{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:17:22Z","timestamp":1791605842215,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The optimal treatment for distal medium vessel occlusion (DMVO) stroke remains uncertain, and evidence comparing endovascular therapy (EVT) with medical management (MM) is limited. We aimed to develop and validate a predictive modeling tool to assess individual treatment benefit in DMVO stroke using explainable counterfactual treatment estimation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adults with isolated DMVO stroke (M3\u2013M4, A2\u2013A3, or P1\u2013P2) were retrospectively identified from 7 stroke centers. To estimate individualized probabilities of favorable outcome (modified Rankin Scale [mRS]\u2009=\u20090\u20132 at 90\u2009days), we developed a Penalized Logistic Regression (Elastic Net) model. This framework was selected a priori over other explored machine learning algorithms (Decision Tree, Support Vector Classifier, and XGBoost) for its superior interpretability and ability to handle multicollinearity among interaction terms. Inverse Probability of Treatment Weighting (IPTW) was implemented to address confounding by indication in the observational data. Internal validation used repeated K\u2010fold cross\u2010validation and bootstrapping; external validation was performed on an independent cohort (n\u2009=\u200986).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 321 eligible patients, 179 received EVT (55.8%) and 142 received MM (44.2%). Adjusted models showed no significant overall group differences in favorable outcome (adjusted OR [aOR]\u2009=\u20091.32, 95% confidence interval [CI]\u2009=\u20090.97\u20131.80), mortality (aOR\u2009=\u20091.20, 95% CI\u2009=\u20090.78\u20131.85), or symptomatic hemorrhage (aOR\u2009=\u20090.57, 95% CI\u2009=\u20090.21\u20131.58). However, the model identified significant treatment effect heterogeneity; EVT benefit was amplified in patients with higher National Institutes of Health Stroke Scale (NIHSS) and attenuated with increasing treatment delay. Internal validation demonstrated strong performance (area under the receiver operating characteristic curve [AUC]\u2009=\u20090.77, 95% CI\u2009=\u20090.71\u20130.82). External validation confirmed generalizability (AUC\u2009=\u20090.74, 95% CI\u2009=\u20090.63\u20130.84). Individualized treatment estimates showed high concordance with a benchmark causal T\u2010Learner model (Pearson\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.97 internal and\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.98 external).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Although aggregate outcomes did not differ significantly, the validated Distal and Medium Vessel Occlusion Stroke (DUSK) Tool enables individualized estimation of EVT benefit in DMVO stroke. This explainable counterfactual treatment estimation framework supports precision decision making by identifying specific patient subgroups most likely to benefit from EVT over MM. ANN NEUROL 2026;99:1198\u20131209<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78168","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:10:18Z","timestamp":1769598618000},"page":"1198-1209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Individualized Treatment in Distal and Medium Vessel Occlusion Stroke Using a Validated Explainable Counterfactual Treatment Estimation Model"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8279-5078","authenticated-orcid":false,"given":"Mohamed F.","family":"Doheim","sequence":"first","affiliation":[{"name":"Departments of Neurology and Neurosurgery University of Pittsburgh Medical Center  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7393-9989","authenticated-orcid":false,"given":"Mahmoud H.","family":"Mohammaden","sequence":"additional","affiliation":[{"name":"Department of Neurology Emory University School of Medicine  Atlanta GA USA"},{"name":"Marcus Stroke and Neuroscience Center Grady Memorial Hospital  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hend","family":"Abdelhamid","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital Universitario Vall d'Hebron  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Olive\u2010Gadea","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital Universitario Vall d'Hebron  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Rodrigo\u2010Gisbert","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital Universitario Vall d'Hebron  Barcelona 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