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pmc-6303965-1	A 69-year-old man presented to the outpatient clinic of the Department of Breast Surgery at the Shiga General Hospital (Moriyama, Shiga, Japan) with a lump in his left breast in the 1990s. Physical examination revealed a mass measuring > 6 cm without skin invasion in the upper-lateral region as well as axillary lymph node swelling. The patient had a history of diabetes, hyper tension, cerebral infarction, and brain schwannoma controlled by oral glimepiride 0.5 mg, nifedipine 40 mg, and aspirin 100 mg. He had no remarkable family history. Ultrasonography showed a breast mass and right-sided axillary lymph node swelling. A core needle biopsy was performed, and the tumor was diagnosed as a high histological grade invasive ductal carcinoma. It was ER-positive, PgR-negative, HER2-negative and AR-positive (detected by anti-AR rabbit monoclonal antibody SP107; Roche tissue diagnostics, Ltd.); the Ki-67 labeling index was 10% (Fig. ). The tumor was radiologically classified as cT3N3M0, stage IIIC disease (Union for International Cancer Control-TNM classification, 8th edition) []. Preoperative chemotherapy was not performed at the time; thus, a mastectomy and axillary dissection were performed. The final histological diagnosis was pt3n3a (36/39) M0, stage IIIC disease. Postoperative chemotherapy with epirubicin 40 mg/body with 5-fluorouracil (5-FU) 500 mg/body every 2 weeks plus oral cyclophosphamide 100 mg daily (CEF) was administered. After 2 cycles of the chemotherapy, computed tomography (CT) revealed pleural metastasis in his right lung. Anti-estrogen therapy with high-dose toremifene (TOR) 120 mg b.i.d and oral 5-FU, doxifluridine (5’DFUR) 1200 mg was administered as first-line therapy for metastatic breast cancer. Two years after the recurrence, the patient complained of frequent urination. Radiological and histological examinations revealed that he had cT3N0M0, stage III primary prostate cancer (Fig. ) with a prostate-specific antigen (PSA) level of 40.5 ng/mL. He underwent radiation therapy at a dose of 66.0 Gy/33 fractions as local control to treat the prostate cancer. After radiotherapy, the prostate cancer therapy was temporarily suspended, and the watchful waiting approach was taken. Breast cancer therapy with high-dose TOR was continued since breast cancer control was good. Six months later, the PSA level increased from 3.7 ng/mL to 18.0 ng/mL. Oral estramustine phosphate sodium hydrate (Estracyt®) 626.8 mg was administered daily because this drug remains specifically in prostate cancer tissue and is not contraindicated in patients with breast cancer. The PSA level immediately decreased to within the normal range (3.7 ng/mL), and Estracyt® as well as TOR were continued for 3 years until the patient experienced a deep vein thrombosis in his right leg related to the endocrine therapy, while the antiplatelet therapy was ongoing. TOR was stopped but Estracyt® was continued for symptomatic disease control. A CT scan revealed liver metastasis from the breast cancer after the patient stopped the breast cancer therapy. Estracyt® was changed to the non-steroidal anti-androgen agent, Casodex® as the second-line endocrine therapy for the prostate cancer and a luteinizing hormone-releasing hormone (LHRH) agonist as third-line treatment; however, the patient died due to breast cancer progression 5 years after the diagnosis of prostate cancer (Fig. ). We retrospectively reviewed the medical records of 1431 patients with breast cancer who underwent breast cancer therapy at the Shiga General Hospital between 1998 and 2017. The retrospective review of the medical records was approved by the appropriate ethics review board, and the study complied with the tenets of the Declaration of Helsinki. Of all patients, 8 (0.6%) were men; they were diagnosed with primary breast cancer histologically. Table shows the clinicopathological characteristics of the patients with MBC.
pmc-6303969-1	A 57-year-old female patient presented in our clinic with complaints of occasional pain, numbness and paralysis in her left hand and a palpable, painless mass in the ulnar side of her left elbow for the last 2 months. There was no history of trauma. Besides the discomfort in the left elbow, the patient had a history of lumbar disc protrusion and hypertension, which was well controlled with medication. No other medical related history could be traced. Physical examination showed a painless mass (about 1 cm*2 cm) in the ulnar side of her left elbow with no inflammation. Neurologic examination revealed light numbness on the ulnar side of her left hand and fingers. No pathological sign was detected positive. Electromyography (EMG) showed the ulnar nerve across the elbow was injured. Magnetic resonance imaging (MRI) disclosed a subcutaneous irregular abnormal signal in the upper ulnar side of left forearm, hyperintense on T1and T2-weighted image which was considered to be a benign lesion, and joint effusion in the left elbow (Fig. ). X-ray showed degenerated change in the left elbow joint. Laboratory studies revealed the routine blood test, tumor markers, erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein were all within normal range. The mass was considered to be a cystic form disease which compressed the ulnar nerve. With the guidance of ultrasound, we first located the cyst. Precise puncture and aspiration were made with a 18G biopsy needle (Gallini, Italy) to evacuate mucinous material inside the cyst. The mass deflated mostly and the patient experienced an evident release of the pain with no significant improvement in other symptoms. Three months later, the patient came to the clinic complaining the recurrence of symptoms of numbness and paralysis which still tremendously affected her daily life. Further evaluation indicated that open surgery was inevitable. The ulnar nerve was then surgically explored along its trajectory with a curve incision. The ulnar epineurium at cubital tunnel was thickened and the tunnel was constricted. After careful dissection, ruptured cystic wall was disclosed within nerve fibers (Fig. ). Full excision of the cystic wall was performed and a sample of the lesion was sent for frozen section. Distal constriction of the ulnar nerve by fat and vascular tissue was discovered and complete decompression was operated. External neurolysis of the ulnar nerve was carefully done together with anterior subcutaneous transposition to relocate ulnar nerve on the soft tissue bed. Histopathology revealed that the sample was fiber tissues in cystic wall (Fig. ). Reporting diagnosis was intraneural ganglion cyst. The patient was evaluated 2 weeks after the surgery with improvement in motor function and some minor alleviation in dysesthesia. Follow-up of 2 years showed complete release in the symptoms and the latest MRI imaging revealed no sign of recurrence.
pmc-6303972-1	The patient is a 19-year-old man, a seasonal agricultural worker daily in contact with sheep, living in Burgundy and with no history of travel neither abroad nor in the south of France during the previous months. At the end of September 2016, the patient performed farm work in contact with sheep when he had an ocular traumatism caused by a fly. Three hours after the ocular traumatism, the patient complained of a painful right eye discomfort, with sensation of moving foreign. Upon arrival at the department of ophthalmic emergency of the University Hospital Center of Dijon within hours of the onset of the first symptoms, the clinical examination showed a red and irritated conjunctiva in the right eye with the observation of mobile and translucent larvae in the conjunctival fornix. The rest of the ophthalmologic examination was normal. Eight larvae were extracted using Bonn hook forceps under local anesthesia. All larvae were sent to the Parasitology-Mycology Laboratory of the University Hospital Center of Dijon for identification. The parasitological diagnosis allowed the identification of stage 1 Oestrus ovis larvae (L1). Indeed, the macroscopic examination revealed larvae of white color and about 1 mm length. Microscopically, these larvae were composed of eleven metameres, each of these displaying 4 rows of spines (Fig. a). The cephalic segment had two large black buccal hooks (Fig. b), while the posterior segment consisted of two tubercles, each containing about ten curved spines (Fig. c) which is concordant with the morphological description of L1 Oestrus ovis larvae in the literature []. At the first visit, the patient received a local treatment based on the administration of oxybuprocaine and antiseptics (Biocidan®) as eye drops. The curative treatment consisted of the mechanical removal of all of the eight larvae present at the level of the conjunctiva using a forceps, as mentioned before. Subsequently, the treatment was supplemented by the administration of antiseptic eye drops (i.e. desomedine) and antibiotics (i.e. ofloxacin). Removal of the larvae resulted in rapid relief and no complication was further reported.
pmc-6303979-1	A 32-year-old woman, 3G2P (2 normal vaginal delivery, no abnormality) was referred to our hospital at 25 weeks of gestation for evaluation of a tumorous lesion located near the neck of the fetus, which was detected at gestational week 23. Prenatal three-dimensional ultrasonography performed at gestational week 25 showed a giant tumor around the neck and face (Fig. a). The spatial relationship between the tumor and the oral cavity was not confirmed; however, the possibility of an epignathus was strongly suspected. A prenatal ultrasound at gestational week 26 revealed a polyhydramnios, a giant tumor around the neck, and an intracranial tumorous lesion (Fig. b). Color Doppler ultrasonography showed arterial branches assumedly from the right internal carotid artery running into the giant tumor around the neck. Arterial branches from the right middle cerebral artery were suspected to be running into the intracranial lesion. These potential feeding arteries were of concern, because they could raise difficulties in the control of bleeding during an ex utero intrapartum treatment (EXIT) procedure. Magnetic resonance imaging (MRI) performed at gestational week 25 showed a giant tumor around the neck with heterogeneous iso-to-low signal density on T1-weighted images, and iso-to-high signal density on T2-weighted images. MRI also suggested a connection between the giant tumor and the intracranial lesion (Fig. c). An epignathus with intracranial extension was suspected. The possibility of preterm labor was a concern; therefore, supportive care with amnioreduction was to be provided until the fetus attained a certain weight and stage of organ development for performance of a cesarean delivery, at approximately 30 gestational weeks. At gestational week 27, after the amnioreduction was performed, a placental abruption occurred, and the fetus was delivered by emergency cesarean section. Chromosome analysis was not performed. The fetus was stillborn, and an autopsy was performed after 27 h, for pathological diagnosis and assessment of the intracranial lesion. The fetus weighed 1228 g. At dissection, an epignathus was observed protruding from the mouth (Fig. a). It was a large, reddish, multicystic tumor measuring 12 × 6 × 6 cm and weighing 270 g. Neither a cleft palate nor cleft lips were found; however, there was a defect in the soft palate, within which the base of the epignathus was located (Fig. b). Upon opening the skull, an intracranial tumor weighing 14 g was detected in the middle cranial fossa. It was covered by a thin capsule, and there was no invasion into the brain (Fig. c). The tumor had a very short stem, 2 mm in diameter, which was located on the right side of the sella turcica. There was no tumor involvement in the optic foramen, foramen ovale, or optic nerve. After removal of the upper portion of the tumor above the stem, a small hole was found, measuring 2 mm in diameter, at the base of the sella turcica (Fig. d). To avoid facial and cranial deformation, in consideration of the distress of the bereaved family, we did not make further incisions through the bone, but rather, confirmed the continuance of the epignathus and intracranial tumor by using a sonde. The spreading of the epignathus into the cranium was consistent with the clinical ultrasonographic evaluation. Macroscopically, the epignathus was a large multicystic tumor, containing white solid parts and cysts filled with serous or bloody fluid (Fig. a-c). Calcification was also seen. Microscopically, the prominent component of the tumor was immature neuroepithelial tissue (Fig. a). Immature neural tubules were seen, lined by dark hyperchromatic columnar cells with stratification and frequent mitoses, and were accompanied by glial tissue. Other components included melanocytes, retinal tissue, exocrine glands, skin, hepatocytes, renal glomeruli, lung tissue, glandular epithelium with goblet cells, squamous epithelium, cartilage, bone, adipose tissue, and smooth muscle (Fig. b-d). The intracranial tumor was macroscopically white and soft (Fig. d). The thin capsule was ruptured while we were excising the tumor at autopsy. Microscopically, the majority of the tumor was immature neuroepithelial tissue (Fig. a). The main components were immature neural tubules lined by dark hyperchromatic columnar cells with stratification and mitoses, and were accompanied by glial tissue. Other components included choroid plexus, aggregation of hepatocytes with extramedullary hematopoiesis, exocrine glands resembling pancreatic acini, columnar glandular cells resembling gastric foveolar epithelium, squamous epithelium, cartilage, and calcification (Fig. b-d). The main components of the oral and intracranial tumors are summarized in Table . Both the epignathus and intracranial lesion were composed of three germinal layers, with immature neuroepithelial tissue being the most predominant. Pulmonary components seen in the epignathus were equivalent to a canalicular stage of development, which was immature as compared to the saccular stage of the fetus’s internal lungs (Fig. ). We, therefore, made the diagnosis of epignathus with intracranial extension, histologically showing immature teratoma. As for the internal organs of the fetus, histological findings associated with hypoxia were seen. There was a great increase in weight seen in the liver and adrenal glands. Histologically, the liver showed congestion and marked hematopoiesis. Erythropoiesis usually diminishes and myelopoiesis becomes only faintly apparent in the liver by 28 weeks []; however, in our case, both erythropoiesis and myelopoiesis were marked in the liver as well as in the spleen. Furthermore, increased hemosiderin deposition was seen, not only within the periportal spaces, but also in surrounding hepatocytes. The cortices of both adrenal glands showed adenoid changes, with focal hemorrhaging. These findings in the liver and adrenal glands indicate hypoxic stress. The lungs weighed a little less than is typical with respect to the gestational week; however, histologically they had developed into the saccular stage. Because the kidneys and lungs were in the normal stage of development, the fetus could have swallowed some amniotic fluid in utero in spite of having the epignathus. Altogether, above-mentioned findings support the determination that an airway obstruction induced by the epignathus was the direct cause of death. The remainder of the detected organs (heart, thymus, gastrointestinal tract, gallbladder, pancreas, uterus, and ovaries) had developed sufficiently for the gestational week. The weight of the organs with means and standard deviations [] are shown in Table . The placenta weighed 840 g and was histologically normal, except for the retroplacental hematoma, which was consistent with the clinical episode of placental abruption.
pmc-6303981-1	A 27-year-old woman (height 165 cm; weight 92 kg) was admitted to hospital for management of a 1.8 cm × 1.3 cm × 1.7 cm renal mass in the lower pole of the right kidney (examined by MRI) and scheduled for laparoscopic partial nephrectomy under general anesthesia. The patient mentioned she had no other medical history but congenital asymptomatic platybasia. The laboratory examinations were normal except uric acid 425 μmol/L (the normal range is 90–360 μmol/L). There was no abnormity for electrocardiogram (ECG) or chest X-ray. On the operating day, the patient entered the operating room without premedication. ECG, SpO2, end-tidal carbon dioxide pressure (PetCO2) and bispectral index (BIS) were monitored. A 20G catheter was inserted into her left radial artery to ensure real-time blood pressure monitoring. Anesthesia was induced with remifentanil (target-controlled infusion at effect-site concentration of 3 ng/mL), 150 mg propofol and 50 mg rocuronium. A 7 mm ID endotracheal tube was intubated with an insertion distance of 21 cm at the incisors. The patient was ventilated with volume controlled ventilation mode (setting tidal volume at 500 ml, respiratory rate at 12 times/min, inspiration and expiration ratio at 1:2) and was placed in the left lateral decubitus position. Before pneumoperitoneum, airway pressure was controlled within 20 cmH2O and PetCO2 was controlled between 31 and 35 mmHg. Anesthesia was maintained with intravenous remifentanil (target-controlled infusion at effect-site level of 2–3 ng/mL), propofol (constant infusion), and 60% nitrous oxide balanced with oxygen. Sufentanil (totally 20 μg) and cisatracurium (totally 2 mg) was intermittently injected intravenously and the infusion speed of propofol was adjusted according to BIS within the range of 40 to 60. The procedure was uneventful though there was an episode. After finishing the first trocar portal, a balloon, made from a sutured latex glove, was used to inflate and dilate retroperitoneum cavity. But the balloon was ruptured during inflation and the suture on the balloon was left in retroperitoneum space. Finally, the suture was found and removed after a period of searching with the help of laparoscopy. Procedure was performed via 3 successfully established trocar portals. The retroperitoneal space was hydrostatically dilated and CO2 was insufflated to a pressure of 14 mmHg. During the procedure, the airway pressure increased to 30 cmH2O and PetCO2 was elevated to 41 mmHg. SpO2 remained 100%. We adjusted tidal volume to 550 ml and respiratory rate to 13 times/min. At the end of the surgery, the retroperitoneal carbon dioxide was retreated and airway pressure decreased to 23–24 cmH2O. Operative duration was almost 90 min, during which the hemodynamic parameters were stable. We stopped all intravenous anesthetics and changed the gas supply to 100% O2 with a flow rate of 5 L/min. The patient woke up quickly and could respond to instructions. Then the patient was placed to supine position. Mechanical ventilation was ceased and the patient had spontaneous breathing. Antagonists of muscle relaxant (neostigmine 2 mg plus atropine 1 mg) were given. Two minutes after the stop of mechanical ventilation, SpO2 decreased rapidly to 30% and blood pressure decreased from 120/79 mmHg to 93/65 mmHg. The patient was unconscious. We conducted manual ventilation immediately and then SpO2 returned to 85–90%. Meanwhile, blood pressure recovered. Immediate auscultation showed decreased breath sounds on the right side of chest and the left side was normal. Immediate arterial blood gas analysis showed PCO2 75 mmHg, PO2 83 mmHg. We woke up the patient and she could breathe spontaneously with better tidal volume. We extubated her endotracheal tube and provided oxygen via facemask. She was able to breathe without distress but felt right chest pain. SpO2 climbed to 91–93% gradually. Point-of-care chest X-ray was performed, demonstrating a large, right pneumothorax occupying 70% of the hemithorax (Fig. ). The patient was transferred to post-anesthesia care unit and stayed for 1 h with facemask oxygen inhalation (oxygen flow rate 5 L/min). Her vital signs were normal during the period and SpO2 returned to 100%. She felt right chest pain relieved a bit. Arterial blood gas was re-examined and all parameters were in normal range. The patient was later sent back to general ward. In general ward, respiratory and hemodynamic parameters of the patient remained stable during hospital stay. Chest X-ray taken on the first post-operative day revealed complete re-expansion of the right lung (Fig. ). She claimed no chest pain and no other symptoms. The patient was discharged home on postoperative day 5.
pmc-6303989-1	We describe a 61-year-old Arab man who retired from teaching 2 years ago. He did not smoke tobacco or consume alcohol. His past medical history included two surgical operations: a hydatid cyst of the liver operated on 6 years ago in a surgery department and a right ureteral lithiasis operated on in our urology department 4 years ago (at that time, he had only been explored by an intravenous pyelogram). He had been under alpha blocker for benign prostatic hyperplasia for 6 months. He was admitted for a suspicious renal cyst, incidentally found on renal and vesicoprostatic ultrasound. He had no complaints. His physical examination was unremarkable. His temperature was 37.2 °C, his blood pressure was 134/82 mmHg, and his pulse rate was regular at 74 beats per minute. On laboratory values, white blood cell count was 7.9 × 103/mL, red blood cell count 4.1 × 106/mL, hemoglobin 14.2 g/dL, platelets 396 × 103/mL, creatinine 1.04 mg/dL, sodium 138 mEq/L, potassium 4.1 mEq/L, and C-reactive protein 1 mg/L. Urines examination showed no leukocyturia or bacteriuria. Renal and vesicoprostatic ultrasound found a non-vascularized cystic formation with a thickened and irregular wall on his left kidney. An abdominal computed tomography (CT) scan revealed a 38 mm left renal mid-pole lesion, isodense to the renal parenchyma. Dynamic CT showed an early intense and peripheral enhancement and nonenhanced central zone even in the delayed phase (Fig. ). The renal artery and vein appeared normal. No metastases were demonstrated. We also recovered a CT realized 6 years ago in the surgery department, which illustrated the same lesion but 10 mm smaller (Fig. ). For further characterization of the cyst, a magnetic resonance imaging (MRI) was performed. It revealed a lesion with thickened and irregular wall (from 3 to 10 mm) isointense on T1-weighted images and hypointense on T2- weighted images with intense enhancement. The central zone was hypointense on T1 and hyperintense on T2 with no enhancement (Fig. ). Radiological findings concluded a Bosniak IV cyst. As this cyst type is considered clearly malignant, our patient was accordingly scheduled for surgery. A partial nephrectomy was considered technically difficult for this lesion, so he underwent an open left radical nephrectomy. His postoperative course was uneventful. On gross examination, cut sections divulged a well-defined medio-renal hemorrhagic and brownish mass measuring 3 × 2.5 cm. Histological examination of the mass showed a mesenchymal proliferation arising from the wall of a large vessel and developing within its lumen. It was composed of hyalinized papillary and anastomosing channel-like structures that were lined by flat to plump endothelial cells with no atypia or mitotic activity (Fig. ). An immunohistochemical study revealed diffuse staining of tumors cells for CD-31 and negativity for HMB-45 and cytokeratin (Fig. ). The diagnosis of IPEH was retained. He was asymptomatic and no recurrence of the tumor has been detected during 9 years of regular clinical and radiological follow-up. Additional file presents a timeline of the case.
pmc-6304004-1	A 15-month old boy, without significant medical history, was presented at the Burn Centre after a scald burn from hot milk, with mixed deep second degree burns to lips and chin, neck, chest, left arm and left foot covering 12% total body surface area (TBSA; burns to neck (1%); chest (4%); face (3%); foot (1%); left arm 3%) as assessed by palmar method. The mechanism of injury was submersion by just-boiled milk falling off the table, after he pulled the tablecloth the mug was standing on. There was no history of ingestion and no scalding or swelling of tongue or nostrils. He was cooled at the place of injury and assessed by the Helicopter Emergency Medical Services (HEMS). Intravenous rehydration according to Parkland formula (lactated ringers: 4 ml/kg/% TBSA of which half in the first 8 h, the remaining volume in the subsequent 16 h, with a maintenance of 2 ml/kg/h NaCl 0.9%/glucose 5%) was initiated and intravenous analgesics were given (fentanyl 1.5 mcg/kg and paracetamol 15 mg/kg). He had a progressive stridor with laboured breathing which the HEMS-physician ascribed to sputum stasis. With supplemental oxygen (non-rebreathing mask 12 L/min) his oxygen saturation was more than 95%. Hence he was considered medically stable during transport by the HEMS-physician. Upon first presentation at the Burn Centre he had deteriorated, his oxygen saturation was 80% despite maximal supplemental oxygen via a non-rebreathing mask. Inspection showed blistering off the lower lip concomitant with his burn injuries, without intra-oral redness or swelling (Fig. ). His circulation was not compromised. Despite airway opening manoeuvres and sputum evacuation, the stridor persisted. Due to persistent respiratory distress the decision was made to intubate. Pre-oxygenation took place by non-rebreathing bag (already in situ) and bag-mask ventilation after induction. Due to vomiting a rapid sequence induction was performed. Induction of anaesthesia was obtained with propofol 2.5 mg/kg, ketamine 1 mg/kg, fentanyl 3 mcg/kg and rocuroniumbromide 1 mg/kg. Bag-mask ventilation proved impossible due to airway obstruction. Classic airway opening manoeuvres and a guedell were ineffective. Direct laryngoscopy revealed a considerably enlarged and oedematous epiglottis without visible vocal cords. Blind intubation with a cuffed endotracheal tube (4,5 mm) was successful with help of a malleable stylet. Afterwards, ventilation was achieved with low pressure and bilateral air entry. The algorithm for difficult airway management would have been pursued in case of intubation failure by attempting videolaryngoscopy, emergency needle cricothyrotomy or a surgical airway. This algorithm was discussed with the entire emergency team prior to first intubation. All equipment, as well as expertise, necessary for a management of a difficult airway is present in the emergency room of the Burn Centre. After securing the airway, the burn injuries were debrided and dressed in silver sulfadiazine gauze. Rehydration in accordance with Parkland formula was maintained. Subsequently, he was transported to a paediatric intensive care unit in an academic paediatric hospital for continuation of mechanical ventilation. The otorhinolaryngologist performed a direct laryngoscopy, demonstrating a fibrinous coating around the evidently oedematous epiglottis. Three days after initial intubation, the patient extubated himself. Because of a manifest inspiratory stridor and increased respiratory labour, he was reintubated via rigid fiberscopy in the operating theatre by an experienced otorhinolaryngologist. Rigid fiberscopy was his preferred method since he lacked experience with videolaryngoscopy. There was still evident swelling of the epiglottis (Fig. ). Five days after intubation, fiberoptic laryngoscopy demonstrated a restored airway with a thin epiglottis, pale arytenoid cartilage (post-burn injury) and residual fibrinous coating in the postcricoid region, upon which the patient was successfully extubated (Fig. ). For an overview of this case’s timeline, see Fig. .
pmc-6304189-1	A 22-year-old Caucasian female, nulligravida, presented to our institute (a tertiary referral center) complaining of a slowly growing painful mass at the right lateral neck. Past medical history included a resected desmoid tumor with free surgical margins from the same region six months ago in another center (). No other comorbidities were reported. Her family history included mother with systemic lupus erythematosus. Physical examination revealed a hard, tender, palpable mass over the upper half of the right SCM, painful head rotation, and right upper extremity extension but no other sensory deficits or motion restrictions. MRI revealed an enhancing mass at the cephalic third of the SCM, in close contact with the right IJV, with no signs of vessel infiltration (). No pathologic cervical lymph nodes were detected by MRI and ultrasound tomography. Given her past medical history, imaging findings, and clinical presentation, the patient was scheduled two months later for surgical excision of the tumor recurrence under general anesthesia. Access to the surgical field was via an oblique right lateral neck incision. The neoplasm was found to originate from the upper portion of the SCM, extending to the parapharyngeal space, and infiltrating the SAN (). A wide excision was performed, including the upper two-thirds of the SCM, the tumor extension to the prestyloid parapharyngeal space, the stylohyoid muscle, and part of the styloid process. The completely thrombosed ipsilateral IJV was ligated and excised. Intraoperatively, it was deemed impossible to dissect the SAN free from the neoplasm and so it had to be sacrificed. However, remaining length of the nerve was satisfactory, and a microsurgical end-to-end anastomosis was performed (). A close suction drain was placed, and the wound was closed in layers. Patient recovery from the operating room was without any incidents. The patient was discharged on the second postoperative day in good condition. The range of right upper extremity extension was limited, and the patient was referred for physiotherapy. Microscopically, the tumor consisted of fascicles of uniform elongated fibroblast-like cells, surrounded and separated by abundant collagen, with no cell-to-cell contact. Neoplastic cells had sharply defined nuclei with one or more delicate nucleoli and poorly defined cell borders often merging with the extracellular collagen. Regenerative multinucleated skeletal muscle cells were found in the periphery of the lesion. Mitotic activity was typically low (2 mitoses per 10 HPFs) without atypical mitoses. Immunohistochemically, neoplastic cells stained vimentin (), smooth muscle actin (), and desmin () and were negative for CD34. β-Catenin nuclear staining was also present (). The index of proliferation Ki-67 was 1-2%. Focally close excision margins were noted at the parapharyngeal border of the biopsy specimen. On the 3-month postoperative follow-up, no clinical signs of tumor recurrence were noted, and the right upper extremity mobility was satisfactory, indicating successful anastomosis of the SAN. Unfortunately, on the 6-month follow-up, local pain and swelling indicated new tumor recurrence which was confirmed by MRI. The case of our patient was brought to the Oncology Board. Unanimously, it was agreed that a wait-and-see policy was not a sound option and some kind of treatment should be administered since the tumor recurred within six months. Based on imaging findings, excellent performance status of the patient, and our experience as a tertiary referral center on head and neck surgery, excision of the new tumor recurrence was considered as the primary treatment modality. RT was also recommended, but given its long-term side-effects and the proximity of neural structures to the tumor bed, it was considered as an alternative option. Cytotoxic agents, tyrosine kinase inhibitors, and hormonal therapy were considered but discarded, given the reproductive age of our patient and the absence of contraindications for surgery or RT. The patient declined the option of further surgery but elected for RT and received 54 Gy of external beam RT over six weeks. Treatment was well tolerated. After the completion of RT, complete clinical remission of the disease was noted. No evidence of recurrence has been detected on clinical evaluation and imaging studies after twelve months of follow-up.
pmc-6304206-1	A 21-year-old, G0P0 woman presented with a four-month history of excessive and prolonged bleeding per vagina, as well as a palpated mass at the lower abdomen that was rapidly increasing in size. Her past history was unremarkable. Two months before this visit, she had presented at the provincial hospital with severe anemic symptoms. She was found to have severe anemia and received a blood component transfusion. The excessive vaginal bleeding had persisted until one month prior to her presentation at our hospital. She had undergone endometrial curettage at the provincial hospital, and the pathological report indicted an atypical round cell tumor. Upon presentation at our hospital, she was pale and found to have a midline pelvic mass. Per vaginal examination revealed a 3 cm exophytic mass at the posterior lip of the uterine cervix and a 14 cm, firm uterine mass. Hematoxylin-eosin stained (H&E) slides of the endometrial specimen were reviewed. The sections showed a malignant round cell tumor with scattering foci and vascular architecture mixed with benign-looking endometrial glands. Computed tomography (CT) of the abdominopelvic region showed an enlarged, well-defined uterine border with diffused enhancing thickening in the endometrial cavity involving entire uterine body and cervix (). The overall uterine size was 15.0x11.6x10.5 cm. Intra-abdominal lymphadenopathy and ascites in the pelvic cavity were noted. The liver, gallbladder, pancreas, spleen, bilateral kidneys, and bilateral adrenal glands appeared normal. A biopsy of the cervical mass was performed to obtain tissue for further study of immunohistochemical (IHC) markers. The pathological examination showed a malignant small round cell tumor suggestive of metastatic sarcoma of uterine origin. Immunohistochemical studies showed negative staining for multi-cytokeratin (AE1/AE3), S-100 protein, CD 10, cyclin D1, caldesmon, myogenin, and desmin. The patient's tumor exhibited focal positive staining for smooth muscle actin. The preoperative differential diagnoses were HG-ESS and UUS. At laparotomy, the uterus and obturator lymph nodes on both sides were enlarged. There were multiple nodules in the cul-de-sac. Neither the adnexae nor the omentum appeared remarkable. The surgical procedures included total abdominal hysterectomy, bilateral salpingo-oophorectomy, resections of enlarged pelvic nodes, omentectomy, and biopsy of peritoneal nodules in the cul-de-sac. Macroscopically, the uterus weighed 714.67 grams and measured 13x13x7 cm with an intracavitary polypoid mass that occupied the entire endometrial cavity (). The tumor had invaded the serosa of the uterus and ectocervix. Sectioning revealed a yellow cut surface with focal areas of hemorrhage. Histologically, the tumor exhibited a permeative growth pattern and was composed of uniformly high-grade round cells with brisk mitotic activity arranged in tight nests separated by a delicate capillary network (). The tumor had invaded the uterine serosa, and there was extensive lymphovascular space invasion (LVSI) (). Sections of the pelvic lymph nodes on both sides and peritoneal nodule revealed multiple metastatic foci. The omentum, both ovaries, and both fallopian tubes were histologically unremarkable. Additional IHC studies revealed positive diffuse staining for vimentin, CD 10, and cyclin D1. The tumor stained negative for desmin, estrogen receptors (ER), and progesterone receptors (PR). A diagnosis of HG-ESS stage IIIC was made based on these pathological findings. The postoperative clinical course was uneventful. The patient was started on adjuvant chemotherapy consisting of Adriamycin (50 mg/m2) and Ifosfamide (5 g/m2) given every three weeks. After receiving four courses of this chemotherapy regimen, the patient refused further adjuvant chemotherapy due to her inability to tolerate the side-effects. Pelvic radiation was then administered thereafter. Despite undergoing radiation treatment, the patient experienced rapid disease progression and succumbed eight months after operation.
pmc-6304208-1	A 28-year-old primigravida woman was referred to our hospital for the evaluation of a suspected fetal cranial abnormality at 17 weeks of gestation. There was an unremarkable medical history and family history and no history of drugs or substance abuse. 2D ultrasound images (Voluson E8; GE Medical Systems, Zipf, Austria) revealed the absence of calvarium with deformed brain tissue directly exposed to the amniotic cavity, suggestive of exencephaly (). The fetal spine also showed the absence of vertebral posterior elements with splaying of the lamina at the thoracic level (). The lower limbs appeared to be fused in fixed extension with two femora and two tibiae (); however, we were not able to identify whether there were one or two feet. The fetal kidneys and urinary bladder were visualized as normal, and the amniotic fluid was normal. Color Doppler showed a single umbilical artery. 3D rendering images using 4D ultrasound with HDlive mode clearly revealed the absence of calvarium with deformed and degenerated brain tissues, consistent with exencephaly (). The spine also showed extensive clefts in the posterior part of the fetal vertebrae from the upper cervical region to the sacrum (). These findings were consistent with those of craniospinal rachischisis totalis (anencephaly with rachischisis totalis). The lower extremities were completely fused, and the feet were fused with the heels, which were immobile (). Absence of the right upper limb was also identified (). Thus, the diagnosis of sirenomelia with anencephaly, rachischisis totalis, and absence of the right upper limb was made prenatally. The parents were informed about the findings and the associated poor prognosis; they then opted for termination of pregnancy, which was performed at 18 weeks of gestation. External examination of the fetus revealed anencephaly with craniorachischisis totalis (), fused lower limbs (), nine toes with a fused bilateral thumb (), absence of the right upper limb () and external genitalia, and imperforate anus, almost coinciding with the observation on the 3D sonographic rendering images. The autopsy imaging by radiography demonstrated complete rachischisis (). The single lower limb contained two femora and two tibiae with some metatarsals and phalanges ().
pmc-6304209-1	An 18-year-old man was referred to our outpatient clinic because of unique MRI findings. MRI was performed by another physician because the patient exhibited tremor in both hands, which began 1 year earlier. However, this tremor did not affect his quality of life. His father had also exhibited a similar tremor in both hands for many years. There was no history of previous health problems. The patient did not complain of headache, fever, arthritis, or skin rash. He had no behavioral, psychiatric, or cognitive complaints. There was no history of vaccination or infection history before the MRI was performed. Detailed neurological examination of the patient revealed only bilateral postural tremor in his hands. No aphasia, apraxia, cortical sensory disturbance, or visual field defect was detected upon examination. MRI revealed a tumefactive edematous lesion in the left frontal area, which was hypointense on T1-weighted images, and hyperintense on T2-weighted and fluid attenuation inversion recovery (FLAIR) images. After gadolinium administration, T1-weighted images demonstrated ring enhancement. Hyperintense lesions were observed in the subcortical and deep white matter in the right hemisphere on T2-weighted and FLAIR images (). Spinal MRI was normal. Complete blood count, erythrocyte sedimentation rate, and levels of biochemical parameters, including glucose, urea, creatinine, lactate dehydrogenase, activities of alanine aminotransferase, and aspartate aminotransferase, were normal. Vasculitis screening tests for ANA, ANCA, anti-DNA, anti-Ro, and anti-La were negative. The anti-HIV 1/2 test was also negative. Cerebrospinal fluid (CSF) analysis revealed a normal cell count, as well as normal levels of protein and glucose; oligoclonal bands were observed in the CSF that were absent from in the serum. Anti-NMO and anti-MOG antibodies were negative. Thoracic computed tomography and abdominal ultrasonography were normal. Studies of visual evoked potential revealed prolonged P100 latency in the right eye. The optical coherence tomography was normal and the contrast sensitivity was also normal. Neuropsychological examination was performed to determine the cognitive dysfunction. The Stroop test, PASAT-3 (Turkish), and BICAMS battery (symbol digit modality test, SDMT; California verbal learning test-II, CVLT-II; brief visuospatial memory test revised, BVMTR) were used to assess cognitive performance. His PASAT-3 score was 60/60. Stroop test, SDMT, CVLT-II, and BVMTR scores were within normal values. A 10-Hz symmetric tremor was recorded with surface electromyography (EMG) from the forearm flexor and extensor muscles. Clinical and electromyographic features and positive family history supported an essential tremor diagnosis. The tremor was not associated with demyelinating lesions in MRI images and was therefore regarded as an essential tremor. The patient was not treated and underwent radiological follow-up. Follow-up MRI performed one month later revealed an improvement of the tumefactive lesion in the left frontal area. However, a new tumefactive lesion with perifocal edema, which demonstrated ring-like gadolinium enhancement on T1-weighted images and peripheral restriction on DWI, was observed in the right frontal area (). One year later, a follow-up brain MRI showed regression of the tumefactive lesion, as well as two new hyperintense lesions on T2-weighted and FLAIR images in the bilateral parietooccipital areas. After gadolinium administration, peripheral contrast enhancement was observed in the lesion on the left side (). Spinal MRI was normal. The patient was monitored without treatment. One year later, a follow-up was conducted, which revealed that he had not developed any obvious neurological symptoms. Written informed consent was obtained from the participant for the publication of this case report.
pmc-6304231-1	A 49-year old Arabic housewife presented at our hospital for abdominal pain and distention. Her medical history was unremarkable apart from uterine myomectomy 17 years earlier. The patient did not smoke or drink alcohol. On admission, she had no fever, her body temperature was 37.5° C, her pulse rate was 70 beats/minute, and her blood pressure was 120/80 mmHg. The result of her neurological examination was normal. Her laboratory test results were within normal limits (especially the complete blood count and liver and renal function). The patient’s physical examination showed a distended abdomen with a large tumor extending from the pelvis to the umbilical area. An abdominal computed tomographic (CT) scan was obtained, which showed a 14-cm uterine malignant tumor. Also, the CT scan revealed a 4-cm isolated splenic nodule suggesting a metastatic lesion. The tumor was limited to the uterus and did not extend beyond. The patient underwent radical surgical treatment consisting of total hysterectomy, total splenectomy, and lymphadenectomy. The macroscopic examination of resected specimens showed a huge, whitish, friable tumor occupying the entire uterine cavity, as well as a 4-cm splenic nodule with irregular contours, fibrous consistency, and a heterogeneous aspect (Figs. and , respectively). The histopathological analysis disclosed a uterine clear cell carcinoma invading the outer half of the myometrium with negative lymph nodes, classified as stage IB according to the International Federation of Gynecology and Obstetrics classification scheme (Fig. a and b). The tumor cells were disposed in irregular trabecular and solid structures with abundant granular amphophilic to clear cytoplasm and rounded nuclei. The tumor cells were negative for estrogen and progesterone receptors and positive for cytokeratin AE1/AE3. The splenic lesion consisted of multiple confluent and variably sized fibrotic nodules centered by many vessels. These vessels were surrounded by areas of hemorrhage, fibroblasts, and hemosiderin-laden macrophages (Fig. a and b). The immunohistochemical analysis of the splenic lesion showed that these vessels had three distinctive immunophenotypes corresponding to splenic red pulp vessels: CD34+/CD8−/CD31+, CD34−/CD8−/CD31+, and CD34−/CD8+/CD31+, respectively (Figs. a, b and ). These histopathologic features were consistent with SANT. The patient had no signs of the disease 17 months after the surgical treatment.
pmc-6304235-1	A 65-year-old Chinese man was hospitalized in November 2012 for epistaxis since the previous month. Indirect nasopharyngoscopy revealed a scarlet mass with a rough surface in his left nasopharyngeal cavity. A clinical examination revealed no lymph node enlargement. He underwent surgery. A pathological examination indicated a mucosal melanoma in his left nasopharyngeal cavity. The results of computed tomography (CT) and MRI examinations showed that there was no metastasis to other organs. This patient was hospitalized again in March 2013 to undergo adjuvant treatment, including IFN-α2b treatment, radiotherapy, and chemotherapy. A high dose of IFN-α2b (20 MIU/m2 per day) was administered for 5 days, then radiotherapy was performed 14 times (total 28 Gy), followed by a low dose of temozolomide (75 mg/m2 per day) for 3 weeks. On the third day of IFN-α2b treatment, our patient began to develop simple episcleritis in his left eye. He experienced symptoms of severe eye pain, hyperemia, and edema on the lateral sclera and conjunctiva of his left eye. The redness was diffuse, and it covered a pie-shaped area confined to the outer quadrant (Fig. ). We performed the phenylephrine blanching test to diagnose episcleritis. Episcleritis may be differentiated from scleritis by using phenylephrine eye drops, which cause blanching of the blood vessels in episcleritis, but not in scleritis. The percentage of CD3+ T cells in lymphocytes from blood was increased after IFN-α2b treatment (Fig. ). After approximately 6 days, the symptoms of eye pain, hyperemia, and edema disappeared gradually. The treatment of IFN-α2b had been stopped when the symptoms disappeared. After radiotherapy was performed three times, our patient again developed episcleritis in his left eye, but it was limited to the inner quadrant. The same symptoms of hyperemia and edema occurred again (Fig. ); CD3+ T cell frequency was also at a higher level (Fig. ). After approximately a week, all the symptoms disappeared completely, and the treatment with radiology was still on-going. Simple treatment involving topical ofloxacin and phenylephrine was administered during the two periods of episcleritis. Whether the occurrence of these two episodes of episcleritis is associated with treatment of IFN-α2b and radiotherapy is of interest and worth studying. This patient was followed up to detect late metastasis or recurrence for the first 2 years after surgery and the adjuvant therapy, and no metastasis or recurrence was found.
pmc-6304476-1	We report the case of a 23-year-old male with T-cell ALL undergoing treatment with Hyper-CVAD that presented initially with blurry vision. Upon presentation in August 2016, the patient was 19 days status after treatment cycle 1B of his Hyper-CVAD therapy. His hemoglobin level was 10.5 mg/dL and his platelet count was 63 K/μL on presentation in the eye clinic. On examination, the patient was found to have best corrected Snellen visual acuity of 20/20 in the right eye (OD) and 20/25 in the left eye (OS). Anterior segment examination of both eyes (OU) was unremarkable. Fundoscopic examination OU revealed multiple peripapillary cotton wool spots in both eyes (Figures and ). There was no evidence of hemorrhage or leukemic infiltration. At this time, observation was recommended. In mid-September 2016, 18 days after Hyper-CVAD treatment cycle 2B, the patient presented with decreased vision OS for one week. His hemoglobin level decreased to 7.4 gm/dL from 10.5 gm/dL prior to his most recent treatment cycle and his platelet count decreased to 5 K/μL from 63 K/μL. Despite clinical evidence of regression of the leukemia, he was found to have best corrected Snellen visual acuity of 20/20 OD and light perception OS. Anterior segment examination was within normal limits in both eyes. Fundoscopic examination revealed retinal hemorrhages extending from the peripapillary region into the midperipheral retina OU (Figures and ), with a large premacular hemorrhage in the left eye. The premacular hemorrhage was a well-organized clot at the time. Observation was recommended. However, upon follow-up one week later, the examination revealed discrete layering of the premacular hemorrhage. At that time, a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser was used to disrupt the posterior hyaloid face. As a result, the hemorrhage was free to diffuse into the vitreous cavity and settle inferiorly (). The patient's vision returned to baseline immediately after the procedure. During the entire course of treatment, the patient did not receive any platelet and/or blood transfusions. However, his hemoglobin level improved to 9.4 gm/dL and platelet count to 43 K/μL two months later. The remaining retinal hemorrhages resolved over several months () and the patient completed the remainder of his Hyper-CVAD therapy without further ocular complications. Of note, there were no further episodes of severe anemia or thrombocytopenia.
pmc-6304482-1	An 81-year-old woman with multiple medical comorbidities, significant for atrial fibrillation and anticoagulated with dabigatran 150 mg twice a day, presented with acute on chronic kidney injury in the setting of volume overload. Dabigatran was started two years prior. Her medical profile also included coronary artery disease, stage 2A chronic kidney disease, insulin dependent diabetes mellitus, hypertension, asymptomatic chronic lymphocytic leukemia, hypothyroidism, and a stable pulmonary nodule. Her medications included aspirin 81 mg once a day, amlodipine 5 mg once a day, losartan 150 mg once a day, hydrochlorothiazide 37.5 mg once a day, bisoprolol 7.5 mg once a day, nitroglycerin patch 0.4 mg from 8 a.m. to 8 p.m. per day, metformin 500 mg four times a day, insulin glargine 70 units twice a day, insulin Humalog 30-60 units as per sliding scale three times a day with meals, and levothyroxine 125 microgram once a day. She did not have significant alcohol or smoking history. The patient presented with a one-week history of progressive dyspnea. She denied cough, fevers, chills, or sick contacts. Review of systems was otherwise unremarkable. On presentation, she was hypoxemic, oxygen saturation ranging from 88% to 92% on 6L of oxygen via nasal prongs. She was hemodynamically stable, afebrile and the remainder of her vital signs was within normal limits. On examination, her jugular venous pressure was measured at 6 cm above the sternal angle. There were no murmurs, extra heart sounds, heaves, or thrills. She had bilateral pitting edema of her legs extending to the knees. Auscultation of the lungs revealed decreased breath sounds bilaterally with coarse crackles. The remainder of her physical examination was otherwise unremarkable. Initial labs showed leukocytosis of 16.8 (reference range: 4-10 X 109/L) (see ) with a lymphocyte count of 11.3 (reference range: 0.5-3.3 X 109/L), neutrophil count of 5.4 (reference range: 2.0 – 9.0 X 109/L), and monocyte count of 0.2 (reference range: 0.0 – 1.0 X 109/L). Hemoglobin was 118 g/L (reference range: 123-157 g/L); platelets were 217 (reference range: 130-400 X 109/L) (see ). Her BNP was elevated at 5741 (reference range for age > 75: 300 – 1800 ng/L) (see ). Serum creatinine was 177 umol/L (reference range: 40-100 umol/L) with an eGFR of 23 mL/min/1.73 m2 (reference range: ≥ 60 mL/min/1.73 m2). At baseline, serum creatinine was 91 umol/L with eGFR 57 mL/min/1.73 m2. Electrolytes were within normal limits (see ). INR was elevated at 1.6 (reference range: 0.8 – 1.1) with an elevated activated Partial Thromboplastin Time (aPTT) of 50 seconds (reference range: 28-38 seconds) (see ). Chest x-ray showed interstitial pulmonary edema with stable cardiomediastinal contours. There were trace pleural effusions. Transthoracic echocardiogram showed normal biventricular size and systolic function. Ejection fraction was > 60%. There were mild left ventricular hypertrophy and no valvular disease. The patient was diuresed with furosemide 40 mg IV twice a day for a total dose of 80 mg IV within the first day and placed on fluid restriction of <2 L/day. Her dyspnea and hypoxemia resolved within 24 hours. However, her serum creatinine continued to increase. Her serum creatinine rose from a baseline of 91 umol/L (reference value: 40-100 umol/L) to 177 umol/L on day of admission and reached 618 umol/L within 7 days of hospitalization (). Furosemide was discontinued after the first day of admission. With the rise of creatinine, fluid restriction was discontinued and instead, isotonic intravenous fluids were administered, with no change in serum creatinine. She was referred to the nephrology service for assessment of acute kidney injury. Renal replacement therapy was initiated via a central venous catheter and intermittent hemodialysis. Dabigatran was held. Urinalysis demonstrated cloudy and brown-colored urine, but no gross hematuria by inspection. Microscopic analysis showed >30 dysmorphic red blood cells/high powered field, protein > 5 g/L, and white blood cells (WBC) > 5/high powered field, while leukocyte esterase and nitrites were negative (see ). Before this hospitalization, there was no evidence of hematuria or proteinuria on urinalysis. Renal ultrasound showed bilateral, mild increase in renal parenchymal echogenicity, suggesting medical renal disease. There was no hydronephrosis. Fractional excretion of sodium (FeNa) was 1.1%. Anti-Streptolysin O titer was 449 IU/mL (reference values: 0-200 IU/mL) and serum IgA was 5.85 g/L (reference values: 0.60-4.20 g/L) (see ). Complement levels, C3 and C4, were normal (see ). Antinuclear antibodies, anti-double stranded DNA antibodies, anti-cyclic citrullinated peptide antibodies, anti-glomerular basement membrane antibodies, cytoplasmic anti-neutrophil cytoplasmic antibodies (c-ANCA), and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) were normal (see ). Serum free light chains ratio (kappa: lambda) was also mildly elevated at 3.16 (reference values: 0.26-1.65) (see ). Albumin to creatinine ratio was 15.37 mg/mmol (reference value <2.29 mg/mmol). HIV and hepatitis serology were negative. The patient underwent a diagnostic kidney biopsy, which showed extensive red blood cell casts within tubular lumen as well as tubular epithelial cell injury on light microscopy (Figures and ), without evidence of acute glomerulonephritis (Figures and ). Electron microscopy showed subepithelial “hump-like” deposits most of which were located within the mesangial notch areas, and thus, thought to be resolving postinfectious glomerulonephritis (). Immunofluorescence microscopy was negative for IgA and IgG, but trace positive for C3 (). The findings were most consistent with anticoagulant-related nephropathy with concurrent resolving postinfectious glomerulonephritis. The patient had a protracted stay in hospital. During her admission, she was found to have enterococcus faecium urinary tract infection which responded to vancomycin and subsegmental pulmonary emboli treated with unfractionated heparin. She did not have recovery of her renal function and continued intermittent hemodialysis.
pmc-6304483-1	A 62-year-old man presented at the Neurology consultation with a six-week history of a severe, strictly left orbitotemporal headache, with a frequency of three attacks per week, occasionally more than one at the same day. Most of them occurred in the first half of the night, waking him up, and lasted between thirty minutes and one hour. He used to take ibuprofen as acute treatment, with unsatisfactory response, since he did not notice a significant difference between treated and untreated attacks in terms of duration and pain intensity. To relief the pain, he used to open the window to get some fresh air. The headache was always associated with ipsilateral conjunctival injection and lacrimation. Pain triggers were not identified by the patient. He had no personal or familial history of headaches. His medical history was remarkable for hypertension and asthma, with a past surgical history including septoplasty and bilateral middle turbinectomy and uncinectomy due to nasal respiratory insufficiency. By the time of medical evaluation he was asymptomatic and neurological exploration was unremarkable. The clinical picture was suggestive of a CH and the patient was medicated with verapamil 120 mg daily. A MRI scan was performed, which revealed a sphenoid sinus mucocele, without secure expansion of the sinus. Two weeks later the patient came to the Emergency Department with complaints of horizontal diplopia that he noted when he woke up in that morning. He maintained the headache attacks, with similar characteristics, despite prophylactic therapy. Neurological examination revealed left eye adduction palsy and ptosis. A brain CT scan was performed and excluded lesions other than the mucocele. Paranasal sinus MRI revealed molding of the medial wall of left cavernous sinus by the sphenoid mass (). A paranasal sinus CT scan was also performed to allow for a better characterization of the lesion, showing sclerosis and interruption of the roof and posterior wall of the left sphenoid hemisinus (). The patient was submitted to surgical drainage of the mucocele by transnasal-transphenoidal approach, with complete resolution of the adduction impairment, persisting a mild left eye ptosis. After the surgery the attacks stopped, and in the six-month follow-up he reported no further attacks.
pmc-6304506-1	A 44-year-old previously healthy male was taken to our ED by ambulance with acute agitation and fever. He had no family or personal history of psychiatric issues or psychosocial stressors that could have caused a psychotic episode. His family explained that he had been complaining for three days about a severe headache and fever and had acutely presented incontinence, agitation, and violent behavior two hours prior to the visit. On admission, the patient displayed bizarre, incorporative and violent behavior against medical staff. Since nonphysical strategies against agitated behavior referred to as “verbal deescalation” were unsuccessful, we required immediate action to protect the patient as well as medical staff from imminent harm using deep sedation. The Richmond Agitation Sedation Scale was graded as +4. Physical restraint and administration of sevoflurane and propofol allowed for further assessment assuring the safety of the patient and medical staff. His vital signs were remarkable for an isolated fever of 37.8°C associated with Kernig's sign. The patient did not have oral or genital ulcerations or an erythematous rash. His blood test results showed elevated white blood cell count of 16,990/μL with 80.1% neutrophils and C-reactive protein of 19.05 mg/dl. Blood gas analysis showed metabolic acidosis with a pH of 7.306, base excess -6.5 mmol/L, and lactate 7.5 mmol/L. Toxicological screening was negative. Cerebrospinal fluid examination revealed an increased cell count with monocyte dominance (126/uL). Computed tomography scan of the head was unremarkable. Fluid attenuated inversion recovery magnetic resonance imaging showed a high intensity signal in the sulci of the left parietal lobe and bilateral occipital lobe (Figures and ). As infectious meningoencephalitis was suspected, empirical therapy was immediately started with meropenem, vancomycin, acyclovir, methyl-prednisolone, and immunoglobulin. After erythema of the lower leg was noted on day 2, the patient recovered in seven days uneventfully without neurological defect. The erythema was pathologically proved as erythema nodosum. The patient thereafter reported that he had been experiencing recurrent episodes of oral ulcers throughout the last 20 years. Based on the findings including positive human leucocyte antigen (HLA) B-51, clinical manifestations, and the effectiveness of methylprednisolone, the diagnosis of NBD was made and remitted by maintenance of steroid therapy.
pmc-6304509-1	A 19-year-old Omani female not known to have any significant medical history was referred to our hospital with a history of upper abdominal discomfort more localized to the epigastric region and associated with jaundice and dark urine. There was no history of fever or night sweat nor history of travel. On physical examination, the patient was jaundice; otherwise, the systemic examination was unremarkable. Complete blood count was within normal limits with a normal white blood count (6.3 10∗g/L). Liver function test revealed a picture of obstructive jaundice with a total bilirubin of 52 umil/L, Alkaline phosphatase 302 [iU] /L, and Alanine transaminase 457 [iU]/L. QuantiFERON-Tb gold test was positive. CT scan of the abdomen and pelvis showed a lobulated and heterogeneous liver hilar mass with a central necrosis, measuring 2.4 x 3.9 cm. The mass was obstructing the proximal common hepatic duct resulting in dilatation of the intrahepatic biliary tree (). The mass was associated with multiple enlarged peripancreatic, porta hepatis and hepatoduodenal lymph nodes, measuring up to 1.2 cm. None of the lymph nodes were showing central necrosis. Features were suggestive of a cholangiocarcinoma of the common hepatic duct. Further work-up with a liver MRI redemonstrated the porta hepatis mass. The mass was T2 hyperintense and T1 hypointense and showed moderate enhancement on postcontrast sequence with severe diffuse restriction (Figures and ). On MRCP, the mass was causing severe narrowing of the proximal 1.8 cm of the common hepatic duct, reaching the confluence and causing moderate dilation of the intrahepatic biliary tree. In addition, the MRI revealed multiple foci of restriction scattered throughout the liver and some of them showed subtle enhancement on postcontrast sequence suggestive of liver microabscess ().Constellation of MRI findings was suggestive of localized TB of the porta hepatis; however, neoplastic lesion such as rhabdomyosarcoma and lymphoma could not be excluded and further evaluation with a tissue biopsy was advised. Chest radiograph was normal. Tumor markers were within normal limits including Cancer Ag 19-9 (CA 19-9): 8U/mL (range, 0-37U/mL), Carcinoembryonic antigen (CEA): 1.2 ug/L (range, 0-3ug/L), Alpha fetoprotein: 1.1 ug/L (range 0-15), and Chromogranin A: 47ug/L (range 26-92ug/L) The patient underwent laparoscopic biopsy and was found to have enlarged porta hepatis lymph nodes. Biopsy was taken from the porta hepatis mass and histopathological examination showed a granulomatous inflammatory process. Although, no definite proof was obtained by culture or polymerase chain reaction (PCR), probable TB diagnosis was made based on the histological and imaging findings, and the patient was treated for 6 months with Rifampicin 150 mg and Isoniazid 75 mg. The patient showed significant response to treatment with dramatic improvement of liver function test. A follow-up liver function test 3 months after starting anti-TB medication showed normalization of Alkaline phosphatase 91 [iU] /L along with improvement of total bilirubin of 24 umil/L and Alanine transaminase 211 [iU]/L. After completion of anti-TB medication, liver function test was back to normal with a total bilirubin of 17 umil/L, Alkaline phosphatase 58 [iU] /L, and Alanine transaminase 16 [iU]/L. A follow-up CT abdomen was performed 10 months later and showed complete resolution of porta hepatis mass and intrahepatic biliary dilatation along with significant regression of previously noted enlarged upper abdomen lymph nodes.
pmc-6304513-1	A 51 year old man presented to the ED for the third time in 2 weeks with complaints of flank pain and hematuria. He had complained of left sided flank pain during the initial 2 visits. During the first visit, the patient was diagnosed to have renal colic. X-ray KUB did not show any renal stone. He was treated symptomatically with analgesia and discharged. During the second visit with complaints of persistent left flank pain despite taking analgesia given at discharge, he was admitted to the emergency observation ward for pain management. Bedside ultrasound done then was noted to have mild left sided hydronephrosis. He was pain free at the end of the observation and was then discharged with analgesia and an outpatient follow-up with the urology department. He was also scheduled to have an outpatient computed tomography scan of the kidneys, ureters, and bladder (CT KUB). However, 2 days before the scheduled CT, he represented to the ED with right sided flank pain since morning on the day of his visit. The pain radiated to the right groin and was associated with hematuria. He was not passing blood clots. He denied any other complaints of fever, weight loss, vomiting, diarrhea, or constipation. He had a past medical history of hypertension, diabetes mellitus, and hyperlipidemia. He had previous surgeries for appendicectomy and cholecystectomy. His vital signs were stable. There was tenderness over the right flank on physical examination. There was also a palpable tender mass measuring about 5x5cm over the right lumbar region. There was no renal angel tenderness. Bedside ultrasound in the ED showed an appearance of a 6 cm cystic lesion around the inferior pole of the right kidney with internal echogenicity within the cyst. The provisional diagnosis was a bleeding renal cyst versus a tumor. Blood tests done in the ED showed a mildly elevated white cell count 12.64 × 10(9), hemoglobin of 14 gm/dL, and creatinine of 109 Umol/L. Patient was seen by the urology on-call in the ED and his bedside ultrasound done by the urologist revealed a 10 cms cystic lesion anterior to the lower pole of the right kidney with irregular internal echogenicity. Patient was admitted to urology department for further evaluation and management. Inpatient CT Intravenous Pyelography (IVP) was done and the left kidney showed relative hypoenhancement and reduced excretion of contrast, associated with diffuse ureteric thickening and periureteric fat stranding which could be related to a passed left renal calculus or a differential diagnosis of ureteropyelonephritis which was less likely due to diffuse involvement of left kidney. There was a tubular cystic structure in the right flank with inferior tip at the same site of previously inflamed appendix stump base which could represent mucocele of the appendix stump (). Patient was then transferred under the care of the general surgery department, where he underwent a colonoscopy which demonstrated an extrinsic compression at the caecum and appendiceal orifice and a smooth pedunculated polyp measuring 10 mm in the sigmoid colon (). Exploratory laparotomy was done, the mucocele was resected, and patient recovered well. Histopathology revealed a benign mucinous cystadenoma. The patient was discharged well with an outpatient surgical follow-up.
pmc-6304514-1	A 63-year-old man presented to his primary care physician in 2017 for a routine visit and was noted to have left lower lobe rhonchi. He reported that 6 months earlier, he started having wheezing during exercise which improved with time. Review of systems was negative otherwise. His medical history was significant for follicular thyroid cancer (FTC) treated with total thyroidectomy in 1977 followed by 30 mCi of radioactive iodine (RAI) in 1978. He did not have a history of neck irradiation or a family history of thyroid cancer. He had levothyroxine withdrawal I-131 whole body scan (WBS) in 1984 and 2002 that showed no evidence of residual or metastatic disease. Thyrogen stimulated WBS in 2010 was also unremarkable. He had multiple neck ultrasounds (last in 2014), that did not show any residual thyroid tissue or evidence of local recurrence. Tg levels, including stimulated, were always undetectable with negative anti-thyroglobulin antibody (TgAb). His TSH was maintained less than 2 uIU/ml on levothyroxine 112 mcg daily. The patient was discharged from Endocrinology in 2014 after 37 years of follow-up indicating excellent response to therapy. A chest X-ray ordered to evaluate the abnormal respiratory finding showed a left paraspinal/periaortic mass. Chest CT showed a 5.3 cm x 3.7 cm x 5.4 cm heterogeneously enhancing left infrahilar mass with occlusion of the left lower lobe bronchus and bilateral pulmonary nodules measuring up to 1 cm on the right and 0.9 cm on the left. He underwent bronchoscopy with endobronchial ultrasound and transbronchial lymph node aspiration. The cytology revealed metastatic FTC. The tumor cells were positive for thyroid transcription factor 1 (TTF-1), cytoketatin-7, focally positive for Tg, negative for cytokeratin-20, synaptophysin, chromogranin, and P63, consistent with thyroid primary malignancy. Thyroid ultrasound showed no evidence of residual thyroid tissue or local cancer recurrence. PET-CT showed a 3.9 cm x 3.7 cm x 5.2 cm FDG avid left lower lobe mass and bilateral indeterminate sub-centimeter non-FDG avid masses (). Tg measured by Beckman immunometric assay was undetectable with negative TgAb. Left pneumonectomy and intra-thoracic lymphadenectomy were performed. Final pathology revealed metastatic carcinoma of thyroid with a mixture of well-differentiated FTC (70%) () and anaplastic thyroid carcinoma (ATC) () components. The tumor showed perineural and angiolymphatic invasion. Nine lymph nodes were negative for malignancy. Tumor cells were negative for V600 BRAF mutation. The pathology was reviewed by a second institution which noted that the less differentiated tumor appeared to be poorly differentiated thyroid carcinoma (DTC) rather than ATC. The slides were sent to a national referral center (Defense Health Agency, Silver Spring, MD) which reported that the poorly (DTC) contained within it a small component positive for TTF-1 and negative for Tg, possibly consistent with ATC. Postoperative chest CT, two months following his diagnosis, showed minimal increase in the size of the right pulmonary nodule. He was treated for presumed ATC with two cycles of Doxorubicin and Docetaxel starting 3 weeks post-operatively. Further chemotherapy was held due to reduction in ejection fraction. RAI could not be used due to repeated administration of iodinated contrast. Patient declined entry in clinical trials. Repeat chest CT 2 months after chemotherapy showed stable lung nodules and a new 4 mm right lung nodule.
pmc-6304521-1	A 68-year-old woman presented with a three-week history of mild confusion and anomic aphasia. Her past medical history was significant for remote papillary thyroid cancer and scalp radiation for ringworm. A noncontrast CT of the head found extensive left frontoparietal vasogenic edema with mass effect of the underlying brain parenchyma and a left frontal mass-like density (). An MRI of the head demonstrated a large mass in the left frontal lobe with thick enhancing borders and a 9-mm left-to-right midline shift (). A CT of the chest, abdomen, and pelvis performed that day showed lymphadenopathy behind and above the left renal vein with the dominant node measuring 1.7 cm (). The patient underwent a left frontal craniotomy and microsurgical tumor removal. Pathology of the specimen revealed a large metastatic carcinoma of Müllerian origin with enlarged nuclei and nucleoli, abundant mitosis, and intraluminal necrosis (Figures and ). The tumor was positive for PAX-8 and CK7 by immunohistochemistry. One month later, the patient underwent a total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and cystoscopy. Intraoperative findings were notable for a darkened area on the right fallopian tube fimbria which was concerning for malignancy. The abdominal survey was otherwise normal (). Final pathology revealed high grade serous carcinoma identified only at the fimbrial end of the right fallopian tube, measuring 0.6 cm (Figures and ). By immunohistochemistry, the tumor was positive for p53, PAX-8, and WT-1 and negative for TTF-1. The patient underwent fractionated stereotactic radiotherapy to the left frontal resection cavity. Patient received a cumulative dose of 30 Gy in 5 fractions. After completing radiotherapy, she began adjuvant chemotherapy with 6 cycles of carboplatin AUC of 6 every 21 days and paclitaxel 80 mg/m2 weekly. She developed grade 3 neutropenia and was switched to carboplatin AUC of 5 and paclitaxel 150 mg/m2 every 21 days for cycles 5 and 6. She later received genetic testing using a 19-gene breast and ovarian cancer panel which was negative for mutations. She had a complete response to adjuvant treatment with a CA 125 of 22 and negative imaging.
pmc-6304522-1	A 63-year-old postmenopausal woman presented with deepening of voice, and increased hair growth on her face and lower abdomen over the past few months. She noticed thinning of her hair a few years ago. She was sexually active up until last year. She complained of decreased libido, disturbed sleep, back pain, right ear deafness and urge incontinence for years. She had a 36-year-old son and a 33-year-old daughter. She developed menopause on early 50s. Past history included hypertension, obstructive sleep apnea, tonsillectomy, and tubal ligation. She had family history of chronic kidney disease, hypertension, malignant neoplasm of urinary bladder, malignant melanoma of skin, myelodysplastic syndrome, and sudden death. On clinical examination, blood pressure was 132/76 mmHg and heart rate was 64/m. She was anxious and overweight (BMI: 38.06) with enlarged thyroid gland, clitoromegaly, male pattern baldness (significant loss of scalp hair) and hirsutism. Laboratory reports showed normal urea (27 mg/dL) and creatinine (1.45 mg/dL), elevated testosterone (210 ng/dL; normal: 12-72 ng/dL), raised DHEA-S (235 μg/dL), hyperlipidemia, normal TSH (1.09 IU/mL), LH, FSH and estradiol. Abdominal ultrasound scan and uterine echotexture were normal and Pap smear was negative. CT scan brain showed normal pituitary gland. MRI brain and internal auditory canal showed a 2.1 x 1.1 x 1 x 1 cm right acoustic schwannoma in the internal auditory canal with extension into the cerebellopontine angle cistern with involvement of the right cochlea and the vestibule with no evidence of pituitary tumor or brain compression. Elevated testosterone settled after the trial of Leuprolide. Diagnosis of hyperandrogenism was made and bilateral salpingo-oophorectomy was performed. Bilateral laparoscopic salpingo-oophorectomy revealed left stromal luteoma, bilateral stromal nodular hyperthecosis (see ), and right paratubular cysts. However, uterine cavity was normal in size, nontender and mobile. MRI adrenals without contrast were normal. Testosterone secreting ovarian tumour was suspected.
pmc-6304558-1	A 35-year-old gravida 6, para 5 mother who is 38-week pregnant from last normal menstrual period has presented to Tercha General Hospital (a rural hospital in Southern Ethiopia). The patient is referred from a health center 60 kms far from this hospital for suspected “big baby” in labor. The patient was an illiterate housewife. In terms of past obstetrics history, all previous deliveries occurred at home vaginally with live birth with no major complication. During the index pregnancy, she had antenatal care visits at a nearby health center without ultrasound examination. She reports that the current pregnancy is heavier than previous ones and associated with significant discomfort than her previous pregnancy experiences. Otherwise, she has no self or family history of twinning in the past. Examination shows a stable gravida with normal vital signs. Abdominal examination shows big for date uterus with two cephalic poles in the lower abdomen and positive fetal heartbeat. Standard ultrasound examination confirmed twin pregnancy with both in cephalic presentation and adequate amniotic fluid; single placenta with no visible dividing membrane; fetal heartbeat is visible at two sites and is in a normal range. Upon pelvic examination, the cervix is 8cm dilated with left occiput-anterior position at a station 0. Fetal membrane is ruptured with clear liquor passing. With diagnosis of twin pregnancy (both cephalic presenting), in active phase of first stage of labor patient is admitted to labor ward and management of labor started in the standard way. In the next few hours labor progressed well and the first baby is crowning. Duty midwives are attending the delivery. Subsequently, with maternal effort the head and upper extremities of the first baby are delivered and the remaining part of the fetus is delivered by ‘gentle' traction by the midwives. But after delivery of the whole body, baby 1 remained ‘attached' to the mothers' perineum, though the baby is crying vigorously (). The midwives started to shout for help and senior obstetrician arrived. On reevaluation, we noticed the same and we found that the anterior abdomen of baby 1 from xiphisternum to the site of umbilical cord insertion is continuous into the uterine cavity. This led to sudden and unexpected consideration of the possibility of conjoined twins. Bedside ultrasound showed alive remaining fetus with fetal heart rate of 76 and in a transverse lie with the head in the right iliac fossa and fetal dorsum anterior. Initial attempt to access the extremities and aid delivery of the remaining fetus vaginally is not possible due to failure to reach the extremities for intrauterine manipulation. Emergency laparotomy is decided. Emergency laparotomy under general anesthesia with midline subumbilical abdominal incision and lower uterine segment vertical hysterotomy is performed. We corrected the lie of the born baby such that it is parallel to that of the unborn baby; with deep vaginal examination along with the caudal end of the attachment and managed to manipulate the lower extremities of the intrauterine fetus to vagina and after grasping those with the right hand vaginally, we brought it to the perineum. Then there is careful manipulation to bring those extremities posterior to the born baby with a second assistant holding and manipulating the born baby away from the area of manipulation. Progressive delivery of the second baby of the conjoined pairs is affected by total breech extraction with minimal difficulty. Both newborns were depressed at completion of the procedure and recovered after aggressive resuscitation for 10 minutes (). Both are male and their combined weight is 5800 gm. Ultrasound examination of the twins shows shared liver with no other organs shared. Latter the second baby passed away after 1 hour of stay at the NICU. The second baby died after 20 hours of stay, during transportation to higher center for possible emergency separation. The mother was discharged to home on her sixth post-op day after counseling.
pmc-6304559-1	A 69-year-old patient was diagnosed with a rectal adenocarcinoma (G2) on biopsy after an endoscopic control examination in 2013. He was treated first with radio adjuvant chemotherapy and subsequently with surgery. This combination of treatments has led to a complete response: any residual areas of cancer and lymph node involvement were documented on the surgical piece (yPT1N0 A/I G2 Sec MANDARD). In 2018, during regular oncological follow-up, a subpleural pulmonary nodule in lower lobe of the left lung of about 15x10 mm was detected. Considering the patient's clinical history, his general conditions, and localization of the lesion, a surgical resection of the lung was performed. On the macroscopic exam of the sample, physicians observed a neoformation of 1.9x1.5x0.6 cm, which is whitish, solid, with irregular but well-defined margins, 0.6 cm away from the surgical suture and 0.1 cm from the visceral pleura. Histologic examination demonstrated an epitheliomorphic neoplasm with acinar differentiation (). The adenocarcinoma cells were positive for cytokeratin 20 (CK20) and scattered positivity for caudal type homeobox 2 (CDX2) was found. TTF-1 was also strongly and diffusely positive. The tumor cells were negative for CK7 and Napsin A. Retrospective review of his previous primary tumor tissue showed similar histologic findings with TTF-1 positivity. On the basis of the positivity for CK20 and CDX2 with negative CK7 and Napsin A and of the morphology of the lesion, the diagnosis was the following: metastasis from TTF1-positive primary colorectal adenocarcinoma.
pmc-6304564-1	Our patient was a 24-year-old G2P0010 woman of Mexican descent who was admitted in August of 2017 for induction of labor for IUFD at 36 weeks of gestation. She was diagnosed with NMO in 2016 after initially presenting with symptoms concerning for area postrema syndrome, followed by magnetic resonance imaging (MRI) showing a spinal cord lesion from C2-T1 and a positive aquaporin-4 (AQP4) autoantibody. She was treated with a brief course of corticosteroids and azathioprine. Her past medical history was remarkable for recurrent syncope requiring placement of a permanent pacemaker in 2012 with a hospital course complicated by deep venous thrombosis of the common femoral vein and inferior vena cava (IVC), for which she received an IVC filter. She also had one prior therapeutic abortion at 9 weeks of gestation. Her home medications included subcutaneous heparin 10,000 units twice daily initiated one week prior to hospitalization for prophylaxis of venous thromboembolism, oxcarbazepine for muscle spasms, and prenatal vitamin. Labs on the day of admission showed hemoglobin of 9.9 grams/deciliter, platelet count of 223,000/microliter, fibrinogen of 491 milligrams/deciliter, international normalized ratio of 0.9, and partial thromboplastin time of 24 seconds. Transthoracic echocardiogram revealed normal ventricular and valvular function with no masses or cardiac source of emboli. During preanesthesia evaluation, the patient reported occasional muscle spasms and positional double vision but denied weakness and neuropathy. Her airway, cardiovascular, and pulmonary examinations were normal. A neurological examination of cranial nerves, sensation, motor function, cerebellar function, and reflexes was unremarkable. The patient was educated on the risks and benefits of neuraxial anesthesia based on the available literature, including the remote possibility of exacerbation of neurological symptoms. She elected to first try intravenous opioids for pain control, including intravenous hydromorphone followed by patient-controlled analgesia with fentanyl. However, she had a protracted course of labor and eventually requested epidural analgesia on the third day. A coagulation profile was rechecked and found to be normal. A lumbar epidural catheter was placed at the L3-4 interspace. Following a negative test dose, 100 micrograms of fentanyl and 8 milliliters of 0.2% ropivacaine were loaded. Consistent with our institution's protocol, an epidural infusion was started using 0.15% ropivacaine and fentanyl 2.5 μg/ml at 8 ml/hour with patient-controlled boluses of 8 ml every 20 minutes with a maximum dose of 2 boluses per hour. On that same afternoon, the patient delivered a demised neonate, and the cause of death was determined to be an umbilical cord accident. The patient was evaluated postpartum and reported no exacerbation in her pre-existing neurological symptoms. She was contacted via telephone at 5 months and 8 months after discharge, and she reported no change in her symptoms.
pmc-6304573-1	A male patient, 54 years old, 170 cm, 80 kg, American Society of Anesthesiologist Physical Status (ASA-PS) graded 3, was planned for elective cataract surgery. Previous medical history of the patient revealed severe psychotic disorder and drug-resistant epilepsy, diagnosed by the age of 6. He also suffered from congenital bilateral nerve palsy and stinging, type II diabetes mellitus, and dyslipidemia. Smoking, alcohol abuse, or allergies were not reported. Patient's activity, estimated by metabolic equivalents (METS), could not be assessed. His current medication included Levetiracetam mg 1500 mg twice daily, Oxcarbazepine 400 mg twice daily, Clobazam 10 mg once daily, Ebastine 20 mg every other day, Pregabalin mg 150 mg three times daily, Risperidone 2 mg twice daily, Metformin 500 mg twice daily, Ezetimibe 10 mg once daily, Eicosapentaenoic acid 1000 mg once daily, and Omeprazole 20 mg once daily. Due to poor communication and cooperation, the ophthalmologist in charge decided to operate the patient under general anesthesia. During preoperative screening, clinical examination did not reveal pathological findings, ECG was reported without specific lesions, and chest X-ray was normal. Preoperative airway evaluation revealed prognostic factors of difficult airway: Mallampati classification grade III, thyromental distance (TMD) <6cm, median teeth distance <3cm, and moderate cervical spine mobility. Due to anticipated difficult intubation and based on the poor physical status, a sedation technique with dexmedetomidine was decided instead of general anesthesia. After standard monitoring and intravenous line establishment, the patient was prehydrated with 300 ml of Ringer's Lactate, followed by a single bolus of 50 mcg of Fentanyl as an adjuvant analgesic. Infusion of dexmedetomidine started at a loading dose of 1 mcg/kg for 10 minutes, followed by a maintenance dose of 0.4 mcg/kg/h. However, after 17 minutes of commencement of dexmedetomidine infusion and before surgery, the patient suddenly suffered bradycardia with hemodynamic collapse. Blood pressure was 75/45 mmHg and heart rate 40 bpm. Immediately 0.5 mg of atropine was administered and infusion of dexmedetomidine stopped at the same time. Seconds after, cardiac arrest with asystole occurred. Advanced life support and cardiopulmonary resuscitation was implemented according to the European Resuscitation Council algorithm. Return of spontaneous circulation (ROSC) occurred at about 4 minutes after 2 cycles of cardiopulmonary resuscitation. The operation was postponed. When the patient gained satisfactory neurological status of consciousness, he was transferred to the Coronary Unit for further intensive care. Few hours later he was transferred to the ward in good overall condition.
pmc-6304583-1	A 36-year-old nulliparous woman with past histories of both RA and recurrent pregnancy loss (repeated abortion), probably due to a high titer of anti-phospholipid IgM antibody, was referred to our tertiary center at 10 weeks of gestation. RA had been diagnosed at 31 years old, and etanercept at 25 mg/day, twice a week, was started. Within 1 month, the simplified disease activity index (SDAI) had improved from 18.1 to 2.6 (). SDAI was the sum of the number of tender joints, the number of swollen joints, patient global assessment of disease activity using a visual analogue scale (VAS), care provider global assessment of disease activity by VAS, and the level of C-reactive protein (CRP) (mg/dL). At 32 years old, she became pregnant, and etanercept was changed to prednisolone at 4 mg/day; however, intrauterine fetal death (IUFD) occurred at 9 weeks. Thereafter, prednisolone was changed to etanercept at 25 mg/day (). Since she desired to become pregnant at 35 years old, etanercept was discontinued before pregnancy; she soon became pregnant, but at 7 weeks, IUFD occurred again. Thereafter, etanercept at 25 mg/day, twice a week, was restarted with a decreased dose of prednisolone at 4 mg/day (). Because of repeated abortion and the discovery of a high titer of anti-cardiolipin IgM antibody (twice ≥80 U/mL with intervals of ≥3 months [reference range: <8 U/mL]), low-dose aspirin at 100 mg/day and heparin calcium subcutaneous injection at 10,000 units/day were started before pregnancy, with the discontinuation of etanercept. At 36 years old, she became pregnant for a third time. Because SDAI was increased to 6.8 at 16+5 weeks, etanercept at 25 mg/day, twice a week, was reinitiated. However, etanercept was discontinued at 28+5 weeks, because the British Society of Rheumatology (BSR) and British Health Professionals in Rheumatology (BHPR) guidelines on prescribing drugs in pregnancy and breastfeeding recommended the usage of etanercept until the end of the second trimester []. Then, prednisolone was increased from 4 to 5 mg/day from 28+5 weeks; however, prednisolone was decreased from 5 to 2.5 mg/day from 38+5 weeks, because the SDAI was decreased from 7.9 to 4.9. Taken together, the SDAI scores during pregnancy were slightly higher than those before the current pregnancy. Aspirin was stopped at 35+6 weeks, and heparin was stopped at 40+2 weeks. She transabdominally delivered a male infant weighing 3,344 g at 40+5 weeks due to arrest of labor following its induction. A tonic-clonic seizure abruptly occurred without either hypertension or proteinuria 5 days after delivery; her blood pressure at the first seizure was 113/78 mmHg, and that at the second seizure was 109/72 mmHg (). Severe headache preceded the convulsion and continued after the seizure for almost 7 days. After the seizure, her consciousness was mildly disturbed (Japan Coma Scale I-3). There were no visual changes, and no hemiplegia. Computed tomography (CT) disclosed intraparenchymal hemorrhage with 2 cm diameter in the right frontal lobe () and a fluid-attenuated inversion recovery (FLARE) image obtained by magnetic resonance imaging (MRI) disclosed subarachnoid hemorrhage at the right Sylvian fissure (). MRI also revealed PRES in the bilateral frontal, temporal, and posterior lobes (Figures –). Laboratory data revealed that she was not complicated by either thrombocytopenia or disseminated intravascular coagulation. Levetiracetam at 1,000 mg/day, carbazochrome sodium sulfonate hydrate at 100 mg/day, and tranexamic acid at 1,000 mg/day were prescribed. Seizure recurred 2 days after the first one; however, cerebral images on CT did not change compared with those 2 days before the seizure (). MRI findings were ameliorated 1 month after the seizure (Figures –). We did not formally evaluate SDAI around the time of seizure occurrence; however, in retrospect, the patient reported that the patient global assessment of disease activity by VAS around the seizures was milder than in the term pregnancy period. Etanercept at 25 mg/day, twice a week, was restarted 42 days after delivery; and prednisolone was changed from 2.5 to 1.0 mg/day 133 days after delivery (). SDAI 3 months after delivery had markedly improved to 0.88.
pmc-6304601-1	A 41-year-old woman, gravida 2, para 1, was diagnosed with esophageal cancer relapse at 16 weeks of gestation. At the age of 40, before this spontaneous conception, she underwent preoperative chemotherapy, minimally invasive esophagectomy, and postoperative chemotherapy for esophageal squamous cell cancer, cStageII, pStageIV. Since the postoperative chemotherapy, she had been amenorrhoeic. Ten months after the operation, contrast enhanced computed tomography (CT) of the neck, chest, and abdominal to pelvis region was performed to investigate recurrence or metastasis, and it showed a pregnant uterus. She visited our obstetric clinic and was confirmed to be at 8 weeks of gestation. Because the estimated fetal exposure dose of the CT examination was less than 8 mGy, she wished to continue the pregnancy. At 16 weeks of gestation, the scheduled gastrointestinal endoscopy and biopsy revealed relapse of esophageal cancer in the residual esophagus (). The fluorine-18 fluorodeoxyglucose (18F-FDG) uptake of the local recurrence in the residual esophagus was elevated according to positron emission tomography (PET)/CT, and no metastatic lesion was detected. A multidisciplinary treatment team consisting of medical oncologists, radiation oncologists, surgeons, and obstetricians recommended that the patient terminate the pregnancy and receive CRT, which was the standard treatment for localized recurrent disease [, ]. However, the patient and her husband strongly desired to continue the pregnancy. To examine the safety and feasibility of radiotherapy for this patient, the fetal dose was estimated by a simulation study before CRT. We created the irradiation plan for the patient () and delivered doses to the phantom (). According to the radiation dosage measured by five dosimeters, which ranged from 0.052 to 0.176 mGy in one irradiation fraction (), the fetal dose was estimated as 1.56 to 5.28 mGy, even after 60 Gy in 30 fractions of radiotherapy. The anticancer drugs, which would be administered together with the radiation, were cisplatin (CDDP) and 5-fluorouracil (5-FU). Taking these results, we concluded that CRT during pregnancy in this case would be acceptable and, after receiving written informed consent, started the treatment at 19 weeks of gestation. The CRT consisted of 50.4 Gy in 28 fractions of radiation and four courses of chemotherapy (CDDP 60 mg/m2 on day 1, 5-FU 750 mg/m2 on days 1 to 4). shows the course of treatment over time. As supportive therapy, palonosetron and dexamethasone were administered. To assess the actual fetal dose of radiotherapy, we put dosimeters on the patient's abdomen at every irradiation session. Dosimeters showed that the estimated fetal dose ranged from 0.08 to 0.34 mGy in one irradiation fraction. Consequently, the multidisciplinary team confirmed the safety and feasibility of radiotherapy for this pregnant patient and fetus and completed the planned radiotherapy. After chemoradiotherapy, at 27 weeks of gestation, the recurrent lesion was decreased in size. Furthermore, gastrointestinal endoscopy at 31 weeks did not detect the recurrent lesion after the third course of chemotherapy. During this treatment, the myelosuppression was mild; grade 2 anemia, grade 1 neutrophil count decreased, and grade 1 platelet count decreased, according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The patient had also pharyngitis, anorexia, and vomiting. Regarding body habitus, her height was 162 cm, and her weight was 51 kg before the esophagectomy. Then she had lost 6 kg and her body mass index was 17.5 by the time she got pregnant. Her weight gain was only 3.9 kg during pregnancy because of impaired oral intake due to gastric tube reconstruction as well as adverse effect of CRT such as anorexia. The fetal estimated body weight fluctuated between the 10th and 20th percentile. Fetal well-being was monitored using ultrasound and nonstress fetal heart rate testing, and no abnormal findings were detected. At 38 weeks and 3 days of gestation, she underwent cesarean section (due to previous cesarean section) and gave birth to a female baby weighing 2,480 g. Apgar scores were 7 at 1 minute and 8 at 5 minutes, and the pH of umbilical artery blood was 7.327. The baby did not have any congenital anomalies, and the clinical course was uneventful. Twelve months have passed since the cesarean section, the patient has been free of disease, and the growth of the infant has been satisfactory.
pmc-6304607-1	A 36-year-old male patient presented with painless enlargement of his right scrotum of few weeks duration. History did not reveal any trauma or previous infections. Physical exam showed diffuse right scrotal nontender and firm mass with no palpable inguinal lymph nodes. Ultrasonography showed isoechogenic solid mass of 42x28.7 mm with two calcified foci at the apex posteriorly, the largest measuring 6.7x7.6 mm. Patient underwent right radical orchiectomy. Chest abdomen pelvis Computed Tomography (CT) scan was negative for metastasis. Patient has been followed up for 7 years and did not develop any recurrence on his yearly follow-up CT scan and urinary 5-HIAA. Histopathologic study showed, macroscopically, parenchyma of the testis partially occupied by a solid, well circumscribed, nonencapsulated mass measuring 5x4x3.5cm with a homogenous tan gray to “creamy” color. Grossly visible areas of hemorrhage and necrosis were absent. Within the center of the mass, there was a 0.4 cm calcified nodule. Tumor is grossly separated from the tunica albuginea and from testicular hilum by a grossly unremarkable, light brown, spongy soft testicular parenchyma. Microscopically, the neoplasm is composed of cohesive, uniform, cuboidal cells with minimal cytoplasm, arranged in nests and cribriform structures of variable size and shape, separated by moderate amount of fibrotic dense stroma (). At the periphery of the nodule, cord-like and trabecular growth patterns are noticed. Confluent as well as individual cell necrosis is absent. Neoplastic cells exhibit a uniform, round nuclei with regular contour and a granular chromatin. Prominent nucleoli are absent. Cytoplasm is pale, mild, and inconspicuous. Nuclear grooves are absent. Mitotic figures are absent to extremely rare (2 per 10 HPF) (). Tumor cells stained positive with cytokeratin (clones AE1/AE3), synaptophysin (), chromogranin A (), EMA, and CDX-2 () but negative for CD99, TTF-1, CK7, CK20, and CEA.
pmc-6304620-1	A 63-year-old woman with no significant medical history was referred to our hospital for further investigation of elevated liver enzyme levels and thrombocytopenia. The patient had a few days' history of general malaise and purpura of her legs. She had no fever or any abdominal complaints. She had a history of alcohol intake of about 40 g/day and no constant drug use. Her vital signs were stable and physical findings were normal except for jaundice and purpura of her legs. The laboratory findings were as follows: total bilirubin, 8.8 mg/dL; aspartate aminotransferase (AST), 1,767 U/L; alanine aminotransferase (ALT), 1,845 U/L; γ-glutamyl transpeptidase, 2,229 U/L; alkaline phosphatase (ALP), 845 U/L; immunoglobulin G (IgG), 2,042 mg/dl; anti-nuclear antibody (ANA) titer, positive at 80-fold dilution; platelet count, 22,000/μL; platelet-associated IgG (PAIgG), 208 ng/10∧7 cells. Serologic markers for hepatitis A, B, C, and E viruses, and Epstein-Barr virus, cytomegalovirus, varicella zoster virus, and herpes simplex virus were all negative, and anti-Helicobacter pylori (H. pylori) IgG was positive (). Abdominal ultrasonography and enhanced computed tomography revealed no significant biliary tract disease that could have led to liver damage. According to the criteria of the International Autoimmune Hepatitis Scoring System, the patient's pretreatment clinical score without histology was 13 (female: +2; ALP/ALT ratio: +2; IgG level: +1; ANA titer: +2, antimitochondrial antibody: 0; viral markers: +3; drugs: +1; alcohol: 0; immune disease: +2), indicating probable AIH. Her severe thrombocytopenia was considered to be due to concomitant ITP because of her clinical and laboratory findings. Liver biopsy via the transjugular route (TJLB) was selected to confirm the diagnosis of AIH to avoid the risk of hemorrhage after percutaneous liver biopsy (PLB) in a patient with severe thrombocytopenia. The right internal jugular vein was punctured after administering local anesthesia, and a 5-Fr catheter cannulated into the right hepatic vein (RHV) over the guide wire. A venogram was performed to confirm the position of the catheter in the RHV (). The catheter was then exchanged for a transjugular liver access and biopsy set catheter (Cook Medical, Bloomington, IN). Five liver biopsy specimens were obtained. All steps were performed using X-ray fluoroscopy to confirm the location of the guide wire or catheter. A postbiopsy venogram revealed no complications, including intraperitoneal hemorrhage (). Manual compression of the access site on her neck was applied from catheter removal until hemostasis was achieved. The histological findings of liver biopsy showed interface hepatitis and moderate to severe inflammatory infiltrates including lymphocytes and plasma cells. Moderate fibrosis in the portal area and partial destruction of the hepatic lobules with partial piecemeal necrosis was also observed (Figures , , , and ). All these pathological findings were compatible with the diagnosis of AIH, and the postbiopsy score was 17, thereby confirming the diagnosis of AIH. Bone marrow aspiration revealed a normal nucleated cell count and a slight increase in megakaryocytes, suggestive of ITP (). She received an intravenous glycyrrhizin-containing herbal medicine, Stronger Neo-Minophagen C (SNMC; Minophagen Pharmaceutical, Tokyo, Japan) at 60 ml/day before TJLB, and prednisolone (PSL) at 55 mg/day (0.8 mg/kg/day) after the histological diagnosis of AIH. After PSL administration, the patient demonstrated a good response with restored liver enzyme levels and platelet counts (). PSL was tapered to 5 mg/day as a maintenance dose. The patient recovered uneventfully except for a hyperglycemic event requiring insulin treatment.
pmc-6304633-1	A 37-year-old female with a past medical history significant for type I diabetes mellitus for > 20 years, Addison disease, and systemic lupus erythematosus presented to the emergency department with increasing abdominal pain over a six-day period. She also described poor oral intake and several episodes of nausea with blood-tinged emesis. She was treated 6 weeks earlier for Clostridium difficile colitis and completed a full course of antibiotics with resolution of symptoms; however over a week prior to the current admission her diarrhea had recurred. She denied any history of tobacco or alcohol use but did describe daily marijuana use. She was taking hydrocortisone 20 milligrams (mg) twice daily (bid) for Addison disease, insulin lispro 5 units (u) with meals, and insulin glargine 10 u at night. On admission her vital signs were temperature 97.1° F, blood pressure 130/102 mmHg, heart rate 140 beats/minute, and respiratory rate 26 breaths/minute. Her physical exam was only significant for abdominal guarding. The remainder of the physical exam was unremarkable. Metabolic panel demonstrated a blood glucose of 763 mg/dL, CO2 of 8 mmol/L, and β-hydroxybutyrate of 15.3 mmol/L with an anion gap of 36 mmol/L. Arterial blood gas (ABG) was significant for a metabolic acidosis with a pH of 7.11 and HCO3 of 4.1 mmol/L. Additional laboratory values were significant for urinary ketones of 80 mg/dL, urine glucose of ≥ 500 mg/dL, and a hemoglobin A1C of 15.3%. The findings were consistent with diabetic ketoacidosis (DKA) and she was started on an insulin drip with aggressive intravenous fluid resuscitation. Due to her significant abdominal pain, a computed tomography (CT) of the abdomen and pelvis was done which revealed extensive low-attenuation surrounding the distal esophagus with esophageal wall thickening (). Gastroenterology was consulted in regard to the abnormal CT findings and the decision was made to perform an esophagogastroduodenoscopy (EGD) which revealed severe, diffuse esophageal ulcerations and necrosis (). A diagnosis of necrotizing esophagitis was made. The patient was started on a pantoprazole drip, oral sucralfate, and a clear liquid diet. Her stool workup was negative and the diarrhea responded to antimotility agents. The anion gap closed, and blood sugars normalized. She improved clinically but left the hospital against medical advice on hospital day 3 before complete resolution of her symptoms.
pmc-6304635-1	An eighteen-year-old male presented to the Emergency Department with fever and severe chest pain. His symptoms developed five days earlier when he woke up with a sore throat. He was seen by his pediatrician who performed a negative Rapid Group-A Streptococcus swab. Over the following three days, he developed nausea, vomiting, intermittent fevers, sweats, and chills. He went back to his pediatrician who this time started him empirically on oseltamivir phosphate for presumed influenza. His symptoms of sore throat and chills improved the night prior to admission, but then he developed severe suprasternal chest discomfort and pleuritic chest pain. He had never used alcohol or illicit drugs. In the Emergency Department, the patient was initially afebrile, but shortly after his initial evaluation he developed a fever of 103 degrees Fahrenheit. He was hypotensive with a blood pressure of 88/46 mmHg and a heart rate of 127 beats per minute. His initial saturation was 99% on room air. On examination, he was noted to be drowsy but oriented to person, place, and time. He had moist mucous membranes and no throat exudates. He had no carotid bruits or cervical or axillary lymphadenopathy. His pulmonary auscultation was normal, and his heart exam had no murmurs. He had no cyanosis or mottling of skin. Labs were notable for white count of 17 thousand per mL with 28% bands, total bilirubin of 2.4 mg/dL, platelet count of 50 thousand per mL, lactic acid of 3.1 mg/dL, and a negative troponin. A plain chest X-ray had no acute abnormalities, and a noncontrast CT scan of his chest demonstrated bibasilar patchy infiltrates (). After blood cultures were drawn and with a presumed diagnosis of bilateral community acquired pneumonia, Levofloxacin, and Clindamycin were initiated. Because of hypotension, bandemia, and lactic acidosis, he was admitted to the Intensive Care Unit for further monitoring. Within 12 hours, he had a rapid and sharp clinical decline with worsening and severe hypoxemia and marked progression of his bilateral pulmonary infiltrates readily evidenced on CXR. He required mechanical ventilation and was diagnosed with Acute Respiratory Distress Syndrome (ARDS). Pressure control ventilation with positive end-expiratory pressure (PEEP) up to 20 cm H20 and paralytics were needed to maintain adequate oxygenation and saturation. He was subsequently transferred to a tertiary care center for further management and possible Extracorporeal Membrane Oxygenation (ECMO) which in the end he did not require. Two days later, patient had two blood cultures which grew Fusobacterium necrophorum.
pmc-6304639-1	A 48-year-old male with B-cell acute lymphoblastic leukemia in partial remission receiving inpatient chemotherapy experienced left eye progressive vision loss, tearing, and redness for three days. On ophthalmological consultation, the left eye had a visual acuity of counting fingers at 1 foot with an afferent pupillary defect. Examination revealed 4+ cell and flare in the anterior chamber with 2mm hypopyon and dense vitreous haze in the posterior pole. Given the concern for endogenous endophthalmitis in an immunocompromised patient, a diagnostic pars plana vitrectomy was performed and a vitreous biopsy was obtained. Intravitreal antibiotics and antifungals were injected through the trocars. Intraoperatively, a pink nonpigmented 2 x 3 x 2mm (W x L x H) elevation was noted on the mid-peripheral superonasal retina. Given this lesion and the patient's declining mental status, imaging and cerebrospinal fluid sampling were performed. MRI brain illustrated rim-enhancing lesions with diffusion restriction in the right peritrigonal and left corona radiata () while orbital sections showed circumferential smooth enhancement in the left globe and optic nerve sheath (Figures and ). Cerebrospinal fluid removed from the right frontal ventricular reservoir through which the patient was receiving intrathecal chemotherapy showed no bacterial or fungal growth. Despite systemic use of antibiotics and antifungal medications, the patient's mental status over the next several days declined to the point where he could no longer follow commands. Repeat MRI brain 10 days later showed increasing sizes of the rim-enhancing lesions. Vision became “no light perception (NLP),” inferior retinal detachment was noted on exam, and the vitreous biopsy had still not grown any organisms. Both culture-negative endophthalmitis and uveitis masquerade syndromes such as intraocular malignancy still remained real life-threatening possibilities. Given the systemic risk of a bacteremia or malignancy, the ophthalmology team decided to proceed with a transvitreal retinochoroidal biopsy []. Septate filamentous fungi with acute angle branching characteristic of Aspergillus fumigatus were noted on retinochoroidal biopsy (). The patient was subsequently started on systemic voriconazole and amphotericin B. Two weeks later, culture from the initial vitrectomy demonstrated Aspergillus fumigatus (). Pathology from the brain tissue that was biopsied by neurosurgery demonstrated organisms morphologically consistent with Aspergillus as well (). Flow cytometry to rule out intraocular malignancy demonstrated an immunophenotypically normal cell population and cytology done on the vitreous biopsy did not show malignant cells. The patient was ultimately discharged from the hospital to a rehabilitation facility where he was informed that he would likely need enucleation of the left eye as an outpatient.
pmc-6304640-1	In January 2013, a 50-year-old Caucasian male patient underwent, without an adjunctive brachytherapy, endoresection of anteriorly located spindle cell choroidal melanoma. In December 2014, multiple pigmented scleral lesions were found on the same eye, with the outermost lesion located 5 mm away from the limbus. The second patient, 44-year-old Caucasian male, underwent the same procedure for the anteriorly located mixed cell choroidal melanoma, in July 2011. Six years later a massive recurrence of the tumour was infiltrating the anterior eye segment with extraocular limbal extension. Both patients underwent an extended enucleation with removal of almost all orbital tissues en bloc including the eye, anterior portion of the extraocular muscles, and long section of the optic nerve. Antiseptic douching of the eye with 10% povidone-iodine was performed preoperatively. Conjunctiva was opened at the fornices, so that the entire bulbar conjunctiva could have been removed with the eye en bloc, avoiding manipulation of the tumour-infiltrated areas. Dislocating the eye out, the extraocular muscles were cut as far posterior as possible. Optic nerve was severed approximately 10 mm from the eyeball. Silicone sphere of 22 mm (FCI Ophthalmics) was implanted deeply into the orbit through a glide made from the thumb of a sterile polythene glove []. During the same procedure, dermis fat graft, harvested from the left suprapubic area, was used to cover the implant []. The size of the graft was 30 mm in height and 35 mm in length with 20 mm of the fat thickness. Interrupted 6/0 absorbable sutures were used to fixate the graft to the residual conjunctiva at the fornices taking care of the fact that the conjunctiva overlaps the edge of the graft by two millimetres. At the end of the surgery, silicone conformer was inserted and kept for the entire time of the graft epithelization. Broad-spectrum topical antibiotic prophylaxis (tobramycin drops qid) was applied for seven postoperative days. Epithelisation of the dermis fat graft was completed in two months, leaving well-formed fornices with good fitting of the prosthesis (Figures and ). A small conjunctival granuloma appeared two months postoperatively in the first patient and was managed by simple surgical intervention. So far, the first patient has been followed for four years and the second for eight months, without experiencing any major complication [, ].
pmc-6304642-1	An 83-year-old white male presented with melena 3 to 4 times per day and occasional hematochezia over one week. He was known to have atrial fibrillation for which he was on warfarin at home. His INR was supratherapeutic (4.9) few weeks ago at his primary care physician's office. He was told to hold his warfarin for 2 days and then restart at a lower dose. Recheck of INR was 2.9 after few days. But he started having melena. His other medical problems included significant cardiac history of coronary artery disease, status post coronary artery bypass graft x 3 in 1980, coronary angioplasty and stent placement in 2004, hypertension, hyperlipidemia, and prostate cancer, status post prostatectomy. He was a social drinker and a smoker. He was active in his daily life. His family history was not significant. His home medications were warfarin, sotalol, valsartan, atorvastatin, ezetimibe, isosorbide mononitrate, folic acid, cholecalciferol, ascorbic acid, and selenium. Examination showed pulse 62/minute, blood pressure 118/67 mm Hg, pale conjunctiva, and abdomen that was soft, nontender, and with no palpable mass. Rectal examination revealed melanotic occult blood positive stool. The remainder of the examination was unremarkable. Laboratory studies showed hemoglobin 7 gm/dl, white cell count 11,400/cmm, and platelet count 156,000/cmm. Patient was started on intravenous pantoprazole. EGD showed mild bulbar duodenitis and a small superficial ulcer and multiple nonbleeding angioectasias in the gastric antrum. The angioectasias were ablated by argon plasma coagulation. Antral biopsy was negative for H. pylori infection. Colonoscopy showed moderate sigmoid diverticulosis, 1.5 cm pedunculated sigmoid colon polyp which was snared and retrieved. There was a subcentimeter nodular area with abnormal vascular pattern in the transverse colon (). Polyp histology came back as tubular adenoma and the nodular area showed marked small lymphocytic infiltrate predominantly comprised of B-cells with lymphoepithelial lesion (). The B cells were negative for CD5, CD10, BCL-1, and BCL-6. CD 21 highlighted expanded and disrupted follicular dendritic meshwork. Concurrent molecular studies detected a clonal immunoglobulin heavy chain (IGH) rearrangement. These findings were consistent with extranodal marginal zone lymphoma or colonic MALToma. PET/CT scan showed a 3.9 × 3.0 cm ground glass opacity in the upper lobe of right lung (Figures and ), which had increased in size since the prior CT done 8 years ago when it was measured 1.9 × 1.1 cm (). The lesion was suggestive of low-grade adenocarcinoma of the lung as it did not have any hypermetabolic activity. There was no focal hypermetabolic activity in the liver or abdomen. The patient refused to have any biopsy of the lung mass. He was seen by an oncologist for further management. He did not want to have any surgery or chemotherapy for his lung cancer. The patient was recommended to have another colonoscopy done in 6 months' time for follow-up of his colonic MALToma.
pmc-6304645-1	Case 1. A 64-year-old male with a medical history significant for hyperlipidemia, hypertension, DM type 2, CKD, and prostate cancer treated with radiotherapy presented to the urology service for 3-piece IPP placement due to erectile dysfunction refractory to medical management. Preoperative anesthesia assessment 14 days prior revealed a serum creatinine of 1.41 mg/dL and an estimated glomerular filtration rate (eGFR) of 65.08 mL/min/1.73 m2. On the day of surgery, the patient received IV gentamicin 160 mg (2.46 mg/kg ideal body weight) and IV vancomycin 1000 mg (8.96 mg/kg) 11 minutes prior to first incision. IPP (3-piece Coloplast Titan® Touch, Minneapolis MN, USA) placement was performed without complication following intraoperative placement of a Foley catheter. A total of 1,807 mL IV normal saline was administered intraoperatively and systolic blood pressure remained above 90 mmHg throughout the procedure, of which the total operative duration was 147 minutes. A Jackson-Pratt (JP) drain was placed in the right hemiscrotum, and the catheter was maintained. Postoperatively, the patient was restarted on his home medications. On the 1st postoperative day, the patient was afebrile without nausea or vomiting, and with adequate urine output. Drain outputs were minimal, prompting removal. Notably, the patient's serum creatinine was found to have risen to 2.92 mg/dL (eGFR 28.09 mL/min/1.73 m2). Repeat serum creatinine that afternoon showed a continued rise to 3.04 mg/dL (eGFR 26.82 mL/min/1.73 m2), consistent with a stage-2 AKI by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The nephrology service was consulted and recommended continuing IV hydration. On the 2nd postoperative day, urine output was again adequate, and serum creatinine was found to be stable at 3.02 mg/dL (eGFR 27.02 mL/min/1.73 m2). The patient was discharged and on postoperative follow-up 44 days later, his renal function was found to have largely improved to a serum creatinine of 1.68 mg/dL (eGFR 53.17 mL/min/1.73 m2).
pmc-6304645-2	Case 2. A 65-year-old male with a history of hypertension, DM type 2, and refractory erectile dysfunction underwent IPP implant. During preoperative anesthesia assessment 21 days prior, he demonstrated baseline renal function with a serum creatinine of 1.02 mg/dL and eGFR of 94.27 mL/min/1.73 m2. Intraoperatively, he received IV gentamicin 300 mg (3.73 mg/kg ideal body weight) and IV vancomycin 1000 mg (8.73 mg/kg) within 20 minutes prior to first incision. The IPP (3-piece Coloplast Titan® Touch, Minneapolis MN, USA) was inserted without complication during the total operative duration of 153 minutes. The patient received 1,800 mL IV normal saline intraoperatively. On the 1st postoperative day, the patient remained clinically well and his Foley catheter and JP drains were removed. However, his serum creatinine was discovered to increase to 2.67 mg/dL (eGFR 31.05 mL/min/1.73 m2), consistent with a stage-2 AKI. Repeat serum creatinine that evening demonstrated a continued rise to 3.92 mg/dL (eGFR 19.94 31.05 mL/min/1.73 m2), a stage-3 AKI. On the 2nd postoperative day, the patient's serum creatinine rose further to 5.95 mg/dL (eGFR 12.32 mL/min/1.73 m2) at which point he became transiently oliguric. The nephrology service was consulted and hemodialysis was initiated. By the 4th postoperative day, his serum creatinine increased to a peak of 7.11 mg/dL (eGFR 10.03 mL/min/1.73 m2). His urine output eventually began to improve and by the 7th postoperative day, his serum creatinine improved to 4.98 mg/dL (eGFR 15.12 mL/min/1.73 m2). He was then discharged with instructions to follow-up in nephrology clinic. At postoperative follow-up 19 days later, the patient's serum creatinine had continued trending down to 1.53 mg/dL (eGFR 59.04 mL/min/1.73 m2), and 6 months postoperatively the patient's renal function further improved to a serum creatinine 1.22 mg/dL (eGFR 76.43 mL/min/1.73 m2), notably still above his original baseline.
pmc-6304645-3	Case 3. A 65-year-old male with a medical history significant for obesity, hypertension, CKD, DM type-2, and erectile dysfunction managed with IPP placement 12 years prior presented for evaluation of his intermittently malfunctioning device. The decision was made to proceed with device revision. Preoperative serum creatinine was found to be 1.55 mg/dL (eGFR of 58.16 mL/min/1.73 m2) 14 days prior to surgery. He received IV gentamicin 230 mg (3.07 mg/kg ideal body weight) and IV vancomycin 2000 mg (17.12 mg/kg) within 30 minutes prior to first incision. The previous IPP (3-piece AMS 700™ Boston, Massachusetts, USA) device was successfully explanted (with the exception of the reservoir) and replaced (3-piece Coloplast Titan® One Touch Release, Minneapolis MN, USA) without complication. A total of 1,000 mL IV normal saline and 500 mL IV 5% dextrose in water (D5W) was administered intraoperatively during the 147 min procedure. He began convalescing appropriately postoperatively and his drains were removed on day 1; however, he developed a stage-1 AKI as demonstrated by an increase of serum creatinine to 2.09 mg/dL (eGFR 41.19 mL/min/1.73 m2). On the 2nd postoperative day, the serum creatinine was found to have stabilized at 1.98 mg/dL (eGFR 43.85 mL/min/1.73 m2) and he was subsequently discharged. On postoperative follow-up 24 days later, the patient's renal function normalized to a serum creatinine of 1.54 mg/dL (eGFR 58.42 mL/min/1.73 m2).
pmc-6304646-1	A 33-year-old female patient consulted due to a two-week history of disorientation and somnolence which progressed to stupor, requiring invasive mechanical ventilation. The patient had a history of a Cesarean section four months prior to her admission to the emergency room, without complications during pregnancy or delivery, and no known medical, pharmacological, allergic, or family history. The physical exam was remarkable for the presence of jaundice and hepatomegaly, without clinical signs suggesting cirrhosis. The admission laboratory tests registered an altered liver profile () with elevated ammonia (595.7 umol/L). Therefore, an abdominal tomography was performed, reporting a focal liver lesion which was interpreted to be a hepatic adenoma. Abdominal magnetic resonance imaging was then carried out () which showed results compatible with fibrolamellar hepatocarcinoma, with no signs of cirrhosis or portal hypertension. In light of her neurological deterioration, a simple head tomography was performed which showed unspecific periventricular lesions. A lumbar puncture ruled out infectious involvement, and telemetry reported moderate encephalopathy without seizure activity. Operating under the diagnostic impression of hyperammonemic encephalopathy, urea metabolism disorders were studied, including urinary orotic acid levels, serum amino acids, and serum citrulline levels, all of which were normal (). Given the lack of an etiology of the hyperammonemic encephalopathy and findings suggestive of fibrolamellar hepatocellular carcinoma, a liver biopsy was performed which confirmed the diagnosis through immunohistochemistry () which reports diffuse and intense expression for cytokeratin 7Y CD68, with marked sinusoidal capillarization with CD34 and expression for CD68 there is weak but diffuse expression for glutamine synthetase, and glypican 3 and amyloid A are negative. The expression for B-catenin is membrane, without aberrant expression. The cell proliferation index determined with KI 67 is 5%. This morphological and phenotypic pattern favors a fibrolamellar variant hepatocellular carcinoma. Extension studies ruled out metastatic bone or chest involvement, and neoplastic lesions elsewhere. The hyperammonemic encephalopathy was associated with intrahepatic shunts secondary to the tumor. Management was begun with continuous veno-venous hemofiltration and ammonium benzoate treatment, which led to a progressive improvement in her state of consciousness. On surgical evaluation, resection of the lesion was contraindicated due to extrinsic vascular and bile duct compression. Therefore, cadaveric donor liver transplantation was performed, with no postoperative complications. The explant study evidences the presence of a single lesion confined to the liver corresponding to the FHCC, with borders of hepatic hilum and suprahepatic section free of tumor, not identifying vascular invasion, perineural, lymphatic, nor lymph node, so resection of regional lymph nodes was not necessary. The patient is currently being followed by the hepatology department, with no signs of neurological alterations or tumor relapse, and a normalized liver profile ().
pmc-6304652-1	We describe a case of a 55-year-old man who presented with six months of progressive cognitive decline, multiple recent falls of unknown etiology, and behavioral changes. The falls had resulted in widespread bruising, which the patient attributed to “arthritis”. His behavioral changes notably included a heightened religious preoccupation, in which he had joined four new churches and would spend hours every day walking along highways between these institutions as well as a synagogue. He had registered several of the pastors as his healthcare proxies. He would spend further hours of his day documenting his thoughts and reading philosophical writings. In addition, he had become convinced that his parents were “out to get me”. On initial presentation, the patient's delusions were limited to paranoia and he denied perceptual disturbances. He was irritable and impulsive, attempting to elope on several occasions from the emergency department. His thought process had become “sticky”, in which he would adhere to or ruminate over specific ideas and give long-winded circumstantial responses to simple questions. He became convinced that he was in the hospital for his arthritis and that the hospital staff was intentionally trying to manipulate his brain. Upon admission, he called several pastors to visit and quickly amassed a collection of religious and philosophical books as well as notebooks, in which he would document his thoughts and the behaviors of staff on the unit. Interestingly, from the second day on the inpatient unit, he exhibited intermittent “absence-like” seizures, consisting of an abrupt onset of staring, accompanied by abnormal stereotypic movements of the left arm and facial contraction. During these episodes, the left side of the patient's face would spasm—mouth being pulled upwards and backwards and left eye blepharospasm—with a concurrent flexion and raising of the left arm and immediate resolution to prior position within five seconds. These events occurred periodically and irregularly several times each day and were associated with transient anterograde amnesia. The patient had a complete lack of insight into these occurrences to the point of carrying a phrase to completion despite experiencing an attack partway through the sentence. Other than superficial bruising, physical examination was unremarkable. Vital signs were stable other than a fluctuant pulse rate that would periodically rise to sinus tachycardia in the 130's. Routine laboratory values were unexceptional, other than mild hyponatremia (Na = 131-133). Surface Video EEG was negative for epileptiform activity despite capturing several of the clinical episodes noted above. Brain MRI without contrast showed bilateral T2-hyperintensities (R>L) in the parahippocampal gyri without volume loss in the temporal mesial structures (see ). To target his mood symptoms and seizure activity, he was initially started on valproic acid and titrated to a therapeutic dose over the course of one week; however, his seizure activity was refractory and increased in frequency with worsening of mental status and memory deficits. His treatment was thus augmented with risperidone and titrated to 2 mg twice daily over the ensuing two weeks, which resulted in a modest reduction in paranoia and ruminations; however, his cognition continued to decline, with a progression of negative symptoms to near catatonia and his seizures persisted. CSF obtained from a lumbar puncture was sent to an outside laboratory for serology on an autoimmune panel and confirmed the presence of antibodies towards the LGI1 portion of the VGKC complex and no other autoimmune antibody including anti-CASPR2, another anti-VGKC antibody. He was transferred to the neurology service and diagnosed with anti-LGI1 ALE. He was promptly treated with intravenous methylprednisolone 1 g daily and intravenous immune globulin 400 mg/kg/day, with instructions to continue on oral prednisone, as per recommendations from the literature [–], leading to improvement of his disorganization and psychiatric symptoms and to a substantial decrease in his dystonic movements within days but a slower resolution of his cognitive impairment over the following month.
pmc-6304698-1	A 48-year-old male presented with a chief complaint of bilateral hip pain, more prominent on the right side. The pain was described as intermittent, but significantly progressing in the most recent year, with daily occurrence. The pain was constant and worsened when walking, during prolonged periods of sitting, with sitting to standing, and with physical exercises including running. The patient noted a severe limitation in mobility, experienced with simple activities such as putting on socks and shoes. Past medical, family, and social histories were unremarkable. Conservative management including anti-inflammatory medication, activity modification, icing, home exercising, stretching, and resting had not provided significant relief. Initial orthopaedic examination of the right hip revealed a range of motion of 0° to 90° of flexion with pain at end range, internal rotation (IR) in flexion 5°, external rotation (ER) in flexion 40°, abduction 40°, and adduction 10°. Anterior impingement test on the right side and Patrick’s test to the groin were both positive. On examination of the left hip, range of motion was 0° to 95°, IR in flexion 10°, ER in flexion 50°, abduction 50°, and adduction 10°. Anterior impingement testing on the left was positive. Abductor strength was 5/5 bilaterally. No deformities were identified, and neurological status was intact. Plain film radiographs revealed bilateral hip osteoarthritis with the presence of osteophytes, joint space narrowing, sclerosis, and cam-type femoroacetabular impingement (). Based on patient history, age, and examination findings, final diagnosis was bilateral hip osteoarthritis, right hip greater than the left. Treatment options for the right hip included cortisone injection, THA, or BHR. After discussing the risks and benefits of each procedure, the patient opted for right BHR due to his active lifestyle. Surgery was performed with the assistance of C-arm fluoroscopy and Intellijoint HIP® (Intellijoint Surgical Inc., Waterloo, ON, Canada; off-label use), a 3D mini-navigation tool currently approved for use in posterior, lateral, and direct anterior approaches for THA. While this device has received clearance from the FDA for use in primary and revision THA, it has not been evaluated for use in BHR. The posterior application of the navigation device was followed, which has been described in detail previously (). The patient was placed right side up in the lateral decubitus position and stabilized using a pegboard. The right hip and lower extremity were prepped and draped in usual sterile fashion, followed by a confirmed surgical time out. Two 5-mm stab incisions were made at the iliac crest to accommodate the pelvic screws, pelvic platform, and camera of the navigation system, at which point the horizontal and frontal planes of the patient were registered. A 12-cm posterolateral incision was made and the tensor fascia latae and gluteus maximus fascia were incised. The sciatic nerve was palpated and protected. The gluteus medius and minimus were also protected. Short external rotators and quadratus femoris tissue were incised, leaving a cuff to prevent medial femoral circumflex bleeding. Hemostasis was adequate throughout the entire procedure and the sciatic nerve was palpated and protected throughout the entire procedure. A femoral disc was placed on the lesser trochanter to accommodate the tracker of the navigation tool. Hip biomechanics were registered including baseline leg length. Subsequently, the posterior capsule was incised in a U-shaped capsulotomy. The hip was dislocated atraumatically. Circumferential release of the capsule was performed. With the assistance of C-arm fluoroscopy, a guide pin was placed at the centre of the femoral neck at an angle of approximately 138°. C-arm fluoroscopy and biplanar imaging demonstrated excellent positioning of the guide. The femoral head was prepared per usual fashion using barrel reamer, chamfer reamer, and spherical reamer to create a spherical femoral head. At this point, a femoral cup trial was placed. Excellent fixation was noted without any notching or impingement. Next, the femur was transitioned anteriorly using assistance and blunt retractors. The acetabulum was visualized circumferentially with difficulty due to the stiffness of the hip. The labrum and pulvinar were excised and medial wall was visualized. Sequential reaming was performed. Medialization was excellent without a breach, with great cortical cancellous bleeding bed, and with sequential reamers in 1- and 2-mm increments. Next, a 58-mm acetabular component was impacted in place using the navigation system to confirm excellent angulation at 44° inclination and 20° anteversion, noting excellent seating, alignment, and stability. C-arm fluoroscopy demonstrated excellent positioning of the acetabular component with grade medialization and adequate seating. Next, Simplex cement was mixed per usual fashion and placed in the femoral head which was then impacted into place. Excellent fixation was noted. Cement was allowed to harden, with excess cement removed. Hip was relocated atraumatically. Hip range of motion and stability tested excellent. The navigation system was utilized to confirm baseline leg length restoration, followed by the removal of all navigation-related materials. Copious lavage was performed followed by closure. Skin glue was applied. Aquacel dressing was placed. Patient was awakened, extubated, and brought back to the recovery room in stable condition with no complications noted. Post-operatively, the patient was doing extremely well with no pain and full return of mobility. At his 12-week follow-up visit, the patient stated he was back to most of his physical activities and was happy with his progress. An antero-posterior (AP) pelvis x-ray of the right hip showed BHR that was well aligned with no evidence of loosening and no femoral neck fracture ().
pmc-6304699-1	Our patient was an 83-year-old male with past medical history of hypertension, hyperlipidemia, atrial fibrillation, cerebrovascular accident, and end-stage renal disease. He was on scheduled hemodialysis treatment through a catheter on his right chest. He was brought to the emergency department for fever and rigors of 1-day duration, with a recorded body temperature of 101.8°F. There was no cough, chest pain, shortness of breath, abdominal pain, diarrhea, vomiting, headache, altered mental status, and pain or burning on urination. Physical examination and the initial investigations failed to elucidate any obvious focus of infection. The patient was admitted for possible sepsis associated with infected dialysis catheter, and treated empirically with intravenous cefepime 1 g every 24 hours, intravenous vancomycin 15 mg/kg body weight every 24 hours, and intravenous metronidazole 500 mg every 8 hours. The dose of vancomycin was altered as needed to maintain the vancomycin trough level between 15 µg/mL and 20 µg/mL. Two sets of initial blood culture and subsequent dialysis catheter tip culture grew Staphylococcus aureus resistant to methicillin but sensitive to vancomycin, daptomycin, rifampin, and tetracycline, while a transthoracic echocardiography revealed right atrium mass, suggestive of endocarditis. The patient was therefore continued only on intravenous vancomycin for MRSA endocarditis. On the 11th day of admission, the patient developed palpable purpura on his both lower limbs (). He denied any pain or itching. While the erythrocyte sedimentation rate was elevated to 45 mm/h (normal = 0-30 mm/h), rest of his immunological workup including c-ANCA, p-ANCA, and atypical ANCA were negative, and C3, C4 levels were normal. Skin biopsy was done, which revealed severe leukocytoclastic necrotizing small cell vasculitis consistent with hypersensitivity vasculitis related to drug therapy (). So his vancomycin was switched to daptomycin. The purpura started to resolve within 3 days of discontinuing vancomycin. Both his vasculitis and initial clinical condition continued to resolve during the rest of his hospitalization, and he was successfully discharged after 22 days of hospital stay.
pmc-6304758-1	A 3-year-old white boy who had undergone distal hypospadias surgery 1.5 years ago presented with a slowly growing mass on the left side of his penis and dehiscence of the urethra. His medical, social, environmental, and family history were otherwise unremarkable. His developmental milestones and psychosocial status were compliant with his percentile. His parents were non-consanguineous. On admission, his temperature was 36.2 °C, pulse was 96 beats/minute, and blood pressure was 85/54 mmHg. A physical examination revealed the distal urethral dehiscence and the pattern of urine flow was abnormal. The mass which was located in the ventral aspect and distal part of his penis was painless and hard in texture. The dimensions of the mass were 2 × 2.5 cm (Fig. ). Bilateral testes were in his scrotum and normal sized according to the age. A neurological examination of the child was unremarkable. In laboratory analysis, total white blood cell (WBC) count was 6.9 103/mm3, hemoglobin was 12.4 g/dL, alanine aminotransferase (ALT) was 14 u/l, aspartate aminotransferase (AST) was 18 u/l, and creatinine was 0.6 mg/dl. Urine analysis showed normal amounts of red cells with no suspicion of urinary tract infection. For treatment, tubularized incised plate urethroplasty (TIPU) and accompanying cyst excision were performed. In histopathological examination of the mass, it was determined that the wall of the epidermoid cyst was composed of multilayered squamous epithelium which was keratinized toward the lumen (Fig. ). His post-operative course was uneventful and no urethral fistula occurred during 6-month follow-up. His urine flow was straight and the cosmetic outcome of the surgery was satisfactory.
pmc-6304823-1	A 25-year-old male patient, victim of torsional trauma in the right knee during a soccer match, was brought to the emergency department with a locked knee. At the time of the injury, the patient felt a pop and immediately after, he could not move his knee. Plain radiographs of the knee showed no signs of acute osteoarticular lesions. Subsequently, magnetic resonance imaging identified a bucket handle tear in the medial meniscus (). The patient was referred to the orthopedic trauma service for emergency surgical treatment. One week after the injury, the patient sought our service. Physical examination revealed the following findings: joint effusion, 30 degrees of flexion, and an inability to actively contract the quadriceps. In the prone position, an important contracture of the hamstring muscle group was observed when compared to the contralateral side (). Based on the patient's history and physical examination, we suspected that the extension deficit resulted from arthrogenic muscle inhibition. A set of exercises was performed, using the technique described by Delaloye et al. [], which usually results in full restoration of the knee extension: the patient was initially placed in prone position, with the feet off the stretcher, and asked to perform active contraction of the hamstrings. The contraction should be held for 2 to 3 seconds. Between contractions, the patient was asked to completely relax the hamstrings. This sequence of exercises was performed repeatedly until fatigue was observed, at which point, a complete hamstring relaxation had occurred. Once full passive extension was recovered, the patient was placed in dorsal decubitus, with the trunk elevated to 90 degrees and with the lower limb in extension. In this position, the patient was instructed to perform isometric contractions of the quadriceps (vastus medialis) until he succeeded in performing an adequate contraction. The patient in our report presented complete extension after approximately 7 min of the resisted exercises ().
pmc-6304829-1	A 60-year-old man was admitted to the internal department of our hospital due to thoracic discomfort, vertigo, nausea, and ataxia. After excluding acute coronary artery disease, he was referred to us because of the progression of the neurological symptoms during his one-week stationary therapy in the internal department. On clinical examination, he demonstrated a remarkable limb and truck ataxia, a rest, postural, and intention tremor, a severe dysarthria, nystagmus, and a mild cognitive impairment. The patient could not walk or eat unassisted. His current oral medication consisted of acetylsalicylic acid, pantoprazole 40 mg/d, atorvastatin, spironolactone, opipramol, Ferro Sanol, and ramipril. His medical history included hypertension, coronary artery disease, an episode of gastrointestinal bleeding by angiodysplasia in 2015, and pulmonary embolism in 2013. In addition, he had a medical history of persistent diarrhea over the last two years without any organic etiology, a vitamin D deficiency in spite of substitution, and recurrent hypokalemia. The patient was a habitual drinker consuming two glasses of wine daily. Six months ago, he was hospitalized in another neurological department because of a one-week persistent dysarthria. An obtained cranial magnetic resonance imaging (MRI) at that time revealed a symmetric hyperintensity in both cerebellar hemispheres (). To exclude a cerebellar paraneoplastic syndrome and viral or autoimmune encephalitis, a lumbar puncture was performed. The analysis result of the cerebrospinal fluid was normal. Antibodies against NMDA-receptors, AMPA1-receptors, AMPA2-receptors, and autoantibodies against Ma2 and M2, as well as herpes simplex antibodies (HSV1- and HSV2-DNA), were not detected in the cerebrospinal fluid. A computed tomographic scan of the thorax and abdomen was unremarkable. An empirical therapy with Rocephin and aciclovir was started, but after excluding herpes simplex in the cerebrospinal fluid, the antiviral therapy was discontinued. The blood pressure was slightly high during monitoring; therefore, an antihypertensive therapy was initiated. A further coloscopy and gastroscopy revealed only a Helicobacter pylori-negative gastritis. The dysarthria improved, and the patient was discharged with the diagnosis of a possible PRES according to the cranial MRI finding. The laboratory investigations disclosed a severely low magnesium level (0.4 mg/dl; range: 1.7–2.55 mg/dl), a hypocalcemic level (1.7 mmol/l; range: 2.1–2.5 mmol/l), a normal potassium level (3.6 mmol/l; range: 3.5–5.1 mmol/l), a low hemoglobin count (12.3 g/l; range: 14–17.5 g/l), a low erythrocyte count (3.69 × 106/µl; range: 4.5–5.9 × 106/µl), a low 25-OH vitamin D level (7 ng/ml; range: 31–100 ng/ml) despite the replacement therapy, and a normal parathormone (PTH) level (22.3 pg/ml; range: 14.5–87.1 pg/ml). Sodium and phosphate levels were within the normal range. The creatine kinase level was high (450 U/l; range <174 U/I). The other laboratory tests including serum electrophoresis were within the normal range. During the stationary therapy, he developed a mild hypokalemia; an oral supplementation was started. The cranial MRI displayed a weak residual hyperintensity in the right cerebellar hemisphere, probably as a residual indicator of the cerebellar bihemispheric hyperintensities described in the previous external MRI (). The electroencephalography results were normal. To exclude a paraneoplastic syndrome, we performed a lumbar puncture, which revealed an unremarkable finding. Another possible cause for PRES such as high hypertension was missing. Thus, we suspected the cerebellar syndrome due to hypomagnesemia and started an intravenous magnesium supplementation and an oral calcium intake. The patient received an intravenous supplementation of 1 g magnesiumsulfat-heptahydrat (equivalent to 4.05 mmol/mg) every two days, in addition to oral supplementation of calcium and potassium. The magnesium level returned to the normal range after two weeks of supplementation, as did the calcium level within four days. The patient exhibited a clear clinical improvement of the ataxia; he could walk and eat unassisted (). After 14 days of hospitalization, the patient was discharged. The patient received poststationary magnesium intravenous supplementation three times per week for two months. Notably, excreted magnesium in the 24-hour urine specimen was normal excluding the renal waste of magnesium. However, fluctuations in magnesium levels and the clinical symptoms were still observed under the poststationary intravenous supplementation until the proton pump inhibitor (PPI) was discontinued and a therapy with ranitidine was started. Subsequently, the replacement therapy was discontinued. The patient has remained symptom-free for over five months.
pmc-6304831-1	A 5-year-old boy was consulted at the age of 7 months for hypoplasia of his right thumb and active movement disorder. He had no particularly relevant medical history. Active movement of the right thumb was impossible, and X-ray images confirmed his hypoplastic thumb. Since his parents declined surgery, we performed only follow-up observations until he was 5 years old. At this time, his right hypoplastic thumb was more prominent (). Active flexion and extension of the interphalangeal (IP) and metacarpophalangeal (MP) joint of the right thumb were impossible, and the carpometacarpal (CMC) joint was unstable. X-ray images revealed hypoplasia of the metacarpal bone and the defective CMC joint of the right thumb (). Therefore, the boy was diagnosed as having Blauth type IIIB and performed a nonvascularized, hemilongitudinal metatarsal transfer. During surgery, the left fourth metatarsal bone was cut hemilongitudinally from the head to the shaft and the lateral part was removed (Figures and ). The cut metatarsal bone was turned over and transplanted into the metacarpal bone of the right thumb. These were sutured with 5–0 polydioxanone sutures (PDS®, Ethicon) () and fixed with a 0.8 mm Kirschner wire from the distal site (). After surgery, he wore a thumb spica brace for 2 months. Immediately after surgery, the metacarpal bone was approximately 20 mm in length, including the transplanted bone. The epiphyseal line was observed, and the metacarpal bone grew to approximately 28 mm in length within 2 years of surgery (). The growth of the right thumb was confirmed via gross observation (), and the right thumb had stabilized, thereby enabling pinch and opposition. He can hold a pen and push the buttons on a portable game machine. (). Moreover, readily notable growth disorder of the donor toe was not observed (Figures and ). Since his parents were satisfied with the thumb's functionality, opponensplasty was not performed.
pmc-6304843-1	A 93-year-old female patient with hemorrhage after tooth extraction (tooth 32) was referred to our hospital on Apr 2014. Eight days before the transfer to the hospital, her teeth were extracted by a primary dentist. Her gingival hemorrhage recession was at the same place as tooth extraction. She had no past medical history and also she took no medications. Blood clot in the socket has been increased 6 days after extraction, resulting in difficulty to have meals. On oral examination, blood clot formed a pedunculated mass on gingiva, and the size of mass was 22 mm × 15 mm × 7 mm (). As laboratory data showed that a prolonged aPTT was beyond normal range (70.7 sec), hemorrhagic diathesis was suspected. We thus consulted with a hematologist. On the 4th day after admission to hospital, aPTT cross-mixing test revealed a reduction in factor VIII (FVIII) activity levels (9%). Other hematological data including platelet count, prothrombin time (PT), and fibrinogen degradation products (FDP) were not out of the reference values. And any autoantibodies such as antinuclear antibody were not detected. Then AHA was suspected. On the same day, a nurse found that she was lying beside the bed at night. Since she complained headache, we suspected that she fell off the bed but no one knows what happened. We considered that falling form bed was one of the trigger of her subdural hemorrhage. Diffusion magnetic resonance imaging showed a high-intensity area in the frontal lobe of the cerebrum (), suggesting acute subdural hematoma. Immediately, the patient was transferred to the emergency department. On the next day, the Glasgow Coma Scale was E4V4M6. A high titer of factor VIII inhibitor (7 units/ml) confirmed the diagnosis of AHA. We discussed with a hematologist whether to use eptacog alpha (Novoseven ®), but the hematologist did not recommend to use such drug because of the patient's age and expected prognosis. The hematologist also did not recommend prednisolone therapy, and fresh frozen plasma infusion was performed. aPTT and FVIII activity levels were significantly improved 52.9 sec and 35%, respectively. Emergency physician decided not to perform surgery because of high risk due to AHA and advanced age. Hematoma was gradually increased on CT examination and decreased level of consciousness (E1V1M3). Then the patient died 13 days after admission.
pmc-6304844-1	A 35-year-old woman was referred to our hospital after having high fever and systemic joint pain for 10 days. She was admitted to our hospital for further examination and treatment. She had a past medical history of diabetes mellitus, herpes zoster, and lichen planus; her family history was unremarkable. On admission, her body temperature was 38.3°C, her blood pressure was 119/90 mmHg, her pulse rate was 110 beats/min, and the oxygen saturation in the room air was 97%. Erythematous papule appeared on the anterior chest and bilateral forearm. She had no pharyngitis, lymphadenopathy, or abdominal pain. Her total white blood cell count was 9,200/µL (neutrophils 87%, lymphocytes 7%, and atypical lymphocytes 2%), CD4+ T cell was 44.3%, CD8+ T cell was 34.5%, hemoglobin was 15.3 g/dL, and platelet count was 123,000/µL. Her laboratory test results were as follows (): C-reactive protein level, 6.83 mg/dL; aspartate transaminase, 96 U/L; alanine transaminase, 130 U/L; alkaline phosphatase, 489 U/L; γ-glutamyl transpeptidase, 349 U/L; lactate dehydrogenase, 315 U/L; total bilirubin, 1.2 mg/dL; HbA1c, 8.7%; immunoglobulin G, 1574 mg/dL; immunoglobulin A, 186 mg/dL; immunoglobulin M, 144 mg/dL. The results of the serological tests for hepatitis B and C were negative. The result of renal function test was normal. Urinalysis showed negative occult blood and urinary protein. The blood cultures showed no growth. Because the patient continued to have high fever, we performed an abdominal computed tomography (CT) scan, which revealed splenomegaly and a geographic low attenuation area in the dorsal and upper external side of the spleen (Figures and ); this finding was consistent with splenic infarction. We considered the splenic infarction to be in a hypercoagulable state. Her coagulopathy tests showed the following results: prothrombin time, 14.9 sec (normal, 10.6–14.9 sec); activated partial thromboplastin time, 33.9 sec (normal, 23.3–38.2 sec); d-dimer, 6.4 µg/mL; lupus anticoagulant, 1.05 (normal values <1.2, with dilute Russell's viper venom method); anticardiolipin antibody IgG, <8.0 U/mL; and anticardiolipin-β2-glycoprotein I complex antibody, <1.2 U/mL. There were no abnormal coagulopathy results. Because of atypical lymphocytosis and elevated transaminase, infectious mononucleosis was considered the cause of her sustained fever. The serological test for EBV antiviral capsid antigen IgM was negative at 0.1 (normal level, <0.5), antiviral capsid antigen IgG was positive at 7.5 (normal level, <0.5), and antibody to EBV nuclear antigen was positive at 4.6 (normal level, <0.5). These results suggest past infection for EBV. The serological test for CMV IgM was positive at 4.60 (normal level, <0.8), CMV IgG was slightly positive at 2.5 (normal level, <2.0), and parvovirus B19 IgM was also slightly positive at 0.99 (normal level, <0.8). The CMV antigen pp65 (antigenemia method of C10C11) was detectable at a level of 33 positive cells per 150,000 cells and 25 positive cells per 150,000 cells, which confirmed her diagnosis of acute CMV infection. The results of the human immunodeficiency virus type 1 (HIV-1) antigen/antibody and human T-cell leukemia virus type-1 (HTLV-1) antibody were negative. Although the patient was originally treated with conservative therapy, her fever persisted; therefore, she was subsequently treated with intravenous ganciclovir. The day after beginning the treatment with ganciclovir, her fever, joint pain, and erythematous papule improved (). After 13 days of ganciclovir therapy, the CMV antigen pp65 was decreased at a level of 1 positive cells per 150,000 cells and she was discharged. Two weeks after the first serological tests of the virus antibodies, a follow-up serological test was performed. CMV IgM was positive at 4.80, CMV IgG was elevated to 11.7, and parvovirus B19 IgM was elevated to 2.38. Acute parvovirus infection was confirmed by the increasing level of parvovirus B19 IgM antibody. Seven weeks after discharge, we performed an additional abdominal CT scan. The splenic infarction area was decreased without atrophy, and splenomegaly was improved (Figures and ).
pmc-6304848-1	A 13-year-old female initially presented with a history of pain and swelling along her right distal fibula. A physical exam was remarkable for point tenderness along the distal fibula with no skin changes and an otherwise normal neurovascular examination. Radiographs obtained demonstrated a lytic, expansile, geographic lesion with no cortical disruption or periosteal reaction (). MRI revealed a multiloculated, minimally enhancing, expansile lesion (Figures and ). She underwent an open biopsy which showed cyst-like spaces filled with blood surrounded by fibrous septa composed of a cellular proliferation of bland fibroblasts, scattered multinucleated giant cells, and chronic inflammation consistent with the diagnosis of an ABC (). A curettage, application of phenol, and allograft bone grafting were performed, and she was followed with serial radiographs. Six months following surgery, she presented to the clinic complaining of pain with sprinting. Radiographs obtained showed resorption of the bone graft indicating local recurrence. MRI showed a homogeneously lobulated, hyperintense lesion with multiple fluid-fluid levels confirming the recurrence (Figures and ). She underwent a repeat extended curettage with the application of phenol and bone grafting at about one year following her index procedure. Approximately eleven months following her second procedure and eighteen months following her index procedure, she again complained of pain in the right ankle with exercise. Repeat radiographs demonstrated another recurrence. Since she had failed two operative treatments, a referral to pediatric oncology was placed for the consideration of denosumab therapy for off-label use. The patient and her mother elected to proceed with the initiation of therapy after the risks including osteonecrosis of the jaw, and hypocalcemia had been discussed. The regimen used to treat giant cell tumor (GCT) was implemented which consisted of subcutaneous denosumab (120 mg) given every 4 weeks (with additional 120 mg SC doses on days 8 and 15 in cycle 1 only) for a total of 12 months []. She was administered vitamin D and calcium supplements daily and 3 months after the last denosumab dose to mitigate her risk of hypocalcemia, and labs were checked prior to each injection. Her pain improved following the initiation of treatment, and she was asymptomatic at completion of therapy. Serial radiographs were obtained throughout her treatment which showed increased mineralization and no further expansion of her lesion throughout the course of denosumab therapy (Figures and ). One year following the initiation of denosumab therapy, she underwent open biopsy, curettage with high-speed burring, and cement augmentation. The lesion was filled with thickened calcifications and septae. Her histopathology at the time of surgery showed numerous fragmented bones admixed with fragments of fibrous connective tissue with bland fibroblasts with no significant component of multinucleated giant cells present (). She has been followed for three years with clinical and radiographic examination, has resumed all normal activity without pain, and has had no recurrence of her disease (Figures and ).
pmc-6304854-1	A 22-year-old woman with a known history of giant cell tumor of the left first metatarsal was evaluated for worsening left medial midfoot pain. She had previously undergone curettage and polymethylmethacrylate (PMMA) cementation of a biopsy-proven giant cell tumor of the first metatarsal two and a half years prior at a different institution. Six months following the index surgery, she had a recurrence treated with repeat curettage, liquid nitrogen local adjuvant, and placement of bone substitute graft. After the second procedure, she was ambulatory, but occasionally used a boot for comfort and avoided high-impact activities. Physical examination demonstrated a prominent first metatarsal base and a well-healed dorsal incision. She exhibited tenderness to palpation throughout the area of the scar. Radiographs of the left foot showed an expansile, radiolucent lesion of the first metatarsal base surrounding the known cement implantation of the first metatarsal (). Magnetic resonance imaging showed a large soft-tissue mass surrounding the first metatarsal circumferentially and abutting the second metatarsal (). There was high T2 signal with no T1 signal changes at the base of the second metatarsal. Computed tomography (CT) scan demonstrated an expansile lucency at the proximal aspect of the first metatarsal base toward the dorsal lateral side (). There were some areas of cortical breach, and the bone was expanded and abutting the base of the second metatarsal. There was no evidence of direct extension into the second metatarsal or areas of osteolysis within the second metatarsal base. She was diagnosed with a second recurrence of giant cell tumor of bone of the first metatarsal base. As the tumor was recurrent, with destruction of the articular surface and little residual bone of the first metatarsal base, a wide resection of the tumor was recommended. The procedure began by harvesting iliac crest bone graft (5 cm in length, 2 cm in depth). The prior dorsal incision was extended along the entire first metatarsal and proximally across the tarsometatarsal (TMT) joint. A wide resection was performed by disarticulating the TMT joint, maintaining periosteal coverage surrounding the metatarsal, and osteotomizing the metatarsal about 4.5 cm from the TMT joint. The damaged cuneiform articular surface (from articulation with cement) was resected with a wafer osteotomy. The resection bed was treated with adjuvant thermal necrosis. Margins were extended further with 10% hydrogen peroxide. The first toe was held in appropriate length and rotation and pinned to the second metatarsal. The iliac crest graft was fashioned to fit appropriately, contouring the angles for an appropriate junction. The graft was secured with an anatomic plate and screw construct (Figures and ). Nonweight bearing was maintained until the three month postoperative visit, at which time she began weight bearing as tolerated through the heel and 50% weight bearing through the forefoot with a removable boot. Four months following her operation, she was advanced to full weight bearing as tolerated in the boot. Five months after surgery, she began weight bearing as tolerated in a regular shoe and nonimpact exercises. Nine months after surgery, plain radiographs and CT demonstrated osseous bridging at both the proximal and distal graft sites with no signs of tumor recurrence (). At one year following surgery, she denied pain in the left foot and was able to complete all activities of daily living without difficulty. Eighteen months following surgery, the patient had no left foot pain, was exercising without difficulty, and there was no radiographic evidence of recurrence. The patient was informed that data concerning the case would be submitted for publication, and she agreed.
pmc-6304856-1	A 60-year-old man with a past surgical history of C5–C7 anterior arthrodesis for cervical fracture 17 years ago was found on the floor after an unwitnessed ground-level fall, resulting in a head strike. He was taken to the local hospital in an Aspen collar with a GCS of 15 and no neurologic deficits. Routine ECG and laboratory evaluation was unremarkable except for elevated serum alcohol level. Full cervical spine computed tomography (CT) scan was performed which showed an Anderson and Montesano classification (20) type III left occipital condyle fracture (), a Levine and Edwards classification (21) type III (Jefferson) fracture with mild lateral subluxation of bilateral C1 masses (), and an asymmetric widening and slight anterior subluxation of the right AOJ (). A head CT was performed which showed no acute intracranial abnormalities. The patient was immediately transferred to a level I trauma center for further management. In the emergency department, he reported severe midline neck pain, worse with movement, and unchanged paresthesia to bilateral upper extremities which he states is his baseline. Physical exam was unremarkable except for a right forehead hematoma with overlying abrasions and tenderness to palpation over the midline posterior neck. He exhibited full strength and unchanged baseline sensation to all extremities. He denied bowel or bladder incontinence and had strong rectal tone and intact perianal sensation. Through his clinical course, he became increasingly altered and agitated, refractory to medication. He was unable to maintain spinal precautions due to his agitation, and in an attempt to protect his cervical spine, he underwent endotracheal intubation. MRI of the cervical spine was performed and showed ligamentous injury at the craniocervical junction (CCJ) (Figures and ), asymmetric left odontoid-lateral mass widening, widening and subluxation of the right AOJ (), and edema of the paravertebral soft tissues around the fracture. CT and MRI established the diagnosis of OCD in a neurologically intact patient. Due to the unstable nature of the fracture, the patient was taken to the operating room for emergent occiput-C2 posterior instrumentation and fusion (). An Aspen collar was in place at all times until surgical stabilization. Immediately, after removing the collar, Mayfield tongs were applied. Prior to patient positioning, baseline somatosensory evoked potentials (SSEPs) were obtained. Using a Jackson table turning frame, the patient was rotated into prone position. Fluoroscopic imaging was used during manual manipulation of the Mayfield apparatus to ensure no further displacement of the fracture. Occiput to C2 posterior instrumented arthrodesis was performed. Neuromonitoring remained stable during the procedure. The patient was discharged to home five days after presentation.
pmc-6304860-1	A 42-year-old man with a history of ulcerative colitis was referred to the surgical department by the gastroenterologist, after finding a lesion in the anal canal during follow-up colonoscopy (). The patient was monitored by the gastroenterology team for his ulcerative colitis and was being treated with biological factors. The patient complained of periodic anal pain, discomfort, and rectal bleeding during defecation, which started approximately 6 months earlier. On physical examination, he had an unremarkable abdominal exam. On digital and anoscopic examinations, there were third degree prolapsed hemorrhoids and an ulcerated, soft lesion on top of the 3 o'clock hemorrhoid. Colonoscopy revealed no additional findings from the rest of the rectum and colon. No biopsy was taken during colonoscopy due to the location of the lesion. Consequently, a surgical biopsy of the anal lesion was performed under local anesthesia, as a day case, without any complications. Histopathological examination showed lymphangioma of the anal canal. A wide excision of the lesion under general anesthesia followed (). The new histopathological examination revealed total excision of the lymphangioma, which was a round lesion measuring about 1.5 cm in radius and had at least 0.7 cm of distance from the closest margins of the specimen (). Immunohistochemistry was positive for CD31 and D2-40 and negative for CD34 (Figures and ). At the end of the first postoperative month, full wound healing was accomplished with no signs of recurrence.
pmc-6304863-1	A 70-year-old female complaining of persistent nasal congestion and obstruction presented to our clinic for evaluation. She denied any headache or epistaxis. Nasal endoscopy was performed which showed a posterior septal mass approaching the sphenoid sinuses bilaterally and partially obstructing the view of the nasopharynx. The overlying mucosa was intact except for a small area superiorly which showed a soft granulomatous mass protruding into the left nasal cavity. The patient was taken to the operating room for septoplasty with biopsy of the mass at an outside institution. Microscopic examination of the biopsy specimen demonstrated clusters of epithelioid-appearing cells separated by bands of fibrillary stroma. The epithelioid cells were noted to have abundant amphophilic cytoplasm, uniform, rounded nuclei with “salt and pepper” chromatin, and small nucleoli. No mitotic activity, invasion, necrosis, or calcification was seen. Immunohistochemical staining demonstrated positivity for neuron-specific enolase (NSE), chromogranin A, synaptophysin, and CD56 cell markers within the epithelioid cells. Fibrillary cells were positive for NSE, chromogranin A, S-100, glial fibrillary acid protein (GFAP), and CD56 cell markers. Based on the histological appearance and immunohistochemical staining, a diagnosis of paraganglioma was made. The patient was referred to our institution for further management. Preoperative CT imaging showed a smoothly marginated, soft tissue density mass centered at the posterior nasal septum with extension into the nasopharynx and bulging into the right sphenoid sinus (). Severe thinning and smooth remodeling of the anterior wall of the sphenoid sinus and anterior clivus were seen. MRI imaging demonstrated hyperintense signaling of the mass on T1-weighted images with a peripheral rim of hypointense signaling on T2-weighted imaging suggestive of a capsule. An endoscopic resection of the mass was performed. Intraoperatively, a large mass was seen in the posterior aspect of the septum, bulging into the bilateral nasal cavities and extending into the sphenoid sinuses (). Erosion of the bone of the rostrum and anterior face of the sphenoid were also seen. Complete resection of the mass was achieved through a posterior septectomy and bilateral sphenoidotomy with tissue removal. Postoperative histologic analysis of the specimen was consistent with a paraganglioma (). The patient has been symptom free without local recurrence 3 months following tumor resection.
pmc-6304869-1	A 74-year-old female was suffering from RA since 1993. The patient had received treatment with various DMARDs such as methotrexate (MTX), salazosulfapyridine (SASP), gold sodium thiomalate, and bucillamine (BUC). However, the administration of these agents was discontinued due to treatment-related adverse events or insufficient efficacy. In March 2009, adalimumab (ADA) (40 mg every 2 weeks) was added to low-dose prednisolone (PSL). The patient initiated prophylactic therapy with isonicotinic acid hydrazide (INH) for 6 months targeting recurrence of old pulmonary TB. A tuberculin skin test (TST) (positive) was performed prior to initiation of treatment with ADA. However, in August 2009, ADA was switched to etanercept (ETN) due to secondary failure to ADA. In October 2009, the patient was admitted to the National Sagamihara Hospital with infectious arthritis of knee or ankle caused by methicillin-resistant Staphylococcus aureus (MRSA). In April 2010, intravenous administration of vancomycin or teicoplanin (TEIC) improved the aforementioned symptoms (). RA disease activity was low with PSL 10 mg/day and SASP 1 g/day without ETN. In May 2010, the patient presented with urinary tract infection (UTI) caused by Escherichia coli with an observed increase in the levels of neutrophil CD64. Neutrophil surface CD64 expression was measured using QuantiBRITE CD64 PE/CD45 PerCP (Becton Dickinson, San Jose, CA) and a FACSCalibur flow cytometer (Becton Dickinson) as previously described []. The UTI improved following appropriate treatment for pathogenic bacteria. However, the levels of neutrophil CD64 continued to increase reaching >10,000 molecules/cell in June 2010. Subsequently, the patient had fever with bilateral infiltrative shadows appearing on a chest X-ray and positive MRSA sputum culture. TEIC was administered intravenously and the patient's temperature returned to normal, with a decrease in the levels of serum C-reactive protein (CRP). However, the levels of neutrophil CD64 increased up to 17,509 molecules/cell, and newly developed diffuse reticulonodular shadows were observed in both lung fields using a chest X-ray. Whole-body computed tomography (CT) revealed diffuse small granular shadows on both lungs and fluid accumulations (abscess) around the lumbar vertebrae Figures and . TST was negative, and the smears of sputum and gastric juice were negative for acid-fast bacilli. However, the smear of specimens obtained from the abscess by echo-guided percutaneous drainage contained acid-fast bacilli identified as Mycobacterium tuberculosis by polymerase chain reaction (PCR). The patient was diagnosed with miliary TB along with tuberculous spondylitis and transferred to a hospital which had a TB ward. In September 2010, after treatment for TB, the levels of neutrophil CD64 decreased below the cutoff value (<2000 molecules/cell) and abnormal findings on the CT scan disappeared Figures and . Sustained high levels of neutrophil CD64 were considered to be due to reactivation of LTBI.
pmc-6304869-2	A 73-year-old female was suffering from RA since 1983. In December 2008, administration of ADA 40 mg every 2 weeks was initiated due to insufficient efficacy of conventional DMARDs. Prior to initiation of ADA, a positive TST was obtained, and the patient received INH for 9 months. ADA therapy was effective against RA. However, in February 2010, she returned to the hospital with cellulitis on both legs. The cellulitis improved with administration of antibiotics (imipenem) and temporary discontinuation of ADA. In May 2011, treatment with antibiotics was associated with slight fever, elevated serum CRP, and continuous elevation of neutrophil CD64 (up to 18,831 molecules/cell) (). ADA was discontinued and further examination revealed diffuse reticulonodular shadows in the lung fields through chest X-ray and CT scan, suggesting the development of miliary TB (). Acid-fast bacilli were observed in smear preparations from sputum and gastric juice, and a sputum PCR test was positive for Mycobacterium tuberculosis. The patient was transferred to a hospital which had a TB ward. Noncaseating epithelioid granuloma was observed in bronchial and alveolar specimens obtained through bronchoscopy (). Biopsy specimens from a cellulitis-like lesion on the patient's right lower limb () also revealed erythema induratum of Bazin (). The levels of neutrophil CD64 decreased below the cutoff value after anti-TB treatment with improvement of clinical manifestations.
pmc-6304869-3	A 49-year-old female was suffering from RA since 2004. Initially, the patient received SASP and BUC. However, therapy was switched to MTX in 2007 due to insufficient efficacy. In 2009, ETN was administered without chest X-ray and TST examinations by a previous clinic doctor and was effective against RA. In October 2009, the patient visited National Sagamihara hospital and had fever (>38°C), headache, and general malaise. Although ETN was discontinued and PSL (10 mg/day) was administered, the fever persisted, the headache worsened, and vomiting was reported. The patient was admitted to the National Sagamihara Hospital in December 2009. Body temperature was approximately 40°C without manifestations on physical examinations. The levels of serum CRP were approximately 1 mg/dl, and the levels of neutrophil CD64 were highly elevated (up to 11,387 molecules/cell) (). TST was negative, and head CT scan images showed no abnormalities. A lumbar puncture revealed slightly turbid cerebrospinal fluid (CSF) with 344 white blood cells/μl (88% lymphocytes and 12% polymorphs) and low levels of glucose (29.9 mg/dl in CSF vs. 116 mg/dl) in blood. Assessment for cryptococcal antigen in the CSF was negative. Acid-fast bacteria were not detected in smear preparations from CSF and gastric juice. The following day after admission, the patient's conscious level worsened. Gd-DTPA-enhanced magnetic resonance imaging (MRI) of the brain was performed. A pia-subarachnoid enhancement was found on the fluid-attenuated inversion recovery (FLAIR) sequence, which was compatible with meningitis (). Initially, acyclovir was administered; however, the fever and level of consciousness were not improved. A lumbar puncture was performed again four days later and acid-fast bacteria were not found in the smear preparation. PCR of CSF for Mycobacterium tuberculosis was positive. The patient was diagnosed with tuberculous meningitis and transferred to a university hospital. Combination therapy of INH, rifampicin, and ethambutol resulted in gradual improvement of the level of consciousness. Six weeks later, positive results for Mycobacterium tuberculosis of cultures of gastric juice and CSF were reported. The levels of neutrophil CD64 decreased below the cutoff value after completion of anti-TB therapy.
pmc-6304870-1	A 29-year-old military male basic trainee (71 inches, 200 pounds, BMI 27.89) presented with a one-month history of atraumatic bilateral leg pain. He reported pain within the first week of initiating running at basic training. He was diagnosed with bilateral proximal tibia stress fractures at three weeks with instructions to stop impact activities. After failure of his symptoms to improve, he was referred to our facility. On presentation, he had tenderness about the medial aspect of each proximal tibia. Radiographs obtained at that time demonstrated bilateral proximal tibia stress fractures with varus alignment about each knee and articular collapse of the left tibial plateau. Metabolic labs were obtained and significant for a low vitamin D (15), but the remainders of labs including calcium, thyroid-stimulating hormone (TSH), and testosterone were unremarkable. MRI of the left knee demonstrated a medial tibial plateau fracture with two millimeters of articular depression and extension of the fracture to the tibial spine (). MRI of the right knee demonstrated a hypointense linear T2 signal surrounded by diffuse hyperintense signal suggesting a medial tibial plateau stress fracture with surrounding bone edema, without articular collapse or extension (). These fractures were at the level of the physis, and there was surrounding sclerosis on plain radiographs. Given the collapse of the articular surface in his left knee, the patient was indicated for open reduction internal fixation with allograft bone. The patient underwent the aforementioned procedure without complication, and the patient remained nonweight bearing to his bilateral lower extremities (). At the time of surgery, the bone at the fracture distal to the articular surface was softer and more friable in composition than expected for the stress fracture. It was easily debrided back to stable, healthy bone edges, and we were interested in analyzing its composition, so a biopsy was obtained and sent to the lab for analysis. Histology demonstrated nonossifying hyaline cartilage with admixed fibroconnective tissue consistent with a persistent physis (). At the six-week follow-up visit after the procedure on his left knee, the patient was still having significant pain in his right lower extremity and, after extensive counseling, elected to undergo the same procedure on the contralateral limb in an effort to return to running and continue his military career (). We suspected that a similar pathology of a persistent physis was present in the right proximal tibia and that this was contributing to his slow healing progression. Similar intraoperative pathology specimens were again obtained at the fracture site distal to the articular surface (), and these demonstrated fragments of purple to purple-gray staining matrix with chondroid metaplasia. This presence of cartilage distal to the articular surface was consistent with a persistent physis. At four-and-a-half months from the index procedure (three months from the staged procedure), the patient was ambulating without assisted devices and had painless range of motion from 0 to 120° in each knee with well-healed incisions, maintained hardware and alignment, but had not returned to impact activities. Due to his status as a basic trainee, he was released from active duty at six months' time postoperatively and was lost to follow-up.
pmc-6304886-1	A 52-year-old woman with kappa light chain multiple myeloma who was noncompliant with treatment presented one month after diagnosis with plasma cell leukemia and end-stage renal disease (ESRD) requiring hemodialysis (HD). She was treated with one cycle of bortezomib, doxorubicin, and dexamethasone and then, due to noncompliance, switched to four cycles of bortezomib, cyclophosphamide, and dexamethasone (CyBorD). She was mobilized with filgrastim followed by an autologous HSCT and melphalan (140 mg/m2) therapy. After transplantation, she developed Enterobacter and MRSA bacteremia that was treated with colistin and vancomycin for 14 days. Her total serum bilirubin level began to rise on treatment day seven and peaked at 7.8 mg/dl on treatment day 15. She also developed hepatomegaly, ascites, and had a ≥ 10% weight gain. Liver biopsy on treatment day 14 showed SOS (). She was treated with ursodiol and subsequently recovered.
pmc-6304886-2	A 53-year-old man with kappa light chain multiple myeloma and ESRD on HD was treated with five cycles of CyBorD followed by high-dose cyclophosphamide mobilization and autologous HSCT with melphalan 140 mg/m2 therapy. His subsequent course was complicated by neutropenic fever with Streptococcus sanguinis bacteremia treated with vancomycin, cefazolin, and metronidazole. He had no history of liver disease, but his total serum bilirubin level was 3.4 mg/dl at the time of transplantation and peaked on treatment day 24 at 22 mg/dl. Imaging revealed ascites. Liver biopsy on treatment day 16 was consistent with SOS (). He was treated with ursodiol and died on treatment day 25 before he could receive defibrotide under compassionate use.
pmc-6304886-3	A 57-year-old man with kappa light chain multiple myeloma was treated for approximately two years with CyBorD. The patient had ESRD and required HD. CyBorD treatment was stopped when he was diagnosed with Staphylococcus epidermidis endocarditis that was treated with vancomycin followed by ampicillin-sulbactam for one month. His myeloma subsequently relapsed and stem cells were collected with filgrastim and plerixafor mobilization. Five days after collection, he presented with jaundice and a total bilirubin level of 12 mg/dl which peaked at 15.9 mg/dl one month later. Liver histology showed SOS without myeloma (). The patient was treated with ursodiol. He was then lost to follow-up and HSCT was not performed. These three patients with multiple myeloma and ESRD were treated with alkylating agents and autologous HSCT; each had prolonged infection and developed severe SOS in case 1, very severe SOS in case 2, and moderate SOS in case 3 based on proposed grading of SOS severity by EBMT criteria [] (). Although case 3 did not have a HSCT, he was exposed to prolonged periods of alkylating agents and antibiotics such as vancomycin in the setting of a serious infection and renal dysfunction which are all underlying risk factors (). Patients with renal failure are at a greater than normal risk of developing drug-induced SOS because of altered pharmacokinetics, with marked interindividual variation [].
pmc-6304888-1	An 18-year-old previously healthy girl presented with complaint of palpitation. She has experienced palpitation 2 or 3 times a month for 3 years. She did not declare other triggering factors for palpitation with the exception of caffeine. She stated that her palpitation episode sometime lasts one hour, and it is rarely accompanied by dizziness. On physical examination, the followings were noted: normal S1 and S2 without added sounds (S3 or S4) and murmur on cardiac auscultation, blood pressure 118/76 mmHg, heart rate 78/min, and normal breathing sounds. A 12-lead electrocardiogram showed sinus rhythm with normal QRS morphology. Transthoracic echocardiography revealed a structurally normal heart with the exception of a broad false tendon within the left ventricle extending between apical lateral wall and basal septum (Figures –). Ambulatory rhythm monitoring showed no isolated premature ventricular complexes, ventricular couplets, or runs during 24 hours. She was asymptomatic during the 24 hours of ambulatory rhythm monitoring. She was advised to obtain an electrocardiogram at the time of palpitation from the nearest medical center.
pmc-6304888-2	The father of the girl in case 1, 52 years old, was admitted in our outpatient clinic due to a periodic examination of coronary artery disease. He had coronary bypass surgery history. At the time of admission, he was asymptomatic with regard to coronary artery disease. On physical examination, the followings were noted: normal S1 and S2 without added sounds (S3 or S4) and murmur on cardiac auscultation, blood pressure 132/82 mmHg, heart rate 72/min, normal breathing sounds, and no peripheral edema. A 12-lead electrocardiogram revealed nonspecific ST changes in precordial leads. Transthoracic echocardiography showed normal systolic contraction in all left ventricular wall segments. There was no evidence of left ventricular cavity enlargement or hypertrophy according to the measurements suggested by chamber quantification guideline []. During the evaluation, a left ventricular false tendon extending between apical lateral wall and basal septum was noticed (Figures –).
pmc-6304889-1	We describe the case of a 17-year-old girl with dry cough, chest pain, respiratory distress, and bronchial spasms for 4 years and presumable repeated episodes of bronchial asthma since her childhood. Computed tomography showed the intestine, mesentery, colon, and kidney inside the right hemithorax (Figures –); uniform and continuous diaphragmatic elevation throughout the hemithorax (Figures and ); discrete mediastinal displacement caused by the right kidney (); and hepatic displacement towards the left hemiabdomen causing gastric compression (). The right lung was found to be collapsed. Laparoscopy revealed visceral displacement, severe elevation of the diaphragmatic dome, and hepatic displacement; there was no diaphragmatic rupture, defined as eventration. The right colon and part of the transverse colon were adhered to the dome. The pedicle of the intrathoracic right kidney ran through the foramen of Bochdalek (). A posterolateral thoracotomy was continued at the level of the seventh intercostal space, with the hemidiaphragm being thinned, although with moderate thickness of muscle fibers (). An incision was made for hemidiaphragm plication. This was safely performed given the proximity of the peritoneal viscera (). It was sutured with prolene 0. A dual mesh of polypropylene-PTFE was placed for reinforcement and fixed at the level of diaphragmatic periphery (). There was an improvement of respiratory symptoms. The chest radiograph showed expansion of the hemidiaphragm, pulmonary field, and residual renal silhouette in the intrathoracic position (). The patient stayed in the hospital for 12 days with an adequate evolution of the respiratory symptomatology and the operative wound. The pleural effusion through the chest tube was high and remained constant in the first 4 weeks and decreased 2 weeks later, after which we had removed the thoracic tube. This drainage was probably due to the presence of foreign bodies (mesh) that led us to administer octreotide to the patient. We obtained the patient's written consent for the publication of this case.
