Department of Otolaryngology—Head and Neck Surgery Works
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Item Specialized pro-resolving mediator lipidome and 16S rRNA bacterial microbiome data associated with human chronic rhinosinusitis(Elsevier, 2021-04-01) Vickery, Thad W.; Armstrong, Michael; Kofonow, Jennifer M.; Robertson, Charles E.; Kroehl, Miranda E.; Reisdorph, Nichole A.; Ramakrishnan, Vijay R.; Frank, Daniel N.; Otolaryngology -- Head and Neck Surgery, School of MedicineChronic rhinosinusitis (CRS) is a clinical syndrome defined by symptoms including nasal congestion, facial pain and pressure, anosmia, and rhinorrhea lasting more than 12 weeks. Several mechanistically distinct processes lead to the development of clinical symptoms in CRS including innate immune dysfunction, dysregulated eicosanoid metabolism and perturbations in host-microbiome interactions [1]. We developed a database comprised of patient demographic information, lipid mediator metabolomic profiles, and 16S bacterial rRNA gene sequence data from 66 patients undergoing endoscopic sinus surgery. Briefly, ethmoid sinus tissue and middle meatal swabs were collected from patients, including non-CRS controls, CRS with polyps (CRSwNP), and CRS without polyps (CRSsNP). Lipid mediator pathways from arachidonic acid (AA) and docosahexanoic acid (DHA) were analyzed by liquid chromatography/tandem mass spectrometry. Bacterial taxa were profiled in parallel by 16S rRNA gene sequencing. This database provides a useful compendium of AA/DHA metabolomic profiles and associated bacterial microbiota in patients with varying disease subtypes, demographics, and risk factors/comorbidities.Item Virtual Tumor Boards for Remote Learning in Head and Neck Surgical Oncology(American Medical Association, 2023) Papazian, Michael R.; Chow, Michael; Weed, Donald; Liu, Jeffrey C.; Bewley, Arnaud F.; Moore, Michael G.; Givi, Babak; Otolaryngology -- Head and Neck Surgery, School of MedicineImportance: In addition to their patient management value, multidisciplinary tumor boards have been recognized as effective learning tools. However, the value of using a virtual tumor board as a learning tool for head and neck surgical oncology fellows has not been studied. Objective: To describe the structure and content of the American Head and Neck Society (AHNS) Virtual Tumor Board and assess its educational value as perceived by attendees. Design, setting, and participants: All sessions of the AHNS Virtual Tumor Board from April 8, 2020, to June 1, 2022, were reviewed. Topics, presenters, participants, and viewership data were collected as of October 15, 2022, from session recordings posted to an online video sharing and social media platform. Additionally, an anonymous, 14-question online survey was designed to elicit feedback from head and neck surgery trainees on virtual tumor board engagement, strengths, and weaknesses. The survey was electronically distributed in June and July 2022 to the 101 fellows enrolled in AHNS-accredited programs between July 1, 2020, and June 30, 2022. Main outcomes and measures: The primary aim was to tabulate online viewership of the sessions. The secondary aim was to qualitatively assess the experience of head and neck trainees with the AHNS Virtual Tumor Board using a survey. Results: Forty-two sessions of the virtual tumor board were held between April 8, 2020, and June 1, 2022. Almost all sessions (41 [98%]) were case based. One hundred and sixteen cases were presented, representing 2 to 3 cases per session, by 75 unique faculty members. Each session was viewed a mean of 217 times (range, 64-2216 views). In the 2021 to 2022 academic year, a mean of 60 viewers (range, 30-92 viewers) attended each live session. In all, 29 survey responses were collected from 101 fellows in AHNS-accredited programs (29% response rate). Most respondents felt the format allowed for excellent teaching (18 of 26 respondents [69%]) and discussion (19 of 26 respondents [73%]). Most respondents (22 of 29 respondents [76%]) believed that practicing head and neck surgeons would benefit from the sessions. Conclusions and relevance: This survey study found that the AHNS Virtual Tumor Board was well-attended