{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:26:44Z","timestamp":1787923604891,"version":"build-2784847793"},"reference-count":26,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Endothelial dysfunction is a key component of sepsis pathophysiology. The Endothelial Activation and Stress Index (EASIX) is a practical biomarker derived from routine laboratory parameters and indirectly reflects endothelial injury. This study aimed to evaluate the prognostic association of EASIX with in-hospital mortality and organ-support requirements among patients with pneumosepsis admitted to the intensive care unit (ICU). Methods: This retrospective cohort study included 1787 adult patients with pneumosepsis admitted to a tertiary ICU from January 2018 to December 2025. EASIX was calculated from laboratory parameters obtained at ICU admission, and log2-EASIX was used in all analyses. The primary outcome was in-hospital mortality. Secondary outcomes included the need for invasive mechanical ventilation (IMV), vasopressor therapy within the first 24 h, second-line vasopressor therapy, and continuous renal replacement therapy (CRRT) within the first 7 days after ICU admission. Associations with the primary and secondary outcomes were evaluated using univariable and multivariable logistic regression, and discriminative performance was assessed using receiver operating characteristic (ROC) curve analysis. Results: The in-hospital mortality rate was 56.2%. Log2-EASIX was independently associated with in-hospital mortality (OR: 1.191, 95% CI: 1.119\u20131.268; p &lt; 0.001). ROC analysis showed moderate discrimination for predicting in-hospital mortality (AUC: 0.673, 95% CI: 0.648\u20130.698), with a ROC-derived exploratory cut-off of 1.47. Patients with log2-EASIX \u2265 1.47 had approximately a two-fold higher risk of in-hospital mortality (OR: 2.039, 95% CI: 1.610\u20132.584; p &lt; 0.001). In multivariable analyses of the secondary outcomes, log2-EASIX remained independently associated with second-line vasopressor requirement (adjusted OR: 1.104, 95% CI: 1.040\u20131.171; p = 0.001) and CRRT requirement within 7 days (adjusted OR: 1.317, 95% CI: 1.236\u20131.404; p &lt; 0.001). However, its associations with IMV and initial vasopressor requirements were not statistically significant after adjustment. Adding log2-EASIX to the Acute Physiology and Chronic Health Evaluation (APACHE) II resulted in a statistically significant but small improvement in discrimination compared with APACHE II alone (AUC: 0.761 vs. 0.740; \u0394AUC = 0.021; 95% CI: 0.010\u20130.032; p &lt; 0.001). Conclusions: EASIX was independently associated with in-hospital mortality and second-line vasopressor requirement, and it remained associated with CRRT requirement after multivariable adjustment. However, serum creatinine alone showed superior discrimination for CRRT, suggesting that the association between EASIX and CRRT may be driven, at least in part, by its creatinine component and should therefore be interpreted cautiously. In contrast, the associations of EASIX with early IMV and initial vasopressor requirements were not significant after multivariable adjustment. Although its discriminative performance for mortality was moderate when used alone, EASIX may provide complementary prognostic information when added to established disease severity assessment. These findings warrant validation in prospective, multicenter studies.<\/jats:p>","DOI":"10.3390\/life16091429","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:27:46Z","timestamp":1787920066000},"page":"1429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of the Endothelial Activation and Stress Index (EASIX) with Clinical Outcomes in Patients with Pneumosepsis: A Retrospective Cohort Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Derya","family":"\u00d6zyi\u011fito\u011flu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Sultan 2. Abdulhamid Han Training and Research Hospital, Istanbul 34668, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6485-342X","authenticated-orcid":false,"given":"Ay\u015fe","family":"\u00c7apar","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, Sultan 2. Abdulhamid Han Training and Research Hospital, Istanbul 34668, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1898-5779","authenticated-orcid":false,"given":"Emre","family":"\u00c7apar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Marmara University Pendik Training and Research Hospital, Istanbul 34899, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1495-6508","authenticated-orcid":false,"given":"\u015eeyma","family":"Ba\u015fl\u0131lar","sequence":"additional","affiliation":[{"name":"Department of Chest Diseases, Sultan 2. Abdulhamid Han Training and Research Hospital, Istanbul 34668, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"Jama"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4161\/viru.27372","article-title":"Epidemiology of severe sepsis","volume":"5","author":"Mayr","year":"2014","journal-title":"Virulence"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ceccato, A., and Torres, A. (2018). Sepsis and community-acquired pneumonia. Ann. Res. Hosp., 2.","DOI":"10.21037\/arh.2018.06.01"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kreczko, M.J., Bieniaszewska, M., Steckiewicz, K.P., and Owczuk, R. (2026). Endothelial Activation and Stress Index as an Indicator of Early Hemodynamic Instability in Critically Ill Patients: A Single-Centre Observational Study. Diagnostics, 16.","DOI":"10.3390\/diagnostics16091355"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"R7","DOI":"10.1186\/cc11145","article-title":"Clinical utility of biomarkers of endothelial activation in sepsis-a systematic review","volume":"16","author":"Xing","year":"2012","journal-title":"Crit. Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/SHK.0000000000000473","article-title":"The endothelium in sepsis","volume":"45","author":"Ince","year":"2016","journal-title":"Shock"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.7150\/ijms.85870","article-title":"Association between endothelial activation and stress index and 28-day mortality in septic ICU patients: A retrospective cohort study","volume":"20","author":"Xu","year":"2023","journal-title":"Int. J. Med. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Li, N., Yin, J., Zeng, Y., Li, S., Huang, C., Chen, G., Luo, H., and Jiang, Y. (2025). Association between endothelial activation and stress index and all-cause mortality risk in sepsis patients: A retrospective cohort analysis utilizing the MIMIC-IV database. BMC Infect. Dis., 25.","DOI":"10.1186\/s12879-025-11363-x"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yang, C., Zhou, S., Wen, C., and Chen, J. (2026). The endothelial activation and stress index as a predictor of 28-day mortality in pulmonary sepsis: A retrospective two-cohort analysis. Front. Med., 13.","DOI":"10.3389\/fmed.2026.1714682"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e414","DOI":"10.1016\/S2352-3026(17)30108-4","article-title":"EASIX in patients with acute graft-versus-host disease: A retrospective cohort analysis","volume":"4","author":"Luft","year":"2017","journal-title":"Lancet Haematol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Raia, L., and Zafrani, L. (2022). Endothelial activation and microcirculatory disorders in sepsis. Front. Med., 9.","DOI":"10.3389\/fmed.2022.907992"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1007\/s00134-024-07586-2","article-title":"Understanding, assessing and treating immune, endothelial and haemostasis dysfunctions in bacterial sepsis","volume":"50","author":"Girardis","year":"2024","journal-title":"Intensive Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s00415-026-13941-8","article-title":"The endothelial activation and stress index (EASIX) predicts hazards of short-and long-term mortality in acute ischemic stroke: A retrospective cohort study","volume":"273","author":"Kleeberg","year":"2026","journal-title":"J. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"23285","DOI":"10.1038\/s41598-025-06595-5","article-title":"Endothelial activation and stress index is a reliable predictor for the prevalence and mortality outcomes of stroke","volume":"15","author":"Huang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yang, M., Zhou, Z., Lu, Y., Lin, Y., Miao, S., Yang, Z., Yan, J., and Hu, W. (2026). Prognostic significance of the endothelial activation and stress index in acute respiratory distress syndrome: A retrospective cohort study. Sci. Rep.","DOI":"10.1038\/s41598-026-59327-8"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tang, J., Li, H., Zhang, Z., Cao, J., and Nie, H. (2026). Relationship of the Endothelial Activation and Stress Index with 28-day mortality in urosepsis patients: A retrospective two-cohort investigation. Front. Med., 13.","DOI":"10.3389\/fmed.2026.1761104"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Maneta, E., Aivalioti, E., Tual-Chalot, S., Emini Veseli, B., Gatsiou, A., Stamatelopoulos, K., and Stellos, K. (2023). Endothelial dysfunction and immunothrombosis in sepsis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1144229"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s40635-023-00582-8","article-title":"Capillary leak and endothelial permeability in critically ill patients: A current overview","volume":"11","author":"Saravi","year":"2023","journal-title":"Intensive Care Med. Exp."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/ki.2013.286","article-title":"TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis","volume":"85","author":"Xu","year":"2014","journal-title":"Kidney Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41581-021-00489-1","article-title":"Renal microvascular endothelial cell responses in sepsis-induced acute kidney injury","volume":"18","author":"Molema","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.kint.2016.07.032","article-title":"Renal perfusion in sepsis: From macro-to microcirculation","volume":"91","author":"Post","year":"2017","journal-title":"Kidney Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"117180","DOI":"10.1016\/j.biopha.2024.117180","article-title":"Endothelial dysfunction: Pathophysiology and therapeutic targets for sepsis-induced multiple organ dysfunction syndrome","volume":"178","author":"Tang","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"995","DOI":"10.17305\/bb.2025.13231","article-title":"Endothelial activation and stress index predicts 28-day mortality in patients undergoing CRRT","volume":"26","author":"Hu","year":"2025","journal-title":"Biomol. Biomed."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gokcinar, D., Lafci, A., and Izdes, S. (2025). Endothelial activation and stress index (EASIX) to predict the outcome of patients with COVID-19. COVID, 5.","DOI":"10.3390\/covid5060089"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/9\/1429\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:40:17Z","timestamp":1787920817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/9\/1429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":26,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["life16091429"],"URL":"https:\/\/doi.org\/10.3390\/life16091429","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]}}}