The patient in our case was a 51-year-old man who had been treated 20 years ago with ascending-to-descending EABG using a 22-mm Dacron graft for CoA. Moreover, he had anatomical anomalies of the right aortic arch with Kommerell’s diverticulum. Eight years ago, the patient experienced hemoptysis due to a PA on the distal anastomosis site and was treated by TEVAR using the GORE TAG Stent Graft System (34 mm × 20 cm) (W.L. Gore & Associated, Inc., Flagstaff, AZ, USA). After TEVAR, the size of the PA decreased, and the patient did not experience hemoptysis.
However, due to a recurrence of hemoptysis, the patient was admitted to a hospital. On admission, contrast-enhanced computed tomography (CT) revealed the presence of a PA in the distal anastomotic site of the graft, which appeared to be the cause of hemoptysis (Fig. ). The stent graft was observed in the distal anastomotic site, as was massive blood flow from the descending aorta. Therefore, the patient was transferred to our institution. Blood pressure was normal on examination, and we initially planned to treat the patient using TEVAR. The stent graft is ideally deployed from a site distal to the coarctation to cover the PA, but in this case, it could not be placed proximally to the PA owing to the anatomical form. Thus, we decided to replace the descending aorta and subsequently performed end-to-side anastomosis of the replaced descending aorta with the graft that was surgically constructed 20 years ago.
The patient underwent a right third intercostal thoracotomy. Because large portions of the lung had adhered to the ascending-to-descending EABG and PA, we modified the initial surgical plan to perform replacement of the descending aorta, followed by end-to-side anastomosis of the graft to the newly replaced descending aorta. The native descending aorta proximal to the anastomosis site was accessible; therefore, we decided to completely transect the descending aorta for decompression of the PA (Fig. ). The descending aorta was clamped between the coarctation and PA and transected. Both sides were closed using 4-0 polypropylene with pledget (ETHICON®). Postoperative contrast-enhanced CT showed the complete disappearance of the diseased aortic arch, including the ruptured PA (Fig. ). The postoperative course was uneventful, and the patient was transferred back to the previous hospital on the 13th postoperative day to continue rehabilitation. The patient is doing very well at 5 months after the surgery.


Case 1 was a 36-year-old female with presenting BCVA counting fingers OS due to vitreous hemorrhage (VH). Oral transamin and topical steroid treatment were given. FA showed vascular tortuosity, peripheral retinal NV, and ME (). OCT also revealed ME (). Intravitreal aflibercept was used as rescue therapy due to persistent retinal NV and ME after administration of focal retinal photocoagulation, periocular depot triamcinolone acetonide, and intravitreal ranibizumab injections. After the first intravitreal aflibercept injection, the retinal NV regressed () and ME decreased (). ME recurred after 5 months (). Supplemental retinal photocoagulation was performed, and the second intravitreal aflibercept injection was given. The retinal NV regressed again and ME resolved. Recurrent VH was noted after 15 months, and a third intravitreal aflibercept injection was given. VH and ME were then resolved (). The patient's BCVA improved to 20/25 and was followed up for 43 months. Her intraocular pressure was within normal limits during the whole course.


Case 2 was a 27-year-old female with presenting BCVA 20/30 OD due to VH. Oral transamin and topical steroid treatment were given. FA showed vascular tortuosity, peripheral retinal NV, and cystoid macular edema (CME) (). Intravitreal aflibercept was used as rescue therapy due to persistent CME and retinal NV after administration of periocular depot triamcinolone acetonide injection and topical nepafenac (). After the first intravitreal aflibercept injection, the retinal NV regressed () and CME subsided (). The patient's BCVA improved to 20/25. However, ME recurred after 3 months (). Thereafter, intravitreal aflibercept injections were administered once every three months to keep her BCVA 20/20 (). The patient has been followed up for 28 months. Her intraocular pressure was within normal limits during the whole course. The treatment was well tolerated by both patients without significant adverse events.


A 77-year-old woman presented with a 1-day history of constant, sharp, right upper quadrant and epigastric abdominal pain, associated with multiple episodes of non-bloody emesis. She did not identify any triggers for the pain, and specifically stated that the pain is not worse post-prandially. She endorsed a history of recurrent episodes of similar pain over the past several months that were 10–15 min s in duration and always self-resolving. Her past medical, surgical, and family history were non-contributory. She was on no home medications. Laboratory findings were initially unremarkable, but upon re-draw the next day, white blood cell count and C-reactive protein (CRP) were mildly elevated. An ultrasound of the abdomen showed a distended gallbladder with mild pericholecystic fluid, a positive sonographic Murphy’s sign, but no cholelithiasis or extrahepatic bile duct dilatation (). Given these findings, a diagnosis of cholecystitis was questioned, and a lack of cholelithiasis prompted a CT scan of the abdomen and pelvis for further confirmation. The CT also showed a distended gallbladder with mild pericholecystic fluid without additional findings of cholelithiasis, malignancy, or other biliary pathology (). The gallbladder was not enhancing in the CT scan, and the cystic artery was not identified either (a.). At this point, the patient was admitted under the general surgery service with a presumed diagnosis of acalculous cholecystitis. However, she had no other medical comorbidities that are usually found in patients with acalculous cholecystitis. Due to diagnostic uncertainty, a hepatobiliary iminodiacetic acid (HIDA) scan was obtained that showed normal hepatic uptake and excretion, normal excretion in bile ducts, but an ejection fraction of the gallbladder could not be assessed because of incomplete filling. In fact, there was no contrast uptake in the gallbladder, suggesting a complete occlusion of the cystic duct from an unknown cause (). Following the HIDA, an MRCP was obtained to rule out other potential causes of gallbladder inflammation. Similar to the US and CT, the MRCP demonstrated gallbladder distension, gallbladder wall thickening at 3 mm, mild pericholecystic fluid, without cholelithiasis (). Imaging findings in all studies were interpreted as acalculous cholecystitis. The patient was initially treated with 5 days of intravenous ceftriaxone and metronidazole. Despite adherence to the antibiotic regimen there was no improvement in symptoms. Eventually, due to the lack of resolution with antibiotics, a decision was made to proceed with cholecystectomy. A percutaneous decompression tube was not pursued because the patient was otherwise healthy and a good operative candidate.
The procedure was initiated laparoscopically, but there were dense adhesions in the right upper quadrant not allowing for safe visualization of the gallbladder, which resulted in conversion to an open cholecystectomy. Intraoperatively, the gallbladder was found to be 180 degrees torted in an anticlockwise direction. The torsion caused a complete occlusion of the cystic duct and cystic artery resulting in a gangrenous and necrotic gallbladder (). In retrospect, the occlusion of the cystic duct on HIDA was probably the result of a complete torsion of the cystic duct. The gangrenous gallbladder was then removed in a retrograde fashion. The final pathology reported gangrenous cholecystitis with hemorrhage and necrosis at the cystic duct margin. The patient had complete resolution of pain and nausea on post-operative day 1 and was appropriately discharged by post-operative day 2. At her 6 month virtual follow-up, she was content with the overall outcome and was completely symptom free.


A 54-year-old Caucasian male presented to the emergency department with severe chest pain, dyspnea, and dizziness along with left arm pain and weakness. The symptoms occurred while he attempted to install an overhead light fixture. His perceived dizziness was further described as lightheadedness and presyncopal symptoms, which always occurred when he was working with his left arm, particularly if his left arm was raised above his head. He stated that his left arm pain and weakness had been progressive to the point that he could no longer work as he could not hold his tools. Previously, he had been seen in the outpatient cardiology clinic multiple times throughout the last two years with complaints of recurrent angina. However, despite medical recommendations, he never underwent a coronary angiogram or stress test for further evaluation due to severe fear and anxiety associated with these procedures.
Past medical history was significant for hypertension, diabetes, hyperlipidemia, smoking, anxiety, and ischemic cardiomyopathy. A component of previous treatment for the ischemic cardiomyopathy was a four-vessel CABG in 2008, achieved by grafting the LIMA to the left anterior descending artery and SVGs to a diagonal branch, obtuse marginal branch, and posterior descending artery. Vitals were significant for a 23 mmHg difference in systolic blood pressures obtained from bilateral upper extremities, and physical examination revealed diminished pulses in the left arm, raising the suspicion for subclavian stenosis. Coronary and bypass angiography was performed due to concerns of unstable angina and revealed 100% occlusion of the proximal left subclavian artery (Figure ).
Angiogram confirmed complete flow reversal from the proximal left subclavian artery to the LIMA (Video ).
The LIMA had dilated from approximately its average size of 2 mm to 10 mm, which is approximately the average size of the subclavian artery. Bilateral carotid duplex revealed no hemodynamically significant stenosis. Left carotid-subclavian bypass surgery was performed which relieved his exertional angina along with dizziness and left arm discomfort.


A 5-month 24-day-old baby girl came to our hospital because of “9 days of abnormal liver function.” She was first admitted to another hospital for “bronchial pneumonia.” During her hospitalization, she was found to have increased transaminases (alanine aminotransferase [ALT] 122–157 U/L, aspartate aminotransferase [AST] 75–120 U/L) and was treated with ceftazidime injection, compound glycyrrhizin injection, and fluid replacement. Her liver function did not improve. She occasionally coughed, easily cried, and had a poor appetite. She produced stools 3 to 5 times a day that were mushy and oily. She was the third child of healthy and unrelated parents and was born on the 37th week of gestation with a birth weight of 2900 g. She had 2 healthy elder sisters. At the time of admission, the patient was 60 cm tall and weighed 5000 g; thus, she was below the third percentile. Her lung examination was basically normal. She had no hepatomegaly, splenomegaly, or enlarged lymph nodes. This study was approved by the ethics committee of the Xiamen Children's Hospital, and written consent for its publication was provided by the patient's parents.
Her white blood cell count was 8.68 × 109 cells/L, absolute neutrophil count was 3.12 × 109 cells/L, number of platelets was 560 × 109 cells/L, and hemoglobin concentration was 114 g/L. Her 25-hydroxyvitamin D levels were low (29.7 ng/mL). AST (114 U/L) and ALT (163 U/L) levels were elevated, and total cholesterol was 2.16 mmol/L. Prothrombin time; albumin levels; creatine kinase; serum IgA, IgG, IgM; and other serum biochemical parameters were within normal ranges. The patient was positive for fecal fat globules.
Digestive system ultrasound found no obvious abnormalities in the gallbladder, pancreas, or spleen, and no obvious abnormal echoes were seen in the adrenal glands.
The patient's blood sample was analyzed, and the results showed 2 heterozygous mutations in the SBDS gene (Table ). First, c.184A>T heterozygous mutations, resulting in amino acid changes producing p.K62X mean nonsense mutations. The transformation of A to G of 185 non-pathological silencing nucleotides in SBDS gene was also detected in the heterozygosity (Fig. ). On family analysis and verification, there were no mutations at this locus in the patient's father, and heterozygous variation was found at the locus in the mother. The frequency of this mutation in the normal population database was 0.00190. Second, c.258+2T>C synergistic mutations are splicing mutations, resulting in the splicing of amino acids. After family analysis and verification, the parent of the examinee had heterozygous variation and the mother had no variation at the locus. The frequency in the normal population database was 0.00930 (Fig. ).
After admission, the patient was provided compound glycyrrhizin, Newtide formula milk supplemented with probiotics, fat-soluble vitamins, oral medication to adjust the spleen and stomach, and other symptomatic treatments. The stool traits improved, and the levels of liver function transaminases decreased compared with before.
We performed a search for SBDS-related literature in PubMed published from January 2014 to December 2018, and, after screening and exclusion of duplicate articles, 12 of them met the standards, and 119 cases were included.[ Clinical manifestations (Table ) and genetic test results (Table ) were analyzed.


