Circulation
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Randomized Controlled Trial Multicenter Study
Effects of interleukin-1β inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial.
To test formally the inflammatory hypothesis of atherothrombosis, an agent is needed that reduces inflammatory biomarkers such as C-reactive protein, interleukin-6, and fibrinogen but that does not have major effects on lipid pathways associated with disease progression. ⋯ Canakinumab, a human monoclonal antibody that neutralizes interleukin-1β, significantly reduces inflammation without major effect on low-density lipoprotein cholesterol or high-density lipoprotein cholesterol. These phase II trial data support the use of canakinumab as a potential therapeutic method to test directly the inflammatory hypothesis of atherosclerosis.
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Fetal long QT syndrome (LQTS) is associated with complex arrhythmias including torsades de pointes and 2° atrioventricular block. Sinus bradycardia has also been associated with fetal LQTS, but little is known of this rhythm manifestation. Our purpose was to characterize the fetal heart rate (FHR)/gestational age (GA) profile of fetal LQTS. ⋯ FHR varies by GA in both normal and LQTS fetuses. Postnatal evaluation of neonates with FHR ≤3(rd) percentile for GA may improve ascertainment of LQTS in fetuses, neonates, and undiagnosed family members.
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Tissue edema and endothelial barrier dysfunction as observed in sepsis and acute lung injury carry high morbidity and mortality, but currently lack specific therapy. In a recent case report, we described fast resolution of pulmonary edema on treatment with the tyrosine kinase inhibitor imatinib through an unknown mechanism. Here, we explored the effect of imatinib on endothelial barrier dysfunction and edema formation. ⋯ Thus, imatinib prevents endothelial barrier dysfunction and edema formation via inhibition of Arg. These findings identify imatinib as a promising approach to permeability edema and indicate Arg as novel target for edema treatment.