The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
BACKGROUND In 2006, it was estimated that 47 million people in the United States are without insurance. Studies have shown that patients who are uninsured or are insured by Medicaid are more likely to present with more advanced cancer. The objective of this study was to examine whether cancer recurrence and mortality of patients diagnosed with squamous cell carcinoma of the head and neck are associated with insurance status, after adjusting for known cancer risk factors. The main outcome measures were overall survival and relapse-free survival. METHODS Retrospective cohort of patients with a biopsy-proven primary squamous cell carcinoma of the oral cavity, pharynx, or larynx diagnosed or treated at the University of Pittsburgh Medical Center between 1998 and 2007. Patients were stratified by their insurance status, including private insurance, uninsured/Medicaid, Medicare disability (Medicare under age 65), and Medicare 65 years +. Covariates included age, gender, race, smoking status, alcohol consumption, anatomic tumor site, treatment, stage at diagnosis, and occupational prestige score. Cox proportional hazards regression was used to estimate the effect of insurance status on overall survival, relapse-free survival, tumor stage, and lymph node involvement. RESULTS A total of 1231 patients were included in the analysis. Patients with Medicaid/uninsured (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.07-2.11) and Medicare disability (HR, 1.69; 95% CI, 1.16-2.48) had significantly lower overall survival compared with patients with private insurance; the result was independent of variables known to affect outcome, such as alcohol and tobacco use. For all squamous cell carcinoma of the head and neck (SCCHN) cancer sites, Medicaid and uninsured patients were significantly more likely to present with an advanced stage tumor at diagnosis (odds ratio [OR] = 2.94; 95% CI, 1.72-5.01) and to present with at least 1 positive lymph node (OR = 1.84; 95% CI, 1.16-2.90) compared with patients with private insurance. CONCLUSIONS Patients with Medicaid/uninsured and Medicare disability were at increased risk of death after a diagnosis of SCCHN when compared with patients with private insurance, after adjustment for age, gender, race, smoking, alcohol use, site, socioeconomic status, treatment, and cancer stage.
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