Helicobacter pylori and microRNAs:Relation with innate immunity and progression of preneoplastic conditions

The accepted paradigm for intestinal-type gastric cancer pathogenesis is a multistep progression from chronic gastritis induced by Helicobacter pylori(H. pylori) to gastric atrophy, intestinal metaplasia, dysplasia and ultimately gastric cancer. The genetic and molecular mechanisms underlying disease progression are still not completely understood as only a fraction of colonized individuals ever develop neoplasia suggesting that bacterial, host and environmental factors are involved. Micro RNAs are noncoding RNAs that may influence H. pylori-related pathology through the regulation of the transcription and expression of various genes, playing an important role in inflammation, cell proliferation, apoptosis and differentiation. Indeed, H. pylori have been shown to modify micro RNA expression in the gastric mucosa and micro RNAs are involved in the immune host response to the bacteria and in the regulation of the inflammatory response. Micro RNAs have a key role in the regulation of inflammatory pathways and H. pylori may influence inflammation-mediated gastric carcinogenesis possibly through DNA methylation and epigenetic silencing of tumor suppressor micro RNAs. Furthermore, micro RNAs influenced by H. pylori also have been found to be involved in cell cycle regulation, apoptosis and epithelial-mesenchymal transition. Altogether, micro RNAs seem to have an important role in the progression from gastritis to preneoplastic conditions and neoplastic lesions and since each micro RNA can control the expression of hundreds to thousands of genes, knowledge of micro RNAs target genes and their functions are of paramount importance. In this article we present a comprehensive review about the role of micro RNAs in H. pylori gastric carcinogenesis, identifying the micro RNAs downregulated and upregulated in the infection and clarifying their biological role in the link between immune host response, inflammation, DNA methylation and gastric carcinogenesis.

Community-Acquired Severe Sepsis:A Prospective Cohort Study

Severe sepsis (SS) is one of the principal causes of admission in intensive care units (ICU), with an associated high morbidity and mortality. This study intends to characterize epidemiology of community-acquired SS (CASS) with special emphasis in the prevalence of multidrug resistant organisms and independent prognostic factors associated with ICU mortality. Methods: A prospective cohort study was conducted over 3.5 years, including all consecutive adult patients with CASS admitted to a mixed ICU, in a 600-bed university-affiliated hospital. Results: 1221 patients were admitted into the ICU, 25% with CASS. The mean age was 59 years and the mean SAPS (simplified acute physiological score) was II 48. Most had septic shock (67%). Respiratory (57%), intra-abdominal (22%) and urinary tract (8%) infections were the main sources of infection. The overall isolation rate was 56%. The most common identified microorganisms were Streptococcus pneumoniae (27%), Escherichia coli (22%), Staphylococcus aureus methicillin sensitive (8%) and Haemophilus influenzae (7%). The median ICU and hospital length of stay were 8 and 16 days, respectively. The ICU mortality rate was 33. Independent risk factors associated with higher mortality were older age, higher SAPS II, septic shock and chronic hepatic disease. Female gender was independently associated with lower mortality. The type of microorganism was not significantly associated with prognosis. Conclusion: CASS was highly prevalent among ICU admissions. Independent risk factors associated with ICU mortality included older age and previous comorbidities, but mainly severity of acute illness reinforcing the need for early recognition and treatment. Multidrug resistant organisms were implicated in considerable proportion of community-acquired sepsis.