International consensus recommendations on face transplantation: A 2-step Delphi study.

Face transplantation is a viable reconstructive approach for severe craniofacial defects. Despite the evolution witnessed in the field, ethical aspects, clinical and psychosocial implications, public perception, and economic sustainability remain the subject of debate and unanswered questions. Furthermore, poor data reporting and sharing, the absence of standardized metrics for outcome evaluation, and the lack of consensus definitions of success and failure have hampered the development of a "transplantation culture" on a global scale. We completed a 2-round online modified Delphi process with 35 international face transplant stakeholders, including surgeons, clinicians, psychologists, psychiatrists, ethicists, policymakers, and researchers, with a representation of 10 of the 19 face transplant teams that had already performed the procedure and 73% of face transplants. Themes addressed included patient assessment and selection, indications, social support networks, clinical framework, surgical considerations, data on patient progress and outcomes, definitions of success and failure, public image and perception, and financial sustainability. The presented recommendations are the product of a shared commitment of face transplant teams to foster the development of face transplantation and are aimed at providing a gold standard of practice and policy.

Vascularized Composite Allograft Versus Prosthetic for Reconstruction After Facial and Hand Trauma: Comparing Cost, Complications, and Long-term Outcome.

ABSTRACT: In the past decade, vascularized composite allotransplantation (VCA) has become clinical reality for reconstruction after face and hand trauma. It offers patients the unique opportunity to regain form and function in a way that had only been achieved with traditional reconstruction or with the use of prostheses. On the other hand, prostheses for facial and hand reconstruction have continued to evolve over the years and, in many cases, represent the primary option for patients after hand and face trauma. We compared the cost, associated complications, and long-term outcomes of VCA with prostheses for reconstruction of the face and hand/upper extremity. Ultimately, VCA and prostheses represent 2 different reconstructive options with distinct benefit profiles and associated limitations and should ideally not be perceived as competing choices. Our work adds a valuable component to the general framework guiding the decision to offer VCA or prostheses for reconstruction after face and upper extremity trauma.

Gynecomastia Surgery in 4996 Male Patients Over 14 Years: A Retrospective Analysis of Surgical Trends, Predictive Risk Factors, and Short-Term Outcomes.

BACKGROUND: The high prevalence of benign male breast tissue enlargement (gynecomastia) has resulted in a marked increase of gynecomastia cases. While about one third of male adults experience some form of gynecomastia, gynecomastia surgery (GS) outcome research is limited to small study populations and single-center/-surgeon databases. In this study, we aimed to access the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to identify preoperative risk factors for complications and investigate postoperative outcomes of GS. METHODS: In this retrospective study, we queried the ACS-NSQIP database from 2008 to 2021 to identify male adult patients who underwent GS. Postoperative outcomes involved the occurrence of any, surgical and medical complications, as well as reoperation, readmission, and mortality within a 30-day postoperative time period. Univariable and multivariable assessment were performed to identify risk factors for complications while adjusting for possible confounders. RESULTS: The study included 4,996 GS patients with a mean age of 33.7 ± 15 years and BMI of 28.2 ± 5.1 kg/m2. White patients constituted 54% (n = 2713) of the cohort, and 27% (n = 1346) were obese. Except for 2020, there was a steady increase in GS cases over the study period. Outpatient surgeries were most common at 95% (n = 4730), while general surgeons performed the majority of GS (n = 3580; 72%). Postoperatively, 91% (n = 4538) of patients were discharged home; 4.4% (n = 222) experienced any complications. Multivariable analysis identified inpatient setting (p < 0.001), BMI (p = 0.023), prior sepsis (p = 0.018), and bleeding disorders (p = 0.047) as independent risk factors for complications. CONCLUSION: In this study, we analyzed 4996 male adult GS patients from the ACS-NSQIP database, revealing an increased caseload and significant general surgeon involvement. Risk factors like bleeding disorders, inpatient status, and prior sepsis were linked to postoperative complications, while BMI was crucial for predicting adverse events. Overall, our findings may aid in enhancing patient care through advanced preoperative screening and closer perioperative management. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Surgical Management of Breast Capsular Contracture-A Multi-institutional Data Analysis of Risk Factors for Early Complications.

BACKGROUND: Capsular contracture (CC) is a common complication following implant-based breast surgery, often requiring surgical intervention. Yet, little is known about risk factors and outcomes following CC surgery. METHODS: We reviewed the American College of Surgeons National Surgical Quality Improvement Program database (2008-2021) to identify female patients diagnosed with CC and treated surgically. Outcomes of interest included the incidence of surgical and medical complications at 30-days, reoperations, and readmissions. Confounder-adjusted multivariable analyses were performed to establish risk factors. RESULTS: 5,057 patients with CC were identified (mean age: 55 ± 12 years and mean body mass index [BMI]: 26 ± 6 kg/m2). While 2,841 (65%) women underwent capsulectomy, capsulotomy was performed in 742 patients (15%). Implant removal and replacement were recorded in 1,160 (23%) and 315 (6.2%) cases, respectively. 319 (6.3%) patients experienced postoperative complications, with 155 (3.1%) reoperations and 99 (2.0%) readmissions. While surgical adverse events were recorded in 139 (2.7%) cases, 86 (1.7%) medical complications occurred during the 30 day follow-up. In multivariate analyses, increased BMI (OR: 1.04; p = 0.009), preoperative diagnosis of hypertension (OR: 1.48; p = 0.004), and inpatient setting (OR: 4.15; p < 0.001) were identified as risk factors of complication occurrence. CONCLUSION: Based on 14 years of multi-institutional data, we calculated a net 30 day complication rate of 6.3% after the surgical treatment of CC. We identified higher BMI, hypertension, and inpatient setting as independent risk factors of postoperative complications. Plastic surgeons may wish to integrate these findings into their perioperative workflows, thus optimizing patient counseling and determining candidates' eligibility for CC surgery. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Insights from immunoproteomic profiling of a rejected full-face transplant.

Vascularized composite allografts (VCAs) of faces and extremities are subject to chronic rejection that is incompletely understood. Here we report on immunoproteomic evaluation of a full facial VCA removed 88 months after transplantation due to chronic rejection. CD8-positive T cells of donor (graft) origin infiltrate deep intragraft arteries in apposition to degenerating endothelium of chimeric recipient origin in association with arteriosclerotic alterations. Digital spatial proteomic profiling highlighted proteins expressed by activated cytotoxic T cells and macrophages as well as pathway components involved in atherogenic responses, including Indoleamine 2,3-Dioxygenase 1 (IDO1) and Stimulator of Interferon Response CGAMP Interactor (STING). Chronic facial VCA rejection thus involves T cell/macrophage-mediated accelerated arteriosclerosis not normally represented in punch biopsies and potentially driven by persistent graft-resident effector T cells and recipient target endothelium that chimerically repopulates graft arteries.

Low-dose interleukin-2 promotes immune regulation in face transplantation: A pilot study.

Face transplantation is a life-changing procedure for patients with severe composite facial defects. However, it is hampered by high acute rejection rates due to the immunogenicity of skin allograft and toxicity linked to high doses of immunosuppression. To reduce immunosuppression-associated complications, we, for the first time in face transplant recipients, used low-dose interleukin 2 (IL-2) therapy to expand regulatory T cells (Tregs) in vivo and to enhance immune modulation, under close immunological monitoring of peripheral blood and skin allograft. Low-dose IL-2 achieved a sustained expansion (∼4-fold to 5-fold) of circulating Tregs and a reduction (∼3.5-fold) of B cells. Post-IL-2 Tregs exhibited greater suppressive function, characterized by higher expression of TIM-3 and LAG3co-inhibitory molecules. In the skin allograft, Tregs increased after low-dose IL-2 therapy. IL-2 induced a distinct molecular signature in the allograft with reduced cytotoxicity-associated genes (granzyme B and perforin). Two complications were observed during the trial: one rejection event and an episode of autoimmune hemolytic anemia. In summary, this initial experience demonstrated that low-dose IL-2 therapy was not only able to promote immune regulation in face transplant recipients but also highlighted challenges related to its narrow therapeutic window. More specific targeted Treg expansion strategies are needed to translate this approach to the clinic.

Novel Strategies in Transplantation: Genetic Engineering and Vascularized Composite Allotransplantation.

INTRODUCTION: Despite the clinical success in vascularized composite allotransplantation (VCA), systemic immunosuppression remains necessary to prevent allograft rejection. Even with potent immunosuppressive regimens (tacrolimus, mycophenolate mofetil, and steroids), most patients experience several rejection episodes, often within the same year. The risk of systemic side effects must constantly be weighed against the risk of under-immunosuppression and, thus, acute and chronic rejection. In this context, genomic editing has emerged as a potential tool to minimize the need for toxic immunosuppressive regimens and has gained attention in the fields of solid organ transplantation and xenotransplantation. This strategy may also be relevant for the future of VCA. METHODS: We discuss the topic of genetic engineering and review recent developments in this field that justify investigating tools such as clustered regularly interspaced short palindromic repeats/Cas9 in the context of VCA. RESULTS: We propose specific strategies for VCA based on the most recent gene expression data. This includes the well-known strategy of tolerance induction. Specifically, targeting the interaction between antigen-presenting cells and recipient-derived T cells by CD40 knockout may be effective. The novelty for VCA is a discovery that donor-derived T lymphocytes may play a special role in allograft rejection of facial transplants. We suggest targeting these cells prior to transplantation (e.g., by ex vivo perfusion of the transplant) by knocking out genes necessary for the long-term persistence of donor-derived immune cells in the allograft. CONCLUSION: Despite the demonstrated feasibility of VCA in recent years, continued improvements to immunomodulatory strategies using tools like clustered regularly interspaced short palindromic repeats/Cas9 could lead to the development of approaches that mitigate the limitations associated with rejection of this life-giving procedure.

An update on long-term mental health in eight face transplant recipients - A single center experience.

OBJECTIVE: Face transplantation is a groundbreaking and complex surgical intervention offering profound physical and psychological benefits to patients with severe facial disfigurements. This report provides an update on the long-term psychosocial outcome of eight face transplant recipients. METHOD: All transplant recipients were initially transplanted at Brigham and Women´s Hospital (Boston, USA) between 2011 and 2020 and are seen as outpatient patients at Yale New Haven Hospital (New Haven, USA). A mixed-methods approach was used to assess the psychological well-being of these patients. The Short-Form 12, Brief-COPE, EQ-VAS and CES-D were administered between October 2022 and October 2023. RESULTS: Older age of face transplant recipients was significantly and positively associated with better mental health and increased use of both emotional and instrumental support (Brief-COPE). The initial enhancement in patients' self-reported quality of life, as assessed by the EQVAS, declined on the EQ-VAS score at the last follow-up period. Similarly, an increase in depression score was observed (CES-D score) up through the last follow-up assessment. Both of the latter results, however, did not reach statistical significance. CONCLUSIONS: These results underscore the importance of ongoing psychological support throughout the long-term journey of recovery for face transplant recipients. They emphasized the need for a comprehensive, patient-centered approach that also addresses the complex psychological dimensions and contributes to our understanding of the mental health dynamics involved in face transplantation, underscoring the need for guidelines and continued research in this evolving field.

Perioperative Outcomes and Risk Profile of 4730 Cosmetic Breast Surgery Cases in Academic Institutions: An ACS-NSQIP Analysis.

BACKGROUND: Cosmetic breast surgery (CBS) can be subdivided into augmentation, mastopexy, reduction, and reconstruction. OBJECTIVES: The aim of this study was to retrospectively analyze a multi-institutional national database to investigate the outcomes of CBS and identify clinical patterns to optimize care. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database (2008-2020) was reviewed to identify female patients who underwent CBS. Postoperative outcomes (30-day surgical and medical complications, reoperation, readmission, and mortality) and risk factors for complications were assessed. RESULTS: In total, 4733 patients were identified (mean age, 40 [13] years; mean BMI, 24 [4.5] kg/m2) with augmentation accounting for 54% of cases. There were complications in 2.0% of cases. Age >65 years (P = .002), obesity (P < .0001), setting (P < .0001), and diabetes (P = .04) were risk factors for any complication. Age >65 years (P = .02), obesity (P = .03), diabetes (P = .01), history of chronic obstructive pulmonary disease (COPD) (P = .002) and congestive heart failure (P < .0001), smoking in the past year (P = .003), setting (P = .007), and increased American Society of Anesthesiology score (P < .0001) were predictors of surgical complications such as dehiscence and infection. Multivariable analysis confirmed that chronic obstructive pulmonary disease, obesity Class 1 and 3, and inpatient status were independent risk factors for occurrence of any complication (P = .0005, .0003, < .0001 and <.0001, respectively). Additionally, multiple procedures (P = .02) and smoking (P = .005) were found to be risk factors for surgical complications. CONCLUSIONS: This study confirms the positive safety profile of CBS. Healthy BMI is a protective factor, while complications were more likely among inpatient procedures. A correlation between multiple procedures and increased surgical complications was identified. Awareness of these risk factors can assist surgeons to further refine their perioperative protocols.

Patient-Reported Outcomes After Reduction Mammoplasty Using BREAST-Q: A Systematic Review and Meta-Analysis.

BACKGROUND: The BREAST-Q questionnaire reduction module is an established tool for outcomes after reduction mammoplasty. OBJECTIVES: This systematic review and meta-analysis assess key parameters affecting pre- and postoperative scores, with specific foci on patient characteristics and tissue resection weights. METHODS: This study was conducted per PRISMA guidelines. PUBMED (National Institutes of Health; Bethesda, MD), Google Scholar (Google; Mountain View, CA), and Web of Science (Clarivate Analytics; Philadelphia, PA) were searched. All studies published before August 1, 2021, were assessed for eligibility by 2 independent reviewers. Inclusion criteria were prospective or retrospective studies in 6 languages that reported quality of life after reduction mammoplasty employing the BREAST-Q questionnaire reduction module. Quality of included studies was assessed employing the Newcastle-Ottawa-Scale. Analysis was performed per Cochrane Collaboration and the Quality of Reporting of Meta-analyses guidelines. RESULTS: A total of 28 papers were included in the systematic review, 13 for preoperative meta-analysis, and 17 for postoperative meta-analysis. Postoperative scores in all 3 quality of life domains (psychosocial, physical, and sexual well-being) and satisfaction with breasts increased significantly after reduction mammoplasty compared with preoperative scores. Satisfaction with breasts showed the greatest improvement, from 22.9 to 73.0. Preoperative scores were lower than normative data, with improvement to comparable scores as the healthy population postoperatively. Improvements in BREAST-Q scores did not correlate with patient comorbidities, complication rates, or amount of breast tissue resected. CONCLUSIONS: Reduction mammoplasty provides marked improvement in BREAST-Q patient-reported quality of life as well established in literature. However, these improvements do not correlate with tissue resection weights, warranting further inquiry of insurance-defined resection requirements.

Software-based Detection of Acute Rejection Changes in Face Transplant.

BACKGROUND: An objective, non-invasive method for redness detection during acute allograft rejection in face transplantation (FT) is lacking. METHODS: A retrospective cohort study was performed with 688 images of 7 patients with face transplant (range, 1 to 108 months post-transplant). Healthy controls were matched to donor age, sex, and had no prior facial procedures. Rejection state was confirmed via tissue biopsy. An image-analysis software developed alongside VicarVision (Amsterdam, Netherlands) was used to produce R, a measure of differences between detectable color and absolute red. R is inversely proportional to redness, where lower R values correspond to increased redness. Linear mixed models were used to study fixed effect of rejection state on R values. Estimated marginal means of fitted models were calculated for pairwise comparisons. RESULTS: Of 688 images, 175, 170, 202, and 141 images were attributable to Banff Grade 0,1,2, and 3, respectively. Estimated change in R value of facial allografts decreased with increasing Banff Grade (p = 0.0001). The mean R value of clinical rejection (Banff Grade ⅔) (16.67, 95% Confidence Interval [CI] 14.79-18.58) was lower (p = 0.005) than non-rejection (Banff Grade 0/1) (19.38, 95%CI 17.43-21.33). Both clinical and non-rejection mean R values were lower (p = 0.0001) than healthy controls (24.12, 95%CI 20.96-27.28). CONCLUSION: This proof-of-concept study demonstrates that software-based analysis can detect and monitor acute rejection changes in FT. Future studies should expand on this tool's potential application in telehealth and as a screening tool for allograft rejection.

Full facial retransplantation in a female patient-Technical, immunologic, and clinical considerations.

There is limited experience with facial retransplantation (fRT). We report on the management of facial retransplantation in a facial vascularized composite allotransplant recipient following irreversible allograft loss 88 months after the first transplant. Chronic antibody-mediated rejection and recurrent cellular rejection resulted in a deteriorated first allograft and the patient underwent retransplantation. We summarize the events between the two transplantations, focusing on the final rejection episode. We describe the surgical technique of facial retransplantation, the immunological and psychosocial management, and the 6-month postoperative outcomes. Removal of the old allograft and inset of the new transplant were done in one operation. The donor and recipient were a good immunological match. The procedure was technically complex, requiring more proximal arterial anastomoses and an interposition vein graft. During the first and second transplantation, the facial nerve was coapted at the level of the branches. There was no hyperacute rejection in the immediate postoperative phase. Outcomes 6 months postoperatively are promising. We provide proof-of-concept that facial retransplantation is a viable option for patients who suffer irreversible facial vascularized composite allograft loss.

The modified 5-item frailty index is a predictor of perioperative risk in head and neck microvascular reconstruction: An analysis of 3795 cases.

BACKGROUND: The modified frailty index 5 (mFI-5)-a scale based on the five variables diabetes, hypertension, chronic obstructive pulmonary disease, congestive heart failure, and functional dependency-has been shown to be a valid predictor of surgical outcomes. In this study we sought to evaluate the ability of the mFI-5 to predict the postoperative outcomes of head and neck microvascular reconstruction. METHODS: Review of the 2015-2019 American College of Surgeons, National Surgical Quality Improvement Program (ACS NSQIP) database identified 5323 cases of microvascular reconstruction, of which 3795 were head and neck cases that provided parameters necessary to calculate the mFI-5. The groups were compared in terms of demographics and comorbidities. Post-operative outcomes assessed included mortality, average operative time and length of hospital stay, surgical and medical complications, and non-home discharge. RESULTS: Increases in the mFI were associated with longer hospitalization periods (10.5 ± 7.5 days in mFI 0 vs 14.9 ± 15.4 in mFI ≥ 3; p < 0.0001) higher rates of mortality (1% in mFI 0 vs 3.1% in mFI ≥ 3; p = 0.02), reoperation (15.4% in mFI 0 vs 17.2% in mFI ≥ 3; p = 0.002) and unplanned readmission (7.6% in mFI 0 vs 18.8% in mFI ≥ 3; p = 0.001). Rates of any complications (p < 0.0001), as well as surgical (p < 0.002) and medical (p < 0.0001) complications specifically were higher with greater mFI scores. Higher mFI scores also predicted decreased home discharge (p < 0.0001). Differences remained significant on multivariate analysis and subgroup analysis by age. CONCLUSION: The mFI-5 is a significant predictor of risk in microvascular head and neck reconstruction. Subgroup analysis by age highlights that the tool can help identify younger patients who are frail and hence at risk. Through appropriate pre-operative identification of frail patients surgeons can prospectively modify their operative and discharge planning as well as post-operative support.

