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Objective: About 25% of patients with acute ischemic stroke (AIS) present within the intravenous thrombolytic (IVT) therapeutic window of <4.5 h. This study is to elucidate the safety and efficacy of IVT in the extended therapeutic window (ETW) in patients with AIS., Methods: Using PRISMA guidelines, a systematic review was conducted using PubMed, Embase, and Scopus. A rigorous risk of bias assessment was conducted using the RoB2 tool. Rates of excellent and good functional outcome (mRS 0-1 and mRS 0-2) at 90 days, symptomatic intracranial hemorrhage (sICH), and mortality at 90 days were pooled using generalized linear mixed model and compared with controls. Meta-analyses were conducted employing random-effect models with risk ratio (RR) and 95% confidence intervals (CIs). Subgroup analysis was performed to assess the effect of imaging modalities used for patient selection., Results: Eight randomized controlled trials (n = 2221, 59% male) were included. At 90 days IVT showed higher rates of functional recovery: mRS 0-1: RR 1.21 95% CI 1.1-1.34, p < 0.001, and mRS 0-2: RR 1.11 95% CI 1.03-1.18, p = 0.004. Rate of mortality at 90 day was not different between groups: RR 1.17 95% CI 0.93-1.48, p = 0.17. However, the rate of sICH was higher among IVT group: RR 2.93 95% CI 1.53-5.6, p = 0.001. Subgroup analysis showed higher mRS 0-1 among patients who were selected based on perfusion imaging (p < 0.05)., Interpretation: The use of IVT in AIS in ETW is beneficial especially with the use of perfusion imaging for patients' selection., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood., Methods: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, and hemorrhagic complications., Results: Of the patients, 223 (34%) were on anticoagulation therapy. Anticoagulated patients were older (median age 78 vs 74 years; p  < 0.001) and had a higher prevalence of atrial fibrillation (77% vs 26%; p  < 0.001). Their baseline National Institutes of Health Stroke Scale (NIHSS) scores were also higher (median 12 vs 9; p  = 0.002). Before propensity score matching (PSM), anticoagulated patients had similar rates of favorable 90-day outcomes (mRS 0-1: 30% vs 37%, p  = 0.1; mRS 0-2: 47% vs 50%, p  = 0.41) but higher mortality (26% vs 17%, p  = 0.008). After PSM, there were no significant differences in outcomes between the two groups., Conclusion: Anticoagulated patients undergoing MT for AIS due to DMVO did not show significant differences in 90-day mRS outcomes, reperfusion, or hemorrhage compared to non-anticoagulated patients after adjustment for covariates., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation.Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work.Dr. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board); all not directly related to the present work.Dr. Henninger received support from W81XWH-19-PRARP-RPA form the CDMRP/DoD, NS131756 and U24NS113844 from the NINDS, and NR020231 from the NINR and received compensation from Myrobalan, Inc. and General Dynamics during the conduct of this study unrelated to this work.Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical.Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work.Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra.Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson and Phenox (paid lectures), all not directly related to the present work.Dr. Puri is a consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc and Arsenal Medical, he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular and Stryker Neurovascular, and holds stocks in InNeuroCo, Agile, Perfuze, Galaxy and NTI.Dr. Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally).Dr. Jabbour is a consultant for Medtronic, Microvention and Cerus.

Background: Acute ischemic stroke (AIS) from primary medium vessel occlusions (MeVO) is a prevalent condition associated with substantial morbidity and mortality. Despite the common use of mechanical thrombectomy (MT) in AIS, predictors of poor outcomes in MeVO remain poorly characterized., Methods: In this prospectively collected, retrospectively reviewed, multicenter, multinational study, data from the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry were analyzed. The study included 1568 patients from 37 academic centers across North America, Asia, and Europe, treated with MT, with or without intravenous tissue plasminogen activator (IVtPA), between September 2017 and July 2021., Results: Among the 1568 patients, 347 (22.2%) experienced very poor outcomes (modified Rankin score (mRS), 5-6). Key predictors of poor outcomes were advanced age (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.02 to 1.04; p < 0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR: 1.07; 95% CI: 1.05 to 1.10; p < 0.001), pre-operative glucose levels (OR: 1.01; 95% CI: 1.00 to 1.02; p < 0.001), and a baseline mRS of 4 (OR: 2.69; 95% CI: 1.25 to 5.82; p = 0.011). The multivariable model demonstrated good predictive accuracy with an area under the receiver-operating characteristic (ROC) curve of 0.76., Conclusions: This study demonstrates that advanced age, higher NIHSS scores, elevated pre-stroke mRS, and pre-operative glucose levels significantly predict very poor outcomes in AIS-MeVO patients who received MT. These findings highlight the importance of a comprehensive risk assessment in primary MeVO patients for personalized treatment strategies. However, they also suggest a need for cautious patient selection for endovascular thrombectomy. Further prospective studies are needed to confirm these findings and explore targeted therapeutic interventions., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. Dr Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading), and Artedrone (Board); all not directly related to the present work. Dr Henninger received support from CDMRP/DoD W81XWH-19-PRARP-RPA and NINDS NS131756, during the conduct of the study. Dr Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, and Rapid Medical. Dr Yeo reports Advisory work for AstraZeneca, substantial support from NMRC Singapore, and is a medical advisor for See-mode, Cortiro, and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. Dr Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. Dr Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson, and Phenox (paid lectures), all not directly related to the present work. Dr Puri is a consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc, and Arsenal Medical; he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular, and Stryker Neurovascular; and he holds stocks in InNeuroCo, Agile, Perfuze, Galaxy, and NTI. Dr Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally). Dr Jabbour is a consultant for Medtronic, Microvention, and Cerus.

Background: Heparin may be administered during mechanical thrombectomy (MT) for acute ischemic stroke due to large vessel occlusions (AIS-LVO), with the aim of enhancing reperfusion and improving patient outcomes. The uncertain balance between risks and benefits of administering heparin during MT prompted us to perform this systematic review and meta-analysis., Methods: A comprehensive search was conducted in PubMed, Embase, and Scopus to find studies that report the safety or efficacy of administering heparin during MT for AIS-LVO. Meta-analysis was performed using the random effects model. In case of significant heterogeneity a subgroup analysis was performed., Results: From 2398 screened records, we included 15 studies. Rate of favorable functional outcome (90 day modified Rankin Scale 0-2 (mRS 0-2)) was lower among patients who received heparin (OR, 0.88 [95 %CI 0.79-0.98]; p=.023). Risk of distal embolization was higher in patients who received heparin (OR, 1.25 [95 %CI 1.01-1.55]; p=.04). The subgroup analysis showed that patients who received intravenous thrombolysis (IVT) had higher risk of Symptomatic intracranial hemorrhage (sICH) (OR, 2.94 [95 %CI 1.30-6.63]; p=.009) and lower rate of mRS 0-2 (OR, 0.66 [95 %CI 0.50-0.87]; p=.004). Heparin use didn't affect successful reperfusion rate (Thrombolysis in cerebral infarction ≥2B), mortality or any ICH risk., Conclusion: Overall, our analysis indicates that administering heparin during MT for AIS-LVO correlates with worse clinical outcomes and increased distal embolization rates. Moreover, it is linked to a higher risk of sICH in patients who receive IVT. Consequently, the routine utilization of heparin during MT should be reconsidered., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objectives: Ischemic stroke, a leading cause of mortality, necessitates understanding its mechanism for effective prevention. Echocardiography, especially transesophageal echocardiography (TEE), is the gold standard for detection of cardiac sources of stroke including left atrial thrombus, although its invasiveness, operator skill dependence, and limited availability in some centers prompt exploration of alternatives, such as cardiac CT (CCT). We conducted a systematic review and meta-analysis assessing the ability of CCT in the detection of intracardiac thrombus compared with echocardiography., Methods: We searched 4 databases up through September 8, 2023. Major search terms included a combination of the terms "echocardiograph," "CT," "TEE," "imaging," "stroke," "undetermined," and "cryptogenic." The current systematic literature review of the English language literature was reported in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. We assessed risk of bias using the QUADAS-2 tool and used random-effects meta-analysis to calculate different diagnostic metrics., Results: The meta-analysis investigating CCT vs echocardiography for intracardiac thrombus detection yielded a total of 43 studies of 9,552 patients. Risk-of-bias assessment revealed a predominantly low risk of bias in the flow and timing, index test, and patient selection domains and a predominantly unclear risk of bias in the reference standard domain. The analysis revealed an overall sensitivity of 98.38% (95% CI 89.2-99.78) and specificity of 96.0% (95% CI 92.55-97.88). Subgroup analyses demonstrated that delayed-phase, electrocardiogram-gated CCT had the highest sensitivity (100%; 95% CI 0-100) while early-phase, nongated CCT exhibited a sensitivity of 94.31% (95% CI 28.58-99.85). The diagnostic odds ratio was 98.59 (95% CI 44.05-220.69). Heterogeneity was observed, particularly in specificity and diagnostic odds ratio estimates., Discussion: CCT demonstrates high sensitivity, specificity, and diagnostic odds ratios in detecting intracardiac thrombus compared with traditional echocardiography. Limitations include the lack of randomized controlled studies, and other cardioembolic sources of stroke such as valvular disease, cardiac function, and aortic arch disease were not examined in our analysis. Large-scale studies are warranted to further evaluate CCT as a promising alternative for identifying intracardiac thrombus and other sources of cardioembolic stroke.

Background: The effective treatment for patients with acute ischemic stroke (AIS) with cervical internal carotid pseudo-occlusion (cICA-PO) requires comprehensive research on the safety and outcomes of endovascular thrombectomy (EVT). However, there are limited data available, highlighting the need for further research to ensure better treatment strategies and improve the quality of care for these patients., Purpose: This study aims to assess the management and outcomes in this population group compared with patients with true carotid occlusion., Data Sources: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a comprehensive systematic review was conducted by using PubMed, Embase, Web of Science, and Scopus from database inception to November 2023., Study Selection: The size of the included studies ranged from 16 patients to 146 patients. Through the 4 full-text articles, a total of 259 patients were collected. We compared outcomes between patients with cICA-PO compared with patients with true carotid occlusions undergoing EVT due to AIS. We excluded studies with patients with carotid pseudo-occlusion without stroke, review articles, duplicate studies, overlapped data that included the same patients presented in another included study, case reports, case series with fewer than 5 patients, and meeting abstracts that did not contain the outcomes of interest. We did not pose any limitations regarding sample size or patient characteristics., Data Analysis: We utilized the R statistical software (V.4.3.1; R package meta) to conduct the analysis of all the data obtained. We calculated the OR for binary variables, and the corresponding 95% CI. To synthesize the data, random-effect models, as well as forest plots were generated to visually represent the synthesis of the data. Additionally, we assessed heterogeneity by using Cochran Q and I 2 tests. A P value < .05 for the Q statistic or I 2 more than 50% suggests notable heterogeneity. Based on a small number of studies (<10), the assessment of publication bias could not be reliably performed., Data Synthesis: This meta-analysis encompassed data from 4 studies. Patients with cICA-PO and AIS who underwent EVT ( n = 135) exhibited lower rates of functional independence (OR = 0.35; 95% CI, 0.20-0.61; P < .001) compared with patients with true occlusions ( n = 103), as well as successful recanalization rates (OR = 0.39; 95% CI, 0.20-0.74; P  = .004). In addition, the cICA-PO group experienced higher mortality and symptomatic intracranial hemorrhage (sICH) compared with the group with true carotid occlusions (OR = 2.62; 95% CI, 0.21-7.24; and OR = 2.23; 95% CI, 1.00-4.95; P = .049, respectively)., Limitations: Individual patient data were not available. Studies were a retrospective design and some of the studies had small sample sizes. The included studies in our meta-analysis did not exclude patients with tandem occlusions that might influence the results of the comparison., Conclusions: Compared with patients with true carotid occlusion, the cICA-PO group with AIS undergoing EVT presented poor outcomes with lower functional independence and successful recanalization, as well as higher sICH and mortality rates., (© 2024 by American Journal of Neuroradiology.)

Background: When treating acute ischemic stroke due to large-vessel occlusion, both mechanical thrombectomy and intravenous (IV) thrombolysis carry the risk of intracerebral hemorrhage., Purpose: This study aimed to delve deeper into the risk of intracerebral hemorrhage and its subtypes associated with mechanical thrombectomy with or without IV thrombolysis to contribute to better decision-making in the treatment of acute ischemic stroke due to large-vessel occlusion., Data Sources: PubMed, EMBASE, and Scopus databases were searched for relevant studies from inception to September 6, 2023., Study Selection: The eligibility criteria included randomized clinical trials or post hoc analysis of randomized controlled trials that focused on patients with acute ischemic stroke in the anterior circulation. After screening 4870 retrieved records, we included 9 studies (6 randomized controlled trials and 3 post hoc analyses of randomized controlled trials) with 3241 patients., Data Analysis: The interventions compared were mechanical thrombectomy + IV thrombolysis versus mechanical thrombectomy alone, with the outcome of interest being any form of intracerebral hemorrhage and symptomatic intracerebral hemorrhage after intervention. A common definition for symptomatic intracerebral hemorrhage was pooled from various classification systems, and subgroup analyses were performed on the basis of different definitions and anatomic descriptions of hemorrhage. The quality of the studies was assessed using the revised version of Cochrane Risk of Bias 2 assessment tool. Meta-analysis was performed using the random effects model., Data Synthesis: Eight studies had some concerns, and 1 study was considered high risk. Overall, the risk of symptomatic intracerebral hemorrhage was comparable between mechanical thrombectomy + IV thrombolysis and mechanical thrombectomy alone (risk ratio, 1.24 [95% CI, 0.89-1.72]; P = .20), with no heterogeneity across studies. Subgroup analysis of symptomatic intracerebral hemorrhage showed a non-significant difference between 2 groups based on the National Institute of Neurological Disorders and Stroke ( P = .3), the Heidelberg Bleeding Classification ( P = .5), the Safe Implementation of Thrombolysis in Stroke-Monitoring Study ( P = .4), and the European Cooperative Acute Stroke Study III ( P = .7) criteria. Subgroup analysis of different anatomic descriptions of intracerebral hemorrhage showed no difference between the 2 groups. Also, we found no difference in the risk of any intracerebral hemorrhage between two groups (risk ratio, 1.10 [95% CI, 1.00-1.21]; P = .052) with no heterogeneity across studies., Limitations: There was a potential for performance bias in most studies., Conclusions: In this systematic review and meta-analysis, the risk of any intracerebral hemorrhage and symptomatic intracerebral hemorrhage, including its various classifications and anatomic descriptions, was comparable between mechanical thrombectomy + IV thrombolysis and mechanical thrombectomy alone., (© 2024 by American Journal of Neuroradiology.)

Background The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion. Purpose To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion. Materials and Methods This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and multivariable logistic regression analyses were performed to test the association between the addition of IVT treatment and different functional and safety outcomes. Results After propensity score matching, 670 patients (median age, 75 years [IQR, 64-82 years]; 356 female) were included in the analysis; 335 underwent MT alone and 335 underwent MT with IVT. Median onset to puncture (350 vs 210 minutes, P < .001) and onset to recanalization (397 vs 273 minutes, P < .001) times were higher in the MT group than the MT with IVT group, respectively. In the univariable regression analysis, the addition of IVT was associated with higher odds of a modified Rankin Scale (mRS) score 0-2 (odds ratio [OR], 1.44; 95% CI: 1.06, 1.96; P = .019); however, this association was not observed in the multivariable analysis (OR, 1.37; 95% CI: 0.99, 1.89; P = .054). In the multivariable analysis, the addition of IVT also showed no evidence of an association with the odds of first-pass effect (OR, 1.27; 95% CI: 0.9, 1.79; P = .17), Thrombolysis in Cerebral Infarction grades 2b-3 (OR, 1.64; 95% CI: 0.99, 2.73; P = .055), mRS scores 0-1 (OR, 1.27; 95% CI: 0.91, 1.76; P = .16), mortality (OR, 0.78; 95% CI: 0.49, 1.24; P = .29), or intracranial hemorrhage (OR, 1.25; 95% CI: 0.88, 1.76; P = .21). Conclusion Adjunctive IVT may not provide benefit to MT in patients with AIS caused by distal and medium vessel occlusion. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wojak in this issue.

Objective: To assess the role of net water uptake (NWU) in predicting outcomes in acute ischemic stroke (AIS) patients., Methods: A systematic review and meta-analysis were performed, adhering to established guidelines. The search covered PubMed, Scopus, Web of Science, and Embase databases until July 1, 2023. Eligible studies reporting quantitative ischemic lesion NWU in admission CT scans of AIS patients, stratified based on outcomes, were included. Data analysis was performed using R software version 4.2.1., Results: Incorporating 17 original studies with 2217 AIS patients, NWU was significantly higher in patients with poor outcomes compared to those with good outcomes (difference of medians: 5.06, 95% CI: 3.00-7.13, p < 0.001). Despite excluding one outlier study, considerable heterogeneity persisted among the included studies (I 2  = 90.8%). The meta-regression and subgroup meta-analyses demonstrated significantly higher NWU in patients with poor functional outcome, as assessed by modified Rankin Scale (difference of medians: 3.83, 95% CI: 1.98-5.68, p < 0.001, I 2  = 72.9%), malignant edema/infarct (difference of medians: 8.30, 95% CI: 4.01-12.58, p < 0.001, I 2  = 95.6%), and intracranial hemorrhage (difference of medians: 5.43, 95% CI: 0.44-10.43, p = 0.03, I 2  = 91.1%)., Conclusion: NWU on admission CT scans shows promise as a predictive marker for outcomes in AIS patients. Prospective, multicenter trials with standardized, automated NWU measurement are crucial for robustly predicting diverse clinical outcomes., Clinical Relevance Statement: The potential of net water uptake as a biomarker for predicting outcomes in acute ischemic stroke patients holds significant promise. Further validation through additional research could lead to its integration into clinical practice, potentially improving the accuracy of clinical decision-making and allowing for the development of more precise patient care strategies., Key Points: • Net water uptake, a CT-based biomarker, quantifies early brain edema after acute ischemic stroke. • Net water uptake is significantly higher in poor outcome acute ischemic stroke patients. • Net water uptake on CT scans holds promise in predicting diverse acute ischemic stroke outcomes., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: Acute ischemic stroke (AIS) imposes a major healthcare burden, with the elderly population often underrepresented in clinical trials. This systematic review and network meta-analysis aims to evaluate the safety and efficacy of mechanical thrombectomy (MT) among octogenarians and nonagenarians with AIS due to large vessel occlusion (LVO)., Methods: A systematic search was conducted using PubMed, Web of Science, and Scopus databases. Outcomes of interest were modified Rankin Scale (mRS) score of 0-2, thrombolysis in cerebral infarction (TICI) score of 2b-3, 90-day mortality, and symptomatic intracerebral hemorrhage (sICH). The study followed Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines., Results: The analysis included 47 studies. Significantly lower rates of mRS score 0-2 were observed in nonagenarians (17.4 %) and octogenarians (21.3 %) compared to younger (40.2 %) patients (Odds Ratio (OR) = 3.30, 95 % Confidence Interval (CI):2.35-4.65 and OR = 2.47, 95 % CI: 2.07-2.94). 90-day mortality was significantly higher in nonagenarians (38.9 %) compared to octogenarians (25.4 %) and younger (14.0 %) patients (OR = 0.58, 95 % CI: 0.41-0.83 and OR = 0.31, 95 % CI: 0.21-0.44), and in octogenarians compared to younger patients (OR = 0.52, 95 % CI: 0.41-0.66). No significant differences were observed in TICI 2b-3 and sICH rates across groups., Conclusions: Our findings indicate that MT is a viable treatment option for AIS due to LVO among octogenarians and nonagenarians, albeit with nuanced differences. Specifically, octogenarians had lower 90-day mortality rates compared to nonagenarians. These insights support the need for individualized treatment plans for elderly patients with AIS due to LVO and highlight the importance of including this demographic in future clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Stroke is a leading cause of mortality and disability globally, with limited treatment options available for acute ischemic stroke (AIS) patients. Type 2 diabetes mellitus (T2DM) is not only widespread but also a known risk factor for stroke. Our meta-analysis aims to assess the influence of pre-stroke metformin use on the clinical outcomes in AIS patients with T2DM., Materials and Methods: We conducted this study following PRISMA guidelines, searching the following databases: Medline, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials up to February 29, 2024. All studies providing separate data on AIS patients using metformin were included, and statistical analysis was conducted using R software to pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI)., Results: Out of 1051 studies, 7 met the inclusion criteria for our meta-analysis with a total of 11589 diabetic patients, including 5445 patients taking metformin and 6144 diabetic patients in the non-metformin group. Compared to the non-metformin group, the metformin group had a significantly higher rate of mRS 0-2 score at discharge (OR 1.56; 95% CI 1.25:1.95; p=< 0.01) and a lower rate of 90-day mortality (OR 0.51; 95% CI 0.42:0.61; p=< 0.01), with no significant difference in sICH (OR 0.88; 95% CI 0.47:1.64; p= 0.68) between the two groups., Conclusions: Our meta-analysis demonstrated that pre-stroke metformin use is associated with higher functional independence and lower mortality in AIS patients with T2DM., Competing Interests: Declaration of competing interest Dr. Ramanathan Kadirvel: Grant support from Medtronic, Frontior Bio, Ancure LLC, MIVI Biosciences, Stryker Inc, Conway Medical, Piraeus Medical, Bionau Labs Dr. Waleed Brinjikji: Equity in Nested Knowledge, Superior Medical Editors, Piraeus Medical, Sonoris Medical, and MIVI Neurovascular. He receives royalties from Medtronic and Balloon Guide Catheter Technology. He receives consulting fees from Medtronic, Stryker, Imperative Care, Microvention, MIVI Neurovascular, Cerenovus, Asahi, and Balt. He serves in a leadership or fiduciary role for MIVI Neurovascular, Marblehead Medical LLC, Interventional Neuroradiology (Editor in Chief), Piraeus Medical, and WFITN. Dr. Alejandro A Rabinstein: CEC committee member for trials sponsored by Boston Scientific and has participated in advisory board meetings for Astra Zeneca, Novo Nordisk, Shionogi, and Brainomix. Dr. David F Kallmes: Equity in Nested Knowledge, Superior Medical Editors, and Conway Medical, Marblehead Medical and Piraeus Medical. He receives grant support from MicroVention, Medtronic, Balt, and Insera Therapeutics; has served on the Data Safety Monitoring Board for Vesalio; and received royalties from Medtronic., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Mechanical thrombectomy (MT) has revolutionized the treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO), but its efficacy and safety in medium vessel occlusion (MeVO) remain less explored. This multicenter, retrospective study aims to investigate the incidence and clinical outcomes of vessel perforations (confirmed by extravasation during an angiographic series) during MT for AIS caused by MeVO., Methods: Data were collected from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. A total of 1373 AIS patients with MeVO underwent MT. Baseline characteristics, procedural details, and clinical outcomes were analyzed., Results: The incidence of vessel perforation was 4.8% (66/1373). Notably, our analysis indicates variations in perforation rates across different arterial segments: 8.9% in M3 segments, 4.3% in M2 segments, and 8.3% in A2 segments ( p  = 0.612). Patients with perforation had significantly worse outcomes, with lower rates of favorable angiographic outcomes (TICI 2c-3: 23% vs 58.9%, p  < 0.001; TICI 2b-3: 56.5% vs 88.3%, p  < 0.001). Functional outcomes were also worse in the perforation group (mRS 0-1 at 3 months: 22.7% vs 36.6%, p  = 0.031; mRS 0-2 at 3 months: 28.8% vs 53.9%, p  < 0.001). Mortality was higher in the perforation group (30.3% vs 16.8%, p  = 0.008)., Conclusion: This study reveals that while the occurrence of vessel perforation in MT for AIS due to MeVO is relatively rare, it is associated with poor functional outcomes and higher mortality. The findings highlight the need for increased caution and specialized training in performing MT for MeVO. Further prospective research is required for risk mitigation strategies., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. Prof. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading), and Artedrone (Board); all not directly related to the present work. Dr. Henninger received support from NINDS NS131756, during the conduct of the study. Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. Dr. Nguyen reports advisory board with Idorsia. Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro, and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson, and Phenox (paid lectures), all not directly related to the present work. Pr Sibon reports conflict of interest with Medtronic, Sanofi, Bayer, Boehringer-Ingelheim, Novartis, Novo-Nordisk, BMS-Pfizer (board and paid lectures), all not directly related to the present work. Dr. Yedavalli is a consultant for RAPID (Ischemaview, Menlo Park, CA). Dr. Vagal is a consultant for Viz AI. She is also PI of Imaging core lab for ENDOLOW study funded by Cerenovus (monies go to the institution). Dr. Gopinathan reports conflicts of interest with Microvention, Stryker Neurovascular, Medtronic, BD, Penumbra (paid lectures, workshops, and proctoring), all not directly related to the present work. Dr. Bernstock has an equity position in Treovir Inc., an oHSV clinical stage company and UpFront Diagnostics. JDB is also on the Centile Bioscience and NeuroX1 boards of scientific advisors.

