Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury

Mild traumatic brain injury (mTBI) patients may have trauma-induced brain lesions detectable using CT scans. However, most patients will be CT-negative. There is thus a need for an additional tool to detect patients at risk. Single blood biomarkers, such as S100B and GFAP, have been widely studied i...

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Autores: Lagerstedt, Linnéa, Egea Guerrero, Juan José, Bustamante, Alejandro, Rodríguez Rodríguez, Ana, El Rahal, Amir, Quintana-Díaz, Manuel, García-Armengol, Roser, Melinda Prica, Carmen, Montaner, Joan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/78193
Acceso en línea:https://hdl.handle.net/11441/78193
https://doi.org/10.1371/journal.pone.0200394
Access Level:acceso abierto
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spelling Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injuryLagerstedt, LinnéaEgea Guerrero, Juan JoséBustamante, AlejandroRodríguez Rodríguez, AnaEl Rahal, AmirQuintana-Díaz, ManuelGarcía-Armengol, RoserMelinda Prica, CarmenMontaner, JoanMild traumatic brain injury (mTBI) patients may have trauma-induced brain lesions detectable using CT scans. However, most patients will be CT-negative. There is thus a need for an additional tool to detect patients at risk. Single blood biomarkers, such as S100B and GFAP, have been widely studied in mTBI patients, but to date, none seems to perform well enough. In many different diseases, combining several biomarkers into panels has become increasingly interesting for diagnoses and to enhance classification performance. The present study evaluated 13 proteins individually—H-FABP, MMP-1, MMP-3, MMP-9, VCAM, ICAM, SAA, CRP, GSTP, NKDA, PRDX1, DJ-1 and IL-10—for their capacity to differentiate between patients with and without a brain lesion according to CT results. The best performing proteins were then compared and combined with the S100B and GFAP proteins into a CT-scan triage panel. Patients diagnosed with mTBI, with a Glasgow Coma Scale score of 15 and one additional clinical symptom were enrolled at three different European sites. A blood sample was collected at hospital admission, and a CT scan was performed. Patients were divided into two two-centre cohorts and further dichotomised into CT-positive and CT-negative groups for statistical analysis. Single markers and panels were evaluated using Cohort 1. Four proteins—H-FABP, IL-10, S100B and GFAP—showed significantly higher levels in CT-positive patients. The best-performing biomarker was H-FABP, with a specificity of 32% (95% CI 23–40) and sensitivity reaching 100%. The best-performing two-marker panel for Cohort 1, subsequently validated in Cohort 2, was a combination of H-FABP and GFAP, enhancing specificity to 46% (95% CI 36–55). When adding IL-10 to this panel, specificity reached 52% (95% CI 43–61) with 100% sensitivity. These results showed that proteins combined into panels could be used to efficiently classify CT-positive and CT-negative mTBI patients.Public Library of Science2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/78193https://doi.org/10.1371/journal.pone.0200394reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésPlos One, 13 (7), e0200394-1-e0200394-13.https://doi.org/10.1371/journal.pone.0200394info:eu-repo/semantics/openAccessoai:idus.us.es:11441/781932026-06-17T12:51:07Z
dc.title.none.fl_str_mv Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury
title Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury
spellingShingle Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury
Lagerstedt, Linnéa
title_short Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury
title_full Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury
title_fullStr Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury
title_full_unstemmed Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury
title_sort Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury
dc.creator.none.fl_str_mv Lagerstedt, Linnéa
Egea Guerrero, Juan José
Bustamante, Alejandro
Rodríguez Rodríguez, Ana
El Rahal, Amir
Quintana-Díaz, Manuel
García-Armengol, Roser
Melinda Prica, Carmen
Montaner, Joan
author Lagerstedt, Linnéa
author_facet Lagerstedt, Linnéa
Egea Guerrero, Juan José
Bustamante, Alejandro
Rodríguez Rodríguez, Ana
El Rahal, Amir
Quintana-Díaz, Manuel
García-Armengol, Roser
Melinda Prica, Carmen
Montaner, Joan
author_role author
author2 Egea Guerrero, Juan José
Bustamante, Alejandro
Rodríguez Rodríguez, Ana
El Rahal, Amir
Quintana-Díaz, Manuel
García-Armengol, Roser
Melinda Prica, Carmen
Montaner, Joan
author2_role author
author
author
author
author
author
author
author
description Mild traumatic brain injury (mTBI) patients may have trauma-induced brain lesions detectable using CT scans. However, most patients will be CT-negative. There is thus a need for an additional tool to detect patients at risk. Single blood biomarkers, such as S100B and GFAP, have been widely studied in mTBI patients, but to date, none seems to perform well enough. In many different diseases, combining several biomarkers into panels has become increasingly interesting for diagnoses and to enhance classification performance. The present study evaluated 13 proteins individually—H-FABP, MMP-1, MMP-3, MMP-9, VCAM, ICAM, SAA, CRP, GSTP, NKDA, PRDX1, DJ-1 and IL-10—for their capacity to differentiate between patients with and without a brain lesion according to CT results. The best performing proteins were then compared and combined with the S100B and GFAP proteins into a CT-scan triage panel. Patients diagnosed with mTBI, with a Glasgow Coma Scale score of 15 and one additional clinical symptom were enrolled at three different European sites. A blood sample was collected at hospital admission, and a CT scan was performed. Patients were divided into two two-centre cohorts and further dichotomised into CT-positive and CT-negative groups for statistical analysis. Single markers and panels were evaluated using Cohort 1. Four proteins—H-FABP, IL-10, S100B and GFAP—showed significantly higher levels in CT-positive patients. The best-performing biomarker was H-FABP, with a specificity of 32% (95% CI 23–40) and sensitivity reaching 100%. The best-performing two-marker panel for Cohort 1, subsequently validated in Cohort 2, was a combination of H-FABP and GFAP, enhancing specificity to 46% (95% CI 36–55). When adding IL-10 to this panel, specificity reached 52% (95% CI 43–61) with 100% sensitivity. These results showed that proteins combined into panels could be used to efficiently classify CT-positive and CT-negative mTBI patients.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/78193
https://doi.org/10.1371/journal.pone.0200394
url https://hdl.handle.net/11441/78193
https://doi.org/10.1371/journal.pone.0200394
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Plos One, 13 (7), e0200394-1-e0200394-13.
https://doi.org/10.1371/journal.pone.0200394
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
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