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Hagiwara SI, Abe N, Hosoi K, Hara T, Ishige T, Shimizu H, Mizuochi T, Kakiuchi T, Kunisaki R, Matsuoka R, Kondou H, Kakuta F, Nakayama Y, Kimura T, Maeyama T, Honma H, Hirano D, Saruta M, Yoshida T, Okayasu I, Etani Y. Utility of a rapid assay for prostaglandin E-major urinary metabolite as a biomarker in pediatric ulcerative colitis. Sci Rep 2023; 13:9898. [PMID: 37336963 DOI: 10.1038/s41598-023-37145-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Accepted: 06/16/2023] [Indexed: 06/21/2023] Open
Abstract
Prostaglandin E-major urinary metabolite (PGE-MUM) is a urinary biomarker reflecting ulcerative colitis (UC) activity. This prospective observational study aimed to evaluate the usefulness of PGE-MUM via rapid chemiluminescent enzyme immunoassay in detecting endoscopic remission (ER) and histologic remission (HR) in pediatric UC (6-16 years) in comparison with fecal calprotectin (FCP). ER and HR were defined as Mayo endoscopic score (MES) of 0 and Matts' histological grades (Matts) of 1 or 2, respectively. A total of 104 UC and 39 functional gastrointestinal disorder (FGID) were analyzed. PGE-MUM levels were significantly higher in the UC group than in the FGID group (P < 0.001). FCP levels were significantly elevated in the group without ER and HR than in the group with ER and HR (P < 0.001 and P = 0.001), whereas PGE-MUM levels were significantly higher in the group without ER compared to the group with ER (P < 0.001). No significant differences were noted in the AUCs for PGE-MUM and FCP in detecting ER and HR. Although PGE-MUM was inferior to FCP for the detection of HR, it might have the potential for application as a biomarker of endoscopic activity in pediatric UC owing to its noninvasive and rapid method.
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Affiliation(s)
- Shin-Ichiro Hagiwara
- Department of Gastroenterology, Nutrition, and Endocrinology, Osaka Women's and Children's Hospital, 840 Murodocho, Izumi, Osaka, 594-1101, Japan.
| | - Naoki Abe
- Division of Infectious Diseases and Immunology, Aichi Children's Health and Medical Center, Aichi, Japan
| | - Kenji Hosoi
- Department of Gastroenterology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - Tomoko Hara
- Department of Gastroenterology and Hepatology, Saitama Children's Medical Center, Saitama, Japan
| | - Takashi Ishige
- Department of Pediatrics, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Hirotaka Shimizu
- Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Tatsuki Mizuochi
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
| | - Toshihiko Kakiuchi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Reiko Kunisaki
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Ryo Matsuoka
- Department of Pediatrics, Fuji City Central Hospital, Fuji, Japan
| | - Hiroki Kondou
- Department of Pediatrics, Kindai University Nara Hospital, Nara, Japan
| | - Fumihiko Kakuta
- Department of General Pediatrics and Gastroenterology, Miyagi Children's Hospital, Sendai, Japan
| | - Yoshiko Nakayama
- Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan
| | - Takeshi Kimura
- Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Takatoshi Maeyama
- Department of Gastroenterology, Nutrition, and Endocrinology, Osaka Women's and Children's Hospital, 840 Murodocho, Izumi, Osaka, 594-1101, Japan
| | - Hitoshi Honma
- Department of Gastroenterology, Nutrition, and Endocrinology, Osaka Women's and Children's Hospital, 840 Murodocho, Izumi, Osaka, 594-1101, Japan
| | - Daishi Hirano
- Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Tsutomu Yoshida
- Division of Molecular Pathology, Department of Comprehensive Medicine, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Kanagawa, Japan
| | - Isao Okayasu
- Kitasato University School of Medicine, Kanagawa, Japan
| | - Yuri Etani
- Department of Gastroenterology, Nutrition, and Endocrinology, Osaka Women's and Children's Hospital, 840 Murodocho, Izumi, Osaka, 594-1101, Japan
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Magro F, Sabino J, Rosini F, Tripathi M, Borralho P, Baldin P, Danese S, Driessen A, Gordon IO, Iacucci M, Noor N, Svrcek M, Peyrin-Biroulet L, Feakins R. ECCO Position on Harmonisation of Crohn's Disease Mucosal Histopathology. J Crohns Colitis 2022; 16:876-883. [PMID: 35022677 DOI: 10.1093/ecco-jcc/jjac006] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 04/05/2022] [Indexed: 02/08/2023]
Abstract
In inflammatory bowel disease [IBD], mucosal healing is a major therapeutic target and a reliable predictor of clinical course. However, endoscopic mucosal healing is not synonymous with histological healing, and the additional benefits of including histological remission as a target are unclear. In Crohn´s disease [CD], there are few studies highlighting the value of histological remission as a therapeutic target. Histological activity can persist in CD patients who are in endoscopic remission, and the absence of histological activity may be associated with lower relapse rates. Therefore, standardisation of procedures to evaluate CD histological activity is desirable. Topics that would benefit from standardisation and harmonisation include biopsy procedures, biopsy processing techniques, the content of histological scores, and the definitions of histological remission, histological response, and histological activity. In line with these needs, the European Crohn's and Colitis Organisation [ECCO] assembled a consensus group with the objective of developing position statements on CD histology based on published evidence and expert consensus. There was agreement that definitions of histological remission should include absence of erosion, ulceration, and mucosal neutrophils; that the absence of neutrophilic inflammation is an appropriate histological target in CD; that CD histological scores, such as the Global Histological Disease Activity Score, lack formal validation; and that histological scoring systems for ulcerative colitis, including the Geboes Score, Robarts Histopathology Index, and Nancy Histological Index, can be used for scoring intestinal biopsies in CD patients.
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Affiliation(s)
- F Magro
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, University of Porto, Porto, Portugal
| | - J Sabino
- Department of Gastroenterology and Hepatology, University Hospitals, KU Leuven, Leuven, Belgium
| | - F Rosini
- Pathology Unit, IRRCCS, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - M Tripathi
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - P Borralho
- Department of Pathology, Hospital Cuf Descobertas, Lisboa and Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - P Baldin
- Department of Pathology, Cliniques Universitaires St-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - S Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milano, Italy
| | - A Driessen
- Department of Pathology, University Hospital Antwerp, University of Antwerp, Edegem, Belgium
| | - I O Gordon
- Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - M Iacucci
- Institute of Translational Medicine, Institute of Immunology and Immunotherapy, NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, UK
| | - N Noor
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust, Cambridge, UK
| | - M Svrcek
- Sorbonne Université, AP-HP, Hôpital Saint-Antoine, Department of Pathology, Paris, France
| | - L Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandoeuvre-Les-Nancy, France
| | - R Feakins
- Department of Cellular Pathology, Royal Free Hospital, London, UK
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Czajkowska A, Guzinska-Ustymowicz K, Pryczynicz A, Lebensztejn D, Daniluk U. Are Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 Useful as Markers in Diagnostic Management of Children with Newly Diagnosed Ulcerative Colitis? J Clin Med 2022; 11:jcm11092655. [PMID: 35566780 PMCID: PMC9103541 DOI: 10.3390/jcm11092655] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 04/28/2022] [Accepted: 05/06/2022] [Indexed: 02/06/2023] Open
Abstract
Matrix Metaloproteinase-9 (MMP-9) and Tissue Inhibitor of Metaloproteinase-1 (TIMP-1), enzymes involved in tissue remodelling, have been previously reported to be overexpressed in the colonic mucosa of patients with Ulcerative colitis (UC). The aim of this study was to determine the relation of MMP-9 and TIMP-1 with UC phenotypes, the disease activity index and routinely tested inflammatory markers in newly diagnosed paediatric patients. The study group comprised 35 children diagnosed with UC and 20 control groups. Serum and faecal concentrations of MMP-9 and TIMP-1 were estimated using enzyme-like immunosorbent assay kits and correlated to the disease activity index (Paediatric Ulcerative Colitis Activity Index, PUCAI), UC phenotype (Paris Classification), inflammatory markers and endoscopic score (Mayo score). Children with UC presented with significantly higher serum and faecal concentrations of studied markers compared to the control group. Both serums, MMP-9 and TIMP-1, were higher in children with more extended and severe lesions in the colon. Furthermore, serum MMP-9 correlated with the Mayo score, Paris classification and C-reactive protein (CRP) levels. Serum TIMP-1 showed correlation with PUCAI, Paris Classification, CRP levels and the erythrocyte sedimentation rate. Serum and faecal levels of MMP-9 and TIMP-1 are useful in discriminating UC patients and non-invasive assessments of disease phenotypes. It seemed that simultaneous measurement of these proteins in combination with other common markers of inflammation could be applied in clinical practice.
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Affiliation(s)
- Aleksandra Czajkowska
- Department of Pediatrics, Gastroenterology, Hepatology, Nutrition and Allergology, Medical University of Bialystok, 17 Waszyngtona Street, 15-274 Bialystok, Poland; (D.L.); (U.D.)
- Correspondence: or
| | | | - Anna Pryczynicz
- Department of General Pathomorphology, Medical University of Bialystok, 15-089 Bialystok, Poland; (K.G.-U.); (A.P.)
| | - Dariusz Lebensztejn
- Department of Pediatrics, Gastroenterology, Hepatology, Nutrition and Allergology, Medical University of Bialystok, 17 Waszyngtona Street, 15-274 Bialystok, Poland; (D.L.); (U.D.)
| | - Urszula Daniluk
- Department of Pediatrics, Gastroenterology, Hepatology, Nutrition and Allergology, Medical University of Bialystok, 17 Waszyngtona Street, 15-274 Bialystok, Poland; (D.L.); (U.D.)
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Early Change in Fecal Calprotectin Predicts One-Year Outcome in Children Newly Diagnosed With Ulcerative Colitis. J Pediatr Gastroenterol Nutr 2022; 74:72-78. [PMID: 34433783 DOI: 10.1097/mpg.0000000000003291] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
INTRODUCTION While fecal calprotectin (FC) is used to assess disease activity in ulcerative colitis (UC) there are little data concerning the role of serial FC levels at diagnosis in predicting clinical course. We sought to determine whether FC at diagnosis or early change following therapy predicts clinical outcomes in pediatric UC.Methods: Children with newly diagnosed UC were treated with standardized regimens of mesalamine or corticosteroids (CS). CS tapering and escalation to additional therapy or colectomy were by protocol. Patients with baseline or week 4 or week 12 FC levels were included in the analysis. Our primary outcome was CS-free remission on mesalamine at week 52. We compared the prognostic value of a baseline FC as well as a change in FC by week 4 or week 12 in predicting clinical outcomes. RESULTS The study included 352 children (113 initial mesalamine, 239 initial CS, mean age 12.6 years) with UC. At Week 52, 135 (38.3%), 84 (23.8%), and 19 (5.4%) children achieved CS-free remission, needed anti-tumor necrosis factor therapy or had colectomy respectively. Baseline FC was not associated with CS-free remission at week 52. However, both week 4 (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.901.00) and week 12 FC levels (OR 0.91, 95% CI 0.87-0.96) were associated with outcomes, with the latter having a stronger association with CS-free remission. Patients with a >75% decrease by 12 weeks, had a 3-fold increased likelihood of CS-free remission at 1 year. DISCUSSION Longitudinal changes in FC may predict 1 year outcomes better than values at diagnosis in children with a new diagnosis of UC.
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Nardone OM, Iacucci M, Ghosh S, Castiglione F. Can a transition clinic bridge the gap between paediatric and adult inflammatory bowel disease care models? Dig Liver Dis 2020; 52:516-527. [PMID: 32234418 DOI: 10.1016/j.dld.2020.02.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 02/19/2020] [Accepted: 02/24/2020] [Indexed: 02/06/2023]
Abstract
Transition care in inflammatory bowel disease is increasingly recognized as challenging given the inherent differences between paediatric and adult health care models, disease characteristics and treatment strategies. Transition is a dynamic process involving adolescents and young adults that are moving from a paediatric to an adult health care setting, and it should be flexible, continually updated and tailored to each patient. The implementation of a transition clinic is essential given the increasing incidence of the paediatric population with inflammatory bowel disease and the lifelong impact of this disease. The key question is when and how to structure transition according to the adolescent's clinical, psycho-social, educational needs and expectations to ensure continuity of care. In the attempt to improve the management of transition in inflammatory bowel disease and address the wide gap between adult and child care, we provide an update of the transition clinic and we propose a "treat to target" approach in transition to facilitate an effective and successful transition programme. In the changing landscape of the treatment of inflammatory bowel disease, further studies are necessary to determine the role of the transition clinic in determining the choice and strategy of therapy and its monitoring and the adoption of newer strategies such as biomarkers guided treating to target.
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Affiliation(s)
- Olga Maria Nardone
- Institute of Translational Medicine and Institute of Immunology and Immunotherapy, University of Birmingham, UK; Gastroenterology, Department of Clinical Medicine and Surgery University Federico II of Naples, Italy.
| | - Marietta Iacucci
- Institute of Translational Medicine and Institute of Immunology and Immunotherapy, University of Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK; NIHR Biomedical Research Centre, University of Birmingham and University Hospitals NHS Foundation Trust Birmingham, UK; Gastroenterology, University of Calgary, Calgary, Canada
| | - Subrata Ghosh
- Institute of Translational Medicine and Institute of Immunology and Immunotherapy, University of Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK; NIHR Biomedical Research Centre, University of Birmingham and University Hospitals NHS Foundation Trust Birmingham, UK; Gastroenterology, University of Calgary, Calgary, Canada
| | - Fabiana Castiglione
- Gastroenterology, Department of Clinical Medicine and Surgery University Federico II of Naples, Italy
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Knyazev OV, Kagramanova AV, Korneeva IA, Noskova KK, Belousov SV, Parfenov AI. The use of fecal calprotectin in monitoring activity of inflammatory bowel diseases. TERAPEVT ARKH 2019; 91:53-61. [PMID: 31094477 DOI: 10.26442/00403660.2019.04.000229] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
AIM To compare fecal calprotectin (FC) concentration with laboratory and diagnostic methods in patients with inflammatory bowel diseases (IBD). MATERIALS AND METHODS The level of FC was measured in 110 patients with established IBD. Crohn diseases (CD) was diagnosed in 50 patients, ileocolitis - in 38 and terminal ileitis in 12 individuals. Ulcerative colitis (UC) was diagnosed in 60 patients, total colitis in 35, left-side colitis in 21 and 4 patients have proctitis. Laboratory data include measurement of FC, leukocytes, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), fecal occult blood. All patients underwent colonoileoscopy (CIS) at the start of disease flare and after 12 weeks of treatment. RESULTS We found linear correlation between level of FCP and endoscopic activity of CD, analyzing FCP level and endoscopic activity of CD before (during disease flare) and after 12 weeks treatment (r=0.66, p<0.001). Linear correlation between FCP and SES-CD sustained after 12 weeks of treatment (r=0.77, p<0.001). We revealed correlation between FCP concentration. And CRP level (r=0.59, p<0.05). The linear correlation was detected between FCP and endoscopic activity of UC (r=0.88, p<0.001) before the treatment. After 12 weeks of treatment linear correlation was shown between FCP and Meyo scale (r=0.73, p<0.001). IBD patients with FCP more than 200 mcg/g have high risk of disease reccurence in short-term period of time (HR - 8.33; 95% CI 2.05-33.8; χ2 - 11.85; p<0.001) and (HR - 2.7; 95% CI 1.1-6.6; χ2 - 5.3; p<0.05), accordingly. CONCLUSION Increased FCP level indicates poor effectiveness of treatment and high risk of reccurence. The level of FCP correlates strongly with recent laboratory and diagnostic indices of activity and enables to determine patients with high risk of reccurence. Thus, thorough monitoring, including additional procedures, contributes to just-in-time treatment modification.
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Affiliation(s)
- O V Knyazev
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
| | - A V Kagramanova
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
| | - I A Korneeva
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
| | - K K Noskova
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
| | - S V Belousov
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
| | - A I Parfenov
- A.S. Loginov Moscow Clinical Research and Practical Center of the Department of Health of Moscow, Moscow, Russia
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Shores DR, Everett AD. Children as Biomarker Orphans: Progress in the Field of Pediatric Biomarkers. J Pediatr 2018; 193:14-20.e31. [PMID: 29031860 PMCID: PMC5794519 DOI: 10.1016/j.jpeds.2017.08.077] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 08/04/2017] [Accepted: 08/30/2017] [Indexed: 12/20/2022]
Affiliation(s)
- Darla R Shores
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD.
| | - Allen D Everett
- Division of Cardiology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD
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Ohem J, Hradsky O, Zarubova K, Copova I, Bukovska P, Prusa R, Malickova K, Bronsky J. Evaluation of Infliximab Therapy in Children with Crohn's Disease Using Trough Levels Predictors. Dig Dis 2017; 36:40-48. [PMID: 28817809 DOI: 10.1159/000477962] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Accepted: 06/01/2017] [Indexed: 02/02/2023]
Abstract
BACKGROUND In adults, infliximab (IFX) levels correlate with disease activity, and antibodies to IFX (ATIs) predict treatment failure. We aimed to determine the association of IFX levels and ATIs with disease activity in a paediatric population. We prospectively collected blood, stool, and clinical data from 65 patients (age 10.5-15.1 years) with Crohn's disease (CD) before IFX administration, and measured IFX trough levels, ATIs, and faecal calprotectin levels (CPT). Samples were collected during maintenance therapy. We used multivariate analysis to identify the predictors of IFX levels. SUMMARY Lower levels of IFX were associated with ATIs positivity (OR 0.027, 95% CI 0.009-0.077). Higher C-reactive protein (CRP) level, erythrocyte sedimentation rate, and CPT levels were found in patients with lower IFX levels. The optimal combination of sensitivity (0.5) and specificity (0.74) for disease activity was calculated for IFX levels ≥1.1 µg/mL using CRP level <5 mg/L as a marker of laboratory remission. In a model that used CPT ≤100 µg/g as the definition of remission, the optimal IFX trough level was 3.5 µg/mL. No independent association between remission and ATIs was found in our study population. However, we found an independentz association between IFX levels and serum albumin levels (OR 1.364, 95% CI 1.169-1.593), p < 0.001. Key Messages: The paediatric population was similar to adult populations in terms of the association between IFX and ATIs as well as between IFX and disease activity.
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Affiliation(s)
- Jan Ohem
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles, University and Motol University Hospital, Prague, Czech Republic
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