Faculty Bibliography

OBJECTIVES: Five databases were mined to examine distributions of air-bone gaps obtained by automated and manual audiometry. Differences in distribution characteristics were examined for evidence of influences unrelated to the audibility of test signals. DESIGN: The databases provided air- and bone-conduction thresholds that permitted examination of air-bone gap distributions that were free of ceiling and floor effects. Cases with conductive hearing loss were eliminated based on air-bone gaps, tympanometry, and otoscopy, when available. The analysis is based on 2,378,921 threshold determinations from 721,831 subjects from five databases. RESULTS: Automated audiometry produced air-bone gaps that were normally distributed suggesting that air- and bone-conduction thresholds are normally distributed. Manual audiometry produced air-bone gaps that were not normally distributed and show evidence of biasing effects of assumptions of expected results. In one database, the form of the distributions showed evidence of inclusion of conductive hearing losses. CONCLUSIONS: Thresholds obtained by manual audiometry show tester bias effects from assumptions of the patient's hearing loss characteristics. Tester bias artificially reduces the variance of bone-conduction thresholds and the resulting air-bone gaps. Because the automated method is free of bias from assumptions of expected results, these distributions are hypothesized to reflect the true variability of air- and bone-conduction thresholds and the resulting air-bone gaps.

BACKGROUND: Whether elective lymph neck dissection (ELND) is associated with improved survival in oral squamous cell carcinomas (SCC) of the maxillary alveolus/hard palate is not known. METHODS: One hundred ninety-nine patients presenting de novo and receiving treatment for clinically node negative SCC of the maxillary alveolus/hard palate at 2 cancer centers between 1985 and 2011 were analyzed. RESULTS: Forty-two patients (21%) received ELND. Occult nodal metastases were present in 29% of the dissected necks. The ELND group had more T3 to T4 status tumors (62% vs 34%; p < .001) and positive-margin resections (59% vs 38%; p = .019). Patients undergoing ELND experienced lower rates of neck recurrence (6% vs 21%; p = .031), superior 5-year recurrence-free survival (68% vs 45%; p = .026), and overall survival (86% vs 62%; p = .043). ELND was associated with a 2-fold decrease in risk of recurrence in multivariable analysis. CONCLUSION: ELND was associated with lower rates of recurrence and improved survival in SCC of the maxillary alveolus/hard palate. (c) 2015 Wiley Periodicals, Inc. Head Neck, 2015.

The aim of this study was to evaluate the impact of BRAF inhibitors on survival outcomes in patients receiving stereotactic radiosurgery (SRS) for melanoma brain metastases. We prospectively collected treatment parameters and outcomes for 80 patients with melanoma brain metastases who underwent SRS. Thirty-five patients harbored the BRAF mutation (BRAF-M) and 45 patients did not (BRAF-WT). Univariate and multivariate analyses were performed to identify predictors of overall survival. The median overall survival from first SRS procedure was 6.7, 11.2 months if treated with a BRAF inhibitor and 4.5 months for BRAF-WT. Actuarial survival rates for BRAF-M patients on an inhibitor were 54 % at 6 months and 41 % at 12 months from the time of SRS. In contrast, BRAF-WT had overall survival rates of 28 % at 6 months and 19 % at 12 months. Overall survival was extended for patients on a BRAF inhibitor at or after the first SRS. The median time to intracranial progression was 3.9 months on a BRAF inhibitor and 1.7 months without. The local control rate for all treated tumors was 92.5 %, with no difference based on BRAF status. Patients with higher KPS, fewer treated intracranial metastases, controlled systemic disease, RPA Class 1 and BRAF-M patients had extended overall survival. Overall, patients with BRAF-M treated with both SRS and BRAF inhibitors, at or after SRS, have increased overall survival from the time of SRS. As patients live longer as a result of more effective systemic and local therapies, close surveillance and early management of intracranial disease with SRS will become increasingly important.

OBJECTIVES/HYPOTHESIS: To describe the management and outcomes of Fanconi anemia (FA) patients with head and neck squamous cell carcinoma. STUDY DESIGN: Cohort study. METHODS: Demographic information, prognostic factors, therapeutic management, and survival outcomes for FA patients enrolled in the International Fanconi Anemia Registry who developed head and neck squamous cell carcinoma (HNSCC) were analyzed. RESULTS: Thirty-five FA patients were diagnosed with HNSCC at a mean age of 32 years. The most common site of primary cancer was the oral cavity (26 of 35, 74%). Thirty patients underwent surgical resection of the cancer. Sixteen patients received radiation therapy with an average radiation dose of 5,050 cGy. The most common toxicities were high-grade mucositis (9 of 16, 56%), hematologic abnormalities (8 of 16, 50%), and dysphagia (8 of 16, 50%). Three patients received conventional chemotherapy and had significant complications, whereas three patients who received targeted chemotherapy with cetuximab had fewer toxicities. The 5-year overall survival rate was 39%, with a cause-specific survival rate of 47%. CONCLUSIONS: Fanconi anemia patients have a high risk of developing aggressive HNSCC at an early age. Fanconi anemia patients can tolerate complex ablative and reconstructive surgeries, but careful postoperative care is required to reduce morbidity. The treatment of FA-associated HNSCC is difficult secondary to the poor tolerance of radiation and chemotherapy. However, radiation should be used for high-risk cancers due to the poor survival in these patients. LEVEL OF EVIDENCE: 4. Laryngoscope, 2015.

IMPORTANCE: Limited information exists regarding clinical outcomes of children undergoing extracapsular tonsillectomy and adenoidectomy (ETA) or intracapsular tonsillectomy and adenoidectomy (ITA) for treatment of obstructive sleep apnea syndrome (OSAS). OBJECTIVES: To quantify polysomnography (PSG) and clinical outcomes of ETA and ITA in children with OSAS and to assess the contribution of comorbid conditions of asthma and obesity. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using medical records at a tertiary pediatrics inner-city hospital. Medical records from 89 children who underwent ETA or ITA between October 1, 2008, and December 31, 2013, were analyzed. The dates of our analysis were January 6, 2014, to April 11, 2014. Inclusion criteria required no evidence of craniofacial or neurological disorders, confirmation of OSAS by PSG within the 2 years before surgery, and a second PSG within the 2 years after surgery. INTERVENTIONS: Each child underwent ETA or ITA after being evaluated by a pediatric otolaryngologist and obtaining written parental informed consent. MAIN OUTCOMES AND MEASURES: Main primary outcomes were derived from PSG. Secondary outcomes included treatment failure, defined as residual OSAS with an obstructive apnea-hypopnea index of at least 5 events per hour. Comparisons were made between and within groups. Logistic regression was used to identify factors associated with treatment failure. RESULTS: Fifty-two children underwent ETA, and 37 children underwent ITA. Children in the ETA group were older (7.5 vs 5.2 years, P = .001) and more obese (60% [31 of 52] vs 30% [11 of 37], P = .004). However, both groups had similar severity of OSAS, with median preoperative obstructive apnea-hypopnea indexes of 17.0 in the ETA group and 24.1 in the ITA group (P = .21), and similar prevalences of asthma (38% [20 of 52] vs 38% [14 of 37]). After surgery, significant improvement was noted on PSG in both groups, with no differences in any clinical outcomes. There was no association between procedure type, age, or body mass index z score and treatment failure. However, in a subset of patients with asthma and obesity, ITA was associated with residual OSAS (odds ratio, 16.5; 95% CI, 1.1-250.2; P = .04). CONCLUSIONS AND RELEVANCE: Both ETA and ITA are effective modalities to treat OSAS, with comparable surgical outcomes on short-term follow-up. However, when comorbid diagnoses of both asthma and obesity exist, OSAS is likely to be refractory to treatment with ITA compared with ETA.

OBJECTIVE: To compare 2 surgical techniques for implantation of a percutaneous bone anchored hearing device: (1) a minimal skin punch incision without additional skin incision or soft tissue reduction and (2) implantation with an epidermal flap and soft tissues reduction. STUDY DESIGN: Prospective study. SETTING: Tertiary care referral center. SUBJECTS AND METHODS: Forty patients consecutively implanted (18 males and 22 females). Twenty patients underwent implantation by means of epidermal flap and soft tissues reduction (dermatome group), and 20 patients underwent skin punch resection without soft tissues reduction (punch group). MAIN OUTCOME MEASUREMENTS: surgical adverse events, surgical time, skin healing, skin tolerance (Holgers classification), and skin appearance and implant failure. RESULTS: The surgical time was shorter with the punch technique (P < .05). The postoperative healing was satisfactory in both groups. All implants were loaded after the healing period. The skin tolerance was good in both groups by Holgers classification (punch, 85.7%/dermatome, 86%) with no significant difference. There were no severe adverse skin events in the punch group. The appearance of the skin around the implant was improved by the punch technique. CONCLUSION: The implantation of the currently available percutaneous bone anchored hearing implants with a minimal skin punch skin resection without additional skin incision or soft tissue reduction shortens the surgery and improves the postoperative appearance. The skin tolerance is at least as good as with techniques with that include soft tissue reduction.

OBJECTIVE: Micro-electrocorticography (muECoG) offers a minimally invasive neural interface with high spatial resolution over large areas of cortex. However, electrode arrays with many contacts that are individually wired to external recording systems are cumbersome and make recordings in freely behaving rodents challenging. We report a novel high-density 60-electrode system for muECoG recording in freely moving rats. APPROACH: Multiplexed headstages overcome the problem of wiring complexity by combining signals from many electrodes to a smaller number of connections. We have developed a low-cost, multiplexed recording system with 60 contacts at 406 mum spacing. We characterized the quality of the electrode signals using multiple metrics that tracked spatial variation, evoked-response detectability, and decoding value. Performance of the system was validated both in anesthetized animals and freely moving awake animals. MAIN RESULTS: We recorded muECoG signals over the primary auditory cortex, measuring responses to acoustic stimuli across all channels. Single-trial responses had high signal-to-noise ratios (SNR) (up to 25 dB under anesthesia), and were used to rapidly measure network topography within approximately 10 s by constructing all single-channel receptive fields in parallel. We characterized evoked potential amplitudes and spatial correlations across the array in the anesthetized and awake animals. Recording quality in awake animals was stable for at least 30 days. Finally, we used these responses to accurately decode auditory stimuli on single trials. SIGNIFICANCE: This study introduces (1) a muECoG recording system based on practical hardware design and (2) a rigorous analytical method for characterizing the signal characteristics of muECoG electrode arrays. This methodology can be applied to evaluate the fidelity and lifetime of any muECoG electrode array. Our muECoG-based recording system is accessible and will be useful for studies of perception and decision-making in rodents, particularly over the entire time course of behavioral training and learning.

OBJECTIVE: To evaluate the association of body mass index (BMI) and spermatic vein diameters (SVDs) in men treated for varicocele. SUBJECTS AND METHODS: One hundred fourteen men who underwent scrotal color duplex ultrasounds prior to microsurgical varicocelectomy were classified as normal (BMI = 18.5-24.9), overweight (25-29.9), or obese (>/=30). SVDs were measured with and without Valsalva, standing and supine. SVD, pre- and postoperative semen analyses (SA) were compared. RESULTS: Forty-six (40.4%) men had normal BMI, 54 (47.3%) were overweight, and 14 (12.3%) were obese. Higher BMI was associated with smaller left testis volume and larger left SVD when supine (with and without Valsalva). The association was absent when standing. Men with higher BMI had smaller differences between their left SVD Valsalva diameters when standing vs supine. There were no differences among BMI classes for right SVD measurements, preoperative SA, and postoperative SA improvement. CONCLUSION: Increased BMI is associated with larger left SVD while supine, suggesting that increased abdominal pressure while recumbent may contribute to varicocele pathology in this population. Interestingly, as in the general population, a majority of the men were overweight.

Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery.