Complications and management of excessive phallic turgor following gender-affirming phalloplasty.

Gender-affirming phalloplasty involves flap tubularization, placing unique stresses on the vascularity of the flap. Tubularization renders the flap susceptible to postoperative edema that can lead to excessive turgor that, if left untreated, can compromise perfusion and threaten the viability of the phallic reconstruction. This phenomenon has not been formally described in our literature. We aim to define this entity, described here as "Excessive Phallic Turgor" (EPT), and to outline its incidence, frequency of its underlying etiologies, and sequelae. We conducted a single-center, retrospective review of all phalloplasty operations involving flap transfer performed from December 2016 to May 2023. All patients requiring emergent intervention (bedside suture release, reoperation, or both) due to excessive phallic swelling and impending flap compromise were considered to have EPT. Variables compared between groups included underlying etiology (categorized as congestion, hematoma or swelling), patient demographics, flap type and size, management, length of stay, and postoperative outcomes. Over the study period, 147 phalloplasty operations involving flap transfer for shaft creation were performed. Of those, 15% developed EPT. Age, BMI, flap length, flap circumference, flap surface area, single vs multistage operation, flap tubularization (shaft-only vs tube-within-tube), and flap donor site were not significantly different between the cohort that developed EPT and that which did not. Development of EPT was associated with higher rates of phallic hematoma, surgical site infection, shaft fistula requiring repair, and longer inpatient stays. When EPT develops, prompt diagnosis and alleviation of intraphallic pressure are paramount for mitigating short- and long-term morbidity.

Neurosensory Re-education following Gender-affirming Phalloplasty: A Novel Treatment Protocol.

Sensory nerve transfers are performed as part of phalloplasty surgery. Despite this, sensory re-education to rehabilitate these nerve transfers has not been employed. Additionally, little attention has been paid to the role of the central nervous system in experienced sensation following phalloplasty. The purpose of this article is to report on the development of a targeted rehabilitation protocol to integrate and optimize peripheral and central contributions to sensation following phalloplasty. Methods: This neurosensory re-education protocol was constructed over four phases by a multi-disciplinary team (phalloplasty/peripheral nerve surgeon, reconstructive urologist, pelvic floor physiotherapists, nerve therapist, sex therapist, sexual medicine physician) and individuals with lived phalloplasty experience. The final protocol was approved by all team members and is supported here by qualitative narratives from people with lived phalloplasty experience. Results: The protocol is built to follow each stage of phalloplasty surgery. In each stage, exercises are grouped into three core themes: visualization, tactile stimulation, and sexual/erogenous stimulation. Visualization exercises progress from static to dynamic. Tactile exercises start at simple touch and progress toward targeted sensory stimulation. Sexual stimulation focuses on developing erogenous sensation in the phallus that is separate from erogenous sensation in the natal clitoral tissue. By recommendation of individuals with phalloplasty, the protocol is now integrated into our center's phalloplasty care pathway for all individuals undergoing phalloplasty surgery. Conclusion: We introduce a novel protocol targeting peripheral and central contributions to sensation to provide a tool to help optimize experienced sensation for transmasculine individuals undergoing phalloplasty.

Technical Description and Microsurgical Outcomes in Phalloplasty Using the Deep Inferior Epigastric Artery and Locoregional Veins.

BACKGROUND: Phalloplasty often requires free tissue transfer. There is ample literature describing flap-related outcomes, but the microsurgical technique used, including choice of recipient vessels, has been an overlooked yet important topic. In this study, the authors review the outcomes of their experience with the deep inferior epigastric artery and locoregional veins and outline technical modifications that occurred during the study period. METHODS: A retrospective chart analysis of patients who underwent microsurgical phalloplasty between September of 2016 and July of 2019 was performed. Variables included flap design, donor site, and recipient vessels. The outcome measures were return to the operating room for flap compromise and partial or complete flap loss. RESULTS: Forty-two phalloplasties using the deep inferior epigastric artery were identified. There were six take-backs for flap compromise, and four patients required venous revision, one of whom lost his urethral flap on postoperative day 9. There was a decrease in take-back rate from 30 percent in the first 20 patients to 0 percent in the second 22 patients in the study period. A total of 11.9 percent of patients had partial flap loss. This decreased from 15 percent to 9 percent in the two groups. CONCLUSION: After an initial learning curve, the combination of deep inferior epigastric artery, deep inferior epigastric vein, and great saphenous vein combined with specific technical modifications such as targeted coagulation of the vasa nervorum of the clitoral nerve has proven to be a reliable technique. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Masculinizing Genital Surgery: An Imaging Primer for the Radiologist.

OBJECTIVE. Masculinizing genital surgeries for transgender individuals are currently performed at only a select few centers; however, radiologists in any geographic region may be confronted with imaging studies of transgender patients. The imaging findings of internal and external genital anatomy of a transgender patient may differ substantially from the imaging findings of a cisgender patient. This article provides the surgical and anatomic basis to allow appropriate interpretation of preoperative and postoperative imaging findings. We also expand on the most common complications and associated imaging findings. CONCLUSION. As these procedures become more commonplace, radiologists will have a growing role in the care of transgender patients and will be faced with new anatomic variants and differential diagnoses. Familiarity with these anatomic variations and postoperative complications is crucial for the radiologist to provide an accurate and useful report.

Nasal obstruction symptom evaluation (NOSE) score outcomes after septorhinoplasty.

OBJECTIVES/HYPOTHESIS: The time interval at which Nasal Obstruction Symptom Evaluation (NOSE) scores stabilize after functional septorhinoplasty has not been determined. Our goal was to characterize longitudinal trends of patient-reported outcomes of nasal obstruction using the NOSE survey instrument following functional septorhinoplasty. STUDY DESIGN: Prospective longitudinal cohort study. METHODS: Adult patients (≥18 years) with nasal obstruction who underwent functional septorhinoplasty by three different surgeons at a single academic, tertiary referral center were identified. NOSE scores were obtained preoperatively and prospectively during three postoperative intervals defined as early (1-3 months), middle (4-6 months), and late (≥10 months.) Longitudinal analysis included repeated measures analysis of variance and adjustments for multiple comparisons. RESULTS: A total of 49 patients met inclusion criteria. For the total cohort, mean NOSE scores significantly improved between preoperative and early postoperative evaluations (71.4, standard deviation [SD] ± 17.0 vs. 24.2, SD ± 19.5; P < .001) but did not significantly change between early and middle (20.6, SD ± 19.1; P = .543) or middle and late (23.1, SD ± 24.9; P > .999) time intervals. CONCLUSIONS: Patients with nasal obstruction who undergo functional septorhinoplasty can be expected to have significant improvement in self -reported nasal obstruction as early as 1 to 3 months postoperatively with a continued, durable, long-standing benefit lasting at least 10 months after surgery. Future studies can consider the 3-month time frame as a proxy for 1 year outcomes to help reduce survey burden. LEVEL OF EVIDENCE: 2c Laryngoscope, 129:841-846, 2019.

What is "Nonbinary" and What Do I Need to Know? A Primer for Surgeons Providing Chest Surgery for Transgender Patients.

BACKGROUND: Most transgender research focuses on patients who identify within the gender binary of either trans-male or trans-female. This largely omits understanding of the "nonbinary" gender identity as it pertains to surgical care. OBJECTIVES: We sought to describe a single-institution experience of chest-affirming procedures performed in nonbinary patients, including patient characteristics, surgical techniques, practice pearls, and outcomes. METHODS: This was an observational study of nonbinary patients who underwent "chest-affirming surgery" from 2012 to 2017. Demographic and surgical data were collected. A postoperative questionnaire assessing quality of life and body image outcomes was administered. RESULTS: A total of 458 patients with gender dysphoria underwent chest surgery; 58 (13%) patients were nonbinary. All nonbinary patients indicated female sex was assigned at their birth (100%). The most commonly performed procedure was the double incision technique with nipple grafts (72%), followed by the double incision technique without nipple grafts (19%). On a Likert scale, patients reported improved quality of life (4.88, SD ± 0.34), comfort with exercise (4.07, SD ± 0.98), sex life (4.02, SD ± 0.92), and comfort with physical appearance with (4.97, SD ± 0.18) and without clothes (4.69, SD ± 0.47). CONCLUSIONS: Chest surgery for nonbinary patients comprises a considerable proportion of transgender surgery practice, and surgeons who provide affirming care should be familiar with the unique characteristics and treatment options for this population.

Probing the Effects of Gating on the Ion Occupancy of the K+ Channel Selectivity Filter Using Two-Dimensional Infrared Spectroscopy.

The interplay between the intracellular gate and the selectivity filter underlies the structural basis for gating in potassium ion channels. Using a combination of protein semisynthesis, two-dimensional infrared (2D IR) spectroscopy, and molecular dynamics (MD) simulations, we probe the ion occupancy at the S1 binding site in the constricted state of the selectivity filter of the KcsA channel when the intracellular gate is open and closed. The 2D IR spectra resolve two features, whose relative intensities depend on the state of the intracellular gate. By matching the experiment to calculated 2D IR spectra of structures predicted by MD simulations, we identify the two features as corresponding to states with S1 occupied or unoccupied by K+. We learn that S1 is >70% occupied when the intracellular gate is closed and <15% occupied when the gate is open. Comparison of MD trajectories show that opening of the intracellular gate causes a structural change in the selectivity filter, which leads to a change in the ion occupancy. This work reveals the complexity of the conformational landscape of the K+ channel selectivity filter and its dependence on the state of the intracellular gate.

Instantaneous ion configurations in the K+ ion channel selectivity filter revealed by 2D IR spectroscopy.

Potassium channels are responsible for the selective permeation of K+ ions across cell membranes. K+ ions permeate in single file through the selectivity filter, a narrow pore lined by backbone carbonyls that compose four K+ binding sites. Here, we report on the two-dimensional infrared (2D IR) spectra of a semisynthetic KcsA channel with site-specific heavy (13C18O) isotope labels in the selectivity filter. The ultrafast time resolution of 2D IR spectroscopy provides an instantaneous snapshot of the multi-ion configurations and structural distributions that occur spontaneously in the filter. Two elongated features are resolved, revealing the statistical weighting of two structural conformations. The spectra are reproduced by molecular dynamics simulations of structures with water separating two K+ ions in the binding sites, ruling out configurations with ions occupying adjacent sites.

Individual Ion Binding Sites in the K(+) Channel Play Distinct Roles in C-type Inactivation and in Recovery from Inactivation.

The selectivity filter of K(+) channels contains four ion binding sites (S1-S4) and serves dual functions of discriminating K(+) from Na(+) and acting as a gate during C-type inactivation. C-type inactivation is modulated by ion binding to the selectivity filter sites, but the underlying mechanism is not known. Here we evaluate how the ion binding sites in the selectivity filter of the KcsA channel participate in C-type inactivation and in recovery from inactivation. We use unnatural amide-to-ester substitutions in the protein backbone to manipulate the S1-S3 sites and a side-chain substitution to perturb the S4 site. We develop an improved semisynthetic approach for generating these amide-to-ester substitutions in the selectivity filter. Our combined electrophysiological and X-ray crystallographic analysis of the selectivity filter mutants show that the ion binding sites play specific roles during inactivation and provide insights into the structural changes at the selectivity filter during C-type inactivation.

Engineering the glutamate transporter homologue GltPh using protein semisynthesis.

Glutamate transporters catalyze the concentrative uptake of glutamate from synapses and are essential for normal synaptic function. Despite extensive investigations of glutamate transporters, the mechanisms underlying substrate recognition, ion selectivity, and the coupling of substrate and ion transport are not well-understood. Deciphering these mechanisms requires the ability to precisely engineer the transporter. In this study, we describe the semisynthesis of GltPh, an archaeal homologue of glutamate transporters. Semisynthesis allows the precise engineering of GltPh through the incorporation of unnatural amino acids and peptide backbone modifications. In the semisynthesis, the GltPh polypeptide is initially assembled from a recombinantly expressed thioester peptide and a chemically synthesized peptide using the native chemical ligation reaction followed by in vitro folding to the native state. We have developed a robust procedure for the in vitro folding of GltPh. Biochemical characterization of the semisynthetic GltPh indicates that it is similar to the native transporter. We used semisynthesis to substitute Arg397, a highly conserved residue in the substrate binding site, with the unnatural analogue, citrulline. Our studies demonstrate that Arg397 is required for high-affinity substrate binding, and on the basis of our results, we propose that Arg397 is involved in a Na+-dependent remodeling of the substrate binding site required for high-affinity Asp binding. We anticipate that the semisynthetic approach developed in this study will be extremely useful in investigating functional mechanisms in GltPh. Further, the approach developed in this study should also be applicable to other membrane transport proteins.