and well-reviewed by head and neck surgical oncology trainees. The virtual tumor board format could be used as model of remote learning for other organizations.Item Impact of Airline Secondhand Tobacco Smoke Exposure on Respiratory Health and Lung Function Decades After Exposure Cessation(Elsevier, 2022) Diaz del Valle, Fernando; Zakrajsek, Jonathan K.; Min, Sung-Joon; Koff, Patricia B.; Bell, Harold W.; Kincaid, Keegan A.; Frank, Daniel N.; Ramakrishnan, Vijay; Ghosh, Moumita; Vandivier, R. William; Otolaryngology -- Head and Neck Surgery, School of MedicineBackground: Twenty-five percent to 45% of COPD is caused by exposures other than active smoking. Secondhand tobacco smoke (SHS) has been suggested as an independent cause of COPD, based on its association with increased respiratory symptoms and a small decrease in lung function, but its impact on respiratory health and lung function after exposure cessation has not been explored. Research question: What are the consequences of airline SHS exposure on respiratory health and lung function decades after cessation? Study design and methods: We performed a cohort study involving flight attendants because of their exposure to SHS that stopped > 20 years ago. We included subjects ≥ 50 years of age with > 1 year vs ≤ 1 year of airline SHS exposure (ie, exposed vs unexposed). Respiratory quality of life, as determined by the St. George's Respiratory Questionnaire (SGRQ), was the primary outcome for respiratory health. Key secondary outcomes included general quality of life (the Rand Corporation modification of the 36-item Short Form Health Survey Questionnaire; RAND-36), respiratory symptoms (COPD Assessment Test; CAT), and spirometry. Results: The study enrolled 183 SHS-exposed and 59 unexposed subjects. Exposed subjects were 66.7 years of age, and 90.7% were female. They were hired at 23.8 years of age, were exposed to airline SHS for 16.1 years, and stopped exposure 27.5 years before enrollment. Prior SHS exposure was associated with worsened SGRQ (6.7 units; 95% CI, 2.7-10.7; P = .001), RAND-36 physical and social function, and CAT vs unexposed subjects. SHS exposure did not affect prebronchodilator spirometry or obstruction, but was associated with lower postbronchodilator FEV1 and FEV1/FVC, total lung capacity, and diffusing capacity of the lungs for carbon monoxide in a subset of subjects. Former smoking and SHS exposure synergistically worsened SGRQ (β = 8.4; 95% CI, 0.4-16.4; P = .04). SHS exposure in people who never smoked replicated primary results and was associated with worsened SGRQ vs unexposed people (4.7 units; 95% CI, 0.7-7.0; P = .006). Interpretation: Almost three decades after exposure ended, airline SHS exposure is strongly and dose-dependently associated with worsened respiratory health, but less robustly associated with airflow abnormalities used to diagnose COPD.Item Transcriptional profiling reveals potential involvement of microvillous TRPM5-expressing cells in viral infection of the olfactory epithelium(Springer Nature, 2021-03-30) Baxter, B. Dnate’; Larson, Eric D.; Merle, Laetitia; Feinstein, Paul; Gentile Polese, Arianna; Bubak, Andrew N.; Niemeyer, Christy S.; Hassell, James, Jr.; Shepherd, Doug; Ramakrishnan, Vijay R.; Nagel, Maria A.; Restrepo, Diego; Otolaryngology -- Head and Neck Surgery, School of MedicineBackground: Understanding viral infection of the olfactory epithelium is essential because the olfactory nerve is an important route of entry for viruses to the central nervous system. Specialized chemosensory epithelial cells that express the transient receptor potential cation channel subfamily M member 5 (TRPM5) are found throughout the airways and intestinal epithelium and are involved in responses to viral infection. Results: Herein we performed deep transcriptional profiling of olfactory epithelial cells sorted by flow cytometry based on the expression of mCherry as a marker for olfactory sensory neurons and for eGFP in OMP-H2B::mCherry/TRPM5-eGFP transgenic mice (Mus musculus). We find profuse expression of transcripts involved in inflammation, immunity and viral infection in TRPM5-expressing microvillous cells compared to olfactory sensory neurons. Conclusion: Our study provides new insights into a potential role for TRPM5-expressing microvillous cells in viral infection of the olfactory epithelium. We find that, as found for solitary chemosensory cells (SCCs) and brush cells in the airway epithelium, and for tuft cells in the intestine, the transcriptome of TRPM5-expressing microvillous cells indicates that they are likely involved in the inflammatory response elicited by viral infection of the olfactory epithelium.Item Clinical Validation and Extension of an Automated, Deep Learning–Based Algorithm for Quantitative Sinus CT Analysis(American Society of Neuroradiology, 2022) Massey, C. J.; Ramos, L.; Beswick, D. M.; Ramakrishnan, V. R.; Humphries, S. M.; Otolaryngology -- Head and Neck Surgery, School of MedicineBackground and purpose: Sinus CT is critically important for the diagnosis of chronic rhinosinusitis. While CT is sensitive for detecting mucosal disease, automated methods for objective quantification of sinus opacification are lacking. We describe new measurements and further clinical validation of automated CT analysis using a convolutional neural network in a chronic rhinosinusitis population. This technology produces volumetric segmentations that permit calculation of percentage sinus opacification, mean Hounsfield units of opacities, and percentage of osteitis. Materials and methods: Demographic and clinical data were collected retrospectively from adult patients with chronic rhinosinusitis, including serum eosinophil count, Lund-Kennedy endoscopic scores, and the SinoNasal Outcomes Test-22. CT scans were scored using the Lund-Mackay score and the Global Osteitis Scoring Scale. CT images were automatically segmented and analyzed for percentage opacification, mean Hounsfield unit of opacities, and percentage osteitis. These readouts were correlated with visual scoring systems and with disease parameters using the Spearman ρ. Results: Eighty-eight subjects were included. The algorithm successfully segmented 100% of scans and calculated features in a diverse population with CT images obtained on different scanners. A strong correlation existed between percentage opacification and the Lund-Mackay score (ρ = 0.85, P < .001). Both percentage opacification and the Lund-Mackay score exhibited moderate correlations with the Lund-Kennedy score (ρ = 0.58, P < .001, and ρ = 0.58, P < .001, respectively). The percentage osteitis correlated moderately with the Global Osteitis Scoring Scale (ρ = 0.48, P < .001). Conclusions: Our quantitative processing of sinus CT images provides objective measures that correspond well to established visual scoring methods. While automation is a clear benefit here, validation may be needed in a prospective, multi-institutional setting.Item Olfactory Function After Surgical Treatment of CRS: A Comparison of CRS Patients to Healthy Controls(Sage, 2021) Mattos, Jose L.; Soler, Zachary M.; Schlosser, Rodney J.; Mace, Jess C.; Alt, Jeremiah A.; Ramakrishnan, Vijay R.; Payne, Spencer C.; Smith, Timothy L.; Beswick, Daniel M.; Otolaryngology -- Head and Neck Surgery, School of MedicineBackground: Many patients with chronic rhinosinusitis (CRS) have persistent olfactory dysfunction (OD) following endoscopic sinus surgery (ESS). Few studies compare outcomes to control subjects so it is unknown if residual OD is due to persistent CRS. Objective: Compare postoperative measures of OD in case patients with CRS to healthy controls without sinonasal disease. Methods: Prospective, observational, multicenter cohort study between October, 2016 and May, 2019. Case participants were selected from referred adult patients diagnosed with CRS, with or without nasal polyposis (NP), electing ESS as subsequent treatment modality. Controls voluntarily enrolled from a community-based sample without a history of CRS. Primary outcomes included measures of preoperative and postoperative OD using "Sniffin' Stick" pens which summarize odorant threshold (T), discrimination (D), and identification (I) scores. Secondary outcomes included the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) survey and olfactory cleft endoscopy scores (OCES). Results: Outcomes were compared between 113 cases and 164 controls