Objective Patients on outpatient insulin therapy are at a high risk of severe hypoglycemia and a high incidence of hypoglycemic coma. However, only a few studies have explored the risk factors for hypoglycemic coma in such patients. We retrospectively analyzed the clinical characteristics of diabetic patients who had developed hypoglycemic coma during outpatient insulin therapy.

Methods This study included 33 diabetic patients on insulin therapy who were transported to the hospital by ambulance for severe hypoglycemia. Patients with a Japan Coma Scale score <100 were classified as the non-coma group (n=18), while those with a score ≥100 (n=15) were classified into the coma group.

Results Patients in the coma group were significantly older, with a higher proportion of elderly patients ( ≥65 years of age), than those in the non-coma group. Although no marked difference in the basal insulin dose was observed between the two groups, the bolus insulin dose was significantly higher in the coma group. However, no marked differences in the disease type or renal function were noted between the two groups.

Conclusion An advanced age and bolus insulin dose are risk factors for hypoglycemic coma in diabetic patients on insulin therapy. Bolus insulin dose minimization should be performed in order to prevent hypoglycemic coma, especially in elderly diabetic patients.

Objective To clarify the associations between serum omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acid (PUFA) levels and obesity-related metabolic abnormalities in patients with type 2 diabetes.

Methods and Materials Data from 225 Japanese patients with type 2 diabetes were cross-sectionally analyzed. The serum levels of n-6 PUFAs [dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA)] and n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) were measured, and the estimated Δ-5 desaturase (D5D) activity was calculated based on the AA to DGLA ratio. The associations between the composition of PUFAs and obesity-related parameters, including the body mass index (BMI), waist circumference, alanine amino transferase (ALT) level, homeostatic model assessment of insulin resistance (HOMA-IR), and body fat percentage, as measured by a bioelectrical impedance analysis, were analyzed.

Results Among the PUFAs, the DGLA level had the strongest correlations with BMI (p<0.001), waist circumference (p<0.001), ALT level (p<0.001), HOMA-IR (p<0.001), and body fat percentage (p<0.01). AA was positively correlated and D5D was negatively correlated with several obesity-related parameters, while n-3 PUFAs did not have a constant correlation. A multivariate regression analysis revealed that the DGLA level was an independent determinant for HOMA-IR (β=0.195, p=0.0066) after adjusting for sex, age, BMI, and the ALT, triglyceride, and HbA1c levels.

Conclusion A high serum DGLA level was associated with obesity, body fat accumulation, a high ALT level, and insulin resistance in patients with type 2 diabetes. The measurement of the serum PUFA levels may be useful for evaluating metabolic abnormalities and estimating the dietary habits of patients.

Objective This report presents a part of a survey pertaining to drug burden in maintenance hemodialysis patients in Japan.

Methods A patient-reported questionnaire-based survey was conducted from September to November 2016 in six regions in Japan.

Patients A total of 700 patients (50-79 years old) on maintenance hemodialysis for >3 years and members of the Japan Association of Kidney Disease Patients (JAKDP) were provided with the questionnaire. They were randomly selected using stratified sampling according to patient distribution observed from the Japanese Society for Dialysis Therapy Renal Data Registry (JSDT JRDR).

Results A total of 524 (74.9%) patient questionnaires were evaluated [mean (standard deviation; SD) age, 66.6 (7.2) years; males, 63.4%; dialysis vintage, 16.9 (9.1) years]. Patients' age, gender, and regional distribution were similar to the JSDT JRDR. They were taking an average (SD) of 16.4 (8.34) and 16.3 (8.55) oral medications/day on dialysis and nondialysis days, respectively. A majority of the patients were taking ≥10 oral medications/day on dialysis (75.1%) and nondialysis (74.4%) days, with phosphate binders being the most taken (7.0 tablets/day). A similar proportion (74.4%, 72.9%, respectively) was taking ≥6 different types of oral medications/day. Most patients were taking oral medications 3 (31%, 33%), 4 (24%, 22%), and ≥5 times (31%, 30%) a day, respectively. The drug burden was similar on dialysis and nondialysis days and did not vary with dialysis vintage.

Conclusion The number, type, and frequency of oral medications in maintenance hemodialysis patients are high in Japan. The proportion of phosphate binders was highest among the prescription medications.

A 90-year-old man was referred to our hospital because of a positive fecal occult blood test. Colonoscopy revealed a lesion with multiple nodules covered with abundant mucus at the hepatic flexure. Computed tomography showed a dilated appendix attached distally to the hepatic flexure. Right hemicolectomy was performed, and the pathological examination revealed a mucinous appendiceal adenocarcinoma infiltrating the hepatic flexure without pseudomyxoma peritonei. The patient is doing well without recurrence 12 months postoperatively. Extraperitoneal drainage of the malignant ascites caused by the fistula may allow for an early diagnosis, while also making it possible to successfully resect the lesion, thus resulting in a favorable outcome.

The endoscopic and pathological features of early gastric mixed adenoneuroendocrine carcinoma (MANEC), as well as its carcinogenesis, remain largely unclear. Screening esophagogastroduodenoscopy was performed on an 80-year-old man, revealing 3 superficial elevated lesions. Endoscopic submucosal dissection (ESD) was performed, and the patient was diagnosed with intramucosal gastric cancer comprising mixed adenocarcinoma and neuroendocrine tumor, well-differentiated adenocarcinoma and well-differentiated adenocarcinoma, with negative margins. To our knowledge, this is the first report describing the endoscopic and pathological findings of synchronous triple gastric cancer incorporating mixed adenocarcinoma and neuroendocrine tumor completely resected with ESD.

Autoimmune pancreatitis (AIP) is a distinct subtype of pancreatitis, which is classified into type 1 and 2 based on the clinicopathological features. According to the international consensus diagnostic criteria, pancreas resection or core biopsy specimens are recommended to make an accurate histological evaluation. However, the usefulness of endoscopic ultrasonography (EUS) guided fine needle aspiration (FNA) for histological evaluation has also been reported. Furthermore, the simultaneous presentation of type 2 AIP and Crohn's disease (CD) is very rare, especially in the Asian population. Therefore, we herein report a case of type 2 AIP with CD, which was diagnosed using EUS guided FNA with a 22-gauge needle.

Traumatic tricuspid regurgitation (TR) is a rare cardiovascular complication in chest trauma. Changes in the left ventricle (LV) function after operation are unclear. A 61-year-old woman who had been involved in a traffic accident 1 month earlier presented with exertional dyspnea. Transthoracic echocardiography (TTE) showed severe tricuspid regurgitation (TR) accompanied by LV dysfunction due to anterior leaflet prolapse with papillary muscle rupture. After tricuspid plasty, the LV function improved, as evidenced by TTE and speckle tracking echocardiography. In conclusion, the early diagnosis of traumatic TR is important, and early surgical intervention might be effective for achieving ventricular function improvement.

A 62-year-old woman with takotsubo cardiomyopathy (TCM) accompanied by cardiogenic shock due to the obstruction of left ventricular outflow tract (LVOT) and massive mitral regurgitation (MR) was admitted to the emergency department. After successful treatment with intensive care, dobutamine stress-echocardiography was performed, which reproduced a dynamic LVOT gradient, severe MR and cardiogenic shock. A histological examination obtained from the right ventricular septum demonstrated hypertrophied and bizarre myocytes, with myocyte disarray. Besides TCM, a diagnosis of preexisting hypertrophic cardiomyopathy with latent obstruction was made. She was discharged with medical therapy including a beta-blocker, which would not be routinely employed in the treatment of a patient with TCM.

Legionella pneumonia is occasionally accompanied by renal complications; however, the cause of this remains unknown. We herein report a 70-year-old Japanese man with Legionella pneumonia who presented with hyponatremia, hypophosphatemia, and hypouricemia. The levels of urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase were remarkably high, indicating severe renal tubular damage. The presence of glycosuria and aminoaciduria as well as increased fractional excretion of uric acid and decreased tubular reabsorption of phosphate indicated that the patient's condition was complicated with Fanconi syndrome. After antimicrobial therapy, the electrolyte abnormalities and renal tubular damage were completely resolved.

We herein report the case of a 76-year old man with aquaporin-4-Immunoglobulin-G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD), in whom transient interstitial pulmonary lesions developed at the early stage of the disease. Chest X-ray showed multiple infiltrative shadows in both upper lung fields, and computed tomography revealed abnormal shadows distributed randomly in the lungs. Surgical lung biopsy showed features of unclassifiable interstitial pneumonia, characterized by various types of air-space organization, which resulted in obscure lung structure. This is the first report to describe the pathological findings of interstitial pneumonia, which may represent a rare extra-central nervous system complication of NMOSD.

A 65-year-old man was diagnosed with advanced non-small, non-squamous lung cancer. He was treated with chemotherapy containing bevacizumab as well as cisplatin and pemetrexed. After 2 courses of treatment, computed tomography revealed that his abdominal aortic artery was almost occluded by a thrombus; however, he had no ischemic symptoms. Heparin infusion and warfarin reduced the size of the arterial thrombus and the patient was subsequently treated with chemotherapy without bevacizumab. No thrombotic events occurred during the subsequent treatment. We later noticed a small organized abdominal arterial clot and calcification on a computed tomography scan taken before bevacizumab treatment. Atherosclerotic changes should be evaluated before the administration of bevacizumab.

Progressive fibrobullous changes in the residual lobes are sometimes observed after lobectomy. Aspergillus osteomyelitis is an uncommon infection that rarely occurs sternally. A 70-year-old man who had undergone lobectomy 12 years earlier was admitted to our hospital for chest pain. He was diagnosed with Aspergillus sternomyelitis based on sternal bone culture after an ultrasound-guided percutaneous needle biopsy. The fibrosis and right residual lung apex volume loss had gradually progressed over 12 years, and therefore, chronic pulmonary aspergillosis (CPA) with direct invasion sternal from the CPA was considered. Aspergillus sternomyelitis can develop from CPA as a late complication of lobectomy.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome that occurs as a complication in many clinical settings. Malignancy-associated HLH develops in patients with hematopoietic neoplasms, particularly in those with lymphoma, and its development in those with myelodysplastic syndrome (MDS) is uncommon. We herein report a case of HLH in a patient with low-risk MDS that was successfully treated with azacitidine. The prevalence of immune abnormalities among MDS patients and the immune effects of azacitidine have recently been elucidated, suggesting that MDS-associated HLH occurs as a result of immune impairment, and azacitidine improves this condition by restoring the immune system.

We herein report a rare case of methotrexate (MTX)-associated intravascular large B-cell lymphoma (IVLBCL) in a man with rheumatoid arthritis. Two episodes of a fever of unknown origin accompanied by elevated levels of serum lactate dehydrogenase and the soluble interleukin-2 receptor occurred within a year, so the patient was suspected of having an MTX-associated lymphoproliferative disorder. His clinical symptoms resolved after the cessation of MTX. However, after treatment with iguratimod, another disease-modified anti-rheumatic drug, markedly similar symptoms recurred, and random skin biopsies resulted in a diagnosis of IVLBCL. The patient received a rituximab-containing chemotherapy and achieved complete remission.

Cardiac ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy is a promising biomarker for dementia with Lewy bodies (DLB). However, we experienced a patient with cognitive decline, parkinsonism, and a decreased MIBG uptake who turned out to have HIV dementia. Normal dopamine transporter single-photon emission computed tomography reduced the possibility of comorbid Lewy body pathology causing the patient' s parkinsonism. The decreased MIBG uptake was most likely due to postganglionic sympathetic nerve denervation, which can also be caused by HIV. This case further emphasizes the importance of excluding other causes of autonomic neuropathy, including HIV infection, before interpreting MIBG scans.

A 50-year-old man with a family history of stroke and depression slowly developed brain lesions. Magnetic resonance imaging revealed hyperintense lesions in the diffuse white matter, external capsules, and temporal poles on T2-weighted imaging. A heterozygous mutation c.3879C>G in exon 24 of the NOTCH3 gene (p.Cys1293Trp) was detected, confirming a diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Exon 24 mutations are rather rare and this represents the first Japanese case of CADASIL.

We herein report two patients harboring the mutation N279K in microtubule-associated protein tau (MAPT), who showed parkinsonism with a disease duration within three years from the onset, evaluated by dopamine transporter (DAT) [¹²³I]N-ω-fluoroprophyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane single-photon emission computed tomography. We performed a quantification analysis, comparing five age- and severity-matched PD patients and six normal controls. The patients with the N279K mutation showed a more marked reduction in their DAT densities, especially in the caudate nucleus and anterior putamen, than the others. An early marked reduction in the DAT densities in the caudate nucleus and anterior putamen may be an early biomarker of patients with MAPT mutations.

An 82-year-old woman developed neck weakness and dysarthria with antibodies against acetylcholine receptor (AChR) and low-density lipoprotein receptor-related protein 4 (LRP4). Myasthenia gravis (MG) was diagnosed by edrophonium and repetitive nerve stimulation tests. Her symptoms resolved completely by immunotherapy. One year later, she presented with muscle weakness and bulbar palsy accompanied by atrophy and fasciculation. Her tendon reflexes were brisk, and Babinski's sign was positive. She was diagnosed with probable amyotrophic lateral sclerosis (ALS). Immunotherapy did not improve her symptoms, and she ultimately died of respiratory failure. MG and ALS may share a pathophysiology, including anti-LRP4 antibodies at the neuromuscular junction.

A 70-year-old Japanese woman presented to our hospital with gait disturbance and cognitive dysfunction. Since she had arthritis, lymphopenia, hypocomplementemia, and anti-nuclear and anti-double-stranded DNA antibodies, she was diagnosed with systemic lupus erythematosus (SLE). T2-weighted magnetic resonance imaging revealed bilateral hyperintensities in the putamen. Based on her cognitive impairment, muscle rigidity, and high levels of interleukin-6 in the cerebrospinal fluid, we believed she had developed a complication of a neuropsychiatric disease and administered corticosteroids and intravenous cyclophosphamide therapy. Her cognitive function fully recovered, and her gait disturbance improved. Attending to cognitive impairment in elderly SLE patients is necessary.

We herein report a case of otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) induced by propylthiouracil (PTU). A 30-year-old Japanese woman with Graves' disease, who was treated with PTU, reported with otitis media with sensorineural hearing loss bilaterally and trigeminal neuralgia on the left side, as well as elevated serum levels of myeloperoxidase-ANCA. Prior treatment with antibiotics was ineffective even after tympanostomy. However, clinical remission was immediately achieved after initiating prednisolone together with PTU withdrawal. These findings suggest that PTU therapy induces localized otological involvement as the concept of OMAAV.

We report the findings of an 18-year-old boy with immunoglobulin A vasculitis (IgAV) complicated with bowel perforation and nephritis. He presented with abdominal pain, arthralgia and palpable purpura. Massive proteinuria developed during his clinical course. The patient was treated successfully using combination therapy of glucocorticoid (GC), cyclosporine (CYA) and factor XIII (F XIII) replacement. A standard treatment strategy for severe IgAV patients has not been established due to its rarity. Combination therapy using GC, CYA and F XIII replacement should be considered for severe IgAV patients.

A 63-year-old woman presented with a fever, eruption, and sterile pyuria. A cystoscopic examination revealed submucosal nodular lesions in the trigone of the bladder, and a biopsy specimen showed epithelioid cell granulomas in the lamina propria of the bladder. Mycobacterium avium grew in the urine culture. Other organ involvement, such as the lungs, spleen, bones, muscles, and pelvic lymph nodes, was observed on radiological examinations, and M. avium was isolated from some organ lesions. Interferon-γ-neutralizing autoantibodies were detected in the patient's serum. Therefore, the patient was diagnosed with disseminated M. avium infection, which was resolved with antimycobacterial treatment.

Temozolomide, a key drug in the treatment of malignant glioma, can cause profound lymphopenia and various opportunistic infectious diseases. A 79-year-old woman with anaplastic oligodendroglioma developed a fever and gross hematuria after 8 weeks of standard radiotherapy with concomitant temozolomide treatment. A cytomegalovirus (CMV) antigen test for pp65 antigenemia was positive (137 cells per 75,800 leukocytes), and the findings from a urine cytology test were consistent with CMV-induced hemorrhagic cystitis. She was treated with ganciclovir, and her condition improved. CMV monitoring is needed when patients develop symptoms related to opportunistic infections during temozolomide treatment for malignant glioma.