Tissue Plasminogen Activator

组织型纤溶酶原激活剂
  • 文章类型: Case Reports
    静脉溶栓是急性缺血性卒中的标准治疗方法。我们在此报告摩洛哥私营部门的溶栓警报病例我们对2022年1月至2023年9月AlBadie国际私人诊所急诊科收治的所有突发性神经功能缺损患者进行了前瞻性研究。流行病学,收集了临床和病因学特征以及门诊和住院延误的数据.该研究包括60名患者。平均入院延迟为198.36±79.23分钟。NIHSS(美国国立卫生研究院卒中量表)平均得分为10.41±4.97。平均成像时间为26.68±9.63分钟。缺血性卒中是最常见的诊断(85%),其次是“中风模仿”(11.6%)。13例患者接受替奈普酶溶栓治疗。从入院到开始溶栓的平均时间为107.15±24.48分钟。溶栓后24小时的随访影像学显示3例患者有症状性出血转化。六名患者被转移到哈桑二世大学医院进行溶栓和/或机械血栓切除术。三个月后,4例患者自主(Rankin评分在0和2之间变化)。我们的经验表明,必须减少门诊和住院患者的治疗延误,以增加接受溶栓治疗的患者比例。
    Intravenous thrombolysis is the standard treatment for acute ischemic stroke. We here report the cases of thrombolysis alert in the private sector in Morocco We conducted a prospective study of all patients with neurological deficit of sudden onset occurred within the first 12 hours admitted to the Emergency Department of the Al Badie international private clinic from January 2022 to September 2023. Epidemiological, clinical and etiological characteristics as well as data on outpatient and inpatient delays were collected. Sixty patients were included in the study. The average admission delay was 198.36 ± 79.23 minutes. The mean NIHSS (National Institutes of Health Stroke Scale) score was 10.41 ± 4.97. The average time for imaging was 26.68 ± 9.63 minutes. Ischaemic stroke was the most common diagnosis (85%), followed by \"stroke mimics\" (11.6%). Thirteen patients underwent thrombolysis with tenecteplase. The mean time from admission to the initiation of thrombolysis was 107.15 ± 24.48 minutes. Follow-up imaging at 24 hours post thrombolysis revealed symptomatic haemorrhagic transformation in 3 patients. Six patients were transferred to the Hassan II University Hospital for thrombolysis and/or mechanical thrombectomy. After 3 months, 4 patients were autonomous (Rankin score changed between 0 and 2). Our experience shows that it is imperative to reduce outpatient and inpatient delays in treatment in order to increase the proportion of patients treated with thrombolysis.
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  • 文章类型: Journal Article
    背景:收缩压(SBP)是卒中早期神经功能恶化(END)的预测因子。我们对ARAMIS试验进行了二次分析,以研究基线SBP是否影响双联抗血小板与静脉注射阿替普酶对END的影响。
    方法:该事后分析包括治疗后分析集中的患者。根据SBP在入院时,患者分为SBP≥140mmHg和SBP<140mmHg亚组.在每个子组中,根据实际接受的研究药物,将患者进一步分为双重抗血小板治疗组和静脉注射阿替普酶治疗组.主要结果是结束,定义为在24小时内NIHSS评分从基线增加≥2。我们研究了双联抗血小板和静脉注射阿替普酶对SBP亚组END的影响及其与亚组的相互作用效应。
    结果:共纳入723例接受治疗的分析组患者:344例被分配到双重抗血小板组,379例被分配到静脉阿替普酶组。对于主要结果,在SBP≥140mmHg的亚组中,双联抗血小板的治疗效果更高(调整RD,-5.2%;95%CI,-8.2%至-2.3%;p<0.001),SBP<140mmHg亚组无影响(调整RD,-0.1%;95%CI,-8.0%至7.7%;p=0.97),但未发现亚组之间的显著交互作用(调整后p=0.20).
    结论:在轻度非致残性急性缺血性卒中患者中,当基线SBP≥140mmHg时,双重抗血小板在预防24小时内END方面可能优于阿替普酶.
    BACKGROUND: Systolic blood pressure (SBP) was a predictor of early neurological deterioration (END) in stroke. We performed a secondary analysis of ARAMIS trial to investigate whether baseline SBP affects the effect of dual antiplatelet versus intravenous alteplase on END.
    METHODS: This post hoc analysis included patients in the as-treated analysis set. According to SBP at admission, patients were divided into SBP ≥140 mmHg and SBP <140 mmHg subgroups. In each subgroup, patients were further classified into dual antiplatelet and intravenous alteplase treatment groups based on study drug actually received. Primary outcome was END, defined as an increase of ≥2 in the NIHSS score from baseline within 24 h. We investigated effect of dual antiplatelet vs intravenous alteplase on END in SBP subgroups and their interaction effect with subgroups.
    RESULTS: A total of 723 patients from as-treated analysis set were included: 344 were assigned into dual antiplatelet group and 379 into intravenous alteplase group. For primary outcome, there was more treatment effect of dual antiplatelet in SBP ≥140 mmHg subgroup (adjusted RD, -5.2%; 95% CI, -8.2% to -2.3%; p < 0.001) and no effect in SBP <140 mmHg subgroup (adjusted RD, -0.1%; 95% CI, -8.0% to 7.7%; p = 0.97), but no significant interaction between subgroups was found (adjusted p = 0.20).
    CONCLUSIONS: Among patients with minor nondisabling acute ischemic stroke, dual antiplatelet may be better than alteplase with respect to preventing END within 24 h when baseline SBP ≥140 mmHg.
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  • 文章类型: Journal Article
    纤维蛋白溶解的生物标志物在急性免疫反应(过敏反应和血管性水肿)期间升高,尽管目前尚不清楚纤维蛋白溶解是否与疾病严重程度相关。
    我们研究了通过血栓弹力图测量的最大溶解(ML)与急性免疫反应严重程度之间的可能关联。
    我们在一家高容量急诊科招募了急性免疫反应患者。使用5级量表评估急诊住院时和结束时的临床疾病严重程度,从局部症状到心脏骤停。我们通过血栓弹力图确定了入院时的ML(ROTEM的外在[EXTEM],和抑肽酶[APTEM]测试),表示为ML%。纤溶亢进定义为EXTEM中ML>15%,通过添加抑肽酶(APTEM)可以逆转。我们使用精确的逻辑回归来研究ML%与疾病严重程度(1级和2级[轻度]vs3-5级[严重])之间以及纤溶亢进与疾病严重程度之间的关系。
    我们包括31名患者(71%为女性;中位年龄,52[IQR,35-58]年;10[32%]有严重反应)。有严重症状的患者的ML%更高(21[IQR,12-100]vs10[IQR,4-17]).Logistic回归发现ML%和症状严重程度之间存在显著关联(比值比,1.07;95%CI,1.01-1.21;P=.003)。在6例患者中检测到纤溶亢进,并发现与严重症状有关(比值比,17.59;95%CI,1.52-991.09;P=0.02)。D-二聚体,胰蛋白酶,免疫球蛋白E浓度随免疫反应的严重程度而增加。
    ML,通过血栓弹力图量化,与急性免疫反应的严重程度有关。
    UNASSIGNED: Biomarkers of fibrinolysis are elevated during acute immunologic reactions (allergic reactions and angioedema), although it is unclear whether fibrinolysis is associated with disease severity.
    UNASSIGNED: We investigated a possible association between maximum lysis (ML) measured by thromboelastography and the severity of acute immunologic reactions.
    UNASSIGNED: We recruited patients with acute immunologic reactions at a high-volume emergency department. Clinical disease severity at presentation and at the end of the emergency department stay was assessed using a 5-grade scale, ranging from local symptoms to cardiac arrest. We determined ML on admission by thromboelastography (ROTEM\'s extrinsic [EXTEM], and aprotinin [APTEM] tests), expressed as ML%. Hyperfibrinolysis was defined as an ML of >15% in EXTEM, which was reversed by adding aprotinin (APTEM). We used exact logistic regression to investigate an association between ML% and disease severity (grades 1 and 2 [mild] vs 3-5 [severe]) and between hyperfibrinolysis and disease severity.
    UNASSIGNED: We included 31 patients (71% female; median age, 52 [IQR, 35-58] years; 10 [32%] with a severe reaction). ML% was higher in patients with severe symptoms (21 [IQR, 12-100] vs 10 [IQR, 4-17]). Logistic regression found a significant association between ML% and symptom severity (odds ratio, 1.07; 95% CI, 1.01-1.21; P = .003). Hyperfibrinolysis was detected in 6 patients and found to be associated with severe symptoms (odds ratio, 17.59; 95% CI, 1.52-991.09; P = .02). D-dimer, tryptase, and immunoglobulin E concentrations increased with the severity of immunologic reactions.
    UNASSIGNED: ML, quantified by thromboelastography, is associated with the severity of acute immunologic reactions.
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  • 文章类型: Journal Article
    脑出血风险与血脂的关系是否因性别而异尚不清楚。本研究旨在探讨使用重组组织型纤溶酶原激活剂(r-tPA)接受静脉溶栓治疗的急性缺血性卒中(AIS)患者的血脂状况与症状性脑出血(sICH)风险之间的潜在性别差异。
    这项多中心回顾性观察性研究分析了静脉r-tPA治疗的AIS患者。sICH定义为任何出血亚型在静脉溶栓后36小时内美国国立卫生研究院卒中量表(NIHSS)评分恶化4分或更高.我们使用逻辑回归模型对潜在的混杂因素进行了校正,评估了每种性别的sICH血脂谱的比值比(OR)和95%置信区间(CI)。
    957名参与者(平均年龄68岁(四分位距,59-75),男性628人(65.6%),观察到56例sICH事件(男性36例(5.7%),女性20例(6.1%))。在校正混杂因素后,随着血清甘油三酯水平的升高,男性sICH的风险降低(与最低三元组相比,中等三分位数或0.39,95%CI[0.17-0.91],最高三分位数或0.33,95%CI[0.13-0.84],总体p=0.021;每增加一个点,调整后OR0.29,95%CI[0.13-0.63],p=0.002)。男性血清总胆固醇和低密度脂蛋白(LDL)水平均与sICH无关。在女性中,任何血脂水平与sICH风险之间均无关联.
    这项研究表明,血清甘油三酯水平与sICH之间的关联可能因性别而异。在男人中,甘油三酯水平升高降低sICH的风险;在女性中,这个协会已经失去了。需要进一步研究与甘油三酯相关的卒中风险性别差异的生物学机制。
    UNASSIGNED: Whether the relationship of intracerebral bleeding risk with lipid profile may vary by sex remains unclear. This study aims to investigate potential sex differences in the association between lipid profile and the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis using recombinant tissue plasminogen activator (r-tPA).
    UNASSIGNED: This multicenter retrospective observational study analyzed patients with AIS treated with intravenous r-tPA. sICH was defined as a worsening of 4 or higher points in the National Institutes of Health Stroke Scale (NIHSS) score within 36 hours after intravenous thrombolysis in any hemorrhage subtype. We assessed the odds ratio (OR) with 95% confidence interval (CI) of lipid profile for sICH for each sex using logistic regression models adjusted for potential confounding factors.
    UNASSIGNED: Of 957 participants (median age 68 (interquartile range, 59-75), men 628 (65.6%)), 56 sICH events (36 (5.7%) in men and 20 (6.1%) in women) were observed. The risk of sICH in men decreased with increasing serum levels of triglyceride after adjustment for confounding factors (vs lowest tertile, medium tertile OR 0.39, 95% CI [0.17-0.91], top tertile OR 0.33, 95% CI [0.13-0.84], overall p = 0.021; per point increase, adjusted OR 0.29, 95% CI [0.13-0.63], p = 0.002). Neither serum levels of total cholesterol nor low-density lipoprotein (LDL) was associated with sICH in men. In women, there was no association between any of the lipid levels and the risk of sICH.
    UNASSIGNED: This study indicated that the association between serum levels of triglyceride and sICH may vary by sex. In men, increased triglyceride levels decrease the risk of sICH; in women, this association was lost. Further studies on the biological mechanisms for sex differences in stroke risk associated with triglyceride are needed.
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  • 文章类型: Journal Article
    背景:静脉替奈普酶增加了灌注成像可挽救的脑组织患者的再灌注,作为缺血性卒中的溶栓药物,可能优于阿替普酶。我们旨在评估替奈普酶与阿替普酶对通过灌注成像选择的患者的临床结局的非劣效性。
    方法:这个国际,多中心,开放标签,平行组,随机化,临床非劣效性试验纳入了来自8个国家35家医院的患者.参与者年龄在18岁或以上,在缺血性卒中发作或最后一次已知的4·5小时内,没有考虑血管内血栓切除术,并满足脑灌注成像的目标不匹配标准。通过使用集中式网络服务器将患者随机分配(1:1),并随机排列块,以静脉注射替奈普酶(0·25mg/kg)或阿替普酶(0·90mg/kg)。主要结果是3个月时无残疾患者的比例(改良Rankin量表0-1),在意向治疗人群和符合方案人群中通过掩盖审查进行评估。我们的目标是招募832名参与者,以产生90%的能力(单侧α=0·025),以检测0·08的风险差异,绝对非劣效性为-0·03。该试验已在澳大利亚新西兰临床试验注册中心注册,ACTRN12613000243718和欧盟临床试验注册,EudraCT编号2015-002657-36,已完成。
    结果:在宣布其他试验结果显示替奈普酶与阿替普酶的非劣效性后,招募提前停止。在2014年3月21日至2023年10月20日之间,共纳入680例患者,并随机分配给替奈普酶(n=339)和阿替普酶(n=341)。所有患者均被纳入意向治疗分析(5例患者的主要结局数据缺失采用多重插补).74名参与者违反了议定书,因此,符合方案的人群包括601人(替奈普酶组295人,阿替普酶组306人).参与者的平均年龄为74岁(IQR63-82),基线美国国立卫生研究院卒中量表得分为7分(4-11分),260人(38%)为女性。在意向治疗分析中,主要结局发生在分配给替奈普酶的335名参与者中的191名(57%)和分配给阿替普酶的340名参与者中的188名(55%)(标准化风险差异[SRD]=0·03[95%CI-0·033至0·10],单尾伪劣=0·031)。在符合方案的分析中,主要结局发生在分配给替奈普酶的295名参与者中的173名(59%)和分配给阿替普酶的306名参与者中的171名(56%)(SRD0·05[-0·02至0·12],单尾伪劣=0·01)。替奈普酶组的337例患者中有9例(3%)和阿替普酶组的340例患者中有6例(2%)有症状性颅内出血(未调整的风险差异=0·01[95%CI-0·01至0·03])在开始治疗90天内死亡(SRD0·02[95%CI-0·05]0。
    结论:我们的研究结果为加强替奈普酶对阿替普酶的非劣效性提供了进一步的证据,特别是当灌注成像用于识别符合再灌注条件的卒中患者时。尽管在符合方案的人群中实现了非劣效性,在意向治疗分析中没有达到,可能是由于样本量的限制。尽管如此,在早期时间窗内大规模实施灌注CT以协助患者选择静脉溶栓被证明是可行的.
