ダパグリフロジン投与における肥満２型糖尿病患者の治療満足度への影響：a patient reported outcome study (PRO study).

Background: The benefits of sodium glucose cotransporters 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus include plasma glucose control, reduction in body weight and blood pressure, and low risk of hypoglycemia, although they may also cause genitourinary infections, polyuria, or volume depletion. It is not clear whether dapagliflozin, an SGLT2 inhibitor, improves treatment satisfaction among patients in a comprehensive way despite the negative side effects. This study assessed the effect of dapagliflozin on glycosylated hemoglobin (HbA1c), body weight, and treatment satisfaction in overweight patients with type 2 diabetes mellitus treated with oral hypoglycemic agents. Methods: This multicenter, open-label, single-arm observational study included patients with type 2 diabetes mellitus administering dapagliflozin 5 or 10 mg per day for 14 weeks. Changes in treatment satisfaction were evaluated using a new version of the Oral Hypoglycemic Agent-Questionnaire (OHA-Q ver. 2) consisting of 23 items. Correlation between treatment satisfaction and HbA1c levels and body weight were analyzed using the Spearman's rank-correlation coefficient. Results: Of the 221 patients enrolled, 188 completed the study. Mean HbA1c decreased from 7.8 ± 0.7% (62.1 ± 7.5 mmol/mol) to 7.3 ± 0.8% (55.9 ± 8.7 mmol/mol) (change - 0.6 ± 0.7%, P < 0.001) and body weight decreased from 82.5 ± 14.6 to 80.7 ± 14.8 kg (change - 2.3 ± 2.8 kg, P < 0.001). OHA-Q ver. 2 was validated as well, the mean OHA-Q ver. 2 total score increased from 44.3 ± 9.4 to 46.6 ± 9.8 (best score 69, worst score 0; change 2.3 ± 6.6, P < 0.001). The change in body weight significantly correlated with the OHA-Q ver. 2 total score (Spearman's ρ = - 0.17, P = 0.035). The change in HbA1c levels significantly correlated with the satisfaction subscale score (Spearman's ρ = - 0.19, P = 0.011). Conclusions: Dapagliflozin significantly improved treatment satisfaction among patients with type 2 diabetes mellitus for 14 weeks. Body weight loss significantly correlated with treatment satisfaction.Trial registration UMIN-CTR: UMIN000016304.博士（医学）・甲第694号・平成31年3月15日© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice

Resistin-like molecule β (RELMβ) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELMβ to non-alcoholic steatohepatitis (NASH) development. First, RELMβ knock-out (KO) mice were shown to be resistant to methionine-choline deficient (MCD) diet-induced NASH development. Since it was newly revealed that Kupffer cells in the liver express RELMβ and that RELMβ expression levels in the colon and the numbers of RELMβ-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELMβ-KO mice to distinguish between the contributions of RELMβ in these two organs. These experiments revealed the requirement of RELMβ in both organs for full manifestation of NASH, while deletion of each one alone attenuated the development of NASH with reduced serum lipopolysaccharide (LPS) levels. The higher proportion of lactic acid bacteria in the gut microbiota of RELMβ-KO than in that of wild-type mice may be one of the mechanisms underlying the lower serum LPS level the former. These data suggest the contribution of increases in RELMβ in the gut and Kupffer cells to NASH development, raising the possibility of RELMβ being a novel therapeutic target for NASH

Symptomatic periesophageal vagal nerve injury by different energy sources during atrial fibrillation ablation

BackgroundSymptomatic gastric hypomotility (SGH) is a rare but major complication of atrial fibrillation (AF) ablation, but data on this are scarce.ObjectiveWe compared the clinical course of SGH occurring with different energy sources.MethodsThis multicenter study retrospectively collected the characteristics and clinical outcomes of patients with SGH after AF ablation.ResultsThe data of 93 patients (67.0 ± 11.2 years, 68 men, 52 paroxysmal AF) with SGH after AF ablation were collected from 23 cardiovascular centers. Left atrial (LA) ablation sets included pulmonary vein isolation (PVI) alone, a PVI plus a roof-line, and an LA posterior wall isolation in 42 (45.2%), 11 (11.8%), and 40 (43.0%) patients, respectively. LA ablation was performed by radiofrequency ablation, cryoballoon ablation, or both in 38 (40.8%), 38 (40.8%), and 17 (18.3%) patients, respectively. SGH diagnoses were confirmed at 2 (1–4) days post-procedure, and 28 (30.1%) patients required re-hospitalizations. Fasting was required in 81 (92.0%) patients for 4 (2.5–5) days; the total hospitalization duration was 11 [7–19.8] days. After conservative treatment, symptoms disappeared in 22.3% of patients at 1 month, 48.9% at 2 months, 57.6% at 3 months, 84.6% at 6 months, and 89.7% at 12 months, however, one patient required surgery after radiofrequency ablation. Symptoms persisted for &gt;1-year post-procedure in 7 patients. The outcomes were similar regardless of the energy source and LA lesion set.ConclusionsThe clinical course of SGH was similar regardless of the energy source. The diagnosis was often delayed, and most recovered within 6 months, yet could persist for over 1 year in 10%

Clinical impact of the loss of chromosome 7q on outcomes of patients with myelodysplastic syndromes treated with allogeneic hematopoietic stem cell transplantation

We conducted a nationwide retrospective study to evaluate the prognostic influence of +1, der(1;7)(q10;p10) [hereafter der(1;7)] and ?7/del(7q) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for de novo myelodysplastic syndromes (MDS). In this database, 69 MDS patients with der(1;7), 75 with ?7/del(7q), and 511 with normal karyotype (NK) underwent allo-HSCT at advanced disease status. The 3-year overall survival (OS) and cumulative incidence of relapse (CIR) were 50.4 and 19.4% for those with der(1;7), 36.2 and 38.4% for ?7/del(7q),and 51.1 and 20.7% for NK, respectively. In the multivariate analysis, the presence of ?7/del(7q) correlated with a significantly shorter OS (HR [95% CI], 1.38 [1.00?1.89]; P = 0.048) and higher CIR (HR, 2.11 [1.36?3.28]; P = 0.001) than those with NK. There were 23 patients with der(1;7), 29 with ?7/del(7q), and 347 with NK who underwent allo-HSCT at early disease status.The 3-year OS and CIR were as follows: 47.3 and 9.5% for the der(1;7) group, 70.5 and 13.8% for ?7/del(7q), and 70.9 and 5.6% for NK,respectively. No significant differences were observed in OS and CIR among three groups. The impact of the loss of chromosome 7q on OS and CIR may differ based on its type and disease status after allo-HSCT for MDS

Increase of Na-K-ATPase activity, glutamate, and aspartate uptake in dog erythrocytes associated with hereditary high accumulation of GSH, glutamate, glutamine, and aspartate.

We have found convincing evidence for the presence of Na-K-ATPase and high potassium (K) and low sodium (Na) concentrations in the erythrocytes of some dogs associated with hereditary high concentrations of erythrocyte glutathione and some amino acids, glutamate, glutamine, and aspartate. The Na-K-ATPase activity of the erythrocyte membranes of the dogs was about 3 times that of human erythrocyte membranes, whereas the enzyme activity was not detected in control dogs with a normal level of blood glutathione. The Michaelis constant of the enzyme for ATP (Km ATP) was 6.6 X 10(-3)M in the dogs' erythrocytes and 5.0 X 10(-4)M in the human erythrocytes. The concentration of K in the erythrocytes in the dogs examined was about 11 times that of the controls, whereas the erythrocyte Na concentration in the dogs was about one-third that of the controls. The concentrations of K and Na in the plasma of the dogs were equal to those of the controls. Furthermore, L-3H-glutamate and L-3H-aspartate uptake by those cells with high activity of Na-K-ATPase greatly increased, while L-3H-glutamine uptake was unchanged. It appeared that Na+ and K+ gradients created by Na-K-ATPase across the cell membrane might stimulate glutamate and aspartate uptake by the cells, thus causing the high accumulation of such amino acids in the cells

Heat Transfer Enhancement of Water Flow in a Straight Pipe with Drag Reduction Surfactant by Using Wire Coil

This paper has dealt with the heat transfer enhancement of flowing water with flow drag reduction additive into a heat transfer tube by inserting wire coils. The non-ion type surfactant was used as the additive to decrease the pipe flow resistance for the heat energy transport system. However, the decrease in the flow resistance was allowed to reduce the heat transfer coefficient in the heat transfer tube. Some kinds of wire coils having different diameters were tried to enhance the heat transfer in the heat transfer tube. The effects of wire coils on the pipe friction and the heat transfer coefficients were elucidated under various experimental parameters of flow velocity, wire coil diameter, pitch and length.熱媒体水に鎖状高分子や界面活性剤等を微量添加することによる流動抵抗低減効果（トムズ効果）を利用した熱エネルギー輸送技術が注目されており、実用化に向けて様々な研究が行われている。著者らは、流動抵抗低減剤としての界面活性剤（第4級アンモニウム塩）を添加した水を、直円管内に流動させた場合の流動抵抗や熱伝達の測定、そして数値シミュレーションによる管内流動抵抗の予測検討結果を報告してきた。さらに、著者らは、実際の配管系を想定して、界面活性剤添加水による曲管内の流動抵抗と熱伝達特性の解明を行ってきた。一方において、使用済み界面活性剤の廃棄処理の問題、そして流動抵抗低減剤使用に伴う管内熱伝達の減少による熱交換効率の低下等、この種の流動抵抗低減法の欠点も指摘されている。後者の欠点を克服するために、熱交換器入口部にミセルスクィーザーを設けて界面活性剤の棒状ミセルを一時的に分断し、流動抵抗低減効果を消失させる方法や熱交換器の伝熱面にラムダ翼列状の乱流促進体の設置や伝熱面を祖面にすることによって、伝熱促進を検討した研究も行われ始めている。本研究は、」流動抵抗低減用界面活性剤利用による円管式熱交換器内の熱伝達低下を解消させるために、乱流促進体としてワイヤーコイルを円管内に挿入した場合の熱伝達促進効果と流動抵抗の関係を実験的に明らかにしようとするものである。このワイヤーコイルによる乱流促進法は、大幅に設備の改修を行うことなく既設の熱交換器への適応が可能であるなど、従来の方法よりも早急な実用化が期待される。本実験に用いる流動抵抗低減用の界面活性剤としては、環境負荷の小さい非イオン性界面活性剤を採用し、ワイヤーコイル形状（素線径、ピッチおよび長さ）や界面活性剤添加水の流速が直円管内の熱伝達促進に及ぼす影響の検討を行うものである