The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury

Matthew K Bagg^{1

2

3

4}, Sarah C Hellewell^{1

2

5}, Jemma Keeves^{1

2

6}, Ana Antonic-Baker⁷, Ancelin McKimmie⁶, Amelia J Hicks^{8

9}, Adelle Gadowski⁶, Virginia F J Newcombe¹⁰, Karen M Barlow^{11

12}, Zsolt J Balogh¹³, Jason P Ross¹⁴, Meng Law^{15

16

17}, Karen Caeyenberghs¹⁸, Paul M Parizel^{19

20

21}, Jacinta Thorne^{1

2}, Melissa Papini^{1

2}, Geena Gill^{1

2}, Amanda Jefferson^{1

2}, Jennie L Ponsford^{8

9}, Natasha A Lannin^{7

22}, Terence J O'Brien⁷, Peter A Cameron^{6

23

24}, D Jamie Cooper^{25

26}, Nick Rushworth²⁷, Belinda J Gabbe^{6

28}, Melinda Fitzgerald^{1

2}

Affiliations

¹ Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia.
² Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia.
³ Centre for Pain IMPACT, Neuroscience Research Australia, Sydney, NSW, Australia.
⁴ School of Health Sciences, University of Notre Dame Australia, Fremantle, WA, Australia.
⁵ School of Medicine, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia.
⁶ School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁷ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia.
⁸ Monash-Epworth Rehabilitation Research Centre, Epworth Healthcare, Melbourne, VIC, Australia.
⁹ School of Psychological Sciences, Monash University, Melbourne, VIC, Australia.
¹⁰ PACE Section, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
¹¹ Acquired Brain Injury in Children Research Program, Queensland Children's Hospital, Brisbane, QLD, Australia.
¹² Centre for Children's Health Research, University of Queensland, Brisbane, QLD, Australia.
¹³ Department of Traumatology, John Hunter Hospital and University of Newcastle, Newcastle, NSW, Australia.
¹⁴ Molecular Diagnostic Solutions, Health and Biosecurity, CSIRO, Australia.
¹⁵ Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
¹⁶ Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
¹⁷ Department of Neuroscience and Radiology, Monash University, Alfred Health, Melbourne, VIC, Australia.
¹⁸ Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia.
¹⁹ University of Antwerp, Edegem, Belgium.
²⁰ Department of Radiology, Royal Perth Hospital and University of Western Australia, Perth, WA, Australia.
²¹ West Australian National Imaging Facility Node, Nedlands, WA, Australia.
²² Alfred Health, Melbourne, VIC, Australia.
²³ National Trauma Research Institute, Melbourne, VIC, Australia.
²⁴ Emergency and Trauma Centre, The Alfred Hospital, Melbourne, VIC, Australia.
²⁵ Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
²⁶ Department of Intensive Care and Hyperbaric Medicine, The Alfred, Melbourne, VIC, Australia.
²⁷ Brain Injury Australia, Sydney, NSW, Australia.
²⁸ Health Data Research UK, Swansea University Medical School, Swansea University, Singleton Park, United Kingdom.

PMID: 38115587
DOI: 10.1089/neu.2023.0464

Review

The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury

Matthew K Bagg et al. J Neurotrauma. 2025 Nov.

. 2025 Nov;42(21-22):2116-2137.

doi: 10.1089/neu.2023.0464. Epub 2024 Mar 8.

Authors

Affiliations

¹ Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia.
² Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia.
³ Centre for Pain IMPACT, Neuroscience Research Australia, Sydney, NSW, Australia.
⁴ School of Health Sciences, University of Notre Dame Australia, Fremantle, WA, Australia.
⁵ School of Medicine, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia.
⁶ School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁷ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia.
⁸ Monash-Epworth Rehabilitation Research Centre, Epworth Healthcare, Melbourne, VIC, Australia.
⁹ School of Psychological Sciences, Monash University, Melbourne, VIC, Australia.
¹⁰ PACE Section, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
¹¹ Acquired Brain Injury in Children Research Program, Queensland Children's Hospital, Brisbane, QLD, Australia.
¹² Centre for Children's Health Research, University of Queensland, Brisbane, QLD, Australia.
¹³ Department of Traumatology, John Hunter Hospital and University of Newcastle, Newcastle, NSW, Australia.
¹⁴ Molecular Diagnostic Solutions, Health and Biosecurity, CSIRO, Australia.
¹⁵ Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
¹⁶ Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
¹⁷ Department of Neuroscience and Radiology, Monash University, Alfred Health, Melbourne, VIC, Australia.
¹⁸ Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia.
¹⁹ University of Antwerp, Edegem, Belgium.
²⁰ Department of Radiology, Royal Perth Hospital and University of Western Australia, Perth, WA, Australia.
²¹ West Australian National Imaging Facility Node, Nedlands, WA, Australia.
²² Alfred Health, Melbourne, VIC, Australia.
²³ National Trauma Research Institute, Melbourne, VIC, Australia.
²⁴ Emergency and Trauma Centre, The Alfred Hospital, Melbourne, VIC, Australia.
²⁵ Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
²⁶ Department of Intensive Care and Hyperbaric Medicine, The Alfred, Melbourne, VIC, Australia.
²⁷ Brain Injury Australia, Sydney, NSW, Australia.
²⁸ Health Data Research UK, Swansea University Medical School, Swansea University, Singleton Park, United Kingdom.

PMID: 38115587
DOI: 10.1089/neu.2023.0464

Abstract

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.

Keywords: biomarkers; body fluids; brain injuries, traumatic; common data elements; magnetic resonance imaging; systematic review [publication type]; tissues; tomography, X-ray computed.

PubMed Disclaimer

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

LinkOut - more resources

Full Text Sources
- Atypon
Medical
- 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

The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury

Affiliations

The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous