Faculty Bibliography

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.

OBJECTIVES/OBJECTIVE:To assess a decade of experience of treating patients with high hearing risk cerebellopontine angle (CPA) epidermoid lesions and examine factors influencing postoperative outcomes, particularly hearing preservation. STUDY DESIGN/METHODS:Retrospective chart review. SETTING/METHODS:Single tertiary-referral center. PATIENTS/METHODS:Adults with CPA epidermoid lesions who presented with hearing loss or evidence of lesion involving vestibulocochlear nerve. INTERVENTIONS/METHODS:The studied intervention was microsurgical resection. MAIN OUTCOME MEASURES/METHODS:Main outcome measures included extent of resection, hearing preservation rate for patients with postoperative audiograms, and disease progression. RESULTS:Twenty-three adults with an average tumor volume of 15.63 ± 16.2 cm3 were included. Five lesions (22%) involved the full internal auditory canal (IAC), 11 (48%) had partial involvement, and 5 (22%) were IAC sparing. Most patients with IAC involvement (88%) had circumferential invasion of the canal. Patients underwent either a retrosigmoid (18, 79%) or combined retrolabyrinthine transpetrosal approach (5, 22%), and gross total resection was achieved in most cases (13, 57%). Of 12 patients with postoperative audiograms, 10 (83%) had preoperative hearing preserved. There was no statistically significant change in hearing scores with treatment based on preoperative extent of IAC involvement. Ten patients (43%) had residual lesions postoperatively, and 6 exhibited progression. One patient ultimately required reoperation 6 years after initial surgery. CONCLUSIONS:Preoperative hearing was preserved in the majority of the patients who underwent resection of CPA epidermoids via a retrosigmoid or transpetrosal approach. CPA epidermoids often invaded the IAC; however, degree of invasion was not associated with hearing outcomes.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Hydrocephalus after Gamma Knife® stereotactic radiosurgery (SRS) for vestibular schwannomas is a rare but manageable occurrence. Most series report post-SRS communicating hydrocephalus in about 1% of patients, thought to be related to a release of proteinaceous substances into the cerebrospinal fluid. While larger tumor size and older patient age have been associated with post-SRS hydrocephalus, the influence of baseline ventricular anatomy on hydrocephalus risk remains poorly defined. METHODS:A single-institution retrospective cohort study examining patients who developed symptomatic communicating hydrocephalus after undergoing Gamma Knife® SRS for unilateral vestibular schwannomas from 2011 to 2021 was performed. Patients with prior hydrocephalus and cerebrospinal fluid diversion or prior surgical resection were excluded. Baseline tumor volume, third ventricle width, and Evans Index (EI)-maximum width of the frontal horns of the lateral ventricles/maximum internal diameter of the skull-were measured on axial postcontrast T1-weighted magnetic resonance imaging. RESULTS:A total of 378 patients met the inclusion criteria; 14 patients (3.7%) developed symptomatic communicating hydrocephalus and 10 patients (2.6%) underwent shunt placement and 4 patients (1.1%) were observed with milder symptoms. The median age of patients who developed hydrocephalus was 69 years (IQR, 67-72) and for patients younger than age 65 years, the risk was 1%. For tumor volumes <1 cm3, the risk of requiring shunting was 1.2%. The odds of developing symptomatic hydrocephalus were 5.0 and 7.7 times higher in association with a baseline EI > 0.28 (P = .024) and tumor volume >3 cm3 (P = .007), respectively, in multivariate analysis. Fourth ventricle distortion on pre-SRS imaging was significantly associated with hydrocephalus incidence (P < .001). CONCLUSION/CONCLUSIONS:Patients with vestibular schwannoma with higher baseline EI, larger tumor volumes, and fourth ventricle deformation are at increased odds of developing post-SRS hydrocephalus. These patients should be counseled regarding risk of hydrocephalus and carefully monitored after SRS.

PURPOSE/OBJECTIVE:To investigate how adults with unilateral vestibular hypofunction and healthy controls incorporate visual and auditory cues for postural control in an abstract visual environment. METHODS:] components in low [0, 0.25 Hz], mid [0.25, 0.5 Hz] and high [0.5, 1 Hz] frequencies in the anterior-posterior direction. We used linear mixed-effects models to compares healthy controls (n = 41, mean age 52 years, range 22-78) to participants with unilateral peripheral vestibular hypofunction (n = 28, 61.5, 27-82), adjusting for age. RESULTS:Variance and low PSD: we observed a significant vestibular by visual load interaction in the presence of sounds, such that the vestibular group had significantly higher sway than controls only on dynamic visuals in the presence of sounds. Mid PSD: the vestibular group had significantly higher sway than controls regardless of condition. High PSD: the vestibular group had significantly higher sway than controls, except for the presence of sounds on static visuals. CONCLUSIONS:Patients with vestibular hypofunction used sounds to reduce sway in a static abstract environment and were somewhat destabilized by it in a dynamic environment. This suggests that sounds, when played from headphones, may function as an auditory anchor under certain level of challenge and specific tasks regardless of whether it's stationary or moving. Our results support that increased sway in middle frequencies reflects vestibular dysfunction.

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.