Faculty Bibliography
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Department/Unit:Otolaryngology
Total Results:
7803
Mandibular reconstruction
Mandibular reconstruction presents unique functional and aesthetic challenges to the reconstructive surgeon. This review will cover current techniques for mandibular reconstruction, including the various plating strategies for rigid fixation, the choice of osseous donor site, and the concurrent reconstruction of associated soft tissue defects. Recent developments and future horizons in mandibular reconstruction including the use of virtual surgical planning and tissue engineering will also be addressed.
PMID: 29362116
ISSN: 1879-0593
CID: 2988622
DNA methylation-based classification of central nervous system tumours
Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.
PMCID:6093218
PMID: 29539639
ISSN: 1476-4687
CID: 2992882
Development and Characterization of an In Vitro Model for Radiation-Induced Fibrosis
Radiation-induced fibrosis (RIF) is a major side effect of radiotherapy in cancer patients with no effective therapeutic options. RIF involves excess deposition and aberrant remodeling of the extracellular matrix (ECM) leading to stiffness in tissues and organ failure. Development of preclinical models of RIF is crucial to elucidate the molecular mechanisms regulating fibrosis and to develop therapeutic approaches. In addition to radiation, the main molecular perpetrators of fibrotic reactions are cytokines, including transforming growth factor-β (TGF-β). We hypothesized that human oral fibroblasts would develop an in vitro fibrotic reaction in response to radiation and TGF-β. We demonstrate here that fibroblasts exposed to radiation followed by TGF-β exhibit a fibrotic phenotype with increased collagen deposition, cell proliferation, migration and invasion. In this in vitro model of RIF (RIFiv), the early biological processes involved in fibrosis are demonstrated, along with increased levels of several molecules including collagen 1α1, collagen XIα1, integrin-α2 and cyclin D1 mRNA in irradiated cells. A clinically relevant antifibrotic agent, pentoxifylline, and a curcumin analogue both mitigated collagen deposition in irradiated fibroblast cultures. In summary, we have established an in vitro model for RIF that facilitates the elucidation of molecular mechanisms in radiation-induced fibrosis and the development of effective therapeutic approaches.
PMCID:5837959
PMID: 29351058
ISSN: 1938-5404
CID: 2988412
Workforce Considerations, Training, and Certification of Physicians in Europe
Following recent geopolitical events and unification of Europe, the European Union (EU) is currently confronted with health care workforce shortage and insufficient uniform access to quality care. Aging population, difficulties with physician retention, and mobility of health care professionals are thought to contribute to this problem. Because of the differences in medical education and residency curriculum across the European countries, there is a need for a standardized training and certification. Current government initiatives are geared toward developing common policies and programs across the EU countries to address health care access.
PMID: 29525389
ISSN: 1557-8259
CID: 2992422
Journal of the Association for Research in Otolaryngology : JARO. 2018:19(3):287-299.DOI: 10.1007/s10162-018-0658-8
Effect of Pulse Rate on Loudness Discrimination in Cochlear Implant Users
Stimulation pulse rate affects current amplitude discrimination by cochlear implant (CI) users, indicated by the evidence that the JND (just noticeable difference) in current amplitude delivered by a CI electrode becomes larger at higher pulse rates. However, it is not clearly understood whether pulse rate would affect discrimination of speech intensities presented acoustically to CI processors, or what the size of this effect might be. Intensity discrimination depends on two factors: the growth of loudness with increasing sound intensity and the loudness JND (or the just noticeable loudness increment). This study evaluated the hypothesis that stimulation pulse rate affects loudness JND. This was done by measuring current amplitude JNDs in an experiment design based on signal detection theory according to which loudness discrimination is related to internal noise (which is manifested by variability in loudness percept in response to repetitions of the same physical stimulus). Current amplitude JNDs were measured for equally loud pulse trains of 500 and 3000Â pps (pulses per second) by increasing the current amplitude of the target pulse train until it was perceived just louder than a same-rate or different-rate reference pulse train. The JND measures were obtained at two presentation levels. At the louder level, the current amplitude JNDs were affected by the rate of the reference pulse train in a way that was consistent with greater noise or variability in loudness perception for the higher pulse rate. The results suggest that increasing pulse rate from 500 to 3000Â pps can increase loudness JND by 60Â % at the upper portion of the dynamic range. This is equivalent to a 38Â % reduction in the number of discriminable steps for acoustic and speech intensities.
PMCID:5962473
PMID: 29532190
ISSN: 1438-7573
CID: 2992622
Programmed death ligand 1 expression and tumor infiltrating lymphocytes in neurofibromatosis type 1 and 2 associated tumors
Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) or its ligand (PD-L1) have been shown to be effective in treating patients with a variety of cancers. Biomarker studies have found positive associations between clinical response rates and PD-L1 expression on tumor cells, as well as the presence of tumor infiltrating lymphocytes (TILs). It is currently unknown whether tumors associated with neurofibromatosis types 1 and 2 (NF1 and NF2) express PD-L1. We performed immunohistochemistry for PD-L1 (clones SP142 and E1L3N), CD3, CD20, CD8, and CD68 in NF1-related tumors (ten dermal and six plexiform neurofibromas) and NF2-related tumors (ten meningiomas and ten schwannomas) using archival formalin-fixed paraffin-embedded tissues. Expression of PD-L1 was considered positive in cases with > 5% membranous staining of tumor cells, in accordance with previously published biomarker studies. PD-L1 expression in tumor cells (using the SP142 and E1L3N clones, respectively) was assessed as positive in plexiform neurofibromas (6/6 and 5/6) dermal neurofibromas (8/10 and 6/10), schwannomas (7/10 and 10/10), and meningiomas (4/10 and 2/10). Sparse to moderate presence of CD68, CD3, or CD8 positive TILs was found in 36 (100%) of tumor specimens. Our findings indicate that adaptive resistance to cell-mediated immunity may play a major role in the tumor immune microenvironment of NF1 and NF2-associated tumors. Expression of PD-L1 on tumor cells and the presence of TILs suggest that these tumors might be responsive to immunotherapy with immune checkpoint inhibitors, which should be explored in clinical trials for NF patients.
PMCID:5930071
PMID: 29427150
ISSN: 1573-7373
CID: 2969022
The impact of adjuvant chemoradiotherapy timing on survival of head and neck cancers
BACKGROUND:Delays in postoperative head and neck (HN) radiotherapy have been associated with decreased overall survival; however, the impact of delays in postoperative HN chemoradiotherapy remains undefined. METHODS:All patients with nonmetastatic HN cancer (oral cavity, oropharynx, larynx, hypopharynx) who underwent curative intent surgery and received adjuvant chemoradiotherapy were identified from the National Cancer Database (2005-2012). Overall treatment time (OTT) was defined as the time from surgery to the end of radiation therapy. Statistical methods included Cox proportional hazards modeling, which adjusted for clinicopathologic, demographic, and socioeconomic factors. Recursive partitioning analysis (RPA) identified the optimal threshold of OTT via conditional inference trees to estimate the greatest differences in overall survival (OS) on the basis of randomly selected training and validation sets. RESULTS:A total of 16,733 patients were included, with a median follow-up of 37 months. Median OS for OTT in a predefined threshold of ≤ 13 weeks was 10.1 years (95% confidence interval [CI], 9.8 years; not reached) compared with 8.7 years (95% CI, 8.2-9.2 years) in > 13 weeks. On multivariate analysis, OTT of > 13 weeks versus ≤ 13 weeks independently increased mortality risk (hazard ratio, 1.10; 95% CI, 1.04-1.17; P = < 0.001). RPA identified an optimal OTT threshold of 97 days (interquartile range: 96-98 days). The OTT threshold of 97 days was confirmed in a full Cox regression model estimating the risk of death according to overall treatment time as a continuous variable. CONCLUSION/CONCLUSIONS:In this large hospital-based national data, an OTT of greater than approximately 14 weeks most consistently increased the risk of death. LEVEL OF EVIDENCE/METHODS:4. Laryngoscope, 2018.
PMID: 29481712
ISSN: 1531-4995
CID: 2965812
Medications inducing dry mouth and sialorrhea: A guide released by the World Workshop on Oral Medicine VI
ORIGINAL:0012502
ISSN: 0792-9935
CID: 2966182
Hypothesis: The Vestibular and Cerebellar Basis of the Mal de Debarquement Syndrome
The Mal de Debarquement syndrome (MdDS) generally follows sea voyages, but it can occur after turbulent flights or spontaneously. The primary features are objective or perceived continuous rocking, swaying, and/or bobbing at 0.2 Hz after sea voyages or 0.3 Hz after flights. The oscillations can continue for months or years and are immensely disturbing. Associated symptoms appear to be secondary to the incessant sensation of movement. We previously suggested that the illness can be attributed to maladaptation of the velocity storage integrator in the vestibular system, but the actual neural mechanisms driving the MdDS are unknown. Here, based on experiments in subhuman primates, we propose a series of postulates through which the MdDS is generated: (1) The MdDS is produced in the velocity storage integrator by activation of vestibular-only (VO) neurons on either side of the brainstem that are oscillating back and forth at 0.2 or 0.3 Hz. (2) The groups of VO neurons are driven by signals that originate in Purkinje cells in the cerebellar nodulus. (3) Prolonged exposure to roll, either on the sea or in the air, conditions the roll-related neurons in the nodulus. (4) The prolonged exposure causes a shift of the pitch orientation vector from its original position aligned with gravity to a position tilted in roll. (5) Successful treatment involves exposure to a full-field optokinetic stimulus rotating around the spatial vertical countering the direction of the vestibular imbalance. This is done while rolling the head at the frequency of the perceived rocking, swaying, or bobbing. We also note experiments that could be used to verify these postulates, as well as considering potential flaws in the logic. Important unanswered questions: (1) Why does the MdDS predominantly affect women? (2) What aspect of roll causes the prolongation of the tilted orientation vector, and why is it so prolonged in some individuals? (3) What produces the increase in symptoms of some patients when returning home after treatment, and how can this be avoided? We also posit that the same mechanisms underlie the less troublesome and shorter duration Mal de Debarquement.
PMCID:5807657
PMID: 29459843
ISSN: 1664-2295
CID: 2963232
Patterns of care and outcomes of adjuvant therapy for high-risk head and neck cancer after surgery
BACKGROUND:Postoperative chemoradiotherapy (CRT) is considered standard of care in patients with locally advanced head and neck cancer with positive margins and/or extracapsular extension (ECE). METHODS:The National Cancer Data Base (NCDB) was queried to identify patients with squamous cell carcinoma of the head and neck with stages III to IVB disease or with positive margins and/or ECE diagnosed between 2004 and 2012 receiving postoperative radiotherapy (RT). Using univariable and multivariable logistic and Cox regression, we assessed for predictors of CRT use and covariables impacting overall survival (OS), including in a propensity-matched subset. RESULTS:Of 12 224 patients, 67.1% with positive margins and/or ECE received CRT as well as 54.0% without positive margins and/or ECE. The 5-year OS was 61.6% for RT alone versus 67.4% for CRT. In the propensity-matched cohort, OS benefit persisted with CRT, including in a subset with positive margins and/or ECE but not without. CONCLUSION/CONCLUSIONS:Postoperative CRT seems underutilized with positive margins and/or ECE and overutilized without positive margins and/or ECE. The CRT was associated with improved OS but the benefit persisted only in the subset with positive margins and/or ECE.
PMID: 29451961
ISSN: 1097-0347
CID: 2958412
