Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

RF inductive probe to measure plasma complex conductivity

Invited talk, publication in 2017: Electromagnetic, complex image model of a large area RF resonant antenna as inductive plasma source Ph Guittienne, R Jacquier, A A Howling, and I Furno. Plasma Sources, Sci. Technol. 26, 035010 (2017)

Ion heating and flows in a high power helicon source

We report experimental measurements of ion temperatures and flows in a high power, linear, magnetized, helicon plasma device, the Resonant Antenna Ion Device (RAID). Parallel and perpendicular ion temperatures on the order of 0.6 eV are observed for an rf power of 4 kW, suggesting that higher power helicon sources should attain ion temperatures in excess of 1 eV. The unique RAID antenna design produces broad, uniform plasma density and perpendicular ion temperature radial profiles. Measurements of the azimuthal flow indicate rigid body rotation of the plasma column of a few kHz. When configured with an expanding magnetic field, modest parallel ion flows are observed in the expansion region. The ion flows and temperatures are derived from laser induced fluorescence measurements of the Doppler resolved velocity distribution functions of argon ions. Published by AIP Publishing

Helicon wave-generated plasmas for negative ion beams for fusion

In the next generation of fusion reactors, such as DEMO, neutral beam injectors (NBIs) of high energy (0.8-1 MeV) deuterium atoms with high wall-plug efficiency (>50%) will be required to reach burning plasma conditions and to provide a significant amount of current drive. The present NBI system for DEMO assumes that 50 MW is delivered to the plasma by 3 NBIs. In the Siphore NBI concept, negative deuterium ions are extracted from a long, thin ion source 3 m high and 15 cm wide, accelerated and subsequently photo-neutralized. This requires the development of a new generation of negative ion sources. At the Swiss Plasma Center, a novel radio frequency helicon plasma source, based on a resonant network antenna source delivering up to 10 kW at 13.56 MHz, has been developed and is presently under study on the Resonant Antenna Ion Device (RAID). RAID is a linear device (1.9 m total length, 0.4 m diameter) and is equipped with an extensive set of diagnostics for full plasma characterization. In this work, the principles of operation of resonant antennas as helicon sources are introduced. We present absolute spectroscopy, Langmuir probe, and interferometry measurements on helicon plasmas. We characterize the performance of the source in terms of hydrogen/deuterium dissociation and negative ion production as a function of the input power. Furthermore, first results with the helicon birdcage antenna installed on the Cybele negative ion source at CEA-IRFM are presented, as a first step towards the validation of the Siphore concept

Inhibition of proprotein convertases enhances cell migration and metastases development of human colon carcinoma cells in a rat model

Although proprotein convertases are involved in tumor development, nothing is known about their role in metastatic dissemination. To investigate the involvement of convertase inhibition, we used human colon carcinoma cells overexpressing α1-antitrypsin Portland (α1-PDX, PDX39P cells), a potent convertase inhibitor. We previously reported that these cells bear uncleaved integrin α subunits and display an altered attachment to vitronectin that is correlated with defects in the intracellular signaling pathways activated by αvβ5 integrin ligation. In this study, we demonstrate that the inhibition of proprotein convertase activity either by overexpression of α1-PDX or with the synthetic inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethylketone (dec-RVKR-cmk) led to a significant increase in cell migration supported by the αvβ5 integrin. A collagen gel invasion assay showed that PDX39P cells also displayed an invasive ability, contrary to control cells. Moreover, when injected to immunosuppressed newborn rats, PDX39P cells were highly invasive, as they induce 10 times more metastases than mock-transfected cells. In addition, the aggressiveness of PDX39P cells can be greatly reduced by a function-blocking monoclonal antibody (mAb) against the αv subunit. It thus seems that inhibition of proprotein convertases enhances the in vivo invasiveness of colon tumor cells likely due to an increase in cell migration mediated by αv integrins

Helicon volume production of H−^− and D−^− using a resonant birdcage antenna on RAID

International audienceNegative ion production by volumetric processes is investigated in the RAID linear device using experiments and modeling. Measurements by optical emission spectroscopy, cavity ring-down spectroscopy, and Langmuir probe assisted laser photodetachment are combined and reveal that H$^−$ and D$^−$ ions are distributed in a halo around the plasma column with densities of 2 × 10$^{16}$ m$^{-3}$ for only a few kilowatts of RF power in a Cs-free plasma. A hydrogen transport fluid code shows that RAID plasmas have a hot electron core favorable to ro-vibrational excitation and dissociation of H$_2$ molecules. Dissociative attachment to ro-vibrationally excited H$_2$ molecules is the only significant source of H$^−$ anywhere in the RAID volum

Efficacy of Chest CT for COVID-19 Pneumonia Diagnosis in France

International audienceThe role and performance of chest CT in the diagnosis of the coronavirus disease 2019 (COVID-19) pandemic remains under active investigation. Purpose To evaluate the French national experience using chest CT for COVID-19, results of chest CT and reverse transcription polymerase chain reaction (RT-PCR) assays were compared together and with the final discharge diagnosis used as the reference standard. Materials and Methods A structured CT scan survey (NCT04339686) was sent to 26 hospital radiology departments in France between March 2, 2020, and April 24, 2020. These dates correspond to the peak of the national COVID-19 epidemic. Radiology departments were selected to reflect the estimated geographic prevalence heterogeneities of the epidemic. All symptomatic patients suspected of having COVID-19 pneumonia who underwent both initial chest CT and at least one RT-PCR test within 48 hours were included. The final discharge diagnosis, based on multiparametric items, was recorded. Data for each center were prospectively collected and gathered each week. Test efficacy was determined by using the Mann-Whitney test, Student t test, χ2 test, and Pearson correlation coefficient. P < .05 indicated a significant difference. Results Twenty-six of 26 hospital radiology departments responded to the survey, with 7500 patients entered; 2652 did not have RT-PCR test results or had unknown or excess delay between the RT-PCR test and CT. After exclusions, 4824 patients (mean age, 64 years ± 19 [standard deviation], 2669 male) were included. With final diagnosis as the reference, 2564 of the 4824 patients had COVID-19 (53%). Sensitivity, specificity, negative predictive value, and positive predictive value of chest CT in the diagnosis of COVID-19 were 2319 of 2564 (90%; 95% CI: 89, 91), 2056 of 2260 (91%; 95% CI: 91, 92), 2056 of 2300 (89%; 95% CI: 87, 90), and 2319 of 2524 (92%; 95% CI: 91, 93), respectively. There was no significant difference for chest CT efficacy among the 26 geographically separate sites, each with varying amounts of disease prevalence. Conclusion Use of chest CT for the initial diagnosis and triage of patients suspected of having coronavirus disease 2019 was successful