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1. Ferroptosis is a targetable detrimental factor in metabolic dysfunction-associated steatotic liver disease

Author

Peleman, Cédric, Hellemans, Stig, Veeckmans, Geraldine, Arras, Wout, Zheng, Hao, Koeken, Ine, Van San, Emily, Hassannia, Behrouz, Walravens, Magali, Kayirangwa, Edissa, Beyene, Nateneal Tamerat, Van Herck, Mikhaïl Alfons, De Vos, Winnok Harald, Pintelon, Isabel, van Nassauw, Luc, Oosterlinck, Baptiste, Smet, Annemieke, Vits, Lieve, Dirinck, Eveline, Verrijken, An, De Man, Joris, Van Eyck, Annelies, Kwanten, Wilhelmus Josephus, Vonghia, Luisa, Driessen, Ann, Augustyns, Koen, Toyokuni, Shinya, De Winter, Benedicte, Van Steenkiste, Christophe, Francque, Sven, and Vanden Berghe, Tom

Published
2024
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2. Author Correction: Organ-specific genome diversity of replication-competent SARS-CoV-2

Author

Van Cleemput, Jolien, van Snippenberg, Willem, Lambrechts, Laurens, Dendooven, Amélie, D’Onofrio, Valentino, Couck, Liesbeth, Trypsteen, Wim, Vanrusselt, Jan, Theuns, Sebastiaan, Vereecke, Nick, van den Bosch, Thierry P. P., Lammens, Martin, Driessen, Ann, Achten, Ruth, Bracke, Ken R., Van den Broeck, Wim, Von der Thüsen, Jan, Nauwynck, Hans, Van Dorpe, Jo, Gerlo, Sarah, Maes, Piet, Cox, Janneke, and Vandekerckhove, Linos

Published
2022
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3. Studying the clinical, radiological, histological, microbiological, and immunological evolution during the different COVID-19 disease stages using minimal invasive autopsy

Author

D’Onofrio, Valentino, Keulen, Lotte, Vandendriessche, Annelore, Dubois, Jasperina, Cartuyvels, Reinoud, Vanden Abeele, Marie-Elena, Fraussen, Judith, Vandormael, Patrick, Somers, Veerle, Achten, Ruth, Dendooven, Amélie, Driessen, Ann, Augsburg, Lukasz, Hellings, Niels, Lammens, Martin, Vanrusselt, Jan, and Cox, Janneke

Published
2022
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5. Organ-specific genome diversity of replication-competent SARS-CoV-2

Author

Van Cleemput, Jolien, van Snippenberg, Willem, Lambrechts, Laurens, Dendooven, Amélie, D’Onofrio, Valentino, Couck, Liesbeth, Trypsteen, Wim, Vanrusselt, Jan, Theuns, Sebastiaan, Vereecke, Nick, van den Bosch, Thierry P. P., Lammens, Martin, Driessen, Ann, Achten, Ruth, Bracke, Ken R., Van den Broeck, Wim, Von der Thüsen, Jan, Nauwynck, Hans, Van Dorpe, Jo, Gerlo, Sarah, Maes, Piet, Cox, Janneke, and Vandekerckhove, Linos

Published
2021
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7. Belgian consensus for Helicobacter pylori management 2023

Author

Garces-Duran, R., Kindt, S., Kotilea, K., Francois, S., Rasschaert, G., Smet, Annemieke, Hauser, B., Driessen, Ann, Nkuize, M., Burette, A., Lamy, V., Bontems, P., Louis, H., Ntounda, R., Deyi, V.Y. Miendje, Mana, F., Clinical sciences, Internal Medicine, Gastroenterology, Growth and Development, Pediatrics, Faculty of Medicine and Pharmacy, and Belgian Helicobacter Pylori

Subjects
Helicobacter Infections/drug therapy, Anti-Bacterial Agents/therapeutic use, Consensus, Helicobacter pylori, Belgium, Humans, Human medicine
Abstract

Helicobacter pylori (H. pylori) infection causes chronic gastritis, peptic ulcers and gastric cancer. Although H. pylori prevalence is decreasing worldwide, regional variations exist in Europe, with the lowest infection prevalence in Northern Europe, and the highest in Eastern and Southern Europe (1). Changes in the treatment recommendations and the increasing available evidence have justified the implementation of new recommendations since last Belgian consensus in 1998 (2). Several non-H. pylori Helicobacter species (NH.PYLORI-H), colonizing the stomach of domestic animals, also have the ability to cause gastric disease in humans, although to a lesser extent. These zoonotic NH. PYLORIH are not the subject of the current recommendations.

Published
2023
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8. Machine learning algorithm improves the detection of NASH (NAS-based) and at-risk NASH: A development and validation study

Author

Jenny, Lee, Max, Westphal, Yasaman, Vali, Jerome, Boursier, Salvatorre, Petta, Rachel, Ostroff, Leigh, Alexander, Yu, Chen, Celine, Fournier, Andreas, Geier, Sven, Francque, Kristy, Wonder, Dina, Tiniako, Pierre, Bedossa, Mike, Allison, Georgios, Papatheodoridi, Helena, Cortez-Pinto, Raluca, Pai, Jean-Francois, Dufour, Diana Julie, Leeming, Stephen, Harrison, Jeremy, Cobbold, Adriaan G, Holleboom, Hannele, Yki-Järvinen, Javier, Crespo, Mattias, Ekstedt, Guruprasad P, Aithal, Elisabetta, Bugianesi, Manuel, Romero-Gomez, Richard, Torstenson, Morten, Karsdal, Carla, Yuni, Jörn M, Schattenberg, Detlef, Schuppan, Vlad, Ratziu, Clifford, Bra, Kevin, Duffin, Koos, Zwinderman, Michael, Pavlide, Quentin M, Anstee, Patrick M, Bossuyt, Anstee, Quentin M., Daly, Ann K., Govaere, Olivier, Cockell, Simon, Tiniakos, Dina, Bedossa, Pierre, Burt, Alastair, Oakley, Fiona, Cordell, Heather J., Day, Christopher P., Wonders, Kristy, Missier, Paolo, Mcteer, Matthew, Vale, Luke, Oluboyede, Yemi, Breckons, Matt, Bossuyt, Patrick M., Zafarmand, Hadi, Vali, Yasaman, Lee, Jenny, Nieuwdorp, Max, Holleboom, Adriaan G., Verheij, Joanne, Ratziu, Vlad, Clément, Karine, Patino-Navarrete, Rafael, Pais, Raluca, Paradis, Valerie, Schuppan, Detlef, Schattenberg, Jörn M., Surabattula, Rambabu, Myneni, Sudha, Straub, Beate K., Vidal-Puig, Toni, Vacca, Michele, Rodrigues-Cuenca, Sergio, Allison, Mike, Kamzolas, Ioanni, Petsalaki, Evangelia, Campbell, Mark, Lelliott, Chris J., Davies, Susan, Orešič, Matej, Hyötyläinen, Tuulia, Mcglinchey, Aiden, Mato, Jose M., Millet, Óscar, Dufour, Jean-Françoi, Berzigotti, Annalisa, Masoodi, Mojgan, Pavlides, Michael, Harrison, Stephen, Neubauer, Stefan, Cobbold, Jeremy, Mozes, Ferenc, Akhtar, Salma, Olodo-Atitebi, Seliat, Banerjee, Rajarshi, Kelly, Matt, Shumbayawonda, Elizabeth, Dennis, Andrea, Andersson, Anneli, Wigley, Ioan, Romero-Gómez, Manuel, Gómez-González, Emilio, Ampuero, Javier, Castell, Javier, Gallego-Durán, Rocío, Fernández, Isabel, Montero-Vallejo, Rocío, Karsdal, Morten, Guldager Kring Rasmussen, Daniel, Leeming, Diana Julie, Sinisi, Antonia, Musa, Kishwar, Sandt, Estelle, Tonini, Manuela, Bugianesi, Elisabetta, Rosso, Chiara, Armandi, Angelo, Marra, Fabio, Gastaldelli, Amalia, Svegliati, Gianluca, Boursier, Jérôme, Francque, Sven, Vonghia, Luisa, Driessen, Ann, Ekstedt, Mattia, Kechagias, Stergio, Yki-Järvinen, Hannele, Porthan, Kimmo, Arola, Johanna, van Mil, Saskia, Papatheodoridis, George, Cortez-Pinto, Helena, Rodrigues, Cecilia M. P., Valenti, Luca, Pelusi, Serena, Petta, Salvatore, Pennisi, Grazia, Miele, Luca, Geier, Andrea, Trautwein, Christian, Aithal, Guruprasad P., Francis, Susan, Hockings, Paul, Schneider, Moritz, Newsome, Philip, Hübscher, Stefan, Wenn, David, Rosenquist, Christian, Trylesinski, Aldo, Mayo, Rebeca, Alonso, Cristina, Duffin, Kevin, Perfield, James W., Chen, Yu, Yunis, Carla, Tuthill, Theresa, Harrington, Magdalena Alicia, Miller, Melissa, Chen, Yan, Mcleod, Euan Jame, Ross, Trenton, Bernardo, Barbara, Schölch, Corinna, Ertle, Judith, Younes, Ramy, Oldenburger, Anouk, Ostroff, Rachel, Alexander, Leigh, Biegel, Hannah, Skalshøi Kjær, Mette, Mørch Harder, Lea, Davidsen, Peter, Mikkelsen, Lars Frii, Balp, Maria-Magdalena, Brass, Clifford, Jennings, Lori, Martic, Miljen, Löffler, Jürgen, Applegate, Dougla, Shankar, Sudha, Torstenson, Richard, Fournier-Poizat, Céline, Llorca, Anne, Kalutkiewicz, Michael, Pepin, Kay, Ehman, Richard, Horan, Gerald, Ho, Gideon, Tai, Dean, Chng, Elaine, Patterson, Scott D., Billin, Andrew, Doward, Lynda, Twiss, Jame, Thakker, Paresh, Landgren, Henrik, Lackner, Carolin, Gouw, Annette, Hytiroglou, Prodromos, Luca, Miele (ORCID:0000-0003-3464-0068), Jenny, Lee, Max, Westphal, Yasaman, Vali, Jerome, Boursier, Salvatorre, Petta, Rachel, Ostroff, Leigh, Alexander, Yu, Chen, Celine, Fournier, Andreas, Geier, Sven, Francque, Kristy, Wonder, Dina, Tiniako, Pierre, Bedossa, Mike, Allison, Georgios, Papatheodoridi, Helena, Cortez-Pinto, Raluca, Pai, Jean-Francois, Dufour, Diana Julie, Leeming, Stephen, Harrison, Jeremy, Cobbold, Adriaan G, Holleboom, Hannele, Yki-Järvinen, Javier, Crespo, Mattias, Ekstedt, Guruprasad P, Aithal, Elisabetta, Bugianesi, Manuel, Romero-Gomez, Richard, Torstenson, Morten, Karsdal, Carla, Yuni, Jörn M, Schattenberg, Detlef, Schuppan, Vlad, Ratziu, Clifford, Bra, Kevin, Duffin, Koos, Zwinderman, Michael, Pavlide, Quentin M, Anstee, Patrick M, Bossuyt, Anstee, Quentin M., Daly, Ann K., Govaere, Olivier, Cockell, Simon, Tiniakos, Dina, Bedossa, Pierre, Burt, Alastair, Oakley, Fiona, Cordell, Heather J., Day, Christopher P., Wonders, Kristy, Missier, Paolo, Mcteer, Matthew, Vale, Luke, Oluboyede, Yemi, Breckons, Matt, Bossuyt, Patrick M., Zafarmand, Hadi, Vali, Yasaman, Lee, Jenny, Nieuwdorp, Max, Holleboom, Adriaan G., Verheij, Joanne, Ratziu, Vlad, Clément, Karine, Patino-Navarrete, Rafael, Pais, Raluca, Paradis, Valerie, Schuppan, Detlef, Schattenberg, Jörn M., Surabattula, Rambabu, Myneni, Sudha, Straub, Beate K., Vidal-Puig, Toni, Vacca, Michele, Rodrigues-Cuenca, Sergio, Allison, Mike, Kamzolas, Ioanni, Petsalaki, Evangelia, Campbell, Mark, Lelliott, Chris J., Davies, Susan, Orešič, Matej, Hyötyläinen, Tuulia, Mcglinchey, Aiden, Mato, Jose M., Millet, Óscar, Dufour, Jean-Françoi, Berzigotti, Annalisa, Masoodi, Mojgan, Pavlides, Michael, Harrison, Stephen, Neubauer, Stefan, Cobbold, Jeremy, Mozes, Ferenc, Akhtar, Salma, Olodo-Atitebi, Seliat, Banerjee, Rajarshi, Kelly, Matt, Shumbayawonda, Elizabeth, Dennis, Andrea, Andersson, Anneli, Wigley, Ioan, Romero-Gómez, Manuel, Gómez-González, Emilio, Ampuero, Javier, Castell, Javier, Gallego-Durán, Rocío, Fernández, Isabel, Montero-Vallejo, Rocío, Karsdal, Morten, Guldager Kring Rasmussen, Daniel, Leeming, Diana Julie, Sinisi, Antonia, Musa, Kishwar, Sandt, Estelle, Tonini, Manuela, Bugianesi, Elisabetta, Rosso, Chiara, Armandi, Angelo, Marra, Fabio, Gastaldelli, Amalia, Svegliati, Gianluca, Boursier, Jérôme, Francque, Sven, Vonghia, Luisa, Driessen, Ann, Ekstedt, Mattia, Kechagias, Stergio, Yki-Järvinen, Hannele, Porthan, Kimmo, Arola, Johanna, van Mil, Saskia, Papatheodoridis, George, Cortez-Pinto, Helena, Rodrigues, Cecilia M. P., Valenti, Luca, Pelusi, Serena, Petta, Salvatore, Pennisi, Grazia, Miele, Luca, Geier, Andrea, Trautwein, Christian, Aithal, Guruprasad P., Francis, Susan, Hockings, Paul, Schneider, Moritz, Newsome, Philip, Hübscher, Stefan, Wenn, David, Rosenquist, Christian, Trylesinski, Aldo, Mayo, Rebeca, Alonso, Cristina, Duffin, Kevin, Perfield, James W., Chen, Yu, Yunis, Carla, Tuthill, Theresa, Harrington, Magdalena Alicia, Miller, Melissa, Chen, Yan, Mcleod, Euan Jame, Ross, Trenton, Bernardo, Barbara, Schölch, Corinna, Ertle, Judith, Younes, Ramy, Oldenburger, Anouk, Ostroff, Rachel, Alexander, Leigh, Biegel, Hannah, Skalshøi Kjær, Mette, Mørch Harder, Lea, Davidsen, Peter, Mikkelsen, Lars Frii, Balp, Maria-Magdalena, Brass, Clifford, Jennings, Lori, Martic, Miljen, Löffler, Jürgen, Applegate, Dougla, Shankar, Sudha, Torstenson, Richard, Fournier-Poizat, Céline, Llorca, Anne, Kalutkiewicz, Michael, Pepin, Kay, Ehman, Richard, Horan, Gerald, Ho, Gideon, Tai, Dean, Chng, Elaine, Patterson, Scott D., Billin, Andrew, Doward, Lynda, Twiss, Jame, Thakker, Paresh, Landgren, Henrik, Lackner, Carolin, Gouw, Annette, Hytiroglou, Prodromos, and Luca, Miele (ORCID:0000-0003-3464-0068)

Abstract

Background and aims: Detecting NASH remains challenging, while at-risk NASH (steatohepatitis and F≥ 2) tends to progress and is of interest for drug development and clinical application. We developed prediction models by supervised machine learning techniques, with clinical data and biomarkers to stage and grade patients with NAFLD. Approach and results: Learning data were collected in the Liver Investigation: Testing Marker Utility in Steatohepatitis metacohort (966 biopsy-proven NAFLD adults), staged and graded according to NASH CRN. Conditions of interest were the clinical trial definition of NASH (NAS ≥ 4;53%), at-risk NASH (NASH with F ≥ 2;35%), significant (F ≥ 2;47%), and advanced fibrosis (F ≥ 3;28%). Thirty-five predictors were included. Missing data were handled by multiple imputations. Data were randomly split into training/validation (75/25) sets. A gradient boosting machine was applied to develop 2 models for each condition: clinical versus extended (clinical and biomarkers). Two variants of the NASH and at-risk NASH models were constructed: direct and composite models.Clinical gradient boosting machine models for steatosis/inflammation/ballooning had AUCs of 0.94/0.79/0.72. There were no improvements when biomarkers were included. The direct NASH model produced AUCs (clinical/extended) of 0.61/0.65. The composite NASH model performed significantly better (0.71) for both variants. The composite at-risk NASH model had an AUC of 0.83 (clinical and extended), an improvement over the direct model. Significant fibrosis models had AUCs (clinical/extended) of 0.76/0.78. The extended advanced fibrosis model (0.86) performed significantly better than the clinical version (0.82). Conclusions: Detection of NASH and at-risk NASH can be improved by constructing independent machine learning models for each component, using only clinical predictors. Adding biomarkers only improved the accuracy of fibrosis.

Published
2023

10. Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance

Author

Chatzigeorgiou, Antonios, Seijkens, Tom, Zarzycka, Barbara, Engel, David, Poggi, Marjorie, van den Berg, Susan, van den Berg, Sjoerd, Soehnlein, Oliver, Winkels, Holger, Beckers, Linda, Lievens, Dirk, Driessen, Ann, Kusters, Pascal, Biessen, Erik, Garcia-Martin, Ruben, Amelna, Anne Klotzsche-von, Gijbels, Marion, Noelle, Randolph, Boon, Louis, Hackeng, Tilman, Schulte, Klaus, Xu, Aimin, Vriend, Gert, Nabuurs, Sander, Chung, Kyoung-Jin, van Dijk, Ko Willems, Rensen, Patrick C. N., Gerdes, Norbert, de Winther, Menno, Block, Norman L., Schally, Andrew V., Webere, Christian, Bornstein, Stefan R., Nicolaes, Gerry, Chavakis, Triantafyllos, and Lutgens, Esther

Published
2014

16. ECCO topical review optimising reporting in surgery, endoscopy, and histopathology collaboration between S-ECCO, EduCom, H-ECCO

Author

Adamina, Michel, Feakins, Roger, Iacucci, Marietta, Spinelli, Antonino, Cannatelli, Rosanna, D'Hoore, Andre, Driessen, Ann, Katsanos, Konstantinos, Mookhoek, Aart, Myrelid, Par, Pellino, Gianluca, Peros, Georgios, Tontini, Gian Eugenio, Tripathi, Monika, Yanai, Henit, and Svrcek, Magali

Subjects
reporting, Science & Technology, Gastroenterology & Hepatology, LONG-TERM, inflammatory bowel disease [IBD], CHRONIC ULCERATIVE-COLITIS, Endoscopy, MAGNETIC-RESONANCE ENTEROGRAPHY, CROHNS-DISEASE, COLORECTAL-CANCER, surgery, EVIDENCE-BASED CONSENSUS, pathology, SERRATED EPITHELIAL CHANGES, Human medicine, INTRAABDOMINAL SEPTIC COMPLICATIONS, Life Sciences & Biomedicine, POUCH-ANAL ANASTOMOSIS, INFLAMMATORY-BOWEL-DISEASE
Abstract

BACKGROUND AND AIMS: Diagnosis and management of inflammatory bowel diseases [IBD] requires a lifelong multidisciplinary approach. The quality of medical reporting is crucial in this context. The present topical review addresses the need for optimised reporting in endoscopy, surgery, and histopathology. METHODS: A consensus expert panel consisting of gastroenterologists, surgeons, and pathologists, convened by the European Crohn's and Colitis Organisation, performed a systematic literature review. The following topics were covered: in endoscopy: [i] general IBD endoscopy; [ii] disease activity and surveillance; [iii] endoscopy treatment in IBD; in surgery: [iv] medical history with surgical relevance, surgical indication, and strategy; [v] operative approach; [vi] intraoperative disease description; [vii] operative steps; in pathology: [viii] macroscopic assessment and interpretation of resection specimens; [ix] IBD histology, including biopsies, surgical resections, and neoplasia; [x] IBD histology conclusion and report. Statements were developed using a Delphi methodology incorporating two consecutive rounds. Current practice positions were set when ≥ 80% of participants agreed on a recommendation. RESULTS: Thirty practice positions established a standard terminology for optimal reporting in endoscopy, surgery, and histopathology. Assessment of disease activity, surveillance recommendations, advice to surgeons for operative indication and strategies, including margins and extent of resection, and diagnostic criteria of IBD, as well as guidance for the interpretation of dysplasia and cancer, were handled. A standardised report including a core set of items to include in each specialty report, was defined. CONCLUSIONS: Interdisciplinary high-quality care requires thorough and standardised reporting across specialties. This topical review offers an actionable framework and practice recommendations to optimise reporting in endoscopy, surgery, and histopathology. ispartof: JOURNAL OF CROHNS & COLITIS vol:15 issue:7 pages:1089-1105 ispartof: location:England status: published

Published
2021

17. Muscle fat content is strongly associated with NASH: a longitudinal study in patients with morbid obesity.

Author

UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Service de gastro-entérologie, Nachit, Maxime Younes, Kwanten, Wilhelmus J, Thissen, Jean-Paul, Op De Beeck, Bart, Van Gaal, Luc, Vonghia, Luisa, Verrijken, An, Driessen, Ann, Horsmans, Yves, Francque, Sven, Leclercq, Isabelle, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Service de gastro-entérologie, Nachit, Maxime Younes, Kwanten, Wilhelmus J, Thissen, Jean-Paul, Op De Beeck, Bart, Van Gaal, Luc, Vonghia, Luisa, Verrijken, An, Driessen, Ann, Horsmans, Yves, Francque, Sven, and Leclercq, Isabelle

Abstract

Studies exploring the relationship between muscle fat content and non-alcoholic fatty liver disease (NAFLD) are scarce. Herein, we aimed to evaluate the association of muscle mass and fatty infiltration with biopsy-assessed NAFLD in patients with obesity. At inclusion (n = 184) and 12 months after a dietary intervention (n = 15) or bariatric surgery (n = 24), we evaluated NAFLD by liver biopsy, and skeletal muscle mass index (SMI) by CT (CT-SMI) or bioelectrical impedance analysis (BIA-SMI). We developed an index to evaluate absolute fat content in muscle (skeletal muscle fat index [SMFI]) from CT-based psoas muscle density (SMFI). Muscle mass was higher in patients with NAFLD than in those without (CT-SMI 56.8 ± 9.9 vs. 47.4 ± 6.5 cm/m, p <0.0001). There was no association between sarcopenia and non-alcoholic steatohepatitis (NASH). SMFI was higher in NASH ≥F2 and early NASH F0-1 than in NAFL (78.5 ± 23.6 and 73.1 ± 15.6 vs. 61.2 ± 12.6, p <0.001). A 1-point change in the score for any of the individual cardinal NASH features (i.e. steatosis, inflammation or ballooning) was associated with an increase in SMFI (all p <0.05). The association between SMFI and NASH was highly significant even after adjustment for multiple confounders (all p <0.025). After intervention (n = 39), NASH improvement, defined by NAFLD activity score <3 or a 2-point score reduction, was achieved in more than 75% of patients (n = 25 or n = 27, respectively) that had pre-established NASH at inclusion (n = 32) and was associated with a significant decrease in SMFI (p <0.001). Strikingly, all patients who had ≥11% reduction in SMFI achieved NASH improvement (14/14, p <0.05). Muscle fat content, but not muscle mass, is strongly and independently associated with NASH. All individuals who achieved a ≥11% decrease in SMFI after intervention improved their NASH. These data indicate that muscle fatty infiltration could be a potential marker for (and perhaps a pathophysiological contributor to) NASH. Th

Published
2021

18. The clinical value of minimal invasive autopsy in COVID-19 patients

Author

D'ONOFRIO, Valentino, Donders, Elena, Vanden Abeele, Marie-Elena, Dubois, Jasperina, Cartuyvels, Reinoud, ACHTEN, Ruth, Lammens, Martin, Dendooven, Amelie, DRIESSEN, Ann, Augsburg, Lukasz, Vanrusselt, Jan, COX, Janneke, and Pasin, Laura

Subjects
Male, Viral Diseases, Pulmonology, Nosocomial Infections, Autopsy, Artificial Gene Amplification and Extension, Disease, Polymerase Chain Reaction, law.invention, Diagnostic Radiology, Medical Conditions, Belgium, law, Cause of Death, Medicine and Health Sciences, Prospective Studies, Medical diagnosis, Prospective cohort study, Cause of death, Multidisciplinary, Radiology and Imaging, Intensive care unit, Infectious Diseases, Oncology, Cohort, RNA, Viral, Medicine, Female, Coronavirus Infections, Engineering sciences. Technology, Research Article, medicine.medical_specialty, Imaging Techniques, Science, Pneumonia, Viral, Surgical and Invasive Medical Procedures, Research and Analysis Methods, Betacoronavirus, Diagnostic Medicine, Internal medicine, medicine, Cancer Detection and Diagnosis, Humans, Molecular Biology Techniques, Pandemics, Molecular Biology, ILL ICU PATIENTS, Aged, business.industry, SARS-CoV-2, COVID-19, Biology and Life Sciences, Covid 19, Pneumonia, Histopathology, business, Tomography, X-Ray Computed
Abstract

Background Minimally invasive autopsy (MIA) is a validated and safe method to establish the cause of death (COD), mainly in low-resource settings. However, the additional clinical value of MIA in Coronavirus disease (COVID-19) patients in a high-resource setting is unknown. The objective was to assess if and how MIA changed clinical COD and contributing diagnoses in deceased COVID-19 patients. Methods and findings A prospective observational cohort from April to May 2020 in a 981-bed teaching hospital in the epicenter of the COVID-19 pandemic in Belgium was established. Patients who died with either PCR-confirmed or radiologically confirmed COVID-19 infection were consecutively included. MIA consisted of whole-body CT and CT-guided Tru-Cut (R) biopsies. Diagnostic modalities were clinical chart review, radiology, microbiology, and histopathology which were assessed by two independent experts per modality. MIA COD and contributing diagnoses were established during a multi-disciplinary meeting. Clinical COD (CCOD) and contributing diagnosis were abstracted from the discharge letter. The main outcomes were alterations in CCOD and contributing diagnoses after MIA, and the contribution of each diagnostic modality. We included 18 patients, of which 7 after intensive care unit hospitalization. MIA led to an alteration in 15/18 (83%) patients. The CCOD was altered in 5/18 (28%) patients. MIA found a new COD (1/5), a more specific COD (1/5), a less certain COD (1/5), or a contributing diagnosis to be the COD (2/5). Contributing diagnoses were altered in 14/18 (78%) patients: 9 new diagnoses, 5 diagnoses dismissed, 3 made more specific, and 2 made less certain. Overall, histopathology contributed in 14/15 (93%) patients with alterations, radiology and microbiology each in 6/15 (40%), and clinical review in 3/15 (20%). Histopathology was deemed the most important modality in 10 patients, radiology in two patients, and microbiology in one patient. Conclusion MIA, especially histological examination, can add valuable new clinical information regarding the cause of death in COVID-19 patients, even in a high-resource setting with wide access to premortem diagnostic modalities. MIA may provide important clinical insights and should be applied in the current ongoing pandemic. This study/Janneke Cox has received funding from the Research Foundation Flanders (FWO) (G0G2620N). FWO.be. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study is part of the Limburg Clinical Research Center (LCRC) UHasselt-ZOL-Jessa, supported by the foundation Limburg Sterk Merk (LSM), Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital. Cox, J (corresponding author), Hasselt Univ, Fac Med & Life Sci, Hasselt, Belgium ; Jessa Hosp, Dept Infect Dis & Immun, Hasselt, Belgium janneke.cox@jessazh.be

Published
2020

19. Guidelines for an optimal management of a malignant colorectal polyp. What is essential in a pathology report ?

Author

Dano, H., Baldin, P., Demetter, P., Driessen, Ann, Hoorens, A., Sagaert, X., Van Huysse, J., Verset, L., Jouret-Mourin, A., UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Centre du cancer, and UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie

Subjects
lymphovascular permeation, depthinvasion, Colonic Polyps, Colonoscopy, micropapillary, tumour budding, Risk Factors, Practice Guidelines as Topic, degree of invasion, Humans, Human medicine, Colorectal Neoplasms, malignant polyp, depth invasion
Abstract

Colorectal cancer (CRC) has become the most common malignancy in our country. Routine screening colonoscopy is on the rise. With the recent advances in endoscopic treatment, many T1 colorectal carcinomas are now found and their percentage amenable to endoscopic resection has increased. Endoscopists and pathologists dealing with the steadily increasing number of excised colorectal polyps have to collaborate closely to optimize patient care. Therapeutic management of patients after endoscopic resection is based on precise histological criteria that determine the risk of metastasis and the need for complementary surgery. This paper summarizes the procedures for the macroscopic management of endoscopic excisions and presents the identified risk factors which should be included in a standardized pathology report. ispartof: ACTA GASTRO-ENTEROLOGICA BELGICA vol:83 issue:1 pages:53-59 ispartof: location:Belgium status: published

