Faculty Bibliography

BACKGROUND:Facial transplantation introduced a paradigm shift in the reconstruction of extensive facial defects. Although the feasibility of the procedure is well established, new challenges face the field in its second decade. METHODS:The authors' team has successfully treated patients with extensive thermal and ballistic facial injuries with allotransplantation. The authors further validate facial transplantation as a reconstructive solution for irreparable facial injuries. Following informed consent and institutional review board approval, a partial face and double jaw transplantation was performed in a 25-year-old man who sustained ballistic facial trauma. Extensive team preparations, thorough patient evaluation, preoperative diagnostic imaging, three-dimensional printing technology, intraoperative surgical navigation, and the use of dual induction immunosuppression contributed to the success of the procedure. RESULTS:The procedure was performed on January 5 and 6, 2018, and lasted nearly 25 hours. The patient underwent hyoid and genioglossus advancement for floor-of-mouth dehiscence, and palate wound dehiscence repair on postoperative day 11. Open reduction and internal fixation of left mandibular nonunion were performed on postoperative day 108. Nearly 1 year postoperatively, the patient demonstrates excellent aesthetic outcomes, intelligible speech, and is tolerating an oral diet. He remains free from acute rejection. CONCLUSIONS:The authors validate facial transplantation as the modern answer to the classic reconstructive challenge imposed by extensive facial defects resulting from ballistic injury. Relying on a multidisciplinary collaborative approach, coupled with innovative emerging technologies and immunosuppression protocols, can overcome significant challenges in facial transplantation and reinforce its position as the highest rung on the reconstructive ladder. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Therapeutic, V.

Thoracic aortic aneurysm (TAA) is a complex life-threatening disease characterized by extensive extracellular matrix (ECM) fragmentation and persistent inflammation, culminating in a weakened aorta. Although evidence suggests defective canonical signaling pathways in TAA, the full spectrum of mechanisms contributing to TAA is poorly understood, therefore limiting the scope of drug-based treatment. Here, we used a sensitive RNA sequencing approach to profile the transcriptomic atlas of human TAA. Pathway analysis revealed upregulation of key matrix-degrading enzymes and inflammation coincident with the axonal guidance pathway. We uncovered their novel association with TAA and focused on the expression of Semaphorins and Netrins. Comprehensive analysis of this pathway showed that several members were differentially expressed in TAA compared to controls. Immunohistochemistry revealed that Semaphorin4D and its receptor PlexinB1, similar to Netrin-1 proteins were highly expressed in damaged areas of TAA tissues but faintly detected in the vessel wall of non-diseased sections. It should be considered that the current study is limited by its sample size and the use of internal thoracic artery as control for TAA for the sequencing dataset. Our data determines important neuronal regulators of vascular inflammatory events and suggest Netrins and Semaphorins as potential key contributors of ECM degradation in TAA.

Background/UNASSIGNED:Perioperative cardiovascular outcomes of transplant surgery are not well defined. We evaluated the incidence of perioperative major cardiovascular and cerebrovascular events (MACCE) after non-cardiac transplant surgery from a large database of hospital admissions from the United States. Methods/UNASSIGNED:Patients ≥18 years of age undergoing non-cardiac solid organ transplant surgery from 2004 to 2014 were identified from the Healthcare Cost and Utilization Project's (HCUP) National Inpatient Sample (NIS). The primary outcome was perioperative MACCE, defined as in-hospital death, myocardial infarction (MI), or ischemic stroke. Results/UNASSIGNED:A total of 49,978 hospitalizations for transplant surgery were identified. Renal (67.3%), liver (21.6%), and lung (6.7%) transplantation were the most common surgeries. Perioperative MACCE occurred in 1,539 transplant surgeries (3.1%). Recipients of organ transplantation were more likely to have perioperative MACCE in comparison to non-transplant, non-cardiac surgery (3.1% vs. 2.0%, p < 0.001; adjusted OR [aOR] 1.29, 95% CI 1.22-1.36). MACCE after transplant surgery were driven by increased mortality (1.7% vs. 1.1%, p < 0.001; aOR 1.15, 95% CI 1.07-1.23) and MI (1.2% vs. 0.6%, p < 0.001; aOR 2.26, 95% CI 2.09-2.46) versus non-transplant surgery, with lower rates of stroke (0.3% vs. 0.5%, p < 0.001; aOR 0.56, 95% CI 0.47-0.65). Among patients hospitalized for renal, liver, and lung transplantation, MACCE occurred in 1.7%, 5.6%, and 7.5%, respectively, with no difference in the frequency of MI by surgery type. Conclusions/UNASSIGNED:Cardiovascular outcomes of transplant surgery vary by surgical subtype and are largely driven by increased perioperative death and MI. Efforts to reduce cardiovascular risks of non-cardiac organ transplant surgery are necessary.

Kidneys from donors with blood type A2 can be successfully transplanted into blood type B and O recipients without the need for desensitization if the recipient's starting anti-A hemagglutinin titer is within an acceptable range. National kidney allocation policy now offers priority for eligible B recipients to receive A2 or A2B deceased donor kidneys, and therefore, the frequency with which A2 or A2B to B transplants will occur is expected to increase. The precise mechanisms by which antibody-mediated rejection is averted in these cases despite the presence of both circulating anti-A antibody and expression of the A2 antigen on the graft endothelium are not known. Whether this process mirrors proposed mechanisms of accommodation, which can occur in recipients of ABO incompatible transplants, is also not known. Repeated exposure to mismatched antigens after retransplantation could elicit memory responses resulting in antibody rebound and accelerated antibody-mediated rejection. Whether this would occur in the setting of repeated A2 donor exposure was uncertain. Here we report the case of a patient with history of a prior A2 to B transplant which failed owing to nonimmunologic reasons; the patient successfully underwent a repeat A2 to B transplant. Neither rebound in anti-A2 antibody nor clinical evidence of antibody-mediated rejection were observed after the transplant. Current kidney allocation will likely enable more such transplants in the future, and this may provide a unique patient population in whom the molecular mechanisms of incompatible graft accommodation may be investigated.

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.

: 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.