The decrease in procarboxypeptidase U (TAFI) concentration in acute ischemic stroke correlates with stroke severity, evolution and outcome

Summary.  Background and objectives:  Procarboxypeptidase U (proCPU, TAFI) concentration in plasma is potentially related to thrombotic tendency, and elevated proCPU levels have been reported in ischemic stroke patients. Improved insight into the role of proCPU in acute ischemic stroke is essential for the development of more adequate therapeutics that may include carboxypeptidase inhibitors. In this study we investigated whether the plasma concentration of proCPU and the proCPU kinetic profile in acute ischemic stroke are related to initial stroke severity, stroke evolution in the subacute phase and long-term stroke outcome. Methods:  Plasma concentration of proCPU was assessed in 136 stroke patients at admission (7.5 h after stroke onset), at 24 h, at 72 h and at day 7 after stroke onset. We evaluated the relation between change in proCPU concentrations and (a) stroke severity (patients with TIA vs. stroke patients, NIHSS score at admission), (b) stroke evolution (stroke progression, infarct volume at 72 h), and (c) stroke outcome (mRS score at month 3). Results:  ProCPU concentration decreased significantly in the first 72 h after stroke onset and thereafter returned to baseline. This biphasic time course, with its nadir at 72 h, was more pronounced in patients with severe stroke, unfavourable stroke evolution in the first 72 h and poor long-term outcome. Conclusions:  The decrease in proCPU concentration in the first 72 h after stroke onset correlates with more severe stroke, unfavourable stroke evolution, and poor long-term stroke outcome.     

Statin pre-treatment is associated with lower platelet activity and favorable outcome in patients with acute non-cardio-embolic ischemic stroke

Introduction

Statins reportedly have anti-inflammatory and anti-thrombotic effects aside from cholesterol-lowering. This study aimed to evaluate the effect of pre-existing statin use on platelet activation markers and clinical outcome in acute ischemic stroke patients.

Methods

This prospective study evaluated 172 patients with acute ischemic stroke divided in two groups: patients with pre-existing statin (n = 43) and without pre-existing statin (66 cases with statins initiated post-stroke and 63 without statin treatment). Platelet activation markers (CD62P and CD63) were measured by flow cytometry at different time points after stroke and analyzed with clinical outcome.

Results

The CD62P and CD63 expressions on platelets were significantly lower in the patients with pre-existing statin use compared to the patients without pre-existing statin use on Day 1 post-stroke (p < 0.05). The CD62P expression was significantly lower in the patients with pre-existing statin use on 90 days after the acute stroke (p < 0.05). Patients with pre-existing statin use had lower incidences of early neurologic deterioration (END) than those without treatment (p < 0.05). Among several baseline clinical variables, admission NIHSS score, history of coronary artery disease, and pre-existing statin use were independent predictions of good clinical outcome at three months.

Conclusions

Pre-existing statin use is associated with decreased platelet activity as well as improved clinical outcome and reduced END in patients with acute ischemic stroke.     

Circulating microparticles and endothelial progenitor cells in atherosclerosis: pharmacological effects of irbesartan

Summary. Aims: This study aimed to (i) employ our newly designed model, the hypertensive–hypercholesterolemic hamster (HH), in order to find out whether a correlation exists between circulating microparticles (MPs), endothelial progenitor cells (EPCs) and their contribution to vascular dysfunction and (ii) to assess the effect of irbesartan treatment on HH animals (HHI).Methods and Results: The results showed that compared with the control (C) group, HH displayed: (i) a significant increase in plasma cholesterol and triglyceride concentration, and an augmentation of systolic and diastolic arterial blood pressure, and of heart rate; (ii) a marked elevation of MPs and a significant decrease in EPCs; (iii) structural modifications of the arterial wall correlated with altered protein expression of MMP2, MMP9, MMP12, TIMP1, TIMP2 and collagen type I and III; (iv) a considerably altered reactivity of the arterial wall closely correlated with MPs and EPC adherence; and (v) an inflammatory process characterized by augmented expression of P‐Selectin, E‐Selectin, von Willebrand factor, tissue factor, IL‐6, MCP‐1 and RANTES. Additionally, the experiments showed the potential of irbesartan to correct all altered parameters in HH and to mobilize EPCs by NO, chemokines and adhesion molecule‐dependent mechanisms.Conclusions: Hypertension associated with hypercholesterolemia is accompanied by structural modifications and expression of pro‐inflammatory molecules by the vessel wall, the alteration of vascular tone, enhanced release of MPs and reduced EPCs; the ratio between the latter two may be considered as a marker of vascular dysfunction. Irbesartan, which exhibits a pharmacological control on the levels of MPs and EPCs, has the potential to restore homeostasis of the arterial wall.     

A new microparticle size calibration standard for use in measuring smaller microparticles using a new flow cytometer

Summary. Background: Microparticle size measurements are often calibrated on flow cytometers using polystyrene microspheres that forward scatter more light vs. particle diameter than cellular microparticles. Methods: We compared theoretical with measured forward angle light scattering on the LSRII, FC500 and Apogee A40 using polystyrene and silica microspheres vs. synthetic lipid vesicles and platelets, then compared plasma microparticle counts using different calibration strategies. Results: Polystyrene and silica microspheres with higher refractive indices forward scattered more light with a wavelength of 488 nm for a given size microparticle than did lipid vesicles or platelets. The LSRII and FC500 did not count many, and were unable to separate by size, polystyrene microspheres < 0.5 μm in diameter. On the Apogee A40, polystyrene microspheres could be separated by size down to 0.2 μm, and a polystyrene microsphere 0.4 μm in diameter produced the same forward scatter relative intensity as a 1‐μm lipid or cellular microparticle. Using the new calibrator, the Apogee A40 found 80 000–4 000 000 μL^?1 total microparticles, 11 000–350 000 μL^?1 annexin V positive microparticles and 6000–350 000 μL^?1 platelet microparticles < 1 μm in plasma samples. Conclusions: The Apogee A40 was able to resolve size differences in polystyrene microspheres down to 0.2 μm and microparticles down to 0.4 μm. On the Apogee A40 we propose using a 0.4‐μm polystyrene microsphere as equivalent to a 1‐μm cellular microparticle for size calibration. Using this calibrator, the Apogee A40 detected higher numbers of total, platelet and annexin V positive microparticles than were found using a Megamix gate.     

急性缺血性脑卒中缺血半暗带的影像学研究进展

急性缺血性脑卒中是临床最常见的脑血管病，具有较高的致死率和致残率。缺血半暗带的存在及对其及时、精准的影像学判断，对于临床治疗方案及时间的合理选择具有重要意义。本文对不同的影像学技术中，急性缺血性脑卒中患者缺血半暗带的研究进展作一综述，以期为缺血半暗带在急性缺血性脑卒中中的应用提供依据，进而提高急性缺血性脑卒中诊断准确率。     

依达拉奉治疗不影响不同尿酸水平急性缺血性卒中患者的预后

目的:探讨依达拉奉治疗急性缺血性卒中患者尿酸水平与90d时临床结局的关系。方法:回顾性研究发病24h内入院的且改良Rankin量表(ModifiedRankinScale,MRS)评分<2的缺血性卒中患者。以尿酸水平中位数值(333μmol/L)作为临界值将患者分为低尿酸(≤333μmol/L)组和高尿酸(>333μmol/L)组,并比较了90d时两组患者的临床资料及良好预后(MRS<2)的关系。进一步研究使用及未使用依达拉奉的尿酸水平与90d时结局指标之间的关系。结果:高尿酸组男性、高血压、心房颤动和心源性卒中的比例高于低尿酸组。高尿酸组90d时MRS<2的患者比例也较高(P=0.013);但在多因素分析中,尿酸与良好结局指标之间无独立相关性(OR1.30,95%CI:0.94~1.71)。在亚组分析中,高尿酸组中未使用依达拉奉治疗的患者90d时MR S<2的人数多于低尿酸组(OR 2.87,95%CI:1.20~7.16),但使用依达拉奉的高尿酸组与低尿酸组患者之间则无相关性。结论:在急性缺血性卒中患者中,依达拉奉治疗后90d时高尿酸水平与良好预后之间的关系不明显。     

Intra-arterial thrombolysis in acute ischemic stroke: a review of pharmacologic approaches

Ischemic stroke is a major public health problem worldwide. The potential to cure stroke patients with intravenous thrombolytic therapy has evolved to the use of intra-arterial thrombolytic agents. Fewer than 200 patients have been enrolled in randomized trials of intra-arterial therapy. In this article the authors have reviewed the literature listed in MEDLINE and EMBase, and searched relevant articles to examine the role of fibrinolytic agents in acute interventional stroke therapy. Only English language articles reporting five or more patients were included. Outcomes were defined at 90 days. Good outcome was defined on the modified Rankin Scale. Symtpomatic hemorrhage was defined as hemorrhage in the setting of clinical deterioration in the first 24 to 48 h. The search identified 57 studies of which 44 reported usable data. Only three randomized trials were reported. Of a total of 1140 patients, most (73%) were treated open-label with urokinase (Abbokinase^®, Abbott Laboratories). The best outcomes were reported in case series and slightly worse outcomes were reported in clinical trials. Overall, it was not possible to distinguish whether one agent was superior to the others. There is a paucity of published evidence on intra-arterial therapy for acute ischemic stroke. Alteplase (Activase^®, Genentech Inc.) is currently the drug of choice simply because it is available and it is the current intravenous standard. Further trials and developments are anticipated.     

Acute ischemic stroke: Relationship of brain lesion location & functional outcome

Purpose. To establish, using brain spiral computerised tomography (SCT) and modified Barthel index (MBI), whether the location of cerebral infarction could be correlated with functional outcome in acute ischemic stroke patients who undergo early intensive rehabilitation.

Methods. Observational cohort, assessor blinded and correlational prospective 12-weeks study that included 111 acute ischemic stroke patients, admitted consecutively to an early intensive inpatient rehabilitation programme (5 days a week, 3–5 h a day) during 2003. Confirmation of diagnosis and stratification was done by brain SCT. Brain lesion locations were correlated to motor performance and functional outcome, on admission and discharge, using MBI.

Results. Statistical analysis demonstrated a significant correlation between motor performance, functional outcome and brain lesion locations. The groups with deep, combined deep and large superficial, small superficial and large superficial infarcts showed the most consistent improvement in that order of frequency. Normal brain SCT group did not reach statistical significance (p = 0.051) while the bi-hemispheric infarcts group did not show any change. The inter and intra group differences were highly significant (p < 0.05).

Conclusions. Immediate non-contrasted brain SCT may act as an independent predictor of final functional outcome in acute ischemic stroke. It may provide clinicians with an opportunity to offer realistic expectations to stroke patients and their relatives.     

Efficacy and safety of human urinary kallidinogenase for acute ischemic stroke: a meta-analysis

ObjectiveHuman urinary kallidinogenase (HUK) is a glycoprotein extracted from human urine that is used to treat stroke by triggering positive regulation of the kallikrein–kinin system. Our aim was to evaluate the efficacy and safety of HUK treatment for acute ischemic stroke.MethodsWe searched the online databases PubMed, Embase, Cochrane Library, Google Scholar, and China National Knowledge Infrastructure (CNKI) for papers published between January 2015 and December 2019. The quality of each trial was assessed using the Cochrane Reviewers’ Handbook. Randomized controlled trials of HUK in patients with acute ischemic stroke were included.ResultsSixteen trials with 1326 participants were included. The HUK injection groups had more neurological improvement than the control groups in National Institutes of Health Stroke Scale scores (mean difference, –1.65; 95% confidence interval [CI], –2.12 to –1.71) and clinical efficacy (1.30; 95% CI, 1.21 to 1.41). Subgroup analysis indicated that age may influence heterogeneity. Eleven trials reported adverse effects and there were no significant differences between the control and HUK groups (risk difference, 0.01; 95% CI, –0.02 to 0.04).ConclusionsHUK ameliorates neurological symptoms in stroke patients with few adverse effects. Further high-quality, large-scale randomized trials are needed to confirm these results.     

循环内皮干细胞与症状性颅内动脉狭窄关系研究

目的研究外周血内皮干细胞（cEPC）数量与颅内动脉狭窄出现及严重度的关系。方法本研究包括了36名颅内动脉狭窄患者（病例组）,40名无脑动脉狭窄卒中患者（病例对照组）和36名健康志愿者（健康对照组）。外周血内皮干细胞基于CD34、CD133和KDR抗原的表达,应用流式细胞仪确定为CD34（＋）CD133（＋）KDR（＋）细胞。结果颅内大动脉狭窄患者外周血内皮干细胞数量显著高于卒中无狭窄患者（P〈0.01）和健康志愿者（P〈0.01）,而卒中无狭窄患者和健康志愿者间内皮干细胞数量差异无统计学差异（P〉0.05）。狭窄率≥70%患者cEPC数量显著高于〈70%患者（0.091±0.035%vs 0.052±0.012%,P〈0.01）。单支狭窄、多支狭窄两组间比较,cEPC数量无显著差异（P〉0.05）。三组中,内皮干细胞数量与纤维蛋白原浓度均无相关性。结论内皮干细胞数量异常增加可能在颅内动脉狭窄发生发展中发挥重要作用。     

低强度氦-氖激光血管内照射对缺血性脑卒中患者血管内皮功能的影响

目的：探讨低强度氦－氖激光血管内照射疗法（ILLI）对缺血性脑卒中患者血管内皮功能的影响。方法：将48例缺血性脑卒中患者随机分为常规组和ILLI治疗组，ILLI治疗组在常规治疗组的基础上加用ILLI疗效。两组病人均于入院的次日及第29天应用高分辨率超声检测肱动脉流量介导的舒张活性（FMD）变化。结果：经四周的治疗后，两组的FMD值均较各自治疗前显著升高，但ILLI组的FMD升高较常规组更为显著。结论：低强度氦－氖激光血管内照射疗法能有效改善缺血性脑卒中患者的血管内皮功能。     

Case report of male child with elevated lipoprotein (a) leading to acute ischemic stroke

Acute ischemic stroke (AIS) in children is rare with almost 40% diagnosed as cryptogenic. One possible mechanism associated with AIS is an elevated Lipoprotein (a) [Lp(a)] level. Here, we discuss the case of an 11‐year old boy who presented with multiple thrombotic strokes secondary to elevated Lp(a), which was identified as the only risk factor and immediately treated with lipoprotein apheresis (LA). Eighteen months post‐AIS, he is still receiving LA treatments and has made remarkable progress in his recovery without another cerebrovascular event.     

代谢综合征与急性脑梗死患者预后的关系

目的探讨代谢综合征与急性脑梗死患者预后之间的关系。方法观察自2008年1月至2014年1月691例急性脑梗死患者,按照1995年全国第4届脑血管病学术会议《临床疗效评定标准》进行预后评定,运用多因素回归分析评估代谢综合征与急性脑梗死患者预后之间的关系。结果 691例患者中,277例患者预后较差,代谢综合征与急性脑梗死预后之间联系显著,校正OR值(95%CI)为1.57(1.13~2.19),不良预后与代谢综合征包含的危险因素数量之间关系显著。结论代谢综合征与急性脑梗死不良预后关系显著。     

AIS患者静脉溶栓过程中的血栓弹力图与凝血试验的比较

目的观察急性缺血性脑梗死(AIS)患者瑞通立静脉溶栓过程中血栓弹力图(TEG)和凝血指标的变化。方法选取2013年10月至2015年8月在聊城市第三人民医院住院的AIS患者43例,从发病到溶栓治疗时间在4.5 h内,并在溶栓前及溶栓后0.5、1、2、4 h,采集其静脉血进行凝血和TEG分析。结果在瑞通立静脉溶栓过程中,TEG测定参数的凝血因子激活时间(R)、血块形成速率参数(K)、弹力图最大切角(α-Angle)、弹力图最大振幅(MA)和凝血指标均发生变化。溶栓后0.5 h活化部分凝血活酶时间(APTT)与溶栓前比较,差异有统计学意义(P0.01),凝血酶原时间(PT)、凝血酶时间(TT)、D-二聚体(D-D)、纤维蛋白(原)降解产物(FDP)溶栓后2 h均达最高。溶栓后0.5 h R较溶栓前增高,溶栓后1 h达高值;K在溶栓后0.5 h达高值;α-Angle和MA在溶栓后0.5 h达低值;R、K溶栓后1 h与溶栓前比较,差异有统计学意义(P0.01);α-Angle和MA溶栓后0.5 h分别与溶栓前比较,差异均有统计学意义(P0.01)。结论在瑞通立静脉溶栓过程中TEG动态检测是判断凝血状态的有用工具。     