More than 1 year ago, a 46-year-old Chinese man presented to our department with blurred vision in his left eye. At the time, he was diagnosed with acute central serous chorioretinopathy. Oral medications were prescribed; however, he was lost to follow-up. He had excellent uncorrected distance acuity (20/20 in both eyes). Records of optical coherence tomography (OCT) B-scan showed neurosensory detachment at the central macula.
He revisited our department recently and complained of blurred vision again since 1 month. At this visit, he underwent a complete ophthalmic examination, including slitlamp biomicroscopy, best-corrected visual acuity (BCVA), non-contact tonometry, detailed fundus examination, fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA), OCT, and OCTA.
The BCVA was 20/20 OD and 20/25 OS. Intraocular pressure was within normal limits, and anterior segment examination was unremarkable in both eyes. Fundus examination of the right eye was normal, but the left eye showed a shallow sensory detachment in the macula (Fig. A). On FFA, the lesion revealed patchy hyperfluorescent dots temporal to the fovea in the early and late phases (Fig. B). ICGA also revealed patchy hyperfluorescent dots in the middle and late phases (Fig. C). OCT B-scan showed a dome-shaped serous detachment of the neurosensory retina and a flat serous PED at the first visit (Fig. D) and subsequent visit (Fig. E). OCTA, reported to be useful for identifying hidden CNVs that could not be found via FA and ICGA, did not show a distinct CNV (Fig. F).
The patient was diagnosed with chronic CSC. Treatment employed was half-dose PDT with verteporfin. Fifteen minutes after the start of the intravenous infusion of verteporfin (3 mg/m2), a 689 nm laser was delivered (600 mW/cm2; 83 s). The delivered radiation covered the hyperfluorescent area of the corresponding serous subfoveal PED in the middle or late phase of the ICGA. Three weeks later, the patient complained of sudden blurred vision and revisited our department. Fundus examination showed macular hemorrhages (Fig. A) with a BCVA of 20/250. OCTA showed a distinct area of flower-like CNV located within the deep retinal slab (Fig. B). OCT B-scan revealed subretinal hyperreflective material corresponding to the CNV complex located above the retinal pigment epithelium (RPE) (Fig. C). Unfortunately, secondary CNV had developed after half-dose PDT in this case.
Next day, intravitreal injection of aflibercept (2 mg) was administered. One month later, the patient's symptoms were relieved and his BCVA improved to 20/100. Fundus examination revealed almost complete resolution of macular hemorrhages. OCTA showed the CNV had completely disappeared. To consolidate treatment, a second intravitreal injection of aflibercept (2 mg) was administered. Two months later, the BCVA improved to 20/25. Macular hemorrhages were completely resolved in the fundus (Fig. D) The CNV did not recur in the OCTA image (Fig. E), but a small PED was present on the OCT B-scan (Fig. F).


A thirteen-year-old boy presented to the emergency department with pain and bleeding from the perineal region along with the penetrating construction iron rod in situ in the perineal region for 15 h after sustaining a fall injury from the rooftop. He was stuck at the top of the iron bar after injury and his relatives cut the bar from its base supporting him from the adjoining house to prevent any possible movements and rushed him to the nearby hospital, and was referred to our center for further management.
On arrival to our Emergency Department, the patient was conscious, tachycardic (HR-140bpm), tachypneic, blood pressure of 120/80 mmHg, and other vitals stable. The patient did not any have relevant past history. However, he was bleeding from the perianal region, and a broken metal rod of about 2 cm diameter in situ with entry and exit wound in perineal and left loin region respectively was present (). Emergency management was done according to advanced trauma life support (ATLS) guidelines. Urinary catheterization and rectal examination couldn’t be performed due to the injury and presence of the rod. On local examination, the rod of 2cm × 2cm thickness entered the perineal region 2 cm above the anal opening along with an exit wound of 2cm × 2cm in the left loin region (). Tetanus vaccination and broad-spectrum antibiotics with aerobic and anaerobic coverage were administered.
Considering hemodynamic stability, radiographic investigations were performed. X-ray of the cervical and dorsal spine revealed no spinal injury and chest X-ray was normal. Computed Tomography (CT) scan of the abdomen and pelvis revealed a metallic foreign body (iron rod) of the approximate diameter of 18 mm penetrating through the perineal region and coursing posterosuperior to the left, posteriorly to the urinary bladder, anterior to left ala of sacrum, left anterolateral aspect of the rectum, close to the left transverse process of L4-L5 vertebrae, along the left paraspinal region and then exiting outside of the left posterior upper abdominal wall at T10 vertebrae level with no obvious injury of the urinary bladder, rectum and other visceral organs and major large arteries (, ).
Considering the possibility of rectosigmoid/retroperitoneal injury, an exploratory laparotomy was done with lower midline access and after meticulous observation, no injuries to vital organs by the rod were found. Perioperatively, 2 cm × 2 cm thickness iron rod was passing through the perineal body with penetration of urogenital diagram passing through the iliopsoas muscle till the lower border of the kidney with exit wound of 2 cm × 2 cm in the left lumbar region (). No pathological findings other than about 100 ml of clotted blood in the peritoneal cavity along with a small perforation in the transverse colon was detected. Surprisingly, there was no injury to the rectum, urinary bladder, small bowel, kidney, spleen, major vessels, urethra, external genitalia, and external anal sphincter. The rod was removed slowly and steadily under direct vision ensuring no more damage (). The perforation of the transverse colon and the defect in the urogenital diaphragm were repaired. The perineal wound was cleaned and allowed to heal secondarily and a long Penrose drain was placed into the entry hole. The lumbar exit hole was closed. The procedure was performed by experienced pediatric surgeons’ team of Tribhuvan University, Teaching Hospital encountering no any other complications and was well tolerable by the patient.
The patient recovered well and was discharged on the 9th postoperative day, having remained in the pediatric intensive care unit for four days, without any complications related to walking, urination, and defecation. On follow up after 3 weeks, wounds were healthy and the perineal wound had healed.


Patient 1: a 37-year-old male (46, XY karyotype), issued from a consanguineous marriage, was diagnosed with 11β-OHD at the age of three. The disease was revealed by peripheral precocious puberty with an increased penile size, pubic hair development and bone age advancement. Laboratory findings at diagnosis was characterized by high serum concentrations of 11-deoxycortisol and adrenocorticotropic hormone (ACTH) with low plasma renin activity (). Genetic analysis found a homozygous p.Gly379Val (c.1136G>T) mutation in exon 7 of the CYP11B1 gene. During his follow-up, grade 3 hypertension was discovered at the age of 25 associated with hypokalemia treated by Calcium channel blocker (amlodipine 10 mg q.d.) and Beta-blocker (atenolol 50 mg q.d.). It has been complicated only by hypertensive retinopathy grade 1. The patient was treated by hydrocortisone 25mg b.i.d. Acute adrenal deficiency didn´t occur during the follow-up despite bad compliance of the treatment. He presented some episodes of abdominal pain that was alleviated after the correction of hypokalemia. Spironolactone 50 mg q.d. was prescribed later, at the age of 36, due to persistent hypokalemia. Progressive weight gain was observed since the age of 25 passing from 64 Kg to 90 Kg at the age of 36. He had a metabolic syndrome with an android fat distribution (waist circumference = 102 cm) and low HDL level (). External genitalia examination and bone density were normal. The patient was married and he had two healthy children aging respectively of three and one-year-old.


Patient 2: a 35-year-old female (46, XX) was diagnosed with 11β-OHD at the neonatal age. The disease was revealed by the virilization of the external genitalia which was corrected surgically. The patient had a normal blood pressure during her regular check-up despite the presence of hypokalemia (). She was treated initially by hydrocortisone 30 mg b.i.d. and she didn´t have during her follow-up an acute adrenal deficiency. She had metabolic syndrome, class I obesity and polycystic ovary syndrome (PCOS) since the age of 28. The diagnosis of PCOS was considered regarding the presence of spaniomenorrhea, clinical (hirsutism, alopecia) and biological (testosterone level = 6.2 ng/ml) hyperandrogenism. The patient´s weight increased from 75 Kg at the age of 28 to 94 Kg at the age of 32, date of which the dose of hydrocortisone was decreased to 20 mg b.i.d. She had since lost 8 Kg and had normal menstrual cycles. Her bone density was normal two years ago. Spironolactone was also introduced due to persistent hypokalemia.


Patient 3: a 33-year-old female (46, XX) was diagnosed with 11β-OHD prenatally. Her mother was treated during pregnancy with dexamethasone. However, since she had also virilization of the external genitalia, she was operated on at the neonatal age. Genetic analysis found the same mutation as her brother, patient 1. The patient had an irregular follow-up and she was treated initially by hydrocortisone 30 mg b.i.d. She didn´t have a history of acute adrenal deficiency. Her menarche was at the age of 12. She had PCOS with hirsutism and irregular cycles, treated by estrogen therapy (estradiol 2 mg q.d.) associated with cyproterone acetate 50 mg q.d. At the age of 32, the patient was admitted for sore throat and repeated vomiting. Her body temperature was 38°C. She had a normal body mass index and a blood pressure of 120/90 mm Hg. She received amoxicillin 3 g t.i.d. for tonsillitis. Biochemical analysis revealed hypokalemia (2.7 mmol/L) without electrocardiographic changes. She was treated initially by intravenous potassium chloride then by an oral solution. Hypokalemia persisted after the withdrawal of potassium substitution and 24-hour ambulatory blood pressure monitoring revealed a mean systolic blood pressure of 169 mm Hg and a mean diastolic blood pressure of 116 mm Hg. The patient was discharged later with spironolactone 50 mg q.d.


Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
A 24-year-old man riding a motorcycle collided with a car while turning to the right. He fell off the motorcycle after the collision, and was injured by another car. He had no previous medical history. When he was brought to our emergency department in an ambulance, his airway was patent, he was tachypneic, hypotensive, tachycardic, and his Glasgow coma scale score was 7 (E1V2M4). Intubation, bilateral chest drainage, and blood transfusion were performed. Following assessment by whole-body computed tomography (CT), he was diagnosed with bilateral pneumothorax, liver and spleen injuries, fractures of the left acetabulum, right patella and tibial plateau, with open fractures of the shaft of the right femur and distal third of the left femur (Fig. ). External fixation and irrigation of both thighs were performed in the operating room. The liver and spleen injuries were treated conservatively. After surgery, his consciousness disorder persisted. Initially, hypoxia was not accompanied by significant changes in chest radiographs; however, serial chest radiographs showed progressive bilateral pulmonary opacities consistent with ARDS (Fig. A and B). Contrast-enhanced CT also showed bilateral patchy gland glass opacity and consolidation matching chest radiographs, and there was no filling defect in pulmonary artery. Arterial blood gases on the 4th day of admission showed a PaO2/FiO2 (P/F) ratio of 100 mmHg under 10 cm H2O of positive end-expiratory pressure (PEEP). In addition, the patient developed subconjunctival, abdominal, and precordial petechiae (Fig. ). He remained tachycardic, febrile with a body temperature >38°C, and was jaundiced. Laboratory data showed exacerbation of anemia (hemoglobin, 9.1 × 10 g/L), decreased platelet count (88 × 109 /L), and elevated total bilirubin levels (8.9 × 10 μmol/ L). Gurd and Wilson criteria (3 major and 5 minor criteria) and Schonfeld scoring system were used for the diagnosis of FES. The criteria of both scoring systems were met, thereby supporting the positive diagnosis of FES (Table ).[
The patient had type 1 respiratory failure which gradually worsened with conventional lung-protective ventilation. Due to a persistent consciousness disorder, prophylactic antiepileptic drug administration, anticerebral edema therapy, and targeted temperature management using an intravascular temperature control catheter were performed.[ On the 6th day of admission, the Murray score was 3.5 indicating severe lung injury: P/F ratio of 81 mmHg (4 points), pulmonary edema in all lung fields on chest X-ray (4 points), PEEP of 14 cm H2O (3 points), compliance of 23.3 ml/cm H2O (3 points). Because his cardiac function was not reduced and hemodynamic status was maintained, we chose VV-ECMO over venoarterial-ECMO.[ A 23 French multi-stage drainage cannula was inserted from the left femoral vein to the inferior vena cava, and a 17 French single-stage return cannula was cannulated from the right internal jugular vein to the superior vena cava. The ECMO rotation speed was 3300 r/minute and the flow rate was 4.5 L/minute with 100%FiO2 and 4.5 L/minute sweep gas flow. Under the condition, his peripheral oxygen saturation was maintained >95% and blood gas analysis showed a pH of 7.42, PO2 of 95 mmHg, and PCO2 of 46.6 mmHg. Although lung protection management was continued with high PEEP and low tidal volume after VV-ECMO introduction, improvement in respiratory condition was not observed. Therefore, we decided to convert the external fixation to internal fixation to begin prone position therapy. Osteosynthesis was performed on the 9th day of admission under VV-ECMO. In the supine position a tourniquet was applied on the left side. The lateral parapatellar approach was used to reduce the fracture and fix the screws and lateral locking plate (Fig. A). The tourniquet was released to place the screws in the proximal holes of the plate, following which there was continued congestive bleeding. Heparin had been introduced into the circuit at the beginning of the operation, but due to a large amount of blood loss, protamine sulfate, an antagonist for heparin, was administered midoperation. The bleeding was controlled by closing the left knee wound and inserting a drain. Osteosynthesis of the right femur was then performed using a retrograde intramedullary nail (Fig. B) without any serious complications. The total operation time was 4 hours and 29 minutes and the total blood loss amounted to 3800 g. Sixteen units of red blood cell transfusion, 20 units of platelet transfusion, and 16 units of fresh frozen plasma were needed. The ECMO circuit was run heparin free for 2 days postsurgery.
Prone-position ventilation was initiated on the second day postsurgery after the hemodynamics became stable. The patient was placed in the prone position for 16 hours a day. Low tidal volume ventilation (6 ml/kg) and an infusion of neuromuscular blockade was introduced. To address severe acute kidney injury due to hemolysis, we also started continuous renal replacement therapy on the 14th day. For 4 days, the patient was managed in the prone position. His respiratory condition and chest radiographs improved steadily over the 8 days following osteosynthesis, and VV-ECMO was discontinued on the 17th day (Fig. C). The ventilator was removed on the 28th day. At that time, his respiratory status improved to P/F ratio: 370, and multiple petechiae disappeared. His conscious level normalized without residual central nervous system complications.


A 29-year-old woman with a 1-day history of backache was admitted to our hospital. Physical examination revealed mild weakness and hypermyotonia in the right leg. Lumbar CT revealed bony destruction in the L3 vertebral body and its right adnexa, with a slightly high-density extraspinal soft tissue mass formation. A slight increase in CA724 to 11.29 U/ml was observed, while the other tumor indicators were in the normal range.
Subsequently, whole-body PET/CT examination was performed. The imaging showed a 43×31 mm paravertebral heterogeneous soft tissue mass along the spinal nerve at the L2-L3 level (Fig. a), with strong FDG uptake, accompanied by bone destruction of the L3 vertebral body and its right adnexa (Fig. b). The maximum standardized uptake value (SUVmax) was about 8.10 and 9.24 on early and delayed imaging, respectively, and the retention index of FDG was about 14.1%. An 18 × 10 mm nodule with increased FDG uptake was found in the lateral lobe of the left liver (Fig. a and 2b), with a smooth edge and a prominent anterior margin, which appeared to be consistent with a metastatic nodule. The CT value was approximately 44 HU. The SUVmax of this nodule on early and delayed imaging was approximately 2.98 and 3.79, respectively. The FDG retention index was approximately 27.2%.
A few days later, puncture biopsy of the L3 bony destruction and surrounding soft tissue mass was performed. The smears showed small syncytial tissue fragments and sheets composed of pleomorphic elongated spindle-shaped and ovoid cells containing abundant cytoplasmic pigment associated with numerous pigment-laden macrophages (Fig. a). Immunophenotyping revealed positive staining for S-100 (Fig. b), vimentin, SOX10, HMB45, MiTF, and Melan-A, but negative staining for EMA and CD57. Thus, the final diagnosis was spinal MS with hepatic metastasis.
The patient underwent 6 cycles of endostar and temozolomide combined chemotherapy, the specific regimen was as followed: Endostar 15 mg intravenous drip, continuous administration from day 1 to 14, and temozolomide 300 mg was administered continuously from day 1 to day 5, with a cycle every 28 days. A whole-body PET/CT examination was performed at another hospital 6 months after the end of chemotherapy, and no active tumor lesions with increased FDG uptake were found in the lumbar spine and liver, suggesting that the patient met the criteria for complete remission. The patient has survived for 1 year since the initial diagnosis.
Ethical approval was not required because this was a case report of the clinical information of the patient. Written informed consent was obtained from the patient for the publication of this case report and accompanying images.


The patient is a 58-year-old male residing in the city of Philadelphia, Pennsylvania, USA. He lives by himself in an apartment. He is currently disabled but was working at an appliance repair store up until a few years ago. He carries a history of hypertension, type 2 diabetes mellitus, hypertriglyceridemia and lumbar spondylosis. He is an active smoker and smokes approximately a pack of cigarettes daily. He reported compliance to all his medications (25 mg hydrochlorothiazide and 80 mg valsartan that he takes every day for hypertension; 500 mg twice daily of metformin and 50 mg daily sitagliptin for type 2 diabetes mellitus; 20 mg daily pravastatin and over the counter fish oil for the hypertriglyceridemia). Other than smoking, he denied any concern in terms of the complications from these comorbidities. Urine toxicology screen was negative for any illicit substances. He denied peripheral vascular disease (PVD), cardiovascular or neurological conditions though he did not recall getting tested for PVD or diabetic neuropathy as such.
He was also diagnosed with OCD at the age of 26 years but reported compulsive behavior from his adolescence. As an adolescent, he first developed compulsive squeezing of his acne and picking of his facial hair. A few years later, he had to compulsively pick the hair, the acne and skin in his entire body, more so in his legs. At times, he reported severe anxiety associated with these skin-picking episodes and even reported a couple of visits to the emergency room with the symptoms of OCD. He was taking quetiapine 50 mg daily for his OCD.
Over the last few months or so, he reported he became more and more compulsive in picking the skin on his toes and his feet. Though he was not able to specify the exact times he was picking his skin every day, he did report that the picking would get worse whenever he gets nervous and anxious. He described his picking as constant on a daily basis, sometimes that episode could last for minutes. This compulsive behavior started off with picking the skin around his nail beds and slowly got worse. He reported few occasions of having painful sores and wounds due to the skin picking when he applied topical over the counter antibiotic and antiseptic creams. However, he could not resist picking the scars over these wounds and the wounds would never heal. Over time, he reported that “he gave up” on his skin picking behavior as he noticed that the left leg wound was gradually getting worse. Due to the worsening pain and foul-smelling discharge from the wound, he decided to come to the emergency room (ER).
When he presented to the ER, he was found to have an extensive wound on distal left foot with exposure of the underlying muscle tissue, oozing of blood and surrounding erythema (Figure ).
He had a low-grade temperature of 100.2 F, heart rate of 103 beats/min and blood pressure 133/82 mm Hg. Systemic examination was normal other than sinus tachycardia and the above-described wound. The patient’s initial baseline laboratory data at the time of admission showed a leukocytosis with a white cell count up to 13,400 per microliter. The patient’s thyroid, renal, electrolyte, acid base and liver function tests were within normal limits. He was referred to admission to the general medicine service along with broad-spectrum intravenous (IV) antibiotic coverage (vancomycin and piperacillin/tazobactam) to empirically treat methicillin-resistant Staphylococcus aureus (MRSA), other gram-positive, gram-negative and anaerobic organisms that might be causing the wound infection. The IV antibiotics were given for about 72 hours till the wound cultures were finalized and the blood cultures resulted negative. The wound was also evaluated by general surgery service who recommend topical wound care and management with antibiotics.
With the intention to treat the underlying disease, we investigated his psychiatric history in detail. He was under the care of a few psychiatrists for a diagnosis of OCD over the last 30 years or so. He was on a variety of different medications for his OCD including aripiprazole, risperidone and fluoxetine. He did not report a great benefit from any of these medications. Apart from the history of smoking, he denied alcohol or substance abuse. He denied any suicidal attempts. He noticed that his skin picking would get worse whenever he gets nervous or anxious. He reported that his mother and sister also had similar obsessive compulsive traits. When he started realizing that his symptoms were getting worse of late and when the medications did not seem to help, he decided to join a few online support groups on the internet. He felt relieved talking to others with similar symptoms and dedicated some time every day talking and listening to them and understanding what medications and therapies helped them.
Once he was ready for discharge from the hospital, he was sent home with prescriptions of a seven-ay course of trimethoprim/sulfamethoxazole double strength and a higher dose of quetiapine (200 mg oral daily). He was referred to the hospital's CBT program that specializes in treatment of OCD and anxiety disorders.


