Fecal Calprotectin Concentration Research Articles

STANDARDIZATION ISSUES FOR FECAL CALPROTECTIN MEASUREMENT IN INFLAMMATORY BOWEL DISEASE

Fecal calprotectin (FC) is a non-invasive marker of intestinal inflammation that is often used to guide therapeutic decisions in patients with inflammatory bowel disease (IBD). Each step in FC measurement can influence the results, leading to misinterpretation and potentially affecting the management of patients with IBD. To date, FC measurements are highly heterogeneous, and none of the existing methods is generally accepted as a standard. <b>Aim:</b> to provide a clear position on the preanalytical and analytical steps of FC measurement and to minimize the risk of misinterpretation. <b>Materials and methods.</b> A systematic search of the scientific literature was carried out in the PubMed/MEDLINE, EMBASE and Cochrane databases until June 2021 to identify all studies reporting data on FC measurement (for the key phrases "fecal markers of inflammation", "calprotectin", "inflammatory bowel diseases"). <b>Results.</b> Based on available data, quantitative tests should be preferred to measure FC; FC measurements should always be performed using the same method, and factors affecting his levels should be taken into account when interpreting results. <b>Conclusion.</b> FC concentrations determine treatment decisions by physicians. Although FC is playing an increasingly important role in the management of IBD patients, large multicenter studies should be conducted to determine the reproducibility and to confirm the diagnostic accuracy of the available FC tests.

СОДЕРЖАНИЕ КАЛЬПРОТЕКТИНА В СТУЛЕ И ЭОЗИНОФИЛЬНОГО ПРОТЕИНА Х В МОЧЕ У МЛАДЕНЦЕВ В ЗАВИСИМОСТИ ОТ ПОЛИМОРФИЗМА ГЕНОВ ИНТЕРЛЕЙКИНА-10 (G1082A, C592A) И ТОЛЛ-ПОДОБНОГО РЕЦЕПТОРА 4 (ASP299GLY)

Background. Cytokine and toll-like receptor gene polymorphisms may impact oral tolerance formation in infants. Objective: To determine the genotype distribution of IL-10 (G1082A, C592A) and TLR 4 (Asp299Gly) gene polymorphisms in children with different family history of allergy residing in Grodno region; to analyze the association between gene polymorphisms and concentrations of fecal calprotectin (FCP) and urine eosinophil protein X (UEoPX) in infants. Material and Methods. 92 infants were recruited and analyzed for IL-10 (G1082A, C592A) and TLR 4 (Asp299Gly) gene polymorphisms. Concentrations of FCP and UEoPX were examined in dynamics in children aged 1 and 3 months. Results. 80.4% and 48.9% of infants were carriers of the mutant allele of the G1082A and C592A polymorphisms respectively. 70.5% of children with negative family history of allergy were carriers of the wild G allele of G1082A polymorphism. Carriage of the mutant A allele of G1082A polymorphism is associated with lower FCP concentration in infants aged 1 month (AA: 1.9 ng/mL [1.9; 3.1], GA: 15.9 ng/mL [1.9; 93.8]) and GG: 88.3 ng/mL [2.4; 230.1]). The level of UEoPX in 3 months old infants with homozygote AA genotype was significantly (p=0.019) higher than in infants with heterozygote CA genotype (3.2 ng/ml [2.4; 4.5] and 2.3 ng/ml [1.3; 3.3] respectively). Conclusion. Carriage of the wild G allele of G1082A polymorphism is associated with higher fecal calprotectin concentration in one month old infants and significantly lower level of urine eosinophil protein X in 3 months old infants.

P649 Does serum triiodothyronine-to-thyroxine (T3/T4) ratio predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease?

Abstract Background Lower serum free triiodothyronine-to-thyroxine (fT3/fT4) ratio has been linked to non-response to treatment in a range of diseases, including in biologic-treated patients with IBD. We sought to assess whether baseline serum fT3/fT4 ratio predicted primary non-response (PNR) and non-remission to infliximab and adalimumab in patients with Crohn’s disease. Methods We included 997 adult participants from the Personalised Anti-TNF Therapy in Crohn’s Disease study (PANTS). Thyroid function tests, using the Roche Elecsys TSH immunoassay and T3 and T4 electrochemiluminescence assays, were measured on stored baseline samples (prior to biologic treatment). PNR, assessed at week 14, was defined as treatment failure (including IBD-related surgery), ongoing corticosteroid use, or both CRP failing to fall to ≤3 mg/L, or by 50% from baseline, and HBI failing to fall to ≤4, or by 3 points. Non-remission, assessed at week 54, was defined as either CRP of > 3mg/L or HBI of >4 points, ongoing corticosteroid therapy, or exit for treatment failure. Results Serum fT3, fT4 and TSH concentrations were similar in infliximab (n=549) and adalimumab treated (n=448) patients. Baseline median [IQR] fT3/fT4 ratios were lower in women than men (0.30 [0.27 - 0.34] vs 0.32 [0.28 - 0.36], p<0.001), in patients with more severe inflammatory disease, and in patients receiving corticosteroids (0.28 [0.25 - 0.33] vs 0.32 [0.29 - 0.36], p<0.001). Multivariable logistic regression analysis demonstrated that fT3/fT4 ratio was independently associated with PNR at week 14 (OR 0.51, 95% CI 0.31 – 0.85, p = 0.009), however when stratified by drug and adjusted for variables known to be associated with PNR, low fT3/fT4 ratio remained associated with PNR for adalimumab, but not infliximab. After excluding patients treated with corticosteroids at baseline, there was no difference in fT3/fT4 ratio in those who experienced PNR compared to those who did not (PNR: [128/630] 0.31 [0.28 – 0.35] vs no PNR: [502/630] 0.32 [0.29 – 0.36], p = 0.095). The optimal threshold to determine PNR was 0.31 (AUC 0.57 [95% CI 0.54 - 0.61] sensitivity 0.62 [95% CI 0.41 - 0.74], specificity 0.53 [95% CI 0.42 - 0.73]). No association was seen for baseline fT3/fT4 ratio and non-remission or changes in faecal calprotectin concentrations at week 54. Conclusion Lower baseline serum fT3/fT4 ratio was independently associated with female sex, higher inflammatory burden at baseline, and baseline corticosteroid use, and predicted PNR to anti-TNF therapy at week 14, but not non-remission or change in faecal calprotectin concentrations at week 54. Overall, however, the diagnostic accuracy of baseline fT3/fT4 ratio to predict PNR to anti-TNF treatment was modest, limiting its clinical utility.

P244 Prognostic Value of post-biological induction fecal calprotectin concentration on the long-term outcomes of Crohn’s disease

Abstract Background Endoscopy remains the gold standard in Crohn’s disease (CD) to assess mucosal healing but remains invasive and costly. Mucosal healing is the target to reach in current therapeutic strategies because of its association with improve CD outcomes. Fecal calprotectin is still only a surrogate marker due to the lack of data on its ability to predict disease progression. The main objective of this study is to assess whether the value of fecal calprotectin after introduction of biologic is predictive of long-term outcomes of Crohn’s disease. Methods From a prospective database, all patients followed for Crohn’s disease in a tertiary referral center were assessed. We included those in whom fecal calprotectin was measured 3 to 6 months after the introduction of a biologic. Patients were separated into two groups according to the value of fecal calprotectin (more or less than 250 µg/g). Disease outcome was assessed by a composite criterion including: the need for abdominal surgery, progression to complicated phenotype (B2, B3) and a change in therapy due to non-response. Results A total of 198 fecal calprotectin were measured within 3 to 6 months after introduction of biotherapy. Our study population was 61% female (n=120) with a mean age of 39 years. The average duration of the disease was 10 years, 41% (n=82) had never received biotherapy. The treatment initiated was an anti-TNF in 59% of cases (n=117), ustekinumab (n=64; 32%) or vedolizumab (n=17; 9%). A total of 127 (64%) fecal calprotectin were below 250 µg/g. We identified a strong association between postinduction fecal calprotectin value and the long-term outcome in Crohn’s disease patients. Fecal calprotectin was significantly associated with clinical remission without steroids at 1 year from initiation of treatment (p=0,014). In our population, 20 (10%) patients required surgery, 45 (23%) required a change in treatment, 13 (7%) had a change in phenotype and 61 (31%) had at least one of the three events described above. A fecal calprotectin level above 250 µg/g was associated with more abdominal surgery, phenotype and treatment change (HR 2.47 [1.4; 4,36] p:0,0018) (figure 3). In the subgroup of 82 (41%) patients with an available and elevated fecal calprotectine concentration before treatment initiation, the prognostic value of post-induction fecal calprotectin was even better (HR 4,83 [2,02; 11,6] p<0,001) (figure 1). Fecal calprotectin was the only factor significantly associated in uni and multivariate with long-term disease outcome. Conclusion Post induction fecal calprotectin seems to be a good prognostic marker of long-term evolution of Crohn’s disease. These data could lead to limit the use of colonoscopy currently recommended to 6 to 9 months after the start of treatment.

Fecal calprotectin as an indicator in risk stratification of pouchitis following ileal pouch–anal anastomosis for ulcerative colitis

Background Pouchitis is the most common complication following restorative proctocolectomy and ileal pouch–anal anastomosis (IPAA) for ulcerative colitis (UC). Fecal calprotectin (FC) is a noninvasive indicator of the intestinal inflammatory status. This study was conducted to evaluate the clinical value of the FC concentration for the diagnosis and risk assessment of pouchitis. Patients and methods This retrospective study involved patients who underwent IPAA for UC at Tianjin Medical University General Hospital from January 2015 to January 2019. The patients were categorized into pouchitis and non-pouchitis groups based on their Pouchitis Disease Activity Index (PDAI) score. Laboratory indicators, including the FC concentration, were collected from both groups. Results Sixty-six patients with UC after IPAA were included in the study and divided into the non-pouchitis group (n = 40) and pouchitis group (n = 26). The correlation coefficient between the FC concentration and the PDAI score was 0.651 (p < 0.001). Receiver operating characteristic analysis showed that the FC cut-off value for predicting pouchitis was 579.60 μg/g (area under the curve, 0.938). The patients were then divided into three subgroups according to their PDAI score (0–2, 3–6, and ≥7), and significant differences in the FC concentration were found among the three subgroups. The best FC cut-off value for predicting a high risk of pouchitis (PDAI score of 3–6) was 143.25 μg/g (area under the curve, 0.876). Conclusions FC is a useful biomarker in patients with pouchitis. Patients are advised to regularly undergo FC measurement to monitor for pouchitis. An FC concentration in the range of 143.25–579.60 μg/g is predictive of a high risk for pouchitis, and further examination and preventive treatment are necessary in such patients. KEY MESSAGES Fecal calprotectin can be used to quantify pouch inflammation. Fecal calprotectin can be used to predict a high risk of pouchitis.

Fekalni kalprotektin kao marker aktivnosti Kronove bolesti

Introduction. Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) with periods of remission and exacerbation. Numerous studies have been conducted in order to identify the ideal marker when it comes to the inflammatory bowel diseases. In the literature, fecal calprotectin is mentioned as a marker of inflammation. Elevated levels of calprotectin can be detected in stool and they indicate the migration of neutrophils to the intestinal mucosa that occurs with intestinal inflammation. The aim. The main goal of this study was to examine the concentration of fecal calprotectin and CRP depending on the clinical, endoscopic and histological characteristics of patients with Crohn's disease and whether there is a correlation of these markers with disease activity. Methods. The research was conducted in the period from January 2015 to January 2016. The study included subjects who had been diagnosed with Crohn's disease. The study involved 45 respondents, aged 20 - 58 years. All subjects included in the study underwent a colonoscopic examination with biopsy and pathohistological analysis. Fecal calprotectin was determined in one stool sample in all subjects, and that was done quantitatively by a commercial ELISA assay. Determination of serum CRP concentrations was performed in the Central Biochemical Laboratory by standard methods. Results. Fecal concentrations of calprotectin are elevated in all three forms of the disease, while they are significantly higher in moderately severe (545 vs. 218, p ˂ 0.001) and severe forms of the disease (1000 vs. 218, p ˂ 0.001) compared to the mild form. Fecal concentrations of calprotectin are significantly higher at endoscopic grade 3 compared to the other three endoscopic grades (765.3 vs. 314, p ˂ 0.001), (765.3 vs. 392.8, p ˂ 0.001), (765.3 vs. 448.2, p ˂ 0.001). Fecal concentrations of calprotectin are significantly higher in extensive pathological findings compared to normal epithelial surface (1000 vs. 21, p ˂ 0.001) as well as in extensive pathological findings compared to focal pathological findings (1000 vs. 309, p ˂ 0.001). Conclusion. The more severe form of clinical disease activity is accompanied by higher fecal values of calprotectin and higher endoscopic grade, and a more severe histological grade of disease is accompanied by higher fecal values of calprotectin.

Da li je fekalni kalprotektin pouzdan marker kod inflamatornih bolesti creva?

Introduction/Aim: Fecal calprotectin (FCP) is an S100 protein bio-marker used in diagnostic and monitoring algorithms of inflammato-ry bowel diseases (IBD). The role of FCP is established in differentiating inflammatory from functional bowel diseases, predicting relapse of IBD, and monitoring response to IBD therapy. The therapeutic strategy "treat-to-target" includes the normalization of laboratory biomarkers including FCP to attain mucosal healing (MH) as a result of effective Crohn's disease (CD) and ulcerative colitis (UC) treatment. Our research aimed to assess the relationship of FCP values in IBD patients with endoscopic and histological scores of disease activity. Material and methods: We performed a cross-sectional study at the Clinic for Gastroenterohepatology, University Clinical Center of Ser-bia, encompassing 223 diagnosed IBD patients (110 CD and 113 UC). The concentration of FCP was analyzed from the first morning stool. The endoscopic activity of IBD was evaluated using the endoscopic Mayo score for UC, Simple Endoscopic Score (SES-CD) for CD, and Rut-geerts score in case of a prior operation. The Geboes grading score was used to evaluate IBD histological activity. Due to discontinuous bowel involvement in CD, histopathological grading was limited. Results: Our results did not identify any statistically significant relationship between FCP and histological scores in patients with Crohn's disease (FCP median 950.98, PH median 3.57; p= 0.22). While FCP values did not show a correlation with the Rutgeerts score, we did observe a notable correlation between FCP and the SES-CD. In UC patients, values of FCP strongly correlated with endoscopic and his-tological grading (FCP median 1162.62, PH median 3.67; p = 0.011). Conclusion: FCP has shown to be a useful and reliable biomarker for assessing UC disease activity, while its applicability is restricted when it comes to CD.

Перспективный биомаркер интестинального воспаления у больных хронической болезнью почек

The aim of the study was to investigate the content of fecal calprotectin in patients at different stages of chronic kidney disease (CKD). The study included 3 groups of patients: the 1st group included 80 patients with terminal renal failure (TRF) treated by hemodialysis; the 2nd group included 30 patients with S3a-5 CKD (glomerular filtration rate (GFR) 60 ml/min/1.73 m2); the 3rd group included 20 patients with CKD S1-2 (GFR 60 ml/min/1.73 m2 ), comparable by the main clinical and demographic characteristics. The level of fecal calprotectin significantly increased along with the severity of renal failure and reached maximum values in patients on dialysis. In addition, in the groups of patients with moderately severe and severe CKD the concentration of fecal calprotectin was significantly correlated with C-reactive protein (CRP) and the activity of gastrointestinal symptoms (GIS) assessed by the Gastrointestinal Symptoms Questionnaire (GSQ).

Fecal calprotectin - a valuable predictor of microscopic colitis.

Microscopic colitis (MC) has been of major concern worldwide due to its relapsing and remitting nature of chronic diarrhea. Quality of life of patients suffering from this disease is quite debilitating. In order to understand the role and importance of fecal calprotectin (FC) we performed a statistical analysis on the patients suffering from chronic diarrhea and admitted to our hospital from 2014 to 2020, and who were prescribed Loperamide (Imodium) or Budesonide or a combination of both and had undergone FC detection test. FC was found to be significantly correlated to the age, alcohol consumption and beta blocker use. A high level of the FC concentrations increases the chances of having flare-ups of diarrhea episodes making the quality of life of such patients worse. FC concentrations should be monitored frequently and precautionary measures to avoid a relapse should be aimed. Measures to improve quality of life, should be of prime concern. In-depth research is required to better understand MC and to find better treatment options which can be used on a long-term basis, instead of anti-motility drugs which are able to control the acute episodes, but when discontinued result in an increased tendency to have relapses.

Trends of fecal calprotectin levels and associations with early life experience in preterm infants.

Preterm infants are at risk for severe infections due to their immature immune systems. Factors such as early life pain/stress experiences and feeding may influence immune activation and maturation of immune systems. However, the underlying mechanism remains unclear. Fecal calprotectin (FCP) is a noninvasive surrogate biomarker of mucosal inflammation in the gastrointestinal tract and has been used in detecting intestinal inflammation in specific pediatric gastrointestinal disorders. To describe the longitudinal trajectory of FCP levels in preterm infants and investigate the contributing factors that are associated with FCP levels. A longitudinal study design was used. Preterm infants were recruited from 2 neonatal intensive care units (NICU) of a children's medical center in the North-eastern US. Preterm infants were followed during their first 4 weeks of NICU hospitalization. Stool samples were collected twice per week to quantify the FCP levels. Cumulative pain/stress experiences and feeding types were measured daily. A linear mixed-effect model was used to examine the associations between FCP levels and demographic and clinical characteristics, cumulative pain/stress, and feeding over time. Forty-nine preterm infants were included in the study. Infants' FCP levels varied largely with a mean of 268.7±261.3µg/g and increased over time. Preterm infants experienced an average of 7.5±5.0 acute painful procedures and 15.3±20.8 hours of chronic painful procedures per day during their NICU stay. The mean percentage of mother's own milk increased from the first week (57.1±36.5%) to the fourth week (60.7±38.9%) after birth. Elevated FCP concentration was associated with acute and cumulative (chronic) pain/stress levels, mother's own milk, non-White race, and higher severity of illness score. FCP levels were elevated in preterm infants with wide interindividual and intraindividual variations. Cumulative pain/stress during the NICU hospitalization, feeding, race, and health status may influence FCP concentrations in early life that may be associated with inflammatory gut processes.

Ефективність застосування пробіотиків у дітей з синдромом подразненого кишечника: питання оптимальної тривалості лікування

Following the biopsychosocial model of medicine, irritable bowel syndrome (IBS) is a heterogeneous disorder, which is caused by multiple factors in different combinations. However, in most clinical cases probiotics are included in the treatment of IBS due to their influence on intestinal bacterial colonization, and immune, metabolic and motoric activity of the gut. The purpose - to evaluate the efficiency of probiotics (Lactobacillus reuteri DSM 17938) in children with IBS and to determine the optimal duration of the treatment. Materials and methods. We examined 108 children aged 6-12 years with a verified diagnosis of IBS, according to Rome criteria IV. Assessment of the main clinical symptoms was obtained by 4-point Likert scale. Enzyme immunoassay RIDASCREEN Calprotectin (R-Biopharm AG, Germany) was used for the quantitative determination of calprotectin in stool samples. Data were processed using Microsoft Excel 2016 and analysed with GraphPad (Prism 5.0). Results. Our study revealed the heterogenety of IBS in children not only according to clinical subtype, but also due to the trigger factor of the disorder. Patients with stress-related IBS were characterized by the higher level of asthenic syndrome and autonomic dysfunction (р=0.0003). In contrast, children with post-infectious IBS had higher concentration of fecal calprotectin, which is a result of low-grade intestinal inflammation (р=0.0003). After 10 days and 1 month since the beginning of treatment, we have observed a significant decrease in the severity of clinical syndromes, but the level of fecal calprotectin remained elevated. Conclusions. The efficiency of probiotics was confirmed by positive dynamics of clinical signs and the level of fecal calprotectin in children with various clinical subtypes of IBS. Even in the absence of any symptoms, the optimal duration of the use of Lactobacillus reuteri DSM 17938 in children with IBS should be 1-3 months. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

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.

Anti-Inflammatory Effect of Topiramate in a Chronic Model of TNBS-Induced Colitis.

Inflammatory bowel disease (IBD) is characterized by a chronic and relapsing inflammatory response in the gastrointestinal tract, resulting in severe symptoms such as abdominal pain, vomiting, diarrhea, bloody stools, and weight loss. Currently, there is no cure, and the pharmacological treatment includes drugs that induce and keep the patient in remission, not reversing the underlying pathogenic mechanism. These therapies, in the long term, may cause various side effects and complications, which has increased the need to investigate new, more effective, and safer pharmacological approaches. In preclinical studies, topiramate has demonstrated a potential anti-inflammatory effect by inhibiting the production of several pro-inflammatory cytokines. This study aimed to investigate the effect of topiramate in a chronic TNBS-induced colitis model in rodents. Experimental colitis was induced by four intrarectal administrations of 1% TNBS in female CD-1 mice. Topiramate 10 and 20 mg were administered intraperitoneally for 14 days. Several parameters were evaluated, such as bodyweight, alkaline phosphatase (ALP), fecal hemoglobin, fecal calprotectin, tumor necrosis factor (TNF)-α, and interleukin (IL)-10. Topiramate reduces TNBS-induced colonic damage in a model of chronic experimental colitis and normalizes the stool consistency and anus appearance. Additionally, topiramate significantly reduced the concentration of ALP, fecal hemoglobin, fecal calprotectin, TNF-α, and IL-10, demonstrating it to be a promising pharmacological approach for the treatment of IBD in the future.

Sodium Butyrate Effectiveness in Children and Adolescents with Newly Diagnosed Inflammatory Bowel Diseases-Randomized Placebo-Controlled Multicenter Trial.

Background: Butyric acid’s effectiveness has not yet been assessed in the pediatric inflammatory bowel disease (IBD) population. This study aimed to evaluate the effectiveness of oral sodium butyrate as an add-on to standard therapy in children and adolescents with newly diagnosed IBD. Methods: This was a prospective, randomized, placebo-controlled multicenter study. Patients aged 6–18 years with colonic Crohn’s disease or ulcerative colitis, who received standard therapy depending on the disease’s severity, were randomized to receive 150 mg sodium butyrate twice a day (group A) or placebo (group B). The primary outcome was the difference in disease activity and fecal calprotectin concentration between the two study groups measured at 12 weeks of the study. Results: In total, 72 patients with initially active disease completed the study, 29 patients in group A and 43 in group B. At week 12 of the study, the majority of patients achieved remission. No difference in remission rate or median disease activity was found between the two groups (p = 0.37 and 0.31, respectively). None of the patients reported adverse events. Conclusions: A 12-week supplementation with sodium butyrate, as adjunctive therapy, did not show efficacy in newly diagnosed children and adolescents with IBD.

Prognostic Value of Fecal Calprotectin to Inform Treat-to-Target Monitoring in Ulcerative Colitis

We evaluated the value of post-induction fecal calprotectin (FCP) concentration as a biomarker in patients with ulcerative colitis (UC) treated with a biologic. This post hoc analysis of the GEMINI 1/GEMINI LTS (N= 620) and VARSITY (N= 771) trials evaluated the cross-sectional accuracy of post-induction FCP in identifying endoscopic activity and histologic inflammation, and the prognostic performance of FCP in identifying patients most likely to achieve endoscopic and histologic remission or require colectomy and UC-related hospitalization. The cross-sectional accuracy of FCP in identifying endoscopic activity and histologic inflammation was modest (63%-79%). However, a post-induction FCP concentration of ≤250 μg/g vs >250 μg/g was associated with a substantially higher probability of achieving clinical remission (odds ratio [OR], 4.03; 95% confidence interval [CI], 2.78-5.85), endoscopic remission (OR, 4.26; 95% CI, 2.83-6.40), and histologic remission (Robarts Histopathology Index: OR, 5.54; 95% CI, 3.77-8.14; Geboes grade: OR, 6.42; 95% CI, 4.02-10.26) at week 52 and a lower probability of colectomy over 7 years (hazard ratio, 0.296; 95% CI, 0.130-0.677) and UC-related hospitalization (hazard ratio, 0.583; 95% CI, 0.389-0.874). The association with colectomy was significant even among patients in symptomatic remission or with endoscopic improvement post-induction, and among patients with elevated FCP at baseline. Although FCP had only modest cross-sectional accuracy in identifying disease activity, an FCP concentration of ≤250 μg/g vs >250 μg/g was associated with increased probability of achieving long-term clinical, endoscopic, and histologic remission, and reduced probability of colectomy and UC-related hospitalization (ClinicalTrials.gov: NCT00783718, NCT00790933, NCT02497469).

Verification of the fCAL turbo immunoturbidimetric assay for measurement of the fecal calprotectin concentration in dogs and cats.

The concentration of calprotectin in feces (fCal) is a clinically useful marker of chronic gastrointestinal inflammation in humans and dogs. No commercial assay is widely available to measure fCal in small animal medicine, to date. Thus, we verified the immunoturbidimetric fCAL turbo assay (Bühlmann) of fCal for canine and feline fecal extracts by determining linearity, spiking and recovery, and intra-assay and inter-assay variability. We determined RIs, temporal variation over 3 mo, and effect of vaccination and NSAID treatment. Observed:expected (O:E) ratios (x̄ ± SD) for serial dilutions of feces were 89–131% (106 ± 9%) in dogs and 77–122% (100 ± 12%) in cats. For spiking and recovery, the O:E ratios were 90–118% (102 ± 11%) in dogs and 83–235% (129 ± 42%) in cats. Intra- and inter-assay CVs for canine samples were ≤19% and ≤7%, and for feline samples ≤22% and ≤21%. Single-sample RIs were <41 μg/g for dogs and <64 μg/g for cats. With low reciprocal individuality indices, using population-based fCal RIs is appropriate, and moderate fCal changes between measurements (dogs 44.0%; cats: 43.2%) are considered relevant. Cats had significant (but unlikely relevant) fCal increases post-vaccination. Despite individual fCal spikes, no differences were seen during NSAID treatment. The fCAL turbidimetric assay is linear, precise, reproducible, and sufficiently accurate for measuring fCal in dogs and cats. Careful interpretation of fCal concentrations is warranted in both species during the peri-vaccination period and for some patients receiving NSAID treatment.

Understanding anti-TNF treatment failure: does serum triiodothyronine-to-thyroxine (T3/T4) ratio predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn's disease?

SummaryBackgroundDuring illness, adaptations of the hypothalamic–pituitary‐thyroid axis reduce energy expenditure, protein catabolism and modulate immune responses to promote survival. Lower serum free triiodothyronine‐to‐thyroxine (fT3/fT4) ratio has been linked to non‐response to treatment in a range of diseases, including in biologic‐treated patients with inflammatory bowel disease.AimTo assess whether baseline serum fT3/fT4 ratio predicted primary non‐response (PNR) and non‐remission to infliximab and adalimumab in patients with Crohn's diseaseMethodsThyroid function tests were undertaken in stored serum from biologic‐naïve adult patients with active luminal Crohn's disease immediately prior to treatment with infliximab (427 originator; 122 biosimilar) or adalimumab (448) in the Personalised Anti‐TNF Therapy in Crohn's Disease study (PANTS).ResultsBaseline median [IQR] fT3/fT4 ratios were lower in women than men (0.30 [0.27–0.34] vs 0.32 [0.28–0.36], p < 0.001), in patients with more severe inflammatory disease, and in patients receiving corticosteroids (0.28 [0.25–0.33] vs. 0.32 [0.29–0.36], p < 0.001). Multivariable logistic regression analysis demonstrated that fT3/fT4 ratio was independently associated with PNR at week 14 (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.31–0.85, p = 0.009), but not non‐remission or changes in faecal calprotectin concentrations at week 54. The optimal threshold to determine PNR was 0.31 (area under the curve 0.57 [95% CI 0.54–0.61], sensitivity 0.62 [95% CI 0.41–0.74], and specificity 0.53 [95% CI 0.42–0.73]).ConclusionsLower baseline serum fT3/fT4 ratio was associated with female sex, corticosteroid use and disease activity. It predicted PNR to anti‐TNF treatment at week 14, but not non‐remission at week 54.

Predictive value of faecal calprotectin in ulcerative colitis – single centre experience

Objectives Faecal calprotectin is an important biomarker used in the evaluation of inflammatory bowel disease. The aim of this study was to establish the value of faecal calprotectin concentration as a predictor of remission in ulcerative colitis and its correlation with laboratory, endoscopic and clinical findings. Methods The single centre study included 126 adult patients with established diagnosis of ulcerative colitis consecutively visiting our Day clinic from March 2017 to March 2019. We measured serum biomarkers- CRP, haemoglobin, leukocytes and platelets. Faecal calprotectin was determined from stool, and endoscopy was performed with calculation of MAYO endoscopic subscore system (MES 0–1: remission, and MES 2–3: active disease). Clinical assessment was done by using Mayo score for ulcerative colitis (clinical Mayo score <2:remission, >5: active disease).The statistical analysis was performed using an univariate and multivariate model of disease remission prediction using logistic regression. Results According to univariate analysis the increase of faecal calprotectin concentration by 10 ug/g is associated with an 8% decrease in probability of disease remission (OR 0.9921, p < .05). In the multivariate analysis, faecal calprotectin remained a significant predictor of disease remission (OR 0.9948, 95% CI 0.9914–0.9982, p = .0028), however, with a significant contribution of C-reactive protein (OR 0.8340, 95% CI 0.7085–0.9818, p = .0292). According to our model the cut off value for faecal calprotectin was 154 ug/g. Conclusion Our results have shown that faecal calprotectin is an independent predictor of remission in UC patients. The results of our study represent real-life data from a single university centre dealing with FC as a prognostic marker in patients with UC. KEY MESSAGES Faecal calprotectin is an independent predictor of remission in UC patients. Recent studies have suggested that calprotectin correlates well with endoscopic activity of inflammation but correlation of faecal calprotectin in a phase of remission hasn’t been evaluated yet. We have found that other inflammatory biomarkers do not correlate well with either endoscopic or clinical activity in ulcerative colitis.

Effect of chronic and acute enterotoxigenic E. coli challenge on growth performance, intestinal inflammation, microbiome, and metabolome of weaned piglets

Post-weaning enteropathies in swine caused by pathogenic E. coli, such as post-weaning diarrhea (PWD) or edema disease (ED), remain a significant problem for the swine industry. Reduction in the use of antibiotics over concerns of antibiotic resistance and public health concerns, necessitate the evaluation of effective antibiotic alternatives to prevent significant loss of livestock and/or reductions in swine growth performance. For this purpose, an appropriate piglet model of pathogenic E. coli enteropathy is required. In this study, we attempted to induce clinical signs of post-weaning disease in a piglet model using a one-time acute or lower daily chronic dose of a pathogenic E. coli strain containing genes for both heat stable and labile toxins, as well as Shiga toxin. The induced disease state was monitored by determining fecal shedding and colonization of the challenge strain, animal growth performance, cytokine levels, fecal calprotectin, histology, fecal metabolomics, and fecal microbiome shifts. The most informative analyses were colonization and shedding of the pathogen, serum cytokines, metabolomics, and targeted metagenomics to determine dysbiosis. Histopathological changes of the gastrointestinal (GI) tract and tight junction leakage as measured by fecal calprotectin concentrations were not observed. Chronic dosing was similar to the acute regimen suggesting that a high dose of pathogen, as used in many studies, may not be necessary. The piglet disease model presented here can be used to evaluate alternative PWD treatment options.

Intestinal ultrasonography and fecal calprotectin for monitoring inflammation of ileal Crohn's disease: two complementary tests.

Background/AimsTight control of inflammation and adjustment of treatment if activity persists is the current strategy for the management of Crohn’s disease (CD). The usefulness of fecal calprotectin (FC) in isolated involvement of the small intestine in CD is controversial. To assess the usefulness of FC to determine the inflammatory activity detected by intestinal ultrasonography (IUS) in ileal CD. MethodsPatients with exclusively ileal involvement CD who underwent IUS and an FC were prospectively included. Simple ultrasound index was used to determine inflammatory activity. The usual statistical tests for comparison of diagnostic techniques were used. ResultsOne hundred and five patients were included, IUS showed inflammatory activity in 59% of patients and complications in 18.1%. FC showed a significant correlation with IUS in the weak range (Spearman coefficient r=0.502; P<0.001); the area under the receiver operating characteristic curve was 0.79 (95% confidence interval, 0.70–0.88; P<0.001). The FC value that best reflected the activity in IUS was 100 μg/g with sensitivity, specificity, and positive and negative predictive values of 73.0%, 71.4%, 79.3% and 63.8%, respectively. There were no differences in FC concentration between patients with or without transmural complications. The addition of serum C-reactive protein to FC did not improve the ability to assess IUS activity.ConclusionsFC has a significant correlation with IUS to monitor ileal CD activity. This correlation is weak and it does not allow assessing the presence of CD complications. Both tests should be used in conjunction for tight control of ileal CD. More studies on noninvasive tests in this location are needed.