Blood-Based Protein Biomarkers for the Management of Traumatic Brain Injuries in Adults Presenting with Mild Head Injury to Emergency Departments : A Living Systematic Review and Meta-Analysis

Accurate diagnosis of traumatic brain injury (TBI) is critical to effective management and intervention, but can be challenging in patients with mild TBI. A substantial number of studies have reported the use of circulating biomarkers as signatures for TBI, capable of improving diagnostic accuracy and clinical decision-making beyond current practice standards. We performed a systematic review and meta-analysis to comprehensively and critically evaluate the existing body of evidence for the use of blood protein biomarkers (S100B, GFAP, NSE, UCH-L1, Tau and Neurofilament proteins) for diagnosis of intracranial lesions on CT following mild TBI. Effects of potential confounding factors and differential diagnostic performance of the included markers were explored. Furthermore, appropriateness of study design, analysis, quality and demonstration of clinical utility were assessed. Studies published up to October 2016 were identified through a MEDLINE, EMBASE and CINHAL search. Following screening of the identified articles, 26 were selected as relevant. We found that measurement of S100B can help informed decision making in the emergency department possibly reducing resource use, but there is insufficient evidence that any of the other markers is ready for clinical application. Our work pointed out serious problems in the design, analysis and reporting of many of the studies and identi fi ed a substantial heterogeneity and research gaps. These findings emphasize the importance of methodologically rigorous studies focused on a biomarker's intended use and defining standardized, validated and reproducible approaches. The living nature of this systematic review, which will summarize key updated information as it becomes available, can inform and guide future implementation of biomarkers in the clinical arena.