Crowdsourcing Attitudes and Beliefs About Upper Extremity Donation in the United States.

Introduction To date, upper extremity transplantation (UET) is the most frequently performed vascularized composite allotransplantation (VCA). Perceptions regarding upper extremity donation among Americans, particularly in veterans and service members (VSMs), are largely unknown. Materials and methods We administered a one-time survey to United States (US)-resident Amazon Mechanical Turk (MTurk) workers aged ≥18 years. Descriptive statistics were used to summarize study data; frequencies and percentages were calculated for categorical variables analyzed by Fischer's exact test and using a two-tailed test assessing the statistical significance of p<0.05. Results A total of 860 respondents completed the study survey. Among these, 529 (61.5%) reported willingness to donate an upper extremity, 152 (17.7%) were undecided, and 179 (20.8%) were unwilling. A significantly higher proportion of those willing to donate were female (66.7%, p=0.009), non-Hispanic (63.9%, p=0.000), White (64.0%, p=0.004), non-religious (71.3%, p=0.001), not a VSM (62.8%, p=0.000), or non-amputees (62.9%, p=0.000). Conclusions Our survey found that being female, non-Hispanic, White, non-religious, non-VSM, or non-amputee was significantly associated with donation willingness. These findings may help guide VCA programs, organ procurement organizations, and researchers in efforts to develop targeted educational materials to broaden the public's knowledge and awareness of VCA donation to further benefit all patients in need of or desiring transplantation.

Design of a Multiparametric Perfusion Bioreactor System for Evaluating Sub-Normothermic Preservation of Rat Abdominal Wall Vascularized Composite Allografts.

Static cold storage (SCS), the current clinical gold standard for organ preservation, provides surgeons with a limited window of time between procurement and transplantation. In vascularized composite allotransplantation (VCA), this time limitation prevents many viable allografts from being designated to the best-matched recipients. Machine perfusion (MP) systems hold significant promise for extending and improving organ preservation. Most of the prior MP systems for VCA have been built and tested for large animal models. However, small animal models are beneficial for high-throughput biomolecular investigations. This study describes the design and development of a multiparametric bioreactor with a circuit customized to perfuse rat abdominal wall VCAs. To demonstrate its concept and functionality, this bioreactor system was employed in a small-scale demonstrative study in which biomolecular metrics pertaining to graft viability were evaluated non-invasively and in real time. We additionally report a low incidence of cell death from ischemic necrosis as well as minimal interstitial edema in machine perfused grafts. After up to 12 h of continuous perfusion, grafts were shown to survive transplantation and reperfusion, successfully integrating with recipient tissues and vasculature. Our multiparametric bioreactor system for rat abdominal wall VCA provides an advanced framework to test novel techniques to enhance normothermic and sub-normothermic VCA preservations in small animal models.

International consensus recommendations on face transplantation: A 2-step Delphi study.

Face transplantation is a viable reconstructive approach for severe craniofacial defects. Despite the evolution witnessed in the field, ethical aspects, clinical and psychosocial implications, public perception, and economic sustainability remain the subject of debate and unanswered questions. Furthermore, poor data reporting and sharing, the absence of standardized metrics for outcome evaluation, and the lack of consensus definitions of success and failure have hampered the development of a "transplantation culture" on a global scale. We completed a 2-round online modified Delphi process with 35 international face transplant stakeholders, including surgeons, clinicians, psychologists, psychiatrists, ethicists, policymakers, and researchers, with a representation of 10 of the 19 face transplant teams that had already performed the procedure and 73% of face transplants. Themes addressed included patient assessment and selection, indications, social support networks, clinical framework, surgical considerations, data on patient progress and outcomes, definitions of success and failure, public image and perception, and financial sustainability. The presented recommendations are the product of a shared commitment of face transplant teams to foster the development of face transplantation and are aimed at providing a gold standard of practice and policy.

Current opinion: advances in machine perfusion and preservation of vascularized composite allografts - will time still matter?

