A 48-year-old man with a recent history of epigastric pain was referred to the Department of Integrated Traditional Chinese & Western Medicine, West China Hospital, Sichuan University for the treatment of pancreatitis in January 2018. During the treatment, the patient underwent abdominal ultrasound examination that revealed a hypoechoic nodule (2.2 × 2.1 × 1.8 cm) in the pancreatic body, dilation of the main duct (the largest diameter: 0.6 cm) in the pancreatic body and tail, and slightly hyper-echoic intrahepatic nodule (diameter: 0.7 cm) in the right liver. Subsequently, the patient was transferred to the Pancreas Surgery Department of our institution and underwent resection of masses located in the pancreatic body, surface of the liver, and diaphragm in January 31, 2018. Intraoperatively, a firm irregular mass in the pancreatic body measuring 2.5 × 2.0 × 1.5 cm, three firm irregular masses on the surface of the liver measuring 0.5–0.8 cm, and an isolated firm irregular mass located in the diaphragm measuring 1.5 × 1.0 × 0.7 cm were observed. Unfortunately, the patient again underwent cholecystectomy, choleenterostomy, and enterolysis of prior surgery due to obstructive jaundice, which is considered a complication. Pathological examination of the masses' tissues revealed carcinoma cells aggregating in papillary architecture, with folded nuclei, cells were forming nuclear grooves (). Immunohistochemical analyses showed tissue positivity for the following markers: TG, PAX-8, TTF-1, CK19, HBME-1, Galection-3, P53, WT-1, DPC4, CA19-9, and MUC1. On the contrary, the following markers were not expressed: MUC5AC, MUC6, and MUC2. Based on these findings, a diagnosis of metastatic PTCs was performed. However, the patient showed no positive symptoms and signs in the neck and head at that time. Subsequently, the patient underwent ultrasound examination and received an ultrasound-guided fine-needle aspiration (US-FNA) in the neck in February 13, 2018. Ultrasound examination showed a mass (8.1 ×5.1 ×4.1 cm) in the left lobe of the thyroid and several swollen lymph nodes in the left side of the neck, and US-FNA cytology revealed primary PTC.
An appointment was fixed with a thyroid surgeon from our institution in May 8, 2018. During the consultation, the patient presented with severe protein-energy malnutrition. After nutritional conditioning, in June 14, 2018, he was admitted to the Thyroid and Parathyroid Surgery Center for an evaluation prior to thyroid surgery. A physical examination performed in our department following postoperative recovery showed an irregular large nodule in the isthmus and left lobe of the thyroid, a swollen lymph node in the left cervical lateral compartment, and a mass in the right parotid gland. By nasopharyngeal laryngoscopy and gastroesophagoscopy, no abnormalities were observed. Ultrasound reexamination revealed the following findings: a very large hypoechoic mass (7.3 ×5.9 ×5.1 cm) in the isthmus and entire left lobe of the thyroid, multiple hypoechoic nodules (~0.2–0.3 cm) in the thyroid's right lobe, several swollen lymph nodes in the left cervical lateral compartment, several masses in the bilateral parotid region, several nodules in the bilateral salivary region, and a mass in the left gluteus maximus. US-FNA's histological results and immunohistochemical analyses confirmed the presence of metastatic PTCs bilaterally in the parotid gland, bilaterally in the salivary gland, and the left gluteus maximus. In order to further evaluate the situation and identify possible occult metastases, both an 18-fluorodeoxyglucose positron-emission tomography and computed tomography (18F-FDG-PET/CT) scan were ordered. The first revealed abnormal uptakes in the following locations: isthmus and left lobe of the thyroid, bilaterally in the parotid gland, left salivary gland, left cervical region, bilaterally in the lungs, pancreatic head, right kidney, and multiple cones, ribs, muscles and subcutaneous tissues (). The patient's serum thyroglobulin (Tg) level was 303.00 ug/L (normal range: 1.4–78 ug/L). However, the serum free triiodothyronine, free thyroxine, Tg antibody, and thyroid peroxidase antibody levels were normal.
The patient underwent palliative therapy. Specifically, on July 2, 2018, the patient received a total thyroidectomy, bilateral central neck dissection, left lateral neck dissection, and bilateral excision of both parotid glands and salivary glands. Intraoperatively, a firm irregular tumor measuring 10.0 ×7.0 ×5.0 cm was observed. The tumor mass replaced the isthmus and left lobe of the thyroid. Additionally, it extended into the tracheoesophageal region and deepened into the superior mediastinum, invading the anterior cervical skeletal muscle. Furthermore, the tumor encapsulated and infiltrated the left recurrent laryngeal nerve and slightly infiltrated the left trachea's surface. Several swollen cervical lymph nodes were identified. The largest one measured 4.0 cm. Bilaterally in the parotid and salivary regions, there were many masses ranging from 0.5 to 3.5 cm. Of note, some of the masses invaded the facial nerve. Histological examination was performed post-operatively on the paraffin-embedded specimen. Results were consistent with PTC with multiple regional lymph nodes metastases and distant parotid and salivary metastases. The patient underwent thyroid stimulating hormone (TSH) repression therapy with sodium levothyroxine (Euthyrox), administered orally. In order to prepare for the radioactive iodine (RAI) ablation therapy, oral sodium levothyroxine treatment was suspended in August 2018. After 2 weeks, RAI ablation therapy with 200 mCi of I-131 was administered. A whole-body scan (WBS) following therapeutic RAI ablation showed uptake only in the thyroid bed and no uptake in any of the metastasizing lesions. Subsequently, the patient underwent TSH repression therapy with oral sodium levothyroxine. Additionally, he was treated with lenvatinib chemotherapy from December 2018. After ~8 months of treatment, numerous metastatic lesions had lessened on computed tomography (). Additionally, serum thyroglobulin had decreased to 15.84 ug/L (from 313.60 ug/L) as of August 6, 2019. Currently, the patient is alive with no apparent symptom.
In order to complete PTC's assessment in this case, next-generation sequencing (NGS) was performed by lon PGM System with 1198X average sequencing depth. The goal was to identify gene rearrangements and genetic mutations detected in both the primary thyroid neoplasm and the metastasis in the cervical lymph node. Of note, results of our NGS demonstrated negativity for all of the following mutations: ABL1, AKT1, ALK, APC, ATM, BRAF, CBL, CDH1, CDK4, CDKN2A, CHEK2, CSF1R, CTNNB1, DNMT3A, EGFR, ERBB2, ERBB3, ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FLT3, GNA11, GNAS, HNF1A, HRAS, IDH2, JAK1, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NFE2L2, NOTCH1, NPM1, NRAS, PAX5, PDGFRA, PIK3CA, PPP2R1A, PTCH1, PTEN, RAF1, RB1, RET, SF3B1, SMAD4, SMARCB1, SMO, STAT3, STK11, TP53, U2AF1, and VHL. Only BRAF mutation was positive. Furthermore, we identified a TERT promoter mutation (C288T) by means of additional testing in the primary thyroid tumor, the pancreatic and cervical lymph node metastasis.


A 47-year-old Iranian woman of Azeri ethnicity with a history of benign breast cysts and hypothyroidism was referred to our endocrinology clinic for further evaluation of her new onset galactorrhea. She also complained of occasional headaches and nausea. She did not report any menstrual irregularities, hirsutism, visual complaints, diplopia, polyuria and polydipsia or seizures. She was a housewife with no history of occupational exposure and her familial history was unremarkable. She had never smoked tobacco or consumed alcohol. At admission, her blood pressure was 110/75 mmHg, pulse rate was 85 beats per minute, and temperature was 36.8 °C orally. A physical examination did not reveal any visual field defects and on fundoscopy both eyes were normal with sharp optic disc margins. Her visual acuity was 10/10 bilaterally. Other neurological examinations including cranial nerves were unremarkable. Her initial laboratory work-up showed a moderately elevated serum prolactin level (Table ). A hormonal assay did not show any impairments in other pituitary axes and her renal function was normal (Table ). She was not taking any medications other than levothyroxine 100 mcg daily at that time.
She underwent a dynamic 1.5 T magnetic resonance imaging (MRI) of the brain and hypophysis with images obtained every 28 seconds after injecting contrast material. The MRI showed a pituitary macroadenoma measuring 16 × 11 mm extending to the suprasellar cistern causing mild mass effect on optic chiasm (Fig. ). She was started on cabergoline 0.5 mg weekly and after 1 month her serum prolactin was lowered to 1.7 ng/mL, and her galactorrhea was resolved. Her thyroid-stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), and insulin-like growth factor 1 (IGF1) were rechecked and found to be normal again. Despite her laboratory data, our patient continued to complain of headaches and nausea. A perimetric examination did not show any significant visual field defects. A repeated MRI approximately 3 months after her initial one showed no decrease in size of the macroadenoma. She was referred to a neurosurgeon who deemed her persistent symptoms and macroadenoma reason enough for performing TSS. Prednisolone and levothyroxine were prescribed and the mass was removed and reported twice by expert pathologists as chronic granulomatous hypophysitis with negative acid-fast and periodic acid–Schiff (PAS) stains for tubercle bacilli and fungal elements. No eosinophils or features of Langerhans cell histiocytosis were reported.
Tuberculosis was ruled out in our patient by a negative tuberculin skin test, chest X-ray (CXR), and polymerase chain reaction of cerebrospinal fluid and hypophysis specimen. She did not complain of any pulmonary symptoms and a normal CXR and angiotensin-converting enzyme levels ruled out sarcoidosis as well. Serologic studies for Wegener’s granulomatosis and syphilis came back as negative. Therefore, our patient was diagnosed as having IGH. She was closely followed up postoperatively under the care of her neurosurgeon and endocrinologist with periodic office visits and laboratory tests of pituitary axes and a postoperative dynamic MRI of the sella turcica region. At 9 months of follow-up, serum levels of TSH, thyroxine (T4), gonadotropins, prolactin, cortisol, IGF1, and ACTH were normal. Moreover, her MRI did not reveal any abnormal growth or mass and she was free of headache. Fortunately, our patient’s condition was not complicated by hypopituitarism and she was symptom free 9 months after TSS.


A 47-year-old male with no past medical history presented with nausea, vomiting, diffuse abdominal pain, and a widespread rash that began 12 hours prior to arrival. Physical examination revealed an ill-appearing male with diffuse abdominal tenderness as well as diffuse purpuric, mottled skin (). Vital signs revealed a blood pressure of 93/74 millimeters of mercury, heart rate of 120 beats per minute, respiratory rate of 30 respirations per minute, and a rectal temperature of 103.7 degrees Fahrenheit with pulse oxygenation saturation of 94%. His course necessitated fluid boluses, vasopressors, broad-spectrum antibiotics, steroids, and intubation.
His laboratory findings revealed bandemia, thrombocytopenia, acute kidney injury, elevated coagulation markers, decreased fibrinogen, elevated fibrin split products, elevated lactate dehydrogenase, and a lactic acidosis as shown in the , along with an unremarkable computed tomography of his abdomen and pelvis without contrast. The presumptive diagnosis was the development of acute promyelocytic leukemia (APML) with disseminated intravascular coagulation (DIC), an uncommon skin presentation called purpura fulminans (PF), and septic shock.


An otherwise healthy 41-year-old man presented to the emergency department (ED) with a severely worsening, four-day-old diffuse, pruritic rash, which began in the inguinal regions bilaterally but had since spread to his trunk and extremities. The patient’s primary complaint was insomnia secondary to his pruritis. He initially denied any new medications or other exposures but did endorse a distant episode of contact dermatitis to poison ivy two years prior. On arrival, his vitals included temperature of 98.3º Fahrenheit, blood pressure of 133/87 millimeters of mercury, heart rate of 69 beats per minute, respirations of 18 per minute, and a pulse oximetry of 100% on room air.
The patient’s physical exam was remarkable for a macular, blanching, non-vesicular, erythematous rash on all extremities, chest, and back, sparing the palms, soles, and oral mucosa. Lungs were clear to auscultation in all fields. Further diet history detailed consumption of two mangos two days prior to the onset of the rash. The patient’s wife, who accompanied him to the ED, had also consumed mangos two days prior but was asymptomatic. Although both the patient and his wife handled the mango peels, the wife did not endorse prior plant exposures resulting in rash.
Given the patient’s substantial discomfort, intravenous (IV) access was established, and 50 milligrams (mg) of diphenhydramine and 50 mg ranitidine were parenterally administered. This resulted in significant relief of pruritus and mild improvement in visible rash. After a brief observation period, the patient was discharged home on 60 mg of oral prednisone for five days and 20 mg of oral loratadine, as needed. Of note, the patient deferred the first steroid dose in the ED due to the evening time of presentation and a remote history of insomnia after taking steroids. He was contacted five days after his ED visit with almost complete resolution of symptoms and significant improvement in insomnia with over-the-counter (OTC) oral diphenhydramine. Extending steroid treatment for an additional week was discussed, but the patient declined based on the improvement of his symptoms. He was contacted again approximately three months after his ED visit and denied any rebound symptoms.


A 47-year-old man was hospitalized because of jaundice and rashes. He developed jaundice 2 weeks prior to admission. He had no fever, fatigue, anorexia, abdominal pain, or waist pain. The laboratory examinations in local hospital revealed an alanine aminotransferase (ALT) of 359 U/L, an aspartate aminotransferase (AST) of 161 U/L, an alkaline phosphatase (ALP) of 580 U/L, a gamma-glutamyl transpeptidase (GGT) of 883 U/L and a total bilirubin (TBIL) of 75.1 umol/L. He received a liver protective medication (diammonium glycyrrhizinate), but jaundice did not improve. On the third day of diammonium glycyrrhizinate treatment, multiple non-itchy rashes appeared all over his body, which remained after the withdrawal of diammonium glycyrrhizinate and the application of anti-allergic agents. In addition, his ALP and GGT increased to 853 and 1012 U/L in the fifth day. He was then transferred to our hospital. He denied any chronic diseases, drug administration, alcohol consumption or venereal exposure. Physical examination showed the temperature of 36.0 °C, the blood pressure of 108/75 mmHg, the heart rate of 77 times/min and the breath rate of 18 times/min. His skin and sclera were mildly yellowish. No hepatomegaly, splenomegaly or ascites was found. Non-itchy macular rashes measuring 0.5 to 2 cm were observed all over his body, including some on the soles and palms (Fig. a and b). No genital or buccal lesions were found. Biochemical examinations in our hospital revealed a weakly positive in hepatitis B surface antigen (HBsAg). His hepatitis B surface antibody, hepatitis B extracellular antigen (HBeAg) were both negative and his hepatitis B virus DNA was undetectable (< 500 IU/ml). The other laboratory tests including Hepatitis A virus, Hepatitis C virus, Hepatitis E virus, human immunodeficiency virus, Epstein-Barr virus, cytomegalovirus, and other autoantibodies were all negative. Abdominal ultrasonography and magnetic resonance cholangiopancreatography revealed the normal biliary tract, liver, and spleen. He underwent liver biopsy and the results revealed granulomatous hepatitis with stage 2 inflammation and stage 1 fibrosis (Fig. c, d, e, and f). Mild hepatic lobule inflammation and plasma cells infiltrating were found in the portal area. In addition, micro-granulomas with coagulation necrosis were noticed in the portal area. Immunohistochemistry examination showed a weakly staining of HBsAg and HBcAg. He received a following test of syphilis. The rapid plasma reagin test (RPR) was positive (1,32 titer), and the Treponema pallidum particle assay (TPPA) test was 1:38, which confirmed the diagnosis of syphilis. The patient was then given intramuscular benzathine penicillin treatment at a dose of 2.4 million units per week for successive 2 months. No anti-HBV drug was given. The liver enzymes decreased rapidly after penicillin treatment and finally returned to normal level after 2 months of treatment. The follow-up showed that the liver function kept normal and HBV DNA was still undetected after 1-year.


A 16-year-old male patient came to the emergency department of Civil Hospital Karachi with a complaint of high-grade fever for 14 days, headache and neck pain for 12 days, vomiting for 10 days, and altered level of consciousness since one day. According to the patients' attendant, he was in his usual state of health 14 days ago, when he developed a high-grade fever that was sudden in onset, associated with rigors and chills, and didn't follow a certain pattern. However, it was partially relieved by taking medicine from a nearby clinic. The patient also complained of neck stiffness and pain for the past 12 days along with the fever and eight to nine episodes of vomiting per day for 10 days, which usually contained food particles and was non-projectile, without any odor or blood and approximately a glass full. Since the last one day, the patient also developed an altered level of consciousness gradually. There was also a history of an episode of a fit a day before. He gave a history of headache, neck pain, hemoptysis, and shortness of breath the same day. One of his close family members had tuberculosis (TB).
On examination, he had blood pressure (BP) of 130/80 mm of Hg, pulse rate of 102 beats/minute, a temperature of 100ºF, and a respiratory rate of 16 breaths/minute. His neck stiffness came out to be positive while Kernig's sign was also positive. The patient was irritable, didn't respond well, and was not well-oriented. His plantars were bilaterally downgoing.
The plan was to do magnetic resonance imaging (MRI), 24 hourly urinary protein, lumbar puncture, and random blood sugar every four hours. His WBC count was 5500 mm3, hemoglobin concentration was 9.3 g/dl, and platelet count was 185,000 mm3. His C-reactive protein level was 14.6 mg/dl. Urine D/R showed protein 2++, glucose 2++, ketone bodies 2++, blood 2++, and RBCs about 20-25 cells. CSF fluid examination revealed numerous pus cells. The result for gram-negative rods came negative with Indian ink. The culture had moderate growth of Salmonella typhi that was resistant to all drugs but was susceptible to meropenem, azithromycin, and imipenem and thus showed extended drug resistance.
He was shifted to the surgical ICU (Figure ), where they reported that a neck swelling had developed and the patient presented with stridor, shortness of breath, tachypnea, tachycardia, and O2 saturation of 60%.
Immediate tracheostomy and intubation were performed and the ear, nose, throat (ENT) surgeon was also called. The plan was to give meropenem and clindamycin as gram-negatives. As metronidazole has better anaerobic coverage and is less resistant then clindamycin, metronidazole was given instead. The ENT specialist assessed the patient and noted him to be dyspneic, using accessory muscles for breathing, coarse crepitus bilaterally, harsh vesicular breathing, and an upper airway obstructed lesion. The chest X-ray showed pleural effusion bilaterally (Figure ).
A chest tube was placed due to subcutaneous emphysema. The computed tomography (CT) scan showed dilated ventricles and mild cerebral edema. Symptoms improved with antibiotic use. The patients' health slowly progressed, his appetite and sleep were normal. Blood and stool cultures were found to be negative. He was admitted for the following 10 days and then later discharged when he was afebrile and feeling well. Meropenem was continued for a week, and the patient was advised to consult neurological therapy to reach neurodevelopmental goals.


A 36-year-old female had a progressive headache. The patient was diagnosed with CVST by MRV and treated with anticoagulant therapy with no response to systemic heparinization. DSA revealed thrombosis in the SSS, SS, and TS (). Lumbar puncture showed intracranial pressure >600 mmH2O. On the second day after admission, intrasinus thrombolysis was performed (). During thrombolysis, the patient's symptoms gradually got worse and lost vision gradually. Cerebrospinal fluid cytology revealed a large number of abnormal cells, and considered malignant tumors (). On the 8th day after thrombolysis, the patient had sudden consciousness disturbance and died in emergency.


A 35-year-old pregnant woman presented with headache and nausea for 4 days, physical convulsions, and low right limb muscle strength (I–II). MRV showed CVST and the intracranial pressure was 300 mmH2O (). DSA showed no recanalization of the SSS and SS before treatment (), and microcatheter was placed in the SSS (). On the 5th day of thrombolysis, the symptoms of the patients completely resolved. MRV showed the SSS and SS were recanalized at discharge (). MRV showed venous sinus were unobstructed and there was no significant recurrence at 6-month follow-up ().


A 66-year-old Arab woman with diabetes mellitus of 4 years’ duration underwent transsphenoidal (TSS) resection of a nonfunctioning pituitary macroadenoma in May 2018. Her immediate postoperative course was free of events. Three months after the procedure (August 2018), she checked in to our institution with chronic headaches. Her physical examination showed bitemporal hemianopia. Relevant blood screening results were as follows: thyroid stimulating hormone ultra sensible (TSHus), 0.3 mIU/L (normal range, 0.5–5); free thyroxine (FT4), 0.7 ng/dl (1–2); adrenocorticotropic hormone (ACTH) (8:00 a.m.), 3 pg/ml (10–40); cortisol (8:00 a.m.), 6 μg/dl (10–20); follicle stimulating hormone (FSH), 20 IU/L (30–110 postmenopausal); luteinizing hormone (LH), 10 IU/L (15–54 postmenopausal); estradiol, 1.2 pg/ml (< 10 postmenopausal); growth hormone (GH), 2 ng/ml (< 10 [women]); prolactin, 0.7 ng/ml (2–20 [nonpregnant]); C-reactive protein (CRP), 2 mg/L (< 3.0); and white blood cells (WBC), 10.5 × 109/L (4.0–11.0 × 109/L).
Brain MRI showed a pituitary mass measuring 4 cm of the major axis, exhibiting low T1-weighted (T1w) signal, high T2-weighted (T2w) signal, and diffusion-weighted imaging (DWI) with rim enhancement after injection of gadolinium. The mass was responsible for a compression of the optical chiasma (Fig. ).
After hormone substitution therapy, endoscopic endonasal drainage via TSS route was performed, which brought back a purulent fluid with no macroscopic tissue fragments inside. Following the drainage and irrigation of the PA, the result of a close exploration was negative for tumoral lesion. No intraoperative cerebrospinal fluid (CSF) leak in conjunction with a valsalva maneuver. Closure was achieved with Gelfoam packing (Pharmacia and Upjohn, Kalamazoo, MI, USA) and Surgicel overlay (Ethicon, Somerville, NJ, USA). The purulent material grew a Streptococcus epidermidis, and histopathological examination showed no tumoral lesion. On the basis of the antibiotic sensitivity test, targeted antibiotherapy was administered for 3 weeks. The postoperative course was uneventful, with progressive improvement of the clinical state. Follow-up MRI at 3 months showed a very sizable reduction of the PA (Fig. ).


