Faculty Bibliography

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:Oral cancer causes intense pain at the primary site, and such pain can impair oral functions. However, the underlying mechanisms for oral cancer pain are still not fully understood. In the present study, it is investigated whether programmed cell death protein 1 (PD-1) is involved in the development of oral cancer pain. METHODS:RMP1-14, a specific anti-PD-1 antibody, was injected into spinal trigeminal nucleus caudalis (Sp5C) and measured pain behaviors using von Frey filaments and dolognawmeter. Western blotting and immunofluorescence staining were performed to analyze the expression of PD-1 and tumor necrosis factor alpha (TNFα) in the Sp5C. RESULTS:It was observed that the PD-1 antibody significantly inhibited mechanical hypersensitivity and functional allodynia in our oral cancer pain mouse model. Moreover, we found that TNFα was highly upregulated in the Sp5C following the induction of oral cancer pain and that intra-Sp5C injection of the PD-1 antibody diminished the upregulation of TNFα. It was found that genetic deletion of TNFα or its receptor antagonism synergized the analgesic effect of PD-1 antibody on oral cancer pain. CONCLUSION/CONCLUSIONS:Our results suggest that PD-1 in the Sp5C contributes to oral cancer pain by altering TNFα signaling in the trigeminal nociceptive system, and PD-1 could be targeted to develop a novel approach for oral cancer pain management.

Communication between intracellular organelles including lysosomes and mitochondria has recently been shown to regulate cellular proliferation and fitness. The way lysosomes and mitochondria communicate with each other (lysosomal/mitochondrial interaction, LMI) is, emerging as a major determinant of tumor proliferation and growth. About 30% of squamous carcinomas (including squamous cell carcinoma of the head and neck, SCCHN) overexpress TMEM16A, a calcium-activated chloride channel, which promotes cellular growth and negatively correlates with patient survival. We have recently shown that TMEM16A drives lysosomal biogenesis, but its impact on mitochondrial function has not been explored. Here, we show that in the context of high TMEM16A SCCHN, (1) patients display increased mitochondrial content, specifically complex I; (2) In vitro and in vivo models uniquely depend on mitochondrial complex I activity for growth and survival; (3) NRF2 signaling is a critical linchpin that drives mitochondrial function, and (4) mitochondrial complex I and lysosomal function are codependent for proliferation. Taken together, our data demonstrate that coordinated lysosomal and mitochondrial activity and biogenesis via LMI drive tumor proliferation and facilitates a functional interaction between lysosomal and mitochondrial networks. Therefore, inhibition of LMI instauration may serve as a therapeutic strategy for patients with SCCHN. Implications: Intervention of lysosome-mitochondria interaction may serve as a therapeutic approach for patients with high TMEM16A expressing SCCHN.

BACKGROUND:Accurate intraoperative diagnosis is crucial for differentiating between primary CNS lymphoma (PCNSL) and other CNS entities, guiding surgical decision-making, but represents significant challenges due to overlapping histomorphological features, time constraints, and differing treatment strategies. We combined stimulated Raman histology (SRH) with deep learning to address this challenge. METHODS:We imaged unprocessed, label-free tissue samples intraoperatively using a portable Raman scattering microscope, generating virtual H&E-like images within less than three minutes. We developed a deep learning pipeline called RapidLymphoma based on a self-supervised learning strategy to (1) detect PCNSL, (2) differentiate from other CNS entities, and (3) test the diagnostic performance in a prospective international multicenter cohort and two additional independent test cohorts. We trained on 54,000 SRH patch images sourced from surgical resections and stereotactic-guided biopsies, including various CNS neoplastic/non-neoplastic lesions. Training and test data were collected from four tertiary international medical centers. The final histopathological diagnosis served as ground-truth. RESULTS:In the prospective test cohort of PCNSL and non-PCNSL entities (n=160), RapidLymphoma achieved an overall balanced accuracy of 97.81% ±0.91, non-inferior to frozen section analysis in detecting PCNSL (100% vs. 77.77%). The additional test cohorts (n=420, n=59) reached balanced accuracy rates of 95.44% ±0.74 and 95.57% ±2.47 in differentiating IDH-wildtype diffuse gliomas and various brain metastasis from PCNSL. Visual heatmaps revealed RapidLymphoma's capabilities to detect class-specific histomorphological key features. CONCLUSIONS:RapidLymphoma proves reliable and valid for intraoperative PCNSL detection and differentiation from other CNS entities. It provides visual feedback within three minutes, enabling fast clinical decision-making and subsequent treatment strategy planning.

BACKGROUND AND OBJECTIVES/OBJECTIVE:The management of World Health Organization (WHO) grade 2 meningiomas is complicated by their diverse clinical behaviors. Stereotactic radiosurgery (SRS) can be an effective management option. Literature on SRS dose selection is limited but suggests that a higher dose is better for tumor control. We characterize the predictors of post-SRS outcomes that can help guide planning and management. METHODS:We reviewed a cohort of consecutive patients with pathologically-proven WHO grade 2 meningiomas who underwent SRS at a single institution between 2011 and 2023. RESULTS:Ninety-nine patients (median age 62 years) underwent SRS, 11 of whom received hypofractionated SRS in 5 fractions. Twenty-two patients had received previous irradiation. The median follow-up was 49 months. The median overall survival was 119 months (95% CI 92-NA) with estimated 5- and 10-year survival of 83% and 27%, respectively. The median progression-free survival (PFS) was 40 months (95% CI 32-62), with 3- and 5-year rates at 54% and 35%, respectively. The median locomarginal PFS was 63 months (95% CI 51.8-NA) with 3- and 5-year rates at 65% and 52%. Nine (9%) patients experienced adverse events, 2 Common Terminology Criteria for Adverse Events grade 3 and 7 grade 2, consisting of worsening neurologic deficit from edema. In the single-session cohort, Ki-67 significantly predicted both overall survival and intracranial PFS. Tumors with Ki-67 >10% had 2.17 times the risk of locomarginal progression compared with Ki-67 ≤10% (P = .018) adjusting for covariates. Sex, prescription dose, tumor volume, and location also predicted tumor control. In tumors with Ki-67 >10%, margin dose ≥14 Gy was associated with significantly better tumor control but not for tumors with Ki-67 ≤10%. CONCLUSION/CONCLUSIONS:The management of WHO grade 2 meningiomas requires a multimodality approach. This study demonstrates the value of a targeted SRS approach in patients with limited disease and further establishes predictive biomarkers that can guide planning through a personalized approach.

OBJECTIVE:To compare salivary flow rates between females and males, before and after radiation therapy (RT) for head and neck cancer (HNC). METHODS:Prospective observational multicenter cohort study (OraRad). Stimulated whole salivary flow was measured before RT and at 6 and 18 months after RT. RESULTS:Mean (95% confidence interval) salivary flow in g/min before RT was 0.81 (0.71, 0.90) in females (n = 107) and 1.20 (1.15, 1.25) in males (n = 391) (p < 0.001); at 6 months was 0.34 (0.24, 0.44) in females and 0.50 (0.44, 0.55) in males (p = 0.01); at 18 months was 0.49 (0.38, 0.59) in females and 0.70 (0.64, 0.75) in males (p < 0.001). Median nadir salivary flow after RT was 0.22 in females and 0.35 in males (p < 0.001). A lower nadir salivary flow in females, but not males, was associated with an increased risk for tooth failure (p = 0.02). CONCLUSIONS:Females with HNC have lower stimulated whole salivary flow than males, before and after RT. Low salivary flow after RT may be a risk factor for tooth failure among females. The lower pre-RT salivary flow rates in females, combined with prior literature in other populations, indicates that, in general, females have lower stimulated salivary flow than males.

PURPOSE/OBJECTIVE:Mental health disorders, substance abuse, and tobacco use are prevalent in the US population. However, the association between these conditions and head and neck cancer (HNC) stage is poorly understood. This research aims to uncover the relationship between pre-existing mental health disorders, substance abuse, and tobacco use and HNC stage at diagnosis in patients receiving care in an integrated, public safety-net healthcare system. METHODS:This study was a secondary data analysis of linked hospital tumor registries and electronic health record (EHR) data. The study's primary independent variables were the comorbidities of mental health disorders, substance abuse, and tobacco use. The dependent variable was HNC stage at diagnosis, operationalized as early stage (i.e., stages I, II, and III) and advanced stage (stage IV, IVA, IVB, or IVC). The analysis included multivariable logistic regression adjusted for covariates of demographic variables, tumor anato RESULTS: The study population consisted of 357 patients with median age of 59 years, and was primarily male (77%), diverse (Black or African American 41%; Hispanic 22%), and from neighborhoods with low income (median average annual household income $39,785). Patients with a history of mental health disorders with or without tobacco use had significantly lower odds of advanced stage HNC at diagnosis (adjusted OR = 0.35, 95% Confidence Interval [CI]: 0.17-0.72.) while patients with a history of substance abuse with or without tobacco use had significantly higher odds of advanced stage HNC at diagnosis (adjusted OR 1.41, 95% CI: 1.01-1.98) than patients with no history of mental health disorders, substance abuse, or tobacco use. CONCLUSIONS:The relationship between HNC stage at diagnosis and the comorbidities of mental health disorders, substance abuse, or tobacco differs depending on the type and co-occurrence of these comorbidities. These findings demonstrate the need for innovative care delivery models and education initiatives tailored to meet the needs of patients with mental health disorders, substance abuse, and tobacco use that facilitate early detection of HNC.

INTRODUCTION/BACKGROUND:The COVID-19 pandemic necessitated a rapid restructuring of the clinical management of voice and upper airway disorders by speech-language pathologists (SLPs). As in-person therapy sessions were suspended, voice-specialized SLPs across healthcare settings shifted to online teletherapy. In this survey study, we queried voice therapists on their experiences with and opinions regarding the adoption of teletherapy into routine clinical practice. METHODS:Voice-specialized SLPs were recruited nationwide to complete an online survey which included questions about the usability of software and hardware, patient management, the effectiveness of therapy, overall satisfaction, and suggestions for improvement. RESULTS:48 participants completed the survey. The majority of respondents reported frequent technical difficulties and poor access to or understanding of appropriate equipment. Overall, participants endorsed better patient access, attendance, and compliance, as well as increased scheduling flexibility. While 95% of the respondents stated they would recommend teletherapy to another SLP, only 20% supported a shift to exclusively virtual sessions. Forty percent of respondents endorsed a hybrid model consisting of initial in-person sessions followed by virtual ones. DISCUSSION/CONCLUSIONS:Incorporating teletherapy into clinical voice practice has, for the most part, followed Carl May's normalization process theory framework, in that clinicians have invested understanding, training, time and effort, and appraisal into its implementation. However, the unusually rapid pace of change necessitated by the pandemic has presented its own set of challenges. Given the inherent conveniences of virtual therapy, the online modality is likely here to stay. It is critical that we understand the facilitators and barriers to its successful adoption.

Deep plane facelift surgery is not new, having originally been described over 30 years ago, however the technique has seen a recent surge in popularity. While proponents emphasize its ability to deliver very natural results, critics often cite the possibility of additional risk of the procedure due to its technically challenging dissection in proximity to branches of the facial nerve and other critical structures. These risks are perhaps greatest when operating in what have historically been described as the "danger zones," particularly when releasing the zygomatic retaining ligaments, when performing the medial deep plane dissection in the midface, and when extending the platysma flap over the angle of the mandible into the neck. The senior author (DBR) has performed deep plane facelift surgery for over 20 years, training many novice surgeons to perform this procedure safely and incrementally. Herein, we illustrate surgical techniques to optimize safety when performing deep plane dissections. A novel vertical midline platysmaplasty combined with extended release of the low cervical platysma provide rejuvenation of the neck that extends to the clavicles.