Immunothrombosis in Acute Ischemic Stroke

Stroke, Ahead of Print. Ischemic stroke is one of the leading causes of disability and mortality worldwide. Thrombosis is the main pathological process of stroke and is therefore an important therapeutic target in stroke prevention. In recent years, with the development of endovascular treatment and therefore retrieving the thrombus for further investigation, evidence is accumulating that immune cells are inextricably linked to stroke pathogenesis. Circulating immune cells have been found to induce immunothrombosis, and they actively participate in the formation of the thrombus by promoting platelet recruitment and thrombin activation. Additionally, the formation of thromboinflammation leads to increased instability of atherosclerotic plaques. We review the concepts of stroke immunothrombosis and thromboinflammation and the effect of immune cells on vessel recanalization and patient outcome. In addition, we elaborate on the possible mechanism of immune cells being activated and participating in thrombosis in ischemic stroke.

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Ottobre 2024

Plasma Phenylacetylglutamine Levels and Prognosis of Ischemic Stroke: A Multicenter Prospective Study Based on the CATIS Trial

Stroke, Volume 55, Issue 11, Page 2652-2660, November 1, 2024. BACKGROUND:Phenylacetylglutamine is implicated in platelet clotting and thrombosis, but its prognostic value in ischemic stroke remains unclear. We aimed to explore the associations of plasma phenylacetylglutamine levels with adverse outcomes after ischemic stroke in a multicenter prognostic cohort study.METHODS:Our multicenter prognostic cohort study included 3564 Chinese patients with ischemic stroke from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). All patients were followed up at 3 months after ischemic stroke onset. The primary outcome was the composite outcome of death or major disability (modified Rankin Scale score, 3–6) at 3 months after ischemic stroke.RESULTS:During 3 months of follow-up, 877 participants experienced the primary outcome. After multivariate adjustment, each 500 ng/mL increase of phenylacetylglutamine was associated with a 7% (P=0.012), 6% (P=0.016), and 6% (P=0.028) increased risk of the primary outcome, major disability, and death, respectively. The odds ratios or hazard ratios in the highest versus the lowest quartile of plasma phenylacetylglutamine were 1.62 ([95% CI, 1.18–2.23];Ptrend=0.001) for the primary outcome, 1.62 ([95% CI, 1.16–2.24];Ptrend=0.001) for major disability, and 2.59 ([95% CI, 1.19–5.60];Ptrend=0.025) for death, respectively. There was a significantly worse shift in the distribution of modified Rankin Scale score at 3 months with higher phenylacetylglutamine quartiles (Ptrend=0.003). Multiple-adjusted spline regression model showed a linear relationship between phenylacetylglutamine and primary outcome (Pvalue for linearity

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Ottobre 2024

Long-Term Neurologic Outcomes in Pediatric Arterial Ischemic Stroke: The Impact of Age and Lesion Location

Stroke, Volume 55, Issue 11, Page 2622-2631, November 1, 2024. BACKGROUND:The impact of age-at-stroke on outcome following pediatric arterial ischemic stroke remains controversial. We studied the interaction of age-at-stroke and infarct location and extent with long-term neurological outcomes.METHODS:We conducted a longitudinal prospective outcome study of children with acute pediatric arterial ischemic stroke diagnosed from 1996 to 2016 at the Hospital for Sick Children, Toronto, Canada. Pediatric Stroke Outcome Measure scores were dichotomized as normal or abnormal (ie, mild, moderate, or severe). Outcomes were analyzed by age-at-stroke (newborn: birth to 28 days; early childhood: 29 days to 5 years; middle/late childhood: >5–18 years), and infarct location, based on each of the following: model 1: circulation (anterior/posterior); model 2: cortical versus subcortical involvement; and model 3: specific arterial territory, including infarct extent (small [

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Ottobre 2024

An Introduction to Bayesian Approaches to Trial Design and Statistics for Stroke Researchers

Stroke, Ahead of Print. While the majority of stroke researchers use frequentist statistics to analyze and present their data, Bayesian statistics are becoming more and more prevalent in stroke research. As opposed to frequentist approaches, which are based on the probability that data equal specific values given underlying unknown parameters, Bayesian approaches are based on the probability that parameters equal specific values given observed data and prior beliefs. The Bayesian paradigm allows researchers to update their beliefs with observed data to provide probabilistic interpretations of key parameters, for example, the probability that a treatment is effective. In this review, we outline the basic concepts of Bayesian statistics as they apply to stroke trials, compare them to the frequentist approach using exemplary data from a randomized trial, and explain how a Bayesian analysis is conducted and interpreted.

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Ottobre 2024

Changing Landscape of Randomized Clinical Trials in Stroke: Explaining Contemporary Trial Designs and Methods

Stroke, Ahead of Print. Evidence generated from randomized clinical trials (RCTs) plays an indispensable role in advancing clinical stroke care. Although the number of stroke-related RCTs published every year has grown exponentially over the past 25 years, the execution and completion of RCTs, particularly those conducted in a hyperacute setting, have grown more complicated and challenging over the years. In addition to the practical challenges associated with conducting a clinical trial, like obtaining human subjects approval, identifying clinical sites, training trial personnel, and enrolling the target number of patients within the available funding and timeline, the complexity of contemporary RCT designs and analyses has become much more exacting. It is no longer sufficient to have a decent understanding of the 2-arm, placebo-controlled RCT, combined with a rudimentary grasp of thePvalue; things are now much more complicated. Innovations in trial design and analysis, including adaptive, Bayesian, platform, and noninferiority designs, have occurred to address the problems of poor trial efficiency. However, these advances require the end user to have a much greater level of understanding regarding the rationale, conduct, analysis, and interpretation of each design. While these newer designs seek greater efficiency, there are inevitably tradeoffs that need to be understood. In this month’s edition ofStroke, we introduce a new series designed to help fill in these knowledge gaps. Over the next few months, 4 papers will be published that address major design innovations (adaptive, Bayesian, platform, and noninferiority) with the aim of illustrating how these approaches can make trials more efficient (where efficiency is defined as getting to the right answer, sooner, with a potentially lower sample size). In addition to introducing this series, this current article also reviews traditional hypothesis testing and the common misinterpretations of thePvalue; fortunately, new philosophical schools of inference are beginning to vanquish the overreliance on thePvalue. We are excited about the opportunity to educate theStrokereadership about these new trial designs and the profound implications that they bring.

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Ottobre 2024

Adaptive Clinical Trials in Stroke

Stroke, Ahead of Print. Designing a clinical trial to evaluate the efficacy of an intervention is often complicated by uncertainty over aspects of the study population, potential treatment effects, most relevant outcomes, dropouts, and other factors. However, once participants begin to be enrolled and partial trial data become available, this level of uncertainty is reduced. Adaptive clinical trials are designed to take advantage of the accumulating data during the conduct of a trial to make changes according to prespecified decision rules to increase the likelihood of success or statistical efficiency. Common adaptive rules address early stopping for benefit or futility, sample size reestimation, adding or dropping treatment arms or altering randomization ratios, and changing the eligibility criteria to focus on responder patient subgroups. Adaptive clinical trials are gaining popularity for clinical stroke research. We provide an overview of the methods, practical considerations, challenges and limitations, and potential future role of adaptive clinical trials in advancing knowledge and practice in stroke.

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Ottobre 2024

CT-Guided Thrombectomy for Large Core Stroke Up to 24 Hours

Prevailing dogma in the treatment of acute ischemic stroke has long dictated that endovascular reperfusion of large infarcted areas distal to an occluded large intracranial artery is detrimental to patient outcomes. These concerns were rooted in the presumed deleterious effects of reperfusion, most notably symptomatic intracranial hemorrhage, and in the constrained opportunity to improve outcome due to the substantial infarction already present. Indeed, the initial waves of positive randomized endovascular stroke trials addressing thrombectomy in the early time window (0-6 hours) and with imaging selection in the late time window (6-24 hours) generally excluded from enrollment patients with a large baseline infarct (core). However, among the relatively small number of patients with large core infarcts inadvertently enrolled in these trials, analyses suggested an acceptable safety profile and potential benefit of thrombectomy. These rather unexpected findings led to the launch of several randomized trials prospectively assessing the efficacy and safety of thrombectomy in patients with acute ischemic stroke presenting with a large core and proximal large vessel occlusion in the anterior circulation. Across these trials, characterization of the infarcted brain has occurred with different imaging modalities using different definitions for what constitutes a large core, but common to all trials has been a requirement that infarction already be present on computed tomography (CT) or magnetic resonance imaging (MRI) in at least 5 of the 10 regions of the Alberta Stroke Program Early CT Score (ASPECTS) scale.

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Ottobre 2024

2024 Guideline for the Primary Prevention of Stroke: A Guideline From the American Heart Association/American Stroke Association

Stroke, Ahead of Print. AIM:The “2024 Guideline for the Primary Prevention of Stroke” replaces the 2014 “Guidelines for the Primary Prevention of Stroke.” This updated guideline is intended to be a resource for clinicians to use to guide various prevention strategies for individuals with no history of stroke.METHODS:A comprehensive search for literature published since the 2014 guideline; derived from research involving human participants published in English; and indexed in MEDLINE, PubMed, Cochrane Library, and other selected and relevant databases was conducted between May and November 2023. Other documents on related subject matter previously published by the American Heart Association were also reviewed.STRUCTURE:Ischemic and hemorrhagic strokes lead to significant disability but, most important, are preventable. The 2024 primary prevention of stroke guideline provides recommendations based on current evidence for strategies to prevent stroke throughout the life span. These recommendations align with the American Heart Association’s Life’s Essential 8 for optimizing cardiovascular and brain health, in addition to preventing incident stroke. We also have added sex-specific recommendations for screening and prevention of stroke, which are new compared with the 2014 guideline. Many recommendations for similar risk factor prevention were updated, new topics were reviewed, and recommendations were created when supported by sufficient-quality published data.

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Ottobre 2024

Twenty Years of Sustained Improvement in Quality of Care and Outcomes for Patients Hospitalized With Stroke or Transient Ischemic Attack: Data From The Get With The Guidelines-Stroke Program

Stroke, Ahead of Print. BACKGROUND:The Get With The Guidelines-Stroke program is a quality improvement initiative designed to enhance adherence to evidence-based stroke care. Since its inception in 2003, over 2800 hospitals in the United States have participated in the program.METHODS:We examined patient characteristics, adherence to performance measures, and in-hospital outcomes in patients hospitalized for acute ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack in The Get With The Guidelines-Stroke hospitals from 2003 through 2022. We quantified temporal changes in performance measure adherence and clinical outcomes over time. Performance measure denominators consisted of patients who were eligible, excluding those with contraindications.RESULTS:Over the 20 years of the program, a total of 7837 849 stroke cases (median age 71 years, 51.0% female; 69.2% ischemic strokes, 3.9% SAHs, 11.5% ICHs, and 15.3% TIAs) were entered into the registry. Except for antithrombotics at discharge, in which the baseline performance was >92%, there was sustained improvement in all performance metrics regardless of type of cerebrovascular event (P

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Ottobre 2024

Longitudinal changes in self-reported medication adherence and beliefs about post-stroke medicines in Sweden: a repeated cross-sectional study

Objectives
To explore changes in beliefs about medicines and self-reported medication non-adherence between 3 and 24 months after stroke and to investigate associations between beliefs about medicines and non-adherence at 24 months after stroke.

Design
Longitudinal questionnaire survey.

Setting
Patients treated for acute stroke in 25 Swedish hospitals.

Participants
Only patients living at home were included. Of the 594 individuals who answered the 3 month questionnaire, 401 were included at 24 months; among the remainder, 34 (5.7%) had died, 149 (25,1%) did not respond or had incomplete information on adherence and 10 (1.7%) were not living at home.

Measures
The primary outcome was self-reported medication adherence as measured with the Medication Adherence Report Scale (MARS). The Beliefs about Medicines Questionnaires (BMQ) was used to assess personal beliefs about medicines. Background and clinical data were included from the Swedish national stroke register.

Results
According to dichotomised MARS sum scores, more individuals were classified as non-adherent at 24 months after stroke (n=63, 15.7%) than at 3 months after stroke (n=45, 11.2%) (p=0.030). For BMQ, the only difference over time was an increase in the Necessity subscale (p=0.007). At 24 months, in comparison to adherent patients, non-adherent patients scored statistically significant higher on negative beliefs about medicines, such as Concern (OR 1.17, 95% CI: 1.09 to 1.25), Overuse (OR: 1.37, 95% CI: 1.21 to 1.54) and Harm (OR: 1.24, 95% CI: 1.11 to 1.39), and lower on positive beliefs about medicines, namely, Necessity (OR: 0.88, 95% CI: 0.80 to 0.96) and Benefit (OR: 0.85, 95% CI: 0.74 to 0.98).

Conclusions
Stroke patients‘ beliefs about medicines were associated with adherence, and over time beliefs remained stable across all domains, except for an increased perception of medications as being necessary. Despite this, more patients became non-adherent over time. To counteract non-adherence, interventions targeted to improve intentional adherence as well as non-intentional adherence should be investigated and implemented.

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Ottobre 2024

Treatments, medical expenses and complications of hospital outpatient healthcare associated with stroke in patients with diabetes in China: a retrospective analysis of the Beijing Municipal Medical Insurance Database

Objectives
Diabetes is closely associated with risk of stroke and its adverse sequelae. Approximately 20%–33% of patients with stroke have diabetes. In China, however, it is unclear how stroke affects healthcare utilisation, medications and complications among people with diabetes. This study aimed to analyse the clinical characteristics, treatment options, medical expenses and complications of hospital outpatient healthcare associated with stroke in patients with diabetes in China.

Design
A retrospective, multicentre, observational study.

Setting
Beijing Municipal Medical Insurance Database, with data from 2016 to 2018.

Participants
The study included patients with diabetes whose data included 2016–2018 outpatient medication records and who had Beijing medical insurance. Patients who did not have continuous prescription records for more than 2 months were excluded from the analysis. In total, 2 853 036 people with diabetes were included, and patients who had and did not have a stroke were compared.

Results
In our study, 19.75%–22.30% of patients with diabetes suffered from stroke between 2016 and 2018. The average annual medical cost for a patient diagnosed with diabetes is ¥9606.65, and the cost increases to ¥13 428.39 when diabetes was combined with stroke; thus, stroke increases the medical cost for patients with diabetes by 39.78% (p

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Ottobre 2024