Faculty Bibliography

BACKGROUND:Adrenal venous sampling is routinely used to lateralize aldosterone hypersecretion but has an unclear role in adrenocorticotropic hormone-independent autonomous hypercortisolism. We define clinical scenarios where adrenal venous sampling provides value for surgical decision-making. METHODS:We performed a single-center retrospective review of patients undergoing adrenal venous sampling for hypercortisolism (January 2012-April 2025). Lateralization was defined by a lateralization ratio >2 using aldosterone as a reference hormone. We also conducted a scoping review of studies describing adrenal venous sampling use in hypercortisolism identified through a comprehensive literature search. RESULTS:Nine patients with isolated hypercortisolism were included, of which 88.9% were female, with a median age of 60 years (range, 41-76). Seven patients presented with mild autonomous cortisol secretion and 2 with overt Cushing's syndrome. Six patients had bilateral adrenal nodules. Mean nodule size was 2.71 ± 0.85 cm. Eight patients underwent a 1-mg dexamethasone suppression test, with all patients meeting the >1.8 μg/dL threshold for elevated serum cortisol (mean dexamethasone suppression test cortisol: 7.13 ± 4.82 μg/dL). Adrenal venous sampling lateralization corresponded to the larger or unilateral nodule in 5 patients, was nonlateralizing in 3, and correctly lateralized to the smaller nodule in 1 patient with similarly sized lesions (1.9 cm versus 2.0 cm), enabling correct-side surgery and resolution of symptoms of overt Cushing's. Seven isolated hypercortisolism patients underwent adrenalectomy, all with benign pathology. Nine studies were included in the scoping review, demonstrating heterogeneous adrenal venous sampling lateralization criteria. CONCLUSION/CONCLUSIONS:Adrenal venous sampling may be useful in select patients with adrenocorticotropic hormone-independent hypercortisolism and similarly sized bilateral adrenal nodules in order to prevent incorrect-side adrenalectomy or unnecessary bilateral adrenalectomy.

OBJECTIVES/OBJECTIVE:To investigate whether active low-level laser therapy (LLLT) provides an incremental effect as an adjunct to a comprehensive voice therapy (VT) program, compared to VT combined with a placebo laser therapy (PLT), in women with dysphonia. METHODS:This prospective, parallel-group, triple-blind, placebo-controlled clinical trial enrolled 46 women (18-60 years), with 39 completing the 8-week per-protocol analysis (VT-LLLT n = 22; VT-PLT n = 17). The experimental group received infrared LLLT (808 nm, 100 mW, 30 J) prior to VT, while the control group received a placebo laser. The primary outcome was the auditory-perceptual overall severity (OS) of dysphonia. Secondary outcomes included acoustic measures, vocal self-assessment, and laryngeal videostroboscopic parameters. RESULTS:Both groups demonstrated significant pre-to-post improvements across auditory-perceptual, self-assessment, and acoustic parameters, with no statistically significant Group × Time interaction for the primary outcome (OS) or any secondary functional variable. Conversely, laryngeal imaging evaluated via Generalized Linear Models (GLM) revealed a statistically significant Group × Time interaction for the recovery of the vocal fold edge contour (P = 0.005), indicating a localized morphological improvement in the VT-LLLT group. No adverse events were associated with the interventions. CONCLUSION/CONCLUSIONS:Although adjunctive active LLLT significantly accelerates the localized macroscopic restoration of the vocal fold edge contour, this structural change does not translate into superior functional, acoustic, or perceptual voice outcomes compared to placebo. Behavioral VT unequivocally remains the primary and dominant therapeutic driver for functional vocal recovery in women with dysphonia.

OBJECTIVES/UNASSIGNED:Cerebellopontine angle (CPA) tumors, including vestibular schwannomas (VS), often require microsurgical resection. These are typically surgical procedures performed by co-surgeons, and some controversy and confusion exist regarding use of common procedural terminology (CPT) codes for billing, given the American Medical Association (AMA) describes two distinct coding sets for such cases. This investigation endeavored to: (1) Comprehensively review all surgical coding options; (2) instruct on application; and (3) explore contemporary coding trends among surgeons. DESIGN/UNASSIGNED:A multi-disciplinary task force (otologist/neurotologists and neurosurgeons) performed direct correspondence with various surgical societies, private consultancies, and the AMA. Survey instruments were distributed to active surgeons. SETTING/UNASSIGNED:Investigational period: 2022 to 2025. Survey instruments distributed at the 2023 American Neurotology Society (ANS) Fall Meeting. PARTICIPANTS/UNASSIGNED:ANS, American Academy of Otolaryngology (AAO-HNSF), and the North American Skull Base Society (NASBS) representatives. OUTCOMES MEASURES/UNASSIGNED:Usage rate for CPT code sets (percentage of responders). RESULTS/UNASSIGNED:Two CPT coding systems are currently accepted for surgical management of CPA tumors. The traditional/legacy codes (Indicator-2) allow use of co-surgery modifiers (-62). The newer approach/resection codes (skull base codes; Indicator-1) restrict modifier use. The history, application, and controversies surrounding the codes are detailed herein. About 40% of surgeons reported use of the traditional codes, while 45 to 49% use the skull base codes. Response rate was 31% of the active ANS membership in 2023. CONCLUSION/UNASSIGNED:The AMA recognizes two CPT code sets for surgical management of CPA tumors. Both are appropriate, if properly applied. Contemporary surgeons likely utilize the sets in equal proportions.