pmc-6304895-1	A 64-year-old Moroccan female was referred to our institution for chest pain, cough, dyspnea, and a large abnormal image at the left lung field on standard radio. She had no history of smoking or exposure to any chemical substances (asbestos). Chest physical examination has noted a left pleural effusion syndrome. Thoracocentesis was immediately performed, cleaned out 1000 ml of yellow fluid which was transudative. Routine blood tests were normal. A chest CT scan revealed a large necrotic and heterogeneous mass occupying almost all the left hemithorax (). A transparietal biopsy of the mass was conducted and showed only fragmented fibrotic tissue. Therefore, a thoracoscopy exploration was performed showing a large pulmonary mass. A biopsy under thoracoscopy with histopathological study showed a proliferation of spindle cells with regions of hypercellularity admixed with hypocellular regions, accompanied by a collagenous stroma with branching hemangiopericytoma-like vessels. The neoplastic cells presented a low mitotic activity (2 mitoses per high-power field) without atypia or necrosis (). Immunohistochemical staining was positive for CD34, bcl2 (), and vimentin () but was negative for cytokeratin, SMA, desmin, and S100. The diagnosis of SFT was made. The excision of the mass was planned and a left posterolateral thoracotomy was realized. There was a hard mass invading the lower lobe of the lung with fissure encroaching and overrun of the proximal upper lobe parenchyma. Therefore, a pneumonectomy was performed (). The suture line was covered with a pedicled pleural flap in order to prevent air leakage. The patient had a total postoperative recovery and was discharged on the 10th day after surgery. At 12-month follow-up, the patient was asymptomatic and a control CT scan showed no evidence of recurrence.
pmc-6304909-1	A 24-year-old female patient in a good health condition without any chronic diseases reported to the Postgraduate Department of Prosthodontics, SGT University, Gurgaon, with a chief complaint of abnormal-looking upper front teeth since 10 years (). On examination, the retained deciduous maxillary right lateral incisor and canine and deciduous left canine were observed along with the congenitally missing permanent maxillary left lateral incisor (). Since the teeth were present in the esthetic zone, the patient demanded a fixed prosthesis that would be both functionally and esthetically acceptable. After discussing all the possible treatment options with the patient, a treatment plan was formulated which included immediate implant placement following extraction wrt the deciduous teeth (52, 53, and 63) and fixed prosthesis following intentional endodontic therapy wrt 23. Diagnostic impressions were made, and the casts were poured. Preoperative orthopantomograph () and RVGs with respect to 52, 53, and 63 were taken. After completion of phase 1 therapy, a detailed case history was recorded, the proposed treatment plan was explained, and written informed consent was taken from the patient. 1 g Augmentin™, a combination of amoxicillin and clavulanate, was given to the patient one hour prior to the surgery as a part of prophylactic antibiotic therapy. Amoxicillin fights bacteria in the body. Clavulanate potassium is a beta-lactamase inhibitor that helps prevent certain bacteria from becoming resistant to amoxicillin. The patient was draped, and an extraoral scrub procedure with povidone-iodine solution was done as an asepsis protocol. After administration of local anesthesia, the procedure was performed atraumatically with the careful use of luxators (SDI®) and periotomes (Medessa®) to avoid damage of the continuity of the alveolar ridge and with anterior forceps () with minimal tissue damage to preserve the gingiva as well as the socket. The extraction sites were examined for the presence of any bony defect, and the root measurements of the extracted teeth were taken to decide the tentative implant sizes (). Ten milliliters of venous blood was withdrawn from the antecubital vein of the patient () and immediately centrifuged (PRF Duo™) at 3000 rpm for 13 min to obtain an L-PRF clot (). The clot was condensed on a surgical plate and converted into a high-tensile-strength L-PRF membrane [] (). Leukocyte-platelet-rich fibrin (L-PRF) is a second generation of autologous platelet concentration and a fibrin mesh consisting of leukocytes, growth factors, proteins, and cytokines. L-PRF has advantages over PRP and PRGF by having a strong fibrin structure and not requiring any biochemical modification through bovine thrombin or anticoagulants. L-PRF has a very significant slow sustained release of key growth factors for at least 1 week and up to 28 days, which stimulates its environment for a significant time during early phases of wound healing. Because of its natural fibrin framework properties, growth factors can keep their activity for a relatively longer period and promote tissue regeneration faster. The preparation of osteotomy sites was carried out using the sequential order of calibrated drills recommended by the manufacturer, cooled with saline solution in external mode at a speed of 800 rpm. The osteotomy sites were prepared on the palatal and apical aspects (). The palatal orientation of the osteotomy sites was checked using paralleling pins (). The implants used were screw-type, tapered-form, two-piece, and endosseous implants belonging to the Adin Touareg™ S implant system. The implants were inserted into the bone (with an insertion torque of 35–40 Ncm) using hand tools to achieve primary stabilization. The implant surfaces were coated with PRF gel (). The implants were placed in the sockets, and cover screws were placed along with the L-PRF membrane using the poncho technique []. In this, PRF membranes were wrapped around the healing cap to favor soft tissue attachment and prevent infection and help to maintain the soft tissue profile (Figures and ). The poncho membranes can be placed around the implant collars to facilitate more rapid soft tissue healing without having to utilize a collagen barrier membrane. After ensuring the stabilization of the membrane, the final wash of the surgical site using povidone-iodine solution was done. Postoperative intraoral periapical radiograph was taken, confirming the accuracy of the placement of implants. Abutments were attached to the implant body and prepared for parallelism and adequate space. At the same day, provisional composite crowns were placed in the patient for immediate replacement of the missing front teeth due to functional and esthetic requirements. Meanwhile, intentional root canal therapy was done wrt 23. Following completion of the endodontic therapy, temporization was done wrt tooth no. 23 as well (). Postoperative care included soft diet and 0.12% chlorhexidine gluconate mouthwash twice daily starting from the next day. Systemic antibiotic and analgesic regimen including Augmentin (625 mg) TID for 5 days and the tablet Enzoflam D TID for 3 days were prescribed. A postoperative OPG was taken, and the patient was recalled after 1 week for follow-up (). After a 3-month healing period, the patient was recalled for the definitive prosthesis. Radiographic evaluation revealed good osseointegration. The single-phase impression (3M™ ESPE™ (Soft) Monophase Polyether Impression Material) of implant transfers was made with an open tray technique, and a jig trial was done prior to prosthesis fabrication (). The composite crowns were replaced with layered zirconia crowns and cemented with a resin cement (Calibra®, Dentsply Sirona) (). Follow-up was done after 3-, 6-, and 12-month intervals (). A comparison of pre- and postprocedure radiographs clearly revealed elevated peri-implant marginal bone in response to the action of loading forces. A very good esthetic result of this treatment was achieved by the preservation of gingival papillae.
pmc-6304919-1	A 33-year-old female was admitted at our institution for an episode of tonic seizure. She was diagnosed a month earlier with SLE after she presented with a photosensitive rash, arthritis, anemia, lymphocytopenia, albuminuria, hematuria, and positive antinuclear antibodies. At the outpatient clinic, she was initially started on prednisone at 1 mg/kg/day, hydroxychloroquine, and antihypertensive medications, to which she was strictly adherent. She claims to have had no previous episodes of headache, irritability, cognitive changes, or seizures, but reported poor sleep for the past week. On initial evaluation, blood pressure was elevated at 160/100 mmHg. Other vital signs were normal. Pertinent physical examination findings included facial acneiform lesions, moon facies, and supraclavicular fullness. She also had grade 1 bipedal edema and left shoulder tenderness. The initial neurologic examination was unremarkable. Initial laboratory work-up revealed microcytic, hypochromic anemia (hemoglobin of 99 g/L), and thrombocytopenia (platelet count of 100 × 109/L). Direct and indirect Coombs test was positive. Serum creatinine and electrolytes were normal. Urinalysis showed +3 proteinuria, mild pyuria, and coarse granular casts. Total 24-hour urine protein was elevated at 4.47 grams. Assessment at this time was neuropsychiatric SLE with hematologic and renal lupus activity and poorly controlled hypertension. Prednisone was shifted to hydrocortisone 100 mg IV bolus every 8 hours, and combination of antihypertensive agents was continued. Mycophenolate mofetil at 2 g/day was also started. On the second hospital day, the patient developed sudden-onset holocranial headache, confusion, and bilateral total loss of vision, which started out as blurring of peripheral visual fields a few hours prior. Blood pressure at this time was 190/110 mmHg. On examination, the patient was disoriented to time and place. Aside from bilateral total loss of vision, the rest of cranial nerve exam was normal. Muscle strength, deep tendon reflexes, and sensation were normal. Physical examination was unremarkable save for the presence of facial acneiform lesions, moon facies, and supraclavicular fullness which were already noted on admission. The patient was referred to neurology and ophthalmology for comanagement. Ophthalmology noted findings of bilateral optic atrophy and pathologic myopia. Neurology gave an initial assessment of posterior reversible encephalopathy syndrome (PRES) after noting similar neurologic findings. Contrast-enhanced cranial CT scan revealed acute parenchymal hemorrhage on the right occipital lobe amounting to 18.4 cc, with extension to the right parietal lobe, surrounding cerebral edema, subfalcine herniation, and beginning uncal herniation (). Possible acute infarcts at the bilateral occipital and parietal lobes, which were initially thought to be due to compression of posterior circulation vessels by the hemorrhagic focus, were also considered. The patient was transferred to the intensive care unit for closer monitoring. Medical intracranial pressure- (ICP-) lowering treatment and strict blood pressure control were immediately instituted. Mannitol intravenous boluses, levetiracetam, and lactulose were started. Nicardipine drip was titrated to maintain systolic BP below 140 mmHg and mean arterial pressures between 110 and 120 mmHg. Oral antihypertensives were also carefully uptitrated. Neurosurgery was also called upon for comanagement. A ruptured arteriovenous malformation was entertained, and a 4-vessel angiogram was ordered. She was also worked up for antiphospholipid antibody syndrome (APAS). However, Kaolin clotting time (KCT) and diluted Russell viper venom time (DRVVT) levels were normal. Further work-up included a 2D-echocardiogram which revealed an ejection fraction of 71%, eccentric hypertrophy with good wall motion and contractility, and a small pericardial effusion and no signs of myocarditis or rheologic stasis. In the days that followed, the patient reported gradual improvement in vision and headaches decreased in intensity and frequency. A repeat CT scan five days postictus revealed decreased cerebral edema especially on the left hemisphere and a relative decrease in midline shift (). Four-vessel angiogram showed no evidence of arteriovenous malformation and only showed poor parenchymal staining in the right parietal region due to the hematoma. Cranial MRI (done without contrast due to financial constraints) at seven days postictus revealed a 4.6 × 4.3 × 2.5 cm parenchymal hematoma in the right parietooccipital area with a volume of 26 cc, compressing the occipital horn of the right lateral ventricle (). The hematoma was peripherally hyperintense and centrally hypointense on T1-weighted images, with surrounding areas of encephalomalacia. Patchy foci of T2 FLAIR hyperintensities are seen in the cortical and subcortical regions of the occipital and posterior parietal lobes bilaterally. These findings are consistent with PRES. On follow-up six weeks postictus, the patient had gained her premorbid visual capacity and reported no recurrence of severe headache or seizures. She continues to be on prednisone, mycophenolate mofetil, hydroxychloroquine, amlodipine, losartan, carvedilol, and levetiracetam.
pmc-6304920-1	A 69-year-old man who suffered from pain and swelling in the bilateral groin and from frequent voiding visited our clinic. He had undergone bilateral transabdominal preperitoneal repair (B-TAPP) three years earlier at another hospital. During his physical examination, bilateral inguinal swelling was observed before urination, and he complained about micturition when we tried to reintroduce the hernia contents. A CT scan revealed that his urinary bladder was herniating into the bilateral inguinal hernias with a typical “Mickey Mouse” shape (Figures and ). From these findings, we diagnosed a recurrent bilateral bladder hernia after B-TAPP. Then, we preoperatively planned to employ the bladder takedown approach to pull the urinary bladder from the orifice and to perform median TAPP. With the patient in the supine position under general anesthesia, we inserted three trocars as shown in . Trocar placements were on the cranial side of the umbilicus compared to usual TAPP. At first, we confirmed that the lateral side of the mesh was appropriately covered by the prior mesh and that there were no recurrent indirect hernias. Then, we incised the peritoneum on the ventral side of the urinary bladder and took down the bladder to expose the hernia orifices (). Both hernia orifices were located inside of both medial umbilical folds; therefore, we intraoperatively diagnosed a recurrent bilateral supravesical bladder hernia with no lateral recurrences (). We introduced a laparoscopic self-fixating mesh (ProGrip™, Medtronic Inc., Minneapolis, MN, USA) into the peritoneal cavity and unrolled the mesh as both hernia orifices were covered. The mesh was fixed with Cooper's ligament and the rectus sheath by a mesh fixation device (AbsorbaTack™, Medtronic Inc., Minneapolis, MN, USA) to keep it from slipping (). Finally, we sutured the urinary bladder with the ventral peritoneum to close the preperitoneal space and to screen the mesh using a barbed suture device (V-Loc™ 180, Medtronic Inc., Minneapolis, MN, USA) (). The operative time was 132 minutes, and the total blood loss was 2 mL. We included only median mesh repair for bilateral recurrent inguinal hernias as the name of the median TAPP procedure. The patient was discharged on postoperative day 3 without any complications, and his preoperative symptoms disappeared. A postoperative CT showed no recurrence of the bilateral supravesical bladder hernias ().
pmc-6304925-1	A 28-year-old male was referred to our cardiology clinic for evaluation of a dilated IVC incidentally noted on liver ultrasound. The patient had recently been diagnosed with chronic hepatitis B on screening lab studies done at the local health department. The patient was asymptomatic and had no other chronic medical conditions. His social history was pertinent for multiple same-sex partners. A screening HIV test was negative. He had no family history of heart disease. As part of hepatitis work-up, the patient underwent liver ultrasound, which revealed dilated IVC and hepatic veins (). Liver biopsy showed evidence of chronic hepatitis but no elements of cirrhosis. He was subsequently referred to cardiology for further evaluation due to concern for elevated right-sided heart pressures. Vital signs were unremarkable with blood pressure 106/62 mmHg and a pulse of 52. He had normal body habitus (body mass index of 25.8 kg/m2). His physical exam showed no evidence of jugular venous distention, lower extremity edema, or abdominal distention, and his cardiac exam revealed regular rate and rhythm with no murmurs or gallops. Electrocardiogram showed sinus bradycardia with normal axis, no conduction delays, and no repolarization abnormalities. Labs were pertinent for AST/ALT elevations to 200 s but normal renal function and normal brain natriuretic peptide (BNP) level. The patient subsequently underwent a transthoracic echocardiogram. This showed mildly enlarged biventricular cavity (LVIDd 6.0 cm, basal RVIDd 4.50 cm) with normal systolic function (LVEF 55–60%, TAPSE 3.10 cm, TV S′ 13.0 cm/sec, and RV fractional area change of 47%) and normal diastolic function (MV E velocity 82.56 cm/s, MV A velocity 39.53 cm/s, MV E/A 2.09, MV e′ septal 15.00 cm/s, MV e′ lateral 16.00 cm/s, E/E′ ratio 5.42, estimated PASP 34, and LA volume index 41.31 mL/m2). There were no significant valvular abnormalities except mild mitral and tricuspid regurgitation. RA was normal in size. The IVC diameter was increased at 2.7–3.0 cm and demonstrated <50% collapse with inspiration (Figures and : 2D and M-mode images with markings). Dilated hepatic vein was again demonstrated, and the Doppler-based hepatic vein flow pattern showed slightly greater diastolic velocity (Vd) than systolic velocity (Vs) (). There was no narrowing of the IVC suggestive of external compression. Given these abnormal findings suggestive of increased RAP despite an otherwise healthy young male without signs of heart failure, a RHC was performed. Hemodynamics were found to be within normal limits: mean RAP of 8 mmHg, mean pulmonary artery pressure of 19 mmHg, pulmonary capillary wedge pressure (PCWP) of 12 mmHg, and thermodilutional/Fick CI of 3.31/2.82 L/min/m2, respectively.
pmc-6305014-1	An 8-year-old boy with Noonan syndrome, genetically confirmed by a de novo germline heterozygous mutation of PTPN11 (c.854 T>C), was referred for a swelling of the left knee. His medical history was marked by a neonatal hypertrophic cardiomyopathy and pulmonary valve stenosis (which needed balloon dilatation procedures and surgery), a transcatheter closure of an atrial septal defect, an orchidopexy for right cryptorchidism, a right renal malrotation, a percutaneous endoscopic gastrostomy for eating disorders during 4 years, a slight delay of language, a cystic lymphatic malformation of the right chest wall, and finally, a short stature which required a growth hormone treatment for a sustainable growth. The clinical examination revealed classical features of this syndrome including small hypertelorism, mild ptosis, downslanting palpebral fissures, low-set and posteriorly angulated ears, high arched palate, short neck, and pectus excavatum (). We also noticed an extensive swelling on the lateral side of his left knee without any functional disability or pain. An ultrasound imaging showed a joint effusion with villous hyperplasia of the synovial lining in his posterior part (). The patient underwent a joint puncture, which revealed hemarthrosis. Diagnosis of PVS was then suspected by magnetic resonance imaging based on an important joint effusion () and villonodular thickening of the synovial membrane with hemosiderin deposition (). Arthroscopic total synovectomy was successfully performed. Histopathology of the synovial tissue showed villous hyperplasia on macroscopic examination and multinucleated giant cells in a background of fibrous connective tissue with numerous blood vessels and inflammatory infiltrates with hemosiderin-laden macrophages on microscopic examination. The patient recovered a complete mobility of his knee with intensive physiotherapy. Almost one year later, he developed a painless tumefaction of the anterior surface of both elbows (). Considering his medical history, the diagnosis of PVS was mentioned again and was suspected by the MRI. A bilateral total surgical synovectomy was performed in a single-stage procedure, as the main part of the PVS was extra-articular, thereby limiting the use of arthroscopy. The patient had a complete recovery of his elbows' functional abilities. At this time, no relapses have occurred on his left knee or both elbows and we did not notice any new lesion.
pmc-6305016-1	A 55-year-old female patient with past medical history of osteoporosis and hyperlipidemia was admitted to our department for a 2-month history of high-grade fever, up to 39°C, mainly occurring in the evening, which was responding to acetaminophen. She denied night sweats, anorexia, fatigue, weight loss, chest pain, shortness of breath, other joint pain, abdominal pain, recent travel, or a family history of autoimmune disease, although she reported traumatic dental procedure 6 months prior to admission. On presentation, her vital signs revealed a temperature of 36.7°C, heart rate of 74 bpm, and blood pressure of 100/70 mmHg. Her physical examination was unremarkable, except for a systolic heart murmur, heard best over the aortic, pulmonic, and mitral area with radiation into the neck. Laboratory studies revealed thrombocytopenia with 123.000 μL platelets, white blood cell count of 4.3 × 109 L with neutrophils as the predominant type, and mild normocytic anemia (Hct: 34.7%; Hb: 11.7 g/d). The C-reactive protein (CRP) was 1.43 mg/dL (nl: <0.5), the erythrocyte sedimentation rate (ESR) was 32 mm/h, and creatine phosphokinase (CPK) was also elevated as 335 U/L (reference range: <180 U/L). From three blood cultures obtained on the 1st, 2nd, and 3rd day of her hospitalization, when she was febrile, Streptococcus thoraltensis was identified, while infection caused by Brucella, Mycobacterium tuberculosis, Coxiella, and Leishmania was excluded. The suspicion of an infective endocarditis (IE) was raised, and a transthoracic and transesophageal echo was performed. However, there was no evidence of IE, and only mild aortic stenosis was revealed. A panoramic X-ray showed no lesions. Additionally, as part of the diagnostic procedure, a chest, abdomen, and pelvis computed tomography (CT) scan was performed and revealed no abscesses and masses. Due to the fact that the patient continued to have high-grade fevers and the systolic heart murmur, empirical antibiotic treatment with ampicillin/sulbactam and gentamicin was initiated on day 4. Susceptibility testing was performed on the initial isolate and revealed intermediate sensitivity to these agents, as determined by the E-test method (). The patient responded 48 hours after the initiation of the treatment. The duration of the antibiotic therapy was fourteen days. The patient had experienced no recurrence of fever, the subsequent blood cultures were negative, and the inflammation markers decreased (CRP: 0.3 mg/dl; ESR: 10 mm/h).
pmc-6305018-1	A 43-year-old female with a past medical history of severe allergy-induced asthma and chronic nasal drip presented to the clinic with worsening cough and chest tightness for 10 days and was treated for bronchitis with steroids and antibiotics. She then presented to the emergency department with severe and acutely worsening shortness of breath, sudden onset pleuritic chest pain, and sharp radiating pain between both shoulder blades with deep inspiration. At time of presentation, the patient was afebrile with vital signs within the normal limits. Lab work was insignificant with negative leukocyte count and negative cardiac enzymes. A chest X-ray demonstrated an abnormal right cardiomediastinal silhouette with large opacity over the right mediastinum adjacent to the right atrial border. A follow-up CT scan revealed a large right-sided mass adjacent to the right atrium and extending into the right chest measuring 5.1 cm × 9 cm × 4.3 cm (). Her last imaging study was a fluoroscopy study 10 years ago that showed no indications for a mediastinal mass. An echocardiogram revealed a normal ejection fraction (55–59%), no wall motion abnormalities, and a cyst near the right atrium. The patient had continued pleuritic chest pain and difficulty breathing and the decision was made to perform video-assisted thoracoscopic surgery (VATS) for pericardial cyst removal. The patient underwent general anesthesia with a 37 French left-sided double-lumen tube. Standard ASA monitors were applied. Two large-bore peripheral IVs and an arterial line were placed for continuous blood pressure monitoring. Intraoperatively, a large cystic lesion was adherent to the pericardium (). There was no solid component and no obvious communication with the pericardium. Part of the cyst wall was left on the phrenic nerve to preserve it. The patient tolerated the procedure well, had no postoperative complications, and was discharged home on postoperative day number two. The final pathology report revealed benign, acute inflammatory pericardial cyst.
pmc-6305023-1	A frail 86-year-old female, presenting with dyspnea on exertion with elevated brain-type natriuretic peptide (BNP) level of >900, at high surgical risk (the Society of Thoracic Surgeons risk score 9.8%), was referred to our institution to consider treatment for severe AS. Transthoracic echocardiography (TTE) revealed not only severe AS (aortic valve area was 0.58 cm2, and peak velocity was 4.0 m/s) but also diffuse left ventricular hypertrophy except posterior wall (Maron type III hypertrophic cardiomyopathy) and LVOT obstruction with systolic anterior motion (SAM) of the mitral valve, leading to moderate mitral regurgitation (MR). Peak velocity was 2.9 m/s, and mean pressure gradient was 32 mmHg at the LVOT during the Valsalva maneuver. After administration of a beta-blocker (bisoprolol 1.25 mg/day), LVOT obstruction and SAM disappeared, and MR was reduced to mild degree. Since peak velocity across the aortic valve and BNP level were still high, TAVI was planned to treat AS. Coronary angiography confirmed the first major septal branch perfusing the basal septum (). Thus, ASA was considered as a rescue option for recurrence of LVOT obstruction. The 23 mm SAPIEN 3 valve (Edwards Lifesciences, Irvine, CA, USA) was successfully implanted via transfemoral approach with general anesthesia and transesophageal echocardiography (TEE) guidance, under continuous infusion of beta-blocker (landiolol) and volume load. Five minutes after implantation, there was no obvious LVOT obstruction and SAM (Figures –). However, 15 minutes later, TEE clearly showed SAM and severe MR, and pressure gradient was >50 mmHg at the LVOT, even under increased dose of beta-blockers (Figures –). Because the patient's hemodynamic status became rapidly unstable, we decided to perform emergent ASA. Through a 2 mm over-the-wire balloon, microbubble contrast was injected into the first septal branch to confirm its perfusion area in the septum, which was located on the opposite side of SAM, using TEE (). After injecting a total of 3.5 ml absolute alcohol into the septal branch (), total occlusion was confirmed by coronary angiography (), and the pressure gradient at the LVOT was decreased below 10 mmHg (). Final TEE and TTE showed no LVOT obstruction or SAM and reduced MR. After ASA, complete atrioventricular block occurred, and a permanent pacemaker was implanted 3 days later. At 6-month follow-up, TTE showed good bioprosthetic valve function, regional hypokinesis of the basal-mid septum, and no evidence of LVOT obstruction.
pmc-6305029-1	Patient R.C., 52-year-old male subject, sought for dental treatment demonstrating dissatisfaction with the upper anterior teeth aesthetics, which had extensive composite resin restorations, pigmentation, spots, and infiltration (). After the anamnesis, as well as the X-rays, photographs and upper and lower arches' evaluation (), the case was prepared and an aesthetic rehabilitation treatment was proposed, consisting of a ceramic crown, with zirconia infrastructure in element 15 and laminated veneers, with feldspathic ceramics in elements 11, 12, 13, 14, 21, 22, 23, 24, and 25. Following the references from the digital smile design, which is performed using pictures of the face and smile of the patient and a computer program, PowerPoint (Microsoft) or Keynote (Mac), it is possible to correct positioning and minor glitches using smile lines and median with teeth proportionality; a diagnostic wax-up of the upper model was produced (), and based on it, silicon guides were made to create the mock-up, guide the enamel/dentin preparation, and subsequently assist in the preparation of a temporary crown with bis-acryl resin. Considering tooth 15, a metal-free preparation was made to cover the full crown with zirconia infrastructure; elements 14, 24, and 25 were chosen for inverted-type 4/5 preparations, and for the anterior teeth, tooth preparation for laminated veneers with incisal wear and no overlap was considered for the treatment (). When the tooth preparation was finalized, gingival separation was done by applying the double-wire technique. For this, wires no. 000 and no. 00 (Ultrapak, Ultradent), embedded in hemostatic solution (Hemostop, Dentsply), were used. Considering the molding process, at the time of the light A-silicone insertion, the second wire (no. 00) was removed and the material flowed into the gingival sulcus, copying the terminus region. Soon after, the tray with the putty A-silicone was positioned (Flexitime, Heareus Kulzer) (). After analyzing the mold quality, the temporary crowns were prepared with A3-colored bis-acryl resin (Structur, Voco), using the silicone guide built on the model with diagnostic wax-up (). The working model was obtained using stone rock type IV (Elite Rock, Zhermack) and then punched () through the Accutrac system (Coltene/Whaledent), in laboratory, for later duplication and confection of the veneers in feldspathic ceramics (IPS Empress II, Ivoclar Vivadent) (). Once tested, adjusted, and approved, the cement agent color was chosen. In order to do so, temporaries were removed and the cement was tested using the try-in system (Variolink II, Ivoclar Vivadent), which are glycerin-based compounds that simulate the cement final color. Thus, based on this choice, the cement was finally selected. Once the cement color (color A3) was chosen, pieces were taken for cementation. Firstly, the try-in was removed, washing it under running water, and, subsequently, 10% hydrofluoric acid was applied (Ceramic Etching Gel, Ivoclar) for 60 seconds. The samples were then washed thoroughly in running water, and after a two-hour drying process, two different layers of silane (Monobond-Ivoclar) were applied for 60 seconds. After the piece preparation, isolation and gingival separation were done, using retractor wire # 000 (Ultrapak, Ultradent), embedded in hemostatic solution (aluminum chloride, Dentsply). The process was then accomplished on the buccal face of the teeth that would receive the veneer. The dental substrate was degreased, with detergent solution (Tergensol, Inodon), conditioned with 37% phosphoric acid (Condac, FGM) for 15 seconds, and then washed for 45 seconds for subsequent drying, leaving the substrate slightly moist. The adhesive system (Gluma, Heraeus Kulzer) was applied for 30 seconds, waiting for the adhesive to penetrate in the conditioned dentin tubules. A light air jet was applied, and then, each tooth was light cured for 30 seconds. The light-cured resin cement (Variolink II, Ivoclar Vivadent) was activated and placed inside the pieces that were placed into position and light cured again for additional two seconds. The excess cement was removed, using a scalpel blade, and the curing cycle was terminated (40 seconds on each side). Finally, a glycerin layer (Liquid Strip, Ivoclair Vivadent) was applied, on the cervical region, between the union piece and tooth, and resin cement was light cured for another 20 seconds, aiming at blocking the oxygen entrance. The excess cement was removed with the aid of scalpel blade number 15c (Solidor) and polished with silicone cups and felt disks (). After completing the case, the patient evaluated the final result of the installed work, comparing the before and after the installation of the ceramic veneers, and he was very satisfied with the result.
pmc-6305034-1	A 31-year-old female presented with abdominal distention, leg swelling, and dyspnea on exertion. She denied past medical history except for a thyroid condition for which she was on and off of medications. Examination revealed conjunctival pallor and scleral icterus. She was afebrile and normotensive but tachycardic with heart rate 160-190/minute. Cardiovascular exam revealed an irregular rhythm, systolic murmur at the lower left sternal border and cardiac apex, and an elevated JVP. Chest radiograph displayed cardiomegaly. EKG showed atrial fibrillation with rapid ventricular response (). She received metoprolol with adequate rate control. Brain natriuretic peptide was over 4000. Urine drug screen was negative. Transthoracic echocardiogram (TTE) reported an ejection fraction (EF) of 43%, global hypokinesia, grade 2 diastolic dysfunction, anterior mitral valve prolapse (MVP), very severe mitral regurgitation (MR), severe tricuspid regurgitation (TR), severely dilated atria, and right ventricular enlargement with moderate PH. Thyroid work-up revealed suppressed TSH at <0.005 (ref: 0.45 – 5.33) uIU/ml, elevated free T4 at 5.36 (ref: 0.58 – 1.64) ng/dl, free T3 of 28.31 (ref: 2.2-4.10) pg/ml along with elevated anti-thyroglobulin antibodies at 12 (ref: ≤4) IU/ml, thyroid peroxidase antibodies at 3841 (ref: ≤8) IU/ml, and thyroid-stimulating immunoglobulin >500% (≤122%), suggesting Graves' thyrotoxicosis. Thyroid ultrasound showed significantly enlarged, mildly heterogeneous lobes without discrete nodules. Methimazole was started with plan for subsequent radioactive iodine ablation. Other notable labs included elevated alkaline phosphatase, bilirubin, and international normalized ratio with normal transaminases. Subsequent ultrasound of the abdomen showed moderate ascites with liver architecture suggestive of cirrhosis. Paracentesis removed 4.4 l of ascitic fluid with serum ascitic albumin gradient (SAAG) over 1.1, suggesting portal hypertension. She denied alcohol use and had no other risk factors for nonalcoholic liver disease including obesity (low normal body mass index of 18.4 kg/m2), systemic hypertension, dyslipidemia, or diabetes. Work-up was negative for immune causes of cirrhosis, including antinuclear antibody (ANA), ceruloplasmin, alpha-1-antitrypsin (AAT), anti-mitochondrial antibody (AMA), and anti-smooth muscle antibody (ASMA). Ferritin level was within range, and the hepatitis panel was negative. The patient was discharged home on a beta-blocker and diuretics. Follow-up office visit showed improving thyroid functions TSH at <0.005 (ref: 0.45 – 5.33) uIU/ml but normal free T4 at 0.60 (ref: 0.58 – 1.64) ng/dl, and slightly elevated free T3 at 4.28 (ref: 2.20 – 4.10) pg/ml. EKG showed normal sinus rhythm and normal rate. Subsequent echocardiogram at 2 months showed normal left ventricular systolic function with EF of 61%, no regional wall motion abnormalities, normal diastolic function, moderate MR and TR, and top-normal right-sided pressures. Ultrasound of the abdomen at that time showed persistent appearance of cirrhosis with improved ascites.
