Journal of internal medicine
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Epigenome-wide association studies (EWAS) identify genes that are dysregulated by the studied clinical endpoints, thereby indicating potential new diagnostic biomarkers, drug targets and therapy options. Combining EWAS with deep molecular phenotyping, such as approaches enabled by metabolomics and proteomics, allows further probing of the underlying disease-associated pathways. For instance, methylation of the TXNIP gene is associated robustly with prevalent type 2 diabetes and further with metabolites that are short-term markers of glycaemic control. ⋯ This knowledge, if carefully interpreted, may indicate novel therapy options and, together with monitoring of the methylation state of specific methylation sites, may in the future allow the early diagnosis of impending disease. It is essential for medical practitioners to recognize the potential that this field holds in translating basic research findings to clinical practice. In this review, we present recent advances in the field of EWAS with metabolomics and proteomics and discuss both the potential and the challenges of translating epigenetic associations, with deep molecular phenotypes, to biomedical applications.
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The pathophysiological mechanisms linking tricuspid regurgitation (TR) and chronic kidney disease (CKD) remain unknown. This study aimed to determine which pathophysiological mechanisms related to TR are independently associated with renal dysfunction and to evaluate the impact of renal impairment on long-term prognosis in patients with significant (≥ moderate) secondary TR. ⋯ Of the pathophysiological mechanisms identified by echocardiography that are associated with significant secondary TR, only severe RV dysfunction was independently associated with the presence of significant renal impairment. In addition, worse renal function according to CKD group was associated with a significant reduction in survival.
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Assessment of the causative association between the COVID-19 and cause of death has been hampered by limited availability of systematically performed autopsies. We aimed to present autopsy-confirmed causes of death in patients who died with COVID-19 and to assess the association between thrombosis and diffuse alveolar damage consistent with COVID-19 (DAD). ⋯ Vast majority of all PCR-positive fatalities, including out-of-hospital deaths, during the SARS-CoV-2 pandemic were related to DAD caused by COVID-19. Pulmonary artery thrombosis and microangiopathy in pulmonary tissue were common and associated with the presence of DAD, whilst venous PE was rarely observed. Histology-confirmed lymphocyte myocarditis was a rare finding.
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Observational Study
Remnant cholesterol predicts progression of diabetic nephropathy and retinopathy in type 1 diabetes.
We aimed to assess whether remnant cholesterol concentration and variability predict the progression of diabetic nephropathy (DN) and severe diabetic retinopathy (SDR) in type 1 diabetes. ⋯ Remnant cholesterol concentration, but not variability, predicts DN progression and development of SDR. However, it remains to be elucidated whether the associations are causal or not.
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Prognostic markers for disease severity and identification of therapeutic targets in COVID-19 are urgently needed. We have studied innate and adaptive immunity on protein and transcriptomic level in COVID-19 patients with different disease severity at admission and longitudinally during hospitalization. ⋯ Critical COVID-19 seems to be characterized by an immune profile of activated and exhausted T cells and monocytes. This immune phenotype may influence the capacity to mount an efficient T-cell immune response. Plasma B-cell activity and calprotectin were higher in critical COVID-19 while most transcripts related to immune functions were reduced, in particular affecting B cells. The potential of these cells as therapeutic targets in COVID-19 should be further explored.