    背景:澳大利亚国家健康医学研究委员会;勃林格键英格尔海姆。
    BACKGROUND: Intravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging.
    METHODS: This international, multicentre, open-label, parallel-group, randomised, clinical non-inferiority trial enrolled patients from 35 hospitals in eight countries. Participants were aged 18 years or older, within 4·5 h of ischaemic stroke onset or last known well, were not being considered for endovascular thrombectomy, and met target mismatch criteria on brain perfusion imaging. Patients were randomly assigned (1:1) by use of a centralised web server with randomly permuted blocks to intravenous tenecteplase (0·25 mg/kg) or alteplase (0·90 mg/kg). The primary outcome was the proportion of patients without disability (modified Rankin Scale 0-1) at 3 months, assessed via masked review in both the intention-to-treat and per-protocol populations. We aimed to recruit 832 participants to yield 90% power (one-sided alpha=0·025) to detect a risk difference of 0·08, with an absolute non-inferiority margin of -0·03. The trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000243718, and the European Union Clinical Trials Register, EudraCT Number 2015-002657-36, and it is completed.
    RESULTS: Recruitment ceased early following the announcement of other trial results showing non-inferiority of tenecteplase versus alteplase. Between March 21, 2014, and Oct 20, 2023, 680 patients were enrolled and randomly assigned to tenecteplase (n=339) and alteplase (n=341), all of whom were included in the intention-to-treat analysis (multiple imputation was used to account for missing primary outcome data for five patients). Protocol violations occurred in 74 participants, thus the per-protocol population comprised 601 people (295 in the tenecteplase group and 306 in the alteplase group). Participants had a median age of 74 years (IQR 63-82), baseline National Institutes of Health Stroke Scale score of 7 (4-11), and 260 (38%) were female. In the intention-to-treat analysis, the primary outcome occurred in 191 (57%) of 335 participants allocated to tenecteplase and 188 (55%) of 340 participants allocated to alteplase (standardised risk difference [SRD]=0·03 [95% CI -0·033 to 0·10], one-tailed pnon-inferiority=0·031). In the per-protocol analysis, the primary outcome occurred in 173 (59%) of 295 participants allocated to tenecteplase and 171 (56%) of 306 participants allocated to alteplase (SRD 0·05 [-0·02 to 0·12], one-tailed pnon-inferiority=0·01). Nine (3%) of 337 patients in the tenecteplase group and six (2%) of 340 in the alteplase group had symptomatic intracranial haemorrhage (unadjusted risk difference=0·01 [95% CI -0·01 to 0·03]) and 23 (7%) of 335 and 15 (4%) of 340 died within 90 days of starting treatment (SRD 0·02 [95% CI -0·02 to 0·05]).
    CONCLUSIONS: The findings in our study provide further evidence to strengthen the assertion of the non-inferiority of tenecteplase to alteplase, specifically when perfusion imaging has been used to identify reperfusion-eligible stroke patients. Although non-inferiority was achieved in the per-protocol population, it was not reached in the intention-to-treat analysis, possibly due to sample size limtations. Nonetheless, large-scale implementation of perfusion CT to assist in patient selection for intravenous thrombolysis in the early time window was shown to be feasible.
    BACKGROUND: Australian National Health Medical Research Council; Boehringer Ingelheim.
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  • 文章类型: Journal Article
    目的:我们的研究旨在评估rt-PA静脉溶栓后卒中患者的血小板计数(PC)与院内转归之间的关系。
    方法:我们确定了2015年6月至2019年7月在中国卒中中心联盟参与医院接受rt-PA静脉溶栓治疗的患者。静脉溶栓前测量的PC分为以下四组:重度血小板减少症(PC<100×109/L),轻度血小板减少症(100≤PC<150×109/L),正常PC(150≤PC≤450×109/L),血小板增多症(PC>450×109/L)。根据住院期间收集的临床数据确定结果。主要临床结果为症状性颅内出血(sICH)。次要结果是死亡率,出血事件,胃肠道(GI)出血,和院内中风复发。我们使用多变量逻辑回归模型来评估PC和结果之间的关联。
    结果:我们包括44,882名患者,中位年龄为66岁,其中34.7%是女性,951(2.1%)患有严重的血小板减少症,7218(16.1%)有轻度血小板减少症,36,522(81.4%)的PC正常,和191(0.4%)有血小板增多症。重度和轻度血小板减少组均有较高的出血事件风险(校正OR1.30;95%CI,1.01-1.67;p=0.045;校正OR1.32;95%CI,1.19-1.46;p<0.001)和sICH(校正OR1.48;95%CI,1.13-1.94;p=0.005;校正OR1.43;95%CI,1.27-1.60;p<0.001)。100≤PC<150×109/L的患者院内卒中复发的风险也较高(校正OR1.12;95%CI,1.02-1.22;p=0.02)。
    结论:在PC<150×109/L的情况下,静脉溶栓会带来sICH的高风险,特别是PC<100×109/L提示PC<100×109/L是溶栓的合理禁忌症。
    OBJECTIVE: Our study aimed to evaluate the associations between platelet count (PC) and in-hospital outcomes for patients with stroke after rt-PA intravenous thrombolysis.
    METHODS: We identified patients who had been hospitalized with a primary diagnosis of stroke and had received rt-PA intravenous thrombolysis from June 2015 to July 2019 at participating hospitals in the Chinese Stroke Center Alliance. PC measured before intravenous thrombolysis was categorized into the following four groups: severe thrombocytopenia (PC < 100 × 109/L), mild thrombocytopenia (100 ≤ PC < 150 × 109/L), normal PC (150 ≤ PC ≤ 450 × 109/L), and thrombocythemia (PC > 450 × 109/L). Outcomes were determined from clinical data collected during hospitalization. The primary clinical outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were mortality, bleeding events, gastrointestinal (GI) hemorrhage, and in-hospital stroke recurrence. We used multivariate logistic regression models to evaluate the associations between PC and outcomes.
    RESULTS: We included 44,882 individuals with a median age of 66 years, of whom 34.7 % were female, 951 (2.1 %) had severe thrombocytopenia, 7218 (16.1 %) had mild thrombocytopenia, 36,522 (81.4 %) had a normal PC, and 191 (0.4 %) had thrombocythemia. Both severe and mild thrombocytopenia groups had higher risks of bleeding events (adjusted OR 1.30; 95 % CI,1.01-1.67; p = 0.045; adjusted OR 1.32; 95 % CI,1.19-1.46; p < 0.001) and sICH (adjusted OR 1.48;95 % CI,1.13-1.94; p = 0.005; adjusted OR 1.43;95 % CI,1.27-1.60; p < 0.001) than the normal PC group. Patients with 100 ≤ PC < 150 × 109/L also had a higher risk of in-hospital stroke recurrence (adjusted OR 1.12; 95 % CI,1.02-1.22; p = 0.02).
    CONCLUSIONS: Intravenous thrombolysis brings a high risk of sICH given PC < 150 × 109/L, especially PC < 100 × 109/L. It indicated that PC < 100 × 109/L is a reasonable contraindication to thrombolysis.
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  • 文章类型: Journal Article
    目的:性别与卒中的临床预后相关。本研究旨在基于抗血小板与重组组织型纤溶酶原激活剂(R-tPA)治疗急性轻度缺血性卒中(ARAMIS)的试验,确定性别对双联抗血小板(DAPT)与阿替普酶治疗缺血性卒中疗效的影响。
    方法:在对ARAMIS研究的二次分析中,在卒中发病4.5h内接受双联抗血小板治疗或静脉注射阿替普酶的18岁或以上轻度非致残性卒中患者被分为两组:男性和女性.主要终点是出色的功能结局,定义为90天时的改良Rankin量表(mRS)0-1。使用二元逻辑回归分析和广义线性模型。
    结果:在完成研究的719名患者中,31%(223)是女性,69%(496)是男性。在出色的功能结局(男性未调整p=0.304,女性p=0.993;男性调整p=0.376,女性p=0.918)和良好的功能结局(mRS评分为0-2;男性未调整p=0.968,女性p=0.881;男性调整p=0.824,女性p=0.881)没有显着的性别差异。但对于次要结果,与阿替普酶相比,DAPT与男性24小时内早期神经系统恶化的比例显著降低相关{未调整比值比[OR]=0.440[95%置信区间(CI),0.221-0.878];p=0.020;调整后的OR=0.436[95%CI,0.216-0.877];p=0.020},但不是女性[未调整OR=0.636(95%CI,0.175-2.319),p=0.490;调整后OR=0.687(95%CI,0.181-2.609),p=0.581]。对于安全结果,与DAPT组相比,阿替普酶与男性出血事件的比例显着增加相关[未调整OR=3.110(95%CI,1.103-8.770);p=0.032],但不是女性[未调整OR=5.333(95%CI,0.613-46.407),p=0.129;调整后OR=5.394(95%CI,0.592-49.112),p=0.135]。
    结论:性别不影响双重抗血小板治疗与阿替普酶静脉治疗对轻度非致残性卒中的效果,但在接受阿替普酶治疗的男性中,早期神经系统恶化和出血事件更多.
    OBJECTIVE: Sex is associated with clinical outcome in stroke. The present study aimed to determine the effect of sex on efficacy of dual antiplatelet (DAPT) versus alteplase in ischemic stroke based on Antiplatelet versus recombinant tissue plasminogen activator (R-tPA) for Acute Mild Ischemic Stroke (ARAMIS) trial.
    METHODS: In this secondary analysis of the ARAMIS study, eligible patients aged 18 years or older with minor nondisabling stroke who received dual antiplatelet therapy or intravenous alteplase within 4.5 h of stroke onset were divided into two groups: men and women. The primary endpoint was an excellent functional outcome, defined as a modified Rankin Scale (mRS) 0-1 at 90 days. Binary logistic regression analyses and generalized linear models were used.
    RESULTS: Of the 719 patients who completed the study, 31% (223) were women, and 69% (496) were men. There were no significant sex differences in excellent functional outcome (unadjusted p = 0.304 for men and p = 0.993 for women; adjusted p = 0.376 for men and p = 0.918 for women) and favorable functional outcome (mRS score of 0-2; unadjusted p = 0.968 for men and p = 0.881 for women; adjusted p = 0.824 for men and p = 0.881 for women). But for the secondary outcomes, compared with alteplase, DAPT was associated with a significantly decreased proportion of early neurological deterioration within 24 h in men {unadjusted odds ratio [OR] = 0.440 [95% confidence interval (CI), 0.221-0.878]; p = 0.020; adjusted OR = 0.436 [95% CI, 0.216-0.877]; p = 0.020}, but not in women [unadjusted OR = 0.636 (95% CI, 0.175-2.319), p = 0.490; adjusted OR = 0.687 (95% CI, 0.181-2.609), p = 0.581]. For the safety outcomes, compared with the DAPT group, alteplase was associated with a significantly increased proportion of any bleeding events in men [unadjusted OR = 3.110 (95% CI, 1.103-8.770); p = 0.032], but not in women [unadjusted OR = 5.333 (95% CI, 0.613-46.407), p = 0.129; adjusted OR = 5.394 (95% CI, 0.592-49.112), p = 0.135].
    CONCLUSIONS: Sex did not influence the effect of dual antiplatelet therapy versus intravenous alteplase in minor nondisabling stroke, but more early neurological deterioration and bleeding events occurred in men who received alteplase.
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  • 文章类型: Journal Article
    早期缺血改变和侧支程度与缺血核心体积(ICV)一致。我们使用Alberta卒中计划早期计算机断层扫描评分和多相计算机断层扫描血管造影(mCTA)侧支范围调查了组合评分之间的关系,命名为mCTA-ACE评分,血管内治疗患者的功能结局。
    我们在2019年12月至2022年1月期间在加拿大22个中心进行的阿替普酶与替奈普酶试验相比,对一组接受血管内治疗的患者进行了事后分析。对应于艾伯塔省卒中计划M2至M6区域的十点mCTA侧支早期计算机断层扫描评分网格评估为0(差),1(中等),或2(正常),并与10点Alberta卒中计划早期计算机断层扫描评分相加,以产生20点mCTA-ACE评分。我们使用混合效应逻辑回归研究了mCTA-ACE评分与改良的Rankin量表评分≤2分以及在90至120天恢复到卒中前功能水平的相关性。在接受基线计算机断层扫描灌注成像的患者中,我们比较了mCTA-ACE评分和ICV的结局预测.
