Since the discovery of the K_ATP channel in 1983, numerous studies have revealed its physiological functions. The K_ATP channel is expressed in various organs, including the pancreas, brain and skeletal muscles. It functions as a "metabolic sensor" that converts the metabolic status to electrical activity. In pancreatic beta-cells, the K_ATP channel regulates the secretion of insulin by sensing a change in the blood glucose level and thus maintains glucose homeostasis. In 2004, heterozygous gain-of-function mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the K_ATP channel, were found to cause neonatal diabetes. In some mutations, diabetes is accompanied by severe neurological symptoms [developmental delay, epilepsy, neonatal diabetes (DEND) syndrome]. This review focuses on mutations of Kir6.2, the pore-forming subunit and sulfonylurea receptor (SUR) 1, the regulatory subunit of the K_ATP channel, which cause neonatal diabetes/DEND syndrome and also discusses the findings of the pathological mechanisms that are associated with neonatal diabetes, and its neurological features.

Objective Iron deficiency anemia (IDA) has become important with regard to mortality in hemodialysis (HD) patients. Therefore, it is necessary to optimize the treatment of these patients.

Methods IDA in end-stage renal disease patients on HD was observed in 42 (33.6%) of 125 patients. We examined the influence of daily orally iron [sodium ferrous citrate (SFC) iron/tablet 50 mg, 1-2 tablets] on the renal function markers, anemia and iron data for about 6 months.

Results The hematocrit and hemoglobin levels were significantly increased in the patients treated with SFC [hematocrit: before 28.5%±2.1% (mean ± standard deviation), 1st month 30.0%±2.3%, p<0.05; 3rd month 32.4%±2.9%, p<0.05; 6th month 31.3%±3.4%, p<0.05; and hemoglobin: before 9.25±0.70, 1st month 9.72±0.71, p<0.05; 3rd month 10.54±0.96, p<0.05; 6th month 10.25±1.21 g/dL, p<0.05]. The transferrin saturation (TSAT) and serum ferritin levels were significantly increased in the patients treated with SFC (TSAT: before 21.5%±10.0%, 1st-3rd month, 34.1%±15.1%, p<0.05; 6-8th month 34.7%±11.9%, p<0.05; and ferritin: before 38.2±37.1, 6-8th month 67.5±44.0 ng/mL, p<0.05). The present findings clearly indicate that oral iron is an effective route of iron supplementation in HD patients, and no adverse effects associated with SFC occurred during the treatment and follow-up period.

Conclusion Our results clearly indicate that oral iron delivered via SFC is a well-tolerated and effective form of iron supplementation in long-term HD and IDA patients in Japan.

Objective Among elderly patients with chronic obstructive pulmonary disease (COPD), there are some patients who cannot inhale tiotropium via Respimat^® due to poor hand-lung coordination. This study aimed to examine whether or not tiotropium inhalation therapy using Respimat^® with a spacer increased the forced expiratory volume in 1 s (FEV₁) in patients with COPD.

Methods A randomized, crossover, single-center study was conducted in 18 patients with stable COPD. Tiotropium (5 μg) via Respimat^® with or without a spacer (AeroChamber^®) was administered for 2 weeks. Following a 2-week washout period using a transdermal tulobuterol patch (2 mg per day), participants were then crossed over to the other inhalation therapy with respect to spacer use. The trough FEV₁ was measured at every visit using a spirometer. A questionnaire regarding inhalation therapy was administered to patients at the final visit.

Results The administration of tiotropium via Respimat^® both with and without a spacer significantly increased the trough FEV₁ from baseline during each treatment period, with mean differences of 115.0±169.6 mL and 92.8±128.1 mL, respectively. There was no significant difference in the change in the trough FEV₁ between the 2 procedures (p=0.66). A total of 86% of patients reported that inhalation using a spacer was not difficult, and more than half also rated both the usage and maintenance of the AeroChamber^® as easy.

Conclusion Tiotropium inhalation therapy administered via Respimat^® using a spacer exerted a bronchodilatory effect similar to that observed with tiotropium Respimat^® alone.

Objective We retrospectively compared the clinical efficacy and toxicity of rituximab (R)-THP-COP (pirarubicin, cyclophosphamide, vincristine, and prednisolone) with that of R-CHOP (rituximab, adriamicin, cyclophosphamide, vincristine, and prednisolone) in previously untreated old patients with diffuse large B-cell lymphoma (DLBCL).

