Faculty Bibliography

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.

BACKGROUND:A current challenge in osteoporosis is identifying patients at risk of bone fracture. PURPOSE/OBJECTIVE:To identify the machine learning classifiers that predict best osteoporotic bone fractures and, from the data, to highlight the imaging features and the anatomical regions that contribute most to prediction performance. STUDY TYPE/METHODS:Prospective (cross-sectional) case-control study. POPULATION/METHODS:. Field Strength/ Sequence: 3D FLASH at 3T. ASSESSMENT/RESULTS:Quantitative MRI outcomes by software algorithms. Mechanical and topological microstructural parameters of the trabecular bone were calculated for five femoral regions, and added to the vector of features together with bone mineral density measurement, fracture risk assessment tool (FRAX) score, and personal characteristics such as age, weight, and height. We fitted 15 classifiers using 200 randomized cross-validation datasets. Statistical Tests: Data: Kolmogorov-Smirnov test for normality. Model Performance: sensitivity, specificity, precision, accuracy, F1-test, receiver operating characteristic curve (ROC). Two-sided t-test, with P < 0.05 for statistical significance. RESULTS:The top three performing classifiers are RUS-boosted trees (in particular, performing best with head data, F1 = 0.64 ± 0.03), the logistic regression and the linear discriminant (both best with trochanteric datasets, F1 = 0.65 ± 0.03 and F1 = 0.67 ± 0.03, respectively). A permutation of these classifiers comprised the best three performers for four out of five anatomical datasets. After averaging across all the anatomical datasets, the score for the best performer, the boosted trees, was F1 = 0.63 ± 0.03 for All-features dataset, F1 = 0.52 ± 0.05 for the no-MRI dataset, and F1 = 0.48 ± 0.06 for the no-FRAX dataset. Data Conclusion: Of many classifiers, the RUS-boosted trees, the logistic regression, and the linear discriminant are best for predicting osteoporotic fracture. Both MRI and FRAX independently add value in identifying osteoporotic fractures. The femoral head, greater trochanter, and inter-trochanter anatomical regions within the proximal femur yielded better F1-scores for the best three classifiers. LEVEL OF EVIDENCE/METHODS:2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Tumors arising in the pineal region comprise a spectrum of different entities with distinct clinical and histopathological characteristics. Pineocytoma (PC), pineal parenchymal tumors of intermediate differentiation (PPTID) and papillary tumors of the pineal region (PTPR) mainly occur in adult patients and are low to moderately aggressive neoplasms (WHO degreeI-III). In contrast, pineoblastoma (PB) are high-grade (WHO degreeIV) malignancies primarily affecting children and adolescents. Especially for patients with unresectable or metastatic disease or at very young age survival outcomes remain poor despite aggressive multimodal treatment regimen. To date, no therapeutically actionable molecular targets have been identified. A subset of PB occur in patients with cancer predisposition syndromes including DICER1 and RB1 germline mutations, the latter in the context of trilateral retinoblastoma (TLRB). We analyzed a cohort of ~230 pineal tumors of different histologies using genome-wide DNA methylation profling and copy-number analysis, as well as gene panel sequencing, miRNA sequencing and gene expression profling. Unsupervised clustering based on DNA methyla-tion profiles revealed clear separation of known histopathological entities (PC, PTPR, PPTID) and, furthermore, distinction of subclasses within these groups. Interestingly, several biologically discrete subgroups emerged within the group of histologically diagnosed PBs or pineal primitive embryonal tu-mors/PNETs, which displayed distinct clinical associations (e.g. age distribution). RB1 alterations were recurrent in a small subgroup (PB-RB) including TLRBs as well as sporadic PB cases (~60%) showing similarities with retino-blastoma. About 45% of cases in the largest PB subgroup (PB-B) harbored alterations within the miRNA processing pathway (affecting DROSHA, DGCR8 or DICER1) suggesting a central role of altered miRNA biogenesis in the development of this group which showed evidence for global reduction of mature miRNA by miRNA-Seq. With this study, we provide a foundation for further clinical, molecular and functional characterization of PB subgroups

Objectives/UNASSIGNED:To perform a needs-based assessment for tracheostomy care education for nonsurgical first responders in the hospital setting and to implement and assess the efficacy of a targeted tracheostomy educational program. Methods/UNASSIGNED:A prospective observational study conducted between October 2017 and May 2018 including emergency medicine (EM) residents, internal medicine (IM) residents, and intensive care unit (ICU) advanced practice providers at 2 tertiary hospitals. Needs-based assessments were conducted, leading to specialty specific curricula. One-hour educational sessions included didactics and case-based simulation. A pre- and posttest objective knowledge quiz and self-assessment were administered, and a posttest was repeated at 6 months. Results/UNASSIGNED:< .05) in mean objective knowledge score was seen across all groups between pre- and postintervention assessments with relative but not significant improvement at 6 months. There were significant increases in comfort level from pre- to postintervention. At 6-month follow-up, comfort level remained significantly increased for the majority of questions for the EM group and for select questions for IM and ICU advanced practice provider groups. Discussion/UNASSIGNED:Nonsurgeons are often first responders to critical airway situations yet receive limited formal education regarding tracheostomy. We demonstrated improvement in knowledge and comfort after a targeted educational module for tracheostomy care and management. Implications for Practice/UNASSIGNED:Although tracheostomy care is multidisciplinary, specialty-specific education may provide a more relevant foundation on which to build skills. Prompt and effective management of tracheostomy emergencies by first responders may improve patient safety and reduce mortality.

Oropharyngeal carcinoma associated with the human papillomavirus is increasing in incidence and represents a unique head and neck disease with favorable treatment outcomes. This review evaluates the evolving role of radiotherapy in regional management with an overall goal of treatment de-escalation in the appropriate patient. Determining the optimal approach and selection factors for treatment de-escalation is under active investigation. Response to induction chemotherapy, refining adverse pathologic factors after a primary surgical approach, decreasing radiation dose with or without chemotherapy in the definitive or adjuvant settings as well as more selective nodal level irradiation all are current strategies for treatment de-escalation. This review details the likely changes in regional radiotherapy management for oropharyngeal carcinoma in the modern human papillomavirus era and discusses future approaches to patient selection with the goal of reducing toxicities while maintaining function preservation and quality of life in group of patients who are younger and healthier than traditional head and neck cancer patients.

Intralabyrinthine schwannomas (ILS) are rare tumors that frequently cause sensorineural hearing loss. The development and increased use of magnetic resonance imaging in recent years have facilitated the diagnosis of these tumors that present with otherwise nondiscriminant symptoms such as tinnitus, vertigo, and hearing loss. The following is a review of the presentation, pathophysiology, imaging, and treatment with a focused discussion on auditory rehabilitation options of ILS.