Observational studyNeurology2025
Association of Blood-Based Biomarkers and 6-Month Patient-Reported Outcomes in Patients With Mild TBI: A CENTER-TBI Analysis.
Abstract readObservational StudyMulticenter Study
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Observational study in Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10citing papers in PubMed
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What it found
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The trial behind it
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Who cites it
10 citing papers in PubMed.
- Blood-Based Biomarkers and Cognitive-Behavioral Assessment in Mild Traumatic Brain Injury: Current Evidence and Clinical Perspectives.Korean journal of neurotrauma · 2026Review
- Near-care assay of plasma glial fibrillary acid protein and ubiquitin carboxyl-terminal hydrolase isozyme L1 with shorter and prolonged duration exercise.Scientific reports · 2026Article
- A scoping review on the essential role of global neurotrauma in achieving the sustainable development goals.Discover public health · 2026Review
- The Role of Interleukins in Pediatric Traumatic Brain Injury: A Narrative Synthesis.Journal of clinical medicine · 2025Review
- Association between Neutrophil-to-Albumin Ratio and 28-Day All-Cause Mortality in Patients with Traumatic Brain Injury : A Retrospective Analysis of the MIMIC-IV Database.Journal of Korean Neurosurgical Society · 2025Article
- Reduced hospitalisations for paediatric mild traumatic brain injury: a nationwide observational study.BMJ paediatrics open · 2025Observational
- Detection of NLRP3, ASC, and Caspase-1 in serum and cerebrospinal fluid of traumatic brain injury patients: implications for short-term prognosis.Acta neurologica Belgica · 2025Article
- Brain injury biomarkers as targets for drugs development and personalized treatment for traumatic brain injury patients.Frontiers in pharmacology · 2025Review
- Assessment value of blood pressure variability combined with serum tau protein for the prognosis of patients with traumatic brain injury.Frontiers in neurologyArticle
- Noninvasive Urinary Biomarkers for Early Diagnosis of Mild Traumatic Brain Injury.Neurotrauma reportsArticle
Corrections and comments
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Authors and funding
12 authors.
Daniel P WhitehouseFrom the Perioperative, Acute, Critical Care and Emergency Medicine (PACE) (D.P.W., D.M., V.F.J.N.), Department of Medicine, University of Cambridge, Addenbrooke's Hospital; Division of Psychology (L.W.), University of Stirling, United Kingdom; Department of Neurosurgery (E.C.), Medical School, and Neurotrauma Research Group (E.C.), Szentagothai Research Centre, University of Pecs, Hungary; Department of Neurosurgery (A.B.), Faculty of Medicine and Health, Örebro University, Sweden; Department of Neurobiology (K.K.W.W.), Center for Neurotrauma, Multiomics & Biomarkers (CNMB) Neuroscience Institute, Morehouse School of Medicine (MSM), Atlanta, GA; Program for Neurotrauma, Neuroproteomics and Biomarker Research (K.K.W.W.), Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville; Institute of Psychology (N.v.S., M.Z.), University of Innsbruck; Faculty of Psychotherapy Science (M.Z.), Sigmund Freud University, Vienna, Austria; Department of Biomedical Data Sciences (E.S.), Leiden University Medical Center, the Netherlands; Department of Neurosurgery (A.I.R.M.), Antwerp University Hospital, Edegem; and Department of Translational Neuroscience (A.I.R.M.), Faculty of Medicine and Health Science, University of Antwerp, Belgium.ORCID 0000-0002-0216-1866
Lindsay WilsonFrom the Perioperative, Acute, Critical Care and Emergency Medicine (PACE) (D.P.W., D.M., V.F.J.N.), Department of Medicine, University of Cambridge, Addenbrooke's Hospital; Division of Psychology (L.W.), University of Stirling, United Kingdom; Department of Neurosurgery (E.C.), Medical School, and Neurotrauma Research Group (E.C.), Szentagothai Research Centre, University of Pecs, Hungary; Department of Neurosurgery (A.B.), Faculty of Medicine and Health, Örebro University, Sweden; Department of Neurobiology (K.K.W.W.), Center for Neurotrauma, Multiomics & Biomarkers (CNMB) Neuroscience Institute, Morehouse School of Medicine (MSM), Atlanta, GA; Program for Neurotrauma, Neuroproteomics and Biomarker Research (K.K.W.W.), Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville; Institute of Psychology (N.v.S., M.Z.), University of Innsbruck; Faculty of Psychotherapy Science (M.Z.), Sigmund Freud University, Vienna, Austria; Department of Biomedical Data Sciences (E.S.), Leiden University Medical Center, the Netherlands; Department of Neurosurgery (A.I.R.M.), Antwerp University Hospital, Edegem; and Department of Translational Neuroscience (A.I.R.M.), Faculty of Medicine and Health Science, University of Antwerp, Belgium.ORCID 0000-0003-4113-2328
Endre CzeiterFrom the Perioperative, Acute, Critical Care and Emergency Medicine (PACE) (D.P.W., D.M., V.F.J.N.), Department of Medicine, University of Cambridge, Addenbrooke's Hospital; Division of Psychology (L.W.), University of Stirling, United Kingdom; Department of Neurosurgery (E.C.), Medical School, and Neurotrauma Research Group (E.C.), Szentagothai Research Centre, University of Pecs, Hungary; Department of Neurosurgery (A.B.), Faculty of Medicine and Health, Örebro University, Sweden; Department of Neurobiology (K.K.W.W.), Center for Neurotrauma, Multiomics & Biomarkers (CNMB) Neuroscience Institute, Morehouse School of Medicine (MSM), Atlanta, GA; Program for Neurotrauma, Neuroproteomics and Biomarker Research (K.K.W.W.), Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville; Institute of Psychology (N.v.S., M.Z.), University of Innsbruck; Faculty of Psychotherapy Science (M.Z.), Sigmund Freud University, Vienna, Austria; Department of Biomedical Data Sciences (E.S.), Leiden University Medical Center, the Netherlands; Department of Neurosurgery (A.I.R.M.), Antwerp University Hospital, Edegem; and Department of Translational Neuroscience (A.I.R.M.), Faculty of Medicine and Health Science, University of Antwerp, Belgium.ORCID 0000-0002-9578-6944
Andras BukiFrom the Perioperative, Acute, Critical Care and Emergency Medicine (PACE) (D.P.W., D.M., V.F.J.N.), Department of Medicine, University of Cambridge, Addenbrooke's Hospital; Division of Psychology (L.W.), University of Stirling, United Kingdom; Department of Neurosurgery (E.C.), Medical School, and Neurotrauma Research Group (E.C.), Szentagothai Research Centre, University of Pecs, Hungary; Department of Neurosurgery (A.B.), Faculty of Medicine and Health, Örebro University, Sweden; Department of Neurobiology (K.K.W.W.), Center for Neurotrauma, Multiomics & Biomarkers (CNMB) Neuroscience Institute, Morehouse School of Medicine (MSM), Atlanta, GA; Program for Neurotrauma, Neuroproteomics and Biomarker Research (K.K.W.W.), Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville; Institute of Psychology (N.v.S., M.Z.), University of Innsbruck; Faculty of Psychotherapy Science (M.Z.), Sigmund Freud University, Vienna, Austria; Department of Biomedical Data Sciences (E.S.), Leiden University Medical Center, the Netherlands; Department of Neurosurgery (A.I.R.M.), Antwerp University Hospital, Edegem; and Department of Translational Neuroscience (A.I.R.M.), Faculty of Medicine and Health Science, University of Antwerp, Belgium.ORCID 0000-0002-2190-9278
Kevin K W WangFrom the Perioperative, Acute, Critical Care and Emergency Medicine (PACE) (D.P.W., D.M., V.F.J.N.), Department of Medicine, University of Cambridge, Addenbrooke's Hospital; Division of Psychology (L.W.), University of Stirling, United Kingdom; Department of Neurosurgery (E.C.), Medical School, and Neurotrauma Research Group (E.C.), Szentagothai Research Centre, University of Pecs, Hungary; Department of Neurosurgery (A.B.), Faculty of Medicine and Health, Örebro University, Sweden; Department of Neurobiology (K.K.W.W.), Center for Neurotrauma, Multiomics & Biomarkers (CNMB) Neuroscience Institute, Morehouse School of Medicine (MSM), Atlanta, GA; Program for Neurotrauma, Neuroproteomics and Biomarker Research (K.K.W.W.), Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville; Institute of Psychology (N.v.S., M.Z.), University of Innsbruck; Faculty of Psychotherapy Science (M.Z.), Sigmund Freud University, Vienna, Austria; Department of Biomedical Data Sciences (E.S.), Leiden University Medical Center, the Netherlands; Department of Neurosurgery (A.I.R.M.), Antwerp University Hospital, Edegem; and Department of Translational Neuroscience (A.I.R.M.), Faculty of Medicine and Health Science, University of Antwerp, Belgium.ORCID 0000-0002-9343-6473
Nicole von SteinbüchelFrom the Perioperative, Acute, Critical Care and Emergency Medicine (PACE) (D.P.W., D.M., V.F.J.N.), Department of Medicine, University of Cambridge, Addenbrooke's Hospital; Division of Psychology (L.W.), University of Stirling, United Kingdom; Department of Neurosurgery (E.C.), Medical School, and Neurotrauma Research Group (E.C.), Szentagothai Research Centre, University of Pecs, Hungary; Department of Neurosurgery (A.B.), Faculty of Medicine and Health, Örebro University, Sweden; Department of Neurobiology (K.K.W.W.), Center for Neurotrauma, Multiomics & Biomarkers (CNMB) Neuroscience Institute, Morehouse School of Medicine (MSM), Atlanta, GA; Program for Neurotrauma, Neuroproteomics and Biomarker Research (K.K.W.W.), Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville; Institute of Psychology (N.v.S., M.Z.), University of Innsbruck; Faculty of Psychotherapy Science (M.Z.), Sigmund Freud University, Vienna, Austria; Department of Biomedical Data Sciences (E.S.), Leiden University Medical Center, the Netherlands; Department of Neurosurgery (A.I.R.M.), Antwerp University Hospital, Edegem; and Department of Translational Neuroscience (A.I.R.M.), Faculty of Medicine and Health Science, University of Antwerp, Belgium.ORCID 0000-0003-4143-4713
Marina ZeldovichFrom the Perioperative, Acute, Critical Care and Emergency Medicine (PACE) (D.P.W., D.M., V.F.J.N.), Department of Medicine, University of Cambridge, Addenbrooke's Hospital; Division of Psychology (L.W.), University of Stirling, United Kingdom; Department of Neurosurgery (E.C.), Medical School, and Neurotrauma Research Group (E.C.), Szentagothai Research Centre, University of Pecs, Hungary; Department of Neurosurgery (A.B.), Faculty of Medicine and Health, Örebro University, Sweden; Department of Neurobiology (K.K.W.W.), Center for Neurotrauma, Multiomics & Biomarkers (CNMB) Neuroscience Institute, Morehouse School of Medicine (MSM), Atlanta, GA; Program for Neurotrauma, Neuroproteomics and Biomarker Research (K.K.W.W.), Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville; Institute of Psychology (N.v.S., M.Z.), University of Innsbruck; Faculty of Psychotherapy Science (M.Z.), Sigmund Freud University, Vienna, Austria; Department of Biomedical Data Sciences (E.S.), Leiden University Medical Center, the Netherlands; Department of Neurosurgery (A.I.R.M.), Antwerp University Hospital, Edegem; and Department of Translational Neuroscience (A.I.R.M.), Faculty of Medicine and Health Science, University of Antwerp, Belgium.ORCID 0000-0003-0172-9904
Ewout SteyerbergFrom the Perioperative, Acute, Critical Care and Emergency Medicine (PACE) (D.P.W., D.M., V.F.J.N.), Department of Medicine, University of Cambridge, Addenbrooke's Hospital; Division of Psychology (L.W.), University of Stirling, United Kingdom; Department of Neurosurgery (E.C.), Medical School, and Neurotrauma Research Group (E.C.), Szentagothai Research Centre, University of Pecs, Hungary; Department of Neurosurgery (A.B.), Faculty of Medicine and Health, Örebro University, Sweden; Department of Neurobiology (K.K.W.W.), Center for Neurotrauma, Multiomics & Biomarkers (CNMB) Neuroscience Institute, Morehouse School of Medicine (MSM), Atlanta, GA; Program for Neurotrauma, Neuroproteomics and Biomarker Research (K.K.W.W.), Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville; Institute of Psychology (N.v.S., M.Z.), University of Innsbruck; Faculty of Psychotherapy Science (M.Z.), Sigmund Freud University, Vienna, Austria; Department of Biomedical Data Sciences (E.S.), Leiden University Medical Center, the Netherlands; Department of Neurosurgery (A.I.R.M.), Antwerp University Hospital, Edegem; and Department of Translational Neuroscience (A.I.R.M.), Faculty of Medicine and Health Science, University of Antwerp, Belgium.
Andrew I R MaasFrom the Perioperative, Acute, Critical Care and Emergency Medicine (PACE) (D.P.W., D.M., V.F.J.N.), Department of Medicine, University of Cambridge, Addenbrooke's Hospital; Division of Psychology (L.W.), University of Stirling, United Kingdom; Department of Neurosurgery (E.C.), Medical School, and Neurotrauma Research Group (E.C.), Szentagothai Research Centre, University of Pecs, Hungary; Department of Neurosurgery (A.B.), Faculty of Medicine and Health, Örebro University, Sweden; Department of Neurobiology (K.K.W.W.), Center for Neurotrauma, Multiomics & Biomarkers (CNMB) Neuroscience Institute, Morehouse School of Medicine (MSM), Atlanta, GA; Program for Neurotrauma, Neuroproteomics and Biomarker Research (K.K.W.W.), Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville; Institute of Psychology (N.v.S., M.Z.), University of Innsbruck; Faculty of Psychotherapy Science (M.Z.), Sigmund Freud University, Vienna, Austria; Department of Biomedical Data Sciences (E.S.), Leiden University Medical Center, the Netherlands; Department of Neurosurgery (A.I.R.M.), Antwerp University Hospital, Edegem; and Department of Translational Neuroscience (A.I.R.M.), Faculty of Medicine and Health Science, University of Antwerp, Belgium.ORCID 0000-0003-1612-1264
David K MenonFrom the Perioperative, Acute, Critical Care and Emergency Medicine (PACE) (D.P.W., D.M., V.F.J.N.), Department of Medicine, University of Cambridge, Addenbrooke's Hospital; Division of Psychology (L.W.), University of Stirling, United Kingdom; Department of Neurosurgery (E.C.), Medical School, and Neurotrauma Research Group (E.C.), Szentagothai Research Centre, University of Pecs, Hungary; Department of Neurosurgery (A.B.), Faculty of Medicine and Health, Örebro University, Sweden; Department of Neurobiology (K.K.W.W.), Center for Neurotrauma, Multiomics & Biomarkers (CNMB) Neuroscience Institute, Morehouse School of Medicine (MSM), Atlanta, GA; Program for Neurotrauma, Neuroproteomics and Biomarker Research (K.K.W.W.), Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville; Institute of Psychology (N.v.S., M.Z.), University of Innsbruck; Faculty of Psychotherapy Science (M.Z.), Sigmund Freud University, Vienna, Austria; Department of Biomedical Data Sciences (E.S.), Leiden University Medical Center, the Netherlands; Department of Neurosurgery (A.I.R.M.), Antwerp University Hospital, Edegem; and Department of Translational Neuroscience (A.I.R.M.), Faculty of Medicine and Health Science, University of Antwerp, Belgium.ORCID 0000-0002-3228-9692
Virginia F J NewcombeFrom the Perioperative, Acute, Critical Care and Emergency Medicine (PACE) (D.P.W., D.M., V.F.J.N.), Department of Medicine, University of Cambridge, Addenbrooke's Hospital; Division of Psychology (L.W.), University of Stirling, United Kingdom; Department of Neurosurgery (E.C.), Medical School, and Neurotrauma Research Group (E.C.), Szentagothai Research Centre, University of Pecs, Hungary; Department of Neurosurgery (A.B.), Faculty of Medicine and Health, Örebro University, Sweden; Department of Neurobiology (K.K.W.W.), Center for Neurotrauma, Multiomics & Biomarkers (CNMB) Neuroscience Institute, Morehouse School of Medicine (MSM), Atlanta, GA; Program for Neurotrauma, Neuroproteomics and Biomarker Research (K.K.W.W.), Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville; Institute of Psychology (N.v.S., M.Z.), University of Innsbruck; Faculty of Psychotherapy Science (M.Z.), Sigmund Freud University, Vienna, Austria; Department of Biomedical Data Sciences (E.S.), Leiden University Medical Center, the Netherlands; Department of Neurosurgery (A.I.R.M.), Antwerp University Hospital, Edegem; and Department of Translational Neuroscience (A.I.R.M.), Faculty of Medicine and Health Science, University of Antwerp, Belgium.ORCID 0000-0001-6044-9035
CENTER-TBI Investigators and ParticipantsFrom the Perioperative, Acute, Critical Care and Emergency Medicine (PACE) (D.P.W., D.M., V.F.J.N.), Department of Medicine, University of Cambridge, Addenbrooke's Hospital; Division of Psychology (L.W.), University of Stirling, United Kingdom; Department of Neurosurgery (E.C.), Medical School, and Neurotrauma Research Group (E.C.), Szentagothai Research Centre, University of Pecs, Hungary; Department of Neurosurgery (A.B.), Faculty of Medicine and Health, Örebro University, Sweden; Department of Neurobiology (K.K.W.W.), Center for Neurotrauma, Multiomics & Biomarkers (CNMB) Neuroscience Institute, Morehouse School of Medicine (MSM), Atlanta, GA; Program for Neurotrauma, Neuroproteomics and Biomarker Research (K.K.W.W.), Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville; Institute of Psychology (N.v.S., M.Z.), University of Innsbruck; Faculty of Psychotherapy Science (M.Z.), Sigmund Freud University, Vienna, Austria; Department of Biomedical Data Sciences (E.S.), Leiden University Medical Center, the Netherlands; Department of Neurosurgery (A.I.R.M.), Antwerp University Hospital, Edegem; and Department of Translational Neuroscience (A.I.R.M.), Faculty of Medicine and Health Science, University of Antwerp, Belgium.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesThere is seemingly contradictory evidence concerning relationships between day-of-injury biomarkers and outcomes after mild traumatic brain injury (mTBI). To address this issue, we examined the association between a panel of biomarkers and multidimensional TBI outcomes.
methodsParticipants with mTBI (Glasgow coma scores [GCSs] 13-15) were selected from Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury, a European observational study recruiting patients with TBI with indication for brain CT and presentation within 24 hours. Exclusion criteria for this secondary analysis were age younger than 16 years, incomplete biomarker panel, death, or no recorded outcomes. Participants were separated into 2 groups, CT-negative and CT-positive. Multivariable binary logistic regression was used to assess the relation between the log biomarker level (glial fibrillary acidic protein [GFAP], neurofilament light [NfL], neuron-specific enolase [NSE], S100 calcium-binding protein B [S100B], tau, ubiquitin C-terminal hydrolase L1 [UCH-L1]) and dichotomized 6-month outcomes (functional outcomes [GOSE score <8], health-related quality of life [HRQoL; Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS) score <52, Short-Form 12-Item Survey version 2 Mental Component Summary (SF12v2 MCS) score <40, Short-Form 12-Item Survey version 2 Physical Component Summary (SF12v2 PCS) score <40], persistent postconcussion symptoms [Rivermead Post-Concussion Symptoms Questionnaire score ≥16], anxiety disorder [Generalized Anxiety Disorder-7 (GAD-7) score ≥8], depression [Patient Health Questionnaire-9 (PHQ-9) score ≥10], and post-traumatic stress disorder [PTSD Checklist for DSM-5 (PCL-5) score ≥33]).
resultsA total of 1,589 participants (865 CT-negative, 724 CT-positive) were included (77% GCS 15, median age 52 years, 66% male). Higher biomarker levels were associated with a GOSE score <8: CT-negative: S100B (odds ratio [OR] 1.78, 95% CI 1.43-2.23) and UCH-L1 (OR 1.16, 95% CI 1.01-1.33); CT-positive: GFAP (OR 1.22, 95% CI 1.11-1.36), NfL (OR 1.30, 95% CI 1.11-1.52), S100B (OR 1.51, 95% CI 1.23-1.86), tau (OR 1.36, 95% CI 1.17-1.59), and UCH-L1 (OR 1.34, 95% CI 1.17-1.53). In CT-positive participants, positive association was seen between NfL (OR 1.3, 95% CI 1.06-1.60) and UCH-L1 (OR 1.28, 95% CI 1.07-1.54) with QOLIBRI-OS; S100B (OR 1.32, 95% CI 1.02-1.70) with SF12v2 PCS; and NSE (OR 1.52, 95% CI 1.06-2.18) and UCH-L1 (OR 1.21, 95% CI 1.01-1.46) with the GAD-7. However, in CT-negative participants only, negative associations were seen between GFAP and impairment on the QOLIBRI-OS (OR 0.76, 95% CI 0.66-0.88), SF12v2 MCS (OR 0.71, 95% CI 0.61-0.82), SF12v2 PCS (OR 0.79, 95% CI 0.68-0.91), GAD-7 (OR 0.80, 0.68-0.95), PHQ-9 (OR 0.80, 95% CI 0.68-0.93), and PCL-5 (OR 0.80, 95% CI 0.66-0.97). DISCUSSION: Participants with higher biomarker levels had greater odds of impaired functional recovery. However, in CT-negative participants, higher GFAP concentrations were associated with better HRQoL and less impaired mental health. Further exploration is required of the patient phenotypes that may explain the relationships observed in this analysis.
Indexed as
BiomarkersBrain ConcussionPatient Reported Outcome MeasuresAdultAgedFemaleGlasgow Coma ScaleGlial Fibrillary Acidic ProteinHumansMaleMiddle AgedNeurofilament ProteinsPhosphopyruvate HydrataseS100 Calcium Binding Protein beta Subunittau ProteinsUbiquitin ThiolesteraseBiomarkersGFAP protein, humanGlial Fibrillary Acidic ProteinMAPT protein, humanneurofilament protein LNeurofilament ProteinsPhosphopyruvate HydrataseS100B protein, humanS100 Calcium Binding Protein beta Subunittau ProteinsUbiquitin ThiolesteraseUCHL1 protein, human
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