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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

Study designRetrospective cohort.ObjectiveTraumatic facial fractures (FFs) often require specialty consultation with Plastic Surgery (PS) or Otolaryngology (ENT); however, referral patterns are often non-standardized and institution specific. Therefore, we sought to compare management patterns and outcomes between PS and ENT, hypothesizing no difference in operative rates, complications, or mortality.MethodsWe performed a retrospective analysis of patients with FFs at a single Level I trauma center from 2014 to 2017. Patients were compared by consulting service: PS vs. ENT. Chi-square and Mann-Whitney-U tests were performed.ResultsOf the 755 patients with FFs, 378 were consulted by PS and 377 by ENT. There was no difference in demographic data (P > 0.05). Patients managed by ENT received a longer mean course of antibiotics (9.4 vs 7.0 days, P = 0.008) and had a lower rate of open reduction internal fixation (ORIF) (9.8% vs. 15.3%, P = 0.017), compared to PS patients. No difference was observed in overall operative rate (15.1% vs. 19.8%), use of computed tomography (CT) imaging (99% vs. 99%), time to surgery (65 vs. 55 hours, P = 0.198), length of stay (LOS) (4 vs. 4 days), 30-day complication rate (10.6% vs. 7.1%), or mortality (4.5% vs. 2.6%) (all P > 0.05).ConclusionOur study demonstrated similar baseline characteristics, operative rates, complications, and mortality between FFs patients who had consultation by ENT and PS. This supports the practice of allowing both ENT and PS to care for trauma FFs patients, as there appears to be similar standardized care and outcomes. Future studies are needed to evaluate the generalizability of our findings.

Facial feminization surgery (FFS) refers to a set of procedures aimed at altering the features of a masculine face to achieve a more feminine appearance. In the second part of this twopart series, assessment and operations involving the midface, mandible, and chin, as well as soft tissue modification of the nasolabial complex and chondrolaryngoplasty, are discussed. Finally, we provide a review of the literature on patient-reported outcomes in this population following FFS and suggest a path forward to optimize care for FFS patients.

Facial feminization surgery (FFS) incorporates aesthetic and craniofacial surgical principles and techniques to feminize masculine facial features and facilitate gender transitioning. A detailed understanding of the defining male and female facial characteristics is essential for success. In this first part of a two-part series, we discuss key aspects of the general preoperative consultation that should be considered when evaluating the prospective facial feminization patient. Assessment of the forehead, orbits, hairline, eyebrows, eyes, and nose and the associated procedures, including scalp advancement, supraorbital rim reduction, setback of the anterior table of the frontal sinus, rhinoplasty, and soft tissue modifications of the upper and midface are discussed. In the second part of this series, bony manipulation of the midface, mandible, and chin, as well as soft tissue modification of the nasolabial complex and chondrolaryngoplasty are discussed. Finally, a review of the literature on patient-reported outcomes in this population following FFS is provided.

The purpose of this study is twofold: (1) to determine the feasibility of optical coherence tomography (OCT) to differentiate normal and diseased tissue of the neck region intraoperatively and (2) to evaluate how accurately a cohort of test subjects can identify various tissue types when shown a sample set of OCT images. In this in vivo, prospective, single institutional study, an OCT imaging system (Niris, Imalux, Cleveland, OH) was used to image parathyroid, thyroid, lymph node, and fat tissue in 76 patients during neck surgery. Biopsies were performed for comparison of OCT images with histology in select cases (n = 20). Finally, a group of either surgeons or scientists familiar with OCT (n = 17) were shown a sample of OCT images and asked to identify the tissue. A total of 437 OCT images were analyzed, and characteristic features of each tissue type were identified. OCT demonstrated distinct differences in structural architecture and signal intensity that allows differentiation between thyroid and parathyroid tissues, lymph nodes, and fat. OCT images were also compared with histology with good correlation. There was no difference in correctly identifying OCT-imaged tissue type between surgeons and scientists. This study is the first in vivo OCT imaging study to evaluate both normal and diseased tissues that may be encountered during neck surgery. OCT has the potential to become a valuable intraoperative tool to differentiate diseased and normal thyroid tissue intraoperatively to obtain an "optical biopsy" in real time without fixation, staining, or tissue resection.

The ability of the extracellular matrix (ECM) to instruct progenitor cell differentiation has generated excitement for the development of materials-based regenerative solutions. Described a nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) material capable of inducing in vivo skull regeneration without exogenous growth factors or ex vivo progenitor cell-priming is described previously. Here, the contribution of titrating stiffness to osteogenicity is evaluated by comparing noncrosslinked (NX-MC) and crosslinked (MC) forms of MC-GAG. While both materials are osteogenic, MC demonstrates an increased expression of osteogenic markers and mineralization compared to NX-MC. Both materials are capable of autogenously activating the canonical BMPR signaling pathway with phosphorylation of Smad1/5. However, unlike NX-MC, human mesenchymal stem cells cultured on MC demonstrate significant elevations in the major mechanotransduction mediators YAP and TAZ expression, coincident with β-catenin activation in the canonical Wnt signaling pathway. Inhibition of YAP/TAZ activation reduces osteogenic expression, mineralization, and β-catenin activation in MC, with less of an effect on NX-MC. YAP/TAZ inhibition also results in a reciprocal increase in Smad1/5 phosphorylation and BMP2 expression. The results indicate that increasing MC-GAG stiffness induces osteogenic differentiation via the mechanotransduction mediators YAP/TAZ and the canonical Wnt signaling pathway, whereas the canonical BMPR signaling pathway is activated independent of stiffness.

Despite improved insurance coverage for gender confirmation surgeries in the United States, coverage for facial feminization surgery (FFS) continues to be difficult. Here, we describe our institutional experience on navigation, time, and costs of the FFS insurance authorization process.MethodsFFS consults (n = 40) at the University of California, Los Angeles (2018-2020) were reviewed for time and cost to definitive insurance authorization decision. Patients were stratified into 3 groups based on authorization process: Group A (standard approval, n = 26, 65.0%) including public and private insurances; Group B (extended approval, n = 10, 25.0%) consisting of private insurance plans that initially denied and required multi-level appeals for denial overturn; and Group C (denial, n = 4, 10.0%), including private insurance plans that denied even after multi-level appeals.ResultsAn estimated 90% of all patient consults were approved for FFS under insurance. Group A averaged 1.1 months for approval, requiring 1.4 hours of administrative time translating to $38.18 per patient. The addition of multi-level appeals in Groups B and C increased the total time for a definitive decision (7.0 and 5.1 months, respectively) and required both surgeon and administrative time to navigate the process (10.8 and 12.0 hours, respectively). The time spent on the presurgical authorization process for Groups B and C translated to an over 20-fold increase in cost ($855.00 and $988.38, respectively) compared with Group A.ConclusionNavigation of the insurance process for FFS is challenging and time-consuming; however, coverage is a reality in California provided that multi-level appeals are exhausted.

Osseous work in facial feminization has been largely developed by comparing the qualitative and quantitative anthropometric differences between male and female cadaveric skulls. While virtual surgical planning has allowed for improved accuracy and ease in osteotomies and recontouring procedures in facial feminization, ultimately, a subjective decision-making process is still required. In this work, we describe a novel method of simplifying facial feminization by virtually modeling all osseous surgical maneuvers for facial feminization with a reference female skull.

BackgroundThe role of surgical reconstruction following melanoma extirpation is well recognized. Although technical considerations depend on patient anatomy and surgeon preference, the optimal timing of reconstruction remains unclear. This study aims to evaluate clinical and oncologic outcomes in melanoma extirpation followed by immediate reconstruction.MethodsWe retrospectively identified patients who underwent immediate reconstruction following head and neck melanoma excision at our institution between January 2013 and December 2016. Demographic and clinical characteristics, operative variables, and outcome data were extracted.ResultsOverall, 197 patients (male 70.6%) underwent excision followed by immediate reconstruction. Of the 70 patients with a history of cutaneous malignancy, 46 (65.7%) had a prior melanoma and 26 (37.1%) had 2 or more types of skin cancers. Of the 202 lesions resected, 138 (68.3%) were invasive, whereas 64 (31.7%) were in situ. The most frequent anatomic location involved was the cheek (34.2%), followed by scalp (31.2%). Reconstruction technique varied, with 116 (57.4%) lesions repaired by adjacent tissue transfer, 24 (11.9%) by full-thickness skin graft, 23 (11.4%) by complex primary closure, 17 (8.4%) by split-thickness skin graft, and 22 (10.9%) by more than 1 technique. On postoperative pathologic assessment, 2 patients had positive margins and 5 experienced local recurrence (mean follow-up: 2.3 years). In an unadjusted bivariate analysis, history of melanoma (P = 0.015) was significantly associated with local recurrence.ConclusionsReconstruction at time of excision is an oncologically safe approach for the management of patients with malignant melanoma. A prior history of melanoma may be associated with local recurrence.

Taste bud cell differentiation is extremely important for taste sensation. Immature taste bud cells cannot function during taste perception transmission to the nerve. In this study, we investigated whether hedgehog signaling affected taste bud cell differentiation and whether transient receptor potential vanilloid 1 (TRPV1) played a key role in dry mouth. The induction of dry mouth due to salivary gland resection (SGR) was confirmed on the basis of reduced salivation and disrupted fungiform papillae. The expression of keratin 8 (K8) of taste bud cells, neurofilament (NF), sonic hedgehog (Shh), and glioma-associated oncogene homolog 1 (Gli1) around taste bud cells was downregulated; however, the expression of TRPV1, P2X purinoceptor 3 (P2X3), and hematopoietic stem cell factor (c-Kit) was upregulated at the NF ends in the dry mouth group. To investigate the effect of TRPV1 defect on dry mouth, we induced dry mouth in the TRPV-/- group. The K8, NF, and P2X3 expression patterns were the same in the TRPV1 wild-type and TRPV1-/- dry mouth groups. However, Shh and c-Kit expression decreased regardless of dry mouth in the case of TRPV1 deficiency. These results indicated that TRPV1 positively regulated proliferation during taste bud cell injury by blocking the Shh/Gli1 pathway. In addition, not only cell proliferation but also differentiation of taste bud cells could not be regulated under TRPV1-deficiency conditions. Thus, TRPV1 positively regulates taste bud cell innervation and differentiation; this finding could be valuable in the clinical treatment of dry mouth-related taste dysfunction. [ABSTRACT FROM AUTHOR]

The application of next-generation sequencing in research and particularly in clinical routine requires highly accurate variant calling. Here we describe UVC, a method for calling small variants of germline or somatic origin. By unifying opposite assumptions with sublation, we discovered the following two empirical laws to improve variant calling: allele fraction at high sequencing depth is inversely proportional to the cubic root of variant-calling error rate, and odds ratios adjusted with Bayes factors can model various sequencing biases. UVC outperformed other variant callers on the GIAB germline truth sets, 192 scenarios of in silico mixtures simulating 192 combinations of tumor/normal sequencing depths and tumor/normal purities, the GIAB somatic truth sets derived from physical mixture, and the SEQC2 somatic reference sets derived from the breast-cancer cell-line HCC1395. UVC achieved 100% concordance with the manual review conducted by multiple independent researchers on a Qiagen 71-gene-panel dataset derived from 16 patients with colon adenoma. UVC outperformed other unique molecular identifier (UMI)-aware variant callers on the datasets used for publishing these variant callers. Performance was measured with sensitivity-specificity trade off for called variants. The improved variant calls generated by UVC from previously published UMI-based sequencing data provided additional insight about DNA damage repair. UVC is open-sourced under the BSD 3-Clause license at https://github.com/genetronhealth/uvc and quay.io/genetronhealth/gcc-6-3-0-uvc-0-6-0-441a694 [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: The objective of this study were to determine if any of the 10 attributes of the standardized letter of recommendation (SLOR) correlate significantly with objective measures of each applicant and to determine whether professor characteristics were associated with reported SLOR attributes.Study Design: Retrospective cohort study.Methods: We reviewed 339 SLORs from 187 otolaryngology residency applicants. The 10 SLOR attributes were converted into a percentile score and statistically analyzed.Results: All 10 SLOR attributes had a mean ± standard deviation above the 80th percentile (0.82-0.93 ± 0.08-0.52) and negative skewness. United States Medical Licensing Examination step 1 and 2 scores correlated most strongly with match potential (B = 93.1,P < .001 and B = 96.3, P = .002, respectively). Students from top 40 National Institutes of Health-funded institutions had a significant difference in length of relationship with their letter writer (B = -0.51, P = .02) and interpersonal communication skills (B = -12.9, P = .011). Alpha Omega Alpha (AOA) and non-AOA members differed in medical knowledge (B = 21.0, P = .007), research (B = -8.80, P = .036), and commitment to otolaryngology (B = -25.89, P = .020). Total number of research experiences correlated most strongly with medical knowledge (B = -16.55, P = .011). There was a significant difference in means between length of relationship and professorial rank (F[4, 339] = 3.61, P = .023), administrative position (F[5, 339] = 5.43, P = .002), and institution of the letter writer (P < .001).Conclusions: Overall, the lack of correlation between SLOR attributes and objective measures suggests that the SLOR adds little to the residency application. Professor characteristics were similarly not associated with any of the 10 SLOR attributes; however, there were significant differences in the length of relationship between the professor and students with respect to professor rank, administrative rank, and institution of the letter writer.Level Of Evidence: NA Laryngoscope, 130:603-608, 2020. [ABSTRACT FROM AUTHOR]