with oral rifampicin (900 mg once daily) and doxycycline (100 mg twice daily) along with intravenous gentamycin (320 mg once daily) was immediately commenced. Gentamycin was administered for ten days. The patient recalled that he had consumed unpasteurized goat cheese a month ago. After five days of treatment, the patient was clinically improved, asymptomatic, and fever was regressed. No signs of cardiac arrythmias or other ECG abnormalities on serial ECGs, during hospitalization, were noted. On discharge day, all laboratory tests were normal (). Patient had a total antibiotic course with Doxycycline and rifampicin for 6 months.
pmc-6387739-1	A 3-month-old Hindu baby boy presented with a congenital neck swelling on the right side of his neck. There was no history of birth trauma or breech delivery. Initially a small midline swelling, it progressively increased in size with age. It was soft and compressible with an overlying bluish hue at places. With a working diagnosis of a low flow lymphovascular malformation at another hospital, intralesional bleomycin was injected once after which the swelling became a little firm without any change in its size. One month after the bleomycin injection, it was a 5.5 × 7.5 cm firm, non-tender, well-defined swelling in the midline and extending into the right supraclavicular region (Fig. ). There was no retrosternal extension and no movement with deglutition or cervical lymphadenopathy. Imaging suggested a diagnosis of lympho-venous malformation (Fig. ). However, there was a remote suspicion of malignancy as there were interspersed solid areas. Serum alpha-fetoprotein levels were in the normal range for age. On exploration, a friable, solid mass with a pseudocapsule was encountered without any cystic component. It encased the sternal head of right sternocleidomastoid, part of which had to be sacrificed. A frozen section sent during excision was suggestive of malignancy. Complete gross resection of the lesion was done. There were no obviously enlarged neck nodes. Histopathology revealed a tumor comprising spindle-shaped fibroblast-like cells along with large areas of hemorrhage (Fig. ). Tumor cells were arranged in fascicles and at places in a herringbone pattern. There was brisk mitotic activity and moderate degree of anisonucleosis. Cells were immunopositive for desmin but negative for myogenin, smooth muscle actin (SMA), pancytokeratin, epithelial membrane antigen (EMA), MIC-2, and CD-34. Sternocleidomastoid muscle was free of tumor. The diagnosis of CIFS was favored over spindle cell rhabdomyosarcoma in view of absence of myogenin positivity. A metastatic workup was negative. No chemoradiotherapy was initiated and the child was kept under close follow-up. A follow-up contrast-enhanced computed tomography scan (CECT) of his neck and chest showed no residue or recurrence at 3 and 6 months. He is thriving well and was disease free at 2-year follow-up.
pmc-6388320-1	An 8-month-old baby boy was presented to our clinic with a one month history of right elbow mass. The patient's mother claimed that the child is moving his right upper extremity actively without any limitation. She also reported gradual increase in the mass size in the last month. The patient is previously healthy without any past medical or surgical history. The patient is a product of full-term pregnancy with no perinatal complications. His developmental history was uneventful with no family history of malignancies. Physical examination revealed a 3 × 2 × 4 cm mobile soft nontender mass extending from the right proximal ulnar aspect volar surface crossing the elbow crease proximally with no signs of erythema (). The full elbow active extension with mild restriction of full flexion is around 15 degrees. Plain radiograph of the right elbow showed a lobular soft tissue swelling () with a normal blood profile (complete blood count, ESR, CRP). The MRI of the right elbow revealed a 3.3 × 2 × 4.5 cm (AP, transverse, and CC dimension) lobular juxta articular subcutaneous soft tissue lesion along the medial aspect of the elbow. The lesion appeared multiseptated with a predominantly high T2 signal intensity and contains a 1.8 × 1.8 × 1.5 cm area with low T2 and high T1 signal intensity and no perilesional edema or joint effusion (Figures and ). The overall findings were in favor of an endolymphatic malformation. Decision was taken for radical excision. Radical excision was performed under tourniquet control with dissection of the mass from the ulnar, the median nerves, and the antebrachial muscles (). Pathology specimen of the tumor showed a multiloculated lymphangioma with no evidence of malignancy (). The lesion showed vascular spaces with thick vascular walls incorporating adipose tissue and nerve fascicles. The vascular spaces were lined by regular endothelial cells. Surrounding synovial fluid cytology was negative for malignancy with rare regular cell present. The patient was discharged day 2 post-op in a good condition. Follow-up at 2 weeks, 1 month, and 6 months post-op was satisfactory with elbow full range of motion and normal median and ulnar nerve function.
pmc-6388324-1	The patient was a 49-year-old Nepalese man who was an HIV-1-positive injecting drug user coinfected with hepatitis B and C. He was informed and written consent was obtained for collection of blood samples for follow-up investigation. All the necessary tests and analysis were performed at the National Public Health Laboratory (NPHL), Kathmandu, Nepal. The blood sample was collected in a plain and K2 EDTA tube (BD Vacutainer). The rapid diagnostic testing for HIV-1/2, HBV, and HCV was performed using rapid immunochromatography, while syphilis testing was done using the flocculation method for VDRL (RPR). The reactive and nonreactive results were further confirmed by enzyme-linked immunosorbent assay for HBsAg, anti-HCV, and anti-HIV 1/2 (ELISA Human, Germany) and electrochemiluminescence immunoassay for HBeAg, HBsAg, anti-HBs, anti-HBe, anti-HBc, anti-HCV, and HIV Combi PT (ECLIA, cobas Roche Inc., Germany). The ECLIA was performed using cobas e 411 analyzer (Roche Inc., Germany). The whole blood collected in EDTA was used for CD4+ count using a BD fluorescent-activated cell sorter system (BD Biosciences, San Jose, CA, USA). The viral nucleic acid (DNA/RNA) was extracted using the QIAamp® DSP Virus kit (Qiagen, Germany). HBV DNA and HCV RNA were quantified by Corbett Rotor-Gene 6000 Real-Time PCR. The Artus HBV/HCV RG PCR kit (Qiagen, Germany) allows for a viral load detection limit of 10–100,000,000 IU/ml for HBV-DNA and 65–1,000,000 IU/ml for HCV-RNA with 97% specificity. HIV-1 was amplified and quantified by a Cobas® TaqMan® 48 analyzer. The COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 Test, v2.0 (Roche Molecular Systems, Inc., USA), has an assay of linearity from 20 to 10,000,000 copies/ml with 100% specificity. The patient was tested positive for HIV-1/2 infection with hepatitis B and C coinfections first time at a tertiary care hospital of Nepal on 14 August 2017. The initial finding at the time of HIV-1/2 confirmation showed decreased CD4+ nadir and SGOT. The client was informed that he was HIV-1/2 positive, and appropriate counseling was provided regarding the HIV, risk factor, transmission to family, social issues, and availability of ART. He was prescribed a fixed-dose combination of tenofovir disoproxil fumarate (TDF), lamivudine (3TC), and efavirenz (EFV) as the preferred option to initiate ART according to the National HIV Testing and Treatment Guidelines 2017, Nepal. It also covers for HBV infection. However, the patient was not in HCV treatment. He also mentioned that his spouse was positive for HIV-1/2. After ten months of ART initiation, he visited for follow-up on 5 June 2018. The follow-up investigation includes a routine laboratory test on hematological parameters, biochemical parameters, and viral loads. The HCV was tested negative using rapid chromatography but confirmed positive using ELISA and ECLIA. However, the improved CD4+ count was observed after ART. Final testing of viral loads for HIV-1, HBV, and HCV was performed for monitoring of ART. The schematic flowchart of the case presentation is shown in , and laboratory investigation of patient test reports is presented in .
pmc-6388332-1	A 56-year-old Japanese man was referred from a dental clinic for further examination of a radiolucent finding on the left side of his mandible in January 2010. The patient reported having no symptoms in his mouth including the left mandible area. His medical and dental history was noncontributory. An extraoral examination upon initial presentation revealed unremarkable findings and no complaints of paresthesia. An intraoral examination also confirmed the absence of redness and tender swelling of the left mandibular mucosa (). Panoramic radiography revealed an extensive multilocular radiolucent area with imprecise borders and a “soap bubble appearance” (). Computed tomography showed an approximately 39 × 19 × 11 mm tumor that extended to the roots of four teeth (#33 - 36; Figures and ). We considered that the odontogenic tumor was benign and an incisional biopsy was performed under local anesthesia. The histopathological findings revealed loosely arranged spindle-shaped cells in a myxoid fibrous stroma, indicating a clinical diagnosis of an odontogenic tumor. Segmental resection of the mandible was planned. The patient was given repeated and careful explanations about the high likelihood of recurrence, but he insisted upon a more conservative approach as he desired functional and cosmetic preservation. Conservative surgery then proceeded under general anesthesia after endodontic treatment of #33 – 36 was completed. The surgery consisted of extracting the second premolar from the left mandible, followed by total enucleation and vigorous curettage of the bone (). The surgical specimen () revealed apparently benign, spindled-shaped cells in a loose and abundant mucoid stroma (Figures and ). These findings confirmed the diagnosis of odontogenic myxoma. The immediate postoperative period and wound healing were uneventful. The patient underwent monthly clinical examinations for the first year thereafter, then every two months during the second year. Panoramic X-rays were obtained every three months for the first two years. Annual follow-up for eight years included panoramic X-rays and CT imaging (Figures and , respectively), which showed no clinical or radiological signs of recurrence.
pmc-6388339-1	A 49-year-old Caucasian male was evaluated at the Department of Adult Psychiatry Intensive Outpatient (IOP) Treatment Program for initial intake after having been referred from the Department of Neurology Outpatient Clinic. He had complaints of depressed mood, lack of enjoyment of pleasurable activities, sleep disturbances, poor concentration, and occasional passive suicidal thoughts. These symptoms were in association with ongoing progression of symptoms related to his diagnosis of SCA1. His neurologic symptoms included coordination problems and ataxia initially at diagnosis, but in recent years speech impairment, swallowing difficulties, some spasticity, and eventually muscle atrophy were presented. He had to utilize a motorized wheelchair as a result of his progressive disability. His current house was not fully wheelchair accessible. He lived alone but had siblings who visited at least several times per week. He also seemed to lack insight into the relationship between his thoughts, feelings, and physical limitations. At the psychiatric evaluation, he expressed that his self-esteem was strongly affected by his limited physical mobility due to his SCA1, and he seemed extremely unhappy. He reported passive death wishes at least once a week, usually without a suicidal plan or intent. Laboratory evaluations including hemogram, liver function tests, total protein, vitamin B12, folic acid, T3, T4, and TSH were within normal limits. Baseline psychiatric evaluation with the Beck Depression Inventory (BDI-II) [] revealed scores of 23 (moderate depression). According to clinical evaluation as well as DSM-V [] criteria, the patient was diagnosed with major depressive disorder and he was started on sertraline 50 milligrams (mg) by mouth per day. He had never taken medications for depression before. Group cognitive behavioral therapy focusing on negative cognitions as well as aspects of dialectical behavioral therapy were initiated as part of the IOP protocol []. These group sessions occurred three times a week for several hours a session totaling approximately 12 hours per week. Individual cognitive behavioral therapy with a psychologist also occurred weekly for the first several weeks of the IOP program. He also met with a psychiatrist weekly, then every two weeks, and finally monthly for medication management. His sertraline was increased over this time period to 100 mg per day. He reported compliance with medications and reported no side effects. He also participated in 3 family sessions whereby his family members were also engaged in psychoeducation and therapy. Partial response to treatment was observed at the 12th week with reduction of BDI-II [] score to 12 (mild mood disturbance). He participated in the IOP program for approximately 6 months in total, becoming increasingly more engaged, and eventually reported a subjective significant reduction in depressed mood, anhedonia, and suicidal thoughts. His sleep and concentration also improved. He reported improved insight into the mind-body connection between his physical and emotional conditions. He acquired new coping skills to limit counterproductive behaviors and irrational emotional responses to his occasional negative thoughts. With help of IOP staff and social workers, he found an assisted living accepting of his limited ambulation, moving to a better housing situation. He then was eventually scheduled for medication management and monitoring follow-up appointments in the Department of Adult Psychiatry Outpatient clinic once discharged from the IOP treatment program.
pmc-6388341-1	A 66-year-old female patient with a history of bilateral lower limb lymphedema reported the aggravation of the condition over the years, reaching stage III (elephantiasis). The patient was sent to the Godoy Clinic and reported having undergone several treatments throughout her life as well as several episodes of erysipelas. She did not marry due to the lymphedema and complained of the frequent occurrence of strangers staring at her leg, which upset her. The physical examination confirmed elephantiasis. The circumference of the left lower limb was 106 cm. Her body weight was 106 kilograms, height was 160 cm, and the body mass index (BMI) was 41.6 kg/m2 (). The patient was submitted to intensive treatment for three weeks, which led to a 21 kg reduction in weight and 66 cm reduction in leg circumference (). Intensive treatment with the Godoy Method consisted of eight hours per day of mechanical lymphatic drainage, 15 minutes of simultaneous cervical lymphatic therapy, and hand-crafted compression stockings made from grosgrain fabric. Mechanical lymphatic therapy consisted of an electromechanical device that performs plantar flexion and extension. After three weeks of intensive therapy, the patient continued treatment at home using the compression stockings. At the follow-up evaluation, the patient was submitted to electrical bioimpedance analysis as well as circumference measurements and volumetry. The bioimpedance analysis revealed a pattern of normality, with the reduction in lymphedema. Ten years after treatment, the patient has maintained the results with the compression stockings. In occupational therapy throughout this period, the patient has been encouraged to perform activities that she has always wanted to do to improve her wellbeing. She took up belly dancing, followed by tap dancing. She reports that these activities changed her life and she is very happy for being able to realize her dream of dancing, which is an activity that she began at the age of 76 years. The study was approving Ethical Committee of Medicine School of Sao Jose do Rio Preto# 2.929.115.
pmc-6388474-1	The patient was a 50-year-old female who underwent surgery in 2004 for mucinous breast carcinoma of the right breast [T2N1M0 (IIb)], and received postoperative CMF (cyclophosphamide+methotrexate+fluorouracil) chemotherapy, radiotherapy with 50Gy and endocrinotherapy with tamoxifen for 5 years. Unfortunately, she did not receive any follow-up examination after completion of the treatment. In 2015, she found that the right local surface of the scalp had become irregular and was increasing in size without pain or numbness. More than 1 year later, the patient experienced a slight headache which was relieved with antipyretic analgesics. Then edema of the frontal scalp and bilateral upper eyelid followed, particularly on the right side. She denied any past trauma history. The physical examination revealed the following: edema of the bilateral frontal scalp and upper eyelid, the right frontal, temporal, and dorsal scalp were slightly lumpy with normal scalp color, and the lumps were immobile and solid but without tenderness. The right thoracic wall was modified due to the prior radical mastectomy for the treatment of breast cancer and the right upper limb was free of edema. Neurological examination revealed no abnormalities other than the slight headache. No abnormalies were found in the remaining examinations. Laboratory examination: The results of routine blood and urine examinations were normal, as were those of the biochemistry examination. Computed tomography (CT) revealed that the bilateral frontal bone, right temporal bone and right parietal bone were diffusely and osteolytically destroyed with soft tissue lesions. (Fig. ). No metastatic lesions were observed on the CT images of the chest, abdomen, and pelvis. The magnetic resonance imaging (MRI) results revealed that the bilateral frontal bone, right temporal bone, and right parietal bone were thickened with nodules. The lesions were tent-like on coronal and sagittal planes (Fig. e, f). The lesions exhibited a slight hypointensity on T1-weighted imaging (T1WI) (Fig. a), and isointensity on T1-weighted imaging (T2WI) (Fig. b) and T2-fluid-attenuated inversion recovery (FLAIR) (Fig. c) images, and were significantly enhanced (Fig. d, e, f) after enhancement. The meninges of the right frontal, temporal, and parietal areas were also diffusely thickened with nodules. The nodules compressed the right temporal lobe slightly and led to edema of the parenchyma (Fig. a, b, c), which was not enhanced (Fig. d, e). There was slight compression of the adjacent brain parenc hyma and ventricle. The brain midline structure shifted to the left by approximately 0.5 cm, and the size of the meningeal nodular lesions was approximately 2.8 × 1.3 × 2.8 cm. The tumor marker levels were: carcinoembryonic antigen (CEA) 11.52 ng/ml, cancer antigen 15–3(CA15–3) 77.39 U/m l. The results combined with the medical history, led us to suspect the presence of a metastatic tumor with invasion of the right temporal and occipital meninges. Systemic bone imaging revealed abnormal bone metabolism in the skull (Fig. ). To evaluate the nature of the lesion, open biopsy was performed. The pathological diagnosis of the biopsy was hemangioma of the skull (Fig. ). The corrected diagnosis was cranial cavernous hemangioma. Based on the CT and MRI findings, the headache and upper eyelid edema of the patient were considered to be caused by the local invasion of the skull lesions. The patient received a normal three-dimensional conformal radiotherapy with a dose of 60Gy/30F (the lesions nearby bilateral upper orbital bone was 50Gy/30F). The target volume was described as: according to CT and MRI images to delineate the target, gross tumor volume (GTV) comprised the skull, meningeal and Right temporal lobe lesions, GTV was enlarged 3 mm circumferentialy to form the planning target volume (PTV). Irradiation was performed using 6 MV X-rays. At the end of the radiotherapy, the size of the lump at biopsy site (the primary right frontal, temporal, and top scalp) was slightly reduced on physical examination, but the head CT showed no significantly change compared to pre-radiotherapy CT images (Fig. ). The symptoms of discomfort in the head and eye swelling were relieved. We concluded that the blood vessels of lesions in skull may be blocked. The patient reported no symptoms during the 1-year telephonic follow-up. Unfortunately, the CT scan during 1-year follow-up was performed at an outside institution and was not available for inclusion in this report.
pmc-6388486-1	A 79-year-old Caucasian woman came to our attention complaining of dull, diffuse abdominal pain and high body temperature (38 °C). She had high blood pressure and type 2 diabetes, for which she was receiving oral ramipril 5 mg twice daily and metformin 500 mg three times daily, respectively. She was a housewife. Her parents had died of cardiovascular diseases in advanced age. She denied tobacco or illicit drug use and rarely drank a glass of wine. The patient reported a history of bile stones in her gallbladder and her common bile duct. She stated that she had undergone endoscopic bile stone extraction (endoscopic retrograde cholangiopancreatography with papillotomy) and laparoscopic cholecystectomy 3 years before. Cholecystectomy was completed with choledochotomy in order to extract further bile stones and for the positioning of a Kehr’s T tube. Postoperatively, a single daily dose of prulifloxacin 600 mg was taken for 5 days. Two months later, the Kehr’s T tube was removed, and a new antibiotic therapy (always with single oral intake of prulifloxacin 600 mg for 5 days) was established. At reevaluation with abdominal computed tomography (CT), no bile leakage or biliary obstruction was detected. Six months later, the patient returned to the hospital with a 4-day history of high body temperature (> 38 °C), right upper abdominal quadrant dull pain, and dyspnea. Her bowel sounds were normal; at palpation, abdomen was globally painful, with a mild tenderness at the right upper quadrant. Chest examination showed bilateral lower diaphragmatic excursion, decreased vocal fremitus, and attenuated sounds at pulmonary bases. The patient was oriented, and her language was fluent with good comprehension. Her neurological examination result was normal: Her pupils were equal, round, and reactive to light; visual fields were intact to confrontation; fundi were normal; ocular movements were intact; muscle bulk and tone were normal; sensation was intact to light touch, pinprick, vibration, and proprioception throughout; Romberg test result was negative; reflexes were normal throughout, and plantar response was flexor bilaterally; no dysmetria was observed on finger-nose-finger or heel-knee-shin; normal rapid alternating movements; and fast finger tapping with normal amplitude and speed. The patient’s blood pressure was 110/70 mmHg, and her heart rate was 97 beats per minute. Blood laboratory parameters showed severe leukocytosis (19,000 white blood cells/mm3). The patient was promptly started on broad-spectrum antibiotic therapy with endogenous piperacillin-tazobactam 4.5 mg twice daily and endovenous levofloxacin 500 mg once daily. An x-ray showed a homogeneous opacification of the right pulmonary lower zone and a slight elevation of the homolateral hemidiaphragm; the left costophrenic angle was obliterated with a meniscus. The findings were suggestive of a bilateral pleural effusion most relevant in the right side. Abdominal ultrasonography (US) showed multiple hypoechoic, loculated fluid collections within the liver parenchyma consistent with HA and confirmed pleural effusion. The subsequent contrast-enhanced chest and abdominal CT scan confirmed the presence of the HA (a 13-cm hypodense circular mass at hepatic segments VI, VII, and VIII) and marked the presence of a mild bilateral pleural effusion. Then, the patient underwent CT-guided drainage of the HA; at the same time, a 7-F multipurpose drainage catheter was positioned. In this case, the collected fluid was not examined. The chest and abdominal CT scanning performed 5 days later showed a severe right pleural effusion, whereas the left one remained superimposable to that shown 5 days before; the multipurpose drainage catheter was in the right position (close to the hepatic bare area), surrounded by plenty of retroperitoneal fluid. The patient was discharged with oral antibiotics (levofloxacin 500 mg once daily and ceftriaxone 400 mg once daily for 15 days), and a control contrast-enhanced CT scan was scheduled for 1 month later. In this case, the examination showed a mild right pleural effusion and a well-circumscribed 9.5 × 4.5 × 9-cm fluid collection in the back of the thoracic cavity, pushing against the lower lobe of the right lung; abdominal slices showed a small 15-mm formation, laying on the posterior surface of the liver and imprinting the VIth segment, resulting from the drained abscess. The subsequent control chest and abdominal CT scan, obtained 4 months later at the same hospital, showed an improved picture with a slight residual right pleural effusion and no signs of thoracic abscess or HA. At the time of admission to our hospital 3 years after the last event, the patient complained of high body temperature and abdominal pain. Her body temperature was 38 °C, and she felt very weak. Her blood pressure was 100/60 mmHg, and her heart rate was 110 beats per minute. Her abdomen was slightly globose, but her bowel movements were present. She complained of an intense pain in her hypogastrium when a deep palpation was applied. Chest and neurological examination results were normal. Complete blood count showed only a mild leukocytosis (14,700 white blood cells/mm3), and her C-reactive protein level was 6.9 mg/dl. A chest x-ray was taken, but it was not clinically relevant. Abdominal US revealed a remarkable fluid collection in the patient’s pelvis. Upon admission, a single daily oral dose of Levofloxacin 500 mg + intravenous Ceftriaxone 2 g once daily were prescribed. A progressive improvement of clinical condition was observed, also confirmed by laboratory tests (see Table ). At day 19 after admission, a contrast-enhanced chest and abdomen CT scan was repeated; interestingly, the CT scan showed presence of a large, irregular, loculated fluid-density formation, of about 18 cm in diameter, with rim enhancement and internal septation. The collection was located posteriorly to the right kidney, displacing it anteriorly. The VIth and VIIth liver segments were compressed, and the abscess extended to the retroperitoneal space; furthermore, it spread to the right lateral wall of the abdomen, extending across the muscular wall to the subcutaneous layer. The fluid collection also involved the right pleural cavity, forming an empyema of about 14 cm in major diameter (Fig. ). CT-guided aspiration of the fluid collection was performed. The needle was inserted into the right lumbar region, and an 8-French multipurpose drainage catheter was positioned. Immediately, 450 ml of a grayish smelly fluid came out. Eight milliliters of the fluid were collected in an anaerobic vial (ambient temperature) and quickly sent to the Microbiology Laboratory of Palermo University Hospital. The fluid was analyzed using Grocott and periodic acid-Schiff stains for cytology, which demonstrated the presence of granulocytes, histiocytes, and bacterial debris (suspicious for Actinomyces). The aspirate material was also submitted to Gram staining and culture (aerobic, anaerobic, Mycobacterium tuberculosis, and fungi), but the results did not show any kind of bacterial or fungal growth. Culture media and techniques were carried out according to international standards for the research of the specific microorganisms. A few days later, a multipurpose drainage catheter was positioned. A CT scan showed a timely reduction of the abdominal and thoracic collections. A blood culture was not obtained. The patient was discharged 70 days after admission in good clinical condition. Before discharge, whole-body CT was performed, which showed a complete reabsorption of fluid collections. Of note, during her hospital stay, the patient’s indirect bilirubin level was raised. Owing to Coombs test positivity, this was likely caused by an immunologic response to long-term antibiotic therapy. Fourteen months later, the patient came back to our care after 1 month of a dull pain in her right lumbar region. A few days before admission, she complained of high body temperature (> 38.5 °C) and a huge swelling with reddened skin in the same area hit by pain. At admission, her blood pressure and heart rate were normal (120/80 mmHg and 75 beats per minute, respectively), but her body temperature was high (38 °C). The result of her abdominal examination was globally normal. Laboratory blood tests did not show any relevant alteration, apart from mild leukocytosis (10,000 white blood cells/mm3). The patient was promptly started on broad-spectrum antibiotic therapy with endovenous piperacillin-tazobactam 4.5 mg twice daily and endovenous levofloxacin 500 mg once daily. A chest/abdominal CT scan showed a new retroperitoneal fluid collection extending beyond muscular layers toward the skin of the lumbar region. A few days later, a 14-French drainage catheter was positioned, and the patient was discharged in good clinical condition. One week thereafter, the abscess was no longer present. Three months after the last follow-up, the patient came back to our attention with an evident swelling of her right lumbar region. Her skin was slightly reddish but not dystrophic. She did not report any symptom related to the neoformation. Her blood pressure, heart rate, and body temperature were normal (120/80 mmHg, 75 beats per minute, and 36.5 °C, respectively). Her blood test did not show particular alterations. The right lumbar region showed reddened skin with a 10 × 10-cm swelling. Upon palpation, it was globular in shape and soft in consistency with smooth surface and well-defined borders. It was expansive on coughing and straining. No pulsations were felt over the swelling. Suspecting a new relapse of the disease, we obtained a CT scan, and a right inferior lumbar hernia (Petit hernia) containing adipose tissue and the right kidney was detected (Fig. ). To better understand the case, a visual timeline was provided. A surgical intervention was recommended to the patient, but, owing to her poor general health, she refused any invasive approach. To date, the patient is alive and continues her life with her lumbar hernia. No further abscesses have been detected. The timeline in Fig. summarizes the sequence of events during the patient’s clinical course.
pmc-6388674-1	A previously healthy, Caucasian, 18-year-old man presented at our Department of Emergency Medicine for watery diarrhoea, high-grade fever, and severe malaise. Stool samples performed by the family physician had been negative, including testing for Salmonella species (spp.). Five days after returning from travelling to various countries, e.g. India and Nepal, he developed fever, chills, cough, sore throat, and headaches, which lasted for 3 days before diarrhoea started. The total duration of the disease on admission was 7 days. day 1: Germany day 2–4: Kingdom of Bahrain day 4–8: United Arab Emirates (Dubai: day 4–6; Abu Dhabi: day 6–8) day 8–11: Kathmandu, Nepal day 11–13: Delhi, India day 13–16: Kuala Lumpur, Malaysia day 16–18: Singapore day 19–23: Melbourne, Australia day 24–26: Taipei, Taiwan day 26–28: Manila, Philippines day 28–29: Kuwait City, Kuwait During his travels, he experienced gastroenteritis while he was in Delhi (oral antibiotic therapy and electrolyte solution resulted in cure after 3 days), and multiple mosquito bites in malaria-endemic countries. He denied tick bites and animal contact of all kinds. Although he had received pre-travel medical advice, he did not respect alimentary precautions (he preferred vegetables and salad in local restaurants), and had refused malaria prophylaxis due to fear of side effects. The patient did not receive any vaccination against cholera or typhoid fever. Apart from signs of exsiccosis, a thorough physical examination was unremarkable. The patient was fully conscious, had a relative bradycardia (95/min), hypotension (95/60 mmHg), high-grade fever (39°C), and normal oxygen saturation. Electrocardiogram was normal and abdominal ultrasound was consistent with diagnosis of gastroenteritis. A differential blood count demonstrated a normal white blood count, aneosinophilia and discrete thrombocytopenia (126/µl, normal: 140–200/µl). Laboratory examination revealed an elevated CRP level (93 mg/dl; normal: <5 mg/dl) and slightly elevated ALT (48 U/l, normal: <40 U/l), AST (59 U/l, normal: <41 U/l) and LDH (461 U/l, normal: <250 U/l). Creatinine levels, blood gas and urine analysis were normal. Malaria was ruled out using thick smears and rapid testing. Blood, urine, and stool cultures were performed. The latter two showed no growth. Due to suspected typhoid fever, we started intravenous ceftriaxone (2 g once daily), fluid supplementation (2.500 ml per day), and oral antipyretics (750 mg metamizole four times daily). Liver enzymes increased to ALT 97 U/l and AST 83 U/l on day 8 after disease onset; to ALT 196 U/l and AST 165 U/l on day 9 after disease onset. Diarrhoea subsided to 15–20 times per day; fever subsided as well. On day 11 after disease onset, blood cultures revealed Gram-negative bacteria. By the time, the patient’s condition had not improved. We suspected a Gram-negative sepsis and changed the antibiotic regime to intravenous meropenem, 1 g three times per day. One day later, Salmonella enterica Serovar Typhi was identified (susceptibility testing: Table 2 ), and the therapy was continued with meropenem. Liver enzymes peaked on day 12 after the onset of initial symptoms: LDH 756 U/l, ALT 544 U/l, AST 263 U/l, alkaline phosphatase (AP) 168 U/l (normal: 55–149 U/l), and Gamma-GT 196 U/l (normal: <60 U/l). Bilirubin remained normal; abdominal ultrasound displayed mild hepato- and splenomegaly. We ruled out hepatitis A/B/C/D/E (serologic tests), entero-haemorrhagic Escherichia coli, and amoebic liver disease (stool samples), and continued the treatment regime. On day 16 after disease onset (day 9 of antibiotic therapy), the patient’s condition improved, both his body temperature and his liver enzymes decreased. On day 14 of treatment (4 days ceftriaxone; 10 days meropenem), the patient had fully recovered (including complete normalization of laboratory parameters). One week after treatment, 3 stool samples (obtained on 3 different days) were negative for S. Typhi. During a family visit in Dresden 14 days after completion of initial treatment, the patient was hospitalised again (Department of Infectious Diseases and Tropical Medicine, Städtisches Klinikum Dresden) for high-grade fever, crampy abdominal pain, and watery diarrhoea. Abdominal ultrasound revealed extended mesenteric lymph nodes. The colleagues ruled out schistosomiasis and HIV (serology), as well as helminthic infections, other parasites, and Clostridium difficile (stool analyses). Blood cultures revealed S. Typhi (susceptibility testing: Table 2 ). Urine analysis, performed because of dysuria and pollakiuria, yielded a urinary tract infection (UTI) due to Escherichia coli (4-MRGN (German Classification of Gram-negative bacteria indicating resistance to 4 clinically relevant groups of bactericidal antibiotics: cephalosporine and acylureidopenicilline antibiotics, carbapenems and fluoroquinolones []), OXA-48 positive; Colony forming units: 106/ml). Consequently, the colleagues administered a combination antibiotic therapy according to susceptibility testing using intravenous ceftriaxone (2 g daily dose maintained for 28 days to address relapse) and oral sulfamethoxazole/trimethoprim (800/160 mg daily dose, maintained for 10 days to address the UTI). The patient fully recovered. Again, 3 stool samples following treatment were negative for S. Typhi. The patient has been free of relapse for 9 months.
