Acute Kidney Injury After Percutaneous Coronary Intervention Guided by Intravascular Ultrasound

Purpose We investigated the impact of intravascular ultrasound guidance on reducing the incidence of contrast-induced acute kidney injury (CI-AKI) in patients undergoing percutaneous coronary intervention (PCI). Methods Ninety-nine patients were enrolled in this prospective cohort who were not randomly assigned to angiography-guided percutaneous coronary intervention or intravascular ultrasound-guided percutaneous coronary intervention. The patients were hospitalized at the Vietnam National Heart Institute - Bach Mai Hospital between 2019 and 2020. Acute kidney injury incidence during hospitalization was the primary endpoint. Results A total of 99 patients were divided into two groups: the intravascular ultrasound-guided group (33 participants) and the angiography-guided group (66 participants). The mean ± SD contrast volume of each group was 95.2 ± 37.1 mL and 133.0 ± 36.0 mL for the ultrasound-guided and angiography-guided groups, with P \u3c 0.0001. Intravascular imaging-guided percutaneous coronary intervention (IVUS-guided PCI) was associated with reduced acute kidney injury incidence during hospitalization: 0.0% vs. 12.12% and P = 0.049. Conclusions Intravascular ultrasound is a safe imaging tool that guides percutaneous coronary intervention and significantly reduces the rate of acute kidney injury compared to angiography alone. Patients who have a high chance of experiencing acute kidney injury benefit from using intravascular ultrasound

Pharmacokinetics and Pharmacodynamics of Once-Daily versus Twice-Daily Raltegravir in Treatment-Naïve HIV-Infected Patients

ABSTRACT QDMRK was a phase III clinical trial of raltegravir given once daily (QD) (800-mg dose) versus twice daily (BID) (400 mg per dose), each in combination with once-daily coformulated tenofovir-emtricitabine, in treatment-naive HIV-infected patients. Pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) analyses were conducted using a 2-step approach: individual non-model-based PK parameters from observed sparse concentration data were determined, followed by statistical analysis of potential relationships between PK and efficacy response parameters after 48 weeks of treatment. Sparse PK sampling was performed for all patients (QD, n = 380; BID, n = 384); selected sites performed an intensive PK evaluation at week 4 (QD, n = 22; BID, n = 20). In the intensive PK subgroup, daily exposures (area under the concentration-time curve from 0 to 24 h [AUC 0–24 ]) were similar between the two regimens, but patients on 800 mg QD experienced ∼4-fold-higher maximum drug concentration in plasma ( C max ) values and ∼6-fold-lower trough drug concentration ( C trough ) values than those on 400 mg BID. Geometric mean (GM) C trough values were similarly lower in the sparse PK analysis. With BID dosing, there was no indication of any significant PK/PD association over the range of tested PK parameters. With QD dosing, C trough values correlated with the likelihood of virologic response. Failure to achieve an HIV RNA level of <50 copies/ml appeared predominantly at high baseline HIV RNA levels in both treatment arms and was associated with lower values of GM C trough in the 800-mg-QD arm, though other possible drivers of efficacy, such as time above a threshold concentration, could not be evaluated due to the sparse sampling scheme. Together, these findings emphasize the importance of the shape of the plasma concentration-versus-time curve for long-term efficacy

Efficacy and safety of raltegravir for treatment of HIV for 5 years in the BENCHMRK studies: Final results of two randomised, placebo-controlled trials

BACKGROUND: Two randomised, placebo-controlled trials-BENCHMRK-1 and BENCHMRK-2-investigated the efficacy and safety of raltegravir, an HIV-1 integrase strand-transfer inhibitor. We report final results of BENCHMRK-1 and BENCHMRK-2 combined at 3 years (the end of the double-blind phase) and 5 years (the end of the study). METHODS: Integrase-inhibitor-naive patients with HIV resistant to three classes of drug and who were failing antiretroviral therapy were enrolled. Patients were randomly assigned (2:1) to raltegravir 400 mg twice daily or placebo, both with optimised background treatment. Patients and investigators were masked to treatment allocation until week 156, after which all patients were offered open-label raltegravir until week 240. The primary endpoint was previously assessed at 16 weeks. We assessed long-term efficacy with endpoints of the proportion of patients with an HIV viral load of less than 50 copies per mL and less than 400 copies per mL, and mean change in CD4 cell count, at weeks 156 and 240. FINDINGS: 1012 patients were screened for inclusion. 462 were treated with raltegravir and 237 with placebo. At week 156, 51% in the raltegravir group versus 22% in the placebo group (non-completer classed as failure) had viral loads of less than 50 copies per mL, and 54% versus 23% had viral loads of less than 400 copies per mL. Mean CD4 cell count increase (analysed by an observed failure approach) was 164 cells per μL versus 63 cells per μL. After week 156, 251 patients (54%) from the raltegravir group and 47 (20%) from the placebo group entered the open-label raltergravir phase; 221 (47%) versus 44 (19%) completed the entire study. At week 240, viral load was less than 50 copies per mL in 193 (42%) of all patients initially assigned to raltegravir and less than 400 copies per mL in 210 (45%); mean CD4 cell count increased by 183 cells per μL. Virological failure occurred in 166 raltegravir recipients (36%) during the double-blind phase and in 17 of all patients (6%) during the open-label phase. The most common drug-related adverse events at 5 years in both groups were nausea, headache, and diarrhoea, and occurred in similar proportions in each group. Laboratory test results were similar in both treatment groups and showed little change after year 2. INTERPRETATION: Raltegravir has a favourable long-term efficacy and safety profile in integrase-inhibitor-naive patients with triple-class resistant HIV in whom antiretroviral therapy is failing. Raltegravir is an alternative for treatment-experienced patients, particularly those with few treatment options

Safety, Tolerability, and Efficacy of Raltegravir in a Diverse Cohort of HIV-Infected Patients: 48-Week Results from the REALMRK Study

The racial diversity and gender distribution of HIV-infected patients make it essential to confirm the safety and efficacy of raltegravir in these populations. A multicenter, open-label, single-arm observational study was conducted in a diverse cohort of HIV-infected patients (goals: ≥25% women; ≥50% blacks in the United States), enrolling treatment-experienced patients failing or intolerant to current antiretroviral therapy (ART) and treatment-naive patients (limited to ≤20%). All patients received raltegravir 400 mg b.i.d. in a combination antiretroviral regimen for up to 48 weeks. A total of 206 patients received study treatment at 34 sites in the United States, Brazil, Dominican Republic, Jamaica, and South Africa: 97 (47%) were female and 153 (74%) were black [116 (56%) in the United States]. Of these, 185 patients were treatment experienced: 97 (47%) were failing and 88 (43%) were intolerant to current therapy; 21 patients (10%) were treatment naive. Among treatment-intolerant patients, 55 (63%) had HIV-1 RNA<50 copies/ml at baseline. Overall, 15% of patients discontinued: 13% of men, 18% of women, 14% of blacks, and 17% of nonblacks. At week 48, HIV RNA was <50 copies/ml in 60/94 (64%) patients failing prior therapy, 61/80 (76%) patients intolerant to prior therapy, and 16/21 (76%) treatment-naive patients. Response rates were similar for men vs. women and black vs. nonblack patients. Drug-related clinical adverse events were reported by 8% of men, 18% of women, 14% of blacks, and 9% of nonblacks. After 48 weeks of treatment in a diverse cohort of HIV-infected patients, raltegravir was generally safe and well tolerated with potent efficacy regardless of gender or race

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for a CP-odd Higgs boson decaying to Zh in pp collisions at √s=8TeV with the ATLAS detector

A search for a heavy, CP-odd Higgs boson, A, decaying into a Zboson and a 125GeV Higgs boson, h, with the ATLAS detector at the LHC is presented. The search uses proton–proton collision data at a centre-of-mass energy of 8TeV corresponding to an integrated luminosity of 20.3fb−1. Decays of CP-even hbosons to ττor bbpairs with the Zboson decaying to electron or muon pairs are considered, as well as h →bbdecays with the Zboson decaying to neutrinos. No evidence for the production of an Aboson in these channels is found and the 95% confidence level upper limits derived for σ(gg→A) ×BR(A →Zh) ×BR(h →f¯f)are 0.098–0.013pb for f=τand 0.57–0.014pb for f=bin a range of mA=220–1000GeV. The results are combined and interpreted in the context of two-Higgs-doublet models. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons

Observation of top-quark pair production in association with a photon and measurement of the ttγ production cross section in pp collisions at √s = 7 TeV using the ATLAS detector

A search is performed for top-quark pairs (tt) produced together with a photon (γ) with transverse energy greater than 20 GeV using a sample of tt candidate events in final states with jets, missing transverse momentum, and one isolated electron or muon. The data set used corresponds to an integrated luminosity of 4.59 fb −1 of proton-proton collisions at a center-of-mass energy of 7 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. In total, 140 and 222 ttγ candidate events are observed in the electron and muon channels, to be compared to the expectation of 79 +/- 26 and 120 +/- 39 non-ttγ background events, respectively. The production of ttγ events is observed with a significance of 5.3 standard deviations away from the null hypothesis. The ttγ production cross section times the branching ratio (BR) of the single-lepton decay channel is measured in a fiducial kinematic region within the ATLAS acceptance. The measured value is σ (fid/tty) × BR = 63 +/- 8(stat) (+17/-13)(syst) +/- 1 lumi fb per lepton flavor, in good agreement with the leading-order theoretical calculation normalized to the next-to-leading-order theoretical prediction of 48 +/- 10 fb