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Background Multipotent progenitor cells have been harvested from different human tissues, including the bone marrow, adipose tissue, and umbilical cord blood. Previously, we identified a population of mesenchymal progenitor cells (MPCs) isolated from the traumatized muscle of patients undergoing reconstructive surgery following a war-related blast injury. These cells demonstrated the ability to differentiate into multiple mesenchymal lineages. While distal radius fractures from a civilian setting have a much lower injury mechanism (low-energy trauma), we hypothesized that debrided traumatized muscle near the fracture site would contain multipotent progenitor cells with the ability to differentiate and regenerate the injured tissue. Methods The traumatized muscle was debrided from the pronator quadratus in patients undergoing open reduction and internal fixation for a distal radius fracture at the Walter Reed National Military Medical Center. Using a previously described protocol for the isolation of MPCs from war-related extremity injuries, cells were harvested from the low-energy traumatized muscle samples and expanded in culture. Isolated cells were characterized by flow cytometry and q-RT-PCRs and induced to adipogenic, osteogenic, and chondrogenic differentiation. Downstream analyses consisted of lineage-specific staining and q-RT-PCR. Results Cells isolated from low-energy traumatized muscle samples were CD73+, CD90+, and CD105+ that are the characteristic of adult human mesenchymal stem cells. These cells expressed high levels of the stem cell markers OCT4 and NANOG 1-day after isolation, which was dramatically reduced over-time in monolayer culture. Following induction, lineage-specific markers were demonstrated by each specific staining and confirmed by gene expression analysis, demonstrating the ability of these cells to differentiate into adipogenic, osteogenic, and chondrogenic lineages. Conclusions Adult multipotent progenitor cells are an essential component for the success of regenerative medicine efforts. While MPCs have been isolated and characterized from severely traumatized muscle from high-energy injuries, here, we report that cells with similar characteristics and multipotential capacity have been isolated from the tissue that was exposed to low-energy, community trauma.

Background: Patellar tendon ruptures have a reported incidence of 0.68 per 100,000 person-years in the general population. The epidemiology of surgically treated patellar tendon ruptures in the US military has yet to be reported, which would provide opportunity for identification of risk factors for these otherwise healthy and active patients. Purpose: To determine the incidence of patellar tendon rupture in the Military Health System (MHS) population and to analyze demographic patterns, surgical fixation methods, and rerupture rates. Study Design: Case-control study; Level of evidence, 3. Methods: We utilized the MHS Data Repository (MDR) to identity active-duty military servicemembers surgically treated for patellar tendon rupture between 2010 and 2015. Records were reviewed for demographic information, injury characteristics, fixation technique, and occurrence of rerupture. Risk factors for rupture were calculated using Poisson regression based on population counts and demographic data obtained in the MDR. Risk factors for rerupture and return to duty were analyzed via univariate analysis and multivariate regression. Results: A total of 504 operatively treated primary patellar tendon repairs in 483 patients were identified, with an overall incidence of 6 per 100,000 person-years. Mean age was 33.6 years (range, 17-54 years) and 98% of patients were male. Fixation method was 81% bone tunnels and 7% suture anchors, and 12% were unknown. Black race had a higher relative rate ratio for rupture compared with the race categories White (9.21; P < .0001) and Other (3.27; P < .0001). The rupture rate was higher in 35- to 44-year-old patients compared with those aged 18 to 24 years ( P < .0001), 25 to 34 years ( P < .0001), and 45 to 64 years ( P = .004). Return to full previous level of activity occurred in 75.8% of patients, 14.6% returned to activity with limitations, and 9.5% were medically separated. The rerupture rate was 3%. Fixation method, tobacco usage, body mass index, and race were not significant risk factors for rerupture. Conclusion: The incidence of patellar tendon rupture in the US military population is substantially higher than has been reported in the civilian population. Among military personnel, men, Black servicemembers, and those aged 35 to 44 years were at highest risk for patellar tendon rupture. Three-quarters of patients were able to return to full activity without limitations. The rerupture rate was low and unaffected by fixation method.

Peripheral Nerve Injury (PNI) represents a major clinical and economic burden. Despite the ability of peripheral neurons to regenerate their axons after an injury, patients are often left with motor and/or sensory disability and may develop chronic pain. Successful regeneration and target organ reinnervation require comprehensive transcriptional changes in both injured neurons and support cells located at the site of injury. The expression of most of the genes required for axon growth and guidance and for synapsis formation is repressed by a single master transcriptional regulator, the Repressor Element 1 Silencing Transcription factor (REST). Sustained increase of REST levels after injury inhibits axon regeneration and leads to chronic pain. As targeting of transcription factors is challenging, we tested whether modulation of REST activity could be achieved through knockdown of carboxy-terminal domain small phosphatase 1 (CTDSP1), the enzyme that stabilizes REST by preventing its targeting to the proteasome. To test whether knockdown of CTDSP1 promotes neurotrophic factor expression in both support cells located at the site of injury and in peripheral neurons, we transfected mesenchymal progenitor cells (MPCs), a type of support cells that are present at high concentrations at the site of injury, and dorsal root ganglion (DRG) neurons with REST or CTDSP1 specific siRNA. We quantified neurotrophic factor expression by RT-qPCR and Western blot, and brain-derived neurotrophic factor (BDNF) release in the cell culture medium by ELISA, and we measured neurite outgrowth of DRG neurons in culture. Our results show that CTDSP1 knockdown promotes neurotrophic factor expression in both DRG neurons and the support cells MPCs, and promotes DRG neuron regeneration. Therapeutics targeting CTDSP1 activity may, therefore, represent a novel epigenetic strategy to promote peripheral nerve regeneration after PNI by promoting the regenerative program repressed by injury-induced increased levels of REST in both neurons and support cells.

Background: Peripheral Nerve Injury (PNI) represents a major clinical and economic burden. Despite the ability of peripheral neurons to regenerate their axons after an injury, patients are often left with motor and/or sensory disability and may develop chronic pain. Successful regeneration and target organ reinnervation require comprehensive transcriptional changes in both injured neurons and support cells located at the site of injury. The expression of most of the genes required for axon growth and guidance and for synapsis formation is repressed by a single master transcriptional regulator, the Repressor Element 1 Silencing Transcription factor (REST). Sustained increase of REST levels after injury inhibits axon regeneration and leads to chronic pain. REST is stabilized by the Carboxy-terminal domain small phosphatase 1 (CTDSP1), which prevents REST targeting to the proteasome. Here, we explore whether knockdown of CTDSP1 promotes neurotrophic factor expression in mesenchymal progenitor cells (MPCs), a type of support cells that can be harvested from the site of injury during surgical debridement, and in dorsal root ganglion (DRG) neurons. In addition, we explore whether CTDSP1 knockdown supports DRG neurite regeneration. Methods: Cultured human MPCs or rat DRG neurons were transfected with REST or CTDSP1 specific siRNA. Neurotrophic factor expression was analyzed by RT-qPCR and Western Blot. Brain-derived Neurotrophic Factor (BDNF) in cell culture medium was quantified by ELISA. Axon regeneration was quantified measuring the length of the longest neurite of a neuron. Results: Knockdown of REST or CTDSP1 in MPCs results in increased expression of BDNF and nerve growth factor (NGF). In addition, knockdown of CTDSP1 leads to increased release of BDNF in cell culture medium from MPCs and to reduced levels of REST protein. Finally, knockdown of CTDSP1 in DRG neurons results in increased levels of BDNF and increased DRG neurite growth rate.Conclusions: CTDSP1 knockdown promotes neurotrophic factor expression in both DRG neurons and the support cells MPCs. In addition, it promotes DRG neuron regeneration. Therapeutics targeting CTDSP1 activity may represent a novel epigenetic strategy to promote peripheral nerve regeneration after PNI by promoting the regenerative program repressed by injury-induced increased levels of REST in both neurons and support cells.

Animal studies are essential to biomedical research and the cornerstone is a reproducible animal model. While there are many reports on rodent peripheral nerve injury models, a large animal model is essential to confirm the effects of nerve regeneration over the longer distances of regeneration required in humans. Swine have long been used as a large animal model for other surgical and biomedical studies. This paper represents a novel neurovascular injury model in the Sus scrofa domesticus swine (American Yorkshire pig). This paper will describe our experience and recommendations with pre-operative, operative and post-operative protocols and our refinements to produce an effective model.

If I Die Tonight In this poem, a surgeon reflects on civil rights activism in response to killings of black people. He touches on both family history and the complexity of being black in America.

CASE An immunocompetent 43-year-old man was diagnosed with necrotizing fasciitis of his forearm. Despite receiving appropriate treatment, his clinical condition continued to deteriorate. Further evaluation revealed subsequent proliferation of the infection to multiple noncontiguous areas of the body consistent with a rare condition known as synchronous multifocal necrotizing fasciitis. Prompt identification, followed by serial debridements of all affected areas, ultimately saved the patient's life. CONCLUSION This unusual multifocal presentation of necrotizing fasciitis can produce diagnostic uncertainty and delay life-saving treatment. Early recognition, followed by prompt treatment, is paramount for reducing morbidity and mortality associated with this devastating infection.