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.

New challenger for sustainable ethanol production in industrial biorefineries

Nations urgently need to tackle climate change in harmony with a circular economy to accomplish Sustainable Development Goals. Using sustainable biomass for sustainable industrial ethanol production seems attractive. Recently, the outstanding features of the arid plants nopales, aka prickly pear cactus, became headlines. Nopales outcompete algae and other biomasses in many aspects. Nopales are resilient, and climate change sparked their advancing invasion across European countries and other places. A sustainable biorefinery for ethanol production from nopales could holistically support promising outlooks on energy transition, water positive activities and food security near cities. However, the environmental impact and energy efficiency of this novel biorefinery for renewable energy under realistic scenarios is unknown. Traditional chemical pretreatments are polluters that can improve through environmental assessment and bio/chemical process design. We conducted experiments and assessments of scenarios for cleaner ethanol production from nopales in a biorefinery. Four scenarios considered two fertilisers, two pretreatments and two operational modes. We conducted life cycle assessment, energy balances and energy efficiency calculations. The most polluting scenario uses fossil fertilisers, acid hydrolysis and neutralization of nopal nutrients, and it resulted in approximately four times the global warming potential of the best scenario. Organic fertilisers and the use and reuse of ionic liquids with acetone for washing was the most ecofriendly scenario. We propose a cleaner design showing the lowest impacts in all categories, including Global Warming, Acidification and Eutrophication Potentials and more. Besides, the design used the lowest amount of energy per unit of energy as ethanol fuel. It also has the best energy efficiency since it converted three-fold the amount of spent energy, in the worst scenario, into net energy as ethanol fuel. Sustainable biorefineries and sustainable biomasses are opportunities in the circular economy while pursuing climate risk mitigation, carbon neutrality and green energy for sustainable development

Hydrodynamic performance evaluation of continuous stirred-tank anaerobic reactor model using CFD

International audienceIn this paper, a computational fluid dynamics (CFD) model that evaluates recirculating mixing in a laboratory scale flat bottom anaerobic reactor was developed. Rheological properties of fluid were included in this model to investigate their influence on performance in steady state. The digest fluid was rheologically characterized. A non-Newtonian behavior was observed, which can be adjusted according to power law model. In this case a single phase model of Newtonian fluid was used as reference to illustrate the non-Newtonian impact on flow patterns. In the comparison, the flow rates and effective viscosity were used in different planes and heights of digester. Dead zones were determined according to the effective viscosity because it depends on shear rate. It was found that using non-Newtonian fluid, velocity recirculations are greater than those generated by Newtonian fluid and have different directions. Furthermore, effective viscosity reduces through digester when non-Newtonian fluid is used. Analyzing different flow rates for input and using CFD model with rheological properties of fluid, made it possible to reduce dead zones