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OBJECTIVE: To understand psychosocial functioning before and after gender-affirming facial feminization surgery (FFS) as well as identify predictors of postoperative psychosocial functioning. SUMMARY BACKGROUND DATA: Few investigations have rigorously explored the impact of gender-affirming FFS on psychosocial functioning in transgender and gender non-binary (TGNB) individuals. This knowledge gap hinders the identification of methods to optimize mental health quality-of-life outcomes after FFS and carries repercussions for access to care. METHODS: Adult TGNB participants awaiting gender-affirming FFS were prospectively enrolled and administered Patient-Reported Outcomes Measurement Information System (PROMIS) instruments assessing anxiety, anger, depression, global mental and physical health, positive affect, emotional support, social isolation, companionship, and meaning and purpose before and 3-6 months after FFS. Paired t-tests compared pre- and postoperative scores. Multivariable linear models identified predictors of postoperative psychosocial outcomes. RESULTS: Among the domains, psychosocial scores improved for anxiety, depression, global mental health, social isolation, and positive affect after FFS. When accounting for potential variables contributing to postoperative psychosocial scores including other gender-affirming surgeries, hormone therapy duration, and private versus public insurance type, we found that preoperative depression scores independently predicted the variance in all other postoperative scores with global mental health (ß=-0.52, 95%CI -0.58--0.31 P<0.001), anxiety (ß=0.40, 95% CI 0.21-0.51, P<0.001), and meaning and purpose (ß=-0.52, 95% CI -0.78--0.42 P<0.001) as the strongest models. CONCLUSIONS: This study suggests that gender-affirming FFS improves psychosocial functioning; however, such improvements are highly influenced by the baseline psychological functioning of each individual. These findings indicate that preoperative psychological functioning may be a potential avenue for improving outcomes after FFS via perioperative psychological interventions.
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SUMMARY: The increase in access to facial gender-affirming surgery has resulted in a rise in facial feminization surgeries for transfeminine and gender non-binary populations. However, refined execution of facial masculinization is challenged by the lack of defined measurements for facial augmentation, the lack of long-term predictability in autologous bone grafting in augmentation procedures, and the lack of precision in traditional facial augmentation procedures with generic alloplastic implants. In this work, we describe an innovation in facial masculinization surgery using modern reconstructive craniofacial surgical techniques with preoperative virtual modeling and the fabrication of three-dimensionally printed, patient-specific custom implants.
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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.
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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.
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Cara , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Adulto , Cara/anatomía & histología , Cara/diagnóstico por imagen , Cara/cirugía , Cirugía de Reasignación de Sexo/métodos , Etnicidad , Personas Transgénero , Antropometría/métodos , Estudios RetrospectivosRESUMEN
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.
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Personas Transgénero , Transexualidad , Humanos , Estados Unidos , Atención de Afirmación de Género , Identidad de Género , Política de SaludRESUMEN
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.
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Labio Leporino , Fisura del Paladar , Apnea Obstructiva del Sueño , Insuficiencia Velofaríngea , Humanos , Fisura del Paladar/complicaciones , Fisura del Paladar/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Faringe/cirugía , Insuficiencia Velofaríngea/etiología , Insuficiencia Velofaríngea/cirugía , Apnea Obstructiva del Sueño/etiología , Apnea Obstructiva del Sueño/cirugíaRESUMEN
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.
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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.
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Recently, growing evidence of the relationship between G-protein coupled receptor 44 (GPR44) and the inflammation-cancer system has garnered tremendous interest, while the exact role of GPR44 has not been fully elucidated. Currently, there is a strong and urgent need for the development of non-invasive in vivo GPR44 positron emission tomography (PET) radiotracers that can be used to aid the exploration of the relationship between inflammation and tumor biologic behavior. Accordingly, the choosing and radiolabeling of existing GPR44 antagonists containing a fluorine group could serve as a viable method to accelerate PET tracers development for in vivo imaging to this purpose. The present study aims to evaluate published (2000-present) indole-based and cyclopentenyl-indole-based analogues of the GPR44 antagonist to guide the development of fluorine-18 labeled PET tracers that can accurately detect inflammatory processes. The selected analogues contained a crucial fluorine nuclide and were characterized for various properties including binding affinity, selectivity, and pharmacokinetic and metabolic profile. Overall, 26 compounds with favorable to strong binding properties were identified. This review highlights the potential of GPR44 analogues for the development of PET tracers to study inflammation and cancer development and ultimately guide the development of targeted clinical therapies.
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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.
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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.
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Analgésicos Opioides , Recuperación Mejorada Después de la Cirugía , Masculino , Humanos , Analgésicos Opioides/uso terapéutico , Tiempo de Internación , Estudios Retrospectivos , Feminización/tratamiento farmacológico , Morfina , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/diagnósticoRESUMEN
The regulation of bile acid pathways has become a particularly promising therapeutic strategy for a variety of metabolic disorders, cancers, and diseases. However, the hydrophobicity of bile acids has been an obstacle to clinical efficacy due to off-target effects from rapid drug absorption. In this report, we explored a novel strategy to design new structure fragments based on lithocholic acid (LCA) with improved hydrophilicity by introducing a polar "oxygen atom" into the side chain of LCA, then (i) either retaining the carboxylic acid group or replacing the carboxylic acid group with (ii) a diol group or (iii) a vinyl group. These novel fragments were evaluated using luciferase-based reporter assays and the MTS assay. Compared to LCA, the result revealed that the two lead compounds 1a-1b were well tolerated in vitro, maintaining similar potency and efficacy to LCA. The MTS assay results indicated that cell viability was not affected by dose dependence (under 25 µM). Additionally, computational model analysis demonstrated that compounds 1a-1b formed more extensive hydrogen bond networks with Takeda G protein-coupled receptor 5 (TGR5) than LCA. This strategy displayed a potential approach to explore the development of novel endogenous bile acids fragments. Further evaluation on the biological activities of the two lead compounds is ongoing.
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Ácidos y Sales Biliares , Ácido Litocólico , Ácido Litocólico/farmacología , Ácidos y Sales Biliares/farmacologíaRESUMEN
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.
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Custom synthesis of extracellular matrix (ECM)-inspired materials for condition-specific reconstruction has emerged as a potentially translatable regenerative strategy. In skull defect reconstruction, nanoparticulate mineralized collagen glycosaminoglycan scaffolds (MC-GAG) have demonstrated osteogenic and anti-osteoclastogenic properties, culminating in the ability to partially heal in vivo skull defects without the addition of exogenous growth factors or progenitor cell loading. In an effort to reduce catabolism during early skull regeneration, we fabricated a composite material (MCGO) of MC-GAG and recombinant osteoprotegerin (OPG), an endogenous anti-osteoclastogenic decoy receptor. In the presence of differentiating osteoprogenitors, MCGO demonstrated an additive effect with endogenous OPG limited to the first 14 days of culture with total eluted and scaffold-bound OPG exceeding that of MC-GAG. Functionally, MCGO exhibited similar osteogenic properties as MC-GAG, however, MCGO significantly reduced maturation and resorptive activities of primary human osteoclasts. In a rabbit skull defect model, MCGO scaffold-reconstructed defects displayed higher mineralization as well as increased hardness and microfracture resistance compared to non-OPG functionalized MC-GAG scaffolds. The current work suggests that MCGO is a development in the goal of reaching a materials-based strategy for skull regeneration.