Titel Deelnemers "Korte inhoud" "Posterior compartment prolapse and perineal descent" "Sylvie Van den Broeck, Sara Nullens, Yves Jacquemyn, Heiko De Schepper, Alexandra Vermandel, Niels Komen" "Objective: The aim of our study is to systematically review the literature about available devices facilitating perineal support during defecation in patients with obstructive defecation syndrome (ODS) and posterior pelvic organ prolapse (POP). Methods: We searched for the terms ""defecat/ion or ODS"" and"" pessar/ies or device/aid/tool/perineal/perianal/prolapse and support"" in MEDLINE, PubMed and Web of Science. Data abstraction was performed according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analysis) guidelines. A two-stage inclusion was performed, selecting first on title and abstract and secondly the full text. For variables with sufficient data, a meta-analysis was performed using a random-effects model. Other variables were descriptively reported. Results: Ten studies out of 1332 were included for systematic review. The devices could be categorized into three groups: pessaries (n = 8), vaginal stent (n = 1) and external support device (n = 1). Methodology and data reporting is heterogeneous. Meta-analysis could be performed for the Colorectal-Anal Distress Inventory (CRADI-8) and Impact Questionnaire (CRAI-Q-7) in three pessary studies which showed a significant mean change. Significant improvement of stool evacuation was seen in two other pessary studies. The vaginal stent significantly decreases ODS. Subjective perception of constipation improved significantly using the posterior perineal support device. Conclusion: All reviewed devices seem to improve ODS in patients with POP. There are no data on their efficacy with regard to perineal descent-associated ODS. There is a lack of comparative studies between devices. Studies are difficult to compare due to different inclusion criteria and evaluation tools." "Secondary anal fissures" "H. Ruymbeke, J. Geldof, D. De Looze, M.A. Denis, Heiko De Schepper, Pieter Dewint, I. Gijsen, M. Surmont, J. Wyndaele, P. Roelandt" "An anal fissure is a painful tear of the sensitive anoderm, distally from the dentate line. It is a prevalent disorder and impairs quality of life dramatically. Typical or primary fissures are associated with constipation and mostly located at the posterior midline. About 1% of fissures are atypical in appearance and are generally secondary in nature. These secondary fissures should arouse attention and require further exploration for underlying conditions, such as Crohn's disease, malignancy, trauma or venereal infections. The aim of this manuscript is to provide a comprehensive review on the clinical aspects, evaluation and treatment of secondary anal fissures. (Acta gastroenterol. belg., 2023, 86, 58-67)." "IL-22-activated MUC13 impacts on colonic barrier function through JAK1/STAT3, SNAI1/ZEB1 and ROCK2/MAPK signaling" "Tom Breugelmans, Wout Arras, Baptiste Oosterlinck, Aranzazu Jauregui, Michaël Somers, Bart Cuypers, Kris Laukens, Joris De Man, Heiko De Schepper, Benedicte De Winter, Annemieke Smet" "Overexpression of the transmembrane mucin MUC13, as seen in inflammatory bowel diseases (IBD), could potentially impact barrier function. This study aimed to explore how inflammation-induced MUC13 disrupts epithelial barrier integrity by affecting junctional protein expression in IBD, thereby also considering the involvement of MUC1. RNA sequencing and permeability assays were performed using LS513 cells transfected with MUC1 and MUC13 siRNA and subsequently stimulated with IL-22. In vivo intestinal permeability and MUC13-related signaling pathways affecting barrier function were investigated in acute and chronic DSS-induced colitis wildtype and Muc13−/− mice. Finally, the expression of MUC13, its regulators and other barrier mediators were studied in IBD and control patients. Mucin knockdown in intestinal epithelial cells affected gene expression of several barrier mediators in the presence/absence of inflammation. IL-22-induced MUC13 expression impacted barrier function by modulating the JAK1/STAT3, SNAI1/ZEB1 and ROCK2/MAPK signaling pathways, with a cooperating role for MUC1. In response to DSS, MUC13 was protective during the acute phase whereas it caused more harm upon chronic colitis. The pathways accounting for the MUC13-mediated barrier dysfunction were also altered upon inflammation in IBD patients. These novel findings indicate an active role for aberrant MUC13 signaling inducing intestinal barrier dysfunction upon inflammation with MUC1 as collaborating partner." "Mucin-microbiome signatures shape the tumor microenvironment in gastric cancer" "Baptiste Oosterlinck, Hannah Ceuleers, Wout Arras, Joris De Man, Karen Geboes, Heiko De Schepper, Marc Peeters, Sarah Lebeer, Jurgita Skieceviciene, Georgina L. Hold, Juozas Kupcinskas, Alexander Link, Benedicte De Winter, Annemieke Smet" "Background and aims We aimed to identify mucin-microbiome signatures shaping the tumor microenvironment in gastric adenocarcinomas and clinical outcomes. Methods We performed high-throughput profiling of the mucin phenotypes present in 108 gastric adenocarcinomas and 20 functional dyspepsia cases using validated mucin-based RT-qPCRs with subsequent immunohistochemistry validation and correlated the data with clinical outcome parameters. The gastric microbiota was assessed by 16S rRNA gene sequencing, taxonomy, and community composition determined, microbial networks analyzed, and the metagenome inferred in association with mucin phenotypes and expression. Results Gastric adenocarcinomas with an intestinal mucin environment or high-level MUC13 expression are associated with poor survival. On the contrary, gastric MUC5AC or MUC6 abundance was associated with a more favorable outcome. The oral taxa Neisseria, Prevotella, and Veillonella had centralities in tumors with intestinal and mixed phenotypes and were associated with MUC13 overexpression, highlighting their role as potential drivers in MUC13 signaling in GC. Furthermore, dense bacterial networks were observed in intestinal and mixed mucin phenotype tumors whereas the lowest community complexity was shown in null mucin phenotype tumors due to higher Helicobacter abundance resulting in a more decreased diversity. Enrichment of oral or intestinal microbes was mucin phenotype dependent. More specifically, intestinal mucin phenotype tumors favored the establishment of pro-inflammatory oral taxa forming strong co-occurrence networks. Conclusions Our results emphasize key roles for mucins in gastric cancer prognosis and shaping microbial networks in the tumor microenvironment. Specifically, the enriched oral taxa associated with aberrant MUC13 expression can be potential biomarkers in predicting disease outcomes." "Prevalence, risk factors and diagnostic accuracy of non-invasive tests for NAFLD in people with type 1 diabetes" "Jonathan Mertens, Jonas Weyler, Eveline Dirinck, Luisa Vonghia, Wilhelmus Kwanten, Laura Mortelmans, Cédric Peleman, Shivani Chotkoe, Maarten Spinhoven, Floris Vanhevel, Luc Van Gaal, Benedicte De Winter, Christophe De Block, Sven Francque" "Background & Aims The epidemiology of non-alcoholic fatty liver disease (NAFLD) in people with type 1 diabetes (T1D) is not yet elucidated. This study aimed to assess the diagnostic accuracy of non-invasive tests for NAFLD, to investigate the prevalence and severity of NAFLD, and to search for factors contributing to NAFLD in people with T1D. Methods In this prospective cohort study, we consecutively screened 530 adults with T1D from a tertiary care hospital, using ultrasound (US), vibration-controlled transient elastography equipped with liver stiffness measurement (LSM) and controlled attenuation parameter, and the fatty liver index. Magnetic resonance spectroscopy (MRS) was performed in a representative subgroup of 132 individuals to validate the diagnostic accuracy of the non-invasive tests. Results Based on MRS as reference standard, US identified individuals with NAFLD with an AUROC of 0.98 (95% CI 0.95–1.00, sensitivity: 1.00, specificity: 0.96). The controlled attenuation parameter was also accurate with an AUROC of 0.85 (95% CI 0.77–0.93). Youden cut-off was ≥270 dB/m (sensitivity: 0.90, specificity: 0.74). The fatty liver index yielded a similar AUROC of 0.83 (95% CI 0.74–0.91), but the conventional cut-off used to rule in (≥60) had low sensitivity and specificity (0.62, 0.78). The prevalence of NAFLD in the overall cohort was 16.2% based on US. Metabolic syndrome was associated with NAFLD (OR: 2.35 [1.08–5.12], p = 0.031). The overall prevalence of LSM ≥8.0 kPa indicating significant fibrosis was 3.8%, but reached 13.2% in people with NAFLD. Conclusions NAFLD prevalence in individuals with T1D is 16.2%, with approximately one in 10 featuring elevated LSM. US-based screening could be considered in people with T1D and metabolic syndrome. Impact and Implications We aimed to report on the prevalence, disease severity, and risk factors of NAFLD in type 1 diabetes (T1D), while also tackling which non-invasive test for NAFLD is the most accurate. We found that ultrasound is the best test to diagnose NAFLD. NAFLD prevalence is 16.2%, and is associated with metabolic syndrome and BMI. Elevated liver stiffness indicating fibrosis is overall not prevalent in people with T1D (3.8%), but it reaches 13.2% in those with T1D and NAFLD." "Pathophysiological mechanisms in irritable bowel syndrome" "Kathleen Van Malderen" "Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder affecting 4-11% of the population. While we know its pathophysiology to be multifactorial, a lot of questions on the exact mechanisms remain unanswered. In this thesis, we investigated some of these pathophysiological mechanisms, more specifically we looked into the potential of cellular and volatile biomarkers. First, we started the thesis by evaluating the epidemiological characteristics of a Dutch speaking population visiting a patient-centred informative website. Red flag symptoms and comorbid psychological disorders were prevalent validating the importance of a thorough characterisation of IBS patients both in clinical practice and research. Despite treatment patients frequently experienced moderate to severe symptoms with an important impact on their quality of life indicating the need of more targeted treatment options. Perhaps one of the most important messages of this study is the urgent need for high-quality, scientifically substantiated information and education for both patients and health care professionals. Second, we validated the use of mast cells (MCs) cultured from peripheral blood progenitors from patients and healthy controls (HC) to investigate the potential of these cell cultures as cellular biomarkers. We compared the immunophenotypic characteristics and functionality of naïve MCs from IBS patients and HC and did not find any basal significant differences. Next, we developed an IBS/gut-like environment based on colonic supernatant in which the MCs can be incubated. While the use of the IBS/gut-like environment has a lot of research potential, further optimisation and validation is needed. At the moment, the colonic supernatant is still a black box containing a variety of compounds with an unknown effect on MCs. A characterisation of the supernatant and identification of compounds of interest is needed. Next, the composition of the supernatant should be optimised to reduce cell toxicity. Third, we validated the potential of volatile organic compounds (VOCs) in IBS. We demonstrated the feasibility of ion mobility spectrometry as a cheaper and easily accessible alternative to GC-MS. With the help of VOC models, we could accurately differentiate IBS patients from healthy controls. Furthermore, we could differentiate IBS patients from each other, and from healthy controls, with the help of VOC models based on the dominant stool pattern. We were also able to differentiate IBS patients from each other with VOC models based on alternative clinical characteristics like psychological comorbidities, microbiota-influencing therapies, and symptom scores." "Aberrant mucin expression profiles associate with pediatric inflammatory bowel disease presentation and activity" "Tom Breugelmans, Wout Arras, Lauren-Emma Boen, Eliah Borms, Lisa Kamperdijk, Joris De Man, Els Van de Vijver, Benedicte De Winter, Nicolette Moes, Annemieke Smet" "Background: Intestinal mucosal healing is nowadays preferred as the therapeutic endpoint in inflammatory bowel disease (IBD), but objective measurements at the molecular level are lacking. Because dysregulated mucin expression is suggested to be involved in mucosal barrier dysfunction in IBD, we investigated mucin expression in association with barrier mediators and clinical characteristics in colonic tissue of a pediatric IBD population. Methods: In this cross-sectional monocentric study, we quantified messenger RNA (mRNA) expression of mucins, intercellular junctions, and cell polarity complexes in inflamed and noninflamed colonic biopsies from pediatric IBD (n = 29) and non-IBD (n = 15) patients. We then validated mucin expression at protein level and correlated mucin mRNA expression with expression of barrier mediators and clinical data. Results: The expression of MUC1, MUC3A, MUC4, and MUC13 was increased in the inflamed colon of pediatric IBD patients compared with the noninflamed colon of non-IBD control subjects. Especially MUC13 mRNA expression associated with the expression of barrier mediators, including CDH1, OCLN, and TJP2. MUC1 and MUC3B mRNA expression in combination with calprotectin levels most accurately discriminated IBD patients from non-IBD control subjects (90.6% area under the receiver-operating characteristic curve [AUC ROC], 92.0% sensitivity, 73.7% specificity), whereas aberrant mRNA expression of MUC1, MUC3A, MUC4, and MUC13 was distinctive for ulcerative colitis and of MUC3B for Crohn's disease. Furthermore, expression of MUC3A, MUC3B, and MUC4 correlated with clinical disease activity (ie, Pediatric Ulcerative Colitis Activity Index and Pediatric Crohn's Disease Activity Index), and of MUC1, MUC2, MUC4, and MUC13 with endoscopic colitis severity in ulcerative colitis patients. Conclusions: Colonic mucin expression is disturbed in pediatric IBD patients and associates with disease activity and presentation, suggesting its use as molecular marker to aid in disease diagnosis and management." "Urinary epidermal growth factor reflects vascular health in boys with either obesity or type 1 diabetes" "Kristien Ledeganck, Annelies Van Eyck, Eline Vermeiren, Benedicte De Winter, Stijn Verhulst, Kim Van Hoorenbeeck, Annick France, Hilde Dotremont, Marieke den Brinker" "An increased blood pressure is a known comorbidity of both type 1 diabetes (T1DM) and obesity in children. Increasing evidence suggests a subtle interplay between epidermal growth factor (EGF) and renin along the juxtaglomerular system, regulating the impact of blood pressure on kidney health and the cardiovascular system. In this study, we investigated the relation between urinary EGF, serum renin and blood pressure in children with obesity or T1DM. 147 non-obese children with T1DM and 126 children with obesity, were included. Blood pressure was measured and mean arterial pressure (MAP) and the pulse pressure (PP) were calculated. Serum renin and urinary EGF levels were determined with a commercial ELISA kit. Partial Spearman rank correlation coefficients and multiple linear regression models were used to study the association between renin, the urinary EGF/urinary creatinine ratio and blood pressure parameters. The urinary EGF/urinary creatinine ratio is correlated with the SBP and the MAP in boys with obesity as well as in boys with T1DM. Multiple regression analysis showed that sex and pulse pressure in male subjects were found to be independently associated with renin. Sex, the presence of diabetes, age, the glomerular filtration rate and both pulse pressure and mean arterial pressure in male subjects were independently associated with urinary EGF/urinary creatinine. In conclusion, in boys with either obesity or diabetes, pulse pressure and mean arterial pressure are negatively associated with the functional integrity of the nephron, which is reflected by a decreased expression of urinary EGF." "Zonated quantification of immunohistochemistry in normal and steatotic livers" "Cédric Peleman, Winnok De Vos, Isabel Pintelon, Ann Driessen, Annelies Van Eyck, Christophe Van Steenkiste, Luisa Vonghia, Joris De Man, Benedicte De Winter, Tom Vanden Berghe, Sven Francque, Wilhelmus Kwanten" "Immunohistochemical stains (IHC) reveal differences between liver lobule zones in health and disease, including nonalcoholic fatty liver disease (NAFLD). However, such differences are difficult to accurately quantify. In NAFLD, the presence of lipid vacuoles from macrovesicular steatosis further hampers interpretation by pathologists. To resolve this, we applied a zonal image analysis method to measure the distribution of hypoxia markers in the liver lobule of steatotic livers.The hypoxia marker pimonidazole was assessed with IHC in the livers of male C57BL/6 J mice on standard diet or choline-deficient L-amino acid-defined high-fat diet mimicking NAFLD. Another hypoxia marker, carbonic anhydrase IX, was evaluated by IHC in human liver tissue. Liver lobules were reconstructed in whole slide images, and staining positivity was quantified in different zones in hundreds of liver lobules. This method was able to quantify the physiological oxygen gradient along hepatic sinusoids in normal livers and panlobular spread of the hypoxia in NAFLD and to overcome the pronounced impact of macrovesicular steatosis on IHC. In a proof-of-concept study with an assessment of the parenchyma between centrilobular veins in human liver biopsies, carbonic anhydrase IX could be quantified correctly as well.The method of zonated quantification of IHC objectively quantifies the difference in zonal distribution of hypoxia markers (used as an example) between normal and NAFLD livers both in whole liver as well as in liver biopsy specimens. It constitutes a tool for liver pathologists to support visual interpretation and estimate the impact of steatosis on IHC results." "Epidemiological characteristics of a population visiting a patient-centered informative website about irritable bowel syndrome" "Kathleen Van Malderen, Joris De Man, Benedicte De Winter, Heiko De Schepper" "Background and aims: Irritable bowel syndrome (IBS) is a chronic disorder characterized by abdominal pain and an altered bowel habit. The aim of this study was to evaluate the characteristics of a population visiting a patient-centered informative website about IBS.Methods: Five digital surveys were used to assess the Rome IV criteria, red flag symptoms, healthcare use, psychological comorbidities, quality of life, symptom severity, diet, physical activity. Patients were divided into a Rome positive and negative population with the Rome positive population being further subtyped based on dominant stool pattern.Results: Red flag symptoms (42%) and comorbid psychological disorders (65% anxiety and 39% depression) were common. Despite consulting health care professionals and therapy, most patients (96%) still experienced moderate to severe symptoms with an average impact on quality of life. 73% performed regular physical exercise and 25% of the Rome positive population followed the FODMAP diet. Almost all participants consulted a health care professional at one point in time and used some form of therapy. 54% of the patients believed there is generally sufficient information available and 57% thinks that their physician takes IBS seriously. However, only 41% thinks that their physician has sufficient knowledge about IBS.Conclusions: This study underlines the importance of a thorough characterization of IBS patients. Furthermore, patients expressed an urgent need for high quality information and education for both health care professionals and patients."