Circulating adrenomedullin in cirrhosis: relationship to hyperdynamic circulation

BACKGROUND/AIMS: Peripheral arterial vasodilation may be the key factor in the sodium and water retention of cirrhosis. The mechanism responsible for this vasodilation remains to be fully elucidated. Adrenomedullin is a novel peptide, highly expressed in cardiovascular tissues, with potent and long-lasting vasodilating activity. METHODS: The possible implication of adrenomedullin in the hemodynamic changes of cirrhosis has been investigated. We measured the plasma concentration of adrenomedullin in 20 cirrhotic patients and 11 healthy subjects. In addition, systemic, portal and renal hemodynamics, hormonal factors and renal function parameters were evaluated in the same patients. RESULTS: Circulating adrenomedullin was significantly higher in the group of patients with cirrhosis (72.1; 46-100 vs 21.6; 11-34 fmol/dl, respectively; p<0.02) and was directly correlated with the Pugh score (r: 0.6; p: 0.01), inversely correlated with the creatinine clearance (r: -0.6; p<0.01) and tended to inversely correlate with systemic vascular resistance index (r: -0.46; p: 0.07). There were no portal-peripheral differences in adrenomedullin levels. Transjugular intrahepatic portosystemic shunt insertion did not induce changes in the peripheral concentration of adrenomedullin, but baseline values of this hormone predicted the degree of hyperdynamic circulation after TIPS. CONCLUSIONS: Circulating adrenomedullin is increased in cirrhosis. These levels increase with the severity of the disease, especially in patients with hepatorenal syndrome. This peptide may contribute to vasodilation of cirrhosis

Brucellosis Vaccines: Assessment of Brucella melitensis Lipopolysaccharide Rough Mutants Defective in Core and O-Polysaccharide Synthesis and Export

Background: The brucellae are facultative intracellular bacteria that cause brucellosis, one of the major neglected zoonoses. In endemic areas, vaccination is the only effective way to control this disease. Brucella melitensis Rev 1 is a vaccine effective against the brucellosis of sheep and goat caused by B. melitensis, the commonest source of human infection. However, Rev 1 carries a smooth lipopolysaccharide with an O-polysaccharide that elicits antibodies interfering in serodiagnosis, a major problem in eradication campaigns. Because of this, rough Brucella mutants lacking the O-polysaccharide have been proposed as vaccines. Methodology/Principal Findings: To examine the possibilities of rough vaccines, we screened B. melitensis for lipopolysaccharide genes and obtained mutants representing all main rough phenotypes with regard to core oligosaccharide and O-polysaccharide synthesis and export. Using the mouse model, mutants were classified into four attenuation patterns according to their multiplication and persistence in spleens at different doses. In macrophages, mutants belonging to three of these attenuation patterns reached the Brucella characteristic intracellular niche and multiplied intracellularly, suggesting that they could be suitable vaccine candidates. Virulence patterns, intracellular behavior and lipopolysaccharide defects roughly correlated with the degree of protection afforded by the mutants upon intraperitoneal vaccination of mice. However, when vaccination was applied by the subcutaneous route, only two mutants matched the protection obtained with Rev 1 albeit at doses one thousand fold higher than this reference vaccine. These mutants, which were blocked in O-polysaccharide export and accumulated internal O-polysaccharides, stimulated weak anti-smooth lipopolysaccharide antibodies. Conclusions/Significance: The results demonstrate that no rough mutant is equal to Rev 1 in laboratory models and question the notion that rough vaccines are suitable for the control of brucellosis in endemic areas.This work was funded by the European Commission (Research Contract QLK2-CT-2002-00918) and the Ministerio de Ciencia y Tecnología of Spain (Proyecto AGL2004-01162/GAN)

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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Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Circulating adrenomedullin in cirrhosis: relationship to hyperdynamic circulation