pmc-6305046-1	A 72-year-old male presented with a left groin lump which grew steadily over the course of several months. He denied any fever, chills, night sweats, or weight loss. CT scan revealed a 5.3 cm left inguinal mass, highly suspicious for lymphoma. No other lymphadenopathy was identified in the abdomen or pelvis. His white blood cell count was 8.2 × 103/μL, hemoglobin 14.8 g/dL, hematocrit 45%, and platelet count 219 × 103/μL. The differential count in the peripheral blood was 34% neutrophils, 2% bands, 57% lymphocytes, 5% monocytes, and 2% eosinophils. An excisional biopsy of the left inguinal mass was performed. Flow cytometric phenotyping identified the presence of two distinct, phenotypically abnormal B-cell populations (). The minority population was composed of small cells expressing moderate CD19, dim CD20, moderate CD5, dim CD11c, and dim CD23 with no definitive surface light chain expression. The majority population was composed of medium- to large-sized cells expressing moderate CD19, moderate CD20, dim to moderate CD5, and moderate CD10 along with a bright surface kappa light chain restriction. This majority population did not express CD11c or CD23. Morphologic review of hematoxylin and eosin (H&E) stained fixed tissue sections and immunohistochemistry (IHC) confirmed the presence of two B-cell populations (). Expanses of large lymphoid cells with vesicular chromatin and nucleoli stained positive for CD20, CD3, CD5, CD10, CyclinD1 (BCL-1), and SOX-11 with a high estimated proliferation rate (Ki-67) of 70%. A second population of small B-cells between the larger cells stained less intense for CD20, coexpressing CD5 and CD23. These smaller cells were negative for CD3, CD10, CyclinD1 (BCL-1), and SOX-11 with a low estimated proliferation rate (Ki-67) of <10%. Flow cytometric phenotyping of the staging bone marrow aspirate detected small B-cells with features most often associated with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (). These features included small B-cells coexpressing moderate intensity CD19, dim CD20, dim CD5, dim CD11c, dim CD23, and no definitive surface light chain expression. These B-cells did not express CD3, CD10, or FMC-7. Morphologically, there were multiple small aggregates in the core and clot sections composed of B-cells staining for CD5 without CD3, CD10, or CyclinD1 (BCL-1). Microdissection of the lymph node into MCL and SLL components based on an H&E stain was performed in order to perform additional FISH testing for IgH/CCND1 and B- and T-cell gene rearrangement studies. B-cell gene rearrangements for 3 framework regions of the heavy chain (FR-JH), VK-JK, and VK-KDE light chain and T-cell rearrangements for VB-JB1-DB1, VB-JB2, V1-8-J1.3–2.3, V9-J1.3–2.3, and V10-J1.3–2.3 were performed using polymerase chain reaction (PCR). The same molecular studies were performed on the aspirate clot section of the bone marrow (Tables and ). B-cell gene rearrangement studies on the bone marrow aspirate clot (SLL only) revealed the following prominent peaks: 2 peaks for FR2-JH, 2 peaks for FR3-JH, 2 peaks for DH-JH, 1 peak for DH7-JH, 2 peaks for VK-JK, and 1 peak for VK-KDE. All of these clonal peaks were also seen in the MCL component of the lymph node. There was an additional prominent peak for FR1-JH, 2 additional peaks for DH-JH, and 2 for VK-JK in the MCL component of the lymph node. T-cell gene rearrangements were detected in both the bone marrow aspirate clot and the MCL component of the lymph node. Two identical clonal peaks for VB-JB2-Db2 and one identical peak for VB-JB1-Db1 were detected in the bone marrow aspirate and MCL component of the lymph node. Both the bone marrow aspirate clot and the MCL component of the lymph node showed additional, separate prominent peaks for other T-cell primer sets. Fluorescence in situ hybridization (FISH) using dual-fusion probes confirmed the presence of the t(11;14)(q13;q32)–IgH/CCND1 translocation consistent with MCL in the lymph node. The bone marrow aspirate clot was negative. Based on all of the results, the diagnosis of lymph node involvement by clonally related blastoid variant mantle cell lymphoma with aberrant CD10 and CD3 and small lymphocytic lymphoma was made. The staging marrow was involved by SLL, but not by MCL.
pmc-6305058-1	A 35-year-old female patient presenting a unilateral skeletal crossbite in maximum intercuspation attended the postgraduation orthodontic clinics with the main concern of “crooked smile” and had never undergone orthodontic treatment. The patient was diagnosed with mesofacial facial type, presenting facial asymmetry in the lower facial third, with mandibular deviation to the right side in relation to the facial midline. During smile, an increased buccal corridor was observed, confirming maxillary constriction and crossbite on the right side. Profile analysis showed a straight orthognathic profile. Intraoral photos showed canines in Class I relationship with unilateral crossbite on the right side, 1 mm overjet, 2 mm overbite, triangular shape of the upper arch, and oval shape in the lower arch (). Upper right second premolar showed a shape anomaly, and teeth 25 and 46 were absent. In clinical examination, a functional shift was observed when evaluating mandibular movement patterns so that centric relation and centric occlusion were not coincident. Lateral and panoramic x-rays show good inclination of upper incisors, lower incisors slightly proclined, and absence of all third molars (). Ricketts cephalometric analysis indicated a mesofacial, skeletal class I patient with protruded and slightly extruded lower incisors, slightly protruded upper incisors, and mesialized mandibular first molars. In the soft and hard tissue integration analysis, centroid-based wits showed skeletal Class I and all angles within the normal limits, determining a neutral growth. The middle and lower facial thirds were balanced, and the nose, lower lip, upper lip, and soft chin are well positioned. Lip sealing was presented (). Initial orthodontic planning was to perform rapid palatal expansion with bone anchorage (). A MARPE device consisted in an expander screw (9 mm) and 4 self-drilling and self-threading miniscrews. Microimplants were 1.8 mm in diameter, and their length were 11 mm for the anterior ones (7 mm thread and 4 mm neck) and 9 mm in length for the posterior (5 mm thread and 4 mm neck) (Peclab, Belo Horizonte, Brazil). Teeth 16 and 26 were banded and transferred to the impression for laboratory procedures, according to Brunetto et al. []. The device was installed using local infiltrative anesthesia and following the procedure, a prescription of antibiotics and analgesic medication; in addition, the use of a chlorhexidine 0.12%-based mouthrinse on for a period of 7 days was recommended. Activation protocol was 1/4 of activation twice a day for 10 days []. However, immediately after the orientation of the activations, the patient reported being unable to perform turn the jackscrew expander due to great resistance to move the key in backward direction. The difficulty was related to the strong resistance of the midpalatal suture, requiring high force to manipulate the expander key from front to back. For this reason, activation attempts were then performed every other day as patient visited the clinic with no success in opening the suture. After failing to activate the MARPE device, a minimally invasive surgical method was suggested to the patient in order to reduce suture resistance and accelerate bone remodeling (Figures –). Eight bone perforations, called corticopunctures, were performed along the midpalatal suture. Prior insertion of the miniscrews, cortical bone was shallow manually pre-drilled using a 1.1 mm diameter and 4 mm bur and a contra-angle screwdriver (Peclab, Belo Horizonte, Brazil). Corticopuncture was then performed manually by inserting and removing a 9 mm titanium alloy miniscrew (5 mm double thread, 4 mm neck of length and 1.8 mm diameter). The distance between perforations was 2 mm. It is important to note that corticopunctures were only 5 mm depth in the midpalatal suture. In the anterior part of the palate perforations were done carefully in order to avoid the nasopalatine canal (). Corticopuncture procedure was done using greater palatine nerve block anesthesia. After procedure only prescription of analgesic medication for pain relief, in addition to the use of a mouthrinse based on chlorhexidine 0.12% for a period of 7 days. In this patient, corticopunctures could not be performed beneath the jackscrew of the expander since the MARPE appliance was in place, thus limiting the number of perforations. An alternative would be perforating midpalatal suture prior to MARPE and miniscrew insertion. shows a step-by-step corticopuncture method in a second patient who was treated using 11 mm Maxillary Skeletal Expander I (MSE) (Biomaterials Korea, Seoul, South Korea) and 4 miniscrews (11 mm in length and 1.5 in diameter) [, ]. For this patient, a contra-angle electric screwdriver (Model ISD900, NSK, Japan) set in 25 min−1 speed and 40 Ncm torque was used to perform the corticopunctures. After the surgical procedure, the patient was instructed to perform second activation protocol, similar to the one done previously, and better results were obtained, indicating success in splitting midpalatal suture. Images were recorded in the centric relation position, and an occlusal X-ray from the maxilla was taken. A diastema between incisors was then observed (). Cone-beam computed tomography (CBCT) scan using an extended protocol (13 cm FOV and 0.3 mm voxel) was used as the maxilla being the region of interest. Images were generated using OnDemand3D software (Cybermed Inc., Seoul, South Korea) to confirm midpalatal suture split and to evaluate whether the suture opened in a “V” shape or parallel. Later, CT exam will be used to reevaluate and plan the orthodontic phase of the treatment and future evaluation and interdisciplinary planning for implants in the region of teeth 25 and 46. CBCT evaluation showed parallel split of the midpalatal suture in a coronal view, which means that the amount of opening in the lower portion, near the cervical of the incisors, and in the upper portion of the maxilla, near the nasal cavity, was similar, measuring 2.06 mm of suture separation. In axial view, suture opening occurred more in the anterior region than in the posterior region, connoting a “V” shape. Although molars served as a support for MARPE installation, they did not show evident buccal inclination after expansion, indicating a more skeletal than dental effect (). An image in a sagittal view close to the microimplants showed that both were anchored in a bicortical engagement of the palate and the nasal cavity floor as recommended by Lee et al. [] (). The orthodontic phase of treatment included the correction of the lower midline deviation, lower right second molar uprighting, intrusion of the upper right first molar, space management for future prosthetic rehabilitation in the missing area of teeth 25 and 46, shape restoration on tooth 15, and torque control (). Final pictures showed a Class I relationship, good overjet and overbite, and no CR-CO discrepancy. Since spaces were prepared for rehabilitation, the patient was referred to implantology and prosthodontics (). Facial pictures show the maintenance of the good profile and improvement of the mandibular deviation in the frontal view. shows broader smile compared to the initial. Facial photographs during smiling showed before and after suture split, the presence of a diastema between the central incisors immediately after corticopuncture procedure and MARPE reactivations. Final pictures shows an improvement in buccal corridor during smile and also mandibular deviation ().
pmc-6305262-1	A-43-year old female with severe anemia following splenectomy previously typed as blood group A, Rh (D) negative, was referred to Immunohematology Reference Laboratory (IRL) of the Iranian Blood Transfusion Organization (IBTO), Tehran, Iran for ABO / Rh(D) typing and antibody screening test with a request for two units of RBC for transfusion in December 2013. Patient’s medical history revealed recurrent abortion and miscarriage with no history of blood transfusion. Her family history revealed that her parents had a consanguineous marriage and she had four siblings, all were alive without any suspected blood disorder, except one of the brothers that underwent splenectomy because of hereditary spherocytosis anemia. Her only previous child was a healthy fifteen-year-old boy, who was typed and was not confirmed as Rhnull phenotype. Coagulation and hematology parameters were in the normal range, except for very low hemoglobin of 3.2 g/dL. It was observed that the patient’s serum plasma reacted strongly in antibody panel cells, giving 4 + macroscopic in 37℃ phase and in the anti-human globulin phase. Auto control test result was negative. Direct Anti-globulin Test (DAT) was positive (1+) with differential anti- IgG negative and anti-C3d positive (1+). These results suggested the presence of clinically significant alloantibodies against multiple negative antigens or a high-prevalence antigen. An antibody screening test result was negative for the patient’s brother. A home-made available three-cell antigen panel (IBTO mini-panel) was used for the antibody screening procedure in which the patient's plasma was added to RBCs without papain enzyme using the Low Ionic Strength Saline (LISS). IBTO mini-3cell panel and antibody identification 11cell kit and also selected cells were validated within the two-year period using commercial CE marked Diamed kits. The antibody screening test was performed twice in parallel using IBTO produced kits and Diamed kits. The results were compared and in case of positive results, the 11cells antibody ID panel from Diamed Company was used simultaneously with IBTO 11cells antibody ID panel. IBTO homemade antibody ID panel and selected cells were used to exclude and include alloantibodies. Column agglutination method with antiglobulin gel card (INVITROGEL AHG coombs-Germany) was used for the antibody screening test. The gel cards were incubated at 37 °C for 15 minutes, and then centrifuged for 10 minutes. Standard tube methods (Bio-Rad AHG- Germany) were used for antibody identification and selected cell tests. Clinically significant alloantibodies were defined as those antibodies that potentially could cause RBC destruction based on the reactivity at 37 °C and/or anti-human globulin (AHG) phase. The patient and her brother extended phenotyping showed that they were negative for D, C, E, c, e RBC antigens, indicating they were strongly suspicious of being the rare Rhnull phenotype. Adsorption and elution studies in Anti-human globulin (AHG, CE- Immunodiagnostika, Am Seerain 13 Germany, Eschelbronn) did not reveal the presence of D, C, E, c, e, RBC antigens in the blood obtained from both patients. We performed Rh phenotyping with two sources of antisera (Diagast 251/AV.AVINEE- 59120 Loos, France and CE- Immunodiagnostika, Am Seerain 13 Germany, Eschelbronn). Positive and negative control tests were performed for each antigen according to the manufacturer’s recommendations. Based on these collective findings, we interpreted these results as being strongly suggestive of the Rhnull phenotype with a clinically significant anti-Rh29 identified in serum of the female patient whose data are shown in . Compatibility testing showed that serum from the female patient was non-reactive with her brother. Two units of RBC were collected from the brother within a 10-day period. She was transfused with the RBC units and never needed any transfusion since that date. Her brother donated two more units of RBC in 2014 and 2015. Cryopreservation was also utilized for future use.
pmc-6305263-1	A 63-year-old, female, left-handed patient presented to the Emergency Room with expressive aphasia for the last 5 hours. Her past medical history was unremarkable and she was not receiving any medications on a regular basis. Apart from aphasia, physical examination on presentation was normal. Blood samples were taken for initial laboratory evaluation and an urgent brain Computed Tomography (CT) scan was also performed. Her CT scan demonstrated an acute ischemic infarct at the left parietal lobe. At the same time, blood tests revealed severe hypercalcemia (14.1 mg/dl, reference range 8.8-10.5). According to our hospital stroke protocol, patients are considered ineligible for thrombolysis, given that more than 4 hours have passed since the onset of symptoms. Her initial therapy included intravenous administration of saline, calcitonin and zolendronic acid. During the very first hours of her hospitalization, her neurological condition worsened, developing left hemiparesis and right- sided horizontal gaze paralysis (Foville’s syndrome). A second CT scan excluded intracranial hemorrhage and a Magnetic Resonance Imaging (MRI) brain scan after 48 hours showed another acute infarct at the anatomical area of the right pons. Unfortunately, due to technical reasons, we were not able to perform a CT angiography of the intracranial vessels. Further investigation revealed high serum PTH levels (11.1 pmol/l, 1.58-6.03), marginally low serum phosphorus levels (2.7 mg/dl, 2.7-4.5), vitamin D insufficiency [25(ΟΗ)D3 22 ng/ml, 30-100] and elevated urinary calcium excretion (325 mg/24h, 100-250) (). Imaging of the neck with CT, ultrasonography and scintigraphy of the parathyroid glands were suggestive for an adenoma of the right superior parathyroid gland. Renal ultrasound revealed bilateral nephrolithiasis. Potential causes of embolic stroke were excluded, given that electrocardiography (ECG), cardiac ultrasound, carotid artery triplex ultrasound and 24-hour holter monitoring demonstrated normal findings. Common risk factors for atherosclerosis, such as hypertension, smoking, dyslipidemia and diabetes were absent. Thrombophilia screening was negative. An electroencephalography (EEG) showed normal findings. Remarkably, her MRI did not bring to light any major atherosclerotic lesions of intracranial vessels. Following the initial treatment, serum calcium levels returned to the normal range within 3 days accompanied by gradual improvement in symptoms. Ten days after admission, she was discharged with nifedipine, aspirin, normal serum calcium levels and only a mild paresis on her left hand. The patient was referred for surgical treatment of her hyperparathyroidism. Histological examination of the lesion was compatible with a benign parathyroid adenoma. Over repeated follow-up visits, she remained in an excellent physical condition without any evidence of neurological deficit within 2 months of intensive physiotherapy program. Case 2 (Pulmonary Embolism) A 44-year-old, female patient presented to the Emergency Department with acute-onset, right-side chest pain, accompanied by fatigue and dizziness. Her medical history was remarkable only for recurrent episodes of renal colic. She denied smoking, frequent alcohol intake or therapy with any medication. Physical examination on presentation did not reveal any abnormal findings. Her blood pressure was 130/80mmHg, the heart pulse 80 /min, the respiratory rate 22/min, while the temperature was 35.9 °C. The oxygen saturation was 96% and the ECG demonstrated sinus rhythm. Laboratory evaluation revealed elevated d-dimers (4021 ng/ml, normal < 500) and serum calcium levels (15.04 mg/dl, 8.8-10.5). The aforementioned combination of clinical symptoms and laboratory findings raised the suspicion of Pulmonary Embolism (PE) and an urgent spiral CT angiography was ordered, which demonstrated a small filling defect in the hilum of the right lung. Low molecular weight heparin (LMWH) was administered for the treatment of PE, as well as intravenous hydration and calcitonin for the management of hypercalcemia. Further laboratory tests were ordered in order to identify the cause of hypercalcemia. PTH was measured excessively high (72.1 pmol/l, 1.58-6.03), while the 24-h urine calcium was respectively elevated (604 mg/24h, 100-250). Phosphorus (1.5mg/dl, 2.7-4.5) and 25(ΟΗ)D3 (18.2 ng/ml, 30-100) were found below the normal limits (). Ultrasonography was suggestive of an adenoma, sized 0.6 x 0.8 x 2.23 cm of the left inferior parathyroid gland. This finding was also confirmed by Tc99m Sestamibi imaging. Skeletal radiograph illustrated subperiosteal resorption of the phalanges, and renal ultrasound demonstrated a large coralloid renal stone in the left kidney. Bone densitometry (DXA scan) was indicative of osteoporosis (L1-L4 lumbar vertebras T-score -3.6, left neck femur T-score -2.8, right neck femur -3.8). The assessment for blood coagulation abnormalities revealed high homocysteine levels (45.2 μmol/lt, normal <15) and homozygosity for Methylene tetrahydrofolate reductase (MTHFR) C677T mutation. No signs of DVT or findings suggestive of malignancy were found in imaging. After recovering from PE, the patient was referred for parathyroidectomy, and histological examination of the lesion was compatible with parathyroid adenoma. Following surgery, PTH and calcium levels returned to normal and the patient remained in good physical condition during her follow-up over a period of 6 months. Case 3 (Deep Venous Thrombosis) A 58-year-old female was referred by her General Practitioner to the Emergency Department due to lower right leg edema for 3 days. She had a history of Hashimoto thyroiditis and generalized arthralgia under investigation. She was on levothyroxine 125 mcg once daily. On presentation, the patient had a low-grade fever (37.5 o C), but was hemodynamically stable. Physical examination revealed tenderness, erythema, elevated temperature and edema in her right calf, while Homans sign (pain on dorsiflexion of the foot) was positive. Initial laboratory evaluation demonstrated abnormal d-dimers (3018 ng/ml, normal < 500) and serum calcium levels (15.1 mg/dl, 8.8-10.5). Triplex venous ultrasonography of the lower limbs was suggestive for extended DVT in the right leg. The patient was treated with LMWH, intravenous administration of saline, calcitonin and zolendronic acid. Additional investigation of hypercalcemia brought to light findings compatible with the diagnosis of PHPT [PTH 79.3 pmol/l, 24h calcium urine excretion 304 mg/24h, 25(ΟΗ)D3 7.1 ng/ml and phosphorus 2.6 mg/dl] (). Parathyroid sestamibi scintigraphy was indicative for an adenoma in the left lower parathyroid gland. CT scans of the thorax and abdomen, as well as mammography were negative for malignancy. The combination of long-term arthralgia and DVT raised the suspicion of an underlying autoimmune disorder. Multiple autoantibodies, including antiphospholipid, anti-cyclic citrullinated peptide (anti-CCP), anti-neutrophil cytoplasmic (ANCAs), antinuclear (ANA) and anti-double stranded DNA (anti-dsDNA) were measured, but were all negative. In the end, a lip biopsy confirmed the diagnosis of primary Sjogren’s Syndrome (SS). The patient was subjected to parathyroidectomy, and histological examination of the removed lesion revealed a benign parathyroid adenoma. After surgery, both calcium and PTH levels returned to normal. She remains under the care of the rheumatology team for monitoring recently diagnosed SS.
pmc-6305264-1	A 38-year-old female (gravid 3, Para 3) with performance status of 1 had a 20-day complaint of irregular vaginal bleeding. A biopsy of the anterior vaginal fornix revealed small cell endocrine tumour. The patient was then referred to our center for further management. The patient was first seen by our specialist gynec onco surgeon. On examination, she was in perfect physical condition, without any history of weight loss, fever, or night sweats. Pelvic examination suggested polypoid tumor mass, 4.5 X 4 X 2 cm, arising from lateral fornix of right side of vagina. Biopsy material showed chloroma. LCA, MPO (myeloperoxidase) and c-kit were positive on IHC (immunohistochemistry), while negative for cytokeratin, synaptophysin, chromogranin, CD20, CD99 and CD79a. Complete hemogram with peripheral smear, renal and liver function test, blood sugar, lactose dehydrogenase, uric acid were normal. There was no palpable organomegaly and lymphadenopathy. Contrast enhanced Computer Tomography scan of thorax, abdomen and pelvis showed 5 x 5 cm mass lesion lateral to cervix, supra diaphragmatic lymphadenopathy, infra diaphragmatic lymphadenopathy, mild hepatomegaly, and splenomegaly. Bone marrow aspiration, trephine biopsy, conventional cytogenetic analysis and 2D echo were also normal. Disease diagnosis and chemotherapy side effects were explained to the patient. After written consent, the patient received induction chemotherapy with the “3+7” regimen, including daunorubicin and cytarabine. The patient showed a partial response after completion of chemotherapy, and then she was consolidated with high-dose cytarabine and local radiotherapy. She was asymptomatic and was kept under regular surveillance for 12 months at our institution.
pmc-6305270-1	We present a 61-year-old immunocompetent woman. A month prior to her hospital admission, she had an episode of confusion with numbness in the right leg and arm, slurred and dysarthric speech. She reported urine incontinence during the night that had occurred once during the past month. There was no data for lymphoma in the family. Peripheral blood tests were normal. The neurological examination demonstrated a latent hemi-paresis of the right side, aphasia, discrete hypertension and bradypsychia. The ophthalmologic examination revealed left quadranopsia. Computed tomography and magnetic resonance imaging of the brain showed a 3.5 × 2.9 cm infiltrative neoplastic lesion involving the left temporal parenchyma (). Based on clinical and MRI data, the patient underwent left frontо-temporal craniotomy with partial excision and verification of the tumor. The lesion was surgically excised under sonographic control in the conditions of intra-operative contrast enhancement with Fluorescein Na. After the operation, the patient demonstrated satisfactory state with persistent bradypsychia and discrete aphasia. The patient was administered on Depaquin 0.5 mg daily and recovered well after the surgical intervention. Histological examination of the resected tumor described lymphoid tumor cells with small oval hyperchromic nucleus, condensed chromatin and scarce cytoplasm. The tumor cells were located in the peri-vascular spaces, arranged in concentric pattern among layers of reticulin-positive (Gomory +) material around blood vessels. There were significant reactive changes in the adjacent brain tissue. The neoplastic lymphoid cells were positive for CD45, CD20 and Bcl-2, whereas they were negative for CD5, CD10, CD23, Bcl-6, and Cyclin D1 as determined by immunohistochemistry, with a very low proliferation rate of 1% revealed by Ki-67, admixed with numerous reactive CD3+CD5+ T cells. The morphological features and immunophenotyping of lymphoid composition were consistent with low-grade (indolent) B-lymphocyte non-Hodgkin’s lymphoma of CNS. After determination of the stage of the disease, chemotherapy was administered, but the patient acquired pneumonia and died after ten months.
pmc-6305339-1	A 64-year-old woman was admitted to our hospital with a pulsatile mass swelling over the left cervical region and right hemiparesis after cough for 1 day. She had a history of fibromatosis, but no previous history of trauma, operation or inflammation in this region. On physical examination, a 5-cm large pulsatile swelling with blowing bruit was found over the left cervical region and multiple fibromas were found in regions of face, neck, and trunk. Neurological examination revealed muscular strength of grade IV according to the ‘manual muscle test (MMT)' grading system and hypoesthesia of right limbs, including touch and pain sensation. Computed tomography angiography (CTA) and DSA revealed a left high-flow internal carotid-jugular fistula at the first cervical level and twisted left internal carotid artery (ICA) (Figures ). Blood flow from the vertebrobasilar artery and right ICA via the circle of Willis supplied the left anterior cerebral artery and middle cerebral artery and drained backwards into the petrosal segment of left ICA (Figures ). We chose embolization of both the fistula and parental artery, because no appropriate covered stent could be used to pack the fistula in the condition of reservation of left ICA. The purpose of first endovascular treatment was to isolate the fistula, by blocking both the backward blood flow from right ICA and the forward blood flow from left ICA. A Headway-21 stent catheter was selectively inserted into the distal part of fistula in the segment of carotid cavernous sinus, meanwhile an Echelon-10 microcatheter was placed in the distal part of stent catheter. One LVIS 5.5*30 mm stent, with its characteristic relatively compact mesh, was used to cover the distal part of fistula to avoid coils being pushed into internal jugular vein and heart (Figure ). However, the 3.5 cm fistula could not be covered by the LVIS stent. Therefore, 10 coils were additionally used one by one, to block the fistula from the distal to proximal part through an Echelon-10 microcatheter (Figure ). When considering the fast-backward blood flow from the right ICA after embolization, we could not guarantee the safety of blocking by Onyx. We chose one detachable balloon to block the ICA near the proximal part of fistula to stop the forward blood flow, and the backward blood flow would be stopped in the second treatment (Figures ). The blowing bruit was reduced significantly after the first treatment, but became worse after 2 months later. The patient was admitted to our hospital again, and DSA revealed residual blood flow in the fistula from the left ICA and premature balloon deflation (Figures ). It was fortunate that LVIS stent blocked the balloon into the internal jugular vein. An additional 13 coils were used to pack the fistula with double-microcatheter techniques, under the multi-angle DSA projection, to avoid the coil protruding into the internal jugular vein (Figures ). Afterwards, two detachable balloons were used to block the proximal part of left ICA again (Figure ). DSA revealed the forward blood flow disappeared, the low-flow backward blood from right ICA still supplied the fistula, and a normal ipsilateral jugular vein (Figure ). Because the fistula was mostly blocked, and the low-flow backward blood may promote the formation of thrombosis in the distal part of fistula, we stopped the second endovascular treatment and planed a DSA examination to evaluate the effect of embolization and to determine further treatment. After this treatment, the patient did not feel the blowing bruit or any other discomfort. However, the patient complained of swelling and pain in the left occipitocervical region 2 days later. Physical examination revealed a large subcutaneous mass, with volatility and severe tenderness. Emergent CT revealed a subcutaneous hematoma in left occipitocervical region, without abnormalities in brain (Figures ). DSA in the hybrid operation room showed the coils in the fistula were stable without no forward blood flow in the proximal part of fistula. However, there was still a little backward blood flow through the right ICA and vertebrobasilar artery into right internal jugular vein, via the distal part of fistula. The lower part of fistula was not shown, because the blood drained into the right internal jugular vein through the sigmoid and transverse sinus reversely (Figures ). It was suggested that the occipitocervical subcutaneous hemorrhage was caused by poor ipsilateral jugular drainage, which was the result of the formation of thrombosis in fistula extending to the left internal jugular vein, thus blocking forward and backward reflow. We inserted an Echelon microcatheter through the left vertebrobasilar artery-posterior communicating artery, then selectively to petrosal segment of the left ICA, where 3 coils were put in, and then a 1.2 ml Onyx-18 was injected slowly. DSA examination after this procedure revealed that the backward blood flow distal to the fistula disappeared (Figures ). An open operation to remove the hematoma was preformed after the interventional operation. Multiple capillary hemorrhages were found from behind the sternocleidomastoid muscle after removing clots. The operation to stop bleeding was successful, and the postoperative course was uneventful. A 6-month follow-up DSA demonstrated a totally occluded fistula allowing the patient to engage in light manual labor with normal neurological functioning after the operation (Figures ).
pmc-6305431-1	The participant was a 32-year-old man with a well-documented history of autonomic dysfunction () including autonomic dysreflexia as well as neurogenic lower urinary tract and bowel dysfunction as a consequence of his motor-complete, sensory incomplete SCI (C5, American Spinal Injury Association Impairment Scale B) () sustained in a diving accident in 2012. The participant was relying on intermittent catheterization to empty his bladder and suppository use as well as digital stimulation to facilitate bowel routine. With the intent to improve his motor function, the participant received an ESCS unit and 16-electrode array (RestoreAdvanced SureScan MRI neurostimulator, Specify 5-6-5, Medtronic, Minneapolis, MN, United States) in 2016. The neurostimulator was equipped with numerous pre-set stimulation programs comprising different electrode configurations and stimulation parameters (i.e., frequency, pulse width and intensity). Compared to no stimulation (Panel A), we applied a variety of pre-set stimulation programs (Panels B to H) during our assessments. Each stimulation program was designed to activate specific groups of skeletal muscles responsible for: (Panel B) left ankle dorsiflexion and left hip/knee flexion, (Panel C) left hip/knee flexion, (Panel D) left knee extension, (Panel E) right knee extension, (Panel F) right step forward, (Panel G) right ankle dorsiflexion and right hip/knee flexion, and (Panel H) bilateral trunk muscle activation. The participant utilizes the stimulator as needed by simply turning it on and selecting a program. In contrast to frequency and pulse width, which were pre-set, the participant can change the intensity of each program manually as needed. Prior to our investigation, a radiologist confirmed correct placement of the 16-electrode array at vertebral levels T11 to L1 via conventional radiography (Figure ). Urodynamic investigation along with surface external anal sphincter/pelvic floor electromyography is the gold standard to assess lower urinary tract function (). First, baseline urodynamic investigation (Aquarius TT, Laborie Model 94-R03-BT, Montreal, QC, Canada) was performed in accordance with the International Continence Society’s ‘Good Urodynamic Practices’ () to evaluate the current extent of neurogenic lower urinary tract dysfunction. Since the participant is not able to void spontaneously, we only conducted an experimental urodynamic investigation to evaluate if ESCS of the lumbosacral spinal cord exerts an acute effect on detrusor pressure, as well as external anal sphincter and pelvic floor muscle tone during the storage phase. For this, we prefilled the bladder to a volume of 250 mL (i.e., 60% of maximum cystometric capacity from the first urodynamic investigation), without eliciting neurogenic detrusor overactivity or autonomic dysreflexia. Then, pre-set stimulation programs (B to F) were applied for at least 90 s each. Concurrent to the urodynamic investigation, we continuously recorded beat-by-beat blood pressure, via finger photoplethysmography (Finometer PRO, Finapres Medical Systems, Amsterdam, Netherlands) corrected to brachial pressure (CARESCAPE V100, GE Healthcare, Milwaukee, WI, United States), and one-lead electrocardiogram (eML 132; ADInstruments, Colorado Springs, CO, United States) for heart rate in order to detect autonomic dysreflexia (). Autonomic dysreflexia is defined as a response to noxious or non-noxious stimuli below the level of SCI that typically occurs primarily in people with an SCI at or above the T6 spinal segment. This condition is characterized by an increase in systolic blood pressure of 20 mmHg or more above baseline (). Autonomic dysreflexia is highly prevalent in this population () and can occur more than 40 times per day (). As blood pressure can rise above 300 mmHg, autonomic dysreflexia is a potentially life-threatening condition that can result in stroke, seizure, myocardial ischemia, or even death (). Prior to the urodynamic investigation, baseline measurement of brachial blood pressure and heart rate was performed three times within 5 min and averaged. All lower urinary tract assessments were performed in the supine position. To assess the magnitude of bowel dysfunction in individuals following SCI, ‘The Neurogenic Bowel Dysfunction (NBD) Score’ questionnaire has been shown to provide a clinically meaningful outcome measure with a good reproducibility and validity (). This standardized questionnaire comprises 10 questions focusing on defecation (i.e., frequency, duration, and clinical symptoms), constipation (i.e., use of aiding medication and digital stimulation), fecal incontinence (i.e., frequency, aiding medication, and flatus) and peri-anal skin problems. The consequential NBD score relates to four different neurogenic bowel dysfunction severity levels (i.e., score 0–6 = very minor, 7–9 = minor, 10–13 = moderate, and 14–47 = severe). In addition to the NBD score, the questionnaire assesses the patient’s general satisfaction regarding current bowel function through one item (i.e., a numeric rating scale: from 0 = total dissatisfaction to 10 = total satisfaction). We next objectively tested various stimulation programs compared to conventional bowel routine (i.e., suppository use only) in terms of time required for bowel management. In a randomized order, three different stimulation programs (Panels E, G, and H) representing different electrode configurations and stimulation parameters as well as conventional bowel routine (Panel A) were each assessed three times (i.e., overall 12 trials) within a period of 1 month. To assess and compare the time required for bowel management, the participant was instructed to record the time from ‘suppository insertion’ to ‘when bowel evacuation was completed’ at his home. The neurostimulator was turned on after the suppository insertion and turned off following completion of bowel evacuation. Depending on electrode configuration and stimulation parameters (i.e., amplitude, frequency, and pulse width), ESCS modulated lower urinary tract (Figure ) and bowel function (Figure ) to various degrees. Epidural spinal cord stimulation applied to caudal parts of the array increased external anal sphincter/pelvic floor muscle tone and detrusor pressure, while configurations stimulating the rostral part of the array had more modest or no effects compared to baseline. Blood pressure and heart rate remained stable during ESCS and autonomic dysreflexia did not occur. Compared to conventional bowel routine (i.e., suppository alone), ESCS (plus suppository) significantly expedited bowel management (p = 0.039). On average, ESCS reduced the time required for bowel routine by more than 55% (i.e., 26 vs. 58 min). Furthermore, ESCS decreased the severity of neurogenic bowel dysfunction from severe to minor as evidenced by a reduction in NDB Score from 15 to 8, as well as improved the general satisfaction scale from 5 to 8.
pmc-6305442-1	Patient A was a 15-year old male referred for immunological investigation because of IgM deficiency, subtle hypogammaglobulinemia, recurrent stomatitis aphthosa and recurrent respiratory tract infections such as sinusitis and bronchitis (Table ). He suffered from pneumonia at the age of 6, but otherwise had an uneventful medical history. He was the child of healthy unrelated parents of Austrian origin, a healthy brother was 10 years old. Upon initiation of antibiotic prophylaxis with amoxicillin (50% therapeutic dose daily) and pneumococcal vaccination susceptibility to respiratory infections normalized.
pmc-6305442-2	Patient B was a 37-year old male of Turkish descent referred for immunological investigation by the treating nephrologists because of IgM deficiency. Asymptomatic renal insufficiency was detected at the age of 28 years when a cirrhosis of the left kidney and mild hydronephrosis of the right kidney were found. Serum creatinine was 3.2 mg/dl (normal range 0.6–1.2 mg/dl), proteinuria was 2.5 g/d. He reported no increased susceptibility to infections, and his chronic renal insufficiency caused only mild clinical symptoms (development of fatigue and tachycardia upon physical strain). The mRNAs encoding the membrane-bound and secreted immunoglobulin heavy chains are produced from identical primary transcripts, which are differently processed at their 3′ ends. Regulation of membrane-bound vs. secreted forms of the immunoglobulin heavy chains depends on the competition of 2 mutual cleavage polyadenylation sites (pAs/pAm) (). In mice targeted deletion of the mu heavy chain cleavage polyadenylation site pAs leads to deficiency of secreted IgM with intact expression of surface IgM and normal secretion of other immunoglobulin isotypes (). Therefore, we sequenced mu heavy chain gene including the polyadenylation sites in both patients with sIgMD and found no alterations (data not shown). Both patients' B cells were able to express precursor, secreted and membrane IgM mRNA (Figure ). Furthermore protein expression of monomeric and native pentameric IgM (Figure ) and surface expression of IgM on the B cell membrane (data not shown) was comparable to healthy controls. To elucidate the genetic basis of the patients' selective IgM deficiency we used a targeted resequencing approach to sequence potential candidate genes. In both patients, we identified defects within the intrinsic B-cell receptor signaling pathway. Patient A harbored a c615G > T missense mutation in exon 8 in the tyrosine kinase BTK. The G > T transition resulted in a glutamic acid to aspartic acid substitution at position 205 within the highly conserved proline-rich (PRR) region located at the C-terminus of the TEC homology (TH) domain (Figures ). Proline rich regions are involved in protein-protein interactions, including interactions with G proteins and intramolecular association with the SH3 domain (). Mutations within the proline rich regions have been shown to abolish SH3 domain binding and result in functional impairment of BTK, pointing toward a potential biologic relevance of the BTK mutation found in patient A ().
pmc-6305567-1	A 78-year-old Japanese woman who complained of blurred vision in her right eye visited an ophthalmology clinic. Because RRD was suspected, she was referred to a nearby vitreoretinal surgery center. When RRD with choroidal elevation was noted in the center, the ophthalmologist evaluated CD as atypical. She was eventually referred to our hospital in June 2015. Her medical history revealed nothing of note. Ophthalmological findings demonstrated visual acuity of 4/20 in the right eye (OD) and 10/20 in the left eye (OS). The patient’s intraocular pressure was 12 mmHg OD and 16 mmHg OS. Slit-lamp examination demonstrated clear anterior chambers and senile cortical cataracts in both eyes. Mild pigmented anterior vitreous cells were noted OD. Fundus examination displayed retinal detachment involving the inferior and nasal retina, where a round retinal hole was noted OD (Fig. a, arrow). A yellowish flat choroidal elevation was located nasally from the retinal hole. Optical coherence tomography displayed mild subretinal fluid in the macula OD. Fluorescein angiography (FA) revealed hyperfluorescence corresponding to retinal detachment without nonperfusion areas in the fundus (Fig. b). Indocyanine green angiography (IA) demonstrated hypofluorescence in the nasal quadrant corresponding to the location of tumor and/or RRD (Fig. c). B-mode echography revealed mild choroidal elevation OD with the height of the tumor less than 2 mm. Magnetic resonance imaging (MRI) displayed marginally high and low intensities with T1 and T2 weighting in the choroidal tumor, whereas relatively low intensities and isointensities were detected in the retinal detachment compared with those in the tumor, respectively (Fig. a, b; arrows). The choroidal tumor was enhanced by gadolinium (Gd) (Fig. c, arrow). The patient was clinically diagnosed with CM complicating RRD. Systemic imaging modalities did not show abnormalities, except in her right eye. She underwent linear accelerator radiation therapy by X-ray (total dosage, 70 Gy) in a nearby hospital because she refused enucleation and other possible treatments. However, because she had severe ocular pain due to a persistent corneal ulcer, she eventually underwent enucleation in October 2015. Histological findings demonstrated typical mixed-type malignant melanoma with a low Ki-67-positive rate. However, liver metastasis developed about 1½ years after the enucleation. The patient was fine without systemic treatments based on her will in December 2017, and she is being observed in a nearby palliative care center.
pmc-6305571-1	A 71-year-old Caucasian woman with known diverticular disease of the colon and MM diagnosed 3 years previously, who was receiving chemotherapy with melphalan, bortezomib (a proteasome inhibitor), and a moderate dose of dexamethasone, presented to the emergency department of our hospital with abdominal pain, abdominal discomfort, and pneumoperitoneum. The clinical examination revealed acute abdomen with free air on an abdominal plain x-ray, and elevated levels of leukocyte cells at 18,000/μl and C-reactive protein at 145 mg/L. The patient had a family history free of cancer, and the last time she underwent colonoscopy was 1 year before admission. She had been diagnosed 3 years previously with stage II MM based on the International Staging System with a β2-microglobulin level of 4.2 mg/L and serum albumin level of 37 g/L. No study was performed for amyloidosis. An abdominal CT scan showed a 5-cm-wide, 12-cm-long sigmoid mass with medial extension into the fatty tissue at the same localization, pneumoperitoneum, diverticula, free abdominal fluid collections, and distended loops of the small and large intestines (Figs. and ). The patient was urgently admitted to the operating room as soon as the diagnosis of colonic perforation was established. An exploratory laparotomy was performed, with supra- and subumbilical midline incisions. Intraoperative findings were purulent peritonitis and an obstructive mass of the sigmoid colon causing massive central colonic distention (Figs. and ). The mass was extending toward the mesosigmoid. It was impossible to define if the mass might be originating from the mesocolon (Fig. ). After washing the whole abdomen meticulously, exploration revealed colonic perforation in the midtransverse colon at the mesocolic site. The mesocolon at this part was extremely inflammatory and had signs of venous congestion. An extended left colectomy was decided as the operation of choice for this patient. The operation was undertaken in an ontological fashion, with high ligation of the superior mesenteric artery and retrieval of all regional and apical lymph nodes. Peripheral transection was performed at the level of the upper rectum, and after removal of the specimen, a transverse stoma was established (a modified Hartmann’s procedure). Direct anastomosis was considered extremely risky owing to local inflammatory conditions (after peritonitis) and a highly distended colon (after obstruction). The histopathologic study of the lesion showed large oval cells consisting of a round nucleus in eccentric position with coarse chromatin, protruding nucleolus, and enough cytoplasm (Fig. ). There were also a few cells with double nuclei as well as giant nuclei. Few cells had the morphology of typical plasmacytes. There were many mitoses. Higher cell apoptosis was observed in the largest part of the tumor. The neoplasm densely infiltrated the muscular wall of the intestine and the pericolic fat without reaching the surface of the serum and without infiltrating the mucosa, which had severe ischemic lesions (Fig. ). The surgical margins were free. In IHC analysis, the tumor cells were CD20−, CD5−, CD79a+, CD138+ (moderate), CD38+ (moderate), CD56+, CD10−, CD30−, CD117+ (a few), keratins AE1/AE3−, and S-100− (Fig. ). IHC analysis for both kappa-light and lambda-light chains gave an unreliable effect owing to a very high substrate material (Fig. ). The Ki-67 cell proliferation index was approximately 40%. In the lymph nodes, morphologically and with CD138 and CD38 immunostaining in selected sections, infiltration by the neoplastic cell population was not documented. The patient did well postoperatively.
pmc-6305730-1	Patient 3 was 35 to 40-years old, he was unemployed and reported he was not able to continue his job because of drinking problems. He also reported that difficulties surrounding alcohol use started to become serious 12 years prior, with binge drinking episodes pre-dating this time. During last 10 years he began using alcohol when alone, and on a daily basis, and this habit gradually led to a reduction of social contacts and general withdrawal. He also met criteria for Major Depressive Disorder.
pmc-6305815-1	Patient 1, a seven-year-old boy, who belonged to a consanguineous couple, was born by normal delivery. His mother experienced pregnancy with intrauterine fetal death. Initial symptoms arisen in him since birth included muscle weakness, inactivity, and hypotonia. At the age of ten months, concentrations of lactate dehydrogenase, CK, and aldolase were found to be 2005 IU/l (normal range 180–430 U/L), 1248 U/l (normal range 200-400 U/l), and 13.9 IU/l, respectively. Electromyography (EMG) results showed low amplitude and duration of the motor unit action potential (MUAP). The CK and aldolase levels were measured to be 2136 U/l and 12 U/l, respectively, when the patient was two years old. The MRI of the brain was normal at one year of age, and there was no history of seizure. At the age of two years and six months, immunohistochemical (IHC) analysis results showed weak and patchy sarcolemmal labeling with merosin antibody. Muscle biopsy results showed severe myopathic atrophy with endomysial fibrosis, compatible with muscular dystrophy. At age seven, he had kyphosis, short elbow, and contractures of elbow and wrist. The CK and aldolase levels decreased to 523 U/l and 5.5 U/l, respectively (). He attended a regular school having normal intelligence (with IQ score estimated to be 160). Based on clinical and biochemical finding, MDC1A was proposed.
pmc-6305815-2	Patient 2 was a five-year-old boy who was delivered via caesarean section at full-term and belonged to a non-consanguineous marriage. At the time of birth, the child manifested hypotonia and a myopathic face. There was no history of CMD in the family. At the age of five months, the concentrations of lactate dehydrogenase, CK, and aldolase were found to be 871, 1762, and 21 U/l, respectively. Motor and sensory nerve conduction results were normal with no evidence of peripheral neuropathy. The EMG results showed moderate positive sharp waves, fibrillation, low amplitude, and duration of motor unit activities. The EMG, motor, and sensory conduction analyses proposed a diagnosis of the spinal muscular atrophy, and due to the short duration and low amplitude of the motor unit, occurrence of congenital myopathy was not ruled out in this case. At age three, the genetic test result was negative for SMN1 gene using the multiplex ligation-dependent probe amplification method. At age four, the result of muscle biopsy analysis was compatible with the muscular dystrophy, and the IHC study of the sarcolemmal proteins showed a loss of labeling of all muscle fibers and nerve bundles with merosin antibody (). At age five, clinical examination showed kyphoscoliosis and contracture of elbow and wrist. Considering the results, a genetic study of the LAMA2 gene was suggested.
pmc-6305815-3	Patient 3 was a six-year-old boy born into healthy consanguineous parents. He showed hypotonia since birth. The CK and aldolase were found to be 6304 and 44 U/l, respectively. At the age of five months, the result of muscle biopsy and IHC tests demonstrated dystrophic changes. Then MRI study of the brain was suggested for the patient in which was normal at the age of six months. Based on clinical and biochemical finding, merosin deficiency was proposed, and genetic test for the LAMA2 gene was recommended. At the age of six, he had kyphosis, and cognitive function was normal with no history of seizure ().
pmc-6305880-1	Patient A was a 56-year-old woman. She was diagnosed with recurrent depressive disorder and fibromyalgia. She was prescribed a daily oral medication of duloxetine 90 mg, quetiapine 150 mg, pregabalin 300 mg, and zolpidem 10 mg. She had regular bedtime and wake-up times during the study period. The clinical assessment of depression showed high scores of PHQ-9: 21 on April 6, 2017, and 25 on May 31, 2017. Unfortunately, this woman dropped out of medical follow-up, and there are no more clinical assessments. She participated in the study from April 6, 2017 to February 28, 2018 and owned a Samsung Galaxy S7 that ran Android 6.0.1. shows that the MDL criterion selected 8 different clusters (ie, types of days or mobility patterns). We plotted the patient’s inferred mobility patterns (in logarithmic scale), which are given by the mean of each cluster. For instance, profile 5 corresponded to a more active day and, on the days associated with this profile, the patient was more active between 9:00 and 16:00. Moreover, some of these profiles reported similar activity variations throughout the day. The sleep period was identified by a decrease in the activity between 1:00 and 6:00. shows the output of the second step of the proposed method, the change-point detector; this figure displays the dates of the change-points (top) and the classification of each day given by the clustering technique and its temporal evolution (bottom). The algorithm identified a few dates as mobility pattern changes. Concretely, changes were noted on April 26, May 31, August 19, September 3, October 27, and November 5. These changes appeared when the probability (a portion of time) of each type of day varied. Finally, we must point out that in , where the temporal evolution of the types of days is shown, vertical light-blue rectangles indicate that the data corresponding to the marked days were completely missing. Even in these cases, the technique was robust enough to work properly.
pmc-6305880-2	Patient B was a 45-year-old woman. She was diagnosed with dysthymia and prescribed a daily oral medication of sertraline 100 mg. The clinical assessment of depression showed clinical improvement of depressive symptoms (June 7, 2017: PHQ-9=20; July 5, 2017: PHQ-9=8). Overall, medical records showed improvement during follow-up, explained by the participant as an improvement in cognitive performance, a decrease of death thoughts, and improvement of hedonic capacity. She participated in the study from June 7, 2017 to January 30, 2018, and owned a Samsung Galaxy A5 running Android 6.0.1. In this case, the technique selected 5 different clusters. shows the patient’s average mobility patterns. shows that our technique did not identify any change and that profile 4 was the most common, which was a low-mobility profile (there was not a single hour with >1 km). In this particular patient, clinical changes did not correlate with mobility as the main symptoms were expressed in cognitive and hedonic areas.
pmc-6305880-3	Patient C was a 40-year-old woman. She was diagnosed with a moderate depressive episode. She was prescribed a daily oral medication of paroxetine 20 mg, which was changed to vortioxetine 10 mg in August owing to the lack of improvement. Medical records showed an improvement after the change to vortioxetine. This patient participated in the study from June 9, 2017 to February 28, 2018, and owned a Samsung Galaxy A5 that ran Android 7.0. In this case, the technique only considered 4 different types of days. shows the average distance traveled in each cluster, where we observed that the patient was more active after 7:00 in 3 out of the 4 profiles. Moreover, the remaining profile, profile 2, showed increased activity during the night, and profile 4 corresponded to a low-mobility profile. shows that the change-point detection algorithm detected only one change on December 9; after this date, the low-mobility profile began appearing more often, which possibly indicated a decrease of the patient’s physical activity. The clinical assessment of depression showed a decrease in depressive symptoms during the follow-up period (June 9, 2017: PHQ-9=22; Sept 9, 2017: PHQ-9=5; December 1, 2017: PHQ-9=4). Clinical improvement was associated with improved sleep time and sleep quality. A change of her work location led to less commuting, which can also explain the observed mobility patterns.
pmc-6305880-4	Patient D was a 36-year-old man. He was diagnosed with recurrent depressive disorder and prescribed a daily oral medication of venlafaxine retard 150 mg and lamotrigine 100 mg. He was included in the study after psychiatric hospitalization discharge, and clinical and functional remissions were observed in successive appointments in the outpatient setting. The clinical assessment of depression showed minor clinical improvement (March 17, 2017: PHQ-9=6; April 20, 2017: PHQ-9=2; May 24, 2017: PHQ-9=2; and June 26, 2017: PHQ-9=0). He participated in the study from April 6, 2017 to August 11, 2017, and owned a Samsung Galaxy J7 running Android 6.0.1. shows that the number of profiles selected by the MDL criterion was 4. Profiles 1, 3, and 4 corresponded to typical urban mobility profiles. Some showed higher mobility during day or night, and some had peaks at commuting times (7:00 and 19:00). However, profile 2 corresponded very likely to a trip as the average movement per hour was around 100 km. shows the results of the change-point detector, which did not detect any change-point; this is coherent with the clinical evolution of the patient.
pmc-6305880-5	Patient E was a 42-year-old woman diagnosed with adjustment disorder with depressed mood and lumbar stenosis. She was prescribed a daily oral medication of escitalopram 15 mg, pregabalin 150 mg, and ketazolam 15 mg, besides antialgic medication. Fluctuations in the mood level were observed during follow-up in relation to back pain exacerbation. This patient participated in the study from October 11, 2017 to December 21, 2017, and owned a BQ Aquaris M5 that ran Android 6.0.1. In addition, this patient showed improvement in depression scores during the study (June 23, 2017: PHQ-9=10; October 5, 2017: PHQ-9=6). In this case, as shows, the MDL criterion only selected 3 profiles, as the amount of data was rather small and, otherwise, would very likely have resulted in overfitting. Overall, 2 profiles corresponded to activity during the daytime, whereas profile 2 showed activity evenly distributed during the whole day. shows that the technique identified one change-point on November 25, 2017. Interestingly, this change-point appeared when profile 2 disappeared. The change-point coincided with an increase of painful osteoarticular symptoms.
pmc-6305950-1	A 54-year-old female presented to our medical center with a 2-month history of progressive dysphagia and odynophagia. The patient experienced a sensation of solid foods “getting hung up” in her neck. However, she did not report choking or gagging. Before her current presentation, she underwent neck ultrasonography at the office of her primary care physician, which revealed a 6.1-cm complicated cyst. Considering it an infectious etiology, she was empirically treated with antibiotics, but her symptoms persisted. Her past medical history was significant for hypertension. She had no other complaints and there was no history of immunosuppressive disorders like HIV/AIDS, celiac disease, or inflammatory bowel disease. She denied nausea, vomiting, fever, chills, gastroesophageal reflux symptoms, or weight loss. Family history was negative for cancer. Physical examination was significant for a large, tender, and palpable neck mass. Laboratory studies for hematology, serum biochemistry, and urine analysis were within normal limits. Computed tomography (CT) scan of the head and neck showed a 7.3 × 3.1 × 6.6-cm mass in the neck, which was inseparable from the cervical esophagus (). It was located adjacent to the vertebral body without apparent bone compression (). Barium esophagogram showed an intact esophageal mucosa, with marked narrowing of the cervical part of the esophagus. Esophagogastroduodenoscopy confirmed the tumor-related esophageal luminal narrowing. EUS-guided FNA was performed, which came out inconclusive. Subsequently, the interventional radiology team performed an uneventful biopsy of the neck mass. Histopathologic analysis of the biopsy specimen showed relatively large malignant lymphocytes with a moderately abundant cytoplasm and round-to-ovoid nuclei having prominent nucleoli and occasional mitoses (). Immunohistochemical examination yielded positive results for CD20 and CD10 antibodies, whereas staining was diffusely positive for BCL6 antibody (). On the basis of these pathologic findings, the patient was diagnosed with primary esophageal DLBCL. The lesion was classified as high grade due to a very high Ki-67 proliferative index (). A whole-body gallium scan was negative for other abnormalities. Bone marrow biopsy ruled out malignant changes. According to Ann Arbor staging, this was a stage IEA DLBCL with isolated esophageal involvement. The patient was initiated on chemotherapy with R-CHOP regimen. She received a total of 4 chemotherapeutic cycles followed by radiotherapy. She tolerated the treatment well without serious adverse events. The clinical response was good with resolution of dysphagia achieving complete remission in 3 months. During the 3-year follow-up period, the patient did not experience a recurrence of the lesion. She continues to do well to date.
pmc-6305996-1	We present a case of a 28-year-old white man with an 8-month history of clinical symptoms of anemia, such as fatigue and breathlessness, without any abdominal complaint. He had autoimmune hemolytic anemia treated by corticosteroids for more than 6 months but with a relapse of disease after steroid remission. For this reason, he was a candidate for a splenectomy. His occupation is a student. He did not smoke tobacco or consume alcohol, and he was taking prednisone, bisphosphonates, vitamin D, and calcium. No other immune disorders were found. On admission, his blood pressure was 90/70 mmhg, his heart rate was 70 beats/minute, and his body temperature was 36 °C. Physical examination of the patient revealed a severe pale conjunctiva and icteric sclera with no evidence of abdominal mass or other physical abnormalities. Laboratory analysis results on admission are shown in Table . Abdominal computed tomography (CT) performed before the splenectomy showed a large cystic mass between the stomach and the spleen with no evidence of communication with the stomach or pancreas. Endoscopic ultrasound (EUS) showed a cystic mass located along the greater curvature with no mucosal abnormality or communication with the gastric lumen. Magnetic resonance imaging performed for more characterization showed a cystic mass between the stomach and spleen with a high signal intensity on T2-weighted fat-saturated magnetic resonance images (Fig. ) and peripheral enhancement after gadolinium injection (Fig. ). At this stage, the differential diagnoses included hydatid cyst, mesenteric cyst, and pancreatic pseudocyst. The patient underwent exploratory laparotomy with complete cyst resection and splenectomy. At gross examination, the cystic mass, measuring 8 × 5.5 × 4 cm, was well-circumscribed, unilocular, and filled with a mucoid yellowish fluid. Histologically, the cystic mass was lined by gastric epithelium with pyloric glands (Fig. ), transitioning focally into squamous epithelium (Fig. ) and in some areas into pseudostratified columnar ciliated epithelium (Fig. ). A small part of the mucosa-like wall had ulceration accompanied by inflammation (Fig. ). There was no evidence of cartilaginous tissue in the wall. There were also bundles of smooth muscle in the wall. This finding suggested a GDC . The histological examination of splenectomy showed pronounced cord congestion with reactive follicular hyperplasia and increased deposition of hemosiderin. After 10 months, there were no signs of local complication, and the patient was successfully weaned from steroids and had complete resolution of hemolytic anemia with negative direct antiglobulin tests.
pmc-6306005-1	The patient was a 22-year-old man who came from a non-consanguineous family. Before he was referred to our department, he had a history of antecedent influenza 10 days ago. He started to have progressive limb weakness and numbness 5 days ago. He also complained of persistent soreness in both inferior calves and numbness in the distal limbs. The symptoms gradually worsen, and caused virtually bed bound. Neurological examinations revealed a length-dependent decrease of touching, temperature, pain, and vibration sensations below the knee and the wrist joints. Muscle strength was grade 2−/5 (Medical Research Council scales) in the proximal lower limbs, grade 4/5 in the distal lower limbs, grade 4−/5 in the upper limbs, and grade 3/5 in the neck flexion. The cranial nerves were intact. Deep tendon reflexes were not elicited. Serum creatine kinase (CK) was 5809 IU/L (normal 1–171 IU/L). Blood count, blood biochemistry, inflammatory tests, thyroid hormones, serum vitamin B12 and folic acid were in normal limits. The panel of anti-ganglioside antibodies including GQ1b, GT1b, GD1b, GD1a, GM2, and GM1 was negative. Cerebrospinal fluid (CSF) results were normal at 6 days after the onset of disease. Blood acylcarnitine profile before treatment revealed a combined elevation of short-, medium-, and long-chain acylcarnitines. Urine organic acid analysis indicated an increase of multiple metabolic acids. Motor nerve conduction velocity (MNCV) showed that a borderline decrease of compound muscle action potentials (CMAP) was recorded in the bilateral median, bilateral ulnar, and left peroneal nerves (Table ). Sensory NCV showed normal potentials can be recorded in both sural nerves and median nerves. The latency of H reflexes and F waves were normal in all nerves tested. Needle electromyogram showed mildly decreased motor unit action potentials (MUAP) in the right gastrocnemius muscle and anterior tibialis muscle.
pmc-6306005-2	The patient was a 55-year-old man who came from a non-consanguineous family. He suddenly began to have muscle weakness in both lower limbs; meanwhile he felt numbness of the distal lower limbs. The weakness quickly ascended to upper limbs 2 days later and then progressed into difficulty of swallowing 3 days later. He also complained of tightness around the waist and abdomen, but the bladder function was normal. Muscle strength was grade 4/5 in the foot dorsiflexors, grade 5/5 in the plantar flexion, grade 2/5 in the proximal lower limbs, grade 4/5 in the hand gripping, and grade 3/5 in the proximal upper limbs. The sensations of pain, vibration, and joint position perception reduced below the knee. Deep tendon reflexes were not elicited in the lower and upper limbs. Serum CK was 334 IU/L. Blood count, blood biochemistry, inflammatory indexes, thyroid hormones, serum vitamin B12 and folic acid were in normal limits. The panel of anti-ganglioside antibodies including GQ1b, GT1b, GD1b, GD1a, GM2, and GM1 was negative. Laboratory panels of CSF were normal at 5 days after the onset of disease. Spinal MRI was normal. Blood acylcarnitine profile before treatment revealed a multiple increase of short-, medium-, and long-chain acylcarnitines. Urine organic acid analysis showed a significant elevation of 2-hydroxyglutaric acid and 2-hydroxyadipic acid. MNCV of the case 2 revealed decreased amplitudes of CMAP in both peroneal nerves, but other nerves were intact (Table ). Sensory NCV showed significant impairments in nerves tested. The latency of H reflexes and F waves were normal in all nerves tested. Needle electromyogram of gastrocnemius muscle showed a little short duration and low amplitude MUAP. Muscle biopsies were conducted at the right biceps brachii in the two patients. The muscle specimens exhibited similar pathological changes. Most myofibers were filled with numerous small vacuoles, but without significant variations of fiber diameter or proliferation of connective tissue (Fig. a and b). The lipid droplets were accumulated in the fibers with vacuoles (Fig. c and d), especially affecting the type I fibers. Nicotinamide adenine dinucleotidetetrazolium reductase (NADH-TR) stain revealed many dark particles in the fibers with numerous lipid droplets. A few fibers with negative cytochrome c oxidase (COX) were observed in the two cases. Neurogenic patterns such as grouping of angular atrophic fibers or target-like fibers were not observed in the acid or alkaline ATPases stain. Genetic test was performed in the patients through targeted next generation sequencing (NGS) after informed consents were written. The NGS was conducted on selected subjects using Agilent SureDesign Panel kits for inherited myopathy and inherited peripheral neuropathy. Genetic sequencing disclosed compound heterozygous mutations: c.265-266delCA and c.1211 T > C (p.M404 T) in the case 1 (Fig. a); c.34G > C (p.A12P) and c.736G > A (p.E246K) in the case 2 (Fig. b). The variants co-segregated with their parents: c.265-266delCA was from the mother and c.1211 T > C was from the father; c.34G > C was from the father and c.736G > A was from the mother. The variants c.736G > A and c.265-266delCA were not found in the 1000 genomes database, ExAC database, and gnomAD database, but the variants c.34G > C and c.1211 T > C had a very low allele frequency (Table ). A homology search in different species demonstrated that the amino acid at residues 12, 246, and 404 were highly evolutionarily conserved, respectively. The variants were predicted to be damaging by several in silico tools (Table ). The pathogenicity of variants was evaluated according to the American college medical genetics and genomics (ACMG) criteria (Table ). No other causative mutations associated with metabolic myopathies or inherited neuropathies were found in the target gene kits including the ETFA, ETFB, flavin adenine dinucleotide synthetase 1 (FLAD1), and solute carrier family 25 member 32 (SLC25A32) genes. The two patients were initially treated with riboflavin (150 mg/d), L-camitine (2 g/d), and coenzyme Q10 (150 mg/d). One week later, limb weakness improved dramatically, and muscle strength nearly recovered 4 weeks later. The level of CK also returned to normal limits. The sensory disturbances showed no improvement; even the tightness around waist and abdomen in case 2 became worse than ever 4 weeks later. However, the patients reported significant improvement of paraesthesias after long-term administration of riboflavin (30 mg/d), CoQ10 (100 mg/d), and cobalamine (500μg/d) for 12 months.
pmc-6306278-1	Our patient was born at 33 weeks of gestation by cesarean section to a 36-year-old gravida 3, para 2 woman after a prenatal diagnosis of left CDH (31 weeks' gestation). Postnatal chest X-rays confirmed the left CDH, with the liver in the thorax. Initial echocardiogram revealed only a small patent ductus arteriosus. There were no signs of PH at this time. At 24 hours of life, she underwent surgical repair of a huge diaphragmatic defect (type D according to the CDH Study Group staging system) that required a silastic patch closure. Weaning from mechanical ventilation was achieved on postoperative day (POD) 4, but 3 days later she was reintubated for recurrent respiratory distress. Respiratory support was finally stopped on POD 26, and she was discharged home on POD 58. Predischarge echocardiography was unremarkable. The infancy was uneventful and the quality of life was excellent. She underwent periodic follow-up visits that revealed gastroesophageal reflux (GER) and initial mild scoliosis. At the age of 10, she was admitted for abdominal pain, vomiting, and dyspnea, and GER disease and severe PH were diagnosed. Heart ultrasound showed an estimated systolic right ventricular pressure of 130 mm Hg, with a systolic blood pressure of 100/50 mm Hg. Medical treatment for PH was initiated, including sildenafil, bosentan, and furosemide. Since PH progressively worsened despite maximal medical treatment, leading to end-stage respiratory failure, at the age of 14, she was listed for H-Ltx, and 3 months later she received the new organs. Postoperative course was characterized by short-term complications such as severe central venous line-related infections, massive pleural effusion and ascites, and delayed complications, including CDH recurrence with intestinal obstruction, requiring laparotomy and ileostomy formation. In addition, she suffered from recurrent respiratory infections, severe malnutrition, and drug-induced diabetes, significantly impacting her quality of life. With aging, scoliosis and GER also aggravated, requiring posterior vertebral arthrodesis and Nissen's fundoplication at 16 years of age. At 17 years of age, she developed a further episode of pneumonia-related respiratory failure and required a tracheostomy for multiple failed attempts of extubation. Bronchiolitis obliterans deteriorated her respiratory function, and the same year she was relisted for Ltx and underwent her second bipulmonary transplantation. Despite the second transplant, her general conditions rapidly deteriorated, she developed chronic lung rejection, and she eventually died at the age of 18, 4 and 1.5 years after the first and the second Ltx, respectively.

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