PURPOSE OF REVIEW: A major hurdle hindering more widespread application of reconstructive transplantation is the very limited cold ischemia time (CIT) of vascularized composite allografts (VCAs). In this review, we discuss cutting edge machine perfusion protocols and preservation strategies to overcome this limitation. RECENT FINDINGS: Several preclinical machine perfusion studies have demonstrated the multifactorial utility of this technology to extend preservation windows, assess graft viability prior to transplantation and salvage damaged tissue, yet there are currently no clinically approved machine perfusion protocols for reconstructive transplantation. Thus, machine perfusion remains an open challenge in VCA due to the complexity of the various tissue types. In addition, multiple other promising avenues to prolong preservation of composite allografts have emerged. These include cryopreservation, high subzero preservation, vitrification and nanowarming. Despite several studies demonstrating extended preservation windows, there are several limitations that must be overcome prior to clinical translation. As both machine perfusion and subzero preservation protocols have rapidly advanced in the past few years, special consideration should be given to their potential complementary utilization. SUMMARY: Current and emerging machine perfusion and preservation technologies in VCA have great promise to transform the field of reconstructive transplantation, as every extra hour of CIT helps ease the complexities of the peri-transplant workflow. Amongst the many advantages, longer preservation windows may allow for elective procedures, improved matching, establishment of novel immunomodulatory protocols and global transport of grafts, ultimately enabling us the ability to offer this life changing procedure to more patients.

Methods of ex vivo analysis of tissue status in vascularized composite allografts.

Vascularized composite allotransplantation can improve quality of life and restore functionality. However, the complex tissue composition of vascularized composite allografts (VCAs) presents unique clinical challenges that increase the likelihood of transplant rejection. Under prolonged static cold storage, highly damage-susceptible tissues such as muscle and nerve undergo irreversible degradation that may render allografts non-functional. Skin-containing VCA elicits an immunogenic response that increases the risk of recipient allograft rejection. The development of quantitative metrics to evaluate VCAs prior to and following transplantation are key to mitigating allograft rejection. Correspondingly, a broad range of bioanalytical methods have emerged to assess the progression of VCA rejection and characterize transplantation outcomes. To consolidate the current range of relevant technologies and expand on potential for development, methods to evaluate ex vivo VCA status are herein reviewed and comparatively assessed. The use of implantable physiological status monitoring biochips, non-invasive bioimpedance monitoring to assess edema, and deep learning algorithms to fuse disparate inputs to stratify VCAs are identified.

Polyethylene Glycol Fusion Restores Axonal Continuity and Improves Return of Function in a Rat Median Nerve Denervation Model.

BACKGROUND: Polyethylene glycol (PEG) can fuse severed closely-apposed axolemmas and restore axonal continuity. We evaluated the effects of PEG-fusion on functional recovery in a rodent forelimb model of peripheral nerve injury. METHODS: The median nerves of male Lewis rats (n=5 per group) were transected and repaired with standard suture repair (SR), SR with PEG (PEG), or SR with PEG and 1% methylene blue (PEG+MB); a sham surgery group was also included. Proximal stimulation produced compound nerve (CAPS) and muscle (CMAPs) action potentials recorded distally. The contralateral limb of each animal acted as an internal control for grip strength measurements. RESULTS: CAPs and CMAPs immediately returned in all PEG and PEG+MB animals, but not in SR animals. PEG and PEG+MB groups demonstrated earlier return of function by post-operative day (POD) 7 (62.6 ±7.3% and 50.9 ±6.7% of contralateral limb grip strength, respectively) compared to SR group, in which minimal return of function was not measurable until POD 21. At POD 98, the PEG group grip strength recovered to 77.2 ±2.8% while the PEG+MB grip strength recovered to 79.9 ±4.4%, compared to 34.9 ±1.8% recovery in the SR group (p<0.05). The PEG and PEG+MB groups reached 50% of the Sham group grip strength on POD 3.8 and 6.3, respectively, whereas the SR group did not reach 50% grip strength recovery of the Sham group throughout the study period. CONCLUSION: PEG-fusion plus neurorrhaphy with or without methylene blue re-established axonal continuity, shortened recovery time, and augmented functional recovery compared to suture neurorrhaphy alone.

The Effects of Growth Hormone on Nerve Regeneration and Alloimmunity in Vascularized Composite Allotransplantation.

BACKGROUND: Poor outcomes in functional recovery following upper extremity transplantation are largely due to denervation-induced muscle atrophy that occurs during the prolonged period of nerve regeneration. Growth hormone (GH) has well-established trophic effects on neurons, myocytes, and Schwann cells and represents a promising therapeutic approach to address this challenge. This study sought to confirm the positive effects of GH treatment on nerve regeneration and functional recovery and to evaluate the effects of GH treatment on the immune response in the setting of vascularized composite allotransplantation. METHODS: Rats underwent orthotopic forelimb transplantation across a full MHC-mismatch and received either porcine-derived growth hormone or no treatment (n=18 per group). Functional recovery was measured using electrically-stimulated grip strength testing. Animals were monitored for clinical and subclinical signs of rejection. RESULTS: Neuromuscular junction reinnervation and grip strength were improved in GH-treated animals (p=0.005; p=0.08). No statistically significant differences were seen in muscle atrophy, degree of myelination, axon diameter, and axon counts between groups. The rates of clinical and histological rejection did not significantly differ among groups. CONCLUSIONS: Our findings alleviate concern for increased risk of transplant rejection during GH therapy and therefore support the translation of growth hormone as a therapeutic method to promote improved functional recovery in upper extremity transplantation.

Ethical and Psychosocial Factors in the Decision-Making and Informed Consent Process for Upper Extremity Vascularized Composite Allotransplantation: A Mixed-Methods Study.

Although upper extremity (UE) vascularized composite allotransplantation (VCA) aims to improve quality of life, relatively few have been performed worldwide to support evidence-based treatment and informed decision-making. Methods: We qualitatively examined factors contributing to anticipated and actual decision-making about UE VCA and perceptions of the elements of informed consent among people with UE amputations, and UE VCA candidates, participants, and recipients through in-depth interviews. Thematic analysis was used to analyze qualitative data. Results: Fifty individuals participated; most were male (78%) and had a mean age of 45 y and a unilateral amputation (84%). One-third (35%) were "a lot" or "completely" willing to pursue UE VCA. UE VCA decision-making themes included the utility of UE VCA, psychosocial impact of UE VCA and amputation on individuals' lives, altruism, and anticipated burden of UE VCA on lifestyle. Most respondents who underwent UE VCA evaluation (n = 8/10) perceived having no reasonable treatment alternatives. Generally, respondents (n = 50) recognized the potential for familial, societal, cultural, medical, and self-driven pressures to pursue UE VCA among individuals with amputations. Some (n = 9/50, 18%) reported personally feeling "a little," "somewhat," "a lot," or "completely" pressured to pursue UE VCA. Respondents recommended that individuals be informed about the option of UE VCA near the amputation date. Conclusions: Our study identified psychosocial and other factors affecting decision-making about UE VCA, which should be addressed to enhance informed consent. Study participants' perceptions and preferences about UE VCA suggest re-examination of assumptions guiding the UE VCA clinical evaluation process.

Patient definitions of transplant success in upper extremity vascularized composite allotransplantation: A mixed-methods study.

Objective: Upper extremity vascularized composite allotransplantation is an innovative treatment option for people with upper extremity amputations. Limited patient-relevant long-term outcomes data about transplant success may impede patients' informed treatment decision-making. We assessed perceptions of what constitutes upper extremity vascularized composite allotransplantation success among individuals with upper extremity amputations. Methods: This multisite study entailed interviews and focus groups with individuals with upper extremity amputations and upper extremity vascularized composite allotransplantation candidates, participants, and recipients. We examined perceptions of transplant success and preferences for five upper extremity vascularized composite allotransplantation outcomes. Qualitative data were analyzed using thematic analysis; and quantitative data were analyzed using descriptive statistics. Results: In all, 50 individuals participated in interviews (61.7% participation rate), and 37 participated in nine focus groups (75.5% participation rate). Most were White (72%, 73%), had a mean age of 45 and 48 years, and had a unilateral amputation (84%, 59%), respectively. Participants conceptualized upper extremity vascularized composite allotransplantation success as transplant outcomes: (1) restoring function and sensation to enable new activities; (2) accepting the transplanted limb into one's identity and appearance; (3) not having transplant rejection; (4) attaining greater quality of life compared to prosthetics; and (5) ensuring benefits outweigh risks. Participants rated their most important upper extremity vascularized composite allotransplantation outcomes as follows: not having transplant rejection, not developing health complications, grasping objects, feeling touch and temperature, and accepting the upper extremity vascularized composite allotransplantation into your identity. Conclusion: Individuals with upper extremity amputations maintain several conceptions of vascularized composite allotransplantation success, spanning functional, psychosocial, clinical, and quality of life outcomes. Providers should address patients' conceptions of success to improve informed consent discussions and outcomes reporting for upper extremity vascularized composite allotransplantation.

Patient preferences of patient selection criteria for upper extremity vascularized composite allotransplantation: A qualitative study.

Background: Upper extremity vascularized composite allotransplantation is a life-enhancing reconstructive treatment option that aims to improve recipients' quality of life and maximize function. This study assessed upper extremity vascularized composite allotransplantation patient selection criteria perceptions among individuals with upper extremity limb loss. The perceptions of individuals with upper extremity limb loss on patient selection criteria may enable vascularized composite allotransplantation centers to improve criteria to avoid mismatched expectations about the posttransplant vascularized composite allotransplantation experience and outcomes. Realistic patient expectations may increase patient adherence, improve outcomes, and reduce vascularized composite allotransplantation graft loss. Methods: We conducted in-depth interviews with civilian and military service members with upper extremity limb loss and upper extremity vascularized composite allotransplantation candidates, participants, and recipients from three US institutions. Interviews assessed perceptions of patient selection criteria for suitability as a candidate for upper extremity vascularized composite allotransplantation. Thematic analysis was used to analyze qualitative data. Results: A total of 50 individuals participated (66% participation rate). Most participants were male (78%), White (72%), with a unilateral limb loss (84%), and a mean age of 45 years. Six themes emerged regarding upper extremity vascularized composite allotransplantation patient selection criteria, including support for candidates who: (1) are of younger age, (2) are in good physical health, (3) have mental stability, (4) are willing to "put in the work," (5) have specific amputation characteristics, and (6) have sufficient social support. Patients had preferences about selecting candidates with unilateral versus bilateral limb loss. Conclusions: Our findings suggest that numerous factors, including medical, social, and psychological characteristics, inform patients' perceptions of patient selection criteria for upper extremity vascularized composite allotransplantation. Patient perceptions of patient selection criteria should inform the development of validated screening measures that optimize patient outcomes.

A Novel Sutureless Anastomotic Device in a Swine Model: A Proof of Concept Study.

INTRODUCTION: Vascular reconstruction requires technical expertise and is often time consuming. As a novel alternative to traditional hand-sewn vascular anastomoses, the VasoLock (VL), is a nonabsorbable, sutureless anastomosis device with traction anchors designed to hold free artery ends together. These anchors do not penetrate the vessel wall but adhere by leveraging the elasticity of the vessels to fasten blood vessels together. This pilot study assesses the performance and patency of this novel device in a porcine model of femoral artery injury. METHODS: Female swine (n = 7) underwent femoral artery exposure for a total of 10 VL implanted. Study animals underwent hemodilution to a target hematocrit of 15% and ROTEM was used to assess coagulopathy, followed by an arterial injury via transection. The VL was inserted without any sutures. Flow-probe monitors were positioned proximal and distal to the device and flow rates were measured continuously for a total of 90 min. Flow was analyzed and presented as a ratio of distal to proximal flow with the slope of this ratio across time subsequently determined. Angiographic assessment was completed to evaluate for patency and technical complications after 90 min of implant. RESULTS: The average animal weight was 44.1 ± 3.2 kg. The average mean arterial pressure at the time of implant was 51.2 ± 7.8 mmHg, median heart rate was 77.4 (IQR = 77.25-157.4) beats per minute, and average temperature was 36.1 ± 1.5°C. The baseline hematocrit was 13.5 ± 3.0%, average pH was 7.20 ± 0.1, average clotting time was 154.1 ± 58.7 s and average clot formation time was 103.4 ± 10.9 s all demonstrating the acidotic, hypothermic, and coagulopathic state of the swine at the time of insertion. During the 90-min observation period, the average flow gradient identified across the VL was 0.99 ± 0.24, indicating no significant change in flow across the VL. The average slope of the gradients was 0.0005 (P = 0.22), suggesting the ratio of proximal and distal flow did not change over the 90 min. Following 90 min of dwell time, all VL were patent without technical complication. Angiographic assessment at 90 min demonstrated no evidence of dissection, device migration, arterial extravasation, or thromboembolism with any of the 10 devices. CONCLUSIONS: This pilot study demonstrated technical feasibility of the novel VL device over a 90-min observation period. All VL were patent and no negative events or complications were identified. This technology demonstrated significant promise in a coagulopathic state: additional investigation, involving long-term survival, is warranted for further validation.

