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

Bacterial biofilms readily develop on all medical implants, including percutaneous osseointegrated (OI) implants. With the growing rate of antibiotic resistance, exploring alternative options for managing biofilm-related infections is necessary. Antimicrobial blue light (aBL) is a unique therapy that can potentially manage biofilm-related infections at the skin-implant interface of OI implants. Antibiotics are known to have antimicrobial efficacy disparities between the planktonic and biofilm bacterial phenotypes, but it is unknown if this characteristic also pertains to aBL. In response, we developed experiments to explore this aspect of aBL therapy.

aBL had the most significant efficacy disparity between the planktonic and biofilm phenotypes (a 2.5 log10 unit difference). However, further testing against biofilms revealed that aBL had a positive correlation between increasing efficacy and exposure time, while levofloxacin encountered a plateau. While aBL efficacy was affected the most by the biofilm phenotype, its antimicrobial efficacy did not reach a maximum.

We determined that phenotype is an important characteristic to consider when determining aBL parameters for treating OI implant infections. Future research would benefit from expanding these findings against clinical S. aureus isolates and other bacterial strains, as well as the safety of long aBL exposures on human cells.

Ong J, Godfrey R, Nazarian A, Tam J, Isaacson BM, Pasquina PF and Williams DL (2023) Comparison of Staphylococcus aureus tolerance between antimicrobial blue light, levofloxacin, and rifampin. Front. Microbiol. 14:1158558. doi: 10.3389/fmicb.2023.1158558

Smith m, Abboud Chalhoub c, Hogaboom n, St Laurent m, Yuan x, Nordstrom m

Abstract accepted as a poster for 2023 USU Reserach Days

Chronic neck pain is a common health condition for Active Duty military personnel across all occupational specialties. The reduction of cervical lordosis in forward head posture (FHP) can lead to muscular imbalances, degenerative spinal changes, and heightened neck pain. The efficacy of a FHP therapy collar is being explored within the military population with chronic neck pain in an ongoing randomized waitlist-controlled trial at the Walter Reed National Military Medical Center (WRNMMC).

Evaluating the treatment effect of a simple, non-invasive, wearable device for neck pain is highly relevant to the military. This ongoing trial at WRNMMC will shed further light on the potential utility of this novel device in reducing neck pain due to FHP, and thereby improve functional outcomes and operational readiness.

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

Wentz G, Landry P, Yang K, Reilly N, Gonnella M, Wilson V, Goss D

Abstract submitted to American College of Sports Medicine Annual Meeting & World Congresses 2023

This clinical case involved a 38-year-old male soldier presented with lateral knee instability and pain, sustained 1.5 months previously during downhill trail running. Mechanism of injury was reported valgus knee collapse while planting out of a creek. Post-injury follow-up revealed unremarkable imaging for acute pathologies. Initial subjective measures collected included Single Assessment Numeric Evaluation (SANE) of 70% and resting Numeric Pain Rating Scale (NPRS) score of 2 out of 10. Patient demonstrated minimal effusion. Squat test highlighted pain from 30 to 60 degrees of knee flexion and moderate valgus with internal rotation collapse. Pain with end range knee flexion, painful knee extension (NPRS: 5 of 10) with manual muscle test. Tenderness of lateral joint line and lateral femoral condyle was observed. Patient exhibited positive signs during Thessaly test, varus stress test at 0 and 30 degrees, and Nobles and Rennes test.

Eliason A, Weart A, Miller E, Reilly N, Haltiwanger H, Gonnella M, Crowell M, Goss D

Abstract submitted to American College of Sports Medicine Annual Meeting & World Congresses 2023

Despite the inherently dangerous nature of combat, the most prevalent cause of injury observed in military servicemembers (MSMs) stems from running, possibly due to the large cumulative mechanical stresses incurred. Running-related injuries in the military have primarily been addressed by in-person rehabilitation, but limitations exist inequipment and clinician availability. Recently, telehealth has emerged as a method to reach and provide rehabilitative care to a greater number of patients as well as populations without ready access to laboratory-grade assessment tools. However, applications of telehealth for targeting biomechanical parameters associated with running-related injury in the armed services to improve clinical outcomes have not been explored. The purpose is to evaluate the viability of telehealth gait retraining as a modality to identify and modify gait-related kinetic parameters conducive to running-related injury risk in MSMs.

Yang K, Weart A, Miller E, Reilly N, Crowell M, Ford K, Mulier L, Goss D

Abstract submitted to American College of Sports Medicine Annual Meeting & World Congresses 2023

Running is the primary cause of musculoskeletal injury and lost or limited duty days in military service members (MSMs). Telehealth gait retraining is an accessible healthcare intervention showing promise in altering foot strike patterns that influences kinetic and spatiotemporal parameters, reducing mechanical strain and potentially reducing injury risk. However, it is inconclusive whether biomechanical changes resulting from telehealth gait retraining persist after the intervention is completed. The purpose is to determine the long-term efficacy of an 8-week telehealth gait retraining program to target and modify gait-related kinematic parameters.

