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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, 2021.

Intracellular organelles play an essential role in regulating the biochemistry of various processes and events in eukaryotic cells. Understanding and quantifying their morphological dynamics should allow for their deeper analysis. However, the development of organelle and membrane tracking algorithms is challenging, especially in the case of studying the regulation of Golgi-derived membrane tubules, which show varied sizes and shapes, continuous fission and fusion events, and different directions of movement. Here we have sought to establish a tracking system for tubular subcellular structures, to characterize morphological changes in membrane fission and fusion events. The development of a tracking algorithm consists of two methods of particle linking: the k-nearest neighbor method applied to successive images with a high temporal resolution, and a modification method named fixed-lag interval smoothing Kalman filtering, for situations of temporary particle disappearance and forward and backward movement. The system shows excellent efficiency for tracking. One key advantage of this system is that it not only provides track mapping of tubules for fast and convenient interpretation, but also displays tubule labeling and the type of fission and fusion, with corresponding changes of events displayed in the track mapping view. Moreover, tracking measurements of event type and growth rate in length, motility, velocity, and diffusion features are calculated and saved offline use for further analysis. This prototype tracking system can be applied to different organelles undergoing fission and fusion events, e.g. Golgi-derived tubules and mitochondria, to help biologists quantify and better understand the mechanisms underlying changes in membrane dynamics.

Purpose of review This review explores trends in the United States (US) transplant surgery workforce with a focus on historical demographics, post-fellowship job market, and quality of life reported by transplant surgeons. Ongoing efforts to improve women and racial/ethnic minority representation in transplant surgery are highlighted. Future directions to create a transplant workforce that reflects the diversity of the US population are discussed. Recent findings Representation of women and racial and ethnic minorities among transplant surgeons is minimal. Although recent data shows an improvement in the number of Black transplant surgeons from 2% to 5.5% and an increase in women to 12%, the White to Non-White transplant workforce ratio has increased 35% from 2000 to 2013. Transplant surgeons report an average of 4.3 call nights per week and less than five leisure days a month. Transplant ranks 1st among surgical sub-specialties in the prevalence of three well-studied facets of burnout. Concerns about lifestyle may contribute to the decreasing demand for advanced training in abdominal transplantation by US graduates. Summary Minimal improvements have been made in transplant surgery workforce diversity. Sustained and intentional recruitment and promotion efforts are needed to improve the representation of women and minority physicians and advanced practice providers in the field.

We interrogated a students as partners (SaP), co-curricular program that focuses on supporting student learning. To center power and equity in SaP, the program was grounded in social design-based experiment methodology. We considered the manifestation of power and equity beyond higher education, to that of broader socio-political contexts. Collaborative autoethnography (CAE) was used to garner a richer understanding of student-staff experiences of the program. Through CAE, power emerged as central to our collective experiences, and a recognition that power asymmetry in students as partners programs is complex and multi-layered. We found that to address power imbalances in these programs requires considered strategies and intentional designs. Further, CAE, in and of itself, can be a powerful way to foster self-awareness, mutual trust, respect, and the acknowledgement of others in student-staff partnerships. We conclude by recommending the importance of deliberate design for equity and power towards consequential learning and transformational change.

Background Many studies have evaluated the effects that a lack of resources has in children’s physical and cognitive development. Although there are reviews that have focused on applied interventions from different perspectives, there is still a need for a comprehensive review of what has been attempted with these children from the cognitive intervention field. The aim of this paper is to present a protocol for a systematic review collecting randomized controlled trials (RCTs) studies whose purpose was to enhance cognitive development through the implementation of cognitive interventions in children and adolescents (< 18 years old) from low socioeconomic Status (SES) settings. Methods The following databases will be searched: Web of Science (WoS core collection), PsycINFO, Cochrane Central Register of Controlled Trial, ERIC, PubMed, ICTRP and Opengrey Register (System for Information of Grey Literature in Europe). Searches will be adapted for each database. Additionally, the reference list of articles included in the review will also be searched. As part of this process, two reviewers will determine, independently, the suitability of each article taking into account predefined inclusion/exclusion criteria. Pertinent data will then be extracted, including sample characteristics, specifics of the intervention, and outcomes, as well as follow-up measures. Internal validity will be assessed using the Cochrane Risk of Bias Tool. A quantitative synthesis of results will be conducted using a meta-analysis. However, if a meta-analysis is difficult to implement due to the diversity of the studies (for example, in terms of measures used to estimate the effect size, intervention types, outcomes, etc.), the technique synthesis without meta-analysis (SWiM) will be used. A description of outcome measures will be provided, as measured by validated neuropsychological instruments of any cognitive function. Discussion The systematic review will offer a framework based on evidence to organisations, institutions, and experts who want to implement or promote interventions aimed at enhancing cognitive domains in children and adolescents who live in disadvantaged contexts. Systematic review registration This protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 16 March 2020 (registration number: CDR42020150238).

