Calprotectin Test Research Articles

N24 At Home Calprotectin a United Kingdom Patient Perspectives and Tertiary Center Experience

Abstract Background Home faecal calprotectin tests (HFCT) have been available for some years with slow uptake to use in the UK. During the Sars-Cov-2 pandemic use increased as it allowed a measure of disease activity when lab testing in some areas ceased. In a United Kingdom tertiary referral IBD unit, CalproSmart was introduced in 2020. We analysed completion rates of HFCT and the barriers and enablers patients experienced in its use. Methods Data from the CalproSmart portal was analysed. Total patients registered was compared against the number that had completed a test. Age, sex and return rates per annum as well as local or out of area patients were included. All patients who enrolled to receive a HFCT were sent an anonymous online questionnaire using MS Forms. Descriptive statistics were used to analysis the results with a thematic analysis of free form text answers. Results A total of N=304 patients were enrolled on the CalproSmart portal over a three-year period from October 2020 until July 2021. HFCT was completed by 118 (39%) of these patients. Completion was highest in 2020 78% of patients who enrolled on the system completed a HFCT. There was a slight trend towards females being more likely to complete at 23% versus 16% of males. There was no sign of age as a determinant to completion. Of the 118 patients who completed the HFCT 84 (71%) were out of local area patients and 34 (29%) local patients. There were 54 (17%) questionnaires returned. All but 4 (7%) respondents had attempted or completed the HFCT. When asked why they wanted to try a HFCT 39 (72%) patients indicated not having to go to hospital/GP as their primary reason with getting an instant result 29 (54%) and seeing your own result 27 (50%) coming in next. 13 (24%) cited more disease control as a reason to try the test. People found the test mostly easy to use but when comparing overall happiness with the HFCT kits 9 people reported they were somewhat unhappy or unhappy. People were either happy or unhappy with the HFC test usability is a theme that is generated as a barrier and a facilitator for some (see figure 1). When asked which they would prefer to do in future CalproSmart at home or bring your sample to either your GP or hospital n=45 (83%) preferred HFCT. Figure 1 Q 12 Overall how happy were you with CalproSmart home calprotectin kit? Free text answer comparison Conclusion During the pandemic HFCT were popular and out of area patients were more likely to complete the kits. Despite the low return rates those that chose to complete HFCT were in most of cases happy to continue HFCT. With, attention to patient selection and enhanced training on the HFCT there is a case for the continued use in services that have altered significantly since the pandemic.

P511 Evaluation of home faecal calprotectin testing to aid remote management and enhanced self-management of Inflammatory Bowel Disease.

Abstract Background Faecal calprotectin (FC) is an established biomarker for patients with irritable bowel disease (IBD). A treat to target strategy has been shown to be successful in managing these patients and the development of a home FC test (IBDoc) opens the door to a more patient centred approach for IBD management. Methods IBD patients in the IBD database at Basildon and Thurrock University Hospital with a compatible smart phone who had previously agreed to monitor FC at home using IBDoc were eligible for inclusion. Usability, patient experience, engagement and understanding of the IBDoc, along with satisfaction with enhanced remote and self-management, were assessed using a mixed methods approach via an online questionnaire consisting of Likert scale questions and a limited number of free text questions. Results 47 participants were enrolled in the study. Over 85% of responses showed patients found the IBDoc to be user friendly. Over 80% of responses indicated patients were happy with their understanding of the result and what it meant for their disease status. Thematic analysis revealed a personalised care plan for each patient is of crucial importance. Clinicodemographic variables found to influence patient satisfaction with use of the IBDoc and enhanced remote and self-management were treatment type, education history and disease type. Conclusion Results demonstrate excellent acceptance of the IBDoc system with good scores for usability and patient understanding. This shows that the home test can be used as an objective patient reported outcome within a treat to target approach. Better educational materials and clinically guided personalised care plans, along with the IBDoc home FC test, make IBD a viable candidate for self-management at the same level as traditionally self-managed diseases such as diabetes.

A Point-of-Care Faecal Test Combining Four Biomarkers Allows Avoidance of Normal Colonoscopies and Prioritizes Symptomatic Patients with a High Risk of Colorectal Cancer.

