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Background: Calprotectin, a damage-associated molecular pattern protein of the S100/calgranulin family, is a potential marker of gastrointestinal inflammation in dogs and mainly originates from activated macrophages and granulocytes. Increased calprotectin concentrations are reported in feces and serum samples from dogs with chronic inflammatory enteropathy (CIE), but mucosal calprotectin expression has not been extensively investigated in canine CIE. Thus, we aimed to evaluate gastrointestinal mucosal concentrations of calprotectin in 62 dogs (44 dogs with CIE compared to 18 healthy Beagles) using a particle-enhanced turbidimetric immunoassay method. Additionally, we assessed the relationship of gastric, duodenal, jejunal, ileal, and colonic mucosal calprotectin levels with the clinical disease severity (canine clinical inflammatory bowel disease activity index, CIBDAI), histopathologic findings, clinical outcome, and serum albumin concentrations to further evaluate the potential of calprotectin as a biomarker for CIE., Results: Mucosal calprotectin concentrations in dogs with CIE were significantly higher in the duodenum (median: 276.2 μg/g) and colon (median: 298.2 μg/g) compared to healthy controls (median: 94.3 μg/g, P = 0.0039; and median: 112.0 μg/g, P = 0.0061). Similar numerical differences in the ileum and cecum were not statistically significant, and mucosal calprotectin concentrations correlated significantly among the different gastrointestinal segments. Histologic lesion severity was linked to mucosal calprotectin concentrations for inflammatory and structural histology criteria in the duodenum and colon (all P < 0.05). Higher mucosal calprotectin levels in the duodenum and across all segments correlated with lower serum albumin concentrations (both P < 0.05); duodenal mucosal calprotectin concentrations were more than sixfold higher in hypoalbuminemic dogs (median: 1441 µg/g, n = 4) than normoalbuminemic dogs (median: 227 µg/g, n = 40). There was no significant association of mucosal calprotectin levels with CIBDAI scores or individual clinical outcomes., Conclusions: These results show that duodenal and colonic mucosal calprotectin concentrations are increased in dogs with CIE, providing further supporting evidence for the diagnostic potential of fecal calprotectin (presumably reflecting mucosal) concentrations and in dogs with CIE. Further longitudinal research is needed to assess changes in mucosal calprotectin concentrations with clinical response to treatment vs. mucosal disease remission and to determine the clinical utility of fecal calprotectin concentrations to diagnose and monitor dogs with CIE in clinical practice., (© 2024. The Author(s).)

Background: Since diet is generally recognized as an important factor directly modulating the gut microbiome, it is also considered a potential environmental triggering factor for the pathogenesis and onset of inflammatory bowel disease (IBD). While the habitual and sex-related dietary behavior of the general population has been the subject of extensive study and reporting, data on IBD patients' dietary behavior and especially its sex-related differences are underrepresented. However, as diet is an important factor in the course of IBD, we hypothesized that men and women with IBD have a different dietary profile than the general population., Methods: We performed a cohort analysis of a monocentric, cross-sectional study and compared the sex-related dietary behavior of 82 IBD patients ( n = 40 women) to a sex- and age-matched cohort of the general German population [ n = 328 ( n = 160 women)]. Further on, disease-related quality of life and fecal calprotectin were correlated to the IBD patients' dietary behavior., Results: While sex-related dietary behavior was frequently of statistical difference in the general population within the IBD cohort, only minor numerical differences were observed between the sexes, which were rarely statistically significant. However, correlation analyses of disease-related quality of life (IBDQ) and diet revealed significant differences in male IBD patients but not in female IBD patients ( p = 0.007; r = 0.409 for energy intake (kJ/d); p = 0.003, r = 0.449 for adherence to Mediterranean diet)., Conclusion: The dietary behavior of IBD patients showed more similarity between the sexes than the general German population. Distinct sex-related trends and differences in correlation with disease parameters demonstrated a significant difference for an adaptive dietary behavior, especially in IBD men.

Objective: The aim of our study was to investigate whether a 1-month-long milk-free diet results in a reduction in faecal calprotectin (FC) and faecal-zonulin-related proteins (FZRP) in children with milk-protein-induced allergic proctocolitis (MPIAP)., Materials and Methods: This is a single-centre, prospective, observational cohort study involving 86 infants with MPIAP, aged 1-3 months, and 30 healthy controls of the same age. The FC and FZRP were marked using the ELISA method (IDK ® Calprotectin or Zonulin ELISA Kit, Immunodiagnostik AG, Bensheim, Germany). The diagnosis of MPIAP was confirmed with an open milk challenge test., Results: FFC and FZRP proved useful in evaluating MPIAP treatment with a milk-free diet, and the resolution of allergic symptoms and a significant ( p = 0.0000) decrease in the concentrations of both biomarkers were observed after 4 weeks on the diet. The FC and FZRP concentrations were still higher than in the control group. A high variability of FC concentrations was found in all the study groups. An important limitation is the phenomenon of FZRP not being produced in all individuals, affecting one in five infants., Conclusions: FC and FZRP can be used to monitor the resolution of colitis in infants with MPIAP treated with a milk-free diet, indicating a slower resolution of allergic inflammation than of allergic symptoms. The diagnosis of MPIAP on the basis of FC concentrations is subject to considerable error, due to the high individual variability of this indicator. FZRP is a better parameter, but this needs further research, as these are the first determinations in infants with MPIAP.

Parkinson's disease is associated with gastrointestinal (GI) dysfunction, including constipation symptoms and abnormal intestinal permeability and inflammation. A Mediterranean diet (MediDiet) may aid in disease management . This parallel, randomized, controlled trial in people with Parkinson's (PwP) and constipation symptoms compared a MediDiet against standard of care on change in constipation symptoms, dietary intake, and fecal zonulin and calprotectin concentrations as markers of intestinal permeability and inflammation, respectively. Participants were randomized to either standard of care for constipation (control; n = 17, 65.1 ± 2.2 years) or a MediDiet plus standard of care ( n = 19, 68.8 ± 1.4 years) for 8 weeks. Constipation scores decreased with both interventions ( p < 0.01), but changes from baseline were not different between groups (MediDiet, -0.5 [-1.0, 0]; control, -0.8 [-1.0, 0.2]; median [25th, 75th]; p = 0.60). The MediDiet group had a higher intake of dietary fiber at week 4 than the control group (13.1 ± 0.7 g/1000 kcal vs. 9.8 ± 0.7 g/1000 kcal; p < 0.001). No differences in fecal zonulin were observed between groups ( p = 0.33); however, fecal calprotectin tended to be lower in the MediDiet group at week 8 (45.8 ± 15.1 µg/g vs. 93.9 ± 26.8 µg/g; p = 0.05). The MediDiet and standard interventions reduced constipation symptoms; however, the MediDiet provided additional benefit of increased dietary fiber intake and less intestinal inflammation.

Background: Point-of-care ultrasound (POCUS) has transformed inflammatory bowel disease (IBD) management, but the cost to purchase high-end equipment can be prohibitive., Aim: To assess prospectively the feasibility of POCUS using pre-existing mid-end ultrasound equipment without incurring additional cost., Methods: Consecutive IBD patients underwent POCUS with or without faecal calprotectin (FCP) using a mid-end ultrasound machine. If POCUS with or without FCP could not guide management, we performed additional ileocolonoscopy or cross-sectional imaging. We evaluated the impact of POCUS on IBD management and its correlation with ileocolonoscopy or cross-sectional imaging. We analysed pregnant, paediatric and post-operative patients separately., Results: Among 508 patients with IBD, we analysed 419 (60.4% Crohn's disease [CD]; 61.3% male, age [years]: 36 [18-78]) undergoing 556 POCUS sessions. POCUS with or without FCP independently influenced clinical management in 42.8% of patients with CD and 49.7% with ulcerative colitis (UC). POCUS helped avoid colonoscopy in 51.4% of patients with CD and 51.8% with UC, and cross-sectional imaging in 38.1% of suspected active small bowel CD. In patients with additional diagnostics, POCUS-based decisions remained unchanged in 81.2% with CD and 85% with UC. Sensitivity and specificity of POCUS compared to ileocolonoscopy were 80% and 94.4% for CD and 80.8% and 92.8% for UC, respectively. Sensitivity and specificity compared to cross-sectional imaging were 87.2% and 87.5%, respectively., Conclusion: POCUS using existing mid-end ultrasound equipment in low-resource settings influenced IBD clinical decision-making with excellent accuracy, often avoiding colonoscopy and cross-sectional imaging., (© 2024 John Wiley & Sons Ltd.)

Background: Following STRIDE-II recommendations, the discovery of novel noninvasive biomarkers, beyond the use of C-reactive protein (CRP) and fecal calprotectin, remains a medical need to further improve the monitoring of patients with inflammatory bowel disease (IBD). This study aims to evaluate the potential of serum lipopolysaccharide-binding protein (LBP) in monitoring IBD activity., Methods: This retrospective cross-sectional study included 69 IBD patients (43 Crohn's disease and 26 ulcerative colitis) and 82 controls. Serum LBP levels were measured by ELISA. Clinical, biological and endoscopic parameters were analyzed for IBD patients with no reports of missing data. Statistical tests, including nonparametric tests and receiver operating characteristic (ROC) curve analysis, were used to evaluate the diagnostic accuracy of LBP., Results: IBD patients displayed a significantly higher LBP median [29.6 μg/ml (19.8-38.8) in Crohn's disease and 22.8 (13.7-38.8) in ulcerative colitis] than controls [5.8 (4.7-7.3), P  < 0.001] with little overlapping distributions. In Crohn's disease patients, LBP levels gradually increased with endoscopic activity scores demonstrating a 1.7-fold rise in active patients compared to remitter patients ( P  = 0.02). LBP level exhibited a positive correlation with CRP ( ρ  = 0.75, P  < 0.001) as well as fecal calprotectin ( ρ  = 0.42, P  < 0.01), both of which further increased when excluding cases that did not match endoscopic activity., Conclusion: LBP might be a promising noninvasive biomarker for monitoring disease activity, especially in Crohn's disease patients. In clinical situations where current biomarkers lack sensitivity, LBP could be discriminative and help filling the gap for reliable therapeutic decisions., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Faecal biomarkers can be used to assess inflammatory bowel disease (IBD)., Aim: To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD., Methods: We included 65 patients with treatment-naïve, new-onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil-derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression., Results: All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79-0.89) and MPO (AUC 0.85, 95% CI: 0.80-0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006)., Conclusions: This study provides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Older subjects are at risk of elevated intestinal permeability (IP) which can lead to immune system activation and low-grade systemic inflammation. Dietary changes are a potential strategy to reduce IP. The MaPLE project evaluated the hypothesis that increasing (poly)phenol intake would beneficially impact on several important markers and pathways related to IP. The objective of the present study was to assess the effects of the MaPLE (poly)phenol-rich diet (PR-diet) on additional IP-related biomarkers and any relationships between biomarker responses., Methods: A randomised, controlled, crossover study was performed involving 51 participants (≥ 60 y) with increased IP, as determined by serum zonulin levels. Participants were randomly assigned to one of two intervention groups: a control diet (C-diet) or a PR-diet. Each intervention lasted 8 weeks and was separated by an 8-week washout period. For the present study, serum and faecal samples were used to measure zonula occludens-1 (ZO-1), occludin, adiponectin, calprotectin, faecal calprotectin, soluble cluster of differentiation 14 (sCD14), interleukin-6 receptor (IL-6R), and vascular endothelial-cadherin (VEC) levels using quantitative ELISA assays. Data were analysed using ANOVA, and Spearman and network correlation analysis were performed to identify the relationship among biomarkers at baseline., Results: Among the different markers analysed, a significant reduction was observed for faecal and serum calprotectin (p = 0.0378 and p = 0.0186, respectively) following the PR-diet, while a significant increase in ZO-1 was found (p = 0.001) after both the intervention periods (PR-diet and C-diet). In addition, a time effect was observed for VEC levels showing a reduction (p = 0.038) following the PR-diet. Based on network correlation analysis, two clusters of correlations were identified: one cluster with high levels of serum calprotectin, faecal calprotectin, sCD14, interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and bacterial DNAemia (16 S rRNA gene copies), with potential inflammatory-induced intestinal permeability. Differently, the other cluster had high levels of serum occludin, IL-6R, soluble intercellular adhesion molecule-1 (sICAM-1) and VEC, with potential inflammatory-induced endothelial dysfunction., Conclusions: Overall, this study provides further support to the hypothesis that a (poly)phenol-rich diet may help to ameliorate intestinal permeability-associated conditions. In this regard, calprotectin might represent a promising biomarker since it is a protein that typically increases with age and it is considered indicative of intestinal and systemic inflammation. Further research is needed to develop targeted (poly)phenol-rich diets against age-related gut dysfunction and inflammation., Trial Registration: 28/04/2017; ISRCTN10214981; https://doi.org/10.1186/ISRCTN10214981 ., (© 2024. The Author(s).)

Background: Azathioprine [AZA] effectively prevents postoperative endoscopic recurrence [ER] in Crohn's disease [CD]. However, the efficacy of AZA emerges after 3 months. Exclusive enteral nutrition [EEN] can maintain remission in CD. The present trial investigates whether AZA plus postoperative 3-month EEN is superior to AZA alone in preventing ER of CD., Methods: In total, 84 high-risk CD patients undergoing intestinal resection received AZA alone or AZA plus 3 months of EEN [AZA + EEN] postoperatively. The primary endpoint was the rate of ER at 12 months. Secondary endpoints included the rate of ER at 3 months, clinical recurrence [CR], CD activity index [CDAI] scores, faecal calprotectin [FC], and C-reactive protein [CRP]. Quality of life was assessed using Short Form-36 [SF-36] and the Inflammatory Bowel Disease Questionnaire [IBDQ]., Results: Patients in the AZA + EEN group exhibited significantly lower rates of ER compared to the AZA group at both 12 months (33.3% [13/39] vs 63.2% [24/38], P = 0.009) and 3 months (8.6% [3/35] vs 28.1% [9/32], P = 0.037) post-surgery. The rates of CR between the two groups at 3 and 12 months were similar. CDAI scores, FC, albumin level, and CRP were all comparable between the two groups. Quality of life was significantly higher in the AZA group than in the AZA + EEN group at 3 months but became comparable from 5 to 12 months postoperatively., Conclusion: In high-risk CD patients, combining AZA with postoperative 3-month EEN reduces 1-year ER but may temporarily impact quality of life. Further large-scale, long-term studies are warranted., Trial Number: NCT05214430., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Aims: Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study's primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment., Methods: The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model., Results: The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in the majority of its definitions, when adjusted for several confounding factors. Additionally, alongside FC, both IFX and CL demonstrated a significant impact on the temporal aspect of disease progression., Conclusion: In this 2-year real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that subclinical active inflammation, as mirrored by FC or CRP, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of disease progression. These findings underscore the need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The diagnosis of inflammatory bowel disease (IBD) in children and the need to distinguish between subtypes (Crohn's disease (CD) and ulcerative colitis (UC)) requires lengthy investigative and invasive procedures. Non-invasive, rapid, and cost-effective tests to support these diagnoses are needed. Faecal volatile organic compounds (VOCs) are distinctive in IBD. VOC profiles can be rapidly determined using a gas chromatography-sensor device (OdoReader©). In an inception-cohort of children presenting with suspected IBD, we directly compared the diagnostic fidelity of faecal calprotectin (FCP, a non-specific protein marker of intestinal inflammation) with OdoReader© VOC profiles of children subsequently diagnosed with IBD with matched controls diagnosed with other gastrointestinal conditions. The OdoReader© was 82% (95% confidence interval 75-89%) sensitive and 71% (61-80%) specific but did not outperform FCP (sensitivity 93% (77-99%) and specificity 86% (67-96%); 250 µg/g FCP cut off) in the diagnosis of IBD from other gastrointestinal conditions when validated in a separate sample from the same cohort. However, unlike FCP and better than other similar technologies, the OdoReader© could distinguish paediatric CD from UC (up to 88% (82-93%) sensitivity and 80% (71-89%) specificity in the validation set) and justifies further validation in larger studies. A non-invasive test based on VOCs could help streamline and limit invasive investigations in children.

Introduction: Although there are well-defined guidelines for the management of mild-to-moderate ulcerative colitis (UC), there are still unmet needs. For this reason, we conducted an international expert consensus to standardize the management of patients with mild-to-moderate UC and provide practical guidance to clinicians., Areas Covered: Based on Delphi methodology, 15 statements were approved after two rounds of voting, addressing several aspects of disease management from sequencing to treatment duration, from monitoring to optimization techniques and safety profile., Expert Opinion: Growing knowledge of mild-to-moderate UC has led to the development of new ambitious outcomes such as histological remission and disease clearance. Furthermore, noninvasive tools for patient monitoring such as fecal calprotectin and intestinal ultrasound are now available. Their implementation in clinical practice will allow clinicians to tightly monitor disease activity and promptly adapt treatment, avoiding complications and disease progression and targeting better disease control.

Background and Study Aims: Close monitoring of disease activity in IBD patients is essential to avoid long term complications. Although endoscopic assessment is the ideal monitoring tool, the usage of noninvasive biomarkers is more practical and patient friendly. We aimed to study the performance of Interleukin-6(IL-6) and Serum Amyloid A(SAA) as serum biomarkers in assessment of the disease activity of IBD patients in correlation to C-reactive protein (CRP), Fecal Calprotectin (FC) and endoscopic indices., Methods: 83 IBD (26 CD and 57 UC) patients on stable treatment regimen were recruited. Serum markers included CRP, CBC, IL-6, SAA were analyzed, together with FC. These markers were compared with the endoscopic and clinical disease parameters. Harvey-Bradshaw Index (HBI) and the Simple Clinical Colitis Activity Index (SCCAI) were used to assess clinical activity in CD and UC patients, respectively. Endoscopic activity was recorded using the Simple Endoscopic Score (SES) for Crohn's disease or the Mayo Endoscopic Score (MES) for ulcerative colitis., Results: In prediction of disease activity, IL-6, SAA and CRP demonstrated good area under receiver operating characteristics (AUC) (>0.7), with FC being the best (0.94) for endoscopically active disease (P < 0.01). Combining FC and IL-6 or SAA improved its discriminative accuracy with an AUC (∼0.96)., Conclusions: FC most accurately predicts endoscopic disease activity in IBD patients, in comparison to other studied serological biomarkers. The serum IL-6 and SAA are potential predictors of endoscopic disease activity, and they might be valuable for assessment of disease activity. Finally, a composite score of FC and SAA or IL-6 can increased its diagnostic accuracy., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Some data suggest the existence of intestinal inflammation in patients with non-celiac wheat sensitivity (NCWS). We aimed to verify whether fecal calprotectin (FCP), a marker of intestinal inflammation, could be used to confirm this inflammatory status and to test its diagnostic performance in differentiating NCWS from irritable bowel syndrome/functional dyspepsia (IBS/FD). We conducted a multicenter study, comparing NCWS patients, diagnosed by a double-blind placebo-controlled wheat challenge, with IBS/FD subjects. In the retrospective phase, FCP values were analyzed to define the prevalence of its positivity and its role as a NCWS diagnostic biomarker. In the prospective phase we tested the effects of a strict 6-month wheat-free diet (WFD) on FCP values. 31.3% (n = 63/201) of NCWS patients had above normal FCP values (NCWS FCP +), whereas all IBS/FD patients proved negative (P = 0.0001). FCP using a cut-off value > 41 µg/g showed a 58.6% sensitivity and a 98.0% specificity (AUC 0.755, 95% C.I. 0.702-0.837) in distinguishing NCWS from IBS/FD patients. Of the 63 NCWS FCP+, 65.1% had negative FCP values after ≥ 6 months of WFD, with a significant reduction in FCP values (P < 0.0001). All NCWS FCP- subjects still preserved negative FCP values after ≥ 6 months of WFD. Our study showed that FCP can be a useful but supplementary diagnostic marker for differentiating between NCWS and IBS/FD. Strict WFD adherence reduced FCP values, normalizing them in 65.1% of NCWS FCP + subjects. These data suggest the existence of two NCWS subgroups: NCWS FCP + characterized by a probable predominantly inflammatory/immunologic pattern and NCWS FCP- featuring non-immuno-mediated etiopathogenetic mechanisms. (Registration number NCT01762579)., (© 2024. The Author(s).)

Background: Acute severe ulcerative colitis (ASUC) is a medical emergency for which colectomy is required in patients who do not respond to rescue therapy. While previous studies have predominantly focused on predicting outcome to first-line corticosteroid therapy, there is a need to understand the factors associated with response to rescue therapies in order to improve clinical outcomes. We reviewed the evidence regarding factors associated with response to rescue therapy in adults with ASUC and identified future directions for research., Methods: A systematic search of the literature was conducted, and 2 reviewers independently assessed studies for inclusion., Results: Of 3509 records screened, 101 completed studies were eligible for inclusion. We identified 42 clinical, hematological, biochemical, endoscopic, or pharmacological factors associated with response to rescue therapy. Older age (≥50 years), thiopurine experience, and cytomegalovirus or Clostridioides difficile infection were associated with a higher risk of nonresponse to rescue therapy. Biochemical factors associated with poorer response included an elevated C-reactive protein (CRP) ≥30mg/L on admission, hypoalbuminemia and an elevated ratio of CRP to albumin. Severe endoscopic findings, including a Mayo endoscopic score of 3 or Ulcerative Colitis Endoscopic Index of Severity ≥5, portended poorer outcomes. The role of fecal calprotectin and therapeutic value of measuring infliximab drug levels in ASUC remain to be defined., Conclusions: Response to rescue therapy can be predicted by several specific factors, which would aid clinical decision-making. Existing and emerging factors should be integrated within predictive and prognostic models to help improve clinical outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Although increasing studies have reported that dose escalation can improve treatment response to ustekinumab in patients with Crohn's disease (CD), their strategies mainly focus on maintenance regimen. Evidence of ustekinumab dose escalation in induction regimen, particularly in severe CD, remains limited. This study evaluated the efficacy and safety of intravenous ustekinumab with 2 initial doses in patients with severely active CD., Methods: A retrospective observational study of 99 adult patients with severe CD treated with ustekinumab from 3 IBD centers included 48 patients with standard and 51 with optimized induction treatment. Clinical outcomes, inflammatory biomarkers including fecal calprotectin (FC) normalization, and endoscopic outcomes were evaluated at weeks 16 and 48. Adverse events and treatment decisions after initial induction were also collected., Results: Compared with the standard group, 2 initial intravenous injections of ustekinumab achieved higher clinical response (92.2%, 47 of 51, P = .656), clinical remission (88.2%, 45 of 51, P = .221), endoscopic response (75.8%, 25 of 33, P = .125), and FC normalization (70.6%, 36 of 51, P = .138) at week 16. The mucosal healing rate at week 16 (63.6%, P = .022) was statistically higher in the optimization group. At week 48, patients with optimized treatment achieved higher clinical response (80.4%, 41 of 51, P = .003), clinical remission (70.6%, 36 of 51, P = .007), FC normalization (66.7%, 34 of 51, P = .031), endoscopic response (72.7%, 24 of 33, P = .006), and mucosal healing (57.6%, 19 of 33, P = .004). At the last follow-up, 82.4% of optimally treated patients adhered to continued treatment with ustekinumab (P < .001)., Conclusions: Optimization of ustekinumab by 2 initial intravenous inductions is more effective than standard therapy for adult patients with severe CD., (Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation 2023.)

