Faculty Bibliography

OBJECTIVES/OBJECTIVE:The application of laser (light amplification by stimulated emission of radiation) energy in the larynx relies on thermal injury. The impact of this injury on adjacent tissue can be undesirable. Attempts have been made to limit the extent and range of injury to adjacent tissue. The O-Pel Surgical System (Precise Light Surgical, Inc., Campbell, CA), a new technology, utilizes kinetic energy through Pressure Induced Tissue Resection (PITR) (Precise Light Surgical, Inc.) to cut tissue, theoretically eliminating injury to adjacent tissue. The purpose of this study was to evaluate the PSL in canine vocal folds. METHODS:Four dogs underwent PITR incisions (4 mJ pulses at 200 Hz) on their vocal folds, through mucosa into the muscle. The animals were sacrificed at days 0, 3, 7, and 21 days postsurgery. The larynges were harvested and histology was performed with hematoxylin and eosin, Masson trichrome, and Verhoeff-van Gieson. RESULTS:At day 0, focal denudation of the epithelium and coagulation necrosis in the lamina propria and adjacent connective tissue are noted. On days 3 and 7, an inflammatory infiltrate of neutrophils is seen within the lamina propria and surrounding connective tissue with minimal edema and early deposition of collagen. At day 21, the mucosa is completely regenerated with the area of previous PITR into the muscle replaced with thick bundles of collagen. CONCLUSION/CONCLUSIONS:The unique PITR characteristics offer a potentially unique cutting technology for laryngeal microsurgery. The current canine study suggests appropriate and rapid healing. With refinements of the tip size of the probe and adjustment of energy, PITR will likely be an appropriate alternate to traditional lasers in laryngeal surgery. LEVEL OF EVIDENCE/METHODS:NA. Laryngoscope, 2019.

Introduction: The mammalian enteric nervous system (ENS) regulates intestinal function in response to luminal changes in nutrients and microbiota. The ENS also modulates immune cells to control microbial homeostasis and fight infections. Enteric neurons signal to the brain via the vagus nerve, providing a mechanism by which microbiota can influence neural activity and behavior at homeostasis or during infections with gut pathogens. However, little is known about the relation between vagus nerve activity and 'sickness behaviors' such as decreased attention, increased irritability and depression, and decreased interest and energy. Here we aimed to record vagus nerve responses in behaving animals towards understanding this gut-brain signaling connection in sickness behavior. Method(s): Custom nerve cuff electrodes were used to monitor vagus nerve activity of wild-type male mice. Cuffs were made with 0.2 mm micro-renathane tubing to surround the upper branch of the sensory vagus nerve and connected to socket gold pins and medwire. Chronic nerve cuffs were implanted in mice aged 6-12 weeks. Surgery consisted of securing gold pins to the cranial vertex and connecting electrodes to the vagus nerve in the neck, around which the cuff was placed. The grounding wire was secured near the cuff. One to two weeks post-surgery, each mouse underwent sickness induction via lipopolysaccharide (LPS) injection. LPS solution was formulated with 9.5/g muL of 0.9% saline solution and 0.5/g muL of pure LPS via intraperitoneal injection. Electrophysiological activity of the vagus nerve was recorded together with video monitoring of behavior, prior to injection to first establish a baseline, and post-injection activity was recorded for up to 24 hours. Sickness behavior was ethogrammed and neural activity analyzed in each animal. Result(s): LPS injection led to reduction of several different behaviors including overall motion in the homecage for hours afterwards. Analysis of simultaneously-recorded vagus activity is ongoing. Conclusion(s): We here describe an integrated system that combines long-term videography and behavioral analysis with recordings of the peripheral nerve activity using a custom chronic nerve cuff for the mouse vagus. Using this system, we have begun to relate neural activity in the sensory vagus to physiological state and behavioral changes in mice for the first time.

Introduction: Vagus nerve stimulation is currently used as a medical treatment for those suffering from severe epilepsy or depression, but the mechanisms underlying vagus nerve stimulation are poorly understood. The vagus nerve helps connect essentially all peripheral organs to the central nervous system, sending afferents to the nucleus tractus solitarius. Recent studies indicate that vagus nerve stimulation can produce long-lasting plasticity in the cerebral cortex, leading to improved sensory processing and recovery of motor behavior after stroke (Boreland et al, Brain Stimul (2016). An understanding of the circuit mechanisms by which vagus nerve stimulation can produce these results would be important for enhancing behavioral outcomes and developing less invasive or non-invasive neuromodulatory therapeutic techniques. Method(s): Studies in mice provide an opportunity for monitoring and manipulating various aspects of neural circuits involved in behavior. One difficulty in the mouse model is the lack of vagus nerve cuff electrodes given the small size of the mouse vagus nerve. We first built a novel vagus nerve cuff electrode for mice and demonstrated reliable low-impedance recordings and stimulation during behavior in mice chronically implanted for months. Two-photon imaging of the auditory cortex was used to track neural responses to tones paired with vagus nerve stimulation. Animals are then trained on either a paired go/no-go or two-alternative forced choice auditory detection and recognition task (Martins and Froemke, Nat Neurosci 2015; Kuchibhotla et al. Nat Neurosci 2017). Result(s): Stimulation of the vagus nerve was calibrated to transiently reduce respiration without affecting other physiological processes (e.g., heart rate). Using two-photon imaging, we found that pairing target tones with vagus nerve stimulation for five minutes led to a short-term enhancement of sensory responses in the mouse auditory cortex. After several days of these brief 5-minute pairing sessions, long-term plasticity was observed with increases in representation of the target tone for at least days thereafter. Conclusion(s): These changes are reminiscent of the effects of basal forebrain stimulation (Froemke et al. Nature 2007) and we are now investigating how vagus nerve stimulation might lead to direct or indirect activation of central modulatory systems to improve plasticity and behavior in mice.

BACKGROUND:Oral human papillomavirus (HPV) infection is the principal underlying cause of a dramatic increase in oropharyngeal cancer. Dentistry can play an important role in developing clinical algorithms for secondary prevention. METHODS:The authors conducted this cross-sectional pilot study with practices of The National Dental Practice-Based Research Network. The authors evaluated the feasibility and acceptability of screening and testing procedures as judged by practitioners and patients. The authors used tablet devices for patient screening, obtaining consent, and administering a confidential oral HPV risk factor survey. RESULTS:Most patients (85%) were comfortable being asked about their cigarette use and their sexual behavior (69%) and were interested in participating again (79%). More than 90% of practitioners were comfortable with study procedures except the extra time required for patient participation (75% comfortable). There were no problems with oral rinse collection as reported by patients or practitioners. CONCLUSIONS:It is feasible in community dental offices to collect oral rinses for HPV detection and to ask patients explicit questions about sexual history when using a tablet device for confidentiality. PRACTICAL IMPLICATIONS/CONCLUSIONS:Discussing high-risk types of HPV and appropriately assessing that risk are a challenge for oral health care professionals. These results are positive from a research perspective but do not address the advisability of routine HPV screening in dentistry.

Neurons recorded in behaving animals often do not discernibly respond to sensory input and are not overtly task-modulated. These non-classically responsive neurons are difficult to interpret and are typically neglected from analysis, confounding attempts to connect neural activity to perception and behavior. Here we describe a trial-by-trial, spike-timing-based algorithm to reveal the coding capacities of these neurons in auditory and frontal cortex of behaving rats. Classically responsive and non-classically responsive cells contained significant information about sensory stimuli and behavioral decisions. Stimulus category was more accurately represented in frontal cortex than auditory cortex, via ensembles of non-classically responsive cells coordinating the behavioral meaning of spike timings on correct but not error trials. This unbiased approach allows the contribution of all recorded neurons - particularly those without obvious task-related, trial-averaged firing rate modulation - to be assessed for behavioral relevance on single trials.

OBJECTIVE:Examine the relationship between duration of unilateral deafness and speech perception outcomes after cochlear implantation in adults with single-sided deafness. METHODS:A systematic review of PubMed articles containing individual speech perception and duration of deafness data from single-sided deaf adults. Studies were selected for detailed review and duration of deafness and speech perception outcomes were extracted, with speech scores reported as percent correct. A linear regression as a function of study and length of deafness was performed. RESULTS:A statistically significant negative effect of duration of unilateral deafness on speech perception was found, but there was substantial uncertainty regarding the strength of the effect. DISCUSSION/CONCLUSIONS:Existing data make it difficult to either support or reject a hard 5- or 10-year unilateral auditory deprivation limit on cochlear implant (CI) candidacy for patients with single-sided deafness. This is because the totality of available data are consistent with a very small effect, perhaps negligible in practical terms, and just as consistent with a very large effect. Regardless of effect size, the present results have important basic implications. They suggest that unilateral sound deprivation may have a deleterious effect on auditory processing even though more central parts of the auditory system have continued to receive input from a contralateral normal ear. CONCLUSIONS:Speech perception scores in SSD patients are negatively correlated with duration of deafness, but the limited amount of data from cochlear implant users with long-term single-sided deafness leads to substantial uncertainly, which in turn precludes any strong clinical recommendations. Further study of SSD CI users with long-term deafness will be necessary to generate evidence-based guidelines for implantation criteria in this population.

OBJECTIVES/OBJECTIVE:The medial sural artery perforator (MSAP) free flap is an uncommonly utilized soft tissue flap in head and neck reconstruction. It is a thin, pliable, fasciocutaneous flap that provides significant pedicle length. The donor site can be closed primarily, and its location is more aesthetically pleasing to patients. We aim to describe the MSAP flap and compare it to other commonly used free flaps in the head and neck. STUDY DESIGN/METHODS:Retrospective case series. METHODS:A retrospective review of all MSAP cases performed at New York University Langone Health was performed from July 2016 to November 2017. We examined the patients' age, diagnosis, history of prior radiation therapy, and comorbidities, as well as flap-specific information and recipient site. RESULTS:(15 cm × 8 cm). The flaps ranged from 5 to 12 mm in thickness. Venous coupler size ranged from 2.0 to 3.5 mm. Primary closure of the donor site was achieved in 18 of 21 flaps. Twenty of 21 flaps were transferred successfully. CONCLUSION/CONCLUSIONS:The MSAP flap is a highly versatile and reliable option for a thin, pliable soft tissue flap with a donor site that may be preferable over the radial forearm free flap and anterolateral thigh flap in complex head and neck reconstruction. LEVEL OF EVIDENCE/METHODS:4. Laryngoscope, 2018.

Perineural invasion (PNI), the neoplastic invasion of nerves, is a common pathological finding in head and neck cancer that is associated with poor clinical outcomes. PNI is a histological finding of tumor cell infiltration and is distinct from perineural tumor spread (PNTS), which is macroscopic tumor involvement along a nerve extending from the primary tumor that is by definition more advanced, being radiologically or clinically apparent. Despite widespread acknowledgement of the prognostic significance of PNI/PNTS, the mechanisms underlying its pathogenesis remain largely unknown, and specific therapies targeting nerve invasion are lacking. The use of radiation therapy for PNI/PNTS can improve local control and reduce devastating failures at the skull base. However, the optimal volumes to be delineated with respect to targeting cranial nerve pathways are not well defined, and radiation may carry risks of major toxicity secondary to the location of adjacent critical structures. Here we examine the pathogenesis of these phenomena, analyze the role of radiation in PNI/PNTS, and propose guidelines for radiation treatment design based on the best available evidence and the authors' collective experience in order to advance understanding and therapy of this ominous cancer phenotype.

Facial transplantation provides a functional and aesthetic solution to severe facial disfigurement previously unresolved by conventional reconstruction. Few facial allografts have been ear containing; hence, there is limited knowledge of the postoperative otologic considerations. We describe the case of a 44-year-old man who underwent transplantation of the total face, eyelids, ears, scalp, and skeletal subunits in 2015 after an extensive thermal injury. We detail the patient's transition from osseointegrated prosthetic ears to an ear-containing facial allograft, and describe the unique surgical approach and challenges encountered. Subsequent bilateral revision meatoplasties were performed, which provided relief from stenosis of the external auditory meatus. Laryngoscope, 2018.