Most colonoscopies performed to evaluate gastrointestinal symptoms detect only non-relevant pathologies. We aimed to evaluate the diagnostic accuracy of a qualitative point-of-care (POC) test combining four biomarkers (haemoglobin, transferrin, calprotectin, and lactoferrin), a quantitative faecal immunochemical test (FIT) for haemoglobin, and a quantitative faecal calprotectin (FC) test in symptomatic patients prospectively recruited. Colorectal cancer (CRC), adenoma requiring surveillance, inflammatory bowel disease (IBD), microscopic colitis, and angiodysplasia were considered significant pathologies. A total of 571 patients were included. Significant pathology was diagnosed in 118 (20.7%), including 30 CRC cases (5.3%). The POC test yielded the highest negative predictive values: 94.8% for a significant pathology and 100% for CRC or IBD if the four markers turned negative (36.8% of the patients). Negative predictive values of FIT, FC, and its combination for diagnosis of a significant pathology were 88.4%, 87.6%, and 90.8%, respectively. Moreover, the positive predictive value using the POC test was 82.3% for significant pathology when all biomarkers tested positive (6% of the patients), with 70.6% of these patients diagnosed with CRC or IBD. The AUC of the POC test was 0.801 (95%CI 0.754-0.848) for the diagnosis of a significant pathology. Therefore, this POC faecal test allows the avoidance of unnecessary colonoscopies and prioritizes high risk symptomatic patients.

Barriers in inflammatory bowel disease care in Central and Eastern Europe: a region-specific analysis.

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic immune-mediated diseases with a high incidence and prevalence in Europe. Since these are diseases with associated disability, they require complex management and the availability of high-quality healthcare resources. We focused on the analysis of IBD care in selected countries of Central and Eastern Europe (Croatia, the Czech Republic, Hungary, Moldova, Poland, Romania and Slovakia) targeting the availability and reimbursement of diagnostic and therapeutic modalities, the role of IBD centers and also education and research in IBD. As part of the analysis, we created a questionnaire of 73 statements organized in three topics: (1) diagnostics, follow-up and screening, (2) medications and (3) IBD centers. The questionnaire was filled out by co-authoring IBD experts from individual countries, and then the answers and comments on the questionnaire were analyzed. We identified that despite the financial burden, which still partially persists in the region, the availability of some of the cost-saving tools (calprotectin test, therapeutic drug monitoring) differs among countries, mainly due to variable reimbursement from country to country. In most participating countries, there also remains a lack of dedicated dietary and psychological counseling, which is often replaced by recommendations offered by gastroenterologists. However, there is adequate availability of most of the currently recommended diagnostic methods and therapies in each participating country, as well as the implementation of established IBD centers in the region.

Fecal immunochemical test for hemoglobin versus fecal calprotectin to monitor endoscopic activity in inflammatory bowel disease.

endoscopy identifies inflammatory activity, however, it is an unpleasant test and is not always accessible. The aim of the study was to compare the usefulness of quantitative fecal immunochemical test (FIT) versus fecal calprotectin (FC) to determine endoscopic activity in patients with inflammatory bowel disease (IBD). cross-sectional prospective observational study. The stool samples were collected within three days before starting the preparation for the colonoscopy. We used the Mayo index for ulcerative colitis (UC) and the simplified endoscopic index for Crohn's disease (CD). Mucosal healing (MH) was defined as the score 0 points in each of the endoscopic indices. eighty-four patients were included, 40 (47.6 %) with UC. In patients with IBD, FIT and FC showed a significant correlation with the presence of inflammatory activity/MH on endoscopy, with no statistically significant differences between the two receiver-operating characteristic (ROC) curves. Both tests improved their diagnostic performance when assessing patients with UC; the Spearman correlations between FIT and FC and endoscopic inflammatory activity were r = 0.6 (p = 0.0001) and r = 0.7 (p = 0.0001), respectively. In Crohn's disease, the diagnostic utility of both tests was lower. FIT is an alternative to monitor endoscopic activity among ulcerative colitis patients. In Crohn's disease, more studies are needed to determine the role of fecal biomarkers.

