Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Evolution of the longitudinal and azimuthal structure of the near-side jet peak in Pb-Pb collisions at 1asNN = 2.76 TeV

In two-particle angular correlation measurements, jets give rise to a near-side peak, formed by particles associated to a higher-pT trigger particle. Measurements of these correlations as a function of pseudorapidity ( \u3b7) and azimuthal ( \u3c6) differences are used to extract the centrality and pT dependence of the shape of the near-side peak in the pT range 1 < pT < 8 GeV/c in Pb-Pb and pp collisions at 1asNN = 2.76 TeV. A combined fit of the near-side peak and long-range correlations is applied to the data and the peak shape is quantified by the variance of the distributions. While the width of the peak in the \u3c6 direction is almost independent of centrality, a significant broadening in the \u3b7 direction is found from peripheral to central collisions. This feature is prominent for the low-pT region and vanishes above 4 GeV/c. The widths measured in peripheral collisions are equal to those in pp collisions in the \u3c6 direction and above 3 GeV/c in the \u3b7 direction. Furthermore, for the 10% most central collisions and 1 < pT,assoc < 2 GeV/c, 1 < pT,trig < 3 GeV/c, a departure from a Gaussian shape is found: a depletion develops around the center of the peak. The results are compared to A Multi-Phase Transport (AMPT) model simulation as well as other theoretical calculations indicating that the broadening and the development of the depletion are connected to the strength of radial and longitudinal flow

Centrality dependence of inclusive J/\u3c8 production in p-Pb collisions at 1asNN = 5.02 TeV

We present a measurement of inclusive J/\u3c8 production in p-Pb collisions at 1asNN = 5.02TeV as a function of the centrality of the collision, as estimated from the energy deposited in the Zero Degree Calorimeters. The measurement is performed with the ALICE detector down to zero transverse momentum, pT, in the backward ( 124.46 < ycms < 122.96) and forward (2.03 < ycms < 3.53) rapidity intervals in the dimuon decay channel and in the mid-rapidity region ( 121.37 < ycms < 0.43) in the dielectron decay channel. The backward and forward rapidity intervals correspond to the Pb-going and p-going direction, respectively. The pT-differential J/\u3c8 production cross section at backward and forward rapidity is measured for several centrality classes, together with the corresponding average pT and pT2 values. The nuclear modification factor is presented as a function of centrality for the three rapidity intervals, and as a function of pT for several centrality classes at backward and forward rapidity. At mid- and forward rapidity, the J/\u3c8 yield is suppressed up to 40% compared to that in pp interactions scaled by the number of binary collisions. The degree of suppression increases towards central p-Pb collisions at forward rapidity, and with decreasing pT of the J/\u3c8. At backward rapidity, the nuclear modification factor is compatible with unity within the total uncertainties, with an increasing trend from peripheral to central p-Pb collisions

Centrality dependence of high-pT D meson suppression in Pb-Pb collisions at 1asNN = 2.76 TeV

The nuclear modification factor, RAA, of the prompt charmed mesons D0, D+ and D 17+, and their antiparticles, was measured with the ALICE detector in Pb-Pb collisions at a centre-of-mass energy 1asNN = 2.76 TeV in two transverse momentum intervals, 5 < pT < 8GeV/c and 8 < pT < 16GeV/c, and in six collision centrality classes. The RAA shows a maximum suppression of a factor of 5\u20136 in the 10% most central collisions. The suppression and its centrality dependence are compatible within uncertainties with those of charged pions. A comparison with the RAA of non-prompt J/\u3c8 from B meson decays, measured by the CMS Collaboration, hints at a larger suppression of D mesons in the most central collisions

Elliptic flow of identified hadrons in Pb-Pb collisions at 1asNN = 2.76 TeV

The elliptic flow coefficient (v2) of identified particles in Pb-Pb collisions at 1asNN = 2.76 TeV was measured with the ALICE detector at the Large Hadron Collider (LHC). The results were obtained with the Scalar Product method, a two-particle corre- lation technique, using a pseudo-rapidity gap of | 06\u3b7| > 0.9 between the identified hadron under study and the reference particles. The v2 is reported for \u3c0\ub1, K\ub1, K0S, p+p, \u3c6, \u39b+\u39b, \u39e 12+\u39e+ and \u3a9 12+\u3a9+ in several collision centralities. In the low transverse momentum (pT) region, pT 3 GeV/c

Search for long-lived particles decaying to leptons with large impact parameter in proton-proton collisions at root s=13 TeV

A search for new long-lived particles decaying to leptons using proton–proton collision data produced by the CERN LHC at s√=13TeV is presented. Events are selected with two leptons (an electron and a muon, two electrons, or two muons) that both have transverse impact parameter values between 0.01 and 10cm and are not required to form a common vertex. Data used for the analysis were collected with the CMS detector in 2016, 2017, and 2018, and correspond to an integrated luminosity of 118 (113)fb−1 in the ee channel (eμ and μμ channels). The search is designed to be sensitive to a wide range of models with displaced eμ, ee, and μμ final states. The results constrain several well-motivated models involving new long-lived particles that decay to displaced leptons. For some areas of the available phase space, these are the most stringent constraints to date

Measurement of prompt D-0 and D-0 meson azimuthal anisotropy and search for strong electric fields in PbPb collisions at root S-NN=5.02 TeV

SCOAP

Transverse Momentum Distribution and Nuclear Modification Factor of Charged Particles in p+Pb Collisions at sqrt[s_{NN}]=5.02\u2009\u2009TeV

The transverse momentum (pT) distribution of primary charged particles is measured in minimum bias (non-single-diffractive) p+Pb collisions at 1asNN=5.02 TeV with the ALICE detector at the LHC. The p T spectra measured near central rapidity in the range 0.5<p T<20 GeV/c exhibit a weak pseudorapidity dependence. The nuclear modification factor RpPb is consistent with unity for pT above 2 GeV/c. This measurement indicates that the strong suppression of hadron production at high pT observed in Pb+Pb collisions at the LHC is not due to an initial-state effect. The measurement is compared to theoretical calculations

Centrality dependence of \u3c0, K, and p production in Pb-Pb collisions at sqrt[s_{NN}]=2.76 TeV

In this paper measurements are presented of \u3c0\ub1, K\ub1, p, and p(bar) production at midrapidity (|y| < 0.5), in Pb-Pb collisions at 1asNN= 2.76 TeV as a function of centrality. The measurement covers the transverse-momentum (pT ) range from 100, 200, and 300 MeV/c up to 3, 3, and 4.6 GeV/c for \u3c0, K, and p, respectively. The measured pT distributions and yields are compared to expectations based on hydrodynamic, thermal and recombination models. The spectral shapes of central collisions show a stronger radial flow than measured at lower energies, which can be described in hydrodynamic models. In peripheral collisions, the pT distributions are not well reproduced by hydrodynamic models. Ratios of integrated particle yields are found to be nearly independent of centrality. The yield of protons normalized to pions is a factor 3c1.5 lower than the expectation from thermal models