Liège, Belgium
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Vieira M.C.,Pontifical University of Parana | Miyague N.I.,Pontifical University of Parana | Van Steen K.,Montefiore Institute | Salvatore S.,University of Insubria | Vandenplas Y.,UZ BRUSSEL
Acta Paediatrica, International Journal of Paediatrics | Year: 2012

Aim: To prospectively evaluate the effects of oral domperidone on the QTc interval in infants. Methods: Infants (0-1 year) with a diagnosis of gastro-oesophageal reflux (GOR) disease were included. A 12-lead electrocardiography (ECG) was performed in all infants at baseline and 1 h after the intake of domperidone after 7-14 days; the corrected QTc interval was calculated by one investigator (MV) according to Bazett's formula. Results: Forty-five infants were enroled in this study. The mean gestational age was of 38.6 weeks (35.5-42.0), and the mean age at the start of domperidone was 75.3 days (19-218 days). No statistically significant difference in corrected QTc was observed between baseline and the second ECG (0.389 ± 0.02 vs. 0.397 ± 0.31; p 0.130)). A trend was observed regarding gender: Although there was no difference in QTc change in girls (p 0.622), there was a strong trend in boys (p 0.051). Two infants (both boys) had a clinically significant QTc prolongation (>460 msec) without symptoms. The Spearman correlation test showed no relation between the QTc change and age (r: -0.05822; p 0.7284). There was no relation between domperidone dosage and QTc change. Conclusion: Overall, the group-analysis showed no statistical significant difference in QTc duration induced by domperidone. However, 2/45 (4.4%) infants had a prolonged QTc interval (>460 msec) induced by domperidone. As a consequence, QTc measurement should be recommended in routine in infants when domperidone is started. © 2012 The Author(s)/Acta Pædiatrica.


De Greef E.,Queen Paola Childrens Hospital | Mahachie John J.M.,Montefiore Institute | Hoffman I.,Pediatric Gastroenterology | Smets F.,Catholic University of Leuven | And 22 more authors.
Journal of Crohn's and Colitis | Year: 2013

Aim: A Belgian registry for pediatric Crohn's disease, BELCRO, was created. This first report aims at describing disease presentation and phenotype and determining associations between variables at diagnosis and registration in the database. Methods: Through a collaborative network, children with previously established Crohn's disease and newly diagnosed children and adolescents (under 18. y of age) were recruited over a 2. year period. Data were collected by 23 centers and entered in a database. Statistical association tests analyzed relationships between variables of interest at diagnosis. Results: Two hundred fifty-five patients were included. Median age at diagnosis was 12.5. y (range: 1.6-18. y); median duration of symptoms prior to diagnosis was 3. m (range: 1-12. m). Neonatal history and previous medical history did not influence disease onset nor disease behavior. Fifty three % of these patients presented with a BMI z-score < - 1. CRP was an independent predictor of disease severity. Steroids were widely used as initial treatment in moderate to severe and extensive disease. Over time, immunomodulators and biological were prescribed more frequently, reflecting a lower prescription rate for steroids and 5-ASA. A positive family history was the sole significant determinant for earlier use of immunosuppression. Conclusion: In Belgium, the median age of children presenting with Crohn's disease is 12.5. y. Faltering growth, extensive disease and upper GI involvement are frequent. CRP is an independent predictive factor of disease activity. A positive family history appears to be the main determinant for initial treatment choice. © 2013 European Crohn's and Colitis Organisation.


Maury G.,Catholic University of Leuven | Cambron L.,University of Sfax | Jamart J.,Catholic University of Leuven | Marchand E.,Catholic University of Leuven | And 2 more authors.
Journal of Sleep Research | Year: 2013

In-laboratory polysomnography is the 'gold standard' for diagnosing obstructive sleep apnea syndrome, but is time consuming and costly, with long waiting lists in many sleep laboratories. Therefore, the search for alternative methods to detect respiratory events is growing. In this prospective study, we compared attended polysomnography with two other methods, with or without mandible movement automated analysis provided by a distance-meter and added to airflow and oxygen saturation analysis for the detection of respiratory events. The mandible movement automated analysis allows for the detection of salient mandible movement, which is a surrogate for arousal. All parameters were recorded simultaneously in 570 consecutive patients (M/F: 381/189; age: 50±14years; body mass index: 29±7kgm-2) visiting a sleep laboratory. The most frequent main diagnoses were: obstructive sleep apnea (344; 60%); insomnia/anxiety/depression (75; 13%); and upper airway resistance syndrome (25; 4%). The correlation between polysomnography and the method with mandible movement automated analysis was excellent (r: 0.95; P<0.001). Accuracy characteristics of the methods showed a statistical improvement in sensitivity and negative predictive value with the addition of mandible movement automated analysis. This was true for different diagnostic thresholds of obstructive sleep severity, with an excellent efficiency for moderate to severe index (apnea-hypopnea index ≥15h-1). A Bland & Altman plot corroborated the analysis. The addition of mandible movement automated analysis significantly improves the respiratory index calculation accuracy compared with an airflow and oxygen saturation analysis. This is an attractive method for the screening of obstructive sleep apnea syndrome, increasing the ability to detect hypopnea thanks to the salient mandible movement as a marker of arousals. © 2012 European Sleep Research Society.


de Greef E.,Queen Paola Childrens Hospital | Hoffman I.,Pediatric gastroenterology | D'Haens G.,Imelda Hospital | van Biervliet S.,Pediatric gastroenterology | And 17 more authors.
Acta Gastro-Enterologica Belgica | Year: 2012

Biologicals have become an important component in the treatment of Crohn's disease in children. Their increased and long term use raises safety concerns. We describe safety and cost of infliximab in Belgian pediatric Crohn's disease patients. All patients on infliximab as part of the present or past treatment for Crohn's Disease until January 1st 2011 were selected from an existing database. Information on disease phenotype, medication and adverse events were extracted. Adverse events occurred in 25.9% of patients exposed to infliximab of which 29.6% were severe. In total 31.7% of patients stopped infliximab therapy. The main reasons for discontinuation were adverse events in 45.4% and loss of response in 30.3%. No malignancies or lethal complications occurred over this 241 patient year observation period. Immuno - modulators were concomitant medication in 75% of patients and were discontinued subsequently in 38.4% of them. The cost of infliximab infusions per treated patient per year in the Belgian health care setting is approximately 9 474 euro, including only medication and hospital related costs. Even though infliximab is relatively safe in pediatric CD on the short term, close follow-up and an increased awareness of the possible adverse reactions is highly recommended. Adverse reactions appeared in 25.9% of all patients and were the main reason for discontinuation. Treatment cost has to be balanced against efficacy and modifications in disease course. In the Belgian health care system, the medication is available to all patients with moderate to severe CD.


Pineda S.,Genetic and Molecular Epidemiology Group | Pineda S.,Montefiore Institute | Real F.X.,Epithelial Carcinogenesis Group | Real F.X.,University Pompeu Fabra | And 6 more authors.
PLoS Genetics | Year: 2015

Omics data integration is becoming necessary to investigate the genomic mechanisms involved in complex diseases. During the integration process, many challenges arise such as data heterogeneity, the smaller number of individuals in comparison to the number of parameters, multicollinearity, and interpretation and validation of results due to their complexity and lack of knowledge about biological processes. To overcome some of these issues, innovative statistical approaches are being developed. In this work, we propose a permutation-based method to concomitantly assess significance and correct by multiple testing with the MaxT algorithm. This was applied with penalized regression methods (LASSO and ENET) when exploring relationships between common genetic variants, DNA methylation and gene expression measured in bladder tumor samples. The overall analysis flow consisted of three steps: (1) SNPs/CpGs were selected per each gene probe within 1Mb window upstream and downstream the gene; (2) LASSO and ENET were applied to assess the association between each expression probe and the selected SNPs/CpGs in three multivariable models (SNP, CPG, and Global models, the latter integrating SNPs and CPGs); and (3) the significance of each model was assessed using the permutation-based MaxT method. We identified 48 genes whose expression levels were significantly associated with both SNPs and CPGs. Importantly, 36 (75%) of them were replicated in an independent data set (TCGA) and the performance of the proposed method was checked with a simulation study. We further support our results with a biological interpretation based on an enrichment analysis. The approach we propose allows reducing computational time and is flexible and easy to implement when analyzing several types of omics data. Our results highlight the importance of integrating omics data by applying appropriate statistical strategies to discover new insights into the complex genetic mechanisms involved in disease conditions. © 2015 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication


PubMed | Genetic and Molecular Epidemiology Group, Hospital Universitario Ramon y Cajal, Epithelial Carcinogenesis Group, Montefiore Institute and 2 more.
Type: Journal Article | Journal: PLoS genetics | Year: 2015

Omics data integration is becoming necessary to investigate the genomic mechanisms involved in complex diseases. During the integration process, many challenges arise such as data heterogeneity, the smaller number of individuals in comparison to the number of parameters, multicollinearity, and interpretation and validation of results due to their complexity and lack of knowledge about biological processes. To overcome some of these issues, innovative statistical approaches are being developed. In this work, we propose a permutation-based method to concomitantly assess significance and correct by multiple testing with the MaxT algorithm. This was applied with penalized regression methods (LASSO and ENET) when exploring relationships between common genetic variants, DNA methylation and gene expression measured in bladder tumor samples. The overall analysis flow consisted of three steps: (1) SNPs/CpGs were selected per each gene probe within 1Mb window upstream and downstream the gene; (2) LASSO and ENET were applied to assess the association between each expression probe and the selected SNPs/CpGs in three multivariable models (SNP, CPG, and Global models, the latter integrating SNPs and CPGs); and (3) the significance of each model was assessed using the permutation-based MaxT method. We identified 48 genes whose expression levels were significantly associated with both SNPs and CPGs. Importantly, 36 (75%) of them were replicated in an independent data set (TCGA) and the performance of the proposed method was checked with a simulation study. We further support our results with a biological interpretation based on an enrichment analysis. The approach we propose allows reducing computational time and is flexible and easy to implement when analyzing several types of omics data. Our results highlight the importance of integrating omics data by applying appropriate statistical strategies to discover new insights into the complex genetic mechanisms involved in disease conditions.


PubMed | University Hospital Leuven, Catholic University of Leuven, Ghent University and Montefiore Institute
Type: Journal Article | Journal: Gut | Year: 2015

Pouchitis is the most common complication after colectomy with ileal pouch-anal anastomosis (IPAA) for UC and the risk is the highest within the 1st year after surgery. The pathogenesis is not completely understood but clinical response to antibiotics suggests a role for gut microbiota. We hypothesised that the risk for pouchitis can be predicted based on the faecal microbial composition before colectomy.Faecal samples from 21 patients with UC undergoing IPAA were prospectively collected before colectomy and at predefined clinical visits at 1 month, 3 months, 6 months and 12months after IPAA. The predominant microbiota was analysed using community profiling with denaturing gradient gel electrophoresis followed by quantitative real-time PCR validation.Cluster analysis before colectomy distinguished patients with pouchitis from those with normal pouch during the 1st year of follow-up. In patients developing pouchitis, an increase of Ruminococcus gnavus (p<0.001), Bacteroides vulgatus (p=0.043), Clostridium perfringens (p=0.011) and a reduction of two Lachnospiraceae genera (Blautia (p=0.04), Roseburia (p=0.008)) was observed. A score combining these five bacterial risk factors was calculated and presence of at least two risk factors showed a sensitivity and specificity of 100% and 63.6%, respectively.Presence of R. gnavus, B. vulgatus and C. perfringens and absence of Blautia and Roseburia in faecal samples of patients with UC before surgery is associated with a higher risk of pouchitis after IPAA. Our findings suggest new predictive and therapeutic strategies in patients undergoing colectomy with IPAA.


Darbois Texier B.,Grasp | Laurent P.,Montefiore Institute | Stoukatch S.,Montefiore Institute | Dorbolo S.,Grasp
Microfluidics and Nanofluidics | Year: 2016

This study considers the spreading of a Newtonian and perfectly wetting liquid in a square array of cylindric micropillars confined between two plates. We show experimentally that the dynamics of the contact line follows a Washburn-like law which depends on the characteristics of the micropillar array (height, diameter and pitch). The presence of pillars can either enhance or slow down the motion of the contact line. A theoretical model based on capillary and viscous forces has been developed in order to rationalize our observations. Finally, the impact of pillars on the volumic flow rate of liquid which is pumped in the microchannel is inspected. © 2016, Springer-Verlag Berlin Heidelberg.


Maree R.,GIGA Bioinformatics Core Facility | Maree R.,GIGA Research | Maree R.,Montefiore Institute | Rollus L.,GIGA Research | And 11 more authors.
2014 IEEE 11th International Symposium on Biomedical Imaging, ISBI 2014 | Year: 2014

We present a novel methodology combining web-based software development practices, machine learning, and spatial databases for computer-aided quantification of regions of interest (ROIs) in large-scale imaging data. We describe our main methodological choices, and then illustrate the benefits of the approach (workload reduction, improved precision, scalability, and traceability) on hundreds of whole-slide images of biological tissue slices in cancer research. © 2014 IEEE.


Muguerra H.,University of Liège | Rivas-Murias B.,University of Liège | Rivas-Murias B.,University of Santiago de Compostela | Traianidis M.,Belgian Ceramic Research Center | And 5 more authors.
Journal of Alloys and Compounds | Year: 2011

We report the high temperature thermoelectric properties of Ca 1-xDyxMn1-yNbyO3-δ (x = 0, 0.02, 0.1 and y = 0, 0.02) synthesized by spray-drying method. A maximum power factor (PF) value of 2.65 μW K-2 cm-1 is obtained at 1100 K for CaMn0.98Nb0.02O 3-δ. This represents an improvement of about 75% with respect to undoped CaMnO3-δ sample at the same temperature. We also provide a complete structural characterization of the samples. © 2011 Elsevier B.V. All Rights Reserved.

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