Published
2020

20. Risk of Development of More-advanced Lesions in Patients With Inflammatory Bowel Diseases and Dysplasia.

Author

UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'anatomie pathologique, UCL - (MGD) Service de gastro-entérologie, Cremer, Anneline, Demetter, Pieter, De Vos, Martine, Rahier, Jean-François, Baert, Filip, Moreels, Tom, Macken, Elisabeth, Louis, Edouard, Ferdinande, Liesbeth, Fervaille, Caroline, Dedeurwaerdere, Franceska, Bletard, Noela, Driessen, Ann, De Hertogh, Gert, Vermeire, Séverine, Franchimont, Denis, Belgian Inflammatory Bowel Disease Research and Development (BIRD) Group, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'anatomie pathologique, UCL - (MGD) Service de gastro-entérologie, Cremer, Anneline, Demetter, Pieter, De Vos, Martine, Rahier, Jean-François, Baert, Filip, Moreels, Tom, Macken, Elisabeth, Louis, Edouard, Ferdinande, Liesbeth, Fervaille, Caroline, Dedeurwaerdere, Franceska, Bletard, Noela, Driessen, Ann, De Hertogh, Gert, Vermeire, Séverine, Franchimont, Denis, and Belgian Inflammatory Bowel Disease Research and Development (BIRD) Group

Abstract

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 develo

Published
2020

21. Guidelines for an optimal management of a malignant colorectal polyp. What is essential in a pathology report ?

Author

UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Centre du cancer, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, Dano, Hélène, Baldin, Paméla, Demetter, Pieter, Driessen, Ann, Hoorens, Anne, Sagaert, Xavir, Van Huysse, Jacques, Verset, Laurine, Mourin, Anne, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Centre du cancer, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, Dano, Hélène, Baldin, Paméla, Demetter, Pieter, Driessen, Ann, Hoorens, Anne, Sagaert, Xavir, Van Huysse, Jacques, Verset, Laurine, and Mourin, Anne

Abstract

Colorectal cancer (CRC) has become the most common malignancy in our country. Routine screening colonoscopy is on the rise. With the recent advances in endoscopic treatment, many T1 colorectal carcinomas are now found and their percentage amenable to endoscopic resection has increased. Endoscopists and pathologists dealing with the steadily increasing number of excised colorectal polyps have to collaborate closely to optimize patient care. Therapeutic management of patients after endoscopic resection is based on precise histological criteria that determine the risk of metastasis and the need for complementary surgery. This paper summarizes the procedures for the macroscopic management of endoscopic excisions and presents the identified risk factors which should be included in a standardized pathology report.

Published
2020

22. Guidelines for an optimal management of a malignant Colorectal polyp. What is essential in a pathology report?

Author

Dano, Héléne, Baldin, Paméla, Demetter, Pieter, Driessen, Ann, Hoorens, Anne, Sagaert, Xavier, Van Huysse, Jacques, Verset, Laurine, Jouret-Mourin, Anne, Dano, Héléne, Baldin, Paméla, Demetter, Pieter, Driessen, Ann, Hoorens, Anne, Sagaert, Xavier, Van Huysse, Jacques, Verset, Laurine, and Jouret-Mourin, Anne

Abstract

Colorectal cancer (CRC) has become the most common malignancy in our country. Routine screening colonoscopy is on the rise. With the recent advances in endoscopic treatment, many T1 colorectal carcinomas are now found and their percentage amenable to endoscopic resection has increased. Endoscopists and pathologists dealing with the steadily increasing number of excised colorectal polyps have to collaborate closely to optimize patient care. Therapeutic management of patients after endoscopic resection is based on precise histological criteria that determine the risk of metastasis and the need for complementary surgery. This paper summarizes the procedures for the macroscopic management of endoscopic excisions and presents the identified risk factors which should be included in a standardized pathology report., SCOPUS: re.j, info:eu-repo/semantics/published

Published
2020

24. Non-Alcoholic Steatohepatitis Decreases Microsomal Liver Function in the Absence of Fibrosis

Author

Verlinden, Wim, primary, Van Mieghem, Eugénie, additional, Depauw, Laura, additional, Vanwolleghem, Thomas, additional, Vonghia, Luisa, additional, Weyler, Jonas, additional, Driessen, Ann, additional, Callens, Dirk, additional, Roosens, Laurence, additional, Dirinck, Eveline, additional, Verrijken, An, additional, Gaal, Luc Van, additional, and Francque, Sven, additional

Published
2020
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25. The clinical value of minimal invasive autopsy in COVID-19 patients

Author

D’Onofrio, Valentino, primary, Donders, Elena, additional, Vanden Abeele, Marie-Elena, additional, Dubois, Jasperina, additional, Cartuyvels, Reinoud, additional, Achten, Ruth, additional, Lammens, Martin, additional, Dendooven, Amelie, additional, Driessen, Ann, additional, Augsburg, Lukasz, additional, Vanrusselt, Jan, additional, and Cox, Janneke, additional

Published
2020
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27. 1836-P: Nonalcoholic Steatohepatitis (NASH) Significantly Contribute to ß-Cell Function Impairment Independently of Glucose Tolerance Status

Author

VONGHIA, LUISA, primary, DIRINCK, EVELINE, additional, CARLI, FABRIZIA, additional, VERRIJKEN, AN, additional, WEYLER, JONAS, additional, MICHIELSEN, PETER, additional, VANWOLLEGHEM, THOMAS, additional, DRIESSEN, ANN, additional, GAAL, LUC VAN, additional, FRANCQUE, SVEN, additional, DE BLOCK, CHRISTOPHE, additional, and GASTALDELLI, AMALIA, additional

Published
2020
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28. Nivolumab and anti-HCV activity, a case report

Author

Wuyts, Laura, primary, Janssens, Annelies, additional, Vonghia, Luisa, additional, Michielsen, Peter, additional, Raskin, Jo, additional, Driessen, Ann, additional, Van Hees, Stijn, additional, Francque, Sven, additional, and Vanwolleghem, Thomas, additional

Published
2020
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29. Studying the clinical, radiological, histological, microbiological, and immunological evolution during the different COVID-19 disease stages using minimal invasive autopsy.

Author

D'Onofrio, Valentino, Keulen, Lotte, Vandendriessche, Annelore, Dubois, Jasperina, Cartuyvels, Reinoud, Vanden Abeele, Marie-Elena, Fraussen, Judith, Vandormael, Patrick, Somers, Veerle, Achten, Ruth, Dendooven, Amélie, Driessen, Ann, Augsburg, Lukasz, Hellings, Niels, Lammens, Martin, Vanrusselt, Jan, and Cox, Janneke

Subjects
COVID-19, DISEASE progression, COVID-19 treatment, SARS-CoV-2
Abstract

The WHO defines different COVID-19 disease stages in which the pathophysiological mechanisms differ. We evaluated the characteristics of these COVID-19 disease stages. Forty-four PCR-confirmed COVID-19 patients were included in a prospective minimal invasive autopsy cohort. Patients were classified into mild-moderate (n = 4), severe-critical (n = 32) and post-acute disease (n = 8) and clinical, radiological, histological, microbiological and immunological data were compared. Classified according to Thoracic Society of America, patients with mild-moderate disease had no typical COVID-19 images on CT-Thorax versus 71.9% with typical images in severe-critical disease and 87.5% in post-acute disease (P < 0.001). Diffuse alveolar damage was absent in mild-moderate disease but present in 93.8% and 87.5% of patients with severe-critical and post-acute COVID-19 respectively (P = 0.002). Other organs with COVID-19 related histopathological changes were liver and heart. Interferon-γ levels were significantly higher in patients with severe-critical COVID-19 (P = 0.046). Anti-SARS CoV-2 IgG was positive in 66%, 40.6% and 87.5% of patients with mild-moderate, severe-critical and post-acute COVID-19 respectively (n.s.). Significant differences in histopathological and immunological characteristics between patients with mild-moderate disease compared to patients with severe-critical disease were found, whereas differences between patients with severe-critical disease and post-acute disease were limited. This emphasizes the need for tailored treatment of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Published
2022
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31. Risk of Development of More-advanced Lesions in Patients With Inflammatory Bowel Diseases and Dysplasia.

Author

Cremer, Anneline, Demetter, Pieter, De Vos, Martine, Rahier, Jean François, Baert, Filip, Moreels, Tom, Macken, Elisabeth, Louis, Edouard, Ferdinande, Liesbeth, Fervaille, Caroline, Dedeurwaerdere, Franceska, Bletard, Noela, Driessen, Ann, De Hertogh, Gert, Vermeire, Séverine, Franchimont, Denis, Belgian Inflammatory Bowel Disease Research and Development (BIRD) Group, Cremer, Anneline, Demetter, Pieter, De Vos, Martine, Rahier, Jean François, Baert, Filip, Moreels, Tom, Macken, Elisabeth, Louis, Edouard, Ferdinande, Liesbeth, Fervaille, Caroline, Dedeurwaerdere, Franceska, Bletard, Noela, Driessen, Ann, De Hertogh, Gert, Vermeire, Séverine, Franchimont, Denis, and Belgian Inflammatory Bowel Disease Research and Development (BIRD) Group

Abstract

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., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2019

33. The Belgian association for study of the liver guidance document on the management of adult and paediatric non-alcoholic fatty liver disease

Author

Francque, Sven, Cassiman, David, Smets, F., Komuta, Mina, Driessen, Ann, Dirinck, Eveline, Danse, Etienne, Op de Beeck, Beeck, van Craenenbroeck, Emeline, Van Nieuwenhove, Yves, Hubens, Guy, Lanthier, Nicolas, Geerts, Anja, Moreno, Christophe, Verbeke, Len, Reynaert, Hendrik, van Steenkiste, Christophe, Vonghia, Luisa, Kwanten, Wilhelmus W.J., Weyler, Joost, Trepo, Eric, Francque, Sven, Cassiman, David, Smets, F., Komuta, Mina, Driessen, Ann, Dirinck, Eveline, Danse, Etienne, Op de Beeck, Beeck, van Craenenbroeck, Emeline, Van Nieuwenhove, Yves, Hubens, Guy, Lanthier, Nicolas, Geerts, Anja, Moreno, Christophe, Verbeke, Len, Reynaert, Hendrik, van Steenkiste, Christophe, Vonghia, Luisa, Kwanten, Wilhelmus W.J., Weyler, Joost, and Trepo, Eric

Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD) is highly prevalent and associated with considerable liver-related and non-liverrelated morbidity and mortality. There is, however, a lot of uncertainty on how to handle NAFLD in clinical practice. The current guidance document, compiled under the aegis of the Belgian Association for the Study of the Liver by a panel of experts in NAFLD, from a broad range of different specialties, covers many questions encountered in daily clinical practice regarding diagnosis, screening, therapy and follow-up in adult and paediatric patients. Guidance statements in this document are based on the available evidence whenever possible. In case of absence of evidence or inconsistency of the data, guidance statements were formulated based on consensus of the expert panel. This guidance document is intended as a help for clinicians (general practitioners and all involved specialties) to implement the most recent evidence and insights in the field of NAFLD within a Belgian perspective., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2018

34. Interspecies NASH disease activity whole-genome profiling identifies a fibrogenic role of PPARα-regulated dermatopontin

Author

Lefebvre, Philippe, Lalloyer, Fanny, Baugé, Eric, Pawlak, Michal, Gheeraert, Céline, Dehondt, Hélène, Vanhoutte, Jonathan, Woitrain, Eloise, Hennuyer, Nathalie, Mazuy, Claire, Bobowski-Gérard, Marie, Zummo, Francesco Paolo, Derudas, Bruno, Driessen, Ann, Hubens, Guy, Vonghia, Luisa, Kwanten, Wilhelmus J., Michielsen, Peter, Vanwolleghem, Thomas, Eeckhoute, Jérôme, Verrijken, An, Van Gaal, Luc, Francque, Sven, and Staels, Bart

Subjects
Human medicine, Research Article
Abstract

Nonalcoholic fatty liver disease prevalence is soaring with the obesity pandemic, but the pathogenic mechanisms leading to the progression toward active nonalcoholic steatohepatitis (NASH) and fibrosis, major causes of liver-related death, are poorly defined. To identify key components during the progression toward NASH and fibrosis, we investigated the liver transcriptome in a human cohort of NASH patients. The transition from histologically proven fatty liver to NASH and fibrosis was characterized by gene expression patterns that successively reflected altered functions in metabolism, inflammation, and epithelial-mesenchymal transition. A meta-analysis combining our and public human transcriptomic datasets with murine models of NASH and fibrosis defined a molecular signature characterizing NASH and fibrosis and evidencing abnormal inflammation and extracellular matrix (ECM) homeostasis. Dermatopontin expression was found increased in fibrosis, and reversal of fibrosis after gastric bypass correlated with decreased dermatopontin expression. Functional studies in mice identified an active role for dermatopontin in collagen deposition and fibrosis. PPARα activation lowered dermatopontin expression through a transrepressive mechanism affecting the Klf6/TGFβ1 pathway. Liver fibrotic histological damages are thus characterized by the deregulated expression of a restricted set of inflammation- and ECM-related genes. Among them, dermatopontin may be a valuable target to reverse the hepatic fibrotic process.

Published
2017

35. Nivolumab and anti-HCV activity, a case report

Author

Wuyts, Laura, Janssens, Annelies, Vonghia, Luisa, Michielsen, Peter, Raskin, Jo, Driessen, Ann, Van Hees, Stijn, Francque, Sven, and Vanwolleghem, Thomas

Abstract

ABSTRACTExhaustion of antigen-specific T-cells in order to escape immune destruction is frequently seen in chronic viral infection and different types of cancer. Blockade of overexpressed negative co-stimulatory pathways, a process known as immune checkpoint modulation, is a promising novel therapy that could improve the treatment of liver diseases with features of T cell exhaustion. We present a case of a 54-year-old hepatitis C virus (HCV) positive patient with an acute flare of hepatitis during nivolumab treatment for a stage IV lung carcinoma, an anti-programmed death-1 (PD-1) immunotherapy. Retrospective testing of HCV RNA documented infection more than 6 months ago. Nivolumab treatment was associated with an alanine aminotransferase (ALT) flare reaching a peak value of 663 U/L, along with bilirubin levels of 0.74 mg/dL and no signs of coagulopathy. The assumption of a nivolumab-associated autoimmune hepatitis led to the interruption of the immune checkpoint inhibitor treatment. However, a subsequent 1-log decrease of HCV RNA load was noticed, which raised the possibility of an immune reconstitution against the HCV-infected hepatocytes with cell lysis. Liver biopsy specimen demonstrated no evidence for autoimmune liver disease or fibrosis. Clinical evolution was favorable and serum transaminases returned to normal levels and HCV RNA load increased to baseline values following nivolumab cessation. The current case suggests an anti-HCV activity of anti-PD-1 treatment in the setting of concomitant HCV viremia and lung carcinoma.

