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2. International expert guidance for defining and monitoring small bowel strictures in Crohn's disease on intestinal ultrasound: a consensus statement

Author

Lu, Cathy, Rosentreter, Ryan, Parker, Claire E, Remillard, Julie, Wilson, Stephanie R, Baker, Mark E, Bhatnagar, Gauraang, Begun, Jakob, Bruining, David H, Bryant, Robert V, Christensen, Britt, Feagan, Brian G, Fletcher, Joel G, Gordon, Ilyssa, Henderson, Gaylyn, Jairath, Vipul, Knudsen, John, Kucharzik, Torsten, Lesack, Kyle, Maaser, Christian, Maconi, Giovanni, Novak, Kerri, Rimola, Jordi, Taylor, Stuart A, Wilkens, Rune, and Rieder, Florian

Published
2024
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5. Stricturing Crohn’s Disease Single-Cell RNA Sequencing Reveals Fibroblast Heterogeneity and Intercellular Interactions

Author

Mukherjee, Pranab K., Nguyen, Quang Tam, Li, Jiannan, Zhao, Shuai, Christensen, Stephen M., West, Gail A., Chandra, Jyotsna, Gordon, Ilyssa O., Lin, Sinan, Wang, Jie, Mao, Ren, Czarnecki, Douglas, Rayan, Carla, Goren, Idan, Banerjee, Suhanti, Kotak, Prerna, Plesec, Thomas, Lal, Samir, Fabre, Thomas, Asano, Shoh, Bound, Kathryn, Hart, Kevin, Park, Chanyoung, Martinez, Robert, Dower, Ken, Wynn, Thomas A., Hu, Shaomin, Naydenov, Nayden, Decaris, Martin, Turner, Scott, Holubar, Stefan D., Steele, Scott R., Fiocchi, Claudio, Ivanov, Andrei I., Kravarik, Kellie M., and Rieder, Florian

Published
2023
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6. HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44+ Natural Killer Cells in Ulcerative Colitis

Author

Akar, Alaa, Flemming, Cornelius, Felix, Flomm, Flosbach, Markus, Jäger, Julia, Jeromin, Niklas, Jung, Johannes, Ohms, Mareike, Reinshagen, Konrad, Rische, Johann, Sagebiel, Adrian, Sandfort, Deborah, Steinert, Fenja, Tomuschat, Christian, Wesche, Jasmin, Shifteh Abedian, Abraham, Clara, Achkar, Jean-Paul, Ahmad, Tariq, Alberts, Rudi, Alizadeh, Behrooz, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Anderson, Carl A., Andrews, Jane M., Annese, Vito, Aumais, Guy, Baidoo, Leonard, Baldassano, Robert N., Bampton, Peter A., Barclay, Murray, Barrett, Jeffrey C., Bethge, Johannes, Bewshea, Claire, Bis, Joshua C., Bitton, Alain, BK, Thelma, Boucher, Gabrielle, Brain, Oliver, Brand, Stephan, Brant, Steven R., Cheon, Jae Hee, Chew, Angela, Cho, Judy H., Cleynen, Isabelle, Cohain, Ariella, Cooney, Rachel, Croft, Anthony, Daly, Mark J., D'Amato, Mauro, Danese, Silvio, Daryani, Naser Ebrahim, Datta, Lisa Wu, Degenhardt, Frauke, Denapiene, Goda, Denson, Lee A., Devaney, Kathy L., Dewit, Olivier, D'Inca, Renata, Drummond, Hazel E., Dubinsky, Marla, Duerr, Richard H., Edwards, Cathryn, Ellinghaus, David, Ellul, Pierre, Esaki, Motohiro, Essers, Jonah, Ferguson, Lynnette R., Festen, Eleonora A., Fleshner, Philip, Florin, Tim, Franchimont, Denis, Franke, Andre, Fuyuno, Yuta, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Goyette, Philippe, Green, Todd, Griffiths, Anne M., Guthery, Stephen L., Hakonarson, Hakon, Halfvarson, Jonas, Hanigan, Katherine, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hayward, Nicholas K., Hedl, Matija, Henderson, Paul, Hold, Georgina L., Hong, Myhunghee, Hu, Xinli, Huang, Hailiang, Hugot, Jean-Pierre, Hui, Ken Y., Imielinski, Marcin, Jazayeri, Omid, Jonaitis, Laimas, Jostins, Luke, Juyal, Garima, Chandra Juyal, Ramesh, Kalla, Rahul, Karlsen, Tom H., Kennedy, Nicholas A., Khan, Mohammed Azam, Kim, Won Ho, Kitazono, Takanari, Kiudelis, Gediminas, Kubo, Michiaki, Kugathasan, Subra, Kupcinskas, Limas, Lamb, Christopher A., de Lange, Katrina M., Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lee, James C., Lees, Charlie W., Leja, Marcis, Lewis, Nina, Van Limbergen, Johan, Lionetti, Paolo, Liu, Jimmy Z., Louis, Edouard, Luo, Yang, Mahy, Gillian, Malekzadeh, Masoud Mohammad, Malekzadeh, Reza, Mansfield, John, Marriott, Suzie, Massey, Dunecan, Mathew, Christopher G., Matsui, Toshiyuki, McGovern, Dermot P.B., van der Meulen, Andrea, Midha, Vandana, Milgrom, Raquel, Mirzaei, Samaneh, Mitrovic, Mitja, Montgomery, Grant W., Mowat, Craig, Müller, Christoph, Newman, William G., Ng, Aylwin, Ng, Siew C., Evelyn Ng, Sok Meng, Nikolaus, Susanna, Ning, Kaida, Nöthen, Markus, Oikonomou, Ioannis, Okou, David, Orchard, Timothy R., Palmieri, Orazio, Parkes, Miles, Phillips, Anne, Ponsioen, Cyriel Y., Potocnik, Urõs, Poustchi, Hossein, Prescott, Natalie J., Proctor, Deborah D., Radford-Smith, Graham, Rahier, Jean- Francois, Regueiro, Miguel, Reinisch, Walter, Rieder, Florian, Rioux, John D., Roberts, Rebecca, Rogler, Gerhard, Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schadt, Eric E., Scharl, Michael, Schembri, John, Schreiber, Stefan, Schumm, L. Philip, Scott, Regan, Seielstad, Mark, Shah, Tejas, Sharma, Yashoda, Silverberg, Mark S., Simmons, Alison, Simms, Lisa A., Singh, Abhey, Skieceviciene, Jurgita, van Sommeren, Suzanne, Song, Kyuyoung, Sood, Ajit, Spain, Sarah L., Steinhart, A. Hillary, Stempak, Joanne M., Stronati, Laura, Sung, Joseph J.Y., Targan, Stephan R., Taylor, Kirstin M., Theatre, Emilie, Torkvist, Leif, Torres, Esther A., Tremelling, Mark, Uhlig, Holm H., Umeno, Junji, Vahedi, Homayon, Vasiliauskas, Eric, Velde, Anje ter, Ventham, Nicholas T., Vermeire, Severine, Verspaget, Hein W., De Vos, Martine, Walters, Thomas, Wang, Kai, Wang, Ming-Hsi, Weersma, Rinse K., Wei, Zhi, Whiteman, David, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Wong, Sunny H., Xavier, Ramnik J., Yamazaki, Keiko, Yang, Suk-Kyun, Ye, Byong Duk, Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhang, Hu, Zhang, Wei, Zhao, Hongyu, Zhao, Zhen Z., Baumdick, Martin E., Niehrs, Annika, Schwerk, Maria, Hinrichs, Ole, Jordan-Paiz, Ana, Padoan, Benedetta, Wegner, Lucy H.M., Schloer, Sebastian, Zecher, Britta F., Malsy, Jakob, Joshi, Vinita R., Illig, Christin, Schröder-Schwarz, Jennifer, Möller, Kimberly J., Martin, Maureen P., Yuki, Yuko, Ozawa, Mikki, Sauter, Jürgen, Schmidt, Alexander H., Perez, Daniel, Giannou, Anastasios D., Carrington, Mary, Davis, Randall S., Schumacher, Udo, Sauter, Guido, Huber, Samuel, Puelles, Victor G., Melling, Nathaniel, Altfeld, Marcus, and Bunders, Madeleine J.

Published
2023
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12. Human intestinal myofibroblasts deposited collagen VI enhances adhesiveness for T cells – A novel mechanism for maintenance of intestinal inflammation

Author

Lin, Si-Nan, Musso, Alessandro, Wang, Jie, Mukherjee, Pranab K., West, Gail A., Mao, Ren, Lyu, Ruishen, Li, Jiannan, Zhao, Shuai, Elias, Michael, Haberman, Yael, Denson, Lee A., Kugathasan, Subra, Chen, Min-Hu, Czarnecki, Doug, Dejanovic, Dina, Le, Hongnga T., Chandra, Jyotsna, Lipman, Jeremy, Steele, Scott R., Nguyen, Quang Tam, Fiocchi, Claudio, and Rieder, Florian

Published
2022
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13. Test Characteristics of Cross-sectional Imaging and Concordance With Endoscopy in Postoperative Crohn’s Disease

Author

Bachour, Salam P., Shah, Ravi S., Lyu, Ruishen, Nakamura, Takahiro, Shen, Michael, Li, Terry, Dane, Bari, Barnes, Edward L., Rieder, Florian, Cohen, Benjamin, Qazi, Taha, Lashner, Bret, Achkar, Jean Paul, Philpott, Jessica, Holubar, Stefan D., Lightner, Amy L., Regueiro, Miguel, Axelrad, Jordan, Baker, Mark E., and Click, Benjamin

Published
2022
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17. Serum Extracellular Matrix Molecules and Their Fragments as Biomarkers of Inflammation and Fibrosis in Inflammatory Bowel Diseases: A Systematic Review.

Author

Poulsen, Anja, Ovesen, Pernille Dige, Lu, Cathy, Bettenworth, Dominik, Jairath, Vipul, Feagan, Brian G, Seidelin, Jakob Benedict, and Rieder, Florian

Abstract

Background and Aim Contemporary techniques to assess disease activity or bowel damage in patients with inflammatory bowel disease [IBD], such as endoscopy and imaging, are either invasive or lack accuracy. Non-invasive biomarkers for this purpose remain an unmet medical need. Herein, we provide a comprehensive systematic review of studies evaluating blood extracellular matrix [ECM] biomarkers and their relevance in IBD. Methods We conducted a systematic review of PubMed, EMBASE, Web of Science, and Scopus to identify citations pertaining to ECM biomarkers of IBD up to March 1, 2024. Studies were categorized based on marker subtype and clinical use. Results Thirty-one ECM markers were identified, 28 of which demonstrated the ability to differentiate IBD disease activity. Collagen III emerged as the most extensively investigated [1212 IBD patients], with the degradation marker C3M and deposition marker PRO-C3 being associated with IBD and subtypes. Collagen V markers C5M and PRO-C5 emerged as the most accurate single markers for diagnosis of IBD, with an area under the curve of 0.91 and 0.93, respectively. Overall, studies were characterized by variable endpoints. None of the studies included histological grading of intestinal damage, repair, or fibrosis formation as the primary outcome in relation to the ECM blood markers. Conclusions Multiple ECM markers are linked with IBD and its phenotypes. However, more rigorous study designs and clearly defined endpoints are needed to ensure reproducibility and develop reliable and accurate biomarkers. ECM markers hold promise as they provide a 'window' into transmural tissue remodelling and fibrosis burden, warranting further investigation. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Radiomics to Detect Inflammation and Fibrosis on Magnetic Resonance Enterography in Stricturing Crohn's Disease.

Author

Chirra, Prathyush, Sleiman, Joseph, Gandhi, Namita S, Gordon, Ilyssa O, Hariri, Mohsen, Baker, Mark, Ottichilo, Ronald, Bruining, David H, Kurowski, Jacob A, Viswanath, Satish E, and Rieder, Florian

Abstract

Background and Aims Non-invasive cross-sectional imaging via magnetic resonance enterography [MRE] offers excellent accuracy for the diagnosis of stricturing complications in Crohn's disease [CD] but is limited in determining the degrees of fibrosis and inflammation within a stricture. We developed and validated a radiomics-based machine-learning model for separately characterizing the degree of histopathological inflammation and fibrosis in CD strictures and compared it to centrally read visual radiologist scoring of MRE. Methods This single-centre, cross-sectional study included 51 CD patients [ n  = 34 for discovery; n  = 17 for validation] with terminal ileal strictures confirmed on diagnostic MRE within 15 weeks of resection. Histopathological specimens were scored for inflammation and fibrosis and spatially linked with corresponding pre-surgical MRE sequences. Annotated stricture regions on MRE were scored visually by radiologists as well as underwent 3D radiomics-based machine learning analysis; both were evaluated against histopathology. Results Two distinct sets of radiomic features capturing textural heterogeneity within strictures were linked with each of severe inflammation or severe fibrosis across both the discovery (area under the curve [AUC = 0.69, 0.83] and validation [AUC = 0.67, 0.78] cohorts. Radiologist visual scoring had an AUC = 0.67 for identifying severe inflammation and AUC = 0.35 for severe fibrosis. Use of combined radiomics and radiologist scoring robustly augmented identification of severe inflammation [AUC = 0.79] and modestly improved assessment of severe fibrosis [AUC = 0.79 for severe fibrosis] over individual approaches. Conclusions Radiomic features of CD strictures on MRE can accurately identify severe histopathological inflammation and severe histopathological fibrosis, as well as augment performance of the radiologist visual scoring in stricture characterization. [ABSTRACT FROM AUTHOR]

Published
2024
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21. The Origin and Contribution of Cancer-Associated Fibroblasts in Colorectal Carcinogenesis

Author

Kobayashi, Hiroki, Gieniec, Krystyna A., Lannagan, Tamsin R.M., Wang, Tongtong, Asai, Naoya, Mizutani, Yasuyuki, Iida, Tadashi, Ando, Ryota, Thomas, Elaine M., Sakai, Akihiro, Suzuki, Nobumi, Ichinose, Mari, Wright, Josephine A., Vrbanac, Laura, Ng, Jia Q., Goyne, Jarrad, Radford, Georgette, Lawrence, Matthew J., Sammour, Tarik, Hayakawa, Yoku, Klebe, Sonja, Shin, Alice E., Asfaha, Samuel, Bettington, Mark L., Rieder, Florian, Arpaia, Nicholas, Danino, Tal, Butler, Lisa M., Burt, Alastair D., Leedham, Simon J., Rustgi, Anil K., Mukherjee, Siddhartha, Takahashi, Masahide, Wang, Timothy C., Enomoto, Atsushi, Woods, Susan L., and Worthley, Daniel L.

Published
2022
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24. An International Consensus to Standardize Integration of Histopathology in Ulcerative Colitis Clinical Trials

Author

Ma, Christopher, Sedano, Rocio, Almradi, Ahmed, Vande Casteele, Niels, Parker, Claire E., Guizzetti, Leonardo, Schaeffer, David F., Riddell, Robert H., Pai, Reetesh K., Battat, Robert, Sands, Bruce E., Rosty, Christophe, Dubinsky, Marla C., Rieder, Florian, Harpaz, Noam, Abreu, Maria T., Bryant, Robert V., Lauwers, Gregory Y., Kirsch, Richard, Valasek, Mark A., Crowley, Eileen, Sandborn, William J., Feagan, Brian G., Pai, Rish K., and Jairath, Vipul

Published
2021
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25. Development and Validation of a Novel Computed-Tomography Enterography Radiomic Approach for Characterization of Intestinal Fibrosis in Crohn’s Disease

Author

Li, Xuehua, Liang, Dong, Meng, Jixin, Zhou, Jie, Chen, Zhao, Huang, Siyun, Lu, Baolan, Qiu, Yun, Baker, Mark E., Ye, Ziyin, Cao, Qinghua, Wang, Mingyu, Yuan, Chenglang, Chen, Zhihui, Feng, Shengyu, Zhang, Yuxuan, Iacucci, Marietta, Ghosh, Subrata, Rieder, Florian, Sun, Canhui, Chen, Minhu, Li, Ziping, Mao, Ren, Huang, Bingsheng, and Feng, Shi-Ting

Published
2021
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27. Management of complications in patients with an ileostomy: an umbrella review of systematic reviews for the EndOTrial Consortium.

Author

Solitano, Virginia, Vuyyuru, Sudheer Kumar, Yuan, Yuhong, Singh, Siddharth, Narula, Neeraj, Ma, Christopher, Hanzel, Jurij, Hutton, Megan, Van Koughnett, Julie Ann, Rieder, Florian, and Jairath, Vipul

Subjects
CROHN'S disease, INFLAMMATORY bowel diseases, OSTOMATES, CLINICAL medicine, SKIN care, NURSING interventions
Abstract

Background: Standardized clinical care processes for patients with Crohn's disease (CD) and a permanent ileostomy (PI) are lacking. The EndOTrial consortium aims to address this gap by developing pathways for care. Methods: In this umbrella review, we searched major databases for relevant systematic reviews (SRs) or scoping reviews (ScR) published until January 5, 2024. Screening, data extraction, and quality appraisal (AMSTAR 2) were performed by two independent reviewers. Results: Of 1349 screened papers, 22 reviews met our inclusion criteria, including 20 SRs (eight with meta-analysis) and 2 ScRs. None exclusively focused on PI. Furthermore, nine reviews did not mention patients with inflammatory bowel disease (IBD), and only two reviews included patients with high-output ileostomy, highlighting a large evidence gap. The identified reviews covered six categories with nine types of interventions, including ostomy care pathways, peristomal skin care, patient education, clinical management of high-output stoma, management and prevention of postoperative ileus, dietary and nutritional support, nursing and supporting care, telemedicine, and self-management interventions. Most SRs including nursing interventions for stoma care highlighted nurses' role in a variety of standard and specialized treatments. Notably, none of the reviews exclusively examined disease recurrence, stoma pouching systems or adhesives, behavioral interventions, or mental health in patients living with ileostomy. Conclusions: Evidence for best practice interventions to treat complications and improve quality of life in patients living with an ileostomy for CD is limited and heterogeneous. These results outline the need for standardized clinical care processes and pathways tailored to the unique needs of this patient population. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Three-dimensional Pouchography: A Proof-of-concept Study of a Breakthrough Technique for Visualising Ileoanal Pouch Anatomy and Morphology in Normal and Mechanical Pouch Complication Patients.

Author

Holubar, Stefan D, Nachand, Douglas, Lavryk, Olga, Belkovsky, Mikhael, Brienza, Rita, Mohammed, Nour, Ream, Justin, Hull, Tracy, Steele, Scott R, Regueiro, Miguel, Cohen, Benjamin L, Qazi, Taha, and Rieder, Florian

Abstract

Background Herein, we present a proof-of-concept study of three-dimensional [3D] pouchography using virtual and printed 3D models of ileal pouch-anal anastomosis [IPAA] in patients with normal pouches and in cases of mechanical pouch complications. Methods We performed a retrospective, descriptive case series of a convenience sample of 10 pouch patients with or without pouch dysfunction, who had CT scans appropriate for segmentation who were identified from our pouch registry. The steps involved in clinician-driven automated 3D reconstruction are presented. Results We included three normal patients who underwent CT imaging and were found to have no primary pouch pathology, and seven patients with known pouch pathology identifiable with 3D reconstruction [including pouch strictures, megapouch, pouch volvulus, and twisted pouches], underwent 3D virtual modelling; one normal and one twisted pouch were 3D-printed. We discovered that 3D pouchography reliably identified staple lines [pouch body, anorectal circular and transverse, and tip of J], the relationship between staple lines, and variations in pouch morphology and pouch pathology. Conclusion Three-dimensional reconstruction of IPAA morphology is highly feasible using readily available technology. In our practice, we have found 3D pouchography to be an extremely useful adjunct to diagnose various mechanical pouch complications and improve planning for pouch salvage strategies. Given its ease of use and helpfulness in understanding the pouch structure and function, we have started to routinely integrate 3D pouchography into our clinical pouch referral practice. Further study is needed to formally assess the value of this technique to aid in the diagnosis of pouch pathology. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Muscular hyperplasia in Crohn's disease strictures: through thick and thin.

Author

Veisman, Ido, Massey, William J., Goren, Idan, Liu, Weiwei, Chauhan, Gaurav, and Rieder, Florian

Subjects
CROHN'S disease, SMOOTH muscle, MUSCLE cells, GASTROINTESTINAL system, DRUG target
Abstract

Fibrostenosing Crohn's disease (CD) represents a challenging clinical condition characterized by the development of symptomatic strictures within the gastrointestinal tract. Despite therapeutic advancements in managing inflammation, the progression of fibrostenotic complications remains a significant concern, often necessitating surgical intervention. Recent investigations have unveiled the pivotal role of smooth muscle cell hyperplasia in driving luminal narrowing and clinical symptomatology. Drawing parallels to analogous inflammatory conditions affecting other organs, such as the airways and blood vessels, sheds light on common underlying mechanisms of muscular hyperplasia. This review synthesizes current evidence to elucidate the mechanisms underlying smooth muscle cell proliferation in CD-associated strictures, offering insights into potential therapeutic targets. By highlighting the emerging significance of muscle thickening as a novel therapeutic target, this review aims to inform future research endeavors and clinical strategies with the goal to mitigate the burden of fibrostenotic complications in CD and other conditions. [ABSTRACT FROM AUTHOR]

Published
2024
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32. Preventing fibrosis in IBD: update on immune pathways and clinical strategies.

Author

Wang, Jie, Yang, Bo, Chandra, Jyotsna, Ivanov, Andrei, Brown, J. Mark, and Rieder, Florian

Subjects
CROHN'S disease, INFLAMMATORY bowel diseases, FIBROSIS, ULCERATIVE colitis, CLINICAL drug trials
Abstract

Intestinal fibrosis is a common and serious complication of inflammatory bowel diseases (IBD) driving stricture formation in Crohn's disease patients and leading to submucosal damage in ulcerative colitis. Recent studies provided novel insights into the role of immune and nonimmune components in the pathogenesis of intestinal fibrosis. Those new findings may accelerate the development of anti-fibrotic treatment in IBD patients. This review is designed to cover the recent progress in mechanistic research and therapeutic developments on intestinal fibrosis in IBD patients, including new cell clusters, cytokines, proteins, microbiota, creeping fat, and anti-fibrotic therapies. Due to the previously existing major obstacle of missing consensus on stricture definitions and the absence of clinical trial endpoints, testing of drugs with an anti-fibrotic mechanism is just starting in stricturing Crohn's disease (CD). A biomarker to stratify CD patients at diagnosis without any complications into at-risk populations for future strictures would be highly desirable. Further investigations are needed to identify novel mechanisms of fibrogenesis in the intestine that are targetable and ideally gut specific. [ABSTRACT FROM AUTHOR]

Published
2024
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34. Collagenous Colitis Is Associated With HLA Signature and Shares Genetic Risks With Other Immune-Mediated Diseases

Author

Stahl, Eli, Roda, Giulia, Dobbyn, Amanda, Hu, Jianzhong, Zhang, Zhongyang, Westerlind, Helga, Bonfiglio, Ferdinando, Raj, Towfique, Torres, Joana, Chen, Anli, Petras, Robert, Pardi, Darrell S., Iuga, Alina C., Levi, Gabriel S., Cao, Wenqing, Jain, Prantesh, Rieder, Florian, Gordon, Ilyssa O., Cho, Judy H., D’Amato, Mauro, Harpaz, Noam, Hao, Ke, Colombel, Jean Frederic, and Peter, Inga

Published
2020
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35. Selective deletion of MyD88 signaling in α-SMA positive cells ameliorates experimental intestinal fibrosis via post-transcriptional regulation

Author

Zhao, Shuai, Dejanovic, Dina, Yao, Peng, Bhilocha, Shardul, Sadler, Tammy, Schirbel, Anja, West, Gail, Doyon, Genevieve, Lopez, Rocio, Mao, Ren, Kurada, Satya, El Ouali, Sara, Grassl, Guntram, Fox, Paul L., Cruise, Michael, Worthley, Daniel L., de la Motte, Carol, Fiocchi, Claudio, and Rieder, Florian

