Follow-up strategies for patients with gastrointestinal stromal tumour treated with or without adjuvant imatinib after surgery

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低インスリン血症は、非糖尿病急性非代償性心不全患者において、全死亡、心血管死の独立した予後予測因子である

Background Insulin beneficially affects myocardial functions during myocardial ischemia. It increases glucose-derived ATP production, decreases oxygen consumption, suppresses apoptosis of cardiomyocytes, and promotes the survival of cardiomyocytes. Patients with chronic heart failure generally have high insulin resistance, which is correlated with poor outcomes. The role of insulin in acute decompensated heart failure (ADHF) remains unclear. This study aimed to investigate the prognostic value of serum insulin level at the time of admission for long-term outcomes in patients with ADHF. Methods and Results We enrolled 1074 consecutive patients who were admitted to our department for ADHF. Of these 1074 patients, we studied the impact of insulin on the prognosis of ADHF in 241 patients without diabetes mellitus. The patients were divided into groups according to low, intermediate, and high tertiles of serum insulin levels. Primary end points were all-cause death and cardiovascular death. During a mean follow-up of 21.8 months, 71 all-cause deaths and 38 cardiovascular deaths occurred. Kaplan-Meier analysis showed that all-cause and cardiovascular mortality was significantly higher in the low-insulin group than those in the intermediate- and high-insulin groups (log-rank P=0.0046 and P=0.038, respectively). Moreover, according to the multivariable analysis, low serum insulin was an independent predictor of all-cause and cardiovascular mortality (hazard ratio, 2.37 [95% CI, 1.24-4.65; P=0.009] and 2.94 [95% CI, 1.12-8.19; P=0.028], respectively). Conclusions Low serum insulin levels were associated with increased risk of all-cause and cardiovascular death in ADHF patients without diabetes mellitus.博士（医学）・甲第808号・令和4年3月15日© 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License(https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes

日本における非代償性急性心不全患者の30日および90日以内の心不全再入院の発生率と臨床的意義 : NARA-HF研究より

Background: Countermeasure development for early rehospitalization for heart failure (re-HHF) is an urgent and important issue in Western countries and Japan.Methods and Results:Of 1,074 consecutive NARA-HF study participants with acute decompensated HF admitted to hospital as an emergency between January 2007 and December 2016, we excluded 291 without follow-up data, who died in hospital, or who had previous HF-related hospitalizations, leaving 783 in the analysis. During the median follow-up period of 895 days, 241 patients were re-admitted for HF. The incidence of re-HHF was the highest within the first 30 days of discharge (3.3% [26 patients]) and remained high until 90 days, after which it decreased sharply. Within 90 days of discharge, 63 (8.0%) patients were re-admitted. Kaplan-Meier analysis revealed that patients with 90-day re-HHF had worse prognoses than those without 90-day re-HHF in terms of all-cause death (hazard ratio [HR] 2.321, 95% confidence interval [CI] 1.654-3.174; P<0.001) and cardiovascular death (HR 3.396, 95% CI 2.153-5.145; P<0.001). Multivariate analysis indicated that only male sex was an independent predictor of 90-day re-HHF. Conclusions: The incidence of early re-HHF was lower in Japan than in Western countries. Its predictors are not related to the clinical factors of HF, indicating that a new comprehensive approach might be needed to prevent early re-HHF.博士（医学）・甲第735号・令和2年3月16日日本循環器学会の許諾を得て登録（2020年9月2日付）ジャーナル公式サイト（日本循環器学会HP内）：https://www.j-circ.or.jp/journal/公開サイト（J-STAGE）：https://www.jstage.jst.go.jp/browse/circj

急性心不全における退院時の尿素窒素分画排泄率の予後判定への有用性

Background Maintaining euvolemia is crucial for improving prognosis in acute decompensated heart failure (ADHF). Although fractional excretion of urea nitrogen (FEUN) is used as a body fluid volume index in patients with acute kidney injury, the clinical impact of FEUN in patients with ADHF remains unclear. This study aimed to investigate whether FEUN can determine the long-term prognosis in patients with ADHF. Methods and Results We retrospectively identified 466 patients with ADHF who had FEUN measured at discharge between April 2011 and December 2018. The primary endpoint was post-discharge all-cause death. Patients were divided into two groups according to a FEUN cut-off value of 35%, commonly used in pre-renal failure. The FEUN <35% (low-FEUN) group included 224 patients (48.1%), and the all-cause mortality rate for the total cohort was 37.1%. The log-rank test revealed that the low-FEUN group had a significantly higher rate of all-cause death compared to the FEUN equal to or greater than 35% (high-FEUN) group (P<0.001). Multivariate Cox proportional hazards model analysis revealed that low-FEUN was associated with post-discharge all-cause death, independently of other heart failure risk factors (hazard ratio, 1.467; 95% CI, 1.030-2.088, P=0.033). The risk of low-FEUN compared to high-FEUN in post-discharge all-cause death was consistent across all subgroups; however, the effects tended to be modified by renal function (threshold: 60 mL/min/1.73 m2, interaction P=0.069). Conclusions Our study suggests that FEUN may be a novel surrogate marker of volume status in patients with ADHF requiring diuretics.博士（医学）・甲第814号・令和4年3月15日Copyright © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License(https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made

僧帽弁閉鎖不全症を伴うまたは伴わない非代償性急性心不全患者の予後に心房細動が与える影響

Background: Atrial fibrillation (AF) and mitral regurgitation (MR) are frequently combined in patients with heart failure (HF). However, the effect of AF on the prognosis of patients with HF and MR remains unknown. Methods and Results: We studied 867 patients (mean age 73 years; 42.7% female) with acute decompensated HF (ADHF) in the NARA-HF registry. Patients were divided into 4 groups based on the presence or absence of AF and MR at discharge. Patients with severe MR were excluded. The primary endpoint was the composite of cardiovascular (CV) death and HF-related readmission. During the median follow-up of 621 days, 398 patients (45.9%) reached the primary endpoint. In patients with MR, AF was associated with a higher incidence of the primary endpoint regardless of left ventricular function; however, in patients without MR, AF was not associated with CV events. Cox multivariate analyses showed that the incidence of CV events was significantly higher in patients with AF and MR than in patients with MR but without AF (hazard ratio 1.381, P=0.036). Similar findings were obtained in subgroup analysis of patients with AF and only mild MR. Conclusions: The present study demonstrated that AF is associated with poor prognosis in patients with ADHF with mild to moderate MR, but not in those without MR.博士（医学）・甲第799号・令和3年9月29日© 2021, THE JAPANESE CIRCULATION SOCIETY This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license. https://creativecommons.org/licenses/by-nc-nd/4.0

コウガクブ ノ ガクセイ ニ オケル サイショウ エイゴ テスト:2014ネン ダイガク ニュウシ センター シケン(エイゴ) ト ノ ソウカン カンケイ

牧グループは,日本人大学生の英語能力を測定するために,CD を聞きながら,問題用紙の空欄に英単語を埋めていく,簡易型(時間短縮系)英語能力測定試験としての5分間の最小英語テスト(Minimal English Test, MET)を開発した。本研究では,工学部の学生において,6単語毎(5単語置き)に空欄を設けた,6単語毎版(5単語置き版)最小英語テスト(Minimal English Test 6B, MET 6B)を実施し,MET6Bの得点と,大学入試センター試験(2014年)の英語の得点の間に,統計的有意な相関があるかどうかを調査した。回帰分析の結果,(1)工学部の学生に関して,MET 6Bは,大学入試センターの英語試験における読解力だけを予測するものではなく,読解力と聴解力を合わせた英語総合得点を予測するものであること,(2)これまで牧グループが,様々な学部の学生を対象に行ってきたMET6A/6B調査における,MET6A/6B得点と大学入試センター試験の英語総合点との間の相関係数に比べ(.53<r<.61),工学部の学生のみにおける,その両テストの得点間の相関係数がはるかに低かった(r=.43)ことを報告する。そして,工学部の学生に対しては,現在のMET 6Bバージョンが,大学入試センターの英語試験で測定される英語能力を正確に予測していないことから,そこに働いている要因を解明し,更なる適切なMETのバージョンを開発する必要があることを示唆する。Maki, Wasada, and Hashimoto (2003) developed the Minimal English Test (MET), a 5-minute English test, which requires the test taker to write a correct English word with 4 letters or fewer into each of the 72 blank spaces of the given sentences while listening to the CD. Revising the original MET, the Maki group created the MET 6A/6B, where every 6th word was a target word. The MET 6A and the MET 6B only differ in the position of the first target word. Their past surveys include the English learners of a variety of majors. In this research we investigated whether the MET 6B can correctly measure English proficiency of university freshmen who major in a particular academic field, such as engineering. We examined the correlations between the scores on the MET 6B and the scores on the English Part of the University Entrance Examinations administered by the National Center for University Entrance Examination in Japan. We call the University Entrance Examination (English Part) the Center Test (CT) in this paper. Our findings are as follows: First, for the engineering majors, the MET 6B does not simply predict the scores on the Reading Section of the CT 2014, but rather predicts the total scores on the CT 2014. Second, the correlation coefficient between the scores on the MET 6B and the total scores on the CT 2014 with respect to the engineering majors (r=.43) is far lower than the results of the Maki Group\u27s past surveys from 2009 to 2014, in which the correlation coefficients between the scores on the MET 6A/6B and the total scores on the CTs are more or less consistent (from .53 to .61). This seems to indicate that the current version of the MET 6B does not precisely predict English proficiency of engineering majors, in terms of the total scores on the CT. This in turn suggests that there may be some unknown factors that cause the correlation coefficient between the scores on the MET 6B and the total scores on the CT 2014 for the English learners majoring in engineering to be far lower than those for the English learners of a variety of majors. It is then necessary to uncover those factors, and depending on what they are, create a different version of the MET as a useful tool to measure English proficiency of engineering majors

Sugar Scrub Effects on Skin Barrier Function and Heat Retention in Low Birth Weight Infants

Objective: This investigation sought to compare changes in body heat after using a sugar scrub to bathe lowbirth weight infants (< 2,500 g), compared with those bathed using conventional baby soap, and to evaluatethe relationship between skin barrier function and changes in body heat.Design: Non-Randomized clinical trialsSetting: A neonatal intensive care unit in a university hospital in JapanParticipants: 22 Low birth weight infants for whom bathing was permittedMethods: Sebum quantity and skin temperature were each measured before and after bathing for a control groupbathed with conventional baby soap and a group bathed with a sugar scrub skin care product. Ethical approvalfor this study was obtained from Aino university of Ethics committee review board (Approval number/27)Results: The results demonstrated that both sebum quantity and skin temperature increased significantly afterbathing in the sugar scrub group compared with the baby soap group.Conclusion: Increases in sebum quantity are thought to influence the normal barrier function of skin and to helpretain skin temperature. This study suggests that the use of this skin care product can be expected to effectivelyhelp maintain body temperature in low birth weight infants, who are prone to low body temperature

Increased Systemic Glucose Tolerance with Increased Muscle Glucose Uptake in Transgenic Mice Overexpressing RXRγ in Skeletal Muscle