Patients and Methods Patients admitted to our institution between 2004 and 2013 were examined. The patients received either R (375 mg/m², day 1)-THP-COP (pirarubicin 50 mg/m² day 1, cyclophosphamide 750 mg/m² day 1, vincristine 1.4 mg/m² day 1, and prednisolone 100 mg day 1-5) or R-CHOP (adriamicin 50 mg/m² day 1, cyclophosphamide 750 mg/m² day 1, vincristine 1.4 mg/m² day 1, and prednisolone 100 mg day 1-5). The doses of chemotherapeutic agents were adjusted depending on the patient's age and associated complications. The treatment was performed for 6 to 8 cycles.

Results Among 74 patients with DLBCL (median 76, range 65-90 years; male 39, female 35), 29 received R-THP-COP, while 45 received R-CHOP. The overall response rates were 94.6% (complete response 86.4%, partial response 8.1%). The 2-year overall and progression-free survival rates were 77.6% and 68.5% for the R-THP-COP regimen and 79.2% and 78.9% for R-CHOP, respectively. No significant differences were found between these two regimens regarding the clinical efficacies. The most frequent adverse event was neutropenia (72.4% for the R-THP-COP regimen, 88.9% for the R-CHOP regimen). The cardiac function as evaluated by ejection fraction values was not impaired in either regimen.

Conclusion R-THP-COP was effective and safe as an alternative to R-CHOP.

Objective To examine whether or not an edrophonium challenge test is useful for diagnosing cervical dystonia.

Patients We evaluated 10 patients with cervical dystonia and 10 with hemifacial spasms (disease controls). We administered edrophonium and saline in this double-blinded study. Before and after the injection, we recorded the participants' clinical signs using a video camera to assess the objective symptoms every two minutes. Ten minutes after the saline and edrophonium injections, participants evaluated their subjective clinical signs using a visual analog scale. The objective signs on the video recordings were scored by specialists who were blinded to the treatment. The mean visual analog scale scores were compared using the Wilcoxon rank-sum test for paired continuous variables.

Results The clinical signs of participants with cervical dystonia were amplified by edrophonium. In contrast, the clinical signs in participants with hemifacial spasms were not affected by the edrophonium challenge test.

Conclusion The edrophonium challenge test may be useful for diagnosing cervical dystonia.

Objective Dietary salt reduction is important for the prevention and treatment of lifestyle-related diseases, including hypertension. Thus, in order to follow a strict low-salt diet, it is necessary to assess one's salt intake and to become aware of the importance of salt reduction.

Methods More than 2,000 employees of a company, who received a periodic health checkup, participated in the present study. They assessed their day-to-day diet-related lifestyle, using the Salt Check Sheet, and we analyzed the correlations among the Salt Check Sheet scores, the daily salt intake (as estimated by a spot urine sample), and the results of the periodic health checkup.

Results In the overall survey population, we only found a weak correlation between the salt check scores and the salt intake. In a subgroup analysis, significant correlations between these two variables were observed among untreated hypertensive participants, but not among treated hypertensive participants. We examined the association between 13 individual questionnaire items and the estimated daily salt intake using a multivariate linear regression model and found that only 5 of the 13 questionnaire items were correlated with the daily salt intake.

Conclusion We found that a Salt Check Sheet composed of the 5 items that showed a strong correlation with the salt intake might be more useful for periodic health checks of the working-age population.

A 67-year-old woman with recurrent gastrointestinal bleeding and aortic valve stenosis presented with spurting bleeding from angiodysplasia of the upper jejunum. As electrophoresis revealed decreased levels of high-molecular-weight (HMW) von Willebrand factor (VWF) multimers, she was diagnosed with Heyde's syndrome. After aortic valve replacement, her HMW VWF levels quickly recovered to normal, and the gastrointestinal bleeding ceased. However, capsule endoscopy still revealed gastrointestinal angiodysplasia six months later. This case shows that minute analyses of VWF multimers enable the diagnosis and confirmation of the resolution of Heyde's syndrome, and implies that gastrointestinal angiodysplasia can be attributed to unknown factors other than decreased VWF multimers.

Although improved treatments for acute myocardial infarction (AMI) have considerably reduced the mortality of AMI in the past two decades, the treatment for ventricular septal rupture (VSR)-a rare but life-threatening mechanical complication of AMI-still remains quite challenging. We herein describe the case of a high-surgical-risk patient with VSR after AMI who was successfully treated using tolvaptan (a novel V₂-receptor antagonist) without any mechanical support.

A 70-year-old man, who had undergone the placement of an endovascular aneurysm repair graft for an abdominal aortic aneurysm 7 years previously, presented to our facility with the separation of a left iliac stent-graft limb from the main-body stent-graft, resulting in a type III endoleak. An attempt was made to repair the disconnected stent-graft limb with endovascular intervention. An extension stent-graft was successfully deployed using a pulled-through technique to connect the main-body stent-graft with the disconnected stent-graft limb. Endovascular intervention may be an acceptable treatment for type III endoleaks.

Immunoglobulin G4 (IgG4)-related disease is a systemic inflammatory disorder that was first described in patients with autoimmune pancreatitis. Although IgG4-related disease is thought to involve the cardiovascular system, case reports describing coronary artery involvement are relatively rare. We describe a patient who was previously diagnosed with autoimmune pancreatitis and found to have coronary periarteritis and luminal narrowing. After the initiation of steroid treatment, the patient's coronary periarteritis and luminal stenosis were both ameliorated with an improvement in the serum IgG4 concentration. The present findings collectively suggest that IgG4-related immuno-inflammation may have a role in the development of coronary periarteritis and luminal atherosclerosis.

We herein report the clinical course of a patient who had a good neurological outcome despite severe anemia, high serum lactate levels, and a long period of time from cardiac arrest (CA) to extracorporeal cardio-pulmonary resuscitation (ECPR) establishment. During the period of resuscitation, the tissue oxygenation index (TOI) values were measured continuously by a near-infrared spectroscopy monitoring device and were kept within the normal range. The TOI seems to reflect cerebral perfusion and the balance between the oxygen supply and demand in the brain during ECPR, thereby predicting the neurological outcome. Continuous TOI monitoring is useful for predicting the neurological outcome during ECPR.

Acromegaly is caused by excessive growth hormone secretion, usually from pituitary adenomas. Somoatostatin analogues are widely used as primary or adjunctive therapy in the management of acromegaly. In this report, we present a case with remarkable shrinkage of a tumor after relatively short-term octreotide long-acting release (LAR) administration. During the 30-month follow-up after starting octreotide LAR, there was no recurrence of acromegaly with remarkable shrinkage of the tumor on pituitary magnetic resonance imaging. A literature review of the predictors for tumor shrinkage after the administration of somatostatin analogues in patients with acromegaly is also discussed in relation to this case.

Nivolumab has promising efficacy for treating various advanced malignant tumors, although it has been reported to induce a wide range of autoimmune adverse effects. We herein report the case of a patient with metastatic lung adenocarcinoma who developed adrenal insufficiency after 12 cycles of nivolumab treatment. Endocrine test results supported a diagnosis of isolated adrenocorticotropic hormone deficiency due to hypophysitis, and replacement therapy using hydrocortisone has been successful. Although hypophysitis is a rare immune-related adverse event that is associated with nivolumab therapy, clinical awareness is essential, as this condition can be life-threatening and requires prompt treatment.

A 78-year-old man presented with cutaneous blisters of the limbs and abdominal distension. He had been treated for various diseases, including liver cirrhosis. He had begun receiving sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, for diabetes mellitus three years before the hospitalization. A skin biopsy demonstrated bullous pemphigoid. Ultrasonography (US) revealed multiple liver tumors, although he had been receiving regular US studies. We stopped sitagliptin and started insulin and corticosteroids. However, his renal dysfunction progressed, and he died 14 days after the hospitalization. We should therefore be careful of various complications, including bullous pemphigoid and progression of tumors, when using DPP-4 inhibitors.

Patients with anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM GN) have severe kidney dysfunction, leading to end-stage renal disease. The effect of plasmapheresis and immunosuppressive treatment in patients with severe glomerular changes is controversial. A 62-year-old man was admitted with rapidly progressive glomerulonephritis and diagnosed with anti-GBM GN. He required hemodialysis. All glomeruli in the kidney biopsy specimen had cellular crescents without fibrotic changes, suggesting reversible damage. He was treated with plasmapheresis until the anti-glomerular basement membrane antibodies disappeared. His kidney function recovered, and dialysis was able to be discontinued. Frequent plasmapheresis in patients with dialysis-dependent anti-GBM GN may improve the kidney prognosis.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) has a curative potential for myelofibrosis (MF) patients; however, its association with a high therapy-related mortality (TRM) remains a big obstacle that needs to be overcome. Ruxolitinib (RUXO), a novel JAK1/2 inhibitor, can be used as a bridging therapy until allo-SCT can be performed to reduce TRM. We herein report a RUXO-treated MF patient who developed recurrent subcutaneous Sweet's disease (SSD) that was successfully treated by the administration of systemic glucocorticoids. We performed allo-SCT as previously scheduled, resulting in a good clinical course without deterioration of SSD. RUXO administration, as well as MF itself, might therefore sometimes cause this rare non-infectious event.

