Predicting Obstructive Sleep Apnea Status With the Reflux Symptom Index in a Sleep Study Population.

OBJECTIVES/HYPOTHESIS: Otolaryngologic symptoms of obstructive sleep apnea (OSA) and their diagnostic utility are not well studied. We aimed to elucidate the prevalence of otolaryngologic symptoms among patients being evaluated for OSA. Given findings that the Reflux Symptom Index (RSI) was strongly associated with OSA status, we evaluated the diagnostic utility of the RSI for predicting OSA status. STUDY DESIGN: Cross-sectional. METHODS: We recruited 101 adults presenting for ambulatory polysomnograms to the Northwestern Sleep Disorders Center from July 2017 to July 2018. The Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Leicester Cough Questionnaire (LCQ), RSI, Gastroesophageal Reflux Disease Questionnaire, Sino-Nasal Outcome Test-22, Nasal Obstruction Symptom Evaluation, Eustachian Tube Dysfunction Questionnaire 7, and Headache Impact Test were administered. Polysomnogram results were subsequently obtained. Patients with OSA (apnea-hypopnea index ≥ 5) and without OSA were compared. RESULTS: Of the 101 participants, 98 had valid sleep study results. Of those, 72 were diagnosed with OSA and 26 were not. The two groups differed significantly in age and body mass index (BMI). Of the questionnaires, only the RSI and LCQ means differed significantly, with worse symptoms in the OSA group (P = .003 and .014, respectively). Upon univariate regression, age, BMI, and RSI were associated with OSA status. Using regression coefficients, a clinical score of 2 (RSI) + 1.5 (BMI) + age yielded a diagnostic model (C-statistic = 0.807, P < .001). A threshold score of 104.21 was 76.4% sensitive and 73.1% specific. CONCLUSIONS: Patients with OSA have worse symptoms of laryngopharyngeal reflux as measured by the RSI. The addition of the RSI to the recognized factors of age and BMI improves diagnostic utility for OSA. LEVEL OF EVIDENCE: 2 Laryngoscope, 2020.

Female Representation in Otolaryngology Leadership Roles.

OBJECTIVES/HYPOTHESIS: Characterization of leadership within otolaryngology is key to evaluating trends and promoting program advancement. This study evaluates representation of women in otolaryngology holding residency and fellowship directorships, or chair positions, comparing sex differences in academic rank, years in practice, and scholarly activity. STUDY DESIGN: Cross sectional analysis. METHODS: A comprehensive list of otolaryngology residency and fellowship directors from Accreditation Council for Graduate Medical Education-accredited programs in 2017 to 2018 was compiled. Academic rank and years in practice were determined from departmental websites, with online search tools used as secondary resources. The h-index was utilized as a measure of research productivity. Regression analysis was performed to analyze these variables. RESULTS: Among the 306 directorships, women held 57 (18.6%) of these positions, 27 (26.5%) residency and 30 (14.7%) fellowship directorships. Of the 99 chair positions, five (5.1%) were held by women. The majority (53.6%) of male directors were full professors, whereas only 26.3% of females were full professors (P = .04). Mean years in practice for female directors (13.9 ± 6.8) was less than that of male directors (20.3 ± 9.4, P < .0001). Similarly, mean h-index for female directors (11 ± 7.2) was lower than for males (17.5 ± 12.5, P = .0001). After controlling for academic rank and years of practice in a multivariable regression, the h-index remained lower for women than for men (P = .03). CONCLUSIONS: Women are disproportionately underrepresented in positions of residency and fellowship directorships, and chair positions, consistent with other specialties. Women in leadership had lower academic ranks, fewer years of practice, and lower h-indices than their male counterparts. This may represent a shift in academic otolaryngology as female otolaryngologists seek early involvement in leadership. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1664-1669, 2020.

Changing practice: Trends in skeletal surgery for obstructive sleep apnea.

OBJECTIVES/HYPOTHESIS: The objective of this study was to systematically review the English literature for articles that have described skeletal surgeries in the treatment of obstructive sleep apnea in both adults and children. From these articles trends and patterns in the treatment of OSA with skeletal procedures are described. STUDY DESIGN: Three databases including MEDLINE, Google Scholar and the Cochrane Library were searched through May 1, 2018. METHODS: The systematic and independent literature reviews were performed and the determination of included studies was made by consensus. Relevant studies were examined based on six categories of skeletal surgery: 1) Hyoid Advancement 2) Genioplasty/Genioglossus Advancement 3) Maxillary Expansion 4) Maxillomandibular Advancement 5) Mandibular Distraction and 6) Maxillomandibular Expansion. RESULTS: 1875 studies were analyzed for inclusion of which 414 were ultimately included in our analysis. A steady increase in the publication of articles pertaining to maxillary expansion and maxillomandibular advancement was identified. Research interest in hyoid advancement and genioplasty/genioglossus advancement has declined in the past decade. CONCLUSIONS: Changing trends in skeletal surgery for OSA offer exciting and efficacious therapeutic surgical modalities. MMA is the most widely studied and efficacious multi-level surgery for OSA today. Newer modalities such as adult maxillary expansion offer encouraging early results with minimal complication rates, and further study should be directed in this area.

Long-term Results for Maxillomandibular Advancement to Treat Obstructive Sleep Apnea: A Meta-analysis.

OBJECTIVE: To examine outcomes in the intermediate term (1 to <4 years), long term (4 to <8 years), and very long term (≥8 years) for maxillomandibular advancement (MMA) as treatment for obstructive sleep apnea (OSA). DATA SOURCES: The Cochrane Library, Google Scholar, Embase, Cumulative Index to Nursing and Allied Health, and PubMed/MEDLINE. REVIEW METHODS: Three authors systematically reviewed the international literature through July 26, 2018. RESULTS: A total of 445 studies were screened, and 6 met criteria (120 patients). Thirty-one patients showed a reduction in apnea-hypopnea index (AHI) from a mean 48.3 events/h (95% CI, 42.1-54.5) pre-MMA to 8.4 (95% CI 5.6, 11.2) in the intermediate term. Fifty-four patients showed a reduction in AHI from a mean 65.8 events/h (95% CI, 58.8-72.8) pre-MMA to 7.7 (95% CI 5.9, 9.5) in the long term. Thirty-five showed a reduction in AHI from a mean 53.2 events/h (95% CI 45, 61.4) pre-MMA to 23.1 (95% CI 16.3, 29.9) in the very long term. Improvement in sleepiness was maintained at all follow-up periods. Lowest oxygen saturation improvement was maintained in the long term. CONCLUSION: The current international literature shows that patients with OSA who were treated with MMA maintained improvements in AHI, sleepiness, and lowest oxygen saturation in the long term; however, the mean AHI increased to moderate OSA in the very long term. Definitive generalizations cannot be made, and additional research providing individual patient data for the intermediate term, long term, and very long term is needed.

Are chronic cough and laryngopharyngeal reflux more common in obstructive sleep apnea patients?

OBJECTIVES/HYPOTHESIS: To assess if there is a significant difference in the prevalence and severity of chronic cough symptoms in obstructive sleep apnea (OSA) patients versus non-OSA patients and examine this relationship in regard to laryngopharyngeal reflux (LPR) symptoms. STUDY DESIGN: Prospective cohort study. METHODS: Patients referred to Northwestern Medicine Sleep Lab for home sleep testing were enrolled. Patients filled out the Leicester Cough Questionnaire (LCQ) and Reflux Symptom Index (RSI) before completing sleep testing. Home sleep testing results were reviewed, and patients were separated into non-OSA and OSA groups by standard Apnea-Hypopnea Index (AHI) criteria. Demographic characteristics and questionnaire scores of the two groups were compared. The relationship between OSA severity, as determined by AHI, and LCQ and RSI scores was assessed. RESULTS: Of the 52 patients enrolled, 33 patients met criteria for OSA and 19 patients did not. Comparing patients without OSA versus those with OSA, there was a significant difference in mean LCQ score (129.9 vs. 120.0, respectively; P = .02), implying worse cough symptoms among OSA patients, and mean RSI score (3.2 vs. 11.2, respectively; P = .0013), implying worse upper-airway reflux symptoms among OSA patients. There was a significant correlation between LCQ score and AHI (r = -0.39, P = .0061) and between RSI score and AHI (r = 0.37, P = .0078). CONCLUSIONS: OSA patients demonstrate worse chronic cough and LPR-related quality of life versus non-OSA patients. Furthermore, the severity of these quality-of-life measures was correlated with the severity of the AHI. Chronic cough and particularly the pharyngeal LPR symptoms may be associated with the presence and severity of OSA. LEVEL OF EVIDENCE: 2 . Laryngoscope, 129:1244-1249, 2019.

Clinical Trials in Obstructive Sleep Apnea: Recognizing Trends and Future Opportunities.

OBJECTIVES/HYPOTHESIS: Examine US and international clinical trials in obstructive sleep apnea (OSA) to characterize researchers involved, interventions being studied, and opportunities for future investigation. STUDY DESIGN: Retrospective database review. METHODS: The information from ClinicalTrials.gov was used to assess OSA clinical trials between 1999 and 2017. Information was gathered on principle investigator (PI) demographics, interventions studied, study funding source, and regional distribution of research institutions. RESULTS: There were 813 clinical trials studied. The majority of trials examined continuous positive airway pressure interventions (43.7%), with pharmacotherapies being the second most commonly investigated treatment (19.2%). Surgical interventions made up 10.7% (n = 87) of clinical trials for OSA. Most studies were based internationally (59.9%). PIs were predominantly male (72.0%); 72.7% had an MD and 28.6% had a PhD. There were no significant differences in funding source (National Institutes of Health vs. industry, P = .14) or institutional geography (international vs. US, P = .73) between surgical and nonsurgical studies. Surgical trials were significantly more likely to have a male PI and involve pediatric patients compared to nonsurgical trials (P < .001). Otolaryngologists represented 9.2% of all PIs and had similar rates of NIH funding compared to other medical specialists (P = .22). CONCLUSIONS: This study provides a broad overview of past, current, and future treatment paradigms for OSA. Sleep surgery, specifically otolaryngology, is a small voice in the overall landscape of clinical trials for OSA. This information can help guide future research efforts and direct our specialty when setting priorities regarding research funding while encouraging a broad and interdisciplinary pursuit. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1940-1944, 2019.

Mandibular advancement for pediatric obstructive sleep apnea: A systematic review and meta-analysis.

OBJECTIVES: Mandibular distraction osteogenesis and mandibular advancement, collectively referred to as mandibular advancement surgeries (MAS), have been used to treat children with mandibular insufficiency and obstructive sleep apnea (OSA). The objective is to perform a systematic review and meta-analysis for MAS as treatment for obstructive sleep apnea. METHODS: Three authors searched multiple databases (including PubMed/Medline) from inception through April 25, 2018. RESULTS: 1198 studies were screened, 128 were downloaded and 37 met inclusion criteria (376 patients, mean age: 1.5 years). Meta-analysis demonstrated a reduction in the apnea-hypopnea index (AHI), from a mean ± SD of 41.1 ± 35.8 to 4.5 ± 6.0 events per hour (89.1% decrease). The lowest oxygen saturation (LSAT) in 211 patients increased from a mean ± SD of 76.8 ± 13.0 to 91.1 ± 8.6 (14.3 oxygen saturation point increase). Individual patient data (105 patients) demonstrated AHI surgical success in 73.4% of patients and respiratory disturbance index (RDI) surgical success in 100% of patients. AHI surgical cure was seen in 25.5% of patients and RDI surgical cure was seen in 37.5% of patients. CONCLUSIONS: This study's major finding is that obstructive sleep apnea has dramatically improved in pediatric patients with mandibular insufficiency when they have been treated with mandibular advancement or mandibular distraction osteogenesis.

YouTube as a source of information for obstructive sleep apnea.

PURPOSE: Assess the quality of information on obstructive sleep apnea (OSA) presented on YouTube for patients. MATERIALS AND METHODS: "Obstructive sleep apnea" was entered into the YouTube search. Two independent reviewers categorized and analyzed videos utilizing a customized scoring-system along with search position, likes, and views. RESULTS: Forty-eight videos were analyzed. Most were educational (52.1%). Educational and news videos had significantly higher scores, but had no significant differences in search position, likes/day, or views/day. Most videos mentioned positive airway pressure (65%), and nearly half (44%) mentioned mandibular devices in the management of OSA. Few videos discussed surgery (13%) or otolaryngology (15%). CONCLUSION: YouTube is a promising source of information for OSA patients. Educational and news videos are of highest quality. General quality measures like search position, views, and likes are not correlated with formally scored value. Sleep surgery and otolaryngologists are minimally mentioned, representing an opportunity for improvement.

Neuromuscular function of the soft palate and uvula in snoring and obstructive sleep apnea: A systematic review.

OBJECTIVE: A collapsible upper airway is a common cause of obstructive sleep apnea. The exact pathophysiology leading to a more collapsible airway is not well understood. A progressive neuropathy of the soft palate and pharyngeal dilators may be associated with the progression of snoring to OSA. The purpose of this study is to systematically review the international literature investigating the neurophysiologic changes in the soft palate and uvula that contribute to progression from snoring to OSA. METHODS: PubMed/MEDLINE and 4 other databases were systematically searched through July 4, 2017. Eligibility: (1) Patients: controls, snoring or OSA patients (2) Intervention: neuromuscular evaluation of the palate and/or uvula (3) Comparison: differences between controls, snoring and OSA patients (4) Outcomes: neuromuscular outcomes (5) Study design: Peer reviewed publications of any design. RESULTS: 845 studies were screened, 76 were downloaded in full text form and thirty-one studies met criteria. Histological studies of the soft palate demonstrated diffuse inflammatory changes, muscular changes consistent with neuropathy, and neural aberrancies. Sensory testing studies provided heterogeneous outcomes though the majority favored neuronal dysfunction. Studies have consistently demonstrated that increasing severity of snoring and sleep apnea is associated with worsening sensory nerve function of the palate in association with atrophic histological changes to the nerves and muscle fibers of the soft palate and uvula. CONCLUSIONS: Recent evidence highlighted in this systematic review implicates the role of neurogenic pathology underlying the loss of soft palate and/or uvular tone in the progression of snoring to sleep apnea.

Opioid Stewardship in Otolaryngology: State of the Art Review.

Objective The United States is facing an epidemic of opioid addiction. Deaths from opioid overdose have quadrupled in the past 15 years and now surpass annual deaths during the height of the human immunodeficiency virus epidemic. There is a link between opioid prescriptions after surgery, opioid misuse, opioid diversion, and use of other drugs of abuse. As surgeons, otolaryngologists contribute to this crisis. Our objective is to outline the risk of abuse from opioids in the management of acute postoperative pain in otolaryngology-head and neck surgery (OHNS) and strategies to avoid misuse. Data Sources PubMed/MEDLINE. Review Methods We conducted a review of the literature on the rate of opioid abuse after surgery, methods of safe opioid use, and strategies to minimize the dangers of opioids. Conclusions Otolaryngologists have a responsibility to treat pain. This begins preoperatively by discussing perioperative pain control and developing a personalized pain control plan. Patients should be aware that opioids carry significant risks of adverse events and abuse. Perioperative use of multimodal nonopioid agents enables pain control and avoidance of opioids in many otolaryngologic cases. When this approach is inadequate, opioids should be used in short duration under close surveillance. Institutional standards for opioid prescribing after common procedures can minimize misuse. Implications for Practice Otolaryngologists need to acknowledge the potential harm that opioids cause. It is essential that we evaluate our practices to ensure that opioids are used responsibly. Furthermore, opioid stewardship should become a priority in otolaryngology.

The Association of External Transfer Status with Adverse Outcomes in Otolaryngology.

Objective To compare rates of morbidity and mortality in patients treated by otolaryngologists who undergo interhospital transfers vs those who do not and to quantify conditions requiring interhospital transfers in this population. Study Design Cohort study. Setting American College of Surgeons National Surgical Quality Improvement Program. Subjects and Methods We identified patients requiring surgery by otolaryngologists in the National Surgical Quality Improvement Program database from 2006 to 2013. We compared patients who were transferred from an outside institution to those admitted from home. Multivariate regression was used to adjust for patient characteristics, comorbidities, and case mix. The primary outcome was overall morbidity and mortality within 30 days of surgery. Results We identified 60,498 patients; 488 (0.8%) were transferred from another institution. Operations that were more common in the transferred group were incision and drainage (24.0% vs 1.2%), facial trauma repair (9.0% vs 3.1%), and oropharyngeal hemorrhage control (3.9% vs 0.4%). External transfer patients had significantly longer hospital stays (44.1% vs 4.4% >7 days, P < .05). On unadjusted analysis, transferred patients had a significantly higher rate of morbidity and mortality (odds ratio [OR], 11.3; 95% confidence interval [CI], 9.4-13.5). On multivariate analysis, transferred patients had a significantly greater rate of morbidity and mortality (OR, 3.1; 95% CI, 2.4-4.0). Conclusion Transfer from another institution is associated with worse outcomes independent of case mix, demographics, and preoperative comorbidities in acute otolaryngology conditions requiring surgery. Practitioners should be aware of this when caring for transfer patients, and transfer status should be considered when measuring hospital quality.

Publication trends and levels of evidence in obstructive sleep apnea literature.

OBJECTIVES/HYPOTHESIS: Examine trends in clinical research and levels of evidence related to obstructive sleep apnea (OSA) in the medical literature. Describe the features and trends of OSA research within otolaryngology journals. STUDY DESIGN: Retrospective analysis. METHODS: Review of OSA research articles from 2006, 2011, and 2016 in four leading medical sleep and otolaryngology journals. Level of evidence was graded, and study characteristics were measured. RESULTS: Seven hundred eight total articles were reviewed. OSA articles significantly increased in both number and proportion of total articles in the medical sleep (P < .001) and otolaryngology (P = .004) journals. Surgically focused articles did not significantly increase in either literature. There was no significant difference between medical sleep and otolaryngology literature levels of evidence regarding OSA, and no trend toward higher levels of evidence over time. Medical sleep publications had significantly higher proportions of grant-funded (P < .001) and National Institutes of Health (NIH)-funded (P < .001) publications versus otolaryngology journals. Over time, otolaryngology journals had decreasing numbers of grant-funded and NIH-funded projects. CONCLUSIONS: OSA research is increasingly present in medical sleep and otolaryngology literature. Levels of evidence are modest for the two specialties, and have shown no trend toward increasing over time. Concurrently, otolaryngologists are less likely to be grant funded than their medical colleagues, and sleep surgery has stagnated in the studied journals. This study encourages continued efforts to publish high-quality research on OSA. It may also help guide our specialty when setting priorities regarding research funding and support for sleep surgeons. LEVEL OF EVIDENCE: NA Laryngoscope, 128:2193-2199, 2018.

Mandibular advancement for adult obstructive sleep apnea: A systematic review and meta-analysis.

OBJECTIVES: Patients with mandibular insufficiency can be predisposed to obstructive sleep apnea (OSA). The objective of this study was to systematically review the international literature for mandibular advancement surgeries (MAS) as treatment for adult OSA, and then to perform a meta-analysis. METHODS: Four authors searched five databases from the inception of each database through April 5, 2017. The PRISMA statement was followed. RESULTS: 972 studies were screened, 84 were downloaded, and 11 (57 patients) met criteria. In patients with mandibular insufficiency, MAS reduced apnea-hypopnea index (AHI) (50 patients) from 45.9 ± 24.7 to 6.2 ± 10.4 events/h (87% decrease). The lowest oxygen saturation (LSAT) (55 patients) increased from 71.9 ± 14.6% to 89.0 ± 11.0%. The AHI mean difference was -34.8 events/h [95% CI -43.9, -25.8]. The AHI standardized mean difference was -1.8 [95% CI -2.5, -1.2] (indicating a large magnitude of effect). Surgical cure was seen in 75% of those with >16 mm of mandibular advancement vs. 35% of those with <16 mm of advancement [Odds Ratio 5.5; 95% CI 1.06-28.4; Chi Square p = 0.035]. CONCLUSIONS: The current literature supports isolated mandibular advancement as an efficacious treatment modality for adult OSA in select patients with mandibular insufficiency.

The state of academic sleep surgery: A survey of United States residency and fellowship programs.

OBJECTIVES/HYPOTHESIS: Our objectives were to describe otolaryngology residency programs' experience in and attitudes toward sleep surgery, and describe current otolaryngology sleep fellowships and their impact on future academic practice. STUDY DESIGN: E-mail survey. METHODS: A survey was e-mailed to program directors of 106 Accreditation Council for Graduate Medical Education-accredited otolaryngology residencies assessing resident sleep medicine experience, program satisfaction, and impact of sleep faculty. A separate survey was sent to directors of the seven sleep medicine otolaryngology fellowships. Frequency of graduates pursuing academic careers was examined. RESULTS: Forty-six (43.4%) residency programs responded. Thirty-one (67.4%) have a faculty member with any time spent practicing sleep medicine or surgery. Nineteen (41.3%) have a faculty member with >50% dedicated sleep practice and/or who is board certified in sleep medicine. These programs were significantly more likely to respond "extremely" or "very" satisfied with resident sleep exposure than those without (P < .001). Most programs (69.6%) "strongly agreed" or "agreed" their program would benefit from a dedicated sleep surgeon; there was no significant difference in response rates between programs already with and those without dedicated sleep faculty. All fellowship directors responded. In the past 5 years these programs have trained 11 total fellows. Ten (90.9%) have remained in academic practice. CONCLUSIONS: There is significantly increased satisfaction in resident sleep education at otolaryngology programs with dedicated sleep providers. Concurrently, there is strong program interest in sleep surgeons' involvement in resident training. Sleep fellowships are producing surgeons who pursue academic careers. This study provides support to training fellowship-specialized sleep surgeons and encouraging otolaryngology sleep faculty. LEVEL OF EVIDENCE: NA Laryngoscope, 127:2423-2428, 2017.

Sleep Surgery in the Elderly: Lessons from the National Surgical Quality Improvement Program.

Objective Assess the frequency and nature of postoperative complications following sleep surgery. Examine these issues specifically in elderly patients to provide guidance for their perioperative care. Study Design Retrospective cohort study. Setting American College of Surgeons National Surgical Quality Improvement Program. Methods We identified patients with obstructive sleep apnea undergoing sleep surgery procedures from 2006 to 2013 in the American College of Surgeons National Surgical Quality Improvement Program, a multi-institutional outcomes program designed to improve surgical quality. We analyzed patients by comparing age groups: <65 and ≥65 years. Summary data were analyzed, and multivariate regression was used to adjust for patient characteristics, comorbidities, and surgical procedure. Results We identified 2230 patients who had sleep surgery, which included 2123 patients <65 years old and 107 patients ≥65 years old. Elderly patients were significantly more likely to have hypertension requiring medication ( P < .001) and higher American Society of Anesthesiologists scores ( P < .001). There were no significant differences in the rates of nasal ( P = .87), palate ( P = .59), tongue base ( P = .73), and multilevel ( P = .95) surgery being performed on both groups of patients. Elderly patients had higher rates of wound complications and urinary tract infections as compared with younger patients. On multivariate analysis, age ≥65 was significantly associated with complications from sleep surgery (odds ratio, 2.35; 95% CI, 1.04-5.35). Conclusion Elderly patients undergoing sleep surgery have increased postoperative complication risk as compared with younger patients treated similarly. This information can help direct quality improvement efforts in the care of older patients.

Management of hearing loss and the normal ear in cases of unilateral Microtia with aural atresia.

OBJECTIVES/HYPOTHESIS: To identify the rate of hearing loss related to middle ear disease and the frequency of tympanostomy tube (TT) insertion in the contralateral ear of patients with unilateral microtia/aural atresia. STUDY DESIGN: Retrospective case series of patients less than 3 years of age with unilateral microtia/aural atresia treated at an urban, tertiary care children's hospital from 2008 to 2013. METHODS: Clinical and audiologic data were reviewed. Statistical analysis was performed to determine the relative risk of TT insertion in the normal ear. RESULTS: A total of 72 patients were included for analysis. The average age of patients at their initial otolaryngology visit was 3.3 months (range 0.08-1.67 years); 38 (52.8%) patients were males. Aural atresia involved the right ear in 43 (59.7%) cases. Five (6.9%) patients were syndromic. Abnormal audiometric testing of the normal ear was noted in 12 (16.7%), and 14 (19.4%) underwent TT during the first 3 years of life. Twelve children (85.7%) who had a TT placed were nonsyndromic. When compared to published norms for TT placement in the general population (6.8% of children < 3 year of age), a greater proportion of children with unilateral microtia/aural atresia had TT placement in the normal ear (z = 4.26, P < 0.0001). CONCLUSION: Patients with unilateral microtia/aural atresia have increased rates of hearing loss and middle ear effusion leading to TT in their normal ear at a higher rate versus the general population. This information can help guide more vigilant care and audiologic follow-up in affected children. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1470-1474, 2016.

National Institutes of Health Funding for Obstructive Sleep Apnea: An Opportunity for Otolaryngologists.

OBJECTIVE: To describe current levels and trends of funding for the National Institutes of Health (NIH) in obstructive sleep apnea (OSA) and to recognize the current status of otolaryngologists in OSA research. STUDY DESIGN: Scientometric analysis. METHODS: The NIH RePORTER database was queried for the search term "obstructive sleep apnea" for all available years. Sex, degree, academic department, NIH funding source, geography, funding totals and years, and h-index of principal investigators (PIs) were collected and summarized. RESULTS: A total of 397 projects spanning 1242 total funding years were funded. Of the 273 individual PIs, 33.3% (91/273) were female. Regarding credentials, 52.4% of PIs (143/273) were MD or MD/PhD, and 41.0% (112/273) were PhD alone. Academic departments of PIs were most often medicine (34.1%), pediatrics (12.1%), cell biology/physiology (10.6%), and psychiatry (7.7%). Seven otolaryngology faculty members had received NIH funding for OSA research (2.6% of total PIs) since 2000. They accounted for 8 grants (0.25% of total grants) and $7,235,729 (1.5% of total dollars) of research funding. CONCLUSION: Despite studies showing increasing levels of OSA surgery being performed and major areas of research and clinical opportunity, otolaryngologists represent a small minority of OSA research funding. This information may help direct our specialty when setting priorities regarding research funding, as research into the basic science and clinical management of OSA represents a broad and interdisciplinary pursuit.

Lack of association of BRAF mutation with negative prognostic indicators in papillary thyroid carcinoma: the University of California, San Francisco, experience.

IMPORTANCE: Papillary thyroid carcinoma (PTC) is the most common endocrine neoplasm. B-type raf kinase (BRAF) V600E mutation has been proposed as a negative prognostic indicator in PTC, and patients harboring it should receive more aggressive initial therapy. OBJECTIVE: To assess the significance of BRAF V600E mutation in PTC in the largest US sample to date. DESIGN: We identified patients from our institution's pathology archives diagnosed as having PTC and meeting criteria for BRAF mutation testing. Medical records were analyzed for BRAF status (positive or negative) and a list of standardized clinicopathologic features. PARTICIPANTS: A total of 429 patients with PTC at an academic medical center. MAIN OUTCOMES AND MEASURES: Clinicopathologic features in patients with PTC with and without BRAF mutation. RESULTS: Of 429 cases with PTC, 314 (73.2%) were positive for the BRAF mutation and 115 (26.8%) tested negative. BRAF mutation was significantly associated with tumor margin positivity (P = .03) and lymph node metastasis (P = .002) on univariate analysis but not on multivariate study. BRAF mutation was a predictor of male sex (odds ratio [OR], 3.2; 95% CI, 1.4-7.2), total thyroidectomy (OR, 2.6; 95% CI, 1.1-6.2), and a negative predictor of follicular variant PTC (OR, 0.1; 95% CI, 0.1-0.4). There was no significant association between BRAF positivity and tumor multicentricity, lymphovascular invasion, extranodal extension, central neck involvement, advanced stage (stage III or IV), and distant metastasis. CONCLUSIONS AND RELEVANCE: BRAF V600E mutation has been extensively studied in relation to negative prognostic indicators in PTC, with no consistent relationship emerging. Two recent meta-analyses showed an overall association between BRAF status and aggressive disease features and called for tailoring treatment plans in patients accordingly. In this, the largest US study to date, BRAF status was not significantly associated with most clinicopathologic features suggestive of more aggressive disease.

Wild-type EGFR is stabilized by direct interaction with HSP90 in cancer cells and tumors.

The epidermal growth factor receptor (EGFR) has been targeted for inhibition using tyrosine kinase inhibitors and monoclonal antibodies, with improvement in outcome in subsets of patients with head and neck, lung, and colorectal carcinomas. We have previously found that EGFR stability plays a key role in cell survival after chemotherapy and radiotherapy. Heat shock protein 90 (HSP90) is known to stabilize mutant EGFR and ErbB2, but its role in cancers with wild-type (WT) WT-EGFR is unclear. In this report, we demonstrate that fully mature, membrane-bound WT-EGFR interacts with HSP90 independent of ErbB2. Further, the HSP90 inhibitors geldanamycin (GA) and AT13387 cause a decrease in WT-EGFR in cultured head and neck cancer cells. This decrease results from a significantly reduced half-life of WT-EGFR. WT-EGFR was also lost in head and neck xenograft specimens after treatment with AT13387 under conditions that inhibited tumor growth and prolonged survival of the mice. Our findings demonstrate that WT-EGFR is a client protein of HSP90 and that their interaction is critical for maintaining both the stability of the receptor as well as the growth of EGFR-dependent cancers. Furthermore, these findings support the search for specific agents that disrupt HSP90's ability to act as an EGFR chaperone.