Venous thromboembolism (VTE) is the third most common cause of death worldwide. The incidence of VTE varies according to different countries, ranging from 1–2 per 1000 person-years in Western Countries, while it is lower in Eastern Countries (70 per 1000 person-years) and lowest in breast, melanoma and prostate cancer (<20 per 1000 person-years). In this comprehensive review, we summarized the prevalence of different risk factors for VTE and the potential molecular mechanisms/pathogenetic mediators leading to VTE.

The role of oxidative stress in the onset and progression of atherosclerosis and its impact on the development of cardiovascular events has been widely described. Thus, increased oxidative stress has been described in several atherosclerotic risk factors, such as hypertension, dyslipidaemia, peripheral artery disease, metabolic syndrome, diabetes, and obesity. Among others, specific oxidative pathways involving both pro-oxidant and antioxidant enzymes seem to play a major role in the production of reactive oxidant species (ROS), such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, myeloperoxidase, superoxide dismutase, and glutathione peroxidase. In this review, we will discuss: 1) the most relevant enzyme systems involved in the formation and detoxification of ROS, 2) the relationship between oxidative stress and cardiovascular risk, and 3) therapeutic implications to modulate oxidative stress. The role of oxidative stress in the onset and progression of atherosclerosis and its impact on the development of cardiovascular events has been widely described. Thus, increased oxidative stress has been described in several atherosclerotic risk factors, such as hypertension, dyslipidaemia, peripheral artery disease, metabolic syndrome, diabetes, and obesity. Among others, specific oxidative pathways involving both pro-oxidant and antioxidant enzymes seem to play a major role in the production of reactive oxidant species (ROS), such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, myeloperoxidase, superoxide dismutase, and glutathione peroxidase. In this review, we will discuss: 1) the most relevant enzyme systems involved in the formation and detoxification of ROS, 2) the relationship between oxidative stress and cardiovascular risk, and 3) therapeutic implications to modulate oxidative stress.

Background: Gut microbiota is emerging as a novel risk factor for atherothrombosis, but the predictive role of gut‐derived lipopolysaccharide ( LPS ) is unknown. We analyzed (1) the association between LPS and major adverse cardiovascular events ( MACE ) in atrial fibrillation ( AF ) and (2) its relationship with adherence to a Mediterranean diet (Med‐diet). Methods and Results: This was a prospective single‐center study including 912 AF patients treated with vitamin K antagonists (3716 patient‐years). The primary end point was a composite of MACE . Baseline serum LPS , adherence to Med‐diet (n=704), and urinary excretion of 11‐dehydro‐thromboxane B ₂ (TxB ₂ , n=852) were investigated. Mean age was 73.5 years; 42.9% were women. A total of 187 MACE (5.0% per year) occurred: 54, 59, and 74 in the first, second, and third tertile of LPS , respectively (log‐rank test P =0.004). Log‐ LPS (hazard ratio 1.194, P =0.009), age (hazard ratio 1.083, P <0.001), and previous cerebrovascular (hazard ratio 1.634, P =0.004) and cardiac events (hazard ratio 1.822, P <0.001) were predictors of MACE . In the whole cohort, AF (versus sinus rhythm) (β 0.087, P =0.014) and low‐density lipoprotein cholesterol (β 0.069, P =0.049) were associated with circulating LPS . Furthermore, Med‐diet score (β −0.137, P <0.001) was predictive of log‐ LPS , with fruits (β −0.083, P =0.030) and legumes (β −0.120, P =0.002) negatively associated with log‐ LPS levels. Log‐ LPS and log‐TxB ₂ were highly correlated (r=0.598, P <0.001). Log‐ LPS (β 0.574, P <0.001) and Med‐diet score (β −0.218, P <0.001) were significantly associated with baseline urinary excretion of TxB ₂ . Conclusions: In this cohort of AF patients, LPS levels were predictive of MACE and negatively affected by high adherence to Med‐diet. LPS may contribute to MACE incidence in AF by increasing platelet activation.

Background: To systematically review clinical and biochemical characteristics associated with the severity of the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐related disease (COVID‐19).Materials and methods: Systematic review of observational studies from PubMed, ISI Web of Science, SCOPUS and Cochrane databases including people affected by COVID‐19 and reporting data according to the severity of the disease. Data were combined with odds ratio (OR) and metanalysed. Severe COVID‐19 was defined by acute respiratory distress syndrome, intensive care unit admission and death.Results: We included 12 studies with 2794 patients, of whom 596 (21.33%) had severe disease. A slightly higher age was found in severe vs non‐severe disease. We found that prevalent cerebrovascular disease (odds ratio [OR] 3.66, 95% confidence interval [CI] 1.73‐7.72), chronic obstructive pulmonary disease (OR: 2.39, 95% CI 1.10‐5.19), prevalent cardiovascular disease (OR: 2.84, 95% CI 1.59‐5.10), diabetes (OR: 2.78, 95% CI 2.09‐3.72), hypertension (OR: 2.24, 95% CI 1.63‐3.08), smoking (OR: 1.54, 95% CI 1.07‐2.22) and male sex (OR: 1.22, 95% CI 1.01‐1.49) were associated with severe disease. Furthermore, increased procalcitonin (OR: 8.21, 95% CI 4.48‐15.07), increased D‐Dimer (OR: 5.67, 95% CI 1.45‐22.16) and thrombocytopenia (OR: 3.61, 95% CI 2.62‐4.97) predicted severe infection.Conclusion: Characteristics associated with the severity of SARS‐CoV‐2 infection may allow an early identification and management of patients with poor outcomes.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombotic manifestations and/or pregnancy-related complications in patients with persistently high antiphospholipid antibodies (aPL), the most common being represented by anticardiolipin antibodies (aCL), anti-beta 2 glycoprotein-I (aβ2GPI) and lupus anticoagulant (LAC). A growing number of studies showed that in some cases patients may present with clinical features of APS but with temporary positive or persistently negative titers of aPL. For these patients, the definition of seronegative APS (SN-APS) has been proposed. Nevertheless, the negativity to classic criteria aPL, does not imply that other antibodies may be present and involved in the onset of thrombosis. The diagnosis of SN-APS is usually made by exclusion, but its recognition is important to adopt the most appropriate anti-thrombotic strategy to reduce the rate of recurrences. This research is in continuous development as the clinical relevance of these antibodies is far from being completely clarified. The most studied antibodies are those against phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, vimentin/cardiolipin complex, and annexin A5. Moreover, the assays to measure the levels of these antibodies are not yet standardized. In this review, we will summarize the evidence on the most studied non-criteria aPL, their potential clinical relevance and the antithrombotic therapeutic strategies available in the setting of APS and SN-APS.