Reilly N, Miller E, Weart A, Haltiwanger H, McHenry P, Ford K, Crowell M, Goss D

Abstract submitted to American College of Sports Medicine Annual Meeting & World Congresses 2023

Running is the most common mechanism of injury in the military service member (MSM) population. Specifically, cumulative stresses incurred using suboptimal kinematic patterns continuously predispose MSMs to increased risks of running-related injury. The gold-standard laboratory-grade equipment and time requirements necessary for biomechanical analyses of gait are unavailable for the MSM population. Recently, the advent of telehealth has diversified options and access to clinical treatment for a variety of pathologies. However, the effectiveness of telehealth to address risk factors contributing to running-related injury for MSMs is, to date, largely unexplored. The purpose is to evaluate the efficacy of telehealth gait retraining in addressing kinematic risk factors associated with running-related musculoskeletal injury in military personnel.

Goss D, Ignacio G, Helton M, Gonnella M, Reilly N, Haltiwanger, Yang K, Gailey

Abstract submitted to American College of Sports Medicine Annual Meeting & World Congresses 2023

Musculoskeletal injuries (MSI) affect approximately 800,000 service members and 25 million days of limited duty annually. There is a need for quick screening assessments that can classify and predict the risk of lower extremity (LE) MSI prior to activity. An Injury Risk Index (IRI) could facilitate improved decision-making and reduce the negative impact associated with selected MSI. The purpose of this study is to determine the frequency and distribution of Soldiers’ risk of MSI injury after performing sensors-based objective LE tests for static and dynamic stability. As of December 2022, 263 (92% male, 8% female) United States Army Soldiers were recruited, and provided demographic and previous joint-specific injury history information. Soldiers donned a sleeve with two inertial measurement unit sensors over each knee. They performed single limb stance (SLS) tests to obtain Region of Limb Stability (ROLS) values, which measures static LE stability. A four-meter sidestep test (FmSST) was used to obtain the Transitional Angular Displacement of Segments (TADS) values as a metric of dynamic joint stability. The ROLS and TADS symmetry values between LEs is calculated for both tests and the values are used to determine IRI category as low, moderate, or high risk for injury. [RN1] Total assessment time was < 15 minutes per Soldier. Descriptive statistics and frequency distributions were used to characterize the study population.

Crowell M, Pitt W, Mason J, Posner M, Cameron K, and Goss D

Abstract selected for a podium presentation at 2023 American Physical Therapy Association Combined Sections Meeting in San Diego, California

Shoulder instability is common in active young athletes and military personnel, often requiring shoulder stabilization surgery. Acute post-operative pain is usually managed with opioid pain medications, which have adverse effects that reduce military readiness. Battlefield Acupuncture (BFA) has demonstrated promise as a non-pharmaceutical intervention for acute post-operative pain. The purpose of this randomized clinical trial was to assess the effectiveness of BFA on post-surgical pain and opioid medication usage.

Symsack A, Haynes J, Gaunaurd I, Clemens S, Gruenhagen Lucarevic J, Bennet C, Isaacson B, Pasquina P, Gailey R

Abstract selected for a podium presentation at 2023 American Physical Therapy Association Combined Sections Meeting in San Diego, California

Veterans with lower limb loss (LLL) face many challenges (time and cost) to receive appropriate prosthetic training and exercises that could improve their gait quality and functional mobility. The VA and DoD supported the development of the Mobile Device Outcomes-based Rehabilitation Program (MDORP). MDORP is a comprehensive mobile rehabilitation program that includes a wearable sensor system called the Rehabilitative Lower Limb Orthopedic Assistive Device (ReLOAD). The ReLOAD system assesses gait and provides real-time audio feedback during home walks to correct specific gait deviations and subsequently recommend targeted exercises. The purpose of this study was to examine the changes in mobility, gait quality, and strength for lower functioning Veterans with LLL after completing the 8-week MDOR Pprogram

Cohen S, Khunsriraksakul c, Yoo y, Parker E, Samen-Akinsiku c, Patel n, Cohen s, Yuan x, Cheng j, Moon j

Ketamine infusions are frequently employed for refractory complex regional pain syndrome (CRPS), but there are limited data on factors associated with treatment response. Sympathetic blocks are also commonly employed in CRPS for diagnostic and therapeutic purposes and generally precede ketamine infusions.

Factors associated with a positive response to ketamine in univariable analysis were the presence of SMP (61.0% success rate vs 26.7% in those with sympathetically independent pain; P = .009) and post-block temperature increase (5.66 ± 4.20 in ketamine responders vs 3.68 ± 3.85 in non-responders; P = .043). No psychiatric factor was associated with ketamine response. In multivariable analysis, SMP (OR 6.54 [95% CI 1.83, 23.44]) and obesity (OR 8.75 [95% 1.45, 52.73]) were associated with a positive ketamine infusion outcome.

The response to sympathetic blocks may predict response to ketamine infusion in CRPS patients, with alleviation of the affective component of pain and predilection to a positive placebo effect being possible explanations.

Pain Medicine, Volume 24, Issue 3, March 2023, Pages 316–324, https://doi.org/10.1093/pm/pnac153

Miller E, mason J, Pitt w, Crowell M, Wear A, Reilly N, Haltiwanger H, Gonnella M, Goss D

Abstract selected for a podium presentation at 2023 American Physical Therapy Association Combined Sections Meeting 2023 in San Diego, California

Previous research has identified numerous biomechanical variables that may relate to musculoskeletal injury risk. Gait retraining interventions have successfully altered running biomechanical risk factors for overuse knee injury in non-military populations. However, constraints on patient time and frequency of in-clinic visits limits implementation of gait retraining interventions in the Military Health System (MHS). The purpose of this randomized clinical trial was to determine the effect of a telehealth gait retraining intervention on the running kinematics in patients with an overuse knee injury.

Rhon D, Yuan X, Barlow B, Konitzer L, Cook C

Within a large government health system, to assess the practice of using non-specific diagnoses for knee disorders and determine how often they appear as the only diagnosis without more specificity. The secondary purpose was to identify the incidence of obscure knee disorders diagnosed: pes anserine bursitis, prepatellar bursitis, pigmented villonodular synovitis, and plica syndrome.

Rhon, Daniel & Yuan, Xiaoning & Barlow, Brian & Konitzer, Lisa & Cook, Chad. (2022). Use of Non-Specific Knee Diagnoses and Incidence of Obscure Knee Injuries in a Large Government Health System. Clinical Epidemiology. Volume 14. 1123-1133. https://doi.org/10.2147/CLEP.S375040

RHON D, TEYHEN D, COLLINS G, BULLOCK G

Abstract submitted to The World Congress of Sports Physical Therapy 2022

Using the same data, compare performance between an injury prediction model categorizing predictors and one that did not, and compare selection of predictors based on univariate significance versus assessing non-linear relationships. Validation and replication of a previously developed injury prediction model in a cohort of 1466 healthy military service members followed for one year after physical performance, medical history, and sociodemographic variables were collected. The original model dichotomized 8 predictors. The second model (M2) kept predictors continuous but assumed linearity, the third model (M3) conducted non-linear transformations. The fourth model (M4) chose predictors the proper way (clinical reasoning and supporting evidence) which led to an addition of 7 additional predictors (15 predictors total), but still kept predictors dichotomized. Model performance was assessed with R2, calibration in the large, calibration slope, and discrimination. Decision curve analyses were performed with risk thresholds from 0.25 to 0.50.

Persinger J and Hager N

Abstract submitted to American Institute of Ultrasound in Medicine 2022

The Physical Medicine and Rehabilitation Clinic (PM&R) at Walter Reed National Military Medical Center (WRNMMC) augmented their high frequency ultra-sound systems with an ultra-high frequency ultrasound (UHFUS) system for use in the diagnosing and treatment of musculoskeletal (MSK) and nerve injury warfighters. The Visualsonics VevoMD is an UHFUS system with operating frequencies in the 24–70 MHz range as compared to the typical POC and tertiary care ultrasound systems operating in the15–22 MHz range. Access to this system afforded a unique opportunity to explore the usefulness of this cutting-edge technology in the unique settings of limb loss and multi-trauma in the military.

Tenforde A, Vogel K, Tam J, Grävare Silbernagel K

Achilles tendinopathy (AT) is a common overuse injury in runners. While the mainstay of treatment for AT is tendon loading exercises (physical therapy and exercise programme (EXER)), some patients have refractory symptoms. Extracorporeal shockwave therapy (ESWT) and photobiomodulation therapy (PBMT) have each been evaluated to facilitate tendon healing; the influence of combining treatments is unknown and limited studies have been completed in runners. This randomized control study, with an elective cross-over at 3 months, will evaluate the efficacy of three forms of treatment of non-insertional AT: (1) EXER (loading programme specific to Achilles tendon combined with physical therapy); (2) EXER and ESWT; (3) EXER, ESWT and PBMT. Sixty runners will be assigned using block randomization into one of three treatment groups (n=20). After 3 months, each participant may elect a different treatment than previously assigned and will be followed for an additional 3 months. The EXER Achilles loading programme will be standardized using the Silbernagel at-home programme. The primary outcome of interest is treatment group responses using the Victorian Institute of Sports Assessment—Achilles (VISA-A) Score. Secondary outcomes include the Patient-Reported Outcomes Measurement Information System—29 questions, the University of Wisconsin Running Injury and Recovery Index, heel raise to fatigue test, hopping test and ultrasound measurements. We will also capture patient preference and satisfaction with treatment. We hypothesize that the cohorts assigned EXER+ESWT+PBMT and EXER+ESWT will see greater improvements in VISA-A than the EXER cohort, and the largest gains are anticipated in combining ESWT+PBMT. The elective cross-over phase will be an exploratory study and will inform us whether patient preference for treatment will impact the treatment response.

Tenforde, A. S., Vogel, K. E. L., Tam, J., & Grävare Silbernagel, K. (2022). Research protocol to evaluate the effectiveness of shockwave therapy, photobiomodulation and physical therapy in the management of non-insertional Achilles tendinopathy in runners: a randomized control trial with elective cross-over design. BMJ Open Sport & Exercise Medicine. https://doi.org/http://dx.doi.org/10.1136/bmjsem-2022-001397