Biomaterials-based immunomodulation enhances survival of murine vascularized composite allografts.

Vascularized composite allotransplantation (VCA) is a restorative option for patients suffering from severe tissue defects not amenable to conventional reconstruction. However, the toxicities associated with life-long multidrug immunosuppression to enable allograft survival and induce immune tolerance largely limit the broader application of VCA. Here, we investigate the potential of targeted immunomodulation using CTLA4-Ig combined with a biological porcine-derived extracellular matrix (ECM) scaffold that elicits a pro-regenerative Th2 response to promote allograft survival and regulate the inflammatory microenvironment in a stringent mouse orthotopic hind limb transplantation model (BALB/c to C57BL/6). The median allograft survival time (MST) increased significantly from 15.0 to 24.5 days (P = 0.0037; Mantel-Cox test) after adding ECM to the CTLA4-Ig regimen. Characterization of the immune infiltration shows a pro-regenerative phenotype prevails over those associated with inflammation and rejection including macrophages (F4/80hi+CD206hi+MHCIIlow), eosinophils (F4/80lowSiglec-F+), and T helper 2 (Th2) T cells (CD4+IL-4+). This was accompanied by an increased expression of genes associated with a Type 2 polarized immune state such as Il4, Ccl24, Arg1 and Ym1 within the graft. Furthermore, when ECM was applied along with a clinically relevant combination of CTLA4-Ig and Rapamycin, allograft survival was prolonged from 33.0 to 72.5 days (P = 0.0067; Mantel-Cox test). These studies implicate the clinical exploration of combined regimens involving local application of pro-regenerative, immunomodulatory biomaterials in surgical wound sites with targeted co-stimulatory blockade to reduce adverse effects of immunosuppression and enhance graft survival in VCA.

Real-Time Monitoring Using Multiplexed Multi-Electrode Bioelectrical Impedance Spectroscopy for the Stratification of Vascularized Composite Allografts: A Perspective on Predictive Analytics.

Vascularized composite allotransplantation addresses injuries to complex anatomical structures such as the face, hand, and abdominal wall. Prolonged static cold storage of vascularized composite allografts (VCA) incurs damage and imposes transportation limits to their viability and availability. Tissue ischemia, the major clinical indication, is strongly correlated with negative transplantation outcomes. Machine perfusion and normothermia can extend preservation times. This perspective introduces multiplexed multi-electrode bioimpedance spectroscopy (MMBIS), an established bioanalytical method to quantify the interaction of the electrical current with tissue components, capable of measuring tissue edema, as a quantitative, noninvasive, real-time, continuous monitoring technique to provide crucially needed assessment of graft preservation efficacy and viability. MMBIS must be developed, and appropriate models explored to address the highly complex multi-tissue structures and time-temperature changes of VCA. Combined with artificial intelligence (AI), MMBIS can serve to stratify allografts for improvement in transplantation outcomes.

Hickman Catheter Use for Long-Term Vascular Access in a Preclinical Swine Model.

Central venous catheters (CVCs) are invaluable devices in large animal research as they facilitate a wide range of medical applications, including blood monitoring and reliable intravenous fluid and drug administration. Specifically, the tunneled multi-lumen Hickman catheter (HC) is commonly used in swine models due to its lower extrication and complication rates. Despite fewer complications relative to other CVCs, HC-related morbidity presents a significant challenge, as it can significantly delay or otherwise negatively impact ongoing studies. The proper insertion and maintenance of HCs is paramount in preventing these complications, but there is no consensus on best practices. The purpose of this protocol is to comprehensively describe an approach for the insertion and maintenance of a tunneled HC in swine that mitigates HC-related complications and morbidity. The use of these techniques in >100 swine has resulted in complication-free patent lines up to 8 months and no catheter-related mortality or infection of the ventral surgical site. This protocol offers a method to optimize the lifespan of the HC and guidance for approaching issues during use.

Donor derived hematopoietic stem cell niche transplantation facilitates mixed chimerism mediated donor specific tolerance.

Compelling experimental evidence confirms that the robustness and longevity of mixed chimerism (MC) relies on the persistence and availability of donor-derived hematopoietic stem cell (HSC) niches in recipients. Based on our prior work in rodent vascularized composite allotransplantation (VCA) models, we hypothesize that the vascularized bone components in VCA bearing donor HSC niches, thus may provide a unique biologic opportunity to facilitate stable MC and transplant tolerance. In this study, by utilizing a series of rodent VCA models we demonstrated that donor HSC niches in the vascularized bone facilitate persistent multilineage hematopoietic chimerism in transplant recipients and promote donor-specific tolerance without harsh myeloablation. In addition, the transplanted donor HSC niches in VCA facilitated the donor HSC niches seeding to the recipient bone marrow compartment and contributed to the maintenance and homeostasis of stable MC. Moreover, this study provided evidences that chimeric thymus plays a role in MC-mediated transplant tolerance through a mechanism of thymic central deletion. Mechanistic insights from our study could lead to the use of vascularized donor bone with pre-engrafted HSC niches as a safe, complementary strategy to induce robust and stable MC-mediated tolerance in VCA or solid organ transplantation recipients.

A Patient-Centered Website (Within Reach) to Foster Informed Decision-making About Upper Extremity Vascularized Composite Allotransplantation: Development and Usability Study.

BACKGROUND: Upper extremity (UE) vascularized composite allotransplantation (VCA; hand transplantation) is a reconstructive treatment option for patients with UE loss. Approximately 37 UE VCAs have been performed in the United States to date; thus, little is known about long-term psychosocial outcomes and whether the benefits outweigh the risks. To make an informed treatment decision, patients must understand the procedure, risks, and potential benefits of UE VCA. However, few educational resources are publicly available providing unbiased, comprehensive information about UE VCA. OBJECTIVE: This paper described the development of a neutral, and accessible, educational website supporting informed decision-making about UE VCA as a treatment option for individuals with UE amputations. METHODS: Website content development was informed by 9 focus groups conducted with individuals with UE amputations at 3 study sites. After initial website development, we conducted usability testing to identify ways to improve navigability, design, content, comprehension, and cultural sensitivity. Participants were administered the After-Scenario Questionnaire to assess user performance after completing navigational tasks, System Usability Scale to measure the perceived usability of the website, and Net Promoter Score to measure user satisfaction. Quantitative data were analyzed using descriptive statistics. Qualitative data were analyzed using rapid thematic analysis. RESULTS: A total of 44 individuals with UE amputations participated in focus groups (n=37, 84%) and usability testing (n=14, 32%). Most participants in the focus groups and usability testing were male (24/37, 65% and 11/14, 79%, respectively) and White (27/37, 73% and 9/14, 64%, respectively), had unilateral limb loss (22/37, 59% and 12/14, 86%, respectively), and had mean ages of 48 (SD 9.2) and 50 (SD 12.0) years, respectively. Focus group results are organized into accessibility, website design, website development, website tone and values, sitemap, terminology, images and videos, and tables and graphics. Usability testing revealed that participants had a positive impression of the website. The mean After-Scenario Questionnaire score of 1.3 to 2.3 across task scenarios indicated high satisfaction with website usability, the mean System Usability Scale score of 88.9 indicated user satisfaction with website usability, and the mean Net Promoter Score of 9.6 indicated that users were enthusiastic and would likely refer individuals to the website. CONCLUSIONS: The findings suggest that our educational website, Within Reach, provides neutral, patient-centered information and may be a useful resource about UE VCA for individuals with UE amputations, their families, and health care professionals. Health care professionals may inform UE VCA candidates about Within Reach to supplement current VCA education processes. Within Reach serves as a resource about treatment options for patients preparing for scheduled or recovering from traumatic UE amputations. Future research should assess whether Within Reach improves knowledge about UE VCA and enhances informed decision-making about UE VCA as a treatment option.

Lessons learned from the first 15 years of penile transplantation and updates to the Baltimore Criteria.

Since 2006, five penis transplants have been performed worldwide. Mixed outcomes have been reported, and two of the five penile transplants have required explantation. However, the long-term outcomes have been encouraging when compliance is implemented, whether standard induction and triple therapy maintenance, or single therapy maintenance. Follow-up monitoring of transplant recipients has enabled a synthesis of technical considerations for surgical success and has shown stable leukocyte counts and renal function after a donor bone-marrow-based immunomodulatory regimen followed by tacrolimus monotherapy as long as 3 years post-transplant, as well as continuous nerve regeneration of penile allografts 3 years post-transplant. Areas of uncertainty include the ethics of donor-recipient colour mismatch, surveillance for sexually transmitted infections and how to optimize patient compliance. Questions also remain with respect to the long-term immunological sequelae of penile tissue, functional outcomes, psychosocial implications and patient selection. Patient counselling should be modified to mention the possibility of long-term improvement in nerve regeneration and sufficient renal function with single-therapy maintenance, and to build a longitudinal dialogue and partnership between the patient and the multidisciplinary care team regarding the risks of sexually transmitted infection instead of surveillance.

Identifying Health-Related Quality of Life Domains After Upper Extremity Transplantation.

OBJECTIVE: To identify the most important health-related quality of life (HRQOL) domains and patient-reported outcomes after upper extremity transplantation (UET) in individuals with upper extremity amputation. DESIGN: Verbatim audio-recordings of individual interviews and focus groups were analyzed using qualitative, grounded theory-based methods to identify important domains of HRQOL and provide guidance for outcomes measurement after UET. SETTING: Individual interviews were conducted by phone. Focus groups were conducted at 5 upper extremity vascularized composite allotransplantation (VCA) centers in the US and at an international conference of VCA experts. PARTICIPANTS: Individual phone interviews were conducted with 5 individuals with lived experience of UET. Thirteen focus groups were conducted with a total of 59 clinical professionals involved in UET. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Twenty-eight key HRQOL domains were identified, including physical functioning and medical complications, positive and negative emotional functioning, and social participation, relations, and independence. We identified key constructs for use in evaluation of the potentially substantial physical, medical, social, and emotional effects of UET. CONCLUSIONS: This study provides an overview of the most important issues affecting HRQOL after UET, including several topics that are unique to individuals with UET. This information will be used to establish systematic, comprehensive, and longitudinal measurement of post-UET HRQOL outcomes.

Development of a rat forelimb vascularized composite allograft (VCA) perfusion protocol.

Vascularized composite allografts (VCAs) refer to en bloc heterogenous tissue that is transplanted to restore form and function after amputation or tissue loss. Rat limb VCA has emerged as a robust translational model to study the pathophysiology of these transplants. However, these models have predominately focused on hindlimb VCAs which does not translate anatomically to upper extremity transplantation, whereas the majority of clinical VCAs are upper extremity and hand transplants. This work details our optimization of rat forelimb VCA procurement and sub-normothermic machine perfusion (SNMP) protocols, with results in comparison to hindlimb perfusion with the same perfusion modality. Results indicate that compared to hindlimbs, rat forelimbs on machine perfusion mandate lower flow rates and higher acceptable maximum pressures. Additionally, low-flow forelimbs have less cellular damage than high-flow forelimbs based on oxygen uptake, edema, potassium levels, and histology through 2 hours of machine perfusion. These results are expected to inform future upper extremity VCA preservation studies.

Public Perceptions and Information Needs of VCA Transplantation and Donation: A Mixed Methods Study.

Vascularized Composite Allotransplantation (VCA) involves transplantation of multiple tissues from a donor to a recipient (e.g., skin, muscle, bone). Little is known about the US public's perceptions of and attitudes toward VCA organ donation. This multi-site, cross-sectional, mixed methods study involved focus groups and surveys to assess members of the general public's attitudes about VCA, and willingness and barriers to donate VCA organs. Qualitative data were analyzed by thematic analysis; quantitative data were analyzed by descriptive statistics. In focus groups (n = 6, 42 participants), most participants were female (57%) and Black (62%) with mean age of 42.6 years. Three main themes emerged: 1) awareness and perceptions of VCA, 2) purpose of VCA donation, 3) and barriers to VCA donation. Participants had heard little about VCA and sought information about VCA donation. Participants perceived VCA as challenging their concepts of "normality" and voiced concerns that VCA would create "Frankenstein[s]." Barriers to VCA donation included disruptions to end-of-life arrangements and information gaps regarding the donation process. Participants reported moderate to high willingness to donate their hands (69%) and face (50%) Public education efforts should address the specific needs and concerns of the public to facilitate VCA donation and family authorization.