Prevalence, predictors, and outcomes of conservative medical management in non-ST-segment elevation acute coronary syndromes in Gulf RACE-2

We assessed the prevalence, predictors, and in-hospital and long-term outcomes of conservative medical management for patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) compared with percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG). This prospective study conducted from October 2008 to June 2009 in 65 hospitals from 6 Arabian Gulf countries included 30-day and 1-year mortality follow-up for 3661 patients. Compared with conservative management group (2859 patients; 78.1%), the PCI group (638; 17.4%) had significantly better unadjusted and adjusted in-hospital (odds ratio [OR]: 0.40, 95% confidence interval [CI]: 0.17-0.97), 30-day (OR: 0.44, 95% CI: 0.24-0.76) and 1-year (OR: 0.58, 95% CI: 0.40-0.87) mortality rates. Comparison with the CABG group (164; 4.5%) yielded similar results with inclusion of patients scheduled for CABG after hospital discharge. Independent predictors of conservative medical management were mainly country of residence and history of prior CABG.     

Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matching was applied to allow unbiased comparison between treatment groups. Bleeding control was significantly higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs 68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P = 1). Thrombotic events were reported in 3.6% of treated patients with a similar incidence between rFVIIa (2.9%) and aPCC (4.8%).     

Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)

Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P < .003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclophosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first-line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level.     

Myocardial recovery in peripartum cardiomyopathy: prospective comparison with recent onset cardiomyopathy in men and nonperipartum women

BackgroundWhether myocardial recovery occurs more frequently in peripartum cardiomyopathy (PPCM) than in recent onset cardiomyopathies in men and nonperipartum women has not been prospectively evaluated. This was examined through an analysis of outcomes in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) registry.Methods and ResultsIMAC2 enrolled 373 subjects with recent onset nonischemic dilated cardiomyopathy. Left ventricular ejection fraction (LVEF) was assessed at entry and 6 months, and subjects followed for up to 4 years. Myocardial recovery was compared between men (group 1), nonperipartum women (group 2) and subjects with PPCM (group 3). The cohort included 230 subjects in group 1, 104 in group 2, and 39 in group 3. The mean LVEF at baseline in groups 1, 2, and 3 was 0.23 ± 0.08, 0.24 ± 0.08, and 0.27 ± 0.07 (P = .04), and at 6 months was 0.39 ± 0.12, 0.42 ± 0.11, and 0.45 ± 0.14 (P = .007). Subjects in group 3 had a much greater likelihood of achieving an LVEF >0.50 at 6 months than groups 1 or 2 (19 %, 34%, and 48% respectively, P = .002).ConclusionsProspective evaluation confirms myocardial recovery is greatest in women with PPCM, poorest in men, and intermediate in nonperipartum women. On contemporary therapy, nearly half of women with PPCM normalize cardiac function by 6 months.     

基于开放式三明治酶联免疫分析的雌二醇检测方法的建立

目的:通过建立开放式三明治酶联免疫分析方法（OE-ELISA）,对雌二醇进行检测。方法:通过基因拼接构建质粒后在原核表达系统中制备小分子泛素相关修饰物蛋白-大肠杆菌麦芽糖结合蛋白-抗体轻链可变区（sumo-MBP-VL）和碱性磷酸酶-抗体重链可变区（ALP-VH）融合蛋白,并从产量和可溶性角度对两种蛋白的表达条件进行优化。将得到的两种蛋白纯化后分别作为包被抗体和酶标抗体,建立检测雌二醇的OE-ELISA方法。应用竞争ELISA和OE-ELISA测定不同浓度的雌二醇标准品,绘制标准曲线并计算两种方法的敏感性。结果:在质粒中加入sumo标签后,实现了sumo-MBP-VL融合蛋白的可溶性表达。在Rosetta 宿主菌中37℃诱导后得到大量的ALP-VH和sumo-MBP-VL融合蛋白。OE-ELISA测定雌二醇标准品的标准曲线为y=0.029 6x+1.302 9,r2=0.9961,敏感性为532 pg/mL,优于竞争ELISA 803 pg/mL的敏感性。结论:成功建立了检测雌二醇的OE-ELISA方法。     

肿瘤微环境中免疫与基质细胞相关基因在肺腺癌中的预后价值

目的:鉴别与肺腺癌预后相关的免疫与基质细胞基因。方法:501例肺腺癌基因表达数据来自癌症基因组图谱（TCGA）数据库。肺腺癌样本的免疫和基质评分从ESTIMATE数据库中获取。χ2检验分析基质、免疫评分与患者临床病理特征的相关性。采用t检验以及Cytoscape中的Mcode模块筛选差异表达基因（DEGs）。采用Kaplan-Meier法绘制生存曲线。结果:基质细胞评分与M分期显著相关（χ2=6.391,P=0.011）。免疫评分与M分期（χ2=4.769,P=0.029）、T分期（χ2=11.672,P=0.009）和总生存期（χ2=6.334,P=0.009）显著相关。基于免疫评分的DEGs有262个,基于基质评分的DEGs有391个。基因功能富集分析和蛋白-蛋白相互作用网络分析差异表达基因,富集分析表明,DEGs参与调节免疫应答、抗原结合、免疫应答和受体结合。生存分析表明POSTN（P=0.0181）、PLEK（P=0.0434）、LY86（P=0.0136）、HCK（P=0.0487）对肺腺癌患者具有预后价值。结论:基质细胞相关基因POSTN高表达与患者不良预后相关,免疫细胞相关基因PLEK、LY86、HCK高表达预示患者预后较好。