Aims: This study investigated how post-operative ustekinumab levels relate to surgery type, endoscopic, biochemical, and clinical outcomes in patients with Crohn's Disease., Methods: A retrospective study of patients with Crohn's Disease with a disease-related operation between 2016 and 2022 assessed outcomes based on ustekinumab levels. Patients were included if they had an ustekinumab trough level within two years post-operatively. Patients were separated into groups based on whether their ustekinumab trough levels were adequate, defined as ≥ 4 μg/mL, or suboptimal < 4 μg/mL. A subset of patients with ustekinumab levels taken within two years both before and after surgery was compared to non-surgical treatment-escalated controls outside the initial patient set. Harvey-Bradshaw index was used to evaluate clinical disease activity. Rutgeert's and Simple Endoscopic Score for Crohn's Disease was used to evaluate endoscopic disease activity. C-reactive protein and fecal calprotectin values were collected to evaluate the molecular inflammatory disease state. CBC data were used to evaluate anemia., Results: Forty-four patients were identified, which had ustekinumab levels after Crohn's Disease-related surgery. Twelve of these patients had pre-operative levels and were compared to 26 non-surgical treatment-escalated controls. No relationship between ustekinumab levels and endoscopic or clinical disease activity post-operatively was found. This also held true when looking at different surgery types. Adequate levels of ustekinumab post-operatively yielded lower risk of anemia. Surgery itself did not have an impact on ustekinumab levels., Conclusions: This study provided new insights into how post-operative ustekinumab levels impact several factors in patients having undergone Crohn's disease-related surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Synovial calprotectin is a promising biomarker for diagnosing chronic periprosthetic joint infections (PJIs), but its diagnostic value has not been directly compared to synovial leukocyte count and polymorphonuclear neutrophils. This study aimed to: (1) evaluate and compare the diagnostic accuracy between these markers in patients undergoing revision arthroplasty for chronic PJI or aseptic reasons; and (2) determine the best rule-out and rule-in test for PJI., Methods: Synovial fluid samples from patients undergoing revision arthroplasty in hip and knee joints were collected and analyzed. Patients diagnosed with an acute PJI, patients treated with antibiotics 2 weeks prior to revision surgery, and/or patients who had active inflammatory joint disease were excluded. Periprosthetic joint infections were diagnosed based on the presence of a sinus tract and/or positive intraoperative cultures according to the European Bone and Joint Infection Society microbiological criteria., Results: A total of 137 patients were included, of whom 19 (14%) were diagnosed with a PJI. Overall, synovial calprotectin had the highest diagnostic accuracy of all studied markers (area under the curve 96%). Synovial calprotectin, with a cutoff of 50 mg/L, had the highest negative predictive value of 100%. However, PMNs (> 80%) combined with a leukocyte count (> 3,000 cells/μL) showed the highest positive likelihood ratio of an infection (PLR 17)., Conclusions: Synovial calprotectin is the most accurate biomarker for ruling out a chronic PJI, while the combination of synovial leukocyte count and PMN is most reliable for ruling in a chronic PJI., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Inflammatory bowel diseases are chronic pathologies characterized by a complex interplay of genetic and environmental factors, as well as aberrant immune responses. This study aimed to investigate inflammation markers' seasonality and association with disease exacerbation episodes in patients with Crohn's disease and ulcerative colitis., Methods: 284 patients were classified based on clinical, endoscopic, and histopathological criteria. Systemic inflammation was evaluated using C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and chitotriosidase, while fecal calprotectin was measured to assess intestinal inflammation. Serum vitamin D levels and the seasonality of an activity score that combines several clinical and biological parameters were also evaluated., Results: The peak number of patients reporting endoscopic activity occurred in autumn for Crohn's disease (82%) and spring for ulcerative colitis (95%). Regarding histological activity, spring saw the highest number of patients for both diseases (72% for Crohn's disease; 87% for ulcerative colitis). Most of the inflammatory markers exhibited lower values during winter. Systemic inflammatory markers follow a slightly different trend than fecal calprotectin and differ in the two pathologies. The maximum values of intestinal inflammation were observed in autumn for Crohn's disease (784 µg/g) and in spring for ulcerative colitis (1269 µg/g). Serum vitamin D concentrations were consistently low throughout the year. Statistical analysis revealed differences between the seasons for CRP and ESR (P < 0.05)., Conclusion: The evolution of flares and inflammatory markers in Crohn's disease and ulcerative colitis displayed distinct seasonal patterns. Systemic inflammation did not consistently parallel intestinal inflammation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Endoscopy is still the gold, standard for assessing disease activity in Crohn's disease (CD). Its invasiveness, poor acceptability, and cost limit its use in the era of tight control and treat-to-target management. Fecal calprotectin (FC) and intestinal ultrasound (IUS) are non-invasive alternatives to colonoscopy to assess disease activity. We aimed to evaluate the performance of IUS and FC to assess mucosal healing in CD., Methods: All consecutive CD patients who underwent colonoscopy for mucosal healing assessment and IUS and/or FC within four weeks between September 2019 and April 2022 were included in a prospective cohort. The bowel-wall thickness (BWT) and color Doppler signal (CDS) were assessed for each segment. Endoscopic remission was defined by a CDEIS score < 3., Results: In total, 153 patients were included, of whom 122 showed endoscopic mucosal healing. Eighty-two (53.6 %) were female, the median was age 36 years (IQR, 28-46), and the median disease duration was 10 years (IQR, 4-19). The sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of a BWT < 3 mm to predict endoscopic mucosal healing were 56 %, 88 %, 95 %, and 36 %, respectively (patients misclassified as mucosal healing, 2.5 %). The best FC threshold (< 92.9 µg/g) provided similar results: 77 %, 89 %, 96 %, and 67 %, respectively (patients misclassified, 2.2 %). The association of an FC < 250 µg/g with a BWT < 3 mm and the absence of CDS increased the Sp and PPV: Se 58 %, Sp 95 %, PPV 97 %, VPN 43 %; patients misclassified, 1.3 %., Conclusion: Noninvasive evaluation of mucosal healing by IUS or calprotectin efficiently identifies patients with CD who have achieved endoscopic mucosal healing., Competing Interests: Declaration of competing interest CY: consultant and lecture fees from Abbvie, Takeda, Janssen, Amgen, and Galapagos MF: consultant and lecture fees from Abbvie, Takeda, Janssen, Amgen, Galapagos, Gilead, Biogen, Fresenius, Pfizer, Lilly, Celltrion, Ferring, Tillots, and Nordic Pharma VH: AAA, Merck KGaA, Amgen, Servier, Deciphera, Ipsen, and Pierre Fabre The other authors have nothing to declare., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background and Study Aims: Isolated small bowel Crohn's disease (SBCD) is reported to have a worse prognosis compared to other CD phenotypes. The aim of this study was to understand the correlation between Isolated SBCD and ileocolonic disease with blood and faecal biomarkers and also to identify differences in outcome and management between the two phenotypes., Patients and Methods: Patients with ileocolonic or isolated small bowel Crohn's Disease (SBCD) were identified from an existing capsule endoscopy (CE) database. Harvey Bradshaw Index (HBI), biomarkers: c-reactive protein (CRP) and faecal calprotectin (FC), Lewis score and findings on CE and subsequent follow up data were collected. SPSS was used to analyse the data., Results: In total 248 patients were included in the study. Patients were split into two groups- Isolated SBCD with 178 patient (median age 44 years (IQR 31-56); 41.5 % male) and Ileocolonic Crohn's with 70 patients (median age 31 years (IQR 22.7-49); 31.5 % male). A new diagnosis of SBCD was made in 38.7 % (n = 96), whilst 60.0 % (n = 144) had established CD. Patients with ileocolonic disease had a higher HBI in comparison to isolated SBCD [HBI = 7 (IQR 5-10) vs HBI = 6(IQR 4-9); P = 0.04 ]. There was no significant difference in the FC levels between isolated SBCD and ileocolonic disease [136ug/g (IQR 53.8-363.3) vs 171ug/g (IQR 68.5-485.5); p = 0.98]. In isolated SBCD group, 30.3 % (n = 54) CE showed proximal disease, 96 % (n = 171) showed distal disease and 26.4 % (n = 47) showed extensive disease. SBCE was superior to MRI at diagnosing proximal SBCD (P < 0.01). On multivariate logistic regression, we did not identify any predictors of disease severity defined as Lewis score > 790. Following SBCE, 68.5 % (n = 170) of the total patients had a management change. This included commencement or dose escalation of corticosteroids in 123 (49.5 %) patients, azathioprine in 80 (33.3 %) patients, methotrexate in 22 (9.1 %) patients and biological therapy in 110 (44.3 %) patients. HBI predicted a change in management (p < 0.01)., Conclusion: CE is an important modality for the diagnosis of active SBCD. It also helps guide treatment in patients identified with active disease., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Accurate early detection of ileocolonic lesions in patients with chronic lower gastrointestinal symptoms (LGISs) is often difficult due to the rarity of early-stage alarm signs. This study assesses the effectiveness of noninvasive blood and stool biomarkers in diagnosing ileocolonic lesions in patients with chronic LGISs undergoing colonoscopy., Methods: We conducted a prospective study between April 2020 and July 2022 involving patients with LGISs lasting a month or more. Before colonoscopy, we gathered clinical data, blood samples for C-reactive protein (CRP) and stool samples for fecal immunochemical test (FIT) and fecal calprotectin (FC) analysis., Results: Of 922 participants analyzed (average age 62 years, 37% male), 130 (14.1%) had significant colonoscopy findings, including cancer, advanced adenoma, and inflammatory conditions. Test effectiveness showed an area under the curve of 0.630 for alarm features, 0.643 for CRP, 0.781 for FIT, and 0.667 for FC. Combining stool tests with alarm features improved diagnostic precision. Those without alarm features had a high negative predictive value of 0.97 with low threshold FIT and FC, missing minimal significant lesions, and no cancer. For patients with alarm features, dual high-cutoff test positivity showed a positive predictive value of 0.67. Adding CRP to fecal tests did not enhance accuracy., Discussion: FIT and FC are valuable in evaluating LGISs. Negative results at low cutoffs can delay colonoscopy in limited resource settings while positive results at dual high cutoffs substantiate the need for the procedure., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Especially for pediatric patients, proxies of mucosal inflammation are needed. The Pediatric Ulcerative Colitis Activity Index (PUCAI) has been established to predict clinical and endoscopic disease activity. However, histologic inflammation might persist. We applied a special variable selection technique to predict histologic healing in pediatric ulcerative colitis (UC) as parsimoniously (but still as precisely) as possible. The retrospective analysis included data from two study cohorts, comprising 91 visits from 59 pediatric patients with UC. A Bayesian ordinal regression model was used in combination with a projection-predictive feature selection (PPFS) to identify a minimal subset of clinical and laboratory parameters sufficient for the prediction of histologic disease activity. Following the PPFS, CEDATA-GPGE patient registry data were analyzed to investigate the relevance of the selected predictors in relation to PUCAI and Physician Global Assessment (PGA) in up to 6697 patient visits. Fecal calprotectin (FC) and platelet count were identified as the minimal subset of predictors sufficient for prediction of histologic disease activity in pediatric UC. FC and platelet count also appeared to be associated with increasing disease activity as measured by PUCAI and PGA in the CEDATA-GPGE registry. Based on the selected model, predictions can be performed with a Shiny web app.  Conclusion: Our statistical approach constitutes a reproducible and objective tool to select a minimal subset of the most informative parameters to predict histologic inflammation in pediatric UC. A Shiny app shows how physicians may predict the histologic activity in a user-friendly way using FC and platelet count. To generalize the findings, further prospective studies will be needed. What is Known: • Histologic healing is a major endpoint in the therapy of ulcerative colitis (UC). • The PUCAI score has been established to predict disease activity in pediatric UC but is not suitable for the prediction of histologic healing. What is New: • Our Bayesian ordinal regression model in combination with a projection-predictive feature selection is a reproducible and objective tool to select the minimal subset of clinical and laboratory parameters to predict histologic inflammation in pediatric UC. • Histologic inflammation in pediatric UC can be non-invasively predicted based on the combination of fecal calprotectin levels and platelet count., (© 2024. The Author(s).)

