References of "Louis, Edouard"
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See detailMacrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p
GUIOT, Julien ULiege; Cambier, Maureen ULiege; Boeckx, Amandine ULiege et al

in Thorax (2020)

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology and cure. Recent studies have reported a dysregulation of exosomal microRNAs ... [more ▼]

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology and cure. Recent studies have reported a dysregulation of exosomal microRNAs (miRs) in the IPF context. However, the impact of IPF-related exosomal miRs on the progression of pulmonary fibrosis is unknown. Methods: Two independent cohorts were enrolled at the ambulatory care polyclinic of Liège University. Exosomes from sputum were obtained from 19 patients with IPF and 23 healthy subjects (HSs) (cohort 1), and the ones from plasma derived from 14 patients with IPF and 14 HSs (cohort 2). Exosomal miR expression was performed by quantitative reverse transcription–PCR. The functional role of exosomal miRs was assessed in vitro by transfecting miR mimics in human alveolar epithelial cells and lung fibroblasts. Results: Exosomal miR analysis showed that miR-142-3p was significantly upregulated in sputum and plasma of patients with IPF (8.06-fold, p<0.0001; 1.64 fold, p=0.008, respectively). Correlation analysis revealed a positive association between exosomal miR-142-3p and the percentage of macrophages from sputum of patients with IPF (r=0.576, p=0.012), suggesting macrophage origin of exosomal miR-142-3p upregulation. The overexpression of miR-142-3p in alveolar epithelial cells and lung fibroblasts was able to reduce the expression of transforming growth factor β receptor 1 (TGFβ-R1) and profibrotic genes. Furthermore, exosomes isolated from macrophages present antifibrotic properties due in part to the repression of TGFβ-R1 by miR-142-3p transfer in target cells. Discussion: Our results suggest that macrophage-derived exosomes may fight against pulmonary fibrosis progression via the delivery of antifibrotic miR-142–3 p to alveolar epithelial cells and lung fibroblasts. [less ▲]

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See detailSpecificity of metabolic colorectal cancer biomarkers in serum through effect size
Di Giovanni, Nicolas ULiege; MEUWIS, Marie-Alice ULiege; LOUIS, Edouard ULiege et al

in Metabolomics (2020), 16(8),

Introduction: Colorectal cancer is one of the most diagnosed cancers, leading to numerous deaths. In addition to existing screening methods, metabolic profiling could help both to diagnose and to ... [more ▼]

Introduction: Colorectal cancer is one of the most diagnosed cancers, leading to numerous deaths. In addition to existing screening methods, metabolic profiling could help both to diagnose and to understand the various states of the disease. Objectives: Find specific candidate biomarkers (CB) in serum of patients with colorectal cancer (CRC), in comparison to the situation after remission (R-CRC), evaluated on distinct patients. Methods: All serum samples were analyzed using comprehensive two-dimensional gas chromatography (GC × GC) coupled to high resolution time of flight mass spectrometry (TOF-MS) through an optimized and validated untargeted analytical method regulated by a quality control (QC) system. First, we used a specific multi-approaches data (pre)processing workflow to highlight, annotate and assess the performances of the most altered metabolites between CRC patients (n = 18) and healthy control samples (HC, n = 19) specifically matched for age and gender, two of the most influential confounding factors. On the contrary, due to the difficulty to control for all clinical and demographic traits when sampling small cohorts, the samples from patients in remission (n = 17) were not matched. Because of the consequent risk of bias, the usual null hypothesis significance tests (NHST) could not be applied reliably. Therefore, we compared the R-CRC samples to another specifically matched group of healthy controls (R-HC, n = 17), and used this comparison to indirectly address the difference between patients with colorectal cancer and patients in remission through a measure called effect size (ES) whose methodological aspects were investigated. Results: 24 candidate biomarkers were found significantly altered and able to discriminate the CRC and HC samples efficiently (Receiver Operating Characteristic (ROC) area under the curve (AUC) of 0.86, sensitivity and specificity of 0.72 and 0.78). 10 of those were found to have signals close to healthy levels in the R-CRC samples and were therefore specific to colorectal cancer. In the point-biserial case studied here, r-like (strength of association) and d-like (standardized mean difference) ES were directly convertible and only linear and rank-based ES were different. We therefore used and recommend Hedges' g, Spearman's rho and Kendall's tau, along with an unstandardized ES. The confidence intervals, that quantify the uncertainty of the measure, were well represented through scatterplots and distribution curves. Conclusion: The candidate biomarkers found, along with their specificity, could help for the detection of colorectal cancer, the diagnosis of remission, and for the understanding of its pathophysiology, after proper validation on independent cohorts. The effect size, here applied on a MS global profiling data set, is an ideal complement to NHST and a useful tool to compare and combine distinct cohorts, within a study as well as between studies (meta-analysis). [less ▲]

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See detailExosomal Long Non-Coding RNAs in Lung Diseases
Poulet, Christophe ULiege; NJOCK, Makon-Sébastien ULiege; MOERMANS, Catherine ULiege et al

in International Journal of Molecular Sciences (2020), 21(10), 3580

Within the non-coding genome landscape, long non-coding RNAs (lncRNAs) and their secretion within exosomes are a window that could further explain the regulation, the sustaining, and the spread of lung ... [more ▼]

Within the non-coding genome landscape, long non-coding RNAs (lncRNAs) and their secretion within exosomes are a window that could further explain the regulation, the sustaining, and the spread of lung diseases. We present here a compilation of the current knowledge on lncRNAs commonly found in Chronic Obstructive Pulmonary Disease (COPD), asthma, Idiopathic Pulmonary Fibrosis (IPF), or lung cancers. We built interaction networks describing the mechanisms of action for COPD, asthma, and IPF, as well as private networks for H19, MALAT1, MEG3, FENDRR, CDKN2B-AS1, TUG1, HOTAIR, and GAS5 lncRNAs in lung cancers. We identified five signaling pathways targeted by these eight lncRNAs over the lung diseases mentioned above. These lncRNAs were involved in ten treatment resistances in lung cancers, with HOTAIR being itself described in seven resistances. Besides, five of them were previously described as promising biomarkers for the diagnosis and prognosis of asthma, COPD, and lung cancers. Additionally, we describe the exosomal-based studies on H19, MALAT1, HOTAIR, GAS5, UCA1, lnc-MMP2-2, GAPLINC, TBILA, AGAP2-AS1, and SOX2-OT. This review concludes on the need for additional studies describing the lncRNA mechanisms of action and confirming their potential as biomarkers, as well as their involvement in resistance to treatment, especially in non-cancerous lung diseases. [less ▲]

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See detailIncreased Endoplasmic Reticulum stress specific chaperones characterise CD fibrosis epithelium tissues and participates to in vitro induction of intestinal fibroblasts differentiation
Vieujean, Sophie ULiege; Hu, Shurong; Bequet, Emeline ULiege et al

Poster (2020, March 05)

Background: Intestinal fibrosis is a complication of Crohn’s disease (CD) characterized by myofibroblasts and extracellular matrix accumulation within the submucosa and smooth muscles, leading to bowel ... [more ▼]

Background: Intestinal fibrosis is a complication of Crohn’s disease (CD) characterized by myofibroblasts and extracellular matrix accumulation within the submucosa and smooth muscles, leading to bowel strictures. No medical treatment exists to treat or reverse intestinal fibrosis leading often to surgical resection. The potential role of intestinal epithelium in the fibrotic process remains poorly defined. Methods: We performed a pilot study on ileal fibrostricturing CD surgical samples (n=5), comparing the proteome of surface epithelium isolated by laser capture microdissection in normal and fibrotic zones. Confirmation of the specific protein increases was obtained by immunohistochemistry in colonic and ileal samples of CD (n=44) compared to healthy subjects (n=40), as well as in intestinal epithelial cell line under induced Endoplasmic Reticulum (ER) stress. A model of fibroblast to myofibroblast differentiation induction was also challenged using preconditioned media of intestinal epithelial cells after a pulsed ER stress. Results: Label free proteomics revealed high ER stress in the epithelium surrounding fibrotic bowel wall, involving Anterior gradient protein 2 homolog (AGR2) and 78kDA glucose regulated protein (BiP). Confirmation of both proteins increase was obtained by immunohistochemistry. ER stress induction in intestinal epithelial cells was associated with an intracellular increase of AGR2, BiP and ER stress markers as sXPB1 and CHOP. AGR2 was also detected in the culture medium of these epithelial cells and myofibroblast differentiation was obtained using this culture medium. Conclusions: The increase of ER stress proteins observed in fibrostenosing tissues together with These preliminary evidences of fibroblast to myofibrobast differentiation obtained by paracrine action of intestinal epithelial cell preconditioned to ER stress induction, suggest a role of epithelial ER stress in Crohn’s disease intestinal fibrosis. [less ▲]

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See detailSLC12A2 as a potential histological marker of ulcerative colitis associated colorectal dysplasia
Merli, Angela-Maria ULiege; Vieujean, Sophie ULiege; Massot, Charlotte et al

Conference (2020, March 04)

Introduction: Patients suffering from ulcerative colitis (UC) are at increased risk of developing dysplasia (DAI) and colorectal cancer (CAC). Differentiating DAI from inflammation remains difficult for ... [more ▼]

Introduction: Patients suffering from ulcerative colitis (UC) are at increased risk of developing dysplasia (DAI) and colorectal cancer (CAC). Differentiating DAI from inflammation remains difficult for both endoscopists and anatomopathologists due to macro and microscopic features shared by these lesions. Aim: The aim of our work was to confirm, by histological evaluation, a potential proteomic biomarker discriminating early DAI lesions from chronic inflamed and normal tissues in UC. Methods: We included 15 paired tissues from UC patients (n=5) presenting low-grade DAI. Epithelial cells were isolated by laser capture microdissection and analyzed by label-free proteomics. We selected one protein differentially distributed between DAI, inflamed (I) and normal (N) tissues for confirmation by immunochemistry (IHC). IHC characterization was performed using both the staining intensity score (0 to 4) and the staining pattern: “gradient” (staining intensity increasing from the epithelium lumen to the bottom of the crypts) or “no gradient” (homogenous staining). UC patients with DAI (n=28), dysplastic lesion in non-inflammatory colon (DSp) (n=9), CAC (n=14) and at high risk of CAC (>10 years of UC duration) but free of dysplasia or cancer (n=23) were included. We further studied this potential marker tissue distribution in the mouse model of CAC (AOM/DSS treated mice) to trace its presentation at different evolution stages and assessed low (n=51), high-grade DAI (n=35) and CAC (n=38), as well as relevant paired control tissues. This potential tissue marker was finally evaluated in sporadic precancerous colorectal lesions of UC-free patients with low (n=19) and highgrade (n=16) adenomas and cancerous lesions (CRC): pT1 to pT4 (n=82) and compared to paired normal tissues when available. Results: Proteomics identified 1070 proteins among which 19 showed a differential distribution between DAI and I or N. The sodium chloride co-transporter SLC12A2 was only identified in DAI. SLC12A2 IHC “no gradient” staining pattern was associated to DAI and DSp compared to I or N (with p <0.0001 and 0.0002 respectively). The IHC score was also higher for DAI, DSp and CAC compared to paired I and N (p<0.0001 and 0.0084 respectively). These results were confirmed from low-grade dysplasia to more advanced lesions in the AOM/DSS mice model. The “no gradient” pattern was also significantly associated to low and high-grade adenomas, and CRC of UC-free patients compared to normal control tissues. The sensitivity and specificity of SLC12A2 histological pattern reached 89% and 95% for DAI versusI; 90% and 93% for CAC and/or DAI versus I. In addition, the sensitivity and specificity reached 99% and 87% for all precancerous and cancerous lesions (DAI, DSp, CAC and CRC) versus N and I (including also non-progressing UC patients). Conclusions: A specific histological pattern for SLC12A2 is associated to precancerous and cancerous colorectal lesions, and is able to be discriminate these lesions from inflammation and normal tissue in UC. The continuous upregulation of SLC12A2 in advanced colorectal lesionsin the CAC mice model also suggests a role of this protein in the pathophysiology of inflammation-associated colon neoplasia. [less ▲]

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See detailColorectal Cancer : Biomarkers and Effect Size
Di Giovanni, Nicolas ULiege; Meuwis, Marie-Alice ULiege; Louis, Edouard ULiege et al

Poster (2020, January 22)

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See detailSystematic review and external validation of prediction models based on symptoms and biomarkers for identifying endoscopic activity in Crohn's disease.
Brand, Eelco C.; Elias, Sjoerd G.; Minderhoud, Itta M. et al

in Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2020)

BACKGROUND & AIMS: Endoscopic healing, an important target of treatment for Crohn's Disease (CD), requires ileocolonoscopy, which is costly and burdensome. We investigated whether published non-invasive ... [more ▼]

BACKGROUND & AIMS: Endoscopic healing, an important target of treatment for Crohn's Disease (CD), requires ileocolonoscopy, which is costly and burdensome. We investigated whether published non-invasive models (based on symptoms and biomarkers) to evaluate CD activity have sufficient accuracy to replace ileocolonoscopy. METHODS: We performed a systematic review of published non-invasive diagnostic models to evaluate CD activity that used endoscopic features of activity (endoscopic activity) or healing as the reference standard. We externally validated these models for the outcome endoscopic activity (CD endoscopic index of severity scores of 3 or more) using data from the TAILORIX study (346 ileocolonoscopies in 155 patients) and the Utrecht Activity Index (UAI) study (93 ileocolonoscopies in 82 patients). We calculated area under the receiver operating characteristic curves (AUCROCs) for the models using data from these studies, and compared the performance of these models against measurements of fecal calprotectin (FC) and C-reactive protein (CRP). RESULTS: We screened 5303 articles and identified 27 models (from 21 studies) for our analysis. Seven models could be externally validated; in the TAILORIX dataset, these models identified patients with endoscopic activity with AUROC values ranging from 0.61 (95% CI, 0.51-0.70) to 0.81 (95% CI, 0.76-0.86). In this dataset, the AUROC value for FC concentration was 0.79 (95% CI, 0.74-0.85) and the AUROC value for CRP level was 0.72 (95% CI, 0.66-0.77). The AUROC values for the validation in the UAI-dataset were similar. In the TAILORIX and/or UAI-dataset, 4 of the 7 models, as well as the FC and CRP assays, were able to identify patients with endoscopic activity with positive predictive values of 90% or more. Two of the 7 models (but not the FC or CRP values) identified patients without endoscopic activity with a negative predictive value (NPV) of 90% or more, leading to correct prediction of endoscopic healing in 3.2% to 11.3% of all patients. For example, applying the Herranz-Bachiller model (1 of 7 models) at a NPV of 92.1% and positive predictive value of 91.9% correctly identified 35.7% of all patients in whom ileocolonoscopy could be avoided for expected endoscopic activity or healing but incorrectly identified 3.2% of all patients. Most ileocolonoscopies (66.5% in TAILORIX and 72.6% in the UAI of all ileocolonoscopies) could correctly be avoided based on concentrations of FC of 100 mug/g or less and 250 mug/g or higher. However, using this range of FC concentrations to identify patients that don't require ileocolonoscopy caused 18.7% of all patients in the TAILORIX cohort and 19.8% of all patients in the UAI cohort to incorrectly being predicted to have endoscopic activity or healing.. CONCLUSIONS: In a systematic review and external validation of non-invasive models to identify patients with endoscopic activity of CD, we found only 2 of 7 models evaluated to have NPVs of 90% or more, however, only leading to correct predicted EH in a small proportion of patients. Ileocolonoscopy must therefore be used to evaluate CD mucosal disease activity and healing. [less ▲]

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See detailDe-escalation of immunomodulator and biological therapy in inflammatory bowel disease.
Chapman, Thomas P.; Gomes, Catarina Frias; Louis, Edouard ULiege et al

in Lancet. Gastroenterology and Hepatology (2020), 5(1), 63-79

Treatment strategies for inflammatory bowel disease (IBD) focus on the induction and long-term maintenance of deep remission to avoid complications of active disease and improve long-term outcomes ... [more ▼]

