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Objective To evaluate the effect of procedure time on thrombectomy outcomes in different subpopulations of patients undergoing endovascular thrombectomy (EVT), given the recently expanded indications for EVT. Methods This multicenter study included patients undergoing EVT for acute ischemic stroke at 35 centers globally. Procedure time was defined as time from groin puncture to successful recanalization (Thrombolysis in Cerebral Infarction score ≥2b) or abortion of procedure. Patients were stratified based on stroke location, use of IV tissue plasminogen activator (tPA), Alberta Stroke Program Early CT score, age group, and onset-to-groin time. Primary outcome was the 90-day modified Rankin Scale (mRS) score, with scores 0-2 designating good outcome. Secondary outcome was postprocedural symptomatic intracranial hemorrhage (sICH). Multivariate analyses were performed using generalized linear models to study the impact of procedure time on outcomes in each subpopulation. results Among 8961 patients included in the study, a longer procedure time was associated with higher odds of poor outcome (mRS score 3-6), with 10% increase in odds for each 10 min increment. When procedure time exceeded the 'golden hour', poor outcome was twice as likely. The golden hour effect was consistent in patients with anterior and posterior circulation strokes, proximal or distal occlusions, in patients with large core infarcts, with or without IV tPA treatment, and across age groups. Procedures exceeding 1 hour were associated with a 40% higher sICH rate. Posterior circulation strokes, delayed presentation, and old age were the variables most sensitive to procedure time. Conclusions In this work we demonstrate the universality of the golden hour effect, in which procedures lasting more than 1 hour are associated with worse clinical outcomes and higher rates of sICH across different subpopulations of patients undergoing EVT. [ABSTRACT FROM AUTHOR]

Background: Endovascular thrombectomy(EVT) is the standard of care for large vessel occlusion(LVO) stroke. Data on technical and clinical outcome in proximal medium vessel occlusions(pMeVOs) comparing frontline techniques remain limited. Methods: We report an international multicenter retrospective study of patients undergoing EVT for stroke at 32 centers between 2015–2021. Patients were divided into LVOs(ICA/M1/Vertebrobasilar) or pMeVOs(M2/A1/P1) and categorized by thrombectomy technique. Primary outcome was 90-day good functional outcome(mRS ≤ 2). Multivariate logistic regressions were used to evaluate the impact of technical variables on clinical outcomes. Propensity score matching was used to compare outcome in patients with pMeVO treated with aspiration versus stent-retriever. Results: In the cohort of 5977 LVO and 1287 pMeVO patients, pMeVO did not independently predict good-outcome(p = 0.55). In pMeVO patients, successful recanalization irrespective of frontline technique(aOR = 3.2,p < 0.05), procedure time ≤ 1-h(aOR = 2.2,p < 0.05), and thrombectomy attempts ≤ 4(aOR = 2.8,p < 0.05) were independent predictors of good-outcomes. In a propensity-matched cohort of aspiration versus stent-retriever pMeVO patients, there was no difference in good-outcomes. The rates of hemorrhage were higher(9%vs.4%,p < 0.01) and procedure time longer(51-min vs. 33-min,p < 0.01) with stent-retriever, while the number of attempts was higher with aspiration(2.5vs.2,p < 0.01). Rates of hemorrhage and good-outcome showed an exponential relationship to procedural metrics, and were more dependent on time in the aspiration group compared to attempts in the stent-retriever group. Conclusions: Clinical outcomes following EVT for pMeVO are comparable to those in LVOs. The golden hour or 3-pass rules in LVO thrombectomy still apply to pMeVO thrombectomy. Different techniques may exhibit different futility metrics; SR thrombectomy was more influenced by attempts whereas aspiration was more dependent on procedure time. [ABSTRACT FROM AUTHOR]

Background Recent clinical trials have shown that mechanical thrombectomy is superior to medical management for large vessel occlusion for up to 24 hours from onset. Our objective is to examine the safety and efficacy of thrombectomy beyond the standard of care window. Methods A retrospective review was undertaken of the multicenter Stroke Thrombectomy and Aneurysm Registry (STAR). We identified patients who underwent mechanical thrombectomy for large vessel occlusion beyond 24 hours. We selected a matched control group from patients who underwent thrombectomy in the 6-24-hour window. We used functional independence at 3 months as our primary outcome measure. results We identified 121 patients who underwent thrombectomy beyond 24 hours and 1824 in the 6-24-hour window. We selected a 2:1 matched group of patients with thrombectomy 6-24 hours as a comparison group. Patients undergoing thrombectomy beyond 24 hours were less likely to be independent at 90 days (18 (18.8%) vs 73 (34.9%), P=0.005). They had higher odds of mortality at 90 days in the adjusted analysis (OR 2.34, P=0.023). Symptomatic intracerebral hemorrhage and other complications were similar in the two groups. In a multivariate analysis only lower number of attempts was associated with good outcomes (OR 0.27, P=0.022). Conclusions Mechanical thrombectomy beyond 24 hours appears to be safe and tolerable with no more hemorrhages or complications compared with standard of care thrombectomy. Outcomes and mortality in this time window are worse compared with an earlier time window, but the rates of good outcomes may justify this therapy in selected patients. [ABSTRACT FROM AUTHOR]

Background Reducing intracranial hemorrhage (ICH) can improve patient outcome in acute ischemic stroke (AIS) intervention. We sought to identify ICH risk factors after AIS thrombectomy. Methods This is a retrospective review of the Stroke Thrombectomy and Aneurysm Registry (STAR) database. All patients who underwent AIS thrombectomy with available ICH data were included. Multivariable regression models were developed to identify predictors of ICH after thrombectomy. Subgroup analyses were performed stratified by symptom status and European Cooperative Acute Stroke Study (ECASS) grade. Results The study cohort comprised 6860 patients. Any ICH and symptomatic ICH (sICH) occurred in 25% and 7% of patients, respectively. Hemorrhagic infarction 1 (HI1) occurred in 36%, HI2 in 24%, parenchymal hemorrhage 1 (PH1) in 22%, and PH2 in 17% of patients classified by ECASS grade. Intraprocedural complications independently predicted any ICH (OR 3.8083, P<0.0001), PH1 (OR 1.9053, P=0.0195), and PH2 (OR 2.7347, P=0.0004). Race also independently predicted any ICH (black: OR 0.5180, P=0.0017; Hispanic: OR 0.4615, P=0.0148), sICH (non- white: OR 0.4349, P=0.0107), PH1 (non-white: OR 3.1668, P<0.0001), and PH2 (non- white: OR 1.8689, P=0.0176), with white as the reference. Primary mechanical thrombectomy technique also independently predicted ICH. ADAPT (A Direct Aspiration First Pass Technique) was a negative predictor of sICH (OR 0.2501, P<0.0001), with stent retriever as the reference. Conclusions This study identified ICH risk factors after AIS thrombectomy using real-world data. There was a propensity towards a reduced sICH risk with direct aspiration. Procedural complications and ethnicity were predictors congruent between categories of any ICH, sICH, PH1, and PH2. Further investigation of technique and ethnicity effects on ICH and outcomes after AIS thrombectomy is warranted. [ABSTRACT FROM AUTHOR]

Background Endovascular thrombectomy (EVT) is the standard-of-care for proximal large vessel occlusion (LVO) stroke. Data on technical and clinical outcomes in distal vessel occlusions (DVOs) remain limited. Methods This was a retrospective study of patients undergoing EVT for stroke at 32 international centers. Patients were divided into LVOs (internal carotid artery/M1/vertebrobasilar), medium vessel occlusions (M2/A1/P1) and isolated DVOs (M3/M4/A2/A3/P2/P3) and categorized by thrombectomy technique. Primary outcome was a good functional outcome (modified Rankin Scale ≤2) at 90 days. Secondary outcomes included recanalization, procedure-time, thrombectomy attempts, hemorrhage, and mortality. Multivariate logistic regressions were used to evaluate the impact of technical variables. Propensity score matching was used to compare outcome in patients with DVO treated with aspiration versus stent retriever Results We included 7477 patients including 213 DVOs. Distal location did not independently predict good functional outcome at 90 days compared with proximal (p=0.467). In distal occlusions, successful recanalization was an independent predictor of good outcome (adjusted odds ratio (aOR) 5.11, p<0.05) irrespective of technique. Younger age, bridging therapy, and lower admission National Institutes of Health Stroke Scale (NIHSS) were also predictors of good outcome. Procedure time ≤1 hour or ≤3 thrombectomy attempts were independent predictors of good outcomes in DVOs irrespective of technique (aOR 4.5 and 2.3, respectively, p<0.05). There were no differences in outcomes in a DVO matched cohort of aspiration versus stent retriever. Rates of hemorrhage and good outcome showed an exponential relationship to procedural metrics, and were more dependent on time in the aspiration group and attempts in the stent retriever group. Conclusions Outcomes following EVT for DVO are comparable to LVO with similar results between techniques. Techniques may exhibit different futility metrics; stent retriever thrombectomy was influenced by attempts whereas aspiration was more dependent on procedure time. [ABSTRACT FROM AUTHOR]

Background: The duration of mechanical thrombectomy (MT) is a negative predictor of outcomes in acute ischemic stroke (AIS), yet the precise mechanisms are unclear. We investigated whether the placement of large-bore catheters intracranially reduces blood flow to the ischemic penumbra and diminishes the efficacy of MT., Methods: We investigated the impact of different catheter sizes on flow through the intracranial circulation using an in vitro model. Data from a multicenter international registry of AIS patients undergoing MT between January 2016 and December 2023 were reviewed. Intracranial procedure time (icPT) from catheter placement to thrombectomy completion was analyzed using propensity score (PS) matched analysis of patients with successful recanalization achieved in <30 min versus ≥30 min (n=1006/group). Primary outcome was modified Rankin Scale (mRS) score at 90 days (mRS 0-2 favorable). Secondary outcomes included mortality, symptomatic intracranial hemorrhage (sICH), and need for craniectomy., Results: Using our flow model, we demonstrated a significant reduction in middle cerebral artery and anterior cerebral artery blood flow with the use of larger caliber catheters in the internal carotid artery. Controlling for covariates in 3318 patients, longer icPT predicted lower odds of 90-day favorable outcome (adjusted odds ratio (aOR) 0.87, P<0.01), increased mortality (aOR 1.03, P<0.01), higher decompressive craniectomy rates (aOR 1.07, P<0.01), and increased sICH (aOR 1.07, P<0.01). Each additional 10 mins of icPT correlated with a 13% decrease in recanalization success. The impact of icPT on outcomes was consistent regardless of recanalization success, though catheter size influenced effects. Reduced intraprocedural blood pressure worsened icPT's effects., Conclusions: This study is the first to demonstrate the risks associated with the duration of catheter use during MT and to propose strategies to mitigate these risks in AIS., Competing Interests: Competing interests: Sami Al Kasab: Grant from Stryker for RESCUE-ICAS registry. Adam Arthur: Consultant for Arsenal, Balt, Johnson and Johnson, Medtronic, Microvention, Penumbra, Perfuze, Scientia, Siemens, Stryker. Research support from Balt, Medtronic, Microvention, Penumbra, Siemens. Shareholder in several companies. Shinichi Yoshimura: Lecture fee from Stryker, Medtronic, Johnson & Johnson, Kaneka Medics. Min Park: Consultant for Medtronic. Waleed Brinjikji: Equity, royalties, consulting fees, and leadership roles in several companies including Medtronic, Stryker, and others. Charles Matouk: Consultant for Stryker, Medtronic, Microvention, Penumbra, and Silk Road Medical. Speaker for Penumbra and Silk Road Medical. Daniele Romano: Consultant for Penumbra, Balt, Microvention, Phenox. David J Altschul: Consultant for MicroVention, Stryker, and Cerenovus. Richard Williamson: Consultant for Medtronic, Stryker, and Synaptive Medical. Reade De Leacy: Research grants, consultant roles, and minor equity interest in several companies. Mohamad Ezzeldin: Speaker for Viz.ai and stocks in Galaxy Therapeutics. Peter Kan: Grants, consulting roles, stock ownership in several companies. Michael Levitt: Grants, consulting agreements, equity interests in several companies. Jonathan A Grossberg: Grant support and consulting roles in several entities. Alejandro M Spiotta: Research support from Penumbra, Microvention, Medtronic, Stryker, RapidAI, Brain Aneurysm Foundation. Consultant for Penumbra, Terumo, and RapidAI. Other authors: No conflict of interest., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Neuronal activity in the nucleus accumbens core (NAcore) is necessary for reward-seeking behaviors. We hypothesized that the differential encoding of natural and drug rewards in the NAcore contributes to substance use disorder. We leveraged single-cell calcium imaging of dopamine D1- and D2-receptor-expressing medium spiny neurons (MSNs) in the NAcore of mice to examine differences between sucrose and cocaine rewarded (self-administration) and unrewarded (abstinent and cue-induced) seeking. Activity was time-locked to nose-poking for reward, clustered, and compared between sucrose and cocaine. Only in cocaine-trained mice were excited D1-MSNs securely stable, capable of decoding nose-poking in all rewarded and unrewarded sessions and correlated with the intensity of nose-poking for unrewarded seeking. Furthermore, D1-MSNs formed a stable ensemble predictive of seeking behavior after extended cocaine, but not sucrose abstinence. The excited D1-MSN ensemble uniquely drives cue-induced cocaine seeking and may contribute to why drug seeking is prepotent over natural reward seeking in cocaine use disorder., Competing Interests: Declaration of Interests: the authors declare no competing interests.

Objective: The behavioral and diagnostic heterogeneity within human opioid use disorder (OUD) diagnosis is not readily captured in current animal models, limiting translational relevance of the mechanistic research that is conducted in experimental animals. We hypothesize that a non-linear clustering of OUD-like behavioral traits will capture population heterogeneity and yield subpopulations of OUD vulnerable rats with distinct behavioral and neurocircuit profiles., Methods: Over 900 male and female heterogeneous stock rats, a line capturing genetic and behavioral heterogeneity present in humans, were assessed for several measures of heroin use and rewarded and non-rewarded seeking behaviors. Using a non-linear stochastic block model clustering analysis, rats were assigned to OUD vulnerable, intermediate and resilient clusters. Additional behavioral tests and circuit analyses using c-fos protein activation were conducted on the vulnerable and resilient subpopulations., Results: OUD vulnerable rats exhibited greater heroin taking and seeking behaviors relative to those in the intermediate and resilient clusters. Akin to human OUD diagnosis, further vulnerable rat sub-clustering revealed subpopulations with different combinations of behavioral traits, including sex differences. Lastly, heroin cue-induced neuronal patterns of circuit activation differed between resilient and vulnerable phenotypes. Behavioral sex differences were recapitulated in patterns of circuitry activation, including males preferentially engaging extended amygdala stress circuitry, and females cortico-striatal drug cue-seeking circuitry., Conclusion: Using a non-linear clustering approach in rats, we captured behavioral diagnostic heterogeneity reflective of human OUD diagnosis. OUD vulnerability and resiliency were associated with distinct neuronal activation patterns, posing this approach as a translational tool in assessing neurobiological mechanisms underpinning OUD.