Faculty Bibliography

OBJECTIVE:The videofluoroscopic swallow study (VFSS) is an evaluation of the anatomy and physiology of swallowing, and often includes a screening evaluation of the esophagus. How the esophageal screen translates to esophageal pathology remains unknown. The purpose of this study was to determine if abnormal esophageal clearance (EC) on VFSS correlates with esophageal function on high-resolution esophageal manometry (HREM). MATERIALS AND METHODS/METHODS:This is a retrospective review of 115 adult patients who underwent both VFSS with esophageal screen and HRM. EC on VFSS was scored with the modified barium swallow impairment profile (MBSImP) component 17. Motility was characterized using HRM metrics according to the Chicago Classification Version 4.0 (CCv4.0). Predictive metrics were calculated for the esophageal screen. RESULTS:An EC score o greater than or equal to 1 had a sensitivity of 66%, specificity of 57%, PPV of 52%, NPV of 70%, and OR of 2.55 (p = 0.027). EC weakly correlated with incomplete bolus clearance (rho = 0.331, p = 0.0004) and did not correlate with bolus transit time (rho = 0.17, p = 0.105). CONCLUSIONS:The esophageal screen as characterized by the MBSImP is not an effective predictor of esophageal function on HREM as defined by the CCv4.0. Future work may focus on a defining a standardized VFSS protocol for the esophageal screen and potentially a more nuanced assessment of esophageal findings on VFSS that may enhance the sensitivity of the modality to motility disorders.

Oropharyngeal dysphagia is an independent predictor of poor outcomes in many health conditions and can be targeted directly through swallowing therapy. This study aims to explore the outcomes of outpatient swallowing therapy in clinical practice across a diverse cohort of patients. This was a retrospective, single-site longitudinal cohort study. Patients 18 years or older with dysphagia who completed 7-8 weeks of outpatient swallowing therapy with a pre- and post-treatment videofluoroscopy were included. Therapy employed a progressive swallowing exercise regimen based on the Systematic Exercise for Treatment of Swallowing (SETS) protocol. Outcome measures included the pharyngeal components of the Modified Barium Swallow Impairment Profile, penetration-aspiration scale scores, and diet recommendations using the International Dysphagia Diet Standardization Initiative. 152 patients were included. Swallowing therapy improved all MBSImP component scores except 1, 7, and 13. Therapy improved total pharyngeal impairment scores by 2.66 points (p < .001) and total oral impairment score by 1.41 points (p < .001). Odds of elevated aspiration risk were reduced by 49% (p < .001). Patients were more likely to be on an unmodified food consistency after completion of therapy (OR 26, p = .004), but liquid consistency was not altered (OR 2.0, p = .57). Overall, 44% of patients in the cohort with an efficiency issue improved, and 50% of patients at risk for aspiration pre-therapy improved. Completing a 7-8 week course of exercise-based outpatient swallowing therapy is effective at improving multiple measures of swallowing physiology, safety and efficiency. It can also enable relaxation of diet consistency restrictions based on the IDDSI framework.

PURPOSE/OBJECTIVE:Dysphagia is a commonly occurring medical condition estimated to occur in between and 10% adults in the US. Despite this relatively high prevalence, the general population's understanding of this condition is currently unknown. Our aims were to (a) conduct a large-scale survey to determine the public's awareness and understanding of dysphagia in comparison to other three other health conditions and (b) compare this knowledge to relative prevalence rates of the conditions. METHODS:The survey was designed to measure four constructs of interest comparing dysphagia with insomnia, vertigo and ataxia. Constructs included: (1) Knowledge of the Condition, (2) Source of Knowledge, (3) Health Impact, (4) Treating Medical Professionals. The survey was launched via Qualtrics™ software and participants were recruited and paid using Prolific™. Descriptive statistics were used to compare participants knowledge of dysphagia with the other conditions. To obtain relative prevalence rates, Cosmos was used to quantify the number of Epic-based patient encounters with any ICD-10 code for each condition in 2023 and expressed as a percent of all patient encounters in the US in 2023. RESULTS:2000 adults (n = 1030 female) aged 18-95 (median 49, IQR = 33-62) completed our survey. When asked, 'Do you know what ____ is'? participants expressed higher familiarity with insomnia (99%) and vertigo (87%) in comparison to dysphagia (25%) and ataxia (18%). From a list of 8 options, 99% and 94% participants selected the correct impairment for insomnia and vertigo respectively, compared with 44% correct for dysphagia and 22% for ataxia. Participants selected an appropriate healthcare provider for dysphagia 47% of the time compared with 74% for insomnia, 56% for vertigo and 36% for ataxia. When asked to identify up to 3 sequelae (from a list of 9), only 4% of participants were able to correctly identify all three for dysphagia, in comparison to 16% for ataxia, 27% for vertigo and 60% for insomnia. The Cosmos analysis revealed that while insomnia had the highest prevalence in 2023 (5.5% of patient encounters), dysphagia occurred much more frequently (2.4%) than vertigo (0.68%) and ataxia (0.24%). CONCLUSIONS:These discrepancies highlight a notable gap in public awareness between dysphagia and more recognized conditions of insomnia and vertigo, even though the prevalence of dysphagia is higher than vertigo. Increasing public awareness of dysphagia is vital for early intervention, increasing quality of life, and advocating for equitable access to healthcare resources.

BACKGROUND:Four-dimensional computed tomography is routinely used to localize parathyroid disease, with consistently excellent parathyroid gland localization rates reported. This study evaluated whether pairing 4-dimensional computed tomography results with preoperative clinical variables can accurately predict single-gland disease in primary hyperparathyroidism. METHODS:Patients with primary hyperparathyroidism who underwent both 4-dimensional computed tomography imaging and parathyroidectomy between January 2019 and September 2021 at a large academic health system were included. Patient demographics, preoperative characteristics, and peri- and postoperative data were collected. The accuracy of 4-dimensional computed tomography in correctly identifying patients with single-gland disease with and without preoperative calcium and parathyroid hormone levels was calculated. Single-gland disease was defined by intraoperative parathyroid hormone decrease >50% and a hypercellular gland on pathology. RESULTS:One hundred seventy-five patients had 4-dimensional computed tomography results suggestive of single gland disease. One hundred fifty-two patients (87%) were predicted correctly to have single-gland disease. The predictive accuracy increased when stratifying by preoperative calcium (≥10.5 mg/dL, ≥11 mg/dL, and ≥12 mg/dL) and parathyroid hormone levels (≥65 pg/mL, ≥100 pg/mL, and ≥200 pg/dL). The accuracy further increased when stratifying by age (≤50 years). Accuracy for single gland disease was 100% when combined with any of the following: (1) calcium ≥12 mg/dL, (2) parathyroid hormone ≥200 pg/dL, or (3) calcium ≥11 mg/dL in patients ≤50 years. CONCLUSION/CONCLUSIONS:Four-dimensional computed tomography alone accurately predicted single gland disease in 87% of patients with primary hyperparathyroidism. When combined with preoperative calcium, parathyroid hormone and age thresholds, predictive accuracy for single-gland disease approached 100%. Given the high likelihood of single-gland disease in these scenarios, clinicians may consider offering focused unilateral parathyroidectomy without intraoperative parathyroid hormone monitoring in selected patients.

Cortical networks for the production of spoken language in humans are organized by phonetic features^1,2, such as articulatory parameters^3,4 and vocal pitch^5,6. Previous research has failed to find an equivalent forebrain representation in other species^7-11. To investigate whether this functional organization is unique to humans, here we performed population recordings in the vocal production circuitry of the budgerigar (Melopsittacus undulatus), a small parrot that can generate flexible vocal output^12-15, including mimicked speech sounds¹⁶. Using high-density silicon probes¹⁷, we measured the song-related activity of a forebrain region, the central nucleus of the anterior arcopallium (AAC), which directly projects to brainstem phonatory motor neurons^18-20. We found that AAC neurons form a functional vocal motor map that reflects the spectral properties of ongoing vocalizations. We did not observe this organizing principle in the corresponding forebrain circuitry of the zebra finch, a songbird capable of more limited vocal learning²¹. We further demonstrated that the AAC represents the production of distinct vocal features (for example, harmonic structure and broadband energy). Furthermore, we discovered an orderly representation of vocal pitch at the population level, with single neurons systematically selective for different frequency values. Taken together, we have uncovered a functional representation in a vertebrate brain that displays unprecedented commonalities with speech-related motor cortices in humans. This work therefore establishes the parrot as an important animal model for investigating speech motor control and for developing therapeutic solutions for addressing a range of communication disorders^22,23.

Rat ultrasonic vocalizations (USVs) have traditionally been used in psychosocial and psychobiological studies to understand emotion, social behavior, cognition, and associative learning. However, recent studies have expanded the goal of USVs to include the study of the laryngeal system and the effects of disease processes on vocal sensorimotor control. Without the foundational understanding of the goals of this area of laryngological research, fundamental differences in study objectives between psychobehavioral and laryngological studies can easily be missed, leading to misconceptions and misinterpretations of the role USVs play in laryngology-focused studies. Standardization of terminology and methods are also needed to improve communication, enhance study replicability, and prevent ambiguity that can lead to misinterpretations of study objectives and findings in this line of research. The primary objective is to describe the role of USVs in studies of laryngeal anatomy and physiology, with a focus on their connections to the neuromuscular and neurological aspects of the laryngeal system, particularly in relation to vocal sensorimotor control and voice disorders. It is intended for novice investigators interested in laryngology-specific USV research. Researchers experienced in USV studies within the context of the larynx and vocal sensorimotor control first outline the development and refinement of various USV elicitation methods. They provide insights into how these approaches have been tested across different studies and laboratories. Finally, they advocate for standardizing terminology and methodologies to enhance study replicability, reduce ambiguity, and foster collaboration across research groups.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:This study investigated the effects of the "crack-sob" onset-a distinctive vocal technique combining a sob gesture with an intentional pitch break-on vocal fold function during high-intensity singing. We hypothesized that this onset would either decrease glottal adduction and increase vocal fold vibration stability or alternatively, show no measurable effects while still providing perceived benefits to singers. STUDY DESIGN/METHODS:Prospective observational cohort study. METHODS:Twenty professional musical theatre singers (10 male, 10 female) performed high-intensity sustained notes with and without the crack-sob onset using both a control phrase and self-selected repertoire. Electroglottography measured contact quotient (CQ) and its relative standard deviation (relSDCQ). Acoustic analysis quantified smoothed cepstral peak prominence (CPPS), harmonics-to-noise ratio (HNR), and vocal intensity (dB SPL). Linear mixed effects modeling was used to analyze the effects of the crack-sob maneuver, with sex and vocal phrase as covariates. RESULTS:The crack-sob onset showed no significant effects on any measured parameters. CQ remained consistent at 66% regardless of onset type. No significant changes were observed in CPPS, dB SPL, relSDCQ, or HNR when using the crack-sob onset, with all effect sizes below 0.1. Significant differences were found between control and self-selected phrases, with the control phrase showing higher CPPS (+2.6 dB), intensity (+2.7 dB SPL), and HNR (+4.3). CONCLUSIONS:The crack-sob onset does not significantly alter objective measures of vocal fold adduction or vibratory stability during sustained high-intensity phonation in trained singers. The technique's reported benefits may be primarily perceptual rather than physiological, suggesting its value as a pedagogical tool for managing singer effort without compromising vocal function.

We leverage a clinical trial (NCT04080804) that compared neoadjuvant anti-PD-1, anti-PD-1+CTLA-4, and anti-PD-1+LAG-3 therapies in head and neck squamous cell carcinoma patients. Combination therapies promote higher pathologic response rates versus monotherapy, and major pathologic response is associated with better survival. To address whether successful immune checkpoint inhibitor (ICI) regimens act through similar or distinct pathways, we robustly and longitudinally characterize transcriptional and proteomic dynamics of CD8⁺ tumor-infiltrating lymphocytes (TILs) in a clonal manner. Anti-PD-1+LAG-3 reprograms CD8⁺ TIL with type-I interferon response and exhaustion gene programs into effector memory and resident memory (T_EM/T_RM). In contrast, anti-PD-1+CTLA-4 activates and expands pre-existing T_EM/T_RM CD8⁺ TIL, but does not rejuvenate exhausted phenotypes into T effector cells. Anti-PD-1+LAG-3, but not anti-PD-1+CTLA-4, induces widespread TCR sharing among the different transcriptional states, as well as increased TCR diversity in responding patients. Our data suggest doublet regimen-specific transcriptional and clonal dynamics of tumor-reactive CD8⁺ T cells.

Embryonic development in many species, including case reports in humans, can be temporarily halted before implantation during a process called diapause. Facultative diapause occurs under conditions of maternal metabolic stress such as nursing. While molecular mechanisms of diapause have been studied, a natural inducing factor has yet to be identified. Here, we show that oxytocin induces embryonic diapause in mice. We show that gestational delays were triggered during nursing or optogenetic stimulation of oxytocin neurons simulating nursing patterns. Mouse blastocysts express oxytocin receptors, and oxytocin induced delayed implantation-like dispersion in cultured embryos. Last, oxytocin receptor-knockout embryos transferred into wild-type surrogates had low survival rates during diapause. Our results indicate that oxytocin coordinates timing of embryonic development with uterine progression through pregnancy, providing an evolutionarily conserved mechanism for ensuring successful reproduction.