Kortrijk, Belgium
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Borbath I.,Cliniques Universitaires Saint Luc Bruxelles | Ceratti A.,Cliniques Universitaires Saint Luc Bruxelles | Verslype C.,University Hospital Leuven | Demols A.,Hepato Gastroenterology and Gastro Intestinal Oncology Unit | And 8 more authors.
Annals of Oncology | Year: 2013

Background: Cholangiocarcinomas are uncommon tumours with a poor prognosis, that frequently present epidermal growth factor receptor overexpression. Methods: In a multi-centre phase II trial, patients with unresectable cholangiocarcinoma, naïve to chemotherapy, received Cetuximab (400 mg/m2 at week 1, then 250 mg/m2/week) and Gemcitabine (1 g/m2 on day 1, 8 and 15 every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months, using a Simon 2-stage design. Moreover, we assessed the impact of KRAS status and skin toxic effect on efficacy. Results: Forty-four patients (41% locally advanced/59% metastatic) were enrolled. Median age was 61.5 years; ECOG PS was 0 (68%) or 1. Six months PFS reached 47%. Median OS was 13.5 months [95% confidence interval (CI) 9.8-31.8 months]. Nine patients (20.4%) had PR and disease-control rate was 79.5%. Grade 3/4-related toxic effects were haematological (52.2%), skin rash (13.6%) and fatigue (11.4%). KRAS mutations were found in 7 of 27 patients and had no influence on PFS. Skin toxic effect =grade 2 was associated with increased PFS (P = 0.05).Conclusion(s): Our study met its primary end point, suggesting that Gemcitabine-Cetuximab has activity in cholangiocarcinoma. KRAS status was not associated with PFS, unlike skin toxic effect, which could be used as a surrogate marker for efficacy. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology All rights reserved.


Briot K.,University of Paris Descartes | Durnez A.,University of Paris Descartes | Durnez A.,AZ Groeninge Hospital | Paternotte S.,University of Paris Descartes | And 3 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objectives: To assess bone mineral density (BMD) at lumbar spine and hip in a large cohort of patients with early inflammatory back pain (IBP) suggestive of axial spondyloarthritis (SpA), and to assess systemic and bone inflammation (according to MRI) as risk factors of low BMD. Patients and Methods: 332 (52.4% male) patients with IBP suggestive of axial SpA defined by Calin or Berlin criteria were recruited; they had lumbar spine and hip BMD and body composition measurements. Low BMD was defined by Z≤-2 (at least one site). Clinical, biological (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) and imaging (x-rays, spine and sacroiliac joint MRI) parameters were compared in patients with and without low BMD (Z≤-2). Significant parameters in univariate analysis were tested in multivariate models. Results: Patients (mean age 33.8 years) had a short duration of axial symptoms (mean 1.6 years); 71.4% fulfilled the Assessment of Spondyloarthritis International Society criteria for axial SpA and HLA-B27 was present in 62.1%. 43 (13.0%) had low BMD (88% male). Multivariate logistic regression showed that parameters significantly associated with low BMD (any site) were the presence of bone marrow oedema (inflammatory lesions) on MRI (OR 4.63, p=0.001), either ESR or CRP (OR 2.60, p=0.037) and male gender (OR 9.60, p=0.0004). Conclusions: This study conducted in a large cohort of young adults with early IBP suggestive of SpA shows that 13.0% of patients have a low BMD and that the main risk factor associated with low BMD was inflammation on MRI.


Cooreman S.,AZ Groeninge Hospital | Deprez C.,AZ Groeninge Hospital | Martens F.,AZ Groeninge Hospital | Van Bocxlaer J.,Ghent University | Croes K.,AZ Groeninge Hospital
Journal of Separation Science | Year: 2010

Fentanyl, norfentanyl, alfentanil, sufentanil, remifentanil and 3-methylfentanyl are potent, short-acting, synthetic narcotic analgesics that are not revealed in standard opiate immunoassays. In this article, a fully validated analytical method for the determination of these fentanyl-type compounds in plasma and urine is presented, consisting of a liquid-liquid extraction followed by a LC-MS/MS analysis using electrospray ionisation in the positive ionisation mode. Fentanyl-d5 and norfentanyl-d5 were used as internal standards. The lower LOQ in plasma and urine was 0.1 ng/mL for fentanyl, norfentanyl, alfentanil, remifentanil and 3-methylfentanyl, and 0.2 ng/mL for sufentanil. The method proved linear over a concentration range of 0.2-50 ng/mL for sufentanil and 0.1-50 ng/mL for all other analytes, with correlation coefficients of 0.998 or better. The analytical procedure showed excellent selectivity and precision (all CVs below 15%) for all analytes. Accuracy was good, except for sufentanil, where deviations of more than 15% from nominal concentrations were observed. No matrix effects were observed, and stability of stock and internal standard solutions was within acceptability limits. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.


Hoecke F.V.,Sint Andries Hospital of Tielt | Beuckelaers E.,Sint Andries Hospital of Tielt | Lissens P.,Sint Andries Hospital of Tielt | Boudewijns M.,AZ Groeninge Hospital
Journal of Clinical Microbiology | Year: 2013

We describe the first case of bacteremia due to Actinomyces urogenitalis. Bacteremia was secondary to a tubo-ovarian abscess following transvaginal oocyte retrieval. Identification was established by matrix-assisted desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and confirmed by 16S rRNA gene sequencing. A. urogenitalis should be considered as a potential causative agent of infection after gynecological procedures. Copyright © 2013, American Society for Microbiology. All Rights Reserved.


Hoste E.A.J.,Ghent University | Hoste E.A.J.,Research Foundation Flanders | De Corte W.,AZ Groeninge Hospital
Current Opinion in Critical Care | Year: 2013

PURPOSE OF REVIEW: Acute kidney injury (AKI) is a frequent finding in critically ill patients and is associated with adverse outcomes. With the purpose of improving outcome of AKI, the Kidney Disease: Improving Global Outcomes (KDIGO) group, a group of experts in critical care nephrology, has presented a set of guidelines in 2012, based on the evidence gathered until mid 2011. This review will update these guidelines with recent evidence. RECENT FINDINGS: Early application of a set of therapeutic measures - a bundle - is advised for the prevention and therapy of AKI. Hemodynamic optimization remains the cornerstone of prevention and treatment of AKI. Fluid resuscitation should be with isotonic crystalloids. Recent evidence demonstrated a higher risk for renal replacement therapy (RRT) and mortality in hydroxyethyl starch-exposed patients. Further, blood pressure should be maintained by the use of vasopressors in vasomotor shock. Nephrotoxic drugs should be avoided or stopped when possible. Contrast-associated AKI should be prevented by prehydration with either NaCl 0.9% or a bicarbonate solution. Other therapies, including intravenous N-acetylcysteine and hemofiltration are not recommended. Optimal timing of RRT remains controversial. Fluid overload remains an important determinant for the initiation of RRT. Continuous therapies are preferred in hemodynamically unstable patients; otherwise, choice of modality does not impact on outcomes. SUMMARY: The KDIGO guidelines as presented in 2012 provide guidelines on the domain of definition of AKI, prevention and treatment, contrast-induced AKI and dialysis interventions for AKI. Especially, early application of a set of measures, the AKI bundle, may prevent AKI and improve outcome. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Hoste L.,Catholic University of Leuven | Deiteren K.,AZ Groeninge Hospital | Pottel H.,Catholic University of Leuven | Callewaert N.,AZ Groeninge Hospital | Martens F.,AZ Groeninge Hospital
BMC Nephrology | Year: 2015

Background: The first aim of the study was to investigate the accuracy and intra-laboratory variation of serum creatinine measurements in clinical laboratories in Flanders. The second purpose was to check the effect of this variation in serum creatinine concentration results on the calculated estimated glomerular filtration rate (eGFR) and the impact on classification of patients into a chronic kidney disease (CKD) stage. Methods: 26 routine instruments were included, representing 13 different types of analyzers from 6 manufacturers and covering all current methodologies (Jaffe, compensated Jaffe, enzymatic liquid and dry chemistry methods). Target values of five serum pools (creatinine concentrations ranging from 35 to 934 μmol/L) were assigned by the gold standard method (ID-GC/MS). Results: Intra-run CV (%) (n = 5) and bias (%) from the target values were higher for low creatinine concentrations. Especially Jaffe and enzymatic dry chemistry methods showed a higher error. The calculated eGFR values corresponding with the reported creatinine concentration ranges resulted in a different CKD classification in 47% of cases. Conclusions: Although most creatinine assays claim to be traceable to the gold standard (ID-GC/MS), large inter-assay differences still exist. The inaccuracy in the lower concentration range is of particular concern and may lead to clinical misinterpretation when the creatinine-based eGFR of the patient is used for CKD staging. Further research to improve harmonization between methods is required. © 2015 Hoste et al.


Pottel H.,The Interdisciplinary Center | Hoste L.,The Interdisciplinary Center | Martens F.,AZ Groeninge Hospital
Clinica Chimica Acta | Year: 2010

Background: The MDRD Study equation is the most popular equation for estimating the glomerular filtration rate (eGFR) from serum creatinine (Scr), age, sex and race. Many articles deal with ethnic factors, correcting the MDRD Study equation for different populations, with more or less success. The new CKD-EPI equation introduced the concept of a population-normalized Scr in the eGFR equation for white men (Scr/0.90) and white women (Scr/0.70). Methods: We introduce alternative mathematical forms for the MDRD Study equation and the CKD-EPI equation, using the concept of a population-normalized Scr, resulting in a more general and mathematically less complicated form for the eGFR equation. Results: We show that the normalization constant corresponds to the mean Scr-value for the specific healthy population. We compared the established equations with the new alternative forms, and show that the differences are minimal. The sex/race dependency is completely comprehended in the normalization constant, making the alternative eGFR equations independent of sex and race. Conclusion: The age-dependency of eGFR remains and consequently age-dependent cutoff values for the classification of Chronic Kidney Disease (CKD) look more appropriate, contrary to the current classification rules. The population-normalized Scr which is independent of age, sex and race may serve as an alternative for the classification of CKD. © 2010 Elsevier B.V.


