Faculty Bibliography

UNLABELLED:Facial transplantation (FT) has advanced extensively over the past two decades, with over 40 transplants performed to date. Over this time, the FT literature has evolved as well, from early discussions on ethics and feasibility of FT to functional outcomes reports more recently. We aimed to evaluate the entire body of FT literature to identify trends in publications over time in addition to current existing gaps in the field. METHODS/UNASSIGNED:We conducted a comprehensive bibliometric analysis of the published FT literature from 1994, the first year FT was mentioned in the literature, through July 2020. Co-authorship and keyword information were analyzed using VOSviewer. Articles were manually categorized based on keywords and their aim to provide insight on trends. RESULTS/UNASSIGNED:A total of 2182 articles were identified. Analysis identified the top 50 publishing authors in the field and demonstrated co-authorship linkage between 84.8% of the top 1000 authors. Clinical surgical techniques, protocols, and experiments were the most frequently published category. Within clinical outcomes, immunologic outcomes were most frequent, while psychosocial were the lowest. Gaps were identified in long-term outcomes reporting and patient-reported outcomes, with physician-reported outcomes heavily outweighing patient-reported outcomes. CONCLUSIONS/UNASSIGNED:As the field continues to evolve, rigorous tracking of publication patterns over time will encourage development of a more robust evidence base, identify gaps in the published literature, and highlight opportunities to enhance collaboration in the field. This data will provide surgeons and research institutions with information to further improve this life-changing procedure.

Background/UNASSIGNED:Despite significant advances in the management of frontal sinus fractures, there is still a paucity of large-cohort data, and a comprehensive synthesis of the current literature is warranted. The purpose of this study was to present an evidence-based overview of frontal sinus fracture management and outcomes. Methods/UNASSIGNED:A comprehensive literature search of PubMed and MEDLINE was conducted for studies published between 1992 and 2020 investigating frontal sinus fractures. Data on fracture type, intervention, and outcome measurements were reported. Results/UNASSIGNED:In total, 456 articles were identified, of which 53 met our criteria and were included in our analysis. No statistically significant difference in mechanism of injury, fracture pattern, form of management, or total complication rate was identified. We found a statistically significant increase in complication rates in patients with nasofrontal outflow tract injury compared with those without. Conclusions/UNASSIGNED:Frontal sinus fracture management is a challenging clinical situation, with no widely accepted algorithm to guide appropriate management. Thorough clinical assessment of the fracture pattern and associated injuries can facilitate clinical decision-making.

OBJECTIVE:The effectiveness of µ-opioid receptor (MOPr) agonists for treatment of visceral pain is compromised by constipation, respiratory depression, sedation and addiction. We investigated whether a fentanyl analogue, (±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP), which preferentially activates MOPr in acidified diseased tissues, would inhibit pain in a preclinical model of inflammatory bowel disease (IBD) without side effects in healthy tissues. DESIGN/METHODS:Antinociceptive actions of NFEPP and fentanyl were compared in control mice and mice with dextran sodium sulfate colitis by measuring visceromotor responses to colorectal distension. Patch clamp and extracellular recordings were used to assess nociceptor activation. Defecation, respiration and locomotion were assessed. Colonic migrating motor complexes were assessed by spatiotemporal mapping of isolated tissue. NFEPP-induced MOPr signalling and trafficking were studied in human embryonic kidney 293 cells. RESULTS:NFEPP inhibited visceromotor responses to colorectal distension in mice with colitis but not in control mice, consistent with acidification of the inflamed colon. Fentanyl inhibited responses in both groups. NFEPP inhibited the excitability of dorsal root ganglion neurons and suppressed mechanical sensitivity of colonic afferent fibres in acidified but not physiological conditions. Whereas fentanyl decreased defecation and caused respiratory depression and hyperactivity in mice with colitis, NFEPP was devoid of these effects. NFEPP did not affect colonic migrating motor complexes at physiological pH. NFEPP preferentially activated MOPr in acidified extracellular conditions to inhibit cAMP formation, recruit β-arrestins and evoke MOPr endocytosis. CONCLUSION/CONCLUSIONS:In a preclinical IBD model, NFEPP preferentially activates MOPr in acidified microenvironments of inflamed tissues to induce antinociception without causing respiratory depression, constipation and hyperactivity.

Pediatric voice disorders are increasing being noted as a barrier to success in school and socialization. Significant advances over the past decade in evaluation, diagnosis, and management of pediatric voice disorders have improved both short-term and long-term outcomes. Practitioners should have a thorough understanding of anatomy and physiology, accurately work up a pediatric voice disorder, and efficiently treat voice disorders. Comprehensive voice evaluation in children is essential to properly assessing pediatric dysphonia. Diagnosis and treatment are best managed by a multidisciplinary team. Accurate diagnosis allows for effective treatment, which includes voice therapy, medical therapy, and surgical intervention as needed.

Skeletal conditions represent a considerable challenge to health systems globally. Barriers to effective therapeutic development include a lack of accurate preclinical tissue and disease models. Most recently, work was attempted to present a novel whole organ approach to modeling human bone and cartilage tissues. These self-assembling skeletal organoids mimic the cellular milieu and extracellular organization present in native tissues. Bone organoids demonstrated osteogenesis and micro vessel formation, and cartilage organoids showed evidence of cartilage development and maturation. Skeletal organoids derived from both bone and cartilage tissues yielded spontaneous polarization of their cartilaginous and bone components. Using these hybrid skeletal organoids, we successfully generated "mini joint" cultures, which we used to model inflammatory disease and test Adenosine (A_2A ) receptor agonists as a therapeutic agent. The work and respective results indicated that skeletal organoids can be an effective biological model for tissue development and disease as well as to test therapeutic agents.

BACKGROUND:The Affordable Care Act sought to improve access to health care for low-income individuals. This study aimed to assess whether expansion of Medicaid coverage increased rates of post-mastectomy reconstruction (PMR) for patients who had Medicaid or no insurance. METHODS:A retrospective analysis performed through the National Cancer Database examined women who underwent PMR and were uninsured or had Medicaid, private insurance, or Medicare, and whose race/ethnicity, age, and state expansion status were known. Trends in the use of PMR after passage of Medicaid expansion in 2014 were evaluated. RESULTS:In all states and at all time periods, patients with private insurance were about twice as likely to undergo PMR as patients who had Medicaid or no insurance. In 2016, only 28.7 % of patients with Medicaid or no insurance in nonexpansion states underwent PMR (p < 0.001) compared with 38.5 % of patients in expansion states (p < 0.001). Patients in expansion states also have higher levels of education, higher income, and greater likelihood of living in metropolitan areas. Additionally, patients in all states saw an increase in early-stage disease, with a concomitant reduction in late disease, but this change was greater in expansion states than in non-expansion states. CONCLUSIONS:Expansion states have larger proportions of patients undergoing PMR than non-expansion states. This difference stems from significant differences in income, education, comorbidities, race, and location. Large metropolitan areas have the largest number of patients undergoing PMR, whereas rural areas have the least.

Oral cancer patients report sensitivity to spicy foods and liquids. The mechanism responsible for chemosensitivity induced by oral cancer is not known. We simulate oral cancer-induced chemosensitivity in a xenograft oral cancer mouse model using two-bottle choice drinking and conditioned place aversion assays. An anatomic basis of chemosensitivity is shown in increased expression of TRPV1 in anatomically relevant trigeminal ganglion (TG) neurons in both the xenograft and a carcinogen (4-nitroquinoline 1-oxide)-induced oral cancer mouse models. The percent of retrograde labeled TG neurons that respond to TRPV1 agonist, capsaicin, is increased along with the magnitude of response as measured by calcium influx, in neurons from the cancer models. To address the possible mechanism of TRPV1 sensitivity in tongue afferents, we study the role of PAR₂, which can sensitize the TRPV1 channel. We show co-expression of TRPV1 and PAR₂ on tongue afferents and using a conditioned place aversion assay, demonstrate that PAR₂ mediates oral cancer-induced, TRPV1-evoked sensitivity in an oral cancer mouse model. The findings provide insight into oral cancer-mediated chemosensitivity.