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.

Efecto del extracto de puerro (Allium porrum L.) sobre la supervivencia de esclerocios de Sclerotium cepivorum

La utilización de estimulantes de la germinación de los esclerocios de Sclerotium cepivorum, colocados antes de la implantación del cultivo, son una alternativa de manejo de la enfermedad. Se evaluó el efecto de un extracto de puerro (Alliumporrum L.) sobre la supervivencia de los esclerocios del patógeno. Extracto de puerro fue colocado en cajas de Petri con 50 esclerocios, mezclados con 10 g de suelo, a las concentraciones 50, 75 y 100% (extracto en agua). Se determinó la eficiencia sobre la germinación de los esclerocios y la viabilidad de los recuperados,no germinados, ambos a los 30 y 60 días. El extracto de puerro disminuyó el porcentaje de esclerocios recuperados. Con extracto al 100% y 75% germinaron un 32-38,5% y 31,5-35,5%, respectivamente, de los esclerocios en los dos tiempos evaluados, y valores menores se encontraron con extracto al 50%.La viabilidad de los esclerocios recuperados disminuyó entre 66,5 y 54,5%, para el extracto al 100%, y entre 68,5% y 51,5% para el extracto al 75%, a los 30 y 60 días, respectivamente. La supervivencia de los esclerocios disminuyó por la estimulación de la germinación y por la pérdida de viabilidad luego de aplicados los extractos

Efecto del extracto de puerro (Allium porrum L.) sobre la supervivencia de esclerocios de Sclerotium cepivorum Effect of leek extract (Allium porrum L.) on the survival of sclerotia of Sclerotium cepivorum

La utilización de estimulantes de la germinación de los esclerocios de Sclerotium cepivorum, colocados antes de la implantación del cultivo, son una alternativa de manejo de la enfermedad. Se evaluó el efecto de un extracto de puerro (Allium porrum L.) sobre la supervivencia de los esclerocios del patógeno. Extracto de puerro fue colocado en cajas de Petri con 50 esclerocios, mezclados con 10 g de suelo, a las concentraciones 50, 75 y 100% (extracto en agua). Se determinó la eficiencia sobre la germinación de los esclerocios y la viabilidad de los recuperados, no germinados, ambos a los 30 y 60 días. El extracto de puerro disminuyó el porcentaje de esclerocios recuperados. Con extracto al 100% y 75% germinaron un 32-38,5% y 31,5-35,5%, respectivamente, de los esclerocios en los dos tiempos evaluados, y valores menores se encontraron con extracto al 50%. La viabilidad de los esclerocios recuperados disminuyó entre 66,5 y 54,5%, para el extracto al 100%, y entre 68,5% y 51,5% para el extracto al 75%, a los 30 y 60 días, respectivamente. La supervivencia de los esclerocios disminuyó por la estimulación de la germinación y por la pérdida de viabilidad luego de aplicados los extractos.<br>The use of sclerotial germination stimulants of Sclerotium cepivorum prior to crop planting is an alternative for the management of the disease. In the present work, we evaluated the effect of leek extract (Allium porrum L.) on the survival of sclerotia of S. cepivorum. Aqueous leek extract at concentrations of 50, 75 and 100% were placed in Petri dishes containing 50 sclerotia mixed with 10 g soil. Both the efficacy of the extract on sclerotia germination and the viability of recovered ungerminated sclerotia were determined after 30 and 60 days. Leek extract reduced the percentage of recovered sclerotia in all cases. Percentages of germinated sclerotia ranged from 32 to 38.5% and from 31.5% to 35.5% at 100% and 75% extract concentration respectively, at each of the two times studied. Lower values were obtained at 50% extract concentration. Viability of recovered sclerotia decreased between 66.5 and 54.5% at 100% extract concentrations and between 68.5 and 51.5% at 75% extract concentrations after 30 and 60 days, respectively. Sclerotial pathogen survival decreased by the germination stimulation and by the loss of viability after the application of the extracts

Estimación de curvas de progreso de la incidencia de podredumbre blanca (Sclerotium cepivorum Berk.) en cultivos de ajo mediante un modelo no lineal mixto

En este trabajo se modela la curva de progreso de la podredumbre blanca en cultivos de ajo, mediante modelos no lineales mixtos que contemplan el efecto de factores concomitantes en el desarrollo de las epidemias. Entre 2001 y 2003 en Cruz del Eje y Jesús María, Argentina, se evaluaron la densidad inicial de esclerocios (DIE) y la incidencia de la enfermedad quincenalmente hasta cosecha. Con DIE alta (&gt;15 esclerocios/100 g de suelo) la incidencia final fue alta (64-100%) y con DIE baja (?15 esclerocios/100 g de suelo) varió entre 0-100%. El modelo logístico mixto seleccionado tuvo “interceptos” y pendientes aleatorias y diferentes para cada combinación de “ambiente” (localidad y año) y categoría de DIE (altas y bajas). La representación de las curvas epidémicas se hizo mediante tres curvas específicas de sitio, la típica con efecto aleatorio cero, que expresa la forma general del modelo y  las percentiles Q1 (0,25) y Q3 (0,75) que expresan la variabilidad.  La variabilidad de los “interceptos” y pendientes dependió solamente de la DIE, y fue menor en los “interceptos” con DIE “altas” que en aquellos con DIE “bajas”;en las pendientes se observó el efecto opuesto

Rivaroxaban with or without aspirin in stable cardiovascular disease

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events

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. Copyright © 2017 Massachusetts Medical Society