2022: the year in cardiovascular disease - the year of upfront lipid lowering combination therapy

Recent data clearly show that we are extremely ineffective in the use of lipid-lowering therapy (LLT). Furthermore, the problem seems to be the most serious in the group of patients at very high and extremely high-risk – the patients who stand to benefit most from effective therapy

Livelihood, locality and globalisation

Inaugural lecture Katholieke Universiteit Nijmege

Design and analysis of cross vaults along history

The history of cross vaults began almost 2,000 years ago with a widespread use during the Middle Ages and Renaissance, becoming nowadays one of the most diffused and fascinating structural typologies of the European building cultural heritage. However, conversely to the undeniable excellence achieved by the ancient masons, the structural behavior of these elements is still at the center of the scientific debate. In this regard, with the aim of reviewing the knowledge on this subject as a concise and valuable support for researchers involved in conservation of historical buildings, with a focus on design rules and structural analysis, the present study firstly introduces the cross vaults from a historical perspective, by describing the evolution of the main geometrical shapes together with basic practical rules used to size them. Then, the article deals with the subsequent advancements in structural analysis methods of vaults, until the development of modern limit analysis.This work was partially carried out under the program "Dipartimento di Protezione Civile - Consorzio RELUIS", signed on 2013-12-27.info:eu-repo/semantics/publishedVersio

Lipoprotein(a), the rediscovered risk factor, or how to get "back to the future".

International audienc

Diacerein reduces the excess synthesis of bone remodeling factors by human osteoblast cells from osteoarthritic subchondral bone.

International audienceAlthough cartilage degradation characterizes osteoarthritis (OA), there is evidence that remodeling of subchondral bone in this disease is a contributing factor. Therapeutic strategies to modify the metabolism of subchondral bone osteoblasts may be indicated to treat OA. We studied the effects of diacerein and rhein on the metabolic and inflammatory variables of OA subchondral osteoblasts.METHODS:Human OA primary subchondral osteoblast cells were used. The effect of diacerein and rhein at therapeutic concentrations (5-20 microg/ml) was determined by osteoblast phenotypic factors, alkaline phosphatase, osteocalcin, and cAMP; on metabolic agents urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and insulin-like growth factor-1 (IGF-1); and on inflammatory mediators interleukin 6 (IL-6), prostaglandin E2 (PGE2), and cyclooxygenase-2 (COX-2).RESULTS:Diacerein and rhein did not affect either basal and 1,25(OH)2D3 induced alkaline phosphatase or parathyroid hormone (PTH) stimulated cAMP formation. Conversely, they dose dependently and statistically inhibited 1,25(OH)2D3 induced osteocalcin release, a situation explained by a reduction of mRNA levels for osteocalcin. Of the metabolic factors, they inhibited the production of uPA, with rhein showing slightly more potency; inhibitions of 69% and 57% were reached at the highest concentration (20 microg/ml) of rhein and diacerein, respectively. Both drugs also inhibited the PAI-1 level, albeit at a much lower level than for uPA. Interestingly, determination of the uPA/PAI1 ratio revealed that both drugs inhibited it about 55%, suggesting a decrease in uPA activity. In contrast, IGF-1 levels only increased slightly when cells were treated with rhein but not with diacerein. A transient dose dependent effect was found on IL-6 production; an inhibition was noted at low drug concentrations, which returned to basal levels at the highest concentration tested. PGE2 levels increased exponentially and were related to a concomitant increase in COX-2 levels in response to both drugs.CONCLUSION:Our data indicate that diacerein and rhein do not appear to affect OA subchondral bone cells' basal cellular metabolism, yet both agents reveal a direct effect at reducing the synthetic activities of osteoblasts, which could be responsible for abnormal subchondral bone remodeling occurring during the course of OA

How to fill the GAPS-I in secondary prevention. Application of a strategy based on GLP1 analogues, antithrombotic agents, PCSK9 inhibitors, SGLT2 inhibitors and immunomodulators

The continuous progress in cardiovascular risk prevention strategies has led to an impressive reduction in mortality and recurrent ischemic events in patients with coronary artery disease (CAD). However, the control of several cardiovascular risk factors remains suboptimal in many CAD patients, with a high rate of recurrent events, underlying the need for more new prevention strategies. The GAPS-I (glucagon-like peptide 1 analogues, antithrombotic agents, proprotein convertase subtilisin/kexin type 9 inhibitors, sodium glucose cotransporter type 2 inhibitors and immunomodulators) strategy offers a promising potential in patients with a high-residual cardiovascular risk, who are frequently encountered in daily practice, by offering an individualized and structured approach to addressing their individual risk factors. The current review summarizes the evidence to date on each of its components, with respect to clinical outcomes and economic feasibility. The current evidence points to an efficacy of GAPS-I in reducing major adverse cardiovascular events and mortality, without a compromise on safety, albeit with the need for longer follow-up data