Faculty Bibliography

BACKGROUND:Sexually transmitted infections (STIs) following penile reconstruction in transgender, nonbinary, and other gender expansive (T/GE) populations has not previously been described, despite known risk factors in the population. Following T/GE penile reconstruction, care providers may underdiagnose STI without anatomically appropriate guidelines. METHODS:A detailed anonymous online survey of experiences of T/GE penile reconstruction patients was constructed with community input. Respondents were recruited from online support groups. RESULTS:128 T/GE people with experience of penile reconstruction responded to an anonymous survey posted in online support groups January to May 2020. Seven respondents (5.5%) self-reported one or more of the listed STIs at any point after penile reconstruction. All respondents with neourethras were diagnosed with localized STIs in nonurethral (extrapenile) locations only, and lack of vaginectomy was correlated with STI (p = 0.002). STIs were correlated with reporting sex with cisgender men (p = 0.001), transgender men (p = 0.009), and transgender women (p = 0.012). Of healthcare access variables, only receiving healthcare at a Community Health Center was correlated with STI history (p = 0.003). CONCLUSION/CONCLUSIONS:This exploratory survey indicates STI occurs after penile reconstruction in T/GE patients. Clinical confirmation is needed to identify specific risk factors and relative susceptibility of post-reconstruction anatomy to STIs. Given no previous surveillance recommendations for this population and the correlation of healthcare provider location with STI prevalence, underdiagnoses are likely. Based on the authors' clinical experience, we describe a urogenital screening algorithm following gender affirming penile reconstruction.

BACKGROUND:Facial feminization surgery is composed of a variety of craniomaxillofacial surgical procedures that are increasingly sought after by male-to-female transgender patients and by those seeking feminization of the face. Facial feminization surgery can play a prominent role in alleviating gender dysphoria. In consideration of an observed increase in gender-affirming procedures performed in recent years, a broad knowledge base in the techniques, outcomes, and challenges of facial feminization surgery should be established by surgeons offering these procedures. Our review was designed to critically appraise the current literature and inform future advancements in gender-affirming surgical practice. In addition, we detail a representative case to illustrate the senior author's approach to full facial feminization. METHODS:A comprehensive literature search of the PubMed, EMBASE, and Cochrane databases was conducted for studies published through June 2020 using following the search terms: "Face" OR "facial" OR "craniofacial" AND "Feminization" OR "Feminization Surgery" OR "Gender Reassignment" OR "Gender Affirming Surgery" OR "Gender Confirmation Surgery." Data on procedures, outcomes, patient age, follow-up time, complications, and patient satisfaction were collected. The data were categorized by facial thirds and then further stratified by facial feature. RESULTS:Our search yielded 388 articles. Thirty articles fit our inclusion criteria, and of these, 23 articles were included in the review. We extracted primary data pertaining to 3554 patients with an age range of 18 to 73 who underwent 8506 total procedures. Most of the procedures addressed the upper facial third (hairline, forehead, and brow), comprising 49.1% of total procedures performed. Further categorization by facial feature revealed that the most commonly addressed feature was the forehead (34.6% of procedures), followed by the nose (12.8%) and the chin (12.2%). In studies that used quantitative measures to gauge patient-reported outcomes, satisfaction was high. CONCLUSIONS:Facial feminization surgery seems to be safe, whether it is conducted in a single stage or as a staged procedure. Patients report high satisfaction and better gender congruency after facial feminization procedures. Further research is needed to establish best surgical practice and gauge patient satisfaction beyond the length of average follow-up and determine the frequency with which adjunctive procedures are sought out.

Efficacy of monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor (calcitonin receptor-like receptor/receptor activity modifying protein-1, CLR/RAMP1) implicates peripherally-released CGRP in migraine pain. However, the site and mechanism of CGRP-evoked peripheral pain remain unclear. By cell-selective RAMP1 gene deletion, we reveal that CGRP released from mouse cutaneous trigeminal fibers targets CLR/RAMP1 on surrounding Schwann cells to evoke periorbital mechanical allodynia. CLR/RAMP1 activation in human and mouse Schwann cells generates long-lasting signals from endosomes that evoke cAMP-dependent formation of NO. NO, by gating Schwann cell transient receptor potential ankyrin 1 (TRPA1), releases ROS, which in a feed-forward manner sustain allodynia via nociceptor TRPA1. When encapsulated into nanoparticles that release cargo in acidified endosomes, a CLR/RAMP1 antagonist provides superior inhibition of CGRP signaling and allodynia in mice. Our data suggest that the CGRP-mediated neuronal/Schwann cell pathway mediates allodynia associated with neurogenic inflammation, contributing to the algesic action of CGRP in mice.

G protein-coupled receptors (GPCRs) regulate many pathophysiological processes and are major therapeutic targets. The impact of disease on the subcellular distribution and function of GPCRs is poorly understood. We investigated trafficking and signaling of protease-activated receptor 2 (PAR₂) in colitis. To localize PAR₂ and assess redistribution during disease, we generated knockin mice expressing PAR₂ fused to monomeric ultrastable green fluorescent protein (muGFP). PAR₂-muGFP signaled and trafficked normally. PAR₂ messenger RNA was detected at similar levels in Par₂-mugfp and wild-type mice. Immunostaining with a GFP antibody and RNAScope in situ hybridization using F2rl1 (PAR₂) and Gfp probes revealed that PAR₂-muGFP was expressed in epithelial cells of the small and large intestine and in subsets of enteric and dorsal root ganglia neurons. In healthy mice, PAR₂-muGFP was prominently localized to the basolateral membrane of colonocytes. In mice with colitis, PAR₂-muGFP was depleted from the plasma membrane of colonocytes and redistributed to early endosomes, consistent with generation of proinflammatory proteases that activate PAR₂ PAR₂ agonists stimulated endocytosis of PAR₂ and recruitment of Gα_q, Gα_i, and β-arrestin to early endosomes of T84 colon carcinoma cells. PAR₂ agonists increased paracellular permeability of colonic epithelial cells, induced colonic inflammation and hyperalgesia in mice, and stimulated proinflammatory cytokine release from segments of human colon. Knockdown of dynamin-2 (Dnm2), the major colonocyte isoform, and Dnm inhibition attenuated PAR₂ endocytosis, signaling complex assembly and colonic inflammation and hyperalgesia. Thus, PAR₂ endocytosis sustains protease-evoked inflammation and nociception and PAR₂ in endosomes is a potential therapeutic target for colitis.

OBJECTIVE:To describe the authors' experience diagnosing and managing intra-abdominal complications following robotic peritoneal flap vaginoplasty. The peritoneal flap vaginoplasty is a technique used to achieve consistent vaginal depth regardless of available natal tissue. Intra-abdominal complications following robotic peritoneal flap creation are rare but prompt diagnosis and management is critical to preventing patient harm. Given the infancy of the technique there is limited data on associated complications and their management. METHODS:Retrospective chart review identified patients undergoing robotically assisted peritoneal flap vaginoplasty by the senior authors between 2017 and 2020 who subsequently developed intra-abdominal complications requiring readmission and/or return to the operating room. Patient charts were analyzed for preoperative demographics, medical comorbidities, intraoperative details, postoperative complication presentation, diagnosis, management, and long-term outcomes. RESULTS:Out of 274 patients undergoing peritoneal flap vaginoplasty during the study period, six patients were identified who developed intra-abdominal complications (2.2%). One patient developed a postoperative hematoma requiring return to the operating room for diagnostic laparoscopy and hematoma evacuation. Two patients developed intraabdominal abscesses requiring diagnostic laparoscopy and abscess drainage. One patient developed recurrent episodes of small bowel obstructions that resolved with bowel rest. Two patients developed incarcerated internal hernias requiring diagnostic laparoscopy and internal hernia reduction. In one case, the hernia occurred at the peritoneal flap closure site, and in the other case the hernia occurred at the peritoneal flap donor site. CONCLUSIONS:Intra-abdominal complications following robot assisted peritoneal flap vaginoplasty are rare.  In addition to hematoma and abscess, small bowel incarceration and internal hernias are potential complications of peritoneal flap vaginoplasty that require prompt attention.

SUMMARY/CONCLUSIONS:As the field of plastic surgery continues to advance, so too do the number and complexity of ethical challenges faced by plastic surgeons. There is a paucity of literature, however, focusing on ethics in plastic surgery. Therefore, the authors offer a timely special topic series discussing ethical issues relevant to the field of plastic surgery. The goals of this series are four-fold: (1) to increase awareness of both frequently and less commonly encountered ethical issues in plastic surgery, (2) to foster discussion and debate of relevant and significant ethical issues, (3) to facilitate clinical ethics education and scholarship in plastic surgery, and (4) to apply an understanding and analysis of ethical issues in a way that optimizes clinical decision-making and delivery of patient care. In this introductory article, the authors discuss the current state of medical ethics scholarship in plastic surgery and introduce the first of several topics that will be detailed in the series. Ultimately, the hope is that increased awareness of the ethical challenges faced by surgeons and patients will improve the practice of plastic surgery.

BACKGROUND:In 1968, Ralph Millard published his "Millard II" method for repair of wide, complete unilateral cleft lip and nose deformity. In 1979, Murawski published a major modification of the Millard II procedure in Polish. This motif was taken up 8 years later by Mohler and 22 years later by Cutting. The Murawski variation on the Millard II procedure has become a dominant motif in unilateral cleft lip repair worldwide. This brief report intends to introduce the method to the English language literature and present long-term results. METHODS:The Murawski method alters the Millard II procedure by changing the upper medial curve into a point in the columellar base. This creates a broad C flap used to fill the entire defect produced by downward rotation of the medial lip. Millard's lateral advancement flap becomes unnecessary. A lateral approach to primary nasal reconstruction allows the lateral C flap to be used to construct the nasal floor and sill. The method is described using a physics-based surgical simulator. RESULTS:Long-term results of the method are demonstrated with four patients with 15 to 25-year follow-up. None of these patients had any revisions to the lip or nose. CONCLUSIONS:The Murawski repair was the first to modify the Millard II repair by sharpening the medial columellar incision, eliminating the need for a lateral advancement flap. This motif was put forth in the years to follow by Mohler and Cutting. Long-term results of the method are presented.

PURPOSE/OBJECTIVE:To elucidate long-term sequelae of radiation therapy (RT) in head and neck cancer (HNC) patients, a multi-center prospective study, Clinical Registry of Dental Outcomes in Head and Neck Cancer Patients (OraRad), was established with tooth failure as its primary outcome. We report tooth failure and associated risk factors. METHODS:Demographics, cancer and dental disease characteristics were documented in 572 HNC patients at baseline and 6, 12, 18, and 24 months after RT. Eligible patients were age 18 or older, diagnosed with HNC, and receiving RT to treat HNC. Tooth failure during follow-up was defined as losing a tooth or having a tooth deemed hopeless. Analyses of time to first tooth-failure event and number of teeth that failed used Kaplan-Meier estimators, Cox regression, and generalized linear models. RESULTS:At 2 years, the estimated fraction of tooth failure was 17.8% (95% confidence interval [CI]: 14.3%-21.3%). Number of teeth that failed was higher for those with fewer teeth at baseline (p<0.0001), greater reduction in salivary flow rate (p=0.013), and non-compliance with daily oral hygiene (p=0.03). Patients with dental caries at baseline had higher risk of tooth failure with decreased salivary flow. Patients who were oral hygiene non-compliant at baseline but compliant at all follow-up visits had the fewest teeth that failed; greatest tooth failure occurred in participants who were non-compliant at baseline and follow-up. CONCLUSION/CONCLUSIONS:Despite pre-RT dental management, substantial tooth failure occurs within 2 years after RT for HNC. Identified factors may help to predict or reduce risk of post-RT tooth failure.

Many Chinese Americans experience certain barriers (e.g., low income, English as a second language, lack of insurance, cultural differences, discrimination) when they seek oral healthcare services. These barriers may contribute to health disparities by discouraging use (leading to reduced utilization) of preventive and treatment services. This research adopts a modeling approach to develop theory that accounts for dynamic relationships operating at multiple levels, from individuals to families to communities. A multi-method and multi-level modeling approach allows for the interaction of factors at different levels of aggregation. This research applies spatially explicit agent-based modeling to examine how demographic, socioeconomic, and geographic factors shape access to oral healthcare for low-income Chinese Americans in New York City. The simulation model developed in this research was used to test different intervention scenarios involving community health workers who facilitate care coordination and other health promotion activities. In addition to demographic characteristics and socioeconomic factors, this study also considers geographic factors and spatial behavior, such as distance and activity space. The overarching contribution of this study is to provide a complex systems science framework to better understand access to oral healthcare for urban Chinese Americans, toward adapting it for other racial/ethnic minority groups, by integrating health-seeking behaviors at the individual level, barriers to care at multiple levels, and opportunities for health promotion at the community level.