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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

Shinn-Kuang Lin,1,2 Pei-Ya Chen,1,2 Guei-Chiuan Chen,1 Po-Jen Hsu,1 Cheng-Lun Hsiao,1 Fu-Yi Yang,1 Chih-Yang Liu,1 Adam Tsou1 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 LinStroke Center and Department of Neurology, Taipei Tzu Chi Hospital, No. 289, Jian Guo Road, 231, Sindian District, New Taipei City, TaiwanTel +886-2-66289779 ext 3129Fax +886-2-66289009Email stuartlin0428@gmail.comPurpose: Immune–inflammatory processes are involved in all the stages of stroke. This study investigated the association of the neutrophil-to-lymphocyte ratio (NLR) with the hyperdense artery sign (HAS) observed on brain computed tomography (CT) and with clinical features in patients with acute ischemic stroke.Methods: We retrospectively enrolled 2903 inpatients with acute ischemic stroke from May 2010 to May 2019. Data collected included imaging studies, risk factors, laboratory parameters, and clinical features during hospitalization.Results: The HAS was identified in 6% of the 2903 patients and 66% of the 236 patients with acute middle cerebral artery occlusion. Patients with the HAS had a higher NLR. HAS prevalence was higher in men and patients with cardioembolism. The NLR exhibited positive linear correlations with age, glucose and creatinine levels, length of hospital stay, initial National Institutes of Health Stroke Scale (NIHSS) scores, and mRS scores at discharge. The NLR was significantly higher in patients with large-artery atherosclerosis and cardioembolism and was the highest in patients with other determined etiology. Multivariate analysis revealed that an initial NIHSS score of ≥ 10 and an NLR of > 3.5 were significant positive factors, whereas diabetes mellitus and age > 72 years were significant negative factors for the HAS, with a predictive performance of 0.893. An initial NIHSS score of ≥ 5, positive HAS, age > 75 years, diabetes mellitus, an NLR of > 3.5, female sex, a white blood cell count of > 8 × 103/mL, and elevated troponin I were significant predictors of unfavorable outcomes, with a predictive performance of 0.886.Conclusion: An NLR of > 3.5 enabled an efficient prediction of CT HAS. In addition to conventional risk factors and laboratory parameters, both an NLR of > 3.5 and CT HAS enabled improved prediction of unfavorable stroke outcomes.Keywords: acute ischemic stroke, hyperdense artery sign, neutrophil-to-lymphocyte ratio, NIHSS, unfavorable outcome

Background Atherosclerosis is a chronic inflammatory process that occurs in the arterial wall. This immuno-inflammatory process plays a role throughout all stages of stroke. Neutrophils, lymphocytes, and platelets are crucial blood cells for innate and adaptive immunity. This study investigated the associations of four types of immuno-inflammatory markers, namely the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil count (NC), with clinical outcomes in patients with acute ischemic stroke. Methods In this retrospective study, we enrolled 2903 inpatients with acute ischemic stroke from May 2010 to May 2019. Data included risk factors, laboratory parameters, and clinical features during hospitalization. The National Institutes of Health Stroke Scale (NIHSS), and modified Rankin Scale (mRS) were used to assess stroke severity and outcomes. Results All four immuno-inflammatory markers exhibited positive linear correlations with age, glucose, creatinine, length of hospital stay, NIHSS score on admission, and mRS score at discharge. The levels of the four immuno-inflammatory markers were significantly higher in patients with large-artery atherosclerosis and cardioembolism and were highest in patients with other determined etiology. Patients with levels of immuno-inflammatory markers higher than their cutoff values for unfavorable outcomes also exhibited higher rates of cancer history (except for SII and NC), uremia (except for NC), elevated troponin I, and in-hospital complications. Multivariate analysis including SII revealed that admission NIHSS score ≥ 5, age > 75 years, SII > 724, diabetes mellitus, female sex, elevated troponin I, heart disease, and prior stroke were significant predictors for unfavorable outcomes. These significant predictors were retained after replacing SII > 724 with NLR > 143, PLR > 3.5, or NC > 6 × 10 3 /mL, except for prior stroke. For a basic model comprising seven significant predictors of unfavorable outcomes, the C-statistic was 0.860. The addition of SII, NLR, and PLR to the basic model resulted in a significant improvement in the prediction performance to 0.864, 0.863, and 0.863, respectively. Conclusions Immuno-inflammatory markers provide more useful information than conventional risk factors and other laboratory parameters for the prediction of stroke outcomes. SII > 724 is the most appropriate marker when combined with other predictors.