Cerebral palsy (CP) results in non-progressive damage to the central nervous system, leading to functional disorders of the gastrointestinal tract and requiring enteral nutrition via gastrostomy in some patients. The aim of the study was to assess the impact of enteral nutrition on intestinal inflammation expressed by stool calprotectin and intestinal permeability determined by fecal zonulin and IFABP, and to determine whether CP affects these parameters. The study group consisted of 30 children with CP, fed enterally (Cerebral Palsy Enteral Nutrition-CPEN), and two reference groups: 24 children with CP, fed orally with a standard diet (CPC-Cerebral Palsy Controls) and 24 healthy children (HC-healthy controls). The differences between these groups and between the combined CP groups (CPG and CPEN + CPC) and HC were analyzed. Fecal zonulin, calprotectin, and intestinal fatty acid-binding protein 2 (IFABP2) levels were determined by ELISA. The concentrations of fecal calprotectin and zonulin were significantly higher in the CPEN group than in the CPC group ( p = 0.012, p = 0.025). When comparing the CPG ( n = 53) with the HC group ( n = 24), statistically significant differences were observed for calprotectin ( p = 0.000018, higher in the CPG) and IFABP ( p = 0.021, higher in HC). Enteral nutrition was associated in our cohort with increased fecal calprotectin and zonulin. Children with cerebral palsy presented with increased fecal calprotectin but not increased intestinal permeability expressed by stool zonulin.

Investigating the gut microbiome and metabolome frequently requires faecal samples, which can be difficult to obtain. Previous studies have shown that rectal swabs are comparable to faecal samples for analysing gut microbiota composition and key metabolites. In this study, 3D printed rectal swabs were compared with conventional flocked swabs and faecal samples, due to the potential advantages 3D printing as a technique offers for swab production and development. 16S rRNA gene sequencing, qPCR and metabolite profiling (using 1 H-NMR spectroscopy) were performed on swab and faecal samples from healthy participants. Faecal calprotectin and total protein analysis were performed on samples from inflammatory bowel disease (IBD) patients. There were no significant differences between both swab types and faecal samples when assessing key measures of alpha and beta diversity, and differences in the abundance of major phyla. There was a strong correlation between both swab types and faecal samples for all combined metabolites detected by NMR. In IBD patients, there was no significant difference in faecal calprotectin and total protein levels between both swab types and faecal samples. These data lead us to conclude that 3D printed swabs are equivalent to flocked swabs for the analysis of the gut microbiome, metabolome and inflammation., (© 2024. The Author(s).)

Purpose: Ulcerative colitis (UC) is an inflammatory bowel disease with an unclear etiology that can lead to irreversible changes in distal colonic function in chronic patients. This study investigated anorectal function in recurrent UC patients and identified influencing factors., Methods: This prospective study enrolled 33 recurrent UC patients and 40 newly diagnosed patients from January 2019 to December 2022. Data collection included clinical records, scores, and anorectal function assessments. Regression analyses were used to identify factors impacting anorectal function., Results: Recurrent UC patients had higher baseline CRP and fecal calprotectin levels, increased anxiety and depression, and more severe fecal incontinence. They also had lower BMIs, serum Hb and albumin (ALB) levels, and Inflammatory Bowel Disease Questionnaire scores than did initial-onset UC patients. Multivariate linear regression analysis revealed that long disease duration (coef. - 0.376, P < 0.001) and high fecal calprotectin level (coef. - 0.656, P < 0.001) independently influenced the initial sensation threshold in recurrent UC patients. Additionally, high fecal calprotectin (coef. - 0.073, P = 0.013) and high Zung Self-Rating Anxiety Scale score (coef. - 0.489, P = 0.001) were identified as two independent determinants of the defecation volume threshold. For the defecation urgency threshold, the independent factors included high disease duration (coef. - 0.358, P = 0.017) and high fecal calprotectin level (coef. - 0.499, P = 0.001). Similarly, the sole independent factor identified for the maximum capacity threshold was high fecal calprotectin (coef. - 0.691, P = 0.001)., Conclusion: Recurrent UC patients had increased rectal sensitivity and compromised anorectal function, which significantly impacted quality of life. Proactively managing the disease, reducing UC relapses, and addressing anxiety are effective measures for improving anorectal function in these patients., (© 2024. The Author(s).)

Background/aims: Studies on elective switching to the subcutaneous (SC) formulation of infliximab revealed comparable efficacy and safety and higher infliximab level than those exhibited by intravenous (IV) infliximab. However, no studies have reported on the effectiveness of SC switching in ulcerative colitis (UC) patients who experienced IV infliximab failure during maintenance treatment., Methods: This retrospective study included UC patients who had been switched to SC infliximab because of IV infliximab failure, between January 2021 and January 2023. Group A was defined as having clinically and biochemically active UC (secondary loss of response), and group B consisted of patients with stable symptoms but biochemically active UC., Results: Twenty-three patients met the inclusion criteria: 15 in group A and eight in group B. The serum infliximab levels significantly increased after SC switching in both groups. The electively switched group also exhibited increased infliximab levels after SC switching. Patients in group A showed improved partial Mayo score with a significant decrease in fecal calprotectin and C-reactive protein after switching. In group B, the fecal calprotectin level significantly decreased without clinical relapse after switching. A high proportion of patients (≥80%) in both groups achieved clinical and/or biochemical responses at the last follow-up. During the follow-up period, only two patients in group A discontinued SC infliximab, and only one complained of severe injection site reaction., Conclusions: In UC patients who experience IV infliximab failure during maintenance treatment, switching to SC infliximab may be a promising option because of better efficacy and safety.

Objectives: To investigate the role of calprotectin S100 A8/A9 complex in evaluating the condition of children with severe Mycoplasma pneumoniae pneumonia (SMPP)., Methods: A prospective study was conducted among 136 children with Mycoplasma pneumoniae pneumonia (MPP) and 30 healthy controls. According to the severity of the condition, the children with MPP were divided into mild subgroup (40 children) and SMPP subgroup (96 children). The levels of S100 A8/A9 complex and related inflammatory factors were compared between the MPP group and the healthy control group, as well as between the two subgroups of MPP. The role of S100 A8/A9 in assessing the severity of MPP was explored., Results: The MPP group had a significantly higher level of S100 A8/A9 than the healthy control group, with a significantly greater increase in the SMPP subgroup ( P <0.05). The multivariate logistic regression analysis showed that the increases in serum C reactive protein (CRP) and S100A8/A9 were closely associated with SMPP ( P <0.05). The receiver operating characteristic (ROC) curve analysis showed that the combined measurement of serum S100 A8/A9 and CRP had an area under the ROC curve of 0.904 in predicting SMPP, which was significantly higher than the AUC of S100 A8/A9 or CRP alone ( P <0.05), with a specificity of 0.718 and a sensitivity of 0.952., Conclusions: S100 A8/A9 is closely associated with the severity of MPP, and the combination of S100 A8/A9 with CRP is more advantageous for assessing the severity of MPP in children.

Objective: To optimize and evaluate methods for the detection of the inflammatory biomarkers myeloperoxidase (MPO) and calprotectin (CP) in equine feces by ELISA., Animals: Healthy horses (n = 28) and horses with intestinal inflammation (n = 10)., Methods: Feces were suspended in buffer to create fecal supernatant. Serum and fecal supernatant were analyzed using ELISA kits validated for the detection of MPO and CP in equine serum. Assay validation steps included intra- and interassay variability (coefficient of variation [CV]), dilution linearity, spike recovery, and sample type correlation. Variations in sample handling protocols (centrifugation speed, extraction buffer, and filtration) were evaluated., Results: 17 paired fecal and serum samples were used for initial analysis (10 healthy horses, 7 colitis). Previously reported sample handling protocols resulted in detectable MPO and CP but poor CV, linearity, and spike recovery. There was a linear correlation between serum and fecal samples for CP but not MPO. There was a significant difference between the concentration and CV of alternative sample handling protocols for CP and MPO, with improved CV for CP (2.1% to 18.6%) but not MPO (14.4% to 53.4%). Processing fresh feces with a fecal extraction buffer and filtration of supernatant resulted in the best CV (0.5% to 3.8%) and recovery (45% to 64%) for CP. Detection of MPO was inconsistent regardless of method., Clinical Relevance: There are few reliable diagnostic modalities for inflammation of the equine large colon. Findings support quantification of CP in equine feces using the described ELISA kit and protocol. With additional study to establish reference interval and clinical utility, the fecal inflammatory biomarker CP may allow for noninvasive quantification of intestinal inflammation in horses.

Background: Oral health problems have increased among older adults. Oral hypofunction is characterized by seven signs and symptoms: oral uncleanness, oral dryness, decline in occlusal force, decline in the movement function of the tongue and lips, decline in tongue pressure, decline in masticatory function, and decline in swallowing function, the latter being a significant risk factors for oral frailty. Recent research has suggested that salivary biomarkers can be used to assess not only oral diseases, including dental caries and periodontitis, but also systemic diseases, such as cancer and diabetes mellitus. This cross-sectional study investigated the relationship between oral hypofunction and the levels of salivary biomarkers., Methods: In total, 116 patients, aged 65 years or older, were included in this cross-sectional study. If three or more signs or symptoms in seven kinds of tests met the criteria of each test, oral hypofunction was diagnosed. The levels of biomarkers in the saliva collected from the patients were analyzed using an enzyme-linked immunosorbent assay., Results: In total, 63.8% of patients were diagnosed with oral hypofunction. Multivariable linear regression analysis showed that calprotectin levels in the saliva were significantly related to oral moisture and masticatory function. Furthermore, 8-OHdG levels in saliva were associated with the movement function of the tongue and lips and oral hygiene level, and salivary AGE correlated only with the movement function of the tongue and lips. Multiple logistic regression analysis revealed that calprotectin levels in the saliva were significantly correlated with the prevalence of oral hypofunction, even after adjusting for age, sex, and periodontal status. However, none of the biomarker levels in the saliva had a significant relationship with the number of examinations outside the reference range., Conclusions: Calprotectin, 8-OHdG, and AGE levels are associated with oral hypofunction in older adults., (© 2024. The Author(s).)

Background and Objectives : Irritable bowel syndrome (IBS) is an invasive and potentially disabling syndrome characterized by a multitude of symptoms capable of reducing the quality of life of patients. Among the most disabling symptoms of IBS is certainly physical pain, which manifests itself mainly at the abdominal level but can also appear in other areas of the body, particularly in the form of chronic low-back pain (CLBP). Among the non-invasive methods of treating organ-specific pathologies and organ-related musculoskeletal problems, the use of Bioresonance Therapy (BT)-based on the administration of self-modulating Extremely Low-Frequency Electromagnetic Fields, capable of determining a rebalance of bio-electrical and metabolic activity in the presence of various functional alterations-is currently gaining acceptance. Therefore, we decided to monitor results obtained from patients suffering from IBS and CLBP subjected to a cycle of treatments with BT. Materials and Methods : We monitored 20 patients (12 women and 8 men, average age of 51 years) suffering from CLBP and other visceral symptoms related to IBS. Patients were monitored through the use of the Bristol Stool Form Scale (BSFS), the Fecal Calprotectin test and the Short-Form Health Survey 36 (SF-36), collected before (T0) and after (T1) the execution of the cycle of treatments. They undertook a treatment protocol consisting of eight sessions of BT carried out over about a month. Results : At the end of the treatments with BT, it was possible to observe a general and significant improvement in all the parameters observed, as well as a close inversely proportional correlation between the Calprotectin values detected and the quality of life experienced by the patients in relation to their perceived IBS symptoms. Conclusions : Overall, our pilot study would seem to suggest a potential beneficial effect of BT in modulating organic and musculoskeletal symptoms derived from IBS.

Background: There is growing evidence of the role of the mycobiome in inflammatory bowel disease (IBD). Variations within phenotypes and activity and with prognosis have been poorly studied., Methods: A total of 111 individuals were prospectively enrolled: 89 IBD patients (52 ulcerative colitis and 37 Crohn's disease [CD]) and 22 healthy individuals. Disease characteristics were collected and a fecal calprotectin >100 μg/mg was considered indicative of activity. A subset of patients was followed for 6 ± 2 years. Disease course was designated as either complicated or uncomplicated based on the need of intensified medication and/or surgery. ITS sequencing was performed targeting the ITS1 region., Results: We found lower Ascomycota/Basidiomycota ratio in IBD. Patients showed a marked increase in Candida dublinensis and Ca albicans and were depleted of Aspergillus rubrobrunneus and Penicillium brevicompactum (P ≤ .001) Saccharomyces was predominant in total colitis and Penicillium in proctitis. Several Penicillium species were depleted in total colitis vs proctitis. Ileal CD patients were enriched in Debaromyces hansenii and depleted of Ca tropicalis (P ≤ .001). Ca albicans was overrepresented in inflammatory (B1) vs fibrostenosing (B2) CD. Ca dublinensis was more abundant in active patients and correlated positively with fecal calprotectin and neutrophil gelatinase-associated lipocalin, while S pastorianus correlated inversely with activity. Ca sake was associated with complicated disease and increased abundance of Cryptococcus carnescens with the need for surgery in CD., Conclusions: This study shows important differences in the mycobiome in IBD and within phenotypes. Selected fungal species were associated with complicated disease and the need of surgery in CD. This work adds to our understanding of the role of fungi in IBD, with potential clinical implications., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Transabdominal ultrasonography and transperineal ultrasonography (TPUS) appear correspond to colonoscopy (CS) for evaluating ulcerative colitis (UC) activity, but their utility in UC diagnosis remains unclear. This research compared the accuracy of TPUS and CS for assessing rectal activity and differentiating noninflammatory bowel disease proctitis from UC in pediatric cases., Methods: The study is a blinded, prospective, and controlled trial. Prospectively, values of fecal calprotectin (FCP) and findings of the TPUS and CS were compared between child cases of UC and non-IBD proctitis. Findings of rectal wall thickening (RWT), rectal wall flow (RWF) on power Doppler, and microvascular signal at wall circumference (MSWC) on monochrome superb microvascular imaging assessed using TPUS were compared with the CS., Results: Thirty patients with Mayo endoscopic subscore (MES) 0 to 1 UC, 57 with MES 2 to 3 UC, and 44 with proctitis were registered. Fecal calprotectin, RWF, and MSWC indicated significant differences among the groups (P < .05). Rectal wall thickening showed no significant difference between MES 0-1 and proctitis (P = .76). Rectal wall thickening and MSWC were independent predictors of endoscopic activity of UC, resulting in a sensitivity and specificity of 100% for RWT ≥4.5 mm and positive MSWC. Fecal calprotectin and RWF were independent predictors for differentiating MES 0 to 1 and proctitis, and FCP and RWT were independent predictors for differentiating MES 2 to 3 and proctitis. Sensitivity and specificity were 77.2% and 80.9%, respectively, for FCP >242.5 μg/g and RWF negative; and they were both 100% for RWT >4.1 mm and MSWC positive., Conclusions: Transperineal ultrasonography with mSMI may enable the evaluation of rectal activity and differentiation of UC from non-IBD proctitis with accuracy comparable to endoscopy., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve nutritional status and are of importance in achieving normal growth among younger children with CF. The study was designed to examine CFTR modulator-associated changes in nutrition status, including bile acids and fatty acids after lumacaftor/ivacaftor therapy for 24 weeks., Methods: Children 2 to 5.9 years were recruited from US and Canadian CF Centers. Eligible children were lumacaftor/ivacaftor naïve and approved to initiate therapy. Anthropometrics, diet, energy expenditure, nutrition biomarkers, pancreatic status, serum and fecal calprotectin, serum bile acids and plasma fatty acids were measured. Changes from baseline at 12 and 24 weeks were examined using mixed effects linear regression modeling., Results: Weight-for-age z-score (WAZ) increased at 12 (0.15 ± 0.1, p = 0.01) and 24 weeks (0.23 ± 0.1, p = 0.001) from baseline following modulator therapy. Head circumference-for-age (HCZ) increased at 12 weeks compared to baseline (0.22 ± 0.1, p = 0.03) and subscapular Z score increased from baseline at 24 weeks following therapy (0.33 ± 0.1, p = 0.02). There were no changes in energy expenditure. Serum total bile acids (6.7 ± 2.0, p = 0.001), chenodeoxycholic acid (CDCA) (2.4 ± 1.1, p = 0.001), and cholic acid (CA) (3.5 ± 0.8, p < 0.0001) increased at 24 weeks compared to baseline. Fecal calprotectin decreased at 12 and 24 weeks compared to baseline (-463 ± 310, p = 0.03 and 566 ± 347, p = 0.047). A number of plasma fatty acids changed over the course of 24 weeks of therapy. Noteably, alpha-linolenic acid (ALA) decreased at 12 and 24 weeks (-24 ± 10,p = 0.03 and -18 ± 10, p = 0.02, respectively)., Conclusions: Overall, young children experienced favorable changes in nutritional and growth, with the exception of plasma ALA status in the first 24 weeks of lumacaftor/ivacaftor therapy., Competing Interests: Declaration of competing interest All authors disclose they have no conflicts of interest related to this project and manuscript. The funding sources had no role in study design, analysis or drafting of the manuscript., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To identify possible tests along with their accuracies that may be used to diagnose irritable bowel syndrome., Methods: The systematic review comprised literature search on Cochrane Library, PubMed, Science Direct and Elsevier databases for randomised controlled trials and cohort studies conducted from January 1, 2015, to December 31, 2022, using appropriate key words and Boolean operators. Focus was kept on studies that reported irritable bowel syndrome diagnosis as the primary outcome. The risk of bias was assessed using quality assessment, data abstraction, and synthesis version 2., Results: Of the 2,798 studies initially identified, 10(0.35%) were analysed in detail. Of them, 4(40%) used enzyme-linked immunosorbent assay kits to test for anti-cytolethal distending toxin B and anti-vinculin levels, 2(20%) used the kits for serum cytokine profiling and serum calprotectin levels, and 4(40%) used either magnetic resonance imaging scans, faecal metabolic profiling, intestinal biopsy analysis with immunostaining or polymerase chain reaction for differential transferribonucleic acid-derived small ribonucleic acid. Out of the 4(40%) studies on anti-cytolethal distending toxin B and anti-vinculin levels, optical densities >1.56 and >1.60 recorded 100% specificity for irritable bowel syndrome with diarrhoea, but sensitivity was 22%. In contrast, rectal biopsies for cell densities of somatostatin and peptide YY showed high sensitivity and specificity for irritable bowel syndrome ranging 80-90%., Conclusion: Enzyme-linked immunosorbent assay testing for anti-cytolethal distending toxin B and anti-vinculin as well as rectal biopsies for cell densities could be potential diagnostic tests for irritable bowel syndrome.

Objectives: Paediatric and adult inflammatory bowel disease (pIBD, aIBD) patients may lose response to anti-tumour necrosis factor (TNF) treatment within the first year. Adult-extrapolated weight-based dosing is incorrect in children, due to age-related pharmacokinetic differences. We investigated biomarkers for initial and maintenance of response to infliximab (IFX) or adalimumab (ADA), comparing pIBD and aIBD patients., Methods: In this prospective, observational study, pIBD (n = 24) and aIBD (n = 21) patients were included when initiating anti-TNF. Escalation from standard dosing and continued anti-TNF at 12 and 18 months were assessed. Biomarkers included clinical laboratory parameters, faecal calprotectin (FCP) and IFX trough levels (TLs). Plasma proteomics was performed in pIBD., Results: During our study, treatment escalation (in clinical loss of response) occurred more common in pIBD versus aIBD (p = 0.02). We established that IFX therapy escalation in pIBD patients was not due to low infliximab levels. We identified 9 pro-inflammatory proteins that were elevated in patients losing response., Conclusion: Anti-TNF exposure-response relationship may be different in pIBD versus aIBD. No biomarkers for maintained response were identified, but 9 inflammatory proteins were of interest as potential predictors for loss of response in pIBD., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Gut dysbiosis and increased intestinal permeability have been reported to precede type 1 diabetes-related autoimmunity. The role of gut inflammation in autoimmunity is not understood., Objectives: This study aimed to assess whether gut inflammation markers are associated with risk of islet autoimmunity and whether diet is associated with gut inflammation markers., Methods: A nested case-control sample of 75 case children with islet autoimmunity and 88 control children was acquired from the Finnish Type 1 Diabetes Prediction and Prevention cohort. Diet was assessed with 3-d food records, and calprotectin and human β-defensin-2 (HBD-2) were analyzed from stool samples at 6 and 12 mo of age. Conditional logistic regression analysis was used in a matched case-control setting to assess risk of autoimmunity. Analysis of variance, independent samples t test, and a general linear model were used in secondary analyses to test associations of background characteristics and dietary factors with inflammation markers., Results: In unadjusted analyses, calprotectin was not associated with risk of islet autoimmunity, whereas HBD-2 in the middle (odds ratio [OR]: 3.23; 95% confidence interval [CI]: 1.03, 10.08) or highest tertile (OR: 3.02; 95% CI: 1.05, 8.69) in comparison to the lowest at 12 mo of age showed borderline association (P-trend = 0.063) with higher risk of islet autoimmunity. Excluding children with cow milk allergy in sensitivity analyses strengthened the association of HBD-2 with islet autoimmunity, whereas adjusting for dietary factors and maternal education weakened it. At age 12 mo, higher fat intake was associated with higher HBD-2 (β: 0.219; 95% CI: 0.110, 0.328) and higher intake of dietary fiber (β: -0.294; 95% CI: -0.510, -0.078), magnesium (β: -0.036; 95% CI: -0.059, -0.014), and potassium (β: -0.003; 95% CI: -0.005, -0.001) with lower HBD-2., Conclusions: Higher HBD-2 in infancy may be associated with higher risk of islet autoimmunity. Dietary factors play a role in gut inflammatory status., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pharmacokinetic non-inferiority of subcutaneous (SC) to intravenous (IV) CT-P13 maintenance therapy was demonstrated in a randomized trial (NCT02883452). This post hoc analysis evaluated longitudinal clinical outcomes with the two infliximab treatment strategies., Methods: Patients with Crohn's disease or ulcerative colitis received CT‑P13 IV loading doses (5 mg/kg; Week [W] 0 and W2) before randomization (1:1) to receive CT-P13 SC (body weight-based dosing every 2 weeks [Q2W]; W6-54; 'SC maintenance group') or CT‑P13 IV (5 mg/kg Q8W; W6-22) then CT-P13 SC (Q2W; W30-54; 'IV-to-SC switch group'). Paired W30/W54 patient-level data were analyzed., Results: Fifty-three (IV-to-SC switch) and fifty-nine (SC maintenance) patients were analyzed. Median trough serum CT-P13 concentrations were significantly higher at W54 versus W30 in the IV-to-SC switch group (20.4 versus 2.3 µg/mL; p < 0.00001), while remaining consistent in the SC maintenance group. Statistically significant improvements in pharmacokinetics, efficacy, fecal calprotectin levels, and quality of life were seen following switch to SC administration at W30 in the IV-to-SC switch group; safety findings were similar pre- and post-switch., Conclusion: Formulation switching from IV to SC infliximab maintenance therapy was well tolerated and may provide additional clinical improvements. Findings require confirmation in larger prospective studies., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The serum-based endoscopic healing index (EHI) test identifies endoscopic Crohn's disease (CD) activity. Data are lacking on the relationship between EHI with other endpoints. We assessed the relationship between EHI and the simplified Magnetic Resonance Index of Activity., Materials and Methods: Data were prospectively collected on patients with CD with either an EHI or fecal calprotectin (FCAL) within 90 days of magnetic resonance enterography (MRE). Diagnostic accuracy was assessed using area under the receiver operator characteristics. Proportions with any, severe, and terminal ileum MR inflammation were compared above/below identified thresholds for both EHI and FCAL., Results: A total of 241 MREs paired to either EHI or FCAL from 155 patients were included. Both EHI and FCAL had similar accuracy to diagnose inflammation (area under the receiver operator characteristics: EHI: 0.635 to 0.651, FCAL: 0.680 to 0.708). Optimal EHI values were 42 and 26 for inflammation on MRE and endoscopy, respectively. Patients with EHI ≥42 (100% vs. 63%, P =0.002), FCAL >50 µg/g (87% vs. 64%, P <0.001) and FCAL >250 µg/g (90% vs. 75%, P =0.02) had higher rates of simplified Magnetic Resonance Index of Activity ≥1 compared with lower values. EHI differentiated ileitis numerically more than FCAL (delta: 24% to 25% vs. 11% to 21%). Patients with FCAL ≥50 µg/g had higher rates of severe inflammation compared with FCAL <50 µg/g (75% vs. 47%, P <0.001), whereas smaller differentiation existed for EHI threshold of 42 (63% vs. 49%, P =0.35)., Conclusion: Both EHI and FCAL were specific in their confirmation of inflammation and disease activity on MRE in patients with CD. However, MRE-detected inflammation was frequently present in the presence of low EHI and FCAL in similar proportions., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition. While inflammatory biomarkers are valuable for diagnosing and monitoring the disease, their correlation with patients' quality of life (QoL) is not well-established., Purpose: This study aims to investigate the correlations between inflammatory biomarkers and the quality of life (QoL) variables of individuals diagnosed with IBD in clinical remission., Methods: The sample of this cross-sectional study included 74 patients (80% women; 45 ± 11 years old) diagnosed with IBD. Outcome variables included faecal calprotectin (FC), C-reactive protein (CRP), cortisol levels from hair samples, and anxiety and depression assessed using the Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively), alongside QoL evaluated with the Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32). Bivariate correlations were calculated using the Pearson correlation coefficient, and stepwise linear regression analyses were conducted to identify independent factors contributing to IBDQ-32 scores., Results: The IBDQ-32 did not significantly correlate with any biomarkers. However, it exhibited a large and statistically significant negative correlation with HADS-A (r = -0.651) and HADS-D (r = -0.611) scores ( p  < 0.001). Stepwise linear regression analyses indicated that HADS-A was a significant and independent predictor for IBDQ-32 scores (Adjusted R 2 = 0.41, β = -0.65, p  < 0.001)., Conclusions: Inflammatory markers such as CRP, FC, or cortisol in hair do not play a decisive role in assessing the QoL of IBD patients. These findings emphasize the significance of considering psychological factors in evaluating and managing QoL in IBD patients in order to identify severity, suggesting that instruments like HADS should be integral to comprehensive patient assessments.

