TY - JOUR
T1 - Association of early blood-based biomarkers and six-month functional outcomes in conventional severity categories of traumatic brain injury
T2 - capturing the continuous spectrum of injury
AU - Wilson, Lindsay
AU - Newcombe, Virginia F.J.
AU - CENTER-TBI Participants and Investigators
AU - Whitehouse, Daniel P.
AU - Mondello, Stefania
AU - Maas, Andrew I.R.
AU - Menon, David K.
AU - Ackerlund, Cecilia
AU - Amrein, Krisztina
AU - Andelic, Nada
AU - Andreassen, Lasse
AU - Anke, Audny
AU - Antoni, Anna
AU - Audibert, Gérard
AU - Azouvi, Philippe
AU - Azzolini, Maria Luisa
AU - Bartels, Ronald
AU - Barzó, Pál
AU - Beauvais, Romuald
AU - Beer, Ronny
AU - Bellander, Bo Michael
AU - Belli, Antonio
AU - Benali, Habib
AU - Berardino, Maurizio
AU - Beretta, Luigi
AU - Blaabjerg, Morten
AU - Bragge, Peter
AU - Foks, Kelly
AU - Gravesteijn, Benjamin
AU - Haagsma, Juanita A.
AU - Haitsma, Iain
AU - Huijben, Jilske
AU - Kompanje, Erwin
AU - Lingsma, Hester
AU - Mikolic, Ana
AU - Mikolic, Ana
AU - Nieboer, Daan
AU - Pisica, Dana
AU - Polinder, Suzanne
AU - Helmrich, Isabel Retel
AU - Singh, Ranjit D.
AU - Sewalt, Charlie
AU - Steyerberg, Ewout W.
AU - Tibboel, Dick
AU - van der Jagt, Mathieu
AU - van Essen, Thomas A.
AU - van Veen, Ernest
AU - Velt, Kimberley
AU - Volovici, Victor
AU - Voormolen, Daphne
AU - Wiegers, Eveline
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/9
Y1 - 2024/9
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85202203582
U2 - 10.1016/j.ebiom.2024.105298
DO - 10.1016/j.ebiom.2024.105298
M3 - Article
C2 - 39191173
AN - SCOPUS:85202203582
SN - 2352-3964
VL - 107
JO - EBioMedicine
JF - EBioMedicine
M1 - 105298
ER -