VCA graft outcomes have improved over time
Sarah Booker, Krissy Laurie, Wida Cherikh, David Klassen and Jennifer Wainright
United Network for Organ Sharing, Richmond, VA, USA
Background: VCA transplantation has advanced considerably since the first U.S. VCA transplant in 1998.
Methods: We analyzed OPTN data for graft and patient outcomes of VCA transplants performed before vs after OPTN oversight of VCA (pre-OPTN: 1/1/1998-7/2/2014; OPTN: 7/3/2014-12/31/2021).
Results: Pre-OPTN transplants included 10 head and neck (HN) (8 face, 2 larynx), 22 upper limb (UL) (9 bilateral, 13 unilateral), and 18 abdominal wall (AW). OPTN transplants included 12 HN (10 face, 1 scalp, 1 trachea), 15 UL (10 bilateral, 5 unilateral), 2 AW, 2 penis, and 33 uterus (21 living donor, 12 deceased donor). The majority of graft failures reported were for pre-OPTN UL (pre-OPTN: 7/22 (31.8%); OPTN: 1/15 (6.7%). Very few graft failures were reported for HN (pre-OPTN: 1/10 (10%); OPTN: 0/12 (0%) or penis (OPTN: 0/2 (0%). For AW, 2/18 (11.1%) pre-OPTN recipients were re-transplanted following solid organ graft failure; AW graft status at time of removal was unknown. No other AW graft failures were reported. For uterus, the majority of graft failures (8/33, 24.2%) were among the earliest U.S. uterus transplants.
Discussion and Conclusion: VCA graft outcomes have improved over time, reflective of advances in the field’s knowledge and experience.
Experimental model of VCA graft vasculopathy and the role of vibrational trauma
Jason Beare1, Yoram Fleissig2, Amanda LeBlanc1 and Christina Kaufman1
1
University of Louisville, Louisville, KY, USA
2
Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel
Introduction: Using an established rat (BN to Lewis) osteomyocutaneous model of VCA with standard immunosuppression, we tested the hypothesis that mechanically induced vibrational trauma will accelerate the development of graft vasculopathy in allogeneic transplant recipients. In our standard immunosuppression model, minimal to mild graft vasculopathy develops over a 60 day period. We show here that mechanically-induced vibration injury exacerbated rejection events as well as both large and small vessel vasculopathy similar to those seen in clinical VCA hand transplant recipients.
Methods: Animals were acclimated prior to treatment and then placed on a TheraPlate Revolution (TheraPlate, Weatherford, TX, USA). Three groups were tested: Allogeneic VCA + 50 Hz vibration, allogeneic VCA + 70 Hz vibration, and non-surgical controls + 50 Hz vibration. All VCA animals received daily immunosuppression (Tacrolimus, 2 mg/kg daily until post-operative day (POD) 11, then 0.5 mg/kg daily until explant). Vibration protocol: 20 min/day, 5 days/week beginning on POD14. Animals were euthanized ~45 days after beginning vibration (POD60-POD62).
Results: Five of six VCA animals exhibited clinical signs of rejection prior to explant. Cell infiltration and intima/medial enlargement in femoral arteries of both vibration groups confirm outward remodeling of the large artery in response to mechanical injury. Microvessels in donor skin showed increased occlusion compared to recipient skin. Normal control animals and contralateral recipient arteries did not show evidence of pathology. Donor vessel intimal hyperplasia correlated with the intensity of the vibration.
Discussion and Conclusion: We have shown previously that standard immunosuppression results in minimal signs of rejection or vasculopathy. Mechanical injury induced via vibration resulted in clinical rejection events, intimal proliferation of donor artery, and overall vasculopathy of both large and small vessels in allogeneic but not contralateral recipient or control animals. Future studies will focus on possible interventions to protect OMC flaps from exacerbation of vasculopathy due to vibrational trauma.
Induction of delayed immune tolerance after reconstructive transplantation by combining donor bone marrow transplantation and high-dose cyclophosphamide treatment
Nathan Katragadda1, Yi-nan Guo1, Franka Messner2, Georg J. Furtmüller3, Yichuan Zhang1, Richa Kalsi3, Amy Bodine1, Alisa Girard1, Isabel Lake1, Damon Cooney1, Leo Luznik1, Byoung Chol Oh1 and Gerald Brandacher1
1
Johns Hopkins School of Medicine, Baltimore, MD, USA
2
Innsbruck Medical University, Innsbruck, Austria
3
University of Maryland Medical Center, Baltimore, MD, USA
Introduction: Immunosuppression avoidance by induction of immune tolerance represents a primary goal in the field of transplantation. Yet, success relies on extensive pre-transplant recipient preconditioning, which is not feasible in VCA. This study explored a novel approach to induce cyclophosphamide-based delayed immune tolerance.
Methods: Orthotopic hindlimb transplantation from Balb/c to C57BL6 was performed. Allografts were maintained with 5 mg/kg Rapamycin until the start of the induction regimen, comprised of non-myeloablative total body irradiation (TBI), anti-thymocyte immune globulin (ATG), and high-dose cyclophosphamide, administered three days after transplantation. Experimental groups involved one (Group 1), ten (Group 2), and thirty-day (Group 3) induction regimen delays post-operation. Additional modifications included donor bone marrow transplantation (dBMT) with or without post-induction ATG and pre-induction fludarabine. Graft survival, chimerism level, and frequency of CD8 memory T cells were assessed. This regimen was translated to a Swine VCA Model involving TBI, ATG, fludarabine, and high-dose cyclophosphamide associated with dBMT on POD 44.
Results: The treatment regimen ± dBMT applied without delay at day 0 led to indefinite graft survival (>250 days) in all VCA recipients (n = 5). In Group 1, delayed induction ± dBMT resulted in indefinite graft survival and a mean survival time (MST) of 88 ± 19.4 d, respectively. In Group 2, the addition of dBMT ± and an additional dose of ATG resulted in indefinite graft survival and an MST of 52.2 ± 18.5 d, respectively. In Group 3, the combination of dBMT, ATG, and fludarabine prolonged graft survival (136 ± 58.0 d vs. 74 ± 7.0 d without ATG and fludarabine). Additional ATG and fludarabine lower the post-induction Tmem proportion in Group 2 and 3 compared without ATG and fludarabine protocol (19.6% ± 15.2% vs. 39.8% ± 25.6 in Group 2, 39.8 ± 25.9% vs. 51% ± 14.45% in Group 3). The translational swine model was applied with the 30-day delayed induction regimen in combination with fludarabine, and additional T cell depletion and rejection was called at POD109.
Discussion and Conclusion: Successful delayed tolerance induction can be achieved in a murine model of hindlimb transplantation with intensified conditioning regimens and is currently being optimized in the VCA swine model.
VCA waiting list and transplant trends in the US
Sarah Booker, Krissy Laurie, Wida Cherikh, David Klassen and Jennifer Wainright
United Network for Organ Sharing, Richmond, VA, USA
Introduction: VCA transplantation is progressing despite challenges including the COVID-19 pandemic.
Methods: The OPTN cohort includes 108 VCA candidates listed and 66 recipients transplanted between 7/3/2014 - 4/30/2022.
Results: Seven VCA candidates were listed in 2021: 3 abdominal wall (AW) and 4 uterus. One AW and 2 uterus candidates were listed in the first 4 months of 2022. AW registrations became the predominant registration type on the VCA waiting list in 2022, surpassing uterus registrations. As of 4/30/2022, the waiting list included 17 candidates: 6 AW, 5 uterus, 4 upper limb (UL; 1 bilateral, 3 unilateral), 1 face, and 1 face/scalp. Since 7/3/2014, 66 recipients received 67 VCA transplants, including 14 UL (9 bilateral, 5 unilateral), 9 face, 1 bilateral UL and face, 1 scalp, 1 trachea, 2 AW, 36 uterus (14 deceased donor, 22 living donor), and 2 penis recipients. In 2021, 1 bilateral UL, 1 trachea, and 2 living donor uterus transplants were performed. In the first 4 months of 2022, 3 uterus transplants (2 deceased donor, 1 living donor) were performed.
Discussion and Conclusion: The composition of the VCA waiting list is changing. VCA transplantation continues to advance despite the COVID-19 pandemic.
The Baltimore criteria for an ethical approach to penile transplantation: An update
Christopher Lopez, Alisa Girard, Isabel Lake, Byoung Chol Oh, Gerald Brandacher, Damon Cooney and Richard Redett
Johns Hopkins School of Medicine, Baltimore, MD, USA
Introduction: Patient selection criteria for penile transplantations remains poorly defined. To address these limitations, our group previously offered ethical guidelines for penile allotransplantation via the Baltimore Criteria. However, it is important to note that the world experience of penile transplantation has not been in accordance with the Baltimore Criteria. Differences in adherence and consideration of outcomes suggest that some criteria may be more important than others. Notable divergences from the Baltimore Criteria with successful outcomes have provided the impetus for an evidence-based update.
Methods: A review of the five penis transplants performed to date was performed. Global updates from the American Society of Reconstructive Transplantation 2021 were included.
Results: Several procedures demonstrated divergence in recipient-donor age guidelines. Given these findings, evidence-based modifications to Baltimore Criteria patient selection are proposed. First, recipients should be adults suffering significant penile loss secondary to traumatic or oncologic etiologies or from congenital anomalies such as ambiguous genitalia or severe micropenis as is often seen in exstrophy-epispadias complex. In the setting of trauma, there should be at least 6 months of recovery time prior to intervention, and in settings of cancer, a remission period consistent with very low risk based on the most current evidence available. There is no waiting period needed for congenital ambiguous genitalia in adults. Second, recipients should be seeking a reconstructive outcome that can only be provided by penile tissue, such as spontaneous erections, capacity for penetrative intercourse, and functional/aesthetic goals that traditional reconstructive modalities cannot achieve. Third, patients and their support systems must undergo rigorous assessment and education and be cleared by their VCA team’s psychological, social, and clinical inclusion criteria. Finally, the deceased donor must a viable, functional graft, and does not require strict age proximity to recipient. While skin tone matching considerations are strongly recommended, if the patient and VCA team feels that a mismatch is outweighed by the potential benefits of transplantation to the individual, proceeding with transplantation should be considered.
Discussion and Conclusion: Evidence-based modifications to the Baltimore Criteria are proposed. Future modifications based on the expanding global experience should be considered.
Empowering patients with upper extremity amputations to communicate with providers about VCA
Jessica Gacki-Smith1, Brianna Kuramitsu1, Max Downey2, Karen Vanterpool2, Michelle Nordstrom3, Michelle Luken4, Tiffany Riggleman4,5, Withney Altema3,5, Shannon Fichter5, Carisa Cooney6, Gregory Dumanian1, Sally Jensen1, Gerald Brandacher6, Scott Tintle5, Macey Levan6 and Elisa Gordon1
1
Northwestern University Feinberg School of Medicine, Chicago, IL, USA
2
NYU Langone Health, New York, NY, USA
3
Uniformed Services University, Bethesda, MD, USA
4
Henry Jackson Foundation, Bethesda, MD, USA
5
Walter Reed National Military Medical Center, Bethesda, MD, USA
6
Johns Hopkins School of Medicine, Baltimore, MD, USA
Introduction: Patient-provider communication can be ineffective because many patients feel intimidated or do not know what questions to ask providers. Many individuals with upper extremity (UE) amputations do not receive sufficient information about their treatment options, particularly vascularized composite allotransplantation (VCA). A question prompt sheet (QPS) is a list of questions that can empower patients to ask questions they find important, promote patient-provider communication, and increase patient knowledge, thereby fostering patient-centered care. This study developed a UE VCA-QPS and examined the UE VCA information needs among people with UE amputations.
Methods: We conducted a multi-site, cross-sectional, sequential mixed-methods study among people with acquired UE amputations. In-depth interviews were first conducted to examine patients’ information needs about UE VCA, which were synthesized through qualitative content analysis into a list of items for the initial UE VCA-QPS draft. The initial draft UE VCA-QPS included 130 items across 18 topics. Thereafter, semi-structured interviews were conducted to rate the importance of each item for inclusion in the VCA-QPS and elicit qualitative rationales for each rating. Quantitative data were analyzed by descriptive statistics. The multidisciplinary research team reviewed the subsequent draft UE VCA-QPS to reduce the number of items, improve wording, remove repetitive items, and ensure that items were clinically relevant.
Results: Eighty-nine people participated (63.9% participation rate), including people who had not pursued UE VCA (85%), UE VCA candidates and participants (9%), and UE VCA recipients (6%). Most were male (73%), White (74%), and had a mean age of 46 years, had a unilateral (84%) and below-elbow amputation (56%). Participants expressed interest in learning about UE VCA eligibility, evaluation process, surgery, risks, rehabilitation, and functional outcomes. The final UE VCA-QPS included 35 items, organized into 9 topics. Items were written at a 6th grade reading level. Most semi-structured interview participants (86%) were ‘completely’ or ‘very’ likely to use a UE VCA-QPS.
Discussion and Conclusion: Our findings suggest that people with UE amputations desire much information about myriad aspects of UE VCA. Future research should assess whether the UE VCA-QPS helps to meet patients’ information needs and foster informed decision-making for UE VCA.
Novel tendon stapler device in wrist level hand allotransplantation
Niki Patel1, John Tipps2, Evelyn Reed3, Russel Hendrycks3, Emily Graham3 and Shaun Mendenhall1,2
1
Children’s Hospital of Philadelphia, Philadelphia, PA, USA
2
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
3
University of Utah School of Medicine, Salt Lake City, UT, USA
Introduction: Vascularized composite hand allotransplantations are time-consuming cases. Surgeons are constantly seeking avenues to reduce operative time for the patient, while also delivering consistent and positive results. A single wrist contains over 20 tendons and can take approximately 90-120 minutes for reattachment in a single hand allotransplantation case. Moreover, results such as repair strength may vary due to surgeon fatigue or suture device failure. A novel tendon stapler device (TSD) has the potential to mitigate these limitations by drastically reducing repair and warm ischemia times, while exhibiting superior biomechanical properties compared to traditional suturing.
Methods: Participants of varying levels of surgical experience performed tendon repairs via suture method or TSD. Six left and right matched human cadaver arms (n = 12) were used for comparisons. Suture repairs were performed using 3.0 braided polyester modified Kessler with a horizontal mattress for a 4-strand repair. On the matched, contralateral donor arms, TSD repairs were completed with a single simple 5.0 polypropylene stitch to approximate the tendon ends prior to device deployment. All repairs were timed by a non-participating data recorder. Immediately following repair, biomechanical properties were tested to compare tensile strength (2 mm gap force) and ultimate failure loads.
Results: A total of 228 tendon repairs from 12 donor arms were analyzed. Mean repair time for a single tendon via suture and TSD repair was 3.9 ± 1.3 and 1.1 ± 0.5 minutes, respectively (p < 0.001). Mean total suture repair time for a single wrist was 102.3 ± 16.0 minutes, while mean TSD repair time was 52.3 ± 12.4 minutes (p < 0.001). Average tensile strength to a 2 mm gap was 29.2 N with suture and 43.0 N with TSD (p < 0.001). Ultimate failure load was 35.19 N with suture and 46.84 N with TSD (p < 0.001). TSD had zero device failures, while standard suture repairs exhibited 30% (n = 34) failures (p < 0.001).
Conclusion: Repairs using TSD versus suture were significantly faster and stronger with each case. Therefore, the advent and use of the novel TSD has the potential to significantly reduce operative time in hand allotransplantation cases, while producing consistent and reliable results.
Human iPSC-derived EGFR+ functional Schwann cells to enhance nerve regeneration and improve functional outcomes in VCA
Amy Bodine, Gabsang Lee, Minseong Kim, Byoung Chol Oh and Gerald Brandacher
Johns Hopkins School of Medicine, Baltimore, MD, USA
Introduction: Nerve regeneration after VCA transplantation using the preferred primary end-to-end nerve repair has few developed novel strategies to increase the speed and degree of nerve regeneration and functionality. Novel stem cell-based therapy of human iPSC-derived Schwann cells post rat forelimb transplantation could improve the regeneration of the median nerve.
Methods: Lewis rats were used to perform median nerve transection and repair as well as full syngeneic forelimb transplants, connecting bone, muscle, brachial vessels, median nerves, and skin to produce a VCA transplant model. All groups received a varying number of human iPSC-derived Schwann cells after transplantation. Grip strength testing, electromyography nerve conduction, and median nerve histomorphometry were used to test the functionalist of the transplant and nerve regeneration/functionality.
Results: 8 rat median nerve cut and repair procedures have been completed. Histomorphometry showed the survival of transplanted GFP-labelled Schwann cells as well as their contribution into myelination structure 1 month after cell transplantation. We are currently analyzing additional in-vivo samples.
Conclusion: Our experiments provide support for the hypothesis that human iPSC-derived Schwann cells could contribute myelination after nerve injury. Treatment of peripheral nerve injury rodent models with human iPSC-derived Schwann cells provide further preliminary support for clinical translation of this treatment modality to promote improved functional recovery following peripheral nerve injury.
Donors’ perceptions of uterus donation motivations, informed consent and value
Anji Wall, Giuliano Testa and Liza Johannesson
Baylor University Medical Center, Dallas, TX, USA
Introduction: Clinical trials have demonstrated the feasibility and reproducibility of uterus transplantation (UTx) to treat absolute uterine factor infertility. Successful live births have resulted from both deceased and living donor uterus transplantation, with more successful recipient pregnancies after living uterus donation. The utilization of living uterus donors for this quality of life-enhancing transplantation remain controversial because of the risks that living uterus donation entails. This study aimed to assess the perceptions of living uterus donors regarding their motivations for donation, perceptions of informed consent, and the value of the uterus donation experience.
Methods: Semi-structured interviews were conducted by phone or in-person of living uterus donors from a single center. Qualitative data were analyzed for themes.
Results: Seventeen of 18 uterus donors consented to participate and completed an interview (94% participation rate). 16/17 were non-directed, and one was directed. Participants were primarily motivated to donate their uterus to give another woman the experience of pregnancy, all felt that informed consent was both accurate and adequate, and all believed that uterus donation had been worthwhile.
Discussion and Conclusion: Uterus donors were highly motivated, well informed, and perceived uterus donation as worthwhile. Our study supports that claim that living donation should remain an option for UTx. More research is needed to determine both the long-term perceptions of uterus donors as well as how donor-recipient relationships and recipient outcomes impact experiences with uterus donation.
Autologous hematopoietic stem cell transplantation prevents antibody-mediated rejection in a swine model of vascularized composite allotransplantation
Amanda Loftin1, Richa Kalsi2, Amy Bodine1, Alisa Girard1, Yichuan Zhang1, Jaimie Shores1, Damon Cooney1, Byoung Chol Oh1 and Gerald Brandacher1
1
Johns Hopkins School of Medicine, Baltimore, MD, USA
2
University of Maryland Medical Center, Baltimore, MD, USA
Introduction: Candidates for vascularized composite allotransplantation (VCA) are frequently sensitized, putting them at risk for antibody-mediated rejection (AMR). The impact of AMR in VCA as well as the cadaveric donor setting will require specifically tailored desensitization strategies and treatment regimens to improve access and outcomes for highly sensitized VCA candidates. The aim of this study is to develop a clinically relevant desensitization protocol utilizing syngeneic hematopoietic stem cell transplantation (HSCT) to prevent AMR in a large animal model for VCA.
Methods: Skin transplants of fully swine leukocyte antigen (SLA) mismatched donor-recipient pairs were performed for sensitization. Heterotopic hind limb transplants in pigs were performed into sensitized recipients or non-sensitized recipients with therapeutic level of Tacrolimus. Clinical examination, serial photodocumentation, and histology of biopsy samples were used to monitor rejection. H&E sections from skin biopsies were assessed for inflammatory infiltration and the presence of intragraft C4d deposition. A novel, clinically relevant desensitization protocol using autologous bone marrow transplants following myeloablative therapy was evaluated. The desensitization protocol consisted of total body irradiation (TBI), fludarabine and autologous HSCT applied to sensitized animals. VCA was then performed four weeks after HSCT and immune reconstitution. Donor specific IgG was measured using flow crossmatch.
Results: Sensitized recipients exhibited accelerated rejection compared to non-sensitized recipients. Serum levels of DSA IgG were markedly elevated in sensitized recipients after VCA and correlated with histological evidence of rejection. Sensitized recipients showed histological evidence of epidermal microhemorrhage after reperfusion, which may represent preformed DSA mediated rejection and correlate with changes to the macroscopic appearance of the skin. Notably, heterotopic swine hindlimb transplantation across a full SLA mismatch combination did not have a rejection episode or evidence of discoloration. In contrast, sensitized animals reject grafts within 9 days under tacrolimus treatment with responsive T-cells pre- and post-transplantation.
Discussion and Conclusion: Sensitization leads to accelerated rejection of VCA, and syngeneic HSCT combined with conventional immunosuppression effectively reduces DSA and improves allograft survival in sensitized a large animal model of VCA. Clinically applicable desensitization protocols are paramount to advancing the field of reconstructive transplantation and critical to improving access to and success of VCA.
Multiplex gene expression analysis reveals distinct rejection patterns in skin and mucosa of facial vascularized composite allotransplants
Martin Kauke-Navarro and Bohdan Pomahac
Yale New Haven Hospital, New Haven, CT, USA
Introduction: Rejection of the facial allograft remains a vexing problem and life-long multidrug immunosuppression is necessary to prevent terminal allograft rejection. Despite rigorous surveillance and immunosuppression protocols both acute and chronic rejection frequently occur. Thus, other tools to adjust and manage immunosuppression are needed. To date, our understanding of rejection in tissues other than skin are limited. The mucosa of facial allografts as a diagnostic tool of whole allograft rejection is poorly studied but it represents another easily accessible tissue for biopsy. Improved understanding of this tissue may help improve longevity of facial allografts, minimize the frequency of acute and chronic rejection, and allow the development of novel revolutionary treatments.
Methods: To better understand the mechanisms underlying mucosal allograft rejection, we studied gene expression profiles of both allograft skin (n = 29) and mucosa (n = 12) at the time of rejection and non-rejection using the NanoString nCounter PanCancer Immune Profiling Gene Expression (GX) CodeSet (NanoString Technologies).
Results: Based on gene expression analysis, we unveil distinct gene signatures of skin and mucosal rejection. Histological assessment and gene signature of mucosal rejection does point towards a significant relevance of B-cells and B-cell function related genes at the time of mucosal rejection when compared to mucosal non-rejection- and skin rejection samples. Skin rejection points towards a predominant role of T-cells.
Conclusion: Skin and mucosal rejection often present at the same time whereas mucosal rejection seems to be more severe compared to concomitantly acquired skin rejection samples. The genetic signature of mucosal rejection may be different from skin rejection. The present study, for the first time, identifies B-cells and B-cell functions as a potential distinguishing feature in mucosal allograft rejection. This may have profound clinical implications as most immunosuppressive regimes target T-cell dependent processes. The role of these cells must be further elucidated to identify function of these cells as a) antibody producing, b) antigen presenting, c) or tolerance inducing immune cells. Improving our understanding of this tissue type may pave the way to developing novel immunomodulatory strategies that may ultimately help extend longevity and functionality of facial allografts.
The first five years of uterus transplant in the United States
Liza Johannesson1, Elliott Richards2, Paige Porrett3, Kathleen O’Neill4 and Giuliano Testa1
1
Baylor University Medical Center, Dallas, TX, USA
2
Cleveland Clinic, Cleveland, Ohio, USA
3
University of Alabama at Birmingham, Birmingham, AL, USA
4
University of Pennsylvania, Philadelphia, PA, USA
Introduction: Uterus transplantation (UTx) is a viable surgical treatment for women affected by absolute uterine-factor infertility, which affects 1 in 500 women. Increased data regarding outcomes following UTx are essential to counsel individuals with AUFI to evaluate all available pathways to parenthood. This cohort-based study aims to review transplant and birth outcomes of UTx in the United States since the first case 5 years ago. The granularity of this report, summarizing the outcomes in the US over the past 5 years, will be instrumental to establish best practices for the development and growth of UTx in the US and abroad.
Methods: We examined donor, recipient, and offspring outcomes following all UTx performed in the US between 2016 and 2021 from the 3 centers performing UTx. The main outcomes and measures included graft survival, live birth, and neonatal outcome.
Results: The mean age of the 33 recipients was 31 ± 4.7 years, and the mean BMI was 24 ± 3.6. Among the 33 recipients, 6% were Asian, 3% were Black, 88% were Caucasian, and 3% were South Asian. Most UTx recipients (31/33, 94%) had a congenitally absent uterus (Mayer-Rokitansky-Küster-Hauser syndrome), and 21/33 (64%) received organs from living donors. Mean follow-up was 36 months (range, 1 to 67 months). There was no donor or recipient mortality. One-year graft survival was 23/31 (74%). Through October 2021, 19/33 (58%) recipients had delivered 21 live-born children. Among recipients with a viable graft at 1 year, the proportion with a live-born child was 83%. The median gestational age at birth of neonates was 36 weeks 6 days (range, 30 weeks 1 day to 38 weeks), and the median birth weight was 2860, corresponding to the 58th percentile (range, 6th to 98th). No congenital malformations were detected.
Discussion and Conclusion: UTx is a surgical therapy that enables women with uterine-factor infertility to successfully gestate and deliver children. Aggregate data from US centers demonstrate safety for the recipient, living donor, and child. These data may be used to counsel women with uterine-factor infertility on treatment options.
7-year outcomes of the first successful pediatric bilateral hand transplantation
Todd Levy1, L. Scott Levin2, Sandra Amaral1,2, Callie Tyner3, Sudha Kessler1 and Debra Lefkowitz1
1
Children’s Hospital of Philadelphia, Philadelphia, PA, USA
2
University of Pennsylvania, Philadelphia, PA, USA
3
University of Delaware, Newark, DE, USA
Introduction: The purpose of this case report is to describe the 7-year functional outcomes and health-related quality of life (HRQOL) of the first successful pediatric bilateral hand transplantation. The report focuses on activity and participation. The authors suggest assessment methods that can be applied to future cases.
Methods: The child underwent quadrimembral amputation at age two years and received bilateral hand allografts at age eight. Rehabilitation included biomechanical, neurorehabilitation, and occupational approaches in acute and outpatient settings. Therapist observed outcomes assessments, patient-reported and parent-reported outcome questionnaires were repeated over a 7-year period.
Results: At 7-years post transplantation, the adolescent and his mother reported a high level of satisfaction with the outcomes. Therapist observed assessments showed the adolescent achieved functional gross motor dexterity with each upper extremity. Although left gross and fine dexterity was superior to the right at all timepoints observed, the adolescent used his right upper extremity as dominant and incorporated both extremities as appropriate for bimanual tasks. The adolescent achieved modified independence to full independence with self-care activities. The adolescent participated in diverse activities with a high level of enjoyment. Participation was more diverse, social, and community-based prior to and after the initial COVID-19 pandemic restrictions. At 7-years post transplantation when the adolescent was 15-years of age, the parent rated more instrumental activities of daily living as somewhat difficult.
Discussion and Conclusion: Therapist observed outcomes assessments, patient-reported and parent-reported outcome questionnaires, showed the child had incorporated his hands into various activities, was completing daily activities independently, and HRQOL outcomes in social, emotional, cognitive, and physical domains were favorable. Most results were stable over time. The decrease in right hand dexterity scores might reflect small kinesiological changes in the right hand. Difficulty with some instrumental activities of daily living were likely due to new activities typical of child development for this now 15-year-old patient.
Biomicroscopy ultrasound of age related vs. Allogeneic vasculopathy in UE-VCA
Christina Kaufman, Allan Ramirez, Huey Tien, Rodrigo Moreno, Michelle Palazzo, Tuna Ozyrekoglu, Bradon Wilhelmi and Christopher Jones
University of Louisville, Louisville, KY, USA
Introduction: We have followed three UE VCA recipients from pre-transplant to 3-10 years post-transplant using Biomicroscopy Ultrasound (Vevo 2100, (FUJIFILM VisualSonics, Toronto, CA) with MS 200 (9-18 MHz) MS400 (13-24 MHz), MS500 (22-55 MHz) and MS700 (30-70 MHz) transducers). In addition, we have data from four UE VCA recipients at timepoints over timeframes of six months to 11 years, with post-transplant timepoints of up to 22 years. We imaged the brachial, radial, ulnar, palmer arch and digital arteries, as well as native contralateral hand (in unilateral recipients). Data was compared to images from an upper extremity replant recipient and normal control subjects.
Methods: Subjects were seated comfortably and had brachial, ulnar, medial, palmar arch and at 2-5 digital arteries scanned using the Vevo 2100 with the highest power probe possible (9-70 MHz), as limited by depth of the target vessel. Prior to scanning digital temperatures were taken to ensure a minimum of 30C°. Vessels were imaged at the same general area for all vessels, with scanning of vessels to screen for changes/thickening, lesions or abnormal architecture. Resolution capabilities of the system prevent scanning of the exact same site on the vessel wall over time without an ultrasound resonant marker.
Results: Age and potentially immunosuppression related changes were observed in artery vessel walls from normal controls and contralateral limbs of transplant and replant recipients. Vasculopathy observed ranged from mild focal non-progressive to confluent thickening restricted to the donor vessels. Calcifications are routinely observed in controls and transplanted patients. We observed frostbite failed to induce significant increases in donor vessel wall thickening as observed by Biomicroscopy Ultrasound even in a recipient with chronic skin rejection.
Discussion and Conclusion: The results demonstrate ease of use and excellent resolution that can be obtained by Biomicroscopy Ultrasound. The technique provides an excellent benchmark of clinically relevant vasculopathy progression, or lack thereof. Our data is primarily from annual visits. For local subjects this technology provides immediately available non-invasive images at a very high resolution that can be used to assess clinical and research interventions, as well as monitoring for risk of ischemic vasculopathy.
Cytomegalovirus-related complications and management in facial VCA: A multicenter study
Martin Kauke-Navarro1, Neil Parikh2, Adriana Panayi3 and Bohdan Pomahac1
1
Yale New Haven Hospital, New Haven, CT, USA
2
Boston University School of Medicine, Boston, MA, USA
3
Brigham and Women’s Hospital, Boston, MA, USA
Introduction: Facial vascularized composite allotransplantation (fVCA) has emerged as a reconstructive option for patients with severe facial deformities. Patients necessarily receive high doses of maintenance immunosuppression to prevent allograft rejection, increasing the risk of developing opportunistic infections. Cytomegalovirus (CMV) is a common opportunistic infection affecting transplant patients. An association between rejection and CMV infection has been made in solid organ transplants. However, a link between CMV infection and acute rejection has yet to be clearly defined in fVCA. We conducted an international multicenter retrospective cohort study and summarized data on CMV-related complications in fVCA patients.
Methods: Patients who underwent face transplantation at one of six participating transplantation centers, representing greater than 40% of FT recipients worldwide, were eligible for inclusion in this study. Standard viral serology screening and testing for transplant candidates was reported, including CMV and Epstein-Barr virus serostatus and the presence of other viruses. Surgery-specific parameters and medication-specific details were extracted. The postoperative periods of follow-up of allograft health in general, as well as CMV occurrence, were recorded. The documented outcomes were CMV-related complications (viremia, disease), allograft-related complications (rejection episodes, graft loss), and mortality.
Results: We included 19 patients, four of whom received CMV high risk transplants (D+/R-). CMV viremia was noted in six patients (all four D+/R- patients and two D-/R+), mostly within the first-year post-transplant, shortly after discontinuation of antiviral prophylaxis (median 2 months). CMV disease occurred in two D+/R- patients. The high-risk group experienced relatively more rejection episodes per month follow-up. None of D+/R– patients suffered allograft loss due to rejection (longest follow-up: 121 months).
Discussion and Conclusion: High risk CMV D+/R– fVCA transplant patients are at increased risk of CMV related complications. Although a higher number of rejections was noted in this group, none of the D+/R– patients lost their allograft or died due to CMV or rejection. CMV viremia/disease was always limited to one episode and followed by seroconversion without evidence of CMV viremia on long-term follow-up. Thus, CMV D+/R– face transplantation can likely be safely performed as long as clinical protocols for CMV prophylaxis, active surveillance, and prompt treatment are in place.
Development of a shared decision making conversation aid for VCA
Ian Hargraves, Kasey Boehmer, Joan Griffin, Cassie Kennedy, Dawn Finnie, Hatem Amer, Fantley Smither, Adam Miller, Karen Schaepe, Victor Montori, Avudaiappan Chokkalingam, and Sheila Jowsey-Gregoire
Mayo Clinic, Rochester, MN, USA
Background: The decision to proceed, or not, with VCA for face or hand transplant is highly complex. Patients and their caregivers require support in thinking, feeling, and talking their way through this decision. A focus on clinical evaluation does not support this need. Shared decision making (SDM) is a process by which patients, clinicians, and care-givers together work to reach a decision that makes sense intellectually, practically, and emotionally. Conversation SDM aids can enable SDM. Our team is developing an online conversation aid for use by hand transplant patients at home and in conversations with their clinicians.
Methods: A user-centered design process was used to develop prototype versions of the conversation aid. These prototypes were informed by IRB-approved:
Interviews with:
• 5 VCA transplant recipients regarding their decision making experience
• 10 potentially eligible VCA transplant recipients regarding perceptions and expectations of VCA
• 21 VCA clinicians regarding VCA practice and patient evaluation
Review of the medical records of (10) patients evaluated for VCA candidacy at an American Academic Medical Center
Results: Medical (e.g., risks of immunosuppression) and nonmedical (e.g., caregiver willingness, practical barriers to undergoing transplant) issues contribute to VCA decisions. Legacy models of SDM are ill-equipped to account for these range of issue types. Purposeful SDM, a novel theoretical model for SDM, that addresses distinct decisional issue types (pros/cons, intra/inter- personal conflicts, problematic situations, and existential matters), guided prototype development.
Conclusion: A prototype online conversation aid has been developed for field testing with patients considering hand transplant.
Patient definitions of transplant “success” of upper extremity VCA
Max Downey1, Jessica Gacki-Smith2, Brianna Kuramitsu2, Karen Vanterpool1, Michelle Nordstrom3, Michelle Luken4, Tiffany Riggleman4,5, Shannon Fichter5, Withney Altema3,5, Whitney Langlee, Carisa Cooney6, Sally Jensen2, Gregory Dumanian2, Macey Levan6, Scott Tintle5, Gerald Brandacher6 and Elisa Gordon5
1
NYU Langone Health, New York, NY, USA
2
Northwestern University Feinberg School of Medicine, Chicago, IL, USA
3
Uniformed Services University, Bethesda, MD, USA
4
Henry Jackson Foundation, Bethesda, MD, USA
5
Walter Reed National Military Medical Center, Bethesda, MD, USA
6
Johns Hopkins School of Medicine, Baltimore, MD, USA
Introduction: Little is known about how to measure the “success” of upper extremity (UE) vascularized composite allotransplantation (VCA), an innovative treatment for people with UE amputations. While providers have defined UE VCA “success” by quantitative functional, clinical, and quality-of-life (QoL) metrics, patients’ definitions are lesser known. Our study assessed patients’ definitions of UE VCA “success.”
Methods: We conducted in-depth interviews and focus groups among people with acquired UE amputations and UE VCA candidates, participants, and recipients at three sites to assess transplant “success” and collect demographic data. Transcripts were analyzed using thematic analysis.
Results: We conducted 50 interviews (61.7% participation rate) and 9 focus groups among 37 participants (75.5% participation rate), including people with acquired UE amputations (83.3%), UE VCA candidates and participants (11.1%), and UE VCA recipients (5.6%). Most were male (73.6%), White (70.8%), had a mean age of 45 years, and had a unilateral (68.1%) and below-elbow amputation (51.4%). Transplant “success” was defined in 6 ways: 1) Restoring function and sensation to enable activities: “I can bring a glass to my lips and drink. I can open a door. . .. I can drive my car” (functional/QoL); 2) Accepting the transplanted limb into the recipient’s identity: “. . .if I can deal with living with it, knowing that it’s not actually my hand” (psychosocial); 3) Surgical attachment of the donor limb to the recipient without rejection: “I’m leaning towards, came out of the surgery, and all the systems are connected” (clinical); 4) Ensuring that the benefits outweigh the risks: “The addition of the functionality would have to outweigh. . . the side-effects of the anti-rejection drugs” (functional/QoL); 5) Attaining better outcomes compared to prosthetics: “. . .if you [are] just having basically a useless limb hanging there. . . it’d be worse than your prosthetic” (functional/QoL).
Conclusion: Our findings suggest that participants have multiple definitions of UE VCA “success” pertaining to improvements in the recipient’s daily living experience, compared to no treatment and/or prosthetics. Informed consent should address whether patients’ desired outcomes can be realized with UE VCA.
