• Endre Czeiter, Krisztina Amrein, Benjamin Y Gravesteijn, Fiona Lecky, David K Menon, Stefania Mondello, Newcombe Virginia F J VFJ Division of Anaesthesia, University of Cambridge, Box 93, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK., Sophie Richter, Ewout W Steyerberg, Vyvere Thijs Vande TV Research and Development, Icometrix, Kolonel Begaultlaan 1b/12, 3012 Leuven, Belgium; Department of Radiology, Antwerp University Hospital and Unive, Jan Verheyden, Haiyan Xu, Zhihui Yang, Maas Andrew I R AIR Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Wijlrijkstraat 10, 2650 Edegem, Belgium., Wang Kevin K W KKW Program for Neurotrauma, Neuroproteomics and Biomarker Research, Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida,, András Büki, and CENTER-TBI Participants and Investigators.
• Department of Neurosurgery, Medical School, University of Pécs, Rét u. 2, H-7623 Pécs, Hungary; Neurotrauma Research Group, Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary; MTA-PTE Clinical Neuroscience MR Research Group, Rét u. 2, H-7623 Pécs, Hungary. Electronic address: endre.czeiter@gmail.com.
• EBioMedicine. 2020 Jun 1; 56: 102785.

BackgroundSerum biomarkers may inform and improve care in traumatic brain injury (TBI). We aimed to correlate serum biomarkers with clinical severity, care path and imaging abnormalities in TBI, and explore their incremental value over clinical characteristics in predicting computed tomographic (CT) abnormalities.MethodsWe analyzed six serum biomarkers (S100B, NSE, GFAP, UCH-L1, NFL and t-tau) obtained <24 h post-injury from 2867 patients with any severity of TBI in the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) Core Study, a prospective, multicenter, cohort study. Univariable and multivariable logistic regression analyses were performed. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals.FindingsAll biomarkers scaled with clinical severity and care path (ER only, ward admission, or ICU), and with presence of CT abnormalities. GFAP achieved the highest discrimination for predicting CT abnormalities (AUC 0•89 [95%CI: 0•87-0•90]), with a 99% likelihood of better discriminating CT-positive patients than clinical characteristics used in contemporary decision rules. In patients with mild TBI, GFAP also showed incremental diagnostic value: discrimination increased from 0•84 [95%CI: 0•83-0•86] to 0•89 [95%CI: 0•87-0•90] when GFAP was included. Results were consistent across strata, and injury severity. Combinations of biomarkers did not improve discrimination compared to GFAP alone.InterpretationCurrently available biomarkers reflect injury severity, and serum GFAP, measured within 24 h after injury, outperforms clinical characteristics in predicting CT abnormalities. Our results support the further development of serum GFAP assays towards implementation in clinical practice, for which robust clinical assay platforms are required.FundingCENTER-TBI study was supported by the European Union 7th Framework program (EC grant 602150).Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

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