Optogenetics is a transformative technology based on light-sensitive microbial proteins, known as opsins, that enable precise modulation of neuronal activity with pulsed radiant energy. Optogenetics has been proposed as a means to improve auditory implant outcomes by reducing channel interaction and increasing electrode density, but the introduction of opsins into cochlear spiral ganglion neurons (SGNs) in vivo has been challenging. Here we test opsin delivery using a synthetically developed ancestral adeno-associated virus (AAV) vector called Anc80L65. Wild-type C57BL/6 mouse pups were injected via the round window of cochlea with Anc80L65 carrying opsin Chronos under the control of a CAG promoter. Following an incubation of 6-22 weeks, pulsed blue light was delivered to cochlear SGNs via a cochleosotomy approach and flexible optical fiber. Optically evoked auditory brainstem responses (oABRs) and multiunit activity in inferior colliculus (IC) were observed. Post-experiment cochlear histology demonstrated opsin expression in SGNs (mean = 74%), with an even distribution of opsin along the cochlear basal/apical gradient. This study is the first to describe robust SGN transduction, opsin expression, and optically evoked auditory electrophysiology in neonatal mice. Ultimately, this work may provide the basis for a new generation of cochlear implant based on light.

Objective The radiologic evaluation of patients with hearing loss includes computed tomography and magnetic resonance imaging (MRI) to highlight temporal bone and cochlear nerve anatomy. The central auditory pathways are often not studied for routine clinical evaluation. Diffusion tensor imaging (DTI) is an emerging MRI-based modality that can reveal microstructural changes in white matter. In this systematic review, we summarize the value of DTI in the detection of structural changes of the central auditory pathways in patients with sensorineural hearing loss. Data Sources PubMed, Embase, and Cochrane. Review Methods We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement checklist for study design. All studies that included at least 1 sensorineural hearing loss patient with DTI outcome data were included. Results After inclusion and exclusion criteria were met, 20 articles were analyzed. Patients with bilateral hearing loss comprised 60.8% of all subjects. Patients with unilateral or progressive hearing loss and tinnitus made up the remaining studies. The auditory cortex and inferior colliculus (IC) were the most commonly studied regions using DTI, and most cases were found to have changes in diffusion metrics, such as fractional anisotropy, compared to normal hearing controls. Detectable changes in other auditory regions were reported, but there was a higher degree of variability. Conclusion White matter changes based on DTI metrics can be seen in patients with sensorineural hearing loss, but studies are few in number with modest sample sizes. Further standardization of DTI using a prospective study design with larger sample sizes is needed.

Objectives To compare local recurrence-free survival (LRFS) in early oral cavity cancer (OCC) patients with positive/close frozen section (FS) cleared with further resection (R1 to R0) or positive FS not cleared (R1) to those with negative margins on initial FS analysis (R0). Data Sources PubMed, EMBASE, and Cochrane. Review Methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) for reporting in our study. Only English-language articles that included patients with OCC and local recurrence (LR) comparisons between R0 and initially R1 to final R0 or final R1 groups were included. We requested the raw data from the corresponding authors of eligible studies and performed an individual participant data (IPD) meta-analysis of LRFS outcomes across groups. Results Pooled LRFS data from 8 studies showed that patients in the R1 to R0 group had worse LRFS compared to the R0 group (hazard ratio [HR] = 2.897, P < .001). Patients in the R1 group were also found to have worse LRFS compared to the R0 group (HR = 3.795, P < .001). When compared to final R1 group, the initially R1 to final R0 only showed a trend toward better LRFS. Conclusion Margin revision of initially positive margins to “clear” based on FS guidance does not equate to an initially negative margin and does not significantly improve local control. These findings call into question the effectiveness of the current methodology of intraoperative FS in OCC resections and call for a prospective study to determine what system of resected specimen analysis best predicts completeness of resection.

Ultrasound is useful in the evaluation of oral tongue malignancies. More experience is needed to determine if it is reliable in determining preoperative DOI in light of the role this tumor parameter plays in the eighth edition of the AJCC staging manual. Laryngoscope, 2018.

Auditory brainstem implants (ABIs) provide sound awareness to deaf individuals who are not candidates for the cochlear implant. The ABI electrode array rests on the surface of the cochlear nucleus (CN) in the brainstem and delivers multichannel electrical stimulation. The complex anatomy and physiology of the CN, together with poor spatial selectivity of electrical stimulation and inherent stiffness of contemporary multichannel arrays, leads to only modest auditory outcomes among ABI users. Here, we hypothesized that a soft ABI could enhance biomechanical compatibility with the curved CN surface. We developed implantable ABIs that are compatible with surgical handling, conform to the curvature of the CN after placement, and deliver efficient electrical stimulation. The soft ABI array design relies on precise microstructuring of plastic-metal-plastic multilayers to enable mechanical compliance, patterning, and electrical function. We fabricated soft ABIs to the scale of mouse and human CN and validated them in vitro. Experiments in mice demonstrated that these implants reliably evoked auditory neural activity over 1 month in vivo. Evaluation in human cadaveric models confirmed compatibility after insertion using an endoscopic-assisted craniotomy surgery, ease of array positioning, and robustness and reliability of the soft electrodes. This neurotechnology offers an opportunity to treat deafness in patients who are not candidates for the cochlear implant, and the design and manufacturing principles are broadly applicable to implantable soft bioelectronics throughout the central and peripheral nervous system.

Objectives/Hypothesis: To investigate the definition of a clear margin and the use of frozen section (FS) among practicing head and neck surgeons in oral cancer management. Study Design: Cross-sectional survey. Methods: We designed a survey that was sent to American Head and Neck Society (AHNS) members via an email link. Results: A total of 185 (13% of 1,392) AHNS members completed our survey. Most surgeons surveyed (96.8%) use FS to supplement oral cavity squamous cell carcinoma resections. Fifty-five percent prefer a specimen-based approach. The majority of respondents believe FS is efficacious in guiding re-resection of positive margins, with 81% considering the new margin to be negative. More than half of respondents defined a distance of >5 mm on microscopic examination as a negative margin. Conclusions: To avoid oral cancer resections that result in positive margins on final analysis, and thus the need for additional therapy, most surgeons surveyed use FS. A majority of surveyed surgeons now prefer a specimen-based approach to margin assessment. Although there is a debate on what constitutes a negative margin, most surgeons surveyed believe it to be >5 mm on microscopic examination.

The current standard of care in oral tongue cancer surgery is complete resection with a target of 5-mm microscopic clearance at all margins on final pathologic review. While current methods of resection are often successful at determining the mucosal margins of the lesion, they may be limited when attempting to achieve an adequate deep margin. A number of previous studies suggested that ultrasound is superior to manual palpation and other imaging modalities (computed tomography, magnetic resonance imaging) at demarcating the margins of tongue lesions. Recent clinical reports of the intraoperative use of this modality have used an invasive method to mark the proposed deep resection margin. In this communication, we report our initial experience with the use of intraoperative ultrasound as an adjunct to oral tongue cancer surgery without the use of an invasive method to mark the deep resection margin.

This is the largest study to date examining the usefulness of cVEMPs in the diagnosis of SCD. Our "third window indicator" (TWI) combines cVEMP thresholds with the ABG at 250 Hz to improve the ability to screen patients with SCD symptoms.