Glial Fibrillary Acidic Protein (GFAP) Outperforms S100 Calcium-Binding Protein B (S100B) and Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) as Predictor for Positive Computed Tomography of the Head in Trauma Subjects.

OBJECTIVE: Traumatic brain injuries (TBIs) are largely underdiagnosed and may have persistent refractory consequences. Current assessments for acute TBI are limited to physical examination and imaging. Biomarkers such as glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and S100 calcium-binding protein B (S100B) have shown predictive value as indicators of TBI and potential screening tools. METHODS: In total, 37 controls and 118 unique trauma subjects who received a clinically ordered head computed tomography (CT) in the emergency department of a level 1 trauma center were evaluated. Blood samples collected at 0-8 hours (initial) and 12-32 hours (delayed) postinjury were analyzed for GFAP, UCH-L1, and S100B concentrations. These were then compared in CT-negative and CT-positive subjects. RESULTS: Median GFAP, UCH-L1, and S100B concentrations were greater in CT-positive subjects at both timepoints compared with CT-negative subjects. In addition, median UCH-L1 and S100B concentrations were lower at the delayed timepoint, whereas median GFAP concentrations were increased. As predictors of a positive CT of the head, GFAP outperformed UCH-L1 and S100B at both timepoints (initial: 0.89 sensitivity, 0.62 specificity; delayed: 0.94 sensitivity, 0.67 specificity). GFAP alone also outperformed all possible combinations of biomarkers. CONCLUSIONS: GFAP, UCH-L1, and S100B demonstrated utility for rapid prediction of a CT-positive TBI within 0-8 hours of injury. GFAP exhibited the greatest predictive power at 12-32 hours. Furthermore, these results suggest that GFAP alone has greater utility for predicting a positive CT of the head than UCH-L1, S100B, or any combination of the 3.

Hyperbaric Oxygen Therapy in the Treatment of Acute Severe Traumatic Brain Injury: A Systematic Review.

There has been no major advancement in a quarter of a century for the treatment of acute severe traumatic brain injury (TBI). This review summarizes 40 years of clinical and pre-clinical research on the treatment of acute TBI with hyperbaric oxygen therapy (HBO2) in the context of an impending National Institute of Neurologic Disorders and Stroke-funded, multi-center, randomized, adaptive Phase II clinical trial -the Hyperbaric Oxygen Brain Injury Treatment (HOBIT) trial. Thirty studies (eight clinical and 22 pre-clinical) that administered HBO2 within 30 days of a TBI were identified from PubMed searches. The pre-clinical studies consistently reported positive treatment effects across a variety of outcome measures with almost no safety concerns, thus providing strong proof-of-concept evidence for treating severe TBI in the acute setting. Of the eight clinical studies reviewed, four were based on the senior author's (GR) investigation of HBO2 as a treatment for acute severe TBI. These studies provided evidence that HBO2 significantly improves physiologic measures without causing cerebral or pulmonary toxicity and can potentially improve clinical outcome. These results were consistent across the other four reviewed clinical studies, thus providing preliminary clinical data supporting the HOBIT trial. This comprehensive review demonstrates that HBO2 has the potential to be the first significant treatment in the acute phase of severe TBI.