Amino acid profile in malnourished patients with liver cirrhosis and its modification with oral nutritional supplements: Implications on minimal hepatic encephalopathy

Low plasma levels of branched chain amino acids (BCAA) in liver cirrhosis are associated with hepatic encephalopathy (HE). We aimed to identify a metabolic signature of minimal hepatic encephalopathy (MHE) in malnourished cirrhotic patients and evaluate its modification with oral nutritional supplements (ONS) enriched with ß-Hydroxy-ß-methylbutyrate (HMB), a derivative of the BCAA leucine. Post hoc analysis was conducted on a double-blind placebo-controlled trial of 43 individuals with cirrhosis and malnutrition, who were randomized to receive, for 12 weeks, oral supplementation twice a day with either 220 mL of Ensure® Plus Advance (HMB group, n = 22) or with 220 mL of Ensure® Plus High Protein (HP group, n = 21). MHE evaluation was by psychometric hepatic encephalopathy score (PHES). Compared to the HP group, an HMB-specific treatment effect led to a larger increase in Val, Leu, Phe, Trp and BCAA fasting plasma levels. Both treatments increased Fischer’s ratio and urea without an increase in Gln or ammonia fasting plasma levels. MHE was associated with a reduced total plasma amino acid concentration, a reduced BCAA and Fischer´s ratio, and an increased Gln/Glu ratio. HMB-enriched ONS increased Fischer´s ratio without varying Gln or ammonia plasma levels in liver cirrhosis and malnutrition, a protective amino acid profile that can help prevent MHE. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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The Compact Linear Collider (CLIC) - 2018 Summary Report

The Compact Linear Collider (CLIC) is a TeV-scale high-luminosity linear $e^+e^-$ collider under development at CERN. Following the CLIC conceptual design published in 2012, this report provides an overview of the CLIC project, its current status, and future developments. It presents the CLIC physics potential and reports on design, technology, and implementation aspects of the accelerator and the detector. CLIC is foreseen to be built and operated in stages, at centre-of-mass energies of 380 GeV, 1.5 TeV and 3 TeV, respectively. CLIC uses a two-beam acceleration scheme, in which 12 GHz accelerating structures are powered via a high-current drive beam. For the first stage, an alternative with X-band klystron powering is also considered. CLIC accelerator optimisation, technical developments and system tests have resulted in an increased energy efficiency (power around 170 MW) for the 380 GeV stage, together with a reduced cost estimate at the level of 6 billion CHF. The detector concept has been refined using improved software tools. Significant progress has been made on detector technology developments for the tracking and calorimetry systems. A wide range of CLIC physics studies has been conducted, both through full detector simulations and parametric studies, together providing a broad overview of the CLIC physics potential. Each of the three energy stages adds cornerstones of the full CLIC physics programme, such as Higgs width and couplings, top-quark properties, Higgs self-coupling, direct searches, and many precision electroweak measurements. The interpretation of the combined results gives crucial and accurate insight into new physics, largely complementary to LHC and HL-LHC. The construction of the first CLIC energy stage could start by 2026. First beams would be available by 2035, marking the beginning of a broad CLIC physics programme spanning 25-30 years

Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project.

Purpose: To achieve clinical validation of cutoff values for newborn screening by tandem mass 215 spectrometry through a worldwide collaboration. Methods: Cumulative percentiles of amino 216 acids and acylcarnitines in dried blood spots of approximately 30 million normal newborns and 217 10,615 true positive cases are compared to assign clinical significance, which is achieved when 218 the median of a disease range is either >99%ile or <1%ile of the normal population. The cutoff 219 target ranges of analytes and ratios are then defined as the interval between the limits of the two 220 populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity 221 taking in consideration all available factors. Results: As of December 1, 2010, 129 sites in 45 222 countries have uploaded to the project website a total of 23,970 percentile data points, 558,168 223 analyte results of 10,615 true positive cases with 64 conditions, and 5,088 cutoff values. The 224 average rate of submission of true positive cases between December 1, 2008 and December 1, 225 2010 was 4.7 cases per day (3,418 cases). This cumulative evidence generated 91 and 23 high 226 and low target cutoff ranges, respectively. The overall proportion of cutoff values within the 227 respective target range was 43% (2,176/5,088). Conclusions: An unprecedented level of 228 cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 229 markers applied to newborn screening of rare metabolic disorders. This set of data could be used 230 as baseline for monitoring of future performance