阿司匹林对骨髓间充质干细胞移植治疗缺血性脑卒中的影响研究进展

阿司匹林是缺血性脑卒中患者急性期治疗药物及卒中再发的二级预防常用药物,骨髓间充质干细胞(BMSCs)移植是治疗缺血性脑血管疾病的新的新兴技术。已证实阿司匹林可抑制骨髓间充质干细胞的增殖及影响骨髓间充质干细胞的分化。本文就阿司匹林对骨髓间充质干细胞移植治疗缺血性脑卒中的影响等进行综述。     

进展性缺血性卒中预后的相关因素分析

目的:探究进展性缺血性卒中预后的相关危险因素。方法:选取进展性缺血性卒中患者98例,根据复发情况将患者分为复发组和无复发组,分析进展性缺血性卒中复发与二级预防的关系。无复发组的患者按根据随访的mRS评分高低分为:预后良好组(mRS 0~2分)和预后差组(mRS 3~5分),分析影响预后的相关因素。结果:98例进展性缺血性卒中患者六个月复发率为10.2%(10/98)。无复发组较复发组应用降压药、降糖药、抗血小板聚集药物、他汀类降脂药的患者比例较复发组高,两组比较差异均具有统计学意义(P0.05)。无复发组患者出院后一个月、三个月及六个月,单因素分析入院时白细胞计数、LDL、血糖与预后相关(P0.05)。多因素logistic回归分析LDL、血糖和白细胞计数是影响出院后一个月预后的危险因素;血糖和白细胞计数是影响出院后三个月预后的危险因素;LDL和血糖是影响出院后六个月预后的危险因素。结论:良好的二级预防依从性有利于降低进展性缺血性卒中的复发率。入院时白细胞计数、LDL、血糖是影响进展性缺血性卒中预后的相关因素。入院时白细胞计数、LDL及空腹血糖值较高的进展性缺血卒中患者,其预后往往较差。     

缺血性脑卒中二级预防研究进展

脑卒中具有发病率高、致残率高、复发率高、病死率高、治疗效果差的"四高一低"特点,是一种严重危害人类健康的全球性问题,被称为人类健康的第一号杀手!随着医学的进步,卒中死亡率下降,卒中复发率随之增加。然而,脑卒中是可预防性疾病,有效地预防措施不仅可以降低脑卒中的复发率,而且能降低与脑卒中有关的医疗费用,减轻家庭与社会的经济负担,因此,脑卒中的预防已成为世界各国研究的热点和焦点。本文就脑卒中二级预防做一综述。     

缺血性脑卒中二级预防研究进展

脑卒中具有发病率高、致残率高、复发率高、病死率高、治疗效果差的“四高一低”特点,是一种严重危害人类健康的全球性问题,被称为人类健康的第一号杀手!随着医学的进步,卒中死亡率下降,卒中复发率随之增加.然而,脑卒中是可预防性疾病,有效地预防措施不仅可以降低脑卒中的复发率,而且能降低与脑卒中有关的医疗费用,减轻家庭与社会的经济负担,因此,脑卒中的预防已成为世界各国研究的热点和焦点.本文就脑卒中二级预防做一综述.     

普伐他汀联合阿司匹林治疗老年缺血性脑卒中的疗效及对血脂和认知功能的影响

目的:探讨普伐他汀联合阿司匹林对老年缺血性脑卒中的治疗疗效及其对患者血脂和认知功能的影响。方法:选择我院80例老年缺血性脑卒中患者,按入院顺序采用随机数字表法平均分为两组各40例,两组患者均给予常规缺血性脑卒中对症治疗,研究组患者在此基础上使用普伐他汀联合阿司匹林治疗,对照组患者仅使用阿司匹林治疗。比较两组患者治疗疗效,同时比较两组患者血清中血脂水平及认知功能改变情况。结果:研究组患者总治疗有效率为92.5%,明显高于对照组65%,比较差异具有统计学意义(P0.05);研究组患者治疗后血脂水平较治疗前明显下降,且下降程度显著高于对照组,比较差异具有统计学意义(P0.05);研究组患者治疗后认知功能评分总分为(93.75±11.45)分,明显高于对照组(84.11±12.04)分,比较差异具有统计学意义(P0.05)。结论:普伐他汀联合阿司匹林对老年缺血性脑卒中的治疗疗效显著,可有效改善患者血脂水平和认知功能,值得推广应用。     

