Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 79 appraisals
Brain and behavior
Machine Learning-Based Prediction of Poor Outcomes in Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis
BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is associated with high risks of mortality and disability, yet early and accurate outcome prediction remains challenging. This study systematically evaluated the performance of machine learning (ML) models in predicting key adverse outcomes (hematoma expansion [HE], poor functional outcome, mortality) in ICH, aiming to provide consolidated evidence for future research and clinical translation. METHODS: We systematically searched PubMed, Embase, Web of Science, and Cochrane Library up to September 2025. Studies developing and validating ML models for predicting HE, poor functional outcome (modified Rankin Scale 3-6), or mortality in adults with spontaneous ICH were included. Pooled concordance index (C-index), sensitivity, and specificity were calculated using a random-effects or bivariate model. RESULTS: Eighty-three studies (involving at least 136,840 patients) were included. Meta-analysis of model performance, derived predominantly from internal validation set, demonstrated that models integrating both clinical and radiomics features achieved the highest discriminative performance across key prognostic prediction tasks: predicting HE (pooled C-index 0.822, 95% confidence interval [CI] 0.789-0.855), poor functional outcome (C-index 0.850, 95% CI 0.830-0.869), and mortality (C-index 0.860, 95% CI 0.809-0.911). These findings should be interpreted with caution, as true external validation remains sparse. Logistic regression exhibited performance comparable to more complex ML algorithms. CONCLUSIONS: ML models, particularly integrated clinical-radiomics models, demonstrate strong performance for the prediction of outcomes in ICH. They hold significant potential to enhance risk stratification and guide personalized management, pending further validation in diverse cohorts.
1 Aug 2026
Read appraisal →International journal of medical informatics
Machine learning models for predicting readmission after stroke: A systematic review and meta-analysis
BACKGROUND: Hospital readmission following stroke poses a significant challenge for healthcare systems. Machine learning (ML) offers the potential to improve prediction models for readmission risk, surpassing traditional statistical methods. However, the performance of ML models in such context has not been systematically evaluated. We aim to evaluate the performance of ML models in predicting post-stroke hospital readmission, as well as identifying the most important readmission predictors. METHODS: A comprehensive systematic literature review and meta-analysis was conducted.Studies included were those utilizing ML models for stroke readmission prediction. The primary outcome was the predictive performance of ML models for all time stroke readmission as reported by the Area Under the Receiver Operating Characteristic Curve (AUROC). Pooled AUROC values were calculated using a random-effects model. RESULTS: A total of eleven studies involving 380,254 patients were analyzed. Mean age of the patients ranged between 64.5 and 79.7 years. In total, 49 ML models were reported with Logistic regression (LR) and Random Forest being the most used. The number of input predictive variables used for model training ranged from 6 to 10,047. The overall pooled AUROC for predicting hospital readmission was 0.74 (95% CI: 0.69 to 0.78). For 30-day readmission, the pooled AUROC was 0.73 (95% CI: 0.67 to 0.79) while for 90-day readmission, it was 0.75 (95% CI: 0.69 to 0.80). The most frequently reported variables as being top predictors of readmission were Length of stay (LOS) (3 studies), Age (2 studies), National Institutes of Health Stroke Score (NIHSS) (2 studies), HbA1c (2 studies), Homocysteine blood level (2 studies). CONCLUSION: Machine learning models demonstrate moderate predictive performance in stroke readmission risk prediction. Future research should focus on validating and refining existing models and adopting unified methodological approaches to aid in drawing more accurate conclusions.
1 Aug 2026
Read appraisal →Biomedical physics & engineering express
EEG-EMG spatiotemporal cross-attention fusion network for functional upper-limb movement classification
Objective. Electroencephalography (EEG) and electromyography (EMG) are widely used for decoding motor intentions, yet unimodal approaches often suffer from low robustness and limited representational information. EEG-EMG hybrid brain-computer interfaces (BCIs) can bridge cortical intention and muscular execution, but challenges remain in signal alignment, fusion modeling, and clinical generalization.Approach. To address these issues, we propose spatio-temporal cross-attention fusion (STCAFusion), a spatiotemporal cross-attention (CA) framework that integrates EEG and EMG through multi-band based dual-branch convolutional encoders and parallel temporal and spatial CA modules. This design enables detailed modeling of inter-modal correlations across both time and space. We evaluate STCAFusion on a newly collected dataset of synchronous EEG-EMG recordings from 12 subjects, where the data were acquired under two paradigms (Reaching and Lifting) designed from daily functional upper-limb activities to emphasize directional and strength control.Main results. With leave-one-run-out cross-validation, STCAFusion achieves average accuracies of 84.15% and 95.22% in the two paradigms, outperforming the strongest competing EEG-EMG fusion baselines by 3.4% in the Reaching paradigm and 1.8% in the Lifting paradigm. Visualization of learned attention weights further reveals meaningful spatiotemporal EEG-EMG coupling patterns, offering insights into neural-muscular coordination patterns relevant to rehabilitation-oriented BCI design.Significance. These results highlight the potential of CA-based multimodal physiological signal fusion in building reliable hybrid BCI and wearable devices for upper-limb control and rehabilitation.
14 July 2026
Read appraisal →Journal of molecular neuroscience : MN
Scalp Acupuncture Combined with Mouse Nerve Growth Factor Acupoint Injection for Post-stroke Cognitive Impairment
Post-stroke cognitive impairment (PSCI) markedly impairs rehabilitation efficacy and quality of life. Safe and effective interventions are urgently needed. Eighty-four patients with PSCI were randomly allocated into three groups (n = 28 per group). Group A received conventional cognitive training. Group B received conventional training plus scalp acupuncture. Group C received the treatment of Group B combined with mouse nerve growth factor (mNGF) acupoint injection. All interventions lasted 4 weeks. All groups exhibited significant within-group improvements in MoCA, ADL, MBI, and FMA scores after intervention. Group C achieved the optimal cognitive efficacy: the post-treatment MoCA score was 26.7 ± 2.9 (95% CI, 25.53-27.87), significantly higher than that in Group A (21.5 ± 3.5 (95% CI, 20.22-22.78), P < 0.001) and Group B (23.8 ± 3.2)(95% CI, 22.48-25.12), P = 0.003). The ADL score in Group C was the lowest among the three groups (F = 28.963, P < 0.001), suggesting better independence. Moreover, motor function (FMA) and basic self-care ability (MBI) were also significantly improved in all groups after intervention. There were significant inter-group differences in post-treatment FMA and MBI scores (F-FMA = 29.745, P < 0.001; F-MBI = 35.872, P < 0.001). The scores increased gradually from Group A to Group C, with Group C achieving the best improvement. Conventional cognitive training improves cognitive function and daily living ability in patients with PSCI. Scalp acupuncture combined with conventional training is more effective than training alone. The triple therapy of conventional training, scalp acupuncture, and mNGF acupoint injection further enhances rehabilitation outcomes, with prominent clinical application value.
13 July 2026
Read appraisal →Neurosurgical review
Mechanical thrombectomy for pediatric large-vessel occlusion: a systematic review and meta-analysis with post hoc analysis
OBJECTIVE: To investigate the outcome of pediatric large vessel occlusion (LVO) treated with mechanical thrombectomy (MT). INTRODUCTION: Pediatric LVO is a rare subtype of ischemic stroke. In adults, MT is recommended; however, the efficacy and safety of MT in pediatric LVO are less explored. The available studies are mostly observational studies; yet, these studies show inconsistent findings. METHOD: This review adhered to the PRISMA 2020 guideline. Studies comparing MT with medical management in pediatric with LVO were included. The primary endpoint was the favourable outcome. The mortality rate was sought as well. Subgroup analysis compared MT with intravenous thrombolysis (IVT) and conservative management. Post hoc exploratory analyses comprised Bayesian inference and trial sequential analysis (TSA). RESULT: Six studies comprising a total of 230 MT-treated and 206 non-MT patients were included. In the primary analysis, favourable outcome did not differ significantly between the MT and medical management groups (OR 1.83; 95% CI 0.97-3.43), while supported by exploratory Bayesian inference (OR 1.75; 95% CrI 1.05-2.67; BF10 5.05). Subgroup analysis showed favourable outcomes of MT over IVT (OR 2.39; 95% CI 1.19-4.79) and conservative treatment (OR 2.22; 95% CI 1.41-3.51), although the Bayesian model did not support these findings. The available evidence was insufficient to detect or exclude a difference in mortality between MT and medical management (OR 1.32; 95% CI 0.45-3.89). TSA indicated that the required information size was not reached and that additional trials are needed to reach the minimum sample requirements. CONCLUSION: In this synthesis of observational data, the MT may be associated with favourable outcome in pediatric LVO, however, these findings are hypothesis-generating only. Adequately powered prospective studies are needed before MT can be recommended for pediatric LVO. CLINICAL TRIAL NUMBER: not applicable.
13 July 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Combined transcranial direct current stimulation and mirror therapy for upper limb rehabilitation in patients with stroke: a systematic review and meta-analysis
Upper limb impairment is among the common consequences of stroke. Combining transcranial direct current stimulation (tDCS) and mirror therapy (MT) have recently been used to improve neural plasticity and functional recovery. This review aims to evaluate the effects of combined tDCS and MT on upper limb function in patients with stroke. "PubMed, Scopus, Web of Science, CINAHL, PEDro, and EMBASE" were searched from their inception to March 2026. Randomized controlled trials investigating the combination of tDCS and MT in patients with stroke and assessing upper limb function were included. The quality and the certainty of evidence were evaluated. Seven studies (454 participants) met the eligibility criteria. Significant improvements were demonstrated in upper limb motor function (SMD = 0.73, 95% CI 0.34 to 1.12, p = 0.0002), activities of daily living (SMD = 0.84, 95% CI 0.46 to 1.22, p < 0.0001), and neurophysiological outcomes reflecting corticospinal conduction efficiency, assessed using central motor conduction time (CMCT) (SMD = -1.26, 95% CI -1.60 to -0.92, p < 0.0001). Subgroup analysis demonstrated greater effects in subacute stroke (SMD = 1.03, 95% CI 0.73 to 1.33). Other outcomes reported improvements in hand function and grip strength. Preliminary evidence suggests that combining tDCS and MT may improve upper limb motor and functional outcomes after stroke; however, these findings should be interpreted with caution due to heterogeneity and the limited data. Further studies are strongly needed.
11 July 2026
Read appraisal →Translational stroke research
Quantitative Cerebrovascular Analysis for Improved Prediction of Post-Stroke Complications
Endovascular thrombectomy (EVT) has transformed the treatment of acute ischemic stroke (AIS). However, a substantial proportion of AIS patients experience poor outcomes despite successful recanalization, often due to severe neurological deterioration or life-threatening complications. Early identification of these high-risk patients remains a major unmet need. In this study, we developed and validated machine-learning (ML) models that integrate automated quantitative brain arterial morphology and collateral grading with demographic, clinical, laboratory, and imaging variables to predict major post-EVT complications and early neurological outcomes. Using a prospectively collected database of 727 AIS patients that underwent EVT, we developed ML models to incorporate patient-specific vascular morphometry with conventional clinical, laboratory, and imaging data to predict emergence of early neurological deterioration (END), symptomatic intracranial hemorrhage (sICH), malignant brain edema (MBE) requiring surgical decompression, and neurogenic respiratory failure and dysphagia requiring tracheostomy/gastrostomy (TC/PEG). Our analysis of morphological features, including increased tortuosity and reduced vessel diameter, showed strong associations with complications. Morphology-informed (MI) models consistently outperformed baseline-clinical (BC) models for patients with END (AUROC 0.81 for MI model vs. 0.73 for BC), sICH (AUROC 0.68 MI vs. 0.56 BC model), MBE (AUROC 0.67 MI model vs. 0.56 BC), or patients who underwent TC/PEG (AUROC 0.66MI vs. 0.58 BC model). Statistical testing confirmed significant AUROC improvements for END, sICH and mRS (p < 0.05), Finally, patient-specific calibrated probability profiles enabled individualized, multidimensional risk stratification, revealing distinct complication-specific risk patterns across patients. These findings demonstrate that cerebrovascular structure-an often overlooked yet physiologically fundamental determinant of ischemic injury and reperfusion dynamics-provides significant predictive information that is not captured by standard clinical or visual imaging assessments. Automated vascular segmentation and collateral grading techniques enable rapid and objective integration of cerebrovascular metrics into prognostic models, offering a scalable tool for precision risk stratification, supporting earlier intervention, targeted monitoring, and improved post-EVT management.
9 July 2026
Read appraisal →PloS one
Effects of immersive virtual reality on limb motor function, balance, gait and quality of life after stroke: A systematic review and meta-analysis
Immersive virtual reality (IVR) has been increasingly integrated into stroke rehabilitation albeit the effectiveness across different outcome domains remains unclear. This study aimed to review evidence from randomized controlled trials evaluating the effects of IVR, used alone or in combination with conventional rehabilitation, on motor-, functional-, and participation-related outcomes after stroke. Ovid MEDLINE, Embase, Cochrane Library and CINAHL were screened up to April 2025 to identify eligible randomized controlled trials (RCTs). A systematic literature search was conducted. Randomized controlled trials including adults with stroke and evaluating immersive virtual reality interventions were eligible. Studies using non-immersive VR, non-randomized designs, or not reporting motor, functional, or participation outcomes were excluded. Meta-analyses were performed where data were sufficiently homogeneous; otherwise, outcomes were summarized descriptively. Risk of bias was assessed using standardized appraisal tools, and certainty of evidence was evaluated using the GRADE approach. Out of 3,574, we included 34 RCTs involving post-acute, subacute and chronic stroke survivors, with a total of1200 participants. Meta-analyses showed IVR, most commonly delivered in combination with conventional rehabilitation, to be associated with improvements in upper extremity motor impairment, particularly measured by the Fugl-Meyer Assessment Upper Extremity (FMA-UE). Small but significant effects were also found for selected gait parameters. In contrast, effects on functional performance, balance, and quality of life were inconsistent and could not be robustly quantified. The overall certainty of evidence ranged from low to very low, primarily due to heterogeneity, methodological limitations, and small sample sizes. In conclusion, IVR appears to be a promising and safe supplement to conventional stroke rehabilitation, particularly for improving motor impairment. However, evidence remains limited and inconsistent across functional outcomes. More well-designed, adequately powered trials with standardized interventions and clinically meaningful outcome measures are needed to clarify the role of IVR in stroke rehabilitation. PROSPERO (Registration number: CRD420250639792).
7 July 2026
Read appraisal →Brain impairment : a multidisciplinary journal of the Australian Society for the Study of Brain Impairment
Rehabilitation technologies perceived positively by patients and facilitated intensive therapy within sessions.
BACKGROUND: Australian inpatient rehabilitation facilities are increasingly integrating rehabilitation technologies to support patient recovery. However, little is known about patient perceptions of rehabilitation technologies and the intensity of therapy able to be facilitated. This study aimed to quantify the amount of practice being achieved by patients in an Australian inpatient rehabilitation setting and explore their perceptions of upper limb rehabilitation technologies. METHODS: A multimethod study design was used to investigate the perceptions and use of rehabilitation technologies (i.e. InMotion, Fourier ArmMotus, SaeboReJoyce and Touch Accessible Platform for Interactive Technology) by adult inpatients. Semi-structured interviews and the System Usability Scale were completed. Observations of routine therapy sessions were undertaken to quantify the amount and intensity of technology-based practice. RESULTS: Ten participants were recruited (50% male, mean age 62 years). A total of 15 sessions were observed across all participants using robot-assisted therapy and Touch Accessible Platform for Interactive Technology at an average duration of 35 min/session; of which 29 min was active therapy. Most participants described their experiences with rehabilitation technologies positively, highlighting benefits for recovery, enjoyability and easy usability. Participants rated the technologies highly on the System Usability Scale, with total scores ranging between 65 and 100 for usability, and a minimum rating of 'good' for user-friendliness. CONCLUSION: Rehabilitation technologies were well received by adults undergoing inpatient rehabilitation and with application for a range of impairments. The technologies facilitated enjoyment of daily therapy, and participants were comfortable with limited therapist input when using the devices. Additionally, participants were able to engage in highly intensive practice using the technologies.
27 June 2026
Read appraisal →Progress in biomedical engineering (Bristol, England)
Assessing the relevance of biosignal-controlled robotic rehabilitation technologies: a systematic review.
Technology is transforming rehabilitative medicine by enhancing accessibility and personalisation. Robot-assisted rehabilitation uses robotic systems for recovery from physical and neurological impairments, enabling intensive, repetitive training with real-time feedback. These systems aim to restore motor function and mobility and to increase independence in daily life, needs that are growing in light of population ageing. Rather than revisiting control algorithms or mechanical design, this review aims to investigate the combined use of bio-signals and robotic rehabilitation systems, and to discuss their potential in rehabilitation settings outside disease-specific clinical frameworks. We reviewed studies published from 2020 through early 2025 to capture recent advances in this rapidly evolving field. Our objective was to assess the relevance of these technologies to rehabilitation outcomes, such as improvements in motor function or other clinical metrics. We considered robot-assisted systems driven by biosignals such as electromyography (EMG), electroencephalography, or electrocardiography and included only studies reporting measurable rehabilitative outcomes. Following PRISMA guidelines, we searched Scopus, PubMed, and WoS databases. Of 207 records screened, 15 met the inclusion criteria. Overall, the included studies suggest that contemporary biosignal-controlled robotic rehabilitation, particularly EMG-driven approaches, may support more intensive, personalised, and engaging therapy than conventional care alone, although the current evidence remains preliminary. Preliminary findings indicate that, by closing the loop among patient, device, and therapist, these systems may reduce muscle activity and support improvements in motor performance; however, the evidence base remains heterogeneous and generally underpowered. To support future clinical adoption, the field needs adequately sized, head-to-head trials with standardised outcome measures, longer follow-up, and transparent reporting of adherence, adverse events, user experience, and implementation barriers, including training and cost. These steps will be important to further assess efficacy and evaluate usability in real-world settings.
20 June 2026
Read appraisal →Journal of neurology, neurosurgery, and psychiatry
Clinically reported covert cerebrovascular disease and risk of neurological disease: a whole-population cohort of 367 988 people using natural language processing
BACKGROUND: The relevance of covert cerebrovascular disease (CCD) in practice is uncertain, partly because estimation of risk in whole clinical populations is difficult. Studies have had success extracting CCD from clinical text using natural language processing (NLP), though they have been limited to specific CCD phenotypes. Here, we used NLP to measure multiple clinically-reported CCD phenotypes in a large clinical cohort and estimated subsequent disease risk in health record data. METHODS: From all people with brain imaging in Scotland (2010-2018), we selected people with no prior hospitalisation for neurological disease (n=367 988). NLP of imaging reports identified: white matter hypoattenuation or hyperintensities (WMH), lacunes, cortical infarcts and cerebral atrophy. Adjusted HRs (aHRs) were estimated between each phenotype and stroke, dementia and Parkinson's disease (conditions previously associated with CCD), epilepsy and colorectal cancer (control conditions). RESULTS: For each phenotype, the aHR of stroke was WMH 1.4 (95% CI 1.3-1.4), lacunes 1.6 (1.5-1.6), cortical infarct 1.8 (1.7-1.9) and cerebral atrophy 1.1 (1.0-1.1). The aHR of dementia was WMH 1.3 (1.3-1.3), lacunes 1.0 (0.9-1.0), cortical infarct 1.1 (1.1-1.2) and cerebral atrophy 1.7 (1.7-1.8). The aHR of Parkinson's disease was WMH 1.1 (1.0-1.2), lacunes 1.1 (0.9-1.2), cortical infarct 0.7 (0.6-0.9) and cerebral atrophy 1.4 (1.3-1.5). The aHRs between CCD phenotypes and epilepsy and colorectal cancer were around the null. CONCLUSION: CCD and atrophy have implications for future disease risk and can be identified at scale using NLP of clinical reports. Prevention of neurological disease in people with CCD should be a priority for healthcare policy makers.
14 June 2026
Read appraisal →Journal of neurology, neurosurgery, and psychiatry
Impact of an artificial intelligence-driven triage system on workflow and transfer efficiency: stratified analysis of 4548 admissions to four thrombectomy hubs receiving transfers from sixty spokes.
BACKGROUND: We aimed to evaluate the impact of implementing an artificial intelligence (AI)-enabled acute ischaemic stroke triage system on workflow efficiency and transfer optimisation in a large academic healthcare network. METHODS: A prospectively maintained database was reviewed comparing equivalent time periods before and after AI-enabled triage platform implementation (January 2021-December 2022). The primary analysis compared workflow metrics between AI-enabled and non-AI spokes during the same calendar period (2022) to control for temporal confounding. Benjamini-Hochberg correction was applied for multiple comparisons, and analyses were adjusted for age and baseline National Institutes of Health Stroke Scale. Evaluated outcomes included door-in-door-out (DIDO) times, door-to-puncture (DTP) times, endovascular therapy (EVT) utilisation rates, cost analysis and clinical outcomes at discharge. RESULTS: The study included 4548 admissions with 844 EVT patients (394 pre-implementation, 450 post-implementation) across four hub centres. In the primary same-period analysis (2022), AI-enabled spokes demonstrated significantly shorter DIDO times compared with non-AI spokes (median 103 (92-118) vs 134 (103-162) min; adjusted difference -41.6 min (95% CI -60.9 to -24.1); p<0.001, Q<0.001) and shorter DTP times (21 (14-43) vs 40 (18-65) min; adjusted difference -10.9 min (95% CI -17.9 to -3.7); p=0.003, Q=0.009). A difference-in-differences analysis demonstrated that DIDO improvements were specific to AI-enabled spokes (-27 min; 95% CI -62 to -4; p=0.029). EVT utilisation was also significantly higher in AI-enabled versus non-AI spokes where AI-enabled spokes had increased EVT rates by +17.8% (39.3% to 57.1%) compared with +1.1% in non-AI spokes (41.3% to 42.4%, Pinteraction=0.006). DTP improvements were more pronounced at community hubs (86 (48-108) to 51 (22-77) min; adjusted difference -24.9 min; p=0.021, Q=0.041) compared with academic hubs (60 (23-87) to 55 (22-73) min; adjusted difference -15.5 min; p<0.001, Q=0.002). Subgroup analyses demonstrated consistent DIDO benefits across age, stroke severity and sex strata with no significant treatment effect heterogeneity (all P-interaction >0.05). Probabilistic cost analysis estimated savings of $3.6 million (95% CI $1.5M to $6.1M) per 1000 AI-enabled spoke transfers. Clinical outcomes, including functional status and mortality at discharge, were similar between groups (all Q>0.05). CONCLUSION: Implementation of an AI-enabled triage platform was associated with significant reductions in workflow times and increased EVT utilisation, with effects specific to AI-enabled spokes rather than secular trends alone. The proportion of transfers who did not proceed to EVT decreased in AI-enabled spokes, though counterfactual outcomes for non-transferred patients remain unknown. Clinical outcomes at discharge were unchanged.
14 June 2026
Read appraisal →Translational stroke research
AI-Guided Patient-Derived Endothelial Modeling Identifies a Reversible Moyamoya-Specific miRNA Deficiency Corrected by Stem Cell-Extracellular Vesicles
Moyamoya disease (MMD) is a progressive cerebrovascular disorder characterized by abnormal vascular remodeling and impaired angiogenesis. We profiled plasma extracellular vesicle (EV)-derived microRNAs (miRNAs) from MMD patients and healthy controls and generated patient-specific induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) to investigate disease-associated molecular alterations and therapeutic reversibility. Both plasma EVs and iPSC-ECs from MMD patients showed significant depletion of angiogenesis-related miRNAs. Small RNA sequencing data revealed mesenchymal stem cell-derived EVs (MSC-EVs) contain a miRNA repertoire that substantially overlaps with miRNAs deficient in MMD. Treatment of MMD iPSC-ECs with MSC-EVs restored the majority of the depleted miRNAs to normal levels, normalized predicted target mRNA expression, and rescued angiogenic function in a dose-dependent manner, as demonstrated by tube formation assays. To improve identification of biologically relevant miRNA-mRNA interactions, we developed an artificial intelligence-based framework integrating experimentally validated databases, endothelial-focused literature mining, and large language model (LLM)-assisted mechanistic scoring. Incorporation of LLM-derived contextual features modestly improved prediction performance compared with conventional sequence-based models (baseline AUROC ~ 0.51; LLM-enhanced AUROC ~ 0.72), suggesting that literature-informed biological context provides meaningful signal beyond structural target features alone. Furthermore, our findings demonstrate that MSC-EV therapy can substantially reverse molecular and functional endothelial deficits. Integrated profiling and AI-driven interaction mapping together establish a hypothesis-generating framework ("Exo-Courier") for biologically informed prioritization of EV-based therapeutic targets in vascular disorders.
12 June 2026
Read appraisal →Translational stroke research
Transcarotid Artery Revascularization for Asymptomatic Carotid Stenosis: A Systematic Review and Meta-Analysis
Management of asymptomatic carotid stenosis remains controversial despite advances in contemporary best medical therapy. Transcarotid artery revascularization (TCAR) has been introduced as an alternative revascularization option alongside carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TF-CAS). Evidence focused specifically on asymptomatic carotid disease, however, remains limited and is derived mainly from observational analyses of clinical databases, with only a small amount of single-center retrospective evidence. The present study therefore examined the available comparative evidence on TCAR for asymptomatic carotid stenosis. A systematic review and meta-analysis was performed of studies reporting outcomes of TCAR in asymptomatic carotid stenosis. Eligible studies included asymptomatic cohorts or mixed populations with extractable asymptomatic subgroup data and reported outcomes after TCAR with comparison against CEA and/or TF-CAS. The primary pooled outcomes were stroke, death, stroke or death, and myocardial infarction at 30 days, together with the corresponding stroke, death, and stroke or death outcomes at approximately 1 year. For TCAR versus CEA, no significant between-group differences were identified in the pooled 30-day risks of stroke (risk ratio (RR), 1.25; 95% CI, 0.98-1.59; I²=82%), death (RR, 0.94; 95% CI, 0.64-1.38; I²=57%), or stroke or death (RR, 1.10; 95% CI, 0.95-1.26; I²=75%). In contrast, myocardial infarction within 30 days occurred less frequently after TCAR (RR, 0.68; 95% CI, 0.48-0.96; I²=71%). At approximately 1 year, pooled estimates likewise showed no significant difference in stroke (RR, 1.27; 95% CI, 0.70-2.29; I²=0%) or death (RR, 1.14; 95% CI, 0.97-1.35; I²=0%), whereas the pooled estimate for stroke or death favored CEA (RR, 1.25; 95% CI, 1.15-1.36; I²=31%). A different pattern emerged in the TCAR versus TF-CAS comparison. TCAR was associated with significantly lower pooled 30-day risks of stroke (RR, 0.60; 95% CI, 0.48-0.73; I²=0%), death (RR, 0.55; 95% CI, 0.38-0.81; I²=20%), and stroke or death (RR, 0.60; 95% CI, 0.52-0.70; I²=6%), while no significant difference was observed for 30-day myocardial infarction (RR, 0.91; 95% CI, 0.65-1.29; I²=44%). At approximately 1 year, stroke remained comparable between the 2 groups (RR, 0.75; 95% CI, 0.46-1.23; I²=26%), whereas death (RR, 1.09; 95% CI, 1.00-1.20; I²=66%) and stroke or death (RR, 0.79; 95% CI, 0.71-0.87; I²=45%) differed, with the pooled stroke-or-death estimate favoring TCAR. Current observational evidence suggests that TCAR compares favorably with TF-CAS in asymptomatic carotid stenosis. When compared with CEA, TCAR does not appear to provide a clear benefit in pooled perioperative neurologic outcomes, although myocardial infarction may occur less frequently after TCAR.
11 June 2026
Read appraisal →Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation
Association of intensive blood pressure lowering with health-related quality of life after endovascular thrombectomy: a post-hoc analysis of the ENCHANTED2/MT trial
BACKGROUND AND PURPOSE: Intensive blood pressure (BP) targets of less than 120 mm Hg have been shown to worsen functional outcomes after endovascular thrombectomy (EVT) for acute ischemic stroke. However, their effects on self-reported health-related quality of life (HRQoL) remain uncertain. METHODS: This post-hoc exploratory analysis used data from ENCHANTED2/MT, an open-label, blinded-endpoint randomized trial conducted in 44 Chinese hospitals. Adults with elevated BP within 3 h after successful reperfusion were randomized to intensive (< 120 mmHg) or less intensive (140-180 mmHg) systolic BP targets. HRQoL at 90 days was assessed using the EQ-5D-3 L and EQ visual analogue scale (EQ VAS). Functional outcome was measured by the modified Rankin Scale (mRS). Treatment effects were estimated using adjusted regression models, and causal mediation analysis was performed to explore indirect and direct pathways. RESULTS: Of 816 randomized patients, EQ-5D data were available in 685. At 90 days, both EQ-5D index (0.66 vs. 0.72) and EQ VAS (73.01 vs. 76.84) were lower in the more intensive BP group. Adjusted mean differences favored the less intensive treatment group: 0.06 (95% CI, 0.01 ~ 0.11; P = 0.017) for EQ-5D index and 3.49 (95% CI, 0.38 ~ 6.60; P = 0.028) for EQ VAS. Mediation analysis showed that the association of intensive BP lowering with worse HRQoL was mainly indirect via worse mRS outcomes. CONCLUSIONS: Intensive BP lowering after EVT was associated with modestly worse HRQoL at 90 days. The observed differences were small in magnitude, particularly for EQ VAS relative to commonly reported thresholds for clinical importance. These findings are consistent with less intensive BP targets after EVT and highlight the importance of incorporating patient-reported outcomes in acute stroke trials. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04140110 the Registration Date, 22/10/2019.
7 June 2026
Read appraisal →Neurology
Associations of Baseline Clinical Phenotypes With White Matter Hyperintensity Volume Change: A Study of 4,329 UK Biobank Participants
BACKGROUND AND OBJECTIVES: White matter hyperintensities (WMHs) relate to cognitive and physical impairment. Although WMHs typically progress over time, regression has also been observed. Our aim was to explore baseline clinical phenotypes associated with subsequent WMH volume change in the UK Biobank (UKB). METHODS: We included participants with total volume of WMHs at first and follow-up brain MRI. We assessed 107 preselected clinical phenotypes measured at baseline and preprocessed using the Phenome Scan Analysis Tool (PHESANT). We derived a measure of WMH change as the residual from a linear regression of follow-up WMH volumes on baseline WMH volumes to account for baseline WMH burden. We ran (1) linear regressions for continuous WMH change as the outcome and (2) multinomial logistic regressions comparing progression, regression, and stable groups after categorizing WMH volume change using an established percentile-based approach. Models were unadjusted, partially adjusted (age, sex, total brain tissue volume, follow-up time), or fully adjusted (further adding blood pressure; BP). We corrected p values using false discovery rate (FDR) correction. RESULTS: We included 4,329 participants (median age 52; interquartile range 12), 54.6% female, with a median follow-up of 2.3 years (range 1-7 years). Across follow-up, total brain volume decreased (mean decrease 16,058 mm3) and WMH volume increased (median increase 293 mm3; both p < 0.001). WMHs progressed in 53.9% of participants, regressed in 26.01%, and remained stable in 20%. In fully adjusted linear models, higher diastolic BP was the only baseline phenotype associated with greater WMH progression (0.10 SD higher WMH change per 1 SD higher inverse-rank normal transformed diastolic BP; 95% CI 0.05-0.15, FDR p < 0.05). In multinomial models, hip pain lasting more than 3 months (odds ratio [OR] 0.25, 95% CI 0.11-0.58) and faster walking pace (OR 0.79, 95% CI 0.66-0.95) were inversely associated with WMH progression, whereas hip pain was also inversely associated with WMH regression vs stability (OR 0.31, 95% CI 0.12-0.79; all FDR p < 0.05). DISCUSSION: We established vascular risk factors associated with subsequent WMH volume change in the studied cohort. Distinct clinical and demographic profiles characterized WMH progression, regression, and stable groups. Results suggest that vascular factors relate to WMH change but are sensitive to covariate control. Further studies should establish factors differentially and causally related to WMH progression, regression, and stability.
1 June 2026
Read appraisal →Behavioural brain research
Efficacy of repetitive transcranial magnetic stimulation at different frequencies for post-stroke cognitive impairment: A network meta-analysis
PURPOSE: Post-stroke cognitive impairment (PSCI) affects nearly half of stroke survivors, necessitating effective interventions. This Bayesian network meta-analysis evaluated the efficacy of various repetitive transcranial magnetic stimulation (rTMS) protocols for PSCI. METHODS: We systematically searched PubMed, Cochrane Library, and Chinese databases up to December, 2025, including 37 randomized controlled trials (2543 patients) comparing rTMS protocols with different frequencies (low/high) and sites (left/right). Outcomes were measured using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Modified Barthel Index (MBI). RESULTS: Results indicated that high-frequency left dorsolateral prefrontal cortex stimulation (HFL-rTMS) most effectively improved MoCA scores (MD=3.38, SUCRA=87.6%), high-frequency right-sided stimulation (HFR-rTMS) ranked highest for MMSE improvement (MD=2.93, SUCRA=79.7%), and high-frequency bilateral stimulation (HFB-rTMS) yielded the greatest MBI enhancement (MD=13.47, SUCRA=89.6%). CONCLUSIONS: High-frequency rTMS demonstrated superior efficacy in cognitive and functional recovery. HFL-rTMS, HFR-rTMS, and HFB-rTMS are recommended as optimal interventions for MoCA, MMSE, and MBI outcomes, respectively. Further studies are warranted to validate stimulation parameters and expand multicenter evidence for clinical application.
30 May 2026
Read appraisal →JMIR cardio
Barriers and Facilitators to Maintaining Physical Activity After an mHealth Intervention for People Poststroke or Transient Ischemic Attack: Reflexive Thematic Analysis
BACKGROUND: Regular physical activity is critical for preventing secondary stroke following a stroke or transient ischemic attack (TIA). Although mobile health (mHealth) interventions have shown promise for promoting short-term increases in physical activity, evidence on their long-term effects and the mechanisms that support sustained behavior change remains limited. In particular, little is known about how people poststroke or TIA integrate the skills, knowledge, and habits gained through mHealth interventions into their daily lives once structured intervention support ends. OBJECTIVE: This study aimed to explore the perceived barriers and facilitators of maintaining physical activity among individuals poststroke or TIA after completing an mHealth intervention. METHODS: A qualitative approach was used, involving a strategic sample of 12 participants recruited after they had completed a 6-month mHealth intervention for people poststroke or TIA. The intervention included supervised physical therapy with mHealth support for physical exercises and behavior change (eg, counseling, goal-setting, and self-monitoring), followed by a 6-month postintervention period with access to self-managed mHealth support. To enable richness and depth in participants' accounts, the dataset consisted of 2 semistructured interviews conducted 3 months and 6 months after completing the intervention, along with participant-generated photographs. Between the interviews, participants took photos to reflect their experiences of maintaining physical activity after the intervention. These images served as prompts for dialog and reflection during the second interview. Data were analyzed using reflexive thematic analysis. RESULTS: We generated 3 themes: building experience and knowledge to maintain physical activity, staying physically active in a complex life situation, and the meaning of context for maintaining physical activity after the intervention. Barriers and facilitators were conceptually integrated into a comprehensive understanding of maintaining physical activity, symbolized by the metaphor of a soap bubble, which requires persistence and a supportive environment to stay afloat. The complexity of participants' health and life situations created barriers to maintaining physical activity. To overcome these barriers, developing personal strategies within a supportive social and physical context was crucial. This development was facilitated by the mHealth intervention, which enabled knowledge acquisition of the principles of physical activity after stroke or TIA, along with increased awareness of its health benefits. CONCLUSIONS: mHealth interventions for people poststroke and TIA can serve as a catalyst for physical activity engagement and an enhancer of the knowledge and experience necessary to maintain physical activity after the intervention. Despite health-related and contextual barriers, participants may use personalized strategies, supported by their social and environmental context, to navigate these challenges. These insights highlight opportunities for future mHealth interventions to strengthen the interaction between individuals and their environment and empower tailored strategies for behavior change and long-term physical activity maintenance.
30 May 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Exercise effects on cognitive function and molecular markers in post-stroke patients with cognitive impairment: a systematic review and meta-analysis
INTRODUCTION: Exercise may improve cognitive function in stroke survivors. However, no study has yet examined the most effective exercise modalities and associated changes in biomarkers. This study aims to investigate the effects of different exercise types on cognitive function and biomarker trends, providing evidence-based guidance for early rehabilitation interventions. METHODS: Data from randomized controlled trials were collected from January 1, 2000, to March 6, 2025, using medical subject headings combined with free-text terms from PubMed, Cochrane Library, Embase, Wanfang, CNKI, CSTJ, and the China Medical Information Database. The Cochrane Risk of Bias Tool was used to assess the quality of the studies. Review Manager version 5.4.1 was employed to conduct all statistical syntheses. RESULTS: The forty-four original studies involving 4,450 patients with PSCI(Post-stroke cognitive impairment) were analyzed. Subgroup analysis by exercise intervention type revealed larger effect sizes when combining aerobic exercise with other task-based interventions(cognitive-motor dual-tasking and functional motor training) [SMD = 1.18, 95% CI (0.68, 1.68)]. Patients also showed improvements in motor function [MD = 13.98, 95% CI (10.06, 17.89)] and activities of daily living [MD = 16.78, 95% CI (12.97, 20.58)]. Concerning molecular biomarkers, serum levels of brain-derived neurotrophic factor (BDNF), glutathione (GSH), and neuron-specific enolase (NSE) increased significantly, whereas interleukin-6 (IL-6) levels decreased notably in PSCI patients following exercise therapy. CONCLUSION: Structured exercise effectively improves cognitive recovery, motor skills, and daily functioning in patients with PSCI. These clinical gains are accompanied by favorable peripheral biomarker modulations, characterized by significantly increased serum BDNF and GSH, as well as markedly decreased IL-6 levels.
28 May 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
How can social cognition be improved in neurological patients? a systematic review.
BACKGROUND: The neural network underlying social cognition (SC) may be vulnerable to different types of lesions, but also amenable to recovery through interventions that stimulate brain plasticity. This review assessed current non-pharmacological interventions (NPIs) and their effects on SC in neurological patients. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Randomized controlled studies, cohort studies, cross-sectional studies, case series, case reports, and literature reviews were included if they reported a precise description of the NPI in subjects older than 6 years, with brain or cerebellar lesion. RESULTS: Among 5.077 screened articles, 17 fulfilled the eligibility criteria. These articles provided 19 face-to-face, online or hybrid methods, involving 344 patients with multiple sclerosis, stroke, Parkinson disease, cerebellar ataxia, traumatic brain injuries or mixed acquired brain injuries. The methods were applied in observational and randomized study designs using group or individual settings, involving SC, general cognition, and relational aspects. These NPIs, classifiable into training, rehabilitation or combined interventions, improved SC in patients with various diagnosis and age. CONCLUSIONS: Results show that NPIs for SC in neurological patients is being addressed with insightful methods and study designs with improvement possibility in children and adults suffering different pathologies. This is not sufficient for thorough consensus but can trigger a range of broader high-quality and interdisciplinary clinical and research applications.
27 May 2026
Read appraisal →Lancet (London, England)
Endovascular thrombectomy for patients with large-core ischaemic stroke presenting up to 24 h after onset (ATLAS): a systematic review and individual patient data meta-analysis with central imaging adjudication
BACKGROUND: Patients with extensive ischaemic change are often excluded from endovascular thrombectomy. We aimed to synthesise the evidence from recent trials in these patients by performing a systematic review and individual patient data meta-analysis to estimate treatment benefit, including within clinical and imaging subgroups. METHODS: In this systematic review and meta-analysis, we searched PubMed and Embase for randomised trials published between March 1, 2018, and March 1, 2025, that evaluated efficacy and safety of endovascular thrombectomy compared with medical management in patients with large-core ischaemic stroke (based on an Alberta Stroke Program Early CT Score [ASPECTS] of ≤5 or estimated ischaemic core ≥50 mL) presenting within 24 h of onset. Individual patient-level data from all eligible trials were obtained. A central imaging core laboratory readjudicated ASPECTS and reanalysed ischaemic core volume. A two-stage meta-analysis with random-effects model was used to evaluate the distribution of 90-day modified Rankin Scale (mRS) scores (the primary outcome) using adjusted pooled generalised odds ratios (aGenORs). Missing data were handled by multiple imputation. Safety outcomes were all-cause mortality within 90-day follow-up and neurological worsening within 24-48 h of randomisation, reported as adjusted pooled relative risk (aRR); and symptomatic intracerebral haemorrhage within 36 h of randomisation (reported as risk difference). Subgroup analyses based on clinical and imaging characteristics were done, including subgroups defined by ischaemic core volume, ASPECTS, and time window from onset to randomisation. The meta-analysis was registered with PROSPERO (CRD420251058584). FINDINGS: We included 1886 patients (944 assigned to endovascular thrombectomy and 942 assigned to medical management) from six trials. Baseline characteristics were similar between treatment groups. At day 90, the distribution of mRS scores was improved in patients in the endovascular thrombectomy group (median score 4 [IQR 3-6]; n=940) versus those in the medical management group (5 [4-6]; n=931; aGenOR 1·63 [95% CI 1·42-1·88], p<0·0001). The endovascular thrombectomy group also had reduced mortality (292 [31·1%]) compared with the medical management group (347 [37·3%]; aRR 0·82 [95% CI 0·70-0·97], p=0·022). No significant differences were observed in symptomatic intracranial haemorrhage (ten [1·1%] of 944 vs nine [1·0%] of 942 patients; pooled unadjusted risk difference -0·17 percentage points [95% CI -1·01 to 0·67], p=0·69) or neurological worsening (197 [22·0%] of 896 patients vs 161 [17·9%] of 899; aRR 1·19 [0·87-1·62], p=0·27). Improved functional outcomes with endovascular thrombectomy were consistent across clinical and imaging subgroups, except for those with an estimated ischaemic core volume of 150 mL or greater, in whom point estimates favoured endovascular thrombectomy, particularly in the early time window (0-6 h), but wide 95% CIs limited interpretation. INTERPRETATION: Endovascular thrombectomy was associated with improved functional outcomes and reduced mortality versus medical management in patients with large-core ischaemic stroke presenting within 24 h of onset. With the exception of very extensive ischaemic changes (core volume ≥150 mL) presenting beyond 6 h, where evidence remains limited, benefit was sustained across ASPECTS and ischaemic core strata for patients presenting up to 24 h after onset. FUNDING: None.
24 May 2026
Read appraisal →Studies in health technology and informatics
Machine Learning Applications Within the Earlier Medicine Framework for Stroke: A Scoping Review
This scoping review explores how machine learning (ML) has been applied to stroke research within the Earlier Medicine framework, which promotes proactive and personalized care through primary (preventive care), secondary (acute care), and tertiary (chronic care) prevention levels. Following PRISMA-ScR guidelines, studies were identified from PubMed and Scopus, yielding 105 eligible studies. Most studies focused on tertiary prevention, such as predicting in-hospital mortality, complications, and functional outcomes, while fewer addressed early risk prediction or acute-phase detection. Common predictors included age, NIHSS score, glucose, stroke volume, BMI, hypertension, and diabetes, reflecting reliance on routine clinical data. Traditional ML models (e.g., logistic regression, random forest, SVM) remain dominant, although Ensemble/Hybrid and Deep Learning models have increased steadily since 2021. ML demonstrated promising predictive accuracy and clinical potential, though challenges remain in data heterogeneity, model transparency, and external validation.
24 May 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Prediction and diagnosis of post-stroke epilepsy using artificial intelligence approaches: a systematic review and meta-analysis
INTRODUCTION: Post-stroke epilepsy (PSE) is a common complication following a stroke and is a major cause of epilepsy in the elderly. Artificial intelligence (AI) is currently developing rapidly in the medical field and has a promising outlook in disease diagnosis, treatment, and prognosis. METHODS: We screened five studies that fully met the requirements from the PubMed, Web of Science, and EMBASE databases using relevant search terms such as PSE and AI, and analyzed the role of AI in predicting and diagnosing PSE in these studies. RESULTS: The results showed that the sensitivity of AI in predicting and diagnosing PSE was 88% (95% CI 0.78-0.94), and the specificity was 83% (95% CI 0.79-0.86). The area under the summary receiver operating characteristic (SROC) curve was 0.90 (95% CI 0.87-0.92). CONCLUSION: These results indicate that using AI to predict and assist in diagnosing PSE demonstrates high specificity and sensitivity, and has certain prospects in the future auxiliary diagnosis of PSE.
23 May 2026
Read appraisal →Journal of neurology
Effectiveness of telemedicine-based rehabilitation after stroke: a systematic review
BACKGROUND: Access to timely post-acute stroke rehabilitation remains inconsistent, contributing to persistent disability despite advances in acute stroke care. Telemedicine has been proposed as a strategy to improve continuity and access to rehabilitation services, but its effectiveness across functional domains remains incompletely defined. OBJECTIVE: To evaluate the effectiveness of telemedicine-delivered post-acute follow-up and rehabilitation on functional recovery and disability outcomes among adult stroke survivors. METHODS: A systematic review was conducted in accordance with PRISMA guidelines. PubMed, Embase, Scopus, and Web of Science were searched for studies published between January 2015 and December 2025. Eligible studies included adult stroke populations receiving telemedicine-based post-acute follow-up or rehabilitation and reporting functional, motor, balance, quality-of-life, or feasibility outcomes. Randomized controlled trials and observational studies were included. Risk of bias was assessed using validated tools, and findings were synthesized narratively without quantitative pooling due to heterogeneity. RESULTS: Twenty-eight studies comprising approximately 1237 participants were included. Telerehabilitation was associated with improvements in activities of daily living, although between-group differences varied across studies. Activities of daily living improved post-discharge (Barthel Index + 23.3 vs + 9.3; p < 0.001), and Functional Independence Measure scores increased in tele-CIMT and wearable-assisted interventions. Upper limb performance improved (WMFT time - 2.28 s; Box and Block Test + 5.57 vs 1.0; Nine-Hole Peg Test - 71.6 s; Jebsen-Taylor - 26.6 s). Spasticity decreased (MAS) with wrist improvements maintained at 6 months. Mobility and balance also improved, with intervention groups walking farther (6MWT 141.6 ± 8.7 m vs 129.5 ± 7.1 m; p < 0.001) and showing comparable improvements in BBS outcomes across groups. Technology-assisted telerehabilitation programs were more frequently associated with statistically significant improvements; however, these findings were not consistently superior to standard rehabilitation across all studies. Most randomized trials had some concerns for bias, and half of non-randomized studies were rated as serious risk, limiting overall certainty. CONCLUSIONS: Telemedicine-based post-acute stroke rehabilitation is feasible and associated with functional improvements comparable to in-person care. Reported adverse events were infrequent and generally minor, though safety outcomes were inconsistently measured across studies. High feasibility, adherence, and patient satisfaction support its role as a scalable component of post-stroke rehabilitation pathways.
23 May 2026
Read appraisal →Lasers in medical science
Functional and ultrasonographic evaluation of high intensity laser therapy and Kinesio taping in stroke patients with hemiplegic shoulder pain: a randomized controlled trial
Hemiplegic shoulder pain (HSP) is a common post-stroke complication that limits functional recovery and rehabilitation participation. The objective of this study was to evaluate and compare the clinical, functional, and ultrasonographic superiority of High-Intensity Laser Therapy (HILT) and Kinesio Taping (KT) over each other, as well as in comparison to conventional therapy (COT). The study was designed as a prospective, double-blind, randomized controlled trial. Participants were allocated into three equal groups (n = 11 each group): Group 1 (Control Group) received COT with sham HILT and sham KT, Group 2 (HILT Group) received COT with active HILT and sham KT, and Group 3 (KT Group) received COT with sham HILT and active KT. COT was performed five days per week for three weeks, HILT was administered in 10 sessions, and KT was applied every other day for three weeks (nine sessions). The primary outcome measure of the study was the Shoulder Pain and Disability Index (SPADI) score. Secondary outcome measures included pain intensity assessed using the Visual Analog Scale (VAS), passive shoulder range of motion (pROM), ultrasonographic findings, Brunnstrom Recovery Stage (BRS), the Functional Independence Measure (FIM), and the Health Assessment Questionnaire (HAQ). All measures were evaluated at baseline (pre-treatment) and immediately following the intervention period (post-treatment). Data were analyzed using repeated measures ANOVA and McNemar tests. Groups were sociodemographically comparable (p > 0.05). Post-treatment, all groups exhibited significant improvements in shoulder flexion, extension, external rotation, and BRS, VAS, SPADI, FIM, and HAQ scores (p < 0.05). No significant changes occurred in ultrasonographic findings, shoulder abduction, or internal rotation. Notably, HILT demonstrated superior VAS and SPADI improvements compared to other groups (p < 0.05). HILT provides rapid, clinically significant pain relief and functional recovery in HSP without adverse effects, offering a safe and superior therapeutic option.
23 May 2026
Read appraisal →European heart journal
Surgical left atrial appendage occlusion in valvular heart disease without atrial fibrillation: the OPINION trial
BACKGROUND AND AIMS: While surgical left atrial appendage occlusion (SLAAO) reduces stroke in atrial fibrillation (AF) patients, its efficacy in patients without pre-operative AF but with CHA₂DS₂-VASc ≥2 remains uncertain despite their high post-operative AF risk (15-54%). The aim of this study was to evaluate whether prophylactic SLAAO reduces post-operative thrombo-embolic events in valvular surgery patients. METHODS: The OPINION was a multicentre, open-label, randomized, superiority trial conducted at three cardiac surgery centres in China. Eligible non-AF patients with CHA₂DS₂-VASc ≥2 and an indication for valve repair or replacement due to mitral or aortic valve lesions were randomly assigned (1:1) to undergo SLAAO (intervention arm) or not undergo SLAAO (control arm) during surgery. The primary outcome was a composite of ischaemic stroke, transient ischaemic attack (TIA), or cardiovascular mortality assessed at 1 year. The primary analysis was done in the intention-to-treat population. RESULTS: Between April 2021 and June 2024, a total of 2157 patients were enrolled and randomized. After exclusion of 39 patients who withdrew informed consent, 2118 participants were included in the intention-to-treat population (1062 in the SLAAO group and 1056 in the control group). Baseline characteristics were well-balanced between the SLAAO group and control group (mean age 55.5 [11.4] vs 55.6 [11.5] years, P = .65; female 32.9% vs 32.3%, P = .78; CHA2DS2-VASc score 2.88 [0.98] vs 2.87 [0.96], P = .83; median EuroSCORE II 1.58% [1.42%] vs 1.56% [1.28%], P = .74). The 1-year primary endpoint occurred in 73 (6.9%) patients in the SLAAO group and in 87 (8.2%) patients in the control group (hazard ratio 0.83; 95% confidence interval 0.61-1.14; P = .25). CONCLUSIONS: For valvular surgery patients with CHA₂DS₂-VASc scores ≥2 but no pre-operative AF, routine prophylactic left atrial appendage closure did not significantly reduce the incidence of the primary composite endpoint (ischaemic stroke, TIA, and cardiovascular mortality) at 1-year follow-up. TRIAL REGISTRATION: ChiCTR.org registry ChiCTR2100042238.
22 May 2026
Read appraisal →BMJ open
Measurement of quality of stroke care with national electronic health records: a prospective cohort study during and after the COVID-19 pandemic
OBJECTIVES: To evaluate the value of linked electronic health records (EHRs) for measuring stroke care quality in England before and after the COVID-19 pandemic, focusing on metrics not routinely captured: stroke incidence, dispensing of secondary prevention medications and a proxy of disability-time spent at home after stroke ('home-time'). DESIGN: Prospective cohort study using national linked datasets. SETTING: England-wide health data linkage including the Sentinel Stroke National Audit Programme (SSNAP), primary and secondary care, dispensed medications and mortality records, accessed via National Health Service (NHS) England's Secure Data Environment. PARTICIPANTS: 425 675 adults with a first stroke between 1 January 2020 and 31 December 2023; data were available for 304 210 in primary care, 279 825 in hospital admissions, 220 470 in SSNAP and 59 465 in death records. MAIN OUTCOME MEASURES: Annual stroke incidence; first-year medication dispensing rates for antiplatelets, anticoagulants, antihypertensives and lipid-lowering agents (with a 1-month washout period) and home-time at 180 days post stroke. RESULTS: Stroke ascertainment was highest when combining all sources, with 10.8% of non-fatal ischaemic strokes recorded exclusively in primary care and 19.4% of fatal strokes identified solely through death records. Standardised annual stroke incidence rose from 227.6 (95% CI 226.1 to 229.0) to 244.8 (95% CI 243.4 to 246.3) per 100 000 over the study period including the COVID-19 pandemic. During the COVID-19 lockdown, non-fatal stroke recordings decreased while stroke-related deaths rose, indicating that recording quality was sensitive to shifts in healthcare-seeking behaviour during the pandemic. Among people with ischaemic stroke, 89.1% received an antiplatelet or anticoagulant, 44.5% an antihypertensive and 80.5% a lipid-lowering therapy. For haemorrhagic stroke, these proportions were: for anticoagulants 13.5%, antiplatelets 13.2%, antihypertensives 46.6% and lipid lowering 41.1%. Medication dispensing for stroke prevention declined with increasing age and comorbidity, but varied little by ethnicity, region or pandemic period. Mean home-time within 180 days of stroke was 166.6 (95% CI 166.4 to 166) days, decreasing with greater age (141.4 days for 90 years or older (95% CI 140.7 to 142.1)), deprivation (166.4 days (95% CI 166.1 to 166.6) for most deprived quintile) and stroke severity (137.4 days for National Institutes of Health Stroke Scale (NIHSS) score on arrival over 22 (95% CI 135.8 to 139.1)) and increasing with years from the COVID-19 pandemic 2023 (169.3 days (95% CI 169.0 to 169.5) vs 2020 164.4 days (95% CI 164.1 to 164.7)). CONCLUSIONS: Standardised stroke incidence increased significantly over the study period, highlighting a growing public health burden that persisted despite disruptions due to the pandemic although variation in case ascertainment and stroke coding practices was observed. While secondary prevention coverage for antiplatelets and lipids was high, lower rates of dispensing of antihypertensives, particularly in older and comorbid populations, potentially signal a target for improvement. Home-time represents a sensitive, person-centred outcome that exposes disparities linked to socioeconomic deprivation and clinical severity that can be used to enhance routine stroke audits. These findings justify the expansion of linked EHR infrastructure and the modernisation of governance frameworks to enable the longitudinal evaluation of care quality beyond the COVID-19 era.
20 May 2026
Read appraisal →Journal of medical Internet research
Efficacy of Digital Speech Therapy for Poststroke Dysarthria: Randomized Noninferiority Trial
BACKGROUND: Poststroke dysarthria, a common speech impairment, affects up to half of all stroke survivors, often reducing their ability to communicate, and adversely affecting their quality of life. Although conventional speech therapy for poststroke dysarthria is effective, access is often limited by time and geographical constraints. Here, digital speech therapy may serve as a remotely deliverable alternative for selected patients. However, few trials have assessed its efficacy, safety, and usability. OBJECTIVE: This study aimed to evaluate whether a smartphone-based speech therapy app is noninferior to conventional workbook-based therapy in improving speech intelligibility among individuals with poststroke dysarthria. METHODS: This single-blind, randomized controlled, noninferiority trial was performed at 3 hospitals in South Korea. Adults (≥19 y) with poststroke dysarthria who were cognitively intact, without aphasia, and able to use a smartphone were eligible. Participants were enrolled between July 20, 2023, and April 15, 2024. Participants were randomly assigned (1:1), stratified by stroke phase, using a block randomization method, to receive either a smartphone-based digital therapy app or a conventional workbook-based therapy for 4 weeks. The primary outcome was speech intelligibility (0-100 perceptual rating) after the intervention. Primary analysis was intention-to-treat using analysis of covariance. A noninferiority margin of 19 points was pre-defined. RESULTS: A total of 73 participants were enrolled (median age 62.00 years). Among them, 38 were assigned to the digital speech therapy group and 35 to the control group. Intelligibility scores improved from 80.48 (SD 18.92) to 92.08 (SD 12.38) in the intervention group, and from 80.94 (SD 16.74) to 88.11 (SD 18.06) in the control group. The adjusted between-group difference was 4.49 (95% CI 0.61-8.37), and the lower bound of the 95% CI was above the prespecified noninferiority margin (-19), which supported noninferiority. No significant between-group differences were observed in the secondary outcomes related to speech function or psychological status. The system usability score was 89.6, and adherence in the digital speech therapy group was 64.6% based on app logs, with no treatment-related adverse events. CONCLUSIONS: Digital speech therapy was noninferior to conventional workbook-based therapy in improving speech intelligibility and was feasible across acute to early subacute and chronic stroke phases in cognitively intact stroke survivors with predominantly mild-to-moderate dysarthria. However, feasibility and efficacy in older stroke survivors with cognitive deficits or co-occurring aphasia, or in those unable to use smartphones, remain to be established.
19 May 2026
Read appraisal →Annals of medicine
Endovascular thrombectomy versus best medical therapy for acute vertebrobasilar artery occlusion in patients with low NIHSS scores: a meta-analysis
OBJECTIVE: The efficacy of endovascular thrombectomy (EVT) for acute vertebrobasilar artery occlusion (VBAO) presenting with mild symptoms (National Institutes of Health Stroke Scale [NIHSS] score ≤10) remains uncertain. This meta-analysis aimed to compare the effectiveness and safety of EVT versus best medical therapy (BMT) in this population. METHODS: We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to September 2025 for comparative studies. The primary outcome was 90-day excellent functional outcome (modified Rankin Scale [mRS] score 0-1). Secondary outcomes included functional independence (mRS 0-2), symptomatic intracranial hemorrhage (sICH), and all-cause mortality. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model. RESULTS: Seven observational studies involving 3,107 patients were included. In unadjusted analyses, EVT was associated with a higher rate of excellent functional outcome (OR 2.17; 95% CI 1.58-2.96) but not with functional independence (OR 1.58; 95% CI 0.90-2.77). After adjustment for confounders, EVT was associated with higher rate of excellent functional outcome (OR 2.86; 95% CI 1.89-4.31) and functional independence (OR 1.91; 95% CI 1.01-3.62). Safety outcomes including sICH and mortality did not differ significantly between groups. CONCLUSION: In patients with acute VBAO and mild symptoms, EVT may be associated with superior functional outcomes compared to BMT alone, without a significant increase in procedural risks. These findings suggest a potential role for EVT in selected patients with low NIHSS scores and underscore the need for confirmation in randomized trials.
18 May 2026
Read appraisal →Journal of neurology
Diagnostic and prognostic value of blood neurofilament light chain in ischemic stroke: an individual patient data meta-analysis
BACKGROUND: We aimed to conduct an individual patient data meta-analysis on blood neurofilament light chain (NfL) in ischemic stroke (IS) to enhance its clinical applicability. METHODS: We performed a systematic literature search of studies on blood NfL measured in adult patients within 30 days after IS onset and derived age- and BMI-adjusted Z-scores based on a previously published reference population of healthy controls. We collected clinical, radiological and biochemical parameters of IS patients and tested associations of NfL at defined timepoints after IS onset (D1: < 24 h; D2: 24-48 h; D3: 48-72 h; D4-5: 72-120 h; D6-7: 120-168 h; D8-30: > 168 h) with baseline characteristics and 3-month follow-up outcomes (modified Rankin Scale, mRS; survival). RESULTS: We included 4081 blood NfL values from 2872 participants (IS n = 1985, transient ischemic attack n = 88, healthy controls n = 799) of 18 published studies and 3 unpublished cohorts. In patients with IS, NfL Z-score progressively increased from D1 [median: 2.0 (IQR: 0.9-2.9)] to D6-7 [median: 3.5 (IQR: 3.0-3.8)], with discriminative ability being high for IS vs. controls (AUC: 0.79-0.97) and fair for IS vs. TIA (AUC: 0.64-0.80). Higher NfL Z-score at D1 was associated with greater risk of symptomatic intracranial hemorrhage (aOR = 1.33, p = 0.014) and, from D2 onwards, with larger infarct lesion volume (highest Spearman's rho: 0.795 at D6-7). NfL independently predicted a mRS > 2 (aOR = 1.31, p < 0.001) and mortality (aOR = 1.67, p < 0.001) at 3 months. CONCLUSIONS: Blood NfL level was progressively elevated after IS, could discriminate IS from healthy controls with high accuracy and had prognostic value for intra-hospital complications and 3-month clinical outcomes in IS.
18 May 2026
Read appraisal →Lancet (London, England)
Ticagrelor with aspirin dual antiplatelet therapy combined with intravenous thrombolysis in patients with ischaemic stroke in China (TAPIS): a multicentre, double-blind, randomised controlled trial
BACKGROUND: Evidence supporting the early addition of antiplatelet therapy to intravenous thrombolysis in patients with acute ischaemic stroke remains inconclusive. We aimed to investigate the efficacy and safety of early oral dual antiplatelet therapy (DAPT), started within 6 h of onset, as an adjunct to intravenous thrombolysis. METHODS: TAPIS was a randomised, double-blind, placebo-controlled trial done in 60 hospitals across China. We enrolled patients treated with intravenous thrombolysis for ischaemic stroke, with a National Institutes of Health Stroke Scale score of 4-10. We randomly assigned (1:1) patients to receive oral aspirin plus ticagrelor (DAPT group) or corresponding placebo within 6 h of stroke onset, either before, during, or after receiving thrombolysis. Ticagrelor or placebo was continued for days 2-7 in each group, with open-label aspirin administered for days 2-90. Patients, clinicians, and investigators were masked to the group assignment. The primary efficacy outcome was an excellent functional outcome (modified Rankin Scale score 0-1) at 90 days. The primary safety outcome was symptomatic intracranial haemorrhage within 36 h. This trial was registered with ClinicalTrials.gov (NCT06316570) and is completed. FINDINGS: Between April 3, 2024, and Sept 30, 2025, we randomly assigned 1382 patients to the early DAPT (n=690 [49·9%]) or placebo (n=692 [50·1%]) groups. The median age was 65·6 years (IQR 58·3-72·0), 991 (71·7%) were men, and 391 (28·3%) were women. At 90 days, 474 (68·7%) patients in the early DAPT group and 429 (62·0%) in the placebo group achieved excellent functional outcomes (risk ratio 1·11 [95% CI 1·03-1·20; p=0·0089). Symptomatic intracranial haemorrhage within 36 h occurred in six (0·9%) patients in the early DAPT group versus five (0·7%) in the control group (risk ratio 1·20 [95% CI 0·37-3·93; p=0.76). INTERPRETATION: Among patients treated with intravenous thrombolysis for moderate ischaemic stroke, initiation of oral DAPT within 6 h of onset improved the likelihood of excellent functional outcomes at 90 days. Although no significant between-group difference in symptomatic intracranial haemorrhage was detected, wide CIs precluded exclusion of a small increased risk. FUNDING: National Natural Science Foundation of China, Capital's Funds for Health Improvement and Research, Noncommunicable Chronic Diseases-National Science and Technology Major Project, Beijing Municipal Science & Technology Commission, and the New Cornerstone Science Foundation.
18 May 2026
Read appraisal →Computer methods and programs in biomedicine
Integrating multimodal data and deep learning for functional assessment and rehabilitation prediction after cerebral hemorrhage
BACKGROUND: Intracerebral hemorrhage (ICH) is a leading cause of long-term disability, particularly in China. Post-stroke motor recovery exhibits considerable heterogeneity, presenting substantial challenges for clinicians in establishing realistic goals. While integrative AI paradigms have shown success in other complex medical domains, existing models often rely on single-modality data, limiting their predictive accuracy and clinical utility. This study aims to develop and validate a multimodal predictive model integrating CT imaging, clinical data, and rehabilitation assessments to simultaneously predict motor recovery and global rehabilitation outcomes following cerebral hemorrhage. METHODS: We conducted a retrospective study involving 739 patients (315 for motor function prediction and 424 for rehabilitation outcome assessment) who received rehabilitation therapy after cerebral hemorrhage. To predict motor function, we constructed a late-fusion deep learning model leveraging 3D-DenseNet for CT neuroimaging and Multi-Layer Perceptron (MLP) for clinical and laboratory features. To predict rehabilitation outcomes, a Gradient Boosting Decision Tree (GBDT) model was developed and validated using 5-fold and 10-fold cross-validation, comparing it against other machine learning algorithms, including SVR, Random Forest and AdaBoost. Model performance was assessed using metrics including AUC and R². Additionally, univariate and multivariate regression analysis were performed to identify significant factors influencing motor recovery and rehabilitation outcomes. RESULTS: A total of 739 patients were included. The multimodal fusion model achieved an AUC of 0.856 (95 % CI: 0.741-0.971) and an F1 score of 0.897 (95 % CI: 0.819-0.975), significantly outperforming the imaging-only (AUC: 0.833) and clinical-only (AUC: 0.749) models. For rehabilitation outcome prediction, the GBDT model achieved an R2 of 0.849 (95 % CI: 0.803-0.887), demonstrating superior stability and accuracy over other models. Additionally, multivariate analysis revealed that serum albumin (ALB), neutrophil percentage (NEUT%), triglycerides (TG), and thrombin time (TT) were independent predictors of motor recovery, while age, admission mBI, and time to start rehabilitation significantly influenced functional outcomes. CONCLUSION: This study confirms that a multimodal deep learning framework integrating routinely available CT imaging and clinical biomarkers provides high predictive value for simultaneously forecasting motor recovery and global functional outcomes after ICH. This proof-of-concept approach offers a reproducible, data-driven tool for early risk stratification, facilitating the formulation of individualized rehabilitation strategies and optimizing resource allocation in clinical workflows.
17 May 2026
Read appraisal →Journal of neurointerventional surgery
Long-term outcomes of the Woven EndoBridge device for intracranial aneurysms: systematic review and meta-analysis
BACKGROUND: The Woven EndoBridge (WEB) device is widely recognized as a safe and effective treatment for intracranial aneurysms (IAs). However, data on the long-term evolution of aneurysm occlusion remain limited. This meta-analysis evaluates the long-term (≥1 year) safety and efficacy outcomes of patients treated with the WEB device. METHODS: A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus for studies published between January 1, 2011 and August 1, 2024 following PRISMA guidelines. Studies reporting outcome for IAs treated with the WEB device and a follow-up period of ≥1 year were included. Data were pooled using a random-effects model to account for variability across studies. RESULTS: A total of 25 studies including 1735 patients and 1768 aneurysms were analyzed (30.1% ruptured). The pooled adequate occlusion rates were 87.3% (95% CI 83.5% to 91.1%) at 1 year, 90.7% (95% CI 86.2% to 95.2%) at 1-2 years, 93.3% (95% CI 87.7% to 99.0%) at 3 years, and 88.4% (95% CI 80.5% to 96.4%) at 5 years. Adequate occlusion was achieved in 89.2% (95% CI 83.0% to 93.2%) of unruptured aneurysms and 85.9% (95% CI 80.2% to 90.1%) of ruptured aneurysms. The overall retreatment rate at the last long-term follow-up was 7.2% (95% CI 4.8% to 9.6%). No procedure- or device-related adverse events were reported beyond 1-year follow-up. Additionally, no cases of delayed rupture or aneurysm rebleeding were observed. CONCLUSION: This systematic review and meta-analysis confirms the high long-term efficacy and safety of the WEB device in treating both ruptured and unruptured aneurysms. The findings support the WEB device as a reliable and effective treatment option for IAs.
16 May 2026
Read appraisal →Journal of neurointerventional surgery
Comparative safety and efficacy of invasive therapies for carotid artery stenosis: a systematic review and network meta-analysis
BACKGROUND: Carotid artery stenosis is a major cause of stroke and is commonly treated with carotid endarterectomy (CEA) or carotid artery stenting (CAS). Trans-carotid artery revascularization (TCAR) has emerged as a newer alternative designed to reduce the risk of procedural stroke. However, comparative evidence on the safety and efficacy of these interventions is limited. This study evaluates the clinical outcomes of CEA, CAS, and TCAR in patients with carotid artery stenosis. METHODS: A comprehensive search of multiple databases was conducted to identify relevant studies. The outcomes were stroke, mortality, and myocardial infarction, cranial nerve injury, hematoma, infection, transient ischemic attack, and length of hospital stay. Meta-analysis and a frequentist graph-theoretical approach network meta-analysis were performed using the netmeta package in R platform. Risk of bias was assessed using RoB 2 Cochrane and ROBINS-I. RESULTS: Fifty-five studies were included in the review. The short-term stroke risk was significantly lower with CEA than with CAS. TCAR had a potential long-term mortality benefit over CAS, while no significant differences were observed in short-term mortality or myocardial infarction across treatments. CAS was associated with lower risks of cranial nerve injury, hematoma, and infection compared with CEA. CONCLUSION: CEA and TCAR offer better short-term stroke protection than CAS, with TCAR showing promise for long-term mortality benefits. CAS has advantages in reducing cranial nerve injury, hematoma, and infection risks. Overall, the choice of treatment should consider both efficacy and safety profiles. Further high-quality randomized controlled trials, particularly focusing on TCAR, are needed to validate these comparative outcomes. PROSPERO REGISTRY NUMBER: CRD420251055287.
16 May 2026
Read appraisal →Journal of neurointerventional surgery
Intravenous tenecteplase is associated with a higher incidence of thrombus movement before endovascular treatment for acute ischemic stroke: a secondary analysis of the AcT randomized controlled trial
BACKGROUND: Thrombus migration can occur in patients receiving IV thrombolysis for acute stroke. This study compared the effects of IV tenecteplase (0.25 mg/kg) versus alteplase (0.9 mg/kg) on thrombus movement in patients undergoing endovascular treatment (EVT) in the AcT trial. METHODS: Patients with intracranial occlusion on baseline CT angiography (CTA) who underwent EVT were included. Thrombus movement from baseline CTA to first angiographic EVT run was classified as no thrombus movement, thrombus extension (TE, movement to a proximal location on DSA compared with CTA), thrombus migration (TM, movement to a more distal location), or recanalization. Outcomes were 90-day modified Rankin Scale (mRS) score 0-2 and final extended Thrombolysis in Cerebral Infarction score 2b-3. Mixed-effects logistic regression was performed. RESULTS: Of the 1577 patients in the AcT trial, 496 patients with intracranial occlusions underwent EVT (median age 73 years, 50.8% female). No thrombus movement was seen in 398 patients (80.2%), TE in six (1.2%), TM in 77 (15.5%), and complete recanalization in 15 (3.0%). Tenecteplase recipients (n=252) had higher TM rates than alteplase recipients (19.4% vs 11.5%, adjusted OR (aOR) 1.83, 95% CI 1.10 to 3.07). TM did not impact final successful reperfusion (aOR 0.76, 95% CI 0.40 to 1.38) but was associated with increased odds of 90-day mRS 0-2 (aOR 1.77, 95% CI 1.05 to 3.06). Thrombolytic type did not affect the relationship between thrombus movement and study outcomes (P>0.05). CONCLUSION: IV tenecteplase is associated with higher thrombus migration rates before EVT compared with alteplase, which is linked to better functional outcomes. However, the type of thrombolytic agent did not affect final reperfusion and functional outcomes.
16 May 2026
Read appraisal →The New England journal of medicine
Endovascular Treatment of Medium-Vessel-Occlusion Strokes
BACKGROUND: Endovascular thrombectomy for acute ischemic stroke due to medium-vessel occlusion has had varying results across trials. Whether thrombectomy improves functional outcomes in patients with medium-vessel occlusion and moderate-to-severe deficits is unclear. METHODS: We conducted an open-label, randomized trial with blinded outcome assessment at 48 centers in China. Eligible patients were adults who presented within 24 hours after the onset of a moderate-to-severe stroke (National Institutes of Health Stroke Scale [NIHSS] score, ≥6; scale, 0 to 42, with higher scores indicating greater neurologic deficits) due to occlusion of a medium vessel. Patients were assigned in a 1:1 ratio to thrombectomy plus medical management (thrombectomy group) or medical management alone (control group). The primary outcome was functional disability as measured by the shift in the modified Rankin scale score (scale, 0 [no disability] to 6 [death]) at 90 days. Violation of the proportional-odds assumption precluded the use of shift in the modified Rankin scale score, so as prespecified, functional independence (modified Rankin scale score of 0, 1, or 2) at 90 days was used as the primary outcome. Safety outcomes were symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: Among 280 patients in the thrombectomy group and 283 in the control group, the median age was 71 years, the median NIHSS score was 10 (range, 3 to 36), and 42.8% were women; 36.6% received intravenous thrombolysis. Functional independence at 90 days was seen in 58.6% of the patients in the thrombectomy group and in 46.6% of those in the control group (adjusted rate ratio, 1.24; 95% confidence interval, 1.07 to 1.44; P = 0.004). The incidence of symptomatic intracranial hemorrhage was 4.7% in the thrombectomy group and 2.2% in the control group; 90-day mortality was 11.1% and 10.2%, respectively. CONCLUSIONS: Among patients with acute ischemic stroke due to medium-vessel occlusion and moderate-to-severe deficits, thrombectomy led to a greater likelihood of functional independence than medical management alone but also to a higher risk of symptomatic intracranial hemorrhage. (Funded by the National Natural Science Foundation of China and the Noncommunicable Chronic Diseases-National Science and Technology Major Project; ORIENTAL-MeVO ClinicalTrials.gov number, NCT06146790.).
15 May 2026
Read appraisal →Journal of molecular neuroscience : MN
Development and Validation of a SHAP-Interpretable Machine Learning Model for Stroke Risk Prediction Using Circulating MicroRNA Biomarkers
BACKGROUND/OBJECTIVE: Stroke remains a leading cause of morbidity and mortality worldwide. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for cardiovascular disease diagnosis and risk stratification. However, their integration into predictive models remains limited by challenges in feature selection, model robustness, and interpretability. This study aims to develop an interpretable machine learning framework for predicting stroke incidence using serum miRNA signatures. METHODS: We analyzed serum miRNA expression profiles from 1,785 human samples (173 stroke patients and 1,612 non-stroke controls) obtained from the GEO dataset GSE117064. Differential expression analysis was performed to identify significantly dysregulated miRNAs using linear modeling and empirical Bayes moderation. LASSO logistic regression was then applied to select predictive miRNA features. Five supervised machine learning classifiers-logistic regression, support vector machine (SVM), random forest, XGBoost, and k-nearest neighbors-were evaluated using 10-fold cross-validation. The best-performing model (SVM) was further interpreted using Shapley Additive exPlanations (SHAP) to assess individual miRNA contributions to prediction. To validate the robustness and clinical generalizability of the identified signatures, quantitative real-time PCR (qPCR) and Next-Generation Sequencing (NGS) were performed on independent sets of serum samples. The pre-trained SVM model was applied to the NGS data to verify its classification performance in an external cohort. RESULTS: A total of 604 miRNAs were differentially expressed between stroke and non-stroke groups, including 206 downregulated and 398 upregulated candidates. LASSO regression identified 66 non-zero-coefficient miRNAs with potential predictive value. Among the classifiers tested, the SVM model achieved the highest average accuracy of 0.9983 and perfect AUC (1.0000), demonstrating superior performance and stability. SHAP analysis revealed that a subset of miRNAs, including hsa-miR-3648, hsa-miR-1290, and hsa-miR-6765-3p, had the greatest impact on classification outcomes, providing mechanistic insights and enhancing model interpretability. qPCR results preliminarily supported the differential expression patterns of key miRNAs. Furthermore, NGS analysis of an independent validation cohort (n = 10) demonstrated distinct hierarchical clustering of the selected biomarkers. The pre-trained SVM model preliminarily supported its cross-platform validity by classifying these external samples with an overall accuracy of 80% (sensitivity 80%, specificity 80%), suggesting the potential generalizability of the identified miRNA panel across different quantification platforms. CONCLUSIONS: This study demonstrates the utility of integrating differential expression analysis, regularized feature selection, and machine learning with SHAP-based interpretation to identify and validate serum miRNA signatures predictive of stroke. The successful external validation using NGS highlights the robustness of the identified biomarkers and their potential for cross-platform application. The results provide a transparent, data-driven framework for biomarker discovery in clinical risk prediction and support the development of non-invasive diagnostic tools for stroke detection.
14 May 2026
Read appraisal →PloS one
Effects of deconstructed Tai Chi step training combined with conventional rehabilitation on lower limb function in brunnstrom stage III stroke patients: A randomized controlled trial
OBJECTIVE: To evaluate whether a deconstructed Tai Chi stepping protocol adapted for patients with Brunnstrom Stage III stroke, when combined with conventional rehabilitation, improves lower limb motor function, walking ability, and joint mobility compared with conventional rehabilitation plus limb synergy training. METHODS: In this assessor-blinded randomized controlled trial, 52 patients with subacute stroke (Brunnstrom Stage III, ≤ 6 months post-stroke) were randomized in a 1:1 ratio to an experimental group (conventional rehabilitation plus adapted Tai Chi stepping training) or a control group (conventional rehabilitation plus limb synergy training). Both interventions were delivered 5 days per week for 8 weeks. Fifty participants completed the study and were included in the final per-protocol analysis (25 per group). Outcomes were assessed at baseline and after intervention. The primary outcomes were the Fugl-Meyer Assessment for Lower Extremity (FMA-LE) and Holden Walking Function Classification. Secondary outcomes were hip, knee, and ankle range of motion (ROM). RESULTS: Both groups improved after treatment, with greater improvement observed in the experimental group. FMA-LE scores increased by 5.6 ± 1.5 points in the experimental group and 1.8 ± 0.8 points in the control group (p < 0.001, Cohen's d = 1.32). In addition, 92% (23/25) of participants in the experimental group achieved Holden Grades II-III compared with 60% (15/25) in the control group (p < 0.001). The experimental group also showed larger gains in joint ROM, including hip flexion (+19.9° vs. + 4.2°), knee external rotation (+9.9° vs. + 3.7°), and ankle dorsiflexion (+7.6° vs. + 1.3°) (all p < 0.001). CONCLUSION: Deconstructed Tai Chi stepping training combined with conventional rehabilitation was associated with greater improvement in lower limb motor function, walking ability, and joint mobility than conventional rehabilitation plus limb synergy training in patients with Brunnstrom Stage III stroke. This stage-specific protocol may represent a practical adjunct to stroke rehabilitation, although confirmation in larger trials is still needed. CLINICAL TRIAL REGISTRATION: International Traditional Medicine Clinical Trial Registry (ITMCTR; a WHO ICTRP Primary Registry), registration number ITMCTR2025000972.
12 May 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Thrombolysis in spinal cord infarction: Case report and systematic review
INTRODUCTION: Spinal cord infarction (SCI) is a rare but severe cause of acute myelopathy, and evidence supporting reperfusion therapies remains limited. METHODS: We report a 73-year-old man with spontaneous cervical SCI treated with intravenous alteplase and perform a systematic review (database search from inception to 13 November 2025) of case reports/series describing intravenous (IV) or intra-arterial (IA) thrombolysis for SCI, extracting data about clinical presentation, diagnostic and therapeutic work-up and functional outcomes. RESULTS: Our patient improved after thrombolysis and achieved functional independence at 3 months (modified Rankin Scale [mRS] 2). The review identified 21 studies (19 case reports, 2 case series) totaling 25 patients; including our case, 26 patients were analyzed. Mean age was 57.4 years (range 14-83), and anterior spinal artery (ASA) syndrome was the most common presentation. Most patients received IV thrombolysis; 4 underwent IA therapy (alone or combined). Considering the last available assessment, 14/25 patients (56.0%) had a favorable outcome (mRS 0-2), 8/25 (32.0%) had mRS 3, and 3/25 (12.0%) had mRS 4-5. No symptomatic treatment-related hemorrhagic complications were reported. DISCUSSION AND CONCLUSION: Published experience suggests that thrombolysis in carefully selected patients with suspected SCI may represent a reasonably safe therapeutic option, but evidence is limited and subject to major bias. Prospective registries and multicenter studies are needed to clarify safety, efficacy, and selection criteria.
12 May 2026
Read appraisal →AJNR. American journal of neuroradiology
Predicting Intracranial Aneurysm Rupture Risk and Intervention Outcomes Using Denoising-Enhanced CTA
BACKGROUND AND PURPOSE: Our aim was to develop a comprehensive multimodal framework for assessing the rupture risk of intracranial aneurysms and predicting intervention outcomes. In addition, it seeks to a novel denoising algorithm to enhance the quality of CTA images, thereby improving morphologic profiling. MATERIALS AND METHODS: This retrospective multicenter study included 352 patients with intracranial aneurysms who underwent CTA. A multimodal framework was developed, integrating 3 complementary feature sets: clinical variables, radiomic texture features, and deep learning-derived aneurysm morphologic data. A novel denoising algorithm was applied to improve image quality, thereby enhancing prediction performance. Model validation was performed through cross-validation, using multiple end points, including the Hunt-Hess, World Federation of Neurosurgical Societies (WFNS), and mRS grading systems. RESULTS: The multimodal framework demonstrated robust performance, achieving an area under the curve (AUC) of 0.896 [0.819-0.973] for aneurysm rupture prediction, outperforming conventional single-technique models (radiomics-based model: 0.752 [0.693-0.809]; deep learning-based model: 0.823 [0.789-0.827]). Incorporating the denoising technique further enhanced performance, with the AUC for rupture prediction increasing to 0.908 [0.836-0.981]. In clinical grading tasks, the model showed strong efficacy, achieving an AUC of 0.907 [0.845-0.968] for Hunt-Hess grading, 0.883 [0.662-0.988] for World Federation of Neurosurgical Societies grading, and 0.926 [0.879-0.973] for mRS. CONCLUSIONS: Our system demonstrates promising performance in predicting aneurysm rupture and clinical grading assessments, indicating its potential for comprehensive aneurysm evaluation. Moreover, the proposed denoising method effectively mitigates noise interference, enhances morphologic edge features, and improves the accuracy of existing models.
11 May 2026
Read appraisal →AJNR. American journal of neuroradiology
Neuroimaging Predictors of Futile Recanalization in Anterior Circulation Stroke: A Systematic Review and Meta-Analysis
BACKGROUND: Mechanical thrombectomy (MT) has transformed the management of large vessel occlusion stroke; however, a considerable proportion of patients fail to achieve functional recovery despite successful recanalization. This futile recanalization underscores the need to better understand imaging biomarkers that may predict poor outcomes after endovascular therapy. PURPOSE: To systematically review and synthesize evidence on neuroimaging biomarkers associated with futile recanalization after MT in acute ischemic stroke. DATA SOURCES: PubMed, Scopus, Web of Science, and EMBASE databases were searched up to March 2025, supplemented by manual reference screening. STUDY SELECTION: Eligible studies enrolled adult patients with anterior-circulation stroke who underwent thrombectomy, reported pretreatment neuroimaging findings, and evaluated functional outcomes despite successful reperfusion. Case reports, reviews, abstracts, and nonhuman studies were excluded. DATA ANALYSIS: Two reviewers independently screened, extracted data, and assessed study quality using the Prediction Model Risk of Bias Assessment Tool. Random-effects meta-analysis was performed where appropriate. Heterogeneity, publication bias, and sensitivity analyses were undertaken. DATA SYNTHESIS: Fifty-one studies were included. Lower ASPECTS scores were strongly associated with futile recanalization (OR = 0.81). Core infarct volume showed inconsistent associations, whereas perfusion and collateral markers, including elevated hypoperfusion intensity ratio, delayed venous outflow, and poor collateral scores, demonstrated strong predictive value. Chronic white-matter injury, leukoaraiosis, and cerebral atrophy were also consistently associated with worse outcomes. LIMITATIONS: Limitations included heterogeneity in imaging protocols and thresholds; predominance of retrospective single-center cohorts; limited direct comparison across imaging modalities; and variable adjustment for confounders. CONCLUSIONS: Neuroimaging biomarkers, particularly ASPECTS, perfusion-derived metrics, collateral status, and markers of chronic small vessel disease, provide important prognostic information for identifying patients at risk of futile recanalization despite successful thrombectomy.
11 May 2026
Read appraisal →Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation
Quality of life after tranexamic acid in subarachnoid hemorrhage: post-hoc analysis of the ULTRA trial
PURPOSE: The ULTRA trial evaluated the impact of ultra-early and short-term tranexamic acid (TXA) treatment in patients with subarachnoid hemorrhage (SAH) and found no clinical benefit at six months. This post-hoc analysis examines whether TXA improves quality of life (QoL) at three and six months. METHODS: The ULTRA trial was a randomized, controlled, multicenter study conducted from July 2013 to July 2019. Patients received either TXA or standard care. This analysis included patients who completed at least one QoL questionnaire. The primary endpoint was QoL, assessed using the EQ-5D-3L questionnaire at three and six months. Linear mixed models adjusted for confounders were used to analyze the association between TXA and QoL. RESULTS: Of the 955 ULTRA patients, approximately 25% died, and 63% completed at least one QoL questionnaire. At three months, the TXA group had a mean EQ-5D index score of 0.75 versus 0.71 in the control group (p = 0.11) and a mean EQ-5D Visual Analogue Scale (VAS) score of 89 versus 86 (p = 0.10). At six months, the mean EQ-5D index score was 0.84 in the TXA group compared to 0.82 in the control group (p = 0.23), and the mean VAS was 92 in the TXA group compared to 89 in the control group (p = 0.13). CONCLUSION: Ultra-early and short-term TXA did not result in a significant improvement in QoL at three or six months in patients with SAH. Given the lack of benefit on both clinical outcome and QoL, routine use of TXA is not recommended. TRIAL REGISTRATION: Netherlands Trial Register: NTR3272. CLINICALTRIALS: gov: NCT02684812.
10 May 2026
Read appraisal →Journal of medical systems
Prognostic Modeling Based on Post-Endovascular Thrombectomy Systolic Blood Pressure Trajectories Using Explainable Artificial Intelligence: A Secondary Analysis of the OPTIMAL-BP Trial
Blood pressure (BP) management following successful reperfusion after endovascular thrombectomy (EVT) is critical in achieving favorable clinical outcomes. Individualized BP management using predictive modeling by machine learning may further improve prediction of functional outcomes. This study was a retrospective analysis of data from the Outcome in Patients Treated with Intra-Arterial Thrombectomy-Optimal Blood Pressure Control (OPTIMAL-BP) trial, a randomized controlled trial comparing between intensive and conventional BP management during the 24 h after successful recanalization by EVT from June 18, 2020, to November 28, 2022. The trial was conducted across 19 centers in South Korea. Machine learning models were developed to predict functional independence (90-day modified Rankin Scale 0 to 2). Model performance was compared between clinical variables only and systolic blood pressure (SBP) metrics in addition to clinical variables. In addition, the Shapley additive explanations (SHAP) analysis was performed to provide model explanation and understand the importance of SBP metrics. A total of 288 patients (61.1% men, median age 75 years [interquartile range, 65-81]) were included. Among the six algorithms, the deep neural network model incorporating SBP metrics performed best on validation, achieving an area under the curve of 0.86 (95% confidence interval, 0.76-0.92) which was significantly better than the model using only clinical variables (area under the curve 0.80 [95% confidence interval, 0.69-0.88], P = .037). Among SBP metrics, SHAP analysis identified time rate of SBP and minimum SBP as important features, with time rate showing greater influence in the intensive group and minimum SBP in the conventional group. Integrating SBP metrics with clinical variables significantly improved machine learning performance in predicting functional outcomes after successful EVT. Explainable artificial intelligence (AI) identified time rate and minimum SBP as key predictors of outcome. Trial Registration Information: ClinicalTrials.gov (NCT04205305; registered December 17, 2019).
9 May 2026
Read appraisal →Circulation
Prognostic Factors for Long-Term Risk of Stroke After Transient Ischemic Attack or Minor Stroke: A Systematic Review and Meta-Analysis
BACKGROUND: Patients with a transient ischemic attack (TIA) or minor stroke have an increased risk of subsequent stroke that persists for at least 10 years. We aimed to identify prognostic factors associated with long-term risk of stroke in this patient group and estimate their population attributable fraction (PAF). METHODS: A systematic review was performed of MEDLINE, Embase, and Web of Science for cohort studies including patients with TIA or minor stroke that evaluated factors for subsequent stroke over a follow-up period of ≥1 year. We pooled hazard ratios adjusted for relevant confounders using random-effect meta-analysis and determined the PAF of factors based on their pooled prevalence and adjusted hazard ratio. We assessed certainty of evidence using the grading of recommendations, assessment, development, and evaluation approach. The study is registered in PROSPERO (CRD42023476551). RESULTS: From 14 732 identified citations, we included 28 cohort studies comprising 86 810 patients with TIA or minor stroke (median age, 69 years [interquartile range, 65-71]; 52%-60% male patients). Factors that had high certainty evidence of association with increased long-term risk of stroke included older age (adjusted hazard ratio, 1.04 per year increase [95% CI, 1.02-1.05]); male sex (1.25, 1.15-1.36; PAF 13.0% [95% CI, 7.8-18.7]); atrial fibrillation (1.34, 1.18-1.52; 3.8% [95% CI, 0.3-9.9]); diabetes (1.52, 1.32-1.75; 7.7%, 3.1-14.1); hypertension (1.60, 1.31-1.94; 19.3%, 8.4-31.6); ischemic heart disease (1.67, 1.28-2.18; 10.7%, 2.8-22.9); history of stroke or TIA before the index event (1.70, 1.43-2.02; 12.0%, 5.2-21.4); smoking (1.29, 1.05-1.60; 11.2%, 1.0-30.7); ABCD2 (age, blood pressure, clinical features, duration of TIA, and presence of diabetes) score of ≥4 (1.59, 1.31-1.94; 18.0%, 2.9-39.9); presence of acute infarct on neuroimaging (1.97, 1.41-2.74; 19.0%, 5.2-38.9), including diffusion-weighted imaging-positive lesions (1.86, 1.02-3.37; 14.0%, 7.0-25.0); minor stroke as index event (1.75, 1.35-2.27 versus TIA; 28.0%, 10.2-47.6); presentation with aphasia or dysarthria (1.45, 1.24-1.69; 19.2%, 0.2-53.1); presentation with paresis (1.45, 1.15-1.84; 22.0%, 3.8-43.4); and etiologic stroke subtypes, including cardioembolism (2.16, 1.53-3.05; 14.6%, 3.1-33.5), large-artery atherosclerosis (2.19, 1.68-2.86; 13.2%, 5.1-25.5), and small-vessel disease (1.69, 1.14-2.49; 16.8%, 5.0-34.3). CONCLUSIONS: These findings can help identify patients with a particularly enduring risk of stroke who are most likely to benefit from ongoing monitoring and treatment and facilitate the development and implementation of targeted stroke prevention strategies.
3 May 2026
Read appraisal →JMIR aging
Machine Learning-Derived Cardiovascular Aging Phenotypes From Cardiac Function and Stroke Risk in the UK Biobank: Cohort Study
BACKGROUND: Cardiovascular magnetic resonance (CMR) is widely used across various cardiac conditions and systematically assesses cardiac anatomical structures and functional dynamics. Machine learning (ML) can accurately predict outcomes and understand the inherent features of clinical data. OBJECTIVE: This study aimed to derive CMR phenotypes related to cardiovascular aging, investigate the relationship between these phenotypes and stroke risk, and relearn these phenotypes using supervised ML. METHODS: We enrolled 36,467 participants without stroke and extracted CMR parameters from the UK Biobank, with follow-up data extending until September 30, 2023. Using the generative topographic mapping technique, we identified latent grid nodes among participants and then derived phenotypes through agglomerative hierarchical clustering. We used supervised ML models to predict cardiac function phenotypes and used Cox proportional hazards models to assess the association between these phenotypes and long-term stroke risk. RESULTS: We enrolled 36,467 participants in the study. The mean age was 54.9 (SD 7.5) years, with 17,442 (47.8%) male participants. During a mean follow-up time of 14.7 (SD 1.1) years, 500 (1.4%) participants developed stroke and 664 (1.8%) participants died, respectively. After generative topographic mapping modeling, we identified 2 distinct phenotypes: phenotype 1, characterized by adverse cardiac function and an accumulation of cardiovascular risk factors, reflecting cardiovascular aging; and phenotype 2, associated with a lower risk of stroke (hazard ratio 0.695, 95% CI 0.559-0.864; P=.001), which remained significant after accounting for competing mortality (hazard ratio 0.578, 95% CI 0.484-0.691; P<.001). We selected the random forest model as the optimal model for the phenotypes, demonstrating high accuracy (area under the curve 0.914, 95% CI 0.911-0.918 for training and 0.867, 95% CI 0.858-0.876 for validation) and calibration ability (Brier score 0.111, 95% CI 0.109-0.113 for training and 0.132, 95% CI 0.127-0.137 for validation). CONCLUSIONS: By integrating unsupervised and supervised ML methods, we identified cardiovascular aging-related phenotypes that demonstrate robust predictive ability for incident stroke, which may have the potential to improve preventive and therapeutic strategies for high-risk populations.
2 May 2026
Read appraisal →PloS one
A secondary head-to-head comparison of low-intensity focused ultrasound and repetitive transcranial magnetic stimulation for motor recovery after stroke
BACKGROUND: Low-intensity focused ultrasound (LIFU) is a non-invasive neuromodulation technique with high spatial precision and the ability to reach deeper brain regions, offering potential advantages for post-stroke rehabilitation. Repetitive transcranial magnetic stimulation (rTMS) is a widely adopted non-invasive brain stimulation technique that modulates cortical excitability to promote neuroplasticity. However, direct head-to-head comparisons between these two modalities for post-stroke motor recovery remain limited. OBJECTIVE: To perform a secondary head-to-head comparison of LIFU and repetitive transcranial magnetic stimulation (rTMS) for motor recovery after stroke, based on a prospectively registered randomized controlled trial. METHODS: This secondary analysis included patients with subacute stroke who received two weeks of standard rehabilitation combined with either LIFU (n = 25) or rTMS (n = 25) targeting the ipsilesional primary motor cortex. LIFU parameters: 0.5 MHz, spatial-peak pulse-average intensity (ISPPA) 10.2 W/cm² (free-field), pulse duration 0.2 ms, duty cycle 20%, 20 minutes per session, five days per week for two weeks (10 sessions total). rTMS parameters: 10 Hz, 80% resting motor threshold, 1,000 pulses per session (20 trains of 5 seconds), 20 minutes per session, five days per week for two weeks (10 sessions total). Motor outcomes were assessed using the Fugl-Meyer Assessment (FMA; upper and lower extremities), Modified Barthel Index (MBI), and Brunnstrom stages. Resting-state functional near-infrared spectroscopy (fNIRS) was used to evaluate cortical activity and functional connectivity before and after the intervention. Primary analyses were conducted in the intention-to-treat (ITT) population (n = 50), with completer analyses (n = 43) performed as sensitivity analyses. RESULTS: Both groups showed significant within-group improvements in FMA and MBI after the intervention (all p < 0.001), and changes in Brunnstrom stages were also uniformly significant. No statistically significant between-group differences were observed in post-intervention FMA, MBI, or Brunnstrom stages (all p > 0.05), and completer analyses yielded consistent between-group conclusions. In contrast, change-from-baseline analyses demonstrated greater improvements in FMA scores in the LIFU group compared with the rTMS group (ΔFMA upper limb: median 7 [IQR 3-10.5] vs. 2 [1-3], p = 0.001; lower limb: 3 [1-4.5] vs. 1 [0-1.5], p < 0.001). Exploratory fNIRS analyses revealed modality-specific patterns: prefrontal fractional amplitude of low-frequency fluctuations (fALFF) increased significantly in the LIFU group (p = 0.002) but not in the rTMS group, while functional connectivity changes did not remain significant after correction for multiple comparisons. CONCLUSION: LIFU and rTMS were associated with comparable short-term motor outcomes in subacute stroke. Differences observed in change-from-baseline motor improvements and exploratory neuroimaging measures suggest potential divergence in recovery dynamics and cortical modulation, warranting further investigation in larger, longitudinal studies. TRIAL REGISTRATION: This study was derived from a prospectively registered, three-arm randomized controlled trial in the Chinese Clinical Trial Registry (ChiCTR2500114687). The present manuscript reports a secondary head-to-head comparison between the two neuromodulation intervention arms.
27 Apr 2026
Read appraisal →Journal of ethnopharmacology
Neuroprotective effects of Tongxinluo capsule in acute ischemic stroke: A systematic review and meta-analysis
ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo capsule is widely used in patients with acute ischemic stroke (AIS), although the literature does not consistently agree on its efficacy and safety. AIM OF THE STUDY: We aimed to assess the efficacy and safety of Tongxinluo capsule for patients with AIS. MATERIALS AND METHODS: A systematic search of the databases PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang data, VIP Chinese Journal Service Platform, and SinoMed was conducted from their inception dates to January 2025. Randomized controlled trials (RCTs) that enrolled patients with AIS who receive Tongxinluo capsule and compared effects with placebo or as an add-on therapy to usual care were included. Literature screening, risk of bias assessment, and data extraction were independently conducted in duplicate. Fixed-effects or random-effects models were used to perform meta-analysis for pooling data from eligible studies. The primary outcome was long-term functional independence (defined as modified Rankin Scale [mRS] grade less than 2). Secondary outcomes included all-cause mortality, improvements in activities of daily living (measured with the Barthel Index [BI]), and neurological impairment (measured with the National Institutes of Health Stroke Scale [NIHSS]). Incidence of adverse events were identified as safety outcomes. RESULTS: We included 4842 patients with AIS from 12 RCTs (2422 [50.02 %] treated with Tongxinluo capsule) in the final analysis. Tongxinluo capsule treatment in AIS significantly improved the proportion of patients with mRS less than 2 (RR, 1.21; 95 % CI, 1.02 to 1.44), improved the change in BI score (MD, 11.47; 95 % CI, 10.34 to 12.60) and NIHSS score (MD, 3.48; 95 % CI, 2.87 to 4.09). No significant differences were detected in all-cause mortality (RR, 0.57; 95 % CI, 0.17 to 1.95), or the incidence of overall adverse events (RR, 1.01; 95 % CI, 0.91 to 1.12). CONCLUSION: Administration of Tongxinluo capsule for AIS demonstrated potential benefits in improving the long-term functional outcomes and activities of daily living, and relieving neurological impairment, without observing major safety concerns.
25 Apr 2026
Read appraisal →American journal of physical medicine & rehabilitation
Optimal Strategy of Resistance Training Combined With Other Rehabilitation Interventions for Lower-Limb Dysfunction in Stroke Patients: A Systematic Review and Network Meta-Analysis
OBJECTIVE: Stroke frequently results in lower-limb dysfunction, severely limiting independence. This study compared the effectiveness of resistance training alone and resistance training combined with other rehabilitation modalities in improving poststroke lower-limb function. DESIGN: A systematic review and Bayesian network meta-analysis were conducted following PRISMA guidelines. Randomized controlled trials involving resistance training alone or in combination with other therapies versus daily care or resistance training alone were included. The primary outcomes were balance, lower-limb motor function, and walking ability. RESULTS: Forty-seven trials with 2448 participants were analyzed. Resistance training combined with electrical stimulation therapy produced the greatest improvements in balance and lower-limb motor function, while resistance training combined with stretching training showed the best enhancement in walking ability. Surface Under the Cumulative Ranking Curve rankings indicated resistance training plus electrical stimulation therapy as most effective for balance (91.13%) and lower-limb motor function (79.70%), and resistance training plus stretching training for walking ability (96.34%). CONCLUSIONS: Resistance training remains fundamental in stroke rehabilitation. Integrating resistance training with targeted adjunctive training particularly electrical stimulation therapy or stretching training yields superior therapeutic outcomes and supports individualized, evidence-based strategies for optimizing lower-limb recovery after stroke.
