Aims
Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non‐invasive means of quantifying volume status exists. Because weight and haematocrit are related to PV, they can be used to calculate relative PV status (PVS). We tested the validity and prognostic utility of calculated PVS in CHF patients.
Methods and results
First, we evaluated the agreement between calculated actual PV (aPV) and aPV levels measured using 125Iodine‐human serum albumin. Second, we derived PVS as: [(calculated aPV – ideal PV)/ideal PV] × 100%. Third, we assessed the prognostic implications of PVS in 5002 patients from the Valsartan in Heart Failure Trial (Val‐HeFT), and validated this in another 246 routine CHF outpatients. On analysis, calculated and measured aPV values correlated significantly in 119 normal subjects and 30 CHF patients. In the Val‐HeFT cohort, mean (+SD) PVS was –9 ± 8% and related to volume biomarkers such as brain natriuretic peptide (BNP). Over 2 years, 977 (20%) patients died. Plasma volume status was associated with death and first morbid events in a ‘J‐shaped’ fashion with the highest risk seen with a PVS > –4%. Stratification into PVS quartiles confirmed that a PVS > –4% was associated with increased mortality (unadjusted hazard ratio 1.65, 95% confidence interval 1.44–1.88, χ2 = 54, P < 0.001) even after adjusting for 22 variables, including brain natriuretic peptide. These results were mirrored in the validation cohort.
Conclusions
Relative PVS calculated from simple clinical indices reflects the degree to which patients have deviated from their ideal PV and independently relates to outcomes. The utility of PVS‐driven CHF management needs further evaluation.
Mitogen-activated protein kinase (MPK) cascades are important for eukaryotic signal transduction. They convert extracellular stimuli (e.g. some hormones, growth factors, cytokines, microbe- or damage-associated molecular patterns) into intracellular responses while at the same time amplifying the transmitting signal. By doing so, they ensure proper performance, and eventually survival, of a given organism, for example in times of stress. MPK cascades function via reversible phosphorylation of cascade components MEKKs, MEKs, and MPKs. In plants the identity of most MPK substrates remained elusive until now. Here, we provide a robust and powerful approach to identify and quantify, with high selectivity, site-specific phosphorylation of MPK substrate candidates in the model plant Arabidopsis thaliana. Our approach represents a two-step chromatography combining phosphoprotein enrichment using Al(OH)3-based metal oxide affinity chromatography, tryptic digest of enriched phosphoproteins, and TiO2-based metal oxide affinity chromatography to enrich phosphopeptides from complex protein samples. When applied to transgenic conditional gain-of-function Arabidopsis plants supporting in planta activation of MPKs, the approach allows direct measurement and quantification ex vivo of site-specific phosphorylation of several reported and many yet unknown putative MPK substrates in just a single experiment.
Glucagon infusion in refractory anaphylactic shock in patients on beta-blockers Report by Martin Thomas, Specialist Registrar Checked by Ian Crawford, Senior Clinical Fellow
BackgroundAspecific scoring systems are used to predict the risk of death postsurgery in patients with infective endocarditis (IE). The purpose of the present study was both to analyze the risk factors for in‐hospital death, which complicates surgery for IE, and to create a mortality risk score based on the results of this analysis.Methods and ResultsOutcomes of 361 consecutive patients (mean age, 59.1±15.4 years) who had undergone surgery for IE in 8 European centers of cardiac surgery were recorded prospectively, and a risk factor analysis (multivariable logistic regression) for in‐hospital death was performed. The discriminatory power of a new predictive scoring system was assessed with the receiver operating characteristic curve analysis. Score validation procedures were carried out. Fifty‐six (15.5%) patients died postsurgery. BMI >27 kg/m2 (odds ratio [OR], 1.79; P=0.049), estimated glomerular filtration rate <50 mL/min (OR, 3.52; P<0.0001), New York Heart Association class IV (OR, 2.11; P=0.024), systolic pulmonary artery pressure >55 mm Hg (OR, 1.78; P=0.032), and critical state (OR, 2.37; P=0.017) were independent predictors of in‐hospital death. A scoring system was devised to predict in‐hospital death postsurgery for IE (area under the receiver operating characteristic curve, 0.780; 95% CI, 0.734–0.822). The score performed better than 5 of 6 scoring systems for in‐hospital death after cardiac surgery that were considered.ConclusionsA simple scoring system based on risk factors for in‐hospital death was specifically created to predict mortality risk postsurgery in patients with IE.
Background: Current epidemiological evidence suggests that the prevalence of preserved systolic function in patients with heart failure varies widely from 13 to 74%. This inconsistency suggests a lack of consensus as to what this condition really is and how it has been characterised for epidemiological studies. Aims: In this review, we summarise and discuss the current understanding of the epidemiology of heart failure with preserved systolic function and the challenges that this raises. Methods: Studies were identified from Medline and Embase Literature Database searches using the subject headings heart failure, diastolic heart failure, epidemiology, incidence, prevalence, diagnosis, prognosis and mortality. Results: Sixty-one studies of congestive heart failure with preserved systolic function were reviewed. There is great diversity in the criteria used to determine whether heart failure is present, the patient population, the setting of the study and methods of evaluating left ventricular function. This makes epidemiological studies of prevalence, morbidity and mortality impossible to compare. Conclusions: The diagnosis of this syndrome might be better defined in terms of symptoms, elevated neuro hormones and impaired cardiac workload. This would allow accurate identification of cases so that further research could be conducted to measure outcome and assess therapeutic benefit.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.