A 64-year-old Arab man with no major medical history consulted in December 2017 for chronic headaches and progressive vision loss, evolving for 1 year, with neither fever nor asthenia. His physical examination was remarkable only for a chiasmal syndrome. He did not have diabetes insipidus. Relevant blood screening results were as follows: TSHus, 0.25 (0.5–5); FT4, 0.7 ng/dl (1–2); ACTH (8:00 a.m.), 5 pg/ml (10–40); cortisol, 3 μg/dl (10–20); FSH, 0.7 IU/L (–); LH, 0.5 IU/L (0.7–7.9 [ages 20–70 years]); testosterone, 50 ng/dl (200–900 [male age > 19]); GH, 1.5 ng/ml (< 5 [men]); CRP, 3 mg/L (< 3.0); and WBC, 9.7 × 109/L (4.0–11.0 × 109/L).
Brain MRI showed a 3-cm pituitary mass with a cystic and hemorrhagic component; it was heterogeneous with mixed high and low T1w and T2w signaling, and it exhibited rim enhancement. DWI showed mild and partial high intensity in the central part of the mass (Fig. ).
At this stage, the two relevant differential diagnoses were pituitary adenoma (with necrosis and cyst degeneration) and PA. These MRI findings were mostly in favor of a remodeled pituitary mass. That is what was shown on the final MRI report.
After hormone substitution therapy, patient 2 underwent TSS surgery with intraoperative discovery of a PA that was drained. No macroscopic tissue fragments were found inside the purulent matter. Following drainage and irrigation of the PA, the result of a close exploration was negative for tumoral lesion. There was no intraoperative CSF leak in conjunction with a valsalva maneuver. Closure was achieved with Gelfoam packing and Surgicel overlay. The purulent material grew Staphylococcus aureus, and histopathological examination showed no tumoral lesion. On the basis of an antibiotic sensitivity test, targeted antibiotherapy was administered for 3 weeks. The postoperative course was uneventful, with progressive improvement of the clinical state. Follow-up MRI at 3 months showed complete drainage of the abscess (Fig. ).


A 69-year-old male with a medical history of T2DM and stage IV NSCLC presented to our ED with complaints of nausea, vomiting, polyuria, polydipsia, and weakness of 4 days duration. His T2DM was diagnosed 4 years prior to his presentation and had been managed with oral antidiabetic drugs (OADs); his glycohemoglobin levels ranged between 5.9 and 7.3%. He had been undergoing chemotherapy with carboplatin, pemetrexed, and pembrolizumab and had completed his 4th cycle 20 days prior to this presentation.
On physical examination, he had dry oral mucosa and was tachypneic with a respiratory rate of 30 respirations per minute. Laboratory workup revealed a pH of 6.95, a serum bicarbonate level of 3 mmol/L with an anion gap of 39 mmol/L. Serum osmolality was elevated at 342 mOsm/kg. Blood glucose was 907 mg/dL, and serum ketones were 5.3 mmol/L. His serum potassium level was 7.5 mmol/L, and his serum creatinine level was elevated to 2.72 mg/dL from a normal baseline. Glycohemoglobin was 9.2%. The patient was admitted to the intensive care unit (ICU), where he was started on an intravenous (IV) insulin infusion and IV fluids with serial monitoring of his blood glucose, pH, and potassium levels. His DKA resolved and he was started on long-acting and short-acting insulin.
Workup for potential precipitating events leading to DKA was done. After exclusion of infectious and common metabolic etiologies, it was thought that the patient's treatment with pembrolizumab may have led to new-onset ICPI-induced T1DM presenting with DKA. Subsequently, C-peptide levels were checked and were undetectable (<0.1 mg/mL). Anti-glutamic acid decarboxylase antibody (Anti-GAD) titers were elevated at 61 U/mL, both of which were consistent with a diagnosis of T1DM. His pembrolizumab was held for one cycle and resumed thereafter.
Following his discharge from the hospital, the patient was maintained on a regimen of long- and short-acting insulin with insulin degludec and insulin aspart. However, it became challenging to achieve adequate glycemic control despite the patient's compliance with insulin therapy. His glycohemoglobin was persistently high and was 8.7% after being on insulin for 15 months. His insulin regimen was subsequently supplemented with metformin, which led to a decrease in his glycohemoglobin from 8.7% to 7.7% one month after the change in regimen. He remains on maintenance therapy with pembrolizumab for his NSCLC and has not had further ICPI-associated complications on his last follow-up.


A 70-year-old man with bladder cancer underwent an endoscopic bladder tumour resection. Prior to him undergoing this surgery, a full body scan was performed, in which a lung tumour in his left upper lobe was identified. He was diagnosed with metastatic lung cancer and was admitted to our institution for the resection. Video-assisted thoracoscopic surgery was undertaken to perform the left upper lobectomy. The patient's chest tube was removed on post-operative day 3 without any complications. On post-operative day 6, the patient developed dyspnoea, and a chest X-ray image showed his left lung had collapsed because of post-operative pneumothorax. Chest tube drainage was commenced, and by post-operative day 19, he developed left empyema due to pneumonia in the residual left lung. With antibiotic therapy, the patient's inflammatory markers improved. However, on post-operative day 42, massive air leakage was identified. The chest computed tomography (CT) scan showed damage to the lung tissue in the superior segment of the left lower lobe and several bronchi leading to the intrathoracic cavity (Fig. A,B,C). We diagnosed post-operative peripheral BPF. The left bronchi, B6a, B6b, and B6c, were identified using a three-dimensional CT as the target bronchi for BPF. Bronchial occlusion with EWS (Novatech, Cedex, France) was performed immediately under local anaesthesia. A flexible bronchoscope, BF-P-290 (Olympus, Tokyo, Japan), and V-shaped grasping forceps were used for the deployment of the EWSs. A digital drainage system (Thopaz, Medela, Baar, Switzerland) was used to confirm the effectiveness of the bronchial occlusion. EWSs were occluded in the left B6a, B6b, and B6c bronchi (Fig. D), and reduction in air leakage was achieved through the procedure (Fig. ). The chest tube was removed one week after the bronchial occlusion when the air leakage had completely stopped. The patient did not want a repeat bronchoscopy, so he was examined subsequently in a six month clinical and CT imaging follow-up and appeared to be in a good condition with no signs of BPF. We have no intention of removing deployed EWS unless the patient has complications such as pneumonia and lung abscess arising from EWS. Chest CT findings after six months showed no evidence of infection. If air leakage after removal reappears, we propose to use a combination of occlusion with re-placement of EWS plus additional pleurodesis.


A previously healthy 10-year-old boy was admitted to our hospital because of a fever. The physical examination showed petechial hemorrhage of the precordia and leg, but it did not indicate hepatosplenomegaly or lymphadenopathy. Results of the laboratory examination indicated leucocytosis, anemia, and thrombocytopenia. The following findings were observed: white blood cell count, 127,000/µL; neutrophil count, 2.0%; blast cell count, 94.5%; hemoglobin level, 9.3 g/dL; and platelet count, 1.7 × 104/µL. Lactate dehydrogenase and transaminase levels were 2371 IU/L and within normal range, respectively. The bone marrow (BM) examination revealed hypercellular BM. The nucleated cell count was 26.4 × 104/μL with a blast cell count of 71.8% (Figure A,B). The result of the peroxidase staining was negative, that of α-naphthyl butyrate esterase staining was positive, that of naphthol AS-D chloroacetate esterase staining was negative, and that of sodium fluoride staining was positive. As examined by flow cytometry, the immunophenotype of the blast cells showed positivity for cytoplasmic-myeloperoxidase (42.9%), CD11b (75.1%), CD13 (95.9%), CD33 (99.2%), CD34 (98.0%), CD38 (35.9%), CD56 (96.2%), CD58 (70.6%), CD64 (43.1%), CD99 (93.4%), and CD117 (86.8%). Chromosomal banding of BM cells revealed 46,XY,del(6)(q21),t(16;21)(p11.2;q22),der(17)t(1;17)(q12;q25)[20]. The patient was negative for FLT3-ITD, and the quantitative determination of FUS-ERG-messenger RNA (mRNA) in BM was 1,608,400 copies/μg RNA. The diagnosis of AML with t(16;21)(p11;q22)/FUS-ERG and M5a according to the French-American-British classification was made based on the BM examination.
According to the AML-05 protocol of the JPLSG, two courses of induction chemotherapy were administered, but CR was not achieved. The chemotherapy (granulocyte colony-stimulating factor 5 μg/kg/d on days 1-6, idarubicin 10 mg/m2/d on days 2-4, fludarabine 30 mg/m2/d on days 2-6, cytarabine 2 g/m2/d on days 2-6) that included gemtuzumab ozogamicin (3 mg/m2/d on day 7) led to CR, which was followed by peripheral blood stem cell transplantation (PBSCT) from a human leukocyte antigen (HLA)-matched sibling donor at 11 years of age. Sibling donor was sister. The conditioning regimen consisted of melphalan (L-PAM) (90 mg/m2/d daily for 2 days) and buslfan (4 mg/kg/d daily for 4 days). Graft-versus-host disease (GVHD) prophylaxis was performed with short-course methotrexate (MTX) and cyclosporine. BM engraftment was achieved 12 days after PBSCT, but veno-occlusive disease (VOD) and infective endocarditis developed 20 and 68 days after PBSCT, respectively. Although GVHD prophylaxis had been discontinued because of VOD, he did not have acute GVHD.
At 145 days, the BM examination revealed the presence of blast cells (3%), 46,XY,del(6)(q21),t(16;21)(p11.2;q22),der(17)t(1;17)(q12;q25)[1]/46,XX[19] in the chromosome banding, and an increased expression of WT1-mRNA (8,000 copies/μg RNA). He was diagnosed as having a cytogenetic relapse after PBSCT. At 156 days, AZA was administered (100 mg/m2/d for 5 days, every 28 days). After two courses of AZA were administered, CR was achieved a second time and chromosomal banding of BM cells revealed 46,XX[16]. The quantitative determination of WT1-mRNA in peripheral blood was significantly reduced to 140 copies/μg RNA after three courses of AZA. For approximately 8 months, eight courses of AZA were administered, but he was diagnosed as having relapse in the BM and central nervous system (CNS) a second time. The hematotoxicity of AZA was neutropenia of Grades III-IV and febrile neutropenia.
Although low-dose Ara-C and aclarubicin with concomitant use of a granulocyte colony-stimulating factor regimen and triple intrathecal therapy (TIT) consisted of cytarabine (30 mg), methotrexate (12 mg), and hydrocortisone (25 mg) were administered, a third CR was not achieved. TIT was performed a total of 7×, and cerebrospinal fluid test revealed that the leukemia cells were negative. He underwent cranial irradiation (14 Gy) and subsequently received a reduced-intensity conditioning regimen consisting of fludarabine (30 mg/m2/d for 4 days), cytarabine (2 g/m2/d for 4 days), L-PAM (60 mg/m2/d for 3 days), and low-dose total body irradiation (4 Gy) with HLA-matched cord blood transplantation (CBT). GVHD prophylaxis was performed with short-course methotrexate (MTX) and tacrolimus. Thrombotic microangiopathy developed 9 days after CBT, and primary graft failure (GF) was diagnosed 20 days after CBT. Therefore, he underwent PBSCT with an HLA-matched sibling donor without conditioning regimen 20 days after CBT because of GF.
Although BM engraftment was achieved, he died of septic shock due to Klebsiella pneumoniae at approximately 3 months after CBT. According to the autopsy results, the presence of leukemic cells was not confirmed.


An 18-month-old boy with a healthy clinical history presented with left-sided status of clonic convulsion lasting over 30 min following fever. Enterovirus was isolated from his pharyngeal secretion on the day of admission. Three days following onset, brain DWI showed reduced diffusivity on subcortical white matter in the right hemisphere. He was diagnosed with viral infection associated-acute encephalopathy and treated with methylprednisolone pulse therapy, high dose immunoglobulin and continuous intravenous midazolam. After the acute phase of the encephalopathy, he presented with left hemiparesis. Left side dominant-tonic spasms recurred 3 months following onset. Despite treatment with clobazam, lamotrigine, topiramate, carbamazepine, and levetiracetam, the seizures continued to occur daily.
He was referred to our epilepsy center at the age of 39 months. He had left hemiparesis and could only speak a few words. His developmental quotient (DQ) was 46 on the Kinder Infant Development Scale. Long-term video-electroencephalogram (EEG) monitoring revealed that the left side dominant-tonic spasms (10/day) coincided with ictal changes of diffuse spike bursts followed by biphasic or triphasic diffuse slow waves, and that the myoclonic seizures (>30/day) coincided with diffuse polyspikes and waves. Brain MRI revealed right cerebral atrophy and hypoperfusion with arterial spin labeling (ASL). At the age of 41 months, he underwent right hemispherotomy. He was free from any seizures up to the last follow-up at 10 months after the surgery. The left hemiparesis transiently worsened after the surgery and then recovered to the presurgical level. His attention and cognitive function improved.
The histopathological examination with hematoxylin-eosin staining revealed an excessive number of neurons and glial cells in the white matter with intact cortical architecture and absence of aberrant cells, corresponding to FCD type IIId, on the right tip of the temporal lobe (, ). No changes were observed in the right amygdala and hippocampus.


A 28-month-old boy with a healthy clinical history presented with left-sided status of clonic convulsions lasting >30 min with fever. His pharynx was positive for the antigen of influenza virus type A. Brain DWI showed reduced diffusivity in the cortex and subcortical white matter in the right hemisphere, at 5 days after the occurrence (). He was treated with methylprednisolone pulse therapy and high dose immunoglobulin, mannitol, phenobarbital, and continuous intravenous midazolam. After encephalopathy onset, he presented with left hemiparesis, and suffered from left side dominant- or symmetrical tonic spasms. Although he was treated with phenobarbital, valproic acid, clobazam, perampanel, lamotrigine, and levetiracetam, seizures continued to occur daily.
He was referred to our epilepsy center at the age of 56 months. DQ was 31 on the Kyoto Scale of Psychological Development and he presented with left hemiparesis. Long-term video-EEG revealed left side dominant-tonic spasms and ictal attenuation in the right hemisphere with a frequency of 2–5/day. Brain MRI revealed right hemispheric atrophy and right hemispheric hypoperfusion with ASL (). At the age of 59 months, he underwent right hemispherotomy. He was free from any seizures up to 11 months after the surgery. The left hemiparesis worsened transiently after the surgery and then recovered to the presurgical level.
The histopathological examination with hematoxylin-eosin staining revealed an excessive number of neurons and glia cells in the white matter with intact cortical architecture and absence of aberrant cells, corresponding to FCD type IIId, in the cerebral tissues of the tip of the right temporal lobe () and adjacent to the right hippocampus. No changes were observed in the right amygdala and hippocampus.


A 17-month-old boy with a healthy clinical history presented with left-sided status of clonic convulsion lasting 60 min. Human herpesvirus 6 was isolated from his pharynx. He was treated with methylprednisolone pulse therapy and continuous intravenous midazolam. Three days following onset, cortical-subcortical restricted diffusivity was observed on the left temporo-parieto-occipital lobes in brain DWI. Following the acute phase, he continuously developed focal seizures accompanied by impaired consciousness and cyanosis. Despite treatment with valproic acid, clobazam, lamotrigine, perampanel, topiramate, and levetiracetam, daily focal seizures accompanied by mouthing, grimacing or expressions of fear continued to occur. Two months following onset, brain MRI revealed left hemispheric atrophy.
He was referred to our epilepsy center at the age of 56 months. He was not paralyzed but was barely able to speak. DQ was 34 on the Kyoto Scale of Psychological Development. Long-term video-EEG monitoring revealed that the focal impaired awareness seizures coincided with ictal EEG activities from the left frontal and occipital areas, which sometimes evolved into asymmetrical tonic seizures (extensions of left extremities and flexion of right extremities). Left hemispheric atrophy was observed in brain MRI. At the age of 60 months, he underwent left subtotal hemispherotomy (hemispherotomy sparing the pyramidal tract). He was free from seizures up to the last follow-up 10 months after surgery.
The histopathological examination with hematoxylin-eosin staining revealed immature-like neurons with large nuclei in the cerebral cortex of the tip of the left temporal lobe (). An excessive number of neurons and glial cells was observed in the white matter of the same region, corresponding to FCD type IIId (). Clustering of immature-like neurons was observed in the left amygdala () and gliosis was observed in the right hippocampus.


A 33-year old man attended our hospital with a sacral mass (80 mm × 59 mm × 53 mm) detected by magnetic resonance imaging (MRI) two days previously. The patient defecated once every 4 to 5 days. The patient had no nausea or vomiting, no abdominal pain or distention, no blood in stools, and no rectal tenesmus. The patient attended our hospital for surgical treatment. During the course of the disease, the general condition, diet, and mental state of the patient were good. There was no history of cough, urinary frequency and urgency, or any other abnormal sensations. Based on the digital rectal examination (knee-chest posture), the mass was palpable within 4 cm at the 12 o’clock position. The mass was solid with a clear boundary, good mobility, and no tenderness. However, the upper edge of the mass could not be felt. In addition, there was no blood or pus staining on the surface of the glove. The MRI examination showed numerous short T1 signals and long T2 signals and many long T1 signals and mixed T2 signals in the posterior rectal space (Fig. ). The largest mass was approximately 100 mm × 59 mm × 53 mm in size and compressed the rectum and bladder filling was poor. There were no abnormalities in the size of the prostate and bilateral seminal vesicles. There were no enlarged lymph nodes in the bilateral para-femoral and inguinal regions. The MRI examination indicated abnormal signals in the retrorectal and anterior sacral spaces, and the cystic masses were investigated more fully. The carcino-embryonic antigen (CEA) level was 26.97 ng/mL (normal: 0–3 ng/mL) and the carbohydrate antigen 19–9 (CA 19–9) level was 106.50 U/mL (normal: 0–35 ng/mL). However, gastroscopic and enteroscopic examinations showed no signs of gastrointestinal tumor.
The patient underwent surgical resection of the masses located in retrorectal and anterior sacral spaces. Lumbar anesthesia was performed with the patient in the left lateral position. An incision of approximately 10 cm was posterior sagittal and located 1 cm to the right of midline. The coccyx tip was removed to expose the presacral mass. During the surgical procedure, a cystic mass was found in the right and posterior lateral region of the rectum and 200 mL pale yellow liquid was drained. The cystic mass was carefully separated and resected. Another mass was observed adjacent to the cystic mass and light green viscous liquid was drained. The mass was also separated and resected (Fig. ). Complete masses resection with adequate margin was performed to achieve the R0 resection. The resected tissues were sent for further histopathological examination. A drainage tube was placed in the retrorectal and anterior sacral spaces. The operation was performed without problems, and the patient was given oxygen, anti-inflammatories, and fluid replacement treatment.
The histopathological examination revealed that the masses were tailgut cysts accompanied by carcinogenesis (high to moderately differentiated adenocarcinoma) infiltrating the smooth muscle wall and surrounding fibrous tissues (Fig. ). The immunohistological examination showed positive staining of CDX2, CK20, Ki67, and villin, which further indicated the adenocarcinoma transition of the tailgut cysts (Fig. ). The CEA level was 2.82 ng/mL (normal: 0–3 ng/mL) and the CA 19–9 level was 30.52 U/mL (normal: 0–35 ng/mL) 1 week post-surgery. The patient recovered well and was discharged 10 days post-surgery.


A 14-year-old Syrian girl with Thalassemia Major presented to the emergency room
with a three-month history of increasing fatigue, dyspnea, and abdominal
distension. Her medical history revealed that she had been diagnosed with
Thalassemia Major at the age of one year old, and she received irregular
erythrocyte transfusion and iron chelation therapy in her country. It was
learned that the compliance for previous blood transfusion and chelation therapy
was very poor. On general examination, she was undernourished with short stature
(body weight < 25 p, height < 3p) and the physical examination revealed
dyspnea with a typical facial thalassemic feature without cyanosis.
Chest x-ray showed areas of consolidation on both sides of the lungs and
increased cardiothoracic ratio ().
The electrocardiogram showed sinus rhythm with 70/min heart rate and
prolongation of QTc value with 0.46 seconds (). Transthoracic echocardiography revealed both ventricle
systolic and diastolic ventricular dysfunction, left ventricle ejection fraction
was 48% and fractional shortening was 24% were calculated with a mild left
ventricle dilatation ().
Mild-moderate mitral regurgitation and trivial pericardial effusion were also
observed. Right ventricular inflow view in systole showing thickened, immobile
leaflets of tricuspid valve in a fixed open position, causing mal-coaptation and
severe regurgitation without stenosis (see and ). Apical
four-chamber view in diastole showed immobile leaflets of tricuspid valve in a
fixed open position, as showed by the color Doppler () (See additional files , and ). Right atrial, right ventricle dilatation
and minimal pulmonary regurgitation with mild pulmonary hypertension were also
observed.
After hospitalization in the intensive care unit, inotropes, diuretics and iron
chelation treatment (Dopamine, Dobutamine, Furosemide infusion, Propranolol,
Enalapril, Aldactone and Deferoxamine, Deferiprone therapy) started as soon as
possible. Cardiac enzymes were sent to screen possible myocarditis, and D-dimer
was sent to detect pulmonary thromboembolism. Results were found to be negative.
On the seventh day of hospitalization, the electrocardiogram showed atrial
flutter (). Therefore, digoxin
and low molecular weight heparin treatment were also started. In the second
week, the patient developed acute renal insufficiency and the electrocardiogram
showed atrioventricular dissociation and ventricular extra-systole (). Immediately after the digoxin
treatment had been stopped, amiodarone infusion has started. Holter
monitorization revealed atrioventricular dissociation and non-sustained
ventricular tachycardia (). Blood
level of Digoxin was within normal reference values. Serial echocardiography was
performed and no difference has been observed in the cardiac parameters during
the hospitalization. Despite atrioventricular dissociation, we decided to
follow-up her without pacemaker implantation due to hemodynamic stability.
Although secondary prevention of implantable cardioverter defibrillator was
decided after the patient was taken to control ventricular arrhythmias with
amiodarone, she died due to ventricular tachycardia on the 22nd day of
hospitalization.


