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Relationship between high levels of D-dimer and prognosis in patients with spontaneous supratentorial cerebral haemorrhage: A retrospective study and double validation 自发性脑室上出血患者高水平 D-二聚体与预后之间的关系:一项回顾性研究和双重验证。
IF 2 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-11-10 DOI: 10.1016/j.jstrokecerebrovasdis.2024.108129
ZhenKun Xiao PhD , Xingyu Mao MS , Bing Wang PhD , YiBo Yang MS , Jie Niu MD , Yong-Mei Yang PhD , Ai-Hua Liu PhD , Yong-Hong Duan MD

Objective

The aim of this study was to investigate the correlation between D-Dimer and unfavorable outcome after surgery for spontaneous supratentorial intracerebral hemorrhage(SSICH)

Methods

A total of 557 patients with spontaneous supratentorial intracerebral hemorrhage underwent surgical treatment, which included craniotomy evacuation of hematoma and puncture and drainage. Based on the modified Rankin Scale (mRS) bifurcation, the patients were divided into two subgroups: favorable outcome (mRS score 0–2) and unfavorable outcome (mRS score 3-5). D-dimer levels were measured within 24 h of admission, monitored until discharge, and grouped by quartiles (Q1-Q4). We collected and calculated D-dimer levels at different periods of time: (1) at admission (pre-surgery); (2) average post-surgery level; (3) average level during hospitalization; and (4) peak level during hospitalization. Two methods were used for validation, the first using a traditional multifactorial Logsitic regression equation, and the second where we chose baseline clinical, laboratory, and other variables and constructed a prognostic model through multivariate logistic regression.

Results

Statistical results showed statistically significant differences in age, Glasgow Coma Score (GCS) on admission, high levels of D-dimer, and bleeding. Predictive models developed on the basis of initial age, GCS, and D-Dimer showed good discriminatory power

Conclusions

D-dimer is an independent risk factor for the development of poor postoperative prognosis in patients with SSTICH, and a prognostic model developed on the basis of D-Dimer predicts the development of poor postoperative prognosis in patients with SSTICH. The model needs to be validated in larger studies conducted at other institutions.
研究目的方法:557 例自发性幕上脑室内出血患者接受了手术治疗,包括开颅手术清除血肿和穿刺引流。根据改良Rankin量表(mRS)的分叉,患者被分为两个亚组:预后良好组(mRS评分0-2分)和预后不良组(mRS评分3-5分)。在入院 24 小时内测量 D-二聚体水平,监测直至出院,并按四分位数(Q1-Q4)分组。我们收集并计算了不同时期的 D-二聚体水平:(1) 入院时(手术前);(2) 手术后的平均水平;(3) 住院期间的平均水平;(4) 住院期间的峰值水平。我们采用了两种方法进行验证,第一种是使用传统的多因素 Logsitic 回归方程,第二种是选择基线临床、实验室和其他变量,通过多变量 Logistic 回归构建预后模型:统计结果表明,年龄、入院时格拉斯哥昏迷评分(GCS)、D-二聚体水平高和出血量在统计学上存在显著差异。根据初始年龄、GCS 和 D-二聚体建立的预测模型显示出良好的判别能力 结论:D-二聚体是一个独立的风险因素:D-二聚体是导致 SSTICH 患者术后预后不良的独立危险因素,根据 D-二聚体建立的预后模型可预测 SSTICH 患者术后预后不良的情况。该模型需要在其他机构进行的更大规模研究中得到验证。
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引用次数: 0
Perception and acquaintance of stroke specialists on non-inferiority trials: An international survey 非劣效性试验中卒中专家的认识和了解:一项国际调查。
IF 2 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-11-10 DOI: 10.1016/j.jstrokecerebrovasdis.2024.108132
Aristeidis H. Katsanos MD , Vasileios-Arsenios Lioutas MD , Laetitia Yperzeele MD , Teresa Ullberg MD , Linxin Li MD , Emily R. Ramage PhD , Ivan A. Koltsov MD, PhD , Julia Shapranova MSc , George Howard DrPH , Philip M. Bath FMedSci , Maria Khan MD , World Stroke Organization Future Leaders

Introduction

The adoption of non-inferiority trial designs for assessing new interventions in stroke treatment is on the rise. We designed a survey to assess stroke specialists' understanding and familiarity with non-inferiority trials and margins.

Methods

A brief web-based questionnaire was sent to the members of the World Stroke Organization (WSO). The median acceptable non-inferiority margins in different research settings provided by responders were summarized and reported according to the acquaintance of responders with non-inferiority trials.

Results

A total of 120 WSO members from 42 countries responded to the survey. Thirty-two percent (32 %) of respondents self-identified as being very familiar with non-inferiority trials, while 6 % identified as extremely familiar. When asked about the impact of non-inferiority trials on improving stroke patient care, 42 % rated it as high and 45 % as moderate. 83 % of responders reported that the findings of non-inferiority trials affect their clinical practice. Ease of administration, relative effect of the standard treatment, clinical implications of inappropriately introducing the new treatment, availability, price, ease of storage and shipping were all considered as factors that should influence the size of the non-inferiority margin. The magnitude and variability of acceptable non-inferiority margins were seen to decrease as the acquaintance of responders with non-inferiority trials increased.