    在该试验的1577名意向治疗人群中,368(23%;179名男性;平均年龄,73年)被包括在内,艾伯塔省卒中计划早期计算机断层扫描评分,mCTA抵押品,两者的组合(mCTA-ACE评分:中位数[四分位数间距],8[7-10],9[8-10],17[16-19]分别)。mCTA-ACE评分每增加1分,改良Rankin量表评分≤2且恢复到卒中前功能水平的概率增加(赔率比,1.16[95%CI,1.06-1.28]和1.22[95%CI,1.06-1.40],分别)。在可评估计算机断层扫描灌注数据的173名患者中,mCTA-ACE评分与ICV呈负相关(ρ=-0.46;P<0.01)。mCTA-ACE评分与ICV相当,可以预测改良的Rankin量表评分≤2,并恢复到卒中前功能水平(C统计学分别为0.71对0.69和0.68对0.64)。
    mCTA-ACE评分与血管内治疗后的功能结局呈显著正相关,并具有与ICV相似的预测性能。
    UNASSIGNED: Early ischemic change and collateral extent are colinear with ischemic core volume (ICV). We investigated the relationship between a combined score using the Alberta Stroke Program Early Computed Tomography Score and multiphase computed tomography angiography (mCTA) collateral extent, named mCTA-ACE score, on functional outcomes in endovascular therapy-treated patients.
    UNASSIGNED: We performed a post hoc analysis of a subset of endovascular therapy-treated patients from the Alteplase Compared to Tenecteplase trial which was conducted between December 2019 and January 2022 at 22 centers across Canada. Ten-point mCTA collateral corresponding to M2 to M6 regions of the Alberta Stroke Program Early Computed Tomography Score grid was evaluated as 0 (poor), 1 (moderate), or 2 (normal) and additively combined with the 10-point Alberta Stroke Program Early Computed Tomography Score to produce a 20-point mCTA-ACE score. We investigated the association of mCTA-ACE score with modified Rankin Scale score ≤2 and return to prestroke level of function at 90 to 120 days using mixed-effects logistic regression. In the subset of patients who underwent baseline computed tomography perfusion imaging, we compared the mCTA-ACE score and ICV for outcome prediction.
    UNASSIGNED: Among 1577 intention-to-treat population in the trial, 368 (23%; 179 men; median age, 73 years) were included, with Alberta Stroke Program Early Computed Tomography Score, mCTA collateral, and combination of both (mCTA-ACE score: median [interquartile range], 8 [7-10], 9 [8-10], and 17 [16-19], respectively). The probability of modified Rankin Scale score ≤2 and return to prestroke level of function increased for each 1-point increase in mCTA-ACE score (odds ratio, 1.16 [95% CI, 1.06-1.28] and 1.22 [95% CI, 1.06-1.40], respectively). Among 173 patients in whom computed tomography perfusion data was assessable, the mCTA-ACE score was inversely correlated with ICV (ρ=-0.46; P<0.01). The mCTA-ACE score was comparable to ICV to predict a modified Rankin Scale score ≤2 and return to prestroke level of function (C statistics 0.71 versus 0.69 and 0.68 versus 0.64, respectively).
    UNASSIGNED: The mCTA-ACE score had a significant positive association with functional outcomes after endovascular therapy and had a similar predictive performance as ICV.
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  • 文章类型: Journal Article
    目的:比较两种治疗黄斑下出血的手术效果和术后并发症,带组织纤溶酶原激活剂(tPA)注射程序的平坦部玻璃体切除术,玻璃体腔注射tPA对黄斑下出血的气压移位。
    方法:对黄斑下出血(SMH)患者进行回顾性分析。数据来自150例黄斑下出血患者。从入院当天到手术后一年对患者进行随访。评估包括视力,光学相干断层扫描(OCT),眼底检查和并发症发生率。
    结果:在小型SMH中,平坦部玻璃体切除术显示出更好的视觉效果。比较两种治疗方式的并发症,在研究中没有发现显著差异。
    结论:平坦部玻璃体切除术和tPA显示出明显的优势,具有更好的视力趋势,并且对于小和中度黄斑下出血具有更好的视力的重要预测指标。
    OBJECTIVE: Comparing between the visual outcomes and post operative complications of two surgical treatments for sub macular hemorrhage, pars plana vitrectomy with tissue plasminogen activator (tPA) injection procedure, and pneumatic displacement of submacular hemorrhage with intravitreal tPA injection.
    METHODS: A retrospective chart review of patients with sub macular hemorrhage (SMH) was performed. Data was collected from 150 patients with sub macular hemorrhage. Patients were followed up from the day of admission and up to a year post surgery. Evaluation included visual acuity, optical coherence tomography (OCT), fundus examination and rates of complications.
    RESULTS: Pars plana vitrectomy procedure has showed a better visual outcome in small SMH. Comparing complications between the two treatment modalities, no significant difference has been found in the study.
    CONCLUSIONS: Pars plana vitrectomy and tPA showed a clear advantage with a trend of better visual acuity as well as a significant predictor to better visual acuity for small and medium sub macular hemorrhage.
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  • 文章类型: Journal Article
    背景:机械血栓切除术(MT)提供的显着临床改善引发了有关大血管闭塞中风中先前静脉溶栓(IVT)的相关性的问题。因此,研究IVT易感性及其对血栓成分的依赖性至关重要。我们使用MT检索的整个血栓的观察性蛋白质组学研究来鉴定与纤维蛋白含量和纤溶活性(FA)相关的因素。方法:在104例脑卒中患者中,通过质谱联用液相色谱建立血栓蛋白质组。通过使用蛋白质组学结合蛋白质电泳评估纤维蛋白原与其纤溶酶切割形式的比率,通过测量血液-血栓界面和内部(FAin)的D-二聚体水平来估计血栓中的FA(FAout)。与纤维蛋白含量相关的因素,通过IVT调整的线性回归确定FAin和FAout。结果:FAout(p<0.0001)和FAin(p=0.0147)由rt-PA给药(47/104)和血栓组成驱动。的确,富含纤维蛋白的患者的FAout高于富含红细胞的血栓,可能是因为更多的(r)t-PA底物。因此,FAout随心源性血栓增加(72/104),富含纤维蛋白(p=0.0300)。在血栓内发现了相反的结果,表明(r)t-PA的渗透性受到纤维帽密度的阻碍。此外,血细胞对血栓结构和对(r)t-PA的易感性有很大影响.的确,纤维蛋白含量与血栓中的红细胞特异性蛋白呈负相关,入院血细胞比容(p=0.0139)和血红蛋白水平(p=0.0080),这强调了红细胞在血栓组成中的关键作用。此外,中性粒细胞受损的FAout数量增加(p=0.0225),这表明它们在血栓周围的聚集阻止了(r)t-PA发作。只有FAout与降低的血栓重量显著相关(p=0.0310),再通率增加(p=0.0150),良好的临床结果(p=0.0480)和降低死亡率(p=0.0080)。结论:蛋白质组学可以为血栓组成与纤溶敏感性之间的密切关系提供新的见解。为新的辅助疗法铺平道路。
    UNASSIGNED: The dramatic clinical improvement offered by mechanical thrombectomy raised questions about the relevance of prior intravenous thrombolysis in large-vessel occlusion strokes. Hence, studying intravenous thrombolysis susceptibility and its dependence on thrombus composition is crucial. We used an observational proteomic study of whole thrombi retrieved by mechanical thrombectomy to identify factors associated with fibrin content and fibrinolytic activity (FA).
    UNASSIGNED: In 104 stroke patients, the thrombi proteome was established by mass spectrometry coupled to liquid chromatography. FA was estimated in clots both outside (FAout) by measuring D-dimer levels at the blood-thrombus interface and inside (FAin) by evaluating the ratio of fibrinogen α to its plasmin-cleaved forms using proteomics coupled with protein electrophoresis. The factors associated with fibrin content, FAin, and FAout were determined by intravenous thrombolysis-adjusted linear regression.
    UNASSIGNED: FAout (P<0.0001) and FAin (P=0.0147) were driven by recombinant tissue-type plasminogen activator (r-tPA) administration (47/104) and thrombus composition. Indeed, FAout was greater with fibrin-rich than erythrocyte-rich thrombi, presumably because of more (r)tPA substrates. Thus, FAout was increased with cardioembolic thrombi (72/104), which are rich in fibrin (P=0.0300). Opposite results were found inside the thrombus, suggesting that (r)tPA penetrability was hampered by the density of the fibrinous cap. Moreover, blood cells had a strong impact on thrombus structure and susceptibility to (r)tPA. Indeed, fibrin content was negatively associated with erythrocyte-specific proteins in the thrombus, admission hematocrit (P=0.0139), and hemoglobin level (P=0.0080), which underlines the key role of erythrocytes in thrombus composition. Also, an increased number of neutrophils impaired FAout (P=0.0225), which suggests that their aggregation around the thrombus prevented the (r)tPA attack. Only FAout was significantly associated with reduced thrombus weight (P=0.0310), increased recanalization rate (P=0.0150), good clinical outcome (P=0.0480), and reduced mortality (P=0.0080).
    UNASSIGNED: Proteomics can offer new insights into the close relationship between thrombus composition and susceptibility to fibrinolysis, paving the way for new adjuvant therapies.
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