Explore the vast range of titles available.

The Presage ® ST2 Assay (Critical Diagnostics, CA, USA) is an in vitro diagnostic device that quantitatively measures soluble suppression of tumorigenicity 2 (sST2) in serum and plasma by ELISA. This assay is US FDA approved and is indicated to be used in conjunction with clinical evaluation as an aid in assessing the prognosis of patients diagnosed with chronic heart failure. sST2 binds to IL-33 and functions as a 'decoy' receptor for IL-33, thereby attenuating the systemic effects of IL-33. Due to the role of IL-33/transmembrane isoform of suppression of tumorigenicity 2 signaling in cardiac remodeling, sST2 has emerged as a novel cardiovascular biomarker. In recent studies, it was shown that sST2 is a valuable predictor of several end points in heart failure, in acute coronary syndromes and in critically ill patients. In this review, analytical considerations and clinical applications of the Presage ST2 Assay will be discussed, as well as probable future concepts for adoption of sST2 measurements into clinical practice.

Background Administration of lipopolysaccharide (LPS) from Gram-negative bacteria, also known as the human endotoxemia model, is a standardized and safe model of human inflammation. Experimental studies have revealed that peripheral administration of LPS leads to induction of the kynurenine pathway followed by depressive-like behavior and cognitive dysfunction in animals. The aim of the present study is to investigate how acute intravenous LPS administration affects the kynurenine pathway in healthy male human subjects. Methods The present study is a prospective, single-blinded, randomized, placebo-controlled cross-over study to investigate the effects of intravenously administered LPS (Escherichia coli O113, 2 ng/kg) on tryptophan and kynurenine metabolites over 48 h and their association with interleukin-6 (IL-6) and C-reactive protein (CRP). The study included 10 healthy, non-smoking men (18–40 years) free from medication. Statistical differences in tryptophan and kynurenine metabolites as well as associations with IL-6 and CRP in LPS and placebo treated subjects were assessed with linear mixed-effects models. Results Systemic injection of LPS was associated with significantly lower concentrations of plasma tryptophan and kynurenine after 4 h, as well as higher concentrations of quinolinic acid (QUIN) after 48 h compared to the placebo injection. No differences were found in kynurenic acid (KYNA) or picolinic acid plasma concentrations between LPS or placebo treatment. The KYNA/kynurenine ratio peaked at 6 h post LPS injection while QUIN/kynurenine maintained significantly higher from 3 h post LPS injection until 24 h. The kynurenine/tryptophan ratio was higher at 24 h and 48 h post LPS treatment. Finally, we report an association between the kynurenine/tryptophan ratio and CRP. Conclusions Our findings strongly support the concept that an inflammatory challenge with LPS induces the kynurenine pathway in humans, activating both the neurotoxic (QUIN) and neuroprotective (KYNA) branch of the kynurenine pathway. Trial registration This study is based on a study registered at ClinicalTrials.gov, NCT03392701 . Registered 21 December 2017.

Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from ventricular cardiomyocytes. The pathophysiological mechanisms linking heart failure and appetite regulation remain unknown. In this study, we investigated the impact of intravenous BNP administration on appetite-regulating hormones and subjective ratings of hunger and satiety in 10 healthy volunteers. Participants received in a randomized, placebo-controlled, crossover, single-blinded study (subject) placebo once and 3.0 pmol/kg/min human BNP-32 once administered as a continuous infusion during 4 h. Circulating concentrations of appetite-regulating peptides were measured hourly. Subjective ratings of hunger and satiety were evaluated by visual analog scales. BNP inhibited the fasting-induced increase in total and acylated ghrelin concentrations over time (P = 0.043 and P = 0.038, respectively). In addition, BNP decreased the subjective rating of hunger (P = 0.009) and increased the feeling of satiety (P = 0.012) when compared with placebo. There were no significant changes in circulating peptide YY, glucagon-like peptide 1, oxyntomodulin, pancreatic polypeptide, leptin, and adiponectin concentrations. In summary, our results demonstrate that BNP exerts anorectic effects and reduces ghrelin concentrations in men. These data, taken together with the known cardiovascular properties of ghrelin, support the existence of a heart-gut-brain axis, which could be therapeutically targeted in patients with heart failure and obesity.

