Faculty Bibliography

Hemostasis is a critical component of otologic and neurotologic surgery. In these surgeries the surgical field is small; thus, even a small amount of bleeding can obstruct the view of critical and extremely small structures. Additionally, relatively large vascular structures traverse the area; if they are encroached on by trauma or disease, bleeding must be controlled within a very small space in a meticulous fashion that does not encroach on structures of the middle ear and mastoid. The authors discuss several hemostatic agents in the middle ear, mastoid, and lateral skull base, highlighting their origins, mechanisms, advantages, and complications.

Background The osteocutaneous radial forearm free flap (OCRFFF) for mandibular reconstruction has been well described. Despite this flap's utility in the repair of such defects, the indications for the OCRFFF have continued to expand in recent years. The advantages of the OCRFFF allow for a high degree of versatility in the reconstruction of the various anatomical and aesthetic units of the head and neck. In this review, the authors aim to explore the successful utilization of the OCRFFF beyond the reconstruction of composite mandibular defects. Methods A retrospective chart review was performed. All subjects who underwent OCRFFF reconstruction at a tertiary academic center between January 2004 and December 2014 were identified. A total of six patients undergoing this procedure for indications other than composite mandibular defects of the head and neck were included. Results A total of six patients underwent OCRFFF reconstruction for correction of nonmandibular defects. Flap success was experienced in six of six cases (100%). Indications included midface maxillary reconstruction (N = 2), orbit reconstruction (N = 1), frontal sinus and forehead reconstruction (N = 2), and subglottic stenosis reconstruction (N = 1). There were no immediate perioperative complications. On long-term follow-up, one subject developed a nasocutaneous fistula following radiation and eventually required maxillary hardware removal. Conclusion As a result of its growing role and versatility, the OCRFFF should be incorporated as a multipurpose tool in the armamentarium of reconstructive microvascular surgeons in the repair of composite head and neck defects beyond the mandible.

The zebra finch brain features a set of clearly defined and hierarchically arranged motor nuclei that are selectively responsible for producing singing behavior. One of these regions, a critical forebrain structure called HVC, contains premotor neurons that are active at precise time points during song production. However, the neural representation of this behavior at a population level remains elusive. We used two-photon microscopy to monitor ensemble activity during singing, integrating across multiple trials by adopting a Bayesian inference approach to more precisely estimate burst timing. Additionally, we examined spiking and motor-related synaptic inputs using intracellular recordings during singing. With both experimental approaches, we find that premotor events do not occur preferentially at the onsets or offsets of song syllables or at specific subsyllabic motor landmarks. These results strongly support the notion that HVC projection neurons collectively exhibit a temporal sequence during singing that is uncoupled from ongoing movements.

Oxytocin promotes social interactions and recognition of conspecifics that rely on olfaction in most species. The circuit mechanisms through which oxytocin modifies olfactory processing are incompletely understood. Here, we observed that optogenetically induced oxytocin release enhanced olfactory exploration and same-sex recognition of adult rats. Consistent with oxytocin's function in the anterior olfactory cortex, particularly in social cue processing, region-selective receptor deletion impaired social recognition but left odor discrimination and recognition intact outside a social context. Oxytocin transiently increased the drive of the anterior olfactory cortex projecting to olfactory bulb interneurons. Cortical top-down recruitment of interneurons dynamically enhanced the inhibitory input to olfactory bulb projection neurons and increased the signal-to-noise of their output. In summary, oxytocin generates states for optimized information extraction in an early cortical top-down network that is required for social interactions with potential implications for sensory processing deficits in autism spectrum disorders.

Motor axons approach muscles that are prepatterned in the prospective synaptic region. In mice, prepatterning of acetylcholine receptors requires Lrp4, a LDLR family member, and MuSK, a receptor tyrosine kinase. Lrp4 can bind and stimulate MuSK, strongly suggesting that association between Lrp4 and MuSK, independent of additional ligands, initiates prepatterning in mice. In zebrafish, Wnts, which bind the Frizzled (Fz)-like domain in MuSK, are required for prepatterning, suggesting that Wnts may contribute to prepatterning and neuromuscular development in mammals. We show that prepatterning in mice requires Lrp4 but not the MuSK Fz-like domain. In contrast, prepatterning in zebrafish requires the MuSK Fz-like domain but not Lrp4. Despite these differences, neuromuscular synapse formation in zebrafish and mice share similar mechanisms, requiring Lrp4, MuSK, and neuronal Agrin but not the MuSK Fz-like domain or Wnt production from muscle. Our findings demonstrate that evolutionary divergent mechanisms establish muscle prepatterning in zebrafish and mice.

IMPORTANCE:Salivary duct carcinoma is a rare, aggressive malignancy of the salivary glands. Owing to its rare nature, clinical data are limited, and only a few clinical studies comprise more than 50 patients. OBJECTIVE:To review the University of Pittsburgh Medical Center's experience with salivary duct carcinoma over a 20-year period, focusing on demographics, presentation, treatment, and outcome. DESIGN, SETTING, AND PARTICIPANTS:This investigation was a retrospective cohort study in a multihospital institution with tertiary referral. A pathology database was reviewed for all cases of histopathologically diagnosed salivary duct carcinoma from January 1, 1995, to October 20, 2014. Patients who were referrals for pathology review only and were never seen at the institution were excluded. In total, 75 study patients were identified. The electronic medical record was reviewed for details regarding demographics, presentation, treatment, and outcome, including overall survival (OS) and disease-free survival (DFS). This study was supplemented with a review of the institution's Head and Neck Oncology Database for further clinical details. MAIN OUTCOMES AND MEASURES:Primary outcome measures consisted of OS and DFS. RESULTS:The study sample comprised 75 participants with a mean age at diagnosis of 66.0 years (age range, 33-93 years), and 29% (n = 22) were female. Most primary tumors were from the parotid gland (83%), with the next most frequent site being the submandibular gland (12%). Overall, 41% of the cases were carcinoma ex pleomorphic adenoma. Rates of other histologic features included the following: perineural invasion (69%), extracapsular spread (58%), ERBB2 (formerly HER2) positivity (31%) (62% of those who were tested), and vascular invasion (61%). The median OS was 3.1 years, and the median DFS was 2.7 years. Univariate Kaplan-Meier survival analyses demonstrated that facial nerve sacrifice and extracapsular spread were associated with lower OS (2.38 vs 5.11 years and 2.29 vs 6.56 years, respectively) and DFS (2.4 vs 3.88 years and 1.44 vs 4.5 years, respectively). Although underpowered, multivariable analysis demonstrated significantly worse OS in patients with N2 and N3 disease (hazard ratio [HR] 8.42, 95% CI, 1.84-38.5) but did not show significantly worse DFS or OS for facial nerve sacrifice or extracapsular spread. There was no association between ERBB2 positivity and survival and no difference in survival between patients receiving radiation therapy vs radiation therapy plus chemotherapy. No patients had recurrence or distant metastasis after 5 disease-free years. CONCLUSIONS AND RELEVANCE:Salivary duct carcinoma is an aggressive disease. A large number of cases in this review were carcinoma ex pleomorphic adenoma and had classic negative prognostic indicators, such as perineural invasion, vascular invasion, and extracapsular spread. ERBB2 positivity was not associated with any difference in survival. Facial nerve involvement appears to indicate worse prognosis, as does nodal stage higher than N1. Recurrence and metastasis after 5 years are rare.

OBJECTIVE:To perform the translation, cross-cultural adaptation, and validation of the Sino-Nasal Outcome Test-22 (SNOT-22) questionnaire to the Hebrew language. STUDY DESIGN AND SETTING:A single-center prospective cross-sectional study. SUBJECTS AND METHODS:Seventy-three chronic rhinosinusitis (CRS) patients and 73 patients without sinonasal disease filled the Hebrew version of the SNOT-22 questionnaire. Fifty-one CRS patients underwent endoscopic sinus surgery, out of which 28 filled a postoperative questionnaire. Seventy-three healthy volunteers without sinonasal disease also answered the questionnaire. Internal consistency, test-retest reproducibility, validity, and responsiveness of the questionnaire were evaluated. RESULTS:Questionnaire reliability was excellent, with a high internal consistency (Cronbach's alpha coefficient, 0.91-0.936) and test-retest reproducibility (Spearman's coefficient, 0.962). Mean scores for the preoperative, postoperative, and control groups were 50.44, 29.64, and 13.15, respectively (P < .0001 for CRS vs controls, P < .001 for preoperative vs postoperative), showing validity and responsiveness of the questionnaire. CONCLUSION:The Hebrew version of SNOT-22 questionnaire is a valid outcome measure for patients with CRS with or without nasal polyps.

OBJECTIVES: Although it has been shown previously that changes in temporal coding produce changes in pitch in all cochlear regions, research has suggested that temporal coding might be best encoded in relatively apical locations. The authors hypothesized that although temporal coding may provide useable information at any cochlear location, low rates of stimulation might provide better sound quality in apical regions that are more likely to encode temporal information in the normal ear. In the present study, sound qualities of single electrode pulse trains were scaled to provide insight into the combined effects of cochlear location and stimulation rate on sound quality. DESIGN: Ten long-term users of MED-EL cochlear implants with 31-mm electrode arrays (Standard or FLEX) were asked to scale the sound quality of single electrode pulse trains in terms of how "Clean," "Noisy," "High," and "Annoying" they sounded. Pulse trains were presented on most electrodes between 1 and 12 representing the entire range of the long electrode array at stimulation rates of 100, 150, 200, 400, or 1500 pulses per second. RESULTS: Although high rates of stimulation are scaled as having a Clean sound quality across the entire array, only the most apical electrodes (typically 1 through 3) were considered Clean at low rates. Low rates on electrodes 6 through 12 were not rated as Clean, whereas the low-rate quality of electrodes 4 and 5 were typically in between. Scaling of Noisy responses provided an approximately inverse pattern as Clean responses. High responses show the trade-off between rate and place of stimulation on pitch. Because High responses did not correlate with Clean responses, subjects were not rating sound quality based on pitch. CONCLUSIONS: If explicit temporal coding is to be provided in a cochlear implant, it is likely to sound better when provided apically. In addition, the finding that low rates sound clean only at apical places of stimulation is consistent with previous findings that a change in rate of stimulation corresponds to an equivalent change in perceived pitch at apical locations. Collectively, the data strongly suggest that temporal coding with a cochlear implant is optimally provided by electrodes placed well into the second cochlear turn.

Treatment for intracranial germ cell tumors includes platinum-based chemotherapy and external beam radiation therapy, which are risk factors for hearing loss. In patients who experience significant sensorineural ototoxicity due to cochlear hair cell injury, dose reduction of chemotherapy may be necessary. This report describes an adolescent male, with excellent treatment response for an intracranial nongerminomatous germ cell tumor, who developed sensorineural hearing loss, which was central rather than cochlear in origin and unrelated to carboplatin. This patient highlights the need to carefully differentiate the type and etiology of sensorineural hearing loss in patients with brain tumors receiving ototoxic chemotherapy.