Published
2020
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36. Histopathology Scoring Systems of Stenosis Associated With Small Bowel Crohn’s Disease: A Systematic Review

Author

Gordon, Ilyssa O., Bettenworth, Dominik, Bokemeyer, Arne, Srivastava, Amitabh, Rosty, Christophe, de Hertogh, Gert, Robert, Marie E., Valasek, Mark A., Mao, Ren, Kurada, Satya, Harpaz, Noam, Borralho, Paula, Pai, Reetesh K., Pai, Rish K., Odze, Robert, Feakins, Roger, Parker, Claire E., Nguyen, Tran, Jairath, Vipul, Baker, Mark E., Bruining, David H., Fletcher, J.G., Feagan, Brian G., and Rieder, Florian

Published
2020
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37. Fibrosis: from mechanisms to medicines

Author

Henderson, Neil C., Rieder, Florian, and Wynn, Thomas A.

Subjects
Fibrosis -- Development and progression -- Drug therapy, Pathology, Molecular -- Methods, Wounds and injuries -- Care and treatment, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Fibrosis can affect any organ and is responsible for up to 45% of all deaths in the industrialized world. It has long been thought to be relentlessly progressive and irreversible, but both preclinical models and clinical trials in various organ systems have shown that fibrosis is a highly dynamic process. This has clear implications for therapeutic interventions that are designed to capitalize on this inherent plasticity. However, despite substantial progress in our understanding of the pathobiology of fibrosis, a translational gap remains between the identification of putative antifibrotic targets and conversion of this knowledge into effective treatments in humans. Here we discuss the transformative experimental strategies that are being leveraged to dissect the key cellular and molecular mechanisms that regulate fibrosis, and the translational approaches that are enabling the emergence of precision medicine-based therapies for patients with fibrosis. This review discusses how single-cell profiling and other technological advances are increasing our understanding of the mechanisms of fibrosis, thereby accelerating the discovery, development and testing of new treatments., Author(s): Neil C. Henderson [sup.1] [sup.2] , Florian Rieder [sup.3] [sup.4] , Thomas A. Wynn [sup.5] Author Affiliations: (1) University of Edinburgh Centre for Inflammation Research, The Queen's Medical Research [...]

Published
2020
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40. Efficacy of Endoscopic Dilation of Gastroduodenal Crohn’s Disease Strictures: A Systematic Review and Meta-Analysis of Individual Patient Data

Author

Bettenworth, Dominik, Mücke, Marcus M., Lopez, Rocio, Singh, Amandeep, Zhu, Weiming, Guo, Feilong, Matsui, Toshiyuki, James, Theodore W., Herfarth, Hans, Goetz, Martin, Mao, Ren, Kurada, Satya, Hampe, Jochen, Matthes, Katja, Karstensen, John Gásdal, Valli, Piero V., Duijvestein, Marjolijn, D’Haens, Geert, Jairath, Vipul, Qiu, Tian Bai, Ding, Nik Sheng, Rogler, Gerhard, and Rieder, Florian

Published
2019
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45. Risankizumab Induction Therapy Achieves Early Symptom Improvements That Are Associated With Future Clinical and Endoscopic Outcomes in Crohn's Disease: Post Hoc Analysis of the ADVANCE, MOTIVATE, and FORTIFY Phase 3 Studies.

Author

Colombel, Jean-Frederic, Schreiber, Stefan, D'Haens, Geert, Rizzo, Joanne, Kligys, Kristina, Griffith, Jenny, Zambrano, Javier, Zhou, Qian, Zhang, Yafei, Kalabic, Jasmina, Rieder, Florian, Dubinsky, Marla C, and Panaccione, Remo

Abstract

Background and Aims Crohn's disease [CD] symptoms are a main driver for impaired quality of life, and fast relief is important for patient care. Stool frequency [SF] and abdominal pain score [APS] are patient-reported outcomes [PROs] measuring symptom severity, which are supported as treatment targets by the STRIDE-II consensus. This post hoc analysis examined the efficacy of risankizumab [RZB], a humanised monoclonal antibody with high specificity for interleukin-23 p19, for providing early symptom relief, along with the prognostic value of early symptom relief for achieving future clinical and endoscopic endpoints. Methods Individual and combined measures of SF and AP at Weeks 1, 2, and 3 were assessed in patients with moderate to severe CD who received 600 mg intravenous RZB or placebo [PBO] in the ADVANCE or MOTIVATE induction studies. Multivariate logistic regression was used to examine the predictiveness of early symptom improvement for clinical and endoscopic outcomes following RZB induction and maintenance. Results Higher rates of SF/APS clinical remission and enhanced clinical response were observed as early as Week 1 with RZB vs PBO. A larger proportion of patients achieved clinical endpoints with RZB vs PBO, irrespective of prior bio-failure status. Early PRO improvement was associated with a greater likelihood of achieving clinical and endoscopic improvement following 12-week induction and 52-week maintenance RZB dosing. Conclusions After the first intravenous RZB induction dose, significantly greater rates of symptom improvement vs PBO were achieved. Improvements could be observed as early as Week 1 and were predictive of Weeks 12 and 52 clinical and endoscopic improvement. [ABSTRACT FROM AUTHOR]

Published
2024
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47. The Safety, Tolerability, Pharmacokinetics, and Clinical Efficacy of the NLRX1 agonist NX-13 in Active Ulcerative Colitis: Results of a Phase 1b Study.

Author

Verstockt, Bram, Vermeire, Severine, Peyrin-Biroulet, Laurent, Mosig, Rebecca, Feagan, Brian G, Colombel, Jean-Frederic, Siegmund, Britta, Rieder, Florian, Schreiber, Stefan, Yarur, Andres, Panaccione, Remo, Dubinsky, Marla, Lichtiger, Simon, Cataldi, Fabio, and Danese, Silvio

Abstract

Background and Aims NX-13 activation of NLRX1 reduces intracellular reactive oxygen species and decreases inflammation in animal models of colitis. A phase 1a trial demonstrated a gut-selective pharmacokinetic profile with good tolerability. This phase Ib study aimed to evaluate the safety, tolerability, and pharmacokinetics of NX-13 in patients with active ulcerative colitis [UC]. Methods We conducted a multicentre, randomized, double-blind, placebo-controlled trial of NX-13 in patients with active UC. Patients with a Mayo Clinic Score of 4–10 were randomly assigned [3:3:3:1 ratio] to three NX-13 oral dose groups (250 mg immediate release [IR], 500 mg IR, or 500 mg delayed release [DR], or placebo) once daily for 4 weeks. Safety and pharmacokinetics were the primary and secondary objectives, respectively. Results Thirty-eight patients [11 females] were recruited and randomized to placebo [five], NX-13 250 mg IR [11], NX-13 500 mg IR [11], or NX-13 500 mg DR [11] and received at least one dose. There were no serious adverse events or deaths during the trial. One patient [500 mg DR, 1/11] withdrew due to worsening of UC and a second [500 mg IR, 1/11] on the last day of treatment after a panic attack associated with atrial fibrillation. In the efficacy population [36 patients], clinical improvement in rectal bleeding and stool frequency scores relative to placebo were seen as early as week 2 and endoscopic response was seen at week 4. Conclusions NX-13 was generally safe and well tolerated with early signs of rapid symptom and endoscopic improvement. This novel mechanism of action warrants further investigation. ClinicalTrials.gov: NCT04862741. [ABSTRACT FROM AUTHOR]

Published
2024
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48. Fibrosis in IBD: from pathogenesis to therapeutic targets.

Author

Rieder, Florian, Mukherjee, Pranab K., Massey, William J., Yan Wang, and Fiocchi, Claudio

Subjects
FIBROSIS, TYPHOID fever, INFLAMMATORY bowel diseases, DRUG target, FIBRONECTINS, TRANSFORMING growth factors, CROHN'S disease, SALMONELLA enterica serovar typhimurium, TRANSFORMING growth factors-beta
Published
2024
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