Faculty Bibliography

OBJECTIVES/OBJECTIVE:The presence of a donor-specific positive crossmatch has been considered to be a contraindication to kidney transplantation because of the risk of hyperacute rejection. Desensitization is the process of removing hazardous preformed donor-specific antibody (DSA) in order to safely proceed with transplant. Traditionally, this involves plasmapheresis and intravenous immune globulin treatments that occur over days to weeks, and has been feasible when there is a living donor and the date of the transplant is known, allowing time for pre-emptive treatments. For sensitized patients without a living donor, transplantation has been historically difficult. SUMMARY OF BACKGROUND DATA/BACKGROUND:IdeS (imlifidase) is an endopeptidase derived from Streptococcus pyogenes which has specificity for human IgG, and when infused intravenously results in rapid cleavage of IgG. METHODS:Here we present our single-center's experience with 7 highly sensitized (cPRA98-100%) kidney transplant candidates who had DSA resulting in positive crossmatches with their donors (5 deceased, 2 living) who received IdeS within 24 hours prior to transplant. RESULTS:All pre-IdeS crossmatches were positive and would have been prohibitive for transplantation. All crossmatches became negative post-IdeS and the patients underwent successful transplantation. Three patients had DSA rebound and antibody-mediated rejection, which responded to standard of care therapies. Three patients had delayed graft function, which ultimately resolved. No serious adverse events were associated with IdeS. All patients have functioning renal allografts at a median follow-up of 235 days. CONCLUSION/CONCLUSIONS:IdeS may represent a groundbreaking new method of desensitization for patients who otherwise might have no hope for receiving a lifesaving transplant.

Background/UNASSIGNED:Donor-specific antibodies (DSA) to human leukocyte antigen increase the risk of accelerated rejection and allograft damage and reduce the likelihood of successful transplantation. Patients with full-thickness facial burns may benefit from facial allotransplantation. However, they are at a high risk of developing DSA due to standard features of their acute care. Case Presentation/UNASSIGNED:A 41-year-old male with severe disfigurement from facial burns consented to facial allotransplantation in 2014; panel reactive antibody score was 0%. In August of 2015, a suitable donor was found. Complement-dependent cytotoxicity crossmatch was negative; flow cytometry crossmatch was positive to donor B cells. An induction immunosuppression strategy consisting of rabbit antithymocyte globulin, rituximab, tacrolimus, mycophenolate mofetil (MMF), and methylprednisolone taper was designed. Total face, scalp, eyelid, ears, and skeletal subunit allotransplantation was performed without operative, immunological, or infectious complications. Maintenance immunosuppression consists of tacrolimus, MMF, and prednisone. As of posttransplant month 24, the patient has not developed acute rejection or metabolic or infectious complications. Conclusions/UNASSIGNED:To our knowledge, this is the first report of targeted B cell agents used for induction immunosuppression in skin-containing vascularized composite tissue allotransplantation. A cautious approach is warranted, but early results are promising for reconstructive transplant candidates given the exceptionally high rate of acute rejection episodes, particularly in the first year, in this patient population.

: 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