Faculty Bibliography

Alston's singing mouse has emerged as an intriguing model for the comparative study of vocal control. New work on the species sets the stage to understand the proximate mechanisms and evolutionary roots of novel acoustic communication traits.

BACKGROUND:Oral cavity cancer represents a public health challenge in Latin America and the Caribbean (LAC), where exposure to modifiable risk factors such as tobacco and alcohol remains high and inequalities in access to health services contribute to delayed diagnosis and poor outcomes. This study aimed to develop consensus-based recommendations to strengthen the prevention and early detection of oral cavity cancer and oral potentially malignant disorders in LAC. METHODS:A multi-phase study using a Delphi approach was conducted. An initial qualitative survey with regional experts identified barriers, facilitators, and priority actions for oral cavity cancer prevention and early detection. Preliminary recommendations were refined through feasibility assessment by international advisors and subsequently evaluated in a quantitative Delphi round using a Likert scale. RESULTS:Twenty-four experts from 12 LAC countries participated in the Delphi process, including research investigators, clinicians, and health service managers. The panel had a mean age of 49.4 (SD 10.3) years and included 41.7 % women. Seven recommendations achieved consensus, addressing key domains of oral cavity cancer control including primary prevention interventions, screening of high-risk individuals, establishment of structured referral pathways, improved surveillance systems, and expansion of access to diagnostic services in underserved populations. High levels of agreement were observed across all recommendations. CONCLUSIONS:These consensus-based recommendations provide a regionally informed framework to guide oral cavity cancer prevention and early detection strategies in LAC. Strengthening coordinated actions across the continuum of care, including primary prevention, screening, referral, and diagnostic capacity, may contribute to reducing diagnostic delays and improving outcomes in the region.

Oral potentially malignant disorders (OPMDs) such as leukoplakia and erythroplakia may harbor dysplasia or progress to oral squamous cell carcinoma (OSCC), yet visual inspection alone is unreliable for risk assessment. Cytology offers a minimally invasive adjunct, but conventional approaches depend on manual feature extraction and subjective review. Herein we report a deep learning (DL) object detection model that directly classifies four cell phenotypes: differentiated squamous epithelial (DSE) cells, small round (SR) cells, leukocytes, and lone nuclei. The DL model produced cytology-derived parameters that correlated strongly with histopathologic diagnoses across 692 subjects with OPMDs, OSCC, and healthy controls, including declining DSE cell proportion and increasing SR cells and leukocytes with disease severity (p < 0.0001). The oral cancer numerical index (OCNI) achieved AUROC values up to 0.99 for malignant versus healthy lesions, with excellent reliability (intra-class correlation coefficient ≥ 0.96). This reproducible, minimally invasive test provides a robust platform for early detection and surveillance of OPMDs.

Peritoneal cavity fluid and mesothelial surfaces host distinct resident macrophage populations, among which include the well-described Gata6⁺ large cavity macrophages (LCMs) in peritoneal fluid. Here, we reveal that LCMs arise from two separable differentiation pathways. In the quantitatively minor pathway, monocytes gave rise to LYVE1⁺ LCMs but few Gata6⁺ LCMs. This pathway did not require the transcription factor Gata6 but was severely impaired in mice bearing three mutations in the -165 kb Zeb2 enhancer (Zeb2

PURPOSE/UNASSIGNED:To determine whether nasal intramucosal 5-fluorouracil (5-FU) injection improves outcomes after external dacryocystorhinostomy (DCR) in pediatric patients with nasolacrimal duct obstruction (NLDO). METHODS/UNASSIGNED:Multi-center retrospective non-comparative case series review of all DCR cases with intra-operative 5- FU injection performed between 2014 and 2023 on all patients age < 18 years. Each case was reviewed to determine if the patients had epiphora recurrence following surgery with 5-FU injection. RESULTS/UNASSIGNED:Sixteen pediatric patients with NLDO (19 eyes) underwent DCR and nasal intramucosal injections of 5-FU intra-operatively. One had a lost stent. Ten (53%) eyes were in patients with craniofacial syndromes. In all patients with the use of 5-FU there was no recurrence of tearing. Eight of the patients (42%) had already had at least one or two failed stents prior in which recurrence had occurred. There were no post-operative complications. CONCLUSION/UNASSIGNED:Adjuvant intramucosal 5-FU demonstrated a 100% success rate of epiphora not recurring following pediatric DCR without any complications in this small sample size, particularly in patients with increased risk of recurrence.

BACKGROUND/UNASSIGNED:Mal de débarquement syndrome (MdDS) is a chronic vestibular disorder of non-spinning vertigo, with various somatic, cognitive, and affective symptoms. The manifestation of MdDS is often only subjective, and different symptoms are variably emphasized when patients appraise the severity of their illness. The etiology of MdDS remains unclear but may lie in improperly sustained neuroplasticity in the velocity storage mechanism of the central vestibular system. Two broad approaches targeting velocity storage-one focusing on correcting velocity storage's maladapted behavior and the other on attenuating its contribution to higher-order processing-have yielded varying degrees of treatment success. METHODS/UNASSIGNED:We conducted a secondary analysis of data from our recent study contrasting the outcomes of the above two approaches. We examined the variations in individual emphases of separate symptoms by correlating the subjective ratings of overall MdDS severity with those of specific symptoms across time points for each subject. We also explored the possibility that variations in symptom presentation influence the responsiveness to the two approaches of treatment. RESULTS/UNASSIGNED:Many symptoms correlated with the overall severity rating, but even those that showed strong correlation among many subjects, such as dizziness, fatigue, and brain fog, were endorsed variably across subjects. A moderate unfavorable dependence on visual sensitivity was found for the responsiveness to the velocity storage attenuation treatment, which distinguished the two treatment approaches. CONCLUSION/UNASSIGNED:Results provide a glimpse into the complexity of MdDS manifestations. Individual variations in what contributes to their perceived overall symptom severity may aid the choice of treatment approach.

BACKGROUND:Preclinical evidence suggests statins enhance antitumor immunity. This study evaluates whether concurrent statin use during immune checkpoint inhibitor (ICI) therapy is associated with overall survival (OS) in mucosal head and neck squamous cell carcinoma (HNSCC). METHODS:This retrospective study uses Epic COSMOS, a multi-health system electronic health record dataset. Adults with mucosal HNSCC receiving PD-1 inhibitors were included. Concurrent statin use required ≥ 2 statin orders from -365 to +180 days relative to ICI initiation. The primary outcome was OS from ICI initiation to death or last encounter. RESULTS:Among 21 456 patients, 5719 (26.7%) met concurrent statin criteria. In the fully adjusted model, statin use was associated with increased mortality (HR 1.08; 95% CI 1.04-1.13). In drug-specific analysis, rosuvastatin was associated with reduced mortality (HR 0.87; 0.80-0.96). CONCLUSIONS:Class-level statin use was not associated with improved survival, likely reflecting confounding by cardiovascular comorbidity. Rosuvastatin-specific findings warrant prospective investigation.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Concurrent chemoradiotherapy (CCRT) is an effective treatment for various head and neck cancers; however, CCRT can result in significant swallowing impairment, presumably due largely to dysfunction of the muscles of swallowing, which are within the field of radiation. This translational study examines the mechanisms underlying CCRT-induced muscle dysfunction using (1) a rat model of CCRT and (2) analysis of archival human specimens. METHODS:131 Sprague Dawley rats were divided into experimental and control groups. Experimental rats received cisplatin and 5-fluorouracil intravenously, followed by 7 Gray radiation daily for 5 days. Rats were further split into three time points: acute (2 weeks), intermediate (5 months), and long-term (10 months), at which time tissue was harvested for analysis. Human samples included preexisting CCRT-treated and age- and sex-matched control muscle samples from head and neck cancer patients. Quantitative analyses of Paired Box Homeotic Gene 7-positive cells (Pax7 in rats; PAX7 in humans), fibrosis, muscle fiber size, and neuromuscular junctions were conducted and compared between groups in both rats and humans. RESULTS:Analysis demonstrated a significant decline in the percent of Pax7/PAX7-positive cells (a marker of muscle stem cells) after CCRT in both rats and humans, increased collagen percent, and decreased muscle percent in rats at 10 months. CCRT was associated with significantly reduced muscle fiber size in human specimens. Neuromuscular junction presence and morphology in rats were not affected. CONCLUSION/CONCLUSIONS:This translational study demonstrates significant alterations in head and neck muscles in both a rat model and human specimens from subjects exposed to CCRT. LEVEL OF EVIDENCE/METHODS:NA.

BACKGROUND/UNASSIGNED:Advances in endoscopic endonasal approaches in ventral skull base surgery have led to increasingly complex resections and reconstructions. This study investigates differences in postoperative outcomes, including postoperative cerebrospinal fluid (CSF) leak and infection, following anterior skull base surgery and reconstruction, as a function of the type of nasal packing (absorbable vs. nonabsorbable) used to bolster the skull base reconstruction. METHODS/UNASSIGNED:A retrospective chart review was performed at a single tertiary care institution. Patients who underwent ventral skull base surgery with placement of nasal packing between January 1, 2020, and December 1, 2023, were included. We included only patients of a single rhinologist (S.L.) involved. Outcome measures included postoperative CSF leaks and postoperative infection. RESULTS/UNASSIGNED: = 0.309) between these two cohorts of patients. CONCLUSION/UNASSIGNED:While no significant differences were found in the rate of postoperative CSF leak or infection, additional patient factors should be taken into consideration when choosing between absorbable and nonabsorbable nasal packing for ventral skull base reconstruction. LEVEL OF EVIDENCE/UNASSIGNED:4.

OBJECTIVE:Pediatric tracheostomy emergencies are high-acuity events requiring rapid, coordinated team-based care. This study assessed objective team performance and used in situ simulation to identify systems factors, including latent safety threats (LSTs) and resilience supports, that influence pediatric tracheostomy emergency readiness across diverse clinical settings. METHODS:In situ simulations of pediatric tracheostomy emergencies (obstructed or partially dislodged tubes) were conducted across inpatient floors, critical care units, and emergency departments at 11 pediatric hospitals. Time to completion of critical actions was recorded using the NeoCHART+™ for PEAK-II mobile application. Structured debriefs identified LSTs and resilience supports at unit and hospital levels. Multivariable Cox proportional hazards models assessed predictors of time-critical actions (tube replacement, suction, first effective ventilation) and the percentage of critical actions completed. RESULTS:Sixty-seven baseline simulations were conducted across 11 institutions. Seventy-seven percent of teams replaced an identical tracheostomy tube within 5 minutes (median 188.4 seconds, [IQR 165.3, 204.6]). Teams reported a median of 3.2 LSTs per simulation (IQR 3.0, 4.0). Common LSTs included attempted ventilation through occluded tracheostomy tubes, unclear leadership, ambiguous role definitions, and non-standardized equipment locations. Teams with a RT and at institutions with a dedicated tracheostomy team performed time-critical actions faster. DISCUSSION/CONCLUSIONS:In situ simulation revealed LSTs, resilience supports, and performance variability that may influence effective pediatric tracheostomy emergency response at the systems level. IMPLICATIONS FOR PRACTICE/CONCLUSIONS:Variability identified in systems factors and team performance can guide targeted interventions to improve pediatric tracheostomy emergency preparedness.