高原地区健康老年人重返平原后外周血T细胞亚群变化的观察

用单克隆抗体测定了移居高原的老年人重返平原后的T细胞亚群的变化结果:①移居西宁(2260m)组、天峻(3000m)组在西宁所测的OKT_3、OKT_4、OKT_8及OKT_4/OKT_8值与在苏州所测的当地老年人无差异。②移居西宁组急返平原后OKT_3、OKT_8水平明显低于返回平原后居住一年以上者(以下简称返回组)(P<0.01～0.001)但OKT_4/OKT_8无差异。③返回组与世居苏州老年人相比,前者OKT_3、OKT_4、OKT_8及OKT_4。OKT_8增高,其中OKT_3、OKT_4增高明显(P<0.01～0.02),作者认为长期移居高原返回平原后T细胞亚群也可能存在一“脱适应”阶段,即机体重新调整重新平衡的一种形式,这一阶段可能需一年以上。     

The severity of airways obstruction as a determinant of treatment response in COPD

Guidelines recommend that patients with COPD are stratified arbitrarily by baseline severity (FEV₁) to decide when to initiate combination treatment with a long-acting β₂-agonist and an inhaled corticosteroid. Assessment of baseline FEV₁ as a continuous variable may provide a more reliable prediction of treatment effects. Patients from a 1-year, parallel-group, randomized controlled trial comparing 50 μg salmeterol (Sal), 500 μg fluticasone propionate (FP), the combination (Sal/FP) and placebo, (bid), were categorized post hoc into FEV₁ <50% and FEV₁ ≥50% predicted subgroups (n=949/513 respectively). Treatment effects on clinical outcomes – lung function, exacerbations, health status, diary card symptoms, and adverse events – were investigated. Treatment responses based on a pre-specified analysis explored treatment differences by severity as a continuous variable. Lung function improved with active treatment irrespective of FEV₁; Sal/FP had greatest effect. This improvement appeared additive in milder disease; synergistic in severe disease. Active therapy significantly reduced exacerbation rate in patients with FEV₁ <50% predicted, not in milder disease. Health status and breathlessness improved with Sal/FP irrespective of baseline FEV₁; adverse events were similar across subgroups. The spirometric response to Sal/FP varied with baseline FEV₁, and clinical benefits were not restricted to patients with severe disease. These data have implications for COPD management decisions, suggesting that arbitrary stratifications of baseline severity are not necessarily indicative of treatment efficacy and that the benefits of assessing baseline severity as a continuous variable should be assessed in future trials.     

成都市暴雨洪涝与儿童手足口病关联分析及脆弱人群亚组识别

目的 刻画成都市2011—2017年暴雨洪涝与儿童手足口病(Hand, foot and mouth disease,HFMD)之间的短期滞后关系,并进一步量化在不同性别、年龄亚组中的效应,识别脆弱人群。方法 收集整理成都市2011年1月1日—2017年12月31日的15岁以下HFMD日发病数、气象因子和暴雨洪涝发生情况数据。以暴雨洪涝为关键自变量,运用准泊松分布滞后模型,探讨了暴雨洪涝发生后0~14天的滞后效应。结果 研究发现暴雨洪涝与儿童手足口病呈正相关关系。0~7天和0~14天的累积滞后效应分别为1.11(95% CI:1.01~1.22)和1.21 (95% CI:1.04~1.41)。性别和年龄亚组分析分别表明,男童和3岁以下儿童（<1岁婴儿和1~2岁幼儿亚组）存在单日滞后统计显著的正相关关系,且0~7天和0~14天的累积滞后均显著;女童的单日滞后没有统计学意义,仅0~14天累计滞后统计显著,且效应略低于男童（女童: RR =1.23(1.00~1.51),男童: RR =1.26(1.06~1.51)）;<1岁婴儿0~7天和0~14天的累积滞后效应最强,分别为1.26(95%CI:1.02~1.57)和1.68(95%CI:1.20~2.34)。结论 暴雨洪涝会增加儿童患HFMD的风险,尤其是男童和3岁以下的婴幼儿（对1岁以下的婴儿的影响最大）。利益相关者应充分意识到暴雨洪涝的健康风险。家庭、社区、学校和政府应共同努力,减少暴雨洪涝相关的儿童HFMD。     

Influence of trial design,heterogeneity and regulatory environment on the results of clinical trials: An appraisal in the context of recent trials on acute stroke intervention

The outcome of randomized controlled trials can vary depending on the eligibility criteria of the patients entering into the trial, as well as the heterogeneity of the eligible population and/or the interventions. If the subject population and/or interventions are heterogeneous, the final outcome of the trial depends on the degree of concordance of effects of the subgroups of interventions on the subgroups of the subject population. The considerations that go into the calculation of sample size and determination of the study stopping rules also would affect the nature of the outcome of the study. In this paper we try to examine these phenomena with respect to the recent trials on endovascular therapy in acute ischemic stroke.     

Fetal growth cessation in late pregnancy: its impact on predicted size parameters used to classify small for gestational age neonates

Objective: To evaluate the impact of late 3rd trimester fetal growth cessation on anatomical birth characteristic predictions used in classifying SGA neonates.

Methods: A prospective longitudinal study was performed in 119 pregnancies with normal neonatal growth outcomes. Seven biometric parameters were measured at 3–4 weeks intervals using 3D ultrasonography. Rossavik size models were determined to predict birth characteristics at different ages. Percent Differences (% Diff) were calculated from predicted and measured birth characteristics. Growth Cessation Ages (GCA) were identified when no systematic change in % Diff values occurred after specified prediction ages. Systematic and random prediction errors were compared using different assumptions about the GCA. Predicted and measured size parameters were used to determine six new Growth Potential Realization Index (GPRI) reference ranges. Five were used to sub-classify 34 SGA neonates (weight?<?10th percentile) based on the number of abnormal GPRI values.

