Cardiovascular risk in patients with and without diabetes presenting with chronic coronary syndrome in 2004-2016

BACKGROUND: It was recently shown that new-onset diabetes patients without previous cardiovascular disease have experienced a markedly reduced risk of adverse cardiovascular events from 1996 to 2011. However, it remains unknown if similar improvements are present following the diagnosis of chronic coronary syndrome. The purpose of this study was to examine the change in cardiovascular risk among diabetes patients with chronic coronary syndrome from 2004 to 2016. METHODS: We included patients with documentation of coronary artery disease by coronary angiography between 2004 and 2016 in Western Denmark. Patients were stratified by year of index coronary angiography (2004–2006, 2007–2009, 2010–2012, and 2013–2016) and followed for two years. The main outcome was major adverse cardiovascular events (MACE) defined as myocardial infarction, ischemic stroke, or death. Analyses were performed separately in patients with and without diabetes. We estimated two-year risk of each outcome and adjusted incidence rate ratios (aIRR) using patients examined in 2004-2006 as reference. RESULTS: Among 5931 patients with diabetes, two-year MACE risks were 8.4% in 2004–2006, 8.5% in 2007–2009, and then decreased to 6.2% in 2010–2012 and 6.7% in 2013–2016 (2013–2016 vs 2004–2006: aIRR 0.70, 95% CI 0.53–0.93). In comparison, 23,540 patients without diabetes had event rates of 6.3%, 5.2%, 4.2%, and 3.9% for the study intervals (2013–2016 vs 2004–2006: aIRR 0.57, 95% CI 0.48–0.68). CONCLUSIONS: Between 2004 and 2016, the two-year relative risk of MACE decreased by 30% in patients with diabetes and chronic coronary syndrome, but slightly larger absolute and relative reductions were observed in patients without diabetes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-021-02312-y

Implementation of the EU CCS Directive in Europe: results and development in 2013

Directive 2009/31/EC of the European Parliament on the geological storage of carbon dioxide, entered into force on June 25th 2009. By the end 2013 the CCS Directive has been fully transposed into national law to the satisfaction of the EC in 20 out of 28 EU Member States, while six EU countries (Austria, Cyprus, Hungary, Ireland, Sweden and Slovenia) had to complete transposing measures. In July 2014 the European Commission closed infringement procedures against Cyprus, Hungary and Ireland, which have notified the EC that they have taken measures to incorporate the CCS Directive into national law. Among other three countries Sweden has updated its legislation and published a new law in their country in March 2014, permitting CO2 storage offshore. The evaluation of the national laws in Poland, which were accepted at national level in November 2013, and Croatia, which entered the EU on 7 July 2013 and simultaneously transposed the CCS directive, is still ongoing in 2014. The first storage permit under the Directive (for the ROAD Project in the offshore Netherlands) has been approved by the EC. While CO2 storage is permitted in a number of European countries, temporary restrictions were applied in Czech Republic, Denmark and Poland. CO2 storage is prohibited except for research and development in Estonia, Finland, Luxembourg, two regions in Belgium and Slovenia due to their geological conditions, but also forbidden in Austraia, Ireland and Latvia. The size of exploration areas for CO2 storage sites is limited in Bulgaria and Hungary. In Germany, only limited CO2 storage will be permitted until 2018 (up to 4 Mt CO2 annually)

CCS Directive Transposition into National Laws in Europe: Progress and Problems by the End of 2011

AbstractThe EU CCS Directive transposition process and related issues in 26 European countries, comprising 24 EU member states, Norway and Croatia were studied in the EU FP7 project: “CGS Europe” in 2011–2012. By the end of 2011 the transposition of the Directive into national law had been approved by the European Commission (EC) in Spain only, but had been approved at national/jurisdictional level in 12 other countries (Austria, Denmark, Estonia, France, Greece, Ireland, Italy, Latvia, Lithuania, the Netherlands, Slovakia and Sweden) and two regions of Belgium. By January 2012, the European Commission had assessed and approved national submissions of CCS legal acts transposing the Directive in Denmark, France, Italy, Lithuania, Malta, the Netherlands and Slovenia. Implementation in the UK was completed in February 2012 and by end March 2012, implementation at national level was also complete in Bulgaria, Czech Republic, Portugal and Romania.Belgium, Croatia, Finland, Germany, Hungary, Norway and Poland had not finished the transposition of the CCS Directive by end March 2012. The process had been complicated by ongoing political debates in Norway, public opposition in Germany and ministerial elections in Poland. More than 20 operating, developing and planned CCS pilot and demonstration projects have been identified in nine European countries. Storage capacity was estimated by CGS Europe project partners as “sufficient at national level” in 17 countries

Modulation of P2X3 and P2X2/3 Receptors by Monoclonal Antibodies*

Purinergic homomeric P2X3 and heteromeric P2X2/3 receptors are ligand-gated cation channels activated by ATP. Both receptors are predominantly expressed in nociceptive sensory neurons, and an increase in extracellular ATP concentration under pathological conditions, such as tissue damage or visceral distension, induces channel opening, membrane depolarization, and initiation of pain signaling. Hence, these receptors are considered important therapeutic targets for pain management, and development of selective antagonists is currently progressing. To advance the search for novel analgesics, we have generated a panel of monoclonal antibodies directed against human P2X3 (hP2X3). We have found that these antibodies produce distinct functional effects, depending on the homomeric or heteromeric composition of the target, its kinetic state, and the duration of antibody exposure. The most potent antibody, 12D4, showed an estimated IC50 of 16 nm on hP2X3 after short term exposure (up to 18 min), binding to the inactivated state of the channel to inhibit activity. By contrast, with the same short term application, 12D4 potentiated the slow inactivating current mediated by the heteromeric hP2X2/3 channel. Extending the duration of exposure to ∼20 h resulted in a profound inhibition of both homomeric hP2X3 and heteromeric hP2X2/3 receptors, an effect mediated by efficient antibody-induced internalization of the channel from the plasma membrane. The therapeutic potential of mAb12D4 was assessed in the formalin, complete Freund's adjuvant, and visceral pain models. The efficacy of 12D4 in the visceral hypersensitivity model indicates that antibodies against P2X3 may have therapeutic potential in visceral pain indications