Genetic Variants and Hamstring Injury in Soccer: An Association and Validation Study.

PURPOSE: This study aimed to investigate the association of candidate single nucleotide polymorphisms (SNP) with noncontact hamstring muscle injuries in elite soccer players and to create and validate a model to assess the risk of hamstring injury. METHODS: A total of 107 elite male outfield players were prospectively followed for six seasons. Players were genotyped for 37 SNP previously investigated in relation to musculoskeletal injuries. The association of SNP, previous injury, age, level of play, position, and anthropometric data with 129 hamstring injuries (413 observations) was investigated in the discovery phase (2010-2015), and a multivariable Cox frailty model was created using forward selection. The model's discriminative ability was tested in the validation phase (2015-2016, 31 injuries, 98 observations) using Harrell's C index. RESULTS: Five SNP were found to be significantly associated with hamstring injury in a multivariable model: matrix metalloproteinase 3 rs679620 (A vs G, hazard ratio [HR] = 2.06, 95% confidence interval [CI] = 1.51-2.81), tenascin C rs2104772 (A vs T, HR = 1.65, 95% CI = 1.17-2.32), interleukin 6 rs1800795 (GG vs GC + CC, HR = 1.68, 95% CI = 1.11-2.53), nitric oxide synthase 3 rs1799983 (G vs T, HR = 1.35, 95% CI = 1.01-1.79), and hypoxia-inducible factor-1α rs11549465 (CC vs CT, HR = 2.08, 95% CI = 1.00-4.29). Age also entered the model (≥24 vs <24 yr, HR = 2.10, 95% CI = 1.29-3.42). The model showed acceptable discrimination in the discovery phase (C index = 0.74), but not in the validation phase (C index = 0.52). CONCLUSION: Genetic variants appear to be involved in the etiology of hamstring injuries but were not found to have predictive value by themselves. Further research, increasing the number of genetic variants and including environmental factors in complex multifactorial risk models, is necessary.

Inflammatory biomarkers in combat wound healing.

BACKGROUND: Modern war ballistics and blast injuries inflict devastating extremity injuries, violating soft tissue, bone, and neurovascular structures. Despite advances in complex wound management, appropriate timing of war wound closure remains subjective. In addition, the pathophysiology of acute wound failure is poorly defined. METHODS: Patients with penetrating extremity wounds sustained during combat were prospectively studied and followed for 30 days after definitive wound closure. The primary outcome was wound healing. Wound dehiscence was defined as spontaneous partial or complete wound disruption after closure. Serum, wound effluent, and wound bed tissue biopsy were collected at each surgical wound debridement. Serum and wound effluent were analyzed with a multiplex array of 22 cytokines and chemokines, and wound tissue for corresponding gene transcript expression. RESULTS: Fifty-two penetrating extremity war wounds in 33 male patients were investigated. Nine (17%) wounds dehisced. Concomitant vascular injury, increased wound size, and higher injury severity score correlated with wound dehiscence. Both serum and wound effluent cytokine and chemokine protein profiles were statistically associated with healing outcome at various time points. Wound biopsy gene transcript expression demonstrated increased tissue inflammation associated with wound failure. Multiple protein and gene transcript biomarkers predictive of wound healing were identified. CONCLUSIONS: The cytokine and chemokine protein and gene transcript expression patterns demonstrate a condition of inflammatory dysregulation associated with war wound failure. A molecular biomarker panel may predict combat wound healing outcome and warrants prospective validation.