A 3-month-old girl with correctable biliary atresia with a cystic structure at the porta hepatis (Icyst-c1-α according to the Japanese Biliary Atresia Society Classification []) underwent cystoduodenostomy in the Tohoku University Hospital (Fig. ). The jaundice she had experienced during the preoperative period disappeared following the surgery. She did not have health issues during childhood. At 15 years of age, she developed adhesion ileus and was admitted to a different hospital. In the following year, she underwent multiple surgeries including lysis of intestinal adhesion, ileostomy, closure of ileostomy, and gastrojejunostomy with Braun anastomosis in the same hospital. Diaphragmatic eventration was identified on her chest X-ray obtained in the hospital when she was aged 17 years.
At 31 years of age, she was referred to the Tohoku University Hospital because of poor general condition with ileus. Laboratory studies showed severe jaundice and malnutrition with total bilirubin level, 16.7 mg/dl; direct bilirubin level, 11.2 mg/dl; albumin level, 2.5 g/dl; and zinc level, 23 μg/dl. She developed generalized severe dermatitis due to zinc deficiency. She was diagnosed with volvulus affecting the jejunal loop where she underwent gastrojejunostomy; she subsequently developed blind loop syndrome. The dilated jejunal loop chronically pushed the left diaphragm upward, resulting in diaphragmatic eventration. The dilated jejunum was resected, and the gastrojejunostomy was restored in a Roux-en-Y fashion. Diaphragmatic plication was also performed (Fig. a). Thereafter, she was followed up in our department.
She had a habit of smoking 10 cigarettes/day for 34 years until 54 years of age, and then she quit smoking. She also had a habit of consuming a daily nightcap with small amount of alcohol. At 54 years of age, she developed cholangitis associated with gallstones at the porta hepatis (Fig. b), which were eventually removed. Following this, the residual cystic bile duct and gallbladder were resected, and biliary reconstruction was performed by hepaticojejunostomy in a Roux-en-Y fashion (Fig. c). No pathologically malignant or dysplastic changes were found in the resected specimens of the bile duct and gallbladder. We continued to follow up with the patient on a regular basis.
At a follow-up assessment when the patient was approaching the age of 63, her liver function test results were within the normal range (Table ). Computed tomography (CT) scan showed neither gallstones nor tumors in the liver (Fig. a).
However, at 8 months later, her liver function test results showed slight abnormalities (Table ). Among tumor markers assessed at that time, carcinoembryonic antigen and cancer antigen 19-9 levels were elevated; both markers were within normal range 10 months before (Table ). Ultrasonography showed dilated intrahepatic bile ducts, and a liver tumor at the porta hepatis was found by CT (Fig. b). Pathological specimens obtained by endoscopic tumor biopsy showed adenocarcinoma (Fig. a, b). She was diagnosed with cholangiocarcinoma that was already progressive and unresectable. Although she underwent cancer chemotherapy with gemcitabine, the tumor rapidly progressed. She died just before the age of 64 years. The postmortem autopsy was not performed, according to the will of her family.


In July 2018, a 63-year-old male patient received an emergency referral to our department from his primary care physician; on the previous day, the patient had noticed a feeling of numbness of the left lower lip and chin while eating his breakfast. The patient compared the sensation to that after being given anesthetic by the dentist. He reported that when getting up that morning, he had already experienced a feeling of uncertainty and a slightly unsteady gait, but that these had completely cleared after a short time. The patient’s medical history revealed Lyme disease with Bannwarth syndrome in 2017, a pulmonary embolism in 2017, a right vestibular neuropathy in 1998, arterial hypertension, nicotine consumption of 80 pack years, as well as a tonsillectomy in 1982. With regard to medications, the patient took 2.5 mg/d of ramipril for the treatment of arterial hypertension. The neurological examination revealed an approximately 2 × 3 cm area of hypoesthesia in the area of the chin and left lower lip. The patient’s sense of taste and smell were intact and the nerve exits were not painful on palpation. Otherwise, the cranial nerve status presented as normal and the muscles were normal in tone and eutrophic without paresis. The muscle reflexes were symmetrical and in the lower half of the normal range. The sensitivity to touch was normal, and coordination was intact. The cranial MRI revealed an acute ischemia in the right thalamus. Over the further course of the inpatient stay, further cerebro- and cardiovascular diagnostics were conducted with Duplex sonography of the brain-supplying arteries, long-term ECG and blood pressure monitoring, laboratory diagnostics, and transesophageal echocardiography. These revealed an increased risk of arteriosclerosis without indications of an embolic etiology of the ischemia. The patient was put on 100 mg of acetylsalicylic acid for cerebrovascular secondary prevention, a cholesterol-lowering treatment with 20 mg of simvastatin was initiated, and the patient was urgently advised to refrain from further nicotine consumption.


Our patient was an 11-year-old Japanese boy (height 141 cm, weight 36.5 kg) with acute lymphocytic leukemia. Since the onset of acute lymphocytic leukemia, he had received early-stage intensive chemotherapy, remission therapy, and maintenance therapy; however, because he had a positive test result for minor breakpoint cluster region, umbilical cord blood transplantation was performed. After transplantation, he complained of abdominal and articular pain; his abdominal pain was accompanied by frequent diarrhea. These were considered to represent gastrointestinal symptoms of graft-versus-host disease (GVHD); thus, opioid therapy was initiated. For long-term opioid therapy, few opioid medications provide information on the label regarding the safety and effectiveness of the drug in pediatric patients []. We selected fentanyl because chemotherapy for leukemia predisposes the patient to renal dysfunction, and it is considered effective because it has high selectivity for mu 1 receptors in the treatment of mucosal pain [, ]. However, the dose of fentanyl was gradually increased for pain management, resulting in dose as high as 2300 μg/day, which required intervention from the palliative care team.
At the time of intervention, the patient was isolated in a sterilized room after transplantation. In addition to the major complaint of pain in the lower left abdomen, upon palpation, the patient complained of pressure pain throughout the abdomen; he also complained of joint pain in the legs when the abdominal pain intensified. Computed tomography revealed changes showing pancreatitis and mild intestinal edema, which was considered to be a sign of GVHD (Fig. ).
Given the intense acute pain caused by GVHD, the fentanyl dose was increased again to 2700 μg/day; however, the frequency of the rescue dose for pain (equivalent to 1-h dose of continuous infusion) did not decrease below 15 times per day, and continuously increasing the dose did not reduce the frequency of the rescue dose. After the opioid was switched to 90 mg/day of oxycodone injections, the patient continued to experience pain, and there was no change in the frequency of oxycodone rescue doses (Table ).
The patient’s general condition improved, and he did not require isolation. Despite attending school in the hospital, there was no improvement in his complaints of pain, and just before entering junior high school, he expressed anxiety about friends, learning, and whether he would be understood by the teachers. Considering the possibility of opioid overdose in response to complaints of nausea and fatigue, dose reduction was planned; however, he exhibited strong resistance. Furthermore, he became irritable, and his mental instability became evident as exhibited by violent outbursts.
Computed tomography revealed no findings that caused physical pain. His pain was considered to have alleviated; thus, health professionals involved in his care (that is, pediatrician, pediatric psychiatrist, palliative care team, ward nurse, child medical care support provider, and childcare worker) examined the possibility of mental anxiety resulting in the lowering of pain threshold and the possibility of chemical coping.
Expecting to use less opioid, we initiated duloxetine, which exerts an antidepressive effect and adjuvant analgesic effect, at a dose of 10 mg/day. Furthermore, to address the patient’s mental anxiety, a meeting was held with the teacher whose class the patient was expected to attend. The new school staff cooperated so that the patient could attend the same class as his good friends. To address the patient’s drug use, upon suspicion that the sudden increase in blood concentration due to administration of rescue doses of opioid injections could have caused chemical coping, switching to oral opioids was attempted; however, on a pain scale (scale of 0 to 5), the patient assessed that the rescue doses of intravenous oxycodone had reduced his pain from 5 to 1.2 points, whereas the oral oxycodone immediate-release preparation had only reduced pain from 5 to 4.5 points; thus, switching to oral drugs was not successful.
We believed that the rescue dose of intravenous oxycodone resulted in a sudden increase in blood concentration, and the administration of the rescue dose could have been a coping behavior. An explanation regarding opioids in general and the possibility that the number of rescues will not decrease for purposes other than analgesia (such as antianxiety) was shared with the patient and his family members who provided the consent; thereafter, we decided to lower the concentration of intravenous oxycodone without informing the patient of the timing of dose reduction.
After approximately 1 month, the intravenous oxycodone dose was gradually reduced to 3 mg/day; however, there was no major change in the frequency of rescue doses. After the patient was informed that the intravenous oxycodone had been reduced to a dose that had been ineffective as an analgesic, we prescribed 200 mg of acetaminophen and 100 mg of ibuprofen to be taken as needed. Subsequently, oxycodone infusion was discontinued, and the patient did not complain of pain. Thereafter, he expressed no desire for opioid use and was discharged. Currently, he is being treated on an outpatient basis and is opioid-free.


In May 2016, a 38 year-old nulliparous woman at approximately 16 weeks’ gestation sought care for a one-day history of fever, rash, myalgia, arthralgia, and headache. Her only significant medical history was well-controlled high blood pressure. Diagnostic testing for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, and human immunodeficiency virus (HIV) (i.e., TORCH) performed at 10 weeks’ gestation was negative. At the time of her visit, the patient agreed to participate in an ongoing study of acute febrile illness, which collected blood, urine, and nasopharyngeal specimens for diagnostic testing [].
ZIKV RNA was detected in serum by RT-PCR one day after symptom onset; serum IgM testing and urine RT-PCR were both negative. The patient was enrolled in the Zika virus Persistence study [], for which serum, whole blood, urine, saliva, and vaginal secretions were collected weekly for 1 month and subsequently every 2 weeks thereafter. Collected serum specimens were tested for ZIKV, dengue virus, and chikungunya virus nucleic acid by RT-PCR [], and for anti-ZIKV IgM and anti-dengue virus IgM and IgG antibodies by ELISA [].
ZIKV RNA was detected in serum on days 1, 15, 22, 29, 36, 50 and 54 post illness onset (i.e., 18 – 24 weeks’ gestation) (). The patient was referred to a maternal-fetal medicine (MFM) specialist at 20 weeks’ gestation due to a positive quadruple screen test, 1:8 suggestive of Down syndrome, and a positive test for ZIKV infection. At approximately 24 weeks’ gestation, a level II ultrasound demonstrated generalized edema predominantly localized to the upper portion of the fetus’ body, a small amount of ascites, a single umbilical artery, and the absence of cardiac activity consistent with fetal demise. The patient was admitted to a hospital the following day for labor induction. TORCH testing was repeated, testing was performed for Lupusanticoagulant, and urine and serum were screened for drug and toxins, all of which were negative. The fetus was delivered vaginally at 24 weeks’ gestation in breech position approximately 8 hours after the initiation of labor induction. No cardiac or respiratory activity was present in the fetus at birth consistent with the diagnosis of fetal demise. Fetal weight was 3,289 grams. The fetus was edematous and macerated, and skin desquamation was present in the upper and lower extremities. The abdomen had skin discoloration suggestive of possible hematoma. Thinning of the umbilical cord at insertion site was noted. No dysmorphic features or neural tube defects were observed, and no clinical stigmata of Down’s syndrome were present. A retained placenta requiring a dilation and curettage complicated the mother’s clinical course. She recovered satisfactorily and was discharged home the following day. Parental consent was not provided for fetal autopsy; however, consent was given to examine the umbilical cord and placenta.
The placenta weighed 213 grams and measured 12 × 11.3 × 2.8 cm. The fetal and maternal membranes were well vascularized and the umbilical cord was inserted at the margin, measuring 23 × 1 cm, with two blood vessels present. The maternal surface had complete cotyledons, and transverse sections revealed spongy tan parenchyma. Upon microscopic evaluation, the placenta had patchy villous edema. Karyorrhectic debris was present around vessels within edematous villi, and larger sclerotic, avascular villi often had associated perivillous fibrin deposition. Stippled, deeply-basophilic calcifications were scattered within multiple villi. Multifocal aggregates of plasma cells were present within the decidua. Histologic findings were nonspecific, consistent with findings seen with intrauterine fetal demise and/or circulatory issues within the placenta, though the presence of plasma cells and other mononuclear cells within the decidua has been described as a sign of chronic antigenic stimulation []. ZIKV RNA was detected by RT-PCR in a specimen of placenta; however, ZIKV antigen was not detected by immunohistochemistry.
The patient was followed as part the Zika Virus Persistence study protocol. RT-PCR testing did not detect ZIKV RNA at 64, 78, and 92 days post-illness onset (). On day 120 after illness onset, ZIKV RNA was detected at low levels in a serum specimen. All serum, urine, saliva and vaginal secretions collected thereafter were negative by RT-PCR. Anti-ZIKV IgM antibody was first detected in serum on day 15 post-illness onset and was last detected on day 78 post-illness onset (). The same specimens were also tested by anti-DENV IgM ELISA, and all were negative. Anti-DENV IgG antibody was detected by ELISA in the specimen collected on the first day of acute febrile illness (week 16 gestation), demonstrating previous DENV infection. Further analysis of neutralizing antibodies by plaque reduction neutralization test (PRNT) on the same specimen [] [] demonstrated high titers against DENV−2, low titers to DENV−1, −3, and −4, and no titers against ZIKV, which together suggested prior infection with DENV−2. Specimens collected in the weeks following the initial infection demonstrated a robust neutralizing antibody response to ZIKV, including greater than 4-fold increase in titers against all DENVs, consistent with antibody response to secondary flavivirus infection [].


