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Pei-Ya Chen,1,2 Guei-Chiuan Chen,1,2 Cheng-Lun Hsiao,1 Po-Jen Hsu,1 Fu-Yi Yang,1 Chih-Yang Liu,1 Adam Tsou,1 Wan-Ling Chang,1 Hsiu-Hsun Liu,1 Shinn-Kuang Lin1,2 1Stroke Center and Department of Neurology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 2School of Medicine, Tzu Chi University, Hualien, TaiwanCorrespondence: Shinn-Kuang Lin, Tel +886-2-66289779 ext 3129, Fax +886-2-66289009, Email stuartlin0428@gmail.com; sk2022@tzuchi.com.twPurpose: We investigated the differences of clinical features, four immune-inflammatory markers, namely neutrophil counts, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII), as well as outcomes between patients with in-hospital ischemic stroke (IHIS) and out-of-hospital ischemic stroke (OHIS).Patients and Methods: We retrospectively enrolled 72 patients with IHIS and 3330 patients with OHIS.Results: IHIS accounted for 2% of all patients with ischemic stroke and occurred more often in cardiology and orthopedic surgery wards. Infection, cardiac disease, and pulmonary disorder were the most common causes of hospitalization. Compared with those with OHIS, patients with IHIS had higher levels of immune-inflammatory markers, initial National Institute of Health Stroke Scale (NIHSS) scores, longer hospital stays, higher rates of heart disease, large-artery atherosclerosis or cardioembolism, received more intravenous thrombolysis (IVT) or endovascular thrombectomies (EVTs), more complications, unfavorable outcomes, and mortality. Every immune-inflammatory marker exhibited positive correlations with initial NIHSS scores and discharge modified Rankin Scale scores among patients with OHIS. NLR and SII were higher among patients with a fatal outcome in both groups. Among patients receiving IVT, most of treatment time intervals were shorter for those with IHIS than those with OHIS. Significant factors for mortality were NLR > 5.5, atrial fibrillation, and complications, with a C-statistic of 0.897 in those with IHIS; in those with OHIS, these factors were an initial NIHSS score of > 10, NLR > 6.0, atrial fibrillation, prior stroke, cancer history, and complications with a C-statistic of 0.902. The results were similar after replacing the NLR with SII.Conclusion: Patients with IHIS had more complicated clinical features, higher levels of immune-inflammatory markers, and higher rates of mortality than patients with OHIS. The most significant predictor for mortality among those with OHIS was NIHSS score > 10, and the predictors among patients with IHIS were NLR > 5.5 and SII > 2120.Keywords: immune-inflammatory markers, in-hospital ischemic stroke, intrahospital delay, neutrophil-to-lymphocyte ratio, out-of-hospital ischemic stroke, systemic immune-inflammation index