Prognostic role of neutrophils to lymphocytes ratio in patients with acute pulmonary embolism: a systematic review and meta-analysis of the literature

The prognostic assessment of patients with acute pulmonary embolism (PE) is essential to drive its management. The search for new prognostic factors is a central issue for a more accurate estimate of short-term adverse events. Circulating neutrophils/lymphocytes ratio (NLR) has been suggested as prognostic biomarker for different cardiovascular diseases. Given the central role of inflammation, and in particular of neutrophils in the pathogenesis of VTE and its clinical history, NLR might represent a prognostic tool also in this setting. We performed a systematic review and meta-analysis of the literature to assess the prognostic role of NLR in patients with acute PE. MEDLINE and EMBASE were searched up to 2017, week 21. A bivariate random-effects regression approach was used to obtain summary estimate of accuracy of the high NLR adjusting for inter-study variability. Six studies for a total of 1424 patient are included. High NLR has a weighted mean sensitivity of 77% (95% CI 68-83) and a weighted mean specificity of 74% (95% CI 68-79). High NLR positive and negative predictive values are 24.4% (95% CI 20.4-28.3) and 96.7% (95% CI 95.6-97.8), respectively. The relevant impact of NLR on short-term mortality after an acute PE makes it a promising biomarker to better stratify patient prognosis

Follow-up management of patients receiving direct oral anticoagulants

Over the last years, direct oral anticoagulants (DOACs) have radically changed and simplified the therapeutic approach and management of patients on anticoagulant therapy. For these patients, international guidelines recommend to set up a regular follow-up (every 1-6 months) to re-enforce education, to ensure adequate adherence and persistence to treatment. In real-life setting, the application of the suggested follow-up regimens and incidence rates of thrombotic and bleeding complications related to the intensity of follow-up strategies has not been described. We conducted a multicentre, retrospective study at 4 Italian Thrombosis Centres to describe follow-up strategies of patients on DOACs treatment and to assess the incidence of bleeding and thrombotic complications. We enrolled 534 patients, with median follow-up 24 months: 52.1% had\u2009<\u20093 visits/year (group 1), while 47.9% required\u2009 65\u20093 visits/year (group 2). Mean age and gender were similar between the 2 groups, while severe anaemia (4.4% and 1.2%, p 0.03) and creatinine clearance\u2009<\u200950 mL/min were more common in group 2 (26.8% and 17.8%, p 0.02). The incidence of thromboembolic events was 3.9% in group 2 and 1.1% in group 1 (p 0.03). Major bleeding rates were non-significantly higher in group 2, whereas non-major bleeding rates occurred significantly more frequently in group 2 (26.6% and 18.7%, respectively, p 0.03). A tailored follow-up program is of critical importance to correctly manage patients on DOACs. A less intense follow-up management is feasible and safe for a substantial proportion of patients, provided they are carefully identified at specialized centres

Prevalence of Abdominal Aortic Aneurysms in the General Population and in Subgroups at High Cardiovascular Risk in Italy. Results of the RoCAV Population Based Study

Objectives: Prevalence data on abdominal aortic aneurysm (AAA) in women, subjects younger than 65 years and in subgroups carrying specific risk factors are scarce. AAA prevalence was evaluated in an Italian population including women and younger subjects, stratifying for the presence of cardiovascular disease (CVD) risk factors and CVD risk score. Materials and methods: A population based cross-sectional study was conducted between 2013 and 2016. Men aged 50-75 and women aged 60-75 years, resident in the city of Varese (northern Italy), were randomly selected from the civil registry. A vascular surgeon performed an abdominal aortic ultrasound scan at four sites using the leading edge to leading edge method. CVD risk score was computed using the ESC-SCORE algorithm. The age and gender specific prevalence was estimated, stratifying by the presence of CVD and cardiovascular risk factors. Results: Among the 3755 subjects with a valid ultrasound measurement, 63 subjects with an AAA were identified (5 referred for surgical intervention), among whom 34 were not previously known (30 men 1.3%, 95% CI 0.9-1.8; 4 women 0.3%, 95% CI 0.1-0.8). Considering age classes in men only, the highest prevalence of screen detected AAA was found in subjects aged 65-70 (1.2%; 95% CI 0.4-2.5) and 70-75 (2.5%; 95% CI 1.4-4.0) years. Among 65-75 year old men, the highest AAA prevalence was found in subjects with a previous myocardial infarction (MI 4.9%, 95% CI 2.0-9.9) and in ever-smokers reporting more than 15 pack years of smoking (4.1%, 95% CI 2.5-6.3). Among the younger subjects, those having an ESC-SCORE higher than 5% or a previous CVD (MI or stroke) showed a prevalence of 1.4% (95% CI 0.3-4.2; prevalence including subaneurysms 6.7%, 95% CI 3.7-11.0%). Conclusions: In the study population, both a general screening program in 65-75 year old men and an approach targeted to subgroups at higher risk merit evaluation in a cost-effectiveness study. In 50-64 year old men, strategies for population selection should consider CVD risk stratification tools

Very elderly patients with venous thromboembolism on oral anticoagulation with VKAs or DOACs: Results from the prospective multicenter START2-Register Study

Few data are available on the safety of anticoagulation in very elderly patients treated with Vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) for venous thromboembolism (VTE).Introduction: Few data are available on the safety of anticoagulation in very elderly patients treated with Vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) for venous thromboembolism (VTE). Methods: We carried out a prospective cohort study on VTE patients aged 6585 years enrolled in the Survey on anticoagulaTed pAtients RegisTer (START2-Register) on treatment with VKAs or DOACs, with the aim to evaluate mortality, bleeding and thrombotic rates (venous and arterial). Results: We enrolled 272 patients, 58.7% on VKA and 41.3% on DOACs. Baseline characteristics were similar between treatment groups, with a higher prevalence of renal failure in VKAs patients and of a history of bleeding and previous stroke/TIA in DOACs patients. During follow-up of 429 patient-years, 15 major and non-major clinically relevant bleedings were recorded (rate 3.5 7 100 pt-yrs), 5 were major bleeds (rate 1.2 7 100 pt-yrs), 1 in a patient on aspirin (rate 4.3 7 100 pt-yrs). Bleeding rate was higher in patients on DOACs (crude HR 4.7; 95%CI 1.5\u201315.01). Eight thrombotic events were recorded (rate 1.9 7 100 pt-yrs), 3 recurrent VTE and 5 stroke/TIA. Overall, the incidence of thrombotic events was higher in DOACs patients (crude HR 4.5; 95% CI 1.5; 13.3). The rate of recurrent VTE was similar in the two group. Mortality rate was significantly lower in DOACs patients (crude HR 0.30; 95% CI 0.1;0.9). Conclusion: A higher bleeding risk was found in very elderly VTE patients on DOACs despite the wide use of low-dosages. Similarly a higher thrombotic risk was found while the incidence of recurrent VTE was low and similar between the groups. Mortality rate were significantly lower in DOACs patients

Design and rationale of a randomized, placebo-controlled trial on the efficacy and safety of sulodexide for extended treatment in elderly patients after a first venous thromboembolism

How to prevent recurrences after a first venous thromboembolic (VTE) event in elderly patients is still an open issue, especially because of the high bleeding risk of anticoagulation in these patients. The placebo-controlled "Jason" study aims at assessing the efficacy and safety for secondary VTE prevention in elderly patients of oral Sulodexide (Vessel\uae) administration, a mixture of glycosaminoglycans (Alfasigma, Bologna, Italy) which proved effective against recurrences in a general population (SURVET study) without major bleeding (MB) complications. 1450 patients, aged\u2009 65\u200975 years, after at least 3 months of anticoagulation treatment for a first VTE episode, are double-blind randomized to receive for 12 months either sulodexide 500 lipasemic units (LSUs) twice daily, or sulodexide 250 LSU twice daily\u2009+\u2009indistinguishable placebo, or indistinguishable placebo. Primary outcomes for efficacy are the composite of death for VTE and recurrent VTE, and occurrence of MB for safety. Secondary outcomes include stroke, cardiovascular death and other thromboembolic events, and MB\u2009+\u2009clinically relevant non-MB. The first patient is scheduled to be randomized in May 2020. The study protocol has been approved by AIFA (Agenzia Italiana del Farmaco) and the Ethics Committee of the coordinating center. Written informed consent will be obtained from all patients prior to study participation. Jason study is an investigator-initiated trial, promoted by "Arianna Anticoagulazione" Foundation, Bologna, Italy, and supported by Alfasigma, Bologna, Italy. Study findings will be disseminated to participant centers, at research conferences and in peer-reviewed journals. Trial registration numbers NCT04257487; EudraCT (2019-000570-33)

Direct-acting antivirals in relapsed or refractory hepatitis C virus-associated diffuse large B-cell lymphoma

Recent studies have demonstrated feasibility and substantial benefit of direct-acting antivirals (DAAs) administration during or after first-line immune-chemotherapy (I-CT) in patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphomas (DLBCL). However, data on DAAs used during or after salvage treatments are still lacking. In this study we assessed clinical and virological outcome in 11 patients with relapsed (n = 7) or refractory (n = 4) HCV-positive DLBCL. DAAs were given either concurrently (n = 3) or subsequent (n = 8) to salvage I-CT. Most patients (10 of 11) received sofosbuvir-based regimens. All patients completed their planned courses of DAAs and achieved sustained virological response. DAAs were well tolerated, with no grade >= 2 adverse events. At a median follow-up of 3.6 years four patients died (4-year OS: 76%). In conclusion, we provide evidence that DAAs in HCV-positive relapsed/refractory DLBCL are extremely safe and effective, suggesting that they should be used if HCV eradication was not instituted before

Impact of bone marrow fibrosis grade in post-polycythemia vera and post-essential thrombocythemia myelofibrosis: A study of the MYSEC group

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