A 17-year-old Chinese Han man was admitted with a 23-day history of edema, fatigue, and subsequent anuria. He had no fever. Ten days before admission, his serum creatinine was 19.4 mg/dL, and urinalysis revealed proteinuria 1+ and hematuria with 228 red blood cells/high-power field (HPF). He was positive for perinuclear ANCA (pANCA) by immunofluorescence. He received hemodialysis and renal biopsy and was referred to our hospital. He had suffered from hyperthyroidism for 7 years and had been prescribed thiamazole and propylthiouracil (PTU) for 3 years. Moreover, he had a 5-year history of allergic rhinitis and allergic asthma. He had no family history of hypertension, glomerulonephritis or end-stage renal disease, and he had no drug addiction.
On admission, the physical examination revealed a blood pressure of 128/73 mm Hg, temperature of 36.5°C, heart rate of 78/min, and respiratory rate of 20/min. The patient was anemic, although further systemic clinical examination was unremarkable.
The laboratory data revealed serum creatinine of 12.3 mg/dL and interleukin-6 of 66.0 pg/mL (normal range: 0–0.64 pg/mL). The patient's urinalysis revealed proteinuria 1+ and dysmorphic red blood cells >100/HPF; he was positive for pANCA by immunofluorescence, and anti-MPO antibody was shown to be positive at 55.0 RU/mL by enzyme-linked immunosorbent assay. Anti-glomerular basement membrane antibody and antinuclear antibody were negative. The ophthalmological examination excluded tubulointerstitial nephritis with uveitis (TINU), and positron emission tomography-computed tomography scan indicated no tumor or infection.
The renal histology showed diffuse destruction of glomerular structure with crescents and severely ruptured Bowman capsules (Fig. ), which were surrounded by granulomatous inflammation, massive destruction or disappearance of tubules, and extensive interstitial infiltration of lymphocytes, monocytes, eosinophils, and plasma cells, with focal lymphocyte aggregation into “germinal centers” (Fig. ). Immunofluorescence microscopy showed little, if any, deposition of immunoglobulin or complement in the glomeruli and tubulointerstitium. Immunohistochemical staining (Fig. ) showed that the interstitial infiltrated cells were positive for CD20 (++), CD3 (+), CD138 (++), and Bcl2 (+), and negative for CD23, CyclinD1 and CD30.
Because of the severe TI injury observed in his kidney specimens, we detected anti-mCRP antibodies. The patient was strongly positive (112%) for serum anti-mCRP antibodies. As illustrated in Figure , the anti-mCRP antibody titer was 1:800, the subclasses of immunoglobulin G (IgG) were IgG2 and IgG3, and the major epitope was amino acids (a.a.) 35 to 47. Eight months later, the titer was still 1:800, while the main IgG subclass was IgG1.
The patient received 7 rounds of plasmapheresis, 3 pulses of methylprednisolone therapy (500 mg per pulse), and oral prednisolone (50 mg/d). Rituximab (500 mg) was used after the plasma exchange treatment. ANCA was negative, while anti-mCRP antibodies remained positive. The patient was dependent on hemodialysis.


The first patient is a 47-year-old man late after Mustard procedure for TGA. The tricuspid valve (systemic atrioventricular valve) was replaced two years before VAD implantation because of severe regurgitation. After tricuspid valve surgery he developed symptoms of advanced heart failure (New York Heart Association [NYHA] class IIIb) despite optimal medical therapy. He was screened for cardiac transplantation and rejected due to pulmonary hypertension (mean pulmonary artery pressure 29.7 mm Hg, transpulmonary gradient 12.7 mm Hg, estimated pulmonary vascular resistance 4.2 Woods Units). SRV function was poor (2D global longitudinal strain [GLS] −4.7%, fractional area change [FAC] 9.2%). The subpulmonary left ventricular function was reasonable. The patient showed advanced symptoms of heart failure and, consequently, was screened and accepted for VAD implantation. Pre-operatively, the patient was optimised with inotropic support and was in INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) level 3 at the time of surgery. Through median re-sternotomy and with cardiopulmonary bypass, a VAD (HVAD, Medtronic, USA) was implanted in the SRV after resection of multiple trabeculations in the SRV cavum. Because of anatomical considerations, the VAD was positioned mid-basally instead of apically, which is common for VAD implantation in the left ventricle (Figs. and ). Postoperative transoesophageal echocardiography (TEE) demonstrated normal VAD inflow and outflow signals and good VAD performance. Recovery was uneventful for 13 days. Then, a re-operation was necessary because of cardiac tamponade; following re-operation patient recovered well. Shortly after discharge, the patient suffered a haemodynamically tolerated sustained monomorphic ventricular tachycardia (185/min), probably originating from the surgical scar, which was terminated with procainamide. Eight months postoperatively, an ischaemic stroke occurred under clopidogrel and an adequate international normalized ratio (INR), with mild cognitive sequelae. A risk factor in this may have been the aortic valve, which showed reduced opening after VAD implantation. His target INR was raised. His maximum workload (measured with bicycle ergometry) is still improving from 70 Watts pre-implantation, to 80 Watts after 6 months of VAD support, and to 90 Watts currently. More than 1 year postoperatively, the patient is doing well and functioning in NYHA class II.


The second patient is a 54-year-old man with CCTGA, who underwent tricuspid valve replacement with a bioprosthesis and mitral valve annuloplasty 2 years before VAD implantation, the latter of which was complicated by partial ring dehiscence. The defect was closed percutaneously with 2 vascular plugs. In 2017, he received an ICD for primary prevention because of a poor SRV function. Recently, his clinical condition deteriorated rapidly and he was admitted because of congestion. He was rejected for cardiac transplantation because of renal dysfunction and, consequently, screened and accepted for VAD implantation. Transthoracic echocardiography (TTE) confirmed the poor SRV function (GLS −2.0%, FAC 7.3%). Pre-operative admission was prolonged due to biliary pancreatitis, which was treated with laparoscopic cholecystectomy. At the time of surgery, the patient was in NYHA class IV, INTERMACS level 2. Because of a decline in subpulmonary left ventricular function, treatment with levosimendan (Orion Corporation) was initiated. The VAD was implanted through a left-sided anterolateral thoracotomy combined with upper hemisternotomy because of a relatively dorsolateral position of the SRV and favourable anatomy for this approach. Again, multiple trabeculations were resected in the SRV cavum before the VAD (HVAD, Medtronic, USA) was implanted. Early after surgery, VAD flow dropped due to a deviation of the inflow cannula towards the septum resulting in obstruction of the inflow cannula. The cannula was subsequently repositioned. Seven days after VAD implantation, the patient was transferred to the coronary care unit. The remaining post-operative period was uneventful and patient is about to be discharged home.
Peri-operative challenges in the first case included the lack of space between the SRV and the sternum, and the trabeculations in the SRV. The former resulted in mid-basal insertion of the VAD instead of the more apical position that is common for VAD implantation in the left ventricle (Figs. and ). The latter necessitated resection of multiple trabeculations to prevent obstruction of the inflow cannula. The need for resection of trabeculations was expected in both cases, as pre-operative imaging clearly showed a heavily trabeculated SRV in both patients. This approach has been described previously []. In our second case, in addition to resection of trabeculations, a different surgical approach was used because of a relatively dorsolateral position of the SRV. In both patients, the challenging positioning of the inflow cannula could be partially explained by the presence of a tricuspid valve prosthesis, making TEE-guided localisation of optimal inflow cannula position less evident.
In general, SRV patients may have complex cardiac and thoracic anatomy, for example dextrocardia or situs inversus. As these cases demonstrate, anatomical variations in SRV patients require a patient-tailored surgical approach for VAD implantation (median (re)sternotomy versus lateral thoracotomy and upper hemisternotomy). An alternative device position should be considered when lack of space prevents apical implantation of the VAD, and inflow cannula orientation is of paramount importance for unobstructed VAD inflow. Pre-, intra- and post-operative imaging (for example with computed tomography angiography, epicardial/transoesophageal echocardiography, and transthoracic echocardiography, respectively) is crucial to plan and evaluate the operative approach [].


