Faculty Bibliography

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.

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.

OBJECTIVE:What we hear may influence postural control, particularly in people with vestibular hypofunction. Would hearing a moving subway destabilize people similarly to seeing the train move? We investigated how people with unilateral vestibular hypofunction and healthy controls incorporated broadband and real-recorded sounds with visual load for balance in an immersive contextual scene. DESIGN/METHODS:Participants stood on foam placed on a force-platform, wore the HTC Vive headset, and observed an immersive subway environment. Each 60-second condition repeated twice: static or dynamic visual with no sound or static white noise or real recorded subway station sounds [real] played from headphones. SETTING/METHODS:Human motion laboratory. PARTICIPANTS/METHODS:41 healthy controls (mean age 52 years, range 22-78) and 28 participants with unilateral peripheral vestibular hypofunction (mean age 61.5, 27-82). MAIN OUTCOME MEASURES/METHODS:We collected center-of-pressure (COP, anterior-posterior, medio-lateral) from the force-platform and head (anterior-posterior, medio-lateral, pitch, yaw, roll) from the headset and quantified root mean square velocity (cm/s or rad/s). RESULTS:Adjusting for age, the vestibular group showed significantly more sway than controls on: COP medio-lateral (no sound or real with static or dynamic visual); COP anterior-posterior (only on dynamic visuals in the presence of either sound); head medio-lateral and anterior-posterior (all conditions), head pitch and yaw (only on dynamic visuals in the presence of either sound). A significant increase in sway with sounds was observed for the vestibular group only on dynamic visuals COP anterior-posterior and head yaw (real) and head anterior-posterior and pitch (either sound). CONCLUSIONS:The addition of auditory stimuli, particularly contextually-accurate sounds, to a challenging, standing balance task in real-life simulation increased sway in people with vestibular hypofunction but not in healthy controls. TRIAL REGISTRATION/BACKGROUND:Clinical trial registrationThis study was registered on clinicaltrials.gov at the following link: https://clinicaltrials.gov/study/NCT04479761.

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.

Gamma knife stereotactic radiosurgery is one of the most common procedures performed to manage patients with vestibular schwannoma. With a history that spans over 40 years, there has been continued evolution in radiosurgery technique and understanding of outcomes. The goal has always been to achieve long-term inactivation of tumor growth, commonly with tumor volumetric regression, and preservation of neurologic function. Challenges remain particularly pertaining to hearing preservation and other related symptoms such as those related to balance and tinnitus. Current discussions span a variety of topics including the importance of cochlear dose, the timing of the radiosurgery intervention as opposed to initial observation, the interpretation of imaging changes after radiosurgery, and the value of hearing augmentation strategies.

The current management of vestibular schwannomas (VS) includes observation, microsurgery, and stereotactic radiosurgery (SRS) or radiotherapy. Both microsurgery (MS) and irradiation have the potential for treatment failures. For microsurgical failures, options include observation, revision surgery, and SRS. SRS is most commonly used, as it carries a low risk of adverse events. Salvage MS following previous MS is reserved for specific cases and is often surgically challenging. For radiosurgical failures, both salvage MS and repeat SRS may be used. Salvage MS following SRS also tends to be challenging, although excellent facial nerve outcomes are achievable. Furthermore, repeat SRS is an emerging concept and should be considered in small tumors that are growing but are asymptomatic. This chapter is aimed at reviewing an approach to failure of primary interventions for vestibular schwannomas, with an emphasis on the time interval between modalities, tumor control rates, functional outcomes, and complications.

OBJECTIVES/OBJECTIVE:To investigate fall risk among older adults with bilateral sensorineural hearing loss (BHL) by comparing single task (ST) and dual task (DT) performance on the instrumented "Timed Up & Go" test (iTUG). The TUG is a well-validated clinical tool for fall risk; addition of wireless sensors increases the test's sensitivity and allows for subcomponent analysis. METHODS:Adults with audiometrically confirmed normal hearing or BHL were prospectively recruited and screened for visual, musculoskeletal, neurologic, or vestibular pathology and Dizziness Handicap Inventory (DHI) < 10. Total and sub-component iTUG data in the ST and DT condition (serial subtraction) was collected. RESULTS:35 adults (50-78 years) were included: 20 (mean 69 years) with BHL and 15 controls (mean age 63 years). Total iTUG duration did not differ between groups in either the ST or DT condition. In sit-to-stand, BHL were significantly slower than controls (p < 0.03) in both ST and DT conditions. In the final subcomponent (stand-to-sit), a significant interaction was observed such that the BHL group were significantly slower with DT compared to the control group. CONCLUSIONS:BHL performed slower on sub-component analysis of the iTUG compared with age-matched normal hearing controls. Slower times on the final iTUG phase for BHL may suggest a lower threshold for attentional capacity that may be cumulative. Further investigation into the impact of treatment (including amplification and training) is warranted.