{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:31:08Z","timestamp":1789047068472,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":["Brain and Behavior"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Systemic endothelial dysfunction is a critical driver of poor outcomes in ischemic stroke. We evaluated the prognostic value of the endothelial activation and stress index (EASIX) in critically ill stroke patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 3063 patients with ischemic stroke from the MIMIC\u2010IV database. The natural log\u2010transformed EASIX (lnEASIX) was calculated from admission LDH, creatinine, and platelets. The primary outcome was designated as 28\u2010day mortality, with secondary outcomes including in\u2010hospital, 90\u2010day, and 180\u2010day mortality. Multivariable logistic and Cox proportional hazards regression, restricted cubic splines (RCS), and advanced clinical utility analyses (NRI, IDI, and decision curve analysis) were utilized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Evaluated as a continuous variable, a per\u2010unit increase in lnEASIX was independently associated with an elevated risk for the primary endpoint of 28\u2010day mortality (OR 1.47, 95% CI 1.36\u20131.59,\n                      <jats:italic>p\u00a0&lt;\u00a0<\/jats:italic>\n                      0.001), as well as all secondary mortality endpoints. RCS analysis confirmed a strictly linear, monotonic dose\u2013response relationship (\n                      <jats:italic>p<\/jats:italic>\n                      for nonlinearity &gt;\u00a00.05). While lnEASIX demonstrated moderate standalone discrimination (AUC 0.64\u20130.67, comparable to SOFA), integrating it with the baseline SOFA score yielded significant incremental predictive value (NRI 0.208, IDI 0.011; both\n                      <jats:italic>p\u00a0&lt;\u00a0<\/jats:italic>\n                      0.01) and superior net clinical benefit. Subgroup analysis revealed consistent prognostic utility across most strata, though the impact was markedly more pronounced in patients without pre\u2010existing cancer (\n                      <jats:italic>p<\/jats:italic>\n                      for interaction &lt;\u00a00.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LnEASIX is a simple, robust, and continuous predictor of short\u2010 and long\u2010term mortality in critically ill patients with ischemic stroke. Integrating this zero\u2010cost biomarker with established intensive care scoring systems provides significant incremental value for early prognostic risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71708","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T03:32:00Z","timestamp":1787283120000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic Value of the Endothelial Activation and Stress Index (EASIX) in Critically Ill Patients With Ischemic Stroke: A MIMIC\u2010IV Database Analysis"],"prefix":"10.1002","volume":"16","author":[{"given":"Wen","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine Yantai Yuhuangding Hospital  Yantai Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manli","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Neurology Yantai Yuhuangding Hospital, Qingdao University  Yantai Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaofei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Yantai Yuhuangding Hospital, Qingdao University  Yantai Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The Affiliated Brain Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurology Yantai Yuhuangding Hospital, Qingdao University  Yantai Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurology Yantai Yuhuangding Hospital, Qingdao University  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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010025\u201003360\u20103"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1681\/asn.0000000792"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102362"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.121.036806"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.122.039005"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.113059"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.125.052018"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102024\u2010009220"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2021.1940139"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.123.044246"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(25)01917\u20108"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474\u20104422(24)00369\u20107"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281\u2010023\u201000992\u20106"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054\u2010025\u201005668\u20101"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2021.119988"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1983455"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2026.8900"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2025.1634877"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2025.06.054"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.123.033341"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2026.158133"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.70063"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2352\u20103026(17)30108\u20104"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.122.028632"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408\u2010019\u20100247\u2010z"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.120.316711"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569\u2010025\u201001162\u2010x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.125.326981"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102013\u2010306476"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000210063"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(26)00876\u20107"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000214655"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2025.1524262"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2024.1388528"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.125.046136"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf01709751"}],"container-title":["Brain 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