Our patient was a 71-year-old Japanese man who had undergone the Bentall procedure and biological aortic valve replacement for the treatment of descending aortic aneurysm and aortic regurgitation at 70 years of age. Thereafter, his renal function had been normal (serum creatinine level, 0.93 mg/dl) without hematuria and proteinuria. Two months before admission, he had appetite loss, malaise, and gross hematuria. One month before admission, he noticed purpura on his lower extremities. A laboratory examination conducted by his primary care physician showed anemia (hemoglobin, 9.2 g/dl), thrombocytopenia (platelet count, 10 × 104/μl), hematuria, and proteinuria. Therefore, he was referred to our hospital for further management.
Upon admission, his body temperature was 36.9 °C, and his blood pressure was 120/60 mmHg. Anemia, edema, and symmetrically distributed palpable purpura of the lower extremities were observed. He had no characteristic physical findings of infective endocarditis, such as Osler nodes, Roth spots, and Janeway lesions. Cardiac auscultation revealed 2/6 systolic reflux murmur at the cardiac apex. Blood analysis showed that the patient’s serum creatinine level was elevated at 2.34 mg/dl, and his serum hemoglobin level was reduced at 7.6 g/dl. Urinalysis showed proteinuria at 0.74 g/g Cr and microscopic hematuria. PR3-ANCA level was elevated at 163 IU/ml (normal range, < 10 IU/ml). The patient had negative test results for hepatitis B antigen, hepatitis C antibody, cryoglobulin, antistreptolysin O, antinuclear antibody, immune complex, and myeloperoxidase-ANCA. Serum complement C3 was mildly decreased, whereas C4 was normal. Laboratory data obtained at admission are summarized in Table . No abnormalities were found in the patient’s chest x-ray or electrocardiogram. Streptococcus species was detected from two separate blood culture bottles. On the third hospital day, renal biopsy was performed. Histological analysis revealed that 54% (6 of 11) of glomeruli showed partial fibrinoid necrosis with fragmentation of glomerular tufts (Fig. a), and 27% (3 of 11) of glomeruli showed cellular crescents (Fig. b). No fibrocellular or fibrous crescents and no endocapillary proliferation were found. The mesangium showed no increase in cells or matrix. The tubulointerstitium partially showed neutrophilic and lymphocytic infiltration in the peritubular capillary and atrophy (Fig. c). Fibrinoid necrosis was not observed in vessel walls. Immunofluorescence microscopy showed no deposition of immunoglobulins and complement factors. Electron microscopy showed small amounts of nonspecific electron-dense deposits in subendothelial areas and the paramesangial area. At this point, the patient met the modified Duke criteria for definitive infective endocarditis [] (mitral valve vegetation on echocardiography, two positive blood cultures of Streptococcus species drawn 3 days apart, glomerulonephritis). On the eighth hospital day, transesophageal echocardiography revealed mitral valve vegetation. On the 12th hospital day, spinal magnetic resonance imaging showed pyogenic spondylitis at T7/T8 and L4/L5. On the basis of these findings, the patient was diagnosed with rapidly progressive PR3-ANCA-positive necrotizing crescentic glomerulonephritis complicated by Streptococcus infective endocarditis. Antibiotic therapy including cefazolin and penicillin G followed by oral administration of ampicillin was provided without immunosuppressive agents. Thereafter, his renal disease, endocarditis, and pyogenic spondylitis improved. He was discharged from our center on the 73rd hospital day. He has since received regular outpatient treatment in our department. At 7 months after discharge, his serum creatinine level had decreased to 1.43 mg/dl, his proteinuria had decreased to 0.15 g/g Cr, and his hematuria had decreased to 1.1 red blood cells per high-power field. His PR3-ANCA level had decreased to within the normal range (Fig. ).


A 67-year-old woman presented with progressive shortness of breath and bilateral legs edema for 3 weeks. In addition, generalized pruritus and poor appetite were noted. She reported no obvious decrease in urine output. Her medical history included untreated diabetes mellitus and chronic kidney disease (CKD). She denied use of Chinese herbs and pain killers recently. She denied fever, chest pain, abdominal pain or tarry stool.
Upon arrival to the ED, she was oriented and her vital signs were as followings: a heart rate of 83 bpm, blood pressure of 198/91 mmHg, respiratory rate of 18, body temperature of 37 °C and oxygen saturation of 97% in room air. Chest auscultation revealed crackles at both bases without heart murmurs or friction rubs. Pitting edema over bilateral lower limbs up to the knees was noted. Physical examination was otherwise unremarkable. The laboratory data revealed marked elevated level of serum creatinine (548 μmol/L) and blood urea (35 mmol/L). Urine analysis revealed presence of proteinuria (3+ at the dipstick) but serum albumin (32 g/L) was not obviously reduced. Arterial blood gas showed metabolic acidosis. Electrocardiogram (ECG) showed normal sinus rhythm with low voltage QRS (Fig. a), and chest X-ray revealed an enlargement of the cardiac silhouette (Fig. b). PoCUS was applied and included assessments of lung, heart and inferior vena cava (IVC). Sonography disclosed a large amount of pericardial effusion without right ventricle collapse sign (Fig. a), normal lung sliding signs with one B line (Fig. b) and mildly distended IVC (Fig. c).
Uremic pericarditis was highly suspected. Intensive daily hemodialysis was initiated and the amount of fluid removal was 1 kg per day. She tolerated dialysis well and her symptoms improved after five days. Daily hemodialysis was then shifted to standard hemodialysis (three times a week). A follow-up echocardiography showed resolution of pericardial effusion. The patient was discharged in a stable condition.


The patient is a 52-year-old African American male with an unwanted diverting loop ileostomy who was scheduled for an elective stoma reversal. Originally, the loop ileostomy was created for fecal diversion after a large perineal defect was made for the treatment of necrotizing fasciitis of the perineum. A high splenic flexure, foreshortened colonic mesentery, and morbid obesity precluded performing a diverting colostomy at that time. Of note, the patient had no family history of HO or abdominal surgical history prior to the ileostomy creation.
During the reversal of the loop ileostomy, a circumferential incision was made at the mucocutaneous junction. Dissection was carried towards the serosal surface of the small bowel with electrocautery. There were significant adhesions between the small bowel and surrounding soft tissue which was much denser than expected. At that time, the base of the ostomy was reached and a dense structure was identified by palpation. It was circumferential in both limbs of the loop ileostomy. It was hard and fixed with a bone-like consistency. We encountered difficulty in freeing the small bowel from this circumferential dense structure, and this, combined with the patient's body habitus, rendered it difficult to take the stoma down safely through the peristomal incision. As a result, we converted the operation to an open procedure using a lower midline incision to reverse the ileostomy. After significant lysis of adhesions, the ileostomy was reached from the midline incision, and the hard structure was excised circumferentially using a combination of sharp dissection with Metzenbaum scissors and Bovie electrocautery. Upon gross inspection, it was observed that the structure was seated at the level of the rectus abdominis muscle and formed a complete circle around the ileostomy. A portion appeared to have the consistency of thin connective tissue, while the majority of the specimen appeared osseous. The specimen grossly consisted of three irregular portions of ragged skeletal muscle and bone measuring 5.5, 7, and 12.5 cm in the greatest dimension (). The skeletal muscle and bone were intertwined with flattened strands of bone interdigitating with the skeletal muscle fibers. Delicate, branching wisps of bone protruded from the specimen. No foreign body was identified. The specimen was radiographed using the Faxitron and showed both trabecular and cortical bone within the skeletal muscle (). Microscopically, both thick cortical bone and trabecular bone with normocellular bone marrow were found within the skeletal muscle. Bone encircled and was immediately adjacent to skeletal muscle fibers (Figures and ).
The patient had follow-up visits after ileostomy reversal at weeks 2, 3, 7, 10, and 16. He developed transient fecal incontinence given the extensive nature of his perineal wound, which was successfully treated with pelvic floor biofeedback therapy by week 10. His ileostomy and midline wounds healed without abdominal pain, hernias, or signs of recurrence.


A 33-years-old male was admitted into our hospital after 3 hrs of intermittent chest pain. Previously, the patient was admitted to our hospital and diagnosed with first-degree atrioventricular conduct block and coronary artery ectasia, which was conservatively treated with aspirin (100 mg/qd, atorvastatin 20 mg/qd) on a routine basis. After 7–8 episodes of diarrhea, the patient experiences a similar chest pain to previous episodes. Electrocardiography (ECG) was performed immediately, which disclosed ST elevation in inferior leads (II, III and avF). The patient was defibrillated after developing a sudden ventricular fibrillation.
On admission, his pulse was recorded as 72/min and blood pressure (BP) as 120/70 mmHg. In laboratory examinations, cardiac enzyme contents were as follows: creatine kinase (CK)413 IU/L, high-sensitivity troponin I (hs-TnI) 3.303 μg/L, creatine kinase muscle/brain mass (CK-MBmass) 36.94 μg/L. The consequent diagnosis was acute ST elevation myocardial infarction (STEMI). The patient underwent elective coronary angiography, which revealed normal left main coronary artery (LMCA), left anterior descending (LAD) middle segment light stenosis with aneurysm-like ectasia and aneurysm-like ectasia of proximal left circumflex artery (LCX), as well as aneurysm-like ectasia of middle segment and thrombus in the distal segment of right coronary artery (RCA) (Fig. a-c).
Despite angiographic detection of a thrombus, conservative therapy (aspirin 100 mg/qd, ticagrelor 90 mg/tid, atorvastatin 20 mg/qd) appeared the optimal treatment choice. For further examination of cardiac function, echocardiography was performed, which revealed right and left ventricle regional wall motion abnormalities, left ventricle diameter of 55 mm, and left ventricle ejection fraction (LVEF) of 56%.
During history taking, the patient provided information on the medical history of his father who was admitted to another hospital due to a similar complaint of chest discomfort and underwent coronary angiography, which showed ectasia of the middle to distal segment of RCA and mid segment of LAD and normal LMCA, LCX (Fig. d-f). For analysis of the genetic relationships, high throughput sequencing testing was conducted, as depicted in (Fig. ).
After 1 year of conservative therapy, the patient was re-admitted to our hospital due to short episodes of chest pain, which usually ended within a few seconds. Computed tomography angiography (CTA) revealed normal LMT, slight calcification and ectasia of LAD, LCX, and RCA (Fig. ). Rivaroxaban 10 mg Qd was selected for anticoagulant therapy, along with atorvastatin 20 mg/qd.


A 41-year-old male presented to the urology OPD in September 2014 with complaints of colicky pain in the right flank and dysuria of 3 months duration. Examination revealed right renal angle tenderness. The renal function was normal, and an ultrasonography revealed 2.3 × 1.5 cm renal abscess, 1.5 cm left calyceal cyst, 2.8 mm right renal calculus, with a normal bladder, and post-void residual urine (PVRU) of 16 ml. A mild splenomegaly (13 cm), with multiple enlarged lymph nodes in periumbilical region, largest measuring 20 × 19 mm, was also identified; there were no other nodes and no free fluid in the abdomen. A FNAC from lymph nodes was performed which was inconclusive; however, a clinical diagnosis of tuberculosis was made and the patient was started on antitubercular treatment.
The patient completed the prescribed antitubercular treatment and remained asymptomatic for 2 years. No follow-up scans were done. In October 2016, the patient again presented to the urology OPD with complaint of recurrent pain in the right flank for 10 days. The pain was moderate in intensity, radiating to the back along with high-grade fever with rigors. There were no urinary complaints this time. Abdominal examination was normal, the renal function was normal, no scans were done, and the patient was referred to orthopedics for treatment of back pain, wherein symptomatic treatment was given. In November 2016, the patient presented to the surgical oncology OPD with complaints of painless progressive ulceroproliferative lesion in the oral cavity, fever, and abdominal pain. On examination of the oral cavity, there was a grayish-brown ulcerative growth starting from the first premolar and continuing till retro molar trigone (RMT) region, involving the right lower gingivobuccal sulcus (GBS), alveolus, and floor of mouth (Fig. ). Level Ib lymph nodes were palpable in the right neck. The abdominal examination revealed a hard mass in the umbilical and another in the left lumber area with well-defined borders and limited mobility in the lumber mass while the paraumbilical mass was mobile. There were no other significant findings on abdominal and systemic examination.
The CECT of the oral cavity and neck was performed that showed ill-defined thickening in the right inferior gingiva buccal sulcus (premolar and molar region), buccal mucosa, and RMT measuring approximately 54 × 30 × 19 mm; the mass was seen infiltrating the masseter muscle, and destruction of the right inferior alveolus in the molar region and floor of mouth medially was also noted (Fig. ). Multiple subcentimeter neck nodes level I and II were seen in the CT scan with the largest of size 25 × 18 mm in the right submandibular region. Abdominal CECT showed a matted lymph node mass in the mesentery of the small bowel and another well-defined mass lesion just posterior to the spleen and superior to the left kidney. The left adrenal was not identified separately (Fig. ).
A punch biopsy was taken from the right buccal mucosal lesion that showed features suggestive of round cell tumor (Fig. ). The IHC was performed that showed positivity for CD45, CD 20, CD 10 (immunoreactive score of 4+), and bcl-2 (immunoreactive score of 2+) (Fig. ). The KI-67 showed immunoreactive score 4+ in > 90% cells (Fig. ). The CD3, CD 138, CD 99, ALK-1, CK, chromogranin A, desmin, and HMB-45 were negative (Fig. ). The morphological and IHC features a diagnosis of diffuse large B cell lymphoma (DLBCL). The patient was started on R-CHOP regime and had complete response with regression of the disease after 6 cycles. He continued on maintenance therapy for 1 year and is alive and disease free 14 months after completion of the treatment and stoppage of maintenance therapy.


The patient was a 45-year-old man, previously healthy, with a complaint of 4 days of high fever and dry cough. When he presented to the emergency room (ER) of our hospital, he was conscious but had severe shortness of breath and associated with nausea and vomiting. He had clammy and cold extremities. Examination showed bilateral wet rales at the bottom of the lungs, regular but fast heart rate, and benign abdomen. Electrocardiogram (ECG) showed sinus tachycardia, complete right bundle branch block, and ST-T changes (Fig. A). Chest computed tomography revealed diffuse bilateral patchy infiltrates and ground-glass opacity. Presumptive diagnosis was FM with cardiogenic shock. Continuous oxygen, dobutamine, norepinephrine, diuretic and empiric imipenem and vancomycin, IVIG (20 g per day for 5 days), vitamin C, coenzyme Q 10 were started immediately and we did not use any steroids or immunosuppressive agents. Despite clinical treatment, the patient did not show any improvements. After explaining the disease condition and prognosis to the patient's family, he was transferred to the EICU from the ER in 12 hours. The patient's condition deteriorated drastically and tracheal intubation, VA-ECMO, and continuous renal replacement therapy (CRRT) were initiated 6 hours after EICU admission. A transthoracic echocardiogram (TTE) showed global hypokinesia and severely impaired left ventricular (LV) function with an ejection fraction (EF) of 18%. Tests to identify the etiologic agent were performed and all negative, including enterovirus, parvovirus B19, adenovirus, influenza virus assessed by PCR at nasopharyngeal swab and CMV, EBV, HSV, mycoplasma assessed by serology in the plasma. Laboratory measurements showed thrombocytopenia, elevated levels of cardiac enzyme, liver enzyme, blood urea nitrogen, creatinine, and inflammatory markers (Table ).
Heparin was continuously administrated by an infusion pump to maintain an activated partial thromboplastin time (APTT) of 70 to 100 seconds. To guarantee the level of hemoglobin > 9 g/dL and platelet > 50,000/μL, blood transfusion was administered intermittently. To prevent the distal leg ischemia, a catheter connected superficial femoral artery with femoral artery was required. To recover from peripheral circulatory failure, the initial flow rate was set as 4.5 L/min. His cardiac enzyme and liver enzyme gradually declined to normal.
On the first day of EICU admission and after ECMO administration, the patient experienced short ventricular tachycardia (VT) which could be reversed by antiarrhythmic drugs (Fig. B). However, he experienced refractory VT and ventricular fibrillation (VF) 2 days later. Unfortunately, the electrical storm could not be reversed by the electric cardioversion, defibrillation, cardiopulmonary resuscitation (CPR), and antiarrhythmic drugs (Fig. ). The bedside echocardiography showed LVEF was lower than 10% and aortic valve hardly opened during left ventricular contraction, so IABP was administered with an initial pace ratio of 1:2 on the following day (Fig. ). After the IABP support, he experienced atrial fibrillation which could be reversed by antiarrhythmic drugs (Fig. C).
Daily bedside echocardiography demonstrated gradual improvement in cardiac contractility. The flow rate of ECMO and the pace ratio of IABP was decreased, according to the vital signs and indicators of peripheral circulatory failure (e.g., lactic acid, mixed venous oxygen saturation, and arterial blood gas analysis).
ECMO was able to be withdrawn on hospital day 11 when transesophageal echocardiogram (TEE) showed estimated LVEF of 50% and the patient was weaned from IABP successfully on hospital day 14. He was extubated on hospital day 20 but required tracheotomy. The patient stayed in EICU for 33 days and was discharged on the 81th day after admission, with all his laboratory tests returned to normal (Table ). Electrocardiogram showed sinus rhythm with complete right bundle branch block (Fig. D). Echocardiography showed normal cardiac chambers and normal wall motion with EF 67%. His stay in the hospital was complicated by hospital-acquired pneumonia, acute renal failure, gastrointestinal bleeding, and critical illness myopathy.


In 2007, a previously healthy 27-year-old Caucasian female was referred to the surgical outpatient clinic for analysis of abdominal pain. The upper right quadrant pain had started a few months earlier and was intermittently present up to one hour following food ingestion. Jaundice, fever, vomiting, melena or altered bowel habits were absent. The family history for cancer or MEN-1 disease (Multiple Endocrine Neoplasia Type 1) was unknown
Physical examination only revealed mild pain following deep upper quadrant palpation without signs of peritonitis. As gallbladder disease was likely, ultrasonography of the abdomen was advised that demonstrated cholecystolithiasis. The morphology of the gallbladder was deemed normal as were all other abdominal organs. The patient was planned for a laparoscopic cholecystectomy that was performed uneventfully a few months later.
A routine histopathologic examination showed a 0,3 mm NET in the adventitia of the gallbladder with clear resection margins (). A subtype was not defined. The patient was not presented in our multidisciplinary oncology meeting. A yearly out-patient follow-up with focused echography of the liver during 5 years showed no recurrence of disease. Follow-up was stopped. A recent telephone contact assured that patient is currently disease-free and in excellent health. Surprisingly, histological revision of her gallbladder by our pathologist dictated by a regional GBC research initiative showed a paraganglion of the gallbladder instead of a NET.


A 63-year-old man was admitted to our hospital with discomfort and upper abdominal pain that had started 1 month before. He had a history of hypertension and was treated with Levamlodipine Besylate Tablets. He was admitted in local hospital with 1-month history of intermittent pain that progressively worsened and was located in the epigastrium. The patient did not experience nausea, vomiting and diarrhea. Gastroscopy performed at another hospital revealed superficial gastritis with erosion. Computed tomography (CT) of the abdomen at the local hospital showed a linear, hyperdense, foreign body in the lesser curvature of gastric antrum that had penetrated through the posterior wall of the gastric antrum (Fig. A–F). He was then referred to our hospital for further treatment. On admission, the vital signs were stable and body temperature was 36.7°C. Physical examination revealed tenderness in the right upper quadrant and epigastrium. Laboratory investigations reveled a normal white blood cell count and other laboratory tests were found in normal reference ranges. We suspected that if the patient has a history of fish bone ingestion, As it is been a long time since the patient felt discomfort in the upper abdomen, the patient did not remember if there was a history of foreign body(such as fish bone, chicken bone or toothpick) ingestion. And because no foreign body was found in the gastroduodenum by gastroscopy, Hence, an explorative laparoscopic surgery was performed. The laparoscopic exploration found that severe adhesions were between the gastric antrum and the greater omentum, and we use an ultrasonic scalpel to dissect the adhesions carefully. Then, the foreign body was noted and safely removed laparoscopically (Fig. A–C), which was identified as a fish bone (length, 2.5 cm; diameter, 0.3 cm) (Fig. ). At last, we repaired the perforation and cover the site of the penetrated gastric wall with the omentum. After surgery, the patient underwent uneventful recovery and was discharged on postoperative day 7. During the 3 months of follow-up visit, the patient appeared healthy and did not report abdominal symptoms.


A 57-year-old male who had been diagnosed with an SCI at C3-C4 3 years before was admitted to the Chonnam National University Hospital Rehabilitation Center to participate in our program and was trained for 6 weeks. The right upper and lower limb motor functions differed when evaluated before entry into the program. Lower right leg motor function was good, but lower left leg function was poor. Before program entry, the patient could walk for about 10 m using a cane. He lacked severe medical and psychological problems and was not cognitively impaired.
The Angelegs Training program was scheduled for five 30-minute sessions per week for 6 weeks, for a total 30 sessions. Before program entry, he underwent three 30-minute pre-training sessions on the Angelegs. Training was conducted in the rehabilitation center of Chonnam National University Hospital; a single physical therapist supervised all training. The training program consisted of sit-to-stand and stand-to-sit movements, maintenance of standing balance for 5 minutes at a time, and walking for 15 minutes. He used a cane to maintain balance during training. Walking proceeded on flat ground for 10 m at a gait speed that was the best that the patient could attain (Fig. ). During the program, the patient received the physical and occupational therapies (30-minute sessions) he had previously been prescribed.
A physical therapist evaluated functional outcomes using range of motion (ROM) tests; the Manual Muscle Test (MMT); the Modified Ashworth Scale (MAS); the Korean-Modified Barthel Index (K-MBI); Functional Ambulatory Category (FAC) scoring; 3-dimensional dynamic posturography (PRO-KIN system, TecnoBody Srl, Dalmine BG, Italy); EuroQol-5D (EQ-5D) scoring; a 10-m walking test; a timed up-and-go test, and 3-dimensional gait analysis before (T0) and after training (T1). The patient walked 10 m a total of 10 times in the flat aisle and walked normally as during the gait analysis. In addition, the patient wore a portable gas analyzer (model K4B2, COSMED Srl, Rome, Italy) that measured the VO2 levels and the metabolic equivalent (MET).
The patient visited our rehabilitation clinic 6 weeks after the end of the program (T2) and underwent all tests again. There were no adverse events during these assessments.
The 10-m walk test (at a comfortable pace) time decreased from 89.00 s (T0) to 86.50 s (T1) and 86.47 s (T2). In the up-and-go test, the speed increased from 6.8 cm/s (T0) to 9.7 cm/s (T1) and 10.3 cm/s (T2) (Table ). However, the gait pattern did not differ at T0, T1, and T2.
MET and VO2 were measured to evaluate the patient's cardiopulmonary function. MET decreased from 4.6 (T0) to 4.1 (T1) and 3.4 (T2). VO2 decreased from 1208.1 mL (T0) to 1077.1 mL (T1) and 901.3 mL (T2). However, other physical functions showed no improvement, such as ROM, MMT, MAS, K-MBI, FAC, stride length, step width, or EQ-5D data change over time (Table ).