TY - JOUR
T1 - Clinical descriptors of disease trajectories in patients with traumatic brain injury in the intensive care unit (CENTER-TBI)
T2 - a multicentre observational cohort study
AU - Åkerlund, Cecilia
AU - Holst, Anders
AU - Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Investigators and Participants
AU - Bhattacharyay, Shubhayu
AU - Stocchetti, Nino
AU - Steyerberg, Ewout
AU - Smielewski, Peter
AU - Menon, David K.
AU - Ercole, Ari
AU - Nelson, David W.
AU - Åkerlund, 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 - Foks, Kelly
AU - Gravesteijn, Benjamin
AU - Haagsma, Juanita A.
AU - Huijben, Jilske
AU - Kompanje, Erwin
AU - Lingsma, Hester
AU - Mikolic, Ana
AU - Nieboer, Daan
AU - Pisica, Dana
AU - Polinder, Suzanne
AU - Retel Helmrich, Isabel
AU - Sewalt, Charlie
AU - Singh, Ranjit D.
AU - Steyerberg, Ewout
AU - Tibboel, Dick
AU - Timmers, Marjolein
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 Elsevier Ltd
PY - 2024/1
Y1 - 2024/1
N2 - Background: Patients with traumatic brain injury are a heterogeneous population, and the most severely injured individuals are often treated in an intensive care unit (ICU). The primary injury at impact, and the harmful secondary events that can occur during the first week of the ICU stay, will affect outcome in this vulnerable group of patients. We aimed to identify clinical variables that might distinguish disease trajectories among patients with traumatic brain injury admitted to the ICU. Methods: We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. We included patients aged 18 years or older with traumatic brain injury who were admitted to the ICU at one of the 65 CENTER-TBI participating centres, which range from large academic hospitals to small rural hospitals. For every patient, we obtained pre-injury data and injury features, clinical characteristics on admission, demographics, physiological parameters, laboratory features, brain biomarkers (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1], S100 calcium-binding protein B [S100B], tau, neurofilament light [NFL], glial fibrillary acidic protein [GFAP], and neuron-specific enolase [NSE]), and information about intracranial pressure lowering treatments during the first 7 days of ICU stay. To identify clinical variables that might distinguish disease trajectories, we applied a novel clustering method to these data, which was based on a mixture of probabilistic graph models with a Markov chain extension. The relation of clusters to the extended Glasgow Outcome Scale (GOS-E) was investigated. Findings: Between Dec 19, 2014, and Dec 17, 2017, 4509 patients with traumatic brain injury were recruited into the CENTER-TBI core dataset, of whom 1728 were eligible for this analysis. Glucose variation (defined as the difference between daily maximum and minimum glucose concentrations) and brain biomarkers (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were consistently found to be the main clinical descriptors of disease trajectories (ie, the leading variables contributing to the distinguishing clusters) in patients with traumatic brain injury in the ICU. The disease trajectory cluster to which a patient was assigned in a model was analysed as a predictor together with variables from the IMPACT model, and prediction of both mortality and unfavourable outcome (dichotomised GOS-E ≤4) was improved. Interpretation: First-day ICU admission data are not the only clinical descriptors of disease trajectories in patients with traumatic brain injury. By analysing temporal variables in our study, variation of glucose was identified as the most important clinical descriptor that might distinguish disease trajectories in the ICU, which should direct further research. Biomarkers of brain injury (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were also top clinical descriptors over time, suggesting they might be important in future clinical practice. Funding: European Union 7th Framework program, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences Corporation, and NeuroTrauma Sciences.
AB - Background: Patients with traumatic brain injury are a heterogeneous population, and the most severely injured individuals are often treated in an intensive care unit (ICU). The primary injury at impact, and the harmful secondary events that can occur during the first week of the ICU stay, will affect outcome in this vulnerable group of patients. We aimed to identify clinical variables that might distinguish disease trajectories among patients with traumatic brain injury admitted to the ICU. Methods: We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. We included patients aged 18 years or older with traumatic brain injury who were admitted to the ICU at one of the 65 CENTER-TBI participating centres, which range from large academic hospitals to small rural hospitals. For every patient, we obtained pre-injury data and injury features, clinical characteristics on admission, demographics, physiological parameters, laboratory features, brain biomarkers (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1], S100 calcium-binding protein B [S100B], tau, neurofilament light [NFL], glial fibrillary acidic protein [GFAP], and neuron-specific enolase [NSE]), and information about intracranial pressure lowering treatments during the first 7 days of ICU stay. To identify clinical variables that might distinguish disease trajectories, we applied a novel clustering method to these data, which was based on a mixture of probabilistic graph models with a Markov chain extension. The relation of clusters to the extended Glasgow Outcome Scale (GOS-E) was investigated. Findings: Between Dec 19, 2014, and Dec 17, 2017, 4509 patients with traumatic brain injury were recruited into the CENTER-TBI core dataset, of whom 1728 were eligible for this analysis. Glucose variation (defined as the difference between daily maximum and minimum glucose concentrations) and brain biomarkers (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were consistently found to be the main clinical descriptors of disease trajectories (ie, the leading variables contributing to the distinguishing clusters) in patients with traumatic brain injury in the ICU. The disease trajectory cluster to which a patient was assigned in a model was analysed as a predictor together with variables from the IMPACT model, and prediction of both mortality and unfavourable outcome (dichotomised GOS-E ≤4) was improved. Interpretation: First-day ICU admission data are not the only clinical descriptors of disease trajectories in patients with traumatic brain injury. By analysing temporal variables in our study, variation of glucose was identified as the most important clinical descriptor that might distinguish disease trajectories in the ICU, which should direct further research. Biomarkers of brain injury (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were also top clinical descriptors over time, suggesting they might be important in future clinical practice. Funding: European Union 7th Framework program, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences Corporation, and NeuroTrauma Sciences.
UR - http://www.scopus.com/inward/record.url?scp=85176941494&partnerID=8YFLogxK
U2 - 10.1016/S1474-4422(23)00358-7
DO - 10.1016/S1474-4422(23)00358-7
M3 - Article
C2 - 37977157
AN - SCOPUS:85176941494
SN - 1474-4422
VL - 23
SP - 71
EP - 80
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 1
ER -