Localized delivery of therapeutics impact laryngeal mechanics, local inflammatory response, and respiratory microbiome following upper airway intubation injury in swine.

BACKGROUND: Laryngeal injury associated with traumatic or prolonged intubation may lead to voice, swallow, and airway complications. The interplay between inflammation and microbial population shifts induced by intubation may relate to clinical outcomes. The objective of this study was to investigate laryngeal mechanics, tissue inflammatory response, and local microbiome changes with laryngotracheal injury and localized delivery of therapeutics via drug-eluting endotracheal tube. METHODS: A simulated traumatic intubation injury was created in Yorkshire crossbreed swine under direct laryngoscopy. Endotracheal tubes electrospun with roxadustat or valacyclovir- loaded polycaprolactone (PCL) fibers were placed in the injured airway for 3, 7, or 14 days (n = 3 per group/time and ETT type). Vocal fold stiffness was then evaluated with normal indentation and laryngeal tissue sections were histologically examined. Immunohistochemistry and inflammatory marker profiling were conducted to evaluate the inflammatory response associated with injury and ETT placement. Additionally, ETT biofilm formation was visualized using scanning electron microscopy and micro-computed tomography, while changes in the airway microbiome were profiled through 16S rRNA sequencing. RESULTS: Laryngeal tissue with roxadustat ETT placement had increasing localized stiffness outcomes over time and histological assessment indicated minimal epithelial ulceration and fibrosis, while inflammation remained severe across all timepoints. In contrast, vocal fold tissue with valacyclovir ETT placement showed no significant changes in stiffness over time; histological analysis presented a reduction in epithelial ulceration and inflammation scores along with increased fibrosis observed at 14 days. Immunohistochemistry revealed a decline in M1 and M2 macrophage markers over time for both ETT types. Among the cytokines, IL-8 levels differed significantly between the roxadustat and valacyclovir ETT groups, while no other cytokines showed statistically significant differences. Additionally, increased biofilm formation was observed in the coated ETTs with notable alterations in microbiota distinctive to each ETT type and across time. CONCLUSION: The injured and intubated airway resulted in increased laryngeal stiffness. Local inflammation and the type of therapeutic administered impacted the bacterial composition within the upper respiratory microbiome, which in turn mediated local tissue healing and recovery.

Characterization of the Vertical Stiffness Gradient in Cadaveric Human and Excised Canine Larynges.

The elastic properties of the folds govern the characteristics of vocal fold vibrations. This study addresses existing gaps by investigating the Young's modulus along the anterior-posterior direction in excised canine and cadaveric human vocal folds. Micro-indentation testing was conducted on six excised canines and three cadaveric human larynges. Multiple points along the medial glottal wall were indented to determine force-displacement, stress-strain relationships, and Young's modulus as a function of Green's strain. A vertical stiffness gradient was consistently observed in both canine and human samples, with higher stiffness in the inferior aspect compared with the superior aspect. The stiffness increased toward both the anterior and posterior directions from the mid-coronal plane, with a more pronounced increase at the posterior edge. Human vocal folds generally exhibited lower stiffness at low strains but were comparable to canine vocal folds at higher strains. These findings suggest that the canine larynx model is a reasonable representation of the human laryngeal tissues' elastic property trends. This analysis of the vertical stiffness gradient in canine and human vocal folds provides valuable data for improving experimental and numerical models of phonation.

Comparison of Aerodynamic and Elastic Properties in Tissue and Synthetic Models of Vocal Fold Vibrations.

Three laryngeal models were used to investigate the aerodynamic and elastic properties of vocal fold vibration: cadaveric human, excised canine, and synthetic silicone vocal folds. The aim was to compare the characteristics of these models to enhance our understanding of phonatory mechanisms. Flow and medial glottal wall geometry were acquired via particle image velocimetry. Elastic properties were assessed from force-displacement tests. Relatively, the human larynges had higher fundamental frequency values, while canine and synthetic models exhibited greater flow rates. Canine models demonstrated the highest divergence angles and vertical stiffness gradients followed by the human model, both displaying flow separation vortices during closing. Synthetic models, whose advantage is their accessibility and repeatability, displayed the lowest glottal divergence angles and total circulation values compared to tissue models with no flow separation vortices. The elasticity tests revealed that tissue models showed significant hysteresis and vertical stiffness gradients, unlike the synthetic models. These results underscore the importance of model selection based on specific research needs and highlight the potential of canine and synthetic models for controlled experimental studies in phonation.

3D-printed neck phantoms with detailed anatomy for ultrasound-guided procedure and device testing.

Objectives: With rapid advances in ultrasound-guided procedures, there is an unmet need for echogenic phantoms with sufficient anatomical details for artificial intelligence and ultrasound-guided device testing. We developed a method for creating neck phantoms for novel otolaryngology-related device testing. To achieve accurate representation of the anatomy, we utilized CT scans and 3D printing technology to create customized agar molds, thus providing high-fidelity yet cost-effective tools. Methods: Based on previous studies, the key components in our neck phantom include the cervical vertebrae, trachea, common carotid arteries, internal jugular veins, thyroid gland, and surrounding soft tissue. Open-source image analysis software were employed to process CT data to generate high fidelity 3D models of the target structures. Resin molds were 3D printed and filled with various agar mixtures to mimic anatomical echogenicity. Results: Following the method proposed, we successfully assembled the neck phantom which provided a detailed representation of the target structures. To evaluate the results, ultrasound data was collected on the phantom and living tissue and analyzed with ImageJ. We were able to demonstrate echogenicity comparable to that of living tissue. Conclusion: The proposed method for building neck phantoms with detailed anatomical features offers a valuable, detailed, low-cost tool for medical training and device testing in otolaryngology, particularly for novel devices that involve artificial intelligence (AI) guidance and robotic-based needle insertion. Additional anatomical refinements and validation studies could further enhance the consistency and accuracy, thus paving the way for future advancements in ultrasound training and research, and ultimately benefiting patient care and safety.

Tracheal Anastomosis Leaks Across Suture Techniques and Tensions: A Biomechanical Ex Vivo Study.

BACKGROUND: Anastomotic leak after tracheal resection may occur while coughing in the early postoperative period. We investigated the varying effects of suturing technique, stretch, and tension on anastomotic leaks during simulated coughs. METHODS: End-to-end anastomoses were performed using continuous or interrupted sutures on excised porcine larynges. Tracheas were secured to a pressurized system simulating cough forces, submerged in a water bath, and stretched to 1, 2, and 3 cm above baseline. Peak pressure, incomplete cough generation, and observed leakages were recorded. Parameters were analyzed using Analysis of Variance (ANOVA), multiple linear regression, and logistic regression modeling. RESULTS: Peak tension (B = -0.660, p < 0.001) and stretch lengths (B = -0.329, p = 0.006) were associated with variance in peak pressure (R2 = 0.77, F(3,294) = 8.182, p < 0.001). Incomplete coughs increased with higher peak tension (odds ratio [OR] = 15.627, p < 0.001) and stretching to 3 cm above baseline (OR = 4.335, p < 0.007). Similarly, leak occurrences, primarily from the posterior tracheal wall, increased with higher peak tension (OR = 1.787, p < 0.001) and stretching to 3 cm (OR = 2.613, p = 0.017). No significance was identified with suturing technique. CONCLUSION: Interrupted and continuous suture techniques do not differ in anastomotic strength during simulated coughs. Increased peak tracheal tension is associated with a weaker anastomosis, and tracheal stretch to 3 cm was associated with a weaker anastomosis. Our study supports the commonly held clinical belief that, to create a stronger anastomosis, tension should be minimized, and particular attention should be placed at the posterior tracheal wall during closure. LEVEL OF EVIDENCE: N/A, Benchtop study Laryngoscope, 2024.

Drug delivery systems for wound healing treatment of upper airway injury.

INTRODUCTION: Endotracheal intubation is a common procedure to maintain an open airway with risks for traumatic injury. Pathological changes resulting from intubation can cause upper airway complications, including vocal fold scarring, laryngotracheal stenosis, and granulomas and present with symptoms such as dysphonia, dysphagia, and dyspnea. Current intubation-related laryngotracheal injury treatment approaches lack standardized guidelines, relying on individual clinician experience, and surgical and medical interventions have limitations and carry risks. AREAS COVERED: The clinical and preclinical therapeutics for wound healing in the upper airway are described. This review discusses the current developments on local drug delivery systems in the upper airway utilizing particle-based delivery systems, including nanoparticles and microparticles, and bulk-based delivery systems, encompassing hydrogels and polymer-based approaches. EXPERT OPINION: Complex laryngotracheal diseases pose challenges for effective treatment, struggling due to the intricate anatomy, limited access, and recurrence. Symptomatic management often requires invasive surgical procedures or medications that are unable to achieve lasting effects. Recent advances in nanotechnology and biocompatible materials provide potential solutions, enabling precise drug delivery, personalization, and extended treatment efficacy. Combining these technologies could lead to groundbreaking treatments for upper airways diseases, significantly improving patients' quality of life. Research and innovation in this field are crucial for further advancements.

Identification of temporal shifts of oral bacteria in bone regeneration following mandibular bone defect injury and therapeutic surgery in a porcine model.

BACKGROUND: Considered the second largest and most diverse microbiome after the gut, the human oral ecosystem is complex with diverse and niche-specific microorganisms. Although evidence is growing for the importance of oral microbiome in supporting a healthy immune system and preventing local and systemic infections, the influence of craniomaxillofacial (CMF) trauma and routine reconstructive surgical treatments on community structure and function of oral resident microbes remains unknown. CMF injuries affect a large number of people, needing extensive rehabilitation with lasting morbidity and loss of human productivity. Treatment efficacy can be complicated by the overgrowth of opportunistic commensals or multidrug-resistant pathogens in the oral ecosystem due to weakened host immune function and reduced colonization resistance in a dysbiotic oral microbiome. AIMS: To understand the dynamics of microbiota's community structure during CMF injury and subsequent treatments, we induced supra-alveolar mandibular defect in Hanford miniature swine (n = 3) and compared therapeutic approaches of immediate mandibullar reconstructive (IMR) versus delayed mandibullar reconstructive (DMR) surgeries. METHODS: Using bacterial 16S ribosomal RNA gene marker sequencing, the composition and abundance of the bacterial community of the uninjured maxilla (control) and the injured left mandibula (lingual and buccal) treated by DMR were surveyed up to 70-day post-wounding. For the injured right mandibula receiving IMR treatment, the microbial composition and abundance were surveyed up to 14-day post-wounding. Moreover, we measured sera level of biochemical markers (e.g., osteocalcin) associated with bone regeneration and healing. Computed tomography was used to measure and compare mandibular bone characteristics such as trabecular thickness between sites receiving DMR and IMR therapeutic approaches until day 140, the end of study period. RESULTS: Independent of IMR versus DMR therapy, we observed similar dysbiosis and shifts of the mucosal bacteria residents after CMF injury and/or following treatment. There was an enrichment of Fusobacterium, Porphyromonadaceae, and Bacteroidales accompanied by a decline in Pasteurellaceae, Moraxella, and Neisseria relative abundance in days allotted for healing. We also observed a decline in species richness and abundance driven by reduction in temporal instability and inter-animal heterogeneity on days 0 and 56, with day 0 corresponding to injury in DMR group and day 56 corresponding to delayed treatment for DMR or injury and immediate treatment for the IMR group. Analysis of bone healing features showed comparable bone-healing profiles for IMR vs. DMR therapeutic approach.

