Search

Aims: The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance characteristics of polymerase chain reaction (PCR), interleukin-6 (IL6), and calprotectin of synovial fluid in the diagnosis of PJI., Methods: We performed systematic search of PubMed, Embase, The Cochrane Library, Web of Science, and Science Direct from the date of inception of each database through to 31 May 2021. Studies which described the diagnostic accuracy of synovial fluid PCR, IL6, and calprotectin using the Musculoskeletal Infection Society criteria as the reference standard were identified., Results: Overall, 31 studies were identified: 20 described PCR, six described IL6, and five calprotectin. The sensitivity and specificity were 0.78 (95% confidence interval (CI) 0.67 to 0.86) and 0.97 (95% CI 0.94 to 0.99), respectively, for synovial PCR;, 0.86 (95% CI 0.74 to 0.92), and 0.94 (95% CI 0.90 to 0.96), respectively, for synovial IL6; and 0.94 (95% CI 0.82 to 0.98) and 0.93 (95% CI 0.85 to 0.97), respectively, for synovial calprotectin. Likelihood ratio scattergram analyses recommended clinical utility of synovial fluid PCR and IL6 as a confirmatory test only. Synovial calprotectin had utility in the exclusion and confirmation of PJI., Conclusion: Synovial fluid PCR and IL6 had low sensitivity and high specificity in the diagnosis of PJI, and is recommended to be used as confirmatory test. In contrast, synovial fluid calprotectin had both high sensitivity and specificity with utility in both the exclusion and confirmation of PJI. We recommend use of synovial fluid calprotectin studies in the preoperative workup of PJI. Cite this article: Bone Joint J  2022;104-B(3):311-320.

Background: Calprotectin is a calcium-binding protein that can be measured in serum, plasma, and feces. Increased serum and plasma calprotectin concentrations have been found in chronic inflammatory rheumatic disorders. An analytical and clinical evaluation of the DiaSorin Liaison® fecal Calprotectin assay using LIAISON® XL was performed., Methods: The protocol included an analytical and clinical evaluation in which imprecision, the linearity of dilution, differences between serum and plasma samples and method comparison with CalproLab™ ELISA kit were assessed. Serum calprotectin concentrations in active (n = 26) and remission (n = 23) rheumatoid arthritis (RA) patients were compared., Results: The intra-day and inter-day analytical imprecision CVs ranged from 2.9% to 4.0% and 2.7% to 10.4%, respectively. Correlation between measured and expected values was high (R > 0.99), indicating good linearity. The Wilcoxon signed-rank test showed that serum and plasma matched samples presented statistically significant differences (p < 0.001) being the highest concentrations of calprotectin observed in serum samples. Deming regression equation was as follows: Diasorin calprotectin (μg/ml) = -0.32 (95% CI: -0.65 - -0.05) +1.58 (95% CI: 1.42-1.79).* Calprolab calprotectin (μg/ml). Significantly higher serum calprotectin levels were found in RA patients with active disease when compared to patients with low disease activity or in clinical remission (mean ± SD) [(3.35 μg/ml ± 1.55) vs. (1.63 μg/ml ± 0.52), p < 0.001] and these levels correlated well with all disease activity indices., Conclusions: The DiaSorin Liaison® fecal Calprotectin assay adapted for serum samples showed adequate technical performances and the clinical performances were similar to other assays., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Aims and Methods: Faecal calprotectin (FCP) measurement is used especially to investigate for inflammatory bowel disease (IBD). To assess the utility of sampling endoscopically normal large bowel among patients first presenting with elevated FCP, this study identified 115 such patients out of 652 patients with elevated FCP from approximately 6000 primary care tests processed over 15 months., Results: 23 cohort patients showed histologically abnormal large bowel biopsies. Only four cases demonstrated acute inflammation and two such patients only showed scattered cryptitis and did not develop IBD. A third patient demonstrated similar histology but, following repeat colonoscopy, her elevated FCP was attributed to small intestinal inflammation. Only the fourth patient's large bowel biopsies showed features suggesting Crohn's disease, but this represented an IBD detection rate out of 115 sets of large bowel biopsies of 0.9%., Conclusions: Sampling of endoscopically normal large bowel among patients first presenting with elevated FCP is not clinically justified., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Endoscopy remains the gold standard for evaluating postoperative recurrence in Crohn's disease. Timely therapy adjustment according to endoscopic findings can improve long-term outcomes., Objective: We aimed to determine the characteristics, clinical values, and safety of the endoscopic evaluation at 1 month after surgery., Design: This was a prospective observational study., Settings: This study was conducted in a tertiary referral hospital., Patients: Patients with Crohn's disease undergoing ileocolic resection between January 2016 and November 2018 were included., Interventions: The first postoperative ileocolonoscopy was performed at 4-5 weeks after surgery., Main Outcome Measures: The primary outcome was postoperative recurrence within 12 months after surgery. Univariate and multivariate analyses were performed to identify risk factors., Results: Among 84 ileocolonoscopies at 4-5 weeks, no endoscopic complication occurred. The main endoscopic findings at the first evaluation were anastomotic circumferential ulcers (10, 11.9%), anastomotic scattered ulcers (35, 41.7%), ulcers in the neoterminal ileum (16, 19.0%), edema in anastomosis (50, 59.5%), mild narrowing in anastomosis (7, 8.3%), and mild narrowing in neoterminal ileum (3, 3.6%). Anastomotic scattered ulcers were associated with future postoperative recurrence (OR, 2.532 (95% CI, 1.02-6.32), p = 0.046). Fecal calprotectin >150 ug/g on postoperative day 14 could predict anastomotic scattered ulcers (OR' 2.91 (95% CI, 1.31-7.47), p = 0.027). The modified Rutgeerts score was used to define endoscopic findings: i0, 37 (44.0%); i1, 4 (4.8%); i2a, 29 (34.5%); i2b, 11 (13.1%); i3, 0; i4, 3 (3.6%). Score ≥i2a were associated with future postoperative recurrence (OR, 3.17 (95% CI, 1.22-8.27), p = 0.018). No factor was associated with a Rutgeerts score of ≥i2a at the first endoscopic evaluation., Limitations: This was a single-center study with a small cohort of patients., Conclusions: Endoscopic evaluation at 1 month after surgery in CD was safe. Anastomotic scattered ulcers occurred in nearly half of patients and were associated with future postoperative recurrence. See Video Abstract at http://links.lww.com/DCR/B760.LA EVALUACIÓN ENDOSCÓPICA A UN MES DESPUÉS DE LA RESECCIÓN ILEOCÓLICA PARA LA ENFERMEDAD DE CROHN, PREDICE FUTURA RECURRENCIA POSOPERATORIA Y ES SEGURAANTECEDENTES:La endoscopia sigue siendo el estándar de oro para evaluar la recurrencia posoperatoria en la enfermedad de Crohn (EC). El ajuste oportuno en la terapia de acuerdo con los hallazgos endoscópicos, puede mejorar los resultados a largo plazo.OBJETIVO:Determinar las características, valores clínicos y seguridad de la evaluación endoscópica, al mes de la cirugía.DISEÑO:Estudio observacional prospectivo.ENTORNO CLINICO:El estudio se llevó a cabo en un hospital de referencia terciario.PACIENTES:Se incluyeron pacientes con EC sometidos a resección ileocólica entre enero de 2016 y noviembre de 2018.INTERVENCIONES:La primera ileocolonoscopia posoperatoria se realizó a las 4-5 semanas posteriores a la cirugía.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la recurrencia posoperatoria dentro de los 12 meses posteriores a la cirugía. Se realizaron análisis univariados y multivariados para identificar factores de riesgo.RESULTADOS:Entre 84 ileocolonoscopias a las 4-5 semanas, no ocurrió ninguna complicación endoscópica. Los principales hallazgos endoscópicos en la primera evaluación, fueron úlceras anastomóticas circunferenciales (10, 11,9%), úlceras anastomóticas dispersas (35, 41,7%), úlceras en el íleon neo-terminal (16, 19,0%), edema en la anastomosis (50, 59,5%), estrechamiento leve en la anastomosis (7, 8,3%) y estrechamiento leve en el íleon neo-terminal (3, 3,6%). Las úlceras anastomóticas dispersas se asociaron con recurrencia posoperatoria futura (OR, 2,532 (95% CI, 1,02-6,32), p = 0,046). La calprotectina fecal en el post d 14 > 150 ug / g podría predecir úlceras anastomóticas dispersas (OR' 2,91 (95% CI, 1,31-7,47), p = 0,027). Se utilizó la puntuación de Rutgeerts modificada para definir los hallazgos endoscópicos: i0, 37 (44,0%); i1, 4 (4,8%); i2a, 29 (34,5%); i2b, 11 (13,1%); i3, 0; i4, 3 (3,6%). La puntuación ≥i2a se asoció con recurrencia posoperatoria futura (OR, 3,17 (95% CI, 1,22-8,27), p = 0,018). Ningún factor se asoció con ≥i2a en la primera endoscopia.LIMITACIONES:Estudio de un solo centro con una pequeña cohorte de pacientes.CONCLUSIONES:La evaluación endoscópica al mes de la cirugía en EC, fue segura. Se produjeron úlceras anastomóticas dispersas en casi la mitad de los pacientes y se asociaron con una futura recurrencia posoperatoria. Consulte Video Resumen en http://links.lww.com/DCR/B760. (Traducción - Dr. Fidel Ruiz Healy)., (Copyright © The ASCRS 2022.)

Early diagnosis of colorectal advanced neoplasms (ANs), including colorectal cancer (CRC) and advanced adenoma (AA), has a positive effect on the survival rate. As a first attempt, the aim of this meta-analysis was to compare the diagnostic accuracy of faecal protein biomarkers for the detection of colorectal neoplasms with consideration of a wide range of covariates. A systematic literature search was performed up to Jun 10, 2021 on Web of Sciences, Scopus and PubMed. The diagnostic accuracies were calculated using the bivariate/hierarchical random effect model. Biomarkers were determined to be clinically applicable (CA) if they had areas under the curve > 0.70 and positive and negative likelihood ratios > 2 and < 0.5, respectively. A total of 47,059 test results were extracted from 16 immunochemical faecal occult blood test (iFOBT), 26 pyruvate kinase-M2 (PK-M2) and 23 faecal calprotectin (FC) studies. Only iFOBT, PK-M2 and FC for CRC plus iFOBT and PK-M2 for AN were CA. iFOBT had significantly superior accuracy (P = 0.02 versus PK-M2 and P < 0.01 versus FC for CRC; P < 0.01 versus PK-M2 for AN). Regarding covariates, the lateral flow method of PK-M2 measurement increased its accuracy for CRC detection compared to the enzyme-linked immunosorbent assay (P < 0.01). iFOBT is recommended as the most accurate faecal biomarker for CRC and AN diagnosis., (© 2022. The Author(s).)

Objectives: To compare the PhiCal assay (CALPRO), the first US Food and Drug Administration-approved assay for fecal calprotectin, to 4 next-generation assays., Methods: Stool samples from 50 patients were selected, and relevant clinical information was collected. Comparisons were performed using the PhiCal, fCAL turbo (BÜHLMANN), LIAISON Calprotectin (DiaSorin), QUANTA Lite Calprotectin ELISA (Inova Diagnostics), and Calprotectin Chemiluminescence ELISA (ALPCO) assays., Results: All 4 assays had acceptable agreement with PhiCal when qualitatively categorizing results. Within the PhiCal reportable range of 16 to 1,250 μg/g, the DiaSorin, Inova Diagnostics, and ALPCO assays had Spearman correlation coefficients of 0.98, 0.97, and 0.95 and positive biases of 17%, 20%, and 15%, respectively. The BÜHLMANN assay ran approximately 2-fold higher than the PhiCal assay but had a correlation coefficient of 0.98, with similar result categorization., Conclusions: Our results demonstrate good comparison between PhiCal and 4 next-generation assays. Laboratories performing fecal calprotectin assays may have compelling reasons to adopt next-generation fecal calprotectin testing, such as greater automation, a decreased number of replicates needed per test, and the use of stool-extraction devices. These benefits could decrease turnaround times and lower costs. Although the results of the assays correlated, they are not standardized. Laboratories adopting the newer assays will need to further investigate their performance through validation studies., (© American Society for Clinical Pathology, 2021. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Currently used endoscopic items for the assessment of pouchitis and cuffitis have deficiencies in reliability and validation. We assessed the reliability and accuracy of new endoscopic items for pouchitis and of the Ulcerative Colitis Endoscopic Index of Severity [UCEIS] for cuffitis., Methods: Three new endoscopic items were assessed and included in the Monash pouchitis endoscopic subscore: bleeding [absent/contact/spontaneous]; erosions [absent/<10/≥10]; and ulceration [absent/<10%/≥10%]. Three raters evaluated 44 pouchoscopy videos in duplicates, in random order. Intra- and inter-rater reliability of all endoscopic items and UCEIS were assessed. Clinical and histological pouchitis disease activity index [PDAI] subscores were also assessed and faecal calprotectin was measured., Results: All three Monash endoscopic items had substantial intra-rater reliability with intraclass correlation coefficients [ICCs] >0.61 [95% CI >0.61], compared with only ulcers from the currently used PDAI endoscopic subscore, but inter-rater reliability was only substantial for ulceration and no better than those of the currently used endoscopic items. The Monash endoscopic subscore had a strong positive correlation with the reference standard global endoscopic lesion severity r = 0.80 [95% CI 0.80-0.80] and the reference standard PDAI endoscopic subscore r = 0.70 [95% CI 0.67-0.73], which was higher than the correlation observed for the currently used PDAI endoscopic subscore. The UCEIS had substantial intra-rater reliability, but only fair inter-rater reliability and poor diagnostic performance for cuffitis., Conclusions: The Monash endoscopic items, and endoscopic subscore they generate, have enhanced overall performance compared with the currently used PDAI items and subscore. Further validation and responsiveness to change in disease state are indicated., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: In symptomatic patients with ileoanal pouches, pouchoscopy is needed for accurate diagnosis but is invasive. We aimed to assess the utility of non-invasive gastrointestinal ultrasound and faecal calprotectin in ileoanal pouch patients., Methods: Patients with an ileoanal pouch were consecutively enrolled in this cross-sectional study from clinics in Victoria, Australia. The pouchitis disease activity index was used as a reference standard. Video-recorded pouchoscopies were reviewed by three gastroenterologists. Pouch, pre-pouch, and cuff biopsies were reviewed by a single pathologist. Ultrasound was performed by a single gastroenterologist transabdominally and transperineally. Faecal calprotectin was measured from morning stool samples. All examiners were blinded to patients' clinical history., Results: A total of 44 participants had a pouchoscopy, of whom 43 had a faecal calprotectin test and 42 had an ultrasound; 17 had pouchitis, 15 had pre-pouch ileitis, and 16 had cuffitis. Pouch wall thickness of <3 mm was 88% sensitive in excluding pouchitis, and pouch wall thickness of ≥4 mm was 87% specific in diagnosing pouchitis. Transabdominal ultrasound had good utility [area under the curve: 0.78] in diagnosing moderate-severe pre-pouch ileitis. Transperineal ultrasound had good utility for the diagnosis of pouchitis [area under the curve: 0.79]. Faecal calprotectin differentiated inflammatory from non-inflammatory pouch disorders, such as irritable pouch syndrome, with an area under the curve of 0.90. Faecal calprotectin <100 µg/g ruled out inflammatory pouch disorders with a sensitivity of 94%., Conclusions: Faecal calprotectin and ultrasound are accurate and complementary tests to diagnose and localise inflammation of the ileoanal pouch. Prospective studies are needed to validate proposed sonographic indices and calprotectin levels., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Backgrounds and Aims: Inflammatory bowel disease (IBD) patients often experience disease flare-ups during international air travel. We aimed to identify risk factors associated with IBD flare-up during international air travel., Methods: Patients with scheduled international air travel were enrolled in the study from the Seoul National University Bundang Hospital IBD clinic. Flight information and clinical data were collected via questionnaires and personal interviews, and risk factors associated with IBD flares were determined., Results: Between May 2018 and February 2020, 94 patients were prospectively enrolled in the study (mean age, 33.0 years; males, 53.2%; mean disease duration, 56.7 months), including 56 (59.6%) with ulcerative colitis and 38 (40.4%) with Crohn's disease. Of the 94 patients enrolled, 15 (16.0%) experienced an IBD flare-up and 79 (84.0%) remained in remission throughout travel. Logistic regression analysis revealed that high fecal calprotectin levels before travel (odds ratio [OR]: 1.001, 95% confidence interval [CI]: 1.000-1.001, p = 0.016), the presence of a comorbidity (OR: 6.334, 95% CI: 1.129-35.526, p = 0.036), and history of emergency room visit (OR: 5.283, 95% CI: 1.085-25.724, p = 0.039) were positively associated with disease flare-up. The previous and current use of immunomodulators and biologics, time of flight, altitude, number countries visited, travel duration, objective of visit, and previous medical consultations were not associated with disease flare-up., Conclusions: Elevated fecal calprotectin levels, history of emergency room visits, and the presence of a comorbidity predicted IBD flare-up during international air travel., Competing Interests: NO authors have competing interests.

Micro-inflammation in the gut, assessed by fecal calprotectin (FC), is considered a component of the pathogenesis of functional diarrhea (FD). Since probiotics may suppress micro-inflammation in the intestine by competing with harmful bacteria, we hypothesized that they would reduce the ratio of loose stool symptoms and gut inflammation in patients with FD. We conducted a double-blind, placebo-controlled trial to assess the clinical and laboratory effects of Lactobacillus plantarum CJLP243 in FD patients with elevated FC levels for two months. Twenty-four patients diagnosed with FD with elevated FC levels were randomly assigned to either a probiotic group or a placebo group. After 2 months, 10 patients in the probiotic group and 12 patients in the placebo group completed the study, and FD symptoms, FC values, and intestinal flora were re-evaluated in these subjects. The percentage of subjects who had adequate FD relief (decrease in loose stool frequency) in the probiotic group was significantly increased after two months compared with the baseline. In addition, the probiotic group showed a statistically significant decrease in log-transformed FC values compared with the pre-treatment group, whereas the placebo group showed no difference before and after the intervention. Furthermore, the levels of Leuconostoc genus organisms in the gut microbiota composition in the probiotic group increased significantly after the end of the study compared with the baseline values. In this preliminary exploratory research, we found that two months of Lactiplantibacillus plantarum CJLP243 treatment resulted in FD symptom improvement, reduced FC values, and increased Leuconostoc levels, suggesting that the intake of Lactiplantibacillus plantarum was helpful in those patients. These findings need to be validated via further clinical studies.

Background/aims: : Although 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., Methods: This 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., Results: A 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)., Conclusions: FC 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.

Background: Periprosthetic joint infections (PJI) are a rare but severe complication of total joint arthroplasty (TJA). However, the diagnosis of PJI remains difficult. It is one of the research that focuses about diagnosis for PJI for majority researchers to discover a novel biomarker. This meta-analysis tried to evaluate diagnostic value of synovial calprotectin for PJI., Methods: This meta-analysis search of the literature was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library. Literature quality was appraised using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) based on RevMan (version 5.3). The diagnostic value of calprotectin for PJI was evaluated by calculating sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), diagnostic score and area under SROC (AUC) based on the Stata version 14.0 software. We conduct subgroup analysis according to the study design, cutoff values, the country of study, and gold standard., Results: Seven studies were included in this meta-analysis. The pooled sensitivity of synovial calprotectin for the diagnosis of PJI was 0.94 (95% CI, 0.87-0.98), and the specificity was 0.93 (95% CI, 0.87-0.96). The pooled AUC, PLR, and NLR for synovial calprotectin were 0.98 (95% CI, 0.96-0.99), 13.65 (95% CI, 6.89-27.07), and 0.06 (95% CI, 0.02-0.15), respectively. The pooled diagnostic score and DOR were 5.4 (95% CI, 3.96-6.85) and 222.32 (95% CI, 52.52-941.12), respectively., Conclusion: In summary, this meta-analysis indicates that synovial calprotectin is a promising biomarker of assistant diagnosis for PJI, as well as recommended test for excluding diagnostic tool., (© 2021. The Author(s).)

Objective: Intestinal ultrasound is considered to be a valid alternative for the evaluation of post-operative recurrence (POR) of Crohn's disease. The aim of this study is to assess the correlation between ultrasound and endoscopic findings., Methods: Patients with Crohn's disease were retrospectively recruited who had undergone ileocecal resection, and for whom a colonoscopy and intestinal ultrasound had been performed for the detection of POR. Recurrence was assessed using the Rutgeerts score (RS). The ultrasound findings analysed were bowel wall thickness (BWT), parietal hyperaemia using power Doppler, loss of layer pattern and mesenteric fat hypertrophy., Results: A total of 31 patients were included, of which 15 (48.4%) had no POR (RS<2b) and 16 (51.6%) had POR (RS≥2b). A statistically significant association was identified between BWT and the presence of endoscopic recurrence (a mean of 2.75mm vs. 5.68mm, P>0.001). There was also a statistically significant difference in hyperaemia between the 2groups (P=0.03). For wall thickness, an area under the ROC curve (AUC) of 92.9% was obtained, and with a cut-off point of 3.4mm, a sensitivity of 100% and specificity of 86.6%. When comparing with the most frequent biomarkers (fecal calprotectin and serum CRP), a higher AUC was obtained for wall thickness (72.3% and 72.3% vs. 92.9%)., Conclusions: In our experience, ultrasound has high diagnostic efficacy in the detection of POR and can be considered a valid non-invasive alternative to endoscopy., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

The results of animal studies and clinical data support the gut microbiota contribution to the pathogenesis of Alzheimer's disease (AD). The aim of this pilot study was to evaluate the prevalence of small intestinal bacterial overgrowth (SIBO) and fecal markers of intestinal inflammation and permeability in AD patients. The study was conducted in 45 AD patients and 27 controls. Data on comorbidities, pharmacotherapy, and gastrointestinal symptoms were acquired from medical records and a questionnaire. SIBO was evaluated using lactulose hydrogen breath test. Fecal calprotectin and zonulin levels were assessed by ELISA assays. The positive result of SIBO breath test was found in 49% of the AD patients and 22% of the controls (p = 0.025). The comparative analysis between SIBO-positive and SIBO-negative AD patients with respect to the degree of cognitive impairment, comorbidities and used medications did not reveal any statistically significant difference, except for less common heartburn in SIBO-positive AD patients than in SIBO-negative ones (9 vs 35%, p = 0.038). The median fecal calprotectin and zonulin levels in the AD group compared to the control group amounted to 43.1 vs 64.2 µg/g (p = 0.846) and 73.5 vs 49.0 ng/ml (p = 0.177), respectively. In the AD patients there was no association between the presence of SIBO and fecal calprotectin level. Patients with AD are characterized by higher prevalence of SIBO not associated with increased fecal calprotectin level that may be related to anti-inflammatory effect of cholinergic drugs used in the treatment of AD., (© 2021. The Author(s).)

Background: Fecal calprotectin (fCal) is an important surrogate biomarker of chronic inflammatory bowel disease (IBD): Crohn's disease and ulcerative colitis. Non-invasive, immunochromatographic rapid tests are excellent tools for the real-time monitoring of disease activity and reduce the need for invasive and costly colonoscopy procedures., Methods: In this study the accuracy of fCal detection by the semi-quantitative Actim® Calprotectin and the quantitative automated LIAISON® Calprotectin assay was assessed on a panel of clinical stool samples., Results: Of the 119 fecal samples tested, Actim® Calprotectin agreed on 94 samples (79.0%) with the reference test. Furthermore, of the positive samples detected with LIAISON® Calprotectin, 94.0% were interpreted as positive by Actim® Calprotectin., Conclusions: Actim® Calprotectin is a rapid test that can be utilized for the initial differentiation between negative and positive samples in an outpatient setting, thus helping to limit more laborious quantitative methods to positive samples.

Introduction: While fecal calprotectin (FC) is used to assess disease activity in ulcerative colitis (UC) there are little data concerning the role of serial FC levels at diagnosis in predicting clinical course. We sought to determine whether FC at diagnosis or early change following therapy predicts clinical outcomes in pediatric UC.Methods: Children with newly diagnosed UC were treated with standardized regimens of mesalamine or corticosteroids (CS). CS tapering and escalation to additional therapy or colectomy were by protocol. Patients with baseline or week 4 or week 12 FC levels were included in the analysis. Our primary outcome was CS-free remission on mesalamine at week 52. We compared the prognostic value of a baseline FC as well as a change in FC by week 4 or week 12 in predicting clinical outcomes., Results: The study included 352 children (113 initial mesalamine, 239 initial CS, mean age 12.6 years) with UC. At Week 52, 135 (38.3%), 84 (23.8%), and 19 (5.4%) children achieved CS-free remission, needed anti-tumor necrosis factor therapy or had colectomy respectively. Baseline FC was not associated with CS-free remission at week 52. However, both week 4 (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.901.00) and week 12 FC levels (OR 0.91, 95% CI 0.87-0.96) were associated with outcomes, with the latter having a stronger association with CS-free remission. Patients with a >75% decrease by 12 weeks, had a 3-fold increased likelihood of CS-free remission at 1 year., Discussion: Longitudinal changes in FC may predict 1 year outcomes better than values at diagnosis in children with a new diagnosis of UC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: monocytes play an important role in the pathogenesis of inflammatory bowel disease but data are scarce regarding activity biomarkers, above all in patients under biologic therapies., Objective: the aim of this study was to evaluate the value of monocyte measurements in predicting flares in inflammatory bowel disease patients under maintenance treatment with anti-TNF., Methods: a prospective, observational cohort study was designed. Relapse was defined as a Harvey-Bradshaw score > 4 in Crohn's disease, and a partial Mayo score ≥ 2 in ulcerative colitis. Monocyte concentration was quantified at 4-month intervals for twelve months. A total of 95 consecutive patients were included. Median age was 42 years, 50.5 % were female, and 75 % had Crohn's disease., Results: sixteen months after inclusion, 65 (68.4 %) patients remained in clinical remission. Mean monocyte count preceding a relapse was 563 (standard deviation: 144) compared to 405 (standard deviation: 177) in patients who remained in remission. Final monocyte count was significantly different between relapse and remission in Crohn's disease (0.82; 95 % CI: 0.71-0.90; p < 0.005). According to the multivariate analysis, only monocytes and fecal calprotectin were related to more relapses., Conclusion: in conclusion, in inflammatory bowel disease patients under anti-TNF therapy, repeat monocyte counts could help monitor patients, at least in Crohn's disease.

Aim: Most patients with ulcerative colitis (UC) with active mucosal disease have a lower C-reactive protein (CRP) level than the classic accepted cutoff level (≤5 mg/l). We aimed to predict the mucosal remission in UC with an optimal cutoff level of CRP when mucosal activity and extensiveness of UC were both considered., Method: In this retrospective study, we evaluated CRP values and their relation to mucosal extension and UC activity in 331 colonoscopic examinations performed between December 2016 and March 2019. Endoscopic activity and disease extension were assessed using Mayo scores and the Montreal classification., Results: The Mayo 2 and 3 groups' CRP values were significantly higher when compared with Mayo 0-1 between values of E1 and both E2 and E3 with an increasing trend. The standard CRP cutoff level ≤5 mg/l only yielded 55% specificity in predicting mucosal remission. In the ROC analysis, a CRP cutoff level ≤2.9 mg/l predicted an overall mucosal remission (Mayo 0-1) with 77% sensitivity and 80% specificity, and ≤1.9 mg/l predicted Mayo-0 with 70% sensitivity and specificity. In the clinical remission subgroup, the overall CRP cutoff level was even lower, at ≤1.58 mg/l., Conclusion: An overall CRP cutoff level ≤2.9 mg/l predicts mucosal remission in UC better than the standard cutoff ≤5 mg/l. Mucosal remission in stable clinical remission may present with an even lower CRP level. An increasing trend in the CRP level from E1 through E3 even in mucosal remission suggests that both histological inflammation and extensiveness may have some influence on a CRP-based prediction of endoscopic remission., (© 2021 The Association of Coloproctology of Great Britain and Ireland.)

Aim: To conduct comparative analysis of histological remission in patients with moderate and severe ulcerative colitis (UC), receiving biological therapy vedolizumab, mesenchymal stem cell (MSC) treatment and combined stem cells and vedolizumab therapy., Materials and Methods: We studied biopsies of 75 patients with total or left-sided moderate and severe ulcerative colitis, divided into groups depending on treatment. The first group of UC patients (n=29) received stem cell therapy 2 mln per kg; the second group of UC patients (n=27) received vedolizumab and the third group (n=19) MSC and vedolizumab. The efficacy of treatment was assessed by C reactive protein (CRP), Mayo score (MS), fecal calprotectin (FC) and Geboes score (GS)., Results: We determined medium correlation between basic FC and MS before treatment (r=0.6605, p0.05). After 12 weeks of treatment in the first group of UC patients (n=29) CRP was 7.82.1 mg/l, FC 409.344.85 g/g, medium GS 1.20.1 points. After 12 weeks of treatment in the second group of UC patients (n=27) CRP was 8.41.4 mg/l, FC 435.547.3 g/g, medium GS 1.350.15 points. After 12 weeks of treatment in the third group of UC patients (n=19) CRP was 6.41.1 mg/l, FC 290.617.5 g/g, medium GS 0.90.1 points. We proved strong direct relationship between FC and GS after 12 weeks of treatment in UC patients, receiving MSC (r=0.8392, p0.05). The statistically significant majority of patients, achieved histological remission, have less than 5-year duration of disease., Conclusion: Our study showed that clinical and endoscopic remission in UC patients does not always correlate with histological remission. Combined anti-cytokine and stem cells therapy contributes to achieve deep remission and decrease mucosa inflammation rather than single MSC or vedolizumab treatment. Deep remission could be achieved by earlier start of biological therapy. FC could be a predictor and marker of mucosa healing and histological remission.

Aims: The home-performed fecal calprotectin (FC) test has been proposed for the remote management of inflammatory bowel disease (IBD) patients. We present our real-world experience on the use of FC home testing in IBD patients under maintenance treatment with adalimumab., Methods: Consecutive IBD patients on maintenance treatment with adalimumab were studied retrospectively on the basis of prospectively recorded data. FC calprotectin home test (IBDoc, Βühlmann Laboratories AG, Schönenbuch, Switzerland) was analyzed alongside sufficient information on baseline characteristics, follow-up data and treatment modifications, as well as serum biomarkers and endoscopic assessment data on the basis of validated endoscopic scores., Results: From a total of 72 IBD patients under maintenance treatment with adalimumab, 65 (90%) showed compliance with performing the home FC test. FC values were significantly higher in patients who finally needed treatment modification (37%) compared with those who were maintained on stable treatment (63%) (761 μg/g [537-1000] vs. 108 [41-335], P < 0.0001). In the logistic regression analysis FC and erythrocyte sedimentation rate (ESR) were independently correlated with endoscopically active disease (odds ratio: 1.003; 95% confidence interval, 1.001-1.006, P < 0.01 and odds ratio: 1.058; 95% confidence interval, 1.013-1.105, P < 0.05). FC identified patients with endoscopically active disease more effectively than other biomarkers with an area under the receiver operating characteristic curve of 0.78. FC levels >413 μg/g had a sensitivity of 75% and a specificity of 76% in predicting active disease in endoscopy., Conclusions: These first real-life results indicate that in IBD patients under maintenance treatment with adalimumab FC home test is a valuable tool with high compliance rates that performs better than the other biomarkers in predicting disease endoscopic activity., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aims: In Crohn's disease (CD) few data are available on the usefulness of monitoring fecal calprotectin (FC) in the early postoperative setting. We assessed prospectively the accuracy of FC measured 3 months after surgery to predict the risk of endoscopic postoperative recurrence (POR) within 1 year after resection., Methods: In 55 consecutive CD patients who had undergone ileocolonic resection samples were collected 3 months after surgery for measuring serum CRP and FC. Endoscopic POR was assessed by ileocolonoscopy within 6-12 months (median 7 months). Receiver operating characteristic (ROC) curves were generated to assess accuracy of the markers, to determine the best threshold and to calculate sensitivity, specificity, positive and negative predictive values., Results: In contrast with median CRP levels, median FC concentrations measured 3 months after surgery were significantly higher in patients who later experienced endoscopic POR (Rutgeerts ≥ i2) compared with those who stayed in endoscopic remission within the following 6-12 months (205 μg/g IQR [106-721] vs. 103 μg/g IQR [60-219], p = 0.008). Area under the ROC curve for FC was 0.71. The best cutoff value of FC to identify patients in subsequent endoscopic remission 3 months after surgery was 65 μg/g (96% sensitivity, 31% specificity, 50% positive and 91% negative predictive values). In multivariate analysis, FC < 65 µg/g at 3 months was the only factor associated with subsequent endoscopic remission., Conclusion: FC measured 3 months after surgery below 65 μg/g is an accurate marker to identify CD patients who will later stay in endoscopic remission within 1 year after resection., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

The hypothesis of the study was that polymorphisms in promoter regions -238 and -308 of TNF-α could be associated with different clinical outcomes in inflammatory bowel diseases (IBD) and immune-mediated rheumatic diseases (IMRD). The aim was to examine the possible association of both polymorphisms with concentration of C-reactive protein (CRP) and fecal calprotectin (fCAL), onset of the remission and development of the ADA in patients on therapy with anti-TNF inhibitors. The prospective study was done in patients with IBD and IMRD on infliximab (IFX) or adalimumab (ADM). Patients were genotyped for TNF-α -238 and -308 polymorphisms. The concentration of CRP, fCAL, IFX or ADM and antibodies to drugs were measured according to manufacturer's instructions and followed-up for 6 or 12 months. Out of all patients (N = 112), number of patients in remission did not differ according to genotypes (for IBD patients P = 0.509 vs 0.223; for IMRD patients P = 0.541 vs 0.132 for TNF-α -238 and -308, respectively). Initial CRP concentration was higher in IBD patients with TNF-α -308 GG than GA/AA genotypes in patients who failed to achieve remission [11.8 (4.4-39.6) vs 3.1 (1.5-6.5), P = 0.033]. In IBD patients with remission, fCAL concentration after at least 6 months of therapy was higher in TNF-α-308 GG than in GA genotype [52 (25-552) vs 20 (20-20) µg/g, P = 0.041]. Our results showed the association of TNF-α -308 GG genotype with a higher concentration of CRP and fecal calprotectin in patients with inflammatory bowel diseases on IFX or ADM therapy. Clinical remission and development of antibodies to anti-TNF drugs were not associated with TNF-α -238 and -308 polymorphisms., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Intestinal epithelial cell damage caused by SARS-CoV-2 infection was thought to be associated with gastrointestinal symptoms and decreased fecal consistency. The association of the gastrointestinal symptoms with the COVID-19-mediated inflammatory response triggered by the gastrointestinal immune system was investigated in this paper. Intestinal inflammation marker fecal calprotectin along with serum calprotectin and other inflammatory markers were measured in COVID-19 cases with and without GI manifestations as well as healthy individuals. Analyses were performed to compare COVID-19 patient subgroups and healthy controls and examine the relationship between fecal and serum calprotectin levels with gastrointestinal symptoms and disease severity. COVID-19 patients (n = 70) were found to have markedly elevated median levels of fecal (124.3 vs. 25.0 µg/g; P < 0/0001) and serum calprotectin (3500 vs. 1060 ng/mL; P < 0/0001) compared with uninfected controls. Fecal and serum calprotectin levels were not significantly different between COVID-19 patients who displayed GI symptoms and those who did not. Compared with other acute phase markers, both fecal and serum calprotectin were superior in identifying COVID-19 patients who progressed to severe illness. Although the progression of COVID-19 disease is marked by an elevation of fecal and serum calprotectin, gastrointestinal symptoms or diarrhea were not correlated with calprotectin increase level., (© 2021. The Author(s).)

