Feminization of the Forehead: A Scoping Literature Review and Cohort Study of Transfeminine Patients.

BACKGROUND: Facial feminization may be performed to alleviate gender dysphoria among transfeminine patients. The upper third of the face has several characteristics, including hairline shape and position, brow position, and forehead protrusion, that may confer feminine identity. The purpose of this study is to conduct a scoping literature review of techniques performed for forehead feminization and to additionally study clinical outcomes within an institutional cohort. METHODS: A systematic literature review was conducted to review articles that discussed techniques and clinical outcomes associated with procedures performed for feminization of the upper third of the face. A retrospective review of patients undergoing such procedures by the senior author was then conducted. Variables collected included demographic factors, operative details, and postoperative outcomes such as complications, revisions, and re-operations. RESULTS: Initial review yielded sixty-seven articles. Title and abstract review followed by standardized application of inclusion and exclusion criteria resulted in a total of twenty-two studies for analysis. Priorities of forehead feminization entail frontal bossing reduction, frontonasal angle widening, orbital contouring, brow lifting, and hairline advancement. Eighty-five patients were included for analysis. The majority were of Caucasian race (56%) and had type 3 forehead classification (92%). The average planned setback of the anterior table was 4.12 mm. CONCLUSIONS: The core tenets of the feminization of the forehead lie in the overall creation of a harmonic curvature of the forehead with other facial features. Our multi-pronged analysis presents an updated review of these principles, which may help plastic surgeons in performing procedures to feminize the upper third of the face. LEVEL OF EVIDENCE III: 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 Table of Contents or online Instructions to Authors www.springer.com/00266.

Medicaid coverage for gender-affirming surgery: A state-by-state review.

OBJECTIVE: To systematically review Medicaid policies state-by-state for gender-affirming surgery coverage. DATA SOURCES AND STUDY SETTING: Primary data were collected for each US state utilizing the LexisNexis legal database, state legislature publications, and Medicaid manuals. STUDY DESIGN: A cross-sectional study evaluating Medicaid coverage for numerous gender-affirming surgeries. DATA COLLECTION/EXTRACTION METHODS: We previously reported on state health policies that protect gender-affirming care under Medicaid coverage. Building upon our prior work, we systematically assessed the 27 states with protective policies to determine coverage for each type of gender-affirming surgery. We analyzed Medicaid coverage for gender-affirming surgeries in four domains: chest, genital, craniofacial and neck reconstruction, and miscellaneous procedures. Medicaid coverage for each type of surgery was categorized as explicitly covered, explicitly noncovered, or not described. PRINCIPAL FINDINGS: Among the 27 states with protective Medicaid policies, 17 states (63.0%) provided explicit coverage for at least one gender-affirming chest procedure and at least one gender-affirming genital procedure, while only eight states (29.6%) provided explicit coverage for at least one craniofacial and neck procedure (p = 0.04). Coverage for specific surgical procedures within these three anatomical domains varied. The most common explicitly covered procedures were breast reduction/mastectomy and hysterectomy (n = 17, 63.0%). The most common explicitly noncovered surgery was reversal surgery (n = 12, 44.4%). Several states did not describe the specific surgical procedures covered; thus, final coverage rates are indeterminate. CONCLUSIONS: In 2022, 52.9% of states had health policies that protected gender-affirming care under Medicaid; however, coverage for various gender-affirming surgical procedures remains both variable and occasionally unspecified. When specified, craniofacial and neck reconstruction is the least covered anatomical area compared with chest and genital reconstruction.

Ethnic variation in lower face anthropometry on facial computed tomography scans for patients seeking facial feminization surgery.

BACKGROUND: Facial feminization surgery (FFS) is the most common form of facial gender-affirming surgery. One of the current knowledge gaps is the understanding of differences among racial groups in baseline craniofacial norms for transgender and nonbinary patients. METHODS: All patients who sought consultation for FFS and underwent craniofacial computed tomography (CT) scans at a single institution between 2018 and 2023 were included. Patients who underwent previous facial surgeries were excluded. Chart reviews were conducted for patient characteristics, including race, age, hormone therapy duration, and prior gender-affirming surgeries. Racial categorizations included White, Latinx, African American, or Asian. Patients with other or multiracial identities were excluded. Lower face measurements were derived from preoperative facial CT scans. Comparative analyses were performed on all measurements among the racial groups. RESULTS: In this study, 204 patients were included with an average age of 32.0 ± 10.2 years and a median hormone therapy duration of 2.0 years. The notable differences among the racial groups were: 1. Zygomatic width was the largest in Asian patients (13.5 ± 0.6 cm) compared to all other racial groups (p = 0.03), 2. Nasolabial angle was the smallest in African American patients (82.5 ± 13.1 degrees, p < 0.001), 3. Lower face height was the largest in African American patients (6.9 ± 0.7 cm, p < 0.001), and 4. Lateral mandibular flare was the largest in African American patients (0.4 ± 0.1 cm) and the smallest in Latinx patients (0.2 ± 0.1 cm, p < 0.001). CONCLUSIONS: Specific target areas of FFS should be carefully considered to account for possible baseline ethnic differences. Relative facial proportions may also be a more salient surgical planning tool in transgender and gender nonbinary patients rather than absolute measurements alone.

Floating electrode-dielectric barrier discharge-based plasma promotes skin regeneration in a full-thickness skin defect mouse model.

Wound healing involves a complex and dynamic interplay among various cell types, cytokines, and growth factors. Macrophages and transforming growth factor-ß1 (TGF-ß1) play an essential role in different phases of wound healing. Cold atmospheric plasma has a wide range of applications in the treatment of chronic wounds. Hence, we aimed to investigate the safety and efficacy of a custom-made plasma device in a full-thickness skin defect mouse model. Here, we investigated the wound tissue on days 6 and 12 using histology, qPCR, and western blotting. During the inflammation phase of wound repair, macrophages play an important role in the onset and resolution of inflammation, showing decreased F4/80 on day 6 of plasma treatment and increased TGF-ß1 levels. The plasma-treated group showed better epidermal epithelialization, dermal fibrosis, collagen maturation, and reduced inflammation than the control group. Our findings revealed that floating electrode-dielectric barrier discharge (FE-DBD)-based atmospheric-pressure plasma promoted significantly faster wound healing in the plasma-treated group than that in the control group with untreated wounds. Hence, plasma treatment accelerated wound healing processes without noticeable side effects and suppressed pro-inflammatory genes, suggesting that FE-DBD-based plasma could be a potential therapeutic option for treating various wounds.

Preoperative Radiology and Virtual Surgical Planning.

Virtual surgical planning enables precise surgical planning and translation of this planning into the operating room. Preoperative maxillofacial computed tomography scans are compared to a reference skull to identify desired surgical changes. In facial feminization surgery, these include forehead recontouring/frontal table setback, gonial angle reduction, and possible chin repositioning/reshaping, while in facial masculinization surgery, this includes forehead augmentation and gonial angle/chin augmentation. Cutting and recontouring guides as well as custom implants are then custom manufactured. Common guides include osteotomy guides, depth drilling guides, ostectomy guides, and guides for one/two-piece genioplasty or chin burring. Common implants include mandibular and chin implants.

United States Health Policies on Gender-Affirming Care in 2022.

BACKGROUND: Within the United States, access to gender-affirming operations covered by health insurance has increased dramatically over the past decade. However, the perpetually changing landscape and inconsistencies of individual state health policies governing private and public insurance coverage present a lack of clarity for reconstructive surgeons and other physicians attempting to provide gender-affirming care. This work systematically reviewed the current U.S. health policies for both private insurance and Medicaid on a state-by-state basis. METHODS: Individual state health policies in effect as of August of 2022 on gender-affirming care were reviewed using the LexisNexis legal database, state legislature publications, and Medicaid manuals. Primary outcomes were categorization of policies as protective, restrictive, or unclear for each state. Secondary outcomes included analyses of demographics covered by current health policies and geographic differences. RESULTS: Protective state-level health policies related to gender-affirming care were present in approximately half of the nation for both private insurance (49.0%) and Medicaid (52.9%). Explicitly restrictive policies were found in 5.9% and 17.6% of states for private insurance and Medicaid, respectively. Regionally, the Northeast and West had the highest rates of protective policies, whereas the Midwest and South had the highest rates of restrictive policies on gender-affirming care. CONCLUSIONS: State-level health policies on gender-affirming care vary significantly across the United States with regional associations. Clarity in the current and evolving state-specific health policies governing gender-affirming care is essential for surgeons and physicians caring for transgender and gender-diverse individuals.

Assessing Preferences of Facial Appearance in Transgender and Gender Nonbinary Patients.

BACKGROUND: We designed a survey to evaluate preferences of facial appearance in transgender male (TM), transgender female (TF) and gender nonbinary patients to better inform goals of facial gender affirming surgery (FGAS) in gender nonbinary patients. METHODS: TM/TF and nonbinary patients > 18 years old were identified via retrospective chart review and distributed an anonymized survey via email from October 3 to December 31, 2022. To assess facial preferences, AI-generated and open-source portraits were edited to create five image sets with a range of features from masculine to feminine for the forehead, mandible/chin and hairline. Data were analyzed using Fisher's exact tests and ANOVA in R-Studio. RESULTS: Survey response rate was 32% (180 patients identified via chart review, 58 respondents; TM = 5, TF = 39, nonbinary = 14). TM and TF patients as well as TF and nonbinary patients had significantly different preferences for all regions (p < 0.005; all series), while TM and nonbinary patients did not (p => 0.05; all series). TF patients consistently selected 4s with neutral or more feminine features. TM and nonbinary patients, however, demonstrated no consistent preference for either male or female features but rather a range of responses spanning extremes of both masculine and feminine options. When stratified by sex assigned at birth, nonbinary patients consistently identified preferences opposite to their assigned gender. CONCLUSION: Gender nonbinary and TM patients appear to have uniquely individual preferences regarding facial appearance that do not fit into classically masculine or feminine patterns/phenotypes. As a result, we recommend individualized preoperative planning for FGAS to achieve the optimal result in these patient populations. 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 .

Long-term outcomes of sphincter pharyngoplasty in patients with cleft palate.

OBJECTIVE: The purpose of this study was to evaluate long-term outcomes of sphincter pharyngoplasties, including speech outcomes, revision surgeries, and postoperative incidence of obstructive sleep apnea (OSA). DESIGN: Retrospective matched-cohort study SETTING: Two craniofacial centers in Los Angeles, CA PATIENTS: Patients (n = 166) with cleft lip and palate (CLP) or isolated cleft palate (iCP) who underwent sphincter pharyngoplasty from 1992 to 2022 were identified. An age- and diagnosis-matched control group of 67 patients with CLP/iCP without velopharyngeal insufficiency (VPI) was also identified. INTERVENTIONS: The pharyngoplasty group underwent sphincter pharyngoplasty, whereas the non-VPI group had no history of VPI surgery or sphincter pharyngoplasty. MAIN OUTCOME MEASURES: Postoperative speech outcomes, revision surgeries, and incidence of OSA were evaluated. Multivariable regression was used to evaluate independent predictors of OSA. RESULTS: Among the patients in the pharyngoplasty cohort, 63.9% demonstrated improved and sustained speech outcomes after a single pharyngoplasty, with a median postoperative follow-up of 8.8 years (interquartile range [IQR], 3.6-12.0 years). One-third of the patients who underwent pharyngoplasty required a revision surgery, with a median time to primary revision of 3.9 years (IQR, 1.9-7.0 years). OSA rates increased significantly among the pharyngoplasty cohort, from 3% before surgery to 14.5% after surgery (p < 0.001). The average time from sphincter pharyngoplasty to OSA diagnosis was 4.4 ± 2.4 years. Multivariable analysis results indicated that sphincter pharyngoplasty surgery was independently associated with a fourfold increase in OSA (p = 0.03). CONCLUSIONS: Although sphincter pharyngoplasty remains successful in improving long-term speech outcomes, persistent OSA is a sequela that should be monitored beyond the immediate postoperative period.

Bone-Anchored Maxillary Protraction for Adolescents with Cleft Palate and Class III Malocclusion: A Case Series.

To describe the long-term treatment course of bone-anchored maxillary protraction (BAMP) and evaluate orthognathic surgical indications after BAMP.Retrospective case series.Craniofacial/Cleft Palate Program at the Orthopaedic Institute for Children in Los Angeles, CA.Twelve male patients with cleft palate (CP), unilateral cleft lip and palate (UCLP), or bilateral cleft lip and palate (BCLP) and Class III malocclusion treated with BAMP (mean age: 11.4 ± 2.6 years) were included.BAMP treatment was performed by placement of bone-anchored maxillary and mandibular plates connected with intraoral Class III dental elastics or maxillary plates connected to a facemask.We retrospectively assessed BAMP treatment variables, including age at surgery, revision surgeries, and treatment duration. The primary goal was correction to class I occlusion.Twelve patients underwent BAMP treatment for an average of 4.4 ± 2.4 years. Two patients were corrected to class I occlusion at the time of this report. Le Fort I advancement was no longer required in two patients (16.7%), it was required for nine patients (75.0%) and was completed for one patient following BAMP treatment (8.3%).This preliminary report demonstrated that BAMP treatment may be associated with a minimal reduction in the requirement for Le Fort I advancement at skeletal maturity. Future studies with larger sample sizes are necessary to confirm this association.

Duration of Feminizing Hormone Therapy on Facial Fat Volumes.

BACKGROUND: Gender-affirming feminizing hormone therapy induces body fat redistribution. However, the amount and timing of facial fat changes in response to feminizing hormone therapy are unknown, albeit relevant to counseling and surgical planning for facial gender-affirming surgery. In this work, we assessed the influence of feminizing hormone therapy duration on malar and temporal fat volume. METHODS: Malar and temporal fat volumes were compared using computed tomography in transfeminine patients (age 20-29 years, body mass index [BMI] 18.5-24.9) treated with feminizing hormone therapy for <2 years versus ≥2 years. Patients with prior surgical or non-surgical facial soft-tissue interventions were excluded. Multivariable linear regressions evaluated the contribution of hormone therapy duration to malar and temporal fat volumes. RESULTS: 45 patients were included with 30 patients (66.7%) treated with feminizing hormone therapy for ≥2 years and 15 patients (33.3%) treated for <2 years (median[interquartile range, IQR]: 44.5[33.5-65.6] vs. 15.0[11.0-18.0] months, p<0.001). Patients treated with hormone therapy for ≥2 years demonstrated a 1.6-fold greater malar fat volume (5.5[4.2-6.3] vs. 3.4[2.3-4.2] cm 3,p<0.001) and 1.4-fold greater temporal fat volume (2.8[2.4-3.6] cm 3 vs. 2.0[1.7-2.4] cm 3, p=0.01) compared to those treated for <2 years. When accounting for other contributory variables such as BMI, skull size, and total soft-tissue depth in multivariable linear regression models, hormone therapy duration ≥2 years independently predicted higher malar (ß=0.51, p<0.001) and temporal (ß=0.32, p=0.02) fat volumes. CONCLUSIONS: Feminizing hormone therapy increases malar and temporal fat volumes by approximately 2 cm 3 and 0.8 cm 3 for each area, respectively, after 2 years of treatment.

Meta-Analysis and Meta-Regression of Complications and Failures of Autologous Heterotopic Cranial Bone versus Alloplastic Cranioplasties.

BACKGROUND: Fresh autologous cranial bone graft has been traditionally regarded as the ideal cranioplasty material, however long-term comparisons of outcomes with modern alloplastic materials are absent in the literature. In this work, we evaluated complications and failures among cranioplasties performed with fresh, heterotopic, cranial bone graft versus three common alloplastic materials. METHODS: Random-effects meta-analyses of logit-transformed proportions were performed on studies published between 1971-2021 to evaluate complications and failures of cranioplasties performed with fresh, autologous, heterotopic cranial bone, polyetheretherketone (PEEK), polymethylmethacrylate (PMMA), or titanium with a mean follow-up ≥12 months. Generalized mixed model meta-regressions were performed to account for heterogeneity and to evaluate the contributions of moderators to outcomes variables. RESULTS: 1490 patients (mean age 33.9±10.8 years) were included. Pooled, all-cause complications were 6.2% for fresh, heterotopic, autologous cranial bone (95% confidence interval [CI]:2.1-17.0%; I2=55.0%, p=0.02), 18.5% for PEEK (95%CI:14.0-24.0%; I2=0.0%, p=0.58), 26.1% for titanium (95%CI:18.7-35.1%; I2=60.6%, p<0.01), and 28.4% for PMMA (95%CI:12.9-51.5%; I2=88.5%, p<0.01). Pooled all-cause failures were 2.2% for fresh, autologous cranial bone (95%CI:0.4-10.6%; I2=0.0%, p=0.45), 6.3% for PEEK (95%CI:3.2-12.3%; I2=15.5%, p=0.31), 11.4% for titanium (95%CI:6.7-18.8%; I2=60.8%, p<0.01), and 12.7% for PMMA (95%CI:6.9-22.0%; I2=64.8%, p<0.01). Meta-regression models indicated that each alloplastic subtype significantly and independently predicted higher complications, while titanium and PMMA were significant predictors for all-cause failures compared to autologous bone. All three subtypes were predictive of higher cranioplasty failures secondary to infection compared to autologous bone. CONCLUSIONS: Cranioplasties performed with fresh, autologous heterotopic cranial bone grafts resulted in lower complications and failures compared to alloplastic materials.

An enhanced recovery after surgery protocol for facial feminization surgery reduces perioperative opioid usage, pain, and hospital stay.

BACKGROUND: Prescription drug misuse in transgender individuals is estimated to be three times higher than that of the general population in the United States, suggesting that opioid-reduction strategies deserve significant consideration in gender-affirming surgeries. In this work, we describe the implementation of an enhanced recovery after surgery (ERAS) protocol to reduce opioid use after facial feminization surgery. METHODS: A total of 79 patients who underwent single-stage facial feminization surgery before (n = 38) or after (n = 41) ERAS protocol implementation were included. Primary outcomes assessed were perioperative opioid consumption (morphine equivalent dose/kilogram, MED/kg), average patient-reported pain scores, and length of hospital stay. Comparisons between groups and multivariable linear regression analyses were conducted to define the contribution of the ERAS protocol to each of the three primary outcomes. RESULTS: Age, body mass index, mental health diagnoses, and length of surgery did not differ between pre-ERAS and ERAS groups. Compared to pre-ERAS patients, patients treated under the ERAS protocol consumed less opioids (median [interquartile range, IQR], 0.8 [0.5-1.1] versus 1.5 [1.0-2.1] MED/kg, p < 0.001), reported lower pain scores (2.5 ± 1.8 versus 3.7 ± 1.6, p = 0.002), and required a shorter hospital stay (median [IQR], 27.3 [26.3-49.8] versus 32.4 [24.8-39.1] h, p < 0.001). When controlling for other contributing variables such as previous gender-affirming surgeries, mental health diagnoses, and length of surgery using multivariable linear regression analyses, ERAS protocol implementation independently predicted reduced opioid use, lower pain scores, and shorter hospital stay after facial feminization surgery. CONCLUSIONS: The current work details an ERAS protocol for facial feminization surgery that reduces perioperative opioid consumption, patient-reported pain scores, and hospital stays.

Convergence of Calcium Channel Regulation and Mechanotransduction in Skeletal Regenerative Biomaterial Design.

Cells are known to perceive their microenvironment through extracellular and intracellular mechanical signals. Upon sensing mechanical stimuli, cells can initiate various downstream signaling pathways that are vital to regulating proliferation, growth, and homeostasis. One such physiologic activity modulated by mechanical stimuli is osteogenic differentiation. The process of osteogenic mechanotransduction is regulated by numerous calcium ion channels-including channels coupled to cilia, mechanosensitive and voltage-sensitive channels, and channels associated with the endoplasmic reticulum. Evidence suggests these channels are implicated in osteogenic pathways such as the YAP/TAZ and canonical Wnt pathways. This review aims to describe the involvement of calcium channels in regulating osteogenic differentiation in response to mechanical loading and characterize the fashion in which those channels directly or indirectly mediate this process. The mechanotransduction pathway is a promising target for the development of regenerative materials for clinical applications due to its independence from exogenous growth factor supplementation. As such, also described are examples of osteogenic biomaterial strategies that involve the discussed calcium ion channels, calcium-dependent cellular structures, or calcium ion-regulating cellular features. Understanding the distinct ways calcium channels and signaling regulate these processes may uncover potential targets for advancing biomaterials with regenerative osteogenic capabilities.

Legal Penalties for Physicians Providing Gender-Affirming Care.

This Viewpoint explains the "legal limbo" physicians may find themselves in, straddling state laws banning gender-affirming care and federal nondiscrimination law, both of which remain unclear due to ongoing legal challenges in the courts.

Morphometric Analysis and Observer Perceptions Following Transvestibular Chondrolaryngoplasty.

OBJECTIVES: To assess novel morphometric measurement strategies and observer perception ratings as potential metrics for evaluating gender-affirming transvestibular chondrolaryngoplasty in reducing contour protrusion of the neck. METHODS: High-resolution preoperative and 3-month postoperative photographs of a pilot series of 10 patients (n = 10) who underwent endoscopic transvestibular chondrolaryngoplasty were collected. Morphometric measurements of "light reflex" and lateral view thyroid protrusion angles of the neck contours were analyzed. Pre- and postoperative photographs were presented in random order in a survey to 17 untrained judges and rated on perceived masculinity/femininity and thyroid notch protrusion on a 7-point scale. A pre- to postoperative change in morphometric angles and subjective ratings was assessed using paired t-tests and Wilcoxon signed-rank tests. RESULTS: Mean light reflex angles were reduced after surgery from 78.6° to 40.5° in the anterior neutral view (P = .0003), from 45.2° to 24.4° in the anterior extended view (P = .003), and from 7.03° to 4.32° in the lateral view (P = .006). Median survey ratings of neck photographs were improved after surgery, from 4 to 3 in gender perception toward more feminine perception (P < .0001) and from 4 to 2 in thyroid protrusion toward less protrusive perception (P < .0001). CONCLUSIONS: Morphometric analysis in anterior and lateral views as well as subjective gender perception and contour protrusion measures following feminization chondrolaryngoplasty by endoscopic transvestibular scarless approach demonstrate encouraging possibilities as outcome evaluation measures for chondrolaryngoplasty.

Association of Patient-Reported Anxiety and Pain After Alveolar Bone Grafting.

OBJECTIVE: To evaluate the role of psychosocial well-being on perioperative pain and opioid use among patients with cleft lip and palate (CLP) undergoing alveolar bone grafting (ABG). DESIGN: Retrospective review. SETTING: Tertiary level craniofacial clinic. PARTICIPANTS: 34 patients with CLP (median age: 11.7 years), including 25 (73.5%) unilateral CLP and 9 (26.5%) bilateral CLP, who underwent ABG from 2015 to 2022. INTERVENTIONS: ABG using iliac crest bone graft. Patients were prospectively administered four patient-reported psychosocial instruments from the Patient-Reported Outcomes Measurement Information System. MAIN OUTCOME MEASURES: Perioperative opioid use in morphine equivalent dosage/kilogram, patient-reported pain scores, and length of hospital stay after ABG. RESULTS: Patient-reported anxiety (r = 0.41, p = 0.02) and depressive symptoms (r = 0.35, p = 0.04) correlated to higher perioperative opioid usage. Multivariable regression models including psychosocial scores, total acetaminophen usage, length of surgery, and other simultaneous surgeries were developed for total opioid usage, patient-reported pain, and length of hospital stay. Patient-reported anxiety was independently predictive of higher perioperative opioid use (ß=0.36, p = 0.01) and higher pain scores (ß=0.39, p = 0.02), but not length of hospital stay. CONCLUSIONS: We identified an association for patient-reported anxiety and perioperative opioid use and pain in a CLP cohort undergoing ABG. Future considerations in preoperative patient and family consultation may be indicated in patients self-reporting higher anxiety in an effort to minimize perioperative opioid usage.

Modulating Temporospatial Phosphate Equilibrium by Nanoparticulate Mineralized Collagen Materials Induces Osteogenesis via PiT-1 and PiT-2.

The temporospatial equilibrium of phosphate contributes to physiological bone development and fracture healing, yet optimal control of phosphate content has not been explored in skeletal regenerative materials. Nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) is a synthetic, tunable material that promotes in vivo skull regeneration. In this work, the effects of MC-GAG phosphate content on the surrounding microenvironment and osteoprogenitor differentiation are investigated. This study finds that MC-GAG exhibits a temporal relationship with soluble phosphate with elution early in culture shifting to absorption with or without differentiating primary bone marrow-derived human mesenchymal stem cells (hMSCs). The intrinsic phosphate content of MC-GAG is sufficient to stimulate osteogenic differentiation of hMSCs in basal growth media without the addition of exogenous phosphate in a manner that can be severely reduced, but not eliminated, by knockdown of the sodium phosphate transporters PiT-1 or PiT-2. The contributions of PiT-1 and PiT-2 to MC-GAG-mediated osteogenesis are nonredundant but also nonadditive, suggestive that the heterodimeric form is essential to its activity. These findings indicate that the mineral content of MC-GAG alters phosphate concentrations within a local microenvironment resulting in osteogenic differentiation of progenitor cells via both PiT-1 and PiT-2.

Gender Affirming Surgery in Nonbinary Patients: A Single Institutional Experience.

Background An increasing number of nonbinary patients are receiving gender-affirming procedures due to improved access to care. However, the preferred treatments for nonbinary patients are underdescribed. The purpose of this study was to investigate the goals and treatments of nonbinary patients. Methods A retrospective study of patients who self-identified as nonbinary from our institutional Gender Health Program was conducted. Patient demographics, clinical characteristics, surgical goals, and operative variables were analyzed. Results Of the 375 patients with gender dysphoria, 67 (18%) were nonbinary. Over half of the nonbinary patients were assigned male at birth ( n = 57, 85%) and nearly half preferred the gender pronoun they/them/theirs ( n = 33, 49%). A total of 44 patients (66%) received hormone therapy for an average of 2.5 ± 3.6 years, primarily estrogen ( n = 39). Most patients ( n = 46, 69%) received or are interested in gender-affirming surgery, of which, almost half were previously on hormone therapy ( n = 32, 48%). The most common surgeries completed or desired were facial feminization surgery ( n = 15, 22%), vaginoplasty ( n = 15, 22%), mastectomy ( n = 11, 16%), and orchiectomy ( n = 9, 13%). Nonbinary patients who were assigned male at birth (NB-AMAB) were more often treated with hormones compared to nonbinary patients assigned female at birth (NB-AFAB) (72% vs. 30%, p = 0.010). Conversely, patients who were AFAB were more likely to complete or desire surgical intervention than those who were AMAB (100% vs. 63.0%, p < 0.021). Conclusion Majority of nonbinary patients were assigned male at birth. NB-AFAB patients all underwent surgical treatment, whereas NB-AMAB patients were predominantly treated with hormone therapy.

Effect of Gender-affirming Facial Feminization Surgery on Psychosocial Outcomes.

OBJECTIVE: This study investigates the effect of gender-affirming facial feminization surgery (FFS) on psychosocial outcomes in patients with gender dysphoria. BACKGROUND: Comprehensive analyses of psychosocial outcomes after gender-affirming FFS are absent in the literature resulting in a paucity of information on the impact of FFS on quality of life as well as ramifications in health insurance coverage of FFS. METHODS: Scores from 11 validated, quantitative instruments from the Patient-Reported Outcomes Measurement Information System (PROMIS) assessing anxiety, anger, depression, global mental health, global physical health, satisfaction with sex life, positive affect, emotional support, social isolation, companionship, and meaning and purpose. Patients within the preoperative group (pre-FFS) were evaluated >30 days before surgery and patients within the postoperative group (post-FFS) were evaluated ≥10 weeks after surgery. RESULTS: A total of 169 patients [mean (SD) age, 33.5 (10.8) years] were included. Compared with the pre-FFS group (n=107), the post-FFS group (n=62) reported improved scores anxiety (56.8±8.8 vs 60.1±7.9, P =0.01), anger (47.4±7.6 vs 51.2±9.6, P =0.01), depression (52.2±9.2 vs 57.0±8.9, P =0.001), positive affect (46.6±8.9 vs 42.9±8.7, P =0.01), meaning and purpose (49.9±10.7 vs 46.2±10.5, P =0.03), global mental health (46.7±7.6 vs 43.1±9.2, P =0.01), and social isolation (52.2±7.5 vs 55.4±7.4, P =0.01). Multivariable analysis to account for the effects of other gender-affirming surgeries, hormone therapy duration, preexisting mental health diagnoses, socioeconomic disparities, and patient-reported quality of social relationships on psychosocial functioning demonstrated that completion of FFS was independently predictive of improved scores. CONCLUSIONS: Gender-affirming FFS improves the quality of life by multiple psychosocial domains in transfeminine patients.