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, L.; Newcombe, V.F.J.; Whitehouse, D.P.; Mondello, S.; Maas, A.I.R.; Menon, D.K.; Ackerlund, C.; Amrein, K.; Andelic, N.; Andreassen, L.; Anke, A.; Antoni, A.; Audibert, G.; Azouvi, P.; Azzolini, M.L.; Bartels, R.; Barzo, P.; Beauvais, R.; Beer, R.; Bellander, B.-.; Belli, A.; Benali, H.; Berardino, M.; Beretta, L.; Blaabjerg, M.; Bragge, P.; Brazinova, A.; Brinck, V.; Brooker, J.; Brorsson, C.; Buki, A.; Bullinger, M.; Cabeleira, M.; Caccioppola, A.; Calappi, E.; Calvi, M.R.; Cameron, P.; Lozano, G.C.; Carbonara, M.; Castano-Leon, A.M.; Cavallo, S.; Chevallard, G.; Chieregato, A.; Citerio, G.; Clusmann, H.; Coburn, M.S.; Coles, J.; Cooper, J.D.; Correia, M.; Covic, A.; Curry, N.; Czeiter, E.; Czosnyka, M.; Dahyot-Fizelier, C.; Dark, P.; Dawes, H.; De Keyser, V.; Degos, V.; Della Corte, F.; Boogert, H.D.; Depreitere, B.; Dilvesi, D.; Dixit, A.; Donoghue, E.; Dreier, J.; Duliere, G.-.; Ercole, A.; Esser, P.; Ezer, E.; Fabricius, M.; Feigin, V.L.; Foks, K.; Frisvold, S.; Furmanov, A.; Gagliardo, P.; Galanaud, D.; Gantner, D.; Gao, G.; George, P.; Ghuysen, A.; Giga, L.; Glocker, B.; Golubovic, J.; Gomez, P.A.; Gratz, J.; Gravesteijn, B.; Grossi, F.; Gruen, R.L.; Gupta, D.; Haagsma, J.A.; Haitsma, I.; Helbok, R.; Helseth, E.; Horton, L.; Huijben, J.; Hutchinson, P.J.; Jacobs, B.; Jankowski, S.; Jarrett, M.; Jiang, J.-.; Johnson, F.; Jones, K.; Karan, M.; Kolias, A.G.; Kompanje, E.; Kondziella, D.; Kornaropoulos, E.; Koskinen, L.-.; Kovacs, N.; Kowark, A.; Lagares, A.; Lanyon, L.; Laureys, S.; Lecky, F.; Ledoux, D.; Lefering, R.; Legrand, V.; Lejeune, A.; Levi, L.; Lightfoot, R.; Lingsma, H.; Maegele, M.; Majdan, M.; Manara, A.; Manley, G.; Marechal, H.; Martino, C.; Mattern, J.; Mcmahon, C.; Melegh, B.; Menovsky, T.; Mikolic, A.; Misset, B.; Muraleedharan, V.; Murray, L.; Nair, N.; Negru, A.; Nelson, D.; Nieboer, D.; Nyiradi, J.; Oresic, M.; Ortolano, F.; Otesile, O.; Palotie, A.; Parizel, P.M.; Payen, J.-.; Perera, N.; Perlbarg, V.; Persona, P.; Peul, W.; Piippo-Karjalainen, A.; Pirinen, M.; Pisica, D.; Ples, H.; Polinder, S.; Pomposo, I.; Posti, J.P.; Puybasset, L.; Radoi, A.; Ragauskas, A.; Raj, R.; Rambadagalla, M.; Helmrich, I.R.; Rhodes, J.; Richardson, S.; Richter, S.; Ripatti, S.; Rocka, S.; Roe, C.; Roise, O.; Rosand, J.; Rosenfeld, J.; Rosenlund, C.; Rosenthal, G.; Rossaint, R.; Rossi, S.; Rueckert, D.; Rusnak, M.; Sahuquillo, J.; Sakowitz, O.; Sanchez-Porras, R.; Sandor, J.; Schafer, N.; Schmidt, S.; Schoechl, H.; Schoonman, G.; Schou, R.F.; Schwendenwein, E.; Singh, R.D.; Sewalt, C.; Skandsen, T.; Smielewski, P.; Sorinola, A.; Stamatakis, E.; Stanworth, S.; Stevens, R.; Stewart, W.; Steyerberg, E.W.; Stocchetti, N.; Sundstrom, N.; Takala, R.; Tamas, V.; Tamosuitis, T.; Taylor, M.S.; B. T., A.; Tenovuo, O.; Theadom, A.; Thomas, M.; Thibaut, A.; Tibboel, D.; Timmers, M.; Tolias, C.; Trapani, T.; Tudora, C.M.; Unterberg, A.; Vajkoczy, P.; Valeinis, E.; Vallance, S.; Vamos, Z.; Van Der Jagt, M.; Van Der Naalt, J.; Van Der Steen, G.; Van Dijck, J.T.J.M.; Van Erp, I.A.; Van Essen, T.A.; Van Hecke, W.; Van Heugten, C.; Van Praag, D.; Van Veen, E.; Van Wijk, R.P.J.; Vyvere, T.V.; Vargiolu, A.; Vega, E.; Velt, K.; Verheyden, J.; Vespa, P.M.; Vik, A.; Vilcinis, R.; Volovici, V.; Von Steinbuchel, N.; Voormolen, D.; Vulekovic, P.; Wang, K.K.W.; Wiegers, E.; Williams, G.; Winzeck, S.; Wolf, S.; Yang, Z.; Ylen, P.; Younsi, A.; Zeiler, F.A.; Zelinkova, V.; Ziverte, A.; Zoerle, T.

doi:10.1016/j.ebiom.2024.105298

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 - 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 fi lament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fi brillary acidic protein (GFAP) were assayed from serum sampled in the fi rst 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified fi ed 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 - 15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13-15 - 15 and positive CT (1.21-2.81), - 2.81), GCS 9-12 - 12 (1.16-2.02), - 2.02), GCS 3-8 - 8 (1.09-1.94). - 1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51-1.80) - 1.80) percentages of unfavourable outcome were 37-51% - 51% in the lowest quintiles of biomarker levels and reached 90-94% - 94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83-3.79), - 3.79), the percentages were 2-4% - 4% and 19-28% - 28% in the lowest and highest biomarker quintiles, respectively. Interpretation Conventional TBI severity classification fi cation is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity.

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 / L. Wilson, V.F.J. Newcombe, D.P. Whitehouse, S. Mondello, A.I.R. Maas, D.K. Menon, C. Ackerlund, K. Amrein, N. Andelic, L. Andreassen, A. Anke, A. Antoni, G. Audibert, P. Azouvi, M.L. Azzolini, R. Bartels, P. Barzo, R. Beauvais, R. Beer, B.-. Bellander, A. Belli, H. Benali, M. Berardino, L. Beretta, M. Blaabjerg, P. Bragge, A. Brazinova, V. Brinck, J. Brooker, C. Brorsson, A. Buki, M. Bullinger, M. Cabeleira, A. Caccioppola, E. Calappi, M.R. Calvi, P. Cameron, G.C. Lozano, M. Carbonara, A.M. Castano-Leon, S. Cavallo, G. Chevallard, A. Chieregato, G. Citerio, H. Clusmann, M.S. Coburn, J. Coles, J.D. Cooper, M. Correia, A. Covic, N. Curry, E. Czeiter, M. Czosnyka, C. Dahyot-Fizelier, P. Dark, H. Dawes, V. De Keyser, V. Degos, F. Della Corte, H.D. Boogert, B. Depreitere, D. Dilvesi, A. Dixit, E. Donoghue, J. Dreier, G.-. Duliere, A. Ercole, P. Esser, E. Ezer, M. Fabricius, V.L. Feigin, K. Foks, S. Frisvold, A. Furmanov, P. Gagliardo, D. Galanaud, D. Gantner, G. Gao, P. George, A. Ghuysen, L. Giga, B. Glocker, J. Golubovic, P.A. Gomez, J. Gratz, B. Gravesteijn, F. Grossi, R.L. Gruen, D. Gupta, J.A. Haagsma, I. Haitsma, R. Helbok, E. Helseth, L. Horton, J. Huijben, P.J. Hutchinson, B. Jacobs, S. Jankowski, M. Jarrett, J.-. Jiang, F. Johnson, K. Jones, M. Karan, A.G. Kolias, E. Kompanje, D. Kondziella, E. Kornaropoulos, L.-. Koskinen, N. Kovacs, A. Kowark, A. Lagares, L. Lanyon, S. Laureys, F. Lecky, D. Ledoux, R. Lefering, V. Legrand, A. Lejeune, L. Levi, R. Lightfoot, H. Lingsma, M. Maegele, M. Majdan, A. Manara, G. Manley, H. Marechal, C. Martino, J. Mattern, C. Mcmahon, B. Melegh, T. Menovsky, A. Mikolic, B. Misset, V. Muraleedharan, L. Murray, N. Nair, A. Negru, D. Nelson, D. Nieboer, J. Nyiradi, M. Oresic, F. Ortolano, O. Otesile, A. Palotie, P.M. Parizel, J.-. Payen, N. Perera, V. Perlbarg, P. Persona, W. Peul, A. Piippo-Karjalainen, M. Pirinen, D. Pisica, H. Ples, S. Polinder, I. Pomposo, J.P. Posti, L. Puybasset, A. Radoi, A. Ragauskas, R. Raj, M. Rambadagalla, I.R. Helmrich, J. Rhodes, S. Richardson, S. Richter, S. Ripatti, S. Rocka, C. Roe, O. Roise, J. Rosand, J. Rosenfeld, C. Rosenlund, G. Rosenthal, R. Rossaint, S. Rossi, D. Rueckert, M. Rusnak, J. Sahuquillo, O. Sakowitz, R. Sanchez-Porras, J. Sandor, N. Schafer, S. Schmidt, H. Schoechl, G. Schoonman, R.F. Schou, E. Schwendenwein, R.D. Singh, C. Sewalt, T. Skandsen, P. Smielewski, A. Sorinola, E. Stamatakis, S. Stanworth, R. Stevens, W. Stewart, E.W. Steyerberg, N. Stocchetti, N. Sundstrom, R. Takala, V. Tamas, T. Tamosuitis, M.S. Taylor, B.T. Ao, O. Tenovuo, A. Theadom, M. Thomas, A. Thibaut, D. Tibboel, M. Timmers, C. Tolias, T. Trapani, C.M. Tudora, A. Unterberg, P. Vajkoczy, E. Valeinis, S. Vallance, Z. Vamos, M. Van Der Jagt, J. Van Der Naalt, G. Van Der Steen, J.T.J.M. Van Dijck, I.A. Van Erp, T.A. Van Essen, W. Van Hecke, C. Van Heugten, D. Van Praag, E. Van Veen, R.P.J. Van Wijk, T.V. Vyvere, A. Vargiolu, E. Vega, K. Velt, J. Verheyden, P.M. Vespa, A. Vik, R. Vilcinis, V. Volovici, N. Von Steinbuchel, D. Voormolen, P. Vulekovic, K.K.W. Wang, E. Wiegers, G. Williams, S. Winzeck, S. Wolf, Z. Yang, P. Ylen, A. Younsi, F.A. Zeiler, V. Zelinkova, A. Ziverte, T. Zoerle. - In: EBIOMEDICINE. - ISSN 2352-3964. - 107:(2024), pp. 105298.1-105298.13. [10.1016/j.ebiom.2024.105298]

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 L.;Newcombe V. F. J.;Whitehouse D. P.;Mondello S.;Maas A. I. R.;Menon D. K.;Ackerlund C.;Amrein K.;Andelic N.;Andreassen L.;Anke A.;Antoni A.;Audibert G.;Azouvi P.;Azzolini M. L.;Bartels R.;Barzo P.;Beauvais R.;Beer R.;Bellander B. -M.;Belli A.;Benali H.;Berardino M.;Beretta L.;Blaabjerg M.;Bragge P.;Brazinova A.;Brinck V.;Brooker J.;Brorsson C.;Buki A.;Bullinger M.;Cabeleira M.;A. Caccioppola;Calappi E.;Calvi M. R.;Cameron P.;Lozano G. C.;Carbonara M.;Castano-Leon A. M.;Cavallo S.;G. Chevallard;Chieregato A.;Citerio G.;Clusmann H.;Coburn M. S.;Coles J.;Cooper J. D.;Correia M.;Covic A.;Curry N.;Czeiter E.;Czosnyka M.;Dahyot-Fizelier C.;Dark P.;Dawes H.;De Keyser V.;Degos V.;Della Corte F.;Boogert H. D.;Depreitere B.;Dilvesi D.;Dixit A.;Donoghue E.;Dreier J.;Duliere G. -L.;Ercole A.;Esser P.;Ezer E.;Fabricius M.;Feigin V. L.;Foks K.;Frisvold S.;Furmanov A.;Gagliardo P.;Galanaud D.;Gantner D.;Gao G.;George P.;Ghuysen A.;Giga L.;Glocker B.;Golubovic J.;Gomez P. A.;Gratz J.;Gravesteijn B.;Grossi F.;Gruen R. L.;Gupta D.;Haagsma J. A.;Haitsma I.;Helbok R.;Helseth E.;Horton L.;Huijben J.;Hutchinson P. J.;Jacobs B.;Jankowski S.;Jarrett M.;Jiang J. -Y.;Johnson F.;Jones K.;Karan M.;Kolias A. G.;Kompanje E.;Kondziella D.;Kornaropoulos E.;Koskinen L. -O.;Kovacs N.;Kowark A.;Lagares A.;Lanyon L.;Laureys S.;Lecky F.;Ledoux D.;Lefering R.;Legrand V.;Lejeune A.;L. Levi;Lightfoot R.;Lingsma H.;Maegele M.;Majdan M.;Manara A.;Manley G.;Marechal H.;Martino C.;Mattern J.;McMahon C.;Melegh B.;Menovsky T.;Mikolic A.;Misset B.;Muraleedharan V.;L. Murray;Nair N.;Negru A.;Nelson D.;Nieboer D.;Nyiradi J.;Oresic M.;F. Ortolano;Otesile O.;Palotie A.;Parizel P. M.;Payen J. -F.;Perera N.;Perlbarg V.;Persona P.;Peul W.;Piippo-Karjalainen A.;Pirinen M.;Pisica D.;Ples H.;Polinder S.;Pomposo I.;Posti J. P.;Puybasset L.;Radoi A.;Ragauskas A.;Raj R.;Rambadagalla M.;Helmrich I. R.;Rhodes J.;Richardson S.;Richter S.;Ripatti S.;Rocka S.;Roe C.;Roise O.;Rosand J.;Rosenfeld J.;Rosenlund C.;Rosenthal G.;Rossaint R.;Rossi S.;Rueckert D.;Rusnak M.;Sahuquillo J.;Sakowitz O.;Sanchez-Porras R.;Sandor J.;Schafer N.;Schmidt S.;Schoechl H.;Schoonman G.;Schou R. F.;Schwendenwein E.;Singh R. D.;Sewalt C.;Skandsen T.;Smielewski P.;Sorinola A.;Stamatakis E.;Stanworth S.;Stevens R.;Stewart W.;Steyerberg E. W.;N. Stocchetti;Sundstrom N.;Takala R.;Tamas V.;Tamosuitis T.;Taylor M. S.;Ao B. T.;Tenovuo O.;Theadom A.;Thomas M.;Thibaut A.;Tibboel D.;Timmers M.;Tolias C.;Trapani T.;Tudora C. M.;Unterberg A.;Vajkoczy P.;Valeinis E.;Vallance S.;Vamos Z.;van der Jagt M.;van der Naalt J.;Van der Steen G.;van Dijck J. T. J. M.;van Erp I. A.;van Essen T. A.;Van Hecke W.;van Heugten C.;Van Praag D.;van Veen E.;van Wijk R. P. J.;Vyvere T. V.;Vargiolu A.;Vega E.;Velt K.;Verheyden J.;Vespa P. M.;Vik A.;Vilcinis R.;Volovici V.;von Steinbuchel N.;Voormolen D.;Vulekovic P.;Wang K. K. W.;Wiegers E.;Williams G.;Winzeck S.;Wolf S.;Yang Z.;Ylen P.;Younsi A.;Zeiler F. A.;Zelinkova V.;Ziverte A.;T. Zoerle

2024

Abstract

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 - 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 fi lament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fi brillary acidic protein (GFAP) were assayed from serum sampled in the fi rst 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified fi ed 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 - 15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13-15 - 15 and positive CT (1.21-2.81), - 2.81), GCS 9-12 - 12 (1.16-2.02), - 2.02), GCS 3-8 - 8 (1.09-1.94). - 1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51-1.80) - 1.80) percentages of unfavourable outcome were 37-51% - 51% in the lowest quintiles of biomarker levels and reached 90-94% - 94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83-3.79), - 3.79), the percentages were 2-4% - 4% and 19-28% - 28% in the lowest and highest biomarker quintiles, respectively. Interpretation Conventional TBI severity classification fi cation is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity.

Scheda breve

Scheda completa

Scheda completa (DC)

	Parole chiave
	
				Blood biomarkers; GFAP; NFL; Outcomes; Traumatic brain injury; UCH-L1
			
	Settori scientifico-disciplinari dell'articolo (validi dal 09/05/2024)
	
				Settore MEDS-23/A - Anestesiologia
			
	Data di pubblicazione
	
				2024
			
	Rivista in ANCE
	
				EBIOMEDICINE
			
	DOI
	
				https://dx.doi.org/10.1016/j.ebiom.2024.105298
			
	Tipologia
	
				Article (author)
			
	Appare nelle tipologie:
	
				01 - Articolo su periodico

File in questo prodotto:

File	Dimensione	Formato
1-s2.0-S2352396424003347-main.pdf accesso aperto Tipologia: Publisher's version/PDF Licenza: Creative commons Dimensione 486.02 kB Formato Adobe PDF Visualizza/Apri	486.02 kB	Adobe PDF	Visualizza/Apri

Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1215144

Citazioni

0

12

11

15

IRIS Institutional Research Information System - AIR Archivio Istituzionale della Ricerca