Intensification of Antiretroviral Therapy with a CCR5 Antagonist in Patients with Chronic HIV-1 Infection: Effect on T Cells Latently Infected

Objective: The primary objective was to assess the effect of MVC intensification on latently infected CD4+ T cells in chronically HIV-1-infected patients receiving antiretroviral therapy. Methods: We performed an open-label pilot phase II clinical trial involving chronically HIV-1-infected patients receiving stable antiretroviral therapy whose regimen was intensified with 48 weeks of maraviroc therapy. We analyzed the latent reservoir, the residual viremia and episomal 2LTR DNA to examine the relationship between these measures and the HIV-1 latent reservoir, immune activation, lymphocyte subsets (including effector and central memory T cells), and markers associated with bacterial translocation. Results: Overall a non significant reduction in the size of the latent reservoir was found (p = 0.068). A mean reduction of 1.82 IUPM was observed in 4 patients with detectable latent reservoir at baseline after 48 weeks of intensification. No effect on plasma residual viremia was observed. Unexpectedly, all the patients had detectable 2LTR DNA circles at week 24, while none of them showed those circles at the end of the study. No changes were detected in CD4+ or CD8+ counts, although a significant decrease was found in the proportion of HLA-DR+/CD38+ CD4+ and CD8+ T-cells. LPS and sCD14 levels increased. Conclusions: Intensification with MVC was associated with a trend to a decrease in the size of the latent HIV-1 reservoir in memory T cells. No impact on residual viremia was detected. Additional studies with larger samples are needed to confirm the results

NOEMA spatially resolved view of the multiphase outflow in IRAS17020+4544: a shocked wind in action?

Funding Information: We are grateful to the anonymous referee for their careful review of the manuscript that significantly improved our publication. This work is based on observations carried out under project number W17CR with the IRAM NOEMA Interferometer. IRAM is supported by INSU/CNRS (France), MPG (Germany), and IGN (Spain). This research has used data obtained from the Chandra Data Archive and the Chandra Source Catalog, and software provided by the Chandra X-ray Center (CXC) in the application package ciao . The author is grateful to the Chandra-CXC Helpdesk and to H. Marshall and D. Huenemoerder for their support on the treatment of the HRC-LETG data. ALL and QS acknowledge support from CONACyT grant CB-2016-01-286316. ALL acknowledges support from DGAPA-PAPIIT grant IA101623. YK acknowledges support from DGAPA-PAPIIT grant IN106518 and 102023. VMPA and VC acknowledge support from CONACyT research grants 280789 and 320987. C.F. acknowledges support from the PRIN MIUR project “Black hole winds and the baryon life cycle of galaxies: the stone-guest at the galaxy evolution supper”, contract 2017PH3WAT.This work is supported by the MPIfR-Mexico Max Planck Partner Group led by V.M.P.-A. SGB acknowledges support from the research project PID2019-106027GA-C44 of the Spanish Ministerio de Ciencia e Innovación. ALL acknowledges the staff of the European Space Astronomy Centre (ESAC, Madrid) for hosting her visit during which this work was partly finalized. Financial support is acknowledged from ESA through the Science Faculty – Funding reference ESA-SCI-SC-LE-123, and from project PID2019-107408GB-C41 by the Spanish Ministry of Science and Innovation/State Agency of Research MCIN/AEI/ 10.13039/501100011033. Funding Information: We are grateful to the anonymous referee for their careful review of the manuscript that significantly improved our publication. This work is based on observations carried out under project number W17CR with the IRAM NOEMA Interferometer. IRAM is supported by INSU/CNRS (France), MPG (Germany), and IGN (Spain). This research has used data obtained from the Chandra Data Archive and the Chandra Source Catalog, and software provided by the Chandra X-ray Center (CXC) in the application package CIAO. The author is grateful to the Chandra-CXC Helpdesk and to H. Marshall and D. Huenemoerder for their support on the treatment of the HRC-LETG data. ALL and QS acknowledge support from CONACyT grant CB-2016-01-286316. ALL acknowledges support from DGAPAPAPIIT grant IA101623. YK acknowledges support from DGAPAPAPIIT grant IN106518 and 102023. VMPA and VC acknowledge support from CONACyT research grants 280789 and 320987. C.F. acknowledges support from the PRIN MIUR project “Black hole winds and the baryon life cycle of galaxies: the stone-guest at the galaxy evolution supper”, contract 2017PH3WAT.This work is supported by the MPIfR-Mexico Max Planck Partner Group led by V.M.P.-A. SGB acknowledges support from the research project PID2019-106027GA-C44 of the Spanish Ministerio de Ciencia e Innovación.ALL acknowledges the staff of the European Space Astronomy Centre (ESAC, Madrid) for hosting her visit during which this work was partly finalized. Financial support is acknowledged from ESA through the Science Faculty – Funding reference ESA-SCI-SC-LE-123, and from project PID2019-107408GB-C41 by the Spanish Ministry of Science and Innovation/State Agency of Research MCIN/AEI/10.13039/501100011033. Publisher Copyright: © 2023 The Author(s).The Narrow Line Seyfert 1 Galaxy IRAS17020+4544 is one of the few active galactic nuclei (AGNs) where a galaxy-scale energy-conserving outflow was revealed. This paper reports on NOEMA observations addressed to constrain the spatial scale of the CO emission in outflow. The molecular outflowing gas is resolved in five components tracing approaching and receding gas, all located at a distance of 2–3 kpc on the west and east sides of the active nucleus. This high-velocity gas (up to vout = ±1900 km s-1) is not coincident with the rotation pattern of the CO gas in the host galaxy disc. The estimated mass outflow rate shows that with a global mass output of M·H2 = 139±20 M☉ yr-1, this powerful galaxy-scale outflow is consistent with the wind conserving its energy, and with a momentum rate boost of a factor of ∼30 compared to the momentum rate of the nuclear X-ray wind. Preliminary results from ancillary X-ray (Chandra) and radio images (e-MERLIN) are reported. While the nature of the radio source is not conclusive, the Chandra image may tentatively trace extended emission, as expected by an expanding bubble of hot X-ray gas. The outcome of the NOEMA analysis and of the past and ongoing publications dedicated to the description of the outflow multiband phenomenology in IRAS17020+4544 concur to provide compelling reasons to postulate that an outflow shocking with the galaxy interstellar medium is driving the multiphase wind in this peculiar AGN.Peer reviewe

International Nosocomial Infection Control Consortiu (INICC) report, data summary of 43 countries for 2007-2012. Device-associated module

We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2007-December 2012 in 503 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study using the Centers for Disease Control and Prevention's (CDC) U.S. National Healthcare Safety Network (NHSN) definitions for device-associated health care–associated infection (DA-HAI), we collected prospective data from 605,310 patients hospitalized in the INICC's ICUs for an aggregate of 3,338,396 days. Although device utilization in the INICC's ICUs was similar to that reported from ICUs in the U.S. in the CDC's NHSN, rates of device-associated nosocomial infection were higher in the ICUs of the INICC hospitals: the pooled rate of central line–associated bloodstream infection in the INICC's ICUs, 4.9 per 1,000 central line days, is nearly 5-fold higher than the 0.9 per 1,000 central line days reported from comparable U.S. ICUs. The overall rate of ventilator-associated pneumonia was also higher (16.8 vs 1.1 per 1,000 ventilator days) as was the rate of catheter-associated urinary tract infection (5.5 vs 1.3 per 1,000 catheter days). Frequencies of resistance of Pseudomonas isolates to amikacin (42.8% vs 10%) and imipenem (42.4% vs 26.1%) and Klebsiella pneumoniae isolates to ceftazidime (71.2% vs 28.8%) and imipenem (19.6% vs 12.8%) were also higher in the INICC's ICUs compared with the ICUs of the CDC's NHSN

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. RESULTS: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. CONCLUSION: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk