Department of Otolaryngology—Head and Neck Surgery Works

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    Telemedicine in Otolaryngology During COVID-19: An Exploratory Assessment of Provider and Patient Attitudes
    (Sage, 2023) Alwani, Mohamedkazim; Campiti, Vincent; Nesemeier, Ryan; Vernon, Dominic; Shipchandler, Taha; Ting, Jonathan; Parker, Noah; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Objective: To determine provider and patient attitudes toward telemedicine in Otolaryngology-Head and Neck Surgery (OHNS). Methods: Otolaryngology practitioners conducting outpatient clinics at an academic tertiary referral center were provided with a pre-Study Provider Perception Questionnaire (pre-PPQ) designed to evaluate pre-study perception of telemedicine in otolaryngology. A post-study Provider Perception Questionnaire (post-PPQ) designed to evaluate elements similar to those constituting the PrePPQ was completed at 6 weeks. Additionally, following each visit, providers and patients completed Individual Encounter Survey Questionnaires (IESQ) to evaluate the virtual clinical encounter experience. Results: The pre-PPQ was completed by 29 providers, while the post-PPQ was completed by 12 providers. A total of 236 post-visit provider IESQs were completed, of which 208 were deemed successful. Audio/visual (AV) difficulties and limited server connectivity for the patient were most common causes for unsuccessful encounters. Providers reported that the most appropriate use of telemedicine, on both pre-PPQ and post-PPQ, was triaging patients to determine the need for in-person visits. The inability to perform a physical exam was rated as the primary barrier to telemedicine in OHNS on both pre-PPQ and post-PPQ. Patients strongly agreed with the statements, "My healthcare provider was able to understand my healthcare condition" and, "I felt comfortable communicating with my healthcare provider" 92.0% and 95.4% of the time, respectively. Conclusion: Both providers and patients demonstrated an overall positive attitude toward the use of telemedicine in the provision of otolaryngologic care.
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    CHD7 regulates otic lineage specification and hair cell differentiation in human inner ear organoid
    (Springer Nature, 2022-11-17) Nie, Jing; Ueda, Yoshitomo; Solivais, Alexander J.; Hashino, Eri; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Mutations in CHD7 cause CHARGE syndrome, affecting multiple organs including the inner ear in humans. We investigate how CHD7 mutations affect inner ear development using human pluripotent stem cell-derived organoids as a model system. We find that loss of CHD7 or its chromatin remodeling activity leads to complete absence of hair cells and supporting cells, which can be explained by dysregulation of key otic development-associated genes in mutant otic progenitors. Further analysis of the mutant otic progenitors suggests that CHD7 can regulate otic genes through a chromatin remodeling-independent mechanism. Results from transcriptome profiling of hair cells reveal disruption of deafness gene expression as a potential underlying mechanism of CHARGE-associated sensorineural hearing loss. Notably, co-differentiating CHD7 knockout and wild-type cells in chimeric organoids partially rescues mutant phenotypes by restoring otherwise severely dysregulated otic genes. Taken together, our results suggest that CHD7 plays a critical role in regulating human otic lineage specification and hair cell differentiation.
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    Simulation of laryngotracheal reconstruction with 3D-printed models and porcine cadaveric models
    (Wiley, 2022-08-09) Falls, Megan; Vincze, Jonathan; Brown, Joshua; Witsberger, Chelsey; Discolo, Christopher; Partain, Matthew; Rosen, Philip; Ting, Jonathan; Zopf, David; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Objectives: Laryngotracheal reconstruction (LTR) is a complex operation used to treat subglottic stenosis. The use of simulator models is a valuable tool in surgical trainee education, particularly for operations such as LTR that are less common outside high-volume centers. Three-dimensional (3D) printing of the human airway may provide an effective and more accessible alternative to porcine cadaveric models. The objective of this study is to compare the educational value of a 3D-printed model and a porcine cadaveric model as LTR simulation methods. Methods: Simulated LTR procedures were completed by 12 otolaryngology residents and a faculty physician on the cadaveric model and the 3D-printed simulator model. Both models were evaluated by fellowship-trained pediatric otolaryngologists to establish construct validity. Pre-procedure surveys of participants evaluated confidence and attitude toward models and post-procedure surveys evaluated confidence, overall impressions, relevance, content validity, and face validity. Results: Participants reported a similar mean increase in confidence after performing LTR on the 3D-printed model (14%) and cadaveric model (11%). Participants rated both models similarly for utility as an overall training tool and in teaching surgical planning and improving operative techniques. However, participants found the 3D-printed model more useful for teaching anatomy (p = .047). Conclusion: 3D-printed models have practical benefits over cadaveric models; they do not decompose and can be custom made to model a disease state such as subglottic stenosis. Participants reported a similar mean increase in confidence after using either simulation. The 3D-printed model is a promising simulation candidate as it compares well to an animal model and has the advantage of being more anatomically true to pediatric patients.
