{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:13:22Z","timestamp":1793384002009,"version":"4.5.0"},"reference-count":51,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi240957-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Blood-based biomarkers may clarify underlying neuropathology and potentially assist in clinical management of adolescents with sport-related concussion (SRC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi240957-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the association between SRC and plasma biomarkers in adolescents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi240957-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>Prospective cohort study in Canadian sport and clinic settings (Surveillance in High Schools and Community Sport to Reduce Concussions and Their Consequences study; September 2019 to November 2022). Participants were a convenience sample of 849 adolescent (ages 10-18 years) sport participants with blood samples. Data were analyzed from February to September 2023.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi240957-7\">\n                    <jats:title>Exposures<\/jats:title>\n                    <jats:p>Blood collection and clinical testing preseason (uninjured) and post-SRC follow-ups (ie, \u226472 hours, 1 week, and biweekly until medical clearance to return to play [RTP]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi240957-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Plasma glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase-L1 (UCH-L1), neurofilament light (NfL), and total tau (t-tau) were assayed. Group-level comparisons of biomarker levels were conducted between uninjured and post-SRC intervals (postinjury day [PID] 0-3, 4-10, 11-28, and &amp;amp;gt;28) considering age and sex as modifiers. Secondary analyses explored associations between biomarker concentrations and clinical outcomes (Sport Concussion Assessment Tool, Fifth Edition [SCAT5] symptom scores and time to RTP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi240957-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      This study included 1023 plasma specimens from 695 uninjured participants (467 male participants [67.2%]; median [IQR] age, 15.90 [15.13-16.84] years) and 154 participants with concussion (78 male participants [51.0%]; median [IQR] age, 16.12 [15.31-17.11] years). Acute (PID 0-3) differences relative to uninjured levels were found for GFAP (female participants: 17.8% increase; \u03b2\u2009=\u20090.164; 95% CI, 0.064 to 0.263;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.001; male participants: 17.1% increase; \u03b2\u2009=\u20090.157; 95% CI, 0.086 to 0.229;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001), UCH-L1 (female participants: 43.4% increase; \u03b2\u2009=\u20090.361; 95% CI, 0.125 to 0.596;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.003), NfL (male participants: 19.0% increase; \u03b2\u2009=\u20090.174; 95% CI, 0.087 to 0.261;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001), and t-tau (female participants: \u221222.9%; \u03b2\u2009=\u2009\u22120.260; 95% CI, \u22120.391 to \u22120.130;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001; male participants: \u221218.4%; \u03b2\u2009=\u2009\u22120.203; 95% CI, \u22120.300 to \u22120.106;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001). Differences were observed for all biomarkers at PID 4 to 10, 11 to 28, and greater than 28 compared with uninjured groups. GFAP, NfL, and t-tau were associated with SCAT5 symptom scores across several PID intervals. Higher GFAP after 28 days post-SRC was associated with earlier clearance to RTP (hazard ratio, 4.78; 95% CI, 1.59 to 14.31;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.01). Male participants exhibited lower GFAP (\u22129.7%), but higher UCH-L1 (21.3%) compared with female participants. Age was associated with lower GFAP (\u22125.4% per year) and t-tau (\u22125.3% per year).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi240957-10\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In this cohort study of 849 adolescents, plasma biomarkers differed between uninjured participants and those with concussions, supporting their continued use to understand concussion neuropathology. Age and sex are critical considerations as these biomarkers progress toward clinical validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.31959","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T11:49:03Z","timestamp":1725536943000},"page":"e2431959","source":"Crossref","is-referenced-by-count":28,"title":["Plasma Biomarkers of Traumatic Brain Injury in Adolescents With Sport-Related Concussion"],"prefix":"10.1001","volume":"7","author":[{"given":"Jason B.","family":"Tabor","sequence":"first","affiliation":[{"name":"Sport Injury Prevention Research Centre, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada"},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linden 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas D.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Clinical Neurological Sciences, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Smirl","sequence":"additional","affiliation":[{"name":"Sport Injury Prevention Research Centre, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada"},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Esser","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith Owen","family":"Yeates","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"},{"name":"Department of Psychology, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl L.","family":"Wellington","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantel T.","family":"Debert","sequence":"additional","affiliation":[{"name":"Sport Injury Prevention Research Centre, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada"},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"},{"name":"Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn A.","family":"Emery","sequence":"additional","affiliation":[{"name":"Sport Injury Prevention Research Centre, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada"},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"},{"name":"Departments of Pediatrics and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, 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