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Vibhishanan S, Oka P, Zammit S, Sidhu R. Elevated fecal calprotectin: Does capsule endoscopy have a role in the diagnostic algorithm? REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2025:S2255-534X(25)00011-8. [PMID: 40251054 DOI: 10.1016/j.rgmxen.2024.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 06/02/2024] [Indexed: 04/20/2025]
Abstract
INTRODUCTION The purpose of this study was to examine the utility of small bowel capsule endoscopy (SBCE) in the diagnostic pathway of patients that had elevated fecal calprotectin (FC) and normal colonoscopy. METHODS Patients with elevated FC and normal colonoscopy that underwent SBCE in the last 4 years were included. Patients were divided into 3 groups: group 1: patients with isolated small bowel Crohn's disease (SBCD) on SBCE; group 2: patients with elevated FC but normal SBCE; and group 3: patients with isolated terminal ileitis. RESULTS The study included 320 patients (group 1: 254 patients, group 2: 50 patients, and group 3: 16 patients). The median age was 42.5 years (IQR 26) across the three groups and 52.4% of the patients had a new diagnosis of SBCD. In group 1, active disease was identified distally in 247 patients (77.2%), proximal involvement in 90 patients (28.1%), and extensive SBCD in 68 patients (21.3%). Magnetic resonance enterography (MRE) was carried out in 229 (90.1%) patients in group 1 and was negative in 42 patients with SBCD. The diagnostic yield of SBCE was higher than that of MRE (p < 0.0001). In group 2, the final diagnoses included Helicobacter pylori infection (n = 2), NSAID use (n = 3), celiac disease (n = 2), and microscopic colitis (n = 1). The final diagnoses in group 3 were idiopathic terminal ileitis (n = 11), inflammatory bowel disease (n = 3), and infective terminal ileitis (n = 2). CONCLUSION SBCE influences the patient pathway even when negative/normal. It is better at identifying early SBCD, when compared with MRE.
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Affiliation(s)
- S Vibhishanan
- Unidad Académica de Gastroenterología, Hospitales Educativos de Sheffield, Sheffield, United Kingdom; División de Medicina Clínica, Facultad de Medicina y Salud Poblacional, Universidad de Sheffield, Sheffield, United Kingdom
| | - P Oka
- Unidad Académica de Gastroenterología, Hospitales Educativos de Sheffield, Sheffield, United Kingdom; División de Medicina Clínica, Facultad de Medicina y Salud Poblacional, Universidad de Sheffield, Sheffield, United Kingdom.
| | - S Zammit
- Departamento de Gastroenterología, Hospital mater Dei, Msida, Malta
| | - R Sidhu
- Unidad Académica de Gastroenterología, Hospitales Educativos de Sheffield, Sheffield, United Kingdom; División de Medicina Clínica, Facultad de Medicina y Salud Poblacional, Universidad de Sheffield, Sheffield, United Kingdom
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Cosier D, Lambert K, Charlton K, Batterham M, Little RD, Wu N, Tavakoli P, Ghaly S, Pipicella JL, Connor S, Leach S, Lemberg DA, Houshyar Y, Jayawardana T, Koentgen S, Hold GL. Dietary Patterns and Fibre Intake Are Associated with Disease Activity in Australian Adults with Inflammatory Bowel Disease: An Exploratory Dietary Pattern Analysis. Nutrients 2024; 16:4349. [PMID: 39770970 PMCID: PMC11677955 DOI: 10.3390/nu16244349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 12/10/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Few studies have explored the relationship between habitual dietary patterns and disease activity in people with Inflammatory Bowel Disease (IBD). This cross-sectional study explored the association between dietary patterns and clinical and objective markers of inflammation in adults from the Australian IBD Microbiome Study. METHODS Dietary patterns were derived using principal component analysis (PCA) of baseline food frequency questionnaire data. Food intake was quantified using 3-day food record data. Associations between dietary intake and both clinical disease activity index (CDAI) and faecal calprotectin (FCP) were analysed. RESULTS Participants included 412 adults (IBD = 223, Healthy controls (HC) = 189). Both cohorts consumed poor-quality diets with inadequate servings of most food groups compared to Australian reference standards. IBD participants without FCP inflammation had significantly higher fibre intake than those with moderate FCP. In the Crohn's Disease group, high adherence to 'High plant diversity' and 'Meat eaters' dietary patterns were associated with increased CDAI and FCP, respectively. In the combined IBD cohort, high adherence to a 'Vegan-style' dietary pattern was associated with increased FCP. CONCLUSIONS There is a need for dietary modifications among Australian adults, both with and without IBD, to improve dietary fibre intake and adherence to dietary guidelines. Dietary patterns characterised by a high intake of plant foods or meat products were both positively associated with indicators of active IBD. It is possible that some participants with active IBD were modifying their diet to try to manage their disease and reduce symptoms, contributing to the association between healthier dietary patterns and active disease. Further clinical and longitudinal studies are needed to expand upon the findings. This study offers a unique contribution by utilising FCP as an objective marker of intestinal inflammation and applying dietary pattern analysis to investigate the relationship between diet and inflammatory markers.
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Affiliation(s)
- Denelle Cosier
- School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Kelly Lambert
- School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Karen Charlton
- School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Marijka Batterham
- Statistical Consulting Centre, National Institute for Applied Statistical Research Australia, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Robert D. Little
- Department of Gastroenterology, Alfred Health, Melbourne, VIC 3004, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3800, Australia
| | - Nan Wu
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
- Department of Gastroenterology, Sutherland Hospital, Sydney, NSW 2229, Australia
| | - Paris Tavakoli
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Simon Ghaly
- Department of Gastroenterology and Hepatology, St Vincent’s Hospital Sydney and St Vincent’s Clinical School, UNSW Medicine & Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Joseph L. Pipicella
- Department of Gastroenterology, Liverpool Hospital and South West Sydney Clinical Campuses, UNSW Medicine & Health, University of New South Wales, Sydney, NSW 2033, Australia
- Crohn’s Colitis Cure, Sydney, NSW 2009, Australia
| | - Susan Connor
- Department of Gastroenterology, Liverpool Hospital and South West Sydney Clinical Campuses, UNSW Medicine & Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Steven Leach
- Discipline of Paediatrics, School of Clinical Medicine, University of New South Wales, Sydney, NSW 2033, Australia
| | - Daniel A. Lemberg
- Discipline of Paediatrics, School of Clinical Medicine, University of New South Wales, Sydney, NSW 2033, Australia
- Department of Gastroenterology, Sydney Children’s Hospital, Sydney, NSW 2031, Australia
| | - Yashar Houshyar
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Thisun Jayawardana
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Sabrina Koentgen
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | | | - Georgina L. Hold
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
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Gu H, Wang Y, Wang Y, Ding L, Huan W, Yang Y, Fang F, Cui W. Global Bibliometric and Visualized Analysis of Research on Lactoferrin from 1978 to 2024. Mol Nutr Food Res 2024; 68:e2400379. [PMID: 39044343 DOI: 10.1002/mnfr.202400379] [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: 05/20/2024] [Revised: 07/02/2024] [Indexed: 07/25/2024]
Abstract
SCOPE Lactoferrin (LF) is an iron-bound protein with a molecular weight of about 80 kDa. LF has many biological functions such as antibacterial, antiviral, immunomodulatory, and anticancer. The purpose of this study is to explore the research trend of LF through bibliometric analysis. METHODS AND RESULTS The search is conducted in the Web of Science Core Collection database, and then the publications information of LF related literature is exported. Based on CiteSpace and VOSviewer software, countries, institutions, authors, journals, keywords, and so on are analyzed. Since 1987, a total of 9382 literature have been included, and the number of papers related to LF has increased year by year. These publications come mainly from 124 countries and 725 institutions. Of the 1256 authors analyzed, Valenti Piera is the one with the most publications. The burst strength of gut microbiota, antioxidant, nanoparticles, and in vitro digestion are 21.3, 15.63, 23.03, and 13.51, respectively. They represent the frontier of research in this field and are developing rapidly. CONCLUSION This study shows that LF has important research value. The study of LF nanoparticles and the effects of LF on the gut microbiota are an emerging field that helps to explore new research directions.
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Affiliation(s)
- Hong Gu
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| | - Yiming Wang
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| | - Yating Wang
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| | - Liyi Ding
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| | - Wenru Huan
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| | - Yuting Yang
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| | - Fang Fang
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| | - Weiwei Cui
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
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Oka P, Vibhishanan S, Chetcuti Zammit S, Sidhu R. The utility of capsule endoscopy in the phenotype of Crohn's disease. Data from England 2016-2021. Arab J Gastroenterol 2024; 25:288-292. [PMID: 39048386 DOI: 10.1016/j.ajg.2024.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 05/09/2024] [Accepted: 06/01/2024] [Indexed: 07/27/2024]
Abstract
BACKGROUND AND STUDY AIMS Isolated small bowel Crohn's disease (SBCD) is reported to have a worse prognosis compared to other CD phenotypes. The aim of this study was to understand the correlation between Isolated SBCD and ileocolonic disease with blood and faecal biomarkers and also to identify differences in outcome and management between the two phenotypes. PATIENTS AND METHODS Patients with ileocolonic or isolated small bowel Crohn's Disease (SBCD) were identified from an existing capsule endoscopy (CE) database. Harvey Bradshaw Index (HBI), biomarkers: c-reactive protein (CRP) and faecal calprotectin (FC), Lewis score and findings on CE and subsequent follow up data were collected. SPSS was used to analyse the data. RESULTS In total 248 patients were included in the study. Patients were split into two groups- Isolated SBCD with 178 patient (median age 44 years (IQR 31-56); 41.5 % male) and Ileocolonic Crohn's with 70 patients (median age 31 years (IQR 22.7-49); 31.5 % male). A new diagnosis of SBCD was made in 38.7 % (n = 96), whilst 60.0 % (n = 144) had established CD. Patients with ileocolonic disease had a higher HBI in comparison to isolated SBCD [HBI = 7 (IQR 5-10) vs HBI = 6(IQR 4-9); P = 0.04 ]. There was no significant difference in the FC levels between isolated SBCD and ileocolonic disease [136ug/g (IQR 53.8-363.3) vs 171ug/g (IQR 68.5-485.5); p = 0.98]. In isolated SBCD group, 30.3 % (n = 54) CE showed proximal disease, 96 % (n = 171) showed distal disease and 26.4 % (n = 47) showed extensive disease. SBCE was superior to MRI at diagnosing proximal SBCD (P < 0.01). On multivariate logistic regression, we did not identify any predictors of disease severity defined as Lewis score > 790. Following SBCE, 68.5 % (n = 170) of the total patients had a management change. This included commencement or dose escalation of corticosteroids in 123 (49.5 %) patients, azathioprine in 80 (33.3 %) patients, methotrexate in 22 (9.1 %) patients and biological therapy in 110 (44.3 %) patients. HBI predicted a change in management (p < 0.01). CONCLUSION CE is an important modality for the diagnosis of active SBCD. It also helps guide treatment in patients identified with active disease.
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Affiliation(s)
- Priya Oka
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK; Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK.
| | - Sophie Vibhishanan
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK; Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
| | | | - Reena Sidhu
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK; Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
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Cicerone C, D’Amico F, Allocca M, Zilli A, Parigi TL, Danese S, Furfaro F. A Comprehensive Multidisciplinary Approach to Diagnosing Chronic Inflammatory Bowel Diseases: Integration of Clinical, Endoscopic, and Imaging Modalities. Diagnostics (Basel) 2024; 14:1530. [PMID: 39061667 PMCID: PMC11275644 DOI: 10.3390/diagnostics14141530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 07/12/2024] [Accepted: 07/13/2024] [Indexed: 07/28/2024] Open
Abstract
Chronic inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, present diagnostic challenges due to their complex and heterogeneous nature. While histology remains fundamental for accurate diagnosis, a multidisciplinary approach incorporating clinical, endoscopic, and imaging modalities is increasingly recognized as essential for comprehensive evaluation. This article delves into the importance of integrating various diagnostic techniques in the assessment of IBD. Colonoscopy and histology, with its ability to directly visualize the intestinal mucosa, play a central role in the diagnostic process. However, histological analysis alone may not suffice, necessitating the inclusion of advanced imaging techniques, such as magnetic resonance enterography (MRE), computed tomography enterography (CTE), and intestinal ultrasound (IUS). These techniques provide valuable insights into the disease's extent, severity, and complications, and should be used in conjunction with biochemical parameters. These modalities complement traditional endoscopic and histological findings, offering a more holistic understanding of the disease process. A multidisciplinary approach that incorporates clinical, endoscopic, histological, serological, and imaging assessments enables clinicians to achieve a more accurate and timely diagnosis of IBD. Moreover, this integrated approach facilitates personalized treatment strategies tailored to individual patient needs, ultimately improving clinical outcomes and quality of life for those affected by chronic inflammatory bowel diseases.
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Affiliation(s)
- Clelia Cicerone
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Ferdinando D’Amico
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
- Department of Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
- Department of Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
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Mestrovic A, Perkovic N, Bozic D, Kumric M, Vilovic M, Bozic J. Precision Medicine in Inflammatory Bowel Disease: A Spotlight on Emerging Molecular Biomarkers. Biomedicines 2024; 12:1520. [PMID: 39062093 PMCID: PMC11274502 DOI: 10.3390/biomedicines12071520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/30/2024] [Accepted: 07/06/2024] [Indexed: 07/28/2024] Open
Abstract
Inflammatory bowel diseases (IBD) remain challenging in terms of understanding their causes and in terms of diagnosing, treating, and monitoring patients. Modern diagnosis combines biomarkers, imaging, and endoscopic methods. Common biomarkers like CRP and fecal calprotectin, while invaluable tools, have limitations and are not entirely specific to IBD. The limitations of existing markers and the invasiveness of endoscopic procedures highlight the need to discover and implement new markers. With an ideal biomarker, we could predict the risk of disease development, as well as the possibility of response to a particular therapy, which would be significant in elucidating the pathogenesis of the disease. Recent research in the fields of machine learning, proteomics, epigenetics, and gut microbiota provides further insight into the pathogenesis of the disease and is also revealing new biomarkers. New markers, such as BAFF, PGE-MUM, oncostatin M, microRNA panels, αvβ6 antibody, and S100A12 from stool, are increasingly being identified, with αvβ6 antibody and oncostatin M being potentially close to being presented into clinical practice. However, the specificity of certain markers still remains problematic. Furthermore, the use of expensive and less accessible technology for detecting new markers, such as microRNAs, represents a limitation for widespread use in clinical practice. Nevertheless, the need for non-invasive, comprehensive markers is becoming increasingly important regarding the complexity of treatment and overall management of IBD.
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Affiliation(s)
- Antonio Mestrovic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Nikola Perkovic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Dorotea Bozic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Marko Kumric
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Marino Vilovic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
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Rošić Despalatović B, Babić M, Bratanić A, Tonkić A, Ardalić Ž, Vilović K. The Impact of Phenotype of Inflammatory Bowel Diseases, Inflammation Activity and Therapy on Mucosal Mature Cd83 + Dendritic Cell. J Clin Med 2024; 13:2070. [PMID: 38610835 PMCID: PMC11012704 DOI: 10.3390/jcm13072070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 03/08/2024] [Accepted: 04/02/2024] [Indexed: 04/14/2024] Open
Abstract
Background: Crohn's disease (CD) and ulcerative colitis (UC) are well-defined phenotypes of chronic inflammatory bowel diseases (IBDs). A mechanism of inflammation in these diseases is partially controlled by the intestinal dendritic cell (DC). In this study, we observed a mature CD83+ DC in colonic bioptic samples, and its correlation with disease phenotype and activity. Methods: The study included 219 subjects: 100 with UC, 44 with CD and 75 healthy subjects. Colonic biopsy specimens were incubated with the primary antibody Anti-CD83. Intraepithelial CD83+ DCs were counted per 100 enterocytes. The presence of CD83+ DC was analysed according to the type of IBD, histopathologic inflammation activity and treatment outcome. Results: The presence of mature CD83+ DCs (0, ≥1) differed according to disease types of IBD (p = 0.001), histologic inflammation activity (p = 0.049) and applied therapy (p = 0.001). The odds for CD83+ DC presence were 5.2 times higher in the CD group than in the control/UC group. The odds for CD83+ DC presence were 2.6 times higher in subjects without inflammation or chronic inflammation than with acute inflammation. They were also 3.7 times higher in subjects without therapy. The cut-off value 0.5 CD83+ DC (Rock analysis area = 0.699; SE 0.046; p < 0.001; 95% CI: 0.609-0.788) had been assessed as a differentiation marker between UC and CD. Conclusion: Presence of CD83+ DC could be used as a possible parameter in distinction between UC and CD, as well as a predictor of inflammation activity and treatment outcome.
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Affiliation(s)
| | - Marija Babić
- Medical School, University of Split, 21000 Split, Croatia;
| | - Andre Bratanić
- Department of Gastroenterology and Hepatology, University Hospital Split, 21000 Split, Croatia; (A.T.); (Ž.A.)
| | - Ante Tonkić
- Department of Gastroenterology and Hepatology, University Hospital Split, 21000 Split, Croatia; (A.T.); (Ž.A.)
| | - Žarko Ardalić
- Department of Gastroenterology and Hepatology, University Hospital Split, 21000 Split, Croatia; (A.T.); (Ž.A.)
| | - Katarina Vilović
- Department of Pathology, University Hospital Split, 21000 Split, Croatia;
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Cosier D, Lambert K, Batterham M, Sanderson-Smith M, Mansfield KJ, Charlton K. The INHABIT (synergIstic effect of aNtHocyAnin and proBIoTics in) Inflammatory Bowel Disease trial: a study protocol for a double-blind, randomised, controlled, multi-arm trial. J Nutr Sci 2024; 13:e1. [PMID: 38282655 PMCID: PMC10808876 DOI: 10.1017/jns.2023.113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Accepted: 12/01/2023] [Indexed: 01/30/2024] Open
Abstract
Ulcerative Colitis (UC), a type of Inflammatory Bowel Disease (IBD), is a chronic, relapsing gastrointestinal condition with increasing global prevalence. The gut microbiome profile of people living with UC differs from healthy controls and this may play a role in the pathogenesis and clinical management of UC. Probiotics have been shown to induce remission in UC; however, their impact on the gut microbiome and inflammation is less clear. Anthocyanins, a flavonoid subclass, have shown anti-inflammatory and microbiota-modulating properties; however, this evidence is largely preclinical. To explore the combined effect and clinical significance of anthocyanins and a multi-strain probiotic, a 3-month randomised controlled trial will be conducted in 100 adults with UC. Participants will be randomly assigned to one of four groups: anthocyanins (blackcurrant powder) + placebo probiotic, probiotic + placebo fruit powder, anthocyanin + probiotic, or double placebo. The primary outcome is a clinically significant change in the health-related quality-of-life measured with the Inflammatory Bowel Disease Questionnaire-32. Secondary outcomes include shotgun metagenomic sequencing of the faecal microbiota, faecal calprotectin, symptom severity, and mood and cognitive tests. This research will identify the role of adjuvant anti-inflammatory dietary treatments in adults with UC and elucidate the relationship between the gut microbiome and inflammatory biomarkers in this disease, to help identify targeted individualised microbial therapies. ANZCTR registration ACTRN12623000630617.
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Affiliation(s)
- Denelle Cosier
- School of Medicine, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW, Australia
| | - Kelly Lambert
- School of Medicine, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW, Australia
| | - Marijka Batterham
- Statistical Consulting Centre, National Institute for Applied Statistical Research Australia, University of Wollongong, Wollongong, NSW, Australia
| | - Martina Sanderson-Smith
- School of Chemistry and Molecular Bioscience and Molecular Horizons, University of Wollongong, Wollongong, NSW, Australia
| | - Kylie J Mansfield
- Graduate School of Medicine, University of Wollongong, Wollongong, NSW, Australia
| | - Karen Charlton
- School of Medicine, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW, Australia
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Clinton JW, Cross RK. Personalized Treatment for Crohn's Disease: Current Approaches and Future Directions. Clin Exp Gastroenterol 2023; 16:249-276. [PMID: 38111516 PMCID: PMC10726957 DOI: 10.2147/ceg.s360248] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 12/04/2023] [Indexed: 12/20/2023] Open
Abstract
Crohn's disease is a complex, relapsing and remitting inflammatory disorder of the gastrointestinal tract with a variable disease course. While the treatment options for Crohn's disease have dramatically increased over the past two decades, predicting individual patient response to treatment remains a challenge. As a result, patients often cycle through multiple different therapies before finding an effective treatment which can lead to disease complications, increased costs, and decreased quality of life. Recently, there has been increased emphasis on personalized medicine in Crohn's disease to identify individual patients who require early advanced therapy to prevent complications of their disease. In this review, we summarize our current approach to management of Crohn's disease by identifying risk factors for severe or disabling disease and tailoring individual treatments to patient-specific goals. Lastly, we outline our knowledge gaps in implementing personalized Crohn's disease treatment and describe the future directions in precision medicine.
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Affiliation(s)
- Joseph William Clinton
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Raymond Keith Cross
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
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10
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Kamalova AA, Garina GA, Valeeva IK, Gaifutdinova AR. Fecal calprotectin as a marker of inflammatory bowel diseases. ROSSIYSKIY VESTNIK PERINATOLOGII I PEDIATRII (RUSSIAN BULLETIN OF PERINATOLOGY AND PEDIATRICS) 2023; 68:138-143. [DOI: 10.21508/1027-4065-2023-68-5-138-143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Calprotectin is a calcium- and zinc-binding protein belonging to the S100 protein family. This protein is found mainly in the cytoplasm of neutrophils, and, to a lesser extent, in monocytes and macrophages, which can be found in any human organs, but mainly in blood, cerebrospinal fluid, feces, saliva, and synovial fluid. Calprotectin is an effective tool forthe differential diagnosis of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). There is a connection of fecal calprotectin (FC) with the endoscopic activity of IBD, however, the available literature shows significant differences in the sensitivity and specificity of FC for predicting the endoscopic activity of the disease. In addition, FC can be considered as a predictor of histological mucosal healing and as a marker for assessing the response to treatment, including surgical, but there is still no consensus on the threshold value of a biomarker for these purposes. Conflicting data are presented in reports on FC as a predictor of IBD recurrence. FC seems to be effective for detecting relapse, however, there is no specific threshold value, therefore, the marker cannot completely replace endoscopic examination methods. In addition, there is intraindividual variability in the concentration of FC in patients, depending on age, type of feeding in the first year of life, taking medications, which significantly complicates the interpretation of the results.
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11
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Barnes EL, Darlington K, Herfarth HH. Disease Monitoring of the Ileoanal Pouch: How to Utilize Biomarkers, Imaging, and Pouchoscopy. Curr Gastroenterol Rep 2022; 24:127-136. [PMID: 36255602 DOI: 10.1007/s11894-022-00850-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/12/2022] [Indexed: 12/04/2022]
Abstract
PURPOSE OF REVIEW Restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis has been associated with multiple short- and long-term complications. In this review, we examine the role of biomarkers, imaging, and pouchoscopy in the assessment of patients after ileal pouch-anal anastomosis, with a particular focus on the emergence of novel biomarkers and techniques for evaluating and risk stratifying patients after this procedure in the hopes of improving outcomes in this specific population. RECENT FINDINGS There are indications that that the incidence of pouchitis may be increasing in recent decades. Calprotectin and other non-invasive imaging tests such as ultrasound may offer advantages in distinguishing patients with inflammatory conditions of the pouch from other etiologies. In the search for other biomarkers that may identify patients at risk for inflammatory conditions of the pouch, the stool microbiota and metabolomics may play a key role in identifying those patients at greatest risk for complications. Advances in biomarkers, imaging, and standardized pouchoscopy scoring offer immediate improvements in clinical care and will prompt future research efforts.
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Affiliation(s)
- Edward L Barnes
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Campus Box #7080 130 Mason Farm Road, 27599-7080, Chapel Hill, NC, USA. .,Multidisciplinary Center for Inflammatory Bowel Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. .,Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
| | - Kimberly Darlington
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Campus Box #7080 130 Mason Farm Road, 27599-7080, Chapel Hill, NC, USA
| | - Hans H Herfarth
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Campus Box #7080 130 Mason Farm Road, 27599-7080, Chapel Hill, NC, USA.,Multidisciplinary Center for Inflammatory Bowel Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.,Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Kinugasa T, Mitsuyama K, Murotani K, Mizobe T, Ochi T, Yoshimura T, Kuwaki K, Isobe T, Akagi Y. Non-invasive Monitoring of Pouchitis After Total Proctocolectomy Using Fecal Calprotectin Levels. Kurume Med J 2022; 67:57-63. [PMID: 35944985 DOI: 10.2739/kurumemedj.ms6723005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND Fecal calprotectin (FC) is the most widely used marker for evaluating the disease activity of ulcerative colitis (UC). However, studies on FC in pouchitis after total proctocolectomy are scarce. We aimed to examine the correlations between the FC level and clinical findings and Pouchitis Disease Activity Index (PDAI) in UC patients who underwent total proctocolectomy (TP) with ileal pouch-anal canal anastomosis (IPAA) or ileal pouch-anal canal anastomosis (IACA). METHODS Between April 2008 and March 2018, 15 patients, consisting of 8 males and 7 females, with an average age at operation of 46.5 years, participated in this study. The average observation period was 68.3 months. The subjects underwent FC level measurements and endoscopic examinations. RESULTS The mean FC level was 418.69 μg/g (range: 10-1650 μg/g). Pouchitis was found in one (6.6%) patient, as detected by endoscopy. Among the 15 cases, FC levels were positively correlated with white blood cell count as well as albumin and C-reactive protein levels. There was a significant positive correlation between the PDAI score and FC levels (p<0.05). The median FC level was 111 mg/g in those with pouchitis, which was significantly higher than the 16 mg/g in those without pouchitis (p<0.05). Moreover, a significant positive correlation was found between the endoscopic findings of inflammation and FC levels (p<0.00005). CONCLUSION FC levels were correlated with the PDAI score, blood testing data, and endoscopic findings, suggesting that the FC level could be a useful index of postoperative pouchitis and ileal pouch condition in patients undergoing TP with IPAA as UC treatment.
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Affiliation(s)
- Tetsushi Kinugasa
- Department of Surgery, Department of Medicine, Kurume University School of Medicine
| | - Keiichi Mitsuyama
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Kenta Murotani
- Biostatistics Center, Kurume University Graduate School of Medicine
| | - Tomoaki Mizobe
- Department of Surgery, Department of Medicine, Kurume University School of Medicine
| | - Takafumi Ochi
- Department of Surgery, Department of Medicine, Kurume University School of Medicine
| | - Tetsuhiro Yoshimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Koutarou Kuwaki
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Taro Isobe
- Department of Surgery, Department of Medicine, Kurume University School of Medicine
| | - Yoshito Akagi
- Department of Surgery, Department of Medicine, Kurume University School of Medicine
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Vernia F, Viscido A, Di Ruscio M, Stefanelli G, Valvano M, Latella G. Fecal Lactoferrin and Other Putative Fecal Biomarkers in Crohn's Disease: Do They Still Have a Potential Clinical Role? Digestion 2021; 102:833-844. [PMID: 34518458 DOI: 10.1159/000518419] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 07/11/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several limits, is fecal calprotectin. This review aims to elucidate the role, if any, of all other fecal biomarkers, as alternative tools for assessing clinical and endoscopic disease activity, and predict capsule endoscopy findings, response to therapy, disease relapse, and postoperative recurrence. These fecal biomarkers included lactoferrin, S100A12, high mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, lysozyme, human beta-defensin-2, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, chitinase 3-like-1, M2-pyruvate kinase, myeloperoxidase, and eosinophil proteins. METHODS A systematic electronic search in the medical literature was performed up to April 2020. Seventy eligible studies were identified out of 859 citations. Data were grouped according to the assessment of clinical and endoscopic disease activity, capsule endoscopy findings, response to therapy, prediction of relapse, and postoperative recurrence. RESULTS The overall correlation between lactoferrin and clinical indexes is poor, while performance is good with endoscopic scores. Lactoferrin seems to represent a reasonably good surrogate marker of response to therapy and to be potentially useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence. The evaluation of the performance of all other fecal markers is limited by the lack of adequate data. CONCLUSIONS None of the fecal markers so far represents an acceptable alternative to calprotectin in clinical practice. Fecal lactoferrin is the only possible exception, but a more extensive investigation is still required.
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Affiliation(s)
- Filippo Vernia
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Angelo Viscido
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Mirko Di Ruscio
- IBD Unit of IRCCS Ospedale Sacro Cuore - Don Calabria, Verona, Italy
| | - Gianpiero Stefanelli
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Marco Valvano
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Giovanni Latella
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
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Sorrentino D, Gray JM. Timely Monitoring of Inflammation by Fecal Lactoferrin Rapidly Predicts Therapeutic Response in Inflammatory Bowel Disease. Inflamm Bowel Dis 2021; 27:1237-1247. [PMID: 33501943 PMCID: PMC8314109 DOI: 10.1093/ibd/izaa348] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Fecal lactoferrin (FL) levels may mirror drug-induced changes in inflammation in ulcerative colitis and Crohn disease in a timely way and could be used to assess loss of response (LOR) to biologics. METHODS This study is a retrospective outcome review in 61 patients on adalimumab, infliximab, or vedolizumab managed in our center and followed for 6 to 24 months. Patients were 1) in clinical remission or 2) were experiencing possible LOR. RESULTS For group 1, in 71% of 31 patients, FL slowly increased during the therapeutic interval (R2 = 0.769; P < 0.001), thus reflecting increasing inflammation as drug concentrations decreased. In the remaining patients, FL was undetectable throughout the therapeutic interval because of a stronger suppression of inflammation. For group 2, in 30 patients negative for infections, FL levels measured 1 to 3 days after infusion/injection compared to preadministration values either increased (nonresponders)-in these patients the medication was switched to another class; partially decreased (partial responders)-the therapeutic interval was shortened; or were normal throughout (responders)-causes for symptoms unrelated to disease activity were found for all. After FL-based management, 3-month standardized clinical scores were normalized in both partial responders (0.58 ± 0.21 vs 0.13 ± 0.09; P < 0.001) and nonresponders (0.81 ± 0.17 vs 0.12 ± 0.08; P < 0.001), and FL levels dropped by up to 99%. CONCLUSIONS Levels of FL reflect drug-induced changes in mucosal inflammation in a timely way, thus enabling rapid assessment of therapeutic response in patients with ulcerative colitis and with Crohn disease. In patients with suspected LOR, FL levels before and after infusion/injection accurately separated responders, partial responders, and nonresponders. The strategy proposed here is simple, accurate, and easily applicable to clinical practice.
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Affiliation(s)
- Dario Sorrentino
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA
- Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, Udine, Italy
| | - James M Gray
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA
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Chitinases and Chitinase-Like Proteins as Therapeutic Targets in Inflammatory Diseases, with a Special Focus on Inflammatory Bowel Diseases. Int J Mol Sci 2021; 22:ijms22136966. [PMID: 34203467 PMCID: PMC8268069 DOI: 10.3390/ijms22136966] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/22/2021] [Accepted: 06/24/2021] [Indexed: 11/17/2022] Open
Abstract
Chitinases belong to the evolutionarily conserved glycosyl hydrolase family 18 (GH18). They catalyze degradation of chitin to N-acetylglucosamine by hydrolysis of the β-(1-4)-glycosidic bonds. Although mammals do not synthesize chitin, they possess two enzymatically active chitinases, i.e., chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase), as well as several chitinase-like proteins (YKL-40, YKL-39, oviductin, and stabilin-interacting protein). The latter lack enzymatic activity but still display oligosaccharides-binding ability. The physiologic functions of chitinases are still unclear, but they have been shown to be involved in the pathogenesis of various human fibrotic and inflammatory disorders, particularly those of the lung (idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, sarcoidosis, and asthma) and the gastrointestinal tract (inflammatory bowel diseases (IBDs) and colon cancer). In this review, we summarize the current knowledge about chitinases, particularly in IBDs, and demonstrate that chitinases can serve as prognostic biomarkers of disease progression. Moreover, we suggest that the inhibition of chitinase activity may be considered as a novel therapeutic strategy for the treatment of IBDs.
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Ferreiro Iglesias R, Barreiro-de Acosta M, López J, Bastón Rey I, Domínguez-Muñoz JE. USEFULNESS OF PERIPHERAL BLOOD MONOCYTE COUNT TO PREDICT RELAPSE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A PROSPECTIVE LONGITUDINAL COHORT STUDY. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 114:10-15. [PMID: 33486959 DOI: 10.17235/reed.2021.7683/2020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Monocytes play an important role in the pathogenesis of inflammatory bowel disease but data are scarce as a biomarker of activity, above all, in patients under biologic therapies. The aim was to evaluate the value of monocyte measurements in predicting flares in inflammatory bowel disease patients under maintenance treatment with anti-TNF. A prospective, observational cohort study was designed. Relapse was defined as a Harvey-Bradshaw score >4 in Crohn's disease and a partial Mayo score ≥2 in ulcerative colitis. Monocytes concentration was quantified at 4-month intervals for twelve months. 95 consecutive patients were included. The median age was 42 years, 50.5% female and 75% with Crohn's disease. 65 (68.4%) patients remained in clinical remission. Mean monocyte concentration preceding the relapse was 563 (standard deviation 144) compared to 405 (standard deviation 177) in patients who kept in remission. Final monocytes concentration significantly differentiated between relapse and remission in Crohn's disease (AUC 0.82; 95% CI: 0.71-0.90; P <0.005). In the multivariate analysis, only monocytes and fecal calprotectin related to more relapses. In conclusion, in inflammatory bowel disease patients under anti-TNF therapy, repeated monocytes concentration could help in order to monitoring patients, at least, in Crohn's disease.
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Affiliation(s)
| | | | - Javier López
- Servicio de Aparato Digestivo, Hospital Clinico Universitario de Santiago
| | - Iria Bastón Rey
- Servicio de Digestivo, Hospital Clínico Universitario de Santiago
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Shentova-Eneva R, Velikova T. Laboratory Assessment of Disease Activity in Pediatric Patients with Inflammatory Bowel Disease: What’s New? GASTROENTEROLOGY INSIGHTS 2020; 11:58-71. [DOI: 10.3390/gastroent11020009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Laboratory tests are an integral part of both the diagnostic and follow-up algorithm of patients with inflammatory bowel disease (IBD). Their advantages over other non-invasive methods for assessing disease activity are greater objectivity than clinical activity indices and imaging studies. This review aims to analyze shortly the most common laboratory tests used to assess disease activity in pediatric patients with IBD. In addition to the conventional blood and serum markers that are not specific for gut inflammation, although routinely used, we also reviewed the established fecal markers such as calprotectin, lactoferrin, M2-pyruvate kinase, osteoprotegerin, HMGB1, chitinase 3-like 1, and the promising non-coding microRNA. In conclusion, neither marker is unique to the pediatric IBD. More clinical data are required to assess biomarkers’ full potential for diagnosis, management, and follow-up of pediatric IBD patients.
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Affiliation(s)
- Rayna Shentova-Eneva
- Department of Gastroenterology and Hepatology, Medical Faculty, University Children’s Hospital “Professor Ivan Mitev”, Medical University, 16 Akademik Ivan Evstratiev Geshov Blvd, 1606 Sofia, Bulgaria
| | - Tsvetelina Velikova
- Clinical Immunology, Medical Faculty, University Hospital “Lozenetz,”, Sofia University St. Kliment Ohridski, Kozyak 1 Street, 1407 Sofia, Bulgaria
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18
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Rodrigues BL, Mazzaro MC, Nagasako CK, Ayrizono MDLS, Fagundes JJ, Leal RF. Assessment of disease activity in inflammatory bowel diseases: Non-invasive biomarkers and endoscopic scores. World J Gastrointest Endosc 2020; 12:504-520. [PMID: 33362904 PMCID: PMC7739141 DOI: 10.4253/wjge.v12.i12.504] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 10/06/2020] [Accepted: 11/05/2020] [Indexed: 02/05/2023] Open
Abstract
Inflammatory bowel diseases (IBD) comprise two major forms: Crohn's disease and ulcerative colitis. The diagnosis of IBD is based on clinical symptoms combined with results found in endoscopic and radiological examinations. In addition, the discovery of biomarkers has significantly improved the diagnosis and management of IBD. Several potential genetic, serological, fecal, microbial, histological and immunological biomarkers have been proposed for IBD, and they have been evaluated for clinical routine and clinical trials. Ileocolonoscopy, especially with biopsy collection, has been considered the standard method to diagnose IBD and to assess clinical activity of the disease, but it is limited to the colon and terminal ileum and is considered invasive. For this reason, non-invasive biomarkers are necessary for this type of chronic inflammatory disease, which affects mostly young individuals, as they are expected to have a long follow-up.
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Affiliation(s)
- Bruno Lima Rodrigues
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Márcia Carolina Mazzaro
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Cristiane Kibune Nagasako
- Department of Gastroenterology, Gastrocenter, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Maria de Lourdes Setsuko Ayrizono
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - João José Fagundes
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Raquel Franco Leal
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
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Khaki-Khatibi F, Qujeq D, Kashifard M, Moein S, Maniati M, Vaghari-Tabari M. Calprotectin in inflammatory bowel disease. Clin Chim Acta 2020; 510:556-565. [PMID: 32818491 PMCID: PMC7431395 DOI: 10.1016/j.cca.2020.08.025] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/11/2020] [Accepted: 08/13/2020] [Indexed: 02/07/2023]
Abstract
The term IBD is usually used for referring to a group of inflammatory gastro-intestinal diseases (mainly Crohn's disease and ulcerative colitis). Accordingly, IBD arises as a result of inappropriate immune response to intestinal commensal organisms among genetically susceptible individuals. Performing colonoscopy and histopathologic evaluation on an inflamed bowel biopsy specimen are currently considered as gold standards for diagnosis and management of IBD. Correspondingly, these techniques are known to be invasive and costly. In recent decades, fecal calprotectin, as a biomarker, has received much attention for the diagnosis and non-invasive management of IBD. Up to now, many studies have investigated the efficacy of fecal calprotectin in the areas of IBD differentiation from IBS, prediction of endoscopic and histologic activities of IBD and prediction of disease recurrence. Although some of these studies have reported promising results, some others have shown significant limitations. Therefore, in this paper, we reviewed the most interesting ones of these studies after a brief discussion of the laboratory measurement of fecal calprotectin. Moreover, we attempted to provide an answer for the question of whether fecal-calprotectin could be considered as a potential surrogate marker for colonoscopy.
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Affiliation(s)
- Fatemeh Khaki-Khatibi
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Durdi Qujeq
- Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran,Department of Clinical Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Mehrdad Kashifard
- Department of Internal Medicine, Gastroenterology Division, Ayatollah Rouhani Hospital, Babol University of Medical Sciences, Babol, Iran
| | - Soheila Moein
- Department of Biochemistry, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Mahmood Maniati
- English Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mostafa Vaghari-Tabari
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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20
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Dai C, Jiang M, Sun MJ, Cao Q. Fecal Lactoferrin for Assessment of Inflammatory Bowel Disease Activity: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2020; 54:545-553. [PMID: 30994521 DOI: 10.1097/mcg.0000000000001212] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Persistent disease activity is associated with a poor prognosis in inflammatory bowel disease (IBD) patients. Therefore, monitoring of IBD activity can avoid the poor prognosis. Serum biomarkers reflect a summation of systemic host responses rather than being specific for intestinal inflammation. And endoscopic monitoring is invasive, costly, and time consuming. The objective of our study was to perform a meta-analysis evaluating the diagnostic accuracy of fecal lactoferrin (FL) in assessing IBD activity. METHODS We systematically searched the databases from inception to May 2018 that evaluated IBD activity. 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 Ten studies comprising 773 IBD patients were included in the meta-analysis. The pooled sensitivity and specificity values for assessing ulcerative colitis (UC) activity were 0.81 [95% confidence interval (CI), 0.64-0.92] and 0.82 (95% CI, 0.61-0.93), respectively. And the pooled sensitivity and specificity values for assessing Crohn's disease (CD) activity were 0.82 (95% CI, 0.73-0.88) and 0.71 (95% CI, 0.63-0.78), respectively. The diagnostic performance of the FL assay in the UC patients appeared to be superior to that in the CD patients. CONCLUSION Our meta-analysis has found that FL is an inexpensive, simple, stable, and useful screening marker with high sensitivity and modest specificity for assessing IBD activity, appearing to have greater ability to evaluate UC rather than CD.
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Affiliation(s)
- Cong Dai
- Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China
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21
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Rubio MG, Amo-Mensah K, Gray JM, Nguyen VQ, Nakat S, Grider D, Love K, Boone JH, Sorrentino D. Fecal lactoferrin accurately reflects mucosal inflammation in inflammatory bowel disease. World J Gastrointest Pathophysiol 2019; 10:54-63. [PMID: 31911845 PMCID: PMC6940564 DOI: 10.4291/wjgp.v10.i5.54] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 12/12/2019] [Accepted: 12/23/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Studies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin (FC) and fecal lactoferrin (FL) in monitoring inflammatory bowel diseases (IBD) - Crohn’s disease (CD) and ulcerative colitis (UC). However, their correlation to endoscopic scores, disease severity and affected intestinal surface has not been extensively investigated.
AIM To correlate FL, and for comparison white blood cell (WBC) and C-reactive protein (CRP), with endoscopic scores, disease extent and location in CD and UC.
METHODS Retrospective analysis in 188 patients who had FL, CRP and WBC determined within 30 d of endoscopy. Disease location, disease extent (number of intestinal segments involved), disease severity (determined by endoscopic scores), timing of FL testing in relation to colonoscopy, as well as the use of effective fast acting medications (steroids and biologics) between colonoscopy and FL measurement, were recorded.
RESULTS In 131 CD and 57 UC patients, both CRP and FL - but not WBC - distinguished disease severity (inactive, mild, moderate, severe). In patients receiving fast-acting (steroids or biologics) treatment in between FL and colonoscopy, FL showed a higher correlation to endoscopic scores when tested before vs after the procedure (r = 0.596, P < 0.001, vs r = 0.285, P = 0.15 for the Simple Endoscopic Score for CD; and r = 0.402, P = 0.01 vs r = 0.054 P = 0.84 for Disease Activity Index). Finally, FL was significantly correlated with the diseased mucosal surface (colon-ileocolon > small bowel) and the number of inflamed colon segments.
CONCLUSION FL and CRP separated disease severity categories with FL showing lower discriminating P-values. FL showed a close correlation with the involved mucosal surface and with disease extent and was more closely correlated to endoscopy when determined before the procedure – this indicating that inflammatory activity changes associated with therapy might be rapidly reflected by FL levels. FL can accurately and timely characterize intestinal inflammation in IBD.
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Affiliation(s)
- Marrieth G Rubio
- IBD Center - Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, United States
| | - Kofi Amo-Mensah
- IBD Center - Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, United States
| | - James M Gray
- IBD Center - Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, United States
| | - Vu Q Nguyen
- IBD Center - Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, United States
| | - Sam Nakat
- Department of Radiology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, United States
| | - Douglas Grider
- Department of Basic Science Education; Virginia Tech Carilion School of Medicine and Dominion Pathology Associates, Roanoke, VA 24016, United States
| | - Kim Love
- K. R. Love Quantitative Consulting and Collaboration, Athens, GA 30605, United States
| | - James H Boone
- Research and Development, TECHLAB Inc, Blacksburg, VA 24060, United States
| | - Dario Sorrentino
- IBD Center - Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, United States
- Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, Udine 33100, Italy
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22
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Shentova R, Baycheva M, Hadjiiski P, Kofinova D, Yaneva P. Role of faecal calprotectin as a predictor of endoscopic activity in paediatric patients with ulcerative colitis. GASTROENTEROLOGIA Y HEPATOLOGIA 2019; 43:57-61. [PMID: 31733888 DOI: 10.1016/j.gastrohep.2019.08.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 05/31/2019] [Accepted: 08/21/2019] [Indexed: 12/01/2022]
Abstract
INTRODUCTION Colonoscopy is currently considered to be the gold standard for evaluation of colonic mucosa inflammation in patients with ulcerative colitis (UC), but the procedure is invasive and cannot be repeated frequently, especially in the paediatric population. The aim of this study was to assess the role of faecal calprotectin (FC) as a predictor of endoscopic disease activity in paediatric patients with UC in clinical remission. MATERIAL AND METHODS Single-centre prospective study. Clinical remission was defined as Paediatric Ulcerative Colitis Activity Index <10. Endoscopic findings were assessed according to the Mayo Endoscopic Subscore (MES). MES≤1 was defined as endoscopic remission. All participants provided fresh faecal samples for measurement of FC. RESULTS A total of 34 visits of 24 children with UC were included in the study. There was a strong positive correlation between FC levels and endoscopic disease activity (n=34, r=0.83, p<0.001). The median FC levels in the subgroup with endoscopic activity (MES 2-3) were significantly higher than the median FC levels in the subgroup without endoscopic activity (MES≤1) (1000μg/g, IQR 575-1800μg/g vs. 100μg/g, IQR 80-223μg/g, p<0.001). At a cut-off of 298.5μg/g, FC had 92.3% sensitivity, 95.2% specificity and an AUROC 0.974 (SE 0.023, 95% CI 0.93-1, p<0.001) to predict endoscopic activity. DISCUSSION FC is an accurate surrogate marker of endoscopic activity in children with clinically quiescent UC.
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Affiliation(s)
- Rayna Shentova
- Departamento de Gastroenterología y Hepatología, Hospital Universitario Pediátrico "Prof. Ivan Mitev", Universidad de Medicina de Sofía, Bulgaria.
| | - Mila Baycheva
- Departamento de Gastroenterología y Hepatología, Hospital Universitario Pediátrico "Prof. Ivan Mitev", Universidad de Medicina de Sofía, Bulgaria
| | - Petio Hadjiiski
- Departamento de Gastroenterología y Hepatología, Hospital Universitario Pediátrico "Prof. Ivan Mitev", Universidad de Medicina de Sofía, Bulgaria
| | - Denitza Kofinova
- Departamento de Gastroenterología y Hepatología, Hospital Universitario Pediátrico "Prof. Ivan Mitev", Universidad de Medicina de Sofía, Bulgaria
| | - Penka Yaneva
- Departamento de Gastroenterología y Hepatología, Hospital Universitario Pediátrico "Prof. Ivan Mitev", Universidad de Medicina de Sofía, Bulgaria
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23
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Bannaga AS, Farrugia A, Arasaradnam RP. Diagnosing Inflammatory bowel disease using noninvasive applications of volatile organic compounds: a systematic review. Expert Rev Gastroenterol Hepatol 2019; 13:1113-1122. [PMID: 31657950 DOI: 10.1080/17474124.2019.1685873] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Introduction: Inflammatory bowel disease (IBD) is a common disease with significant morbidity. Noninvasive diagnostic techniques are lacking in IBD. Currently, fecal calprotectin is a sensitive marker of gut inflammation however is not specific to Crohn's disease (CD) or ulcerative colitis (UC) alone. Volatile organic compounds (VOCs) were shown to have potential in IBD diagnosis.Areas covered: This systematic review aimed to examine the next-generation diagnosis of IBD in adults and children using VOCs. An in-depth literature-based search of current clinical studies of VOCs in the diagnosis of IBD was undertaken. Accuracy of IBD detection varied according to the technologies applied. Breath VOCs studies were pooled giving an overall sensitivity of 85% (95%CI: 79-89%) and specificity of 79% (95%CI 73-84%) whilst pooled fecal VOCs studies revealed a sensitivity of 87% (95%CI 77-93%) and specificity of 91% (95%CI 82-96%). Studies were limited by the variance of techniques applied in VOCs detection and the absence of well-designed longitudinal studies.Expert opinion: VOCs can be consistently and effectively detected in urine, breath, and stool in IBD patients. The sensitivity of breath VOCs in detecting IBD was comparable to feces. However, optimal VOCs detection methodology and biological sampling still need to be standardized..
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Affiliation(s)
- Ayman S Bannaga
- University Hospital Coventry and Warwickshire NHS Trust, Coventry, UK.,Warwick Medical School, University of Warwick, Coventry, UK
| | - Alexia Farrugia
- University Hospital Coventry and Warwickshire NHS Trust, Coventry, UK.,Warwick Medical School, University of Warwick, Coventry, UK
| | - Ramesh P Arasaradnam
- University Hospital Coventry and Warwickshire NHS Trust, Coventry, UK.,Warwick Medical School, University of Warwick, Coventry, UK.,Faculty of Health Science, University of Coventry, Coventry, UK.,Division of Health Sciences, University of Leicester, Leicester, UK
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24
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Cerrillo E, Moret I, Iborra M, Pamies J, Hervás D, Tortosa L, Sáez-González E, Nos P, Beltrán B. A Nomogram Combining Fecal Calprotectin Levels and Plasma Cytokine Profiles for Individual Prediction of Postoperative Crohn's Disease Recurrence. Inflamm Bowel Dis 2019; 25:1681-1691. [PMID: 30925193 DOI: 10.1093/ibd/izz053] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aims of this study were to characterize the immune response profile in patients with Crohn's disease (CD) and early postoperative recurrence (POR), to identify predictive biomarkers, and to develop a noninvasive predictive tool for individual estimation of POR risk. METHODS Sixty-one patients who had undergone ileocolonic resection for CD were prospectively included and followed up for 24 months. Fecal calprotectin (FC), analytical parameters, and plasma cytokines were obtained before surgery and at various time points during postoperative follow-up. Morphological recurrence was assessed by ileocolonoscopy or magnetic resonance enterography within 6-12 months after surgery. Clinical activity was scored using the Harvey-Bradshaw Index. RESULTS Twenty-seven patients (44.3%) had morphological recurrence during follow-up. Fecal calprotectin values were significantly associated with POR risk over time. The receiver operating characteristic curve for FC provided an area under the curve (AUC) of 0.88 (95% confidence interval, 0.75-0.96), and morphological recurrence was best predicted by FC ≥160 μg/g at 6 months after surgery (85% sensitivity, 70% specificity, 26% predictive positive value, 98% negative predictive value [NPV]). The plasma cytokine profile showed higher presurgery interleukin (IL)-13 plasma levels and higher IL-6 and interferon (IFN)-γ levels at 6 months after surgery in patients with POR compared with patients without recurrence. The combination of FC, IL-6, and IFN-γ values at 6 months gave an AUC of 0.90 for predicting an early recurrence. CONCLUSIONS FC values <160 μg/g at 6 months have a high NPV to rule out early lesions. Combined values of FC, IL-6, and IFN-γ levels at 6 months postsurgery constitute a prognostic index with a high predictive capacity to assess the risk of early POR.
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Affiliation(s)
- Elena Cerrillo
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - Inés Moret
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - Marisa Iborra
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - José Pamies
- Radiology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - David Hervás
- Biostatistics Unit, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
| | - Luis Tortosa
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
| | - Esteban Sáez-González
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
| | - Pilar Nos
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - Belén Beltrán
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
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25
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Engström J, Lönnkvist M, Befrits R, Ljung T, Diaz-Tartera H, Holst M, Hellström PM. Comparison of fecal calprotectin and serum C-reactive protein in early prediction of outcome to infliximab induction therapy. Scand J Gastroenterol 2019; 54:1081-1088. [PMID: 31499013 DOI: 10.1080/00365521.2019.1660402] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background: Fecal calprotectin (FC) and serum C-reactive protein (CRP) are biomarkers of disease activity in Crohn's disease (CD) and ulcerative colitis (UC). We assessed FC, CRP, Harvey-Bradshaw index (HBi), partial Mayo Clinic Scoring (pMCS) and a cytokine panel during infliximab induction to predict therapy outcome. Methods: FC, CRP and clinical indices were evaluated in 123 (76 CD, 47 UC) patients before infliximab induction and after 12 weeks. Responders were monitored 48 weeks for an 'incident' (dosage increase, shortened dosage interval, surgery). Cutoff values for FC and CRP were obtained using receiver-operating characteristics (ROC). Disease progression was analyzed with Kaplan-Meier survivals, log-rank test and logistic regression for combined biomarkers. Cytokines were analyzed with Luminex multiplexing system. Results: Following infliximab, FC and CRP declined (p < .0001) along with HBi for CD and pMCS for UC. Simultaneously, IL-6 and TNF-α decreased, while IL-10 increased. Optimal FC ROC cutoff was 221 µg/g (sensitivity 66%, specificity 67%, AUC 0.71) and CRP ROC cutoff 2.1 mg/L (sensitivity 54%, specificity 60%, AUC 0.58). In CD, FC > 221 µg/g (p < .0001), but not CRP > 2.1 mg/L predicted an 'incident'. However, combined FC and CRP also predicted an 'incident' (p < .042). In UC, both FC > 221 µg/g (p < .0005) and CRP > 2.1 mg/L (p = .0334) predicted 'incident', as did combined biomarkers (p < .005). Conclusions: Clinical disease activity is reduced by treatment with infliximab. In CD, persistently high FC, but not CRP, predict a treatment 'incident', whereas in UC both high FC and high CRP predict 'incident'. Combined FC and CRP values also predict an 'incident'.
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Affiliation(s)
- Johanna Engström
- Department of Medical Sciences, Gastroenterology and Hepatology, Uppsala University , Uppsala , Sweden
| | - Maria Lönnkvist
- Department of Medical Sciences, Gastroenterology and Hepatology, Uppsala University , Uppsala , Sweden
| | - Ragnar Befrits
- Department of Medicine, Gastroenterology and Hepatology, Karolinska University Hospital Solna, Karolinska Institutet , Stockholm , Sweden
| | - Tryggve Ljung
- Department of Medical Sciences, Gastroenterology and Hepatology, Uppsala University , Uppsala , Sweden
| | - Hetzel Diaz-Tartera
- Department of Medical Sciences, Gastroenterology and Hepatology, Uppsala University , Uppsala , Sweden
| | - Mikael Holst
- Department of Women's and Children's Health, Karolinska University Hospital Solna, Karolinska Institutet , Stockholm , Sweden
| | - Per M Hellström
- Department of Medical Sciences, Gastroenterology and Hepatology, Uppsala University , Uppsala , Sweden
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26
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Azramezani Kopi T, Amini Kadijani A, Parsian H, Shahrokh S, Asadzadeh Aghdaei H, Mirzaei A, Balaii H, Zali MR. The value of mRNA expression of S100A8 and S100A9 as blood-based biomarkers of inflammatory bowel disease. Arab J Gastroenterol 2019; 20:135-140. [PMID: 31563476 DOI: 10.1016/j.ajg.2019.07.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 06/14/2019] [Accepted: 07/17/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND STUDY AIMS Non-invasive biomarkers of inflammatory bowel diseases (IBD) are of critical importance. Here, we evaluated the S100A8 and S100A9 mRNA expression, as the heterodimers of calprotectin, in the blood leucocytes of IBD patients to find how their expression associates with the disease characteristics. PATIENTS AND METHODS In this cross-sectional study, 59 IBD patients and 30 healthy subjects were included. The flare and remission phases of disease were identified in 46 and 13 patients, respectively. Blood leucocytes were isolated, and the S100A8 and S100A9 mRNA expression were evaluated in the isolated leucocytes using relative quantification real-time PCR. RESULTS The mean S100A8 and S100A9 mRNA expression were significantly higher in IBD patients than in the controls (p = 0.03 and p = 0.02, respectively). The mean S100A8 and S100A9 mRNA expression were significantly higher in the flare phase of the disease compared with the remission phase (p = 0.01 and p = 0.007, respectively). S100A8 distinguished IBD patients from controls with the sensitivity and specificity of 73% and 64%, and flare phase of disease from remission with the sensitivity and specificity of 67% and 62%. On the other hand, S100A9 distinguished IBD patients from controls with the sensitivity and specificity of 81% and 70%, and flare phase of disease from remission with the sensitivity and specificity of 68% and 64%. CONCLUSION The S100A8 and S100A9 mRNA are differentially expressed in blood leucocytes of IBD patients compared to healthy controls as well as active versus quiescent disease. Thus, they can be potentially used as a blood-based biomarker in the monitoring of IBD.
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Affiliation(s)
- Tayebeh Azramezani Kopi
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran; Cellular and Molecular Biology Research Centre, Babol University of Medical Sciences, Babol, Iran
| | - Azade Amini Kadijani
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hadi Parsian
- Social Determinant of Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Shabnam Shahrokh
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Alireza Mirzaei
- Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Hedieh Balaii
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Celi P, Verlhac V, Pérez Calvo E, Schmeisser J, Kluenter AM. Biomarkers of gastrointestinal functionality in animal nutrition and health. Anim Feed Sci Technol 2019. [DOI: 10.1016/j.anifeedsci.2018.07.012] [Citation(s) in RCA: 94] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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28
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Damião AOMC, Azevedo MFCD, Carlos ADS, Wada MY, Silva TVM, Feitosa FDC. Conventional therapy for moderate to severe inflammatory bowel disease: A systematic literature review. World J Gastroenterol 2019; 25:1142-1157. [PMID: 30863001 PMCID: PMC6406187 DOI: 10.3748/wjg.v25.i9.1142] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 01/28/2019] [Accepted: 02/16/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Despite the advent of biological drugs, conventional therapy continues to be used in moderate to severe inflammatory bowel disease (MS-IBD). This study hypothesized that as a standard of treatment and the primary alternative to biologics, conventional therapy should present robust effectiveness results in IBD outcomes.
AIM To investigate the effectiveness of conventional therapy for MS-IBD.
METHODS A systematic review with no time limit was conducted in July 2017 through the Cochrane Collaboration, MEDLINE, and LILACS databases. The inclusion criteria encompassed meta-analyses, systematic reviews, randomized clinical trials, observational and case-control studies concerning conventional therapy in adult patients with MS-IBD, including Crohn’s disease (CD) and ulcerative colitis (UC). Corticosteroids (prednisone, hydrocortisone, budesonide, prednisolone, dexamethasone), 5-aminosalicylic acid (5-ASA) derivatives (mesalazine and sulfasalazine) and immunosuppressants [azathioprine (AZA), methotrexate (MTX), mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine (6-MP)] were considered conventional therapy. The exclusion criteria were sample size below 50; narrative reviews; specific subpopulations (e.g., pregnant women, comorbidities); studies on postoperative IBD; and languages other than English, Spanish, French or Portuguese. The primary outcome measures were clinical remission (induction or maintenance), clinical response and mucosal healing. As secondary outcomes, fecal calprotectin, hospitalization, death, and surgeries were analyzed. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation criteria.
RESULTS The search strategy identified 1995 citations, of which 27 were considered eligible (7 meta-analyses, 20 individual studies). For induction of clinical remission, four meta-analyses were selected (AZA and 6-MP showed no advantage over placebo, MTX or 5-ASA in CD; MTX showed no statistically significant difference versus placebo, 6-MP, or 5-ASA in UC; tacrolimus was superior to placebo for UC in two meta-analyses). Only one meta-analysis evaluated clinical remission maintenance, showing no statistically significant difference between MTX and placebo, 5-ASA, or 6-MP in UC. AZA and 6-MP had no advantage over placebo in induction of clinical response in CD. Three meta-analyses showed the superiority of tacrolimus vs placebo for induction of clinical response in UC. The clinical response rates for cyclosporine were 41.7% in randomized controlled trials (RCTs) and 55.4% in non-RCTs for UC. For induction of mucosal healing, one meta-analysis showed a favorable rate with tacrolimus versus placebo for UC. For secondary outcomes, no meta-analyses specifically evaluated fecal calprotectin, hospitalization or death. Two meta-analyses were retrieved evaluating colectomy rates for tacrolimus and cyclosporine in UC. Most of the twenty individual studies retrieved contained a low or very low quality of evidence.
CONCLUSION High-quality evidence assessing conventional therapy in MS-IBD treatment is scarce, especially for remission maintenance, mucosal healing and fecal calprotectin.
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Affiliation(s)
| | | | - Alexandre de Sousa Carlos
- Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo 05403-000, Brazil
| | - Marcela Yumi Wada
- Department of Medical Affairs, Takeda Pharmaceuticals, São Paulo 04709-011, Brazil
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29
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Daniluk U, Daniluk J, Krasnodebska M, Lotowska JM, Sobaniec-Lotowska ME, Lebensztejn DM. The combination of fecal calprotectin with ESR, CRP and albumin discriminates more accurately children with Crohn's disease. Adv Med Sci 2019; 64:9-14. [PMID: 30237086 DOI: 10.1016/j.advms.2018.08.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Revised: 06/11/2018] [Accepted: 08/03/2018] [Indexed: 12/19/2022]
Abstract
PURPOSE Increased fecal calprotectin is a sensitive marker of various types of intestinal inflammation. We investigated correlations between high fecal calprotectin concentration and serum inflammatory markers in children with different intestinal diseases with diarrhea with/without blood and/or abdominal pain, to test whether the combination of these markers can differentiate potential patients with inflammatory bowel disease. MATERIALS/METHODS The study included 128 children with high fecal calprotectin concentration (>150ug/g) and symptoms suggesting bowel disorders, hospitalized in the years 2013- 2015. Twenty-six (20%) patients were diagnosed with Crohn's disease, 55 (43%) with ulcerative colitis, 32 (25%) with intestinal infection and 15 (12%) with food protein induced proctocolitis. RESULTS Significantly increased inflammatory markers were detected in children with inflammatory bowel disease, with a correlation between calprotectin and erythrocyte sedimentation rate - ESR (R = 0.53), mean corpuscular volume - MCV (R=-0.64), red blood cell distribution width (R = 0.56), albumin (R = -0.52), hemoglobin (R = -0.53) only in Crohn's disease patients. To discriminate Crohn's disease patients from patients with intestinal infection and patients with food protein induced proctocolitis, AUC analysis was performed. It revealed that considering ESR, CRP and albumin as additional markers to fecal calprotectin significantly improved diagnostic performance (AUC 0.917, p = 0.038). CONCLUSIONS In children with abdominal pain and/or diarrhea, increased ESR, CRP and decreased albumin combined with a high fecal calprotectin level yields additional diagnostic value in screening potential patients with Crohn's disease. As far as differentiation of ulcerative colitis is concerned, low additional diagnostic value was found when high fecal calprotectin was combined with albumin.
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Affiliation(s)
- Urszula Daniluk
- Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, Bialystok, Poland.
| | - Jaroslaw Daniluk
- Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Milena Krasnodebska
- Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, Bialystok, Poland
| | - Joanna Maria Lotowska
- Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok, Poland
| | | | - Dariusz Marek Lebensztejn
- Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, Bialystok, Poland
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Dai C, Jiang M, Sun MJ. Fecal markers in the management of inflammatory bowel disease. Postgrad Med 2018; 130:597-606. [PMID: 30063872 DOI: 10.1080/00325481.2018.1503919] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 07/20/2018] [Indexed: 12/13/2022]
Abstract
Inflammatory bowel disease (IBD) is characterized by periods of symptomatic remission and relapse. Diagnosis and assessment of IBD are based on clinical evaluation, serum parameters, radiology, and endoscopy. Fecal markers have emerged as new diagnostic tools to detect and monitor intestinal inflammation. Fecal calprotectin (FC) and lactoferrin (FL) were identified decades ago as potentially revolutionary markers for IBD. Following these discoveries numerous additional markers, including S100A12, M2-PK, metalloproteinases, hemoglobin, myeloperoxidase, lysozyme, polymorphonuclear elastase, neopterin, and nitric oxide, have also been suggested as novel markers of IBD. But only FC and FL are used for the management of clinical IBD patients. The objective of this review is to introduce the clinical applications of fecal markers in the diagnosis, monitoring and prediction of outcomes of inflammatory bowel disease.
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Affiliation(s)
- Cong Dai
- a Department of Gastroenterology, First Affiliated Hospital , China Medical University , Shenyang , China
| | - Min Jiang
- a Department of Gastroenterology, First Affiliated Hospital , China Medical University , Shenyang , China
| | - Ming-Jun Sun
- a Department of Gastroenterology, First Affiliated Hospital , China Medical University , Shenyang , China
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Fecal Matrix Metalloprotease-9 and Lipocalin-2 as Biomarkers in Detecting Endoscopic Activity in Patients With Inflammatory Bowel Diseases. J Clin Gastroenterol 2018; 52:e53-e62. [PMID: 28723856 DOI: 10.1097/mcg.0000000000000837] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Fecal biomarkers are emerging tools in the assessment of mucosal healing in inflammatory bowel diseases (IBD). GOALS We aimed to evaluate the accuracy of fecal matrix metalloprotease-9 (MMP-9) and fecal lipocalin-2 (LCN-2) compared with calprotectin in detecting endoscopic activity in IBD STUDY:: Overall, 86 IBD adults underwent colonoscopy consecutively and prospectively, with Crohn's disease Endoscopic Index of Severity (CDEIS) in Crohn's disease (CD) patients or Mayo endoscopic subscore calculation for ulcerative colitis (UC) patients, and stool collection. Fecal calprotectin was measured using quantitative immunochromatographic testing. Fecal MMP-9 and LCN-2 was quantified by enzyme-linked immunosorbent assay. MMP-9 and LCN-2 thresholds were determined using receiver operating curves. RESULTS In 54 CD patients, fecal calprotectin, MMP-9 and LCN-2 correlated with CDEIS and were significantly increased in patients with endoscopic ulcerations. MMP-9 >350 ng/g detected endoscopic ulceration in CD with a sensitivity of 90.0% and a specificity of 63.6%, compared with fecal calprotectin >250 μg/g (sensitivity=90.5% and specificity=59.1%). Fecal LCN-2 demonstrated lower performances than the 2 other biomarkers (sensitivity=85.7% and specificity=45.5%).In 32 UC patients, fecal MMP-9, LCN-2, and calprotectin levels were significantly increased in patients with endoscopic activity. In UC patients, fecal MMP-9 >900 ng/g had the best efficacy to detect endoscopic activity (sensitivity=91.0% and specificity=80.0%, compared with fecal calprotectin >250 μg/g (sensitivity=86.4% and specificity=80.0%) and LCN-2 >6700 ng/g (sensitivity=82.0% and specificity=80.0%). CONCLUSIONS Fecal MMP-9 is a reliable biomarker in detecting endoscopic activity in both UC and CD patients.
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Role of fecal calprotectin as a biomarker of intestinal inflammation in ulcerative colitis: a prospective study. REV ROMANA MED LAB 2018. [DOI: 10.2478/rrlm-2018-0006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Abstract
Background: The clinical utility of non-invasive markers in the diagnosis and monitoring of ulcerative colitis (UC) has been intensively studied. The aim of our study was to evaluate the value of fecal calprotectin (FC) in differentiating between UC and irritable bowel syndrome (IBS), and in estimating inflammatory activity in UC.
Method: A total number of 140 patients were included in the study. All patients underwent ileocolonoscopy with biopsies, quantitative determination of FC, and blood tests (white blood cell count, CRP, ESR). The severity of UC was assessed by using the Ulcerative Colitis Disease Activity Index (UCDAI) and Mayo endoscopic score.
Results: In patients with active UC the mean values of FC were 373.8 +/- 146.3 μg/g, significantly higher than those in the inactive UC (mean values 36.04 +/- 13.25 μg/g), and in IBS (42.9 +/- 16.00 μg/g). In univariate regression analysis, elevated FC levels strongly correlated with pancolitis (p=0.0001), UCDAI and Mayo scores (p=0.0001), and elevated CRP levels. In multivariate regression model, FC was positively associated with severe pancolitis, and elevated CRP. The optimal cutoff value of FC for the prediction of severe pancolitis (Mayo score˃ 3) was 540 μg/g. We obtained 71.4% sensitivity (CI95%: 41.95-91.6) and 96.1% specificity (CI95%: 89.2 -99.2) of FC in assessing the severity of inflammation in UC patients.
Conclusion: FC is a promising marker that can be used in clinical practice to select patients with organic intestinal disorders, compared with those with functional disorders. It also correlates very well with the extent of lesions and the severity of clinical symptoms in UC, with increased sensitivity and specificity.
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Heilmann RM, Berghoff N, Mansell J, Grützner N, Parnell NK, Gurtner C, Suchodolski JS, Steiner JM. Association of fecal calprotectin concentrations with disease severity, response to treatment, and other biomarkers in dogs with chronic inflammatory enteropathies. J Vet Intern Med 2018; 32:679-692. [PMID: 29460444 PMCID: PMC5866976 DOI: 10.1111/jvim.15065] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 01/01/2018] [Accepted: 01/16/2018] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Calprotectin is a marker of inflammation, but its clinical utility in dogs with chronic inflammatory enteropathies (CIE) is unknown. OBJECTIVE Evaluation of fecal calprotectin in dogs with biopsy-confirmed CIE. ANIMALS 127 dogs. METHODS Prospective case-control study. Dogs were assigned a canine chronic enteropathy clinical activity index (CCECAI) score, and histologic lesions severity was assessed. Fecal calprotectin, fecal S100A12, and serum C-reactive protein (CRP) were measured. Food- or antibiotic-responsive cases (FRE/ARE, n = 13) were distinguished from steroid-/immunosuppressant-responsive or -refractory cases (SRE/IRE, n = 20). Clinical response to treatment in SRE/IRE dogs was classified as complete remission (CR), partial response (PR), or no response (NR). RESULTS Fecal calprotectin correlated with CCECAI (ρ = 0.27, P = .0065) and fecal S100A12 (ρ = 0.90, P < .0001), some inflammatory criteria, and cumulative inflammation scores, but not serum CRP (ρ = 0.16, P = .12). Dogs with SRE/IRE had higher fecal calprotectin concentrations (median: 2.0 μg/g) than FRE/ARE dogs (median: 1.4 μg/g), and within the SRE/IRE group, dogs with PR/NR had higher fecal calprotectin (median: 37.0 μg/g) than dogs with CR (median: 1.6 μg/g). However, both differences did not reach statistical significance (both P = .10). A fecal calprotectin ≥15.2 μg/g separated both groups with 80% sensitivity (95% confidence interval [95%CI]: 28%-100%) and 75% specificity (95%CI: 43%-95%). CONCLUSIONS AND CLINICAL IMPORTANCE Fecal calprotectin could be a useful surrogate marker of disease severity in dogs with CIE, but larger longitudinal studies are needed to evaluate its utility in predicting the response to treatment.
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Affiliation(s)
- Romy M. Heilmann
- Small Animal ClinicCollege of Veterinary Medicine, University of LeipzigLeipzigSaxonyGermany
- Gastrointestinal LaboratoryCollege of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityCollege StationTexas
| | - Nora Berghoff
- Gastrointestinal LaboratoryCollege of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityCollege StationTexas
- Department of Pathobiology & Diagnostic InvestigationCollege of Veterinary Medicine, Michigan State UniversityEast LansingMichigan
| | - Joanne Mansell
- Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityCollege StationTexas
| | - Niels Grützner
- Gastrointestinal LaboratoryCollege of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityCollege StationTexas
- Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle‐WittenbergHalle (Saale)Saxony‐AnhaltGermany
| | - Nolie K. Parnell
- Small Animal Veterinary Teaching Hospital, College of Veterinary Medicine, Purdue UniversityWest LafayetteIndiana
| | - Corinne Gurtner
- Institute of Animal Pathology, Department of Infectious Diseases and PathobiologyVetsuisse Faculty Bern, University of BernBernSwitzerland
- Institute of Veterinary Pathology, College of Veterinary Medicine, Freie Universität BerlinBerlinGermany
| | - Jan S. Suchodolski
- Gastrointestinal LaboratoryCollege of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityCollege StationTexas
| | - Jörg M. Steiner
- Gastrointestinal LaboratoryCollege of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityCollege StationTexas
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Accuracy of Consecutive Fecal Calprotectin Measurements to Predict Relapse in Inflammatory Bowel Disease Patients Under Maintenance With Anti-TNF Therapy: A Prospective Longitudinal Cohort Study. J Clin Gastroenterol 2018; 52:229-234. [PMID: 27984399 DOI: 10.1097/mcg.0000000000000774] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND GOAL Predicting relapse in inflammatory bowel disease (IBD) patients could allow early changes in therapy. We aimed at evaluating the accuracy of consecutive fecal calprotectin (FC) measurements to predict flares in IBD patients under maintenance treatment with anti-tumor necrosis factor (TNF) drugs. STUDY A prospective longitudinal cohort study with 16-month follow-up period was designed. IBD patients in clinical remission for at least 6 months under anti-TNF therapy were included. FC was quantified at 4-month intervals for 1 year, and patients were clinically evaluated for relapse at 2-month intervals. Diagnostic accuracy of FC for predicting relapse was evaluated by receiver-operating characteristic curve analysis. RESULTS In total, 95 of 106 included patients finalized the study and were analyzed (median age 44 y, 50.5% female, 75% with Crohn's disease). A total of 30 patients (31.6%) had a relapse over follow-up. FC concentration was significantly higher in patients who relapsed (477 μg/g) than in patients who maintained in remission (65 μg/g) (P<0.005). The optimal cutoff to predict remission was 130 μg/g (negative predictive value of 100%), and 300 μg/g to predict relapse (positive predictive value of 78.3%). CONCLUSIONS FC is a good predictor of clinical relapse and a particularly good predictor of remission over the following 4 months in patients with IBD on maintenance therapy with anti-TNF drugs. FC levels <130 μg/g is consistently associated with maintained disease remission, whereas concentrations >300 μg/g allow predicting relapse with a high probability at any time over the following 4 months.
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Kaymak T, Moriconi F, Niess JH, Beglinger C, Hruz P. Low Discontinuation Rate of Infliximab Treatment in Steroid-Dependent/Refractory Crohn's Disease Patients. Inflamm Intest Dis 2018; 2:171-179. [PMID: 30018967 DOI: 10.1159/000486676] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 01/03/2018] [Indexed: 12/17/2022] Open
Abstract
Background Many patients with moderate to severe Crohn's disease (CD) are treated with infliximab (IFX). As most of these patients experience a long-lasting therapy, the outcome and withdrawal of IFX treatment are important clinical questions. Methods In this retrospective study, we analyzed the treatment outcome in moderate to severe CD patients with a steroid-dependent/refractory disease course started on IFX. Withdrawal of IFX was evaluated in patients with deep remission defined as clinical (Harvey-Bradshaw Index ≤4), biochemical (fecal calprotectin [FC] ≤150 μg/g stool) over a period of 2 years, and endoscopic and histological remission before discontinuation of IFX. Results After induction with IFX, clinical remission was observed in 45/109 patients (41.3%) and clinical response in 61/109 patients (56.0%). Only 8/109 patients (7.3%) achieved deep remission and therefore could be discontinued from IFX therapy. In 4 of these patients (50%), relapse was observed after discontinuation of IFX treatment. FC decreased in these 8 patients in deep remission from 652 ± 168 μg/g stool (mean ± SE) at baseline to 24.9 ± 8.1 μg/g stool at 14 weeks. When compared to patients in deep remission, FC had decreased significantly less at 14 weeks in patients in clinical remission after induction with IFX (n = 31; 154 ± 55 μg/g stool; p = 0.01), in patients with clinical response after induction achieving clinical remission during the maintenance phase (n = 11; 352 ± 67 μg/g stool; p = 0.004), or in patients with chronic active disease course on maintenance therapy (n = 50; 645 ± 93 μg/g stool; p < 0.001). Conclusion A low discontinuation rate was observed for steroid-dependent/refractory moderate to severe CD patients with IFX treatment. As FC showed a more or less pronounced decrease depending on the response to the IFX treatment, monitoring of FC may become a noninvasive tool for tailoring biological therapy in CD patients.
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Affiliation(s)
- Tanay Kaymak
- Department of Gastroenterology and Hepatology, University Hospital Basel, Basel, Switzerland
| | - Federico Moriconi
- Department of Gastroenterology and Hepatology, Triemli Hospital Zürich, Zürich, Switzerland
| | - Jan H Niess
- Department of Gastroenterology and Hepatology, University Hospital Basel, Basel, Switzerland
| | - Christoph Beglinger
- Department of Gastroenterology and Hepatology, University Hospital Basel, Basel, Switzerland
| | - Petr Hruz
- Department of Gastroenterology and Hepatology, University Hospital Basel, Basel, Switzerland
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Schaefer AK, Melnyk JE, He Z, Del Rosario F, Grimes CL. Pathogen- and Microbial- Associated Molecular Patterns (PAMPs/MAMPs) and the Innate Immune Response in Crohn’s Disease. IMMUNITY AND INFLAMMATION IN HEALTH AND DISEASE 2018:175-187. [DOI: 10.1016/b978-0-12-805417-8.00014-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Chen JM, Liu T, Gao S, Tong XD, Deng FH, Nie B. Efficacy of noninvasive evaluations in monitoring inflammatory bowel disease activity: A prospective study in China. World J Gastroenterol 2017; 23:8235-8247. [PMID: 29290660 PMCID: PMC5739930 DOI: 10.3748/wjg.v23.i46.8235] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Revised: 09/28/2017] [Accepted: 11/01/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To optimize the efficacy of noninvasive evaluations in monitoring the endoscopic activity of inflammatory bowel disease (IBD).
METHODS Fecal calprotectin (FC), clinical activity index (CDAI or CAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT) were measured for 136 IBD patients. Also, FC was measured in 25 irritable bowel syndrome (IBS) patients that served as controls. Then, endoscopic activity was determined by other two endoscopists for colonic or ileo-colonic Crohn’s disease (CICD) with the “simple endoscopic score for Crohn’s disease” (SES-CD), CD-related surgery patients with the Rutgeerts score, and ulcerative colitis (UC) with the Mayo score. The efficacies of these evaluations to predict the endoscopic disease activity were assessed by Mann-Whitney test, χ2 test, Spearman’s correlation, and multiple linear regression analysis.
RESULTS The median FC levels in CD, UC, and IBS patients were 449.6 (IQR, 137.9-1344.8), 497.9 (IQR, 131.7-118.0), and 9.9 (IQR, 049.7) μg/g, respectively (P < 0.001). For FC, CDAI or CAI, CRP, and ESR differed significantly between endoscopic active and remission in CICD and UC patients, but not in CD-related surgery patients. The SES-CD correlated closely with levels of FC (r = 0.802), followed by CDAI (r = 0.734), CRP (r = 0.658), and ESR (r = 0.557). The Mayo score also correlated significantly with FC (r = 0.837), CAI (r = 0.776), ESR (r = 0.644), and CRP (r = 0.634). For FC, a cut-off value of 250 μg/g indicated endoscopic active inflammation with accuracies of 87.5%, 60%, and 91.1%, respectively, for CICD, CD-related surgery, and UC patients. Moreover, clinical FC activity (CFA) calculated as 0.8 × FC + 4.6 × CDAI showed higher area under the curve (AUC) of 0.962 for CICD and CFA calculated as 0.2 × FC + 50 × CAI showed higher AUC (0.980) for UC patients than the FC. Also, the diagnostic accuracy of FC in identifying patients with mucosal inflammation in clinical remission was reflected by an AUC of 0.91 for CICD and 0.96 for UC patients.
CONCLUSION FC is the most promising noninvasive evaluation for monitoring the endoscopic activity of CICD and UC. CFA might be more accurate for IBD activity evaluation.
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Affiliation(s)
- Jin-Min Chen
- Department of Gastroenterology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Tao Liu
- Department of Gastroenterology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510665, Guangdong Province, China
| | - Shan Gao
- Department of Gastroenterology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Xu-Dong Tong
- Department of Gastroenterology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Fei-Hong Deng
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Biao Nie
- Department of Gastroenterology, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510630, Guangdong Province, China
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Conley S, Proctor DD, Jeon S, Sandler RS, Redeker NS. Symptom clusters in adults with inflammatory bowel disease. Res Nurs Health 2017; 40:424-434. [PMID: 28833284 PMCID: PMC5597486 DOI: 10.1002/nur.21813] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Accepted: 06/21/2017] [Indexed: 12/11/2022]
Abstract
Symptoms (pain, fatigue, sleep disturbance, depression, and anxiety) in inflammatory bowel disease (IBD) are associated with reduced quality of life. Understanding how IBD symptoms cluster and the clinical and demographic factors associated with symptom clusters will enable focused development of symptom management interventions. The study purposes were to (i) identify symptom cluster membership among adults with IBD and (ii) examine associations between demographic (age, gender, race/ethnicity, and education) and clinical factors (smoking status, time since diagnosis, medication type, IBD type, disease activity), and membership in specific symptom cluster groups. We conducted a retrospective study of data from the Crohn's and Colitis Foundation of America's (CCFA) Partners Cohort and used Patient Reported Outcome Measurement Information System (PROMIS) measures to measure pain interference, fatigue, sleep disturbance, anxiety, and depression. The sample included 5,296 participants with IBD (mean age 44, 72% female). In latent class analysis (LCA), four groups of participants were identified based on symptoms: "low symptom burden" (26% of sample), "high symptom burden" (38%), "physical symptoms" (22%), and "psychological symptoms" (14%). In multinomial regression, female gender, smoking, corticosteroids, Crohn's disease, and active disease state were associated with membership in the high symptom burden group. Additional research is needed to test interventions that may be effective at reducing symptom burden for individuals with IBD.
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Affiliation(s)
| | - Deborah D Proctor
- Department of Medicine, Section of Digestive Diseases, Yale University, New Haven, CT
| | | | - Robert S. Sandler
- Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC
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Comparative Acceptability and Perceived Clinical Utility of Monitoring Tools: A Nationwide Survey of Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis 2017; 23:1425-1433. [PMID: 28570431 DOI: 10.1097/mib.0000000000001140] [Citation(s) in RCA: 157] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Objective control of intestinal inflammation during inflammatory bowel disease (IBD) is becoming the main driver for medical treatment. However, the monitoring tools-related burden remains poorly investigated. We aimed to evaluate their comparative acceptability and utility according to patients with IBD. METHODS After a preliminary phase, the final questionnaire encompassing self-administered and physician questionnaires was prospectively and consecutively submitted to 916 patients with IBD from 20 public and private centers. Acceptability and utility visual analog scales (VAS) were expressed as median with interquartile range. RESULTS Regarding the group of patients with Crohn's disease (n = 618), venipuncture (VAS = 9.3 [8.8-9.7]) and ultrasonography (VAS = 9.3 [8.7-9.7]) were the most acceptable tools (P < 0.0001, for each comparison), whereas rectosigmoidoscopy was the least acceptable tool (VAS = 4.4 [1.2-7.3]) (P < 0.0001, for each comparison). Wireless capsule endoscopy (VAS = 8.5 [5.2-9.3]), magnetic resonance enterocolonography (VAS = 8.0 [5.0-9.2]), and stools collection (VAS = 7.7 [4.6-9.3]) were more acceptable than colonoscopy (VAS = 6.7 [4.3-8.9]) (P < 0.0001, for each comparison). The acceptability was assessed in 298 patients with ulcerative colitis for venipuncture (VAS = 9.4 [8.8-9.7]), stools collection (VAS = 8.1 [5.7-9.4]), colonoscopy (VAS = 7.5 [4.7-9.2]), and rectosigmoidoscopy (VAS = 6.7 [2.8-9.1]); (P < 0.001 for each comparison). All monitoring tools were considered as highly useful by patients with IBD. Decreased acceptability was related to embarrassment for the collection/transport of stools (60.7%), bowel cleansing (76.3%) for colonoscopy, abdominal discomfort (51.3%) and rectal enema (36.6%) for rectosigmoidoscopy, bowel distension (48.3%) for magnetic resonance enterocolonography, and potential capsule retention (21.4%) for wireless capsule endoscopy. CONCLUSIONS Among the IBD monitoring tools, endoscopy demonstrated the lowest acceptability supporting the development of alternative modalities. Patients' information and examination conditions should be improved to ensure proper monitoring adherence.
