Faculty Bibliography

The orbit is contained within a complex bony architecture with overlying soft tissue that involves many important anatomical structures. Orbital trauma is a frequent cause of damage to these structures. The authors review the literature on reconstructive techniques focusing on fractures of the orbital rim, orbital roof, orbital floor, medial orbital wall, and naso-orbito-ethmoid complex. A thorough literature review was conducted using PubMed analyzing articles relevant to the subject matter. Various search terms were used to identify articles regarding orbital trauma presentation, diagnosis, management, as well as postoperative complications. Articles were examined by all authors and pertinent information was gleaned for the purpose of generating this review. Orbital trauma can result in a wide variety of complications in form and function. Not all orbital fractures require operative repair. However, bony disruption can cause enophthalmos, hypophthalmos, telecanthus, epiphora, cerebrospinal fluid leaks, orbital hematoma, and even blindness to name a few. Timing of operative repair as well as reconstructive method is dictated by the patient's individual presentation. Successful fracture management requires a detailed understanding of the anatomy and pathophysiology to ensure restoration of the patients' preoperative state. Orbital trauma encompasses a wide variety of mechanisms of injury and resulting fracture patterns. A variety of surgical approaches to the orbit exist as has been discussed allowing the surgeon access to all area of interest. Regardless of the fracture complexity, the principles of atraumatic technique, anatomic reduction, and stable fixation apply in all cases.

OBJECTIVES/OBJECTIVE:(1) To determine the effect of hearing aid (HA) bandwidth on bimodal speech perception in a group of unilateral cochlear implant (CI) patients with diverse degrees and configurations of hearing loss in the nonimplanted ear, (2) to determine whether there are demographic and audiometric characteristics that would help to determine the appropriate HA bandwidth for a bimodal patient. DESIGN/METHODS:Participants were 33 experienced bimodal device users with postlingual hearing loss. Twenty three of them had better speech perception with the CI than the HA (CI>HA group) and 10 had better speech perception with the HA than the CI (HA>CI group). Word recognition in sentences (AzBio sentences at +10 dB signal to noise ratio presented at 0° azimuth) and in isolation [CNC (consonant-nucleus-consonant) words] was measured in unimodal conditions [CI alone or HAWB, which indicates HA alone in the wideband (WB) condition] and in bimodal conditions (BMWB, BM2k, BM1k, and BM500) as the bandwidth of an actual HA was reduced from WB to 2 kHz, 1 kHz, and 500 Hz. Linear mixed-effect modeling was used to quantify the relationship between speech recognition and listening condition and to assess how audiometric or demographic covariates might influence this relationship in each group. RESULTS:For the CI>HA group, AzBio scores were significantly higher (on average) in all bimodal conditions than in the best unimodal condition (CI alone) and were highest at the BMWB condition. For CNC scores, on the other hand, there was no significant improvement over the CI-alone condition in any of the bimodal conditions. The opposite pattern was observed in the HA>CI group. CNC word scores were significantly higher in the BM2k and BMWB conditions than in the best unimodal condition (HAWB), but none of the bimodal conditions were significantly better than the best unimodal condition for AzBio sentences (and some of the restricted bandwidth conditions were actually worse). Demographic covariates did not interact significantly with bimodal outcomes, but some of the audiometric variables did. For CI>HA participants with a flatter audiometric configuration and better mid-frequency hearing, bimodal AzBio scores were significantly higher than the CI-alone score with the WB setting (BMWB) but not with other bandwidths. In contrast, CI>HA participants with more steeply sloping hearing loss and poorer mid-frequency thresholds (≥82.5 dB) had significantly higher bimodal AzBio scores in all bimodal conditions, and the BMWB did not differ significantly from the restricted bandwidth conditions. HA>CI participants with mild low-frequency hearing loss showed the highest levels of bimodal improvement over the best unimodal condition on CNC words. They were also less affected by HA bandwidth reduction compared with HA>CI participants with poorer low-frequency thresholds. CONCLUSIONS:The pattern of bimodal performance as a function of the HA bandwidth was found to be consistent with the degree and configuration of hearing loss for both patients with CI>HA performance and for those with HA>CI performance. Our results support fitting the HA for all bimodal patients with the widest bandwidth consistent with effective audibility.

OBJECTIVE:To assess the impact of implementing a dedicated Patient Safety and Quality Improvement (PSQI) curriculum for otolaryngology residents. METHODS:Residents in two otolaryngology residency programs were recruited to participate in the study. Residents at institution A (intervention group) participated in a formal, newly developed, year-long PSQI curriculum. Residents at institution B (control group) participated in traditional, morbidity, and mortality conference-based PSQI education, with no formal curriculum in place. Curriculum participants completed anonymous surveys to assess learner satisfaction. Validated instruments were administered to assess for changes in resident confidence in the ability to develop PSQI projects, their attitudes toward patient safety, and PSQI-related knowledge. The number and quality of PSQI-related resident projects were also assessed. RESULTS:Survey responses demonstrated excellent learner satisfaction with the curriculum. Based on validated instrument-based responses, both programs demonstrated similar confidence scores (P = 0.05), safety attitudes (P = 0.82), and PSQI knowledge (P = 0.29) at the beginning of the year. The residents of institution A demonstrated significant improvement in confidence (P = 0.00009) and knowledge (P = 0.0006) after completing the curriculum, with no improvement noted for residents at institution B in either confidence (P = 0.06) or knowledge (P = 0.79). Neither program demonstrated improvement in attitudes toward patient safety at the end of the year-long curriculum. CONCLUSION/CONCLUSIONS:Implementing a formal curriculum dedicated to PSQI led to an improvement in PSQI-related project development confidence and PSQI knowledge. Attitudes toward safety did not improve over the course of a year. Longer-term studies involving multiple institutions and other interventions are needed to evaluate the impact and duration of changes that occur. LEVEL OF EVIDENCE/METHODS:1b. Laryngoscope, 2018.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Direct glucocorticoid (GC) injection for vocal fold (VF) scarring has evolved as a therapeutic strategy, but the mechanisms underlying the antifibrotic effects remain unclear. GCs act via the glucocorticoid receptor (GR), which is phosphorylated at multiple serine residues in a hormone-dependent manner to affect bioactivity. We hypothesize that GCs regulate SMAD signaling via GR phosphorylation in vocal fold fibroblasts (VFFs). STUDY DESIGN/METHODS:In vitro. METHODS:phosphorylation was examined via sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunocytochemistry. Quantitative polymerase chain reaction was employed to determine GR-mediated effects of DM on genes related to fibrosis. RESULTS:phosphorylation increased. RU486 limited the effects of DM. SMAD3 and SMAD7 mRNA expression significantly decreased 4 hours after DM administration (P < 0.05); this response was negated by RU486. COL1A1 remained unchanged, and ACTA2 significantly increased following 24 hours of DM treatment (P < 0.05). CONCLUSION/CONCLUSIONS:DM regulated TGF-β1 signaling via altered SMAD3 and SMAD7 expression. This response was associated with altered GR phosphorylation. These findings provide insight into the mechanisms of steroidal effects on vocal fold repair; ultimately, we seek to enhance therapeutic strategies for these challenging patients. LEVEL OF EVIDENCE/METHODS:NA. Laryngoscope, 2018.

BACKGROUND:Prompted by the revolution in high-throughput sequencing and its potential impact for treating cancer patients, we initiated a clinical research study to compare the ability of different sequencing assays and analysis methods to analyze glioblastoma tumors and generate real-time potential treatment options for physicians. METHODS:A consortium of seven institutions in New York City enrolled 30 patients with glioblastoma and performed tumor whole genome sequencing (WGS) and RNA sequencing (RNA-seq; collectively WGS/RNA-seq); 20 of these patients were also analyzed with independent targeted panel sequencing. We also compared results of expert manual annotations with those from an automated annotation system, Watson Genomic Analysis (WGA), to assess the reliability and time required to identify potentially relevant pharmacologic interventions. RESULTS:WGS/RNAseq identified more potentially actionable clinical results than targeted panels in 90% of cases, with an average of 16-fold more unique potentially actionable variants identified per individual; 84 clinically actionable calls were made using WGS/RNA-seq that were not identified by panels. Expert annotation and WGA had good agreement on identifying variants [mean sensitivity = 0.71, SD = 0.18 and positive predictive value (PPV) = 0.80, SD = 0.20] and drug targets when the same variants were called (mean sensitivity = 0.74, SD = 0.34 and PPV = 0.79, SD = 0.23) across patients. Clinicians used the information to modify their treatment plan 10% of the time. CONCLUSION/CONCLUSIONS:These results present the first comprehensive comparison of technical and machine augmented analysis of targeted panel and WGS/RNA-seq to identify potential cancer treatments.

OBJECTIVE:To determine adverse events after endoscopic flexible vs endoscopic rigid cricopharyngeal myotomy for treatment of Zenker's diverticulum (ZD). DATA SOURCES/METHODS:Systematic review of MEDLINE, Web of Science, CINAHL, Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials for all years according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Additional studies were identified from review citations and a by hand search of manuscripts referencing ZD. REVIEW METHODS/METHODS:A structured literature search was conducted to identify studies for this systematic review. Methodological Index for Non-randomized Studies (MINORS) criteria were applied to assess study quality. For inclusion, each study had to provide data for at least 10 adult patients who had undergone endoscopic ZD repair reporting clear association with the postprocedure course in each case. Data extracted included all reported adverse events, recurrences, follow-up, and operative times. RESULTS:In total, 115 studies were included. All but 8 were retrospective case series. Sixty-one reported series of patients after rigid endoscopic stapler repair, 31 after rigid laser repair, and 13 with other rigid endoscopic instruments. Twenty-nine flexible endoscopic studies were included. Mortality, infection, and perforation were not significantly more likely in either the rigid or the flexible group, but bleeding and recurrence were more likely after flexible endoscopic techniques (20% vs <10% and 4% vs 0%, respectively). Dental injury and vocal fold palsy were reported rarely in the rigid endoscopic groups. CONCLUSIONS:Adverse events are rare after endoscopic Zenker's repair. The flexible approach minimizes exposure limitations and can be completed in some patients without general anesthesia. Transoral rigid approaches result in fewer revision surgeries compared with flexible diverticulotomy.

Neural representations of the external world are constructed and updated in a manner that depends on behavioral context. For neocortical networks, this contextual information is relayed by a diverse range of neuromodulatory systems, which govern attention and signal the value of internal state variables such as arousal, motivation, and stress. Neuromodulators enable cortical circuits to differentially process specific stimuli and modify synaptic strengths in order to maintain short- or long-term memory traces of significant perceptual events and behavioral episodes. One of the most important subcortical neuromodulatory systems for attention and arousal is the noradrenergic locus coeruleus. Here we report that the noradrenergic system can enhance behavior in rats performing a self-initiated auditory recognition task, and optogenetic stimulation of noradrenergic locus coeruleus neurons accelerated the rate at which trained rats began correctly responding to a change in reward contingency. Animals successively progressed through distinct behavioral epochs, including periods of perseverance and exploration that occurred much more rapidly when animals received locus coeruleus stimulation. In parallel, we made recordings from primary auditory cortex and found that pairing tones with locus coeruleus stimulation led to a similar set of changes to cortical tuning profiles. Thus both behavioral and neural responses go through phases of adjustment for exploring and exploiting environmental reward contingencies. Furthermore, behavioral engagement does not necessarily recruit optimal locus coeruleus activity.

Skill learning is fundamental to the acquisition of many complex behaviors that emerge during development. For example, years of practice give rise to perceptual improvements that contribute to mature speech and language skills. While fully honed learning skills might be thought to offer an advantage during the juvenile period, the ability to learn actually continues to develop through childhood and adolescence, suggesting that the neural mechanisms that support skill learning are slow to mature. To address this issue, we asked whether the rate and magnitude of perceptual learning varies as a function of age as male and female gerbils trained on an auditory task. Adolescents displayed a slower rate of perceptual learning as compared to their young and mature counterparts. We recorded auditory cortical neuron activity from a subset of adolescent and adult gerbils as they underwent perceptual training. While training enhanced the sensitivity of most adult units, the sensitivity of many adolescent units remained unchanged, or even declined across training days. Therefore, the average rate of cortical improvement was significantly slower in adolescents as compared to adults. Both smaller differences between sound-evoked response magnitudes and greater trial-to-trial response fluctuations contributed to the poorer sensitivity of individual adolescent neurons. Together, these findings suggest that elevated sensory neural variability limits adolescent skill learning.Significance Statement:The ability to learn new skills emerges gradually as children age. This prolonged development, often lasting well into adolescence, suggests that children, teens, and adults may rely on distinct neural strategies to improve their sensory and motor capabilities. Here, we found that practice-based improvement on a sound detection task is slower in adolescent gerbils than in younger or older animals. Neural recordings made during training revealed that practice enhanced the sound sensitivity of adult cortical neurons, but had a weaker effect in adolescents. This latter finding was partially explained by the fact that adolescent neural responses were more variable than in adults. Our results suggest that one mechanistic basis of adult-like skill learning is a reduction in neural response variability.

Chronic inflammation of the salivary glands from pathologic conditions such as Sjögren's syndrome can result in glandular destruction and hyposalivation. To understand which molecular factors may play a role in clinical cases of salivary gland hypofunction, we developed an aquaporin 5 (AQP5) Cre mouse line to produce genetic recombination predominantly within the acinar cells of the glands. We then bred these mice with the TNF-αglo transgenic line to develop a mouse model with salivary gland-specific overexpression of TNF-α; which replicates conditions seen in sialadenitis, an inflammation of the salivary glands resulting from infection or autoimmune disorders such as Sjögren's syndrome. The resulting AQP5-Cre/TNF-αglo mice display severe inflammation in the salivary glands with acinar cell atrophy, fibrosis, and dilation of the ducts. AQP5 expression was reduced in the salivary glands, while tight junction integrity appeared to be disrupted. The immune dysregulation in the salivary gland of these mice led to hyposalivation and masticatory dysfunction.

Perineural invasion (PNI), the neoplastic invasion of nerves, is a common pathological finding in head and neck cancer that is associated with poor clinical outcomes. PNI is a histological finding of tumor cell infiltration and is distinct from perineural tumor spread (PNTS), which is macroscopic tumor involvement along a nerve extending from the primary tumor that is by definition more advanced, being radiologically or clinically apparent. Despite widespread acknowledgement of the prognostic significance of PNI/PNTS, the mechanisms underlying its pathogenesis remain largely unknown, and specific therapies targeting nerve invasion are lacking. The use of radiation therapy for PNI/PNTS can improve local control and reduce devastating failures at the skull base. However, the optimal volumes to be delineated with respect to targeting cranial nerve pathways are not well defined, and radiation may carry risks of major toxicity secondary to the location of adjacent critical structures. Here we examine the pathogenesis of these phenomena, analyze the role of radiation in PNI/PNTS, and propose guidelines for radiation treatment design based on the best available evidence and the authors' collective experience in order to advance understanding and therapy of this ominous cancer phenotype.