Pottel H.,Catholic University of Leuven | Mottaghy F.M.,University Hospital | Mottaghy F.M.,RWTH Aachen | Zaman Z.,University Hospital | Martens F.,AZ Groeninge Hospital
Pediatric Nephrology | Year: 2010

The Schwartz formula (eGFR = kL/Scr, with k = 0.55) to determine the estimated glomerular filtration rate (eGFR) in children with chronic kidney disease (CKD), based on length (L) and serum creatinine (Scr) has recently been updated for enzymatic serum creatinine concentrations, resulting in k = 0.413. Based on a meta-analysis, we evaluated the validity of this updated equation and other published equations for healthy children. This is the first time that publicly available data for healthy children of uncorrected and body surface area (BSA)-corrected median GFR have been combined with median serum creatinine values and median lengths and weights from different sources in the literature to evaluate several statistical models to estimate GFR in children. For enzymatic serum creatinine, we show that the simple model for uncorrected GFR (uGFR = k′L3/Scr, with k′ = 1.32 × 10-5) and the BSA-corrected GFR (cGFR = kL/Scr, analogous to the Schwartz formula), with an important age-dependent adaptation for k (k= 0.0414× ln (Age) + 0. 301), correlate extremely well with chromium-51-ethylenediamine tetra-acetic acid (51Cr-EDTA) data for children between 1 month and 14 years of age. With this age-dependent modification for k, presented here, the simple bedside calculation tool derived by Schwartz can be used for screening all children for CKD. When height information is not available, the Lund-Malmö equation is an excellent alternative. © 2009 IPNA.


Pottel H.,The Interdisciplinary Center | Hoste L.,The Interdisciplinary Center | Delanaye P.,University of Liège | Cavalier E.,University of Liège | Martens F.,AZ Groeninge Hospital
Clinica Chimica Acta | Year: 2012

Background: The recent evaluation of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for estimating the glomerular filtration rate (GFR) in multiple ethnicities has raised the question on how well this equation performs for African-American and Asian subjects. There is no doubt that serum creatinine (Scr) concentration differs between ethnicities and sexes. We show that creatinine-based equations for white populations may be inaccurate for estimating GFR in other ethnic/gender groups, especially in populations from Asia. Methods: This study presents a mathematical analysis of the CKD-EPI-equation complemented with a literature review of median and reference values for IDMS-standardized Scr-concentrations for multiple ethnicities. Results: The study shows that at equal eGFR-CKD-EPI-values, the ratio of Scr between females and males equals 0.79 and between other ethnicities/sexes and white males is constant too. From this information, it is possible to calculate mean Scr-values that correspond very well with literature values directly obtained from Scr-distributions in healthy white males and females and in black males, but the discrepancy is larger for other populations. Conclusions: Our results confirm the criticism that has been raised for using the CKD-EPI-equation for these ethnicities. An alternative eGFR-model is proposed based on a population-normalized Scr that needs further validation. © 2012 Elsevier B.V.


Pottel H.,The Interdisciplinary Center | Hoste L.,The Interdisciplinary Center | Martens F.,AZ Groeninge Hospital
Pediatric Nephrology | Year: 2012

Background The chronic kidney disease (CKD) classification system for children is similar to the CKD classification system for adults, using estimated glomerular filtration rate (eGFR) combined with fixed cut-off values of 60, 30, and 15 ml/min/1.73 m 2 for CKD stages III, IV, and V, respectively. To estimate GFR in children, eGFR-equations are used that require serum creatinine (Scr), but also height information, which is normally not available in clinical laboratory databases. Methods This retrospective study is based on data from two different databases, one that has previously been used to develop the Flanders Metadata equation for children and one database including 353 children who underwent 51Cr-EDTA GFR, serum creatinine, height, and weight measurements. Results A height-independent eGFR equation based on the concept of a population-normalized Scr, presented before for adults, is extended to children: eGFR0107.3/(Scr/Q), with Q the median Scr for healthy children of a particular age. This equation is validated against direct measurements of GFR, and against the updated Schwartz and Flanders Metadata equation. Conclusions The new simple height-independent equation performs very well and should make (mass) screening of kidney function in children easier. © IPNA 2012.

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