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  • 1
    In: Annals of Neurology, Wiley, Vol. 91, No. 5 ( 2022-05), p. 629-639
    Abstract: The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity. Methods In a pooled, patient‐level analysis of 3 randomized controlled trials (EXTEND‐IA, EXTEND‐and IA‐TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90‐day functional independence (modified Rankin Scale [mRS] = 0–2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity. Results We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8–19) in EVT versus 10 (6–15) in MM, p   〈  0.001. Pretreatment ischemic core did not differ (EVT = 10 [0–24] ml vs MM = 9 [3–21] ml, p  = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI]  = 1.25–4.67, p  = 0.008, inverse probability of treatment weights [IPTW]‐OR = 1.75, 95% CI = 1.00–3.75, p  = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23–3.29, p  = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12–0.87, p  = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09–4.79, p  = 0.029, IPTW‐OR = 2.02, 1.08–3.78, p  = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p  = 0.17, IPTW‐OR: 0.71, 95% CI = 0.18–2.78, p  = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds. Interpretation In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022;91:629–639
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2037912-2
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  • 2
    In: Annals of Neurology, Wiley, Vol. 93, No. 4 ( 2023-04), p. 793-804
    Abstract: Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship. Methods In a pooled, patient‐level analysis of the EXTEND‐IA trials and SELECT study, we used a mediation analysis framework to quantify infarct growth and cerebral edema (midline shift) mediation effect on successful reperfusion (modified Treatment in Cerebral Ischemia ≥ 2b) association with functional outcome (modified Rankin Scale distribution). Furthermore, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift. Results A total 542 of 665 (81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful versus unsuccessful reperfusion. Median infarct growth was 12.3ml (interquartile range [IQR] = 1.8–48.4), and median midline shift was 0mm (IQR = 0–2.2). Of 249 (37%) demonstrating a midline shift of ≥1mm, median shift was 2.75mm (IQR = 1.89–4.21). Successful reperfusion was associated with reductions in both predefined mediators, infarct growth (β = −1.19, 95% confidence interval [CI] = −1.51 to −0.88, p   〈  0.001) and midline shift (adjusted odds ratio = 0.36, 95% CI = 0.23–0.57, p   〈  0.001). Successful reperfusion association with improved functional outcome (adjusted common odds ratio [acOR] = 2.68, 95% CI = 1.86–3.88, p   〈  0.001) became insignificant (acOR = 1.39, 95% CI = 0.95–2.04, p  = 0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect, respectively. Analysis considering an alternative hypothesis demonstrated consistent results. Interpretation In this mediation analysis from a pooled, patient‐level cohort, a significant proportion (~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect, and identify novel therapeutic targets to further enhance reperfusion benefits. ANN NEUROL 2023;93:793–804
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2037912-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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