{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T06:02:28Z","timestamp":1785132148899,"version":"3.55.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"21-22","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:p>\n                    Non-neurological organ dysfunction (NNOD) is a prevalent complication and contributes to poor outcome after traumatic brain injury (TBI). Contributing factors to NNOD may include initial TBI severity, but this relationship has not been rigorously studied. The objectives of this study were to describe the frequency and timing of NNOD after TBI, evaluate the association between NNOD and outcome (mortality and Glasgow Outcome Score-Extended [GOSE] at 6 months post-injury), and examine the relationship between multimodal markers of initial TBI severity and NNOD. We performed a secondary analysis of data from participants in both the ProTECT III clinical trial (progesterone vs. placebo in participants with moderate-to-severe TBI) and the embedded Bio-ProTECT blood biomarker study (\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    = 536 individuals). We reviewed laboratory and clinical data to determine the prevalence of NNOD in renal, hematological, hepatic, cardiovascular, and respiratory systems, based on the sequential organ failure assessment system. TBI severity was assessed using index Glasgow coma scale score (iGCS\u2014first GCS post-primary resuscitation), Rotterdam computed tomography (CT) score, head-region abbreviated injury scale scores, and baseline TBI biomarkers (S100 calcium binding protein B [S100b], glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCHL1], and spectrin breakdown products [SBDP]). NNOD frequencies by organ system were 72% (respiratory), 52% (cardiovascular), 45% (hematological), 8% (renal), and 2% (hepatic). All TBI severity markers were positively correlated (using Spearman coefficients) with the number of systems in dysfunction. To examine effects of NNOD on outcome independent of TBI severity, we used logistic regression and adjusted for age, sex, iGCS, Rotterdam CT score, and biomarker load score (mean biomarker quartile), wherein each additional system of dysfunction resulted in a 1.30\u00d7 higher odds of unfavorable GOSE (95% confidence interval [CI]: [1.01\u20131.67],\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.04). Stratification analyses revealed the relationship between greater NNOD and worse outcome was most pronounced among individuals with more severe Rotterdam CT and lower GCS scores. In conclusion, NNOD occurs frequently after moderate-to-severe TBI, is associated with higher odds of unfavorable GOSE at 6 months, and is positively associated with multimodal biomarkers of baseline TBI severity. This is the first study to demonstrate a relationship between TBI blood biomarker levels and NNOD. Future study is needed to determine mechanisms of NNOD and their relationships to subsequent neurological injury. While TBI research has historically focused on brain-centric measures and outcomes, this study builds on mounting evidence that non-neurological organ systems play an important role in injury response after TBI.\n                  <\/jats:p>","DOI":"10.1177\/08977151251362234","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T16:19:45Z","timestamp":1763396385000},"page":"1936-1947","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Traumatic Brain Injury Severity Measured by Clinical, Radiographical, and Blood Biomarker Measures Is Associated with Non-Neurological Organ Dysfunction: A Secondary Analysis of ProTECT III and Bio-ProTECT"],"prefix":"10.1177","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0976-0383","authenticated-orcid":false,"given":"David J.","family":"Barton","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica K.","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian G.","family":"Gober","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil","family":"Awan","sequence":"additional","affiliation":[{"name":"Department of Statistics, University of Wisconsin, Madison, Wisconsin, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0858-3533","authenticated-orcid":false,"given":"Raj G.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna C.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Frankel","sequence":"additional","affiliation":[{"name":"Marcus Stroke and Neuroscience Center, Grady Memorial Hospital, Atlanta, Georgia, USA."},{"name":"Department of Neurology, Emory University, Atlanta, Georgia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7145-9105","authenticated-orcid":false,"given":"David W.","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Emory University, Atlanta, Georgia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy K.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ccm.0000155911.01844.54"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/000313480807400921"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2010.01.003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/tsaco-2018-000171"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3171\/2018.8.JNS18676"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2019.6577"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2018.5809"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1404304"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005373-197403000-00001"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.aap.2016.09.025"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2022.0479"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc5007"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1998.15.573"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/HTR.0000000000000067"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2014.09.003"},{"key":"e_1_3_3_17_2","unstructured":"Wagner 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Characterizing Acute Infections and Their Associations with Injury Severity Hospital Course and Seizure Risk after Moderate-to-Severe TBI. In: Poster presentation at 2024 Military Health System Research Symposium August 26\u201329 2024. Kissimmee Florida."},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2020.7072"},{"key":"e_1_3_3_19_2","volume-title":"Traumatic Brain Injury: A Roadmap for Accelerating Progress","author":"National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Care Services; Board on Health Sciences Policy; Committee on Accelerating Progress in Traumatic Brain Injury Research and Care","year":"2022","unstructured":"National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Care Services; Board on Health Sciences Policy; Committee on Accelerating Progress in Traumatic Brain Injury Research and Care. 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