Immunomodulatory assessment of Portulaca oleracea L. extract in a mouse model of colitis.

Ulcerative colitis (UC) is a gastrointestinal inflammatory disease with a multifactorial pathophysiology. This study aims to investigate the immunomodulatory effect of Portulaca oleracea leaf ethanolic extract (POE) on acetic acid (AA)-induced UC in mice. Experimental animals received oral doses of POE (200 mg/kg for 7 days) after an induction of colitis by intrarectal AA administration. In mice with AA-induced UC treated with POE, the results revealed a significant modulation in body weight and colon length. Moreover, treatment with POE downregulated the interleukin 1, 6, and 17, tumor necrosis factor-alpha, gamma interferon, and nuclear factor-kappa B levels compared with the colitis group. Furthermore, POE markedly inhibited histological damage, decreased myeloperoxidase activity and reduced fecal calprotectin level compared with the colitis group. These data are consistent with the reduction in total bacterial content in the colon. Taken together, treatment with POE may reduce colonic inflammation by alleviating the immune response and inhibiting the severity of colitis. The HPLC analysis of POE resulted in the identification of seven medicinal compounds comprising two phenolic acids (ferulic and caffeic acids) and five flavonoids (kaempferol, quercetin, rutin, narenginin and hesperidin). Subsequent analysis of POE by GC-MS revealed ten phytocomponents; the major percentages were hexadecenoic acid, methyl ester (29.8119%), α-linolenic acid (25.8431%), 16-octadecenoic acid, methyl ester (15.1578%) and α-tocopherol (10.7848%). Delta-lactams and alkanes were the minor components. Such natural plant-derived substances and their probable synergistic action appear to contribute to a promising therapeutic protocol for colitis.

Tight control for Crohn's disease with adalimumab-based treatment is cost-effective: an economic assessment of the CALM trial.

OBJECTIVE: To evaluate the cost-effectiveness of an inflammatory biomarker and clinical symptom directed tight control strategy (TC) compared with symptom-based clinical management (CM) in patients with Crohn's disease (CD) naïve to immunosuppressants and biologics using a UK public payer perspective. DESIGN: A regression model estimated weekly CD Activity Index (CDAI)-based transition matrices (remission: CDAI <150, moderate: CDAI ≥150 to <300, severe: CDAI ≥300 to <450, very severe: CDAI ≥450) based on the Effect of Tight Control Management on Crohn's Disease (CALM) trial. A regression predicted hospitalisations. Health utilities and costs were applied to health states. Work productivity was monetised and included in sensitivity analyses. Remission rate, CD-related hospitalisations, adalimumab injections, other direct medical costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. RESULTS: Over 48 weeks, TC was associated with a higher clinical remission (CDAI <150) rate (58.2% vs 46.8%), fewer CD-related hospitalisations (0.124 vs 0.297 events per patient) and more injections of adalimumab (40 mg sc) (mean 31.0 vs 24.7) than CM. TC was associated with 0.032 higher QALYs and £593 higher total medical costs. The ICER was £18 656 per QALY. The ICER was cost-effective in 57.9% of simulations. TC became dominant, meaning less costly but more effective, when work productivity was included. CONCLUSION: A TC strategy as used in the CALM trial is cost-effective compared with CM. Incorporating costs related to work productivity increases the economic value of TC. Cross-national inferences from this analysis should be made with caution given differences in healthcare systems. TRIAL REGISTRATION NUMBER: NCT01235689; Results.

In silico assessment of human Calprotectin subunits (S100A8/A9) in presence of sodium and calcium ions using Molecular Dynamics simulation approach.

Calprotectin is a heterodimeric protein complex which consists of two subunits including S100A8 and S100A9. This protein has a major role in different inflammatory disease and various types of cancers. In current study we aimed to evaluate the structural and thermodynamic changes of the subunits and the complex in presence of sodium and calcium ions using molecular dynamics (MD) simulation. Therefore, the residue interaction network (RIN) was visualized in Cytoscape program. In next step, to measure the binding free energy, the potential of mean force (PMF) method was performed. Finally, the molecular mechanics Poisson-Boltzmann surface area (MMPBSA) method was applied as an effective tool to calculate the molecular model affinities. The MD simulation results of the subunits represented their structural changes in presence of Ca2+. Moreover, the RIN and Hydrogen bond analysis demonstrated that cluster interactions between Calprotectin subunits in presence of Ca2+ were greater in comparison with Na+. Our findings indicated that the binding free energy of the subunits in presence of Ca2+ was significantly greater than Na+. The results revealed that Ca2+ has the ability to induce structural changes in subunits in comparison with Na+ which lead to create stronger interactions between. Hence, studying the physical characteristics of the human proteins could be considered as a powerful tool in theranostics and drug design purposes.

Clinical value of fecal calprotectin.

Inflammatory bowel disease (IBD) denotes a group of chronic incurable disorders characterized by relapsing-remitting inflammation of the gastrointestinal tract. IBD represents a growing global burden with a prevalence exceeding 0.3% in the Western world and an accelerating incidence in newly industrialized countries. The target for treating IBD has shifted in recent years from symptom control to mucosal healing (MH), which has been shown to be associated with favorable long-term outcomes. The gold standard for ascertaining MH is endoscopic assessment, but endoscopy is limited by its invasive nature, high cost, and finite availability. Surrogate biomarkers are therefore of great utility. Calprotectin, a cytosolic protein derived predominantly from neutrophils, is now widely used in this capacity. Calprotectin is found in various bodily fluids at concentrations proportional to the degree of inflammation, including in feces at levels roughly six times higher than in the blood. Fecal calprotectin (FCP) therefore reflects intestinal inflammation. Various assays, including point-of-care and home-based tests, are now available for measuring FCP. FCP is used for screening purposes, to aid in distinguishing inflammatory from non-inflammatory gastrointestinal conditions like irritable bowel syndrome (IBS), as well as in the monitoring of known IBD. The aims of this review are to provide an overview of the methods used to measure FCP and to review the evidence supporting the use of FCP in IBD, particularly as it pertains to screening, monitoring and predicting disease relapse.

Prediction of treatment outcome and relapse in inflammatory bowel disease.

INTRODUCTION: Prediction of treatment outcome and clinical relapse in patients with inflammatory bowel disease (IBD), either ulcerative colitis (UC) or Crohn's disease (CD), is particularly important because therapeutics for IBD are not always effective and patients in remission could frequently relapse. Because undergoing endoscopy for the purpose is sometimes invasive and burdensome to patients, the performance of surrogate biomarkers has been investigated. Areas covered: We particularly featured the performance of patient symptoms, blood markers including C-reactive protein (CRP), fecal markers including fecal calprotectin (Fcal) and fecal immunochemical test (FIT) for prediction of endoscopic mucosal healing (MH) and prediction of relapse. Studies of other modalities and therapeutic drug monitoring (TDM) have also been explored. Expert opinion: Meticulous evaluation of patient symptoms could be predictive for MH in UC. CRP and Fcal may be accurate in prediction of MH of CD when MH is evaluated throughout the entire intestine including the small bowel. Repeated measurements of fecal markers including Fcal and FIT in patients with clinical remission would raise predictability of relapse. Prediction of treatment outcome by monitoring with blood markers including CRP, fecal markers including Fcal, and TDM has frequently been performed in recent clinical trials and shown to be effective.

Calprotectin as an early biomarker of bacterial infections in critically ill patients: an exploratory cohort assessment.

BACKGROUND: Calprotectin is the most abundant protein in the cytosolic fraction of neutrophils, and neutrophil degranulation is a major response to bacterial infections. OBJECTIVES: To assess the value of plasma calprotectin as an early marker of bacterial infections in critically ill patients and compare it with the corresponding values for procalcitonin (PCT), C-reactive protein (CRP) and white blood cell count (WBC). METHODS: We measured daily plasma calprotectin levels in 110 intensive care unit patients using a newly developed turbidimetric assay run on clinical chemistry analysers. The likelihood of infection was determined according to the International Sepsis Forum criteria. RESULTS: Overall, 58 patients (52.7%) developed a suspected or confirmed bacterial infection. Plasma calprotectin predicted such infections within 24 hours with an area under the receiver operating characteristics curve (ROC area) of 0.78 (95% CI, 0.68-0.89). The ROC area for calprotectin was significantly greater than the corresponding ROC areas for WBC (P < 0.001) and PCT (P = 0.02) but only marginally better than the ROC area for CRP (0.71; 95% CI, 0.68-0.89). CONCLUSION: Plasma calprotectin appears to be a useful early marker of bacterial infections in critically ill patients, with better predictive characteristics than WBC and PCT.

Does Helicobacter pylori eradication therapy trigger or protect against Crohn's disease?