蒺藜总皂苷对缺血性脑卒中患者血清C反应蛋白及血液流变学的影响

目的:观察蒺藜总皂苷(GSTT)对缺血性脑卒中患者血清C-反应蛋白(CRP)及血液流变学的影响.方法:本研究采用前瞻性开放性病例对照研究,将103例急性缺血性脑卒中患者随机分为治疗组和对照组:对照组(50例)采用常规治疗;治疗组(53例)在常规治疗的基础上加GSTT(30mg/次,一日三次)口服,于治疗前以及治疗28 d后检测患者CRP及血液流变学指标.结果:两组患者治疗后CRP均低于治疗前,差异有显著性(P＜0.01);GSTT可显著降低全血黏度、血浆黏度、纤维蛋白原水平,与治疗前比,差异有显著性(P＜0.05).结论:急性缺血性脑卒中患者血清CRP增高,血液流变学指标异常,GSTT可降低其CRP,改善血液流变学指标.     

GSK-3β对缺血性脑卒中病理过程调控作用的研究进展

糖原合成酶激酶-3β(glycogen synthase kinase-3β,GSK-3β)作为机体最重要的激酶之一,广泛地参与了缺血性脑卒中的病理过程。因此,正确认识脑卒中后GSK-3β的功能并加以利用,由此寻求减轻组织损伤和改善神经功能的方法是提高脑卒中治疗的重要途径。该文就GSK-3β对缺血性脑卒中后的氧化应激、炎症、自噬、凋亡等病理过程的调控机制进行综述,为缺血性脑卒中提供新的研究方向和潜在的临床治疗靶点。     

长链非编码RNA调节缺血性脑卒中损伤和修复的研究进展

长链非编码RNA(long noncoding RNA,lnc RNA)是一组在转录、转录后和表观遗传水平发挥作用的调控序列,其在中枢神经系统中特异性高表达,对中枢神经系统发育和疾病发展具有重要调控作用。缺血性脑卒中诱导脑内大量lnc RNA表达改变,提示lnc RNA与缺血性脑卒中复杂的病理过程有关,这将有利于全面认识缺血性脑卒中的病理机制及脑缺血损伤后的分子调控网络,并提供新的治疗方向。尽管有少数研究报道lnc RNA在缺血性心脏病中的作用,但目前对于其在缺血性脑卒中病理发展中的作用知之甚少。综述目前已知的lnc RNA在脑缺血再灌注损伤、细胞凋亡与抗凋亡及损伤后神经再生与修复中的作用,并提出了未来可能的lnc RNA在缺血性脑卒中损伤与修复中的研究方向。     

阿斯匹林治疗急性缺血性脑卒中临床疗效随机双盲对照研究

目的 探讨阿斯匹林抗血小板治疗急性缺血性脑卒中,对降低死亡率,改善致残率的临床疗效。方法 采取随机、双盲、安慰剂对照,对发病48h内的急性缺血性脑卒中患者,均经头颅CT检查排除出血性脑卒中。入选患者在常规治疗的基础上,口服阿斯匹林,每天160mg或安慰剂4周。结果 服阿斯匹林的患者（阿斯匹林组）和服安慰剂的患者（安慰剂组）相比较,两组对降低死亡率,减轻致残率的结果差异无统计学意义（P＞0．05）。结论 在常规治疗急性缺血性脑卒中的基础上,加服阿斯匹林160mg对降低病死率和出院时的致残率效果不明显。     

中西医结合治疗对急性缺血性脑卒中患者TNF-α,hs-CRP,IL-6和神经功能的影响

目的:研究中西医结合治疗对急性缺血性脑卒中患者血清肿瘤坏死因子(TNF-α)、高敏反应蛋白(hs-CRP)、白细胞介素-6(IL-6)和神经功能的影响。方法:选择2010年2月~2015年12月我院急性缺血性脑卒中患者81例,随机分为两组。对照组静脉滴注低分子右旋糖苷、丹红、胞磷胆碱,观察组联合口服益气活血、醒脑涤痰中药汤剂。分别在治疗前和治疗14 d后,检测血清TNF-α、hs-CRP、IL-6水平,并用美国国立卫生研究院卒中量表(NIHSS)对神经功能进行评价。结果:观察组的有效率明显高于对照组(P0.05);两组治疗后TNF-α、hs-CRP和IL-6水平均明显降低(P0.05),且观察组明显更低(P0.05);两组治疗后NIHSS评分均明显降低(P0.05),且观察组明显更低(P0.05)。结论:中西医结合治疗能降低急性缺血性脑卒中患者TNF-α、hs-CRP、IL-6水平,明显改善患者神经功能。     

The Rx for Change database: a first-in-class tool for optimal prescribing and medicines use

Background

Survivors of transient ischemic attack (TIA) or stroke are at high risk for recurrent vascular events and aggressive treatment of vascular risk factors can reduce this risk. However, vascular risk factors, especially hypertension and high cholesterol, are not managed optimally even in those patients seen in specialized clinics. This gap between the evidence for secondary prevention of stroke and the clinical reality leads to suboptimal patient outcomes. In this study, we will be testing a pharmacist case manager for delivery of stroke prevention services. We hypothesize this new structure will improve processes of care which in turn should lead to improved outcomes.

Methods

We will conduct a prospective, randomized, controlled open-label with blinded ascertainment of outcomes (PROBE) trial. Treatment allocation will be concealed from the study personnel, and all outcomes will be collected in an independent and blinded manner by observers who have not been involved in the patient's clinical care or trial participation and who are masked to baseline measurements. Patients will be randomized to control or a pharmacist case manager treating vascular risk factors to guideline-recommended target levels. Eligible patients will include all adult patients seen at stroke prevention clinics in Edmonton, Alberta after an ischemic stroke or TIA who have uncontrolled hypertension (defined as systolic blood pressure (BP) > 140 mm Hg) or dyslipidemia (fasting LDL-cholesterol > 2.00 mmol/L) and who are not cognitively impaired or institutionalized. The primary outcome will be the proportion of subjects who attain 'optimal BP and lipid control'(defined as systolic BP < 140 mm Hg and fasting LDL cholesterol < 2.0 mmol/L) at six months compared to baseline; 12-month data will also be collected for analyses of sustainability of any effects. A variety of secondary outcomes related to vascular risk and health-related quality of life will also be collected.

Conclusions

Nearly one-quarter of those who survive a TIA or minor stroke suffer another vascular event within a year. If our intervention improves the provision of secondary prevention therapies in these patients, the clinical (and financial) implications will be enormous.     

The NAILED stroke risk factor trial (Nurse based Age independent Intervention to Limit Evolution of Disease after stroke): study protocol for a randomized controlled trial

Background

Secondary prevention after stroke and transient ischemic attack (TIA) is essential in order to reduce morbidity and mortality. Secondary stroke prevention studies have, however, been fairly small, or performed as clinical trials with non-representative patient selection. Long-term follow-up data is also limited. A nurse-led follow-up for risk factor improvement may be effective but the evidence is limited. The aims of this study are to perform an adequately sized, nurse-led, long-term secondary preventive follow-up with a population-based inclusion of stroke and TIA patients. The focus will be on blood pressure and lipid control as well as tobacco use and physical activity.

Methods

A randomized, controlled, long-term, population-based trial with two parallel groups. The patients will be included during the initial hospital stay. Important outcome variables are sitting systolic and diastolic blood pressure, LDL cholesterol and total cholesterol. Outcomes will be measured after 12, 24 and 36 months of follow-up. Trained nurses will manage the intervention group with a focus on reaching set treatment goals as soon as possible. The control group will receive usual care. At least 200 patients will be included in each group, in order to reliably detect a difference in mean systolic blood pressure of 5 mmHg. This sample size is also adequate for detection of clinically meaningful group differences in the other outcomes.

Discussion

This study will test the hypothesis that a nurse-led, long-term follow-up after stroke with a focus on reaching set treatment goals as soon as possible, is an effective secondary preventive method. If proven effective, this method could be implemented in general practice at a low cost.

