Dimitri Titeca‐Beauport

BACKGROUND: Cardiac 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. METHODS: Thirty-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. RESULTS: Sixty-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%. CONCLUSION: In 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.Src-family kinases Fyn and Lyn are signaling components downstream of ITAM-bearing antigen receptors. Here the authors show that by phosphorylating SHP-1 at different residues, Lyn and Fyn can have opposing regulatory effects on ITAM receptors.

IntroductionAlthough kidney transplantation carries a survival benefit compared with dialysis, mortality, especially the first year after transplantation, is high in recipients older than 70. The aim of this study was to evaluate early death and graft failure, and to determine the risk factors associated with these events in this specific population.MethodsAll patients older than 70 years who received a kidney transplant between January 2000 and December 2014 in the North-West of France were included (n = 171). Baseline characteristics and outcomes after transplantation were studied. Kaplan-Meier analysis was performed to assess patient and graft survival, and Cox regression analysis to evaluate risk factors for graft failure and patient death.ResultsThe mean recipient age was 73.3 ± 2.5 years. Death-censored graft survival at 1, 3, and 5 years were 82.6%, 78.7%, and 75.4%, respectively. Patient survival at 1, 3, and 5 years was 90.1%, 82.5%, and 68.1%, respectively. One year after transplantation, 17 patients (9.9%) were dead, mainly from infectious (58.5%) or cardiovascular disease (29.4%). According to the Cox multivariate analysis, the independent risk factors for death or graft failure during the first year were arrhythmia (odds ratio [OR] 2.26; 95% confidence interval [CI] 1.08–4.8), left-ventricular ejection fraction (LVEF) under 56% (OR 2.38; 95% CI 1.18–4.83), human leucocyte antigen (HLA) antibodies (OR 2.1; 95% CI 1.04–4.2), deceased donor from cardiovascular cause (OR 5.18; 95% CI 1.22–6.3), and acute rejection (OR 2.77; 95% CI 1.2–6.3).ConclusionIn kidney transplant recipients older than 70 years, cardiac evaluation and immunosuppression optimization seem to be crucial to improve short-term patient and graft survival.

BACKGROUND: The risk of early death is particularly high in patients over the age of 65 presenting with antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis. We hypothesized that by combining disease severity markers, a comorbidity index and serious adverse event reports, we would be able to identify early predictors of one-year mortality in this population. METHODS: We performed a multicentre, retrospective study in the nephrology and internal medicine departments of six tertiary hospitals in northern France. A total of 149 patients (median [interquartile range (IQR)] age: 72.7 [68.5-76.8] years) presenting with ANCA-associated vasculitis and renal involvement were included between January 2002 and June 2015. The primary endpoint was the one-year mortality rate. RESULTS: Renal function was severely impaired at presentation (median [IQR] peak serum creatinine (SCr): 337 [211-522] μmol/l), and 45 patients required dialysis. The Five-Factor Score (FFS, scored as + 1 point for each poor prognostic factor (age > 65 years, cardiac symptoms, gastrointestinal involvement, SCr ≥150 μmol/L, and the absence of ear, nose, and throat involvement)) was ≥3 in 120 cases. The one-year mortality rate was 19.5%. Most of the deaths occurred before month 6, and most of these were related to severe infections. In a univariate analysis, age, a high comorbidity index, a performance status of 3 or 4, a lack of co-trimoxazole prophylaxis, early severe infection, and disease activity parameters (such as the albumin level, haemoglobin level, peak SCr level, dialysis status, and high FFS) were significantly associated with one-year mortality. In a multivariable analysis, the best predictors were a high FFS (relative risk (RR) [95% confidence interval (CI)] = 2.57 [1.30-5.09]; p = 0.006) and the occurrence of a severe infection during the first month (RR [95%CI] = 2.74 [1.27-5.92]; p = 0.01). CONCLUSIONS: When considering various disease severity markers in over-65 patients with ANCA-associated renal vasculitis, we found that an early, severe infection (which occurred in about a quarter of the patients) is a strong predictor of one-year mortality. A reduction in immunosuppression, the early detection of infections, and co-trimoxazole prophylaxis might help to reduce mortality in this population.