140 Impact of TAVI with the Edwards-SAPIEN endoprosthesis on mitral regurgitation: results of a serial echocardiography assessment

PurposeThe impact of transcatheter aortic valve implantation (TAVI) on mitral regurgitation (MR) is controversial. Two recent publications have reported improvement in MR grades following implantation of the Edwards-SAPIEN endoprosthesis. These findings were not replicated with the Core-Valve. The time course of improvement in MR grades with the Edwards-SAPIEN valve has not been described on an individual patient basis and the potential mechanisms of benefit are unclear. The aim of this study was to assess the acute and intermediate changes in MR severity after TAVI with the Edwards-SAPIEN endoprosthesis.MethodsEchocardiography was performed in 22 consecutive patients before and after treatment, and at 1 month follow-up. MR was assessed by color flow mapping and was graded as none, mild, moderate, or severe. MR was defined as organic or functional.ResultsThe aortic valve area increased from pretreatment 0.72cm2 to post-treatment 1.87cm2 and postdischarge 1.81cm2 (P<0.0001). Before intervention MR was present in 73% of the patients. It was mild, moderate, or severe in 36% (n=8), 32% (n=7), and 4% (n=1) respectively. MR was defined as organic in 6 patients (27%) and functional in 10 patients (45%). Compared to baseline, MR grades improved by 1 month (p for trend=0.01). This benefit was secondary to a reduction in regurgitation grades in 50% of patients with an MR at baseline (n=6), while no worsening was observed in the other patients with an MR (n=6) and no occurrence of MR was observed in patients without MR (n=6). A trend for a greater improvement in MR grade was observed in patients with functional MR (n=7, − 1.00) compared to those with an organic MR (n=5, − 0.294; p=0.10).ConclusionIn consecutive patients with a successful implantation of an Edwards-SAPIEN valve a significant improvement in MR was observed. This benefit was secondary to an improvement in 50% of patients with an MR and no worsening in the others

Aldosterone, atherosclerosis and vascular events in patients with stable coronary artery disease

AbstractBackground and aimsPlasma aldosterone has been associated with all-cause and cardiovascular mortality in high-risk cardiovascular populations, including patients with heart failure, myocardial infarction and high-risk coronary artery disease (CAD) patients. In the present study, we evaluated the association of plasma aldosterone levels with vascular events in a large prospective cohort of stable CAD patients recruited in an outpatient setting. Moreover, we investigated the relationship between aldosterone and atherosclerotic burden.Methods and resultsBaseline plasma aldosterone levels were measured in 2699 subjects with CAD (mean age 60±10years, 82% male). During a median follow-up of 4.7years, 308 (11%) patients died, of which 203 were from a vascular cause. Vascular endpoints of myocardial infarction, ischemic stroke or vascular death occurred in 355 (13%) patients. Multivariable Cox regression analysis was performed, adjusting for multiple confounders. Aldosterone (median 96pg/mL, interquartile range 70–138pg/mL, normal range 58–362pg/mL) was independently associated with major vascular events (hazard ratio (HR) 1.56, 95% confidence interval (CI) 1.13–2.15) and vascular mortality (HR 1.95, 95% CI 1.27–3.00). By multivariable regression analysis, aldosterone was also associated with the presence of atherosclerosis in additional vascular territories (cerebrovascular disease and/or peripheral artery disease) (p=0.026).ConclusionsIn patients with stable coronary artery disease, plasma aldosterone is independently associated with the risk of major vascular events and vascular mortality and with atherosclerotic burden

COMPUCEA 2nd generation performance evaluation

COMPUCEA (Combined Procedure for Uranium Concentration and Enrichment Assay) is used for on-site analytical measurements in support of joint Euratom-IAEA inspections during physical inventory verification (PIV) campaigns in European Low-Enriched Uranium (LEU) fuel fabrication plants. The analyses provided on site during the PIV involve the accurate determination of the uranium element content and of the U-235 enrichment in verification samples (uranium product samples of solid form , i.e. powders, pellets) selected by the Safeguards inspectors. These samples are dissolved and then measured by energy-dispersive X-ray absorption edge spectrometry (L-edge densitometry) to obtain the uranium elemental content and gamma spectrometry with a Lanthanum-bromide detector for the U-235 abundance determination. The second generation of COMPUCEA equipment is compact, rugged and ready-to use directly after transport, no cooling of the detectors with liquid nitrogen is required. A software package for comfortable instrument control and data handling has been implemented. The paper describes the technique, setup and calibration procedure of the instrument. Results from PIV campaigns and comparisons between COMPUCEA results with data obtained by remote analysis with a qualified primary analytical method are presented, which demonstrate the performance of the technique. The achieved uncertainties are well within the international target values. First results obtained with a sandwich detector configuration for enhanced detection efficiency of the passive gamma spectrometry and a small separate X-ray fluorescence unit for the pre-screening of the samples for their Gd content are discussed.JRC.E.7-Nuclear Safeguards and Forensic

Prehospital Stroke Triage:A Modeling Study on the Impact of Triage Tools in Different Regions

Background and purpose: Direct transportation to a thrombectomy-capable intervention center is beneficial for patients with ischemic stroke due to large vessel occlusion (LVO), but can delay intravenous thrombolytics (IVT). The aim of this modeling study was to estimate the effect of prehospital triage strategies on treatment delays and overtriage in different regions. Methods: We used data from two prospective cohort studies in the Netherlands: the Leiden Prehospital Stroke Study and the PRESTO study. We included stroke code patients within 6 h from symptom onset. We modeled outcomes of Rapid Arterial oCclusion Evaluation (RACE) scale triage and triage with a personalized decision tool, using drip-and-ship as reference. Main outcomes were overtriage (stroke code patients incorrectly triaged to an intervention center), reduced delay to endovascular thrombectomy (EVT), and delay to IVT. Results: We included 1798 stroke code patients from four ambulance regions. Per region, overtriage ranged from 1-13% (RACE triage) and 3-15% (personalized tool). Reduction of delay to EVT varied by region between 24 ± 5 min (n = 6) to 78 ± 3 (n = 2), while IVT delay increased with 5 (n = 5) to 15 min (n = 21) for non-LVO patients. The personalized tool reduced delay to EVT for more patients (25 ± 4 min [n = 8] to 49 ± 13 [n = 5]), while delaying IVT with 3-14 min (8-24 patients). In region C, most EVT patients were treated faster (reduction of delay to EVT 31 ± 6 min (n = 35), with RACE triage and the personalized tool. Conclusions: In this modeling study, we showed that prehospital triage reduced time to EVT without disproportionate IVT delay, compared to a drip-and-ship strategy. The effect of triage strategies and the associated overtriage varied between regions. Implementation of prehospital triage should therefore be considered on a regional level.</p

The Euratom Safeguards On-site Laboratories at the Reprocessing Plants of La Hague and Sellafield

In the European Union, nuclear material is reprocessed from irradiated power reactor fuel at two sites ¿ La Hague in France and Sellafield in the United Kingdom. These are the largest nuclear sites within the EU, processing many hundreds of tons of nuclear material in a year. Under the Euratom Treaty, the European Commission has the duty to assure that the nuclear material is only used for declared purposes. The Directorate General for Energy (DG ENER), acting for the Commission, assures itself that the terms of Article 77 of Chapter VII of the Treaty have been complied with. In contrast to the Non Proliferation Treaty, the Euratom Treaty requires to safeguard all civil nuclear material in all EU member states ¿ including the nuclear weapons states. The considerable amount of fissile material separated per year (several tonnes) calls for a stringent system of safeguards measures. The aim of safeguards is to deter diversion of nuclear material from peaceful use by maximizing the chance of early detection. At a broader level, it provides assurance to the public that the European nuclear industry, the EU member states and the European Union honour their legal duties under the Euratom Treaty and their commitments to the Non-Proliferation Treaty. Efficient and effective safeguards measures are essential for the public acceptance of nuclear activities.JRC.E.7-Nuclear Safeguards and Forensic

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

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

Numerical Modelling of Corrections relevant to Nuclear Accountancy Measurements by Hybrid K-edge / XRF Densitometry

Hybrid K-edge densitometry (HKED) is a radiometric technique for the non-destructive assay of U and Pu in different types of Nuclear Safeguards samples such as those encountered in existing spent-fuel Reprocessing Plants. A similar Hybrid K-Edge instrument is ready to be installed at an ITU hot cell for measurements on samples from pyro-chemical, as opposed to traditional, reprocessing of spent fuel. Unlike the low-Z matrices of traditional reprocessing samples, the matrices of pyro-reprocessing samples contain high-Z elements, such as Cd or Bi. To reduce the calibration effort normally needed for accurate routine HKED measurements, and to predict the behaviour of unusual samples, e.g. U-Pu mixtures with unusual element ratios or those with high-Z matrices, a Monte Carlo modelling approach was chosen. As the excitation of U and Pu use different fractions of the incident x-ray spectrum, special attention was given to reconstruct accurately the spectrum of the incident x-ray source used as the excitation source in the HKED instrument. In routine measurement of the U/Pu ratio, samples with similar but slightly different composition or density are analysed. A study of the effect of a sample's composition/density variations on experimentally observed U/Pu fluorescence peak area ratios has been undertaken and evaluated.JRC.E.7-Nuclear Safeguards and Forensic

Re-evaluation of spectroscopic characteristics for the 159 keV gamma-line in 242 Pu alpha-decay

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Experimental re-evaluation of the gammy-ray energy and emission probability for the 159 keV transition in 238U followed by the alpha-decay of 242Pu

Because of the very low specific activity of 242Pu, the non-destructive assay of this isotope by means of conventional high-resolution gamma-spectrometry (HRGS) is only possible for Pu samples highly enriched in 242Pu. For bulk samples suffering from the gamma self-attenuation and self-fluorescence effects, the weak gammy-line emitted in the 159 keV transition of 238U practically represents the only choice for the quantitative analysis of 242Pu. A recent study revealed a significant disagreement between the 242Pu mass values in a 99.72 % enriched 242PuO2 sample as reported by HRGS and neutron coincidence counting. This fact motivated the present study on the experimental re-evaluation of the gammy-emission probability for the 159 keV transition using a combination of alpha-, gamma- and mass-spectrometry techniques. The obtained new emission probability P2 = (2.20 ¿ 0.08)¿10-6 turned out to be ¿ 35% smaller than the currently adopted value. The study also suggested a new value E2 = 159.018 ¿ 0.016 keV for the energy of the respective gamma-ray. Keywords: U-238, ground state rotational band, gamma-transition, gamma-ray, emission probability, energy, Pu-242, alpha-decayJRC.DG.E.8-Nuclear Safeguards and Forensic