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Background Endovascular thrombectomy (EVT) has transformed acute ischemic stroke (AIS) care, with onset-to-puncture (OTP) time widely recognized as a critical determinant of outcome. However, emerging evidence suggests that in-hospital procedure time (PT)—from arterial puncture to final recanalization—may have an equally or more significant impact. This study examines the relative contribution of PT versus OTP to functional outcomes in patients with AIS undergoing EVT. Methods A retrospective analysis was conducted of 6644 patients with AIS treated at 44 international stroke centers from the Stroke Thrombectomy and Aneurysm Registry (STAR; 2016–2023). Multivariable regression, time-equivalence analysis, and marginal effects modeling were used to assess associations between PT, OTP, and 90-day modified Rankin Scale (mRS) outcomes. Centers were stratified by procedural efficiency and compared using propensity score matching (PSM). Mediation analysis evaluated whether PT accounted for inter-center differences. Results PT and OTP were independently associated with functional outcomes; however, PT had a significantly stronger effect (adjusted OR for mRS 0–2: PT=0.56 vs OTP=0.96 per hour). Each 5 min increase in PT was equivalent to 78–100 min of additional OTP in outcome impact. Centers with faster average PT had higher rates of functional independence (number needed to treat (NNT)=10), fewer complications, and lower symptomatic intracranial hemorrhage rates. PT significantly mediated the relationship between center tier and outcomes (Sobel’s P<0.001). Conclusion While minimizing OTP remains important, PT exerts a greater influence on outcomes after EVT. Procedural efficiency should be emphasized in stroke systems of care and included in center performance metrics to improve patient outcomes.

IntroductionBipolar disorder (BD) is a chronic illness that can lead to severe functioning impairment, which can disrupt daily life. This study aims to compare overall functioning and clinical presentation associated with early onset (EO) and mid-life onset (MO) BD.ObjectivesThe objective of this study is to be able to predict the cognitive and functional impairment evolution of bipolar disorder based on the onset.MethodsA total of 154 BD patients (81 in euthymia and 51 in a depressive episode) participated in this cross-sectional study. We selected two groups of subjects based on age at onset of the first mood episode (EO: 0-20 years, n=117; MO: 20-40 years, n=37) and compared socio-demographic, clinical variables and functional impairment assessed by the World Health Organization Disability Assessment Schedule (WHODAS 2.0).Results75.2% of the patients with an EO were female, they had higher psychiatric comorbidities prevalence (76.1% vs. 43.2%; p<.001), being personality disorders the most significant (30.2% vs. 5.4%; p=.001), more suicide attempts (51.3% vs. 16.2%; p<.001), mood episodes (mdn=12, iqr=17 vs. mdn=6, iqr=9.5; p=.001), childhood abuse (93.5% vs. 73.9%; p=.014), being verbal (78.0% vs. 52.2%; p=.015) and physical abuse (51.6% vs. 21.7%; p=.009) higher compared to MO. Functionality was also affected, with higher dysfunction percentages in EO (mdn=47, iqr=34.7 vs. mdn=24, iqr=12.5; p<.001) affecting cognition (mdn=8.5, iqr=6 vs. mdn=4, iqr=7; p<.001), self-care (mdn=2, iqr=5 vs. mdn=0, iqr=1; p<.001), daily activities (mdn=12, iqr=13 vs. mdn=4, iqr=10; p<.001) and community participation (mdn=13, iqr=8.7 vs. mdn=8, iqr=7; p<.001).EO depressed patients (n=38; F: 30; M: 8), had more personality disorders (42.1% vs. 0%; p=.010), suicide attempts (60.5% vs. 0%; p<.001), mood episodes (mdn=12, iqr=12 vs. mdn=5.5, iqr=4.7; p=.001), lower overall functionality (mdn=57, iqr=41.5 vs. mdn=35, iqr=38.3; p=.009), cognition (mdn=10, iqr=6.5 vs. mdn=4, iqr=9; p=.023), self-care (mdn=4, iqr=6.2 vs. mdn=0, iqr=3; p=.008), oneself care (mdn=9, iqr =7 vs. mdn=5, iqr=8.5; p=.025), daily activities (mdn=15.5, iqr=14 vs. mdn=11, iqr=12.7; p=.037) and community participation (mdn= 15.5, iqr=8.2 vs. mdn=11.5, iqr=5.7; p=.030).EO euthymic patients (n=59; F: 42; M: 17) had more psychiatric comorbidities (74.6% vs. 33.3%; p=.001), physical abuse history (51.2% vs. 0%; p= .002), and lower functionality (mdn=7, iqr=7 vs. mdn=2, iqr=7; p=.004), cognition (mdn=7.5, iqr=7 vs. mdn=4, iqr=7; p=.033), daily activities (mdn=9, iqr=11 vs. mdn=3, iqr=8.5; p=.005) and community participation (mdn=10, iqr=9 vs. mdn= 7, iqr=7; p=.031).ConclusionsResults suggest that patients with an EO are more associated with severe psychosocial functioning impairment. Future studies are needed to clarify a more severe illness prediction between EO and MO.Disclosure of InterestNone Declared

ABSTRACT Objectives To explore the clinical impact of social determinants of health (SDoH) stress in bipolar disorder (BD) course of illness and to explore potential gender differences in SDoH stress endorsement. Methods 2280 individuals living with BD type I or II (62% women; 67.5% BD‐I) participating in the Mayo Clinic Bipolar Biobank who completed a questionnaire assessing positive and negative‐valent stressors in the 12 months prior to study enrollment were included for this analysis. Six negative stressors were used as proxies of SDoH. Generalized linear models were used to test the association between SDoH stressors and markers of illness severity as well as potential differences by sex by including an interaction term. Results After adjusting for age, sex, and recruitment site, SDoH‐related stressors were significantly associated with a more severe course of illness in both men and women. Except for unemployment rates, women reported more frequently SDoH‐related stress (i.e., lack of family support, financial problems, health coverage and access problems). Conclusions The study found significant gender differences in both the endorsement of specific SDoH stressors and in the prevalence of specific illness severity markers; however, it did not directly test the predictive relationship between gender differences in SDoH and illness severity markers. Future studies aiming to achieve health equity in mental health care should continue assessing social determinants of health stressors, incorporating a gender perspective to better understand their influence on bipolar disorder.

Introduction: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear. Patients and methods: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in the Stroke Thrombectomy and Aneurysm Registry. Patients selected for EVT by advanced imaging (CTP or MR) were matched with those selected by conventional imaging using propensity score matching (PSM) accounting for possible confounders. Primary outcome was functional independence at 90 days. Other outcomes include bedridden state or death at 90-days and symptomatic intracranial hemorrhage (sICH). Results: 268 patients were included. 150 patients were selected for BAO EVT by conventional imaging, 86 by CTP, and 32 by MR. Patients selected by advanced imaging were significantly older than those selected by conventional imaging (median age 71 vs 64 years, p = 0.001); patient characteristics were otherwise similar between cohorts. After PSM, 90-day outcomes were similar between the two cohorts ( p = 0.56), with similar rates of functional independence (39.4% vs 35.1%, p = 0.65), bedridden state or death (40.4% vs 44.7%, p = 0.66), and sICH (3.3% vs 5.7%, p = 0.49) for conventional and advanced imaging groups, respectively. Results were similar across treatment time windows (all p > 0.05). Conclusions: Selecting patients for basilar EVT using conventional versus advanced imaging did not result in different clinical outcomes, regardless of treatment time windows. Conventional imaging appears sufficient as a first-line tool for selecting basilar EVT patients in routine clinical practice.

Background and objectives Arteriovenous malformations (AVMs) with perinidal aneurysms and single draining vein are associated with an elevated risk of rupture and increased procedural complexity. The role of preoperative embolization in this high-risk anatomical subset remains unclear. This study aimed to evaluate the safety and efficacy of microsurgery with preoperative embolization, compared with microsurgery alone in patients with such AVMs. Methods We conducted a multicenter retrospective analysis of an AVM registry from the MISTA (Multicenter International Study for Treatment of Brain AVMs) consortium and included AVMs with perinidal aneurysms and a single draining vein. Baseline characteristics, angiographic outcomes, functional outcomes, and complication rates were compared. Propensity score weighting (PSW) using the covariate balancing method was applied to adjust for baseline differences. Results Out of a total of 1919 patients, 65 met the inclusion criteria; 45 patients underwent preoperative embolization followed by microsurgery, and 20 underwent microsurgery alone. After adjustment, complete obliteration rates were similar between groups (OR 0.87, 95% CI 0.04 to 16.33, P=0.92), as were rates of functional independence at discharge and follow-up. Overall complication, symptomatic complication, and mortality rates did not differ significantly between groups. However, permanent complications were significantly lower in patients with preoperative embolization (OR 0.06, 95% CI 0.004 to 0.84, P=0.03). Discussion In patients with AVMs featuring perinidal aneurysms and single draining vein, preoperative embolization followed by microsurgery was associated with fewer permanent complications and no increase in adverse outcomes compared with microsurgery alone. However, given the small number of events, this finding should be interpreted cautiously.

Abstract Background: Responsiveness to mood-stabilizing pharmacotherapy varies in bipolar disorder (BD). We investigated clinical correlates of second-generation antipsychotic (SGA) treatment response and conducted the first genome-wide association study (GWAS), including exploratory polygenic scores (PGS), of SGA pharmacogenomic treatment response in BD. Methods: Treatment response was quantified using the Alda scale, and GWAS was performed using Alda-A score, controlling for sex, genotyping batch, and the genomic principal components. Results: The cohort included 2,159 adults with BD (1,416 BD-I, 691 BD-II, 51 schizoaffective BD), mean age 41.8 years, 62% female, 84% white, and 14% Hispanic. Nearly half (48%) were treated with SGAs. Current SGA users were younger (41.2±14.7 vs. 42.5±15.3 years, p =0.040), more likely to be Hispanic (14% vs. 11%, p =0.047), had a higher body mass index (BMI; 30.4±7.6 vs. 29.5±7.1 kg/m 2 , p =0.005). Lifetime comorbidity patterns for current SGA users include higher rates of manic psychosis (29% vs. 17%, p <0.001) and eating disorders — Anorexia Nervosa (7% vs. 4%, p =0.003), Bulimia Nervosa (7% vs. 4%, p =0.003), and Binge Eating Disorder (14% vs. 11%, p =0.030). We detected a genome-wide significant association between SGA Alda-A scores and GAS7 variants (top variant: rs202127418, β =-2.998, p =4.96E-08). However, SGA response was not significantly associated with PGS for schizophrenia, BD, and major depression (FDR>0.05). Conclusions: SGAs are frequently utilized as mood stabilizers in patients with BD and are associated with manic psychosis and eating disorders. GAS7 variants may predict SGA response, but larger, more diverse cohorts are needed for validation.

