Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury (CENTER-TBI): an observational cohort study.

Isabel R A Retel Helmrich, Endre Czeiter, Krisztina Amrein, András Büki, Hester F Lingsma, David K Menon, Stefania Mondello, Ewout W Steyerberg, Nicole von Steinbüchel, Kevin K W Wang, Lindsay Wilson, Haiyan Xu, Zhihui Yang, David van Klaveren, Andrew I R Maas

Journal: The Lancet. Neurology 2022;21(9):792-802

PMID: 35963262

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Several 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.

METHODS

We 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 R between models with and without serum biomarkers, corrected for optimism with a bootstrapping procedure.

FINDINGS

Serum 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 R 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 R of 48-65% for IMPACT and 30-34% for CRASH prognostic models.

INTERPRETATION

Serum 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.

FUNDING

European Union's Seventh Framework Programme, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences, and NeuroTrauma Sciences.

Address: Center for Medical Decision Making, Department of Public Health, Erasmus University Medical Center, Rotterdam, Netherlands.; Department of Neurosurgery, Medical School, and Neurotrauma Research Group, Szentágothai Research Centre, University of Pécs, Pécs, Hungary; MTA-PTE Clinical Neuroscience MR Research Group, Pécs, Hungary.; Department of Neurosurgery, Medical School, and Neurotrauma Research Group, Szentágothai Research Centre, University of Pécs, Pécs, Hungary; Department of Neurosurgery Faculty of Medicine and Health Örebro University, Örebro, Sweden.; Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.; Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.; Center for Medical Decision Making, Department of Public Health, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands.; Institute of Medical Psychology and Medical Sociology, Universitätsmedizin Göttingen, Göttingen, Germany.; Program 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, Malcom Randall Veterans Affairs Medical Center, Gainesville, FL, USA.; Division of Psychology, University of Stirling, Stirling, UK.; Program for Neurotrauma, Neuroproteomics and Biomarker Research, Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville, FL, USA.; Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies/Tufts Medical Center, Boston, MA, USA.; Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium. Electronic address: [email protected].

DOI: 10.1016/S1474-4422(22)00218-6

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MeSH Terms: Biomarkers, Brain Injuries, Traumatic, Cohort Studies, Humans, Prognosis, Prospective Studies, Ubiquitin Thiolesterase