Faculty Bibliography

Recurrent episodes of neurological dysfunction and white matter lesions in a young adult raise suspicion for multiple sclerosis (MS). However, occlusive retinopathy, hearing loss and absence of CSF oligoclonal bands are atypical for MS and should make the clinician consider an alternative diagnosis. We describe a man with hearing loss, visual signs and symptoms, and an accumulating burden of brain lesions, who was treated for a clinical diagnosis of MS for nearly two decades. Genetic testing revealed a unifying diagnosis.

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.

BACKGROUND:The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide. AIMS/OBJECTIVE:We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy (MT), stroke, and intracranial hemorrhage (ICH) hospitalizations over a 3-month period at the height of the pandemic (March 1 to May 31, 2020) compared with two control 3-month periods (immediately preceding and one year prior). METHODS:Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers. RESULTS:The hospitalization volumes for any stroke, ICH, and MT were 26,699, 4,002, and 5,191 in the 3 months immediately before versus 21,576, 3,540, and 4,533 during the first 3 pandemic months, representing declines of 19.2% (95%CI,-19.7 to -18.7), 11.5% (95%CI,-12.6 to -10.6), and 12.7% (95%CI,-13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/MT centers. High-volume COVID-19 centers (-20.5%) had greater declines in MT volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p<0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions. CONCLUSION/CONCLUSIONS:The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, MT procedures, and ICH admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/MT volumes.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To determine the association between findings of blinded reviews of preoperative drug-induced sleep endoscopy (DISE) and outcomes of hypoglossal nerve stimulation (HNS) for obstructive sleep apnea (OSA). STUDY DESIGN/METHODS:Cohort study. METHODS:A retrospective, multicenter cohort study of 343 adults who underwent treatment of OSA with HNS from 10 academic medical centers was performed. Preoperative DISE videos were scored by four blinded reviewers using the VOTE Classification and evaluation of a possible primary structure contributing to airway obstruction. Consensus DISE findings were examined for an association with surgical outcomes based on therapy titration polysomnogram (tPSG). Treatment response was defined by a decrease of ≥50% in the apnea-hypopnea index (AHI) to <15 events/hour. RESULTS:. AHI decreased (35.6 ± 15.2 to 11.0 ± 14.1 events/hour; P < .001) on the tPSG, with a 72.6% response rate. Complete palate obstruction (vs. none) was associated with the greatest difference in AHI improvement (-26.8 ± 14.9 vs. -19.2 ± 12.8, P = .02). Complete (vs. partial/none) tongue-related obstruction was associated with increased odds of treatment response (78% vs. 68%, P = .043). Complete (vs. partial/none) oropharyngeal lateral wall-related obstruction was associated with lower odds of surgical response (58% vs. 74%, P = .042). CONCLUSIONS:The DISE finding of primary tongue contribution to airway obstruction was associated with better outcomes, whereas the opposite was true for the oropharyngeal lateral walls. This study suggests that the role for DISE in counseling candidates for HNS extends beyond solely for excluding complete concentric collapse related to the velum. LEVEL OF EVIDENCE/METHODS:3 Laryngoscope, 2021.

The reasons why clinical outcomes with auditory brainstem implants (ABIs) are generally poorer than with cochlear implants (CIs) are still somewhat elusive. Prior work has focused on differences in processing of spectral information due to possibly poorer tonotopic representation and higher channel interaction with ABIs than with CIs. In contrast, this study examines the hypothesis that a potential contributing reason for poor speech perception in ABI users may be the relative lack of temporal responsiveness of the primary neurons that are stimulated by the ABI. The cochlear nucleus, the site of ABI stimulation, consists of different neuron types, most of which have much more complex responses than the auditory nerve neurons stimulated by a CI. Temporal responsiveness of primary stimulated neurons was assessed in a group of ABI and CI users by measuring recovery of electrically evoked compound action potentials (ECAPs) from single-pulse forward masking. Slower ECAP recovery tended to be associated with poorer hearing outcomes in both groups. ABI subjects with the longest recovery time had no speech understanding or even no hearing sensation with their ABI device; speech perception for the one CI outlier with long ECAP recovery time was well below average. To the extent that ECAP recovery measures reveal temporal properties of the primary neurons that receive direct stimulation form neural prosthesis devices, they may provide a physiological underpinning for clinical outcomes of auditory implants. ECAP recovery measures may be used to determine which portions of the cochlear nucleus to stimulate, and possibly allow us to enhance the stimulation paradigms.

OBJECTIVES/OBJECTIVE:To describe patterns of primary surgical treatments in patients with T4b oral cavity squamous cell carcinoma (OCSCC). STUDY DESIGN/METHODS:Historical cohort study. SETTING/METHODS:National Cancer Database. METHODS:Review of the National Cancer Database between 2004 and 2017 for all T4b OCSCCs. Only patients with curative treatment methods were included in the survival analysis. Surgical and nonsurgical outcomes were compared by multivariable and propensity score matching analysis. RESULTS:= .20). CONCLUSIONS:A minority of patients with T4b OCSCC undergo treatments with curative intent. A subset of patients underwent primary surgical treatment, which was associated with longer survival. The T4b classification might entail a heterogenous group, and further studies in revision of this classification might be justified.

