Testosterone promotes nerve tethering and acellular biomaterial perineural fibrosis in a rat wound repair model.

OBJECTIVE: Nerve scarring after traumatic or iatrogenic exposure can lead to impaired function and pain. Nerve-adjacent biomaterials promoting a regenerative tissue response may help reduce perineural fibrosis. Our prior work suggests testosterone may promote fibrotic skin scarring, but it is unknown how testosterone alters nerve fibrosis or shifts the response to biomaterials. APPROACH: Sterilized Lewis rats received either testosterone cypionate (+T) or placebo (-T) biweekly. Fifteen days later, wounds were created over the sciatic nerve and covered with acellular extracellular matrix (AM) or closed primarily (PC). At day 42, force gauge testing measured the force required to mobilize the nerve and wound tissue was analyzed. RESULTS: Nerve mobilization force was greater in +T vs -T wounds (p<0.01). Nerves tore before gliding in 60% of +T vs 6% of -T rats. Epidermal gap (p<0.01), scar width (p<0.01), and cross-sectional scar tissue area (p=0.02) were greater in +T vs -T rats. -T vs +T rats expressed more Col-3 (p=0.02) and CD68 (p=0.02). Nerve mobilization force trended non-significantly higher for PC versus AM wounds and for +T versus -T wounds within the AM cohort. INNOVATION: Testosterone increases nerve tethering in the wound healing milieu, altering repair and immune cell balances. CONCLUSION: Testosterone significantly increases the force required to mobilize nerves in wound beds and elevates histologic markers of scarring, suggesting that testosterone-induced inflammation may increase perineural adhesion. Testosterone may reduce the potential anti-tethering protective effect of AM. Androgen receptor antagonism may represent a therapeutic target to reduce scar-related nerve morbidity.

The Impact of Breast Implant Cohesivity on Rippling and Revision Procedures in 2-Stage Prepectoral Breast Reconstruction.

Background: Rippling remains one of the most common complications following prepectoral implant-based reconstruction (IBR). Objectives: The purpose of this study was to assess how implant cohesivity, a measure of elasticity and form stability, affects the incidence of rippling in prepectoral IBR. Methods: We performed a retrospective cohort study of 2-stage prepectoral IBR performed between January 2020 and June 2022 at the Brigham and Women's Hospital and Dana-Farber Cancer Institute, comparing outcomes in patients who received Allergan Natrelle least cohesive, moderately cohesive, and most cohesive silicone gel implants. Outcomes of interest were rippling and reoperation for fat grafting. Results: A total of 129 patients were identified, of whom 52 had the least cohesive implants, 24 had the moderately cohesive implants, and 53 patients had the most cohesive implants. The mean follow-up time was 463 (±220) days. A decreased incidence of rippling was seen with moderately cohesive (odds ratio [OR] 0.30, P < .05) and most cohesive (OR 0.39, P < .05) implants. Third stage reoperation for fat grafting was less frequent in patients with the most cohesive implant (OR 0.07, P < .05). In subgroup analyses, the patients with the most cohesive implant, who did not receive fat grafting at the time of initial implant placement, did not require reoperation for fat grafting (0%). Conclusions: The use of highly cohesive implants in prepectoral IBR is associated with decreased rippling and fewer reoperations for fat grafting.

Androgenic steroids induce pathologic scarring in a preclinical porcine model via dysfunctional extracellular matrix deposition.

Hypertrophic scarring is a major source of morbidity. Sex hormones are not classically considered modulators of scarring. However, based on increased frequency of hypertrophic scarring in patients on testosterone, we hypothesized that androgenic steroids induce abnormal scarring and developed a preclinical porcine model to explore these effects. Mini-swine underwent castration, received no testosterone (noT) or biweekly testosterone therapy (+T), and underwent excisional wounding. To create a delayed wound healing model, a subset of wounds were re-excised at 2 weeks. Scars from postoperative day 42 (POD42) and delayed wounds (POD28) were harvested 6 weeks after initial wounding for analysis via histology, bulk RNA-seq, and mechanical testing. Histologic analysis of scars from +T animals showed increased mean fibrosis area (16 mm2noT, 28 mm2+T; p = .007) and thickness (0.246 mm2noT, 0.406 mm2+T; p < .001) compared to noT. XX+T and XY+T scars had greater tensile burst strength (p = .024 and p = .013, respectively) compared to noT swine. Color deconvolution analysis revealed greater deposition of type I and type III collagen as well as increased collagen type I:III ratio in +T scars. Dermatopathologist histology scoring showed that +T exposure was associated with worse overall scarring (p < .05). Gene ontology analysis found that testosterone exposure was associated with upregulation of cellular metabolism and immune response gene sets, while testosterone upregulated pathways related to keratinization and laminin formation on pathway analysis. In conclusion, we developed a preclinical porcine model to study the effects of the sex hormone testosterone on scarring. Testosterone induces increased scar tissue deposition and appears to increase physical strength of scars via supraphysiologic deposition of collagen and other ECM factors. The increased burst strength seen in both XX and XY animals suggests that hormone administration has a strong influence on scar mechanical properties independent of chromosomal sex. Anti-androgen topical therapies may be a promising future area of research.

Bard Versus the 2022 American Society of Plastic Surgeons In-Service Examination: Performance on the Examination in Its Intern Year.

Background: Bard is a conversational generative artificial intelligence (AI) platform released by Google (Mountain View, CA) to the public in May 2023. Objectives: This study investigates the performance of Bard on the American Society of Plastic Surgeons (ASPS) In-Service Examination to compare it to residents' performance nationally. We hypothesized that Bard would perform best on the comprehensive and core surgical principles portions of the examination. Methods: Google's 2023 Bard was used to answer questions from the 2022 ASPS In-Service Examination. Each question was asked as written with the stem and multiple-choice options. The 2022 ASPS Norm Table was utilized to compare Bard's performance to that of subgroups of plastic surgery residents. Results: A total of 231 questions were included. Bard answered 143 questions correctly corresponding to an accuracy of 62%. The highest-performing section was the comprehensive portion (73%). When compared with integrated residents nationally, Bard scored in the 74th percentile for post-graduate year (PGY)-1, 34th percentile for PGY-2, 20th percentile for PGY-3, 8th percentile for PGY-4, 1st percentile for PGY-5, and 2nd percentile for PGY-6. Conclusions: Bard outperformed more than half of the first-year integrated residents (74th percentile). Its best sections were the comprehensive and core surgical principle portions of the examination. Further analysis of the chatbot's incorrect questions might help improve the overall quality of the examination's questions.

"Revision Phalloplasty: Evaluation, Algorithms and Techniques for Salvage After Major Complications".

BACKGROUND: Phalloplasty is among the most complex and technically demanding reconstructive surgeries. As a larger pool of surgeons perform this difficult procedure, more patients will present with major complications. There is little published on the comprehensive evaluation and management of these patients, particularly those needing correction of multiple ongoing complications, which may require consideration of starting over with a new microsurgical procedure versus salvage of the existing flap. METHODS: A literature review on complications of phalloplasty was conducted in combination with drawing upon the experience of two high-volume phalloplasty teams (Johns Hopkins/Brigham & Women's Hospital and GU Recon/Buncke Clinic) in treating patients with severe post-surgical issues. The purpose was to analyze critical factors and develop algorithms for secondary revision. RESULTS: Common complications of phalloplasty include urethral strictures and fistulae, diverticula, excess bulk, phalloplasty malposition, hypertrophic/keloidal scarring, and partial/total flap loss. In severe cases, local flaps or free flaps may be required for reconstruction. The decision to revise the existing neophallus or start over with a new flap for phalloplasty is particularly critical. Multidisciplinary team collaboration is essential to develop comprehensive plans that will resolve multiple concomitant problems while meeting patient goals for a functional and aesthetic neophallus. CONCLUSIONS: Preserving the original flap for phalloplasty is ideal when feasible. Additional local or free flaps are sometimes necessary in situations of significant tissue loss. In severe cases, complete redo phalloplasty is required. The algorithms proposed provide a conceptual framework to guide surgeons in analyzing and managing severe complications following phalloplasty.

A Novel Mouse Model for Investigating the Effects of Gender-affirming Hormone Therapy on Surgical Healing.

Wound healing problems are a major cause of morbidity for gender-affirming surgery (GAS) patients. Prior studies have shown sex differences in wound healing may exist. We hypothesized exogenous testosterone supplementation may impair post-GAS wound healing and developed a model to investigate this phenomenon. Mice were randomized by hormone regimen and gonadectomy (OVX). Gonadectomy or sham occurred on day 0 and mice were assigned to no testosterone (-T), mono- or bi-weekly (T/2T) testosterone groups. Dorsal splinted wounding occurred on day 14 and harvest on day 21. Serum testosterone levels were quantified with mass spectrometry. Tissue underwent analysis with planimetry, qPCR, ELISA, and immunofluorescence. Mean testosterone trough levels for bi-weekly regimen were higher compared to mono-weekly (397 versus 272 ng/dL; P = 0.027). At POD5, 2T injections led to 24.9% and 24.7% increases in mean wound size relative to SHAM and OVX/-T, respectively (P = 0.004; 0.001). Wounds in OVX/+2T mice demonstrated increased gene expression for inflammatory cytokines and macrophage marker F4/80 (P < 0.05). ELISA confirmed elevated wound TNFα levels (P < 0.05). Quantitative multiplex immunofluorescence with F4/80/NOS2/ARG1 showed significant increases in macrophage prevalence in OVX/+2T (P < 0.05). We developed a novel model of GAS hormonal milieu to study effects of exogenous testosterone on wound healing. Optimized twice-weekly dosing yielded serum levels comparable to clinical therapy. We showed exogenous testosterone administered to XX/OVX mice significantly impairs wound healing. A hyperinflammatory wound environment results in increased macrophage proliferation and elevated cytokines. Future efforts are directed toward mechanistic investigation and clinical validation.