Treatment strategies for inflammatory bowel disease (IBD) focus on the induction and long-term maintenance of deep remission to avoid complications of active disease and improve long-term outcomes. Medical therapies for IBD, notably the increasingly widespread use of biological therapy, are often effective at controlling disease, but these drugs are associated with substantial adverse events, which together with other factors-including increasing treatment costs and patient preferences-leads to concerns regarding indefinite use of medical therapy. Consequently, the need to consider the safety and feasibility of drug de-escalation once IBD remission has been achieved is clear. Here, we review the current evidence surrounding de-escalation of immunomodulator and biological therapy in Crohn's disease and ulcerative colitis. We discuss strategies for de-escalation, including the selection of patients who are appropriate for treatment de-escalation and the use of proactive drug monitoring, and review the evidence on subsequent optimal follow-up. We conclude by proposing an algorithm to guide de-escalation decisions, and highlight future perspectives, including the potential effect of emerging medication and personalised medicine for these diseases. [less ▲]

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See detailUntargeted Serum Metabolic Profiling by Comprehensive Two-Dimensional Gas Chromatography-High-Resolution Time-of-Flight Mass Spectrometry.
Di Giovanni, Nicolas ULiege; MEUWIS, Marie-Alice ULiege; Louis, Edouard ULiege et al

in Journal of Proteome Research (2020), 19

While many laboratories take appropriate care, there are still cases where the performances of untargeted profiling methods suffer from a lack of design, control, and articulation of the various steps ... [more ▼]

While many laboratories take appropriate care, there are still cases where the performances of untargeted profiling methods suffer from a lack of design, control, and articulation of the various steps involved. This is particularly harmful to modern comprehensive analytical instrumentations that otherwise provide an unprecedented coverage of complex matrices. In this work, we present a global analytical workflow based on comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry. It was optimized for sample preparation and chromatographic separation and validated on in-house quality control (QC) and NIST SRM 1950 samples. It also includes a QC procedure, a multiapproach data (pre)processing workflow, and an original bias control procedure. Compounds of interest were identified using mass, retention, and biological information. As a proof of concept, 35 serum samples representing three subgroups of Crohn's disease (with high, low, and quiescent endoscopic activity) were analyzed along with 33 healthy controls. This led to the selection of 33 unique candidate biomarkers able to classify the Crohn's disease and healthy samples with an orthogonal partial least-squares discriminant analysis Q(2) of 0.48 and a receiver-operating-characteristic area under the curve of 0.85 (100% sensitivity and 82% specificity in cross validation). Fifteen of these 33 candidates were reliably annotated (Metabolomics Standards Initiative level 2). [less ▲]

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See detailApproche critique du traitement prolonge par inhibiteurs de la pompe a protons chez les personnes agees.
DELHOUGNE, Nicolas ULiege; Allepaerts, Sophie ULiege; GAST, Pierrette ULiege et al

in Revue medicale de Liege (2020), 75(1), 10-16

Proton pump inhibitors (PPI) are drugs frequently used for gastric acid-induced conditions. Their use is constantly increasing and due to the apparent absence of side-effects, the treatment is not ... [more ▼]

Proton pump inhibitors (PPI) are drugs frequently used for gastric acid-induced conditions. Their use is constantly increasing and due to the apparent absence of side-effects, the treatment is not reassessed, even for the elderly. However, there are many cases of misprescribing while concerns about some side-effects are rising. Old people are weakened by their particular homeostasis and their associated medical conditions. Therefore, it seems useful to particularly insist on side-effects of the PPI, their indications and the ways of withdrawal, first of all for the elderly. [less ▲]

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See detailPregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti-TNF or conventional therapy: results of the European CONCEIVE study.
Moens, Annick; van der Woude, C. Janneke; Julsgaard, Mette et al

in Alimentary pharmacology & therapeutics (2020), 51(1), 129-138

BACKGROUND: Women with inflammatory bowel diseases (IBD) often receive biologicals during pregnancy to maintain disease remission. Data on outcome of vedolizumab-exposed pregnancies (VDZE) are sparse ... [more ▼]

