BackgroundCardiac output (CO) monitoring is a valuable tool for the diagnosis and management of critically ill patients. In the critical care setting, few studies have evaluated the level of agreement between CO estimated by transthoracic echocardiography (CO-TTE) and that measured by the reference method, pulmonary artery catheter (CO-PAC). The objective of the present study was to evaluate the precision and accuracy of CO-TTE relative to CO-PAC and the ability of transthoracic echocardiography to track variations in CO, in critically ill mechanically ventilated patients.MethodsThirty-eight mechanically ventilated patients fitted with a PAC were included in a prospective observational study performed in a 16-bed university hospital ICU. CO-PAC was measured via intermittent thermodilution. Simultaneously, a second investigator used standard-view TTE to estimate CO-TTE as the product of stroke volume and the heart rate obtained during the measurement of the subaortic velocity time integral.ResultsSixty-four pairs of CO-PAC and CO-TTE measurements were compared. The two measurements were significantly correlated (r = 0.95; p < 0.0001). The median bias was 0.2 L/min, the limits of agreement (LOAs) were –1.3 and 1.8 L/min, and the percentage error was 25%. The precision was 8% for CO-PAC and 9% for CO-TTE. Twenty-six pairs of ΔCO measurements were compared. There was a significant correlation between ΔCO-PAC and ΔCO-TTE (r = 0.92; p < 0.0001). The median bias was –0.1 L/min and the LOAs were –1.3 and +1.2 L/min. With a 15% exclusion zone, the four-quadrant plot had a concordance rate of 94%. With a 0.5 L/min exclusion zone, the polar plot had a mean polar angle of 1.0° and a percentage error LOAs of –26.8 to 28.8°. The concordance rate was 100% between 30 and –30°. When using CO-TTE to detect an increase in ΔCO-PAC of more than 10%, the area under the receiving operating characteristic curve (95% CI) was 0.82 (0.62–0.94) (p < 0.001). A ΔCO-TTE of more than 8% yielded a sensitivity of 88% and specificity of 66% for detecting a ΔCO-PAC of more than 10%.ConclusionIn critically ill mechanically ventilated patients, CO-TTE is an accurate and precise method for estimating CO. Furthermore, CO-TTE can accurately track variations in CO.
Immunoreceptors can transduce either inhibitory or activatory signals depending on ligand avidity and phosphorylation status, which is modulated by the protein kinases Lyn and Fyn. Here we show that Lyn and Fyn control immune receptor signaling status. SHP-1 tyrosine 536 phosphorylation by Lyn activates the phosphatase promoting inhibitory signaling through the immunoreceptor. By contrast, Fyn-dependent phosphorylation of SHP-1 serine 591 inactivates the phosphatase, enabling activatory immunoreceptor signaling. These SHP-1 signatures are relevant in vivo, as Lyn deficiency exacerbates nephritis and arthritis in mice, whereas Fyn deficiency is protective. Similarly, Fyn-activating signature is detected in patients with lupus nephritis, underlining the importance of this Lyn–Fyn balance. These data show how receptors discriminate negative from positive signals that respectively result in homeostatic or inflammatory conditions.
Background Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy.Methods This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed.
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