Vascularized Composite Allografts Research Articles

Public Perceptions of Cross-Sex Vascularized Composite Allotransplantation

Cross-sex vascularized composite allotransplantation has been performed in cadaveric facial transplantation and clinical extremity transplantation. Understanding the challenge of appropriate donor-recipient matching, this study sought to characterize the public's perception of cross-sex vascularized composite allotransplantation. Participants were surveyed in New York City. Data collected included demographics and willingness to donate vascularized composite allografts (VCAs) of various types. Similar questions were asked in the context of same-sex and cross-sex donation. A total of 101 participants (male: 56.4%; age ≤35 years: 62.4%) were surveyed. The majority expressed willingness to donate to recipients of a different sex (hand: 78.2%, face: 56.4%, penis or uterus: 69.3%, lower limb: 81.2%, abdominal wall: 80.2%, larynx: 81.2%, and solid organs: 85.2%). Among VCAs, willingness to donate facial allografts was significantly different in same-sex versus cross-sex contexts (64.4% vs 56.4%; P = 0.008). Participants were also significantly more likely to donate VCAs to same-sex recipients on behalf of themselves versus loved ones (P < 0.05). There was significantly lower willingness to receive cross-sex versus same-sex facial (P = 0.022) and genital allografts (P = 0.022). Education on the preservation of recipient masculinity or femininity in cross-sex facial transplantation increased participants' willingness to receive a cross-sex face transplant from 56.4% to 71.3% (P = 0.001). This study highlights the urban public's acceptance of VCA donation or reception regardless of sex mismatch. There is increased willingness to receive a cross-sex face transplant after education, highlighting opportunities for future focused interventions to increase public awareness and ultimately the donor pool.

Tolerance Protocols in Large Animal VCA Models—Comprehensive Review

The clinical application of vascularized composite allografts (VCA) has continue to expand each year as new transplants are performed. However, chronic rejection and the many side effects from chronic immunosuppression continue to inhibit widespread application of VCA. Immune tolerance to VCA would address these two issues and shift the risk-benefit ratio to allow for the more widespread application of these transplants. Future development of clinical tolerance protocols will be generated from pre-clinical experiments performed in large animal models. This article reviews the current state of large animal tolerance protocols published for VCA. The most successful tolerance protocols thus far include the use of hematopoietic stem cell transplant with non-myeloablative preconditioning and establishment of donor cell chimerism. In addition to this strategy, several groups have examined the inclusion of mesenchymal and adipose-derived stem cells to address the complications related to the use of hematopoietic stem cell transplant (such as graft versus host disease). These large animal models are critical to development of a viable pre-clinical model for tolerance in vascularized composite allografts that can deliver a tolerant state with minimal harm to the recipient of these non-life-saving transplants.

Vascular composite allograft at a crossroads

This month's installment of “The AJT Report” looks at vascular composite allograft and the challenges of expanding the use of this rarely performed but potentially life-changing reconstructive procedure. We report on how wearable healthcare devices might one day play a valuable role in the transplant field.

Current and future regulatory and financial challenges in vascularized composite allotransplantation.

To discuss current and future regulatory and financial issues affecting the field of vascularized composite allotransplantation (VCA). Vascularized composite allografts are regulated by the US Department of Health and Human Services Organ Procurement and Transplantation Network Final Rule (42 CFR part 121) in the United States and Directive 2010/53/EU of the European Parliament and the Council of 7 July 2010 in the European Union (EU). However, in the United States and most of the EU, VCA is not yet paid for by insurance or third-party payers and many centers depend upon grant funding, philanthropic gifts, and/or supplemental hospital/institutional funding strategies to pay for the transplants and postoperative care. In the absence of randomized clinical trial data, which is infeasible for studying VCA outcomes, consensus data sets are needed to document these procedures' value proposition and have them accepted as part of the standard of care. Procedure and immunosuppression protocol variability applied to a small patient cohort necessitates collaborative efforts by field experts to devise creative approaches, such as determining return-on-investment for anatomical subunits, to better understand these transplants' value and impact on patient quality-of-life.

Maximizing donors' gifts: A comparison of actual and expected solid organ yield among VCA donors.

Vascularized Composite Allograft (VCA) transplantation provides life-changing transplants, but VCA adds complexity to the donation process and timing, possibly impeding solid organ donation. Expanding upon descriptive analyses, this study examines risk-adjusted predictions versus the observed number of organs donated by VCA donors. Our cohort included VCA donors in the United States during January 1, 2008-December 31, 2017 (n=51), using OPTN Deceased Donor Registration Form data and the Scientific Registry of Transplant Recipients (SRTR) donor yield models to calculate observed-to-expected (O:E) yield ratios. Almost all VCA donors' livers (48/51; 94.1%) and kidneys (92/102; 90.2%) were transplanted, with fewer hearts (28/51; 54.9%), lungs (46/102; 45.1%), pancreata (15/51; 29.4%), and intestines (3/51; 5.9%) transplanted. O:E ratios for overall organ yield were slightly greater than expected for VCA donors (1.10; 95% CI: 1.02-1.17). Liver (1.17: 1.08-1.27) and lung yields (1.38: 1.07-1.68) were both greater than expected, while kidney, heart, and pancreas yields were similar to expected. Across VCA types, bilateral upper limb and abdominal wall donors had better-than-expected yields while uterus, face, and unilateral upper limb donors all had similar-to-expected yields. Solid organ yield among VCA donors was as good or better than predicted, suggesting that VCA donation does not compromise recovery and transplantation of lifesaving organs.

Evaluating the Effects of Brain Death Physiology and Immunosuppression on the Muscle-derived Stem Cell Niche in a Large Animal Transplant Model

BACKGROUND: Muscle-derived stem cells (MDSCs) have been shown to be robust mediators of tissue regeneration and mixed chimerism in small animal murine transplant models. The effects of transplant and brain death (BD) physiology on MDSCs are understudied in large animal translational models. Our study aim was to evaluate the viability, quantity, and stem cell differentiation of MDSCs under various conditions in a porcine vascularized composite allografts (VCA) model. We hypothesized that BD negatively affect the MDSC stem cell-niche in VCA. METHODS: MDSCs were harvested from the hind-limbs of pigs under the following conditions: (1) pre-BD donor, (2) post-BD donor, (3) immunosuppressed transplanted donor VCA, and (4) immunosuppressed recipient muscle (contralateral leg). Stem cell markers were evaluated in all groups using flow cytometry with standard stem markers (CFS, APC, PERCP) and stem cell presence further confirmed in the pre-BD group with differentiation assays. Samples were harvested at the time of transplant and 7 days after transplantation. MDSC populations were isolated using a modified collagen-sorting preplate technique. Fluorescent and bright field microscopy was used at various time points (0–10 days) to evaluate cell expansion and growth. Images were analyzed for confluence and differentiation stains using ImageJ, and statistical analysis was performed using Mathematica. RESULTS: Flow-cytometry demonstrated significantly higher population of stem cell markers PERCP (27% versus 7%), CFS (43% versus 14%), and APC (61% versus 12%) in pre-BD versus post-BD groups (P = 0.001). Differentiation assays confirmed stem cell presence in the pre-BD differentiation assays, with significantly increased differentiation with later pre-plates for osteogenesis, chrondrogenesis, and adipogenesis (P < 0.01).Percent confluence at 10 days was greatest in the pre-BD and lowest in post-BD conditions (81% versus 39%; P < 0.01). The immunosuppressed transplant donor VCA showed greater percent confluence compared to the immunosuppressed recipient muscle (71% versus 55%; P < 0.01), although this remained at a lower level than the pre-BD condition (71% versus 81%; P < 0.01). CONCLUSION: BD and immunosuppression each impair MDSC niche expansion and mitosis based on time to confluence. However, our study demonstrates that successful transplantation partially reverses the negative effects of BD. Future investigations will focus on further ameliorating BD effects to optimize the MDSC stem cell niche prior to transplant.

Vascularized composite allotransplantation: Knowledge and attitudes of a national sample of organ procurement organization professionals.

With the emergence of vascularized composite allografts (VCAs) for transplantation, donation professionals' ability to obtain authorization for these anatomical gifts has become paramount for its continued practice. Our national study examines the experience of organ procurement organization (OPO) professionals responsible for presenting the opportunity to donate VCAs to families of deceased donor-eligible patients. Semi-structured telephone interviews conducted with 157 OPO staff assessed experience with VCA discussions, VCA knowledge, and comfort, confidence, and feeling prepared with discussions about different VCA types. Standard procedures were used to code and analyze the qualitative data and summarize the quantitative data. Most respondents (70.1%) never held a VCA donation discussion, but those with experience reported overall low levels of knowledge, comfort, and confidence talking with families about VCA. Although 44.4% of the sample had VCA-related training, many felt unprepared, with most (75.0%) stating the training was insufficient. Participants without experience indicated even lower ratings of the aforementioned constructs. Findings support extant work demonstrating that no standardized procedures exist for VCA donation discussions; however, donation professionals are willing to adopt new VCA-related skills. This report concludes that sustained and content-specific training will elevate donation professionals' ability to augment the supply of VCAs available for transplantation.

Developing an International Registry for Uterus Transplantation (IRUTx): Promises and Challenges.

Uterus Transplantation (UTx) is an experimental vascular composite allograft designed to provide women with absolute uterine factor infertility with the opportunity to gestate and give birth to their future offspring. The number of UTx procedures performed worldwide now stands at ≥70 and as the number of cases performed increases so too does the volume of potential data that may be gathered to inform the development, practice and regulation of UTx. Given the value of this data, and the challenges associated with keeping track of cases and outcomes where data remains unpublished and/or scattered, scientists and academics conducting research into UTx have increasingly called for the swift creation, implementation and management of an international registry for Uterus Transplantation (IRUTx). This article explores and provides practical guidance regarding the potential benefits the IRUTx may provide to stakeholders, as well as the legal and ethical challenges that its creation may pose in terms of dataset design, consent, privacy, researcher compliance and governance.

Cutaneous leukocyte lineages in tolerant large animal and immunosuppressed clinical vascularized composite allograft recipients.

Vascularized composite allografts (VCAs) can restore fully functional anatomic units in patients with limb amputations or severe facial tissue loss. However, acute rejection of the skin is frequently observed and underscores the importance of developing tolerance induction protocols. In this study, we have characterized the skin immune system in VCAs. We demonstrate infiltration of recipient leukocytes, regardless of rejection status, and in tolerant mixed hematopoietic chimeras, the co-existence of these cells with donor leukocytes in the absence of rejection. Here we characterize the dermal T cell and epidermal Langerhans cell components of the skin immune system in our porcine model of VCA tolerance, and the kinetics of cutaneous chimerism in both of these populations in VCAs transplanted to tolerant and nontolerant recipients, as well as in host skin. Furthermore, in biopsies from the first patient to receive a hand transplant in our program, we demonstrate the presence of recipient T cells in the skin of the transplanted limb in the absence of clinical or histological evidence of rejection.

Partial Loss of Nasal Tissue in a Facial Vascularized Composite Allograft Patient.

Supplemental Digital Content is available in the text.

Infectious complications of vascularized composite allograft transplantation.

Vascularized composite allograft (VCA) transplants constitute multiple tissues transplanted together as one functional unit. These procedures are increasing in frequency and complexity, yet data about graft survival, quality of life, and infection risk remain limited. Informative guidance for this patient population is often inferred from the solid organ transplantation literature. Yet, it is important to understand that VCA transplantation additionally carries its own significant and distinctive risk factors for infection. In this review, we give an overview of previously described infectious complications of VCA transplantation in the literature, discuss risk factors for future infection in these patients, and discuss how to manage such obstacles.

Structure and Function of Porcine Arteries Are Preserved for up to 6 Days Using the HypoRP Cold-storage Solution.

Maintaining functional vessels during preservation of vascularized composite allografts (VCAs) remains a major challenge. The University of Wisconsin (UW) solution has demonstrated significant short-term benefits (4-6 h). Here we determined whether the new hypothermic resuscitation and preservation solution HypoRP improves both structure, survival, and function of pig arteries during storage for up to 6 days. Using porcine swine mesenteric arteries, the effects of up to 6-day incubation in a saline (PBS), UW, or HypoRP solution on the structure, cell viability, metabolism, and function were determined. After incubation at 4°C, for up to 6 days, the structures of the arteries were significantly disrupted, especially the tunica media, following incubation in PBS, in contrast with incubation in the HypoRP solution and to a lesser extent, in UW solution. Those disruptions were associated with increased active caspase 3 indicative of apoptosis. Additionally, while incubation in PBS led to a significant decrease in the metabolic activity, UW and HypoRP solutions allowed a stable to increased metabolic activity following 6 days of cold storage. Functional responsiveness to phenylephrine (PE) and sodium nitroprusside (SNP) decreased over time for artery rings stored in PBS and UW solution but not for those stored in HypoRP solution. Moreover, artery rings cold-stored in HypoRP solution were more sensitive to ATP. The HypoRP solution improved long-term cold storage of porcine arteries by limiting structural alterations, including the collagen matrix, reducing apoptosis, and maintaining artery contraction-relaxation functions for up to 6 days.

Local Immunosuppression for Vascularized Composite Allografts: Application of Topical FK506-TyroSpheres in a Nonhuman Primate Model.

Transplantation of vascularized composite allografts (VCAs) provides a means of restoring complex anatomical and functional units following burns and other disfigurement otherwise not amenable to conventional autologous reconstructive surgery. While short- to intermediate-term VCA survival is largely dependent on patient compliance with medication, the myriad of side effects resulting from lifelong systemic immunosuppression continue to pose a significant challenge. Topical immunosuppression is therefore a logical and attractive alternative for VCA. Current formulations are limited though, by poor skin penetration but this may be mitigated by conjugation of immunosuppressive drugs to TyroSpheres for enhanced delivery. Therefore, we investigated the topical application of FK506-TyroSpheres (in the form of a gel dressing) in a clinically relevant nonhuman primate VCA model to determine if allograft survival could be prolonged at reduced levels of maintenance systemic immunosuppression. Six Major Histocompatibility Complex (MHC)-mismatched cynomolgus macaques (Macaca fascicularis) served as reciprocal donors and recipients of radial forearm fasciocutaneous flaps. Standard Bacitracin ointment and FK506-TyroSpheres were applied every other day to the VCAs of animals in groups 1 (controls, n = 2) and 2 (experimental, n = 4), respectively, before gradual taper of systemic FK506. Clinical features of VCA rejection still developed when systemic FK506 fell below 10 ng/ml despite application of FK506-TyroSpheres and prolonged VCA survival was not achieved. However, unwanted systemic FK506 absorption was avoided with TyroSphere technology. Further refinement to optimize local drug delivery profiles to achieve and maintain therapeutic delivery of FK506 with TyroSpheres is underway, leveraging significant experience in controlled drug delivery to mitigate acute rejection of VCAs.

Abstract 95: S-nitrosylation Therapy To Improve Ex-vivo Parameters Of Vascular Composite (vca): Study On Brain Dead Porcine

S-Nitrosylation Improves ex-vivo parameters of vascular composite (VCA): Study on brain dead swine Background: Brain death (BD) results in disruption of S-Nitrosohemoglobin (SNO-Hb) leading to decrease tissue micro perfusion. In a pre-clinical study on bd swine, we found that repletion of SNO-Hb by S-nitrosylation agent as ethyl nitrite (ENO) improves organ function. Vascularized composite allograft (VCA) is a viable therapeutic option for correction of composite tissue loss as limb amputation, abdominal trauma and severe facial damage. Although significant progress has been made with VCA surgical techniques and anti-rejection drug regimens, less attention has been directed to care of the tissue composite preservation. It is the physiologic status of the donor that often drives tissue availability and short-term VCA outcome. We hypothesized that additional of ENO during composite storage could restore composite microcirculation and thus improves outcome. Methods: VCA (n=8) and hind limb (n=6) were harvested from induced bd swine. Each composite was placed on a Lifeport storage machine and cold pulsatile perfusion was started at a targeted pressure 22 ± 5 mmHg for VCA and 13±2 for limb. Flow and resistance measurements were recorded during the experiment. ENO was aerated to the preservative solution for 2 hours (50ppm) for the treated composites. Data points were extracted from machine-generated values. Rate of change (slope) in flow rate and resistance were calculated. We compared values from control group to ENO treated group using Wilcoxon rank sum tests. GraphPad Prism software was used and considered a p < 0.05 to be statistically significant. Results: Flow and resistance measurements were expressed as percent change from baseline. For the duration of the pumping period. VCA flow rate in the ENO-treated group (n=2) was significantly higher (p<0.0001; 95% CI -17.22 to -9.743) than the control group (n=6), As well as, resistance was significantly decreased in ENO-treated group (p=0.0004; 95% CI 11.86 to 33.96). Similarly, limbs flow rate in the ENO-treated group (n=3) was significantly higher (p<0.0001; 95% CI -11.52 to -2.36) than control limb (n=3) as well as resistance significantly decreased in ENO-treated group (p<0.0001; 95% CI 11.51 to 24.13). Conclusions: S-nitrosylation therapy (ENO) during ex vivo storage of VCA holds promise to increase the number and quality of VCA available for transplant.

Abstract 43: Evaluation The Effect Of Brain-death Physiology And Immunosuppression On Muscle-derived Stem Cell Expansion: Study On Porcine Tissue

Background: Muscle-derived stem cells (MDSCs) are robust mediators of tissue regeneration that have been shown, in the literature, to exhibit multipotency in murine models. We hypothesize that immunosuppression, transplant physiology, and braindeath negatively affect the stem cell-niche in vascularized composite allografts (VCA) and may affect tolerance/rejection. Our study aim was to evaluate the growth of MDSCs under these conditions in a porcine VCA model. Methods: Muscle samples were harvested from the hind-limbs of pig before and after inducing brain-death. Samples were then harvested from both the VCA of another immunosuppressed pig and from the contralateral hindlimb of the same recipient 7 days after transplantation. MDSC populations were isolated using a modified collagen-sorting preplate technique. Imaging was obtained at various time points (t=0-10 days). Images were analyzed for confluence using ImageJ, statistical analysis was performed using Mathematica. Results: Time to confluence (t = 3, 5, 7, 10 days) between pre-braindeath and post-braindeath MDSC populations was significantly different (20%, 38%, 75%, 81% vs. 7%, 17%, 31%, 39%) (p<0.01). Time to confluence (t = 2, 4, 6, 8, 10 days) between immunosuppressed recipient and allograft MDSC populations was significantly different (3%, 6%, 13%, 45%, 55% vs. 7% 11%, 39%, 53%, 71%, respectively) (p=0.02). At t=10 days, mean confluence between pre-BD and immunosuppressed recipient MDSC populations was significantly different (81% vs. 55%) (p < 0.01); similarly, mean confluence between pre-braindeath and allograft MDSC populations was also significantly different (81% vs. 71%) (p = 0.01). At t=10 days, mean confluence between post-braindeath and immunosuppressed recipient MDSC populations was significantly different (39% vs. 55%) (p<0.01). Conclusion: Brain-death and immunosuppression significantly impair MDSC expansion and mitosis based on time to confluence; however, transplantation may ameliorate the negative effects of immunosuppression by acting as a surrogate for trauma and inflammation. Brain-death physiology appears to have the greatest impact on MDSC expansion in our study. Further studies will focus on immune modulation and scaffold growth in porcine MDSC populations.

Is Vascularized Composite Allograft Transplantation Experimental or an Accepted Surgical Procedure: Results from a National Survey.

More than 85 patients have received over 100 hand/arm transplants and more than 35 patients have received full or partial face transplants at institutions around the world. Given over two decades of experience in the field and in the light of successful outcomes with up to 17 years follow up time, should we still consider vascularized composite allograft (VCA) as a research/clinical investigation? We present the results of a nationwide electronic survey whose intent was to gather institutional bias with regard to this question. An 11 question survey that was developed by VCA advisory committee of American Society of Transplantation was sent to all identified Internal Review Board chairs or directors in the United States. We received a total of 54 responses (25.3%) to the survey. The majority (78%) of responses came from either the chairperson, director, or someone who is administratively responsible for an IRB. Though certainly not an exhaustive investigation into each institution's preference, we present a representative sampling. The results of which favor VCA as an accepted clinical procedure given the appropriate setting. Further research is needed to fully ascertain practices at each individual institution.

Imaging the distribution of iron oxide nanoparticles in hypothermic perfused tissues.

Herein, we evaluate the use of MRI as a tool for assessing iron oxide nanoparticle (IONP) distribution within IONP perfused organs and vascularized composite allografts (VCAs) (i.e., hindlimbs) prepared for cryopreservation. Magnetic resonance imaging was performed on room-temperature organs and VCAs perfused with IONPs and were assessed at 9.4 T. Quantitative T1 mapping and -weighted images were acquired using sweep imaging with Fourier transformation and gradient-echo sequences, respectively. Verification of IONP localization was performed through histological assessment and microcomputer tomography. Quantitative imaging was achieved for organs and VCAs perfused with up to 642 mMFe (36 mgFe /mL), which is above previous demonstrations of upper limit detection in agarose (35.7mMFe [2 mgFe /mL]). The stability of IONPs in the perfusate had an effect on the quality of distribution and imaging within organs or VCA. Finally, MRI provided more accurate IONP localization than Prussian blue histological staining in this system, wherein IONPs remain primarily in the vasculature. Using MRI, we were able to assess the distribution of IONPs throughout organs and VCAs varying in complexity. Additional studies are necessary to better understand this system and validate the calibration between T1 measurements and IONP concentration.

Editorial introductions

Current Opinion in Organ Transplantation was launched in 1996. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of organ transplantation is divided into 18 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Xian C. LiXian C. LiDr Xian C. Li is Professor of Immunology, Weill Cornell Medicine of Cornell University and director of Immunobiology &Transplant Sciences at Houston Methodist Hospital in Houston Texas. He also holds the Max and Lillie Frosch Centennial Chair at Houston Methodist. His lab studies the fundamental mechanisms of transplant rejection and transplant tolerance. The goal of his team is to advance transplant medicine through fundamental research. Dr. Xian Li is recognized with many awards and elected memberships; He received the American Society of Transplantation (AST) Young Investigator Award, AST Wyeth Basic Science Award, and the AST Wyeth Achievement Award. Dr. Li has served in the AST basic science advisory council, TTS basic science committee, chair of the AST Grants Executive Committee, and Chair of ATC 2018. He is an elected member of the American Society for Clinical Investigation, a standing member of the NIH study sections and DOD grant review panels. He is now an associate editor of American Journal of Transplantation and the journal of Transplantation. Linda C. CendalesLinda C. CendalesDr Linda C. Cendales, MD, is an Associate Professor of Surgery, a Duke Health Scholar, and the Director of the Vascularized Composite Allotransplantation at Duke University Medical Center. During her fellowship in Hand and Microsurgery, Dr Cendales helped organize the first VCA team in the U.S. and participated in the country's first two hand transplants in Louisville, KY. She was subsequently the first surgeon accepted into the Transplant Surgery and Immunobiology Fellowship at the National Institutes of Health (NIH). During her time at the NIH, Dr Cendales established and published a model of VCA in nonhuman primates and has one of the largest experiences in VCA in non-human primates reported in the scientific literature. She organized the first international symposium on VCA histopathology at the International Banff Conferences on Allograft Pathology leading to the published classification system now used as a standard for clinical reporting of rejection. Prior to joining Duke, Dr Cendales established the VCA program at Emory University and led the multi-disciplinary team that performed Georgia's first hand transplant in March 2011. While at Duke, Dr Cendales established the VCA program and led the multi-disciplinary team that performed North Carolina's first hand transplant and first bilateral hand transplant in May 2016 and in November 2018 respectively. Dr Cendales is the Principal Investigator of clinical and translational studies in VCA funded by the U.S. Department of Defense. Dr Cendales is an Associate Editor for the American Journal of Transplantation, is the Chair of the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) Vascularized Composite Allograft (VCA) Committee, and the co-chair elect of the American Transplant Congress, and the Past-President of the International Society of Vascularized Composite Allotransplantation Society (ISVCA). She has co-authored numerous scientific manuscripts, abstracts, and invited publications. Similarly, Dr Cendales has made countless presentations at national and international meetings.

The landscape of vascularized composite allograft donation in the United States.

Vascularized composite allograft (VCA) donation and transplantation has now demonstrated feasibility and impact to the lives of patients suffering from devastating and traumatic injury. This review summarizes the current landscape of VCA donation in the United States. VCA donations are nonlife-saving allografts, for nonlife-saving transplants - and therefore, conservative donor selection focused on the optimization of donors for the lowest risk to transplant recipients is paramount. VCA donors in the United States are a demographically and clinically diverse group that largely reflects the characteristics of the VCA candidates waiting for transplants. Public opinion about VCA donation is generally supportive, but has lower support for VCA transplants than for solid organ transplants. As an emerging area of transplantation, VCA donation is evolving in the United States with growing interest by the public, and those suffering from catastrophic injury for which reconstructive transplantation may offer excellent outcomes and a high quality of life.

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

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. 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. Psychosocial factors hold importance in predicting posttransplant clinical outcomes. Emerging transdiagnostic factors may provide insight into mechanisms and potential treatments.