25 Apr 2026
Read appraisal →The Cochrane database of systematic reviews
Delivery arrangements for rehabilitation services in health systems: an overview of systematic reviews
BACKGROUND: Cochrane Rehabilitation and the World Health Organization (WHO) Rehabilitation Programme have collaborated to produce four Cochrane overviews of systematic reviews synthesizing evidence from health policy and systems research (HPSR) in rehabilitation. Each overview focuses on one of the four HPSR pillars identified by the Cochrane Effective Practice and Organisation of Care (EPOC) taxonomy: delivery, financial, and governance arrangements; and implementation strategies. This overview addresses delivery arrangements, which Cochrane EPOC defines as how health services are organized and delivered, including who provides care, how care is coordinated and managed, and where services are provided. OBJECTIVES: This overview aimed to synthesize current evidence on delivery arrangements in rehabilitation from an HPSR perspective. Our series of four overviews has the following overarching objectives. • To offer a broad synthesis of existing evidence on health policy and systems interventions' effects. • To direct end-users, including policymakers, towards systematic reviews that may address their health policy questions. • To identify current research gaps and set priorities for future primary HPSR. • To pinpoint needs and priorities for new evidence syntheses where no reliable, up-to-date systematic reviews currently exist. METHODS: We searched Epistemonikos Health Systems Evidence databases and EPOC Group systematic reviews with no language limitations to identify reviews published between 2015 and 17 November 2024. We included Cochrane systematic reviews (CSRs) and non-CSRs of randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) evaluating the effectiveness of health policy and systems interventions for rehabilitation in health systems, specifically related to delivery arrangements as defined in the EPOC taxonomy. All four overview teams screened reviews and extracted data. We used AMSTAR 2 to critically appraise the reviews, and we analyzed the results descriptively. MAIN RESULTS: We included 25 systematic reviews. Three overlapped, and for 17 the AMSTAR 2 rating was low or critically low confidence. Five systematic reviews (2 CSRs and 3 non-CSRs) contributed to our synthesis. Most outcomes focused on patients, caregivers, or service use (e.g. access to rehabilitation). Equity-related outcomes were absent, and quality of care, adverse events, and our important outcomes were rarely reported. Below, we report the results of three of the five reviews judged to have moderate to high confidence for our outcomes of interest, in which authors conducted meta-analysis and assessed the certainty of the evidence. Who provides care One review analyzed advanced practice physiotherapy (APP) models, which may result in little to no difference in health-related outcomes measured by the Pain Disability Index and EuroQol 5-Dimension questionnaire after the intervention, compared with usual care in adults with spinal pain (standardized mean difference [SMD] 0.05, 95% confidence interval [CI] -0.32 to 0.42; 2 studies, 225 participants; low certainty). Information and communication technology We included two reviews in this category. One compared telerehabilitation with usual care in older adults, finding that telerehabilitation may have little or no effect on quality of life after seven to 20 weeks (SMD -0.09, 95% CI -0.23 to 0.40; 3 studies, 179 participants; low certainty). There was very low-certainty evidence on mobility after seven to 26 weeks (SMD 0.63, 95% CI -0.25 to 1.51; 5 studies, 302 participants), strength after 12 and 26 weeks (SMD 0.73, 95% CI -0.10 to 1.56; 4 studies, 226 participants), and balance after seven to 26 weeks (SMD 0.40, 95% CI -0.35 to 1.15; 3 studies, 199 participants). Another review on stroke survivors living in the community found that telerehabilitation compared with usual care probably has little or no effect on independence in activities of daily living (ADL) after 24 weeks (SMD 0.00, 95% CI -0.15 to 0.15; 2 studies, 661 participants; moderate certainty), self-reported quality of life after six to 24 weeks (SMD 0.03, 95% CI -0.14 to 0.20; 3 studies, 569 participants; moderate certainty), and depression after six to 24 weeks (SMD -0.04, 95% CI -0.19 to 0.11; 6 studies, 1145 participants; moderate certainty); and may have little or no effect on upper limb function after 12 weeks (SMD 0.33, 95% CI -0.21 to 0.87; 2 studies, 54 participants; low certainty) and mobility after six weeks (mean difference 0.01, 95% CI -0.12 to 0.14; 1 study; 144 participants; low certainty). This review also compared telerehabilitation with in-person rehabilitation and found that there may be little to no difference in independence in ADL, measured with the Modified Barthel Index at four to 12 weeks (MD 0.59, 95% CI -5.50 to 6.68; 2 studies, 75 participants; low certainty); balance, measured with the Berg Balance Scale at four to 12 weeks (MD 0.48, 95% CI -1.36 to 2.32; 3 studies, 106 participants; low certainty); and upper limb function, evaluated with the Fugl-Meyer Assessment (Upper Extremity) four weeks after intervention (MD 1.23, 95% CI -2.17 to 4.64; 3 studies, 170 participants; low certainty). AUTHORS' CONCLUSIONS: Current evidence on delivery arrangements in rehabilitation is limited, mostly of low certainty, and derived from high-income countries. Reviews covered five EPOC categories, but reliable evidence for our outcomes of interest was available for only two categories. Most evidence was on telerehabilitation. Compared with usual care, APP models may have little to no effect on health outcomes in adults with spinal pain. In people with stroke, telerehabilitation compared with usual care probably has little or no effect on independence in daily living, quality of life, and depression, and may have little to no effect on upper limb function and mobility. Compared with in-person care, telerehabilitation may have little to no effect on ADL, balance, and upper limb function. Further high-quality research using well-defined frameworks is needed, especially in low- and middle-income countries, to identify effective strategies and evaluate organizational, implementation, and equity outcomes. Future Cochrane overviews in HPSR should consider a broader range of study designs, such as observational, qualitative, and mixed-design evidence, to better capture evidence on delivery arrangements in rehabilitation. FUNDING: PC, CK, and SN were supported and funded by the Italian Ministry of Health (Ricerca Corrente). The funder played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. REGISTRATION: Protocol (2025): DOI 10.23736/S1973-9087.24.08833-6.
25 Apr 2026
Read appraisal →Journal of Korean medical science
Comparison of Clinical and Radiological Outcomes Between Suction Aspiration and Combination Methods of Mechanical Thrombectomy in Patients With Acute Cerebral Infarction: The COMPETE Trial
BACKGROUND: Recent advances in suction catheter technology suggest that suction aspiration may prevent thrombus fragmentation during mechanical thrombectomy. We therefore hypothesize that the radiological outcomes of suction aspiration as a first-line treatment would not be inferior to those of the combination technique. This study aims to evaluate the radiological and clinical outcomes of first-line suction aspiration compared with those of the first-line combination technique for large artery occlusion amenable to both modalities. METHODS: The COMPETE trial is a prospective, randomized, multicenter, noninferiority, open-label trial. A total of 1,136 patients will be randomized at a 1:1 ratio to either the suction aspiration or combination technique groups. RESULTS: The primary endpoints are successful recanalization (modified Thrombolysis in Cerebral Infarction scale score ≥ 2b) and a good clinical outcome (modified Rankin Scale score of 0-2) at 90 days after thrombectomy. The technical outcome is the switching rate from the combination technique to suction aspiration and from suction aspiration to the combination technique. The safety outcomes include procedural morbidity, nonprocedural morbidity, procedural mortality, and nonprocedural mortality. CONCLUSION: The COMPETE trial is expected to determine whether the use of suction aspiration as a first-line approach in patients with acute ischemic stroke is noninferior to the combination technique in achieving successful radiological and good clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06254755; CRIS (KCT0007726).
23 Apr 2026
Read appraisal →Journal of neurology
The association of night shift work with the risk of acute ischemic cerebrovascular syndrome: a longitudinal study of 204,261 UK Biobank participants
BACKGROUND: Shift work is highly prevalent globally, yet evidence linking it to ischemic cerebrovascular disease remains inconsistent. Existing studies are limited by unsystematic quantification of night shift exposure and outcome definitions failing to capture the clinical continuum of ischemic events. We performed a large prospective cohort study using refined shift pattern classification and acute ischemic cerebrovascular syndrome (AICS) as the primary end point to enable a robust evaluation of the association between shift patterns and ischemic cerebrovascular disease. METHODS: 204,261 participants with employment information from the UK Biobank were included. Cox proportional hazards regression was used to assess associations between current shift work and AICS risk, with cross-classification by shift status and job duration. We further quantified average lifetime night shift frequency and cumulative duration among participants with complete occupational histories. Transient ischemic attack (TIA) and ischemic stroke (IS) were analyzed separately to identify the main driver of AICS and potential heterogeneity. RESULTS: During a median follow-up exceeding 14 years, irregular shift work was significantly associated with elevated AICS risk (HR 1.118, 95% CI 1.019-1.227, P = 0.019), while always night shift work was not (HR 0.904, 95% CI 0.707-1.157, P = 0.423). AICS risk was driven by irregular shift patterns rather than duration. Lifetime night shift frequency and duration showed significant dose-response relationships with AICS. CONCLUSIONS: Irregular shift work increases AICS risk relative to non-shift work, and lifetime night shift exposure exhibits a clear dose-response effect. IS constitutes the primary driver of the composite AICS end point.
20 Apr 2026
Read appraisal →PloS one
The association between RDW-to-platelet ratio and in-hospital mortality in critically ill stroke patients: A retrospective cohort study based on the eICU database
OBJECTIVE: The red cell distribution width-to-platelet ratio (RDW-to-platelet ratio, RPR) is a potential biomarker of inflammation and bone marrow function. This study aimed to investigate the association between RPR and in-hospital mortality in critically ill stroke patients in the eICU, and to evaluate mediating role of APACHE-IV score. METHOD: This retrospective cohort study utilized data from the 2014-2015 US multicenter eICU database. Of 200,859 initially included patients, 9,736 critically ill stroke patients were analyzed after excluding non-stroke cases and those with missing key variables. Multivariable logistic regression assessed the relationship between RPR and in-hospital mortality, adjusting for age, sex, comorbidities, and laboratory parameters, with multiple imputation for missing data. Subgroup analyses, mediation analysis, and restricted cubic spline modeling were performed. RESULTS: Patients with higher RPR exhibited significantly elevated in-hospital mortality (17.7% vs. 11.6%, P < 0.001). After adjustment, each unit increase in RPR was associated with 4.6% higher odds of death (adjusted OR=1.046, 95% CI: 1.032-1.061, P < 0.001), with consistent findings across subgroups. Restricted cubic spline analysis indicated a linear relationship. Mediation analysis showed that APACHE-IV score mediated 20.15% of the total effect (P < 0.001). CONCLUSIONS: Elevated RPR is independently associated in-hospital mortality in critically ill stroke patients, partly mediated by disease severity. As a simple and accessible marker, RPR shows promise for clinical prognostic risk stratification.
18 Apr 2026
Read appraisal →Journal of neurointerventional surgery
Systolic blood pressure within 24 hours after successful reperfusion correlates with outcomes in acute ischemic stroke: a secondary analysis of the EHCHANTED2/MT Trial
BACKGROUND: The optimal threshold or range for systolic blood pressure (SBP) control in patients with successful reperfusion after endovascular thrombectomy for acute ischemic stroke (AIS) remains undefined. This study investigated whether SBP within the first 24 hours after successful reperfusion correlates with functional outcomes in AIS. METHODS: In this secondary analysis of the ENCHANTED2/MT trial, patients were categorized into two groups (120-140 mm Hg and 140-180 mm Hg, respectively) based on achieved SBP within 24 hours after randomization. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included neurological deterioration at 7 days, major disability (mRS score of 3-5 at 90 days), hospitalization duration, and health-related quality of life assessed by the three-level EuroQoL 5-Dimension Self-Report Questionnaire (EQ-5D-3L) at 90 days. Safety outcomes included early neurological decline (END), 90-day mortality, symptomatic intracranial hemorrhage (sICH), and any intracranial hemorrhage (ICH). Treatment effects were expressed as ORs with 95% confidence intervals (CIs). RESULTS: A total of 611 patients (363 in the 120-140 mm Hg group and 248 in the 140-180 mm Hg group) were included. The mean (SD) age was 67 (12) years and 37.8% were female. After adjusting for confounders, the 120-140 mm Hg group was significantly associated with better functional outcomes (mRS: 2 (IQR 1-4) vs 2 (IQR 1-5); adjusted OR 1.54 (95% CI 1.10 to 2.17), P=0.013). Compared with the 140-180 mm Hg group, the 120-140 mm Hg group had lower rates of neurological deterioration at 7 days (adjusted OR 0.68 (95% CI 0.47 to 0.98), P=0.037) and 90-day mortality (47 (13.0%) vs 53 (21.4%); adjusted OR 0.48 (95% CI 0.27 to 0.86), P=0.013). There were no significant differences between groups in END, major disability at 90 days, hospitalization duration, EQ-5D-3L score, sICH, or ICH (all P>0.05). CONCLUSIONS: In patients with successful reperfusion after endovascular thrombectomy, an average SBP within 24 hours of 120-140 mm Hg was associated with a greater likelihood of functional independence compared with 140-180 mm Hg.
18 Apr 2026
Read appraisal →Journal of global health
Associations between haemoglobin-to-red cell distribution width ratio and mortality in intracerebral haemorrhage: a population-based analysis of the MIMIC-IV database
BACKGROUND: Intracerebral haemorrhage (ICH) is a leading cause of mortality and morbidity worldwide. Identifying early prognostic biomarkers is crucial to optimise clinical management of critically ill patients with ICH. The haemoglobin-to-red cell distribution width ratio (HRR) has recently emerged as a potential predictor in various critical illnesses, but its role in ICH remains unclear. This study aimed to evaluate associations between HRR and mortality in patients with ICH. METHODS: This retrospective cohort study included the data of adults (≥18 years) extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database (version 1). HRR was calculated from the first available haemoglobin and RDW measurements within one day of each other. Patients were categorised into HRR quartiles. The primary outcomes were 28-day and 1-year all-cause mortality. Associations were assessed using Cox proportional hazards models. RESULTS: The data of 1915 patients (mean age 67.5 years) were analysed retrospectively. After adjusting for possible confounders, compared with the lowest HRR quartile (Q1), patients in Q3 and Q4 had significantly lower 28-day mortality (Q3: adjusted hazard ratio (aHR) = 0.72; 95% CI = 0.54, 0.97; Q4: aHR = 0.67; 95% CI = 0.49, 0.90). Similarly, higher HRR quartiles were associated with reduced 1-year mortality risk (Q3: aHR = 0.64; 95% CI = 0.49, 0.84; Q4: aHR = 0.56; 95% CI = 0.42, 0.75). CONCLUSIONS: Lower HRR at admission is independently associated with higher short-term and long-term mortality in ICU patients with ICH. HRR may serve as a candidate prognostic biomarker for early risk stratification in this high-risk population. Further prospective studies are warranted to confirm these findings.
18 Apr 2026
Read appraisal →Journal of neurointerventional surgery
Explainable machine learning model for predicting functional outcomes in posterior circulation stroke after thrombectomy
BACKGROUND: The early prediction of functional outcomes in patients with posterior circulation stroke (PCS) is crucial for timely interventions and optimizing treatment plans. We have developed and validated a machine learning (ML) model for predicting 3-month functional outcomes in patients with PCS undergoing endovascular thrombectomy (EVT). METHODS: The derivation cohort, consisting of 202 patients with PCS who underwent EVT at four medical centers from January 2020 to December 2023, was separated for training and internal validation, and an external dataset of 54 patients admitted from January 2020 to July 2023 was used for external validation. The target outcome was a good functional outcome, defined as a modified Rankin Scale score of 0-3 at 3 months. Seven ML models were trained using preoperative features, with the primary evaluation metric being the area under the receiver operating characteristic curve (AUC). The top performing model was further trained using intraoperative and postoperative features. Model interpretations were generated using the Shapley additive explanations (SHAP) method. RESULTS: The Random Forest model demonstrated the best discriminative ability among the models considered. After feature selection, the final preoperative model used seven features, achieving an AUC of 0.83 in the test set and 0.81 in the external validation cohort. The inclusion of intraoperative and postoperative features further enhanced the model's performance, resulting in an AUC of 0.84 and 0.90 in the test set and 0.83 and 0.90 in the external validation cohort, respectively. These models have been incorporated into a publicly accessible web-based calculator (https://zhelvyao-123-60-basilarz.streamlit.app). CONCLUSION: The interpretable ML models provide dynamic accurate predictions of functional outcomes in patients with PCS after EVT, offering valuable insights for personalized risk stratification and optimizing perioperative management, with potential for integration into clinical workflows.
18 Apr 2026
Read appraisal →Journal of neurointerventional surgery
Stroke thrombectomy with a novel reperfusion system including a 0.088'' aspiration catheter: the Imperative Trial
BACKGROUND: Mechanical thrombectomy is the standard of care for large vessel occlusion (LVO) stroke, yet most device trials focus on individual technologies rather than complete systems. OBJECTIVE: To evaluate the safety and efficacy of the Zoom Reperfusion System compared with performance goals derived from a meta-analysis of trials using established thrombectomy technologies. METHODS: Prospective, multicenter, non-randomized, investigational device exemption trial conducted across 26 United States centers from October 2021 to March 2024. Adults with anterior circulation LVO stroke within 8 hours of onset were treated using the Zoom System, which includes aspiration catheters ranging from 0.035″ to 0.071″, and a novel 0.088″ intracranial guide/aspiration catheter. The primary efficacy endpoint was successful reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) 2b-3) within three passes using Zoom-only components, adjudicated by an independent core laboratory. The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Secondary outcomes included final reperfusion, first-pass success, time to reperfusion, 90-day modified Rankin Scale (mRS), and mortality. RESULTS: Among 260 patients (median age 68 years; median National Institutes of Health Stroke Scale (NIHSS) 15), successful reperfusion within three passes was achieved in 83% (216/259; 95% CI: 78% to 89%), exceeding the performance goal (p<0.001). Final reperfusion was 92%, with 5.5% requiring rescue devices. First-pass mTICI 2b-3 success was 57%. Median puncture-to-reperfusion time was 19 min. At 90 days, 55% achieved mRS 0-2. The sICH rate was 1.9%, and 90-day mortality was 12.7%. CONCLUSIONS: The Zoom Reperfusion System demonstrated a safety and efficacy profile exceeding prespecified contemporary performance metrics with potential to significantly shorten reperfusion times and reduce the need for rescue therapy. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov--Identifier:NCT04129125.
17 Apr 2026
Read appraisal →Journal of neurointerventional surgery
Intravascular lithotripsy in calcified carotid stenosis: technical and clinical outcomes
INTRODUCTION: Carotid artery stenosis (CAS) is a major cause of stroke, disability, and mortality worldwide. While medical therapy and revascularization remain the cornerstones of management, both surgical and endovascular approaches can be limited by complex anatomy and heavily calcified plaques, which increase procedural risk. Intravascular lithotripsy (IVL), originally developed for coronary and peripheral interventions, has recently emerged as a potential strategy for plaque modification in CAS. By delivering localized shockwave pulses, IVL fractures vascular calcium, facilitating safer angioplasty and stent deployment. However, its use in CAS remains off-label and poorly described. METHODS: A systematic search of PubMed, Google Scholar, and Embase was conducted in September 2025 in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies included patients with CAS undergoing IVL with reported procedural success and/or clinical outcomes. Risk of bias was assessed using the Joanna Briggs Institute (JBI) appraisal tools. RESULTS: Fifteen studies comprising 120 patients were included. The mean age ranged from 50 to 82 years, and the degree of stenosis from 70%-95%. Technical success was reported in 100% of cases. Across the pooled cohort, 101 of 120 patients (84.2%) achieved residual stenosis ≤30%. Seven patients (5.8%) experienced ipsilateral stroke or transient ischemic attack within 30 days. CONCLUSION: IVL for CAS is an emerging therapy demonstrating consistent technical feasibility and favorable short-term safety across published studies. These findings suggest that IVL may benefit patients with complex calcified plaques at high risk for standard revascularization; however, randomized controlled trials are needed to confirm its role in clinical practice.
17 Apr 2026
Read appraisal →Journal of rehabilitation medicine
Does aerobic exercise affect memory, attention, working memory, and fatigue after acquired brain injury? A single-blinded, randomized controlled pilot study.
OBJECTIVE: To explore potential effects of aerobic exercise on cognitive function, fatigue, and neuroplasticity after stroke or traumatic brain injury. DESIGN: A randomized controlled pilot study. SUBJECTS/PATIENTS: Twelve participants, 10 men and 2 women aged 16-65 years diagnosed with acquired brain injury (moderate to severe stroke or traumatic brain injury), enrolled in an outpatient rehabilitation programme at least 3 months post-injury. METHODS: The intervention group (n = 6) participated in 30 min of aerobic exercise 3-4 times/week for 8 weeks during their outpatient rehabilitation. The control group (n = 6) received routine physical therapy. In addition, both groups received rehabilitation according to their rehabilitation plan. Neuropsychological and endurance testing was performed before and after the intervention and at a 3-month follow-up. Functional magnetic resonance imaging was performed before and after the intervention. RESULTS: Preliminary findings show no significant difference between the groups regarding cognitive variables, fatigue, or neuroplasticity. However, working memory/executive demanding processing speed, measured with the Paced Auditory Serial Addition Test, improved significantly (p = 0.042) in the aerobic exercise group and there were trends of improvements on several other executive tests in the aerobic exercise group. Automatic visual search speed improved in the control group (p = 0.027). CONCLUSION: The question of whether aerobic exercise promotes cognition and fatigue after brain injury remains unanswered. This randomized controlled pilot study and its preliminary findings indicate greater improvements in executive processing speed in the aerobic exercise group, while more automatized attention speed improved more in the control group. The experiences from this study might facilitate the design of future studies on this intriguing topic. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT07429526.
17 Apr 2026
Read appraisal →Scientific reports
Predicting post-stroke functional outcome using explainable machine learning and integrated data
Functional outcome after acute ischemic stroke (AIS) varies widely, and existing prognostic scores may not capture complex relationships. We evaluated a diverse set of clinical characteristics and blood biomarkers with multiple machine learning models to predict 3-month functional outcome after AIS, and used explainable artificial intelligence to identify key drivers of performance. Models were trained on 506 patients aged 18-69 years with AIS enrolled at four stroke units in western Sweden. We compared extreme gradient boosting, multilayer perceptron (MLP), and L1- and L2-regularized logistic regression. Feature importance was assessed with Shapley additive global explanations. Of the 506 patients, 105 had an unfavorable outcome (modified Rankin Scale score > 2). All models showed high area under the curve (AUROC, 0.900-0.906). The MLP achieved the highest precision-recall performance (AUPRC, 0.773 ± 0.080) and sensitivity (0.655 ± 0.096), though with lower specificity (0.920 ± 0.035). Stroke severity (NIH Stroke Scale score) was the dominant predictor across models. Among biomarkers, brain-derived tau (BD-tau) was most informative, followed by inflammation-related plasma proteins. In conclusion, machine learning accurately predicted functional outcome after AIS. BD-tau and inflammation-related proteins contributed predictive information above stroke severity, suggesting a potential for blood biomarkers to enhance individualized prognostication after AIS.
