Faculty Bibliography

Sudden sensorineural hearing loss (SSNHL) is commonly encountered in audiologic and otolaryngologic practice. SSNHL is most commonly defined as sensorineural hearing loss of 30 dB or greater over at least three contiguous audiometric frequencies occurring within a 72-hr period. Although the differential for SSNHL is vast, for the majority of patients an etiologic factor is not identified. Treatment for SSNHL of known etiology is directed toward that agent, with poor hearing outcomes characteristic for discoverable etiologies that cause inner ear hair cell loss. Steroid therapy is the current mainstay of treatment of idiopathic SSNHL in the United States. The prognosis for hearing recovery for idiopathic SSNHL is dependent on a number of factors including the severity of hearing loss, age, presence of vertigo, and shape of the audiogram.

PURPOSE/OBJECTIVE:Tumor-specific biomarkers that predict resistance to DNA damaging agents may improve therapeutic outcomes by guiding the selection of effective therapies and limiting morbidity related to ineffective approaches. XPF (ERCC4) is an essential component of several DNA repair pathways and XPF-deficient cells are exquisitely sensitive to DNA damaging agents. The purpose of this study was to determine whether XPF expression levels predict clinical response to DNA damaging agents in head and neck squamous cell carcinoma (HNSCC). EXPERIMENTAL DESIGN/METHODS:Quantitative immunohistochemistry was used to measure XPF expression in tumors from a cohort of 80 patients with newly diagnosed HNSCC treated with radiation therapy with or without platinum-based chemotherapy; samples were collected prospectively. Genomic DNA isolated from blood samples was analyzed for nine single nucleotide polymorphisms (SNP) in the XPF gene by using a custom array. The primary endpoint was progression-free survival (PFS). RESULTS:XPF expression was higher in tumors from the oral cavity than from the other sites (P < 0.01). High XPF expression correlated with early time to progression both by univariate (HR = 1.87, P = 0.03) and multivariate analysis (HR = 1.83, P = 0.05). The one year PFS for high expressers was 47% (95% CI = 31-62) compared with 72% (95% CI = 55-83) for low expressers. In addition, we identified four XPF SNPs that showed marginal association with treatment failure. CONCLUSIONS:Expression level of XPF in HNSCC tumors correlates with clinical response to DNA damaging agents. XPF has potential to guide next generation personalized cancer therapy.

Voice deficits are a common complication of both Parkinson disease (PD) and aging; they can significantly diminish quality of life by impacting communication abilities. (1, 2) Targeted training (speech/voice therapy) can improve specific voice deficits,(3, 4) although the underlying mechanisms of behavioral interventions are not well understood. Systematic investigation of voice deficits and therapy should consider many factors that are difficult to control in humans, such as age, home environment, age post-onset of disease, severity of disease, and medications. The method presented here uses an animal model of vocalization that allows for systematic study of how underlying sensorimotor mechanisms change with targeted voice training. The ultrasonic recording and analysis procedures outlined in this protocol are applicable to any investigation of rodent ultrasonic vocalizations. The ultrasonic vocalizations of rodents are emerging as a valuable model to investigate the neural substrates of behavior.(5-8) Both rodent and human vocalizations carry semiotic value and are produced by modifying an egressive airflow with a laryngeal constriction.(9, 10) Thus, rodent vocalizations may be a useful model to study voice deficits in a sensorimotor context. Further, rat models allow us to study the neurobiological underpinnings of recovery from deficits with targeted training. To model PD we use Long-Evans rats (Charles River Laboratories International, Inc.) and induce parkinsonism by a unilateral infusion of 7 mug of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle which causes moderate to severe degeneration of presynaptic striatal neurons (for details see Ciucci, 2010).(11, 12) For our aging model we use the Fischer 344/Brown Norway F1 (National Institute on Aging). Our primary method for eliciting vocalizations is to expose sexually-experienced male rats to sexually receptive female rats. When the male becomes interested in the female, the female is removed and the male continues to vocalize. By rewarding complex vocalizations with food or water, both the number of complex vocalizations and the rate of vocalizations can be increased (Figure 1). An ultrasonic microphone mounted above the male's home cage records the vocalizations. Recording begins after the female rat is removed to isolate the male calls. Vocalizations can be viewed in real time for training or recorded and analyzed offline. By recording and acoustically analyzing vocalizations before and after vocal training, the effects of disease and restoration of normal function with training can be assessed. This model also allows us to relate the observed behavioral (vocal) improvements to changes in the brain and neuromuscular system.

OBJECTIVE: Multi-centre collaborative study to develop and refine the design of a prototype thin perimodiolar cochlear implant electrode array and to assess feasibility for use in human subjects. STUDY DESIGN: Multi-centre temporal bone insertion studies. MATERIALS AND METHODS: The modiolar research array (MRA) is a thin pre-curved electrode that is held straight for initial insertion with an external sheath rather than an internal stylet. Between November 2006 and February 2009, six iterations of electrode design were studied in 21 separate insertion studies in which 140 electrode insertions were performed in 85 human temporal bones by 12 surgeons. These studies aimed at addressing four fundamental questions related to the electrode concept, being: (1) Could a sheath result in additional intra-cochlear trauma? (2) Could a sheath accommodate variations in cochlea size and anatomies? (3) Could a sheath be inserted via the round window? and (4) Could a sheath be safely removed once the electrode had been inserted? These questions were investigated within these studies using a number of evaluation techniques, including X-ray and microfluoroscopy, acrylic fixation and temporal bone histologic sectioning, temporal bone microdissection of cochlear structures with electrode visualization, rotational tomography, and insertion force analysis. RESULTS: Frequent examples of electrode rotation and tip fold-over were demonstrated with the initial designs. This was typically caused by excessive curvature of the electrode tip, and also difficulty in handling of the electrode and sheath. The degree of tip curvature was progressively relaxed in subsequent versions with a corresponding reduction in the frequency of tip fold-over. Modifications to the sheath facilitated electrode insertion and sheath removal. Insertion studies with the final MRA design demonstrated minimal trauma, excellent perimodiolar placement, and very small electrode dimensions within scala tympani. Force measurements in temporal bones demonstrated negligible force on cochlear structures with angular insertion depths of between 390 and 450 degrees . CONCLUSION: The MRA is a novel, very thin perimodiolar prototype electrode array that has been developed using a systematic collaborative approach. The different evaluation techniques employed by the investigators contributed to the early identification of issues and generation of solutions. Regarding the four fundamental questions related to the electrode concept, the studies demonstrated that (1) the sheath did not result in additional intra-cochlear trauma; (2) the sheath could accommodate variations in cochlea size and anatomies; (3) the sheath was more successfully inserted via a cochleostomy than via the round window; and (4) the sheath could be safely removed once the electrode had been inserted

Extracochlear electrode extrusion is a potentially under-recognized complication of cochlear implantation. As the age of implantation becomes younger, electrode extrusion is of concern due to future skull growth. Extrusion of several electrodes may compromise performance and thus require surgical reinsertion of the electrodes. Almost 60% of patients with electrode extrusion have required revision surgery. This paper presents a case report and literature review which discusses factors which contribute to electrode extrusion and emphasizes the need for a high degree of suspicion in certain situations. Surgical steps such as electrode fixation techniques are highlighted in order to attempt to reduce the occurrence of this complication

OBJECTIVE: To document the preservation of hearing after electroacoustic (EAS) cochlear reimplantation and to report on a method of managing recurrent air accumulation under the posterior skin flap. STUDY DESIGN: Retrospective case report. PATIENTS: A single patient report. INTERVENTION: After successful EAS cochlear implantation with hearing preservation, patient developed recurrent air accumulation under his posterior flap and a subsequent device failure. The patient was reimplanted using EAS protocol and a myringotomy tube used to prevent reaccumulation of air. MAIN OUTCOME MEASURE: Preservation of hearing. RESULTS: Hearing was preserved after reimplantation, and air accumulation was avoided. CONCLUSION: Hearing can be preserved in EAS reimplantation using EAS surgical techniques. Air accumulation can be avoided or treated with a myringotomy tube

The micropulsed 1444-nm neodymium-doped lipolysis laser exhibits favorable characteristics for novel application in facial contouring. The study described herein is the first clinical report of laser-assisted facial contouring (LAFC). We retrospectively reviewed records of 478 LAFC patients (mean age 52) who underwent contouring of 1278 individual mid- and lower facial treatment sites over 18 months. Along with clinical assessment, study parameters evaluated among "original" and "modified" (where protocol updates included deep dermal soft tissue coagulation as an optional step) protocol groups included laser power, pulse energy, and total energy delivery as well as lipoaspirate volume at each treatment site. Mean power and pulse energy were similar (within 5%) and total energy use was greater (70% higher for mid- and lower face) in the original protocol group. Lipoaspirate volume was similar for both groups for the midface (within 10%) but elevated in the modified protocol group for the lower face (40% higher). Treatment complications were observed in 47 of 363 treatment sites (13%) in the original and in 12 of 915 treatment sites (1%) in the modified protocol group with the majority (63%) of the complications comprising over- versus undercorrections of desired tissue contour. Clinical efficacy varied with improvements of mid- and/or lower facial contour ranging from marginal to subtle to very apparent. LAFC as detailed herein is a novel treatment modality that enables selective soft tissue removal for greater precision in three-dimensional contouring of the face. Protocol modifications based on laboratory and observed tissue photothermodynamics have improved LAFC safety.

BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is a recognized entity that is increasingly responsible for skin and soft tissue infections. However, it is not the usual pathogen isolated in nasal vestibular abscess. METHODS: We present a series of 13 consecutive patients presenting to a tertiary care center with nasal vestibular abscess over a 2.5-year period. RESULTS: All abscesses were cultured and 100% (13/13) grew S. aureus. Of the S. aureus isolates, 92% (12/13) were MRSA. Antibiotic susceptibilities of the MRSA isolates were as follows: 100% were susceptible to rifampin, trimethoprim-sulfamethoxazole, and tetracycline, 75% to clindamycin, 58% to fluoroquinolones, and 17% to erythromycin. CONCLUSION: MRSA is an important pathogen in the community. It is therefore critical to appreciate its potential predominance in nasal vestibular abscess. Clinicians should obtain cultures, modify antibiotic therapy as warranted, and initiate empiric therapy to include MRSA coverage for nasal vestibular abscess.

Mycotoxins are toxic secondary metabolites produced by a variety of fungi including Aspergillus, Alternaria, and Penicillium species. The presence of mycotoxins in sinonasal tissue and secretions and any possible link to chronic rhinosinusitis (CRS) or other diseases of the head and neck have not been reported. The authors performed an exploratory study to determine the presence and levels of mycotoxins in the sinonasal tissue and secretions of 18 subjects undergoing endoscopic sinus surgery for CRS. Using commercial enzyme-linked immunosorbent assay kits, samples were analyzed for the following mycotoxins: aflatoxin, deoxynivalenol, zearalenone, ochratoxin, and fumonisin. All specimens were negative for aflatoxin, deoxynivalenol, zearalenone, and fumonisin. Four (22%) of 18 specimens were positive for ochratoxin. The clinical significance of this finding remains to be determined