Faculty Bibliography

: The first facial transplantation in 2005 ushered in a new era in reconstructive surgery, offering new possibilities for the repair of severe disfigurements previously limited by conventional techniques. Advances in allograft design, computerized preoperative planning, surgical technique, and postoperative revisions have helped push the boundaries in this new frontier of vascularized composite allotransplantation. Over the past 12 years, 40 of these procedures have been performed across the world, offering the field the opportunity to reflect on current outcomes. Successes achieved in the brief history of facial transplantation have resulted in a new set of obstacles the field must now overcome. In this review, we aim to highlight the achievements, major challenges, and future directions of this rapidly evolving field.

The non-life-saving nature of facial transplantation (FT) has raised concerns over the procurement of a facial allograft (FA) and allocated solid organs (SO) from a single donor. In response, FT teams have described their experiences performing simultaneous and asynchronous procurement. One unanimous conclusion is that the safe procurement of life-saving organs must be given priority during the donor operation

Purpose: There is a significant variation in the MELD scores and subsequent morbidity among liver recipients in the US. Larger OPOs consistently serve patients with advanced disease. Previous studies have shown 2.5 times greater prevalence of transplanted patients with MELD ³ 24 in these OPOs. CMS recent reimbursement adjustments may disproportionately affect certain programs given their increased prevalence of patients with more advanced disease. Methods: We analyzed the prevalence of transplants among patients with high UNET MELD scores and associated charges, costs, and reimbursements. We compared low, medium and high MELD score groups. Between 2014-2015, 43 liver transplants, all with >30 days survival, were analyzed. Results: Only 2 had MELD scores below 25 at transplant, both of which from live donors. 95% of patients had MELD scores above 25 and among these, 18% had MELD 40 or were Status 1. Compared to the national average, our MELD scores were: 25% 21-30 (National 21.5%, p >0.05), 70.5% 31-40 (National 25.9%, p < 0.001), and 4.5% Status 1 (National 5.9%, p >0.05). For MELD scores 21-30, hospital charges averaged $645,214 and reimbursements were $150,706. For MELD scores 31-39, charges were $686,720, and reimbursement were $139,776. Reviewing MELD 40/ Status 1 patients, the average hospital charges and reimbursements were $1,136,813 and $293,776 respectively. We compared their amounts to the MELD 40 patients who had hospital charges of $625,371 and reimbursements of $142,051 respectively. This demonstrated a loss of $843,037 for the first group and $483,320 for the second. Length of stay was 32 days for MELD 40/ Status 1 and 8 days for MELD 40 (p < 0.000). Conclusion: ³ 40 MELD patients have a huge financial impact on institutions. The difference between 25-39 and ³40 MELD points is greater than half a million dollars. These data reflect and include dialysis, intubation and ICU stay but do not include rehabilitation expenses which will be the focus of another study. We find that our institution, which likely reflects many institutions in our OPO, serves sicker patients and therefore incurs higher costs but receives lower reimbursements, as they are based on national expected care costs for healthier patients. A broader sharing in the US may equalize costs. Payers should take into account the added financial burden of performing transplant in high MELD patients

Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle-/-, and Dectin-1-/- mice. The role of C/EBPbeta and hypoxia-inducible factor-1alpha (HIF-1alpha) signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con A hepatitis. Most significantly, Mincle deletion or blockade protected against Con A hepatitis, whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other C-type lectin receptors did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-kappabeta-related signaling intermediates C/EBPbeta and HIF-1alpha, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con A hepatitis and inhibition of both C/EBPbeta and HIF-1alpha reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation.