• Combined assessment of ASPECTS and collateral status predict outcomes after endovascular therapy in patients with large ischemic stroke.
    3 days ago
    Both the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and collateral status are well-established predictors of clinical outcomes in patients with large ischemic stroke undergoing endovascular therapy (EVT); however, they have traditionally been assessed independently. This study aimed to evaluate the prognostic value of a combined imaging score, the AS-TCIS score, which integrates ASPECTS and collateral status into a unified framework.

    This study is a subanalysis of a prospective multicenter cohort including patients with ASPECTS ≤5 enrolled between November 2021 and February 2023. The AS-TCIS score was constructed by integrating the 5-point ASPECTS with collateral status, including the 3-point Tan score and the 8-point comprehensive venous outflow (CVO) score, yielding a 16-point composite scale. The primary outcomes were 90-day functional outcome (modified Rankin Scale [mRS] 0-3) and mortality.

    Of 750 patients, 287 were eligible (median age 67 years; 58.5% male; median AS-TCIS score 8). In multivariable models, each 1-point increase in AS-TCIS was associated with higher odds of mRS 0-3 (OR 1.38; 95% CI 1.24-1.56) and mRS 0-2 (OR 1.30; 95% CI 1.17-1.47), and lower odds of mortality (OR 0.74; 95% CI 0.66-0.82), with no significant association with symptomatic intracranial hemorrhage (OR 0.92; 95% CI 0.82-1.03). AS-TCIS also demonstrated a linear association with functional outcome and mortality. Compared with ASPECTS, Tan score, and their combination, AS-TCIS showed consistently higher AUCs and improved model fit across all outcomes.

    The AS-TCIS score, a composite of ASPECTS and collateral status, was independently associated with 90-day outcomes in patients with large ischemic stroke undergoing EVT. It may provide incremental value for risk stratification and outcome prediction in acute stroke imaging assessment.
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  • Microembolic signals in transcranial Doppler and the functional outcome of patients with acute ischemic stroke: a meta-analysis.
    3 days ago
    Microembolic signals (MES) detected by transcranial Doppler ultrasonography (TCD) reflect ongoing cerebral embolization and may serve as a marker of stroke instability. However, the association between MES and functional outcomes in patients with acute ischemic stroke (AIS) remains uncertain. This meta-analysis aimed to evaluate the prognostic significance of MES for poor functional outcomes after AIS.

    PubMed, Embase, Web of Science, Wanfang Data, and CNKI databases were searched for cohort studies comparing functional outcomes between AIS patients with and without MES. The primary outcome was poor functional outcome, defined as a modified Rankin Scale score of 3-6 during follow-up. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using a random-effects model accounting for the influence of potential heterogeneity.

    Thirteen cohort studies involving 1,777 patients with AIS were included, of whom 361 (20.3%) had detectable MES. Overall, MES was associated with a significantly increased risk of poor functional outcome (OR: 2.85, 95% CI: 2.16-3.75; p < 0.001) with no significant heterogeneity (I 2 = 0%). Subgroup analyses demonstrated consistent results across prospective and retrospective studies, and the observed association was not significantly influenced by patient age, sex distribution, endovascular treatment status, TCD monitoring duration, analytical model, or study quality (all p for subgroup difference > 0.05). MES was associated with poor functional outcomes at discharge (OR: 3.60), 14 days (OR: 2.69), and 90 days (OR: 3.15).

    MES detected by TCD are associated with an increased risk of poor functional outcome in patients with AIS. However, their independent and incremental prognostic value beyond established clinical and imaging predictors requires further confirmation.

    The review protocol was prospectively registered in PROSPERO (CRD420261425262).
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  • Blood pressure variability and parenchymal hematoma after endovascular thrombectomy: effect modification by recanalization status and cerebral small vessel disease burden.
    3 days ago
    We investigated the association between post-thrombectomy blood pressure variability (BPV) and parenchymal hematoma (PH), and whether this relationship is modified by persistent vessel patency and cerebral small vessel disease (CSVD) burden.

    We analyzed 302 patients with acute ischemic stroke who underwent endovascular thrombectomy. PH was defined as confluent hemorrhage with a mass effect. BPV was assessed using 2-h blood pressure measurements during the first 24 h. Parameters included the maximum, minimum, mean, range, standard deviation, coefficient of variation, and successive variation of systolic, diastolic, and pulse pressure (PP). CSVD burden was quantified using the total CSVD score and dichotomized into none-to-mild (score 0-1) and moderate-to-severe (score 2-4). Multivariable logistic regression models were used to evaluate associations and interaction effects.

    PH occurred in 78 patients (25.8%). Among BPV parameters, pulse pressure successive variation (PPSV) showed favorable model performance and was selected for interaction analyses. Significant interactions were observed between PPSV and persistent vessel patency (Pinteraction  = 0.003) and between PPSV and CSVD burden (Pinteraction  = 0.007). In stratified analyses, higher PPSV was associated with PH in patients with sustained major vessel patency (OR, 2.67 [95% CI, 1.79-3.97]; p < 0.001) and in those with none-to-mild CSVD (OR, 2.61 [95% CI, 1.74-3.94]; p < 0.001) but not in those with persistent occlusion or moderate-to-severe CSVD.

    Increased post-thrombectomy BPV, particularly PP variability, was independently associated with PH, with effects modified by persistent vessel patency and CSVD burden. These findings suggest individualized blood pressure management based on macrovascular persistent vessel patency and underlying microvascular integrity.
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  • Sociodemographic factors associated with depressive symptoms and self-care agency capacity in hypertensive older adults from Loja, Ecuador: a cross-sectional study.
    3 days ago
    Hypertension is one of the leading chronic diseases affecting older adults and is frequently associated with depressive symptoms and difficulties in self-care. Sociodemographic conditions may influence both mental health and self-care behaviors; however, evidence in older hypertensive populations from Ecuador remains limited. Therefore, this study aimed to analyze the association between sociodemographic factors, depressive symptoms, and self-care agency capacity among older adults with hypertension living in Loja, Ecuador.

    A cross-sectional study was conducted among 222 older adults diagnosed with hypertension residing in urban, rural, and urban-marginal areas of Loja, Ecuador. Depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II), while self-care agency capacity was evaluated using the Self-Care Agency Capacity Scale for Patients with Hypertension. Descriptive analyses, Spearman correlation, bivariate analyses, and multiple linear regression models were performed, adjusted for sociodemographic variables.

    Most participants showed high self-care agency capacity (69.4%), whereas 84.2% presented minimal depressive symptoms. After adjustment, place of residence remained independently associated with self-care agency capacity, with participants living in urban-marginal areas showing higher self-care agency capacity scores than those residing in rural areas. Depressive symptoms were significantly associated with sex, age and place of residence. No statistically significant correlation was observed between depressive symptoms and self-care agency capacity (rho = 0.111; p = 0.100).

    Sociodemographic factors were associated with both depressive symptoms and self-care agency capacity among older adults with hypertension. These findings highlight the importance of considering social determinants and mental health conditions in the comprehensive management of chronic diseases in older populations.
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  • Micro-bursts matter: vigorous intermittent lifestyle physical activity and risk of common brain disorders in a prospective cohort study.
    3 days ago
    Physical activity, particularly moderate-to-vigorous physical activity, is important for brain health; however, many adults do not meet recommended activity levels. Vigorous intermittent lifestyle physical activity (VILPA) may provide a feasible alternative. This study examined the associations of accelerometer-derived vigorous intermittent lifestyle physical activity with the risk of five common brain disorders.

    This prospective cohort study used accelerometer data from the UK Biobank to quantify daily VILPA according to both duration and standardized frequency, using bouts lasting up to 1 min and up to 2 min. Incident anxiety, depression, dementia, Parkinson's disease, and stroke were ascertained through linked health records. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline models were applied to examine dose-response associations. Analyses were further stratified by exercise habit status.

    During a median follow-up of approximately 8 years, 2,150 anxiety (2.47%), 1,511 depression (1.81%), 676 dementia (0.74%), 343 Parkinson's disease (0.37%), and 1,385 stroke cases (1.55%) were identified. Higher VILPA frequency and duration were associated with lower risks of several brain disorders. Compared with the lowest quartile, modest VILPA levels were associated with reduced risks of anxiety (HR = 0.80, 95% CI: 0.71-0.90), depression (HR = 0.86, 95% CI: 0.75-0.99), dementia (HR = 0.72, 95% CI: 0.59-0.88), and Parkinson's disease (HR = 0.58, 95% CI: 0.43-0.78). Associations with stroke were weaker and less consistent. Dose-response analyses showed inverse nonlinear associations for anxiety, depression, dementia, and Parkinson's disease, characterized by a steep initial decline followed by a gradual plateau. Similar patterns were observed among both exercisers and non-exercisers.

    VILPA was associated with lower risks of several common brain disorders. Incorporating brief bursts of vigorous movement into daily life may represent a feasible strategy for promoting brain health.
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  • A cardiometabolic risk phenotype index integrating insulin resistance, systemic inflammation, and psychological burden for mortality risk stratification in metabolic dysfunction-associated steatotic liver disease: an exploratory longitudinal analysis of a nationally representative cohort.
    3 days ago
    Metabolic dysfunction-associated steatotic liver disease (MASLD) is being increasingly recognized as a systemic cardiometabolic disorder rather than a liver-limited condition. However, the combined association of insulin resistance, systemic inflammation, and depressive symptoms with mortality remains unclear. Therefore, we developed an insulin resistance-systemic inflammation-psychological burden (ISP) index to evaluate its associations with all-cause mortality (ACM) and cardiovascular mortality (CVM).

    We analyzed data from 3,187 adults with MASLD in the 2005-2018 National Health and Nutrition Examination Survey. A random forest model based on mean decrease in accuracy was used to select representative markers from six insulin resistance surrogates and five systemic inflammation indices, which were combined with the PHQ-9 score to construct the ISP index. Weighted Kaplan-Meier and Cox analyses, restricted cubic splines, subgroup and sensitivity analyses, and interpretable machine learning with 5-fold cross-validation were performed.

    During a median 8.25-year follow-up, 382 deaths occurred, including 114 cardiovascular deaths. The metabolic score for insulin resistance (METS-IR) and systemic inflammation response index (SIRI) were selected and combined with the PHQ-9 score to construct the ISP index. In fully adjusted Cox models, the highest ISP tertile was associated with higher risks of both ACM (HR = 1.63, 95% CI: 1.12-2.38) and CVM (HR = 2.88, 95% CI: 1.36‒6.10) compared with the lowest tertile. Eight ISP-based machine-learning models were internally evaluated using 5-fold cross-validation, with the GBM model yielding 10-year AUCs of 0.869 for ACM and 0.883 for CVM. SHAP analysis of the GBM model revealed that the ISP index ranked second in feature importance after age.

    The ISP index was positively associated with the risks of ACM and CVM among individuals with MASLD. However, because the ISP index was constructed and internally evaluated within the same sample, its apparent predictive performance may be optimistic owing to overfitting. Therefore, the ISP index requires external validation in larger, independent prospective cohorts.
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  • Piezo1-Src signaling rapidly disrupts brain endothelial barrier integrity.
    3 days ago
    Blood-brain barrier integrity is essential for central nervous system homeostasis, yet the mechanisms underlying ultra-acute barrier dysfunction after abrupt hemodynamic changes remain incompletely understood. Piezo1 is a mechanosensitive Ca²⁺ channel expressed in endothelial cells and activated by mechanical stimuli such as shear stress, but its contribution to rapid brain endothelial barrier disruption remains unclear. We investigated whether Piezo1 activation induces an ultra-acute disruption of the endothelial barrier and explored the underlying signaling mechanisms.

    Human brain microvascular endothelial cells (HBEC-5i) were stimulated with the Piezo1 agonist Yoda1 in the presence or absence of the Src inhibitor saracatinib, followed by barrier-function assessment and phosphoproteomic profiling. To assess in vivo relevance, vascular permeability was evaluated within minutes after reperfusion in a mouse cerebral ischemia-reperfusion model treated with the mechanosensitive channel inhibitor GsMTx4.

    Comprehensive phosphoproteomic profiling after Piezo1 activation revealed enrichment of phosphorylation events associated with cell junctions, adhesion, and cytoskeletal organization. Yoda1 induced rapid phosphorylation of junction-associated proteins, including occludin at Tyr287, and caused acute barrier disruption in HBEC-5i cells. Saracatinib attenuated occludin Tyr287 phosphorylation and preserved barrier integrity, supporting the involvement of Src-family kinase-sensitive signaling in this response. In mice, GsMTx4 significantly attenuated vascular permeability within minutes after reperfusion, consistent with the in vitro observations and supporting a role for mechanosensitive channel-associated signaling in ultra-acute blood-brain barrier leakage immediately after flow restoration.

    This study provides the first phosphoproteomic characterization of rapid phosphorylation changes associated with Piezo1 activation in human brain endothelial cells. Guided by these phosphoproteomic signatures, our data support the involvement of saracatinib-sensitive signaling, accompanied by occludin Tyr287 phosphorylation, in rapid endothelial barrier disruption. These findings suggest that Piezo1-associated signaling may contribute to ultra-acute BBB dysfunction and provide a rational for further investigation in the context of abrupt hemodynamic stress and cerebral revascularization.
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  • Early Onset of AbobotulinumtoxinA Effects in Post-Stroke Upper Limb Spasticity: A Prospective Observational Pilot Study.
    3 days ago
    Upper limb spasticity is a common complication of stroke that negatively affects motor function, range of motion, and quality of life. Although abobotulinumtoxinA is widely used for the treatment of focal post-stroke spasticity, evidence regarding its early onset of action remains limited. This prospective observational pilot study investigated the early clinical, functional, and neurophysiological effects of abobotulinumtoxinA in 20 adults with post-stroke upper limb spasticity. Patients received ultrasound-guided injections into the biceps brachii and flexor digitorum superficialis muscles and were evaluated at baseline, 24 h, 5 days, 7 days, 14 days, and 30 days after treatment. Outcome measures included the Modified Ashworth Scale (MAS), passive range of motion (ROM), caregiver-reported hand function assessed using a visual analog scale (VAS), and compound muscle action potential (cMAP) recordings. No significant changes were observed at 24 h. A significant reduction in spasticity was detected at the day-5 assessment, accompanied by significant improvements in ROM and functional outcomes. Neurophysiological assessment demonstrated significant reductions in cMAP amplitudes at the day-5 assessment, indicating early neuromuscular transmission blockade. Clinical improvements were also first detected at day-5 assessment and were maintained at subsequent evaluations through day 30. These findings indicate that clinically meaningful effects of abobotulinumtoxinA were detectable by the first scheduled assessment at day 5 after injection. Given the absence of intermediate assessments between 24 h and day 5, the exact timing of treatment onset cannot be determined. A multimodal assessment approach may help characterize early treatment-related changes and provide useful information for future studies investigating the timing of adjunctive rehabilitation interventions.
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  • Effect of Perinatal and Maternal Factors on Blood Pressure and Adiposity at Age 3.
    3 days ago
    The specific aim of the project was to evaluate the relationship between perinatal and maternal factors on childhood blood pressure (BP) and adiposity outcomes at Age 3. A retrospective case-control study of 128 children and their mothers enrolled in the Generations Project was completed to examine the association between different perinatal and maternal factors on childhood BP and adiposity outcomes at Age 3. The Generations Project of the Northwell Health System is a longitudinal, observational, population-based study following infants and their biological mothers. Using multivariable regression analysis, cesarean delivery (β = 0.07, CI = 0.04-0.10, p < 0.001) and small for gestational age (β = 0.07, CI = 0.002-0.13, p = 0.04) were individually associated with greater systolic blood pressure index during childhood. In adjusted regression analysis, IVF was associated with greater odds of elevated BP status (OR = 3.52, CI = 1.04-12.0, p = 0.04). Additionally, low birth weight (β = -0.86, CI = -1.64 to -0.08, p = 0.03) was associated with lower childhood body mass index Z-scores. It can be concluded that adverse perinatal and maternal conditions can create a suboptimal intrauterine environment that is ideal for immediate survival but can alter the trajectory of the developing fetus and lead to negative health consequences. This study builds upon the existing research examining the effect different perinatal and maternal conditions have on childhood health and expands on the limited research investigating the potential impact cesarean delivery and in vitro fertilization have on offspring BP and adiposity.
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  • Insights on Aortoenteric Fistulas from a Tertiary Referral Center: Diagnostic Algorithm, Management and Outcomes.
    3 days ago
    Background: Aortoenteric fistulas (AEFs) are uncommon emergency surgical conditions associated with high mortality. We explored the presentation and management of AEFs in a tertiary hospital in Qatar, a rapidly developing Middle Eastern country. By highlighting our institutional experience with ADFs and AOFs, we aim to contribute to the growing body of literature on this rare condition and to emphasize the importance of early diagnosis, appropriate surgical planning, and multidisciplinary care in optimizing patient outcomes. We also proposed a diagnostic classification of AEFs to better understand their location, relationship to the aorta, and pathology on both sides (the gastrointestinal tract and Aorta) for further studies. Methods: This was an observational, descriptive, retrospective, single-center case series that included 10 consecutive cases presenting with AEFs. We reviewed the clinical presentation, surgical management, and outcomes of AEF cases from 2008 to 2024. Data were extracted from electronic medical records and operative notes. Additionally, we reviewed the literature over the last two decades to summarize recently published English-language literature on aortoenteric fistulas (types, presentations, management and outcomes). Results: This observational case series included nine males and one female; four with aortoesophageal (AOF) and six with aortoduodenal (ADF) fistulas. The main presentations were hypotension and upper gastrointestinal bleeding. Blood cultures were positive in four cases, including Escherichia coli, Candida albicans, and Klebsiella. Foreign bodies were the underlying cause in two cases, while an old aortic coarctation repair was found in one case. Surgical repair was not completed in two patients who deteriorated quickly and died with hypovolemic shock. Two patients had thoracic endovascular aortic repair, and others had open surgeries. The overall AEF-related mortality was 60% (n = 6; open surgery group). Conclusions: This case series could support the importance of prompt diagnosis and multidisciplinary management. It also underscores the importance of individualized treatment to optimize survival. The proposed diagnostic algorithm still requires further evaluation and validation within large samples before its implementation on a large scale.
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