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Sökning: WFRF:(Supple D.)

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  • Schofield, James P. R., et al. (författare)
  • Stratification of asthma phenotypes by airway proteomic signatures
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - Elsevier. - 0091-6749 .- 1097-6825. ; 144:1, s. 70-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.
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  • Liuba, Ioan, et al. (författare)
  • Scar progression in patients with nonischemic cardiomyopathy and ventricular arrhythmias
  • 2014
  • Ingår i: Heart Rhythm. - Elsevier. - 1547-5271. ; 11:5, s. 755-762
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Disease progression in patients with nonischemic cardiomyopathy (NICM) is poorly understood. OBJECTIVE To assess left ventricular(LV) scar progression and dilatation by using endocardial electroanatomic mapping. METHODS We studied 13 patients with NICM and recurrent ventricular tachycardia. Two detailed sinus rhythm endocardial voltage maps(265 +/- 122 points/map) were obtained after a mean of 32 months(range 9-77 months). The scar area, defined by low bipolar (BI; less than 1.5 mV) and unipolar(UNI; less than 8.3 mV) endocardial voltage, and the LV volume were measured and compared. A scar difference of greater than 6% of the LV surface and an increase in LV volume of greater than= 20 mL were considered beyond measurement error. RESULTS Six (46%) patients had an increase in scar area beyond boundaries of prior ablation. Five patients had an increase in UNI and 1 patient had an increase in both BI and UNI areas. The increase in BI area represented 16% and the increase in UNI area represented 6.5%-46.2% of the LV surface. A significant decrease in LV ejection fraction was found only in patients with scar progression (from 39% +/- 8%:p = .0003) (LV volume increase ranging between 9% and 23%) was noted in 3 patients, all of whom had scar progression. CONCLUSIONS Progressive scarring with an increase in the area of UNI and less commonly BI electrogram abnormality is seen in 46% of the patients with NICM and ventricular tachycardia and is associated with LV dilatation and decrease in LV ejection fraction. The prominent UNI abnormality suggests predominantly midmyo-cardial or epicardial scarring.
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