Background/Objectives: The COVID-19 pandemic significantly threatened cancer patients and oncologic care. The rollout of vaccines emerged as a critical milestone, despite the initial lack of evidence regarding their safety and efficacy in this population. This systematic review and meta-analysis evaluate the current evidence on COVID-19 vaccination in patients undergoing radiotherapy (RT). Methods: PubMed, Livivo, Scopus, and Cochrane Library were systematically reviewed for relevant publications on COVID-19 vaccination in the context of radiation oncology, published by 19 April 2024. The treatment effects were calculated as the proportion of seroconverted individuals. Results: A total of 22 studies published between 2021 and 2024 were included, covering various aspects of vaccination, including safety, tolerability, qualitative and quantitative humoral responses, cellular responses, vaccination efficacy, and booster vaccinations. Notably, patients undergoing RT exhibited a high willingness to receive vaccination. Vaccination was overall well tolerated and safe, with a low incidence of side effects, which were primarily mild. The primary meta-analysis showed a seroconversion proportion of 91% [95% CI: 84–96%] overall, with a somewhat higher proportion of 93% in patients receiving RT alone, compared to 90% in patients receiving either RT or RT combined with chemotherapy. Furthermore, immunization during RT led to a sustained increase in antibody titers, with a notable long-term persistence of IgG. Conclusions: COVID-19 vaccines demonstrate excellent safety, immunogenicity, and efficacy in patients receiving RT, who also exhibit a high willingness to be vaccinated. The outcomes observed are comparable to those in healthy controls and superior to those seen in patients receiving other cancer treatments, such as chemotherapy. The vaccination of radiation oncology patients in future pandemics or epidemics is strongly advocated even during active treatment.

A-type natriuretic peptide (ANP) and adrenomedullin (ADM) are potent hypotensive, diuretic, and natriuretic peptides involved in maintaining cardiovascular and renal homeostasis. We conducted a prospective 7-year study of 177 nondiabetic patients with primary chronic kidney disease to see if ANP and ADM plasma concentrations predict the progression of their disease, using novel sandwich immunoassays covering the midregional epitopes of the stable prohormones (MRproANP and MR-proADM). Progression of chronic kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure, which occurred in 65 patients. Analysis of the receiver operating characteristic curve for the prediction of renal endpoints showed similar areas under the curve for the glomerular filtration rate (GFR) (0.838), MR-proANP (0.810), and MRproADM (0.876), respectively, as did the Kaplan–Meier curve analyses of the patients stratified according to the median of the respective markers. In separate multiple Cox-proportional hazard regression analyses, increased plasma concentrations of both peptides were each strongly predictive of the progression of chronic kidney disease after adjustments for age, gender, GFR, proteinuria and amino-terminal pro-B-type natriuretic peptide. Our study suggests that MR-proANP and MR-proADM are useful new markers of progression of primary nondiabetic chronic kidney disease.

Background: Cancer patients are highly prone to infectious diseases. While undergoing antineoplastic treatment, the risk of severe symptoms upon infection increases, necessitating efficient protective measures, such as vaccination. For patients receiving radiotherapy, there is no specific information about humoral immunity. During the COVID-19 pandemic, serial antibody measurements were therefore offered to cancer patients, following SARS-CoV-2 vaccination while obtaining radiotherapy. Methods: Out of 74 enrolled patients, 46 met the inclusion criteria. Two cohorts were allocated, depending on an association with chemotherapy or pure radiotherapy. An additional healthy control cohort of 16 healthcare workers was enrolled. All participants followed a two-fold BNT162b2 vaccine schedule. SARS-CoV-2 binding antibodies were measured serially in a 7-day cycle for 35 days and over the long-term, using the Elecsys® Anti-SARS-CoV-2 immunoassay. Results: Cancer patients under pure radiotherapy have a comparable humoral vaccination response and long-term persistency of antibodies to healthy controls. Patients receiving additional chemotherapy show a significantly delayed immune response and decreased antibody titers. The vaccine was well tolerated in all cohorts. Conclusions: Pure radiotherapy in cancer patients does not interfere with the vaccine-induced humoral immune response or other immunogenetic aspects, whereas previous or simultaneous chemotherapy does. Findings are of particular relevance for future epidemic or pandemic scenarios.

