Faculty Bibliography

BACKGROUND:Human papillomavirus (HPV) negative oropharyngeal squamous cell carcinoma (OPSCC) is associated with worse survival when compared to HPV-positive OPSCC. Primary surgery is one option to intensify therapy in this high-risk group of patients. Unfortunately, the only randomized trial to explore this approach (RTOG 1221) failed to accrue and the role of primary surgery in the treatment of HPV-negative OPSCC remains unanswered. METHODS:A systematic review and meta-analysis were performed to examine the outcomes of surgery in the treatment of HPV-negative OPSCC. We used the PRISMA statement for reporting and queried Pubmed, Web of Science and the Cochrane databases for studies examining the use of primary surgery in the treatment of HPV-negative OPSCC. Excluded from analysis were reviews, commentaries, case series with fewer than 10 patients, and studies that included HPV-negative head and neck cancers of mixed sites. Our primary outcomes were 2-year and 5-year overall survival (OS) and disease-free survival (DFS). OS and DFS were pooled using meta-analysis of proportions. RESULTS: = undetermined; 2 studies). CONCLUSIONS:The two- and five-year OS for patients with HPV-negative OPSCC treated with any surgical approach and pathology-directed adjuvant therapy is 84% and 72%, respectively. The two- and five-year OS for HPV-negative OPCSCC treated with transoral surgery and pathology-directed adjuvant therapy is 87% and 82%, respectively.

PURPOSE/UNASSIGNED:Most auditory-perceptual voice research utilizes the judgments of trained listeners rather than everyday listeners with no previous training in speech pathology. Online crowdsourcing of behavioral data from untrained participants is rapidly increasing in popularity but has yet to be a common procedure for auditory-perceptual studies of the voice. The objective of this pilot study was to assess the functionality of this model for judgments of voice by using an online experiment platform to replicate a lab-based, voice-specific age estimation study. METHOD/UNASSIGNED:Fifty crowdsourced untrained listeners estimated the age of a single talker based on audio samples taken from 20 speeches over a 48-year span. The primary outcome was overall age estimation accuracy. RESULTS/UNASSIGNED:The crowdsourced age estimations closely matched those of a previous highly controlled in-person laboratory study using the same auditory samples. Listeners generally overestimated the talker's age when the talker was younger and underestimated his age when he was older. The age at which the estimated age equaled the talker's chronological age was 54 years. CONCLUSIONS/UNASSIGNED:Online crowdsourcing may be a feasible modality for auditory-perceptual voice ratings with the potential to add low-cost, high-number options to validate and enhance clinical and laboratory-based studies by (a) including a wider diversity of participants and (b) providing the means for rapidly recruiting more participants. Further research investigating crowdsourced ratings of the complex parameters of voice quality using more listeners is needed to continue supporting this methodology as a tool for perceptual voice research.

BACKGROUND:Aneurysmal bone cysts (ABCs) are slow-growing, expansile bone tumors most often observed in the long bones and lumbar and thoracic spine. Anterior column ABCs of the spine are rare, and few cases have described their surgical management, particularly for lesions with extension into the odontoid process and the bilateral C2 pedicles. In the present case, the authors describe a two-stage strategy for resection of a symptomatic 2.3 × 3.3 × 2.7-cm C2 ABC with cord compression in a 13-year-old patient. OBSERVATIONS/METHODS:Initial tumor debulking was completed via a transoral approach, and resection of the involved region spanning the odontoid process to the C2-3 disc space was continued until visualization of the posterior longitudinal ligament. After appropriate decompression was confirmed, the patient was repositioned prone for removal of the residual tumor among the bilateral C2 pedicles. Posterior instrumentation was placed from the occiput to C4, with an autologous rib graft to encourage fusion. The postoperative recovery was uneventful, and 2-month imaging demonstrated postsurgical changes, resolution of compression, and a stable position of the instrumentation and graft material. LESSONS/CONCLUSIONS:The transoral approach facilitates sufficient exposure for the resection of large odontoid ABCs, and posterior stabilization can reduce the risk of postsurgical cervical subluxation. https://thejns.org/doi/10.3171/CASE2485.

Vertebrates stabilize gaze using a neural circuit that transforms sensed instability into compensatory counterrotation of the eyes. Sensory feedback tunes this vestibulo-ocular reflex throughout life. We studied the functional development of vestibulo-ocular reflex circuit components in the larval zebrafish, with and without sensation. Blind fish stabilize gaze normally, and neural responses to body tilts mature before behavior. In contrast, synapses between motor neurons and the eye muscles mature with a time course similar to behavioral maturation. Larvae without vestibular sensory experience, but with mature neuromuscular junctions, had a strong vestibulo-ocular reflex. Development of the neuromuscular junction, and not sensory experience, therefore determines the rate of maturation of an ancient behavior.

INTRODUCTION/BACKGROUND:Glucocorticoids (GCs) are commonly prescribed for laryngeal indications due to their potent anti-inflammatory properties. However, GCs effect on vocal fold (VF) epithelial morphology and barrier function following injury is overlooked and may be key to efficacy. In this study, the effects of GCs on epithelial morphology and barrier function were quantified in injured VFs. We seek to increase our understanding of biochemical processes underlying GC mechanisms to refine therapeutic strategies. METHODS:Microflap injury was induced in 65 rabbits. Seven days after injury, animals received bilateral 20 μL intracordal injections of saline, dexamethasone, methylprednisolone, or triamcinolone (n = 15 per condition). Five rabbits in each condition were euthanized 1, 7, or 60 days following treatment. An additional five animals served as non-injured/untreated controls. To quantify transepithelial electrical resistance (TEER), 1 mm epithelial biopsies were placed in an Ussing chamber. The contralateral VF was processed for transmission electron microscopy and epithelial depth analysis. RESULTS:At 60 days, GC treatment maintained TEER levels similar to non-injured/untreated controls. However, triamcinolone reduced TEER compared with saline-treated conditions. Acutely, epithelial hyperplasia typically persisted in all injured VFs. At 60 days, only dexamethasone and triamcinolone increased epithelial depth in injured VFs; all GCs increased epithelial depth compared with non-injured/untreated controls. CONCLUSION/CONCLUSIONS:Acutely, GCs did not alter TEER. Additionally, GCs did not alter epithelial depth compared with saline treatment, indicating alignment with natural healing responses. At 60 days, GCs exhibited varying degrees of TEER restoration and epithelial hyperplasia, possibly due to distinct pharmacodynamic profiles. LEVEL OF EVIDENCE/METHODS:NA Laryngoscope, 2024.

BACKGROUND:Racial and ethnic disparities in thyroid cancer care may be mitigated by improving enrollment of more diverse patient populations in clinical trials. We studied trial eligibility criteria and enrollment to assess barriers to equitable representation. METHODS:ClinicalTrials.gov was searched for studies on thyroid cancer treatment conducted between 1993 and 2023. The inclusion and exclusion criteria of each study were examined. For published studies, reported demographic information was collected. Observed enrollment by race was compared with the expected distribution as determined using data from the US Census and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) databases. Over- and under-representation was defined as the ratio of observed to expected (O/E) enrollment by the race and ethnicity group. RESULTS:Of 309 thyroid cancer-related trials, 23 (7.4%) used language as an exclusion criterion. Most were interventional (n = 239, 77.3%), university-initiated (194, 62.8%), and drug/device-focused (195, 63.1%). Of studies that excluded by language, 20 (87.0%) were university-initiated. Eighty-eight trials were subsequently published, with 16 (18.2%) reporting race and/or ethnicity distributions. When comparing O/E ratios, White American participants were over-represented (O/E ratio: 1.2, P < .0001). Under-represented groups included Asian/Native Hawaiian (O/E ratio: 0.6, P = .0085), Black (0.6, P = .014), Native American (0.2, P = .072), and Hispanic patients (0.2, P < .0001). CONCLUSION/CONCLUSIONS:Over the last 3 decades, 1 in 13 thyroid cancer-related clinical trials excluded patients based on language. In the fraction of published studies to report on racial and ethnic demographics, Asian/Native Hawaiian, Black, and Hispanic patients were under-represented. Improved reporting of demographics in published studies and elimination of exclusion criteria such as language that hinder enrollment of minority patients could improve equitable representation of patients in thyroid cancer clinical trials.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:An increasing number of older adults are seeking behavioral voice therapy to manage their voice problems. Poor adherence to voice therapy is a known problem across all treatment-seeking populations. Given age-related physical and cognitive impairments and multiple chronic conditions, older adults are more susceptible to low adherence to behavioral therapies. The purpose of this study was to test the feasibility of an at-home, vocal training intervention for older adults without a known voice disorder living in a senior living community, as well as compare the effects of two modes of mobile health (mHealth) technology-assisted vocal training targeting vocal function and adherence in older adults. STUDY DESIGN/METHODS:Cohort Study (Prospective Observational Study). METHODS:Twenty-three individuals were recruited from a single residential retirement community and randomly allocated into two experimental groups. Both groups were asked to practice the Vocal Function Exercises with increasing frequency over an 8-week period. Tablets with instructions for performing the exercises were provided to all participants. The feedback group's tablets also contained an application providing real-time feedback on pitch, loudness, and duration. Acoustic and aerodynamic measures of vocal function and cognitive measures were obtained before and after the intervention. Self-reported measures of practice frequency, perceived vocal progress and changes, and motivation were obtained weekly. RESULTS:The feedback control group adhered to the requested practice sessions more in the latter half of the intervention (weeks 5 and 8). Vocal function measures remained stable. Overall, a pattern reflecting self-reported vocal progress and a general improvement in working memory and global cognitive functioning was observed in the feedback group. CONCLUSIONS:This study demonstrated that an 8-week mHealth intervention is viable to facilitate vocal practice in older adults. Although vocal ability did not improve with training, results indicated that vocal performance remained stable and age-related vocal changes did not progress. Future research on implementation of mHealth applications in conjunction with behavioral voice therapy is warranted to assess adherence and improvements in vocal function in individuals with age-related voice problems.

OBJECTIVE:This study aims to evaluate the clinical outcomes of patients receiving in-office vocal fold steroid injections (VFSI), highlighting relatively new measures around vocal pitch. METHODS:Patients with a diagnosis of vocal fold scar who received in-office VFSI from 2013 to 2024 were evaluated. Pre- and post-steroid Voice Handicap Index (VHI-10) scores, stroboscopic vibratory parameters, acoustic measures of cepstral peak prominence (CPP), and fundamental frequency coefficient of variation (F0CoV) during sustained phonation were analyzed using Wilcoxon signed-rank tests and McNemar's tests. RESULTS:Twenty-two patients had follow-up data 1-3 months after steroid injection. The median decrease in VHI-10 after one injection was 4 points (p = 0.02). We found no difference in CPP and F0CoV measures at follow-up. Forty-five percent of patients improved in mucosal wave and amplitude of at least one vocal fold. Earlier presentation from vocal injury was associated with improvement in mucosal wave and amplitude of the left vocal fold (p = 0.03). We found no difference in sex, tobacco smoking history, singing status, secondary diagnosis, and baseline VHI-10 score between patients who improved in vibratory parameters and those who did not. CONCLUSION/CONCLUSIONS:This single-center study is one of the largest exploring patient outcomes following in-office VFSI. Though patients reported modest improvement in voice use after VFSI, this may not be as impactful as previously believed. Improvement in videostroboscopy is expected in about half of the patients, with recency from vocal injury a likely predictor of success. These partially negative results provide insight into counseling patients regarding benefits from in-office VFSI. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2024.

BACKGROUND:Patient electronic messaging has increased clinician workload contributing to burnout. Large language models can respond to these patient queries, but no studies exist on large language model responses in thyroid disease. METHODS:This cross-sectional study randomly selected 33 of 52 patient questions found on Reddit/askdocs. Questions were found through a "thyroid + cancer" or "thyroid + disease" search and had verified-physician responses. Additional responses were generated using ChatGPT-3.5 and GPT-4. Questions and responses were anonymized and graded for accuracy, quality, and empathy using a 4-point Likert scale by blinded providers, including 4 surgeons, 1 endocrinologist, and 2 physician assistants (n = 7). Results were analyzed using a single-factor analysis of variance. RESULTS:For accuracy, the results averaged 2.71/4 (standard deviation 1.04), 3.49/4 (0.391), and 3.66/4 (0.286) for physicians, GPT-3.5, and GPT-4, respectively (P < .01), where 4 = completely true information, 3 = greater than 50% true information, and 2 = less than 50% true information. For quality, the results were 2.37/4 (standard deviation 0.661), 2.98/4 (0.352), and 3.81/4 (0.36) for physicians, GPT-3.5, and GPT-4, respectively (P < .01), where 4 = provided information beyond what was asked, 3 = completely answers the question, and 2 = partially answers the question. For empathy, the mean scores were 2.37/4 (standard deviation 0.661), 2.80/4 (0.582), and 3.14/4 (0.578) for physicians, GPT-3.5, and GPT-4, respectively (P < .01), where 4 = anticipates and infers patient feelings from the expressed question, 3 = mirrors the patient's feelings, and 2 = contains no dismissive comments. Responses by GPT were ranked first 95% of the time. CONCLUSIONS:Large language model responses to patient queries about thyroid disease have the potential to be more accurate, complete, empathetic, and consistent than physician responses.