Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction

BackgroundLarge clinical trials established the benefits of sodium-glucose cotransporter 2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia.ObjectivesThe purpose of this study was to assess the effect of empagliflozin on left ventricular (LV) function and volumes, functional capacity, and quality of life (QoL) in nondiabetic HFrEF patients.MethodsIn this double-blind, placebo-controlled trial, nondiabetic HFrEF patients (n = 84) were randomized to empagliflozin 10 mg daily or placebo for 6 months. The primary endpoint was change in LV end-diastolic and -systolic volume assessed by cardiac magnetic resonance. Secondary endpoints included changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, 6-min walk test, and quality of life.ResultsEmpagliflozin was associated with a significant reduction of LV end-diastolic volume (?25.1 ± 26.0 ml vs. ?1.5 ± 25.4 ml for empagliflozin vs. placebo, respectively; p < 0.001) and LV end-systolic volume (?26.6 ± 20.5 ml vs. ?0.5 ± 21.9 ml for empagliflozin vs. placebo; p < 0.001). Empagliflozin was associated with reductions in LV mass (?17.8 ± 31.9 g vs. 4.1 ± 13.4 g, for empagliflozin vs. placebo, respectively; p < 0.001) and LV sphericity, and improvements in LV ejection fraction (6.0 ± 4.2 vs. ?0.1 ± 3.9; p < 0.001). Patients who received empagliflozin had significant improvements in peak O₂ consumption (1.1 ± 2.6 ml/min/kg vs. ?0.5 ± 1.9 ml/min/kg for empagliflozin vs. placebo, respectively; p = 0.017), oxygen uptake efficiency slope (111 ± 267 vs. ?145 ± 318; p < 0.001), as well as in 6-min walk test (81 ± 64 m vs. ?35 ± 68 m; p < 0.001) and quality of life (Kansas City Cardiomyopathy Questionnaire-12: 21 ± 18 vs. 2 ± 15; p < 0.001).ConclusionsEmpagliflozin administration to nondiabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for sodium-glucose cotransporter 2 inhibitors in the treatment of HFrEF patients independently of their glycemic status. (Are the “Cardiac Benefits” of Empagliflozin Independent of Its Hypoglycemic Activity? [ATRU-4] [EMPA-TROPISM]; NCT03485222)     

动态增强MRI鉴别乳腺良恶性肿瘤的效果及在病理分级中的作用

目的考察动态增强核磁共振成像（MRI）鉴别乳腺良恶性肿瘤的效果以及在病理分级中的应用。方法回顾性分析嘉兴市武警医院2009年1月至2012年1月收治乳腺肿瘤女性患者78例,年龄17～86岁,平均56．1±13．2岁,其中47例为手术病理诊断,31例为穿刺病理证实。并进行动态增强MRI,观察病灶形态学征象、计冷点Slope、热点Slope、冷点流出斜率和热点流出斜率。结果动态增强MRI对乳腺肿瘤良性病变和恶性病变均能100％显示。良恶性肿瘤在肿瘤形态、肿瘤边缘和均匀性方面有显著性差异（x2值分别为2．357、3．838、2．532,均P〈0．01）,恶性肿瘤主要表现为形态不规则、边缘不规则、回声不均匀。而良恶性肿瘤在肿瘤的边界和环形强化方面无显著性差异（,值分别为0．973、0．991,均P〉0．05）,热点Slope和热点流出斜率在不同级别浸润性导管癌之间无统计学差异（P〉0．05）。冷点Slope中病理Ⅱ级、Ⅲ级低于病理Ⅰ级（t=2．14,P〈0．05;t=11．0,P〈0．01）,病理分级Ⅲ低于病理分级Ⅱ（t=12．4,P〈0．01）。冷点流出斜率,病理Ⅱ级、Ⅲ级低于病理Ⅰ级（t=3．9,P〈0．05;t=6．6,P〈0．01）,病理Ⅲ级低于病理分级Ⅱ（t=3．7,P〈0．01）。结论动态增强MRI可有效辨别乳腺良性和恶性病变,并能在一定程度判断乳腺病变的病理分级。     

Biomechanics of graded running: Part II—Joint kinematics and kinetics

Compared to level running (LR), different strategies might be implemented by runners to cope with specific challenges of graded running at different speeds. The changes in joint kinetics and kinematics associated with graded running have been investigated, but their interactions with speed are unknown. Nineteen participants ran on an instrumented treadmill at five grades (0°, ±5° and ± 10°) and three speeds (2.50, 3.33 and 4.17 m/s), while 3D motion and forces were recorded. Three speed × five-grade repeated-measures ANOVA was used to analyze kinetic and kinematic variables. A speed × grade interaction was observed for hip range of motion (ROM). Downhill running (DR) at fastest speed did not reduce ROM at the hip, compared to LR. Compared to LR, it was observed that the hip joint was responsible for a greater contribution of energy generation while running at the fastest speed at +10°. Speed × grade interactions were also observed for the energy absorption, peak moment, and peak power at the knee. Contrary to LR, running faster during UR did not require higher peak power at the knee. Finally, DR at the fastest speed did not increase peak negative power at the knee compared to LR. This study demonstrates that ankle, knee, and hip joint kinetics depend on speed and grade of running, while the effect of grade on joint kinematics was not substantially modulated by speed.     

肥厚型心肌病磁共振钆剂延迟增强与心电图 QTe/RR的关系

摘要：目的 探讨肥厚型心肌病（HCM）磁共振钆剂延迟增强与动态心电图QTe/RR斜率的关系。方法 将本院 2016 年 1 月—2017 年 6 月接诊的 96 例 HCM 患者,根据心脏磁共振扫描（CMR）是否出现钆剂延迟增强（LGE）分为 LGE阳性组和LGE阴性组。采用评分法评估LGE阳性组患者LGE透壁程度。所有受试者行24 h动态心电图检查, 计算心率（HR）、QT间期及QTe/RR斜率。分析LGE阳性组总LGE评分与QTe/RR斜率之间的相关性,分析LGE透壁 程度和QTe/RR斜率与患者预后的关系。结果 CMR结果显示LGE阳性51例（53.13%）,LGE阴性45例（46.87%）; LGE阳性组与LGE阴性组左心室射血分数（LVEF：0.412±0.092 vs. 0.508±0.083）、左心室舒张末期容积［LVEDV（mL）： 173.91±43.68 vs.148.52±31.77］及左心室舒张末期后壁厚度［LVPWD（mm）：13.26±2.81 vs. 12.15±2.37］比较差异有统 计学意义（t分别为5.301、3.219、2.077,均P＜0.05）;LGE阳性组QT间期（ms：439.67±25.82 vs. 411.53±31.66）、QTe/RR 斜率（0.20±0.05 vs. 0.16±0.03）均高于 LGE 阴性组（t 分别为 4.794、4.674,均 P＜0.05）;LGE 阳性组总 LGE 评分为 （26.37±7.52）分,与QTe/RR斜率呈正相关（r=0.742,P＜0.001）;LGE阳性组室性心律失常、心源性猝死等不良反应发 生率高于LGE阴性组（17.65% vs. 4.44%,c2=4.107,P＜0.05）;总LGE评分、QTe/RR斜率与患者室性心律失常、心源性 猝死有关（P＜0.05）。结论 HCM患者LGE程度与QTe/RR斜率显著相关,综合评估两项指标可能更有助于HCM预 后判断     

先天性脊柱侧凸合并冠状面骶骨倾斜的手术治疗

目的探讨先天性脊柱侧凸合并冠状面骶骨倾斜的临床特征及手术疗效。方法回顾性分析2007年1月—2013年12月山西医科大学第二医院骨科365例先天性脊柱侧凸患者中存在冠状面骶骨倾斜的11例患者的临床资料,其中男6例,女5例;年龄4—34岁,平均13．5岁;均为腰椎畸形病例。分析比较其手术前后冠状面骶骨倾斜角（CSS）、Cobb角、锁骨角（CA）、顶椎至骶中线（CSVL）的垂直距离（Apex—CSVL）、腰椎前凸角（LL）、骶骨倾斜角（SS）、骨盆投射角（PI）、骨盆倾角（PT）等参数的改变,并采用Wilcoxon符号秩和检验进行统计学分析。结果CSS、CA、LL、PI及PT等参数手术前后比较差异均无统计学意义（丁值分别为12．5、16．0、18．5、18．0、19．5,P值均〉0．05）;而手术后平均Cobb角由术前的48．5°改善为17．4°,平均Apex—CSVL由术前的3．2cm改善为1．8cm,平均SS由28．1°改善为33．8°,差异均有统计学意义（r值分别为0．0、0．0、5．0,P值均〈0．05）。结论先天性脊柱侧凸合并冠状面骶骨倾斜多发生于腰椎畸形的病例中,LL和SS较正常减小,手术治疗能够改善其冠状面和矢状面平衡。     

Calculation of Clinical r.b.e. Values for Neutrons

Summary

A method is described for calculating r.b.e. values for normal tissues at risk in clinical neutron beam therapy. This is based on the assumption that with high l.e.t. radiations the slope of the cell survival curve is steeper, mainly in the initial or low-dose region. This effect is quantified by using two coefficients, one (ε) to produce a proportionate increase in the initial slope, and a second (η) determining the change in the terminal slope (D₀) of the survival curve.

Analysis of published experimental data shows ε to be a variable quantity, different for different tissues; ε is larger when the survival curve has a large shoulder or slope ratio (ρ). By contrast, η is relatively constant (for a given beam) and less dependent on the tissue or end-point studied.

For low doses, the r.b.e. approaches ε, which can be calculated given η (characteristic of the beam) and ρ (characteristic of the relevant tissue) [ε = η + ρ(η ? 1)]. This provides a useful approximation to the clinical r.b.e. for specific tissues relative to conventionally fractionated low-l.e.t. photons.     

窦性心率震荡与冠心病冠脉病变累及程度的相关性分析

目的 观察窦性心率震荡各指标与冠心病患者病变累及程度之间的关系.方法 选择行冠脉造影和24h动态心电图检查的患者93例,根据冠脉造影的结果分为阳性组（69例）、阴性组（24例）,根据冠状动脉病变累及程度分为单支血管病变组（23例）、双支血管病变组（21例）和三支血管病变组（15例）,均于入院时行24h动态心电图检查,并计算震荡初始值和震荡斜率,进行统计分析.结果 阳性组HRT值[TO：（0.0463±0.0310）、TS：（3.9257±3.8741）ms/RR],阴性组值[TO：（-0.0393±8.9786）（12.9972±8.9786）ms/RR],（P ＜0.01）;单支病,TS：两组间差异有统计学意义变组HRT值[TO：（0.0069±0.0058）、TS：（6.6098±3.9966）ms/RR]、双支病变组HRT值[TO：（0.0369±0.0213）、TS：（3.6867±2.4173）ms/RR]、三支病变组HRT值[TO：（0.0985±0.0769）、TS：（0.7897±0.7327）ms/RR],HRT值除TO在单支病变组与双支病变组间差异无统计学意义（P ＞0.05）外,各组间均有统计学意义（P ＜0.01）.结论 窦性心率震荡是一种评价自主神经功能的简便的无创检测方法;窦性心率震荡与冠心病患者病变累及程度有一定的相关性,冠脉病变累及程度越重,窦性心率震荡现象越不明显.     

Variability of the computerized single-breath nitrogen washout test in healthy adults. Results from a field survey in a French rural area

Summary. Within-subject (difference between paired tests, or coefficient of variation [c. var.] of three consecutive measurements) and between-subjects (standard deviation of the mean group) variability were assessed for the variables derived from the single-breath nitrogen (SBN₂) test in a group of healthy, asymptomatic subjects (n= 289) aged 20–64 years, from a rural area in North-East France. Duplicate measurements in 99 subjects showed excellent agreement between the two attempts (correlation coefficients between 0.94 and 0.98) for static lung volumes and the alveolar N₂ slope (PIII); closing volumes (CV) were more variable (r= 0.77 for absolute value, 0.79 for % VC) while closing capacities (CC) were in intermediate position (r= 0.86 for absolute value, and 0.88 for % TLC). The variability of three consecutive measures in 190 subjects showed the coefficients of variation to be low for static volumes and closing capacity (2.4–7.4%) and higher for PIII (15.1%) and CV or CV7VC (18.2 and 17.8%). The analysis of variance did not detect significant differences between the three sets of measurements, with the exception of a progressive increase of vital capacity (VC), and decrease in residual volume (RV) from test 1 to test 3, the total lung capacity being the same. Variability was uninfluenced by age or sex, except a higher c. var. for female VC as compared to males (2.8 vs. 2.2%, P= 0.02) and a higher variability of TLC (2.9 vs. 2.3%, P= 0.03) and VC (2.8 vs. 1.9%, P= 0.003) in people older than 40 years as opposed to those younger than 40 years.