pmc-6388817-1	A 29-year-old woman with a history of asthma (on intermittent inhaler use) came in with one episode of unarousable loss of consciousness. She was noted to have irregular breathing that alarmed the mother who was sleeping next to her. She called for help and the brother then tried to wake her up but she was not arousable. According to the account, she was sweating profusely and had labored breathing. She spontaneously started breathing normally and started coming around. At this point, she felt very weak, experienced nausea and vomiting, and felt like her “stomach was upset”. Her post-event recovery was less than five minutes. She was brought to the hospital. She is a nurse by profession and was doing her normal ward duties and reports no remarkable event in her history that would have suggested volume loss or prolonged hemodynamic stress. Her examination was unremarkable and there was no postural drop in blood pressure (BP). She was admitted under neurology; her blood and electrolyte work-up was normal and she underwent a complete neurological work-up. She was then referred to cardiology at which point it was noted that she had pre-excitation on the electrocardiogram (ECG). She was taken to the catheterization lab where she underwent an electrophysiological (EP) study that induced an orthodromic atrioventricular tachycardia. Atrial fibrillation was induced through rapid atrial pacing but could not be sustained and no ventricular arrhythmias were inducible without or with dobutamine provocation. Ablation of a left posteroseptal pathway was carried out. The earliest ventricular signal was tracked during tachycardia and ventricular pacing but ablation at the earliest position suppressed accessory pathway conduction only to recur every time. After extensively mapping the right side and the coronary sinus, the ablation was stopped. She was put on flecainide and calcium channel blockers and was discharged. After a few weeks, she had a similar episode and was brought to the hospital. She then underwent a head-up tilt (HUT) test on suspicion of vasovagal mechanism of syncope, which came out positive with nitrate provocation. Her post-ictal phase was reported by her to be an exact replication of her clinical symptoms. The flecainide and calcium channel blockers were discontinued as the mechanism of her fainting was identified to be vasovagal and not a cardiac arrhythmia. She was prescribed hydration, counter-maneuvers (which she practiced inconsistently), and preventive measures. Since the last episode, she has done well but experiences recurrences.
pmc-6388817-2	A 33-year-old woman, married with four children, presented to the clinic with a history of four episodes of unresponsiveness. Two were in an upright posture in the morning hours while she was preparing breakfast for her children. The other two were while she was sleeping and her husband discovered that her breathing pattern had become irregular. He tried to arouse her but could not do so. He reported that she was sweating profusely. She recovered in less than five minutes but was too weak to move and had abdominal cramps and a desire to defecate. The first such episode was short and she had not sought medical help. After the second episode, she was seen at a cardiology tertiary care center. Her exam and basic laboratory work were unremarkable. She did not have a postural drop in BP. Her ECG showed normal sinus rhythm with frequent ventricular ectopy of the right ventricular outflow tract origin. An echocardiogram revealed structurally normal heart with preserved left and right ventricular functions. In view of ventricular tachycardia as a cause of her syncope, she was offered an EP study and ablation. She was brought to the EP laboratory, where her rhythm was normal sinus rhythm and no ectopy could be induced despite isoprenaline provocation. She was then discharged on calcium channel blockers. At the time of her visit, she was doing well and had no ventricular ectopy. She underwent a HUT test which was positive with nitrate provocation. She stated that her symptoms on the HUT table were consistent with the ones that she had been experiencing during the episodes. She was prescribed hydration, counter-maneuvers and preventive measures. Since the last episode, she has not had any recurrence.
pmc-6388817-3	A 43-year-old man who is a hospital worker came to the clinic with three successive syncopal attacks, all in the morning hours. One was noted while he was supine and got up from sleep. He was sweating profusely according to him and it was witnessed by his wife. He felt nauseous and had an abdominal gripe and passed out while in bed. He recovered spontaneously after a few minutes while his wife tried to revive him. On examination, he did not have a postural drop in BP. His ECG was within normal limits and an echocardiogram was conducted which was normal. His blood and biochemical work-up were normal. He underwent a HUT test which was positive with nitrate provocation. He was reassured and sent home with advice to remain hydrated, apply counter-maneuvers and exercise. After his clinic visit, he had another episode of supine fainting and this time his wife raised his legs and he reports that despite experiencing the same symptoms, the duration of the episode was abbreviated. He has done well since the institution of regular hydration and exercising the counter-maneuvers, though he still experiences recurrent episodes.
pmc-6388817-4	A 51-year-old man presented to us with three episodes of loss of consciousness. He had an aortic valve replacement with a metallic valve a few years ago and did not have any other cardiac risk factors and was fairly active. He took warfarin and his international normalized ratio (INR) was within therapeutic range. The day of the admission, he has been out the whole day and had not eaten or taken the usual amount of liquids; the initiating event took place at a funeral, where he felt nauseous and dizzy. This was in the evening time. At night, he went to operate the water pump and had an unheralded fall and recovered spontaneously. He was brought up to his room where he lay with head propped up. At that time, he felt a griping pain in the abdomen and experienced nausea and passed out. According to the wife, he came around with sprinkling of water. He complained of worsening of the gripe and felt like vomiting. By this time he was totally lying flat in bed. The wife witnessed his eyes rolling up and he had myoclonic jerks. He came around in a couple of minutes and was rushed to the hospital. On examination, he has normal range pulse and BP, while the rest of the exam was unremarkable. His ECG (sinus rhythm with right bundle-branch block), blood work-up and echocardiogram were normal. His ejection fraction (EF) was 55% and the prosthetic aortic valve was functioning normally. His neurological assessment, electroencephalogram (EEG) and scan ruled out a neurologic cause (hemorrhage or thromboembolic event). He then underwent a HUT test, which came out positive at three minutes post nitrate provocation with a cardio-inhibitory response, where the ECG showed severe sinus bradycardia and sinoatrial (SA) exit block. He reproduced and confirmed all the clinical symptoms of an abdominal gripe, nausea, and sweating. He also felt like moving his bowel at the time. He was prescribed hydration, counter-maneuvers and walking. He did not have any recurrence in the follow-up period.
pmc-6388817-5	A 67-year-old man who was functionally very active, presented with a history of fainting while in bed lying flat. He had similar multiple episodes. The episodes were noted during sleep, where his breathing would become labored and he had difficulty being aroused from sleep. These episodes were during the period when he had “stomach flu”. The five noted episodes were spread over months. The last one was prolonged with longer recovery time, necessitating a hospital visit. He did give a history of upright syncope in his youth. He had a history of hypertension for which he was well controlled on calcium channel blockers and low dose hydrochlorothiazide. On admission, his pulse and BP were in range and there was no postural drop. His ECG, blood work-up and echocardiogram were normal. He also had a 24 hours Holter monitoring, which showed normal diurnal variation and appropriate nocturnal slowing and there was no episode of blocks or pauses. The neurologic clinical assessment and workup were normal for age. He underwent a HUT test, which revealed a sinus arrest with pause (nine seconds) after five minutes of nitrate provocation. He experienced sweating, nausea, and abdominal pain prior to syncope on the HUT test; during his phase, he showed sinus bradycardia. He was prescribed hydration and measures to take care of the trigger in time as well as counter-maneuvers (leg crossing and muscle tensing) and walking. He has been followed-up without recurrence.
pmc-6388818-1	This is a case of a 54-year-old divorced Caucasian male who has no prior psychiatric history or hospitalization. He was the lead singer of a local rock band. The patient has a 20-year history of cocaine abuse. He routinely uses cocaine prior to his stage performances. He reportedly binged on cocaine following a concert performance in a downtown bar. He snorted more cocaine than usual and immediately developed a severe headache and lower extremity numbness. He was rushed to the local emergency room, and an MRI of the brain without contrast was done. The MRI of the brain without contrast showed two small foci of increased signal intensity within the subcortical white matter of the left frontal lobe (Figure ). It also showed the finding of bilateral foci of infarct involving the right side of the pons (Figure ). Both figures are consistent with an embolic phenomenon. The patient has not complained of any somatic issues related to his cocaine use. The patient reported some depressive and anxiety symptoms as a result of the stroke but he remained optimistic about his recovery. He denied any vegetative depressive symptoms or suicidal ideations. He was initially seen by a nurse practitioner at the emergency room who diagnosed him with an adjustment disorder. After stabilization in the medical floor and a two-week stay at a rehabilitation program, the patient was sent home with good family support. Over the course of two weeks, the patient noted significant crying spells most of the day, nearly every day. He consistently denied that he was depressed and suicidal. His family became concerned and sent him to his primary care physician. The physician believed that he was suffering from depression because of his dramatic clinical presentation. The patient was eventually referred to the local mental health center by his primary care physician because of uncontrollable crying spells. He was not subjectively depressed but objectively tearful with a flat affect. He also complained of sleeping difficulties with ruminative worries about his situation. He denied any suicidal thoughts. The patient was started on Remeron (mirtazapine), 15 mg at bedtime. He also engaged in weekly psychotherapy sessions. Over the next two months, the patient noted improvements in his sleeping patterns and appetite. The crying spells persisted. The patient was observed to be tearful while at the waiting area, during the psychiatric evaluation, and after his treatment appointment. His family reports that he cries every day for no apparent reason. Despite reassurances that he was not depressed, the family was convinced that his emotional state was getting worse. The patient was eventually diagnosed with pseudobulbar affect (PBA) because of his repeated outburst of involuntary crying. The crying was occurring even though there was no sad event that triggered those emotions. These episodes were persistent and had occurred in different situations or settings. He was referred to a local neurologist who confirmed the PBA. Eventually, he was managed with dextromethorphan hydrobromide and quinidine sulfate (DM/Q), 20 mg/10 mg capsules twice a day, in addition to his mirtazapine. The patient's crying spells improved significantly after the DM/Q was started. He tolerated it very well with no complaints of any side effects. A year later, the patient had multiple tragedies in his family. His father, with whom he was very close with, suddenly and unexpectedly died. He also had an argument with his daughter, who later refused to talk to him. He was overwhelmed with financial problems. Because of these, the patient became more depressed and the crying spells recurred. Despite his medication compliance with DM/Q and mirtazapine, he noted worsening depression and occasional suicidal thoughts. He reported symptoms of sad mood, anhedonia, fatigue, excessive sleeping with early morning awakenings, increased appetite and weight gain, psychomotor retardation, and feelings of helplessness and worthlessness. He was having thoughts of shooting himself, even though he does not own a gun. This time, he was subjectively complaining of being "down in the dumps." He was seen in the emergency room for a crisis evaluation and referred back to the mental health center. He was reevaluated and his mirtazapine was switched to Viibryd (vilazodone) because of weight gain concerns. He also attended twice a week psychotherapy sessions. A month later, with these interventions, the patient's depressive symptoms, including the crying spells, had improved. He continues to receive his DM/Q and vilazodone and weekly psychotherapy sessions with no exacerbations of any mood symptoms.
pmc-6388819-1	A 67-year-old man with a past medical history of multiple myeloma, hyperlipidemia, and hypertension presented to the emergency department with two days of chest pain, shortness of breath, and orthopnea progressing to a single episode of loss of consciousness on exertion. He reported having similar symptoms over the past two weeks, but it has progressed in severity and had accompanied an episode of syncope in the last two days. Syncope is not preceded by any prodromal symptoms like dizziness, sweating, or autonomic symptoms. The patient denied fever, chills, nausea, vomiting, and abdominal pain. On physical examination, he appeared alert and in no acute distress. His heart rate was 84 beats per minute; blood pressure was 120/70 mmHg; respiration rate was 28 breaths per minute, and peripheral capillary oxygen saturation was 98%. Cardiac examination showed elevated jugular venous pressure, a systolic ejection murmur at the apex and left of the sternal border. The respiratory exam showed a bilateral inspiratory crackle. The other findings of his examination were unremarkable. Initial laboratory investigations showed normal white blood cell count, normal hemoglobin, and normal electrolytes. His pro-brain natriuretic peptide (BNP) was 1425 pg/mL (reference range, 1–100 pg/mL). Chest radiography showed pulmonary edema in the lower lung field of both lungs with some Kerley-B lines, as shown in Figure . EKG showed a right bundle branch block with low voltage in the limb leads and no ST-T ischemic change, as shown in Figure . Echocardiogram showed a markedly increased left ventricular (LV) wall thickness, hyperdynamic function with an ejection fraction of 75%, paradoxical motion of the interventricular septum with LVOT obstruction due to systolic anterior motion (SAM) of the mitral valve, and moderate mitral and tricuspid regurgitation, as shown in Figure . The results of genetic testing for HOCM mutations were negative. A constellation of findings on laboratory, EKG, echocardiogram, and magnetic resonance imaging (MRI) in the setting of the history of multiple myeloma led us to a presumptive diagnosis of acute decompensated diastolic heart failure with LVOT obstruction secondary to cardiac amyloidosis. Initial symptomatic treatment started by an elevation of the head of the bed and one dose of furosemide 40 mg and nitroglycerin 200 mcg/minute intravenously. For multiple myeloma, we continued treatment with cyclophosphamide, thalidomide, and dexamethasone. Beta-blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARB) were avoided due to concerns of symptomatic deterioration with these medications. After symptomatic control, the patient was scheduled for septal myotomy that helped in symptomatic improvement, and we placed an implantable cardiac defibrillator (ICD) to prevent any arrhythmias causing sudden cardiac death.
pmc-6388847-1	An 82-year-old obese woman presented to the dermatology department because of a two-month history of an enlarging umbilical mass that had been bleeding. The patient also complained of menorrhagia for the previous two weeks. Physical examination showed a 2 cm firm, non-tender, protrusive umbilical nodule (Figure ). Laboratory studies showed moderate anemia and a high human epididymis protein 4 (HE4) marker. The Risk of Ovarian Malignancy Algorithm, or ROMA score, classified this patient at high risk for malignant disease. An abdominopelvic ultrasound examination showed a right ovarian mass and a right parauterine teratoma. A solid hypo-echoic mass in the umbilicus without any sonographic features of inflammation involving the adjacent soft fatty tissue was suggestive of an SMJN, and led to a search for the primary tumour and other metastases []. Histological and immunohistochemical examination of the umbilical mass biopsy diagnosed a high-grade serous ovarian carcinoma. Histological/cytological evaluations of all umbilical lesions are mandatory, not only to determine its nature but also to guide the clinician in searching for the possible primary source []. Further assessment with MRI confirmed the diagnosis and detected a lymph node metastasis in the right external iliac group. The patient subsequently underwent a hysterectomy and bilateral salpingo-oophorectomy. The patient declined chemotherapy as she found this treatment approach too aggressive.
pmc-6388848-1	We report a 50-year-old male patient who was admitted to our emergency department after falling from a height onto his elbow. On physical examination, his elbow was swollen and tender. The active and passive elbow range of motion was painful and limited. The neurovascular examination of the upper extremity was normal. Direct radiographic examination of the elbow showed a distal humeral fracture with comminution of the capitellum and lateral column (Figure ). In order to understand the extent of the comminution, computerized tomography (CT) imaging was performed. The CT examination showed fragmentation of the capitellum and a fracture extending to the lateral column (Figure ). Surgical fixation of the fracture was planned based on imaging findings. Under general anesthesia and tourniquet control, a posterior surgical approach with olecranon osteotomy was used for the exposure of the fracture. The articular surface was reduced and fixed with two 2.7 mm diameter magnesium bioabsorbable screws (MAGNEZIX® CS, Syntellix AG, Hanover, Germany). The lateral column was fixed with an anatomic lateral column plate. It has been paid attention that the two materials (titanium and magnesium) did not touch each other physically. The olecranon osteotomy was fixed with the tension band wiring technique (Figure ). After the operation, the patient was immobilized in an above-elbow plaster cast for 10 days to facilitate the subsidence of edema around the elbow. Thereafter, the plaster cast was removed and the active elbow range of motion exercises was initiated. At the first month follow-up, the elbow range of motion was between 20 and 110 degrees. Supination and pronation of the forearm were in the normal range. At the fourth-month follow-up, the fracture was united and the elbow range of motion was nearly normal, between 5 degrees and 130 degrees (Figure ). The Mayo elbow performance score was 100.
pmc-6388854-1	A 60-year-old male with metastatic RCC treated with nivolumab and palliative radiation therapy presented to our institution in 2016 with shortness of breath and was found to be in acute respiratory failure. Computed tomography (CT) of the chest was significant for multiple new ground-glass opacities throughout bilateral lungs concerning for therapy-induced pneumonitis (Figures , ). The etiology of ground glass opacities includes but is not limited to infectious pneumonitis, bronchioloalveolar carcinoma, or interstitial disease. Given the timing of symptom onset as well as lack of response to infectious treatment, therapy-induced pneumonitis remained high on our differential. He initially presented in 2011 with gross hematuria and right-sided flank pain and underwent right radical nephrectomy and lymph node dissection of a 9 cm Fuhrman grade IV RCC with negative margins and lymph nodes. Two years later, surveillance imaging and biopsy were significant for metastatic RCC in the lungs. He was initially treated with one year of sunitinib, a multi-targeted receptor tyrosine kinase inhibitor. However, given the progression of disease, he was transitioned to one year of pazopanib followed by six months of axitinib, one month of everolimus, and five months of sorafenib. Pazopanib, axitinib, and sorafenib are also tyrosine kinase inhibitors. Everolimus is an inhibitor of mammalian target of rapamycin. Given the lack of response to these therapies, our patient was started on nivolumab at 3 mg/kg in May of 2016. Over the course of four years, he received targeted palliative radiotherapy including 1900 centigray (cGy) to a left upper lobe lung mass in May 2016 and 800 cGy to an L5 lesion in September 2016. He complained of chronic shortness of breath for three months felt secondary to anemia and a left pleural effusion before presenting to our hospital in acute respiratory failure with CT evidence of new diffuse ground-glass opacities occupying the majority of both lungs (Figures , ). Given high suspicion for therapy-induced pneumonitis, he was started on a treatment course of high dose steroids. However, the patient’s respiratory status continued to decline and he passed away on comfort measures. Pathology was significant for organizing diffuse alveolar damage with hyaline membrane formation in all lobes of both lungs away from the metastatic RCC (Figures , ). There was no evidence of an infectious process from cultures and pathologic evaluation. This histologic reaction pattern is a typical finding in patients with a clinical diagnosis of acute respiratory distress syndrome (ARDS) concerning for therapy-induced pneumonitis.
pmc-6388873-1	We present a case of a 50-year-old Caucasian male who presented to the emergency department with complaints of lower abdominal pain, fever and sweating. On examination, the patient had tenderness to palpation in the right iliac fossa, with significant rebound tenderness and guarding. Body temperature was recorded at 38.5°C. The patient's past medical history was significant for an incident of similar pain six months prior to presentation. He was diagnosed with sigmoid diverticular disease confirmed by computed tomography (CT) scan and managed conservatively. A subsequent colonoscopy confirmed the diagnosis, and did not reveal any other colonic pathology. Further investigations revealed a raised white blood cell count of 16,000 per microliter. CT scan of the abdomen and pelvis disclosed evidence of extensive free gas under the right dome of the diaphragm confirming suspicion of a perforation. Fluid-filled prominent loops of small bowel were noted. However, none of them were dilated to suggest obstruction. Mild bowel thickening was also noted around the cecum. Pneumatosis coli suggestive of ischemic bowel, extending from the cecum to the proximal ascending colon was seen. A blind ending structure with calcifications was also seen (Figure ). Other significant findings on the scan included a liver cyst, consistent with the patient’s previous CT scan, and consolidation at the base of the right lung. Subsequently, the patient underwent an emergency laparotomy and a diffuse four-quadrant peritonitis was seen. A giant perforated MD, 80 cm proximal of the ileocecal valve was identified as the cause of the peritonitis. The giant MD measured approximately 10 cm in length and 2.5 cm in width (Figure ). A small perforation at the tip of the MD was observed. No other intraabdominal pathology was identified, in particular, there was no evidence of colonic ishchaemia. Resection of the segment of small bowel bearing the MD was performed with a side-to-side stapled anastomosis. Pathologic examination showed a T-shaped length of bowel, 6 x 5 x 3 cm in maximal dimension, with a 3 x 5 x 6 cm portion of mesentery attached. The presumed diverticulum was 5 cm long with a maximal inner circumference of 5 cm. The perforation measured 0.2 cm and the lumen of the specimen was stained green. No heterotropic tissue was identified. Post-operative recovery was uneventful and the patient was discharged on oral antibiotics.

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