Predictors of daytime blood pressure, nighttime blood pressure, and nocturnal dipping in patients with chronic kidney disease.

Increasing attention has recently been paid to discrepancies between office and ambulatory blood pressure (BP) control in patients with chronic kidney disease (CKD), but information on mechanisms underlying circadian BP variations in CKD remains scarce. We described circadian BP patterns and their predictors in patients with CKD stages 1 to 5 referred for kidney function testing in a French tertiary hospital: 1122 ambulatory BP measurements from 635 participants. Factors associated with daytime and nighttime systolic BP (SBP) as well as with nocturnal SBP dipping (ratio of average nighttime to daytime SBP) were analyzed with linear mixed regression models. Participants (mean age 55 ± 16 years; 36% female, mean GFR 51 ± 22 mL/min/1.73m2) had a mean daytime and nighttime SBP of 130 ± 17 and 118 ± 18 mm Hg, respectively. The prevalence of impaired dipping (nighttime over daytime SBP ratio ≥ 0.9) increased from 32% in CKD stage 1 to 68% in CKD stages 4-5. After multivariable adjustment, measured GFR, diabetes, and sub-Saharan African origin were more strongly associated with nighttime than with daytime SBP, which led to significant associations with altered nocturnal BP dipping. For a 1 SD decrease in measured GFR, nighttime BP was 2.87 mmHg (95%CI, 1.44-4.30) higher and nocturnal SBP dipping ratio was 1.55% higher (95%CI, 0.85-2.26%). In conclusion, the prevalence of impaired nocturnal BP dipping increases substantially across the spectrum of CKD. Along with sub-Saharan African origin and diabetes, lower measured GFR was a robust and specific predictor of higher nighttime BP and blunted nocturnal BP decline.

Development and validation of a new equation based on plasma creatinine and muscle mass assessed by CT scan to estimate glomerular filtration rate: a cross-sectional study.

Background: Inter-individual variations of non-glomerular filtration rate (GFR) determinants of serum creatinine, such as muscle mass, account for the imperfect performance of estimated GFR (eGFR) equations. We aimed to develop an equation based on creatinine and total lumbar muscle cross-sectional area measured by unenhanced computed tomography scan at the third lumbar vertebra. Methods: The muscle mass-based eGFR (MMB-eGFR) equation was developed in 118 kidney donor candidates (iohexol clearance) using linear regression. Validation cohorts included 114 healthy subjects from another center (51Cr-EDTA clearance, validation population 1), 55 patients with chronic diseases (iohexol, validation population 2), and 60 patients with highly discordant creatinine and cystatin C-based eGFR, thus presumed to have atypical non-GFR determinants of creatinine (51Cr-EDTA, validation population 3). Mean bias was the mean difference between eGFR and measured GFR, precision the standard deviation (SD) of the bias, and accuracy the percentage of eGFR values falling within 20% and 30% of measured GFR. Results: In validation population 1, performance of MMB-eGFR was not different from those of CKD-EPICr2009 and CKD-EPICr2021. In validation population 2, MMB-eGFR was unbiased and displayed better precision than CKD-EPICr2009, CKD-EPICr2021 and EKFC (SD of the biases: 13.1 vs 16.5, 16.8 and 15.9 mL/min/1.73 m2). In validation population 3, MMB-eGFR had better precision and accuracy {accuracy within 30%: 75.0% [95% confidence interval (CI) 64.0-86.0] vs 51.5% (95% CI 39.0-64.3) for CKD-EPICr2009, 43.3% (95% CI 31.0-55.9) for CKD-EPICr2021, and 53.3% (95% CI 40.7-66.0) for EKFC}. Difference in bias between Black and white subjects was -2.1 mL/min/1.73 m2 (95% CI -7.2 to 3.0), vs -8.4 mL/min/1.73 m2 (95% CI -13.2 to -3.6) for CKD-EPICr2021. Conclusion: MMB-eGFR displayed better performances than equations based on demographics, and could be applied to subjects of various ethnic backgrounds.

Evaluation of iron metabolism in hospitalized COVID-19 patients.

