TY - JOUR
T1 - Correlation of blood biomarkers and biomarker panels with traumatic findings on computed tomography after traumatic brain injury
AU - Posti, Jussi P.
AU - Takala, Riikka S.K.
AU - Lagerstedt, Linneá
AU - Dickens, Alex M.
AU - Hossain, Iftakher
AU - Mohammadian, Mehrbod
AU - Ala-Seppälä, Henna
AU - Frantzén, Janek
AU - van Gils, Mark
AU - Hutchinson, Peter J.
AU - Katila, Ari J.
AU - Maanpaä, Henna Riikka
AU - Menon, David K.
AU - Newcombe, Virginia F.
AU - Tallus, Jussi
AU - Hrusovsky, Kevin
AU - Wilson, David H.
AU - Gill, Jessica
AU - Sanchez, Jean Charles
AU - Tenovuo, Olli
AU - Zetterberg, Henrik
AU - Blennow, Kaj
N1 - Funding Information:
This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), Government’s Special Financial Transfer tied to academic research in Health Sciences (Finland; JPP), Emil Aaltonen Foundation sr ( JPP), Finnish Brain Foundation sr ( JPP), Maire Taponen
Funding Information:
Foundation ( JPP), Integra EANS Research Grant (IH), University of Turku Graduate School funding (MM), National Institute for Health Research (NIHR) Research Professorship and the NIHR Cambridge BRC (PJH), NIHR Research UK (through a Senior Investigator Award and the Cambridge Biomedical Research Centre; DKM); Academy of Medical Sciences/Health Foundation Clinician Scientist Fellowship (VFN); Wallenberg Academy Fellowship and grants from the Swedish and European Research Councils (HZ), Torsten Söderberg Professorship in Medicine, award by the Royal Swedish Academy of Sciences, grants from the Swedish Research Council (KB). The authors thank our research nurses Patricia Bertenyi and Satu Honkala for their valuable contribution to this study.
Funding Information:
Funding: This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), Government’s Special Financial Transfer tied to academic research in Health Sciences (Finland) ( JPP), Emil Aaltonen Foundation ( JPP), Finnish Brain Foundation ( JPP), Integra EANS Research Grant (IH), University of Turku Graduate School funding (MM), NIHR Research Professorship and the NIHR Cambridge BRC (PJH), NIHR Research UK (through a Senior Investigator Award and the Cambridge Biomedical Research Centre) (DKM), Academy of Medical Sciences/The Health Foundation Clinician Scientist Fellowship (VFN); Wallenberg Academy Fellowship and grants from the Swedish and European Research Councils (HZ), Torsten Söderberg Professorship in Medicine, award by the Royal Swedish Academy of Sciences, grants from the Swedish Research Council (KB).
Funding Information:
Riikka S.K. Takala has no competing financial interests. RSKT has received speakers’ fees from Abbott, Fresenius-Kabi, Orion corporation and UCB, conference funding from Pfizer and Ster-ipolar and is stockholder of Orion.
Publisher Copyright:
© 2019 Mary Ann Liebert, Inc., publishers.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/7/15
Y1 - 2019/7/15
N2 - The aim of the study was to examine the ability of eight protein biomarkers and their combinations in discriminating computed tomography (CT)-negative and CT-positive patients with traumatic brain injury (TBI), utilizing highly sensitive immunoassays in a well-characterized cohort. Blood samples were obtained from 160 patients with acute TBI within 24 h of admission. Levels of β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42), glial fibrillary acidic protein (GFAP), heart fatty-acid binding protein (H-FABP), interleukin 10 (IL-10), neurofilament light (NF-L), S100 calcium-binding protein B (S100B), and tau were measured. Patients were divided into CT-negative (n = 65) and CT-positive (n = 95), and analyses were conducted separately for TBIs of all severities (Glasgow Coma Scale [GCS] score 3-15) and mild TBIs (mTBIs; GCS 13-15). NF-L, GFAP, and tau were the best in discriminating CT-negative and CT-positive patients, both in patients with mTBI and with all severities. In patients with all severities, area under the curve of the receiver operating characteristic (AUC) was 0.822, 0.817, and 0.781 for GFAP, NF-L, and tau, respectively. In patients with mTBI, AUC was 0.720, 0.689, and 0.676, for GFAP, tau, and NF-L, respectively. The best panel of three biomarkers for discriminating CT-negative and CT-positive patients in the group of all severities was a combination of GFAP+H-FABP+IL-10, with a sensitivity of 100% and specificity of 38.5%. In patients with mTBI, the best panel of three biomarkers was H-FABP+S100B+tau, with a sensitivity of 100% and specificity of 46.4%. Panels of biomarkers outperform individual biomarkers in separating CT-negative and CT-positive patients. Panels consisted mainly of different biomarkers than those that performed best as an individual biomarker.
AB - The aim of the study was to examine the ability of eight protein biomarkers and their combinations in discriminating computed tomography (CT)-negative and CT-positive patients with traumatic brain injury (TBI), utilizing highly sensitive immunoassays in a well-characterized cohort. Blood samples were obtained from 160 patients with acute TBI within 24 h of admission. Levels of β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42), glial fibrillary acidic protein (GFAP), heart fatty-acid binding protein (H-FABP), interleukin 10 (IL-10), neurofilament light (NF-L), S100 calcium-binding protein B (S100B), and tau were measured. Patients were divided into CT-negative (n = 65) and CT-positive (n = 95), and analyses were conducted separately for TBIs of all severities (Glasgow Coma Scale [GCS] score 3-15) and mild TBIs (mTBIs; GCS 13-15). NF-L, GFAP, and tau were the best in discriminating CT-negative and CT-positive patients, both in patients with mTBI and with all severities. In patients with all severities, area under the curve of the receiver operating characteristic (AUC) was 0.822, 0.817, and 0.781 for GFAP, NF-L, and tau, respectively. In patients with mTBI, AUC was 0.720, 0.689, and 0.676, for GFAP, tau, and NF-L, respectively. The best panel of three biomarkers for discriminating CT-negative and CT-positive patients in the group of all severities was a combination of GFAP+H-FABP+IL-10, with a sensitivity of 100% and specificity of 38.5%. In patients with mTBI, the best panel of three biomarkers was H-FABP+S100B+tau, with a sensitivity of 100% and specificity of 46.4%. Panels of biomarkers outperform individual biomarkers in separating CT-negative and CT-positive patients. Panels consisted mainly of different biomarkers than those that performed best as an individual biomarker.
KW - biomarkers
KW - computed tomography
KW - traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=85068507796&partnerID=8YFLogxK
U2 - 10.1089/neu.2018.6254
DO - 10.1089/neu.2018.6254
M3 - Article
C2 - 30760178
AN - SCOPUS:85068507796
SN - 0897-7151
VL - 36
SP - 2178
EP - 2189
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 14
ER -