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.

Consideraciones morfológicas en el gentilicio. Un caso: Chile

This article analyzes the post-toponymic demonym from a morphological point of view. As is well known, because of its suffixal richness and of its derivational possibilities in Spanish, the morphological level is the most productive domain within the studies of post-toponymic demonyms. For this reason, we take up the taxonomic proposal of Ferreccio and Jocelin and work with an updated corpus (Kordic/Ferreccio), focusing on Chilean Spanish. Hence we present the most characteristic derivational aspects of the genetic process of the demonym, taking as operative unit the word and not the morpheme. We also stress some objections to the derivational mechanics and propose a typology of demonym and a classification of their polygenesis. The goal of this article is to show the many complexities in the creation of the post-toponymic demonyms, often subject to construction processes which go beyond pre-established rules.En el presente artículo analizamos el gentilicio postoponímico desde una perspectiva morfológica. Como se sabe, por su riqueza sufijal, así como por las posibilidades de derivación en lengua española, el nivel morfológico es el apartado más fructífero dentro de los estudios de los gentilicios postoponímicos. Por la misma razón retomamos una propuesta taxonómica (Ferreccio y Jocelin 1992) y trabajamos con un corpus actualizado (Kordic y Ferreccio 2014) centrándonos en el español de Chile. A partir de esto, presentamos los aspectos derivacionales más característicos del proceso genético del gentilicio; asimismo, destacamos algunos reparos en la mecánica derivacional, así como proponemos una tipología gentilicia y una clasificación de su poligénesis. La finalidad de este artículo será mostrar las complejidades en la constitución de los gentilicios postoponímicos, las más veces sujetos a procesos de construcción que van más allá de unas reglas preestablecidas

Consideraciones morfológicas en el gentilicio. Un caso: Chile

This article analyzes the post-toponymic demonym from a morphological point of view. As is well known, because of its suffixal richness and of its derivational possibilities in Spanish, the morphological level is the most productive domain within the studies of post-toponymic demonyms. For this reason, we take up the taxonomic proposal of Ferreccio and Jocelin and work with an updated corpus (Kordic/Ferreccio), focusing on Chilean Spanish. Hence we present the most characteristic derivational aspects of the genetic process of the demonym, taking as operative unit the word and not the morpheme. We also stress some objections to the derivational mechanics and propose a typology of demonym and a classification of their polygenesis. The goal of this article is to show the many complexities in the creation of the post-toponymic demonyms, often subject to construction processes which go beyond pre-established rules.En el presente artículo analizamos el gentilicio postoponímico desde una perspectiva morfológica. Como se sabe, por su riqueza sufijal, así como por las posibilidades de derivación en lengua española, el nivel morfológico es el apartado más fructífero dentro de los estudios de los gentilicios postoponímicos. Por la misma razón retomamos una propuesta taxonómica (Ferreccio y Jocelin 1992) y trabajamos con un corpus actualizado (Kordic y Ferreccio 2014) centrándonos en el español de Chile. A partir de esto, presentamos los aspectos derivacionales más característicos del proceso genético del gentilicio; asimismo, destacamos algunos reparos en la mecánica derivacional, así como proponemos una tipología gentilicia y una clasificación de su poligénesis. La finalidad de este artículo será mostrar las complejidades en la constitución de los gentilicios postoponímicos, las más veces sujetos a procesos de construcción que van más allá de unas reglas preestablecidas