Journal of Stroke and Cerebrovascular Diseases

BackgroundtPA is used for the acute treatment of ischaemic stroke because it converts plasminogen to active plasmin, which breaks down clots. Previous studies show that tPA-activated plasminogen impairs brain endothelial barrier function. However, it is unclear whether the plasmin product of this reaction directly contributes to brain endothelial barrier deterioration. ObjectiveDetermine whether plasmin directly influences the human brain endothelial barrier. MethodsWe developed a new serum-free hCMEC/D3 culture model with ECIS real-time monitoring to establish how plasmin in isolation influences the brain endothelial barrier. ResultsECIS monitoring demonstrated that plasmin caused a concentration-dependent decline in hCMEC/D3 barrier integrity, which was primarily mediated by a reduction in endothelial cell-to-cell interactions. Whilst a decrease in membrane capacitance and increase in basolateral adhesion were also observed, these changes were less marked. The inclusion of 2-antiplasmin ameliorated the changes in hCMEC/D3 barrier properties, suggesting this response is mediated by plasmins proteolytic activity. Quantitative immunocytochemistry confirmed that plasmin stimulated a decline in the key junctional molecules, Claudin-5, VE-Cadherin (CD144), {beta}-Catenin, ZO-1 and PECAM-1 (CD31), which likely contributed to the deterioration of paracellular cell-to-cell interactions. Interestingly, using this serum-free model, tPA alone didnt influence hCMEC/D3 barrier properties, whilst tPA with plasminogen did, implicating plasmins involvement. ConclusionPlasmin directly impaired the barrier function of hCMEC/D3 brain endothelial cell monolayers by stimulating a decline in key junctional molecules. This plasmin-mediated brain endothelial barrier deterioration has important implications for tPA use and should be considered whilst designing safer thrombolytic treatment options for patients experiencing acute ischemic stroke.

Background: Circulating endothelial progenitor cells (cEPCs) contribute to vascular repair following an ischemic stroke. The aim of the study was to evaluate the association between cEPCs and functional outcomes in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) who received endovascular therapy (EVT). Methods: Prospective study of patients with LVO-AIS who received EVT. Blood samples were obtained within 24 +- 12 hours and on day 7+-1 from stroke onset. cEPCs were detected using flow cytometry (CD34+/VEGFR2+/CD133+). The primary endpoint was a favourable functional outcome (modified Rankin Scale 0-2) at three months of follow-up. Secondary endpoints include baseline to 24 hours/day 7 changes in the National Institutes of Health Stroke Scale (NIHSS) score and collateral circulation (CC) status. Bivariate and multivariable logistic regression analyses were performed. Results: Included were 90 patients (73.2+-12.7 years, 41.1% women) in 42 of whom (46.7%) cEPCs were detected at 24 hours. On day 7, cEPCs were detected in 27 (43.6%) of 62 patients for which this information was available. Atrial fibrillation, prior anticoagulant treatment and stroke onset-to-door time <6 hours were associated with lower cEPC counts, and intravenous fibrinolysis therapy was associated with a higher cEPC count on day 7. No association was found between cEPCs and functional outcomes at three months. Patients with the highest cEPC count (Q4) at 24 hours had a lower probability of good CC (46.2% vs 77.3%; p=0.031). Conclusion: cEPC count in patients with LVO-AIS who received EVT was not associated with functional outcomes.

Background and Purpose: Hemorrhagic transformation (HT) is a serious complication of endovascular thrombectomy (EVT), yet dedicated prediction models for young adults are lacking. We aimed to develop and externally validate a simplified risk score for HT in young adults with acute ischemic stroke undergoing EVT. Methods: This multicenter retrospective study included patients aged 18 to 49 years with acute anterior circulation large vessel occlusion who underwent EVT. The primary outcome was any HT within 24 hours after EVT. Multivariable logistic regression was used to identify independent predictors of HT, from which the NO?PAIN Score was derived. External validation was performed in an independent cohort of 138 patients. Results: Among 598 patients in the derivation cohort, HT occurred in 176 (29.4%). Five independent predictors were identified: admission NIHSS, number of thrombectomy passes, atrial fibrillation, alcohol consumption, and mTICI grade. The mTICI grade demonstrated a non-linear, inverted U-shaped relationship with HT risk, peaking at partial recanalization. The NO-PAIN Score showed acceptable discrimination in both the derivation (C-index, 0.737; optimism-corrected C-index, 0.748) and external validation cohorts (C-index, 0.726), with satisfactory calibration. Conclusions: The NO-PAIN Score is a simple risk prediction tool for HT after EVT in young adults with acute anterior circulation large vessel occlusion. It may assist in individualized risk stratification in this population.

Stroke is a leading cause of disability and mortality worldwide, with ischaemic stroke the most prevalent type. Statins, used for cholesterol management, have demonstrated benefits in reducing stroke risk and improving outcomes in preclinical studies. However, the impact of pre-stroke statin use on stroke outcomes remain inconsistent. In this study, we aim to evaluate whether pre-stroke statin use is associated with greater volume of salvaged tissue and improved cerebral collateral perfusion. A retrospective analysis was conducted using data from 281 patients presenting with acute ischemic stroke to the John Hunter Hospital between May 2015 and May 2020. Patients were grouped based on pre-stroke statin use, and clinical variables, including infarct volume and collateral perfusion, were assessed. The primary outcome was salvage volume derived from baseline perfusion lesion volume minus infarct volume at follow-up. Collateral perfusion was measured by the hypoperfusion volume defined by delay time (DT)>6 seconds divided by the hypoperfusion volume defined by DT >2 seconds. Patients on statins at admission were significantly older and had more comorbidities. No significant association was found between pre-stroke statin use and salvage volume or collateral perfusion after adjusting for covariates. Larger initial infarct core was a significant predictor of salvage volume due to larger salvageable tissue volume at baseline. These findings indicate that pre-morbid statin use is not associated with larger salvage volume or improved cerebral collateral perfusion.

Background: Late complications after stroke (LCAS), including cognitive symptoms, impact quality of life and recovery. It is not known if neighborhood-level measures of socioeconomic status (SES) influence LCAS. This study assessed associations between SES measures, including neighborhood income inequality (Gini) and area deprivation index (ADI), and cognitive symptoms after acute ischemic stroke (AIS) in a hospital leveraging active surveillance of LCAS. Methods: This retrospective cohort study included 512 patients hospitalized with AIS at Tufts Medical Center with subsequent follow-up (between zero and three months or between three and twelve months) in the Stroke Clinic from 1/1/2018 - 12/31/2022. Using ZIP code data, patients were characterized as low Gini (low inequality) and high ADI (high deprivation) (Gini <= 0.4302, ADI >= 5) by state medians. These variables were combined, indicating patients who were living in both a low Gini and high ADI neighborhood to evaluate the effects of living in a homogeneously deprived area. There were 206 and 281 patients in the low Gini and high ADI groups respectively. 140 patients lived in a low Gini and high ADI neighborhood. The multivariable logistic analysis assessed the likelihood of cognitive symptoms, adjusting for age, race, ethnicity, sex, NIH Stroke Scale (NIHSS), thrombolysis, active LCAS surveillance, poverty, and ADI-Gini combination. Results: There were no associations between high ADI (OR: 1.03, 95% CI: 0.67 ? 1.57) or low Gini (OR: 1.74, 95% CI: 0.98 ? 3.07) alone and cognitive symptoms after AIS. However, the combined variable demonstrated increased likelihood of cognitive symptoms in the high ADI-low Gini group (OR: 1.82, 95% CI: 1.08 ? 3.06). Conclusions: This study suggests that individuals living in homogeneously deprived neighborhoods report higher likelihood of cognitive symptoms after AIS. Further studies with increased power are needed to investigate the underlying causes of these disparities and to develop interventions to reduce these complications.

Background. Up to 70% of stroke survivors develop cognitive impairment, yet clinicians lack non-invasive vascular biomarkers that could meaningfully inform risk stratification. Carotid-femoral pulse wave velocity (cfPWV), the gold-standard measurement of central arterial stiffness, is a novel biomarker of vascular aging linked to cognitive impairment. This study evaluated the association between cfPWV and post-stroke cognitive impairment, as measured by the Montreal Cognitive Assessment (MoCA), in individuals [&ge;]6 months post-stroke. Methods. This is a secondary cross-sectional analysis of baseline data from a randomized control trial. Logistic regression analyses examined the association between cfPWV (m/s) and MoCA score at the primary cut point of [&le;]26/30, with secondary cut points of [&le;]24/30 and [&le;]22/30. Models were adjusted for age, sex, systolic blood pressure, type-2 diabetes, National Institutes of Health Stroke Scale (NIHSS) score, and smoking status. Results. Of 82 participants enrolled in the main trial, 68 participants (n = 45 males, age 64.6 {+/-} 9.6 years, 1.8 {+/-} 1.2 years post-stroke) with mild-to-moderate stroke severity (NIHSS median [IQR] = 1 [2]) were included. In the fully adjusted model using the MoCA [&le;]26/30 cut point, each 1 m/s increase in cfPWV was associated with a 35% increase in the odds of post-stroke cognitive impairment (adjusted OR [aOR] = 1.35; 95% CI 1.06, 1.81; p = 0.027; Area Under the Curve [AUC] = 0.77). Consistent associations were observed at the MoCA [&le;]24/30 (aOR = 1.41; 95% CI 1.04, 2.01; p = 0.037; AUC = 0.88) and MoCA [&le;]22/30 (aOR = 1.33; 95% CI 1.03, 1.79; p = 0.039; AUC = 0.82) cut points. Conclusions. Higher cfPWV was independently associated with post-stroke cognitive impairment across clinically referenced MoCA cut points. cfPWV may be a complementary vascular biomarker to support cognitive risk stratification and identify stroke survivors who could benefit from closer monitoring or vascular-targeted intervention.

Background:Stroke continues to be one of the major causes of death and long-term disability worldwide, with a greater impact in low-and middle-income countries. In India, there is limited evidence examining stroke burden and its changes over time and across regions. Therefore, we aimed to assess the burden of stroke in India from 1990 to 2023 using the latest data from the Global Burden of Disease (GBD) Study, along with projections up to 2035. Methods:We used estimates from the GBD 2023 study to examine stroke incidence, prevalence, mortality, and disability-adjusted life years (DALYs) in India from 1990 to 2023. Age-standardized rates were analyzed to understand how these measures have changed over time. We also conducted state-level analyses to explore regional differences in stroke burden. The contributions of all major modifiable risk factors were assessed using population-attributable fractions. In addition, we projected future trends in stroke burden up to 2035. Results:From 1990-2023, the percentage change in overall stroke burden in India showed minimal variation across key indicators. Incidence remained largely stable (0.00%[-0.04 to 0.05]), while prevalence showed a slight increase(0.06%[0.03 to 0.10]). Mortality (-0.11%[-0.36 to 0.20]) and DALYs (-0.17%[-0.38 to 0.12]) demonstrated modest declines over the study period. Notable regional disparities were evident, with states such as Chhattisgarh, Assam, and Jharkhand bearing the highest burden. High systolic blood pressure remained the leading risk factor in 2023, contributing the largest share of stroke-related deaths, followed by dietary risks, air pollution, tobacco use, and high body mass index. Future projections indicate that by 2035, stroke prevalence is likely to increase, while incidence, mortality, and DALYs are expected to show only modest changes. Conclusions: Stroke remains a major and growing public health challenge in India with a continuing increase in burden despite slight improvements in age-standardized rates over time. Addressing this challenge will require stronger prevention efforts, better control of key risk factors, and focused strategies to reduce regional disparities in stroke burden nationwide.

Background: Patients in socioeconomically disadvantaged neighborhoods face barriers to care. Missing BP documentation may signal gaps in risk-factor management, a crucial component of primary and secondary prevention of intracerebral hemorrhage (ICH). We tested whether neighborhood deprivation was associated with absent electronic health record (EHR) blood pressure (BP) documentation surrounding ICH and whether absent documentation predicted subsequent uncontrolled BP. Methods: We conducted a case-only study within the NIH All of Us Research Program. We included ICH survivors (ICD-10 I61.x, surviving >=1 year) with available ZIP3-based Deprivation Index. Deprivation was categorized as Privileged, Intermediate, or Deprived using cohort-based tertiles. We excluded BP measurements collected by All of Us. Outcomes were (1) absent EHR-derived BP documentation and (2) uncontrolled BP (mean systolic BP >=140 mmHg) during three windows: 1-365 days before ICH; 30-365 days and 1-5 years after ICH. Multivariable logistic regression tested associations adjusting for age, sex, and race/ethnicity. Results: 1,474 ICH survivors were included (mean age 60.1, 50.4% female). Compared to privileged neighborhoods, those living in deprived neighborhoods had higher odds of absent EHR BP documentation in the year prior to ICH (OR 2.10, 95% CI 1.60-2.76; p<0.001), 30-365 days post-ICH (OR 2.82, 95% CI 2.14-3.73; p<0.001) and 1-5 years post-ICH (OR 2.81, 95% CI 2.13-3.71; p<0.001). Absence of EHR BP documentation in the year before ICH predicted uncontrolled BP 30-365 days (OR 1.97, 95% CI 1.36-2.85; p<0.001; N=888) and 1-5 years (OR 1.83, 95% CI 1.24-2.69; p=0.002; N=814) after ICH. Absence of BP documentation 30-365 days post-ICH also predicted uncontrolled BP 1-5 years post-ICH (OR 1.66, 95% CI 1.10-2.50; p=0.017; N=814). Conclusions: Neighborhood deprivation is associated with persistent gaps in EHR BP documentation surrounding ICH, and absent documentation before or soon after ICH predicts subsequent uncontrolled BP. These findings highlight the need for community-level strategies that ensure equitable BP monitoring for socioeconomically disadvantaged populations.

Background and Purpose: Futile interhospital transfers, where patients transferred for endovascular thrombectomy (EVT) do not ultimately receive the procedure, represent a critical systemic burden on stroke transfer network. Whether pre-transfer computed tomography angiography (CTA) at the primary stroke center (PSC) reduces futile transfers, and at what workflow cost, remains incompletely characterized. Methods: This retrospective study enrolled 314 acute ischemic stroke patients transferred for potential EVT within the Tainan-Chiayi Stroke Network (October 2021-September 2025). Patients were stratified by CTA timing: pre-transfer (n=66) versus post-transfer (n=248). Workflow time metrics and 90-day functional outcomes were compared. Futile transfers were classified into three categories: preventable over-triage, physiological futility, and gray zone cases. Results: The futile transfer rate was substantially lower in the pre-transfer CTA group (27.3% vs. 66.1%; P<0.001), with post-transfer CTA as the strongest independent predictor of futility (aOR 5.21; 95% CI 2.83-9.60). In the post-transfer CTA group, 40.2% of futile transfers involved conditions identifiable by pre-transfer CTA. Regardless of CTA timing, gray zone cases predominated in both groups (83.3% vs. 47.6%), driven by intracranial atherosclerotic stenosis/ chronic total occlusion, large infarct cores, and medium vessel occlusions. Pre-transfer CTA significantly prolonged PSC door-in-door-out time (140 vs. 88 min; P<0.001) and showed numerical trends toward longer onset-to-EVT time and lower rates of favorable functional outcome. Conclusions: Adopting CTA during the pre-transfer period reduces preventable futile transfers but prolongs PSC processing time. Nevertheless, the persistent gray zone requires strategies beyond imaging alone, and the trade-off between triage precision and transfer efficiency warrants ongoing evaluation across different stroke networks settings.-

Introduction Stroke is a leading cause of disability and death in adults with type 2 diabetes (T2D). We evaluated the comparative stroke risk in Veterans with T2D initiated on either of two glucose-lowering medications: GLP-1 receptor agonists (GLP-1RA) or SGLT-2 inhibitors (SGLT2i). Patients and Methods We conducted a retrospective cohort study on diabetic Veterans aged 40 and older with no prior history of stroke or transient ischemic attack, who started on a GLP-1RA or SGLT2i between 2014 and 2021. Patients with contraindications or prior exposure to medication were excluded. Using national Veteran health data, we identified 195,072 [SS1.1]eligible individuals and followed them from treatment initiation until stroke, death, loss to follow up, or end of follow up, whichever came first. Primary outcome was incident stroke, and secondary outcomes included ischemic and hemorrhagic stroke. We applied Kaplan-Meier methods and Cox proportional hazards models. Adjusted associations were estimated using inverse probability weighting. Results Both unadjusted and adjusted analyses suggest GLP-1RA users have reduced stroke incidence compared SGLT-2i users[HS2.1] (HR = 0.[HS3.1]67, 95% CI 0.64-0.69; HR = 0.72, 95% CI 0.69-0.75). Similar results were found in secondary outcome and stratified analyses, with GLP-1RA users having reduced stroke risk compared to SGLT2i users for all age groups, chronic kidney disease stages, and hemoglobin A1c levels. Discussion and Conclusion GLP-1RA treatment was associated with a lower risk of stroke compared with SGLT2i treatment in Veterans with T2D. These findings were consistent for ischemic and hemorrhagic strokes, suggesting potential differences in stroke risk between the treatments.

INTRODUCTION Severe acute brain injury (stroke, traumatic brain injury or hypoxic-ischemic encephalopathy; SABI) is increasingly recognized as a chronic condition with care and communication needs beyond the initial hospitalization. This study aimed to characterize post-acute care patterns among SABI survivors, focusing on healthcare utilization and outpatient communication. METHODS Data were collected from a prospective cohort of hospitalized SABI patients using surveys, chart reviews, and the ED Information Exchange database. Socioeconomic disadvantage was assessed using the Area Deprivation Index (ADI), and qualitative analysis of outpatient notes examined conversations around palliative care needs and goals-of-care. RESULTS Two-thirds of patients (140/222) survived until discharge, primarily to nursing facilities (39%) or inpatient rehabilitation (38%). Among 109 with one-year follow-up, there were 89 hospitalizations, 104 ED visits, and 28 deaths. Patients from the most disadvantaged neighborhoods had significantly higher odds of rehospitalization or ED use within 30 days (OR 3.37, p=0.036). ADI was not linked to one-year utilization. seen outpatient by primary care (40%), neurology/neurosurgery (57%), and palliative care (1%), but conversations rarely revisited prognosis or goals-of-care. CONCLUSIONS Our findings highlight the need for improved long-term care planning and communication, particularly for socioeconomically disadvantaged survivors of SABI.

Background: The Functional Outcome in Patients with Primary Intracerebral Hemorrhage (FUNC) score was initially validated for prediction of functional independence on the Glasgow Outcome Scale (GOS) 90 days after intracerebral hemorrhage (ICH), but recovery often extends beyond three months. Aims: Our objective was to extend the FUNC score for prediction of 12-month functional independence to strengthen its utility for family counseling and research methodology. Methods: We conducted a single-center prospective cohort study enrolling adult patients with primary ICH between February 2009 and January 2018. We calculated FUNC scores at admission and assessed GOS 12 months after ICH. The primary outcome was 12-month functional independence, defined as a GOS score [&ge;]4. We calculated the area under the receiver operating characteristic curve (AUC) of the FUNC score using logistic regression, handling missing GOS with multiple imputation by chained equations. We evaluated score calibration using a calibration curve and the Brier score, and we assessed clinical utility using decision curve analysis. We explored the statistical efficiency gains of using FUNC-based sliding dichotomy thresholds for favorable outcome definitions by running simulations of a clinical trial with 1:1 randomization. We ran 5000 simulations for each sample size (100 to 1000, in increments of 10) and treatment effect (odds ratio of 1.5, 2.0 and 2.5) combination and calculated efficiency gains for each respective treatment effect as the percentage reduction in sample size required to have 80% power using sliding versus fixed dichotomy thresholds. Results: A total of 535 patients were included (median [IQR] age 68 [54-79], 237 [44%] female, median [IQR] NIHSS 16 [6-25], median [IQR] FUNC 8 [6-9]). Overall, 99 of 445 (22%) patients with known 12-month GOS achieved functional independence. The FUNC score had an AUC of 0.79 (95%-CI: 0.75-0.84) for 12-month functional independence. The calibration plot was reasonable, with modest evidence of overestimation at low predicted probabilities, and the Brier score was 0.15. A net benefit was observed across 5-50% threshold probabilities. Sliding dichotomy had an efficiency gain of 27% for a treatment effect of OR=2.0, and a gain of 22% for a treatment effect of OR=2.5. The efficiency gain for a treatment effect of OR=1.5 could not be calculated because the fixed dichotomy did not reach 80% power despite a sample size of 1000 patients. Conclusions: The FUNC score's predictive performance for 12-month functional independence was comparable to its originally validated 3-month discrimination. Following external validation across centers, the FUNC score may be leveraged to counsel families on global measures of long-term functional independence and to implement sliding dichotomy methodology in ICH research.

Background and Purpose Prognostication after acute ischemic stroke often relies on limited variables and simple risk scores, despite richer information being available at admission. We developed a multimodal AI model using admission data to predict modified Rankin Scale (mRS) outcomes and compared it to established tools. Methods In a retrospective study of ischemic stroke/TIA patients, we trained three modality-specific models on admission non-contrast head CT, history and physical notes, and structured clinical variables, and combined them in a weighted-average ensemble. We predicted binary (mRS 0-2 versus 3-6) and ordinal mRS (0-6) outcomes at discharge and 90 days. Performance on an external test cohort was compared with THRIVE and SPAN-100 scores using AUROC, AUPRC, Brier score, mean absolute error (MAE), and quadratic weighted kappa (QWK). Results A total of 6,915 patients were split into training, validation and testing cohorts in a 3:1:1 ratio. For discharge binary mRS (n=1596), the multimodal ensemble achieved significantly better discrimination (AUROC 0.859, AUPRC 0.858) with 25-61% lower Brier scores than THRIVE or SPAN?100 (all p<0.001). For 90?day binary mRS (n=207), the model also outperformed both THRIVE and SPAN-100 (AUROC 0.838, AUPRC 0.805, with 3-38% lower Brier scores). Ordinal mRS prediction showed similarly strong performance with significantly better QWK at discharge and numerically lower MAE. The multimodal ensemble model reassigned about one?third of patients to different risk categories versus THRIVE and was closer to the true discharge outcome in ~74% of discordant cases. Conclusions We developed a well-calibrated multimodal AI model for prediction of discharge and 90-day post-stroke functional outcomes using only data present at the time of admission. This model outperforms existing prognostic tools and can support early clinical decision-making.

Background: Post-operative hypotension and vasoplegia are well recognised following cardiac surgery but remain poorly characterised after major non-cardiac surgery, despite associations with acute kidney injury (AKI), cardiovascular complications, and increased mortality. Dysregulation of the renin angiotensin aldosterone system (RAAS) may underpin haemodynamic instability in this setting, yet data in abdominal surgery are limited. Objectives: The POLECAT (Perioperative delta Renin) study aims to determine whether changes in circulating renin concentration (delta renin) from pre-operative baseline to the early post-operative period are associated with post-operative vasoplegia in patients undergoing major abdominal surgery requiring intensive care admission. Methods: POLECAT is a single-centre, prospective observational study conducted at a UK tertiary referral hospital. Adult patients undergoing planned or emergency abdominopelvic surgery with anticipated intensive care admission are enrolled. Blood samples are obtained pre-operatively, within four hours post-operatively, and on post-operative day one to measure renin and a panel of endothelial, renal, and immune biomarkers. The primary outcome is post-operative vasoplegia, defined as the requirement for a vasopressor infusion at 08:00 on post-operative day one. Secondary outcomes include alternative vasoplegia definitions, AKI (KDIGO criteria), vasopressor burden, organ dysfunction, cardiovascular complications, length of stay, and mortality. Multivariable regression, receiver operating characteristic analyses, and predefined subgroup analyses will be performed, with sensitivity analyses addressing missing data. Conclusions: This study will clarify the relationship between peri-operative RAAS dysfunction and vasoplegia following major abdominal surgery. Findings may support biomarker-guided risk stratification and inform future interventional trials targeting haemodynamic instability in this high-risk population.

Background: Immune-mediated mechanisms are increasingly implicated in childhood arterial ischemic stroke (AIS), but the associated inflammatory pathways and how they differ by stroke subtype and outcome remain poorly understood. Understanding immune responses to AIS may identify subtype-specific mechanisms and inform targeted strategies to reduce ischemic injury. Methods: We conducted a prospective cohort study with cross-sectional transcriptomic analysis through the Vascular Effects of Infection in Pediatric Stroke Study Part II (VIPS II) at 22 academic centers in the United States, Canada, and Australia between December 2016 and January 2022. Children aged 28 days to 18 years with centrally confirmed AIS were enrolled within 72 hours of stroke onset, in addition to enrollment of stroke-free well children. Peripheral blood RNA sequencing was performed on samples collected within 72 hours of stroke or at enrollment for controls. Differential gene expression (DGE) and pathway analyses were performed comparing all AIS cases to stroke-free well children. Additional cross-sectional analyses stratified by stroke subtype and neurological outcomes were performed. Results: Transcriptomes were available in 190/205 AIS cases (median age 11.7 years) and 91/100 stroke-free children (11.8 years). Stroke subtypes included 67 definite arteriopathic, 74 probable arteriopathic, 23 cardioembolic, and 26 idiopathic, with similar demographics but smaller infarct size for idiopathic cases. 47 genes (false discovery rate (FDR) <0.05 and log2 fold-change (log2FC)>1) were differentially expressed in AIS versus stroke-free well children, with upregulated pathways reflecting innate immune responses. Stratification by subtype revealed these inflammatory responses occurred after arteriopathic and cardioembolic AIS, but not idiopathic AIS; in sensitivity analyses, these findings were not explained by infarct size. Four immune-related genes were differentially expressed in children with good versus poor neurological outcomes at hospital discharge or 12 months; upregulation of one (Joining Chain; JCHAIN) correlated with poor outcomes at both timepoints. Conclusions: Compared with stroke-free children, children with AIS, particularly arteriopathic and cardioembolic subtypes, have upregulated innate immune pathways, including neutrophil activation and interleukin-1 signaling. Differential expression of immune-related genes also correlated with neurological outcomes. These findings support immune dysregulation as a key feature of early pediatric AIS while highlighting differences across subtypes and clinical outcomes, with implications for targeted immunomodulatory therapies and future biomarker development.

Objective: Outcome after surgical hematoma evacuation for intracerebral hemorrhage (ICH) depends on hematoma location. As corticospinal tract (CST) integrity affects motor recovery after stroke, we hypothesized that CST integrity drives heterogeneity in surgical outcomes and investigated this in a secondary analysis of MISTIE-III participants. Methods: Risk of CST injury was categorized into four levels, based on the interaction between the CST, the hematoma, and perihematomal edema (PHE) on automatically segmented stability CT: no risk, PHE infiltration, hematoma infiltration, and complete interruption of the CST. Associations with outcome were tested using multivariable linear regression for motor National Institutes of Health Stroke Scale (NIHSS) at day 180 and ordinal regression for modified Rankin Scale (mRS) at day 365, introducing an interaction term between CST risk and treatment group. Results: Day 180 motor NIHSS was significantly lower for 'no risk' ({beta}:-3.77, [95% confidence interval [CI]: -5.8 to -1.70], p=0.0003) and 'PHE infiltration' ({beta}:-2.3, [95%CI: -3.5 to -1.1]; p=0.0002) vs. 'complete interruption'. Surgery was associated with lower Day 180 motor NIHSS in participants with hematoma infiltration ({beta}:-2.07, [95%CI: -3.8 to -0.4], p=0.016). Compared to complete interruption, 'no risk' (adjusted odds ratio [aOR]:0.27, [95%CI: 0.10 to 0.74], p=0.01) and 'PHE infiltration' (aOR:0.41, [95%CI: 0.23 to 0.74]; p=0.003) were associated with lower odds of unfavorable day 365 mRS. Surgery was associated with lower mRS in participants with no risk (aOR:0.23, [95%CI: 0.05 to 0.97, p=0.045). Interpretation: Increasing CST risk is associated with worse motor recovery (day 180) and disability (day 365). CST risk modifies the effect of the MISTIE-III procedure on motor recovery and disability.

Purpose: Polypharmacy is highly prevalent among critically ill patients, yet it's independent impact on intensive care unit (ICU) outcomes in sepsis remains critically unexplored. We aimed to evaluate whether pre-admission polypharmacy independently predicts ICU mortality and provides incremental prognostic value using the medication reconciliation module of the MIMIC-IV-ED linked database. Materials and Methods: We conducted a retrospective cohort study of 3,347 adults admitted to the ICU who met Sepsis-3 criteria. Pre-admission polypharmacy was categorized as none (0-4), standard (5-9), or high (>=10 medications). Multivariable logistic regression, propensity score matching, and reclassification analyses (NRI/IDI) were performed. The primary outcome was in-hospital ICU mortality. Results: High polypharmacy was present in 58.9% of patients. Crude ICU mortality increased sequentially: 18.5% (none), 26.0% (standard), and 27.5% (high; p < 0.001). After multivariable adjustment, high polypharmacy independently predicted in-hospital ICU mortality (aOR 1.45, 95% CI (1.10-1.91)), and 28-day mortality (aOR 1.47). Drug-class analysis identified statins as significantly protective (aOR 0.56), whereas RAS blockers combined with diuretics increased acute kidney injury risk (aOR 1.49). Propensity matching confirmed the primary mortality association (matched aOR 1.28). Conclusions: By utilizing the ED medication reconciliation table, this study proves high polypharmacy represents a distinct 'pharmacologic frailty', independent of acute severity. Available instantly at triage, this zero-latency metric provides significant early prognostic value (SOFA NRI = 0.24) and identifies actionable high-risk interactions (e.g., RAS blockers plus diuretics) for immediate, targeted pharmacist-led intervention upon ICU admission.

IntroductionCoronary artery disease (CAD) increases the risk of cerebrovascular events, yet early brain injury in this population remains poorly characterized. White matter hyperintensities (WMHs), a biomarker of cerebrovascular lesions, are prevalent in CAD and are linked to risk of stroke. Beyond total burden, spatial distribution of WMHs carries pathological significance and is critical for understanding CAD-related injury. While clinical outcomes including coronary revascularization procedure and myocardial infarction influence CAD prognosis, their impact on WMH burden remains unclear. MethodsThis study investigated regional WMH burden in CAD and its relationship with clinical characteristics. 82 adults over 50 years participated, including 44 individuals with CAD and 38 controls. WMHs were segmented from fluid attenuated inversion recovery and T1-weighted MRI and categorized as total, periventricular, deep, and superficial regions. History of myocardial infarction and coronary revascularization (coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI)), was obtained from medical files. ResultsIndividuals with CAD exhibited higher total, periventricular, and deep WMH volumes than controls. Participants who underwent CABG had higher superficial WMH volumes than those with PCI, suggesting greater disease severity influences WMH burden. ConclusionCAD is characterized by a distinct pattern of cerebrovascular vulnerability, with revascularization procedures influencing WMH burden

Background: Depression and heart disease frequently co-occur in the aging population and are associated with functional decline and poor health outcomes. Understanding how depressive symptoms relate to different aspects of physical function among adults with heart disease may help identify high-risk subgroups. Objective: To examine the association of depressive symptoms with self-reported and observed physical function measures among participants with heart disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and assess whether associations differ by sex and race?sex groups. Methods: We conducted a cross-sectional analysis using data from REGARDS study second in-home visit (2013?2016). Depressive symptoms were measured with the 10-item Center for Epidemiologic Studies Depression scale (CES D 10), considering scores ?10 as clinically significant. Physical function measures were instrumental activities of daily living (IADL), activities of daily living (ADL), chair stand time (5 repetitions), and gait speed. Linear regression models estimated associations of depressive symptoms with function, adjusting for sociodemographic, health behavior, antidepressant medications, body mass index, and social support. Effect modification by sex and race?sex group was evaluated. Results: Among 3,055 participants, 11.7% had CES D 10 ?10. Compared to CES-D-10 scores <10, CES D 10 ?10 was associated with more limitations in IADL (1.84 points; 95% CI 1.62, 2.06), ADL (0.43 points; 95% CI 0.34, 0.52) and slower chair stand time (0.88 second; 95% CI 0.07, 1.69); associations with gait speed were modest (?0.04 meters/second; 95% CI ?0.08, -0.01). Women had a stronger association between CES-D-10 and ADL (0.49 points; 95% CI 0.35, 0.64) than men (0.33 points; 95% CI 0.21, 0.44; p for interaction = 0.01). Interaction between CES D 10 and race?sex groups was not statistically significant. Conclusions: Among adults with heart disease, clinically significant depressive symptoms were associated with lower physical function, particularly among women.

Introduction Cardiovascular disease (CVD) remains Vietnam's leading cause of mortality, yet no comprehensive national analysis of burden trends and future projections exists. This study characterizes Vietnam's CVD burden from 1990 to 2023 and projects burden through 2050. Methods Using Global Burden of Disease 2023 data, we analyzed CVD prevalence, incidence, mortality, and disability-adjusted life years (DALYs) in Vietnam from 1990 to 2023, stratified by sex and age. Joinpoint regression quantified temporal trends. Decomposition analysis separated contributions of population growth, aging, and epidemiological change. ARIMA modeling, validated against pre-pandemic and COVID 19 periods, projected burden through 2050. Results Despite age-standardized CVD prevalence below global estimates, stroke mortality and DALYs rates exceeded global benchmarks. Age-standardized CVD mortality (ASMR) declined significantly (average annual percentage change [APC]:-1.34%), yet absolute deaths nearly doubled from 121,611 to 223,068. Population aging contributed 140.9% to observed mortality increases while epidemiological improvements averted over 102,000 deaths. Male age-standardized CVD mortality was approximately twice that of females. High systolic blood pressure remained the leading attributable risk factor, while high BMI and alcohol use showed the largest rank escalations. CVD incidence reversed its declining trend during 2019 - 2023 (APC:+0.69%). By 2050, ASMR are projected to decline by 51.0% (218.8 to 107.1 per 100,000 [95%CI: 64.1 - 150.2]), while absolute deaths are projected to increase by 43.4% (206,677 to 296,335 [95%CI: 272,323 - 320,348]). Conclusions Vietnam faces a demographic paradox of improving age-specific outcomes alongside a rising absolute burden driven by population aging, demanding urgent reorientation toward aging-specific prevention, hypertension control, and chronic cardiovascular care.