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Low skeletal muscle, referred to as sarcopenia, has been shown to be an independent predictor of lower overall survival in various kinds of diseases. Several studies have evaluated the low skeletal muscle mass using computed tomography (CT) imaging. However, the cutoff values based on CT imaging remain undetermined in Asian populations. Preoperative plain CT imaging at the third lumbar vertebrae level was used to measure the psoas muscle mass index (PMI, cm2/m2) in 541 adult donors for living donor liver transplantation (LDLT). We analyzed PMI distribution according to sex or donor age, and determined the sex-specific cutoff values of PMI to define low skeletal muscle mass. PMI in men was significantly higher than observed in women (8.85 ± 1.61 cm2/m2 versus 5.77 ± 1.21 cm2/m2; P < 0.001). PMI was significantly lower in individuals ≥50 y than in younger donors in both men and women (P < 0.001 and P < 0.001, respectively). On the basis of the younger donor data, we determined the sex-specific cutoff values for the low skeletal muscle mass were 6.36 cm2/m2 for men and 3.92 cm2/m2 for women (mean − 2 SD). Data from healthy young Asian adults were used to establish new criteria for low skeletal muscle mass that would be applicable for defining sarcopenia in Asian populations. •Low muscle mass is an independent predictor of poor survival in various diseases.•We investigated the psoas muscle mass index (PMI) using computed tomography imaging in 541 healthy adults in Japan.•PMI was significantly lower in women and in individuals ≥50 y.•We established the sex-specific cutoff values of PMI to define low muscle mass.•This new criterion would be applicable for defining sarcopenia in Asia.

After graduation, he worked as a physician in the internal medicine department of Kobe University Hospital, Amagasaki Prefectural Hospital and Kitano Hospital for 4 years, during which time he became interested in the field of diabetes through encounters with Drs. Masaki Ikeda and Mikio Yawata. Fortunately, with the help of electrophysiologist Dr. Tohru Gonoi, we were able to combine molecular biology and electrophysiology, and succeeded in isolating Kir6.2 and determining the structure of β-cell ATP-sensitive potassium (KATP) channels as a complex of Kir6.2 and SUR1. [...]many patients with neonatal diabetes or congenital hyperinsulinemic hypoglycemia were found to have mutation of the Kir6.2 or SUR1 genes, and it became clear why sulfonylurea rather than insulin is effective in many cases of these diseases.

The dysfunction of pancreatic β-cells plays a central role in the onset and progression of type 2 diabetes mellitus (T2DM). Insulin secretory defects in β-cells are characterized by a selective impairment of glucose stimulation, and a reduction in glucose-induced ATP production, which is essential for insulin secretion. High glucose metabolism for insulin secretion generates reactive oxygen species (ROS) in mitochondria. In addition, the expression of antioxidant enzymes is very low in β-cells. Therefore, β-cells are easily exposed to oxidative stress. In islet studies using a nonobese T2DM animal model that exhibits selective impairment of glucose-induced insulin secretion (GSIS), quenching ROS generated by glucose stimulation and accumulated under glucose toxicity can improve impaired GSIS. Acute ROS generation and toxicity cause glucose metabolism disorders through different molecular mechanisms. Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor, is a master regulator of antioxidant defense and a potential therapeutic target in oxidative stress-related diseases, suggesting the possible involvement of Nrf2 in β-cell dysfunction caused by ROS. In this review, we describe the mechanisms of insulin secretory defects induced by oxidative stress in diabetic β-cells.

Wang et al. report that clinical dipeptidyl peptidase‐4 (DPP‐4) inhibitors show little effect on microbial DPP‐4 produced by Bacteroides genus. Furthermore, oral administration of microbial DPP‐4 to high‐fat diet‐fed mice was found to reduce plasma active glucagon‐like peptide‐1 levels through an increase in extraluminal intestinal tissular DPP‐4 activity, resulting in reduced glucose‐induced insulin levels and exacerbated glucose tolerance.

