适量运动对心房颤动患者预后的影响:系统综述与Meta分析

目的 分析适量运动对于心房颤动(房颤)患者的运动能力以及远期临床预后的影响。方法 通过检索中国知网,万方,维普,Pubmed,OVID,Cochrane Central Register of Controlled Trials (CENTRAL),web of science数据库,纳入对房颤患者进行适量体育活动干预的临床试验。本研究的主要终点为静息心率,最大心率,6 min步行试验,最大运动功率,全因死亡率以及卒中发生率,用以评估适量运动对房颤患者活动耐力以及预后的影响。结果 本研究共纳入7项试验,2 452例患者,试验组为适量运动干预组,对照组为不活跃组。适量运动并不会显著增加患者的静息心率(MD=-1.68,P=0.70)以及最大心率(RD=9.72,P=0.11)。运动训练可显著提高房颤患者的运动能力,明显增加6 min步行距离(MD=59.07,95%CI=11.70-106.44,P<0.05),并且在一定程度上提高运动功率(MD=17.96,95%CI=-6.30-42.22,P=0.15)。适量运动对房颤患者的远期预后不会造成不良影响,适量运动组对比不活跃组,全因死亡率为15.7% vs 14.2%(RD=0.03,95%CI=-0.18-0.25,P=0.75);卒中发生率5.0% vs 2.9%(RD=0.02,95%CI=-0.06-0.09,P=0.69),两组差异无统计学意义。结论 适量运动可在一定程度上提高房颤患的活动耐力,且不增加卒中以及全因死亡率。     

Risk analysis for radiotherapy at the Universitätsklinikum Erlangen

PurposeRisk analysis is required by various laws and regulations in Germany and has an impact on each department of a large clinic. We provide an overview of the relevant laws and regulations in Germany and present the technical and organizational experience of introducing risk analysis in the Department of Radiation Oncology at the Universitätsklinikum Erlangen.MethodsRisk analysis was performed with an in-house developed extension of our intranet platform and ticketing system. Risks were classified according to occurrence and severity, each on a 5-level scale resulting into a risk matrix. An interdisciplinary team of six experienced members formed the core meeting weekly.ResultsA total of 38 risks and 50 measures have been identified in 41 1 h-meetings corresponding to approx. 260 working hours. Risk was distributed 8/20/13 to the categories critical (n = 8), monitoring (n = 20), and conditionally acceptable (n = 13). Risk analysis has been evaluated before and after introducing measures.ConclusionThe risk analysis method introduced has been successfully used in routine operations for over a year. Risk analysis takes time and effort. However, because experts from different disciplines meet each other every week, the overall workflow of the radiation oncology department can be improved efficiently and continuously.     

FDA对开发尼古丁替代疗法药品的要求

美国食品药品管理局（FDA）于2019年2月发布了"供企业用戒烟及相关适应症：开发尼古丁替代疗法药品的指导原则"（草案）。该指导原则介绍了FDA对尼古丁替代疗法（NRT）药品总体开发方案的建议，而我国目前尚无类似指导原则。介绍该指导原则的主要内容，期待对我国这类药的研发有益。     

Encorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations

Introduction: Combination treatment with a BRAF inhibitor and MEK inhibitor is the standard of care for patients with advanced BRAF^V600 mutation-positive melanoma. With the currently available combinations of dabrafenib plus trametinib and vemurafenib plus cobimetinib, median progression-free survival (PFS) of over 12 months has been achieved. However, treatment resistance and disease recurrence remain a clinical challenge.

Areas covered: Encorafenib in combination with bimetinib offers a new approach that may offer benefits over existing BRAF/MEK inhibitor combinations.

Expert opinion: While other BRAF/MEK inhibitor combinations have achieved a median overall survival (OS) of 22 months, patients with advanced BRAF mutation-positive melanoma treated with encorafenib plus binimetinib achieved a median OS of 33.6 months in the phase III COLUMBUS trial. PFS also appears to be improved with encorafenib plus binimetinib. This improved efficacy may be related to the distinct pharmacokinetics of encorafenib, with prolonged binding to the target molecule providing greater BRAF inhibition and increased potency compared with other drugs in the same class. Increased specificity of encorafenib may also result in better tolerability with less off-target effects, including reduced occurrence of pyrexia and photosensitivity. Encorafenib plus binimetinib seems likely to emerge as a valuable therapeutic alternative to established BRAF/MEK inhibitor combinations.     

Mesenchymal stem cell-derived exosomes attenuate phosgene-induced acute lung injury in rats

Objective: We have previously found that mesenchymal stem cell (MSC) therapy can ameliorate phosgene-induced acute lung injury (ALI). Moreover, exosomes can be used as a cell-free alternative therapy. In the present study, we aimed to assess the effect of MSC-derived exosomes on phosgene-induced ALI.

