TY - JOUR
T1 - Prognostic Value of a Combination of Circulating Biomarkers in Critically Ill Patients with Traumatic Brain Injury
T2 - Results from the European CREACTIVE Study
AU - Gradisek, Primoz
AU - Carrara, Greta
AU - Antiga, Luca
AU - Bottazzi, Barbara
AU - Chieregato, Arturo
AU - Csomos, Akos
AU - Fainardi, Enrico
AU - Filekovic, Suada
AU - Fleming, Joanne
AU - Hadjisavvas, Andreas
AU - Kaps, Rafael
AU - Kyprianou, Theodoros
AU - Latini, Roberto
AU - Lazar, Isaac
AU - Masson, Serge
AU - Mikaszewska-Sokolewicz, Malgorzata
AU - Novelli, Deborah
AU - Paci, Giulia
AU - Xirouchaki, Nektaria
AU - Zanier, Elisa
AU - Nattino, Giovanni
AU - Bertolini, Guido
N1 - Funding Information:
The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement number 602714.
Publisher Copyright:
© Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Individualized patient care is essential to reduce the global burden of traumatic brain injury (TBI). This pilot study focused on TBI patients admitted to intensive care units (ICUs) and aimed at identifying patterns of circulating biomarkers associated with the disability level at 6 months from injury, measured by the extended Glasgow Outcome Scale (GOS-E). The concentration of 107 biomarkers, including proteins related to inflammation, innate immunity, TBI, and central nervous system, were quantified in blood samples collected on ICU admission from 80 patients. Patients were randomly selected among those prospectively enrolled in the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) observational study. Six biomarkers were selected to be associated with indicators of primary or secondary brain injury: three glial proteins (glial cell-derived neurotrophic factor, glial fibrillary acidic protein, and S100 calcium-binding protein B) and three cytokines (stem cell factor, fibroblast growth factor [FGF] 23 and FGF19). The subjects were grouped into three clusters according to the expression of these proteins. The distribution of the 6-month GOS-E was significantly different across clusters (p < 0.001). In two clusters, the number of 6-month deaths or vegetative states was significantly lower than expected, as calculated according to a customization of the corticosteroid randomization after significant head injury (CRASH) scores (observed/expected [O/E] events = 0.00, 95% confidence interval [CI]: 0.00-0.90 and 0.00, 95% CI: 0.00-0.94). In one cluster, less-than-expected unfavorable outcomes (O/E = 0.50, 95% CI: 0.05-0.95) and more-than-expected good recoveries (O/E = 1.55, 95% CI: 1.05-2.06) were observed. The improved prognostic accuracy of the pattern of these six circulating biomarkers at ICU admission upon established clinical parameters and computed tomography results needs validation in larger, independent cohorts. Nonetheless, the results of this pilot study are promising and will prompt further research in personalized medicine for TBI patients.
AB - Individualized patient care is essential to reduce the global burden of traumatic brain injury (TBI). This pilot study focused on TBI patients admitted to intensive care units (ICUs) and aimed at identifying patterns of circulating biomarkers associated with the disability level at 6 months from injury, measured by the extended Glasgow Outcome Scale (GOS-E). The concentration of 107 biomarkers, including proteins related to inflammation, innate immunity, TBI, and central nervous system, were quantified in blood samples collected on ICU admission from 80 patients. Patients were randomly selected among those prospectively enrolled in the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) observational study. Six biomarkers were selected to be associated with indicators of primary or secondary brain injury: three glial proteins (glial cell-derived neurotrophic factor, glial fibrillary acidic protein, and S100 calcium-binding protein B) and three cytokines (stem cell factor, fibroblast growth factor [FGF] 23 and FGF19). The subjects were grouped into three clusters according to the expression of these proteins. The distribution of the 6-month GOS-E was significantly different across clusters (p < 0.001). In two clusters, the number of 6-month deaths or vegetative states was significantly lower than expected, as calculated according to a customization of the corticosteroid randomization after significant head injury (CRASH) scores (observed/expected [O/E] events = 0.00, 95% confidence interval [CI]: 0.00-0.90 and 0.00, 95% CI: 0.00-0.94). In one cluster, less-than-expected unfavorable outcomes (O/E = 0.50, 95% CI: 0.05-0.95) and more-than-expected good recoveries (O/E = 1.55, 95% CI: 1.05-2.06) were observed. The improved prognostic accuracy of the pattern of these six circulating biomarkers at ICU admission upon established clinical parameters and computed tomography results needs validation in larger, independent cohorts. Nonetheless, the results of this pilot study are promising and will prompt further research in personalized medicine for TBI patients.
KW - Glasgow outcome scale
KW - circulating biomarkers
KW - cluster analysis
KW - traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=85116408874&partnerID=8YFLogxK
U2 - 10.1089/neu.2021.0066
DO - 10.1089/neu.2021.0066
M3 - Article
C2 - 34235978
AN - SCOPUS:85116408874
SN - 0897-7151
VL - 38
SP - 2667
EP - 2676
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 19
ER -