These data indicate that sepsis survivors had substantially increased risks of subsequent all-cause mortality and major adverse cardiovascular events at 1 year after discharge, which persisted for up to 5 years after discharge.
Background-Whether oral anticoagulant use should be considered in patients undergoing hemodialysis with atrial fibrillation (AF) remains controversial because of the uncertainty regarding risk-benefit assessments. , and hospitalization for heart failure (aHR, 1.90; 95% CI, 1.76-2.05). After considering in-hospital death as a competing risk, AF significantly increased the risk of heart failure (HR, 1.56; 95% CI, 1.45-1.68), but not those of ischemic stroke and myocardial infarction. Additionally, the predictive value of the CHA 2 DS 2 -VASc score for ischemic stroke was diminished in the competing-risk model. Conclusions-The risk of stroke was only modestly higher in patients undergoing hemodialysis with new-onset AF than in those without AF, and it became insignificant when accounting for the competing risk of in-hospital death.
Although oral antidiabetic drugs (OADs) have been associated with immunomodulation in preclinical studies, little is still known about the association between the use of OADs and the risk of sepsis. Using a cohort of patients, extracted from Taiwan’s National Health Insurance Research Database, with type 2 diabetes who were newly diagnosed between 2010 and 2012 and treated with OADs, we conducted a nested case-control study involving 43,015 cases (patients who were first hospitalized for sepsis) and 43,015 matched controls. Compared with non-use, metformin use was associated with a decreased risk of developing sepsis (adjusted odds ratio [OR] 0.80, 95% confidence interval [CI] 0.77–0.83, P < 0.001), but meglitinide (adjusted OR 1.32, 95% CI 1.25–1.40, P < 0.001) use was associated with the increased risk of developing sepsis. The risk for development of sepsis was also lower among current (adjusted OR 0.87, 95% CI 0.78–0.96) and recent (adjusted OR 0.83, 95% CI 0.73–0.94) thiazolidinedione users. Current or recent sulfonylurea use and dipeptidyl peptidase-4 inhibitor use were not significantly associated with the development of sepsis. Our results highlight the need to consider the potential pleiotropic effect of OADs against sepsis in addition to the lowering of blood glucose.
Background
A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored.
Methods
We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium.
Results
Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 (conditional p = 2.51 × 10−4; OR = 1.04; 95% CI 1.02–1.07) and rs77928427 (p = 1.86 × 10−4; OR = 1.04; 95% CI 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue.
Conclusion
Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2.
Impact
Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.
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