Predicting Therapeutic Response to Hypoglossal Nerve Stimulation Using Deep Learning.

OBJECTIVES: To develop and validate machine learning (ML) and deep learning (DL) models using drug-induced sleep endoscopy (DISE) images to predict the therapeutic efficacy of hypoglossal nerve stimulator (HGNS) implantation. METHODS: Patients who underwent DISE and subsequent HGNS implantation at a tertiary care referral center were included. Six DL models and five ML algorithms were trained on images from the base of tongue (BOT) and velopharynx (VP) from patients classified as responders or non-responders as defined by Sher's criteria (50% reduction in apnea-hypopnea index (AHI) and AHI < 15 events/h). Precision, recall, F1 score, and overall accuracy were evaluated as measures of performance. RESULTS: In total, 25,040 images from 127 patients were included, of which 16,515 (69.3%) were from responders and 8,262 (30.7%) from non-responders. Models trained on the VP dataset had greater overall accuracy when compared to BOT alone and combined VP and BOT image sets, suggesting that VP images contain discriminative features for identifying therapeutic efficacy. The VCG-16 DL model had the best overall performance on the VP image set with high training accuracy (0.833), F1 score (0.78), and recall (0.883). Among ML models, the logistic regression model had the greatest accuracy (0.685) and F1 score (0.813). CONCLUSION: Deep neural networks have potential to predict HGNS therapeutic efficacy using images from DISE, facilitating better patient selection for implantation. Development of multi-institutional data and image sets will allow for development of generalizable predictive models. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Functional Oral Intake in Primary Versus Salvage Laryngectomy.

OBJECTIVE: Advanced-stage laryngeal squamous cell carcinoma is treated with primary surgery or chemoradiation. We aim to determine if there are differences in postoperative functional oral intake in primary (PL) versus salvage laryngectomees (SL). STUDY DESIGN: Retrospective cohort study. SETTING: Patients who underwent laryngectomy between 2011 and 2021. METHODS: We examined demographic, diagnostic, treatment, and swallow function data pre- and postoperatively. A follow-up survey was distributed to assess current swallow status. RESULTS: One hundred twenty-five patients were included. Preoperatively, 68.8% of patients reported dysphagia. Median functional oral intake score (FOIS) was 4.0 [interquartile range, IQR: 1.0-6.75]. The SL group had lower preop FOIS [2.0; IQR: 1.0-4.75] that did not reach significance compared to the PL group [4.5; IQR: 1.0-7.0] (P = .052). 73.4% of patients had a feeding tube. The PL group was more likely to have the tube removed [odds ratio, OR: 2.4; confidence interval, CI: 1.0-5.7]. The SL group was more likely to require feeding tube placement more than 6 months postop [OR: 6.9; CI: 1.65-32.6]. SL FOIS scores improved by 3 months postop to 5 (SL ΔFOIS = 3, P = .0150). PL scores improved to 7 [PL ΔFOIS = 2, P = .0005] at 12 to 15 months. Sixty-nine patients were contacted for a follow-up survey and 16 completed this survey. 30.4% patients reported dietary restrictions (mean 4.4 years postop). CONCLUSION: Patients undergoing SL appear to obtain similar swallow outcomes compared to PL at 3 to 6 months postlaryngectomy, but plateau. The PL group continues to improve up to 1 year postoperatively. Fifty percent of patients report on-going dysphagia after 5 years.

Protection from cisplatin-induced hearing loss with lentiviral vector-mediated ectopic expression of the anti-apoptotic protein BCL-XL.

Cisplatin is a highly effective chemotherapeutic agent, but it can cause sensorineural hearing loss (SNHL) in patients. Cisplatin-induced ototoxicity is closely related to the accumulation of reactive oxygen species (ROS) and subsequent death of hair cells (HCs) and spiral ganglion neurons (SGNs). Despite various strategies to combat ototoxicity, only one therapeutic agent has thus far been clinically approved. Therefore, we have developed a gene therapy concept to protect cochlear cells from cisplatin-induced toxicity. Self-inactivating lentiviral (LV) vectors were used to ectopically express various antioxidant enzymes or anti-apoptotic proteins to enhance the cellular ROS scavenging or prevent apoptosis in affected cell types. In direct comparison, anti-apoptotic proteins mediated a stronger reduction in cytotoxicity than antioxidant enzymes. Importantly, overexpression of the most promising candidate, Bcl-xl, achieved an up to 2.5-fold reduction in cisplatin-induced cytotoxicity in HEI-OC1 cells, phoenix auditory neurons, and primary SGN cultures. BCL-XL protected against cisplatin-mediated tissue destruction in cochlear explants. Strikingly, in vivo application of the LV BCL-XL vector improved hearing and increased HC survival in cisplatin-treated mice. In conclusion, we have established a preclinical gene therapy approach to protect mice from cisplatin-induced ototoxicity that has the potential to be translated to clinical use in cancer patients.

Six-week postoperative opioid use and pain following a randomized controlled trial evaluating multimodal analgesia for head and neck free flap patients.

Introduction: Head and neck malignancy treatment often involves invasive surgeries, necessitating effective postoperative pain control. However, chronic reliance on opioid medications remains a challenge for many patients after surgery. Multimodal analgesia (MMA) within enhanced recovery after surgery protocols has shown success in limiting narcotic pain medications for other cancer types. In a prior study, MMA comprising acetaminophen, ketorolac, gabapentin, and a neurogenic block reduced opioid use in the 7-day postoperative period for major head and neck reconstructive surgery. This study investigates the impact of multimodal analgesia on opioid prescription and pain during the 6-week postoperative period for patients undergoing major head and neck oncologic surgeries, aiming to understand the longer-term effects of narcotic use. Methods: The study retrospectively examined participants in a [hybrid type 1 effectiveness-implementation pragmatic trial to assess multimodal analgesia's long-term effectiveness in head and neck free flap surgery. Arm A received scheduled acetaminophen and as-needed opioids, while Arm B received scheduled gabapentin, ketorolac, a regional nerve block at the donor site, scheduled acetaminophen, and as-needed opioids. Retrospective data collection included opioid prescription use and pain scores up to 6 weeks after surgery, gathered from the Kansas prescription drug monitoring program, K-TRACS. Results: Thirty patients participated, 14 in Arm A and 16 in Arm B. The average morphine milligram equivalents per day of filled prescriptions were not significantly different between Arm A and Arm B (7.23 vs. 7.88, p = .845). Additionally, average pain scores at 6 weeks showed no significant difference between the two groups (1.4 vs. 1.9, p = .612). Conclusion: Patients with head and neck cancer treated with multimodal analgesia during the perioperative period did not exhibit significant differences in opioid use and pain within 6 weeks after discharge. To confirm these findings, a re-examination with strict measures of opioid use and scheduled pain assessments in a prospective manner is warranted. Level of Evidence: 4.

Development and Validation of The Activity-Based Checks (ABCs) of Pain: A Functional Pain Scale.

The Activity-Based-Checks of Pain (ABCs) is a pain assessment tool incorporating activities of daily living and instrumental activities of daily living. Unlike widely used pain scales which are oftentimes unidimensional and highly subjective, the ABCs was designed to focus on function capabilities and limitations of patients due to pain. This study sought out to validate the factorial structure of the ABCs and assess its use in participants with chronic pain. Participants were recruited in two phases from Prolific - an online service designed to identify research participant recruitment based on study criteria. Phase one optimized the design of the ABCs, with 297 subjects selecting their preferred icon for each function and rating its understandability. The most preferred and understandable icons were then used in phase two, where 304 chronic pain participants completed the ABCs, PROMIS-29, additional PROMIS items that were analogous to the ABCs functions but not represented in the PROMIS-29, and the Brief Pain Inventory (BPI). Data was analyzed using exploratory factor analysis and confirmatory factor analysis demonstrating four factor loadings: multi-planal activities, sitting/hip flexor pain, walking/ambulation, and pain interference with lightweight unilateral activities. High internal consistency was demonstrated with all four factor loadings. Correlations between items in the ABCs, PROMIS, and BPI resulted in moderate to strong correlations demonstrating strong evidence for the validity of the ABCs as a functional pain assessment tool.

Right Versus Left Cuff Position for Upper Airway Stimulation.

OBJECTIVE: Upper airway stimulation (UAS) is a treatment option for obstructive sleep apnea in which electrical stimulation is applied to the hypoglossal nerve. Nerve branches that control tongue protrusion are located inferiorly. Due to positioning, left-sided implants are typically placed with an inferiorly oriented electrode cuff (L-down) as opposed to superiorly on the right (R-up). In this study, we assess the impact of left- versus right-sided UAS on patient outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary Academic Medical Center. METHODS: Patients who underwent UAS implantation between 2016 and 2021 with an L-down or R-up oriented cuff as confirmed by X-ray were included. Data were collected retrospectively. Most recent sleep study variables were used for analysis. RESULTS: A total of 190 patients met the inclusion criteria. The average age was 61.0 ± 11.0 years, with 55 (28.9%) females. L-down orientation was present in 21 (11.1%) patients vs 169 (88.9%) R-up. Indications for L-down included hunting/shooting (n = 15), prior radiation/surgery (n = 4), central port (n = 1), and brachial plexus injury (n = 1). Adherence was higher among L-down patients (47.1 vs 41.0 hours use/week, P = .037) in univariate analysis, with a similar time to adherence data collection (4.4 vs 4.2 months, P = .612), though this finding was not maintained in the multivariate regression analysis. Decrease in apnea-hypopnea index (21.3 vs 22.8, P = .734), treatment success (76.5% vs 84.0%, P = .665), functional threshold (1.5 vs 1.6, P = .550), therapeutic amplitude (2.3 vs 2.4, P = .882), and decrease in Epworth Sleepiness Scale (4.9 vs 2.6, P = .060) were not significantly different between cohorts. CONCLUSION: This study is the first to examine the orientation of the UAS electrode cuff concerning the electrodes' natural position and the potential effect on postoperative outcomes. Our study found no significantly different treatment outcomes between the L-down versus R-up cohort, with the exception of device adherence, which was significantly higher in the L-down group on univariate analysis though not on multivariate analysis. Future studies with larger patient cohorts are needed to further investigate this potential relationship between treatment outcomes and electrode cuff orientation.

Third-generation lentiviral gene therapy rescues function in a mouse model of Usher 1B.

Usher syndrome 1B (USH1B) is a devastating genetic disorder with congenital deafness, loss of balance, and blindness caused by mutations in the myosin-VIIa (MYO7A) gene, for which there is currently no cure. We developed a gene therapy approach addressing the vestibulo-cochlear deficits of USH1B using a third-generation, high-capacity lentiviral vector system capable of delivering the large 6,645-bp MYO7A cDNA. Lentivirally delivered MYO7A and co-encoded dTomato were successfully expressed in the cochlear cell line HEI-OC1. In normal-hearing mice, both cochlea and the vestibular organ were efficiently transduced, and ectopic MYO7A overexpression did not show any adverse effects. In Shaker-1 mice, an USH1B disease model based on Myo7a mutation, cochlear and vestibular hair cells, the main inner ear cell types affected in USH1B, were successfully transduced. In homozygous mutant mice, delivery of MYO7A at postnatal day 16 resulted in a trend for partial recovery of auditory function and in strongly reduced balance deficits. Heterozygous mutant mice were found to develop severe hearing loss at 6 months of age without balance deficits, and lentiviral MYO7A gene therapy completely rescued hearing to wild-type hearing thresholds. In summary, this study demonstrates improved hearing and balance function through lentiviral gene therapy in the inner ear.

Disentangling Social Determinants of Health and Rurality in Head and Neck Cancer 2-Year Mortality.

Social determinants of health (SDoH) and rurality are known factors that may influence outcomes in head and neck squamous cell carcinoma (HNSCC). Patients residing in remote locations or those with multiple SDoH may encounter barriers to initial diagnosis, adherence to multidisciplinary treatments, and posttreatment surveillance, which may impact their overall survival. However, previous studies have shown mixed results associated with rural residence. The aim of this study is to identify the impact of rurality and SDoH on 2-year survival in HNSCC. The study was conducted using a Head and Neck Cancer Registry at a single institution from June 2018 through July 2022. Rurality, defined by US census scores, and individual measures of SDoH were used. Our results indicate that each additional adverse SDoH factor results in 1.5 times the odds of mortality at 2 years. Individualized measures of SDoH, rather than rurality alone, better reflect patient prognosis in HNSCC.

Gender, Smoking History, and Age Prediction from Laryngeal Images.

Flexible laryngoscopy is commonly performed by otolaryngologists to detect laryngeal diseases and to recognize potentially malignant lesions. Recently, researchers have introduced machine learning techniques to facilitate automated diagnosis using laryngeal images and achieved promising results. The diagnostic performance can be improved when patients' demographic information is incorporated into models. However, the manual entry of patient data is time-consuming for clinicians. In this study, we made the first endeavor to employ deep learning models to predict patient demographic information to improve the detector model's performance. The overall accuracy for gender, smoking history, and age was 85.5%, 65.2%, and 75.9%, respectively. We also created a new laryngoscopic image set for the machine learning study and benchmarked the performance of eight classical deep learning models based on CNNs and Transformers. The results can be integrated into current learning models to improve their performance by incorporating the patient's demographic information.

Quantifying Faculty Perception of Diversity, Equity, and Inclusion Within Academic Otolaryngology-Head and Neck Surgery Departments.

OBJECTIVE: Investigating faculty perceptions of diversity, equity, and inclusion (DEI) among academic otolaryngology programs. STUDY DESIGN: Quantitative survey. SETTING: Academic otolaryngology departments. METHODS: The DEI Inventory was developed by a multi-institutional health equity consortium and disseminated within 16 academic otolaryngology programs. The inventory consisted of 25 items graded on a 5-point Likert scale (strongly disagree to strongly agree), 2 yes/no questions, and 5 items reflecting overall DEI, stress, and burnout among academic otolaryngologists. Validated imposter phenomenon and personality trait measures were also included. RESULTS: The inventory received 158 (31.0%) partial and 111 (21.8%) full responses. No significant differences were identified in DEI scores by race. Compared to males, females reported lower scores on the overall DEI Inventory (3.6 vs 4.3, p < .001). Female respondents also reported greater levels of imposter phenomenon than their male counterparts (53.2 vs 47.5, p = .049). CONCLUSION: Preliminary responses to our DEI Inventory suggest that faculty perception of DEI is not impacted by race. Female faculty report considerably lower perceptions of DEI than their male counterparts and experience greater levels of imposter phenomenon. The results of the DEI Inventory can help departments design meaningful interventions to improve levels of DEI among faculty.

Association of Social-Ecological Factors With Delay in Time to Initiation of Postoperative Radiation Therapy: A Prospective Cohort Study.

Importance: Timely initiation of postoperative radiation therapy (PORT) is associated with reduced recurrence rates and improved overall survival in patients with head and neck squamous cell carcinoma (HNSCC). Measurement of the association of social-ecological variables with PORT delays is lacking. Objective: To assess individual and community-level factors associated with PORT delay among patients with HNSCC. Design, Setting, and Participants: This prospective cohort study carried out between September 2018 and June 2022 included adults with untreated HNSCC who were enrolled in a prospective registry at a single academic tertiary medical center. Demographic information and validated self-reported measures of health literacy were obtained at baseline visits. Clinical data were recorded, and participant addresses were used to calculate the area deprivation index (ADI), a measure of community-level social vulnerability. Participants receiving primary surgery and PORT were analyzed. Univariable and multivariable regression analysis was performed to identify risk factors for PORT delays. Exposures: Surgical treatment and PORT. Main Outcomes and Measures: The primary outcome was PORT initiation delay (>42 days from surgery). Risk of PORT initiation delay was evaluated using individual-level (demographic, health literacy, and clinical data) and community-level information (ADI and rural-urban continuum codes). Results: Of 171 patients, 104 patients (60.8%) had PORT delays. Mean (SD) age of participants was 61.0 (11.2) years, 161 were White (94.2%), and 105 were men (61.4%). Insurance was employer-based or public among 65 (38.5%) and 75 (44.4%) participants, respectively. Mean (SD) ADI (national percentile) was 60.2 (24.4), and 71 (41.8%) resided in rural communities. Tumor sites were most commonly oral cavity (123 [71.9%]), with 108 (63.5%) classified as stage 4 at presentation. On multivariable analysis, a model incorporating individual-level factors with health literacy in addition to community-level factors was most predictive of PORT delay (AOC= 0.78; R2, 0.18). Conclusions and Relevance: This cohort study provides a more comprehensive assessment of predictors of PORT delays that include health literacy and community-level measures. Predictive models that incorporate multilevel measures outperform models with individual-level factors alone and may guide precise interventions to decrease PORT delay for at-risk patients with HNSCC.

Assessing the Risk of Adjuvant Radiotherapy Initiation Delays With Social Support Surveys.