Endotracheal tubes with dexamethasone eluting electrospun coating improve tissue mechanical function after upper airway injury.

Corticosteroid-eluting endotracheal tubes (ETTs) were developed and employed in a swine laryngotracheal injury model to maintain airway patency and provide localized drug delivery to inhibit fibrotic scarring. Polycaprolactone (PCL) fibers with or without dexamethasone were electrospun onto the ETT surface PCL-only coated ETTs and placed in native airways of 18 Yorkshire swine. Regular and dexamethasone-PCL coated ETTs were placed in airways of another 18 swine injured by inner laryngeal mucosal abrasion. All groups were evaluated after 3, 7 and 14 days (n = 3/treatment/time). Larynges were bisected and localized stiffness determined by normal indentation, then sequentially matched with histological assessment. In the native airway, tissue stiffness with PCL-only ETT placement increased significantly from 3 to 7 days (p = 0.0016) and 3 to 14 days (p < 0.0001) while dexamethasone-PCL ETT placement resulted in stiffness decreasing from 7 to 14 days (p = 0.031). In the injured airway, localized stiffness at 14 days was significantly greater after regular ETT placement (23.1 ± 0.725 N/m) versus dexamethasone-PCL ETTs (17.10 ± 0.930 N/m, p < 0.0001). Dexamethasone-loaded ETTs were found to reduce laryngotracheal tissue stiffening after simulated intubation injury compared to regular ETTs, supported by a trend of reduced collagen in the basement membrane in injured swine over time. Findings suggest localized corticosteroid delivery allows for tissue stiffness control and potential use as an approach for prevention and treatment of scarring caused by intubation injury.

A Large Cohort Analysis of Epiglottic Phenotypes and Pharyngeal Residue.

OBJECTIVE: To describe the phenotypic characteristics of the epiglottis at rest and their impact on vallecular residue. METHODS: Videofluoroscopic studies (VFSS) were pooled from 2 Laryngology practices, and Image J was used to measure epiglottic anatomic features at rest. Studies were rated by the MBSImp and presence of vallecular residue following swallow of thin and puree boluses. A conditional inference tree analysis was performed to isolate which epiglottic parameters were risk factors for presence of vallecular reside followed by logistic regression. RESULTS: The majority of patients had a normal shaped epiglottis, followed by omega shape. The mean angle of the epiglottis from the hyoid was approximately 90°. Only abnormal epiglottic movement was associated with increased risk of residue for thin boluses (OR 35.09, CI 10.93-158.66, P < .001). However, in those with normal epiglottic movement, age >70 years old was associated with increased risk of residue (OR 3.98, CI 1.73-9.23, P = .001). For puree boluses, a normal or omega shaped epiglottis was associated with residue (OR 5.19, CI 2.41-11.51, P < .001), and this relationship was further modulated by increased distance of the epiglottic tip from the posterior pharyngeal wall. No other anatomic features of the resting epiglottis were associated with residue. Comorbidities potentially affecting swallow were infrequent in the cohort and were not associated with residue. CONCLUSION: Abnormal epiglottic movement is associated with aspiration, and in this study we find that abnormal epiglottic movement increases the risk of vallecular residue and that older age is a risk factor for residue. The resting properties of the epiglottis do not appear to be associated with abnormal epiglottic movement or residue.

Changes in vocal fold gene expression and histology after injection augmentation in a recurrent laryngeal nerve injury model.

OBJECTIVE: To investigate changes in neuroregenerative pathways with vocal fold denervation in response to vocal fold augmentation. METHODS: Eighteen Yorkshire crossbreed swine underwent left recurrent laryngeal nerve transection, followed by observation or augmentation with carboxymethylcellulose or calcium hydroxyapatite at two weeks. Polymerase chain reaction expression of genes regulating muscle growth (MyoD1, MyoG and FoxO1) and atrophy (FBXO32) were analysed at 4 and 12 weeks post-injection. Thyroarytenoid neuromuscular junction density was quantified using immunohistochemistry. RESULTS: Denervated vocal folds demonstrated reduced expression of MyoD1, MyoG, FoxO1 and FBXO32, but overexpression after augmentation. Healthy vocal folds showed increased early and late MyoD1, MyoG, FoxO1 and FBXO32 expression in all animals. Neuromuscular junction density had a slower decline in augmented compared to untreated denervated vocal folds, and was significantly reduced in healthy vocal folds contralateral to augmentation. CONCLUSION: Injection augmentation may slow neuromuscular degeneration pathways in denervated vocal folds and reduce compensatory remodelling in contralateral healthy vocal folds.

Surgical Outcomes in Zenker Diverticula: A Multicenter, Prospective, Longitudinal Study.

OBJECTIVE: To compare improvement in patient-reported outcomes (PROM) in persons undergoing endoscopic and open surgical management of Zenker diverticula (ZD). METHODOLOGY: Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeus Hypertonicity (POUCH) Collaborative who underwent surgery for ZD. Patient survey, radiography reports, and the 10-item Eating Assessment Tool (EAT-10) pre- and post-procedure were abstracted from a REDCap database, which summarized means, medians, percentages, and frequencies of. Outcome based on operative intervention (endoscopic vs. open) was compared using t-test, Wilcoxon rank sum test or chi-square test, as appropriate. RESULTS: One hundred and forty-seven persons were prospectively followed. The mean age (SD) of the cohort was 68.7 (11.0). Overall, 66% of patients reported 100% improvement in EAT-10; 81% of patients had greater than 75% improvement; and 88% had greater than 50% improvement. Endoscopic was used for n = 109 patients, and open surgical intervention was used for n = 38. The median [interquartile range, IQR] EAT-10 percent improvement for endoscopic treatment was 93.3% [72, 100], and open was 100% [92.3, 100] (p = 0.05). The incidence of intraoperative complications was 3.7% for endoscopic and 7.9% for open surgical management. The median [IQR] in follow-up was 86 and 97.5 days, respectively. CONCLUSION: Both endoscopic and open surgical management of ZD provide significant improvement in patient-reported outcomes. The data suggest that open diverticulectomy may provide a modest advantage in symptomatic improvement compared to endoscopic management. The data suggest that the postoperative complication rate is higher in the open surgical group. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:97-102, 2024.

Biomechanical Evaluation of Tracheal Needle Puncture Forces: Comparative Analysis of Annular Ligaments and Tracheal Cartilage.

Percutaneous tracheotomies (PCT) are commonly performed minimally invasive procedures involving the creation of an airway opening through an incision or puncture of the tracheal wall. While the medical intervention is crucial for critical care and the management of acute respiratory failure, tracheostomy complications can lead to severe clinical symptoms due to the alterations of the airways biomechanical properties/structures. The causes and mechanisms underlaying the development of these post-tracheotomy complications remain largely unknown. In this study, we aimed to investigate the needle puncture process and its biomechanical characteristics by using a well establish porcine ex vivo trachea to simulate the forces involved in accessing airways during PCT at varying angular approaches. Given that many procedures involve inserting a needle into the trachea without direct visualization of the tracheal wall, concerns have been raised over the needle punctures through the cartilaginous rings as compared to the space between them may result in fractured cartilage and post-tracheostomy airway complications. We report a difference in puncture force between piercing the cartilage and the annular ligaments and observe that the angle of puncture does not significantly alter the puncture forces. The data collected in this study can guide the design of relevant biomechanical feedback system during airway access procedures and ultimately help refine and optimize PCT.

Effect of continuous local dexamethasone on tissue biomechanics and histology after inhalational burn in a preclinical model.

Objective: Inhalational burns frequently lead to dysphonia and airway stenosis. We hypothesize local dexamethasone delivery via a novel drug-eluting electrospun polymer-mesh endotracheal tube (ETT) reduces biomechanical and histologic changes in the vocal folds in inhalational burn. Methods: Dexamethasone-loaded polymer mesh was electrospun onto ETTs trimmed to transglottic endolaryngeal segments and secured in nine Yorkshire Crossbreed swine with directed 150°C inhalation burns. Uncoated ETTs were implanted in nine additional swine with identical burns. ETT segments were maintained for 3 and 7 days. Vocal fold (VF) structural stiffness was measured using automated-indentation mapping and compared across groups and to four uninjured controls, and matched histologic assessment performed. Statistical analysis was conducted using two-way ANOVA with Tukey's post hoc test and Wilcoxon rank-sum test. Results: VF stiffness after burn decreased with longer intubation, from 19.4 (7.6) mN/mm at 3 days to 11.3 (5.2) mN/mm at 7 days (p < .0001). Stiffness similarly decreased with local dexamethasone, from 25.9 (17.2) mN/mm at 3 days to 18.1 (13.0) mN/mm at 7 days (p < .0001). VF stiffness in the dexamethasone group was increased compared to tissues without local dexamethasone (p = .0002), and all groups with ETT placement had higher tissue stiffness at 3 days (p < .001). No significant change in histologic evidence of epithelial ulceration or fibrosis was noted, while an increased degree of inflammation was noted in the dexamethasone group (p = .04). Conclusion: Local dexamethasone delivery increases VF stiffness and degree of inflammation compared to uncoated ETTs in an acute laryngeal burn model, reflected in early biomechanical and histologic changes in an inhalational burn model.

Quantifying Intubation Forces on Incisors and Tongue Base Across Exposure Difficulty and Experience in a Simulator.

OBJECTIVE: Laryngoscopy simulators quantifying forces on critical structures in progressively challenging airways and operator expertise are lacking. We aimed to quantify laryngoscopy forces across expertise and exposure difficulty. STUDY DESIGN: Prospective observational study Setting: Tertiary care medical center Methods: Force gauges were affixed to a difficult airway mannequin to quantify teeth and tongue forces across increasingly challenging airway exposure. Medical students (n=10), residents (n=11), and otolaryngology staff (n=10) performed direct laryngoscopy using a Miller size 3 laryngoscope with 1) normal neck/jaw mobility, 2) restricted neck extension, 3) restricted jaw opening, and 4) restricted neck/jaw mobility. Incisor and tongue pounds of force (lbf) were continuously measured. RESULTS: As the difficulty setting increased, forces exerted by the students, residents, and staff on the incisors and tongue base increased (p=0.01). Between normal and maximally restricted settings, force delivered to the incisors increased by 6.95 lbf (standard error (SE) 1.29), 5.93 lbf (SE 0.98), and 5.94 lbf (SE 0.70) for the students, residents, and staff, respectively. At the tongue base, force increased by 0.37 lbf (SE 0.18), 0.46 lbf (SE 0.14), and 0.73 lbf (SE 0.15) for the students, residents, and staff, respectively. Esophageal intubations occurred in 50% of the students, 23% of the residents, and 45% of the otolaryngology staff at maximal difficulty, with none at the easiest setting (p=0.33). Compared to the residents, the staff applied significantly increased pressure on the tongue base during laryngoscopy (p=0.02). CONCLUSION: Forces exerted on the incisors and tongue base varied across exposure difficulty and expertise levels, suggesting that they may be useful markers for training and competence assessment.

Developing a Social Media Ontology Across Otolaryngology and its Subspecialties.

OBJECTIVE: To determine how social media is used in the dissemination of new information within otolaryngology, and to emphasize the importance of standardizing Twitter hashtag use. METHODS: Based on the 2019 SCImago journal rankings, the Twitter posts from the accounts of the top three journals covering each otolaryngology subspecialty were reviewed from August 1, 2020 to May 1, 2021. Twitter posts from the primary otolaryngology-related academic societies were also reviewed during this timeframe. A list of hashtags was generated based on a combination of the most common otolaryngologic procedures and most commonly used hashtags in the social media space. This list was then crowd-sourced with 10 fellowship-trained otolaryngologists for each subspecialty. RESULTS: Hashtag use among key stakeholders in the otolaryngology social media space varies considerably. For instance, #HNSCC, #HeadAndNeckSquamousCellCarcinoma, #HeadAndNeckCancer, #HeadAndNeckCancers, #OropharyngealCancer, #OropharynxCancer, #OralCancer, and #OPSCC were all commonly used hashtags to identify posts discussing oropharyngeal squamous cell carcinoma. #HeadAndNeckCancer and #HNSCC were most popular and used in a total of 85 and 65 tweets, respectively. #HeadAndNeckCancer was found alone in 32 out of 85 tweets (38%), whereas #HNSCC was found alone in 27 out of 65 tweets (42%). A standardized hashtag ontology covering all subspecialties within otolaryngology is proposed herein. CONCLUSIONS: Adoption of a standardized social media ontology within otolaryngology will improve information dissemination across all key stakeholders. Laryngoscope, 133:1595-1599, 2023.

A Novel Instrument Holder to Improve Operative Efficiency in Endoscopic Laryngeal and Airway Surgery.

OBJECTIVE: Receiving instruments from surgical technicians during endoscopic laryngeal and airway microsurgery (ELAM) has challenges including repeated, expeditious handling of delicate instruments and passing them to the surgeon's hand opposite of where the surgical assistant is standing. Optimizing this interaction may reduce surgical errors and improve operative efficiency. METHODS: A proprietary ELAM instrument holder was attached to both sides of the operating room bed. The device consisted of an articulating arm with custom silicone inserts mounted on a tray (storing up to three endoscopic instruments). ELAM cases were randomized to be performed either with (device) or without the holder (control). Using custom software, instrument pass time (IPT), instrument drop rate (IDR), and communication errors (eg handing incorrect instruments) were manually recorded. Qualitative use metrics relating to overall device satisfaction were also obtained. RESULTS: Data were collected from 25 device and 23 control cases among three different laryngologists. Average IPT was nearly three times quicker for the device (0.80 s, n = 1175 passes) compared with controls (2.09 s, n = 1208 passes) [p < 0.001]. IPT interquartile range was five times higher for control (1.65 s) versus device cases (0.42 s). IDR was not significantly different [p = 0.48]; however, device cases had significantly lower communication errors compared to control cases [p = 0.01]. Surgeons and surgical assistants were similarly satisfied with the device on a 5-point Likert scale (mean: 4.2/5, standard deviation: 0.92). CONCLUSION: The proposed endoscopic instrument holder can improve ELAM operative workflow by reducing instrument passing time and variability without increasing IDR. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3492-3498, 2023.

Scalable and High-Throughput In Vitro Vibratory Platform for Vocal Fold Tissue Engineering Applications.

The vocal folds (VFs) are constantly exposed to mechanical stimulation leading to changes in biomechanical properties, structure, and composition. The development of long-term strategies for VF treatment depends on the characterization of related cells, biomaterials, or engineered tissues in a controlled mechanical environment. Our aim was to design, develop, and characterize a scalable and high-throughput platform that mimics the mechanical microenvironment of the VFs in vitro. The platform consists of a 24-well plate fitted with a flexible membrane atop a waveguide equipped with piezoelectric speakers which allows for cells to be exposed to various phonatory stimuli. The displacements of the flexible membrane were characterized via Laser Doppler Vibrometry (LDV). Human VF fibroblasts and mesenchymal stem cells were seeded, exposed to various vibratory regimes, and the expression of pro-fibrotic and pro-inflammatory genes was analyzed. Compared to current bioreactor designs, the platform developed in this study can incorporate commercial assay formats ranging from 6- to 96-well plates which represents a significant improvement in scalability. This platform is modular and allows for tunable frequency regimes.

Longitudinal Effects of Base of Tongue Concurrent Chemoradiation Therapy in a Pre-Clinical Model.

BACKGROUND/OBJECTIVES: Base of tongue (BOT) dysfunction is common following oropharyngeal concurrent chemoradiation therapy (CCRT). We present a clinically relevant animal model quantifying the effects of CCRT on tongue strength and elasticity over time. METHODS: Fifty-three male and 53 female Sprague-Dawley rats were randomized to control or experimental groups. Experimental animals received cisplatin, 5-fluorouracil, and 5 fractions of 7 Gy directed to the BOT. Controls received no intervention. At 2 weeks, 5 months, or 10 months after CCRT, animals underwent non-survival surgery to measure twitch and tetanic tongue strength, which were analyzed using multivariate linear mixed effects models. Tongue displacement, a surrogate for tongue elasticity, was also determined via stress-strain testing and analyzed via a multivariate linear mixed effects model. RESULTS: Reporting the combined results of both sexes, the estimated experimental group mean peak twitch forces became more divergent over time compared to controls, being 8.3% lower than controls at 2 weeks post-CCRT, 15.7% lower at 5 months, and 31.6% lower at 10 months. Estimated experimental group mean peak tetanic forces followed a similar course and were 2.9% lower than controls at 2 weeks post CCRT, 20.7% lower at 5 months, and 27.0% lower at 10 months. Stress-strain testing did not find CCRT to have a significant effect on tongue displacement across experimental timepoints. CONCLUSIONS: This study demonstrates an increasing difference in tongue strength over time between controls and animals exposed to CCRT. Tongue elasticity was not significantly affected by CCRT, suggesting that changes in strength may not be caused by fibrosis. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1455-1461, 2023.

Characterization of Vocal Fold Pathology in Military Drill Instructors.

OBJECTIVE: Military drill instructors have extreme vocal demands that place them at risk for phonotrauma. Characterization of laryngeal pathology and vibratory characteristics among drill instructors presenting for specialized voice care is lacking. METHODS: A retrospective review in a specialized voice clinic over a two-year period was conducted. Patients identified as current drill instructors between the ages of 28-43 with a diagnosis of dysphonia were included. Laryngeal pathology was diagnosed by a fellowship trained laryngologist and vibratory characteristics were evaluated utilizing the Voice-Vibratory Assessment with Laryngeal Imaging (VALI) rating form. All patients were also evaluated by a speech-language pathologist. Patient reported outcome measures were collected along with perceptual voice evaluations utilizing the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V). RESULTS: Twelve current drill instructors were identified, and all had phonotraumatic lesions. Lesions were categorized as vocal fold hemorrhage (8%), ectasia (25%), unilateral epithelial thickening (33.3%), bilateral epithelial thickening (58.3%), ventricular cyst (8%), polyp (25%), and sulcus vocalis (25%). Vibratory abnormalities were assessed with the VALI rating scale and correlated to CAPE-V perceptual ratings with 83% having reduced mucosal wave, 75% reduced amplitude of lateral excursion, 50% aperiodic vibrations, 50% asymmetric or chasing wave, 58% glottal insufficiency, 100% supraglottic hyperfunction, and an average CAPE-V overall severity of 50% with severe perceptual dysphonia. The average Voice Handicap Index (VHI-10) and Reflux Symptom Index (RSI) score was 15.5 and 14.7, respectively. CONCLUSION: Phonotraumatic lesions were universally present in drill instructors complaining of hoarseness, suggesting early referral, and intervention may be warranted in this population. LEVEL OF EVIDENCE: 4.