• HelmrichIsabel R A RetelIRARCenter for Medical Decision Making, Department of Public Health, Erasmus University Medical Center, Rotterdam, Netherlands., Endre Czeiter, Krisztina Amrein, András Büki, Hester F Lingsma, David K Menon, Stefania Mondello, Ewout W Steyerberg, Nicole von Steinbüchel, WangKevin K WKKWProgram for Neurotrauma, Neuroproteomics and Biomarker Research, Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville, FL, USA; Brain Rehabilitation Research Center, M, Lindsay Wilson, Haiyan Xu, Zhihui Yang, David van Klaveren, MaasAndrew I RAIRDepartment of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium. Electronic address: andrew.maas@uza.be., and CENTER-TBI participants and investigators.
• Center for Medical Decision Making, Department of Public Health, Erasmus University Medical Center, Rotterdam, Netherlands.
• Lancet Neurol. 2022 Sep 1; 21 (9): 792-802.

BackgroundSeveral studies have reported an association between serum biomarker values and functional outcome following traumatic brain injury. We aimed to examine the incremental (added) prognostic value of serum biomarkers over demographic, clinical, and radiological characteristics and over established prognostic models, such as IMPACT and CRASH, for prediction of functional outcome.MethodsWe used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study. We included patients aged 14 years or older who had blood sampling within 24 h of injury, results from a CT scan, and outcome assessment according to the Glasgow Outcome Scale-Extended (GOSE) at 6 months. Amounts in serum of six biomarkers (S100 calcium-binding protein B, neuron-specific enolase, glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1 [UCH-L1], neurofilament protein-light, and total tau) were measured. The incremental prognostic value of these biomarkers was determined separately and in combination. The primary outcome was the GOSE 6 months after injury. Incremental prognostic value, using proportional odds and a dichotomised analysis, was assessed by delta C-statistic and delta R2 between models with and without serum biomarkers, corrected for optimism with a bootstrapping procedure.FindingsSerum biomarker values and 6-month GOSE were available for 2283 of 4509 patients. Higher biomarker levels were associated with worse outcome. Adding biomarkers improved the C-statistic by 0·014 (95% CI 0·009-0·020) and R2 by 4·9% (3·6-6·5) for predicting GOSE compared with demographic, clinical, and radiological characteristics. UCH-L1 had the greatest incremental prognostic value. Adding biomarkers to established prognostic models resulted in a relative increase in R2 of 48-65% for IMPACT and 30-34% for CRASH prognostic models.InterpretationSerum biomarkers have incremental prognostic value for functional outcome after traumatic brain injury. Our findings support integration of biomarkers-particularly UCH-L1-in established prognostic models.FundingEuropean Union's Seventh Framework Programme, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences, and NeuroTrauma Sciences.Copyright © 2022 Elsevier Ltd. All rights reserved.

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