OBJECTIVE Mechanical thrombectomy (MT) is well established for large-vessel occlusion (LVO) strokes, but its safety in distal and medium-vessel occlusions (DMVOs) requires further investigation. This study analyzed the relationship between procedural approaches, petechial hemorrhage (PetH), and clinical outcomes in DMVO thrombectomy, with particular attention to technical considerations and the complex interplay between tissue injury and hemorrhagic complications. METHODS A retrospective cohort study was conducted on DMVO stroke patients treated with MT at 37 stroke centers worldwide from 2016 to 2024. Patients were categorized based on follow-up imaging into those with or without PetH. Four logistic regression models analyzed the association of PetH with favorable functional outcomes (modified Rankin Scale score ≤ 2) at 90 days, early neurological improvement (≥ 4-point National Institutes of Health Stroke Scale score decrease at 24 hours), all-cause mortality, and independent determinants of PetH. Adjusted odds ratios (aORs), 95% confidence intervals, and p values were reported. RESULTS Of 1428 patients, 439 (30.7%) developed PetH. Factors independently associated with PetH were multiple thrombectomy passes (aOR 1.58, 95% CI 1.21–2.06; p = 0.001), IV thrombolysis (aOR 1.31, 95% CI 1.01–1.69; p = 0.04), and the combined use of a stent retriever with aspiration as the first-line method compared with aspiration alone (aOR 1.66, 95% CI 1.15–2.38; p = 0.007). Conversely, general anesthesia (aOR 0.55, 95% CI 0.40–0.77; p < 0.001), higher Alberta Stroke Program Early CT Scores (aOR 0.76, 95% CI 0.69–0.83; p < 0.001), and successful recanalization (aOR 0.56, 95% CI 0.39–0.80; p = 0.002) were significantly associated with a lower odds of PetH. PetH was associated with a decreased odds of favorable functional outcomes (aOR 0.51, 95% CI 0.36–0.73; p < 0.001), reduced early neurological improvement (aOR 0.59, 95% CI 0.44–0.79; p < 0.001), and increased all-cause mortality (aOR 1.84, 95% CI 1.23–2.76; p < 0.001). CONCLUSIONS PetH is a frequent sequela following MT in DMVO strokes and is associated with poorer outcomes, likely reflecting underlying ischemic injury rather than direct causation. Procedural factors influence PetH risk, suggesting medical treatment as first-line therapy for DMVOs, with MT reserved for refractory cases using less aggressive approaches.

ABSTRACT Bipolar disorder’s (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in neither subtype. Unipolar mania aligned with psychosis over internalizing, and was distinguishable from BD1, and rapid cycling showed heritable cross-domain liability. We identified 356 risk loci, 158 novel, including the first univariate-GWAS associations for psychosis, unipolar mania, rapid cycling and schizoaffective disorder—and 249 credible genes (89 high-confidence), 12 with approved-drug or clinical-phase annotations. Cell-type association showed a midbrain dopaminergic–GABAergic gradient along the psychotic factor. BD’s genetic architecture appears hierarchical—a general liability resolving into dimensions of course and comorbidity beyond diagnostic subtypes.

Background The effectiveness of endovascular thrombectomy (EVT) for low Alberta Stroke Program Early CT score (ASPECTS) stroke patients with occlusion of the second segment of the middle cerebral artery (M2) is unclear. Methods This was a multicenter retrospective study. Patients with M1 or M2 occlusions and low ASPECTS (<6) who underwent successful EVT (modified treatment in cerebral ischemia score of 2b or higher) were included. Primary outcome was futile EVT reperfusion (defined as 90-day modified Rankin scale of 5 or 6). Other outcomes of interest include acceptable outcomes (modified Rankin scale of 3 or less) and intracranial hemorrhage (ICH), and all-cause 90-day mortality. Outcomes for M1 patients were compared to M2 patients with multivariable logistic regression models accounting for potential confounders. Results 173 patients with M1 or M2 occlusions and low ASPECTS (<6) who underwent successful EVT were identified. After multivariable adjustments, M2 patients had significantly higher odds of futile reperfusion (OR 5.48 [95%CI 1.91 to 15.7], p = 0.002), lower odds of acceptable outcomes (OR 0.33 [95%CI 0.12 to 0.89], p = 0.028), and higher odds of all-cause mortality (OR 4.90 [95%CI 1.65 to 14.5], p = 0.004). These findings suggest that EVT's efficacy for low-ASPECTS stroke patients may be diminished for patients with M2 occlusions. M2 occlusion was not significantly associated with ICH. Conclusions Among low-ASEPCTS stroke patients who underwent successful EVT, those with M2 occlusions had significantly higher odds of poor outcome compared to those with M1 occlusions.