128 results on '"Rieder F"'
Search Results
2. Letter: volatile metabolomics of exhaled breath or faecal gas? – authorsʼ reply
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Kurada, S., Alkhouri, N., Fiocchi, C., Dweik, R., and Rieder, F.
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- 2015
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3. Review article: breath analysis in inflammatory bowel diseases
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Kurada, S., Alkhouri, N., Fiocchi, C., Dweik, R., and Rieder, F.
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- 2015
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- View/download PDF
4. The cytomegalovirus protein pUL32 is highly conserved among clinical strains although a major target of the humoral and cellular immune response: O394
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Vanura, K., Rieder, F., Kastner, M., Sandhofer, M., Le, T., Stral, R., Puchhammer, E., Steininger, C., Stamatopoulos, K., Graninger, W., and Jäger, U.
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- 2012
5. IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
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Momozawa, Y, Dmitrieva, J, Theatre, E, Deffontaine, V, Rahmouni, S, Charloteaux, B, Crins, F, Docampo, E, Elansary, M, Gori, AS, Lecut, C, Mariman, R, Mni, M, Oury, C, Altukhov, I, Alexeev, D, Aulchenko, Y, Amininejad, L, Bouma, G, Hoentjen, F, Lowenberg, M, Oldenburg, B, Pierik, MJ, de Jong, AE, van der Woude, C.J., Visschedijk, MC, Lathrop, M, Hugot, JP, Weersma, RK, Vos, M, Franchimont, D, Vermeire, S, Kubo, M, Louis, E, Georges, M, Abraham, C, Achkar, JP, Ahmad, T, Ananthakrishnan, AN, Andersen, V, Anderson, CA, Andrews, JM, Annese, V, Aumais, G, Baidoo, L, Baldassano, RN, Bampton, PA, Barclay, M, Barrett, JC, Bayless, TM, Bethge, J, Bitton, A, Boucher, G, Brand, S, Brandt, B, Brant, SR, Buning, C, Chew, A, Cho, JH, Cleynen, I, Cohain, A, Croft, A, Daly, MJ, D'Amato, M, Danese, S, Jong, D, Denapiene, G, Denson, LA, Devaney, KL, Dewit, O, D'Inca, R, Dubinsky, M, Duerr, RH, Edwards, C, Ellinghaus, D, Essers, J, Ferguson, LR, Festen, EA, Fleshner, P, Florin, T, Franke, A, Fransen, K, Gearry, R, Gieger, C, Glas, J, Goyette, P, Green, T, Griffiths, AM, Guthery, SL, Hakonarson, H, Halfvarson, J, Hanigan, K, Haritunians, T, de Hart, A, Hawkey, C, Hayward, NK, Hedl, M, Henderson, P, Hu, XH, Huang, HL, Hui, KY, Imielinski, M, Ippoliti, A, Jonaitis, L, Jostins, L, Karlsen, TH, Kennedy, NA, Khan, MA, Kiudelis, G, Krishnaprasad, K, Kugathasan, S, Kupcinskas, L, Latiano, A, Laukens, D, Lawrance, IC, Lee, JC, Lees, CW, Leja, M, van Limbergen, J, Lionetti, P, Liu, JZ, Mahy, G, Mansfield, J, Massey, D, Mathew, CG, McGovern, DPB, Milgrom, R, Mitrovic, M, Montgomery, GW, Mowat, C, Newman, W, Ng, A, Ng, SC, Ng, SME, Nikolaus, S, Ning, K, Nothen, M, Oikonomou, I, Palmieri, O, Parkes, M, Phillips, A, Ponsioen, CY, Potocnik, U, Prescott, NJ, Proctor, DD, Radford-Smith, G, Rahier, JF, Raychaudhuri, S, Regueiro, M, Rieder, F, Rioux, JD, Ripke, S, Roberts, R, Russell, RK, Sanderson, JD, Sans, M, Satsangi, J, Schadt, EE, Schreiber, S, Schulte, D, Schumm, LP, Scott, R, Seielstad, M, Sharma, Y, Silverberg, MS, Simms, LA, Skieceviciene, J, Spain, SL, Steinhart, AH, Stempak, JM, Stronati, L, Sventoraityte, J, Targan, SR, Taylor, KM, Velde, A, Torkvist, L, Tremelling, M, van Sommeren, S, Vasiliauskas, E, Verspaget, HW, Walters, T, Wang, K, Wang, MH, Wei, Z, Whiteman, D, Wijmenga, C, Wilson, DC, Winkelmann, J, Xavier, RJ, Zhang, B, Zhang, CK, Zhang, H, Zhang, W, Zhao, HY, Zhao, ZZ, Momozawa, Y, Dmitrieva, J, Theatre, E, Deffontaine, V, Rahmouni, S, Charloteaux, B, Crins, F, Docampo, E, Elansary, M, Gori, A, Lecut, C, Mariman, R, Mni, M, Oury, C, Altukhov, I, Alexeev, D, Aulchenko, Y, Amininejad, L, Bouma, G, Hoentjen, F, Lowenberg, M, Oldenburg, B, Pierik, Mj, vander Meulen-de Jong, Ae, van der Woude, Cj, Visschedijk, Mc, Lathrop, M, Hugot, Jp, Weersma, Rk, De Vos, M, Franchimont, D, Vermeire, S, Kubo, M, Louis, E, Georges, M, Abraham, C, Achkar, Jp, Ahmad, T, Ananthakrishnan, An, Andersen, V, Anderson, Ca, Andrews, Jm, Annese, V, Aumais, G, Baidoo, L, Baldassano, Rn, Bampton, Pa, Barclay, M, Barrett, Jc, Bayless, Tm, Bethge, J, Bitton, A, Boucher, G, Brand, S, Brandt, B, Brant, Sr, Buning, C, Chew, A, Cho, Jh, Cleynen, I, Cohain, A, Croft, A, Daly, Mj, D'Amato, M, Danese, S, De Jong, D, Denapiene, G, Denson, La, Devaney, Kl, Dewit, O, D'Inca, R, Dubinsky, M, Duerr, Rh, Edwards, C, Ellinghaus, D, Essers, J, Ferguson, Lr, Festen, Ea, Fleshner, P, Florin, T, Franke, A, Fransen, K, Gearry, R, Gieger, C, Glas, J, Goyette, P, Green, T, Griffiths, Am, Guthery, Sl, Hakonarson, H, Halfvarson, J, Hanigan, K, Haritunians, T, Hart, A, Hawkey, C, Hayward, Nk, Hedl, M, Henderson, P, Hu, Xh, Huang, Hl, Hui, Ky, Imielinski, M, Ippoliti, A, Jonaitis, L, Jostins, L, Karlsen, Th, Kennedy, Na, Khan, Ma, Kiudelis, G, Krishnaprasad, K, Kugathasan, S, Kupcinskas, L, Latiano, A, Laukens, D, Lawrance, Ic, Lee, Jc, Lees, Cw, Leja, M, Van Limbergen, J, Lionetti, P, Liu, Jz, Mahy, G, Mansfield, J, Massey, D, Mathew, Cg, Mcgovern, Dpb, Milgrom, R, Mitrovic, M, Montgomery, Gw, Mowat, C, Newman, W, Ng, A, Ng, Sc, Ng, Sme, Nikolaus, S, Ning, K, Nothen, M, Oikonomou, I, Palmieri, O, Parkes, M, Phillips, A, Ponsioen, Cy, Potocnik, U, Prescott, Nj, Proctor, Dd, Radford-Smith, G, Rahier, Jf, Raychaudhuri, S, Regueiro, M, Rieder, F, Rioux, Jd, Ripke, S, Roberts, R, Russell, Rk, Sanderson, Jd, Sans, M, Satsangi, J, Schadt, Ee, Schreiber, S, Schulte, D, Schumm, Lp, Scott, R, Seielstad, M, Sharma, Y, Silverberg, M, Simms, La, Skieceviciene, J, Spain, Sl, Steinhart, Ah, Stempak, Jm, Stronati, L, Sventoraityte, J, Targan, Sr, Taylor, Km, ter Velde, A, Torkvist, L, Tremelling, M, van Sommeren, S, Vasiliauskas, E, Verspaget, Hw, Walters, T, Wang, K, Wang, Mh, Wei, Z, Whiteman, D, Wijmenga, C, Wilson, Dc, Winkelmann, J, Xavier, Rj, Zhang, B, Zhang, Ck, Zhang, H, Zhang, W, Zhao, Hy, Zhao, Zz, Gastroenterology & Hepatology, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, and UCL - (MGD) Service de gastro-entérologie
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Adult ,Male ,Multifactorial Inheritance ,QUANTITATIVE TRAIT LOCUS ,Genotype ,SEQUENCING DATA ,Quantitative Trait Loci ,SUSCEPTIBILITY ,Polymorphism, Single Nucleotide ,Article ,Cohort Studies ,CODING VARIANTS ,Crohn Disease ,80 and over ,Journal Article ,Medicine and Health Sciences ,LOCUS ,Humans ,Genetic Predisposition to Disease ,Polymorphism ,GENOME-WIDE ASSOCIATION ,Genetic Association Studies ,Aged ,Aged, 80 and over ,Science & Technology ,Female ,Gene Expression Profiling ,Inflammatory Bowel Diseases ,Middle Aged ,Sequence Analysis, DNA ,COMPLEX TRAITS ,Biology and Life Sciences ,Single Nucleotide ,DNA ,CROHNS-DISEASE ,Multidisciplinary Sciences ,QUANTITATIVE TRAIT ,RARE VARIANTS ,Science & Technology - Other Topics ,LOW-FREQUENCY ,Sequence Analysis ,INFLAMMATORY-BOWEL-DISEASE - Abstract
GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach., Most of the more than 200 known genetic risk loci for inflammatory bowel disease (IBD) reside in regulatory regions. Here, the authors provide eQTL datasets for six circulating immune cell types and ileal, colonic and rectal biopsies to map regulatory modules and identify potential causative genes for IBD.
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- 2018
6. Vergleich der Hochtontherapie und der TENS Therapie bei chemotherapieinduzierter Polyneuropathie – Projekt HIT-CIPN – Studienprotokoll eines RCT
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Johansson, T, Schaffler-Schaden, D, Herfert, J, Sassmann, R, Gampenrieder, S, Rinnerthaler, G, Lampl, K, Rieder, F, Flamm, M, Greil, R, and Niebauer, J
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Hintergrund: Eine häufige Nebenwirkung vor allem Oxaliplatin- und Taxanbasierter Therapien ist die Neurotoxizität, was zu Dosisreduktion oder gar Abbruch der Therapie führen kann und damit die Prognose dieser PatientInnen beeinflusst. Fragestellung: Klinische Besserung der chemotherapieinduzierten[zum vollständigen Text gelangen Sie über die oben angegebene URL], 53. Kongress für Allgemeinmedizin und Familienmedizin
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- 2019
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7. The Pathogenesis of Extraintestinal Manifestations: Implications for IBD Research, Diagnosis, and Therapy
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Hedin, C.R.H. Vavricka, S.R. Stagg, A.J. Schoepfer, A. Raine, T. Puig, L. Pleyer, U. Navarini, A. Van Der Meulen-De Jong, A.E. Maul, J. Katsanos, K. Kagramanova, A. Greuter, T. González-Lama, Y. Van Gaalen, F. Ellul, P. Burisch, J. Bettenworth, D. Becker, M.D. Bamias, G. Rieder, F.
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education - Abstract
This article reports on the sixth scientific workshop of the European Crohn's and Colitis Organisation [ECCO] on the pathogenesis of extraintestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. This paper has been drafted by 15 ECCO members and 6 external experts [in rheumatology, dermatology, ophthalmology, and immunology] from 10 European countries and the USA. Within the workshop, contributors formed subgroups to address specific areas. Following a comprehensive literature search, the supporting text was finalized under the leadership of the heads of the working groups before being integrated by the group consensus leaders. Copyright © 2018 European Crohn's and Colitis Organisation (ECCO).
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- 2019
8. European Evidence-based Consensus: Inflammatory Bowel Disease and Malignancies
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Annese, Vito, Beaugerie, Laurent, Egan, Laurence, Biancone, Livia, Bolling, Claus, Brandts, Christian, Dierickx, Daan, Dummer, Reinhard, Fiorino, Gionata, Gornet, Jean Marc, Higgins, Peter, Katsanos, Konstantinos H., Nissen, Loes, Pellino, Gianluca, Rogler, Gerhard, Scaldaferri, Franco, Szymanska, Edyta, Eliakim, Rami, Bossuyt, P., Bogut, A., Krznaric, Z., Mijandrusic Sincic, B., Bortlik, M., Douda, T., Knudsen, T., Manninen, P., Nieminen, U., Kucharzik, T., Siegmund, B., Koutroubakis, I., Epameinondas, T., Lakatos, P., Waterman, M., Kohn, A., Goll, Null, Kierkus, J., Zagorowicz, E., Diculescu, M. M., Tarabar, D., Drobne, D., Gisbert, J., Strid, H., Pierik, M., Celik, A. F., Irving, P., Marshall, J., Riis, L., Amiot, A., Mantzaris, G., Sinagra, E., Sampietro, G., D'Incà, R., De Ridder, L., Nunesl, P. B., Marin Jimenez, I., Ramirez, V. H., Juillerat, P., Claridge, A., Macdonald, J., Rieder, F., SELVAGGI, Francesco, University of Zurich, Annese, Vito, Bossuyt, Peter, Beaugerie, Laurent, Egan, Laurence, Biancone, Livia, Bolling, Clau, Brandts, Christian, Dierickx, Daan, Dummer, Reinhard, Fiorino, Gionata, Gornet, Jean Marc, Higgins, Peter, Katsanos, Konstantinos H., Nissen, Loe, Pellino, Gianluca, Rogler, Gerhard, Scaldaferri, Franco, Szymanska, Edyta, Eliakim, Rami, Bossuyt, P., Bogut, A., Krznaric, Z., Mijandrusic Sincic, B., Bortlik, M., Douda, T., Knudsen, T., Manninen, P., Nieminen, U., Kucharzik, T., Siegmund, B., Koutroubakis, I., Epameinondas, T., Lakatos, P., Waterman, M., Kohn, A., Goll, Null, Kierkus, J., Zagorowicz, E., Diculescu, M. M., Tarabar, D., Drobne, D., Gisbert, J., Strid, H., Pierik, M., Celik, A. F., Irving, P., Marshall, J., Riis, L., Amiot, A., Mantzaris, G., Sinagra, E., Selvaggi, Francesco, Sampietro, G., D'Incà, R., De Ridder, L., Nunesl, P. B., Marin Jimenez, I., Ramirez, V. H., Juillerat, P., Claridge, A., Macdonald, J., and Rieder, F.
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medicine.medical_specialty ,Evidence-based practice ,Prognosi ,Alternative medicine ,MEDLINE ,610 Medicine & health ,Malignancy ,Inflammatory bowel disease ,Risk Factors ,Neoplasms ,medicine ,Humans ,2715 Gastroenterology ,Settore MED/12 - Gastroenterologia ,Evidence-Based Medicine ,business.industry ,Risk Factor ,Medicine (all) ,Inflammatory Bowel Disease ,Gastroenterology ,10177 Dermatology Clinic ,Cancer ,General Medicine ,Evidence-based medicine ,Inflammatory Bowel Diseases ,Prognosis ,medicine.disease ,Ulcerative colitis ,Europe ,10219 Clinic for Gastroenterology and Hepatology ,Family medicine ,Immunology ,Neoplasm ,business ,Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5] ,Human - Abstract
The global prevalence of cancer is increasing, largely as more patients are living into old age. Therefore, gastroenterologists caring for patients with inflammatory bowel disease [IBD] increasingly are managing patients with cancer, or a previous history of cancer. This often requires joint management with the patient’s oncologist, enabling case-by-case decision-making based on the characteristics and expected evolution of the index cancer. Previously, no European guidelines existed describing the impact of IBD on malignancy. For this reason, the European Crohn’s and Colitis Organisation [ECCO] Guidelines Committee [GuiCom] decided to elaborate a set of Consensus Statements on optimal risk/benefit strategies for treating IBD patients with cancer or a history of cancer. The development of clinical practice guidelines is expensive and time consuming, and it is the Committee’s hope that these statements will facilitate and accelerate future efforts to elaborate formal guidelines, providing useful information on areas for which evidence is lacking and where controlled studies are needed. The strategy used to produce the Consensus Statements involved five steps: 1. Two members of Guicom [VA and RE] identified four main topics that needed to be addressed: a] IBD and solid tumours; b] IBD and skin and haematological malignancies; c] malignancy related to therapy: risk and prevention; and d] management of IBD patients with a history of malignancy. During 2014, calls for participation in the drafting of consensus statements were issued to ECCO members, and selected oncologists known for their expertise and active research in the field were invited to join the Consensus. Participants were selected by the Committee, and four working groups were created, each composed of a chairperson [LE, RE, LB, and VA], two ECCO members including young members [Y-ECCO], and one or two experienced oncologists. The chairmen and their groups elaborated relevant questions on topics dealing with current practice and/or areas …
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- 2015
9. IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
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Momozawa, Y., Dmitrieva, J., Theatre, E., Deffontaine, V., Rahmouni, S., Charloteaux, B., Crins, F., Docampo, E., Elansary, M., Gori, A.S., Lecut, C., Mariman, R., Mni, M., Oury, C., Altukhov, I., Alexeev, D., Aulchenko, Y., Amininejad, L., Bouma, G., Hoentjen, F., Lowenberg, M., Oldenburg, B., Pierik, M.J., vander Meulen-de Jong, A.E., Woude, C.J. van der, Visschedijk, M.C., Lathrop, M., Hugot, J.P., Weersma, R.K., Vos, M. de, Franchimont, D., Vermeire, S., Kubo, M., Louis, E., Georges, M., Abraham, C., Achkar, J.P., Ahmad, T., Ananthakrishnan, A.N., Andersen, V., Anderson, C.A., Andrews, J.M., Annese, V., Aumais, G., Baidoo, L., Baldassano, R.N., Bampton, P.A., Barclay, M., Barrett, J.C., Bayless, T.M., Bethge, J., Bitton, A., Boucher, G., Brand, S., Brandt, B., Brant, S.R., Buning, C., Chew, A., Cho, J.H., Cleynen, I., Cohain, A., Croft, A., Daly, M.J., D'Amato, M., Danese, S., Jong, D. de, Denapiene, G., Denson, L.A., Devaney, K.L., Dewit, O., D'Inca, R., Dubinsky, M., Duerr, R.H., Edwards, C., Ellinghaus, D., Essers, J., Ferguson, L.R., Festen, E.A., Fleshner, P., Florin, T., Franke, A., Fransen, K., Gearry, R., Gieger, C., Glas, J., Goyette, P., Green, T., Griffiths, A.M., Guthery, S.L., Hakonarson, H., Halfvarson, J., Hanigan, K., Haritunians, T., Hart, A., Hawkey, C., Hayward, N.K., Hedl, M., Henderson, P., Hu, X.H., Huang, H.L., Hui, K.Y., Imielinski, M., Ippoliti, A., Jonaitis, L., Jostins, L., Karlsen, T.H., Kennedy, N.A., Khan, M.A., Kiudelis, G., Krishnaprasad, K., Kugathasan, S., Kupcinskas, L., Latiano, A., Laukens, D., Lawrance, I.C., Lee, J.C., Lees, C.W., Leja, M., Limbergen, J. van, Lionetti, P., Liu, J.Z., Mahy, G., Mansfield, J., Massey, D., Mathew, C.G., McGovern, D.P.B., Milgrom, R., Mitrovic, M., Montgomery, G.W., Mowat, C., Newman, W., Ng, A., Ng, S.C., Ng, S.M.E., Nikolaus, S., Ning, K., Nothen, M., Oikonomou, I., Palmieri, O., Parkes, M., Phillips, A., Ponsioen, C.Y., Potocnik, U., Prescott, N.J., Proctor, D.D., Radford-Smith, G., Rahier, J.F., Raychaudhuri, S., Regueiro, M., Rieder, F., Rioux, J.D., Ripke, S., Roberts, R., Russell, R.K., Sanderson, J.D., Sans, M., Satsangi, J., Schadt, E.E., Schreiber, S., Schulte, D., Schumm, L.P., Scott, R., Seielstad, M., Sharma, Y., Silverberg, M.S., Simms, L.A., Skieceviciene, J., Spain, S.L., Steinhart, A.H., Stempak, J.M., Stronati, L., Sventoraityte, J., Targan, S.R., Taylor, K.M., Velde, A. ter, Torkvist, L., Tremelling, M., Sommeren, S. van, Vasiliauskas, E., Verspaget, H.W., Walters, T., Wang, K., Wang, M.H., Wei, Z., Whiteman, D., Wijmenga, C., Wilson, D.C., Winkelmann, J., Xavier, R.J., Zhang, B., Zhang, C.K., Zhang, H., Zhang, W., Zhao, H.Y., Zhao, Z.Z., and Int IBD Genetics Consortium
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- 2018
10. Influence of carbonate and gluconate on the Eu(III) and Cm(III) sorption onto clay minerals
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Rieder, F., Rabung, Th., Geckeis, H., and Schäfer, Th.
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Technology ,ddc:600 - Published
- 2017
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11. An expert consensus to standardise definitions, diagnosis and treatment targets for anti‐fibrotic stricture therapies in Crohn's disease
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Rieder, F., primary, Bettenworth, D., additional, Ma, C., additional, Parker, C. E., additional, Williamson, L. A., additional, Nelson, S. A., additional, van Assche, G., additional, Di Sabatino, A., additional, Bouhnik, Y., additional, Stidham, R. W., additional, Dignass, A., additional, Rogler, G., additional, Taylor, S. A., additional, Stoker, J., additional, Rimola, J., additional, Baker, M. E., additional, Fletcher, J. G., additional, Panes, J., additional, Sandborn, W. J., additional, Feagan, B. G., additional, and Jairath, V., additional
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- 2018
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12. Fibrosis in ulcerative colitis is directly linked to severity and chronicity of mucosal inflammation
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Gordon, I. O., primary, Agrawal, N., additional, Willis, E., additional, Goldblum, J. R., additional, Lopez, R., additional, Allende, D., additional, Liu, X., additional, Patil, D. Y., additional, Yerian, L., additional, El-Khider, F., additional, Fiocchi, C., additional, and Rieder, F., additional
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- 2018
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13. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes:a genetic association study
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Cleynen, Isabelle, Boucher, Gabrielle, Jostins, Luke, Schumm, L. Philip, Zeissig, Sebastian, Ahmad, Tariq, Andersen, Vibeke, Andrews, Jane M., Annese, Vito, Brand, Stephan, Brant, Steven R., Cho, Judy H., Daly, Mark J., Dubinsky, Marla, Duerr, Richard H., Ferguson, Lynnette R., Franke, Andre, Gearry, Richard B., Goyette, Philippe, Hakonarson, Hakon, Halfvarson, Jonas, Hov, Johannes R., Huang, Hailang, Kennedy, Nicholas A., Kupcinskas, Limas, Lawrance, Ian C., Lee, James C., Satsangi, Jack, Schreiber, Stephan, Théâtre, Emilie, Van Der Meulen De Jong, Andrea E, Weersma, Rinse K., Wilson, David C., Parkes, Miles, Vermeire, Severine, Rioux, John D., Mansfield, John, Silverberg, Mark S., Radford Smith, Graham, Mcgovern, Dermot P. B., Barrett, Jeffrey C., Lees, Charlie W, Abraham, C, Achkar, Jp, Ahmad, T, Amininejad, L, Ananthakrishnan, An, Andersen, V, Anderson, Ca, Andrews, Jm, Annese, V, Aumais, G, Baidoo, L, Baldassano, Rn, Bampton, Pa, Barclay, M, Barrett, Jc, Bayless, Tm, Bethge, J, Bis, Jc, Bitton, A, Boucher, G, Brand, S, Brandt, B, Brant, Sr, Büning, C, Chew, A, Cho, Jh, Cleynen, I, Cohain, A, Croft, A, Daly, Mj, D'Amato, M, Danese, S, De Jong, D, De Vos, M, Denapiene, G, Denson, La, Devaney, K, Dewit, O, D'Inca, R, Dubinsky, M, Duerr, Rh, Edwards, C, Ellinghaus, D, Essers, J, Ferguson, Lr, Festen, Ea, Fleshner, P, Florin, T, Franchimont, D, Franke, A, Fransen, K, Gearry, R, Georges, M, Gieger, C, Glas, J, Goyette, P, Green, T, Griffiths, Am, Guthery, Sl, Hakonarson, H, Halfvarson, J, Hanigan, K, Haritunians, T, Hart, A, Hawkey, C, Hayward, Nk, Hedl, M, Henderson, P, Hu, X, Huang, H, Hui, Ky, Imielinski, M, Ippoliti, A, Jonaitis, L, Jostins, L, Karlsen, Th, Kennedy, Na, Khan, Ma, Kiudelis, G, Krishnaprasad, K, Kugathasan, S, Kupcinskas, L, Latiano, A, Laukens, D, Lawrance, Ic, Lee, Jc, Lees, Cw, Leja, M, Van Limbergen, J, Lionetti, P, Liu, Jz, Louis, E, Mahy, G, Mansfield, J, Massey, D, Mathew, Cg, Mcgovern, Dp, Milgrom, R, Mitrovic, M, Montgomery, Gw, Mowat, C, Newman, W, Ng, A, Ng, Sc, Ng, Sm, Nikolaus, S, Ning, K, Nöthen, M, Oikonomou, I, Palmieri, O, Parkes, M, Phillips, A, Ponsioen, Cy, Potocnik, U, Prescott, Nj, Proctor, Dd, Radford Smith, G, Rahier, Jf, Raychaudhuri, S, Regueiro, M, Rieder, F, Rioux, Jd, Ripke, S, Roberts, R, Russell, Rk, Sanderson, Jd, Sans, M, Satsangi, J, Schadt, Ee, Schreiber, S, Schumm, Lp, Scott, R, Seielstad, M, Sharma, Y, Silverberg, Ms, Simms, La, Skieceviciene, J, Spain, Sl, Steinhart, A, Stempak, Jm, Stronati, Laura, Sventoraityte, J, Targan, Sr, Taylor, Km, ter Velde, A, Theatre, E, Torkvist, L, Tremelling, M, van der Meulen, A, van Sommeren, S, Vasiliauskas, E, Vermeire, S, Verspaget, Hw, Walters, T, Wang, K, Wang, Mh, Weersma, Rk, Wei, Z, Whiteman, D, Wijmenga, C, Wilson, Dc, Winkelmann, J, Xavier, Rj, Zeissig, S, Zhang, B, Zhang, Ck, Zhang, H, Zhang, W, Zhao, H, Zhao, Zz, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (MGD) Service de gastro-entérologie, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
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Male ,0301 basic medicine ,CLINICAL-COURSE ,Nod2 Signaling Adaptor Protein ,Disease ,SUSCEPTIBILITY ,Inflammatory bowel disease ,Major Histocompatibility Complex ,0302 clinical medicine ,Crohn Disease ,Maintenance therapy ,NOD2 ,Medicine and Health Sciences ,POPULATION ,Immunoassay ,RISK ,Medicine(all) ,education.field_of_study ,Crohn's disease ,Hepatocyte Growth Factor ,Medicine (all) ,INDUCTION ,Articles ,General Medicine ,PRIMARY SCLEROSING CHOLANGITIS ,Ulcerative colitis ,3. Good health ,Phenotype ,Female ,030211 gastroenterology & hepatology ,Adult ,medicine.medical_specialty ,MAINTENANCE THERAPY ,Genotype ,Population ,Polymorphism, Single Nucleotide ,Risk Assessment ,CLASSIFICATION ,Primary sclerosing cholangitis ,Young Adult ,03 medical and health sciences ,inflammatory bowel disease ,Proto-Oncogene Proteins ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,education ,Alleles ,Genetic Association Studies ,business.industry ,medicine.disease ,digestive system diseases ,030104 developmental biology ,Immunology ,Colitis, Ulcerative ,business ,FOLLOW-UP ,HLA-DRB1 Chains ,INFLAMMATORY-BOWEL-DISEASE - Abstract
Background: Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases.Methods: This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile.Findings: After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease subphenotype (p=1·65 × 10−78), even after exclusion of NOD2, MHC, and 3p21 (p=9·23 × 10−18). Predictive models based on the genetic risk score strongly distinguished colonic from ileal Crohn's disease. Our genetic risk score could also identify a small number of patients with discrepant genetic risk profiles who were significantly more likely to have a revised diagnosis after follow-up (p=6·8 × 10−4).Interpretation: Our data support a continuum of disorders within inflammatory bowel disease, much better explained by three groups (ileal Crohn's disease, colonic Crohn's disease, and ulcerative colitis) than by Crohn's disease and ulcerative colitis as currently defined. Disease location is an intrinsic aspect of a patient's disease, in part genetically determined, and the major driver to changes in disease behaviour over time.Funding: International Inflammatory Bowel Disease Genetics Consortium members funding sources (see Acknowledgments for full list).
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- 2016
14. PLATELET ACTIVATING FACTOR AND DISTINCT CHEMOKINES ARE ELEVATED IN MUCOSAL BIOPSIES OF EROSIVE COMPARED TO NON-EROSIVE REFLUX DISEASE PATIENTS AND CONTROLS
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Altomare, A., Ma, J., Guarino, M.P.L., Cheng, L., Rieder, F., Ribolsi, M., Fiocchi, C., Biancani, P., Harnett, K., and Cicala, M.
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Adult ,Male ,Biopsy ,Enzyme-Linked Immunosorbent Assay ,Middle Aged ,Real-Time Polymerase Chain Reaction ,Article ,Gastroesophageal Reflux ,Humans ,Female ,Chemokines ,Platelet Activating Factor ,Esophagitis, Peptic ,Aged - Abstract
A distinction between symptomatic non-erosive reflux disease (NERD) and erosive esophagitis (EE) patients is supported by the presence of inflammatory response in the mucosa of EE patients, leading to a damage of mucosal integrity. To explore the underlying mechanism of this difference, we assessed inflammatory mediators in mucosal biopsies from EE and NERD patients and compared them with controls.Nineteen NERD patients, 15 EE patients, and 16 healthy subjects underwent endoscopy after a 3-week washout from PPI or H(2) antagonists. Biopsies obtained from the distal esophagus were examined by quantitative real-time polymerase chain reaction (qPCR) and multiplex enzyme-linked immunosorbent assay for selected chemokines and lyso-PAF acetyltransferase (LysoPAF-AT), the enzyme responsible for production of platelet-activating factor (PAF).Expression of LysoPAF-AT and multiple chemokines was significantly increased in mucosal biopsies derived from EE patients, when compared with NERD patients and healthy controls. Upregulated chemokines included interleukin 8, eotaxin-1, -2, and -3, macrophage inflammatory protein-1α (MIP-1α), and monocyte chemoattractant protein-1 (MCP-1). LysoPAF-AT and the chemokine profile in NERD patients were comparable with healthy controls.Levels of selected cytokines and Lyso-PAF AT were significantly higher in the esophageal mucosa of EE patients compared with NERD and control patients. This difference may explain the distinct inflammatory response occurring in EE patients' mucosa. In contrast, as no significant differences existed between the levels of all mediators in NERD and control subjects, an inflammatory response does not appear to play a major role in the pathogenesis of the abnormalities found in NERD patients.
- Published
- 2012
15. Review article: breath analysis in inflammatory bowel diseases
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Kurada, S., primary, Alkhouri, N., additional, Fiocchi, C., additional, Dweik, R., additional, and Rieder, F., additional
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- 2014
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16. S13 Inflammation-induced endothelial-to-mesenchymal transition (EndoMT): A novel mechanism of fibrosis in IBD
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Rieder, F., primary, Kessler, S., additional, West, G., additional, Gopalan, B., additional, Stylianou, E., additional, de la Motte, C., additional, and Fiocchi, C., additional
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- 2010
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17. S23 Induction of angiogenesis by distinct Nod-like (NLR) and Toll-like (TLR) receptors: Linking innate immunity to bacteria and angiogenesis in IBD
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Schirbel, A., primary, Rieder, F., additional, Scaldaferri, F., additional, Phillips, M., additional, West, G., additional, and Fiocchi, C., additional
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- 2010
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18. HAPPIER.
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RIEDER, F. A.
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SERIAL publications ,READERS - Abstract
A letter to the editor is presented about the periodical being viciously reactionary and undemocratic.
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- 1941
19. Neutralization of IL-18 exerts anti-inflammatory activity in experimental colitis in mice
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Siegmund, B., Fantuzzi, G., Rieder, F., Gamboni-Robertson, F., Eigier, A., Endres, S., and Dinarello, C.A.
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- 2001
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20. In vivo efficacy of the specific type 4 phosphodiesterase inhibitor mesopram in DSS-induced murine colitis
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Loher, F., Schmall, K., Rieder, F., Bauer, C., Siegmund, B., Lehr, H.A., Endres, S., and Eigler, A.
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- 2001
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21. Treatments for Crohn’s Disease–Associated Bowel Damage: A Systematic Review
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Edouard Louis, Dominik Bettenworth, Silvia Speca, Pierre Desreumaux, Silvio Danese, Benjamin Pariente, Marie-Alice Meuwis, Florian Rieder, Shurong Hu, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Pariente, B, Hu, Sr, Bettenworth, D, Speca, S, Desreumaux, P, Meuwis, Ma, Danese, S, Rieder, F, and Louis, E
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medicine.medical_specialty ,Crohn's disease ,Hepatology ,business.industry ,[SDV]Life Sciences [q-bio] ,Mesenchymal stem cell ,Gastroenterology ,Tissue inhibitor of metalloproteinase ,medicine.disease ,Ulcerative colitis ,Inflammatory bowel disease ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,Hepatocyte growth factor ,Stem cell ,business ,medicine.drug - Abstract
Background & Aims Despite significant advances in the treatment of Crohn's disease (CD), most patients still develop stricturing or penetrating complications that require surgical resections. We performed a systematic review of mechanisms and potential treatments for tissue damage lesions in CD patients. Methods We searched the PubMed, MBASE, and Cochrane databases from January 1960 to July 2017 for full-length articles on CD, fibrosis, damage lesions, mesenchymal stem cells, and/or treatment. We also searched published conference abstracts and performed manual searches of all reference lists of relevant articles. Results Mechanisms of intestinal damage in patients with CD include fibroblast proliferation and migration, activation of stellate cells, recruitment of intestinal or extra-intestinal fibroblast, and cell trans-differentiation. An altered balance of metalloproteinases and tissue inhibitors of metalloproteinases might contribute to fistula formation. Treatment approaches that reduce excessive transforming growth factor beta (TGFB) activation might be effective in treating established intestinal damage. Stem cell therapies have been effective in tissue damage lesions in CD. Particularly, randomized controlled trials have shown local injections of mesenchymal stem cells to heal perianal fistulas. Conclusion In a systematic review of mechanisms and treatments of bowel wall damage in patients with CD, we found a need to test drugs that reduce TGFB and increase healing of transmural damage lesions and to pursue research on local injection of mesenchymal stem cells.
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- 2019
22. An expert consensus to standardize definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Crohn’s disease
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Ryan W. Stidham, G. Van Assche, Gerhard Rogler, Florian Rieder, Dominik Bettenworth, Christopher Ma, A. Di Sabatino, Stuart A. Taylor, L. A. Williamson, Brian G. Feagan, Mark E. Baker, Joel G. Fletcher, Jaap Stoker, Jordi Rimola, Vipul Jairath, Claire E Parker, Yoram Bouhnik, Julià Panés, Sigrid Nelson, Axel Dignass, W J Sandborn, University of Zurich, and Rieder, F
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Abdominal pain ,medicine.medical_specialty ,610 Medicine & health ,Inflammatory bowel disease ,Article ,03 medical and health sciences ,0302 clinical medicine ,Colon surgery ,medicine ,2736 Pharmacology (medical) ,2715 Gastroenterology ,Pharmacology (medical) ,Crohn's disease ,Hepatology ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Abdominal distension ,medicine.disease ,Endoscopy ,Clinical trial ,10219 Clinic for Gastroenterology and Hepatology ,030220 oncology & carcinogenesis ,Balloon dilation ,2721 Hepatology ,030211 gastroenterology & hepatology ,Radiology ,medicine.symptom ,business - Abstract
BACKGROUND: Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti‐fibrotic therapies are available; however, several therapies are currently under evaluation. Drug development for the indication of stricturing CD is hampered by a lack of standardised definitions, diagnostic modalities, clinical trial eligibility criteria, endpoints and treatment targets in stricturing CD. AIM: To standardise definitions, diagnosis and treatment targets for anti‐fibrotic stricture therapies in Chron's disease. METHODS: An interdisciplinary expert panel consisting of 15 gastroenterologists and radiologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 109 candidate items derived from systematic review and expert opinion focusing on small intestinal strictures were anonymously rated as inappropriate, uncertain or appropriate. Survey results were discussed as a group before a second and third round of voting. RESULTS: Fibrotic strictures are defined by the combination of luminal narrowing, wall thickening and pre‐stenotic dilation. Definitions of anastomotic (at site of prior intestinal resection with anastomosis) and naive small bowel strictures were similar; however, there was uncertainty regarding wall thickness in anastomotic strictures. Magnetic resonance imaging is considered the optimal technique to define fibrotic strictures and assess response to therapy. Symptomatic strictures are defined by abdominal distension, cramping, dietary restrictions, nausea, vomiting, abdominal pain and post‐prandial abdominal pain. Need for intervention (endoscopic balloon dilation or surgery) within 24‐48 weeks is considered the appropriate endpoint in pharmacological trials. CONCLUSIONS: Consensus criteria for diagnosis and response to therapy in stricturing Crohn's disease should inform both clinical practice and trial design.
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- 2018
23. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 2
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Hannah Gordon, Steve Halligan, Florian Rieder, Gionata Fiorino, Stephan R. Vavricka, Daniel C. Baumgart, Damian Tolan, Pierre Ellul, Torsten Kucharzik, Rami Eliakim, Paula Borralho Nunes, Andreas Sturm, Paulo Gustavo Kotze, Bram Verstockt, Emma Calabrese, Jimmy K. Limdi, Jaap Stoker, Andrea Laghi, Uri Kopylov, Christian Maaser, Jordi Rimola, Dominik Bettenworth, Johan Burisch, Fabiana Castiglione, Vito Annese, Konstantinos Katsanos, Patrick F. van Rheenen, Eduards Krustins, Stuart A. Taylor, Yago González Lama, Sturm, A., Maaser, C., Calabrese, E., Annese, V., Fiorino, G., Kucharzik, T., Vavricka, S. R., Verstockt, B., Van Rheenen, P., Tolan, D., Taylor, S. A., Rimola, J., Rieder, F., Limdi, J. K., Laghi, A., Krustins, E., Kotze, P. G., Kopylov, U., Katsanos, K., Halligan, S., Gordon, H., Lama, Y. G., Ellul, P., Eliakim, R., Castiglione, F., Burisch, J., Nunes, P. B., Bettenworth, D., Baumgart, D. C., Stoker, J., Division 5, Repositório da Universidade de Lisboa, Radiology and Nuclear Medicine, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, and Center for Liver, Digestive and Metabolic Diseases (CLDM)
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Diagnostic Imaging ,medicine.medical_specialty ,European Society of Gastrointestinal and Abdominal Radiology [ESGAR] ,International Cooperation ,MEDLINE ,Inflammatory bowel disease ,Severity of Illness Index ,Endoscopy, Gastrointestinal ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Settore MED/12 ,0302 clinical medicine ,Severity of illness ,medicine ,Humans ,Intensive care medicine ,Irritable bowel syndrome ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,General Medicine ,Guideline ,medicine.disease ,Inflammatory Bowel Diseases ,Endoscopy ,European Crohn’s and Colitis Organisation [ECCO] ,Intestines ,Research Design ,Diagnostic assessment ,030211 gastroenterology & hepatology ,Ultrasonography ,Symptom Assessment ,business - Abstract
Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved, Clinical indexes are useful for standardising disease activity. However, despite widespread use, no score has been validated in clinical practice.
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- 2019
24. Diagnostic delay in inflammatory bowel diseases in a German population.
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Blüthner E, Dehe A, Büning C, Siegmund B, Prager M, Maul J, Krannich A, Preiß J, Wiedenmann B, Rieder F, Khedraki R, Tacke F, Sturm A, and Schirbel A
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- Humans, Female, Male, Adult, Prospective Studies, Middle Aged, Risk Factors, Surveys and Questionnaires statistics & numerical data, Time Factors, Young Adult, Germany epidemiology, Referral and Consultation statistics & numerical data, Aged, Diarrhea diagnosis, Diarrhea etiology, Diarrhea epidemiology, Adolescent, Delayed Diagnosis statistics & numerical data, Crohn Disease diagnosis, Crohn Disease epidemiology, Colitis, Ulcerative diagnosis, Colitis, Ulcerative epidemiology
- Abstract
Background: Early diagnosis is key to prevent bowel damage in inflammatory bowel disease (IBD). Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients exists., Aim: To identify risk factors leading to prolonged diagnostic time in a German IBD cohort., Methods: Between 2012 and 2022, 430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD diagnosis. Total diagnostic time was defined as the time from symptom onset to consulting a physician (patient waiting time) and from first consultation to IBD diagnosis (physician diagnostic time). Univariate and multivariate analyses were performed to identify risk factors for each time period., Results: The total diagnostic time was significantly longer in Crohn's disease (CD) compared to ulcerative colitis (UC) patients (12.0 vs 4.0 mo; P < 0.001), mainly due to increased physician diagnostic time (5.5 vs 1.0 mo; P < 0.001). In a multivariate analysis, the predominant symptoms diarrhea ( P = 0.012) and skin lesions ( P = 0.028) as well as performed gastroscopy ( P = 0.042) were associated with longer physician diagnostic time in CD patients. In UC, fever was correlated ( P = 0.020) with shorter physician diagnostic time, while fatigue ( P = 0.011) and positive family history ( P = 0.046) were correlated with longer physician diagnostic time., Conclusion: We demonstrated that CD patients compared to UC are at risk of long diagnostic delay. Future efforts should focus on shortening the diagnostic delay for a better outcome in these patients., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflicts of interest related to this paper., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2024
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25. Systematic review: Defining, diagnosing and monitoring small bowel strictures in Crohn's disease on intestinal ultrasound.
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Lu C, Rosentreter R, Delisle M, White M, Parker CE, Premji Z, Wilson SR, Baker ME, Bhatnagar G, Begun J, Bruining DH, Bryant R, Christensen B, Feagan BG, Fletcher JG, Jairath V, Knudsen J, Kucharzik T, Maaser C, Maconi G, Novak K, Rimola J, Taylor SA, Wilkens R, and Rieder F
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- Humans, Constriction, Pathologic diagnostic imaging, Constriction, Pathologic pathology, Reproducibility of Results, Intestines pathology, Magnetic Resonance Imaging methods, Crohn Disease diagnosis, Crohn Disease diagnostic imaging, Intestinal Obstruction
- Abstract
Background: Stricturing Crohn's disease (CD) occurs most commonly in the terminal ileum and poses a clinical problem. Cross-sectional imaging modalities such as intestinal ultrasound (IUS), computed tomography enterography (CTE), and magnetic resonance enterography (MRE) allow for assessment of the entire bowel wall and associated peri-enteric findings. Radiologic definitions of strictures have been developed for CTE and MRE; their reliability and responsiveness are being evaluated in index development programs. A comprehensive assessment strategy for strictures using IUS is needed., Aims: To provide a detailed summary of definitions, diagnosis and monitoring of strictures on IUS as well as technical aspects of image acquisition., Methods: We searched four databases up to 6 January 2024. Two-stage screening was done in duplicate. We assessed risk of bias using QUADAS-2., Results: There were 56 studies eligible for inclusion. Definitions for strictures on IUS are heterogeneous, but the overall accuracy for diagnosis of strictures is high. The capability of IUS for characterising inflammation versus fibrosis in strictures is not accurate enough to be used in clinical practice or trials. We summarise definitions for improvement of strictures on IUS, and discuss parameters for image acquisition and standardisation., Conclusions: This systematic review is the first step for a structured program to develop a stricture IUS index for CD., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)
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- 2024
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26. Single-cell isolation from full-thickness human intestinal tissue resections for single-cell RNA sequencing.
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West GA, Zhao S, Nguyen QT, Christensen SM, Gordon IO, Holubar SD, Kravarik KM, Fiocchi C, Mukherjee PK, and Rieder F
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- Humans, Cell Death, Cell Separation, Sequence Analysis, RNA, Erythrocytes, Histological Techniques
- Abstract
Single-cell isolation techniques allow the investigation of physical and functional relationships between individual cells within a complex cell population. Here, we present a protocol for single-cell isolation from full-thickness intestinal tissue resections. We describe steps for pre-processing specimens, isolation of lamina propria and muscular layers, and red blood cell lysis. We then detail fixation of isolated cells and assessment of cell quality. The resulting cell suspension can be subjected to RNA sequencing on the 10× Chromium platform. For complete details on the use and execution of this protocol, please refer to Mukherjee et al.
1 ., Competing Interests: Declaration of interests I.O.G. received funding from UCB, Celgene, Gossamer, and Pliant. S.M.C. and K.M.K. are employees of Pfizer, Inc. and may hold stock equity. C.F. received speaker fees from UCB, Genentech, Sandoz, and Janssen and is a consultant for Athos Therapeutics, Inc. F.R. was a consultant to AbbVie, Adnovate, Agomab, Allergan, Arena, AstraZeneca, Boehringer-Ingelheim, Celgene/BMS, CDISC, Celsius, Cowen, Ferring, Galapagos, Galmed, Genentech, Gilead, Gossamer, Granite, Guidepoint, Helmsley, Horizon Therapeutics, Image Analysis Limited, Index Pharma, Landos, Jannsen, Koutif, Mestag, Metacrine, Mopac, Morphic, Organovo, Origo, Pfizer, Inc., Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Sanofi, Surmodics, Surrozen, Takeda, Techlab, Teva, Theravance, Thetis, UCB, Ysios, and 89bio., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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27. Real-world effectiveness and safety of ustekinumab and vedolizumab in elderly patients with Crohn's disease.
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Garg R, Aggarwal M, Mohammed A, Achkar JP, Lashner B, Philpott J, Cohen B, Qazi T, Rieder F, Regueiro M, and Click B
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- Humans, Aged, Ustekinumab adverse effects, Retrospective Studies, Antibodies, Monoclonal, Humanized adverse effects, Treatment Outcome, Remission Induction, Crohn Disease drug therapy
- Abstract
Studies report favorable efficacy and safety profiles of ustekinumab (UST) and vedolizumab (VDZ) in Crohn's disease (CD), but effectiveness and safety data in elderly patients with CD is lacking. We retrospectively analyzed 78 elderly patients (39 each UST and VDZ) and found that patients on UST and VDZ experienced similar rates of clinical response, remission and mucosal healing despite high proportion of prior biologic exposure. Both UST and VDZ appear to be effective and safe in this at-risk CD population. Further large studies are needed to validate our findings., (© 2023. Indian Society of Gastroenterology.)
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- 2023
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28. MFGE8 links absorption of dietary fatty acids with catabolism of enterocyte lipid stores through HNF4γ-dependent transcription of CES enzymes.
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Datta R, Gholampour MA, Yang CD, Volk R, Lin S, Podolsky MJ, Arnold T, Rieder F, Zaro BW, Verzi M, Lehner R, Abumrad N, Lizama CO, and Atabai K
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- Animals, Mice, Antigens, Surface metabolism, Fatty Acids metabolism, Hydrolases metabolism, Lipid Droplets metabolism, Lipid Metabolism, Milk Proteins metabolism, Transcription Factors metabolism, Triglycerides metabolism, Dietary Fats metabolism, Enterocytes metabolism
- Abstract
Enterocytes modulate the extent of postprandial lipemia by storing dietary fats in cytoplasmic lipid droplets (cLDs). We have previously shown that the integrin ligand MFGE8 links absorption of dietary fats with activation of triglyceride (TG) hydrolases that catabolize cLDs for chylomicron production. Here, we identify CES1D as the key hydrolase downstream of the MFGE8-αvβ5 integrin pathway that regulates catabolism of diet-derived cLDs. Mfge8 knockout (KO) enterocytes have reduced CES1D transcript and protein levels and reduced protein levels of the transcription factor HNF4γ. Both Ces1d and Hnf4γ KO mice have decreased enterocyte TG hydrolase activity coupled with retention of TG in cLDs. Mechanistically, MFGE8-dependent fatty acid uptake through CD36 stabilizes HNF4γ protein level; HNF4γ then increases Ces1d transcription. Our work identifies a regulatory network that regulates the severity of postprandial lipemia by linking dietary fat absorption with protein stabilization of a transcription factor that increases expression of hydrolases responsible for catabolizing diet-derived cLDs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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29. Nutritional interventions in adult fibrostenotic Crohn's disease: A systematic review.
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Cooper JL, Rosentreter RE, Filyk A, Premji ZA, Shen H, Ingram R, Kaplan GG, Ma C, Novak K, Panaccione R, Seow CH, Rieder F, Raman M, and Lu C
- Abstract
Background: Management of Crohn's disease (CD) using dietary interventions has become an area of increased research interest. There is a lack of specific research exploring if diet and nutrition interventions are beneficial in patients with strictures, as current dietary recommendations in fibrostenotic CD are often based on clinical judgment. The aim of this systematic review was to assess the impact of dietary interventions in fibrostenotic CD on medical and surgical outcomes., Methods: A systematic search of MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO), and Cochrane Central Register of Controlled Trials (Ovid) was conducted. Studies reporting dietary interventions or nutritional factors in fibrostenotic CD were included. Outcomes for studies assessing dietary interventions such as enteral nutrition were evaluated as changes in (1) CD symptoms (CD Activity Index), (2) stricture parameters on diagnostic imaging, and (3) rates of surgical or medical intervention following dietary interventions., Results: Five studies were included in this review. Three studies assessed exclusive enteral nutrition (EEN), one evaluated total parenteral nutrition (TPN), and one studied a liquid diet. All included studies evaluated symptoms as an outcome, while diagnostic imaging parameters and surgical outcomes in the studies were either absent or too heterogeneous to appraise improvement post dietary intervention. Included EEN studies displayed similar efficacy, with approximately 60% of patients having symptom improvement. The included TPN study also reported 75% of patients with symptom improvement, while the liquid diet did not., Conclusion: Exclusive enteral nutrition and total parental nutrition may provide benefit for use as a dietary intervention for fibrostenotic CD. There remains a need for high-quality controlled trials which utilize standardized definitions of strictures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cooper, Rosentreter, Filyk, Premji, Shen, Ingram, Kaplan, Ma, Novak, Panaccione, Seow, Rieder, Raman and Lu.)
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- 2023
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30. Understanding disruption of the gut barrier during inflammation: Should we abandon traditional epithelial cell lines and switch to intestinal organoids?
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Lechuga S, Braga-Neto MB, Naydenov NG, Rieder F, and Ivanov AI
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- Humans, Inflammation, Cell Line, Epithelial Cells, Organoids, Mucositis, Colonic Neoplasms
- Abstract
Disruption of the intestinal epithelial barrier is a hallmark of mucosal inflammation. It increases exposure of the immune system to luminal microbes, triggering a perpetuating inflammatory response. For several decades, the inflammatory stimuli-induced breakdown of the human gut barrier was studied in vitro by using colon cancer derived epithelial cell lines. While providing a wealth of important data, these cell lines do not completely mimic the morphology and function of normal human intestinal epithelial cells (IEC) due to cancer-related chromosomal abnormalities and oncogenic mutations. The development of human intestinal organoids provided a physiologically-relevant experimental platform to study homeostatic regulation and disease-dependent dysfunctions of the intestinal epithelial barrier. There is need to align and integrate the emerging data obtained with intestinal organoids and classical studies that utilized colon cancer cell lines. This review discusses the utilization of human intestinal organoids to dissect the roles and mechanisms of gut barrier disruption during mucosal inflammation. We summarize available data generated with two major types of organoids derived from either intestinal crypts or induced pluripotent stem cells and compare them to the results of earlier studies with conventional cell lines. We identify research areas where the complementary use of colon cancer-derived cell lines and organoids advance our understanding of epithelial barrier dysfunctions in the inflamed gut and identify unique questions that could be addressed only by using the intestinal organoid platforms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lechuga, Braga-Neto, Naydenov, Rieder and Ivanov.)
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- 2023
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31. Crohn's disease related strictures in cross-sectional imaging: More than meets the eye?
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Sleiman J, Chirra P, Gandhi NS, Baker ME, Lu C, Gordon IO, Viswanath SE, and Rieder F
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- Humans, Constriction, Pathologic diagnosis, Constriction, Pathologic etiology, Constriction, Pathologic pathology, Artificial Intelligence, Intestines pathology, Fibrosis, Crohn Disease complications, Crohn Disease diagnosis, Crohn Disease pathology
- Abstract
Strictures in Crohn's disease (CD) are a hallmark of long-standing intestinal damage, brought about by inflammatory and non-inflammatory pathways. Understanding the complex pathophysiology related to inflammatory infiltrates, extracellular matrix deposition, as well as muscular hyperplasia is crucial to produce high-quality scoring indices for assessing CD strictures. In addition, cross-sectional imaging modalities are the primary tool for diagnosis and follow-up of strictures, especially with the initiation of anti-fibrotic therapy clinical trials. This in turn requires such modalities to both diagnose strictures with high accuracy, as well as be able to delineate the impact of each histomorphologic component on the individual stricture. We discuss the current knowledge on cross-sectional imaging modalities used for stricturing CD, with an emphasis on histomorphologic correlates, novel imaging parameters which may improve segregation between inflammatory, muscular, and fibrotic stricture components, as well as a future outlook on the role of artificial intelligence in this field of gastroenterology., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)
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- 2022
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32. Biomarkers for the Evaluation of Pouch Inflammation: A Systematic Review.
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Falloon K, Cohen BL, Ottichilo R, Grove D, Rieder F, and Qazi T
- Abstract
Background: Ileal pouch inflammation is a common problem following ileal pouch-anal anastomosis (IPAA). Despite its prevalence, diagnosis remains multimodal and requires endoscopy. The use of biomarkers in the prediction of and/or association with pouchitis has not been well characterized. We performed a systematic review to summarize the available evidence., Method: A search of Ovid, MEDLINE, Cochrane Library, EMBASE, and Web of Science was conducted. Inclusion criteria included studies evaluating biomarkers for the evaluation and prediction of inflammation in patients with IPAA utilizing pouchoscopy as the gold standard. Exclusion criteria included studies on the role of the microbiome or genetic markers., Results: A total of 28 studies, 5 case-control studies, and 23 observational cohort studies were identified. Fecal biomarkers were assessed in 23 studies, of which fecal calprotectin was the most commonly studied with sensitivities ranging from 57% to 92% and specificities from 19% to 92%. Six studies examined serum biomarkers. None of the serum biomarkers demonstrated a high sensitivity or specificity in association with pouch inflammation. Six studies described the longitudinal assessment of biomarkers. Of these studies, only three reported a predictive role of biomarkers in diagnosing endoscopic inflammation., Conclusions: Biomarkers have emerged as a potential option to improve the management of pouchitis given the relative ease of sampling compared to pouchoscopy. Unfortunately, the evaluated biomarkers have not consistently demonstrated accuracy in predicting inflammation. Moreover, these biomarkers have not been reliably shown to be sensitive or specific in association with endoscopic pouch inflammation to merit their widespread use in clinical practice., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)
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- 2022
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33. Validation of stricture length, duration and obstructive symptoms as predictors for intervention in ileal stricturing Crohn's disease.
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El Ouali S, Baker ME, Lyu R, Fletcher JG, Bruining DH, Holubar SD, Click B, Qazi T, Cohen BL, and Rieder F
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- Humans, Female, Adult, Male, Crohn Disease diagnosis, Crohn Disease surgery
- Abstract
Background: Risk factors for intervention in terminal ileal (TI) stricturing Crohn's disease (CD) are poorly defined. Novel and rigorous definitions for TI strictures recently became available., Objective: We aimed to describe the rates of symptoms or need for endoscopic balloon dilation (EBD) or surgery as well as risk factors of progression in a well-defined stricturing CD cohort., Methods: Consecutive adult patients with non-penetrating stricturing TI CD, as defined by centrally-read magnetic resonance enterography CONSTRICT criteria, were separated into a derivation and validation cohort. Clinical and imaging characteristics were collected following prespecified scoring conventions. Primary outcome was a composite endpoint of EBD or surgery ("intervention"). Multivariable analysis was performed., Results: Eighty-six patients (48.8% female, median age 36 years) met selection criteria, 17.4% had prior EBD, 59.3% previously received biologics and 58.1% of strictures were anastomotic. Median follow-up was 63.4 [95% CI: 57, 68.9] months. In the derivation cohort, at 12 and 48 months, 26% and 45% of patients had intervention, respectively. Multivariable analysis showed obstructive symptoms (Hazard ratio [HR] 1.444; 95% CI 1.126-1.852), stricture duration (HR 0.974; 95% CI, 0.954-0.995) and length (HR 1.039; 95% CI, 1.011-1.069) predicted intervention. The concordance index for split-sample validation was 0.74 and 0.67, respectively. Biologics were not associated with intervention. An online risk calculator was constructed., Conclusion: In patients with TI stricturing CD, 26% and 45% required intervention at 1 and 4 years. Obstructive symptoms, stricture duration and length were independent and validated predictors of the need for intervention. These findings are important for clinical practice and aid in the design of future trials for CD strictures., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)
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- 2022
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34. Whole body vibration for chronic patellar tendinopathy: A randomized equivalence trial.
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Rieder F, Wiesinger HP, Herfert J, Lampl K, Hecht S, Niebauer J, Maffulli N, Kösters A, Müller E, and Seynnes OR
- Abstract
Purpose: Whole body vibration (WBV) triggers anabolic responses in various tissues, including tendons, without requiring high force production. In this waitlist-controlled equivalence trial, we tested its clinical effectiveness as an alternative treatment for patellar tendinopathy against conventional heavy slow resistance training (HSR). Methods: Thirty-nine patients were randomized to either 3 months of WBV training ( n = 13), HSR training ( n = 11), or a waitlist control (WLC) group ( n = 15). In a partly cross-over design, 14 patients of the WLC group were redistributed to one of the two intervention groups (5 in WBV, 9 in HSR). Pre- and post-intervention testing included pain assessments (VAS), functional limitations (VISA-P), knee extension strength and tendon morphological, mechanical and material properties. Follow-up measurements (VAS, VISA-P) were performed in the WBV and HSR groups 6 months after the intervention. Results: Comparisons with the WLC group revealed significant improvements in VISA-P and VAS scores after HSR (41%, p = 003; 54%, p = 0.005) and WBV (22%, p = 0.022; 56%, p = 0.031) training. These improvements continued until follow-up (HSR: 43%, 56%; WBV: 24%, 37%). Pre-post improvements in VAS scores were equivalent between WBV and HSR groups but inconclusive for the VISA-P score and all pre-test to follow up comparisons. The mid-tendon cross-sectional area was significantly reduced after WBV (-5.7%, p = 0.004) and HSR (-3.0%, p = 0.004) training compared to WLC although the equivalence test between interventions was inconclusive. Conclusion: Whole body vibration improved symptoms typically associated with patellar tendinopathy. This type of intervention is as effective as HSR against maximum pain, although equivalence could not be confirmed for other variables. The beneficial responses to WBV and HSR treatments persisted for 6 months after the end of the intervention. Clinical Trial Registration: https://www.drks.de/drks_web/setLocale_EN.do, identifier DRKS00011338., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rieder, Wiesinger, Herfert, Lampl, Hecht, Niebauer, Maffulli, Kösters, Müller and Seynnes.)
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- 2022
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35. Test Characteristics of Cross-sectional Imaging and Concordance With Endoscopy in Postoperative Crohn's Disease.
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Bachour SP, Shah RS, Lyu R, Nakamura T, Shen M, Li T, Dane B, Barnes EL, Rieder F, Cohen B, Qazi T, Lashner B, Achkar JP, Philpott J, Holubar SD, Lightner AL, Regueiro M, Axelrad J, Baker ME, and Click B
- Subjects
- Adult, Colon surgery, Colonoscopy methods, Humans, Ileum surgery, Recurrence, Retrospective Studies, Crohn Disease diagnostic imaging, Crohn Disease surgery
- Abstract
Background & Aims: Postoperative Crohn's disease (CD) surveillance relies on endoscopic monitoring. The role of cross-sectional imaging is less clear. We evaluated the concordance of cross-sectional enterography with endoscopic recurrence and the predictive ability of radiography for future CD postoperative recurrence., Methods: We performed a multi-institution retrospective cohort study of postoperative adult patients with CD who underwent ileocolonoscopy and cross-sectional enterography within 90 days of each other following ileocecal resection. Imaging studies were interpreted by blinded, expert CD radiologists. Patients were categorized by presence of endoscopic postoperative recurrence (E+) (modified Rutgeerts' score ≥i2b) or radiographic disease activity (R+) and grouped by concordance status., Results: A total of 216 patients with CD with paired ileocolonoscopy and imaging were included. A majority (54.2%) exhibited concordance (34.7% E+/R+; 19.4% E-/R-) between studies. The plurality (41.7%; n = 90) were E-/R+ discordant. Imaging was highly sensitive (89.3%), with low specificity (31.8%), in detecting endoscopic postoperative recurrence. Intestinal wall thickening, luminal narrowing, mural hyper-enhancement, and length of disease on imaging were associated with endoscopic recurrence (all P < .01). Radiographic disease severity was associated with increasing Rutgeerts' score (P < .001). E-/R+ patients experienced more rapid subsequent endoscopic recurrence (hazard ratio, 4.16; P = .033) and increased rates of subsequent endoscopic (43.8% vs 22.7%) and surgical recurrence (20% vs 9.5%) than E-/R- patients (median follow-up, 4.5 years)., Conclusions: Cross-sectional imaging is highly sensitive, but poorly specific, in detecting endoscopic disease activity and postoperative recurrence. Advanced radiographic disease correlates with endoscopic severity. Patients with radiographic activity in the absence of endoscopic recurrence may be at increased risk for future recurrence, and closer monitoring should be considered., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)
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- 2022
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36. Editorial: shedding new light on extraintestinal manifestations in inflammatory bowel disease-authors' reply.
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Falloon K, Cohen B, and Rieder F
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- Humans, Inflammatory Bowel Diseases
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- 2022
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37. Letter: the sphingosine 1 phosphate/sphingosine 1 phosphate receptor axis-a unique therapeutic target in inflammatory bowel disease. Authors' reply.
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Wang J, Goren I, and Rieder F
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- Humans, Molecular Targeted Therapy, Signal Transduction drug effects, Sphingosine metabolism, Inflammatory Bowel Diseases drug therapy, Inflammatory Bowel Diseases metabolism, Lysophospholipids metabolism, Sphingosine analogs & derivatives, Sphingosine-1-Phosphate Receptors metabolism
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- 2022
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38. A United States expert consensus to standardise definitions, follow-up, and treatment targets for extra-intestinal manifestations in inflammatory bowel disease.
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Falloon K, Cohen B, Ananthakrishnan AN, Barnes EL, Bhattacharya A, Colombel JF, Cross RK, Driscoll MS, Fernandez AP, Ha C, Herfarth H, Horst S, Hou J, Husni ME, Kroshinsky D, Kuhn KA, Lowder CY, Martin G, Parikh D, Sayed CJ, Schocket L, Siaton BC, Vedak P, Weisman MH, and Rieder F
- Subjects
- Consensus, Follow-Up Studies, Humans, United States epidemiology, Arthritis diagnosis, Arthritis etiology, Erythema Nodosum diagnosis, Erythema Nodosum epidemiology, Erythema Nodosum etiology, Inflammatory Bowel Diseases complications, Inflammatory Bowel Diseases diagnosis, Inflammatory Bowel Diseases drug therapy, Pyoderma Gangrenosum diagnosis, Pyoderma Gangrenosum therapy, Uveitis diagnosis, Uveitis drug therapy, Uveitis etiology
- Abstract
Background and Aims: Extra-intestinal manifestations (EIMs) are a common complication of inflammatory bowel diseases (IBD), affecting up to half of the patients. Despite their high prevalence, information on standardised definitions, diagnostic strategies, and treatment targets is limited., Methods: As a starting point for a national EIM study network, an interdisciplinary expert panel of 12 gastroenterologists, 4 rheumatologists, 3 ophthalmologists, 6 dermatologists, and 4 patient representatives was assembled. Modified Delphi consensus methodology was used. Fifty-four candidate items were derived from the literature review and expert opinion focusing on five major EIMs (erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis) were rated in three voting rounds., Results: For use in a clinical practice setting and as part of the creation of a prospective registry of patients with EIMs, the panel developed definitions for erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis; identified the appropriate and optimal subspecialists to diagnose and manage each; provided methods to monitor disease course; offered guidance regarding monitoring intervals; and defined resolution and recurrence., Conclusions: Consensus criteria for appropriate and optimal means of diagnosing and monitoring five EIMs have been developed as a starting point to inform clinical practice and future trial design. Key findings include straightforward diagnostic criteria, guidance regarding who can appropriately and optimally diagnose each, and monitoring options that include patient and physician-reported outcomes. These findings will be used in a national multicenter study network to optimise the management of EIMs., (© 2022 John Wiley & Sons Ltd.)
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- 2022
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39. Mild neoterminal ileal post-operative recurrence of Crohn's disease conveys higher risk for severe endoscopic disease progression than isolated anastomotic lesions.
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Bachour SP, Shah RS, Lyu R, Rieder F, Qazi T, Lashner B, Achkar JP, Philpott J, Barnes EL, Axelrad J, Holubar SD, Lightner AL, Regueiro M, Cohen BL, and Click BH
- Subjects
- Adult, Colon pathology, Colon surgery, Colonoscopy, Disease Progression, Humans, Ileum pathology, Ileum surgery, Inflammation pathology, Recurrence, Retrospective Studies, Crohn Disease diagnosis, Crohn Disease pathology, Crohn Disease surgery
- Abstract
There are conflicting data assessing the impact of isolated post-operative anastomotic inflammation on future disease progression. The aim of this study was to determine the relative risk of severe disease progression in post-operative Crohn's disease (CD) patients with isolated anastomotic disease., Methods: Retrospective cohort study of adult CD patients undergoing ileocolonic resection between 2009 and 2020. Patients with a post-operative ileocolonoscopy ≤18 months from surgery and ≥1 subsequent ileocolonoscopy were included. Disease activity was assessed using the modified Rutgeerts' score (RS). Primary outcome was severe endoscopic progression, defined as i3 or i4 disease, on immediate subsequent ileocolonoscopy and during entire post-operative follow-up. Secondary outcome was surgical recurrence., Results: One hundred and ninety-nine CD patients had an ileocolonoscopy ≤18 months from surgery, index RS of i0-i2b and ≥1 subsequent ileocolonoscopy. At index ileocolonoscopy, 34.7% had i0 disease, 16.1% i1, 24.6% i2a and 24.6% i2b. On multivariable logistic regression, i2b disease was associated with severe endoscopic progression compared to i0 or i1 (aOR 5.53; P < 0.001) and i2a disease patients (aOR 2.63; P = 0.03). However, i2a disease did not confer increased risk compared to i0 or i1 disease (P = 0.09). Furthermore, i2b patients experienced severe endoscopic progression significantly earlier than i0 or i1 disease (aHR 4.68; P < 0.001), whereas i2a disease did not differ from i0 or i1 disease (P = 0.25). Surgical recurrence was not associated with index RS i0-i2b (P = 0.86)., Conclusion: Post-operative ileal disease recurrence, not isolated anastomotic inflammation, confers increased risk for severe endoscopic disease progression. Location of CD recurrence may impact optimal management strategies., (© 2022 John Wiley & Sons Ltd.)
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- 2022
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40. P-Cadherin Regulates Intestinal Epithelial Cell Migration and Mucosal Repair, but Is Dispensable for Colitis Associated Colon Cancer.
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Naydenov NG, Lechuga S, Zalavadia A, Mukherjee PK, Gordon IO, Skvasik D, Vidovic P, Huang E, Rieder F, and Ivanov AI
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- Animals, Dextran Sulfate, Epithelial Cells metabolism, Humans, Inflammation metabolism, Intestinal Mucosa pathology, Mice, Mice, Knockout, Cadherins metabolism, Colitis chemically induced, Colitis complications, Colitis metabolism, Colitis-Associated Neoplasms, Inflammatory Bowel Diseases metabolism
- Abstract
Recurrent chronic mucosal inflammation, a characteristic of inflammatory bowel diseases (IBD), perturbs the intestinal epithelial homeostasis resulting in formation of mucosal wounds and, in most severe cases, leads to colitis-associated colon cancer (CAC). The altered structure of epithelial cell-cell adhesions is a hallmark of intestinal inflammation contributing to epithelial injury, repair, and tumorigenesis. P-cadherin is an important adhesion protein, poorly expressed in normal intestinal epithelial cells (IEC) but upregulated in inflamed and injured mucosa. The goal of this study was to investigate the roles of P-cadherin in regulating intestinal inflammation and CAC. P-cadherin expression was markedly induced in the colonic epithelium of human IBD patients and CAC tissues. The roles of P-cadherin were investigated in P-cadherin null mice using dextran sulfate sodium (DSS)-induced colitis and an azoxymethane (AOM)/DSS induced CAC. Although P-cadherin knockout did not affect the severity of acute DSS colitis, P-cadherin null mice exhibited faster recovery after colitis. No significant differences in the number of colonic tumors were observed in P-cadherin null and control mice. Consistently, the CRISPR/Cas9-mediated knockout of P-cadherin in human IEC accelerated epithelial wound healing without affecting cell proliferation. The accelerated migration of P-cadherin depleted IEC was driven by activation of Src kinases, Rac1 GTPase and myosin II motors and was accompanied by transcriptional reprogramming of the cells. Our findings highlight P-cadherin as a negative regulator of IEC motility in vitro and mucosal repair in vivo. In contrast, this protein is dispensable for IEC proliferation and CAC development.
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- 2022
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41. Development of antifibrotic therapy for stricturing Crohn's disease: lessons from randomized trials in other fibrotic diseases.
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Lin SN, Mao R, Qian C, Bettenworth D, Wang J, Li J, Bruining DH, Jairath V, Feagan BG, Chen MH, and Rieder F
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- Constriction, Pathologic diagnosis, Crohn Disease diagnosis, Fibrosis drug therapy, Humans, Inflammation pathology, Intestines drug effects, Intestines pathology, Constriction, Pathologic drug therapy, Crohn Disease drug therapy, Inflammation drug therapy, Randomized Controlled Trials as Topic
- Abstract
Intestinal fibrosis is considered an inevitable complication of Crohn's disease (CD) that results in symptoms of obstruction and stricture formation. Endoscopic or surgical treatment is required to treat the majority of patients. Progress in the management of stricturing CD is hampered by the lack of effective antifibrotic therapy; however, this situation is likely to change because of recent advances in other fibrotic diseases of the lung, liver, and skin. In this review, we summarize data from randomized controlled trials (RCTs) of antifibrotic therapies in these conditions. Multiple compounds have been tested for antifibrotic effects in other organs. According to their mechanisms, they were categorized into growth factor modulators, inflammation modulators, 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, intracellular enzymes and kinases, renin-angiotensin system (RAS) modulators, and others. From our review of the results from the clinical trials and discussion of their implications in the gastrointestinal tract, we have identified several molecular candidates that could serve as potential therapies for intestinal fibrosis in CD.
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- 2022
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42. The Future of Precision Medicine to Predict Outcomes and Control Tissue Remodeling in Inflammatory Bowel Disease.
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Lamb CA, Saifuddin A, Powell N, and Rieder F
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- Biomarkers, Humans, Precision Medicine methods, Systems Biology methods, Colitis, Inflammatory Bowel Diseases diagnosis, Inflammatory Bowel Diseases genetics, Inflammatory Bowel Diseases therapy
- Abstract
Inflammatory bowel disease is characterized by significant interindividual heterogeneity. With a wider selection of pharmacologic and nonpharmacologic interventions available and in advanced developmental stages, a priority for the coming decade is to determine accurate methods of predicting treatment response and disease course. Precision medicine strategies will allow tailoring of preventative and therapeutic decisions to individual patient needs. In this review, we consider the future of precision medicine in inflammatory bowel disease. We discuss the critical need to extend from research focused on short-term symptomatic response to integrative multi-omic systems biology strategies to identify and validate biomarkers that underpin precision approaches. Crucially, the international community has collective responsibility to provide well-phenotyped and -curated longitudinal datasets for scientific discovery and validation. Research must also study broader aspects of the immune response, including components of the extracellular matrix, to better understand biological pathways initiating and perpetuating tissue fibrosis and longer-term disease complications., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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43. Biomarkers for the Prediction and Diagnosis of Fibrostenosing Crohn's Disease: A Systematic Review.
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Steiner CA, Berinstein JA, Louissaint J, Higgins PDR, Spence JR, Shannon C, Lu C, Stidham RW, Fletcher JG, Bruining DH, Feagan BG, Jairath V, Baker ME, Bettenworth D, and Rieder F
- Subjects
- Biomarkers, Cartilage Oligomeric Matrix Protein, Constriction, Pathologic etiology, Humans, Serine Endopeptidases, Crohn Disease complications, Crohn Disease diagnosis, Crohn Disease pathology, Intestinal Obstruction etiology, MicroRNAs
- Abstract
Background and Aims: Intestinal strictures are a common complication of Crohn's disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring. Herein we provide a comprehensive systematic review of studies assessing biomarkers that may predict or diagnose CD-associated strictures., Methods: We performed a systematic review of PubMed, EMBASE, ISI Web of Science, Cochrane Library, and Scopus to identify citations pertaining to biomarkers of intestinal fibrosis through July 6, 2020, that used a reference standard of full-thickness histopathology or cross-sectional imaging or endoscopy. Studies were categorized based on the type of biomarker they evaluated (serum, genetic, histopathologic, or fecal)., Results: Thirty-five distinct biomarkers from 3 major groups were identified: serum (20 markers), genetic (9 markers), and histopathology (6 markers). Promising markers include cartilage oligomeric matrix protein, hepatocyte growth factor activator, and lower levels of microRNA-19-3p (area under the curves were 0.805, 0.738, and 0.67, respectively), and multiple anti-flagellin antibodies (A4-Fla2 [odds ratio, 3.41], anti Fla-X [odds ratio, 2.95], and anti-CBir1 [multiple]). Substantial heterogeneity was observed and none of the markers had undergone formal validation. Specific limitations to acceptance of these markers included failure to use a standardized definition of stricturing disease, lack of specificity, and insufficient relevance to the pathogenesis of intestinal strictures or incomplete knowledge regarding their operating properties., Conclusions: There is a lack of well-defined studies on biomarkers of intestinal stricture. Development of reliable and accurate biomarkers of stricture is a research priority. Biomarkers can support the clinical management of CD patients and aid in the stratification and monitoring of patients during clinical trials of future antifibrotic drug candidates., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)
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- 2022
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44. The Origin and Contribution of Cancer-Associated Fibroblasts in Colorectal Carcinogenesis.
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Kobayashi H, Gieniec KA, Lannagan TRM, Wang T, Asai N, Mizutani Y, Iida T, Ando R, Thomas EM, Sakai A, Suzuki N, Ichinose M, Wright JA, Vrbanac L, Ng JQ, Goyne J, Radford G, Lawrence MJ, Sammour T, Hayakawa Y, Klebe S, Shin AE, Asfaha S, Bettington ML, Rieder F, Arpaia N, Danino T, Butler LM, Burt AD, Leedham SJ, Rustgi AK, Mukherjee S, Takahashi M, Wang TC, Enomoto A, Woods SL, and Worthley DL
- Subjects
- Actins genetics, Actins metabolism, Adult, Aged, Aged, 80 and over, Animals, CD146 Antigen genetics, CD146 Antigen metabolism, Carcinogenesis genetics, Carcinogenesis metabolism, Cell Differentiation, Cell Proliferation, Colorectal Neoplasms metabolism, Disease Models, Animal, Female, Humans, Intestinal Mucosa pathology, Ki-67 Antigen metabolism, Male, Mice, Mice, Transgenic, Middle Aged, Organoids pathology, Organoids physiology, Prognosis, Receptors, Leptin genetics, Receptors, Leptin metabolism, Sequence Analysis, RNA, Survival Rate, Tumor Microenvironment, Cancer-Associated Fibroblasts pathology, Cancer-Associated Fibroblasts physiology, Carcinogenesis pathology, Cell Lineage, Colorectal Neoplasms pathology, Mesenchymal Stem Cells physiology
- Abstract
Background & Aims: Cancer-associated fibroblasts (CAFs) play an important role in colorectal cancer (CRC) progression and predict poor prognosis in CRC patients. However, the cellular origins of CAFs remain unknown, making it challenging to therapeutically target these cells. Here, we aimed to identify the origins and contribution of colorectal CAFs associated with poor prognosis., Methods: To elucidate CAF origins, we used a colitis-associated CRC mouse model in 5 different fate-mapping mouse lines with 5-bromodeoxyuridine dosing. RNA sequencing of fluorescence-activated cell sorting-purified CRC CAFs was performed to identify a potential therapeutic target in CAFs. To examine the prognostic significance of the stromal target, CRC patient RNA sequencing data and tissue microarray were used. CRC organoids were injected into the colons of knockout mice to assess the mechanism by which the stromal gene contributes to colorectal tumorigenesis., Results: Our lineage-tracing studies revealed that in CRC, many ACTA2
+ CAFs emerge through proliferation from intestinal pericryptal leptin receptor (Lepr)+ cells. These Lepr-lineage CAFs, in turn, express melanoma cell adhesion molecule (MCAM), a CRC stroma-specific marker that we identified with the use of RNA sequencing. High MCAM expression induced by transforming growth factor β was inversely associated with patient survival in human CRC. In mice, stromal Mcam knockout attenuated orthotopically injected colorectal tumoroid growth and improved survival through decreased tumor-associated macrophage recruitment. Mechanistically, fibroblast MCAM interacted with interleukin-1 receptor 1 to augment nuclear factor κB-IL34/CCL8 signaling that promotes macrophage chemotaxis., Conclusions: In colorectal carcinogenesis, pericryptal Lepr-lineage cells proliferate to generate MCAM+ CAFs that shape the tumor-promoting immune microenvironment. Preventing the expansion/differentiation of Lepr-lineage CAFs or inhibiting MCAM activity could be effective therapeutic approaches for CRC., (Copyright © 2022 AGA Institute. All rights reserved.)- Published
- 2022
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45. Review article: the sphingosine 1 phosphate/sphingosine 1 phosphate receptor axis - a unique therapeutic target in inflammatory bowel disease.
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Wang J, Goren I, Yang B, Lin S, Li J, Elias M, Fiocchi C, and Rieder F
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- Humans, Phosphates therapeutic use, Sphingosine therapeutic use, Sphingosine-1-Phosphate Receptors, United States, Inflammatory Bowel Diseases drug therapy, Sphingosine 1 Phosphate Receptor Modulators therapeutic use
- Abstract
Background: Ozanimod, a high selective sphingosine 1 phosphate (S1P) receptor (S1PR) 1/5 modulator was approved by the Food and Drug Administration for the treatment of adult patients with moderately to severely active ulcerative colitis. Additional S1PR modulators are being tested in clinical development programmes for both ulcerative colitis and Crohn's disease., Aim: To provide an overview of advances in understanding S1PRs biology and summarise preclinical and clinical investigations of S1P receptor modulators in chronic inflammatory disease with special emphasis on inflammatory bowel diseases (IBD)., Methods: We performed a narrative review using PubMed and ClinicalTrials.gov., Results: Through S1PRs, S1P regulates multiple cellular processes, including proliferation, migration, survival, and vascular barrier integrity. The S1PRs function of regulating lymphocyte trafficking is well known, but new functions of S1PRs expand our knowledge of S1PRs biology. Several S1PR modulators are in clinical development for both ulcerative colitis and Crohn's disease and have shown promise in phase II and III studies with ozanimod now being approved for ulcerative colitis., Conclusions: S1P receptor modulators constitute a novel, promising, safe, and convenient strategy for the treatment of IBD., (© 2021 John Wiley & Sons Ltd.)
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- 2022
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46. Patients With Low Drug Levels or Antibodies to a Prior Anti-Tumor Necrosis Factor Are More Likely to Develop Antibodies to a Subsequent Anti-Tumor Necrosis Factor.
- Author
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Vande Casteele N, Abreu MT, Flier S, Papamichael K, Rieder F, Silverberg MS, Khanna R, Okada L, Yang L, Jain A, and Cheifetz AS
- Subjects
- Adalimumab therapeutic use, Autoantibodies, Genome-Wide Association Study, Humans, Infliximab therapeutic use, Drug Monitoring, Inflammatory Bowel Diseases drug therapy, Tumor Necrosis Factor Inhibitors therapeutic use
- Abstract
Therapeutic drug monitoring (TDM) with measurement of serum drug and antidrug antibodies (ADAb) is used widely to confirm therapeutic exposure, rule out immunogenicity, and optimize treatment of biologics in patients with inflammatory bowel diseases.
1 A recent genome-wide association study found the variant HLA-DQA1∗05 to increase the risk of development of antibodies against infliximab (IFX) and adalimumab (ADM) 2-fold, regardless of concomitant immunomodulator use.2 , 3 However, there is currently limited evidence showing whether patients who develop antibodies to 1 anti-tumor necrosis factor (TNF) are prone to develop antibodies to the subsequent anti-TNF. Our aim was to investigate the risk of subsequent antibody development in cases (with ADAb to prior anti-TNF) versus control subjects (without ADAb to prior anti-TNF) using a large cohort of patients with inflammatory bowel diseases who underwent TDM with a drug-tolerant assay., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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- View/download PDF
47. Not Hard to Swallow-Understanding Endothelial-Fibroblast Crosstalk in Eosinophilic Esophagitis.
- Author
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Beveridge CA, Gabbard S, and Rieder F
- Subjects
- Fibroblasts, Humans, Enteritis, Eosinophilic Esophagitis diagnosis, Esophagitis, Gastritis
- Published
- 2022
- Full Text
- View/download PDF
48. Challenges in the Pathophysiology, Diagnosis, and Management of Intestinal Fibrosis in Inflammatory Bowel Disease.
- Author
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D'Haens G, Rieder F, Feagan BG, Higgins PDR, Panés J, Maaser C, Rogler G, Löwenberg M, van der Voort R, Pinzani M, Peyrin-Biroulet L, and Danese S
- Subjects
- Animals, Antifibrotic Agents adverse effects, Biomarkers metabolism, Crohn Disease metabolism, Crohn Disease pathology, Crohn Disease physiopathology, Fibrosis, Humans, Intestinal Obstruction metabolism, Intestinal Obstruction pathology, Intestinal Obstruction physiopathology, Intestines metabolism, Intestines pathology, Intestines physiopathology, Predictive Value of Tests, Risk Factors, Treatment Outcome, Antifibrotic Agents therapeutic use, Biomedical Research, Crohn Disease drug therapy, Gastroenterology, Intestinal Obstruction prevention & control, Intestines drug effects
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- 2022
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49. Elafin Reverses Intestinal Fibrosis by Inhibiting Cathepsin S-Mediated Protease-Activated Receptor 2.
- Author
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Xie Y, Fontenot L, Chupina Estrada A, Nelson B, Wang J, Shih DQ, Ho W, Mattai SA, Rieder F, Jensen DD, Bunnett NW, and Koon HW
- Subjects
- Animals, Cathepsins, Collagen, Constriction, Pathologic metabolism, Constriction, Pathologic pathology, Elafin, Fibrosis, Humans, Intestines pathology, Mice, Peptide Hydrolases, Polymethacrylic Acids, Protease Inhibitors, Proteome, Receptor, PAR-2, Trinitrobenzenesulfonic Acid toxicity, Zinc Finger E-box-Binding Homeobox 1, Crohn Disease pathology, Intestinal Obstruction pathology
- Abstract
Background & Aims: More than half of Crohn's disease patients develop intestinal fibrosis-induced intestinal strictures. Elafin is a human protease inhibitor that is down-regulated in the stricturing intestine of Crohn's disease patients. We investigated the efficacy of elafin in reversing intestinal fibrosis and elucidated its mechanism of action., Methods: We developed a new method to mimic a stricturing Crohn's disease environment and induce fibrogenesis using stricturing Crohn's disease patient-derived serum exosomes to condition fresh human intestinal tissues and primary stricturing Crohn's disease patient-derived intestinal fibroblasts. Three mouse models of intestinal fibrosis, including SAMP1/YitFc mice, Salmonella-infected mice, and trinitrobenzene sulfonic acid-treated mice, were also studied. Elafin-Eudragit FS30D formulation and elafin-overexpressing construct and lentivirus were used., Results: Elafin reversed collagen synthesis in human intestinal tissues and fibroblasts pretreated with Crohn's disease patient-derived serum exosomes. Proteome arrays identified cathepsin S as a novel fibroblast-derived pro-fibrogenic protease. Elafin directly suppressed cathepsin S activity to inhibit protease-activated receptor 2 activity and Zinc finger E-box-binding homeobox 1 expression, leading to reduced collagen expression in intestinal fibroblasts. Elafin overexpression reversed ileal fibrosis in SAMP1/YitFc mice, cecal fibrosis in Salmonella-infected mice, and colonic fibrosis in trinitrobenzene sulfonic acid-treated mice. Cathepsin S, protease-activated receptor 2 agonist, and zinc finger E-box-binding homeobox 1 overexpression abolished the anti-fibrogenic effect of elafin in fibroblasts and all 3 mouse models of intestinal fibrosis. Oral elafin-Eudragit FS30D treatment abolished colonic fibrosis in trinitrobenzene sulfonic acid-treated mice., Conclusions: Elafin suppresses collagen synthesis in intestinal fibroblasts via cathepsin S-dependent protease-activated receptor 2 inhibition and decreases zinc finger E-box-binding homeobox 1 expression. The reduced collagen synthesis leads to the reversal of intestinal fibrosis. Thus, modified elafin may be a therapeutic approach for intestinal fibrosis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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50. Worse outcomes and higher costs of care in fibrostenotic Crohn's disease: a real-world propensity-matched analysis in the USA.
- Author
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Dehghan M, Wong G, Neuberger E, Kin C, Rieder F, and Park KT
- Subjects
- Adolescent, Adult, Hospitalization, Humans, Longitudinal Studies, Steroids therapeutic use, United States epidemiology, Colitis, Ulcerative diagnosis, Crohn Disease complications, Crohn Disease epidemiology, Crohn Disease therapy
- Abstract
Background: Patients with Crohn's disease (CD) may develop fibrostenotic strictures. No currently available therapies prevent or treat fibrostenotic CD (FCD), making this a critical unmet need., Aim: To compare health outcomes and resource utilisation between CD patients with and without fibrostenotic disease., Methods: Patients aged ≥18 years with FCD and non-FCD between 30 October 2015 and 30 September 2018 were identified in the Truven MarketScan Commercial Claims and Encounters Database. We conducted 1:3 nearest neighbour propensity score matching on age, sex, malnutrition, payer type, anti-tumour necrosis factor use, and Charlson Comorbidity Index score. Primary outcomes up to 1 year from the index claim were ≥1 hospitalisation, ≥1 procedure, ≥1 surgery, and steroid dependency (>100 day supply). Associations between FCD diagnosis and outcomes were estimated with a multivariable logistic regression model. This study was exempt from institutional review board approval., Results: Propensity score matching yielded 11 022 patients. Compared with non-FCD, patients with FCD had increased likelihood of hospitalisations (17.1% vs 52.4%; p<0.001), endoscopic procedures (4.4% vs 8.6%; p<0.001), IBD-related surgeries (4.7% vs 9.1%; p<0.001), steroid dependency (10.0% vs 15.7%; p<0.001), and greater mean annual costs per patient ($47 575 vs $77 609; p<0.001). FCD was a significant risk factor for ≥1 hospitalisation (adjusted OR (aOR), 6.1), ≥1 procedure (aOR, 2.1), ≥1 surgery (aOR, 2.0), and steroid dependency (aOR, 1.7)., Conclusions: FCD was associated with higher risk for hospitalisation, procedures, abdominal surgery, and steroid dependency. Patients with FCD had a greater mean annual cost per patient. FCD represents an ongoing unmet medical need., Competing Interests: Competing interests: MD, GW, EN, and KTP were/are employees of Genentech, Inc, and received salary and stock options. MD and GW were no longer employees of Genentech, Inc at the time of manuscript completion. CK has nothing to disclose. FR is consultant to or on the advisory board of Agomab, Allergan, AbbVie, Boehringer Ingelheim, Celgene/BMS, CDISC, Cowen, Genentech, Gilead, Gossamer, Guidepoint, Helmsley Charitable Trust, Index Pharma, Janssen, Koutif, Mestag, Metacrine, Morphic, Origo, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Surrozen, Takeda, TechLab, Theravance, Thetis, and UCB and is funded by NIH, Helmsley Charitable Trust, Crohn’s and Colitis Foundation, UCB, Pliant, BMS, Pfizer, Boehringer Ingelheim, Morphic, and Kenneth Rainin Foundation., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2021
- Full Text
- View/download PDF
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