Background: Recent studies indicate endovascular thrombectomy (EVT) as a safe, effective treatment for acute ischemic stroke (AIS) with large ischemic regions. Our study updates an ongoing living systematic review and meta-analysis of randomized controlled trials (RCTs) comparing outcomes of EVT to medical management only., Methods: We searched MEDLINE, EMBASE, and the Cochrane Library for RCTs comparing EVT to medical management in AIS patients with large ischemic areas. Using fixed-effect models, we conducted a meta-analysis to compare functional independence, mortality, and symptomatic intracranial hemorrhage (sICH) between EVT and standard medical management. We evaluated bias risk with the Cochrane tool and graded the certainty of evidence using the GRADE approach., Results: Of 1363 new citations, we included six RCTs with a total of 1876 patients. We found low-certainty evidence of improved functional independence (risk difference [RD] 29.9%, 95% CI 17.2% to 46.9%), increase in sICH (RD 2.6%, 95% CI 0.3% to 6.4%), and a non-significant decrease in mortality (RD -1.8%, 95% CI -3.9% to 0.6%) for AIS patients with large infarcts who underwent EVT compared to medical management only., Conclusion: Our revised meta-analysis suggests low-certainty evidence that there is improved functional independence, a non-significant decrease in mortality, and an increase in sICH among AIS patients with large infarcts who undergo EVT compared to those receiving medical management alone., Systematic Review Protocol Registration: PROSPERO (CRD42023398742)., Competing Interests: Declaration of competing interest All authors reported no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Endovascular therapy (EVT) has been proven beneficial for treating acute ischemic strokes (AIS) with large vessel occlusion (LVO). Recent trials of DAWN and DEFUSE-3 have extended the treatment window to 6-24 h, sparking investigations into EVT outcomes for patients not eligible for DAWN/DEFUSE-3 criteria., Purpose: To assess the outcomes of endovascular therapy (EVT) for late-window anterior circulation large vessel occlusion (LVO) in acute ischemic stroke patients, comparing DAWN/DEFUSE-3 eligible (DD) and ineligible (NDND) groups., Methods: This systematic review and meta-analysis examined EVT outcomes for patients with late-window anterior circulation LVO beyond 6 h. We categorized patients as DAWN/DEFUSE-3 eligible (DD) and ineligible (NDND). Our search covered PubMed, Embase, Web of Science, and Scopus. A total of 464 records were initially identified. After duplicate removal, 298 studies were screened. Nine studies were included and analyzed. Our analysis focused on study characteristics, baseline comparisons, risk of bias, and outcomes., Results: Baseline characteristics showed comparable age, gender, most comorbidities, NIHSS score, and ASPECTS between DAWN/DEFUSE-3 eligible (DD) and ineligible (NDND) patients. NDND patients' history showed a higher rate of atrial fibrillation and larger infarct volumes on baseline imaging. Successful reperfusion rates (TICI 2b-3) were similar between DD and NDND with 354 out of 469 in the DD group and 364 out of 459 in the NDND group (OR = 0.86; 95% CI 0.40, 1.84; p = 0.689), though with significant heterogeneity (I 2  = 73%; P = 0.002). The proportion of patients with distal occlusions was significantly higher in the NDND group as compared to the DD group (137 (39.4%) of 347 patients versus 47 (11%) of 428 patients, respectively), with significant heterogeneity across studies (I 2  = 85%, p = 0.023). Functional independence at 90 days (mRS 0-2) showed no significant difference between groups with 259 out of 802 in the DD group and 197 out of 668 in the NDND group (OR = 1.12; 95% CI 0.77, 1.63; p = 0.552) but also exhibited notable heterogeneity (I 2  = 46%, p = 0.063). Symptomatic intracranial hemorrhage (sICH) rates were lower in DD with 14 out of 309 in the DD group and 47 out of 400 in NDND group (OR = 0.49; 95% CI 0.25, 0.93; p = 0.029) as compared to the NDND patients, showing no heterogeneity (I 2  = 0%, p = 0.552). 90-day mortality was lower in DD with 43 out of 304 in the DD group and 107 out of 399 in the NDND group (OR = 0.55; 95% CI 0.37, 0.82; p = 0.004) as compared to NDND patients, with no significant heterogeneity (I 2  = 0%, p = 0.536)., Conclusion: This meta-analysis demonstrates equivalent rates of functional independence between DD and NDND patients. However, the high proportion of distal occlusions and higher rates of sICH and mortality in NDND patients suggest caution in offering mechanical thrombectomy to DAWN/DEFUSE-3 ineligible patients. A more flexible approach to EVT eligibility criteria could benefit select patients in real-world practice. Nonetheless, further research is needed to identify which patients would benefit from expanded EVT eligibility criteria., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: Our purpose was to assess the efficacy and safety of the pRESET LITE stent retriever (Phenox, Bochum, Germany), designed for medium vessel occlusion (MeVO) in acute ischemic stroke (AIS) patients with a primary MeVO., Methods: We performed a retrospective analysis of the MAD MT Consortium, an integration of prospectively maintained databases at 37 academic institutions in Europe, North America, and Asia, of AIS patients who underwent mechanical thrombectomy with the pRESET LITE stent retriever for a primary MeVO. We subcategorized occlusions into proximal MeVOs (segments A1, M2, and P1) vs. distal MeVOs/DMVO (segments A2, M3-M4, and P2). We reviewed patient and procedural characteristics, as well as angiographic and clinical outcomes., Results: Between September 2016 and December 2021, 227 patients were included (50% female, median age 78 [65-84] years), of whom 161 (71%) suffered proximal MeVO and 66 (29%) distal MeVO. Using a combined approach in 96% of cases, successful reperfusion of the target vessel (mTICI 2b/2c/3) was attained in 85% of proximal MeVO and 97% of DMVO, with a median of 2 passes (IQR: 1-3) overall. Periprocedural complications rate was 7%. Control CT at day 1 post-MT revealed a hemorrhagic transformation in 63 (39%) patients with proximal MeVO and 24 (36%) patients with DMVO, with ECASS-PH type hemorrhagic transformations occurring in 3 (1%) patients. After 3 months, 58% of all MeVO and 63% of DMVO patients demonstrated a favorable outcome (mRS 0-2)., Conclusion: Mechanical thrombectomy using the pRESET LITE in a combined approach with an aspiration catheter appears effective for primary medium vessel occlusions across several centers and physicians., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The risk of acute ischemic stroke (AIS) associated with high estrogen states, including pregnant patients and those using oral contraceptives, has been well documented. We described the histological composition of thrombi collected in these cases., Methods: From a prospective tissue registry (STRIP registry) of thrombi retrieved during mechanical thrombectomy for AIS, we identified 5 patients with high estrogen states: 1 post-partum patient, 1 undergoing hormone replacement therapy and 3 consuming oral contraceptive pills. Five male control patients were randomly chosen matched by age. Immunohistochemistry for CD42b (platelets), von Willebrand factor (vWF), thrombin-activatable fibrinolysis inhibitor (TAFI), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) was performed. Expression was quantified using Orbit Image Software. Student's t-test was performed as appropriate., Results: Mean TAFI content for the high estrogen state group was higher than controls (25.6 ± 11.9% versus 9.3 ± 9.0%, p = 0.043*). Mean platelet content for the high estrogen state group was lower than controls (41.7 ± 10.6% versus 61.8 ± 12.9%, p = 0.029*). No significant difference was found in vWF, fibrinogen and PAI-1 expression. Mean time to recanalize was higher in the high estrogen state group compared to the control group (57.8 ± 27.6 versus 22.6 ± 11.4 min, p = 0.0351*). The mean number of passes required was higher in the high estrogen group compared to controls 4.6 versus 1.2, p = 0.0261*)., Conclusions: TAFI expression, a powerful driver of thrombosis, was significantly higher in stroke thrombi among patients with high estrogen states compared to controls., (© 2024. The Author(s).)

