Activity of IL-12/15/18 primed natural killer cells against hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is common, but remains difficult to treat. Natural killer (NK) cells are cells of the innate immune system that have potent anti-cancer activity. Recent work has shown that stimulation with IL-12/15/18 leads to the generation of NK cells with enhanced functional and putative "memory" properties. We have investigated the activity of these NK cells against HCC cell lines in vitro and in a mouse model. METHODS: NK cells from healthy donors or individuals with HCC were activated with IL-12/15/18 in vitro and tested for cytotoxic activity against a panel of human HCC cell lines. IL-12/15/18 primed murine NK cells were then infused into a murine model of spontaneously arising HCC to test for anti-tumor activity. RESULTS: NK cells from patients and healthy controls had similar expression levels of activating and inhibitory NK cell receptors. However, proliferation of NK cells from HCC patients was weaker than healthy controls in response to IL-12/15/18 and IL-2 (p < 0.001 at day 9). In vitro, NK cells from both groups of individuals killed HCC targets to similar levels and this was unrelated to NKG2D expression. In a spontaneous model of HCC, IL-12/15/18 activated NK cells trafficked to the liver and resulted in lower levels of spontaneous HCC formation (p < 0.01). CONCLUSION: Cytokine-primed NK cells from patients with HCC have similar levels of activity against HCC cell lines as those from healthy controls. This type of activated NK cell has immunotherapeutic potential against hepatocellular carcinoma.

Hepatitis C bio-behavioural surveys in people who inject drugs-a systematic review of sensitivity to the theoretical assumptions of respondent driven sampling.

BACKGROUND: New, more effective and better-tolerated therapies for hepatitis C (HCV) have made the elimination of HCV a feasible objective. However, for this to be achieved, it is necessary to have a detailed understanding of HCV epidemiology in people who inject drugs (PWID). Respondent-driven sampling (RDS) can provide prevalence estimates in hidden populations such as PWID. The aims of this systematic review are to identify published studies that use RDS in PWID to measure the prevalence of HCV, and compare each study against the STROBE-RDS checklist to assess their sensitivity to the theoretical assumptions underlying RDS. METHOD: Searches were undertaken in accordance with PRISMA systematic review guidelines. Included studies were English language publications in peer-reviewed journals, which reported the use of RDS to recruit PWID to an HCV bio-behavioural survey. Data was extracted under three headings: (1) survey overview, (2) survey outcomes, and (3) reporting against selected STROBE-RDS criteria. RESULTS: Thirty-one studies met the inclusion criteria. They varied in scale (range 1-15 survey sites) and the sample sizes achieved (range 81-1000 per survey site) but were consistent in describing the use of standard RDS methods including: seeds, coupons and recruitment incentives. Twenty-seven studies (87%) either calculated or reported the intention to calculate population prevalence estimates for HCV and two used RDS data to calculate the total population size of PWID. Detailed operational and analytical procedures and reporting against selected criteria from the STROBE-RDS checklist varied between studies. There were widespread indications that sampling did not meet the assumptions underlying RDS, which led to two studies being unable to report an estimated HCV population prevalence in at least one survey location. CONCLUSION: RDS can be used to estimate a population prevalence of HCV in PWID and estimate the PWID population size. Accordingly, as a single instrument, it is a useful tool for guiding HCV elimination. However, future studies should report the operational conduct of each survey in accordance with the STROBE-RDS checklist to indicate sensitivity to the theoretical assumptions underlying the method. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015019245.

What do tomorrow's doctors need to learn about ecosystems? - A BEME Systematic Review: BEME Guide No. 36.

BACKGROUND: Human health is fundamentally determined by the health of ecosystems. Guidance is lacking about how to address the topic of ecosystems within medical education. AIMS: To determine the nature of discussions around ecosystems in the educational, medical and medical education literature. To identify learning needs of tomorrow's doctors. METHODS: A narrative synthesis approach was used. Systematic searches were completed in 14 databases. Two independent reviewers screened results. Preliminary synthesis included textual descriptions and quality appraisal. Data were analysed using the Education for Sustainable Healthcare framework and thematic analysis. Relationships between studies were explored. Best evidence synthesis, contacting authors of primary studies and critical reflection reinforced robustness. RESULTS: Six thousand seven hundred and fifty-three abstracts and 123 full texts were screened. Twenty-seven studies were included. Many studies lacked clear reporting. Medical students and doctors displayed knowledge about ecosystems, but lacked confidence to enact sustainable practices. Education about causes and consequences of environmental change is required. Few studies proposed specific learning objectives. CONCLUSIONS: To prepare for roles as health care workers and leaders, medical students must learn about relationships between ecosystems, health and health care. The Education for Sustainable Healthcare framework outlines essential knowledge and attitudes but requires addition of practical competencies. Further research should explore the framework's relevance in different contexts, in order to structure training accordingly.