Effects of Eprosartan on Diastolic Function and Neurohormones in Patients with Hypertension and Diastolic Dysfunction

To compare the effects of an angiotensin receptor blocker(ARB)-based regimen versus a non-ARB based regimen on diastolic function and neurohormones in patients with hypertension and diastolic dysfunction. 97 patients with a systolic blood pressure (SBP) a parts per thousand yen140 mmHg, a left ventricular ejection fraction > 0.50, and echocardiographic evidence of diastolic dysfunction were randomly assignment to open-label treatment with eprosartan (with other anti-hypertensives; n = 47) or other anti-hypertensives alone (n = 50). Echocardiography, including tissue Doppler imaging (TDI), and neurohormones were done at baseline and after 6 months. Mean age was 65 (+/- 10) years and 64% was female. During 6 months of treatment, SBP decreased from 157 +/- 16 to 145 +/- 18 mmHg in the eprosartan group and from 158 +/- 17 to 141 +/- 18 mmHg in the control group (both p <0.001; p = ns between groups). Diastolic function was unaffected in both groups and there was no correlation between changes in SBP and changes in mean TDI (r = -0.06; p = 0.58). Aldosterone levels decreased in the eprosartan group, but other neurohormones remained largely unchanged. Change in SBP was however related to the change in NT-proBNP (r = 0.26; p = 0.019). Lowering blood pressure, either with eprosartan or other anti-hypertensives in hypertensive patients with diastolic dysfunction did not change diastolic function after 6 months of treatment, but was associated with a decrease of NT-proBNP

Human monoclonal antibodies against Staphylococcus aureus surface antigens recognize in vitro and in vivo biofilm

Implant-associated Staphylococcus aureus infections are difficult to treat because of biofilm formation. Bacteria in a biofilm are often insensitive to antibiotics and host immunity. Monoclonal antibodies (mAbs) could provide an alternative approach to improve the diagnosis and potential treatment of biofilm-related infections. Here, we show that mAbs targeting common surface components of S. aureus can recognize clinically relevant biofilm types. The mAbs were also shown to bind a collection of clinical isolates derived from different biofilm-associated infections (endocarditis, prosthetic joint, catheter). We identify two groups of antibodies: one group that uniquely binds S. aureus in biofilm state and one that recognizes S. aureus in both biofilm and planktonic state. Furthermore, we show that a mAb recognizing wall teichoic acid (clone 4497) specifically localizes to a subcutaneously implanted pre-colonized catheter in mice. In conclusion, we demonstrate the capacity of several human mAbs to detect S. aureus biofilms in vitro and in vivo

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

A roadmap towards quantitative cumulative impact assessments : Every step of the way

Currently most Cumulative Impacts Assessments (CIAs) are risk-based approaches that assess the potential impact of human activities and their pressures on the ecosystem thereby compromising the achievement of policy objectives. While some of these CIAs apply actual data (usually spatial distributions) they often have to rely on categorical scores based on expert judgement if they actually assess impact which is often expressed as a relative measure that is difficult to interpret in absolute terms. Here we present a first step-wise approach to conduct a fully quantitative CIA based on the selection and subsequent application of the best information available. This approach systematically disentangles risk into its exposure and effect components that can be quantified using known ecological information, e.g. spatial distribution of pressures or species, pressure-state relationships and population dynamics models with appropriate parametrisation, resulting in well-defined assessment endpoints that are meaningful and can be easily communicated to the recipients of advice. This approach requires that underlying assumptions and methodological considerations are made explicit and translated into a measure of confidence. This transparency helps to identify the possible data-handling or methodological decisions and shows the resulting improvement through its confidence assessment of the applied information and hence the resulting accuracy of the CIA. To illustrate this approach, we applied it in a North Sea CIA focussing on two sectors, i.e. fisheries and offshore windfarms, and how they impact the ecosystem and its components, i.e. seabirds, seabed habitats and marine mammals through various pressures. The results provide a “proof of concept” for this generic approach as well as rigorous definitions of several of the concepts often used as part of risk-based approaches, e.g. exposure, sensitivity, vulnerability, and how these can be estimated using actual data. As such this widens the scope for increasingly more quantitative CIAs using the best information available.</p

