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Patient-reported experience measures (PREM) are key indicators of healthcare quality linked to improved outcomes. The Canadian Stroke Best Practice Recommendations emphasise the importance of capturing patient perceptions of health services to enhance clinical outcomes in stroke care. Building on our previously established stroke-specific PREM, this quality improvement (QI) observational project aimed to gather stroke patient experience data to identify strengths and opportunities for improvement. This QI initiative was implemented in an acute stroke unit as part of the mobile transient ischaemic attack (TIA) and stroke with adaptive workflow project funded by Ontario's Ministry of Health. An interdisciplinary team of healthcare professionals and leadership members developed a survey focusing on patient journey themes. The survey was reviewed for readability and comprehension by two patients to ensure its appropriateness and relevance. The Institute for Healthcare Improvement model guided the initiative, with a project lead identifying eligible patients and a reactivation worker administering the surveys. A total of 110 patients with stroke or TIA completed the survey over a 12-month observational period. Positive experience rates ranged from 90.0% to 99.1% across all seven domains, and no respondent selected disagree or strongly disagree on any item. Discharge readiness was the lowest-rated domain (90%), whereas a coordinated transition to the stroke unit achieved the highest ratings (99.1%). Inductive thematic analysis of open-ended responses identified three themes: (1) overall satisfaction, gratitude and quality of care; (2) patient-centred communication and emotional support and (3) isolated concerns. This QI initiative, building on previous work, showed positive patient experiences across all seven domains, with discharge readiness as a priority for improvement. The mixed-methods approach, which integrates quantitative Likert data with thematic analysis, offers a replicable model for patient-centred quality monitoring of stroke care.

Patent foramen ovale (PFO) is a recognized risk factor for cerebral ischemia. Hypercoagulable states are additional cofactors that may increase the risk of ischemic stroke. In this review, we aimed to summarize current knowledge on coagulation disorders and analyze how the coexistence of PFO and thrombophilia influences the risk of cerebral ischemia. We conducted a literature search of the PubMed database to identify studies examining the coexistence of PFO and thrombophilia, as well as their impact on the risk of cerebral ischemia. We found that selected hypercoagulable states, especially the prothrombin G20210A mutation and, to a lesser extent, antiphospholipid antibodies and factor V Leiden mutation are associated with a higher risk of cerebral ischemia in PFO patients. Moreover, we investigated the role of percutaneous PFO closure in patients with hypercoagulability. Percutaneous PFO closure is a safe and effective therapeutic strategy for secondary prevention of cerebral ischemia. Furthermore, some studies suggest that it may also be explored in the context of primary prevention in selected patients with hypercoagulability; however, this approach is not currently supported by clinical guidelines. Further studies are needed to clarify the role of thrombophilia in the management of patients with PFO-related stroke. Patent foramen ovale (PFO) is an opening between the upper chambers of the heart called atria. The PFO is present in the fetus and usually closes after birth. However, in more than 25% of adults, this opening remains present. Usually, PFO does not cause any symptoms, but in some cases it can be a contributing factor in the development of stroke, particularly among young adults. Thrombophilia is a condition in which the blood has an increased tendency to form clots. Thrombophilia may also predispose certain individuals to strokes.In our study we analyzed the evidence regarding the association of PFO, thrombophilia, and the risk of stroke. Current studies suggest that some types of thrombophilia may increase a risk of stroke in patients with PFO. Specifically, the prothrombin G20210A mutation and antiphospholipid antibodies are associated with an increased risk of stroke, while the factor V Leiden mutation is associated to a lesser extent. Nevertheless, the available studies are limited, and further research is required. The current literature is not sufficient to make management decisions.

Dizziness and vertigo are common and debilitating neurological symptoms among patients visiting the emergency department (ED). Possibly because the symptoms are not captured by standard stroke severity tools such as the NIHSS (National Institutes of Health Stroke Scale), their network-level neuroanatomical correlates-particularly potential supratentorial contributions-remain incompletely characterized. Therefore, we aim to investigate the neuroanatomical substrates of post-stroke dizziness and vertigo. This retrospective analysis included patients with acute ischemic stroke from the randomized controlled INSPiRE-TMS trial. Each patient underwent MRI within seven days of symptom onset, and stroke severity was assessed using the NIHSS at hospital admission. Patients were assessed for broadly defined new-onset dizziness/vertigo associated with the acute cerebrovascular event. Lesion symptom mapping (LSM) and lesion network mapping (LNM) were used to investigate associations between lesion location, functional connectivity, and dizziness/vertigo. Among 484 patients, 32% (n&#x2009;=&#x2009;157) reported dizziness at stroke onset. Notably, dizziness was reported in 22% (77/347) of patients with supratentorial lesions, compared with 58% (80/137) of those with infratentorial lesions. Patients with dizziness were more often female (36.9% vs. 27.8%, p&#x2009;=&#x2009;0.042) and more frequently had hemianopia (35.1% vs. 15.6%, p&#x2009;<&#x2009;0.0001). LSM identified cerebellar clusters (left lobules VI, Crus I-II, VIIb, VIIIa, and bilateral lobule IX with the vermis) associated with visuospatial and multisensory processing. LNM revealed a dizziness network involving left-dominant cerebellar regions, the brainstem, and higher-order visual areas, including the occipital pole, lingual gyrus, and fusiform gyrus. This network remained robust across subgroups stratified by lesion location (supra- vs. infratentorial) and after adjusting for age, sex, lesion volume, and hemianopia. Exploratory subtype comparisons suggested that lesions associated with vertigo showed relatively stronger connectivity to midline cerebellar structures (vermis), whereas those associated with swaying dizziness involved broader cerebellar hemispheres, although the overall network pattern was spatially similar and centered on the cerebellum. In conclusion, broadly defined post-stroke dizziness/vertigo symptoms were associated with a consistent lesion network involving cerebellar and occipital regions, suggesting involvement of distributed visual, vestibular, and multisensory brain systems. These findings may help guide future studies aimed at improving diagnostic evaluation and treatment of affected patients. ClinicalTrials.gov (NCT01586702; https://clinicaltrials.gov/ct2/show/NCT01586702 ); first registry in April 2012; first patient recruitment: September 2011.

Combined oral contraceptives (COCs) are often avoided in women with migraine because of concerns about ischemic stroke. However, the risk associated with low-dose and ultra-low-dose COCs remains unclear. We aimed to evaluate the risk of ischemic stroke using contemporary low-dose COC use among women with migraine. We conducted a retrospective cohort study using the JMDC claims database in Japan. Women aged 20-49&#x2009;years diagnosed with migraine between April 2012 and March 2024 were included. Exposure was defined as administration of COCs containing estrogen doses of 20 and 35&#x2009;&#x3bc;g, whereas the comparison group was defined as discontinued use after the initial prescription. The hazard ratios (HRs) for ischemic stroke were estimated using Cox regression, and odds ratios (ORs) were calculated using case-time-control analysis to evaluate short-term associations. Among the 215&#x2009;536 women with migraine, 453 experienced ischemic strokes during follow-up. Among COC continuing users, the 5-year cumulative incidence rates of ischemic stroke were 0.11% (95% CI: 0.01% to 0.81%), and the HR was 0.10 (95% CI: 0.01 to 1.36). The OR in the case-time-control analysis was 0.38 (95% CI: 0.03 to 5.13). This large claims database study found no significant increase in the risk of ischemic stroke or other outcomes associated with low-dose COC use in women with migraine.

Blood pressure-lowering treatment prevents stroke after spontaneous intracerebral haemorrhage. However, there is uncertainty over the consistency of the effects across clinically relevant subgroups as well as the time course over which benefits accrue. We aimed to pool individual-level data across diverse settings and treatment strategies to quantify the size, heterogeneity, and timing of the effects of blood pressure-lowering treatment for the secondary prevention of major cardiovascular endpoints in patients with a history of intracerebral haemorrhage. We did a systematic review and meta-analysis of identified randomised controlled trials evaluating long-term blood pressure-lowering for secondary prevention in adults with a history of spontaneous intracerebral haemorrhage. We searched Embase and Ovid MEDLINE, from database inception to Jan 25, 2026, with two authors (YG and MJV) independently screening titles, abstracts, and full-text articles for eligibility. Trials were eligible if they enrolled adults (aged 18 years or older) with previous spontaneous intracerebral haemorrhage, randomly assigned participants to fixed-dose antihypertensive therapy or an intensive, titrated target-based blood pressure-lowering strategy versus placebo or standard blood pressure management, and reported clinical outcomes. Stroke trials had available individual participant data for subgroups of at least 100 participants with acute intracerebral haemorrhage. Methodological quality was assessed using the Cochrane Risk of Bias 2 tool. The primary outcome was first recurrent stroke of any type. We pooled individual participant data with a one-stage intention-to-treat meta-analysis using Cox proportional hazards models, incorporating a random effect for trial and adjustment for prespecified covariates. Prespecified subgroup analyses included demographic variables and baseline blood pressure, with formal tests for treatment-by-subgroup interaction. We estimated the time to benefit for a clinically meaningful absolute risk reduction, defined as 1% risk difference. The protocol is registered with PROSPERO (CRD420251274994). Of 236 records screened, 37 trials were retrieved, 24 were assessed for eligibility after duplicates were removed, and four eligible trials provided individual participant data for analysis. 2944 participants were included in the meta-analysis. The mean age was 59&#xb7;6 years (SD 10&#xb7;6), 972 (33&#xb7;0%) were female, 1972 (67&#xb7;0%) were male, 2218 (75&#xb7;3%) were Asian, and the median follow-up was 42&#xb7;0 months (IQR 24&#xb7;0-66&#xb7;0). The mean systolic blood pressure difference between blood pressure-lowering treatment and control over follow-up was 11&#xb7;2 mm Hg (95% CI 10&#xb7;7-11&#xb7;7). Intensive blood pressure-lowering reduced the hazard of first recurrent stroke of any type compared with control (96 [6&#xb7;5%] of 1487 participants versus 152 [10&#xb7;4%] of 1457 participants; adjusted hazard ratio [HR] 0&#xb7;62, 95% CI 0&#xb7;48-0&#xb7;80; p=0&#xb7;0002). This finding was driven by fewer recurrent intracerebral haemorrhage events (33 [2&#xb7;2%] of 1487 participants on blood pressure lowering-treatment versus 81 [5&#xb7;6%] of 1457 control participants; adjusted HR 0&#xb7;39, 95% CI 0&#xb7;26-0&#xb7;59; p<0&#xb7;0001). Serious adverse events occurred in 429 (28&#xb7;9%) of 1487 patients in the intensive group and 481 (33&#xb7;0%) of 1457 patients in the control group. Treatment effects were consistent across prespecified subgroups (eg, age, sex, region, background blood pressure-lowering treatment, baseline blood pressure, and time since index event). The time to achieve a 1% absolute benefit was estimated to be 6&#xb7;1 months (95% CI 3&#xb7;5-14&#xb7;8). Intensive blood pressure-lowering treatment after spontaneous intracerebral haemorrhage reduces recurrent stroke, mainly by preventing recurrent haemorrhage, without evidence of excess serious adverse events. Effects were consistent across patient characteristics, including time since the index event and baseline level of blood pressure. The early accrual and durability of benefit after treatment initiation strengthens the case for sustained long-term blood pressure control as the cornerstone of secondary prevention after intracerebral haemorrhage. None.

Current recommended blood pressure (BP) targets during mechanical thrombectomy (MT) rely on a one-size-fits-all approach aiming at preventing hypertension. The efficacy and safety of an individualized BP control during thrombectomy for ischemic stroke has not been well studied. We aimed to evaluate whether an individualized BP control during MT could improve functional outcome at 90 days. We conducted a multicenter, open-label, blinded-endpoint, randomized clinical trial at 8 academic comprehensive stroke centers in France. Adult patients with an acute ischemic stroke due to an anterior large vessel occlusion and an indication for MT were eligible. Recruitment was performed between March 10, 2021, and September 18, 2023. Patients were randomly assigned (1:1) to an individualized BP group during MT (where the mean arterial pressure [MAP] was maintained within 10% of the first MAP measured before MT) or a control BP group (systolic BP maintained within 140 and 180 mm Hg). The primary outcome was favorable functional outcome, defined as a modified Rankin Scale score between 0 and 2 at 90 days. Safety outcomes included symptomatic intracranial hemorrhages at 24 hours and mortality at 90 days. Overall, 433 patients (median age, 69.3 years, 228 females [52.8%]) were assigned to an individualized BP group (n = 215) or the control BP group (n = 218); one was excluded because of consent withdrawal. No significant differences in mean BP levels or BP variability were observed between groups during the procedure. Favorable functional outcome at 90 days was observed in 94 patients (44.2%) in the individualized BP group and 106 patients (48.8%) in the control group (adjusted odds ratio, 0.82; 95% CI 0.54-1.24; p = 0.34). Mortality from any cause at 90 days was not significantly different between groups (18.8% in the individualized BP group vs 16.4% in the control BP group: adjusted odds ratio, 1.19; 95% CI 0.70-2.03). Rates of symptomatic intracranial hemorrhages were not different between the 2 groups. In patients with acute ischemic stroke due to an anterior large vessel occlusion, an individualized BP management during MT did not increase rates of favorable functional outcome at 90 days compared with a standard BP management. ClinicalTrials.gov, DETERMINE, number NCT04352296. This study provides Class II evidence that in patients undergoing mechanical thrombectomy for stroke due to anterior large vessel occlusion, functional outcomes at 90 days were similar with individualized BP management and standard BP management.

Intravenous thrombolytic therapy (IVT) is recommended for patients with acute ischemic stroke (AIS) and disabling deficits, regardless of National Institutes of Health Stroke Scale (NIHSS) score. The benefit of IVT in patients with mild AIS was, however, not documented in recent trials. The aim of this study was to evaluate the effectiveness of IVT in mild AIS in a nationwide registry-based study. AIS patients from the Norwegian Stroke Registry (2016-2022) with a National Institutes of Health Stroke Scale (NIHSS) score &#x2264; 5 at admission were included. Using 1:1 propensity score matching, 1736 IVT-treated patients were matched with 1736 controls. Primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 90&#x2009;days. Secondary outcomes included mRS 0-2, a favorable mRS shift (range 0-6), and death within 28 and 90&#x2009;days. Data on symptomatic intracerebral hemorrhage (sICH) were available only for the IVT group. At 90&#x2009;days, 68.4% of IVT-treated patients and 61.2% of controls achieved mRS 0-1 (OR 1.39; 95% CI 1.20-1.60). IVT was associated with a higher probability of achieving excellent functional outcome in patients with NIHSS 4-5 (OR 1.53; 95% CI 1.06-2.21) and NIHSS 2-3 (OR 1.64; 95% CI 1.32-2.03), but not NIHSS 0-1 (OR 1.14; 95% CI 0.89-1.44). No significant differences in overall mortality were observed. SICH occurred in 3.7% of IVT-treated patients. IVT was associated with favorable functional outcomes for mild AIS, but not in patients with NIHSS 0-1.

To predict self-care and mobility function at discharge from inpatient rehabilitation for adults with stroke using only variables from the Inpatient Rehabilitation Facility Patient Assessment Instrument (IRF-PAI), which are mandated in the United States by the Centers for Medicare and Medicaid Services. Retrospective cohort study. Inpatient rehabilitation facilities (IRFs) in the United States. National sample (n=43,745) of adults with a primary diagnosis of stroke who were admitted to IRFs in FY2023. N/A MAIN OUTCOME MEASURES: Section GG self-care and mobility subscales. We used random forest regression, an ensemble machine learning approach that trains multiple models and combines their predictions to improve overall performance. We then created global summary trees from the random forest models to visually represent the outcome and aid in clinical interpretation. After data cleaning and quality checks, 39,870 records were available for analysis. Records were divided into training (n=26,580), validation (n=6,645), and test (n=6,645) datasets. Each model included 29 predictors. Random forest models explained 58% (RMSE=5.6) and 62% (RMSE=13.3) of the total variation in self-care and mobility outcomes, respectively, when applied to the test split. In both summary trees, the respective functional measure at admission was the strongest predictor. Bladder and bowel incontinence were strong predictors of both self-care and mobility outcomes at discharge. The results show that standard data elements from mandatory Medicare reporting can generate robust, clinically interpretable prediction models of self-care and mobility function at discharge from inpatient rehabilitation for adults with stroke. Application of such models in practice can inform treatment planning and early discharge preparation to support personalized rehabilitation approaches.

People after stroke lose accurate movement partly due to weakness, but this is compounded by poor sensory feedback. Furthermore, motivation and engagement can impact participation in rehabilitation. To address these barriers to recovery, a novel theatrical effects program called Proximity, which provided augmented visual feedback, was set up in a stroke inpatient rehabilitation ward with a cross-disciplinary team of dancers, designers and clinicians. The overall aim of the study was to evaluate the safety, feasibility and acceptability of the program, as well as to explore potential benefits. This exploratory feasibility study included 12 stroke and brain injury survivors and employed a mixed-methods, participatory action approach - collecting feasibility and acceptability data alongside semi-structured interviews, using an interpretive phenomenological analysis. Five different effects were adapted for Proximity: Clinical, comprising real-time screen displays with special effects to augment the life-size video images of the participants as they moved in front of the camera. Eleven of the 12 participants reported benefits, and this was supported by the observing clinicians. The theatre-based set-up was intensive and required considerable space. The effects enabled participants, firstly, to see for themselves what they were or were not doing in their postures and movements, and secondly, to immediately self-generate and evaluate changes in performance. In turn, this appeared to enhance agency, curiosity and enjoyment. This change in atmosphere - from remedial to creative exploration - was an unexpected but welcome experience for the cross-disciplinary team and reflects contemporary thinking in the arts/health nexus. The clinical arts-in-health program warrants further investigation using simplified equipment, under a combination of arts&#x2011;in&#x2011;health and clinical trial conditions.

Post-stroke spasticity may involve dynamic abnormalities that impair voluntary movement, such as muscle co-contraction during gait, which may be present even in patients without apparent spasticity at rest. This study aimed to identify brain lesion locations associated with abnormal lower-limb muscle co-contraction during walking using support vector regression lesion-symptom mapping. Thirty-two ambulatory patients with first-ever supratentorial stroke were included. Lower-limb motor impairment was defined as a Fugl-Meyer Assessment lower-extremity score of < 34. Surface electromyography recorded activity of the tibialis anterior and medial gastrocnemius muscles during gait. The co-activation index (CoI) was calculated from the overlap of normalized electromyography waveforms during the swing phase. Lesions were delineated on magnetic resonance imaging and analyzed using support vector regression lesion-symptom mapping, followed by disconnectome analysis to identify involved white matter tracts. A higher CoI was associated with lesions in the premotor cortex, precentral gyrus, and superior longitudinal fasciculus, with a 100% probability of disconnection in the second and third branches of the superior longitudinal fasciculus. Lesions in regions involved in sensorimotor integration were associated with abnormal lower-limb muscle co-contraction during walking, supporting the importance of dynamic gait assessment and targeted rehabilitation after stroke.

The contralesional dorsal premotor cortex (cPMd) is a potential target for motor recovery in severe stroke. However, interindividual heterogeneity and the limited efficacy of standalone repetitive transcranial magnetic stimulation may restrict its clinical benefit. This study aims to investigate whether cathodal high-definition transcranial direct current stimulation (HD-tDCS) preconditioning enhances the effects of intermittent theta-burst stimulation (iTBS) over the cPMd on upper limb function in patients with severe ischaemic stroke. This participant-blinded and outcome assessor-blinded, randomised controlled trial will enrol 90 patients with severe ischaemic stroke, defined as a Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score &#x2264;22. Participants will be randomly assigned in a 1:1:1 ratio to one of three groups: (1) the HD-tDCS+iTBS group, receiving cathodal HD-tDCS preconditioning over the cPMd followed by iTBS; (2) the sham HD-tDCS+iTBS group, receiving sham HD-tDCS preconditioning over the cPMd followed by iTBS; and (3) the sham HD-tDCS+sham&#x2009;iTBS group, receiving sham HD-tDCS preconditioning over the cPMd followed by sham iTBS. Cathodal HD-tDCS will be delivered at 1.5 mA for 20&#x2009;min and iTBS at 80% of the active motor threshold. Stimulation sessions will be administered once daily, 5&#x2009;days per week for four consecutive weeks. All participants will also receive conventional rehabilitation therapy during the intervention period. The primary outcome is the FMA-UE. Secondary outcomes include the Arm Subscore of the Motricity Index, the Hong Kong edition of the Functional Test for the Hemiplegic Upper Extremity, the Modified Barthel Index and the Modified Ashworth Scale. Functional MRI and diffusion tensor imaging will be performed. All clinical and imaging outcome measures will be evaluated at baseline and after the intervention. The study has been approved by the Ethics Committee of the First Affiliated Hospital with Nanjing Medical University (2025-SR-1066). The findings will be published in peer-reviewed journals and presented at international rehabilitation conferences. ChiCTR2600119646.

Complex High-risk Indicated Percutaneous Coronary Intervention (CHIP-PCI) addresses complex coronary artery disease in patients unsuitable for or declining surgery. Performing CHIP-PCI in non-surgical centres presents unique challenges requiring robust risk mitigation. CHIP-PCI was defined as PCI in any patient meeting at least one of the following criteria: PCI to left main stem, chronic total occlusion, severe coronary artery calcification (CAC), bifurcation lesions, left ventricular ejection fraction (LVEF) < 30%, serum creatinine > 200&#x3bc;mol/L, chronic dialysis, intra-aortic balloon pump use, previous coronary artery bypass graft, or age &#x2265; 80 years. Locally, the outcomes of major adverse cardiovascular events (MACE) - a composite of myocardial infarction, stroke, and cardiovascular mortality - and their associated factors after CHIP-PCI remain poorly understood. This study aims to evaluate 30-day MACE, patient characteristics and variables associated with mortality in CHIP-PCI. This single-centre retrospective cohort study with 30-day follow-up utilised anonymous secondary data from CHIP-PCI patients treated at the Department of Cardiology, Hospital Raja Permaisuri Bainun between 1st January and 31st December 2024. Data extracted included demographics, comorbidities, laboratory investigations (low-density lipoprotein [LDL], serum creatinine, echocardiography findings), and intra- and postprocedural findings. Patients with missing data for &#x2265; 3 variables of interest were excluded. A multivariate binary logistic regression analysis was conducted to identify the variables associated with mortality post CHIP-PCI. Of the 161 total patients, 146 (90.7%) were included in the analysis. Among these, 71.9% were male, and the mean age was 63.03 &#xb1; 10.19 years. Common comorbidities included hypertension (83.6%), diabetes mellitus (66.4%), elevated LDL (51.6%), serum creatinine > 200&#x3bc;mol/L (38.4%), prior Acute Coronary Syndrome (37.0%), chronic dialysis (30.1%), and LVEF < 30% (9.6%). Radial access was the most common approach (72.6%), and PCI was most frequently performed for severe CAC (46.6%). Intracoronary imaging was used in 43.8% of cases, and 39.0% required advanced calcium modification technique (atherectomy or intravascular lithotripsy). Most were single-lesion PCI (80.8%), with the left anterior descending artery (80.8%) being the most treated vessel. The 30-day MACE rate was 5.5% (4.8% mortality, 0.7% stroke, and 0% recurrent myocardial infarction). Multivariate analysis demonstrated that LVEF < 30% (AOR: 41.1, 95% CI: 1.1-1563.8, p = 0.04), severe CAC (AOR: 28.2, 95% CI: 1.3-619.3; p = 0.03), elevated LDL (AOR: 28.7, 95% CI: 1.2-701.1; p = 0.04), and readmission (AOR: 81.7, 95% CI: 4.1-1618.3, p < 0.001) were exploratory variables associated with 30-day mortality. This study demonstrates that the 30-day MACE rate for CHIP-PCI was 5.5%, suggesting the procedure may be feasible with acceptable short-term outcomes in a nonsurgical centre. Severely reduced LVEF, severe CAC, elevated LDL levels, and hospital re-admission showed potential associations with 30-day mortality highlighting the need for optimised strategies for patient risk mitigation.

Systemic inflammation contributes to cerebrovascular injury, yet cerebral small vessel disease and intracranial arterial calcification are typically evaluated separately. The aim of this study was to investigate the association between systemic inflammatory indices and the combined burden of small vessel disease and intracranial arterial calcification in acute ischemic stroke. This retrospective study included 166 patients with acute anterior circulation ischemic stroke. Total small vessel disease burden (white matter hyperintensities, lacunes, cerebral microbleeds, and enlarged perivascular spaces) was assessed on magnetic resonance imaging. Intracranial arterial calcification severity was evaluated on non-contrast computed tomography using a semiquantitative grading system. Inflammatory indices, including neutrophil-to-lymphocyte ratio and systemic inflammatory response index, were calculated from baseline blood samples. Multivariate regression analyses were performed to identify independent predictors. A total of 166 patients (mean age 64.5&#xb1;9.8 years) were included. In multivariate analysis, the neutrophil-to-lymphocyte ratio was an independent predictor of both total small vessel disease burden (&#x3b2;=0.39, p=0.026) and intracranial arterial calcification severity (&#x3b2;=0.181, p=0.030), whereas the systemic inflammatory response index was not significant after adjustment. Additionally, the neutrophil-to-lymphocyte ratio was independently associated with cerebral microbleeds and hypertension, and platelet-related indices were associated with infarct size and enlarged perivascular spaces. Neutrophil-to-lymphocyte ratio is independently associated with both microvascular and macrovascular cerebrovascular injury, supporting an inflammation-driven continuum. It may serve as a practical biomarker for assessing global cerebrovascular disease burden.

Ischemic stroke (IS) is a detrimental neurological disorder with limited clinical therapeutic options. The Astragalus-Safflower herb pair (AS) shows therapeutic effects against IS, but its mechanism remains unclear. Herein, this study combined cerebral untargeted metabolomics, mitochondrial ultrastructural observation and 16&#xa0;S rDNA gut microbiota profiling to systematically explore its neuroprotective mechanism. This study aimed to evaluate the efficacy of AS in alleviating IS, and investigate its mechanism of action. Rat models of middle cerebral artery occlusion (MCAO) were established using the intraluminal filament method. Behavioral tests confirmed that AS significantly improved neurological deficits and motor function. Untargeted metabolomics revealed that AS reversed nine IS-related energy metabolites in brain tissue. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicated involvement of nicotinamide metabolism and the TCA cycle. Molecular studies demonstrated that AS regulated mitochondrial energy metabolism via the AMPK/Sirt1/PGC-1&#x3b1; axis. Additionally, 16&#xa0;S rDNA sequencing showed that AS restructured gut microbiota composition. Correlation analysis suggested a gut-brain axis mechanism linking microbial changes to cerebral energy metabolism. In conclusion, AS exerts neuroprotection against IS by activating the AMPK/Sirt1/PGC-1&#x3b1; pathway, thereby enhancing TCA cycle activity and maintaining energy homeostasis. Concurrently, AS reshapes the gut microbiota, contributing to its effects via the gut-brain axis. Taken together, this integrated multi-omics study systematically clarifies the multi-target pharmacological characteristics of AS. These findings provide a novel multi-target mechanistic basis for the clinical application of AS in the treatment of IS and enrich the understanding of its synergistic neuroprotective mechanism.

Comparative data on tenecteplase versus alteplase in patients aged &#x2265;80 years undergoing bridging therapy before thrombectomy are limited. We retrospectively analyzed two prospective cohorts of patients aged &#x2265;80 years with anterior circulation large-vessel occlusion treated with bridging intravenous thrombolysis: the multicenter TETRIS registry (tenecteplase) and a single comprehensive stroke center (alteplase). Propensity score matching (1:1, 11 covariates, caliper 0.2 SD logit) was performed, with overlap weighting as sensitivity analysis; matched dichotomous outcomes were analyzed by conditional logistic regression and generalized estimating equations clustered on the matched pair. Because treatment was completely confounded with center and data source, analyses compare cohorts rather than isolate a drug effect. The primary outcome was modified Rankin Scale (mRS) &#x2264;3 at 90 days. Secondary outcomes included substantial early neurological improvement (ENI: &#x2265;8-point NIHSS improvement or NIHSS &#x2264;1 at 24 h), complete early neurological recovery (NIHSS = 0 at 24 h), early reperfusion (eTICI 2b-3), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. Among 720 eligible patients, 278 matched pairs were analyzed. The primary outcome (mRS &#x2264;3) occurred in 48.0% of tenecteplase- versus 43.5% of alteplase-treated patients (OR 1.20, 95% CI 0.86-1.67); an excellent outcome (mRS 0-2: 27.6% vs 27.0%), the ordinal mRS shift (common OR 1.06), early reperfusion (16.9% vs 16.5%), substantial ENI (40.2% vs 34.9%), sICH (3.7% vs 4.4%), and 90-day mortality (30.2% vs 30.2%) did not differ. Complete early neurological recovery (NIHSS = 0 at 24 h) was more frequent with tenecteplase (10.3% vs 2.6%; OR &#x2248;4.3), but this difference was confined to the single NIHSS value 0, reversed at NIHSS = 1, left no trace in any 90-day endpoint, and was nullified by modest unmeasured confounding (E-value for the lower confidence bound &#x2248;2-3). In patients aged &#x2265;80 years undergoing bridging therapy, tenecteplase and alteplase were associated with similar 90-day functional outcomes and similar safety. An isolated 24-hour complete-recovery signal favoring tenecteplase is hypothesis-generating and vulnerable to ascertainment bias, given complete confounding of treatment with center. Dedicated randomized data in this age group are warranted.

[This corrects the article DOI: 10.1097/MS9.0000000000003628.].

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