Faculty Bibliography

OBJECTIVE:Laryngopharyngeal and Gastroesophageal reflux (LPR and GER) are distinct clinical entities that present with a range of non-specific symptoms. The exact prevalence in the pediatric population is unknown. While there has been an increase in the use of PPIs, lack of clear guidelines, conflicting evidence regarding efficacy and safety concerns with long-term use require physicians to use their own anecdotal experience and clinical judgement when treating patients. The goal of this study was to evaluate practice patterns among pediatric otolaryngologists regarding the use of proton-pump inhibitors for reflux-related conditions. METHODS:A survey was submitted to American Society of Pediatric Otolaryngology (ASPO) members to determine practice patterns regarding use of PPIs for reflux-related conditions in the newborn and infant population. Statistical analysis using Fisher's exact test was performed. RESULTS:37% of respondents would not prescribe PO PPIs in neonates, with 50% not prescribing IV PPIs. 60% would prescribe a PPI as second or third-line treatment for infants (10 weeks to 1-year). Only 10% would prescribe as first-line in this age group. 48% would prescribe PPIs once daily and 19% as BID. No significant practice differences exist based on years of experience, number of relevant patients seen, and setting of practice. CONCLUSION/CONCLUSIONS:There was no agreement regarding dosage, frequency and duration of PPI treatment for reflux disease in neonates and infants. There was also no correlation with experience or practice setting. This emphasizes the need for a multidisciplinary approach and consensus statement to guide management of GER and LPR in this population.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Upper airway stimulation for obstructive sleep apnea (OSA) via implantable hypoglossal nerve stimulation (HGNS) reduces airway obstruction by selectively stimulating nerve fibers that innervate muscles that produce tongue protrusion, while avoiding fibers that produce tongue retraction. This selective stimulation likely depends upon the location, intensity, and type of electrical stimulation delivered. This study investigates the impact of changing stimulation parameters on tongue muscle activation during HGNS using intraoperative nerve integrity monitoring in conjunction with electromyography (EMG). STUDY DESIGN/METHODS:Prospective case series. METHODS:Ten patients undergoing unilateral HGNS implantation for OSA in a university hospital setting were studied. Data included EMG responses in tongue muscles that produce protrusion (genioglossus), retraction (styloglossus/hyoglossus), and stiffening (transverse/vertical) in response to intraoperative bipolar probe electrical stimulation of lateral and medial branches of the hypoglossal nerve (HGN) and to implantable pulse generator (IPG) unipolar and bipolar settings after placement of the stimulation cuff. RESULTS:Stimulation of medial division HGN branches resulted in EMG responses in genioglossus muscles, but not in styloglossus/hyoglossus muscles, whereas stimulation of the lateral division HGN branches drove responses in styloglossus/hyoglossus muscles. Variable responses in transverse/vertical muscles were observed with stimulation of lateral and medial division branches. After electrode cuff placement, unipolar and bipolar HGN stimulation configurations of IPG resulted in unique patterns of muscle activation. CONCLUSIONS:The relative activation of extrinsic and intrinsic tongue musculature by HGNS is determined by stimulus location, intensity, and type. Intraoperative neurophysiological monitoring of tongue muscle activation enables proper electrode cuff placement and may provide essential data for stimulus optimization. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2019.

OBJECTIVE:To evaluate the performance changes after sequential bilateral cochlear implantation in a pediatric population of bimodal cochlear implant (CI) users. To evaluate the factors which influence the parental and recipient decision to discontinue hearing aid use and seek a second implant. STUDY DESIGN/METHODS:Retrospective case review, within-subject comparison. SETTING/METHODS:Tertiary referral center. PATIENTS/METHODS:Thirty-one pediatric (<18 yr) bimodal CI users who underwent sequential bilateral CI. INTERVENTIONS/METHODS:Sequential bilateral CI. MAIN OUTCOME MEASURES/METHODS:Parental and/or recipient's reasons for discontinuing their hearing aid and pursuing a second implant, device usage from datalogs, speech understanding in the bimodal and bilateral CI condition. RESULTS:Parents/patients were motivated to pursue sequential bilateral CI based on their positive performance with CI1, the expectation of further improvement with a second CI, and the prospect of having a second independently functional ear. In the bimodal condition, mean word recognition score (WRS), sentence recognition in quiet (SIQ), and sentence recognition in noise (SIN) scores were 87.4, 97.3, and 92.9% respectively. At 1-year post-sequential bilateral CI, the mean WRS, SIQ, and SIN score were 92.7, 98.7, and 97.7%, respectively. The improvement in bilateral CI speech scores compared with bimodal scores was statistically significant for WRS (p = 0.015). A ceiling effect limited the ability to detect further meaningful differences on speech perception testing. CONCLUSIONS:The bilateral CI condition demonstrates equivalent or slightly superior performance compared with the bimodal condition. Several non-speech benefits were elicited from parents as reasons for pursuing a second implant. Close monitoring of the residual acoustic hearing, inquiring about the perceived benefits provided by the HA, and early counseling regarding the potential for sequential bilateral CI are important aspects in determining if and when a second implant is indicated.

Infant high grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histological review, methylation profiling, custom panel and genome/exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an 'intrinsic' spectrum of disease specific to the infant population. These included those with targetable MAP-kinase alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n=31), NTRK1/2/3 (n=21), ROS1 (n=9) and MET (n=4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly supports the concept that infant gliomas require a change in diagnostic practice and management.

BACKGROUND:The COVID-19 pandemic has significantly impacted medical training. Here we assess its effect on head and neck surgical education. METHODS:Surveys were sent to current accredited program directors and trainees to assess the impact of COVID-19 on the fellow's experience and employment search. Current fellows' operative logs were compared with those of the 2018 to 2019 graduates. RESULTS:Despite reduction in operative volume, 82% of current American Head and Neck Society fellows have reached the number of major surgical operations to support certification. When surveyed, 86% of program directors deemed their fellow ready to enter practice. The majority of fellows felt prepared to practice ablative (96%), and microvascular surgery (73%), and 57% have secured employment to follow graduation. Five (10%) had a pending job position put on hold due to the pandemic. CONCLUSIONS:Despite the impact of the COVID-19 pandemic, current accredited trainees remain well-positioned to obtain proficiency and enter the work-force.

Whether G protein-coupled receptors signal from endosomes to control important pathophysiological processes and are therapeutic targets is uncertain. We report that opioids from the inflamed colon activate δ-opioid receptors (DOPr) in endosomes of nociceptors. Biopsy samples of inflamed colonic mucosa from patients and mice with colitis released opioids that activated DOPr on nociceptors to cause a sustained decrease in excitability. DOPr agonists inhibited mechanically sensitive colonic nociceptors. DOPr endocytosis and endosomal signaling by protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) pathways mediated the sustained inhibitory actions of endogenous opioids and DOPr agonists. DOPr agonists stimulated the recruitment of Gα_i/o and β-arrestin1/2 to endosomes. Analysis of compartmentalized signaling revealed a requirement of DOPr endocytosis for activation of PKC at the plasma membrane and in the cytosol and ERK in the nucleus. We explored a nanoparticle delivery strategy to evaluate whether endosomal DOPr might be a therapeutic target for pain. The DOPr agonist DADLE was coupled to a liposome shell for targeting DOPr-positive nociceptors and incorporated into a mesoporous silica core for release in the acidic and reducing endosomal environment. Nanoparticles activated DOPr at the plasma membrane, were preferentially endocytosed by DOPr-expressing cells, and were delivered to DOPr-positive early endosomes. Nanoparticles caused a long-lasting activation of DOPr in endosomes, which provided sustained inhibition of nociceptor excitability and relief from inflammatory pain. Conversely, nanoparticles containing a DOPr antagonist abolished the sustained inhibitory effects of DADLE. Thus, DOPr in endosomes is an endogenous mechanism and a therapeutic target for relief from chronic inflammatory pain.

Laryngeal videoendoscopy is one of the main tools in clinical examinations for voice disorders and voice research. Using high-speed videoendoscopy, it is possible to fully capture the vocal fold oscillations, however, processing the recordings typically involves a time-consuming segmentation of the glottal area by trained experts. Even though automatic methods have been proposed and the task is particularly suited for deep learning methods, there are no public datasets and benchmarks available to compare methods and to allow training of generalizing deep learning models. In an international collaboration of researchers from seven institutions from the EU and USA, we have created BAGLS, a large, multihospital dataset of 59,250 high-speed videoendoscopy frames with individually annotated segmentation masks. The frames are based on 640 recordings of healthy and disordered subjects that were recorded with varying technical equipment by numerous clinicians. The BAGLS dataset will allow an objective comparison of glottis segmentation methods and will enable interested researchers to train their own models and compare their methods.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

BACKGROUND:Complications from radiotherapy (RT) alone or combined with surgery and/or chemotherapy for head and neck cancer (HNC) sometimes necessitate hospitalization. Our aim was to evaluate the frequency, cause, and survival outcomes associated with hospitalizations in patients undergoing RT for HNC. PATIENTS AND METHODS/METHODS:Using a retrospective single-institution database, we reviewed hospitalization records of HNC patients treated at Roswell Park Comprehensive Cancer Center with definitive or post-operative RT between 2003 and 2017. Patients who were admitted during treatment and within 90-days post-RT were identified. Multivariate analyses, Kaplan-Meier statistics, and analysis on propensity score matching were performed to obtain matched-pair, after matching baseline characteristics, such as age, gender, smoking, tumor staging, p16 status, and treatments received. RESULTS:839 patients were eligible for analysis. Median follow-up was 34.8 months (Interquartile range [IQR] 15.6-64.8). 595 (71%) received definitive RT and 244 (29%) received adjuvant RT. Chemotherapy was used in 671 patients (80%). 171 patients (20%) had at least one hospitalization. Dehydration (40%) and fever (29%) were the most frequent causes of admission. Hospitalized patients had significantly worse overall survival (OS) (Hazards ratio [HR] 1.61, 95% CI 1.26-2.07, p < 0.001) and cancer-specific survival (CSS) (HR 1.45, 95% CI 1.07-1.95, p = 0.02). 163 matched pairs had median follow-up of 58.6 months (IQR 37.6-85.0). Median OS was 34.5 months (IQR 13.3-58.0) for hospitalized versus 44.2 months (IQR 20.3-78.7) for non-hospitalized patients (p = 0.01). CONCLUSION/CONCLUSIONS:This study reveals significantly worse OS and CSS for patients hospitalized during RT for HNC. Hospitalization may be an early marker for worse survival.