Impact of diabetes on outcomes in breast reconstruction: A systematic review and meta-analysis.

BACKGROUND: As rates of breast cancer and type II diabetes increase, so does the number of women with diabetes undergoing breast reconstruction (BR). Patients with diabetes are at increased risk of postoperative complications. This meta-analysis seeks to evaluate the post-operative outcomes of women with diabetes who underwent BR following mastectomy. METHOD: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The EMBASE, PUBMED, and MEDLINE electronic databases were searched from inception to November 1, 2020 for studies published in English. Outcomes evaluated were overall complications, surgical complications, and longer hospital stay. Subgroup analysis investigated outcomes, such as implant/flap failure, infection, and necrosis. RESULTS: Sixty-five studies met our inclusion criteria and 38 provided data to be included in the meta-analysis. A total of 151,585 patients were included, of which 9299 had diabetes. Women with diabetes were more likely to experience overall complications (11.6% vs 5.6%; p<0.0001) and surgical complications (7.7% vs 3.3%; p<0.0001), and were more likely to have a prolonged hospital stay (p = 0.04) than women without diabetes. Subgroup analysis showed that implant loss (2.5% vs 1.6%; p = 0.0003), infection (6.8% vs 2.5%; p<0.0001) and necrosis (23.8% vs 6.5; p = 0.001) were significantly higher in women with diabetes. CONCLUSIONS: This study provides evidence that diabetes mellitus increases the risk of complications in patients with breast cancer undergoing BR after mastectomy. Prospective studies are required to establish whether diabetes that is well-controlled prior to reconstruction, including diabetes that is paired with adjuvant radiation therapy, reduces the perioperative risks.

Loss of ARNT in skeletal muscle limits muscle regeneration in aging.

The ability of skeletal muscle to regenerate declines significantly with aging. The expression of aryl hydrocarbon receptor nuclear translocator (ARNT), a critical component of the hypoxia signaling pathway, was less abundant in skeletal muscle of old (23-25 months old) mice. This loss of ARNT was associated with decreased levels of Notch1 intracellular domain (N1ICD) and impaired regenerative response to injury in comparison to young (2-3 months old) mice. Knockdown of ARNT in a primary muscle cell line impaired differentiation in vitro. Skeletal muscle-specific ARNT deletion in young mice resulted in decreased levels of whole muscle N1ICD and limited muscle regeneration. Administration of a systemic hypoxia pathway activator (ML228), which simulates the actions of ARNT, rescued skeletal muscle regeneration in both old and ARNT-deleted mice. These results suggest that the loss of ARNT in skeletal muscle is partially responsible for diminished myogenic potential in aging and activation of hypoxia signaling holds promise for rescuing regenerative activity in old muscle.

In Situ Printing of Adhesive Hydrogel Scaffolds for the Treatment of Skeletal Muscle Injuries.

Reconstructive surgery remains inadequate for the treatment of volumetric muscle loss (VML). The geometry of skeletal muscle defects in VML injuries varies on a case-by-case basis. Three-dimensional (3D) printing has emerged as one strategy that enables the fabrication of scaffolds that match the geometry of the defect site. However, the time and facilities needed for imaging the defect site, processing to render computer models, and printing a suitable scaffold prevent immediate reconstructive interventions post-traumatic injuries. In addition, the proper implantation of hydrogel-based scaffolds, which have generated promising results in vitro, is a major challenge. To overcome these challenges, a paradigm is proposed in which gelatin-based hydrogels are printed directly into the defect area and cross-linked in situ. The adhesiveness of the bioink hydrogel to the skeletal muscles was assessed ex vivo. The suitability of the in situ printed bioink for the delivery of cells is successfully assessed in vitro. Acellular scaffolds are directly printed into the defect site of mice with VML injury, exhibiting proper adhesion to the surrounding tissue and promoting remnant skeletal muscle hypertrophy. The developed handheld printer capable of 3D in situ printing of adhesive scaffolds is a paradigm shift in the rapid yet precise filling of complex skeletal muscle tissue defects.