Lott, David G.

Objectives/Hypothesis: Botulinum neurotoxin type-A (BoNT-A) injection into the true vocal cords is an effective treatment for restoring vocal functionality in adductor spasmodic dysphonia (AdSD). The Glasgow Benefit Inventory was developed to measure quality of life change following any otolaryngologic intervention and was recently revised to a 5-factor subdomain (GBI-5F) questionnaire to improve clinical utility. The study aim was to utilize the GBI-5F to measure patient-reported quality of life change in AdSD patients following BoNT-A injection. Methods: The GBI-5F questionnaire was administered to patients diagnosed with AdSD who received a BoNT-A vocal cord injection between December 2022 and May 2023. All patients had received multiple prior injections. GBI-5F subdomains and demographics were analyzed to identify areas for patient-reported improvement. Results: Sixty-six patients completed the GBI-5F. There were 52 (78.7%) females and average age was 69.4 years. The median total benefit score was +40.0 (interquartile range [IQR], 20.0). Median subdomain scores were +83.3 (IQR, 50.0) for quality of life, +50.0 (IQR, 50.0) for self-confidence, +33.3 (IQR, 33.3) for social involvement, +16.7 (IQR, 50.0) for support, and 0.0 (IQR, 16.7) for general health. Differences in the individual subdomain scores were statistically significant ( P < .0001). No significant differences were found in the total GBI-5F score or any subdomain according to sex or presence of vocal tremor (all P > .05). A moderately positive correlation was noted between median total score and percent functional improvement (r = 0.46, P < .001). Conclusion: Botulinum injection therapy for AdSD provides overall benefit to patients as measured by the GBI-5F, with particular improvement observed for perceived quality of life, self-confidence, and social involvement. Sex, presence/absence of vocal tremor, and age do not appear to modify benefit, though degree of functional improvement is positively correlated with total score.

Objectives/Goals: Aspiration causes or aggravates lung diseases. While bedside swallow evaluations are not sensitive/specific, gold standard tests for aspiration are invasive, uncomfortable, expose patients to radiation, and are resource intensive. We propose the development and validation of an AI model that analyzes voice to noninvasively predict aspiration. Methods/Study Population: Retrospectively recorded [i] phonations from 163 unique ENT patients were analyzed for acoustic features including jitter, shimmer, harmonic to noise ratio (HNR), etc. Patients were classified into three groups: aspirators (Penetration-Aspiration Scale, PAS 6–8), probable (PAS 3–5), and non-aspirators (PAS 1–2) based on video fluoroscopic swallow (VFSS) findings. Multivariate analysis evaluated patient demographics, history of head and neck surgery, radiation, neurological illness, obstructive sleep apnea, esophageal disease, body mass index, and vocal cord dysfunction. Supervised machine learning using five folds cross-validated neural additive network modelling (NAM) was performed on the phonations of aspirator versus non-aspirators. The model was then validated using an independent, external database. Results/Anticipated Results: Aspirators were found to have quantifiably worse quality of sound with higher jitter and shimmer but lower harmonics noise ratio. NAM modeling classified aspirators and non-aspirators as distinct groups (aspirator NAM risk score 0.528+0.2478 (mean + std) vs. non-aspirator (control) risk score of 0.252+0.241 (mean + std); p Discussion/Significance of Impact: We report the use of voice as a novel, noninvasive biomarker to detect aspiration risk using machine learning techniques. This tool has the potential to be used for the safe and early detection of aspiration in a variety of clinical settings including intensive care units, wards, outpatient clinics, and remote monitoring.

ABSTRACTMedical advances have enabled the realization of vascularized composite allografts and to date have demonstrated reasonably successful graft survival rates. Larynx and Trachea Transplantation (LT) has long been contemplated as a therapeutic option for severe laryngeal trauma and patients following total laryngectomy. Progress has been limited most likely due to lack of awareness as an option, technical and surgical expertise, limited transplant centers worldwide, need for multidisciplinary engagement from hospital leadership, Otolaryngology, and transplant medicine to build a successful program. As one of the first programs to exist in the United States, we have had to create new pathways, develop new workflows, work with numerous regulatory bodies, educate many people about the need for an LT, and learn many lessons along the way. The objectives of this paper are to help others navigate the complexities of creating a new LT transplant program so that this important treatment option may become more available to patients worldwide. We will provide a checklist for developing an LT program and discuss our experiences with the strategic development of an LT transplant program in an academic medical institution.

Abstract 3D printing, also known as additive manufacturing, holds immense potential for rapid prototyping and customized production of functional health‐related devices. With advancements in polymer chemistry and biomedical engineering, polymeric biomaterials have become integral to 3D‐printed biomedical applications. However, there still exists a bottleneck in the compatibility of polymeric biomaterials with different 3D printing methods, as well as intrinsic challenges such as limited printing resolution and rates. Therefore, this review aims to introduce the current state‐of‐the‐art in 3D‐printed functional polymeric health‐related devices. It begins with an overview of the landscape of 3D printing techniques, followed by an examination of commonly used polymeric biomaterials. Subsequently, examples of 3D‐printed biomedical devices are provided and classified into categories such as biosensors, bioactuators, soft robotics, energy storage systems, self‐powered devices, and data science in bioplotting. The emphasis is on exploring the current capabilities of 3D printing in manufacturing polymeric biomaterials into desired geometries that facilitate device functionality and studying the reasons for material choice. Finally, an outlook with challenges and possible improvements in the near future is presented, projecting the contribution of general 3D printing and polymeric biomaterials in the field of healthcare.

Abstract Recurrent respiratory papillomatosis (RRP) is a debilitating chronic disease of the airway caused by Human Papillomavirus (HPV). Here we describe the efficacy, safety, and immunogenicity from a Phase 1/2 trial of INO-3107, a DNA immunotherapy designed to elicit T-cell responses against HPV-6 and HPV-11, in adults with RRP (NCT04398433). Thirty-two eligible patients with HPV-6 and/or HPV-11 RRP, who required ≥2 surgical interventions in the year preceding dosing, were administered 4 doses of INO-3107 by intramuscular (IM) injection followed by electroporation (EP). The primary endpoint was safety and tolerability. Efficacy and immunology endpoints included the frequency of surgical interventions in the year following the first dose of INO-3107 and assessment of immune responses. The majority (26/32; 81%) of patients experienced a reduction in the number of surgeries in the year following initiation of treatment with INO-3107, when compared with the year prior. Peripheral blood assessments revealed HPV-6 and HPV-11 antigen-specific T-cell induction, inclusive of cytolytic CD8+ T-cells. RNA sequencing identified the presence of an inflammatory response in patient papillomas after treatment with INO-3107, inclusive of cytolytic CD8+ T-cell signatures. T-cell receptor sequencing revealed emergent T-cell clones in the blood and assessment of airway tissue confirmed trafficking of these clones to papillomas, which was associated with clinical benefit. Treatment was well tolerated, with 13/32 (41%) patients reporting a treatment-related adverse event (AE), all of which were low-grade. INO-3107 provides clinical benefit to adults with HPV-6 and/or HPV-11 associated RRP, is well tolerated, and generates an antigen-specific immune response against HPV. Importantly, treatment-induced peripheral T-cell responses traffick to airway tissue and are associated with clinical response, consistent with the proposed mechanism of action.

Objective: Recurrent respiratory papillomatosis (RRP) is a rare disease of the airway for which there is no known cure. Treatment involves the surgical removal or destruction of these lesions. There has been a long-standing debate over the effectiveness of the adjuvant intralesional injection of the immune modifying agent bevacizumab. This study is a systematic review investigating the effect of adjuvant intralesional bevacizumab on patients with laryngeal papillomatosis. The main objective was to assess functional outcomes and efficacy. Data Sources: Pubmed, Google Scholar, and Web of Science. Review Methods: Search words were “intralesional bevacizumab” AND “recurrent respiratory papillomatosis.” Sources were systematically identified using inclusion and exclusion criteria (ie, study publication must post-date 2000, must be peer-reviewed, investigate patients with RRP, apply bevacizumab intralesionally, not systemically). Findings were then collected and analyzed. Results: Ten studies were included for analysis. The majority of these studies found an increase in the surgical interval, voice outcomes, and a decrease in tumor burden in most patients. No studies reported side effects or lasting complications related to the bevacizumab injection. Conclusion: This systematic review provides further evidence for the safety of intralesional bevacizumab injections and their likely positive effect on disease control. Future research would benefit from the implementation of standardized documentation of RRP outcomes.

Objective To examine the impact of increased body mass index (BMI) on (1) tracheotomy timing and (2) short‐term surgical complications requiring a return to the operating room and 30‐day mortality utilizing data from the Multi‐Institutional Study on Tracheotomy (MIST). Methods A retrospective analysis of patients from the MIST database who underwent surgical or percutaneous tracheotomy between 2013 and 2016 at eight institutions was completed. Unadjusted and adjusted logistic regression analyses were used to assess the impact of obesity on tracheotomy timing and complications. Results Among the 3369 patients who underwent tracheotomy, 41.0% were obese and 21.6% were morbidly obese. BMI was associated with higher rates of prolonged intubation prior to tracheotomy accounting for comorbidities, indication for tracheotomy, institution, and type of tracheostomy ( p = 0.001). Morbidly obese patients (BMI ≥35 kg/m 2 ) experienced a longer duration of intubation compared with patients with a normal BMI (median days intubated [IQR 25%–75%]: 11.0 days [7–17 days] versus 9.0 days [5–14 days]; p < 0.001) but did not have statistically higher rates of return to the operating room within 30 days ( p = 0.12) or mortality ( p = 0.90) on multivariable analysis. This same finding of prolonged intubation was not seen in overweight, nonobese patients when compared with normal BMI patients (median days intubated [IQR 25%–75%]: 10.0 days [6–15 days] versus 10.0 days [6–15 days]; p = 0.36). Conclusion BMI was associated with increased duration of intubation prior to tracheotomy. Although morbidly obese patients had a longer duration of intubation, there were no differences in return to the operating room or mortality within 30 days. Level of Evidence 3 Laryngoscope , 134:4674–4681, 2024

ObjectivesThere is an absence of data in the literature regarding methods to improve the patient experience during the performance of awake in‐office laryngeal injections. This study sought to evaluate whether the use of local anesthetic or a vibrating instrument decreased overall pain experienced by patients with laryngeal dystonia, frequently referred to as spasmodic dysphonia (SD), undergoing transcervical botulinum toxin injections.MethodsThis was an unblinded, prospective randomized control trial with a crossover design where each patient received transcutaneous transcricothyroid injection of botulinum toxin with alternating use of no anesthesia, local anesthesia (2% lidocaine in 1:100,000 epinephrine), and vibrating instrument in three consecutive laryngeal injections to treat adductor SD. Patients were randomized to the order they received these treatments. Patients measured pain on a 0–10 visual analogue scale (VAS) and selected their preferred technique after receiving all three analgesic modalities.ResultsThirty‐two patients completed the study. There was no statistically significant difference in pain between the three analgesic techniques (p = 0.38). The most preferred analgesic technique was the vibrating wand (44% (14/32)). Lidocaine was the second most preferred (37% (12/32)) and 19% (6/32) of patients preferred nothing. When combining the wand and nothing groups, 63% of patients preferred one of these two methods (95% exact CI: 44%–79%).ConclusionThere was no statistically significant difference in median pain experienced by patients during laryngeal botulinum toxin injection between these different analgesic modalities. More than half of the patients selected a preference for a technique that did not include lidocaine. This data supports individualization of analgesia during transcutaneous laryngeal injections.Level of Evidence2 Laryngoscope, 134:2277–2281, 2024