Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Myelodysplastic/Myeloproliferative Neoplasms

The myelodysplastic syndrome-myeloproliferative neoplasms (MDS/MPNs) are a heterogeneous group of hematologic malignancies characterized by dysplastic and myeloproliferative clinical, laboratory, and morphological overlapping features, both in marrow and in blood

Layer-by-layer assembly for biofunctionalization of cellulosic fibers with emergent antimicrobial agents

Series title: Advances in polymer science series, ISSN 0065-3195, vol. 271Coating with polyelectrolyte multilayers has become a generic way to functionalize a variety of materials. In particular, the layer-by-layer (LbL) technique allows the coating of solid surfaces to give them several functionalities, including controlled release of bioactive agents. At present there are a large number of applications of the LbL technique; however, it is still little explored in the area of textiles. In this review we present an overview of LbL for textile materials made from synthetic or natural fibers. More specifically, LbL is presented as a method for obtaining new bioactive cotton (as in cellulosic fibers) for potential application in the medical field. We also review recent progress in the embedding of active agents in adsorbed multilayers as a novel way to provide the system with a “reservoir” where bioactive agents can be loaded for subsequent release.The authors would like to thank Fundação para a Ciência e Tecnologia (FCT) for the funding granted for the project PTDC/EBB-BIO/113671/2009 (FCOMP-01-0124-FEDER- 014752) Skin2Tex. Also, we would like to thank Fundo Europeu de Desenvolvimento Regional (FEDER) through COMPETE – Programa Operacional Factores de Competitividade (POFC) for co-funding