Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Give Life a Chance: John Lennon e l'utopia del pacifismo

This essay concentrates on the final years of John Lennon's collaboration with the Beatles, and on the very first years of his solo career when he decides to get into the world struggle for peace and freedom. One of the key texts here analyzed is "Imagine" whose impact is also studied through some of the italian translations and mis- translations by Ornella Vanoni and Gino Paoli

Exome sequencing in HFE C282Y homozygous men with extreme phenotypes identifies a GNPAT variant associated with severe iron overload

To identify polymorphisms associated with variability of iron overload severity in <em>HFE</em>-associated hemochromatosis, we performed exome sequencing of DNA from 35 male <em>HFE</em> C282Y homozygotes with either markedly increased iron stores (n=22; cases) or with normal or mildly increased iron stores (n=13; controls). The 35 participants, residents of the United States, Canada, and Australia, reported no or light alcohol consumption. Sequencing data included 82,068 single-nucleotide variants, and 10,337 genes were tested for a difference between cases and controls. A variant in the <em>GNPAT</em> gene showed the most significant association with severe iron overload (<em>P</em>=3 x10^-6; <em>P</em>=0.033 by the likelihood ratio test after correction for multiple comparisons). Sixteen of twenty-two participants with severe iron overload had <em>glyceronephosphate O-acyltransferase</em> (<em>GNPAT</em>) polymorphism p.D519G (rs11558492; 15 heterozygotes, one homozygote). No control participant had this polymorphism. To examine functional consequences of <em>GNPAT</em> deficiency, we performed small interfering RNA based knockdown of <em>GNPAT</em> in the human liver-derived cell line, HepG2/C3A. This knockdown resulted in a 17-fold decrease in expression of the messenger RNA encoding the iron-regulatory hormone, hepcidin. \ud \ud <em>Conclusion: GNPAT</em> p.D519G is associated with a high-iron phenotype in <em>HFE</em> C282Y homozygotes and may participate in hepcidin regulation. (H<span class="smallCaps">epatology</span> 2015;62:429-43

Lipoprotein (a) and stroke

Strokes are one of the most common causes of mortality and long term severe disability. There is evidence that lipoprotein (a) (Lp(a)) is a predictor of many forms of vascular disease, including premature coronary artery disease. Several studies have also evaluated the association between Lp(a) and ischaemic (thrombotic) stroke. Several cross sectional (and a few prospective) studies provide contradictory findings regarding Lp(a) as a predictor of ischaemic stroke. Several factors might contribute to the existing confusion—for example, small sample sizes, different ethnic groups, the influence of oestrogens in women participating in the studies, plasma storage before Lp(a) determination, statistical errors, and selection bias. This review focuses on the Lp(a) related mechanisms that might contribute to the pathogenesis of ischaemic stroke. The association between Lp(a) and other cardiovascular risk factors is discussed. Therapeutic interventions that can lower the circulating concentrations of Lp(a) and thus possibly reduce the risk of stroke are also considered. Key Words: atherothrombosis • fibrinogen • homocysteine • lipids • lipoprotein a • strok