Peter A. Benedict

Gender and age predict outcomes of cognitive, balance and vision testing in a multidisciplinary concussion center

OBJECTIVE This study examined components of the Sports Concussion Assessment Tool, 3rd Edition (SCAT3) and a vision-based test of rapid number naming (King-Devick [K-D]) to evaluate sports and non-sports concussion patients in an outpatient, multidisciplinary concussion center. While the Symptom Evaluation, Standardized Assessment of Concussion (SAC), modified Balance Error Scoring System (BESS), and K-D are used typically for sideline assessment, their use in an outpatient clinical setting following concussion has not been widely investigated. METHODS K-D, BESS, SAC, and SCAT3 Symptom Evaluation scores were analyzed for 206 patients who received concussion care at the Concussion Center at NYU Langone Medical Center. Patient age, gender, referral data, mechanism of injury, time between concussive event and first concussion center appointment, and the first specialty service to evaluate each patient were also analyzed. RESULTS In this cohort, Symptom Evaluation scores showed a higher severity and a greater number of symptoms to be associated with older age (r = 0.31, P = 0.002), female gender (P = 0.002, t-test), and longer time between the concussion event and first appointment at the concussion center (r = 0.34, P = 0.008). Performance measures of K-D and BESS also showed associations of worse scores with increasing patient age (r = 0.32-0.54, P ≤ 0.001), but were similar among males and females and across the spectrum of duration since the concussion event. Patients with greater Symptom Severity Scores also had the greatest numbers of referrals to specialty services in the concussion center (r = 0.33, P = 0.0008). Worse Immediate Memory scores on SAC testing correlated with slower K-D times, potentially implicating the dorsolateral prefrontal cortex as a commonly involved brain structure. CONCLUSION This study demonstrates a novel use of sideline concussion assessment tools for evaluation in the outpatient setting, and implicates age and gender as predictors of outcomes for these tests.

SMAD3 expression and regulation of fibroplasia in vocal fold injury

Recent reports highlight the efficacy of small interfering RNA (siRNA) targeting SMAD3 to regulate transforming growth factor β (TGF‐β)‐mediated fibroplasia in vocal fold fibroblasts. The current study sought to investigate SMAD3 expression during wound healing in vivo and quantify the downstream transcriptional events associated with SMAD3 knockdown in vitro.

Nanoparticle delivery of RNA‐based therapeutics to alter the vocal fold tissue response to injury

Our laboratory and others hypothesized that Smad3 is a principle mediator of the fibrotic phenotype in the vocal folds (VFs), and we further posited that alteration of Smad3 expression through short interfering (si)RNA holds therapeutic promise, yet delivery remains challenging. To address this issue, we employed a novel synthetic oligomer, lipitoid, complexed with siRNA to improve stability and cellular uptake with the goal of increased efficiency of RNA‐based therapeutics.

Association of alirocumab therapy with inflammatory lesions of the vocal folds: A case report: Alirocumab Therapy and Vocal Fold Lesions

Therapeutic monocolonal antibodies (MAbs) are a new, rapidly growing class of medications that frequently have poorly characterized side‐effect profiles. We present a patient who developed inflammatory lesions of the vocal folds in temporal relation to the initiation of alirocumab. Lesions of the vocal folds represent a previously unreported adverse effect of alirocumab therapy, making it the second MAb documented with such a side effect. The potential laryngeal effects of alirocumab specifically, and of MAbs more broadly, warrant investigation. Laryngoscope, 127:1652–1654, 2017

The effects of concurrent chemoradiation therapy to the base of tongue in a preclinical model: Effects of CCRT to the Base of Tongue

To develop a clinically relevant model of oropharyngeal concurrent chemoradiation therapy (CCRT) in order to quantify the effects of CCRT on tongue function and structure. CCRT for advanced oropharyngeal cancer commonly leads to tongue base dysfunction and dysphagia. However, no preclinical models currently exist to study the pathophysiology of CCRT‐related morbidity, thereby inhibiting the development of targeted therapeutics.

The malleus to oval window revision stapedotomy: Efficacy and longitudinal study outcome

To determine the longitudinal effectiveness of the malleus to oval window stapedotomy technique among patients undergoing revision surgery when the incus is unavailable.

Laryngeal distribution of recurrent respiratory papillomatosis in a previously untreated cohort

To describe the distribution of recurrent respiratory papillomatosis (RRP) lesions across 21 laryngeal anatomic regions in previously untreated patients at initial presentation to provide insight regarding the natural history of RRP.

Impact of medialization laryngoplasty on dynamic nanomechanical vocal fold structure properties: Laryngoplasty and nano-DMA VF Structure

Although the primary goal of medialization laryngoplasty is to improve glottic closure, implant placement is also likely to alter the biomechanical properties of the vocal fold (VF). We sought to employ novel, nanoscale technology to quantify these properties following medialization based on the hypothesis that different medialization materials will likely yield differential biomechanical effects.

Morbidity and mortality associated with preclinical tracheostomy models

A secure airway is critical to study obstructive disorders of the larynx and trachea in preclinical models. Tracheostomy has been described in rabbits, swine, canines, and other mammals using tracheostomy tubes or permanent stomas. No studies specifically evaluated morbidity and mortality associated with these models, and existing studies using tracheostomy make little mention of tracheostomy‐related complications. We assessed the management, complications, and mortality associated with tracheostomy in a rabbit model that has recently gained significant attention.

Imiquimod Injection to Rabbit Vocal Folds: A Preliminary, Preclinical Investigation

Objective Given the recalcitrant nature of recurrent respiratory papillomatosis, targeted therapies to reduce disease burden are fundamental to improved patient care paradigms. We seek to demonstrate the safety of imiquimod injection into vocal fold mucosa by evaluating the degree of laryngeal edema, histopathologic changes to vocal fold structure, and serologic interferon α (IFNα) levels following injection. Study Design Preclinical. Setting Academic institution. Subjects and Methods Six New Zealand White rabbits underwent unilateral injection of 100 µg of sterile imiquimod (1 µg/µL), with 100 µL of normal saline injected into the contralateral vocal fold. Direct laryngoscopy was performed on days 3, 7, and 30 following injection. Larynges from 3 rabbits were harvested on postinjection day 7 for histologic analysis. The remaining 3 rabbit larynges were harvested on day 30. Serial serum samples were drawn for IFNα quantification via immunoassay. Results No signs of respiratory distress were observed at any point. Vocal fold appearance was not clinically divergent between imiquimod and control conditions via serial direct laryngoscopic evaluation. No inflammatory lesions or scarring were identified following injection. Histology showed no signs of acute inflammatory processes or changes in the control or imiquimod injection groups. Serum IFNα increased at days 3 and 7 following imiquimod injection (P < .0001 and P = .0368, respectively), before returning to baseline by day 14. Conclusions Vocal fold imiquimod injection did not result in notable morbidity in this preclinical model. However, serum IFNα concentrations increased transiently. These data are critical to advance the therapeutic utility of this compound, particularly in the setting of recurrent respiratory papillomatosis.