Vascularized Composite Allografts Research Articles

Impact of removing OPTN region from vascularized composite allograft allocation

On 6/18/2020, the Organ Procurement and Transplantation Network (OPTN) implemented new policy replacing OPTN region with a 500 nautical mile (NM) circle around the donor hospital for the purpose of vascularized composite allograft (VCA) allocation. We used OPTN data to assess deceased donor VCA transplants in the 3 years pre- (6/19/2017–6/17/2020) vs. post-implementation (6/18/2020–6/17/2023). A total of 19 deceased donor VCA transplants were performed pre-policy (10 uterus, 3 bilateral upper limb, 1 unilateral upper limb, 3 face, 1 abdominal wall and 1 penis), and 11 post-policy (4 uterus, 1 bilateral upper limb, 2 face, 1 trachea, 2 abdominal wall, and 1 bilateral upper limb and face). Median distance from donor hospital to transplant hospital increased from 70 NM (range: 0–524 NM) pre-policy to 119 NM (range: 0–464 NM) post-policy. The majority of transplants in both policy eras were within 500 NM of the donor hospital [89.5% (N = 17/19) vs. 100% (N = 11/11)] and most remained within the same OPTN region as the donor hospital [68.4% (N = 13/19) vs. 90.9% (N = 10/11)]. Although it is difficult to draw strong conclusions about the policy's impact due to the low transplant volume and timing of implementation relative to the COVID-19 pandemic, data in the 3 years post-implementation suggest that 500 NM circles were a reasonable replacement for OPTN region in VCA allocation. The OPTN will continue to review data to monitor the policy's impact and inform future changes to VCA allocation, such as the transition to continuous distribution, a points-based framework expected to replace the current framework.

Machine Perfusion Enables 24-h Preservation of Vascularized Composite Allografts in a Swine Model of Allotransplantation

The current gold standard for preserving vascularized composite allografts (VCA) is 4°C static cold storage (SCS), albeit muscle vulnerability to ischemia can be described as early as after 2 h of SCS. Alternatively, machine perfusion (MP) is growing in the world of organ preservation. Herein, we investigated the outcomes of oxygenated acellular subnormothermic machine perfusion (SNMP) for 24-h VCA preservation before allotransplantation in a swine model. Six partial hindlimbs were procured on adult pigs and preserved ex vivo for 24 h with either SNMP (n = 3) or SCS (n = 3) before heterotopic allotransplantation. Recipient animals received immunosuppression and were followed up for 14 days. Clinical monitoring was carried out twice daily, and graft biopsies and blood samples were regularly collected. Two blinded pathologists assessed skin and muscle samples. Overall survival was higher in the SNMP group. Early euthanasia of 2 animals in the SCS group was linked to significant graft degeneration. Analyses of the grafts showed massive muscle degeneration in the SCS group and a normal aspect in the SNMP group 2 weeks after allotransplantation. Therefore, this 24-h SNMP protocol using a modified Steen solution generated better clinical and histological outcomes in allotransplantation when compared to time-matched SCS.

Effect of Subnormothermic Machine Perfusion on the Preservation of Vascularized Composite Allografts After Prolonged Warm Ischemia.

Warm ischemia time (WIT) and ischemia-reperfusion injury are limiting factors for vascularized composite allograft (VCA) transplantation. Subnormothermic machine perfusion (SNMP) has demonstrated the potential to extend WIT in organ transplantation. This study evaluates the effect of SNMP on VCA viability after prolonged WIT. Rat hindlimbs underwent WIT for 30, 45, 60, 120, 150, or 210 min, followed by 3-h SNMP. Monitoring of perfusion parameters and outflow determined the maximum WIT compatible with limb viability after SNMP. Thereafter, 2 groups were assessed: a control group with inbred transplantation (Txp) after 120 min of WIT and an experimental group that underwent WIT + SNMP + Txp. Graft appearance, blood gas, cytokine levels, and histology were assessed for 21 d. Based on potassium levels, the limit of WIT compatible with limb viability after SNMP is 120 min. Before this limit, SNMP reduces potassium and lactate levels of WIT grafts to the same level as fresh grafts. In vivo, the control group presented 80% graft necrosis, whereas the experimental group showed no necrosis, had better healing (P = 0.0004), and reduced histological muscle injury (P = 0.012). Results of blood analysis revealed lower lactate, potassium levels, and calcium levels (P = 0.048) in the experimental group. Both groups presented an increase in interleukin (IL)-10 and IL-1b/IL-1F2 with a return to baseline after 7 to 14 d. Our study establishes the limit of WIT compatible with VCA viability and demonstrates the effectiveness of SNMP in restoring a graft after WIT ex vivo and in vivo, locally and systemically.

Exploring Iodide and Hydrogen Sulfide as ROS Scavengers to Delay Acute Rejection in MHC-Defined Vascularized Composite Allografts.

Vascularized composite allografts (VCA) face ischemic challenges due to their limited availability. Reperfusion following ischemia triggers oxidative stress and immune reactions, and scavenger molecules could mitigate ischemia-reperfusion injuries and, therefore, immune rejection. We compared two scavengers in a myocutaneous flap VCA model. In total, 18 myocutaneous flap transplants were performed in Major histocompatibility complex (MHC)-defined miniature swine. In the MATCH group (n = 9), donors and recipients had minor antigen mismatch, while the animals were fully mismatched in the MISMATCH group (n = 9). Grafts were pretreated with saline, sodium iodide (NaI), or hydrogen sulfide (H2S), stored at 4 °C for 3 h, and then transplanted. Flaps were monitored until clinical rejection without immunosuppression. In the MATCH group, flap survival did not significantly differ between the saline and hydrogen sulfide treatments (p = 0.483) but was reduced with the sodium iodide treatment (p = 0.007). In the MISMATCH group, survival was similar between the saline and hydrogen sulfide treatments (p = 0.483) but decreased with the sodium iodide treatment (p = 0.007). Rhabdomyolysis markers showed lower but non-significant levels in the experimental subgroups for both the MATCH and MISMATCH animals. This study provides insightful data for the field of antioxidant-based approaches in VCA and transplantation.

24 Hours Ex-vivo Hypothermic Acellular Perfusion of Porcine Forelimb: A 7-day Follow-up Study.

One of the limiting factors for vascularized composite allograft (VCA) storage is the short viable ischemic time (4-6 hours). Hypothermic machine perfusion (MP) enables near-physiological preservation, avoiding the deleterious effects of hypoxia and static cooling. This study aims to compare muscle injury after 24-hour acellular perfusion with static cold storage (SCS) in a porcine limb replantation model, examining outcomes for up to 7 days after reperfusion. Sixteen procured porcine forelimbs were perfused hypothermic for 24 hours with Histidine-Tryptophan-Ketoglutarate (HTK, n=8) or preserved on ice for 4 hours (SCS, n=8) before orthotopic replantation. Muscle injury was assessed using biochemical markers and muscle biopsies were analyzed using the Histologic Injury Severity Score (HISS). During preservation, limb weight decreased by 2% in the SCS group and increased by 44% in the perfusion group (p<0.001). Twelve limbs (HTK, n=6; SCS, n=6) survived for 7 days. Three days after replantation, increased creatinine kinase levels were observed in the perfusion group (33781 mmol/liter versus 2163 mmol/liter; p<0.001). Mean endpoint HISS was 3.8 (SD 0.7) in the perfusion group and 1.8 (SD 0.7) in the SCS group (p=0.008), mostly due to increased edema (p=0.004). 24 hours of hypothermic MP and 4 hours of SCS of VCA demonstrated both minimal degenerated muscle tissue seven days after replantation.

Topical Tacrolimus and Mycophenolic Acid Therapy Synergizes with Low Dose Systemic Immunosuppression to Sustain Vascularized Composite Allograft Survival

AimThe goal of this study was to evaluate whether topical administration of tacrolimus (TAC) and mycophenolic acid (MPA) at the transplant site enables vascularized composite allograft (VCA) survival with significant minimization of the dose and adverse effects of systemic TAC (STAC) immunosuppression. Materials and methodsLewis (Lew) rats received orthotopic hind limb allotransplants from fully mismatched Brown Norway (BN) donors. Group 1 (Controls) received no treatment. Other groups were treated with STAC at a dose of 1 mg/kg/day for 7 days. On post-operative day (POD) 8, the STAC dose was dropped to 0.1 mg/kg/day for Group 2 and maintained at 1 mg/kg for Group 3. Group 4 received topical application of TAC and MPA on the transplanted (Tx) limb starting POD 8 without STAC. Group 5 received topical TAC and MPA on the contralateral non-Tx limb and Group 6 received topical TAC and MPA on the Tx limb starting POD 8 along with low dose STAC (0.1 mg/kg/day). Treatment was continued until the study end point was reached, defined as either grade 3 rejection or allograft survival exceeding 100 days. .We conducted sequential LC-MS/MS measurements to assess TAC and MPA concentrations in both blood/plasma and allograft tissues. Additionally, we evaluated markers indicative of organ toxicity associated with STAC immunosuppression. ResultsCompared to controls, topical therapy with TAC+MPA significantly prolonged allograft survival beyond 100 daysat very low dose STAC (0.1 mg/kg/day) (Group 6). The histopathological assessment of the grafts was consistent with the clinical outcomes. .Drug levels in blood/plasma remained low or undetectable, while allograft tissues showed higher drug concentrations compared to contralateral limb tissues (P<0.05). . Urinary creatinine clearance remained within the normal range at 2.5 mL/min. ConclusionCombination therapy with topical TAC and MPA synergizes with a very low dose, corticosteroid- free-STAC regimen and facilitates rejection-free, prolonged VCA survival without morbidity.

Normothermic Ex Situ Machine Perfusion of Vascularized Composite Allografts with Oxygen Microcarriers for 12 Hours Using Real-Time Mitochondrial Redox Quantification.

Normothermic ex situ perfusion of vascularized composite allografts (VCAs) necessitates high oxygen demand and, thus, increased metabolic activity, which, in turn, requires the use of blood-based perfusion solutions. However, blood-derived perfusates, in turn, constitute an antigenic load. To circumvent this immunogenic problem, we used a perfusate enriched with acellular dextrane oxygen microcarriers to perfuse rat hindlimbs. Rat hindlimbs (n = 11) were perfused with either (non-), oxygenated dextrane-enriched Phoxilium, or Phoxilium enriched with dextrane oxygen microcarriers (MO2) for 12 h at 37 °C or stored on ice. Oxygenation of the skeletal muscle was assessed with Raman spectroscopy, tissue pO2-probes, and analysis of the perfusate. Transmission electronic microscopy was utilized to assess the ultrastructure of mitochondria of the skeletal muscle. For all evaluated conditions, ischemia time until perfusion was comparable (22.91 ± 1.64 min; p = 0.1559). After 12 h, limb weight increased significantly by at least 81%, up to 124% in the perfusion groups, and by 27% in the static cold storage (SCS) group. Raman spectroscopy signals of skeletal muscle did not differ substantially among the groups during either perfusion or static cold storage across the duration of the experiment. While the total number of skeletal muscle mitochondria decreased significantly compared to baseline, mitochondrial diameter increased in the perfusion groups and the static cold storage group. The use of oxygen microcarriers in ex situ perfusion of VCA with acellular perfusates under normothermic conditions for 12 h facilitates the maintenance of mitochondrial structure, as well as a subsequent recovery of mitochondrial redox status over time, while markers of muscle injury were lower compared to conventional oxygenated acellular perfusates.

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

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. 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. 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.

Robotic Bladder Autotransplantation: Preclinical Studies in Preparation for First-in-human Bladder Transplant.

Human urinary bladder transplantation has never been performed. From a technical standpoint, challenges include the complex deep pelvic vascular anatomy, limited intraoperative visualization, and high procedural complexity. In preparation for a first-in-human clinical trial, we report preclinical studies to develop the technique of robotic retrieval and autotransplantation of vascularized composite bladder allograft. Institutional Animal Care and Use Committee, Institutional Review Board, and UNOS (United Network for Organ Sharing) approvals were obtained, and IDEAL (Idea, Development, Exploration, Assessment, Long-term Study) Reporting Guidelines were followed. Robotic vascularized composite bladder allograft recovery, back-table graft preparation, and robotic autotransplantation were performed in 3 vascularized model settings: living porcine (n=3), pulsatile human cadavers (n=2), and heart-beating brain-dead deceased research human donors (n=5). Our primary objective was to develop a reproducible technique for robotic vascularized composite bladder allograft transplantation. Technical success was defined by adequate, sustained vascularized composite bladder allograft reperfusion. Secondary objectives were intraoperative parameters, including operative time, graft ischemia time, and blood loss. Successful robotic vascularized composite bladder allograft autotransplantation was achieved in 2 porcine, 1 cadaver, and 3 brain-dead research donors. In the heart-beating research donors, console time decreased with successive surgeries, and visual inspection revealed healthy revascularized autografts with prompt, global indocyanine green immunofluorescence uptake. In 1 heart-beating donor who was hemodynamically maintained for 12 hours postoperatively, reinspection confirmed excellent maintained global vascularized composite bladder allograft vascularity and bladder mucosal integrity. To our knowledge, the first preclinical experience of bladder autotransplantation in vascularized models is reported, including robotic vascularized composite bladder allograft recovery, back-table reconstruction, and autotransplantation. This experience represents the essential preclinical work required to build toward the first-in-human trial of bladder transplantation, performed under a UNOS-approved genitourinary vascularized composite bladder allograft program (NCT No. 05462561).

2023 TERMIS – AMERICAS Conference &amp; Exhibition Boston Marriott Copley Place April 11–14, 2023

2023 TERMIS – AMERICAS Conference &amp; Exhibition Boston Marriott Copley Place April 11–14, 2023

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.

Tolerance Induction in Vascularized Composite Allotransplantation-A Brief Review of Preclinical Models.

Pre-clinical studies are an obligatory tool to develop and translate novel therapeutic strategies into clinical practice. Acute and chronic rejection mediated by the recipient's immune system remains an important limiting factor for the (long-term) survival of vascularized composite allografts (VCA). Furthermore, high intensity immunosuppressive (IS) protocols are needed to mitigate the immediate and long-term effects of rejection. These IS regiments can have significant side-effects such as predisposing transplant recipients to infections, organ dysfunction and malignancies. To overcome these problems, tolerance induction has been proposed as one strategy to reduce the intensity of IS protocols and to thereby mitigate long-term effects of allograft rejection. In this review article, we provide an overview about animal models and strategies that have been used to induce tolerance. The induction of donor-specific tolerance was achieved in preclinical animal models and clinical translation may help improve short and long-term outcomes in VCAs in the future.

OPTN/SRTR 2021 Annual Data Report: Vascularized Composite Allograft

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

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.

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.

Cortical reintegration after facial allotransplantation.

Neural plasticity of the brain or its ability to reorganize following injury has likely coincided with the successful clinical correction of severe deformity by facial transplantation since 2005. In this study, we present the cortical reintegration outcomes following syngeneic hemifacial vascularized composite allograft (VCA) in a small animal model. Specifically, changes in the topographic organization and unit response properties of the rodent whisker-barrel somatosensory system were assessed following hemifacial VCA. Clear differences emerged in the barrel-cortex system when comparing naïve and hemiface transplanted animals. Neurons in the somatosensory cortex of transplanted rats had decreased sensitivity albeit increased directional sensitivity compared with naïve rats and evoked responses in transplanted animals were more temporally dispersed. In addition, receptive fields were often topographically mismatched with the indication that the mismatched topography reorganized within adjacent barrel (same row-arc bias following hemifacial transplant). These results suggest subcortical changes in the thalamus and/or brainstem play a role in hemifacial transplantation cortical plasticity and demonstrate the discrete and robust data that can be derived from this clinically relevant small animal VCA model for use in optimizing postsurgical outcomes.NEW & NOTEWORTHY Robust rodent hemifacial transplant model was used to record functional changes in somatosensory cortex after transplantation. Neurons in the somatosensory cortex of face transplant recipients had decreased sensitivity to stimulation of whiskers with increased directional sensitivity vs. naive rats. Transplant recipient cortical unit response was more dispersed in temporary vs. naive rats. Despite histological similarities to naive cortices, transplant recipient cortices had a mix of topographically appropriate and inappropriate whiskered at barrel cortex relationships.

Validating a Novel Device to Improve Skin Color Matching for Face Transplants.

A prospective study of 100 individuals was conducted. All participants were photographed and scanned with the Nix Color Sensor. Sixty pairwise comparisons were randomly generated. Skin color analysis was performed using photographs and the Nix Color Sensor. Delta E2000 values were compared to mean evaluator ratings using a Spearman correlation analysis. One hundred patients were included. A Spearman's correlation demonstrated a strong inverse correlation between Delta E2000 values and the mean evaluator ratings. The higher the mean evaluator rating for likeness, the lower the delta. A correlation coefficient of -0.850 demonstrates a statistically significant relationship (P < 0.01). When the Delta E2000 rises above 5 there is a significant drop in the mean evaluator ratings. As mean evaluator ratings of 5 and above would be considered adequate for face transplant amongst most plastic surgeons, an E2000 value of 5 or lower should be targeted when matching donors with recipients for face transplant. The Nix Color Sensor positively correlates to the plastic surgeon's perception of skin color and can serve as an adjunct in donor selection for facial VCAs.

Exceeding the Limits of Static Cold Storage in Limb Transplantation Using Subnormothermic Machine Perfusion.

For 50 years, static cold storage (SCS) has been the gold standard for solid organ preservation in transplantation. Although logistically convenient, this preservation method presents important constraints in terms of duration and cold ischemia-induced lesions. We aimed to develop a machine perfusion (MP) protocol for recovery of vascularized composite allografts (VCA) after static cold preservation and determine its effects in a rat limb transplantation model. Partial hindlimbs were procured from Lewis rats and subjected to SCS in Histidine-Tryptophan-Ketoglutarate solution for 0, 12, 18, 24, and 48 hours. They were then either transplanted (Txp), subjected to subnormothermic machine perfusion (SNMP) for 3 hours with a modified Steen solution, or to SNMP + Txp. Perfusion parameters were assessed for blood gas and electrolytes measurement, and flow rate and arterial pressures were monitored continuously. Histology was assessed at the end of perfusion. For select SCS durations, graft survival and clinical outcomes after transplantation were compared between groups at 21 days. Transplantation of limbs preserved for 0, 12, 18, and 24-hour SCS resulted in similar survival rates at postoperative day 21. Grafts cold-stored for 48 hours presented delayed graft failure (p = 0.0032). SNMP of limbs after 12-hour SCS recovered the vascular resistance, potassium, and lactate levels to values similar to limbs that were not subjected to SCS. However, 18-hour SCS grafts developed significant edema during SNMP recovery. Transplantation of grafts that had undergone a mixed preservation method (12-hour SCS + SNMP + Txp) resulted in better clinical outcomes based on skin clinical scores at day 21 post-transplantation when compared to the SCS + Txp group (p = 0.01613). To date, VCA MP is still limited to animal models and no protocols are yet developed for graft recovery. Our study suggests that ex vivo SNMP could help increase the preservation duration and limit cold ischemia-induced injury in VCA transplantation.

Video Messaging to Increase Vascularized Composite Allograft Donation Willingness in United States Military Veterans.

Background.Expansion of vascularized composite allograft (VCA) transplantation depends on the public’s willingness to donate VCA organs, including face, extremities, and genitourinary organs. This study evaluated the effectiveness of video messaging on VCA donation willingness in US military veterans, a key stakeholder in VCA transplantation.Methods.Participants (n = 556) were randomized to 1 of 3 VCA video messaging interventions (informational, testimonial, or blended), a general (non-VCA) organ donation video message, or a control (nondonation) video message. Questionnaires were completed at pre- and postintervention and at 3-wk follow-up.Results.Veterans exposed to any VCA video messaging were more likely to express VCA donation willingness (69%, n = 203/296) than those exposed to general donation messaging (53%, n = 47 of 89; P = 0.006) or No Donation Messaging (37%, n = 36 of 97; P < 0.001). A significantly higher proportion of participants who received Blended VCA Messaging were willing to be VCA donors, compared with the Informational VCA Messaging group (79% versus 61%, P = 0.006). Each VCA messaging video resulted in a significant pre- to postintervention increase in the proportion of participants willing to donate their own face, hands, and legs (P < 0.03).Conclusions.Brief educational videos focused on VCA transplantation can have a demonstrable and verifiable impact on rates of VCA donation willingness in veterans.

427.3: Military Veterans’ Knowledge, Attitudes, and Interest in VCA Treatment for Disfiguring Service-Related Injuries

Background: Thousands of American service members have suffered catastrophic injuries to the head, face, and extremities resulting in functional limitations and significant disfigurement. The rise of vascularized composite allograft (VCA) procedures now allows for hand and face transplants, which can improve the functioning, mobility, and quality of life for these veterans, particularly those who have not responded well to available reconstructive procedures or prosthetics. Despite potentially life-enhancing outcomes, however, the awareness of and interest in this treatment option by VCA-eligible veterans is unknown. By examining this population’s receptivity to VCA, the study’s goal of identifying the assets and barriers to receiving a VCA will instruct more informed decision making about this treatment. Methods: In collaboration with the Veterans Affairs Medical Center (VAMC) in Coatesville, PA, and the Department of Defense Joint Trauma Registry, over 1,100 medical records from 2010-2019 were reviewed for applicable ICD-9 codes. In-depth semi-structured interviews were conducted via telephone or video conference with up to 60 military veterans to examine current health status, treatments and therapies, impact of their injuries on daily life, and reactions to VCA, as the primary domains of inquiry. Interviews were audio-recorded for accuracy, deidentified, and transcribed for analysis. The existing domains and emergent themes formed the basis of a codebook, and MAXQDA software was used to facilitate qualitative coding of the data. Results: Most participants interviewed to date, reported amputation of one or both hands. Although largely unfamiliar with the technical terminology of “Vascularized Composite Allotransplantation,” most expressed familiarity with the procedure when described in more detail. While initial reactions were largely positive, many participants did not see this treatment as necessary for themselves. Multiple participants indicated greater receptivity if they were less adapted to their injury or did not have at least one functioning upper limb. Reported concerns included possible graft rejection, recovery time, medical fatigue, side effects of immunosuppression, and the effectiveness of the VCA procedure. Respondents identified more functional independence as the most critical and desired outcome of receiving a VCA graft in addition to navigating their day-to-day environments with fewer accommodations and adaptive equipment. Conclusion: Participants viewed VCA as an interesting medical advancement and acknowledged its potential benefits but also expressed skepticism about its efficacy. These observations provide a knowledge base for researchers and practitioners engaged in growing the field of VCA. Further examination of the attitudes and experiences of the caregivers and healthcare providers of VCA-eligible patients would offer valuable perspectives in informing decision making about VCA. U.S. Department of Defense, Grant/Award Number: W81XWH-19-1-0274.