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

Performance improvement of a plasmonic sensor using a combination of AC electrokinetic effects

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Dielectrophoretic capture of low abundance cell population using thick electrodes

International audienceEnrichment of rare cell populations such as Circulating Tumor Cells (CTCs) is a critical step before performing analysis. This paper presents a polymeric microfluidic device with integrated thick Carbon-PolyDimethylSiloxane composite (C-PDMS) electrodes designed to carry out dielectrophoretic (DEP) trapping of low abundance biological cells. Such conductive composite material presents advantages over metallic structures. Indeed, as it combines properties of both the matrix and doping particles, C-PDMS allows the easy and fast integration of conductive microstructures using a soft-lithography approach while preserving O2 plasma bonding properties of PDMS substrate and avoiding a cumbersome alignment procedure. Here, we first performed numerical simulations to demonstrate the advantage of such thick C-PDMS electrodes over a coplanar electrode configuration. It is well established that dielectrophoretic force (FDEP) decreases quickly as the distance from the electrode surface increases resulting in coplanar configuration to a low trapping efficiency at high flow rate. Here, we showed quantitatively that by using electrodes as thick as a microchannel height, it is possible to extend the DEP force influence in the whole volume of the channel compared to coplanar electrode configuration and maintaining high trapping efficiency while increasing the throughput. This model was then used to numerically optimize a thick C-PDMS electrode configuration in terms of trapping efficiency. Then, optimized microfluidic configurations were fabricated and tested at various flow rates for the trapping of MDA-MB-231 breast cancer cell line. We reached trapping efficiencies of 97% at 20 μl/h and 78.7% at 80 μl/h, for 100 μm thick electrodes. Finally, we applied our device to the separation and localized trapping of CTCs (MDA-MB-231) from a red blood cells sample (concentration ratio of 1:10)

Clinical spectrum and short-term outcome of adult patients with purpura fulminans: a French multicenter retrospective cohort study

International audiencePurpose - Data on purpura fulminans (PF) in adult patients are scarce and mainly limited to meningococcal infections. Our aim has been to report the clinical features and outcomes of adult patients admitted in the intensive care unit (ICU) for an infectious PF, as well as the predictive factors for limb amputation and mortality. Methods - A 17-year national multicenter retrospective cohort study in 55 ICUs in France from 2000 to 2016, including adult patients admitted for an infectious PF defined by a sudden and extensive purpura, together with the need for vasopressor support. Primary outcome variables included hospital mortality and amputation during the follow-up period (time between ICU admission and amputation, death or end of follow-up). Results - Among the 306 included patients, 126 (41.2%; 95% CI 35.6-46.9) died and 180 (58.8%; 95% CI 53.3-64.3) survived during the follow-up period [13 (3-24) days], including 51/180 patients (28.3%, 95% CI 21.9-35.5) who eventually required limb amputations, with a median number of 3 (1-4) limbs amputated. The two predominantly identified microorganisms were Neisseria meningitidis (63.7%) and Streptococcus pneumoniae (21.9%). By multivariable Cox model, SAPS II [hazard-ratio (HR) = 1.03 (1.02-1.04); p < 0.001], lower leucocytes [HR 0.83 (0.69-0.99); p = 0.034] and platelet counts [HR 0.77 (0.60-0.91); p = 0.007], and arterial blood lactate levels [HR 2.71 (1.68-4.38); p < 0.001] were independently associated with hospital death, while a neck stiffness [HR 0.51 (0.28-0.92); p = 0.026] was a protective factor. Infection with Streptococcus pneumoniae [sub-hazard ratio 1.89 (1.06-3.38); p = 0.032], together with arterial lactate levels and ICU admission temperature, was independently associated with amputation by a competing risks analysis. Conclusion - Purpura fulminans carries a high mortality and morbidity. Pneumococcal PF leads to a higher risk of amputation. Trials registration - NCT03216577

The association of cardiovascular failure with treatment for ventilator-associated lower respiratory tract infection

Purpose: Ventilator associated-lower respiratory tract infections (VA-LRTIs), either ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), accounts for most nosocomial infections in intensive care units (ICU) including. Our aim was to determine if appropriate antibiotic treatment in patients with VA-LRTI will effectively reduce mortality in patients who had cardiovascular failure. Methods: This was a pre-planned subanalysis of a large prospective cohort of mechanically ventilated patients for at least 48 h in eight countries in two continents. Patients with a modified Sequential Organ Failure Assessment (mSOFA) cardiovascular score of 4 (at the time of VA-LRTI diagnosis and needed be present for at least 12 h) were defined as having cardiovascular failure. Results: VA-LRTI occurred in 689 (23.2%) out of 2960 patients and 174 (25.3%) developed cardiovascular failure. Patients with cardiovascular failure had significantly higher ICU mortality than those without (58% vs. 26.8%; p < 0.001; OR 3.7; 95% CI 2.6–5.4). A propensity score analysis found that the presence of inappropriate antibiotic treatment was an independent risk factor for ICU mortality in patients without cardiovascular failure, but not in those with cardiovascular failure. When the propensity score analysis was conducted in patients with VA-LRTI, the use of appropriate antibiotic treatment conferred a survival benefit for patients without cardiovascular failure who had only VAP. Conclusions: Patients with VA-LRTI and cardiovascular failure did not show an association to a higher ICU survival with appropriate antibiotic treatment. Additionally, we found that in patients without cardiovascular failure, appropriate antibiotic treatment conferred a survival benefit for patients only with VAP. Trial registry: ClinicalTrials.gov, number NCT01791530. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature