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Letter by Acampa et al Regarding Article, “Underutilization of Ambulatory ECG Monitoring After Stroke and Transient Ischemic Attack: Missed Opportunities for Atrial Fibrillation Detection”
No full textPharmacogenetics of statins therapy
No full textCardiovascular disease has become the global leading cause of death worldwide, representing the most frequent cause of morbidity and mortality in the developed world. Statins, the most widely prescribed cholesterol-lowering drugs, are considered to be first-line therapeutics for the prevention of coronary heart disease and atherosclerosis. Meta-analyses from several primary and secondary intervention studies have clearly shown that cholesterol-lowering medication, significantly reduces cardiovascular events, mortality, and morbidity, but considerable interindividual variation exists in response to statin therapy. Pharmacogenomics can provide important insights into statins therapy through elucidation of the genetic (or genomic) contribution to variable response for these drugs. The search for genetic polymorphisms may enable us to identify novel determinants of drug responsiveness by means of the study of three candidate genes groups: (1) genes encoding proteins involved in metabolism or drug transport, or both, that influence drug pharmacokinetics; (2) genes encoding proteins involved in mechanism of action and/or metabolic pathways on which drugs operate (that influence pharmacodynamics); (3) genes encoding proteins involved in the underlying disease condition or intermediate phenotype. This review briefly summarizes the recent pharmacogenomic and pharmacogenetic patents and the potential contributions of genetic variations in candidate genes related to lipid and lipoprotein metabolism and statins efficacy. © 2007 Bentham Science Publishers Ltd
A critical assessment of the current pharmacotherapy for the treatment of embolic strokes of undetermined source
No full textIntroduction: 'Embolic stroke of undetermined source' (ESUS) is a term coined to identify non-lacunar stroke whose mechanism is likely to be embolic, and the source remains unidentified. The best antithrombotic treatment for preventing stroke recurrence in this population has not been delineated. Areas covered: The authors summarize and critically appraise the currently available evidence about the antithrombotic treatment for preventing stroke recurrence in patients with ESUS. Randomized trials addressing this topic were identified through MEDLINE (accessed by PubMed, as of November 2021, week 4). Expert opinion: Recent randomized trials have failed to demonstrate a significant benefit of direct oral anticoagulants over aspirin in reducing the recurrence of cerebral infarctions in unselected cohorts of patients with ESUS. The heterogeneity and often overlap of embolic sources may be possible explanations for the overall absence of a benefit of oral anticoagulants in ESUS as a single homogeneous entity. The results of these trials and their subgroup analyses have provided important cues to understand the pathophysiology of ESUS. They have, furthermore, increased in the interest in researchers in identifying distinct etiological phenotypes within this stroke population. There is a good rationale for ongoing and future investigations in order to tailor antithrombotic treatment according to individual features of patients with ESUS
How to Identify Patients at Risk of Silent Atrial Fibrillation after Cryptogenic Stroke: Potential Role of P Wave Dispersion
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Safety of intravenous thrombolysis in ischemic stroke caused by left atrial myxoma
No full textIntravenous thrombolytic treatment represents the gold standard for acute ischemic stroke treatment. However there is some concern to perform this treatment in patients with known cardiac myxomas for the risk of haemorragic complications. Here we described a 63-year-old patient with ischemic stroke due to embolization of atrial myxoma and treated with intravenous recombinant tissue plasminogen activator alteplase. The patient did not show improvement after treatment; 25 days later a brain CT showed an asymptomatic small hemorrhagic infarction, probably due to the large size of ischemic lesion. The lack of response might be explained by the embolization of a large tumor fragment. One-year after cardiac surgery clinical follow-up did not reveal new neurological signs nor symptoms. This case report suggests that systemic thrombolysis is a safe procedure also in patient with atrial myxoma. The efficacy of therapy seems to be related to embolus composition
Ischemic stroke after heart transplantation
No full textCerebrovascular complications after orthotopic heart transplantation (OHT) are more common in comparison with neurological sequelae subsequent to routine cardiac surgery. Ischemic stroke and transient ischemic attack (TIA) are more common (with an incidence of up to 13%) than intracranial hemorrhage (2.5%). Clinically, ischemic stroke is manifested by the appearance of focal neurologic deficits, although sometimes a stroke may be silent or manifests itself by the appearance of encephalopathy, reflecting a diffuse brain disorder. Ischemic stroke subtypes distribution in perioperative and postoperative period after OHT is very different from classical distribution, with different pathogenic mechanisms. Infact, ischemic stroke may be caused by less common and unusual mechanisms, linked to surgical procedures and to postoperative inflammation, peculiar to this group of patients. However, many strokes (40%) occur without a well-defined etiology (cryptogenic strokes). A silent atrial fibrillation (AF) may play a role in pathogenesis of these strokes and P wave dispersion may represent a predictor of AF. In OHT patients, P wave dispersion correlates with homocysteine plasma levels and hyperhomocysteinemia could play a role in the pathogenesis of these strokes with multiple mechanisms increasing the risk of AF. In conclusion, stroke after heart transplantation represents a complication with considerable impact not only on mortality but also on subsequent poor functional outcome
Spotlight on sirukumab for the treatment of rheumatoid arthritis: The evidence to date
Full text linkRheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease primarily affecting synovial joints and is characterized by persistent high-grade systemic inflammation. Proinflammatory cytokines, particularly interleukin-6 (IL-6), are of crucial importance in the pathogenesis of the disease, driving both joint inflammation and extra-articular comorbidities. Tocilizumab, a humanized IL-6 receptor-inhibiting monoclonal antibody, has been the first, and, to date, the only, IL-6 inhibitor approved for the treatment of RA. Many studies have demonstrated the potency and effectiveness of tocilizumab in controlling disease activity and radiological progression of RA. These successful results have encouraged the development of novel IL-6 inhibitors, among which a promising agent is sirukumab (SRK), a human anti-IL-6 monoclonal antibody currently under evaluation in Phase II/III studies in patients with RA, systemic lupus erythematosus, giant-cell arteritis, and major depressive disorder. The evidence to date indicates SRK as an effective and well-tolerated new therapeutic tool for patients with active RA, with some preliminary data suggesting a specific beneficial impact on relevant systemic complications associated with the disease, such as depression and cardiovascular disease. Conversely, although pathophysiological considerations make plausible the hypothesis that IL-6 blockade with SRK may also be beneficial in the treatment of many diseases other than RA (either autoimmune or not), available clinical data in patients with systemic lupus erythematosus do not seem to support this view, also giving rise to potentially relevant concerns about drug safety. If large Phase III clinical trials currently in progress in patients with RA confirm the efficacy and tolerability of SRK, then in the long term, this drug could, in the near future, occupy a place in the treatment of the disease, potentially also opening the doors to a more extended use of SRK in a wide range of disorders in which IL-6 plays a key pathogenic role. © 2016 Lazzerini et al
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