Project description:BackgroundEndovascular thrombectomy (EVT) has emerged as the established standard of care for the treatment of anterior circulation large-vessel occlusion (LVO). However, its benefits remain unclear in specific patient populations. Herein, we present an updated systematic review and meta-analysis aimed at thoroughly assessing the effectiveness and safety of combining EVT with medical treatment (MT) compared with MT alone.MethodsThis systematic review was performed in accordance with the PRISMA guideline. The MEDLINE, Embase, and Cochrane databases were systematically searched to identify relevant articles published until December 30, 2023. The inclusion criteria restricted articles to randomized clinical trials (RCTs). We pooled odds ratios (OR) and their respective 95% confidence intervals (CIs).ResultsFifteen RCTs involving 3897 patients were included in the study. EVT plus MT was associated with a significant reduction in disability at 90 days (OR = 1.91, [1.61-2.26]), improved functional independence (modified Rankin Scale [mRS] 0-2) (OR = 2.19 [1.81-2.64]), excellent functional outcomes (mRS 0-1) (OR = 2.37, [1.45-3.87]), improved independent ambulation (mRS 0-3) (OR = 2.17, [1.75-2.69]), and higher rates of partial/complete recanalization (OR = 2.18, [1.66-2.87] compared with EVT. Efficacy outcomes for both large and small infarct cores were statistically favorable following EVT. Safety outcomes showed comparable rates, except for intracerebral and subarachnoid hemorrhage, which favored MT alone.ConclusionThis meta-analysis supports the use of EVT plus MT as the standard of care for acute ischemic stroke patients with LVO of any infarct core size, as it offers substantial improvements in functional outcomes and recanalization. Safety considerations, particularly the risk of hemorrhage, warrant careful patient selection. These findings provide valuable insights for optimizing stroke management protocols and enhancing patient outcomes.

Project description:BackgroundRecent randomized trials have suggested that endovascular thrombectomy (EVT) alone may provide similar functional outcomes as the current standard of care, EVT combined with intravenous alteplase treatment, for acute ischemic stroke secondary to large vessel occlusion. We conducted an economic evaluation of these 2 therapeutic options.MethodsWe constructed a decision analytic model with a hypothetical cohort of 1000 patients to assess the cost-effectiveness of EVT with intravenous alteplase treatment versus EVT alone for acute ischemic stroke secondary to large vessel occlusion from both the societal and public health care payer perspectives. We used studies and data published in 2009-2021 for model inputs, and acquired cost data for Canada and China, representing high- and middle-income countries, respectively. We calculated incremental cost-effectiveness ratios (ICERs) using a lifetime horizon and accounted for uncertainty using 1-way and probabilistic sensitivity analyses. All costs are reported in 2021 Canadian dollars.ResultsIn Canada, the difference in quality-adjusted life-years (QALYs) gained between EVT with alteplase and EVT alone was 0.10 from both the societal and health care payer perspectives. The difference in cost was $2847 from a societal perspective and $2767 from the payer perspective. In China, the difference in QALYs gained was 0.07 from both perspectives, and the difference in cost was $1550 from the societal perspective and $1607 from the payer perspective. One-way sensitivity analyses showed that the distributions of modified Rankin Scale scores at 90 days after stroke were the most influential factor on ICERs. For Canada, compared to EVT alone, the probability that EVT with alteplase would be cost-effective at a willingness-to-pay threshold of $50 000 per QALY gained was 58.7% from a societal perspective and 58.4% from a payer perspective. The corresponding values for at a willingness-to-pay threshold of $47 185 (3 times the Chinese gross domestic product per capita in 2021) were 65.2% and 67.4%.InterpretationFor patients with acute ischemic stroke due to large vessel occlusion eligible for immediate treatment with both EVT alone and EVT with intravenous alteplase treatment, it is uncertain whether EVT with alteplase is cost-effective compared to EVT alone in Canada and China.

Project description:ImportanceWhether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain.ObjectiveTo describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect.Design, setting, and participantsAn exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022.InterventionEVT vs MM.Main outcomes and measuresPrimary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI.ResultsAmong 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled.Conclusion and relevanceIn this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased.Trial registrationClinicalTrials.gov Identifier: NCT03876457.

Project description:Background and purposeEarly identification of large vessel occlusions (LVO) and timely recanalization are paramount to improved clinical outcomes in acute ischemic stroke. A stroke assessment that maximizes sensitivity and specificity for LVOs is needed to identify these cases and not overburden the health system with unnecessary transfers. Machine learning techniques are being used for predictive modeling in many aspects of stroke care and may have potential in predicting LVO presence and mechanical thrombectomy (MT) candidacy.MethodsIschemic stroke patients treated at Loyola University Medical Center from July 2018 to June 2019 (N = 286) were included. Thirty-five clinical and demographic variables were analyzed using machine learning algorithms, including logistic regression, extreme gradient boosting, random forest (RF), and decision trees to build models predictive of LVO presence and MT candidacy by area of the curve (AUC) analysis. The best performing model was compared with prior stroke scales.ResultsWhen using all 35 variables, RF best predicted LVO presence (AUC = 0.907 ± 0.856-0.957) while logistic regression best predicted MT candidacy (AUC = 0.930 ± 0.886-0.974). When compact models were evaluated, a 10-feature RF model best predicted LVO (AUC = 0.841 ± 0.778-0.904) and an 8-feature RF model best predicted MT candidacy (AUC = 0.862 ± 0.782-0.942). The compact RF models had sensitivity, specificity, negative predictive value and positive predictive value of 0.81, 0.87, 0.92, 0.72 for LVO and 0.87, 0.97, 0.97, 0.86 for MT, respectively. The 10-feature RF model was superior at predicting LVO to all previous stroke scales (AUC 0.944 vs 0.759-0.878) and the 8-feature RF model was superior at predicting MT (AUC 0.970 vs 0.746-0.834).ConclusionRandom forest machine learning models utilizing clinical and demographic variables predicts LVO presence and MT candidacy with a high degree of accuracy in an ischemic stroke cohort. Further validation of this strategy for triage of stroke patients requires prospective and external validation.

Project description:BackgroundEmergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy.MethodsThe blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical analysis of plasma proteomics used independent sample t tests, correlations, linear regression, and robust regression models to determine network signaling and predictors of clinical outcomes. Data and network analyses were performed using IBM SPSS Statistics, SAS v 9.4, and STRING V11.ResultsIncreased systemic (p<0.001) and intracranial (p=0.013) levels of VCAM1 were associated with the presence of hypertension. Intracranial VCAM1 was positively correlated to both infarct volume (p=0.032; r=0.34) and edema volume (p=0.026; r=0.35). The %∆ in NIHSS from admittance to discharge was found to be significantly correlated to both systemic (p=0.013; r = -0.409) and intracranial (p=0.011; r = -0.421) VCAM1 levels indicating elevated levels of systemic and intracranial VCAM1 are associated with reduced improvement of stroke severity based on NIHSS from admittance to discharge. STRING-generated analyses identified biologic functional descriptions as well as function-associated proteins from the predictive models of infarct and edema volume.ConclusionsThe current study provides novel data on systemic and intracranial VCAM1 in relation to stroke comorbidities, stroke severity, functional outcomes, and the role VCAM1 plays in complex protein-protein signaling pathways. These data will allow future studies to develop predictive biomarkers and proteomic targets for drug development to improve our ability to treat a devastating pathology.

Project description:Background and purposeThe frequency and clinical significance of the susceptibility vessel sign in patients with acute ischemic stroke remains unclear. We aimed to assess its prevalence in patients with acute ischemic stroke undergoing mechanical thrombectomy and to analyze its association with interventional and clinical outcome parameters in that group.Materials and methodsSix hundred seventy-six patients with acute ischemic stroke and admission MR imaging were reviewed retrospectively. Of those, 577 met the eligibility criteria for further analysis. Imaging was performed using a 1.5T or 3T MR imaging scanner. Associations between baseline variables, interventional and clinical outcome parameters, and susceptibility vessel sign were determined with multivariable logistic regression models. Results are shown as adjusted ORs with 95% CIs.ResultsThe susceptibility vessel sign was present in 87.5% (n = 505) of patients and associated with tandem occlusion (adjusted OR, 3.3; 95% CI, 1.1-10.0; P = .032) as well as successful reperfusion, defined as an expanded TICI score of ≥2b (adjusted OR, 2.4; 95% CI, 1.28-4.6; P = .007). The susceptibility vessel sign was independently associated with functional independence (mRS ≤ 2: adjusted OR, 2.1; 95% CI, 1.1-4.0; P = .028) and lower mortality (adjusted OR, 0.4; 95% CI, 0.2-0.7; P = .003) at 90 days, even after adjusting for successful reperfusion. The susceptibility vessel sign did not influence the number of passes performed during mechanical thrombectomy, the first-pass reperfusion, or the risk of peri- or postinterventional complications.ConclusionsThe susceptibility vessel sign is an MR imaging phenomenon frequently observed in patients with acute ischemic stroke and is associated with successful reperfusion after mechanical thrombectomy. However, superior clinical functional outcome and lower mortality noted in patients showing the susceptibility vessel sign could not be entirely attributed to higher reperfusion rates.

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AutoML accurately predicts endovascular mechanical thrombectomy in acute large vessel ischemic stroke

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