Choice of vector and surgical approach enables efficient cochlear gene transfer in nonhuman primate.

Inner ear gene therapy using adeno-associated viral vectors (AAV) promises to alleviate hearing and balance disorders. We previously established the benefits of Anc80L65 in targeting inner and outer hair cells in newborn mice. To accelerate translation to humans, we now report the feasibility and efficiency of the surgical approach and vector delivery in a nonhuman primate model. Five rhesus macaques were injected with AAV1 or Anc80L65 expressing eGFP using a transmastoid posterior tympanotomy approach to access the round window membrane after making a small fenestra in the oval window. The procedure was well tolerated. All but one animal showed cochlear eGFP expression 7-14 days following injection. Anc80L65 in 2 animals transduced up to 90% of apical inner hair cells; AAV1 was markedly less efficient at equal dose. Transduction for both vectors declined from apex to base. These data motivate future translational studies to evaluate gene therapy for human hearing disorders.

Associations of self-reported obstructive sleep apnea with total and site-specific cancer risk in older women: a prospective study.

BACKGROUND AND OBJECTIVES: Chronic intermittent hypoxia resulting from obstructive sleep apnea (OSA) may activate multiple carcinogenic pathways and lead to cancer development. METHODS: We prospectively examined the association between OSA and cancer risk among 65,330 women in the Nurses' Health Study who were free of cancer in 2008 (mean age: 73.3 years). Incident cancer diagnoses were collected until 2016 and confirmed by pathology reports. Clinically diagnosed OSA was self-reported in 2008 and updated in 2012. We used time-dependent Cox regression to estimate hazard ratios (HR) for the associations of OSA with total and site-specific cancer risk. RESULTS: We documented 5,257 incident cancer diagnoses during follow-up. In the age-adjusted model, OSA was associated with a 15% (95% CI: 1.03, 1.29) increase in total cancer risk. The association became nonsignificant after adjustment for multiple cancer risk factors (HR: 1.08; 95% CI: 0.96, 1.21). When examining cancer risk by site, OSA was associated with significantly increased risk for lung (fully adjusted HR: 1.52; 95% CI: 1.07, 2.17), bladder (fully adjusted HR: 1.94; 95% CI: 1.12, 3.35), and thyroid cancer (fully adjusted HR: 2.06; 95% CI: 1.01, 4.22) and possibly increased risk for kidney cancer (fully adjusted HR: 1.59; 95% CI: 0.84, 3.01). When grouping cancer sites by risk factor profiles, OSA was positively associated with smoking-related cancers (fully adjusted HR: 1.37; 95% CI: 1.11, 1.67), and this association was stronger in never smokers than ever smokers. CONCLUSION: While OSA was not independently associated with overall cancer risk in older women, significant associations were observed for smoking-related cancers, especially in nonsmokers.

Cigarette Smoking, Smoking Cessation, and Risk of Hearing Loss in Women.

BACKGROUND: Previous studies demonstrated higher risk of hearing loss among cigarette smokers, but longitudinal data on whether the risk is influenced by smoking cessation are limited. We prospectively investigated relations between smoking, smoking cessation, and risk of self-reported moderate or worse hearing loss among 81,505 women in the Nurses' Health Study II (1991-2013). METHODS: Information on smoking and hearing status was obtained from validated biennial questionnaires. Cox proportional hazards regression was used to estimate multivariable-adjusted relative risks (MVRR, 95% confidence interval). RESULTS: During 1,533,214 person-years of follow-up, 2760 cases of hearing loss were reported. Smoking was associated with higher risk of hearing loss and the risk tended to be higher with greater number of pack-years smoked. Compared with never smokers, the MVRR (95% confidence interval) among past smokers with 20+ pack-years of smoking was 1.30 (1.09-1.55) and 1.21 (1.02-1.43) for current smokers. The magnitude of elevated risk diminished with greater time since smoking cessation. Compared with never smokers, the MVRR among smokers who quit <5 years prior was 1.43 (1.17-1.75); 5-9 years prior was 1.27 (1.03-1.56); 10-14 years prior was 1.17 (0.96-1.41); and plateaued thereafter. Additional adjustment for pack-years smoking attenuated the results. CONCLUSIONS: The higher risk of hearing loss associated with smoking may diminish over time after quitting.