Conclusion

Although responders acknowledge the importance of non-inferiority trials, most have limited acquaintance with this research design. Educational activities are needed to enhance literacy in non-inferiority trials and the interpretation of non-inferiority margins.
导言:采用非劣效性试验设计评估卒中治疗的新干预措施的情况正在增加。我们设计了一项调查,以评估卒中专家对非劣效性试验和边际的了解和熟悉程度:方法:我们向世界卒中组织(WSO)成员发送了一份简短的网络问卷。根据受访者对非劣效试验的了解程度,总结并报告了受访者提供的不同研究环境下可接受的非劣效边际中位数:共有来自42个国家的120名WSO成员参与了调查。32%的受访者自认为非常熟悉非劣效性试验,6%的受访者认为非常熟悉。当被问及非劣效性试验对改善脑卒中患者护理的影响时,42% 的受访者认为影响很大,45% 的受访者认为影响一般。83%的受访者表示非劣效性试验的结果影响了他们的临床实践。给药的难易程度、标准疗法的相对效果、不适当引入新疗法的临床影响、可用性、价格、储存和运输的难易程度都被认为是影响非劣效性差值大小的因素。随着应答者对非劣效性试验了解的增加,可接受的非劣效性差值的幅度和变异性也在减小:结论:尽管答卷人承认非劣效性试验的重要性,但大多数人对这种研究设计的了解有限。需要开展教育活动,以提高对非劣效试验的认识和对非劣效边际的解释。
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引用次数: 0
Association between apolipoprotein E gene polymorphism and early MR findings in individuals with acute intracerebral hemorrhage: A retrospective cohort analysis 急性脑内出血患者载脂蛋白 E 基因多态性与早期 MR 检查结果之间的关系:一项回顾性队列分析。
IF 2 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-11-10 DOI: 10.1016/j.jstrokecerebrovasdis.2024.108128
Zhenjie Yang M.B. , Qiuxia Xiong M.B. , Rui He M.B. , Chuyue Wu M.D., Ph.D. , Yu Huang M.M. , Qian Li B.N. , Xinghua Liu M.M.

Objective

The Apolipoprotein E (APOE) gene plays a significant role in the development and prognosis of intracerebral hemorrhage (ICH). Imaging features identified within 48 h of ICH onset, particularly on magnetic resonance imaging (MRI), are indicative of cerebral small vessel diseases (CSVD). Our study aimed to assess these imaging characteristics and investigate their association with the APOE gene among ICH patients.

Methods

Clinical and imaging data from patients meeting specific inclusion and exclusion criteria from October 2021 to March 2022 were collected. MR signs or scores were evaluated following international accreditation standards and then analyzed in connection with the APOE allele genes.

Results

In a cohort of 220 patients, ε2 was identified as an independent risk factor for the “multiple subcortical spots” sign (OR = 13.29, 95% CI 1.88-22.59). Furthermore, ε4 emerged as an independent risk factor for the presence of perivascular space (PVS) in the centrum semiovale (OR = 2.46, 95% CI 1.03-5.89) and basal ganglia (OR = 2.64, 95% CI 1.10-6.35), as well as for cerebral microbleeds (CMB) across all locations (OR = 2.38, 95% CI 1.15-6.97), lobar CMB (OR = 2.92, 95% CI 1.11-7.65), and deep CMB (OR = 2.29, 95% CI 1.12-8.67).

Conclusion

The association between APOE ɛ2 and ɛ4 alleles and the presence of “subcortical multiple spots,” “PVS,” and “CMB” indirectly implies the potential role of APOE gene-related pathological changes in the progression of ICH and small vessel pathology.
目的:载脂蛋白 E(APOE)基因在脑内出血(ICH)的发病和预后中起着重要作用。在 ICH 发病 48 小时内发现的影像学特征,尤其是在磁共振成像(MRI)上发现的特征,表明存在脑小血管疾病(CSVD)。我们的研究旨在评估这些成像特征,并调查它们与 ICH 患者 APOE 基因的关系:收集了 2021 年 10 月至 2022 年 3 月期间符合特定纳入和排除标准的患者的临床和影像学数据。按照国际认证标准对 MR 征象或评分进行评估,然后分析其与 APOE 等位基因的关系:结果:在一组 220 例患者中,ε2 被确定为 "多皮层下斑点 "征的独立危险因素(OR = 13.29,95% CI 1.88-22.59)。此外,ε4 是半叶中心(OR = 2.46,95% CI 1.03-5.89)和基底节(OR = 2.64,95% CI 1.10-6.35)出现血管周围间隙(PVS)的独立危险因素。结论:APOE Ⅺ与脑微小出血(CMB)、脑叶CMB(OR = 2.92,95% CI 1.11-7.65)和深部CMB(OR = 2.29,95% CI 1.12-8.67)之间存在关联:APOEɛ2和ɛ4等位基因与 "皮层下多发性斑点"、"PVS "和 "CMB "之间的关联间接暗示了APOE基因相关病理改变在ICH和小血管病变进展中的潜在作用。
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引用次数: 0
Rationale and design of the efficacy and safety of combination of cilostazol and gingko biloba extract EGb 761 in patients with acute non-cardioembolic ischemic stroke (RENEW): A pilot and feasibility randomized controlled trial 西洛他唑和银杏叶提取物 EGb 761 联合治疗急性非心肌栓塞性缺血性脑卒中患者的有效性和安全性(RENEW)的原理与设计:试点和可行性随机对照试验。
IF 2 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-11-10 DOI: 10.1016/j.jstrokecerebrovasdis.2024.108105
Sang Hee Ha MD, PhD , Young Bae Lee MD, PhD , Hyun goo Kang MD, PhD , Kwang-Ho Choi MD, PhD , Beom Joon Kim MD, PhD , Ho Geol Woo MD, PhD , Hyuk Sung Kwon MD, PhD , Tae-Jin Song MD, PhD , Bum Joon Kim MD, PhD

Background

Dual antiplatelet therapy with aspirin and clopidogrel is the standard treatment for acute ischemic stroke (AIS). Cilostazol has emerged as a safe alternative with pleiotropic effects that prevent stroke without increasing the risk of bleeding and has been shown to reduce neurological deterioration (ND) in the acute phase. Ginkgo biloba extract (EGb 761) has also been reported to improve neurological impairment following AIS. This trial aimed to evaluate the efficacy and safety of the combination of cilostazol and EGb 761 in reducing early stroke recurrence and ND in patients with non-cardioembolic AIS.

Methods

The RENEW trial is a prospective, randomized, active-controlled, double-blind, parallel, multicenter phase IV study. Five hundred patients with non-cardioembolic AIS presenting within 72 h of symptom onset will be randomized to receive either aspirin 100 mg and cilostazol 200 mg plus EGb 761 160 mg daily or aspirin 100 mg and clopidogrel 75 mg daily for 90 days. The primary outcomes included the combined ND rate during hospitalization and stroke recurrence within 90 days. Secondary outcomes included the rates of ND, recurrent AIS, hemorrhagic stroke, hemorrhagic transformation, functional outcomes (modified Rankin Scale 0–2), bleeding events, and changes in the dizziness handicap inventory scores.

Discussion

The RENEW trial is expected to provide evidence for the safety and efficacy of combining aspirin, cilostazol, and EGb 761 as an alternative to standard therapy for the acute management of non-cardioembolic AIS.

Trial Registration

This trial was registered at ClinicalTrials.gov (NCT05445895).
背景:阿司匹林和氯吡格雷双重抗血小板疗法是急性缺血性中风(AIS)的标准治疗方法。西洛他唑已成为一种安全的替代疗法,具有多种效应,可在不增加出血风险的情况下预防中风,并已被证明可减少急性期的神经功能恶化(ND)。据报道,银杏叶提取物(EGb 761)也能改善 AIS 后的神经功能损伤。本试验旨在评估西洛他唑和 EGb 761 联合用药在减少非心肌栓塞性 AIS 患者早期卒中复发和 ND 方面的有效性和安全性:RENEW试验是一项前瞻性、随机、主动对照、双盲、平行、多中心IV期研究。500名在症状出现后72小时内就诊的非心肌栓塞性AIS患者将随机接受阿司匹林100毫克、西洛他唑200毫克加EGb 761 160毫克/天,或阿司匹林100毫克、氯吡格雷75毫克/天,为期90天。主要结果包括住院期间的综合 ND 率和 90 天内的中风复发率。次要结果包括ND率、AIS复发率、出血性中风率、出血性转变率、功能结果(改良Rankin量表0-2)、出血事件以及头晕障碍量表评分的变化:RENEW试验有望为阿司匹林、西洛他唑和EGb 761联合治疗非心肌栓塞性AIS的安全性和有效性提供证据:该试验已在 ClinicalTrials.gov (NCT05445895) 上注册。
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引用次数: 0
Investigating the role of gut microbiota in hemorrhagic stroke: Evidence from causal analysis 调查肠道微生物群对出血性中风风险的因果效应:孟德尔随机研究。
IF 2 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-11-09 DOI: 10.1016/j.jstrokecerebrovasdis.2024.108131
Jiaxin Li MD , Chenyang Zang MD , Peihong Li MD , Dandan Sheng MD , Zheng Xiao MD , Bo Xiao MD, PhD , Jian Xia MD , Luo Zhou MD

Background

Hemorrhagic stroke is potentially fatal and debilitating. Previous studies have indicated a potential correlation between gut microbiota and hemorrhagic stroke.

Methods

We conducted a two-sample Mendelian randomization (MR) study to assess the potential causal effects of gut microbiota on hemorrhagic stroke, including nontraumatic intracranial hemorrhage (ntICH), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). The inverse variance weighted (IVW) method was employed as the primary MR evaluation approach. Complementary methods of MR‒Egger, simple mode, weighted mode, and weighted median were utilized for validation. Heterogeneity and pleiotropy were assessed using Cochran's Q and MR‒Egger intercept tests. MR-PRESSO and leave-one-out analyses were employed to identify instrumental outliers.

Results

The IVW estimates demonstrated significant causal associations between ntICH and taxa from two classes (Clostridia, Methanobacteria), one order (Methanobacteriales), two families (Clostridiales vadin BB60 group, Methanobacteriaceae), and two genera (Catenibacterium, unknown genus id. 1000000073) (P<0.05). Subgroup analyses revealed causal links between ICH and taxa from two classes (Clostridia, Methanobacteria), two orders (Methanobacteriales, Rhodospirillales), two families (Acidaminococcaceae, Methanobacteriaceae), and four genera (Butyricimonas, Catenibacterium, Lachnospiraceae UCG010, unknown genus id.2755) (P<0.05). Furthermore, for the SAH subgroup, we identified causal associations with taxa from one family (Rikenellaceae) and six genera (Alloprevotella, Enterorhabdus, Hungatella, Lachnoclostridium, Parabacteroides, Ruminococcus gauvreauii group) (P<0.05). These findings remained robust across all sensitivity tests.

