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.

Fraction of χc decays in prompt J/ψ production measured in pPb collisions at √sNN = 8.16 TeV

The fraction of χ c 1 and χ c 2 decays in the prompt J / ψ yield, F χ c → J / ψ = σ χ c → J / ψ / σ J / ψ , is measured by the LHCb detector in p Pb collisions at √ s NN = 8.16     TeV . The study covers the forward ( 1.5 < y ∗ < 4.0 ) and backward ( − 5.0 < y ∗ < − 2.5 ) rapidity regions, where y ∗ is the J / ψ rapidity in the nucleon-nucleon center-of-mass system. Forward and backward rapidity samples correspond to integrated luminosities of 13.6 ± 0.3 and 20.8 ± 0.5     nb − 1 , respectively. The result is presented as a function of the J / ψ transverse momentum p T , J / ψ in the range 1 < p T , J / ψ < 20     GeV / c . The F χ c → J / ψ fraction at forward rapidity is compatible with the LHCb measurement performed in p p collisions at √ s = 7     TeV , whereas the result at backward rapidity is 2.4 σ larger than in the forward region for 1 < p T , J / ψ < 3     GeV / c . The increase of F χ c → J / ψ at low p T , J / ψ at backward rapidity is compatible with the suppression of the ψ ( 2 S ) contribution to the prompt J / ψ yield. The lack of in-medium dissociation of χ c states observed in this study sets an upper limit of 180 MeV on the free energy available in these p Pb collisions to dissociate or inhibit charmonium state formation

Enhanced production of Λb0 baryons in high-multiplicity pp collisions at √s = 13 TeV

The production rate of Λ 0 b baryons relative to B 0 mesons in p p collisions at a center-of-mass energy √ s = 13     TeV is measured by the LHCb experiment. The ratio of Λ 0 b to B 0 production cross sections shows a significant dependence on both the transverse momentum and the measured charged-particle multiplicity. At low multiplicity, the ratio measured at LHCb is consistent with the value measured in e + e − collisions, and increases by a factor of ∼ 2 with increasing multiplicity. At relatively low transverse momentum, the ratio of Λ 0 b to B 0 cross sections is higher than what is measured in e + e − collisions, but converges with the e + e − ratio as the momentum increases. These results imply that the evolution of heavy b quarks into final-state hadrons is influenced by the density of the hadronic environment produced in the collision. Comparisons with several models and implications for the mechanisms enforcing quark confinement are discussed

Measurement of Λb0 , Λc+ , and Λ decay parameters using Λb0→Λc+h− decays

A comprehensive study of the angular distributions in the bottom-baryon decays Λ0 b → Λ c+h−(h = π, K), followed by Λþ c → Λhþ with Λ → pπ− or Λþ c → pK0 S decays, is performed using a data sample of proton-proton collisions corresponding to an integrated luminosity of 9 fb−1 collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. The decay parameters and the associated charge-parity (CP) asymmetries are measured, with no significant CP violation observed. For the first time, the Λ0 b → Λþ c h− decay parameters are measured. The most precise measurements of the decay parameters α, β, and γ are obtained for Λþ c decays and an independent measurement of the decay parameters for the strange-baryon Λ decay is provided. The results deepen our understanding of weak decay dynamics in baryon decays

Modification of χc1(3872) and ψ(2S) production in pPb collisions at √sNN = 8.16 TeV

The LHCb Collaboration measures production of the exotic hadron χc1(3872) in proton-nucleus collisions for the first time. Comparison with the charmonium state ψ(2S) suggests that the exotic χc1(3872) experiences different dynamics in the nuclear medium than conventional hadrons, and comparison with data from proton-proton collisions indicates that the presence of the nucleus may modify χc1(3872) production rates. This is the first measurement of the nuclear modification factor of an exotic hadron