The usefulness of fecal hemoglobin and calprotectin tests in diagnosing significant bowel diseases: a prospective study

Objectives Although colonoscopy remains the gold standard for determining bowel diseases, it’s invasive and expensive. New non-invasive diagnostic methods are urgently needed as an initial screening modality. We aimed to investigate the value of fecal calprotectin (FC) and fecal immunochemical test (FIT) in differentiation of significant and non- significant bowel diseases. Methods In this prospective study, consecutive individuals were included if they underwent colonoscopy for symptoms of lower gastrointestinal (GI) tract, positive fecal occult blood test, surveillance for IBD or colorectal cancer (CRC) screening. Diagnostic value of FC and FIT in discriminating significant bowel diseases (advanced neoplasia, active inflammatory bowel diseases or bowel inflammation due to other causes) and non-significant bowel diseases (normal, asymptomatic diverticulum, non-adenomatous polyp, or non-advanced neoplasia) were evaluated. Results Among 201 individuals included, 107 patients had significant bowel diseases. FC and FIT had an area under the curve (AUC) of 0.722 (95% confidence interval [CI] 0.653–0.792) and 0.797 (95%CI 0.734–0.860), respectively, for determining significant bowel diseases. Combination of FC and FIT predicted significant bowel diseases with an AUC, sensitivity, specificity, and accuracy of 0.832 (95% CI 0.775–0.890), 77.6%, 74.5%, and 76.1%, respectively. Moreover, combination of FC and FIT was more sensitive among patients with lower GI symptoms than asymptomatic individuals (80.8% vs. 74.1%) to identify significant bowel diseases. Conclusions A single measurement of FC or FIT is not sufficiently accurate to identify patients with significant bowel disease. However, combination of FC and FIT can help increase the sensitivity, especially in patients with lower GI symptoms.

Disease Monitoring of the Ileoanal Pouch: How to Utilize Biomarkers, Imaging, and Pouchoscopy.

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. 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.

S936 Factors Associated With Fecal Calprotectin Sample Collection Compliance: An IBD Center Quality Improvement Project

Introduction: Regular assessment of objective markers of inflammatory bowel disease (IBD) activity is recommended. Fecal calprotectin (Fcal) is a non-invasive and inexpensive biomarker of disease activity, however, patient compliance with this test is variable and incompletely described. We assessed compliance rates with Fcal tests and identified factors associated with non-compliance. Methods: As a quality improvement project, we conducted a retrospective chart review of IBD patients who had a Fcal test ordered by us between August 2021 and December 2021. Demographic, clinical, disease-related, and test-related (location of lab relative to the patient’s visit in clinic or at home) information were recorded to determine predictors for non-compliance. Simple statistical analysis and multivariable logistic regression was performed. Results: Of 303 patients, 165 (54.4%) had an order for Fcal. Of the Fcal tests ordered, 55 (33.3%) were not completed. Between those with complete versus incomplete tests, IBD remission status (67.8% vs. 83.7%, p = 0.033), history of prior Fcal order completion (93.2% vs. 68.4%, p = 0.001), and test ordered to an external site (62.7% vs. 85.5%, p = 0.004) were significantly different. A multivariable logistic regression with these factors as well as age, gender, telehealth vs. in-person consultation, and patient residence revealed that history of a prior completed Fcal test is independently associated with subsequent test completion (odds ratio (OR) = 8.3, 95% CI 1.9-35.5, p = 0.004). Fcal testing location (institutional or third-party) was marginally significant (OR = 0.27, 95% CI 0.7-1.0, p = 0.051). A multivariable linear regression for days between test order and completion found that tests ordered for external locations are associated with delayed completion (95% CI 5.2-20.6, p = 0.002). Conclusion: In this single center analysis with Fcal testing in patients with IBD, we found that a history of incomplete testing is associated with subsequent non-compliance, and distant location of the lab is associated with delayed completion of the test. These findings suggest that ordering providers should identify additional methods to educate on the importance of disease monitoring with Fcal and when possible, simplify the lab used for testing. Future availability of at home Fcal tests may be helpful in this regard. Table 1. - Linear Regressions for Predictors of Fecal Calprotectin Compliance Logistic Regression for Test Compliance Regression for Delayed Testing Completion Estimate Effect Size (B) Standard Error P - Value 95% Confidence Interval Estimate Effect Size (B) Standard Error P - Value 95% Confidence Interval Age 0.017 0.015 0.248 0.998-1.048 0.148 0.104 0.163 -31.309-7.575 Gender -0.441 0.543 0.417 0.222-1.866 0.877 3.635 0.810 0.062-0.357 IBD Remission -0.949 0.624 0.128 0.114-1.316 -0.331 3.895 0.933 -6.421-8.176 Consultation Type -.0523 0.528 0.322 0.210-1.570 0.102 3.992 0.980 -8.151-7.490 History of Fecal Calprotectin Completion 2.116 0.741 0.004 1.942-35.493 6.628 2.625 0.357 -7.699-20.956 Fecal Calprotectin Testing Location -1.304 0.668 0.51 0.073-1.005 12.875 3.843 0.002 5.160-20.591

Diagnostic approach to chronic bowel diseases in children

Diagnosing inflammatory bowel diseases in children and differentiating them from functional disorders is complicated based on clinical assessment, laboratory data, and radiological, endoscopic, and histological signs. Therefore, in paediatrics, substantial attention has been given to standard invasive evaluation methods. Recently, research efforts have been directed towards using faecal calprotectin as a sensitive non-invasive stool test.
 The aim of the research was to study the diagnostic value of faecal calprotectin in pediatric chronic inflammatory bowel diseases. The paper discusses faecal calprotectin's diagnostic and monitoring role in 35 children aged 3 to 17 years with ulcerative colitis, non-specific non-ulcerative colitis, and irritable bowel syndrome. The concentration of the faecal calprotectin level was examined by ELISA using monoclonal antibodies.
 Results. The study shows that in patients with non-specific ulcerative and non-ulcerative colitis, the faecal calprotectin level exceeds the normal ranges 2-5 times, corresponding to clinical and morphological manifestations of the diseases and the level of inflammatory markers. However, this biological marker does not exceed the average values in children with irritable bowel syndrome.
 Conclusions. The faecal calprotectin test allows us to differentiate organic and functional intestinal diseases, monitor chronic inflammatory bowel disease activity dynamics, and estimate treatment effectiveness. Applying the faecal calprotectin test within the framework of primary medical care can decrease the number of referrals for invasive endoscopic, laboratory, and radiologic examinations in pediatric patients with inflammatory bowel diseases

Effect of disease duration on fecal biomarkers in ulcerative colitis: a prospective cohort study

BackgroundBiomarkers such as fecal calprotectin (FC) and fecal immunochemical occult blood tests (FIT) for ulcerative colitis (UC) are used in clinical practice. In this study, the effect of UC disease duration on FC was investigated and compared to that on FIT.MethodsOne hundred twenty-eight colonoscopic examinations and two fecal biomarkers measurements were performed. The cases of UC were divided into short- and long-term disease-duration groups or categorized into three groups with disease durations of 0–5, 6–13, and 14–38 years. We analyzed correlations between biomarker levels and endoscopic scores, including the Mayo endoscopic subscore (MES), ulcerative colitis endoscopic index of severity, and the sum of MES.ResultsIn the analysis of short- and long-term disease durations, the three endoscopic scores and biomarker levels showed significant correlations in both long-term and short-term groups. Most of the correlation coefficients for the individual long-term group were lower than the corresponding values for all cases, while most of the correlation coefficients for the individual short-term groups were higher than the corresponding values for all cases. In the three-group analysis (disease durations of 0–5, 6–13, and 14–38 years), the two biomarkers and three endoscopic scores showed significant correlations, and most of the correlation coefficients between biomarkers and endoscopic scores tended to be lower in the long-term follow-up group. In the receiver operating characteristic analysis for predicting mucosal healing in the three groups, the area under the curve for FC and FIT concentrations in the 0–5 year disease-duration group showed particularly higher values than those for the other two groups.ConclusionsSimilar to FIT, FC is affected by the duration of UC, indicating that FC may be a highly useful biomarker, especially in short-term disease.

Association between body mass index and fecal calprotectin levels in children and adolescents with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common pediatric functional gastrointestinal disorder. It is characterized by recurrent abdominal pain and changes in bowel habits and is more prevalent in obese patients. We investigated the association between obesity and IBS in pediatric patients through fecal calprotectin testing.Patients under 18 years of age with IBS who underwent fecal calprotectin testing from January 2015 through April 2020 were retrospectively investigated. The patients were divided into groups based on body mass index (BMI): group I (BMI < 85th percentile) and group II (BMI ≥ 85th percentile). Group II was divided into group IIa, overweight (85th percentile ≤ BMI < 95th percentile), and group IIb, obese (BMI ≥ 95th percentile).Among 277 included patients, 202 (72.9%) were in group I, and 75 (27.1%) were in group II (mean calprotectin levels, 75.60 ± 103.48 vs 45.89 ± 66.57 µg/g, respectively; P = .006). There were significant differences in mean calprotectin levels between groups I and IIa (75.60 ± 103.48 vs 45.45 ± 63.38 µg/g, respectively; P = .028) and groups I and IIb (75.60 ± 103.48 vs 46.22 ± 69.59 µg/g, respectively; P = .025). There was a significant difference in mean calprotectin levels between groups I and II (85.69 ± 142.13 vs 32.04 ± 28.17 µg/g, respectively; P = .029) among patients between 6 and 12 years of age but not among adolescents aged between 12 and 18 years (P = .139). Fecal calprotectin was lower when moderate-to-severe fatty livers were observed by ultrasound compared with normal livers (68.52 ± 97.22 vs 18.53 ± 18.56 µg/g, respectively; P = .017).Fecal calprotectin levels were higher in normal-weight pediatric IBS patients than in their obese counterparts, and this difference was more prominent in younger patients. In young children, IBS symptoms are thought to be influenced more by factors other than intestinal inflammation.

Impact of Preanalytical Factors on Calprotectin Concentration in Stool: A Multiassay Comparison.

Measuring calprotectin concentration in stool is increasingly important in monitoring disease activity and treatment response in inflammatory bowel disease. This study evaluates the impact of preanalytical storage conditions on reliability of calprotectin testing using 5 different calprotectin immunoassays. Aliquots of homogenized fresh fecal samples in untreated or extracted form were stored at room temperature or 4°C. Calprotectin concentration was measured day 0 to 4 and 8. Five different immunoassays and accompanying extraction buffers were used (CALiaGold, Phadia EliA, Bühlmann fCal turbo, ELISA Bühlmann, Inova Quanta Flash). Repeated measurements of change from baseline calprotectin levels over time were analyzed using a mixed model analysis. Calprotectin concentrations declined over time under all preanalytical conditions with all assays, except for extracted feces stored at 4°C. The rate of decline was greatest in untreated stool kept at room temperature, reaching significant difference from baseline already after 1 day (P &lt; 0.001). In extracted feces kept at room temperature, significant difference from baseline was reached after 2 days, and in untreated feces at 4°C, after 4 days. However, the results differed significantly between assays. After 4 days of storage at room temperature, the mean calprotectin decline from baseline differed between 30% and 60%, dependent on the assay used. Fecal calprotectin concentration in stool samples declines over time, and the rate of decline is greater at higher temperatures. In extracted feces stored at 4°C, calprotectin is most stable. It is assay-dependent how long extracted feces stored at 4°C give reliable test results.

Comparing outcomes from tailored meta-analysis with outcomes from a setting specific test accuracy study using routine data of faecal calprotectin testing for inflammatory bowel disease

BackgroundMeta-analyses of test accuracy studies may provide estimates that are highly improbable in clinical practice. Tailored meta-analysis produces plausible estimates for the accuracy of a test within a specific setting by tailoring the selection of included studies compatible with a specific setting using information from the target setting. The aim of this study was to validate the tailored meta-analysis approach by comparing outcomes from tailored meta-analysis with outcomes from a setting specific test accuracy study.MethodsA retrospective cohort study of primary care electronic health records provided setting-specific data on the test positive rate and disease prevalence. This was used to tailor the study selection from a review of faecal calprotectin testing for inflammatory bowel disease for meta-analysis using the binomial method and the Mahalanobis distance method. Tailored estimates were compared to estimates from a study of test accuracy in primary care using the same routine dataset.ResultsTailoring resulted in the inclusion of 3/14 (binomial method) and 9/14 (Mahalanobis distance method) studies in meta-analysis. Sensitivity and specificity from tailored meta-analysis using the binomial method were 0.87 (95% CI 0.77 to 0.94) and 0.65 (95% CI 0.60 to 0.69) and 0.98 (95% CI 0.83 to 0.999) and 0.68 (95% CI 0.65 to 0.71), respectively using the Mahalanobis distance method. The corresponding estimates for the conventional meta-analysis were 0.94 (95% CI 0.90 to 0.97) and 0.67 (95% CI 0.57 to 0.76) and for the FC test accuracy study of primary care data 0.93 (95%CI 0.89 to 0.96) and 0.61 (95% CI 0.6 to 0.63) to detect IBD at a threshold of 50 μg/g. Although the binomial method produced a plausible estimate, the tailored estimates of sensitivity and specificity were not closer to the primary study estimates than the estimates from conventional meta-analysis including all 14 studies.ConclusionsTailored meta-analysis does not always produce estimates of sensitivity and specificity that lie closer to the estimates derived from a primary study in the setting in question. Potentially, tailored meta-analysis may be improved using a constrained model approach and this requires further investigation.

Calprotectin Lateral Flow Test: Consistent Across Criteria for Ruling Out Periprosthetic Joint Infection.

