Early recognition of cardiac surgery-associated acute kidney injury: lack of added value of TIMP2 IGFBP7 over short-term changes in creatinine (an observational pilot study).

BACKGROUND: For the detection of cardiac surgery-associated acute kidney injury (CS-AKI), the performance of urine tissue inhibitor of metalloproteinase 2 insulin-like growth factor-binding protein 7 (TIMP2 IGFBP7) has never been compared with that of very early changes in plasma creatinine (∆pCr). We hypothesized that, in the context of perioperative haemodilution, lack of postoperative decrease in pCr would be of honourable performance for the detection of CS-AKI. We therefore aimed at comparing these biomarkers and their kinetics (primary objective). As secondary objectives, we assessed plasma neutrophil gelatinase-associated lipocalin (pNGAL), cystatin C (pCysC) and urea (pUrea). We also determined the ability of these biomarkers to early discriminate persistent from transient CS-AKI. METHODS: Patients over 75 years-old undergoing aortic valve replacement with cardiopulmonary bypass (CPB) were included in this prospective observational study. Biomarkers were measured before/after CPB and at the sixth postoperative hour (H6). RESULTS: In 65 patients, CS-AKI occurred in 27 (42%). ∆pCr from post-CPB to H6 (∆pCrpostCPB-H6): outperformed TIMP2 IGFBP7 at H6 and its intra- or postoperative changes: area under the receiver operating characteristic curve (AUCROC) of 0.84 [95%CI:0.73-0.92] vs. ≤0.67 [95%CI:0.54-0.78], p ≤ 0.03. The AUCROC of pNGAL, pCysC and pUrea did not exceed 0.72 [95%CI:0.59-0.83]. Indexing biomarkers levels for blood or urine dilution did not improve their performance. Combining TIMP2 IGFBP7 and ∆pCrpostCPB-H6 was of no evident added value over considering ∆pCrpostCPB-H6 alone. For the early recognition of persistent CS-AKI, no biomarker outperformed ∆pCrpostCPB-H6 (AUCROC = 0.69 [95%CI:0.48-0.85]). CONCLUSIONS: In this hypothesis-generating study mostly testing early detection of mild CS-AKI, there was no evident added value of the tested modern biomarkers over early minimal postoperative changes in pCr: despite the common perioperative hemodilution in the setting of cardiac surgery, if pCr failed to decline within the 6 h after CPB, the development of CS-AKI was likely. Confirmatory studies with more severe forms of CS-AKI are required.

High prevalence of triazole resistance in Aspergillus fumigatus, especially mediated by TR/L98H, in a French cohort of patients with cystic fibrosis.

OBJECTIVES: Triazole resistance in Aspergillus fumigatus due to a single azole resistance mechanism (TR/L98H) is increasingly reported in European countries. Data from patients with cystic fibrosis (CF) are limited. Our study aimed to investigate the prevalence and molecular mechanisms of azole resistance in A. fumigatus in a cohort of patients with CF. METHODS: Eighty-five A. fumigatus isolates from 50 CF patients, collected between January 2010 and April 2011, were retrospectively analysed for azole resistance using agar plates containing 4 mg/L itraconazole. MICs of itraconazole, voriconazole and posaconazole were determined according to EUCAST methodology for each isolate able to grow on this medium. Species identification was performed by sequencing of the ß-tubulin gene. Sequencing analysis of the cyp51A gene and its promoter region was conducted. RESULTS: Nine isolates (four patients, 8% prevalence) were able to grow on itraconazole-containing agar plates. Itraconazole resistance was confirmed by EUCAST methodology (MICs >2 mg/L). All isolates had mutations in the cyp51A gene at residues previously involved in azole resistance: L98H (n = 5), M220T (n = 4) and G54R (n = 1). One patient had three genetically distinct azole-resistant isolates identified during the study. The isolates with L98H that were recovered from three patients (6% prevalence) also had the 34 bp tandem repeat in the promoter region of cyp51A (TR/L98H) and displayed multiazole resistance. CONCLUSIONS: We report an 8% prevalence of itraconazole resistance in CF patients in our centre, mostly driven by TR/L98H (6%). Our data confirm that TR/L98H occurs in France and can be highly prevalent in CF patients.

[Lipemia and bilirubin influences for twenty-four biochemical parameters measurement]. / Interférences de la lipémie et de l'ictère sur le dosage de 24 paramètres biochimiques.

The study of the influence of the lipemia and icterus was performed experimentally for twenty-four biochemistry parameters on the Roche Cobas 6000 CE analyzer. Overloads in Intralipid(®) or ditaurate of bilirubin were performed on several plasma pools. The limit of 10% was chosen to define interference on the measurement. The parameters studied were classified into different categories depending on their measurement is affected or not. Knowledge of these data allows the biologist to adapt its reporting procedures in the case of lactescent and/or icteric samples.

[Hemolysis influence on twenty-two biochemical parameters measurement]. / Interférence de l'hémolyse sur le dosage de vingt-deux paramètres biochimiques.

The study of the influence of hemolysis was determined experimentally for twenty two biochemical parameters on the analyzer Cobas 6000 ce (Roche Diagnostics). The addition method of hemolysate was used to create an increasing concentration of hemoglobin ranging from 0 to 2000 µmol/L. The limit of 10% variation was chosen to define the influence of hemolysis on the measurement. The parameters studied were classified into several categories: the parameters for which hemolysis does not influence the measurement: albumin, uric acid, calcium, C-reactive protein, myoglobin, NT -pro BNP, S100 protein, and urea; parameters impacted positively leading to an overestimation of the result: aspartate aminotransferase, total cholesterol, creatine kinase, creatinine, lactate dehydrogenase, magnesium, magnesium, total protein, triglycerides; and negatively impacted settings so causing an underestimation of the result: alanine amino- transferase, gamma glutamyl transferase, lipase, alkaline phosphatase, troponin T hypersensitive. Certain parameters influence of hemolysis varies depending on the magnitude of the measured parameter this interference being observed for normal values but disappearing for pathological values: creatinine, cholesterol, alkaline phosphatase, triglycerides, or the inverse interference is greater than for conventional pathological values: lipase, alanine amino-transferase. Knowledge of this variability interference allows the biologist to adapt its methods of reporting in the case of haemolysed samples.

[Influence of anticoagulant on the plasma level of fifteen biochemical parameters]. / Influence de la nature de l'anticoagulant sur le dosage plasmatique de quinze paramètres biochimiques.

The study of the influence of the anticoagulant used in blood collection tubes to obtain plasma was performed for fifteen biochemical parameters measured with automated Cobas 6000 (Roche Diagnostics). For each parameter tested the entire measurement domain was studied. The comparison of results obtained on plasma blood sample obtained by lithium heparin and EDTA include: correlation, the limits of acceptability in the standards of monitoring and interpretation standards regression defined by the SFBC and analysis of Bland-Altman. The parameters studied were classified into three categories. The parameters for which the assay is not influenced by the nature of the anticoagulant used: apolipoprotéin A1, apolipoprotein B, alanine amino-transferase, creatine kinase, creatinine, total cholesterol, HDL-cholesterol, lipase, NT-Pro BNP, troponine T and urea. The parameters for which the results are underestimated EDTA plasma, including those for which the impact is moderate and for which the interpretive standards are not changed: triglycerides, and those for which performance standards are changed on one or more levels: aspartate aminotransferase and lactate dehydrogenase; and finally the not practicable EDTA plasma parameters: alkaline phosphatase.

[Comparison of calculated LDL cholesterol (LDL-C) versus measured LDL cholesterol (LDL-M) and potential impact in terms of therapeutic management]. / Évaluation d'une méthode de dosage direct du LDL-cholestérol et de son impact potentiel en termes de prise en charge thérapeutique.

LDL-cholesterol value is one of the criteria used by the Haute autorité de santé (HAS) in the management of patients in primary and secondary prevention with the aim to reduce cardiovascular mortality. In this respect, the recommendations have been established based on target to achieve LDL-cholesterol. Currently in France, the determination of LDL-cholesterol is mainly carried out by the Friedewald formula whose limits are well known. However, reliable methods for the determination of LDL-cholesterol exist. We compared the results of calculated and measured LDL-cholesterol obtained from 444 patients presenting normal triglyceridemia values in terms of ranking relative to the thresholds of the HAS. The correlation between the two methods is quite good, but a significant difference (p <0.0001) was observed between the calculated and measured values of LDL-cholesterol. On the other hand in 17% of cases the classification of subjects will be different, with a majority so overestimation of calculated LDL-cholesterol with respect to measured LDL-cholesterol. This overestimation is not proportional, in fact most values measured LDL-cholesterol, the higher the calculate-measured difference is important. The rating difference is particularly important when subjects have between 1 and 3 factors of cardiovascular risk where the target LDL-cholesterol to achieve is between 1.3 and 1.9 g/L. The management of patients with lipid lowering may potentially be dependent on the method used for the determination of LDL-cholesterol.