Background: Reading comprehension is a complex process influenced by many factors. However, the abilities that are known to influence reading comprehension may not contribute equally for children with different levels of oral language. Aims: Here we examined the relationship of two factors known to influence reading comprehension (morphology and syntax) in a group of children who varied in their levels of oral vocabulary. Method: Two hundred seventy-three typically developing Spanish-speaking fourth graders were assessed on non-verbal intelligence, word and pseudoword reading, oral vocabulary, morphological awareness and syntax, along with reading comprehension ability. Standardised oral language scores within this group ranged from the first to the 99th percentile. Mediated multiple regression with moderation was used to assess (1) whether the influence of oral vocabulary on reading comprehension was mediated by decoding, morphology or syntax and (2) whether the effects of syntax on reading comprehension varied as a function of oral vocabulary levels. Results: There was a direct positive relationship between vocabulary and reading comprehension, and this was mediated by word reading and syntax, but not by pseudoword reading or morphology. Furthermore, the relation between syntax and reading comprehension was moderated by oral vocabulary such that the strength of this relationship diminished as oral vocabulary levels increased. Conclusions: These findings suggest that longitudinal research is necessary to explore the possibility that a syntax intervention might be beneficial for readers with low oral vocabulary. FEDER 2014-2020 Consejería de Economía, Conocimiento, Empresas y Universidad US-1264792

Non-directed living kidney donors (NDDs) are unique from the traditional directed living donors in terms of the circumstances that led NDDs to undergo a donation. The purpose of this study was to synthesize and discuss key similarities, differences, and existing gaps in the literature comparing their kidney donation process experiences and post-donation outcomes among directed and non-directed donors. A total of eight recent studies were reviewed as part of this study. These studies provided insights into the socioeconomic, physical, and mental health outcomes experienced by NDDs and directed donors throughout the various stages of the evaluation and donation process. Among the studies, NDDs were generally not found to demonstrate having substantial differences as compared to the traditional directed donor within the realms of physical and psychosocial health outcomes post-donation. However, NDDs did have fewer financial burdens as compared to directed donors, which may be related to the differences in demographic characteristics and the limited study sample sizes. Recent evidence on outcomes among non-directed living donors as compared with directed donors should inform efforts to enhance the evaluation and post-donation experiences for this special population. While future studies remain warranted, the current literature signals that further improvements can be made by revisiting the current evaluation screening protocols for living kidney donation as well as the donation system’s infrastructure to help yield enhanced outcomes and experiences among both directed and non-directed donors.

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.

ObjectiveTo determine sociodemographic factors associated with occupational, recreational and firearm-related noise exposure.MethodsThis 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.ResultsThirty-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).ConclusionWhites, males and uninsured people are more likely to have exposure to potentially hazardous loud noise.

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.

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

Extracellular vesicles (EVs) are small lipid-enclosed particles that can carry various types of cargo, including proteins, nucleic acids and metabolites. They are known to be released by all cell types and can be taken up by other cells, leading to the transfer of the cargo they carry. As such, they represent an important type of intercellular signalling and a natural mechanism for transferring macromolecules between cells. This ability to transfer cargo could be harnessed to deliver therapeutic molecules. Indeed, a growing body of work has described the attempt by the field to utilise EVs to deliver a range of therapeutics including RNAi, CRISPR/Cas9 and chemotherapeutics, to a specific target tissue. However, there are numerous barriers associated with the use of EVs as therapeutic vehicles, including the challenge of efficiently loading therapeutics into EVs, avoiding clearance of the EVs from circulation, targeting the correct tissue type and the inefficiency of internalisation and functional delivery of the cargo. Despite these difficulties, EVs represent a tremendous therapeutic opportunity, both for the delivery of exogenous cargo, as well as the therapeutic benefit of targeting aberrant EV signalling or treating patients with natural EVs, such as those released by mesenchymal stem cells. This review describes current knowledge on the therapeutic potential of EVs and the challenges faced by the field. Many of these challenges are due to a lack of complete understanding of EV function, but further research in this area should continue to yield new solutions that will lead to the use of EVs in the clinic.

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

This article presents an experimental evaluation of a morphing leading edge demonstrator by investigating its morphed shape, the level of induced strains in the airfoil skin, the actuation force, and the morphing mechanism’s capability to lock and transfer the applied loads. In addition, a finite element model of the demonstrator is assembled comprising an elastic morphing skin and a kinematic morphing mechanism. The obtained results are used to assess whether the demonstrator performs according to the design objectives, such as the target shape, the character of the morphing deformation and the morphing mechanism locking, applied during the design process. The comparison between experimental and numerical results yielded a good agreement in terms of observed morphed shape and pertaining strains. The average difference in morphed shape was less than 0.08% chord at the maximum actuator extension. The observed difference in the respective strains was less than 400 micro-strains. A significant difference, up to 70%, was observed in the actuation force, which was attributed to the modelling assumptions and to the force measurement technique employed in the experiment. Nevertheless, both results show good qualitative agreement showing similar trends.

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.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.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).Patients with higher 30-day mortality were those with a greater burden of comorbidities, with little education, and covered by Medicaid.

IntroductionHospital discharge data provide an important basis for determining priorities for injury prevention and monitoring trends in incidence. This study aims to illustrate the impact of a recent change in administrative practice on estimates of hospitalised injury incidence and to investigate the extent to which different case selection affects trends in injury incidence rates.MethodsNew Zealand (NZ) hospital discharges (2000–2014) with a primary diagnosis of injury were identified. Additional case selection criteria included first admissions only, and for serious injury, a high threat-to-life estimate. Comparisons were made, over time and by District Health Board, between hospitalised injury incidence estimates that included, or not, short-stay emergency department (SSED) discharges.ResultsOf the 1 229 772 injury hospital discharges, 365 114 were SSED; 16% of the annual total in 2000, 38% in 2014. Identification of readmissions prior to the exclusion of SSED discharges resulted in 30 724 cases being erroneously removed. Age-standardised rates of hospitalised injury over the 15-year period increased by, on average, 2.7% per year when SSED discharges were included; there was minimal secular change (−0.2%) when SSEDs were excluded. For serious hospitalised injury, the annual increase was 2.3% when SSED was included compared with 1.1% when SSEDs were excluded.ConclusionSpurious trends in hospitalised injury incidence can result when administrative practices are not appropriately accounted for. Exclusion of SSED discharges before the identification of readmissions and the use of a severity threshold are recommended to minimise the reporting bias in NZ hospitalised injury incidence estimates.