Intravascular Lipiodol Presenting as an Atrial Mass

A 68-year-old woman, previously treated with embolization of the thoracic duct with Lipiodol (an ethiodized oil injection) and cyanoacrylate glue (a topical tissue adhesive), was admitted with an asymptomatic mass in the inferior vena cava (IVC) and right atrium. The mass was surgically removed, and pathologic analysis revealed a Lipiodol-containing thrombus. To our knowledge, this is the first clinicopathologic report of Lipiodol-induced thrombus presenting as an intracavitary mass. (C) 2017 by The Society of Thoracic Surgeon

Predictors of angiotensin-converting enzyme inhibitor - Induced reduction of urinary albumin excretion in nondiabetic patients

Urinary albumin excretion is a predictor for cardiovascular mortality and morbidity. We investigated which parameters determine baseline urinary albumin excretion in nondiabetic subjects, without renal disease. In addition, we evaluated the parameters that predict the albuminuria-lowering efficacy of an angiotensin-converting enzyme inhibitor. In this substudy of the Prevention of Renal and Vascular Endstage Disease Intervention Trial, 384 microalbuminuric patients were included. Patient and biochemical characteristics were obtained at baseline and after 3 months of double-blinded, randomized treatment (fosinopril 20 mg or placebo). Mean age was 51.1 +/- 11.5 years, and 65.6% were male. Median urinary albumin excretion was 22.2 mg per 24 hours. At baseline, mean arterial pressure (beta(standardized) = 0.161; P = 0.006), urinary sodium excretion (beta(standardized) = 0.154; P = 0.011), and estimated renal function were independently associated with albumin excretion. In these predominantly normotensive to prehypertensive subjects, fosinopril reduced albumin excretion by 18.5% versus a 6.1% increase on placebo after 3 months (P <0.001). Fosinopril use and blood pressure reduction independently predicted the change in urinary albumin excretion. Baseline urinary albumin excretion independently predicted the antialbuminuric effect of fosinopril (beta(standardized) = -0.303; P <0.001). In conclusion, at baseline, sodium intake and blood pressure were positively associated with urinary albumin excretion. Fosinopril reduced albuminuria more than might be expected from its blood pressure - lowering effect alone, and this effect was more outspoken in subjects with higher baseline albumin excretion. Based on our data, we hypothesize that angiotensin-converting enzyme inhibition may result in superior cardiovascular protection when compared with other blood pressure-lowering agents in subjects with higher baseline levels of albuminuria

Plasma matrix metalloproteinase-9 and ACE-inhibitor-induced improvement of urinary albumin excretion in non-diabetic, microalbuminuric subjects

Introduction. Elevated plasma matrix metalloproteinase-9 (MMP-9) levels have been suggested to precede the development of microalbuminuria. As angiotensin-converting enzyme (ACE) inhibitors effectively reduce urinary albumin excretion (UAE), in the present study we have investigated the potential association of plasma MMP-9 levels with UAE and treatment effects of ACE-inhibition. Material and methods. In a placebo-controlled randomised trial we determined plasma MMP-9 levels at baseline and after three months of randomisation to either placebo (n=202) or fosinopril (20 mg/day, n=204) treatment. Results. Baseline plasma MMP-9 levels were not related to baseline UAE (r=-0.008, p=0.871). Three months of fosinopril treatment effectively reduced UAE compared to placebo treatment (-10.4 +/- 2.4 vs. 1.8 +/- 1.3 mg/24 hours, p Conclusion. The effective reduction of UAE with fosinopril was not related to plasma MMP-9 levels