OBJECTIVES/OBJECTIVE:Recurrent respiratory papillomatosis (RRP), caused by chronic HPV-6/11 infection, leads to repeated papilloma growth requiring frequent surgical removal. DNA immunotherapy INO-3107 aims to induce HPV antigen-specific T-cell responses and reduce surgical burden. This analysis evaluated HPV-specific immune responses after INO-3107 and their association with long-term clinical outcomes. METHODS:Adults with HPV-6/11-associated RRP received INO-3107 in a Phase 1/2 trial and were followed for one year, with additional clinical follow-up in a long-term extension. Number of surgeries in Years 1 and 2 was compared with the pre-treatment year. Blood and laryngotracheal tissue collected at Day 0 and Year 1 were analyzed for treatment-related changes in T-cell activity. Safety was assessed throughout. RESULTS:Thirty-two patients were treated; 28 continued into Year 2. At Year 1, most evaluable patients showed increased T-cell activity: 73% (19/26) demonstrated persistent expanded T-cell populations in blood, 71% (12/17) showed higher T-cell clone counts in laryngotracheal tissue, indicating site-specific immune infiltration. Antiviral T-cell signatures were enriched in 88% for CD4+ Th1 and CD8+ cytotoxic, and 71% for CD8+ effector memory, suggesting durable proinflammatory and memory responses in airway tissue. Mean annual surgeries decreased over time in the overall population (Baseline: 4.1, Year 1: 1.7, Year 2: 0.9). Similar durable reductions were observed in Responder subgroups. INO-3107 was well-tolerated, with no treatment-related serious adverse events. CONCLUSION/CONCLUSIONS:INO-3107 generates increased HPV-directed T-cell responses and substantially reduced surgical procedures over two years, supporting its ability to provide long-term clinical benefit in RRP without requiring additional surgeries during the dosing window.

Oral cancer patients suffer pain that is patient-specific and heterogeneous at the site of the tumor. Protease-activated receptor 2 (PAR₂), a G-protein coupled receptor and an oral cancer mediator, is activated by protease cleavage of an N-terminal ligand. Once cleaved, the receptor is retained at the plasma membrane or re-distributed (trafficking) to internal sites followed by downstream protease-specific signaling. The oral cancer tumor microenvironment (TME) is replete with protases that activate PAR₂, potentially evoking PAR₂ trafficking and signaling that is unique to each cancer and reflecting the protease composition of the individual TMEs. To measure PAR₂ cleavage activity in oral cancer samples, an array of overlapping peptides spanning the PAR₂ N-terminus was assembled. In this feasibility study, we assayed the cleavage activity of individual PAR₂-activating proteases and mixtures of proteases modeling the oral cancer TME. Additionally, we confirmed that PAR₂-cleaving proteases are active in oral cancer patient saliva, a sample that can be collected non-invasively to measure PAR₂ cleavage in patients when they are experiencing pain prior to surgery. Further studies should elucidate the utility of the peptide array to measure PAR₂-activating proteolysis in cancer samples.

BACKGROUND:Major breakthroughs in the clinical application of liquid biopsies, such as the use of salivary samples to detect biomarkers for the early detection of diseases and conditions, are on the horizon. Historically, late detection of oral cancer has contributed to high morbidity and mortality, making scientific advancements in this field particularly impactful. This guideline evaluates and provides recommendations for commercially available salivary adjunct tests in the United States designed specifically for screening adults without mucosal abnormalities and for determining the need for biopsy among adults with mucosal abnormalities of the oral cavity or lip. TYPES OF STUDIES REVIEWED/METHODS:The researchers used living systematic review methodology to identify evidence on the benefits and harms of salivary adjunct tests. They also conducted a scoping review of patient and clinician values and preferences regarding the use of these adjuncts and evaluated data on other contextual factors, including costs, equity, acceptability, and feasibility of these tests. The guideline panel formulated a recommendation after applying the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework. RESULTS:The panel issued 2 research-only recommendations, limiting the use of salivary adjunct tests for early oral cancer detection to research settings: 1 for adults with oral mucosal or lip abnormalities, and 1 for adults without mucosal abnormalities. Three good practice statements were also formulated: 2 recommending the performance of clinical oral examinations for all adult patients, and 1 recommending biopsy or referral for adult patients with persistent oral mucosal abnormalities. PRACTICAL IMPLICATIONS/CONCLUSIONS:All adult patients should receive a clinical oral examination. When a mucosal abnormality is identified, biopsy remains the reference standard for establishing a definitive diagnosis. Salivary diagnostic adjuncts, whether used to screen asymptomatic adults or to determine the need for biopsy in adults with mucosal abnormalities, should not be used in regular clinical practice or as a public health screening measure outside of a research setting. Further research is needed to establish the potential role of salivary adjunct tests in clinical practice.

Cochlear implants (CIs) stimulate auditory neurons with electric pulse trains whose amplitudes are modulated using envelopes extracted from different frequency bands, conveying essential speech cues. This study investigated how the rate of stimulation pulses affects envelope processing and speech perception in ten post-lingually deaf CI users. Amplitude modulation (AM) detection and consonant identification were examined using acoustic stimuli processed by multi-channel and single-channel strategies, with pulse rates ranging from 125 to 2000 pulses per second (pps) for multi-channel stimulation and from 125 to 4000pps for single-channel stimulation. The single-channel conditions encoded the overall broad-band speech envelope by a single electrode and were used to isolate within-electrode temporal modulation coding. For AM detection, the modulation frequency was 25 Hz ensuring sufficient modulation sampling across all carrier rates tested. Even at 125pps, the 25-Hz modulation was represented by five pulses per modulation cycle. Results revealed a significant decline in both AM detection and consonant identification at 125pps, suggesting that poorer speech recognition at low rates may be partly attributable to limitations in temporal modulation processing rather than solely to a restricted range of representable envelope frequencies. Consonant recognition performance remained stable across clinically relevant pulse rates (250-2000pps), though significant listener- and feature-specific effects were observed. Notably, while AM detection and consonant recognition were not significantly correlated within this small cohort, significant correlations were found between single-channel and multi-channel performance in both tasks. These findings support an important role for within-electrode temporal coding in CI speech perception and highlight the clinical relevance of individual variability in pulse rate effects.

Diagnostic adjuncts for oral potentially malignant disorders such as leukoplakia or erythroplakia can aid the clinician in triaging abnormal lesions and facilitate both biopsy site selection and surgical management. No adjuncts replace gold standard biopsy and histopathological examination, and their optimal use requires training and experience. This article covers the potential applications, both in primary and expert settings, of adjuncts, such as tissue autofluorescence, toluidine blues staining, and cytopathology. It covers new and emerging adjuncts such as confocal microscopy, liquid biopsy, oral microbiome testing, and the role of artificial intelligence. Incisional biopsy site selection and techniques will also be discussed.

The locus coeruleus (LC) brainstem cell group is evolutionarily conserved across vertebrates and influences both mind (cognition) and body (cardiorespiratory, metabolic, and immune functions) via two-putatively distinct-spontaneous activity patterns. Yet, the degree to which spontaneous LC firing rates and patterns are homogeneous across species has never been assessed due to inherently limited sample sizes. To remedy this, we pooled cross-species data from 20 laboratories to show that firing rates differ across species and are modulated by sex, age, and type of in vitro or in vivo preparation. Contrary to the prevailing dual-mode firing pattern schema, we observed patterns spread across a low-dimensional manifold, with subregions enriched for specific biological factors and neurodegenerative disease models. Our findings show considerable diversity in an ancestral vertebrate neuromodulatory system.

BACKGROUND:Evaluation of otolaryngology resident technical performance has historically relied on subjective perioperative feedback. Despite various assessment tools attempting to provide consistent surgical skill evaluations, current methods remain inherently subjective. AIM/OBJECTIVE:This proof-of-concept pilot study aimed to assess if a 3-dimensional surgical navigation system could capture objective surgical data during endoscopic sinus surgery (ESS). A secondary aim was to analyze if there were any differences between novice and practiced trainees. METHODS:Navigation System. Prior to the surgery, surgical landmarks were defined with sensory beacons in the navigation system using the patient's preoperative computed tomography (CT) scan. Metrics included time to reach beacons, number of alerts at each beacon, and instrument speed. RESULTS: < .001). IMPACT/CONCLUSIONS:This study demonstrates the feasibility of collecting objective, navigation-based intraoperative metrics during live surgery and is a first step toward building a comprehensive objective assessment tool in ESS. We hope this report encourages further research into this technology's application in objective resident skill assessment and correlation with concurrent faculty assessments.