Because of increased access to kidney transplantation in elderly subjects, the prevalence of monoclonal gammopathies of unknown significance (MGUS) in kidney transplantation (KT) is growing. However, ...little is known about the consequences of MGUS on long-term outcomes.
We identified 70 recipients with MGUS present at transplantation (KTMG) and 114 patients with MGUS occurring after KT (DNMG), among 3059 patients who underwent a KT in two French kidney transplantation centers. We compared outcomes of KTMG with those of matched controls.
Baseline characteristics were similar except for an older age in KTMG compared with the DNMG group (62 vs 57 years, P = .03). Transient MGUS occurred more frequently in DNMG patients (45% vs 24%, P = .007). When compared with matched controls without MGUS, KTMG patients showed higher frequency and earlier post-transplant solid cancers (15% vs 5%, P = .04) and a trend for more bacterial infections (63% vs 48%, P = .08), without difference regarding patient and graft survival, rejection episodes or hematological complications. KTMG patients with an abnormal kappa/lambda ratio and/or severe hypogammaglobulinemia at the time of KT experienced shorter overall survival.
MGUS detection at the time of KT is neither associated with a higher occurrence of graft rejection, nor adversely affects graft or overall survival. MGUS should not contraindicate KT. However, MGUS at the time of KT may be associated with higher risk of early neoplastic and infectious complications and warrants prolonged surveillance. Measurement of serum free light chain should be performed before transplant to refine the risk evaluation of KTMG patients and propose personalized follow-up and immunosuppression.
Neurological biomarkers are particularly valuable to clinicians as they can be used for diagnosis, prognosis, or response to treatment. This field of neurology has evolved considerably in recent ...years with the improvement of analytical methods, allowing the detection of biomarkers not only in cerebrospinal fluid (CSF) but also in less invasive fluids like blood. These advances greatly facilitate the repeated quantification of biomarkers, including at asymptomatic stages of the disease. Among the various informative biomarkers of neurological disorders, neurofilaments (NfL) have proven to be of particular interest in many contexts, such as neurodegenerative diseases, traumatic brain injury, multiple sclerosis, stroke, and cancer. Here we discuss these different pathologies and the potential value of NfL assay in the management of these patients, both for diagnosis and prognosis. We also describe the added value of NfL compared to other biomarkers currently used to monitor the diseases described in this review.
•Galectin-3 concentrations do not seem affected in MIS-C.•Entry NT-proBNP and BNP are higher in patients with cardiogenic shock than without.•NT-proBNP possibly allows earlier detection of cardiac ...involvement than BNP.
Since the COVID-19 pandemic began, a cohort of Multisystem inflammatory syndrome in children (MIS-C) patients has been described. Cardiac involvement is found in 80–85% patients, typically with cardiac dysfunction with or without cardiogenic shock. Here, three cardiac biomarkers, BNP, NT-proBNP and Galectin-3 were compared for the first time in MIS-C in a unique cohort of hospitalized French children.
Fourteen children with MIS-C hospitalized at Necker-Enfants Malades for cardiac management during the first three COVID-19 waves (March 2020-March 2021) were included. All had positive SARS-CoV-2 serology and proven cardiac involvement assessed by transthoracic echocardiography. NT-proBNP, BNP and Galectin-3 were measured at admission, discharge and first follow-up clinic.
All admission Galectin-3 measurements were comprised within the reference interval, both in patients with and without cardiogenic shock, and did not vary between admission, discharge and first follow-up clinic. Both median admission BNP and NT-proBNP were higher in children with cardiogenic shock than without. Median admission NT-proBNP was higher than its predictive positive value in heart failure in both groups of children, while median BNP was below its negative predictive value in children without cardiogenic shock but with cardiac dysfunction.
Galectin-3 does not seem affected by MIS-C. NT-proBNP seems to increase more precociously than BNP possibly making it a more sensitive marker for screening of heart failure in MIS-C.
Urine neutrophil gelatinase-associated lipocalin (uNGAL) has been shown to accurately predict and allow early detection of AKI, as assessed by an increase in serum creatinine in children and adults. ...The present study explores the accuracy of uNGAL for the prediction of severe AKI-related outcomes in neonates and infants undergoing cardiac surgery: dialysis requirement and/or death within 30 days.
Prospective, observational cohort study conducted in a tertiary referral pediatric cardiac intensive care unit, including 75 neonates and 125 infants undergoing surgery with cardiopulmonary bypass between August 1, 2010, and May 31, 2011. Urine samples were collected before surgery and at median of five time points within 48 hours of bypass. Urine NGAL was quantified as absolute concentration, creatinine-normalized concentration, and absolute excretion rate, and a clusterization algorithm was applied to the individual uNGAL kinetics. The accuracy for the prediction of the outcome was assessed using receiver-operating characteristic areas, likelihood ratios, diagnostic odds ratios, net reclassification index, integrated reclassification improvement, and number needed to screen.
A total of 1176 urine samples were collected. Of all patients, 8% required dialysis and 4% died. Three clusters of uNGAL kinetics were identified, including patients with significantly different outcomes. The uNGAL level peaked between 1 and 3 hours of bypass and remained high in half of all patients who required dialysis or died. The uNGAL levels measured within 24 hours of bypass accurately predicted the outcome and performed best after normalization to creatinine, with varying cutoffs according to the time elapsed since bypass. The number needed to screen to correctly identify the risk of dialysis or death in one patient varied between 1.5 and 2.6 within 12 hours of bypass.
uNGAL is a valuable predictive tool of dialysis requirement and death in neonates and infants with AKI after cardiac surgery.
Disposition of gentamicin and amikacin during extracorporeal membrane oxygenation has not been addressed in in vitro models. The HLS Advanced 7.0® circuit with the Cardio Help® monitor, Getinge, was ...used. The 5-L central compartment (CC) was loaded with gentamicin and amikacin at a targeted concentration of 40 and 80 mg/L in the same bag prior connection to the circuit. Samples were collected in the CC, the inlet and outlet ports from 15 min to 6 h post-connection. Pharmacokinetic analyses were performed using the NeckEpur® method. Analysis of results of gentamicin and amikacin showed in the filter-pump block (i) the extremely low value of the extraction coefficients, (ii) similar values of the areas under the curve (AUCs) at the inlet and outlet ports, (iii) using the Wilcoxon matched pairs signed rank test no significant differences of the inlet-outlet concentrations in the filter-pump. In the whole system (i) the amounts recovered in the CC at the end of the 6-h session were not significantly different from the initial values, (ii) the extremely low values of the total clearance of gentamicin and amikacin from the CC in comparison with the measured simulated blood flowrate, (iii) the lack of significant time-concentration interactions in the CC and the inlet and outlet ports. These findings allow concluding no detectable adsorption of gentamicin and amikacin occurred in the HLS Advanced 7.0 circuit.
Abstract This study investigated the proapoptotic effects of oxidized low density lipoprotein (oxLDL), which plays a key role in atherogenesis, on normal fresh human monocytes isolated from ...peripheral blood (PBMs), on human monocyte-derived macrophages, and on U937 monocytic cell line. OxLDL were generated by hypochlorous acid (HOCl) treatment of native LDL. We demonstrated that HOCl–oxLDL (200 μg/ml) induced apoptosis in PBMs and U937 cells via the mitochondrial pathway, whereas it failed to induce apoptosis in human monocyte-derived macrophages. OxLDL-induced U937 cells apoptosis involved ROS generation, mitochondrial Bax translocation with a disruption of mitochondrial membrane potential, cytosolic liberation of cytochrome c and subsequently activation of caspases-9 and -3. The interference of ROS scavengers N -acetylcysteine and catalase with HOCl–oxLDL-induced apoptosis further supports the importance of mitochondrial ROS production in this process. Bcl-2 overexpression prevented Bax translocation whereas it failed to prevent ROS generation indicating that ROS is an upstream signal for inducing mitochondrial apoptotic damages. Because monocyte apoptosis could limit early atheroma formation, it will be interesting to identify the signaling pathway(s) induced by HOCl–oxLDL leading to ROS generation. In contrast, monocyte-derived macrophages, which resist to HOCl–oxLDL-induced oxidative stress, may promote atherosclerosis.
Objective The present study aimed to assess the usefulness of routine monitoring of cardiac troponin I concentrations within 24 hours of surgery (cTn-I<24h) in neonates and infants undergoing cardiac ...surgery. Methods The added predictive ability of a high peak cTn-I<24h (within the upper quintile per procedure) for a composite outcome, including 30-day mortality and severe morbidity, was assessed retrospectively. The predicted risk for the composite outcome was estimated from a logistic regression model including preoperative and intraoperative variables. Adding a high peak cTn-I<24h to the risk model resulted in reclassification of the predicted risk. It also allowed quantification of the improvement in reclassification and discrimination by the difference between c-indexes, the Net Reclassification and the Integrated Discrimination Indexes (NRI and IDI). Results Overall, 1023 consecutive patients were included. Adding a high peak cTn-I<24h to the model resulted in no improvement in reclassification or discrimination in the overall population (difference between c-indexes: 0.011 −0.004 to 0.029, NRI = 0.06, P = .22, IDI = 0.02, P = .06), except in a subgroup of patients undergoing the arterial switch operation with or without ventricular septal defect closure and/or aortic arc repair, anomalous origin of the left coronary artery from the pulmonary artery repair, truncus arteriosus repair, Norwood procedure, and Sano modification, in whom NRI = 0.23 ( P = .005) and IDI = 0.05 ( P < .001). Conclusions Patients with coronary anomalies and patients with reduced ventricular mass should benefit from the routine monitoring of cTn-I concentrations after surgery for congenital cardiac disease.
Measurement of the haemolysis index (HI) is usually performed in clinical chemistry laboratories in order to inform about whether biological analyses are influenced by in vivo or in vitro haemolysis ...of the specimen. Our aim was to evaluate the analytical performance of Abbott C-16000 analyser HI measurement in order to determine whether this could be used to reliably measure cell-free haemoglobin (fHB) in plasma samples.
The repeatability, reproducibility, lower limit of detection (LLOD) and lower limit of quantification (LLOQ) of C-16000 HI measurement were determined as well as the potential interference of bilirubin, triglycerides and myoglobin. C-16000 HI values of biological samples with various ranges of fHB were compared to those measured using the established reference method, second-derivate spectroscopy.
Results: C-16000 HI determination showed excellent linear correlation with the reference method (y = 1.0043x – 1.248, R² = 0.998), a broad analytical measurement range (400-20,000 mg/L; y = 0.9904x + 72.972, R² = 0.999), clinically relevant LLOD (56 mg/L) and LLOQ (84 mg/L), good repeatability (coefficient of variation (CV) = 1-15%) and good reproducibility (CV = 5-7%). No interference was observed with myoglobin at concentrations as high as 35,447 mg/L, unconjugated and conjugated bilirubin (at concentrations up to 500 mg/L and 375 mg/L, respectively) or triglycerides up to 6.8 mmol/L. However, a significant underestimation of fHB concentrations was observed at higher triglyceride levels.
This study demonstrates that Abbott C-16000 analyser HI is reliable and accurately measures plasma fHB concentrations under pathophysiological conditions except when there are high blood concentrations of triglycerides.
A five-year-old boy is presented to Necker hospital for a dilated hypertrophic cardiomyopathy. The implantation of the Berlin Heart Excor
ventricular assist device was performed. This pediatric-sized ...Berlin Heart
device provides mechanical support for young infants and children of all ages to sustain the failing cardiac circulation over several months, until either recovery of myocardial function or heart transplantation. It remains difficult to identify patients with sufficient recovery and the right time for explantation of the Berlin Heart
. Currently, the decision as to whether a patient should be weaned from the system is mainly based on echocardiographic data. Humoral biomarker, associated to echocardiographic features, would be helpful to identify children who might recover without heart transplantation. We observed that our young patient presented highly elevated BNP plasma levels before mechanical support, and a significant decrease during Berlin Heart
support. Monitoring levels of BNP can be helpful to detect appropriate unloading of the heart as a precondition for recovery. During pump-stop maneuvers, BNP should be regarded in combination with clinical and hemodynamic status of the patients, associated with echocardiographic data.
We compared the apoptotic mechanism involved in U937 human monocytic cell line in presence of oxidized low-density lipoproteins (oxLDL) obtained after treatment with hypochlorous acid (HOCl) or ...copper (Cu).
Both types of oxLDL induced U937 apoptotic cell death via the mitochondrial pathway. In contrast to HOCl-oxLDL, Cu-oxLDL induced apoptosis
via a caspase-independent mechanism, with no activation of pro-caspase-3, but
via the release of apoptosis inducing factor (AIF) from mitochondria.
The apoptotic program of the monocyte differs depending on the mode of LDL oxidation, based on differences in the oxidatively modified components of the two oxLDL types.
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