Faculty Bibliography

BACKGROUND/UNASSIGNED:A deeper understanding of acute rejection in vascularized composite allotransplantation is paramount for expanding its utility and longevity. There remains a need to develop more precise and accurate tools for diagnosis and prognosis of these allografts, as well as alternatives to traditional immunosuppressive regimens. METHODS/UNASSIGNED:Twenty-seven skin biopsies collected from 3 vascularized composite allotransplantation recipients, consisting of face and hand transplants, were evaluated by histology, immunohistochemistry staining, and gene expression profiling. RESULTS/UNASSIGNED:significantly predicted inflammation specific to vascularized composite allografts that required therapeutic intervention. CONCLUSIONS/UNASSIGNED:The mechanism of vascularized composite allograft-specific inflammation and rejection appears to be conserved across different patients and skin on different anatomical sites. A concise gene signature can be utilized to ascertain graft status along with a continuous scale, providing valuable diagnostic and prognostic information to supplement current gold standards of graft evaluation.

As more data becomes available, the Banff 2007 working classification of skin-containing vascularized composite allograft (VCA) pathology is expected to evolve and develop. This report represents the Banff VCA Working Group's consensus on the first revision of the 2007 scoring system. Prior to the 2022 Banff-CST Joint Meeting, eighty-three clinicians and/or researchers were invited to a virtual meeting to discuss whether the 2007 Banff VCA system called for a revision. Unanimously, it was determined that the vascular changes were to be included in the first revision. Subsequently, two international online surveys, each followed by virtual discussions, were launched. The goals were: 1) to identify which changes define severe rejection, 2) to grade their importance in the evaluation of severe rejection, 3) to identify emerging criteria to diagnose rejection. A final hybrid (in person and virtual) discussion at the Banff/CST join meeting finalized the terminology, the definition, a scoring system, and a reporting system of the vascular changes. This proposal represents an international consensus on this topic and establishes the first revision of the Banff 2007 working classification of skin-containing vascularized composite allograft pathology.

BACKGROUND:As the obesity crisis in the United States continues, some renal transplantation centers have liberalized their BMI criteria necessary for transplant eligibility. More individuals with larger body-habitus related comorbidities with End-Stage Renal Disease (ESRD) now qualify for renal transplantation (RT). Surgical modalities from other fields also interact with this patient population. METHODS:In order to assess surgical outcomes of panniculectomy in the context of renal transplantation and ESRD, the authors performed a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guidelines. Due to a paucity of existing primary studies, we retrospectively collected data on patients with ESRD undergoing panniculectomy from the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP) to evaluate outcomes of body contouring in this patient population. RESULTS:From the systematic review, a total of 783 ESRD patients underwent panniculectomy among the studies identified. Of these, 91 patients underwent panniculectomy simultaneously to RT while 692 had their pannus resected prior to kidney transplant. The most common complication was hematoma followed by wound dehiscence. From the NSQIP database, 24 868 patients met the inclusion criteria for analysis. In the setting of renal transplant status, patients with diabetes, hypertension requiring medication, and requiring dialysis were more likely to suffer postoperative complications (OR 1.31, 1.15, and 2.2, respectively). However, upon sub-analysis of specific types of complications, the only retained association was between diabetes and wound complication. CONCLUSION/CONCLUSIONS:Preliminary data show that panniculectomy in ESRD patients appears to be safe, though with a nominal increased risk for complications. Pannus resection does not appear to impact post-transplantation outcomes, including long-term allograft survival. Larger, higher powered, randomized studies are needed to confirm the safety, utility, and medical benefit of panniculectomy in the context of renal transplantation.

OBJECTIVE:Rejection is common and pernicious following Vascularized Composite Allotransplantation (VCA). Current monitoring and diagnostic modalities include the clinical exam which is subjective and biopsy with dermatohistopathologic Banff grading, which is subjective and invasive. We reviewed literature exploring non- and minimally invasive modalities for diagnosing and monitoring rejection (NIMMs) in VCA. METHODS:PubMed, Cochrane, and Embase databases were queried, 3125 unique articles were reviewed, yielding 26 included studies exploring 17 distinct NIMMs. Broadly, NIMMs involved Imaging, Liquid Biomarkers, Epidermal Sampling, Clinical Grading Scales, and Introduction of Additional Donor Tissue. RESULTS:Serum biomarkers including MMP3 and donor-derived microparticles rose with rejection onset. Epidermal sampling non-invasively enabled measurement of cytokine & gene expression profiles implicated in rejection. Both hold promise for monitoring. Clinical grading scales were useful diagnostically as was reflection confocal microscopy. Introducing additional donor tissue showed promise for preemptively identifying rejection but requires additional allograft tissue burden for the recipient. CONCLUSION/CONCLUSIONS:NIMMs have the potential to dramatically improve monitoring and diagnosis in VCA. Many modalities show promise however, additional research is needed and a multimodal algorithmic approach should be explored.

Over the past year, three scientific teams conducted experiments of genetically-edited porcine organs into human recipients, three of whom were deceased and one living. In this editorial, we describe challenges for the design of initial xenotransplantation clinical trials and focus on patient selection, consent, and requisite post-transplant follow-up. Given the uncertain clinical benefit of xenotransplantation, we propose that patient selection criteria might include novel elements such as approaching patients who have low quality of life and strong aversion to continued dialysis therapy. We set expectations related to the importance of informing and protecting family members and medical teams who could be exposed to zoonotic viral infection from the donor organ and/or receive unwanted publicity. Meeting these challenges in trial design and oversight will require multidisciplinary expertise, a conceptual model that extends beyond the individual patient, and creative collaboration between scientists and regulatory agencies.

OBJECTIVE:Transplant renal artery stenosis (TRAS) after renal transplantation is a common cause of graft dysfunction and failure. Endovascular intervention in the form of percutaneous transluminal angioplasty (PTA) and stenting has rapidly become the dominant treatment modality for the TRAS. There is a paucity of clinical data on use of drug-eluting stent (DES) for TRAS. We investigated the outcomes of patients with clinically significant TRAS undergoing DES placement. METHODS:A retrospective review of patients with clinically significant TRAS undergoing PTA with DES placement from June 2014 to April 2021 was conducted. Patients treated for TRAS exhibited uncontrolled hypertension and/or unexplained allograft dysfunction. Patient demographics, procedural details, and follow-up outcomes were collected. Primary endpoints were the in-stent primary patency and graft survival. Secondary endpoints were freedom from reintervention, primary-assisted patency and access-related complications. RESULTS:Thirteen TRAS in twelve patients with graft function alteration were treated with DES. The median age was 57 years (interquartile range (IQR), 48-63 years), and nine (70%) patients were male (Table). The median follow-up was 9 months (IQR, 4-52 months). The most common comorbidity was hypertension (100%), coronary artery disease (83%) and diabetes. The median time from deceased donor transplant to intervention was 5.8 months (IQR, 3.5-6.7 months). TRAS was most commonly found at the juxta-ostial segment (77%). The procedure was performed with carbon dioxide angiography with minimal amount of iodinated contrast (median, 3 mL) under local anesthesia in nine (69%) and general anesthesia in four (31%) patients. The median stent diameter was 4.5 mm (IQR, 4-5 mm), and the median stent length was 15 mm (IQR, 15-18 mm). No intraoperative complications occurred. The rates of stenosis-free primary patency of the DES and graft survival were 76% and 100%, respectively. All three reinterventions for restenosis resulted from the kinking of the transplant renal artery proximal to the DES, which were treated by extending the stent more proximally 1-2 mm into the external iliac artery. There were no access-related complications. The median time to reintervention was 0.9 months (range, 0.23-2 months). Freedom from reintervention and primary-assisted patency were 76% and 100%, respectively. CONCLUSIONS:Our study demonstrates that DES is a safe and effective treatment modality in patients with TRAS at short to mid-term follow-up. As all reinterventions after DES were performed due to kinking of the transplant renal artery proximal to the stent, bridging of the DES 1-2 mm into the external iliac artery is recommended.

BACKGROUND:There is a paucity of data on the impact of cytomegalovirus (CMV) serostatus and CMV infection on outcomes in facial vascularized composite allotransplantation. METHODS:This international, multicenter, retrospective cohort study presents data on CMV and basic transplant-related demographics, including pretransplant viral D/R serostatus, and duration of antiviral prophylaxis. CMV-related complications (viremia, disease), allograft-related complications (rejection episodes, loss), and mortality were analyzed. RESULTS:We included 19 patients, 4 of whom received CMV high-risk transplants (D+/R-). CMV viremia was noted in 6 patients (all 4 D+/R- patients and 2 D-/R+), mostly within the first-year posttransplant, shortly after discontinuation of antiviral prophylaxis (median 2 mo). CMV disease occurred in 2 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 mo). CONCLUSIONS:D+/R- patients were 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 because of CMV or rejection. Thus, CMV D+/R- face transplantation can likely be safely performed with prophylaxis, active surveillance, and prompt treatment.

BACKGROUND:Acute rejection (AR) is a common complication in facial transplant (FT) patients associated with allograft edema and erythema. Our study aims to demonstrate the feasibility of using software-based 3-dimensional (3D) facial analysis to quantify edema as it resolves during/after AR treatment in an FT patient. METHODS:Our patient is a 23-year-old man who underwent a face and bilateral hand allotransplant in August 2020. The Vectra H1 (Canfield, Fairfield, NJ) portable scanner was used to capture 3D facial images at 8 time points between postoperative day (POD) 392 and 539. The images were analyzed with the Vectra Software using a rejection-free image (POD 539) as a control. RESULTS:Edema increased in the periorbital, lower third, and submandibular regions before AR treatment (POD 392-415). At POD 448, total facial edema was reduced to near baseline values in response to plasmapheresis and thymoglobulin (+156.94 to +28.2 mL). The fastest and most notable response to treatment was seen in the periorbital region, while some edema remained in the submandibular (+19.79 mL) and right lower third (+8.65 mL) regions. On POD 465, after the initial improvement, the edema increased but was resolved with steroid use. Facial edema did not correlate with the histopathological evaluation in our patient. CONCLUSIONS:We demonstrated the feasibility of analyzing 3D facial images to quantify edema during/after AR treatment in an FT patient. Our analysis detected edema changes consistent with AR followed by an improvement after treatment. This technology shows promise for noninvasive monitoring of FT patients.

Although the ethical and technical feasibility of face transplant (FT) has been established, current literature lacks consensus on functional outcomes monitoring for recipients. This systematic review aims to appraise and summarize the current literature on tools used to assess motor functional outcomes in FT. This study complied with the guidelines outlined in the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). On September 15, 2020, two reviewers conducted independent electronic searches using medical literature databases, without language or time frame limitations. Eligibility criteria included studies reporting on the evaluation of motor functional outcomes in face transplant recipients. Of 451 papers found in the literature, 12 fulfilled the study inclusion criteria. The reported tools included clinical scales/examinations, electromyography, optical movement tracking devices, muscle volumetric measurement using magnetic resonance imaging, and software-based video and photo analyses. The frequency of data collection varied from every three months to every year. Publications reporting on motor functional outcomes tracking tools vary broadly and demonstrate a lack of consensus. Although quantitative measurements are desirable, adapted clinical scales are still the current standard of care.