BACKGROUND: Iron metabolism dysregulation may play a role in organ failure observed in Coronavirus disease 2019 (COVID-19). This study aimed to explore the whole iron metabolism in hospitalized COVID-19 patients and evaluate the impact of tocilizumab. METHODS: We performed an observational multicentric cohort study, including patients with PCR-provenCOVID-19 from the intensive care unit (ICU) (n = 66) and medical ward (n = 38). We measured serum interleukin-6 (IL-6), ferritin, glycosylated ferritin (GF), transferrin, iron, and hepcidin. The primary outcome was death. RESULTS: Among the 104 patients, we observed decreased median GF percentage (35 %; IQ 23-51.5), low iron concentration (7.5 µmol/L; IQ 4-14), normal but low transferrin saturation (TSAT; 21%; IQ 11-33) and increased median hepcidin concentration (58.7 ng/mL; IQ 20.1-92.1). IL-6, ferritin, and GF were independently and significantly associated with death (p = 0.026, p = 0.023, and p = 0.009, respectively). Surprisingly, we observed a decorrelation between hepcidin and IL-6 concentrations in some patients. These findings were amplified in tocilizumab-treated patients. CONCLUSION: Iron metabolism is profoundly modified in COVID-19. The pattern we observed presents differences with a typical inflammation profile. We observed uncoupled IL-6/hepcidin levels in some patients. The benefit of additive iron chelation therapy should be questionable in this setting.

Clinically relevant urine creatinine underestimation in the low concentration range on the Siemens Dimension Vista®.

While considerable efforts have been accomplished to standardize the measurement of plasma creatinine (PCr), urine creatinine (UCr) has not been subject to the same scrutiny. UCr is importantly used when measuring biomarkers in spot urines, to assess urine output and variable dilution of urine samples. Here, we report underestimation of Jaffe UCr measurements on the Siemens Dimension Vista® analyzer, critically affecting samples with UCr ≤2 mmol/L. We demonstrate that this error is caused by automatic urine pre-dilution by the Vista's «urine mode¼, and that UCr measured in «plasma mode¼ without pre-dilution does not present this error. In the absence of a comprehensive solution proposed by Siemens, we propose simple formulae that can be easily implemented in a laboratory to correct these low UCr measurements. Importantly, the observed UCr underestimation can significantly influence reported results for biomarkers/UCr ratios measured in spot urine. Indeed, these results can be overestimated up to +84.4 % before correction using our formulae. This can sometimes lead to misclassification according to clinical thresholds, e.g. Kidney disease: improving global outcomes (KDIGO) guidelines for urine albumin/creatinine. This highlights the need for every clinical laboratory to assess the detection limits of their assays, including for lesser-discussed parameters such as UCr. Indeed, the error we reported here may affect other urine assays performing systematic urine pre-dilution and could have significant repercussions on the clinical management of patients.

Relationship between liver dysfunction, lipoprotein concentration and mortality during sepsis.

BACKGROUND: High-density lipoproteins (HDLs) are synthesized by the liver and display endothelioprotective properties, including anti-inflammatory, antiapoptotic, antithrombotic and antioxidant effects. In both septic and chronic liver failure patients, a low HDL cholesterol (HDL-C) concentration is associated with overmortality. Whereas sepsis-associated liver dysfunction is poorly defined, the aim of this study was to characterize the relationship between liver dysfunction, lipoprotein concentrations and mortality in septic patients in the intensive care unit (ICU). METHODS: A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, HDL-C, low-density lipoprotein-cholesterol (LDL-C), and triglyceride levels were assessed at admission. Sepsis-associated liver dysfunction was defined as a serum bilirubin≥ 2N or aspartate aminotransferase/alanine aminotransferase concentrations ≥ 2N. Short-term and one-year prognostic outcomes were prospectively assessed. RESULTS: A total of 219 septic patients were included, and 15% of them presented with sepsis-associated liver dysfunction at admission. Low concentrations of lipoproteins were associated with mortality at Day 28 in the overall population. Sepsis-associated liver dysfunction at admission was associated with overmortality. In this subgroup, patients had a lower HDL-C concentration than patients without hepatic dysfunction (HDL-C = 0.31 [0.25, 0.55] mmol/L vs. 0.48 [0.29, 0.73] mmol/L, p = 0.0079) but there was no relationship with the outcome. Interestingly, no correlation was observed between lipoprotein concentrations and liver dysfunction markers. CONCLUSION: Sepsis-associated liver dysfunction at ICU admission is strongly associated with overmortality and is associated with a lower HDL-C concentration. However, in this subgroup of patients, HDL-C concentration had no relationship with mortality. Further exploratory studies are needed to better understand the interaction between lipoproteins and liver dysfunction during sepsis.

