Department of Otolaryngology, Head and Neck Surgery

PURPOSE OF REVIEW: Patients with cleft lip -palate (CLP) experience morbidity and social stigma, particularly in low-income and middle-income countries (LMICs) such as those of sub-Saharan Africa (SSA). Delays in treatment secondary either to lack of awareness, skills, equipment and consumables; poor health infrastructure, limited resources or a combination of them, has led to SSA having the highest rates of death and second highest rates of disability-adjusted life years in patients with CLP globally. Here we review current perspectives on the state of comprehensive cleft lip and palate repair in Africa. RECENT FINDINGS: To bridge gaps in government health services, nongovernmental organizations (NGOs) have emerged to provide care through short-term surgical interventions (STSIs). These groups can effect change through direct provision of care, whereas others strengthen internal system. However, sustainability is lacking as there continue to be barriers to achieving comprehensive and longitudinal cleft care in SSA, including a lack of awareness of CLP as a treatable condition, prohibitive costs, poor follow-up, and insufficient surgical infrastructure. With dedicated local champions, a comprehensive approach, and reliable partners, establishing sustainable CLP services is possible in countries with limited resources. SUMMARY: The replacement of CLP missions with locally initiated, internationally supported capacity building initiatives, integrated into local healthcare systems will prove sustainable in the long-term.

Text-to-image artificial intelligence (AI) programs are popular public-facing tools that generate novel images based on user prompts. Given that they are trained from Internet data, they may reflect societal biases, as has been shown for text-to-text large language model programs. We sought to investigate whether 3 common text-to-image AI systems recapitulated stereotypes held about surgeons and other health care professionals. All platforms queried were able to reproduce common aspects of the profession including attire, equipment, and background settings, but there were differences between programs most notably regarding visible race and gender diversity. Thus, historical stereotypes of surgeons may be reinforced by the publics use of text-to-image AI systems, particularly those without procedures to regulate generated output. As AI systems become more ubiquitous, understanding the implications of their use in health care and for health care-adjacent purposes is critical to advocate for and preserve the core values and goals of our profession.

OBJECTIVE: This scoping review aims to contribute a descriptive analysis of the craniomaxillofacial trauma (CMF trauma) literature in low- and middle-income countries (LMICs) to identify knowledge gaps, direct future research, and inform policy. DATA SOURCES: PubMed/MEDLINE, Cochrane Review, EMBASE, ClinicalTrials.gov, and Google Scholar from January 1, 2012 to December 10, 2023. REVIEW METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guided reporting, and the PRISMA flowchart documented database searches. Specific, predefined search terms and inclusion criteria were used for screening, and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist was used for quality assessment. The search yielded 54 articles, with 13 meeting the inclusion criteria. Key findings were summarized and divided into 7 categories. RESULTS: There were 10,420 patients (7739 [74.3%] male, 2681 [25.7%] female) with a male-to-female ratio of 2.9:1. The mean peak age of incidence of CMF trauma was 30.8 years, ranging from 20 to 40 years. Road traffic accidents were the leading cause (60.4%), followed by assault (27.2%) and falls (12.2%). The most common injuries were soft tissue injury (31.7%), isolated mandibular fracture (22.8%), and isolated middle-third of mandible fracture (18.1%). The most common treatments were closed reduction and immobilization (29.5%), conservative management (27.6%), and open reduction and internal fixation (19.6%). Most patients (77.8%) experienced a treatment delay due to a lack of fixation materials (54.8%) or surgeon unavailability (35.7%). CONCLUSION: CMF trauma remains a significant cause of global morbidity, yet there remains a lack of high-quality, CMF trauma-specific data in LMICs. Country-specific investigations are required to enhance knowledge and inform novel interventions. Implementing policy change must be community-specific and account for unique cultural barriers, attitudes, and behaviors to maximize patient care outcomes.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a debilitating disease with poor survival rates. While the epidermal growth factor receptor (EGFR)-targeting antibody Cetuximab is approved for treatment, responses are limited and the molecular mechanisms driving resistance remain incompletely understood. METHODS: To better understand how cells survive without EGFR activity, we developed an EGFR knockout derivative of the UM-SCC-92 cell line using CRISPR/Cas9 technology. We then characterized changes to the transcriptome with RNAseq and changes in response to kinase inhibitors with resazurin cell viability assays. Finally, we tested if inhibitors with activity in the EGFR knockout model also had synergistic activity in combination with EGFR inhibitors in either wild type UM-SCC-92 cells or a known Cetuximab-resistant model. RESULTS: Functional and molecular analysis showed that knockout cells had decreased cell proliferation, upregulation of FGFR1 expression, and an enhanced mesenchymal phenotype. In fact, expression of common EMT genes including VIM, SNAIL1, ZEB1 and TWIST1 were all upregulated in the EGFR knockout. Surprisingly, EGFR knockout cells were resistant to FGFR inhibitor monotherapies, but sensitive to combinations of FGFR and either XIAP or IGF-1R inhibitors. Accordingly, both wild type UM-SCC-92 and Cetuximab-resistant UM-SCC-104 cells with were sensitive to combined inhibition of EGFR, FGFR and either XIAP or IGF-1R. CONCLUSIONS: These data offer insights into EGFR inhibitor resistance and show that resistance to EGFR knockout likely occurs through a complex network of kinases. Future studies of cetuximab-resistant HNSCC tumors are warranted to determine if this EMT phenotype and/or multi-kinase resistance is observed in patients.

