Public's perspective on COVID-19 adenovirus vector vaccines after thrombosis with thrombocytopenia syndrome (TTS) reports and associated regulatory actions: A cross-sectional study in six EU member states

Objective: In 2021, thrombosis with thrombocytopenia syndrome (TTS) was confirmed by the European Medicines Agency (EMA) as a rare side effect of the COVID-19 adenovirus vector vaccines Vaxzevria® and Jcovden®. This study aimed to describe the public's knowledge of TTS and how it affected the willingness to be vaccinated with COVID-19 vaccines and other vaccines in six European countries. Methods: From June to October of 2022, a multi-country cross-sectional online survey was conducted in Denmark, Greece, Latvia, Netherlands, Portugal, and Slovenia. The minimum target of participants to be recruited was based on the size of the country's population. The results were analysed descriptively. Results: In total, 3794 respondents were included in the analysis; across the six countries, 33.3 %–68.3 % reported being familiar with signs and symptoms of TTS, although 3.1–61.4 % of those were able to identify the symptoms correctly. The reported changes in willingness to be vaccinated against COVID-19 and with other vaccines varied per country. The largest reported change in the willingness to be vaccinated with Vaxzevria® and Jcovden® was observed in Denmark (61.2 %), while the willingness to be vaccinated with other COVID-19 vaccines changed most in Slovenia (30.4 %). The smallest decrease in willingness towards future vaccination against COVID-19 was reported in the Netherlands (20.9 %) contrasting with the largest decrease observed in Latvia (69.1 %). Conclusion: Knowledge about TTS seemed to have influenced the public's opinion in Europe resulting in less willingness to be vaccinated with Vaxzevria® and Jcovden®. Willingness for vaccination against COVID-19 with other vaccines and widespread use of vaccines to prevent other diseases also differed and seemed to be determined by the approaches taken by national health authorities when reacting to and communicating about COVID-19 vaccination risks. Further investigation of optimal risk communication strategies is warranted

Antithrombotic Treatment in Diabetes Mellitus: A Review of the Literature about Antiplatelet and Anticoagulation Strategies Used for Diabetic Patients in Primary and Secondary Prevention

Background: Diabetes mellitus (DM) is on the rise globally. Its prevalence has nearly doubled during the last two decades and it is estimated to affect 8.8% of the global population. Cardiovascular disease (CVD) is the leading cause of death in the diabetic population and despite modem anti-inflammatory and cardiopmtective therapeutic strategies, diabetic patients have at least a twice fold risk of cardiovascular events. The prothrombotic state in DM is associated with multiple determinants such as platelet alterations, oxidative stress, endothelial changes, circulating mediators. Thus, proper antithrombotic strategies to reduce the risk of CVD in this population are critical. Methods: This article reviews the current antiplatelet and anticoagulant agents in the aspect of primary and secondary prevention of CVD in the diabetic population. Results: The use of aspirin may be considered only at high-risk patients in the absence of contraindications. Cangrelor was not inferior to clopidogrel in preventing the composite outcome of CV death, myocardial infarction and revascularization without increasing major bleeding. Triple therapy in the subpopulation with DM significantly reduced the composite primary outcome of CV death, myocardial infarction or repeat target lesion revascularization. That was not the case for stent thrombosis, which was similar in both groups. importantly, triple therapy did not result in increased bleeding complications, which were similar in both groups. However, cilostazol is linked to various adverse effects (e.g., headache, palpitations, and gastrointestinal disturbances) that drive many patients to withdrawal. Conclusion: In conclusion, DM is a rapidly growing disease that increases the risk of CVD, AF, and CV mortality. Proper antithrombotic strategies to reduce CVD risk in DM are a necessity. Moreover, new antithrombotic treatments and combination therapies may play a critical role to overcome antiplatelet resistance in DM patients and reduce morbidity and mortality attributed to CVD

The association of diabetes mellitus with carotid atherosclerosis and arterial stiffness in the Corinthia study

Background and aims: Evaluation of arterial stiffness and carotid atherosclerotic burden can provide important prognostic information regarding the risk of future cardiovascular events. The aim of this study was to assess these vascular properties in patients with diabetes mellitus (DM). Methods and results: In the context of the observational “Corinthia” study, we analyzed 1757 participants with determined DM status. Carotid ultrasonography was performed to evaluate intima-media thickness (cIMT) and carotid plaque burden. Arterial stiffness was estimated via assessment of carotid-to-femoral pulse wave velocity (cfPWV). Individuals with DM had increased mean cIMT, maximum cIMT, carotid plaque burden, and cfPWV compared to those without DM. After multivariable regression analysis, the presence of DM was still associated with significantly increased mean cIMT (by 0.074 mm, p = .004), maximum cIMT (by 0.134 mm, p = .007), cfPWV (by 0.929 m/s, p < .001), and a higher prevalence of carotid plaques (odds ratio 1.52, 95% confidence intervals 1.11, 2.10, p = .01). In a propensity score-matched cohort, mean cIMT, maximum cIMT, and carotid plaque burden were significantly higher in individuals with DM. Analysis according to territory of cIMT measurement displayed substantial differences in left (DM: 1.32 +/- 0.78 mm vs. no DM: 1.20 +/- 0.66 mm, p = .04) and right carotid bulbs (DM: 1.33 +/- 0.82 mm vs. no DM: 1.18 +/- 0.69 mm, p = .02) with respect to DM status while nonsignificant variations were observed in left (DM: 0.98 +/- 0.49 mm vs. no DM: 0.91 +/- 0.35 mm, p = .06) and right common carotid artery (DM: 0.95 +/- 0.50 mm vs. no DM: 0.92 +/- 0.40 mm, p = .36). Conclusions: Diabetes mellitus is associated with increased cfPWV and cIMT, with more pronounced lesions in the carotid bulb. (c) 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved

The Role of Endothelial Related Circulating Biomarkers in COVID-19. A Systematic Review and Meta-analysis.

BACKGROUND: Several studies have revealed the link between Coronavirus Disease 2019 (COVID-19) and endothelial dysfunction. To better understand the global pattern of this relationship, we conducted a meta-analysis on endothelial biomarkers related to COVID-19 severity. METHODS: We systematically searched the literature up to March 10, 2021, for studies investigating the association between COVID-19 severity and the following endothelial biomarkers: Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), E-selectin, P-selectin, Von Willebrand Factor Antigen (VWF-Ag), soluble Thrombomodulin (sTM), Mid-regional pro-adrenomedullin (MR-proADM), and Angiopoietin-2 (Ang-2). Pooled estimates and mean differences (PMD) for each biomarker were reported. RESULTS: A total of 27 studies (n=2213 patients) were included. Critically ill patients presented with higher levels of MR-proADM (PMD: 0.71 nmol/L, 95% CI: 0.22 to 1.20 nmol/L, p=0.02), E-selectin (PMD: 13,32 pg/ml, 95% CI: 4,89 to 21,75 pg/ml, p=0.008), VCAM-1 (PMD: 479 ng/ml, 95% CI: 64 to 896 ng/ml, p=0.03), VWF-Ag (PMD: 110.5 IU/dl, 95% CI: 44.8 to 176.1 IU/dl, p=0.04) and Ang-2 (PMD: 2388 pg/ml, 95% CI: 1121 to 3655 pg/ml, p=0.003), as compared to non-critically ill ones. ICAM-1, P-selectin and thrombomodulin did not differ between the two groups (p>0.05). CONCLUSION: Endothelial biomarkers display significant heterogeneity in COVID-19 patients, with higher MR-proADM, E-selectin, VCAM-1, VWF-Ag, and Ang-2 levels being associated with increased severity. These findings strengthen the evidence on the key role of endothelial dysfunction in disease progress

Effects of Newer Antidiabetic Drugs on Endothelial Function and Arterial Stiffness: A Systematic Review and Meta-Analysis

Background. Newer antidiabetic drugs, i.e., dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may exert distinct cardiovascular effects. We sought to explore their impact on vascular function. Methods. Published literature was systematically searched up to January 2018 for clinical studies assessing the effects of DPP-4 inhibitors, GLP-1 RAs, and SGLT-2 inhibitors on endothelial function and arterial stiffness, assessed by flow-mediated dilation (FMD) of the brachial artery and pulse wave velocity (PWV), respectively. For each eligible study, we used the mean difference (MD) with 95% confidence intervals (CIs) for FMD and PWV. The pooled MD for FMD and PWV were calculated by using a random-effect model. The presence of heterogeneity among studies was evaluated by the I2 statistic. Results. A total of 26 eligible studies (n=668 patients) were included in the present meta-analysis. Among newer antidiabetic drugs, only SGLT-2 inhibitors significantly improved FMD (pooled MD 1.14%, 95% CI: 0.18 to 1.73, p=0.016), but not DPP-4 inhibitors (pooled MD = 0.86%, 95% CI: -0.15 to 1.86, p=0.095) or GLP-1 RA (pooled MD = 2.37%, 95% CI: -0.51 to 5.25, p=0.107). Both GLP-1 RA (pooled MD = −1.97, 95% CI: -2.65 to -1.30, p<0.001) and, to a lesser extent, DPP-4 inhibitors (pooled MD = -0.18, 95% CI: -0.30 to -0.07, p=0.002) significantly decreased PWV. Conclusions. Newer antidiabetic drugs differentially affect endothelial function and arterial stiffness, as assessed by FMD and PWV, respectively. These findings could explain the distinct effects of these drugs on cardiovascular risk of patients with type 2 diabetes

The association of air pollutants exposure with subclinical inflammation and carotid atherosclerosis

Background: Air pollution is a well-described environmental factor with evidence suggesting a firm association with cardiovascular diseases. The purpose of this study was to determine the association of exposure to gaseous air pollutants on atherosclerosis burden. Methods: 1955 inhabitants of the Corinthia region, aged 40 years or older, underwent clinical and biochemical assessment as well as carotid ultrasonography to evaluate carotid intima-media thickness (cIMT) and plaque burden. Analyzers recording time series concentration of CO, NO2, and SO2 were located at 4 different open sites (Regions 1, 2, 3 and 4) based on their proximity to industries, highways or shipyards. Results: A higher concentration of CO, NO2, and SO2 was observed in Region 4 compared to the other regions. Mean cIMT (Region 1: 0.93 +/- 0.24 mm; Region 2: 0.96 +/- 0.40 mm; Region 3: 0.94 +/- 0.39 mm; Region 4: 1.14 +/- 0.55 mm, p &lt; 0.001), maximum cIMT (p &lt; 0.001) as well as carotid plaque burden (Region 1: 13.3%; Region 2: 18.8%; Region 3: 22.4%; Region 4: 38.6%, p &lt; 0.001) were significantly higher in individuals of Region 4. Inhabitants of Region 4 had also higher levels of C reactive protein (Region 1: 4.56 +/- 4.85 mg/l; Region 2: 3.49 +/- 4.46 mg/l; Region 3: 4.03 +/- 3.32 mg/l, Region 4: 5.16 +/- 8.26 mg/l, p &lt; 0.001). Propensity score analysis revealed higher inter-area differences in mean cIMT of individuals with coronary artery disease (CAD) (high vs low air pollution area: 1.56 +/- 0.80 mm; vs. 1.18 +/- 0.54 mm, p &lt; 0.001) while there was no difference in cIMT of the matched population without CAD (p = 0.52). Conclusions: An increased carotid atherosclerotic and inflammatory burden is observed in inhabitants of areas with the highest concentration of air pollutants

H2020 ACCEPT project: D2.4 -ACCEPT system architecture description v2

This report presents the work carried out in Task 2.3 of ACCEPT regarding the system architecture design process and results up to the date of submission of the second version of the deliverable. In particular, the deliverable includes the high-level architecture model of the complete system, with the initial point being the design as presented in the Description of Work, and further refined and updated based on the work carried out in this period. This high-level architecture has also been mapped to the various SGAM layers to assist the future integration and development activities. The main bulk of the document concentrates on detailing the specifications and characteristics of the various system's software components. A dedicated template was created and circulated to all relevant partners in order to provide the components' functional and non-functional specifications, highlight interdependencies with other components, and declare the input/output data requirements (Annex I – Component’s Specifications and Requirements Template). Additionally, detailed component diagrams were created, and finally, the connection with Deliverable 2.1 (D2.1) was performed via a mapping of components to Use Cases that required relevant functionalities. Sequence diagrams were already created for D2.1 and are not presented here. A new section was created for the second version of the deliverable; it includes an update of the Use Cases, as described in D2.1, following necessary refinements and modifications that occurred in the course of the project. Similarly, the SGAM mapping, the component description and diagrams were updated to reflect the advances of the project. This is the second and final version of ACCEPT's system architecture. It will drive the development of the second and final iteration of the system and its constituent components. Following that, further refinements, if necessary, will be integrated in the new versions of the different components of the projec