Results: Growth cessation ages were 38 weeks for HC, AC, mid-thigh circumference, estimated weight and mid-arm circumference. Crown-heel length GCA was 38.5 weeks. At GCA, birth characteristics had prediction errors that varied from 0.08?±?3.4% to 15.7?±?9.1% and zero % Diff slopes after 38 weeks. Assuming growth to delivery gave increased systematic and random prediction errors as well as positive % Diff slopes after 38 weeks, MA. Seventeen of the SGA neonates had 0 or 1 abnormal GPRI values [Subgroup 1] and 17 others had 2 or more abnormal values [Subgroup 2]. In Subgroup 1, 4/85 (4.7%) of GPRI's were abnormal while in Subgroup 2, 43/85 (50.6%) were abnormal. Use of only one type of GPRI for SGA subclassification resulted in substantial false negative and some false positive rates when compared to subclassification based on all five GPRI values.

Conclusions: Growth cessation occurred at approximately 38 weeks for all six birth characteristics studied. SGA neonates can be separated into normal and growth restricted subgroups based on the frequency of abnormal GPRI values (GPRI Profile Classification).     

Signaling pathway and molecular subgroups of medulloblastoma

Medulloblastoma (MB) is the most common malignant brain tumor in children. Although multimodality treatment regimens including surgery, radiotherapy and chemotherapy have greatly improved disease outcome, about one-third of MB patient remains incurable, and many long-term survivors are suffered from deleterious effects due to aggressive treatment. Understanding the signaling pathways and the genetic mechanisms contributed to MB development would be the key to develop novel therapeutic treatment strategies for improving survival and outcome of MB. In this review, we discuss the biological signaling pathways involved in MB pathogenesis. We also go through the current international consensus of four core MB subgroups namely, SHH, WNT, Group 3 and Group 4. This is adopted based on the knowledge of genomic complexity of MB as analyzed by recent high-throughput genomic technology. We talk about immunohistochemistry assays established to determine molecular subgroup affiliation. In the last part of review, we discuss how identification of molecular subgroups is going to change our routine disease diagnosis and clinical management.     

Outcomes 1 year after thrombus aspiration for myocardial infarction

Routine intracoronary thrombus aspiration before primary percutaneous coronary intervention(PCI) in patients with ST-segment elevation myocardial infarction(STEMI) has not been proved to reduce short-term mortality.We evaluated clinical outcomes at 1 year after thrombus aspiration. Methods We randomly assigned 7244 patients with STEMI to undergo manual thrombus aspiration followed by PCI or to undergo PCI alone, in a registry-based, randomized clinical trial. The primary end point of all-cause mortality at 30 days has been reported previously. Death from any cause at 1 year was a prespecified secondary end point of the trial. Results No patients were lost to follow-up. Death from any cause occurred in 5.3% of the patients(191 of 3621 patients) in the thrombus-aspiration group, as compared with 5.6%(202 of 3623) in the PCI-only group(hazard ratio, 0.94; 95% confidence interval [CI], 0.78 to 1.15; P = 0.57). Rehospitalization for myocardial infarction at 1 year occurred in 2.7% and 2.7% of the patients, respectively(hazard ratio, 0.97; 95% CI, 0.73 to1.28; P = 0.81), and stent thrombosis in 0.7% and 0.9%, respectively(hazard ratio, 0.84; 95% CI, 0.50 to1.40; P = 0.51). The composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis occurred in 8.0% and 8.5% of the patients, respectively(hazard ratio, 0.94; 95% CI, 0.80 to1.11; P = 0.48). The results were consistent across all the major subgroups, including grade of thrombus burden and coronary flow before PCI. Conclusions Routine thrombus aspiration before PCI in patients with STEMI did not reduce the rate of death from any cause or the composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis at 1 year.     

Outcomes 1 year after thrombus aspiration for myocardial infarction

Background Routine intracoronary thrombus aspiration before primary percutaneous coronary intervention(PCI) in patients with ST-segment elevation myocardial infarction(STEMI) has not been proved to reduce short-term mortality. We evaluated clinical outcomes at 1 year after thrombus aspiration.Methods We randomly assigned 7244 patients with STEMI to undergo manual thrombus aspiration followed by PCI or to undergo PCI alone, in a registry-based, randomized clinical trial. The primary end point of all-cause mortality at 30 days has been reported previously. Death from any cause at 1 year was a prespecified secondary end point of the trial.Results No patients were lost to follow-up. Death from any cause occurred in 5.3% of the patients(191 of 3621 patients) in the thrombus-aspiration group, as compared with 5.6%(202 of 3623) in the PCI-only group(hazard ratio, 0.94; 95% confidence interval [CI], 0.78 to 1.15; P = 0.57). Rehospitalization for myocardial infarction at 1 year occurred in 2.7% and 2.7% of the patients, respectively(hazard ratio, 0.97; 95% CI, 0.73 to1.28; P = 0.81), and stent thrombosis in 0.7% and 0.9%, respectively(hazard ratio, 0.84; 95% CI, 0.50 to1.40; P = 0.51). The composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis occurred in 8.0% and 8.5% of the patients, respectively(hazard ratio, 0.94; 95% CI, 0.80 to1.11; P = 0.48). The results were consistent across all the major subgroups, including grade of thrombus burden and coronary flow before PCI.Conclusion Routine thrombus aspiration before PCI in patients with STEMI did not reduce the rate of death from any cause or the composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis at 1 year.(From: N Engl J Med 2014; 371:1111-1120 September 18, 2014DOI: 10.1056 / NEJMoa1405707)