Erratum to: New oral anticoagulants in atrial fibrillation: a reappraisal of trial results looking at absolute figures

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A re-appraisal of thrombogenesis in COVID-19, seen as a multiple Complex System

The aim of this essay is to re-consider the peculiar type of thrombogenesis observed in severe cases of COVID-19 infection, focusing on the multiple interconnected networks involved, such as inflammation, blood coagulation, fibrinolysis, and immune responses. These linked mechanisms can be assimilated to the "Complex Systems" (CS), that play a capital role in various domains: from physics to chemistry, biology and medicine, to social and behavioral sciences. CS are characterized by eliciting variable responses: their final results can be contradictory and often unpredictable. In fact, in severe COVID-19 various outcomes can occur, such as macro- and micro-thrombosis, vasculitis, hemorrhage, hyper and hypo fibrinolysis, distorted inflammatory and immune response, and others. The insight supplied by the CS theory in understanding thrombogenesis in COVID-19 can be useful in several ways. It recalls the importance of a "holistic" view of multiple patterns of signs, symptoms and biomarkers; stresses the added value of global versus mechanistic tests, particularly in coagulation and fibrinolysis; suggests building up small trials of selected patients in a perspective of precision medicine; discourages passive transfer of therapeutic choices from no- COVID to COVID patients; and finally indicates that some treatments, as the anti-inflammatory and the anti-coagulant ones, should be initiated as early as possible, so to avoid worsening of the condition by repetitive feedback and shortcut mechanisms

aspirin therapy in primary cardiovascular disease prevention a position paper of the european society of cardiology working group on thrombosis

Although the use of oral anticoagulants (vitamin K antagonists) has been abandoned in primary cardiovascular prevention due to lack of a favorable benefit-to-risk ratio, the indications for aspirin use in this setting continue to be a source of major debate, with major international guidelines providing conflicting recommendations. Here, we review the evidence in favor and against aspirin therapy in primary prevention based on the evidence accumulated so far, including recent data linking aspirin with cancer protection. While awaiting the results of several ongoing studies, we argue for a pragmatic approach to using low-dose aspirin in primary cardiovascular prevention and suggest its use in patients at high cardiovascular risk, defined as $2 major cardiovascular events (death, myocardial infarction, or stroke) projected per 100 person-years, who are not at increased risk of bleeding. (J Am Coll Cardiol 2014;64:319–27) © 2014 by the American College of Cardiology Foundation

Use and Misuse of Aspirin in Primary Cardiovascular Prevention

The use of low-dose aspirin in primary prevention of cardiovascular (CV) events in healthy or apparently healthy people is a widely debated topic. Many arguments indicate that “primary prevention” is only a conventional definition and that the transition from primary to secondary prevention represents a continuum of increasing levels of CV risk. Although there are no direct proofs of a different efficacy of aspirin at different CV risk levels, in low-risk populations aspirin will appear to be less efficient. In fact, the lower number of events occurring in patients at low risk yields lower absolute numbers of events prevented. As many as 6 meta-analyses of trials of primary CV prevention with aspirin versus placebo, performed between 2009 and 2016, confirmed the above concepts and showed a concordant, significant reduction in nonfatal myocardial infarction, with no significant effects on stroke, as well as on CV and all-cause mortality. The recent demonstration of a moderate protective effect of aspirin on cancer (especially colorectal) confers, however, additional value to the use of aspirin, although unusually long durations of treatment and optimal daily compliance seem to be necessary. Because aspirin increases the bleeding risk, the evaluation of its net clinical benefit is an important point of debate. Thus, it is justified to search for a cutoff level of global CV risk above which the net clinical benefit of aspirin becomes evident. Such a threshold value has been calculated considering the data of 9 primary prevention trials, by the Thrombosis Group of the European Society of Cardiology, and has been indicated as a risk value of 2 or more major CV events per 100 persons per year. Also, in the recent 2016 US Guidelines, the main criterion adopted for the indication of aspirin is the level of global CV risk (suggested cutoff is 1 or more major CV events per 100 persons per year). Beyond the different values selected, it is seems very important to introduce to clinical practice and future trials a new criterion based on the level of global CV risk

Why include the humanities in medical studies?

The relation between philosophy and biomedicine has been reassessed and rethought in the last few years: on the one hand, philosophy of science has paid increasing attention to actual modes of biomedical research and clinical practice; on the other, classes in philosophy, and more generally, in the humanities, have started entering medical curricula. However, the role of philosophy in medical education is not yet unanimously recognized, with situations differing significantly in various national and international contexts. In line with the tradition in Italy and other countries of reflecting on clinical methodology and with the recent initiatives at the crossroads between medicine and philosophy, this contribution aims to argue for the mutual relevance of medicine and philosophy in educational processes, and to suggest some possible forms of implementation of their interactions

Thrombosis

ulfur-containing amino acid which originates from demethylation of dietary methionine. The metabolism of HCy involves remethylation and transsulfuration pathways. The remethylation pathway requires vitamin B12, as a cofactor of methionine synthase (EC 2.1.1.13), and folates as co-enzymes. The transsulfuration pathway requires vitamin B6 (PLP) as a co-factor for cystathionine #-synthase (EC 4.2.1.22) and cystathionine-#-lyase (EC 4.4.1.1). Genetic disorders and vitamin deficiencies can lead to increased concentrations of HCy in plasma. 1-5 Elevated HCy plasma levels have been independently associated with an increased risk of atherosclerosis and thrombosis 6-8 although a causal role of HCy in cardiovascular disease has not been firmly established yet. 9,10 Fasting total HCy (FtHCy) concentration has been shown to be a function of age, gender and vitamin status in healthy subjects by several authors. 3,11-13 The methionine -load (ML) test is a measure of HCy concentrations afte