Leptin also suppresses neurons in the lateral hypothalamic area (LHA) that produce orexin and melanin-concentrating hormone, which stimulate eating behavior; and it activates POMC/CART neurons. Insulin receptors are expressed on the paraventricular nucleus (PVN), dorsomedial hypothalamus (DMH), and ARC, and intracerebral or hypothalamic insulin administration inhibits food intake by the suppression of NPY/AgRp neurons and the activation of POMC/CART neurons. [...]in the hypothalamus, pituitary gland, medulla oblongata, and other circumventricular organs, restriction by the BBB is weaker than that in the cerebral cortex, and intestinal hormones present in blood vessels thus have the potential to enter the brain 4.

Sarcopenia is characterized by muscle mass depletion and decrease in muscle power or physical activity. We previously reported that low skeletal muscle mass (SMM) is closely involved with posttransplant mortality in patients undergoing living donor liver transplantation (LDLT). The aim of this study was to prospectively investigate the effects of pretransplant sarcopenia on survival and examine sequential changes in sarcopenic parameters after LDLT. Sarcopenia was defined by measuring SMM using a multifrequency body composition analyzer and assessing grip strength (GS) in 72 adults who underwent LDLT at Kyoto University Hospital between January 2013 and October 2015. The effects of pretransplant sarcopenia on short-term survival and sequential changes in SMM and GS were prospectively analyzed. Of 72 patients, 10 (14%) were defined as having pretransplant sarcopenia. Overall survival rates were significantly lower in patients with sarcopenia (n = 10) than those without sarcopenia (n = 62; P < 0.001). SMM worsened after LDLT and did not return to preoperative levels until 1 y after LDLT. In contrast, GS returned to preoperative levels at 6 mo after LDLT, following sharp decrease at 1 mo after LDLT. This prospective study confirmed that pretransplant sarcopenia is closely associated with short-term survival after LDLT and that GS recovers before SMM. •Sarcopenia is characterized by muscle mass depletion and decrease in muscle power or physical activity.•We prospectively investigated the effects of pretransplant sarcopenia, defined as low skeletal muscle mass (SMM), using a multifrequency body composition analyzer and low grip strength on survival and examined sequential changes in sarcopenic parameters after living donor liver transplantation (LDLT).•Overall survival rates were significantly lower in patients with sarcopenia (n = 10) than those without sarcopenia (n = 62; P < 0.001).•Grip strength recovers earlier compared with SMM after LDLT.

Sarcopenia is an age-related disease with an increased risk of mortality. It is emerging that low serum 25-hydroxyvitamin D [25(OH)D] affects the sarcopenic state in general, but in rheumatoid arthritis (RA), these associations are not understood although the prevalence of vitamin D insufficiency is high in RA. We conducted a cross-sectional study of older female outpatients from our cohort (KURAMA) database. We measured skeletal muscle mass, handgrip strength, and gait-speed to diagnose severe sarcopenia. The serum 25(OH)D concentration was measured using electrochemiluminescence immunoassay. A total of 156 female patients with RA (sarcopenia:44.9%, severe sarcopenia: 29.5%, and without sarcopenia: 25.6%) were enrolled. Classification of vitamin D status at a cutoff point of median 25(OH)D concentration revealed that low 25(OH)D status was associated with a high prevalence of severe sarcopenia and with low measured values of muscle mass, handgrip, and gait speed. Furthermore, multivariable logistic regression analysis identified that low 25(OH)D status was associated with a high prevalence of severe sarcopenia (OR 6.00; 95% CI 1.99–18.08).The same association was observed when the cut-off value was set at 20 ng/ml. In components of sarcopenia, both low physical performance and muscle mass were associated with low 25(OH)D status. In conclusion, vitamin D status was inversely associated with severe sarcopenia, low physical performance, and low skeletal muscle mass. Modification of vitamin D status including vitamin D supplementation should be investigated as a therapeutic strategy for sarcopenic patients with RA.

Blocking the PD-1 pathway induces immune-related adverse events (irAEs) which often involve the thyroid gland (thyroid irAEs). Clinical features of a thyroid irAE including its predictability and relationship to prognosis remain to be elucidated. Two hundred consecutive patients treated with nivolumab at Kyoto University Hospital between September 1, 2014 and August 31, 2017 were included in a retrospective cohort study. We systematically determined and classified subclinical and overt thyroid irAEs based on data collected of serum free T4 and TSH levels. Baseline characteristics and detailed clinical data were analyzed, and analyses of overall survival (OS) excluded patients censored within 1 month from the first administration of nivolumab. Sixty-seven patients (33.5%) developed thyroid irAEs and these were divided into a subclinical thyroid irAE group (n = 40, 20.0%) and an overt thyroid irAE group (n = 27, 13.5%). Patients with thyroid uptake of FDG-PET before treatment showed high incidences of overt thyroid irAE (adjusted odds ratio 14.48; 95% confidence interval [CI] 3.12-67.19), while the same relationship was not seen with subclinical thyroid irAE. Regarding the total cohort, the thyroid irAE (+) group had a significantly longer median OS than the thyroid irAE (-) group (16.1 versus 13.6 months, hazard ratio [HR] 0.61; 95% CI 0.39-0.93). In 112 non-excluded patients with lung cancer, the thyroid irAE (+) group similarly had a longer median OS than the thyroid irAE (-) group (not reached versus 14.2 months, HR 0.51; 95% CI 0.27-0.92). However, this observation was not seen in 41 non-excluded patients with malignant melanoma (12.0 versus 18.3 months, HR 1.54; 95% CI 0.67-3.43). By thyroid uptake of FDG-PET, overt thyroid irAEs could be predicted before nivolumab therapy. Thyroid irAEs related to good prognosis in lung cancer but might be inconclusive in malignant melanoma.

BackgroundPreoperative loss of skeletal muscle mass, defined as sarcopenia, has been reported to be associated with higher incidence of complications following esophagectomy in patients with esophageal cancer. Although skeletal muscle loss promotes disability and reduced quality of life (QOL), only a few studies have focused on changes in skeletal muscle mass after surgery. This prospective cohort study aimed to evaluate the chronological changes in skeletal muscle mass after minimally invasive esophagectomy (MIE).MethodsPatients with esophageal cancer scheduled to undergo MIE at our institution were prospectively registered. Skeletal muscle mass was evaluated before and 2, 6, 12, and 24 months after surgery. The effects of preoperative sarcopenia on surgical outcomes and chronological changes in skeletal muscle mass were evaluated.ResultsAmong the 71 eligible preoperative patients, 29 (40.8%) were diagnosed with sarcopenia. Patients with sarcopenia had significantly higher incidences of total (79.3% vs 52.4%, p = 0.026) and gastrointestinal (37.9% vs 11.9%, p = 0.019) complications and a significantly longer length of hospital stay (31 vs 23 days, p = 0.005) than those without sarcopenia. The median skeletal muscle mass index (kg/m2) was 7.09 before surgery, which decreased to 6.46 two months after surgery (− 7.2%, P < 0.01). Thereafter, values of 6.90, 6.86, and 7.06 were reported at 6, 12, and 24 months after surgery, respectively.ConclusionPatients with preoperative sarcopenia developed more postoperative complications than those without it. Additionally, patients experienced a decrease in skeletal muscle mass during the early postoperative period following MIE. Further research on perioperative countermeasures to prevent skeletal muscle loss during the early postoperative period and to prevent postoperative complications is necessary for patients undergoing MIE.

Pancreas transplantation and islet transplantation are now established in the treatment of IDDM. Several trials of stem cell‐derived cell transplantation therapy are underway and may offer an alternative to the limited supply of donor islets in the near future. This article summarizes recent developments in transplantation therapy for diabetes as well as research on the use of stem cells for complications of diabetes.