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    Developmental Outcomes in Early-Identified Children who are Hard of Hearing at 2 to 3 Years of Age
    (Wolters Kluwer, 2021) Stika, Carren J.; Eisenberg, Laurie S.; Carter, Alice S.; Johnson, Karen C.; Hammes Ganguly, Dianne M.; Henning, Shirley C.; DesJardin, Jean L.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Objectives: This study examined the psychosocial, adaptive behavior, and language outcomes of young children who are hard of hearing (HH) without additional disabilities or neurocognitive impairments. Relations between early developmental outcomes and child and parent demographic variables, and parenting stress and self-efficacy were also explored. Design: Participants were 39 children with early identified, permanent mild to severe hearing loss, between the ages of 2 and 3 years, and a comparison group of 47 children with normal hearing (NH). Developmental outcomes were measured using clinician-administered standardized tests and parent-completed behavior rating instruments specific to language, psychosocial functioning, and adaptive behavior. Mothers completed self-report measures that assess parenting stress and maternal self-efficacy. Results: The children who are HH were similar to the children with NH in terms of their psychosocial functioning and adaptive behavior, with the exception of their socialization skills. As a group, the children who are HH performed significantly worse than their peers with NH on all measures of language ability. Among the children who are HH, maternal self-efficacy showed a strong positive correlation with adaptive behavior outcomes; however, it failed to contribute unique variance above that explained by language ability and gender. Maternal self-efficacy was also significantly correlated with better psychosocial outcomes, but only parenting stress proved to be a significant predictor of child behavioral problems once other variables considered were in the model. Conclusions: Early-identified young children who are HH can demonstrate age-appropriate development in multiple domains, including language, psychosocial, and adaptive behavior. However, mild to severe hearing loss places young children with no additional disabilities or neurocognitive impairments at risk for language delays. Although the children who are HH demonstrated no more emotional or behavioral problems than their same-age peers with NH, results suggest that language delays increase their vulnerability for delays in various aspects of social competence.
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    Treatment Outcomes of Type 1 Thyroplasty Using Gore-Tex® Following Injection Laryngoplasty
    (Sage, 2023-08) Brake, Daniela A.; Patel, Rita R.; Risser, Rebecca M.; Ambrose, Gabrielle; Anthony, Benjamin P.; Otolaryngology Head & Neck Surgery, School of Medicine
    Objective: To compare voice-related outcomes of type 1 thyroplasty using Gore-Tex® between patients with and without augmentation injection laryngoplasty (IL) prior to surgery. Methods: Forty-five patients who underwent Gore-Tex® thyroplasty at a single institution by a single surgeon between November 2016 and February 2019 were identified as those who previously had IL (n = 20) and those without IL (n = 25). Pre- and post-operative voice-related primary outcomes were evaluated using the GRBAS, and CAPE-V auditory-perceptual rating scales and secondary outcome were evaluated using the VRQOL. Pre- and post-operative voice samples were blinded, randomized, and analyzed by 3 voice-specialized speech pathologists to obtain CAPE-V scores. The VRQOL and GRBAS scores were obtained from retrospective chart review. Student’s t test with a paired one-tailed distribution was used for comparisons within groups and 2-sample equal variance for comparisons between groups. Intraclass correlation coefficient determined interrater agreement. Results: GRBAS, and VRQOL significantly improved post Gore-Tex® thyroplasty. There was no difference in improvement between patients who received pre-surgery IL and those who did not in either GRBAS or VRQOL scores, but CAPE-V showed significant improvement in the IL group. A strongly positive correlation was demonstrated between the severity of CAPE-V pre-op score and the overall improvement following surgery for both groups combined. Conclusion: Patients with vocal fold paralysis have a significantly better voice after Gore-Tex® thyroplasty by self-report (VRQOL) and assessment by trained voice professionals (GRBAS). Having IL prior to surgery does not adversely affect later surgical outcomes. This paper represents one of the largest analyses of voice quality outcomes of Gore-Tex® thyroplasty using validated patient scales and randomized blinded analyses.
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    Higher glucose availability augments the metabolic responses of the C2C12 myotubes to exercise-like electrical pulse stimulation
    (American Physiological Society, 2021) Lautaoja, Juulia H.; O'Connell, Thomas M.; Mäntyselkä, Sakari; Peräkylä, Juuli; Kainulainen, Heikki; Pekkala, Satu; Permi, Perttu; Hulmi, Juha J.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    The application of exercise-like electrical pulse simulation (EL-EPS) has become a widely used exercise mimetic in vitro. EL-EPS produces similar physiological responses as in vivo exercise, while less is known about the detailed metabolic effects. Routinely, the C2C12 myotubes are cultured in high-glucose medium (4.5 g/L), which may alter EL-EPS responses. In this study, we evaluate the metabolic effects of EL-EPS under the high- and low-glucose (1.0 g/L) conditions to understand how substrate availability affects the myotube response to EL-EPS. The C2C12 myotube, media, and cell-free media metabolites were analyzed using untargeted nuclear magnetic resonance (NMR)-based metabolomics. Furthermore, translational and metabolic changes and possible exerkine effects were analyzed. EL-EPS enhanced substrate utilization as well as production and secretion of lactate, acetate, 3-hydroxybutyrate, and branched-chain fatty acids (BCFAs). The increase in BCFAs correlated with branched-chain amino acids (BCAAs) and BCFAs were strongly decreased when myotubes were cultured without BCAAs suggesting the action of acyl-CoA thioesterases on BCAA catabolites. Notably, not all EL-EPS responses were augmented by high glucose because EL-EPS increased phosphorylated c-Jun N-terminal kinase and interleukin-6 secretion independent of glucose availability. Administration of acetate and EL-EPS conditioned media on HepG2 hepatocytes had no adverse effects on lipolysis or triacylglycerol content. Our results demonstrate that unlike in cell-free media, the C2C12 myotube and media metabolites were affected by EL-EPS, particularly under high-glucose condition suggesting that media composition should be considered in future EL-EPS studies. Furthermore, acetate and BCFAs were identified as putative exerkines warranting more research. NEW & NOTEWORTHY: The present study examined for the first time the metabolome of 1) C2C12 myotubes, 2) their growth media, and 3) cell-free media after exercise-like electrical pulse stimulation under distinct nutritional loads. We report that myotubes grown under high-glucose conditions had greater responsiveness to EL-EPS when compared with lower glucose availability conditions and increased media content of acetate and branched-chain fatty acids suggests they might act as putative exerkines warranting further research.
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    Unraveling the role of the microbiome in chronic rhinosinusitis
    (Elsevier, 2022) Psaltis, Alkis J.; Wagner Mackenzie, Brett; Cope, Emily K.; Ramakrishnan, Vijay R.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Chronic rhinosinusitis (CRS) is a complex, heterogenous condition that is likely associated with infectious and inflammatory causative factors. Renewed interest in the role that microbes play in this condition has stemmed from advancements in microbe identification and parallel research implicating the microbiome as having a role in other chronic inflammatory conditions. This clinical commentary provides a review of the current literature relevant to chronic rhinosinusitis. Particular focus is placed on factors specific to investigation of the sinonasal microbiome, evidence for the role of dysbiosis in the disease state, and influences that may affect the microbiome. Possible mechanisms of disease and therapeutic implications through microbial manipulation are also reviewed, as are deficiencies and limitations of the current body of research.
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    Recognizing spoken words in semantically-anomalous sentences: Effects of executive control in early-implanted deaf children with cochlear implants
    (Taylor & Francis, 2021) Pisoni, David B.; Kronenberger, William G.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    To investigate differences in speech, language, and neurocognitive functioning in normal hearing (NH) children and deaf children with cochlear implants (CIs) using anomalous sentences. Anomalous sentences block the use of downstream predictive coding during speech recognition, allowing for investigation of rapid phonological coding and executive functioning. Methods: Extreme groups were extracted from samples of children with CIs and NH peers (ages 9 to 17) based on the 7 highest and 7 lowest scores on the Harvard-Anomalous sentence test (Harvard-A). The four groups were compared on measures of speech, language, and neurocognitive functioning. Results: The 7 highest-scoring CI users and the 7 lowest-scoring NH peers did not differ in Harvard-A scores but did differ significantly on measures of neurocognitive functioning. Compared to low-performing NH peers, high performing children with CIs had significantly lower nonword repetition scores but higher nonverbal IQ scores, greater verbal WM capacity, and excellent EF skills related to inhibition, shifting attention/mental flexibility and working memory updating. Discussion: High performing deaf children with CIs are able to compensate for their sensory deficits and weaknesses in automatic phonological coding of speech by engaging in a slow effortful mode of information processing involving inhibition, working memory and executive functioning.
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    Verbal Working Memory Error Patterns and Speech-Language Outcomes in Youth With Cochlear Implants
    (American Speech-Language-Hearing Association, 2021) Romano, Daniel R.; Kronenberger, William G.; Henning, Shirley C.; Montgomery, Caitlin J.; Ditmars, Allison M.; Johnson, Courtney A.; Bozell, Hannah D.; Yates, Adeline D.; Pisoni, David B.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Purpose: Verbal working memory (VWM) delays are commonly found in prelingually deaf youth with cochlear implants (CIs), albeit with considerable interindividual variability. However, little is known about the neurocognitive information-processing mechanisms underlying these delays and how these mechanisms relate to spoken language outcomes. The goal of this study was to use error analysis of the letter-number sequencing (LNS) task to test the hypothesis that VWM delays in CI users are due, in part, to fragile, underspecified phonological representations in short-term memory. Method: Fifty-one CI users aged 7-22 years and 53 normal hearing (NH) peers completed a battery of speech, language, and neurocognitive tests. LNS raw scores and error profiles were compared between samples, and a hierarchical regression model was used to test for associations with measures of speech, language, and hearing. Results: Youth with CIs scored lower on the LNS test than NH peers and committed a significantly higher number of errors involving phonological confusions (recalling an incorrect letter/digit in place of a phonologically similar one). More phonological errors were associated with poorer performance on measures of nonword repetition and following spoken directions but not with hearing quality. Conclusions: Study findings support the hypothesis that poorer VWM in deaf children with CIs is due, in part, to fragile, underspecified phonological representations in short-term/working memory, which underlie spoken language delays. Programs aimed at strengthening phonological representations may improve VWM and spoken language outcomes in CI users.
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    Deafness-in-a-dish: modeling hereditary deafness with inner ear organoids
    (Springer, 2022) Romano, Daniel R.; Hashino, Eri; Nelson, Rick F.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Sensorineural hearing loss (SNHL) is a major cause of functional disability in both the developed and developing world. While hearing aids and cochlear implants provide significant benefit to many with SNHL, neither targets the cellular and molecular dysfunction that ultimately underlies SNHL. The successful development of more targeted approaches, such as growth factor, stem cell, and gene therapies, will require a yet deeper understanding of the underlying molecular mechanisms of human hearing and deafness. Unfortunately, the human inner ear cannot be biopsied without causing significant, irreversible damage to the hearing or balance organ. Thus, much of our current understanding of the cellular and molecular biology of human deafness, and of the human auditory system more broadly, has been inferred from observational and experimental studies in animal models, each of which has its own advantages and limitations. In 2013, researchers described a protocol for the generation of inner ear organoids from pluripotent stem cells (PSCs), which could serve as scalable, high-fidelity alternatives to animal models. Here, we discuss the advantages and limitations of conventional models of the human auditory system, describe the generation and characteristics of PSC-derived inner ear organoids, and discuss several strategies and recent attempts to model hereditary deafness in vitro. Finally, we suggest and discuss several focus areas for the further, intensive characterization of inner ear organoids and discuss the translational applications of these novel models of the human inner ear.