Faculty Bibliography

Both spatial and temporal cues determine the fate of immature neurons. A major challenge at the interface of developmental and systems neuroscience is to relate this spatiotemporal trajectory of maturation to circuit-level functional organization. This study examined the development of two extraocular motor nuclei (nIII and nIV), structures in which a motoneuron's identity, or choice of muscle partner, defines its behavioral role. We used retro-orbital dye fills, in combination with fluorescent markers for motoneuron location and birthdate, to probe spatial and temporal organization of the oculomotor (nIII) and trochlear (nIV) nuclei in the larval zebrafish. We describe a dorsoventral organization of the four nIII motoneuron pools, in which inferior and medial rectus motoneurons occupy dorsal nIII, while inferior oblique and superior rectus motoneurons occupy distinct divisions of ventral nIII. Dorsal nIII motoneurons are, moreover, born before motoneurons of ventral nIII and nIV. The order of neurogenesis can therefore account for the dorsoventral organization of nIII and may play a primary role in determining motoneuron identity. We propose that the temporal development of extraocular motoneurons plays a key role in assembling a functional oculomotor circuit. J. Comp. Neurol. 525:65-78, 2017. (c) 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

OBJECTIVES/HYPOTHESIS: Inhalation injury significantly increases morbidity and mortality in burn patients. Approximately one in five burn patients have acute injury to the larynx, trachea, and/or lungs-and as many as 70% have long-term laryngeal abnormalities. Although inhalation injury to the lung has been studied extensively, no models exist to study these insults to the larynx. As such, we developed an in vivo rabbit model to create precise and reproducible laryngeal burn with resultant tissue damage as a foundation for interventional studies. METHODS: Following tubeless tracheotomy, a custom temperature-control device was employed to apply heated air (70 degrees C-80 degrees C, 150 degrees C-160 degrees C, or 310 degrees C-320 degrees C) +/- smoke derived from unbleached cotton to the larynx, endoscopically, minimizing adjacent tissue damage in six rabbits. Pain, nutrition, and level of activity were monitored. Direct laryngoscopy and histological examination were performed 24 hours following insult. RESULTS: All animals survived injury with appropriate pain control; oral intake was initiated and all were adequately ventilating via tracheostomy. Burn sequelae were noted under direct visualization 24 hours after injury, and graded levels of edema and tissue damage were observed as a function of temperature. Edema obstructed true vocal fold visualization at increased temperatures. These injury patterns correlated with graded tissue damage on histology. CONCLUSION: We created an in vivo model of laryngeal burn injury employing a custom burn device resulting in graded tissue injury. This model is critical for investigation of the mechanisms underlying burn injury, and ultimately, the development and evaluation of therapies for this challenging population. LEVEL OF EVIDENCE: N/A. Laryngoscope, 2016.

Physical features of sensory stimuli are fixed, but sensory perception is context dependent. The precise mechanisms that govern contextual modulation remain unknown. Here, we trained mice to switch between two contexts: passively listening to pure tones and performing a recognition task for the same stimuli. Two-photon imaging showed that many excitatory neurons in auditory cortex were suppressed during behavior, while some cells became more active. Whole-cell recordings showed that excitatory inputs were affected only modestly by context, but inhibition was more sensitive, with PV+, SOM+, and VIP+ interneurons balancing inhibition and disinhibition within the network. Cholinergic modulation was involved in context switching, with cholinergic axons increasing activity during behavior and directly depolarizing inhibitory cells. Network modeling captured these findings, but only when modulation coincidently drove all three interneuron subtypes, ruling out either inhibition or disinhibition alone as sole mechanism for active engagement. Parallel processing of cholinergic modulation by cortical interneurons therefore enables context-dependent behavior.

OBJECTIVES/HYPOTHESIS:The aim of this study was to evaluate factors raised in malpractice litigation related to the diagnosis and management of melanoma and to further assess issues impacting outcome. STUDY DESIGN:Retrospective chart review. METHODS:The Westlaw legal database was searched for malpractice litigation resolved over the last 20 years relating to melanoma. Cases were evaluated for allegations, defendant specialty, outcome, and other issues raised. RESULTS:Of the 80 cases evaluated, 49% were resolved in the defendants' favor. In greater than 80% of cases, there was alleged misdiagnosis. In 35% of cases, the patient had expired secondary to melanoma at the time of litigation. There was no statistical difference in payments upon comparison of cases with and without mortality. A greater proportion of cases with dermatologists and pathologists as defendants involved alleged misdiagnosis. The most common locations for melanoma were the extremities and the head-and-neck region, at 32.5% and 22.5%, respectively. Location did not significantly impact the outcome of cases. CONCLUSION:Malpractice litigation relating to melanoma involves numerous physicians, including dermatologists, pathologists, and otolaryngologists. Alleged misdiagnosis of a pigmented lesion was the most common cause of litigation and involved physicians from numerous specialties. Patients who were misdiagnosed had a significantly higher likelihood of having active disease at the time of litigation. Ultimately improved methods of detecting concerning pigmented lesions need to be developed. Factors such as death and poor cosmetic outcome did not significantly impact litigation outcome. LEVEL OF EVIDENCE:NA Laryngoscope, 127:134-139, 2017.

OBJECTIVES/HYPOTHESIS: Mesenchymal stem cells (MSCs) hold therapeutic promise for vocal fold scar, yet the precise mechanism(s) underlying tissue level changes remain unclear. We hypothesize that MSCs interact with native fibroblasts to favorably affect healing. Furthermore, we hypothesize that these interactions vary based on MSC source. METHODS: Vocal fold fibroblasts (VFFs), adipose-derived stem cells, and bone marrow-derived stem cells (BMSCs) were extracted from Sprague-Dawley rats; and a coculture model was employed culturing VFFs +/- transforming growth factor (TGF-beta1) (10 ng/mL) +/- MSCs. Monoculture MSCs were also prepared as a control. Both extracellular matrix (ECM) and components of the TGF-beta signaling pathway were analyzed via polymerase chain reaction and western blotting. RESULTS: Significantly decreased TGF-beta1 mRNA and alpha-smooth muscle actin protein was observed in VFFs in response to TGF-beta1 in the coculture with both MSCs (P < 0.05, P < 0.01). BMSCs significantly downregulated collagen I (P < 0.05), collagen III (P < 0.05), Smad3 (P < 0.01), and TGF-beta1 receptor I (P < 0.01) mRNA in VFFs. Hyaluronic synthase-1 and 2 increased in cocultured BMSCs when compared with monocultured BMSCs at baseline and in response to TGF-beta1 (P < 0.01). CONCLUSION: MSCs had a favorable effect on ECM regulation as well as suppression of TGF-beta1 signaling in VFF. Bidirectional paracrine signaling was also observed as VFFs altered ECM regulation in MSCs. These data provide insight into the regenerative effects of MSCs and provide a foundation for clinical application. LEVEL OF EVIDENCE: N/A. Laryngoscope, 2016.

OBJECTIVES/OBJECTIVE:Pediatric rhinoplasty has traditionally raised numerous concerns, including its impact on growth as well as the psychological sequelae of undergoing a potentially appearance-altering procedure. Our objective was to critically evaluate available individual patient data relevant to pediatric rhinoplasty, and further discuss perioperative considerations. METHODS:A systematic review was conducted using PubMed/MEDLINE databases. Data extracted and analyzed from included studies included patient demographics, surgical indications, operative approaches, outcomes, complications, revision rates, and other clinical considerations. RESULTS:Seven studies encompassing 253 patients were included, with age ranging from 7 months to 19 years. Two-thirds of patients were male. 41.7% reported antecedent trauma, and common overall surgical indications included "functional aesthetic" (24.5%) followed by cleft lip nasal deformity (15.8%). The majority (79.1%) underwent open approaches, and 71.1% of patients underwent concomitant septal intervention. The most frequently used grafting materials were septal cartilage (52.8%) and conchal cartilage (16.5%). Surgical outcomes were heterogeneous among these studies. Complication rates were only specified in 5 of the 7 studies and totaled 57 patients (39.6%). Aesthetic dissatisfaction (11.8%) and postoperative nasal obstruction (5.6%) were the most commonly reported complications. Revisions were performed in 13.5%. CONCLUSION/CONCLUSIONS:Rhinoplasty is safe in the pediatric population, although revisions rates appear greater than those reported in adults. This study of 253 represents the largest pooled sample size to date; nonetheless, non-standardized outcome measures, minimal long-term followup data, and lack of discussion regarding psychological sequelae all contribute to the need for further high-quality studies evaluating this topic.

