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

Acral and multicentric pigmented Bowen's disease in HIV-Positive patients: Report on two unusual cases

In situ squamous cell carcinoma of the skin (SCCis or Bowen's disease) is a common intraepidermal cutaneous malignancy with a low invasive potential. Acral Bowen's disease is usually solitary, but multiple acral SCCis have been reported. Pigmented Bowen's disease is typically unilesional and characterized by a hyperpigmented plaque with a velvety of keratotic surface, which can eventually simulate melanoma clinically. We describe two HIV-positive patients who presented with multiple pigmented SCCis involving the distal extremities. In patients with immunosuppression, the presence of multiple and hyperpigmented verrucae that clinically do not respond to adequate treatment should raise the differential diagnosis of SCC in situ

International Nosocomial Infection Control Consortium report, data summary of 50 countries for 2010-2015: Device-associated module

•We report INICC device-associated module data of 50 countries from 2010-2015.•We collected prospective data from 861,284 patients in 703 ICUs for 3,506,562 days.•DA-HAI rates and bacterial resistance were higher in the INICC ICUs than in CDC-NHSN's.•Device utilization ratio in the INICC ICUs was similar to CDC-NHSN's. Background: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2010-December 2015 in 703 intensive care units (ICUs) in Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific. Methods: During the 6-year study period, using Centers for Disease Control and Prevention National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 861,284 patients hospitalized in INICC hospital ICUs for an aggregate of 3,506,562 days. Results: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the INICC medical-surgical ICUs, the pooled rate of central line-associated bloodstream infection, 4.1 per 1,000 central line-days, was nearly 5-fold higher than the 0.8 per 1,000 central line-days reported from comparable US ICUs, the overall rate of ventilator-associated pneumonia was also higher, 13.1 versus 0.9 per 1,000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 5.07 versus 1.7 per 1,000 catheter-days. From blood cultures samples, frequencies of resistance of Pseudomonas isolates to amikacin (29.87% vs 10%) and to imipenem (44.3% vs 26.1%), and of Klebsiella pneumoniae isolates to ceftazidime (73.2% vs 28.8%) and to imipenem (43.27% vs 12.8%) were also higher in the INICC ICUs compared with CDC-NHSN ICUs. Conclusions: Although DA-HAIs in INICC ICU patients continue to be higher than the rates reported in CDC-NSHN ICUs representing the developed world, we have observed a significant trend toward the reduction of DA-HAI rates in INICC ICUs as shown in each international report. It is INICC's main goal to continue facilitating education, training, and basic and cost-effective tools and resources, such as standardized forms and an online platform, to tackle this problem effectively and systematically

Measurement of the Cross Sections of Ξc0\Xi^0_{c} and Ξc+\Xi^+_{c} Baryons and of the Branching-Fraction Ratio BR(Ξc0→Ξ−e+νe\Xi^0_{c} \rightarrow \Xi^-{e}^+\nu_{ e})/BR(Ξc0→Ξ−π+\Xi^0_{c} \rightarrow \Xi^-\pi^+) in pp collisions at 13 TeV

The $p_T$-differential cross sections of prompt charm-strange baryons Ξ$_c^0$ and Ξ$_c^+$ were measured at midrapidity (|y|<0.5) in proton-proton (pp) collisions at a center-of-mass energy $\sqrt{s}$ = 13 TeV with the ALICE detector at the LHC. The Ξ$_c^0$ baryon was reconstructed via both the semileptonic decay (Ξ$^-$e$^+$ν$_e$) and the hadronic decay (Ξ$^-$π$^+$) channels. The Ξ$_c^+$ baryon was reconstructed via the hadronic decay (Ξ$^-$π$^+$π$^+$) channel. The branching-fraction ratio BR(Ξ$_c^0$→Ξ$^-$e$^+$ν$_e$)/BR(Ξ$_c^0$→Ξ$^-$π$^+$) = 1.38±0.14(stat)±0.22(syst) was measured with a total uncertainty reduced by a factor of about 3 with respect to the current world average reported by the Particle Data Group. The transverse momentum ($p_T$) dependence of the Ξ$_c^0-$ and Ξ$_c^+$-baryon production relative to the D$^0$ meson and to the Σ$_c^{0,+,++}$- and Λ$_c^+$-baryon production are reported. The baryon-to-meson ratio increases toward low $p_T$ up to a value of approximately 0.3. The measurements are compared with various models that take different hadronization mechanisms into consideration. The results provide stringent constraints to these theoretical calculations and additional evidence that different processes are involved in charm hadronization in electron-positron (e$^+$e$^-$) and hadronic collisions

Nuclear modification factor of light neutral-meson spectra up to high transverse momentum in p–Pb collisions at sNN=8.16 TeV

International audienceNeutral pion (π0) and η meson production cross sections were measured up to unprecedentedly high transverse momenta (pT) in p–Pb collisions at sNN=8.16TeV. The mesons were reconstructed via their two-photon decay channel in the rapidity interval −1.3&lt;y&lt;0.3 in the ranges of 0.4&lt;pT&lt;200 GeV/c and 1.0&lt;pT&lt;50 GeV/c, respectively. The respective nuclear modification factor (RpPb) is presented for pT up to of 200 and 30 GeV/c, where the former was achieved by extending the π0 measurement in pp collisions at s=8TeV using the merged cluster technique. The values of RpPb are below unity for pT&lt;10 GeV/c, while they are consistent with unity for pT&gt;10 GeV/c, leaving essentially no room for final state energy loss. The new data provide strong constraints for nuclear parton distribution and fragmentation functions over a broad kinematic range and are compared to model predictions as well as previous results at sNN=5.02TeV

Measurement of K∗^{*}(892)±^{\mathrm{\pm}} production in inelastic pp collisions at the LHC

International audienceThe first results on K⁎(892)± resonance production in inelastic pp collisions at LHC energies of s=5.02, 8, and 13 TeV are presented. The K⁎(892)± has been reconstructed via its hadronic decay channel K⁎(892)→±KS0+π± with the ALICE detector. Measurements of transverse momentum distributions, pT-integrated yields, and mean transverse momenta for charged K⁎(892) are found to be consistent with previous ALICE measurements for neutral K⁎(892) within uncertainties. For pT&gt;1 GeV/c the K⁎(892)± transverse momentum spectra become harder with increasing centre-of-mass energy from 5.02 to 13 TeV, similar to what previously observed for charged kaons and pions. For pT&lt;1 GeV/c the K⁎(892)± yield does not evolve significantly and the abundance of K⁎(892)± relative to K is rather independent of the collision energy. The transverse momentum spectra, measured for K⁎(892)± at midrapidity in the interval 0 &lt;pT&lt;15 GeV/c, are not well described by predictions of different versions of PYTHIA 6, PYTHIA 8 and EPOS-LHC event generators. These generators reproduce the measured pT-integrated K⁎±/K ratios and describe well the momentum dependence for pT&lt;2 GeV/c

Charged-particle multiplicity fluctuations in Pb–Pb collisions at √ sNN = 2.76 TeV

Measurements of event-by-event fluctuations of charged-particle multiplicities in Pb–Pb collisionsat √sNN = 2.76 TeV using the ALICE detector at the CERN Large Hadron Collider (LHC) are presented in the pseudorapidity range |η| < 0.8 and transverse momentum 0.2 < pT < 2.0 GeV/c. The amplitude of the fluctuations is expressed in terms of the variance normalized by the mean of the multiplicity distribution. The η and pT dependences of the fluctuations and their evolution with respect to collision centrality are investigated. The multiplicity fluctuations tend to decrease from peripheral to central collisions. The results are compared to those obtained from HIJING and AMPT Monte Carlo event generators as well as to experimental data at lower collision energies. Additionally, the measured multiplicity fluctuations are discussed in the context of the isothermal compressibility of the high-density strongly-interacting system formed in central Pb–Pb collisions

Experimental Evidence for an Attractive p-ϕ\phi Interaction

This Letter presents the first experimental evidence of the attractive strong interaction between a proton and a ϕ meson. The result is obtained from two-particle correlations of combined $p$-ϕ⊕ $\bar{p}$-ϕ pairs measured in high-multiplicity pp collisions at $\sqrt{s}$ = 13 TeV by the ALICE Collaboration. The spin-averaged scattering length and effective range of the p-ϕ interaction are extracted from the fully corrected correlation function employing the Lednický-Lyuboshits approach. In particular, the imaginary part of the scattering length vanishes within uncertainties, indicating that inelastic processes do not play a prominent role for the p-ϕ interaction. These data demonstrate that the interaction is dominated by elastic p-ϕ scattering. Furthermore, an analysis employing phenomenological Gaussian- and Yukawa-type potentials is conducted. Under the assumption of the latter, the N-ϕ coupling constant is found to be $g_{N-ϕ}$ = 0.14 ± 0.03(stat) ± 0.02(syst). This work provides valuable experimental input to accomplish a self-consistent description of the N-ϕ interaction, which is particularly relevant for the more fundamental studies on partial restoration of chiral symmetry in nuclear medium

Kaon–proton strong interaction at low relative momentum via femtoscopy in Pb–Pb collisions at the LHC

In quantum scattering processes between two particles, aspects characterizing the strong and Coulomb forces can be observed in kinematic distributions of the particle pairs. The sensitivity to the interaction potential reaches a maximum at low relative momentum and vanishing distance between the two particles. Ultrarelativistic heavy-ion collisions at the LHC provide an abundant source of many hadron species and can be employed as a measurement method of scattering parameters that is complementary to scattering experiments. This study confirms that momentum correlations of particles produced in Pb–Pb collisions at the LHC provide an accurate measurement of kaon–proton scattering parameters at low relative momentum, allowing precise access to the $K^- p \to K^- p$ process. This work also validates the femtoscopic measurement in ultrarelativistic heavy-ion collisions as an alternative to scattering experiments and a complementary tool to the study of exotic atoms with comparable precision. In this work, the first femtoscopic measurement of momentum correlations of $K^- p(K^- \overline{p})$ and $K^+p(K^-\overline{p})$ pairs in Pb–Pb collisions at centre-of-mass energy per nucleon pair of $\sqrt{s_{NN}}$=5.02 TeV registered by the ALICE experiment is reported. The components of the $K^-p$ complex scattering length are extracted and found to be $\Re f_0=-0.91 \pm 0.03 \textrm{(stat)}^{+0.17}_{-0.03} \textrm{(syst)}$ and $\Im f_0=0.92 \pm 0.05 \textrm{(stat)}_{-0.33}^{+0.12} \textrm{(syst)}$. The results are compared with chiral effective field theory predictions as well as with existing data from dedicated scattering and exotic kaonic atom experiments