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Novak G, Parker CE, Pai RK, MacDonald JK, Feagan BG, Sandborn WJ, D'Haens G, Jairath V, Khanna R. Histologic scoring indices for evaluation of disease activity in Crohn's disease. Cochrane Database Syst Rev 2017; 7:CD012351. [PMID: 28731502 PMCID: PMC6483549 DOI: 10.1002/14651858.cd012351.pub2] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Histologic assessment of mucosal disease activity has been increasingly used in clinical trials of treatment for Crohn's disease. However, the operating properties of the currently existing histologic scoring indices remain unclear. OBJECTIVES A systematic review was undertaken to evaluate the development and operating characteristics of available histologic disease activity indices in Crohn's disease. SEARCH METHODS Electronic searches of MEDLINE, EMBASE, PubMed, and the Cochrane Library (CENTRAL) databases from inception to 20 July 2016 were supplemented by manual reviews of bibliographies and abstracts submitted to major gastroenterology meetings (Digestive Disease Week, United European Gastroenterology Week, European Crohn's and Colitis Organisation). SELECTION CRITERIA Any study design (e.g. randomised controlled trial, cohort study, case series) that evaluated a histologic disease activity index in patients with Crohn's disease was considered for inclusion. Study participants included adult patients (> 16 years), diagnosed with Crohn's disease using conventional clinical, radiographic or endoscopic criteria. DATA COLLECTION AND ANALYSIS Two authors independently reviewed the titles and abstracts of the studies identified from the literature search. The full text of potentially relevant citations were reviewed for inclusion and the study investigators were contacted as needed for clarification. Any disagreements regarding study eligibility were resolved by discussion and consensus with a third author.Two authors independently extracted and recorded data using a standard form. The following data were recorded from each eligible study: number of patients enrolled; number of patients per treatment arm; patient characteristics: age and gender distribution; description of histologic disease activity index utilized; and outcomes such as content validity, construct validity, criterion validity, responsiveness, intra-rater reliability, inter-rater reliability, and feasibility. MAIN RESULTS Sixteen reports of 14 studies describing 14 different numerical histological indices fulfilled the inclusion criteria.Inter-rater reliability was assessed in one study. For the Naini and Cortina Score, estimates of correlation were 'almost perfect', ranging from r = 0.94 to 0.96. The methodological quality of this study with respect to reliability was 'good'.With respect to validity, correlation estimates between various histological scoring systems and Crohn's disease activity as measured by objective markers of inflammation (including C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin and fecal lactoferrin); endoscopic disease activity scores; clinical disease activity scores; and quality of life questionnaires were reported. Comparisons between histologic scoring indices and endoscopic scoring indices ranged from no correlation to 'substantial' (r = 0.779). The methodological quality of the studies that explored validity ranged form 'poor' to 'good'.Responsiveness data were available in seven studies. After subjects were administered a treatment of known efficacy, statistically significant change in the index score was demonstrated in five studies with respect to six indices. Two studies failed to indicate whether there was statistically significant change in the index score post-treatment. With regard to methodological quality, six of the studies were rated as 'poor' and one of the studies was rated as 'fair'.Feasibility was assessed by one study. The Naini and Cortina Score was shown to be simple to use and feasible for every given case. AUTHORS' CONCLUSIONS Currently there is no fully validated histological scoring index for evaluation of Crohn's disease activity. Development of a validated histological scoring index for Crohn's disease is a clinical and research priority.
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Affiliation(s)
- Gregor Novak
- Academic Medical Center, University of AmsterdamDepartment of GastroenterologyAmsterdamNetherlands
- University Medical CentreDepartment of Gastroenterology and HepatologyLjubljanaSlovenia
| | - Claire E Parker
- Robarts Clinical Trials100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
| | - Rish K Pai
- Mayo ClinicDepartment of PathologyScottsdaleAZUSA
| | - John K MacDonald
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
- University of Western OntarioDepartment of MedicineLondonONCanada
| | - Brian G Feagan
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
- University of Western OntarioDepartment of MedicineLondonONCanada
- University of Western OntarioDepartment of Epidemiology and BiostatisticsLondonONCanada
| | - William J Sandborn
- University of California San DiegoDivision of GastroenterologyLa JollaCAUSA
| | - Geert D'Haens
- Academic Medical CenterMeibergdreef 9 ‐ C2‐112AmsterdamNetherlands1105 AZ
- Robarts Clinical TrialsAmsterdamNetherlands
| | - Vipul Jairath
- University of Western OntarioDepartment of MedicineLondonONCanada
- University of Western OntarioDepartment of Epidemiology and BiostatisticsLondonONCanada
| | - Reena Khanna
- Robarts Clinical Trials100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
- University of Western OntarioDepartment of MedicineLondonONCanada
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Fu Y, Wang L, Xie C, Zou K, Tu L, Yan W, Hou X. Comparison of non-invasive biomarkers faecal BAFF, calprotectin and FOBT in discriminating IBS from IBD and evaluation of intestinal inflammation. Sci Rep 2017; 7:2669. [PMID: 28572616 PMCID: PMC5453945 DOI: 10.1038/s41598-017-02835-5] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 04/19/2017] [Indexed: 12/13/2022] Open
Abstract
Faecal calprotectin and faecal occult blood test (FOBT) were widely used in the diagnosis and assessment of intestinal inflammation in inflammatory bowel disease (IBD). Recently we identified an excellent new biomarker B cell-activating factor (BAFF) for IBD. Here in this study we compared the efficacy of faecal BAFF, calprotectin and FOBT to find the “best non-invasive marker”. Results showed that for discriminating IBD from IBS, BAFF ≥227.3 pg/ml yield 84% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 64% negative predictive value (NPV) while calprotectin ≥50 µg/g yield 76% sensitivity, 93% specificity, 97% PPV and 53% NPV. FOBT yield 65% sensitivity, 93% specificity, 97% PPV and 43% NPV. Combining BAFF with calprotectin tests yield 94% sensitivity, 93% specificity, 98% PPV, 81% NPV. Faecal BAFF level showed the stronger correlation with endoscopic inflammatory score as compared to calprotectin not only in UC (correlation coefficient [r] = 0.69, p < 0.0001 vs. r = 0.58, p < 0.0001), but also in CD (r = 0.58, p < 0.0001 vs. r = 0.52, p = 0.0003). Our results indicating that faecal BAFF is a promising non-invasive biomarker in IBD differential diagnosis and monitoring of intestinal inflammation.
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Affiliation(s)
- Yu Fu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China
| | - Lingli Wang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China
| | - Cheng Xie
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China
| | - Kaifang Zou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China
| | - Lei Tu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China
| | - Wei Yan
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
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Kalappurayil NB, Thomas J, Mankuni B, Thomas V. Assessment of Disease Severity and Role of Cytomegalo Virus Infection in Patients with Ulcerative Colitis. J Clin Diagn Res 2017; 11:EC07-EC11. [PMID: 28511386 DOI: 10.7860/jcdr/2017/22816.9332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Accepted: 10/20/2016] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Course of Ulcerative Colitis is characterized by intermittent flares interposed between variable periods of remission. Identification of exacerbating factors and appropriate assessment of disease activity are crucial in deciding the choice of treatment. AIM To evaluate various clinical, endoscopic and histological parameters in assessing disease activity and to find out various risk factors involved in the exacerbation of ulcerative colitis especially the role of Cytomegalo Virus (CMV) infection. MATERIALS AND METHODS It was a prospective study of patients diagnosed as ulcerative colitis presenting with acute exacerbation of symptoms (cases) and those who were in remission (controls). A detailed evaluation of the disease history including personal history, treatment compliance and clinical disease severity were noted. Investigations including blood routine, endoscopic examination with biopsy, histopathological examination and immunohistochemistry for CMV were done on the biopsy sample. RESULTS A total of 58 patients with ulcerative colitis were studied which included 37 cases and 21 controls. Out of the various clinical and demographic parameters, Good treatment compliance (p =0.0003) and Perceived Stress Scale (PSS) score (p=0.0001) showed significant difference between cases and controls. Basic laboratory parameters {Haemoglobin level, Total Leucocyte Count (TLC) and Erythrocyte Sedimentation Rate (ESR)}, clinical disease severity predictors (Truelove and Witt's criteria, Mayo score and endoscopic disease severity grade) and Geboes histological scoring showed significant difference between cases and controls. The prevalence of CMV colitis in our study was only 5.4% (two cases). CONCLUSION Clinical and endoscopic disease severity indicators can be used as predictors of histological activity in ulcerative colitis. Poor treatment compliance and stress are important risk factors for acute exacerbation of ulcerative colitis. Clinicians should be aware of the possibility of concurrent CMV infection while treating patients with acute exacerbation of ulcerative colitis not responding to the conventional management. Reduced prevalence of CMV colitis in cases of acute exacerbation of ulcerative colitis in our study may be due to the small sample size, reduced number of steroid dependent cases or reduced severity of our cases.
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Affiliation(s)
- Nobin Babu Kalappurayil
- Assistant Professor, Department of General Pathology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Jino Thomas
- Consultant, Department of Gastroenterology, Caritas Hospital, Kottayam, Kerala, India
| | - Baburajan Mankuni
- Associate Professor, Department of Pathology, Government Medical College, Idukki, Kerala, India
| | - Varghese Thomas
- Professor, Department of Gastroenterology, Government Medical College, Kozhikode, Kerala, India
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Yamamoto-Furusho J, Bosques-Padilla F, de-Paula J, Galiano M, Ibañez P, Juliao F, Kotze P, Rocha J, Steinwurz F, Veitia G, Zaltman C. Diagnosis and treatment of inflammatory bowel disease: First Latin American Consensus of the Pan American Crohn's and Colitis Organisation. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2017. [DOI: 10.1016/j.rgmxen.2016.07.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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Frin AC, Filippi J, Boschetti G, Flourie B, Drai J, Ferrari P, Hebuterne X, Nancey S. Accuracies of fecal calprotectin, lactoferrin, M2-pyruvate kinase, neopterin and zonulin to predict the response to infliximab in ulcerative colitis. Dig Liver Dis 2017; 49:11-16. [PMID: 27693318 DOI: 10.1016/j.dld.2016.09.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Revised: 09/02/2016] [Accepted: 09/03/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Fecal markers might predict the response to anti-TNFα in ulcerative colitis (UC). AIMS To compare the performance of fecal calprotectin (fCal), lactoferrin (fLact), M2-PK (fM2-PK), neopterin (fNeo), and zonulin (fZon) to predict the response to therapy in active UC patients. METHODS Disease activity from 31 consecutive patients with an active UC, treated with infliximab (IFX) was assessed by the Mayo score at baseline and at week 14 and by the partial Mayo score at W52 and stool samples collected for fecal marker measurements at W0, W2, and W14. RESULTS At W14, 19 patients (61%) were responders to IFX induction. The median levels of fCal, fLact and fM2-PK drop dramatically from baseline to W14 in clinical responders. At W2, fM2-PK, fLact and fCal levels predicted accurately the response to IFX induction. At W14, fLact, fCal, and fM2-PK were individually reliable markers to predict sustained response at W52. The performances of fNeo and fZon were weaker in this setting. CONCLUSIONS The performance of fM2-PK at W2 to predict response to induction therapy with IFX was superior to that of fLact and fCal, whereas monitoring fLact was the best tool to predict adequately the course of the disease at one year under maintenance IFX in UC.
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Affiliation(s)
- Anne-Claire Frin
- Department of Gastroenterology, Centre Hospitalier Universitaire L'Archet, Nice, France
| | - Jérôme Filippi
- Department of Gastroenterology, Centre Hospitalier Universitaire L'Archet, Nice, France
| | - Gilles Boschetti
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre-Bénite, France & INSERM U1111, International Center for Research in Infectiology, Lyon, France
| | - Bernard Flourie
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre-Bénite, France & INSERM U1111, International Center for Research in Infectiology, Lyon, France
| | - Jocelyne Drai
- Laboratory of Biochemistry, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre-Bénite, France
| | - Patricia Ferrari
- Laboratory of Biochemistry, Centre Hospitalier Universitaire Pasteur, Nice, France
| | - Xavier Hebuterne
- Department of Gastroenterology, Centre Hospitalier Universitaire L'Archet, Nice, France
| | - Stéphane Nancey
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre-Bénite, France & INSERM U1111, International Center for Research in Infectiology, Lyon, France.
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Abraham BP, Ahmed T, Ali T. Inflammatory Bowel Disease: Pathophysiology and Current Therapeutic Approaches. Handb Exp Pharmacol 2017; 239:115-146. [PMID: 28233184 DOI: 10.1007/164_2016_122] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Inflammatory bowel diseases, most commonly categorized as Crohn's disease and ulcerative colitis, are immune mediated chronic inflammatory disorders of the gastrointestinal tract. The etiopathogenesis is multifactorial with different environmental, genetic, immune mediated, and gut microbial factors playing important role. The current goals of therapy are to improve clinical symptoms, control inflammation, prevent complications, and improve quality of life. Different therapeutic agents, with their indications, mechanisms of action, and side effects are discussed in this chapter. Anti-integrin therapy, a newer therapeutic class, with its potential beneficial role in both Crohn's disease and ulcerative colitis is also mentioned. In the end, therapeutic algorithms for both diseases are reviewed.
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Affiliation(s)
- Bincy P Abraham
- Houston Methodist Hospital/Weill Cornell Medical College, Houston, TX, USA
| | | | - Tauseef Ali
- University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
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Yamamoto-Furusho JK, Bosques-Padilla F, de-Paula J, Galiano MT, Ibañez P, Juliao F, Kotze PG, Rocha JL, Steinwurz F, Veitia G, Zaltman C. Diagnosis and treatment of inflammatory bowel disease: First Latin American Consensus of the Pan American Crohn's and Colitis Organisation. REVISTA DE GASTROENTEROLOGIA DE MEXICO 2017; 82:46-84. [PMID: 27979414 DOI: 10.1016/j.rgmx.2016.07.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/20/2016] [Revised: 06/23/2016] [Accepted: 07/06/2016] [Indexed: 02/08/2023]
Abstract
The incidence and prevalence of inflammatory bowel disease (IBD) has increased in recent years in several Latin American countries. There is a need to raise awareness in gastroenterologists and the population in general, so that early diagnosis and treatment of ulcerative colitis (UC) and Crohn's Disease (CD) can be carried out. It is important for all physicians to have homogeneous criteria regarding the diagnosis and treatment of IBD in Latin America. The Pan American Crohn's and Colitis Organisation (PANCCO) is an organization that aims to include all the countries of the Americas, but it specifically concentrates on Latin America. The present Consensus was divided into two parts for publication: 1) Diagnosis and treatment and 2) Special situations. This is the first Latin American Consensus whose purpose is to promote a perspective adapted to our Latin American countries for the diagnosis, treatment, and monitoring of patients with UC and CD.
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Affiliation(s)
- J K Yamamoto-Furusho
- Clínica de Enfermedad Inflamatoria Intestinal, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México.
| | - F Bosques-Padilla
- Gastroenterology Division, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México; Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, México
| | - J de-Paula
- Servicio de Gastroenterología, Hospital Italiano, Buenos Aires, Argentina
| | - M T Galiano
- Clínica de Enfermedad Inflamatoria Intestinal, Clínica Marly, Bogotá, Colombia
| | - P Ibañez
- Programa de Enfermedad Inflamatoria Intestinal, Departamento de Gastroenterología, Clínica Las Condes, Santiago, Chile
| | - F Juliao
- Clínica de Enfermedad Inflamatoria Intestinal, Hospital Pablo Tobón Uribe, Medellín, Colombia
| | - P G Kotze
- Hospital Universitario Cajuru, Universidad Católica del Paraná (PUCPR), Curitiba, Brasil
| | - J L Rocha
- Grupo Académico y de Investigación sobre Enfermedad de Crohn y Colitis Ulcerosa Crónica Idiopática de México, Ciudad de México, México
| | - F Steinwurz
- Hospital Israelita Albert Einstein, São Paulo, Brasil
| | - G Veitia
- Servicio de Gastroenterología, Hospital Vargas, Caracas, Venezuela
| | - C Zaltman
- Servicio de Gastroenterología, Hospital Clementino Fraga Filho, Departamento de Medicina Interna, Universidade Federal do Rio de Janeiro (UFRJ), Río de Janeiro, Brasil
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Hukkinen M, Pakarinen MP, Merras-Salmio L, Koivusalo A, Rintala R, Kolho KL. Fecal calprotectin in the prediction of postoperative recurrence of Crohn's disease in children and adolescents. J Pediatr Surg 2016; 51:1467-72. [PMID: 26891835 DOI: 10.1016/j.jpedsurg.2016.01.017] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Revised: 01/09/2016] [Accepted: 01/09/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Fecal calprotectin (FC) correlates with endoscopic recurrence of Crohn's disease (CD) in adults but has not been studied among children postoperatively. We aimed to analyze whether FC relates with postoperative CD recurrence in children. METHODS Altogether 51 postoperative endoscopies and FC measurements from 22 patients having undergone surgery for CD at age ≤18years were included. RESULTS Ileocecal resection (n=15), small bowel resection (n=6), or left hemicolectomy (n=1) was performed at median age of 15.1 (interquartile range 14.4-17.6) years. Following surgery, FC decreased significantly (659 vs. 103μg/g, p=0.001). During median follow-up of 5.7 (4.2-7.7) years, either endoscopic or histological recurrence occurred in 17 patients (77%). FC >139μg/g at time of endoscopy or FC increase of 79μg/g compared to first postoperative value was suggestive of endoscopic recurrence (Rutgeerts score i2-i4), while FC >101μg/g or increase of 21μg/g indicated histological recurrence. Best accuracy for prediction of recurrence was obtained by combining FC at endoscopy and the postoperative increase of FC. The corresponding AUROC values were 0.74 (95% 0.58-0.89) for endoscopic recurrence whereas 0.81 (95% CI 0.67-0.95) for histological recurrence. CONCLUSION FC is a useful surrogate marker of postoperative recurrence also in pediatric CD patients.
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Affiliation(s)
- Maria Hukkinen
- Pediatric Liver and Gut Research Group, Children's Hospital, University of Helsinki, Finland.
| | - Mikko P Pakarinen
- Pediatric Liver and Gut Research Group, Children's Hospital, University of Helsinki, Finland; Section of Pediatric Surgery, Children's Hospital, University of Helsinki, Finland
| | - Laura Merras-Salmio
- Pediatric Liver and Gut Research Group, Children's Hospital, University of Helsinki, Finland; Section of Pediatric Gastroenterology, Children's Hospital, University of Helsinki, Finland
| | - Antti Koivusalo
- Section of Pediatric Surgery, Children's Hospital, University of Helsinki, Finland
| | - Risto Rintala
- Section of Pediatric Surgery, Children's Hospital, University of Helsinki, Finland
| | - Kaija-Leena Kolho
- Section of Pediatric Gastroenterology, Children's Hospital, University of Helsinki, Finland
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Khanna R, Nelson SA, Feagan BG, D'Haens G, Sandborn WJ, Zou GY, MacDonald JK, Parker CE, Jairath V, Levesque BG. Endoscopic scoring indices for evaluation of disease activity in Crohn's disease. Cochrane Database Syst Rev 2016; 2016:CD010642. [PMID: 27501379 PMCID: PMC7079710 DOI: 10.1002/14651858.cd010642.pub2] [Citation(s) in RCA: 26] [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] [Indexed: 12/26/2022]
Abstract
BACKGROUND Endoscopic assessment of mucosal disease activity is widely used to determine eligibility and response to therapy in clinical trials of treatment for Crohn's disease. However, the operating properties of the currently available endoscopic indices remain unclear. OBJECTIVES A systematic review was undertaken to evaluate the development and operating characteristics of the Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simple Endoscopic Scale for Crohn's Disease (SES-CD). SEARCH METHODS Electronic searches of the MEDLINE (1966 to December 2015), EMBASE (1980 to December 2015), and Cochrane CENTRAL Register of Controlled Trials (Issue 12, 2015) databases were supplemented by manual reviews of reference listings and conference proceedings (Digestive Disease Week, United European Gastroenterology Week, European Crohn's and Colitis Organization). SELECTION CRITERIA Any study design (e.g. randomized controlled trials, cohort studies, case series) that evaluated either or both the CDEIS or SES-CD in patients with Crohn's disease was considered for inclusion. Eligible participants were adult patients (> 16 years), diagnosed with Crohn's disease using conventional clinical, radiographic, and endoscopic criteria. DATA COLLECTION AND ANALYSIS Two authors (RK, JKM) independently reviewed the titles and abstracts of the studies identified from the literature search. The full texts of potentially relevant citations were reviewed for inclusion and the study investigators were contacted to clarify any unclear data. Any disagreements were resolved by discussion and consensus with a third author. A standardized form was used to assess eligibility of trials for inclusion in the study and for data extraction.Two authors independently extracted and recorded data (RK, SAN). The number of patients enrolled; number of patients per treatment arm; patient characteristics including age and gender distribution; endoscopic index; and outcomes such as intra-rater reliability, inter-rater reliability responsiveness, validity, feasibility, construct validity, and criterion validity were recorded for each trial. MAIN RESULTS Forty-three reports of 30 studies fulfilled the inclusion criteria.For the SES-CD, inter-rater reliability was assessed in four studies. In the development study for the SES-CD (Daperno 2004), the overall ICC (0.9815, 95% CI 0.9705 to 0.9884) and the kappa for the regions is high; however the paired raters were in the same room which introduces the potential for bias.For the CDEIS, inter-rater reliability was assessed in six studies. Daperno 2014 reported that the ICC for the CDEIS was 0.985 (95% CI 0.939-1.000) for average measures of video score and was 0.835 (95% CI 0.540-0.995) for single measures of video score.With respect to validity, correlation between the CDEIS and clinical measures, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), was also reported. The estimates of correlation with CRP were r = 0.521 (Sipponen 2010b), r = 0.553 (Sipponen 2008a) and r = 0.608 (Sipponen 2008c). For the SES-CD, the corresponding values for correlation with CRP ranged from r = 0.46 (Jones 2008) to r = 0.68 (Green 2011).Responsiveness data for the CDEIS were available in nine studies. Seven studies demonstrated statistically significant decreases in the CDEIS score after administration of a treatment of known efficacy. Minimal responsiveness data were available for the SES-CD. Sipponen 2010a and Sipponen 2010b demonstrated statistically significant changes in the SES-CD score after subjects were administered a treatment of known efficacy.No studies were identified that explicitly evaluated the feasibility for either the SES-CD or the CDEIS. The SES-CD requires fewer calculations and may therefore be easier to use than the CDEIS. AUTHORS' CONCLUSIONS Although they are used in clinical trials, the CDEIS and SES-CD remain incompletely validated. Future research is required to determine the operating properties and to define the optimal index.
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Affiliation(s)
- Reena Khanna
- University of Western OntarioDepartment of MedicineLondonONCanada
- Robarts Clinical TrialsLondonONCanada
| | | | - Brian G Feagan
- University of Western OntarioDepartment of MedicineLondonONCanada
- Robarts Clinical TrialsLondonONCanada
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
- University of Western OntarioDepartment of Epidemiology and BiostatisticsLondonONCanada
| | - Geert D'Haens
- Academic Medical CenterMeibergdreef 9 ‐ C2‐112AmsterdamNetherlands1105 AZ
- Robarts Clinical TrialsAmsterdamNetherlands
| | - William J Sandborn
- Robarts Clinical TrialsSan DiegoCAUSA
- University of California San DiegoDivision of GastroenterologyLa JollaCAUSA
| | - GY Zou
- Robarts Clinical TrialsLondonONCanada
- University of Western OntarioDepartment of Epidemiology and BiostatisticsLondonONCanada
| | - John K MacDonald
- University of Western OntarioDepartment of MedicineLondonONCanada
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
| | | | - Vipul Jairath
- University of Western OntarioDepartment of MedicineLondonONCanada
- Robarts Clinical TrialsLondonONCanada
- University of Western OntarioDepartment of Epidemiology and BiostatisticsLondonONCanada
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Morita Y, Bamba S, Takahashi K, Imaeda H, Nishida A, Inatomi O, Sasaki M, Tsujikawa T, Sugimoto M, Andoh A. Prediction of clinical and endoscopic responses to anti-tumor necrosis factor-α antibodies in ulcerative colitis. Scand J Gastroenterol 2016; 51:934-41. [PMID: 26888161 DOI: 10.3109/00365521.2016.1144781] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objective In patients with ulcerative colitis (UC), the relationship between the initial endoscopic findings and the response to anti-tumor necrosis factor (TNF)-α antibodies remains unclear. We herein evaluated the potential of endoscopic assessment using the ulcerative colitis endoscopic index of severity (UCEIS) to predict the response to anti-TNF-α antibodies. Methods We enrolled 64 patients with UC undergoing anti-TNF-α maintenance therapy with infliximab (IFX) or adalimumab (ADA) between April 2010 and March 2015. Anti-TNF-α trough levels were determined by ELISA. Endoscopic disease activity was assessed using the UCEIS. Results The clinical response rate at 8 weeks was 77.4% for IFX and 66.7% for ADA. Serum albumin levels were significantly higher and the UCEIS bleeding descriptor before treatment was significantly lower in the responders than in the non-responders (p < 0.05 each). The CRP levels at 2 weeks were significantly lower in the responders (p < 0.001). The serum albumin levels before treatment were significantly higher and the UCEIS erosions and ulcers descriptor was significantly lower in the mucosal healing group than in the non-mucosal healing group (p < 0.05 each). A significant and negative correlation between the trough levels of anti-TNF-α antibodies and the UCEIS descriptors was observed. The trough levels of anti-TNF-α antibodies to achieve mucosal healing were 2.7 μg/mL for IFX and 10.3 μg/mL for ADA. Conclusions The UCEIS score, as well as some clinical markers (serum albumin and CRP levels), is useful for the prediction of the treatment outcome of UC patients in response to anti-TNF-α antibodies.
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Affiliation(s)
- Yukihiro Morita
- a Department of Medicine , Shiga University of Medical Science , Otsu , Japan
| | - Shigeki Bamba
- a Department of Medicine , Shiga University of Medical Science , Otsu , Japan
| | - Kenichiro Takahashi
- a Department of Medicine , Shiga University of Medical Science , Otsu , Japan
| | - Hirotsugu Imaeda
- a Department of Medicine , Shiga University of Medical Science , Otsu , Japan
| | - Atsushi Nishida
- a Department of Medicine , Shiga University of Medical Science , Otsu , Japan
| | - Osamu Inatomi
- a Department of Medicine , Shiga University of Medical Science , Otsu , Japan
| | - Masaya Sasaki
- b Division of Clinical Nutrition , Shiga University of Medical Science , Otsu , Japan
| | - Tomoyuki Tsujikawa
- c Department of Comprehensive Internal Medicine , Shiga University of Medical Science , Otsu , Japan
| | - Mitsushige Sugimoto
- a Department of Medicine , Shiga University of Medical Science , Otsu , Japan
| | - Akira Andoh
- a Department of Medicine , Shiga University of Medical Science , Otsu , Japan
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Elsaadany HM, Almaghraby MF, Edrees AA, Elsherbiny YM, Kumar RK. Utility of fecal calprotectin as a discriminative biomarker between ulcerative colitis and irritable bowel syndrome and its ability to be used for the assessment of the remission stage of ulcerative colitis. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2016. [DOI: 10.4103/1110-7782.182956] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
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