BACKGROUND: Women with inflammatory bowel diseases (IBD) often receive biologicals during pregnancy to maintain disease remission. Data on outcome of vedolizumab-exposed pregnancies (VDZE) are sparse. AIMS: To assess pregnancy and child outcomes of VDZE pregnancies and to compare these results to anti-TNF exposed (TNFE) or both immunomodulatory and biologic unexposed (CON IBD) pregnancies. METHODS: A retrospective multicentre case-control observational study was performed. RESULTS: VDZE group included 79 pregnancies in 73 IBD women. The TNFE and CON IBD group included 186 pregnancies (162 live births) in 164 IBD women and 184 pregnancies (163 live births) in 155 IBD women, respectively. At conception, cases more often had active disease ([VDZE: 36% vs TNFE: 17%, P = .002] and [VDZE: 36% vs CON IBD: 24%, P = .063]). No significant difference in miscarriage rates were found between groups (VDZE and TNFE: 16% vs 13%, P = .567; VDZE and CON IBD: 16% vs 10%, P = .216). In live-born infants, median gestational age and birthweight were similar between groups. Median Apgar score at birth was numerically equal. Prematurity was similar in the VDZE group compared to the control groups, even when correcting for disease activity during pregnancy. The frequency of congenital anomalies was comparable between groups as were the percentages of breastfed babies. During the first year of life, no malignancies were reported and infants' infection risk did not significantly differ between groups. CONCLUSION: No new safety signal was detected in VDZE pregnancies although larger, prospective studies are required for confirmation. [less ▲]

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See detailControl and Interpretation of Untargeted Metabolomics Data
Di Giovanni, Nicolas ULiege; Meuwis, Marie-Alice ULiege; Louis, Edouard ULiege et al

Scientific conference (2019, July 08)

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See detailColorectal Cancer : Biomarkers and Effect Size
Di Giovanni, Nicolas ULiege; Meuwis, Marie-Alice ULiege; Louis, Edouard ULiege et al

Poster (2019, June 23)

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See detailColorectal cancer research with GC×GC-(HR)TOFMS
Di Giovanni, Nicolas ULiege; MEUWIS, Marie-Alice ULiege; Louis, Edouard ULiege et al

Conference (2019, June 12)

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See detailColorectal Cancer : Biomarkers and Effect Size
Di Giovanni, Nicolas ULiege; Meuwis, Marie-Alice ULiege; Louis, Edouard ULiege et al

Poster (2019, May 21)

Colorectal cancer kills more than 700.000 persons each year worldwide. Nevertheless, its diagnosis is still largely based on invasive tissue sampling and gaps remain in the understanding of its ... [more ▼]

Colorectal cancer kills more than 700.000 persons each year worldwide. Nevertheless, its diagnosis is still largely based on invasive tissue sampling and gaps remain in the understanding of its pathogenesis, with complex combinations between lifestyle, genetics, epigenetics, chronic inflammation (IBD) and microbiota. We analyzed serum samples from patients affected by colorectal cancer (CRC, n = 18) and by colorectal cancer in remission (R-CRC, n = 17), and samples from healthy patients matched for biases (HC, n = 19 and R-HC, n = 17). The aim was to find candidate biomarkers able to diagnose the active state of the disease as well as to compare the concentration levels of the molecules of interest with the remission state to better understand the biolocal processes beneath the observed clinical and metabolic symptoms. To do so, an optimized and validated (NIST SRM 1950) comprehensive GC×GC-(HR)TOFMS method we developed was used. It includes an in-house QC system, data processing based on multiple statistical techniques and identification using full mass spectrum, linear retention indices and accurate mass provided by state-of-the-art high-resolution (HR) time-of-flight mass spectrometry. Because the experimental design prevented a direct comparison between the active and remission samples, which were not directly matched for biases, we used a measure called effect size that has the advantage to not only focus on statistical significance but on effect (here signal variation) magnitude. We will discuss the interest and application of effect size in metabolomics and we will present the highlighted candidate biomarkers in terms of discrimination potential. [less ▲]

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See detailGanglionic tuberculosis in a Crohn’s disease patient treated by infliximab despite anti-tuberculosis chemoprophylaxis
VIEUJEAN, Sophie ULiege; BURY, Thierry ULiege; GASPARD, Laura ULiege et al

Conference (2019, February)

Infliximab is an IgG1κ monoclonal antibody against tumor necrosis factor-α (anti-TNFα) who have significantly improved the management of patients with Inflammatory Bowel Diseases (IBD), but with an ... [more ▼]

Infliximab is an IgG1κ monoclonal antibody against tumor necrosis factor-α (anti-TNFα) who have significantly improved the management of patients with Inflammatory Bowel Diseases (IBD), but with an increased risk of opportunistic infection, especially tuberculosis (TB). We report a case of a 54 years-old man with an ileal Crohn’s disease (CD) diagnosed in July 2014 (Montreal classification at diagnosed: A2L1B1p-). Patient was an active smoker and was treated by budesonide for several flares. Two years after diagnosis, since he has been hospitalised for subocclusion treated with methylprednisolone, combination therapy by mercaptopurine and anti-TNFα was discussed for steroid dependence. Patient was screened for tuberculosis (TB). A latent tuberculosis (LTB) was highlighted based on a positive interferon-gamma release assay (QuantiFERON TB) without clinical, microbiological and radiological evidence of active disease. A nine-month course of isoniazid (INH) 300 mg/day was started 4 weeks before the combination therapy with thiopurine/infliximab at the recommended doses. This treatment allowed a clinical remission and thiopurine could be stopped. Six months after completing INH for LTB and 1 month after cessation of thiopurine, patient was admitted in our emergency department for fever, dyspnoea and cough. Chest tomography showed large lymphadenopathies in the right pulmonary hilum and in the mediastinum. A fibroscopy with a bronchoalveolar lavage (with looking for bacillus of Koch) and an endobronchial ultrasound with biopsies were performed, both negative. Finally, a diagnosis of ganglionic tuberculosis was settled by a positive microscopic exam (auramine coloration) on an excised cervical lymphadenopathy. No resistance to usual anti-tuberculosis treatment was highlighted. Infliximab was immediately discontinued and anti-tuberculosis 4-drug regimen was initiated. Patient received Vedolizumab as IBD treatment 1 month later and he did not present any recurrence of TB infection or new flare of Crohn's disease up until now. This case report emphasizes that chemoprophylaxis for LTB does not completely protect against reactivation of TB in IBD patients treated by anti-TNF. It could be useful to study risk factors for reactivation of LTB in this treated by biologics population (monotherapy or combination therapy) to establish a case-by-case monitoring. [less ▲]

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See detailAlcool et complications pancréatiques
LOLY, Jean-Philippe ULiege; MEURISSE, Nicolas ULiege; GAST, Pierrette ULiege et al

in Revue Médicale de Liège (2019), 74(5-6), 342-348

Alcohol consumption is the main cause of development of chronic pancreatitis and the second etiology of acute pancreatitis. The mortality of acute pancreatitis depends on its necrotic haemorrhagic ... [more ▼]

Alcohol consumption is the main cause of development of chronic pancreatitis and the second etiology of acute pancreatitis. The mortality of acute pancreatitis depends on its necrotic haemorrhagic character and the initial inflammatory response, while pain, malnutrition and diabetes are the main issues in the management of chronic pancreatitis. As medical and endoscopic techniques progress, surgical indications have become increasingly rare but remain indispensable for some patients. The multidisciplinary approach of these patients is the key to the success of care.La consommation d’alcool est la cause principale de développement d’une pancréatite chronique et la seconde étiologie de la pancréatite aiguë. La mortalité de la pancréatite aiguë dépend de son caractère nécrotico-hémorragique et de la réponse inflammatoire initiale tandis que les complications de type douleur, dénutrition et diabète sont les principaux enjeux de la prise en charge de la pancréatite chronique. Au fur et à mesure de l’avancée des techniques médicales et endoscopiques, les indications chirurgicales sont devenues de plus en plus rares, mais restent indispensables pour certains patients. L’approche pluridisciplinaire de ces patients est la clé du succès de la prise en charge. [less ▲]

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See detailOn-site comparison of an enzymatic detergent and a non-enzymatic detergent-disinfectant for routine manual cleaning of flexible endoscopes.
Gonzalez, Jonathan Alfageme; Vanzieleghem, Thomas; Dumazy, Axelle ULiege et al

in Endoscopy International Open (2019), 7(4), 412-420

Background and study aims Flexible endoscopes are potential vectors of pathogen transmission to patients that are subjected to cleaning and high-level disinfection after each procedure. Efficient manual ... [more ▼]

Background and study aims Flexible endoscopes are potential vectors of pathogen transmission to patients that are subjected to cleaning and high-level disinfection after each procedure. Efficient manual cleaning is a prerequisite for effective high-level disinfection. The goal of this study was to demonstrate the impact of the cleaning chemistry in the outcome of the manual cleaning of endoscopes. Materials and methods Twelve endoscopes were included in this study: four colonoscopes, four gastroscopes, two duodenoscopes and two bronchoscopes. This study was designed with two phases; in each of them, the manual cleaning procedure remained identical, but a different detergent was used: a non-enzymatic detergent-disinfectant (NEDD) and an enzymatic detergent (ED). Biopsy and suction channels of endoscopes were sampled using 10 mL of physiological saline at two points: before and after manual cleaning, and adenosine triphosphate (ATP) was measured on each sample. In total, 208 procedures were analyzed for the NEDD phase and 253 for the ED phase. Results For each endoscope type, cleaning endoscopes with ED resulted in larger median decrease in ATP than with NEDD: respectively 99.43 % and 95.95 % for bronchoscopes ( P = 0.0007), 99.28 % and 96.93 % for colonoscopes ( P < 0.0001) and 98.36 % and 95.36 % for gastroscopes ( P < 0.0001). In addition, acceptability rates of endoscopes based on defined post-manual cleaning ATP thresholds (200, 150, 100 or 50 relative light units) for all endoscope types were significantly higher with ED compared to NEDD. Conclusions With all other parameters of manual cleaning remaining unchanged, the enzymatic chemistry of ED provided more consistent and improved cleaning of endoscopes compared to NEDD. Therefore, choice of the detergent for endoscope cleaning has an impact on the outcome of this process. [less ▲]

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See detailRisk of Development of More-advanced Lesions in Patients With Inflammatory Bowel Diseases and Dysplasia.
Cremer, Anneline; Demetter, Pieter; De Vos, Martine et al

in Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2019)

BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBD) have increased risks of dysplasia and colitis-associated cancer (CAC). We evaluated the risk of development of high-grade dysplasia (HGD ... [more ▼]

BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBD) have increased risks of dysplasia and colitis-associated cancer (CAC). We evaluated the risk of development of high-grade dysplasia (HGD) or CAC after diagnosis of dysplasia using data from a national cohort of patients with IBD. METHODS: We performed a multicenter retrospective analysis of data collected from 7 tertiary referral regional or academic centers in Belgium. In searches of IBD pathology databases, we identified 813 lesions (616 low-grade dysplasias [LGDs], 64 high-grade dysplasias [HGDs], and 133 CACs) in 410 patients with IBD: 299 had dysplasia (73%) and 111 had CAC (27%). The primary aim was to determine the risk of more-advanced lesions after diagnosis of LGD or HGD. RESULTS: Of the 287 patients with LGD, 21 (7%) developed more-advanced lesions (HGD or CAC) after a median time period of 86 months (interquartile range, 34-214). Of the 28 patients with HGD, 4 (14%) developed CAC after a median time period of 180 months (interquartile range, 23-444). The overall cumulative incidence of CAC at 10 years after an initial diagnosis of HGD was 24.3% and after an initial diagnosis of LGD was 8.5% (P < .05). Metachronous lesions, non-polypoid lesions, and colonic stricture were associated with risk of occurrence of more-advanced lesions after LGD (P < .05). Of the 630 dysplastic lesions identified during endoscopy, 545 (86%) were removed during the same procedure or during a follow-up endoscopy or by surgery. Of 111 patients with CAC, 95 (86%) did not have prior detection of dysplasia and 64 of these 95 patients (67%) developed CAC outside of the screening or surveillance period recommended by the European Crohn's and Colitis Organisation. CONCLUSIONS: In an analysis of pathology data from 7 medical centers in Belgium, we found a low rate of detection of more-advanced lesions following detection of LGD or HGD-taking into account that most of the lesions were removed. Main risk factors for development of more-advanced lesions after LGD were metachronous lesions, non-polypoid lesions, and colon strictures. [less ▲]

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