Browsing by Subject "UCH-L1"

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    Association of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortium
    (JAMA Network, 2020-01-03) McCrea, Michael; Broglio, Steven P.; McAllister, Thomas W.; Gill, Jessica; Giza, Christopher C.; Huber, Daniel L.; Harezlak, Jaroslaw; Cameron, Kenneth L.; Houston, Megan N.; McGinty, Gerald; Jackson, Jonathan C.; Guskiewicz, Kevin; Mihalik, Jason; Brooks, M. Alison; Duma, Stephan; Rowson, Steven; Nelson, Lindsay D.; Pasquina, Paul; Meier, Timothy B.; CARE Consortium Investigators; Foroud, Tatiana; Katz, Barry P.; Saykin, Andrew J.; Campbell, Darren E.; Svoboda, Steven J.; Goldman, Joshua; DiFiori, Jon; Psychiatry, School of Medicine
    Importance: There is potential scientific and clinical value in validation of objective biomarkers for sport-related concussion (SRC). Objective: To investigate the association of acute-phase blood biomarker levels with SRC in collegiate athletes. Design, Setting, and Participants: This multicenter, prospective, case-control study was conducted by the National Collegiate Athletic Association (NCAA) and the US Department of Defense Concussion Assessment, Research, and Education (CARE) Consortium from February 20, 2015, to May 31, 2018, at 6 CARE Advanced Research Core sites. A total of 504 collegiate athletes with concussion, contact sport control athletes, and non-contact sport control athletes completed clinical testing and blood collection at preseason baseline, the acute postinjury period, 24 to 48 hours after injury, the point of reporting being asymptomatic, and 7 days after return to play. Data analysis was conducted from March 1 to November 30, 2019. Main Outcomes and Measures: Glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light chain, and tau were quantified using the Quanterix Simoa multiplex assay. Clinical outcome measures included the Sport Concussion Assessment Tool-Third Edition (SCAT-3) symptom evaluation, Standardized Assessment of Concussion, Balance Error Scoring System, and Brief Symptom Inventory 18. Results: A total of 264 athletes with concussion (mean [SD] age, 19.08 [1.24] years; 211 [79.9%] male), 138 contact sport controls (mean [SD] age, 19.03 [1.27] years; 107 [77.5%] male), and 102 non-contact sport controls (mean [SD] age, 19.39 [1.25] years; 82 [80.4%] male) were included in the study. Athletes with concussion had significant elevation in GFAP (mean difference, 0.430 pg/mL; 95% CI, 0.339-0.521 pg/mL; P < .001), UCH-L1 (mean difference, 0.449 pg/mL; 95% CI, 0.167-0.732 pg/mL; P < .001), and tau levels (mean difference, 0.221 pg/mL; 95% CI, 0.046-0.396 pg/mL; P = .004) at the acute postinjury time point compared with preseason baseline. Longitudinally, a significant interaction (group × visit) was found for GFAP (F7,1507.36 = 16.18, P < .001), UCH-L1 (F7,1153.09 = 5.71, P < .001), and tau (F7,1480.55 = 6.81, P < .001); the interaction for neurofilament light chain was not significant (F7,1506.90 = 1.33, P = .23). The area under the curve for the combination of GFAP and UCH-L1 in differentiating athletes with concussion from contact sport controls at the acute postinjury period was 0.71 (95% CI, 0.64-0.78; P < .001); the acute postinjury area under the curve for all 4 biomarkers combined was 0.72 (95% CI, 0.65-0.79; P < .001). Beyond SCAT-3 symptom score, GFAP at the acute postinjury time point was associated with the classification of athletes with concussion from contact controls (β = 12.298; 95% CI, 2.776-54.481; P = .001) and non-contact sport controls (β = 5.438; 95% CI, 1.676-17.645; P = .005). Athletes with concussion with loss of consciousness or posttraumatic amnesia had significantly higher levels of GFAP than athletes with concussion with neither loss of consciousness nor posttraumatic amnesia at the acute postinjury time point (mean difference, 0.583 pg/mL; 95% CI, 0.369-0.797 pg/mL; P < .001). Conclusions and Relevance: The results suggest that blood biomarkers can be used as research tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in SRC.
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    Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients
    (Mary Ann Liebert, 2021) DeKosky, Steven T.; Kochanek, Patrick M.; Valadka, Alex B.; Clark, Robert S. B.; Chou, Sherry H. Y.; Au, Alicia K.; Horvat, Christopher; Jha, Ruchira M.; Mannix, Rebekah; Wisniewski, Stephen R.; Wintermark, Max; Rowell, Susan E.; Welch, Robert D.; Lewis, Lawrence; House, Stacey; Tanzi, Rudolph E.; Smith, Darci R.; Vittor, Amy Y.; Denslow, Nancy D.; Davis, Michael D.; Glushakova, Olena Y.; Hayes, Ronald L.; Pediatrics, School of Medicine
    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus attacks multiple organs of coronavirus disease 2019 (COVID-19) patients, including the brain. There are worldwide descriptions of neurological deficits in COVID-19 patients. Central nervous system (CNS) symptoms can be present early in the course of the disease. As many as 55% of hospitalized COVID-19 patients have been reported to have neurological disturbances three months after infection by SARS-CoV-2. The mutability of the SARS-COV-2 virus and its potential to directly affect the CNS highlight the urgency of developing technology to diagnose, manage, and treat brain injury in COVID-19 patients. The pathobiology of CNS infection by SARS-CoV-2 and the associated neurological sequelae of this infection remain poorly understood. In this review, we outline the rationale for the use of blood biomarkers (BBs) for diagnosis of brain injury in COVID-19 patients, the research needed to incorporate their use into clinical practice, and the improvements in patient management and outcomes that can result. BBs of brain injury could potentially provide tools for detection of brain injury in COVID-19 patients. Elevations of BBs have been reported in cerebrospinal fluid (CSF) and blood of COVID-19 patients. BB proteins have been analyzed in CSF to detect CNS involvement in patients with infectious diseases, including human immunodeficiency virus and tuberculous meningitis. BBs are approved by the U.S. Food and Drug Administration for diagnosis of mild versus moderate traumatic brain injury and have identified brain injury after stroke, cardiac arrest, hypoxia, and epilepsy. BBs, integrated with other diagnostic tools, could enhance understanding of viral mechanisms of brain injury, predict severity of neurological deficits, guide triage of patients and assignment to appropriate medical pathways, and assess efficacy of therapeutic interventions in COVID-19 patients.