Objective The variability in warfarin dose requirement is attributable to genetic and environmental factors. Acenocoumarol (AC) and phenprocoumon (PC) are coumarin derivates widely prescribed in European countries for the prevention and treatment of thromboembolic events. The aim of our study was to investigate the contribution of genes involved in the vitamin K cycle to AC and PC maintenance doses. Methods Common single nucleotide polymorphisms (SNPs) in the genes encoding cytochrome P450 family member 2C9 ( CYP2C9 ), vitamin K epoxide reductase complex subunit 1 ( VKORC1 ), γ-glutamyl carboxylase ( GGCX ), calumenin ( CALU ) and apolipoprotein E ( APOE ) were studied in 206 patients receiving AC or PC. Results Compared to patients with the VKORC1 C1173C genotype, maintenance doses for AC or PC were reduced to 74.6 or 70.2% in heterozygous C1173T subjects and to 48.6 or 48.1% in homozygous T1173T subjects ( P  < 0.0001). Furthermore maintenance doses for AC and PC were significantly lower in heterozygous CYP2C9*1*3 , CYP2C9*2*3 , and in CYP2C9*3*3 homozygote individuals compared to homozygous CYP2C9*1*1 subjects ( P  = 0.0004 and P  = 0.0017, respectively). A multiple regression model including age, sex, last INR, VKORC1 , and CYP2C9 genotypes explained ~50% of the variability in AC/PC dose requirements. CALU genotype combinations showed minor effects on PC dose requirements. No associations with AC or PC dose requirements were observed for sequence substitutions in the GGCX or APOE genes. Conclusion These results reveal that interindividual variability in weekly AC and PC maintenance dose requirement is mainly dependent on the VKORC1 1173C>T and the CYP2C9*3 alleles. VKORC1 and CYP2C9 genotyping might provide helpful information to prevent serious bleeding events in subjects receiving AC or PC.

Aims Cardiac involvement in myopathies that primarily affect the skeletal muscle is variable and may be subtle, necessitating sensitive diagnostic approaches. Here, we describe the prevalence of cardiac abnormalities in a cohort of patients with skeletal muscle disease presenting at a tertiary care neuromuscular centre. Methods and results We systematically investigated patients with skeletal myopathies and comprehensively analysed their cardiac phenotype including 24 h electrocardiogram, echocardiography with strain analyses, contrast‐enhanced cardiac magnetic resonance imaging, and, if at increased risk of coronary artery disease, computed tomography coronary angiography. We prospectively screened 91 patients with diverse skeletal myopathies and enrolled 73 patients. The most pronounced cardiac involvement was present in patients with dystrophic myopathies (cardiac abnormalities in 59% of patients). We analysed myotonic dystrophies (n = 29) in more detail and found prolonged QRS (99.4 ± 15.6 vs. 91.5 ± 10.3 ms; P = 0.027) and QTc times (441.1 ± 28.1 vs. 413.0 ± 23.3 ms; P < 0.001) and increased left atrial size (27.28 ± 3.9 vs. 25.0 ± 3.2 mm/m2; P = 0.021) when compared with healthy controls. Left ventricular systolic function was reduced (ejection fraction < 55%) in 31% of myotonic dystrophies, while only 4% had an ejection fraction < 50%. Apical peak systolic longitudinal strain was slightly reduced (P = 0.023). Conclusions Screening for cardiac involvement in the skeletal muscle disease seems prudent particularly in patients with dystrophic myopathies. In the subset of myotonic dystrophy patients, QRS and QTc times as well as myocardial strain may be useful parameters. Their potential for predicting cardiac adverse events needs further evaluation.

Early outcome prediction after acute ischemic stroke is of great interest. The aim of our study was to evaluate the prognostic value of blood biomarkers in patients with acute ischemic stroke. We measured interleukin-6 (IL-6), d-dimer, amino-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T, and soluble ST2 plasma concentrations within 24 h after admission to our stroke unit in 721 consecutive acute ischemic stroke patients. End point was 90-day all-cause mortality. During follow-up 81 patients died (11%). In univariate Cox proportional hazards regression analyses with the biochemical markers dichotomized according to median values, all baseline blood biomarkers were strong prognostic markers. However, in the multivariate analysis after adjustment for several clinical variables and the NIH Stroke Scale (NIHSS), only NIHSS >3 [risk ratio (RR) 7.87, 95% CI, 3.61-17.16; < 0.001], IL-6 > 7 pg/mL (RR 4.09, 95% CI, 2.02-8.29; < 0.001), and NT-proBNP >447 ng/L (RR 4.88, 95% CI, 2.41-9.88; < 0.001) remained independent predictors. Using a simple multimarker approach combining these 3 complementary markers, we demonstrated that patients with increased NIHSS, IL-6, and NT-proBNP had the poorest outcome with a mortality rate of 38%, whereas no patient with negative readings for all 3 markers died during follow-up. In this large cohort of patients with acute ischemic stroke, IL-6 and NT-proBNP at admission were strong and independent prognostic markers for 90-day all-cause mortality, and provided complementary prognostic information to the routinely used stroke severity score NIHSS.

According to a proposed concept of a gastrointestinal–renal natriuretic signaling axis, natriuretic peptides are released from the intestine into the circulation in response to oral salt intake and act on the kidneys as hormones to increase sodium excretion. The peptides guanylin and uroguanylin and their precursors proguanylin and prouroguanylin, respectively, have been suggested to be the mediators of this axis. A study by Preston and co-workers, however, provides important data not supporting this putative concept.