Conclusions

Our findings provide support for the causal effects of specific gut microbial taxa on hemorrhagic stroke and identify promising targets for its prevention and therapy. Further research is warranted to validate these associations.
背景:出血性脑卒中可能致命并使人衰弱。以前的研究表明,肠道微生物群与出血性中风之间存在潜在的相关性:我们进行了一项双样本孟德尔随机化(MR)研究,以评估肠道微生物群对出血性中风(包括非创伤性颅内出血(ntICH)、脑内出血(ICH)和蛛网膜下腔出血(SAH))的潜在因果效应。反方差加权(IVW)法被用作主要的磁共振评估方法。此外,还采用了 MR-Egger、简单模式、加权模式和加权中值等补充方法。使用 Cochran's Q 和 MR-Egger 截距检验评估了异质性和多义性。采用MR-PRESSO和leave-one-out分析来识别工具异常值:结果:IVW 估计值表明,ntICH 风险与两个类(梭菌属、甲烷杆菌)、一个目(甲烷杆菌科)、两个科(梭菌属 vadin BB60 组、甲烷杆菌科)和两个属(卡氏菌属、未知属 id.1000000073)的类群之间存在显著关联(结论:我们的研究结果为 ntICH 的因果关系提供了支持:我们的研究结果为特定肠道微生物类群对出血性中风的因果效应提供了支持,并为其预防和治疗确定了有前景的靶点。还需要进一步研究来验证这些关联。
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引用次数: 0
To bridge or not to bridge: The role of intravenous thrombolysis in mechanical thrombectomy for large cerebral infarctions through a two-center cohort study and meta-analysis 桥接还是不桥接:通过双中心队列研究和荟萃分析探讨静脉溶栓在大面积脑梗塞机械取栓术中的作用。
IF 2 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-11-09 DOI: 10.1016/j.jstrokecerebrovasdis.2024.108115
Wang Chen MD , Lei Yang MD , Simeng Wang MD , Ji Liu MD , Mengen Wang MD , Jincheng Wu MD , Wei Qin MD , Xianjun Wang MD , Wenli Hu MD

Background

The effectiveness and safety of intravenous thrombolysis before mechanical thrombectomy (MT) in large cerebral infarctions remains uncertain. This study compares bridging MT, which includes intravenous thrombolysis, to direct MT without it.

Methods

Data from 298 patients with anterior circulation large cerebral infarctions, assessed via non-enhanced CT (ASPECTS 0-5), who underwent MT in two-center cohort studies, were analyzed. Primary outcomes focused on independent ambulation (modified Rankin Scale scores 0-3) at 90 days post-stroke. Safety outcomes included parenchymal hemorrhage (PH) rates and mortality. We conducted a sensitivity analysis considering the timing from symptom onset to imaging within 4.5 hours. Additionally, a meta-analysis of 17 studies involving 3527 patients assessed the interventions' effectiveness and safety, with further scrutiny of high-quality studies (Newcastle-Ottawa Scale ratings 7-9) to increase robustness of results.

Results

No significant differences were found in 90-day independent ambulation between the bridging MT and the direct MT group (adjusted odds ratio [aOR] 1.15, 95% CI 0.68-1.94). Rates of PH and mortality were also similar across groups. These outcomes were consistent in the subgroup imaged within 4.5 hours of symptom onset. The meta-analysis supported these outcomes, showing no improvement in ambulation (aOR 1.16, 95% CI 0.82-1.64) or reduction in PH with bridging MT. Further analysis of high-quality studies supported these results.

Conclusions

The cohort study and meta-analysis provide Class II evidence indicating no significant differences in functional outcomes or hemorrhagic risks between bridging and direct MT for large cerebral infarctions. This suggests that direct MT might be a viable alternative to bridging MT.
背景:在大面积脑梗死的机械取栓术(MT)之前进行静脉溶栓的有效性和安全性仍不确定。本研究比较了包括静脉溶栓的桥接式机械取栓术和不包括静脉溶栓的直接机械取栓术:方法:分析了298名前循环大面积脑梗塞患者的数据,这些患者通过非增强CT(ASPECTS 0-5)进行评估,并在两个中心的队列研究中接受了MT。主要结果集中在中风后90天的独立行走能力(修改后的Rankin量表评分0-3)。安全性结果包括实质出血(PH)率和死亡率。我们进行了一项敏感性分析,考虑到从症状发作到成像的时间应在 4.5 小时内。此外,我们还对涉及 3527 名患者的 17 项研究进行了荟萃分析,评估了干预措施的有效性和安全性,并对高质量研究(纽卡斯尔-渥太华量表评分 7-9 级)进行了进一步审查,以提高结果的稳健性:桥接 MT 组和直接 MT 组在 90 天独立行走方面无明显差异(调整赔率比 [aOR] 1.15,95% CI 0.68-1.94)。各组的 PH 和死亡率也相似。在症状出现后 4.5 小时内成像的亚组中,这些结果是一致的。荟萃分析支持这些结果,显示桥接 MT 未改善行走能力(aOR 1.16,95% CI 0.82-1.64)或降低 PH。对高质量研究的进一步分析也支持这些结果:队列研究和荟萃分析提供了II级证据,表明桥接式MT和直接MT治疗大面积脑梗死在功能预后或出血风险方面没有显著差异。这表明直接MT可能是桥接MT的可行替代方案。
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引用次数: 0
Associations between chinese visceral adiposity index and incident stroke among community populations in Pudong New Area, Shanghai 上海市浦东新区社区居民的中国人内脏脂肪指数与脑卒中发病率之间的关系。
IF 2 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-11-08 DOI: 10.1016/j.jstrokecerebrovasdis.2024.108100
Qingping Liu, Yi Zhou, Kang Wu, Jiahui Song, Juzhong Ke, Hua Qiu, Zhitao Li, Xiaonan Ruan

Background

To analyze the relationship between Chinese Visceral Adiposity Index (CVAI) and stroke in Pudong New Area, and to provide a scientific basis for the prevention and treatment of this condition.

Materials and Methods

Based on the Follow-up Cohort Program of Chronic Disease Risk Factors in Pudong New Area, a total of 7,194 residents from 12 townships and 35 village committees or neighborhood committees were selected. The cohort data in 2016 served as the baseline, and a follow-up was conducted on 5462 individuals from 2019 to 2020.

Results

In the analysis of stroke incidence, 5,462 subjects were included, with 616 stroke events recorded. The incidence density of stroke was 33.41 per 1000 person-years, while the China standard rate and the world standard rate were 13.78 and 12.52 per 1000 person-years, respectively. The incidence density of stroke rose with increasing quartiles of CVAI. After adjusting for potential confounders, the risk of stroke for males and females with CVAI ≥ 132.11 was 2.492 times (95% CI: 1.457 ∼ 4.260) and 1.759 times (95% CI: 1.070-2.891), respectively, compared to the groups with CVAI < 81.91. Among the eight obesity indicators, including CVAI, Visceral Adiposity Index (VAI), Body Mass Index (BMI), Waist Circumference (WC), Waist Hip Ratio (WHR), Waist Height Ratio (WHtR), Body Adiposity Index (BAI), A Body Shape Index (ABSI),and Body Roundness Index (BRI), CVAI has the highest diagnostic accuracy for female stroke using Receiver Operator Characteristic (ROC) curves (the Area under the ROC curve/AUC = 0.619). Subgroup analysis showed that smoking and dyslipidemia significantly modified the association between CVAI and stroke risk in females (interaction P < 0.05).

Conclusions

CVAI is identified as a significant risk factor for stroke and serves as a valuable predictor of stroke, particularly in females.
背景:分析浦东新区中国人内脏脂肪指数(CVAI)与脑卒中的关系,为该病的预防和治疗提供科学依据:分析浦东新区中国人内脏脂肪指数(CVAI)与脑卒中的关系,为脑卒中的防治提供科学依据:基于 "浦东新区慢性病危险因素队列随访项目",选取浦东新区12个乡镇、35个村委会或居委会共7194名居民作为研究对象。以2016年的队列数据为基线,2019年至2020年对5462人进行了随访:在脑卒中发病率分析中,共纳入 5462 名受试者,记录了 616 起脑卒中事件。脑卒中的发病密度为每千人年 33.41 例,而中国标准发病率和世界标准发病率分别为每千人年 13.78 例和 12.52 例。脑卒中的发病密度随着 CVAI 四分位数的增加而上升。在调整了潜在的混杂因素后,CVAI≥132.11 的男性和女性与 CVAI<81.91 的人群相比,脑卒中风险分别为 2.492 倍(95% CI:1.457 ∼ 4.260)和 1.759 倍(95% CI:1.070 ∼ 2.891)。在八项肥胖指标中,包括 CVAI、内脏脂肪指数 (VAI)、体重指数 (BMI)、腰围 (WC)、腰臀比 (WHR)、腰高比 (WHTR)、身体脂肪指数 (BAI)、根据接收者特征曲线(ROC),CVAI 对女性中风的诊断准确率最高(ROC 曲线下面积/AUC = 0.619)。619).亚组分析显示,吸烟和血脂异常会显著改变女性 CVAI 与中风风险之间的关联(交互作用 P < 0.05):结论:CVAI 是脑卒中的重要危险因素,是预测脑卒中的重要指标,尤其是对女性而言。
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引用次数: 0
Hydroxysafflor Yellow A promotes angiogenesis of brain microvascular endothelial cells from ischemia/reperfusion injury via glycolysis pathway in vitro 羟基红花黄色素 A 在体外通过糖酵解途径促进缺血再灌注损伤的脑微血管内皮细胞的血管生成。
IF 2 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-11-07 DOI: 10.1016/j.jstrokecerebrovasdis.2024.108107
Juxuan Ruan , Lei Wang , Ning Wang , Ping Huang , Dennis Chang , Xian Zhou , Saiwang Seto , Dan Li , Jincai Hou

Background

Angiogenesis of brain microvascular endothelial cells (BMECs) after cerebral ischemia was conducive to improving the blood supply of ischemia tissues, which was upregulated by glycolysis. Hydroxysafflor Yellow A (HSYA) mends damaged tissues through increasing angiogenesis.

Methods

HSYA treated proliferation, migration and angiogenesis of BMECs in vitro in vitro during OGD/R. HSYA regulated the key enzymes of glycolysis, such as hexokinase 2 (HK2) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), glucose uptake and products (pyruvate, ATP and lactate) were detected by western blot and kits, respectively. Scratch wound assay, transwell, tube formation and spheroid sprouting were used to explore the pathway that HSYA recovered migration and angiogenesis of BMECs. We evaluated the potential target of HSYA promoting glycolysis via molecular docking, drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA).

Results

HSYA promoted the proliferation, migration, tube formation and spheroid sprouting of BMECs during OGD/R, and stimulated the expression of tip phenotype marker protein (CD34), and the receptor (Notch-1) that regulated the differentiation of endothelial cells into tip/stalk phenotype. In glycolysis, PFKFB3 expression was upregulated by HSYA; HSYA also improved ATP and pyruvate levels, as well as lactate release after OGD/R. Finally, upregulating VEGFA and p-VEGFR2 of HSYA was weakened because of suppressing glycolysis; the HSYA's improvement of BMECs migration and angiogenesis was attenuated under the inhibition of glycolysis, which confirmed that HSYA were upregulating angiogenesis and expression of VEGFA/VEGFR2 by glycolysis pathway. The result about molecular docking, DARTS and CETSA suggested that PFKFB3 was the possible target of HSYA.

Conclusion

HSYA promotes angiogenesis of BMECs in vitro through the glycolysis mediated VEGFA/VEGFR2 pathway, and PFKFB3 is the potential target of HSYA to heighten glycolysis.
背景:脑缺血后脑微血管内皮细胞(BMECs)的血管生成有利于改善缺血组织的血液供应,而糖酵解会上调血管生成。方法:Hydroxysafflor Yellow A(HSYA)通过增加血管生成来修复受损组织。HSYA调节糖酵解的关键酶,如己糖激酶2(HK2)和6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶3(PFKFB3),葡萄糖摄取和产物(丙酮酸、ATP和乳酸)分别通过Western印迹和试剂盒检测。采用划痕法、Transwell法、管形成法和球形萌发法探讨了HSYA恢复BMECs迁移和血管生成的途径。我们通过分子对接、药物亲和力反应靶点稳定性(DARTS)和细胞热转移试验(CETSA)评估了HSYA促进糖酵解的潜在靶点:结果:HSYA在OGD/R过程中促进了BMECs的增殖、迁移、管形成和球形萌发,并刺激了尖端表型标志蛋白(CD34)和受体(Notch-1)的表达,从而调控内皮细胞向尖端/茎表型分化。在糖酵解方面,HSYA 上调了 PFKFB3 的表达;HSYA 还改善了 ATP 和丙酮酸的水平,以及 OGD/R 后乳酸的释放。最后,HSYA对VEGFA和p-VEGFR2的上调作用因抑制糖酵解而减弱;在抑制糖酵解的条件下,HSYA对BMECs迁移和血管生成的改善作用减弱,证实HSYA通过糖酵解途径上调血管生成和VEGFA/VEGFR2的表达。分子对接、DARTS和CETSA结果表明,PFKFB3可能是HSYA的靶点:结论:HSYA 通过糖酵解介导的 VEGFA/VEGFR2 通路促进体外 BMECs 的血管生成,而 PFKFB3 是 HSYA 促进糖酵解的潜在靶点。
{"title":"Hydroxysafflor Yellow A promotes angiogenesis of brain microvascular endothelial cells from ischemia/reperfusion injury via glycolysis pathway in vitro","authors":"Juxuan Ruan ,&nbsp;Lei Wang ,&nbsp;Ning Wang ,&nbsp;Ping Huang ,&nbsp;Dennis Chang ,&nbsp;Xian Zhou ,&nbsp;Saiwang Seto ,&nbsp;Dan Li ,&nbsp;Jincai Hou","doi":"10.1016/j.jstrokecerebrovasdis.2024.108107","DOIUrl":"10.1016/j.jstrokecerebrovasdis.2024.108107","url":null,"abstract":"<div><h3>Background</h3><div>Angiogenesis of brain microvascular endothelial cells (BMECs) after cerebral ischemia was conducive to improving the blood supply of ischemia tissues, which was upregulated by glycolysis. Hydroxysafflor Yellow A (HSYA) mends damaged tissues through increasing angiogenesis.</div></div><div><h3>Methods</h3><div>HSYA treated proliferation, migration and angiogenesis of BMECs in vitro <em>in vitro</em> during OGD/R. HSYA regulated the key enzymes of glycolysis, such as hexokinase 2 (HK2) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), glucose uptake and products (pyruvate, ATP and lactate) were detected by western blot and kits, respectively. Scratch wound assay, transwell, tube formation and spheroid sprouting were used to explore the pathway that HSYA recovered migration and angiogenesis of BMECs. We evaluated the potential target of HSYA promoting glycolysis via molecular docking, drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA).</div></div><div><h3>Results</h3><div>HSYA promoted the proliferation, migration, tube formation and spheroid sprouting of BMECs during OGD/R, and stimulated the expression of tip phenotype marker protein (CD34), and the receptor (Notch-1) that regulated the differentiation of endothelial cells into tip/stalk phenotype. In glycolysis, PFKFB3 expression was upregulated by HSYA; HSYA also improved ATP and pyruvate levels, as well as lactate release after OGD/R. Finally, upregulating VEGFA and p-VEGFR2 of HSYA was weakened because of suppressing glycolysis; the HSYA's improvement of BMECs migration and angiogenesis was attenuated under the inhibition of glycolysis, which confirmed that HSYA were upregulating angiogenesis and expression of VEGFA/VEGFR2 by glycolysis pathway. The result about molecular docking, DARTS and CETSA suggested that PFKFB3 was the possible target of HSYA.</div></div><div><h3>Conclusion</h3><div>HSYA promotes angiogenesis of BMECs <em>in vitro</em> through the glycolysis mediated VEGFA/VEGFR2 pathway, and PFKFB3 is the potential target of HSYA to heighten glycolysis.</div></div>","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"34 1","pages":"Article 108107"},"PeriodicalIF":2.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Causal association between COVID-19 vaccination and thrombosis-related biomarkers/thrombosis/ischemic stroke: Mendelian randomization study COVID-19疫苗接种与血栓相关生物标志物/血栓形成/缺血性中风之间的因果关系:孟德尔随机化研究。
IF 2 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-11-07 DOI: 10.1016/j.jstrokecerebrovasdis.2024.108113
Xiaoqi Peng , Lianjia Zhuo , Yong Ma , Yingxia Liu , Zeming Wu

Background

Observational studies about the association between coronavirus disease 2019 (COVID-19) vaccination and thrombosis/ischemic stroke are inconsistent. The aim of this study is to assess the causality between COVID-19 vaccination and thrombosis-related biomarkers/thrombosis/ischemic stroke using mendelian randomization (MR) analysis.

Methods

A two-sample MR analysis using publicly available genome-wide association study (GWAS) data was conducted. Causal effects were appraised using inverse variance weighted (IVW, as a primary method), with supplementary methods including constrained maximum likelihood and model averaging, MR-Robust Adjusted Profile Score, MR-Egger regression, simple mode, weighted median, and weighted mode. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis.

