Application of Artificial Intelligence Modeling Technology Based on Multi-Omics in Noninvasive Diagnosis of Inflammatory Bowel Disease

Preclinical IBD: One more piece of the puzzle

Objective This study is designed to evaluate the role of fecal calprotectin as a marker for the diagnosis of ulcerative colitis (UC) and its correlation with disease activity and remission. Background Inflammatory bowel diseases (IBD) are lifelong intestinal inflammatory conditions of unknown etiology, characterized by remissions and exacerbations. The diagnosis and classification of IBD is usually established by a combination of tests (laboratory, endoscopic, and/or radiologic) in the presence of clinical symptoms. Fecal calprotectin serves as a noninvasive biomarker of intestinal inflammation, and has been found to be useful in the diagnosis of IBD, assessment of response to medical therapy, and in prediction of clinical relapse. Materials and methods This study was carried out on 40 patients. Twenty of these patients had clinical, laboratory, colonoscopic, and histopathological findings of UC. Group I was subdivided as follows: GIa: 20 patients with active UC and GIb: the same patients as in GIa while on remission. Group II included 20 patients as controls, matched for age and sex without clinical, laboratory, colonoscopic, and histopathological findings of UC. Complete stool analysis, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) titer, complete blood count, colonoscopy and biopsy, histopathological examination of biopsy specimens, measurement of ulcerative colitis activity index (UCAI), and quantitative determination of calprotectin in stool sample were carried out for all patients. Results There was a highly significant increase in the mean value of fecal calprotectin in active UC patients in comparison with the inactive UC patients and controls. Also, there was a highly significant increase in the mean value of fecal calprotectin in the inactive UC patients in comparison with the controls. There was also a highly significant positive correlation between fecal calprotectin and UCAI, CRP, ESR, total leukocyte count, and platelets count. At the cut-off value of 131 μg/g, fecal calprotectin has 100% accuracy, sensitivity, specificity, positive predictive value, and negative predictive value in differentiating UC patients from other patients with lower gastrointestinal symptoms and at the cut-off value of 253 μg/g fecal calprotectin has 95% accuracy, sensitivity, specificity, positive predictive value, and negative predictive value in differentiating active from inactive UC patients. Conclusion Fecal calprotectin is a valuable, simple, easily performed, and cost-effective noninvasive marker for evaluation of patients with UC. It differentiated UC and other diseases causing colonic symptoms (cut-off value of 131 μg/g) and between active and inactive UC (cut-off value of 235 μg/g) with high accuracy, sensitivity, and specificity. It also correlates well with other markers for UC activity (UCAI, ESR, CRP, total leukocyte count, and platelets count) and could be a reliable surrogate marker for the severity of UC.

Aim Faecal calprotectin (FC) is increasingly used as a marker of intestinal inflammation, especially in diagnosis of inflammatory bowel disease (IBD). A meta-analysis (Rheenen et al . BMJ 2010) evaluated adult and paediatric studies to October 2009 and concluded that FC has good discriminative power to safely exclude IBD. However, the seven paediatric studies only included a total of 226 paediatric IBD (PIBD) patients, therefore small study effect may have existed. We aimed to determine the usefulness of FC at presentation in children with suspected IBD by evaluating all the available literature. Methods A search was performed with keywords relating to IBD and calprotectin in several electronic resources from 1966 to November 2011. A hand search of articles was also performed, drawn from reference lists and meeting abstracts. Inclusion criteria were studies that reported FC levels prior to the endoscopic investigation of IBD in children less than 18 years old. There was no English language restriction. Each study was evaluated using the QUADAS tool and a meta-analysis of all included studies was performed using RevMan (v 5.1) and HSROC (R package). Pooled sensitivity and specificity was generated using a random effects model. Results A total of 73 papers were identified during the initial search. All were reviewed but only 8 met the inclusion criteria (6 prospective and 2 retrospective case-control studies). Two studies in the original BMJ meta-analysis (Bunn 2001, Kolho 2006) were excluded as both the IBD and control groups did not represent children undergoing primary investigation for suspected IBD. In total the studies presented FC levels at presentation in 394 IBD patients and 353 non-IBD controls. Pooled specificity and sensitivity for the diagnostic utility of FC during the investigation of suspected PIBD were 0.998 (95% CI 0.960-1.000) and 0.665 (95% CI 0.537-0.820) respectively. Conclusions FC has a high specificity but a modest specificity for the diagnosis of IBD in the paediatric population. The inclusion of two new larger studies and removal of two studies from the original meta-analysis led to an increase in the pooled sensitivity and reduction in pooled specificity. Furthermore, it is evident from other studies that use of a higher normal range (i.e. >200 ug/g) would significantly increase this specificity and therefore further work is required that report multiple cut off levels to truly appreciate the value of this test.

