Faculty Bibliography

Objective. To determine the efficacy of small interfering RNA (siRNA) targeting Smad3 to mediate fibroplasia in vitro, to investigate the temporal regulation of Smad3 following vocal fold (VF) injury, and to determine the local and distal effects of Smad3 siRNA vocal fold injection. Study Design. In vitro and in vivo Methods. In vitro, Smad3 regulation was examined at both the level of transcription and translation in a human VF cell line in response to Smad3 siRNA +/- TGF-beta.Collagen transcription was also examined. In vivo, Smad3 mRNA expression was quantified as a function of time following rabbit VF injury. Also, the effects of injected Smad3 siRNA were assessed at local and distal sites. Results. Smad3 siRNA knocked down Smad3 transcription and translation and limited TGF-beta mediated collagen mRNA expression with minimal cytotoxicity in vitro. In vivo, Smad3 mRNA increased 1 day following VF injury and remained elevated through day 7. Smad3 siRNA injection into the uninjured vocal fold had no local or distant effect on Smad3 mRNA at multiple organ sites. Conclusion. These data provide a foundation for further investigation regarding the development of novel RNA-based therapeutics for the VF, specifically locally-delivered siRNA for challenging fibrotic conditions of the VF.

Objective. To evaluate risk factors strongly associated with Adult-Onset Recurrent Respiratory Papillomatosis (AO-RPP). Study Design. Prospective, age and sex-matched, case-control Methods. Patients with AO-RRP and controls completed a computer-based, 89-item questionnaire across three academic institutions. Results. Forty-eight AO-RRP patients were compared to 73 controls; 43 of the 48 AO-RRP patients were male (89.5%). The difference in the median number of lifetime sexual partners between AO-RRP (15) and controls (10) was significant (p=0.0387). Additionally, an increased number lifetime sexual partners (>/=26) was associated with AO-RRP. No significant difference for the number of lifetime oral sex partners was observed between groups. Increased comorbidity, as quantified by the Charleson Comorbidity Index, was observed in patients with AO-RRP. AO-RRP and control groups were similar across many other variables including birth history, smoking history, alcohol use, drug use, education, income, and SF-36 scores. Conclusion. AO-RRP was not associated with previously-proposed risk factors for juvenile-onset RRP and may be associated with an increased number of lifetime sexual partners.

PURPOSE OF REVIEW: To summarize the recent medical literature related to the feasibility of hearing preservation after cochlear implantation and to identify variables that may influence hearing preservation in the implanted ear as well as the hearing perception outcomes. RECENT FINDINGS: The published data provide evidence that hearing preservation in the implanted ear yields significantly higher levels of speech recognition in complex listening environments than having just monaural acoustic hearing. There is ample evidence that hearing preservation is feasible and the reported rate is 50-89% in the low frequencies. This rate tends to be stable over time, except for a small percentage that diminishes around 3 months of follow-up. However, factors or variables which influence hearing preservation are yet unknown. Variables such as patient age, degree of residual hearing, insertion depth, insertion speed, duration of profound high frequency deafness and electrode design have been proposed. SUMMARY: Much attention has been focused on hearing preservation in the implanted ear. Thus, investigations into electrode array design, surgical technique and pharmacological management have been undertaken. Minimizing damage in the inner ear not only enhances the possibility for hearing preservation and better performance in complex listening scenarios but also conserves inner ear structures for future treatments.

Humans have the capacity to evaluate the success of cognitive processes, known as metacognition. Convergent evidence supports a role for anterior prefrontal cortex in metacognitive judgements of perceptual processes. However, it is unknown whether metacognition is a global phenomenon, with anterior prefrontal cortex supporting metacognition across domains, or whether it relies on domain-specific neural substrates. To address this question, we measured metacognitive accuracy in patients with lesions to anterior prefrontal cortex (n = 7) in two distinct domains, perception and memory, by assessing the correspondence between objective performance and subjective ratings of performance. Despite performing equivalently to a comparison group with temporal lobe lesions (n = 11) and healthy controls (n = 19), patients with lesions to the anterior prefrontal cortex showed a selective deficit in perceptual metacognitive accuracy (meta-d'/d', 95% confidence interval 0.28-0.64). Crucially, however, the anterior prefrontal cortex lesion group's metacognitive accuracy on an equivalent memory task remained unimpaired (meta-d'/d', 95% confidence interval 0.78-1.29). Metacognitive accuracy in the temporal lobe group was intact in both domains. Our results support a causal role for anterior prefrontal cortex in perceptual metacognition, and indicate that the neural architecture of metacognition, while often considered global and domain-general, comprises domain-specific components that may be differentially affected by neurological insult.

The global burden of cancer pain is enormous and opioids, despite their side effects, remain the primary therapeutic approach. The cause of cancer pain is unknown. Mechanisms driving cancer pain differ from those mechanisms responsible for inflammatory and neuropathic pain. The prevailing hypothesis put forward to explain cancer pain posits that cancers generate and secrete mediators which sensitize and activate primary afferent nociceptors in the cancer microenvironment. Moreover, cancers induce neurochemical reorganization of the spinal cord, which contributes to spontaneous activity and enhanced responsiveness. The purpose of this review, which covers clinical and preclinical studies, is to highlight those peripheral and central mechanisms responsible for cancer pain. The challenges facing neuroscientists and clinicians studying and ultimately treating cancer pain are discussed.

BACKGROUND: The free fibula osteocutaneous flap has become the criterion standard for reconstruction of complex mandibular defects. The authors present their institutional experience with optimization of flap contouring and inset using virtual planning and prefabricated cutting jigs. METHODS: All free fibula-based mandible reconstructions performed at the authors' institution using virtual planning technology between 2009 and 2012 were retrospectively analyzed. The authors evaluated a variety of patient and procedural variables and outcomes. A series of cases performed before virtual planning was reviewed for comparison purposes. RESULTS: Fifty-four reconstructions were performed in 52 patients. Patients were divided evenly between a private university-affiliated medical center and a large county hospital. The most common indications were malignancy (43 percent), ameloblastoma (26 percent), and osteonecrosis/osteomyelitis (23 percent). Thirty percent of patients had irradiation of the recipient site and 38 percent had previous surgery. Sixty-three percent of patients received dental implants, with 47 percent achieving functional dentition. Twenty-five percent of patients had immediate dental implant placement, and 9 percent had immediate dental restoration. Postoperative imaging demonstrated excellent precision and accuracy of flap positioning. Comparison with cases performed before virtual planning demonstrated increased complexity of flap design along with reduced operative time in the virtually planned group. CONCLUSIONS: Preoperative virtual planning along with use of prefabricated cutting jigs allows for precise contouring and positioning of microvascular fibula free flaps in mandibular reconstruction. Using this technique, the authors have achieved unprecedented rates of dental rehabilitation along with reduced operative times. The authors believe that virtual planning technologies are an emerging criterion standard in mandible reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

IMPORTANCE/OBJECTIVE:Prior to applying or interviewing, most prospective applicants turn to the Internet when evaluating residency programs, making maintenance of a comprehensive website critical. While certain "intangibles" such as reputation may not be communicated effectively online, residency websites are invaluable for conveying other aspects of a program. Prior analyses have reported that certain criteria such as research experience and didactics are important considerations for applicants. OBJECTIVE:To evaluate the comprehensiveness of otolaryngology residency websites. DESIGN AND PARTICIPANTS/METHODS:Review of otolaryngology residency program websites. Websites of 99 civilian residency programs were searched for the presence of 23 criteria. MAIN OUTCOMES AND MEASURES/METHODS:Presence of 23 criteria for application process, incentives, instruction, research, clinical training, and other. RESULTS:Only 5 programs contained at least three-quarters of the criteria analyzed; on average programs reported less than 50% of information sought. Among the 99 residency program websites, a description of the following criteria was noted: comprehensive faculty listing (88%), didactics (80%), contact e-mail (77%), current residents (74%), description of facilities (70%), intern schedule (70%), research requirements (69%), otolaryngology rotation schedule (64%), other courses (61%), ERAS (Electronic Residency Application Service) link (55%), year-to-year responsibility progression (47%), call schedule (40%), active/past research projects (37%), area information (34%), message from the program director (33%) or chair (23%), selection criteria (30%), salary (directly on site) (23%), surgical statistics (18%), parking (9%), and meal allowance (7%). The mean (SD) percentage present of factors encompassing "clinical training" was 55% (23%), significantly higher than the mean (SD) percentage of factors covered under the "incentives" category (19% [11%]; P = .01). The proportion of overall criteria present on websites did not differ on organizing programs by region (range, 42%-49%). Sites for "large" programs (≥3 residents per year) were more comprehensive (49% vs 42%; P = .04). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:While further survey of prospective applicants would be invaluable in determining which factors are of greatest interest, many residency websites appear to be inadequately comprehensive. Despite the relative comprehensiveness of criteria relevant to clinical training when compared with other aspects of websites such as incentives, several crucial aspects of training are still not addressed in many sites.