Galvin J, Patteron B, Bozoghlian m, nepola j, colburn z

A biorepository, also referred to as a “biobank,” is a collection of biologic samples that are stored for laboratory research. With the emergence of precision medicine, the importance of leveraging individual patient biomolecular signatures to improve diagnosis, prognosis, and treatment is becoming increasingly recognized. Successful development and sustainment of a biorepository provides the potential for transformative preclinical research. Establishing a biobank requires a team approach with involvement of the institutions' research laboratory team and regulatory body. Execution of research activities requires a coordinated team approach for case identification, consent process, data and specimen collection, specimen processing, and storage and archiving. The advancing fields of precision medicine and orthobiologics provide incredible opportunities for institutions to generate novel lines of inquiry in musculoskeletal diseases through a multiomics approach (genomic, transcriptomic, proteomic, microbiomic). In addition, a biobank is an important component of post-market surveillance for the rapidly emerging field of orthobiologics.

Galvin, Joseph W. DO; Patterson, Brendan M. MD, MPH; Bozoghlian, Maria MD; Nepola, James V. MD; Colburn, Zachary T. PhD, MBA, MS. Musculoskeletal Biorepository: Establishment, Sustainment, and Tips for Success. Journal of the American Academy of Orthopaedic Surgeons ():10.5435/JAAOS-D-24-00153, April 17, 2024. | DOI: 10.5435/JAAOS-D-24-00153

Galvin J, Milam R, Patterson B, nepola J, buckwalter j, wolf b, say f, free k, yohannes e

The incremental biological changes in the synovial microenvironment of the shoulder in acute and chronic instability that may contribute to joint degeneration are poorly understood. Proteomic analysis of synovial fluid in patients with shoulder instability may improve our understanding of proteins that are shed into shoulder synovial fluid after an injury.

Proteomic analysis enriched our understanding of proteins that were secreted into shoulder synovial fluid of patients with shoulder instability. The identification of POSTN, a proinflammatory catabolic protein involved with tissue remodeling and repair, as a significant target in anterior shoulder instability is a novel finding. Therefore, further study is warranted to determine the role that POSTN may play in the progression of bone loss and posttraumatic osteoarthritis.

Galvin JW, Milam RJ, Patterson BM, Nepola JV, Buckwalter JA 4th, Wolf BR, Say FM, Free KE, Yohannes E. Periostin Is a Biomarker for Anterior Shoulder Instability: Proteomic Analysis of Synovial Fluid. Am J Sports Med. 2024 May 4:3635465241246258. doi: 10.1177/03635465241246258. Epub ahead of print. PMID: 38702960.

dowe j, bradley m, leclere l, dickens j

Understanding the anatomical structure of a patient’s shoulder joint is essential in surgical decision-making, especially regarding glenohumeral bone loss. The use of various imaging techniques, such as magnetic resonance imaging (MRI) and computed tomography (CT), bring certain advantages and disadvantages in assessing joint structure.

The process of obtaining a 3D view of the shoulder joint from an MRI, although less common, can be completed effectively to assess bone loss while also solving some issues surrounding CT scans. By loading MRI datasets into an image-reformation program, such as 3D Slicer, the anatomical structures can be segmented to create realistic 3D models of the shoulder joint. Surgical direction can be determined after bone loss measurements and structural assessment of these models, without the need for CT scans. This technique can also be applied to other skeletal joints, in addition to the shoulder.

Dowe, J. N., Bradley, M. W., LeClere, L. E., & Dickens, J. F. (2024). Creating a Three-Dimensional Reconstruction of the Glenohumeral Joint From Magnetic Resonance Imaging to Assist in Surgical Decision-Making. Journal of Emerging Advanced Technology in Surgery, 1(1), 102972. https://doi.org/10.1016/j.eats.2024.102972

rhon d, Drysdale l, radcliffe c, newman p

rhon d, Davis A, Ali J, Brandt C, Burns A, Lucio W, Vining R, Young-mccaughan S

Pragmatic clinical trials (PCTs) often study interventions delivered within the context of standard clinical encounters with the overall goal of producing generalisable knowledge to inform implementation strategies and health policy. In reality, however, PCTs have a gradient of pragmatic and explanatory features, as described by the PRagmatic Explanatory Continuum Indicator Summary, 2nd edition (PRECIS-2) framework. To facilitate the process of iterative learning, PCTs and comparative effectiveness trials frequently test interventions shown to be effective in explanatory trials, the latter having more stringent entry criteria. PCTs are particularly valuable for assessing use of non-pharmacological interventions, such as those designed to manage pain. Conducted in settings involving a broad range of patients and delivered by a range of qualified clinicians that may or may not have a research background, PCTs can illuminate implementation barriers and practice variations affecting the delivery of clinical interventions that may or may not be widely supported by institutional culture.

The purpose of this manuscript is to clearly define and differentiate usual care and validated care, such that these terms can be considered generically as part of regulatory activities that affect PCTs.

Rhon DI, Davis AF, Ali J, et alAmbiguity in care delivery terminology: implications that affect pragmatic clinical trials using non-pharmacological interventionsBMJ Evidence-Based Medicine Published Online First: 21 November 2023. doi: 10.1136/bmjebm-2023-112547

Galvin J, Rooney P, Tokish J, Grassbaugh J, Masini B, Free K, Bastian M, Gillette L, Colburn Z

Abstract accepted for poster presentation at the 2024 Arthroscopy Association of North America (AANA) Annual Meeting

Currently the measurement of serum or synovial biomarkers does not have a role in diagnosis or monitoring of injury severity in young patients with recurrent anterior shoulder instability. The purpose of this study was to compare gene expression differences in the peripheral blood and tissue of young patients with recurrent anterior shoulder instability with and without significant glenoid bone loss (GBL). Additionally, we sought to determine a peripheral blood transcriptomic biomarker for the reliable delineation of the severity of GBL in anterior shoulder instability patients.

There are significant gene expression differences in the peripheral blood of anterior shoulder instability patients with and without significant (≥10%) GBL. The differential expression of 5 genes allowed development of an accurate predictive model and transcriptomic classifier to predict the severity of GBL. This novel peripheral blood transcriptomic biomarker may assist in tracking glenoid bone loss and injury severity and progression in young patients with recurrent anterior shoulder instability.

Velasco t, Reilly n, Roberts k, Hulsopple c, Hoellen d, Wise S, Dickison c, Goss d, Leggit j

Abstract accepted for a poster presentation at the 2024 Alexander T. Augusta Military Medical Center (ATAMMC) Research Day

Chronic exertional compartment syndrome (CECS) is characterized by intense localized pain, weakness, or paresthesia in the lower limb muscles, exacerbated by running.1,2 This condition significantly impairs active-duty service members (ADSMs) who regularly engage in running activities. While surgical interventions have shown mixed results, the exploration of non-surgical and pharmaceutical options, particularly botulinum toxin A (BoNT-A) and gait retraining, has gained attention.2-5 The purpose of this case series was to examine the biomechanical gait patterns observed in ADSMs with CECS pre and post non-surgical treatment.

In this case serires, the administration of BoNT-A was shown to be associated with more positive outcomes on pain reduction during running without leading to the adoption of gait patterns associated with injury risk. More extensive research is warranted to examine the effectiveness of BoNT-A for CECS from longitudinal perspectives.

Galvin J, egan a, Rooney P, Grassbaugh J, Masini B, Free K, Bastian M, Gillette L, Colburn Z

Abstract accepted for a poster presentation at the 2024 Madigan Research Day

Little is known about the pathobiology of unidirectional anterior and posterior shoulder instability. The purpose of this study was to compare gene expression differences in the peripheral blood and capsular tissue of young patients with recurrent anterior shoulder instability and those patients with unidirectional posterior shoulder instability.

There are significant gene expression differences in the shoulder capsule of anterior and posterior shoulder instability patients. This transcriptomic data may provide an improved understanding of the pathobiology of various forms of shoulder instability which could lead to future precision medicine approaches.

Galvin J, Rooney P, Tokish J, Grassbaugh J, Masini B, Free K, Bastian M, Gillette L, Colburn Z

Abstract accepted for poster presentation at the 2024 Madigan Research Day

Currently the measurement of serum or synovial biomarkers does not have a role in diagnosis or monitoring of injury severity in young patients with recurrent anterior shoulder instability. The purpose of this study was to compare gene expression differences in the peripheral blood and tissue of young patients with recurrent anterior shoulder instability with and without significant glenoid bone loss (GBL). Additionally, we sought to determine a peripheral blood transcriptomic biomarker for the reliable delineation of the severity of GBL in anterior shoulder instability patients.

There are significant gene expression differences in the peripheral blood of anterior shoulder instability patients with and without significant (≥10%) GBL. The differential expression of 5 genes allowed development of an accurate predictive model and transcriptomic classifier to predict the severity of GBL. This novel peripheral blood transcriptomic biomarker may assist in tracking glenoid bone loss and injury severity and progression in young patients with recurrent anterior shoulder instability.

Persinger J, Hager N

The Incidence of stress fractures in military members has been reported to range from .8%-6.9% for men and from 3.4% - 21% for women.   The early identification is critical to optimizing treatment for bone stress injuries (BSI). The current gold standard for diagnosing BSI is either triple-phase, Bone scintigraphy technetium-99m, MRI or CT. Diagnostic, high frequency ultrasound (US) has been demonstrated to identify early periosteal changes in BSI.

This case report concluded that high frequency ultrasound is a relibale and accurate modality for early diagnosis of BSI and assiting with return to duty decision making. This diagnostic imaging tool for BSI is valuable, inexpensive, and easily accesible. Future studies are warranted to determine whether US could be a competitive screening tool vs MRI for initial BSI diagnosis

Persinger j, gabler g, hager n

Successful delivery of a Diagnostic Musculoskeletal US program requires a combination of hands-on experience with the ultrasound system, a thorough review of applicable, regional pathophysiology, and an overview of the technology aspects of the US acquisition system. Most often, these programs are delivered over several months in an in-person, academic setting that allows for student-educator, student-equipment, and student-patient interactions. During the initial COVID-19 outbreak and in response to campus policy and public mandates for distant learning, the Department of Physical Medicine and Rehabilitation at Uniformed Services University of the Health Sciences (USUHS) transformed a musculoskeletal (MSK) ultrasound clerkship into a virtual platform - training students deployed locally, nationally, and internationally. This modification of the educational approach allowed for delivering a high quality MSK Ultrasound Curriculum in a safe and often remote environment. Further, many of the successes gleaned from this experience during the pandemic enhanced future MSK educational programs for both medical students and physicians.

The implementation of the virtual MSK US clerkship at USUHS represents a paradigm shift for the department in providing training in hands-on skills for diagnostic sonography with direct application to clinical care. The ability to link students and instructors without geographical limitations provided a positive long-term impact on future similarly patterned courses. It also enabled this team to take lessons learned from the program and apply them to remote clinical education opportunities in the future.

Persinger J, Hager N, Grogan S, Mincey C

The Geneva Foundation (Tacoma, WA) in conjunction with Uniformed Services University of the Health Sciences (USUHS), and the Podiatry Clinic at Madigan Army Medical Center (MAMC) is conducting a research study to establish normative values for thickness and cross-sectional area (CSA), microvascular flow states, power Doppler flow states, and Young’s modulii in the posterior lower leg muscles (gastroc/soleus) and Achilles tendon. This study supports a concurrent study attempting to validate shear-wave elastography (SWE) and microvascular flow (MVF) as a novel, sensitive, and non-invasive means of determining the health and recovery state of the above structures.

Achilles tendinopathy, plantar fasciitis, and chronic exertional compartment syndrome (CECS) are commonly seen in the active-duty service member and military recruit population. These conditions are common contributors to significant warfighter disability, impacting operational readiness. Non-invasive technology such as microvascular flow and shear wave elastography may prove to be timely and cost effective.

Persinger J, Hager N, Gabler G, Karikari N, Rossi R, Schroeder J

Non-insertional Achilles Tendinopathy (AT) is a common overuse injury in adults whether athletes or inactive individuals. In the US military, lower extremity issues due to overuse, such as AT, are the most common category of injuries, with the highest occurrence in the Army. The current management of AT is largely conservative, although approximately 25%-29% of patients require surgical intervention. Photobiomodulation Therapy (PBMT) has been shown to decrease inflammation while increasing cell proliferation and metabolism which has been reported to aid in healing and more specifically with tendon repair. Additionally, Extracorporeal shockwave therapy (ESWT or SWT) is a process in which energy is delivered to muscles and tendons for pain relief and improved function. The best available evidence suggests that a combination of ESWT with eccentric exercises and stretching may be even more effective than ESWT. Diagnostic MSK Ultrasound with high frequency linear transducer has become the standard of care in the evaluation of AT, being used as a screening modality, to monitor disease process, and to direct treatment interventions. Additionally, more advanced & complementary ultrasound capabilities, such as elastography (SWE), and microvascular flow (MVF) have been developed to improve diagnostic acumen. The Geneva Foundation (Tacoma, WA) in conjunction with Uniformed Services University of the Health Sciences (USUHS), and the Family Medicine Department at Madigan Army Medical Center (MAMC) is conducting a Randomized Control Trial to evaluate and contrast the effectiveness of standard PT, SWT, vs PBMT in treating non-insertional Achilles tendinopathy. Diagnostic MSK Ultrasound is serving a pivotal role in screening and monitoring the treatment effects and this abstract/presentation will focus on describing this role through discussion of the equipment capabilities and findings as well as the relative changes in echo-architecture with each of the comparative arms.

Diagnostic MSK ultrasound serves a critical role in the screening, diagnosis and monitoring of these Achilles tendinopathy patients. No other imaging modality would permit the level of discrimination of pathology required in this Achilles tendinopathy study. Diagnostic MSK ultrasound with the unique, complimentary upgrades (described above) served to greatly improve overall assessment of the ongoing pathophysiologic changes within the tendon fibers throughout the course of treatment for Achilles tendinopathy. There are various pitfalls and technique optimizations that should be considered when evaluating the Achilles as described above. Accounting for these can greatly enhance the diagnostic acumen of the US Study.

Jariwala S, Fellin C, Steiner R, Buchen J, ANders J

Peripheral nerve injuries (PNI) pose a significant clinical issue for patients, especially in the most severe cases where complete transection (neurotmesis) results in total loss of sensory/motor function. Nerve guidance conduits (NGCs) are a common treatment option that protects and guides regenerating axons during recovery. However, treatment outcomes remain limited and often fail to achieve full reinnervation, especially in critically sized defects (> 3 cm) where a lack of vascularization leads to neural necrosis. A multi-treatment approach is therefore necessary to improve the efficacy of NGCs. Stimulating angiogenesis within NGCs can help alleviate oxygen deficiency through rapid inosculation with the host vasculature, while photobiomodulation therapy (PBMT) has demonstrated beneficial therapeutic effects on regenerating nerve cells and neovascularization.

In this review, we discuss the current trends of NGCs, vascularization, and PBMT as treatments for peripheral nerve neurotmesis and highlight the need for a combinatorial approach to improve functional and clinical outcomes

Photobiomodulation Photomedicine Laser Surgery. Published 2023 December 18. doi: 10.1089/photob.2023.0103.