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BACKGROUND The clinical course of patients with moderate aortic stenosis (AS) remains incompletely defined.OBJECTIVES This study sought to analyze the clinical course of moderate AS and compare it with other stages of the disease.METHODS Multiple electronic databases were searched to identify studies on adult moderate AS. Random-effects models were used to derive pooled estimates. The primary endpoint was all-cause death. The secondary endpoints were cardiac death, heart failure, sudden death, and aortic valve replacement.RESULTS Among a total of 25 studies (12,143 moderate AS patients, 3.7 years of follow-up), pooled rates per 100 person-years were 9.0 (95% CI: 6.9 to 11.7) for all-cause death, 4.9 (95% CI: 3.1 to 7.5) for cardiac death, 3.9 (95% CI: 1.9 to 8.2) for heart failure, 1.1 (95% CI: 0.8 to 1.5) for sudden death, and 7.2 (95% CI: 4.3 to 12.2) for aortic valve replacement. Meta-regression analyses detected that diabetes (P = 0.019), coronary artery disease (P = 0.017), presence of symptoms (P < 0.001), and left ventricle (LV) dysfunction (P = 0.009) were associated with a significant impact on the overall estimate of all-cause death. All-cause mortality was higher in patients with reduced LV ejection fraction (

Background: APECED syndrome is a rare monogenic disease caused by homozygous mutation of AIRE gene. It classically presents with chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency with an early onset in childhood. Non-endocrine manifestations as ectodermic dystrophy, asplenism and pneumonitis are also observed but their incidence remains unknown and their mechanisms not well understood. APECED has been poorly reported in France although it is widely described in several European countries. The aim of this study was to report on rare manifestations of APECED syndrome in a French cohort. Patients and methods: We performed a multicentric prospective observational study in France in order to collect clinical, biological, immunological and genetic data, after written informed consent in the frame of a PHRC (Hospital Project of Clinical Research #1927). Bronchiolitis, splenic atrophy and ocular manifestations were systematically investigated. Results We enrolled 25 patients between 2009 and 2016. Clinically, the median age at diagnosis was 12 while the median age of the first manifestation was 6, so there was diagnostic delay. The median number of manifestations was seven. 76 % of patients presented with the classical triad. Reduction of lung function was observed in 62% of patients, asplenism in 26%, and ocular manifestation in 33%. Genetically, eleven mutations of the AIRE gene were identified, two of which never previously reported: an intronic variation c.653-70G>A (intron 5) in a patient with hypoparathyroidism as unique manifestation , and c.1066del (p.Arg356GlyfsX22) (exon 9) in a patient from Guadeloupe with composite heterozygous mutations (c.967_979del13; exon 8). The most common AIRE mutation was the mutation R257X. Median age was 26 and sex ratio was 1.1. Biologically, 100% of tested sera were positive for anti-IFNα-antibodies, 15/18 for anti-IL-22, and 13/18 for anti-IL-17F antibodies. Conclusion: This series shows a high genotypic and phenotypic variability of APECED in France, that could be explained by different ethnic origins. The systematic screening for non-classic manifestations shows a more frequent occurrence than in other series. Systematic screening of asplenism and bronchiolitis could be a useful strategy to make an earlier diagnosis, to prevent infections by vaccination and to treat earlier pulmonary involvement. Lastly, antibodies against Th17 cytokines appear as good soluble markers for diagnosis of non-classical presentation of the syndrome.

Heart failure (HF) remains a main cause of mortality worldwide. Risk stratification of patients with systolic chronic HF is critical to identify those who may benefit from advanced HF therapies. The aim of this study is to identify plasmatic proteins that could predict the early death (within 3 years) of HF patients with reduced ejection fraction hospitalized in CHRU de Lille. The subproteome targeted by an aptamer-based technology, the Slow Off-rate Modified Aptamer (SOMA) scan assay of 1310 proteins, was profiled in blood samples from 168 HF patients, and 203 proteins were significantly modulated between patients who died of cardiovascular death and patients who were alive after 3 years of HF evaluation (Wilcoxon test, FDR 5%). A molecular network was built using these 203 proteins, and the resulting network contained 2281 molecules assigned to 34 clusters annotated to biological pathways by Gene Ontology. This network model highlighted extracellular matrix organization as the main mechanism involved in early death in HF patients. In parallel, an adaptive Least Absolute Shrinkage and Selection Operator (LASSO) was performed on these 203 proteins, and six proteins were selected as candidates to predict early death in HF patients: complement C3, cathepsin S and F107B were decreased and MAPK5, MMP1 and MMP7 increased in patients who died of cardiovascular causes compared with patients living 3 years after HF evaluation. This proteomic signature of 6 circulating plasma proteins allows the identification of systolic HF patients with a risk of early death.