Risultati per: Stroke

Stroke, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.

Objectives
To validate and test the generalisability of the SASKit-ML pipeline, a prepublished feature selection and machine learning pipeline for the prediction of health deterioration after a stroke or pancreatic adenocarcinoma event, by using it to identify biomarkers of health deterioration in chronic disease.

Design
This is a validation study using a predefined protocol applied to multiple publicly available datasets, including longitudinal data from cohorts with type 2 diabetes (T2D), inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and various cancers. The datasets were chosen to mimic as closely as possible the SASKit cohort, a prospective, longitudinal cohort study.

Data sources
Public data were used from the T2D (77 patients with potential pre-diabetes and 18 controls) and IBD (49 patients with IBD and 12 controls) branches of the Human Microbiome Project (HMP), RA Map (RA-MAP, 92 patients with RA, 22 controls) and The Cancer Genome Atlas (TCGA, 16 cancers).

Methods
Data integration steps were performed in accordance with the prepublished study protocol, generating features to predict disease outcomes using 10-fold cross-validated random survival forests.

Outcome measures
Health deterioration was assessed using disease-specific clinical markers and endpoints across different cohorts. In the HMP-T2D cohort, the worsening of glycated haemoglobin (HbA1c) levels (5.7% or more HbA1c in the blood), fasting plasma glucose (at least 100 mg/dL) and oral glucose tolerance test (at least 140) results were considered. For the HMP-IBD cohort, a worsening by at least 3 points of a disease-specific severity measure, the “Simple Clinical Colitis Activity Index” or “Harvey-Bradshaw Index” indicated an event. For the RA-MAP cohort, the outcome was defined as the worsening of the “Disease Activity Score 28” or “Simple Disease Activity Index” by at least five points, or the worsening of the “Health Assessment Questionnaire” score or an increase in the number of swollen/tender joints were evaluated. Finally, the outcome for all TCGA datasets was the progression-free interval.

Results
Models for the prediction of health deterioration in T2D, IBD, RA and 16 cancers were produced. The T2D (C-index of 0.633 and Integrated Brier Score (IBS) of 0.107) and the RA (C-index of 0.654 and IBS of 0.150) models were modestly predictive. The IBD model was uninformative. TCGA models tended towards modest predictive power.

Conclusions
The SASKit-ML pipeline produces informative and useful features with the power to predict health deterioration in a variety of diseases and cancers; however, this performance is disease-dependent.

Introduction
Stroke and vascular cognitive impairment (VCI) are major global public health pandemics. The increased incidence of stroke and VCI is in part due to modifiable risk factors (MRFs), with hypertension (HTN) being the strongest single MRF. Even though the underlying causes of HTN are multifactorial, lifestyle choices (eg, poor diet, physical inactivity, alcohol consumption) are chief contributors. Lifestyle medicine (LSM) is a medical and evidence-based discipline that is a promising approach for preventing stroke and cognitive impairment, including VCI. The empirical evidence from systematic reviews, meta-analyses and large population-based studies has reported on the effectiveness of LSM interventions. However, the evaluation of such complex, social and behavioural interventions warrants more information to allow its successful implementation into innovative clinical care models. More importantly, we need to understand how such interventions work, who it works for and under what circumstances to successfully manage HTN and other MRFs (eg, hyperlipidaemia, smoking, alcohol use and diet).

Methods and analysis
This realist review will follow the Realist and Meta-narrative Evidence Synthesis: Evolving Standards. The review will comprise four stages: (1) clarify the scope, (2) search for the evidence, (3) critically appraise primary studies and extract data focusing on the context, mechanism and outcome configuration and (4) synthesise evidence and draw conclusions.

Ethics and dissemination
Research ethics board approval is not required for this review. The primary output of this review will be an evidence-based programme theory for LSM interventions for the management of HTN and other MRFs to reduce the risk of stroke and VCI. Findings from this review will be disseminated at three levels: micro (eg, patients, caregivers, clinicians, non-research partners), meso (eg, public, national not-for-profit organisations, professional associations and centres) and macro (eg, policymakers and government partners).

PROSPERO registration number
CRD42024511566.

Stroke, Ahead of Print.

