Faculty Bibliography

Hypoglossal nerve stimulation (HGNS) has evolved as a novel and effective therapy for patients with moderate-to-severe obstructive sleep apnea (OSA). Despite positive published outcomes of HGNS, there exist uncertainties regarding proper patient selection, surgical technique, and the reporting of outcomes and individual factors that impact therapy effectiveness. According to current guidelines, this therapy is indicated for select patients, and recommendations are based on the Stimulation Therapy for Apnea Reduction (STAR) trial. Ongoing research and physician experiences continuously improve methods to optimize the therapy. An understanding of the way in which airway anatomy, OSA phenotypes, individual health status, psychological conditions and comorbid sleep disorders influence the effectiveness of HGNS is essential to improve outcomes and expand therapy indications. This manuscript presents discussions on current evidence, future directions, and research gaps for HGNS therapy from the 10th International Surgical Sleep Society expert research panel.

PURPOSE:), whereas no molecularly based stratification exists for the broad spectrum of patients with low- and intermediate-risk meningioma. METHODS:DNA methylation data and copy-number information were generated for 3,031 meningiomas (2,868 patients), and mutation data for 858 samples. DNA methylation subgroups, copy-number variations (CNVs), mutations, and WHO grading were analyzed. Prediction power for outcome was assessed in a retrospective cohort of 514 patients, validated on a retrospective cohort of 184, and on a prospective cohort of 287 multicenter cases. RESULTS:= .005). Besides the overall stratification advantage, the integrated score separates more precisely for risk of progression at the diagnostically challenging interface of WHO grade 1 and grade 2 tumors (hazard ratio 4.34 [2.48-7.57] and 3.34 [1.28-8.72] retrospective and prospective validation cohorts, respectively). CONCLUSION:Merging these layers of histologic and molecular data into an integrated, three-tiered score significantly improves the precision in meningioma stratification. Implementation into diagnostic routine informs clinical decision making for patients with meningioma on the basis of robust outcome prediction.

PURPOSE:No standard treatment exists for platinum-refractory, recurrent/metastatic nasopharyngeal cancer (NPC). This phase II study (NCT02605967) evaluated progression-free survival (PFS) of spartalizumab, an antiprogrammed cell death protein-1 (PD-1) monoclonal antibody, versus chemotherapy, in NPC. PATIENTS AND METHODS:Patients with nonkeratinizing recurrent/metastatic NPC who progressed on/after platinum-based chemotherapy were enrolled. Spartalizumab was dosed 400 mg once every 4 weeks, and chemotherapy was received per investigator's choice. RESULTS:gene expression. CONCLUSIONS:Spartalizumab demonstrated a safety profile consistent with other anti-PD-1 antibodies. The primary endpoint of median PFS was not met; however, median overall survival and median duration of response were longer with spartalizumab compared with chemotherapy.

HYPOTHESIS/OBJECTIVE:This study tests the hypothesis that it is possible to find tone or noise vocoders that sound similar and result in similar speech perception scores to a cochlear implant (CI). This would validate the use of such vocoders as acoustic models of CIs. We further hypothesize that those valid acoustic models will require a personalized amount of frequency mismatch between input filters and output tones or noise bands. BACKGROUND:Noise or tone vocoders have been used as acoustic models of CIs in hundreds of publications but have never been convincingly validated. METHODS:Acoustic models were evaluated by single-sided deaf CI users who compared what they heard with the CI in one ear to what they heard with the acoustic model in the other ear. We evaluated frequency-matched models (both all-channel and 6-channel models, both tone and noise vocoders) as well as self-selected models that included an individualized level of frequency mismatch. RESULTS:Self-selected acoustic models resulted in similar levels of speech perception and similar perceptual quality as the CI. These models also matched the CI in terms of perceived intelligibility, harshness, and pleasantness. CONCLUSION/CONCLUSIONS:Valid acoustic models of CIs exist, but they are different from the models most widely used in the literature. Individual amounts of frequency mismatch may be required to optimize the validity of the model. This may be related to the basalward frequency mismatch experienced by postlingually deaf patients after cochlear implantation.

OBJECTIVE:Carbonation as a sensory enhancement strategy for prevention of aspiration of thin liquids has not been thoroughly studied. The aim of our study was to examine the effect of carbonation on penetration-aspiration and pharyngeal residue in dysphagia patients using Fiber-Optic Endoscopic Evaluation of Swallowing (FEES) and to identify parameters associated with a response to carbonation. METHODS:A cross-sectional study of patients undergoing FEES in a dysphagia clinic. Patients were offered 100 cc of dyed water. Penetration-aspiration was scored using the penetration-aspiration scale (PAS). Residue was scored using the Yale Pharyngeal Residue Severity Rating Scale (YPR-SRS). Patients with a PAS ≥ 2 for water were subsequently offered 100 cc of carbonated water. PAS, YPR-SRS and residue clearance were compared between thin and carbonated liquids. Multivariate logistic regression analysis was used to identify predictors for good response to carbonation. RESULTS:84 patients were enrolled, 77.4% males, with diverse dysphagia etiologies (58.3% neurogenic, 11.9% radiation-induced, 23.8% deconditioning-induced, and 6% neck surgery induced). Median PAS was 7 (IQR 4-8) for thin liquids and 4.5 (IQR 2-8) for carbonated liquids (P = 0.0001). YPR-SRS was reduced for carbonated compared to thin liquids in the vallecula (1.58 ± 0.83 vs 1.76 ± 0.93, P = 0.001) and piriform sinuses (1.5 ± 0.87 vs 1.67 ± 0.9, P = 0.002). 31 patients had improvement in PAS with carbonation. Deconditioning as a dysphagia etiology was found to predict good response to carbonation on multivariate logistic regression analysis. CONCLUSION/CONCLUSIONS:Carbonation may prevent aspiration and improve residue management for some patients with dysphagia for liquids. LEVEL OF EVIDENCE/METHODS:IV.

BACKGROUND:TDP-43 pathology is linked to cognitive deficits in diverse neurodegenerative disorders, including frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD). The effects of TDP-43 pathology in different cell types, including astrocytes, are not clear. METHOD/METHODS:In this study, we used postmortem human brain samples, extensive behavioral testing in numerous cohorts of doubly transgenic mice, gene profiling in different isolated brain regions and cells, glial-neuronal co-culture assays and physiology, and biochemical assays to identify specific signaling cascades linked to TDP-43. RESULT/RESULTS:Our results show that astrocytic TDP-43 is mislocalized in postmortem human hippocampal tissue from AD cases. To assess the effects of widespread or hippocampus specific dysregulation of astrocytic TDP-43 in complementary systems, we generated three novel astrocyte specific mouse models of TDP-43 dysfunction. Consistently, these mouse models indicated that astrocytic TDP-43 dysfunction causes progressive hippocampus-dependent memory loss, but not motor deficits. Manipulation of astrocytic TDP-43 also increased hippocampal levels of interferon -inducible chemokines CXCL9 and CXCL10, and altered cell-autonomous antiviral signaling and defense against viral pathogens. Moreover, expression of CXCR3, the shared receptor for CXCL9 and CXCL10, was increased selectively in hippocampal presynaptic terminals. Acute or chronic stimulation of presynaptic CXCR3 modulated neuronal activities and presynaptic vesicles. CONCLUSION/CONCLUSIONS:Overall, our findings shed new light on TDP-43 dysregulation in astrocytes and its potential contributions to disease-related impairments in cognitive and immune-related functions. We report a novel chemokine-mediated astrocytic-neuronal pathway that is likely downstream of aberrant antiviral immune signaling in astrocytes that affects presynaptic release and neuronal activities. Together, these results implicate astrocytic TDP-43 dysregulation in the pathogenesis of dementia and point to chemokine signaling and CXCR3 as potential therapeutic targets for alleviating cognitive decline.

OBJECTIVE:To review our hearing preservation rates and speech recognition outcomes in patients undergoing cochlear implantation with a recently developed lateral wall electrode. STUDY DESIGN/METHODS:Retrospective cohort study. METHODS:Retrospective case series of all patients, both pediatric and adult, undergoing cochlear implantation with the Advanced Bionics Hifocus™ SlimJ electrode between December 2017 and January 2020. Main outcomes included hearing preservation rates using several definitions, speech recognition testing primarily through Arizona Biosciences (AzBio) and Consonant-Nucleus-Consonant (CNC) testing, intra- and postoperative complications. RESULTS:Sixty-one ears underwent implantation with the new electrode. Hearing preservation rates were 13.0% to 36.0% depending on the definition used. Speech recognition testing showed significant increases from pre- to postoperative condition (Implant-only AzBio: 24.1 to 48.3, P = .004, binaural AzBio: 46.1 to 65.9, P = .002, Implant-only CNC: 9.7 to 35.1, P < .001, binaural CNC: 29.8 to 59.40, P < .001) with last speech recognition testing occurring an average of 8.8 months postoperatively. The elderly population had the worst hearing preservation rates across all definitions. Five explantations were required due to two infections and three device failures. CONCLUSION/CONCLUSIONS:Hearing preservation rates varied significantly depending on the definition used, but users experienced a significant improvement in speech recognition testing after implantation. More work is needed in the community to standardize the definition of residual hearing and hearing preservation. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2021.

OBJECTIVE:The role of sclerotherapy for vascular lesions of the head and neck is well established. However, the efficacy of sclerotherapy for benign cystic lesions of the head and neck is less clear. The objective of this review is to determine the efficacy and safety of sclerotherapy for benign cystic lesions of the head and neck. DATA SOURCES:PubMed/MEDLINE, Cochrane Library, and Embase. REVIEW METHODS:The PRISMA guidelines (Preferred Reporting Systems for Systematic Reviews and Meta-analyses) were followed for this systematic review. Studies of patients with benign head and neck cystic masses treated primarily with sclerotherapy were included. Thirty-two studies met criteria for inclusion. RESULTS:= .015). Fifty-three cases (11.2%) required further surgical management. One case of laryngeal edema was reported and managed nonoperatively. CONCLUSION:Sclerotherapy appears to be a safe and efficacious option for benign cystic lesions if malignancy is reliably excluded. Efficacy rates are comparable to those of sclerotherapy for vascular malformations. The rate of serious complications is low, with 1 incident of airway edema reported in the literature.