Acute kidney injury in Staphylococcus aureus bacteremia: a recurrent events analysis.

OBJECTIVES: To estimate risk factors for AKI and the effect of AKI on mortality in Staphylococcus aureus bacteremia, while taking into account recurrent AKI episodes, competing risks, time-varying variables and time-varying effects. METHODS: We performed an unplanned analysis using data from a multicenter cohort study of patients with SAB. Primary outcome was cumulative incidence of AKI, according to KDIGO definitions. RESULTS: We included 453 patients in this study of whom 194 (43%) patients experienced one or more AKI episodes. Age (HR 1.013, 95% CI 1.001 - 1.024), Charlson comorbidity index (HR 1.07, 95% CI 1.01 - 1.14), prior chronic kidney disease (HR 1.76, 95% CI 1.28 - 2.42), septic shock (HR 3.28, 95% CI 2.31 - 4.66), persistent bacteremia (HR 1.53, 95% CI 1.08 - 2.17) and vancomycin therapy (HR 1.80, 95% CI 1.05 - 3.09) were independently associated with AKI, but flucloxacillin, cefazolin, rifampicin and aminoglycoside therapy were not. After adjustment for confounders and immortal time bias, AKI was associated with an increased risk of 90-day mortality (HR 4.26, 95% CI 2.91 - 6.23). CONCLUSIONS: Incidence of AKI in SAB is high and a substantial proportion of patients develops recurrent episodes of AKI after recovery. AKI is specifically linked to the use of vancomycin and not to anti-staphylococcal penicillins. Clinical outcome of patients with SAB complicated by AKI is worse than previously estimated.

Intestinal cholesterol secretion: future clinical implications.

Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues in the body to the faeces. In humans, faecal cholesterol elimination via the RCT pathway is considered to be restricted to excretion via the hepatobiliary route. Recently, however, direct trans-intestinal excretion of plasma-derived cholesterol (TICE) was shown to contribute substantially to faecal neutral sterol (FNS) excretion in mice. TICE was found to be amenable to stimulation by various pharmacological and dietary interventions in mice, offering new options to target the intestine as an inducible, cholesterol-excretory organ. The relevance of TICE for cholesterol elimination in humans remains to be established. There is, however, emerging evidence for the presence of TICE in human (patho) physiology. This review discusses our current understanding of TICE and its novel therapeutic potential for individuals at increased risk of cardiovascular disease.

Baseline cholesterol absorption and the response to ezetimibe/simvastatin therapy: a post-hoc analysis of the ENHANCE trial.

Subjects with increased cholesterol absorption might benefit more from statin therapy combined with a cholesterol absorption inhibitor. We assessed whether baseline cholesterol absorption markers were associated with response to ezetimibe/simvastatin therapy, in terms of LDL-cholesterol (LDL-C) lowering and cholesterol absorption inhibition, in patients with familial hypercholesterolemia (FH). In a posthoc analysis of the two-year ENHANCE trial, we assessed baseline cholesterol-adjusted campesterol (campesterol/TC) and sitosterol/TC ratios in 591 FH patients. Associations with LDL-C changes and changes in cholesterol absorption markers were evaluated by multiple regression analysis. No association was observed between baseline markers of cholesterol absorption and the extent of LDL-C response to ezetimibe/simvastatin therapy (beta = 0.020, P = 0.587 for campesterol/TC and beta<0.001, P = 0.992 for sitosterol/TC). Ezetimibe/simvastatin treatment reduced campesterol levels by 68% and sitosterol levels by 62%; reductions were most pronounced in subjects with the highest cholesterol absorption markers at baseline, the so-called high absorbers (P < 0.001). Baseline cholesterol absorption status does not determine LDL-C lowering response to ezetimibe/simvastatin therapy in FH, despite more pronounced cholesterol absorption inhibition in high absorbers. Hence, these data do not support the use of baseline absorption markers as a tool to determine optimal cholesterol lowering strategy in FH patients. However, due to the exploratory nature of any posthoc analysis, these results warrant further prospective evaluation in different populations.