Effect of mucosal healing (Mayo 0) on clinical relapse in patients with ulcerative colitis in clinical remission

Objective: The aim of this study was to identify the effect of mucosal healing (MH) on clinical relapse in patients with ulcerative colitis (UC) who are in clinical remission, with special reference to Mayo endoscopic subscore 0.

Methods: Between November 2005 and December 2013, medical records from a total of 215 patients with UC who underwent colonoscopic examination at the time of clinical remission were retrospectively reviewed. Endoscopic MH was defined as a ‘0 point’ of Mayo endoscopic subscore (Mayo 0). Patients were categorized into two groups according to Mayo endoscopic subscore and then analyzed.

Results: The baseline characteristics of both groups (MH vs. no-MH), including age at diagnosis, gender, and initial clinical and colonoscopic findings, were not significantly different. The median follow-up duration was 80 (12–118) months. Factors predictive of longer clinical remission duration were age ≥30 years at diagnosis (≥30 years vs. <30 years; hazard ratio [HR] 3.16, 95% CI 1.88–5.30, p?p?=?0.015), and presence of MH at clinical remission (HR 1.95, 95% CI 1.15–3.32, p?=?0.014). With a Cox regression model, patients with MH at clinical remission were more likely to have longer duration of clinical remission than patients without MH.

Conclusion: The achievement of MH, Mayo 0 in particular, in patients with UC who are in clinical remission is important in predicting a favorable disease course prognosis.     

Fecal calprotectin is a strong predictive marker of relapse in Chinese patients with Crohn’s disease: a two-year prospective study

Objective: To evaluate the predictive value of fecal calprotectin (FC) for clinical relapse in Chinese patients with quiescent Crohn’s disease (CD) and to further investigate the correlation between FC and intestinal inflammation.

Methods: Sixty-two patients with a diagnosis of quiescent CD were consecutively enrolled in this prospective study. Fecal samples were collected and enteroscopy were performed to detect mucosal lesions at the beginning of the study. Patients were followed until the first relapse or by the end of the two-year follow-up. The calprotectin concentration was measured using a quantitative enzyme-linked immunoassay.

Results: Of the 62?CD patients, 29 had a relapse (median time of relapse: 8.44 months). The median follow-up months was 8.16 (4.98–13.59). The cut off level of 225?μg/g provided the maximal area under the receiver operating characteristic curve (AUC) of .775 for detecting the relapse of CD patients. Meanwhile, fecal occult blood had an added value. The multivariate Cox regression model showed that FC was the strongest predictor of the risk of relapse (risk ratio (RR): 6.315; p?=?.001). FC correlated most closely with the simple endoscopic score for Crohn’s disease (SES-CD) (r?=?0.524, p?<?.001).

Conclusions: FC correlated significantly with gut inflammation and could be a reliable predictor of relapse in Chinese patients with CD.     

Fecal calprotectin as a noninvasive test to predict deep remission in patients with ulcerative colitis

Mucosal healing (MH) has become a major target in the management of ulcerative colitis (UC). Because repeat endoscopy is expensive and invasive, we aimed to evaluate fecal calprotectin (FC) as an alternative marker to predict MH in UC.Eighty patients with UC in clinical remission were consecutively included in a prospective observational study. FC was measured using a quantitative enzyme-linked immunosorbent assay. The colonic mucosa was assessed for endoscopic and histological measures of inflammatory status. Endoscopic and histological remission were defined according to the Mayo endoscopic subscore (MES) and Geboes score (GS), respectively. Deep remission was defined as a combination of the MES and GS. FC performance and cutoff values for identifying MH and deep remission were determined using contingency tables and receiver operator characteristic (ROC) and area under the curve (AUC) analysis.The median FC concentration in patients who met the criteria for deep remission (MES ≤1 and GS < 3.1) was 65.5 μg/g, while that in patients with disease activity was 389.6 μg/g (P = .025). A FC cutoff value of 100 μg/g, determined by the ROC analysis, resulted in sensitivity and specificity of 91.7% and 57.1%, respectively, for histological remission, and 82.4% and 60.9%, respectively, for deep mucosal remission. Positive correlations were detected between FC concentrations with the histologic (CC: 0.435; P < .001) and the combined endoscopic and histologic (CC: 0.413; P < .001) scores.FC can be used confidently as a noninvasive biomarker to predict deep remission in patients with UC in clinical remission when concentrations are below 100 μg/g.     