Delayed increase of plasma selenoproteins and absence of side effect induced by infusion of pharmacological dose of sodium selenite in septic shock: Secondary analysis of a multicenter, randomized controlled trial.

BACKGROUND: In sepsis, neutrophil respiratory bursts participate in endothelium damage, the first step to multiple organ failure. In plasma two antioxidant selenoenzymes, which protect the endothelium, decrease: selenoprotein-P, and to a lesser extent glutathione peroxidase (GPX3). Sodium selenite (Na2SeO3) is a Se donor, but also an oxidant chemotherapy drug depending on its concentration. In a previous published study, Na2SeO3 continuous infusion in septic shock patients at a pharmacological dose of 4 mg1 Se/day on day-1, followed by a high nutritional dose of 1 mg Se/day during 9 days, showed no beneficial effect on weaning of catecholamine nor on survival. In this ancillary study, we report clinical and biological effects of such continuous infusion of Na2SeO3. METHODS: This was a multicenter, placebo-controlled, double-blind study on 60 patients. Na2SeO3 or placebo in continuous infusion as described above. Evolution with time of plasma Se, selenoprotein-P, GPX3, Organ dysfunction (sequential organ failure assessment SOFA scores, including PaO2/FiO2, for respiratory failure, and plasma lactate) and quality of life at 6 months (by SF36 scores) were analyzed using two-way (time, treatment) non-parametric repeated-measures analysis of variance (Friedman test). MAIN RESULTS: At baseline, plasma Se was about a quarter of reference values. From baseline to day-4 plasma Se, selenoprotein-P and GPX3 significantly increased by 3.9, 2.7 and 1.8 respectively in the Na2SeO3 group as compared with placebo and remained elevated by 2.3, 2.7 and 2.1 at day-14 respectively (p < 0.001). Na2SeO3 did not affect global and organ by organ SOFA Scores and plasma lactate concentration at day-1 and later up to day-14. The evolution of PaO2/FiO2 until day-14 was similar in the two groups. Quality of life in the surviving patients at 6 months was similar between the two groups. CONCLUSION: Continuous infusion of Na2SeO3 at 4 mg Se at day-1 seems to have neither beneficial nor toxic effect at day-1 or later and induces a late increase of selenoprotein-P at day-4. Preclinical studies are required to confirm the use of Na2SeO3 as a cytotoxic drug against neutrophils and protection of the endothelium by selenoprotein-P.

Measurement of glycosylated ferritin with Concanavalin A: Assay design, optimization and validation.

INTRODUCTION: Ferritin is the major iron-storage glycoprotein found in all tissues. Ferritin glycosylation can be assessed by the differential affinities of ferritin glycoforms for Concanavalin A (ConA), a lectin. The fraction of serum ferritin bound to ConA is called "glycosylated ferritin" (GF). Low GF reflects macrophagic activation and is an essential biomarker used in adult-onset Still's disease (AOSD), macrophage activation syndrome (MAS) and Gaucher disease diagnosis and therapeutic management. To date, no complete assay description and method validation according to the ISO 15189 standard has been published. This study aimed to describe and validate our method used for GF measurement and describe GF values observed in patients. MATERIALS AND METHODS: Ferritin glycoforms were separated based on their affinities for ConA using commercially available TRIS-barbital buffer, Sepharose and ConA/Sepharose 4B gels. Ferritin concentrations were measured on the Siemens Dimension Vista 1500®. We analysed 16,843 GF values obtained between 2000 and 2021 from our database of patients. RESULTS: Optimal separation of ferritin glycoforms was obtained by 15-min incubation of serum with ConA/Sepharose at pH 8. The optimized volume were 0.4 mL for total serum ferritin (TSF) 30-1000 µg/L and 0.5 mL for TSF 1000-2500 µg/L. Serum with higher TSF should be pre-diluted in the TRIS-barbital buffer. Reproducibility of ferritin measurement in the TRIS-barbital buffer matrix was excellent (intra-assay CV < 1%; inter-assay CV < 4%). Reproducibility of GF assay was good (intra-assay CV < 10% for low and high ferritin samples, respectively; and inter-assay CV < 10%). Inter-operator variability was 21.6% for GF < 20%. Ferritin was stable for up to 3 days in the TRIS-barbital buffer. An inter-laboratory exchange program conducted with another French hospital showed good agreement between results. In our database, <20% GF levels were scarce, compatible with the low prevalence of Still's disease, MAS, and Gaucher disease. The 95% confidence interval for GF was [26-58]%, lower than values described in the literature for healthy individuals. CONCLUSION: Thanks to good performances, this technique can become readily available for laboratories servicing patients with AOSD, MAS (including severe COVID-19 patients) and Gaucher disease patients.

Multisystem inflammatory syndrome in children: Inputs of BNP, NT-proBNP and Galectin-3.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Prognostic Role of Early Postoperative Troponin I in Lung Transplantation-A Retrospective 7-Year Analysis.

OBJECTIVES: Postoperative cardiac troponin I concentration is predictive of worsened outcomes in cardiac surgery. Lung transplantation (LT) surgery shares common features with cardiac surgery, but postoperative troponin has yet to be investigated. The authors aimed to evaluate the association between early postoperative troponin concentration and the 1-year mortality after transplantation. DESIGN: A retrospective, observational, single-center study. SETTING: At a tertiary care, university hospital. PARTICIPANTS: Patients who underwent lung transplantation from January 2011 to December 2017 INTERVENTIONS: For each patient, preoperative, intraoperative, and postoperative data were collected, as well as the troponin I measurement at the moment of postoperative intensive care unit admission. MEASUREMENTS AND MAIN RESULTS: Two hundred twenty LT procedures were analyzed. Troponin I was elevated in all LT patients, with a median of 3.82 ng/mL-1 (2-6.42) ng/mL-1 significantly higher in non-survivors than in survivors with 5.39 (2.88-7.44) v 3.50 ng/mL (1.74-5.76), p = 0.005. In the multivariate analysis, the authors found that only the Simplified Acute Physiology Score II score (hazard ratio [HR] 1.03; 95% confidence interval [CI] [1.001; 1.05]; p = 0.007) and the need to maintain extracorporeal life support at the end of surgery (HR 2.54; 95% CI [1.36; 4.73]; p = 0.003) were independently associated with the 1-year mortality. The multiple linear regression model found that troponin levels were associated with the need for extracorporeal life support (ECLS) (p = 0.014), the amount of transfused packed red blood cells (p = 0.008), and bilateral LT (p < 0.001). CONCLUSION: Early postoperative troponin serum levels were not independently associated with 1-year mortality. Early postoperative troponin I levels were correlated to bilateral LT, the need for ECLS, and intraoperative blood transfusion.

Severe Chronic Kidney Disease Is Associated with a Lower Efficiency of Bariatric Surgery.

BACKGROUND: Obesity is a risk factor for chronic kidney disease (CKD) and a relative contraindication for renal transplantation. Bariatric surgery (BS) is an option to address this issue but we hypothesize that severe CKD is associated with a loss of efficacy of BS which could justify recommending it at an earlier stage of the CKD. METHODS: A retrospective study (n = 101 patients) to test primarily for differences in weight loss at 6 and 12 months according to estimated glomerular filtration rate categories (eGFR < 30 including patients on dialysis, 30-60, 60-90, and ≥ 90 ml/min/1.73 m2) was performed with multivariate analysis adjusted for sex, age, BMI, surgical procedure, and diabetes. We used a second method to confirm our hypothesis comparing weight loss in patients with stage 4-5 CKD (eGFR < 30 ml/min/1.73 m2, n = 17), and matched controls with eGFR ≥ 90 ml/min/1.73 m2. RESULTS: In the first comparison, the multivariate analysis showed a significant positive association between eGFR and weight loss. However, after exclusion of the subgroup of patients with eGFR < 30 ml/min/1.73 m2, the difference between groups was no more significant. In addition, percent total weight loss (%TWL) was significantly lower in patients with severe CKD compared to controls: - 15% vs - 23% at 6 months (p < 0.01); - 17% vs - 27% at 12 months (p < 0.01). The percent excess weight loss at 1 year reached 47% in patients with stage 4-5 CKD and 68% in controls subjects (p < 0.01). Surgery was a success at 12 months (weight loss > 50% of excess weight) in 38% of advanced CKD and 88% of controls (p < 0.01). CONCLUSION: The efficacy of BS was reduced in patients with advanced CKD. These results support early BS in patients with early-to-moderate CKD.

Metabolic syndrome and endocrine status in HIV-infected transwomen.

BACKGROUND: HIV-infected transwomen face multiple specific issues. Economic and social marginalization, sex work, substance abuse, hormonal consumption and silicone injection may affect the course of HIV infection and lead to metabolic and endocrine complications. METHODS: A matched case-control study was performed between 2013 and 2015 in a University Hospital and compared metabolic syndrome (MetS), thyroid and adrenal functions in HIV-infected transwomen (i.e. cases) and cisgender HIV-infected men (i.e. controls) matched for age and antiretroviral therapy. The interaction between hormonal consumption, the course of HIV infection and antiretroviral therapy was also studied. Clinical and biological data (CD4 cell count, HIV RNA load, antiretroviral plasma drug concentration, HDL, triglycerides, glucose, cortisol, thyroid stimulating hormone, free thyroxine, prolactine) were measured. RESULTS: A total of 292 HIV-infected patients (100 cases and 192 controls) were prospectively included. There was no difference between the two populations in terms of frequency of MetS, but subclinical hypothyroidism and adrenal insufficiency were more frequent in cases than in controls with, respectively, 12 vs. 3% (P < 0.002) for hypothyroidism and 20 vs. 8% (P < 0.001) for adrenal insufficiency. Prolactinemia, only performed in transwomen, was often elevated (21%) but rarely confirmed as true active hyperprolactinemia (monomeric form) (3%). Although hormonal intake was frequent among transwomen (31%), no impact on antiretroviral bioavailability and efficacy was detected. CONCLUSION: In this study, no increase in the prevalence of MetS was detected in HIV-infected transwomen patients. In contrast, adrenal and thyroid functions abnormalities were frequent and should be systematically assessed in this population. No impact of hormonal intake on antiretroviral bioavailability and efficacy was detected.

Urinary proteins: up-to-date reference methods for urinary protein analysis.

Measurement of urine albumin has been introduced in the new classification of kidney disease (KD) as a marker for detecting, monitoring and predicting KD. Currently, the measure is not standardized. The variability of results obtained with commercially available procedures is important and can lead to misclassification of patients. Analytical standardization, started in 2007, is in progress. SRM 2925 primary reference material, SRM 3666 secondary reference material and liquid chromatography isotope dilution mass spectroscopy (LC-IDMS) reference measurement procedure are being validated by the National Institute of Standards and Technology (NIST). This report presents strategies and difficulties for developing this reference system.

Impact of Fetuin-A on progression of calcific aortic valve stenosis - The COFRASA - GENERAC study.

BACKGROUND: Aortic stenosis (AS) is an active disease, but the determinants of AS progression remain largely unknown. Low levels of Fetuin-A, a powerful inhibitor of ectopic calcification, have been linked to ectopic calcium tissue deposition but its role in AS progression has not been clearly evaluated. METHODS: In our ongoing prospective cohort (COFRASA/GENERAC), serum Fetuin-A level was measured at baseline and AS severity was evaluated at baseline and yearly thereafter using echocardiography (mean pressure gradient (MPG)) and computed tomography (degree of aortic valve calcification (AVC)). Annual progression was calculated as [(final measurement-baseline measurement)/follow-up duration] for both MPG and AVC measurements. RESULTS: We enrolled 296 patients (74 ±â€¯10 years,73% men); mean follow-up duration was 3.0 ±â€¯1.7 years. No correlation was found between baseline serum Fetuin-A (0.55 ±â€¯0.15 g/L) and baseline AS severity (r = 0.25, p = 0.87 for MPG; r = 0.06, p = 0.36 for AVC). More importantly, there was no correlation between baseline serum Fetuin-A level and AS progression either assessed using MPG or AVC (both r = 0.01, p = 0.82). In bivariate analysis, after adjustment for age, gender, baseline AS severity, or valve anatomy, Fetuin-A was not associated with AS progression (all p > 0.20). The absence of link with AS progression was further confirmed by the absence of link betwen serum Fetuin-A and the occurrence of AS-related events (p = 0.17). CONCLUSIONS: In a large prospective cohort of AS patients, serum Fetuin-A was not associated to hemodynamic or anatomic AS progression. Despite its capacity to inhibit ectopic calcium deposition, Fetuin-A serum level seemed to have minor influence on AS progression.

