Faculty Bibliography

Hearing loss is a highly prevalent disease state affecting almost 1 in 5 individuals globally. Growing research shows that untreated or undertreated hearing loss carries significant long-term sequelae, including increased risk of social isolation, depression, and cognitive decline, among other ramifications. Limited awareness and common misperceptions among the general US adult population and primary care providers contribute to low rates of referral to hearing specialty clinics and underutilization of hearing aids, cochlear implants, and other rehabilitative devices. Comprised of diverse membership, the Hearing Health Collaborative (HHC) was formed in May 2021 to identify and overcome challenges impacting good health care practices and public policy on hearing care in connection with healthy aging. This editorial documents a recent outcome of the HHC derived from a structured A3 process. Specifically, initiative 2, a proposal to develop a simple, clinically anchored staging system primarily for use by frontline providers and patients, is presented. Unlike other common disorders that harbor long-term health sequelae, a corresponding pragmatic clinical staging system-leveraging precedent disease staging convention, based on clinically meaningful outcomes and prognosis for acquired hearing loss-does not exist. The development of this staging system will potentially allow for improved communication across providers and patients, facilitate referral pathways, and ultimately enable patient access to timely and appropriate care.

OBJECTIVE:To characterize patient outcomes after primary stereotactic radiosurgery (SRS) for the management of sporadic facial nerve schwannoma. STUDY DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Six tertiary referral centers across the United States and United Kingdom. PATIENTS/METHODS:Adults undergoing SRS from 2000 through 2023 for sporadic facial nerve schwannoma along any segment of the facial nerve were included. Patients with NF2-related schwannomatosis were excluded. INTERVENTION/METHODS:Stereotactic radiosurgery. MAIN OUTCOME MEASURE/METHODS:Long-term tumor control. RESULTS:Among 60 patients meeting inclusion, the median age at SRS was 52 years (IQR: 41 to 64) with a median tumor size of 19.5 mm (IQR: 14.7 to 22.8). Tumors commonly involved the internal auditory canal (73%), cisternal (49%), geniculate/labyrinthine (47%), and tympanic segments (22%). Two patients experienced SRS failure and underwent salvage treatment; salvage-free survival rates (95% CI; number still at risk) at 1, 3, 5, and 10 years after SRS were 100% (100 to 100; 55), 100% (100 to 100; 36), 100% (100 to 100; 18), and 87% (72 to 100; 9), respectively. Among 31 (52%) patients with House-Brackmann (HB) grade I facial function at presentation, only 6 demonstrated worse facial function at a median of 3.2 years (IQR: 1.7 to 6.6) after SRS. Of 18 patients with serviceable hearing (AAO-HNS class A/B) at SRS, 13 maintained serviceable hearing at a median of 1.0 years (IQR: 0.5 to 4.9) of post-SRS audiometric follow-up. CONCLUSIONS:Durable tumor control after primary SRS for sporadic facial nerve schwannoma is achieved in most patients. Among those with HB grade I facial function at presentation, treatment with SRS harbors limited additional risk of facial paresis beyond observation alone.

OBJECTIVE:NF2-related schwannomatosis (NF2-SWN) is an autosomal dominant genetic disorder characterized by the development of schwannomas, meningiomas, and spinal ependymomas. Treatment with bevacizumab, a monoclonal antibody against VEGF, has been shown to result in decreased vestibular schwannoma size and hearing improvement in ~50% of NF2-SWN patients. It is unknown whether the same degree of benefit is seen in younger patients compared with older patients. The objective of this study is to determine the association between age and bevacizumab treatment outcomes in NF2-SWN. STUDY DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Tertiary referral center. PATIENTS/METHODS:Thirty-seven patients with NF2-SWN. INTERVENTIONS/METHODS:Bevacizumab. MAIN OUTCOME MEASURES/METHODS:Change in tumor size of 20% or more. RESULTS:This study includes 37 patients with NF2-SWN who were treated with bevacizumab at our institution between 2014 and 2024. They were divided into 2 groups: 22 adults over the age of 25 (26 to 71 y) and 15 adolescent and young adult (AYA) patients under the age of 25 (12 to 24 y). The median treatment duration was 2.1 years. A significantly higher proportion of AYA schwannomas (37.5%, n=9) exhibited radiographic tumor progression during the treatment period compared with those of the older patient group (11.9%, n=5) (P=0.026), despite similar pre-treatment growth rates. There was no significant difference in the proportion of older and younger patients with hearing decline, improvement, or stability (P>0.05). CONCLUSIONS:AYA patients were significantly more likely to exhibit progression of tumor growth during bevacizumab treatment compared with older patients, though no significant differences were detected in hearing outcomes.