United States-based global otolaryngology surgery: A call to more horizontal sustainable efforts.

OBJECTIVE: To examine global surgery involvement among general members of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and characterize international otolaryngology surgical interventions. METHODS: Data on global surgery involvement were derived from responses provided by voluntary online survey respondent members of the AAO-HNS, obtained in October 2017. These data were compared against World Bank metrics of national health expenditure and surgical specialists per capita as benchmarks for need. RESULTS: There were 362 responses (response rate of 3.7%). A large proportion of respondents reported being involved in global surgery (61.3%). Locations where respondents worked included: South America (13.3%), Central America (17.7%), Caribbean (10.2%), Europe (4.1%), Africa (16.3%), Asia (16.6%), the Middle East (4.1%), and Oceania (3.6%). A greater proportion of respondents reported traveling to locations that have lower health care expenditure per capita and lower mean number of surgical specialists per 100,000 people, according to data from the World Bank. The primary purpose of trips was most commonly surgical mission (60.3%), followed by education (37.8%), and research (1.9%). CONCLUSION: Members of the AAO-HNS are active in global surgery efforts around the world. Collaboration among members of the AAO-HNS may serve to improve long-term sustainability of these efforts.

A Population-Based Study of the Bidirectional Association Between Obstructive Sleep Apnea and Type 2 Diabetes in Three Prospective U.S. Cohorts.

OBJECTIVE: Multiple lines of evidence support a complex relationship between obstructive sleep apnea (OSA) and diabetes. However, no population-based study has evaluated the potential bidirectional association between these two highly prevalent disorders. RESEARCH DESIGN AND METHODS: We followed 146,519 participants from the Nurses' Health Study (NHS; 2002-2012), Nurses' Health Study II (NHSII; 1995-2013), and Health Professionals Follow-up Study (HPFS; 1996-2012) who were free of diabetes, cardiovascular disease, and cancer at baseline. Cox proportional hazards models were used to estimate hazard ratios (HRs) for developing diabetes according to OSA status. In parallel, we used similar approaches to estimate risk of developing OSA according to diabetes status among 151,194 participants free of OSA, cardiovascular disease, and cancer at baseline. In all three cohorts, diagnoses of diabetes and OSA were identified by validated self-reports. RESULTS: Similar results were observed across the three cohorts. In the pooled analysis, 9,029 incident diabetes cases were identified during follow-up. After accounting for potential confounders, the HR (95% CI) for diabetes was 2.06 (1.86, 2.28) comparing those with versus without OSA. The association was attenuated but remained statistically significant after further adjusting for waist circumference and BMI (HR 1.37 [95% CI 1.24, 1.53]), with the highest diabetes risk observed for OSA concomitant with sleepiness (1.78 [1.13, 2.82]). In the second analysis, we documented 9,364 incident OSA cases during follow-up. Compared with those without diabetes, the multivariable HR (95% CI) for OSA was 1.53 (1.32, 1.77) in individuals with diabetes. Adjustment for BMI and waist circumference attenuated the association (1.08 [1.00, 1.16]); however, an increased risk was observed among those with diabetes who used insulin compared with those without diabetes (1.43 [1.11, 1.83]), particularly among women (1.60 [1.34, 1.89]). CONCLUSIONS: OSA is independently associated with an increased risk of diabetes, whereas insulin-treated diabetes is independently associated with a higher risk of OSA, particularly in women. Clinical awareness of this bidirectional association may improve prevention and treatment of both diseases. Future research aimed at elucidating the mechanisms that underlie each association may identify novel intervention targets.

Resident responses to after-hours otolaryngology patient phone calls: An overlooked aspect of residency training?

OBJECTIVES/HYPOTHESIS: Otolaryngology residents are often responsible for triaging after-hours patient calls. However, residents receive little training on this topic. Data are limited on the clinical content, reporting, and management of otolaryngology patient calls. This study aimed to characterize the patient concerns residents handle by phone and their subsequent management and reporting. STUDY DESIGN: Retrospective review. METHODS: Five hundred consecutive after-hours patient calls in a tertiary pediatric hospital were reviewed. Data collected included patient and caller demographics, clinical concerns, surgical history, recommendations, and subsequent emergency department (ED) visits. RESULTS: On average, 3.7 calls occurred per shift, 2.8 on weekday and 5.9 on weekend shifts. Mean patient age was 6.6 years. Mothers (71%) called most frequently. The majority of calls were postoperative (64.2%). Of postoperative calls, most occurred within 3 days of surgery (52.3%). Most calls were for surgical site bleeding (19.9%). Residents recommended ED evaluation for 17.2% of calls, of which 20.9% returned to the primary institution ED. ED evaluation was recommended more frequently for postoperative patients (P = .040), particularly following adenotonsillectomy (51.2%) or surgical site bleeding (18.6%). With respect to documentation, 32.8% of medical record numbers were absent, 11.8% had name errors, and 2.2% of patients could not be identified. CONCLUSIONS: This is the first study to analyze the management and reporting of patient calls by otolaryngology residents. A wide array of clinical concerns are triaged by phone conversations. The study has implications for both resident and patient education. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:E163-E170, 2018.

Monitoring of the posterior cricoarytenoid muscle represents another option for neural monitoring during thyroid surgery: Normative vagal and recurrent laryngeal nerve posterior cricoarytenoid muscle electromyographic data.

OBJECTIVE: Intraoperative neural monitoring (IONM) of laryngeal nerves using electromyography (EMG) is routinely performed using endotracheal tube surface electrodes adjacent to the vocalis muscles. Other laryngeal muscles such as the posterior cricoarytenoid muscle (PCA) are indirectly monitored. The PCA may be directly and reliably monitored through an electrode placed in the postcricoid region. Herein, we describe the method and normative data for IONM using PCA EMG. STUDY DESIGN: Retrospective review. METHODS: Data were reviewed retrospectively for thyroid and parathyroid surgery patients with IONM of laryngeal nerves from January to August 2016. Recordings of vocalis and PCA EMG amplitudes and latencies with stimulation of laryngeal nerves were obtained using endotracheal (ET) tube-based and postcricoid surface electrodes. RESULTS: Data comprised EMG responses in vocalis and PCA recording channels with stimulation of the vagus, recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve from 20 subjects (11 left, 9 right), as well as PCA EMG threshold data with RLN stimulation from 17 subjects. Mean EMG amplitude was 725.69 ± 108.58 microvolts (µV) for the ipsilateral vocalis and 329.44 ± 34.12 µV for the PCA with vagal stimulation, and 1,059.75 ± 140.40 µV for the ipsilateral vocalis and 563.88 ± 116.08 µV for the PCA with RLN stimulation. There were no statistically significant differences in mean latency. For threshold cutoffs of the PCA with RLN stimulation, mean minimum and maximum threshold intensities were 0.37 milliamperes (mA) and 0.84 mA, respectively. CONCLUSION: This study shows robust and reliable PCA EMG waveforms with direct nerve stimulation. Further studies will evaluate feasibility and application of the PCA electrode as a complementary quantitative tool in IONM. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:283-289, 2018.

Statin use and risk of skin cancer.

BACKGROUND: Statins are among the most commonly used medications in the United States, and statin use is associated with increased risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). However, previous studies are limited by lack of adjustment for important confounders. OBJECTIVE: Examine the relation between statins and skin cancer risk in the Nurses' Health Study and Health Professionals Follow-up Study. METHODS: Cox proportional hazards regression was used to evaluate associations. RESULTS: During follow-up (2000-2010), we documented 10,201 BCC, 1393 SCC, and 333 melanoma cases. History of high cholesterol level was not associated with risk of BCC (pooled multivariable-adjusted hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.00-1.09), SCC (HR, 0.95; 95% CI, 0.85-1.06), or melanoma (HR, 0.87; 95% CI, 0.64-1.19). Statin use was not associated with risk of BCC (HR, 1.04; 95% CI, 0.99-1.09]), SCC (HR, 1.08; 95% CI, 0.94-1.24), or melanoma (HR, 1.04; 95% CI, 0.78-1.38). There was a trend toward higher BCC risk with longer duration of statin use in men (P trend = .003) but not in women (P trend = .86). LIMITATIONS: Lack of treatment data. CONCLUSION: History of high cholesterol level was not associated with skin cancer risk. Longer duration of statin use was associated with a trend toward higher BCC risk in men.

Temporal bone computed tomography findings associated with feasibility of endoscopic ear surgery.

PURPOSE: There are no formal radiologic criteria to stratify patients for transcanal (TEES) or transmastoid endoscopic ear surgery for resection of cholesteatoma. We aim to determine 1) whether standard preoperative computed tomography (CT) findings are associated with the need for conversion to a transmastoid approach and 2) the amount of time added for conversion from TEES to transmastoid techniques. MATERIALS AND METHODS: Retrospective chart review of consecutive pediatric and adult cases of TEES for primary cholesteatoma from 2013 through 2015 (n=52). TEES cases were defined as endoscope-only procedures that did not require a transmastoid approach (n=33). Conversion cases were defined as procedures that began as TEES however, required conversion to a transmastoid approach due to the inability to complete cholesteatoma removal (n=19). Preoperative CT findings and total operating room (OR) times of TEES and conversion cases were compared. RESULTS: Preoperative CT scan characteristics that were associated with conversion included tegmen erosion (p=0.026), malleus erosion (p<0.001), incus erosion (p=0.009), mastoid opacification (p=0.009), soft tissue opacification extending into the aditus ad antrum (p=0.009) and into antrum (p=0.006). Total OR time for TEES cases was significantly shorter than conversion cases (median 143min versus 217min, p<0.001). CONCLUSIONS: Preoperative CT findings, notably extension of soft tissue in the aditus ad antrum, antrum and mastoid, are associated with need for conversion to transmastoid technique to achieve removal of cholesteatoma. Endoscope-only cases were significantly faster than cases that required conversion to a transmastoid approach.

Skin Pigmentation and Risk of Hearing Loss in Women.

Black individuals have a lower risk of hearing loss than do whites, possibly because of differences in cochlear melanocytes. Previous studies have suggested that darker-skinned individuals tend to have more inner ear melanin, and cochlear melanocytes are important in generating the endocochlear potential. We investigated the relationship between self-reported hearing loss and skin pigmentation by using hair color, skin tanning ability, and skin reaction to prolonged sun exposure as surrogate measures of pigmentation among 49,323 white women in the Nurses' Health Study. Cox proportional hazards regression models were used to adjust for potential confounders. During 1,190,170 person-years of follow-up (1982-2012), there was no association between risk of hearing loss and hair color (for black hair vs. red or blonde hair, multivariable-adjusted relative risk (RR) = 0.99, 95% confidence interval (CI): 0.90, 1.09), skin tanning ability (for dark tan vs. no tan, multivariable-adjusted RR = 0.98, 95% CI: 0.92, 1.05), skin reaction to prolonged sun exposure (for painful burn with blisters vs. practically no reaction, multivariable-adjusted RR = 1.01, 95% CI: 0.93, 1.08), or Fitzpatrick skin phototype (for type IV vs. type I, multivariable-adjusted RR = 0.99, 95% CI: 0.92, 1.05). In our cohort of white women, surrogates for skin pigmentation were not associated with risk of hearing loss.

Relationship between Surgically Treated Superior Canal Dehiscence Syndrome and Body Mass Index.

Objective Examine the association between body mass index (BMI) and superior canal dehiscence (SCD) among patients who have undergone surgical repair for superior canal dehiscence. Study Design Retrospective comparison study. Setting Neurotology tertiary care center. Subjects and Methods Retrospective review of consecutive adult patients evaluated at our institution for SCD syndrome between November 2006 and August 2015. A control group who underwent imaging within the same period for reasons other than SCD was also included. Patient demographics, weight, and height were examined. We performed multiple subgroup analyses to investigate the relationship of BMI, surgery vs no surgery, and correlation between patient BMI and SCD size. Results Of the 268 patients with SCD, 99 underwent surgery; 96 of these patients had complete medical records and were eligible for inclusion. Eighty-eight patients were noted to have arcuate eminence defects, and the mean BMI of this surgical cohort was 28.09 ± 5.26 kg/m2. Nonsurgically treated patients with SCD with available data (n = 94) had a mean BMI of 27.97 ± 6.95 kg/m2. A control group of 204 patients who underwent computed tomography for non-SCD-related causes was analyzed, of whom 155 had available data with a mean BMI of 27.91 ± 6.38 kg/m2. Conclusion We demonstrate that adult patients who undergo surgery for SCD are not obese (mean BMI <30), and size of dehiscence poorly correlates with BMI. Our observations call into question the proposed theory that patient weight is a risk factor for the development of symptomatic SCD involving the arcuate eminence.

The electrophysiology of thyroid surgery: electrophysiologic and muscular responses with stimulation of the vagus nerve, recurrent laryngeal nerve, and external branch of the superior laryngeal nerve.

OBJECTIVES/HYPOTHESIS: Correlation of physiologically important electromyographic (EMG) waveforms with demonstrable muscle activation is important for the reliable interpretation of evoked waveforms during intraoperative neural monitoring (IONM) of the vagus nerve, recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve (EBSLN) in thyroid surgery. STUDY DESIGN: Retrospective chart review. METHODS: Data were reviewed retrospectively for thyroid surgery patients with laryngeal nerve IONM from January to December, 2015. EMG responses to monopolar stimulation of the vagus/RLN and EBSLN were recorded in bilateral vocalis, cricothyroid (CTM), and strap muscles using endotracheal tube-based surface and intramuscular hook electrodes, respectively. Target muscles for vagal/RLN and EBSLN stimulation were the ipsilateral vocalis and CTM, respectively. All other recording channels were nontarget muscles. RESULTS: Fifty surgical sides were identified in 37 subjects. All target muscle mean amplitudes were significantly higher than in nontarget muscles. With vagal/RLN stimulation, target ipsilateral vocalis mean amplitude was 1,095.7 µV (mean difference range = -814.1 to -1,078 µV, P < .0001). For EBSLN stimulation, target ipsilateral CTM mean amplitude was 6,379.3 µV (mean difference range = -6,222.6 to -6,362.3 µV, P < .0001). Target muscle large-amplitude EMG responses correlated with meaningful visual or palpable muscular responses, whereas nontarget EMG responses showed no meaningful muscle activation. CONCLUSIONS: Target and nontarget laryngeal muscles are differentiated based on divergence of EMG response directly correlating with presence or absence of visual and palpable muscle activation. Low-amplitude EMG waveforms in nontarget muscles with neural stimulation can be explained by the concept of far-field artifactual waveforms and do not correspond to a true muscular response. The surgeon should be aware of these nonphysiologic waveforms when interpreting and applying IONM during thyroid surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:764-771, 2017.

Changes in electromyographic amplitudes but not latencies occur with endotracheal tube malpositioning during intraoperative monitoring for thyroid surgery: Implications for guidelines.

OBJECTIVES/HYPOTHESIS: During intraoperative neural monitoring (IONM) in thyroid and parathyroid surgery, endotracheal (ET) tube migration can result in a decrease in vocalis electromyographic (EMG) amplitude without a concordant latency elevation during stimulation of the recurrent laryngeal nerve (RLN). STUDY DESIGN: Retrospective review. METHODS: Data were reviewed retrospectively for thyroid and parathyroid surgery patients with IONM of the laryngeal nerves from January 2015 to December 2015. Recordings of vocalis EMG amplitudes and latencies with RLN stimulation were obtained with the neuromonitoring ET tube surface electrodes in optimal baseline position, with vertical displacement away from the vocalis, and with rotational change away from baseline. RESULTS: ET tube surface electrode EMG recordings were obtained with stimulation of seven left and three right RLNs in a total of 10 patients. Mean vocalis EMG amplitudes were reduced with vertical displacement 1 and 2 cm both inferior and superior to baseline and with rotational change (45° and 90° clockwise and counterclockwise, 180°), although amplitude change with 45° clockwise and 180° rotation did not meet statistical significance. Mean EMG latency values did not change significantly from baseline with either rotation or vertical displacement of the ET tube. CONCLUSIONS: An isolated decrease in EMG amplitude without concordant latency elevation should warrant re-evaluation of ET tube position during thyroid and parathyroid surgery and is in contrast to a combined event, with both EMG amplitude decrease and concordant latency increase, which is more suggestive of a true neuropraxic injury. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2182-2188, 2017.

Barriers to Surgical Care and Health Outcomes: A Prospective Study on the Relation Between Wealth, Sex, and Postoperative Complications in the Republic of Congo.

BACKGROUND: Approximately thirty percent of the global burden of disease is comprised of surgical conditions. However, five billion people lack access to surgery, with complex factors acting as barriers. We examined whether patient demographics predict barriers to care, and the relation between these factors and postoperative complications in a prospective cohort. METHODS: Participants included people presenting to a global charity in Republic of Congo with a surgical condition between August 2013 and May 2014. The outcomes were self-reported barrier to care and postoperative complications documented by medical record. Logistic regression was used to adjust for covariates. RESULTS: Of 1237 patients in our study, 1190 (96.2 %) experienced a barrier to care and 126 (10.2 %) experienced a postoperative complication. The most frequently reported barrier was cost (73 %), followed by lack of provider (8.2 %). Greater wealth was associated with decreased odds of cost as a barrier (OR 0.72 [0.57, 0.90]). Greater wealth (OR 1.52 [1.03, 2.25]) and rural home location (OR 3.35 [1.16, 9.62]) were associated with increased odds of no surgeon being available. Cost as a barrier (OR 2.82 [1.02, 7.77]), female sex (OR 3.45 [1.62, 7.33]), and lack of surgeon (OR 5.62 [1.68, 18.77]) were associated with increased odds of postoperative complication. Patient wealth was not associated with odds of postoperative complication. CONCLUSIONS: Barriers to surgery were common in Republic of Congo. Patient wealth and home location may predict barriers to surgery. Addressing gender disparities, access to providers, and patient perception of barriers in addition to removal of barriers may help maximize patient health benefits.

Association Between Benzodiazepine Receptor Agonists and Snoring Among Women in the Nurses' Health Study.

Importance: Snoring is highly prevalent among adults. The use of benzodiazepine receptor agonists is also common, with higher prevalence of use with more advanced age. Benzodiazepine receptor agonists cause muscle relaxation, which may affect muscle tone and airway dynamics and thereby increase snoring. Previous studies examining the association between use of benzodiazepine receptor agonists and snoring were underpowered to detect clinically meaningful differences or did not report the magnitude of association. Objective: To investigate the association between use of benzodiazepine receptor agonists and snoring in women. Design, Setting, and Participants: Women aged 62 to 86 years provided information on snoring and covariates of interest in the 2008 survey of the Nurses' Health Study, a cross-sectional cohort study of female registered nurses in the United States. Potential effect modification of the association between use of benzodiazepine receptor agonists and snoring by age, body mass index, waist circumference, smoking, alcohol consumption, and physical activity was explored. Logistic regression was used to adjust for potential confounders. Data analysis was conducted from November 2015 to March 2016. Main Outcomes and Measures: Self-reported habitual snoring, defined as a few nights a week or more. Results: Of 52 504 participants (mean [SD] age, 72.4 [6.7] years), 14 831 (28.2%) reported habitual snoring. There was a slightly higher prevalence of benzodiazepine receptor agonist use among habitual snorers (11.4%) compared with nonhabitual snorers (10.6%) (absolute difference, 0.8%; 95% CI, 0.2%-1.4%). After multivariable adjustment, use of benzodiazepine receptor agonists was not associated with snoring (odds ratio, 1.01; 95% CI, 0.95-1.07) compared with women who did not use benzodiazepine receptor agonists. Although there was no significant interaction with smoking, there were higher odds of snoring with use of benzodiazepine receptor agonists among current smokers (odds ratio, 1.34; 95% CI, 1.04-1.73). Conclusions and Relevance: Use of benzodiazepine receptor agonists is not associated with odds of snoring in middle-aged and elderly women.

3D-printed pediatric endoscopic ear surgery simulator for surgical training.

INTRODUCTION: Surgical simulators are designed to improve operative skills and patient safety. Transcanal Endoscopic Ear Surgery (TEES) is a relatively new surgical approach with a slow learning curve due to one-handed dissection. A reusable and customizable 3-dimensional (3D)-printed endoscopic ear surgery simulator may facilitate the development of surgical skills with high fidelity and low cost. Herein, we aim to design, fabricate, and test a low-cost and reusable 3D-printed TEES simulator. METHODS: The TEES simulator was designed in computer-aided design (CAD) software using anatomic measurements taken from anthropometric studies. Cross sections from external auditory canal samples were traced as vectors and serially combined into a mesh construct. A modified tympanic cavity with a modular testing platform for simulator tasks was incorporated. Components were fabricated using calcium sulfate hemihydrate powder and multiple colored infiltrants via a commercial inkjet 3D-printing service. RESULTS: All components of a left-sided ear were printed to scale. Six right-handed trainees completed three trials each. Mean trial time (n = 3) ranged from 23.03 to 62.77 s using the dominant hand for all dissection. Statistically significant differences between first and last completion time with the dominant hand (p < 0.05) and average completion time for junior and senior residents (p < 0.05) suggest construct validity. CONCLUSIONS: A 3D-printed simulator is feasible for TEES simulation. Otolaryngology training programs with access to a 3D printer may readily fabricate a TEES simulator, resulting in inexpensive yet high-fidelity surgical simulation.

Benign paroxysmal positional vertigo commonly occurs following repair of superior canal dehiscence.

OBJECTIVES/HYPOTHESIS: Repair of superior canal dehiscence (SCD) often results in the resolution of preoperative auditory and vestibular symptoms; however, many patients experience dizziness in the postoperative period. Postoperative dizziness may be the result of new-onset benign paroxysmal positional vertigo (BPPV). This study aims to investigate the prevalence of BPPV before and following SCD repair. STUDY DESIGN: Retrospective chart review at a tertiary care center. METHODS: Electronic medical records were reviewed for patients with a diagnosis of SCD syndrome (SCDS) between January 2002 and May 2015. Collected information included demographic data, incidence of BPPV diagnosed by Dix-Hallpike maneuver before and following surgery, operative technique, repair material, and the duration of time to BPPV onset. RESULTS: A total of 180 patients with a diagnosis of SCDS were identified: 84 patients underwent surgery (operated subjects) and 96 were observed (nonoperated, control group). In operated subjects, 20 of 84 (23.8%) developed BPPV following SCD repair versus 6.2% of nonoperated (P < 0.005). Benign paroxysmal positional vertigo lateralized to the operated side in all but one subject whose laterality was unknown (P < 0.0001). There were no associations of BPPV with surgical approach (P = 0.50) or repair material (P = 0.33). The majority of subjects (58%) were diagnosed with BPPV within 3 months of surgery. CONCLUSION: New-onset BPPV occurs commonly after SCD repair and may be the result of mobilized otoliths from inner ear pressure changes. Although the exact etiology of post-SCD repair BPPV remains unknown, postoperative dizziness is important to discuss with patients during preoperative counseling. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2092-2097, 2016.

Long-term prognosis and risk factors among patients with HPV-associated oropharyngeal squamous cell carcinoma.

BACKGROUND: A subset of patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV-OSCC) experience poor clinical outcomes. The authors of this report explored prognostic risk factors for overall survival (OS) and recurrence-free survival (RFS). METHODS: Patients with incident HPV-OSCC who received treatment at the Johns Hopkins Hospital between 1997 and 2008 and who had tissue available for HPV testing as well as demographic and clinicopathologic information (N = 176) were included. Tissue was tested for HPV by in situ hybridization (ISH) and/or p16 immunohistochemistry. Demographic and clinicopathologic information was extracted from medical records. RESULTS: In total, 157 of 176 patients (90%) with OSCC had HPV-associated disease (HPV-OSCC). In the patients with HPV-OSCC, the 3-year and 5-year OS rates were 93% (95% confidence interval [CI], 88%-98%) and 89% (95% CI, 81%-97%), respectively. Shorter survival was observed among older patients (hazard ratio [HR], 2.33 per 10-year increase; 95% CI, 1.05-5.16 per 10-year increase; P = .038), patients with advanced clinical T classification (HR, 5.78; 95% CI, 1.60-20.8; P = .007), and patients who were currently using tobacco (HR, 4.38; 95% CI, 1.07-18.0; P = .04). Disease recurrence was associated with advanced clinical T-classification (HR, 8.32; 95% CI, 3.06-23; P < .0001), current/former alcohol use (HR, 13; 95% CI, 1.33-120; P = .03), and unmarried status (HR, 3.28; 95% CI, 1.20-9.00; P = .02). Patients who remained recurrence free for 5 years had an 8.6% chance of recurrence by 10 years (1-sided 95% CI upper bound, 19%; P = .088). CONCLUSIONS: In this study, prognostic risk factors were identified for patients with HPV-OSCC. The observed recurrence rates between 5 years and 10 years after definitive therapy need to be validated in additional studies to determine whether extended cancer surveillance is warranted in this cancer population. Cancer 2013;119:3462-3471.. © 2013 American Cancer Society.

An updated prostate cancer staging nomogram (Partin tables) based on cases from 2006 to 2011.

OBJECTIVE: To update the 2007 Partin tables in a contemporary patient population. PATIENTS AND METHODS: The study population consisted of 5,629 consecutive men who underwent RP and staging lymphadenectomy at the Johns Hopkins Hospital between January 1, 2006 and July 30, 2011 and met inclusion criteria. Polychotomous logistic regression analysis was used to predict the probability of each pathologic stage category: organ-confined disease (OC), extraprostatic extension (EPE), seminal vesicle involvement (SV+), or lymph node involvement (LN+) based on preoperative criteria. Preoperative variables included biopsy Gleason score (6, 3+4, 4+3, 8, and 9-10), serum PSA (0-2.5, 2.6-4.0, 4.1-6.0, 6.1-10.0, greater than 10.0 ng/mL), and clinical stage (T1c, T2c, and T2b/T2c). Bootstrap re-sampling with 1000 replications was performed to estimate 95% confidence intervals for predicted probabilities of each pathologic state. RESULTS: The median PSA was 4.9 ng/mL, 63% had Gleason 6 disease, and 78% of men had T1c disease. 73% of patients had OC disease, 23% had EPE, 3% had SV+ but not LN+, and 1% had LN+ disease. Compared to the previous Partin nomogram, there was no change in the distribution of pathologic state. The risk of LN+ disease was significantly higher for tumours with biopsy Gleason 9-10 than Gleason 8 (O.R. 3.2, 95% CI 1.3-7.6). The c-indexes for EPE vs. OC, SV+ vs. OC, and LN+ vs. OC were 0.702, 0.853, and 0.917, respectively. Men with biopsy Gleason 4+3 and Gleason 8 had similar predicted probabilities for all pathologic stages. Most men presenting with Gleason 6 disease or Gleason 3+4 disease have <2% risk of harboring LN+ disease and may have lymphadenectomy omitted at RP. CONCLUSIONS: The distribution of pathologic stages did not change at our institution between 2000-2005 and 2006-2011. The updated Partin nomogram takes into account the updated Gleason scoring system and may be more accurate for contemporary patients diagnosed with prostate cancer.