External validation and comparison of formulae estimating 24-h sodium intake from a fasting morning urine sample.

OBJECTIVE: The relationship between sodium intake and cardiovascular events is controversial, but most large epidemiological studies estimated sodium intake using formulae based on single urine samples, the validity of which is debated. We evaluated sodium intake estimating formulae in a large cohort of adult patients. DESIGN AND METHODS: Patients were asked to collect 24-h urine the day before admission. Validity of the 24-h urine collection was assessed by comparing creatinine clearance from this collection to the mean creatinine clearance from six fractionated urine samples. Only collections with creatinine clearance within ±15% of fractionated clearance were considered valid. The Kawasaki, INTERSALT and Tanaka formulae, using a morning fasting urine sample obtained upon admission, were compared with 24-h urine sodium excretion. The relationship between sodium intake, either measured or estimated, and blood pressure was assessed. RESULTS: Amongst 2278 patients referred to our physiology department between September 2006 and August 2016, 1018 had complete 24-h urine collections and were included in this analysis. Mean age was 51 ±â€Š14 years and mean sodium excretion was 3624 ±â€Š1614 mg/day. The intraclass correlation coefficient was higher for the Kawasaki (0.54; 95% confidence interval, 0.48-0.60), than for the INTERSALT (0.38; 0.33-0.42, P < 0.001), and Tanaka (0.42; 0.37-0.46, P < 0.001) formulae. The Kawasaki formula displayed the lowest mean bias (248; 157-339 mg/day). There was a significant positive association between measured sodium intake and blood pressure, and the Kawasaki formula yielded a similar association. CONCLUSION: All formulae have poor precision and accuracy and are not suitable for estimating individual sodium intake. This does not dismiss their potential value for assessment of sodium intake in population studies.

Reference change values of plasma and urine NGAL in cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: As with any biomarker, interpretation of changes of NGAL concentration must consider its variability in a specific clinical setting. The aim of this study was to calculate the reference change value (RCV) and the index of individuality (II) of plasma and urine NGAL in the context of coronary artery bypass graft surgery with cardiopulmonary bypass, in patients without postoperative acute kidney injury. METHODS: This prospective single-center observational study included patients with a preoperative glomerular filtration rate of >30mlmin-1 1.73m-2, scheduled for elective coronary artery bypass graft with cardiopulmonary bypass and free from postoperative renal injury according to KDIGO criteria during hospital stay or a plasma creatinine Δ<0 (Δ=day1-induction). Plasma and urine NGAL were measured at anesthesia induction, 4h after intensive care admission and on the first and 2nd postoperative day and normalized to plasma proteins or urine creatinine. The RCV was given by the formula: 1.96×√2×√(CVa2+CVi2), were CVi is the intra-individual variability and CVa the reported analytical coefficient of variation of 5%. The II was calculated using the formula II=CVi/CVg for the four previous parameters, where CVg is the inter-individual variability. RESULTS: Of the 100 patients enrolled in the study, 73 or 25 were considered free from acute kidney injury (KDIGO and Δ creatinine criteria, respectively) and included in the analysis. The RCV was 104% and 109% for plasma NGAL and 321% and 608% for urine NGAL. The II was <0.6 for both plasma and urine NGAL. CONCLUSIONS: In patients who underwent coronary artery bypass grafting with normal post-operative kidney function, two-fold change in plasma NGAL and three to six-fold change in urine NGAL occur. In this specific clinical context, pathological variations must consider this biological "noise" for correct interpretation.

Diagnostic Performance of C-Reactive Protein in Detecting Post-Operative Infectious Complications After Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Gastric leak is the most common and dreaded post-operative infectious complication (PIC) after laparoscopic sleeve gastrectomy (LSG). Accurate identification of patients at risk postoperatively is of cardinal importance. OBJECTIVE: The aim of this study is to assess the diagnostic performance of C-reactive protein (CRP) in predicting PICs and the most optimal time to measure it. METHODS: CRP results were collected in patients undergoing LSG between 2011 and 2015. CRP was systematically measured on post-operative days (POD) 1, 3, and 5. RESULTS: Of 1326 patients, 42 (3.2%) developed a PIC at a median of 5 days after surgery. The incidence of leakage was 1.9%. The best area under the curve was observed on POD5 (0.87; 95% CI 0.77-0.96). At this time point, a cut-off of 115 mg/L yielded a sensitivity of 66.7% (95% CI 46.5-86.8%), a specificity of 95.1% (95% CI 93.9-96.3%), a positive and negative predictive values of 19.4% (95% CI 10.3-28.6%) and 99.4% (95% CI 99.0-100%), respectively, and a positive and negative likelihood ratios (LRs) of 13.62 and 0.35, respectively. The combination of sequential assessments of CRP on POD3 and 5 provided a sensitivity of 84.4% (95% CI 71.8-97.0%), a specificity of 91.1% (95% CI 89.5-92.8%), a positive and negative predictive values of 20.9% (95% CI 14.0-27.9%) and 99.5% (95% CI 99.1-99.9%), respectively, and a positive and a negative LRs of 9.58 and 0.17, respectively. CONCLUSIONS: CRP may be useful to identify patients at risk of PICs after LSG and, therefore, to prompt early investigation. However, CRP does not help rule out PICs.

Multicenter Evaluation of Cystatin C Measurement after Assay Standardization.

BACKGROUND: Since 2010, a certified reference material ERM-DA471/IFCC has been available for cystatin C (CysC). This study aimed to assess the sources of uncertainty in results for clinical samples measured using standardized assays. METHODS: This evaluation was performed in 2015 and involved 7 clinical laboratories located in France and Belgium. CysC was measured in a panel of 4 serum pools using 8 automated assays and a candidate isotope dilution mass spectrometry reference measurement procedure. Sources of uncertainty (imprecision and bias) were evaluated to calculate the relative expanded combined uncertainty for each CysC assay. Uncertainty was judged against the performance specifications derived from the biological variation model. RESULTS: Only Siemens reagents on the Siemens systems and, to a lesser extent, DiaSys reagents on the Cobas system, provided results that met the minimum performance criterion calculated according to the intraindividual and interindividual biological variations. Although the imprecision was acceptable for almost all assays, an increase in the bias with concentration was observed for Gentian reagents, and unacceptably high biases were observed for Abbott and Roche reagents on their own systems. CONCLUSIONS: This comprehensive picture of the market situation since the release of ERM-DA471/IFCC shows that bias remains the major component of the combined uncertainty because of possible problems associated with the implementation of traceability. Although some manufacturers have clearly improved their calibration protocols relative to ERM-DA471, most of them failed to meet the criteria for acceptable CysC measurements.

Associations between serum lipids and breast cancer incidence and survival in the E3N prospective cohort study.

PURPOSE: Several mechanistic studies support a role of cholesterol or its metabolites in breast cancer etiology, but associations have been inconsistent in epidemiological studies. In observational studies, possible reverse causation must be accounted for using a prospective design. We investigated prospective associations between pre-diagnostic serum lipid concentrations [total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides], and both breast cancer risk and survival in the E3N cohort study. METHODS: Analyses were performed on 583 cases from the E3N prospective cohort diagnosed between 1994 and 2005, and 1,043 controls matched on date, age, recruitment center and menopausal status at blood collection. Odds ratios (OR) and 95% confidence intervals were estimated using conditional logistic regression. Risks of recurrence were estimated among cases using Cox proportional hazards model. Models were adjusted for lifestyle risk factors and mutually adjusted for lipid concentrations. Survival analyses were additionally adjusted for tumor characteristics. RESULTS: Overall, there was no association between any serum lipid and breast cancer risk or survival. In stratified analyses, statistically significant interaction was observed between TC and menopausal status (P interaction = 0.05) and between TC and waist circumference (P interaction = 0.03), although the ORs did not reach statistical significance in any of the strata. There was no statistically significant effect modification by BMI, time between blood donation and diagnosis or ER status. CONCLUSIONS: Our results suggest that serum lipids are not associated with breast cancer risk overall, but that menopausal status and waist circumference should be considered in further studies.