Treating laryngopharyngeal reflux: Evaluation of an anti-reflux program with comparison to medications

Objective

To determine if an anti-reflux induction program relieves laryngopharyngeal reflux (LPR) symptoms more effectively than medication and behavioral changes alone.

Targeted Therapies in the Treatment of Sarcomas

About 50% of sarcomas have specific pathology-defining molecular alterations including mutations, fusion genes, and gene amplifications. Some of these alterations appear to be oncogenic drivers, and a subset can be utilized as targets for standard or experimental molecularly targeted agents in the clinic. In addition, immunotherapies may have a growing role in the treatment of sarcomas in the future.     

IL-8 correlates with nonresponse to neoadjuvant nivolumab in HPV positive HNSCC via a potential extracellular vesicle miR-146a mediated mechanism

Therapy using anti-PD-1 immune checkpoint inhibitors (ICI) has revolutionized the treatment of many cancers including head and neck squamous cell carcinomas (HNSCC), but only a fraction of patients respond. To better understand the molecular mechanisms driving resistance, we performed extensive analysis of plasma and tumor tissues before and after a 4-week neoadjuvant trial in which HNSCC patients were treated with the anti-PD-1 inhibitor, nivolumab. Luminex cytokine analysis of patient plasma demonstrated that HPV^pos nonresponders displayed high levels of the proinflammatory chemokine, interleukin-8 (IL-8), which decreased after ICI treatment, but remained higher than responders. miRNAseq analysis of tetraspanin-enriched small extracellular vesicles (sEV) purified from plasma of HPV^pos nonresponders demonstrated significantly lower levels of seven miRNAs that target IL-8 including miR-146a. Levels of the pro-survival oncoprotein Dsg2, which has been to down-regulate miR-146a, are elevated with HPV^pos tumors displaying higher levels than HPV^neg tumors. Dsg2 levels decrease significantly following ICI in responders but not in nonresponders. In cultured HPV^pos cells, restoration of miR-146a by forced expression or treatment with miR-146a-loaded sEV, reduced IL-8 level, blocked cell cycle progression, and promoted cell death. These findings identify Dsg2, miR-146a, and IL-8 as potential biomarkers for ICI response and suggest that the Dsg2/miR-146a/IL-8 signaling axis negatively impacts ICI treatment outcomes and could be targeted to improve ICI responsiveness in HPV^pos HNSCC patients.     

A conduit between epidemiological research and regional health policy

Objective : To transform data from a research setting into a format that could be used to support strategies encouraging healthy lifestyle choices and service planning within local government. Methods : Details of the health status and lifestyle behaviours of the Geelong, Victoria, population were generated independently by the Geelong Osteoporosis Study (GOS), a prospective population‐based cohort study. Recent GOS follow‐up phases provided evidence about patterns of unhealthy diet, physical inactivity, smoking and harmful alcohol use. These factors are well‐recognised modifiable risk factors for chronic disease; the dataset was complemented with prevalence estimates for musculoskeletal disease, obesity, diabetes, cardiovascular disease, asthma and cancer. Results : Data were provided to Healthy Together Geelong in aggregate form according to age, sex and suburb. A population statistics company used the data to project health outcomes by suburb for use by local council. This data exchange served as a conduit between epidemiological research and policy development. Conclusion and implications : Regional policy makers were informed by local evidence, rather than national or state health survey, thereby optimising potential intervention strategies.