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 <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >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 m2), 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

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Nuclear modification of Y states in pPb collisions at √SNN_{NN} = 5.02 TeV

Production cross sections of Υ(1S), Υ(2S), and Υ(3S) states decaying into μ+μ− in proton-lead (pPb) collisions are reported using data collected by the CMS experiment at √sNN = 5.02 TeV. A comparison is made with corresponding cross sections obtained with pp data measured at the same collision energy and scaled by the Pb nucleus mass number. The nuclear modification factor for Υ(1S) is found to be RpPb(Υ(1S)) = 0.806±0.024 (stat)±0.059 (syst). Similar results for the excited states indicate a sequential suppression pattern, such that RpPb(Υ(1S)) > RpPb(Υ(2S)) > RpPb(Υ(3S)). The suppression of all states is much less pronounced in pPb than in PbPb collisions, and independent of transverse momentum pΥT and center-of-mass rapidity yΥCM of the individual Υ state in the studied range p ΥT < 30 GeV/c and |yΥCM| <1.93. Models that incorporate final-state effects of bottomonia in pPb collisions are in better agreement with the data than those which only assume initial-state modifications

Constraints on the Initial State of Pb-Pb Collisions via Measurements of Z-Boson Yields and Azimuthal Anisotropy at root s(NN)=5.02 TeV

The CMS experiment at the LHC has measured the differential cross sections of Z bosons decaying to pairs of leptons, as functions of transverse momentum and rapidity, in lead-lead collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV. The measured Z boson elliptic azimuthal anisotropy coefficient is compatible with zero, showing that Z bosons do not experience significant final-state interactions in the medium produced in the collision. Yields of Z bosons are compared to Glauber model predictions and are found to deviate from these expectations in peripheral collisions, indicating the presence of initial collision geometry and centrality selection effects. The precision of the measurement allows, for the first time, for a data-driven determination of the nucleon-nucleon integrated luminosity as a function of lead-lead centrality, thereby eliminating the need for its estimation based on a Glauber model.Peer reviewe

Using Z boson events to study parton-medium interactions in Pb-Pb collisions

The spectra measurements of charged hadrons produced in the shower of a parton originating in the same hard scattering with a leptonically decaying Z boson are reported in lead-lead nuclei (Pb-Pb) and proton-proton (pp) collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV. Both Pb-Pb and pp data sets are recorded by the CMS experiment at the LHC and correspond to an integrated luminosity of 1.7  nb^{-1} and 320  pb^{-1}, respectively. Hadronic collision data with one reconstructed Z boson candidate with the transverse momentum p_{T}>30  GeV/c are analyzed. The Z boson constrains the initial energy and direction of the associated parton. In heavy ion events, azimuthal angular distributions of charged hadrons with respect to the direction of a Z boson are sensitive to modifications of the in-medium parton shower and medium response. compared to reference data from pp interactions, the results for central Pb-Pb collisions indicate a modification of the angular correlations. The measurements of the fragmentation functions and p_{T} spectra of charged particles in Z boson events, which are sensitive to medium modifications of the parton shower longitudinal structure, are also reported. Significant modifications in central Pb-Pb events compared to the pp reference data are also found for these observables

Electron and photon reconstruction and identification with the CMS experiment at the CERN LHC

The performance is presented of the reconstruction and identification algorithms for electrons and photons with the CMS experiment at the LHC. The reported results are based on proton-proton collision data collected at a center-of-mass energy of 13 TeV and recorded in 2016-2018, corresponding to an integrated luminosity of 136 fb(-1). Results obtained from lead-lead collision data collected at root S-NN = 5.02 TeV are also presented. Innovative techniques are used to reconstruct the electron and photon signals in the detector and to optimize the energy resolution. Events with electrons and photons in the final state are used to measure the energy resolution and energy scale uncertainty in the recorded events. The measured energy resolution for electrons produced in Z boson decays in proton-proton collision data ranges from 2 to 5%, depending on electron pseudorapidity and energy loss through bremsstrahlung in the detector material. The energy scale in the same range of energies is measured with an uncertainty smaller than 0.1 (0.3)% in the barrel (endcap) region in proton-proton collisions and better than 1(3)% in the barrel (endcap) region in heavy ion collisions. The timing resolution for electrons from Z boson decays with the full 2016-2018 proton-proton collision data set is measured to be 200 ps.Peer reviewe

Measurement of the top quark Yukawa coupling from tt ̄ kinematic distributions in the dilepton final state in proton-proton collisions at s=13 TeV

A measurement of the Higgs boson Yukawa coupling to the top quark is presented using proton-proton collision data at s=13 TeV, corresponding to an integrated luminosity of 137 fb-1, recorded with the CMS detector. The coupling strength with respect to the standard model value, Yt, is determined from kinematic distributions in tt ̄ final states containing ee, μμ, or eμ pairs. Variations of the Yukawa coupling strength lead to modified distributions for tt ̄ production. In particular, the distributions of the mass of the tt ̄ system and the rapidity difference of the top quark and antiquark are sensitive to the value of Yt. The measurement yields a best fit value of Yt=1.16-0.35+0.24, bounding Yt&lt;1.54 at a 95% confidence level

Measurements of production cross sections of WZ and same-sign WWboson pairs in association with two jets in proton-proton collisions at √s=13 TeV

Measurements of production cross sections of WZ and same-sign WW boson pairs in association with two jets in proton-proton collisions at s=13TeV at the LHC are reported. The data sample corresponds to an integrated luminosity of 137fb−1, collected with the CMS detector during 2016–2018. The measurements are performed in the leptonic decay modes [Formula presented] and [Formula presented], where ℓ,ℓ′=e, [Formula presented]. Differential fiducial cross sections as functions of the invariant masses of the jet and charged lepton pairs, as well as of the leading-lepton transverse momentum, are measured for W±W± production and are consistent with the standard model predictions. The dependence of differential cross sections on the invariant mass of the jet pair is also measured for WZ production. An observation of electroweak production of WZ boson pairs is reported with an observed (expected) significance of 6.8 (5.3) standard deviations. Constraints are obtained on the structure of quartic vector boson interactions in the framework of effective field theory

In-medium modification of dijets in PbPb collisions at √sNN = 5.02 TeV

Modifications to the distribution of charged particles with respect to high transverse momentum (pT) jets passing through a quark-gluon plasma are explored using the CMS detector. Back-to-back dijets are analyzed in lead-lead and proton-proton collisions at sNN = 5.02 TeV via correlations of charged particles in bins of relative pseudorapidity and angular distance from the leading and subleading jet axes. In comparing the lead-lead and proton-proton collision results, modifications to the charged-particle relative distance distribution and to the momentum distributions around the jet axis are found to depend on the dijet momentum balance xj , which is the ratio between the subleading and leading jet pT. For events with xj ≈ 1, these modifications are observed for both the leading and subleading jets. However, while subleading jets show significant modifications for events with a larger dijet momentum imbalance, much smaller modifications are found for the leading jets in these events. [Figure not available: see fulltext.

Measurements of (tt)over-barH Production and the CP Structure of the Yukawa Interaction between the Higgs Boson and Top Quark in the Diphoton Decay Channel

The first observation of the (tt) over barH process in a single Higgs boson decay channel with the full reconstruction of the final state (H -> gamma gamma) is presented, with a significance of 6.6 standard deviations (sigma). The CP structure of Higgs boson couplings to fermions is measured, resulting in an exclusion of the pure CP-odd structure of the top Yukawa coupling at 3.2 sigma. The measurements are based on a sample of protonproton collisions at a center-of-mass energy root s = 13 TeV collected by the CMS detector at the LHC, corresponding to an integrated luminosity of 137 fb(-1). The cross section times branching fraction of the (tt) over barH process is measured to be sigma B-(tt) over barH(gamma gamma) = 1.56(-0.32)(+0.34) th, which is compatible with the standard model prediction of 1.13(-0.11)(+0.08) fb. The fractional contribution of the CP-odd component is measured to be f(CP)(Hu) = 0.00 +/- 0.33.Peer reviewe