BACKGROUND/AIMS: Peripheral arterial vasodilation may be the key factor in the sodium and water retention of cirrhosis. The mechanism responsible for this vasodilation remains to be fully elucidated. Adrenomedullin is a novel peptide, highly expressed in cardiovascular tissues, with potent and long-lasting vasodilating activity. METHODS: The possible implication of adrenomedullin in the hemodynamic changes of cirrhosis has been investigated. We measured the plasma concentration of adrenomedullin in 20 cirrhotic patients and 11 healthy subjects. In addition, systemic, portal and renal hemodynamics, hormonal factors and renal function parameters were evaluated in the same patients. RESULTS: Circulating adrenomedullin was significantly higher in the group of patients with cirrhosis (72.1; 46-100 vs 21.6; 11-34 fmol/dl, respectively; p<0.02) and was directly correlated with the Pugh score (r: 0.6; p: 0.01), inversely correlated with the creatinine clearance (r: -0.6; p<0.01) and tended to inversely correlate with systemic vascular resistance index (r: -0.46; p: 0.07). There were no portal-peripheral differences in adrenomedullin levels. Transjugular intrahepatic portosystemic shunt insertion did not induce changes in the peripheral concentration of adrenomedullin, but baseline values of this hormone predicted the degree of hyperdynamic circulation after TIPS. CONCLUSIONS: Circulating adrenomedullin is increased in cirrhosis. These levels increase with the severity of the disease, especially in patients with hepatorenal syndrome. This peptide may contribute to vasodilation of cirrhosis

Photometric redshifts and clustering of emission line galaxies selected jointly by DES and eBOSS

We present the results of the first observations of the emission line galaxies (ELG) of the extended Baryon Oscillation Spectroscopic Survey. From the total 9000 targets, 4600 have been selected from the Dark Energy Survey (DES). In this subsample, the total success rate for redshifts between 0.6 and 1.2 is 71 and 68 per cent for a bright and a faint samples, respectively, including redshifts measured from a single strong emission line. The mean redshift is 0.80 for the bright and 0.87 for the faint sample, while the percentage of unknown redshifts is 15 and 13 per cent, respectively. In both cases, the star contamination is lower than 2 per cent. We evaluate how well the ELG redshifts are measured using the target selection photometry and validating with the spectroscopic redshifts measured by eBOSS. We explore different techniques to reduce the photometric redshift outliers fraction with a comparison between the template fitting, the neural networks and the random forest methods. Finally, we study the clustering properties of the DES SVA1 ELG samples. We select only the most secure spectroscopic redshift in the redshift range 0.6 < z < 1.2, leading to a mean redshift for the bright and faint sample of 0.85 and 0.90, respectively. We measure the projected angular correlation function and obtain a galaxy bias averaging on scales from 1 to 10 Mpc h−1 of 1.58 ± 0.10 for the bright sample and 1.65 ± 0.12 for the faint sample. These values are representative of a galaxy population with MB − log(h) < −20.5, in agreement with what we measure by fitting galaxy templates to the photometric data

Photometric redshifts and clustering of emission line galaxies selected jointly by DES and eBOSS

We present the results of the first observations of the emission line galaxies (ELG) of the extended Baryon Oscillation Spectroscopic Survey. From the total 9000 targets, 4600 have been selected from the Dark Energy Survey (DES). In this subsample, the total success rate for redshifts between 0.6 and 1.2 is 71 and 68 per cent for a bright and a faint samples, respectively, including redshifts measured from a single strong emission line. The mean redshift is 0.80 for the bright and 0.87 for the faint sample, while the percentage of unknown redshifts is 15 and 13 per cent, respectively. In both cases, the star contamination is lower than 2 per cent. We evaluate how well the ELG redshifts are measured using the target selection photometry and validating with the spectroscopic redshifts measured by eBOSS. We explore different techniques to reduce the photometric redshift outliers fraction with a comparison between the template fitting, the neural networks and the random forest methods. Finally, we study the clustering properties of the DES SVA1 ELG samples. We select only the most secure spectroscopic redshift in the redshift range 0.6 < z < 1.2, leading to a mean redshift for the bright and faint sample of 0.85 and 0.90, respectively. We measure the projected angular correlation function and obtain a galaxy bias averaging on scales from 1 to 10 Mpc h−1 of 1.58 ± 0.10 for the bright sample and 1.65 ± 0.12 for the faint sample. These values are representative of a galaxy population with MB − log(h) < −20.5, in agreement with what we measure by fitting galaxy templates to the photometric data

Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Background After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1.4-1.8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes