High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany

Abstract Background and aims Low-density lipoprotein cholesterol (LDL-C) is the main therapeutic target in the treatment of hypercholesterolemia. Small interfering RNA (siRNA) inclisiran is a new drug, which targets PCSK9 mRNA in the liver, reducing concentrations of circulating LDL-C. In randomized trials, inclisiran demonstrated a substantial reduction in LDL-C. The German Inclisiran Network (GIN) aims to evaluate LDL-C reductions in a real-world cohort of patients treated with inclisiran in Germany. Methods Patients who received inclisiran in 14 lipid clinics in Germany for elevated LDL-C levels between February 2021 and July 2022 were included in this analysis. We described baseline characteristics, individual LDL-C changes (%) and side effects in 153 patients 3 months (n = 153) and 9 months (n = 79) after inclisiran administration. Results Since all patients were referred to specialized lipid clinics, only one-third were on statin therapy due to statin intolerance. The median LDL-C reduction was 35.5% at 3 months and 26.5% at 9 months. In patients previously treated with PCSK9 antibody (PCSK9-mAb), LDL-C reductions were less effective than in PCSK9-mAb-naïve patients (23.6% vs. 41.1% at 3 months). Concomitant statin treatment was associated with more effective LDL-C lowering. There was a high interindividual variability in LDL-C changes from baseline. Altogether, inclisiran was well-tolerated, and side effects were rare (5.9%). Conclusion In this real-world patient population referred to German lipid clinics for elevated LDL-C levels, inclisiran demonstrated a high interindividual variability in LDL-C reductions. Further research is warranted to elucidate reasons for the interindividual variability in drug efficacy. Graphical abstrac

Recent in vitro findings of negative inotropy of pantoprazole did not translate into clinically relevant effects on left ventricular function in healthy volunteers

Reports on cardiac problems with oral proton pump inhibitors have caused extensive safety reviews by the US Food and Drug Administration. We provide additional data on acute cardiac effects of an intravenous application. Echocardiography was performed in 18 healthy volunteers after administration of a common high-dose regimen of pantoprazole (80 mg i.v. bolus followed by 8 mg/h for 1 h) or placebo. The design included a randomized, double-blind, placebo-controlled cross-over trial. Ejection fraction (%, mean +/- A SE) in the treatment group (placebo group) was 60.7 +/- A 1.1 (61.2 +/- A 1.7) at baseline, and 62.6 +/- A 1.1 (62.1 +/- A 1.9), 64.7 +/- A 1.6 (63.5 +/- A 1.3), 62.6 +/- A 1.6 (61.0 +/- A 1.6) and 63.0 +/- A 1.4 (61.8 +/- A 1.5) at 7.5, 15, 30 and 60 min after bolus application, respectively (p = n.s.). Similarly, no significant changes were found for cardiac output, cardiac index, blood pressure and heart rate. In contrast, gastric pH that was used as a treatment control was significantly increased 60 min after the application of pantoprazole as compared to baseline and to placebo. Pantoprazole as injection is safe in healthy subjects with respect to cardiac contractile function. However, in view of recent reports of negative inotropy of the drug, further studies in heart failure patients are required

A Spatial Distribution Study of Faunal Remains from Two Lower Magdalenian Occupation Levels in El Mirón Cave, Cantabria, Spain

Abstract: Human behaviour can be reconstructed by analysing specific activities and campsite organization using spatial analysis. The dense occupation layers of the Lower Cantabrian Magdalenian in the Northern Spain reveal varied aspects of Upper Palaeolithic lifeways, including evidence of specific localized activities. The outer vestibule of El Mirón cave has a particularly rich and intact Lower Magdalenian occupation horizon, Levels 15–17. The excavations in the outer vestibule “Cabin” area of the site revealed excellent bone preservation. Artefacts and faunal remains were individually recorded and sediments water-screened to yield a large sample of archaeological finds and spatial data. Zooarchaeological analysis provided the taxonomic, anatomic and taphonomic determination of the faunal individual finds. Smaller animal remains were categorized and counted; special attention was given to the identification of anthropogenic modifications such as burnt bones or bone flakes. These small refuse items are considered to be useful, in situ indicators of localized activities. The spatial distribution analysis of this dense and complex palimpsest of El Mirón Lower Cantabrian Magdalenian layers required GIS based methods including density analysis, heatmaps and cluster analysis. Based on the spatial distribution of Level 15 and 16 faunal remains, different activity areas were identified comprising hearth, working and dropping zones. These results imply the deliberately segregated use of space within the Lower Cantabrian Magdalenian site area, in which bone-processing activities played a central rol

Effects of Turbine Design on Particulate Erosion of Turbine Airfoils

An analytic study was conducted to determine the effects of turbine design, airfoil shape and material on particulate erosion of turbine airfoils in coal-fueled, direct-fired gas turbines used for electric power generation. First-stage, mean-line airfoil sections were designed for 80 MW output turbines with 3 and 4 stages. Two-dimensional particle trajectory calculations and erosion rate analyses were performed for a range of particle diameters and densities and for ductile and ceramic airfoil materials. Results indicate that the surface erosion rates can vary by a factor of 5 and that erosion on rotating blades is not well correlated with particle diameter. The results quantify the cause/effect turbine design relationships expected and assist in the selection of turbine design characteristics for use downstream of a coal-fueled combustion process.</jats:p

CHEST: Home of the Clinician-Educator

© 2017 Many hands can build a house; it takes trust to make that house a home. Trust has two main components: credibility (worthiness based on preparation and past performance) and empathy (the ability to understand and share another person\u27s values). CHEST has maintained its credibility and empathy as the global leader in clinical pulmonary, critical care, and sleep medical education. It follows that the leader in chest clinical education would also be the home of the clinician-educator. You are that educator