Sleep-disordered breathing (SDB) is a risk factor for cardiovascular disease including acute coronary syndrome and acute myocardial infarction, and treating SDB prevents their development and recurrence and improves a patient's prognosis. Therefore, SDB is considered a therapeutic target for cardiovascular disease. In 2010, the Japanese Circulation Society published guidelines for the diagnosis and treatment of SDB in patients with cardiovascular disease. However, therapeutic intervention for patients with SDB was recently reported not to suppress the development or deterioration of cardiovascular disease in three middle- to large-sized randomized clinical trials: the SERVE-HF trial, which examined the effects of adaptive servo-ventilation (ASV) on patients with chronic heart failure (CHF) and central sleep apnea; the CAT-HF trial, which examined the effects of ASV therapy on patients with CHF after acute deterioration; and the SAVE study, which examined the secondary preventive effect of continuous positive airway pressure (CPAP) on patients with ischemic heart disease who had mild to moderate obstructive sleep apnea. These studies caused hesitation among clinicians to proactively treat SDB by ASV or CPAP therapy. The present review is focused on hypertension, pulmonary hypertension, ischemic heart disease, and CHF to newly summarize the studies available to date from the viewpoints of epidemiology, pathogenesis, and treatment. I expect this review be informative and useful for physicians who treat patients with SDB by CPAP or ASV therapy in the clinical setting.

Background/Aim: Epigenetic inactivation of tumor suppressor genes is an important molecular mechanism in the formation and development of human tumors. The purpose of our study was to evaluate the correlation between the methylation level of the secreted frizzled-related protein 1 (SFRP1) gene and the risk of renal cell carcinoma (RCC). Methods: The relevant literature was searched in detail in several electronic databases. The methodological heterogeneity was analyzed by meta-regression and subgroup analyses. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to summarize the dichotomous outcomes of our meta-analysis. Results: The ten included articles contained 535 RCC samples and 475 normal controls. The results demonstrated that the methylation level of the SFRP1 promoter region was significantly correlated with an increased incidence of RCC (OR=13.72; 95% CI: 6.01-31.28; P=0.000). Furthermore, the eligible studies that had sufficient clinical data about the RCC cases were included in the analysis, and the results indicated that the frequency of SFRP1 promoter methylation was associated with a higher histological grade (P=0.000), tumor stage (P=0.033), tumor size (≥5 cm; P=0.029), and distant metastasis (P=0.047). Conclusion: Our results indicate that the methylation level of the SFRP1 promoter region is increased in patients with RCC compared to normal controls and might be involved in the occurrence and development of RCC. Additional well-designed studies are needed to further verify our conclusions.

Idiopathic ventricular premature contractions (VPCs), defined as VPCs in the absence of obvious structural heart disease, are one of the common types of arrhythmia in clinical practice. They are sometimes complicated with non-sustained ventricular tachycardia (VT), and/or sustained VT with almost same QRS morphology in 12 leads ECG. Idiopathic VT (IVT) commonly occurs by focal mechanisms and the origins are distributed in a variety of sites in both ventricles. In this article, the clinical characteristics of IVT/IVPCs, the diagnostic algorithm, and how to ablate them will be reviewed.

Background: The antidiabetic drug teneligliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor with a thiazolidine-specific structure. This study aimed to investigate whether teneligliptin can activate PPARγ directly and/or indirectly in cell-based assays. Methods: Promoter assays using the reporter construct driven under the control of the SV40 promoter and the PPAR response element (PPRE) were performed. Luciferase activity was measured after a 3-day incubation of vector-transduced cells with various concentrations of teneligliptin. Results: Treatment of the cells with 50 μM teneligliptin significantly transactivated a reporter gene. The presence of the PPARγ antagonist, GW9662, did not affect the activation of PPRE-reporter expression by teneligliptin. Conclusion: We found that teneligliptin could increase PPARγ activity in cell-based assays irrespective of the PPARγ ligand-binding domain.

Introduction: Various innovations for preventing complications and improving a patient's quality of life have been implemented for peritoneal dialysis (PD), which was established in Japan approximately 35 years ago and introduced at our hospital in 1999. Herein, we investigate the outcomes of patients undergoing PD to identify approaches for improving their long-term prognosis. Methods: This retrospective study included 114 patients who underwent PD between September 1999 and August 2017 and included various parameters such as patient survival rate, technical survival rate, cause (s) of PD withdrawal, incidence of peritonitis, dialysis duration, and change in residual renal function (RRF). Furthermore, factors associated with PD withdrawal and duration, as well as risk factors for peritonitis, were examined. Results: Mean (± standard deviation) PD duration was 35.62 (±29.88) months in all patients and 37.16 (±34.09) months in 58 patients who withdrew from treatment. Five-year continuance and survival rates were 40.41% and 55.74%, respectively (p=0.0061). However, in patients aged ≥65 years, the continuance and survival rates were not significantly different (p=0.1250). Furthermore, the continuance and survival rates in diabetic patients were not significantly different from those of non-diabetic patients (p=0.1334 and 0.7140, respectively). Comparison of changes in RRF in young and elderly patients revealed that it was not significantly sustained in elderly patients (p=0.0259). The Cox proportional hazards model revealed that age (p=0.0455) and total cholesterol levels (p=0.0494) were independent risk factors for PD withdrawal, and multiple regression analysis showed that the presence of peritonitis (p=0.0063) and low-density lipoprotein cholesterol (LDL-C) levels (p=0.0087) were significant factors for PD duration. Peritonitis incidence was 0.077 times per patient per year, and multivariate analysis identified PD duration (p=0.0009) and LDL-C levels (p=0.0054) as independent risk factors for peritonitis. Conclusion: The findings of this study revealed that assessment of the nutritional status of the patient and prevention of peritonitis are important for continuation of PD. PD is a safe treatment option that can maintain the quality of life in elderly patients. In a rapidly aging society, the need for PD-based medical care is expected to increase.

Background: Photoreceptors differentiated from somatic cells are a useful tool for transplantation and drug screening. We previously showed that photosensitive cells are differentiated from human fibroblasts by direct reprogramming. In induced pluripotent stem (iPS) cells or embryonic stem (ES) cells, the properties of differentiated cells differ among the source of cell lines. However, whether or not the properties of the photosensitive cells produced by direct reprogramming are controlled by the origin of the cell line remains unknown. Methods: We compared the morphological and physiological properties of photosensitive cells induced by two fibroblast cell lines. Results: The differentiated cells had larger somas and more primary processes than the non-infected cells in both cell lines. The degree of morphological change was statistically different between the two cell lines. In addition, physiological responses to light differed between the two cell lines. An outward current (photoreceptor-like response) was observed in both cell lines, while an inward current (intrinsically photosensitive retinal ganglion cell-like response) was observed only in one cell line under light stimulation. Conclusions: These results suggest that photosensitive cells produced from different cell lines by direct reprogramming might express different phenotypes.

A 61-year-old woman was admitted to our hospital because of muscle paralysis and was found to have severe hypokalemia. A gallium-67 scintigram revealed a positive accumulation in the bilateral salivary glands, and a labial minor salivary gland biopsy demonstrated a massive lymphocyte infiltrate around the salivary ducts. She was diagnosed with Sjögren's syndrome (SS) associated with renal tubular acidosis. Renal biopsy revealed tubulointerstitial nephritis with a mild focal infiltration of lymphocytes and plasma cells. These pathological features were compatible with SS with renal involvement. Acidosis and hypokalemia were corrected with sodium bicarbonate and potassium chloride, which relieved the patient's symptoms. Although steroid therapy has been reported to be effective in SS-associated tubulointerstitial nephritis, the patient's serum potassium level could be controlled without administering steroids during the first admission. Five years later, she was admitted again because of severe liver dysfunction attributed to autoimmune hepatitis. Oral administration of prednisolone resulted in the normalization of her transaminase levels, and the control of her serum potassium level became easier. It has been reported that patients with SS with salivary gland involvement tend to have hepatic complications, and those with hepatic complications tend to have renal involvement. Physicians should be aware of hepatic involvement, even if there is no liver dysfunction at the initial diagnosis of SS with salivary gland and renal involvement. It remains uncertain whether the administration of a low dose of steroids before the onset of autoimmune hepatitis might have prevented the development of liver dysfunction in our patient.

More than 6,000 people died in the Great Hanshin (Kobe) Earthquake in 1995, and it was later reported that there were around 500 preventable trauma deaths. In response, the Japanese government developed the helicopter emergency medical service in 2001, known in Japan as the "Doctor-Heli" (DH), which had 46 DHs and 2 private medical helicopters as of April 2016. DHs transport physicians and nurses to provide pre-hospital medical care at the scene of medical emergencies. Following lessons learned in the Great East Japan Earthquake in 2011, a research group in the Ministry of Health, Labour and Welfare developed a command and control system for the DH fleet as well as the Disaster Relief Aircraft Management System Network (D-NET), which uses a satellite communications network to monitor the location of the fleet and weather in real-time during disasters. During the Kumamoto Earthquake disaster in April 2016, 75 patients were transported by 13 DHs and 1 private medical helicopter in the first 5 days. When medical demand for the DHs exceeded supply, 5 patients, 8 patients, and 1 patient were transported by Self-Defense Force, Fire Department, and Coast Guard helicopters, respectively. Of the 89 patients who were transported, 30 (34%) had trauma, 3 (3%) had pulmonary embolisms caused by sleeping in vehicles, and 17 (19%) were pregnant women or newborns. This was the first time that the command and control system for aeromedical transport and D-NET, established after the Great East Japan Earthquake in 2011, were operated in an actual large-scale disaster. Aeromedical transport by DHs and helicopters belonging to several other organizations was accomplished smoothly because the commanders of the involved organizations could communicate directly with each other in person within the Aviation Coordination Section of the prefectural government office. However, ongoing challenges in the detailed operating methods for aeromedical transport were highlighted and include improving shared knowledge and training across the organizational framework. These are particularly important issues to address given the Nankai Trough and Tokyo inland earthquakes that are predicted for the near future in Japan.

We report on two siblings with early onset lysosomal acid lipase deficiency or Wolman disease. Their parents had a consanguineous marriage. The children showed evidence of abdominal distension and failed to thrive, despite having regular nutrition. At 3-4 months of age, their abdominal distension and jaundice progressed rapidly and they died of liver failure. Sebelipase alfa, a recombinant form of human lysosomal acid lipase has recently been used as an enzyme replacement therapy in patients with later-onset cholesteryl ester storage disease. Therefore, we investigated cases of lysosomal acid lipase deficiency in Japan and found that the number of cases was extremely low. Only 14 cases of Wolman disease and seven cases of cholesteryl ester storage disease were reported. As it is now possible to treat lysosomal acid lipase deficiency, it is important to increase awareness of this disease among pediatricians and doctors working in internal medicine.

We report here a case of systemic lupus erythematosus (SLE) with pulmonary hemorrhage and anti-glomerular basement membrane (anti-GBM) antibodies. A 42-year-old woman was admitted to our hospital with complaints of exanthema, arthralgia, shortness of breath, and hemoptysis. Plain chest computed tomography (CT) scan revealed pericardial effusion, bilateral pleural effusions, and pulmonary hemorrhage. Laboratory findings on admission revealed proteinuria, microscopic hematuria, anemia, leukopenia, hypoalbuminemia, hypocomplementemia, and slightly elevated levels of serum creatinine. Serological tests revealed elevated titers of serum anti-GBM antibodies, proteinase 3-antineutrophil cytoplasmic antibodies (PR3-ANCA), and anti-double stranded deoxyribonucleic acid (dsDNA)-immunoglobulin G (IgG) antibodies. Early treatment with steroid pulse therapy combined with plasma exchange resolved the patient's pulmonary hemorrhage and renal dysfunction. Renal biopsy carried out after the treatment revealed a recovery phase of acute tubular injury with minor glomerular abnormalities without linear IgG deposition along the GBMs. For a good prognosis, it is necessary to start treatment immediately in patients with anti-GBM antibody-positive SLE associated with pulmonary hemorrhage.