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Objective: (1) Describe short and long-term opioid prescribing patterns and variation after common otolaryngologic procedures and (2) assess risk factors for chronic opioid use in this cohort., Study Design: Retrospective cohort., Setting: Optum's deidentified Integrated Claims-Clinical data set., Methods: An adult cohort of patients undergoing common otolaryngology procedures from 2010 to 2017 was identified. Associations between procedure and other covariates with any initial opioid prescription and continuous opioid prescriptions were assessed with multivariable modeling. Opioid use was defined as continuous if a new prescription was filled within 30 days of the previous prescription. A time-to-event analysis assessed continuous prescriptions from the index procedure to end of the last continuous opioid prescription., Results: Among a cohort of 19,819 patients undergoing predominately laryngoscopy procedures (12,721, 64.2%), 2585 (13.0%) received an opioid prescription with variation in receiving a prescription, daily dose, and total initially prescribed dose varying by procedure, patient demographics, provider characteristics, and facility type. Opioids were prescribed most frequently after tonsillectomy (45.4%) and least frequently after laryngoscopy with interventions (3.9%), which persisted in the multivariable models. Overall rates of continuous use at 180 and 360 days were 0.48% and 0.27%, respectively. Among patients receiving an initial opioid prescription, maintaining continuous prescriptions was associated with tonsillectomy procedures, age (adjusted hazard ratio [aHR]: 0.997 per year, 95% confidence interval [CI]: 0.993-0.999), opioid prescriptions 6 months preprocedure (aHR: 0.42, 95% CI: 0.37-0.47), and nonotolaryngology initial prescribers (aHRs: <1, P < .05)., Conclusion: There is substantial variation in initial prescribing practices and continuous opioid prescriptions after common Otolaryngology procedures, but the overall rate of maintaining a continuous prescription starting after these procedures is very low., Level of Evidence: Level 3., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Rapid mixing and precise timing are key for accurate biomedical assay measurement, particularly when the result is determined as the rate of a reaction: for example rapid immunoassay in which the amount of captured target is kinetically determined; determination of the concentration of an enzyme or enzyme substrate; or as the final stage in any procedure that involves a capture reagent when an enzyme reaction is used as the indicator. Rapid mixing and precise timing are however difficult to achieve in point-of-care devices designed for small sample volumes and fast time to result. By using centrifugal microfluidics and transposing the reaction surface from a chamber to a single mm-scale bead we demonstrate an elegant and easily manufacturable solution. Reagents (which may be, for example, an enzyme, enzyme substrate, antibody or antigen) are immobilised on the surface of a single small bead (typically 1-2 mm in diameter) contained in a cylindrical reaction chamber subjected to periodically changing rotational accelerations which promote both mixing and uniform mass-transfer to the bead surface. The gradient of Euler force across the chamber resulting from rotational acceleration of the disc, dΩ disc /dt, drives circulation of fluid in the chamber. Oscillation of Euler force by oscillation of rotational acceleration with period, T, less than that of the hydrodynamic relaxation time of the fluid, folds the fluid streamlines. Movement of the bead in response to the fluid and the changing rotational acceleration provides a dynamically changing chamber shape, further folding and expanding the fluid. Bead rotation and translation driven by fluid flow and disc motion give uniformity of reaction over the surface. Critical parameters for mixing and reaction uniformity are the ratio of chamber radius to bead radius, r chamber /r bead , and the product Tr chamber (dΩ disc /dt), of oscillation period and Euler force gradient across the fluid. We illustrate application of the concept using the reaction of horse radish peroxidase (HRP) immobilised on the bead surface with its substrate tetramethylbenzidine (TMB) in solution. Acceleration from rest to break a hydrophobic valve provided precise timing for TMB contact with the bead. Solution uniformity from reaction on the surface of the bead in volumes 20-50 uL was obtained in times of 2.5 s or less. Accurate measurement of the amount of surface-bound HRP by model fitting to the measured kinetics of colour development at 10 s intervals is demonstrated., (© 2024. The Author(s).)

Intracellular leucine aminopeptidases (PepA) are metalloproteases from the family M17. These enzymes catalyze peptide bond cleavage, removing N-terminal residues from peptide and protein substrates, with consequences for protein homeostasis and quality control. While general mechanistic studies using model substrates have been conducted on PepA enzymes from various organisms, specific information about their substrate preferences and promiscuity, choice of metal, activation mechanisms, and the steps that limit steady-state turnover remain unexplored. Here, we dissected the catalytic and chemical mechanisms of Pa PepA: a leucine aminopeptidase from Pseudomonas aeruginosa . Cleavage assays using peptides and small-molecule substrate mimics allowed us to propose a mechanism for catalysis. Steady-state and pre-steady-state kinetics, pH rate profiles, solvent kinetic isotope effects, and biophysical techniques were used to evaluate metal binding and activation. This revealed that metal binding to a tight affinity site is insufficient for enzyme activity; binding to a weaker affinity site is essential for catalysis. Progress curves for peptide hydrolysis and crystal structures of free and inhibitor-bound Pa PepA revealed that Pa PepA cleaves peptide substrates in a processive manner. We propose three distinct modes for activity regulation: tight packing of Pa PepA in a hexameric assembly controls substrate length and reaction processivity; the product leucine acts as an inhibitor, and the high concentration of metal ions required for activation limits catalytic turnover. Our work uncovers catalysis by a metalloaminopeptidase, revealing the intricacies of metal activation and substrate selection. This will pave the way for a deeper understanding of metalloenzymes and processive peptidases/proteases.

The present study evaluates submandibular skinfold (SMS) cutoff values to estimate excess weight for BMI and percentage body fat (%BF) among Chilean adolescents. The results show an optimal area under the cutoff curve value of 83% among girls and 91% in boys to estimate SMS concerning %BF and BMI. The SMS cutoff value estimating obesity by %BF was 10 mm among girls and 9 mm among boys, 10 mm among girls, and 7 mm among boys by BMI. Our results showed that SMS is significantly associated with anthropometric parameters for obesity.

Importance: Diagnostic delay can negatively affect patient outcomes in head and neck cancer (HNC). Neck mass and other symptoms of undiagnosed HNC may be treated with antibiotics, delaying diagnosis and treatment, despite current clinical practice guidelines., Objective: To investigate temporal trends, associated factors, and time from symptom onset to antibiotic prescribing before an HNC diagnosis., Design, Setting, and Participants: A retrospective cohort study was conducted using data obtained from a deidentified electronic health records data set from January 1, 2011, to December 31, 2018. Patients with HNC enrolled in the data set for at least 1 year before diagnosis date determined by either 1 inpatient encounter or first of 2 outpatient encounters within 6 months were included. Data analysis was conducted from May 1 to November 9, 2022., Exposure: Antibiotic prescription within 3 months before HNC diagnosis date., Main Outcomes and Measures: The primary outcome was days from the first documented symptom to HNC diagnosis., Results: The cohort included 7811 patients with HNC (4151 [53.1%] men, mean [SD] age, 60.2 [15.8] years). At least 1 antibiotic was prescribed for 1219 patients (15.6%) within 3 months before HNC diagnosis. This represented an increase over the 8.9% prescribing rate during the baseline period 12 to 9 months before diagnosis. The rate of antibiotic prescribing within 3 months before diagnosis did not change significantly over time (quarterly percent change, 0.49%; 95% CI, -3.06% to 4.16%). Patients receiving an antibiotic prescription within 3 months of an HNC diagnosis had a 21.1% longer time between symptom onset and HNC diagnoses (adjusted rate ratio [ARR], 1.21; 95% CI, 1.14-1.29). Compared with diagnosis by otolaryngologists, primary care/internal medicine physicians were most likely to prescribe antibiotics for patients who were diagnosed with a presenting symptom (adjusted prevalence ratio, 1.60; 95% CI, 1.27-2.02). In patients presenting with neck mass/swelling, those presenting with other symptoms were more likely to have longer intervals from symptom onset to diagnosis (ARR, 1.31; 95% CI, 1.08-1.59)., Conclusions and Relevance: The findings of this cohort study suggest there is an increased rate of antibiotic prescription in the 3 months before HNC diagnosis, which is associated with an increased time to diagnosis. These findings identify an area for improvement in HNC care and guidelines.

The exquisite sensitivity of Raman spectroscopy for detecting biomolecular changes in skin cancer has previously been explored; however, this mostly required analysis of excised tissue samples using bulky, immobile laboratory instrumentation. In this study, the technique was translated for clinical use with a portable Raman system and customized fiber optic probe and applied to differentiation of skin cancers from benign lesions and inflammatory dermatoses. The aim was to provide an easy-to-use, easy-to-manage assessment tool for clinicians to use in their daily patient examination routine to perform rapid Raman measurements of skin lesions in vivo. Using this system, >867 spectra were measured in vivo from 330 patients with a wide variety of different benign skin lesions (n = 603), inflammatory dermatoses (n = 140), and skin cancers (n = 124). Ethnicities represented were 70% European; 16% Asian; 6% Māori; 5% Pacific people; and 4% Middle East, Latin American, and African. Accurate differentiation of skin cancers from benign lesions and inflammatory dermatoses was achieved using partial least squares discriminant analysis, with area under curve for the receiver operator curves for external validation sets ranging from 0.916 to 0.958. This study shows evidence for robust clinical translation of Raman spectroscopy for rapid, accurate diagnosis of skin cancer., (© 2023 The Authors.)

Objective: Determine trends and survival implications of adjuvant systemic therapy use for lower risk head and neck cancer., Study Design: Retrospective cohort study., Setting: US National Cancer Database, 2010 to 2019., Methods: Patients with mucosal head and neck squamous cell carcinoma treated with surgery and postoperative radiation therapy were identified. Adjuvant systemic therapy trends in those with and without extranodal extension or positive margins were assessed as annual percent change by JoinPoint analysis. Factors associated with adjuvant systemic therapy and overall survival were assessed with multivariable models and cox proportional hazard models, respectively., Results: From 2010 to 2019, approximately one-third of head and neck cancer patients without extranodal extension or positive margins received adjuvant systemic therapy. This rate decreased throughout the study period, with the highest annual percent change from 2016 to 2019 (12.21%; 95% confidence interval: 3.73%-19.95%). Younger age, male sex, Hispanic ethnicity, community program setting, advanced stage, and lymphovascular invasion increased the odds a patient would receive adjuvant systemic therapy. Adjuvant systemic therapy was associated with inferior overall survival when used in those without extranodal extension or positive margins after controlling for covariates., Conclusion: Though decreasing, adjuvant systemic therapy use is still common in the absence of extranodal extension and positive margins, and a variety of patient, provider, and oncologic factors may influence its use. The inferior overall survival after adjuvant systemic therapy in the absence of high-risk features suggests any oncologic benefit may not outweigh the costs and morbidity of the therapy., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

In this study, we utilize nanosecond and femtosecond direct laser writing for the generation of hydrophobic and hydrophilic microfluidic valves on a centrifugal microfluidic disk made of polycarbonate, without the need for wet-chemistry. Application of a femtosecond (fs) laser at 800 nm resulted in an increased contact angle, from ∼80° to ∼160°, thereby inducing the formation of a hydrophobic surface. In contrast, employing a nanosecond (ns) laser at 248 nm led to the formation of superhydrophilic surfaces. Morphological studies identified the enhancement in the surface roughness for the hydrophobic surfaces and the creation of smooth patterns for the hydrophilic surfaces. Chemical modifications in the laser-ablated samples were confirmed via Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis. These spectroscopic examinations revealed an increase of hydrophilic chemical groups on both surfaces, with a more pronounced increase on the nanosecond laser-modified surface. Furthermore, these surfaces were used as a case study for centrifugal microfluidic valves. These modified surfaces demonstrated peculiar pressure responses. Specifically, the hydrophobic valves necessitated a 29% increase in pressure for droplet passage through a microchannel. On the other hand, the superhydrophilic valves exhibited enhanced wettability, decreasing the pressure requirement for fluid flow through the modified area by 39%. However, similarly to the hydrophobic valves, the fluid exiting the hydrophilic valve area required an increased pressure. Overall, our study shows the potential for tailoring valve functionality in microfluidic systems through precise surface modifications using laser technology., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Uninsured individuals age 55-64 experience disproportionately poor outcomes compared to their insured counterparts. Adequate coverage may prevent these delays. This study investigates a "Medicare-effect" on head and neck squamous cell carcinoma (HNSCC) diagnosis and treatment., Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for persons ages 60-70 years in the United States from 2000 to 2016 with HNSCC. A "Medicare effect" was defined as an increase in incidence, reduction in advanced stage presentation, and/or decrease in cancer-specific mortality (CSM)., Results: Compared to their Medicaid or uninsured counterparts, patients age 65 have an increased incidence of HNSCC diagnosis, reduction in advanced stage presentation, decrease in cancer-specific mortality, and higher likelihood of receiving cancer-specific surgery., Conclusions: Patients age 65 with Medicare have decreased incidence of HNSCC, less hazard of late-stage diagnosis, and lower cancer-specific mortality than their Medicaid or uninsured counterparts, supporting the idea of a "Medicare effect" in HNSCC., (© 2023 Wiley Periodicals LLC.)

Photoinduced enhanced Raman spectroscopy (PIERS) is a new surface enhanced Raman spectroscopy (SERS) modality with a 680% Raman signal enhancement of adsorbed analytes over that of SERS. Despite the explosion in recent demonstrations, the PIERS mechanism remains undetermined. Using X-ray and time-resolved optical spectroscopies, electron microscopy, cyclic voltammetry, and density functional theory simulations, we elucidate the atomic-scale mechanism behind PIERS. Stable PIERS substrates were fabricated using self-organized arrays of TiO 2 nanotubes with controlled oxygen vacancy doping and size-controlled silver nanoparticles. The key source of PIERS vs SERS enhancement is an increase in the Raman polarizability of the adsorbed analyte upon photoinduced charge transfer. A balance between improved crystallinity, which enhances charge transfer due to higher electron mobility but decreases light absorption, and increased oxygen vacancy defect concentration, which increases light absorption, is critical. This work enables the rational design of PIERS substrates for sensing.

Background: There has been conflicting evidence on the independent prognostic role of human papillomavirus (HPV) status in sinonasal cancer. The objective of this study was to assess whether the survival of patients with sinonasal cancer differs based on various HPV statuses, including HPV-negative, positive for the high-risk HPV-16 and HPV-18 (HPV16/18) subtypes, and positive for other high-risk and low-risk HPV subtypes., Methods: In this retrospective cohort study, data from the National Cancer Database were extracted from the years 2010-2017 for patients who had primary sinonasal cancer (N = 12,009). The outcome of interest was overall survival based on HPV tumor status., Results: Study included an analytic cohort of 1070 patients with sinonasal cancer who had confirmed HPV tumor status (732 [68.4%] HPV-negative; 280 [26.2%] HPV16/18-positive; 40 [3.7%] positive for other high-risk HPV; and 18 [1.7%] positive for low-risk HPV). HPV-negative patients had the lowest all-cause survival probability at 5 years postdiagnosis (0.50). After controlling for covariates, HPV16/18-positive patients had a 37% lower mortality hazard than HPV-negative patients (adjusted hazard ratio, 0.63; 95% confidence interval [CI], 0.48-0.82). Patients aged 64-72 years (crude prevalence ratio, 0.66; 95% CI, 0.51-0.86) and 73 years and older (crude prevalence ratio, 0.43; 95% CI, 0.31-0.59) presented with lower rates of HPV16/18-positive sinonasal cancer than those aged 40-54 years. In addition, Hispanic patients had a 2.36 times higher prevalence of non-HPV16/18 sinonasal cancer than non-Hispanic White patients., Conclusions: These data suggest that, for patients with sinonasal cancer, HPV16/18-positive disease may confer a significant survival advantage compared with HPV-negative disease. Other high-risk and low-risk HPV subtypes have survival rates similar to the rates for HPV-negative disease. HPV status might be an important independent prognostic factor in sinonasal cancer that could be used in patient selection and clinical decisions., (© 2023 American Cancer Society.)

Prostate cancer (PCa) is a significant healthcare problem worldwide. Current diagnosis and treatment methods are limited by a lack of precise in vivo tissue analysis methods. Real-time cancer identification and grading could dramatically improve current protocols. Here, we report the testing of a thin optical probe using Raman spectroscopy (RS) and classification methods to detect and grade PCa accurately in real-time. We present the first clinical trial on fresh ex vivo biopsy cores from an 84 patient cohort. Findings from 2395 spectra measured on 599 biopsy cores show high accuracy for diagnosing and grading PCa. We can detect clinically significant PCa from benign and clinically insignificant PCa with 90% sensitivity and 80.2% specificity. We also demonstrate the ability to differentiate cancer grades with 90% sensitivity and specificity ≥82.8%. This work demonstrates the utility of RS for real-time PCa detection and grading during routine transrectal biopsy appointments., (© 2023 The Authors. Journal of Biophotonics published by Wiley-VCH GmbH.)

Objectives: Lymphoma, categorized as either non-Hodgkin's lymphoma or Hodgkin's lymphoma, is the second most common malignancy in the head and neck. Primary tongue lymphoma is exceedingly rare, with only case reports or small case series in the literature. This population-based analysis is the first to report the epidemiology and prognostic factors of survival in patients with primary tongue lymphoma., Methods: The Surveillance, Epidemiology, and End Results 18 database from the National Cancer Institute was queried for patients diagnosed between the years 2000 and 2016 with tongue lymphoma. Outcomes of interest were overall and disease-specific survival. Independent variables included age at diagnosis, sex, race, marital status, primary subsite, histologic subtype, stage, and treatment type., Results and Conclusion: Seven hundred forty patients met criteria; the male-female ratio was 1.5:1 and the mean age at diagnosis was 67.8 years. The majority of lesions localized to the base of tongue (90.0%), were histologically diffuse large B-cell lymphoma (59.5%), and presented at stage I or II (77.9%). Most early-stage lymphomas were treated with chemotherapy only (40.5%) or a combination of both chemotherapy and radiation (31.3%), while late-stage cancers were primarily treated with chemotherapy alone (68.5%). In multivariate analysis, younger age at diagnosis, female sex, married/partnered marital status, mucosa-associated lymphoid tissue histologic subtype, and earlier cancer stage were found to be associated with improved survival. Chemotherapy treatment with or without radiation was also associated with better survival compared to no treatment or radiation alone, though data regarding immunotherapy was unavailable.

Objectives: Identify which delivery modality for skin reconstruction care, face-to-face (FTF) in-person versus two telemedicine modalities, store-and-forward (S&F) and live video chat (LVC), is patient preferred and how cost, access, wait time, and demographics influence this preference., Study Design: Cross-sectional survey., Methods: A 16-question survey querying demographics and five scenario-specific preferences questions for the delivery of skin cancer reconstruction care was created and distributed via Amazon Mechanical Turk (MTurk), a crowdsourcing online marketplace, and in-person to Mohs micrographic surgery patients., Results: 1394 MTurk and 55 in-person responses were included. While 82.1% of online respondents prefer FTF clinic visits, this decreases to 58.3% with an in-person visit cost (p < 0.01) and furthermore to a minority 43.5% with both an in-person visit cost and wait time (p < 0.01) despite 77.8% believing that usefulness to the surgeon would improve FTF. Both the MTurk and in-person cohorts demonstrated similar response patterns despite considerable demographic differences. Multivariable analyses revealed that telemedicine was preferred by MTurk respondents with Medicaid (adjusted OR [95% CI]: 1.97 [1.18-3.31]) or Medicare (1.69 [1.10-2.59]) versus private insurance, and prior skin cancer (2.01 [1.18-3.42]) and less preferred by those earning $140,000+ per year (0.49 [0.29-0.82]) compared to those earning <$20,000 per year., Conclusions: FTF visits are preferred for skin cancer reconstruction care; this shifts toward virtual care with a cost and wait time in spite of the perceived quality of care. Individuals with socioeconomic barriers to access prefer telemedicine. MTurk can be a valuable tool for behavioral research in FPRS., Level of Evidence: NA Laryngoscope, 133:294-301, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

On the basis of their training, medical students are considered "the best case scenario" among university students in knowledge of the human papillomavirus (HPV). We evaluated differences in knowledge of HPV, HPV vaccine, and head and neck cancer (HNC) among medical students. A previously validated questionnaire was completed by 247 medical students at a Midwestern university. Outcomes of interest were knowledge score for HPV and HPV vaccine, and HNC, derived from combining questionnaire items to form HPV knowledge and HNC scores, and analyzed using multivariate linear regression. Mean scores for HPV knowledge were 19.4 out of 26, and 7.2 out of 12 for HNC knowledge. In the final multivariate linear regression model, sex, race, and year of study were independently associated with HPV and HPV vaccine knowledge. Males had significantly lower HPV vaccine knowledge than females (β = -1.53; 95% CI: -2.53, -0.52), as did nonwhite students (β = -1.05; 95% CI: -2.07, -0.03). There was a gradient in HPV vaccine knowledge based on the year of study, highest among fourth year students (β = 6.75; 95% CI: 5.17, 8.33). Results were similar for factors associated with HNC knowledge, except for sex. HNC knowledge similarly increased based on year of study, highest for fourth year students (β = 2.50; 95% CI: 1.72, 3.29). Among medical students, gaps remain in knowledge of HPV, HPV vaccine, and HPV-linked HNC. Male medical students have significantly lower knowledge of HPV. This highlights the need to increase medical student knowledge of HPV and HPV-linked HNC.

Objective: This study assesses longitudinal epidemiologic trends in the oldest head and neck cancer (HNC) patients, comparing the oropharynx to other mucosal HNC sites., Materials and Methods: Using data from the Surveillance, Epidemiology, and End Results database, trends in incidence, two-year cancer specific mortality, and percent of cases recommended for and which received surgery from 2000 to 2018 in patients ages ≥85 years were assessed using Joinpoint analysis by HNC site. Trends were quantified as annual percentage change (APC) with 95% confidence intervals (CI)., Results: Among older adults, oropharyngeal cancer (OPC) incidence increased (APC = 1.80% [95% CI: 0.94-2.67]), while mortality decreased (APC = -2.01% [95% CI: -3.26--0.74]) from 2000 to 2018. At other mucosal HNC sites, incidence and mortality remained stable. Percentage of patients who received surgery significantly changed for oropharyngeal (APC = -15.34% from 2000 to 2005 [95% CI: -24.37 to -4.79]) and laryngeal (APC = -4.61% from 2000 to 2008 [95% CI -8.28 to -0.80]) cancers. Trends in recommendation for surgery varied by site with significant decreases at the larynx, oral cavity, and oropharynx., Conclusion: OPC incidence is increasing among the oldest HNC patients. An increasing proportion of HPV-associated tumors could account for associated mortality improvement. There has been a shift towards non-surgical therapy possibly due to known favorable response of HPV-associated OPC to radiation therapy and/or poor surgical candidacy in this age group. The evolving treatment approach has not been detrimental to population-level survival outcomes, but optimal treatment has yet to be established. Future studies with pathologically confirmed HPV status are needed to better understand older adult OPC burden., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives/hypothesis: Radiation-associated sarcomas of the head and neck (RASHN) are known but rare sequelae after radiation for squamous cell carcinoma. The purpose of this study was to characterize RASHN, estimate the risk of RASHN in head and neck squamous cell patients after therapeutic radiation, and compare their survival to that of patients with de novo sarcomas of the head and neck (dnSHN)., Study Design: Retrospective database analysis., Methods: RASHN and dnSHN cases were collected from the Surveillance, Epidemiology, and End Results Database to identify risk factors and calculate incidence and latency. Survival was compared between RASHN and dnSHN., Results: The risk of RASHN was 20.0 per 100,000 person-years. The average latency period was 124.2 months (range 38-329). The cumulative incidence of RASHN at 20 years was 0.13%. Oral cavity and oropharynx primaries demonstrate increased risk. Five-year overall survival of RASHN was 22.4% compared to 64.5% for dnSHN., Conclusions: RASHN are confirmed to be rare. RASHN have poor overall survival and worse survival compared to dnSHN. The impact of intensity-modulated radiation therapy protocols on this risk is unknown. Modifiable risk factors of smoking and alcohol consumption continue to dwarf radiation therapy as risk factors of second primary head and neck cancers., Level of Evidence: 3 Laryngoscope, 132:1034-1041, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Raman spectroscopy has long been suggested as a potentially fast and sensitive method to monitor phytoplankton abundance and composition in marine environments. However, the pitfalls of visible detection methods in pigment-rich biological material and the complexity of their spectra have hindered their application as reliable in situ detection methods. In this study we combine 1064 nm confocal Raman spectroscopy with multivariate statistical analysis techniques (principle component analysis and partial leas-squares discriminant analysis) to reliably measure differences in the cell viability of a diatom species ( Chaetoceros muelleri ) and two haptophyte species ( Diacronema lutheri and Tisochrysis lutea ) of phytoplankton. The low fluorescence background due to this combined approach of NIR Raman spectroscopy and multivariate data analysis allowed small changes in the overall spectral profiles to be reliably monitored, enabling the identification of the specific spectral features that could classify cells as viable or nonviable regardless of their species. The most significant differences upon cell death were shown by characteristic shifts in the carotenoid bands at 1527 and 1158 cm -1 . The contributions from other biomolecules were less pronounced but revealed changes that could be identified using this combination of techniques., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Importance: Approximately 1 in 5 new patients with head and neck cancer (HNC) in the US belong to racial and ethnic minority groups, but their survival rates are worse than White individuals. However, because most studies compare Black vs White patients, little is known about survival differences among members of racial and ethnic minority groups., Objective: To describe differential survival and identify nonclinical factors associated with stage of presentation among patients with HNC belonging to racial and ethnic minority groups., Design, Setting, and Participants: This population-based retrospective cohort study used data from the 2007 to 2016 Surveillance, Epidemiology, and End Results (SEER) database and included non-Hispanic Black, Asian Pacific Islander, American Indian/Alaska Native, and Hispanic patients with HNC. The data were analyzed from December 2020 to May 2021., Main Outcomes and Measures: Outcomes were time to event measures: (HNC-specific and all-cause mortality) and stage of presentation. Covariates included nonclinical (age at diagnosis, sex, race and ethnicity, insurance status, marital status, and a composite socioeconomic status [SES]) and clinical factors (stage, cancer site, chemotherapy, radiation, and surgery). A Cox regression model was used to adjust associations of covariates with the hazard of all-cause death, and a Fine and Gray competing risks proportional hazards model was used to estimate associations of covariates with the hazard of HNC-specific death. A proportional log odds ordinal logistic regression identified which nonclinical factors were associated with stage of presentation., Results: There were 21 966 patients with HNC included in the study (mean [SD] age, 56.02 [11.16] years; 6072 women [27.6%]; 9229 [42.0%] non-Hispanic Black, 6893 [31.4%] Hispanic, 5342 [24.3%] Asian/Pacific Islander, and 502 [2.3%] American Indian/Alaska Native individuals). Black patients had highest proportion with very low SES (3482 [37.7%]) and the lowest crude 5-year overall survival (46%). After adjusting for covariates, Hispanic individuals had an 11% lower subdistribution hazard ratio (sdHR) of HNC-specific mortality (sdHR, 0.89; 95% CI, 0.83-0.95), 15% lower risk for Asian/Pacific Islander individuals (sdHR, 0.85; 95% CI, 0.78-0.93), and a trending lower risk for American Indian/Alaska Native individuals (sdHR, 0.85; 95% CI, 0.71-1.01), compared with non-Hispanic Black individuals. Race, sex, insurance, marital status, and SES were consistently associated with all-cause mortality, HNC-specific mortality, and stage of presentation, with non-Hispanic Black individuals faring worse compared with individuals of other racial and ethnic minority groups., Conclusions and Relevance: In this cohort study that included only patients with HNC who were members of racial and ethnic minority groups, Black patients had significantly worse outcomes that were not completely explained by stage of presentation. There may be unexplored multilevel factors that are associated with social determinants of health and disparities in HNC outcomes.

Importance: Patients with head and neck cancer (HNC) are known to be at increased risk of suicide compared with the general population, but there has been insufficient research on whether this risk differs based on patients' rural, urban, or metropolitan residence status., Objective: To evaluate whether the risk of suicide among patients with HNC differs by rural vs urban or metropolitan residence status., Design, Setting, and Participants: This cross-sectional study uses data from the Surveillance, Epidemiology, and End Results database on patients aged 18 to 74 years who received a diagnosis of HNC from January 1, 2000, to December 31, 2016. Statistical analysis was conducted from November 27, 2020, to June 3, 2021., Exposures: Residence status, assessed using 2013 Rural Urban Continuum Codes., Main Outcomes and Measures: Death due to suicide was assessed by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes (U03, X60-X84, and Y87.0) and the cause of death recode (50220). Standardized mortality ratios (SMRs) of suicide, assessing the suicide risk among patients with HNC compared with the general population, were calculated. Suicide risk by residence status was compared using Fine-Gray proportional hazards regression models., Results: Data from 134 510 patients with HNC (101 142 men [75.2%]; mean [SE] age, 57.7 [10.3] years) were analyzed, and 405 suicides were identified. Metropolitan residents composed 86.6% of the sample, urban residents composed 11.7%, and rural residents composed 1.7%. The mortality rate of suicide was 59.2 per 100 000 person-years in metropolitan counties, 64.0 per 100 000 person-years in urban counties, and 126.7 per 100 000 person-years in rural counties. Compared with the general population, the risk of suicide was markedly higher among patients with HNC in metropolitan (SMR, 2.78; 95% CI, 2.49-3.09), urban (SMR, 2.84; 95% CI, 2.13-3.71), and rural (SMR, 5.47; 95% CI, 3.06-9.02) areas. In Fine-Gray competing-risk analyses that adjusted for other covariates, there was no meaningful difference in suicide risk among urban vs metropolitan residents. However, compared with rural residents, residents of urban (subdistribution hazard ratio, 0.52; 95% CI, 0.29-0.94) and metropolitan counties (subdistribution hazard ratio, 0.55; 95% CI, 0.32-0.94) had greatly lower risk of suicide., Conclusions and Relevance: The findings of this cross-sectional study suggest that suicide risk is elevated in general among patients with HNC but is significantly higher for patients residing in rural areas. Effective suicide prevention strategies in the population of patients with HNC need to account for rural health owing to the high risk of suicide among residents with HNC in rural areas.

We examined the association between sexual orientation and human papillomavirus (HPV)-related risky sexual behaviors among high school students in the U.S. We used the 2015 Youth Risk Behavior Survey, a three-stage cluster sample, nationally representative, cross-sectional study. Participants were sexually active students (Grades 9-12) in public, private, and Catholic schools in 50 states and the District of Columbia (n = 5,958). Sexual orientation dimensions were: sexual self-identity (heterosexual, gay, lesbian, bisexual, and not sure) and sex of sexual contacts. HPV-associated risky sexual risk behaviors selected a priori were early sexual debut (≤ 12 or  ≥ 13 years old) and number of lifetime partners (≥ 2 or  ≥ 4). Separate multiple logistic regression analyses estimated association between sexual orientation and sex of sexual contacts, and HPV-associated risky sexual behaviors. Among the 5,958 high school students, a quarter had ≥ 4, and two-thirds had ≥ 2 sexual partners. Students who self-identified as bisexual (aOR = 2.43, 99% CI 1.19-4.98) or "not sure" (aOR = 4.56, 99% CI 2.54-8.17) were more likely to have sexual debut before 13 years. Similarly, students whose sexual contacts were adolescent females who had sex with females and males were more likely to have sexual debut before they turned 13 years of age (aOR = 3.46, 99% CI 1.83-6.48), or had ≥ 4 sexual partners (aOR = 2.66, 99% CI 1.74-4.08), or had ≥ 2 sexual partners (aOR = 3.09, 99% CI 1.91-5.00). In conclusion, HPV-associated risky sexual behavior is prevalent among high school students, especially sexual minorities. Interventions tailored to this population could increase HPV vaccine uptake and prevent future HPV-associated cancers and other negative outcomes., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Privately insured patients with head and neck cancer (HNC) typically have better outcomes; however, differential outcome among Medicaid versus the uninsured is unclear. We aimed to describe outcome disparities among HNC patients uninsured versus on Medicaid., Methods: A cohort of 18-64-year-old adults (n = 57 920) with index HNC from the Surveillance, Epidemiology, and End Results 18 database (2007-2015) was analyzed using Fine and Gray multivariable competing risks proportional hazards models for HNC-specific mortality., Results: Medicaid (sdHR = 1.65, 95% CI 1.58, 1.72) and uninsured patients (sdHR = 1.55, 95% CI 1.46, 1.65) had significantly greater mortality hazard than non-Medicaid patients. Medicaid patients had increased HNC mortality hazard than those uninsured., Conclusion: Compared with those uninsured, HNC patients on Medicaid did not have superior survival, suggesting that there may be underlying mechanisms/factors inherent in this patient population that could undermine access to care benefits from being on Medicaid., (© 2021 Wiley Periodicals LLC.)

HNO is a highly reactive molecule that shows promise in treating heart failure. Molecules that rapidly release HNO with precise spatial and temporal control are needed to investigate the biology of this signaling molecule. (Hydroxynaphthalen-2-yl)methyl-photocaged N -hydroxysulfonamides are a new class of photoactive HNO generators. Recently, it was shown that a (6-hydroxynaphthalen-2-yl)methyl (6,2-HNM)-photocaged derivative of N -hydroxysulfonamide incorporating the trifluoromethanesulfonamidoxy group ( 1 ) quantitatively generates HNO. Mechanistic studies have now been carried out on this system and reveal that the ground state protonation state plays a key role in whether concerted heterolytic C-O/N-S bond cleavage to release HNO occurs versus undesired O-N bond cleavage. N -Deprotonation of 1 can be achieved by adding an aqueous buffer or a carboxylate salt to an aprotic solvent. Evidence is presented for C-O/N-S bond heterolysis occurring directly from the singlet excited state of the N -deprotonated parent molecule on the picosecond time scale, using femtosecond time-resolved transient absorption spectroscopy, to give a carbocation and 1 NO - . This is consistent with the observation of significant fluorescence quenching when HNO is generated. The carbocation intermediate reacts rapidly with nucleophiles including water, MeOH, or even (H)NO in the absence of a molecule that reacts rapidly with (H)NO to give an oxime.

Objectives: Human papillomavirus (HPV)-associated cancers account for about 9% of the cancer mortality burden in the United States; however, survival differs among sociodemographic factors. We determine sociodemographic and clinical variables associated with HPV-associated cancer survival., Methods: Data derived from the Surveillance, Epidemiology, and End Results 18 cancer registry were analyzed for a cohort of adult patients diagnosed with a first primary HPV-associated cancer (anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancers), between 2007 and 2015. Multivariable Fine and Gray proportional hazards regression models stratified by anatomic site estimated the association of sociodemographic and clinical variables and cancer-specific survival., Results: A total of 77 774 adults were included (11 216 anal, 27 098 cervical, 30 451 oropharyngeal, 2221 penile, 1176 vaginal, 5612 vulvar; average age = 57.2 years). The most common HPV-associated cancer was cervical carcinoma (58%) for females and oropharyngeal (81%) for male. Among patients diagnosed with anal/rectal squamous cell carcinoma (SCC), males had a higher risk of death than females. NonHispanic (NH) blacks had a higher risk of death from anal/rectal SCC, oropharyngeal SCC, and cervical carcinoma; and Hispanics had a higher risk of death from oropharyngeal SCC than NH whites. Marital status was associated with risk of death for all anatomic sites except vulvar. Compared to nonMedicaid insurance, patients with Medicaid and uninsured had higher risk of death from anal/rectal SCC, oropharyngeal SCC, and cervical carcinoma., Conclusions: There exists gender (anal) and racial and insurance (anal, cervical, and oropharyngeal) disparities in relative survival. Concerted efforts are needed to increase and sustain progress made in HPV vaccine uptake among these specific patient subgroups, to reduce cancer incidence.

Bone strength in human cortical bone is determined by the composition and structure of both the mineral and collagen matrices and influenced by factors such as age, gender, health, lifestyle and genetic factors. Age-related changes in the bone matrix are known to result in loss of mechanical strength and increased fragility. In this study we show how Raman spectroscopy, with its exquisite sensitivity to the molecular structure of bone, reveals new insights into age- and sex-related differences. Raman analysis of 18 samples of cortical hip bone obtained from people aged between 47-82 years with osteoarthritis (OA) found subtle changes in the lipid and collagen secondary structure, and the carbonate (CO 3 2- ) and phosphate (PO 4 3- ) mineral ratios in the bone matrix. Significant differences were observed between older and younger bones, and between older female and older male bones; no significant differences were observed between younger male and female bones. Older female bones presented the lowest mineral to matrix ratios (MMR) and highest CO 3 2- /PO 4 3- ratios, and relative to lipid/collagen -CH 2 deformation modes at 1450 cm -1 they had lowest overall mineral content, higher collagen cross linking and lipid content but lower levels of α-helix collagen structures than older male and younger male and female bones. These observations provided further insight on bone composition changes observed in the bone volume fraction (BV/TV) for the older female bones from microCT measurements on the same samples, while tissue mineral density (TMD) measurements had shown no significant differences between the samples.

The emergence of the human papillomavirus (HPV) as the primary etiology of oropharyngeal cancer has changed head and neck cancer (HNC) epidemiology. This study described change in the age at diagnosis of oropharyngeal and non-oropharyngeal HNC in the United States in the last four decades. Using a retrospective cohort analysis, the Surveillance, Epidemiology, and End Results dataset from 1975 to 2016 was queried for eligible adult cases of HNC, grouped as oropharyngeal ( n = 31,702) versus non-oropharyngeal ( n = 87,108). Age at diagnosis was compared by gender (female, male) using independent t-test, and by race/ethnicity (Hispanic, non-Hispanic black, non-Hispanic white, non-Hispanic other) using analysis of variance. Joinpoint regression estimated yearly increases/decreases in age of diagnosis by sex and race/ethnicity through annual percent changes (APC), which were summarized with average annual percent changes (AAPC). Mean age at diagnosis for oropharyngeal cancer was 60.3 years. While there was initially a decrease in age at diagnosis, a 0.37% annual increase occurred from 2002 to 2016 (APC = 0.37, 95% confidence interval (CI) 0.28, 0.45). For non-oropharyngeal cancer, mean age at diagnosis was 63.2 years, with a continuous increase in age at diagnosis throughout the study period (1975-2016 AAPC = 0.08, 95% CI 0.04, 0.12). Females had higher average age at diagnosis than males for both sites, while blacks (57.4 years for oropharyngeal cancer; 59.0 years for non-oropharyngeal) had the lowest age at diagnosis of all races/ethnicity. Age at diagnosis of oropharyngeal cancer has increased significantly since 2002, while non-oropharyngeal HNC has increased significantly in the last four decades.

Background: To describe sociodemographic factors associated with head and neck cancer (HNC) survival among patients with distant metastatic disease., Methods: We retrospectively analyzed national data for 2889 adult patients with metastatic HNC (2007-2015). We used Fine and Gray competing risks proportional hazard models, stratified by oropharyngeal cancer status, controlled for sociodemographic factors (age, sex, race/ethnicity, marital status, and insurance status), and accounted for multiple testing., Results: Median survival time was 11 months (15 months for patients married/partnered; 13 months for patients with non-Medicaid insurance; P < .01). Among patients with oropharyngeal cancer, being married/partnered was associated with lower mortality hazard (sdHR divorced/separated = 1.37, 97.5% confidence interval [CI] = 1.07, 1.75; and sdHR never married = 1.43, 97.5% CI = 1.14, 1.80), as was having non-Medicaid insurance (sdHR uninsured = 1.44, 97.5% CI = 1.02, 2.04)., Conclusions: Health insurance and marital status are sociodemographic factors associated with survival among HNC patients with distant metastatic disease, especially in oropharyngeal cases., (© 2020 Wiley Periodicals, Inc.)

Objective/hypothesis: Early diagnosis and stage at presentation, two prognostic factors for survival among patients with head and neck cancer (HNC), are significantly impacted by a patient's health insurance status. We aimed to assess the impact of the Patient Protection and Affordable Care Act (ACA) on stage at presentation across socioeconomic and demographic subpopulations of HNC patients in the United States., Study Design: Retrospective data analysis., Methods: The National Cancer Database, a hospital-based cancer database (2011-2015), was queried for adults aged 18-64 years and diagnosed with a malignant primary HNC. The outcome of interest was change in early-stage diagnoses between 2011-2013 (pre-ACA) and 2014-2015 (post-ACA) using logistic regression models., Results: A total of 91,137 HNC cases were identified in the pre-ACA (n = 53,726) and post-ACA (n = 37,411) years. Overall, the odds of early-stage diagnoses did not change significantly post-ACA (aOR = 0.97, 95 % CI 0.94, 1.00; p = 0.081). However, based on health insurance status, HNC patients with Medicaid were significantly more likely to present with early-stage disease post-ACA (aOR = 1.12, 95 % CI 1.03, 1.21; p = 0.007). We did not observe increased odds of early-stage presentation for other insurance types. Males were less likely to present with early-stage disease, pre- or post-ACA., Conclusions: We demonstrate a significant association between ACA implementation and increased early-stage presentation among Medicaid-enrolled HNC patients. This suggests that coverage expansions through the ACA may be associated with increased access to care and may yield greater benefits among low-income HNC patients., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Laser micromachining with ultrashort pulses has shown great promise for clean, safe surgical treatment of bone tissue. However, comparisons of performance and development of "best practice" have been hampered by the difficulty of comparing results across a wide variety of experimental approaches and under surgically irrelevant conditions (e.g., dried, dead bone). Using a femtosecond (fs) pulsed laser system (τ = 140 fs, repetition rate = 1 kHz, λ = 800 nm), a comprehensive study of femtosecond laser microsurgery using the standard metrics of laser micromachining (ablation threshold, incubation effects, ablation rates, effect of focal point depth within the material and heat affected zone (HAZ)) was conducted on live, freshly harvested bovine and ovine cortical bone. Three important points of optimism for future implementation in the surgical theatre were identified: (1) the removal of material is relatively insensitive to the focal point depth within the material, removing the need for extreme depth precision for excellent performance; (2) femtosecond laser ablation of fresh bone demonstrates very little incubation effect, such that multiple passes of the laser over the same region of bone removes the same amount of material; and (3) the complete absence of collateral damage, heat- or shock-induced, on both the macro- and microscopic scales can be achieved readily, within a broad parameter range. Taken together, these results indicate a handheld or robotic deployed fiber laser platform for femtosecond laser microsurgery is a very viable prospect.

Objective: To describe comorbidity burden and nonclinical factors associated with all-cause mortality of sinonasal cancer in the United States., Methods: The National Cancer Database (2004-2013) was queried for adult cases of sinonasal cancer (n = 10,518). Outcome of interest was all-cause mortality. Independent variables included comorbidity score and nonclinical factors such as age, gender, race, facility type, distance to facility, insurance, and income. Survival analysis was conducted via multivariable extended Cox regression with Heaviside adjustments., Results: Patients were mostly (79%), male (61%), and mean age of diagnosis was 63.5 years. Approximately one in five patients (18.7%) had a major comorbid condition (Charlson-Deyo score ≥ 1) at diagnosis. After adjusting for clinical factors, increasing comorbidity score was associated with a corresponding increase in hazard of mortality (aHR comorbidity score of 1 = 1.25; 95% CI, 1.16, 1.35), (aHR score of 2+ = 1.61; 95%, CI 1.41, 1.83). Hazard of mortality was also associated with being male (aHR = 1.11; 95% CI, 1.04, 1.17); black (aHR = 1.13, 95% CI, 1.03, 1.24); uninsured (aHR = 1.45; 95% CI, 1.25, 1.68) or on Medicaid (aHR = 1.50; 95% CI, 1.33, 1.69); residence in zip codes with lower median income quartile (aHR < $30,000 = 1.17; 95% CI, 1.06, 1.29); and treatment at community cancer programs (aHR = 1.14, 95% CI 1.01, 1.28)., Conclusion: Comorbid disease is associated with all-cause sinonasal cancer mortality, and after accounting for known clinical factors, significant differences in mortality persist based on disparity-driven, nonclinical factors., Level of Evidence: NA Laryngoscope, 130:1443-1449, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The current study was conducted to determine whether the incidence of late-stage head and neck cancer (HNC) is decreasing and to estimate the risk of late-stage HNC diagnosis based on race and sex., Methods: Age-adjusted incidence rates for patients aged ≥18 years with stage IV HNC were abstracted from the Surveillance, Epidemiology, and End Results database (2004-2015). Rates were stratified by race, sex, and age. Joinpoint regression estimated annual percent changes (APCs) in rates over time, and logistic regression estimated adjusted odds ratios (aORs)., Results: There were 57,118 patients with stage IV HNC in the current study cohort, with an average age of 61.9 years. From 2004 to 2015, the age-adjusted incidence rates for stage IV HNC significantly increased by 26.1% (6.11 per 100,000 person-years in 2004 to 7.70 per 100,000 person-years in 2015). White and Asian/Pacific Islander/American Indian/Alaska Native patients had significant increases in incidence (APC for white patients, 3.03 [P < .01] and APC for other races, 1.95 [P < .01]), whereas rates among black patients remained stable but were highest across racial groups. Incidence was higher among males compared with females. When restricted only to patients with stage IVC (metastatic) HNC, there remained a significant increase in incidence, especially for oropharyngeal cancer, which showed a 22.9% increase (0.21 per 100,000 person-years in 2004 vs 0.25 per 100,000 person-years in 2015). Despite a decreasing overall incidence of stage IV HNC in black patients (aOR, 1.28; 95% CI, 1.22-1.34) they, along with males (aOR, 3.95; 95% CI, 3.80-4.11), had significantly increased risks of being diagnosed with late-stage HNC., Conclusions: There is an increasing incidence of late-stage HNC in the United States, with male patients and black individuals faring the worst., (© 2019 American Cancer Society.)

Objective: To determine sociodemographic factors associated with occupational, recreational and firearm-related noise exposure., Methods: This nationally representative, multistage, stratified, cluster cross-sectional study sampled eligible National Health and Nutrition Examination Survey participants aged 20-69 years (n = 4675) about exposure to occupational and recreational noise and recurrent firearm usage, using a weighted multivariate logistic regression analysis., Results: Thirty-four per cent of participants had exposure to occupational noise and 12 per cent to recreational noise, and 13 per cent repeatedly used firearms. Males were more likely than females to have exposure to all three noise types (adjusted odds ratio range = 2.63-14.09). Hispanics and Asians were less likely to have exposure to the three noise types than Whites. Blacks were less likely than Whites to have occupational and recurrent firearm noise exposure. Those with insurance were 26 per cent less likely to have exposure to occupational noise than those without insurance (adjusted odds ratio = 0.74, 95 per cent confidence interval = 0.60-0.93)., Conclusion: Whites, males and uninsured people are more likely to have exposure to potentially hazardous loud noise.

Background: Since the number of cancer survivors is increasing, it is imperative that we better understand the long-term consequences of these survivors. We assessed the risk of developing a second primary malignant neoplasm (SPMN) after an index potentially-HPV-associated cancers (P-HPV-AC)., Methods: We constructed a population-based cohort of patients with P-HPV-AC using Surveillance, Epidemiology, and End Results registry data (2000-2015). We limited patients to those with invasive P-HPV-AC [cervical, vagina, vulva, penile, anal, and oropharynx] based on the International Classification of Diseases for Oncology, 3rd edition. Excess SPMN risks were calculated based on standardized incidence ratios (SIRs) and excess absolute risks (EARs) per 10,000 person-years at risk (PYR)., Results: A total of 105,644 patients with an index P-HPV-AC were identified, and 7.8 % developed a SPMN. In all P-HPV-AC patients, the overall SIR was 1.73 (95 % CI: 1.69-1.77) and EAR of 70.72 per 10,000 PYR. All index P-HPV-AC sites showed statistically significant increases in the risk of SPMN, except for anal cancer among men, compared with the general population. The greatest increase in risk of SPMN was observed among patients diagnosed with an index P-HPV-oropharyngeal cancer (SIR = 1.83; 95 % CI, 1.70-1.82 and SIR = 2.29; 95 % CI, 2.12-2.47 for men and women, respectively). Men developed SPMN mostly in aero-digestive tract whiles women developed SPMN both in aero-digestive tract and other HPV-associated cancer sites., Conclusions: P-HPV-AC survivors experienced excess risk of SPMN. These findings have the potential to affect future surveillance practices and improve preventive healthcare for survivors of P-HPV-ACs., Competing Interests: Declaration of Competing Interest Dr. Warner Huh declare the following: DSMB (Chair): Inovio. All other authors have no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Incidence trends and outcomes of head and neck cancer (HNC) among female patients are not well understood. The objective of this study was to estimate incidence trends and quantify the association between health insurance status, stage at presentation, and survival among females with HNC., Study Design: Retrospective cohort study., Methods: The Surveillance, Epidemiology, and End Results database (2007-2014) was queried for females aged ≥18 years diagnosed with a malignant primary head and neck cancer (HNC) (n = 18,923). Incidence trends for stage at presentation were estimated using Joinpoint regression analysis. The association between health insurance status and stage at presentation on overall and disease-specific survival was estimated using Fine and Gray proportional hazards models., Results: Incidence of stage IV HNC rose by 1.24% from 2007 to 2014 (annual percent change = 1.24, 95% CI 0.30, 2.20). Patients with Medicaid (adjusted odds ratio [aOR] = 1.59, 95% confidence interval [CI] 1.45, 1.74) and who were uninsured (aOR = 1.73, 95% CI 1.47, 2.04) were more likely to be diagnosed with advanced stage (stages III/IV) HNC. Similarly, patients with Medicaid (adjusted hazard ratio [aHR] = 1.47, 95% CI 1.38, 1.56) and who were uninsured (aHR =1.45, 95% CI 1.29, 1.63) were more likely to die from any cause compared to privately insured patients. Medicaid (aHR = 1.34, 95% CI 1.24, 1.44) and uninsured (aHR = 1.41, 95% CI 1.24, 1.60) patients also had a greater hazard of HNC-specific deaths compared to privately insured patients., Conclusions: Incidence of advanced-stage presentation for female HNC patients in the United States has increased significantly since 2007, and patients who are uninsured or enrolled in Medicaid are more likely to present with late stage disease and die earlier., Level of Evidence: NA Laryngoscope, 130:385-391, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: Melanoma is one of the most common cancers worldwide, typically diagnosed in older adults. There is an increasing incidence in the younger population (age ≤40 years) in America. In addition, approximately 1 in 5 cases of melanoma affect the head and neck. However, there are limited data on the incidence of head and neck melanoma in the pediatric, adolescent, and young adult population in North America (United States and Canada)., Objective: To assess 20-year demographic and incidence changes associated with head and neck melanoma in the pediatric, adolescent, and young adult population in North America., Design, Setting, and Participants: A descriptive analysis of retrospective data on head and neck melanoma from the North American Association of Central Cancer Registries' Cancer in North America public use data set from 1995 to 2014 was conducted. The data set currently includes 93% of the United States and 64% of the Canadian populations. Eligible data were from 12 462 pediatric, adolescent, and young adult patients (aged 0-39 years) with a confirmed diagnosis of melanoma (International Classification of Diseases-Oncology 3 histologic types 8720-8790) in primary head and neck sites: skin of lip, not otherwise specified (C44.0); eyelid (C44.1); external ear (C44.2); skin of other/unspecified parts of face (C44.3); and skin of scalp and neck (C44.4). The study was conducted from January 26 to July 21, 2019., Main Outcomes and Measures: Log-linear regression was used to estimate annual percentage change in age-adjusted incidence rates (AAIRs) of head and neck melanoma., Results: Of the 12 462 patients with head and neck melanoma included in the study, 6810 were male (54.6%). The AAIR was 0.51 per 100 000 persons (95% CI, 0.50-0.52 per 100 000 persons). In North America, the incidence of head and neck melanoma increased by 51.1% from 1995 to 2014. The rate was higher in the United States (AAIR, 0.52; 95% CI, 0.51-0.53 per 100 000 person-years) than Canada (AAIR, 0.43; 95% CI, 0.40-0.45 per 100 000 persons). In the United States, the incidence increased 4.68% yearly from 1995 to 2000 and 1.15% yearly from 2000 to 2014. In Canada, the incidence increased 2.18% yearly from 1995 to 2014. Male sex (AAIR, 0.55; 95% CI, 0.54-0.57 per 100 000 persons), older age (AAIR, 0.79; 95% CI, 0.79-0.80 per 100 000 persons), and non-Hispanic white race/ethnicity (AAIR, 0.79; 95% CI, 0.77-0.80 per 100 000 persons) were associated with an increased incidence of head and neck melanoma., Conclusions and Relevance: The incidence of pediatric, adolescent, and young adult head and neck melanoma in North America appears to have increased by 51.1% in the past 2 decades, with males aged 15 to 39 years the main cohort associated with the increase.

Annually, about 16,500 HPV-associated cancers occur in the US among men. Data regarding HPV vaccine uptake among men based on nativity status (i.e., US-versus foreign-born) is limited, yet potentially important for informing interventions. We assessed differences in HPV vaccine uptake by nativity status among men aged 18-34 years in the US. The 2014-2017 National Health Interview Survey was examined for men, aged 18-34 years (n = 14,056). HPV vaccine initiation was defined as receipt of at least one dose of the vaccine and completion as receipt of three doses. Weighted, multivariable binary logistic regression models were used to assess the association between nativity status and HPV vaccine uptake, adjusting for demographic, socioeconomic, and healthcare factors. Analyses were performed in July 2018. Overall, 17% of men self-identified as foreign-born, 9.9% of men had initiated the HPV vaccine, and 3.3% had completed the HPV vaccine. Among foreign-born men, Asians had the highest HPV vaccination rates whereas those from Indian subcontinental region had the lowest rates. After accounting for demographic, socioeconomic, and healthcare factors, compared to US-born men, foreign-born men were 46% (adjusted odds ratio = 0.54; 95% CI = 0.39-0.72) less likely to initiate the HPV vaccine but there was no difference between the two groups in terms of vaccine completion. We found that HPV vaccine uptake among men was very low overall, and foreign-born men had lower initiation compared to US-born men. Public health interventions which improve HPV vaccination need to be developed for all men, irrespective of nativity status., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2019 The Authors.)

Objective: The 'Astrocytic Network' is an emerging research field for researchers in cell biology. Culturing astrocytes in organised networks is a novel method for permitting controlled studies and investigations into the calcium transients of such networks. Recent research has photolithographically patterned hNT astrocytes on parylene-C inlayed SiO 2 trench grid networks. However, it was observed that the trench networks could not specifically immobilise the astrocyte cell bodies to the nodes of the networks., Approach: In this study, for the first time, we demonstrate how it is possible to establish grid networks of human hNT astrocytes on raised parylene-C structures where the cell bodies are specifically organised down to the single-cell level on nodes of the grid and connected throughout., Main Results: Here, we report these to be the largest patterned single-cell grid network of astrocytes of their kind consisting of 100 cells in a 10  ×  10 grid arrangement to an 80% efficiency. We quantify the level of patterning through six cell patterning assessment indices: the parylene adhesion index (PAI); SiO 2 attraction index (SAI); node index (NI) and connectivity interval (χI), number of components (k) and fielder value (λ ss ) and report that the best connected network is obtained with 65 µm node size, 90 µm node spacing, and 5 µm interconnecting track width (PAI  =  0.77  ±  0.040, SAI  =  0.12  ±  0.049, NI  =  0.81  ±  0.066, χI  =  0.25  ±  0.064, k  =  2.33  ±  1.528, λ ss   =  0.0249  ±  0.0018). We finally demonstrate, through delivery of ATP, that the networks are functional on the raised parylene-C grid structures., Significance: The significance of this study is that it determines the optimal dimensions to obtain highly organised, large, interlinked, single-cell networks which provide an effective platform to investigate calcium communication within astrocytic networks in an accurate, controlled and repeatable manner.

Draft genomes of the fungal species Fusarium xylarioides, Teratosphaeria gauchensis and T. zuluensis are presented. In addition an annotation of the genome of Ceratocystis fimbriata is presented. Overall these genomes provide a valuable resource for understanding the molecular processes underlying pathogenicity and potential management strategies of these economically important fungi., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

A multitude of simulator systems for endoscopic sinus surgery (ESS) are available as training tools for residents preparing to enter the operating room. These include human cadavers, virtual reality, realistic anatomic models, and low-fidelity gelatin molds. While these models have been validated and evaluated as independent tools for surgical trainees, no study has performed direct comparison of their outcomes. To address this deficiency, we aimed to evaluate the utility of high-fidelity and low-fidelity trainers as compared to a traditional control (no simulator exposure) for novice trainees acquiring basic ESS skills. Thirty-four first-year medical students were randomized to 3 groups and taught basic sinus anatomy and instrumentation. Two groups received training with either the high-fidelity or low-fidelity trainer, while 1 group served as control. These groups were then tested with cadaveric specimens. These sessions were recorded and graded by an expert. There was no statistical difference in performance between the 3 study groups with regard to identification of anatomy, endoscopic competency, or completion of basic tasks. When the high-fidelity and low-fidelity arms were grouped into a single "trained" cohort, they demonstrated significantly improved time to completion for basic anatomy ( P = .043) and total time ( P = .041). This is the first study to perform a direct comparison of performance between high-fidelity and low-fidelity ESS simulators and controls. Although we found no difference in performance of novice trainees with regard to basic anatomical identification or procedural tasks associated with ESS, the use of ESS simulators may improve time to completion.

Objectives/hypothesis: To 1) examine the characteristics of patients who develop second primary malignancies (SPMs) from an index human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) and HPV-unrelated HNSCC and to 2) compare overall survival between those with HPV-related and HPV-unrelated index HNSCC among patients who develop SPM., Study Design: Retrospective cohort analysis., Methods: A retrospective study was conducted of 113,259 patients who were diagnosed with HNSCC from 2000 to 2014. SPM was defined as the first subsequent primary cancer occurring at least 2 months after index cancer diagnosis, and HPV-relatedness was based on whether patients' index HNSCC was potentially HPV-related or HPV-unrelated. Multivariable Fine and Gray (FG) competing-risks regression models were used to estimate factors associated with risk of SPM by HPV-relatedness. Among patients with SPM, an adjusted Cox proportional hazards (PH) regression model was used to assess the association between HPV-relatedness and survival., Results: Approximately 13,900 patients (12.3%) developed SPM. In the FG model, patients with HPV-unrelated HNSCC had a 15% higher risk of developing SPM (adjusted hazard ratio: 1.15, 95% confidence interval: 1.10-1.20) than those with potentially HPV-related HNSCC, but the same characteristics were associated with SPM development. In the Cox PH model, patients with SPM whose index HNSCC was HPV-unrelated had higher risk of death than those whose index HNSCC was potentially HPV-related (adjusted hazard ratio: 1.06; 95% confidence interval: 1.02-1.11)., Conclusions: Patients with HPV-unrelated HNSCC have a higher risk of SPM development than do those with HPV-related HNSCC. Effective secondary disease-prevention strategies should be established to improve long-term patient outcomes., Level of Evidence: NA Laryngoscope, 129:1828-1835, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Thirty-day (30-day) mortality, a common posttreatment quality metric, is yet to be described following surgery for head and neck squamous cell carcinoma (HNSCC). This study aimed to measure 30-day postoperative mortality in HNSCC and describe clinical/nonclinical factors associated with 30-day mortality., Methods: In this retrospective cohort study, the National Cancer Database (2004 to 2013) was queried for eligible cases of HNSCC (n=91,858). Adult patients were included who were treated surgically with curative intent for the primary HNSCC, not missing first treatment, survival, and follow-up information. The outcome of interest was all-cause mortality within 30 days of definitive surgery. Clinical and nonclinical factors associated with all-cause 30-day postoperative mortality were estimated using a fully adjusted, multivariable logistic regression, which accounted for time-varying nature of adjuvant therapy., Results: A total of 775 patients died within 30 days of definitive surgery for HNSCC (30-day mortality rate of 0.84%). Thirty-day mortality rate was however up to 2.33% (95% confidence interval [CI], 1.91%-2.75%) depending on comorbidity. In the fully adjusted model, increasing severity of comorbidity was associated with greater odds of 30-day mortality (Charlson-Deyo comorbidity scores of 1: adjusted odds ratio [aOR], 1.43; 95% CI, 1.21-1.69, and of 2+ aOR, 2.55; 95% CI, 2.07-3.14). Odds of 30-day mortality were greater among Medicaid patients (aOR, 1.77; 95% CI, 1.30-2.41), and in patients in neighborhoods with little education (≥ 29% missing high school diploma: aOR, 1.35; 95% CI, 1.02-1.78)., Conclusions: Patients with higher 30-day mortality were those with a greater burden of comorbidities, with little education, and covered by Medicaid.

While there are a growing number of cancer survivors, this population is at increased risk of developing second primary malignancies (SPMs). We described the incidence, most common tumor sites, and trends in burden of SPM among survivors of the most commonly diagnosed smoking-related cancers. The current study was a population-based study of patients diagnosed with a primary malignancy from the top 10 smoking-related cancer sites between 2000 and 2014 from Surveillance, Epidemiology, and End Results data. SPM risks were quantified using standardized incidence ratios (SIRs) and excess absolute risks (EARs) per 10,000 person-years at risk (PYR). Trends in the burden of SPM were assessed using Joinpoint regression models. A cohort of 1,608,607 patients was identified, 119,980 (7.5%) of whom developed SPM (76% of the SPMs were smoking-related). The overall SIR of developing second primary malignancies was 1.51 (95% CI, 1.50-1.52) and the EAR was 73.3 cases per 10,000 PYR compared to the general population. Survivors of head and neck cancer had the highest risk of developing a SPM (SIR = 2.06) and urinary bladder cancer had the highest excess burden (EAR = 151.4 per 10,000 PYR). The excess burden of SPM for all smoking-related cancers decreased between 2000 and 2003 (annual percentage change [APC] = -13.7%; p = 0.007) but increased slightly between 2003 and 2014 (APC = 1.6%, p = 0.032). We show that 1-in-12 survivors of smoking-related cancers developed an SPM. With the significant increase in the burden of SPM from smoking-related cancers in the last decade, clinicians should be cognizant of long-term smoking-related cancer risks among these patients as part of their survivorship care plans., (© 2019 UICC.)

Cell patterning is becoming increasingly popular in neuroscience because it allows for the control in the location and connectivity of cells. A recently developed cell patterning technology uses patterns of an organic polymer, parylene-C, on a background of SiO2. When cells are cultured on the parylene-C/SiO2 substrate they conform to the underlying parylene-C geometry. Parylene-C is, however, just one member of a family of parylene polymers that have varying chemical and physical properties. In this work, we investigate whether two commercially available mainstream parylene derivatives, parylene-D, parylene-N and a more recent parylene derivative, parylene-HT to determine if they enable higher fidelity hNT astrocyte cell patterning compared to parylene-C. We demonstrate that all parylene derivatives are compatible with the existing laser fabrication method. We then demonstrate that parylene-HT, parylene-D and parylene-N are suitable for use as an hNT astrocyte cell attractive substrate and result in an equal quality of patterning compared to parylene-C. This work supports the use of alternative parylene derivatives for applications where their different physical and chemical properties are more suitable., Competing Interests: The authors have declared that no competing interests exist.