A 17-year-old female neutered domestic shorthair cat was presented with a 2 cm rectal prolapse. The owner reported that the cat had a normal appetite and had been passing smaller-than-usual amounts of faeces for several days. The cat was wormed monthly (Advocate; Bayer). Physical examination revealed a low body condition score (3/9) and hepatomegaly.
Haematology revealed a mild, non-regenerative anaemia (haematocrit 24.5%; reference interval [RI] 30.3–52.3%) and a mild, mature neutrophilia (16.21 × 109/l; RI 1.48–10.29 × 109/l). Multiple biochemical analyses revealed a mild increase in alanine aminotransferase activity (222 IU/l; RI 12–130 IU/l). All other parameters, including total thyroxine, were within the RIs. Urinalysis showed adequate renal-concentrating ability (urine specific gravity 1.050) and dipstick analysis was unremarkable.
Abdominal radiographs were unremarkable apart from the marked hepatomegaly. The rectal prolapse was manually reduced under general anaesthesia and an anal purse-string suture was placed. Supportive care included intravenous fluid therapy, metronidazole (10 mg/kg IV q12h), cefazolin (30 mg/kg IV q8h), buprenorphine (0.015 mg/kg IV q8h) and esomeprazole (1 mg/kg IV q24h).
The following day abdominal ultrasound confirmed marked hepatomegaly. The liver was lobulated with a complex heterogeneous echotexture and irregular margins (). There were multifocal, well-defined, ovoid-to-circular regions within the hepatic parenchyma that contained echogenic fluid, which demonstrated an atypical echogenic swirling pattern. The intrahepatic bile ducts were enlarged. The gall bladder contained anechoic fluid with irregular wall thickening. The common bile duct was markedly distended with anechoic fluid from the level of the cystic duct to the duodenal papilla, with no evidence of intraluminal obstruction. There was a concentric ring pattern in the transverse plane at the level of the ICCJ with wall thickening suggestive of a caecocolic intussusception ( and ). There was a small volume of anechoic free peritoneal fluid. Abdominal ultrasound was otherwise unremarkable.
Coagulation times were within the RIs (prothrombin time 18 s [RI 15–22 s] and activated partial thromboplastin time 92 s [RI 65–119 s]). Thoracic radiographs were unremarkable. Hepatic mass fine-needle aspirate cytology identified well-differentiated hepatocytes.
The following day the purse-string suture was removed and colonoscopy under general anaesthesia revealed an abrupt end at the entrance to the caecum. Multiple endoscopic colonic biopsies were collected. Exploratory laparotomy was then performed via a ventral midline approach. There was a single 7 cm × 7 cm × 4 cm mass with an irregular nodular contour replacing the quadrate lobe of the liver (). The remaining liver appeared enlarged with rounded margins and multiple scattered nodules. The common bile duct was markedly dilated. The quadrate lobe was resected using a 30 mm TA-stapler (TA autosuture; Covidien). The caecum was inverted into the colon and was unable to be reduced (). An antimesenteric colotomy was performed adjacent to the caecal inversion and extended to include the circumference of the inverted section. The colotomy was closed and a typhlectomy was performed. The base of the caecum was oversewn with 4-0 absorbable monofilament suture in a Parker-Kerr suture pattern to invert the edges. Abdominal wall closure was routine. Examination of the inverted caecum following resection revealed a distinct 1 cm × 1 cm focal, pedunculated mass arising from the mucosa and of the same colour as the mucosa. Postoperative analgesia was provided by a fentanyl continuous rate infusion (6 µg/kg/h for 24 h) followed by buprenorphine (0.015 mg/kg IV q8h for 48 h). The cat also received cefazolin (30 mg/kg IV q8h for 48 h) and amoxicillin–clavulanate (20 mg/kg PO q12h for 7 days) postoperatively.
Histopathology of the excised liver mass showed a proliferation of well-differentiated hepatocytes forming irregular plates of variable width, and lacking a defined lobular architecture or portal structures. Anisokaryosis was moderate with individual karyomegalic cells (diameter 2–3 times normal) having 1–2 large eosinophilic or basophilic nucleoli. Mitoses were present in low number (four per 10 high-powered × 40 fields). There was moderate multifocal cytoplasmic vacuolation (consistent with lipid and glycogen accumulation), and stromal tissue was inconspicuous. There was scattered individual cell death, multiple small necrotic foci, and acute and chronic haemorrhage (10% of the specimen). Tumour growth was nodular, although the margin with normal liver was irregular and infiltrative. Variably sized, sometimes blood-filled, cystic spaces were prominent and were lined by flattened endothelial cells (dilated vasculature and sinusoids) or by proliferating hepatocytes (in areas of necrosis). The changes were consistent with a well-differentiated hepatocellular carcinoma with a trabecular growth pattern and cystic foci ().
Histopathology of the excised caecum included a pedunculated intraluminal polypoid mucosal projection with a submucosal stalk. Overlying mucosal epithelial cells were mildly hypertrophied, but significant dysplasia was not a feature. The regional mucosal-associated lymphoid tissue was reactive (enlarged, coalescing follicles, enlarged germinal centres), and of increased density in the polyp. The mucosa of the polyp and adjacent caecum contained a moderate plasmacytic infiltrate, with fewer lymphocytes and occasional neutrophils. There was mild multifocal mucinous gland dilatation. A focus of caecal mucosal ulceration showed more intense inflammation and a neutrophilic serocellular crust. Adjacent tunica muscularis was attenuated, and overlying oedematous serosa expanded by a mild mononuclear inflammatory infiltrate, lymphoid aggregates, ectatic lymphatics and early fibroplasia. The changes were consistent with a hyperplastic inflammatory polyp, moderate chronic typhlitis and regional caecal wall degenerative changes with early repair (). Histopathology of the colonic mucosal biopsies showed comparatively minor mucosal inflammation only.
The cat recovered well after surgery and was discharged 3 days later. Reassessment 6 weeks later revealed a 0.5 kg weight gain, a body condition score of 5/9 and resolution of clinical signs. Revisits every 3 months were recommended but not kept by the cat’s owner. The cat died acutely 1 year later. The cause of death was not determined and necropsy was not performed. The owner reported that the cat had been well prior to its death.


The 29-year-old male patient had been followed-up for schizophrenia for about 5 years. He had several symptoms including introversion, impaired social functioning, and unwillingness. He had used olanzapine and risperidone at standard doses and for an adequate period of time. In the process, auditory hallucinations and suicidal thoughts had occurred, and he had been hospitalized twice.
He was admitted to our department with positive symptoms two years ago. On the first hospital day, common blood cell count, routine biochemical tests, electrocardiogram and EEG were done. All test results were within normal limits. Clozapine (25 mg/day) was started and showed inadequate response. Low dose titration up to 200 mg/day was done within 4 weeks. Remission was achieved with 200 mg/day clozapine.
At the third month of treatment, he had a tonic-clonic seizure witnessed by his mother. It lasted 30–40 seconds with a loss of consciousness, deadlock in the chin and urinary incontinence. The patient was in a state of confusion when he arrived the emergency room of our hospital. He had no epileptic seizures before and there was no history of epilepsy in first-degree relatives. There was no history of alcohol use, drug use or head trauma. His body weight was 71 kg, waist circumference was 84 and body mass index was 23.2 kg/m2. Blood biochemistry test results (fasting blood glucose levels of serum electrolytes, and renal and liver function tests) were normal. Bilateral diffuse epileptic activity was detected at EEG (). The results of the investigations that were performed to rule out other causes of seizures (brain computerized tomography scan, brain magnetic resonance imaging) were normal. The seizure was considered to be triggered by clozapine, according to neurological consultation. Clozapine was reduced to 100 mg/day, and valproic acid 1,000 mg/day was started. EEG performed at 2 weeks, and 4 months after the seizures showed no abnormality (). There was no change in the patient’s weight. Seizures did not recur in the patient’s follow-up and psychotic symptoms were under control. The patient has taken the same treatment until now and is in remission.


A 34-year-old man with no asbestos or cigarette exposure was admitted to our ward due to worsening cough and exertional dyspnea for 10 years. He had continually been healthy before 2003. The patient had a “flattened thoracic cage” and bibasilar inspiratory crackles without finger clubbing. A series of chest computed tomography scans during the preceding 10 years revealed the presence of gradual, exaggerated, upper lung-predominant, diffuse pleural thickening, and dense subpleural opacification with traction bronchiectasis (Fig. A–D). Assessments of antinuclear antibody, antiextractable nuclear antigen, antineutrophil cytoplasmic antibodies, human leukocyte antigen-B27, and rheumatoid factor all produced negative results. A pulmonary function test in November 2013 revealed restrictive ventilatory dysfunction and impaired diffusion, with the following specific findings: forced vital capacity (FVC), 1.3 L/41.2% of predicted; the ratio of forced expiratory volume in 1 second (FEV1) to FVC (FEV1/FVC), 84.7%; total lung capacity (TLC), 2.31 L/33.1% of predicted; and diffusion capacity of carbon monoxide (DLco), 4.12 mmol/min/kPa/36.5% of predicted. In December 2013, a video-assisted thoracic surgical (VATS) lung biopsy revealed thickened visceral pleura and prominent subpleural fibroelastosis (Fig. A, B), confirming the diagnosis of iPPFE. Prednisone at an initial dosage of 1 mg/kg/d and cyclophosphamide (2 mg/kg/d) were prescribed beginning in January 2014. Prednisone was tapered after 2 weeks. Because the patient's clinical condition had not improved after 8 months of treatment, prednisone and cyclophosphamide were discontinued. Subsequently, the patient was consulted regarding lung transplantation and was placed on a transplantation list. He was administered 1800 mg/d pirfenidone for approximately 6 months starting in February 2015. However, his respiratory condition gradually deteriorated, and his pulse oxygenation at rest was less than 90%. In May 2016, bilateral lung transplantation was successfully performed. After the patient recovered from transplantation, he did not require supplemental oxygenation. PPFE was pathologically confirmed based on his extracted lung.


A 71-year-old man was transferred to the emergency room because of a persistent fever. One month previously, he had visited a different hospital for the same reason and was administered antituberculous therapy because of suspected pulmonary tuberculosis as indicated on a chest computed tomography (CT) scan. Right after taking this medication, thrombocytopenia (57,000 cells/mm3), anemia (10 g/dL), and gastrointestinal discomfort developed, and medication was stopped. Three weeks later, he regained his fever and experienced nausea and vomiting. Treatment with broad-spectrum antibiotics was ineffective. At the time of emergency room admission, his major symptoms were a fever up to 40°C and chills. The physical examination findings were normal, except for pretibial pitting edema (++/++) in both legs. The spleen was not palpable and not enlarged on abdominal CT (Fig. A). Cultures of blood, urine, and sputum were subjected to tests for influenza virus, urinary streptococcus pneumonia antigen, Hantaan virus, Tsutsugamushi orientalis, the human immunodeficiency virus, malaria, and the presence of antinuclear antibodies; all of the results were negative. Ferritin was 98 ng/mL and fibrinogen was 257 mg/dL. The initial blood chemistry tests showed a total bilirubin level of 0.67 mg/dL, aspartate aminotransferase (AST) of 35 IU/L, alanine aminotransferase (ALT) of 14 IU/L, alkaline phosphatase (ALP) of 252 IU/L, and lactate dehydrogenase (LDH) of 894 IU/L. Peripheral blood smears repeatedly revealed leukopenia with neutropenia and thrombocytopenia without clinical significance. Bone marrow examination revealed near-normal trilineage hematopoiesis, except for iron deficiency anemia.
Approximately 2 to 3 weeks later, blood chemistry results were elevated, with a total bilirubin of 1.68 mg/dL, AST of 48 IU/L, ALT of 43 IU/L, ALP of 1331 IU/L, gamma-glutamyltransferase of 235 IU/L, and LDH of 1616 IU/L. These results led us to suspect an infiltrative liver disease; therefore, the abdominal CT was repeated and revealed hepatosplenomegaly, which was not observed initially (Fig. B). Also, his thrombocytopenia and anemia (8 g/dL) had worsened and his ferritin was elevated up to 1585 ng/mL. Hemaphagocytic lymphohistiocytosis was suspected based on these findings, but soluble CD25 and NK cell activity were not able to be measured at out hospital, which was the only available laboratory in Korea.
A liver biopsy was necessary to confirm a diagnosis, but the traditional percutaneous liver biopsy approach was not performed because severe thrombocytopenia (15,000 cells/mm3), which was unresponsive to repeated transfusions and, increased the risk of bleeding complications. Instead, we performed a transjugular liver biopsy with fluoroscopic guidance. This alternative approach accessed the liver parenchyma through the superior vena cava and hepatic vein to obtain hepatic tissue without liver capsule breaks (Fig. ).
The liver biopsy specimen revealed infiltration of large lymphoma cells with irregular shaped nuclei in the sinusoidal, portal, and central venous regions.[ Lymphoma cells were positive for anti-CD20 antibody, but negative for CD3 and CD5 (Figs. C and D).[ All findings were consistent with IVLBCL. Unfortunately, the patient died because of the progression of the disease before treatment could be administered.


A A 44-year-old woman with chronic lymphedema in her left lower limb for nearly
20 years caused by Cockett´s syndrome, an anatomical variation in wich the left
iliac artery compresses the left iliac vein, was admitted to the dermatology
service due to the development, over the preceeding four months, of a painful
red-topurple macule on the affected limb. It rapidly progressed to purple
extensive macules, papules and nodules lesions, some of them with a tumoral
aspect. ().
Incisional biopsies of the lesions were performed. Histopathological exams
revealed, in the purple macule lesion, proliferation of irregular vascular
clefts, interposed by the dermal collagen fibers, formed by endothelium with
atypical nuclei, prominent toward the lumen; The tumoral lesion exhibited
cohesive epithelioid masses of atypical, large, rounded cells with acidophilic
cytoplasm and frequent mitotic figures. (). Immunohistochemical analysis was negative for HHV-8 Lana-1
oncoprotein and revealed expression of CD31 and CD34.
Based on these results, it was diagnosed as epitheliod AS and, therefore,
Stewart-Treves syndrome, due to the association with chronic lymphedema.


An 80-year-old of black color man, with a poorly defined disease onset - three to
eight months before admission - reported an initial reddish purple lesion on the
scalp that developed into extensive, infiltrative, confluent purple-black
lesions spreading from the scalp to the lower third of the face, forming an
easily bleeding left periorbital mass (, with consent).
Anatomopathological study of the skin biopsy demonstrated proliferation of
irregular vascular clefts, consisting of atypical endothelium, with
hyperchromatic nuclei projecting into the lumen, leading to the diagnosis of AS
().


A 57-year-old woman developed, over the previous three years, papulotumoral,
red-to-purple, hardened, asymptomatic lesions, located on the lower lateral
quadrant of the left breast. ().
She had a personal history of infiltrating ductal carcinoma in the affected
breast, diagnosed in 2008, and had undergone six cycles of neoadjuvant
chemotherapy, with complete clinical, radiological and pathological responses.
In 2009, conservative surgery of the left breast (superior quadrantectomies) was
performed with axillary emptying, followed by 30 sessions of radiotherapy.
Histopathological examination of the surgical specimen showed no residual
neoplasia with negative lymph nodes.
Histopathological examination of a breast papule demosntrated anastomotic suture
of sinusoidal vessels, with an infiltrative aspect, coated by mild to moderately
atypical endothelium, whose nuclei projected into the vessel, consistent with a
diagnosis of lowgrade AS. ().


We report a 39-year-old dark-skinned female patient from Natal (RN) presented with
diarrhea with small amount of mucous and bloody discharge 8 months previously (5
episodes/day). The symptoms were accompanied by diffuse abdominal pain, weight loss,
fever and generalized arthralgia. Concomitantly, we observed infiltrated nonpruritic
round erythematous-violaceous plaques, some with mammillated surface, measuring
0.5-2.0cm in diameter. The lesions were distributed on the upper trunk, back, upper
limbs and palms. The patient sought dermatological care and a specimen of the lesion
on the right arm was sent to biopsy (
to ).
Histopathological analysis revealed orthokeratosis with parakeratosis foci. The
dermis showed vascular ectasia, edema, and interstitial and perivascular mononuclear
infiltrate consisting of lymphocytes and histiocytes, characteristics features of
histiocytoid SS (). Initial treatment
consisted of oral prednisone (40mg/daily) and clobetasol topical. Although lesions
resolved completely, the patient kept the initial gastrointestinal complaints.
Laboratory tests revealed anemia without leukocytosis, iron deficiency, ESR 87 mm/h,
CRP 13.9mg/dL, and nonreactive ANA test. Serology for HIV and syphilis, as well as
stool and blood cultures, were negative. Colonoscopy with biopsy showed colon with
loss of vascular pattern, edema, enanthem, nodules, and longitudinal ulcerations
covered by fibrin with cryptitis outbreaks, and crypt abscess. Histopathological
examination revealed moderate lymphocytic polymorphonuclear infiltration,
corroborating the diagnosis of active pancolonic CD ().
The patient was referred to the gastroenterology service and was treated with
mesalazine 1200mg/daily continuing with the oral corticosteroid therapy with good
clinical response. After 12 months of follow-up, intestinal symptoms remained stable
and skin lesions showed no recurrence.


A 16-year-old female patient was admitted to Uijeongbu St. Mary's Hospital for the management of refractory colonic CD (A1L2B1 Montreal classification for Crohn's disease 2005). CD was diagnosed 1 year prior, according to standard endoscopic and histologic criteria (). CD was remitted with prednisone, and maintenance therapy with mesalazine and 6-mercaptoprine was administered. Four months prior to hospital admission, she was treated with infliximab (5 mg/kg) because of several flares, and she responded well; however, colitis aggravated 1 month before admission. On admission, the patient's body temperature was 37.1℃, and she had poor general condition. Laboratory examination showed the following: leukocyte count, 8,260/mm3 with 51.7% neutrophils; hemoglobin, 8.1 g/dL; ESR, 36 mm/h; CRP level, 6.17 mg/dL; and serum albumin level, 3.0 g/dL. A stool specimen contained white blood cells, and a test for Clostridium difficile toxin was negative. Immunohistochemical staining for cytomegalovirus was negative. Even after the infliximab dose was increased to 10 mg/kg, repeat colonoscopy showed active colitis (), and the patient became steroid dependent.
Her CDAI score was 394; thus, treatment with FMT was discussed with the patient and her parents, and they agreed to treatment. The FMT procedure was performed on day 12 after hospital admission. The FMT stool source, a family donor, received both blood and stool tests, and HBsAg, anti-HCV, Veneral Disease Research Laboratory test, C. difficile toxin, and human immunodeficiency virus were not detected. The donor had no history of antibiotic use within the past year or any history of chemotherapy. Sixty grams of stool was mixed in 250 mL of normal saline and homogenized using a mechanical blender. The suspension was filtered through gauze to remove larger particulate matters. FMT was performed using gastroduodenoscopy; the endoscope was inserted into the second portion of the duodenum, and the prepared fecal suspension was transferred to the patient's bowels through the biopsy channel of the endoscope. The procedure time was approximately 5 minutes. One day after FMT, the patient developed abdominal pain and a transient fever; however, these symptoms disappeared after conservative care. One week after FMT, the patient felt well and had 1 to 2 formed bowel movements per day with no abdominal pain. The CDAI was reduced to 132, and the patient was discharged. Although clinical remission was achieved, the patient wished to receive maintenance treatment. After FMT, mesalazine (3.0 g/day) and azathioprine (50 mg/day) was administered for maintenance therapy. In addition, 2 months after FMT, she was administered infliximab (5 mg/kg) intravenously, to which she responded well, and treatment with infliximab was continued every 2 months. A follow-up colonoscopy 10 months after FMT showed improvement in the mucosal lesions (). Clinical remission was sustained for more than 12 months, and the follow-up is ongoing ().


A 42-year-old male presented to the medical emergency department with complaints of weakness and significant weight loss over 1 year. He had episodes of low-grade fever in the past year, for which the patient was treated for pulmonary tuberculosis 2 years back. At present, he was again put on antitubercular therapy (ATT) for the past 1 month; however, no improvement was noted and hence the patient was referred to our hospital. There was no significant family history. On general physical examination, the patient was found to be thin built, pale, and afebrile with abdominal distension. Left submandibular and left axillary lymph nodes were enlarged and measured 1.5 cm in diameter. Mild hepatosplenomegaly was noted, however no fluid thrill could be discerned. Ultrasound abdomen revealed enlarged multiple conglomerate of mesenteric lymph nodes with the largest node measuring 22 mm × 18 mm. Clinical chemistry revealed A:G reversal with total protein of 9.5 g%, albumin of 2.0 g%, globulin of 7.5 g%, and A:G ratio of 1:3.75. Other parameters of liver function test and kidney function test were found to be within normal limits. Complete hemogram revealed pancytopenia with hemoglobin: 6 g%, total leukocyte count: 1800/μL, differential leukocyte count: polymorphs 47%, lymphocytes 51%, eosinophils 1%, monocytes 1%, platelets: 48,000/μL, and erythrocyte sedimentation rate (ESR) of 50 mm/h. Peripheral smear revealed the presence of rouleaux; however, no hemoparasite was noted.
Fine needle aspiration cytology was performed on the left submandibular and axillary lymph nodes, which yielded thick aspirate. Smears prepared showed few epithelioid cell granulomas interspersed with discrete and aggregates of histiocytes in a background of reactive lymphoid cells and many plasma cells. Numerous intracellular as well as extracellular amastigote forms of Leishmania species were seen []. In view of strong clinical suspicion, Ziehl–Neelsen staining for acid-fast bacilli (AFB) was also done which came out to be negative. Both polymerase chain reaction for Mycobacterium tuberculosis and AFB culture yielded negative result. Later on, rK39 antigen was also found to be positive. Bone marrow examination (both aspirate and biopsy) revealed a prominence of plasma cells and histiocytes along with infiltration by numerous intracellular as well as extracellular amastigote forms of Leishmania spp. Average parasite density (APD) of 5+, i.e., 10–100 Leishman–Donovan (LD) bodies/field, was noted in the bone marrow aspirate (BMA) []. In view of high APD, the patient's human immunodeficiency virus (HIV) status was evaluated which showed positive serology. Immune status evaluation revealed a low CD4 count; 28/μL (reference range: 400–1600/μL). The patient was started on intravenous amphotericin B along with highly active antiretroviral therapy. Improvement was noted after 14 days of treatment (CD4 count: 36/μL). Subsequent bone marrow evaluations revealed a significant fall in APD and clinical improvement in patient's health; weight gain, improved appetite, and rise in CD4 counts.


A 1-month-old boy was referred to our hospital due to severe and progressively worsening cyanosis and tachypnea. He weighed 3.3 kg. On examination, he was saturating 58% and had severe respiratory distress. The child was intubated and put on ventilator. Echocardiogram showed Tetralogy of Fallot (TOF) with severe infundibular stenosis. Right and left pulmonary arteries were 4.8 mm and 3.3 mm, respectively. Nakata index was 131. Pulmonary artery valve annulus was rather large 5.6 mm (z-score - 2.1), but the infundibular area was 2.2 mm. Patent ductus arteriosus (PDA) was almost closing despite prostaglandin E1 infusion. The patient was brought to the catheterization laboratory as an emergency case for the PDA or right ventricular outflow tract (RVOT) stenting. Descending aortogram was done using 4F pigtail catheter, and PDA anatomy was profiled. The ductus came from underneath transverse aortic arch with tight curve and constricted at the pulmonary artery side []. We decided to proceed the RVOT stenting at first. Right ventricular angiogram was done using 5F Judkins right (JR) catheter. Outflow tract was severely thickened with the prominent muscle bundle at end systole, and valve was doming. 5F Launcher guiding JR catheter was positioned at the lower part of outflow tract, and Hi-torque Balance Middleweight Elite guidewire 0.014 inch (Abbott Laboratories, Abbott Park, Illinois, USA) was advanced distally in the right pulmonary artery. After removing 4F Judkins catheter, Accuforce coronary balloon (Terumo Interventional Systems, Somerset, New Jersey, USA) 5 mm × 12 mm was placed across the pulmonary valve and dilated at its maximum pressure. A waist of the balloon was not observed. Oxygen saturation did not improve at all. Then, Azule coronary stent (OrbusNeich, Wanchai, Hong Kong) 3.5 mm × 12 mm was deployed across the RVOT just below the pulmonary valve to open the RVOT and preserve the pulmonary valve at the same time. Nevertheless, the stent migrated downward as the balloon was deflated and wire removed []. The child developed complete heart block, and a temporary pacing wire was inserted to the right ventricle and pacing started. We decided to convert to the PDA stenting. Right axillary artery access was taken with 4F sheath. Judkins catheter 4F was positioned at the mouth of duct artery, and hand angiogram of the PDA delineated the anatomy of PDA and arborization branch pulmonary arteries. We decided to balloon dilate the PDA at first. Runthrough guide-wire (Terumo Interventional Systems, Somerset, New Jersey, USA) 0.014 inch was positioned distally in the left pulmonary artery. A 2.5 mm × 15 mm Tazuna percutaneous transluminal coronary angioplasty balloon (Terumo Interventional Systems, Somerset, New Jersey, USA) was set across the PDA and dilated to its maximum caliber. Choice PT Floppy Guide Wire (Boston scientific, Marlborough, Massachusetts, USA) was positioned beside the first wire in the left pulmonary artery as a support. The first Runthrough wire was repositioned in the right pulmonary artery, and Accuforce coronary balloon 3.5 mm × 12 mm was set across the PDA and dilated after removing the second wire. Integrity coronary stent (Medtronic CardioVascular, Santa Rosa, California, USA) 3.5 mm × 18 mm positioning to the PDA followed this. Multiple hand injections at the PDA were done to make sure the stent position, and finally, the stent was deployed. After PDA stenting, oxygen saturation increased from 58% to 84%. The postprocedure descending aortogram revealed good stent position, entirely covering PDA []. Postprocedure echocardiography showed the migrated stent hung at the tricuspid valve and ventricular septal defect but did not cause valve insufficiency. Complete atrioventricular block improved 1 day after the procedure, and the temporary pacemaker was discontinued. The child was extubated on the 4th day and transferred to the step-down unit ward on the 6th day. Six months later, the patient was referred to the TOF repair. Computed tomography before surgery showed well-developed pulmonary arteries. Right and left pulmonary artery sizes were 6.4 mm and 5.6 mm, respectively, and Nakata index increased to 200. At the surgery, PDA stent was divided and removed. The migrated stent was located in the trabecular portion below the aortic valve. The stent was retrieved completely. There were no adhesions on its surface. Pulmonary valve and branch pulmonary artery sizes were good. TOF repair was completed without using transannular patch.


Case 1 was an 8-month-old castrated male domestic shorthair cat presented to the veterinary referral hospital with a 2 week history of progressive paraparesis and constipation. The owner also reported progressively worsening urinary incontinence when the cat was adopted at 3 months of age. A physical examination revealed a palpable dermoid fistula over the caudal vertebra. A neurological examination showed proprioceptive deficits in the hindlimbs and the absence of anal and perineal reflexes. The lesion was neuroanatomically localised to the L4–S3 spinal cord segments. A complete blood count and biochemistry panels were within normal limits. MRI (EXCELART Vantage 1.5 Tesla; Toshiba) and CT (Aquilion 64-slice scanner; Toshiba) were performed. The palpable dermoid fistula was hyperintense on T2-weighted images (T2WI) and hypointense on T1-weighted images (T1WI), and was connected to the dural sac on the conus medullaris. This fistula appeared to have retracted the spinal cord caudally (). CT images revealed the lack of the dorsal arches of S3, Cd1 and Cd2 vertebrae and ventral displacement of the caudal vertebra (). Severe fecal impaction was also present. Based on these imaging findings and clinical signs, caudally retracted TCS secondary to SBA was suspected.
The excision of caudal SBA and caudectomy were performed under general anesthesia to release the tethering of the spinal cord and resolve rectal narrowing secondary to ventral displacement of the caudal vertebra. After premedication with intravenous atropine (Atropine; Tanabe) (0.05 mg/kg) and midazolam (Midazolam; Astellas) (0.2 mg/kg), general anaesthesia was induced with propofol (Propoflo 28; DS Pharma Animal Heath) (5 mg/kg, to effect IV) and maintained with isoflurane in oxygen. Fentanyl (Fentanyl; Daiichi Sankyo) (loading dose of 5 µg/kg IV followed by continuous rate infusion at 5–10 µg/kg/h IV) was administered as intraoperative analgesia. Dorsal lumbosacral laminectomy from L7 to S3 was then performed. When the vertebral canal was opened, the fistula communicating with the dural sac on the conus medullaris was observed. After the incision of the meninges, the fistula caused caudodorsal displacement and traction of the conus medullaris (). The fistula was completely removed, and the spinal cord was untethered. Dura regeneration matrix (expanded polytetrafluoroethylene [ePTFE] soft tissue patch; GORE-TEX) was placed over the defect of the dura prior to standard closure. The vertebra caudal to S3 was resected in order to release rectal narrowing secondary to ventral displacement. The cat was discharged on the eighth postoperative day.
A 1 month postoperative examination showed improvements in paraparesis and constipation symptoms. A follow-up MRI revealed the release of the conus medullaris tethering and an improvement in rectal narrowing (). Urinary incontinence remained partially unresolved. The histopathological examination showed that the resected fistula was consistent with a segment of the spinal cord parenchyma that contained remnants of the central canal lined by cuboidal-to-columnar cells, resembling ependymal cells. This parenchyma was surrounded by a thin layer of fibrous tissue resembling the meninges. Multiple small capillaries, glial cells and occasional neurons were observed within the spinal cord parenchyma. Based on these findings, the lesion was diagnosed as a meningomyelocele ().


Case 2 was a 10-month-old castrated male domestic shorthair cat referred to the veterinary referral hospital for a 6 month history of progressive paraparesis and an over-reaching pelvic limb gait. A physical examination revealed a palpable dermoid fistula at the level of T5. A neurological examination showed proprioceptive deficits and upper motor neuron signs in the hindlimbs, which suggested a T3–L3 spinal cord lesion. The palpable dermoid fistula showed hypointensity on T2WI and T1WI, and was detected as a tubular structure connected to the dural sac on the thoracic spinal cord. The tubular structure caused dorsal traction of the spinal cord. CT revealed a dorsal lamina defect between the spinous processes of T5 and T6 (,). Dorsally retracted TCS secondary to SBA was suspected.
The excision of SBA was performed to untether the spinal cord under general anaesthesia. The same perioperative analgesics as case 1 were administered. The cat was positioned in sternal recumbency and standard dorsal laminectomy of T5 and T6 were performed. The tubular structure connected to the dural sac was observed (). After the incision of the meninges, the tubular structure was completely removed and the spinal cord was untethered. The meninges were then sutured (CV-6 ePTFE Suture; GORE-TEX). A postoperative MRI examination confirmed the removal of the tubular structure and untethering of the spinal cord (). The cat was discharged 7 days postoperatively.
In 1 week and 1 month follow-up neurological examinations the cat showed continuous improvements; however, the over-reaching pelvic limb gait persisted. In the 12 month follow-up, other than pelvic limb ataxia, the cat was able to jump and run freely. Histologically, the tubular structure revealed spindle cells arranged in interlacing fascicles (meningeal-like cells) surrounded by well-differentiated collagen fibres. Immunohistochemically, these meningeal-like cells were positive for E-cadherin. The tubular structure did not contain any neurons and/or glial cells. This confirmed the diagnosis of a meningocele ().


A 10-year-old girl presented with a 2-week history of a continuous
headache, which was aggravated by accompanying nausea. Brain computed tomography showed acute hemorrhage in the region of the right lateral ventricle and obstructing hydrocephalus (). Brain magnetic resonance image revealed an approximately 3.6-cm, well-defined mass on the body of the right lateral ventricle. The mass showed mixed low and high signal intensity on T1-weighted () and T2-weighted images (). Following gadolinium administration, a heterogeneous enhancement was observed for the peripheral solid areas (). The cerebral blood volume was focally increased in the MR-enhanced areas (). The mass was a well-defined, heterogeneously enhanced lesion with mixed cystic and solid components. It contained multistage hemorrhages in the right-sided foramen of Monro. The radiological differential diagnoses included high-grade glioma, SEGA, and choroid plexus tumor. The tumor was completely resected via a transcallosal approach. Intraoperatively, the mass presented as a gray-colored, firm tumor associated with acute and subacute hemorrhages. The origin of the mass was the ventricular septum adjacent to the foramen of Monro. A pathological analysis revealed pleomorphic multinucleated eosinophilic tumor cells with abundant cytoplasm, associated with increased vascularity (). The tumor cells showed focal positive staining for the glial fibrillary acidic protein () and strong positive staining for the S100 protein (). The Ki-67 labeling index was less than 1%. A diagnosis of SEGA was established. The patient recovered without any neurological symptoms. On an evaluation of TSC, there is no family history of TSC and there were no cutaneous stigmata of tuberous sclerosis. A clinical evaluation was performed including echocardiography, renal ultrasonography, ophthalmologic examination, and skeletal imaging. No features of TSC were observed. A genetic study was not performed. The radiological follow-up showed no recurrence for 2 years ().


A very active 10-year old male presented with a 2-week history of daily headaches. His background included asthma, atopy, and a proven allergy to cat hair. He was born full-term with no puerperal complications. Immunizations are up to date and he had achieved developmental milestones.
He described the headaches as pressure-like bilaterally, worse mid-morning, and again in the evening. There were no obvious triggers and he did not experience aura. The headaches did not wake him in the night and there was no associated vision or speech change. He began to have associated vomiting and an optician noted bilateral papilledema with splinter hemorrhages resulting in urgent referral to the local hospital.
On examination, there were no dysmorphic features or neurocutaneous stigmata. Head circumference was above the 99th centile for his age. Fundoscopy confirmed bilateral papilledema with splinter hemorrhages. Full neurological, cardiovascular, respiratory, and abdominal examination were otherwise unremarkable.
Computer tomography (CT) of the brain revealed panventriculomegaly and crowding at the craniocervical junction secondary to cerebellar tonsillar descent. Magnetic resonance imaging (MRI) of the neural axis excluded space-occupying lesions, venous sinus thrombosis, or spinal cord pathology. Dilated ventricles were seen with no evidence of transependymal edema. Intracranial pressure (ICP) monitoring confirmed pathological ICP (multiple B waves and mean ICP of 22 mmHg in a 24 h period). A right parietal ventriculoperitoneal (VP) shunt was inserted with a Codman-Hakim medium-low pressure valve. No immediate complications were encountered.
In the following days, the patient developed persistent low-pressure headache. This progressed to unresponsive episodes with rapid alternating eye movements associated with significant desaturations that were short-lived. CT scan of the brain showed smaller ventricular size and no change to the craniocervical junction. Following this, there was an episode of transient loss of vision followed by diplopia although detailed clinical examination of the eyes was normal including fundoscopy on this occasion. It was noted that the patient was tending to be hypertensive.
A repeat MRI scan of the brain shown in revealed a decompressed right lateral ventricle. There were new signal changes in the occipital lobes and cerebellar hemispheres. The diagnosis of posterior reversible encephalopathy syndrome (PRES) was made on clinical and radiological grounds. The patient was started on dexamethasone since the high pressures in the posterior fossa were thought to contribute.
Soon after, a quick recovery was observed with return to normal vision, no focal neurology, and well enough for discharge home. A CT scan just before discharge showed improved sulcal pattern with resolution of the cerebellar tonsil descent. At 3-month follow-up, the patient remains neurologically stable with a functioning VP shunt.


A 1-year-old second born male child, born to a third-degree consanguineously married couple with uneventful perinatal history, was brought with regression of milestones and seizures. The onset of clinical symptoms began at the age of 6 months with gradual loss of the milestones. The child had achieved response to sounds by 2 months; head holding, social smile, and recognition of mother by 3 months of age. Initially, he lost social smile and recognition of mother followed by control of neck. He lost all the milestones by 8–9 months of age. The child developed exacerbated startle response since 8 months of age and multiple episodes of right-sided focal seizures from 11 months of age. There was a history of sibling death at the age of 18 months with similar complaints.
On examination, head circumference was 44 cm (between 3rd and 15th centile) with coarse facies. The tone was increased in all the limbs with power of 3/5 (Medical Research Council grade). Deep tendon reflexes were exaggerated with extensor plantar response. Fundus examination showed cherry-red spot in the macula, and there was no hepatosplenomegaly. Magnetic resonance imaging (MRI) shows hyperintensity of the basal ganglia (long white arrow) and hypointensity of the ventral thalami (open arrow) on T2-weighted sequences []. Based on above findings suspected to be a case of Sandhoff disease, the enzyme assay in leukocytes for β hexosaminidase total (A + B) revealed 61 nmhol/h/mg (normal, 905–2878). Gene testing was positive for homogenous missense substitution p. Cys534Tyr, c1601G>A, chr5:74016560G>A in exon 13 of HEXB gene.


We report a case of a 50-year-old Chinese female, right-hand dominant, manual labourer, who presented with multiple digit triggering. In September 2006, she had undergone steroid injection to left middle, ring fingers, right index and middle fingers with initial symptom relief. Subsequently, she had left middle, ring finger, right index, middle and ring finger trigger releases done during the period from May 2007 to October 2008 in four separate operations. She was discharged from further follow-up as all triggering resolved after surgery.
She came back to our clinic seven years later in November 2015 with recurrent triggering of right middle and ring fingers. This was associated with numbness of the radial three and half digits of right hand. On examination, there was median nerve neuropathy with decreased radial three and half digits sensation. Tinel’s and Phalen’s signs were both negative. There was tendon triggering with palpable clicking over the mid-palm during finger flexion. There was no evident triggering at the level of A1 pulley in all digits of right hand. Previous trigger release scars over the right middle and ring fingers were well healed with no underlying adhesions. There was no wrist tenderness and active range of motion in the wrist was full with no clicking.
Wrist ultrasound showed that the median nerve was swollen at the level of distal radius and was compressed at the level of the distal carpal tunnel. Cross-sectional area (CSA) at pisiform level was 11.6 mm2 (upper limit 11mm2). Flattening ratio (FR) and volar bulging (VB) of the flexor retinaculum were within normal ranges. The maximal thickness of flexor retinaculum was 1.7 mm. There was no evidence of anomalous masses or migration of the lumbricals into the carpal tunnel during finger flexion. At about the level of the mid-palm, there were linear calcifications related to the middle and ring finger tendon sheath (). The affected flexor tendons appear to become distorted as they glide past the areas of calcification. Tendons were round and smooth at A1 pulley level (). These calcifications were not evident on plain X-ray (), which was normal with no significant degenerative changes seen in carpal joints. The nerve conduction study showed severe right carpal tunnel syndrome with significant impaired conduction velocity (26.9 m/s). Laboratory tests including C-reactive protein, uric acid and rheumatoid factor were all normal.
She subsequently underwent surgery of right carpal tunnel release. Intraoperative findings showed thickened transverse carpal ligament and tight carpal tunnel. No extra lumbricals or mass lesions were seen on visible tendons throughout their excursions within the carpal tunnel (). There were some calcific plaques seen on the tendon sheath. Tendons were otherwise healthy. (). The previous palpated triggering at mid-palm immediately resolved and tendon excursion was normal after release of the carpal tunnel and no further exploration of the tendon sheaths was performed. On follow-up visit in our clinic, there was no more finger triggering or numbness.


A 6-month-old female Pomeranian presented (body weight = 1.0 kg) with tetraplegia for 3
days and was referred to the Animal Medical Centre of Yamaguchi University. The
neurological examination showed loss of proprioception and upper motor neuron paresis of
fore- and hindlimbs. Lateral radiography of the cervical region revealed ventral
subluxation of C2. Ventrodorsal radiography showed a deficit of the dens at C2. Stress
radiography of the cervical region with ventral flexion revealed that the distance
between the caudal margin of dorsal arch of C1 and the cranial margin of spinal process
of C2 was 3.7 mm () (normal range <4
mm). Sagittal MRI of the cranial cervical spine revealed severe compression of the
spinal cord at C1 to C2 level and indentation of the caudal cerebellum (). Sagittal computed tomography (CT) revealed an
occipital bony defect, and the cranial-most aspect of the dorsal arch of C1 was inserted
into the intracranial region from the foramen magnum ().
According to these examinations, the patient was diagnosed as AAS complicated by AOO,
CLM, and syringomyelia. The operative approach was divided into two phases. First, in
order to treat AOO, CLM and syringomyelia, foramen magnum decompression (FMD) and dorsal
laminectomy of C1 were planned to decompress the cerebellum and spinal cord. Then, in
order to stabilize the atlantoaxial joint, ventral fixation of the joint was planned for
the second phase. The first phase of surgery (FMD and dorsal laminectomy of C1) was
performed on the 7th day after the first consultation. Anaesthesia was induced with
propofol IV (7 mg kg-1 propofol; Intervet, Tokyo, Japan). An endotracheal
tube was inserted and isoflurane (Isoflu; DS Pharma Animal Health Co, Osaka, Japan)
anaesthesia was maintained at 1-2% using a low-flow, semi-closed circuit.
Analgesia was performed by preoperative intara muscular administration of ketamine
hydrochloride (5 mg kg-5 Ketalar; Daiichi Sankyo, Tokyo, Japan) and bolus
administration of fentanyl (Fentanyl; Daiichi Sankyo, Tokyo, Japan). In addition,
continuous rate infusion of fentanyl citrate (5 to 30 µg/kg/min) was used for
intra-operative analgesia.
The patient was positioned in sternal recumbency with the neck ventroflexed. A dorsal
midline incision was made extending from external occipital protuberance cranially to
the second cervical vertebra caudally. The superficial dorsal cervical musculature was
separated at the median raphe, exposing the underlying paired biventer cervicis muscles.
The paired muscles were separated at the midline, exposing the rectus capitis dorsalis
muscles. The caudal aspects of the rectus capitis dorsalis muscles were removed from the
cranial half of the second cervical vertebra and the muscle bellies were split at the
midline. The cranial aspects of the rectus capitis dorsalis muscles were then sharply
incised from the nuchal crest, exposing the caudal portion of the occiput and the arch
of the atlas.
The occiput and the dorsal aspect of the C1 vertebra were removed using a high-speed air
drill with round drill. The dorsal atlanto-occipital membrane was incised and expansile
duroplasty was performed by using artificial dura mater (Gore-Tex; Japan Gore, Tokyo,
Japan) (). Closure was routine. Postoperative
analgesia was performed appropriately by intramusucular administration of morphine
hydrochloride (0.5 mg kg-1 Morphine; Takeda, Osaka, Japan). Ventral fixation
of the atlantoaxial joint was performed to stabilize it on the 14th day after the first
consultation. Anaesthesia and analgesia were performed as in the previous surgery. The
dog was placed in dorsal recumbency with the neck hyperextended. A ventral midline skin
incision was made over the cranial half of the neck.
The sternohyoideus muscles were divided in the midline and the trachea and oesophagus
were retracted toward the dog’s left side. The larynx was also retracted toward
the left, once the attachments of the right sternohyoideus muscle were severed close to
the larynx. The thyroid gland, recurrent laryngeal nerve, right vagus, and carotid were
identified and protected throughout the surgery. The longus colli muscle was elevated
from the ventral surface of the axis and atlas and retracted.
Two threaded-pins (0.9 × 75 mm; IMEX, Tokyo, Japan) were placed across each of
the ventral articular facets between the axis and atlas. Then, removal of cartilage of
the atlantoaxial joint and autografting of cancellous bone collected from the humerus
were performed to create bone union at the atlantoaxial joint. Finally, implanted pins
were fixed by using bone cement (Osteobond; Zimmer, Tokyo, Japan) ().
The dog stood and walked by herself and left the medical centre. Ventro-dorsal
radiograph of the cervical region in 134 days after the first consultation revealed no
loosening of thread pins and bone cement ().


A 46-year-old male was referred to the infectious diseases department with an acute rise of liver enzymes during routine laboratory evaluation (Table ). His past medical history revealed tuberous sclerosis complex, for which he was treated with sirolimus since 2007 due to the progression of subependymal giant cell astrocytoma and multiple renal angiomyolipomas. This was switched to everolimus (10 mg per day) in 2013 after two registration studies had shown its safety and efficacy for these indications [, ]. At presentation (in 2015), the patient had suffered fatigue and weight loss of 5 kg during the preceding 3 months. There was no icterus, nausea or fever. A thorough food history was taken, but revealed no obvious route of transmission, such as the consumption of red meat, wild boar or deer. The patient did report consumption of well-cooked pork in the past. There was no history of blood transfusions. The patient had lived his entire life in a non-endemic country with good sanitary hygiene and there was no history of travelling abroad. Physical examination was normal and the liver was not palpable. An active HEV infection was diagnosed though serum polymerase-chain-reaction (PCR; nucleic acids were extraction with MP96 system; Roche Diagnostics, Germany; and primers and probes based on Zhao et al. []) with a cycle time of 23.41 cycles (amplification by a Taqman 7500 instrument; Applied Biosystems). After diagnosis, spontaneous clearance was awaited for a period of 3 months. However, since no spontaneous clearance occurred (PCR positive, cycle time 25.54), everolimus therapy was discontinued. Subsequent re-evaluation after another 3 months showed negative serum PCR and normalization of liver enzymes. Hereafter, everolimus therapy was restarted and no rise of liver enzymes was seen during more than 1 year follow-up (Fig. ). During everolimus discontinuation, the patient had no complaints indicating progression of the giant cell astrocytoma. Additionally, computed tomography of the brain and kidneys following restart of everolimus therapy showed no progression of the brain tumor nor of renal angiomyolipomas.


A 32-year-old male presented with a hyperpigmented lesion over the right leg noted since 3 years. Dermatological examination revealed a hyperpigmented ichthyotic plaque measuring 30 cm × 15 cm covering the anterolateral aspect of the right leg []. Neurological examination revealed an impairment of temperature, touch and pain sensations over the lesion, and thickening of the common peroneal nerve on the right side. Right-sided foot drop was present. Based on these clinical features, a provisional diagnosis of Hansen's disease was made and investigated further.
Routine biochemical parameters were within normal limits except for high serum lactate dehydrogenase. Slit skin smear for acid fast bacilli was negative. Skin biopsy showed a diffuse infiltrate of pleomorphic small and medium sized lymphocytes in the dermis extending up to the subcutis []. On immunohistochemistry, the cells were found to be positive for CD3 [] and CD4 and negative for CD8, CD20, and CD30. The features were consistent with the diagnosis of primary cutaneous CD4 + pleomorphic small/medium-sized T-cell lymphoma.
We proceeded to investigate further to explore the prominent nerve thickening noted clinically in this patient. Nerve conduction study showed evidence of demyelination in the common peroneal nerve and electromyography showed normal motor potentials with no evidence of axonal degeneration. Magnetic resonance imaging of right lower leg revealed thickening of the common peroneal nerve. To avoid further nerve damage to the motor nerve, we opted for ultrasonography-guided fine needle aspiration cytology (FNAC) of the common peroneal nerve instead of biopsy, which revealed atypical lymphoid cells with irregular nuclei, coarse clumped chromatin and scanty cytoplasm []. Peripheral smear, cerebrospinal fluid analysis, bone marrow study and computed tomography scans of the abdomen, thorax and brain were normal. Serological tests to detect infection with human T-lymphotropic virus 1, human immunodeficiency virus and Borrelia burgdorferi were negative. Based on these results, a diagnosis of NL secondary to primary cutaneous CD4 + pleomorphic small/medium-sized T-cell lymphoma was made. The patient received six cycles of cyclophosphamide, doxorubicin, vincristine, prednisone regimen consisting of cyclophosphamide, hydroxydaunorubicin (adriamycin), oncovin (vincristine), and prednisolone and localized radiotherapy. On the follow-up, there was a significant decrease in the size of the cutaneous lesion, marked improvement in foot drop, markedly reduced infiltrate in skin biopsy. There was no evidence of relapse in 3 years follow-up period.


Written informed consent was obtained from the patient for the publication of this case and accompanying images.
A 47-year-old female presented with an 8-year complaint of difficulty falling asleep and waking up in the morning. The patient was consequently unable to maintain stable entrainment to a 24-h sleep–wake pattern. She visited our hospital (Tokyo Women’s Medical University Hospital) for the first time in August 2004 and was diagnosed with MDD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria, exhibiting depressed mood, markedly diminished interest, and loss of energy. The patient had no history of problems with the use of alcohol and other substances. Pharmacological treatment with antidepressants, including paroxetine, milnacipran, fluvoxamine, and duloxetine, was administered alternately. However, her depressive symptoms showed repeated exacerbation, and she was unable to work regularly. After a 3-month period of hospitalization for depression in 2007, the patient stopped working and exhibited social withdrawal. The patient exhibited depression with moderate severity, as indicated by a Clinical Global Impression-Severity scale (CGI-S) score of 4.0. The moderate depressive state continued from that time.
At the age of 40 years (in 2009), the patient’s sleep–wake cycle began to extend, independently of changes in depressive symptoms. In December 2014, she was diagnosed with N24SWD using the International Classification of Sleep Disorders, Third Edition (ICSD-3). At that time, she was taking 40 mg/d of duloxetine (in the morning), but no other antidepressants or sedatives/hypnotics. Ramelteon 8 mg/d (at 7 PM) was administered, and sleep hygiene education was provided, but these treatments did not positively affect circadian dysregulation. In June 2015, the patient began taking melatonin 1 mg/d (at 7 PM), but this treatment also had no effect. Calculated from sleep onset and offset time using sleep diary data between September 2014 and November 2015, the mean (standard deviation [SD]) time of the patient’s sleep, awake, and sleep–wake cycle were 12.9 (5.2), 20.5 (7.3), and 33.4 (10.2) h, respectively. In December 2015, aripiprazole 3 mg/d (after morning meal) was administered, primarily to improve the loss of energy. After treatment for 4 weeks (in the middle of January 2016), the patient’s sleep–wake cycle had become markedly synchronized to the environmental light–dark cycle. Subsequently, the patient fell asleep between 12 midnight and 3 AM and awoke between 8 AM and 11 AM (), similar to her sleep–wake pattern before she was diagnosed with N24SWD. Although the patient’s depressive symptoms, including loss of energy, were not improved by treatment with aripiprazole (a CGI-S score of 4.0), her sleep–wake cycle remained synchronized on the same dose of aripiprazole for at least 6 months, and the mean (SD) time of the patient’s sleep, awake and sleep–wake cycle were 9.9 (2.1), 14.3 (2.7) and 24.2 (3.0) h, respectively (calculated using sleep diary data between February 2016 and July 2016).


An 18-year-old male patient presented with a painful snap over the lateral aspect of his knee whenever he flexed his knee and low grade ache over the lateral side of the knee following sitting down/squatting. He worked as a manual labourer and was a club level basketball player. He could consistently reproduce a clearly audible snap by contracting his biceps femoris muscle with the knee in between 80° and 100° of flexion. The symptoms had started spontaneously around 12 months back without any specific trauma, and had been getting worse over the past 6 months. It was preventing him from playing a sport and doing his job that involved squatting. He was initially treated conservatively by avoidance of activities that precipitate the symptoms; however, he was not responsive to physical therapy for 6 months and then symptoms got worse. He was not able to play basketball for 6 months, and had not been working for the last 3 months. His knee examination was normal except for a palpable movement of the biceps femoris tendon over the fibular head when the knee was taken through 80°–120° of flexion. The biceps tendon could be easily palpated and passively moved anteriorly and posteriorly over the fibular head, reproducing mechanical irritation in the distal tendon. Radiography and magnetic resonance imaging scans did not demonstrate any abnormality.
The patient was given a general anaesthetic and was positioned supine with the knee at 60° of flexion against a foot and thigh bolster. A 5 cm incision was made in line with the biceps tendon over the fibular head, ending at Gerdy’s tubercle. Superficial and deep dissection exposed the common peroneal nerve at the level of the neck of the fibula, and a neurolysis was performed from the fibula neck back under the biceps tendon and into the posterior compartment of the thigh. The terminal insertions of the biceps tendon were then carefully exposed and examined. In Terry and LaPrade descriptions, the main tendon of the long head divides just proximal to the fibular head and gives an insertion to the posterolateral edge of the fibular head just posterior to the LCL insertion (the “direct arm” of the long head) before continuing on as a thinner anterior arm that ends by blending with aponeurosis of the anterior compartment of the leg as well as giving some deep fibres of its own to the lateral edge of the fibula, thus making a sling with the direct arm encompassing the LCL insertion (). In our case, it was the direct arm that was thin and relatively deficient, and the anterior arm was hypertrophic, cordlike, and inserted into the anterolateral fascia on the tibia that blended with the Gerdy’s tubercle over the ITB insertion ( and ). It was this thickened cord that moved from superior to the fibular head to inferior to the fibula as the knee was flexed, causing a loud “snap” as it flicked over the prominence of the fibular head at that ROM. There was also a hypertrophic lateral prominence of the fibular head.
The insertion of this hypertrophic anterior arm was carefully detached () from the tibia and a No. 5 Ethibond (Ethicon, Somerville, NJ, USA) suture was whip stitched on its distal 20 mm. The whipstitching involved taking five throws on either side of the detached tendon with 10 cm of two free suture ends at the distal most aspect of the tendon from where it was detached much like whipstitching hamstring tendons in an anterior cruciate ligament reconstruction. The prominent posterior-lateral border of the fibular styloid was identified and removed using a small osteotome () and a rongeur was used to obtain a smooth edge. Using a guide wire and a 7 mm reamer, a socket was drilled through the fibular head. The detached portion of the biceps tendon was then shuttled through this tunnel using the free ends of the suture whipstitched on its terminal portion and tied to a metallic button () to dock it in the socket created. The knee was brought back into extension and as the biceps tendon was quite tight coming into full extension, it was lengthened slightly using a pie crusting technique. The knee could then be easily brought into normal hyperextension. The wound was closed with monocryl (Ethicon).
Postoperatively, the knee was put in a ROM brace blocking terminal 30° of extension and was mobilised non-weight bearing using crutches for 2 weeks. He was then rehabilitated to get full extension by prescribing active and active assisted exercises using a rolled towel under the heel with the knee in extension and asking the patient to extend the knee further. He was prevented from doing active hamstring contractions for 6 weeks: this was done by locking the knee in extension for 2 weeks while walking and releasing it at rest for passive flexion. At the 6 week mark, the ROM was normal, including slight hyperextension, and the patient was allowed to commence active hamstring contractions and gentle running. He returned to full sporting activities by 3 months after surgery and had a ROM of 0°–130°. At the one-year follow-up, the patient had a visual analog scale score of 0 and no recurrence of symptoms, and he was fully functional in day to day activities as well as playing club level basketball.