Helicobacter pylori (H. pylori) infection is involved in multiple gastrointestinal and extra-gastrointestinal disorders. This review focuses on possible link between H. pylori eradication and Crohn's disease (CD) which is a chronic inflammatory bowel disease (IBD). Fecal calprotectin and; to lesser extent; fecal lactoferrin are sensitive and specific markers for monitoring CD activity. Data about link between H. pylori eradication and CD are limited and inconclusive. The infection likely shifts equilibrium between T helper 1 (Th1) and Th2 immune responses to the Th2 pattern. In subjects genetically predisposed to CD (a Th1-related disease), H. pylori eradication increases Th1 proinflammatory cytokines causing development of CD. In contrast, clarithromycin and/or proton pump inhibitors that are used to eradicate H. pylori can suppress Th1 factors, and theoretically can protect against CD, but there are no data to support this supposition. This Th1/Th2 approach seems very simplistic. Another theory is that alterations in gut microbiota form "continuous antigenic stimulation" predisposing to IBD. H. pylori infection can inhibit such stimulation through activation of regulatory T cells, and thus eradication may predispose to CD. Probiotics weren't found useful in treatment of CD. The reported data about link between H. pylori eradication and CD are currently limited. Case reports, suggesting a positive association between both conditions, provide a very little evidence. On eradicating H. pylori in CD patients and/or patients with high risk for CD, patient counseling and follow-up in addition to measuring fecal calprotectin may help monitor CD activity. (Acta gastro-enterol. belg., 2016, 79, 349-354).

Cost-effectiveness of Crohn's disease post-operative care.

AIM: To define the cost-effectiveness of strategies, including endoscopy and immunosuppression, to prevent endoscopic recurrence of Crohn's disease following intestinal resection. METHODS: In the "POCER" study patients undergoing intestinal resection were treated with post-operative drug therapy. Two thirds were randomized to active care (6 mo colonoscopy and drug intensification for endoscopic recurrence) and one third to drug therapy without early endoscopy. Colonoscopy at 18 mo and faecal calprotectin (FC) measurement were used to assess disease recurrence. Administrative data, chart review and patient questionnaires were collected prospectively over 18 mo. RESULTS: Sixty patients (active care n = 43, standard care n = 17) were included from one health service. Median total health care cost was $6440 per patient. Active care cost $4824 more than standard care over 18 mo. Medication accounted for 78% of total cost, of which 90% was for adalimumab. Median health care cost was higher for those with endoscopic recurrence compared to those in remission [$26347 (IQR 25045-27485) vs $2729 (IQR 1182-5215), P < 0.001]. FC to select patients for colonoscopy could reduce cost by $1010 per patient over 18 mo. Active care was associated with 18% decreased endoscopic recurrence, costing $861 for each recurrence prevented. CONCLUSION: Post-operative management strategies are associated with high cost, primarily medication related. Calprotectin use reduces costs. The long term cost-benefit of these strategies remains to be evaluated.

The Modified Mayo Endoscopic Score (MMES): A New Index for the Assessment of Extension and Severity of Endoscopic Activity in Ulcerative Colitis Patients.

BACKGROUND AND AIMS: Current endoscopic activity scores for ulcerative colitis (UC) do not take into account the extent of mucosal inflammation. We have developed a simple endoscopic index for UC that takes into account the severity and distribution of mucosal inflammation. METHODS: In this multicentre trial, UC patients undergoing colonoscopy were prospectively enrolled. For the Modified Score (MS), the sum of Mayo Endoscopic Subscores (MESs) for five colon segments (ascending, transverse, descending, sigmoid and rectum) was calculated. The Extended Modified Score (EMS) was obtained by multiplying the MS by the maximal extent of inflammation. The Modified Mayo Endoscopic Score (MMES) was obtained by dividing the EMS by the number of segments with active inflammation. Colon biopsies were obtained from the rectum and sigmoid, as well as from all inflamed segments, by standard methods. Clinical activity was scored according to the Partial Mayo Score (PMS). Biological activity was scored according to C-reactive protein (CRP) and faecal calprotectin (FC) levels. Histological activity was scored according to the Geboes Score (GS). RESULTS: One hundred and seventy-one UC patients (38% female, median age 47 years, median disease duration 13 years) were included. The MMES correlated significantly with the PMS (r = 0.535), CRP (r = 0.238), FC (r = 0.730) and GS (r = 0.615) (all p < 0.001). Median MMES scores were significantly higher in patients with clinical, biological or histological activity (all p ≤ 0.001) CONCLUSIONS: The MMES is an easy to use endoscopic index for UC that combines the severity analysis of the MES with disease extent, and correlates very well with clinical, biological and histological disease activity.

Fecal calprotectin in diagnosis and clinical assessment of inflammatory bowel disease.

The fecal neutrophil-derived biomarker calprotectin has several features of an ideal noninvasive test for detecting intestinal inflammation: it is simple, reliable, and low in cost. Its utility in differentiating inflammatory bowel diseases (IBDs) from functional conditions such as irritable bowel syndrome is well documented. Fecal calprotectin (FC) correlates closely with endoscopic activity of IBD. Emerging evidence suggest its usefulness in serial monitoring of disease activity and of therapy success in IBD. A low FC concentration predicts persistence of clinical remission especially in non-symptomatic ulcerative colitis and Crohn's colitis. Here, an overview is given to the current role of FC in diagnosis and clinical assessment of IBD.

The role of fecal calprotectin in assessment of hepatic encephalopathy in patients with liver cirrhosis.

INTRODUCTION: Calprotectin is a cytoplasmatic protein of neutrophilic granulocytes and it is an established marker for the assessment of localized intestinal inflammation. AIM: To explore correlation between values of fecal calprotectin and degree of liver cirrhosis and hepatic encephalopathy. METHODS: We included 60 patients with liver cirrhosis and 37 healthy patients as controls. Patients revealing other causes of abnormal calprotectin results (gastrointestinal bleeding or inflammatory bowel disease) were excluded. The degree of liver insufficiency was assessed according to the Child-Pugh classification and Model of End Stage Liver Disease (MELD), and degree of hepatic enceph- alopathy by West-Haven criteria, serum concentration of ammonium ion and the number connection test. RESULTS: The mean value of fecal calprotectin in patients with liver cirrhosis was 189.1 ± 168.0 µg/g, and 35.0 ± 26.0 µg/g in the control group, respectively. We have confirmed significantly higher fecal calprotectin in patients with cirrhosis (p < 0.001). There were no significant differences in values of fecal calprotectin between the patients with different stages of liver cirrhosis according to Child-Pugh classification and MELD score (p > 0.05). We observed statistically significant difference comparing fecal calprotectin by West-Haven criteria of hepatic encephalopathy (p < 0.001), while there were no correlation with the number connection test and serum concentration of ammonium ion (p > 0.05). CONCLUSION: We confirmed significantly higher values of fecal calprotectin in patients with liver cirrhosis, especially in hepatic encephalopathy according to West-Haven criteria.

Rapid fecal calprotectin level assessment and the SIBDQ score can accurately detect active mucosal inflammation in IBD patients in clinical remission: a prospective study.

BACKGROUND AND AIMS: Mucosal healing is an important predictor of disease-related outcome in patients with inflammatory bowel disease (IBD) patients, including those in clinical remission. However, colonoscopy is an invasive procedure and many patients decline repeated endoscopic examinations. We aimed to assess whether noninvasive biomarkers could accurately detect endoscopic mucosal inflammatory activity in IBD patients in clinical remission. METHODS: We conducted a prospective observational cohort study on IBD patients in clinical remission at Colentina Hospital, Bucharest. Clinical activity was assessed using the Mayo score and Crohn's Disease Activity Index (CDAI), quality of life was assessed using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Serum C-reactive protein (CRP) and fecal calprotectin (FC) levels were determined. All patients underwent ileo-colonoscopy to assess mucosal inflammatory activity. RESULTS: 48 patients were included in this study, with 67% showing endoscopic disease activity. SIBD questionnaire and FC performed well as noninvasive markers of intestinal inflammation (AUROC 0.78 and 0.77, respectively), while CRP could not accurately predict endoscopic disease activity. Fecal calprotectin levels > 30 µg/g showed a 93% sensitivity and a 50% specificity for detecting inflammatory changes of the mucosa while a combined test using FC > 30µg/g and a SIBDQ score < 6 achieved 81.2% sensitivity and 75% specificity, respectively, in detecting active endoscopic disease. CONCLUSION: Fecal calprotectin and SIBDQ have good diagnostic accuracy in detecting mucosal inflammatory changes in IBD patients in clinical remission. Combining simple, noninvasive tests such as the SIBDQ and FC levels appears to be a practical method for monitoring disease activity in these patients, possibly reducing the need for repeat endoscopic examinations.

The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease: a systematic review and meta-analysis.

OBJECTIVES: Fecal calprotectin (FC) is increasingly used during the diagnosis of inflammatory bowel disease (IBD), outperforming blood markers during investigation in children. Tests that reduce endoscopy rates in children with suspected gut inflammation would be beneficial. We aimed to determine the usefulness of FC in children undergoing their primary investigation for suspected IBD by systematic review and meta-analysis. METHODS: An electronic search was performed with keywords relating to IBD and calprotectin in multiple electronic resources from 1946 to May 2012; a hand search was also performed. Inclusion criteria were studies that reported FC levels before the endoscopic investigation of IBD in patients less than 18 years old. Studies were evaluated using the Quality Assessment of Diagnostic Accuracy Studies tool, and a meta-analysis was performed using a hierarchical summary receiver operating curve model. RESULTS: Eight papers met the inclusion criteria (six prospective and two retrospective case-control studies); methodological quality was determined in detail for each study. The 8 studies presented FC levels at presentation in 715 patients, 394 pediatric IBD patients, and 321 non-IBD controls. Pooled sensitivity and specificity for the diagnostic utility of FC during the investigation of suspected pediatric IBD were 0.978 (95% confidence interval (CI), 0.947-0.996) and 0.682 (95% CI, 0.502-0.863), respectively; the positive and negative likelihood ratios were 3.07 and 0.03, respectively. CONCLUSIONS: FC has a high sensitivity and a modest specificity during the diagnosis of suspected pediatric IBD. Further work is required to determine the effect of FC levels on endoscopy rates and its role during the re-evaluation of those with confirmed disease.

Effectiveness and cost-effectiveness of measuring fecal calprotectin in diagnosis of inflammatory bowel disease in adults and children.

BACKGROUND & AIMS: The level of fecal calprotectin (FC) can predict the onset of inflammatory bowel disease (IBD) with high accuracy and precision. We evaluated the cost-effectiveness of using measurements of FC to identify adults and children who require endoscopic confirmation of IBD. METHODS: We constructed a decision analytic tree to compare the cost-effectiveness of measuring FC before endoscopy examination with that of direct endoscopic evaluation alone. A second decision analytic tree was constructed to evaluate the cost-effectiveness of FC cutoff levels of 100 µg/g vs 50 µg/g (typically used to screen for intestinal inflammation). The primary outcome measure was the incremental cost required to avoid 1 false-negative result by using FC level to diagnose new-onset IBD. RESULTS: In adults, FC screening saved $417/patient but delayed diagnosis for 2.2/32 patients with IBD among 100 screened patients. In children, FC screening saved $300/patient but delayed diagnosis for 4.8/61 patients with IBD among 100 screened patients. If endoscopic biopsy analysis remained the standard for diagnosis, direct endoscopic evaluation would cost an additional $18,955 in adults and $6250 in children to avoid 1 false-negative result from FC screening. Sensitivity analyses showed that cost-effectiveness of FC screening varied with the sensitivity of the test and the pre-test probability of IBD in adults and children. Pre-test probabilities for IBD of ≤75% in adults and ≤65% in children made FC screening cost-effective, but it was cost-ineffective if the probabilities were ≥85% and ≥78% in adults and children, respectively. Compared with the FC cutoff level of 100 µg/g, the cutoff level of 50 µg/g cost an additional $55 and $43 for adults and children, respectively, but it yielded 2.4 and 6.1 additional accurate diagnoses of IBD per 100 screened adults and children, respectively. CONCLUSIONS: Screening adults and children to measure fecal levels of calprotectin is effective and cost-effective in identifying those with IBD on a per-case basis when the pre-test probability is ≤75% for adults and ≤65% for children. The utility of the test is greater for adults than children. Increasing the FC cutoff level to ≥50 µg/g increases diagnostic accuracy without substantially increasing total cost.

E-health empowers patients with ulcerative colitis: a randomised controlled trial of the web-guided 'Constant-care' approach.

BACKGROUND: The natural history of ulcerative colitis requires continuous monitoring of medical treatment via frequent outpatient visits. The European health authorities' focus on e-health is increasing. Lack of easy access to inflammatory bowel disease (IBD) clinics, patients' education and understanding of the importance of early treatment at relapse is leading to poor compliance. To overcome these limitations a randomised control trial 'Constant-care' was undertaken in Denmark and Ireland. METHODS: 333 patients with mild/moderate ulcerative colitis and 5-aminosalicylate acid treatment were randomised to either a web-group receiving disease specific education and self-treatment via http://www.constant-care.dk or a control group continuing the usual care for 12 months. A historical control group was included to test the comparability with the control group. We investigated: feasibility of the approach, its influence on patients' compliance, knowledge, quality of life (QoL), disease outcomes, safety and health care costs. RESULTS: 88% of the web patients preferred using the new approach. Adherence to 4 weeks of acute treatment was increased by 31% in Denmark and 44% in Ireland compared to the control groups. In Denmark IBD knowledge and QoL were significantly improved in web patients. Median relapse duration was 18 days (95% CI 10 to 21) in the web versus 77 days (95% CI 46 to 108) in the control group. The number of acute and routine visits to the outpatient clinic was lower in the web than in the control group, resulting in a saving of 189 euro/patient/year. No difference in the relapse frequency, hospitalisation, surgery or adverse events was observed. The historical control group was comparable with the control group. CONCLUSION: The new web-guided approach on http://www.constant-care.dk is feasible, safe and cost effective. It empowers patients with ulcerative colitis without increasing their morbidity and depression. It has yet to be shown whether this strategy can change the natural disease course of ulcerative colitis in the long term.

Development and assessment of a modified Pediatric Crohn Disease Activity Index.

The Pediatric Crohn Disease Activity Index (PCDAI) is an established and validated measure of disease activity in children with Crohn disease. However, its use in the research setting can be limited because of ambiguity of the subjective and anthropometric components of the index. Here we propose and evaluate a modified PCDAI (Mod PCDAI) consisting of the laboratory measures of the PCDAI plus C-reactive protein. This Mod PCDAI can provide an indication of disease activity because it correlates with the PCDAI, physicians' global assessment, and fecal calprotectin, and therefore may provide a suitable alternative to the PCDAI when required.

Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN-elastase, CRP, and clinical indices.

OBJECTIVES: The aim of this study was to compare the performance of fecal lactoferrin (Lf), calprotectin (Cal), polymorphonuclear neutrophil elastase (PMN-e), as well as serum C-reactive protein (CRP) in patients with inflammatory bowel diseases (IBD) to address (a) whether these markers can differentiate IBD patients with endoscopically assessed inflammation from IBD patients without inflammation and from irritable bowel syndrome (IBS); (b) whether they correlate with endoscopic severity of inflammation; and (c) whether a combination of fecal markers with the respective disease-specific activity indices may increase the diagnostic accuracy with reference to the endoscopic severity of inflammation. METHODS: Fecal levels of Lf, Cal, and PMN-e and serum CRP were assessed in 139 patients undergoing diagnostic ileocolonoscopy (54 IBS patients, 42 ulcerative colitis [UC], 43 Crohn's disease [CD]). Disease activity was determined for CU with the colitis activity index (CAI) and for CD with the Crohn's disease activity index (CDAI). The performance of each marker with reference to endoscopic inflammatory activity was assessed by computing correlations, and sensitivity and specificity using published as well as adjusted cutoffs. A comprehensive activity index was computed by combining results from fecal markers, serum CRP, and a clinical activity index. RESULTS: UC or CD patients with active inflammation demonstrated significantly higher levels of Lf, Cal, and PMN-e in feces as well as serum-CRP when compared to patients with inactive inflammation as well as patients with IBS (all P < 0.05). Using adjusted cutoffs enabled a marked improvement of all markers with an overall diagnostic accuracy in IBD of 80.0% for Lf, 80.0% for Cal, 74.1% for PMN-e, 64.0% for CRP, and 79.0% for the respective clinical disease scores. Cal showed the highest diagnostic accuracy in CD (81.4%), whereas Lf was superior to the other markers in UC (83.3%). The comprehensive activity index yielded a further improvement of sensitivity and specificity, with a diagnostic accuracy of 95.3% for UC patients. CONCLUSION: The fecal markers Lf, Cal, and PMN-e are able to differentiate active IBD from inactive IBD as well as from IBS. None of these three stool markers is consistently superior in its ability to reflect endoscopic inflammation, but all three are superior to CRP in their diagnostic accuracy. A combination of the stool markers with the CRP and a disease-specific activity index in a categorical comprehensive activity index can increase the diagnostic accuracy with reference to the endoscopic inflammation in UC.