OPTN/SRTR 2022 Annual Data Report: Vascularized Composite Allograft.

This year's chapter on vascularized composite allograft (VCA) encompasses reviews of data collected from 2014 (when VCA was included in the Final Rule) through 2022. The present Annual Data Report shows that the number of VCA recipients in the United States continues to be small and has remained consistent from the prior report. The data continue to be limited by sample size, with trends persistently demonstrating a predominance of White males in the young/middle-aged population as both donors and recipients for nonuterus VCA transplants, and White women younger than 35 years as the predominant recipients of uterus transplant. Similar to the 2021 report, there were only eight failed uterus grafts and one failed nonuterus VCA graft reported from 2014 through 2022. Standardization of definitions of success and failure as well as outcome measures for the different VCA types remain unmet needs in VCA transplantation.

Banff 2022 Vascularized Composite Allotransplantation Meeting Report: Diagnostic criteria for vascular changes.

As more data become available, the Banff 2007 working classification of skin-containing vascularized composite allograft (VCA) pathology is expected to evolve and develop. This report represents the Banff VCA Working Group's consensus on the first revision of the 2007 scoring system. Prior to the 2022 Banff-CanXadian Society of Transplantation Joint Meeting, 83 clinicians and/or researchers were invited to a virtual meeting to discuss whether the 2007 Banff VCA system called for a revision. Unanimously, it was determined that the vascular changes were to be included in the first revision. Subsequently, 2 international online surveys, each followed by virtual discussions, were launched. The goals were (1) to identify which changes define severe rejection, (2) to grade their importance in the evaluation of severe rejection, and (3) to identify emerging criteria to diagnose rejection. A final hybrid (in-person and virtual) discussion at the Banff/Canadian Society of Transplantation Joint Meeting finalized the terminology, the definition, a scoring system, and a reporting system of the vascular changes. This proposal represents an international consensus on this topic and establishes the first revision of the Banff 2007 working classification of skin-containing vascularized composite allograft pathology.

OPTN/SRTR 2021 Annual Data Report: Vascularized Composite Allograft.

Year 2020 marked the first OPTN/SRTR Annual Data Report that included a chapter on vascularized composite allograft (VCA), which encompassed reviews of data collected between 2014 (when VCA was included in the Final Rule) and 2020. The present Annual Data Report shows that the number of VCA recipients in the United States continues to be small and trended downward in 2021. While data continue to be limited by sample size, trends continue to show a predominance in White, young/middle-aged, male recipients. Similar to the 2020 report, eight uterus and one non-uterus VCA graft failures were reported from 2014 through 2021. Critical to advancement of VCA transplantation will be the standardization of definitions, protocols, and outcome measures for the different VCA types. Like intestinal transplants, it is likely that VCA transplants will be concentrated and performed at referral transplant centers.

American Society of Transplant Surgeons-American Society of Transplantation report of FDA meeting on regulatory expectations for xenotransplantation products.

In June 2022, the US Food and Drug Administration Center for Biologics Evaluation and Research held the 73rd meeting of the Cellular, Tissue, and Gene Therapies Advisory Committee for public discussion of regulatory expectations for xenotransplantation products. The members of a joint American Society of Transplant Surgeons/American Society of Transplantation committee on xenotransplantation compiled a meeting summary focusing on 7 topics believed to be key by the committee: (1) preclinical evidence supporting progression to a clinical trial, (2) porcine kidney function, (3) ethical aspects, (4) design of initial clinical trials, (5) infectious disease issues, (6) industry perspectives, and (7) regulatory oversight.

Plastic Surgery Diversity through the Decade: Where We Stand and How We Can Improve.

Several studies over the past decade have investigated diversity within the field of plastic surgery, yet it remains unclear if an increase has resulted. This study sought to review the status of diversity within plastic surgery over the last decade and form strategies for residency programs to increase diversity recruitment. METHODS: Data analysis of racial demographics from the Association of American Medical Colleges databases was completed for all medical students, integrated plastic surgery residency applicants, integrated plastic surgery residents, and academic faculty from 2010 to 2020. Proportional averages were analyzed comparing 5 year durations with heteroscedastic t-tests. Interviews were then conducted with medical school diversity and inclusion officers across the country and subsequent thematic analysis was completed. Finally, diversity recruitment recommendations were synthesized from interview data. RESULTS: There was no significant change in demographics of integrated plastic surgery applicants between 2010-2014 and 2015-2020. The only significant finding among integrated plastic surgery residents yielded a reduction in the "Hispanic/ Latino" group (4% -3%, P = 0.01). Faculty data showed an increase in "Hispanic/ Latino" (4% -5%, P < 0.01) and "other" (4% -5%, P = 0.02) groups with a reduction in "White" faculty members (74% -70%, P < 0.01). Final recommendations for diversity recruitment were then formed from diversity and inclusion officer interviews. CONCLUSIONS: Continuous and sustainable work with respect to diversity and inclusion within plastic surgery has an opportunity for growth. Implementation of key recommendations by residency programs can change the face of our specialty going forward.

Sensitization and Desensitization in Vascularized Composite Allotransplantation.

Vascularized composite allotransplantation (VCA) is a field under research and has emerged as an alternative option for the repair of severe disfiguring defects that result from severe tissue loss in a selected group of patients. Lifelong immunosuppressive therapy, immunosuppression associated complications, and the effects of the host immune response in the graft are major concerns in this type of quality-of-life transplant. The initial management of extensive soft tissue injury can lead to the development of anti-HLA antibodies through injury-related factors, transfusion and cadaveric grafting. The role of antibody-mediated rejection, donor-specific antibody (DSA) formation and graft rejection in the context of VCA still remain poorly understood. The most common antigenic target of preexisting alloantibodies are MHC mismatches, though recognition of ABO incompatible antigens, minor histocompatibility complexes and endothelial cells has also been shown to contribute to rejection. Mechanistically, alloantibody-mediated tissue damage occurs primarily through complement fixation as well as through antibody-dependent cellular toxicity. If DSA exist, activation of complement and coagulation cascades can result in vascular thrombosis and infarction and thus rejection and graft loss. Both preexisting DSA but especially de-novo DSA are currently considered as main contributors to late allograft injury and graft failure. Desensitization protocols are currently being developed for VCA, mainly including removal of alloantibodies whereas treatment of established antibody-mediated rejection is achieved through high dose intravenous immunoglobulins. The long-term efficacy of such therapies in sensitized VCA recipients is currently unknown. The current evidence base for sensitizing events and outcomes in reconstructive transplantation is limited. However, current data show that VCA transplantation has been performed in the setting of HLA-sensitization.

Psychosocial considerations in the assessment of hand transplant candidates: A single-center experience and brief literature review.

Vascularized composite allograft, including hand transplantation (HT), has gained wider usage as a reconstructive treatment over the past 30 years. HT recipients face unique psychosocial challenges compared to their solid organ and/or bone marrow transplant counterparts. Accordingly, the psychosocial evaluation among HT candidates continues to evolve, leaving a lack of consensus as to the critical psychosocial domains and psychometric testing instruments to help evaluate individuals considering HT. The present manuscript describes the psychosocial evaluation process within the Duke HT program, which been contacted by 80 potential candidates since 2014. The Duke HT evaluation process incorporates a comprehensive psychosocial assessment within domains including personality, cognitive function, mood, behavioral adherence, social support, and substance use history, among others. Our experience underscores the potential utility of collecting thorough psychosocial evaluations, supplemented by psychometric test data, to comprehensively assess potential HT candidates.

Vascularized composite allotransplants as a mechanistic model for allograft rejection - an experimental study.

Vascularized composite allotransplants (VCAs) seem to have several unique features of clinical and experimental importance, including uniquely definable lymphatic drainage that can be easily accessed at the level of ipsilateral regional node beds. Thus, VCA offers a unique opportunity to assess the relative contribution of peripheral and secondary lymphoid tissue to the process of rejection. We transplanted hind limb grafts from C3H donors to six different groups of C57BL/6 recipients: Spleen+ Map3k14-/- ; Spleen- Map3k14-/- ; Spleen+ Node- Map3k14-/- ; and Spleen- Node- Map3k14-/- . As positive controls, we used Map3k14+/- with or without spleen. Map3k14+/- mice demonstrated an average graft survival of 9.6 and 9.2 days for Spleen- and Spleen+ Map3k14+/- , respectively. Rejection in the Map3k14-/- group was considerably delayed (28.4 days, P = 0.002) in all recipients. The Spleen- Map3k14-/- mice rejected their hind limb allografts in an even more delayed fashion compared to Spleen+ Map3k14-/- (54.4 days, P = 0.02). Histological analysis of skin showed that acute rejection in both Map3k14+/- mice groups was graded as Banff III or Banff IV. In the Map3k14-/- groups, rejection was graded as Banff III. We demonstrated that in the absence of lymph nodes, grafts reject in a delayed fashion. Also, splenectomy in alymphoplastic mice further extends graft survival, but does not eliminate rejection all together.

The Legacy of Joseph A. Moylan, M.D.: "It's About Everyone Else".

The history of modern American surgery is marked by larger-than-life pioneers who have made transformative contributions to our field. These extraordinary individuals have been known primarily for their technical and clinical mastery, development of novel surgical procedures and techniques, extraordinary abilities in the education and training of surgeons, and/or innovative discoveries in biomedical science. While mastery in clinical surgery, education, and research have come to characterize the consummate academic surgeon, challenging social inequities of today now demand deeper engagement in another vital arena. This historical account is the story of a truly exceptional surgeon and visionary who spent much of his life leading that very charge. Early in his career, Dr. Joseph Moylan recognized and embraced this obligation to go beyond the walls of the hospital and out into the community to combat social factors leading to adverse outcomes for at-risk young men. His legacy itself represents a vehicle for empowering youth confronted with barriers to educational opportunities and experiences. Furthermore, recounting Joe's journey conveys the over-arching thesis that surgeons have the opportunity-and, indeed, are well positioned-to engage more deeply with their communities, to lead efforts to address social determinants at their roots and to create a pipeline of bright young scholars and potential future surgeons.

Vascularized composite allotransplantation in the United States: A retrospective analysis of the Organ Procurement and Transplantation Network data after 5 years of the Final Rule.

On July 3, 2014, the Organ Procurement and Transplantation Network (OPTN) began overseeing vascularized composite allotransplantation/allografts (VCA) in the United States. For the past 6 years, centers performing VCAs have been requested to submit data into a biometric repository, in parallel with systems used by solid organ transplant centers. Currently, 62 VCAs are reported in the entire OPTN database, with 36 of these transplants reported as performed after VCA was added to the OPTN Final Rule. Of these 36 recipients, 16 received uterus transplants, most of which (11) occurred from living donors. Ten patients received hand transplants and 6 received face transplants. Two patients received abdominal wall transplants, 1 patient received a scalp transplant, and 1 patient received a penile transplant. The present manuscript represents the query of a nationalized database for VCA type, immunosuppression treatment, and clinical outcomes for VCAs. This manuscript provides a report of the current VCA data reported to the OPTN after the Final Rule.

Costimulation Blockade in Vascularized Composite Allotransplantation.

Vascular composite allotransplantation (VCA) is a field under research and has emerged as an alternative option for the repair of severe disfiguring defects that result from infections or traumatic amputation in a selected group of patients. VCA is performed in centers with appropriate expertise, experience and adequate resources to effectively manage the complexity and complications of this treatment. Lifelong immunosuppressive therapy, immunosuppression associated complications, and the effects of the host immune response in the graft are major concerns in VCA. VCA is considered a quality of life transplant and the risk-benefit ratio is dissimilar to life saving transplants. Belatacept seems a promising drug that prolongs patient and graft survival in kidney transplantation and it could also be an alternative approach to VCA immunosuppression. In this review, we are summarizing current literature about the role of costimulation blockade, with a focus on belatacept in VCA.

Introducing a novel experimental model of bladder transplantation in mice.

Bladder dysfunction is a common clinical problem attributed to various conditions such as posterior urethral valves, neurogenic bladder, ureteral ectopy, or bladder exstrophy. Currently, the main therapeutic option for these dysfunctions is neobladder reconstruction with gastrointestinal tract segments. However, the latter was associated with significant long-term complications. To provide a new candidate of possible surgical solution for bladder dysfunction, we propose a novel orthotropic mouse bladder transplantation model. The donor bladder with abdominal aorta and inferior vena cava was isolated and orthotopically sutured to the recipient, whose bladder above the ureteral opening level was removed. The recipient mice showed more than 80% 6-month survival rate and comparable body weight to control mice. At both 1 month and 6 months posttransplant, the urine voiding behavior of recipient mice and control mice was monitored by cystometry. We found that the recipient mice displayed similar bladder pressure and urine secretion ability compared to control mice especially at 6 months posttransplant. Similarity of bladder structure between recipient and control mice was confirmed by histology. As a proof of principle, we tested our model in an allogeneic setting. Early acute rejection was noted after day 5 that was histologically more profound by day 10 posttransplant. These results indicate that the mouse bladder transplant is able to provide normal bladder function.

