Faculty Bibliography

Most head and neck paragangliomas (PGLs) are biochemically silent and often present with recurrence and metastases in association with hereditary syndromes. Whole-body functional imaging is increasingly used to detect tumor extent and guide treatment planning of PGLs. [68Ga]-DOTATATE, which targets somatostatin receptor 2 (SSTR2) overexpression, has emerged as a sensitive functional imaging modality in PGLs. We present a patient with metastatic glomus caroticum PGL in whom [68Ga]-DOTATATE PET/MRI provided a more accurate characterization of metastatic extent, as compared to gadolinium-enhanced MRI of the neck and whole body [18F]-FDG PET/CT. We then review the current literature and discuss the imaging implications of [68Ga]-DOTATATE PET/MRI in PGLs.

ABSTRACT/UNASSIGNED:Migraine affects ∼15% of the world's population greatly diminishing their quality of life. Current preventative treatments are effective in only a subset of migraine patients, and while cannabinoids appear beneficial in alleviating migraine symptoms, central nervous system (CNS) side effects limit their widespread use. We developed peripherally-restricted cannabinoids (PRCBs) that relieve chronic pain symptoms of cancer and neuropathies, without appreciable CNS side effects or tolerance development. Here we determined PRCB effectiveness in alleviating hypersensitivity symptoms in mouse models of migraine and medication overuse headache (MOH). Chronic glyceryl trinitrate (GTN, 10 mg/kg) administration led to increased sensitivity to mechanical stimuli, and increased expression of phosphorylated protein kinase A (p-PKA), neuronal nitric oxide synthase (nNOS), and transient receptor potential ankyrin 1 (TRPA1) proteins in trigeminal ganglia. PRCB pretreatment, but not posttreatment, prevented behavioral and biochemical correlates of GTN-induced sensitization. Low pH- and allyl isothiocyanate-activated currents in acutely isolated trigeminal neurons were reversibly attenuated by PRCB application. Chronic GTN treatment significantly enhanced these currents. Chronic sumatriptan treatment also led to development of allodynia to mechanical and cold stimuli which was slowly reversible after sumatriptan discontinuation. Subsequent challenge with a previously ineffective low-dose GTN (0.1-0.3 mg/kg) revealed latent behavioral sensitization and increased expression of p-PKA, nNOS, and TRPA1 proteins in trigeminal ganglia. PRCB pretreatment prevented all behavioral and biochemical correlates of allodynia and latent sensitization. Importantly, chronic PRCB treatment alone did not produce any behavioral or biochemical signs of sensitization. These data validate peripheral cannabinoid receptors as potential therapeutic targets in migraine and MOH.

Objectives/UNASSIGNED:To describe our experience with the use of postoperative antibiotics in the management of unilateral chronic rhinosinusitis (CRS) patients with active infection at the time of surgery, and to evaluate the need for routine postoperative antibiotic administration in this population. Methods/UNASSIGNED:This retrospective chart review analyzed the medical records of all patients who underwent endoscopic sinus surgery for unilateral purulent CRS between November 2013 and September 2019 at a tertiary care center and who were not prescribed routine postoperative antibiotics. Duration of time until normalization of sinus cavities and whether antibiotics were ultimately prescribed for persistent infectious signs and symptoms were recorded. Patient characteristics and findings were analyzed to determine if any of the evaluated parameters were associated with the need for postoperative antibiotics. Results/UNASSIGNED: = .066). No evaluated variables were associated with antibiotic use on univariate or multivariate analysis. Conclusion/UNASSIGNED:Postoperative antibiotics were not necessary to normalize infected sinus cavities for nearly half of patients with unilateral purulent CRS in this series. Further studies are needed to better delineate which patients would derive benefit from postoperative antibiotics. Level of Evidence/UNASSIGNED:Level IV.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:We sought to characterize rates of progression to posterior glottic stenosis (PGS) from autoimmune or idiopathic subglottic stenosis. STUDY DESIGN/METHODS:This was a retrospective review. METHODS:Patients from a tertiary-care laryngology practice over a 10-year period with autoimmune or idiopathic subglottic stenosis (SGS) were included. Patients with a history of prolonged intubation or other causes of iatrogenic stenosis were excluded. PGS was confirmed on videostrobolaryngoscopy recordings by a fellowship-trained laryngologist. PGS type (1-4) was also recorded. Demographic information was recorded, and if applicable, autoimmune disease type was specified. Time until PGS was recorded along with the number of interventions. Chi-squared analysis was used to compare PGS in autoimmune and idiopathic SGS. RESULTS:A total of 77 patients were identified with autoimmune (32 patients) or idiopathic (45 patients) subglottic stenosis. Autoimmune pathologies included systemic lupus erythematosus, granulomatosis with polyangiitis (GPA), rheumatoid arthritis, relapsing polychondritis, and sarcoidosis, with GPA the most common (14/32). Patients with autoimmune SGS had a higher rate of PGS (10 of 32) compared to idiopathic subglottic stenosis (1 of 45) for an odds ratio of 20 (95% CI: 2.4-166.4, P = .006). Patients with idiopathic SGS were more likely to be female (all 45 compared to 29/32 autoimmune, P = .07) and older (mean 53 (range 29-75) compared to 46 (20-82), P = .02). CONCLUSIONS:In this large patient cohort, autoimmune SGS patients were found to have a higher likelihood of developing PGS compared to their idiopathic counterparts, suggesting that counseling for this progression may be warranted. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2020.

Maternal care, including by non-biological parents, is important for offspring survival^1-8. Oxytocin^1,2,9-15, which is released by the hypothalamic paraventricular nucleus (PVN), is a critical maternal hormone. In mice, oxytocin enables neuroplasticity in the auditory cortex for maternal recognition of pup distress¹⁵. However, it is unclear how initial parental experience promotes hypothalamic signalling and cortical plasticity for reliable maternal care. Here we continuously monitored the behaviour of female virgin mice co-housed with an experienced mother and litter. This documentary approach was synchronized with neural recordings from the virgin PVN, including oxytocin neurons. These cells were activated as virgins were enlisted in maternal care by experienced mothers, who shepherded virgins into the nest and demonstrated pup retrieval. Virgins visually observed maternal retrieval, which activated PVN oxytocin neurons and promoted alloparenting. Thus rodents can acquire maternal behaviour by social transmission, providing a mechanism for adapting the brains of adult caregivers to infant needs via endogenous oxytocin.

OBJECTIVES/HYPOTHESIS:To investigate the effect of a multimedia educational module on provider attitudes toward pediatric tracheostomy care. We also describe the process of module development and dissemination at an academic children's hospital. STUDY DESIGN:Prospective observational study. METHODS:The pediatric airway committee at an urban tertiary care center developed a multimedia pediatric tracheostomy care module. Nurses, respiratory therapists, as well as resident, fellow, and attending physicians caring for pediatric patients with tracheostomies were eligible. Managers and clinical supervisors from various units recruited participants to complete the pediatric tracheostomy care electronic module and pre- and postassessment knowledge quizzes and surveys. Provider confidence was analyzed using Kruskal-Wallis H-test and Mann-Whitney U-test, and paired t-test was used to compare pre- and postmodule quiz scores. RESULTS:A total of 422 participants completed the module. A total of 275 participants completed the premodule survey, 385 completed the premodule quiz, 253 completed the postmodule survey, and 233 completed the postmodule quiz. Participants included providers in the neonatal intensive care unit, pediatric intensive care unit, pediatric emergency department, and pediatric wards. Postmodule surveys demonstrated a significant reduction in the average percentage of participants indicating lack of confidence with regards to changing an established tracheostomy, responding to accidental decannulation of established tracheostomy, and responding to accidental decannulation of fresh tracheostomy (P < .001). Average quiz scores increased by 5.6 points from 83.0% to 88.6% (P < .00001). CONCLUSIONS:A multimedia educational module can improve provider perception of their knowledge and confidence surrounding pediatric tracheostomy management. LEVEL OF EVIDENCE:3 Laryngoscope, 131:1893-1901, 2021.

Undiagnosed and untreated obstructive sleep apnea (OSA) is associated with health comorbidities and negatively affects quality of life. Alternative treatments should be considered in patients who are unable to tolerate or benefit from positive airway pressure treatment. When properly indicated, positional devices, oral appliances, airway surgery, and hypoglossal nerve stimulation have been shown to be effective in treating OSA. Hypoglossal nerve stimulation is a successful second-line treatment with low associated morbidity and complication rate.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Meniere's disease (MD) is a debilitating condition characterized by hearing loss, vertigo, and tinnitus. The objective of this study was to systematically investigate outcomes in MD after cochlear implantation (CoI), with and without labyrinthectomy. STUDY DESIGN/METHODS:Systematic review and meta-analysis. METHODS:A systematic review of articles in Medline and Embase was performed to identify all studies of patients with MD who underwent CoI. This analysis evaluates outcomes of speech recognition, pure tone audiometry, vertigo, tinnitus, and quality of life. RESULTS:Of 321 studies identified, 37 were included, involving 216 patients. Mean age at implantation was 61.4 years (range 27-85 years) with average length of follow-up at 1.7 years (range 0-9 years). Forty-four (20.4%) patients underwent labyrinthectomy. Meta-analysis demonstrated significant improvements in audiometric outcomes following CoI. There was a statistically significant improvement in Hearing in Noise Test performance, with a mean difference improvement of 44.7 (95% confidence interval [CI] [8.8, 80.6]) at 6 months and 60.1 (95% CI [35.3, 85.0]) at 12 months. The Freiburger Monosyllabic Test (FMT) and Consonant-Nucleus-Consonant (CNC) also improved significantly, with mean difference improvements of 46.2 (95% CI [30.0, 62.4]) for FMT and 19.3 (95% CI [8.1, 30.4]) for CNC. There was a statistically significant decrease in tinnitus, as measured by a mean difference reduction of 48.1 (95% CI [1.0, 95.2]) in the Tinnitus Handicap Index. CONCLUSIONS:CoI with and without simultaneous labyrinthectomy is a viable treatment option for patients with MD, yielding high rates of tinnitus suppression and vertigo control. Post-CoI MD patients demonstrate similar postoperative speech perception outcomes to non-MD implant recipients. Laryngoscope, 2021.

Pain is one of the most common medical conditions and affects more Americans than diabetes, heart disease, and cancer combined. Current pain treatments mainly rely on opioid analgesics and remain unsatisfactory. The life-threatening side effects and addictive properties of opioids demand new therapeutic approaches. Nanomedicine may be able to address these challenges as it allows for sensitive and targeted treatments without some of the burdens associated with current clinical pain therapies. This review discusses the physiology of pain, the current landscape of pain treatment, novel targets for pain treatment, and recent and ongoing efforts to effectively treat pain using nanotechnology-based approaches. We highl ight advances in nanoparticle-based drug delivery to reduce side effects, gene therapy to tackle the source of pain, and nanomaterials-based scavenging to proactively mediate pain signaling.