European journal of internal medicine
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Eur. J. Intern. Med. · Jun 2020
ReviewAntisense lipoprotein[a] therapy: State-of-the-art and future perspectives.
Several lines of evidence now attest that lipoprotein[a] (Lp[a]) is a significant risk factor for many cardiovascular disorders. This enigmatic lipoprotein, composed of a single copy of apolipoprotein B (apoB) and apolipoprotein[a] (apo [a]), expresses peculiar metabolism, virtually independent from lifestyle interventions. Several therapeutic options have hence been proposed for lowering elevated Lp[a] values, with or without concomitant effect on low density lipoprotein (LDL) particles, mostly encompassing statins, ezetimibe, nicotinic acid, lipoprotein apheresis, and anti-PCSK9 monoclonal antibodies. ⋯ Preliminary evidence would suggest that apo[a] antisense therapy seems more appropriate in patients with isolated Lp[a] elevations, while apoB antisense therapy is perhaps more advisable in patients with isolated LDL elevations. In patients with concomitant elevations of Lp[a] and LDL, either combining the two apo[a] and apoB antisense therapies (a strategy which has never been tested), or the combination of well-known and relatively inexpensive drugs such as statins with antisense apo[a] inhibitors can be theoretically suggested. The results of an upcoming phase 3 study with antisense apo[a] inhibitors will hopefully provide definitive clues as to whether this approach may become the standard of care in patients with increased Lp[a] concentrations.
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Eur. J. Intern. Med. · Jun 2020
ReviewThe pivotal link between ACE2 deficiency and SARS-CoV-2 infection.
Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry into the cell of three strains of coronavirus: SARS-CoV, NL63 and SARS-CoV-2. ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type 2 pneumocytes and macrophages), kidney, testis and brain. ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a soluble form. ⋯ The additional ACE2 deficiency after viral invasion might amplify the dysregulation between the 'adverse' ACE→Angiotensin II→AT1 receptor axis and the 'protective' ACE2→Angiotensin1-7→Mas receptor axis. In the lungs, such dysregulation would favor the progression of inflammatory and thrombotic processes triggered by local angiotensin II hyperactivity unopposed by angiotensin1-7. In this setting, recombinant ACE2, angiotensin1-7 and angiotensin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection.
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Eur. J. Intern. Med. · Jun 2020
ReviewThe challenge of implementing Less is More medicine: A European perspective.
The concept of Less is More medicine emerged in North America in 2010. It aims to serve as an invitation to recognize the potential risks of overuse of medical care that may result in harm rather than in better health, tackling the erroneous assumption that more care is always better. In response, several medical societies across the world launched quality-driven campaigns ("Choosing Wisely") and published "top-five lists" of low-value medical interventions that should be used to help make wise decisions in each clinical domain, by engaging patients in conversations about unnecessary tests, treatments and procedures. ⋯ These also consist of a top-five list of actions: (1) a novel cultural approach starting from medical graduation courses, up to (2) patient and society education, (3) physician behavior change with data feedback, (4) communication training and (5) policy maker interventions. In contrast with the prevailing maximization of care, the optimization of care promoted by Less is More medicine can be an intellectual challenge but also a real opportunity to promote sustainable medicine. This project will constitute part of the future agenda of the European Federation of Internal Medicine.