Th17 cell inhibition in a costimulation blockade-based regimen for vascularized composite allotransplantation using a nonhuman primate model.

Vascularized composite allotransplantation (VCA) is challenged by the morbidity of immunosuppression required to prevent rejection. The use of highly specific biologics has not been well explored in VCA. Given that psoriasis is T-cell mediated, as is rejection of skin-containing VCAs, we sought to assess the role of ustekinumab and secukinumab, which are approved to treat psoriasis by inhibiting Th17 cells. We combined these agents with belatacept and steroids in a VCA nonhuman primate model. Group I consisted of belatacept and steroids, group II was belatacept, ustekinumab with steroid taper, and group III was belatacept, secukinumab with steroid taper. Three animals were transplanted in each group. In group I, the mean graft survival time until the first sign of rejection was 10 days whereas in group II and III it was 10.33 and 11 days, respectively. The immunohistochemistry analysis showed that the number of IL-17a+ cells and the intensity of IL-17a expression were significantly reduced in both dermis and hypodermis parts in groups II and III when compared to group I (P < 0.01). Ustekinumab and secukinumab led to less T-cell infiltration and IL-17a expression in the allograft but provided no benefit to belatacept and steroids in VCA survival.

Hand transplantation in the United States: A review of the Organ Procurement and Transplantation Network/United Network for Organ Sharing Database.

Hand transplantation is the most common application of vascularized composite allotransplantation (VCA). Since July 3, 2014, VCAs were added to the definition of organs covered by federal regulation (the Organ Procurement and Transplantation Network (OPTN) Final Rule) and legislation (the National Organ Transplant Act). As such, VCA is subject to requirements including data submission. We performed an analysis of recipients reported to the OPTN to have received hand transplantation between 1999 and 2018. Forty-three patients were identified as having been listed for upper extremity transplantation in the United States. Of these, 22 received transplantation prior to July 3, 2014 and 10 from then to December 31, 2018. Of patients transplanted after 2014, posttransplant functional scores included a decrease in Disabilities of the Arm, Shoulder and Hand questionnaire in 3 of 10 patients, Carroll test scores ranging from 9 to 60 of 99, and monofilament testing with protective sensation achieved in 4 of 6 patients. Complications included rejection in nine recipients with Banff scores from II-IV. One patient experienced graft failure 5 days after transplantation. Of the remaining patients, two were reported as receiving monotherapy and seven receiving dual or triple immunosuppression therapy. The inclusion of VCA in the OPTN Final Rule standardized parameters for safe implementation and data collection.

Psychosocial dimensions of hand transplantation: lessons learned from solid organ transplantation.

PURPOSE OF REVIEW: The present review examines psychosocial factors emerging as predictive of clinical outcomes among solid organ transplant (SOT) recipients, with possible extensions to vascular composite allograft (VCA) and hand transplantation, in particular. The Chauvet Workgroup report and International Society of Heart and Lung Transplantation consensus guidelines are used to delineate areas of commonality between SOT and VCA, as well as unique features contributing to post-VCA psychosocial risk. RECENT FINDINGS: Increasing evidence suggests that depression, cognitive function, and other posttransplant psychosocial factors consistently associate with clinical risk in SOT. However, the mechanisms precipitating these psychosocial risk factors are likely diverse in their cause, with large individual differences across SOT and VCA. Transdiagnostic dimensions may serve as mechanistic factors, increasing the risk of adverse clinical outcomes and suggesting potential treatment strategies for risk mitigation. Psychosocial dimensions including psychological flexibility, self-efficacy, and posttraumatic growth are discussed as potential contributory factors. SUMMARY: Psychosocial factors hold importance in predicting posttransplant clinical outcomes. Emerging transdiagnostic factors may provide insight into mechanisms and potential treatments.

Neural activation for actual and imagined movement following unilateral hand transplantation: a case study.

Transplantation of a donor hand has been successful as a surgical treatment following amputation, but little is known regarding the brain mechanisms contributing to the recovery of motor function. We report functional magnetic resonance imaging (fMRI) findings for neural activation related to actual and imagined movement, for a 54-year-old male patient, who had received a donor hand transplant 50 years following amputation. Two assessments, conducted 3 months and 6 months post-operatively, demonstrate engagement of motor-control related brain regions for the transplanted hand, during both actual and imagined movement of the fingers. The intact hand exhibited a more intense and focused pattern of activation for actual movement relative to imagined movement, whereas activation for the transplanted hand was more widely distributed and did not clearly differentiate actual and imagined movement. However, the spatial overlap of actual-movement and imagined-movement voxels, for the transplanted hand, did increase over time to a level comparable to that of the intact hand. At these relatively early post-operative assessments, brain regions outside of the canonical motor-control networks appear to be supporting movement of the transplanted hand.

Small bowel and abdominal wall transplantation: A novel technique for synchronous revascularization.

Abdominal wall transplantation (AWT) was introduced in 1999 in the context of reconstruction of complex abdominal wall defects in conjunction with visceral organ transplantation. As of recently, 38 cases of total AWT have been performed worldwide, about half of which were performed in the United States. While AWT is technically feasible, one of the major challenges presenting to the reconstructive surgeon is time to revascularization of the donor abdominal wall (AW), given the immediate proximity of the visceral organ and AWT. The authors report a novel AW revascularization technique during a synchronous small bowel and AWT in a 37-year-old man.

Vascularized composite allotransplantation in the United States: A descriptive analysis of the Organ Procurement and Transplantation Network Data.

On July 3, 2014, the Organ Procurement and Transplantation Network/United Network for Organ Sharing was charged with the oversight of vascularized composite allograft (VCA) procurement and transplantation in the United States. As of December 31, 2017, 61 VCA programs at 27 centers were approved in the United States. Fifty candidates have been added to the waiting list at 15 centers. Twenty-eight VCA transplants have been performed at 14 programs (10 upper limb, 10 uterus, 5 craniofacial, 1 scalp, 1 abdominal wall, and 1 penile). Twenty-two VCAs were procured from 21 deceased donors, resulting in 109 non-VCA organs transplanted (15 hearts, 3 intestine, 40 kidney, 20 livers, 24 lungs, and 7 pancreata). Six uterus transplants were performed from living donors. Fourteen candidates were still waiting at 9 centers on December 31, 2017. Two of the 10 uterus recipients had live births and 3 still had viable grafts. Seventeen of 18 nonuterus recipients had functioning grafts. At present, VCA is an emerging field with a small number of patients transplanted. Data on posttransplant survival and functional outcomes continue to be collected to further the understanding of this complex and evolving field. Further systematic data are important for policy refinement and assurance of patient safety.

De novo belatacept in clinical vascularized composite allotransplantation.

Most immunosuppressive regimens used in clinical vascularized composite allotransplantation (VCA) have been calcineurin inhibitor (CNI)-based. As such, most recipients have experienced CNI-related side effects. Costimulation blockade, specifically CD28/B7 inhibition with belatacept, has emerged as a clinical replacement for CNI-based immunosuppression in kidney transplantation. We have previously shown that belatacept can be used as a centerpiece immunosuppressant for VCA in nonhuman primates, and subsequently reported successful conversion from a CNI-based regimen to a belatacept-based regimen after clinical hand transplantation. We now report on the case of a hand transplant recipient, whom we have successfully treated with a de novo belatacept-based regimen, transitioned to a CNI-free regimen. This case demonstrates that belatacept can provide sufficient prophylaxis from rejection without chronic CNI-associated side effects, a particularly important goal in nonlifesaving solid organ transplants such as VCA.

Vascularized composite allotransplantation: a closer look at the banff working classification.

The first Banff vascularized composite allotransplantation meeting was held in 2007 to standardize criteria for the characterization and reporting of severity and types of rejection. As a result, the 2007 Banff VCA working classification for skin allograft pathology was formalized and now serves as the standard for diagnosis of VCA rejection. Similar to other working classification systems, strengths and limitations have been identified including the adequacy of the specimen, the definition of severity between grades, the reproducibility, the adequacy of the specimens, the types of rejection, and the integration of newer technologies such as molecular and genomic approaches. Although a relatively few number of cases have been performed and followed up to date, additional phenotypes such as antibody-mediated rejection, fibrosis, atrophy, and vascular changes are being reported and characterized based on accumulated experience in the field of VCA and parallels with other solid organs. This study aims to consider strengths and limitations of the Banff VCA working system and highlights ongoing challenges and opportunities available related to histopathology in this emerging field of transplantation.