Journal of internal medicine
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Immunogenicity to tumour necrosis factor inhibitors is a significant clinical problem leading to treatment failure and adverse events. The study aimed to assess human leukocyte antigen (HLA) associations with anti-drug antibody (ADAb) formation to infliximab. ⋯ A genome-wide significant association between two HLA-DQ2 haplotypes and the risk of ADAb formation to infliximab was identified, suggesting that HLA-DQ2 testing may facilitate personalised treatment decisions.
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Sodium-glucose transport inhibitors (SGLT2i) are effective in heart failure (HF) with ejection fraction (EF) <40% (referred to as HF with reduced EF - HFrEF) and left ventricular EF (LVEF) >40%. Current evidence suggests that SGLT2i should be initiated across a large spectrum of EFs and renal function in patients with HF and with and without diabetes. We reviewed the benefits of SGLT2i in the entire spectrum of HF and provided some clues that may guide physicians in their strategy of initiating and maintaining SGLT2i (with or without SGLT1i effect) therapy. ⋯ SGLT2i appear to be effective and well-tolerated drugs in the majority of clinical HF scenarios, regardless of LVEF, estimated glomerular filtration rate, diabetic status or the level of the acuteness of the clinical setting. Therefore, most patients with HF should be treated with SGLT2i. However, in the face of the therapeutic inertia that has been observed in HF over the past decades, the actual implementation of SGLT2i in routine practice remains the most significant challenge.
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Emerging research suggests that exposures occurring years before conception are important determinants of the health of future offspring and subsequent generations. Environmental exposures of both the father and mother, or exposure to disease processes such as obesity or infections, may influence germline cells and thereby cause a cascade of health outcomes in multiple subsequent generations. There is now increasing evidence that respiratory health is influenced by parental exposures that occur long before conception. ⋯ The results are strengthened by mechanistic research from animal models and (scarce) human studies that have identified molecular mechanisms that can explain the epidemiological findings, suggesting transfer of epigenetic signals through germline cells, with susceptibility windows in utero (both male and female line) and prepuberty (male line). The concept that our lifestyles and behaviours may influence the health of our future children represents a new paradigm. This raises concerns for future health in decades to come with respect to harmful exposures but may also open for radical rethinking of preventive strategies that may improve health in multiple generations, reverse the imprint of our parents and forefathers, and underpin strategies that can break the vicious circle of propagation of health inequalities across generations.
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Studies have demonstrated that reducing farnesoid X receptor activity with ursodeoxycholic acid (UDCA) downregulates angiotensin-converting enzyme in human lung, intestinal and cholangiocytes organoids in vitro, in human lungs and livers perfused ex situ, reducing internalization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell. This offers a potential novel target against coronavirus disease 2019 (COVID-19). The objective of our study was to compare the association between UDCA exposure and SARS-CoV-2 infection, as well as varying severities of COVID-19, in a large national cohort of participants with cirrhosis. ⋯ In participants with cirrhosis, UDCA exposure was associated with both a decrease in SARS-CoV-2 infection, and reduction in symptomatic, at least moderate, and severe/critical COVID-19.
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A Mediterranean lifestyle may prevent and mitigate cardiometabolic disorders. We explored whether adherence to a Mediterranean lifestyle was prospectively associated with the risk of metabolic syndrome (MetS) among coronary heart disease (CHD) patients. ⋯ Our results showed that greater adherence to a MEDLIFE reduced the risk of subsequent MetS development and increased the likelihood of reversing preexisting MetS among patients with CHD at baseline.