A patent foramen ovale (PFO) has been shown to be highly prevalent in patients diagnosed with strokes of unknown cause, which are also called cryptogenic strokes (CSs). It has been a long-running controversy as to whether a PFO should be closed or not to prevent recurrent strokes in patients diagnosed with CS. A paradoxical embolism that is produced through a PFO is hypothesized to be a leading cause of CS, especially in younger patients with low risk factors for stroke. It remains controversial as to which anticoagulation therapy, defined as antithrombin or antiplatelet therapy, is better for patients with CS and a PFO. In addition, surgical and transcutaneous closure of a PFO has been proposed for the secondary prevention of stroke in patients with CS with PFO. Several randomized controlled trials have been conducted in recent years to test whether a PFO closure gives a significant benefit in the management of CS. Three earlier randomized controlled trials failed to show a statistically significant benefit for a PFO closure; thus, many investigators believed that a PFO was an incidental bystander in patients with CS. However, meta-analyses and more recent specific trials have eliminated several confounding factors and possible biases and have also emphasized the use of a shunt closure over medical therapy in patients with CS. Therefore, these latest studies (the CLOSE and REDUCE trials) can possibly change the treatment paradigm in the near future.
Approximately 40% of heart attack survivors remain at increased risk of recurrent cardiovascular events, despite the current treatment options showing that atherothrombosis is not exclusively a disorder of lipoprotein aggregation in the arterial wall. Clinical and experimental data suggest that inflammation plays an important role in atherothrombosis independent of the cholesterol level. Acute-phase reactants, such as C-reactive protein, increase in patients with coronary artery disease and are known to predict adverse outcomes in such patients. The recent CANTOS trial published in The New England Journal of Medicine provides evidence that interleukin-1β along with other cytokines play central roles in the inflammatory reaction that drives the interleukin-6 signaling pathway and have profound effects on cardiovascular outcomes. Several other ongoing studies are focused on multiple immune mediators involved in this process to support the inflammatory hypothesis of cardiovascular diseases. These new classes of drugs could represent the biggest breakthrough in cardiovascular medicine, which could have the greatest impact on cardiovascular mortality since the advent of statins. The drug canakinumab has shown promise in lowering atherosclerosis, and other drugs, such as colchicine and methotrexate, are gaining interest and are being investigated in multiple ongoing trials. A major concern is the affordability of these drugs, as most cardiovascular diseases are noted among people of lower socioeconomic statuses. The LoDoCo trial showed some benefits of colchicine, and whether this old drug can be marketed with a new label for cardiovascular disease remains in question. Therefore, a clear understanding of the different inflammatory pathways involved in atherosclerosis is needed to help develop more effective treatment modalities that will benefit humankind.
Patient presenting with fever, acute onset seizure and neck stiffness on examination; deteriorating despite initiation of early treatment for meningitis.
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