BACKGROUND: Retinoid X receptor (RXR) γ is a nuclear receptor-type transcription factor expressed mostly in skeletal muscle, and regulated by nutritional conditions. Previously, we established transgenic mice overexpressing RXRγ in skeletal muscle (RXRγ mice), which showed lower blood glucose than the control mice. Here we investigated their glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: RXRγ mice were subjected to glucose and insulin tolerance tests, and glucose transporter expression levels, hyperinsulinemic-euglycemic clamp and glucose uptake were analyzed. Microarray and bioinformatics analyses were done. The glucose tolerance test revealed higher glucose disposal in RXRγ mice than in control mice, but insulin tolerance test revealed no difference in the insulin-induced hypoglycemic response. In the hyperinsulinemic-euglycemic clamp study, the basal glucose disposal rate was higher in RXRγ mice than in control mice, indicating an insulin-independent increase in glucose uptake. There was no difference in the rate of glucose infusion needed to maintain euglycemia (glucose infusion rate) between the RXRγ and control mice, which is consistent with the result of the insulin tolerance test. Skeletal muscle from RXRγ mice showed increased Glut1 expression, with increased glucose uptake, in an insulin-independent manner. Moreover, we performed in vivo luciferase reporter analysis using Glut1 promoter (Glut1-Luc). Combination of RXRγ and PPARδ resulted in an increase in Glut1-Luc activity in skeletal muscle in vivo. Microarray data showed that RXRγ overexpression increased a diverse set of genes, including glucose metabolism genes, whose promoter contained putative PPAR-binding motifs. CONCLUSIONS/SIGNIFICANCE: Systemic glucose metabolism was increased in transgenic mice overexpressing RXRγ. The enhanced glucose tolerance in RXRγ mice may be mediated at least in part by increased Glut1 in skeletal muscle. These results show the importance of skeletal muscle gene regulation in systemic glucose metabolism. Increasing RXRγ expression may be a novel therapeutic strategy against type 2 diabetes

Piezo1-pannexin-1-P2X3 axis in odontoblasts and neurons mediates sensory transduction in dentinal sensitivity

According to the “hydrodynamic theory,” dentinal pain or sensitivity is caused by dentinal fluid movement following the application of various stimuli to the dentin surface. Recent convergent evidence in Vitro has shown that plasma membrane deformation, mimicking dentinal fluid movement, activates mechanosensitive transient receptor potential (TRP)/Piezo channels in odontoblasts, with the Ca2+ signal eliciting the release of ATP from pannexin-1 (PANX-1). The released ATP activates the P2X3 receptor, which generates and propagates action potentials in the intradental Aδ afferent neurons. Thus, odontoblasts act as sensory receptor cells, and odontoblast-neuron signal communication established by the TRP/Piezo channel-PANX-1-P2X3 receptor complex may describe the mechanism of the sensory transduction sequence for dentinal sensitivity. To determine whether odontoblast-neuron communication and odontoblasts acting as sensory receptors are essential for generating dentinal pain, we evaluated nociceptive scores by analyzing behaviors evoked by dentinal sensitivity in conscious Wistar rats and Cre-mediated transgenic mouse models. In the dentin-exposed group, treatment with a bonding agent on the dentin surface, as well as systemic administration of A-317491 (P2X3 receptor antagonist), mefloquine and 10PANX (non-selective and selective PANX-1 antagonists), GsMTx-4 (selective Piezo1 channel antagonist), and HC-030031 (selective TRPA1 channel antagonist), but not HC-070 (selective TRPC5 channel antagonist), significantly reduced nociceptive scores following cold water (0.1 ml) stimulation of the exposed dentin surface of the incisors compared to the scores of rats without local or systemic treatment. When we applied cold water stimulation to the exposed dentin surface of the lower first molar, nociceptive scores in the rats with systemic administration of A-317491, 10PANX, and GsMTx-4 were significantly reduced compared to those in the rats without systemic treatment. Dentin-exposed mice, with somatic odontoblast-specific depletion, also showed significant reduction in the nociceptive scores compared to those of Cre-mediated transgenic mice, which did not show any type of cell deletion, including odontoblasts. In the odontoblast-eliminated mice, P2X3 receptor-positive A-neurons were morphologically intact. These results indicate that neurotransmission between odontoblasts and neurons mediated by the Piezo1/TRPA1-pannexin-1-P2X3 receptor axis is necessary for the development of dentinal pain. In addition, odontoblasts are necessary for sensory transduction to generate dentinal sensitivity as mechanosensory receptor cells