Trial registration

Current Controlled Trials ISRCTN23868518     

Current and future concepts in stroke prevention

STROKE IS A MAJOR CAUSE OF MORBIDITY and mortality in an aging population. The current understanding of the pathophysiology of atherosclerotic diseases, the most common cause of stroke, and the evidence for existing therapeutic interventions for the prevention of stroke are presented. Specifically, we review the evidence for antiplatelet agents, anticoagulants, antihypertensive medications, lipid-lowering agents and carotid endarterectomy for stroke prevention. Each year in Canada stroke occurs in 50 000 people and accounts for 7% of all deaths. Canada''s population of stroke survivors numbers almost 300 000, of whom 30% remain permanently disabled.^1,2,3 Care for stroke patients accounts for 2.1% of Canadian health care expenditures.⁴ Primary prevention of a first stroke and secondary prevention of recurrent events require rapid identification of risk factors and implementation of appropriate preventive measures.The risk of stroke following an initial cerebrovascular event is high. Of patients presenting to an emergency department with a transient ischemic attack (TIA), 10.5% will have a stroke (half of these occurring in the first 2 days) and 2.6% will die within 90 days.⁵ Overall, 8.8% of stroke survivors will have a recurrent stroke within the first 6 months, and 15% within 5 years.⁶ In most cases (about 50%) the stroke is atherothrombotic in origin, with a further 25% attributable to small-vessel lacunar disease and 20% to cardioembolism. Data from a stroke registry reveal that patients who have an atherothrombotic stroke have the highest rates of recurrence within 30 days (18.5%), as compared with those who have a lacunar (1.4%) or cardioembolic (5.3%) stroke.⁷In this review we present the current understanding of the pathophysiology of atherosclerotic disease, the most common cause of stroke. We also provide an overview of the available evidence for common therapeutic interventions used for stroke prevention: antiplatelet agents, anticoagulants, antihypertensive medications, lipid-lowering agents and carotid endarterectomy.     

Biomarkers and perfusion – training-induced changes after stroke (BAPTISe): protocol of an observational study accompanying a randomized controlled trial

Background

Physical activity is believed to exert a beneficial effect on functional and cognitive rehabilitation of patients with stroke. Although studies have addressed the impact of physical exercise in cerebrovascular prevention and rehabilitation, the underlying mechanisms leading to improvement are poorly understood. Training-induced increase of cerebral perfusion is a possible mediating mechanism. Our exploratory study aims to investigate training-induced changes in blood biomarker levels and magnetic resonance imaging in patients with subacute ischemic stroke.

Methods/design

This biomarker-driven study uses an observational design to examine a subgroup of patients in the randomized, controlled PHYS-STROKE trial. In PHYS-STROKE, 215 patients with subacute stroke (hemorrhagic and ischemic) receive either 4 weeks of physical training (aerobic training, 5 times a week, for 50 minutes) or 4 weeks of relaxation sessions (5 times a week, for 50 minutes). A convenience sample of 100 of these patients with ischemic stroke will be included in BAPTISe and will receive magnetic resonance imaging (MRI) scans and an additional blood draw before and after the PHYS-STROKE intervention. Imaging scans will address parameters of cerebral perfusion, vessel size imaging, and microvessel density (the Q factor) to estimate the degree of neovascularization in the brain. Blood tests will determine several parameters of immunity, inflammation, endothelial function, and lipometabolism. Primary objective of this study is to evaluate differential changes in MRI and blood-derived biomarkers between groups. Other endpoints are next cerebrovascular events and functional status of the patient after the intervention and after 3 months assessed by functional scores, in particular walking speed and Barthel index (co-primary endpoints of PHYS-STROKE). Additionally, we will assess the association between functional outcomes and biomarkers including imaging results. For all endpoints we will compare changes between patients who received physical fitness training and patients who had relaxation sessions.

Discussion

This exploratory study will be the first to investigate the effects of physical fitness training in patients with ischemic stroke on MRI-based cerebral perfusion, pertinent blood biomarker levels, and functional outcome. The study may have an impact on current patient rehabilitation strategies and reveal important information about the roles of MRI and blood-derived biomarkers in ischemic stroke.

Trial registration

NCT01954797.

     

Cognitive State following Stroke: The Predominant Role of Preexisting White Matter Lesions

Background and purpose

Stroke is a major cause of cognitive impairment and dementia in adults, however the role of the ischemic lesions themselves, on top of other risk factors known in the elderly, remains controversial. This study used structural equation modeling to determine the respective impact of the new ischemic lesions'' volume, preexisting white matter lesions and white matter integrity on post stroke cognitive state.

