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Background Lack of standardization of outcome measures limits the usefulness of clinical trial evidence to inform health care decisions. This can be addressed by agreeing on a minimum core set of outcome measures per health condition, containing measures relevant to patients and decision makers. Since 1992, the Outcome Measures in Rheumatology (OMERACT) consensus initiative has successfully developed core sets for many rheumatologic conditions, actively involving patients since 2002. Its expanding scope required an explicit formulation of its underlying conceptual framework and process. Methods Literature searches and iterative consensus process (surveys and group meetings) of stakeholders including patients, health professionals, and methodologists within and outside rheumatology. Results To comprehensively sample patient-centered and intervention-specific outcomes, a framework emerged that comprises three core "Areas," namely Death, Life Impact, and Pathophysiological Manifestations; and one strongly recommended Resource Use. Through literature review and consensus process, core set development for any specific health condition starts by identifying at least one core "Domain" within each of the Areas to formulate the "Core Domain Set." Next, at least one applicable measurement instrument for each core Domain is identified to formulate a "Core Outcome Measurement Set." Each instrument must prove to be truthful (valid), discriminative, and feasible. In 2012, 96% of the voting participants (n = 125) at the OMERACT 11 consensus conference endorsed this model and process. Conclusion The OMERACT Filter 2.0 explicitly describes a comprehensive conceptual framework and a recommended process to develop core outcome measurement sets for rheumatology likely to be useful as a template in other areas of health care. © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Objectives: Parathyroid hormone (PTH) is a major systemic calcium-regulating hormone. Recent evidence has suggested that measurement of PTH might provide complementary information for the diagnosis and risk stratification of patients with heart failure (HF). The aim of our study was to compare intact and bioactive PTH assays in patients with severe heart failure. Design and methods: The following measurements were carried out in blood samples from 73 patients with severe heart failure: bioactive PTH (1-84) assay, intact PTH assay, non-PTH (1-84), 25-hydroxyvitamin D, B-type natriuretic peptide (BNP), N-terminal proBNP (Nt-proBNP), Galectin-3 and high sensitive troponin T (hsTnT). Results: The correlation between intact and bioactive PTH assays was very high in HF patients. However, the bioactive PTH concentrations were lower than those measured with the intact assay. Intact and bioactive PTH as well as non-PTH (1-84) was significantly and positively correlated to BNP, Nt-proBNP, and galectin-3 but not to hsTnT. The strongest relationships with these cardiac biomarkers and with cardiovascular death were observed with the bioactive PTH assay. Conclusions: The PTH concentrations obtained with intact and bioactive assays are not comparable in patients with severe HF. The specificity of PTH assays might therefore impact on the potential diagnosis and prognosis values of PTH testing in patients with heart failur

Objectives: The aim of our study was to determine NT-proBNP concentrations in heart failure (HF) patients with a luminescent oxygen channeling immunoassay (LOCI®). Design and methods: Seventy HF patients were enrolled. NT-proBNP levels were measured with LOCI® method and compared to a reference NT-proBNP assay. Results: LOCI® NT-proBNP levels were significantly correlated with the reference NT-proBNP assay and were related to HF severity. Conclusions: LOCI® assay demonstrates performances close to the comparative assay for NT-proBNP testing and allows a significant reduction of the time of analysis.

Galectins are carbohydrate binding proteins involved in several biological functions such as intracellular signaling, cell to cell interaction and exchanges between cells and the extracellular matrix. Galectins are therefore participating to the control of gene expression, the regulation of immune response and the control of cell growth and viability. Galectins have stimulated in one hand a great interest for their potent contribution to the physiopathology of several diseases and cancers and may represent in another hand relevant biomarkers to support the diagnosis and prognosis of several disorders.

Age-related changes of gene expression contribute to the physiological alteration observed with human ageing. Herein the abundance of a selection of 148 transcripts involved in immunosenescence and stress response was compared in total RNA of PBMC of healthy young to middle-age probands (35.0 +/- 6.5 year old) and healthy old probands (82.5 +/- 6.8 year old). This study provides a list of 16 differentially abundant transcripts species in the healthy old probands. Thus these changes of abundance can be considered as easily accessible biomarkers of ageing. Some of these differential abundances like CD28, CD69, LCK (decreased abundance in old subjects), CD86, cathepsin D, H and S (increased abundance in old subjects) might explain biochemical and cytochemical changes observed at the protein level in the immune system and thus might correspond to regulatory processes affecting the ageing process. Indeed these changes reflect the low-grade proinflammatory status observed in old persons and suggest a hypo-responsiveness of T-cells together with an increase in antigen presentation potential. In addition, among the differentially abundant transcripts were transcripts involved in the oxidative stress response HMOX1 and HSPA6 mRNAs were found as more abundant in PBMC from elderly subjects.

Biomarkers indicating biological age are of significant interest for prevention, diagnosis and monitoring (and the treatment) of age-related diseases. We previously reported an alteration of serum N-glycan profile in old humans using "DNA Sequencer Adapted-Fluorophore Assisted Carbohydrate Electrophoresis" (DSA-FACE). To validate the shift in serum N-glycan profile during ageing, we studied serum N-glycan profiles in different age groups of healthy volunteers, patients with dementia, and patients with Cockayne syndrome, a genetic DNA repair disorder involving neurodegeneration and premature ageing. We found that the log of the ratio of two glycans (NGA2F and NA2F), named GlycoAgeTest, remained steady up to the age of 40years and thereafter gradually increased to reach its highest level in nonagenarians. Patients with dementia or Cockayne syndrome had a higher GlycoAgeTest level than age-matched healthy individuals. We thus demonstrate that the value of GlycoAgeTest is better than chronological age for estimating the physiological age of a human individual, and that it could be used as an ageing biomarker for healthy humans. Our data indicate that the GlycoAgeTest could be used as a non-invasive surrogate marker for general health, for forecasting disease progression during ageing, and for monitoring the efficacy of anti-ageing food compounds.

Cadmium ( Cd) exposure results in injury to the proximal tubule characterized by polyuria and proteinuria. Kidney injury molecule-1 ( Kim-1) is a transmembrane glycoprotein not normally detected in the mature kidney, but is upregulated and shed into the urine following nephrotoxic injury. In this study, we determine if Kim-1 might be a useful early biomarker of Cd nephrotoxicity. Male Sprague-Dawley rats were given daily injections of Cd for up to 12 weeks. Weekly urine samples were analyzed for Kim-1, protein, creatinine, metallothionein, and Clara cell protein CC-16. Significant levels of Kim-1 were detected in the urine by 6 weeks and continued to increase throughout the treatment period. This appearance of Kim-1 occurred 4-5 weeks before the onset of proteinuria, and 1-3 weeks before the appearance of metallothionein and CC-16. Higher doses of Cd gave rise to higher Kim-1 excretion. Reverse transcriptase-polymerase chain reaction ( RT-PCR) expression analysis showed that Kim-1 transcript levels were increased after 6 weeks at the low dose of Cd. Immunohistochemical analysis showed that Kim-1 was present in proximal tubule cells of the Cd-treated rats. Our results suggest that Kim-1 may be a useful biomarker of early stages of Cd-induced proximal tubule injury.

type:Text, Background: Pentosidine, one of the advanced glycation end products (AGE), is generated by nonenzymatic glycation and oxidation of proteins. The receptor of AGE (RAGE) is expressed in a variety of tissue, and interaction of AGE with RAGE induces oxidative stress and activation of intracellular signaling causing production of cytokines and mediators of inflammation. We investigated whether serum pentosidine is a risk factor for heart failure. Methods: Serum pentosidine concentration was measured in 141 patients with heart failure and 18 control subjects by a competitive enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 479 days with endpoints of cardiac death or re-hospitalization. Results: Serum concentration of pentosidine was significantly higher in NYHA class III/IV patients than in NYHA class I/II patients (P < 0.0001). Serum pentosidine was also higher in patients with cardiac events than in event free patients (P < 0.001). In the univariate Cox proportional hazard analysis, age, NYHA class, pentosidine, creatinine, uric acid, B-type natriuretic peptide, left ventricular end-systolic volume and left ventricular mass were significant risk factors to predict cardiac events. In the multivariate Cox analysis, serum pentosidine concentration was an independent risk factor for cardiac events (hazard ratio 1.88, 95% confidence interval 1.23 . 2.69, P = 0.002). Patients were divided into 4 groups based on the serum pentosidine levels. The highest 4th quartile of pentosidine was associated with the highest risk of cardiac events (4.52-fold). Conclusions: Serum pentosidine concentration is an independent prognostic factor for heart failure, and this new marker may be useful for risk stratification of patients with heart failure.

Genes that are expressed in adult muscle, but not in myotubes, are useful markers of the last steps of muscle maturation. We have investigated at what stage of differentiation the muscle-specific (M) promoter of a gene that codes for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2) becomes functional. M-PFK2 mRNA, which is present in adult muscle, did not appear during differentiation of L6 myoblasts into myotubes induced by growth factor withdrawal and hormonal treatment, even when this differentiation was stimulated by expression of transgenes coding for myf-5 or Rb. A comparison with the expression pattern of muscle genes showed that M-PFK2 is a marker of mature skeletal muscle. We also found that M-PFK2 is expressed in both types (slow-twitch and fast-twitch) of adult muscle. Thus, the M-PFK2 promoter is a novel model for studying the transcriptional control of the final steps of muscle differentiation that are common to the two types of myofibers.