COVID-19: The crucial role of blood coagulation and fibrinolysis.

The overflow of studies in the recent literature on COVID-19 often gives provisional or contradictory results and therefore deserves pauses of reflection and reconsideration. In fact, knowledges of pathophysiology of this new disease are still in development and hence originate discussions and interpretations. Regarding the role of blood coagulation and fibrinolysis, these mechanisms should be considered as crucial especially in severe cases.

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.

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.

Error, contradiction and reversal in science and medicine.

Error and contradictions are not "per se" detrimental in science and medicine. Going back to the history of philosophy, Sir Francis Bacon stated that "truth emerges more readily from error than from confusion", and recently Popper introduced the concept of an approximate temporary truth that constitutes the engine of scientific progress. In biomedical research and in clinical practice we assisted during the last decades to many overturnings or reversals of concepts and practices.

[Italian intersocietary consensus document on aspirin therapy in primary cardiovascular prevention].

The indications for the use of aspirin in primary cardiovascular prevention continue to be a source of intense debate, with major international guidelines providing conflicting advices. This document, written by delegates of the main Italian scientific societies dealing with cardiovascular prevention and modeled on a similar document by the European Society of Cardiology Working Group on Thrombosis, reviews the evidence in favor and against the use of aspirin therapy in primary prevention based on data cumulated so far, including recent data linking aspirin with cancer protection. While awaiting the results of several ongoing studies, this document argues for a pragmatic approach to the use of low-dose aspirin in primary cardiovascular prevention, and suggests 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.

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.

Anticoagulants (heparin, low molecular weight heparin and oral anticoagulants) for intermittent claudication.

Background: Anticoagulant treatment for intermittent claudication might improve functional capacity and prevent acute cardiovascular complications caused by peripheral obstructive arterial disease. This is an update of the review first published in 2001.

Objectives: To assess the effects of anticoagulant drugs (heparin, low molecular weight heparin (LMWH) and oral anticoagulants) in patients with intermittent claudication (Fontaine stage II) in terms of improving walking capacity (pain-free walking distance or absolute walking distance), mortality, cardiovascular events, ankle/brachial pressure index, progression to surgery, amputation-free survival and side effects of these drugs.

Development and use of sulodexide in vascular diseases: implications for treatment.

Sulodexide (SDX), a sulfated polysaccharide complex extracted from porcine intestinal mucosa, is a blend of two glycosaminoglycan (GAG) entities, namely a fast-moving heparin (HP) fraction and a dermatan sulfate (DS; 20%) component. The compound is unique among HP-like substances in that it is biologically active by both the parenteral and oral routes. A main feature of the agent is to undergo extensive absorption by the vascular endothelium.

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

Three new oral anticoagulant agents were tested versus warfarin in separate, large phase III randomized clinical trials for prevention of any stroke and systemic embolism in atrial fibrillation. Dabigatran, a direct thrombin inhibitor, is at 110 mg bid non-inferior and at 150 mg bid superior to warfarin; rivaroxaban, a factor X inhibitor, is also non-inferior, and apixaban, also a factor X inhibitor, is superior to warfarin on the same efficacy end point. Statistical analysis of subgroups does not suggest, for any of the tested drugs, major differences in relation to different risk levels and history of previous stroke/TIA.

[Aspirin in primary prevention of cardiovascular diseases: how to balance risks and benefits].

While the use of aspirin in the secondary prevention of cardiovascular atherothrombotic disease is well established, many aspects of primary prevention are still unclear. Uncertainties mostly depend on a doubtful risk-benefit ratio, because of the low atherothrombotic risk of populations involved on the one hand, and the non-negligible bleeding risk of treatment on the other. Areas of specific doubt are those of diabetes and asymptomatic peripheral arterial disease, where neither single trials nor meta-analyses allow issuing high-grade specific recommendations at the moment.

Antiplatelet therapy: controversial aspects.

Although the efficacy of antiplatelet therapy is supported by numerous studies areas of uncertainty and doubt persist both in secondary and in primary prevention. In both settings it can be surmised that, with few exceptions, the relative risk reduction obtained, for instance, with aspirin, is rather uniform across the different clinical conditions and measures "efficacy" of the drug: while the absolute risk reduction varies according to the risk levels of the different conditions, and expresses the "efficiency" of the treatment. Especially in conditions at high risk as the acute coronary syndrome (ACS) the problem of "variability of response" or "resistance" to antiaggregating drugs is of remarkable importance.

Antiplatelet drugs--do we need new options? With a reappraisal of direct thromboxane inhibitors.

This review describes the current status of antiplatelet therapy in prevention of cardiovascular events of an atherothrombotic nature. The efficacy of aspirin clearly outweighs bleeding risk in secondary prevention, with the relevant exception of patients with peripheral arterial disease (PAD). In trials of primary prevention, aspirin has a limited advantage, which is challenged by the risk of major bleeding.

Approaches to prevention of cardiovascular complications and events in diabetes mellitus.

Diabetes mellitus affects about 8% of the adult population. The estimated number of patients with diabetes, presently about 170 million people, is expected to increase by 50-70% within the next 25 years. Diabetes is an important component of the complex of 'common' cardiovascular risk factors, and is responsible for acceleration and worsening of atherothrombosis.

Evaluation of thermal water in patients with functional dyspepsia and irritable bowel syndrome accompanying constipation.

Aim: To evaluate the efficacy of water supplementation treatment in patients with functional dyspepsia or irritable bowel syndrome (IBS) accompanying predominant constipation.

Methods: A total of 3872 patients with functional dyspepsia and 3609 patients with irritable bowel syndrome were enrolled in the study by 18 Italina thermal centres. Patients underwent a first cycle of thermal therapy for 21 d.

Endothelin-1 response to mental stress in early ischemic lesions of the extremities due to systemic sclerosis.

We studied circulating levels of endothelin-1, catecholamines and nitric oxide after a mental arithmetic test in 14 patients with early ischemic lesions of the extremities due to systemic sclerosis and slightly impaired peripheral vascular flow. The test induced an increase (P<0.01) in blood pressure, heart rate, endothelin-1 and catecholamine levels, whereas it did not change the low basal levels of nitric oxide.

Asymptomatic carotid stenosis: natural history and therapeutic implications.

Carotid plaques with different degrees of carotid stenosis are a common condition in the aged population (10% or more after age 75). If the definition of "symptomatic"carotid stenosis (SCS) indicates association with homolateral neurologic hemispheric lesions and/or retinal deficits even in absence of ischemic changes at CT scan, the overwhelming majority of carotid stenoses can be defined asymptomatic (ACS). Considering the low absolute risk of ipsilateral stroke,the additional risk of myocardial infarction, and the perioperative risk, surgery although beneficial in relative terms, should not be applied indiscriminately but rather in selected cases.

Picotamide, a combined inhibitor of thromboxane A2 synthase and receptor, reduces 2-year mortality in diabetics with peripheral arterial disease: the DAVID study.

Aims: Patients with diabetes are at excessive risk of mortality and cardiovascular morbidity. Previous studies suggest that aspirin may be less effective in diabetic patients. In this multi-centre, randomized, double blind trial picotamide, a dual inhibitor of thromboxane A2 synthase and receptor, was compared with aspirin for the prevention of mortality and major cardiovascular events in diabetics with peripheral arterial disease (PAD).

Opioid peptide response to spinal cord stimulation in chronic critical limb ischemia.

Twelve patients with chronic critical limb ischemia in whom a spinal cord stimulation (SCS) system had been implanted for at least one year had increased microvascular flow and achieved healing of trophic acral lesions. After switching off the system, the clinical improvement persisted for 10 days and the neurohormonal pattern showed high plasma values of beta-endorphin and Met-enkephalin, normal dynorphin B, endothelin-1 and catecholamines, and low nitric oxide. Met-enkephalin levels were further increased (P < 0.

Predictive value of D-dimer test for recurrent venous thromboembolism after anticoagulation withdrawal in subjects with a previous idiopathic event and in carriers of congenital thrombophilia.

Background: We have shown that normal D-dimer levels obtained after the discontinuation of oral anticoagulant treatment (OAT) has a high negative predictive value for recurrent venous thromboembolism (VTE). The aim of the present study was to assess the predictive value of D-dimer for recurrent VTE in subjects with a previous unprovoked event who are either carriers of inherited thrombophilia or not.

Methods And Results: We prospectively evaluated 599 patients (301 males) with a previous VTE episode.