OBJECTIVE: In patients with head and neck squamous cell carcinoma (HNSCC), initiating postoperative radiotherapy (PORT) greater than 42 days after surgery is associated with a higher risk of poor survival outcomes. Social support has been shown to modulate behaviors related to care-seeking and treatment adherence. In this study, we sought to determine the relationship between social support metrics and PORT delays. STUDY DESIGN: Prospective cohort study. SETTING: Single tertiary medical center. METHODS: Patients with HNSCC who underwent primary surgical excision requiring PORT were prospectively enrolled. Patient-perceived social support metrics were assessed using the Medical Outcomes Study Social Support Survey (MOS-SSS) at initial presurgical evaluation. Associations with PORT delays were evaluated via univariable and multivariable logistic regression analysis. RESULTS: A total of 111 patients met the inclusion criteria for the study. An additional 28 patients were recommended to receive PORT but did not initiate treatment and were included for secondary analysis. All four subscales of the MOS-SSS (positive social interaction, affectionate support, tangible support, and emotional/informational support) were significantly associated with PORT initiation delays on univariable analysis. On multivariable analysis, the overall MOS-SSS score (odds ratio [OR] 2.08, 1.15-4.35, p = .028) was significantly associated with PORT initiation delays. On secondary analysis, lower tangible support was associated with a lack of PORT initiation (OR 1.63, 1.05-2.54, p = .028). CONCLUSION: Social support metrics were significantly associated with PORT delays, which may help promote tighter scheduling and closer monitoring of high-risk patients.

Long-term trends in body mass index throughout upper airway stimulation treatment: does body mass index matter?

STUDY OBJECTIVES: Upper airway stimulation is a surgical option for patients with obstructive sleep apnea who fail other forms of noninvasive treatment. Current guidelines recommend a baseline body mass index (BMI) below 32 kg/m2 for eligibility. In this study, we identify trends in BMI before and after upper airway stimulation to characterize the influence of BMI on treatment success. METHODS: Patients underwent upper airway stimulation implantation between 2016 and 2021. Sleep study data were collected from preoperative and most recent postoperative sleep study. BMI data were collected and compared across the following time points: preoperative sleep study (BMI-1), initial surgeon consultation (BMI-2), surgery (BMI-3), titration polysomnogram (BMI-4), and second postoperative sleep study (BMI-5). Patients were categorized into groups (BMI ≥32 [BMI32], 25 ≤ BMI <32 [BMI25], BMI <25 [BMI18]) based BMI-1, and clinical outcomes were compared. RESULTS: 253 patients were included. The BMI32 group showed a significant decrease in BMI between BMI-1 and BMI-3 (33.9 vs 32.2; P < .001) and a significant increase in BMI between BMI-3 and BMI-5 (32.2 vs 33.0; P = .047). Apnea-hypopnea index improvement and treatment success rate were not significantly different between groups. On univariate and multivariable logistic regression, a lower BMI-5 was significantly predictive of treatment success (odds ratio: 0.88; 95% confidence interval: 0.79-0.97; P = .016). BMI-5 was also significantly associated with improvement in apnea-hypopnea index (P = .002). Other BMI time points were not associated with measures of treatment success. CONCLUSIONS: Reduced BMI after upper airway stimulation implantation, as opposed to baseline BMI, predicted treatment success. These findings may guide patient counseling, with implications for long-term adherence and therapy success. CITATION: Renslo B, Virgen CG, Sawaf T, et al. Long-term trends in body mass index throughout upper airway stimulation treatment: does body mass index matter? J Clin Sleep Med. 2023;19(6):1061-1071.

Team Consistency in Reducing Operative Time in Head and Neck Surgery with Microvascular Free Flap Reconstruction.

OBJECTIVE(S): To evaluate the impact of consistent surgical teams on procedure duration in head and neck free tissue transfer, and to evaluate the length of stay and readmission rates with consistent teams. METHODS: A retrospective chart review of head and neck microvascular reconstruction by a single surgeon between August 2017 and November 2021 was performed. Procedure duration, wound complications, length of stay, and 30-day readmissions were analyzed. One circulating nurse (CN) and surgical technologist (ST) were considered "consistent" due to their prior work with the primary surgeon. All others were considered "ad hoc." Teams were "Consistent CN + ST," "Consistent ST," "Consistent CN," or "Ad hoc." Procedure duration between groups was compared via analysis of variance. Multivariate linear regression was performed to predict procedure duration. RESULTS: A total of 135 patients were included. Age, sex, and American Society of Anesthesiologists status did not significantly differ across groups (p = 0.963; p = 0.467; p = 0.908, respectively). The mean procedure duration was 339.3 min and differed significantly across all groups (p = 0.006, Cohen d = 0.32). Compared to the Ad hoc group, consistent teams demonstrated significant reductions in mean procedure duration (Consistent CN + ST: 58.4 min, p = 0.001, Cohen d = 0.67; Consistent ST: 51.6 min, p = 0.013, Cohen d = 0.61; Consistent CN: 44.5 min, p = 0.031, Cohen d = 0.52). Controlling for other factors, the ad hoc team predicted increased procedure duration on multivariate analysis ( ß 57.38, 19.92-94.85, p < 0.003). Wound complications, length of stay, and readmission rates did not differ significantly across groups (p = 0.940; p = 0.174; p = 0.935, respectively). CONCLUSION: Consistent CN and ST improve operative efficiency in head and neck-free tissue transfer. Future studies may evaluate the impact of team consistency on complications, physician burnout, and health systems costs. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2154-2159, 2023.

Effects of Prior Tracheostomy on Total Laryngectomy Outcomes.

OBJECTIVE: To assess whether preoperative tracheostomy (PreOT) increases risk of complications after total laryngectomy (TL) and to determine if timing of tracheostomy creation is associated with an increased risk. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital between 2007 and 2020. METHODS: Inclusion criteria were patients who underwent primary or salvage TL for oncologic treatment. Dependent variables of interest included surgical complications, such as wound dehiscence, infection, hematoma, complete flap failure, fistula formation, and stoma stenosis, as well as medical complications. Categorical variables were compared with chi-square test or Fisher exact test, and continuous variables were compared with an independent t test. Multivariable regression was conducted to assess predictors of complications after laryngectomy. RESULTS: A total of 306 patients were included. Primary TL was performed in 161 (53%) patients and salvage in 145 (47%) patients. Of the patients undergoing primary laryngectomy, 105 (65%) received a PreOT. Of the patients undergoing salvage laryngectomy, 86 (59%) received a PreOT. In both primary and salvage cases, there was no association between PreOT and surgical or medical complications. Additionally, there was no significant association between timing of tracheostomy and surgical complications. On multivariable analysis, the presence of a PreOT was not associated with surgical complications. In salvage cases, those with a PreOT had a significantly longer average length of stay than those without a PreOT (12 vs 9 days, P = .008). CONCLUSION: PreOT in patients undergoing primary and salvage laryngectomies was not associated with surgical or medical complications postlaryngectomy. Timing of tracheostomy in relation to laryngectomy was not found to adversely affect clinical outcomes.

Feasibility of collagen matrix tiles with cesium-131 brachytherapy for use in the treatment of head and neck cancer.

BACKGROUND: Locoregional failure is a unique and challenging problem in head and neck cancer with controversy surrounding the use of re-irradiation in the treatment. We aimed to evaluate the dosimetry and technical parameters in utilizing a collagen matrix with embedded Cesium-131 (Cs-131) radioactive isotope seeds as it relates to dose distribution and dose to carotid artery. METHODS AND MATERIALS: Cadaveric feasibility study randomizing Cs-131 strands alone or Cs-131 with collagen matrix to be placed into neck dissection defects. For the dose computation, physicists employed the TG-43 dosimetry calculation algorithm with a point source assumption to compute the dose. Carotid arteries were contoured in MIM-Symphony software and the carotid artery maximum and mean doses were calculated in accordance with TG-43 specifications. Ease of use of collagen matrix tiles on a 7-point Likert scale and mean radiation dose to the carotid artery. RESULTS: Ease of use score was higher in collagen matrix compared to stranded seeds with a mean score of 6.3 +/- 1.2 compared to 4.5 +/- 0.87. Time of implantation was statistically significantly, p = 0.031, lower in the collagen matrix group (M = 5.17 min, SD = 4.62) compared to stranded seeds (M = 15.83 min, SD = 3.24). Mean radiation dose to the carotid artery was 62.8 Gy +/- 9.46 in the collagen matrix group compared to 108.2 Gy +/- 55.6 in the traditional Cs-131 seeds group. CONCLUSIONS: We present a feasibility and concept cadaveric study using a collagen matrix with Cesium-131 demonstrating preliminary evidence to support its ease of use, decreased time to implantation, and decreased dose delivered to the carotid artery.

Palatal Coupling Maneuvers Do Not Predict Hypoglossal Nerve Stimulator Treatment Efficacy.

OBJECTIVE(S): Maneuvers during drug-induced sleep endoscopy (DISE), for patients with obstructive sleep apnea (OSA), have been used as predictors for success with oral appliances. Hypoglossal nerve stimulation (HGNS) promotes opening at the velum through palatoglossus coupling. In this study, we evaluate maneuvers during DISE as predictors for HGNS treatment efficacy. METHODS: We evaluated patients undergoing HGNS between November, 2014 and February, 2021. We assessed maneuvers including jaw thrust and chin lift during preoperative DISE. The impact of tongue base and palatal opening during these maneuvers were rated from 1 to 4 (1: no improvement, 2: mild improvement, 3: moderate improvement, 4: significant improvement). Patients were grouped by a score of 1-2 (weak response) or 3-4 (strong response). Apnea hypopnea index (AHI) change was calculated from the difference between preoperative and postoperative sleep study. RESULTS: One hundred and seventy one patients were included. With jaw thrust, there was no significant difference in AHI change between patients with weak or strong response at the palate (n = 68 vs. 94, 9.5 vs. 13.6, p = 0.21) or tongue base (n = 24 vs. 138, 16.6 vs. 11.3, p = 0.24). On chin lift, there was no significant difference at the palate (n = 82 vs. 18, 13.9 vs. 11.4, p = 0.63) or tongue base (n = 92 vs. 72, 10.8 vs. 14.6, p = 0.24). On multiple linear regression analysis, lower body mass index, higher preoperative AHI, and higher preoperative oxygen nadir were associated with a larger AHI change. CONCLUSION: Palatal coupling maneuvers during DISE are not predictive of AHI change with HGNS. Findings using these maneuvers should not preclude HGNS candidacy. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:431-436, 2023.

CRISPR-Cas9 Engineered Extracellular Vesicles for the Treatment of Dominant Progressive Hearing Loss.

Clinical translation of gene therapy has been challenging, due to limitations in current delivery vehicles such as traditional viral vectors. Herein, we report the use of gRNA:Cas9 ribonucleoprotein (RNP) complexes engineered extracellular vesicles (EVs) for in vivo gene therapy. By leveraging a novel high-throughput microfluidic droplet-based electroporation system (µDES), we achieved 10-fold enhancement of loading efficiency and more than 1000-fold increase in processing throughput on loading RNP complexes into EVs (RNP-EVs), compared with conventional bulk electroporation. The flow-through droplets serve as enormous bioreactors for offering millisecond pulsed, low-voltage electroporation in a continuous-flow and scalable manner, which minimizes the Joule heating influence and surface alteration to retain natural EV stability and integrity. In the Shaker-1 mouse model of dominant progressive hearing loss, we demonstrated the effective delivery of RNP-EVs into inner ear hair cells, with a clear reduction of Myo7ash1 mRNA expression compared to RNP-loaded lipid-like nanoparticles (RNP-LNPs), leading to significant hearing recovery measured by auditory brainstem responses (ABR).

Medical Cannabis Use Reduces Opioid Prescriptions in Patients With Osteoarthritis.

Background Osteoarthritis (OA) can result in significant pain, requiring pain management with opioids. Medical cannabis (MC) has the potential to be an alternative to opioids for chronic pain conditions. This study investigates whether MC used in the management of OA-related chronic pain can reduce opioid utilization. Methods Forty patients with chronic OA pain were certified for MC. Average morphine milligram equivalents (MME) per day of opioid prescriptions filled within the six months prior to MC certification was compared to that of the six months after. Visual analog scale (VAS) for pain and Global Health scores were measured at baseline, three, and six months post MC certification. Results Average MME/day decreased from 18.2 to 9.8 (n=40, p<0.05). The percentage of patients who dropped to 0 MME/day was 37.5%. VAS scores decreased significantly at three and six months, and Global Physical Health score increased significantly by three months. Conclusions MC reduces opioid prescription for patients with chronic OA pain and improves pain and quality of life.