{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:22:15Z","timestamp":1792178535330,"version":"4.4.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T00:00:00Z","timestamp":1689984000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T00:00:00Z","timestamp":1689984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS057676"],"award-info":[{"award-number":["R01NS057676"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal hydrolase (UCH-L1) have been FDA-approved for clinical use in mild and moderate traumatic brain injury (TBI). Understanding sex differences in their diagnostic accuracy over time will help inform clinical practice. We sought to evaluate the sex differences in the temporal profile of GFAP and UCH-L1 in a large cohort of trauma patients presenting to the emergency department. To compare the biomarkers\u2019 diagnostic accuracy in male versus female patients for detecting mild TBI (MTBI), and traumatic intracranial lesions on head CT. This prospective cohort study enrolled female and male adult trauma patients presenting to a Level 1 Trauma Center. All patients underwent rigorous screening to determine whether or not they had experienced a MTBI. Of 3025 trauma patients assessed, 1030 met eligibility criteria and 446 declined. Initial blood samples were obtained in 584 patients enrolled within 4\u00a0h of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180-h post-injury. The main outcomes included the diagnostic accuracy in detection of MTBI and traumatic intracranial lesions on head CT scan. A total of 1831 samples were drawn in 584 patients over 7\u00a0days, 362 (62%) were male and 222 (38%) were female. The pattern of elevation was similar in both sexes. Although the pattern of elevation was similar between male and female for both biomarkers, male patients had significantly higher concentrations of UCH-L1 compared to female patients at several timepoints post-injury, particularly within 24\u00a0h of injury. There were no significant differences in diagnostic accuracy for detecting MTBI or for detecting CT lesions between male and female patients at any timepoint for both GFAP and UCH-L1. Although patterns of GFAP and UCH-L1 release in trauma patients over a week post-injury was similar between the sexes, there were significantly higher concentrations of UCH-L1 in males at several timepoints post-injury. Despite this, the overall diagnostic accuracies of both GFAP and UCH-L1 over time for detecting MTBI and CT lesions were not significantly different between male and female trauma patients.<\/jats:p>","DOI":"10.1038\/s41598-023-38804-4","type":"journal-article","created":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T10:01:34Z","timestamp":1690020094000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Sex differences in time course and diagnostic accuracy of GFAP and UCH-L1 in trauma patients with mild traumatic brain injury"],"prefix":"10.1038","volume":"13","author":[{"given":"Linda","family":"Papa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gretchen M.","family":"Brophy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilmer","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hirschl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marshall","family":"Cress","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Giordano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,22]]},"reference":[{"key":"38804_CR1","unstructured":"FDA authorizes marketing of first blood test to aid in the evaluation of concussion in adults. US Food & Drug Administration. Accessed July 2, 2018."},{"issue":"6","key":"38804_CR2","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.annemergmed.2011.08.021","volume":"59","author":"L Papa","year":"2012","unstructured":"Papa, L. et al. Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention. Ann. Emerg. Med. 59(6), 471\u2013483. https:\/\/doi.org\/10.1016\/j.annemergmed.2011.08.021 (2012).","journal-title":"Ann. Emerg. Med."},{"issue":"5","key":"38804_CR3","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1097\/TA.0b013e3182491e3d","volume":"72","author":"L Papa","year":"2012","unstructured":"Papa, L. et al. Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention. J. Trauma Acute Care Surg. 72(5), 1335\u20131344. https:\/\/doi.org\/10.1097\/TA.0b013e3182491e3d (2012).","journal-title":"J. Trauma Acute Care Surg."},{"issue":"22","key":"38804_CR4","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1089\/neu.2013.3245","volume":"31","author":"L Papa","year":"2014","unstructured":"Papa, L. et al. GFAP out-performs S100beta in detecting traumatic intracranial lesions on computed tomography in trauma patients with mild traumatic brain injury and those with extracranial lesions. J. Neurotrauma 31(22), 1815\u20131822. https:\/\/doi.org\/10.1089\/neu.2013.3245 (2014).","journal-title":"J. Neurotrauma"},{"issue":"5","key":"38804_CR5","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1001\/jamaneurol.2016.0039","volume":"73","author":"L Papa","year":"2016","unstructured":"Papa, L. et al. Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury. JAMA Neurol. 73(5), 551\u2013560. https:\/\/doi.org\/10.1001\/jamaneurol.2016.0039 (2016).","journal-title":"JAMA Neurol."},{"issue":"11","key":"38804_CR6","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1089\/neu.2016.4772","volume":"34","author":"RD Welch","year":"2017","unstructured":"Welch, R. D. et al. Modeling the kinetics of serum glial fibrillary acidic protein, ubiquitin carboxyl-terminal hydrolase-L1, and S100B concentrations in patients with traumatic brain injury. J. Neurotrauma 34(11), 1957\u20131971. https:\/\/doi.org\/10.1089\/neu.2016.4772 (2017).","journal-title":"J. Neurotrauma"},{"issue":"6","key":"38804_CR7","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1111\/acem.13174","volume":"24","author":"LM Lewis","year":"2017","unstructured":"Lewis, L. M. et al. Utility of serum biomarkers in the diagnosis and stratification of mild traumatic brain injury. Acad. Emerg. Med. 24(6), 710\u2013720. https:\/\/doi.org\/10.1111\/acem.13174 (2017).","journal-title":"Acad. Emerg. Med."},{"issue":"9","key":"38804_CR8","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/S1474-4422(18)30231-X","volume":"17","author":"JJ Bazarian","year":"2018","unstructured":"Bazarian, J. J. et al. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): A multicentre observational study. Lancet Neurol. 17(9), 782\u2013789. https:\/\/doi.org\/10.1016\/S1474-4422(18)30231-X (2018).","journal-title":"Lancet Neurol."},{"issue":"1","key":"38804_CR9","doi-asserted-by":"publisher","first-page":"e000473","DOI":"10.1136\/bmjpo-2019-000473","volume":"3","author":"L Papa","year":"2019","unstructured":"Papa, L. et al. Evaluating glial and neuronal blood biomarkers GFAP and UCH-L1 as gradients of brain injury in concussive, subconcussive and non-concussive trauma: A prospective cohort study. BMJ Paediatr. Open 3(1), e000473. https:\/\/doi.org\/10.1136\/bmjpo-2019-000473 (2019).","journal-title":"BMJ Paediatr. Open"},{"issue":"3","key":"38804_CR10","doi-asserted-by":"publisher","first-page":"e221302","DOI":"10.1001\/jamanetworkopen.2022.1302","volume":"5","author":"L Papa","year":"2022","unstructured":"Papa, L. et al. Evaluation of glial and neuronal blood biomarkers compared with clinical decision rules in assessing the need for computed tomography in patients with mild traumatic brain injury. JAMA Netw. Open 5(3), e221302. https:\/\/doi.org\/10.1001\/jamanetworkopen.2022.1302 (2022).","journal-title":"JAMA Netw. Open"},{"issue":"10","key":"38804_CR11","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/S1474-4422(19)30282-0","volume":"18","author":"JK Yue","year":"2019","unstructured":"Yue, J. K. et al. Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: A prospective multicentre study. Lancet Neurol. 18(10), 953\u2013961. https:\/\/doi.org\/10.1016\/S1474-4422(19)30282-0 (2019).","journal-title":"Lancet Neurol."},{"issue":"10\u201311","key":"38804_CR12","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/j.clinbiochem.2014.01.028","volume":"47","author":"FG Strathmann","year":"2014","unstructured":"Strathmann, F. G., Schulte, S., Goerl, K. & Petron, D. J. Blood-based biomarkers for traumatic brain injury: evaluation of research approaches, available methods and potential utility from the clinician and clinical laboratory perspectives. Clin. Biochem. 47(10\u201311), 876\u2013888. https:\/\/doi.org\/10.1016\/j.clinbiochem.2014.01.028 (2014).","journal-title":"Clin. Biochem."},{"key":"38804_CR13","doi-asserted-by":"publisher","first-page":"746491","DOI":"10.3389\/fphar.2021.746491","volume":"12","author":"D Sass","year":"2021","unstructured":"Sass, D. et al. Sex differences in behavioral symptoms and the levels of circulating GFAP, Tau, and NfL in patients with traumatic brain injury. Front. Pharmacol. 12, 746491. https:\/\/doi.org\/10.3389\/fphar.2021.746491 (2021).","journal-title":"Front. Pharmacol."},{"issue":"1","key":"38804_CR14","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1001\/jamapsychiatry.2013.3199","volume":"71","author":"SL Ristvedt","year":"2014","unstructured":"Ristvedt, S. L. The evolution of gender. JAMA Psychiat. 71(1), 13\u201314. https:\/\/doi.org\/10.1001\/jamapsychiatry.2013.3199 (2014).","journal-title":"JAMA Psychiat."},{"issue":"1","key":"38804_CR15","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1148\/radiology.143.1.7063747","volume":"143","author":"JA Hanley","year":"1982","unstructured":"Hanley, J. A. & McNeil, B. J. The meaning and use of the area under a receiver operating characteristic (ROC) curve. 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Cells https:\/\/doi.org\/10.3390\/cells10092265 (2021).","journal-title":"Cells"},{"issue":"2","key":"38804_CR18","doi-asserted-by":"publisher","first-page":"e0191806","DOI":"10.1371\/journal.pone.0191806","volume":"13","author":"D Toliczenko-Bernatowicz","year":"2018","unstructured":"Toliczenko-Bernatowicz, D. et al. Overexpression of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) in boys with cryptorchidism. PLoS One 13(2), e0191806. https:\/\/doi.org\/10.1371\/journal.pone.0191806 (2018).","journal-title":"PLoS One"},{"issue":"23","key":"38804_CR19","doi-asserted-by":"publisher","first-page":"E2123","DOI":"10.1212\/WNL.0000000000006616","volume":"91","author":"BM Asken","year":"2018","unstructured":"Asken, B. M. et al. Concussion BASICS II Baseline serum biomarkers, head impact exposure, and clinical measures. Neurology 91(23), E2123\u2013E2132. https:\/\/doi.org\/10.1212\/WNL.0000000000006616 (2018).","journal-title":"Neurology"},{"issue":"1","key":"38804_CR20","doi-asserted-by":"publisher","first-page":"12230","DOI":"10.1038\/s41598-022-16447-1","volume":"12","author":"JO Harrell","year":"2022","unstructured":"Harrell, J. O. et al. Ubiquitin carboxyl-terminal esterase L1 is not elevated in the serum of concussed rugby players: an observational cross-sectional study. Sci. Rep. 12(1), 12230. https:\/\/doi.org\/10.1038\/s41598-022-16447-1 (2022).","journal-title":"Sci. Rep."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-38804-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-38804-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-38804-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T10:06:56Z","timestamp":1690020416000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-38804-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,22]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["38804"],"URL":"https:\/\/doi.org\/10.1038\/s41598-023-38804-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,22]]},"assertion":[{"value":"16 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11833"}}