In atherosclerosis, matrix metallopeptidases (MMPs) contribute to plaque rupture through weakening of the fibrous cap. Pleiotropic P2X purinoceptor 7 (P2X7), expressed in the carotid plaque (PL), is involved in interleukin 1 beta (IL-1β) release that may influence MMP9 generation, thus their possible modulation through acting on P2X7 was investigated. P2X7-related machinery was characterized and the effects of P2X7 antagonists (A740003, KN62) and MMPs inhibitors (Batimastat, Ro28-2653) were studied inex-vivotissue cultures of human PL’s vs. non-atherosclerotic internal mammary artery (IMA) by using molecular biology, immune-biochemical and microscopy methodologies. We highlighted atherosclerosis-related differences between PLs and IMAs molecular patterns, and their responsivity to P2X7 antagonism. High IL-1β tissue content was associated with PLs morphology and instability/vulnerability. We demonstrated that A740003, but not KN62, decreased IL-1β and MMP9 independently from NLR family pyrin domain containing 3, but in relationship with patient’s smoking status. Acting downstream P2X7 by MMPs inhibitors, diminished IL-1β mRNA without transcriptional effect at MMP9, possibly because the assumption of statin by patients. These data firstly demonstrated A740003 suitability as a specific tool to decrease inflammatory status in human vessels and might support the design of studies applying P2X7 antagonists for the local targeting and tailored therapy of atherosclerosis.

Objectives: A high rate of thrombotic events has been reported in COVID-19 population. The study aims to assess the incidence of deep vein thrombosis (DVT) in COVID-19 patients admitted to a single tertiary hospital. Methods: From April 2nd to April 18th, 2020, hospitalized patients with SARS-CoV-2 infection were screened by lower limb duplex ultrasound (DUS). Patients were on (low molecular weight heparin) LMWH prophylaxis in medical wards, and on therapeutic anticoagulation in intensive care unit (ICU). DVT risk factors, reported by the Padua prediction score and blood tests, were retrieved from institutional electronic charts. The study primary endpoint was the incidence of DVT in the in-hospital COVID-19 population and its association with clinical and laboratory risk factors. The secondary endpoint was the association of DVT with mortality. Results: Two hundred patients (median age 62 years, 72% male, 40 in ICU) received DUS screening. DVT was observed in 29 patients (14.5%), with proximal extension in 16 patients, and in association with symptoms in four patients. The DVT rate was similar in ICU (12.5%) and non-ICU patients (15%). Eighty-seven patients underwent a computed tomography angiography (CTA) that showed pulmonary embolism in 35 patients (40.2%) not associated with DVT in 25/35 cases (71.4%). DVT in the ten patients with pulmonary embolism were symptomatic in four and with a proximal localization in eight cases. A D-dimer level ≥5 mg/l at admission was predictive of DVT (OR 1.02; IC95% 1.03-1.16; p = .003). At the multivariate analysis in-hospital mortality was predicted by age (OR 1.06; 95% CI 0.02-1.15; p = .004) and by being an ICU patient (OR 1.23; 95% CI 0.30-2.25; p = .01). Conclusions: Despite LMWH prophylaxis or full anticoagulant therapy, the incidence of DVT, mainly asymptomatic, in hospitalized COVID-19 patients was 14.5%. Further research should focus on the appropriate antithrombotic therapy for COVID-19 patients.

• Heparin resistance is a phenomenon defined as the need for high-dose unfractionated heparin to achieve the target activated partial-thromboplastin time ratio. • This case aims to describe a Covid-19 patient with acute limb ischemia who developed heparin resistance. • Covid-19 infection is a systemic endothelial disease not limited to the lungs. • Anticoagulation cannot be managed as one-size-fits-all owing to the coexistence of several “sheds of thrombophilia” (i.e. HR, deficiency of antithrombin III).

Summary: The number of endovascular interventional procedures for catheter-based therapy (CBT) of acute venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), has been increasing over the past years. The development of more efficient thrombectomy systems for CBT of VTE has potentially enhanced the efficacy of interventional treatment of VTE. Nevertheless, indications for CBT of VTE, i.e. catheter-directed thrombolysis (CDT) or catheter-based mechanical thrombus removal, need to be established based on existing data and expert consensus. Vascular experts should be involved in the decision-making process on CBTs in patients with acute VTE, and thrombus removal procedures should be performed in centers with experience in interventional treatment of VTE. This guideline document of the European Society of Vascular Medicine (ESVM) provides recommendations on indications and management of CBT in acute VTE and is endorsed by the European national societies of Vascular Medicine.

Recanalization of the saphenous vein trunk after endovenous radiofrequency ablation (RFA) is often associated with recurrent varicose veins (RVVs) or recanalization. This study aimed to assess the long-term results of RFA of the great saphenous vein (GSV) and identify the risk factors for GSV recanalization and RVVs during follow-up for patients presenting to dedicated outpatient vein centers. All consecutive patients with incompetent GSVs who underwent RFA between 2009 and 2019 were retrospectively analyzed. The primary study end points were freedom from GSV recanalization and the RVV rate during follow-up. The secondary study end points were the postoperative complication rate and the risk factors for GSV recanalization and RVVs. Univariate and multivariate analyses were performed to identify the potential risk factors for GSV recanalization and RVVs. During the study period, 1568 limbs were treated in 1300 consecutive patients (mean age, 53.5 ± 12.9 years; 71.9% women; CEAP [clinical, etiology, anatomy, pathophysiology] C2-C6; venous clinical severity score >5). Technical success was achieved in 99.7% of cases. At a mean follow-up of 57.2 ± 25.4 months, the GSV occlusion and freedom from reintervention rates were 100% and 100% within 1 week, 97% and 95.7% at 1 year, 95.2% and 93.1% at 3 years, and 92.4% and 92.8% at 5 years, respectively. The recurrence rate was 10% (n = 158) during the follow-up period. On multivariate analysis, a direct confluence of the accessory saphenous vein into the saphenofemoral junction (odds ratio [OR], 1.561; 95% confidence interval [CI], 1.0-7.04; P = .032), a history of pregnancy >2 (OR, 3.68; 95% CI, 1.19-11.36; P = .023), C4 (OR, 6.41; 95% CI, 1.36-30.28; P = .019), and preoperative GSV diameter >10 mm (OR, 1.82; 95% CI, 1.65-4.03; P = .043) were risk factors for GSV recanalization. Moreover, age >70 years (OR, 1.04; 95% CI, 1.01-1.06; P = .014) and incompetent perforator veins (OR, 1.17; 95% CI, 0.65-2.03; P = .018) were also risk factors for RVVs. RFA is a safe technique to ablate the GSV with a low complication rate and durability during 5 years of follow-up. However, patients with a high clinical score and those with direct confluence of the accessory saphenous vein into the saphenofemoral junction experienced higher long-term GSV recanalization and RVV rates.