Abstract Background and aims Neutrophil extracellular traps (NETs) contribute to microvascular dysfunction, which may be associated with poor functional outcomes in patients with acute ischemic stroke (AIS) and successful recanalization after endovascular treatment (EVT). We aimed to investigate dynamic changes in NETs biomarkers (Myeloperoxidase-associated DNA complexes MPO-DNA and citrullinated Histone H3 CitH3) pre and post-recanalization and the prognostic significance for non-ambulatory functional outcome. Methods In this prospective multicenter cohort, 114 anterior-circulation AIS patients undergoing EVT with successful recanalization (defined as eTICI 2b-3) underwent serial serum measurements of NETs biomarkers before reperfusion therapy, at 24 hours after EVT and at 7days/discharge. Primary outcome was non-ambulatory functional outcome (mRS 4-6 at 90 days in patients with successful recanalization). Univariate and multivariable logistic regression were used to determine the relationship of non-ambulatory functional outcome with NET biomarkers. Results MPO-DNA levels peaked at 24h post-EVT (median 472.29 IQR 386.35-571.09), significantly increased from baseline (341.34 280.72-442.81; P0.001) and declined by 7 days/discharge (327.74 268.17-397.99; P0.001). CitH3 showed a non-significant increase at 24h (14.022 9.322-25.783 vs baseline 12.107 8.810-21.327; P=0.164), followed by a significant decrease at 7 days (11.302 2.824-21.540; P=0.011). NET clearance kinetics (Elevated CitH3 7 days/24 hours ratio) was independently associated with non-ambulatory functional outcome after multivariable adjustment (aOR 1.48, 95% CI 1.04-2.10, P=0.03) with age, baseline National Institutes of Health Stroke Scale (NIHSS), ischemic core volume, MPO-DNA 7 days/24h ratio, and hemoglobin A1c (HbA1c) 6.0%, as covariates. Conclusions NETs clearance deficiency during 24 hours to 7 days is independently associated with post-EVT non-ambulatory functional outcome. Conflict of interest All authors have nothing to disclose.
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Yige Zhang
Sichuan University
Liyuan Wang
Beijing Tian Tan Hospital
G G Li
Beijing Tian Tan Hospital
European Stroke Journal
The Royal Melbourne Hospital
Beijing Tian Tan Hospital
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synapsesocial.com/papers/69fd7fcdbfa21ec5bbf086e9 — DOI: https://doi.org/10.1093/esj/aakag023.533