Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study
Endre Czeiter,
Krisztina Amrein,
Benjamin Y. Gravesteijn,
Fiona Lecky,
David K. Menon,
Stefania Mondello,
Virginia F.J. Newcombe,
Sophie Richter,
Ewout W. Steyerberg,
Thijs Vande Vyvere,
Jan Verheyden,
Haiyan Xu,
Zhihui Yang,
Andrew I.R. Maas,
Kevin K.W. Wang,
András Büki
Affiliations
Endre Czeiter
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; Corresponding author at: Neurotrauma Research Group, Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary.
Krisztina Amrein
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
Benjamin Y. Gravesteijn
Center for Medical Decision Making, Department of Public Health, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, Netherlands
Fiona Lecky
Centre for Urgent and emergency care REsearch (CURE), Health Services Research Section, School of Health and Related Research (ScHARR), University of Sheffield, S1 4DA, UK; Emergency Department, Salford Royal Hospital, Stott Ln, Salford M6 8HD, UK
David K. Menon
Division of Anaesthesia, University of Cambridge, Box 93, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK
Stefania Mondello
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria n. 1, 98125 Messina, Italy
Virginia F.J. Newcombe
Division of Anaesthesia, University of Cambridge, Box 93, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK
Sophie Richter
Division of Anaesthesia, University of Cambridge, Box 93, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK
Ewout W. Steyerberg
Center for Medical Decision Making, Department of Public Health, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, Netherlands; Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
Thijs Vande Vyvere
Research and Development, Icometrix, Kolonel Begaultlaan 1b/12, 3012 Leuven, Belgium; Department of Radiology, Antwerp University Hospital and University of Antwerp, Wijlrijkstraat 10, 2650 Edegem, Belgium
Jan Verheyden
Research and Development, Icometrix, Kolonel Begaultlaan 1b/12, 3012 Leuven, Belgium
Haiyan Xu
Program for Neurotrauma, Neuroproteomics and Biomarker Research, Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, L4-100L 1149 South Newell Drive, Gainesville, FL 32611, USA
Zhihui Yang
Program for Neurotrauma, Neuroproteomics and Biomarker Research, Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, L4-100L 1149 South Newell Drive, Gainesville, FL 32611, USA
Andrew I.R. Maas
Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Wijlrijkstraat 10, 2650 Edegem, Belgium
Kevin K.W. Wang
Program for Neurotrauma, Neuroproteomics and Biomarker Research, Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, L4-100L 1149 South Newell Drive, Gainesville, FL 32611, USA; Brain Rehabilitation Research Center, Malcom Randall Veterans Affairs Medical Center (VAMC), 1601 SW Archer Rd. Gainesville, FL 32608, USA
András Büki
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
Background: Serum 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. Methods: We 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. Findings: All 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. Interpretation: Currently 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. Funding: CENTER-TBI study was supported by the European Union 7th Framework program (EC grant 602150).
