Dysphagia as a predictor of voice handicap and voice restoration in unilateral vocal fold immobility.

OBJECTIVE: Dysphagia is multifactorial in unilateral vocal fold immobility (UVFI). Severe dysphagia could indicate greater functional deficits in UVFI. The purpose of this study is to evaluate the association of dysphagia with the need for surgical voice restoration in patients with UVFI. STUDY DESIGN: Retrospective chart review. SETTING: Single-institution, tertiary referral center. METHODS: Records of UVFI patients from 2008 to 2018 were examined. Dysphagia severity was extracted from patient history. Etiology of UVFI and other relevant variables were analyzed to determine their association with dysphagia. Dysphagia severity and other clinical variables were then analyzed for their association with surgical voice restoration. RESULTS: Eighty patients met selection criteria out of 478 patients with UVFI. There was significant concordance between dysphagia severity extracted from patient history and patient-reported EAT-10 scores (R = 0.59, p = 0.000035). Patients' EAT-10 scores were correlated with VHI-10 scores (R = 0.45, p = 0.011). Severe dysphagia (p = 0.037), high VHI-10 score on presentation (p = 0.0009), and longer duration of hoarseness before presentation (p = 0.008) were associated with surgical voice restoration in UVFI patients. CONCLUSION: In this pilot study, severe dysphagia and increased voice handicap on presentation were associated with the need for surgical voice restoration in UVFI patients. Presenting dysphagia may be an additional variable for clinicians to consider for management of UVFI.

Speech Discrimination Outcomes in Adult Cochlear Implant Recipients by Primary Language and Bilingual Hispanic Patients.

OBJECTIVE: Compare cochlear implant (CI) outcomes in English speakers, Spanish speakers, and bilingual Hispanics. STUDY DESIGN: Retrospective review. SETTING: Academic tertiary care center. METHODS: Eighty-five postlingually deafened adults unilaterally implanted between January 2014 and December 2018 were stratified by primary language. Primary outcomes were: (1) English consonant-nucleus-consonant and Spanish bisyllables word tests in quiet, and (2) English AzBio and Latin American Hearing In Noise Test (LA-HINT) sentence tests in quiet and in noise at multiple time-intervals postactivation. RESULTS: In the respective languages, primary Spanish speakers (n = 24), and English speakers (n = 61) experienced the greatest increases in average scores for word and sentence tests in quiet during the first 6 months postactivation, with gradual increases in average scores over time. English speakers performed significantly worse on AzBio tests in noise, compared to quiet, while the addition of noise did not significantly affect average LA-HINT scores in Spanish speakers across multiple time intervals. An early ceiling effect was also demonstrated for LA-HINT. Although not significant, bilingual Hispanics (n = 12) had lower average AzBio in quiet scores than English speakers and higher average LA-HINT in quiet scores than the Spanish speakers across multiple time intervals. CONCLUSION: English and Spanish CI users experienced the greatest increases in speech understanding in quiet the first few months after implant activation. An early ceiling effect is demonstrated with LA-HINT, indicating LA-HINT is not appropriate for evaluating longitudinal CI outcomes in Spanish speakers. Bilingual Hispanics represent a unique group, and further investigations are necessary to understand speech perception patterns in both languages and develop the best CI test strategies for these individuals.

Cytokine Profiling of Cyst Fluid and Tumor-Associated Macrophages in Cystic Vestibular Schwannoma.

BACKGROUND: The vestibular schwannoma (VS) secretome can initiate monocyte recruitment and macrophage polarization to M1 (proinflammatory) and/or M2 (protumorigenic) phenotypes, which in turn secrete additional cytokines that contribute to the tumor microenvironment. Profiling cyst fluid and cerebrospinal fluid (CSF) in cystic VS provides a unique opportunity to understand mechanisms that may contribute to tumor progression and cyst formation. HYPOTHESIS: Cystic VSs secrete high levels of cytokines into cyst fluid and express abundant M1 and M2 macrophages. METHODS: Tumor, CSF, and cyst fluid were prospectively collected from 10 cystic VS patients. Eighty cytokines were measured in fluid samples using cytokine arrays and compared with normal CSF from normal donors. Immunofluorescence was performed for CD80 + M1 and CD163 + M2 macrophage markers. Demographic, audiometric, and radiographic information was obtained through retrospective chart review. RESULTS: Cyst fluid expressed more osteopontin and monocyte chemotactic protein-1 (MCP-1; p < 0.0001), when compared with normal CSF. Cyst fluid also expressed more protein ( p = 0.0020), particularly MCP-1 ( p < 0.0001), than paired CSF from the same subjects. MCP-1 expression in cyst fluid correlated with CD80 + staining in VS tissue ( r = 0.8852; p = 0.0015) but not CD163 + staining. CONCLUSION: Cyst fluid from cystic VS harbored high levels of osteopontin and MCP-1, which are cytokines important in monocyte recruitment and macrophage polarization. MCP-1 may have a significant role in molding the tumor microenvironment, by polarizing monocytes to CD80 + M1 macrophages in cystic VS. Further investigations into the role of cytokines and macrophages in VS may lead to new avenues for therapeutic intervention.

Merlin-Deficient Schwann Cells Are More Susceptible to Radiation Injury than Normal Schwann Cells In Vitro.

Objectives Vestibular schwannomas (VS) are intracranial tumors, which are caused by NF2 gene mutations that lead to loss of merlin protein. A treatment for VS is stereotactic radiosurgery, a form of radiation. To better understand the radiobiology of VS and radiation toxicity to adjacent structures, our main objectives were (1) investigate effects of single fraction (SF) radiation on viability, cytotoxicity, and apoptosis in normal Schwann cells (SCs) and merlin-deficient Schwann cells (MD-SCs) in vitro, and (2) analyze expression of double strand DNA breaks (γ-H2AX) and DNA repair protein Rad51 following irradiation. Study Design This is a basic science study. Setting This study is conducted in a research laboratory. Participants Patients did not participate in this study. Main Outcome Measures In irradiated normal SCs and MD-SCs (0-18 Gy), we measured (1) viability, cytotoxicity, and apoptosis using cell-based assays, and (2) percentage of cells with γ-H2AX and Rad51 on immunofluorescence. Results A high percentage of irradiated MD-SCs expressed γ-H2AX, which may explain the dose-dependent losses in viability in rodent and human cell lines. In comparison, the viabilities of normal SCs were only compromised at higher doses of radiation (>12 Gy, human SCs), which may be related to less Rad51 repair. There were no further reductions in viability in human MD-SCs beyond 9 Gy, suggesting that <9 Gy may be insufficient to initiate maximal tumor control. Conclusion The MD-SCs are more susceptible to radiation than normal SCs, in part through differential expression of γ-H2AX and Rad51. Understanding the radiobiology of MD-SCs and normal SCs is important for optimizing radiation protocols to maximize tumor control while limiting radiation toxicity in VS patients.

Effect of Drain Output on the Timing of Closed Suction Drain (CSD) Removal After Head and Neck Surgery.

BACKGROUND: A closed suction drain (CSD) is often utilized in head and neck surgical procedures to obliterate dead space. CSDs reduce seroma and hematoma formation, thereby improving skin apposition and wound healing. The use of drains for prolonged periods of time, however, may increase the risk of wound infection. Interestingly, the evidence regarding the need for, and management of, post-operative CSDs after head and neck surgery is scarce. The current criterion of drain removal when output is less than 30 cubic centimeters (cm3) within a 24-hour period and/or on the third post-operative day (POD) is widely utilized. The aforementioned criterion is based on anecdotal evidence from small studies with specific surgical procedures. In this study, we aim to evaluate the criteria for drain removal and to lay the groundwork for an updated paradigm for drain management in head and neck oncologic surgery. STUDY DESIGN: Retrospective cohort study Setting: Academic tertiary care hospital Methods: A retrospective study was performed. Patients were included if they underwent head and neck surgery at the University of Miami Hospital between January 1, 2019 and July 1, 2020 and had at least one CSD. Volume of drain output on each POD was recorded until the day of drain removal. The development of post-operative wound complications (i.e., seroma, hematoma, infection/abscess, and dehiscence) was also recorded. RESULTS: From our initial cohort of 302 patients, 145 patients met inclusion criteria. A total of 10 patients developed a post-operative wound complication. Patients had a mean age of 58.3 ± 15.0 years. The median inter-quartile range (IQR) drain output (cm3) on the day of CSD removal from patients who developed a wound complication was similar (15; IQR, 5-37.5) when compared to those who did not develop a wound complication (25; IQR, 10-30). This difference was not statistically significant (p = 0.60). Additionally, the cohort who developed a post-operative wound complication had their drain removed on an earlier POD (1; IQR, 1-1 (Mean 1.2)) when compared to the cohort who did not develop any complications (1; IQR, 1-1 (Mean 1.5)). This difference was also not statistically significant (p = 0.48) . CONCLUSION: There is no association between drain output (cm3) or day of CSD removal with the development of wound complications. These results warrant further studies to prospectively evaluate earlier CSD removal in head and neck surgery.

Comparison of Speech Test Outcomes After Cochlear Implantation in Patients With and Without Asymmetric Hearing Loss.

OBJECTIVES: Determine whether asymmetric hearing loss (AHL) affects postoperative speech outcomes in cochlear implant (CI) patients. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital. PATIENTS: Adult English-speaking patients with unilateral CIs implanted between 2014 and 2018 were stratified into NonAHL and AHL groups based on preoperative AzBio scores in quiet from the nonimplanted ear (0-50% vs. 51-100%, respectively). INTERVENTIONS: CI surgery in the poorer performing ear. MAIN OUTCOME MEASURES: Postoperative consonant-nucleusconsonant (CNC) word and AzBio sentence test scores in quiet and/or noise at +5 dB signal-to-noise ratio (SNR). RESULTS: Of 512 patients, 33 non-AHL and 27 AHL patients were included. Average ages were 65.6 and 63.6 years, respectively. As expected, preoperative AzBio scores in quiet from the nonimplanted ear were higher in the AHL group (95% confidence interval [95%CI]: 66.4-76.4%) than the non-AHL group at baseline (95%CI: 12.3-23.6%). In both cohorts, AzBio scores in quiet from the implanted ear improved from baseline, with 24-month scores (95%CI: 73.8 - 84.9%) being higher than preoperative scores (95%CI: 13.2-23.1%). There were also significant differences in AzBio scores in quiet between cohorts overall (p  = 0.0120) on mixed model analysis, with the AHL group performing ∼6.4% better than the non-AHL group; however, differences were not significant when scores were stratified by time. In addition, there were no significant differences in CNC in quiet and AzBio scores in noise at +5 dB SNR between cohorts (p  = 0.1786 and p  = 0.6215, respectively). CONCLUSIONS: After CI, patients with AHL can achieve scores on word and sentence tests at least comparable to traditional CI candidates, supporting the expansion of CI candidacy to include patients with AHL.

N95 vs Half-face Respirator Wear in Surgical Trainees: Physiologic and Psychological Effects of Prolonged Use.

OBJECTIVES: As specialists of the upper airway, otolaryngologists are at high risk for COVID-19 transmission. N95 and half-face respirator (HFR) masks are commonly worn, each with advantages in functionality and comfort. In this study, physiologic and psychological parameters of prolonged N95 vs HFR wear were compared. STUDY DESIGN: Prospective crossover cohort study. SETTING: Single academic tertiary care hospital. METHODS: A prospective crossover cohort study was performed. Healthy otolaryngology trainees and medical students (N = 23) participated and wore N95 and HFR masks continuously for 3 hours each on separate days. Various measures were analyzed: vitals, spirometry variables, scores on the State-Trait Anxiety Inventory and HIT-6 (Headache Impact Test-6), distress, and "difficulty being understood." RESULTS: The average age was 26.3 years (SD, 3.42). There were no significant differences in vital signs and spirometry variables between N95 and HFR wear. N95 wear was associated with decreases in oxygen saturation of approximately 1.09% more than with HFRs (95% CI, 0.105-2.077). State-Trait Anxiety Inventory scores increased more with HFR wear when compared with mean changes with N95 wear (95% CI, 1.350-8.741). There were no significant differences in HIT-6 scores or distress levels between masks. The proportions of participants reporting difficulty being understood was significantly higher with HFRs. CONCLUSIONS: Oxygen saturation decreases with prolonged N95 wear, but anxiety and difficulty being understood are greater with HFR wear. Although HFRs have less resistance to gas exchange, N95 respirators may produce less anxiety and distress in clinical situations. Further studies are warranted to evaluate the clinical significance of these differences. LEVEL OF EVIDENCE: 2.

Tumor-Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing.

OBJECTIVE: (1) Characterize the distribution of M1 and M2 macrophages in vestibular schwannomas by hearing status. (2) Develop assays to assess monocyte migration and macrophage polarization in cocultures with vestibular schwannoma cells. STUDY DESIGN: Basic and translational science. SETTING: Tertiary care center. METHODS: A retrospective chart review of 30 patients with vestibular schwannoma (VS) was performed. Patients were stratified into serviceable and unserviceable hearing groups. Immunohistochemistry for CD80+ M1 and CD163+ M2 macrophages was conducted. Primary VS cultures (n = 4) were developed and cocultured with monocytes. Immunohistochemistry for macrophage markers was performed to assess monocyte migration and macrophage polarization. RESULTS: Although tumors associated with unserviceable hearing had higher levels of CD80 and CD163 than those with serviceable hearing, the relationship was only significant with CD163 (P = .0161). However, CD163 level did not remain a significant predictor variable associated with unserviceable hearing on multivariate analysis when adjusted for other variables. In vitro assays show that VS cells induced monocyte migration and polarization toward CD80+ M1 or CD163+ M2 macrophage phenotypes, with qualitative differences in CD163+ macrophage morphologies between serviceable and unserviceable hearing groups. CONCLUSION: Vestibular schwannomas express varying degrees of CD80+ M1 and CD163+ M2 macrophages. We present evidence that higher expression of CD163+ may contribute to poorer hearing outcomes in patients with VS. We also describe in vitro assays in a proof-of-concept investigation that VS cells can initiate monocyte migration and macrophage polarization. Future investigations are warranted to explore the relationships between tumor, macrophages, secreted cytokines, and hearing outcomes in patients with VS.

Fluorescent Detection of Vestibular Schwannoma Using Intravenous Sodium Fluorescein In Vivo.

BACKGROUND: Vestibular schwannoma (VS) are intracranial tumors caused by merlin deficiency. Sodium fluorescein (SF) is a fluorescent compound that accumulates in various intracranial tumors, causing tumors to emit green fluorescence after blue light excitation. HYPOTHESIS: Intravenous SF preferentially deposits in VS, helping surgeons differentiate tumor from surrounding tissue. METHODS: Merlin-deficient Schwann cells were grafted onto cochleovestibular nerves of immunodeficient rats. Rats were randomized to receive SF (7.5 mg/kg; n = 5) or saline (n = 3). Tissues were harvested at 1 hour and photographed in white and blue light. Sixteen surgeons identified and marked the tumor-tissue interfaces on images. Fluorescence was measured on tissue specimens using the IVIS imaging system and on tissue cross-sections obtained with confocal microscopy. Western blot was performed to measure levels of organic anion transporting polypeptide (OATP), a drug transporter specific for SF. RESULTS: Under blue light, tumors from SF rats demonstrated bright green fluorescence under direct visualization, higher fluorescence measurements on tissue specimens (p < 0.001), and more SF deposition on tissue cross-sections (p < 0.001), when compared with surrounding tissues and placebo rats. Surgeons were better able to distinguish the tumor-tissue interfaces in SF rats. Furthermore, the expression level of OATP1C1 was significantly higher in tumors than in surrounding tissues (p < 0.0001). CONCLUSION: In a xenograft model of VS, intravenous SF preferentially deposits in tumors, compared with normal surrounding tissue. Under blue light, tumors emit an intense green fluorescence that can help surgeons differentiate tumor from critical structures nearby, which may improve clinical outcomes in complicated VS surgery.

Effect of age, electrode array, and time on cochlear implant impedances.

Objectives: To determine the impact of age, electrode array, and time on impedance patterns in cochlear implant (CI) patients. Methods: A retrospective case review was performed on 98 patients implanted with the CI24RE perimodiolar (PM) and CI422 lateral wall (LW) arrays between 2010 and 2014 to assess impedances at the 1 week and 3-6 month visit after initial stimulation (IS). Results: With respect to age, impedances were higher in young patients compared to older patients in the middle and apical turns. With time, there were significant reductions in impedances across most electrodes. Electrode array type also had a significant impact on impedance measurements with PM and LW arrays having higher impedances in the basal turn and apical turns, respectively. Furthermore, PM arrays demonstrated significantly lower impedances in the middle and apical turn with time, when compared to LW arrays. Conclusions: Age, electrode array, and time can independently affect CI impedances. Moreover, we show that PM arrays may be advantageous to LW arrays, due to demonstrated lower impedances in the middle and apical turns long term. Understanding the impact of impedance on speech discrimination and determining the intracochlear processes that contribute to differences in impedance are future research directions.

Gene therapy for neurological disorders: challenges and recent advancements.

Major advancements in targeted gene therapy have opened up avenues for the treatment of major neurological disorders through a range of versatile modalities varying from expression of exogenous to suppression of endogenous genes. Recent technological innovations for improved gene sequence delivery have focussed on highly specific viral vector designs, plasmid transfection, nanoparticles, polymer-mediated gene delivery, engineered microRNA and in vivo clustered regulatory interspaced short palindromic repeats (CRISPR)-based therapeutics. These advanced techniques have profound applications in treating highly prevalent neurological diseases and neurodevelopmental disorders including Parkinson's disease, Alzheimer's disease and autism spectrum disorder, as well as rarer diseases such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy, lysosomal storage diseases, X-linked adrenoleukodystrophy and oncological diseases. In this article, we present an overview of the latest advances in targeted gene delivery and discuss the challenges and future direction of gene therapy in the treatment of neurological disorders.

Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Cochlear Function in an Experimental Rat Model.

Mesenchymal stem cell (MSC) therapy is an emerging treatment modality for various human diseases. Although induced pluripotent stem cells have been explored for the restoration of hearing, the potential of MSCs as a therapeutic strategy for various cochlear insults is not precisely known. MSCs possess anti-inflammatory, anti-apoptotic and neuroprotective properties, making them an attractive target for the treatment of inner ear disorders such as hair cell damage in response to inflammation. Most of the previous studies have used immunosuppression or the complex surgical techniques to deliver stem cells into the cochlea. However, no information is available regarding the biocompatibility and safety of MSCs in the inner ear in immunocompetent cochlea. The aim of the present study was to determine the effect of non-surgical administration of rodent bone marrow derived MSCs (BM-MSCs) through transtympanic delivery on the cochlear function and to assess any adverse effects on the auditory system employing a rat model without immunosuppression. We observed that the transtympanic administration of BM-MSCs has no significant effect on the hearing thresholds as determined by auditory brainstem response and distortion product otoacoustic emissions. Histopathological examination revealed no recruitment of inflammatory leukocytes and edema in the cochlea of BM-MSCs administrated rats. The results of this study suggest that transtympanic administration of BM-MSCs is safe and can be explored in providing otoprotection against cochlear insults. Anat Rec, 303:487-493, 2020. © 2019 American Association for Anatomy.

Nanoparticle-based drug delivery in the inner ear: current challenges, limitations and opportunities.

Hearing loss is the most common neurosensory impairment worldwide. While conductive hearing loss can be managed by surgery, the management of sensorineural hearing loss (SNHL), related to the damage of sensory cells of the inner ear is more challenging to manage medically. Many causes of SNHL such as sudden idiopathic SNHL, Meniere's disease, noise-induced hearing loss, autoimmune hearing loss or hearing loss from exposure to ototoxic substances can benefit from delivery of otoprotective drugs to the inner ear. However, systemic drug delivery through oral, intravenous and intramuscular methods leads to undesirable side effects due to the inner ear's limited blood supply and the relatively poor penetration of the blood-inner ear barrier (BLB). Therefore, there has been an increased interest for the targeted drug delivery to the inner ear using nanoparticles. Drug delivery through nanoparticles offers several advantages including drug stabilization for controlled release and surface modification for specific targeting. Understanding the biocompatibility of nanoparticles with cochlea and developing novel non-invasive delivery methods will promote the translation of nanoparticle-mediated drug delivery for auditory disorders from bench to bedside.