Results

Genetically predicted COVID-19 vaccination was negatively associated with C-C motif chemokine 3 [CCL3, odds ratio (OR): 0.694, 95% confidence intervals (CI): 0.484-0.995] and multiple coagulation factor deficiency protein 2 (MCFD2, OR: 0.806, 95% CI: 0.675-0.963). Meanwhile, the IVW analysis revealed significant causal effects between genetically predicted COVID-19 vaccination and ischemic stroke (OR: 1.088, 95% CI: 1.006-1.177), large artery stroke (LAS, OR: 1.251, 95% CI: 1.028-1.521). The leave-one-out analysis revealed that no individual SNP exerted a significant effect on the overall causal estimate.

Conclusion

Our study provided evidence supporting a potential causal association of genetically predicted COVID-19 vaccination with CCL3 levels, MCFD2 levels, ischemic stroke risk and LAS risk. These results provide preliminary evidence of potential adverse associations, but further studies are required to fully understand the mechanisms and to validate these findings across broader populations.
背景:有关接种冠状病毒病2019(COVID-19)疫苗与血栓形成/缺血性中风之间关系的观察性研究结果并不一致。本研究的目的是利用亡羊补牢随机化(MR)分析法评估接种COVID-19疫苗与血栓相关生物标志物/血栓形成/缺血性中风之间的因果关系:利用公开的全基因组关联研究(GWAS)数据进行了双样本 MR 分析。因果效应的评估采用反方差加权法(IVW,作为主要方法),辅助方法包括约束最大似然法和模型平均法、MR-Robust Adjusted Profile Score、MR-Egger 回归、简单模式、加权中位数和加权模式。使用 Cochran's Q 检验、MR-Egger 截距检验和遗漏分析进行了敏感性分析:结果:基因预测的 COVID-19 疫苗接种与 C-C motif 趋化因子 3 [CCL3,比值比 (OR):0.694,95% 置信区间 (CI):0.484-0.995] 和多凝血因子缺乏蛋白 2 (MCFD2,OR:0.806,95% CI:0.675-0.963) 呈负相关。同时,IVW分析显示,基因预测的COVID-19疫苗接种与缺血性中风(OR:1.088,95% CI:1.006-1.177)、大动脉中风(LAS,OR:1.251,95% CI:1.028-1.521)之间存在显著的因果效应。撇除分析显示,没有单个 SNP 对总体因果关系估计值产生显著影响:我们的研究提供了证据,支持基因预测的 COVID-19 疫苗接种与 CCL3 水平、MCFD2 水平、缺血性中风风险和 LAS 风险之间存在潜在的因果关系。这些结果提供了潜在不良关联的初步证据,但还需要进一步的研究来充分了解其机制,并在更广泛的人群中验证这些发现。
{"title":"Causal association between COVID-19 vaccination and thrombosis-related biomarkers/thrombosis/ischemic stroke: Mendelian randomization study","authors":"Xiaoqi Peng ,&nbsp;Lianjia Zhuo ,&nbsp;Yong Ma ,&nbsp;Yingxia Liu ,&nbsp;Zeming Wu","doi":"10.1016/j.jstrokecerebrovasdis.2024.108113","DOIUrl":"10.1016/j.jstrokecerebrovasdis.2024.108113","url":null,"abstract":"<div><h3>Background</h3><div>Observational studies about the association between coronavirus disease 2019 (COVID-19) vaccination and thrombosis/ischemic stroke are inconsistent. The aim of this study is to assess the causality between COVID-19 vaccination and thrombosis-related biomarkers/thrombosis/ischemic stroke using mendelian randomization (MR) analysis.</div></div><div><h3>Methods</h3><div>A two-sample MR analysis using publicly available genome-wide association study (GWAS) data was conducted. Causal effects were appraised using inverse variance weighted (IVW, as a primary method), with supplementary methods including constrained maximum likelihood and model averaging, MR-Robust Adjusted Profile Score, MR-Egger regression, simple mode, weighted median, and weighted mode. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis.</div></div><div><h3>Results</h3><div>Genetically predicted COVID-19 vaccination was negatively associated with C-C motif chemokine 3 [CCL3, odds ratio (OR): 0.694, 95% confidence intervals (CI): 0.484-0.995] and multiple coagulation factor deficiency protein 2 (MCFD2, OR: 0.806, 95% CI: 0.675-0.963). Meanwhile, the IVW analysis revealed significant causal effects between genetically predicted COVID-19 vaccination and ischemic stroke (OR: 1.088, 95% CI: 1.006-1.177), large artery stroke (LAS, OR: 1.251, 95% CI: 1.028-1.521). The leave-one-out analysis revealed that no individual SNP exerted a significant effect on the overall causal estimate.</div></div><div><h3>Conclusion</h3><div>Our study provided evidence supporting a potential causal association of genetically predicted COVID-19 vaccination with CCL3 levels, MCFD2 levels, ischemic stroke risk and LAS risk. These results provide preliminary evidence of potential adverse associations, but further studies are required to fully understand the mechanisms and to validate these findings across broader populations.</div></div>","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"34 1","pages":"Article 108113"},"PeriodicalIF":2.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy of anodal transcranial direct current stimulation for upper extremity function after ischemic stroke: A systematic review of parallel randomized clinical trials 阳极经颅直流电刺激对缺血性中风后上肢功能的疗效:平行随机临床试验的系统回顾》。
IF 2 4区 医学 Q3 NEUROSCIENCES Pub Date : 2024-11-04 DOI: 10.1016/j.jstrokecerebrovasdis.2024.108112
Liqiang Yu RN, MS (Nurse) , Han Chen MD, PhD (Associate Chief Physician) , Chaiying Chen RN, BS (Charge Nurse) , Yang Lin RN, BS (Associate Chief Nurse) , Zhuofan Huang RN, BS (Charge Nurse) , Jianhong Wang RN, MS (Associate Chief Nurse) , Qiaoling Chen RN, MS (Chief Nurse)

Background

Although existing studies had shown therapeutic effects of transcranial direct current stimulation (tDCS) on upper limb dysfunction after stroke, previous systematic reviews had mostly provided general analyses on the polarity of tDCS and the type of stroke, with inconsistent results. We aimed to determine the efficacy of anodal transcranial direct current stimulation in enhancing upper extremity function following ischemic stroke.

Methods

A comprehensive search was conducted across a variety of databases, spanning from their inception to March 15th, 2024.The focus was on parallel randomized clinical trials published that explored the impact of anodal transcranial direct current stimulation on upper extremity function in ischemic stroke patients. Data extraction and quality assessment were conducted independently by two reviewers. The Cochrane Risk of Bias Tool was utilized to assess the risk of bias in the included studies.

Results

A total of 19 studies involving 1032 participants were included in the analysis. The pooled results of these studies indicated that anodal transcranial direct current stimulation had a positive impact on the Fugl-Meyer Assessment Upper Extremity, Wolf Motor Function Test, Resting Motion Threshold, and Barthel Index Score in ischemic stroke patients with upper extremity dysfunction. Follow-up data suggested the potential long-term efficacy of anodal transcranial direct current stimulation in ischemic stroke. Reported adverse reactions indicated that anodal transcranial direct current stimulation was relatively safe for stroke patients.

Conclusions

Anodal transcranial direct current stimulation is an effective intervention and relatively safe and effective intervention for improving upper extremity function in ischemic stroke patients.
背景:尽管现有研究显示经颅直流电刺激(tDCS)对中风后上肢功能障碍有治疗作用,但之前的系统性综述大多对tDCS的极性和中风类型进行了一般性分析,结果并不一致。我们旨在确定阳极经颅直流电刺激对缺血性中风后增强上肢功能的疗效:我们在各种数据库中进行了全面搜索,搜索时间跨度从数据库建立之初到 2024 年 3 月 15 日,重点是已发表的探讨阳极经颅直流电刺激对缺血性中风患者上肢功能影响的平行随机临床试验。数据提取和质量评估由两名审稿人独立完成。利用 Cochrane 偏倚风险工具评估纳入研究的偏倚风险:共有 19 项研究纳入分析,涉及 1032 名参与者。这些研究的汇总结果表明,阳极经颅直流电刺激对有上肢功能障碍的缺血性中风患者的 Fugl-Meyer 上肢评估、Wolf 运动功能测试、静息运动阈值和 Barthel 指数评分有积极影响。随访数据表明,阳极经颅直流电刺激对缺血性中风具有潜在的长期疗效。报告的不良反应表明,阳极经颅直流电刺激对中风患者相对安全:结论:阳极经颅直流电刺激是改善缺血性中风患者上肢功能的有效干预措施,而且相对安全有效。
{"title":"Efficacy of anodal transcranial direct current stimulation for upper extremity function after ischemic stroke: A systematic review of parallel randomized clinical trials","authors":"Liqiang Yu RN, MS (Nurse) ,&nbsp;Han Chen MD, PhD (Associate Chief Physician) ,&nbsp;Chaiying Chen RN, BS (Charge Nurse) ,&nbsp;Yang Lin RN, BS (Associate Chief Nurse) ,&nbsp;Zhuofan Huang RN, BS (Charge Nurse) ,&nbsp;Jianhong Wang RN, MS (Associate Chief Nurse) ,&nbsp;Qiaoling Chen RN, MS (Chief Nurse)","doi":"10.1016/j.jstrokecerebrovasdis.2024.108112","DOIUrl":"10.1016/j.jstrokecerebrovasdis.2024.108112","url":null,"abstract":"<div><h3>Background</h3><div>Although existing studies had shown therapeutic effects of transcranial direct current stimulation (tDCS) on upper limb dysfunction after stroke, previous systematic reviews had mostly provided general analyses on the polarity of tDCS and the type of stroke, with inconsistent results. We aimed to determine the efficacy of anodal transcranial direct current stimulation in enhancing upper extremity function following ischemic stroke.</div></div><div><h3>Methods</h3><div>A comprehensive search was conducted across a variety of databases, spanning from their inception to March 15th, 2024.The focus was on parallel randomized clinical trials published that explored the impact of anodal transcranial direct current stimulation on upper extremity function in ischemic stroke patients. Data extraction and quality assessment were conducted independently by two reviewers. The Cochrane Risk of Bias Tool was utilized to assess the risk of bias in the included studies.</div></div><div><h3>Results</h3><div>A total of 19 studies involving 1032 participants were included in the analysis. The pooled results of these studies indicated that anodal transcranial direct current stimulation had a positive impact on the Fugl-Meyer Assessment Upper Extremity, Wolf Motor Function Test, Resting Motion Threshold, and Barthel Index Score in ischemic stroke patients with upper extremity dysfunction. Follow-up data suggested the potential long-term efficacy of anodal transcranial direct current stimulation in ischemic stroke. Reported adverse reactions indicated that anodal transcranial direct current stimulation was relatively safe for stroke patients.</div></div><div><h3>Conclusions</h3><div>Anodal transcranial direct current stimulation is an effective intervention and relatively safe and effective intervention for improving upper extremity function in ischemic stroke patients.</div></div>","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"34 1","pages":"Article 108112"},"PeriodicalIF":2.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Stroke & Cerebrovascular Diseases
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