A 65-year-old man was diagnosed with polycythemia vera (PV) and treated with hydroxyurea. Three years later, he was admitted to our institution for severe hypoxia. Right heart catheterization revealed that the patient had pulmonary hypertension (PH). In addition, radiographic findings and resistance to pulmonary vasodilators led to the diagnosis of PH associated with pulmonary veno-occlusive disease. The administration of ruxolitinib improved his hematopoiesis and respiratory failure. While the disease is relatively common in Europe and the United States, limited data exist regarding myeloproliferative neoplasm complicated with PH in Japan. PH should be considered a potential complication and screened during the clinical care of patients with myeloproliferative neoplasms.

Transfusion-related acute lung injury (TRALI) is defined as a new episode of acute lung injury (ALI) occurring during transfusion or within 6 hours of transfusion completion. A 66-year-old man suffering from acute myeloid leukemia developed acute respiratory distress syndrome after platelet transfusion. TRALI was diagnosed clinically, but an autopsy showed leukemic cells in diffuse pulmonary edema. Anti-human neutrophil antigen (HNA)-3a antibodies were detected in the donor serum, and the HNA-3 genotype of the patient was identified as a/a. This case was considered to represent pulmonary involvement of acute myeloid leukemia, rather than TRALI. A revision of the definition of TRALI accounting for hematological malignancies should therefore be considered.

A 49-year-old man presented with gradually progressive aphasia one month after being diagnosed with acquired immunodeficiency syndrome (AIDS). Brain magnetic resonance imaging showed multiple brain lesions with punctate and linear enhancement. A polymerase chain reaction detected Epstein-Barr virus (EBV) in the patient's cerebrospinal fluid. A diagnosis of isolated central nervous system lymphomatoid granulomatosis (CNS-LYG) was made based on the brain biopsy findings. The complete remission of CNS-LYG was achieved by anti-retroviral therapy (ART) alone. In the present case, the development of AIDS-associated CNS-LYG was considered to have been initiated by the reactivation of EBV in the CNS under immunosuppressive conditions. The patient's condition improved with the reconstitution of the patient's immune system.

Ataxic hemiparesis (AH) is a classic lacunar syndrome associated with localized damage to the pons, internal capsule, thalamus, or corona radiata. A depression of metabolic activity known as crossed cerebellar diaschisis (CCD) is frequently observed in the cerebellar hemisphere contralateral to the site of the lesion in patients with AH. Though small cortical or subcortical lesions may result in AH, such occurrences are rare. The current report details the case of a patient with AH resulting from acute infarction associated with localized lesions of the postcentral gyrus who presented without CCD.

We herein report the case of a 47-year-old female with the colony-stimulating factor 1 receptor (CSF1R) mutation p.G589R, which is related to hereditary leukoencephalopathy with axonal spheroid (HDLS). The patient presented with an early-onset cognitive decline and progressive aphasia. Brain magnetic resonance imaging revealed HDLS-related alterations. In addition, brain computed tomography revealed interspersed spotty calcifications in the frontal and parietal subcortical white matter, while a characteristic "stepping stone" appearance was observed in the frontal pericallosal regions. Our findings emphasize the importance of calcification appearances in establishing an HDLS diagnosis and in screening for CSF1R mutations.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory central nervous system disorder that mainly involves in the brainstem, basal ganglia and cerebellum. We herein report the case of a patient with CLIPPERS, which was diagnosed based on the clinical and radiological features. After initially responded to steroid treatment, the patient developed limbic encephalitis. The patient presented with memory disturbance, a delirious state and emotional incontinence. A cerebrospinal fluid study revealed interleukin-6 elevation and enhanced bilateral hippocampal lesions were observed on MRI. The patient was successfully treated with methylprednisolone pulse therapy. This is the first case of CLIPPERS with limbic encephalitis involving the bilateral hippocampus.

A 69-year-old woman was admitted to our hospital with the chief complaints of fever and fatigue. We initially treated the patient for a tick-borne disease after noticing a pustule on her leg; however, abdominal computed tomography (CT) showed multiple low-density areas in the liver and Chromobacterium violaceum was isolated from a blood culture. We diagnosed her with multiple liver abscesses secondary to Chromobacterium violaceum bacteremia. The patient was successfully treated with ciprofloxacin.

We herein report the case of a 66-year-old woman presenting with symptoms of gastroenteritis. Computed tomography showed small-bowel dilation without ischemic signs. After admission, she went into shock and was treated for sepsis of unknown origin. She was later diagnosed with group A streptococcal peritonitis due to an ascending vaginal infection. This case highlights the importance of considering Group A Streptococcus (GAS) infection as a cause of peritonitis in postmenopausal women.