Faculty Bibliography

Long non-coding RNAs (lncRNA) modulate gene expression at the epigenetic, transcriptional and post-transcriptional levels and are involved in tumorigenesis. They can form complex secondary and tertiary structures and have been shown to act as precursors, enhancers, reservoirs and decoys in the complex endogenous RNA network. They were first reported in relation to oral squamous cell carcinoma (OSCC) in 2013. Here, we summarise the functional roles and pathways of the most commonly studied lncRNAs in OSCC. Existing research demonstrates the involvement of lncRNA within pivotal pathways leading to the development and spread of OSCC, including interactions with key cancer-associated microRNAs such as miR-21. The number of studies on lncRNA and OSCC remains limited in this new field. As evidence grows, the tissue-specific expression patterns of lncRNAs should further advance our understanding of the altered regulatory networks in OSCC and possibly reveal new biomarkers and therapeutic targets.

BACKGROUND:Long non-coding RNAs (lncRNAs) have important roles in regulating gene expression pertaining to cell proliferation, survival, migration and genomic stability. Dysregulated expression of lncRNAs is implicated in cancer initiation, progression and metastasis. OBJECTIVES/OBJECTIVE:To explore, map and summarize the extent of evidence from clinical studies investigating the differential expression of lncRNAs in oral/tongue squamous cell carcinoma. METHODS:PubMed, Scopus and Web of Science were used as search engines. Clinical, full-length, English language studies were included. PRISMA-ScR protocol was used to evaluate and present results. The present scoping review summarizes relationships of the differential expression of lncRNAs with the presence of tumour and with clinicopathological features including survival. RESULTS:Almost half of the investigated transcripts have been explored in more than one study, yet not always with consistent results. The collected data were also compared to the limited studies investigating oral epithelial dysplasia. Data are not easily comparable, first because of different methods used to define what differential expression is, and second because only a limited number of studies performed multivariate analyses to identify clinicopathological features associated with the differentially expressed lncRNAs. CONCLUSIONS:Standard methods and more appropriate data analyses are needed in order to achieve reliable results from future studies.

Although modern cochlear implants (CIs) use cathodic-leading symmetrical biphasic pulses to stimulate the auditory nerve, a growing body of evidence suggests that anodic-leading pulses may be more effective. The positive polarity has been shown to produce larger electrically evoked compound action potential (ECAP) amplitudes, steeper slope of the amplitude growth function, and broader spread of excitation (SOE) patterns. Polarity has also been shown to influence pitch perception. It remains unclear how polarity affects the relation between physiological SOE and psychophysical pitch perception. Using a within-subject design, we examined the correlation between performance on a pitch-ranking task and spatial separation between SOE patterns for anodic and cathodic-leading symmetric biphasic pulses for 14 CI ears. Overall, there was no effect of polarity on either ECAP SOE patterns, pitch ranking performance, or the relation between the two. This result is likely due the use of symmetric biphasic pulses, which may have reduced the size of the effect previously observed for pseudomonophasic pulses. Further research is needed to determine if a pseudomonophasic stimulus might further improve the relation between physiology and pitch perception.

Purpose: Non-tuberculous mycobacteria (NTM) can cause clinically significant lung disease and frequent pneumonias. It is unknown whether impaired swallowing contributes to the pathophysiology of NTM. Patients with NTM may exhibit decreased airway protection. Our aim is to determine airway protection and bolus clearance in patients with NTM. Method(s): Videofluoroscopy (VF) was prospectively collected from 98 patients with NTM (67 female; ages 33-88). Two boluses of 3,5,10 ml thin liquid, two 5 cc puree Varibar, cracker were analyzed per subject (N = 980 swallows).Outcome measures included Penetration/Aspiration Scale (PAS) and ordinal ratings of residue in the valleculae and pyriform sinuses. Worst PAS scores categorized subject as unsafe (C 3) or safe (B 2). The correlation between clinical information and the present of penetration/aspiration and pharyngeal residue structures was analyzed. Result(s): Inter-and intra-rater reliability of PAS ratings were assessed using two-way mixed intraclass correlation coefficients (ICC) on 20% of the data with excellent results (intra-rater: ICC 0.98, 95% CI 0.95-0.98 and inter-rater: ICC 0.85, 95% CI 0.69-0.92). The proportion of impaired swallows in the whole dataset was 12.9% (127/980 swallows with PAS scores C 3). There was no correlation between presence of penetration/aspiration and pharyngeal residue with productive cough, pneumonia, smoking history and presence of acid reflux. Conclusions (Including Clinical Relevance): Patients with NTM appear to have impaired swallow function as represented by impaired airway protection. Future work should explore swallowing physiology compared to a control group

PURPOSE/OBJECTIVE:To evaluate percutaneous dilatational tracheostomy in patients ≥ 85 years old: its complication rate and possible risk factors. In addition, to assess prognostic factors for short, intermediate and long term survival following the procedure. METHODS:A retrospective case-control study of 72 patients ≥ 85 years who received percutaneous dilatation tracheotomy (PTD), compared to a control group of younger patients (n = 182). Demographics, clinical and laboratory data were collected. Survival and risk for complications were analyzed. RESULTS:The study group's mean age was 89 ± 4. Twelve patients had complications, three (4.2%) were major. No significant difference was found in overall complication rates between the groups. Cerebrovascular disease with neurologic deficits and pre-procedure albumin levels were significantly associated with complications. Survival rates did not differ in 1 week and 1 month following procedure between study and control group. There was a significant difference in the 1-year survival rates between the patients ≥ 85 years and the control groups (18.1% vs. 34.4%, p = 0.01, respectively). Congestive heart failure, a frailty score > 0.27 and failure to wean from a cannula were associated with reduced 1-year survival. CONCLUSION/CONCLUSIONS:PTD is safe for patients ≥ 85 years. Complication risk factors and reduced survival should be discussed with patients and families before conducting tracheostomies. LEVEL OF EVIDENCE/METHODS:3b.

OBJECTIVES:The purpose of this study was to obtain an electrophysiological analog of masking release using speech-evoked cortical potentials in steady and modulated maskers and to relate this masking release to behavioral measures for the same stimuli. The hypothesis was that the evoked potentials can be tracked to a lower stimulus level in a modulated masker than in a steady masker and that the magnitude of this electrophysiological masking release is of the same order as that of the behavioral masking release for the same stimuli. DESIGN:Cortical potentials evoked by an 80-ms /ba/ stimulus were measured in two steady maskers (30 and 65 dB SPL), and in a masker that modulated between these two levels at a rate of 25 Hz. In each masker, a level series was undertaken to determine electrophysiological threshold. Behavioral detection thresholds were determined in the same maskers using an adaptive tracking procedure. Masking release was defined as the difference between signal thresholds measured in the steady 65-dB SPL masker and the modulated masker. A total of 23 normal-hearing adults participated. RESULTS:Electrophysiological thresholds were uniformly elevated relative to behavioral thresholds by about 6.5 dB. However, the magnitude of masking release was about 13.5 dB for both measurement domains. CONCLUSIONS:Electrophysiological measures of masking release using speech-evoked cortical auditory evoked potentials correspond closely to behavioral estimates for the same stimuli. This suggests that objective measures based on electrophysiological techniques can be used to reliably gauge aspects of temporal processing ability.

OBJECTIVES/OBJECTIVE:The medial sural artery perforator (MSAP) free flap is an uncommonly utilized soft tissue flap in head and neck reconstruction. It is a thin, pliable, fasciocutaneous flap that provides significant pedicle length. The donor site can be closed primarily, and its location is more aesthetically pleasing to patients. We aim to describe the MSAP flap and compare it to other commonly used free flaps in the head and neck. STUDY DESIGN/METHODS:Retrospective case series. METHODS:A retrospective review of all MSAP cases performed at New York University Langone Health was performed from July 2016 to November 2017. We examined the patients' age, diagnosis, history of prior radiation therapy, and comorbidities, as well as flap-specific information and recipient site. RESULTS:(15 cm × 8 cm). The flaps ranged from 5 to 12 mm in thickness. Venous coupler size ranged from 2.0 to 3.5 mm. Primary closure of the donor site was achieved in 18 of 21 flaps. Twenty of 21 flaps were transferred successfully. CONCLUSION/CONCLUSIONS:The MSAP flap is a highly versatile and reliable option for a thin, pliable soft tissue flap with a donor site that may be preferable over the radial forearm free flap and anterolateral thigh flap in complex head and neck reconstruction. LEVEL OF EVIDENCE/METHODS:4. Laryngoscope, 2018.

Purpose: The purpose of this study is to quantify interfractional dosimetric variations in radiotherapy of oropharyngeal cancer and investigate the application of statistical process control (SPC) to determine significantly deviated fractions for management.
Method(s): Thirteen oropharyngeal cancer patients treated by IMRT or VMAT with daily CBCT were retrospectively reviewed. CBCT images of every other fraction were imported to the software Velocity and registered to planning CT using the 6DOF couch shifts generated during patient setup. Using Velocity Adaptive Monitoring module, the setup-corrected CBCT was matched to planning CT using a deformable registration. The module also generated dose volume histograms (DVHs) at each CBCT from planning doses for the deformed plan structure sets. Volumes and dose metrics at each fraction were calculated and rated with plan values to evaluate interfractional dosimetric variations using a SPC framework. T-tests between plan and fraction volumes were performed to find statistically insignificant fractions. Average, upper and lower process capacity limits (UCL, LCL) of each dose metric were derived from these fractions using conventional SPC guidelines.
Result(s): GTV and OAR volumes in first 13 fractions had no significantly changes from the plan, subsequently reduced by 10% to treatment completion, except oral cavity. There were 3%-4% increases in parotid mean doses, but no significant differences in dose metrics of GTVand other OARs. The changes were organ and patient dependent. Control charts for various dose metrics were generated to assess the metrics for individual patient. The occurrences of one or several dose metrics out of the control limits warrant immediate investigation of the fraction.
Conclusion(s): Daily CBCT could be used to monitor dosimetric variations of targets and OARs resulting from volume changes and tissue deformation in oropharyngeal cancer radiotherapy. Treatment review with guidance of a SPC tool may enable objectively and consistently identify significantly deviated fractions