Decorin and TGF-β(1 )polymorphisms and development of COPD in a general population

BACKGROUND: Decorin, an extracellular matrix (ECM) proteoglycan, and TGF-β(1 )are both involved in lung ECM turnover. Decorin and TGF-β(1 )expression are decreased respectively increased in COPD lung tissue. Interestingly, they act as each other's feedback regulator. We investigated whether single nucleotide polymorphisms (SNPs) in decorin and TGF-β(1 )underlie accelerated decline in FEV(1 )and development of COPD in the general population. METHODS: We genotyped 1390 subjects from the Vlagtwedde/Vlaardingen cohort. Lung function was measured every 3 years for a period of 25 years. We tested whether five SNPs in decorin (3'UTR and four intron SNPs) and three SNPs in TGF-β(1 )(3'UTR rs6957, C-509T rs1800469 and Leu10Pro rs1982073), and their haplotypes, were associated with COPD (last survey GOLD stage = II). Linear mixed effects models were used to analyze genotype associations with FEV(1 )decline. RESULTS: We found a significantly higher prevalence of carriers of the minor allele of the TGF-β(1 )rs6957 SNP (p = 0.001) in subjects with COPD. Additionally, we found a significantly lower prevalence of the haplotype with the major allele of rs6957 and minor alleles for rs1800469 and rs1982073 SNPs in TGF-β(1 )in subjects with COPD (p = 0.030), indicating that this association is due to the rs6957 SNP. TGF-β(1 )SNPs were not associated with FEV(1 )decline. SNPs in decorin, and haplotypes constructed of both TGF-β(1 )and decorin SNPs were not associated with development of COPD or with FEV(1 )decline. CONCLUSION: Our study shows for the first time that SNPs in decorin on its own or in interaction with SNPs in TGF-β(1 )do not underlie the disturbed balance in expression between these genes in COPD. TGF-β(1 )SNPs are associated with COPD, yet not with accelerated FEV(1 )decline in the general population

ICAR: endoscopic skull‐base surgery

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Acute Decompensated Aortic Stenosis: State of the Art Review.

Aortic stenosis (AS) is a progressive disease that carries a poor prognosis. Patients are managed conservatively until satisfying an indication for transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) based on AS severity and the presence of symptoms or adverse impact on the myocardium. Up to 1 in 3 TAVIs are performed for patients with acute symptoms of dyspnea at rest, angina, and/or syncope - termed acute decompensated aortic stenosis (ADAS) and require urgent aortic valve replacement. These patients have longer hospital length of stay, undergo physical deconditioning, and have a higher rate of acute kidney injury and mortality compared to stable patients with less severe symptoms. There is an urgent need to prevent ADAS and to deliver pathways to manage and improve ADAS-related outcomes. We provide here a contemporary review on epidemiological and pathophysiological aspects of ADAS, with a focus on the impact of ADAS from clinical and economic perspectives. We offer a global overview of the available evidence for treatment of ADAS and with priorities suggested for addressing current gaps in the literature and unmet clinical needs to improve outcomes for AS patients