Immune disorders play an important role in the pathogenesis of Crohn's disease (CD). Notably, the increased immune response of Th1 cells and related cytokines is associated with the onset of CD. IL-27 is a newly discovered IL-12-related cytokine, but its expression and clinical significance in CD patients are still controversial. This study is aimed at evaluating the serum levels of IL-27 in CD patients and analyzing their clinical significance. The results indicated that serum levels of IL-27 in CD patients were significantly higher than those in control subjects (median (interquartile range (IQR)): 110.0 (95.0, 145.0) vs. 85.0 (80.0, 95.0) pg/ml, P < 0.001). Furthermore, the IL-27 levels significantly increased in CD patients at the active stage compared with CD patients in remission (CDR) (127.5 (100.0, 150.0) vs. 90 (80.0, 110.0) pg/ml, P < 0.001). However, there was no difference in IL-27 levels between CDR and control subjects. The levels of IL-27 were positively correlated with Crohn's disease activity index (CDAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC), and Simple Endoscopic Score for Crohn's Disease (SES-CD) and negatively correlated with hemoglobin (Hb) and serum albumin (ALB). IL-27 combined with CRP favored the prediction of CD activity (area under the curve (AUC): 0.88). Additionally, the proportions of Th17 and Th1 cells in peripheral blood were higher in CD patients than in control subjects. Active CD patients exhibited significantly higher proportions of Th17 and Th1 cells than those in remission. Moreover, correlation analysis indicated that the serum levels of IL-27 were positively associated with the frequency of Th17 cells in CD patients ( r = 0.519, P = 0.013) but not associated with the frequency of Th1 cells in CD patients. IL-27 is positively associated with multiple inflammation indicators and may exert a proinflammatory profile by regulating Th17 cell differentiation in the development of Crohn's disease. In the future, IL-27 combined with CRP is expected to become an important biological marker of CD activity., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Xiufang Cui et al.)

Abstract: The aim of this study was to assess the appropriate time interval to identify the association between the fecal calprotectin (FC) test and endoscopic activity, and to evaluate whether the time interval affects the therapeutic plan adjustment in patients with ulcerative colitis (UC).This study included 103 patients who underwent FC tests and endoscopic examinations within the past three months. The FC test results classified cases into three groups as follows: moderate to severe (>200, >250, or >300 μg/g), mild (100-200, 100-250, or 100-300 μg/g), and inactive (<100 μg/g) activity. The Mayo endoscopic subscore was used to determine endoscopic activity. Therapeutic plan adjustment included the addition or increased dosage of anti-inflammatory drugs, steroids, immunomodulators, and biologics.Using the cutoff value for FC of 200 μg/g, the appropriate time interval for dividing the association and non-association between Mayo endoscopic subscore and FC was 7 days (sensitivity, 74.4%; specificity, 50.0%; area under the curve [AUC], 0.6032). When using FC 250 or 300 μg/g, the appropriate time interval was 5.5 days, with a sensitivity of 71.7% and specificity of 49.1 (AUC 0.5862) in FC 250 μg/g, a sensitivity of 69.6%, and a specificity of 47.4 (AUC 0.5549) for FC 300 μg/g. Therapeutic plans changed in 29.1% of patients. In patients with shorter intervals (≤7 days) between the FC test and endoscopy, significant therapeutic plan adjustments were observed in patients with UC (36.5% vs. 17.5%, P = .047).Although the need for endoscopy within 7 days after detecting high FC (≥ 200 μg/g) was not statistically supported, endoscopy within a shorter interval (≤7 days) in UC patients with high FC can help determine the therapeutic plan., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Fecal calprotectin (FC) is widely used for the diagnosis and monitoring disease activity of inflammatory bowel disease (IBD). Quantitative rapid assays can be a reliable alternative to the time-consuming assay. This study aimed to evaluate and compare the diagnostic performance of two quantitative rapid FC assays (Ichroma calprotectin, and Buhlmann Quantum blue)., Methods: A total of 192 patients were included in this study; 84 patients with IBD (67 ulcerative colitis and 17 Crohn's disease) and 108 patients with non-IBD. We compared quantitative FC levels in different disease statuses and evaluated the correlation between the FC results of the two FC kits. Diagnostic performances in predicting active IBD were evaluated in reference to different cut-off levels., Results: The FC levels in 45 patients with active IBD as defined by endoscopic score were significantly higher compared to the inactive IBD and other diseases (P<0.05). Although the two assays' results correlated (r = 0.642, P < 0.001), a significant deviation was observed (y (Buhlmannn) = -45.2 +8.9X (Ichroma)). The Diagnostic performances in predicting active IBD were comparable as area under the curve (AUC), 0.812, cut-off, 50, sensitivity, 64.4%, and specificity, 85.0% for iChroma assay and AUC, 0.826, cut-off, 100, sensitivity, 84.4%, and specificity 61.9% for Buhlmann Quantum Blue assay. FC levels using a cut-off of > 250 μg/g confirmed 85.7% (iChroma) and 64.1% (Buhlmann) of active IBD patients., Conclusion: The results of the two rapid FC assays iChroma and Buhlmann showed a significant correlation, but the two test results were not interchangeable. With optimized cut-off values, rapid FC tests could be helpful in the diagnosis of IBD and differentiating active IBD from inactive or organic bowel disease., Competing Interests: The authors have declared that no competing interests exist.

Background: Data suggests that tight objective monitoring may improve clinical outcomes in IBD., Aim: To assess the adherence to serial tight objective monitoring(clinical and biomarkers) and its effect on clinical outcomes., Methods: We retrospectively reviewed the chart of 428 consecutive IBD patients started on adalimumab between January 1,2015-January 1,2019 [338 Crohn's disease(CD), 90 ulcerative colitis(UC)]. Clinical symptoms(assessed by Harvey-Bradshaw-Index,partial Mayo),C-Reactive Protein(CRP), and fecal calprotectin(FCAL) assessments were captured at treatment initiation and at 3,6,9, and12 months. Dose optimization and drug sustainability curves were plotted by Kaplan-Meier method., Results: Clinical evaluation was available in nearly all patients at 3(CD-UC:95-94%), 6(90-83%), 9(86-85%) and 12(96-89%) months. CRP testing frequency decreased in CD patients over time. Compliance to serial FCAL testing was low. Clinical remission at one-year was higher in patients adherent to early assessment visit at 3 months(p = 0.001 for CD and UC). Adherence to early follow-up resulted in earlier dose optimization in CD and UC patients(pLogrank=0.026 for UC & p = 0.09 for CD). Overall drug sustainability did not differ., Conclusion: Clinical & CRP, but not FCAL, were frequently assessed in patients starting adalimumab. Adherence to early objective combined follow-up visits resulted in earlier dose optimization, improved one-year clinical outcomes but did not change drug sustainability., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Siblings of people with Crohn's disease (CD) share aspects of the disease phenotype (raised faecal calprotectin, altered microbiota), which are markers of risk for their own development of CD. The aim was to determine whether supplementation with prebiotic oligofructose/inulin induces a prebiotic response and impacts the risk phenotype in CD patients and siblings., Methods: Patients with inactive CD (n = 19, CD activity index <150) and 12 of their unaffected siblings (with calprotectin >50 μg/g) ingested oligofructose/inulin (15 g/day) for three weeks. Faecal microbiota (qPCR), intestinal permeability (lactulose-rhamnose test), blood T cells (flow-cytometry) and calprotectin (ELISA) were measured at baseline and follow-up., Results: Following oligofructose/inulin, calprotectin did not significantly change in patients (baseline mean 537 SD 535 μg/g; follow-up mean 974 SD 1318 μg/g, p = 0.08) or siblings (baseline mean 73 SD 90 μg/g: follow up mean 58 SD 72 μg/g, p = 0.62). Faecal Bifidobacteria and Bifidobacterium longum increased in patients and siblings; Bifidobacterium adolescentis and Roseburia spp. increased only in siblings. Compared with patients, siblings had a greater magnitude change in Bifidobacteria (+14.6% vs +0.4%, p = 0.028), B. adolescentis (+1.1% vs 0.0% p = 0.006) and Roseburia spp. (+1.5% vs -0.1% p = 0.004). Intestinal permeability decreased significantly in patients after oligofructose/inulin to a level that was similar to siblings. Blood T cell abundance reduced in siblings but not patients following oligofructose/inulin., Conclusions: Oligofructose/inulin supplementation did not significantly impact calprotectin, but the prebiotic effect was more marked in healthy siblings compared with patients with inactive CD and was associated with alterations in other CD risk markers. Future research should focus on dietary intervention, including with prebiotics, in the primary prevention of CD., Competing Interests: Conflict of interest None of the authors had any financial or personal relationships with the company or organization sponsoring the research at the time the research was done. CRH has received speaker fees from Takeda, Ferring, AbbVie, and Janssen, and consultancy fees from Pfizer. She has acted as local principal investigator for clinical trials for Janssen and GlaxoSmithKline. SM, AJS & JOL have nothing to disclose; NEM reports grants and personal fees from ImCheck Therapeutics SAS, outside the submitted work; PL & FMF reports grants from Scottish Government Rural and Environment Science and Analytical Services, during the conduct of the study; KW reports grants from Core (Guts UK), during the conduct of the study; grants from Clasado Biosciences, Danone, International Nut and Dried Fruit Board, Almond Board of California, outside the submitted work; In addition, KW has a patent FODMAP by FoodMaestro with royalties paid to King's College London, Guys and St Thomas NHS Foundation Trust and FoodMaestro, and a patent for Volatile Organic Compounds as markers of response to diet in IBS with royalties paid to King's College London and University of Liverpool., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Introduction: Cost-effectiveness of biomarker- vs endoscopy-based treat-to-target monitoring in Crohn's disease (CD) is unknown., Methods: A microsimulation model for CD was built to simulate biomarker (fecal calprotectin) vs endoscopy-based monitoring in a treat-to-target fashion. Published literature in combination with patient-level data from phase 3 clinical trials and population estimates for therapeutic drug monitoring were used to generate transition probabilities, costs, and utilities. Tracker variables were used to modify downstream probabilities and outcomes based on previous exposures, response patterns, and disease-related complications or surgery history. The primary outcome was cost-effectiveness over a 5-year horizon at a willingness-to-pay threshold of $100,000/quality-adjusted life-year. Probabilistic sensitivity analyses in addition to multiple 1-, 2-, and 3-way microsimulation sensitivity analyses were performed., Results: In the base-case model, the endoscopy-based monitoring strategy dominated the biomarker-based monitoring strategy over a 5-year horizon. Over shorter periods of observation, the biomarker-based monitoring strategy became progressively more cost-effective, with cost-effectiveness achieved for this strategy over a 1-year horizon. Therapeutic drug monitoring did not influence short-term cost-effectiveness of biomarker-based monitoring. Once in endoscopic remission, continued biomarker-based vs endoscopy-based monitoring was more cost-effective. A hybrid biomarker-endoscopy-based monitoring strategy dominated the endoscopy-based monitoring strategy over a 5-year horizon. The strongest determinants for cost-effectiveness were cost of colonoscopy and diagnostic performance of fecal calprotectin., Discussion: The most cost-effective approach for treat-to-target monitoring in CD is up-front biomarker-based monitoring followed by endoscopy-based monitoring if not in endoscopic remission by 1 year and then returning to biomarker-based monitoring once in endoscopic remission., (Copyright © 2021 by The American College of Gastroenterology.)

Gastrointestinal dysbiosis is common among persons with type 1 diabetes (T1D), but its potential impact on diabetic nephropathy (DN) remains obscure. We examined whether faecal biomarkers, previously associated with low-grade gastrointestinal inflammation, differ between healthy controls and T1D subjects with and without DN. Faecal samples were analyzed for levels of calprotectin, intestinal alkaline phosphatase (IAP), short-chain fatty acids (SCFA) and immunoglobulins in subjects with T1D (n = 159) and healthy controls (NDC; n = 50). The subjects with T1D were stratified based on albuminuria: normoalbuminuria (< 30 mg/g; n = 49), microalbuminuria (30-299 mg/g; n = 50) and macroalbuminuria (≥ 300 mg/g; n = 60). aecal calprotectin, IAP and immunoglobulin levels did not differ between the T1D albuminuria groups. However, when subjects were stratified based on faecal calprotectin cut-off level (50 µg/g), macroalbuminuric T1D subjects exceeded the threshold more frequently than NDC (p = 0.02). Concentrations of faecal propionate and butyrate were lower in T1D subjects compared with NDC (p = 0.04 and p = 0.03, respectively). Among T1D subjects, levels of branched SCFA (BCFA) correlated positively with current albuminuria level (isobutyrate, p = 0.03; isovalerate, p = 0.005). In our study cohort, fatty acid metabolism seemed to be altered among T1D subjects and those with albuminuria compared to NDC. This may reflect gastrointestinal imbalances associated with T1D and renal complications., (© 2021. The Author(s).)

Background: Fecal S100/calgranulin (S100A12 and calprotectin) concentrations are useful markers of gastrointestinal inflammation in dogs. In people, fecal S100/calgranulin concentrations are affected by age, obesity, diet and other lifestyle factors. Knowledge about the effects of such factors on fecal S100/calgranulin concentrations in dogs is currently scarce., Objective: To evaluate the association between several factors and fecal S100/calgranulin concentrations in a large cohort of healthy adult dogs., Methods: Single-spot fecal samples from 181 healthy pet dogs and data derived from a standard questionnaire served to evaluate the effect of age, sex, reproductive status, body weight and body condition, breed type and size, vaccination, endoparasite treatment, diet, environment and travel history on fecal S100/calgranulin concentrations and the fecal calgranulin ratio (fCalR)., Results: Univariate analysis showed a significant association of reproductive status (in female dogs) and breed size with fecal S100A12, fecal calprotectin and fCalR. Breed type was linked to fecal S100A12 concentrations and fCalR; recent vaccination (particularly with a vaccine against canine parvovirus) to fCalR. In multivariate models, breed size was linked to fecal S100A12 and calprotectin concentrations, and recent vaccination affected S100A12 concentrations., Conclusions: Breed size, recent vaccination and reproductive status in female dogs can affect fecal S100/calgranulin concentrations, and these biomarkers should be interpreted in light of those confounding factors. The utility of reference intervals for fecal canine S100/calgranulin concentrations might be improved through stratification by sex/reproductive status and breed size. Fecal canine S100/calgranulin concentrations are not confounded by age, body condition, deworming, diet, environment or travel history., (© 2021 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

In the search for improved stool biomarkers for inflammatory bowel disease (IBD), an aptamer-based screen of 1129 stool proteins was conducted using stool samples from an IBD cohort. Here we report that of the 20 proteins subsequently validated by ELISA, stool Ferritin, Fibrinogen, Haptoglobin, Hemoglobin, Lipocalin-2, MMP-12, MMP-9, Myeloperoxidase, PGRP-S, Properdin, Resistin, Serpin A4, and TIMP-1 are significantly elevated in both ulcerative colitis (UC) and Crohn's disease (CD) compared to controls. When tested in a longitudinal cohort of 50 UC patients at 4 time-points, fecal Fibrinogen, MMP-8, PGRP-S, and TIMP-2 show the strongest positive correlation with concurrent PUCAI and PGA scores and are superior to fecal calprotectin. Unlike fecal calprotectin, baseline stool Fibrinogen, MMP-12, PGRP-S, TIMP-1, and TIMP-2 can predict clinical remission at Week-4. Here we show that stool proteins identified using the comprehensive aptamer-based screen are superior to fecal calprotectin alone in disease monitoring and prediction in IBD.

Background and Aims: Ontamalimab, a fully-human monoclonal antibody targeting MAdCAM-1, induced remission in patients with moderate-to-severe ulcerative colitis [UC] in the TURANDOT study. We aimed to assess long-term safety, tolerability, and efficacy of ontamalimab in TURANDOT II., Methods: TURANDOT II was a phase 2, multicentre, open-label [OL] study in patients with moderate-to-severe UC who completed TURANDOT on placebo or ontamalimab (NCT01771809). Patients were randomised to 75 mg or 225 mg ontamalimab every 4 weeks for 72 weeks [OL1]. The dosage could be increased to 225 mg from Week 8 at the investigator's discretion. All patients then received 75 mg every 4 weeks for 72 weeks [OL2], followed by 6-month safety follow-up. The primary objective was safety, measured by adverse events [AEs], serious AEs [SAEs], and AEs leading to withdrawal. Mucosal healing [MH; centrally read endoscopy] was assessed., Results: Of 330 patients, 180 completed OL1; 94 escalated to 225 mg; 127 completed OL2. Overall, 36.1% experienced drug-related AEs. The most common SAE [10.0%] was worsening/ongoing UC; 5.5% of patients had serious infections, the most common being gastroenteritis [0.9%]. One death and four cancers [all unrelated to ontamalimab] occurred. No PML [progressive multifocal leukoencephalopathy]/lymphoproliferative disorders occurred. Geometric mean high-sensitivity C-reactive protein [hsCRP] and faecal calprotectin decreased across OL1 in both dose groups. The proportion of patients assigned to placebo in TURANDOT achieving MH increased from 8.8% [6/68] at baseline to 35.3% at Week 16 [24/68; non-responder imputation]. The corresponding increase in the ontamalimab group was from 23.3% [61/262] to 26.7% [70/262]., Conclusions: Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: As the reliability of fecal calprotectin (Fcal) remains debatable to detect endoscopic ulcerations in patients with pure ileal Crohn's disease (CD), we aimed to compare its performances with those observed in patients with colonic or ileocolonic location., Methods: Using a prospectively maintained database, we analyzed 123 CD patients with Fcal measurement and ileocolonoscopy performed within 1 month with no therapeutic intervention during this interval. Receiver operating characterstic curves (ROC) were used to determine the best Fcal threshold to detect endoscopic ulcerations, taking into account the clinical relevance and usual recommended indices. Sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) were presented with 95% confidence intervals., Results: The mean Fcal level was significantly higher in patients with endoscopic ulcerations in the L1 group (P = 0.025) and the L2-L3 group (P < 0.001). Using ROC curves, Fcal >200 µg/g and Fcal >250 µg/g were the best thresholds to detect endoscopic ulcerations in the L1 group (sensitivity = 75.0, 95% CI, 47.6-92.7; specificity = 87.5, 95% CI, 67.6-97.3; PPV = 80.0, 95% CI, 51.9-95.7; and NPV = 84.0; 95% CI, 63.9-95.5) and in the L2-L3 group (sensitivity = 84.1 95% CI, 69.9-93.4; specificity = 74.4, 95% CI, 57.9-87.0; PPV = 78.7, 95% CI, 64.3-89.3, and NPV = 80.6, 95% CI, 64.0-91.8), respectively. We compared the AUC between L1 and L2-L3 groups, and no difference was shown (0.89 vs 0.84, respectively, P = 0.46). We also compared 2-by-2 sensitivity, specificity, PPV, NPV, and accuracy and we did not observe any significant difference., Conclusion: Fecal calprotectin is highly effective to detect endoscopic ulcerations regardless of CD location but requires a lower cutoff value in patients with pure ileal involvement., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: One third of coronavirus disease 2019 (COVID-19) patients have gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA has been detected in stool samples of approximately 50% of COVID-19 individuals. Fecal calprotectin is a marker of gastrointestinal inflammation in the general population., Aim: To investigate if fecal calprotectin correlates with SARS-CoV-2 intestinal shedding in COVID-19 patients with pneumonia., Methods: Patients with SARS-CoV-2 pneumonia admitted to the Infectious Disease Unit (University Hospital of Trieste, Italy) from September to November 2020 were consecutively enrolled in the study. Fecal samples were collected and analyzed for quantification of fecal calprotectin (normal value < 50 mg/kg) and SARS-CoV-2 RNA presence by polymerase chain reaction (PCR). Inter-group differences were determined between patients with and without diarrhea and patients with and without detection of fecal SARS-CoV-2., Results: We enrolled 51 adults (40 males) with SARS-CoV-2 pneumonia. Ten patients (20%) presented with diarrhea. Real-time-PCR of SARS-CoV-2 in stools was positive in 39 patients (76%), in all patients with diarrhea (100%) and in more than two thirds (29/41, 71%) of patients without diarrhea. Obesity was one of the most common comorbidities (13 patients, 25%); all obese patients (100%) ( P = 0.021) tested positive for fecal SARS-CoV-2. Median fecal calprotectin levels were 60 mg/kg [interquartile range (IQR) 21; 108]; higher fecal calprotectin levels were found in the group with SARS-CoV-2 in stools (74 mg/kg, IQR 29; 132.5) compared to the group without SARS-CoV-2 (39 mg/kg, IQR 14; 71) ( P < 0.001)., Conclusion: High fecal calprotectin levels among COVID-19 patients correlate with SARS-CoV-2 detection in stools supporting the hypothesis that this virus can lead to bowel inflammation and potentially to the 'leaky gut' syndrome., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

We evaluated the association between endoscopic scores of colonic inflammation and fecal calprotectin (FC), fecal immunochemical occult blood test (FIT), and C-reactive protein (CRP) in patients with ulcerative colitis (UC). Endoscopic scores reflecting the most severe lesion [maximum Mayo Endoscopic Subscore (M-MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS)] and those reflecting the inflammation of the entire colon [sum of MES (S-MES) and Ulcerative Colitis Colonoscopic Index of Severity (UCCIS)] were evaluated. FC, FIT, and CRP were measured, and their association with the four endoscopic scores was evaluated. Endoscopic scores of 78 complete colonoscopies (66 UC patients) were evaluated using the three biomarkers. FC and CRP tended to correlate more strongly with S-MES and UCCIS than with M-MES and UCEIS. In the M-MES 0, 1 group, compared to CRP, FC and FIT showed stronger correlations with S-MES and UCCIS. Conversely, in the M-MES 2, 3 group, only CRP was significantly correlated with each descriptor. CRP more strongly reflects colon-wide mucosal inflammation than FC and allows reliable assessment of inflammation throughout the colon in active UC.

In previous studies, measuring the levels of calprotectin in patients with pleural effusion (PE) was an exceptionally accurate way to predict malignancy. Here, we evaluated a rapid method for the measurement of calprotectin levels as a useful parameter in the diagnosis of malignant pleural effusion (MPE) in order to minimise invasive diagnostic tests. Calprotectin levels were measured with Quantum Blue® sCAL (QB®sCAL) and compared with the gold standard reference ELISA method. Calprotectin levels in patients with benign pleural effusion (BPE) were significantly higher (p < 0.0001) than for MPE patients. We measured the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios (LRs) for a cut-off value of ≤ 14,150 ng/mL; the diagnostic accuracy was 64%. The odds ratio for PE calprotectin levels was 10.938 (95% CI [4.133 - 28.947]). The diagnostic performance of calprotectin concentration was better for predicting MPE compared to other individual parameters. Comparison of two assays showed a slope of 1.084, an intercept of 329.7, and a Pearson correlation coefficient of 0.798. The Bland-Altman test showed a positive bias for the QB®sCAL method compared to ELISA fCAL®. Clinical concordance between both these methods was 88.5% with a Cohen kappa index of 0.76 (95% CI [0.68 - 0.84]). We concluded that QB®sCAL is a fast, reliable, and non-invasive diagnostic tool for diagnosing MPE and represents an alternative to ELISA that could be implemented in medical emergencies., Competing Interests: No authors have competing interests

Background: Despite several synovial fluid biomarkers for the diagnosis of periprosthetic joint infection (PJI) having been investigated, point-of-care (POC) tests using these biomarkers are not widely available. Synovial calprotectin has recently been reported to effectively exclude the diagnosis of PJI. Thus, the objective of this study was to test the value of a calprotectin POC test for PJI diagnosis in patients undergoing total knee arthroplasty (TKA) using the 2013 Musculoskeletal Infection Society (MSIS) PJI diagnosis criteria as the gold standard., Methods: Synovial fluid samples were prospectively collected from 123 patients who underwent revision TKA at 2 institutions within the same health-care system from October 2018 to January 2020. The study was conducted under institutional review board approval. Data collection comprised demographic, clinical, and laboratory data in compliance with the MSIS criteria. Synovial fluid samples were analyzed by calprotectin POC tests in accordance with the manufacturer's instructions. Revisions were categorized as septic or aseptic using MSIS criteria by 2 independent reviewers blinded to the calprotectin results. Calprotectin test performance characteristics with sensitivities, specificities, positive predictive values, negative predictive values, and areas under the receiver operating characteristic curve (AUC) were calculated for 2 different PJI diagnosis scenarios: (1) a threshold of ≥50 mg/L, and (2) a threshold of ≥14 mg/L., Results: According to the MSIS criteria, 53 revision TKAs were septic and 70 revision TKAs were aseptic. In the ≥50-mg/mL threshold scenario, the calprotectin POC performance showed a sensitivity of 98.1%, a specificity of 95.7%, a positive predictive value of 94.5%, a negative predictive value of 98.5%, and an AUC of 0.969. In the ≥14-mg/mL threshold scenario, the sensitivity was 98.1%, the specificity was 87.1%, the positive predictive value was 85.2%, the negative predictive value was 98.4%, and the AUC was 0.926., Conclusions: The calprotectin POC test has excellent PJI diagnostic characteristics, including high sensitivity and specificity in patients undergoing revision TKA. This test could be effectively implemented as a rule-out test. However, further investigations with larger cohorts are necessary to validate these results., Level of Evidence: Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: This study was funded by Lyfstone (Tromso, Norway). On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work and “yes” to indicate that the author had other relationships or activities that could be perceived to influence, or have the potential to influence, what was written in this work (http://links.lww.com/JBJS/G446)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

To date, data on effectiveness and safety of Adalimumab (ADA) biosimilars in inflammatory bowel diseases (IBDs) are lacking. Therefore, we aimed to verify the ability of ABP501 and SB5 to maintain the clinical and biochemical response induced by the ADA originator, after switching to them. We prospectively analyzed data collected from 55 patients with IBD who switched to ABP501, and 25 patients with IBD who switched to SB5, from ADA originator at four IBD Units between 2018 and 2020. In addition, we included an age and sex-matched control group (n = 38) who continued ADA originator for at least two years and who did not switch to a biosimilar drug. Clinical and biochemical data (C-Reactive Protein (CRP), fecal calprotectin (FC)), concomitant steroid and/or immunosuppressant therapy at the time of the switch and after six months were collected. At six months, in the ABP501 group, we did not observe statistically significant modifications in clinical activity of disease (p = 0.09) and FC values (p = 0.90) . Some patients (n = 8) needed to add steroids at six months after switching (p = 0.01), however the need for optimization was not significant between the two timepoints (p = 0.70). Finally, 14.5% patients stopped therapy after six months. Similarly, in the SB5 group we observed a stability of clinical activity and FC values (p = 0.90 and p = 0.20), and a concomitant statistically significant decrease in CRP (p = 0.03). There were no differences in steroids/immunosuppressants need or optimizing biological therapy in this group. Finally, drug survival curves of patients who switched from originator to ABP501 and those who continued ADA originator were similar (p = 0.20). Overall, biosimilar drugs seem to be as effective and safe as the originator. Further larger and longer studies are mandatory to understand the clinical implications of these findings.

Fatigue is common in all chronic inflammatory and autoimmune diseases. A conceptual model for understanding the biological basis of fatigue describes it as being a part of the sickness behaviour response generated by pro-inflammatory cytokines and other mediators. We hypothesised that the pro-inflammatory high mobility group box 1 (HMGB1) protein is a fatigue-inducing molecule and that auto-Abs against HMGB1 reduce fatigue. We measured Abs against disulphide (ds) HMGB1 and fully reduced (fr) HMGB1 in plasma from 57 patients with Crohn's disease. Fatigue was rated using the fatigue visual analogue scale (fVAS) and disease activity with faecal calprotectin, C-reactive protein and the Simple Endoscopic Score for Crohn's disease. Multivariable regression models identified anti-dsHMGB1 and anti-frHMGB1 Abs as the strongest contributing factors for fVAS scores ( B  = -29.10 ( P  = 0.01), R 2  = 0.17, and B  = -17.77 ( P  = 0.01), R 2  = 0.17, respectively). Results indicate that anti-HMGB1 auto-Abs alleviate fatigue possibly by down-regulating HMGB1-induced sickness behaviour.

Objectives: Following the disruption of normal paediatric inflammatory bowel disease (IBD) services during the peak of the COVID-19 pandemic, we prospectively audited the first-time use of home faecal calprotectin testing. We aimed to provide an alternative to laboratory tests and to assess the value of home testing as part of our regular services going forward., Methods: Home test kits as well as accompanying user instructions were made available to our patients with paediatric IBD that required faecal calprotectin test between 17 April and 12 August 2020. Once the user completed the test, results were automatically uploaded to the result portal and clinical staff were alerted. A user feedback questionnaire was sent to users that had completed the home test., Results: Of the 54 patients, 41 (76%) aged between 4.7 and 18.1 years used the home test. A total of 45 home tests were done, one of which produced an invalid result. The decision to modify management was made in 12 (29%) of the patients, while 14 (34%) had no changes made and 15 (37%) required further assessment. Twenty (48.8%) responded to the questionnaire and 85% stated that they preferred the home test to the laboratory testing method., Conclusions: Home calprotectin tests were useful in guiding clinical management during a time when laboratory testing was less available. They may offer benefits as part of routine paediatric IBD monitoring to help target appointments and reduce unnecessary hospital attendances in the future., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Faecal calprotectin has been widely used as a non-invasive marker of intestinal inflammation in children. Measurement of faecal haemoglobin using faecal immunochemical test is well established in adults for detection of colorectal cancer. In adults, faecal haemoglobin has been recommended as a reliable tool to aid identification of those at low risk of significant bowel disease and has also been used in inflammatory bowel disease to assess mucosal healing., Aims: We aimed to evaluate the performance of faecal haemoglobin in the paediatric population and compare it with faecal calprotectin., Methods: Children being assessed in the paediatric gastroenterology clinic for bowel symptoms had a sample sent for both faecal calprotectin and faecal haemoglobin. Samples were collected over a 10-month period from November 2018 to September 2019. Faecal haemoglobin was measured using an OC-Sensor. Faecal calprotectin was measured using Liason®Calprotectin., Results: One hundred forty three samples were returned for faecal haemoglobin and in 107 a paired faecal calprotectin was also available. Faecal haemoglobin correlated with faecal calprotectin, Spearman's rank coefficient 0.656 ( P  < 0.0001). There were 35 patients with faecal haemoglobin >20 μg/g and in 32 of these patients faecal calprotectin was >200 μg/g; 74 patients with faecal haemoglobin and 38 patients with faecal calprotectin underwent colonoscopy. Patients with normal histology had faecal haemoglobin <4 μg/g; faecal haemoglobin >20 µg/g was associated with signification inflammation., Conclusion: Our study is the first to compare faecal haemoglobin and faecal calprotectin in a paediatric population. Results suggest that faecal haemoglobin correlates with faecal calprotectin and, as in adults, may be useful to rule out significant bowel disease. A faecal haemoglobin >20 μg/g was consistent with significant histological inflammation.

Introduction: The aim of this study was to provide an external validation of bowel ultrasound (US) predictors of activity in ulcerative colitis (UC) and quantitative Milan Ultrasound Criteria (MUC)., Methods: Forty-three consecutive patients with UC (16 in endoscopic remission and 27 with endoscopic activity) underwent bowel US and colonoscopy in a tertiary referral inflammatory bowel disease unit., Results: An MUC score >6.2 discriminated patients with active versus non-active UC with a sensitivity of 0.85 (95% confidence interval (CI) 0.66-0.96), specificity of 0.94 (95% CI 0.70-0.99) and an area under the curve of 0.902 (95% CI 0.772-0.971) in complete agreement with the derivation study., Conclusion: The external validation of MUC confirms that it is an accurate tool for assessing disease activity in patients with UC., (© 2020 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Background: Intestinal and hepatic manifestations of lupus seem to be underestimated in comparison to other major organ lesions. Although recent data point to gut-liver axis involvement in lupus, gut permeability dysfunction and liver inflammation need to be more investigated., Objective: This study aims to assess fecal calprotectin, intestinal tight junction proteins and liver inflammation pathway in wild-type murine imiquimod- induced lupus., Methods: C57BL/6 mice were topically treated on their right ears with 1.25 mg of 5% imiquimod cream, three times per week for six weeks. Fecal calprotectin was collected at day 0, 22 and 45. Renal, liver and intestinal pathology, as well as inflammatory markers, intestinal tight junction proteins, and E. coli protein in liver were assessed at sacrifice., Results: At six weeks, lupus nephritis was confirmed on histopathology and NGAL and KIM-1 expression. Calprotectin rise started at day 22 and persists at day 45. Protein expression of Claudine, ZO-1 and occludin was significantly decreased. E. coli protein was significantly increased in liver with necro-inflammation and increased TLR4, TLR7, and pNFκB/NFκB liver expression., Conclusion: This study is the first to demonstrate early fecal calprotectin increase and liver activation of TLR4- NFκB pathway in wild-type murine imiquimod-induced lupus.

Background: The role of fecal calprotectin in predicting pregnancy-related outcomes in inflammatory bowel disease (IBD) remains unknown., Aim: To determine whether increased fecal calprotectin during pregnancy is associated with adverse pregnancy outcomes in IBD., Methods: This is a multicenter cohort study of women with IBD who underwent fecal calprotectin monitoring during pregnancy. Fecal calprotectin levels were stratified by trimester, and adverse pregnancy-related outcomes were recorded. The Mann-Whitney U test assessed differences between continuous variables, whereas categorical variables were compared using the Chi-squared test., Results: Eighty-five women with IBD were included. First trimester fecal calprotectin was higher in patients who underwent emergency Cesarean birth compared to those who had a vaginal delivery (503 ug/g, IQR 1554.3 ug/g vs. 130 ug/g, IQR 482 ug/g, p = .030, respectively) and in those who delivered infants with low birth weight compared to normal birth weight (1511 ug/g, IQR 579 ug/g vs. 168 ug/g, IQR 413 ug/g, p = .049, respectively). Third trimester fecal calprotectin was higher in those with non-elective induction of labor (334.5 ug/g, IQR 1411.0 ug/g) compared to those with spontaneous delivery (116.5 ug/g, IQR 227.1 ug/g) (p = .025). Those with a fecal calprotectin ≥ 250 ug/g in the second trimester had an increased incidence of infants with low birth weight (35.3% vs. 3.8%) (p = .049), whereas those with a fecal calprotectin ≥ 250 ug/g in the third trimester had an increased incidence of non-elective induction of labor (43.8% vs. 10.3%, p = .030)., Conclusions: Fecal calprotectin may be a useful noninvasive marker to predict adverse pregnancy-related outcomes in patients with IBD.

Background: Fecal calprotectin (FC) is a non-invasive marker of gut inflammation which is frequently used to guide therapeutic decisions in patients with inflammatory bowel diseases (IBD). Each step of FC measurement can influence the results, leading to misinterpretations and potentially impacting the management of IBD patients. To date, there is high heterogeneity between FC measurements and no current method is universally accepted as a standard., Aims: Our aim was to provide clear position statementsabout the pre-analytical and the analytical phases of FC measurement to homogenize FC levels and to minimize variability and risk of misinterpretation through aninternational consensus., Materials & Methods: Fourteen physicians with expertise in the field of IBD and FC from 11 countries attended a virtual international consensus meeting on July 17th, 2020. A systematic literature was conducted and the literature evidence was shared and discussedamong the participants. Statements were formulated, discussed, and voted. Statements were considered approved if all participants agreed., Results: Nine statements were formulated and approved. Based on the available evidence, quantitative tests should be preferred for measuring FC. Furthermore, FC measurement, if possible, should always be performed with the same method and factors influencing FC levels should be taken into account when interpreting the results., Discussion: FC has an increasingly important role in the management of patients with IBD. However, large multicenter studies should be conducted to define the reproducibility and to confirm the diagnostic accuracy of the available FC tests., Conclusion: FC concentrations guide clinicians' treatment decisions. Our statements have a relevant impact in daily practice and could be applied in clinical trials to standardize FC measurement., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Background: Fecal calprotectin (FC) is a common surrogate marker of mucosal healing (MH) in patients with ulcerative colitis (UC) and Crohn's disease (CD). We investigated the optimum FC thresholds for defining endoscopic remission (ER) and histological remission (HR) using advanced endoscopic techniques., Patients and Methods: In this cross-sectional study, we collected clinical, endoscopic, histological data, and FC from 76 UC and 41 CD patients. Receiver operating characteristic curves were created to evaluate the optimum cut-off of FC to predict ER evaluated by Mayo Endoscopic Score (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and modified PICaSSO (Paddington International Virtual Chromoendoscopy Score) for UC patients and Simple Endoscopic Score (SES-CD) in CD patients; and HR was scored by the Robarts Histology Index (RHI) and Nancy Index for UC and modified Riley for CD., Results: In UC patients, the best thresholds of FC to identify ER calculated with MES, UCEIS, and modified PICaSSO were 112, 148, and 161 mcg/g with accuracy of 86.9% 86.8%, and 81.6%, respectively. The best value of FC to predict HR was 112 mcg/g and 172 mcg/g with accuracy of 84.2% and 81.6% for RHI and Nancy Index, respectively.In CD patients, the best cut-off of FC to predict ER was 96 mcg/g with accuracy of 82.9%. The HR was best predicted by an FC value of 225 mcg/g with accuracy of 75.6%., Conclusions: The FC value threshold between 112 and 172 mcg/g could identify ER and HR in UC patients, whereas a value under 225 mcg/g should be considered for CD patients., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)