纳洛酮对急性缺血性中风神经功能的保护作用

目的 :观察加用纳洛酮治疗急性缺血性中风的效果。方法 :采用随机对照研究的方法 ,对急性缺血性中风后 72 h内入院 ,经头颅 CT或 MRI证实符合临床表现及相应影像学改变的患者 ,按诊断标准分成腔隙性和非腔隙性脑梗死两类 ,将非腔隙性脑梗死又分为轻型〔美国国立卫生院卒中量表评分 (NIHSS<8)〕及重型(NIHSS≥ 8)。在入院时及治疗 4周时行 NIHSS和改良 Rankin评分 (MRS)。对照治疗组给予尼莫地平或脑益嗪、脑复康、都可喜等常规脑保护剂药物 ;纳洛酮组加用盐酸纳洛酮注射液 1.6～ 2 .0 mg/ d静脉滴注 ,疗程3～ 4周 ;两组均根据病情给予常规抗凝、降纤、稀释或抗血小板聚集等治疗。结果 :16 8例患者入选 ,纳洛酮组71例 ,对照组 97例。纳洛酮组和对照治疗组治疗后神经功能缺损均有改善 ,但在腔隙性脑梗死患者中 ,加用纳洛酮并不比常规治疗更能有效地改善神经功能缺损的程度。在轻型非腔隙性脑梗死患者中 ,加用纳洛酮较对照治疗更能显著降低神经功能缺损评分的 NIHSS值 ,但 MRS差值与对照治疗组间差异无显著性 ;在重型非腔隙性脑梗死患者中 ,加用纳洛酮与对照治疗组相比能显著地降低 NIHSS及 MRS值。结论 :纳洛酮作为一种新型的脑保护剂可以显著改善脑梗死患者神经功能缺损程度 ,减轻残疾 ,对重症、神经功能     

急性缺血性脑卒中患者介入治疗时所受的辐射剂量的影响因素

目的分析急性缺血性脑卒中患者在介入诊疗中的受照剂量,探讨性别、年龄、病变部位以及诊疗方式等因素对辐射剂量的影响。方法回顾性分析我院行介入治疗的急性缺血性脑卒中患者156例,最终纳入113例,随机配置的辐射监测系统记录透视时间（FT）、剂量面积乘积（DAP）、空气比释动能（AK）。分析性别、患者年龄（30~60岁组、60~80岁组、≥80岁组）、闭塞位置（前、后循环）以及血管开通技术对患者受照剂量的影响。结果患者FT值7.94~97.41 min（24.0±14.4 min）;DAP值1638~551959 mGy·cm²（137 422.8±107 778.1 mGy·cm²）;AK值11~5726 mGy（1210.9±1070.8 mGy）。男性患者辐射剂量高于女性患者,DAP值、AK值差异有统计学意义（P＜0.05）;3个年龄组间各剂量值差异均无统计学意义（P>0.05）;前、后循环闭塞患者所受剂量差异无统计学意义（P>0.05）;单纯导管抽吸（ASPI）患者辐射剂量最低,导管抽吸结合支架取栓（ASPI+SR）以及支架植入术组的辐射剂量大于ASPI组,3个剂量值差异均有统计学意义（P＜0.05）。结论急性缺血性脑卒中患者所受辐射剂量差异较大,性别、血管开通方式均是影响辐射剂量的重要因素。因此,可能需要针对不同特征的患者采取更积极的防护措施。     

血浆细胞纤维连接蛋白动态检测在急性脑梗死预后判断中的价值

目的 探讨血浆细胞纤维连接蛋白(c-Fn)在急性脑梗死中的动态变化及其在预后判断中的意义.方法 采用酶联免疫吸附法动态检测66例急性脑梗死患者及40名正常对照者血浆c -Fn水平,根据美国国立卫生院神经功能缺损评分,分析其与病情和预后的相关性.并通过受试者工作特征(ROC)曲线判断预测急性脑梗死的血浆c-Fn最佳临界值.结果 急性脑梗死组入院时(24 h内)血浆c-Fn含量较对照组明显升高,差异有统计学意义(t=7.03,P＜0.05),随着病情变化c-Fn含量于伤后3～14 d出现逐渐降低、持续高值或继发性升高;预后不良组血浆c-Fn含量明显高于预后良好组,差异有统计学意义(t=5.46,P＜0.05),根据ROC曲线,初步得出血浆c-Fn浓度＞5.24μg/ml可作为预测急性脑梗死预后的临界值.结论 外周血血浆c-Fn水平变化情况有助于观察脑梗死患者病情的动态变化和判断预后.     

Glycemia management in acute ischemic stroke: current concepts and novel therapeutic targets

Hyperglycemia on hospital admission is a common phenomenon in acute ischemic stroke patients and represents an independent predictor of poor clinical outcome with or without acute recanalization therapies (systemic thrombolysis or mechanical thrombectomy). Effective restoration of normoglycemia is considered to be beneficial, but conclusive evidence from randomized controlled clinical trials and specific recommendations are lacking. In addition, aggressive glucose control can be complicated by hypoglycemia leading to early neurological deterioration. We conducted a systematic literature review with the aim of addressing several questions: timing of glucose control, target range, type of insulin delivery, duration and practicability of glucose-lowering protocols. Special issues regarding mechanical thrombectomy and glycemic variability can then be investigated in future trials which are also being considered.