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
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. Exposure–response relationships were investigated in 2479 patients aged ≥16...
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| Veröffentlicht in: | EBioMedicine 2024-09, Vol.107, p.105298, Article 105298 |
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| creator | Mondello, Stefania Maas, Andrew I.R. Amrein, Krisztina Andreassen, Lasse Anke, Audny Antoni, Anna Audibert, Gérard Azzolini, Maria Luisa Bartels, Ronald Barzó, Pál Bellander, Bo-Michael Belli, Antonio Benali, Habib Beretta, Luigi Brazinova, Alexandra Brooker, Joanne Brorsson, Camilla Citerio, Giuseppe Dawes, Helen De Keyser, Véronique Della Corte, Francesco Depreitere, Bart Dixit, Abhishek Ercole, Ari Fabricius, Martin Feigin, Valery L. Foks, Kelly Gao, Guoyi Giga, Lelde Golubović, Jagoš Gravesteijn, Benjamin Grossi, Francesca Gruen, Russell L. Gupta, Deepak Helbok, Raimund Helseth, Eirik Horton, Lindsay Jacobs, Bram Jiang, Ji-yao Jones, Kelly Koskinen, Lars-Owe Lanyon, Linda Laureys, Steven Lefering, Rolf Manara, Alex Maréchal, Hugues Martino, Costanza Mattern, Julia McMahon, Catherine Melegh, Béla Menovsky, Tomas Misset, Benoit Nieboer, Daan Oresic, Matej Otesile, Olubukola Palotie, Aarno Perlbarg, Vincent Pisica, Dana Polinder, Suzanne Pomposo, Inigo Puybasset, Louis Rădoi, Andreea Ragauskas, Arminas Helmrich, Isabel Retel Rhodes, Jonathan Ripatti, Samuli Rocka, Saulius Rosenfeld, Jeffrey Rossaint, Rolf Rossi, Sandra Sahuquillo, Juan Sakowitz, Oliver Sandor, Janos Schoonman, Guus Sorinola, Abayomi Stamatakis, Emmanuel Stanworth, Simon Stevens, Robert Steyerberg, Ewout W. Taylor, Mark Steven Tenovuo, Olli Thomas, Matt Thibaut, Aurore Tibboel, Dick Van der Steen, Gregory van Dijck, Jeroen T.J.M. van Erp, Inge A. Van Hecke, Wim van Heugten, Caroline van Veen, Ernest van Wijk, Roel P.J. Vyvere, Thijs Vande Velt, Kimberley Verheyden, Jan Vik, Anne Vilcinis, Rimantas Volovici, Victor von Steinbüchel, Nicole Ziverte, Agate Zoerle, Tommaso |
| description | 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.
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.
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.
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.
European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust. |
| doi_str_mv | 10.1016/j.ebiom.2024.105298 |
| format | Article |
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Maas, Andrew I.R. ; Amrein, Krisztina ; Andreassen, Lasse ; Anke, Audny ; Antoni, Anna ; Audibert, Gérard ; Azzolini, Maria Luisa ; Bartels, Ronald ; Barzó, Pál ; Bellander, Bo-Michael ; Belli, Antonio ; Benali, Habib ; Beretta, Luigi ; Brazinova, Alexandra ; Brooker, Joanne ; Brorsson, Camilla ; Citerio, Giuseppe ; Dawes, Helen ; De Keyser, Véronique ; Della Corte, Francesco ; Depreitere, Bart ; Dixit, Abhishek ; Ercole, Ari ; Fabricius, Martin ; Feigin, Valery L. ; Foks, Kelly ; Gao, Guoyi ; Giga, Lelde ; Golubović, Jagoš ; Gravesteijn, Benjamin ; Grossi, Francesca ; Gruen, Russell L. ; Gupta, Deepak ; Helbok, Raimund ; Helseth, Eirik ; Horton, Lindsay ; Jacobs, Bram ; Jiang, Ji-yao ; Jones, Kelly ; Koskinen, Lars-Owe ; Lanyon, Linda ; Laureys, Steven ; Lefering, Rolf ; Manara, Alex ; Maréchal, Hugues ; Martino, Costanza ; Mattern, Julia ; McMahon, Catherine ; Melegh, Béla ; Menovsky, Tomas ; Misset, Benoit ; Nieboer, Daan ; Oresic, Matej ; Otesile, Olubukola ; Palotie, Aarno ; Perlbarg, Vincent ; Pisica, Dana ; Polinder, Suzanne ; Pomposo, Inigo ; Puybasset, Louis ; Rădoi, Andreea ; Ragauskas, Arminas ; Helmrich, Isabel Retel ; Rhodes, Jonathan ; Ripatti, Samuli ; Rocka, Saulius ; Rosenfeld, Jeffrey ; Rossaint, Rolf ; Rossi, Sandra ; Sahuquillo, Juan ; Sakowitz, Oliver ; Sandor, Janos ; Schoonman, Guus ; Sorinola, Abayomi ; Stamatakis, Emmanuel ; Stanworth, Simon ; Stevens, Robert ; Steyerberg, Ewout W. ; Taylor, Mark Steven ; Tenovuo, Olli ; Thomas, Matt ; Thibaut, Aurore ; Tibboel, Dick ; Van der Steen, Gregory ; van Dijck, Jeroen T.J.M. ; van Erp, Inge A. ; Van Hecke, Wim ; van Heugten, Caroline ; van Veen, Ernest ; van Wijk, Roel P.J. ; Vyvere, Thijs Vande ; Velt, Kimberley ; Verheyden, Jan ; Vik, Anne ; Vilcinis, Rimantas ; Volovici, Victor ; von Steinbüchel, Nicole ; Ziverte, Agate ; Zoerle, Tommaso</creator><creatorcontrib>Mondello, Stefania ; Maas, Andrew I.R. ; Amrein, Krisztina ; Andreassen, Lasse ; Anke, Audny ; Antoni, Anna ; Audibert, Gérard ; Azzolini, Maria Luisa ; Bartels, Ronald ; Barzó, Pál ; Bellander, Bo-Michael ; Belli, Antonio ; Benali, Habib ; Beretta, Luigi ; Brazinova, Alexandra ; Brooker, Joanne ; Brorsson, Camilla ; Citerio, Giuseppe ; Dawes, Helen ; De Keyser, Véronique ; Della Corte, Francesco ; Depreitere, Bart ; Dixit, Abhishek ; Ercole, Ari ; Fabricius, Martin ; Feigin, Valery L. ; Foks, Kelly ; Gao, Guoyi ; Giga, Lelde ; Golubović, Jagoš ; Gravesteijn, Benjamin ; Grossi, Francesca ; Gruen, Russell L. ; Gupta, Deepak ; Helbok, Raimund ; Helseth, Eirik ; Horton, Lindsay ; Jacobs, Bram ; Jiang, Ji-yao ; Jones, Kelly ; Koskinen, Lars-Owe ; Lanyon, Linda ; Laureys, Steven ; Lefering, Rolf ; Manara, Alex ; Maréchal, Hugues ; Martino, Costanza ; Mattern, Julia ; McMahon, Catherine ; Melegh, Béla ; Menovsky, Tomas ; Misset, Benoit ; Nieboer, Daan ; Oresic, Matej ; Otesile, Olubukola ; Palotie, Aarno ; Perlbarg, Vincent ; Pisica, Dana ; Polinder, Suzanne ; Pomposo, Inigo ; Puybasset, Louis ; Rădoi, Andreea ; Ragauskas, Arminas ; Helmrich, Isabel Retel ; Rhodes, Jonathan ; Ripatti, Samuli ; Rocka, Saulius ; Rosenfeld, Jeffrey ; Rossaint, Rolf ; Rossi, Sandra ; Sahuquillo, Juan ; Sakowitz, Oliver ; Sandor, Janos ; Schoonman, Guus ; Sorinola, Abayomi ; Stamatakis, Emmanuel ; Stanworth, Simon ; Stevens, Robert ; Steyerberg, Ewout W. ; Taylor, Mark Steven ; Tenovuo, Olli ; Thomas, Matt ; Thibaut, Aurore ; Tibboel, Dick ; Van der Steen, Gregory ; van Dijck, Jeroen T.J.M. ; van Erp, Inge A. ; Van Hecke, Wim ; van Heugten, Caroline ; van Veen, Ernest ; van Wijk, Roel P.J. ; Vyvere, Thijs Vande ; Velt, Kimberley ; Verheyden, Jan ; Vik, Anne ; Vilcinis, Rimantas ; Volovici, Victor ; von Steinbüchel, Nicole ; Ziverte, Agate ; Zoerle, Tommaso ; CENTER-TBI participants and investigators</creatorcontrib><description>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.
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.
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.
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.
European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.</description><identifier>ISSN: 2352-3964</identifier><identifier>EISSN: 2352-3964</identifier><identifier>DOI: 10.1016/j.ebiom.2024.105298</identifier><identifier>PMID: 39191173</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Blood biomarkers ; GFAP ; Human health and pathology ; Life Sciences ; NFL ; Outcomes ; Traumatic brain injury ; UCH-L1</subject><ispartof>EBioMedicine, 2024-09, Vol.107, p.105298, Article 105298</ispartof><rights>2024 The Author(s)</rights><rights>Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c273t-66a5275a094a8fc4e1f341aeac331c7caed43b69ee32625c8852fe7ce3663e6a3</cites><orcidid>0000-0003-1612-1264 ; 0000-0003-4113-2328 ; 0000-0002-6849-1825</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,864,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39191173$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04831128$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Mondello, Stefania</creatorcontrib><creatorcontrib>Maas, Andrew I.R.</creatorcontrib><creatorcontrib>Amrein, 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Dick</creatorcontrib><creatorcontrib>Van der Steen, Gregory</creatorcontrib><creatorcontrib>van Dijck, Jeroen T.J.M.</creatorcontrib><creatorcontrib>van Erp, Inge A.</creatorcontrib><creatorcontrib>Van Hecke, Wim</creatorcontrib><creatorcontrib>van Heugten, Caroline</creatorcontrib><creatorcontrib>van Veen, Ernest</creatorcontrib><creatorcontrib>van Wijk, Roel P.J.</creatorcontrib><creatorcontrib>Vyvere, Thijs Vande</creatorcontrib><creatorcontrib>Velt, Kimberley</creatorcontrib><creatorcontrib>Verheyden, Jan</creatorcontrib><creatorcontrib>Vik, Anne</creatorcontrib><creatorcontrib>Vilcinis, Rimantas</creatorcontrib><creatorcontrib>Volovici, Victor</creatorcontrib><creatorcontrib>von Steinbüchel, Nicole</creatorcontrib><creatorcontrib>Ziverte, Agate</creatorcontrib><creatorcontrib>Zoerle, Tommaso</creatorcontrib><creatorcontrib>CENTER-TBI participants and investigators</creatorcontrib><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</title><title>EBioMedicine</title><addtitle>EBioMedicine</addtitle><description>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.
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.
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.
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.
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Stefania ; Maas, Andrew I.R. ; Amrein, Krisztina ; Andreassen, Lasse ; Anke, Audny ; Antoni, Anna ; Audibert, Gérard ; Azzolini, Maria Luisa ; Bartels, Ronald ; Barzó, Pál ; Bellander, Bo-Michael ; Belli, Antonio ; Benali, Habib ; Beretta, Luigi ; Brazinova, Alexandra ; Brooker, Joanne ; Brorsson, Camilla ; Citerio, Giuseppe ; Dawes, Helen ; De Keyser, Véronique ; Della Corte, Francesco ; Depreitere, Bart ; Dixit, Abhishek ; Ercole, Ari ; Fabricius, Martin ; Feigin, Valery L. ; Foks, Kelly ; Gao, Guoyi ; Giga, Lelde ; Golubović, Jagoš ; Gravesteijn, Benjamin ; Grossi, Francesca ; Gruen, Russell L. ; Gupta, Deepak ; Helbok, Raimund ; Helseth, Eirik ; Horton, Lindsay ; Jacobs, Bram ; Jiang, Ji-yao ; Jones, Kelly ; Koskinen, Lars-Owe ; Lanyon, Linda ; Laureys, Steven ; Lefering, Rolf ; Manara, Alex ; Maréchal, Hugues ; Martino, Costanza ; Mattern, Julia ; McMahon, Catherine ; Melegh, Béla ; Menovsky, Tomas ; Misset, Benoit ; Nieboer, Daan ; Oresic, Matej ; Otesile, Olubukola ; Palotie, Aarno ; Perlbarg, Vincent ; Pisica, Dana ; Polinder, Suzanne ; Pomposo, Inigo ; Puybasset, Louis ; Rădoi, Andreea ; Ragauskas, Arminas ; Helmrich, Isabel Retel ; Rhodes, Jonathan ; Ripatti, Samuli ; Rocka, Saulius ; Rosenfeld, Jeffrey ; Rossaint, Rolf ; Rossi, Sandra ; Sahuquillo, Juan ; Sakowitz, Oliver ; Sandor, Janos ; Schoonman, Guus ; Sorinola, Abayomi ; Stamatakis, Emmanuel ; Stanworth, Simon ; Stevens, Robert ; Steyerberg, Ewout W. ; Taylor, Mark Steven ; Tenovuo, Olli ; Thomas, Matt ; Thibaut, Aurore ; Tibboel, Dick ; Van der Steen, Gregory ; van Dijck, Jeroen T.J.M. ; van Erp, Inge A. ; Van Hecke, Wim ; van Heugten, Caroline ; van Veen, Ernest ; van Wijk, Roel P.J. ; Vyvere, Thijs Vande ; Velt, Kimberley ; Verheyden, Jan ; Vik, Anne ; Vilcinis, Rimantas ; Volovici, Victor ; von Steinbüchel, Nicole ; Ziverte, Agate ; Zoerle, 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mondello, Stefania</au><au>Maas, Andrew I.R.</au><au>Amrein, Krisztina</au><au>Andreassen, Lasse</au><au>Anke, Audny</au><au>Antoni, Anna</au><au>Audibert, Gérard</au><au>Azzolini, Maria Luisa</au><au>Bartels, Ronald</au><au>Barzó, Pál</au><au>Bellander, Bo-Michael</au><au>Belli, Antonio</au><au>Benali, Habib</au><au>Beretta, Luigi</au><au>Brazinova, Alexandra</au><au>Brooker, Joanne</au><au>Brorsson, Camilla</au><au>Citerio, Giuseppe</au><au>Dawes, Helen</au><au>De Keyser, Véronique</au><au>Della Corte, Francesco</au><au>Depreitere, Bart</au><au>Dixit, Abhishek</au><au>Ercole, Ari</au><au>Fabricius, Martin</au><au>Feigin, Valery L.</au><au>Foks, Kelly</au><au>Gao, Guoyi</au><au>Giga, Lelde</au><au>Golubović, Jagoš</au><au>Gravesteijn, Benjamin</au><au>Grossi, Francesca</au><au>Gruen, Russell L.</au><au>Gupta, Deepak</au><au>Helbok, Raimund</au><au>Helseth, Eirik</au><au>Horton, Lindsay</au><au>Jacobs, Bram</au><au>Jiang, Ji-yao</au><au>Jones, Kelly</au><au>Koskinen, Lars-Owe</au><au>Lanyon, Linda</au><au>Laureys, Steven</au><au>Lefering, Rolf</au><au>Manara, Alex</au><au>Maréchal, Hugues</au><au>Martino, Costanza</au><au>Mattern, Julia</au><au>McMahon, Catherine</au><au>Melegh, Béla</au><au>Menovsky, Tomas</au><au>Misset, Benoit</au><au>Nieboer, Daan</au><au>Oresic, Matej</au><au>Otesile, Olubukola</au><au>Palotie, Aarno</au><au>Perlbarg, Vincent</au><au>Pisica, Dana</au><au>Polinder, Suzanne</au><au>Pomposo, Inigo</au><au>Puybasset, Louis</au><au>Rădoi, Andreea</au><au>Ragauskas, Arminas</au><au>Helmrich, Isabel Retel</au><au>Rhodes, Jonathan</au><au>Ripatti, Samuli</au><au>Rocka, Saulius</au><au>Rosenfeld, Jeffrey</au><au>Rossaint, Rolf</au><au>Rossi, Sandra</au><au>Sahuquillo, Juan</au><au>Sakowitz, Oliver</au><au>Sandor, Janos</au><au>Schoonman, Guus</au><au>Sorinola, Abayomi</au><au>Stamatakis, Emmanuel</au><au>Stanworth, Simon</au><au>Stevens, Robert</au><au>Steyerberg, Ewout W.</au><au>Taylor, Mark Steven</au><au>Tenovuo, Olli</au><au>Thomas, Matt</au><au>Thibaut, Aurore</au><au>Tibboel, Dick</au><au>Van der Steen, Gregory</au><au>van Dijck, Jeroen T.J.M.</au><au>van Erp, Inge A.</au><au>Van Hecke, Wim</au><au>van Heugten, Caroline</au><au>van Veen, Ernest</au><au>van Wijk, Roel P.J.</au><au>Vyvere, Thijs Vande</au><au>Velt, Kimberley</au><au>Verheyden, Jan</au><au>Vik, Anne</au><au>Vilcinis, Rimantas</au><au>Volovici, Victor</au><au>von Steinbüchel, Nicole</au><au>Ziverte, Agate</au><au>Zoerle, Tommaso</au><aucorp>CENTER-TBI participants and investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>EBioMedicine</jtitle><addtitle>EBioMedicine</addtitle><date>2024-09-01</date><risdate>2024</risdate><volume>107</volume><spage>105298</spage><pages>105298-</pages><artnum>105298</artnum><issn>2352-3964</issn><eissn>2352-3964</eissn><abstract>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.
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.
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.
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.
European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>39191173</pmid><doi>10.1016/j.ebiom.2024.105298</doi><orcidid>https://orcid.org/0000-0003-1612-1264</orcidid><orcidid>https://orcid.org/0000-0003-4113-2328</orcidid><orcidid>https://orcid.org/0000-0002-6849-1825</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2352-3964 |
| ispartof | EBioMedicine, 2024-09, Vol.107, p.105298, Article 105298 |
| issn | 2352-3964 2352-3964 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_04831128v1 |
| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Blood biomarkers GFAP Human health and pathology Life Sciences NFL Outcomes Traumatic brain injury UCH-L1 |
| 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 |
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