INTRODUCTION/UNASSIGNED:Skull base surgery is a highly innovative, multidisciplinary field that brings together teams of neurosurgeons, otolaryngology-head and neck surgeons (OHNS), plastic surgeons, ophthalmologists, radiation oncologists, and others. However, not long ago, the nascent field was instead characterized by isolated individual brilliance. METHODS/UNASSIGNED:This paper explores the contributions of several key players toward breaking silos and transforming the field into what it is today. Our analysis centers on the formation of the North American Skull Base Society (NASBS), and the instrumental role that it played in the development of skull base surgery. We interviewed 12 past presidents of the NASBS and 2 prominent figures in skull base surgery. The contents of those 20 hours and 38 minutes of interviews and documents from initial NASBS meetings were analyzed. Key moments were segmented into short video clips, which complement this manuscript and are available on the NASBS website. RESULTS/UNASSIGNED:A compelling narrative of collaboration, mentorship, and tenacity emerged from our analysis. In the 20th century, the field of skull base surgery was characterized mainly by courageous but isolated efforts by neurosurgeons and OHNS surgeons. Through mentorship, collaboration, and incredible innovation, it has since grown into a multidisciplinary, cutting-edge specialty that utilizes the strengths of several medical specialties. This transformation was largely facilitated by the formation of the NASBS in 1989, which enabled worldwide communication and collaboration among those dedicated to advancing the field. CONCLUSION/UNASSIGNED:The growth of skull base surgery in North America and the instrumental role of the NASBS highlight the power of collaboration and innovation. It is important to recognize and celebrate the key players who facilitated the creation and success of the NASBS, which continues to unite young members across countless disciplines under one banner.

Developing populations of connected neurons often share spatial and/or temporal features that anticipate their assembly. A unifying spatiotemporal motif might link sensory, central, and motor populations that comprise an entire circuit. In the sensorimotor reflex circuit that stabilizes vertebrate gaze, central and motor partners are paired in time (birthdate) and space (dorso-ventral). To determine if birthdate and/or dorso-ventral organization could align the entire circuit, we measured the spatial and temporal development of the sensory circuit node: the vestibular ganglion neurons. We discovered that progressive dorsal-to-ventral organization closely predicts vestibular ganglion development, with additional organization along its functional (rostrocaudal) axis. With an acute optical lesion and calcium imaging paradigm, we found that this common temporal axis anticipated functional sensory-to-central partner matching. We propose a "first-come, first-served" model in which birthdate organizes and assembles the sensory, central, and motor populations that comprise the gaze stabilization circuit, a general strategy for poly-synaptic circuit assembly across embryonically-diverse neural populations.

OBJECTIVE:With regulatory approval of HPV-specific immunotherapy for recurrent respiratory papillomatosis (RRP) and growing experience with systemic bevacizumab, a management algorithm incorporating these medical treatments is warranted. DATA SOURCES AND METHODS/METHODS:RRP Foundation (RRPF) Key Opinion Leaders offer a proposed management algorithm for adults with RRP considering published literature and commercial drug availability. RESULTS:Preventative HPV vaccination should be considered for all patients. Determination of HPV type and pulmonary imaging are important for contemporary RRP patient care and assist in decision making. Risks and benefits of papilloma debulking as needed versus medical management of RRP must be deliberated on a patient case-by-case basis. HPV-specific immunotherapy that induces an HPV-specific T cell response to target the underlying HPV infection that is the cause of RRP is safe, offers the possibility of durable disease control following a short treatment course and is the recommended first-line medical treatment for patients who wish to avoid the risks of repeat procedural management. Papilloma disease control with systemic bevacizumab, which carries defined risks and must be continued for clinical benefit is the recommended second-line medical treatment for patients who do not achieve a complete response with immunotherapy and wish to continue medical management. For patients who elect to be treated with debulking procedures as needed, use of locally-administered adjuvant should be considered. CONCLUSION/CONCLUSIONS:This proposed management algorithm from the RRPF serves as a contemporary resource and information guide for adult patients with RRP and their physicians considering treatment options.

OBJECTIVES/OBJECTIVE:Traditionally, disorders of the vocal fold (VF) mucosa and underlying musculature have been regarded as mutually exclusive entities. However, emerging evidence from other organ systems suggests mucosal and muscle compartments engage in reciprocal interactions with functional consequences. We hypothesized that similar crosstalk exists in the VF, whereby fibrotic mucosa influences adjacent muscle. To model this process, we stimulated human VF fibroblasts (HVOX) with TGF-β1, a central mediator of fibrosis, and examined the effects on rat VF myoblasts (rVF-Mbs), as well as reciprocal influences of rVF-Mbs on fibroblasts. METHODS:HVOX fibroblasts were stimulated with 10 ng/mL TGF-β1, and the effects on rVF-Mbs were assessed using conditioned media and co-culture. Myotube formation was evaluated by immunofluorescence, and nuclear localization of Smad2/3 was examined in conditioned media experiments. qRT-PCR quantified transcripts related to myogenic differentiation and Smad2/3 signaling. ALK4/5 inhibition was performed in co-culture to test TGF-β/Smad2/3-signaling pathway involvement. Reciprocal effects were examined by changes in fibrogenic gene expression in HVOX fibroblasts. RESULTS:Both conditioned media and co-culture suppressed myogenic differentiation in rVF-Mbs; increased inhibition was observed in co-culture, as indicated by reduced myotube formation, decreased Myh2 expression, and activation of Smad2/3 signaling. ALK4/5 inhibition abrogated these effects. Differentiating rVF-Mbs attenuated the fibrogenic phenotype of HVOX fibroblasts. CONCLUSIONS:Fibrotic VF mucosal cells can impair myogenic differentiation through TGF-β/Smad2/3-mediated fibroblast-myoblast crosstalk, and myogenic cells may exert reciprocal anti-fibrotic effects. These findings suggest mucosa-muscle interactions may contribute to VF pathology and highlight Smad2/3 as a potential therapeutic target. LEVEL OF EVIDENCE/METHODS:NA STUDY DESIGN: In vitro.

Despite extensive research on hemispheric asymmetries, the mechanisms regulating lateralized brain functions are incompletely understood. Growing evidence suggests that lateralized neural circuits are side-specifically controlled, in part, by neuropeptides acting as neuromodulators, paracrine factors, and neurohormones. This review highlights evidence supporting this concept in the contexts of lateralized pain processing in the amygdala, control of auditory signaling, lateralized interoceptive signaling, and side-specific endocrine regulation. Our focus is primarily on rodent studies, with supporting data from humans and nonmammalian species, including turtles and nematodes. Left-right side-specific control may be rooted in a bipartite, lateralized organization of neuropeptide systems. Neuropeptides with asymmetric actions may act locally within specific brain regions or be coordinated across the neuraxis. These findings converge on a model in which neuropeptides enable lateralized control through interconnected mechanisms spanning gene expression, neural circuits, and behavioral outcomes.