非致残性缺血性脑血管事件药物治疗进展

非致残性缺血性脑血管事件（non-disabling ischemic cerebrovascular events，NICE）占缺血性 脑血管病的50%～60%。近年来，NICE的治疗从最初的单药抗血小板到双联抗血小板取得了重大突破，研究证明21 d的短程、双联抗血小板方案具有更高的有效性和安全性。NICE患者进行溶栓治疗获益的同时会增加出血风险，目前对于NICE患者是否需要接受溶栓治疗仍存在争议，但可预知的是，NICE的类型、NIHSS评分、溶栓时间窗、药物剂量等可作为后续研究设计考虑的影响因素。对于携带 CYP2C19 LOF基因的NICE患者，接受替格瑞洛治疗的预后效果明显优于氯吡格雷；另外，其他基因的多态性对NICE的预后也存在较大影响，基因多态性研究或成为未来卒中治疗的一个新方向。     

Appropriate extent of surgery for aspirin-exacerbated respiratory disease

The current literature lacks strong guidelines regarding surgical management of patients with aspirin-exacerbated respiratory disease (AERD), who present with the clinical triad of chronic rhinosinusitis with nasal polyposis (CRSwNP), bronchial asthma, and aspirin/nonsteroidal anti-inflammatory drug intolerance. To further define the effectiveness of sinus surgery in treating AERD patients, this review article discusses current evidence regarding outcomes associated with more extensive surgery, the benefits of frontal sinus surgery on polyposis, and the role of Draf III intervention. Numerous studies suggest that Draf III frontal sinusotomy may be an efficacious early intervention due to increased neo-ostial patency and subsequent distribution of topical therapies. Future studies that further investigate the efficacy and safety of extensive surgery in AERD patients are warranted.     

Comparison between a new platelet count drop method PL-11, light transmission aggregometry,VerifyNow aspirin system and thromboelastography for monitoring short-term aspirin effects in healthy individuals

Platelet function has been described by many laboratory assays, and PL-11 is a new point-of-care platelet function analyzer based on platelet count drop method, which counts platelet before and after the addition of agonists in the citrated whole blood samples. The present study sought to compare PL-11 with other three major more established assays, light transmission aggregometry (LTA), VerifyNow? aspirin system and thromboelastography (TEG), for monitoring the short-term aspirin responses in healthy individuals. Ten healthy young men took 100?mg/d aspirin for 3-day treatment. Platelet function was measured via PL-11, LTA, VerifyNow and TEG, respectively. The blood samples were collected at baseline, 2 hour, 1 day during the aspirin treatment and 1 day, 5?±?1 days, 8?±?1 days after the aspirin withdrawal. Moreover, 90 additional healthy subjects were recruited to establish a reference range for PL-11. Platelet function of healthy subjects decreased significantly 2 hours after 100?mg/d aspirin intake and began to recover during 4–6 days after the aspirin withdrawal. Correlations between methods were PL-11 vs. LTA (r?=?0.614, p?<?0.01); PL-11 vs. VerifyNow (r?=?0.829, p?<?0.01); PL-11 vs. TEG (r?=?0.697, p?<?0.001). There was no significant bias between PL-11 and LTA at baseline (bias?=?1.94%, p?=?0.804) using Bland-Altman analysis, while the data of PL-11 were significantly higher than LTA (bias?=?24.02%, p?<?0.001) during the aspirin therapy. The reference range for PL-11 in healthy young individuals was from 66.8 to 90.5% (95%CI). When aspirin low-responsiveness was defined as LTA?>?20%, the cut-off values for each method were, respectively: PL-11?>?50%, VerifyNow?>?533 ARU, TEG?>?60.2%. The results of different platelet function assays were uninterchangeable for monitoring aspirin response and correlations among them were also varied. Correlations among PL-11 and other three major assays suggested the ability of PL-11 to assess the treatment effects of aspirin. But a large cohort study is needed to confirm the cut-off value of aspirin response detected by PL-11.     

子痫前期高危孕妇阿司匹林抵抗与基因多态性相关性

子痫前期是妊娠期特有的高血压疾病，近年尤其是早发型子痫前期，是孕产妇和新生儿发病和死亡的重要原因。低剂量的阿司匹林在国外已明确用于子痫前期的预防，可以减少子痫前期的发展，并降低早产和胎儿生长受限的发生率。但部分患者不能达到预期效果，存在阿司匹林抵抗。在阿司匹林预防血栓相关研究中同样存在阿司匹林抵抗现象。目前基因多态性与阿司匹林抵抗的相关性已成为研究热点。研究较多的有ABC转运蛋白家族基因、环氧合酶（COX）基因（COX-1和COX-2）、TXA2R基因、ADP受体基因、GP受体等基因多态性及其相互作用。由于其在孕妇中鲜有研究而在心脑血管疾病中研究较多，现重点从基因多态性角度阐述在心脑血管疾病中阿司匹林抵抗的可能机制，以指导阿司匹林在孕妇这类特殊人群的用药，改善妊娠结局。     

脑小血管病患者阿司匹林抵抗的发生率及其与长期预后的关系

【摘要】 目的 探讨脑小血管病（cerebral small vessel disease，CSVD）患者阿司匹林抵抗（aspirin resistance， AR）的发生率，以及AR与结局的关系。 方法 前瞻性纳入2015年8月-2017年6月诊断为CSVD的住院患者。根据血栓弹力图仪测量血小板 抑制率将患者分为AR组和非AR组。记录所有患者基线时人口学、实验室检查、影像学检查等资料，并 在2年随访期间进行影像学复查，同时记录患者新发血管事件及死亡情况。使用多因素Logistic回归分 析确定AR与结局的关系。 结果 共纳入94例患者，年龄为49～84岁，平均年龄66.20±7.37岁，男性55例（58.5%），AR的发生 率为23.4%（22/94）。AR与2年内新发腔隙性脑梗死（OR 4.70，95%CI 1.56～24.13，P =0.041）和脑白 质病变加重（OR 4.07，95%CI 1.28～11.57，P =0.038）风险相关，与新发血管事件及死亡风险无关。 结论 CSVD住院患者中AR发生率约1/5，AR与脑白质病变加重和新发腔隙性脑梗死风险相关。     

PTGS1基因多态性与急性脑梗死患者阿司匹林抗血栓疗效的相关性

目的 探讨前列腺素内过氧化物合酶1(Prostaglandin-endoperoxide synthase1, PTGS1)基因多态性与急性脑梗死患者阿司匹林抗血栓疗效的相关性。方法 回顾性分析2017年10月-2020年10月在本院接受治疗的200例急性脑梗死患者的临床资料,按照其阿司匹林抗血栓疗效将其分为阿司匹林抵抗组(n=69)和阿司匹林敏感组(n=131),分析所有患者PTGS1基因多态性情况,比较2组性别、年龄、身体质量指数(Body Mass Index,BMI)、合并症(高血压病、冠心病、糖尿病)、PTGS1基因突变、不良嗜好(吸烟、酗酒)等临床特征及生化指标[血小板计数(Blood platelet,PLT)、超敏C反应蛋白(Hypersensitive-C reactive protein,hs-CRP)]水平,利用受试者工作特征(Receiver operating characteristic,ROC)曲线分析PLT,hs-CRP预测急性脑梗死患者阿司匹林抵抗的价值,将2组有差异的指标纳入Logistic回归分析模型,进行量化赋值,明确引起急性脑梗死患者阿司匹林抵抗的危险因素。结果 本研究200例急性脑梗死患者中PTGS1基因位点以AA为主,发生率为81.50%,其突变基因位点分别为AG,GG,占人数的14.00%、4.50%。阿司匹林抵抗组年龄≥60岁、合并糖尿病、PTGS1基因突变、吸烟患者的比例及PLT,hs-CRP水平显著高于阿司匹林敏感组(P<0.05)。经ROC曲线分析PLT,hs-CRP预测急性脑梗死患者阿司匹林抵抗的曲线下面积分别为0.879、0.866。年龄≥60岁、合并糖尿病、PTGS1基因突变、吸烟、PLT≥202.255×10⁹/L,hs-CRP≥24.695 mg/L是引起急性脑梗死患者阿司匹林抵抗的危险因素。结论 PTGS1基因多态性会增加急性脑梗死患者阿司匹林抵抗风险。除此之外,高龄、糖尿病、抽烟及PLT,hs-CRP异常高表达均可能影响阿司匹林抗血栓治疗效果。