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Background: International migration from high-prevalence regions has increasingly confronted nonendemic countries with female genital mutilation/cutting (FGM/C), and Western-based health care providers have seen a greater demand for surgical reconstruction of female anatomic units. The authors introduce novel surgical techniques developed by the first author for clitoral and vulvovestibular reconstruction and examine operative outcomes., Methods: The authors performed a retrospective cohort study of operative outcomes of the omega domed flap, neurotizing and molding of the clitoral stump (NMCS procedure), and anterior obturator artery perforator flap for preputial, clitoral, and vulvovestibular reconstruction, respectively. Between 2014 and 2021, the authors treated patients with all types of FGM/C, and analyzed various data, including demographics, clitoral sensation, and symptoms such as dysmenorrhea, dysuria, dyspareunia, and anorgasmia. The authors aimed to examine the efficacy and safety of these techniques in improving clitoral sensation and reducing symptoms., Results: A total of 119 women (mean age, 31.0 ± 10.4 years) were included. The authors performed the omega domed flap (85%), the NMCS procedure (82%), or the anterior obturator artery perforator flap (36%), and had a 1-year follow-up period, which was attended by 94.1% of patients. Patients reported significant postoperative reduction of dysmenorrhea, dysuria, and dyspareunia, as well as significant improvement of clitoral sensation and ability to achieve orgasm ( P < 0.001). There was 1 major complication (loss of flap) reported. Secondary ambulatory interventions were performed in 10 patients (8.4%)., Conclusion: By allowing for safe and effective anatomic reconstruction of the female genitalia, the described surgical techniques represent a new stage of treatment possibilities for women with FGM/C., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Eliciting regulated cell death, like necroptosis, is a potential cancer treatment. However, pathways eliciting necroptosis are poorly understood. It has been reported that prolonged activation of acid-sensing ion channel 1a (ASIC1a) induces necroptosis in mouse neurons. Glioblastoma stem cells (GSCs) also express functional ASIC1a, but whether prolonged activation of ASIC1a induces necroptosis in GSCs is unknown. Here we used a tumorsphere formation assay to show that slight acidosis (pH 6.6) induces necrotic cell death in a manner that was sensitive to the necroptosis inhibitor Nec-1 and to the ASIC1a antagonist PcTx1. In addition, genetic knockout of ASIC1a rendered GSCs resistant to acid-induced reduction in tumorsphere formation, while the ASIC1 agonist MitTx1 reduced tumorsphere formation also at neutral pH. Finally, a 20 amino acid fragment of the ASIC1 C-terminus, thought to interact with the necroptosis kinase RIPK1, was sufficient to reduce the formation of tumorspheres. Meanwhile, the genetic knockout of MLKL, the executive protein in the necroptosis cascade, did not prevent a reduction in tumor sphere formation, suggesting that ASIC1a induced an alternative cell death pathway. These findings demonstrate that ASIC1a is a death receptor on GSCs that induces cell death during prolonged acidosis. We propose that this pathway shapes the evolution of a tumor in its acidic microenvironment and that pharmacological activation of ASIC1a might be a potential new strategy in tumor therapy., (© 2022. The Author(s).)