Studies designed to identify novel methylation events related to cancer often employ cancer cell lines in the discovery phase of the experiments and have a relatively low rate of discovery of cancer-related methylation events. An alternative algorithm for discovery of novel methylation in cancer uses primary tumor-derived xenografts instead of cell lines as the primary source of nucleic acid for evaluation. We evaluated DNA extracted from primary head and neck squamous cell carcinomas (HNSCC), xenografts grown from these primary tumors in nude mice, HNSCC-derived cell lines, normal oral mucosal samples, and minimally transformed oral keratinocyte-derived cell lines using Illumina Infinum Humanmethylation 27 genome-wide methylation microarrays. We found >2,200 statistically significant methylation differences between cancer cell lines and primary tumors and when comparing normal oral mucosa to keratinocyte cell lines. We found no statistically significant promoter methylation differences between primary tumor xenografts and primary tumors. This study demonstrates that tumor-derived xenografts are highly accurate representations of promoter methylation in primary tumors and that cancer derived cell lines have significant drawbacks for discovery of promoter methylation alterations in primary tumors. These findings also support use of primary tumor xenografts for the study of methylation in cancer, drug discovery, and the development of personalized cancer treatments.

BackgroundThere is increasing evidence that biofilms are critical to the pathophysiology of chronic infections including chronic rhinosinusitis (CRS). Until relatively recently, our understanding of biofilms was limited. Recent advances in methods for biofilm identification and molecular biology have offered new insights into the role of biofilms in CRS. With these insights, investigators have begun to investigate novel therapeutic strategies that may disrupt or eradicate biofilms in CRS.ObjectiveThis review seeks to explore the evidence implicating biofilms in CRS, discuss potential anti-biofilm therapeutic strategies, and suggest future directions for research.ResultsThe existing evidence strongly supports the role of biofilms in the pathogenesis of CRS. Several anti-biofilm therapies have been investigated for use in CRS and these are at variable stages of development. Generally, these strategies: 1) neutralize biofilm microbes; 2) disperse existing biofilms; or 3) disrupt quorum sensing. Several of the most promising anti-biofilm therapeutic strategies are reviewed.ConclusionsA better understanding of biofilm function and their contribution to the CRS disease process will be pivotal to the development of novel treatments that may augment and, potentially, redefine the CRS treatment paradigm. There is tremendous potential for future research.

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NA Laryngoscope, 127:E219-E224, 2017.

NA Laryngoscope, 2018.

Objectives/Hypothesis Opioid misuse and diversion is a pressing topic in today's healthcare environment. The objective of this study was to conduct a review of non‐opioid perioperative analgesic regimens following septoplasty, rhinoplasty, and septorhinoplasty. Study Design Evidence‐based systematic review. Methods PubMed, MEDLINE, Cochrane Library, and Embase databases were reviewed for articles related to perioperative analgesic use in septoplasty, rhinoplasty, and septorhinoplasty. Quality of studies were assessed via the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria, Jadad scores, and the Cochrane bias tool. Patient demographic data and clinical outcomes, including medication type, dose, administration time, pain scores, and adverse events, were obtained from included studies. Summary tables detailing the benefits and harms of each investigated regimen are included. Results Thirty‐seven studies met inclusion criteria for this evidence‐based review. The quality of the studies was determined to be of moderate quality based off of GRADE standardized criteria with a mean Jadad score of 3.1. A preponderance of evidence showed reduced perioperative pain scores and rescue analgesic requirements, supporting the use of local anesthetics for analgesic control. Nonsteroidal anti‐inflammatory drugs (NSAIDs) demonstrated similar decreased visual analog scores and postoperative analgesic demand; however, increased adverse events in this class warrant caution. Conclusions Contemporary literature supports the use of NSAIDs, gabapentin, local anesthetics, and α‐agonists as effective perioperative analgesic opioid alternatives for septoplasty and septorhinoplasty. Local anesthetic use is a cost‐effective option resulting in decreased postoperative pain scores and rescue analgesic requirements. Further large‐scale, multi‐institutional, controlled studies are needed to provide definitive recommendations. Level of Evidence NA Laryngoscope, 129:E200–E212, 2019

BACKGROUND Current symptom criteria for identifying patients with chronic rhinosinusitis (CRS) has poor specificity. OBJECTIVE To test the hypothesis that symptoms drawn from the task force on rhinosinusitis (RSTF) criteria and the International Headache Society (IHS) criteria for primary headaches can differentiate CRS patients from those with CRS-symptoms but no evidence for inflammation (non-CRS). METHODS A retrospective cohort study from a total of 140 charts of patients who received a diagnostic CT scan for CRS symptoms in a tertiary care clinic. The study was conducted in two phases: 1) using a retrospective review of otolaryngologist-documented symptoms (ODS) in the medical record and 2) using patient-reported symptoms (PRS) on a prospectively collected customized review of systems form from a separate cohort. A radiographic gold standard differentiated CRS from non-CRS patients. RESULTS Subjects in the CRS and non-CRS group were matched for age and race and almost universally met symptomatic criteria as defined by the RSTF in both study phases. In both study phases, facial pain, but not facial pressure, was negatively predictive for CRS (p<0.05). Similarly, hyposmia was positively predictive, while facial pain of a pulsating quality and photophobia were negatively predictive (p<0.05) although analysis of PRS was significant only when symptom frequency was considered. Nonetheless, significant overlap exists between the prevalence and frequency of symptoms in both groups. CONCLUSION The symptom-based diagnosis of CRS is challenging but symptoms of hyposmia are positively predictive while facial pain, a throbbing quality, headaches and photophobia are negatively predictive and show promise for improving the specificity of CRS diagnosis. Further validation studies are needed.

When the perioperative management of antithrombotic therapy is being decided, 3 critical factors must be considered systematically: the patient's inherent thromboembolic risk, the risk and potential consequences of bleeding related to the procedure, and the timing of interruption of thromboembolic therapy.