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Necroptosis molecular elements: The latest conclusions with regards to fresh necroptosis authorities.
Authors, editors and peer-reviewers should make an effort to improve completeness and adequacy of Cochrane RoB assessment in non-Cochrane reviews. OBJECTIVES Classical meta-analyses routinely treated studies with no events in both arms non-informative and excluded them from analyses. This study assessed whether such studies contain information and have influence on the conclusions of meta-analyses. DESIGN and setting We collected meta-analyses of binary outcomes with at least one study having no events in both arms from Cochrane systematic reviews (2003-2018). We used the generalized linear mixed model to reanalyze these meta-analyses by two approaches one including studies with no events in both arms and one excluding such studies. The magnitude and direction of odds ratio (OR), p-value, and width of 95% confidence interval (CI) were compared. A simulation study was conducted to examine the robustness of results. RESULTS We identified 442 meta-analyses. In comparing paired meta-analyses that included studies with no events in both arms versus those not, 8 (1.80%) resulted in different directions on OR; 41 (9.28%) altered conclusions on statistical significance. Substantial changes occurred on p-value (55.66% increased, 44.12% decreased) and the width of 95% CI (50.68% inflated, 49.32% declined) when excluding studies with no events. Simulation study confirmed these findings CONCLUSIONS Studies with no events in both arms are not necessarily non-informative. Excluding such studies may alter conclusions. OBJECTIVES To examine the design, conduct, and analysis of systematic reviews assessing drug safety through a cross-sectional survey. STUDY DESIGN AND SETTING We searched PubMed to identity systematic reviews published in the Cochrane Database of Systematic Reviews and Core Clinical Journals indexed in 2015, and randomly sampled systematic reviews assessing drug effects at a 11 ratio of Cochrane and non-Cochrane reviews. Teams of two investigators independently conducted study screening and collected data, using pre-specified, standardized questionnaires. In addition to general information, we collected details about the planning and analyses of safety outcomes. RESULTS We included 120 systematic reviews, including 60 Cochrane and 60 non-Cochrane ones. Most reviews searched PubMed/MEDLINE (n=117, 97.5%), EMBASE (n=105, 87.5%) and Cochrane CENTRAL (n=110, 91.7%), and conducted independent and duplicate study selection (n=98, 81.7%), risk of bias assessment (n=105, 87.5%), and data collection (n=105, 87.5%). On the overall quality of evidence with the GRADE approach. BACKGROUND & AIMS The benefits of prophylactic clipping to prevent bleeding after polypectomy are unclear. We conducted an updated meta-analysis of randomized trials to assess the efficacy of clipping in preventing bleeding after polypectomy, overall and according to polyp size and location. METHODS We searched the Medline/PubMed, EMBASE, and Scopus databases randomized trials that compared effects of clipping vs not clipping to prevent bleeding after polypectomy. We performed a random-effects meta-analysis to generate pooled relative risks (RRs) with 95% CIs. Multilevel random-effects meta-regression analysis was used to combine data on bleeding after polypectomy and estimate associations between rates of bleeding and polyp characteristics. RESULTS We analyzed data from 9 trials, comprising 7197 colorectal lesions (22.5% 20 mm or larger, 49.2% with proximal location). Clipping, compared with no clipping, did not significantly reduce the overall risk of post-polypectomy bleeding (2.2% with clipping vs 3.3% with no clipping; RR, 0.69; 95% CI, 0.45-1.08; P=.072). Clipping significantly reduced risk of bleeding after removal of polyps that were 20 mm or larger (4.3% had bleeding after clipping vs 7.6% had bleeding with no clipping; RR, 0.51; 95% CI, 0.33-0.78; P=.020) or that were in a proximal location (3.0% had bleeding after clipping vs 6.2% had bleeding with no clipping; RR, 0.53; 95% CI, 0.35-0.81; P less then .001). In multilevel meta-regression analysis that adjusted for polyp size and location, prophylactic clipping was significantly associated with reduced risk of bleeding after removal of large proximal polyps (RR, 0.37; 95% CI, 0.22-0.61; P=.021) but not small proximal lesions (RR, 0.88; 95% CI, 0.48-1.62; P=0.581). CONCLUSIONS In a meta-analysis of randomized trials, we found that routine use of prophylactic clipping does not reduce risk of post-polypectomy bleeding, overall. However, clipping appeared to reduce bleeding after removal of large (more than 20 mm), proximal lesions. BACKGROUND & AIMS Intestinal microfold (M) cells are a unique subset of intestinal epithelial cells in the Peyer's patches that regulate mucosal immunity, serving as portals for sampling and uptake of luminal antigens. The inability to efficiently develop human M cells in cell culture has impeded studies of the intestinal immune system. We aimed to identify signaling pathways required for differentiation of human M cells and establish a robust culture system using human ileum enteroids. METHODS We analyzed transcriptome data from mouse Peyer's Patches to identify cell populations in close proximity to M cells. We used the human enteroid system to determine which cytokines were required to induce M cell differentiation. We performed transcriptome, immunofluorescence, scanning electron microscope, and transcytosis experiments to validate the development of phenotypic and functional human M cells. RESULTS A combination of retinoic acid and lymphotoxin induced differentiation of glycoprotein 2-positive human M cells, which lack apical microvilli structure. Upregulated expression of innate immune-related genes within M cells correlated with a lack of viral antigens after rotavirus infection. Human M cells, developed in the enteroid system, internalized and transported enteric viruses, such as rotavirus and reovirus, across the intestinal epithelium barrier in the enteroids. CONCLUSIONS We identified signaling pathways required for differentiation of intestinal M cells, and used this information to create a robust culture method to develop human M cells with capacity for internalization and transport of viruses. Studies of this model might increase our understanding of antigen presentation and the systemic entry of enteric pathogens in the human intestine. selleck
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