BACKGROUND: Proficiency with common endocrine operations is expected of graduating, general surgery residents. However, no expert consensus guidelines exist about these expectations. METHODS: Members of the American Association of Endocrine Surgeons were surveyed about their opinions on resident proficiency with common endocrine operations. RESULTS: Overall response rate was 38%. A total of 92% of the respondents operate with residents. On average, they believed that the steps of a total thyroidectomy for benign disease and a well-localized parathyroidectomy could be performed by a postgraduate year 4 surgery resident. Specific steps that they thought might require more training included decisions to divide the strap muscles or leaving a drain. Approximately 66% of respondents thought that a postgraduate year 5 surgery resident could independently perform a total thyroidectomy for benign disease, but only 45% felt similarly for malignant thyroid disease; 79% thought that a postgraduate year 5 surgery resident could independently perform a parathyroidectomy. Respondents' years of experience correlated with their opinions about resident autonomy for total thyroidectomy (benign r = 0.38, P < .001; malignant r = 0.29, P = .001) but not parathyroidectomy. On multivariate analysis, sex and years of experience of the respondents were independently associated with opinions on autonomy but only for total thyroidectomy for benign disease (P = .001). Annual endocrine volume of the respondents did not correlate with beliefs in autonomy. CONCLUSION: There was general agreement among responding members of the AAES about resident proficiency and autonomy with common endocrine operations. As postgraduate year 5 residents may not be proficient in advanced endocrine operations, opportunities exist to improve training prior to the transition to independent practice for graduates that anticipate performing endocrine operations routinely.

OBJECTIVES/HYPOTHESIS: In response to concerns regarding physician-industry relationships, the Physician Sunshine Act of 2010 was passed in an effort to increase transparency and accountability. Our objective was to determine whether there is an association between industry support and scholarly impact among academic otolaryngologists. METHODS: Faculty listings, academic rank, and fellowship training of academic otolaryngologists were accessed from departmental websites. H-indices, number of publications, and publication range (years) of each individual were calculated using the Scopus database. The Center for Medicare and Medicaid Services Open Payments database was used to determine industry payments during 2014 to each otolaryngologist. RESULTS: Of 1,515 otolaryngologists, 65.4% received industry support and 15.8% received support > $1,000. No difference in impact, as measured by the h-index, was noted upon comparison of those receiving support and those who did not (P > 0.05). Individuals receiving > $1,000 had higher h-indices and total publications than those receiving < $1,000 or receiving no support (H = 17.8 vs. 10.9, P < 0.0001), even upon controlling for academic seniority. Upon organization by subspecialty, individuals receiving > $1,000 had greater scholarly impact among most subspecialties. Industry contributions increased with advancing experience. CONCLUSION: Receiving industry contributions greater than $1,000 is associated with greater scholarly impact among academic otolaryngologists. In a smaller surgical specialty, such as otolaryngology-head and neck surgery, direct industry research support-as well as indirect contributions through the support of educational programs, consulting, and other expenses-potentially impacts scholarly discourse; these findings do not reflect a causal relationship and may require further characterization. LEVEL OF EVIDENCE: N/A. Laryngoscope, 2016.