Nowak A, Kennelley G, Hager N, Metzger E, Isaacson B, hoenig T, Hollander K, Tenforde A

We enjoyed reading the articles by Abbott, et al. that cover the important topic of stress fractures in female military personnel “Part I: Background and Clinical Considerations for Stress Fractures in Female Military Recruits” and “Part II: Risk Factors for Stress Fractures in Female Military Recruits.” Both reviews identify that female military personnel are at a greater risk for stress fractures during training than their male counterparts and detail unique risk factors that are a necessary consideration in optimizing management. While we congratulate the authors for this detailed work, it is important to highlight additional research that adds to our understanding of this injury and the approach for management and prevention of these injuries.

Andrew S Nowak, Gabrielle E Kennelley, Nelson Hager, Elizabeth C Metzger, Brad Isaacson, Tim Hoenig, Karsten Hollander, Adam S Tenforde, Stress Fractures in the Military: Opportunities to Advance Recognition, Treatment, and Prevention, Military Medicine, Volume 188, Issue 9-10, September/October 2023, Pages 244–245, https://doi.org/10.1093/milmed/usad067

Negri LB, mannaa y, Korupolu S, farinelli w, anderson r, Gelfand J

Cutaneous bacterial wound infections typically involve gram-positive cocci such as Staphylococcus aureus (SA) and usually become biofilm infections. Bacteria in biofilms may be 100–1000-fold more resistant to an antibiotic than the clinical laboratory minimal inhibitory concentration (MIC) for that antibiotic, contributing to antimicrobial resistance (AMR). AMR is a growing global threat to humanity. One pathogen–antibiotic resistant combination, methicillin–resistant SA (MRSA) caused more deaths globally than any other such combination in a recent worldwide statistical review. Many wound infections are accessible to light. Antimicrobial phototherapy, and particularly antimicrobial blue light therapy (aBL) is an innovative non-antibiotic approach often overlooked as a possible alternative or adjunctive therapy to reduce antibiotic use. We therefore focused on aBL treatment of biofilm infections, especially MRSA, focusing on in vitro and ex vivo porcine skin models of bacterial biofilm infections. Since aBL is microbicidal through the generation of reactive oxygen species (ROS), we hypothesized that menadione (Vitamin K3), a multifunctional ROS generator, might enhance aBL. Our studies suggest that menadione can synergize with aBL to increase both ROS and microbicidal effects, acting as a photosensitizer as well as an ROS recycler in the treatment of biofilm infections. Vitamin K3/menadione has been given orally and intravenously worldwide to thousands of patients. We conclude that menadione/Vitamin K3 can be used as an adjunct to antimicrobial blue light therapy, increasing the effectiveness of this modality in the treatment of biofilm infections, thereby presenting a potential alternative to antibiotic therapy, to which biofilm infections are so resistant.

Yan M, Wu M

Exercise, especially anaerobic one, can gradually increase muscle mass over time as a result of adaptive responses of muscle cells to ensure metabolic homeostasis in the tissue. Low-level light therapy (LLLT) or photobiomodulation exhibits beneficial effects on promoting muscular functions, regeneration, and recovery from exhausting exercise, although the underlying cellular mechanisms remain poorly understood. We found that hypoxia, a condition following anaerobic exercise, significantly impeded myotube differentiation from myoblasts. However, this adverse effect was blunted greatly by pre-exposure of myoblast cells to a 980 nm laser at 0.1 J/cm2 , resulting in almost nearly normal myotube differentiation. LLL pre-treatment enhanced myotube formation by 80%, with a tubular diameter of 4.28 ± 0.11 μm on average, representative of a 53.4% increase over sham light treatment. The normalized myoblast differentiation concurred with 68% more mitochondrial mass and myogenin expression over controls. Moreover, LLL pre-treatment appeared to enhance glucose uptake, prevent energy metabolic switch from oxidative phosphorylation to glycolysis, and diminish lactate production under hypoxic conditions. The observation provides valuable guidance with respect to the timing of LLLT and its potential effects on muscle strengths in concert with anaerobic exercise.

Yan, M., & Wu, M. X. (2023). Low-Level Light Pre-Conditioning Promotes C2C12 Myoblast Differentiation Under Hypoxic Conditions. Journal of Biophotonics. https://doi.org/10.1002/jbio.202100246

Ong J, Godfrey R, Nazarian A, Tam J, Drake L, Isaacson B, Pasquina P, Williams D

Biofilm contamination is often present at the skin-implant interface of transfemoral osseointegrated implants leading to frequent infection, irritation, and discomfort. New biofilm management regimens are needed as the current standard of washing the site with soap and water is inadequate to manage infection rates. We have investigated the potential of antimicrobial blue light which has reduced risk of resistance development and broad antimicrobial mechanisms. Our lab has developed an aBL device uniquely designed for an ex vivo system based on an established ovine OI implant model with Staphylococcus aureus ATCC 6538 biofilms as initial inocula. Samples were irradiated with aBL or washed for three consecutive days after which they were quantified. Colony forming unit (CFU) counts were compared to a control group (bacterial inocula without treatment). After one day, aBL administered as a single 6 h dose or two 1 h doses spaced 6 h apart both reduced the CFU count by 1.63 log10 ± .02 CFU. Over three days of treatment, a positive aBL trend was observed with a maximum reduction of ~2.7 log10 CFU following 6 h of treatment, indicating a relation between multiple days of irradiation and greater CFU reductions. aBL was more effective at reducing the biofilm burden at the skin-implant interface compared to the wash group, demonstrating the potential of aBL as a biofilm management option.

Ong, J., Godfrey, R., Nazarian, A., Tam, J., Drake, L., Isaacson, B., Pasquina, P., & Williams, D. (2023). Antimicrobial Blue Light as a Biofilm Management Therapy at the Skin-Implant Interface in an Ex Vivo Percutaneous Osseointegrated Implant Model. Journal of Orthopaedic Research. https://doi.org/10.1002/jor.25535

Yuan X, Pav V, Colahan C, Miller M, Nelson H, Pasquina P, Cohen S, Isaacson B

Low back pain (LBP) has accounted for the most medical encounters every year for the past decade among Active-Duty Service Members (ADSMs) of the U.S. Armed Forces. The objectives of this retrospective, descriptive study was to classify LBP by clinical category (Axial, Radicular, and Other) and duration (Acute, Subacute, and Chronic) and examine the LBP-related health care utilization, access to care, and private sector costs for ADSMs over a 2-year follow-up period. The Military Health System Data Repository was queried in fiscal year 2017 for all ADSMs (ages 18-62) with outpatient encounters documented with any of 67 ICD-10 diagnosis codes indicative of LBP. A 1-year clean period before the first (index) outpatient LBP encounter date was used to ensure no recent history of LBP care. Patients were eligible if continuously enrolled and on active duty for 1 year before and 2 years following the index visit. Patients were excluded for non-musculoskeletal causes for LBP, red flags, or acute trauma within 4 weeks of the index visit and/or systemic illness or pregnancy anytime during the clean or follow-up period.

Yuan, X., Pav, V., Colahan, C., Miller, M. E., Hager, N. A., Pasquina, P. F., Cohen, S. P., & Isaacson, B. M. (2022). Active-Duty Service Members Newly Presenting with Low Back Pain in Fiscal Year 2017: Health Care Utilization, Access to Care, and Private Sector Costs Over 2-year Follow-up. Military Medicine. https://doi.org/10.1093/milmed/usac363