Long-term management of inflammatory skin diseases is challenging because of side effects from repeated use of systemic treatments or topical corticosteroids. This study sought to identify the mechanisms and developmental therapeutics for these diseases using genetic models and pharmacological approaches. We found that mice overexpressing SMAD7 in keratinocytes but not mice overexpressing the N-terminal domain of SMAD7 (i.e., N-SMAD7) were resistant to imiquimod-induced T helper 1/17- and T helper 2-type inflammation. We generated a Tat-PYC-SMAD7 (truncated SMAD7 protein encompassing C-terminal SMAD7 and PY motif fused with cell-penetrating Tat peptide). Topically applied Tat-PYC-SMAD7 to inflamed skin entered cells upon contact and attenuated imiquimod-, 2,4-dinitrofluorobenzene-, and tape-stripping-induced inflammation. RNA-sequencing analyses of mouse skin exposed to these insults showed that in addition to inhibiting TGFβ/NF-κB, SMAD7 blunted IL-22/signal transducer and activator of transcription 3 activation and associated pathogenesis, which is due to SMAD7 transcriptionally upregulating IL-22 antagonist IL-22RA2. Mechanistically, SMAD7 facilitated nuclear translocation and DNA binding of C/EBPβ to IL22RA2 promoter for IL22RA2 transactivation. Consistent with the observations in mice mentioned earlier, transcript levels of IL22RA2 were increased in human atopic dermatitis and psoriasis lesions with clinical remission. Our study identified the anti-inflammation functional domain of SMAD7 and suggests the mechanism and feasibility for developing SMAD7-based biologics as a topical therapy for skin inflammatory disorders.

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OBJECTIVE: Identification of anatomical landmarks is essential for interpretation of video fluoroscopic swallow studies (VFSS). This investigation sought to confirm the location of essential laryngeal landmarks and determine clinician accuracy in structure identification on VFSS. METHODS: A single human cadaver was used to generate unmarked standard lateral and anterior-posterior (AP) fluoroscopic images. Essential laryngeal structures (e.g., true vocal fold, arytenoid) were directly identified using a guidewire placed through an endoscope while obtaining corresponding marked fluoroscopic images. Licensed clinicians (speech-language pathologists [SLP], laryngologists) and trainees (otolaryngology residents, SLP clinical fellows [CF]) identified 18 structures (9 lateral, 9 AP) on unmarked images. Answers were compared to corresponding marked images. The percentage of accurate identification was calculated for each clinician and then compared between groups using t-tests. RESULTS: Twenty-four individuals (10 SLPs, 1 CF, 9 residents, 4 laryngologists) from six institutions completed structure identification. Mean overall accuracy was 41.7 ± 13.0% (range 18.8-68.8%). There were no significant differences in mean overall accuracy between trainees (41.9 ± 12.9%) and clinicians (42.0 ± 13.1%), p = .97, or between SLPs (45.5 ± 12.8%) and physicians (38.9 ± 12.3%), p = .22. On average, participants were significantly more accurate identifying structures on lateral view (53.1 ± 16.1%) than AP (27.3 ± 22.8%), p < .001. Less than half of participants accurately identified the laryngeal ventricle, cricoid, epiglottic petiole, and the anterior commissure on lateral view. CONCLUSIONS: The ability of certified clinicians and trainees to correctly identify essential anatomic landmarks on swallowing fluoroscopy may be poor. Future work is needed to identify how we can train clinicians on more accurate identification of essential anatomic structures on swallowing fluoroscopy.Level of Evidence: NA.

Skull base surgery has evolved significantly since Harvey Cushings first descriptions in the early 1900s. Computer aided surgery (CAS) applications continue to expand; they include virtual surgical planning, augmented and virtual reality, 3D printing of models/cutting guides/implants, surgical navigation, and intraoperative imaging. The authors will review the current skull base CAS literature and propose a computer aided surgical workflow categorizing these applications into 3 phases: 1) Virtual planning, 2) Surgical execution, 3) Intraoperative verification.

OBJECTIVE/HYPOTHESIS: Oral cancers in the US-affiliated Pacific Islands are poorly described despite disproportionately higher incidences in certain jurisdictions. This study attempts to better characterize the incidence, staging, and management of oral cancers in this region. STUDY DESIGN: Retrospective Epidemiological Study. METHODS: A retrospective review was conducted across the US-affiliated Pacific Islands between 2007 and 2019. Patient data were obtained for individuals with primary head and neck cancers from the Pacific Regional Central Cancer Registry database. All cohorts were age-adjusted to the 2000 US Standard Population. Further analysis was performed on oral cavity cancers due to their clear predominance within the sample. RESULTS: A total of 585 patients with primary head and neck cancers were included. The average age was 54.5 ± 12.9 years, and most patients were male (76.8%). Oral cancer subsite analysis revealed the proportional incidence of buccal mucosa was higher in 5 of 9 jurisdictions when compared with the United States (p < 0.001). Tongue and lip cancers were not found to have significantly higher incidence proportions. Patients in the Pacific Islander group were less likely to be detected at earlier stages for cancers of the cheek and other mouth (p < 0.001), tongue (p < 0.001), and lips (p < 0.001) compared with the United States. CONCLUSIONS: Many Pacific Island populations are burdened with higher incidences of oral cancer with later staging. Further investigation is recommended to evaluate oral cancer-related outcomes and mortality in this region. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1899-1905, 2023.