Methods

Consecutive first ever mild to moderate stroke or transient ischemic attack patients recruited into the ongoing prospective TABASCO study underwent magnetic resonance imaging scans within seven days of stroke onset and were cognitively assessed one year after the event using a computerized neuropsychological battery. The volumes of both ischemic lesions and preexisting white matter lesions and the integrity of the normal appearing white matter tissue were measured and their contribution to cognitive state was assessed using structural equation modeling path analysis taking into account demographic parameters. Two models were hypothesized, differing by the role of ischemic lesions'' volume.

Results

Structural equation modeling analysis of 142 patients confirmed the predominant role of white matter lesion volume (standardized path coefficient β = −0.231) and normal appearing white matter integrity (β = −0.176) on the global cognitive score, while ischemic lesions'' volume showed no such effect (β = 0.038). The model excluding the ischemic lesion presented better fit to the data (comparative fit index 0.9 versus 0.092).

Conclusions

Mild to moderate stroke patients with preexisting white matter lesions are more vulnerable to cognitive impairment regardless of their new ischemic lesions. Thus, these patients can serve as a target group for studies on cognitive rehabilitation and neuro-protective therapies which may, in turn, slow their cognitive deterioration.     

Statins in prevention and treatment of ischemic stroke

Based on the published data, including the results of large-scale, randomized, placebo-controlled trials, the article presents current strategies for the use of statins in primary and secondary prevention of ischemic stroke. Special attention is paid to the efficacy and advanced applications of statins in acute stroke. Based on the gross data, recommendations for the use of statins in prevention and treatment of ischemic stroke are presented.     

The efficacy and safety of cilostazol for the secondary prevention of ischemic stroke in acute and chronic phases in Asian population- an updated meta-analysis

Backgrounds

While previous meta-analysis have investigated the efficacy of cilostazol in the secondary prevention of ischemic stroke, they were criticized for their methodology, which confused the acute and chronic phases of stroke. We present a new systematic review, which differs from previous meta-analysis by distinguishing between the different phases of stroke, and includes two new randomized, controlled trials (RCTs).

Methods

All RCTs investigating the effect of cilostazol on secondary prevention of ischemic stroke were obtained. Outcomes were analyzed by Review Manager, including recurrence of cerebral infarction (ROCI), hemorrhage stroke or subarachnoid hemorrhage (HSSH), all-cause death (ACD), and modified Rankin Scale score (mRS). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessed the quality of the evidence.

Results

5491 patients from six studies were included in the current study. In secondary prevention of ischemic stroke in chronic phase, cilostazol was associated with a 47% reduction in ROCI (relative risk [RR] 0.53, 95% confidence interval [CI] 0.34 to 0.81, p?=?0.003), while no significant difference in HSSH and ACD compared with placebo; and 71% reduction in HSSH (RR 0.29, 95% CI 0.15 to 0.56, p?=?0.0002) compared with aspirin, but not in ROCI and ACD. In the secondary prevention of ischemic stroke in acute phase, cilostazol did not show any effect in the ROCI, HSSH, ACD and mRS compared to placebo or aspirin. The quality of the evidence from chronic phase was high or moderate, and those from acute phase were moderate or low when analyzed by GRADE approach.

Conclusion

Cilostazol provided a protective effect in the secondary prevention of the chronic phase of ischemic stroke.

     

Effects of living with and looking after survivors of a stroke.

Information from a two year, longitudinal study on a community sample of patients with acute stroke was analysed to determine the effects of the stroke on the mood of the chief carer (the person living with the patient). Increased anxiety was the most commonly reported change six months after stroke. Significant depression was seen in 11-13% of carers over the first two years after stroke. The patient''s functional disability was associated with depression in the carer over the first year but not at two years. A perceived poor recovery by the patient, a low level of general activities by the patient, and depression in the patient were also associated with depression in the carer within the first year. At two years after stroke none of the measured factors were related to a carer''s level of depression. Carers of patients who have suffered stroke showed anxiety and emotional distress unrelated to the patient''s physical disability after two years. More help from stroke support groups for carers is perhaps needed.