Faculty Bibliography

The endoscopic transsphenoidal approach (ETSA) is a commonly used technique that allows for the minimally invasive removal of sellar and parasellar lesions. Augmented reality (AR) applications in ETSA are hypothesized to enhance intraoperative visualization by integrating a 3D-reconstructed model into the operative field. This study describes the workflow and surgical outcomes associated with the Endoscopic Surgical Navigation Advanced Platform (EndoSNAP, Surgical Theater, Cleveland, OH, USA), an AR platform designed for surgical planning and intraoperative navigation in ETSA for sellar and parasellar lesions. We analyzed a cohort of patients who underwent ETSA tumor resection using EndoSNAP. Preoperative MRI and CT scans were reconstructed and merged into a single 360° AR model using the Surgical Rehearsal Platform software. The model was then imported into EndoSNAP, which was integrated with the endoscope and neuronavigation system for real-time intraoperative use. Patient demographics, tumor characteristics, extent of resection (EOR), and endocrinologic and neurologic outcomes were recorded. Eighteen adult patients with newly diagnosed (83%) and recurrent (17%) tumors were included. Pathologies consisted of pituitary adenoma (72%), craniopharyngioma (11%), meningioma (11%), and chordoma (6%). Optic compression was present in 56% of patients, with preoperative visual deficits in 70% of them. Cavernous sinus invasion was observed in 17% of tumors. Preoperative hormonal excess and insufficiency were noted in 56% and 28% of cases, respectively. The mean preoperative tumor volume was 21.4 ± 17 cm³, which decreased to 0.4 ± 0.3 cm³ postoperatively. The mean EOR was 93.6 ± 3.6%. Postoperative complications included CSF leaks requiring surgical repair (17%), seizures related to pre-existing hemispheric trauma (6%), pulmonary embolism (6%), deep venous thrombosis (6%), and sinusitis (6%). These findings suggest that AR-enhanced visualization through EndoSNAP is a feasible and potentially beneficial adjunct in ETSA for sellar and parasellar tumor resection.

We often exert greater cognitive resources (i.e., listening effort) to understand speech under challenging acoustic conditions. This mechanism can be overwhelmed in those with hearing loss, resulting in cognitive fatigue in adults and potentially impeding language acquisition in children. However, the neural mechanisms that support listening effort are uncertain. Evidence from human studies suggests that the cingulate cortex is engaged under difficult listening conditions and may exert top-down modulation of the auditory cortex (AC). Here, we asked whether the gerbil cingulate cortex (Cg) sends anatomical projections to the AC that facilitate perceptual performance. To model challenging listening conditions, we used a sound discrimination task in which stimulus parameters were presented in either "Easy" or "Hard" blocks (i.e., long or short stimulus duration, respectively). Gerbils achieved statistically identical psychometric performance in Easy and Hard blocks. Anatomical tracing experiments revealed a strong, descending projection from layer 2/3 of the Cg1 subregion of the cingulate cortex to superficial and deep layers of the primary and dorsal AC. To determine whether Cg improves task performance under challenging conditions, we bilaterally infused muscimol to inactivate Cg1 and found that psychometric thresholds were degraded for only Hard blocks. To test whether the Cg-to-AC projection facilitates task performance, we chemogenetically inactivated these inputs and found that performance was only degraded during Hard blocks. Taken together, the results reveal a descending cortical pathway that facilitates perceptual performance during challenging listening conditions.

The pro-fibrotic effects of glucocorticoids may lead to a suboptimal therapeutic response for vocal fold (VF) pathology. Targeting macrophage-fibroblast interactions is an interesting therapeutic strategy; macrophages alter their phenotype to mediate both inflammation and fibrosis. In the current study, we investigated concentration-dependent effects of methylprednisolone on the fibrotic response, with an emphasis on YAP/TAZ-TEAD signaling, and inflammatory gene expression in VF fibroblasts in physical contact with macrophages. We sought to provide foundational data to optimize therapeutic strategies for millions of patients with voice/laryngeal disease-related disability. Following induction of inflammatory (M(IFN/LPS)) and fibrotic (M(TGF)) phenotypes, THP-1-derived macrophages were seeded onto HVOX vocal fold fibroblasts. Cells were co-cultured ± 0.3-3000 nM methylprednisolone ± 3 µM verteporfin, a YAP/TAZ inhibitor. Inflammatory (CXCL10, TNF, PTGS2) and fibrotic genes (ACTA2, CCN2, COL1A1) in fibroblasts were analyzed by real-time polymerase chain reaction after cell sorting. Ser211-phosphorylated glucocorticoid receptor (S211-pGR) was assessed by Western blotting. Nuclear localization of S211-pGR and YAP/TAZ was analyzed by immunocytochemistry. Methylprednisolone decreased TNF and PTGS2 in fibroblasts co-cultured with M(IFN/LPS) macrophages and increased ACTA2 and CCN2 in fibroblasts co-cultured with M(IFN/LPS) and M(TGF). Lower concentrations were required to decrease TNF and PTGS2 expression and to increase S211-pGR than to increase ACTA2 and CCN2 expression and nuclear localization of S211-pGR. Methylprednisolone also increased YAP/TAZ nuclear localization. Verteporfin attenuated upregulation of CCN2, but not PTGS2 downregulation. High concentration methylprednisolone induced nuclear localization of S211-pGR and upregulated fibrotic genes mediated by YAP/TAZ activation.

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.

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.

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.

Oral cavity cancer is associated with high morbidity and mortality, particularly with advanced stage diagnosis. Oral cavity cancer, typically squamous cell carcinoma (OSCC), is often preceded by oral potentially malignant disorders (OPMDs), which comprise eleven disorders with variable risks for malignant transformation. While OPMDs are clinical diagnoses, conventional oral exam followed by biopsy and histopathological analysis is the gold standard for diagnosis of OSCC. There is vast heterogeneity in the clinical presentation of OPMDs, with possible visual similarities to early-stage OSCC or even to various benign oral mucosal abnormalities. The diagnostic challenge of OSCC/OPMDs is compounded in the non-specialist or primary care setting. There has been significant research interest in technology to assist in the diagnosis of OSCC/OPMDs. Artificial intelligence (AI), which enables machine performance of human tasks, has already shown promise in several domains of medical diagnostics. Computer vision, the field of AI dedicated to the analysis of visual data, has over the past decade been applied to clinical photographs for the diagnosis of OSCC/OPMDs. Various methodological concerns and limitations may be encountered in the literature on OSCC/OPMD image analysis. This narrative review delineates the current landscape of AI clinical photograph analysis in the diagnosis of OSCC/OPMDs and navigates the limitations, methodological issues, and clinical workflow implications of this field, providing context for future research considerations.

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.

INTRODUCTION/UNASSIGNED:Patients with oral cancer often experience intense functional pain due to mechanical stimulation at the cancer site. The role of mechanosensitive ion channels in oral cancer pain, such as TRPV4, is not fully understood. OBJECTIVES/UNASSIGNED:Our objective was to investigate the role of Schwann cell TRPV4 in oral cancer pain. METHODS/UNASSIGNED:imaging, and patch-clamp electrophysiology. The effect of TRPV4 activation on Schwann cell responses to mechanical stimulation was evaluated using a piezo stimulator. Conditioned media (CM) from TRPV4-activated Schwann cells were injected into the mouse paw to evaluate the contribution of TRPV4 in Schwann cells to mechanical hypersensitivity. RESULTS/UNASSIGNED:responses and whole-cell membrane currents in human Schwann cells. Mechanoactivated currents in human Schwann cells were inhibited by the TRPV4 antagonist HC-067047. Schwann cell CM induced mechanical hypersensitivity in mice, which was blocked by pre-treatment with HC-067047. CONCLUSION/UNASSIGNED:TRPV4 activation plays a role in mediating mechanically induced pain of oral cancer.