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Article ; Online: Volumetric Muscle Loss: A Bibliometric Analysis of a Decade of Progress.

Kulwatno, Jonathan / Goldman, Stephen M / Dearth, Christopher L

2023 Volume 29, Issue 3, Page(s) 299–309

Abstract: The consequences of military conflict, accidents, and diseases have led to the definition-and subsequent study-of the pathological condition now known as volumetric muscle loss (VML). VML is a significant injury to skeletal muscle tissue on a scale that ... ...

Abstract	The consequences of military conflict, accidents, and diseases have led to the definition-and subsequent study-of the pathological condition now known as volumetric muscle loss (VML). VML is a significant injury to skeletal muscle tissue on a scale that is endogenously irrecoverable and leads to chronic functional deficits and long-term disability. Currently, there lacks a definitive approach to meaningfully restore the tissue and function lost by those afflicted, ushering a need for scientific activities and associated funding to both facilitate a deeper understanding of the pathobiology of VML as well as to develop and assess clinically relevant therapeutics and treatment strategies. Thereby, evaluation of the VML field is crucial to gauging the return on resource expenditures and to understand the evolution of the field to guide future directions. This article presents a bibliometric analysis of publicly available data to explore the growth of the VML field since its genesis and to highlight its prosperity through its expanding literature, its development and evaluation of promising treatment strategies, rising financial investments, and innovation. Altogether, the bibliometric analysis reveals the field of VML as an emergent research focus that is productive and translational. Impact statement Analyses of a research topic are fundamental toward evaluating the returns on investment and appreciating the evolution of the research toward novel directions. This study aims to highlight the growing field of volumetric muscle loss (VML), defined as a significant injury to skeletal muscle tissue that leads to functional impairment and is irrecoverable through inherent regenerative mechanisms. The analysis of bibliometric and publicly available data provides evidence that the field of VML has an expanding research interest and investment, with biomaterials at the forefront of study.
MeSH term(s)	Humans ; Muscular Diseases/therapy ; Regeneration/physiology ; Muscle, Skeletal/physiology ; Bibliometrics
Language	English
Publishing date	2023-03-17
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2420584-9
ISSN	1937-3376 ; 1937-3368
ISSN (online)	1937-3376
ISSN	1937-3368
DOI	10.1089/ten.TEB.2022.0150
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Repurposing existing products to accelerate injury recovery (REPAIR) of military relevant musculoskeletal conditions.

Clark, Andrew R / Mauntel, Timothy C / Goldman, Stephen M / Dearth, Christopher L

Frontiers in bioengineering and biotechnology

2023 Volume 10, Page(s) 1105599

Abstract: Musculoskeletal injuries (MSKIs) are a great hindrance to the readiness of the United States Armed Forces through lost duty time and reduced operational capabilities. While most musculoskeletal injuries result in return-to-duty/activity with no ( ... ...

Abstract	Musculoskeletal injuries (MSKIs) are a great hindrance to the readiness of the United States Armed Forces through lost duty time and reduced operational capabilities. While most musculoskeletal injuries result in return-to-duty/activity with no (functional) limitations, the healing process is often long. Long healing times coupled with the high frequency of musculoskeletal injuries make them a primary cause of lost/limited duty days. Thus, there exists an urgent, clinically unmet need for interventions to expedite tissue healing kinetics following musculoskeletal injuries to lessen their impact on military readiness and society as a whole. There exist several treatments with regulatory approval for other indications that have pro-regenerative/healing properties, but few have an approved indication for treating musculoskeletal injuries. With the immediate need for treatment options for musculoskeletal injuries, we propose a paradigm of Repurposing Existing Products to Accelerate Injury Recovery (REPAIR). Developing treatments
Language	English
Publishing date	2023-01-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2022.1105599
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Article: Demographics and Comorbidities of United States Service Members with Combat-Related Lower Extremity Limb Salvage.

Goldman, Stephen M / Eskridge, Susan L / Franco, Sarah R / Dearth, Christopher L

Journal of clinical medicine

2023 Volume 12, Issue 21

Abstract: Introduction: This retrospective study describes the demographics and injury characteristics of a recently identified cohort of US Service members with combat-related lower extremity limb salvage (LS).: Methods: US Service members with combat trauma ... ...

Abstract	Introduction: This retrospective study describes the demographics and injury characteristics of a recently identified cohort of US Service members with combat-related lower extremity limb salvage (LS). Methods: US Service members with combat trauma were identified from the Expeditionary Medical Encounter Database and Military Health System Data Repository and stratified into primary amputation (PA), LS, and non-threatened limb trauma (NTLT) cohorts based on ICD-9 codes. Disparities in demographic factors and injury characteristics were investigated across cohorts and within the LS cohort based on limb retention outcome. Results: Cohort demographics varied by age but not by sex, branch, or rank. The mechanism of injury and injury characteristics were found to be different between the cohorts, with the LS cohort exhibiting more blast injuries and greater injury burden than their peers with NTLT. A sub-analysis of the LS population revealed more blast injuries and fewer gunshot wounds in those that underwent secondary amputation. Neither demographic factors nor total injury burden varied with limb retention outcome, despite slight disparities in AIS distribution within the LS cohort. Conclusions: In accordance with historic dogma, the LS population presents high injury severity. Demographics and injury characteristics are largely invariant with respect to limb retention outcomes, despite secondary amputation being moderately more prevalent in LS patients with blast-induced injuries. Further study of this population is necessary to better understand the factors that impact the outcomes of LS in the Military Health System.
Language	English
Publishing date	2023-10-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12216879
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Article ; Online: Retrospective characterization of a rat model of volumetric muscle loss.

Dolan, Connor P / Dearth, Christopher L / Corona, Benjamin T / Goldman, Stephen M

BMC musculoskeletal disorders

2022 Volume 23, Issue 1, Page(s) 814

Abstract: Volumetric muscle loss (VML) is a pervasive injury within contemporary combat and a primary driver of disability among injured Service members. As such, VML has been a topic of investigation over the past decade as the field has sought to understand the ... ...

Abstract	Volumetric muscle loss (VML) is a pervasive injury within contemporary combat and a primary driver of disability among injured Service members. As such, VML has been a topic of investigation over the past decade as the field has sought to understand the pathology of these injuries and to develop treatment strategies which restore the form and function of the involved musculature. To date, much of this work has been performed in disparate animal models that vary significantly in terms of the species utilized, the muscle (or muscle group) affected, and the volume of muscle lost. Moreover, variation exists in the reporting of anatomical and functional outcomes within these models. When taken together, the ability to successfully assess comparative efficacy of promising therapies is currently limited. As such, greater scrutiny on the characterization of these VML models is needed to better assess the quality of evidence supporting further translation of putative therapies. Thus, the objective of this study was to retrospectively characterize anatomical and functional outcomes associated with one such VML model - the 6 mm biopsy punch model of the rat tibialis anterior muscle. Through these efforts, it was shown that this model is highly reproducible and consistent across a large number of experiments. As such, the data presented herein represent a reasonable benchmark for the expected performance of this model with utility for drawing inferences across studies and identifying therapies which have shown promise within the preclinical domain, and thus are ready for further translation towards the clinic.
MeSH term(s)	Animals ; Disease Models, Animal ; Muscle, Skeletal ; Muscular Diseases/pathology ; Rats ; Regeneration/physiology ; Retrospective Studies
Language	English
Publishing date	2022-08-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2041355-5
ISSN	1471-2474 ; 1471-2474
ISSN (online)	1471-2474
ISSN	1471-2474
DOI	10.1186/s12891-022-05760-5
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Article ; Online: Efficacy of non-surgical interventions for promoting improved functional outcomes following acute compartment syndrome: A systematic review.

Janakiram, Naveena B / Motherwell, Jessica M / Goldman, Stephen M / Dearth, Christopher L

PloS one

2022 Volume 17, Issue 9, Page(s) e0274132

Abstract: Background: Acute compartment syndrome (ACS) is a devastating complication which develops following a traumatic extremity injury that results in increased pressure within osteofascial compartments, thereby leading to ischemia, muscle and nerve necrosis, ...

Abstract	Background: Acute compartment syndrome (ACS) is a devastating complication which develops following a traumatic extremity injury that results in increased pressure within osteofascial compartments, thereby leading to ischemia, muscle and nerve necrosis, and creates a life-threatening condition if left untreated. Fasciotomy is the only available standard surgical intervention for ACS. Following fasciotomy the affected extremity is plagued by prolonged impairments in function. As such, an unmet clinical need exists for adjunct, non-surgical therapies which can facilitate accelerated functional recovery following ACS. Thus, the purpose of this systematic review was to examine the state of the literature for non-surgical interventions that aim to improve muscle contractile functional recovery of the affected limb following ACS. Methods: English language manuscripts which evaluated non-surgical interventions for ACS, namely those which evaluated the function of the affected extremity, were identified as per PRISMA protocols via searches within three databases from inception to February 2022. Qualitative narrative data synthesis was performed including: study characteristics, type of interventions, quality, and outcomes. Risk of bias (RoB) was assessed using the Systematic Review Centre for Laboratory Animal Experimentation's (SYRCLE) RoB tool and reported level of evidence for each article. Results: Upon review of all initially identified reports, 29 studies were found to be eligible and included. 23 distinct non-surgical interventions were found to facilitate improved muscle contractile function following ACS. Out of 29 studies, 15 studies which evaluated chemical and biological interventions, showed large effect sizes for muscle function improvement. Conclusions: This systematic review demonstrated that the majority of identified non-surgical interventions facilitated an improvement in muscle contractile function following pathological conditions of ACS.
MeSH term(s)	Compartment Syndromes/surgery ; Extremities ; Fasciotomy/adverse effects ; Fasciotomy/methods ; Humans ; Recovery of Function ; Soft Tissue Injuries
Language	English
Publishing date	2022-09-09
Publishing country	United States
Document type	Journal Article ; Systematic Review
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0274132
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Mechanical loading of bone-anchored implants during functional performance tests in service members with transfemoral limb loss.

Gladish, Jonathan R / Dearth, Christopher L / Beachler, Mark D / Potter, Benjamin K / Forsberg, Jonathan A / Hendershot, Brad D

Frontiers in rehabilitation sciences

2024 Volume 5, Page(s) 1336115

Abstract: Introduction: For individuals with limb loss, bone-anchored implants create a direct structural and functional connection to a terminal prosthesis. Here, we characterized the mechanical loads distal to the abutment during several functional performance ... ...

Abstract	Introduction: For individuals with limb loss, bone-anchored implants create a direct structural and functional connection to a terminal prosthesis. Here, we characterized the mechanical loads distal to the abutment during several functional performance tests in Service members with transfemoral (TF) limb loss, to expand on prior work evaluating more steady-state ambulation on level ground or slopes/stairs. Methods: Two males with unilateral TF limb loss and two males with bilateral TF limb loss participated after two-stage osseointegration (24 and 12 months, respectively). Tri-directional forces and moments were wirelessly recorded through a sensor, fit distal to the abutment, during six functional tests: Timed Up and Go (TUG), Four Square Step Test (FSST), Six Minute Walk Test (6MWT), Edgren Side-Step Test (SST), T-Test (TTEST), and Illinois Agility Test (IAT). Additionally, participants performed a straight-line gait evaluation on a 15 m level walkway at a self-selected speed (0.93-1.24 m/s). Peak values for each component of force and moment were extracted from all six functional tests; percent differences compared each peak with respect to the corresponding mean peak in straight-line walking. Results: Peak mechanical loads were largest during non-steady state components of the functional tests (e.g., side-stepping during SST or TTEST, standing up from the ground during IAT). Relative to walking, peak forces during functional tests were larger by up to 143% (anterior-posterior), 181% (medial-lateral), and 110% (axial); peak moments were larger by up to 108% (flexion-extension), 50% (ab/adduction), and 211% (internal/external rotation). Conclusions: A more comprehensive understanding of the mechanical loads applied to bone-anchored implants during a variety of activities is critical to maximize implant survivability and long-term outcomes, particularly for Service members who are generally young at time of injury and return to active lifestyles.
Language	English
Publishing date	2024-03-15
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-6861
ISSN (online)	2673-6861
DOI	10.3389/fresc.2024.1336115
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Article ; Online ; Conference proceedings: Eighth symposium on biologic scaffolds for regenerative medicine.

Dearth, Christopher L

Regenerative medicine

2014 Volume 9, Issue 5, Page(s) 569–572

Abstract: The Eighth Symposium on Biologic Scaffolds for Regenerative Medicine was held from 24 to 26 April 2014 at the Silverado Resort in Napa, CA, USA. The symposium was well attended by a diverse audience of academic scientists, industry members and physicians ...

Abstract	The Eighth Symposium on Biologic Scaffolds for Regenerative Medicine was held from 24 to 26 April 2014 at the Silverado Resort in Napa, CA, USA. The symposium was well attended by a diverse audience of academic scientists, industry members and physicians from around the world. The conference showcased the strong foundation of both basic and translational research utilizing biologic scaffolds in regenerative medicine applications across nearly all tissue systems and facilitated vibrant discussions among participants. This article provides an overview of the conference by providing a brief synopsis of selected presentations, each focused on a unique research and/or clinical investigation currently underway.
MeSH term(s)	Regenerative Medicine/trends ; Tissue Culture Techniques ; Tissue Engineering/trends ; Tissue Scaffolds/trends
Language	English
Publishing date	2014
Publishing country	England
Document type	Congresses ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2274500-2
ISSN	1746-076X ; 1746-0751
ISSN (online)	1746-076X
ISSN	1746-0751
DOI	10.2217/rme.14.41
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Deleterious Musculoskeletal Conditions Secondary to Lower Limb Loss: Considerations for Prosthesis-Related Factors.

Knight, Ashley D / Dearth, Christopher L / Hendershot, Brad D

Advances in wound care

2020 Volume 10, Issue 12, Page(s) 671–684

Abstract: Significance: ...

Abstract	Significance:
MeSH term(s)	Amputation, Surgical/adverse effects ; Amputation, Surgical/rehabilitation ; Amputees/rehabilitation ; Humans ; Lower Extremity/injuries ; Musculoskeletal Diseases/etiology ; Musculoskeletal Diseases/rehabilitation ; Prostheses and Implants/statistics & numerical data ; Quality of Life
Language	English
Publishing date	2020-05-22
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2650541-1
ISSN	2162-1934 ; 2162-1918
ISSN (online)	2162-1934
ISSN	2162-1918
DOI	10.1089/wound.2019.1079
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Article ; Online: The Role of the Inflammatory Response in Mediating Functional Recovery Following Composite Tissue Injuries.

Janakiram, Naveena B / Valerio, Michael S / Goldman, Stephen M / Dearth, Christopher L

International journal of molecular sciences

2021 Volume 22, Issue 24

Abstract: Composite tissue injuries (CTI) are common among US Military Service members during combat operations, and carry a high potential of morbidity. Furthermore, CTI are often complicated due to an altered wound healing response, resulting in part from a ... ...

Abstract	Composite tissue injuries (CTI) are common among US Military Service members during combat operations, and carry a high potential of morbidity. Furthermore, CTI are often complicated due to an altered wound healing response, resulting in part from a dysregulation of the innate and adaptive immune responses. Unlike normal wound healing, in CTI, disruptions occur in innate immune responses, altering neutrophil functions, macrophage activation and polarization, further impacting the functions of T regulatory cells. Additionally, the biological underpinnings of these unfavorable wound healing conditions are multifactorial, including various processes, such as: ischemia, hypoxia, low nutrient levels, and altered cell metabolic pathways, among others, all of which are thought to trigger anergy in immune cells and destabilize adaptive immune responses. As a result, impaired wound healing is common in CTI. Herein, we review the altered innate and adaptive immune cells and their metabolic status and responses following CTI, and discuss the role a multi-pronged immunomodulatory approach may play in facilitating improved outcomes for afflicted patients.
MeSH term(s)	Adaptive Immunity ; Animals ; Humans ; Immunity, Innate ; Immunomodulation ; Inflammation ; Macrophages ; Neutrophils ; Wound Healing/immunology
Language	English
Publishing date	2021-12-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222413552
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Article ; Online: Evaluation of licofelone as an adjunct anti-inflammatory therapy to biologic scaffolds in the treatment of volumetric muscle loss.

Goldman, Stephen M / Janakiram, Naveena Basa / Valerio, Michael S / Dearth, Christopher L

Cell and tissue research

2021 Volume 385, Issue 1, Page(s) 149–159

Abstract: Biologic scaffolds (BS) are the most widely studied therapeutics for the treatment of volumetric muscle loss (VML) owing to their purported effects on cell proliferation, chemotaxis, migration, and differentiation. Despite these claims, variability in ... ...

Abstract	Biologic scaffolds (BS) are the most widely studied therapeutics for the treatment of volumetric muscle loss (VML) owing to their purported effects on cell proliferation, chemotaxis, migration, and differentiation. Despite these claims, variability in reports on the nature of the immune response to their implantation suggests that BS-associated inflammation may be limiting their regenerative efficacy. To address this shortcoming, this study sought to evaluate licofelone (ML3000), a dual 5-LOX/COX inhibitor, as an anti-inflammatory adjunct therapy to a BS in the treatment of VML. Utilizing a well-established rat VML model, a micronized BS was used to treat the VML injury, with or without administration of licofelone. Functional, molecular, and histological outcomes were assessed at both 7- and 28-day post-injury time points. While the BS + licofelone group exhibited decreased transcription of pro-inflammatory markers (Tnf, Ccl5, Nos2) relative to the BS only control group, no differences in expression profile of a panel of inflammatory-related soluble factors were observed between groups. A modest reduction in type I collagen was observed in the licofelone-treated group, but no meaningful differences in histologic presentation of repaired tissue were observed between groups. Furthermore, no differences in end organ functional capacity were observed between groups. Moving forward, efforts related to modulating the wound healing environment of VML should focus on polypharmaceutical strategies that target multiple aspects of the early pathophysiology of VML so as to provide an environment that is sufficiently permissive for local regenerative therapies to promote restoration of myofiber number.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Male ; Pyrroles/pharmacology ; Pyrroles/therapeutic use ; Rats ; Rats, Sprague-Dawley ; Tissue Engineering/methods ; Tissue Scaffolds/standards
Chemical Substances	Anti-Inflammatory Agents ; Pyrroles ; licofelone (P5T6BYS22Y)
Language	English
Publishing date	2021-04-14
Publishing country	Germany
Document type	Journal Article
ZDB-ID	125067-x
ISSN	1432-0878 ; 0302-766X
ISSN (online)	1432-0878
ISSN	0302-766X
DOI	10.1007/s00441-021-03449-0
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