Molecular Signature Associated With Acute Rejection in Vascularized Composite Allotransplantation.

Background: 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: 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: Biopsies with clinical signs and symptoms of rejection, irrespective of histopathological grading, were significantly enriched for genes contributing to the adaptive immune response, innate immune response, and lymphocyte activation. Inflammation episodes exhibited significant fold change correlations between the face and hands, as well as across patients. Immune checkpoint genes were upregulated during periods of inflammation that necessitated treatment. A gene signature consisting of CCL5, CD8A, KLRK1, and IFNγ significantly predicted inflammation specific to vascularized composite allografts that required therapeutic intervention. Conclusions: 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.

Combined Whole Eye and Face Transplant: Microsurgical Strategy and 1-Year Clinical Course.

Importance: Catastrophic facial injury with globe loss remains a formidable clinical problem with no previous reports of reconstruction by whole eye or combined whole eye and facial transplant. Objective: To develop a microsurgical strategy for combined whole eye and facial transplant and describe the clinical findings during the first year following transplant. Design, Setting, and Participant: A 46-year-old man who sustained a high-voltage electrical injury with catastrophic tissue loss to his face and left globe underwent combined whole eye and face transplant using personalized surgical devices and a novel microsurgical strategy at a specialized center for vascularized composite allotransplantation. Main Outcomes and Measures: Reperfusion and viability of the whole eye and facial allografts, retinal function, and incidence of acute rejection. Results: The patient underwent a combined whole eye and face transplant from an immunologically compatible donor with primary optic nerve coaptation and conventional postoperative immunosuppression. Globe and retinal perfusion were maintained throughout the immediate postoperative period, evidenced by fluorescein angiography. Optical coherence tomography demonstrated atrophy of inner retinal layers and attenuation and disruption of the ellipsoid zone. Serial electroretinography confirmed retinal responses to light in the transplanted eye. Using structural and functional magnetic resonance imaging, the integrity of the transplanted visual pathways and potential occipital cortical response to light stimulation of the transplanted eye was demonstrated. At 1 year post transplant (postoperative day 366), there was no perception of light in the transplanted eye. Conclusions and Relevance: This is the first report of whole eye transplant combined with facial transplant, demonstrating allograft survival including rejection-free graft survival and electroretinographic measurements indicating retinal response to light stimuli. These data highlight the potential for clinical allotransplantation for globe loss.

From Selfies to Surgery: Unveiling Trends and Ethical Considerations in Facial Feminization on Instagram.

Facial feminization surgery (FFS) is a critical gender-affirming intervention utilized to alleviate gender dysphoria. This study investigates the role of Instagram in shaping public perceptions and disseminating information about FFS. The authors analyzed the most recent 500 Instagram posts using the hashtag "#facialfeminizationsurgery" through a nonbiased data scraping platform between June 1, 2023 and October 13, 2023. Posts were categorized, for example, by tone, author, hospital, practice location, and whether it was a patient or physician-reported outcome. Of the posts, 85% connoted a positive tone. Health care providers and organizations posted 65.4% of content. Geographic breakdown showed that of posts written in English, 55% of health care providers were from the United States. The top 3 most frequently cited locations outside of the United States were India (25.2%), England (19.1%), and South Korea (16.0%). Common themes among posts were perception of FFS and whether it be deemed cosmetic or reconstructive, ethical considerations, and insurance/funding. 36% of posts were advertisements, and 20% were educational, which emphasized the role of social media in disseminating information. This study emphasizes the dynamic nature of social media and its large impact on FFS with regard to disseminating accurate information, navigating the patient-physician relationship, and posting ethical content. The demographics of the users and posts show growing global interest in FFS, a largely positive tone from users, and a large presence of health care workers. Lastly, Instagram is an educational tool for FFS and spreads awareness of insurance and issues faced by patients through first-hand perspectives.

Computerized Surgical Planning in Face Transplantation.

Face transplantation (FT) has emerged as a critical intervention for patients with complex facial deformities unsuitable for conventional reconstructive methods. It aims to restore essential functions such as facial expression, mastication, and speech, while also improving psychosocial health. The procedure utilizes various surgical principles, addressing unique challenges of craniofacial complexity and diverse injury patterns. The integration of Computerized Surgical Planning (CSP) leverages computer-aided technologies to enhance preoperative strategy, intraoperative navigation, and postoperative assessment. CSP utilizes three-dimensional computed tomography, printing, angiography, and navigation systems, enabling surgeons to anticipate challenges and reduce intraoperative trial and error. Through four clinical cases, including a groundbreaking combined face and bilateral hand transplant, CSP's role in FT is highlighted by its ability to streamline operative processes and minimize surgical revisions. The adoption of CSP has led to fewer cadaveric rehearsals, heightened operative precision, and greater alignment with preoperative plans. Despite CSP's advancements, it remains complementary to, rather than a replacement for, clinical expertise. The demand for technological resources and multidisciplinary teamwork is high, but the improved surgical outcomes and patient quality of life affirm CSP's value in FT. The technology has become a staple in reconstructive surgery, signaling a step forward in the evolution of complex surgical interventions.

Novel Osteomyocutaneous Flap Model for Vascularized Composite Allotransplantation.

Background: Vascularized composite allotransplantation (VCA) has become a viable option for restoration of devastating injuries that are not amenable to conventional reconstructive techniques. However, the relative scarcity of procedures performed worldwide, as well as the potential for iatrogenic injury with biopsies, makes studying the immunopathogenesis of acute rejection challenging. Translational VCA research focuses on developing strategies to overcome these barriers with the use of animal models can be technically challenging and difficult to replicate without highly trained microsurgeons. Methods: We describe a modified model of a femur-based composite tissue allograft using an adapted vascular cuff anastomotic technique with a tunneled skin flap in a rodent model. Results: The use of a heterotopic osteomyocutaneous flap with a subcutaneously tunneled-skin paddle to the posterolateral aspect of the recipient rodent allows for ease of flap monitoring and reduces the risk of self-mutilation. A total of six transplantations were conducted with no signs of self-mutilation. Operative time decreased as our surgical technique improved, and long-term graft tolerance was possible under our immunosuppressive regimen. Additionally, we demonstrate cases of successful transplantation in both an allogeneic and syngeneic rodent model. Conclusion: Animal models, although technically challenging, are a reliable and reproducible modality that has been used to investigate various aspects of VCA immunology. We describe the success of an osteomyocutaneous flap with a modified vascular cuff anastomosis that can be used by investigators with less experience in microsurgical techniques to further our understanding of VCA physiology. Furthermore, tunneling of the skin paddle reduces the risk of self-mutilation and other external factors affecting the graft.

Technical Pearls and Pitfalls of Facial Feminization Surgery: A Review of Techniques From a Single Institutional Practice.

BACKGROUND: Facial feminization surgery (FFS) is an emerging practice that falls under the broader umbrella of gender-affirming surgery. Various approaches exist to feminize the face, yet few published articles describe in detail the techniques of each component procedure. Considering the diversity of interventions employed, the objective of this manuscript is to highlight FFS techniques utilized by the senior author and create a corresponding media gallery. METHODS: All patients with the diagnosis of gender dysphoria that were referred to the senior author for FFS consultation between June 2017 and August 2022 were reviewed. Data were retrospectively collected from electronic medical records according to the institutional review board (IRB)-approved study protocol. Data collected and analyzed included demographics, operative documentation, and postoperative follow-up. Multimedia material was collected intraoperatively and postoperatively. RESULTS: A total of 231 patients underwent 262 operations with a total of 1224 FFS procedures. The average follow-up time was 7.7 ± 11 months. Out of the 262 operations, 24 (9.2%) patients experienced minor complications, including 3 (1.1%) with wound dehiscence, 13 (5.0%) with hematomas, and 14 (5.3%) with postoperative infection requiring antibiotics. Of those, 3 (1.1%) required a return to the operating room for washout or removal of malar implants. CONCLUSION: Although there is a consensus on the fundamental surgical principles to achieve adequate feminization of the facial architecture, the specific techniques to do so differ according to individual practices. As techniques diverge, so do their risk profiles and outcomes; techniques must, thus, align with patients' interventional goals. The material presented here is one of many that can support trainees and junior surgeons as they build a gender-affirming practice.

Incorporating Trauma-informed Approaches to Care in Vascularized Composite Allotransplantation.

Since 1998, vascularized composite allotransplantation (VCA) has been a growing area of research in the field of reconstructive surgery. Although conditions treated with VCA often result from a traumatic injury, there has been limited emphasis on incorporating trauma-informed care (TIC) models in VCA. Considering the importance of psychosocial well-being in VCA candidates and recipients, applying best practices in TIC to the face, upper extremity, and penile transplantation may be critical in minimizing retraumatization throughout the perioperative process. There are six main principles of TIC: safety; trustworthiness and transparency; peer support; collaboration and mutuality; empowerment and choice; and cultural, historical, and gender issues, which may be further incorporated in care for VCA patients. Evaluating for PTSD and incorporating TIC may have substantial benefit to postoperative outcomes.

First-in-Human Whole-Eye Transplantation: Ensuring an Ethical Approach to Surgical Innovation.

As innovations in the field of vascular composite allotransplantation (VCA) progress, whole-eye transplantation (WET) is poised to transition from non-human mammalian models to living human recipients. Present treatment options for vision loss are generally considered suboptimal, and attendant concerns ranging from aesthetics and prosthesis maintenance to social stigma may be mitigated by WET. Potential benefits to WET recipients may also include partial vision restoration, psychosocial benefits related to identity and social integration, improvements in physical comfort and function, and reduced surgical risk associated with a biologic eye compared to a prosthesis. Perioperative and postoperative risks of WET are expected to be comparable to those of facial transplantation (FT), and may be similarly mitigated by immunosuppressive protocols, adequate psychosocial support, and a thorough selection process for both the recipient and donor. To minimize the risks associated with immunosuppressive medications, the first attempts in human recipients will likely be performed in conjunction with a FT. If first-in-human attempts at combined FT-WET prove successful and the biologic eye survives, this opens the door for further advancement in the field of vision restoration by means of a viable surgical option. This analysis integrates recent innovations in WET research with the existing discourse on the ethics of surgical innovation and offers preliminary guidance to VCA programs considering undertaking WET in human recipients.

Meta-Analysis of Validated Quality of Life Outcomes Following Voice Feminization in Transwomen.

OBJECTIVES: For transwomen undergoing voice feminization interventions, fundamental frequency (F 0 ; vocal pitch) is a commonly reported functional outcome measure in the literature. However, F 0 may not correlate well with improvement in quality of life (QoL). Several validated voice-related QoL instruments have been used to assess QoL improvement in these patients, yet there is no consensus on the most appropriate instrument. This systematic review and meta-analysis aimed to assess the relationship between change in F 0 and QoL improvement following voice feminization, and to compare validated QoL instruments commonly used in this population. DATA SOURCES: PubMed, Cochrane, and Embase. REVIEW METHODS: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Primary studies of transwomen undergoing voice feminization, reporting validated QoL outcomes were included. Meta-analyses for associations between mean change in QoL score and mean change in F 0 , as well as variations in mean change in QoL score by QoL instrument, were performed using a multilevel mixed effects model. RESULTS: No statistically significant correlation was found between change in F 0 and QoL score improvement post-intervention. Different validated instruments showed statistically significant variation in QoL score change, with the Trans Women Voice Questionnaire (TWVQ) capturing a greater improvement in QoL score relative to other instruments. CONCLUSIONS: Lack of correlation between changes in F 0 and QoL improvement further supports that F 0 alone is insufficient to assess the efficacy of voice feminizing interventions. Validated QoL measures are useful adjuncts. Of these, the TWVQ appears to be the most sensitive for measurement of QoL improvement following voice feminization.

Facial Masculinization Surgery: An Analysis of Interest Trends Using Search Term Analysis.

INTRODUCTION: Facial masculinization surgery (FMS) is increasingly popular among cisgender and transgender men. The benefits of FMS are focused on facial identity and have been proven to decrease gender dysphoria in this population. Previous research showed increasing interest in gender affirmation surgery and facial feminization surgery, but the prevalence of FMS has not been explored. It is difficult to find these data based on surgical records alone because institutions do not have standardized methods of reporting and lack publications in the field. Our study aimed to analyze public interest in FMS by using worldwide Google Trends to quantify these trends. METHODS: A worldwide Google Trends search was completed from January 1, 2008, to December 31, 2022, for terms focused on FMS. Then, search terms were analyzed for nonfacial masculinization procedures and were aggregated. Lastly, a PubMed search was conducted for the terms "transgender" and "facial masculinization" from January 1, 2008, to December 31 st , 2022, to compare publication rates. RESULTS: Our data showed an increasing interest in FMS through Google search trends since the year 2008. A similar trend was demonstrated for non-FMS gender-affirming terms. PubMed analysis showed "transgender" medicine publishing rates were approximately 39.65 times greater than "facial masculinization" publishing rates, although "facial masculinization" medicine did produce a positive trend over the study period of approximately 4 publications per year. The medical literature on transgender surgeries rapidly outpaces publications specifically focusing on FMS. CONCLUSION: Our study showed increasing interest in gender affirmation surgery over time, particularly FMS. These increasing trends should encourage greater scientific exploration of FMS and research to properly quantify and assess surgical outcomes in this special population. Additional educational interventions for both the general public and medical providers, to increase awareness of unique challenges that impact this community and highlight changes in health care coverage over time, should be created to keep pace with increasing patient demand and address the physical, systemic, and psychosocial issues faced by people who identify as transgender.

Immunologic Outcomes in Cross-Sex Solid Organ Transplants: A Systematic Review and Meta-Analysis to Inform Vascularized Composite Allotransplantation.

BACKGROUND: Of nearly 90 hand and 50 face transplant recipients, only five have received a cross-sex vascularized composite allotransplantation (CS-VCA). CS-VCA has the potential to expand the donor pool and has been proven anatomically feasible and ethically acceptable in previous studies. However, there is a lack of immunologic data. This study evaluated the immunologic feasibility of CS-VCA through analysis of the solid organ transplant literature, given the paucity of CS-VCA data. The authors hypothesize that rates of acute rejection (AR) and graft survival (GS) in CS versus same-sex (SS) solid organ transplantation are similar. METHODS: A systematic review and meta-analysis were performed. Studies comparing GS or AR episodes in CS and SS adult kidney (KT) and liver transplant (LT) populations were included. Odds ratios were calculated for overall GS and AR for all SS and CS transplant combinations [male-to-female (MTF), female-to-male, and overall]. RESULTS: A total of 693 articles were initially identified with 25 included in the meta-analysis. No significant difference in GS was noted between SS-KT versus CS-KT [OR, 1.04 (95% CI, 1.00 to 1.07); P = 0.07), SS-KT versus MTF-KT [OR, 0.97 (95% CI, 0.90 to 1.04); P = 0.41), and SS-LT versus MTF-LT [OR, 0.95 (95% CI, 0.91 to 1.00); P = 0.05). No significant difference in AR was noted between SS-KT versus MTF-KT [OR, 0.99 (95% CI, 0.96 to 1.02); P = 0.57), SS-LT versus CS-LT [OR, 0.78 (95% CI, 0.53 to 1.16); P = 0.22], or SS-LT versus female-to-male LT [OR, 1.03 (95% CI, 0.95 to 1.12); P = 0.47]. For the remaining pairings, GS was significantly increased and AR was significantly decreased in the SS transplants. CONCLUSIONS: Published data suggest immunologic feasibility of CS-KT and CS-LT with the potential for generalization to the VCA population. CLINICAL RELEVANCE STATEMENT: In theory, CS-VCA could expand the potential donor pool, ultimately leading to decreased wait times for recipients and improve the likelihood of establishing a immunologically favorable donor-recipient match.

Gender-affirming hysterectomy in the United States: A comparative outcomes analysis and potential implications for uterine transplantation.

PURPOSE: Hysterectomy is a gynecological procedure sometimes performed as part of the gender-affirming process for transgender and gender-expansive patients assigned female at birth. Our goal was to compare surgical outcomes between patients undergoing gender-affirming hysterectomy and patients undergoing hysterectomy for benign menstrual disorders. We then explored the implications of gender-affirming hysterectomy for uterine transplantation. METHODS: We performed a retrospective cohort study using data from the American College of Surgeons National Surgical Quality Improvement Program database from 2009 through 2018. We identified patients undergoing hysterectomy in the United States based on Current Procedural Terminology code. We used the International Classification of Diseases 9 or 10 codes to identify patients with benign menstrual disorders (non-gender-affirming group) and gender dysphoria (gender-affirming group). We compared patient characteristics and surgical complications. RESULTS: Of the 40,742 patients that met inclusion criteria, 526 (1.3%) patients were individuals with gender dysphoria. Compared to patients who underwent hysterectomy for benign menstrual disorders, gender-affirming patients were younger, were healthier, had a lower prevalence of diabetes, and were more likely to undergo surgery in the outpatient setting, with shorter time to discharge. Complication rates were similar between groups. Logistic regression controlling for the American Society of Anesthesiology classification determined the difference of return to the operating room was not statistically significant (OR 1.082; 95% CI, 0.56-2.10; p = 0.816). CONCLUSION: Gender-affirming hysterectomy has a safety profile similar to hysterectomy performed for benign menstrual disorders. Researchers should further explore the possibility of uterus donation among these patients as they may be suitable candidates.

Combined Face and Whole Eye Transplantation: Cadaveric Rehearsals and Feasibility Assessment.

Background: In properly selected patients, combined face and whole eye transplantation (FWET) may offer a more optimal aesthetic and potentially functional outcome while avoiding the complications and stigma of enucleation and prosthetics. This study presents the most comprehensive cadaveric assessment for FWET to date, including rehearsal allograft procurement on a brain-dead donor. Methods: Over a 2-year period, 15 rehearsal dissections were performed on 21 cadavers and one brain-dead donor. After identification of a potential recipient, rehearsals assessed clinical feasibility and enabled operative planning, technical practice, refinement of personalized equipment, and improved communication among team members. Operative techniques are described. Results: Facial allograft procurement closely followed previously described face transplant techniques. Ophthalmic to superficial temporal (O-ST) vessel anastomosis for globe survival was assessed. Craniectomy allowed for maximal optic nerve and ophthalmic vessel pedicle length. Appropriate pedicle length and vessel caliber for O-ST anastomosis was seen. Research procurement demonstrated collateral blood flow to the orbit and surrounding structures from the external carotid system as well as confirmed the feasibility of timely O-ST anastomosis. Personalized cutting guides enabled highly accurate bony inset. Conclusions: This study formalizes an approach to FWET, which is feasible for clinical translation in judiciously selected patients. O-ST anastomosis seems to minimize retinal ischemia time and allow perfusion of the combined allograft on a single external carotid pedicle. Although restoration of vision likely remains out of reach, globe survival is possible.

Adrenal schwannoma can be FDG-Avid on PET/CT: case report and review of historic institutional pathology.

Schwannomas are benign, generally indolent tumors of neural crest origin and comprise the most common histologic tumor of peripheral nerves. Schwannomas are a rare histology for retroperitoneal tumors and very rare histologic findings for tumors of the adrenal gland with fewer than 50 cases in the reported literature. Here we present a case report of a non-hormonally functional but metabolically active adrenal tumor with indeterminate imaging characteristics with final pathology showing a 6.1 cm adrenal schwannoma as well as historical institutional pathology review revealing two additional cases.

Minimally and Non-invasive Approaches to Rejection Identification in Vascularized Composite Allotransplantation.

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: 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.

Vascularized Composite Allotransplantation of the Hand: A Systematic Review of Eligibility Criteria.

BACKGROUND: Hand transplantation (HT) has emerged as an intervention of last resort for those who endured amputation or irreparable loss of upper extremity function. However, because of the considerable effort required for allograft management and the risks of lifelong immunosuppression, patient eligibility is critical to treatment success. Thus, the objective of this article is to investigate the reported eligibility criteria of HT centers globally. METHODS: A systematic review of the HT literature was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines, using PubMed, Cochrane, Ovid/Medline, and Scopus. Program Web sites and clinicaltrials.gov entries were included where available. RESULTS: A total of 354 articles were reviewed, 101 of which met inclusion criteria. Furthermore, 10 patient-facing Web sites and 11 clinical trials were included. The most reported criteria related to the capacity to manage the allograft posttransplantation, including access to follow-up, insurance coverage, psychological stability, and history of medical compliance. Other factors related to the impact of immunosuppression, such as active pregnancy and patient immune status, were less emphasized. CONCLUSIONS: Because of the novelty of the field, eligibility criteria continue to evolve. While there is consensus on certain eligibility factors, other criteria diverge between programs, and very few factors were considered absolute contraindications. As the popularity of the field continues to grow, we encourage the development of consensus evidence-based eligibility criteria.

Comparative Outcomes of Malar Implants Versus Fat Transfer to Cheeks Among Transfeminine Individuals Undergoing Malar Augmentation.

BACKGROUND: Malar augmentation is a key procedure sought out by transfeminine individuals seeking to feminize their facial appearance. Different surgical techniques have been described in the literature including fat transfer to the cheeks and malar implant placement. Because of the paucity of information in the literature, there is no consensus on best practices for this procedure. The objective of our study is to determine the effectiveness and safety of malar implants as compared with fat transfer to the cheeks in transfeminine individuals. METHODS: We examined all patients with the diagnosis of gender dysphoria that were referred to the senior author seeking consultation for feminizing facial procedures between June 2017 and August 2022. Patients who underwent fat transfer to the cheeks or malar implant placement were included in our study. We reviewed the electronic medical record of each patient, and we retrieved and analyzed data regarding demographics, medical and surgical history, operative dictations, clinic notes, and postoperative follow-up. Univariate analysis was used to assess for differences in postoperative complications between these 2 groups. RESULTS: We identified 231 patients underwent feminizing facial gender affirming surgery, with 152 patients receiving malar augmentation through malar implants or fat grafting. One hundred twenty-nine patients (84.9%) underwent malar implant placement and 23 (15.1%) underwent fat grafting to the cheeks. The mean follow-up time was 3.6 ± 2.7 months. Patient satisfaction was greater in the malar implant group (126/129, 97.7%) compared with the fat transfer group (20/23, 87%, P < 0.045). Two patients who received implants (1.8%) experienced postoperative complications. No patient undergoing fat transfer experiences similar adverse outcomes. Nevertheless, the difference was not statistically significant (P = 1.00). CONCLUSIONS: Our findings support the contention that malar implants are a safe alternative for malar augmentation among transfeminine individuals. While autologous fat transfer to the cheek is an indispensable option in patients requiring minor malar enhancement, malar implants offer a more permanent option with a better aesthetic outcome in patients requiring major malar enhancement. To minimize postoperative complications, surgeons should emphasize patient compliance with postoperative directions.