A 26-year-old woman with family history of hypothyroidism on her mother side was referred to our endocrine clinic because of clinical hypothyroidism and a thyroid hot nodule (). After hypothyroidism diagnosis, the thyroid hormone replacement (500 micg/week) has been started and a thyroid sonography requested due to the feeling of lump in the neck by the patient. The ultrasonography findings were an enlarged thyroid gland with diffusely hypo echogenic pattern and heterogeneous echo texture. A 13*6 mm solid isoechoic nodule with regular and sharp margin has been detected in the thyroid isthmus without significant lymphadenopathy. Her first physician had requested a sonography guided fine needle aspiration cytology (FNAC) from the thyroid nodule. The cytology showed a hyper cellular smear containing monolayer sheets, nests, micro follicles and mild nuclear follicular cells pleomorphism in addition to pigment laden macrophages and multinucleated giant cell in hemorrhagic and colloid background.
The final cytological diagnosis was “suggestive of thyroid neoplasm”. The patient was referred to our clinic because of hot area in the thyroid gland isthmus (compatible with thyroid nodule) according to 99mTc pertechnetate thyroid scintigraphy report. Residual thyroid tissue had low uptake ().
We requested an I131 thyroid scintigraphy to rule out the false hot nodule report by 99mTc scintigraphy, which confirmed the hot condition of nodule (). So we decreased the thyroid hormone replacement dosage for definitive assurance of the hypothyroidism diagnosis. Three months after reduced drug doses, the TSH level increased to 25 IU/L. Color flow Doppler ultrasonography performed by a thyroid ultrasound specialist revealed a solid hypoechoic nodule of approximately 21*19*9 mm in diameters (compared to first sonography which the nodule was isoechoic and lower in size) with well demarcated margin. Increased blood flow was reported in thyroid nodule periphery in addition to thyroid parenchyma ().
L-T4 substitution therapy was started again with full dose (700 micg/week) and fine needle aspiration (FNAC) was repeated because of increase in nodule size. Cytology report revealed an adenomatous nodule in background of lymphocytic thyroiditis. The thyroid function tests were acceptable in follow-up .The nodule size diminished to 11*5 mm at the four months full dose levothyroxine replacement therapy and disappeared after 8 months follow-up according to sonography report ().


A 13-year-old Caucasian boy presented with reduced vision. There was no family history of consanguinity or nystagmus in family members. His past medical history was unremarkable and he has had slowly progressive myopia in both eyes. His best corrected visual acuity (BCVA) was 0.5 (logMAR) in each eye. He had high myopia with a current refraction—7.5SD/+1.5SC at 60 degrees in both eyes. Clinical examination revealed horizontal jerk nystagmus with no significant head posture. Anterior segment examination was normal with no signs of iris transillumination. Fundus examination showed hypopigmented (blonde) fundi with visible choroidal vasculature and peripapillary atrophy with a mildly hypoplastic optic nerve in both eyes () which was confirmed with magnetic resonance imaging (MRI) of the patient’s brain and orbits.
Spectral domain optical coherence tomography (SD-OCT) showed bilateral foveal hypoplasia, grade 1, displaying presence of the inner plexiform and inner nuclear layers at the fovea with a widened outer nuclear layer (). In addition, the retinal nerve fiber layer showed some thinning, but Goldmann perimetry showed no constriction of either visual field. Fundus autofluorescence showed a reduced foveal reflex but was otherwise normal.
Full-field electroretinography (ERG) examination was done using skin electrodes as the patient did not tolerate corneal ones. Photopic flash and flicker responses (Light Adapted 3.0) were severely attenuated in both eyes. Isolated rod responses (Dark Adapted (DA) 0.01) were also severely attenuated bilaterally. Combined rod cone (DA 3.0) and responses to high flash (DA 10.0) demonstrated normal a-waves (for pad recording); however, b-wave was markedly attenuated giving rise to an electronegative waveform in both eyes, characteristically known as Schubert-Bornschein type ERG. The multichannel pattern onset visual evoked potentials (VEP) demonstrated symmetrical responses and normal responses across right and left occipital recording when each eye was tested independently.
The proband underwent a targeted gene panel for congenital stationary night blindness containing 16 genes (CABP4, CACNA1F, CACNA2D4, GNAT1, GPR179, GRK1, GRM6, LRIT3, NYX, PDE6B, RBP4, RDH5, RHO, SAG, SLC24A1, TRPM1) through the Oxford University Hospitals NHS Foundation Trust Genetic Laboratory at Oxford, UK. Mutation screening was carried out by next generation sequencing with library preparation using the Agilent focused clinical exome +1 kit followed by sequencing on the Illumina platforms. Data were analyzed using an in-house pipeline and virtual gene panels, with all mutations confirmed by Sanger sequencing. The proband was found to have a novel hemizygous splice-site mutation c.4294-11C>G in intron 36 of the CACNA1F gene (hg19; chrX:g.49067563G>C, NM_005183.2:c.4294-11C>G) (). This variant has been predicted to affect the efficiency of the splice acceptor site and lead to aberrant splicing. Parental segregation found that the mother was a carrier of the variant; however, she was clinically asymptomatic with no phenotypic features of CACNA1F-related disease. depicts the family pedigree of the proband.


Here, we report the case of a 3-year-old boy presenting with brownish erythematous scaly plaques in the axillar, popliteal, umbilical, and inguinal regions with diffuse PPK ( and ). At birth, the patient had blisters and erosions, and marked scaling was present on the scalp, flexural and intertriginous areas, palms, and soles. The severity of the symptoms fluctuated over time, occasionally with more severe epidermolysis, fissures, and onychodystrophy. The parents had no relevant history of skin disease.


A 15-day-old female neonate presented to us with breathing difficulty and cyanosis for nine days after a referral from the district hospital. On examination, respiratory rate was 74 breaths/min, marked chest in-drawing, right-sided thoracic bulge with decreased air entry, and stony dull percussion. According to her mother, she was her second child, born in the hospital through normal vaginal delivery. She gave the history of oligohydramnios during the end of the second trimester, diagnosed on routine ultrasound. Otherwise, the delivery was uneventful except delayed cry, appearance, pulse, grimace, activity, and respiration (APGAR) score 6/10 at birth, and cord around the neck. The infant developed breathing difficulty first on the sixth and 12th day of her life after which she was referred and admitted to our tertiary hospital where oxygen saturation was maintained and she was started on intravenous fluids.
Owing to the deteriorating condition of the patient, a laboratory workup for sepsis was done and intravenous antibiotics including Ampicillin (200 mg/kg/day in two divided dose), Amikacin (15 mg/kg/day in two divided dose), Ceftazidime (150 mg/kg/day in two divided dose), and Vancomycin (45 mg/kg/day in three divided dose) were administered. The results of the complete blood picture on the first, second, and third day of admission are elucidated in Table and other baseline lab parameters are shown in Table .
Chest X-ray revealed right hemithorax with a mediastinal shift to the left side. No cystic lesion was noted on X-ray; therefore, it excluded the Bochdalk Hernia (on the left side) and Morgani Hernia (on the right side). Figures , show a chest X-ray before and after pleural tap, respectively.
The pleural fluid analysis showed protein 2.6 g/dl, total cell count 680/mm, red blood cell 10-15/HPF, neutrophil 40%, lymphocyte 60%, no gram staining, and acid-fast bacilli (AFB) was noted. The second pleural tab revealed greenish fluid suggesting empyema. Chest intubation drained around 250 ml fluid. Computed tomography (CT) showed bilateral pleural effusion, pneumothorax, and subcutaneous emphysema on the right side while moderate pleural effusion was noted on the left side (Figure ).
Based on the above investigations, a diagnosis of neonatal spontaneous chylothorax was made. Arterial blood gas (ABG) showed respiratory acidosis and hypoxemia. The infant was intubated, and even after mechanical ventilation, the respiratory rate got worsened. The condition of the neonate continued to deteriorate and she expired on the 23rd postnatal day.


A 34-year-old woman was first referred to our Center in February 2015 for having experienced multiple abnormal gestations. At that point she was 8 weeks pregnant.
Based on medical records and her personal dictation, we combed through the couple's complete medical history and illustrated in a pedigree diagram (). They had eight previous pregnancies in total: In August 2005, missed abortion occurred at the eighth gestational week of their first pregnancy. In October 2006, it was diagnosed that the second pregnancy was an ectopic pregnancy on the left fallopian tube, whereupon transabdominal resection of the left fallopian tube was performed. In October 2007, July 2008, August 2010, and December 2012, the couple went through four missed abortions or miscarriages, all of which occurred between 8 and 16 gestational weeks. In November 2013, the fetus of their seventh pregnancy was diagnosed with thickened nuchal translucency (NT), right abdominal fissure and visceral valgus. Induced labor was performed at 15 weeks of gestation.
In 2015, all indicators of their 8th pregnancy during early pregnancy were normal, including serological screening, NIPT (non-invasive prenatal testing) results. However, at 17th week of gestation, ultrasonic examination revealed that the fetus had extremely short limbs and bowing of long bones (). Amniocentesis and subsequent prenatal diagnosis with chromosomal karyotyping and micro array (CMA) were conducted. However, no variation with clinical significance was identified. The fetus was aborted at 20 gestational weeks.
In April 2018, we performed prenatal diagnosis for their most recent pregnancy at the 16th week of gestation. Ultrasonography indicated that bilateral lower limbs of the fetus were shortened, not excluding the presence of bending (). Besides regular prenatal genetic testing as described above, whole-exome sequencing was also introduced after induction.


A 60-year-old man visited another hospital because of left scrotal enlargement. The testis was swollen and stiff on palpation, and ultrasound demonstrated a mosaic echoic mass. Blood examination showed an elevated human chorionic gonadotropin concentration of 6418 mIU/mL (reference range, <0.5 mIU/mL), elevated alpha-fetoprotein concentration of 3534.7 ng/mL (reference range, 7–10 ng/mL), and normal lactate dehydrogenase concentration of 189 U/L (reference range, 106–211 U/L). Contrast-enhanced CT showed normally sized lymph nodes and a double IVC. Left high orchiectomy was performed, and the pathological diagnosis was non-seminoma pT2 (60% embryonal carcinoma, 20% yolk sac tumor, and 20% immature teratoma) with vascular invasion. The patient’s tumor markers did not normalize postoperatively, at which point he was referred to our hospital. Blood examination in our hospital showed a human chorionic gonadotropin concentration of 46.4 mIU/mL, alpha-fetoprotein concentration of 59.9 ng/mL, and lactate dehydrogenase concentration of 141 U/L.
CT performed 1.5 months after the initial CT examination revealed swollen lymph nodes in the para-aortic region (under the left renal hilum, at the bifurcation of the inferior mesenteric artery). The clinical diagnosis was left testicular cancer T2N1M0S2, Stage IIA according to the Japanese Urological Association; the prognosis was considered to be good according to the International Germ Cell Consensus Classification. After four courses of chemotherapy with etoposide and cisplatin, the tumor marker levels decreased to the reference range and the swollen lymph nodes decreased to a maximum diameter of 1.0 cm. Therefore, we planned to perform RPLND. Because of the double IVC, we used the preoperative CT images to create 3D images using SYNAPSE VINCENT® software (Fujifilm Medical Co., Ltd., Tokyo, Japan) (Fig. ). The 3D images clearly showed that the left iliac vein formed the left IVC, which ascended along the left side of the abdominal aorta and flowed into the left renal vein. No findings of an interiliac vein were identified. Residual lymph node masses were located under the left renal hilar region and at the bifurcation of the inferior mesenteric artery, and these lymph node masses were in contact with the left IVC. Because anomalous lymphatic drainage associated with the double IVC was highly suspected, we decided to extend the template of the dissection range to include the right side of the right IVC (Fig. ). Intraoperative examination revealed that the residual lymph node masses were in contact with the aorta and left IVC, as the 3D images indicated, and that severe adhesion with the surrounding tissues was absent (Fig. ). The operation time was 5 h 40 min, and the intraoperative blood loss was 1112 mL. The postoperative course was uneventful, and the patient was discharged from our hospital on postoperative day 14. The surgical specimen included a teratoma component, and no recurrence was observed during 17 months of follow-up.


The patient is a 20-year-old female who presented to the emergency department (ED) with the complaint of a diffuse whole-body rash. Her past history was notable for depression as she was recently prescribed lamotrigine two weeks prior to ED presentation. She was recently discharged from another hospital two days ago where she was hospitalized for three days due to complaints of blistering of her lips, sore throat, and mild rash on the extremities. She was given the diagnosis of hand-foot-mouth disease and was treated with 1 gram of ceftriaxone. She reported a decrease in the severity of sore throat upon discharge from ED but the rash continued to progress and had spread throughout most of her body parts. The lamotrigine was subsequently discontinued by the primary care physician. She decided to present to the emergency department (ED) for further evaluation.
In the ED, she had a temperature of 102.4 F, blood pressure of 152/67 mmHg, heart rate of 120, and a respiratory rate of 22 per minute with an oxygen saturation of 98%. Physical examination was notable for a young female appearing uncomfortable with a diffuse maculopapular erythematous rash with scattered bullae lesions covering approximately 36% of her body surface area (Figure , ). Her lips were blistered with erythematous mucus membranes as well as erythema with erosions of the eyes (Figure ). The Nikolsky's sign was not appreciated. The rest of the physical examination was unremarkable. The laboratory data were unremarkable for signs of active infection given no leukocytosis and sterile blood cultures. Acetaminophen 1 gram was administered orally for fever and she was resuscitated with intravenous fluids. The patient was admitted to the progressive care unit for closer hemodynamics monitoring and supportive care. She was then transferred to a tertiary level burn care center within the next few hours for the continuation of care. She was diagnosed with toxic epidermal necrosis. She was monitored closely and received supportive management in the burn unit. The patient was subsequently discharged home in one week.


A 35-year-old female presented with constant pelvic pain suggesting pelvic congestion syndrome. Magnetic resonance imaging revealed dilation of the left ovarian vein and vessel embolisation was indicated. Figure (a-c) shows the anatomy of the left ovarian vein upon catheter-based venography, i.e., two twisted branches, each 5–6 mm in diameter. The patient also had a nickel allergy discovered through allergy tests for skin reactions after wearing bracelets and rings. While rare, reactions to implanted devices in patients with metal allergies (including nickel) exist in the literature (Fahrni et al. ; Stamm et al. ; Clague et al. ). Furthermore, the metallic content of endovascular devices is not always apparent (Univers et al. ). Therefore, the use of a shape memory polymer vascular plug was considered a reasonable strategy to minimise the potential of an allergic reaction to implanted metallic embolic material in a patient with a known hypersensitivity, and especially in an ovarian vein case, where a large amount of embolic material is often implanted. The IMPEDE-FX Embolization Plug is comprised solely of a shape memory polymer plug and a platinum/iridium proximal marker. Figure shows the dimensions of the plug used in this case (IMP-FX-12). The volume of the shape memory polymer material in this size is approximately 1.25 mL. The left ovarian vein was accessed with a 90 cm 5 Fr Flexor Ansel Guiding Sheath (Cook Medical, Bloomington, Indiana, USA) and a 0.035 Radifocus Guidewire M (Terumo Corporation, Tokyo, Japan) using standard techniques via the right femoral and left renal vein. The first ovarian vein branch was accessed and the first IMPEDE-FX Embolization Plug was pushed into the vessel just proximal the vessel twist. The twist in the vessel branch minimised the likelihood of reflux-induced distal (caudad) device migration while the shape memory polymer was undergoing initial expansion. The catheter was retracted 3–4 cm from the device to allow blood flow into the vascular plug structure and to deliver contrast injections without putting unnecessary pressure on the vessel. Holding the catheter in place also mitigated any potential proximal (cephalad) migration risk, although this was not observed. Approximately 10 minutes later, and after initial expansion of the first plug was confirmed by contrast injection, a second shape memory polymer plug was deployed into the same branch just proximal to the first. Again, expansion was confirmed prior to removing the catheter in order to mitigate any potential proximal migration risk. The other branch was accessed and two more shape memory polymer plugs were deployed with a similar technique.
It was not necessary to embolise the trans-pelvic varices with sclerosant. No other embolic material was used in the treated vessels. Ten minutes after deployment of the fourth plug, plug expansion was confirmed by contrast injection and the case was finished using standard techniques. Figure shows the final case image. Follow-up magnetic resonance imaging at 4 months post procedure showed a sustained occlusion of the treated vessels and the patient showed no signs of allergy to the implanted material.


An 84-year-old female with PMHx significant for HTN, IDDM, HFpEF, CAD s/p PCI w/DES, CKD, presented to the hospital with syncope. There was no head trauma, seizure activity, tongue biting or urinary/fecal incontinence per daughter, who witnessed the episode. At baseline, the patient has dyspnea on exertion, orthopnea, PND and lower extremity swelling bilaterally. She had endorsed abdominal discomfort for multiple days prior to the event. There were no recent sick contacts or recent travel and she denied cough, fever, chills or diarrhea.
In the Emergency Department (ED), initial blood pressure was stable with a HR of 50 bpm. Her cardiovascular exam was unremarkable and the respiratory exam was notable for inspiratory crackles at the bases bilaterally. Initial labs were pertinent for mildly elevated inflammatory markers (). She received IV lasix and required 2 L/min of nasal cannula to maintain adequate SpO2. A chest radiograph showed a small left-sided pleural effusion. Nasopharyngeal PCR was positive for COVID-19.
An electrocardiogram (EKG) confirmed sinus bradycardia, HR 45 bpm with no AV-node dysfunction (). Transthoracic echocardiogram (TTE) on admission demonstrated an ejection fraction (EF) of 60%, no wall motion abnormalities and mild aortic stenosis (AS). Cardiac enzymes negative x2. Coronary angiogram from 2014 showed single vessel thrombotic occlusion of the marginal branch of the right coronary artery (mRCA).
On day 3 of hospitalization, she developed worsening renal failure and hypoxemia, requiring 6L of oxygen via nasal cannula to maintain O2 saturation. Telemetry monitoring continued to show persistent sinus bradycardia with a nadir of 40 bpm. At this time, the patient remained afebrile, hemodynamically stable. Electrolytes and thyroid stimulating hormone (TSH) were within normal limits. All atrioventricular (AV) nodal blocking agents were held. No ST segment changes or T-wave abnormalities were identified on serial EKGs and cardiac biomarkers remained negative.Additionally, the patient never endorsed any chest pain or pressure during the hospital course.
Given the persistent sinus bradycardia recorded on cardiac telemetry, a decision was made to undergo an electrophysiology (EP) study which revealed a delayed sinus node recovery time (), confirming SND. Subsequently, a dual chamber permanent pacemaker (PPM) was successfully placed without complications. Upon further evaluation, she was recommended for subacute rehab (SAR) with outpatient cardiology follow up.


