Characterization of Metacarpal Fractures in a Military Population.

The purpose of this study was to investigate the incidence and type of metacarpal (MC) fractures in a military population, and whether these fractures are related to age, military occupational specialty, aggression, or accidental injury. A retrospective record-based review was conducted at a single military center over a 5-year period. Service members with index finger through small finger MC fracture were identified. Data were collected utilizing Armed Forces Health Longitudinal Technology Application and electronic profile (e-profile) databases. Data collected included demographic information, mechanism of injury, nature of injury, total number of visits, and estimated time on physical restriction. 400 patients met inclusion criteria. Males accounted for 94% of the study population, 75% of fractures were of the small finger MC, 54% of patients were between 20 and 24 years, 90% were sustained by junior enlisted personnel, and most occurred by punching. Men aged <25 years were more likely to have intentional injuries. Total time on limited duty profile averaged 38 days and the average medically nondeployable profile was 26 days. MC fractures most commonly affect young, male, junior enlisted service members and are often self-inflicted. As a result, these injuries account for time lost at work, reduced job performance, and decreased medical readiness.

Mesenchymal progenitor cells derived from traumatized muscle enhance neurite growth.

The success of peripheral nerve regeneration is governed by the rate and quality of axon bridging and myelination that occurs across the damaged region. Neurite growth and the migration of Schwann cells is regulated by neurotrophic factors produced as the nerve regenerates, and these processes can be enhanced by mesenchymal stem cells (MSCs), which also produce neurotrophic factors and other factors that improve functional tissue regeneration. Our laboratory has recently identified a population of mesenchymal progenitor cells (MPCs) that can be harvested from traumatized muscle tissue debrided and collected during orthopaedic reconstructive surgery. The objective of this study was to determine whether the traumatized muscle-derived MPCs exhibit neurotrophic function equivalent to that of bone marrow-derived MSCs. Similar gene- and protein-level expression of specific neurotrophic factors was observed for both cell types, and we localized neurogenic intracellular cell markers (brain-derived neurotrophic factor and nestin) to a subpopulation of both MPCs and MSCs. Furthermore, we demonstrated that the MPC-secreted factors were sufficient to enhance in vitro axon growth and cell migration in a chick embryonic dorsal root ganglia (DRG) model. Finally, DRGs in co-culture with the MPCs appeared to increase their neurotrophic function via soluble factor communication. Our findings suggest that the neurotrophic function of traumatized muscle-derived MPCs is substantially equivalent to that of the well-characterized population of bone marrow-derived MPCs, and suggest that the MPCs may be further developed as a cellular therapy to promote peripheral nerve regeneration.

Inducible expression of neurotrophic factors by mesenchymal progenitor cells derived from traumatically injured human muscle.

Peripheral nerve damage frequently accompanies musculoskeletal trauma and repair of these nerves could be enhanced by the targeted application of neurotrophic factors (NTFs), which are typically expressed by endogenous cells that support nerve regeneration. Injured muscle tissues express NTFs to promote reinnervation as the tissue regenerates, but the source of these factors from within the muscles is not fully understood. We have previously identified a population of mesenchymal progenitor cells (MPCs) in traumatized muscle tissue with properties that support tissue regeneration, and our hypothesis was that MPCs also secrete the NTFs that are associated with muscle tissue reinnervation. We determined that MPCs express genes associated with neurogenic function and measured the protein-level expression of specific NTFs with known functions to support nerve regeneration. We also demonstrated the effectiveness of a neurotrophic induction protocol to enhance the expression of the NTFs, which suggests that the expression of these factors may be modulated by the cellular environment. Finally, neurotrophic induction affected the expression of cell surface markers and proliferation rate of the MPCs. Our findings indicate that traumatized muscle-derived MPCs may be useful as a therapeutic cell type to enhance peripheral nerve regeneration following musculoskeletal injury.

Cytokine expression in muscle following traumatic injury.

Heterotopic ossification (HO) occurs at a high frequency in severe orthopaedic extremity injuries; however, the etiology of traumatic HO is virtually unknown. Osteogenic progenitor cells have previously been identified within traumatized muscle. Although the signaling mechanisms that lead to this dysregulated differentiation pathway have not been identified, it is assumed that inflammation and fibrosis, which contribute to an osteoinductive environment, are necessary for the development of HO. The hypothesis of this study was that cytokines related to chronic inflammation, fibrogenesis, and osteogenesis become up-regulated following severe muscle trauma where HO forms. Classification of these cytokines by their differential expression relative to control muscle will provide guidance for further study of the mechanisms leading to HO. Real-time RT-PCR analysis revealed no significant up-regulation of cytokines typically associated with HO (e.g., BMP-4, as observed in the genetic form of HO, fibrodysplasia ossificans progressiva). Instead, the cytokine gene expression profile associated with the traumatized muscle included up-regulation of cytokines associated with osteogenesis and fibrosis (i.e., BMP-1 and TGF-ß(1)). Using immunohistochemistry, these cytokines were localized to fibroproliferative lesions, which have previously been implicated in HO. This study identifies other cell and tissue-level interactions in traumatized muscle that should be investigated further to better define the etiology of HO.

Putative heterotopic ossification progenitor cells derived from traumatized muscle.

Heterotopic ossification (HO) is a frequent complication following combat-related trauma, but the pathogenesis of traumatic HO is poorly understood. Building on our recent identification of mesenchymal progenitor cells (MPCs) in traumatically injured muscle, the goal of this study was to evaluate the osteogenic potential of the MPCs in order to assess the role of these cells in HO formation. Compared to bone marrow-derived mesenchymal stem cells (MSCs), a well-characterized population of osteoprogenitor cells, the MPCs exhibited several significant differences during osteogenic differentiation and in the expression of genes related to osteogenesis. Upon osteogenic induction, MPCs showed increased alkaline phosphatase activity, production of a mineralized matrix, and up-regulated expression of the osteoblast-associated genes CBFA1 and alkaline phosphatase. However, MPCs did not appear to reach terminal differentiation as the expression of osteocalcin was not substantially up-regulated. With the exception of a few genes, the osteogenic gene expression profile of traumatized muscle-derived MPCs was comparable to that of the MSCs after osteogenic induction. These findings indicate that traumatized muscle-derived MPCs have the potential to function as osteoprogenitor cells when exposed to the appropriate biochemical environment and are the putative osteoprogenitor cells that initiate ectopic bone formation in HO.

Use of stored serum from Uganda for development and evaluation of a human immunodeficiency virus type 1 testing algorithm involving multiple rapid immunoassays.

We report the development and evaluation of a human immunodeficiency virus type 1 testing algorithm consisting of three rapid antibody detection tests. Stored serum samples from Uganda were utilized with a final algorithm sensitivity of 100% and a specificity of 98.9% (95% confidence interval, 98.6% to 99.3%).