PIM1 is a serine/threonine kinase that promotes and maintains prostate tumorigenesis. While PIM1 protein levels are elevated in prostate cancer relative to local disease, the mechanisms by which PIM1 contributes to oncogenesis have not been fully elucidated. Here, we performed a direct, unbiased chemical genetic screen to identify PIM1 substrates in prostate cancer cells. The PIM1 substrates we identified were involved in a variety of oncogenic processes, and included N-Myc Downstream-Regulated Gene 1 (NDRG1), which has reported roles in suppressing cancer cell invasion and metastasis. NDRG1 is phosphorylated by PIM1 at serine 330 (pS330), and the level of NDRG1 pS330 is associated higher grade prostate tumors. We have shown that PIM1 phosphorylation of NDRG1 at S330 reduced its stability, nuclear localization, and interaction with AR, resulting in enhanced cell migration and invasion.

OBJECTIVE:To develop an expert consensus statement on pediatric drug-induced sleep endoscopy (DISE) that clarifies controversies and offers opportunities for quality improvement. Pediatric DISE was defined as flexible endoscopy to examine the upper airway of a child with obstructive sleep apnea who is sedated and asleep. METHODS:Development group members with expertise in pediatric DISE followed established guidelines for developing consensus statements. A search strategist systematically reviewed the literature, and the best available evidence was used to compose consensus statements regarding DISE in children 0 to 18 years old. Topics with significant practice variation and those that would improve the quality of patient care were prioritized. RESULTS:The development group identified 59 candidate consensus statements, based on 50 initial proposed topics, that focused on addressing the following high-yield topics: (1) indications and utility, (2) protocol, (3) optimal sedation, (4) grading and interpretation, (5) complications and safety, and (6) outcomes for DISE-directed surgery. After 2 iterations of the Delphi survey and removal of duplicative statements, 26 statements met the criteria for consensus; 11 statements were designated as no consensus. Several areas, such as the role of DISE at the time of adenotonsillectomy, were identified as needing further research. CONCLUSION/CONCLUSIONS:Expert consensus was achieved for 26 statements pertaining to indications, protocol, and outcomes for pediatric DISE. Clinicians can use these statements to improve quality of care, inform policy and protocols, and identify areas of uncertainty. Future research, ideally randomized controlled trials, is warranted to address additional controversies related to pediatric DISE.

BACKGROUND:The misuse and abuse of opioids, including overprescription, has led to the current opioid epidemic and national crisis. There is a national effort to eliminate the unnecessary prescription of opioids for analgesia. METHODS:Seventy patients were randomized to receive postoperative analgesia with either 5 mg hydrocodone with 325 mg acetaminophen (opioid control group) or 400 mg of ibuprofen [nonsteroidal antiinflammatory drug (NSAID) experimental group]. Pain levels were assessed on postoperative days 1, 2, and 7. Outcome measures included numeric pain rating scores and assessments of frequency and amount of analgesic used. RESULTS:There was no significant difference in gender (p = 0.81) or age (p = 0.61) between groups. On postoperative day 0, the NSAID group (mean ± SD, 2.54 ± 1.57) was found to be noninferior to the opioid group (mean ± SD, 3.14 ± 1.75; p = 0.003). On postoperative day 1, the NSAID group showed a lower mean pain score (mean ± SD, 1.84 ± 1.29) than the opioid group (mean ± SD, 2.46 ± 1.90; p = 0.01). However, on postoperative day 7, the difference in pain scores between the NSAID (mean ± SD, 3.29 ± 2.14) and opioid (mean ± SD, 3.14 ± 2.12; p = 0.17) groups lost statistical significance. There was no significant difference in mean day of medication cessation between the NSAID (mean ± SD, 4.73 ± 1.57) and opioid (mean ± SD, 4.28 ± 2.23; p = 0.26) groups. Seventy-six percent of patients who were prescribed opioids took fewer than eight tablets. Five patients escalated from NSAIDs to opioids. There were no adverse effects related to NSAID use. CONCLUSIONS:NSAIDs are an acceptable and safe alternative to opioids for postoperative analgesia in rhinoplasty and potentially lead to better overall pain control in some patients. Significantly reducing or eliminating opioid prescriptions may be considered in light of the current opioid epidemic. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Therapeutic, II.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Vocal fold fibrosis remains a significant clinical challenge. Estrogens, steroid hormones predominantly responsible for secondary sexual characteristics in women, have been shown to alter wound healing and limit fibrosis, but the effects on vocal fold fibrosis are unknown. We sought to elucidate the expression of estrogen receptors and the effects of estrogens on TGF-β1 signaling in rat vocal fold fibroblasts (VFFs). STUDY DESIGN/METHODS:In vitro. METHODS: M) were employed as antagonists of ERα or GPR30, respectively. qPCR was employed to determine estrogen receptor-mediated effects of E2 on genes related to fibrosis. RESULTS: M) and TGF-β1 significantly increased Smad7 (P = .03) and decreased Col1a1 (P = .04) compared to TGF-β1 alone; this response was negated by the combination of ICI and G36 (P = .009). CONCLUSIONS:E2 regulated TGF-β1/Smad signaling via estrogen receptors in VFFs. These findings provide insight into potential mechanisms of estrogens on vocal fold injury with the goal of enhanced therapeutics for vocal fold fibrosis. LEVEL OF EVIDENCE/METHODS:NA. Laryngoscope, 2020.