Military Medicine | July 7, 2026 | Commentary

Making the Invisible Wounds of War Visible

Brian L. Edlow, MD; VADM (Ret) Timothy G. Szymanski; CMSgt (Ret) Gregory A. Smith; HON (Ret) Frank J. Larkin; James P. Kelly, MA, MD; Daniel P. Perl, MD

This commentary explores the current state of the science in military brain injury and proposes that the development of new diagnostic tests is essential to optimize military brain health care. The authors advocate for a comprehensive, multidisciplinary effort to identify advanced neurotechnologies that detect the “invisible wounds of war.” Co-authored by Oragenics Chief Medical Officer Dr. James P. Kelly.

View Publication DOI: 10.1093/milmed/usag279

Academic Emergency Medicine | April 2026 | Original Research

Age-Specific Clinical Biomarker Ranges in Acute Head Injury, Non-TBI Trauma, and Healthy Control Subjects in the Emergency Department

Katherine D. Mayes, MD; Timothy E. Van Meter, PhD; Nazanin Mirshahi; Sally Boyd; Danielle Sandsmark, MD, PhD; Katya Rascovsky, PhD; Ramon Diaz-Arrastia, MD, PhD; Justin Weppner, DO; W. Frank Peacock, MD; Damon R. Kuehl, MD; the HeadSMART II Investigators

Serum samples from 762 emergency department patients — healthy controls, non-head trauma controls, and mild TBI patients — were analyzed across six candidate brain injury biomarkers to separate the influence of normal aging from the influence of injury. For several markers, most notably GFAP and von Willebrand factor, the variation attributable to age matched or exceeded the variation attributable to head injury itself. The authors conclude that diagnostic algorithms built without age-normalized reference ranges risk misclassifying patients, particularly older adults.

View Publication DOI: 10.1111/acem.70298

Diagnostics | January 27, 2026 | Original Research

The Use of Digital Neurocognitive Assessments to Assess Traumatic Brain Injury and Dementia in Older Trauma Patients: An Emergency Department Feasibility Study

Justin Weppner, DO, MEd; Justin Gray; Damon Kuehl, MD; Danielle Sandsmark, MD, PhD; Nazanin Mirshahi, PhD; Ramon Diaz-Arrastia, MD, PhD; Katya Rascovsky, PhD; W. Frank Peacock, MD; Timothy E. Van Meter, PhD

Older adults account for a disproportionate share of TBI hospitalizations and deaths, yet remain among the least studied groups in brain injury research. This feasibility study tested a tablet-based cognitive battery in 101 mild TBI patients and 52 orthopedic trauma controls aged 65 and older across 14 U.S. trauma centers. The tool reliably identified cognitive impairment and worked regardless of how comfortable participants were with tablets — but it could not separate injury-related deficits from pre-existing dementia, pointing toward the need to pair cognitive testing with blood-based biomarkers.

View Publication DOI: 10.3390/diagnostics16030400

American Journal of Emergency Medicine | November 2024 | Systematic Review & Meta-Analysis

Neurogranin as a Biomarker in Differentiating Traumatic Brain Injury: A Systematic Review and Meta-Analysis

W. Frank Peacock, MD; Krzysztof Kurek; Michal Pruc; Zubaid Rafique, MD; Lukasz Szarpak, PhD

Neurogranin is a synaptic protein largely confined to the brain, which makes it an appealing candidate for a blood test that can confirm injury when imaging cannot. Screening 172 published articles down to four that met quality criteria, this meta-analysis pooled 451 TBI patients against 522 controls and found neurogranin levels significantly higher after injury (standardized mean difference 1.00; 95% CI 0.19–1.81; p = 0.02). The authors note substantial variability between the studies and differences in how long after injury blood was drawn, and conclude that neurogranin is promising for both detection and severity classification while the size of the clinical effect remains to be established. One of the four qualifying studies was the 2017 three-biomarker panel derivation listed below.

View Publication DOI: 10.1016/j.ajem.2024.07.005

The Journal of Applied Laboratory Medicine | September 3, 2024 | Special Report

On-Field Rule Out of Mild Traumatic Brain Injury: Can Blood-Based Biomarker Testing Change Outcome of Major Sporting Events?

Alan H.B. Wu, PhD; W. Franklin Peacock, MD

Return-to-play decisions in professional sport are still made on subjective assessment, and no laboratory test is approved for ruling out concussion at the sideline. This report proposes a different way to read the same blood markers: instead of comparing a result against a population reference range, compare it against a baseline drawn from that same athlete before competition. Markers whose levels stay steady within an individual while healthy — including GFAP, fatty acid binding protein 7, and astrocytic phosphoprotein — are the strongest candidates, with a documented reference change value for GFAP of 37%. The authors argue the same approach could extend to military personnel and other occupations at high risk of head injury, and outline the validation work required first.

View Publication DOI: 10.1093/jalm/jfae070

Psychological Medicine | July 2022 | Original Article

Socio-Demographic and Trauma-Related Predictors of Depression Within Eight Weeks of Motor Vehicle Collision in the AURORA Study

Jutta Joormann, PhD; Samuel A. McLean, MD, MPH; Francesca L. Beaudoin, MD, PhD; Xinming An, PhD; Jennifer S. Stevens, PhD; Donglin Zeng, PhD; Thomas C. Neylan, MD; W. Frank Peacock, MD; Karestan C. Koenen, PhD; Kerry J. Ressler, MD, PhD; Ronald C. Kessler, PhD; and the AURORA Study Investigators

Head injury is only one of the adverse outcomes that follows a motor vehicle collision. This first depression report from the NIMH-funded AURORA study followed 666 patients enrolled within 72 hours of a collision across 23 U.S. emergency departments, and found that 27% met the threshold for moderate to severe depression eight weeks later. What predicted lasting depression was not the severity of a patient’s own injuries but the circumstances of the crash — riding as a passenger rather than driving carried nearly three times the odds, as did injuries to others in the vehicle. Personal injury characteristics, including head injury, predicted symptoms at two weeks but not beyond, pointing to different mechanisms behind early and persistent distress.

View Publication DOI: 10.1017/S0033291720003773

Frontiers in Neurology | December 8, 2021 | Study Protocol

Defining Acute Traumatic Encephalopathy: Methods of the “HEAD Injury Serum Markers and Multi-Modalities for Assessing Response to Trauma” (HeadSMART II) Study

W. Frank Peacock, MD; Damon Kuehl, MD; Jeff Bazarian, MD; Adam J. Singer, MD; Chad Cannon, MD; Zubaid Rafique, MD; James P. d’Etienne, MD; Robert Welch, MD; Carol Clark, MD; Ramon Diaz-Arrastia, MD, PhD

This protocol paper lays out the design of HeadSMART II, a multicenter observational study developing an objective, in-vitro diagnostic approach to acute traumatic encephalopathy. Because TBI remains a largely syndromic diagnosis based on reported loss of consciousness, amnesia, or confusion, the study combines blood protein biomarkers with digitized neurocognitive testing and clinical assessment to both identify brain-injured patients and estimate their risk of persistent post-concussive symptoms at 14, 30, and 90 days.

View Publication DOI: 10.3389/fneur.2021.733712

Academic Emergency Medicine | December 2019 | Research Letter

Clinical Gestalt for Early Prediction of Delayed Functional and Symptomatic Recovery From Mild Traumatic Brain Injury Is Inadequate

Frederick K. Korley, MD, PhD; W. Frank Peacock, MD; James T. Eckner, MD; Ronald Maio, DO, MS; Scott Levin, PhD; Kathleen T. Bechtold, PhD; Matthew Peters, MD; Durga Roy, MD; Hayley J. Falk, ScM; Anna J. Hall; Timothy E. Van Meter, PhD; Richard Gonzalez, PhD; Ramon Diaz-Arrastia, MD, PhD

Emergency clinicians treating 217 mild TBI patients were asked, on the day of injury, to predict which of them would still be impaired three months later. Their predictions performed at close to chance, and accuracy did not improve with years of clinical experience — even among clinicians who rated themselves highly certain. The findings underscore why objective, data-driven tools are needed for risk stratification in acute care settings.

View Publication DOI: 10.1111/acem.13844

Frontiers in Neurology | November 30, 2017 | Original Research

Derivation of a Three Biomarker Panel to Improve Diagnosis in Patients with Mild Traumatic Brain Injury

W. Frank Peacock IV, MD; Timothy E. Van Meter, PhD; Nazanin Mirshahi; Kyle Ferber; Robert Gerwien, PhD; Vani Rao, MD; Haris Iqbal Sair, MD; Ramon Diaz-Arrastia, MD, PhD; Frederick K. Korley, MD, PhD

More than 90% of head-injured patients who receive a CT scan show no anatomic abnormality, leaving a large group whose injury is real but invisible to imaging. Using 662 patients from the original HeadSMART cohort, this study built a serum panel combining neurogranin, neuron-specific enolase, and metallothionein 3 with age and sex, and correctly classified mild TBI in roughly three-quarters of CT-negative patients. Samples drawn within two hours of injury classified correctly in every case tested, suggesting the markers are detectable in the hyperacute window.

View Publication DOI: 10.3389/fneur.2017.00641

PLOS ONE | July 7, 2017 | Research Article

Diagnostic Accuracy of Tablet-Based Software for the Detection of Concussion

Suosuo Yang; Benjamin Flores; Rotem Magal; Kyrsti Harris; Jonathan Gross; Amy Ewbank; Sasha Davenport; Pablo Ormachea; Waleed Nasser; Weidong Le, MD, PhD; W. Frank Peacock, MD; Yael Katz, PhD; David M. Eagleman, PhD

This study evaluated a six-test tablet battery — covering attention, processing speed, executive function, memory, and balance — against physician diagnosis in 30 emergency department concussion patients, 30 pain-matched controls, and 538 healthy participants. A composite score built from the six assessments separated injured from uninjured individuals with 83% sensitivity and 87% specificity, and the full battery took most users under five minutes. A hidden module was included to flag deliberate underperformance.

View Publication DOI: 10.1371/journal.pone.0179352

Journal of Neurotrauma | April 15, 2017 | Letter to the Editor

Controls Can’t Be Ignored

W. Frank Peacock, MD

A letter arguing that biomarker discovery studies live or die on how precisely the control population is defined. Reviewing a published mild TBI biomarker panel, the author notes that the control group was characterized only in the broadest terms, and that the copeptin concentrations implied by the study’s own figures fall in a range previously associated with elevated short-term mortality risk — raising the question of whether that cohort can meaningfully serve as a control at all.

View Publication DOI: 10.1089/neu.2016.4664