Cosmetic Revision Surgeries after Transfeminine Vaginoplasty.

BACKGROUND: Vaginoplasty is the most frequent genital gender-affirming surgery. Although both functional and aesthetic outcomes after transfeminine vaginoplasty have improved over the years, cosmetic revision surgeries demand after transfeminine vaginoplasty appears to be increasing and requires updated knowledge. METHODS: All patients who underwent vulvar cosmetic revision surgeries at our institution following transfeminine vaginoplasty from January 2014 to April  2022 were studied. The prevalence, topography and surgical techniques of cosmetic revision surgeries after transfeminine genital gender-affirming surgery were examined using clinical charts review and statistical analysis. RESULTS: During the study period, 354 patients underwent gender-affirming vaginoplasty at our single institution (212 penile inversion vaginoplasty, 122 colovaginoplasty and 20 penile inversion vaginoplasty with scrotal skin graft patients). Forty out of these 354 patients (11.29%) required cosmetic revision surgery after transfeminine vaginoplasty; additionally, 44 patients with vaginoplasty performed at other centres also underwent vulvar cosmetic revision surgery at our clinic during the study period. From all performed cosmetic revision surgeries, most of them (31.42%) were labia corrections, followed by clitoris (23.26%) repair surgeries. Mons Venus (10.20%), urethral meatus (9.38%), spongiosus tissue remnants (8.57%) and introitus (6.53%) revisions followed in frequency. Corrections of peri-inguinal scars (5.30%), anterior commissure (2.84%) and inferior fourchette (2.42%) were less prevalent. No differences were found among the different studied vaginoplasty techniques regarding cosmetic revision surgery prevalence or topography following transfeminine vaginoplasty (p < 0.05). CONCLUSIONS: Cosmetic revision surgeries after transfeminine vaginoplasty are frequent. In our large and long-term cohort study, labiaplasty followed by clitoroplasty were found as the most required cosmetic revision surgical procedures. Further multicentre, prospective and controlled studies are necessary to improve cosmetic outcomes and scientific evidence after transfeminine vaginoplasty. LEVEL OF EVIDENCE IV: 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 .

The use of dermal substitutes in burn surgery: acute phase.

Major burns represent a challenge in autologous skin coverage and may lead to severe functional and cosmetic sequelae. Dermal substitutes are increasingly becoming an essential part of burn care during the acute phase of treatment. In the long term dermal substitutes improve functional and cosmetic results and thus enhance quality of life. In the chronic wound setting, dermal substitutes are used to reconstruct and improve burn scars and defects. Despite the potential of dermal substitutes, further research is required to strengthen scientific evidence regarding their effects and also to develop new technologies and products. Furthermore, dermal substitutes have a pivotal role in future research strategies as they have the potential to provide adequate scaffold for stem cells, tissue engineering, and regenerative medicine with conceivable application of obtaining long-lasting and scarless artificial skin. This review discusses the status quo of dermal substitutes and novel strategies in the use of dermal substitutes with a focus on burn care.

Effects of metformin on burn-induced hepatic endoplasmic reticulum stress in male rats.

Severe burn injury causes hepatic dysfunction that results in major metabolic derangements including insulin resistance and hyperglycemia and is associated with hepatic endoplasmic reticulum (ER) stress. We have recently shown that insulin reduces ER stress and improves liver function and morphology; however, it is not clear whether these changes are directly insulin mediated or are due to glucose alterations. Metformin is an antidiabetic agent that decreases hyperglycemia by different pathways than insulin; therefore, we asked whether metformin affects postburn ER stress and hepatic metabolism. The aim of the present study is to determine the effects of metformin on postburn hepatic ER stress and metabolic markers. Male rats were randomized to sham, burn injury and burn injury plus metformin and were sacrificed at various time points. Outcomes measured were hepatic damage, function, metabolism and ER stress. Burn-induced decrease in albumin mRNA and increase in alanine transaminase (p < 0.01 versus sham) were not normalized by metformin treatment. In addition, ER stress markers were similarly increased in burn injury with or without metformin compared with sham (p < 0.05). We also found that gluconeogenesis and fatty acid metabolism gene expressions were upregulated with or without metformin compared with sham (p < 0.05). Our results indicate that, whereas thermal injury results in hepatic ER stress, metformin does not ameliorate postburn stress responses by correcting hepatic ER stress.

Fenofibrate does not affect burn-induced hepatic endoplasmic reticulum stress.

BACKGROUND: Burn injury causes major metabolic derangements such as hypermetabolism, hyperlipidemia, and insulin resistance and is associated with liver damage, hepatomegaly, and hepatic endoplasmic reticulum (ER) stress. Although the physiological consequences of such derangements have been delineated, the underlying molecular mechanisms remain unknown. Previously, it was shown that fenofibrate improves patient outcome by attenuating postburn stress responses. METHODS: Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, regulates liver lipid metabolism and has been used to treat hypertriglyceridemia and hypercholesterolemia for many years. The aim of the present study is to determine the effects of fenofibrate on burn-induced hepatic morphologic and metabolic changes. We randomized rats to sham, burn injury, and burn injury plus fenofibrate. Animals were sacrificed and livers were assessed at 24 or 48 h post burn. RESULTS: Burn injury decreased albumin and increased alanine transaminase (P = 0.1 versus sham), indicating liver injury. Fenofibrate administration did not restore albumin or decrease alanine transaminase. In addition, ER stress was significantly increased after burn injury both with and without fenofibrate (P < 0.05 versus sham). Burn injury increased fatty acid metabolism gene expression (P < 0.05 versus sham), downstream of peroxisome proliferator-activated receptor alpha. Fenofibrate treatment increased fatty acid metabolism further, which reduced postburn hepatic steatosis (burn versus sham P < 0.05, burn + fenofibrate versus sham not significant). CONCLUSIONS: Fenofibrate did not alleviate thermal injury-induced hepatic ER stress and dysfunction, but it reduced hepatic steatosis by modulating hepatic genes related to fat metabolism.

Functional, aesthetic, and sensory postoperative complications of female genital gender affirmation surgery: A prospective study.

BACKGROUND: Female genital gender affirmation surgeries have increased in recent years. Prospective studies with homogeneous standardized techniques and outcomes assessment are scarce in the current literature. This study aims to: 1) report the functional, aesthetic, and sensory postoperative complications (POCs) of primary genital gender confirmation surgeries performed on transgender women and 2) compare functional and aesthetic POCs amongst three vaginoplasty techniques: inverted penile skin, penoscrotal skin graft, and pedicled intestinal flap vaginoplasty. METHODS: All (n = 84) consecutive transfemale individuals who underwent primary genital gender confirmation surgery from January 2015 to December 2016 at IMCLINIC were prospectively followed. Functional, aesthetic, and sensory POCs were registered according to the Clavien-Dindo POC classification. RESULTS: Functional POC rates after vaginoplasty at our centre were 19%, 12%, 13%, and 1% at short (one month), mid-early (three months), mid-late (six months), and long-term (one year) follow-up visits, respectively. None of them were severe complications (grades IV-V), 25% were grade III, and less than 20% were low-grade complications (grades I-II). Overall, aesthetic satisfaction was high (90%). The total number of secondary surgeries needed to satisfy the cosmetic outcome was 20 (aesthetic POC grade IIIb). No differences regarding functional or aesthetic complication rates amongst vaginoplasty techniques were encountered. Twelve months after surgery, 81% of patients had initiated sexual intercourse, and 96% reported clitoral sensitivity. CONCLUSIONS: In our experience, female genital gender affirmation surgery is a feasible, low-complication surgery that offers high satisfaction in the long term. Further multicentric well-designed research is mandatory to improve outcomes.

Full face transplant: the first case report.

BACKGROUND: Since 2005, 11 human face transplants have been performed. In each, varying amounts of tissue have been transplanted. Herein we report a "full" face transplant including all intact aesthetic and functional units. METHODS: On March 27, 2010, we performed a full face transplant, including all the soft tissues and part of the underlaying bony structure, at the University Hospital Vall d'Hebron, Barcelona, Spain. The donor was a 41-year-old male, who died from a massive brain hemorrhage. The recipient was a 30-year-old male with a severe facial deformity caused by a ballistic trauma in 2005. Harvest and subsequent implant took 24 hours. The patient received initial induction (Thymoglobulin 2 mg/kg/iv; Prednisone 1 gm/iv) and maintenance (Prednisone 1 mg/kg/24hours, Tacrolimus 10-15 ng/mL/PO, and Mycophenolate mofetil 2g/daily/PO) immunosuppression and Infection prophylaxis (Valganciclovir and Co-trimoxazole). RESULTS: There were no intraoperative complications. Postoperative complications included; venous anastomoses thrombosis, acute oro-cutaneous fistula, right parotid sialocele and 2 acute rejection episodes, which were resolved by revision of the anastomosis, profuse irrigation and immunotherapy adjustment, respectively. The patient was discharged from the hospital at 4 months posttransplant with; near-total sensation and partial-motor recovery, no psychological complications and excellent acceptance of his new facial appearance. CONCLUSIONS: The early success described in this case report demonstrates the technical and clinical feasibility of transplanting all the tissues of the with all its aesthetic and functional units intact.

New molecular medicine-based scar management strategies.

Keloids and hypertrophic scars are prevalent disabling conditions with still suboptimal treatments. Basic science and molecular-based medicine research have contributed to unravel new bench-to-bedside scar therapies and to dissect the complex signalling pathways involved. Peptides such as the transforming growth factor beta (TGF-ß) superfamily, with Smads, Ski, SnoN, Fussels, endoglin, DS-Sily, Cav-1p, AZX100, thymosin-ß4 and other related molecules may emerge as targets to prevent and treat keloids and hypertrophic scars. The aim of this review is to describe the basic complexity of these new molecular scar management strategies and point out new fibrosis research lines.

Up-to-date approach to manage keloids and hypertrophic scars: a useful guide.

Keloids and hypertrophic scars occur anywhere from 30 to 90% of patients, and are characterized by pathologically excessive dermal fibrosis and aberrant wound healing. Both entities have different clinical and histochemical characteristics, and unfortunately still represent a great challenge for clinicians due to lack of efficacious treatments. Current advances in molecular biology and genetics reveal new preventive and therapeutical options which represent a hope to manage this highly prevalent, chronic and disabling problem, with long-term beneficial outcomes and improvement of quality of life. While we wait for these translational clinical products to be marketed, however, it is imperative to know the basics of the currently existing wide array of strategies to deal with excessive scars: from the classical corticotherapy, to the most recent botulinum toxin and lasers. The main aim of this review paper is to offer a useful up-to-date guideline to prevent and treat keloids and hypertrophic scars.

Human Wharton's jelly mesenchymal stem cells promote skin wound healing through paracrine signaling.

INTRODUCTION: The prevalence of nonhealing wounds is predicted to increase due to the growing aging population. Despite the use of novel skin substitutes and wound dressings, poorly vascularized wound niches impair wound repair. Mesenchymal stem cells (MSCs) have been reported to provide paracrine signals to promote wound healing, but the effect of human Wharton's jelly-derived MSCs (WJ-MSCs) has not yet been described in human normal skin. METHODS: Human WJ-MSCs and normal skin fibroblasts were isolated from donated umbilical cords and normal adult human skin. Fibroblasts were treated with WJ-MSC-conditioned medium (WJ-MSC-CM) or nonconditioned medium. RESULTS: Expression of genes involved in re-epithelialization (transforming growth factor-ß2), neovascularization (hypoxia-inducible factor-1α) and fibroproliferation (plasminogen activator inhibitor-1) was upregulated in WJ-MSC-CM-treated fibroblasts (P≤0.05). WJ-MSC-CM enhanced normal skin fibroblast proliferation (P≤0.001) and migration (P≤0.05), and promoted wound healing in an excisional full-thickness skin murine model. CONCLUSIONS: Under our experimental conditions, WJ-MSCs enhanced skin wound healing in an in vivo mouse model.

Effect of human Wharton's jelly mesenchymal stem cell paracrine signaling on keloid fibroblasts.

Keloid scars are abnormal benign fibroproliferative tumors with high recurrence rates and no current efficacious treatment. Accumulating evidence suggests that human umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have antifibrotic properties. Paracrine signaling is considered one of the main underlying mechanisms behind the therapeutic effects of mesenchymal stem cells. However, the paracrine signaling effects of WJ-MSCs on keloids have not yet been reported. The aim of this study is to investigate paracrine signaling effects of human WJ-MSCs on keloid fibroblasts in vitro. Human umbilical cords and keloid skin samples were obtained, and WJ-MSCs and keloid fibroblasts were isolated and cultured. One-way and two-way paracrine culture systems between both cell types were investigated. Plasminogen activator inhibitor-I and transforming growth factor-ß2 (TGF-ß2) transcripts were upregulated in keloid fibroblasts cultured with WJ-MSC-conditioned medium (WJ-MSC-CM) and cocultured with inserts, while showing lower TGF-ß3 gene expression. Interleukin (IL)-6, IL-8, TGF-ß1, and TGF-ß2 protein expression was also enhanced. The WJ-MSC-CM-treated keloid fibroblasts showed higher proliferation rates than their control keloid fibroblasts with no significant change in apoptosis rate or migration ability. In our culture conditions, the indirect application of WJ-MSCs on keloid fibroblasts may enhance their profibrotic phenotype.

Face allotransplantation and burns: a review.

Burns may represent one of the main indications for face allotransplantation. Severely disfigured faces featuring a devastating appearance and great functional impairments are not only seen as burn sequelae but also occur as a result of other traumatic injuries, oncological surgical resections, benign tumors (eg, neurofibromatosis), and major congenital malformations. To date, 20 human face composite tissue allotransplants have been performed with success. Despite the initial scepticism about its applicability, due mainly to ethical and technical reasons, the previous worldwide cases and their associated positive outcomes, including acceptable immunosuppressive regimens, excellent aesthetic and functional results, and good psychological acceptance by the recipient, enable the conclusion that face composite tissue allotransplantation has become another therapeutic strategy in the reconstructive surgical armamentarium, which bears special consideration when dealing with severely disfigured burned patients. The aim of this review is to describe the basics of face composite tissue allotransplantation and give an overview of some of the cases performed until now, with special attention paid to debating the pros and cons of its applicability in burn patients.

Stem Cell Therapy: A New Treatment for Burns?

Stem cell therapy has emerged as a promising new approach in almost every medicine specialty. This vast, heterogeneous family of cells are now both naturally (embryonic and adult stem cells) or artificially obtained (induced pluripotent stem cells or iPSCs) and their fates have become increasingly controllable, thanks to ongoing research in this passionate new field. We are at the beginning of a new era in medicine, with multiple applications for stem cell therapy, not only as a monotherapy, but also as an adjunct to other strategies, such as organ transplantation or standard drug treatment. Regrettably, serious preclinical concerns remain and differentiation, cell fusion, senescence and signalling crosstalk with growth factors and biomaterials are still challenges for this promising multidisciplinary therapeutic modality. Severe burns have several indications for stem cell therapy, including enhancement of wound healing, replacement of damaged skin and perfect skin regeneration - incorporating skin appendages and reduced fibrosis -, as well as systemic effects, such as inflammation, hypermetabolism and immunosuppression. The aim of this review is to describe well established characteristics of stem cells and to delineate new advances in the stem cell field, in the context of burn injury and wound healing.