Faculty Bibliography

PURPOSE/OBJECTIVE:This study evaluated the safety and effectiveness of an intraoral light-emitting diode (LED)-based photobiomodulation (PBM) device to reduce the incidence and severity of oral mucositis (OM) from intensity modulated radiation therapy (IMRT) for head and neck cancer (HNC). METHODS:This randomized, double-blind, sham-controlled trial enrolled patients with HNC undergoing high-dose IMRT over 6-8 weeks, with or without concurrent chemotherapy. Participants received daily 10-min PBM or sham treatments immediately before IMRT sessions. Assessments were conducted at baseline, daily and weekly during IMRT, and two weeks post-IMRT. RESULTS:Eighty-five participants (42 PBM; 43 sham) were enrolled across 12 US sites. No device-related adverse events were observed, and 99.5% of initiated sessions were completed. In the intent-to-treat population, severe OM (WHO Grade ≥ 3) incidence was significantly lower with PBM across six weeks of IMRT (36.8% vs 57.1%; p = 0.046) and at two weeks post-treatment (10.8% vs 36.4%; p = 0.042). In the per-protocol population, the PBM arm reported significantly greater taste preservation (p = 0.034), lower increases in mouth/throat soreness (p = 0.029) and throat pain (p = 0.028) and needed fewer feeding tube placements (p = 0.073) than the control arm. CONCLUSION/CONCLUSIONS:Daily intraoral PBM therapy using an LED-based device was safe, well tolerated, and significantly reduced the incidence of severe OM and associated complications in HNC patients undergoing IMRT with or without concurrent chemotherapy. These findings align with guidelines recommending daily intraoral PBM therapy for preventing cancer therapy-related OM, a dose-limiting toxicity for which effective preventive interventions are needed. TRIAL REGISTRATION/BACKGROUND:Clinical Trials.gov Registration Number NCT03972527. Registered on June 3, 2019. Daily intraoral PBM therapy using an LED-based device was safe, well tolerated, and significantly reduced the incidence of severe OM and associated complications in HNC patients undergoing IMRT with or without concurrent chemotherapy. These findings align with guidelines recommending daily intraoral PBM therapy for preventing cancer therapy-related OM, a dose-limiting toxicity for which effective preventive interventions are needed.

OBJECTIVES/OBJECTIVE:To test whether unilateral recurrent laryngeal nerve (RLN) transection elicits side specific transcriptomic responses in rat vocal fold compartments. We compared the medial thyroarytenoid (MTA) muscle and mucosa on the left versus right, accounting for baseline laterality. METHODS:Unilateral RLN transection was performed in five adult rats (Left RLN: 2-males, 1-female; Right RLN: 1-male, 1-female). 5-weeks post-injury, the medial thyroarytenoid (MTA) muscle and vocal fold mucosa were harvested for RNA sequencing. Differential expression analysis compared Left-denervated versus Right-denervated tissues. A separate control Left-versus-Right analysis (1-male; 1-female) was used to assess baseline laterality and to contextualize TF transcription-factor inferences. TF activity was inferred using perturbation-based signatures, and baseline trends were used to classify overlapping signals as consistent with, opposite to, or distinct from baseline laterality. RESULTS:Left RLN denervation elicited distinct transcriptional responses in both compartments. In mucosa, TFs governing epithelial stability were reduced while regenerative cues were activated, suggesting impaired differentiation and recruitment of progenitor-like programs. In MTA, left-sided injury increased TFs consistent with stress signaling and mitochondrial compensation. TFs involved in epigenetic stability were reduced. Lateralized activity was observed in developmental regulators putatively related to positional memory or differential stress adaptation. Pathway analysis revealed enrichment of skeletal development processes in MTA and immune/matrix regulation in mucosa, indicating coordinated remodeling across muscle and epithelial compartments. CONCLUSION/CONCLUSIONS:RLN injury produces side-specific muscle and mucosal changes, with left-sided denervation showing stronger atrophy and stress responses. These results emphasize the importance of laterality and coordinated tissue adaptation. LEVEL OF EVIDENCE/METHODS:NA.

Stereotactic radiosurgery evolved from the desire to achieve highly precise and accurate target ablation using radiation energy. Over the past 3 decades, the range of indications for stereotactic radiosurgery has expanded significantly, making it a valuable treatment option-and often a first-line approach-for various intracranial conditions, including benign and malignant brain tumors, vascular malformations, and functional disorders. This narrative review offers a comprehensive, yet not exhaustive, overview of the current evidence, technical considerations, and areas of nuance and controversy regarding these indications and dose selection. It serves as a quick reference guide for neurosurgeons and radiation oncologists working in this field. In addition, tables are included that detail the indications, expected results, dose prescriptions, and anticipated outcomes, assisting clinicians in both clinical settings and procedural planning.

OBJECTIVE:To evaluate the feasibility of deep learning-based automated segmentation of the facial and vestibulocochlear nerves within the cisternal and intracanalicular segments on high-resolution magnetic resonance imaging. STUDY DESIGN AND SETTING/METHODS:This was a retrospective imaging study conducted at a tertiary referral center. PATIENTS/METHODS:Twenty-two adult patients with normal internal auditory canal magnetic resonance imaging and no skull base pathology were included. METHODS:Manual segmentation of the facial and vestibulocochlear nerves was performed on axial constructive interference in steady state magnetic resonance images using 3D Slicer. The dataset was divided into training, validation, and test subsets. A three-dimensional U-Net convolutional neural network was trained with standard augmentation. Additional Medical Open Network for Artificial Intelligence-based architectures, including Attention U-Net, Dynamic U-Net, and U-Net++, were trained and compared under identical preprocessing and training conditions. RESULTS:All models generated anatomically plausible segmentations on qualitative review. The baseline U-Net achieved a test Dice similarity coefficient of 0.6398. Dynamic U-Net demonstrated the highest validation performance (Dice = 0.6236), while U-Net++ achieved the highest test performance (Dice = 0.6716). Attention U-Net demonstrated lower performance in this small-structure segmentation task. Performance trends were consistent with the challenges inherent to segmenting thin neural structures with limited voxel representation. CONCLUSIONS:Deep learning-based segmentation of the facial and vestibulocochlear nerves on high-resolution magnetic resonance imaging is feasible within a limited retrospective dataset. Model selection appears important for small-structure segmentation, with Dynamic U-Net and U-Net++ demonstrating relatively higher performance trends within this limited dataset. Although performance metrics were modest and derived from a limited test dataset, automated segmentation showed consistent anatomic overlap with manual labels on qualitative review. These findings provide preliminary technical groundwork for future validation in larger cohorts and extension to clinically relevant applications such as cochlear nerve integrity in implant candidates.

Oral cancer is one of the most painful malignancies, with pain driven primarily by algogenic mediators in the tumor microenvironment, including nerve growth factor (NGF). Although NGF monoclonal antibodies alleviate cancer pain in patients, clinical development was halted because of adverse effects, highlighting the need for safer alternatives. Neuropilin-1 (NRP1), a nonenzymatic NGF coreceptor, mediates NGF and tropomyosin receptor kinase A (TrkA) signaling, yet its role in cancer pain is unknown. We found that NRP1 is robustly coexpressed with TrkA in peptidergic nociceptors of mouse trigeminal ganglia. NRP1 antagonists inhibited NGF-induced sensitization of transient receptor potential vanilloid 1 in isolated trigeminal nociceptors and reduced NGF-induced periorbital mechanical allodynia in mice. Conditioned medium from human tongue squamous carcinoma HSC-3 cells contained NGF and sensitized transient receptor potential vanilloid 1 in trigeminal nociceptors and induced periorbital mechanical allodynia. Immunoneutralization of NGF and NRP1 blockade inhibited these effects. Our results show that NRP1 is a necessary coreceptor for the pronociceptive effects of NGF/TrkA signaling in the trigeminal system and implicate NGF and NRP1 in oral cancer pain. Current oral cancer pain management strategies, including opioids, are inadequate and are burdened by unacceptable side effects. By abrogating the actions of growth factors, including NGF, NRP1-targeted therapies represent an alternative approach to mitigate cancer pain and possibly slow tumor growth.

Larry Young had a huge impact on the study of neuropeptides and social behavior. Here I give an autobiographical perspective on how Larry and his work influenced the field and my own career.

