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.

Delaying Suspension Syndrome Onset in Aerially Suspended Victims Through Leg Raising.

INTRODUCTION: Suspension syndrome (SS) develops when venous blood pools in extremities of passively suspended individuals, resulting in presyncopal symptoms and potential unconsciousness or death independent of additional injuries. We investigated use of leg raising to delay onset of SS, as it can decrease venous pooling and increase cardiac return and systemic perfusion. METHODS: Participants were suspended in rock climbing harnesses at an indoor climbing wall in a legs-dangling control position or a legs-raised interventional position to compare physiological outcomes between groups. Participants were suspended for a maximum of 45 min. Onset of 2 or more symptoms of SS, such as vertigo, lightheadedness, or nausea, halted suspension immediately. We recorded each participant's heart rate, blood pressure, oxygen saturation, lower leg oxygen saturation, pain rating, and presyncope scores presuspension, midsuspension, and postsuspension, as well as total time suspended. RESULTS: There were 24 participants. There was a significant difference in total time suspended between groups (43.05±6.7 min vs 33.35±9.02 min, p=0.007). There was a significant difference in heart rate between groups overall (p=0.012), and between groups, specifically at the midsuspension time interval (80±11 bpm vs 100±17 bpm, p=0.003). Pain rating was significantly different between groups (p=0.05). Differences in blood pressure, oxygen saturation, lower leg oxygen saturation, and presyncope scores were not significant. CONCLUSION: Leg raising lengthened the time individuals tolerated passive suspension and delayed symptom onset.

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.

Student advanced trauma management and skills (SATMAS): a validation study.

INTRODUCTION: Despite trauma accounting 9% of global mortality, it has been demonstrated that undergraduate trauma teaching is inadequate nationally and worldwide. With COVID-19 exacerbating this situation, a scalable, accessible, and cost-effective undergraduate trauma teaching is required. METHODS: Our Continual Professional Development United Kingdom (CPUDK)-accredited University Hospitals Birmingham (UHB) Major Trauma Service (MTS) affiliated programme consisted of seven biweekly pre-recorded sessions that were delivered online through the Moodle educational platform to University of Birmingham students. Pre- and post-randomised session-specific multiple-choice questions (MCQs) and anonymous feedback forms were administered. RESULTS: There were 489 student responses, with 63 students completing all seven sessions. On an 8-point scale, students' objective knowledge scores increased by a mean of 1.2 (p < 0.001). Using a 5-point Likert scale, students also showed improvement in subjective outcomes including their confidence in assessing trauma patient (absolute difference (AD) 1.38, p < 0.001), advising initial investigations and formulating initial management plans (AD 1.78, p < 0.001) and thereby their confidence to manage a trauma patient overall (AD 1.98, p < 0.001). A total of 410 student responses endorsed the online delivery of SATMAS through Moodle and recommended SATMAS to future medical students. CONCLUSION: SATMAS has demonstrated positive student feedback and extensive recruitment from only one centre, demonstrating that our programme can be an indispensable low-cost learning resource that prepares undergraduate medical students for their trauma exams and informs the implementation of clinical skills required by all doctors. We publish our pilot study findings to encourage similar teaching programmes to be adopted at other universities nationally and internationally, to synergistically benefit students, tutors, and ultimately patients, on a larger scale.

Transcriptomic signatures of individual cell types in cerebral cavernous malformation.

Cerebral cavernous malformation (CCM) is a hemorrhagic neurovascular disease with no currently available therapeutics. Prior evidence suggests that different cell types may play a role in CCM pathogenesis. The contribution of each cell type to the dysfunctional cellular crosstalk remains unclear. Herein, RNA-seq was performed on fluorescence-activated cell sorted endothelial cells (ECs), pericytes, and neuroglia from CCM lesions and non-lesional brain tissue controls. Differentially Expressed Gene (DEG), pathway and Ligand-Receptor (LR) analyses were performed to characterize the dysfunctional genes of respective cell types within CCMs. Common DEGs among all three cell types were related to inflammation and endothelial-to-mesenchymal transition (EndMT). DEG and pathway analyses supported a role of lesional ECs in dysregulated angiogenesis and increased permeability. VEGFA was particularly upregulated in pericytes. Further pathway and LR analyses identified vascular endothelial growth factor A/ vascular endothelial growth factor receptor 2 signaling in lesional ECs and pericytes that would result in increased angiogenesis. Moreover, lesional pericytes and neuroglia predominantly showed DEGs and pathways mediating the immune response. Further analyses of cell specific gene alterations in CCM endorsed potential contribution to EndMT, coagulation, and a hypoxic microenvironment. Taken together, these findings motivate mechanistic hypotheses regarding non-endothelial contributions to lesion pathobiology and may lead to novel therapeutic targets. Video Abstract.

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.

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 .

Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part I: Event Rates and Clinical Outcome.

BACKGROUND: Cerebral cavernous malformation with symptomatic hemorrhage (SH) are targets for novel therapies. A multisite trial-readiness project (https://www.clinicaltrials.gov; Unique identifier: NCT03652181) aimed to identify clinical, imaging, and functional changes in these patients. METHODS: We enrolled adult cerebral cavernous malformation patients from 5 high-volume centers with SH within the prior year and no planned surgery. In addition to clinical and imaging review, we assessed baseline, 1- and 2-year National Institutes of Health Stroke Scale, modified Rankin Scale, European Quality of Life 5D-3 L, and patient-reported outcome-measurement information system, Version 2.0. SH and asymptomatic change rates were adjudicated. Changes in functional scores were assessed as a marker for hemorrhage. RESULTS: One hundred twenty-three, 102, and 69 patients completed baseline, 1- and 2-year clinical assessments, respectively. There were 21 SH during 178.3 patient years of follow-up (11.8% per patient year). At baseline, 62.6% and 95.1% of patients had a modified Rankin Scale score of 1 and National Institutes of Health Stroke Scale score of 0 to 4, respectively, which improved to 75.4% (P=0.03) and 100% (P=0.06) at 2 years. At baseline, 74.8% had at least one abnormal patient-reported outcome-measurement information system, Version 2.0 domain compared with 61.2% at 2 years (P=0.004). The most common abnormal European Quality of Life 5D-3 L domains were pain (48.7%), anxiety (41.5%), and participation in usual activities (41.4%). Patients with prospective SH were more likely than those without SH to display functional decline in sleep, fatigue, and social function patient-reported outcome-measurement information system, Version 2.0 domains at 2 years. Other score changes did not differ significantly between groups at 2 years. The sensitivity of scores as an SH marker remained poor at the time interval assessed. CONCLUSIONS: We report SH rate, functional, and patient-reported outcomes in trial-eligible cerebral cavernous malformation with SH patients. Functional outcomes and patient-reported outcomes generally improved over 2 years. No score change was highly sensitive or specific for SH and could not be used as a primary end point in a trial.

Generating a multimodal artificial intelligence model to differentiate benign and malignant follicular neoplasms of the thyroid: A proof-of-concept study.

BACKGROUND: Machine learning has been increasingly used to develop algorithms that can improve medical diagnostics and prognostication and has shown promise in improving the classification of thyroid ultrasound images. This proof-of-concept study aims to develop a multimodal machine-learning model to classify follicular carcinoma from adenoma. METHODS: This is a retrospective study of patients with follicular adenoma or carcinoma at a single institution between 2010 and 2022. Demographics, imaging, and perioperative variables were collected. The region of interest was annotated on ultrasound and used to perform radiomics analysis. Imaging features and clinical variables were then used to create a random forest classifier to predict malignancy. Leave-one-out cross-validation was conducted to evaluate classifier performance using the area under the receiver operating characteristic curve. RESULTS: Patients with follicular adenomas (n = 7) and carcinomas (n = 11) with complete imaging and perioperative data were included. A total of 910 features were extracted from each image. The t-distributed stochastic neighbor embedding method reduced the dimension to 2 primary represented components. The random forest classifier achieved an area under the receiver operating characteristic curve of 0.76 (clinical only), 0.29 (image only), and 0.79 (multimodal data). CONCLUSION: Our multimodal machine learning model demonstrates promising results in classifying follicular carcinoma from adenoma. This approach can potentially be applied in future studies to generate models for preoperative differentiation of follicular thyroid neoplasms.

Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part II: Biomarkers and Trial Modeling.

BACKGROUND: Quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative perfusion (DCEQP) magnetic resonance imaging sequences assessing iron deposition and vascular permeability were previously correlated with new hemorrhage in cerebral cavernous malformations. We assessed their prospective changes in a multisite trial-readiness project. METHODS: Patients with cavernous malformation and symptomatic hemorrhage (SH) in the prior year, without prior or planned lesion resection or irradiation were enrolled. Mean QSM and DCEQP of the SH lesion were acquired at baseline and at 1- and 2-year follow-ups. Sensitivity and specificity of biomarker changes were analyzed in relation to predefined criteria for recurrent SH or asymptomatic change. Sample size calculations for hypothesized therapeutic effects were conducted. RESULTS: We logged 143 QSM and 130 DCEQP paired annual assessments. Annual QSM change was greater in cases with SH than in cases without SH (P=0.019). Annual QSM increase by ≥6% occurred in 7 of 7 cases (100%) with recurrent SH and in 7 of 10 cases (70%) with asymptomatic change during the same epoch and 3.82× more frequently than clinical events. DCEQP change had lower sensitivity for SH and asymptomatic change than QSM change and greater variance. A trial with the smallest sample size would detect a 30% difference in QSM annual change during 2 years of follow-up in 34 or 42 subjects (1 and 2 tailed, respectively); power, 0.8, α=0.05. CONCLUSIONS: Assessment of QSM change is feasible and sensitive to recurrent bleeding in cavernous malformations. Evaluation of an intervention on QSM percent change may be used as a time-averaged difference between 2 arms using a repeated measures analysis. DCEQP change is associated with lesser sensitivity and higher variability than QSM. These results are the basis of an application for certification by the US Food and Drug Administration of QSM as a biomarker of drug effect on bleeding in cavernous malformations. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03652181.

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.

Benign and Malignant Ovarian Teratomas: Multimodality Imaging Findings With Histopathologic Correlation.

ABSTRACT: The purpose of this article is to provide a comprehensive review of the imaging findings along with histopathologic correlation of mature (benign) teratomas and malignant ovarian teratomas, which include both immature teratomas and malignant degeneration of mature teratomas. The radiologist's ability to provide an accurate diagnosis plays an essential role in guiding the interdisciplinary care of patients with malignant teratomas and improving their outcomes.

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.

Reanalysis of primate brain circadian transcriptomics reveals connectivity-related oscillations.

Research shows that brain circuits controlling vital physiological processes are closely linked with endogenous time-keeping systems. In this study, we aimed to examine oscillatory gene expression patterns of well-characterized neuronal circuits by reanalyzing publicly available transcriptomic data from a spatiotemporal gene expression atlas of a non-human primate. Unexpectedly, brain structures known for regulating circadian processes (e.g., hypothalamic nuclei) did not exhibit robust cycling expression. In contrast, basal ganglia nuclei, not typically associated with circadian physiology, displayed the most dynamic cycling behavior of its genes marked by sharp temporally defined expression peaks. Intriguingly, the mammillary bodies, considered hypothalamic nuclei, exhibited gene expression patterns resembling the basal ganglia, prompting reevaluation of their classification. Our results emphasize the potential for high throughput circadian gene expression analysis to deepen our understanding of the functional synchronization across brain structures that influence physiological processes and resulting complex behaviors.

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.

The induction of p53 correlates with defects in the production, but not the levels, of the small ribosomal subunit and stalled large ribosomal subunit biogenesis.

Ribosome biogenesis is one of the biggest consumers of cellular energy. More than 20 genetic diseases (ribosomopathies) and multiple cancers arise from defects in the production of the 40S (SSU) and 60S (LSU) ribosomal subunits. Defects in the production of either the SSU or LSU result in p53 induction through the accumulation of the 5S RNP, an LSU assembly intermediate. While the mechanism is understood for the LSU, it is still unclear how SSU production defects induce p53 through the 5S RNP since the production of the two subunits is believed to be uncoupled. Here, we examined the response to SSU production defects to understand how this leads to the activation of p53 via the 5S RNP. We found that p53 activation occurs rapidly after SSU production is blocked, prior to changes in mature ribosomal RNA (rRNA) levels but correlated with early, middle and late SSU pre-rRNA processing defects. Furthermore, both nucleolar/nuclear LSU maturation, in particular late stages in 5.8S rRNA processing, and pre-LSU export were affected by SSU production defects. We have therefore uncovered a novel connection between the SSU and LSU production pathways in human cells, which explains how p53 is induced in response to SSU production defects.

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.