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Minato I, Mena P, Ricciardiello L, Scaioli E, Belluzzi A, Rotondo E, Derlindati E, Montanini B, Michelini C, Tosi N, Agullò Garcià V, Picone G, Mengucci C, Dobani S, Salamanca P, Rosi A, Dall'Asta M, Bresciani L, Curti C, Spisni E, Dei Cas A, Bordoni A, Tomás-Barberán FA, Ferguson LR, Del Rio D, Danesi F. Evidence for a Modulatory Effect of a 12-Week Pomegranate Juice Intervention on the Transcriptional Response in Inflammatory Bowel Disease Patients Reducing Fecal Calprotectin Levels: Findings From a Proof-of-Principle Study. Mol Nutr Food Res 2025:e70067. [PMID: 40255128 DOI: 10.1002/mnfr.70067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 03/27/2025] [Accepted: 04/02/2025] [Indexed: 04/22/2025]
Abstract
This study aimed at investigating the effects of pomegranate juice (POMJ) consumption on inflammatory biomarkers and gene expression in patients with inflammatory bowel disease (IBD) in clinical remission. In this randomized, placebo-controlled trial, 16 subjects with IBD in remission consumed POMJ or placebo for 12 weeks. POMJ consumption significantly reduced fecal calprotectin (FC) and plasma endotoxin levels. Transcriptomic analysis of peripheral blood mononuclear cells revealed upregulation of genes involved in mucosal immunity, including aryl hydrocarbon receptor (AHR), neutrophil cytosolic factor 4 (NCF4), and nuclear factor, interleukin 3 regulated (NFIL3). Urolithin metabotypes were predominantly of the B type, associated with intestinal dysbiosis. No significant changes were observed in serum inflammatory markers or colonic mucosal cytokine expression. POMJ consumption reduced markers of intestinal inflammation and modulated gene expression related to mucosal immunity and barrier function in patients with IBD. These findings suggest the potential of POMJ as a beneficial dietary intervention for maintaining remission in IBD, highlighting the promise of targeted nutritional strategies in managing chronic inflammatory conditions. Further research is needed to elucidate the long-term clinical implications of these molecular changes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03000101.
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Affiliation(s)
- Ilaria Minato
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
- Interdepartmental Center for Innovation in Health Products, Biopharmanet-TEC, University of Parma, Parma, Italy
| | - Pedro Mena
- Department of Food and Drug, University of Parma, Parma, Italy
- Microbiome Research Hub, University of Parma, Parma, Italy
| | - Luigi Ricciardiello
- IRCCS - St. Orsola-Malpighi Hospital, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | | | - Enrica Rotondo
- Department of Agricultural and Food Sciences, University of Bologna, Cesena, Italy
| | - Eleonora Derlindati
- Department of Agricultural and Food Sciences, University of Bologna, Cesena, Italy
| | - Barbara Montanini
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
- Interdepartmental Center for Innovation in Health Products, Biopharmanet-TEC, University of Parma, Parma, Italy
| | | | - Nicole Tosi
- Department of Food and Drug, University of Parma, Parma, Italy
| | | | - Gianfranco Picone
- Department of Agricultural and Food Sciences, University of Bologna, Cesena, Italy
| | - Carlo Mengucci
- Department of Agricultural and Food Sciences, University of Bologna, Cesena, Italy
| | - Sara Dobani
- Department of Food and Drug, University of Parma, Parma, Italy
| | | | - Alice Rosi
- Department of Food and Drug, University of Parma, Parma, Italy
| | - Margherita Dall'Asta
- Department of Food and Drug, University of Parma, Parma, Italy
- Department of Animal Science, Food and Nutrition, Università Cattolica del Sacro Cuore, Piacenza, Italy
| | | | - Claudio Curti
- Department of Food and Drug, University of Parma, Parma, Italy
| | - Enzo Spisni
- Department of Biological, Geological, and Environmental Sciences, University of Bologna, Bologna, Italy
| | - Alessandra Dei Cas
- Department of Medicine and Surgery - Division of Endocrinology and Metabolic Diseases, University of Parma, Parma, Italy
| | - Alessandra Bordoni
- Department of Agricultural and Food Sciences, University of Bologna, Cesena, Italy
| | | | - Lynnette R Ferguson
- Department of Nutrition, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Daniele Del Rio
- Department of Food and Drug, University of Parma, Parma, Italy
- Microbiome Research Hub, University of Parma, Parma, Italy
| | - Francesca Danesi
- Department of Agricultural and Food Sciences, University of Bologna, Cesena, Italy
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Hodgkiss R, Acharjee A. Unravelling metabolite-microbiome interactions in inflammatory bowel disease through AI and interaction-based modelling. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167618. [PMID: 39662756 DOI: 10.1016/j.bbadis.2024.167618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 11/20/2024] [Accepted: 12/03/2024] [Indexed: 12/13/2024]
Abstract
Inflammatory Bowel Diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract and colon affecting approximately 7 million individuals worldwide. The knowledge of specific pathology and aetiological mechanisms leading to IBD is limited, however a reduced immune system, antibiotic use and reserved diet may initiate symptoms. Dysbiosis of the gut microbiome, and consequently a varied composition of the metabolome, has been extensively linked to these risk factors and IBD. Metagenomic sequencing and liquid-chromatography mass spectrometry (LC-MS) of N = 220 fecal samples by Fransoza et al., provided abundance data on microbial genera and metabolites for use in this study. Identification of differentially abundant microbes and metabolites was performed using a Wilcoxon test, followed by feature selection of random forest (RF), gradient-boosting (XGBoost) and least absolute shrinkage operator (LASSO) models. The performance of these features was then validated using RF models on the Human Microbiome Project 2 (HMP2) dataset and a microbial community (MICOM) model was utilised to predict and interpret the interactions between key microbes and metabolites. The Flavronifractor genus and microbes of the families Lachnospiraceae and Oscillospiraceae were found differential by all models. Metabolic pathways commonly influenced by such microbes in IBD were CoA biosynthesis, bile acid metabolism and amino acid production and degradation. This study highlights distinct interactive microbiome and metabolome profiles within IBD and the highly potential pathways causing disease pathology. It therefore paves way for future investigation into new therapeutic targets and non-invasive diagnostic tools for IBD.
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Affiliation(s)
- Rebecca Hodgkiss
- College of Medicine and Health, Cancer and Genomic Sciences, University of Birmingham, B15 2TT Birmingham, UK
| | - Animesh Acharjee
- College of Medicine and Health, Cancer and Genomic Sciences, University of Birmingham, B15 2TT Birmingham, UK; Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, B15 2TT Birmingham, UK; MRC Health Data Research UK (HDR), Midlands Site, UK; Centre for Health Data Research, University of Birmingham, B15 2TT, UK.
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Lima Oliveira M, Lima NS, Khara Renaud G, Estrada A, Buitrago D, Hamm A, Nadeem S, Naylor KB, Chen Z, Yanez B, Booms E, Searcy J, Biggers A, Tussing-Humphreys LM. Design of a mindfulness intervention to reduce risk factors for colorectal cancer among at-risk Black women in Chicago. J Appl Physiol (1985) 2024; 137:1484-1493. [PMID: 39417824 PMCID: PMC11573258 DOI: 10.1152/japplphysiol.00608.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 09/17/2024] [Accepted: 10/05/2024] [Indexed: 10/19/2024] Open
Abstract
Chronic stress can directly and indirectly promote carcinogenesis through immune, metabolic, and microbial pathways. Our overarching hypothesis is that reducing chronic stress will have important implications for colorectal cancer (CRC) risk reduction among vulnerable and high-risk populations. A promising approach for reducing chronic stress is mindfulness. Mindfulness is a meditation-based technique that achieves a state of mind that is used to experience higher awareness or consciousness. Existing small studies suggest mindfulness can positively regulate stress response in a way that translates to anticancer effects, including reduced systemic inflammation. We propose to evaluate an 8-wk mindfulness intervention delivered in a hybrid format (synchronous and asynchronous sessions) among 40 Black women at elevated risk of CRC who reside in vulnerable communities and who report moderate to high perceived stress. At baseline and postintervention, participants will provide blood, hair, and stool; undergo body composition analysis; and complete mood and lifestyle-related surveys. The specific aims are to assess the feasibility and acceptability of the intervention and explore changes on stress, weight, fasting glucose, inflammation markers, and the gut microbiota-risk markers and risk pathways associated with CRC. The data generated through this project will inform if mindfulness is a feasible option for CRC risk reduction among high-risk individuals.NEW & NOTEWORTHY We propose to evaluate an 8-wk mindfulness intervention delivered in a hybrid format (synchronous and asynchronous sessions) among 40 Black women at elevated risk of CRC who reside in vulnerable communities and who report moderate to high perceived stress. The specific aims are to assess the feasibility and acceptability of the intervention and explore changes on stress, weight, fasting glucose, inflammation markers, and the gut microbiota-risk markers and risk pathways associated with CRC.
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Affiliation(s)
- Manoela Lima Oliveira
- Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, Illinois, United States
- University of Illinois Cancer Center, Chicago, Illinois, United States
| | - Natalia Salvatierra Lima
- Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, Illinois, United States
| | | | - Andy Estrada
- Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Diana Buitrago
- Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Alyshia Hamm
- Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, Illinois, United States
| | - Saba Nadeem
- Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, Illinois, United States
| | - Keith B Naylor
- University of Illinois Cancer Center, Chicago, Illinois, United States
- College of Medicine, University of Illinois Chicago, Illinois, United States
| | - Zhengjia Chen
- University of Illinois Cancer Center, Chicago, Illinois, United States
| | - Betina Yanez
- Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Emily Booms
- Biology Department, Northeastern Illinois University, Chicago, Illinois, United States
| | - Jasmin Searcy
- Department of Psychology, University of Illinois Chicago, Chicago, Illinois, United States
| | - Alana Biggers
- College of Medicine, University of Illinois Chicago, Illinois, United States
| | - Lisa Marie Tussing-Humphreys
- Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, Illinois, United States
- University of Illinois Cancer Center, Chicago, Illinois, United States
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Tokushima K, Jimbo K, Suzuki M, Endo Y, Hibio M, Maruyama K, Kashiwagi K, Arai N, Sato M, Kudo T, Hoshino E, Ohtsuka Y, Shimizu T. Differentiation of Active Ulcerative Colitis vs Noninflammatory Bowel Disease Proctitis by Transperineal Superb Microvascular Imaging. Inflamm Bowel Dis 2024; 30:1103-1111. [PMID: 37643765 DOI: 10.1093/ibd/izad186] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Indexed: 08/31/2023]
Abstract
BACKGROUND Transabdominal ultrasonography and transperineal ultrasonography (TPUS) appear correspond to colonoscopy (CS) for evaluating ulcerative colitis (UC) activity, but their utility in UC diagnosis remains unclear. This research compared the accuracy of TPUS and CS for assessing rectal activity and differentiating noninflammatory bowel disease proctitis from UC in pediatric cases. METHODS The study is a blinded, prospective, and controlled trial. Prospectively, values of fecal calprotectin (FCP) and findings of the TPUS and CS were compared between child cases of UC and non-IBD proctitis. Findings of rectal wall thickening (RWT), rectal wall flow (RWF) on power Doppler, and microvascular signal at wall circumference (MSWC) on monochrome superb microvascular imaging assessed using TPUS were compared with the CS. RESULTS Thirty patients with Mayo endoscopic subscore (MES) 0 to 1 UC, 57 with MES 2 to 3 UC, and 44 with proctitis were registered. Fecal calprotectin, RWF, and MSWC indicated significant differences among the groups (P < .05). Rectal wall thickening showed no significant difference between MES 0-1 and proctitis (P = .76). Rectal wall thickening and MSWC were independent predictors of endoscopic activity of UC, resulting in a sensitivity and specificity of 100% for RWT ≥4.5 mm and positive MSWC. Fecal calprotectin and RWF were independent predictors for differentiating MES 0 to 1 and proctitis, and FCP and RWT were independent predictors for differentiating MES 2 to 3 and proctitis. Sensitivity and specificity were 77.2% and 80.9%, respectively, for FCP >242.5 μg/g and RWF negative; and they were both 100% for RWT >4.1 mm and MSWC positive. CONCLUSIONS Transperineal ultrasonography with mSMI may enable the evaluation of rectal activity and differentiation of UC from non-IBD proctitis with accuracy comparable to endoscopy.
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Affiliation(s)
- Kaori Tokushima
- Department of Pediatrics, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo- ku, Tokyo 113-8421, Japan
| | - Keisuke Jimbo
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Mitsuyoshi Suzuki
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Yoshiko Endo
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Musashi Hibio
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Kimiko Maruyama
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Kosuke Kashiwagi
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Nobuyasu Arai
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Masamichi Sato
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Takahiro Kudo
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Eri Hoshino
- Division of Policy Evaluation, Department of Health Policy, Research Institute, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan
| | - Yoshikazu Ohtsuka
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo- ku, Tokyo 113-8421, Japan
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Al-Beltagi M, Saeed NK, Bediwy AS, Elbeltagi R. Fecal calprotectin in pediatric gastrointestinal diseases: Pros and cons. World J Clin Pediatr 2024; 13:93341. [PMID: 38948001 PMCID: PMC11212754 DOI: 10.5409/wjcp.v13.i2.93341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 04/28/2024] [Accepted: 05/14/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND Fecal calprotectin is a valuable biomarker for assessing intestinal inflammation in pediatric gastrointestinal diseases. However, its role, pros, and cons in various conditions must be comprehensively elucidated. AIM To explore the role of fecal calprotectin in pediatric gastrointestinal diseases, including its advantages and limitations. METHODS A comprehensive search was conducted on PubMed, PubMed Central, Google Scholar, and other scientific research engines until February 24, 2024. The review included 88 research articles, 56 review articles, six meta-analyses, two systematic reviews, two consensus papers, and two letters to the editors. RESULTS Fecal calprotectin is a non-invasive marker for detecting intestinal inflammation and monitoring disease activity in pediatric conditions such as functional gastrointestinal disorders, inflammatory bowel disease, coeliac disease, coronavirus disease 2019-induced gastrointestinal disorders, gastroenteritis, and cystic fibrosis-associated intestinal pathology. However, its lack of specificity and susceptibility to various confounding factors pose challenges in interpretation. Despite these limitations, fecal calprotectin offers significant advantages in diagnosing, monitoring, and managing pediatric gastrointestinal diseases. CONCLUSION Fecal calprotectin holds promise as a valuable tool in pediatric gastroenterology, offering insights into disease activity, treatment response, and prognosis. Standardized protocols and guidelines are needed to optimize its clinical utility and mitigate interpretation challenges. Further research is warranted to address the identified limitations and enhance our understanding of fecal calprotectin in pediatric gastrointestinal diseases.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatric, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Manama, Bahrain
- Department of Pediatrics, University Medical Center, Dr. Sulaiman Al Habib Medical Group, Bahrain, Manama 26671, Manama, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Manama, Bahrain
- Medical Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Bahrain, Busaiteen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Tanta 31527, Alghrabia, Egypt
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Manama, Bahrain
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Manama, Bahrain
| | - Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland - Bahrain, Busiateen 15503, Muharraq, Bahrain
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Castellano MA, Scheeffer V, Petersen V, da Silveira TR. Evaluation of bowel wall flow by color Doppler ultrasound in the assessment of inflammatory bowel disease activity in pediatric patients. Radiol Bras 2023; 56:242-247. [PMID: 38204905 PMCID: PMC10775812 DOI: 10.1590/0100-3984.2023.0039-en] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 05/29/2023] [Accepted: 07/27/2023] [Indexed: 01/12/2024] Open
Abstract
Objective To assess inflammatory bowel disease (IBD) activity with Doppler ultrasound in pediatric patients, comparing the accuracy of the ultrasound findings with that of the concentrations of fecal calprotectin (FC). Materials and Methods In a consecutive series, we evaluated 53 examinations of 44 pediatric patients seen between 2014 and 2020: 28 with Crohn's disease, 15 with ulcerative colitis, and one with IBD unclassified. The diagnosis of IBD was made in accordance with the Porto criteria. The alteration studied in the greatest detail was bowel wall flow, which was classified by the lead investigator and two pediatric radiologists, all of whom were blinded to the FC concentrations and the other ultrasound findings. Bowel wall flow was categorized as low if there were up to 2 Doppler ultrasound signals/cm2, moderate if there were 3-5 signals/cm2, and high if there were more than 5 signals/cm2. Results The agreement among the radiologists was substantial (kappa = 0.73). In cases in which ultrasound showed low bowel wall flow, the median FC concentration was 92 µg/g (interquartile range, 33-661 µg/g), whereas it was 2,286 µg/g (interquartile range, 1,728-5,612 µg/g) in those in which ultrasound showed high bowel wall flow. In the sample as a whole, the sensitivity and specificity of ultrasound was 89.7% and 92.0%, respectively, for the detection of inflammatory activity; 95.5% and 90.9%, respectively, for the detection of Crohn's disease; and 81.3% and 100.0%, respectively, for the detection of ulcerative colitis. Conclusion Ultrasound of the bowel wall showed a strong correlation with FC concentrations in the assessment of inflammatory activity in pediatric patients with IBD.
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Affiliation(s)
- Marco Aurélio Castellano
- Hospital da Criança Santo Antônio da Santa Casa de
Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil
- Hospital Moinhos de Vento, Porto Alegre, RS, Brazil
| | - Vanessa Scheeffer
- Hospital da Criança Santo Antônio da Santa Casa de
Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil
| | - Vanessa Petersen
- Hospital da Criança Santo Antônio da Santa Casa de
Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil
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Xia JY, Hepler C, Tran P, Waldeck NJ, Bass J, Prindle A. Engineered calprotectin-sensing probiotics for IBD surveillance in humans. Proc Natl Acad Sci U S A 2023; 120:e2221121120. [PMID: 37523538 PMCID: PMC10410751 DOI: 10.1073/pnas.2221121120] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 06/07/2023] [Indexed: 08/02/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a spectrum of autoimmune diseases affecting the gastrointestinal tract characterized by a relapsing and remitting course of gut mucosal inflammation. Disease flares can be difficult to predict, and the current practice of IBD disease activity surveillance through endoscopy is invasive and requires medical expertise. Recent advancements in synthetic biology raise the possibility that symbiotic microbes can be engineered to selectively detect disease biomarkers used in current clinical practice. Here, we introduce an engineered probiotic capable of detecting the clinical gold standard IBD biomarker, calprotectin, with sensitivity and specificity in IBD patients. Specifically, we identified a bacterial promoter in the probiotic strain Escherichia coli Nissle 1917 (EcN) which exhibits a specific expression increase in the presence of calprotectin. Using murine models of colitis, we show that the reporter signal is activated in vivo during transit of the GI tract following oral delivery. Furthermore, our engineered probiotic can successfully discriminate human patients with active IBD from those in remission and without IBD using patient stool samples, where the intensity of reporter signal quantitatively tracks with clinical laboratory-measured levels of calprotectin. Our pilot study sets the stage for probiotics that can be engineered to detect fecal calprotectin for precise noninvasive disease activity monitoring in IBD patients.
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Affiliation(s)
- Jonathan Y. Xia
- Division of Gastroenterology and Hepatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL60611
- Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL60611
| | - Chelsea Hepler
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL60611
| | - Peter Tran
- Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL60208
| | - Nathan J. Waldeck
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL60611
| | - Joseph Bass
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL60611
| | - Arthur Prindle
- Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL60611
- Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL60208
- Center for Synthetic Biology, Northwestern University, Evanston, IL60208
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McCurdy J, Nath A, Rosenberg H. How to assess and manage ulcerative colitis exacerbations in the emergency department. CAN J EMERG MED 2023; 25:190-192. [PMID: 36725785 DOI: 10.1007/s43678-023-00461-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Accepted: 01/13/2023] [Indexed: 02/03/2023]
Affiliation(s)
- Jeffrey McCurdy
- Department of Medicine, Clinical Investigator, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada
| | - Avik Nath
- Department of Emergency Medicine, University of Ottawa, Ottawa, Canada
| | - Hans Rosenberg
- Department of Emergency Medicine, University of Ottawa, Ottawa, Canada.
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Podolsky E, Hudek N, McCudden C, Presseau J, Yanikomeroglu S, Brouwers M, Brehaut JC. Choosing which in-hospital laboratory tests to target for intervention: a scoping review. Clin Chem Lab Med 2023; 61:388-401. [PMID: 36410390 PMCID: PMC9876731 DOI: 10.1515/cclm-2022-0910] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 11/03/2022] [Indexed: 11/23/2022]
Abstract
INTRODUCTION Some laboratory testing practices may be of low value, leading to wasted resources and potential patient harm. Our scoping review investigated factors and processes that developers report using to inform decisions about what tests to target for practice improvement. METHODS We searched Medline on May 30th, 2019 and June 28th, 2021 and included guidelines, recommendation statements, or empirical studies related to test ordering practices. Studies were included if they were conducted in a tertiary care setting, reported making a choice about a specific test requiring intervention, and reported at least one factor informing that choice. We extracted descriptive details, tests chosen, processes used to make the choice, and factors guiding test choice. RESULTS From 114 eligible studies, we identified 30 factors related to test choice including clinical value, cost, prevalence of test, quality of test, and actionability of test results. We identified nine different processes used to inform decisions regarding where to spend intervention resources. CONCLUSIONS Intervention developers face difficult choices when deciding where to put scarce resources intended to improve test utilization. Factors and processes identified here can be used to inform a framework to help intervention developers make choices relevant to improving testing practices.
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Affiliation(s)
- Eyal Podolsky
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
- Clinical Epidemiology Program, Centre for Practice Changing Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON, Canada
| | - Natasha Hudek
- Clinical Epidemiology Program, Centre for Practice Changing Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON, Canada
| | - Christopher McCudden
- Clinical Epidemiology Program, Centre for Practice Changing Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON, Canada
- Division of Biochemistry, Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, ON, Canada
- Eastern Ontario Regional Laboratory Association, Ottawa, ON, Canada
| | - Justin Presseau
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
- Clinical Epidemiology Program, Centre for Practice Changing Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON, Canada
| | - Sezgi Yanikomeroglu
- Clinical Epidemiology Program, Centre for Practice Changing Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON, Canada
| | - Melissa Brouwers
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
| | - Jamie C. Brehaut
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
- Clinical Epidemiology Program, Centre for Practice Changing Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON, Canada
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10
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Wolf PG, Bernabe BP, Oliveira ML, Hamm A, McLeod A, Olender S, Castellanos K, Loman BR, Gaskins HR, Fitzgibbon M, Tussing-Humphreys L. Effect of Diets Varying in Iron and Saturated Fat on the Gut Microbiota and Intestinal Inflammation: A Crossover Feeding Study among Older Females with Obesity. Nutr Cancer 2023; 75:876-889. [PMID: 36625531 PMCID: PMC10023443 DOI: 10.1080/01635581.2022.2163668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 12/23/2022] [Accepted: 12/23/2022] [Indexed: 01/11/2023]
Abstract
Obesity is considered an independent risk factor for colorectal cancer (CRC). Altered nutrient metabolism, particularly changes to digestion and intestinal absorption, may play an important role in the development of CRC. Iron can promote the formation of tissue-damaging and immune-modulating reactive oxygen species. We conducted a crossover, controlled feeding study to examine the effect of three, 3-week diets varying in iron and saturated fat content on the colonic milieu and systemic markers among older females with obesity. Anthropometrics, fasting venous blood and stool were collected before and after each diet. There was a minimum 3-week washout period between diets. Eighteen participants consumed the three diets (72% Black; mean age 60.4 years; mean body mass index 35.7 kg/m2). Results showed no effect of the diets on intestinal inflammation (fecal calprotectin) or circulating iron, inflammation, and metabolic markers. Pairwise comparisons revealed less community diversity between samples (beta diversity, calculated from 16S rRNA amplicon sequences) among participants when consuming a diet low in iron and high in saturated fat vs. when consuming a diet high in iron and saturated fat. More studies are needed to investigate if dietary iron represents a salient target for CRC prevention among individuals with obesity.
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Affiliation(s)
- Patricia G. Wolf
- Institute for Health Research and Policy, University of Illinois Chicago, Chicago, IL, USA
- University of Illinois Cancer Center, University of Illinois Chicago, Chicago, IL, USA
- Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA
- Department of Nutrition Science, Purdue University, West Lafayette, IN, USA
| | | | - Manoela Lima Oliveira
- Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, Illinois, USA
| | - Alyshia Hamm
- Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, Illinois, USA
| | - Andrew McLeod
- Institute for Health Research and Policy, University of Illinois Chicago, Chicago, IL, USA
- Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, Illinois, USA
| | - Sarah Olender
- Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, Illinois, USA
| | - Karla Castellanos
- Department of Medicine, University of Illinois Chicago, Chicago, Illinois, USA
| | - Brett R. Loman
- Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA
- Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA
| | - H. Rex Gaskins
- Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA
- Carl R. Woese Institute for Genomic Biology, Urbana, IL, USA
- Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA
- Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, IL, USA
| | - Marian Fitzgibbon
- Institute for Health Research and Policy, University of Illinois Chicago, Chicago, IL, USA
- University of Illinois Cancer Center, University of Illinois Chicago, Chicago, IL, USA
- Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA
| | - Lisa Tussing-Humphreys
- University of Illinois Cancer Center, University of Illinois Chicago, Chicago, IL, USA
- Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, Illinois, USA
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11
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Inciarte-Mundo J, Frade-Sosa B, Sanmartí R. From bench to bedside: Calprotectin (S100A8/S100A9) as a biomarker in rheumatoid arthritis. Front Immunol 2022; 13:1001025. [PMID: 36405711 PMCID: PMC9672845 DOI: 10.3389/fimmu.2022.1001025] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 10/19/2022] [Indexed: 12/30/2022] Open
Abstract
S100A9/S100A8 (calprotectin), a member of the S100 protein family, has been shown to play a pivotal role in innate immunity activation. Calprotectin plays a critical role in the pathogenesis of rheumatoid arthritis (RA), as it triggers chemotaxis, phagocyte migration and modulation of neutrophils and macrophages. Higher calprotectin levels have been found in synovial fluid, plasma, and serum from RA patients. Recent studies have demonstrated better correlations between serum or plasma calprotectin and composite inflammatory disease activity indexes than c-reactive protein (CRP) or the erythrocyte sedimentation rate (ESR). Calprotectin serum levels decreased after treatment, independently of the DMARD type or strategy. Calprotectin has shown the strongest correlations with other sensitive techniques to detect inflammation, such as ultrasound. Calprotectin independently predicts radiographic progression. However, its value as a biomarker of treatment response and flare after tapering is unclear. This update reviews the current understanding of calprotectin in RA and discusses possible applications as a biomarker in clinical practice.
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Affiliation(s)
- José Inciarte-Mundo
- Biological aggression and Response Mechanisms, Inflammatory joint diseases (IJDs), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Beatriz Frade-Sosa
- Rheumatology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Raimon Sanmartí
- Biological aggression and Response Mechanisms, Inflammatory joint diseases (IJDs), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain,Rheumatology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain,*Correspondence: Raimon Sanmartí,
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12
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Assessment of Exercise-Associated Gastrointestinal Perturbations in Research and Practical Settings: Methodological Concerns and Recommendations for Best Practice. Int J Sport Nutr Exerc Metab 2022; 32:387-418. [PMID: 35963615 DOI: 10.1123/ijsnem.2022-0048] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/26/2022] [Accepted: 07/07/2022] [Indexed: 12/14/2022]
Abstract
Strenuous exercise is synonymous with disturbing gastrointestinal integrity and function, subsequently prompting systemic immune responses and exercise-associated gastrointestinal symptoms, a condition established as "exercise-induced gastrointestinal syndrome." When exercise stress and aligned exacerbation factors (i.e., extrinsic and intrinsic) are of substantial magnitude, these exercise-associated gastrointestinal perturbations can cause performance decrements and health implications of clinical significance. This potentially explains the exponential growth in exploratory, mechanistic, and interventional research in exercise gastroenterology to understand, accurately measure and interpret, and prevent or attenuate the performance debilitating and health consequences of exercise-induced gastrointestinal syndrome. Considering the recent advancement in exercise gastroenterology research, it has been highlighted that published literature in the area is consistently affected by substantial experimental limitations that may affect the accuracy of translating study outcomes into practical application/s and/or design of future research. This perspective methodological review attempts to highlight these concerns and provides guidance to improve the validity, reliability, and robustness of the next generation of exercise gastroenterology research. These methodological concerns include participant screening and description, exertional and exertional heat stress load, dietary control, hydration status, food and fluid provisions, circadian variation, biological sex differences, comprehensive assessment of established markers of exercise-induced gastrointestinal syndrome, validity of gastrointestinal symptoms assessment tool, and data reporting and presentation. Standardized experimental procedures are needed for the accurate interpretation of research findings, avoiding misinterpreted (e.g., pathological relevance of response magnitude) and overstated conclusions (e.g., clinical and practical relevance of intervention research outcomes), which will support more accurate translation into safe practice guidelines.
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Marsal J, Barreiro-de Acosta M, Blumenstein I, Cappello M, Bazin T, Sebastian S. Management of Non-response and Loss of Response to Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel Disease. Front Med (Lausanne) 2022; 9:897936. [PMID: 35783628 PMCID: PMC9241563 DOI: 10.3389/fmed.2022.897936] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 05/25/2022] [Indexed: 11/30/2022] Open
Abstract
Anti-tumor necrosis factor (anti-TNF) therapy has been successfully used as first-line biologic treatment for moderate-to-severe inflammatory bowel disease (IBD), in both "step-up" and "top-down" approaches, and has become a cornerstone of IBD management. However, in a proportion of patients the effectiveness of anti-TNF therapy is sub-optimal. Either patients do not achieve adequate initial response (primary non-response) or they lose response after initial success (loss of response). Therapeutic drug monitoring determines drug serum concentrations and the presence of anti-drug antibodies (ADAbs) and can help guide treatment optimization to improve patient outcomes. For patients with low drug concentrations who are ADAb-negative or display low levels of ADAbs, dose escalation is recommended. Should response remain unchanged following dose optimization the question whether to switch within class (anti-TNF) or out of class (different mechanism of action) arises. If ADAb levels are high and the patient has previously benefited from anti-TNF therapy, then switching within class is a viable option as ADAbs are molecule specific. Addition of an immunomodulator may lead to a decrease in ADAbs and a regaining of response in a proportion of patients. If a patient does not achieve a robust therapeutic response with an initial anti-TNF despite adequate drug levels, then switching out of class is appropriate. In conjunction with the guidance above, other factors including patient preference, age, comorbidities, disease phenotype, extra-intestinal manifestations, and treatment costs need to be factored into the treatment decision. In this review we discuss current evidence in this field and provide guidance on therapeutic decision-making in clinical situations.
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Affiliation(s)
- Jan Marsal
- Department of Gastroenterology, Skåne University Hospital, Lund/Malmö, Sweden
- Department of Immunology, Lund University, Lund, Sweden
| | - Manuel Barreiro-de Acosta
- Gastroenterology Department, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - Irina Blumenstein
- Department of Internal Medicine 1, Gastroenterology, Hepatology and Clinical Nutrition, University Clinic Frankfurt, Frankfurt, Germany
| | - Maria Cappello
- Gastroenterology and Hepatology Section, Promise, University of Palermo, Palermo, Italy
| | - Thomas Bazin
- Department of Gastroenterology, Université Paris Saclay/UVSQ, INSERM, Infection and Inflammation, UMR 1173, AP-HP, Hôpital Ambroise Paré, Boulogne Billancourt, France
| | - Shaji Sebastian
- Inflammatory Bowel Disease (IBD) Unit, Hull University Teaching Hospitals National Health Service (NHS) Trust, Hull, United Kingdom
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14
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Screening for gastrointestinal and pancreatic diseases. Adv Clin Chem 2022; 108:129-153. [PMID: 35659059 DOI: 10.1016/bs.acc.2021.09.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Diagnosis of chronic gastrointestinal and pancreatic diseases is challenging because patients generally present with nonspecific symptoms, such as abdominal pain and chronic diarrhea, some of which can last for many years. Although stool assays are more sensitive than serum assays, the former has unique limitations that healthcare providers should be aware of. One algorithm to screen for chronic gastrointestinal and pancreatic issues is to perform stool testing to assess inflammatory, watery (osmotic) and malabsorptive conditions. This chapter will discuss several stool-based screening tests, the major disorders they screen for and clinical performance. Sections on assay and sample limitations are also included. Stool testing can provide valuable diagnostic, prognostic and treatment response information if both the laboratory and clinician understand the benefits and limitations of these assays.
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15
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Jelsness-Jørgensen LP, Moum B, Grimstad T, Jahnsen J, Hovde Ø, Frigstad SO, Bernklev T. The multidimensional fatigue inventory (MFI-20): psychometrical testing in a Norwegian sample of inflammatory bowel disease (IBD) patients. Scand J Gastroenterol 2022; 57:683-689. [PMID: 35076321 DOI: 10.1080/00365521.2022.2029939] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 01/02/2022] [Accepted: 01/11/2022] [Indexed: 02/04/2023]
Abstract
OBJECTIVES To evaluate the psychometric properties of the Norwegian version of the multidimensional fatigue inventory (MFI-20) in patients with inflammatory bowel disease. METHODS Participants were recruited from nine hospitals in the southeastern and western parts of Norway. Clinical and sociodemographic data were collected, and participants completed the MFI-20, as well as the Fatigue Questionnaire (FQ). In addition to a confirmatory factor analysis, validity, reliability, test-retest and responsiveness were evaluated. RESULTS In total, 410 patients were included. The Norwegian MFI-20 had an acceptable model fit when compared to the original five-dimensional structure. A positive correlation was observed between the dimensions of MFI-20 and the FQ. MFI-20 scores increased according to subjective disease activity, but no differences were observed when using a calprotectin cut-off < or > =250 µg/g mg/kg. All MFI-20 dimensions except 'reduced motivation' in both ulcerative colitis (UC) and Crohn's disease (CD) patients had alpha Cronbach alpha values ≥70, and test-retest reliability revealed good to excellent values. Merely one dimension (Reduced activity) in UC patients reporting improvement did not reach the threshold for acceptable responsiveness according to Guyatt statistics. CONCLUSIONS The Norwegian version of MFI-20 is valid, reliable and responsive. The instrument can safely be used in studies using fatigue as an endpoint.
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Affiliation(s)
- Lars-Petter Jelsness-Jørgensen
- Faculty of Health, Welfare and Organisation, Østfold University College, Halden, Norway
- Department of Gastroenterology, Østfold Hospital Trust, Grålum, Norway
| | - Bjørn Moum
- Department of Gastroenterology, Oslo University Hospital, Nydalen, Norway
- Institute of Clinical Medicine, University of Oslo, Blindern, Norway
| | - Tore Grimstad
- Department of Gastroenterology, Stavanger University Hospital, Stavanger, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Jørgen Jahnsen
- Institute of Clinical Medicine, University of Oslo, Blindern, Norway
- Department of Gastroenterology, Akershus University Hospital, Lillestrøm, Norway
| | - Øistein Hovde
- Institute of Clinical Medicine, University of Oslo, Blindern, Norway
- Department of Gastroenterology, Innlandet Hospital Trust, Gjøvik, Norway
| | - Svein Oskar Frigstad
- Institute of Clinical Medicine, University of Oslo, Blindern, Norway
- Department of Medicine, VestreViken Baerum Hospital, Gjettum, Norway
| | - Tomm Bernklev
- Institute of Clinical Medicine, University of Oslo, Blindern, Norway
- Vestfold Hospital Trust, Tønsberg, Norway
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Vieujean S, Caron B, Jairath V, Benetos A, Danese S, Louis E, Peyrin-Biroulet L. Is it time to include older adults in inflammatory bowel disease trials? A call for action. THE LANCET. HEALTHY LONGEVITY 2022; 3:e356-e366. [PMID: 36098310 DOI: 10.1016/s2666-7568(22)00060-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 03/04/2022] [Accepted: 03/09/2022] [Indexed: 02/07/2023] Open
Abstract
The therapeutic management of older patients with inflammatory bowel disease (IBD) is challenging, particularly because of the absence of evidence-based guidelines for these patients, who seem to frequently be excluded from clinical trials. In this systematic review we investigated the exclusion of older patients with IBD from phase 3 studies registered on PubMed and ClinicalTrials.gov, by assessing the upper limit of age exclusion criteria and the percentage of patients older than 65 years included in the trials. Exclusion criteria other than age were also recorded, and comorbidities were analysed separately. Our review of 222 phase 3 studies shows that older patients are frequently excluded from IBD clinical trials because of their age, which was used as an exclusion criterion in 129 (58%) of the 222 assessed trials. Of the 32 trials that detailed the percentage of included patients who were 65 years or older, only 763 (5·4%) patients of the 14 124 patients included were older than 65 years. In addition to age, patients were also excluded because of comorbidities (mainly renal, hepatic, and cardiovascular, and used as an exclusion criterion in 76% of trials), a history of dysplasia (45% of trials), and previous treatment for IBD (19% of trials). We propose a three-step process that should enable the inclusion of all older patients in IBD clinical trials, regardless of their age, comorbidities, and frailty.
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Affiliation(s)
- Sophie Vieujean
- Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium
| | - Bénédicte Caron
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Vipul Jairath
- Department of Medicine, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada; Alimentiv, London, ON, Canada
| | - Athanase Benetos
- Inserm, DCAC, University of Lorraine, Vandoeuvre-lès-Nancy, France; CHRU-Nancy Brabois, Department of Clinical Geriatrics, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Edouard Louis
- Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France.
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17
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Afif W, Sattin B, Dajnowiec D, Khanna R, Seow CH, Williamson M, Karra K, Wang Y, Gao LL, Bressler B. Ustekinumab Therapeutic Drug Monitoring-Impact on Clinical Practice: A Multicenter Cross-Sectional Observational Trial. Dig Dis Sci 2022; 67:3148-3157. [PMID: 34401983 PMCID: PMC9237009 DOI: 10.1007/s10620-021-07173-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 07/09/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS The value of ustekinumab (UST) therapeutic drug monitoring (TDM) in clinical practice remains unclear. This study examined the impact of UST TDM on clinical decision making in patients with Crohn's disease (CD). METHODS A total of 110 consecutive UST-treated CD patients were enrolled in this multicenter, single-arm cross-sectional study. During a single study visit, clinical decisions, disease characteristics, and serum and fecal samples were obtained. The primary outcome was congruency of the actual and two hypothetical clinical decisions based on provision of UST TDM (with and without fecal calprotectin [FCP]) to participating clinicians. Decisions were compared against those of a review panel. A sub-study retrospectively measured the associations of clinical outcomes at the next follow-up visit with serum UST concentration [UST]. RESULTS No differences in the pattern of decisions by clinicians were observed before and after provision of UST TDM (P = 1.0) or UST TDM + FCP (P = 0.86). However, 39% (TDM) and 50% (TDM + FCP) of hypothetical decisions differed from the initial decisions. The review panel's decisions differed with the addition of TDM + FCP (P = 0.0006), but not TDM alone (P = 0.16). The sub-study (n = 53) failed to detect an association between therapeutic serum [UST] at the initial study visit and clinical outcomes at the next visit. CONCLUSIONS In consecutive CD patients treated with UST, the addition of TDM into routine clinical practice did not significantly impact clinical decisions and there was no association between short-term clinical outcomes and serum [UST]. Further studies are warranted before clinicians routinely implement UST TDM into clinical practice.
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Affiliation(s)
- Waqqas Afif
- grid.14709.3b0000 0004 1936 8649Division of Gastroenterology and Hepatology, Department of Medicine, McGill University, Montreal, QC Canada
| | | | - Dorota Dajnowiec
- Medical Affairs, Janssen Inc, Toronto, ON Canada ,grid.467358.b0000 0004 0409 1325Present Address: Edwards Lifesciences Corp., One Edwards Way, Irvine, CA 92614 USA
| | - Reena Khanna
- grid.39381.300000 0004 1936 8884Division of Gastroenterology, University of Western Ontario, London, ON Canada
| | - Cynthia H. Seow
- grid.22072.350000 0004 1936 7697Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB Canada
| | | | - Kinda Karra
- Medical Affairs, Janssen Inc, Toronto, ON Canada ,Present Address: Merck Canada Inc., 16750 Trans-Canada Hwy, Kirkland, QC H9H 4M7 USA
| | - Yanli Wang
- grid.497530.c0000 0004 0389 4927Janssen R&D, Spring House, PA USA
| | - Long-long Gao
- grid.497530.c0000 0004 0389 4927Janssen R&D, Spring House, PA USA
| | - Brian Bressler
- grid.17091.3e0000 0001 2288 9830Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of British Columbia, 5th Floor, 2775 Laurel Street, Vancouver, BC V5Z 1M9 Canada
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Carrillo García P, Garmendia Prieto B, Albéniz Aguiriano L, Gómez Pavón J. [Inflammatory bowel disease in octogenarian woman]. Rev Esp Geriatr Gerontol 2021; 57:42-43. [PMID: 34924216 DOI: 10.1016/j.regg.2021.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 09/16/2021] [Accepted: 09/20/2021] [Indexed: 10/19/2022]
Affiliation(s)
- Pamela Carrillo García
- Servicio de Geriatría, Hospital Central de la Cruz Roja, San José y Santa Adela, Madrid, España.
| | - Blanca Garmendia Prieto
- Servicio de Geriatría, Hospital Central de la Cruz Roja, San José y Santa Adela, Madrid, España
| | - Luis Albéniz Aguiriano
- Servicio de Radiología, Hospital Central de la Cruz Roja, San José y Santa Adela, Madrid, España
| | - Javier Gómez Pavón
- Servicio de Geriatría, Hospital Central de la Cruz Roja, San José y Santa Adela, Madrid, España
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Wetwittayakhlang P, Lontai L, Gonczi L, Golovics PA, Hahn GD, Bessissow T, Lakatos PL. Treatment Targets in Ulcerative Colitis: Is It Time for All In, including Histology? J Clin Med 2021; 10:5551. [PMID: 34884252 PMCID: PMC8658443 DOI: 10.3390/jcm10235551] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 02/06/2023] Open
Abstract
The main therapeutic goal of ulcerative colitis (UC) is to induce and maintain remission to prevent long-term disease progression. Treat-to-target strategies, first introduced by the STRIDE consensus and updated in 2021, have shifted focus from symptomatic control toward more stringent objective endpoints. Today, patient monitoring should be based on a combination of biomarkers and clinical scores, while patient-reported outcomes could be used as short-term targets in monitoring disease activity and therapeutic response. In addition, endoscopic healing was the preferred long-term goal in UC. A Mayo endoscopic score (MES) ≤ 1 can be recommended as a minimum target. However, recent evidence suggests that more stringent endoscopic goals (MES of 0) are associated with superior outcomes. Recently, emerging data support that histological remission (HR) is a superior prognostic factor to endoscopic healing in predicting long-term remission. Despite not yet being recommended as a target, HR may become an important potential therapeutic goal in UC. However, it remains questionable if histological healing should be used as a routine assessment in addition to clinical, biomarker, and endoscopic targets in all patients. Therefore, in this review, our aim was to discuss the current evidence for the different treatment targets and their value in everyday clinical practice.
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Affiliation(s)
- Panu Wetwittayakhlang
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (P.A.G.); (G.D.H.); (T.B.)
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
| | - Livia Lontai
- First Department of Medicine, Semmelweis University, H-1083 Budapest, Hungary; (L.L.); (L.G.)
| | - Lorant Gonczi
- First Department of Medicine, Semmelweis University, H-1083 Budapest, Hungary; (L.L.); (L.G.)
| | - Petra A. Golovics
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (P.A.G.); (G.D.H.); (T.B.)
- Department of Gastroenterology, Hungarian Defence Forces, Medical Centre, H-1062 Budapest, Hungary
| | - Gustavo Drügg Hahn
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (P.A.G.); (G.D.H.); (T.B.)
- Graduate Course Sciences in Gastroenterology and Hepatology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-002, Brazil
| | - Talat Bessissow
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (P.A.G.); (G.D.H.); (T.B.)
| | - Peter L. Lakatos
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (P.A.G.); (G.D.H.); (T.B.)
- First Department of Medicine, Semmelweis University, H-1083 Budapest, Hungary; (L.L.); (L.G.)
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Gubatan J, Holman DR, Puntasecca CJ, Polevoi D, Rubin SJS, Rogalla S. Antimicrobial peptides and the gut microbiome in inflammatory bowel disease. World J Gastroenterol 2021; 27:7402-7422. [PMID: 34887639 PMCID: PMC8613745 DOI: 10.3748/wjg.v27.i43.7402] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/13/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
Antimicrobial peptides (AMP) are highly diverse and dynamic molecules that are expressed by specific intestinal epithelial cells, Paneth cells, as well as immune cells in the gastrointestinal (GI) tract. They play critical roles in maintaining tolerance to gut microbiota and protecting against enteric infections. Given that disruptions in tolerance to commensal microbiota and loss of barrier function play major roles in the pathogenesis of inflammatory bowel disease (IBD) and converge on the function of AMP, the significance of AMP as potential biomarkers and novel therapeutic targets in IBD have been increasingly recognized in recent years. In this frontier article, we discuss the function and mechanisms of AMP in the GI tract, examine the interaction of AMP with the gut microbiome, explore the role of AMP in the pathogenesis of IBD, and review translational applications of AMP in patients with IBD.
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Affiliation(s)
- John Gubatan
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Redwood City, CA 94063, United States
| | - Derek R Holman
- Department of Radiology, Molecular Imaging Program at Stanford , Stanford University, Stanford , CA 94305, United States
| | | | - Danielle Polevoi
- Stanford University School of Medicine, Stanford University, Stanford, CA 94063, United States
| | - Samuel JS Rubin
- Stanford University School of Medicine, Stanford University, Stanford, CA 94063, United States
| | - Stephan Rogalla
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Redwood City, CA 94063, United States
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21
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Barbosa JA, Rodrigues LA, Columbus DA, Aguirre JCP, Harding JCS, Cantarelli VS, Costa MDO. Experimental infectious challenge in pigs leads to elevated fecal calprotectin levels following colitis, but not enteritis. Porcine Health Manag 2021; 7:48. [PMID: 34429170 PMCID: PMC8383374 DOI: 10.1186/s40813-021-00228-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 08/06/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Fecal calprotectin is largely applied as a non-invasive intestinal inflammation biomarker in human medicine. Previous studies in pigs investigated the levels of fecal calprotectin in healthy animals only. Thus, there is a knowledge gap regarding its application during infectious diarrhea. This study investigated the usefulness of fecal calprotectin as a biomarker of intestinal inflammation in Brachyspira hyodysenteriae and Salmonella Typhimurium infected pigs. RESULTS Fecal samples from pigs with colitis (n = 18) were collected from animals experimentally inoculated with B. hyodysenteriae (n = 8) or from sham-inoculated controls (n = 3). Fecal samples from pigs with enteritis (n = 14) were collected from animals inoculated with Salmonella enterica serovar Typhimurium (n = 8) or from sham-inoculated controls (n = 4). For both groups, fecal samples were scored as: 0 = normal; 1 = soft, wet cement; 2 = watery feces; 3 = mucoid diarrhea; and 4 = bloody diarrhea. Fecal calprotectin levels were assayed using a sandwich ELISA, a turbidimetric immunoassay and a point-of-care dipstick test. Fecal calprotectin levels were greater in colitis samples scoring 4 versus ≤ 4 using ELISA, and in feces scoring 3 and 4 versus ≤ 1 using immunoturbidimetry (P < 0.05). No differences were found in calprotectin concentration among fecal scores for enteritis samples, regardless of the assay used. All samples were found below detection limits using the dipstick method. CONCLUSIONS Fecal calprotectin levels are increased following the development of colitis, but do not significantly change due to enteritis. While practical, the use of commercially available human kits present sensitivity limitations. Further studies are needed to validate the field application of calprotectin as a marker of intestinal inflammation.
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Affiliation(s)
- Jéssica A Barbosa
- Animal Science Department, Federal University of Lavras, Lavras, Minas Gerais, 37200-000, Brazil
| | - Lucas A Rodrigues
- Prairie Swine Centre, Inc., 2105 - 8th Street East, PO Box 21057, Saskatoon, SK, S7H 5N9, Canada
- Department of Animal and Poultry Science, University of Saskatchewan, 51 Campus Dr, Saskatoon, SK, S7N 5A8, Canada
| | - Daniel A Columbus
- Prairie Swine Centre, Inc., 2105 - 8th Street East, PO Box 21057, Saskatoon, SK, S7H 5N9, Canada
- Department of Animal and Poultry Science, University of Saskatchewan, 51 Campus Dr, Saskatoon, SK, S7N 5A8, Canada
| | - Juan C P Aguirre
- Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Dr, Saskatoon, SK, S7N 5B4, Canada
| | - John C S Harding
- Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Dr, Saskatoon, SK, S7N 5B4, Canada
| | - Vinícius S Cantarelli
- Animal Science Department, Federal University of Lavras, Lavras, Minas Gerais, 37200-000, Brazil
| | - Matheus de O Costa
- Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Dr, Saskatoon, SK, S7N 5B4, Canada.
- Department of Population Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 7, Utrecht, 3584 CL, The Netherlands.
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22
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Patel C, Keller L, Welsche S, Hattendorf J, Sayasone S, Ali SM, Ame SM, Coulibaly JT, Hürlimann E, Keiser J. Assessment of fecal calprotectin and fecal occult blood as point-of-care markers for soil-transmitted helminth attributable intestinal morbidity in a case-control substudy conducted in Côte d'Ivoire, Lao PDR and Pemba Island, Tanzania. EClinicalMedicine 2021; 32:100724. [PMID: 33554091 PMCID: PMC7851339 DOI: 10.1016/j.eclinm.2021.100724] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 01/06/2021] [Accepted: 01/07/2021] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND Infections with soil-transmitted helminths (STHs) may result in chronic inflammatory disorders affecting the human host. The objective of this study was to evaluate Fecal Calprotectin (FC) and Fecal Occult Blood (FOB) in individuals infected and non-infected with STHs to identify potential intestinal morbidity markers. METHODS Stool from participants diagnosed positive for Trichuris trichiura and concomitant STH infections from three countries was used to perform FC and FOB point-of-care assays. Simultaneously, identified STH negative participants underwent FC and FOB testing as controls. Potential associations between test results and determinants were analyzed using multivariable logistic regression. FINDINGS In total, 1034 T. trichiura infected cases (mostly light infections) and 157 STH negative controls were tested for FC and FOB. Among all participants tested, 18·5% had ≥ 50 µg/g FC concentration, while 14 (1·2%) were positive for FOB. No statistically significant association was found between T. trichiura infection or Ascaris lumbricoides co-infection and FC concentration, while an inverse association (odds ratio (OR): 0·45, 95% credible intervals (CrI): 0·26, 0·75) was found between hookworm co-infection and FC concentration. In Lao PDR, the proportion of participants in the ≥ 50 µg/g FC category was significantly higher in the oldest age category compared to the 5-11 years group (OR: 3·31, 95% CrI: 1·62, 7·24). Too few participants were found positive for FOB to derive any conclusions. INTERPRETATION Studies are needed to better understand the relationship between intestinal morbidity and STH infections. Suitable, standardized, low-cost markers of STH attributable morbidity to better monitor the impact of STH control interventions are necessary. FUNDING BMGF (OPP1153928).
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Affiliation(s)
- Chandni Patel
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Ladina Keller
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Sophie Welsche
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Jan Hattendorf
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Somphou Sayasone
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
- Department of International Program for Health in the Tropics, Lao Tropical and Public Health Institute, Vientiane, Lao People's Democratic Republic
| | - Said M. Ali
- Public Health Laboratory Ivo de Carneri, Chake Chake, Pemba, Zanzibar, Tanzania
| | - Shaali M. Ame
- Public Health Laboratory Ivo de Carneri, Chake Chake, Pemba, Zanzibar, Tanzania
| | - Jean Tenena Coulibaly
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
- Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire
- Department of Research and Development, Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Abidjan, Côte d'Ivoire
| | - Eveline Hürlimann
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Jennifer Keiser
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
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23
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D'Amico F, Nancey S, Danese S, Peyrin-Biroulet L. A Practical Guide for Faecal Calprotectin Measurement: Myths and Realities. J Crohns Colitis 2021; 15:152-161. [PMID: 32392336 DOI: 10.1093/ecco-jcc/jjaa093] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Faecal calprotectin [FC] is a valid and non-invasive marker of mucosal inflammation. It is widely used both in clinical trials and in daily clinical practice for patients with inflammatory bowel diseases, but currently no accepted standardization for FC testing is available. Our primary aim here was to provide a clinician's guide containing all the practical information on FC measurement in order to avoid any confounding factors, to minimize intra- and inter-individual variability in dosage, and to ensure a better and adequate interpretation of the results. METHODS We conducted a detailed search of the scientific literature in the PubMed/MEDLINE, EMBASE and Cochrane databases up to January 2020 to find all relevant and available articles on pre-analytical and analytical phases of FC measurement. RESULTS FC testing is a multi-step procedure consisting of a pre-analytical phase aimed to collect and process the stool sample and a subsequent analytical phase of FC measurement. Several factors can influence test results determining false positives or false negatives. Importantly, this faecal marker is mostly used for patient follow-up and as a predictor of treatment response. For this reason, any altered data may affect the physicians' decisions, negatively impacting on patient management. CONCLUSIONS This review provides for the first time practical advice to minimize dosage variability, although further dedicated studies are needed to compare commercially available tests and identify the best tools for the most precise and accurate FC measurement.
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Affiliation(s)
- Ferdinando D'Amico
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Stéphane Nancey
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre Benite, and Inserm U1111, CIRI, Lyon, France
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IBD Center, Department of Gastroenterology, Humanitas Research Hospital, Rozzano -IRCCS-, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
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24
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Maldonado-Arriaga B, Sandoval-Jiménez S, Rodríguez-Silverio J, Alcaráz- Estrada SL, Cortés-Espinosa T, Pérez-Cabeza de Vaca R, Shaw J, Mondragón-Terán P, Hernández-Cortez C, Suárez-Cuenca JA, Castro-Escarpulli G. Patient knowledge of fecal calprotectin in inflammatory bowel disease (IBD): An observational study in Mexico. F1000Res 2020; 9:1496. [PMID: 36072921 PMCID: PMC9418753 DOI: 10.12688/f1000research.27629.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/09/2020] [Indexed: 09/04/2024] Open
Abstract
Background: Fecal calprotectin (FC) can be a valuable tool to optimize health care for patients with inflammatory bowel disease (IBD). The objective of this observational study was to determine the level of knowledge of the FC test in Mexican patients with IBD. Methods: A self-report questionnaire was distributed via Facebook to patients with IBD. The survey consisted of 15 questions in two categories: the first category assessed knowledge of IBD diagnosis, and the second category assessed knowledge of the FC test. Results: In total, 460 patients with IBD participated, of which 83.9% (386) had ulcerative colitis (UC) and 16.0% (74) had Crohn's disease (CD). Regarding IBD diagnosis, 41.9% of participants stated that they did not know of a non-invasive test for fecal matter to identify inflammation of the colon. Regarding the FC test, 57.5% (UC) and 58.1% (CD) stated that they did not know about the test. Additionally, 65.8% (UC) and 51.3% (CD) of participants stated that they had never received the FC test and 82.6% (UC) and 77.0% (CD) recognized that the FC test was difficult to access in their medical practice. Furthermore, 66% (UC) and 52.7% (CD) of participants noted that their specialist doctor had never suggested the FC test to them, yet 89.1% (UC) and 87.8% (CD) stated that they would prefer FC analysis for their IBD follow-up assessments. Conclusions: There is little knowledge of the FC biomarker among Mexican patients with IBD. This suggests the need for greater dissemination of its use and scope as a biomarker in IBD.
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Affiliation(s)
- Brenda Maldonado-Arriaga
- Laboratorio de Metabolismo Experimental e Investigación Clínica; División de Investigación Clínica, ISSSTE, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, Ciudad de México, 03229, Mexico
- Hospital General de 2A Troncoso, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
- Laboratorio de Investigación Clínica y Ambiental. Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Calle Plan de Ayala s/n, Santo Tomás, Miguel Hidalgo, Ciudad de México, 11340, Mexico
| | - Sergio Sandoval-Jiménez
- Laboratorio de Metabolismo Experimental e Investigación Clínica; División de Investigación Clínica, ISSSTE, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, Ciudad de México, 03229, Mexico
- Hospital General de 2A Troncoso, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
| | - Juan Rodríguez-Silverio
- Escuela Superior de Medicina, Instituto Politécnico Nacional, Miguel Hidalgo, Ciudad de México, 11340, Mexico
| | - Sofía Lizeth Alcaráz- Estrada
- Unidad de Análisis y Referencia Virológica, ISSSTE, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, Ciudad de México, 03229, Mexico
| | - Tomás Cortés-Espinosa
- Clínica de Enfermedad Inflamatoria Intestinal, Servicio de Gastroenterología, ISSSTE, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, Ciudad de México, 03229, Mexico
| | - Rebeca Pérez-Cabeza de Vaca
- Coordinación de Investigación y División de Investigación Biomédica, ISSSTE, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, Ciudad de México, 03229, Mexico
| | - Jonathan Shaw
- Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, Broomhall, Sheffield, S10 2TG, UK
| | - Paul Mondragón-Terán
- Coordinación de Investigación y División de Investigación Biomédica, ISSSTE, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, Ciudad de México, 03229, Mexico
| | - Cecilia Hernández-Cortez
- Laboratorio de Bioquímica Microbiana, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Calle Plan de Ayala s/n, Santo Tomás, Miguel Hidalgo, Ciudad de México, 11340, Mexico
| | - Juan Antonio Suárez-Cuenca
- Laboratorio de Metabolismo Experimental e Investigación Clínica; División de Investigación Clínica, ISSSTE, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, Ciudad de México, 03229, Mexico
- Hospital General de 2A Troncoso, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
| | - Graciela Castro-Escarpulli
- Laboratorio de Investigación Clínica y Ambiental. Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Calle Plan de Ayala s/n, Santo Tomás, Miguel Hidalgo, Ciudad de México, 11340, Mexico
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25
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Maldonado-Arriaga B, Sandoval-Jiménez S, Rodríguez-Silverio J, Alcaráz- Estrada SL, Cortés-Espinosa T, Pérez-Cabeza de Vaca R, Shaw J, Mondragón-Terán P, Hernández-Cortez C, Suárez-Cuenca JA, Castro-Escarpulli G. Patient knowledge of fecal calprotectin in inflammatory bowel disease (IBD): An observational study in Mexico. F1000Res 2020; 9:1496. [PMID: 36072921 PMCID: PMC9418753 DOI: 10.12688/f1000research.27629.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/01/2021] [Indexed: 11/25/2022] Open
Abstract
Background: Fecal calprotectin (FC) can be a valuable tool to optimize health care for patients with inflammatory bowel disease (IBD). The objective of this observational study was to determine the level of knowledge of the FC test in Mexican patients with IBD. Methods: A self-report questionnaire was distributed via Facebook to patients with IBD. The survey consisted of 15 questions in two categories: the first category assessed knowledge of IBD diagnosis, and the second category assessed knowledge of the FC test. Results: In total, 460 patients with IBD participated, of which 83.9% (386) had ulcerative colitis (UC) and 16.0% (74) had Crohn's disease (CD). Regarding IBD diagnosis, 41.9% of participants stated that they did not know of a non-invasive test for fecal matter to identify inflammation of the colon. Regarding the FC test, 57.5% (UC) and 58.1% (CD) stated that they did not know about the test. Additionally, 65.8% (UC) and 51.3% (CD) of participants stated that they had never received the FC test and 82.6% (UC) and 77.0% (CD) recognized that the FC test was difficult to access in their medical practice. Furthermore, 66% (UC) and 52.7% (CD) of participants noted that their specialist doctor had never suggested the FC test to them, yet 89.1% (UC) and 87.8% (CD) stated that they would prefer FC analysis for their IBD follow-up assessments. Conclusions: There is little knowledge of the FC biomarker among Mexican patients with IBD. This suggests the need for greater dissemination of its use and scope as a biomarker in IBD.
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Affiliation(s)
- Brenda Maldonado-Arriaga
- Laboratorio de Metabolismo Experimental e Investigación Clínica; División de Investigación Clínica, ISSSTE, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, Ciudad de México, 03229, Mexico
- Hospital General de 2A Troncoso, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
- Laboratorio de Investigación Clínica y Ambiental. Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Calle Plan de Ayala s/n, Santo Tomás, Miguel Hidalgo, Ciudad de México, 11340, Mexico
| | - Sergio Sandoval-Jiménez
- Laboratorio de Metabolismo Experimental e Investigación Clínica; División de Investigación Clínica, ISSSTE, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, Ciudad de México, 03229, Mexico
- Hospital General de 2A Troncoso, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
| | - Juan Rodríguez-Silverio
- Escuela Superior de Medicina, Instituto Politécnico Nacional, Miguel Hidalgo, Ciudad de México, 11340, Mexico
| | - Sofía Lizeth Alcaráz- Estrada
- Unidad de Análisis y Referencia Virológica, ISSSTE, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, Ciudad de México, 03229, Mexico
| | - Tomás Cortés-Espinosa
- Clínica de Enfermedad Inflamatoria Intestinal, Servicio de Gastroenterología, ISSSTE, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, Ciudad de México, 03229, Mexico
| | - Rebeca Pérez-Cabeza de Vaca
- Coordinación de Investigación y División de Investigación Biomédica, ISSSTE, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, Ciudad de México, 03229, Mexico
| | - Jonathan Shaw
- Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, Broomhall, Sheffield, S10 2TG, UK
| | - Paul Mondragón-Terán
- Coordinación de Investigación y División de Investigación Biomédica, ISSSTE, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, Ciudad de México, 03229, Mexico
| | - Cecilia Hernández-Cortez
- Laboratorio de Bioquímica Microbiana, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Calle Plan de Ayala s/n, Santo Tomás, Miguel Hidalgo, Ciudad de México, 11340, Mexico
| | - Juan Antonio Suárez-Cuenca
- Laboratorio de Metabolismo Experimental e Investigación Clínica; División de Investigación Clínica, ISSSTE, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, Ciudad de México, 03229, Mexico
- Hospital General de 2A Troncoso, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
| | - Graciela Castro-Escarpulli
- Laboratorio de Investigación Clínica y Ambiental. Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Calle Plan de Ayala s/n, Santo Tomás, Miguel Hidalgo, Ciudad de México, 11340, Mexico
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26
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Porter AC, Aubrecht J, Birch C, Braun J, Cuff C, Dasgupta S, Gale JD, Hinton R, Hoffmann SC, Honig G, Linggi B, Schito M, Casteele NV, Sauer JM. Biomarkers of Crohn's Disease to Support the Development of New Therapeutic Interventions. Inflamm Bowel Dis 2020; 26:1498-1508. [PMID: 32840322 PMCID: PMC7500523 DOI: 10.1093/ibd/izaa215] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Currently, 2 coprimary end points are used by health authorities to determine the effectiveness of therapeutic interventions in patients with Crohn's disease (CD): symptomatic remission (patient-reported outcome assessment) and endoscopic remission (ileocolonoscopy). However, there is lack of accepted biomarkers to facilitate regulatory decision-making in the development of novel therapeutics for the treatment of CD. METHODS With support from the Helmsley Charitable Trust, Critical Path Institute formed the Crohn's Disease Biomarkers preconsortium (CDBpC) with members from the pharmaceutical industry, academia, and nonprofit organizations to evaluate the CD biomarker landscape. Biomarkers were evaluated based on biological relevance, availability of biomarker assays, and clinical validation data. RESULTS The CDBpC identified the most critical need as pharmacodynamic/response biomarkers to monitor disease activity in response to therapeutic intervention. Fecal calprotectin (FC) and serum C-reactive protein (CRP) were identified as biomarkers ready for the regulatory qualification process. A number of exploratory biomarkers and potential panels of these biomarkers was also identified for additional development. Given the different factors involved in CD and disease progression, a combination of biomarkers, including inflammatory, tissue injury, genetic, and microbiome-associated biomarkers, will likely have the most utility. CONCLUSIONS The primary focus of the Inflammatory Bowel Disease Regulatory Science Consortium will be development of exploratory biomarkers and the qualification of FC and CRP for IBD. The Inflammatory Bowel Disease Regulatory Science Consortium, focused on tools to support IBD drug development, will operate in the precompetitive space to share data, biological samples for biomarker testing, and assay information for novel biomarkers.
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Affiliation(s)
| | | | | | | | | | | | - Jeremy D Gale
- Pfizer Worldwide, Research, Development and Medical, Cambridge, MA, USA
| | - Robert Hinton
- The David R Clare and Margaret C Clare Foundation, Morristown, NJ, USA
| | | | | | | | | | - Niels Vande Casteele
- Department of Medicine, University of California San Diego, CA, USA,Robarts Clinical Trials Inc., London, ON, Canada
| | - John-Michael Sauer
- Critical Path Institute, AZ, USA,Address correspondence to: John-Michael Sauer, Critical Path Institute, 1730 E. River Rd Suite 200, Tucson, Arizona 85718, USA. E-mail:
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27
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Laserna-Mendieta EJ, Lucendo AJ. Faecal calprotectin in inflammatory bowel diseases: a review focused on meta-analyses and routine usage limitations. Clin Chem Lab Med 2020; 57:1295-1307. [PMID: 30785706 DOI: 10.1515/cclm-2018-1063] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Accepted: 11/28/2018] [Indexed: 12/12/2022]
Abstract
A growing body of evidence has been published about the usefulness of measuring calprotectin in faecal samples (FCAL) in inflammatory bowel disease (IBD) assessment, including diagnosis, monitoring of disease activity and relapse prediction. Several systematic reviews with meta-analyses compiling studies for each particular clinical setting have been carried out in recent years. Most of these were focused on the use of FCAL in IBD diagnosis and showed a relevant role for this marker in selecting patients with gastrointestinal symptoms who would not need a further examination by endoscopy. Although a lesser number of meta-analyses have been performed on the use of FCAL as a surrogate marker of disease activity, a close correlation between FCAL and endoscopic activity of IBD has been shown. With respect to the predictive capacity of FCAL for IBD relapse, a single meta-analysis published indicates that this role is more limited. Furthermore, FCAL thresholds vary considerably depending on the clinical setting and, what is more concerning, among different commercially available assays due to a lack of FCAL concentration interchangeability. Here, we summarise recent publications about the role and limitations of FCAL in IBD, with a special focus on meta-analyses, and give an overview of alternative faecal biomarkers.
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Affiliation(s)
- Emilio J Laserna-Mendieta
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain.,Clinical Laboratory, Hospital General de Villarrobledo, Villarrobledo, Spain
| | - Alfredo J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain.,Biomedical Research Network Centre for Liver and Digestive Diseases (CIBEREHD), Madrid, Spain
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28
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Vicente-Steijn R, Jansen J, Bisheshar R, Haagen IA. Analytical and clinical performance of the fully-automated LIAISONXL calprotectin immunoassay from DiaSorin in IBD patients. Pract Lab Med 2020; 21:e00175. [PMID: 32637525 PMCID: PMC7327250 DOI: 10.1016/j.plabm.2020.e00175] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 06/18/2020] [Indexed: 02/06/2023] Open
Abstract
Objectives Distinction between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) based on clinical symptoms is often difficult. In this study we assessed the performance of the fully-automated calprotectin immunoassay from DiaSorin in IBD diagnosis and follow-up and compared it to the EliA calprotectin 2 immunoassay. Design and Methods: The calprotectin immunoassay from DiaSorin run on the LIAISONXL was analytically and clinically validated and compared to the EliA calprotectin 2 immunoassay from Thermo Fisher Scientific run on the ImmunoCAP250. Five patient groups were measured (n = 303): IBD: ulcerative colitis (UC) and Crohn’s disease (CD); non-IBD: IBS, other gastrointestinal diseases and controls (healthy patients with no gastrointestinal disease). Results The calprotectin immunoassay of DiaSorin showed good analytical performance with frozen samples. The presence of blood in the stool can interfere with the measurement of calprotectin. Patients suffering from IBD (UC or CD) showed significant higher concentrations of fecal calprotectin compared to controls (UC:710 ± 921 mg/kg; CD:967 ± 1243 mg/kg; controls:11±8 mg/kg) using DiaSorin’s immunoassay. The remaining non-IBD groups showed no significant difference compared to controls. Follow-up patients (n = 9) showed a significant decrease in fecal calprotectin after treatment. At 50 mg/kg cut-off value, the negative predictive value for DiaSorin’s immunoassay was 96% and the positive predictive value 83% (sensitivity of 95% and specificity of 86%). Conclusions The lack of standardization contributes to the numerical differences between the two methods, but the qualitative conclusions do not differ. DiaSorin’s calprotectin immunoassay can be used both to distinguish between IBD and non-IBD patients as well as for follow-up of IBD patients.
New calprotectin immunoassay has a short sample preparation time and is easy to use. DiaSorin’s immunoassay can be used to distinguish between high and low risk IBD patients, as opposed to IBS. Differences observed between immunoassays are due to lack of standardization. Blood in the stool can effect the calprotectin measurement.
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Affiliation(s)
- R. Vicente-Steijn
- Laboratory of Hematology and Clinical Chemistry, OLVG Oost, Amsterdam, the Netherlands
- Corresponding author. OLVG Lab BV, OLVG Oost, Oosterpark 9, 1091 AC Amsterdam, the Netherlands.
| | - J.M. Jansen
- Department of Gastroenterology and Hepatology, OLVG Oost, Amsterdam, the Netherlands
| | - R. Bisheshar
- Laboratory of Hematology and Clinical Chemistry, OLVG Oost, Amsterdam, the Netherlands
| | - I.-A. Haagen
- Laboratory of Hematology and Clinical Chemistry, OLVG Oost, Amsterdam, the Netherlands
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Vernia F, Di Ruscio M, Stefanelli G, Viscido A, Frieri G, Latella G. Is fecal calprotectin an accurate marker in the management of Crohn's disease? J Gastroenterol Hepatol 2020; 35:390-400. [PMID: 31795013 DOI: 10.1111/jgh.14950] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 11/06/2019] [Accepted: 11/16/2019] [Indexed: 12/14/2022]
Abstract
Although lacking validated cutoff values, fecal calprotectin (FC), besides C-reactive protein, is considered the standard test for assessing disease activity in Crohn's disease (CD). The aim of the present review is to provide a general overview of the literature addressing the role of FC in the clinical and endoscopic assessment of disease activity in CD, seeking correlations with capsule endoscopy, response to therapy, prediction of relapse, and postoperative recurrence. A systematic search of the literature up to September 2019 was performed using Medline, Embase, and the Cochrane Library. Only papers written in English concerning FC in adult patients affected by CD were included. Pediatric studies, in vitro studies, animal studies, studies on blood/serum samples, and studies analyzing FC in ulcerative colitis or in both CD and ulcerative colitis were excluded. Out of 713 citations, 65 eligible studies were identified. FC showed high accuracy in the assessment of intestinal inflammation and response to therapy, in particular in colonic disease, thus proving a good surrogate marker for these aims. FC is useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence, for optimizing or downstage therapy. Unfortunately, FC performs less well in small bowel CD. FC is an effective fecal marker in the management of CD patients, optimizing the use of endoscopic procedures. Owing to its diagnostic accuracy, FC may represent a cornerstone of the "treat-to-target" management strategy of CD patients.
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Affiliation(s)
- Filippo Vernia
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Mirko Di Ruscio
- IBD Unit, IRCCS Ospedale Sacro Cuore - Don Calabria, Verona, Italy
| | - Gianpiero Stefanelli
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Angelo Viscido
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Giuseppe Frieri
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Giovanni Latella
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
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Martins S, Garcia D, Farinha R, Guimarães JT. Comparison of a rapid test and an automated method for faecal calprotectin measurement. Pract Lab Med 2019; 17:e00133. [PMID: 31649985 PMCID: PMC6804501 DOI: 10.1016/j.plabm.2019.e00133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 08/27/2019] [Accepted: 09/17/2019] [Indexed: 11/18/2022] Open
Affiliation(s)
- Sandra Martins
- Clinical Pathology Department, São João University Hospital Centre, Porto, Portugal
- EPIUnit, Institute of Public Health, University of Porto, Porto, Portugal
- Corresponding author. Clinical Pathology Department, São João Hospital Centre, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.
| | - David Garcia
- Clinical Pathology Department, São João University Hospital Centre, Porto, Portugal
| | - Rui Farinha
- Clinical Pathology Department, São João University Hospital Centre, Porto, Portugal
- EPIUnit, Institute of Public Health, University of Porto, Porto, Portugal
| | - João Tiago Guimarães
- Clinical Pathology Department, São João University Hospital Centre, Porto, Portugal
- EPIUnit, Institute of Public Health, University of Porto, Porto, Portugal
- Biochemistry Unit, Biomedicine Department, Faculty of Medicine, University of Porto, Porto, Portugal
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Abstract
A full understanding of the presentation and work-up of inflammatory bowel disease is necessary to ensure appropriate treatment of this complex disease. Crohn's disease and ulcerative colitis share many common clinical features but are treated very differently. This article covers the factors which contribute to IBD pathogenesis and presentation as well as the methods of diagnosis and work-up to ensure that the appropriate diagnosis is reached. This article also serves as a basis of understanding for the more complex aspects of the disease to be discussed in subsequent articles.
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Abstract
Inflammatory bowel disease (IBD) denotes a group of chronic incurable disorders characterized by relapsing-remitting inflammation of the gastrointestinal tract. IBD represents a growing global burden with a prevalence exceeding 0.3% in the Western world and an accelerating incidence in newly industrialized countries. The target for treating IBD has shifted in recent years from symptom control to mucosal healing (MH), which has been shown to be associated with favorable long-term outcomes. The gold standard for ascertaining MH is endoscopic assessment, but endoscopy is limited by its invasive nature, high cost, and finite availability. Surrogate biomarkers are therefore of great utility. Calprotectin, a cytosolic protein derived predominantly from neutrophils, is now widely used in this capacity. Calprotectin is found in various bodily fluids at concentrations proportional to the degree of inflammation, including in feces at levels roughly six times higher than in the blood. Fecal calprotectin (FCP) therefore reflects intestinal inflammation. Various assays, including point-of-care and home-based tests, are now available for measuring FCP. FCP is used for screening purposes, to aid in distinguishing inflammatory from non-inflammatory gastrointestinal conditions like irritable bowel syndrome (IBS), as well as in the monitoring of known IBD. The aims of this review are to provide an overview of the methods used to measure FCP and to review the evidence supporting the use of FCP in IBD, particularly as it pertains to screening, monitoring and predicting disease relapse.
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Affiliation(s)
- Amanda Ricciuto
- a Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children , University of Toronto , Toronto , Canada
| | - Anne M Griffiths
- a Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children , University of Toronto , Toronto , Canada
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Costa RJS, Camões-Costa V, Snipe RMJ, Dixon D, Russo I, Huschtscha Z. Impact of exercise-induced hypohydration on gastrointestinal integrity, function, symptoms, and systemic endotoxin and inflammatory profile. J Appl Physiol (1985) 2019; 126:1281-1291. [DOI: 10.1152/japplphysiol.01032.2018] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
It is commonly believed that gastrointestinal issues during exercise are exacerbated by hypohydration. This study aimed to determine the effect of exercise-induced hypohydration on gastrointestinal integrity, function, symptoms, and systemic endotoxin and inflammatory profiles. In a randomized crossover design, male endurance runners ( n = 11) performed 2 h of running at 70% of maximum oxygen uptake in 25°C ambient temperature with water provision [euhydration (EuH)] and total water restriction [hypohydration (HypoH)] during running, which accounted for 0.6 ± 0.6% and 3.1 ± 0.7% body mass loss, respectively. Blood and fecal samples were collected before and after exercise. Breath samples (H2 determination) were collected and gastrointestinal symptoms (GIS) recorded before, during, and after exercise. HypoH resulted in a higher, yet insignificant, ∆ preexercise to postexercise plasma cortisol concentration (+286 nmol/l vs. +176 nmol/l; P = 0.098) but significantly higher intestinal fatty acid-binding protein (I-FABP) (+539 pg/ml vs. +371 pg/ml; P = 0.047) concentration compared with EuH. A greater breath H2 response ( P = 0.026) was observed on HypoH (1,188 ppm/3 h, peak +12 ppm) vs. EuH (579 ppm/3 h, peak +6 ppm). Despite greater GIS incidence on HypoH (82%) vs. EuH (64%), GIS severity scores were not significant between trials. Exercise-induced leukocytosis (overall pre- to postexercise: 5.9 × 109/l to 12.1 × 109/l) was similar on both trials. Depressed in vitro neutrophil function was observed during recovery on HypoH (−36%) but not on EUH (+6%). A pre- to postexercise increase ( P < 0.05) was observed for circulating cytokine concentrations but not endotoxin values. Hypohydration during 2 h of running modestly perturbs gastrointestinal integrity and function and increases GIS incidence but does not affect systemic endotoxemia and cytokinemia. NEW & NOTEWORTHY Despite anecdotal beliefs that exercise-induced hypohydration exacerbates perturbations to gastrointestinal status, the present study reports only modest perturbations in gastrointestinal integrity, function, and symptoms compared with euhydration maintenance. Exercise-induced hypohydration does not exacerbate systemic endotoxemia and cytokinemia compared with euhydration maintenance. Programmed water intake to maintain euhydration results in gastrointestinal symptom severity similar to exercise-induced hypohydration. Maintaining euhydration during exertional stress prevents the exercise-associated depression in bacterially stimulated neutrophil function.
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Affiliation(s)
- Ricardo J. S. Costa
- Department of Nutrition, Dietetics and Food, Monash University, Notting Hill, Victoria, Australia
| | - Vera Camões-Costa
- Department of Nutrition, Dietetics and Food, Monash University, Notting Hill, Victoria, Australia
- The Health & Aging Research Group, Swinburne University of Technology, Melbourne, Victoria, Australia
| | - Rhiannon M. J. Snipe
- Centre for Sport Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia
| | - David Dixon
- Writtle University College, Chelmsford, United Kingdom
| | - Isabella Russo
- Department of Nutrition, Dietetics and Food, Monash University, Notting Hill, Victoria, Australia
| | - Zoya Huschtscha
- Department of Nutrition, Dietetics and Food, Monash University, Notting Hill, Victoria, Australia
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34
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Ma C, Battat R, Parker CE, Khanna R, Jairath V, Feagan BG. Update on C-reactive protein and fecal calprotectin: are they accurate measures of disease activity in Crohn's disease? Expert Rev Gastroenterol Hepatol 2019; 13:319-330. [PMID: 30791776 DOI: 10.1080/17474124.2019.1563481] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
'Treat-to-target' paradigms in Crohn's disease (CD) directed at suppressing intestinal inflammation require accurate and reliable measures of disease activity. Although endoscopy has traditionally been considered a gold standard, cost, complexity, resource limitations, and invasiveness are important limitations. Hence, substantial interest exists for non-invasive serum and fecal biomarkers, namely C-reactive protein (CRP) and fecal calprotectin (FC), in the diagnosis, monitoring, and treatment of CD. Areas covered: We review the evidence for using serum CRP and FC in distinguishing patients with CD from those with irritable bowel syndrome, categorizing disease activity among patients with an established diagnosis of CD, predicting the likelihood of treatment response, identifying asymptomatic patients in medically or surgically induced remission who are at risk for disease relapse, and as treatment targets. Expert commentary: Accurate interpretation of CRP and FC is dependent on several factors including the clinical context, the performance characteristics of the assay, the specified test cut-offs, and the pre-test probability of disease. Emerging evidence indicates that CRP and FC are valuable adjuncts for the management of CD in specific circumstances described in this review.
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Affiliation(s)
- Christopher Ma
- a Division of Gastroenterology and Hepatology , University of Calgary , Calgary , Alberta , Canada.,b Robarts Clinical Trials Inc ., London , Ontario , Canada
| | - Robert Battat
- b Robarts Clinical Trials Inc ., London , Ontario , Canada.,c Division of Gastroenterology , University of California San Diego , La Jolla , CA , USA
| | | | - Reena Khanna
- d Department of Medicine , Western University , London , Ontario , Canada
| | - Vipul Jairath
- b Robarts Clinical Trials Inc ., London , Ontario , Canada.,d Department of Medicine , Western University , London , Ontario , Canada.,e Department of Epidemiology and Biostatistics , Western University , London , Ontario , Canada
| | - Brian Gordon Feagan
- b Robarts Clinical Trials Inc ., London , Ontario , Canada.,d Department of Medicine , Western University , London , Ontario , Canada.,e Department of Epidemiology and Biostatistics , Western University , London , Ontario , Canada
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Fiorino G, Allocca M, Chaparro M, Coenen S, Fidalgo C, Younge L, Gisbert JP. 'Quality of Care' Standards in Inflammatory Bowel Disease: A Systematic Review. J Crohns Colitis 2019; 13:127-137. [PMID: 30423033 DOI: 10.1093/ecco-jcc/jjy140] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Inflammatory bowel disease [IBD] includes chronic, disabling and progressive conditions that need a complex approach and management. Although several attempts have been made to standardize the care of IBD patients, no clear definitions of a global 'standard of care' are currently available. METHODS We performed a systematic review of the available literature, searching for all relevant data concerning three main domains of standards of quality of care in IBD patients: structure, process and outcomes. From the literature search, 2394 abstracts were retrieved, and 62 relevant papers were included in the final review. RESULTS Standards of quality of care in IBD include several aspects that can be summarized in three identified domains: structure, process and outcomes. The suggested structure of an IBD Unit includes a multi-disciplinary approach, effective referral processes, improved access using helplines, and departmental guidelines/pathways with identification of measurable quality indicators. Coordinated care models which incorporate a multi-disciplinary approach, structured clinical pathways or processes for the diagnosis, monitoring and treatment of IBD, fast-track recovery from IBD surgery, designated IBD clinics, virtual clinics and telemanagement are currently considered the main standards for process, although supporting data are limited. Several consensus statements on outcomes and quality indicators have been reported, focusing on outcomes in symptoms, function and quality of life restoration, survival and disease control, in addition to effective healthcare utilization. CONCLUSIONS The results of this systematic review can provide the basis for general recommendations for standards of quality of care in IBD.
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Affiliation(s)
- Gionata Fiorino
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy
| | - Mariangela Allocca
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy
| | - Maria Chaparro
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Sofie Coenen
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Catarina Fidalgo
- Gastroenterology Division, Hospital Beatriz Ângelo, Loures, Portugal
| | - Lisa Younge
- Barts Health - Royal London Hospital, London, UK
| | - Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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36
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Allocca M, Fiorino G, Bonovas S, Furfaro F, Gilardi D, Argollo M, Magnoni P, Peyrin-Biroulet L, Danese S. Accuracy of Humanitas Ultrasound Criteria in Assessing Disease Activity and Severity in Ulcerative Colitis: A Prospective Study. J Crohns Colitis 2018; 12:1385-1391. [PMID: 30085066 PMCID: PMC6260119 DOI: 10.1093/ecco-jcc/jjy107] [Citation(s) in RCA: 107] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Colonoscopy [CS] is the standard for assessing disease activity in ulcerative colitis [UC], although invasive and poorly tolerated. Bowel ultrasound [BUS] may be a valid alternative in UC patients; however, the comparative accuracy between BUS and CS is unknown. METHODS Consecutive patients with UC were prospectively assessed by CS and BUS. Colonic wall thickening [CWT >3 mm], colonic wall flow at power Doppler [CWF], colonic wall pattern [CWP], and presence of lymph nodes evaluated at BUS were compared with CS. The endoscopic activity was assessed according to the Mayo endoscopic sub-score [0-3]. All BUS investigations were performed by two independent gastroenterologists and the kappa statistic for agreement was calculated. Ultrasonography-based criteria (Humanitas Ultrasound Criteria [HUC]) were developed. RESULTS A total of 53 UC patients [56% with left-sided colitis, 19% with pancolitis] were prospectively enrolled. Of these, 22 patients had mucosal healing [Mayo endoscopic sub-score 0-1] and 31 patients were in endoscopic activity. CWT, CWF, hypoechogenic CWP and the presence of lymph nodes significantly correlated with endoscopic activity [p < 0.05]. CWT [p = 0.01] and CWF [p = 0.09] were independent predictors for endoscopic activity. The HUC developed are: [i] the presence of a CWF and CWT > 3 mm; or [ii] the absence of a CWF and CWT > 4.43 mm. They showed high accuracy for the detection of disease activity [sensitivity 0.71, specificity 1.00]. The interobserver agreement for BUS was excellent [kappa 0.86]. CONCLUSIONS BUS is a non-invasive, easy-to-use tool to manage UC patients in clinical practice. HUC were very accurate in assessing disease activity in UC patients.
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Affiliation(s)
- Mariangela Allocca
- IBD Centre, Humanitas Clinical and Research Centre, Rozzano, Milan, Italy,Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy
| | - Gionata Fiorino
- IBD Centre, Humanitas Clinical and Research Centre, Rozzano, Milan, Italy,Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy
| | - Stefanos Bonovas
- IBD Centre, Humanitas Clinical and Research Centre, Rozzano, Milan, Italy,Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy
| | - Federica Furfaro
- IBD Centre, Humanitas Clinical and Research Centre, Rozzano, Milan, Italy
| | - Daniela Gilardi
- IBD Centre, Humanitas Clinical and Research Centre, Rozzano, Milan, Italy
| | - Marjorie Argollo
- Department of Gastroenterology, Universidade Federal de São Paulo UNIFESP, São Paulo, Brazil
| | - Paola Magnoni
- Service of Echography, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm U954, University Hospital of Nancy, Lorraine University, Nancy, France
| | - Silvio Danese
- IBD Centre, Humanitas Clinical and Research Centre, Rozzano, Milan, Italy,Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy,Corresponding author: Silvio Danese, MD, PhD, Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, 20089, Rozzano, Milan, Italy. Tel.: +390282244771; Fax: +39028224259;
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Nakamura S, Imaeda H, Nishikawa H, Iimuro M, Matsuura M, Oka H, Oku J, Miyazaki T, Honda H, Watanabe K, Nakase H, Andoh A. Usefulness of fecal calprotectin by monoclonal antibody testing in adult Japanese with inflammatory bowel diseases: a prospective multicenter study. Intest Res 2018; 16:554-562. [PMID: 30301337 PMCID: PMC6223455 DOI: 10.5217/ir.2018.00027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2018] [Accepted: 05/21/2018] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Noninvasive objective monitoring is advantageous for optimizing treatment strategies in patients inflammatory bowel disease (IBD). Fecal calprotectin (FCP) is superior to traditional biomarkers in terms of assessing the activity in patients with IBD. However, there are the differences among several FCP assays in the dynamics of FCP. In this prospective multicenter trial, we investigated the usefulness of FCP measurements in adult Japanese patients with IBD by reliable enzyme immunoassay using a monoclonal antibody. Methods We assessed the relationship between FCP levels and disease or endoscopic activity in patients with ulcerative colitis (UC, n=64) or Crohn’s disease (CD, n=46) compared with healthy controls (HCs, n=64). Results FCP levels in UC patients strongly correlated with the Disease Activity Index (rs=0.676, P<0.0001) and Mayo endoscopic subscore (MES; rs=0.677, P<0.0001). FCP levels were significantly higher even in patients with inactive UC or CD compared with HCs (P=0.0068, P<0.0001). The optimal cutoff value between MES 1 and 2 exhibited higher sensitivity (94.1%). FCP levels were significantly higher in active UC patients than in inactive patients (P<0.001), except those with proctitis. The Crohn’s Disease Activity Index tended to correlate with the FCP level (rs=0.283, P=0.0565). Conclusions Our testing method using a monoclonal antibody for FCP was well-validated and differentiated IBD patients from HCs. FCP may be a useful biomarker for objective assessment of disease activity in adult Japanese IBD patients, especially those with UC.
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Affiliation(s)
- Shiro Nakamura
- Division of Internal Medicine, Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Nishinomiya, Japan
| | - Hirotsugu Imaeda
- Department of Medicine, Shiga University of Medical Science, Otsu, Japan
| | - Hiroki Nishikawa
- Center for Clinical Research and Education, Hyogo College of Medicine, Nishinomiya, Japan
| | - Masaki Iimuro
- Division of Internal Medicine, Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Nishinomiya, Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Hideo Oka
- Division of Gastroenterology and Hepatology, Amagasaki Central Hospital, Amagasaki, Japan
| | - Junsuke Oku
- Division of Gastroenterology and Hepatology, Amagasaki Central Hospital, Amagasaki, Japan.,Oku Clinic, Higashiosaka, Japan
| | - Takako Miyazaki
- Division of Internal Medicine, Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Nishinomiya, Japan.,Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | | | - Kenji Watanabe
- Division of Internal Medicine, Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Nishinomiya, Japan.,Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Graduate School of Medicine Kyoto University, Kyoto, Japan.,Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Akira Andoh
- Department of Medicine, Shiga University of Medical Science, Otsu, Japan
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Khanna R, Narula N, Feagan BG. The Role of Biomarkers in Clinical Trials of Inflammatory Bowel Disease. Inflamm Bowel Dis 2018; 24:1619-1623. [PMID: 29846593 DOI: 10.1093/ibd/izy195] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Indexed: 12/15/2022]
Abstract
Clinical trials require valid outcome measures to assess the therapeutic benefit of investigational agents. Recently, regulatory authorities have mandated the use of patient-reported outcomes in combination with an objective measure of disease activity as primary outcome measures in inflammatory bowel disease trials. Endoscopy has commonly fulfilled the latter role; however, due to the costs and complexity of these assessments, interest has emerged in the use of noninvasive biomarkers. The role of C-reactive protein, fecal calprotectin, and fecal lactoferrin in clinical research is discussed.
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Affiliation(s)
- Reena Khanna
- Department of Medicine, Division of Gastroenterology, University of Western Ontario, London, Ontario, Canada
| | - Neeraj Narula
- Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
| | - Brian G Feagan
- Department of Medicine, Division of Gastroenterology, University of Western Ontario, London, Ontario, Canada.,Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
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Symptoms Do Not Correlate With Findings From Colonoscopy in Children With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis. Clin Gastroenterol Hepatol 2018; 16:1098-1105.e1. [PMID: 29378308 DOI: 10.1016/j.cgh.2018.01.020] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Revised: 01/09/2018] [Accepted: 01/12/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Approximately 75% of children with primary sclerosing cholangitis (PSC) also have inflammatory bowel disease (IBD). IBD in patients with PSC (PSC-IBD) often has a unique phenotype, including a mild clinical course, yet it is associated with an increased risk of colorectal cancer compared with colonic IBD without PSC. We investigated whether subclinical endoscopic and histologic inflammation could account for the increased risk of colorectal cancer in patients with PSC-IBD, and whether these patients have increased fecal levels of calprotectin, a marker of inflammation. METHODS We performed a prospective study of children (age, <18 y) with colonic IBD with and without PSC who underwent colonoscopy from February 1, 2016, through March 31, 2017, at the Hospital for Sick Children in Toronto, Canada. We collected pediatric ulcerative colitis activity index (PUCAI) scores (to measure symptoms) and fecal levels of calprotectin from 37 children with PSC-IBD and 50 children with only IBD (controls; UC or IBD-unclassified). Colonoscopies were scored using the Mayo endoscopic subscore and the UC Endoscopic Index of Severity (UCEIS) scores, and histologic activity was graded. Among patients in clinical remission, endoscopic scores and the odds of active endoscopic disease (based on a UCEIS score ≥1) were compared between patients with and without PSC in univariate and multivariable analyses. Correlations between activity markers were compared between groups. The ability of fecal calprotectin to identify mucosal healing in patients with PSC-IBD was assessed using receiver operating characteristic curve analyses. Analogous analyses were performed for histologic activity. RESULTS Patients with PSC-IBD in clinical remission had higher endoscopic scores and greater odds of active endoscopic disease than controls (odds ratio, 5.9; 95% CI, 1.6-21.5). There was a higher degree of correlation between PUCAI and UCEIS scores in controls (r = 0.82) than in patients with PSC-IBD (r = 0.51; P = .01). Fecal levels of calprotectin correlated with UCEIS in patients with PSC-IBD (r = 0.84) and controls (r = 0.82; P = .80). Fecal levels of calprotectin identified mucosal healing in patients with PSC-IBD with an area under the receiver operating characteristic curve of 0.94 (optimal cut-point, 93 μg/g; 100% sensitivity and 92% specificity). Histologic activity scores and the odds of active histologic disease were also greater in patients in clinical remission with PSC-IBD than controls. CONCLUSIONS Children with PSC-IBD in clinical remission, based on PUCAI scores, have a significantly higher risk of active endoscopic and histologic disease than children with colitis without PSC. Fecal levels of calprotectin correlate with endoscopic findings in pediatric patients with PSC-IBD; levels below 93 μg/g are associated with mucosal healing.
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40
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Dai C, Jiang M, Sun MJ, Cao Q. Fecal immunochemical test for predicting mucosal healing in ulcerative colitis patients: A systematic review and meta-analysis. J Gastroenterol Hepatol 2018; 33:990-997. [PMID: 29427297 DOI: 10.1111/jgh.14121] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Revised: 01/16/2018] [Accepted: 01/31/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIM Fecal immunochemical test (FIT) is a promising marker for assessment of inflammatory bowel disease activity. However, the utility of FIT for predicting mucosal healing (MH) of ulcerative colitis (UC) patients has yet to be clearly demonstrated. The objective of our study was to perform a diagnostic test accuracy test meta-analysis evaluating the diagnostic accuracy of FIT in predicting MH of UC patients. METHODS We systematically searched the databases from inception to November 2017 that evaluated MH in UC. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. The extracted data were pooled using a summary receiver operating characteristic curve model. Random-effects model was used to summarize the diagnostic odds ratio, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. RESULTS Six studies comprising 625 UC patients were included in the meta-analysis. The pooled sensitivity and specificity values for predicting MH in UC were 0.77 (95% confidence interval [CI], 0.72-0.81) and 0.81 (95% CI, 0.76-0.85), respectively. The FIT level had a high rule-in value (positive likelihood ratio, 3.79; 95% CI, 2.85-5.03) and a moderate rule-out value (negative likelihood ratio, 0.26; 95% CI, 0.16-0.43) for predicting MH in UC. The results of the receiver operating characteristic curve analysis (area under the curve, 0.88; standard error of the mean, 0.02) and diagnostic odds ratio (18.08; 95% CI, 9.57-34.13) also revealed improved discrimination for identifying MH in UC with FIT concentration. CONCLUSION Our meta-analysis has found that FIT is a simple, reliable non-invasive marker for predicting MH in UC patients.
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Affiliation(s)
- Cong Dai
- Department of Gastroenterology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China
| | - Min Jiang
- Department of Gastroenterology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China
| | - Ming-Jun Sun
- Department of Gastroenterology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China
| | - Qin Cao
- Department of Gastroenterology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China
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Kammerlander H, Nielsen J, Kjeldsen J, Knudsen T, Gradel KO, Friedman S, Nørgård BM. Fecal Calprotectin During Pregnancy in Women With Moderate-Severe Inflammatory Bowel Disease. Inflamm Bowel Dis 2018; 24:839-848. [PMID: 29506137 DOI: 10.1093/ibd/izx055] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Fecal calprotectin (FC) is a biomarker used for assessing disease activity among IBD patients. Sparse knowledge exists as to whether FC correlates with clinical disease activity during pregnancy. Our aim was to assess FC and selected biomarkers in women with moderate-severe IBD and correlate them with clinical disease activity scores in pregnant women. METHODS We identified a nationwide cohort of 219 singleton pregnancies in women with moderate-severe disease (all treated with anti-tumor recrosis factor-α [anti-TNF-α] therapy during pregnancy), and we reviewed the medical records to extract clinical details and information on biomarkers. FC, C-reactive protein (CRP), hemoglobin, and albumin were collected according to each trimester. RESULTS A total of 346 FC measurements were obtained throughout the gestational periods. FC values were between 80-120, 259-349, and 778-1277 mg/kg in women with clinically inactive, mild, and moderate-severe disease activity, respectively, and were significantly higher among the women with clinical disease activity. ROC curves for disease activity were computed according to the preconception period: 0.81 (95% confidence interval [CI], 0.69-0.93), first trimester: 0.73 (95% CI, 0.60-0.86), second trimester: 0.74 (95% CI, 0.62-0.86), and third trimester: 0.76 (95% CI, 0.64-0.88), respectively. We found a sensitivity of 69.7%-80.0%, a specificity of 66.7%-73.3%, and a positive predictive value of 66.7%-74.4% over the 4 gestational periods when a cutoff of 200 mg/kg was used. We found no clinically significant differences in CRP, albumin, or hemoglobin. CONCLUSIONS FC in pregnant women with moderate-severe IBD treated with anti-TNF-α therapy was significantly higher in women with clinical disease activity compared with the women without. FC correlated with the level of clinical disease activity in all gestational periods.
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Affiliation(s)
- Heidi Kammerlander
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Jan Nielsen
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Jens Kjeldsen
- Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark
| | - Torben Knudsen
- Department of Medical Gastroenterology, Hospital of Southwest Jutland, Esbjerg, Denmark
| | - Kim Oren Gradel
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Sonia Friedman
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.,Crohn's and Colitis Center, Brigham and Women's Hospital, Boston, Massachusetts and Harvard Medical School, Boston, Massachusetts
| | - Bente Mertz Nørgård
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.,Crohn's and Colitis Center, Brigham and Women's Hospital, Boston, Massachusetts and Harvard Medical School, Boston, Massachusetts
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Within-Stool and Within-Day Sample Variability of Fecal Calprotectin in Patients With Inflammatory Bowel Disease: A Prospective Observational Study. J Clin Gastroenterol 2018; 52:235-240. [PMID: 28009684 DOI: 10.1097/mcg.0000000000000776] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND GOALS The use of fecal calprotectin (FC) as a stool biomarker for differentiating inflammatory bowel disease (IBD) from IBS has been well validated, and there is a strong correlation between FC and the presence of endoscopic inflammatory lesions. However, recent studies have demonstrated intraindividual sample variability in patients with IBD, possibly limiting the reliability of using a single sample for monitoring disease activity. Our aim was to assess the within-stool and within-day sample variability of FC concentrations in patients with IBD. STUDY We examined a cross-sectional cohort of 50 adult IBD patients. Eligible patients were instructed to collect 3 samples from different parts of the stool from their first bowel movement of the day and 3 samples from each of up to 2 additional bowel movements within 24 hours. FC concentrations were measured by a rapid, quantitative point-of-care test using lateral flow technology (Quantum Blue). Descriptive statistics were used to assess FC variability within a single bowel movement and between different movements at different FC positivity cutoffs. RESULTS Within a single bowel movement, there was clinically significant sample variability ranging from 8% to 23% depending on the time of the day or on the FC positivity cutoff value. Between bowel movements, there was clinically significant sample variability ranging from 13% to 26% depending on the FC positivity cutoff. CONCLUSIONS Considering a single FC sample, the first sample of the day with an FC positivity cutoff of 250 μg/g provided the most reliable indication of disease activity.
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Snipe RMJ, Khoo A, Kitic CM, Gibson PR, Costa RJS. The impact of exertional-heat stress on gastrointestinal integrity, gastrointestinal symptoms, systemic endotoxin and cytokine profile. Eur J Appl Physiol 2017; 118:389-400. [DOI: 10.1007/s00421-017-3781-z] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Accepted: 12/03/2017] [Indexed: 02/07/2023]
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Noninvasive Fecal Immunochemical Testing and Fecal Calprotectin Predict Mucosal Healing in Inflammatory Bowel Disease: A Prospective Cohort Study. Inflamm Bowel Dis 2017. [PMID: 28644184 DOI: 10.1097/mib.0000000000001173] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND The noninvasive biomarkers fecal immunochemical testing (FIT) and fecal calprotectin (FCP) are sensitive for prediction of mucosal inflammation in inflammatory bowel disease. However, neither test has yet been shown to independently and accurately predict mucosal healing (MH). We aimed to assess the specificity of noninvasive FIT and FCP for MH prediction. METHODS In this prospective cohort study of adult inflammatory bowel disease outpatients presenting for colonoscopy, stool samples for FIT and FCP were collected 48 hours before endoscopy. Using MH defined by Simple Endoscopic Score for Crohn's disease (SES-CD = 0), Rutgeert's score (i0), and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS = 3), receiver operator characteristic curves were plotted, and sensitivity, specificity, positive and negative predictive values, and areas under the curve were calculated. Multivariate logistic regression analysis was used to develop a clinical model for noninvasively predicting MH. RESULTS Eighty patients (40 Crohn's disease and 40 ulcerative colitis) were enrolled. The specificities of FIT <100 ng/mL and FCP <250 μg/g for MH were 0.57 (95% confidence interval, 0.38-0.74) and 0.77 (0.57-0.89), respectively. Positive predictive values for MH for FIT <100 ng/mL and FCP <250 μg/g were 0.78 (0.64-0.87) and 0.77 (0.58-0.90), respectively. In multivariate modeling, combining FIT, FCP, and clinical symptomatic remission improved specificity for MH to 0.90 (0.72-0.97) with positive predictive values of 0.84 (0.60-0.96). Areas under the curve for FIT was higher for patients with ulcerative colitis (0.88) than for patients with Crohn's disease (0.69, P = 0.05). CONCLUSIONS FIT and FCP have similar performance characteristics for identifying MH. Combined, low FIT, low FCP, and clinical remission are specific for MH.
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Ananthakrishnan AN, Donaldson T, Lasch K, Yajnik V. Management of Inflammatory Bowel Disease in the Elderly Patient: Challenges and Opportunities. Inflamm Bowel Dis 2017; 23:882-893. [PMID: 28375885 PMCID: PMC5687915 DOI: 10.1097/mib.0000000000001099] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The population of older patients with inflammatory bowel disease (IBD) continues to grow, partly reflecting the aging global population in general. The debilitating effects of IBD compound age-related decrements in health and functional capacity, and make the medical management of older patients with Crohn's disease and ulcerative colitis distinctly challenging to clinicians. Here, we review the recent literature describing the pharmacologic management of IBD in this population, with focus on the safety, tolerability, and efficacy of common treatment options, such as steroids, immunomodulators, tumor necrosis factor-α antagonists, and integrin antagonists; surgical interventions in older patients are also discussed. Few studies have systematically and prospectively evaluated the clinical challenges in the medical management of IBD in this patient population, leaving a limited evidence base to which clinicians can turn to for guidance. Treatment patterns may thus be suboptimal. For example, prolonged steroid use in the elderly was found to be common, causing significant morbidity from side effects in a particularly vulnerable population. Finally, within the context of a limited evidence base, we discuss common treatment scenarios to define the parameters within which physicians can individualize care for older patients with IBD. Overall, older patients with IBD are at higher risk of adverse events and less treatment responsiveness compared with younger patients, underscoring the need for future studies to fully characterize appropriate treatment courses for this population.
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Affiliation(s)
| | | | - Karen Lasch
- Takeda Pharmaceuticals USA, Inc., Deerfield, IL, USA
| | - Vijay Yajnik
- Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Sánchez-Martínez M, Garcia-Planella E, Laiz A, Puig L. Enfermedad inflamatoria intestinal: abordaje conjunto digestivo-dermatológico. ACTAS DERMO-SIFILIOGRAFICAS 2017; 108:184-191. [DOI: 10.1016/j.ad.2016.07.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Revised: 07/01/2016] [Accepted: 07/10/2016] [Indexed: 01/05/2023] Open
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Inflammatory Bowel Disease: Joint Management in Gastroenterology and Dermatology. ACTAS DERMO-SIFILIOGRAFICAS 2017. [DOI: 10.1016/j.adengl.2017.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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Ambe PC, Orth V, Gödde D, Zirngibl H. Improving the Preoperative Diagnostic Accuracy of Acute Appendicitis. Can Fecal Calprotectin Be Helpful? PLoS One 2016; 11:e0168769. [PMID: 28033410 PMCID: PMC5199045 DOI: 10.1371/journal.pone.0168769] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Accepted: 12/06/2016] [Indexed: 12/13/2022] Open
Abstract
Background Is the patient really suffering from acute appendicitis? Right lower quadrant pain is the most common sign of acute appendicitis. However, many other bowels pathologies might mimic acute appendicitis. Due to fear of the consequences of delayed or missed diagnosis, the indication for emergency appendectomy is liberally made. This has been shown to be associated with high rates of negative appendectomy with risk of potentially serious or lethal complications. Thus there is need for a better preoperative screening of patients with suspected appendicitis. Methods This prospective single center single-blinded pilot study was conducted in the Department of surgery at the HELIOS Universitätsklinikum Wuppertal, Germany. Calprotectin was measured in pre-therapeutic stool samples of patients presenting in the emergency department with pain to the right lower quadrant. Fecal calprotectin (FC) values were analyzed using commercially available ELISA kits. Cut-off values for FC were studied using the receiver-operator characteristic (ROC) curve. The Area under the curve (AUC) was reported for each ROC curve. Results The mean FC value was 51.4 ± 118.8 μg/g in patients with AA, 320.9 ± 416.6 μg/g in patients with infectious enteritis and 24.8 ± 27.4 μg/g in the control group. ROC curve showed a close to 80% specificity and sensitivity of FC for AA at a cut-off value of 51 μg/g, AUC = 0.7. The sensitivity of FC at this cut-off value is zero for enteritis with a specificity of 35%. Conclusion Fecal calprotectin could be helpful in screening patients with pain to the right lower quadrant for the presence of acute appendicitis or infectious enteritis with the aim of facilitating clinical decision-making and reducing the rate of negative appendectomy.
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Affiliation(s)
- Peter C. Ambe
- Department of Surgery HELIOS Universitätsklinikum Wuppertal Witten–Herdecke University Heusnerstr. Wuppertal, Germany
- * E-mail:
| | - Valerie Orth
- Department of Surgery HELIOS Universitätsklinikum Wuppertal Witten–Herdecke University Heusnerstr. Wuppertal, Germany
| | - Daniel Gödde
- Institute of Pathology and Molecular Pathology HELIOS Universitätsklinikum Wuppertal Witten–Herdecke University Heusnerstr. Wuppertal, Germany
| | - Hubert Zirngibl
- Department of Surgery HELIOS Universitätsklinikum Wuppertal Witten–Herdecke University Heusnerstr. Wuppertal, Germany
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Mitchell RA, Shuster C, Shahidi N, Galorport C, DeMarco ML, Rosenfeld G, Enns RA, Bressler B. The Utility of Infliximab Therapeutic Drug Monitoring among Patients with Inflammatory Bowel Disease and Concerns for Loss of Response: A Retrospective Analysis of a Real-World Experience. Can J Gastroenterol Hepatol 2016; 2016:5203898. [PMID: 27957480 PMCID: PMC5121455 DOI: 10.1155/2016/5203898] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Revised: 09/24/2016] [Accepted: 10/19/2016] [Indexed: 12/29/2022] Open
Abstract
Background. Infliximab (IFX) therapeutic drug monitoring (TDM) allows for objective decision making in patients with inflammatory bowel disease (IBD) and loss of response. Questions remain about whether IFX TDM improves outcomes. Methods. Patients with IBD who had IFX TDM due to concerns for loss of response were considered for inclusion. Serum IFX trough concentration and anti-drug antibody (ADA) concentrations were measured. Patients were grouped by TDM results: group 1, low IFX/high ADA; group 2, low IFX/low ADA; group 3, therapeutic IFX. Changes in management were analyzed according to groupings; remission rates were assessed at 6 months. Results. 71 patients were included of whom 37% underwent an appropriate change in therapy. Groups 1 (67%) and 2 (83%) had high adherence compared to only 9% in group 3. At 6 months, 57% had achieved remission. More patients who underwent an appropriate change in therapy achieved remission, though this did not reach statistical significance (69% versus 49%; P = 0.098). Conclusions. A trend towards increased remission rates was associated with appropriate changes in management following TDM results. Many patients with therapeutic IFX concentrations did not undergo an appropriate change in management, potentially reflecting a lack of available out-of-class options at the time of TDM or due to uncertainty of the meaning of the reported therapeutic range.
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Affiliation(s)
- Robert A. Mitchell
- St. Paul's Hospital, Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada
| | - Constantin Shuster
- St. Paul's Hospital, Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada
| | - Neal Shahidi
- St. Paul's Hospital, Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada
| | - Cherry Galorport
- St. Paul's Hospital, Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada
| | - Mari L. DeMarco
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Gregory Rosenfeld
- St. Paul's Hospital, Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada
| | - Robert A. Enns
- St. Paul's Hospital, Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada
| | - Brian Bressler
- St. Paul's Hospital, Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada
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Rosenfeld G, Greenup AJ, Round A, Takach O, Halparin L, Saadeddin A, Ho JK, Lee T, Enns R, Bressler B. FOCUS: Future of fecal calprotectin utility study in inflammatory bowel disease. World J Gastroenterol 2016; 22:8211-8218. [PMID: 27688663 PMCID: PMC5037090 DOI: 10.3748/wjg.v22.i36.8211] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Revised: 07/24/2016] [Accepted: 08/23/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the perspective of gastroenterologists regarding the impact of fecal calprotectin (FC) on the management of patients with inflammatory bowel disease (IBD).
METHODS Patients with known IBD or symptoms suggestive of IBD for whom the physician identified that FC would be clinically useful were recruited. Physicians completed an online “pre survey” outlining their rationale for the test. After receipt of the test results, the physicians completed an online “post survey” to portray their perceived impact of the test result on patient management. Clinical outcomes for a subset of patients with follow-up data available beyond the completion of the “post survey” were collected and analyzed.
RESULTS Of 373 test kits distributed, 290 were returned, resulting in 279 fully completed surveys. One hundred and ninety patients were known to have IBD; 147 (77%) with Crohn’s Disease, 43 (21%) Ulcerative Colitis and 5 (2%) IBD unclassified. Indications for FC testing included: 90 (32.2%) to differentiate a new diagnosis of IBD from Irritable Bowel Syndrome (IBS), 85 (30.5%) to distinguish symptoms of IBS from IBD in those known to have IBD and 104 (37.2%) as an objective measure of inflammation. FC levels resulted in a change in management 51.3% (143/279) of the time which included a significant reduction in the number of colonoscopies (118) performed (P < 0.001). Overall, 97.5% (272/279) of the time, the physicians found the test sufficiently useful that they would order it again in similar situations. Follow-up data was available for 172 patients with further support for the clinical utility of FC provided.
CONCLUSION The FC test effected a change in management 51.3% of the time and receipt of the result was associated with a reduction in the number of colonoscopies performed.
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