Methods: MSC-derived exosomes were isolated from MSCs through ultracentrifugation. Sprague-Dawley (SD) rats were exposed to phosgene at 8.33?g/m³ for 5?min. MSC-derived exosomes were intratracheally administered and rats were sacrificed at the time points of 6, 24 and 48?h.

Results: Compared with the phosgene group, MSC-derived exosomes reversed respiratory function alterations, showing increased levels of TV, PIF, PEF and EF50 as well as decreased levels of RI and EEP. Furthermore, MSC-derived exosomes improved pathological alterations and reduced wet-to-dry ratio and total protein content in BALF. MSC-derived exosomes reduced the levels of TNF-α, IL-1β and IL-6 and increased the IL-10 level in BALF and plasma. MSC-derived exosomes suppressed the MMP-9 level and increased the SP-C level.

Conclusions: MSC-derived exosomes exerted beneficial effects on phosgene-induced ALI via modulating inflammation, inhibiting MMP-9 synthesis and elevating SP-C level.     

Terapia de luz pulsada intensa regulada: un tratamiento complementario prometedor para la enfermedad de ojo seco

ObjectiveTo propose the Intense Pulsed Light (IPL) therapy as a helpful supplementary treatment in patients with dry eye disease.Material and methodsRetrospective cross sectional design. Medical records of patients in whom dry eye disease symptoms were not satisfactorily controlled with medical therapy alone and who underwent additional IPL with at least three sessions completed. Data were analyzed before therapy and 3 weeks after its completion to asses improvement. Determination of symptoms, through a visual analog scale; tear film stability, through tear Break Up Time (tBUT); measurement of tear secretion, through Schirmer Test; and ocular surface staining with Van Bijsterveld score were evaluated. SPSS software and nonparametric analysis of repeated measures were used. The study was approved by the ethics committee.Results50 eyes from 25 subjects were reviewed. There were 9 males (36%) and 16 females (64%), with a median age of 59 years (IQR 52-64). The median of the symptoms scale was 8 (IQR 8-9) and 3 (IQR 2-4) before and after the therapy respectively (P < .05). The median of BUT was 4 (IQR 3-5) and 10 (IQR 8-11), Schirmer test was 13 (IQR 12-15) and 15 (IQR 13-20), and Van Bijsterveld score was 3 (RIC 3-4) and 2 (IQR 2-3) before and after the therapy respectively (P < .05, for all measurements).ConclusionIPL treatment has excellent results regarding both: dry eye disease symptoms improvement and in office objective tests such as tBUT, Schirmer test and Van Bijsterveld score; IPL could be considered as an effective adjunct for dry eye disease.     

Effects of upper-body resistance exercise training on serum nesfatin-1 level,insulin resistance,and body composition in obese paraplegic men

Background

As a recently discovered adipokine, nesfatin-1 is conducive to insulin sensitivity, lipid profile, energy balance, and probably obesity.

A short bout of high-intensity exercise alters ipsilesional motor cortical excitability post-stroke

Background: Acute exercise can increase motor cortical excitability and enhance motor learning in healthy individuals, an effect known as exercise priming. Whether it has the same effects in people with stroke is unclear.

Objectives: The objective of this study was to investigate whether a short, clinically-feasible high-intensity exercise protocol can increase motor cortical excitability in non-exercised muscles of chronic stroke survivors.

Methods: Thirteen participants with chronic, unilateral stroke participated in two sessions, at least one week apart, in a crossover design. In each session, they underwent either high-intensity lower extremity exercise or quiet rest. Motor cortical excitability of the extensor carpi radialis muscles was measured bilaterally with transcranial magnetic stimulation before and immediately after either exercise or rest. Motor cortical excitability changes (post-exercise or rest measures normalized to pre-test measures) were compared between exercise vs. rest conditions.

Results: All participants were able to reach the target high-intensity exercise level. Blood lactate levels increased significantly after exercise (p < .001, d = 2.85). Resting motor evoked potentials from the lesioned hemisphere increased after exercise (mean 1.66; 95% CI: 1.19, 2.13) compared to the rest condition (mean 1.23; 95% CI: 0.64, 1.82), p = .046, d = 2.76, but this was not the case for the non-lesioned hemisphere (p = .406, d = 0.25).

Conclusions: High-intensity exercise can increase lesioned hemisphere motor cortical excitability in a non-exercised muscle post-stroke. Our short and clinically-advantageous exercise protocol shows promise as a potential priming method in stroke rehabilitation.     

Ticagrelor Versus Clopidogrel in Patients With STEMI Treated With Fibrinolysis: TREAT Trial

BackgroundThe efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.ObjectivesThe purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.MethodsThis international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.ResultsThe combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.ConclusionAmong patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088)