There are multiple sets of criteria used to define periprosthetic joint infection. The objective of this study is to compare the diagnostic accuracy of the calprotectin lateral flow point-of-care (POC) test in total knee arthroplasty (TKA) patients to diagnose infection using 3 different sets of criteria: (1) 2013 Musculoskeletal Infection Society, (2) 2018 Intentional Consensus Meeting (ICM), and (3) the 2019 proposed European Bone and Joint Infection Society criteria as reference standards. From October 2018 to January 2020, 123 intraoperative synovial fluid samples were prospectively collected from revision total knee arthroplasty patients and tested using a calprotectin lateral flow POC assay. Data were reviewed and adjudicated by 2 independent reviewers blinded to calprotectin test results. The 3 criteria sets had 91.8% agreement. Using 2013 Musculoskeletal Infection Society criteria, the POC test demonstrated a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of 98.1%, 95.7%, 94.5%, 98.5%, and 0.969, respectively. Using the 2018 ICM, the POC test demonstrated a sensitivity, specificity, PPV, NPV, and AUC of 98.2%, 98.5%, 98.2%, 98.5%, and 0.984, respectively. Using the 2019 proposed European Bone and Joint Infection Society criteria, the POC test demonstrated a sensitivity, specificity, PPV, NPV, and AUC of 93.2%, 100.0%, 100.0%, 94.2%, and 0.966, respectively. The calprotectin lateral flow POC test had excellent sensitivity and specificity across current available periprosthetic joint infection definitions, with the best performance observed when applying 2018 ICM criteria. Diagnostic I.

Diagnostic performance of calprotectin and APPY-1 test in pediatric acute appendicitis: a systematic review and a meta-analysis.

Pediatric acute appendicitis (AA) is a challenging pathology to diagnose. In the last decades, multiple biomarkers have been evaluated in different human biological samples to improve diagnostic performance. This study aimed to examine the diagnostic performance of serum, fecal and urinary calprotectin as well as the role of the APPY-1 biomarker panel in pediatric acute appendicitis. We conducted a systematic review of the literature that involved an extensive search in the main databases of medical bibliography (Medline, PubMed, Web of Science and SciELO). Two independent reviewers selected the relevant articles based on the previously defined inclusion and exclusion criteria. Methodological quality of the selected article was rated using the QUADAS2 index. Data extraction was performed by two independent reviewers. A synthesis of the results, a standardization of the metrics and two random-effect meta-analyses, one for serum calprotectin and one for APPY-1, were performed. The research resulted in 173 articles. Thirty-eight duplicates were removed. Among the remaining 135 articles, we excluded 125 following the inclusion and exclusion criteria, resulting in the 10 studies included in this review. This systematic review included data from of 3901 participants (1276 patients with confirmed diagnosis of AA and 2625 controls). The age of the participants ranged from 0 to 21years. Four of the studies compared serum calprotectin values and reported significant differences between groups, but inconsistent results regarding cutoff points, sensitivity and specificity. Two publications compared urinary values of calprotectin and presented inconsistent results regarding sensitivity and specificity as well. One publication evaluated the diagnostic performance of fecal calprotectin, but it did not provide data on measured values. Four studies evaluated the diagnostic performance of APPY-1 test in pediatric acute appendicitis. The calculated pooled sensitivity and specificity of those studies were 97.37 (95% CI 95.60-98.44) and 36.74 (95% CI 32.28-41.44), respectively, and the calculated pooled NLR, 0.0714 (95% CI 0.041-0.115). Serum calprotectin has limited diagnostic yield in pediatric acute appendicitis. Its performance seems to increase with the hours of clinical evolution and in advanced AA, although the evidence is limited. There is not enough evidence on the usefulness of urinary or fecal calprotectin in the diagnosis of pediatric acute appendicitis. On the other hand, the APPY-1 is a reliable test to exclude the diagnosis of AA in patients at low or moderate risk according to PAS and Alvarado Score.

Synovial Biomarkers to Detect Chronic Periprosthetic Joint Infection: A Pilot Study to Compare Calprotectin Rapid Test, Calprotectin ELISA Immunoassay and Leukocyte Esterase Test.

Periprosthetic joint infection (PJI) is a devastating complication after joint replacement surgery, and making diagnosis is often far from obvious. Calprotectin was recently proposed as a promising synovial biomarker to detect PJI. To our knowledge, no comparative study exists between enzyme-linked immunosorbent assay (ELISA) and rapid calprotectin test (CalFAST). Our purpose was to compare these methods with leukocyte esterase (LE) test from synovial fluid of painful knee arthroplasty subjected to infectious workup. Ninety-three patients were included in this prospective observational study. They underwent synovial fluid aspiration that was analyzed for cell count, microbiological culture, LE test, calprotectin rapid test, and calprotectin immunoassay dosage. The 2018 Consensus Statements criteria for PJI were used to diagnose PJI. Sensitivity, specificity, positive and negative likelihood ratio, and receiver operating characteristic were calculated for detection methods and compared. We categorized 39 patients as infected and 50 patients as not infected. The sensitivity comparing the ELISA test and CalFAST test was similar, 92.3% and 97.4%, respectively. LE rapid test showed 46% of sensitivity and 94% of specificity. The highest specificity was found with ELISA test (100%). Comparing the receiver operating characteristic curves by z-test, there were statistically significant differences between LE strip test and the other two methods. Otherwise, no statistically significant differences were present between ELISA and CalFAST test. Synovial calprotectin detection has high accuracy in knee PJI diagnosis, both ELISA and rapid test. LE strip test remains a good test to confirm the diagnosis of PJI in case of positivity. In clinical practice, the calprotectin rapid test can be considered an excellent point-of-care test.

Specific Immunoglobulin E and G to Common Food Antigens and Increased Serum Zonulin in IBS Patients: A Single-Center Bulgarian Study.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder whose pathogenesis is considered multifactorial, including abnormal gut motility, visceral hyperreactivity, psychological factors, disturbances in the brain-gut axis, leaky gut, oxidative stress, etc. We aimed to investigate serum levels of specific immunoglobulin E and G to common food antigens and zonulin and to assess their use in clinical practice for patients with IBS. Material and methods. We included 23 participants, 15 with IBS (diagnosed according to the Rome IV criteria) and 8 healthy controls. We investigated serum levels of specific IgG antibodies to 24 food antigens, specific IgE antibodies to 20 food antigens, anti-celiac antibodies, fecal calprotectin and serum zonulin by ELISA. Results. Food-specific positive IgG antibodies were significantly higher in patients with IBS than in controls (p = 0.007). IgE-mediated allergic reactions were found in five patients with IBS; no one had anti-TG antibodies. One-third of IBS patients demonstrated a low degree of chronic inflammation (positive fecal calprotectin test > 50 ng/mL) without specific bacterial infection. Serum levels of zonulin in IBS patients were higher than in healthy controls (0.378 ± 0.13 vs. 0.250 ± 0.14 ng/mL, p = 0.0315). However, no correlations between clinical symptoms and zonulin levels were found. Conclusion. The mechanisms of IgG hypersensitivity and low degree inflammation in IBS and elevated zonulin may contribute to multifactor pathogenesis in IBS.

Faecal calprotectin increases the diagnostic yield in patients with suspected small bowel disease – a multicenter retrospective cohort study

Diagnosing small bowel pathology is challenging, and the diagnostic yield of small bowel capsule endoscopy is highly variable. Faecal calprotectin is a non-invasive intestinal inflammation marker that could be used as a selection tool to identify patients who might benefit from small bowel capsule endoscopy and increase its diagnostic yield. This study aimed to investigate the value of faecal calprotectin in detecting small bowel lesions in an unselected patient population. We performed a retrospective analysis of consecutive patients who underwent small bowel capsule endoscopy at the University Hospital Basel and the University Medical Clinic Cantonal Hospital Baselland, Switzerland, between 2010 and 2018. Patients without faecal calprotectin testing were excluded from the analysis. The primary endpoint was the presence of a clinically significant small bowel finding. Patients with positive faecal calprotectin results were more likely to have small bowel findings (66.7% vs 39.4%;P= 0.007). The optimal faecal calprotectin cut-off to identify clinically significant small bowel lesions was 63 μg/g with 78.3% (95% confidence interval: 66.7-87.9) sensitivity, 47.9% (33.3-62.8) specificity, 1.50 (1.1-2.0) positive and 0.45 (0.3-0.8) negative likelihood ratios, 68.4% (61.6-74.4) positive and 60.5% (47.3-72.4) negative predictive values, and 65.0% overall accuracy. Faecal calprotectin performed best in patients with suspected inflammatory bowel disease, with 66.7% (48.2-82.0) sensitivity, 70.6% (44.0-89.7) specificity, 2.27 (1.0-4.9) positive and 0.47 (0.3-0.8) negative likelihood ratios, 81.5% (67.0-90.5) positive and 54.5% (39.7-68.6) negative predictive values, and 71.4% overall accuracy. Faecal calprotectin testing increases the diagnostic yield of small bowel capsule endoscopy and may help identify patients at risk of small bowel disease.

Both fecal calprotectin and fecal immunochemical tests are useful in children with inflammatory bowel disease.

Noninvasive biomarkers of intestinal inflammation can reduce the number of endoscopies in children with inflammatory bowel disease (IBD). This study aimed to prospectively investigate the usefulness of fecal calprotectin (FCP) and fecal immunochemical test (FIT) in pediatric IBD. Patients aged 6-17years who underwent ileocolonoscopy for established or suspected IBD were eligible for this study. Fecal samples for FCP and FIT were collected before colonoscopy. A total of 251 samples were analyzed: 88 from ulcerative colitis (UC), 74 from Crohn's disease (CD), 75 from healthy controls (HC), and 14 from children with functional gastrointestinal disorders and normal colonoscopy (NC). At IBD diagnosis, both FCP and FIT were significantly higher in the newly diagnosed UC/CD group than in the HC/NC group (P < 0.001). The optimal cutoffs of FCP and FIT to predict IBD diagnosis were 217mg/kg and 87ng/mL, respectively. Patients without mucosal healing (MH) showed higher FCP and FIT than those with MH in both UC and CD (P < 0.001). The FCP increased exponentially as the endoscopic activity score increased. The optimal cutoff values of FCP and FIT for predicting MH were 161mg/kg and 106ng/mL for UC and 367mg/kg and 57ng/mL for CD, respectively. FCP showed better specificity than the FIT. Patients with CD and normal ileocolonoscopy had elevated FCP during active small intestinal inflammation. Both FCP and FIT correlate well with endoscopic activity in pediatric patients with IBD. The FCP is a superior marker for predicting MH.

FECAL CALPROTECTIN TESTING: AN INVESTIGATION OF PATIENT COMPLIANCE AND PERCEPTIONS

Abstract INTRODUCTION Inflammatory Bowel Disease (IBD) is a lifelong illness requiring close management. Prompt disease recognition and tight control of disease activity reduces disease morbidity and improves outcomes1. Endoscopy with histologic examination is the gold standard for assessing “deep remission2.” However, frequent endoscopic evaluation is not always feasible or cost effective. Fecal Calprotectin (FC), a paradigm shifting biomarker, is both sensitive and specific for histologic inflammation in IBD2. However, the efficacy of this test rests on patient’s willingness to handle and submit stool samples. Studies investigating FC non-compliance are scarce, and all have been performed outside the US. Thus, we elected to survey our patients to assess barriers to FC compliance. METHODS We recruited 104 participants with Crohn’s disease (CD) or Ulcerative Colitis (UC) from our IBD clinic to participate in a prospective cross-sectional study. We administered an author-designed mixed-method questionnaire consisting of 23 questions with multiple choice, yes/no, rank order, and open-ended questions. The primary outcomes of interest were risk factors for non-compliance. Patient compliance over a two year period (1/2018 through 1/2020) was self-reported and verified retrospectively by the authors. Responses to questions were grouped according to level of FC compliance (&amp;lt;50% compliance, 50-99% compliance, 100% compliant). Categorical variables were analyzed using chi2 and Fishers exact test. Continuous variables were analyzed using Mann-Whitney and Kruskal-Wallis tests. RESULTS Among the 104 participants surveyed, 56 were always compliant with FC testing (53.8%).The remaining 48 participants fell on a spectrum of compliance, with most participants completing between 50-75% of fecal calprotectin tests over the study period (n=29, 60.4%). Only 8 participants were “never” compliant. Physician determined compliance was significantly associated with participant completion (p=0.001). Number of “no-show” clinic visits was associated with FC compliance (p=0.013). Participants who reported FC testing embarrassing were significantly less likely to be compliant (p=0.037), and were less likely to report that they found stool testing important (p=0.020). In the qualitative portion of the survey, recurring frustrations included inconvenience of testing, embarrassment associated with stool submission, and lack of streamlined sample submission. CONCLUSION Fecal calprotectin is a valuable tool for IBD monitoring, but testing can be cumbersome and usefulness is limited by compliance. Embarrassment was a significant compliance barrier, suggesting that improved education and protocols for laboratory discretion would improve FC submission and patient experience.