Diagnosing colorectal cancer and inflammatory bowel disease in primary care: The usefulness of tests for faecal haemoglobin,faecal calprotectin,anaemia and iron deficiency. A prospective study

Objective: Abdominal complaints are common reasons to consult primary care but they are seldom caused by colorectal cancer (CRC), high-risk adenomas (HRAs), or inflammatory bowel disease (IBD). Reliable diagnostic aids would be helpful in deciding which patients to refer for bowel imaging. Our aim was to assess the value of a faecal immunochemical test (FIT) and a faecal calprotectin (FC) test in detecting CRC, HRAs and IBD in primary care, and the value of combining these tests with anaemia and iron-deficiency tests.

Materials and methods: This prospective study included 373 consecutive patients that received a FIT or a FC test ordered by a primary care physician. We collected samples for FITs, FC tests, full blood counts and iron-deficiency tests. Physicians were instructed to refer patients with a positive FIT or FC test (cut-off ≥100μg/g) for bowel imaging. The patients’ presenting symptoms were recorded. Patients were followed for 2 years.

Results: The best test for detecting CRC and IBD was the combination of the FIT and haemoglobin concentration. This test had a sensitivity, specificity, positive predictive value and negative predictive value of 100%, 61.7%, 11.7% and 100%, respectively. The FIT detected a significantly larger proportion of CRC, HRAs and IBD than the FC test (0.92 versus 0.46, 95% confidence interval 0.22–0.67).

Conclusion: A negative FIT combined with a normal haemoglobin concentration could rule out CRC and IBD with a high degree of safety. This could be useful in prioritising referrals for bowel imaging from primary care.     

Fecal calprotectin is an effective diagnostic tool that differentiates inflammatory from functional intestinal disorders

Abstract

Background. The clinical pictures of functional gastrointestinal disorders and inflammatory diseases can be quite similar leading to inappropriate and expensive investigations. Objective. To investigate fecal calprotectin (FC) diagnostic performance in different gastrointestinal conditions. Material and methods. Stool specimens of 66 outpatients referred for colonoscopy were collected for further FC determination. Diagnostic accuracy was assessed by the area under the curve (AUC). Sensitivity (Se), specificity (Sp), positive (PPV), and negative predictive values (NPV) were calculated according to the presence of inflammation and the main final diagnosis. Results. Histological inflammation was found in 45 (68%) patients: 24 had a diagnosis of inflammatory bowel disease (IBD) while 21 reported miscellaneous conditions (5 microscopic colitis, 2 eosinophilic colitis, and 14 nonspecific chronic colitis). The diagnosis in the 21 (32%) patients without inflammation was irritable bowel syndrome (IBS). Median FC values were 268 µg/g (95% CI, 151–343) and 49 µg/g (95% CI, 23–101) in patients with and without inflammation, respectively (p = 0.0001). AUC value of FC was 0.811 (Se = 68.9%, Sp = 71.4%, PPV = 83.8%, and NPV = 56.3% with a cutoff value of 100 µg/g) for discriminating between patients with and without inflammation and 0.931 (Se = 87.5%, Sp = 90.5%, PPV = 91.3%, and NPV = 86.4% with a cutoff value of 150 µg/g) for discriminating between patients with IBS and IBD. Using the cutoff value recommended by the manufacturer (50 µg/g), we found Se =100%, Sp =52.4%, PPV =70.6%, and NPV =100% for the diagnosis of IBD. Conclusions. FC appears to be a reliable noninvasive biomarker of intestinal inflammation useful to improve the appropriateness of colonoscopy requests.     

Association between Fecal Calprotectin and Mucosal Healing in Pediatric Patients with Crohn’s Disease Who Have Achieved Sustained Clinical Remission with Anti-Tumor Necrosis Factor Agents

Background/AimsAlthough mucosal healing (MH) is acknowledged as the treatment target in the treat-to-target era, there are limitations on repeated endoscopic examinations, especially in pediatric patients. We aimed to investigate whether fecal calprotectin (FC) could serve as a surrogate marker for the assessment of MH in pediatric patients with Crohn’s disease (CD) who have achieved sustained clinical remission (CR) while treated with anti-tumor necrosis factor (TNF) agents.MethodsThis multicenter retrospective cross-sectional study included pediatric CD patients who had sustained a CR for at least 6 months with anti-TNF agents and who simultaneously underwent ileocolonoscopy and FC tests during follow-up. MH was defined as the absence of any ulcer on ileocolonoscopy.ResultsA total of 131 patients were included in this study. MH was observed in 87 patients (66.7%). The FC level was significantly lower in patients with MH than in those without MH (median 49.0 mg/kg vs 599.0 mg/kg; p<0.001). According to the multivariate logistic regression analysis, FC was the only factor associated with MH (odds ratio, 0.62; 95% confidence interval [CI], 0.52 to 0.73; p<0.001). According to the receiver operating characteristic curve analysis, the optimal cutoff value for FC for the association with MH was <140 mg/kg (area under the curve 0.890, 95% CI 0.829 to 0.951, sensitivity 78.2%, specificity 88.6%, p<0.001).ConclusionsFC was associated with MH in pediatric patients with CD who had achieved a sustained CR for at least 6 months with anti-TNF agents. In these patients, FC can be used to stratify patients and guide decisions regarding ileocolonoscopy in the treat-to-target era.     

Diagnostic accuracy of a quantitative faecal immunochemical test vs. symptoms suspected for colorectal cancer in patients referred for colonoscopy

Abstract

Objective: Determine diagnostic accuracy of a quantitative faecal immunochemical haemoglobin test (QuikRead go^® FIT, Orion Diagnostica Oy) in symptomatic patients referred for colonoscopy, at various cut-offs and for one or two tests.

Methods: Patients referred to four endoscopy units in mid-Sweden between 2013 and 2017 provided information on lower abdominal symptoms and faecal samples from two separate days prior to colonoscopy.

Results: In all, 5.4% (13/242) patients had colorectal cancer (CRC). For one FIT at cut-off 10?µg Hb/g faeces, sensitivity for CRC was 92% (95% CI 78–100%) and specificity 77% (95% CI 72–83%); equal to 74%; 95% CI 68–80 (178/242) colonoscopies potentially avoidable and one CRC missed. Based on the maximal outcome of two FITs, sensitivity was 100%, specificity 71% (66–77%) and 68%; 95% CI 62–74 (160/237) colonoscopies potentially avoidable. Among 17% (42/242) patients with one FIT of >200?µg Hb/g faeces, 85% (11/13) had CRC. Positive predictive values of FIT varied 16.9–26.2% depending on cut-off and one or two FITs, whereas NPVs were 99% and above in all scenarios.

In 60 patients reporting rectal bleeding, one FIT at cut-off 10?µg Hb/g discriminated well between CRC and other conditions (p?=?.001). In regression models, FIT was more important than age, sex and all symptoms.

Conclusion: One or two FITs in symptomatic patients referred for colonoscopy imply powerful risk stratification abilities for CRC, even among patients reporting rectal bleeding. Larger studies in various settings will clarify how to make the best use of this opportunity.

Trial registration: Clinicaltrails.gov NCT 02491593     

Disparities in Colorectal Cancer Screening Practices in a Midwest Urban Safety-Net Healthcare System

Aims

Although colorectal cancer screening (CRC) using stool-based test is well-studied, evidence on fecal immunochemical test (FIT) patterns in a safety-net healthcare system utilizing opportunistic screening is limited. We studied the FIT completion rates and adenoma detection rate (ADR) of positive FIT-colonoscopy (FIT-C) in an urban safety-net system.

Methods

We performed a retrospective cross-sectional chart review on individuals?≥?50 years who underwent CRC screening using FIT or screening colonoscopy, 09/01/2017–08/30/2018. Demographic differences in FIT completion were studied; ADR of FIT-C was compared to that of screening colonoscopy.

Results

Among 13,427 individuals with FIT ordered, 7248 (54%) completed the stool test and 230 (48%) followed up a positive FIT with colonoscopy. Increasing age (OR 1.01, CI 1.01–1.02), non-Hispanic Blacks (OR 0.87, CI 0.80–0.95, p?=?0.002), current smokers (OR 0.84, CI 0.77–0.92, p?<?0.0001), those with Medicaid (OR 0.86, CI 0.77–0.96, p?=?0.006), commercial insurance (OR 0.85, CI 0.78–0.94, p?=?0.002), CCI score?≥?3 (OR 0.82, CI 0.74–0.91, p?<?0.0001), orders by family medicine providers (OR 0.87, CI 0.81–0.94, p?<?0.0001) were associated with lower completion of stool test. Individuals from low median household income cities had lower follow-up of positive FIT, OR 0.43, CI 0.21–0.86, p?=?0.017. ADR of FIT-C was higher than that of screening colonoscopy.

Conclusion

Adherence to CRC screening is low in safety-net systems employing opportunistic screening. Understanding demographic differences may allow providers to formulate targeted strategies in high-risk vulnerable groups.

     

Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results,mucosal healing,and risk of relapse

AIM: To assess the risk of relapse in ulcerative colitis(UC) patients in clinical remission using mucosal status and fecal immunochemical test(FIT) results. METHODS: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores(MESs) and FIT results.RESULTS: Patients with an MES of 0(n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3(n = 100, 52%)(HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result(fecal hemoglobin concentrations ≤ 100 ng/m L) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score(HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse(HR = 0.11, 95%CI: 0.04-0.23).CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing(MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.     

Serial semi-quantitative measurement of fecal calprotectin in patients with ulcerative colitis in remission

Background: Fecal calprotectin (FC) correlates with clinical and endoscopic activity in ulcerative colitis (UC), and it is a good predictor of relapse. However, its use in clinical practice is constrained by the need for the patient to deliver stool samples, and for their handling and processing in the laboratory. The availability of hand held devices might spread the use of FC in clinical practice.

Objectives: To evaluate the usefulness of a rapid semi-quantitative test of FC in predicting relapse in patients with UC in remission.

Materials and methods: Prospective, multicenter study that included UC patients in clinical remission for ≥6 months on maintenance treatment with mesalamine. Patients were evaluated clinically and semi-quantitative FC was measured using a monoclonal immunochromatography rapid test at baseline and every three months until relapse or 12 months of follow-up.

Results: One hundred and ninety-one patients had at least one determination of FC. At the end of follow-up, 33 patients (17%) experienced clinical relapse. Endoscopic activity at baseline (p?=?.043) and having had at least one FC?>?60?μg/g during the study period (p?=?.03) were associated with a higher risk of relapse during follow-up. We obtained a total of 636 semi-quantitative FC determinations matched with a three-month follow-up clinical assessment. Having undetectable FC was inversely associated with early relapse (within three months), with a negative predictive value of 98.6% and a sensitivity of 93.9%.

Conclusions: Serial, rapid semi-quantitative measurement of FC may be a useful, easy and cheap monitoring tool for patients with UC in remission.     

Indigo naturalis is effective even in treatment-refractory patients with ulcerative colitis: a post hoc analysis from the INDIGO study

Background

We recently reported the efficacy of indigo naturalis (IN) in patients with active ulcerative colitis (UC) in a randomized controlled trial (INDIGO study). However, few studies have been conducted to investigate whether IN is effective even in treatment-refractory cases, such as in those with steroid dependency and anti-TNF refractoriness.

Methods

In the INDIGO study, 86 patients with active UC were randomly assigned to an IN group (0.5–2.0 g daily) or placebo group. The rate of clinical response (CR), mucosal healing (MH), and change in fecal calprotectin (FCP) levels was compared between refractory [patients with steroid-dependent disease, previous use of anti-TNF-α, and concomitant use of immunomodulators (IM)] and non-refractory patients. We also analyzed factors predicting CR and MH at week 8.

Results

The rates of CR of IN group were significantly higher than placebo group, even in patients with steroid-dependent disease (p < 0.001), previous use of anti-TNF-α (p = 0.002), and concomitant use of IM (p = 0.013). The rates of MH in IN group were significantly higher than in placebo group in patients with steroid-dependent disease (p = 0.009). In the IN group, median FCP levels, at week 8, were significantly lower than baseline in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α (p < 0.001, respectively). Multivariate analysis indicated that the previous use of anti-TNF-α was not a predictive factor for CR and MH at week 8.

Conclusions

In a sub-analysis of data from a randomized placebo-controlled trial, we found that IN may be useful even in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α.

     

Diagnostic accuracy of one or two faecal haemoglobin and calprotectin measurements in patients with suspected colorectal cancer

Background: The role of faecal biomarkers in patients at ‘high risk’ of colorectal cancer (CRC) is not yet defined. Pre-analytical factors, such as heterogeneity of biomarker distribution within faeces, may influence their optimisation in clinical practice. We undertook to determine whether repeat or combined biomarker testing improves diagnostic accuracy for CRC or clinically significant disease.

Methods: Patients referred with suspected CRC provided two separate faecal samples each for faecal immunochemical testing (FIT) and faecal calprotectin (FC) prior to investigation. Diagnostic accuracy of FIT and FC were evaluated based on final diagnoses.

Results: Five hundred fifteen patients completed a full colorectal evaluation. The optimal cut-off for CRC using a single FIT was ≥12 µgHb/g faeces (84.6% sensitivity, 88.5% specificity). For two FIT, the cut-off was ≥43 µgHb/g faeces if either and ≥2 µgHb/g faeces if both were positive. There was no advantage in their diagnostic accuracy compared with a single FIT. FC had a lower diagnostic accuracy for CRC than FIT, which was not improved by repeat FC. No benefit was identified with FIT-FC combined.

For CRC, significant adenomatous polyps and organic enteric disease combined, FIT and FC performed similarly to each other but were poorer predictors (AUC 0.677 and 0.660). There was no uplift in diagnostic accuracy when the tests were repeated or combined.

Conclusion: This study supports using a single FIT at a cut-off close to that recommended by NICE DG30 to improve diagnostic accuracy for ‘two-week wait’ patients referred with suspected CRC.     

Serum 1,3-beta-D-glucan as a noninvasive test to predict histologic activity in patients with inflammatory bowel disease

BACKGROUND 1,3-beta-D-glucan(BG)is a ubiquitous cell wall component of gut microorganisms.We hypothesized that the serum levels of BG could reflect active intestinal inflammation in patients with inflammatory bowel disease.AIM To determine whether the serum BG concentrations correlate with intestinal inflammation.METHODS A prospective observational study was performed in a tertiary referral center,from 2016 to 2019,in which serum BG was determined in 115 patients with Crohn’s disease(CD),51 with ulcerative colitis(UC),and 82 controls using a photometric detection kit.Inflammatory activity was determined by ileocolonoscopy,histopathology,magnetic resonance enterography,and biomarkers,including fecal calprotectin(FC),C-reactive protein,and a panel of cytokines.The ability of BG to detect active vs inactive disease was assessed using the area under the receiver operating characteristic curve.In subgroup analysis,serial BG was used to assess the response to therapeutic interventions.RESULTS The serum BG levels were higher in CD patients than in controls(P=0.0001).The BG levels paralleled the endoscopic activity in CD patients and histologic activity and combined endoscopic and histologic activity in both CD and UC patients.The area under the curve(AUC)in receiver operating characteristic analysis to predict endoscopic activity was 0.694[95%confidence interval(CI):0.60-0.79;P=0.001]in CD,and 0.662(95%CI:0.51-0.81;P=0.066)in UC patients.The AUC in receiver operating characteristic analysis to predict histologic activity was 0.860(95%CI:0.77-0.95;P<0.001)in CD,and 0.786(95%CI:0.57-0.99;P=0.015)in UC patients.The cut-off values of BG for both endoscopic and histologic activity were 60μg/mL in CD,and 40μg/mL in UC patients.Performance analysis showed that the results based on BG of 40 and 60μg/mL were more specific for predicting endoscopic activity(71.8%and 87.2%for CD;and 87.5%and 87.5%for UC,respectively)than FC(53.3%and 66.7%for CD;and 20%and 80%for UC,respectively);and also histologic activity(60.5%and 76.3%for CD;and 90.0%and 95.0%for UC,respectively)than FC(41.7%and 50.0%for CD;and 25%and 50%for UC,respectively).Regarding the clinical,endoscopic,and histologic activities,the BG levels were reduced following therapeutic intervention in patients with CD(P<0.0001)and UC(P=0.003).Compared with endoscopic(AUC:0.693;P=0.002)and histologic(AUC:0.868;P<0.001)activity,no significant correlation was found between serum BG and transmural healing based on magnetic resonance enterography(AUC:0.576;P=0.192).Positive correlations were detected between BG and IL-17 in the CD(r:0.737;P=0.001)and the UC group(r:0.574;P=0.005),and between BG and interferon-gamma in the CD group(r:0.597;P=0.015).CONCLUSION Serum BG may represent an important novel noninvasive approach for detecting mucosal inflammation and therapeutically monitoring inflammatory bowel diseases,particularly in CD.     

The diagnostic role and clinical association of serum proteinase 3 anti-neutrophil cytoplasmic antibodies in Chinese patients with inflammatory bowel disease

Abstract

Background and aim: Accurate differentiation of patients with ulcerative colitis (UC) or Crohn’s disease (CD) is important for appropriate therapy and prognosis. This study was designed to explore the utility of proteinase 3 anti-neutrophil cytoplasmic antibodies (PR3-ANCA) in the diagnosis of Chinese patients with inflammatory bowel disease (IBD).

Methods: Blood samples were collected from 216 Chinese patients, including 175 IBD and 41 colorectal polyps (disease control). Clinical characteristics were extracted from electronic medical records.

Results: Serum PR3-ANCA were increased in UC patients compared to those with CD or colorectal polyps (p?<?.0001). PR3-ANCA was negative in colorectal polyps and there was no significant difference between CD and colorectal polyps (p?>?.05). Using the cut-off value of 20 chemiluminescent units (CU) provided by manufacturer, the positive rate of PR3-ANCA was higher in UC than CD (41.7% vs. 1.1%; p?<?.0001). Receiver operating characteristic (ROC) analysis demonstrated an area under the curve (AUC) of 0.89 (95% CI: 0.84–0.95; p?<?.0001) for differentiating UC from CD and suggested an optimized cutoff of 7.3 CU which improved sensitivity from 41.7% to 57.1%, while maintaining a specificity of 98.9%. PR3-ANCA in severe UC patients were higher than those with moderate UC (p?<?.05), no difference was found between those in remission or with mild or moderate activity (p?>?.05).

