Effects of Selective Head-and-Neck Cooling on Brain Injury-Related Biomarker Levels and Symptom Rating Following a Boxing Bout: Protocol for an Exploratory Randomized Trial
Bibliographic record
Abstract
BACKGROUND: Head impacts are common in contact sports such as boxing and occur at times of elevated core body and brain temperatures induced by the exercise. Following impact, elevated brain temperature may lead to the development of exacerbated brain injury that can be monitored by blood biomarkers. Blood-brain biomarkers S100B and glial fibrillary acidic protein (GFAP) reflect glial injury; neurofilament light (NFL), axonal injury; and Neuron-Specific Enolase (NSE) and Tubulin-associated unit (tau), neuronal injury. Time to peak levels post injury for these biomarkers varies. Levels of S100B l peak early post injury, while NSE, GFAP, and tau are regarded as subacute markers, and NFL shows prolonged increases. We attempt to cover a large spectrum of first week postfight alterations in blood-brain biomarkers and their response to head-neck cooling. OBJECTIVE: We hypothesized that acute head-and-neck cooling, recently shown to shorten return-to-play in concussed ice hockey players, applied acutely following a boxing bout, is associated with an attenuated concentration of blood biomarkers and improved symptom rating. METHODS: The trial is academically driven and funded by external and hospital research funds. Young, healthy elite boxers aged ≥18 years are recruited. Before, and immediately after a competitive boxing bout consisting of 2 or 3 rounds of 2 minutes each, blood samples are drawn. Boxers are randomized to intervention or control management by 1:1 allocation before baseline testing. After the initial postfight blood sample is drawn and symptom rating using the Sports Concussion Assessment Tool-5 (SCAT-5) has been collected, the boxers receive either acute selective head-and-neck cooling for 45 minutes or routine postfight management. The number of head impacts is counted in all boxers on match video recordings. In both groups, blood samples are drawn 45 minutes after the initial postbout blood sample, as well as 3 and 6 days post fight. At all blood sampling time points, the number of symptoms (NOS) and symptom severity score (SSS) are assessed using the symptom rating part of the SCAT-5. The primary endpoint is the difference in biomarker levels (GFAP, NFL, tau, UCH-L1, neuronal-specific enolase) immediately post fight and preintervention, to those obtained at 6 days post fight. The postfight SCAT-5 NOS and SSS are secondary endpoints. RESULTS: Recruitment started in November 2021 and is ongoing. So far, 41 boxers have been included: 20 controls and 21 cooled. Data collection started in October 2024 following the completion of blood sample analysis. We expect to recruit more boxers before the middle of 2025, but challenges with recruitment may limit this. CONCLUSIONS: There is no treatment available for boxing-induced brain injury. Biomarkers are surrogate yet objective markers of brain injury, and the head-and-neck cooling treatment may attenuate the concentration of brain injury-related biomarkers as well as reduce symptoms induced by head impacts attained during a boxing fight. TRIAL REGISTRATION: ClinicalTrials.gov NCT06386484; https://clinicaltrials.gov/study/NCT06386484. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/68954.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.012 | 0.012 |
| Meta-epidemiology (narrow) | 0.006 | 0.002 |
| Meta-epidemiology (broad) | 0.011 | 0.004 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.002 | 0.003 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.006 | 0.006 |
| Insufficient payload (model declined to judge) | 0.045 | 0.008 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".