Faculty Bibliography

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.

BACKGROUND:Management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) when cisplatin is contraindicated is controversial. We aimed to assess whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab. METHODS:weekly beginning week 1 of radiotherapy (eight cycles), with intensity-modulated radiotherapy (70 Gy in 35 fractions over 7 weeks). Stratification factors were tumour and nodal stage, ECOG performance status and comorbidity, and primary site and p16 status. The phase 2 primary endpoint was progression-free survival in the intention-to-treat population. There was one prespecified interim futility analysis at 50% of progression-free survival information. If the observed hazard ratio was 1·0 or more, favouring cetuximab, early stopping would be considered. Extended follow-up analysis was post hoc. This trial is registered with ClinicalTrials.gov, NCT03258554, and is closed to enrolment. FINDINGS/RESULTS:Following a ten-patient safety lead-in, the phase 2 trial enrolled 190 patients from March 12, 2019, to July 30, 2021, 186 of whom were randomly assigned (123 to durvalumab and 63 to cetuximab). Median age was 72 years (IQR 64-77), 30 (16%) patients were women and 156 (84%) were men. Phase 2 accrual was suspended in July 30, 2021, following an interim futility analysis, and permanently closed in Sept 1, 2022. The phase 3 part of the trial was not conducted. At a median follow-up of 2·3 years (IQR 1·9-3·1) for the extended follow-up (data cutoff July 31, 2023; post-hoc analysis), 2-year progression-free survival was 50·6% (95% CI 41·5-59·8) in the durvalumab group versus 63·7% (51·3-76·1) in the cetuximab group (hazard ratio 1·33 [95% CI 0·84-2·12]; p=0·89). Adverse events were similar in both groups. The most common grade 3-4 adverse events were dysphagia (26 [22%] of 119 patients in the durvalumab group vs 18 [30%] of 61 patients in the cetuximab group), lymphopenia (33 [28%] vs 20 [33%]), and oral mucositis (13 [11%] vs 11 [18%]). Four (3%) patients in the durvalumab group and one (2%) in the cetuximab group died from treatment-related adverse events (death not otherwise specified, laryngeal oedema, lung infection, and respiratory failure in the durvalumab group and sudden death not otherwise specified in the cetuximab group). INTERPRETATION/CONCLUSIONS:Our findings suggest that durvalumab did not improve outcomes compared with cetuximab in patients with HNSCC with contraindications to cisplatin. Further trials are needed to define the standard of care for this population. FUNDING/BACKGROUND:US National Cancer Institute and AstraZeneca.

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.

Nerve growth factor (NGF) monoclonal antibodies inhibit chronic pain, yet failed to gain approval due to worsened joint damage in osteoarthritis patients. We report that neuropilin-1 (NRP1) is a coreceptor for NGF and tropomyosin-related kinase A (TrkA) pain signaling. NRP1 was coexpressed with TrkA in human and mouse nociceptors. NRP1 inhibitors suppressed NGF-stimulated excitation of human and mouse nociceptors and NGF-evoked nociception in mice. NRP1 knockdown inhibited NGF/TrkA signaling, whereas NRP1 overexpression enhanced signaling. NGF bound NRP1 with high affinity and interacted with and chaperoned TrkA from the biosynthetic pathway to the plasma membrane and endosomes, enhancing TrkA signaling. Molecular modeling suggested that the C-terminal R/KXXR/K NGF motif interacts with the extracellular "b" NRP1 domain within a plasma membrane NGF/TrkA/NRP1 of 2:2:2 stoichiometry. G α interacting protein C-terminus 1 (GIPC1), which scaffolds NRP1 and TrkA to myosin VI, colocalized in nociceptors with NRP1/TrkA. GIPC1 knockdown abrogated NGF-evoked excitation of nociceptors and pain-like behavior. Thus, NRP1 is a nociceptor-enriched coreceptor that facilitates NGF/TrkA pain signaling. NRP binds NGF and chaperones TrkA to the plasma membrane and signaling endosomes via the GIPC1 adaptor. NRP1 and GIPC1 antagonism in nociceptors offers a long-awaited nonopioid alternative to systemic antibody NGF sequestration for the treatment of chronic pain.

Sensorimotor reflex circuits engage distinct neuronal subtypes, defined by precise connectivity, to transform sensation into compensatory behavior. Whether and how motor neuron populations specify the subtype fate and/or sensory connectivity of their pre-motor partners remains controversial. Here, we discovered that motor neurons are dispensable for proper connectivity in the vestibular reflex circuit that stabilizes gaze. We first measured activity following vestibular sensation in pre-motor projection neurons after constitutive loss of their extraocular motor neuron partners. We observed normal responses and topography indicative of unchanged functional connectivity between sensory neurons and projection neurons. Next, we show that projection neurons remain anatomically and molecularly poised to connect appropriately with their downstream partners. Lastly, we show that the transcriptional signatures that typify projection neurons develop independently of motor partners. Our findings comprehensively overturn a long-standing model: that connectivity in the circuit for gaze stabilization is retrogradely determined by motor partner-derived signals. By defining the contribution of motor neurons to specification of an archetypal sensorimotor circuit, our work speaks to comparable processes in the spinal cord and advances our understanding of principles of neural development.

Although cochlear implants (CI) successfully replace the sense of hearing, they do not restore natural hearing. Still, CI users adapt to this novel signal, reaching meaningful levels of speech recognition in clinical tests that focus on repetition of words and short sentences. However, many patients who score above average in clinical speech perception tests complain that everyday speech interactions are both difficult and cognitively draining. In part this difficulty may be due to the naturally rapid pace of everyday discourse. We report a study in which 12 CI users aged 23 to 77, recalled multi-sentence discourse presented without interruption, or in the condition of interest, when passages were paused at major linguistic boundaries, with participants given control of when to initiate the next segment. Comprehension of the discourse structure was based on a formalized representational system that organizes discourse elements hierarchically to index the relative importance of different elements to the overall understanding of the discourse. Results showed (a) better recall when CI users were allowed to control the discourse pace, (b) an overall effect of aging, with older CI users recalling discourse less accurately, (c) better recall for passages with higher average inter-word predictability, (d) a "semantic hierarchy effect" reflected by better recall of main ideas versus minor details, (e) an attenuation of the semantic hierarchy effect for low predictability passages. Results underscore the benefits of extra processing time in addressing CI listening challenges and highlight the limited ecological validity of single-word or single-sentence speech recognition tests.

The sensation of gravity anchors our perception of the environment and is important for navigation. However, the neural circuits that transform gravity into commands for navigation are undefined. We first determined that larval zebrafish (Danio rerio) navigate vertically by maintaining a consistent heading across a series of upward climb or downward dive bouts. Gravity-blind mutant fish swim with more variable heading and excessive veering, leading to less effective vertical navigation. After targeted photoablation of ascending vestibular neurons and spinal projecting midbrain neurons, but not vestibulospinal neurons, vertical navigation was impaired. These data define a sensorimotor circuit that uses evolutionarily conserved brainstem architecture to transform gravitational signals into persistent heading for vertical navigation. The work lays a foundation to understand how vestibular inputs allow animals to move effectively through their environment.