Conclusions: Serum PR3-ANCA is a potentially useful clinical biomarker in Chinese patients with IBD. A modified cut-off value of 7.3 CU improves the performance for distinguishing UC from CD.     

Assessment of disease activity by fecal immunochemical test in ulcerative colitis

AIM To evaluate the efficacy of quantitative fecal immunochemical test(FIT) as biomarker of disease activity in ulcerative colitis(UC).METHODS Between February 2013 and November 2014, a total of 82 FIT results, obtained in conjunction with colonoscopies, were retrospectivelyevaluated for 63 patients with UC. The efficacy of FIT for evaluation of disease activity was compared to colonoscopic findings. Quantitative fecal blood with automated equipment examined from collected feces. Endoscopic disease severity were assessed using the Mayo endoscopic subscore(MES) classification. The extent of disease were classified by proctitis(E1), left sided colitis(E2), and extensive colitis(E3). Clinical activity were subgrouped by remission or active.RESULTS All of 21 patients with MES 0 had negative FIT( 7 ng/mL), but 22 patients with MES 2 or 3 had a mean FIT of 134.89 ng/m L. The sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV) and accuracy of negative FIT about mucosal healing were 73.33%, 81.82%, 91.49%, 51.43% and 73.17%, respectively. The sensitivity, specificity, PPV, NPV and accuracy of predictive value of positive FIT(cutoff value 100 ng/mL) about active disease status were 45.45%, 93.33%, 71.43%, 82.35%and 26.83%, respectively. Among patients with clinical remission, FIT was negative in 31(81.6%) of 38 cases, with a mean fecal hemoglobin concentration of 6.12 ng/mL(range, negative to 80.9 ng/mL) for this group of patients. Among patients with clinical active disease, FIT was negative in 16(36.4%) out of 44 cases, with a mean fecal hemoglobin concentration 167.4 ng/mL for this group of patients. FIT was positively correlated with endoscopic activity(r = 0.626, P 0.01) and clinical activity(r = 0.496, P 0.01). But, FIT did not correlate with the extent of disease(r =-0.047, P = 0.676)CONCLUSION Quantitative FIT can be a non-invasive and effective biomarker for evaluation of clinical and endoscopic activity in UC, but not predict the extent of disease.     

TWEAK is not elevated in patients with newly diagnosed inflammatory bowel disease

Objective: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) may be involved in the pathogenesis of inflammatory bowel disease. The aim was to investigate if TWEAK may reflect disease activity in inflammatory bowel disease.

Materials and methods: In this cohort study, 139 consecutive patients with newly diagnosed and previously untreated inflammatory bowel disease – 95 with ulcerative colitis (UC) and 44 with Crohn’s disease (CD) – underwent colonoscopy. Disease activity was assessed by the Mayo score and the Mayo endoscopic score (MES) for UC, or the Simple Endoscopic Score (SES) for CD. Serum C-reactive protein (CRP) and fecal calprotectin were measured in IBD patients, as were plasma TWEAK levels in patients and 85 healthy subjects. Associations between TWEAK levels and disease activity markers were explored.

Results: In the total IBD group, the median (interquartile range) TWEAK level was 430?pg/ml (109–6570), in UC 502?pg/ml (109–4547) and in CD patients 352?pg/ml (101–9179), respectively. Healthy subjects had a median (IQR) TWEAK of 307?pg/ml (63–3492). There were no significant differences in TWEAK levels between the total IBD group and healthy control subjects, nor between UC and CD, or between UC/CD and healthy subjects. Furthermore, we found no significant associations between Mayo scores, MES-UC, SES-CD, CRP, and fecal calprotectin with plasma TWEAK levels.

Conclusions: Plasma TWEAK levels do not reflect disease activity or the grade of inflammation in patients with newly diagnosed inflammatory bowel disease. NCT01551563.     

Elevated fecal levels of eosinophil granule proteins predict collagenous colitis in patients referred to colonoscopy due to chronic non-bloody diarrhea

Objective: Colonoscopy with biopsy sampling is often performed to detect collagenous colitis (CC) and lymphocytic colitis (LC) in patients with chronic non-bloody diarrhea. However, the diagnostic yield is low and incurs high costs. Fecal calprotectin (FC) and myeloperoxidase (MPO) indicate intestinal inflammation in ulcerative colitis (UC) and Crohn’s disease (CD). In CC, elevated fecal levels of eosinophil protein X (EPX) and eosinophil cationic protein (ECP) have been reported. We aimed to evaluate if F-EPX, F-ECP, FC, and F-MPO could predict the diagnostic outcome in patients with chronic non-bloody diarrhea referred to colonoscopy. We also evaluated serum (S) EPX and ECP in this regard.

Methods: Of 67 included patients, 63 (94%) underwent colonoscopy with biopsy sampling. Fecal EPX, F-ECP, FC, F-MPO, S-EPX, and S-ECP were analyzed.

Results: Diagnostic outcome: normal: n?=?46 (73%), CC: n?=?9 (14%), LC: n?=?4 (6%), UC: n?=?2 (3%), CD: n?=?2 (3%). Higher levels of F-EPX and F-ECP were found in CC compared to a normal diagnostic outcome (p?=?0.01). No change was noted in any of the fecal markers in LC. When all of the fecal markers were normal the probability of a normal diagnostic outcome was 92%. We found no differences in S-EPX and S-ECP between the groups.

Conclusion: Elevated F-EPX and F-ECP could predict CC. None of the fecal markers predicted LC. Serum-EPX and S-ECP are not useful for the diagnosis of CC, LC, UC, or CD. With normal levels in all of the analyzed fecal markers, there is a low probability of a pathologic diagnostic outcome.     

Role of faecal calprotectin as a predictor of endoscopic activity in paediatric patients with ulcerative colitis

IntroductionColonoscopy 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 methodsSingle-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.ResultsA 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) (1000 μg/g, IQR 575–1800 μg/g vs. 100 μg/g, IQR 80–223 μg/g, p < 0.001). At a cut-off of 298.5 μg/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.DiscussionFC is an accurate surrogate marker of endoscopic activity in children with clinically quiescent UC.     

The correlation between fecal calprotectin,simple clinical colitis activity index and biochemical markers in ulcerative colitis during high-dose steroid treatment

Abstract

Objective. Monitoring active ulcerative colitis (UC) is essential for making correct and timely treatment decisions. The current monitoring is based on symptom scores and biochemical markers, among which the role of fecal calprotectin (FC) is debated. The aims were to assess the development in FC during steroid treatment and to compare FC with symptom scores and biochemical markers. Material and methods. A prospective observational study, including 16 patients with active UC requiring high-dose steroid treatment. FC, C-reactive protein (CRP), leukocytes, hemoglobin, albumin, and simple clinical colitis activity index (SCCAI) were assessed before the initiation of treatment, as well as on days 2, 6, 13, and 27. The one-year follow-up data were retrospectively obtained. Results. All patients had significant decreasing levels of FC (–1014 mg/kg, p = 0.0061), CRP (–10 mmol/l, p = 0.0313), and SCCAI (–3, p = 0.0002) during the first 4 days. After 27 days, the FC had decreased to 216 mg/kg (p = 0.002). A significant correlation between the changes in CRP and SCCAI was found (r_s = 0.65, p = 0.03) but not between FC and CRP or SCCAI. Overall, significant correlations between absolute levels of FC, CRP, and SCCAI were found. Levels of FC on day 0 and day 4 were not predictive of sustained clinical remission at 1-year follow up. Conclusions. FC, CRP, and SCCAI seem to be reliable markers of treatment response during steroid treatment. High initial levels of FC and a subsequent rapid reduction during steroid treatment were identified. FC levels were not found to be predictive of disease prognosis after one year.