Anemia and chronic kidney disease are associated with poor outcomes in heart failure patients

BACKGROUND: Chronic kidney disease (CKD) has been linked to higher heart failure (HF) risk. Anemia is a common consequence of CKD, and recent evidence suggests that anemia is a risk factor for HF. The purpose of this study was to examine among patients with HF, the association between CKD, anemia and inhospital mortality and early readmission. METHODS: We performed a retrospective cohort study in two Swiss university hospitals. Subjects were selected based the presence of ICD-10 HF codes in 1999. We recorded demographic characteristics and risk factors for HF. CKD was defined as a serum creatinine ≥ 124 956;mol/L for women and ≥ 133 μmol/L for men. The main outcome measures were inhospital mortality and thirty-day readmissions. RESULTS: Among 955 eligible patients hospitalized with heart failure, 23.0% had CKD. Twenty percent and 6.1% of individuals with and without CKD, respectively, died at the hospital (p < 0.0001). Overall, after adjustment for other patient factors, creatinine and hemoglobin were associated with an increased risk of death at the hospital, and hemoglobin was related to early readmission. CONCLUSION: Both CKD and anemia are frequent among older patients with heart failure and are predictors of adverse outcomes, independent of other known risk factors for heart failure

A Modified RMCE-Compatible Rosa26 Locus for the Expression of Transgenes from Exogenous Promoters

Generation of gain-of-function transgenic mice by targeting the Rosa26 locus has been established as an alternative to classical transgenic mice produced by pronuclear microinjection. However, targeting transgenes to the endogenous Rosa26 promoter results in moderate ubiquitous expression and is not suitable for high expression levels. Therefore, we now generated a modified Rosa26 (modRosa26) locus that combines efficient targeted transgenesis using recombinase-mediated cassette exchange (RMCE) by Flipase (Flp-RMCE) or Cre recombinase (Cre-RMCE) with transgene expression from exogenous promoters. We silenced the endogenous Rosa26 promoter and characterized several ubiquitous (pCAG, EF1α and CMV) and tissue-specific (VeCad, αSMA) promoters in the modRosa26 locus in vivo. We demonstrate that the ubiquitous pCAG promoter in the modRosa26 locus now offers high transgene expression. While tissue-specific promoters were all active in their cognate tissues they additionally led to rare ectopic expression. To achieve high expression levels in a tissue-specific manner, we therefore combined Flp-RMCE for rapid ES cell targeting, the pCAG promoter for high transgene levels and Cre/LoxP conditional transgene activation using well-characterized Cre lines. Using this approach we generated a Cre/LoxP-inducible reporter mouse line with high EGFP expression levels that enables cell tracing in live cells. A second reporter line expressing luciferase permits efficient monitoring of Cre activity in live animals. Thus, targeting the modRosa26 locus by RMCE minimizes the effort required to target ES cells and generates a tool for the use exogenous promoters in combination with single-copy transgenes for predictable expression in mice

Two different dosing regimens of human recombinant erythropoietin beta during preoperative autologous blood donation in patients having hip arthroplasty

PURPOSE: Our aim was to evaluate the effectiveness of two different dosing regimens of human recombinant erythropoietin (rHu-EPO) for preoperative autologous blood collection in patients undergoing total hip arthroplasty (THA). ----- METHODS: Prospective randomised trials in which erythropoietin 15,000 IU was administered intravenously twice a week or 30,000 IU once a week (total 90,000 IU) combined with ferrous II sulphate (Ferro-Gradumet 2) orally and compared with Ferro-Gradumet 2 alone. ----- RESULTS: Although different dosing regimens of rHu-EPO administration during preoperative autologous blood donation have similar effects on the collection of two units of autologous blood, preoperative haemoglobin level and perioperative allogenic blood transfusion, a once weekly dose regimen of rHu-EPO was more convenient (although not statistically significantly) for patients. ----- CONCLUSION: We recommend the more practical and comfortable but yet highly effective therapeutic regimen with a single weekly intravenous administration of rHu-EPO for patients scheduled for THA