Journal of Stroke and Cerebrovascular Diseases

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a severe form of stroke associated with higher morbidity and mortality. Posterior circulation aneurysms are considered to have worse prognosis than anterior circulation aneurysms due to anatomical location, hemorrhage severity, and treatment complexity. We aimed to determine whether aneurysm location independently influences clinical outcomes following aSAH Methods: PubMed, Scopus, Embase, and Web of Science were searched from January 2000 to December 2025 for studies reporting outcomes in anterior or posterior circulation aSAH. The outcome analysis included mortality, functional recovery (modified Rankin Scale [mRS] 0-2 and 3-6 at 6 months and 1 year), hydrocephalus, delayed cerebral ischemia (DCI), and symptomatic cerebral vasospasm. Pooled proportions and subgroup comparisons were performed using random-effects meta-analysis (DerSimonian-Laird method). Publication bias was evaluated using contour-enhanced funnel plots and Egger's test. Results: Nineteen analytic entries from 18 studies (anterior: n = 1,625; posterior: n = 986; total N = 2,611) were included. Pooled mortality was 13% (95% CI: 10%-17%; I2 = 84.6%), with no significant difference between the anterior (14%; 95% CI: 10%-20%) and posterior (11%; 95% CI: 7%-18%) circulation subgroups (p = 0.437). Good functional outcome was 60% at 6 months (95% CI: 51%-67%) and 55% at 1 year (95% CI: 46%-64%), with no location-based differences. Hydrocephalus (35% vs 35%; p = 0.979) and DCI (17% vs 17%; p = 0.939) were comparable between subgroups. Symptomatic cerebral vasospasm was the only outcome differing significantly by location, occurring more frequently in anterior circulation aSAH (24% vs 11%; {chi}2 = 5.59; p = 0.018). Conclusion: Aneurysm location does not independently determine mortality, functional recovery, hydrocephalus, or DCI following aSAH. Symptomatic cerebral vasospasm was the only location-specific outcome. Admission neurological grade (World Federation of Neurosurgical Societies [WFNS]), rather than vascular territory, appears to be the primary determinant of mortality. Aneurysm location alone should not guide prognostic decisions or limit aggressive treatment.

Objective: To assess ethnic disparities in time to hospital presentation, use of acute reperfusion therapies, and in-hospital treatment times among patients presenting with stroke in a Dutch emergency department. Methods: In this single-centre observational cohort study, we included patients with a first-ever ischemic stroke between September 2020 and September 2021. Patients were categorized by ethnicity (with or without migration background). Demographic and stroke characteristics were compared between groups. Outcomes included: rates of presentation outside therapeutic time window, acute reperfusion therapy (intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)), and, when applicable, door-to-treatment time (DTTT), with a door-to-needle time (DTNT) and door-to-groin time (DTGT) for IVT and EVT respectively. Univariable and multivariable linear and logistic regression analyses were performed, adjusted for age, sex, and NIHSS at presentation, where appropriate. Results: A total of 232 patients were included, of whom 62 (26.7%) had a migration background. These patients were younger (66.6 vs 71.2 years) and more frequently had diabetes (27.4% vs 15.9%). Sex distribution was similar (59.7% vs 60.6% male). Stroke etiology differed between groups with less cardio-embolism (4.8% vs 15.3%) and more small vessel disease (69.4% vs 48.2%) among patients with a migration background. These latter patients presented more often outside the therapeutic time window (53.2% vs 37.1%; OR 1.90; 95% CI 1.05-3.45). EVT was less frequently performed in patients with a migration background compared to those without (8.1% vs 22.4%; OR 0.28; 95% CI 0.10-0.75). There were no significant differences in treatment times (DTTT 38min vs 30min, DTNT 35min vs 26min, DTGT 64min vs 54min). Conclusion: Patients with a migration background were more likely to present outside the therapeutic time window and had a lower rate of EVT. In order to improve access for these patients, more insight into prehospital and within hospital barriers and facilitators for appropriate management are needed.

Sex specific differences in stroke are recognized. Whether differences in incident stroke risk persists in recent periods needs further elucidation to aid public health preventive efforts. Aim: To determine long-term sex specific trends in stroke and stroke risk factors at different epochs among Framingham Heart Study participants. Methods: We examined age-adjusted 10-year stroke incidence using Cox regression in women and men in five epochs: 1962-1969 (epoch 1, reference), 1971-1976 (epoch 2), 1987-1991 (epoch 3), 1998-2005 (epoch 4), 2015-2021 (epoch 5). We compared stroke incidence by sex across epochs, estimated decade-wise linear trends overall and by sex. We compared risk factors in successive epochs to the first, and estimated sex-specific trends in risk factors. Interactions between baseline risk factors with epoch and trends were assessed by sex. Secondary analyses were repeated in participants <60 years old. Results: Incident stroke occurred in 4.5% (178/3996) in epoch 1, 3.9% (227/5786) in epoch 2, 3.9% (199/5137) in epoch 3, 2.7% (207/7642) in epoch 4, 2.2% (119/5534) in epoch 5. Men had higher risk of incident stroke in each epoch with significant difference in epochs 2 (HR 1.41, 95% CI [1.08, 1.84]) and 4 (HR 1.46, 95% CI [1.11, 1.91]) overall, and in epoch 4 (HR 2.13, 95% CI [1.17, 3.87]) among those <60 years. Stroke incidence declined by 16% per decade in men (HR 0.84, 95% CI [0.79, 0.89]) and 19% per decade in women (HR 0.81, 95% CI [0.76, 0.86]). Among those <60 years, stroke incidence declined by 22% per decade in women (HR 0.78, 95% CI [0.67, 0.95]). Hypertension declined by 8% per decade in women only ([OR] 0.92, 95% CI [0.90, 0.94]), while Atrial fibrillation and diabetes increased in both. Conclusion: Stroke incidence continues to decline in recent periods for women and men. Among participants <60 years, decline was observed only in women, possibly related to decline in hypertension in women.

Abstract Objective: To compare the safety and efficacy of bridging intravenous thrombolysis (IVT) plus endovascular thrombectomy (EVT) versus direct EVT in patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO) treated within the 6- to 24-hour time window. Methods: This is a retrospective analysis of prospective EVT registry from 10 comprehensive stroke centers in China and Singapore between 2019 and 2024. Eligible patients had anterior circulation LVO, underwent EVT within 6-24 hours of onset, had ASPECTS 6, NIHSS 6, and pre-stroke mRS 2. Patients were stratified into bridging IVT + EVT (IVT group) versus direct EVT alone (non-IVT group). Propensity score matching (1:2 ratio) was performed to balance baseline covariates. The primary outcome was 3-month favorable functional outcome (mRS 0-2). Secondary outcomes included successful recanalization (mTICI 2b-3), symptomatic intracranial hemorrhage (sICH), hemorrhagic transformation (HT) and 3-month mortality. In the matched cohort, binary outcomes were compared using the Cochran-Mantel-Haenszel test. Results: Of 772 included patients, 110 (14.2%) received bridging IVT and 662 (85.8%) received direct EVT. After propensity score matching, 202 non-IVT patients were matched to 101 IVT patients, with all covariates well-balanced (absolute SMD <0.10). In the matched cohort, bridging IVT was not associated with a significant difference in 3-month favorable outcome (44.55% vs. 47.03%; common OR 0.91; 95% CI 0.56-1.46), successful recanalization (91.09% vs. 90.10%; OR 1.11; 0.51-2.44), sICH (5.94% vs. 9.41%; OR 0.61; 0.24-1.58), HT (23.76% vs. 23.27%; OR 1.03; 0.57-1.85), or 3-month mortality (15.84% vs. 13.37%; OR 1.22; 0.62-2.37). Conclusion: In this large multicenter propensity score-matched analysis, bridging intravenous thrombolysis before endovascular thrombectomy in the 6- to 24-hour time window was not significantly associated with improved efficacy or increased safety risks compared with direct endovascular therapy alone.

Background: Poor physical performance, measured by gait speed and chair stands, is associated with mortality; associations may differ by history of cardiovascular disease (CVD). Methods: Among 14,137 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants, gait speed and chair stand times (2013-2016) were categorized into quartiles and a fifth category with those who were unable to complete the test. Associations with adjudicated CVD and all-cause mortality through 2020 were examined among participants with and without history of CVD. Results: Average age was 72.5 {+/-} 8.5 years. Among participants without history of CVD, those in slowest vs. highest gait speed quartile had HRs of 2.01 (95% CI 1.18-3.43) for CVD and 1.66 (1.33-2.07) for all-cause mortality; among those unable to complete the test, HRs were 2.37 (1.12-5.03) for CVD and 2.33 (1.72-3.17) for all-cause mortality. Among participants with history of CVD, slowest gait speed quartile had HRs of 1.28 (0.96-1.72) for CVD and 1.72 (1.45-2.04) for all-cause mortality; HR among those unable to complete the test were 1.87 (1.29-2.70) for CVD and 2.74 (2.22-3.38) for all-cause mortality (p-interaction between with and without history of CVD <0.05). Inability to complete chair stand test was associated with higher mortality in both groups. Conclusions: Poor physical performance was associated with greater CVD-related and all-cause mortality among both individuals with and without a history of CVD, with the highest risks observed among those who were unable to the assessments.

Bakground and Purpose Antiplatelet resistance is a recognized risk factor for recurrent ischemic stroke, yet evidence supporting platelet function test?guided antiplatelet therapy modification in stroke prevention remains limited. We investigated whether VerifyNow-guided antiplatelet therapy modification reduces recurrent ischemic stroke in patients with atherothrombotic or lacunar infarction. Methods This retrospective observational study enrolled consecutive patients with atherothrombotic or lacunar infarction at a single center (April 2023-March 2025). Of 302 patients, 243 were analyzed: 122 in the modified group, whose antiplatelet agent was selected based on VerifyNow Aspirin Reaction Units and P2Y12 Reaction Units, and 121 in the unmodified group, whose agent was empirically selected. The mean follow-up period was 1.62 {+/-} 0.61 years. In the modified group, when both aspirin and clopidogrel showed inadequate inhibition, prasugrel or cilostazol was selected. The primary endpoint was recurrent ischemic stroke; the secondary endpoint was intracranial hemorrhage. Cox proportional hazards models with inverse probability weighting were used to adjust for confounders. Results Recurrent ischemic stroke occurred in 1 patient (0.8%) in the modified group versus 8 (6.6%) in the unmodified group (log-rank P=0.018). After adjustment, the modified group had a significantly lower risk of recurrent stroke (HR, 0.10; 95% CI, 0.012-0.84; P=0.033). Intracranial hemorrhage occurred in 0 (0%) and 1 (0.8%) patients, respectively. Conclusions In Japanese patients with atherothrombotic or lacunar infarction, VerifyNow-guided antiplatelet therapy modification was associated with a significantly lower incidence of recurrent ischemic stroke without increased hemorrhagic risk. Given the single-center retrospective design and small sample size, validation in a multicenter randomized controlled trial is warranted.

Background Venous thromboembolism (VTE) remains a major cause of perioperative morbidity in cranial neurosurgery, yet clinical practice varies widely, and formal guidelines are inconsistent. Understanding internationally sampled neurosurgical practice is essential for informing consensus and future trials. Methods An international, 2-stage cross-sectional, internet-based survey was conducted. Practising neurosurgeons performing elective adult cranial surgery were eligible. Descriptive statistics were used to summarise practice. Responses covered patterns of pre-operative haemostasis decision making, use and timing of mechanical and/or chemical prophylaxis, use of perioperative imaging prior to anticoagulation, and frequency of clinical assessment for VTE. Associations with geographical income status, subspecialty, and years post-certification were statistically tested. Practice heterogeneity was quantified and contextual influence was summarised using mean effect sizes across stratifying variables in order to determine domains of true equipoise. Results Of 585 responses, 456 (78%) met criteria for inclusion: representing 322 units across 78 countries (71% high-income). Thirteen per cent reported no departmental VTE plan; 23% followed no guidelines and 12% used multiple. Routine pre-operative testing almost universally included haemoglobin/platelets/haematocrit, with fibrinogen more common in high-income settings. Compared with high-income country respondents, low- and middle-income respondents reported higher haemoglobin transfusion thresholds (>90 g/dL; p<0.001) and shorter antiplatelet interruption (p[&le;]0.03), and less frequent outpatient VTE assessment (p<0.001). Mechanical prophylaxis was common (TEDs 81%, IPC 62%), typically started pre- or intra-operatively. Among those completing the chemoprophylaxis section (n=310), 57% required a CT or MRI scan before LMWH which was then initiated on average 31.4 hours after surgery. 1% of respondents did not routinely use LMWH. Many clinical decisions demonstrated statistical equipoise ie. high heterogeneity with low contextual influence. Conclusion Peri-operative haemostasis and VTE prophylaxis practices in adult elective cranial neurosurgery vary substantially worldwide, with some decisions reflecting geographical or socioeconomic differences and many others reflecting true clinical equipoise rather than contextual determinants. By mapping contemporary real-world practice across diverse health-system contexts, this study provides a necessary empirical foundation for rational trial design and future guideline development.

Background: Previous studies have shown the benefit of dual antiplatelet therapy (DAPT) for acute minor ischemic stroke. Argatroban, is a thrombin inhibitor and is primarily used in patients with acute ischemic stroke experiencing early neurological deterioration. There is no study about the benefit of antiplatelet plus anticoagulant in this population. We aim to study the difference between the combination of argatroban and clopidogrel and DAPT in the outcomes of patients with acute minor ischemic stroke (AMIS, NIHSS <5) presenting within 72 hours after onset. Methods: Argatroban combined with clopidogrel versus aspirin combined with clopidogrel in Stroke (ACAP study) is an investigator-initiated, multicenter, prospective, randomized, open-label trial with blinded endpoint evaluation conducted at four centers in China. This trial will randomize 464 eligible patients with minor ischemic stroke of NIHSS 5 (232 in each arm) within 72 hours of the last known well to receive intravenous argatroban with clopidogrel (treatment group) or aspirin plus clopidogrel (control group). The primary outcome is the proportion of patients achieving excellent outcome, defined as a score of 0-1 on the modified Rankin scale, at 90 days. Conclusions: The ACAP trial will provide important data on the role of intravenous argatroban in patients with acute minor ischemic stroke presenting within 72 hours of last known well.

Abstract Background: Acute ischemic stroke (AIS) remains a significant cause of disability worldwide. Current treatments, primarily intravenous thrombolysis (IVT), are limited by narrow time windows and reperfusion injury, leading to suboptimal outcomes for many patients. Chuanzhi Tongluo (CZTL), a traditional Chinese medicine, has been preliminarily recognized as a novel cerebral protection agent in animal models. Objectives: This trial investigates the efficacy and safety of CZTL capsule in patients with AIS who are not eligible for IVT or who experience early neurological deterioration after IVT. Methods and design: The CONCERN trial is an investigator-initiated, prospective, multicenter, double-blind, parallel-control, randomized clinical study in China. An estimated 1,208 eligible participants will be consecutively randomized to receive CZTL capsule therapy or placebo in 1:1 ratio across approximately 70 stroke centers in China. All enrolled patients are orally administered 2 capsules of CZTL or placebo 3 times a day together with antiplatelet agents for 3 months. Outcomes: The primary endpoint is an excellent functional outcome, defined as a score of 0 or 1 on the mRS at 90 days. Lead safety endpoints included 90-day mortality and symptomatic intracranial hemorrhage within 48 hours. Conclusions: Results of CONCERN trial will determine the clinical efficacy and safety of the traditional Chinese medicine CZTL capsule in the treatment of AIS patients. Trial registry number: ChiCTR2300074147 (www.chictr.org.cn).

BackgroundGlobal cerebral anoxia is a leading cause of death and resuscitated patients often remained persistently affected by neurological deficits. While previous studies suggest that brain-heart electrophysiological interactions may predict severity and prognosis after hypoxic brain injury coma, little is known about the brain-heart dynamics at near-death. Gaining insight into these mechanisms is crucial for developing targeted interventions in critical conditions. ResultsUsing a rodent model of reversible systemic anoxia (n=29, male and female rats), we investigated whether brain-heart interactions during the asphyxia onset could predict the return of brain electrical activities after resuscitation. Electrophysiological recordings confirmed that cerebral activity declines following asphyxia, coinciding with increased heart rate variability. Notably, the strong coupling between cardiac parasympathetic activity and high-frequency brain activity in the somatosensory cortex and hippocampus serves as a key predictor of a favorable outcome. ConclusionOur study underscores the involvement of the brain-heart axis mechanisms in the physiology of dying and the potential prognostic significance of these mechanisms, paving the way for translational research into critical care, based on new characterizations of cardiac reflexes and brain-heart interactions.

Background: Clinical evidence on the contemporary management and functional outcomes of patients with Wernicke encephalopathy remains limited. This study aimed to clarify the nationwide patterns of thiamine administration and functional outcomes at discharge. Methods: Using the Japanese nationwide inpatient Diagnosis Procedure Combination database, we identified patients hospitalized with Wernicke encephalopathy between July 2010 and March 2024. Initial intravenous thiamine doses were categorized as low ([&le;]300 mg/day), medium (301-900 mg/day), or high (>900 mg/day). Outcomes included in-hospital mortality and functional status (Barthel Index) at discharge. Results: We identified 7856 patients with Wernicke encephalopathy. Over the 13-year study period, the proportion of patients receiving initial high-dose thiamine increased markedly from 5.4% to 49.0%, while the frequency of low-dose therapy decreased from 83.0% to 37.9%. Despite prompt intervention [median time to initial administration: 0 days (interquartile range, 0 to 0 days)], 56.1% of patients were discharged with impaired activities of daily living (Barthel Index <90), and the in-hospital mortality rate was 3.8%. Conclusions: High-dose thiamine treatment is increasingly implemented for Wernicke encephalopathy in Japan. Although in-hospital mortality was relatively low, the high prevalence of functional impairment at discharge, despite early treatment initiation, indicates substantial burden of Wernicke encephalopathy. Given the limited clinical evidence, further research investigating the optimal thiamine dose and develop effective primary prevention strategies for Wernicke encephalopathy is needed.

BackgroundNeurodevelopmental impairment remains common in neonatal hypoxic-ischemic encephalopathy (HIE) despite treatment with the standard of care, therapeutic hypothermia (TH). The complement response activates at reperfusion and is known to exacerbate neuroinflammation and injury, though its full role and interaction with hypothermia are incompletely defined. We hypothesized that modulating the complement response could improve structural and functional outcomes in HIE, and tested a novel complement therapy (CT), consisting of C3a peptides and the C5a-receptor antagonist PMX205, as both a stand-alone treatment and as an adjuvant to TH. MethodsWistar rat pups were randomized to the following treatment groups: Sham (uninjured control), NT (uninjured, normothermia/not treated control), or injured and treated with either TH, CT, or CT+TH. At term-equivalence, mild-moderate hypoxic-ischemic injury was induced by Vannuccis method. To capture the short and long-term effects of the treatments, cohorts were harvested 3 or 66-72 days post-injury, respectively. Cerebral injury was measured by quantifying levels of inflammatory markers and cerebral tissue loss, and functional outcomes were assessed in a series of behavioral tests. The data were stratified to detect sexual dimorphisms. ResultsCT and TH treatments demonstrated test and sex-dependent differences in improvement compared to untreated, injured rats. In male rats, TH treatment worsened long-term hippocampal and thalamic brain injury and functional measures of ataxia and attention. CT-treatment worsened long-term thalamic loss in females. Combining the two treatments (CT+TH) demonstrated additive improvement in both sexes, including short and long-term cortical loss and ataxia. ConclusionsComplement modulation enhances the neuroprotective effects of TH after neonatal hypoxic-ischemic injury, with sex-specific effects on inflammation and behavior. Combining complement modulation with the standard of care often demonstrated synergistic improvement in both sexes, supporting complement-targeted therapy as a promising adjunct to hypothermia in neonatal HIE. Graphical abstract. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/717097v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@1025d1forg.highwire.dtl.DTLVardef@2fa4e5org.highwire.dtl.DTLVardef@1f2c1c4org.highwire.dtl.DTLVardef@8f3410_HPS_FORMAT_FIGEXP M_FIG C_FIG Created with BioRender. Saadat, A. (2026) https://BioRender.com/siwm825.

STRUCTERED ABSTRACTO_ST_ABSBACKGROUNDC_ST_ABSCoronary artery bypass graft (CABG) is a widely performed procedure for coronary artery disease (CAD), yet its association with Impaired Cognition (IC), i.e., mild-cognitive impairment or all-cause dementia, while accounting for APO ({varepsilon}) genotype, remains unclear. METHODSWe analyzed AllofUS participants with CAD (Age[&ge;]60 yrs) from 2017-2023. We defined CAD as a history of angina/myocardial infarction/chronic ischemic heart disease or having percutaneous coronary intervention/CABG, and IC as mild cognitive impairment or all-cause dementia using ICD/SNOMED codes. We performed logistic regression analyses to assess the association between CABG and IC, adjusting for clinical factors (age, sex, hypertension, diabetes, hyperlipidemia, depression, stroke, smoking, alcohol use, statin/antihypertensive/antidiabetic use), social determinants (self-reported race/ethnicity, income, employment), and APO ({varepsilon}) genotypes. We further performed stratified analyses across APO ({varepsilon}) genotypes ({varepsilon}2/{varepsilon}2, {varepsilon}2/{varepsilon}3 {varepsilon}3/{varepsilon}3, {varepsilon}2/{varepsilon}4, {varepsilon}3/{varepsilon}4, {varepsilon}4/{varepsilon}4). We defined significance at p [&le;] 0.05. RESULTSWe included 22,349 with CAD and identified 908 with IC after CAD till 2023. 40% were females, 70% were White, 12% were Black, and 9% were Hispanic. The proportion of IC was higher (5.1% vs 3.5%, p=1e-08) in CABG (n=8,135) vs non-CABG (n=14,214). After adjusting for clinical factors, social determinants, and APO ({varepsilon}) genotypes, CABG (1.23;1.06-1.41, p = 0.005) was associated with IC. In APO ({varepsilon}) stratified analysis, the association of CABG with IC was strongest in the APO {varepsilon}2/{varepsilon}3 group (1.91;1.21-3.02, p = 0.005). CONCLUSIONIn the AllofUS cohort, we observed an association between CABG and IC in CAD participants, with the strongest association in the APO {varepsilon}2/{varepsilon}3 group. Key MessageO_ST_ABSWhat is already known on this topicC_ST_ABSCoronary artery disease (CAD) and Impaired Cognitive (IC) disease, i.e., mild cognitive impairment and all-cause dementia, share genetic, sociodemographic, and clinical factors, including cardiovascular conditions like coronary artery bypass grafting (CABG) procedure. What this study addsWe observed an association between CABG and IC in CAD participants after adjusting for sociodemographic, clinical factors, and APO ({varepsilon}) effects. Further, when CAD participants were stratified across APO ({varepsilon}) groups, CABG was significantly associated with IC in the APO {varepsilon}2/{varepsilon}3 group. How this study might affect research, practice or policyOur observations highlight the role of APO ({varepsilon}) genotype evaluation in CAD patients for IC risk assessment.