Stroke, Ahead of Print. BACKGROUND:Risk models to identify patients at high risk of asymptomatic carotid artery stenosis (ACAS) can help in selecting patients for screening, but long-term outcomes in these patients are unknown. We assessed the diagnostic and prognostic value of the previously published Prevalence of ACAS (PACAS) risk model to detect ACAS at baseline and to predict subsequent risk of stroke and cardiovascular disease (CVD) during follow-up.METHODS:We validated the discrimination and calibration of the PACAS risk model to detect severe (≥70% narrowing) ACAS with patients from the Reduction of Atherothrombosis for Continued Health registry. We subsequently calculated the incidence rates of stroke and CVD (fatal and nonfatal stroke or myocardial infarction or vascular death) during follow-up in 4 risk groups (low, medium, high, and very high, corresponding to sum scores of ≤9, 10–13, 14–17, and ≥18, respectively).RESULTS:Among 26 384 patients, aged between 45 and 80 years, without prior carotid procedures, 1662 (6.3%) had severe baseline ACAS. During ≈70 000 patient-years of follow-up, 1124 strokes and 2484 CVD events occurred. Discrimination of the PACAS model was 0.67 (95% CI, 0.65–0.68), and calibration showed adequate concordance between predicted and observed risks of severe baseline ACAS after recalibration. Significantly higher incidence rates of stroke (Ptrend

Introduction
Aphasia is a common dysfunction among patients with stroke that can severely affect daily life. Listening to the ‘five-tone’ melodies of traditional Chinese medicine can improve some of the language functions of patients with post-stroke aphasia; however, passive listening may limit its clinical efficacy. In this study, we transform the passive listening five-tone melodic therapy of traditional Chinese medicine into an active five-tone speech therapy. This randomised controlled trial aims to investigate the clinical efficacy of active five-tone speech therapy in the treatment of post-stroke aphasia, such as language function, daily communication ability and communication efficiency, as well as investigate the therapeutic mechanism of this innovative therapy by electroencephalogram and MRI.

Methods and analysis
The study is a multicentric, randomised, parallel-assignment, single-blind treatment study. 70 participants will be recruited from the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine and the Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine and randomly assigned to two groups, the five-tone speech therapy group and the control group, at a 1:1 ratio. The control group will receive 20 sessions of conventional speech-language therapy, while the five-tone speech therapy group will receive 20 sessions of five-tone speech therapy in addition to conventional speech-language therapy. The primary outcome measure for this study will be the score on Western Aphasia Battery. Secondary outcomes include communicative abilities in daily living, percentage of correct information units and correct information units per minute, as well as resting-state electroencephalogram, event-related potentials and MRI data. All outcomes will be evaluated at 0 weeks (before intervention) and at 4 weeks (after 20 intervention sessions).

Ethics and dissemination
Ethical approval of this study was granted by the ethics committees of the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine (2023KY-009-01) and the Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine (2023-kl-010). Recruitment commenced on 24 April 2023. Informed consent will be obtained from all participants of the trial (or from their legal guardians, where applicable). The outcomes of the trial will be disseminated through peer-reviewed publications.

Trial registration number
ChiCTR2300069257.

Stroke, Volume 55, Issue 10, Page 2462-2471, October 1, 2024. BACKGROUND:Ischemic stroke (IS) represents a significant health burden globally, necessitating a better understanding of its genetic underpinnings to improve prevention and treatment strategies. Despite advances in IS genetics, studies focusing on the Spanish population and sex-stratified analyses are lacking.METHODS:A case-control genome-wide association study was conducted with 9081 individuals (3493 IS cases and 5588 healthy controls). IS subtypes using Trial of ORG 10172 in Acute Stroke Treatment criteria were explored in a sex-stratified approach. Replication efforts involved the MEGASTROKE, GIGASTROKE, and the UK Biobank international cohorts. Post-genome-wide association study analysis included: in silico proteomic analysis, gene-based analysis, quantitative trait loci annotation, transcriptome-wide association analysis, and bioinformatic analysis using chromatin accessibility data.RESULTS:Identified as associated with IS and its subtypes were 4 significant and independent loci. Replication confirmed 5p15.2 as a new locus associated with small-vessel occlusion stroke, with rs59970332-T as the lead variant (beta [SE], 0.13 [0.02];P=4.34×10−8). Functional analyses revealedCTNND2given proximity and its implication in pathways involved in vascular integrity and angiogenesis. Integration of Hi-C data identified additional potentially modulated genes, and in silico proteomic analysis suggested a distinctive blood proteome profile associated with the lead variant. Gene-set enrichment analyses highlighted pathways consistent with small-vessel disease pathogenesis. Gene-based associations with known stroke-related genes such asF2andFGGwere also observed, reinforcing the relevance of our findings.CONCLUSIONS:We foundCTNND2as a potential key molecule in small-vessel occlusion stroke risk, and predominantly in males. This study sheds light on the genetic architecture of IS in the Spanish population, providing novel insights into sex-specific associations and potential molecular mechanisms. Further research, including replication in larger cohorts, is essential for a comprehensive understanding of these findings and for their translation to clinical practice.

Stroke, Volume 55, Issue 10, Page 2522-2527, October 1, 2024. BACKGROUND:The discrepancy between experimental research and clinical trial outcomes is a persistent challenge in preclinical studies, particularly in stroke research. A possible factor contributing to this issue is the lack of standardization across experimental stroke models, leading to poor reproducibility in multicenter studies. This study addresses this gap by aiming to enhance reproducibility and the efficacy of multicenter studies through the harmonization of protocols and training of involved personnel.METHODS:We established a set of standard operating procedures for various stroke models and the Neuroscore. These standard operating procedures were implemented across multiple research centers, followed by specialized, in-person training for all participants. We measured the variability in infarct volume both before and after the implementation of these standardized protocols and training sessions.RESULTS:The standardization process led to a significant reduction in variability of infarct volume across different stroke models (40%–50% reduction), demonstrating the effectiveness of our harmonized protocols and training. Additionally, the implementation of the Neuroscore system across centers showed low variability and consistent results up to 28 days poststroke, underscoring its utility in chronic phase evaluations.CONCLUSIONS:The harmonization of protocols and surgeon training significantly reduced variability in experimental outcomes across different centers. This improvement can increase the comparability of data between research groups and enhance the statistical power of multicenter studies. Our findings also establish the Neuroscore as a reliable tool for long-term assessment in stroke research, paving the way for more consistent and impactful multicenter preclinical studies.

Stroke, Volume 55, Issue 10, Page 2401-2401, October 1, 2024.

Stroke, Volume 55, Issue 10, Page e271-e272, October 1, 2024.

Stroke, Volume 55, Issue 10, Page 2431-2438, October 1, 2024. BACKGROUND:Branch atheromatous disease (BAD)–related stroke has emerged as a meaningful subtype of ischemic stroke yet remained understudied. We aimed to investigate the demographic, clinical, therapeutic, and prognostic characteristics of BAD-related stroke.METHODS:The BAD-study was a nationwide, multicenter, prospective, observational cohort study in 20 Chinese hospitals from June 2021 to June 2023, enrolling patients aged 18 to 80 years with BAD-related stroke within 72 hours of onset. Eligible single subcortical infarct in the territory of lenticulostriate artery and paramedian pontine artery was included. Clinical, laboratory, and treatment data were collected at baseline. The primary outcome was a proportion of good outcomes (modified Rankin Scale score, 0–2) at 90 days. Main secondary outcomes included early neurological deterioration (END), cerebrovascular event, major bleeding, and excellent outcome (modified Rankin Scale score, 0–1) during 90-day follow-up.RESULTS:We finally enrolled 476 patients, with a median age of 60 (interquartile range, 53–68) years, and 70.2% were male. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 2–6) at enrollment. Involvement of the lenticulostriate artery was more common than the paramedian pontine artery (60.7% versus 39.3%). END occurred in 14.7% of patients, with a median time from onset of 38 (interquartile range, 22–62) hours. The rates of good and excellent outcomes were 86.5% and 72%, respectively. Its 90-day stroke recurrence rate was 1.9%. Acute-phase therapy (from onset to 7 days of enrollment) showed heterogeneity and was not associated with prognosis. Multivariable logistic regression analysis identified the National Institutes of Health Stroke Scale score ≥4 at admission and END as negative predictors and extracranial artery stenosis as a positive predictor of good outcomes. Age ≥60 years, National Institutes of Health Stroke Scale score ≥4 at admission, and END were negative predictors of excellent outcomes.CONCLUSIONS:With distinct demographic, clinical, and prognostic characteristics, along with a high incidence of END and a low risk of stroke recurrence, BAD-related stroke could be categorized as a separate disease entity. Moreover, its acute-phase treatment strategies were undetermined, awaiting further high-quality studies.

Stroke, Volume 55, Issue 10, Page 2567-2572, October 1, 2024. In the 2024 David G. Sherman Lecture, Steven J. Warach, illustrating with examples from his research, walks through the history of magnetic resonance imaging in acute stroke from the 1990s and early 2000s with the introduction, validation, and application of diffusion-weighted imaging, penumbral imaging (the diffusion-perfusion mismatch), and other imaging markers of the acute stroke pathology into routine clinical practice and stroke trials. The adaptation of diffusion-weighted imaging for clinical scanners in the acute hospital setting began a revolution in ischemic stroke diagnosis as the presence, location, and size of ischemic lesions could now be visualized at the earliest times after stroke onset when computed tomography and conventional magnetic resonance imaging still appeared normal. In combination with perfusion magnetic resonance imaging, diffusion-weighted imaging made imaging of the ischemic penumbra a practical reality for routine clinical use and feasible for integration as a selection tool into clinical trials. It was apparent from the initial use of diffusion-perfusion imaging in acute stroke that many patients had persistence of penumbra as late as 24 hours after stroke onset although the probability of penumbra decreased over time. The therapeutic time window for ischemic stroke selected by clinical and temporal criteria reflected the decreased proportion of patients with the therapeutic target over time rather than the absence of the penumbral target in all patients at later times. This work provided the empirical and conceptual framework for the shift toward selection and evaluation of patients for acute stroke therapies based on direct observation of the target pathology and away from the exclusive dependence on clinical and temporal surrogates to infer the presence of stroke therapeutic targets, a shift that has expanded the indications for acute reperfusion therapies over the last 10 years.

Introduction
Several systematic reviews and meta-analyses (SRs/MAs) of clinical trials showed the efficacy of acupuncture for post-stroke motor impairment. To systematically estimate and synthesise these results, we aimed to conduct an overview of SRs/MAs to summarise the evidence and evaluate the methodological quality regarding the effectiveness and safety of acupuncture for post-stroke motor impairment.

Methods and analysis
This is a protocol for an overview of SRs/MAs. A literature search will be conducted in PubMed, Embase, Web of Science and Cochrane Central Registry of Controlled Trials from the construction of the database to March 2024. SRs/MAs evaluating the efficacy of acupuncture in post-stroke motor impairment patients will be included. Two independent investigators will screen and evaluate related SRs/MAs back-to-back. We will extract data into a predefined form designed to summarise the key characteristics of each study. The evaluation of methodological quality of the included SRs/MAs will be assessed using AMSTAR-2, the PRISMA 2020 checklist and the GRADE grading system.

Ethics and dissemination
Ethics approval is not required for this overview as we will only analyse published literature. The results will be published in a peer-reviewed journal.

PROSPERO registration number
CRD42024502006.

Introduction
Stroke is a common cause of death and disability in the older adult and increases the risk and severity of cognitive impairment, which is a factor for long-term death among stroke survivors. Some studies have focused on the effects of reminiscence therapy with different media on stroke survivors. It is currently unclear which is the best medium. This protocol aims to deal with this problem by using a network meta-analysis.

Methods and analysis
Published randomised controlled trials will be included if reminiscence therapy plus usual care was applied in older adult patients who had a stroke in the experimental group and usual care was applied in the control group. Six electronic databases will be searched from their inception to August 2023, including the Cochrane Library, CINAHL, PubMed, Web of Science, Medline and Embase. The media of reminiscence therapy may include (but not restricted to) old photos, music or movies. Outcomes will be cognitive function and negative moods. Study selection, data extraction and quality assessment will be performed independently by two reviewers. The risk of bias (RoB) of the included studies will be evaluated in accordance with the Cochrane Collaboration’s RoB tool. The evidence quality will be measured based on the Grading of Recommendations Assessment, Development and Evaluation. To compare the efficacy of reminiscence therapy with different media, standard pairwise meta-analysis and Bayesian network meta-analysis will be conducted. The probabilities of intervention for all outcomes will be ranked based on the surface under the cumulative ranking curve.

Ethics and dissemination
Ethical approval is not required for reviewing published studies. The findings will be submitted to a peer-reviewed journal for review and publication to provide important evidence for clinicians and guideline developers to determine interventions for older adult patients who had a stroke.

PROSPERO registration number
CRD42023447828.