Implications of an Altered Gut Microbiome in Rat Experimental Vascularized Composite Transplantation.

OBJECTIVES: Vascularized composite allotransplantation is a reconstructive option after severe injury but is fraught with complications, including transplant rejection due to major histocompatibility complex mismatch in the context of allogeneic transplant, which in turn is due to altered immuno-inflammation secondary to transplant. The immunosuppressant tacrolimus can prevent rejection. Because tacrolimus is metabolized predominantly by the gut, this immunosuppressant alters the gut microbiome in multiple ways, thereby possibly affecting immunoinflammation. MATERIALS AND METHODS: We performed either allogeneic or syngeneic transplant with or without tacrolimus in rats. We quantified protein-level inflammatory mediators in the skin, muscle, and plasma and assessed the diversity of the gut microbiome through 16S RNA analysis at several timepoints over 31 days posttransplant. RESULTS: Statistical analysis highlighted a complex interaction between major histocompatibility complex and tacrolimus therapy on the relative diversity of the microbiome. Time-interval principal component analysis indicated numerous significant differences in the tissue characteristics of inflammation and gut microbiome that varied over time and across experimental conditions. Classification and regression tree analysis suggested that both inflammatory mediators in specific tissues and changes in the gut microbiome are useful in characterizing the temporal dynamics of posttransplant inflammation. Dynamic network analysis highlighted unique changes in Methanosphaera that were correlated with Peptococcusin allogeneic transplants with and without tacrolimus versus Prevotella in syngeneic transplant with tacrolimus, suggesting that alterations in Methanosphaera might be a biomarker of vascularized composite allotransplant rejection. CONCLUSIONS: Our results suggest a complex interaction among major histocompatibility complex, local and systemic immuno-inflammation, and tacrolimus therapy and highlight the potential for novel insights into vascularized composite allotransplant from computational approaches.

Robotic Surgery and Hospital Reimbursement.

The field of plastic surgery remains at the forefront of technological and surgical innovation. However, the promising applications of robotics in plastic surgery must be thoughtfully balanced with hospital finances and reimbursements. Robotic systems have been studied extensively across multiple surgical disciplines and across diverse health care systems. The results show that there may be equal or better patient outcomes than alternatives. In an era where fiscal responsibility in health care is a top priority, thoughtful budgeting and spending must be considered and revisited frequently to attain sustainable organizational models that ensure appropriate use of robotic technology.

In situ recruitment of regulatory T cells promotes donor-specific tolerance in vascularized composite allotransplantation.

Vascularized composite allotransplantation (VCA) encompasses face and limb transplantation, but as with organ transplantation, it requires lifelong regimens of immunosuppressive drugs to prevent rejection. To achieve donor-specific immune tolerance and reduce the need for systemic immunosuppression, we developed a synthetic drug delivery system that mimics a strategy our bodies naturally use to recruit regulatory T cells (Treg) to suppress inflammation. Specifically, a microparticle-based system engineered to release the Treg-recruiting chemokine CCL22 was used in a rodent hindlimb VCA model. These "Recruitment-MP" prolonged hindlimb allograft survival indefinitely (>200 days) and promoted donor-specific tolerance. Recruitment-MP treatment enriched Treg populations in allograft skin and draining lymph nodes and enhanced Treg function without affecting the proliferative capacity of conventional T cells. With implications for clinical translation, synthetic human CCL22 induced preferential migration of human Treg in vitro. Collectively, these results suggest that Recruitment-MP promote donor-specific immune tolerance via local enrichment of suppressive Treg.