17 Apr 2026
Read appraisal →The New England journal of medicine
Asundexian for Secondary Stroke Prevention
BACKGROUND: Patients with noncardioembolic ischemic stroke or transient ischemic attack (TIA) are at risk for recurrent stroke. Low factor XI levels are associated with a reduced risk of ischemic stroke. Asundexian inhibits activated factor XI. Whether the addition of asundexian to antiplatelet therapy would be superior to antiplatelet therapy alone for the secondary prevention of ischemic stroke is unclear. METHODS: In this phase 3, double-blind trial, we randomly assigned patients within 72 hours after the onset of a noncardioembolic ischemic stroke or high-risk TIA to receive asundexian (50 mg once daily) or placebo, in addition to planned dual or single antiplatelet therapy. Patients had at least one of the following: a nonlacunar infarct on imaging, a history of atherosclerosis, or evidence of atherosclerotic plaque at any location on cerebrovascular imaging. The primary efficacy outcome was ischemic stroke. The composite of death from cardiovascular causes, myocardial infarction, or stroke was a key secondary outcome. The primary safety outcome was major bleeding. RESULTS: Among 12,327 patients who underwent randomization (6162 to the asundexian group and 6165 to the placebo group), the incidence of ischemic stroke was lower in the asundexian group than in the placebo group (6.2% vs. 8.4%; cause-specific hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.84; P<0.001). The incidence of the composite of death from cardiovascular causes, myocardial infarction, or stroke was lower in the asundexian group than in the placebo group. The incidence of major bleeding was similar in the asundexian group and the placebo group (1.9% and 1.7%, respectively; cause-specific hazard ratio, 1.10; 95% CI, 0.85 to 1.44). The incidence of adverse events was 69.3% in the asundexian group and 70.1% in the placebo group; the incidence of serious adverse events was 19.2% and 19.5%, respectively. CONCLUSIONS: Among patients with noncardioembolic ischemic stroke or high-risk TIA treated with antiplatelet therapy, asundexian at a daily dose of 50 mg resulted in lower risks of ischemic stroke and major cardiovascular events than placebo, without a higher risk of major bleeding. (Funded by Bayer; OCEANIC-STROKE ClinicalTrials.gov number, NCT05686070.).
16 Apr 2026
Read appraisal →JMIR mHealth and uHealth
Effect of a Comprehensive Mobile-Based Respiratory Training Program on Respiratory Function in Survivors of Acute Stroke: Randomized Controlled Trial
BACKGROUND: Respiratory dysfunction frequently occurs during the acute phase of stroke and is associated with reduced ventilatory capacity, respiratory muscle weakness, and increased pulmonary complications. However, delivering standardized respiratory training during hospitalization is often constrained by staffing and service continuity. OBJECTIVE: This study aimed to evaluate the efficacy, safety, and feasibility of a hospital-based comprehensive mobile-based respiratory training program (CMRTP) added to conventional rehabilitation in people with acute stroke who are inpatients. METHODS: This single-center, assessor-blinded randomized controlled trial enrolled 40 patients within 2 weeks after stroke onset with respiratory dysfunction (forced vital capacity <80% predicted). Participants were randomized (1:1) to CMRTP plus conventional rehabilitation or conventional rehabilitation alone. The CMRTP was delivered via the WeChat-based AIRHUB platform and performed 20 minutes twice daily, 5 days per week for 2 weeks, either independently or with caregiver assistance as needed. The primary outcome was change in forced vital capacity from baseline to week 2. Secondary outcomes included forced expiratory volume in 1 second (FEV₁), peak expiratory flow, maximal inspiratory pressure, maximal expiratory pressure, and modified Barthel index. All outcomes were assessed face-to-face by a blinded senior physician, and all analyses followed an intention-to-treat principle. RESULTS: Of 56 screened patients, 40 were randomized, and 39 completed the study. Adherence to the CMRTP reached 96%, and no serious adverse events occurred; mild, transient events (fatigue, dizziness, and hyperventilation) were recorded. Compared with the control group, the CMRTP group demonstrated greater improvement in forced vital capacity at week 2 (mean difference 0.77 L; 95% CI 0.39-1.16; P<.001; η²=0.32), with additional between-group differences in maximal inspiratory pressure (P=.001; η²=.25), maximal expiratory pressure (P<.001; η²=.08), and modified Barthel index (P=.001; η²=.26). No significant group differences were found for forced expiratory volume in 1 second or peak expiratory flow. CONCLUSIONS: A 2-week hospital-based mobile respiratory training program is feasible and safe in people with acute stroke who are inpatients and yields clinically meaningful improvements in respiratory function and daily functional performance when added to conventional rehabilitation.
15 Apr 2026
Read appraisal →Neurology
Outcomes After Minor Ischemic Stroke in Older Patients Treated With IV Thrombolysis vs Standard of Care in the TEMPO-2 Trial
BACKGROUND AND OBJECTIVES: There are few high-quality data on thrombolysis outcomes in the oldest patients, especially for minor stroke. We examined safety and efficacy outcomes of thrombolysis in patients older than 80 years, compared with those ≤80 years, in the Tenecteplase Versus Standard of care for Minor Ischaemic Stroke With Proven Occlusion (TEMPO-2) trial. METHODS: In this post hoc analysis of the TEMPO-2 randomized controlled trial, we compared outcomes and adverse events in patients with minor stroke and symptomatic intracranial occlusion or focal perfusion lesion within 12 hours of symptom onset, assigned to tenecteplase vs nonthrombolytic standard of care, in those >80 years and ≤80 years. The primary outcome was responder analysis of the 90-day modified Rankin Scale (responder was mRS = 0-1 if premorbid mRS = 0-1, 0-2 if premorbid mRS = 2). Secondary outcomes included neurologic recovery according to the NIH Stroke Scale (NIHSS) at 5 days/discharge, vessel recanalization, Lawton Instrumental Activities of Daily Living Scale, EuroQol-5 Dimension (EQ-5D), and adverse events. We used mixed-effects Poisson, ordinal logistic, and quantile regression as appropriate, adjusted for sex, baseline NIHSS, and treatment assignment as fixed-effects and enrolling site as random effects. RESULTS: Among 884 patients in the intention-to-treat analysis (208 [23.5%] >80 years, 365 [41.6%] female). Significant interactions between age and treatment were observed for mRS responder, mRS 0-1, return to baseline function, EQ-5D index, and vessel recanalization. Patients >80 years generally fared worse with tenecteplase for mRS outcomes (mRS 0-1 in 49 [46.2%] vs 61 [59.8%] with control, adjusted risk ratio [aRR] 0.83, 95% CI 0.72-0.97), while among patients ≤80 years, there was no significant difference (249 [76.4%] vs 260 [74.7%], aRR 1.01, 95% CI 0.98-1.03). However, in both age groups, patients were more likely to achieve recanalization of visible occlusions (aRR ≤80 years 2.06, 95% CI 1.60-2.65, >80 years 2.77, 95% CI 2.21-3.47) and NIHSS = 0 at 5 days/discharge when assigned to tenecteplase (aRR ≤80 years 1.14, 95% CI 1.04-1.26, >80 years 1.21, 95% CI 1.10-1.33). Serious adverse events (SAEs) were more frequent with tenecteplase among patients >80 years (risk ratio 2.29, 95% CI 1.27-4.13), particularly hemorrhages and stroke progression/recurrence (any extra/intracranial hemorrhage in 5 [4.7%] vs 0 with standard of care, p = 0.026). DISCUSSION: Older patients (>80 years) with minor stroke and visible occlusion or perfusion lesion assigned to tenecteplase were more likely to achieve recanalization of occlusions and short-term neurologic recovery, as were younger patients, but they experienced worse 90-day outcomes with more frequent hemorrhagic and stroke progression/recurrence-related SAEs. Overall, these results, while post hoc, do not support thrombolysis for minor strokes in older patients. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT02398656. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients >80 years with minor stroke and visible occlusion or perfusion lesion, IV thrombolysis with tenecteplase is associated with worse functional outcomes at 90 days compared with nonthrombolytic standard of care therapies.
15 Apr 2026
Read appraisal →Neurology
Systolic Blood Pressure Trajectory and Outcomes in Acute Intracerebral Hemorrhage: Pooled Analysis of the 4 INTERACT and ATACH-II Clinical Trials
BACKGROUND AND OBJECTIVES: While moderate and rapid systolic blood pressure (SBP) lowering was associated with better functional outcomes after intracerebral hemorrhage (ICH), large reductions in SBP within 1 hour, for example, reductions from >200 to <140 mm Hg, diminished or even reversed these beneficial effects. We aimed to define the optimal trajectory of SBP control in relation to favorable functional outcomes after acute ICH. METHODS: We conducted a pooled analysis of individual patient-level data from all 4 Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) and second Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) trials, which were international, randomized, open-label, blinded, end point-assessed, controlled trials that determined the effectiveness of early intensive SBP control in acute ICH. Latent class analysis grouped SBP trajectories over the first 24 hours (9 measurements) into defined clusters. The primary outcome was functional recovery at 90 days after randomization, defined as modified Rankin Scale (mRS) scores of 3-6. Logistic regression models with adjustment for baseline covariates and trial were used to determine associations between SBP cluster trajectories and outcomes in INTERACT, with validation in ATACH-II. RESULTS: A total of 11,269 patients (INTERACT n = 10,269; ATACH-II n = 1,000; mean age 62.4 years; female 36.4%) with at least 1 postrandomization SBP reading were included. Six SBP trajectories were identified: low, moderate-to-low, moderate, high, high-to-moderate, and high-to-low. Compared with the low SBP group, associations with poor functional outcome (mRS scores 3-6) increased progressively across other groups in INTERACT (p = 0.04 for trend). Adjusted odds ratios (95% CI) for groups 2 to 6 were 1.16 (0.98-1.37), 1.44 (1.18-1.75), 1.46 (1.15-1.87), 1.90 (1.32-2.73), and 1.28 (1.02-1.60), respectively. A similar albeit nonsignificant trend was observed in ATACH-II due to limited power. DISCUSSION: Distinct SBP trajectories over 24 hours defined prognosis after ICH, with a severe hypertensive group having the highest odds of death or disability, regardless of the BP-lowering strategy used. These findings highlight the importance of well-controlled but tailored SBP management strategies after ICH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that distinct SBP trajectories over 24 hours are associated with prognosis after acute ICH, with a severe hypertensive group having the highest odds of poor functional outcome, regardless of the BP-lowering strategy used. TRIAL REGISTRATION INFORMATION: (INTERACT1 NCT00226096; INTERACT2 NCT00716079; INTERACT3 NCT03209258; INTERACT4 NCT03790800; ATACH-2 NCT01176565).
15 Apr 2026
Read appraisal →Science advances
Filament sensing tension: A bionic artificial tendon for self-force-regulated artificial muscle-driven wearable robotics
Artificial muscles have been in development for decades and play a crucial role in the field of wearable robotics. However, a universal device for both sensing and regulating forces in artificial muscles is still absent, rendering scenario-required force control unfeasible. Inspired by Golgi tendon organs, this work proposes bionic ExoTendon for force sensing and regulating in artificial muscles as a general solution. Leveraging the principles of triboelectrification and electrostatic induction, the ExoTendon offers high linearity, minimal hysteresis, and adjustable sensitivity and range, making it suitable as the tendon of artificial muscles. Specifically, the ExoTendon effectively enable adjustment to the pretension of the artificial muscles, yielding various assistive forces under the same input. With the optimized pretension level and closed-loop force control, the artificial muscle-based exosuit achieves self-force regulation, substantially improving walking balance and speed in stroke subjects under low input, demonstrating its promise in wearable robotics and rehabilitation medicine.
9 Apr 2026
Read appraisal →PloS one
Dizziness in the emergency department and risk of stroke: A systematic review and meta-analysis
BACKGROUND: Dizziness is a frequent emergency department (ED) presentation, and a subset of patients, especially those with isolated dizziness without focal neurological deficits, have stroke but are prone to misdiagnosis and adverse outcomes. Reported stroke prevalence in ED dizziness cohorts is highly heterogeneous, and comprehensive assessments of isolated dizziness remain limited. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Web of Science, Embase, and the Cochrane Library for relevant studies. We included cross-sectional studies reporting stroke prevalence among all ED patients with dizziness or isolated dizziness. A random-effects model was used for meta-analysis to calculate pooled prevalence. Subgroup analyses and Egger's test were employed to explore heterogeneity and publication bias. The diagnostic accuracy of bedside diagnostic tools was also systematically reviewed. RESULTS: Twenty-nine studies involving 161,013 ED patients presenting with dizziness were included. The pooled stroke prevalence among all ED dizziness patients (n = 158,583) was 5.5% (95% CI: 4.1-7.1). Among patients with isolated dizziness (n = 2,559), the pooled prevalence was 13.9% (95% CI: 8.2-20.9), substantially higher than in the overall dizziness cohort. Subgroup analyses indicated diagnostic methods and hospital level as major contributors to heterogeneity. Summary analysis of bedside diagnostic tools showed that HINTS and STANDING examinations have high diagnostic accuracy overall, while the TriAGe+ score can be applied flexibly for screening or confirmation based on different cut-off points. CONCLUSIONS: ED patients with dizziness carry a meaningful, setting-dependent stroke risk. Standardized bedside exams (HINTS, STANDING) improve early triage, and selectively deploying neuroimaging helps prevent missed strokes when risk is high.
9 Apr 2026
Read appraisal →Journal of the American Heart Association
Effects of Computed Tomography Hyperdense Middle Cerebral Artery Sign on the Efficacy of Endovascular Therapy in Acute Ischemic Stroke With Large Infarcts: A Subgroup Analysis of the ANGEL-ASPECT Trial
BACKGROUND: The hyperdense middle cerebral artery sign (HMCAS) observed on noncontrast computed tomography is associated with thrombus composition and thrombectomy outcomes. The impact of HMCAS on the efficacy of endovascular therapy (EVT) in patients with large core infarcts remains unclear. METHODS: This analysis uses data from the ANGEL-ASPECT (Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core) trial, a multicenter randomized controlled trial conducted in China. Patients with acute ischemic stroke and anterior-circulation large-vessel occlusion were categorized according to whether HMCAS was present on baseline noncontrast computed tomography. The primary outcome was the 90-day modified Rankin Scale score. RESULTS: Of the 432 patients included in this analysis, 33% were HMCAS positive on baseline noncontrast computed tomography. In the EVT-treated patients, patients with HMCAS had worse functional outcomes than those without HMCAS (adjusted relative risk, 0.44 [95% CI, 0.26-0.73]; P=0.002). Patients with HMCAS required a greater number of thrombectomy passes (P<0.001). Among patients without HMCAS, EVT was associated with better functional outcomes than medical management (generalized odds ratio [OR], 2.78 [95% CI, 1.80-4.27]; P<0.001), whereas this benefit was not statistically significant among patients with HMCAS (adjusted OR, 1.69 [95% CI, 0.93-3.08]; P=0.09). There was no significant interaction between HMCAS status and treatment assignment (P=0.19). CONCLUSIONS: In this subgroup analysis comparing EVT with medical management, we found no statistically significant treatment-by-HMCAS status interaction, indicating that the benefits of EVT extend to patients with large core infarcts irrespective of HMCAS status. However, the magnitude of benefit appears greater in patients without HMCAS, whereas those with HMCAS tend to have a poorer overall prognosis. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04551664.
9 Apr 2026
Read appraisal →JAMA
Tenecteplase for Acute Non-Large Vessel Occlusion 4.5 to 24 Hours After Ischemic Stroke: The OPTION Randomized Clinical Trial
IMPORTANCE: The efficacy and safety of intravenous tenecteplase in non-large vessel occlusion acute ischemic stroke beyond 4.5 hours after symptom onset remain uncertain. OBJECTIVE: To assess the efficacy and safety of intravenous tenecteplase administered 4.5 to 24 hours after stroke onset in patients with non-large vessel occlusion and salvageable brain tissue. DESIGN, SETTING, AND PARTICIPANTS: This randomized, open-label, blinded end-point clinical trial was conducted at 48 centers in China. A total of 566 patients with non-large vessel occlusion stroke and evidence of potentially salvageable tissue determined on perfusion imaging presenting within 4.5 to 24 hours of the time last seen well were recruited between June 2, 2023, and August 4, 2025 (final follow-up, October 28, 2025). INTERVENTIONS: Patients were randomly assigned 1:1 using a minimization algorithm to receive intravenous tenecteplase (0.25 mg/kg; maximum dose, 25 mg; n = 282) or standard medical treatment (n = 284). MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin Scale at 90 days. Safety outcomes included symptomatic intracranial hemorrhage within 36 hours and mortality within 90 days. RESULTS: Among the 570 patients randomized, 566 were included in the primary analysis (median age, 68 [IQR, 59-75] years; 196 female [34.6%]). An excellent functional outcome was observed in 123 of 282 patients (43.6%) in the tenecteplase group and 97 of 284 (34.2%) in the control group (risk ratio, 1.28 [95% CI, 1.04-1.57]; P = .02). The incidence of symptomatic intracranial hemorrhage at 2.8% was higher with tenecteplase than with standard medical treatment at 0% (risk difference, 2.85% [95% CI, 1.16%-5.54%]; P = .004), and the mortality at 90 days was 5.0% and 3.2%, respectively (risk ratio, 1.57 [95% CI, 0.69-3.57]; P = .28). CONCLUSIONS AND RELEVANCE: Among patients with non-large vessel occlusion acute ischemic stroke and salvageable brain tissue, intravenous tenecteplase administered 4.5 to 24 hours after onset resulted in a greater likelihood of an excellent functional outcome at 90 days than standard care but had an increased risk of symptomatic intracranial hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05752916.
8 Apr 2026
Read appraisal →Journal of the American Heart Association
A Position Statement on Endovascular Models and Effectiveness Metrics for Mechanical Thrombectomy Navigation, on Behalf of the Stakeholder Taskforce for Artificial Intelligence-Assisted Robotic Thrombectomy (START)
Although we are making progress in overcoming infectious diseases and cancer, one of the major medical challenges of the mid-21st century will be the increasing prevalence of stroke. Occlusions in large vessels are especially debilitating, yet effective treatment-needed within hours to achieve best outcomes-remains limited because of geographic accessibility. One solution for improving timely access to mechanical thrombectomy in geographically diverse populations is the widespread deployment of robotic surgical systems. Artificial intelligence assistance may enable the safe and effective upskilling of operators in this emerging therapeutic delivery approach. Our aim was to establish consensus frameworks for developing and validating artificial intelligence-assisted robots for thrombectomy. Objectives included standardizing effectiveness metrics and defining reference testbeds across in silico, in vitro, ex vivo, and in vivo environments. To achieve this, we convened experts in neurointervention, robotics, data science, health economics, policy, statistics, and patient advocacy. Consensus was built through an incubator day, a Delphi process, and a final position statement. We identified that the 4 essential testbed environments each had distinct validation roles. Realism requirements vary: simpler testbeds should include realistic vessel anatomy compatible with guidewire and catheter use, whereas standard testbeds should incorporate deformable vessels. More advanced testbeds should include blood flow, pulsatility, and disease features, such as atheromatous plaques. There are 2 macroclasses of effectiveness metrics: one for in silico, in vitro, and ex vivo stages focusing on technical navigation (eg, path-following error), and another for in vivo stages, focused on clinical outcomes (eg, modified treatment in cerebral infarction scores). Patient safety is central, and not a barrier, to this technology's development. One requisite patient safety task needed now is to correlate in vitro measurements to in vivo complications.