ObjectiveLevetiracetam is commonly prescribed for seizure prophylaxis after acute ischemic stroke (AIS) and often continued beyond discharge. While its short-term effectiveness for preventing post-stroke seizures is established, it is unclear whether prolonged use improves survival, particularly in older adults. We estimated the effect of continued levetiracetam use on 90-day mortality among Medicare beneficiaries after AIS. MethodsUsing Traditional Medicare claims data (2008-2021), we identified beneficiaries aged [&ge;]66 years hospitalized for AIS who initiated outpatient levetiracetam within 90 days of discharge. After one month of continued post-stroke use of levetiracetam (start of follow-up), we compared 90-day mortality between patients with a new levetiracetam dispensation within a 14-day grace period post-follow up and those without one. We performed cloning, censoring and weighting to address immortal time bias and estimated standardized mortality risks, risk differences, and 95% confidence intervals (CI). ResultsAmong 3,212 eligible beneficiaries, 1,779 (55.4%) received a new levetiracetam dispensation within the 14-day grace period. Median age was 76 years (IQR 70-83); 57.8% were female. After adjustment for demographics, hospitalization characteristics, timing of initiation, and comorbidities, continued use was associated with lower 90-day mortality than discontinuation (53 vs 62 deaths per 1,000; risk difference -9 per 1,000; 95% CI: (-12,-5)). The reduction was observed primarily among patients aged [&ge;]75 years. SignificanceAmong older Medicare beneficiaries who initiated levetiracetam after AIS, continued outpatient use was associated with modestly lower 90-day mortality, particularly in those aged [&ge;]75 years. These findings suggest potential benefits of levetiracetam continuation beyond the immediate post-stroke period.

Abstract Background: ST-elevation myocardial infarction (STEMI) is reported to be a leading cause of mortality worldwide. While cardiac troponins are the gold standard for myocardial injury detection but creatine kinase-MB (CK-MB) and total creatine phosphokinase (CPK) retain prognostic use in resource-limited settings. Objective: To evaluate the prognostic significance of admission CK-MB and CPK levels in STEMI patients and to assess their association with hematological parameters for integrated risk stratification. Methods: This cross-sectional study enrolled 15 consecutive STEMI patients from the Punjab Institute of Cardiology, Lahore, during January 2024. Comprehensive laboratory analysis including cardiac biomarkers (CK-MB, CPK, troponin-I, LDH), complete blood count, renal function, serum electrolytes, and metabolic parameters, was performed on admission. Pearson correlation and comparative statistical analyses were also conducted to assess the relationships between cardiac biomarkers and hematological indices. Results: The cohort includes 15 patients (mean age 50.1 +/- 12.2 years; 73.3% male). Cardiac biomarker elevation was prevalent: CK-MB was elevated in 12/15 (80%), CPK was elevated in 12/15 (80%), with concordant elevation in 11/15 (73.3%), which indicates extensive myocardial necrosis. Troponin-I showed the highest elevation rate at 13/15 (86.7%). Hematological abnormalities included anemia (60%), WBC elevation (53.3%), and RBC reduction (40%). Random glucose averaged 150.80 +/- 63.55 mg/dL, with 66.7% highlighted the hyperglycemia. Remarkably, electrolyte balance was preserved in all of the patients (0% sodium, potassium, and bicarbonate abnormalities), indicating maintained homeostasis. Pearson correlation analysis revealed a significant correlation between CK-MB and CPK (r = 0.615, p = 0.0126), while correlations between cardiac biomarkers and hematological parameters were weak (p > 0.05). Risk stratification identified 53.3% of patients as high-risk who required intensive management. Conclusions: CK-MB and CPK demonstrate significant concordance and retain prognostic value in STEMI patients, particularly in resource-limited settings where troponin access may be constrained. While troponin-I remains the most sensitive biomarker, combined assessment of conventional cardiac enzymes supports reliable evaluation of myocardial injury. Hematological parameters reflect systemic response but show limited correlation with cardiac biomarkers.

Background: Prognostication after moderate-to-severe traumatic brain injury (TBI) rarely captures long-term functional recovery, despite its importance to patients, families, and clinicians. Large trauma registries such as the Trauma Quality Improvement Program (TQIP) dataset contain detailed clinical data but lack systematic follow-up, limiting their ability to study longer-term functional outcomes. Methods: We developed and externally validated a machine learning model to predict favorable six-month functional outcome (GOS MD/GR or GOSE >=5) using harmonized data from two randomized clinical trials: CRASH (training) and ROC-TBI (validation). Five candidate classifiers (random forest [RF], linear discriminant analysis, k-nearest neighbors, naive Bayes, and support vector machine) were trained using seven shared clinical predictors. Models were evaluated using ROC-AUC, calibration metrics, and performance at the Youden optimal threshold and a high-sensitivity secondary threshold. The final model was applied to patients with moderate-to-severe TBI in the national TQIP registry (2017-2022) to estimate population-level recovery patterns. Results: The RF model demonstrated the highest overall performance after recalibration, achieving strong discrimination (AUC internal and external, 0.887 and 0.784), good calibration, and high sensitivity (0.890) and negative predictive value (0.909). Applied to 63,289 patients from TQIP, the model estimated that 45% would achieve favorable six-month outcomes at the Youden optimal threshold and 57% at the high-sensitivity threshold, with predicted recovery aligning with established clinical correlates such as younger age, higher admission GCS, and lower rates of penetrating or brainstem injuries. Conclusion: A machine learning model trained on high-quality trial data can generate clinically plausible estimates of long-term functional recovery when applied at scale to national trauma registries that lack systematic follow-up. This approach enables imputation of functional outcomes in datasets lacking follow-up, supports benchmarking and quality improvement across trauma systems, and provides a foundation for future models incorporating physiologic time-series, imaging, and biomarker data.

Background: Intracranial atherosclerosis is a major cause of ischemic stroke. Asymptomatic intracranial atherosclerotic stenosis (ICAS) represents a subclinical and potentially modifiable stage preceding ischemic stroke, yet the nutritional factors associated with asymptomatic ICAS remain poorly defined. This study aimed to identify dietary factors associated with asymptomatic ICAS in community-dwelling older adults. Methods: This cross-sectional, population-based study included 962 Japanese adults aged {greater than or equal to}65 years from the Yahaba Active Aging and Healthy Brain study, conducted in Yahaba town, Japan, between July 2016 and July 2017. Asymptomatic ICAS was defined as {greater than or equal to}50% intracranial arterial stenosis evaluated by magnetic resonance angiography (MRA) without a history of stroke or transient ischemic attack. All participants underwent dietary assessment using a food frequency questionnaire. We examined the association between nutritional factors and ICAS using multivariable logistic regression models with adjustment for age, sex, hypertension, dyslipidemia, diabetes mellitus, body mass index, smoking, and alcohol use. Results: After exclusions, 850 participants were analyzed. The mean age was 73.4 {plus minus} 6.5 years, and 52% were female. ICAS was identified in 135 participants (15.9%). Participants in the highest quartile of dietary fiber intake had lower odds of ICAS than those in the lowest quartile (OR, 0.45; 95% CI, 0.26-0.80). Potassium intake showed a similar inverse association (OR, 0.49; 95% CI, 0.27-0.89). When both nutrients were included in the multivariable model as continuous variables, neither remained significant, with moderate collinearity (variance inflation factor, 4.16). Conclusions: Higher dietary fiber intake was inversely associated with asymptomatic ICAS among community-dwelling older Japanese adults. Potassium intake also showed an inverse association, although this relationship was less consistent after accounting for collinearity with dietary fiber.

Background: Many patients in the ICU receive oxygen to secure blood and tissue oxygenation. Increasing evidence shows exposure to high fractions of inhaled oxygen (FiO2) being associated with adverse effects. In patients with severe ARDS, veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) can be implemented as a rescue therapy and PaO2 levels can be controlled by the blood flow of the VV-ECMO. Yet, optimal oxygenation targets in ARDS patients treated with VV-ECMO are unknown. Methods: Retrospective analysis of 443 patients with severe ARDS treated with VV-ECMO. Regression analyses were performed for mortality and time-weighted averages of PaO2 and FiO2. Furthermore, considering a possible non-linear relationship, a restricted cubic spline (RCS) model was performed for PaO2. Results: A simple logistic regression for mean PaO2 and ICU mortality showed a significant positive association (per mmHg OR 0.99 [95%CI 0.98-1.00], p=0.002). RCS analysis showed a U-shaped association of mortality and mean paO2 (paO2 69.70-90.24mmHg: OR 0.92 [95%CI 0.89-0.94], p<0.001; paO2 90.24-123.40mmHg: OR 1.09 [95%CI 1.06-1.13], p<0.001). A model including PaO2 as RCS variable and FiO2 showed significant associations of mortality with both variables (PaO2 69.70-90.24mmHg: OR 0.94 [95%CI 0.91-0.97], p<0.001; paO2 90.24-123.40 mmHg: OR 1.07 [95%CI 1.04-1.11], p<0.001; FiO2: OR 35.98 [95%CI 8.67-158.60], p<0.001, VIF<1.11). Conclusions: PaO2-levels in patients with ARDS and VV-ECMO have a U-shaped association with mortality. Optimal outcomes are observed in the 90-123 mmHg range, which is higher compared to non-ECMO settings. Whether this is explainable by increased tissue oxygenation with concurrent avoidance of pulmonary hypoxia should be subject of future research.

Modelling of hemodynamics in the circle of Willis (CoW) depends on vascular segmentation, which may vary based on imaging modality. Computed tomography angiography (CTA) is commonly used in clinic but involves radiation and injection of contrast agents, whereas magnetic resonance angiography (MRA) offers a non-invasive alternative. This study aims to compare CoW morphology and modelled cerebral perfusion pressure of CTA and MRA segmentations, validating if MRA can replace CTA in modelling workflows. CTA and time-of-flight MRA (TOF-MRA) of the CoW was performed in 19 patients undergoing elective aortic arch surgery (67{+/-}7 years, 8 women). The CoW was semi-automatically segmented based on signal intensity thresholding. A TOF-MRA threshold was optimized against the CTA segmentation, using the CTA as reference standard. Computational fluid dynamics (CFD) modelling with boundary conditions based on subject-specific flow rates from 4D flow MRI simulated cerebral perfusion pressure in the segmented geometries. A baseline simulation and a unilateral brain inflow simulation, i.e., occlusion of a carotid, were carried out. Linear mixed models indicated there was no effect of choice of modality on either average arterial lumen area (CTA - TOF-MRA: -0.2{+/-}1.3 mm2; p=0.762) or baseline pressure drops (0.2{+/-}1.9 mmHg; p=0.257). In the unilateral inflow simulation, we found no difference in pressure laterality (-6.6{+/-}18.4 mmHg; p=0.185) or collateral flow rate (10{+/-}46 ml/min; p=0.421). TOF-MRA geometries can with signal intensity thresholding be matched to produce similar morphology and modelled cerebral perfusion pressure to CTA geometries. The modelled pressure drops over the collateral arteries were sensitive to the segmentation regardless of modality.

Introduction Despite the proven benefits of reperfusion therapies in acute ischemic stroke, treatment decisions in the hyperacute phase remain complex and are rarely supported by individualized outcome predictions. Artificial intelligence (AI)-based clinical decision support systems (CDSS) offer potential real-time prognostic estimates, but prospective evidence of their feasibility and performance in routine clinical workflows is limited. Our aim is to prospectively evaluate real-time feasibility, usability, and predictive performance of an AI-based CDSS (VALIDATE-CDSS) for individualized outcome prediction in acute stroke care. Methods and analysis Prospective, multicenter, observational study enrolling consecutive patients with acute ischemic stroke presenting to three tertiary stroke centers. Clinical management will follow standard practice at the discretion of treating physicians. In parallel, a dedicated researcher will collect patient data in real time and input them into the VALIDATE-CDSS using a mobile application, operating in shadow mode without influencing clinical decisions. The system will generate individualized predictions of 3-month functional outcome (modified Rankin Scale) for four treatment strategies (intravenous thrombolysis, endovascular thrombectomy, combined therapy, or no reperfusion) at three sequential time points: baseline clinical data, non-contrast CT, and CT angiography. The primary outcome is the real-world feasibility and usability of the VALIDATE-CDSS in the hyperacute stroke workflow. Secondary outcomes include predictive performance, agreement between model-suggested and actual treatments, incremental value with increasing data availability, and assessment of potential bias across predefined subgroups. This study will provide prospective real-world evidence on the implementation and clinical potential of AI-based decision support for personalized treatment selection in acute ischemic stroke Ethics and dissemination Patient enrollment began after approval from the ethics committees of all participating centers. Results will be disseminated through peer-reviewed open-access journals and conference presentations. Following open science principles, anonymized data and metadata will be made publicly available in the Zenodo repository upon study completion. Trial registration: ClinicalTrials.gov (NCT05622539).