A 43-year-old female had a history of progressive blurred vision and recurrent corneal erosions since childhood. She presented with superficial honeycomb opacities in both eyes in May 2012 [ and ]. She and her two daughters had an Arg555Gln mutation in the TGFBI gene. The best-corrected visual acuities (BCVAs) were 20/200 with a refraction of +1.5 −0.75 × 30° in the right eye and 20/60 with a refraction of +0.25 −2.5 × 30° in the left eye. Central corneal thickness was 570 µm in the right eye and 600 µm in the left eye. Anterior segment-optical coherence tomography (AS-OCT) showed the highest opacity at the anterior cornea, about 150 µm in both eyes. Corneal topography (TMS-4, Tomey Corporation, Nagoya, Japan) showed surface regularity index (SRI) values of 1.18 and 1.34 and surface asymmetric index (SAI) values of 2.67 and 1.97 in the right and left eyes, respectively [ and ]. In August 2012, superficial LK and PTK were performed to remove the most superficial opacities in the right eye. Surgical techniques of LK employed 64 Beaver blade to remove epithelial and subepithelial opacities under topical 0.5% proparacaine anesthesia.[] To remove the residual superficial stroma opacities and smooth corneal surface, the following PTK was performed with the excimer laser machine (Technolas 217Z, Bausch and Lomb, Rochester, NY, USA). The laser was applied with an ablation diameter of 7.0 mm and an ablation depth of 80 µm. During the procedures, hypromellose (0.32%) was applied to smooth corneal surface irregularities. Mitomycin-C (0.02%) solution was applied for 10 s at the end of the surgery. Postoperatively, topical fluorometholone (0.1%), levofloxacin ophthalmic solution (0.5%), and hypromellose (0.32%) eye drops were administered four times daily. The histology of the removed corneal specimen showed a misalignment of epithelial cells and subepithelial deposition of fibrous tissue; these observations were consistent with the histological findings in TBCD. Postoperatively, most opacities of the right eye were removed, and the vision improved to 20/40 with a refraction of +4.00 −2.24 × 30° []. However, the patient experienced a mild glare, and the SRI and SAI increased to 1.52 and 3.68, respectively []. Ocular aberrometry was performed with an iDesign aberrometer (Advanced WaveScan aberrometer; Abbott Medical Optics, Santa Ana, CA, USA), and wavefront-guided PRK was performed using the VISX Star S4 IR excimer laser platform (Abbott Medical Optics, Santa Ana, CA, USA) with a 10 s application of 0.02% mitomycin-C solution. The laser treatment profile used the aberrometric correction of +4.45 −2.38 × 30° with an ablation of 6.0 mm for the optical zone and 1.5 mm for the transition zone. At postoperative month 4, the vision improved to 20/25 with a refraction of −0.50 −1.50 × 50° without glare. The postoperative SRI and SAI of the right eye decreased to 1.02 and 1.18, respectively. As the vision and glare of the right eye showed improvement, wavefront-guided PRK was repeated 5 months later. The postoperative vision improved to 20/20 with a refraction of −1.0, and corneal opacity decreased []. The SAI and SRI further reduced to 0.61 and 0.91, respectively [].
In April 2015, superficial LK and PTK were performed in the left eye with an ablation depth of 120 µm and an ablation zone of 6.0 mm. The left cornea became clearer; the BCVA was 20/50 with a refraction of +7.75 −0.50 × 10° postoperatively []. The post-PTK SRI and SAI increased to 1.35 and 3.12, respectively []. Due to a high hyperopic shift, wavefront-guided PRK was performed at 5 and 12 months postoperatively. Corneal opacity decreased, especially in the mid-peripheral area, and vision improved to 20/25 with a refraction of +0.75 −1.0 × 80° []. The SAI and SRI decreased to 1.07 and 1.89, respectively []. AS-OCT showed that most superficial opacities were removed in both eyes; the central corneal thicknesses were 436 and 431 µm in the right and left eyes, respectively. To date, no complication was found in our case after PTK and wavefront-guided PRK except the recurrence of faint superficial opacity in the right eye. The vision was still 20/20 in the right eye and 20/25 in the left eye. Since the visual acuity of the patient was still satisfactory, further treatment can be deferred. Similar PTK and wavefront-guided PRK settings could be repeated in the future if needed.


A 68-year-old male diagnosed with MMP presented with complaints of dryness in both eyes. On examination, his corrected distance visual acuity (CDVA) was 20/200 in the right eye and 20/100 in the left eye. The patient had been using topical carboxymethyl cellulose 0.5% (Optive, Allergan, Irvine CA, USA) four times a day, hydroxyl propyl methyl cellulose gel at night, and oral mycophenolate mofetil 1000 mg and cyclophosphamide 50 mg, both twice daily. He had received intravenous cyclophosphamide 50 mg infusion on multiple occasions previously. Slit lamp examination showed a symblepharon, shorting of the inferior fornix, meibomian gland dysfunction, and marginal corneal superficial vascularization in both eyes. An epithelial defect 2.5 mm × 1.5 mm in the right eye [] and 2 mm × 1 mm [] in the left eye was noted. A therapeutic contact lens (Air-Optix Aqua, Alcon, TX, USA) trial failed to heal the epithelial defect despite several attempts. The poor ocular surface caused the contact lens to dislodge frequently.
The patient was then fitted with a Rose K2 mini-scleral contact lens in an attempt to alleviate symptoms and promote healing. The lenses, made of Menicon Z, had a base curve of 6.60 mm, diameter of 14.6 mm, and power of −5.50 D for both eyes. He was advised to wear them during the waking hours and to switch to soft contact lenses at night. He was asked to soak them in Boston Simplus solution (Bausch and Lomb, Rochester, NY, USA) and clean the lens periodically. Rapid reepithelization was observed, and the size of corneal epithelial defect decreasing to 1.5 mm × 1 mm within 4 days [–] and 0.5 mm in 8 days [–] in both eyes. Complete resolution of the epithelial defect was seen after 4 weeks in both eyes [–]. In addition, the CDVA improved to 20/50 in the right eye and 20/40 in the left eye. The patient's visual acuity and corneal surface integrity have remained stable for 6 months of follow-up. He is currently on topical lubricants and tablet endotoxin 100 mg once daily.


A 54-year-old female JW patient (body weight, 50 kg) diagnosed with liver cirrhosis complicated by hepatitis B viral infection presented to the bloodless center in our institute to assess whether LDLT was possible. She had massive ascites without encephalopathy, but was in good physical condition otherwise. Initial laboratory findings were hemoglobin (Hb) of 8.1 g/dl, platelets 51 × 109/L, prothrombin time (PT) 1.65 (international normalized ratio, INR), albumin 2.1 g/dl, creatinine 1.5 mg/dl, and total bilirubin 3.04 mg/dl. We discussed with a surgeon the possibility of LT without transfusion. Acceptable transfusion alternatives were confirmed after discussion with the Jehovah's Witnesses Hospital Liaison Committee and the patient. The patient refused to receive any red blood cells (RBCs), fresh frozen plasma, or platelet concentrate, but agreed to receive human albumin, recombinant factor VIIa and VIIIa, fibrinogen concentrate, cryoprecipitate, and intraoperative cell salvage (ICS) via a continuous circuit to the patient's circulation. She also accepted reinfusion of collected whole blood acquired from acute normovolemic hemodilution (ANH) provided via a continuous circuit. The organ transplantation ethics committee then met to decide whether those surgical restrictions were ethically acceptable because this was the first LT in an adult JW patient in South Korea. Following committee approval, the patient decided to undergo LT. Her son, who is not a JW, chose to donate his right hepatic lobe.
Erythropoiesis-stimulating agent (ESA) therapy with recombinant human erythropoietin (rHuEpo) and intravenous iron was initiated along with folic acid and vitamin B12 to increase the patient's red cell mass. Subcutaneous rHuEpo (Epokine®, CJ HealthCare, Seoul, Korea) at 10,000 IU and intravenous iron (Venoferrum®, JW Pharmaceutical, Seoul, Korea) at 200 mg were administered three times per week. After 9 weeks' administration, the Hb level increased to 13.1 g/dl and the patient was scheduled for surgery the next day. On arrival at the operating theater, monitoring was initiated with a five-lead ECG, noninvasive blood pressure cuff, pulse oximeter, and bispectral index sensor. Anesthesia was induced with propofol at 80 mg and, after the administration of rocuronium at 50 mg, the patient was intubated. Anesthesia was maintained with oxygen, air, desflurane, and continuous remifentanil and rocuronium infusion.
Hemodynamic monitoring included the right radial and femoral artery pressures, central and right femoral vein pressures, pulmonary artery and capillary wedge pressures, and cardiac output measurements via a Swan-Ganz catheter. A transesophageal echocardiography probe was inserted to monitor volume status and systolic function and to diagnose the cause of any sustained hypotension that occurred during surgery. The right radial artery was used for blood sampling and drainage of the patient's blood for ANH. After vascular catheterization, ANH was initiated. The patient's blood volume was estimated at 3,000 ml (60 ml/body weight, kg). The target Hb level was approximately 10.0 g/dl. We collected 960 ml of whole blood for ANH, which was divided into three CPDA-transfusion bags (320 ml each), while maintaining continuous infusion to the patient via the radial artery catheter. Briefly, we did not replace blood loss with fluid simultaneously as is usually done in ANH. No fluid was administered until after collection of the first 500 ml whole blood to prevent dilution of RBC, coagulation factors, and platelets. Thereafter, 750 ml 5% Albumin® (Green Cross Corp., Yongin, Korea) and 500 ml Plasma Solution A® (CJ HealthCare, Seoul, Korea) were administered to replace lost blood until ANH was completed. It took 15 min to obtain each unit. There were no changes in mean arterial pressure, heart rate, mixed venous oxygen saturation (SvO2, maintained around 90%), or cardiac output during 45 min of ANH. Central venous pressure (CVP) decreased by 1 mmHg from the initial value of 4 mmHg. Pre-ANH Hb was 13.4 g/dl, platelets 32 × 109/L, and fibrinogen 113 mg/dl. Post-ANH Hb was 10.8 g/dl, platelets 29 × 109/L, and fibrinogen 82 mg/dl. To prevent fibrinolysis, 40 mg/kg tranexamic acid was administered intravenously for 20 min before the surgical incision and then continuously infused at a rate of 10 mg/kg/h. All blood from the surgical field was salvaged using a cell saver until biliary anastomosis was initiated. Plasma Solution A® was administered at a rate of 5 ml/kg/h during the surgery. Blood loss was replaced with Plasma Solution A® at a 1 : 3 ratio throughout the surgery unless there was sudden blood loss, which was replaced by 5% Albumin® at a 1 : 1 ratio. CVP was maintained at less than 5 mmHg throughout the dissection phase. Norepinephrine (0.1 to 0.27 µg/kg/min) was used as a primary vasopressor to maintain the mean arterial pressure at 65 mmHg or above. During the pre-anhepatic phase, approximately 7,300 ml ascitic fluid was drained. Acute hemorrhage occurred when the inferior vena cava was injured during mobilization of the diseased liver, which caused 350 ml of blood loss until prompt hemostasis using a total inferior vena cava (IVC) clamp. We began to transfuse salvaged blood approximately 1 h after starting surgery to maintain the hemoglobin level at around 9 g/dl. One hour after beginning the anhepatic phase, ANH blood was retransfused slowly from the recently collected blood, as is recommended within 6 h of collection. The Hb level was maintained above 9 g/dl until the end of the surgery. Fibrinogen decreased to 56 mg/dl 3 h postoperatively. Fibrinogen concentrate (Fibrinogen Inj®, Green Cross Corp., Yongin, Korea) at 3.0 g was administered intravenously, which increased the fibrinogen concentration to 136 mg/dl.
There was no fibrinolysis on thromboelastography or oozing in the surgical field during the operation. Graft reperfusion was accomplished without any cardiovascular instability. SvO2 remained high during the entire operation, suggesting that there was no global oxygen supply/demand imbalance. The operation concluded uneventfully and the patient was transferred to the intensive care unit (ICU) while intubated. The total anesthesia duration was 8 h and the operation time was 6.6 h. Total blood loss was 940 ml. Plasma Solution A® at 4,800 ml, 5% Albumin® at 1,000 ml, and 470 ml of salvaged blood were administered. Urine output was around 900 ml.
Postoperatively, Hb was 11.9 g/dl, platelets 19 × 109/L, PT 2.49 INR, and fibrinogen 122 mg/dl (). The postoperative recovery was uneventful and the patient did not receive any blood products. She was discharged on postoperative day 15 without any complications. She is still in good health 5 years after surgery


A 47-year-old male JW patient suffering from alcoholic liver cirrhosis presented for LDLT. He had diabetes that was controlled with insulin and was administered ESA therapy with rHuEpo, which increased his hematocrit in preparation for bloodless surgery. After 27 episodes of ESA therapy over the six months before LDLT, the Hb level increased from 7.4 to 10.8 g/dl. Preoperative evaluations (echocardiography, pulmonary function test, esophagoduodenoscopy, chest radiography, and electrocardiogram) were within normal limits. Laboratory tests revealed Hb of 10.8 g/dl, platelets 46 × 109/L, PT 1.84 INR, fibrinogen 159 mg/dl, and albumin 3.2 g/dl.
Anesthesia was induced with pentothal sodium at 400 mg, and after administration of vecuronium at 10 mg, the patient was intubated. Anesthesia was maintained with oxygen, air, and sevoflurane. Hemodynamic monitoring included the right radial and femoral artery pressures, central and right femoral vein pressures, pulmonary artery and capillary wedge pressures, and cardiac output measurements via a Swan-Ganz catheter. Despite insertion of the Swan-Ganz catheter, cardiac output was not checked, so we monitored only SvO2. To maintain the body temperature during surgery, fluid was heated with a Level 1® Fast Flow Fluid Warmer (Smiths Industries, Rockland, MA, USA) and peripheral vascular access was blocked to prevent infusion of cold fluids.
During the intraoperative period, vecuronium was infused continuously (1.0 µg/kg/min) and sevoflurane was replaced with isoflurane after positioning the retractor. We regulated the concentration of isoflurane while aiming for 40 to 60 on the bispectral index. During the pre-anhepatic phase, there were no ascites and 500 ml of Hextend® (CJ HealthCare) was infused. We used regular insulin because the patient's glucose was 219 mg/dl and dopamine (5.0 µg/kg/min) was administered continuously for hemodynamic stability. Arterial blood gas analysis was performed every 1 h to monitor the Hb level. The authors administered 300 ml salvaged blood whenever the Hb level dropped below 9 g/dl. The lowest Hb level was 6.7 g/dl during the anhepatic phase. Continuous infusion of norepinephrine (0.05 µg/kg/min) was started before reperfusion and tranexamic acid at 500 mg was injected twice during the anhepatic and postreperfusion phase. There was no evidence of fibrinolysis on thromboelastometry, which was monitored at least every 2 h during surgery. To reduce blood loss, we used ICS except during biliary opening until the end of surgery. To conserve fluid effectively, we wrung out the gauze pads prior to removing them from the abdominal cavity.
During the 12 h and 30 min of surgical time, 8,300 ml Plasma Solution A®, 2,050 ml 5% Albumin®, 900 ml half normal saline, 1,000 ml Hextend®, and 2,065 ml of salvaged blood were infused. Urine output was 570 ml and estimated blood loss was about 2,500 ml. After surgery, the patient was transferred to the ICU while still intubated with continuation of dopamine (5 µg/kg/min) and norepinephrine (0.2 µg/kg/min).
The last blood test before the end of anesthesia revealed Hb of 10.5 g/dl, platelets 39 × 109/L, PT 7.75 INR, and fibrinogen 49 mg/dl (). The patient was extubated on the first postoperative day. Although he could not receive a transfusion of fresh frozen plasma or cryoprecipitate, PT was decreased and fibrinogen was increased with 2.18 INR and 211 mg/dl, respectively about 7 days after LDLT.
On postoperative day 17, leakage of the hepaticojejunostomy and small bowel perforation were suspected, so the patient underwent a second operation for resection and anastomosis of the small bowel. Continuous renal replacement therapy was initiated and maintained until postoperative day 28. He was transferred to the ward 36 days after LDLT, but was reintubated and transferred to the ICU on postoperative day 60 due to hypotension and respiratory failure. He died on postoperative day 76 due to several complications including intra-abdominal infection, pneumonia, and chronic renal failure.


A 71-year-old Caucasian male patient sought medical care complaining of a 4-month history of exertion dyspnea and edema of the lower limbs. His past medical history included hypertension and congestive heart failure, and although he had been abstinent for 1 year, he had previously smoked 75 packs/year. On physical examination he was hypotensive and cyanotic; his pulse was arrhythmic; he had edema of the lower limbs; he had bulging jugular veins when in the supine position; there were rales in the lower two-thirds of both lungs; and tender hepatomegaly was present. The electrocardiogram showed atrial fibrillation, and the echodopplercardiogram estimated the left ventricle ejection fraction of 63% (Teicholz), eccentric left ventricular hypertrophy, marked mitral insufficiency, and a left atrium of 85 mm. Pulmonary systolic pressure was estimated at 62 mmHg with marked tricuspid valve insufficiency. There were no valvular morphological abnormalities. He was hospitalized with the diagnosis of hypertensive cardiomyopathy and cor pulmonale.
He also complained of vision loss for 2 months accompanied by protrusion of the right eye globe. The ophthalmologic examination in the right eye revealed marked corneal deepithelization and edema, ocular protrusion, the absence of photomotor and consensual reflexes, and low visual acuity. The left eye was normal. Brain computed tomography and cranial magnetic resonance imaging (MRI) confirmed the presence of a neoplastic lesion infiltrating the paranasal sinuses and the frontal encephalic lobe (). A tumoral biopsy was scheduled, but the patient died before the procedure could be done because of a refractory cardiogenic shock.
Autopsy findings included marked cardiomegaly with four-chamber dilation; the interventricular septum measured 18 mm, and the ventricular wall (posterior, anterior, and lateral) measured 15 mm. Radiological findings were confirmed at autopsy as a metastatic lesion most probably from an epithelial neoplasm of the esophagus. A 2 cm wide ulcerated lesion was found in the middle third and other lesion with a vegetating appearance measuring 1 cm in the upper third of the esophagus () The tumor infiltrated the submucosa, muscular ( and ), and adventitia layers and adhered to the paraesophageal structures mainly at the esophageal-ulcerated lesion.
The histological examination showed a small-cell neuroendocrine carcinoma of the esophagus, since AE1/AE3 positive and synaptophysin () were positive.
Metastatic involvement was found in the paranasal sinuses, the muscles around the right eye, the orbital bones (), the meninges, the right frontal lobe, the liver, the adrenal glands, and the pericardium.


An 86-year-old female with past medical history of right hip replacement in 2015 was brought to emergency room (ER) by emergency medical services (EMS) after her granddaughter found her in altered mental status. Patient had been not feeling well for 2 days before the presentation. Patient had not visited to her primary medical doctor for a long time. Her last hospital visit was 4 years ago for orthopedic admission. There was no history of alcohol use, smoking or use of recreational drug. Patient denied following specific dietary pattern. There was no history of any numbness, tingling or difficulty in walking. There was no history of alteration in the bowel or bladder habit, weight loss, or gastric or small bowel surgery.
This was the first episode of such symptoms. Granddaughter endorsed that the patient was not taking any medication and had no significant family history. Patient was intubated in the ER due to respiratory distress and altered mental status. Patient had tachycardia and tachypnea. Her pulse was 110 bpm, blood pressure (BP) was 148/100 mm of Hg, respiratory rate was 32 per minute and was saturating at 80% in 6L on face mask. On examination, patient was dehydrated. She had no evidence of trauma. Chest examination revealed rapid shallow respiration with wheezing. Besides mild pedal edema, there were no other significant physical examination findings.
Initial investigation revealed white blood cell (WBC) count of 6.5 × 103 per µL with normal differential count. Hemoglobin was 3.2 gm/dL (12–16), hematocrit 9.6% (36–46), mean corpuscular volume (MCV) 127 fL (80–100) and platelets 59 × 103 per µL (130–400). Retic count was 7.5% (0.5–1.5) with corrected retic of 1.6%. Lactate dehydrogenase (LDH) was 7077 IU/L (98–192). Haptoglobin level was very low (14 mg/dL).
Serum electrolytes were within normal limits. Arterial blood gas showed severe metabolic acidosis with high anion gap (29 mmol/L). Renal functions were impaired with blood urea nitrogen (BUN) and creatinine of 34 mg/dL (8–20) and 1.9 mg/dL (0.4–1.3), respectively. Serum glucose was 93 mg/dL, osmolality was 308 mOsm/L and lactic acid 20.3 mmol/L (0.5–1.9). Liver function test revealed hyperbilirubinemia with total bilirubin of 3.7 mg/dL (0.3–1.2), direct bilirubin of 1 mg/dL, aspartate transaminase 51 IU/L, alanine transaminase 22 IU/L and alkaline phosphatase of 41 IU/L. Her brain natriuretic peptide (BNP) was 670 pg/mL (0–100). Troponin was negative. Her international normalized ratio (INR) was elevated (2.48) with prothrombin time (PT) and activated partial thromboplastin time (aPTT) of 29 and 24 s, respectively. Toxicology screen was negative for ethylene glycol, salicylates and alcohol. Serum ketones were negative.
Imaging scans were negative except mild cardiomegaly on chest x-ray. Computed tomography (CT) of head and abdomen was negative. CT with pulmonary embolism (PE) protocol was negative for PE. She was admitted to intensive care unit (ICU) for altered mental status, multi-organ dysfunction syndrome with severe metabolic acidosis in setting of hemolysis. She was managed with intravenous antibiotics and blood transfusion. Patient received 3 units of blood. Patient improved significantly after blood transfusion. Lactic acid normalized within 10 h of admission. Antibiotics were discontinued when culture reports were negative. Acute kidney injury resolved and mentation improved after transfusion. She was weaned off ventilator in 2 days.
Fecal occult blood tests were both negative. Ferritin was 588 ng/mL (15–150), total iron-binding capacity (TIBC) 194 µg/dL (250–450), transferrin 155 mg/dL (200–370) and iron saturation 91% (15–55). Peripheral smear showed large red blood cells (RBCs) with hypersegmented (6–7 lobes) neutrophils with 1% schistocytes, poikilocytes and anisocytosis ( and ). Anemia work-up revealed mixed picture of megaloblastic anemia and hemolytic anemia.
Further work-up for anemia revealed that vitamin B12 was 38 pg/mL (211–946), methylmalonic acid 753 nmol/L (0–378), homocysteine 99.3 µmol/L (0–15), anti-parietal antibodies 21.7 units (0–20) and anti-intrinsic factor antibodies 4.7 AU/mL (0–1.1). Direct and indirect Coombs tests were negative, fibrinogen was 185 mg/dL (193–507) and D-dimer was 5170 ng/mL (0–500). Serology was negative for HIV and hepatitis virus. Patient was diagnosed with pernicious anemia and pseudo-TTP with concomitant intramedullary hemolysis.
Patient was started on parenteral vitamin B12. Her hematological parameters and her clinical condition improved significantly after starting therapy with cyanocobalamin. Her blood parameters at the time of presentation and at the time of discharge are shown in .


A 73-year-old male presents with a 5-week history of nausea, vomiting, and abdominal pain. Past medical history is significant for stage IV transitional cell cancer with angiolymphatic invasion treated with neo-adjuvant chemotherapy and radiation followed by radical cystectomy with ileal conduit formation and bilateral pelvic lymphadenectomy. He had also undergone a diverting sigmoid colostomy for rectal outlet obstructive symptoms from metastases to the rectum. Subsequent surveillance imaging and colonoscopies were negative for any recurrence as recent as nine months prior to the current symptoms.
For the abdominal pain, patient was evaluated with CT of the abdomen and pelvis which revealed new circumferential thickening and inflammatory stranding involving the ascending colon extending to the hepatic flexure as well as the descending/transverse duodenal junction with adjacent inflammatory stranding (Figs. and ). Diffuse intra- and extra-hepatic biliary ductal and main pancreatic duct dilatation (double duct sign) was noted as well. Transaminases and bilirubin were initially normal.
Magnetic resonance imaging (MRI) of the abdomen was pursued to further investigate the double duct sign, which did not reveal choledocholithiasis or pancreaticobiliary malignancy. The dilated biliary tree was suspected to be secondary to thickened descending duodenum. This thickening was abutting the hepatic flexure. Additional findings included hydroureteronephrosis on the right with a focally enhancing soft tissue mass (Fig. ).
Upper endoscopy for evaluation of gastric outlet obstruction demonstrated duodenal stenosis with significant edema and congestion without an obvious ulcer (Fig. ). The stenosis could be traversed only with an ultrathin endoscope but biopsies were nondiagnostic. Based on the MR imaging findings, endoscopic evaluation of the colon was pursued in hope of getting a better yield for diagnosis. Colonoscopy demonstrated a mass at the hepatic flexure (Fig. ). Biopsies confirmed invasive transitional cell cancer. Patient underwent a Wall Flex (22 mm × 120 mm) metal stent to help alleviate the gastric outlet obstruction (Fig. ). Chemotherapy was planned by oncology. Patient had progressively deteriorated and expired one month later after establishing an agreement on comfort care only.


A 42-year-old man was admitted to our hospital for assessment of chronic watery diarrhea. His complaint had been started about 8 months earlier and progressed by time. The frequency was 8 to 10 times per day without pain or bloody diarrhea, which was aggravated by eating but was constant during fasting and could awake him during sleeping. He had 20 Kg weight loss during this time and recently he complained of progressive fatigue and walking disability. months ago, he also had been assessed for this problem and underwent diagnostic laboratory tests (table1). Upper and lower gastrointestinal (GI) endoscopy with biopsy at that time was normal. To rule out Zollinger Ellison syndrome, fasting gastrin serum was performed, which was 35 pg/mL and octeroscan was normal. Empirical therapy with metronidazole and ciprofloxacin was started with the impression of blind loop syndrome but his condition did not improve.
In his medical history, he had abdominal pain, postprandial vomiting, and weight loss about 2 years ago. He had undergone gastrojejunostomy for the treatment of bowel obstruction due to duodenal ulcer. He did not have a history of travel, recurrent infections, and high risk sexual contact. He was married and did not have a history of any significant diseases in his family.
In physical examination, he was pale and cachectic. His vital signs were normal. No lymphadenopathy, thyromegaly, heart murmur, and abnormal sound in lung were detected. The abdomen was soft with midline surgical scar without tenderness and organomegaly. In neurological examinations he had proximal weakness in his four limbs. Mild pitting edema was detected in lower extremities. Other exams were normal.
The results of laboratory tests on admission are shown in the table. Significant findings were sever hypokalemia (K=1.8 mmoL/L), mild anemia (Hgb=11 g/dL) and low serum albumin level (Alb=2.8 g/dL). Stool exam was normal. Sudan ш staining and stool collection for the measurement of fat were not be performed.
Abdominal computed tomography (CT) with contrast was normal. Transit of small bowel showed rapid transit time in small bowel and bypass of some parts of it ().
According to the result of upper GI series, after correction of potassium abnormality and improving the nutritional status with total parenteral nutrition (TPN), we scheduled him for exploratory laparotomy. During the surgery, a 5-cm fistula was detected between the inferior wall of the body of stomach and transverse colon. The repair of gastrocolic fistula was performed in one-stage surgery.
He was discharged from the hospital 7 days after surgery without any complaint of diarrhea. During 6 months follow-up, he was in remission and had about 10 kg weight gain.


The patient was a 19-year-old African American woman who underwent uncomplicated full-thickness-penetrating keratoplasty in her right eye (OD) for advanced keratoconus. One week after surgery, she sustained a blunt trauma to OD that resulted in graft dehiscence from 3 to 5 o'clock, which was repaired surgically. Postoperatively, she received a topical steroid (prednisolone) 4 times a day tapered to 3 times a day at 3 months. Four months after surgery, her uncorrected vision was 20/60 in OD, with 6 dpt of against-the-rule astigmatism. Two corneal sutures were removed with the guidance of topography. Four days later, the patient presented with redness, irritation, and sudden decrease in vision in OD to count fingers at 2 feet with intraocular pressure (IOP) of 11 mm Hg. Corneal examination showed diffuse haziness with stromal edema, Descemet membrane folds, and an incomplete Khodadoust line (Fig. ). A diagnosis of acute corneal rejection was made. Intravenous pulse methylprednisolone (Solu-Medrol), 1 g daily for 3 days, was initiated, in addition to an hourly topical steroid (prednisolone). At 3 days after initiation of treatment, the patient was seen to have progression of the Khodadoust line and no improvement in graft rejection. At that point, a 1-mL subtenon injection of 40 mg/mL of triamcinolone was placed in the superotemporal quadrant. The patient was asked to continue topical steroid drops and was started on oral prednisone, 60 mg/day. Seen a week later, she showed improvement in vision to 20/80 in OD, although it was fuzzy according to the patient. There was a remarkable clearance of corneal edema and improved clarity in the superior half of the graft, with the inferior half remaining hazy (Fig. ). IOP was 16 mm Hg. The patient was observed for another week with no further improvement. On the basis of the response to the initial subtenon triamcinolone injection, she received additional injections of 0.5 mL of triamcinolone (40 mg/mL) in the inferonasal and inferotemporal quadrants. Four days later, the corneal graft rejection had completely resolved, with no keratic precipitates and with complete resolution of corneal edema and haze (Fig. ). Her vision improved to 20/50, and IOP remained stable at 14 mm Hg. Topical prednisolone was decreased to 8 times a day for 2 weeks and subsequently to 4 times a day. Oral prednisone was tapered to stop. At her last follow-up, 5 months after the injections, the corneal graft remained clear.


A 42-year-old Saudi male presented to our emergency room with a history of upper gastrointestinal bleeding in form of hematemesis and melena for 1 day prior to his presentation. It was preceded by 2 days of persistent nausea and repeated vomiting. He denied symptoms of chronic dyspepsia, NSAIDs or alcohol consumption. There was no history of abdominal trauma or background of chronic liver disease. Upon assessment, he was fully conscious, oriented, nonicteric, and dehydrated, with no peripheral or central stigmata of chronic liver disease. Two hours after the arrival, he experienced another attack of hematemesis, a total amount of around 150 mL. Room air oxygen saturation was maintained at 98%, his pulse was 110 beats/min, and his blood pressure was 102/68 mm Hg. There was no significant postural drop of blood pressure. Chest examination showed a decreased air entry in the right lower zone. Cardiovascular system examination was within normal limits. His abdomen was soft with mild epigastric tenderness; there was no rigidity or rebound tenderness. His initial routine laboratory test is presented in Table . After the patient's condition had been stabilized with initial resuscitation, blood transfusion was carried out and PPI infusion was initiated. Urgent gastroscopy revealed a normal esophagus; the stomach was obscured with fresh blood and blood clots, and intubation of the pylorus was difficult due to anatomical distortion (organoaxial volvulus). However, intubation of the pylorus achieved after several attempts. The second part of the duodenum was partially compressed with normal mucosa. Gastric (fundal) mucosa was severely inflamed with variable sizes of multiple ulcers (Fig. ). Some of them were actively oozing blood, which required adrenaline injection to achieve homeostasis. The patient was admitted to the intensive care unit and observed closely for any clinical deterioration, sign of perforated viscus or peritonitis. Chest X-ray (Fig. ) showed a raised right hemidiaphragm with homogenous haziness in the right lower lung lobe and obliteration of the right costophrenic angle. Erect abdominal X-ray showed a dilated stomach with an air/fluid level and a gas-filled bowel loop behind the cardiac shadow blunting the cardiophrenic recess (Fig. ). Contrasted CT scan was carried out early after recovered acute renal injury and revealed pancreatitis with prepancreatic collection (Fig. ), splenic vein thrombosis and intrathoracic herniation of the fundus of the stomach, antrum, and pylorus bowel loop along with an omentum into the posterolateral segment of the chest cavity (Fig. ). Pancreatitis was assumed to be related to impaired blood flow and pressure effect. A surgical approach was considered early. The patient was kept under very close observation in the intensive care unit.
His clinical and biochemical parameters improved and a second endoscopy evaluation was done after 5 days of admission showing that the previous gastric ulcers had significantly healed. He was subjected for corrective reconstructive surgery. Surgical intervention was done through a thoracotomy approach to reduce the abdominal content and repair the hernial defect. His postoperative course was smooth. Postoperative chest X-ray (Fig. ) was almost normal. He was discharged a few days after surgery with complete clinical recovery.