8 Apr 2026
Read appraisal →Journal of the American Heart Association
Development and Validation of a Machine Learning Model to Predict Oral Anticoagulant Use in Stroke From Prothrombin Time-International Normalized Ratio and Activated Partial Thromboplastin Time
BACKGROUND: Timely recognition of oral anticoagulant use is critical in acute stroke but is often hampered by impaired consciousness and unavailable medication history. We investigated whether routinely available coagulation tests, prothrombin time-international normalized ratio and activated partial thromboplastin time, paired with machine learning can identify anticoagulant exposure at presentation. METHODS: We performed a multicenter diagnostic modeling study using the Japan Stroke Data Bank. Adults with ischemic or hemorrhagic stroke admitted in 2016 to 2021 comprised the derivation cohort; those in 2022 formed a temporally distinct validation cohort. Three models (random forest, extreme gradient boosting, and neural network) used prothrombin time-international normalized ratio and activated partial thromboplastin time as predictors to classify anticoagulant status: vitamin K antagonist, direct oral anticoagulant, or none. Discrimination (area under the receiver operating characteristic curve and area under the precision-recall curve), calibration, and decision curve analysis were assessed. Model outputs were implemented as bedside probability heat maps. RESULTS: Among 30 767 patients (derivation n=24 857; validation n=5910), vitamin K antagonist/direct oral anticoagulant use was 4.5%/8.2% in derivation and 2.8%/9.5% in validation. In the validation cohort, the neural network yielded the best performance: area under the receiver operating characteristic curve, 0.933 (95% CI, 0.908-0.955) and area under the precision-recall curve, 0.52 (95% CI, 0.44-0.61) for vitamin K antagonist; area under the receiver operating characteristic curve, 0.841 (95% CI, 0.822-0.858) and area under the precision-recall curve, 0.39 (95% CI, 0.35-0.43) for direct oral anticoagulant, with preserved calibration and highest net benefit across clinically relevant thresholds. Heat maps summarized class probabilities over the prothrombin time-international normalized ratio×activated partial thromboplastin time space to support rapid inference. CONCLUSIONS: A simple machine learning model using only prothrombin time-international normalized ratio and activated partial thromboplastin time classified vitamin K antagonist and direct oral anticoagulant exposure with high accuracy and practical clinical utility. This tool assists emergency decision-making when medication history is unknown, supporting the safety and timeliness of acute stroke care.
8 Apr 2026
Read appraisal →PloS one
A multi-modal data fusion and real-time monitoring on stroke risk prediction using federated learning
Predicting the risk of stroke is one of the critical problems in healthcare, which necessitates efficient solutions for providing accurate and prompt risk assessments while preserving data confidentiality. This work proposes a new framework using Federated Learning (FL) to combine Multi-Layer Perceptron (MLP) and Gated Recurrent Unit (GRU) models that are essential in analyzing multimodal data. Implemented in Python, the approach incorporates two datasets: Dataset 1, which consists of Demographic data medical history, and lifestyle data, and the second dataset, which includes the normal condition and the affected stroke condition CT scan images. Imputation of missing values, feature normalization by Min-Max scaling, and handling of imbalanced classes with SMOTE make the data pre-processing procedures exhaustive. In FL architecture three clients -Client A, Client B, and Client C - process a split multimodal dataset containing static and sequential information. Each client independently trains an MLP-GRU model. Each is applied with MLP handling static features from Dataset 1 and GRU handling sequential features from Dataset 2. To update models, Federated Averaging is used on a central server, to create a global model that is then returned to the clients for further refinement. The accuracy of the proposed method averages 99.00% and surpasses other models by 2.5% including CNN, LSTM, Random Forest, and SVM. By enhancing MLP with GRU and applying them to a privacy-preserving FL framework,The study addresses the fragmented use of multimodal medical data, where clinical records and imaging are generally evaluated separately, resulting in inadequate diagnostic support. The strategy integrates complementary modalities to create a more comprehensive perspective of patient health, enhancing healthcare predictive accuracy and decision-making. This incentive is essential for improving computational methods and linking technical advancement with medical objectives like fast diagnosis and therapy planning. The introduction emphasises the therapeutic necessity of harmonising organized and unstructured data to reduce diagnostic ambiguity. A translational approach is used to discuss how multimodal integration might improve clinical workflows, develop collaborative healthcare systems, and support sustainable medical practices. This repeated emphasis links methodological advances to real-world healthcare issues, boosting the study's academic relevance sets.
7 Apr 2026
Read appraisal →Neuroscience
Comparative analysis of key phagocytic genes in humans and mice using machine learning integrated with single-cell RNA sequencing
Microglial phagocytosis is essential for neurological recovery after intracerebral hemorrhage (ICH). Using single-cell RNA sequencing, we compared microglial responses in murine and human ICH and identified striking species-specific temporal patterns. Murine microglia exhibited a sustained enhancement of phagocytic activity, whereas human microglia showed only a transient increase followed by a decline and persistent inflammation. To identify genes associated with phagocytic differences, we evaluated five machine learning models and selected XGBoost as the best-performing model. This analysis identified Tlr2 in mice and CLEC7A in humans as genes associated with microglial phagocytic status. Inferred transcription factor activity analysis further revealed stronger phagocytosis- and inflammation-associated transcriptional activity in murine phagocytic microglial subclusters, whereas human microglia were predominantly characterized by inflammation-associated transcription factors. Consistent with these results, Tlr2 expression was markedly increased at day 14 in single-cell data, and immunostaining confirmed its colocalization with IBA1+ microglia and upregulation at days 3 and 7 after ICH. Together, our findings demonstrate that integrating single-cell RNA sequencing with machine learning facilitates the identification of phagocytosis-associated genes and reveals both conserved and divergent patterns of microglial phagocytosis, providing new insights into species-specific responses to ICH.
6 Apr 2026
Read appraisal →Medicine
Prediction model for frailty risk in ischemic stroke patients: Application and validation of support vector machines and nomograms
This study aimed to develop a prediction model based on nomograms and support vector machines (SVM) to assess frailty risk in ischemic stroke patients. Clinical information of ischemic stroke patients admitted to our hospital from January 2023 to December 2024 was retrospectively collected. First, independent risk factors associated with frailty in ischemic stroke patients were identified through univariate and multivariate logistic regression analyses. Subsequently, a nomogram was constructed based on regression analysis results and validated using 10-fold cross-validation. Data were divided into training (70%) and validation (30%) sets. A SVM predictive model was constructed on the training set. The predictive performance of both models was compared using receiver operating characteristic curves. This study included 867 ischemic stroke patients, among whom 296 (34.14%) were classified as frail. The entire cohort was randomly divided into a training set (n = 607) and a validation set (n = 260) at a 7:3 ratio. Logistic regression analysis identified hypertension, impaired self-care ability, physical inactivity, reduced prognosis nutrition index, and depressive status as independent risk factors for frailty in ischemic stroke patients (P < .05). The nomogram demonstrated an area under the receiver operating characteristic curve (AUC) of 0.814 for frailty prediction, while the SVM model achieved an AUC of 0.842, indicating superior predictive capability. Further comparison revealed that while the nomogram offers greater intuitiveness and operational convenience in clinical practice, the SVM model demonstrated superior predictive accuracy. Hypertension, impaired self-care ability, physical inactivity, reduced prognosis nutrition index, and depressive states are independent risk factors for frailty in ischemic stroke patients. Both predictive models (nomogram and SVM) demonstrated high predictive accuracy; however, the SVM model outperformed the nomogram in predictive capability, while the latter retains unique advantages due to its simplicity and clinical applicability.
5 Apr 2026
Read appraisal →AJNR. American journal of neuroradiology
Delphi Consensus on Early Neurologic Improvement after Mechanical Thrombectomy
BACKGROUND AND PURPOSE: Early neurologic improvement (ENI) following mechanical thrombectomy (MT) has been a topic of substantial interest. The literature has more than 40 ENI definitions, yet no consensus has been reached. In this Delphi study, we sought to investigate experts' perspectives on the available ENI definitions and determine whether a consensus can be achieved. MATERIALS AND METHODS: The Delphi approach assessed experts' perspectives on available ENI definitions. Following a systematic literature review, the first survey round was prepared and sent to 20 experts using a Web-based anonymous survey platform (qualtrics.com). The first round of questions was publicly shared on the letsgetproof.com platform to gather perspectives of neurointerventionalists worldwide on ENI definitions. Expert and volunteer answers formed the basis of subsequent rounds, in which closed-ended questions were sent only to experts. Consensus was defined as an agreement of ≥70% for binary closed-ended questions and ≥50% for closed-ended questions with >2 response options. RESULTS: Experts completed 3 survey rounds. They recognized that the heterogeneity in ENI definitions is the most critical factor limiting the use of ENI in clinical practice and stroke research. All experts acknowledged that stroke physicians need a standardized universal ENI definition. Consensus was reached on the notion that a unified ENI definition should focus on predicting functional independence at 3 months. They agreed that NIHSS improvement of ≥8 points at 24 hours could serve as the unified ENI definition. They acknowledged that incorporating prestroke comorbidities, occlusion location, baseline NIHSS scores, and procedure-related parameters would complicate the ideal ENI definition and limit its use in clinical settings. The experts could not reach a consensus on the potential utility of ENI as a primary end point in MT trials. CONCLUSIONS: In our Delphi analysis, experts agreed on an ENI definition. They did not endorse using different ENI criteria for patients with comorbidities, posterior circulation occlusions, or high baseline NIHSS scores. Further prospective studies are needed to validate or refine ENI definitions and to address the paucity of data on the prognostic utility of ENI in specific clinical scenarios.
5 Apr 2026
Read appraisal →AJNR. American journal of neuroradiology
Reliability of Pseudocontinuous Arterial Spin-Labeling in Ischemic Stroke and Comparison with Other Perfusion Techniques: Systematic Review and Meta-Analysis
BACKGROUND: Pseudocontinuous arterial spin-labeling (pCASL) is a noninvasive, gadolinium-free MRI technique for assessing brain perfusion. PURPOSE: The test-retest reliability of pCASL-derived CBF measurements in ischemic stroke (IS) were evaluated and pCASL metrics were compared with those from DSC, CTP, and PET. DATA SOURCES: Systematic searches were conducted in MEDLINE, EMBASE, and LILACS. Risk of bias and methodologic quality were evaluated using QUADAS-2 and Quality Appraisal for Reliability Studies tools. STUDY SELECTION: Eleven studies, encompassing 383 participants with IS were included. DATA ANALYSIS: Random-effects meta-analysis with inverse variance method and heterogeneity assessed using I 2 statistics were used. DATA SYNTHESIS: No PET studies were identified. Only 1 low-quality, high-risk-of-bias study assessed test-retest reliability, finding no significant differences in repeated absolute CBF measurements over time and excellent reliability across regions. Most studies comparing pCASL with DSC, and all comparing pCASL with CTP, had a low risk of bias. In the hyperacute phase of IS, pCASL and DSC showed no significant differences in infarct core relative CBF (95% CI, -0.11 to 0.13; I 2 = 0%) or hypoperfusion volumes (95% CI, -0.28 to 0.68; I 2 = 69%). Evidence on the comparability of pCASL with other DSC or CTP metrics was limited. LIMITATIONS: The small number of included studies prevented a meta-analysis for the primary outcome and limited conclusions for secondary outcomes. CONCLUSIONS: Robust conclusions about the test-retest reliability of pCASL or the comparability of metrics obtained with this technique and DSC, CTP, or PET in different phases after IS could not be drawn.
5 Apr 2026
Read appraisal →AJNR. American journal of neuroradiology
Flow Diversion versus Coiling with or without Stenting for Unruptured Wide-Neck Intracranial Aneurysms: A Randomized Comparison
BACKGROUND AND PURPOSE: There are few randomized trials comparing coiling (with or without stent placement) and flow diversion (FD) for the treatment of wide-neck unruptured intracranial aneurysms. MATERIALS AND METHODS: EVIDENCE was an investigator-led randomized (1:1) trial conducted in 7 French university hospitals. Patients with 7 to 20-mm intradural unruptured intracranial aneurysms with a 4- to 10-mm neck and a "dome/neck" ratio of ≥1 were randomly allocated to coiling with or without adjunctive stent placement or FD alone. The composite primary efficacy outcome was "treatment failure," defined as initial failure to treat the aneurysm; aneurysm rupture or retreatment during follow-up; death or dependency (mRS> 2); or an angiographic residual aneurysm adjudicated by an independent core laboratory at 12 months. The primary hypothesis (revised for slow accrual) was that FD would decrease treatment failures from 35% to 10%, requiring 90 patients. Primary analyses were intent to treat. RESULTS: Among the 91 enrolled patients, four (two in each group) withdrew consent; 87 patients were included in the analysis: 43 in the FD group and 44 in the control group. Most patients had <10 mm (57/87; 65.5%) asymptomatic ophthalmic aneurysms (75/87, 86.2%). A poor primary outcome, ascertainable in 86 patients, was reached in 8/43 patients with FD (18.6%; 95% CI, 9.7%-32.6%) compared with 10/43 coiling patients (23.3%; 95 CI, 13.1%-37.7%) (RR = 0.80; 95% CI, 0.35-1.83; P = .60). Serious adverse events were similar. CONCLUSIONS: For patients with mostly unruptured, wide-neck ophthalmic aneurysms of <10 mm, FD was not superior to coiling with or without stent placement.
5 Apr 2026
Read appraisal →The New England journal of medicine
Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation
BACKGROUND: Catheter-based closure of the left atrial appendage is an alternative to oral anticoagulation for stroke prevention in patients with atrial fibrillation. The effectiveness of this strategy, as compared with physician-directed best medical care, in patients at high risk for stroke and bleeding is unknown. METHODS: In this multicenter randomized trial conducted in Germany, we assigned patients with atrial fibrillation and a high risk of stroke and bleeding to undergo left atrial appendage closure or to receive physician-directed best medical care (including direct oral anticoagulants, if eligible). The primary end point, tested for noninferiority, was a composite of stroke (ischemic or hemorrhagic), systemic embolism, major bleeding, or cardiovascular or unexplained death, assessed in a time-to-event analysis. The noninferiority margin was a hazard ratio of 1.3. RESULTS: A total of 912 adult patients underwent randomization. The primary end-point analysis included 446 patients who were assigned to undergo left atrial appendage closure (device group) and 442 who were assigned to physician-directed best medical care (medical-therapy group). The mean (±SD) age was 77.9±7.1 years; 38.6% of the patients were women, the mean CHA2DS2-VASc score was 5.2±1.5 (range, 0 to 9, with higher scores indicating a greater risk of stroke), and the mean HAS-BLED score was 3.0±0.9 (range, 0 to 9, with higher scores indicating higher risk of bleeding). After a median follow-up of 3 years (interquartile range, 1.7 to 4.7), a first primary end-point event had occurred in 155 patients (incidence per 100 patient-years, 16.8) in the device group and in 127 patients (incidence per 100 patient-years, 13.3) in the medical-therapy group (difference in restricted mean survival time, -0.36 years; 95% confidence interval, -0.70 to -0.01; P = 0.44 for noninferiority). Serious adverse events occurred in 368 patients (82.5%) in the device group and 342 (77.4%) in the medical-therapy group. CONCLUSIONS: Among patients with atrial fibrillation at high risk for stroke and bleeding, left atrial appendage closure was not noninferior to physician-directed best medical care with regard to a composite end point of stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death. (Funded by the German Center for Cardiovascular Research; CLOSURE-AF ClinicalTrials.gov number, NCT03463317.).
4 Apr 2026
Read appraisal →Stroke
Balancing Innovation and Responsibility: Ethical and Privacy Challenges in Stroke Digital Health
Digital health solutions are being increasingly used to support care delivery across various medical fields. In stroke care, technology has contributed to enhancing prehospital workflows, facilitating communication among health care professionals, and enabling fast-track systems for hyperacute stroke management. Furthermore, digital tools are used to improve etiological diagnosis and allow for more tailored long-term follow-up of stroke patient survivors. Digital technologies have become an integral part of stroke management, and the rapid evolution of artificial intelligence continues to accelerate and drive this transformation. However, ethical and privacy considerations are central and represent a major challenge for the design and implementation of digital solutions in health care. Health care professionals involved in stroke care require a clear understanding of the digital tools they use, including their potential, limitations, and biases, and must be aware of the responsibilities inherent in relying on such systems for treatment decisions and outcome prediction. This topical review aims to examine current digital innovations in stroke care, with a particular focus on the key ethical and privacy challenges they raise.
4 Apr 2026
Read appraisal →AJNR. American journal of neuroradiology
Multimodal CT Perfusion-Based Deep Learning for Predicting Stroke Lesion Outcomes in Complete and No Recanalization Scenarios
BACKGROUND AND PURPOSE: Predicting the final location and volume of lesions in acute ischemic stroke is crucial for clinical management. While CTP is routinely used for estimating lesion outcomes, conventional threshold-based methods have limitations. We developed specialized outcome-prediction deep learning models that predict infarct core in successful reperfusion cases and the combined core-penumbra region in unsuccessful reperfusion cases. MATERIALS AND METHODS: We developed single-modal and multimodal deep learning models using CTP parameter maps to predict the final infarct lesion on follow-up DWI. Using a multicenter data set from multiple sites, we developed deep learning models and evaluated them separately for patients with complete recanalization (successful reperfusion [CR], n = 350) and no recanalization (unsuccessful reperfusion [NR], n = 138) after treatment. The CR model was designed to predict the infarct core region, while the NR model predicted the expanded, hypoperfused tissue encompassing both the core and penumbra regions. Five-fold cross-validation was performed for robust evaluation. RESULTS: The multimodal 3D nnU-Net model demonstrated superior performance, achieving mean Dice scores of 35.36% in patients with CR and 50.22% in those with NR. This model substantially outperformed the current clinically used method, providing more accurate outcome estimates than the conventional single-technique threshold-based measures, which yielded Dice scores of 15.73% and 39.71% for CR and NR groups, respectively. CONCLUSIONS: Our approach offered both successful reperfusion and unsuccessful reperfusion estimations for potential treatment outcomes, enabling clinicians to better evaluate treatment eligibility for reperfusion therapies and assess potential treatment benefits. This advancement facilitates more personalized treatment recommendations and has the potential to substantially enhance clinical decision-making in acute ischemic stroke management by providing more accurate tissue outcome predictions than conventional single-technique threshold-based approaches.
4 Apr 2026
Read appraisal →Journal of medical Internet research
Predictive Value of Machine Learning for Poststroke Mortality Risk: Systematic Review and Meta-Analysis
BACKGROUND: People with stroke face a high mortality risk, and an accurate prediction model is essential to the guidance of clinical decision-making in this population. Recently, with growing attention paid to machine learning (ML) in stroke care, some researchers have investigated the effectiveness of ML in predicting the mortality risk in stroke. However, systematic evidence is still lacking for its effectiveness. OBJECTIVE: This systematic review aims to evaluate the value of ML in predicting the stroke mortality risk. The findings are expected to offer an evidence-based basis for developing and assessing clinical risk prediction tools. METHODS: A search was made in Cochrane Library, PubMed, Embase, and Web of Science up to June 23, 2025, and studies that reported a complete performance of ML in predicting stroke mortality were included. Studies with only risk factors analyzed were excluded. The risk of bias of the included studies was assessed using PROBAST (Prediction model Risk of Bias Assessment Tool). Pooled risk ratios with 95% CIs and prediction intervals (PIs) were derived using the Hartung-Knapp-Sidik-Jonkman method under a random-effects model. Subgroup analyses were also conducted by model type, stroke type, patient source, and treatment background. Moreover, a metaregression was conducted on the C-index for out-of-hospital mortality at different time points to explore the influence of time factors on the model's predictive performance. RESULTS: Sixty-eight studies were included (23 predicting in-hospital mortality and 45 predicting out-of-hospital mortality), describing the development of 75 prediction models and 43 external validations. The follow-up period was 1 month to 15 years. For predicting in-hospital mortality, the external validation set had a pooled C-index of 0.727 (95% CI 0.677-0.781, 95% PI 0.521-1.000), with sensitivity and specificity of 0.64 (95% CI 0.57-0.70) and 0.74 (95% CI 0.70-0.77), respectively. For predicting out-of-hospital mortality, the pooled C-index was 0.847 (95% CI 0.808-0.887, 95% PI 0.750-0.956) in the external validation set, with sensitivity and specificity of 0.71 (95% CI 0.55-0.82) and 0.76 (95% CI 0.74-0.78), respectively. Comparatively, the overall pooled C-indexes were 0.788 (95% CI 0.766-0.810, 95% PI 0.621-0.999) and 0.812 (95% CI 0.798-0.826, 95% PI 0.693-0.952), respectively. The metaregression revealed a gradual decline in the predictive performance of the overall model and logistic regression model alone, whereas a random forest model maintained sustained performance. Age, National Institutes of Health Stroke Scale score, and stroke-related complications were the most frequently used variables for modeling. CONCLUSIONS: This is the first meta-analysis to demonstrate that ML-based prediction of stroke mortality is feasible. The performance of ML supports its role as an auxiliary tool for identifying high-risk populations, thereby optimizing clinical monitoring and resource allocation. However, due to substantial heterogeneity and a relatively high risk of bias in available studies, caution is warranted in real-world application. The effectiveness of ML may vary across settings, and external validation is recommended before broader implementation. TRIAL REGISTRATION: PROSPERO CRD420251086321; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251086321.
4 Apr 2026
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