of similar average age and gender. Cases reported significantly worse baseline Sniffin' Sticks TDI total scores (-6.8[SE ± 1.0]; 95% CI: -4.9 to -8.7), QOD-NS (8.9[SE ± 1.1]; 95% CI: 6.8-10.9), and OCES (3.5[SE ± 0.4]; 95% CI: 2.9-4.2) on average. Cases reported significant postoperative improvement in TDI total score (3.7[SD ± 8.2]; 95% CI: 2.2-5.2), QOD-NS (-5.9[SD ± 8.7]; 95% CI: -7.6 to -4.3), and OCES (-1.7[SD ± 3.8]; 95% CI: -2.7 to -0.8) on average, while 63% of anosmics reported improved postoperative olfaction. Multivariate regression identified that NP (OR = 0.4; 95% CI: 0.2-1.0) and previous ESS (OR = 0.3; 95% CI: 0.1-0.8) decreased the odds of postoperative improvement equal to mean TDI scores of controls, while septoplasty increased those odds (OR = 4.5; 95% CI: 1.5-13.7). Conclusion: ESS improved olfactory metrics and restored olfactory function in approximately 50% of patients with CRS to that of healthy controls. Concurrent septoplasty increased the likelihood of achieving normal olfaction, while NP and previous ESS decreased those odds.Item Temperament in Toddlers With and Without Prelingual Hearing Loss(American Speech-Language-Hearing Association, 2024) Castellanos, Irina; Houston, Derek M.; Otolaryngology -- Head and Neck Surgery, School of MedicinePurpose: The purpose of this study is to examine parent-reported ratings of temperament in toddlers with and without prelingual hearing loss. Method: The parent-completed Early Childhood Behavior Questionnaire (ECBQ) was used to assess temperament in toddlers aged 18-36 months. Three dimensions of temperament were examined: surgency, negative affectivity, and effortful control. Analyses were conducted to (a) examine differences in temperament across toddlers with and without prelingual hearing loss; (b) examine possible associations between temperament, demographic, and communication factors; and (c) determine if the ECBQ is sensitive to differences in hearing, communication, and listening skills among toddlers with prelingual hearing loss. Results: The parent-completed ECBQ revealed that toddlers with prelingual hearing loss differed from their hearing peers on some but not all dimensions of temperament. Specifically, children with prelingual hearing loss were rated as displaying higher levels of surgency and lower levels of effortful control but comparable levels of negative affectivity when compared to their hearing peers. Regression analyses revealed that chronological age and communication strategy predicted scores of effortful control in toddlers with prelingual hearing loss, whereas chronological age alone predicted scores of effortful control in toddlers with hearing. Finally, the ECBQ appears to contain "listening" items that skew (lower) levels of effortful control in toddlers with prelingual hearing loss, such that only the group effect of higher levels of surgency remained after removing these "listening" items. Correlations between the original and our modified ECBQ (removing the "listening" items) revealed strong associations, reflective of high construct validity. Conclusions: This was the first study to measure temperament in toddlers with prelingual hearing loss using the ECBQ. Our results revealed differences between children with and without prelingual hearing loss centering on the dimension of surgency. Examining differences in temperament during the toddler period of development may be particularly important and useful for predicting functional outcomes following prelingual hearing loss.Item Histopathologic Features of Mucosal Head and Neck Cancer Cachexia(Hindawi, 2024-06-27) Jones, Alexander J.; Novinger, Leah J.; Bonetto, Andrea; Davis, Kyle P.; Giuliano, Marelle M.; Mantravadi, Avinash V.; Sim, Michael W.; Moore, Michael G.; Yesensky, Jessica A.; Otolaryngology -- Head and Neck Surgery, School of MedicineObjective: Determine the histopathologic features that correlate with head and neck cancer (HNC) cachexia. Methods: A single-institution, retrospective study was performed on adults with HPV-negative, mucosal squamous cell carcinoma of the aerodigestive tract undergoing resection and free flap reconstruction from 2014 to 2019. Patients with distant metastases were