Association of early blood-based biomarkers and six-month functional outcomes in conventional severity categories of traumatic brain injury: capturing the continuous spectrum of injury.
Wilson, Lindsay; Newcombe, Virginia F J; Whitehouse, Daniel Pet al.
[en] [en] BACKGROUND: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury.
METHODS: Exposure-response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates.
FINDINGS: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13-15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13-15 and positive CT (1.21-2.81), GCS 9-12 (1.16-2.02), GCS 3-8 (1.09-1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51-1.80) percentages of unfavourable outcome were 37-51% in the lowest quintiles of biomarker levels and reached 90-94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83-3.79), the percentages were 2-4% and 19-28% in the lowest and highest biomarker quintiles, respectively.
INTERPRETATION: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity.
FUNDING: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.
Disciplines :
Neurology Anesthesia & intensive care
Author, co-author :
Wilson, Lindsay; Division of Psychology, University of Stirling, Stirling, United Kingdom. Electronic address: l.wilson@stir.ac.uk
Newcombe, Virginia F J; Division of Anaesthesia and PACE, Department of Medicine, University of Cambridge, Cambridge, United Kingdom
Whitehouse, Daniel P; Division of Anaesthesia and PACE, Department of Medicine, University of Cambridge, Cambridge, United Kingdom
Mondello, Stefania; Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
Maas, Andrew I R; Department of Neurosurgery, Antwerp University Hospital, Edegem, Belgium, Department of Translational Neuroscience, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, Belgium
Menon, David K; Division of Anaesthesia and PACE, Department of Medicine, University of Cambridge, Cambridge, United Kingdom
CENTER-TBI participants and investigators
Ledoux, Didier ; Centre Hospitalier Universitaire de Liège - CHU > > Service des soins intensifs généraux
Language :
English
Title :
Association of early blood-based biomarkers and six-month functional outcomes in conventional severity categories of traumatic brain injury: capturing the continuous spectrum of injury.
European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.The authors are grateful for support provided by the European Union 7th Framework program, Hannelore Kohl Stiftung, One Mind, Integra LifeSciences Corporation, Neuro-Trauma Sciences, and the NIHR Rosetrees Trust. The views expressed are those of the author(s) and not necessarily those of the NIHR, Rosetrees Trust or the Department of Health and Social Care.Data were obtained in CENTER-TBI, a large collaborative project with the support of the European Union 7th Framework program (EC grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA) and from Integra LifeSciences Corporation (USA), and NeuroTrauma Sciences (USA). Data for the CENTER-TBI study has been collected through the Quesgen e-CRF (Quesgen Systems Inc, USA), hosted on the INCF platform and extracted via the INCF Neurobot tool (INCF, Sweden). VFJN holds a NIHR Rosetrees Trust Advanced Fellowship, NIHR302544, which is funded in partnership by the NIHR and Rosetrees Trust. DKM reports grants, personal fees, and non-financial support from GlaxoSmithKline outside the submitted work; personal fees from Neurotrauma Sciences, Lantmannen AB, PressuraNeuro, CSL Behring, and Invex Ltd, outside of the submitted work. Dr Maas reports receiving personal fees from NeuroTrauma Sciences, and PressuraNeuro outside the submitted work. VFJN reports a grant with ROCHE Pharmaceuticals outside the submitted work, and personal fees from Integra outside the submitted work. Dr Wilson reports receiving personal fees from Novartis, Neurotrauma Sciences, and Mass General Brigham outside the submitted work. No other disclosures were reported.
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