Genome-Wide Comparison of Next-Generation Sequencing and qPCR Platforms for microRNA Profiling in Serum.

This study compares next-generation sequencing (NGS) technologies that have been optimized specifically for biofluid samples, with more established qPCR-based methods for profiling microRNAs in biofluids. The same patient serum samples were analyzed by NGS and qPCR, and differences in the serum microRNA profile between HBV and HCV infected patients were investigated. While there was overall good agreement between NGS and qPCR, there were some differences between the platforms, highlighting the importance of validation.

Post-operative acute kidney injury and five-year risk of death, myocardial infarction, and stroke among elective cardiac surgical patients: a cohort study.

INTRODUCTION: The prognostic impact of acute kidney injury (AKI) on long-term clinical outcomes remains controversial. We examined the five-year risk of death, myocardial infarction, and stroke after elective cardiac surgery complicated by AKI. METHODS: We conducted a cohort study among adult elective cardiac surgical patients without severe chronic kidney disease and/or previous heart or renal transplant surgery using data from population-based registries. AKI was defined by the Acute Kidney Injury Network (AKIN) criteria as a 50% increase in serum creatinine from baseline level, acute creatinine rise of ≥26.5 µmol/L (0.3 mg/dL) within 48 hours, and/or initiation of renal replacement therapy within five days after surgery. We followed patients from the fifth post-operative day until myocardial infarction, stroke or death within five years. Five-year risk was computed by the cumulative incidence method and compared with hazards ratios (HR) from a Cox proportional hazards regression model adjusting for propensity score. RESULTS: A total of 287 (27.9%) of 1,030 patients developed AKI. Five-year risk of death was 26.5% (95% CI: 21.2 to 32.0) among patients with AKI and 12.1% (95% CI: 10.0 to 14.7) among patients without AKI. The corresponding adjusted HR of death was 1.6 (95% CI: 1.1 to 2.2). Five-year risk of myocardial infarction was 5.0% (95% CI: 2.9 to 8.1) among patients with AKI and 3.3% (95% CI: 2.1 to 4.8) among patients without AKI. Five-year risk of stroke was 5.0% (95% CI: 2.8 to 7.9) among patients with AKI and 4.2% (95% CI: 2.9 to 5.8) among patients without AKI. Adjusted HRs were 1.5 (95% CI: 0.7 to 3.2) of myocardial infarction and 0.9 (95% CI: 0.5 to 1.8) of stroke. CONCLUSIONS: AKI, within five days after elective cardiac surgery, was associated with increased five-year mortality and a statistically insignificant increased risk of myocardial infarction. No association was seen with the risk of stroke.

The EuroSCORE in western Denmark: a population-based study.

OBJECTIVE: The present study aimed to examine the predictive performance of the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) in a large cohort of patients undergoing cardiac surgery from 1999 through 2010 because methodologic shortcomings have hampered many previous studies questioning its predictive performance. DESIGN: Population-based prospectively registered data. SETTING: The Western Denmark Heart Registry, a multi-institutional registry. PARTICIPANTS: Twenty-one thousand six hundred sixty-four patients. INTERVENTIONS: On-pump cardiac surgery. MEASUREMENTS AND MAIN RESULTS: The predictive ability of the logistic EuroSCORE was assessed using the area under the curve (AUC) for the discrimination test, the Hosmer-Lemeshow (HL) calibration test, and the mean estimated-to-observed mortality ratio (E/O). The overall AUC was 0.79 (95% confidence interval [CI] 0.77-0.81; HL test, p < 0.01; E/O 1.9). For coronary artery bypass grafting, the AUC was 0.78 (95% CI 0.75-0.81; HL test, p < 0.01; E/O 2.3). For coronary artery bypass grafting plus valve replacement, the AUC was 0.69 (95% CI 0.65-0.73; HL test, p = 0.02; E/O 1.5). For aortic valve replacement, the AUC was 0.76 (95% CI 0.72-0.80; HL test, p < 0.01; E/O 2.5). The overall and procedural specific E/O ratios tended to increase from 1999 to 2010. Mortality was overestimated across all levels of estimated risk, and in low-to-medium-risk patients, this overestimation increased most notably with time. CONCLUSIONS: The EuroSCORE provides moderate-to-good discrimination and poor calibration. Despite substantial changes in risk factors during the study period, the EuroSCORE consistently overestimated 30-day mortality independent of the preoperative risk level and surgical procedure performed, indicating improved quality of surgery and patient care.

Microalbuminuria is associated with high adverse event rate following cardiac surgery.

OBJECTIVE: To examine if preoperative microalbuminuria is associated with an increased risk of long-term adverse outcomes following elective cardiac surgery and if it provides additional prognostic information beyond the European System for Cardiac Operative Risk Evaluation (EuroSCORE). METHODS: In a prospective follow-up study, we included 1049 patients undergoing elective cardiac surgery from 1 April 2005 to 30 September 2007. Microalbuminuria (urine albumin/creatinine ratio between 2.5 and 25 mg mmol(-1)) was assessed preoperatively in a morning spot-urine sample. We used population-based medical registries for follow-up from day 31 until day 365 postoperatively, and compared all-cause death, myocardial infarction, cerebral stroke and a composite outcome of severe infections including septicaemia, deep or superficial sternal wound infection, or leg wound infection among patients with or without microalbuminuria using Cox proportional hazard and competing risk regressions. RESULTS: Microalbuminuria was found in 175 (18.5%) out of 947 patients available for follow-up. The adjusted risks of all-cause death (adjusted hazard ratio 2.3 (95% confidence interval 1.1-4.9)), stroke (adjusted hazard ratio 2.9 (95% confidence interval 1.1-7.8)) and severe infection composite outcome (adjusted hazard ratio 2.4 (95% confidence interval 1.2-4.9)) were doubled to tripled in patients with preoperative microalbuminuria. The risk of myocardial infarction was not increased. Adding information on microalbuminuria improved the predictive accuracy of the EuroSCORE regarding mortality (areas under receiver operating characteristic curves were: for the EuroSCORE 0.73 (95% confidence interval 0.65-0.81) and for EuroSCORE+microalbuminuria 0.76 (95% confidence interval 0.68-0.83). CONCLUSIONS: Preoperative microalbuminuria is associated with an increased risk of long-term adverse outcomes in patients undergoing elective cardiac surgery, and it appears to provide prognostic information on mortality.

No excess surgical blood loss in patients with acquired type 2A von Willebrand disease.

OBJECTIVES: Acquired type 2A von Willebrand disease may develop as a consequence of aortic valve stenosis and is associated with varying degrees of bleeding tendency. It remains unknown, whether it portends excess blood loss during aortic valve replacement. DESIGN: We consecutively enrolled 45 patients with severe aortic valve stenosis undergoing aortic valve replacement. Patients with acquired type 2A von Willebrand disease were identified measuring the von Willebrand factor high molecular weight multimer. Data on the intraoperative, early postoperative, and the total blood loss within 24 hours of surgery was obtained and compared between groups. RESULTS: Acquired type 2A von Willebrand disease was found in 33% (n = 15/45) of the patients. Baseline characteristics were similar between groups. Patients with acquired type 2A von Willebrand disease neither had excess median intraoperative blood loss (375 ml (interquartile range 100-450 ml) vs. 350 ml (interquartile range 250-500 ml), p = 0.59) nor increased median total blood loss (695 ml (interquartile range 450-850 ml) vs. 752 ml (interquartile range 575-1035 ml), p = 0.41) as compared to patients without acquired type 2A von Willebrand disease. CONCLUSION: Acquired type 2A von Willebrand disease was not associated with increased blood loss during aortic valve replacement in patients with severe aortic valve stenosis.

Insulin resistance, adiponectin and adverse outcomes following elective cardiac surgery: a prospective follow-up study.

BACKGROUND: Insulin resistance and adiponectin are markers of cardio-metabolic disease and associated with adverse cardiovascular outcomes. The present study examined whether preoperative insulin resistance or adiponectin were associated with short- and long-term adverse outcomes in non-diabetic patients undergoing elective cardiac surgery. METHODS: In a prospective study, we assessed insulin resistance and adiponectin levels from preoperative fasting blood samples in 836 patients undergoing cardiac surgery. Population-based medical registries were used for postoperative follow-up. Outcomes included all-cause death, myocardial infarction or percutaneous coronary intervention, stroke, re-exploration, renal failure, and infections. The ability of insulin resistance and adiponectin to predict clinical adverse outcomes was examined using receiver operating characteristics. RESULTS: Neither insulin resistance nor adiponectin were statistically significantly associated with 30-day mortality, but adiponectin was associated with an increased 31-365-day mortality (adjusted odds ratio 2.9 [95% confidence interval 1.3-6.4]) comparing the upper quartile with the three lower quartiles. Insulin resistance was a poor predictor of adverse outcomes. In contrast, the predictive accuracy of adiponectin (area under curve 0.75 [95% confidence interval 0.65-0.85]) was similar to that of the EuroSCORE (area under curve 0.75 [95% confidence interval 0.67-0.83]) and a model including adiponectin and the EuroSCORE had an area under curve of 0.78 [95% confidence interval 0.68-0.88] concerning 31-365-day mortality. CONCLUSIONS: Elevated adiponectin levels, but not insulin resistance, were associated with increased mortality and appear to be a strong predictor of long-term mortality. Additional studies are warranted to further clarify the possible clinical role of adiponectin assessment in cardiac surgery. TRIAL REGISTRATION: The Danish Data Protection Agency; reference no. 2007-41-1514.

Microalbuminuria and short-term prognosis in patients undergoing cardiac surgery.

OBJECTIVES: To examine if preoperative microalbuminuria (MA) is associated with in increased risk of adverse outcomes in patients undergoing elective cardiothoracic surgery, and if adding information on MA could improve the accuracy of the additive EuroSCORE. METHODS: In a follow-up study we included 962 patients undergoing elective cardiothoracic surgery from 1 April 2005 to 30 September 2007 at our department. MA (urine albumin/creatinine ratio between 2.5-25 mg/mmol) was assessed in a morning spot-urine sample. We used population-based medical registries for 30-day follow-up and compared the length of stay and adverse outcomes including (i) all-cause death, myocardial infarction, stroke, or atrial fibrillation, (ii) surgical reintervention, renal insufficiency, sternal wound infection, or septicaemia among patients with and without MA. RESULTS: MA was found in 180 (18.7%) patients. The risk of both combined outcomes (adjusted odds ratios (ORs): 1.00 (95% confidence interval (CI): 0.77-1.30) and 1.18 (95% CI: 0.79-1.75), respectively) and most individual outcomes did not differ between the micro- and normoalbuminuric patients. The patients with MA and an additive EuroSCORE of 5 had a significantly prolonged median length of intensive care unit (ICU) stay (0.15 days [95% CI: 0.04-0.26]) and total hospital stay (0.5 days [95% CI: 0.04-0.96]). Patients with MA had a higher risk of postoperative septicaemia (OR: 12.1 [95% CI: 3.2-45.9]). Area under receiver operating characteristics curves of the EuroSCORE with regard to 30-day mortality was 0.86 both with and without MA. CONCLUSIONS: Preoperative MA in patients undergoing elective cardiothoracic surgery was not associated with most early adverse outcomes. However, risk of septicaemia was higher and patients with MA also had a marginally longer length of ICU and hospital stay. Information on preoperative MA did not improve the accuracy of the additive EuroSCORE.

Practical regimen for amiodarone use in preventing postoperative atrial fibrillation.

BACKGROUND: Postoperative atrial fibrillation occurs in 5% to 65% of patients undergoing cardiac surgery. Although postoperative atrial fibrillation is often regarded as a temporary, benign, operation-related problem, it is associated with a twofold to threefold increase in risk of adverse events, including permanent or transient stroke, acute myocardial infarction, and death. METHODS: This randomized, controlled, double-blinded trial included 250 eligible consecutively enrolled patients undergoing coronary artery bypass grafting (CABG). They received 300 mg of amiodarone/placebo administered intravenously over 20 minutes on the first postoperative day and an oral dose of 600 mg of amiodarone or placebo twice daily for the first 5 postoperative days. RESULTS: The patients in amiodarone prophylaxis experienced a reduction in risk of atrial fibrillation of 14% (95% confidence interval [CI], 5.0% to 24%), with the number needed to treat at 6.9 (95% CI, 4.2 to 20), and the results for symptomatic atrial fibrillation showed a risk reduction of 18% (95% CI, 9.4% to 26), with the number needed to treat at 5.7 (95% CI, 3.9 to 11). Of the patients who developed atrial fibrillation in the placebo group, 84% experienced a symptomatic attack versus only 43% in the amiodarone group. CONCLUSIONS: Postoperative prophylaxis with a high dose of oral amiodarone after an intravenous bolus infusion is a safe, practical, feasible, and effective regimen for CABG patients. It significantly diminishes the occurrence of postoperative atrial fibrillation.