Published
2021
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38. Hepatocellular autophagy modulates the unfolded protein response and fasting-induced steatosis in mice

Author

Kwanten, Wilhelmus J., primary, Vandewynckel, Yves-Paul, additional, Martinet, Wim, additional, De Winter, Benedicte Y., additional, Michielsen, Peter P., additional, Van Hoof, Viviane O., additional, Driessen, Ann, additional, Timmermans, Jean-Pierre, additional, Bedossa, Pierre, additional, Van Vlierberghe, Hans, additional, and Francque, Sven M., additional

Published
2016
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39. Future remnant liver function estimated by combining liver volumetry on magnetic resonance imaging with total liver function on 99m Tc-mebrofenin hepatobiliary scintigraphy: can this tool predict post-hepatectomy liver failure?

Author

Chapelle, Thiery, primary, Op De Beeck, Bart, additional, Huyghe, Ivan, additional, Francque, Sven, additional, Driessen, Ann, additional, Roeyen, Geert, additional, Ysebaert, Dirk, additional, and De Greef, Kathleen, additional

Published
2016
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40. Endoscopic resection of two rare esophageal tumors

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Service de gastro-entérologie, Ooms, Hanne, Pelckmans, Paul A, Van Outryve, Steven, Driessen, Ann, Moreels, Tom, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Service de gastro-entérologie, Ooms, Hanne, Pelckmans, Paul A, Van Outryve, Steven, Driessen, Ann, and Moreels, Tom

Published
2015

41. Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance

Author

Dutch Heart Foundation, Netherlands Organisation for Health Research and Development, Alexander von Humboldt Foundation, German Research Foundation, European Research Council, Federal Ministry of Education and Research (Germany), German Center for Diabetes Research, German Centre for Cardiovascular Research, Cardiovascular Research Institute Maastricht, European Commission, Transnational University of Limburg, US Department of Veterans Affairs, Miller Institute for Basic Research in Science, Miami University, Chatzigeorgiou, Antonios, Seijkens, Tom, Zarzycka, Barbara, Engel, David, Poggi, Marjorie, van den Berg, Susan, van den Berg, Sjoerd, Soehnlein, Oliver, Winkels, Holger, Beckers, Linda, Lievens, Dirk, Driessen, Ann, Kusters, Pascal, Biessen, Erik, García-Martín, Rubén, Klotzsche-von Ameln, Anne, Gijbels, Marion, Noelle, Randolph, Boon, Louis, Hackeng, Tilman, Schulte, Klaus-Martin, Xu, Aimin, Vriend, Gert, Nabuurs, Sander, Chung, Kyoung-Jin, Willems van Dijk, Ko, Rensen, Patrick C N, Gerdes, Norbert, de Winther, Menno, Block, Norman L, Schally, Andrew V, Weber, Christian, Bornstein, Stefan R., Nicolaes, Gerry, Chavakis, Triantafyllos, Lutgens, Esther, Dutch Heart Foundation, Netherlands Organisation for Health Research and Development, Alexander von Humboldt Foundation, German Research Foundation, European Research Council, Federal Ministry of Education and Research (Germany), German Center for Diabetes Research, German Centre for Cardiovascular Research, Cardiovascular Research Institute Maastricht, European Commission, Transnational University of Limburg, US Department of Veterans Affairs, Miller Institute for Basic Research in Science, Miami University, Chatzigeorgiou, Antonios, Seijkens, Tom, Zarzycka, Barbara, Engel, David, Poggi, Marjorie, van den Berg, Susan, van den Berg, Sjoerd, Soehnlein, Oliver, Winkels, Holger, Beckers, Linda, Lievens, Dirk, Driessen, Ann, Kusters, Pascal, Biessen, Erik, García-Martín, Rubén, Klotzsche-von Ameln, Anne, Gijbels, Marion, Noelle, Randolph, Boon, Louis, Hackeng, Tilman, Schulte, Klaus-Martin, Xu, Aimin, Vriend, Gert, Nabuurs, Sander, Chung, Kyoung-Jin, Willems van Dijk, Ko, Rensen, Patrick C N, Gerdes, Norbert, de Winther, Menno, Block, Norman L, Schally, Andrew V, Weber, Christian, Bornstein, Stefan R., Nicolaes, Gerry, Chavakis, Triantafyllos, and Lutgens, Esther

Abstract

The immune system plays an instrumental role in obesity and insulin resistance. Here, we unravel the role of the costimulatory molecule CD40 and its signaling intermediates, TNF receptor-associated factors (TRAFs), in diet-induced obesity (DIO). Although not exhibiting increased weight gain, male CD40(-/-) mice in DIO displayed worsened insulin resistance, compared with wild-type mice. This worsening was associated with excessive inflammation of adipose tissue (AT), characterized by increased accumulation of CD8(+) T cells and M1 macrophages, and enhanced hepatosteatosis. Mice with deficient CD40-TRAF2/3/5 signaling in MHCII(+) cells exhibited a similar phenotype in DIO as CD40(-/-) mice. In contrast, mice with deficient CD40-TRAF6 signaling in MHCII(+) cells displayed no insulin resistance and showed a reduction in both AT inflammation and hepatosteatosis in DIO. To prove the therapeutic potential of inhibition of CD40-TRAF6 in obesity, DIO mice were treated with a small-molecule inhibitor that we designed to specifically block CD40-TRAF6 interactions; this compound improved insulin sensitivity, reduced AT inflammation, and decreased hepatosteatosis. Our study reveals that the CD40-TRAF2/3/5 signaling pathway in MHCII(+) cells protects against AT inflammation and metabolic complications associated with obesity whereas CD40-TRAF6 interactions in MHCII(+) cells aggravate these complications. Inhibition of CD40-TRAF6 signaling by our compound may provide a therapeutic option in obesity-associated insulin resistance.

Published
2014

42. Nodular Regenerative Hyperplasia Secondary to Neoadjuvant Chemotherapy for Colorectal Liver Metastases

Author

van den Broek, Maartje A. J., Olde Damink, Steven W. M., Driessen, Ann, Dejong, Cornelis H. C., and Bemelmans, Marc H. A.

Subjects
Article Subject
Abstract

Liver resection is the only curative treatment for patients with colorectal liver metastases (CLMs). Neoadjuvant chemotherapy can improve resectability but has a potential harmful effect on the nontumorous liver. Patients with chemotherapy-induced hepatic injury undergoing liver surgery have higher risks of post-resectional morbidity. We present two cases of patients without pre-existent liver disease treated with oxaliplatin-based chemotherapy followed by surgical resection of their CLMs. Their intra-operative liver specimen showed morphologic abnormalities characteristic of nodular regenerative hyperplasia (NRH). NRH led to portal hypertension in both patients that resulted in deleterious post-resectional complications and death of one patient. Interestingly, the other patient underwent two repeat nonanatomic liver resections because of recurrent CLMs. The intra-operative liver specimen still showed signs of NRH and sinusoidal congestion, but the post-resectional courses were uneventful. Nevertheless, caution is recommended in patients with suspected NRH. Careful volumetric analysis should guide the operative strategy. When future remnant liver volume is regarded insufficient, portal vein embolization or restrictive surgery should be considered.

Published
2009
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45. Abstract 611: Blocking CD40-TRAF6 Signaling is a Novel Therapeutic Target in Obesity-Associated Insulin Resistance

Author

Seijkens, Tom, primary, Chatzigeorgiou, Antonios, additional, Zarzycka, Barbara, additional, Engel, David, additional, Poggi, Marjorie, additional, van den Berg, Susan M, additional, van den Berg, Sjoerd A, additional, Soehnlein, Oliver, additional, Winkels, Holger, additional, Beckers, Linda, additional, Lievens, Dirk, additional, Driessen, Ann, additional, Kusters, Pascal, additional, Biessen, Erik, additional, Garcia Martin, Ruben, additional, Klotzsche-von Ameln, Anne, additional, Gijbels, Marion J, additional, Noelle, Randolph J, additional, Boon, Louis, additional, Hackeng, Tilman M, additional, Martin Schulte, Klaus, additional, Xu, Aimin, additional, Vriend, Gert, additional, Nabuurs, Sander B, additional, Chung, Kyoung-Jin, additional, Willems van Dijk, Ko, additional, Rensen, Patrick C, additional, Gerdes, Norbert, additional, de Winther, Menno P, additional, Block, Norman L, additional, Schally, Andrew W, additional, Weber, Christian, additional, Bornstein, Stefan R, additional, Nicolaes, Gerry A, additional, Chavakis, Triantafyllos, additional, and Lutgens, Esther, additional

Published
2014
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46. Severe steatosis induces portal hypertension by systemic arterial hyporeactivity and hepatic vasoconstrictor hyperreactivity in rats

Author

Graaff, Denise, Kwanten, Wilhelmus, Couturier, Filip, Govaerts, Jesse, Verlinden, Wim, Brosius, Isabel, D’Hondt, Michiel, Driessen, Ann, Winter, Benedicte, Man, Joris, Michielsen, Peter, and Francque, Sven

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease. The presence of portal hypertension has been demonstrated in NAFLD prior to development of inflammation or fibrosis, and is a result of extrahepatic and intrahepatic factors, principally driven by vascular dysfunction. An increased intrahepatic vascular resistance potentially contributes to progression of NAFLD via intralobular hypoxia. However, the exact mechanisms underlying vascular dysfunction in NAFLD remain unknown. This study investigates systemic hemodynamics and both aortic and intrahepatic vascular reactivity in a rat model of severe steatosis. Wistar rats were fed a methionine-choline-deficient diet, inducing steatosis, or control diet for 4 weeks. In vivo hemodynamic measurements, aortic contractility studies, and in situ liver perfusion experiments were performed. The mean arterial blood pressure was lower and portal blood pressure was higher in steatosis compared to controls. The maximal contraction force in aortic rings from steatotic rats was markedly reduced compared to controls. While blockade of nitric oxide (NO) production did not reveal any differences, cyclooxygenase (COX) blockade reduced aortic reactivity in both controls and steatosis, whereas effects were more pronounced in controls. Effects could be attributed to COX-2 iso-enzyme activity. In in situ liver perfusion experiments, exogenous NO donation or endogenous NO stimulation reduced the transhepatic pressure gradient (THPG), whereas NO synthase blockade increased the THPG only in steatosis, but not in controls. Alpha-1-adrenergic stimulation and endothelin-1 induced a significantly more pronounced increase in THPG in steatosis compared to controls. Our results demonstrate that severe steatosis, without inflammation or fibrosis, induces portal hypertension and signs of a hyperdynamic circulation, accompanied by extrahepatic arterial hyporeactivity and intrahepatic vascular hyperreactivity. The arterial hyporeactivity seems to be NO-independent, but appears to be mediated by specific COX-2-related mechanisms. Besides, the increased intrahepatic vascular resistance in steatosis appears not to be NO-related but rather to vasoconstrictor hyperreactivity. In this study, systemic hemodynamics and both aortic and intrahepatic vascular reactivity in a rat model of severe steatosis were investigated. Portal hypertension and signs of a hyperdynamic circulation were demonstrated. NO-independent, COX-2 mediated extrahepatic arterial hyporeactivity, as well as NO-independent alpha-1-adrenergic and endotheline-1 mediated intrahepatic vascular hyperreactivity are demonstrated, likely contributing to the observed portal hypertension in steatosis.

Published
2018
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47. Endogenous formation of Nε(carboxymethyl)lysine is increased in fatty livers and induces inflammatory markers in an in vitro model of hepatic steatosis

Author

Gaens, Katrien H. J., Gaens, Katrien H. J., Niessen, Petra M. G., Rensen, Sander S., Buurman, Wim A., Greve, Jan Willem M., Driessen, Ann, Wolfs, Marcel G. M., Hofker, Marten H., Bloemen, Johanne G., Dejong, Cornelis H., Stehouwer, Coen D. A., Schalkwijk, Casper G., Gaens, Katrien H. J., Gaens, Katrien H. J., Niessen, Petra M. G., Rensen, Sander S., Buurman, Wim A., Greve, Jan Willem M., Driessen, Ann, Wolfs, Marcel G. M., Hofker, Marten H., Bloemen, Johanne G., Dejong, Cornelis H., Stehouwer, Coen D. A., and Schalkwijk, Casper G.

Published
2012

48. Serrated polyps of the colon: how reproducible is their classification?

Author

UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service d'anatomie pathologique, Ensari, Arzu, Bilezikçi, Banu, Carneiro, Fatima, Doğusoy, Gülen Bülbül, Driessen, Ann, Dursun, Ayşe, Flejou, Jean-François, Geboes, Karel, de Hertogh, Gert, Mourin, Anne, Langner, Cord, Nagtegaal, Irıs D, Offerhaus, Johan, Orlowska, Janina, Ristimäki, Ari, Sanz-Ortega, Julian, Savaş, Berna, Sotiropoulou, Maria, Villanacci, Vincenzo, Kurşun, Nazmiye, Bosman, Fred, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service d'anatomie pathologique, Ensari, Arzu, Bilezikçi, Banu, Carneiro, Fatima, Doğusoy, Gülen Bülbül, Driessen, Ann, Dursun, Ayşe, Flejou, Jean-François, Geboes, Karel, de Hertogh, Gert, Mourin, Anne, Langner, Cord, Nagtegaal, Irıs D, Offerhaus, Johan, Orlowska, Janina, Ristimäki, Ari, Sanz-Ortega, Julian, Savaş, Berna, Sotiropoulou, Maria, Villanacci, Vincenzo, Kurşun, Nazmiye, and Bosman, Fred

Abstract

For several years, the lack of consensus on definition, nomenclature, natural history, and biology of serrated polyps (SPs) of the colon has created considerable confusion among pathologists. According to the latest WHO classification, the family of SPs comprises hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The term SSA/P with dysplasia has replaced the category of mixed hyperplastic/adenomatous polyps (MPs). The present study aimed to evaluate the reproducibility of the diagnosis of SPs based on currently available diagnostic criteria and interactive consensus development. In an initial round, H&E slides of 70 cases of SPs were circulated among participating pathologists across Europe. This round was followed by a consensus discussion on diagnostic criteria. A second round was performed on the same 70 cases using the revised criteria and definitions according to the recent WHO classification. Data were evaluated for inter-observer agreement using Kappa statistics. In the initial round, for the total of 70 cases, a fair overall kappa value of 0.318 was reached, while in the second round overall kappa value improved to moderate (kappa = 0.557; p < 0.001). Overall kappa values for each diagnostic category also significantly improved in the final round, reaching 0.977 for HP, 0.912 for SSA/P, and 0.845 for TSA (p < 0.001). The diagnostic reproducibility of SPs improves when strictly defined, standardized diagnostic criteria adopted by consensus are applied.

Published
2012

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