Faculty Bibliography

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.

BACKGROUND:Post-tonsillectomy hemorrhage (PTH) is a highly studied outcome of tonsillectomy with serious consequences. Various treatments and interventions have been utilized to decrease post-tonsillectomy hemorrhage. The off-label use of tranexamic acid (TXA) is of growing interest to control PTH but has not been incorporated in management guidelines. This scoping review plans to summarize existing studies from the scientific literature on the use of tranexamic acid for post-tonsillectomy hemorrhage. METHODS/UNASSIGNED:We used the Preferred Reporting Items for Systematic Reviews or Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR). The review will cover studies including patients undergoing tonsillectomy who were treated with TXA in the peri-operative or post-operative period. We include randomized controlled trials, retrospective, prospective, and case series. A database-specific search strategy will be used to search records across. Two reviewers will independently screen and extract data. Tables and visual representations will be utilized to present the extracted data. REGISTRATION DETAILS/UNASSIGNED:The protocol will be registered in Open Science Framework and published in PLOS One.

Communication between intracellular organelles including lysosomes and mitochondria has recently been shown to regulate cellular proliferation and fitness. The way lysosomes and mitochondria communicate with each other (lysosomal/mitochondrial interaction, LMI) is, emerging as a major determinant of tumor proliferation and growth. About 30% of squamous carcinomas (including squamous cell carcinoma of the head and neck, SCCHN) overexpress TMEM16A, a calcium-activated chloride channel, which promotes cellular growth and negatively correlates with patient survival. We have recently shown that TMEM16A drives lysosomal biogenesis, but its impact on mitochondrial function has not been explored. Here, we show that in the context of high TMEM16A SCCHN, (1) patients display increased mitochondrial content, specifically complex I; (2) In vitro and in vivo models uniquely depend on mitochondrial complex I activity for growth and survival; (3) NRF2 signaling is a critical linchpin that drives mitochondrial function, and (4) mitochondrial complex I and lysosomal function are codependent for proliferation. Taken together, our data demonstrate that coordinated lysosomal and mitochondrial activity and biogenesis via LMI drive tumor proliferation and facilitates a functional interaction between lysosomal and mitochondrial networks. Therefore, inhibition of LMI instauration may serve as a therapeutic strategy for patients with SCCHN. Implications: Intervention of lysosome-mitochondria interaction may serve as a therapeutic approach for patients with high TMEM16A expressing SCCHN.

In nature, animal vocalizations can provide crucial information about identity, including kinship and hierarchy. However, lab-based vocal behavior is typically studied during brief interactions between animals with no prior social relationship, and under environmental conditions with limited ethological relevance. Here, we address this gap by establishing long-term acoustic recordings from Mongolian gerbil families, a core social group that uses an array of sonic and ultrasonic vocalizations. Three separate gerbil families were transferred to an enlarged environment and continuous 20-day audio recordings were obtained. Using a variational autoencoder (VAE) to quantify 583,237 vocalizations, we show that gerbils exhibit a more elaborate vocal repertoire than has been previously reported and that vocal repertoire usage differs significantly by family. By performing gaussian mixture model clustering on the VAE latent space, we show that families preferentially use characteristic sets of vocal clusters and that these usage preferences remain stable over weeks. Furthermore, gerbils displayed family-specific transitions between vocal clusters. Since gerbils live naturally as extended families in complex underground burrows that are adjacent to other families, these results suggest the presence of a vocal dialect which could be exploited by animals to represent kinship. These findings position the Mongolian gerbil as a compelling animal model to study the neural basis of vocal communication and demonstrates the potential for using unsupervised machine learning with uninterrupted acoustic recordings to gain insights into naturalistic animal behavior.

BACKGROUND:Accurate intraoperative diagnosis is crucial for differentiating between primary CNS lymphoma (PCNSL) and other CNS entities, guiding surgical decision-making, but represents significant challenges due to overlapping histomorphological features, time constraints, and differing treatment strategies. We combined stimulated Raman histology (SRH) with deep learning to address this challenge. METHODS:We imaged unprocessed, label-free tissue samples intraoperatively using a portable Raman scattering microscope, generating virtual H&E-like images within less than three minutes. We developed a deep learning pipeline called RapidLymphoma based on a self-supervised learning strategy to (1) detect PCNSL, (2) differentiate from other CNS entities, and (3) test the diagnostic performance in a prospective international multicenter cohort and two additional independent test cohorts. We trained on 54,000 SRH patch images sourced from surgical resections and stereotactic-guided biopsies, including various CNS neoplastic/non-neoplastic lesions. Training and test data were collected from four tertiary international medical centers. The final histopathological diagnosis served as ground-truth. RESULTS:In the prospective test cohort of PCNSL and non-PCNSL entities (n=160), RapidLymphoma achieved an overall balanced accuracy of 97.81% ±0.91, non-inferior to frozen section analysis in detecting PCNSL (100% vs. 77.77%). The additional test cohorts (n=420, n=59) reached balanced accuracy rates of 95.44% ±0.74 and 95.57% ±2.47 in differentiating IDH-wildtype diffuse gliomas and various brain metastasis from PCNSL. Visual heatmaps revealed RapidLymphoma's capabilities to detect class-specific histomorphological key features. CONCLUSIONS:RapidLymphoma proves reliable and valid for intraoperative PCNSL detection and differentiation from other CNS entities. It provides visual feedback within three minutes, enabling fast clinical decision-making and subsequent treatment strategy planning.

BACKGROUND:Oral cancer causes intense pain at the primary site, and such pain can impair oral functions. However, the underlying mechanisms for oral cancer pain are still not fully understood. In the present study, it is investigated whether programmed cell death protein 1 (PD-1) is involved in the development of oral cancer pain. METHODS:RMP1-14, a specific anti-PD-1 antibody, was injected into spinal trigeminal nucleus caudalis (Sp5C) and measured pain behaviors using von Frey filaments and dolognawmeter. Western blotting and immunofluorescence staining were performed to analyze the expression of PD-1 and tumor necrosis factor alpha (TNFα) in the Sp5C. RESULTS:It was observed that the PD-1 antibody significantly inhibited mechanical hypersensitivity and functional allodynia in our oral cancer pain mouse model. Moreover, we found that TNFα was highly upregulated in the Sp5C following the induction of oral cancer pain and that intra-Sp5C injection of the PD-1 antibody diminished the upregulation of TNFα. It was found that genetic deletion of TNFα or its receptor antagonism synergized the analgesic effect of PD-1 antibody on oral cancer pain. CONCLUSION/CONCLUSIONS:Our results suggest that PD-1 in the Sp5C contributes to oral cancer pain by altering TNFα signaling in the trigeminal nociceptive system, and PD-1 could be targeted to develop a novel approach for oral cancer pain management.

OBJECTIVE:To compare cochlear implant (CI) speech perception outcomes in patients with sporadic vestibular schwannoma (VS) managed with observation, radiosurgery, or microsurgery. STUDY DESIGN/METHODS:Retrospective review. SETTING/METHODS:Eleven tertiary academic medical centers. PATIENTS/METHODS:One hundred patients with sporadic VS who received an ipsilateral CI. INTERVENTIONS/METHODS:Ipsilateral cochlear implantation. MAIN OUTCOME MEASURES/METHODS:Pure-tone thresholds, monosyllabic speech perception testing scores, and rates of open-set speech acquisition. RESULTS:Of the 100 patients studied, 54 underwent microsurgery, 26 underwent radiosurgery, 19 continued observation, and 1 underwent multimodal therapy. Among all patients, the median post-implantation pure-tone average was 31 dB (interquartile range [IQR] 25-39 dB) and the median monosyllabic speech perception score was 30% (IQR 0-60%) at a median of 12 months (IQR 5-25 months) post-implantation. Patients who were managed with microsurgery (median speech perception score 11%, IQR 0-52%) exhibited poorer implant outcomes overall compared with those managed with observation (median speech perception score 52%, IQR 40-72%) or radiosurgery (median speech perception score 30%, IQR 16-60%). Open-set speech perception was achieved in 61% of patients managed with microsurgery, 100% with observation, and 80% with radiosurgery. In a multivariable setting, those managed with observation (p = 0.02) or who underwent radiosurgery (p = 0.04) were significantly more likely to achieve open-set speech perception compared with patients who underwent microsurgery. CONCLUSIONS:Cochlear implants offer benefit in selected patients with sporadic VS. Although achieved in over half of people after microsurgery, open-set speech perception is more reliably attained in patients who are treated with observation or radiosurgery compared with microsurgical resection. These data may inform patient counseling and VS tumor management in people who may benefit from implantation.

AIM/UNASSIGNED:This case highlights the rarely reported complication of facial paresis following buccal fat pad removal and its management. BACKGROUND/UNASSIGNED:The buccal fat pad is a vital structure in facial aesthetics. In recent years, buccal fat pad removal for mid facial sculpting has gained popularity among patients owing in part to the rise of social media in plastic surgery. Although buccal fat pad removal is usually a safe procedure, potential complications can be quite severe, and can include infection, over-resection, asymmetry, hematoma, facial nerve or parotid duct injury and trismus. CASE DESCRIPTION/UNASSIGNED:Herein we describe a case of iatrogenic left facial paresis secondary to buccal fat removal, and discuss the importance of appropriate patient counseling, meticulous technique, and post-operative care in the event of a complication. CONCLUSION/UNASSIGNED:High dose corticosteroids and facial therapy can be effective in treating iatrogenic facial palsy secondary to buccal fat pad removal. CLINICAL SIGNIFICANCE/UNASSIGNED:Although buccal fat pad removal has become a common procedure for midface sculpting, the risks remain serious and patient counseling regarding possible complications, including transient facial palsy, is paramount. Meticulous technique as well as knowledge of the relationships between the buccal fat pad, the parotid duct, and the buccal branches of the facial nerve are vital in the prevention of facial paresis when removing buccal fat.

OBJECTIVE:To investigate whether a new preoperative education and discharge planning protocol reduced unexpected discharge delays for patients undergoing reconstructive surgery for head and neck cancer. METHODS:A quality improvement (QI) intervention was implemented in January 2021 with several components to address historically prolonged observed lengths of stay (LOS) with head and neck cancer patients. The intervention added a preoperative educational visit with a head and neck cancer advanced practice provider, a standardized preoperative speech and swallow assessment, a personalized patient care plan document, discussion of inpatient hospital stay expectations, and early discharge planning. The intervention group included patients who underwent the preoperative education protocol from February to December 2021. For comparison, an age and sex-matched control group was constructed from inpatients who had been admitted for similar procedures in the 2 years prior to the QI intervention (2019-2020) and received standard of care counseling. RESULTS:Our study demonstrated a significant reduction in observed to expected LOS ratio after implementation of the intervention (1.24 ± 0.74 control, 0.95 ± 0.52 intervention; P = .012). DISCUSSION/CONCLUSIONS:We discuss a preoperative education QI intervention at our institution. Our findings demonstrate that our intervention was associated with decreased LOS for patients undergoing head and neck reconstructive surgeries. IMPLICATIONS FOR PRACTICE/CONCLUSIONS:This QI study shows the benefit of a new standardized preoperative education and discharge planning protocol for patients undergoing head and neck reconstructive surgeries.

OBJECTIVE:Assess the use of video otoscopy (VO) as a tool for teaching Emergency Department (ED) residents and remote Otolaryngology consultation. STUDY DESIGN/METHODS:Survey and retrospective chart review. SETTING/METHODS:Tertiary care center. METHODS:Emergency Medicine resident physicians completed an otologic skill self-assessment and pathology followed by an interactive training on VO and postintervention assessment after 9 months of use. Outcomes compared change in pre- to posttraining scores. ED consultations using VO during this time period were reviewed to detect differences between the presumed diagnosis/treatment based only on phone consultation and VO image compared to the final diagnosis/treatment after in-person Otolaryngology consultation. RESULTS:Forty-six (63.1%) ED residents participated. Diagnostic accuracy improved by 20.7% overall. The most improved diagnoses were of a normal ear canal (+75%), tympanosclerosis (+58.4%), and ear canal foreign body (+57.1%); most challenging were external auditory canal cyst (-13.6%), hemotympanum (-11.3%), and cerumen (-1.9%). Cholesteatoma did not improve because all responses were incorrect; neither did tympanic membrane perforation because all were correct. Confidence in the otologic exam and anatomy also increased (P < .01). Thirteen consults used VO and 3 (23.1%) had a change in diagnosis/treatment after in-person Otolaryngology evaluation. CONCLUSION/CONCLUSIONS:Training on the use of VO significantly improves the confidence and diagnostic skills of ED providers for many pathologies. This application suggests the efficacy of an otologic e-consultation model.