A 56-year-old man complained of sudden epigastric pain and was transferred to the emergency department. He had undergone partial resection of the small intestine for leiomyosarcoma 25 years previously at another hospital (31-year-old). He had an unremarkable family history, except for a father with aplastic anemia. He consumed alcohol occasionally and had never smoked.
On admission, vital signs included a blood pressure of 108/65 mmHg, a pulse rate of 112 beats/min, a respiratory rate of 12 breaths/minute, and an oxygen saturation of peripheral artery (SpO2) 98%. Tenderness was noted in the epigastric region, but no signs of peritoneal irritation were seen. Diminished peristaltic sounds were noted. Blood tests showed a total bilirubin of 3.9 mg/dL, aspartate transaminase (AST) of 283 U/L, alanine aminotransferase (ALT) of 301 U/L, alkaline phosphatase (ALP) of 1400 U/L, and gamma-glutamyl transpeptidase (γGTP) of 324 U/L, indicating hepatobiliary dysfunction, with a hemoglobin (Hb) level of 10.2 g/dL, suggestive of anemia. Tumor markers (alpha-fetoprotein [AFP], protein induced by vitamin K absence or antagonist-II [PIVKA-II], carcinoembryonic antigen [CEA], and carbohydrate antigen 19-9 [CA19-9]) were all within the normal range. The patient was negative for hepatitis C virus antibodies (HCVAb) and hepatitis B surface antigen (HBsAg).
Abdominal computed tomography (CT) showed an irregular high-density lesion in the center of the liver, and bleeding was suspected. A multiple mass with contrast effects was observed in the left lobe of the liver, which was considered to be a tumor-associated hemorrhage (). Diffusion-weighted magnetic resonance imaging (DWI-MRI) of the abdomen also revealed multiple tumors with reduced diffusion in the left lobe. On magnetic resonance cholangiopancreatography (MRCP), the intrahepatic bile duct was markedly compressed due to the bleeding (). Upper and lower endoscopy and capsule endoscopy were performed, but no neoplastic lesion including submucosal tumor was found in the digestive tract.
As the central part of the liver was diagnosed with a giant hemorrhage from tumor, ultrasound-guided percutaneous biopsy was performed for the 15-mm hepatic tumor in segment 2 (). Pathological findings revealed proliferation of spindle-shaped atypical cells, and immunostaining for c-kit and CD34 were both positive; the patient was therefore diagnosed with GIST. The MIB-1 labelling index was 2% (). The atypical mitotic figure was 2/50 high-power fields (HPF). A mutation was found in Exon 11 in the C-kit gene search. Since the last operation was 25 years ago, the case was closed, and no pathological specimens from that time were available for analysis. The size of the small intestinal tumor was unknown, because his medical record was not available. However, based on patient history and clinical course, the patient was diagnosed with GIST with metastasis to the liver 25 years after the initial surgery.
Imatinib (400 mg/day) was introduced; however, 8 days after the initiation, the patient complained of sudden abdominal pain. Abdominal CT revealed intra-abdominal bleeding due to massive bleeding from the GIST liver metastases. Emergency transcatheter arterial embolization (TAE) was performed, and hemostasis was achieved.
We considered the possibility that Imatinib might have triggered the tumor bleeding. However, since the mutation in Exon 11 is a high-response marker for imatinib, the drug was reintroduced after informed consent. Ten days after treatment re-initiation, intra-abdominal hemorrhage was observed again. Because of acute renal failure, the patient was treated for 6 days in the intensive care unit. It was decided that imatinib could not be continued, and the patient was therefore started on sunitinib after improvement of his general condition (57-year-old).
Because of hand-foot syndrome, liver dysfunction, and cytopenia, sunitinib (50 mg/day) was administered for 1 week, followed by 2–4 weeks off treatment. Stable disease (SD) was maintained until the 50th course, and no bleeding complication was observed. However, progressive disease (PD) was observed when evaluating CT images after 58 courses (liver metastases were clearly increased in size), and we switched the patient to regorafenib (120 mg/day), which is the third line of chemotherapy (62-year-old). The patient achieved SD after 10 courses of regorafenib therapy for one week and resting for 2–4 weeks. However, CT imaging revealed apparent PD after 19 courses (liver metastasis increased rapidly, although no metastases were seen in other organs), the chemotherapy was discontinued, and palliative treatment was administered for next one year. Seven years after the diagnosis of liver metastasis, he died of multiple organ failure due to GIST () (63-years-old).
Autopsy was performed with the consent of his family. The liver weighed 6,300 g and was markedly swollen. Macroscopically, a tumor mass with hemorrhagic necrosis was found throughout the liver, with only a small amount of normal liver tissue remaining (). Pathologically, spindle-shaped tumor cells similar to those observed on liver biopsy were observed. The tumor cells were c-kit- and CD34-positive, and the diagnosis of GIST was confirmed. The MIB-1 labelling index was 13%, and the atypical mitotic figure was 13/50 HPF (). A 4-cm tumor was found on the terminal ileal serosa. Pathologically, it was diagnosed with peritoneal dissemination of GIST (). Although macroscopic findings of lungs did not indicate a clear tumor, multiple minute lung metastases of GIST were observed in all lung lobes microscopically (). No metastases were observed in other organs both macroscopically and microscopically.


A 10-year-old female was brought to the emergency department complaining of a 7-day history of low-grade fever up to 38.5 °C, sore throat, mild cough, sharp abdominal pain, mainly in the right abdominal area, and nausea. Physical examination revealed sensitivity to palpation in the right hypochondriac and lumbar regions and epigastrium, normal bowel sounds, and no abdominal distention.
Additionally, bilateral cervical and axillary lymphadenopathy, tonsillar hypertrophy without exudates, and a palpable hepatosplenomegaly were noticed, and there was no conjunctival icterus.
Laboratory studies showed a white blood cell count of 7200 × 103 per microliter (μL) (4.5–14.5 × 103/μL), a C-reactive protein level of 16.2 milligrams per deciliter (mg/dL) (3–5 mg/dL), a total bilirubin level of 29 μg/L (0–17 μg/L) with direct bilirubin of 10 μg/L (0–6 μg/L), an alkaline phosphatase (ALP) level of 642 units per liter (U/L) (35–110 U/L), gamma-glutamyl transferase (GGT) levels of 297 U/L (1–48 U/L), glutamic-pyruvic transaminase (GPT) levels of 301 U/L (1–31 U/L), and glutamic-oxaloacetic transaminase (GOT) levels of 279 U/L (1–31 U/L).
Formal abdominal ultrasonography revealed a thickening of the gallbladder wall (4.5 mm) and pericholecystic edema (). Distention of the gallbladder was not evident, and no stones or dilatation of the biliary tract were reported. Based on these findings, the diagnosis of acute acalculous cholecystitis was made and the patient was admitted to the pediatrics department for further investigation and treatment.
The patient was treated with fasting and intravenous rehydration. Her cardiovascular and respiratory function remained stable. Blood and urine cultures were negative. Serological tests, both heterophile antibody test and IgM antibodies against EBV capsid antigen, confirmed the diagnosis of infectious mononucleosis. Serological tests for hepatitis A, B, C, CMV, HIV, and Toxoplasma gondii were negative.
Two days after admission, the patient had a good clinical status, fever was resolved, enteral nutrition was restarted, and the abdominal pain had also disappeared. In the laboratory test on day 3, a total bilirubin (B) level of 19 μg/L with direct bilirubin of 7 μg/L, an alkaline phosphatase (ALP) level of 199 units per liter (U/L), gamma-glutamyl transferase (GGT) levels of 48 U/L, glutamic-pyruvic transaminase (GPT) levels of 19 U/L and glutamic-oxaloacetic transaminase (GOT) levels of 22 U/L were observed.
The patient was discharged on day 4 with a good clinical status. Two weeks later, a clinical control in the outpatient department revealed no clinical or laboratory abnormalities and an abdominal ultrasound revealed a total remission of the previous abnormal findings.
After 6 months of follow up, the patient remains asymptomatic.


The patient is a 57-year-old multiparous woman who presented to her primary care physician with complaints of abdominal pain and bloating. Imaging demonstrated an 8 cm complex adnexal mass with omental thickening, peritoneal carcinomatosis and ascites. CA-125 was elevated (928). She underwent an optimal primary tumor reductive surgery including total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic lymph node dissection, omentectomy, and Argon laser ablation of tumor deposits on the mesentery. Intra-operatively, she was found to have tumor involving bilateral tubes and ovaries, the mesentery of the rectosigmoid, epiploica and omentum. Intra-operative frozen section was consistent with serous carcinoma. Final pathology demonstrated low-grade serous carcinoma of the ovary, arising from a serous borderline tumor, FIGO stage IIIC.
The patient was offered standard of care adjuvant chemotherapy followed by hormone therapy maintenance, versus participation in clinical trial comparing this regimen to hormone therapy. She elected to proceed on clinical trial (GY-019) and was randomized to a regimen of letrozole 2.5 mg daily for 6 cycles, followed by letrozole maintenance. Her post-operative CA-125 declined to 52. A CT scan prior to initiating therapy showed ill-defined nonspecific peritoneal thickening in the pelvis.
Less than two months following the primary tumor reductive surgery (and one week after starting adjuvant letrozole therapy), the patient presented with a sepsis-like picture including fever, abdominal pain and distention, and leukocytosis. Repeat imaging showed ascites and progression of peritoneal nodules in the pelvis. She was started on broad-spectrum antibiotics however her clinical condition deteriorated. Physical examination was concerning for peritonitis and she was taken to the OR for exploratory laparotomy. Intraoperative findings included loculated, non-purulent ascites and edematous bowel without evidence of perforation. Microbial cultures of the ascites fluid were negative. Biopsies of soft tissue nodules along the mesentery and small bowel nodule revealed a high-grade malignant neoplasm with epithelioid and spindle cell morphology. The tumor cells were weakly positive for pancytokeratin (AE1/AE3) and strongly positive for CAM5.2. Patchy staining with desmin and SMA were also observed. The combined morphologic and immunohistochemical findings were consistent with a sarcomatoid/anaplastic carcinoma. This prompted review of her original pathology, and a microscopic focus of sarcomatoid/anaplastic carcinoma was identified in the right ovary ().
She was started on chemotherapy (carboplatin and paclitaxel) and initially demonstrated dramatic clinical improvement. Unfortunately, she was diagnosed with progressive disease after 4 cycles of chemotherapy and died of disease 7 months after her initial diagnosis.


A 25-year-old male with a history of well-controlled gastro-esophageal reflux disease (GERD) presented to the emergency room for evaluation of one week of severe odynophagia and inability to tolerate po. He had been treated with a proton-pump inhibitor (PPI) for several years with good effect. Approximately 2 months prior to presentation, he started vaping tetrahydrocannabinol (THC) and nicotine with recent heavy daily use. He denied any alcohol or NSAID intake. On physical exam, the patient was non-toxic appearing with a soft abdomen.
We performed esophagogastroduodenoscopy that revealed Los Angeles Grade C esophagitis (involving ≥ 1 mucosal breaks continuous between tops of ≥ 2 mucosal folds, < 75% circumferential) (Fig. ). Histopathological analysis of esophageal biopsies demonstrated granulation tissue with acute and chronic inflammation (Fig. ). Periodic acid-Schiff-diastase staining was negative and immunohistochemical stains for herpes simplex virus and cytomegalovirus were negative. There was no evidence of eosinophilic esophagitis. He was diagnosed with esophagitis secondary to vaping. We treated him with intravenous 40 mg twice daily PPI and analgesics until he was able to tolerate oral intake. He was counseled extensively on vaping cessation. The patient reported complete resolution of symptoms after 2 months of PPI therapy and vaping cessation.