Background Faecal calprotectin has been shown to be a useful non-invasive marker for the diagnosis and monitoring of inflammatory bowel disease in children and adults. Although there are well-established reference ranges for the diagnosis of inflammatory bowel disease in adults, these have been less well studied in children. The objective was to establish reference ranges in our local population. Method All faecal calprotectin results from 2011 to 2014 were retrospectively collated and grouped according to patient age. Probability plots were used to determine expected upper limit of normal for each age group, and Mann-Whitney test was used to determine statistical difference between groups. Results Upper limit of normal for age groups 1-3.9 years, 4-17.9 years and 18 years plus were 77, 62 and 61 µg/g, respectively. There was a significant difference ( P = 0.0013) between the median calprotectin concentration for the age group 1-3.9 years ( n = 87) and 4-17.9 years ( n = 636) and between the age group 1-3.9 years and 18 years plus ( n = 7953, P = 0.0001), but there was no significant difference between the age groups 4-17.9 years and 18 years plus ( P = 0.4206). Conclusions In our local population, faecal calprotectin varies with age. Children aged 1-3.9 years had higher concentrations of faecal calprotectin than adults, but there was no significant difference in faecal calprotectin between older children and adults. This is in agreement with other published studies; however, the faecal calprotectin upper limit of normal calculated for children aged 1-3.9 years was lower than has been observed elsewhere.

BackgroundIt is estimated that between 5% and 10% of patients with spondyloarthritis (SpA) are associated with inflammatory bowel disease (IBD). It has also been proven through endoscopic and histological studies...

P232 Evaluation of the use of fecal calprotectin as a diagnostic aid for IBD in an Irish population

P233 Early measurement of fecal calprotectin after intestinal resection is useful to predict postoperative recurrence in patients with Crohn's disease

AGA Clinical Practice Update on Management of Inflammatory Bowel Disease in Elderly Patients: Expert Review

Faecal calprotectin (FC) is a neutrophil-derived protein released in stool in response to mucosal inflammation. It is a simple, cheap and non-invasive test with high sensitivity and moderate specificity, which...

There is currently no single test available to confidently diagnose cases of inflammatory bowel disease (IBD). Physicians rely on a number of diagnostic tools, including clinical evaluation, serum testing, and imaging, which are used on conjunction with endoscopic evaluation. It is often difficult to determine whether patients with abdominal pain and change in bowel habit have functional bowel symptoms or whether they have a true diagnosis of IBD. Even once a diagnosis of IBD has been made, a significant proportion of patients are labeled with the term "indeterminate colitis" where histological sampling cannot confidently subclassify patients as either Crohn's or ulcerative colitis. Colonoscopy is an inconvenient and uncomfortable test for most patients. In addition, it is not without serious risks of perforation, as well as risks which can be associated with sedation and analgesia given during the procedure. The use of biomarkers to aid in the diagnosis, subclassification, and monitoring of IBD is an ever expanding area. In this review, we have concentrated on noninvasive biomarkers of IBD, because these are more acceptable to patients and easier to perform in everyday clinical practice. We will first touch on those biomarkers currently well established and in wide clinical use, such as C-reactive protein, erythrocyte sedimentation rate. Faecal calprotectin and their use in the diagnosis of IBD. Following on, we will review more novel biomarkers and their use in subclassification and monitoring of IBD, including a variety of antibodies, genetics, and microRNAs, as well as touching on metabolomics.

There is currently no gold standard test for the diagnosis of inflammatory bowel disease (IBD). Physicians must rely on a number of diagnostic tools including clinical and endoscopic evaluation as well as histologic, serologic and radiologic assessment. The real difficulty for physicians in both primary and secondary care is differentiating between patients suffering from functional symptoms and those with true underlying IBD. Alongside this, there is always concern regarding the possibility of a missed, or delayed diagnosis of ulcerative colitis (UC) or Crohn's disease. Even once the diagnosis of IBD has been made, there is often uncertainty in distinguishing between cases of UC or Crohn's. As a consequence, in cases of incorrect diagnosis, optimal treatment and management may be adversely affected. Endoscopic evaluation can be uncomfortable and inconvenient for patients. It carries significant risks including perforation and in terms of monetary cost, is expensive. The use of biomarkers to help in the diagnosis and differentiation of IBD has been increasing over time. However, there is not yet one biomarker, which is sensitive of specific enough to be used alone in diagnosing IBD. Current serum testing includes C-reactive protein and erythrocyte sedimentation rate, which are cheap, reliable but non-specific and thus not ideal. Stool based testing such as faecal calprotectin is a much more specific tool and is currently in widespread clinical use. Non-invasive sampling is of the greatest clinical value and with the recent advances in metabolomics, genetics and proteomics, there are now more tools available to develop sensitive and specific biomarkers to diagnose and differentiate between IBD. Many of these new advances are only in early stages of development but show great promise for future clinical use.

<h3>Introduction</h3> Faecal calprotectin is extremely sensitive to gut inflammation, and as such, is less sensitive to the diagnosis of inflammatory bowel disease (IBD) in patients presenting with acute symptoms. Local guidelines suggest faecal calprotectin test to be performed in patients between the ages of 18 and 50, with lower gastrointestinal symptoms with loose stools for longer than four weeks. <h3>Methods</h3> All inpatient faecal calprotectin requests in 2019 at the Royal Glamorgan Hospital (RGH) were obtained. Data collection included patient identifiable number, request indication, faecal calprotectin level, current IBD status, presenting symptom, if endoscopy was conducted and if a new diagnosis of IBD was made. <h3>Results</h3> There were 63 inpatients who had faecal calprotectin tests performed, of which 44 were adult patients (&gt;18-year-old). Only adult patients were included in this study. The patients were categorized into faecal calprotectin level groups. Four patients(9%) were known to have IBD, all of whom have levels &gt;600. The most common request indication was diarrhoea (18 patients; 40%), of which twelve had 'ongoing diarrhoea'. Nineteen patients (50%) had some form of endoscopy performed. Table 1 shows the percentage of patients who had endoscopy in the respective faecal calprotectin level groups. A new diagnosis of IBD was made on three patients, all of whom had faecal calprotectin levels &gt;600. Indications for the initial faecal calprotectin tests include 'ongoing diarrhoea', rectal bleeding and 'colitis on imaging'. <h3>Conclusions</h3> 1) The majority of adult inpatient faecal calprotectin requests were inappropriate for age and indication criteria. Based on local guidelines, only two of the twelve patients who had 'ongoing diarrhoea' were older than 50-years-old. Both underwent colonoscopy, where one had no evidence of IBD while the other patient is pending follow-up. There is no association between faecal calprotectin levels and if patients had endoscopy performed. Faecal calprotectin levels &gt;600 gave a 50% pick up rate (3/6 had IBD) but 2/3 would have met the criteria for further colonoscopy regardless of faecal calprotectin level. Inpatient faecal calprotectin test is not a cost–effective way of screening for IBD. Stopping this practice might save the NHS approximately £2000/year at RGH alone and potentially avoid unnecessary endoscopy tests. Discussion between consultant Gastroenterologists and consultant clinical lead in Biochemistry led to a decision to reject all inpatient faecal calprotectin requests not requested by Gastroenterology, Colorectal Surgery or Paediatrics at RGH.

BackgroundThe association of autoimmune liver disease (AILD) and inflammatory bowel disease (IBD) is well documented. IBD affects about 45% of children with autoimmune sclerosing cholangitis (AISC) and about 20% of...

Research Article| December 01 2017 Diagnosis of Inflammatory Bowel Disease AAP Grand Rounds (2017) 38 (6): 64. https://doi.org/10.1542/gr.38-6-64 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Diagnosis of Inflammatory Bowel Disease. AAP Grand Rounds December 2017; 38 (6): 64. https://doi.org/10.1542/gr.38-6-64 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: inflammatory bowel disease, leukocyte l1 antigen complex, irritable bowel syndrome, feces Source: Holtman GA, Lisman-van Leeuwen Y, Day AS, et al. Use of laboratory markers in addition to symptoms for diagnosis of inflammatory bowel disease in children: a meta-analysis of individual patient data. JAMA Pediatr. [published online ahead of print 2017 August 14]; doi: https://doi.org/10.1001/jamapediatrics.2017.1736 An international group of investigators from multiple institutions conducted a meta-analysis augmented with individual patient data (IPD) to assess whether selected blood markers and fecal calprotectin increase the accuracy of diagnosis of inflammatory bowel disease (IBD) in children. The investigators identified published diagnostic studies of pediatric patients (≤18 years old) referred for evaluation for possible IBD that included results of ≥1 laboratory test. The diagnosis of IBD in the included studies was based on histopathologic analysis of endoscopic biopsies or absence of symptoms at clinical follow-up (for a diagnosis of no IBD). The authors of included studies were contacted and asked to provide IPD that included final diagnosis (IBD or no IBD), information about symptoms, and levels from specific laboratory tests (C-reactive protein [CRP] level, erythrocyte sedimentation rate [ESR], platelet count, albumin level, hemoglobin level, and fecal calprotectin level). By using the collected IPD, a logistic regression model that includes presence or absence of the symptoms of abdominal pain, diarrhea, and rectal bleeding was constructed, and the accuracy of these symptoms for diagnosis of IBD was assessed by calculating the area under the receiver operating characteristic curve (AUC). The increased accuracy achieved with the laboratory tests was assessed by measuring the change in AUC in the model after adding the levels for each individual test. In addition, the discriminatory value of each laboratory test alone in pediatric patients with suspected IBD was calculated. Of 16 identified studies, the authors of 8 provided IPD that were used for analysis. These 8 studies included information on 1,120 patients, of whom 560 had IBD; the median prevalence of IBD across the 8 studies was 43% (range, 19%–62%). The AUC of the laboratory markers alone included ESR of 0.84, albumin level of 0.82, CRP level of 0.79, platelet count of 0.79, hemoglobin level of 0.76, and fecal calprotectin level of 0.95. The AUC of the symptoms model was 0.70; adding any of the laboratory markers significantly increased the accuracy of diagnosis. The addition of fecal calprotectin improved the AUC of the symptom model the most out of any marker (ΔAUC, 0.26), followed by ESR (ΔAUC, 0.16). The authors conclude that laboratory markers improve the accuracy of diagnosis of IBD in children with chronic gastrointestinal symptoms. Of the specific laboratory markers assessed, fecal calprotectin increased the diagnostic accuracy the most. Dr Rosenthal has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. Discriminating between children with and those without IBD is often difficult.1 Functional gastrointestinal disorders, such as irritable bowel syndrome, may mimic IBD. Although history and physical examination findings may suggest IBD, endoscopy–an inherently invasive procedure–remains the cornerstone of... You do not currently have access to this content.

Background: Fecal calprotectin (FCP) is a highly sensitive biomarker of intestinal inflammation widely used in diagnostics and monitoring of inflammatory bowel disease (IBD). Immunohistochemical assessment of calprotectin in the bowel mucosa is not a diagnostic standard. Therefore, the aim of this study was to evaluate tissue calprotectin (TCP) as a potential marker providing added insight for pediatric patients with Crohn’s disease (CD). Methods: Fecal and tissue calprotectin were measured in children with CD. The values were correlated with disease activity and histopathological changes of the patients’ endoscopic biopsies. Disease activity was assessed using the Pediatric Crohn’s Disease Activity Index (PCDAI); fecal calprotectin (FCP) was measured with the ELISA test. Immunohistochemical (IHC) staining for calprotectin antigen was performed on the biopsy samples from six bowel segments, and the number of TCP cells was counted per high power field (HPF). Non-parametric statistical tests were used for data analysis. Results: Fifty-seven children with CD with a median age of 10.5 (1–17) years (yrs) were examined for fecal and tissue calprotectin. The patients’ median PCDAI score was 10 (0–63.5), while median FCP was 535 (30–600) μg/g. We observed a correlation between disease activity (PCDAI) and FCP, TCP in inflammatory lesions and in crypts. There was no association either between FCP and TCP or between TCP in epithelium and PCDAI. Conclusion: It seems that IHC detection of calprotectin in bowel mucosa to assess disease behavior may be useful. FCP is a gold-standard biomarker in the diagnosis, monitoring and prognosis of IBD, and its levels correlated well with clinical activity in our study group.