Introduction Aberrant function of granulosa cells has been implicated in the pathophysiology of PCOS. Materials & methods Granulosa lutein (GL) cells were collected during oocyte retrieval for IVF/ICSI. RT-qPCR was used to compare gene expression between 12 control women, 12 with ovulatory PCO and 12 with anovulatory PCOS. To examine which genes are directly regulated by androgens, GL cells from an additional 12 control women were treated in-vitro with 10 nM dihydrotestosterone (DHT). Results GL cells from women with PCOS showed reduced expression of CYP11A1 3-fold (p = 0.005), HSD17B1 1.8-fold (p = 0.02) and increased expression of SULT1E1 7-fold (p = 0.0003). Similar results were seen in ovulatory women with PCO. GL cells treated with 10 nM DHT showed a 4-fold (p = 0.03) increase in expression of SULT1E1 and a 5-fold reduction in SRD5A1 (p = 0.03). Conclusions These findings support the notion that aberrant regulation of steroid metabolism or action play a part in ovarian dysfunction in PCOS.

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.

To quantify head and neck cancer (HNC) mortality rates and identify racial and socioeconomic factors associated with 90-day mortality.The National Cancer Database (2004-2014) was queried for eligible HNC cases (n = 260,011) among adults treated with curative intent. Outcome of interest was any-cause 90-day mortality. Kaplan-Meier curves (Log-rank tests) estimated crude survival differences. A Cox proportional hazards model with further adjustments using the Šidák multiple comparison method adjusted for racial, socioeconomic and clinical factors.There were 9771 deaths (90-day mortality rate = 3.8%). There were crude differences in sex, race/ethnicity, comorbidity, distance, income, and insurance (Log-rank p-value 0.0001). In the final model, blacks (aHR = 1.10, 95% CI 1.00, 1.21) and males (aHR = 1.07; 95% CI 1.00, 1.15) had greater 90-day mortality hazard, as did those uninsured (aHR = 1.72; 95% CI 1.48, 1.99), covered by Medicaid (aHR = 1.72; 95% CI 1.53, 1.93) or Medicare (aHR = 1.40; 95% CI 1.27, 1.53). Residence in lower median income zip code was associated with greater 90-day mortality [(aHR$30,000 = 1.30; 95% CI 1.18, 1.44); (aHR $30,000-$34,999 = 1.24; 95% CI 1.13, 1.36); (aHR $35,000-$45,999 = 1.18; 95% CI 1.08, 1.27)]; and farther travel distance for treatment was associated with decreased 90-day mortality [(aHR 50-249.9 miles = 0.86; 95% CI 0.77, 0.97); (aHR 250 miles = 0.70; 95% CI 50, 0.99)].There are significant race and socioeconomic disparities among patients with HNC, and these disparities impact mortality within 90 days of treatment.

Introduction Anterior Cruciate Ligament(ACL) rupture is a common sporting injury. Return to sport is a key objective for patients. The aim of this study was to investigate return to pre-injury level sport at 12- and 24-months post reconstruction and to relate this to types of sport and to patient satisfaction. Method A questionnaire was developed, piloted, and then completed by 77 patients that had undergone ACL reconstruction between 2013-2016. Results 30% of patients returned to pre-injury level of sport at 12 months and 43% by 24 months’ post ACL reconstruction. There was a significant(P = 0.037) relationship between the type of sports that participants played prior to injury and the return to pre-injury level. Sports that involved jumping, hard pivoting and cutting were associated with a lower rate of return to sport. General health profile of the patients was found to be significantly higher in patients that returned to sport(P = 0.024). There was a significant association with return to sport and higher satisfaction and healthcare experience score(P = 0.001). Conclusions Patient satisfaction correlated with return to sport. This was inversely related to sports involving jumping, hard pivoting and cutting. Which further illustrates how patient satisfaction post ACL reconstruction was linked to type of sport.

As the United States faces unparalleled challenges due to COVID‐19, racial disparities in health and healthcare have once again taken center stage. If effective interventions to address racial disparities in transplantation, including those magnified by COVID‐19, are to be designed and implemented at the national level, it is first critical to understand the complex mechanisms by which structural, institutional, interpersonal, and internalized racism influence the presence of racial disparities in healthcare and transplantation. Specifically, we must deeply re‐evaluate how scientists and clinicians think about race in the transplant context, and we must actively shift our efforts from merely observing disparities to acknowledging and acting on racism as a root cause underlying the vast majority of these disparities. We must do better to ensure equitable access and outcomes for all transplant patients, including within the current COVID‐19 pandemic. We respectfully offer this viewpoint as a call to action to every reader to join us in working together to help dismantle racist influences and advance transplant equity.

Biofilms are complex microbial communities that present serious contamination risks to our environment and health. In this study, atmospheric air plasma and airborne acoustic ultrasound technology were applied to inactivate Escherichia coli and Listeria innocua biofilms. Both technologies were efficient in controlling, or completely inactivating, the target bacterial biofilms. Viability and metabolic assays, along with microscopy analysis, revealed that atmospheric air plasma and airborne acoustic ultrasound damaged both the bacterial biofilm cells and its structural integrity. Scanning electron microscopy images highlighted the disruption of the biofilms and pore formation in bacterial cells exposed to both the plasma and acoustic treatments. Elevated reactive oxygen and nitrogen species in bacterial cells treated with atmospheric air plasma, demonstrated their primary role in the observed bacterial inactivation process. Our findings provide potential antimicrobial strategies to combat bacterial biofilms in the food and healthcare sectors.

α1-Adrenergic receptors (ARs) are catecholamine-activated G protein-coupled receptors (GPCRs) that are expressed in mouse and human myocardium and vasculature, and play essential roles in the regulation of cardiovascular physiology. Though α1-ARs are less abundant in the heart than β1-ARs, activation of cardiac α1-ARs results in important biologic processes such as hypertrophy, positive inotropy, ischemic preconditioning, and protection from cell death. Data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) indicate that nonselectively blocking α1-ARs is associated with a twofold increase in adverse cardiac events, including heart failure and angina, suggesting that α1-AR activation might also be cardioprotective in humans. Mounting evidence implicates the α1A-AR subtype in these adaptive effects, including prevention and reversal of heart failure in animal models by α1A agonists. In this review, we summarize recent advances in our understanding of cardiac α1A-ARs.

BACKGROUND AND AIMS Estimates of racial disparity in cirrhosis have been limited by lack of large-scale, longitudinal data, which track patients from diagnosis to death and/or transplant. APPROACH AND RESULTS We analyzed a large, metropolitan, population-based electronic health record data set from seven large health systems linked to the state death registry and the national transplant database. Multivariate competing risk analyses, adjusted for sex, age, insurance status, Elixhauser score, etiology of cirrhosis, HCC, portal hypertensive complication, and Model for End-Stage Liver Disease-Sodium (MELD-Na), examined the relationship between race, transplant, and cause of death as defined by blinded death certificate review. During the study period, 11,277 patients met inclusion criteria, of whom 2,498 (22.2%) identified as Black. Compared to White patients, Black patients had similar age, sex, MELD-Na, and proportion of alcohol-associated liver disease, but higher comorbidity burden, lower rates of private insurance, and lower rates of portal hypertensive complications. Compared to White patients, Black patients had the highest rate all-cause mortality and non-liver-related death and were less likely to be listed or transplanted (P

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.

Right ventricular (RV) failure (RVF) is a serious disease with no effective treatment available. We recently reported a disease prevention study showing that chronic stimulation of α1A-adrenergic receptors (α1A-ARs), started at the time of RV injury, prevented the development of RVF. The present study used a clinically relevant disease reversal design to test if chronic α1A-AR stimulation, started after RVF was established, could reverse RVF. RVF was induced surgically by pulmonary artery constriction in mice. Two weeks after pulmonary artery constriction, in vivo RV fractional shortening as assessed by MRI was reduced by half relative to sham-operated controls (25 ± 2%, n = 27, vs. 52 ± 2%, n = 13, P < 10−11). Subsequent chronic treatment with the α1A-AR agonist A61603 for a further 2 wk resulted in a substantial recovery of RV fractional shortening (to 41 ± 2%, n = 17, P < 10−7 by a paired t-test) along with recovery of voluntary exercise capacity. Mechanistically, chronic A61603 treatment resulted in increased activation of the prosurvival kinase ERK, increased abundance of the antiapoptosis factor Bcl-2, and decreased myocyte necrosis evidenced by a decreased serum level of cardiac troponin. Moreover, A61603 treatment caused increased abundance of the antioxidant glutathione peroxidase-1, decreased level of reactive oxygen species, and decreased oxidative modification (carbonylation) of myofilament proteins. Consistent with these effects, A61603 treatment resulted in increased force development by cardiac myofilaments, which might have contributed to increased RV function. These findings suggest that the α1A-AR is a therapeutic target to reverse established RVF. NEW & NOTEWORTHY Currently, there are no effective therapies for right ventricular (RV) failure (RVF). This project evaluated a novel therapy for RVF. In a mouse model of RVF, chronic stimulation of α1A-adrenergic receptors with the agonist A61603 resulted in recovery of in vivo RV function, improved exercise capacity, reduced oxidative stress-related carbonylation of contractile proteins, and increased myofilament force generation. These results suggest that the α1A-adrenergic receptor is a therapeutic target to treat RVF.

Bacterial biofilms are difficult to inactivate due to their high antimicrobial resistance. Therefore, new approaches are required for more effective bacterial biofilm inactivation. Airborne acoustic ultrasound improves bactericidal or bacteriostatic activity which is safe and environmentally friendly. While, plasma activated water (PAW) is attracting increasing attention due to its strong antimicrobial properties. This study determined efficacy of combined airborne acoustic ultrasound and plasma activated water from both cold and thermal plasma systems in inactivating Escherichia coli K12 biofilms. The application of airborne acoustic ultrasound (15 min) alone was significantly more effective in reducing E. coli counts in 48 and 72 h biofilms compared to 30 min treatment with PAW. The effect of airborne acoustic ultrasound was more pronounced when used in combination with PAW. Airborne acoustic ultrasound treatment for 15 min of the E. coli biofilm followed by treatment with PAW significantly reduced the bacterial count by 2.2—2.62 Log10 CFU/mL when compared to control biofilm treated with distilled water. This study demonstrates that the synergistic effects of airborne acoustic ultrasound and PAW for enhanced antimicrobial effects. These technologies have the potential to prevent and control biofilm formation in food and bio-medical applications.

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.

Objective To determine if there are differences in mortality from oral cavity squamous cell carcinoma (OCSCC) based on oral cavity (OC) subsites. Methods Using the Surveillance, Epidemiology, and End Results Program (SEER) 9 database, patients with sequence number 0 or 1 squamous cell OCSCC were analyzed by OC subsite for 5-year cause-specific mortality (CSM) from OCSCC. Proportional hazards regression determined the association between 5-year CSM and OC subsites while controlling for treatment modality, stage, and demographic characteristics using hazard ratios. Significance was set at alpha = 0.05. Results 20,647 OC patients were included in the regression analysis. The most commonly diagnosed sites were floor of mouth (34.4%) and oral tongue (34.3%). Floor of mouth, upper gum, and retromolar trigone were associated with lower CSM compared to oral tongue. Not receiving surgery and receiving radiation were associated with increased CSM, and CSM increased with cancer staging when distant or regional disease was compared to localized disease. Also, patients diagnosed at 60 years or older and black patients had increased CSM. Conclusion Among OCSCC patients, those with oral tongue cancer are more likely to experience CSM than patients with floor of mouth, upper gum, and retromolar trigone cancer. It is important to understand these mortality related differences in the management of OCSCC patients. Understanding subsite-specific mortality may benefit prognosis counseling of OCSCC patients and elicit subsite-directed research as a means to improve outcomes. Level of evidence NA Laryngoscope, 129:1400-1406, 2019.

Background Cancer survivors face psychosocial issues that increase their risk of suicide. This study examined the risk of suicide across cancer sites, with a focus on survivors of head and neck cancer (HNC). Methods The Surveillance, Epidemiology, and End Results 18-registry database (from 2000 to 2014) was queried for the top 20 cancer sites in the database, including HNC. The outcome of interest was suicide as a cause of death. The mortality rate from suicide was estimated for HNC sites and was compared with rates for 19 other cancer sites that were included in the study. Poisson regression was used to estimate adjusted rate ratios (aRRs) and 95% confidence intervals (CIs) for 1) HNC versus non-HNC sites (the other 19 cancer sites combined), and 2) HNC versus each individual cancer site. Models were stratified by sex, controlling for race, marital status, age, year, and stage at diagnosis. Results There were 404 suicides among 151,167 HNC survivors from 2000 to 2014, yielding a suicide rate of 63.4 suicides per 100,000 person-years. In this timeframe, there were 4493 suicides observed among 4219,097 cancer survivors in the study sample, yielding an incidence rate of 23.6 suicides per 100,000 person-years. Compared with survivors of other cancers, survivors of HNC were almost 2 times more likely to die from suicide (aRR, 1.97; 95% CI, 1.77-2.19). There was a 27% increase in the risk of suicide among HNC survivors during the period from 2010 to 2014 (aRR, 1.27; 95% CI, 1.16-1.38) compared with the period from 2000 to 2004. Conclusions Although survival rates in cancer have improved because of improved treatments, the risk of death by suicide remains a problem for cancer survivors, particularly those with HNC.

OBJECTIVE The literature on nasopharyngeal carcinoma survival in the United States has focused mostly on Whites or Asians and not much is known about survivorship in other minority racial and ethnic groups. We aimed to determine the disease-specific survival rate and prognostic factors for nasopharyngeal carcinoma survival across the minority United States population. DESIGN A retrospective cohort study. SETTING The Surveillance, Epidemiology and End Results (SEER) 13 database from 1992 to 2014 was queried for adult cases of nasopharyngeal carcinoma (n = 2549). PARTICIPANTS Eligible cases were Blacks, Hispanics, Asians/Pacific Islanders, American Indians/Alaska Natives; White patients were excluded. MAIN OUTCOMES MEASURE A multivariable competing risk survival analysis yielded hazard ratios (HR) for competing mortality and was used to identify independent prognostic factors for survival. RESULTS Non-Hispanic American Indians/Alaska Natives consistently had the worst cause-specific survival of any group and that non-Hispanic Asians/Pacific Islanders consistently had the best survival (P < 0.001). Even after adjusting for other poor prognostic factors in the study, including older age, keratinising histology, and lack of radiation treatment, non-Hispanic American Indians/Alaska Natives had more than double hazards of death from nasopharyngeal cancer compared with non-Hispanic Asians/Pacific Islanders (aHR = 2.63, 95% CI 1.67, 4.13). CONCLUSIONS There are disparities in nasopharyngeal carcinoma survival among racial and ethnic minority groups in the United States, with American Indians/Alaskan Natives faring worst. It is critical that future research focuses on nasopharyngeal carcinoma among this population to improve survivorship and mitigate cancer-related health disparities.

Objectives/hypothesis Head and neck squamous cell carcinoma (HNSCC) prognosis strongly correlates with demographic factors. This study aimed to determine whether demographic predictors of HNSCC survival differ between age cohorts, with an emphasis on the growing elderly demographic. Study design Outcomes research. Methods Adults with squamous cell carcinoma of the upper aerodigestive tract were identified from the Surveillance, Epidemiology and End Results 18 database. Demographic and oncologic factors were compared between three age groups: 18 to 49, 50 to 74, and >75 years. Factors associated with cancer-specific survival were assessed in each cohort using subdistribution hazard ratio (sHR) and 95% confidence interval (CI) produced by multivariate competing risk models. Results A cohort of 69,098 patients included 10,588 (15.3%) 75 years or older and 9,882 (14.3%) less than 50 years old. Older patients were more often female (35.4% vs. 25.1% aged 18-49 years and 20.4% aged 50-74 years), white (78.7% vs. 69.4% and 75.9%), insured (63.5% vs. 46.5% and 56.8%), and married (56.6% vs. 53% and 51.1%), but received adequate treatment less often (72.0% vs. 86.3% and 82.7%). In the older cohort, male sex was associated with lower mortality (sHR: 0.92, 95% CI: 0.85-1.00), and unlike the younger cohorts, black race was no longer associated with mortality (sHR: 1.07, 95% CI: 0.94-1.22). Marriage was associated with lower mortality in all age groups but with diminishing effects (single sHR: young 1.52, middle 1.31, older 1.14). Conclusions Elderly HNSCC patients have distinct effects from demographic prognostic factors and should be considered a separate subgroup with unique epidemiology, risks, and preferences. Level of evidence 2c Laryngoscope, , 129:146-153, 2018.

Aim. To describe the top five causes of preventable health conditions among Pacific children (Cook Island, Fijian, Niuean, Samoan, Tongan, Tokelauan) aged 0-4 years living in New Zealand (NZ), and to make comparisons of these rates with NZ’s population who were of neither Maori nor Pacific ethnicity (NMNP). Method. This study is a retrospective analysis of preschool Ambulatory Sensitive Hospitalisations (ASH) by ethnicity. The data, from 2010 to 2014, was extracted from The National Minimum Dataset. Results. The top five preventable health conditions among Pacific under 5’s were asthma and wheeze, gastroenteritis, dental, skin infections and pneumonia. Rates for all Pacific children with any of the ASH conditions were four to five times higher among Pacific, than among NMNP, from 2000 to 2014. Pacific children were also significantly more likely to present with bronchiectasis and rheumatic fever or rheumatic heart disease (RR 25.7 and 26.4 respectively). Conclusion. Pacific children aged 0-4 years are more likely to be exposed to health conditions that are considered preventable . The most common preventable health conditions experienced by Pacific children were asthma and wheeze, gastroenteritis, dental, skin infections and pneumonia. These findings highlight the importance of investing in effective prevention strategies to further investigate and address the underlying causes of these conditions.

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 byInternational Statistical Classification of Diseases and Related Health Problems, Tenth Revisioncodes (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.

Background Sleep Disordered Breathing (SDB) in children is characterised by snoring and breathing difficulties during sleep. Small clinical trials suggest intranasal corticosteroids reduce SDB severity as defined by polysomnography. We assessed the efficacy of intranasal corticosteroid for improving symptoms and quality of life (QOL) in children with SDB. Methods This is a double-blind, randomised, placebo-controlled trial of healthy children 3-12y referred to a specialist with SDB symptoms. Exclusions were previous adenotonsillectomy, obesity or severe SDB. Participants received daily intranasal mometasone furoate 50micrograms or normal saline for 6 weeks. The primary outcome was resolution of symptoms measured by SDB score. Secondary outcomes were SDB symptom scores, QOL, behaviour, parent and surgeon perceived need for surgery, and parent satisfaction with treatment. Results 276 participants were recruited; 138 in each group. 127 and 123 participants had primary outcome data at 6 weeks in the mometasone and saline groups respectively. Baseline age, atopic history, symptom severity and QOL were similar between groups. Resolution of SDB symptoms occurred in 44% [95%CI 35–53] of the mometasone group and 40% [95%CI 32–49] of the saline group; risk difference 4% [95%CI -0.8–16] p=0.511. Secondary outcomes were not different between groups. Discussion This large RCT, using clinical rather than polysomnographic outcomes to investigate the efficacy of mometasone on symptoms of SDB, found substantial rates of symptom resolution after 6 weeks in both groups. However, we found no difference in treatment effect between 6 weeks of intranasal mometasone over saline, for management of SDB symptoms in childhood.

Failure of the right ventricle (RV) is a serious disease with a poor prognosis and limited treatment options. Signaling by α1-adrenergic receptors (α1-ARs), in particular the α1A-subtype, mediate cardioprotective effects in multiple heart failure models. Recent studies have shown that chronic treatment with the α1A-subtype agonist A61603 improves function and survival in a model of left ventricular failure. The goal of the present study was to determine if chronic A61603 treatment is beneficial in a RV failure model. We used tracheal instillation of the fibrogenic antibiotic bleomycin in mice to induce pulmonary fibrosis, pulmonary hypertension, and RV failure within 2 wk. Some mice were chronically treated with a low dose of A61603 (10 ng·kg−1·day−1). In the bleomycin model of RV failure, chronic A61603 treatment was associated with improved RV fractional shortening and greater in vitro force development by RV muscle preparations. Cell injury markers were reduced with A61603 treatment (serum cardiac troponin I, RV fibrosis, and expression of matrix metalloproteinase-2). RV oxidative stress was reduced (using the probes dihydroethidium and 4-hydroxynonenal). Consistent with lowered RV oxidative stress, A61603 was associated with an increased level of the cellular antioxidant superoxide dismutase 1 and a lower level of the prooxidant NAD(P)H oxidase isoform NOX4. In summary, in the bleomycin model of RV failure, chronic A61603 treatment reduced RV oxidative stress, RV myocyte necrosis, and RV fibrosis and increased both RV function and in vitro force development. These findings suggest that in the context of pulmonary fibrosis, the α1A-subtype is a potential therapeutic target to treat the failing RV. NEW & NOTEWORTHY Right ventricular (RV) failure is a serious disease with a poor prognosis and no effective treatments. In the mouse bleomycin model of RV failure, we tested the efficacy of a treatment using the α1A-adrenergic receptor subtype agonist A61603. Chronic A61603 treatment improved RV contraction and reduced multiple indexes of RV injury, suggesting that the α1A-subtype is a therapeutic target to treat RV failure.

Scanning Wizard software helps scanning users improve the setup of their switch and scanning system. This study evaluated Scanning Wizard's effectiveness and usability. Ten people who use switch scanning and ten practitioners used Scanning Wizard in the initial session. Usability was high, based on survey responses averaging over 4.5 out of 5, and qualitative feedback was very positive. Five switch users were able to complete the multi-week protocol, using settings on their own scanning system that were recommended from the Scanning Wizard session. Using these revised settings, text entry rates improved by an average of 71%, ranging from 29% to 172% improvement. Results suggest that Scanning Wizard is a useful tool for improving the configuration of scanning systems for people who use switch scanning to communicate. Implications for Rehabilitation Some individuals with severe physical impairments use switch scanning for spoken and written communication. Scanning Wizard software helps scanning users improve the setup of their switch and scanning system. This study demonstrated high usability of Scanning Wizard (with 10 switch userpractitioner teams) and increased text entry rate by an average of 71% (for five switch users). Results suggest that Scanning Wizard is a useful tool for improving the configuration of scanning systems for people who use switch scanning to communicate.

To determine differences in oropharyngeal squamous cell carcinoma (OPSCC) incidence between 1975 and 2014 stratified by race, sex, and age.We obtained age-adjusted OPSCC incidence rates for race and sex groups from 1975 to 2014 using the Surveillance, Epidemiology, and End Results 9 database. We defined OPSCC as cancers of the base of tongue, lingual/palatine tonsil, oropharynx, soft palate, uvula, and Waldeyer's ring. We used Joinpoint analyses to determine incidence trends for race/sex/age groupings.There were 38,624 oropharyngeal primary tumors in the analyses. Males accounted for 74% of sample population, and whites accounted for 84% of tumors. Overall, there was a 57.3% increase in incidence of oropharyngeal between 1975 and 2014. For blacks and whites, average incidence was lower for females than males. Rates for black males aged ≥50years was highest for most of the follow-up time but decreased sharply around 1988 and were surpassed by the significant increase in incidence in white males aged 50-59 (1995-2014 APC=4.07, p0.001) and ≥60years (2002-2014 APC=4.25, p0.001). For males aged ≥60, whites had higher rates than blacks starting in 2010. OPSCC incidence in White males (10.99 per 100,000 person-years) surpassed rates in Blacks (10.14 per 100,000 person-years) beginning in 2008.OPSCC has significantly increased in the United States in the last 40 years. This overall increase in OPSCC can primarily be attributed to white males. OPSCC prevention and early detection efforts could target these demographic factors to decrease rising OPSCC incidence.

IntroductionUncontrolled haemorrhage is the leading cause of death on the battlefield, and two-thirds of these deaths result from non-compressible haemorrhage. Blood salvage and autotransfusion represent an alternative to conventional blood transfusion techniques for austere environments, potentially providing blood to the casualty at point of injury. The aim of this paper is to describe the design, development and initial proof-of-concept testing of a portable blood salvage and autotransfusion technology to enhance survivability of personnel requiring major medical interventions in austere or military environments.MethodA manually operable, dual-headed pump was developed that removes blood from site of injury to a collection reservoir (upper pump) and back to casualty (lower pump). Theoretical flow rate calculations determined pump configuration and a three-dimensionally printed peristaltic pump was manufactured. Flow rates were tested with fresh bovine blood under laboratory conditions representative of the predicted clinical environment.ResultsMathematical modelling suggested flow rates of 3.6 L/min and 0.57 L/min for upper and lower pumps. Using fresh bovine blood, flow rates produced were 2.67 L/min and 0.43 L/min. To mimic expected battlefield conditions, upper suction pump flow rate was calculated using a blood/air mixture.ConclusionThe authors believe that this technology can potentially enhance survivability for casualties in austere and deployed military settings through autotransfusion and cell concentration. It reduces negative effects of blood donation on the conventional donor pool, and potentially negates the logistical constraints associated with allogenic transfusions.

Summary: Alpha-1 adrenergic receptors (α1-ARs) play adaptive and protective roles in the heart. Dabuzalgron is an oral selective α1A-AR agonist that was well tolerated in multiple clinical trials of treatment for urinary incontinence, but has never been used to treat heart disease in humans or animal models. In this study, the authors administered dabuzalgron to mice treated with doxorubicin (DOX), a widely used chemotherapeutic agent with dose-limiting cardiotoxicity that can lead to heart failure (HF). Dabuzalgron protected against DOX-induced cardiotoxicity, likely by preserving mitochondrial function. These results suggest that activating cardiac α1A-ARs with dabuzalgron, a well-tolerated oral agent, might represent a novel approach to treating HF. Key Words: alpha adrenergic receptors, anthracyclines, cardioprotection, catecholamines, heart failure

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

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 3histologic 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.

Background Risk stratification following an acute coronary syndrome (ACS) is of utmost importance, in order to identify patients at higher risk of subsequent cardiovascular events. Diabetic patients have a significantly worse prognosis, so new risk prediction tools are important to better identify and risk stratify high risk patients within this important ACS subpopulation. Aim The aim of this study was to identify the best predictors of a new ACS, in a single-center database of ACS, resorting to machine learning and artificial intelligence, and to compare the Global Registry of Acute Coronary Events (GRACE) risk score's relevance for risk discrimination in a general ACS population versus a subpopulation of diabetic patients. Methods In a single center, 5977 patients admitted due to ACS between 2004 and 2017 and alive at discharge were studied. In the subpopulation of diabetic patients (n=3429), each covariate present in the database was analyzed separately with a Cox proportional hazard model with three terms – subpopulation belonging indicator, covariate, interaction term. The p-value of the interaction term was used to rank variables. The more significant the interaction term, the stronger the change in relationship between patients in the subpopulation and the risk of a new ACS, compared to the one in the general population. Results During long term follow-up, 13% of patients (n=771) experienced a second event. Kaplan-Meier curve represents how ACS free-survival depends on the GRACE risk score and group of interest. In the general population and in the subpopulation of diabetic patients, the GRACE score was used to further divide patients into 3 terciles, of which only the lower and upper tercile are shown (GRACE ≤113 and GRACE >144, respectively). The solid lines represent Kaplan-Meier curves for diabetic patients, and the dotted lines in the general population. Pink or grey colour of the curves represent the stratification level of the covariate. Conclusions In our model, the GRACE risk score was found to be a better discriminator of risk of futher ACS in diabetic patients than in the general ACS population. Strikingly, a higher GRACE score predicts a lower rate of readmission, probably because many patients will die in the index hospitalization or out of hospital. This finding reinforces the usefulness of the GRACE score in high risk patients and may improve risk stratisfication in diabetic post-ACS patients, making sure that they are closely followed and submitted to optimal risk factor management, in order to improve their post-ACS prognosis.

Three dogs who were presented with cutaneous lesions and had histopathologic findings consistent with pemphigus foliaceus were treated with injectable polysulfated glycosaminoglycan as an adjunctive to systemic immune-modulatory therapy. These patients were not adequately controlled with oral glucocorticoids in conjunction with cyclosporine, azathioprine, and/or mycophenolate. Polysulfated glycosaminoglycan contributed to induction of remission and reduced glucocorticoid doses in all dogs.

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.

Background The requirement for IL-23 in driving IL-17A and IL-17F production in humans is incompletely understood. Preclinical data support IL-17F, together with IL-17A, as a key driver of chronic tissue inflammation.1 MAIT cells, an innate-like T cell population, uniformly express RORγt but only a minority have been shown to produce IL-17A.2 Dysregulation in frequency and function of MAIT cells has been associated with IL-17A-mediated inflammatory diseases, including PsA and AS.3,4 IL-17F production in MAIT cells remains largely unexplored. Objectives To explore the importance of IL-23 signalling in MAIT cell-derived IL-17A and IL-17F production, examine the presence of MAIT cells in psoriatic lesional skin and assess the contribution of MAIT cell-derived IL-17A and IL-17F using in vitro models of skin inflammation. Methods IL-17A and IL-17F production by MAIT cells was assessed by flow cytometry, ELISA, qPCR and CyTOF upon activation by anti-CD3/CD28 or fixed E. coli via MR1–presented riboflavin metabolites, with or without disease-relevant recombinant cytokines or an IL-23-neutralising antibody. RNAscope was utilised to observe MAIT cells in psoriatic lesional skin. MAIT cell supernatant, generated from FACS sorted activated MAIT cells, was cultured with normal human dermal fibroblasts (NHDFs) in the presence of IL-17-isoform-specific antibodies, including bimekizumab, a monoclonal antibody that potently and selectively neutralises both IL-17A and IL-17F. Results Optimal MAIT cell IL-17A and IL-17F production occurred upon T cell receptor triggering with IL-12 and IL-18, independently of IL-23. IL-17F expression was greater at both gene and protein levels than IL-17A. The kinetics and threshold of activation for IL-17A and IL-17F suggest tighter regulation compared with other inflammatory cytokines, including IFNγ and TNF. Optimal MAIT cell IL-17A and IL-17F production requires monocytes, which contribute to IL-12 production upon IL-18 stimulation. MAIT cells were abundant in psoriatic lesional skin. NHDFs cultured with supernatant generated from activated MAIT cells produced inflammatory mediators IL-6, IL-8 and CCL2, which were reduced upon inhibition of either IL–17A or IL-17F, with optimal suppression achieved following dual neutralisation with bimekizumab. Conclusion IL-17A and IL-17F can be produced from MAIT cells independently of IL-23, and contribute to inflammatory responses in NHDFs. These results support dual neutralisation of IL-17A and IL-17F as a complete and targeted approach to supress IL–17–driven inflammatory responses. Reference [1] Glatt Ann Rheum Dis 2018;77:523–32, 2Dusseaux Blood 2011;117:1250–59, 3Menon Arthritis Rheumatol 2014;66:1272–81, 4Gracey Ann Rheum Dis 2016;75:2124–32 Acknowledgement Funded by UCB Pharma. The authors would like to acknowledge Alexandra Webster MSc, of iMed Comms, an Ashfield Company, for editorial support that was funded by UCB Pharma in accordance with Good Publication Practice (GPP3) guidelines. The authors acknowledge Alvaro Arjona, PhD, of UCB Pharma, for publication and editorial support. Disclosure of Interests Suzanne Cole Employee of: UCB Pharma, Catherine Simpson Employee of: UCB Pharma, Remi Okoye Shareholder of: UCB Pharma, Employee of: UCB Pharma, Meryn Griffiths Consultant for: UCB Pharma, Employee of: UCB Pharma, Dominique Baeten Shareholder of: UCB Pharma, Employee of: UCB Pharma, Stevan Shaw Employee of: UCB Pharma, Ash Maroof Shareholder of: UCB Pharma, Employee of: UCB Pharma