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Blood-based biomarkers may facilitate detection of neurocognitive impairment, quantify structural brain injury, and improve prognostication. This study evaluated the potential diagnostic role of validated brain injury biomarkers compared with routine diagnostics in critically ill patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a single-center post hoc analysis of a prospective observational sepsis study conducted in two perioperative ICUs. Critically ill patients with and without sepsis were included. Delirium was assessed using validated tools and structural brain injury was evaluated from radiology reports. Biomarkers\u2014neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP) and Tau\u2014were measured at two time points (enrollment and day 7). Neurological outcome was assessed using the modified Rankin Scale (mRS). 90-day mortality was recorded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>90 patients were analyzed (60 with, 30 without sepsis). Delirium occurred in 54.4% and structural brain injury in 42.2%. At ICU discharge, 23.3% had favorable neurological outcomes. NfL levels were higher in septic patients with delirium (p\u2009=\u20090.038). GFAP was significantly elevated in patients with structural brain injury (p\u2009&lt;\u20090.001). All biomarkers showed prognostic potential; GFAP demonstrated the strongest association with unfavorable outcome (aOR 5.11, 95% CI 1.57\u201322.33). GFAP and UCH-L1 improved AUC in reference model 1 (age\u2009+\u2009SOFA), while all four biomarkers improved AUC in models 2 (age\u2009+\u2009GCS) and 3 (APACHE-II) for predicting poor outcome and 90-day mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Brain injury biomarkers correlate with delirium and structural injury and may enhance outcome prediction in heterogeneous critically ill patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov. NCT06749483. Study Registration Date: 23 December 2024.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s15010-026-02790-2","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:30:50Z","timestamp":1776069050000},"page":"1501-1517","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Correlation of brain injury biomarkers with brain dysfunction, brain injury, and outcomes in critically ill patients: a post hoc exploratory analysis"],"prefix":"10.1007","volume":"54","author":[{"given":"M.","family":"R\u00fchlmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Lehmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Panagiotou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Neugebauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kiehntopf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Klawitter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Ehler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"2790_CR1","doi-asserted-by":"publisher","DOI":"10.1056\/evidoa2200234","author":"M Paton","year":"2023","unstructured":"Paton M, Chan S, Tipping CJ, Stratton A, Neto AS, Lane R, et al. 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His department received funding for clinical trials from Roche, Solvamed GmbH and BioAegis Therapeutics. MB received honoraria for lectures and consulting fees from Artcline GmbH, BRAHMS (ThermoFisher), Bayer AG, Volition, Hillrom Iberia (Baxter), DiaSorin Deutschland GmbH and Deepull Diagnostics. MB is co-owner of several patents (WO 2017041782 A1, WO 2015035974 A1, DE 102006027842 A1, WO 2012013247 A1, WO 2011080184 A1), co-applicant for a pending patent on biomarkers for the prognosis of CAP, and shareholder in SmartDyeLivery GmbH. JE received travel support for attending study meetings by B. Braun Melsungen AG and Novartis, has leadership as second spokesperson of the Scientific Working Group on Neuroanesthesia (WAKNA) of the German Society for Anaesthesiology and Intensive Care Medicine (DGAI) and is Research Committee Member of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC). All other authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The original trial whose dataset was analyzed was approved by the local ethics board of the Friedrich-Schiller University Jena (Ethics identifier: 2019-1306 and 2024-3429-BO) and was registered (ClinicalTrials.gov: NCT06749483). Written informed consent was given by patient or legal representative before study inclusion. No ethics approval was necessary for this secondary post hoc analysis.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}