excluded. Demographics, comorbidities, preoperative nutrition, and surgical pathology reports were collected. Comparisons of histopathologic features and cachexia severity were made. Results: The study included 222 predominantly male (64.9%) patients aged 61.3 ± 11.8 years. Cachexia was identified in 57.2% patients, and 18.5% were severe (≥15% weight loss). No differences in demographics were identified between the groups. Compared to control, patients with severe cachexia had lower serum hemoglobin (p=0.048) and albumin (p < 0.001), larger tumor diameter (p < 0.001), greater depth of invasion (p < 0.001), and elevated proportions of pT4 disease (p < 0.001), pN2-N3 disease (p=0.001), lymphovascular invasion (p=0.009), and extranodal extension (p=0.014). Multivariate logistic regression identified tumor size (OR [95% CI] = 1.36 [1.08-1.73]), oral cavity tumor (OR [95% CI] = 0.30 [0.11-0.84]), and nodal burden (OR [95% CI] = 1.16 [0.98-1.38]) as significant histopathologic contributors of cancer cachexia. Conclusions: Larger, more invasive tumors with nodal metastases and aggressive histologic features are associated with greater cachexia severity in mucosal HNC.Item Generating high-fidelity cochlear organoids from human pluripotent stem cells(Elsevier, 2023) Moore, Stephen T.; Nakamura, Takashi; Nie, Jing; Solivais, Alexander J.; Aristizábal-Ramírez, Isabel; Ueda, Yoshitomo; Manikandan, Mayakannan; Reddy, V. Shweta; Romano, Daniel R.; Hoffman, John R.; Perrin, Benjamin J.; Nelson, Rick F.; Frolenkov, Gregory I.; Chuva de Sousa Lopes, Susana M.; Hashino, Eri; Otolaryngology -- Head and Neck Surgery, School of MedicineMechanosensitive hair cells in the cochlea are responsible for hearing but are vulnerable to damage by genetic mutations and environmental insults. The paucity of human cochlear tissues makes it difficult to study cochlear hair cells. Organoids offer a compelling platform to study scarce tissues in vitro; however, derivation of cochlear cell types has proven non-trivial. Here, using 3D cultures of human pluripotent stem cells, we sought to replicate key differentiation cues of cochlear specification. We found that timed modulations of Sonic Hedgehog and WNT signaling promote ventral gene expression in otic progenitors. Ventralized otic progenitors subsequently give rise to elaborately patterned epithelia containing hair cells with morphology, marker expression, and functional properties consistent with both outer and inner hair cells in the cochlea. These results suggest that early morphogenic cues are sufficient to drive cochlear induction and establish an unprecedented system to model the human auditory organ.Item Inflammation resolution and specialized pro-resolving lipid mediators in chronic rhinosinusitis(Taylor & Francis, 2023) Robinson, Peyton Z.; Frank, Daniel N.; Ramakrishnan, Vijay R.; Otolaryngology -- Head and Neck Surgery, School of MedicineIntroduction: In chronic rhinosinusitis (CRS), a complex pathophysiology results from varied pro-inflammatory stimuli but is consistently characterized by classic cellular, molecular, and microbial alterations. Normally, endogenous specialized pro-resolving mediators (SPM) actively promote resolution of inflammation through numerous pathways, including those involved in host antimicrobial defense. However, these pathways appear to be disrupted in CRS. Areas covered: This paper describes features of CRS in the context of chronic tissue inflammation, and potential mechanisms by which specialized pro-resolving mediators promote active resolution of tissue inflammation. Expert opinion: Temporal phases of resolution must be tightly regulated to successfully resolve inflammation in CRS while preserving tissue functions such as barrier maintenance and special sensory function. Dysregulation of SPM enzymatic pathways has been recently shown in CRS and is associated with disease phenotypes and microbial colonization patterns. Current research in animal models and in vitro human cell culture, as well as human dietary studies, demonstrate relevant changes in cell signaling with lipid mediator bioavailability. Further clinical research may provide insight into the therapeutic value of this approach in CRS.