Faculty Bibliography

OBJECTIVE:To evaluate the effect of definitive radiotherapy dose on survival in patients with human papillomavirus positive oropharyngeal carcinoma. METHODS:Human papillomavirus positive oropharyngeal carcinoma patients staged T1-3 and N0-2c, who received definitive radiotherapy (fraction sizes of 180 cGy to less than 220 cGy), were identified from the National Cancer Database 2010-2014 and stratified by radiation dose (50 Gy to less than 66 Gy, or 66 Gy or more). RESULTS:A total of 2173 patients were included, of whom 124 (6 per cent) received a radiation dose of 50 Gy to less than 66 Gy. With a median follow up of 33.8 months, patients had a 3-year overall survival rate of 88.6 per cent (95 per cent confidence interval = 87.1-90.1 per cent). On multivariate Cox analysis, a radiotherapy dose of 50 Gy to less than 66 Gy (hazard ratio = 0.95, 95 per cent confidence interval = 0.52-1.74, p = 0.86) was not a predictor of increased mortality risk. CONCLUSION/CONCLUSIONS:Human papillomavirus positive oropharyngeal carcinoma patients had excellent outcomes with definitive radiotherapy doses of 50 Gy to less than 66 Gy. These results further support patients enrolling into clinical trials for radiation dose de-escalation.

Sensory-driven decisions are formed by accumulating information over time. Although parietal cortex activity is thought to represent accumulated evidence for sensory-based decisions, recent perturbation studies in rodents and non-human primates have challenged the hypothesis that these representations actually influence behavior. Here, we asked whether the parietal cortex integrates acoustic features from auditory cortical inputs during a perceptual decision-making task. If so, we predicted that selective inactivation of this projection should impair subjects' ability to accumulate sensory evidence. We trained gerbils to perform an auditory discrimination task and obtained measures of integration time as a readout of evidence accumulation capability. Minimum integration time was calculated behaviorally as the shortest stimulus duration for which subjects could discriminate the acoustic signals. Direct pharmacological inactivation of parietal cortex increased minimum integration times, suggesting its role in the behavior. To determine the specific impact of sensory evidence, we chemogenetically inactivated the excitatory projections from auditory cortex to parietal cortex and found this was sufficient to increase minimum behavioral integration times. Our signal-detection-theory-based model accurately replicated behavioral outcomes and indicated that the deficits in task performance were plausibly explained by elevated sensory noise. Together, our findings provide causal evidence that parietal cortex plays a role in the network that integrates auditory features for perceptual judgments.

OBJECTIVES/OBJECTIVE:To evaluate the impact of the novel coronavirus pandemic on practice patterns, clinical behavior, personal health, and emotional/psychological concerns of rhinologists. METHODS:A 15-question survey was sent out to the American Rhinologic Society's (ARS) membership to determine the impact of COVID-19 during the crisis. Demographic factors and practice patterns were collected and evaluated. RESULTS:There were 224 total respondents out of 835 ARS members queried (26.8% response rate). Study queries were sent in April 2020. Notably, 17.8% reported illness in themselves or their staff and 74.4% noted a psychological/emotional impact. A plurality of rhinologists noted their practice volume and in-office procedure volume has become 20.0% and 0.0% of their prior volumes, respectively. In addition, 96.2% were noted to be using telemedicine in our subspecialty. CONCLUSION/CONCLUSIONS:In addition to severely impacting volume and the perception of future decreases in patients and revenue, the COVID-19 pandemic has had a physical and emotional impact on rhinologists in ways that need to be further studied. These data include significantly novel and objective information. The COVID-19 crisis also reveals the important role of telemedicine in rhinology. Guidelines regarding personal protective equipment for in-office visits, nasal endoscopy, and other in-office and operating room procedures would be particularly helpful as future waves are expected.

Cancer invading into nerves, termed perineural invasion (PNI), is associated with pain. Here we show that oral cancer patients with PNI report greater spontaneous pain and mechanical allodynia compared with patients without PNI, suggesting unique mechanisms drive PNI-induced pain. We studied the impact of PNI on peripheral nerve physiology and anatomy using a murine sciatic nerve PNI model. Mice with PNI exhibited spontaneous nociception and mechanical allodynia. PNI induced afterdischarge in A high threshold mechanoreceptors (AHTMRs), mechanical sensitization (i.e., decreased mechanical thresholds) in both A and C HTMRs, and mechanical desensitization in low threshold mechanoreceptors (LTMRs). PNI resulted in nerve damage, including axon loss, myelin damage, and axon degeneration. Electrophysiological evidence of nerve injury included decreased conduction velocity, and increased percentage of both mechanically-insensitive and electrically-unexcitable neurons. We conclude that PNI-induced pain is driven by nerve injury and peripheral sensitization in HTMRs.

STUDY OBJECTIVES/OBJECTIVE:The effectiveness of hypoglossal nerve stimulation (HGNS) in the treatment of obstructive sleep apnea (OSA) depends upon the selective stimulation of nerve fibers that innervate tongue muscles that produce tongue protrusion (genioglossus) and stiffening (transverse/vertical), while avoiding fibers that innervate muscles that produce tongue retraction (styloglossus/hyoglossus). Post-operative treatment failures can be related to mixed activation of retractor and protrusor muscles despite intraoperative efforts to identify and avoid nerve fibers that innervate retractor muscles. This study describes a novel intraoperative protocol that more optimally identifies mixed activation by utilizing an expanded set of stimulation/recording parameters. METHODS:Case series in a university hospital setting of patients undergoing unilateral HGNS implantation for OSA. Data included EMG responses in genioglossus and styloglossus/hyoglossus to intraoperative stimulation with an implantable pulse generator (IPG) using unipolar (---, o-o) and bipolar (+-+) settings. RESULTS:In a subset of patients (3/55), low-intensity unipolar IPG stimulation revealed significant mixed activation of styloglossus/hyoglossus and genioglossus muscles that was not evident under standard bipolar IPG stimulation conditions. Additional surgical dissection and repositioning of the electrode stimulation cuff reduced mixed activation. CONCLUSIONS:A novel intraoperative neurophysiological monitoring protocol was able to detect significant mixed activation during HGNS that was otherwise absent with standard parameters. This enabled successful electrode cuff repositioning and dramatic reduction of mixed activation.

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.

OBJECTIVE:To quantify pain and opioid use after otorhinolaryngologic surgery. To determine the effect of patient and surgical factors on primary outcomes. STUDY DESIGN/METHODS:Prospective cohort. SETTING/METHODS:Tertiary academic hospital. SUBJECTS AND METHODS/METHODS:Patients undergoing elective otorhinolaryngologic surgery were prospectively enrolled. Patients completed demographic surveys and psychometric questionnaires assessing attitudes toward pain and baseline anxiety and depression before surgery. After surgery, patients documented peak pain levels (0-100 mm, visual analog scale) and daily prescription and nonprescription analgesic requirements over a 2-week period. Average daily and cumulative pain and opioid use were calculated and compared among patient cohorts stratified by procedure and preoperative factors. RESULTS:A total of 134 patients were enrolled. Total tonsillectomy was associated with significantly higher pain scores and opioid consumption, as compared to all other procedures. There was moderate correlation between average cumulative pain and opioid use. Older patients required significantly fewer doses of opioids. There was no effect of sex, marital status, or education level on postoperative pain or opioid use. Psychometric instrument scores and chronic pain or analgesic use were not associated with significant differences in pain or opioid requirements. Most patients were prescribed substantially more opioids than they actually required. CONCLUSION/CONCLUSIONS:Postoperative pain following elective otorhinolaryngologic surgery decreases dramatically within the first week and requires only few days of opioid analgesia, with the exception of tonsillectomy. Almost all patients required fewer than 15 doses of opioids.

OBJECTIVE:To investigate differences in epidemiology of oropharyngeal squamous cell carcinoma (OPSCC) with regards to human papillomavirus (HPV), race, and socioeconomic status (SES) using the National Cancer Database (NCDB). STUDY DESIGN/METHODS:Population-based cohort study. SETTING/METHODS:Racial and socioeconomic disparities in survival of OPSCC have been previously acknowledged. However, the distribution of HPV-related cancers and its influence on survival in conjunction with race and SES remain unclear. SUBJECTS AND METHODS/METHODS:All patients with OPSCC in the NCDB with known HPV status from 2010 to 2016 were included. Differences in presentation, HPV status, treatment, and outcomes were compared along racial and socioeconomic lines. Univariable and multivariable Cox regression survival analyses were performed. RESULTS:< .001) were associated with worse survival. CONCLUSION/CONCLUSIONS:Significant differences in HPV status exist between socioeconomic and racial groups, with HPV-negative disease more common among blacks and lower SES. When controlling for HPV status, race and SES still influence outcomes in oropharyngeal cancers.

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.

Mother-infant bonding develops rapidly following parturition and is accompanied by changes in sensory perception and behavior. Here, we study how ultrasonic vocalizations (USVs) are represented in the brain of mothers. Using a mouse line that allows temporally controlled genetic access to active neurons, we find that the temporal association cortex (TeA) in mothers exhibits robust USV responses. Rabies tracing from USV-responsive neurons reveals extensive subcortical and cortical inputs into TeA. A particularly dominant cortical source of inputs is the primary auditory cortex (A1), suggesting strong A1-to-TeA connectivity. Chemogenetic silencing of USV-responsive neurons in TeA impairs auditory-driven maternal preference in a pup-retrieval assay. Furthermore, dense extracellular recordings from awake mice reveal changes of both single-neuron and population responses to USVs in TeA, improving discriminability of pup calls in mothers compared with naive females. These data indicate that TeA plays a key role in encoding and perceiving pup cries during motherhood.