Prevalence and determinants of serum antibodies to SARS-CoV-2 in the general population of the Gardena valley.

Estimating the spread of SARS-CoV-2 infection in communities is critical. We surveyed 2244 stratified random sample community members of the Gardena valley, a winter touristic area, amidst the first expansion phase of the COVID-19 pandemic in Europe. We measured agreement between Diasorin and Abbott serum bioassay outputs and the Abbott optimal discriminant threshold of serum neutralisation titres with recursive receiver operating characteristic curve. We analytically adjusted serum antibody tests for unbiased seroprevalence estimate and analysed the determinants of infection with non-response weighted multiple logistic regression. SARS-CoV-2 seroprevalence was 26.9% (95% CI 25.2-28.6) by June 2020. The bioassays had a modest agreement with each other. At a lower threshold than the manufacturer's recommended level, the Abbott assay reflected greater discrimination of serum neutralisation capacity. Seropositivity was associated with place and economic activity, not with sex or age. Symptoms like fever and weakness were age-dependent. SARS-CoV-2 mitigation strategies should account for context in high prevalence areas.

Comparison of Once-Daily Bemiparin with Twice-Daily Enoxaparin for Acute Deep Vein Thrombosis: A Multicenter, Open-Label, Randomized Controlled Trial.

BACKGROUND: Individuals with deep vein thrombosis (DVT) have an increased risk of pulmonary embolism (PE), death, and long-term thrombotic complications. OBJECTIVES: To evaluate the efficacy and safety of bemiparin once daily versus enoxaparin twice daily in the treatment of acute DVT, and to establish therapeutic non-inferiority of bemiparin. PATIENTS AND METHODS: This multicenter, randomized, open-label, active-controlled phase III clinical trial enrolled patients with acute proximal DVT confirmed by complete compression ultrasound (CCUS). Patients received bemiparin once daily or enoxaparin twice daily subcutaneously for 7 days, in combination with warfarin 5 mg/day. Assessment of thrombotic burden was blinded and used CCUS recordings. The primary efficacy endpoint was the percentage of patients with an improvement in thrombotic burden at day 83 (end of follow-up); the secondary efficacy endpoint was the incidence of symptomatic recurrent DVT and PE. Safety endpoints included treatment-emergent adverse events. RESULTS: Three-hundred and twelve patients were enrolled (~ 62% male; mean age 55.2 years). At least one DVT risk factor was present in 26.1% and 28.7% of the bemiparin and enoxaparin groups, respectively. The proportion of patients who had an improvement in thrombotic burden was similar for bemiparin (78.2%) and enoxaparin [80.8%; difference - 2.66 (97.5% CI - 12.39; ∞)], as was mean change in thrombus score (- 8.8 and - 8.6, respectively). There were no cases of recurrent DVT, and one case of non-fatal symptomatic PE in each treatment group. No major bleeding was reported, and there was no difference in the incidence of non-major bleeding. CONCLUSIONS: The efficacy of bemiparin administered once daily is non-inferior to that of enoxaparin administered twice daily with a similar safety profile. CLINICALTRIALS. GOV IDENTIFIER: NCT01880216.

The quality of anticoagulation on functional outcome and mortality for TIA/stroke in atrial fibrillation patients.

BACKGROUND: In atrial fibrillation (AF) patients stroke is nearly twice as likely to be fatal as non-AF patients and functional deficits are more likely to be severe among survivors. The incidence of stroke among AF patients is greatly reduced by oral anticoagulant treatment (OAT). However, fluctuation of anticoagulation levels is intrinsically related to OAT and often international normalized ratio (INR) is out of the therapeutic range. METHODS: Since the "anticoagulation history" is an ongoing process, we performed this prospective study in 578 AF patients to investigate the role of the whole quality of OAT and of INR levels at the occurrence of transient ischemic attack (TIA) or stroke on the severity of cerebral ischemia. RESULTS: During follow-up 13 patients had TIA and 18 had stroke (rate 1.67 x 100 pt/years). In relation to the quality of anticoagulant treatment, no significant differences were found in the time spent below and within the intended therapeutic range, between patients with and without TIA/stroke. Patients with TIA/stroke spent a longer time above the intended therapeutic range with respect to other patients, even if this difference was not confirmed at multivariate analysis. Forty-six percent of patients with TIA and 66% of patients with stroke had INR>or=2 at the occurrence of ischemic event. CONCLUSION: The severity of stroke was not related to the whole quality of anticoagulation or to INR at the event.

Venous thromboembolism prevention in patients with heart failure: an often neglected issue.

Several epidemiological studies have shown a high prevalence of venous thromboembolism (VTE) complications in patients with acute heart failure; in addition, the level of risk associated with this disease is notable, ranging from 15 to 30%. Three large clinical trials have clearly demonstrated the efficacy and safety of pharmacological prophylaxis in internal medicine patients hospitalized for an acute medical disease; on the contrary, until now there are no studies which have evaluated antithrombotic prophylaxis in a selected population of patients with heart failure only. Moreover, discrepancies existing among recommendations reported in different guidelines may produce uncertainties in the management of VTE prevention in patients with heart failure and may contribute to an underuse of thromboprophylaxis in the daily clinical practice. The aim of this review is to analyze the existing evidence about VTE risk in patients with heart failure as well as the efficacy and safety of antithrombotic prevention, and to underline which are the most important unmet clinical issues for the optimal management of thromboprophylaxis in this particular clinical setting.

Risk of bleeding in very old atrial fibrillation patients on warfarin: relationship with ageing and CHADS2 score.

AIMS: In atrial fibrillation (AF) patients, age >or=75 years is one of the major risk factors for stroke. However, it is not clear if an upper limit for the indication to OAT exists. METHODS AND RESULTS: For this reason, we performed a prospective study on 290 AF patients on OAT aged >or=75 years (median age 82 years, total follow-up period 814 pt/years) followed by our Anticoagulation Clinic. Seventeen major bleeding events were recorded (rate 2.1 x 100 pt/years), 11 of which cerebral (1.35 x 100 pt/years). The occurrence of major bleedings was associated with history of previous TIA or stroke [OR 3.4 (1.1-12.5), p=0.01] and with diabetes [OR 4.4 (1.3-14.7) p=0.01]. We found a trend to a progressive increase in the rate of bleeding risk with the increase of the CHADS2 score: patients with score 4-6 showed a rate of 3.4 x 100 pt/years with respect to 1.5 x 100 pt/years of patients with lower score. Number Needed to Harm (NNH) was calculated in relation to different classes of age (75-89, 80-84, >or=85 years) and to CHADS2 score. For patients in CHADS2 score 1-3 NNH remained stable across the different age classes. Instead for patients in CHADS2 score 4-6, NNH varied among the 3 groups of ages, reaching a value of 10 in patients >or=85 years. CONCLUSION: Our data suggest that: 1) in AF patients older than 75 years with CHADS2 score 1-3 the risk of bleeding is low, 2) in AF patients >85 years with CHADS2 4-6 the risk of bleeding is high so that the use of OAT should be highly individualised.

Cardiovascular and thrombophilic risk factors in patients with retinal artery occlusion.

This article evaluates the prevalence of cardiovascular and thrombophilic risk factors in patients with retinal artery occlusion. Forty-one patients with a first episode of a retinal artery occlusion underwent complete ophthalmic examination, routine blood testing and specific laboratory tests for thrombophilia, such as fasting and postmethionine homocysteine, lipoprotein(a), plasminogen activator inhibitor-1, factor VIII, factor V Leiden, factor II G20210A polymorphism, lupus anticoagulant and anticardiolipin antibodies. The control population consisted of 100 healthy individuals comparable as regards age and sex. At univariate analysis, hypertension, smoking, dyslipidaemia (both high cholesterol and triglyceride levels), antiphospholipid antibodies, hyperhomocysteinaemia, elevated factor VIII and lipoprotein(a) levels were significantly associated with retinal artery occlusion; at multivariate analysis, adjusted for age, sex, traditional and thrombophilic risk factors, smoking, hypercholesterolaemia, elevated homocysteine and lipoprotein(a) levels confirmed their independent role as risk factors for retinal artery occlusion. In conclusion, the results of the present pilot study demonstrate that the prevalence of hypercholesterolaemia and smoking and the 'thrombophilic burden' are increased in patients with retinal artery occlusion. Our findings may have implications for the management of these patients, suggesting the need for an intensive and tailored secondary prevention and new therapeutic approaches.

Frequency and localization of mutations in the 106 exons of the RYR1 gene in 50 individuals with malignant hyperthermia.

Malignant hyperthermia (MH) is a dominantly inherited pharmacogenetic condition that manifests as a life-threatening hypermetabolic reaction when a susceptible individual is exposed to common volatile anesthetics and depolarizing muscle relaxants. Although MH appears to be genetically heterogeneous, RYR1 is the main candidate for MH susceptibility. However, since molecular analysis is generally limited to exons where mutations are more frequently detected, these are routinely found only in 30-50% of susceptible subjects. In this study the entire RYR1 coding region was analyzed in a cohort of 50 Italian MH susceptible (MHS) subjects. Thirty-one mutations, 16 of which were novel, were found in 43 individuals with a mutation detection rate of 86%, the highest reported for RYR1 in MH so far. These data provide clear evidence that mutations in the RYR1 gene are the predominant cause of MH.

TAFI activity and antigen plasma levels are not increased in acute coronary artery disease patients admitted to a coronary care unit.

INTRODUCTION: Hypofibrinolysis, at least in part due to high levels of plasminogen activator inhibitor-1 (PAI-1), has been reported to occur frequently in patients with coronary artery disease (CAD). A recently described carboxypeptidase, thrombin-activatable fibrinolysis inhibitor (TAFI), is involved in the regulation of the balance between coagulation and fibrinolysis. High TAFI plasma levels may therefore contribute to a hypofibrinolytic state and to an increased risk for thrombotic disorders. There are contradictory results regarding TAFI levels in CAD patients, possibly because the characteristics of patients investigated and the time of blood sampling were different among different studies. MATERIALS AND METHODS: Fibrinolytic inhibitors (TAFI activity, TAFI antigen and PAI-1 activity plasma levels) were measured in 44 consecutive patients admitted to the Coronary Care Unit of the University of Florence and in a group of 44 healthy controls, matched for age and sex, to detect a possible association of their levels with acute CAD. RESULTS: No differences were found in TAFI levels, either activity or antigen, between patients and controls. PAI-1 activity was significant different between patients and controls (p=0.0001). The frequencies of TAFI activity and antigen over cut-off levels were similar in patients and controls. Instead, higher PAI-1 levels were more frequent (p=0.04) in patients respect to controls. The univariate analysis confirmed the association of increased PAI-1 levels with acute CAD [OR=3.3; p=0.04]. Among the patients, TAFI and PAI-1 levels were not different according to clinical presentation of symptoms or indication to immediate percutaneous revascularization. CONCLUSION: Our study suggests that in acute phase of CAD no increased levels of TAFI are detectable in plasma.

Prophylaxis and treatment of venous thromboembolism in patients with cancer: an update.

The close correlation between venous thromboembolism (VTE) and cancer has been known for some time, and numerous reports in the literature have highlighted the epidemiological significance. Moreover, VTE has a substantial impact on morbidity and mortality in oncological patients. The prevention and treatment of VTE are important aspects of the clinical management of patients with cancer. The presence of a tumour is often associated with thrombotic complications that are more difficult to diagnose, and sometimes make the treatment of VTE less effective and more likely to cause haemorrhages.

eNOS G894T polymorphism as a mild predisposing factor for abdominal aortic aneurysm.

OBJECTIVE: Abdominal aortic aneurysm (AAA) represents a chronic degenerative condition associated with atherosclerosis. Actually, data from experimental and clinical studies suggest that nitric oxide (NO) is a modulator in maintaining endothelial function and antithrombotic intravascular environment. Reduced vascular NO generation in subjects carrying the rare variants of the eNOS gene might predispose to AAA. No information is available about the influence of the eNOS gene T-786C, G894T, and 4a/4b polymorphisms in the susceptibility to the disease. METHODS: In this study, we evaluated the role of these polymorphisms in the predisposition to AAA and their influence in hypertensive and normotensive patients. We studied 250 consecutive patients with AAA referred to the Unit of Vascular Surgery of the University of Florence compared with 250 truly healthy subjects with a negative history of vascular diseases. All subjects, patients, and controls, underwent duplex scanning examination, and to assess the presence of other atherosclerotic localizations, all patients underwent clinical and instrumental examinations. RESULTS: A significant difference in genotype distribution and allele frequency was observed for eNOS G894T but not for T-786C and 4a/4b polymorphisms. At the multivariate analysis after adjustment for traditional vascular risk factors and other atherosclerotic localizations, the eNOS 894T variant was significantly associated with AAA, according to dominant and recessive models (dominant model odds ratio [OR]: 2.2, 95% confidence interval [CI]: 1.21-3.93, P = .007; recessive model OR: 2.7, 95% CI: 1.42-5.20, P = .002). When patients with other atherosclerotic localizations were excluded from the analysis, the 894T variant still remained associated with the predisposition to AAA, according to the models considered (dominant model OR: 2.1, 95%CI: 1.23-3.92, P = .007; recessive model OR: 2.8, 95%CI: 1.45-5.24, P = .002). CONCLUSIONS: The present study showed that the eNOS G894T polymorphism is a mild modulator of the predisposition to AAA apart from traditional risk factors, suggesting a genetic influence on the molecular mechanisms responsible for this complex disease.

[Prophylaxis and treatment of venous thromboembolism: the role of new antithrombotic drugs]. / Nuovi farmaci antitrombotici per la profilassi e la terapia del tromboembolismo venoso.

Venous thromboembolic disease (VTE) is a major cause of morbidity and mortality. Unfractioned heparin, low-molecular weight heparins and vitamin K antagonists, currently used in the prophylaxis and treatment of VTE, are effective and relatively safe. Otherwise, they have some important limitations (narrow therapeutic window, highly variable dose-response relationship; limitation by the need of parenteral administration for heparins and the risk of heparin-induced thrombocytopenia) which provide opportunities for new antithrombotic drugs. These drugs include: inhibitors of factors IXa and factor VIIa/tissue factor complex, agents that enhance the protein C anticoagulant pathway, direct and antithrombin-dependent Xa inhibitors, direct and indirect thrombin inhibitors. Fondaparinux and idraparinux, two new indirect parenteral factor Xa inhibitors, have been studied in well conducted trials, showing interesting results both in the prevention and in the treatment of VTE. Ximelagatran, the first orally available thrombin inhibitor, represents a promising new anticoagulant drug for the prophylaxis of VTE after major orthopedic surgery and for the treatment of deep vein thrombosis.