Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury (CENTER-TBI): an observational cohort study

Isabel R A Retel Helmrich¹, Endre Czeiter², Krisztina Amrein², András Büki³, Hester F Lingsma¹, David K Menon⁴, Stefania Mondello⁵, Ewout W Steyerberg⁶, Nicole von Steinbüchel⁷, Kevin K W Wang⁸, Lindsay Wilson⁹, Haiyan Xu¹⁰, Zhihui Yang¹⁰, David van Klaveren¹¹, Andrew I R Maas¹²; CENTER-TBI participants and investigators

Affiliations

¹ Center for Medical Decision Making, Department of Public Health, Erasmus University Medical Center, Rotterdam, Netherlands.
² Department of Neurosurgery, Medical School, and Neurotrauma Research Group, Szentágothai Research Centre, University of Pécs, Pécs, Hungary; MTA-PTE Clinical Neuroscience MR Research Group, Pécs, Hungary.
³ Department of Neurosurgery, Medical School, and Neurotrauma Research Group, Szentágothai Research Centre, University of Pécs, Pécs, Hungary; Department of Neurosurgery Faculty of Medicine and Health Örebro University, Örebro, Sweden.
⁴ Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
⁵ Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
⁶ Center for Medical Decision Making, Department of Public Health, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands.
⁷ Institute of Medical Psychology and Medical Sociology, Universitätsmedizin Göttingen, Göttingen, Germany.
⁸ Program for Neurotrauma, Neuroproteomics and Biomarker Research, Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville, FL, USA; Brain Rehabilitation Research Center, Malcom Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
⁹ Division of Psychology, University of Stirling, Stirling, UK.
¹⁰ Program for Neurotrauma, Neuroproteomics and Biomarker Research, Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville, FL, USA.
¹¹ Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies/Tufts Medical Center, Boston, MA, USA.
¹² Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium. Electronic address: andrew.maas@uza.be.

PMID: 35963262
DOI: 10.1016/S1474-4422(22)00218-6

Observational Study

Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury (CENTER-TBI): an observational cohort study

Isabel R A Retel Helmrich et al. Lancet Neurol. 2022 Sep.

. 2022 Sep;21(9):792-802.

doi: 10.1016/S1474-4422(22)00218-6.

Authors

Affiliations

¹ Center for Medical Decision Making, Department of Public Health, Erasmus University Medical Center, Rotterdam, Netherlands.
² Department of Neurosurgery, Medical School, and Neurotrauma Research Group, Szentágothai Research Centre, University of Pécs, Pécs, Hungary; MTA-PTE Clinical Neuroscience MR Research Group, Pécs, Hungary.
³ Department of Neurosurgery, Medical School, and Neurotrauma Research Group, Szentágothai Research Centre, University of Pécs, Pécs, Hungary; Department of Neurosurgery Faculty of Medicine and Health Örebro University, Örebro, Sweden.
⁴ Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
⁵ Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
⁶ Center for Medical Decision Making, Department of Public Health, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands.
⁷ Institute of Medical Psychology and Medical Sociology, Universitätsmedizin Göttingen, Göttingen, Germany.
⁸ Program for Neurotrauma, Neuroproteomics and Biomarker Research, Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville, FL, USA; Brain Rehabilitation Research Center, Malcom Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
⁹ Division of Psychology, University of Stirling, Stirling, UK.
¹⁰ Program for Neurotrauma, Neuroproteomics and Biomarker Research, Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville, FL, USA.
¹¹ Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies/Tufts Medical Center, Boston, MA, USA.
¹² Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium. Electronic address: andrew.maas@uza.be.

PMID: 35963262
DOI: 10.1016/S1474-4422(22)00218-6

Abstract

Background: Several studies have reported an association between serum biomarker values and functional outcome following traumatic brain injury. We aimed to examine the incremental (added) prognostic value of serum biomarkers over demographic, clinical, and radiological characteristics and over established prognostic models, such as IMPACT and CRASH, for prediction of functional outcome.

Methods: We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study. We included patients aged 14 years or older who had blood sampling within 24 h of injury, results from a CT scan, and outcome assessment according to the Glasgow Outcome Scale-Extended (GOSE) at 6 months. Amounts in serum of six biomarkers (S100 calcium-binding protein B, neuron-specific enolase, glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1 [UCH-L1], neurofilament protein-light, and total tau) were measured. The incremental prognostic value of these biomarkers was determined separately and in combination. The primary outcome was the GOSE 6 months after injury. Incremental prognostic value, using proportional odds and a dichotomised analysis, was assessed by delta C-statistic and delta R² between models with and without serum biomarkers, corrected for optimism with a bootstrapping procedure.

Findings: Serum biomarker values and 6-month GOSE were available for 2283 of 4509 patients. Higher biomarker levels were associated with worse outcome. Adding biomarkers improved the C-statistic by 0·014 (95% CI 0·009-0·020) and R² by 4·9% (3·6-6·5) for predicting GOSE compared with demographic, clinical, and radiological characteristics. UCH-L1 had the greatest incremental prognostic value. Adding biomarkers to established prognostic models resulted in a relative increase in R² of 48-65% for IMPACT and 30-34% for CRASH prognostic models.

Interpretation: Serum biomarkers have incremental prognostic value for functional outcome after traumatic brain injury. Our findings support integration of biomarkers-particularly UCH-L1-in established prognostic models.

Funding: European Union's Seventh Framework Programme, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences, and NeuroTrauma Sciences.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests All authors were supported by grants from the EU, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences, and NeuroTrauma Sciences during the conduct of the study. DKM reports grants and personal fees from Lantmannen AB, Neurotrauma Sciences, Pressura Neuro, Calico, GlaxoSmithKline, Pfizer, Cortirio, ABCDx, Integra Neurosciences, Gryphon, and Pinteon, outside of the submitted work. AIRM declares personal fees from Abbott Laboratories and Novartis and participated on an advisory board from PresSura Neuro during the conduct of the study. EWS reports royalties for a textbook on clinical prediction models from Springer during the conduct of the study. KKWW reports being shareholder of Gryphon Bio during the conduct of the study. LW reports personal fees from Vasopharm, Roche Pharma, and Novartis during the conduct of the study.

Comment in

Biomarkers add value to traumatic brain injury prognosis.
McDonald SJ, O'Brien TJ, Shultz SR. McDonald SJ, et al. Lancet Neurol. 2022 Sep;21(9):761-763. doi: 10.1016/S1474-4422(22)00306-4. Lancet Neurol. 2022. PMID: 35963248 No abstract available.

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

LinkOut - more resources

Full Text Sources
- ClinicalKey
- Elsevier Science
Medical
- ClinicalTrials.gov
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury (CENTER-TBI): an observational cohort study

Affiliations

Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury (CENTER-TBI): an observational cohort study

Authors

Affiliations

Abstract

Conflict of interest statement

Comment in

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous