Gender-affirming vaginoplasty (GAV) comprises the construction of a vulva and a neovaginal canal. Although technical nuances of vulvar construction vary between surgeons, vulvar construction is always performed using the homologous penile and scrotal tissues to construct the corresponding vulvar structures. Therefore, the main differentiating factor across gender-affirming vaginoplasty techniques is the tissue that is utilized to construct the neovaginal canal. These tissue types vary markedly in their availability, histology, and ease of harvest and have different advantages and disadvantages to their use as neovaginal lining. In this narrative review, the authors provide a comprehensive overview of the tissue types and associated operative approaches used for construction of the neovagina in GAV. Tissue choice is guided by several factors, such as histological similarity to natal vaginal mucosa, tissue availability, lubrication potential, additional donor site morbidity, and the specific goals of each patient. Skin is used to construct the neovagina in most cases with a combination of pedicled penile skin flaps and scrotal and extra-genital skin grafts. However, skin alternatives such as peritoneum and intestine are increasing in use. Peritoneum and intestine are emerging as options for primary vaginoplasty in cases of limited genital skin or revision vaginoplasty procedures. The increasing number of gender-affirming vaginoplasty procedures performed and the changing patient demographics from factors such as pubertal suppression have resulted in rapidly evolving indications for the use of these differing vaginoplasty techniques. This review sheds light on the use of less frequently utilized tissue types described for construction of the neovaginal canal, including mucosal tissues such as urethral and buccal mucosa, the tunica vaginalis, and dermal matrix allografts and xenografts. Although the body of evidence for each vaginoplasty technique is growing, there is a need for large prospective comparison studies of outcomes between these techniques and the tissue types used to line the neovaginal canal to better define indications and limitations.

Introduction: Some patients pursuing gender-affirming mastectomy prefer to forgo autologous nipple and areolar reconstruction, instead choosing a “no nipple” option. The objective of this study is to evaluate the motives and influences contributing to this decision. Methods: A retrospective survey-based study of patients undergoing gender-affirming mastectomy over a 4.6-year period was conducted. All patients were offered nipple and areolar reconstruction. A survey was distributed to those who elected to forgo nipple and areolar reconstruction exploring the factors influencing that choice and postoperative satisfaction. Results: Five hundred thirty-six patients underwent gender-affirming mastectomy and 13% chose to forgo nipple and areolar reconstruction. The survey response rate was 72%. Most respondents identified as nonbinary (48%) or transmasculine (42%). Body image, defined in the context of this study as an improvement in body image satisfaction due to achievement of a more gender-congruent appearance, was the most highly cited and most heavily weighted decision-making factor. Concerns about nipple graft outcomes were frequently cited as important but carried less weight. There were no differences between transmasculine and nonbinary patients in terms of motivations for choosing this surgical option. Fifty-eight percent of respondents pursued or planned to pursue chest tattoos, whereas 42% preferred no further chest modifications. Patient satisfaction was high postoperatively (98%), and 82% of respondents would choose to forgo nipple and areolar reconstruction again even if surgical outcomes of free nipple grafts were improved. Conclusions: Gender-affirming mastectomy without nipple and areolar reconstruction was requested by 13% of patients presenting for gender-affirming chest surgery over the study period and had high postoperative satisfaction among patients who chose this option. This modification of gender-affirming mastectomy is a variation that surgical teams should be aware of. Many reasons to forgo nipple preservation were cited, most of which related to body image. Secondary factors were easier recovery and/or concern about outcomes of free nipple grafts. Many patients wished information about this surgical option was more widely available.

Persistent activation of cardiac fibroblasts into myofibroblasts drives excessive extracellular matrix deposition, leading to maladaptive myocardial fibrosis, adverse remodeling and heart failure (HF) progression. Adipocyte enhancer binding protein 1 (AEBP1) and Aortic carboxypeptidase-like protein (ACLP, full-length AEBP1 protein coded by AEBP1 ) has been implicated in pathological fibrosis across multiple organs, with tissue-specific knockdown attenuating fibrosis in preclinical models. Although elevated AEBP1 expression has been associated with human HF, its role in myocardial fibrosis progression in vivo remains undefined. Here, we demonstrated that AEBP1 is a critical mediator of myocardial fibrosis and adverse cardiac remodeling. Fibroblast-specific knockout and cardiac-specific knockdown of Aebp1 si gnificantly improved cardiac function and prevented pathological remodeling in murine models of myocardial ischemia and pressure-overload induced injury. In ex vivo human myocardial tissue culture studies, ACLP overexpression in non-failing hearts induced pathological remodeling, whereas AEBP1 knockdown in failing human hearts induced structural reverse remodeling. Mechanistically, we also showed that ACLP regulates key pro-fibrotic transcription factors and genes, including MRTFB, RUNX2, SM22 and COL1A1, thereby orchestrating fibroblast activation. Collectively, these findings establish AEBP1 as a central driver of myocardial fi brosis and highlights its inhibition as a promising therapeutic strategy to mitigate both acute and chronic HF.

Background: Little has been published on the histomorphometry of the human dorsal nerve of the penis (DNP), despite its growing importance in peripheral nerve surgeries aimed at restoring lost penile sensation or erectile function, and in gender-affirming surgeries which rely on the glans penis to reconstruct the neoclitoris with minimal histomorphometric data currently available to inform technique. Aim: To quantify the number of axons in the human DNP and discuss potential clinical implications. Methods: Bilateral DNP samples were obtained from 12 fresh frozen cadavers at the level of the inferior aspect of the pubic symphysis. Specimens were fixed and stained using validated techniques. Histomorphometric evaluation was performed at 1000× magnification using image analysis software to obtain myelinated nerve fiber count, fascicle number, and density. Outcomes: Primary outcomes included myelinated axon count, fascicle number, and nerve fiber density of the DNP. Results: Twenty-three DNP samples were analyzed. The mean axon count was 3634 (SD = 1575) with a range of 6299. Accounting for the bilaterality of the DNP, the mean total number of axons innervating the human glans penis was 7076 axons (SD = 2634 axons). The total myelinated axon count, fascicle number, and nerve density did not differ significantly by laterally, nor did these parameters differ significantly between individuals. Myelinated axon counts of the DNP were on average less than previously reported axon counts for the dorsal nerve of clitoris using identical methodology, despite the much larger size of the glans penis. The axon counts of the DNP varied more between individuals than demonstrated in our prior work on the dorsal nerve of clitoris. Clinical Implications: These findings may suggest that variability in DNP axon composition may be one factor giving rise to outcome variability in nerve-based reconstructive and sensory restoration procedures and inform techniques in neoclitoris construction in gender-affirming genital surgery. Strengths and Limitations: Unmyelinated axons are not counted using the technique employed. Samples were obtained from fresh frozen cadavers which may introduce heterogeneity into the tissue samples obtained. Conclusion: This study reports axon count, fascicle number, and nerve density of the human DNP and discusses the clinical relevance therein.