Use of venous couplers in microsurgical lower extremity reconstruction: A systematic review and meta-analysis.

BACKGROUND: Free tissue transfer for lower limb reconstruction has become a workhorse procedure for limb-salvage. Compared with other recipient sites, the lower extremity has a higher risk of microvascular complications, in particular with venous anastomosis. The study's objective is to evaluate the evidence, safety, and efficacy of venous coupler use in microsurgical anastomosis in lower limb reconstruction to provide objective appraisal of the surgical techniques. METHODS: A systematic review (SR) and meta-analysis (MA) were performed analyzing articles from PubMed, Cochrane, Embase, and Web of Science from January 1990, to August 2018. Abstracts and titles were screened and assessed for eligibility by independent reviewers. Following full-text review, articles were included in the SR and MA. Case reports were excluded. Cochrane Collaboration and the Quality of Reporting of Meta-analyses (QUOROM) guidelines were followed. RESULTS: Out of 15 included studies that met the inclusion criteria for the SR, 9 were included in MA. Patients treated with venous couplers did not experience more surgical complications (risk ratio (RR) 0.79; 95% confidence interval (CI) 0.48-1.33; p = .38), total failure (RR 0.61; 95% CI 0.22-1.70; p = .34), venous compromise (RR 0.72; 95% CI 0.23-2.27; p = .57), arterial compromise (RR 0.85; 95% CI 0.25-2.88; p = .80), partial failure (RR 0.77; 95% CI 0.33-1.77; p = .54), or reoperation (RR 11.79; 95% CI 0.49-286.55; p = .13) in comparison with hand-sewn anastomosis. CONCLUSIONS: Outcomes of venous couplers in lower limb reconstruction are comparable to those of hand-sewn anastomosis. However, this study was limited by the quality of the available literature. Additional prospective studies should aim to directly compare both techniques and potential further benefits in clinical trials.

Chronic rejection of human face allografts.

Face vascularized composite allografts (FVCAs) have helped patients with severe facial disfigurement, with acute rejection now largely controlled through iatrogenic immunosuppression. However, little is known regarding the incidence and mechanism(s) of more long-term pathologic alterations in FVCAs that may affect function and graft durability. Protocol surveillance biopsy specimens for up to an 8-year interval in 7 patients who received FVCAs at our institution revealed histopathologic evidence of chronic rejection. Clinical manifestations included features of premature aging, mottled leukoderma accentuating suture lines, telangiectasia, and dryness of nasal mucosa. Pathologic changes consisted of epidermal thinning accompanied by discrete foci of lymphocyte-mediated cytotoxicity, hyperkeratosis, follicular plugging, vascular ectasia, and sclerosis beneath the epidermal layer associated with collagen type I deposition. Genomic interrogation and immunohistochemistry of sclerotic zones revealed upregulation of the AP-1 pathway components, JunB and c-Fos, previously implicated in overproduction of type I dermal collagen in the setting of systemic sclerosis. We conclude that some patients develop chronic rejection in FVCAs with striking similarities to alterations seen in certain autoimmune cutaneous disorders (lupus erythematosus and scleroderma/chronic sclerodermoid graft-versus-host disease). Identification of relevant pathways and genes, such as JunB and c-Fos, may provide new targets for preventative therapies for chronic immune-mediated changes in vascularized composite allografts.

Software-based video analysis of functional outcomes of face transplantation.

INTRODUCTION: Assessment of outcomes after face transplantation (FT) is necessary to provide sound evidence on the benefits of this life-giving surgery. Current methods for outcomes assessment, however, are imprecise or prone to subjectivity. Software-based video analysis may allow fast, objective and retrospective assessment of restoration of facial movements and functions after FT. PATIENTS AND METHODS: We recorded videos of 7 subjects before as well as every 3-6 months after facial transplantation. Patients performed the same sequence of facial movements in every video: smile, open mouth, purse lips, wrinkle nose, frown, close eyes, and lift eyebrows. The videos were retrospectively analyzed using EMOTIENT software, which is capable of automatic tracking and detailed measurements of facial movements and expressions. These measurements were subsequently compared to the same patient at different time points, as well as to the normal population. RESULTS: Open mouth, wrinkle nose and smile functions significantly improved in all patients when compared to pre-transplant functions; this improvement was significant at 3, 6, and 12 months after transplant, respectively. Lip purse, eye closure and frown functions improved by 6, 9, and 18 months after transplantation, respectively; however, improvement in these particular functions was not significantly with respect to pre-transplant. Face transplantation did not improve any of the patients' ability to lift their eyebrows. Most remarkably, mouth opening and smiling functions both reached values comparable to the normal population at 3 and 12 months after transplantation, respectively. CONCLUSION: Software-based video analysis provides a valuable assessment tool capable of objective, precise and reproducible analysis of facial movements and functions after FT.

The Collagenase of the Bacterium Clostridium histolyticum in the Treatment of Irradiation-Induced Capsular Contracture.

BACKGROUND: Irradiation therapy is an important pillar in the treatment of breast cancer. However, it can trigger capsular fibrosis, the most significant complication of implant-based breast reconstruction. As collagen is the main component of fibrotic capsules, the collagenase of the bacterium Clostridium histolyticum poses a potential treatment option for this pathological condition. METHODS: Thirty-six rats received miniature silicone implants on their backs. On day 1, the implant sites of two groups were irradiated with 10 Gy. On day 120, one irradiated group received collagenase injections into the implant pockets (n = 12). Non-irradiated (n = 12) and irradiated capsules (n = 12) were injected with plain solvent solution serving as controls. Data were analyzed by means of in vivo imaging, histology, immunohistochemistry and gene expression analysis. RESULTS: Compared with both controls, the injection of collagenase led to significantly thinner capsules. This was verified by in vivo imaging and histology. Although irradiation provoked alterations in capsule collagen structure and vessel wall thickness, the application of collagenase resulted in a significant reduction of collagen density. This was accompanied by an up-regulation of VEGF-A gene expression. Of note, hematoma formation inside the implant pocket occurred in two cases after collagenase injection. CONCLUSIONS: The collagenase of the bacterium Clostridium histolyticum is effective in degrading irradiation-induced capsular fibrosis around silicone implants. Hematoma formation occurred most likely because of irradiation-induced alterations in vessel wall architecture and capsule vascularization. Further studies need to be performed to address the clinical safety of this novel treatment option.

Novel immunological and clinical insights in vascularized composite allotransplantation.

PURPOSE OF REVIEW: Vascularized composite allotransplantation (VCA) is a promising approach to restore the quality of life of carefully selected patients that suffered extensive injury. Although acute rejection occurs very frequently, still little is known about the specific characteristics of the VCA immune response. This review aims to highlight the current development in the field of VCA concerning the immunobiology and management of upper extremity and face transplant recipients. RECENT FINDINGS: T-cell mediated rejection is the predominant mechanism of allograft injury in VCA. As current histological classification does not differentiate types of rejection, novel evidence using NanoString has determined a molecular signature that helps identify antibody-mediated rejection in comparison to T-cell mediated rejection. Additionally, long-term follow-up of VCA patients progressively reveals various features of chronic rejection, and novel immunosuppressive approaches such as costimulation blockade found its way into immunosuppressive regimens of VCA recipients, unraveling its potential benefits as well as limitations. Finally, novel noninvasive biomarkers were recently evaluated and showed promise to differentiate the severity of acute rejection, and consequently, the intensity of treatment required. SUMMARY: With growing knowledge about the immunobiology in VCA, novel approaches to immunosuppressive therapy and immune monitoring will help better manage patients and improve long-term VCA outcomes.