Advancing vascularized composite allotransplantation: essential factors for upper extremity transplant program development.

Vascularized Composite Allotransplantation (VCA) offers a unique option to restore form and function after limb loss or facial trauma that cannot be satisfactorily accomplished through traditional prosthetics or reconstructions. Establishing a successful Upper Extremity Transplantation (UET) program requires strong leadership and a structured surgical team, and extensive interdisciplinary collaboration. We conducted a qualitative study among 12 health care professionals and patients. Informed consent was obtained per protocol, and semi-structured interviews were conducted online and recorded. Participants reported their perceptions of factors that either favored or hindered a successful outcome, including functional status before and after surgery, preparation for transplant, shared decision-making, rehabilitation, and psychosocial support. Thematic analysis revealed that it is essential to establish a team comprising various disciplines well before performing VCA procedures. Defining a common goal and choosing a defined leader is a key factor in procedural success and requires open collaboration beyond what is typical. Primary described categories are interdisciplinary collaboration and skills of the VCA team, building and leading a VCA team, pre-transplant procedures, post-transplant course, and factors to consider when establishing a program. The basic roles of team science play an outsized role in establishing a VCA program. Transplantation medicine involves various overlapping scientific and medical categories requiring health professionals to consciously work together to establish complex vertical and horizontal communication webs between teams to obtain positive outcomes. In addition to medical considerations, patient-specific factors such as transparent communication, therapy plan establishment, plan adherence, and continual follow-up are significant factors to overall success.

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.

Crowdsourcing Opinions and Awareness of Upper Extremity Transplantation in the United States.

Introduction As of 2008, the United States had 41,000 people living with upper extremity amputation. This number is projected to reach 300,000 by 2050. Human upper extremity transplantation (HUET) may become a more common treatment option with the potential to significantly improve the quality of life for certain amputees. Awareness and opinions regarding HUET among Americans, particularly in Veterans/Service Members (VSM) affiliates, are largely unknown. Materials and methods We administered a survey on Amazon Mechanical Turk (MTurk) workers. Eligible participants were US citizens aged ≥18 years; MTurk worker selection targeted workers who self-reported being a VSM. We used descriptive statistics to summarize study findings and Fisher's exact and Wilcoxon's rank-sum tests for between-group comparisons. Results The survey was completed by 764 individuals, 604 (79.1%) of whom reported being aware of HUET. Among those familiar versus unfamiliar, a significantly higher proportion were aged ≤35 years (n=385, 64.0% vs. n=86, 53.7%; p=0.017), employed (n=523, 86.6% vs. n=114, 71.3%; p<0.001), and aware of their religion's stance on organ/tissue donation (n=341, 54.5% vs. n=62, 38.8%; p<0.001). Amputees and/or respondents related to an amputee were more likely to be aware of HUET than individuals who were amputation naive (n=211, 90.6% vs. n=393, 74.0%, respectively; p<0.001), as were individuals with a personal or familial military affiliation (n=286, 85.4% with vs. n=318, 74.1% with no affiliation; p<0.001). The most reported HUET information sources were digital media (n=157, 31.2%) and internet (n=137, 27.2%). Conclusions Our survey of MTurk workers found greater awareness of HUET among individuals with a VSM or amputee connection. Our additional findings that the internet and academic sources, such as journals or reputable medical publications, were respondents' preferred sources of HUET information emphasize the importance of vascularized composite allotransplantation (VCA) centers' involvement in creating accurate and accessible content to help educate the public about this treatment.

T cell-attracting CCL18 chemokine is a dominant rejection signal during limb transplantation.

Limb transplantation is a life-changing procedure for amputees. However, limb recipients have a 6-fold greater rejection rate than solid organ transplant recipients, related in part to greater immunogenicity of the skin. Here, we report a detailed immunological and molecular characterization of individuals who underwent bilateral limb transplantation at our institution. Circulating Th17 cells are increased in limb transplant recipients over time. Molecular characterization of 770 genes in skin biopsies reveals upregulation of T cell effector immune molecules and chemokines, particularly CCL18. Skin antigen-presenting cells primarily express the chemokine CCL18, which binds to the CCR8 receptor. CCL18 treatment recruits more allo-T cells to the skin xenograft in a humanized skin transplantation model, leading to signs of accelerated graft rejection. Blockade of CCR8 remarkedly decreases CCL18-induced allo-T cell infiltration. Our results suggest that targeting the CCL18:CCR8 pathway could be a promising immunosuppressive approach in transplantation.

Graft vasculopathy in upper extremity allotransplantation: Results of a retrospective high-resolution ultrasonographic study.

Graft vasculopathy (GV) is the most severe pathologic change of chronic rejection in vascularized composite allotransplantation. Since 2012, the intimal media thickness (IMT) of radial and ulnar arteries was annually monitored by high-resolution ultrasonography in seven bilateral upper extremity transplant (UET) patients. We also investigated the IMT of seven matched healthy subjects (controls). No significant difference between IMT values of controls and UET patients was found. The median IMT values of recipient radial and ulnar arteries were 0.23 mm and 0.25 mm, respectively, while the median IMT values of grafted radial and ulnar arteries were 0.27 mm and 0.30 mm, respectively. There was a statistically significant difference in the IMT values of the grafted and recipient ulnar arteries (p = .043), but this difference was no longer significant when patient #2 was excluded. He showed a significant difference between recipient and grafted arteries and significantly higher IMT values (p = .001) of his grafted arteries compared with those of all transplanted patients. This patient developed GV leading to graft loss 11 years after the transplantation. In conclusion, this study showed a significant IMT increase in an UET recipient who developed GV.

Vascularized composite allotransplantation - a Council of Europe position paper.

After more than 120 hand-upper extremity and 37 face transplant procedures performed worldwide, vascularized composite allotransplantation (VCA) now falls under the scope of organ transplant legislation in Europe and the United States. While in the USA, VCA has been considered as standard care since 2014, VCA in Europe is still performed through clinical research trials, except in United Kingdom. However, after two decades of favourable experience with upper extremity transplantation (UET), professionals in Europe are proposing hand allotransplantation as "controlled standard" care, as opposed to face transplantation (FT), which is still a challenging activity. The European Committee on Organ Transplantation (CD-P-TO) has elaborated a position paper to provide recommendations concerning regulatory aspects for UET and FT. It is aimed at Health Authorities in charge of the oversight - and coordination - of organ donation and transplantation, and at professional groups to help them manage such complex and costly programs dedicated to properly selected patients.

Experience With Patient Referrals for Upper Extremity Transplantation at a U.S. Academic Medical Center.

PURPOSE: To date, there have been over 100 upper extremity transplantations (UET) performed worldwide. However, little data are available regarding institutional screening practices or description of the population of patients that seek transplantation as a treatment modality for their upper extremity disabilities. We performed a review of our institutional experience in an attempt to better understand our referral patterns and identify factors that may be associated with successful screening. METHODS: Contact demographic data, injury characteristics, and mode of referral were retrospectively reviewed from 2010 through 2015. Differences in demographic data, injury-related characteristics, and clinical trial outcomes were assessed with the Chi-square test or Fisher exact test. RESULTS: There were a total of 89 UET contacts. The average age was 35.2 years, with most contacts being white (n = 24). The majority were male (n = 66; 75.0%) and the most common indication for referral was trauma (n = 43; 55.8%). Of the 89 contacts, 20 (22.5%) were physician referrals and 69 (77.5%) were self-referrals. Physician referrals led to the most screened and accepted contacts, whereas self-referrals more often led to immediate exclusion. CONCLUSIONS: This study gives an overview of the demographic composition of our UET contacts, with a specific emphasis on mode of referral. We have identified that physician referrals have led to more screened and accepted patients versus self-referred individuals. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.