Objective: Radiomics is a machine-learning method that extracts features from medical images. The objective of the present systematic review was to assess the quality of existing studies that use radiomics methods to predict functional outcomes in patients after acute ischemic stroke., Methods: Studies using radiomics-extracted features to predict functional outcomes among patients with acute ischemic stroke using the modified Rankin Scale were included. PubMed, Scopus, Web of Science, and Embase were screened using the terms "radiomics" and "texture" in combination with "stroke." Quality scores were calculated based on Radiomics Quality Score, the IBSI (Image Biomarkers Standardization Initiative), and the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2)., Results: Fourteen studies were included. The median total Radiomics Quality Score was 14.5 (13-16) out of 36. Domains 1, 5, and 6 on protocol quality and stability of imaging and segmentation, level of evidence, and use of open science and data, respectively, were poor. Median IBSI score was 2.5 (1-5) out of 6. Few studies included bias-field correction algorithms, isovoxel resampling, skull stripping, or gray-level discretization. Of 14 studies, none received +6 points, 1 received +5 points, 5 received +4 points, 1 study received +3 points, 5 received +2 points, 2 received +1 points, and none received 0 points. As per the QUADAS-2, 6/14 (42.9%) studies had a risk of bias concern and 0/14 (0%) had applicability concern., Conclusions: The quality of the included studies was low to moderate. With increasing use of radiomics, future studies should attempt to adhere to and report established radiomics quality guidelines., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Endovascular thrombectomy (EVT) is standard treatment for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO), but optimal post-EVT blood pressure (BP) control remains debated., Objective: To assess the association of different systolic BP targets following EVT with functional outcomes, mortality, and complications in patients with AIS due to LVO., Data Sources: Systematic review and meta-analysis of databases (PubMed, Embase, Web of Science, Scopus, and Cochrane Library) to September 8, 2023., Study Selection: Inclusion criteria consisted of randomized clinical trials examining post-EVT management of systolic BP in patients with AIS and LVO comparing intensive vs conventional targets. Nonrandomized studies, observational studies, noninterventional trials, meeting abstracts, duplicate studies, studies with overlapping data, and non-English language studies were excluded. Two authors independently applied these criteria through a blinded review, with discrepancies resolved through consensus. The risk of bias in the included studies was assessed using the revised tool for assessing risk of bias in randomized trials., Data Extraction and Synthesis: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Three authors extracted data regarding study characteristics, baseline patient data, and outcomes of interest. The pooled data were analyzed using a random-effects meta-analysis., Main Outcomes and Measures: Rates of functional independence, 90-day mortality, symptomatic intracranial hemorrhage, and hypotensive events., Results: A total of 4 randomized clinical trials with 1571 initially enrolled patients were included in the analysis. Lower functional independence rates were observed in the intensive control group (relative risk [RR], 0.81 [95% CI, 0.67-0.98]). No significant differences were found in 90-day mortality (RR, 1.18 [95% CI, 0.92-1.52]), symptomatic intracranial hemorrhage (RR, 1.12 [95% CI, 0.75-1.67]), or hypotensive events (RR, 1.80 [95% CI, 0.37-8.76]). There was minimal heterogeneity among the studies included in the functional independence outcome (I2 = 13% and τ2 = 0.003), which was absent among other outcomes (I2 = 0 and τ2 = 0)., Conclusions and Relevance: These findings suggest that intensive post-EVT BP reduction does not yield benefits and may carry risks. While awaiting the results of additional ongoing trials, a conservative BP management strategy after endovascular recanalization is favored in daily practice.

Background: Federal research funding is highly sought after but may be challenging to attain. A clear understanding of funding for specific diseases, such as cerebrovascular disorders, might help researchers regarding which National Institutes of Health (NIH) institutes fund research into specific disorders and grant types., Objective: To examine the current scope of NIH grant funding for cerebrovascular conditions., Methods: The NIH-developed RePORTER was used to extract active NIH-funded studies related to cerebrovascular diseases through January 2023. Duplicate studies were removed, and projects were manually screened and labeled in subcategories as clinical and basic science and as research subcategories. Extracted data included total funding, grant types, institutions that received funding, and diseases studied. Python (version 3.9) and SciPy library were used for statistical analyses., Results: We identified 1232 cerebrovascular projects across seven diseases with US$699 952 926 in total funding. The cerebrovascular diseases with the greatest number of grants were ischemic stroke (705, or 57.2% of all funded projects), carotid disease (193, or 15.7%), and hemorrhagic stroke (163, or 13.2%). R01 grants were the most common mechanism of funding (632 grants, or 51.3%). The National Institute of Neurological Disorders and Stroke (NINDS) funded the most projects (504 projects; US$325 536 405), followed by the National Heart, Lung, and Blood Institute (NHLBI) (376 projects; US$216 784 546)., Conclusion: Cerebrovascular disease receives roughly US$700 million in NIH funding. Ischemic stroke accounts for the majority of NIH-funded cerebrovascular projects, and R01 grants are the most common funding mechanism. Notably, NHLBI provides a large proportion of funding, in addition to NINDS., Competing Interests: Competing interests: DFK holds equity in Nested Knowledge, Superior Medical Editors, and Conway Medical, Marblehead Medical, and Piraeus Medical; he receives grant support from MicroVention, Medtronic, Balt, and Insera Therapeutics; has served on the Data Safety Monitoring Board for Vesalio; and received royalties from Medtronic. WB holds equity in Nested Knowledge, Superior Medical Editors, Piraeus Medical, Sonoris Medical, and MIVI Neurovascular; he receives royalties from Medtronic and Balloon Guide Catheter Technology; he receives consulting fees from Medtronic, Stryker, Imperative Care, Microvention, MIVI Neurovascular, Cerenovus, Asahi, and Balt; he serves in a leadership or fiduciary role for MIVI Neurovascular, Marblehead Medical LLC, Interventional Neuroradiology (editor in chief), Piraeus Medical, and WFITN., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Predicting patient recovery and discharge disposition following mechanical thrombectomy remains a challenge in patients with ischemic stroke. Machine learning offers a promising prognostication approach assisting in personalized post-thrombectomy care plans and resource allocation. As a large national database, National Inpatient Sample (NIS), contain valuable insights amenable to data-mining. The study aimed to develop and evaluate ML models predicting hospital discharge disposition with a focus on demographic, socioeconomic and hospital characteristics., Materials and Methods: The NIS dataset (2006-2019) was used, including 4956 patients diagnosed with ischemic stroke who underwent thrombectomy. Demographics, hospital characteristics, and Elixhauser comorbidity indices were recorded. Feature extraction, processing, and selection were performed using Python, with Maximum Relevance - Minimum Redundancy (MRMR) applied for dimensionality reduction. ML models were developed and benchmarked prior to interpretation of the best model using Shapley Additive exPlanations (SHAP)., Results: The multilayer perceptron model outperformed others and achieved an AUROC of 0.81, accuracy of 77 %, F1-score of 0.48, precision of 0.64, and recall of 0.54. SHAP analysis identified the most important features for predicting discharge disposition as dysphagia and dysarthria, NIHSS, age, primary payer (Medicare), cerebral edema, fluid and electrolyte disorders, complicated hypertension, primary payer (private insurance), intracranial hemorrhage, and thrombectomy alone., Conclusion: Machine learning modeling of NIS database shows potential in predicting hospital discharge disposition for inpatients with acute ischemic stroke following mechanical thrombectomy in the NIS database. Insights gained from SHAP interpretation can inform targeted interventions and care plans, ultimately enhancing patient outcomes and resource allocation., Competing Interests: Declaration of Competing Interest D.F.K. holds equity in Nested Knowledge, Superior Medical Editors, and Conway Medical, Marblehead Medical and Piraeus Medical. He receives grant support from MicroVention, Medtronic, Balt, and Insera Therapeutics; has served on the Data Safety Monitoring Board for Vesalio; and received royalties from Medtronic. A.A.R. serves in the CEC committee for trials sponsored by Boston Scientific and has participated in advisory board meetings for Astra Zeneca and Novo Nordisk. WB holds equity in Nested Knowledge, Superior Medical Editors, Piraeus Medical, Sonoris Medical, and MIVI Neurovascular; he receives royalties from Medtronic and Balloon Guide Catheter Technology; he receives consulting fees from Medtronic, Stryker, Imperative Care, Microvention, MIVI Neurovascular, Cerenovus, Asahi, and Balt; he serves in a leadership or fiduciary role for MIVI Neurovascular, Marblehead Medical LLC, Interventional Neuroradiology (editor in chief), Piraeus Medical, and WFITN., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Current guidelines recommend best medical treatment (BMT) over revascularization for carotid near-occlusion (CNO); however, it remains unclear whether BMT, carotid artery stenting (CAS), or carotid endarterectomy (CEA) is the optimal treatment strategy. The present meta-analysis aimed to compare outcomes among patients with CNO receiving BMT, CAS, or CEA., Methods: PubMed, Web of Science, Scopus, and Embase were searched. English studies with ≥1 month follow-up, that used established CNO diagnostic guidelines, that provided outcomes by treatment, and in which 95% confidence intervals (CIs) were calculable were included. Studies on acute ischemic stroke (AIS) requiring emergent reperfusion therapy, nonatherosclerotic lesions, nonprimary research articles, non-English, and nonhuman studies were excluded. Outcomes were mortality, AIS, transient ischemic attack, myocardial infarction within and beyond 30 days, and restenosis. A generalized linear mixed model, subgroup analysis, and meta-regression were used to compare outcomes., Results: Thirty-eight studies were included. Pooled rates for AIS beyond 30 days were 9.90% (95% CI, 4.31%-21.16%), 0.79% (95% CI, 0.24%-2.53%), and 0.80% (95% CI, 0.15%-4.07%) for BMT, CAS, and CEA, respectively. Subgroup analysis was statistically significant (P < 0.001). Meta-regression showed lower incidence favoring procedural intervention (CAS vs. BMT, P = 0.001; CEA vs. BMT, P = 0.003). Subgroup analysis for mortality beyond 30 days was also significant (P = 0.016) but meta-regression did not favor one treatment over another. Other outcomes were not statistically significant., Conclusions: Revascularization for CNO may decrease long-term stroke rates. Given that current guidelines are based on randomized controlled trials from the 1990s, updated randomized trials are warranted to determine the optimal treatment for CNO., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Previous randomized controlled trials (RCTs) and meta-analyses were underpowered to demonstrate the superiority of endovascular thrombectomy (EVT) over medical therapy (MEDT) in the treatment of acute ischemic stroke due to large vessel occlusion of the posterior circulation (PC-LVO). We performed an updated systematic review and meta-analysis after the publication of the BAOCHE and ATTENTION trials to determine whether EVT can benefit patients presenting with PC-LVO., Methods: Using Nested Knowledge, we screened literature for RCTs on EVT in PC-LVO. The primary outcome was 90-day modified Rankin Scale (mRS) score 0-3, and secondary outcomes included 90-day mRS score 0-2, 90-day mortality, and rate of symptomatic intracranial hemorrhage (sICH). A random-effects model was used to compute rate ratios (RRs) and their corresponding 95% confidence intervals (CIs)., Results: Four RCTs with 988 patients, 556 patients in the EVT arm and 432 patients in the MEDT arm, were included in the meta-analysis. EVT resulted in significantly higher rates of mRS score 0-3 (RR=1.54; 95% CI 1.16 to 2.04; P=0.002) and functional independence (RR=1.83; 95% CI 1.08 to 3.08; P=0.024), and lower rates of mortality (RR=0.76; 95% CI 0.65 to 0.90; P=0.002) at 90-day follow-up compared with MEDT alone. However, EVT patients had higher rates of sICH (RR=7.48; 95% CI 2.27 to 24.61; P<0.001)., Conclusions: EVT conferred significant patient benefit over MEDT alone in the treatment of PC-LVO. Future studies should better define patients for whom EVT is futile and determine factors that contribute to higher rates of sICH., Competing Interests: Competing interests: JJH is a consultant for Medtronic and MicroVention, a member of the medical and scientific advisory board for iSchemaView, and a member of the JNIS Editorial Board as a Member-at-Large in Neuroradiology. GWA is a consultant for Genentech and iSchemaView and holds equity in iSchemaView. DFK holds equity in Nested Knowledge, Superior Medical Editors, and Conway Medical, Marblehead Medical and Piraeus Medical; receives grant support from MicroVention, Medtronic, Balt, and Insera Therapeutics; has served on the Data Safety Monitoring Board for Vesalio; and received royalties from Medtronic. WB has compensation for consultant services from Johnson & Johnson, Stryker, Medtronic Vascular and Microvention; compensation from MIVI Neurovascular for data and safety monitoring services; stock holdings from Marblehead Medical LLC. KH works for Nested Knowledge, Inc. KMK works for, and holds equity in, Nested Knowledge, Inc., works for Conway Medical LLC, and holds equity in Superior Medical Experts, Inc. NH works for and holds equity in Nested Knowledge, Inc., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Metabolites are reliable biomarkers for many diseases. However, their role in acute ischemic stroke (AIS) pathogenesis is not well understood. In this systematic review we aim to evaluate the current literature on the presence of metabolites in thrombi retrieved by mechanical thrombectomy from AIS patients. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines, we searched OVID Medline, PubMed, OVID Embase, Scopus, and Web of Science until July 13, 2022. Metabolites lists were extracted, and pathway analysis was performed in MetaboAnalyst database. Four articles listing metabolites were included in this systematic review. D-Glucose, diacylglycerol, phytosphingosine, galabiosylceramide, glucosylceramide and 4-hydroxynonenal were reported to be associated with clots. Metabolomics data analysis showed that glycolysis, lactose, and sphingolipid metabolism pathways were enriched. In conclusion, results of the present study show that the thrombi niche has a glycolytic phenotype. Future studies should work to better understand the metabolic properties of AIS thrombi., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: First-pass effect (FPE) has been shown to be a predictor of favorable clinical outcomes following endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) in the anterior circulation. Literature regarding FPE for posterior circulation AIS is sparse; we conducted a systematic review and meta-analysis to explore FPE in posterior circulation stroke undergoing EVT., Materials and Methods: We conducted a systematic review of the English literature in PubMed, Embase, Scopus, and Web of Science. FPE was defined as thrombolysis in cerebral infarction (TICI) 2c-3 and modified FPE (mFPE) was defined as TICI 2b-3 in one pass. Definitions of non-FPE and non-mFPE varied among studies. The primary outcome of interest was modified Rankin Scale (mRS) 0-2. Secondary outcomes of interest were mRS 0-3, symptomatic intracranial hemorrhage (sICH), and mortality. We calculated odds ratios (OR) and corresponding 95% confidence intervals (CI). Heterogeneity was assessed with Q statistic and I 2 test., Results: Seven studies with 417 patients in the mFPE group, 942 in the non-mFPE group, 545 in the FPE group, and 1023 in the non-FPE group were included. Overall, FPE was associated with greater rates of 90-day mRS 0-2 (OR= 2.78, 95% CI= 2.11-3.65; P-value< 0.001) and mRS 0-3 (OR= 2.67, 95% CI= 1.98-3.60; P-value< 0.001); however, there was significant heterogeneity among studies for both mRS 0-2 (I 2 = 69%; P-value< 0.001) and mRS 0-3 (I 2 = 69%; P-value< 0.001). FPE and non-FPE were associated with similar rates of sICH (OR= 0.65, 95% CI= 0.40-1.07; P-value= 0.09), and no heterogeneity was observed (I 2 = 0%; P-value= 0.95). FPE was associated with lower rates of mortality (OR= 0.44, 95% CI= 0.33-0.58; P-value< 0.001), although heterogeneity was observed (I 2 = 58%; P-value= 0.01)., Conclusions: FPE is associated with favorable clinical outcomes in patients undergoing EVT for posterior circulation AIS. Future studies should work to further quantify the impact of FPE on outcomes in the posterior circulation., Competing Interests: Declaration of Competing Interest D.F.K. holds equity in Nested Knowledge, Superior Medical Editors, and Conway Medical, Marblehead Medical and Piraeus Medical. He receives grant support from MicroVention, Medtronic, Balt, and Insera Therapeutics; has served on the Data Safety Monitoring Board for Vesalio; and received royalties from Medtronic. W.B. holds equity in Nested Knowledge, Superior Medical Editors, Piraeus Medical, Sonoris Medical, and MIVI Neurovascular. He receives royalties from Medtronic and Balloon Guide Catheter Technology. He receives consulting fees from Medtronic, Stryker, Imperative Care, Microvention, MIVI Neurovascular, Cerenovus, Asahi, and Balt. He serves in a leadership or fiduciary role for MIVI Neurovascular, Marblehead Medical LLC, Interventional Neuroradiology (Editor in Chief), Piraeus Medical, and WFITN., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Endovascular thrombectomy (EVT) is the standard treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Although > 70% of patients in the trials assessing EVT for AIS-LVO had successful recanalization, only a third ultimately achieved favorable outcomes. A "no-reflow" phenomenon due to distal microcirculation disruption might contribute to such suboptimal outcomes. Combining intra-arterial (IA) tissue plasminogen activator (tPA) and EVT to reduce the distal microthrombi burden was investigated in a few studies. We present a pooled-data meta-analysis of the existing evidence of this combinatorial treatment., Methods: We followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) recommendations. We aimed to include all original studies investigating EVT plus IA tPA in AIS-LVO patients. Using R software, we calculated pooled odds ratios (ORs) with corresponding 95% confidence intervals (CI). A fixed-effects model was adopted to evaluate pooled data., Results: Five studies satisfied the inclusion criteria. Successful recanalization was comparable between the IA tPA and control groups at 82.9% and 82.32% respectively. The 90-day functional independence was similar between both groups (OR= 1.25; 95% CI= 0.92-1.70; P= 0.154). Symptomatic intracranial hemorrhage (sICH) was also comparable between both groups (OR= 0.66; 95% CI= 0.34-1.26; P= 0.304)., Conclusion: Our current meta-analysis does not show significant differences between EVT alone and EVT plus IA tPA in terms of functional independence or sICH. However, with the limited number of studies and included patients, more randomized controlled trials (RCTs) are needed to further investigate the benefits and safety of combined EVT and IA tPA., Competing Interests: Declaration of Competing Interest The Authors declare that they did not receive any financial and personal relationships with other people or organizations that could inappropriately influence (bias) this work., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: Competing interests: None declared.

Background: Early neurological improvement (ENI) is a potential predictor for 90-day outcomes following mechanical thrombectomy for acute ischemic stroke (AIS). We performed a systematic review and meta-analysis to better understand whether ENI can be used as a surrogate for long-term outcomes following mechanical thrombectomy for AIS., Methods: Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, MEDLINE, and Embase. ENI definition, including timing and degree of improvement on the National Institutes of Health Stroke Scale (NIHSS), was catalogued for each included study. Outcomes of interest included 90-day modified Rankin Scale (mRS) 0-2, symptomatic intracranial hemorrhage (sICH), and mortality. We calculated pooled ORs and their corresponding 95% confidence intervals (CI) for all definitions of ENI., Results: We included nine studies with 2355 patients in our analysis. ENI definitions included improvement in NIHSS of 8 points, 4 points, 12%, and 30% or greater. There was a significant association between ENI and mRS 0-2 rates (OR 8.62, 95% CI 4.86 to 15.29; p<0.001). Significance of the association was maintained across all definitions (p<0.001). Moreover, achieving ENI was a significant predictor of reduced odds for reported sICH rates (OR 0.11, 95% CI 0.06 to 0.21; p<0.001). There was a significant association between ENI and reduction in mortality rates (OR 0.09, 95% CI 0.05 to 0.15; p<0.001)., Conclusions: Broadly defined, ENI is a promising predictor of good functional outcome at 90 days and is associated with lower rates of mortality and sICH., Competing Interests: Competing interests: DFK holds equity in Nested Knowledge, Superior Medical Editors, and Conway Medical, Marblehead Medical; is a consultant for MicroVention, Medtronic, Balt, and Insera Therapeutics; Data Safety Monitoring Board for Vesalio; and receives royalties from Medtronic., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Endovascular therapy (EVT) represents the standard of care for eligible patients with acute ischemic stroke (AIS) and large vessel occlusion. To better understand differences in baseline characteristics and outcomes between males and females following EVT, we conducted a systematic review and meta-analysis., Methods: We identified, using the Nested Knowledge AutoLit platform, prospective studies that reported 90-day outcomes in males and females treated with EVT for AIS. The primary outcome of interest was 90-day modified Rankin Scale (mRS) 0-2. Secondary outcome variables included mRS 0-1, symptomatic intracranial hemorrhage (sICH), thrombolysis in cerebral infarction (TICI) score 2b-3, and mortality. Using R software version 4.1.2, we calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI)., Results: We included 10 studies with 10,209 patients. There was no difference between males and females in rate of mRS 0-2 (OR= 1.16; 95% CI= 0.87-1.56; P-value= 0.316); however, after removing outliers, males had higher rates of mRS 0-2 (OR= 1.40; 95% CI= 1.19-1.66; P-value< 0.001). Similar results were reported for mRS 0-1 (OR= 1.21; 95% CI= 0.93-1.56; P-value= 0.15), after removing outliers (OR= 1.32; 95% CI= 1.17-1.50; P-value< 0.001). There was no difference between males and females in rate of sICH (OR= 0.89; 95% CI= 0.74-1.08; P-value= 0.246), mortality (OR= 0.88; 95% CI= 0.74-1.05; P-value= 0.15), or TICI 2b-3 (OR= 1.19; 95% CI= 0.85-1.67; P-value= 0.309)., Conclusions: Males tend to experience better outcomes following EVT for AIS, even in the setting of similar reperfusion. The mechanisms underlying this phenomenon remain unclear, and further research is warranted. EVT remains a safe and effective option for both males and females with AIS., Competing Interests: Declaration of competing interest D.F.K. holds equity in Nested Knowledge, Superior Medical Editors, and Conway Medical, Marblehead Medical; a consultant for MicroVention, Medtronic, Balt, and Insera Therapeutics; Data Safety Monitoring Board for Vesalio; and receiving royalties from Medtronic. A.A.R. serves in the CEC committee for trials sponsored by Boston Scientific and has participated in advisory board meetings for Astra Zeneca and Novo Nordisk., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Artificial intelligence (AI)-based algorithms have been developed to facilitate rapid and accurate computed tomography angiography (CTA) assessment in proximal large vessel occlusion (LVO) acute ischemic stroke, including internal carotid artery and M1 occlusions. In clinical practice, however, the detection of medium vessel occlusion (MeVO) represents an ongoing diagnostic challenge in which the added value of AI remains unclear., Purpose: To assess the diagnostic performance of AI platforms for detecting M2 occlusions., Methods: Studies that report the diagnostic performance of AI-based detection of M2 occlusions were screened, and sensitivity and specificity data were extracted using the semi-automated AutoLit software (Nested Knowledge, MN) platform. STATA (version 16 IC; Stata Corporation, College Station, Texas, USA) was used to conduct all analyses., Results: Eight studies with a low risk of bias and significant heterogeneity were included in the quantitative and qualitative synthesis. The pooled estimates of sensitivity and specificity of AI platforms for M2 occlusion detection were 64% (95% CI, 53 to 74%) and 97% (95% CI, 84 to 100%), respectively. The area under the curve (AUC) in the SROC curve was 0.79 (95% CI, 0.74 to 0.83)., Conclusion: The current performance of the AI-based algorithm makes it more suitable as an adjunctive confirmatory tool rather than as an independent one for M2 occlusions. With the rapid development of such algorithms, it is anticipated that newer generations will likely perform much better., Competing Interests: Declaration of Competing Interest KMK works for and holds equity in Nested Knowledge, Inc., works for Conway Medical LLC, and holds equity in Superior Medical Experts, Inc. JJH is a consultant for Medtronic and MicroVention and a member of the Medical and Scientific Advisory Board for iSchemaView. DFK holds equity in Nested Knowledge, Superior Medical Editors, and Conway Medical, Marblehead Medical; a consultant for MicroVention, Medtronic, Balt, and Insera Therapeutics; Data Safety Monitoring Board for Vesalio; and receiving royalties from Medtronic. AvdL received research support from Stryker, Medtronic, Penumbra and Cerenovus., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Clinical trials addressing large core acute ischemic stroke (AIS) are ongoing across multiple international groups. Future development of clinical guidelines depends on meta-analyses of these trials calling for a degree of homogeneity of elements across the studies. This common data element study aims to provide an overview of key features of pertinent large core infarct trials., Methods: PubMed and ClinicalTrials.gov databases were screened for published and ongoing clinical trials assessing mechanical thrombectomy in patients with AIS with large core infarct. Nested Knowledge AutoLit living review platform was utilized to categorize primary and secondary outcomes as well as inclusion and exclusion criteria for patient selection in the trials., Results: The most reported data element was ASPECTS score but with varied definitions of what constitutes large core. Non-utility-weighted modified Rankin score (mRS) was reported in 6/7 studies as the primary outcome, while the utility-weighted mRS was the outcome of interest in the TESLA trial, all of them at the 3 months mark, with only LASTE looking for mRS shift at the 6 months mark. Secondary outcomes had more variations. Mortality is reported separately only in 4/7 trials, all at the 3‑month mark. Additionally, the TENSION trial reported the frequency of serious adverse events, including mortality, at the 1‑week and 12-month mark., Discussion: Overall, in large core trials there is a large degree of heterogeneity in the collected data elements. Differences in definition and timepoints render reaching a unified standard difficult, which hinders high quality meta-analyses and cohesive evidence-driven synthesis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Objectives: Patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) in the late window (6-24 hours) can be evaluated with CT perfusion (CTP) or with noncontrast CT (NCCT) only. Whether outcomes differ depending on the type of imaging selection is unknown. We conducted a systematic review and meta-analysis comparing outcomes between CTP and NCCT for EVT selection in the late therapeutic window., Methods: This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines. A systematic literature review of the English language literature was conducted using Web of Science, Embase, Scopus, and PubMed databases. Studies focusing on late-window AIS undergoing EVT imaged through CTP and NCCT were included. Data were pooled using a random-effects model. The primary outcome of interest was rate of functional independence, defined as modified Rankin scale 0-2. The secondary outcomes of interest included rates of successful reperfusion, defined as thrombolysis in cerebral infarction 2b-3, mortality, and symptomatic intracranial hemorrhage (sICH)., Results: Five studies with 3,384 patients were included in our analysis. There were comparable rates of functional independence (odds ratio [OR] 1.03, 95% CI 0.87-1.22; p = 0.71) and sICH (OR 1.09, 95% CI 0.58-2.04; p = 0.80) between the 2 groups. Patients imaged with CTP had higher rates of successful reperfusion (OR 1.31, 95% CI 1.05-1.64; p = 0.015) and lower rates of mortality (OR 0.79, 95% CI 0.65-0.96; p = 0.017)., Discussion: Although recovery of functional independence after late-window EVT was not more common in patients selected by CTP when compared with patients selected by NCCT only, patients selected by CTP had lower mortality., (© 2023 American Academy of Neurology.)

Background: Successful recanalization after endovascular thrombectomy serves as the primary endpoint in clinical trials and is a crucial predictor of long-term outcomes. Radiographic outcomes for various interventions have been shown to vary based on the type of interpreter, including the site interventionalist compared with an independent reader., Objective: To compare angiographic outcomes in stroke thrombectomy procedures based on the type of reader., Methods: A systematic literature search was conducted in Medline, EMBASE, Scopus, and Web-of-Science through February 2022. We included primary studies that reported core laboratory-read and operator angiographic outcomes after mechanical thrombectomy for ischemic stroke. Furthermore, study-defined successful recanalization data were collected., Results: Eight studies were included with 4797 patients, 51.2% of whom were male. Four thousand, four hundred and thirty-one patients had core readings, and 4211 had operator readings. Study-defined successful recanalization was significantly higher for operator (84%, 3543/4211) examinations than for core laboratory-read (78.4%, 3476/4431) examinations (p<0.001; OR=1.462, 95% CI 1.175 to 1.819). The modified Thrombolysis in Cerebral Infarction (mTICI) scale score of ≥2 b was higher for operator (85%, 3341/3929) examinations than for core laboratory-read (78.6%, 3107/3952) examinations (p<0.001; OR=1.349, 95% CI 1.071 to 1.701). mTICI 3 was significantly higher for operator (54.6%, 1000/1832) examinations than for core laboratory-read (39.9%, 731/1832) examinations (p<0.001; OR=1.823, 95% CI 1.598 to 2.081)., Conclusion: Operator angiographic reads are statistically significantly higher than core laboratory-read readings following stroke thrombectomy, especially for complete recanalization. These differences should be considered when interpreting reports of angiographic outcomes after thrombectomy., Competing Interests: Competing interests: DFK has the following conflicts: ownership in Nested Knowledge, Inc., Superior Medical Experts, Inc., Conway Medical LLC; research support from: Microvention, Balt USA, Medtronic. RK reports NIH funding (R01 NS076491, R43 NS110114, and R44 NS107111); is a research consultant for Cerenovus, Insera Therapeutics LLC, Marblehead Medical LLC, Microvention Inc, MIVI Neuroscience Inc, Neurogami Medical Inc, and Triticum Inc; and has stock in Neurosigma Inc (money paid to institution)., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Patients with atrial fibrillation (AF) treated with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) have been reported to experience worse outcomes compared with patients without AF., Objective: To assess differences between patients with AF and their counterparts without AF treated with MT for AIS, focusing on safety outcomes, clinical outcomes, and baseline characteristics in both groups., Data Sources: A systematic literature review of the English language literature from inception to July 14, 2022, was conducted using Web of Science, Embase, Scopus, and PubMed databases., Study Selection: Studies that focused on patients with and without AF treated with MT for AIS were included. Multiple reviewers screened studies to identify studies included in analysis., Data Extraction and Synthesis: Data were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline to ensure accuracy. Data were pooled using a random-effects model., Main Outcomes and Measures: The primary outcome of interest was rate of modified Rankin Scale (mRS) scores of 0 to 2 at 90 days. Secondary outcomes of interest included rates of successful reperfusion, defined as thrombolysis in cerebral infarction (TICI) scores of 2b to 3, 90-day mortality, symptomatic intracranial hemorrhage (SICH), and baseline patient characteristics., Results: Of 1696 initially retrieved studies, 10 studies were included, with 6543 patients. Patients with AF were a mean of 10.17 (95% CI, 8.11-12.23) years older (P < .001) and had higher rates of hypertension (OR, 1.89 [95% CI, 1.57-2.27]; P < .001) and diabetes (OR, 1.16 [95% CI, 1.02-1.31]; P = .02). Overall, there were comparable rates of mRS scores of 0 to 2 between patients with AF and patients without AF (odds ratio [OR], 0.72 [95% CI, 0.47-1.10]; P = .13), with significant heterogeneity among the included studies. After sensitivity analysis, the rate of mRS scores of 0 to 2 was significantly lower among patients with AF (OR, 0.65 [95% CI, 0.52-0.81]; P < .001). Successful reperfusion rates were similar between the groups (OR, 1.11 [95% CI, 0.78-1.58]; P = .57). The rate of SICH was similar between groups (OR, 1.05 [95% CI, 0.84-1.31]; P = .68). Mortality was significantly higher in the AF group (OR, 1.47 [95% CI, 1.12-1.92]; P = .005)., Conclusions and Relevance: In this systematic review and meta-analysis, patients with AF experienced worse 90-day outcomes, even in the setting of similar rates of successful reperfusion. This was likely associated with greater age and greater rates of comorbidities among patients with AF.

Background: Previous studies comparing a direct aspiration first pass technique (ADAPT) and stent retrievers have inconsistent methodologies and data reporting, limiting the ability to accurately assimilate data from different studies that would inform treatment of acute ischemic stroke (AIS) treatment., Objective: To conduct a systematic review to discuss and compare the findings of all relevant meta-analysis studies comparing the efficacy of the ADAPT and stent retriever techniques., Methods: The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), where meta-analyses comparing the efficacy of the ADAPT technique and stent retrievers in the treatment of AIS were included. We extracted all relevant data from the included studies and assessed the quality of the included meta-analyses using the Assessment of Multiple Systematic Review (AMSTAR-2)., Results: Seven relevant studies met our inclusion criteria and were suitable for the qualitative synthesis. All included studies obtained data from randomized controlled trials (RCTs) and observational investigations (including levels II, III, and IV). At the same time, none of them used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for quality assessment. In accordance with AMSTAR-2, two studies were rated 'high', while the other five were rated 'moderate'., Conclusions: Present evidence is insufficient to clarify the superiority of one modality over the other. Further RCTs on this comparison must be conducted prior to designing further meta-analyses or making conclusive interpretations. Procedure duration and cost should be taken into consideration for any future studies., Competing Interests: Competing interests: KMK works for, and holds equity in, Nested Knowledge, Inc., works for Conway Medical LLC, and holds equity in Superior Medical Experts, Inc. JJH is a consultant for Medtronic and MicroVention and a member of the Medical and Scientific Advisory Board for iSchemaView. DFK has the following conflicts: Ownership in Nested Knowledge, Inc., Superior Medical Experts, Inc., Conway Medical LLC; research support from Microvention, Balt USA, Medtronic., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The presence of an outer shell has been recently described as a common feature of acute ischemic stroke (AIS) thrombi. We performed a systematic review of the current literature on shell genesis, structure, and clinical significance., Methods: Following PRISMA guidelines, we searched Ovid Cochrane Central Register of Controlled Trials, Embase, Medline, Scopus, and Web of Science for studies reporting the composition and structure of AIS thrombi and clot analogs. Identified studies were added to Covidence software for primary screening. Two reviewers independently screened titles and abstracts followed by full-text screening., Results: From 1290 identified studies, 10 were included in this review. Studies using histology/immunohistochemistry/immunofluorescence described fibrin, platelets, von Willebrand factor, and neutrophil extracellular traps as the main components of the shell. Scanning electron microscopy demonstrated a dense, compact fibrin/platelet-rich shell, and a core rich in polyhedrocytes. Microfluidics studies identified highly activated P-selectin-positive platelets and fibrin forming the core while secondary agonists adenosine diphosphate and thromboxane, along with loosely packed P-selectin-negative platelets constituted the shell., Conclusions: The composition, compaction, and integrity of the shell may impact thrombolysis and revascularization outcomes. The preponderance of studies supported this conclusion., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Most studies define the technical success of endovascular thrombectomy (EVT) as a Thrombolysis in Cerebral Infarction (TICI) revascularization grade of 2b or higher. However, growing evidence suggests that TICI 3 is the best angiographic predictor of improved functional outcomes. To assess the association between successful TICI revascularization grades and functional independence at 90 days, we performed a systematic review and network meta-analysis of thrombectomy studies that reported TICI scores and functional outcomes, measured by the modified Rankin Scale, using the semi-automated AutoLit software platform. Forty studies with 8691 patients were included in the quantitative synthesis. Across TICI, modified TICI (mTICI), and expanded TICI (eTICI), the highest rate of good functional outcomes was observed in patients with TICI 3 recanalization, followed by those with TICI 2c and TICI 2b recanalization, respectively. Rates of good functional outcomes were similar among patients with either TICI 2c or TICI 3 grades. On further sensitivity analysis of the eTICI scale, the rates of good functional outcomes were equivalent between eTICI 2b50 and eTICI 2b67 (OR 0.81, 95% CI 0.52 to 1.25). We conclude that near complete or complete revascularization (TICI 2c/3) is associated with higher rates of functional outcomes after EVT., Competing Interests: Competing interests: KMK works for and holds equity in Nested Knowledge Inc, works for Conway Medical LLC, and holds equity in Superior Medical Experts Inc. JJH is a consultant for Medtronic and MicroVention and a member of the Medical and Scientific Advisory Board for iSchemaView., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: First pass effect (FPE) is defined as achieving modified treatment in cerebral infarction (mTICI) grade 2c/3 reperfusion from the first pass and is associated with more favorable outcomes. We aimed to compare FPE and non-FPE using a large database and further compare first-pass mTICI 2b with multiple passes mTICI 3., Methods: A retrospective cohort study of acute ischemic stroke patients who received mechanical thrombectomy at a high-volume center was performed. Baseline characteristics and outcomes including rates of discharge and 90-day functional independence (modified Rankin Scale ≤2), mortality, symptomatic, and asymptomatic intracerebral hemorrhage were compared., Results: Of the 637 patients included, 294 achieved FPE; 161 patients had multiple passes mTICI 3 and 36 had first pass mTICI 2b. Propensity-score matching resulted in 211 matched pairs for FPE vs non-FPE, and 30 matched pairs for multiple passes mTICI 3 vs first pass mTICI 2b. The FPE group had significantly more instances of discharge (33.6% vs 19.4%, p  = 0.001) and 90-day functional independence (51.7% vs 40.8%, p  = 0.032), and lower rates of mortality (18.0% vs 27.5%, p  = 0.027) compared to non-FPE. There was no significant difference between first pass mTICI 2b and multiple passes mTICI 3 concerning any studied outcomes., Conclusions: First pass mTICI 2c/3 is safer and is associated with higher rates of functional independence. We did not observe a significant difference between first pass mTICI 2b and multiple passes mTICI 3. The limitations of this study prevent us from drawing conclusions related to the difference between them and calls for future large-scale studies to explore that further.

Background: To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome., Methods: Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications., Results: A total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age >60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p<0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome., Conclusion: There is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute ischemic stroke (AIS) imposes a major healthcare burden. It is hypothesized that bacterial infection could influence atherosclerosis and thrombus formation, potentially contributing to AIS. Objectives: We aim to systematically review all studies that have investigated the presence of bacterial signatures within thrombi retrieved following mechanical thrombectomy (MT) procedures in patients with AIS. Design: This systematic review is designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist. Data sources and methods: A comprehensive search was conducted in the Web of Sciences, PubMed, Scopus, and Embase databases to identify relevant studies. Results: The literature search and screening included 11 studies involving 674 patients, with 414 (61.4%) being male and 260 (38.6%) females. Among all the patients, 393 (58.3%) were positive for bacterial presence in their retrieved thrombi. The most utilized technique for bacterial signature detection was bacterial DNA extraction followed by polymerase chain reaction amplification of the 16S rRNA gene sequence. Staphylococcus aureus was the most studied bacteria among the studies analyzed. Conclusion: Bacterial infections and the presence of bacteria within thrombi may significantly contribute to AIS by initiating or exacerbating atherosclerosis or thrombosis. Understanding the mechanisms by which bacteria affect vascular health is crucial for developing effective preventive and therapeutic strategies for stroke patients. [ABSTRACT FROM AUTHOR]

Background: Early neurological deterioration (END) is a potential predictor for 90-day outcomes following mechanical thrombectomy for acute ischemic stroke (AIS). We performed a systematic review and meta-analysis to better understand whether END can be used as a surrogate for long-term outcomes. Methods: Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, MEDLINE, and Embase. END definition was cataloged for each included study. Outcomes of interest included 90-day modified Rankin Scale (mRS) 0–2, symptomatic intracranial hemorrhage (sICH), mortality, and thrombolysis in cerebral infarction (TICI) 2b-3. We calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI) for all definitions of END. Results: We included seven studies with 2992 patients in our analysis. There was a significant, inverse association with END and mRS 0–2 rates (OR = 0.15; 95% CI = 0.08–0.29; P-value< 0.001). Moreover, END was a significant predictor of increased odds for reported sICH rates (OR = 16.37; 95% CI = 7.66–34.99; P-value< 0.001). Furthermore, there was a significant association between END and increase in mortality rates (OR = 6.79; 95% CI = 2.62–17.62; P-value< 0.001). There was no significant association between END and rates of TICI 2b-3 (OR = 0.53; 95% CI = 0.27–1.05; p = 0.069). Conclusions: Broadly defined, END holds value as a potential predictor of rates of mRS 0–2 at 90 days and is associated with higher rates of mortality and sICH, but had no correlation with TICI 2b-3. [ABSTRACT FROM AUTHOR]

Background: Wake-up stroke represents a significant challenge in acute treatment and care. Thrombolysis has been extensively studied in the wake-up stroke population. However, mechanical thrombectomy in wake-up stroke exclusively has not been well studied. We performed a systematic review and meta-analysis to assess the clinical and functional outcomes of patients undergoing mechanical thrombectomy for wake-up stroke. Methods: We performed a systematic review of the literature using publically accessible databases. Data extraction was completed using Nested Knowledge AutoLit software. Outcomes of interest included modified Rankin Scale (mRS) 0–2, mortality, symptomatic intracerebral hemorrhage (sICH), and thrombolysis in cerebral infarction (TICI) score 2b/3. Statistical analysis was performed using R software version 4.1.2. Results: A total of 12 studies were included in our study with a total of 510 patients included. Patients with wake-up stroke were found to have good functional outcome (mRS 0–2) in 46.2% of patients and successful reperfusion (TICI 2b/3) was seen in 83.5% of patients. Mortality was observed in 20.4% of patients with sICH seen in 8.3%. Conclusion: Mechanical thrombectomy for patients with wake-up stroke was found to have favorable rates of good functional outcomes and relatively low rates of adverse events. [ABSTRACT FROM AUTHOR]

Background and Purpose: The Alberta Stroke Program Early CT Score (ASPECTS) is a widely used scoring system for evaluating ischemic stroke to determine therapeutic strategy. However, there is variation in the interobserver agreement of ASPECTS. This systematic review and meta‐analysis aimed to investigate the interobserver agreement of total and regional ASPECTS. Methods: A comprehensive search was conducted in the Web of Sciences, PubMed, and Scopus databases to identify relevant studies. Inclusion criteria were studies of noncontrast CT performed within 24 hours of ischemic stroke in the middle cerebral artery territory. Results: A total of 20 studies, with 3482 patients, reporting interobserver agreement of total and regional ASPECTS were included in the meta‐analysis. The interobserver agreement for total ASPECTS in studies using Kappa coefficient (κ) analysis was substantial (κ =.67, 95% confidence interval [CI]:.57‐.78). In studies using intraclass correlation coefficient (ICC) analysis, agreement was excellent (ICC =.84, 95% CI:.77‐.90). Interobserver agreement was higher in studies in which the observer was unblinded to clinical scenario in both groups (κ =.74, 95% CI:.59‐.89, and ICC =.82, 95% CI:.79‐.85). Per‐region analysis showed that the caudate nucleus had the highest agreement (κ =.68, 95% CI:.60‐.76, and ICC =.84, 95% CI:.74‐.93), while M2 and internal capsule in Kappa studies (κ =.45, 95% CI:.34‐.55 and κ =.47, 95% CI:.28‐.66), and M4 and internal capsule in ICC studies (ICC =.54, 95% CI:.43‐.64 and ICC =.55, 95% CI:.18‐.91) had the lowest agreement. Conclusion: This meta‐analysis demonstrates substantial to excellent interobserver agreement for total ASPECTS, which supports using this method for stroke treatment. However, findings emphasize the need to consider interobserver agreement in specific regions of ASPECTS for treatment decisions. [ABSTRACT FROM AUTHOR]

Background: Young patients experience acute ischemic stroke (AIS) at much lower rates than their older counterparts. We performed a systematic review and meta-analysis to assess the question regarding outcomes and clinical characteristics of young stroke patients who underwent mechanical thrombectomy for AIS. Methods: Following PRISMA guidelines, a systematic review of the literature was conducted using the databases PubMed, MEDLINE, and Embase. The primary outcome of interest was 90-day modified Rankin Scale (mRS) 0–2. Secondary outcome variables included rate of successful reperfusion (TICI 2b/3), symptomatic intracerebral hemorrhage (sICH), and mortality. Using R software version 4.1.2, we calculated pooled event rates and their corresponding 95% confidence intervals (CI) for all outcomes. Results: Our analysis included eight studies with a total of 1903 patients. Definitions of young patients included age ranges of 18–49/50 years, 18–54/55 years, and 18–64/65 years. Functional independence was achieved in 62.0% of the patients, with an overall mortality of 9.0%. Moreover, successful reperfusion was achieved in 82.0% of the patients with sICH rates of 5.7%. There was significant heterogeneity among different analyses, which could not be attributed to the differences of the definition of young patients. Conclusions: Following mechanical thrombectomy for AIS, patients aged 18–65 years achieved relatively high rates of functional independence and successful reperfusion and low rates of mortality and sICH. Clinical Perspective In this systematic review and meta-analysis of eight studies, we examined outcomes in young stroke patients, aged 18–65 years old, following mechanical thrombectomy for acute ischemic stroke. We found that young patients achieved high rates of functional independence, high rates of successful reperfusion, and low rates of mortality and symptomatic intracerebral hemorrhage. While there have been several papers examining outcomes following mechanical thrombectomy for acute ischemic stroke in young patients, the results of these studies have yet to be pooled together in a meta-analysis. Our results indicate that young patients have good outcomes following mechanical thrombectomy. Further studies that examine these outcomes are warranted so that a higher-powered analysis can be performed to better informed clinicians regarding outcomes in this patient age-group cohort. [ABSTRACT FROM AUTHOR]

Background Risks and benefits of intravenous thrombolysis (IVT) in patients undergoing mechanical thrombectomy (MT) have been a topic of interest. However, IVT's specific effects on stent retriever (SR) and aspiration thrombectomy (ASP) outcomes remain largely unexplored. In this meta-analysis, we aimed to investigate the effects of IVT on SR and ASP thrombectomy outcomes. Methods In accordance with PRISMA guidelines, a systematic literature review was conducted using Medline, Embase, Scopus, Web of Science, and Cochrane Center of Clinical Trials databases. Outcomes of interest included successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b), modified first pass efficacy (mFPE), functional independence (modified Rankin Scale (mRS) ≤2), symptomatic intracranial hemorrhage (sICH), and embolization to new territories (ENT). Results Four randomized controlled trials with 1176 patients were included. SR and ASP resulted in similar mTICI ≥2b, mFPE, and mRS 0-2 rates in patients with and without IVT administration. SR without IVT was associated with a significantly lower rate of mFPE compared with the SR+IVT (RR 0.85, 95% CI 0.74 to 0.97). Furthermore, ASP without IVT resulted in a lower rate of mRS 0-2 than the ASP+IVT with a strong trend towards significance (RR 0.78, 95% CI 0.60 to 1.01). Finally, bridging therapy did not increase sICH and ENT rates after ASP or SR thrombectomy. Conclusions Our findings suggest that SR and ASP thrombectomy have comparable safety and efficacy profiles, regardless of prior IVT administration. Additionally, our results indicate that the addition of IVT may improve certain efficacy outcomes based on the employed first-line MT technique. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to evaluate the effect of mechanical thrombectomy (MT) on the incidence of poststroke cognitive impairment (PSCI) in anterior circulation stroke. Methods: Literature research was performed on PubMed/OVID/Cochrane CENTRAL for studies published in 2015–2022. A review of the references of the included papers was performed for further eligible articles. Clinical characteristics, NIHSS, dementia tests, and outcomes were recorded. The exclusion criteria were nonhuman and non-English. Studies qualities were assessed with MINORS/RoB2 and GRADE. A meta-analysis was performed using the standardized mean difference (Cohen's d) to measure effect size. Results: Four studies were included in the systematic review after screening 749 articles. No significant differences were found for age and gender (years: 66.70 ± 11.14 vs. 67.59 ± 10.11, p = 0.37; male 53.8% vs. 56.4%, p = 0.57). MT patients had a more severe stroke than that of the control group (NIHSS: 14.70 ± 4.31 vs. 11.17 ± 4.12; p < 0.0001). The control group consisted of medical therapy-alone patients in all studies. I2 was 76.95%, and Q was 43.4%. MT patients have better performance in overall cognition (d = 0.33 [0.074–0.58]) and in several cognitive domains than in the control group (TMT-A, d = 0.37 [0.04–0.70]; TMT-B, d = 0.35 [0.12–0.58]; digit span test [backward], d = 0.61 [0.18–1.06]; colored progressive matrices, d = 0.48 [0.05–0.91]; Stroop test [word reading], d = 0.60 [0.17–1.03]; color naming, d = 0.51 [0.08–0.94]; Rey-Osterrieth Complex Figure [immediate recall], d = 0.79 [0.35–1.23]; Rey Auditory Verbal Learning Test [immediate recall], d = 0.79 [0.36–1.23]; delayed recall, d = 0.46 [0.035–0.89]; and MOCA, d = 0.46 [−0.04 to 0.96]). Medical therapy patients had a higher score in coping strategy than MT patients (COPE-28 acceptance, d = −1.00 [−1.53 to −0.48]). Conclusions: The incidence of PSCI is lower in MT patients than in the control group. [ABSTRACT FROM AUTHOR]

Background Flow diverters have been widely used in clinical practice for more than a decade. However, most outcome data are limited to 1 year timepoints. This study aims to offer meta-analysis data on long-term (>1 year) safety and effectiveness results for patients with aneurysms treated with flow diverters. Methods PubMed, Web of Science, Embase, and SCOPUS were searched up to February 24, 2022 using the AutoLit platform. We included primary studies assessing the long-term outcomes for flow diverter devices to manage unruptured internal carotid artery aneurysms with a follow-up period of >1 year. The metaanalysis was carried out using Comprehensive Meta-Analysis software (CMA). Results Eleven studies were included in the metaanalysis. The pooled occlusion rates after flow diversion treatment for unruptured intracranial brain aneurysms were 77%, 87.4%, 84.5%, 89.4%, 96% for 1 year, 1-2 years, 2 years, 3 years, and 5 years follow-up, respectively. The in-stent stenosis rate was 4.8% and the retreatment rate for the long-term follow-up period was 5%. No delayed rupture of the aneurysm was reported, and there was one case of delayed ischemic stroke. The sensitivity analysis of the prospective studies showed a complete occlusion rate of 83.5% and 85.2% for 1 and 3 years of follow-up, respectively. Conclusion Flow diverters are safe and effective in short-and long-term follow-up and rarely cause serious delayed side effects. [ABSTRACT FROM AUTHOR]