Introduction: A large proportion of patients with inflammatory bowel disease (IBD) experience IBD-related inflammatory conditions outside of the gastrointestinal tract, termed extraintestinal manifestations (EIMs) which further decreases quality of life and, in extreme cases, can be life threatening. The pathogenesis of EIMs remains unknown, and although gut microbiota alterations are a well-known characteristic of patients with IBD, its relationship with EIMs remains sparsely investigated. This study aimed to compare the gut microbiota of patients with IBD with and without EIMs., Methods: A total of 131 Danish patients with IBD were included in the study, of whom 86 had a history of EIMs (IBD-EIM) and 45 did not (IBD-C). Stool samples underwent 16S rRNA sequencing. Amplicon sequence variants (ASVs) were mapped to the Silva database. Diversity indices and distance matrices were compared between IBD-EIM and IBD-C. Differentially abundant ASVs were identified using a custom multiple model statistical analysis approach, and modules of co-associated bacteria were identified using sparse correlations for compositional data (SparCC) and related to patient EIM status., Results: Patients with IBD and EIMs exhibited increased disease activity, body mass index, increased fecal calprotectin levels and circulating monocytes and neutrophils. Microbiologically, IBD-EIM exhibited lower fecal microbial diversity than IBD-C (Mann-Whitney's test, p  = .01) and distinct fecal microbiota composition (permutational multivariate analysis of variance; weighted UniFrac, R 2  = 0.018, p  = .01). A total of 26 ASVs exhibited differential relative abundances between IBD-EIM and IBD-C, including decreased Agathobacter and Blautia and increased Eggerthella lenta in the IBD-EIM group. SparCC analysis identified 27 bacterial co-association modules, three of which were negatively related to EIM (logistic regression, p  < .05) and included important health-associated bacteria, such as Agathobacter and Faecalibacterium ., Conclusions: The fecal microbiota in IBD patients with EIMs is distinct from that in IBD patients without EIM and could be important for EIM pathogenesis.

Background and Aims: Recent research has shown that Western-style diets have been associated with an increased risk of inflammatory bowel diseases (IBD). Our aim was to examine the link between an anti-inflammatory diet and the maintenance of IBD remission, as well as to assess the potential therapeutic advantages of this dietary approach in preserving IBD remission., Methods: The inclusion and exclusion criteria were applied to a total of 189 individuals with IBD, with 21 individuals not meeting the criteria. Therefore, 168 eligible patients were enrolled in the study and allocated to either an anti-inflammatory diet or a regular diet, based on their personal preference., Results: A cohort of 168 IBD adult patients was recruited for the study: 88 patients with ulcerative colitis and 80 with Crohn's disease. The intervention group received an anti-inflammatory diet consisting of the removal of red and processed meat, fried foods, high-lactose foods, fast food, white bread, sugar, and vegetable oils rich in omega-6 for a period of 1 year. The clinical response was maintained in 80 patients (95.2%) in the intervention group and in 72 patients (85.7%) in the control group (p-value=0.036). Although not statistically significant, fecal calprotectin was higher in the control group than in the intervention group at follow-up., Conclusions: Patients who adhered to an anti-inflammatory diet exhibited a higher rate of maintenance of clinical remission. Furthermore, improvement in inflammation tests was observed in the intervention group, reinforcing the proposition that IBD is a lifestyle-related disease.

Objectives: The purpose of this prospective cohort study is to evaluate the effect of peri-implant phenotype (PPh) on the severity of peri-implant diseases and the results of non-surgical mechanical treatment (NSMT), along with calprotectin (CLP) and MMP-8(matrix metalloproteinase-8) levels., Materials and Methods: 77 implants from 39 patients were included. The implants were categorized Group-1(peri-implant mucositis), Group-2(peri-implantitis).Baseline (0. Month-PrT) clinical parameters (PD, GI, PI, BOP, CAL) and radiographic bone loss were documented, and peri-implant crevicular fluid (PICF) samples were collected. Various intruments and methodologies were employed to assess PPh components (mucosa thickness, supracrestal tissue height, keratinized mucosa) and peri-implant attached mucosa (AM). NSMT was applied to diseased implant sites. All clinical parameters were reassessed again by taking PICF samples at the 6th month-after treatment (PT). In PICF samples obtained from both groups, MMP-8 and CLP levels were evaluated using the ELISA test., Results: PrT-PD,PrT-GI,PrT-CAL and PrT-BOP percentage values in Group-2 were significantly higher than Group-1.PrT-PD,PrTPI scores are significantly higher in thin biotype implants. All components of the PPh and AM were significantly lower in thin biotype. Intra-group time-dependent changes of MMP-8 and CLP were significant in both groups (p < 0.05). When the relationship between thin and thick biotype and biochemical parameters was evaluated, the change in PrT-PT didn't show a significant difference (p > 0.05)., Conclusions: PPh plays a role in influencing the severity of peri-implant diseases. However, the impact of phenotype on NSMT outcomes was similar in both groups., Clinical Relevance: The PPh should be considered when planning implant surgery., (© 2024. The Author(s).)

Calprotectin, a metal ion-binding protein complex, plays a crucial role in the innate immune system and has gained prominence as a biomarker for various intestinal and systemic inflammatory and infectious diseases, including inflammatory bowel disease (IBD) and tuberculosis (TB). Current clinical testing methods rely on enzyme-linked immunosorbent assays (ELISAs), limiting accessibility and convenience. In this study, we introduce the Fab-Enabled Split-luciferase Calprotectin Assay (FESCA), a novel quantitative method for calprotectin measurement. FESCA utilizes two new fragment antigen binding proteins (Fabs), CP16 and CP17, that bind to different epitopes of the calprotectin complex. These Fabs are fused with split NanoLuc luciferase fragments, enabling the reconstitution of active luciferase upon binding to calprotectin either in solution or in varied immobilized assay formats. FESCA's output luminescence can be measured with standard laboratory equipment as well as consumer-grade cell phone cameras. FESCA can detect physiologically relevant calprotectin levels across various sample types, including serum, plasma, and whole blood. Notably, FESCA can detect abnormally elevated native calprotectin from TB patients. In summary, FESCA presents a convenient, low-cost, and quantitative method for assessing calprotectin levels in various biological samples, with the potential to improve the diagnosis and monitoring of inflammatory diseases, especially in at-home or point-of-care settings.

Objective: Intestinal inflammation with contradictory data on faecal calprotectin (fCP) levels is documented in patients with cystic fibrosis (CF). The aim of this study was to longitudinally evaluate fCP in a cohort of children with CF and their relationship with clinical variables., Design: Prospective observational study to assess evolution of fCP levels, primary aimed at improving fat absorption. Along 1.5 years of follow-up (November 2016-May 2018) with four study visits pertaining to a pilot study (two of four) and to a clinical trial (two of four), the study outcomes were measured., Setting: Six European CF centres in the context of MyCyFAPP Project., Subjects: Children with CF and pancreatic insufficiency (2-18 years old)., Main Outcome Measurements: fCP levels, pulmonary function (percentage of forced expiratory volume in 1 s (FEV 1 %)) and coefficient of fat absorption (CFA). Additionally, in the last two visits, gastrointestinal (GI) symptoms were evaluated through the PedsQL-GI Questionnaire. Linear mixed regression models were applied to assess association between fCP and FEV 1 , CFA and GI symptoms., Results: Twenty-nine children with CF and pancreatic insufficiency were included. fCP levels were inversely associated with total modified specific PedsQL-GI score (p=0.04) and positively associated with diarrhoea (p=0.03), but not with CFA. Along the four study visits, fCP significantly increased (from 62 to 256 µg/g) and pulmonary function decreased (from 97% to 87%), with a significant inverse association between the two study outcomes (p<0.001)., Conclusions: In children with CF, fCP levels are inversely associated with pulmonary function and thus the specificity of fCP as a marker of intestinal inflammation in paediatric patients with CF warrants further investigation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)