BackgroundPostoperative care following endoscopic sinus surgery (ESS) aims to optimize mucosal healing, reduce inflammation, and minimize infectious complications. Although saline irrigation is considered standard of care, the potential benefit of adding topical antibiotics, such as mupirocin, during the early postoperative period remains uncertain.ObjectiveTo evaluate whether short-term postoperative mupirocin nasal irrigation improves clinical, endoscopic, and microbiological outcomes compared with saline irrigation alone following ESS.MethodsThis prospective, randomized, double-blinded, placebo-controlled trial included adults with chronic rhinosinusitis undergoing ESS. Patients were randomized to receive either mupirocin (0.05%) nasal irrigation or placebo saline irrigation twice daily for 21 days postoperatively. Outcomes assessed within the first 3 months included patient-reported symptoms using the sinonasal outcomes test (SNOT-22) and visual analog scale (VAS), endoscopic findings (mucosal edema, polyp formation, crusting, granulation tissue, and purulence), postoperative sinus culture results, and need for systemic antibiotics.ResultsSixty-eight patients were enrolled, and 56 completed follow-up. Both groups demonstrated significant postoperative improvement in SNOT-22 and VAS scores compared with preoperative baseline, without significant between-group differences. However, the mupirocin group showed significantly lower rates of endoscopic mucosal edema and polyp formation at 1 month postoperatively. Negative postoperative cultures were also more frequent in the mupirocin group, with reduced need for systemic oral antibiotics. No significant differences were observed in crusting, granulation tissue, purulence, steroid use, or pain medication requirements.ConclusionShort-term prophylactic postoperative mupirocin nasal irrigation after ESS does not confer additional improvement in patient-reported quality-of-life outcomes compared with saline alone but appears to reduce early inflammatory endoscopic changes, bacterial culture positivity, and need for systemic antibiotics. Larger studies with longer follow-up are needed to confirm these findings.

BACKGROUND:Identifying oral potentially malignant disorders and oral cavity cancer early can lead to better patient outcomes. The guideline panel evaluated the usefulness of light-based adjuncts for screening adults without mucosal abnormalities and for determining the need for biopsy among adults with mucosal abnormalities in the oral cavity or on the lip. TYPES OF STUDIES REVIEWED/METHODS:The authors conducted a living systematic review to evaluate evidence on the benefits and harms of light-based adjuncts and a scoping review to assess people and clinician values and preferences regarding the use of light-based adjuncts and biopsy of mucosal abnormalities. The guideline panel used this evidence to formulate recommendations according to the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework. The framework also guided the panel's consideration of required resources, equity, acceptability, and feasibility in shaping the final recommendations. RESULTS:The guideline panel formulated 2 recommendations and 2 good practice statements. For adults with and without mucosal abnormalities, they formulated conditional recommendations against the use of light-based adjuncts on the basis of very low certainty evidence. The good practice statements urge clinicians to perform a clinical oral examination in all adult patients. CONCLUSIONS AND PRACTICAL IMPLICATIONS/CONCLUSIONS:Biopsy remains the reference standard for establishing a definitive diagnosis of an oral potentially malignant disorder and oral squamous cell carcinoma. All adults should undergo a clinical oral examination in primary care settings. When implementing or adapting these recommendations, local contexts should be considered to promote equitable access to early detection.

BACKGROUND:Early detection of oral potentially malignant disorders (OPMDs) and oral cavity cancer can improve patient prognosis. In this guideline, the authors address the use of vital staining, specifically toluidine blue, as an adjunct to screen adults without mucosal abnormalities and to determine the need for biopsy among adults with mucosal abnormalities in the oral cavity. TYPES OF STUDIES REVIEWED/METHODS:The authors conducted systematic searches to identify evidence on the benefits and harms of using vital staining as an adjunct as well as patient and clinician values and preferences regarding the use of this adjunct. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework to formulate recommendations. As part of the framework, the panel also considered the resources required, equity, acceptability, and feasibility when formulating recommendations. RESULTS:The panel formulated 2 recommendations and 2 good practice statements. For adults with and without mucosal abnormalities, the panel recommend against the use of vital staining as an adjunct (conditional recommendation, very low certainty). The good practice statements encourage clinicians to perform a clinical oral examination in all adult patients. CONCLUSIONS AND PRACTICAL IMPLICATIONS/CONCLUSIONS:Biopsy remains the first choice for obtaining a definitive diagnosis of an OPMD and oral squamous cell carcinoma. Clinical oral examination should be performed in all asymptomatic adults with no clinically evident mucosal abnormality. When implementing or adapting these recommendations, local contexts should be taken into account to ensure equitable access to early detection.