A 44-year-old man was admitted for surgery due to soft tissue sarcoma of his left hip. Since the tumor was very large with a diameter of 30 cm and invaded the surrounding tissues, he had received the neoadjuvant chemotherapy (epirubicin 60 mg/m2 day 1, every 2 weeks) after the admission. Severe abdominal pain with diarrhea and vomiting were the complaints 3 days after the initiation of the second cycle of chemotherapy. There were no jaundice, abdominal distension, melena, and hematochezia. Physical examination revealed diffuse abdominal tenderness with mild rebound tenderness and guarding. Mild fever (37.6°C) and tachycardia (125 beats/min) were also demonstrated. Laboratory test results revealed remarkable neutrophilia (WBC 33.22 × 109/L, Neutrophils: 98.4%) with normal bilirubin. The examination of stool showed no white blood cells. Computed tomographic images (CT) showed air in the portal () and mesenteric vessels (, arrow) and dilated bowel loops. One part of edematous small intestine (, arrow head) without obvious pneumatosis intestinalis was also noticed. No thrombus was identified in the CT scan. As the differential diagnosis was intestinal necrosis, the necessity of surgery was told to the patient and his relatives. After obtaining their informed consent, an exploratory laparotomy was performed. However, nothing abnormal was detected, except for swollen small intestine from 100 to 150 cm distal to the Treitz ligament with a little ascites. No evidences of inflammation, including hyperemia of intestine and fibrous exudation of serosa, were detected on the segment of the swollen bowel, and its mesentery was normal with palpable pulses. The patient had a rapid recovery after operation, treated by antibiotics and parenteral nutrition. A follow-up CT scan showed complete resolution of portal vein pneumatosis 18 days after the exploratory laparotomy. Finally, the patient received left hemipelvectomy with the help of a temporary balloon occlusion of abdominal aorta successfully 20 days after the exploratory laparotomy. The post-operative pathological report showed that the tumor was high-grade sarcoma (unspecified/undifferentiation), and the immunohistochemical staining demonstrated PCK (+/±), EMA (–), eight factor (–), CD34 (–), CD31 (–), Fli-1 (–), INil (+), desmin (–), SMA (–), S-100 (–), and P53 (+) in the tumor cells. Three months later, the patient received interventional embolization of the branches of the bilateral internal iliac artery and radiotherapy to the tumor. However, the patient died from tumor progression 4 months later. During the period from exploratory laparotomy to his death, he had normal diet, and suffered no abdominal pain and symptoms of digestive tract. shows the timeline with relevant data from the episode of care.
The patient's written informed consent was waived due to the retrospective nature, and the patient information was anonymized.


A 32-year-old female from a remote hilly village presented with an 8-week history of progressive swelling around the nose, and severe bouts of headaches. For the last 2 weeks, she was also experiencing episodes of recurrent epistaxis, diminution of vision, and double vision. According to her husband, the disease had rapidly progressed in the last 4 weeks leading to severe facial disfigurement and now it had become difficult to recognize her. She was unable to do household chores and self-care, being mostly confined to bed. On examination, the patient had a swelling involving the whole of the nose with facial puffiness and proptosis of the right eye. The right vestibule of the nose was full of some necrotic appearing mass. Bilateral level I and II neck nodes were enlarged. She had marked anhedonia and was chair-bound, not responding to any queries.
A contrast-enhanced magnetic resonance imaging (MRI) of the brain and neck revealed a multi-lobulated lesion of size 8.2 × 4 × 6.5 cm involving the right nasal cavity. The lesion was reaching anteriorly up to the external nare with infiltration into the upper lip, bilateral gingivobuccal sulcus, right masticator space, hard palate, and projecting posteriorly into the nasopharynx (Figure , panel A). It had completely destroyed the nasal septum, turbinates, and cribriform plates with extension into the bilateral orbit and infiltrating into the medial rectus muscle and optic nerve. It had displaced the right globe and resultant proptosis. There was evidence of invasion of frontal dura, sphenoid sinus, and pituitary gland. Imaging of the thorax and abdomen and a bone scan revealed no evidence of metastasis.
Her blood counts, liver, renal, coagulation, and the metabolic panel were within normal limits. A biopsy from the right nasal cavity mass was obtained and it showed a lobulated tumor composed of nests of cells with scanty to moderate cytoplasm with round to oval nuclei dispersed in a neurofibrillary stroma (Figure ). Tumor cells were immune positive for pan-CK and chromogranin while they were negative for p40. Ki-67 labeling index was 70%.
A final diagnosis of ONB, Kadish stage D, Hyams grade III was reached.
Her case was discussed in the multidisciplinary tumor board. Since it was very difficult to achieve an R0 resection without much morbidity and neurological deficits, neoadjuvant chemotherapy (NACT) was planned. However, in a patient with poor performance status (PS) and severe depression, it was difficult to administer chemotherapy. The patient's husband was counseled in detail regarding the guarded prognosis and pros and cons of chemotherapy and he consented for the treatment.
Tumor lysis prophylaxis in the form of allopurinol was given. We administered a 3-day protocol of cisplatin (25 mg/m2) and etoposide (75 mg/m2); however, the dose was reduced by 15% keeping in view the poor PS of the patient. There was a striking improvement in signs and symptoms. Her epistaxis and headache resolved on day 7 post-chemotherapy. Visual acuity improved and the double vision disappeared by day 10. On day 14, facial swelling and proptosis resolved, and PS started improving (Figure ). Depression was resolved completely by the end of the first cycle of chemotherapy.
The dose of chemotherapy was optimized and she received four cycles of the same protocol without any significant adverse effects. MRI done for response evaluation after four cycles was suggestive of a very good response to therapy (Figure , panel B). She was referred to the head and neck surgeon for surgical management. The patient underwent an endoscopic craniofascial resection of the tumor via modified Denker's approach. Intraoperatively, pinkish, polypoidal soft tissue mass in the right nasal cavity and b/l maxillary, ethmoid, sphenoid sinus with obliteration of frontal recess with mucocele formation was noted. Bony dehiscence was noted over ipsilateral lamina papyracea, cribriform plate, planum sphenoidale, and optic nerve and suprachiasmatic region, however, dura and periorbita were found intact. The tumor was excised in piece meal using debrider and coblation. The soft tissue adherent to the cribriform region and planum was sent for the frozen section, which was negative. The peri-operative period was uneventful. There was no neurological deficit. Post-operative histopathological examination of the resected tumor mass was suggestive of pathological complete response. She received two more cycles of the same protocol as the adjuvant therapy and subsequently referred to the radiation oncologist for adjuvant radiation therapy.


A 61-year-old male presented to us with a lump on his lower part of back of 4 weeks' duration. The lump was rapidly increasing in size with mild pain. He denied similar lesions elsewhere. On examination, there was an ill-defined swelling in the lower part of the back, fixed to the skin and the underlying tissues. The Zubrod performance status (PS) was zero. An incisional biopsy of the lesion was done, which was suggestive of intermediate to large size round tumors cells arranged in sheets with interspersed histiocytes, infiltrating into the dermis and subcutaneous tissue suggestive of lymphoma. Immunohistochemistry (IHC) markers were ordered, and a positron emission tomography-computed tomography (PET-CT) scan was advised. PETCT was suggestive of a 6.8 × 4 cm cutaneous-subcutaneous lesion with an SUV max of 22.5 situated at the lower back at the level of L4-L5 vertebra. No other hypermetabolic focus was noted in the rest of the visualized body. On IHC, tumor cells were positive for CD 20, BCL2, BCL6, and MUM1 while being negative for CD3, MYC, and CD10. The Ki-67 labeling index was 60%.
Serum lactate dehydrogenase (LDH) levels were 157 U/L (range). Blood counts including peripheral smear, tumor lysis panel, and liver function tests were normal. Viral marker panel for hepatitis B, hepatitis C, and HIV was negative. No atypical cells were seen on bone marrow examination. A final diagnosis of PCDLBCL, leg type stage IE, non-germinal center B, CNS International Prognostic Index (CNS-IPI) risk low, was reached.
The patient was planned for R-CHOP protocol chemo-immunotherapy. CNS prophylaxis was not given because of low CNS-IPI risk. He received 4 cycles of chemotherapy without any untoward incident. A PET-CT done on day 14 post fourth cycle, was suggestive of partial metabolic as well as a morphological response. Further, 2 cycles were advised.
He reported to us 2 days before the 5th cycle with a 3-days history of headache, inability to close the eyes, and drooling of liquids from both angles of the mouth (Figure ). On examination, he had bilateral lower motor neuron facial nerve palsy. Zubrod PS was preserved. The rest of the clinical examination was non-contributory.
Contrast-enhanced magnetic resonance imaging of the brain was negative for any intra-cranial lesion and leptomeningeal enhancement. Complete blood counts, metabolic panel, liver function, kidney function, and coagulation studies were normal. He was admitted to the day-care and a diagnostic lumbar puncture was done, and cerebrospinal fluid examination (CSF) was ordered. CSF examination revealed elevated proteins (139 mg/dL) and increased total cell count (140/μL) with a lymphocytic predominance. Infiltration by atypical lymphoid cells was seen, ruling a diagnosis of leptomeningeal metastasis from PCDLBCL, leg type (Figure ).


A 51-year-old woman with a medical history of cholecystectomy and beta thalassemia trait presented to the emergency department because of severe epigastric pain during the last 3 days. The patient reported findings of high hematocrit levels in the previous months (Hct ≈ 48%) without any further evaluation and episodes of pruritus in her extremities and trunk during the last 7 months. The initial blood tests revealed an elevated Hct level of 44.8% with Hgb levels of 14.4 g/dl, a white blood cell (WBC) count of 4.81 × 109/L – with 55% neutrophils - and a platelet (PLT) count of 227 × 109/L. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were markedly elevated, while alkaline phosphatase (ALP) and gamma-glutamyltransferase (γGT) were significantly elevated. The other biochemical markers were within normal limits (Table ).
Initial investigation with an abdominal ultrasound showed liver and spleen enlargement (17.5 cm and 15 cm, respectively), with grade 1 ascites, whereas a Computed Tomography (CT) scan revealed multiple liver, spleen, and left kidney infarctions (Fig. a). Splenic or portal vein thromboses were not found. A transthoracic echocardiogram revealed no additional findings. Furthermore, an upper endoscopy identified the presence of portal hypertensive gastropathy. The serum ascites albumin gradient (SAAG) was 1.7 g/dl, compatible with portal hypertension.
An autoimmune inflammatory disorder panel showed that antinuclear antibodies (ANA) and anti - extractable nuclear antigen (ENA) - La antibodies were positive. Thrombophilia workup revealed homozygosity for the C677T MTHFR (methylene-tetrahydrofolate-reductase) gene mutation with normal blood homocysteine levels (Table ).
A whole blood allele-specific polymerase chain reaction (PCR) analysis showed that the patient carried the JAK2V617F mutation. The serum erythropoietin (EPO) level was within normal range (Table ). A bone marrow biopsy revealed a hypercellular bone marrow (90%), with erythroid hyperplasia, mild dyserythropoiesis, mild granulocytic hyperplasia with no dysplastic features and no increase in the blast count (Fig. b-c). Considering all the above the patient was diagnosed as having masked PV complicated with multiple visceral thromboses.
The patient was initially treated with hydroxyurea at 500 mg qd po and enoxaparin at a dose of 1 mg/kg subcutaneously (SC) q12h which corresponds to 6000 IU q12h according to the patient’s weight. A mild decrease of the Hct, AST, ALT, γ-GT, and ALP was initially observed before a second rise during an episode of abdominal pain and ascites causing marked abdominal distension 3 weeks after therapy introduction (Table ). Radiological reassessment with an abdominal CT angiography detected thrombosis of the hepatic veins and a liver biopsy was performed which was consistent with the diagnosis of Budd – Chiari syndrome (Fig. d-e). A peripheral blood flow cytometry analysis was performed, revealing a 91.8% of granulocytes, 45.5% of monocytes and 90.6% of erythrocytes CD55 and CD59-deficient population, suggestive of PNH. The patient’s history did not reveal any indications of hemolytic anemia and associated symptoms, such as fatigue, jaundice, or urine discoloration. At the time of diagnosis, the reticulocyte count, haptoglobin, and indirect bilirubin level were within normal range. A direct antiglobulin (Coombs) test was negative and urine samples were negative for hemoglobin or hemosiderin.
Because of suboptimal response to enoxaparin and hydroxyurea, enoxaparin was switched to acenocumarol, while, due to the appearance of large PNH clones, initiation of complement inhibition treatment with eculizumab was decided. Before eculizumab initiation, the patient was vaccinated with a serogroup B meningococcal vaccine.
After 2 months on hydroxyurea, acenocoumarol, and eculizumab the Hct and Hgb levels decreased, cholestatic enzyme levels were markedly improved, and the liver enzymes were within normal range. Ascites and abdominal pain completely resolved. The laboratory findings after 10 months of treatment are listed in Table .


An 81-year-old man was referred to our hospital following chest xray which revealed an abnormal shadow, and he was subsequently diagnosed with lung adenocarcinoma cT1bN0M1a (M: PLE) Stage IVA (Figure ).
Examination of the DNA sequence of the EGFR gene revealed an uncommon EGFR L861Q mutation. The patient received treatment with afatinib administered orally (40 mg/day). One month later, Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 2 stomatitis was observed, which improved with afatinib withdrawal. After 10 days of withdrawal, afatanib treatment was resumed at a reduced dose of 20 mg/day. Subsequently, grade 1 skin toxicity was observed. However, the patient continued treatment with afatinib. A partial response to afatinib treatment was noted for 49 months until the primary tumor recurred (Figure ). Treatment with afatinib was continued after disease progression, and he died of bacterial pneumonia 59 months after the initiation of afatinib treatment. The patient provided oral informed consent for the publication of this report.


A 4-year-old girl was considered as having phenylketonuria (PKU) at the age of 1 month due to her less dark pigmented hair and a positive neonatal screening for Phe.
Her condition was confirmed by detecting homozygous mutation of PAH at nucleotide c.331 in exon 3 (c.331T > C) in the patient and heterozygous in both parents. The genetic sequencing was made in Beijing Kangxu Medical Research Center, Haidian District, Beijing, China. She was a term infant with a birth weight of 2700 g. There was no family history of arthritis or PKU. The baby was given a Phe-restricted diet. L-Amino acid-based medical foods (without Phe) provide ~ 80 % of the protein needs. The proportion of modified low-protein food was adjusted according to the concentration of regularly monitored blood Phe. She presented with normal motor development including walking and running, slight language delay and intellectual disability at 2 years old. At the age of 3.5 years, she presented with pain and swelling of her right ankle, right knee, and right hip joint (see Fig. ). At that time, serum Phe concentration was 22.8 mg/dL. Unresolved ankle pain and elevated serum Phe concentration prompted referral to West China Second University Hospital of Sichuan University at the age of 4.5 years. She had severe pain of bilateral ankles, knees, and knuckles. She could not walk or jump. The affected joints were swollen, hot, and painful. A radiograph of the lower limbs showed bone demineralization. Laboratory investigation demonstrated an increase in Phe (19.52 mg/dL reference range: < 1.8 mg/dL), C-reactive protein (33.6 mg/L; reference range: 0-5 mg/L), erythrocyte sedimentation rate (36mm/h; reference range: < 21mm/h), tumor necrosis factor alpha (10.9pg/ml; reference range: <8.1pg/ml), and interleukin 6 (41.87pg/ml; reference range: < 5.9pg/ml), and a positive rheumatoid factor. Liver function, renal function, bone marrow biopsy smear and bone marrow culture were normal. Autoantibodies, antineutrophil cytoplasmic antibodies, anticardiolipin antibody, mycoplasma pneumoniae antibody, HLA-B27, and PPD tests were all negative. She was diagnosed with JIA and treated with a nonsteroidal anti-inflammatory drug (naproxen), methotrexate and low dose prednisone. Her joint pain responded well to the therapy. The patient has had followed-up appointments every 3 months for 1 year. Now she is thriving and can walk normally, with no further complaint of joint pain. Serum Phe concentration has been maintained within the high-normal range. (The last serum Phe concentration is 12 mg/dL)


A 41-year-old gravida 4 para 2 patient at 15 weeks and 5 days of gestation (based on ultrasound) presented to an outside hospital with decreased appetite and severe vomiting. She had WHO class III obesity (BMI 45.1 kg/m2) but was otherwise healthy. Initial laboratory tests showed a white blood cell count (WBC) 14 k/µL, hemoglobin (Hgb) 13.7 g/dL, platelets (PLT) 354 k/µL, normal blood smear, aspartate aminotransferase (AST) 354 IU/L, alanine aminotransferase (ALT) 574 IU/L, alkaline phosphatase (ALP) 125 IU/L, and total bilirubin (TB) 4.8 mg/dL. Abdominal ultrasound and magnetic resonance cholangiopancreatography showed hepatic steatosis, pericholecystic fluid, and gallbladder wall thickening. Further workup revealed a positive anti-nuclear antibody (ANA) with 1 : 640 titer but was otherwise negative for infectious, metabolic, or serologic etiologies. She was treated with methylprednisolone and antibiotics (ceftriaxone and metronidazole) for presumed hyperemesis gravidarum and acalculous cholecystitis, respectively. By the fifth hospital day, she felt greatly improved and tolerated food by mouth; laboratory results showed AST 91 IU/L, ALT 185 IU/L, ALP 127 IU/L, and TB 7.3 mg/dL. She was discharged with a steroid taper and antiemetics.
Three days later, she presented with vomiting, pruritus, and jaundice despite medication adherence. Laboratory testing revealed WBC 18.4 k/µL, Hgb 12.1 g/dL, PLT 166 k/µL, AST 51 IU/L, ALT 88 IU/L, ALP 191 IU/L, TB 15 mg/dL, total protein 6.8 mg/dL, albumin 2.6 mg/dL, serum creatinine 1.0 mg/dL, and international normalized ratio (INR) 2.2 mg/dL. She was transferred to our facility due to her advanced age, history of preterm delivery, and hepatic decompensation. She was alert and oriented with stable vital signs on admission. Complete blood count and comprehensive metabolic panel showed comparable values to those at her outpatient visit. Human immunodeficiency virus, hepatitis B surface antigen, total core antibody, e antigen, and hepatitis C surface antibody testing were nonreactive. Extensive viral and bacterial testing was negative. She denied fever, sick contacts, or recent travel outside of the country. The patient was not taking acetaminophen, amiodarone, antiretrovirals, methotrexate, piroxicam, tetracycline, tolmetin, valproate, or other sources of drug-induced liver injury. Repeat ANA was positive with a >1 : 1280 titer; additional autoantibodies and anticardiolipin were negative.
The patient was admitted to the hospitalist service and various consultants assisted with care. An abdominal ultrasound showed hepatic steatosis and an incidental absent fetal heart rate later confirmed by fetal ultrasound on day 2. Dilation and evacuation were performed on day 3. By this point, the differential diagnosis included AFLP, hemolysis with elevated liver enzymes and low platelets (HELLP), intrahepatic cholestasis of pregnancy (IHCP), and autoimmune hepatitis (AIH). Lack of cholestasis on imaging (ultrasound and MRCP) was inconsistent with IHCP. Preeclampsia, HELLP, and AFLP were considered unlikely based on gestational age, absence of hypertension, appropriate platelet count, and normal peripheral smear. If due to AFLP, the presumption was that it should improve postpartum. However, laboratory work on day 4 showed a rising ALP 226 IU/L and TB 20.5 mg/dL. Due to her positive ANA, she was empirically treated with methylprednisolone out of concern for AIH.
Liver biopsy was performed on day 5, which yielded inadequate tissue, but was suggestive of AFLP based on microvesicular steatosis. Acute renal failure, thrombocytopenia, and disseminated intravascular coagulation (DIC) developed over days 4–7, and a repeat biopsy on day 7 revealed significant microsteatosis, macrosteatosis, ballooning hepatocytes, and a mild inflammatory infiltrate without plasma cells, interface hepatitis, rosettes, or fibrosis (Figures and ). Several hours postbiopsy, the patient became encephalopathic, rapidly decompensated, and was transferred to a liver transplant center with multisystem organ failure. She expired before further intervention.


The patient is a 58-year-old male with a past medical history of insulin-dependent type 2 diabetes mellitus, who presented to our emergency room with a complaint of groin pain. He reported this pain which began one month prior to presentation and has been progressively getting worse. The pain was localized to the left groin with radiation down the left leg. The patient initially thought his pain was due to sciatica because of which he did not seek medical treatment. He endorsed pain while at rest and particularly with movement of the left leg and walking. He denied any complaints of fevers, chills, chest pain, shortness of breath, abdominal pain, nausea, vomiting, diarrhea, flank pain, dysuria, or hematuria. He also denied any incontinence of urine or bladder.
Upon presentation to the ED, the patient’s vital signs were a blood pressure of 134/81 mmHg, heart rate of 75 beats/min, 98.2°F, and oxygen saturation of 99%. His physical examination was significant for sacral pain on palpation, back pain, and abnormal gait. His laboratory studies are shown in Table .
He was administered vancomycin and piperacillin-tazobactam and taken for a CT scan (Figure ) which revealed a possible prostatic abscess with extension to the ischiorectal fossa and right gluteal region. Two fluid collections were also identified in the anterior aspect of the left hip. An MRI was also performed (Figures -), which revealed multifocal perirectal abscesses with extension to the inferior ischiorectal fossae, right greater than left. Abscesses were also seen at the anterior aspect of the left hip indicative of septic arthritis. The patient was continued on broad-spectrum antibiotics and was referred to the orthopedic surgery and general surgery services for incision and drainage of the left hip joint and rectal abscesses respectively. Subsequent wound culture analysis returned positive for methicillin-sensitive Staphylococcus aureus (MSSA), for which the patient’s antibiotics were adjusted to nafcillin.