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Introduction Hand and digit replantations can be complicated by vascular insufficiency necessitating revision of the original replantation. To date, few studies have evaluated outcomes in secondary revascularizations following replantation. Therefore, the objective of this study was to evaluate the incidence, etiology, and survival rates following secondary revascularization after hand and digit replantations. Materials and Methods A literature search was performed on NCBI for studies documenting secondary revascularization procedures following hand and digit replant. Studies were evaluated for the etiology of vascular failure, frequency of secondary revascularization, and survival rates following intervention. Statistical analysis was conducted across the pooled dataset. Results A total of 16 studies including 1,192 amputations were analyzed. We found that 16.9% (201/1,192) of replants were complicated by vascular compromise. The frequency of vascular compromise was not statistically different between arterial and venous etiologies. The survival rate following secondary revascularization was 55.6%, with no significant difference between the arterial and venous groups. Secondary arterial revascularization was often treated with arterial revision (nine of nine studies) and/or with vein grafting (two of nine studies). Secondary revascularization for venous insufficiency resulted in different survival rates for nonsurgical modalities (58%) versus vein revision (37.5%) versus vein grafting (100%). Conclusion Survival rates following secondary revascularization are lower; however, they may be improved using vein grafts following venous insufficiency. These data can be used to better understand the etiology of replant failure and guide decision-making.

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INTRODUCTION: Extracellular vesicles (EVs) are cell-secreted packages that deliver cargo to target cells to effect functional and phenotypic changes. They are secreted by many different cell types, including adipose-derived stem cells (ADSCs), which are a promising field of study in regenerative medicine. Our aim was to perform a systematic review of the literature to summarize the scientific work that has been conducted on ADSC EVs to date. METHODS: The Pubmed database was queried with keywords (and variations of) "adipose derived stem cell," "stromal vascular fraction," and "extracellular vesicles." We excluded review papers, then manually screened articles based on title and abstract. Full-text articles were assessed for eligibility to include in final review. RESULTS: While an extensive body of research exists on EVs, a much smaller proportion of that is original research on ADSC EVs. Of 44 manuscripts that met our database search criteria, 21 articles were selected for our systematic review. CONCLUSION: ADSC EVs were found to exert effects on angiogenesis, cell survival and apoptosis, inflammation, tissue regeneration, and reduction of disease pathology. Further studies examine characteristics of ADSC EVs. Future work should aim to further detail the safety profiles of ADSC EVs given their potential for cell-based therapies. The body of research studies characterizing ADSC EVs continues to expand, and much work remains to be done before human pilot studies can be considered. To our knowledge, we offer the first systematic review summarizing the research on ADSC EVs and their determined roles to date.

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BACKGROUND: The incidence of nipple-sparing mastectomy is rising, but no single incision type has been proven to be superior. This study systematically evaluated the rate and efficacy of various nipple-sparing mastectomy incision locations, focusing on nipple-areola complex necrosis and reconstructive method. METHODS: A systematic literature review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines identifying studies on nipple-sparing mastectomy where incision type was described. Pooled descriptive statistics meta-analysis of overall (nipple-areola complex) necrosis rate and nipple-areola complex necrosis by incision type was performed. RESULTS: Fifty-one studies (9975 nipple-sparing mastectomies) were included. Thirty-two incision variations were identified and categorized into one of six groups: inframammary fold, radial, periareolar, mastopexy/prior scar/reduction, endoscopic, and other. The most common incision types were inframammary fold [3634 nipple-sparing mastectomies (37.8 percent)] and radial [3575 nipple-sparing mastectomies (37.2 percent)]. Meta-analysis revealed an overall partial nipple-areola complex necrosis rate of 4.62 percent (95 percent CI, 3.14 to 6.37 percent) and a total nipple-areola complex necrosis rate of 2.49 percent (95 percent CI, 1.87 to 3.21 percent). Information on overall nipple-areola complex necrosis rate by incision type was available for 30 of 51 studies (4645 nipple-sparing mastectomies). Periareolar incision had the highest nipple-areola complex necrosis rate (18.10 percent). Endoscopic and mastopexy/prior scar/reduction incisions had the lowest rates of necrosis at 4.90 percent and 5.79 percent, respectively, followed by the inframammary fold incision (6.82 percent). The rate of single-stage implant reconstruction increased during this period. CONCLUSIONS: For nipple-sparing mastectomy, the periareolar incision maintains the highest necrosis rate because of disruption of the nipple-areola complex blood supply. The inframammary fold incision has become the most popular incision, demonstrating an acceptable complication profile.

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The decline of tissue regenerative potential with age correlates with impaired stem cell function. However, limited strategies are available for therapeutic modulation of stem cell function during aging. Using skeletal muscle stem cells (MuSCs) as a model system, we identify cell death by mitotic catastrophe as a cause of impaired stem cell proliferative expansion in aged animals. The mitotic cell death is caused by a deficiency in Notch activators in the microenvironment. We discover that ligand-dependent stimulation of Notch activates p53 in MuSCs via inhibition of Mdm2 expression through Hey transcription factors during normal muscle regeneration and that this pathway is impaired in aged animals. Pharmacologic activation of p53 promotes the expansion of aged MuSCs in vivo. Altogether, these findings illuminate a Notch-p53 signaling axis that plays an important role in MuSC survival during activation and is dysregulated during aging, contributing to the age-related decline in muscle regenerative potential.

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Adult skeletal muscle stem cells, or satellite cells (SCs), regenerate functional muscle following transplantation into injured or diseased tissue. To gain insight into human SC (huSC) biology, we analyzed transcriptome dynamics by RNA sequencing of prospectively isolated quiescent and activated huSCs. This analysis indicated that huSCs differentiate and lose proliferative potential when maintained in high-mitogen conditions ex vivo. Further analysis of gene expression revealed that p38 MAPK acts in a transcriptional network underlying huSC self-renewal. Activation of p38 signaling correlated with huSC differentiation, while inhibition of p38 reversibly prevented differentiation, enabling expansion of huSCs. When transplanted, expanded huSCs differentiated to generate chimeric muscle and engrafted as SCs in the sublaminar niche with a greater frequency than freshly isolated cells or cells cultured without p38 inhibition. These studies indicate characteristics of the huSC transcriptome that promote expansion ex vivo to allow enhanced functional engraftment of a defined population of self-renewing huSCs.

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