Pediatric Crohn's Disease Activity Index Research Articles

Methanogenic Archaea in the Pediatric Inflammatory Bowel Disease in Relation to Disease Type and Activity.

The inflammatory bowel disease (IBD) is associated with gut microbiota dysbiosis; however, studies on methanogens-especially those focused on children-are extremely limited. The aim of this study was to determine the abundance of total methanogenic archaea and their three subgroups: Methanobrevibacter (Mb.) smithii, Methanosphaera (Ms.) stadtmanae, and Methanomassiliicoccales, in the feces of children with both active and inactive Crohn's disease (CD) and ulcerative colitis (UC). The results of a quantitative real-time PCR were cross-referenced with the disease type (CD vs. UC) and activity assessed with the use of Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI) indices, and fecal calprotectin (FCP) concentration, and compared with controls. There was a significant decrease in the number of total methanogens in CD and UC compared to controls. The prevalence of total methanogens was also lower in UC compared to controls. Furthermore, patients from the inactive UC group were colonized by a lower number of Mb. smithii, and demonstrated the most pronounced positive correlation between the number of Ms. stadtmanae and the FCP concentration. Our results demonstrate that gut methanogens are related to the type and activity of pediatric IBD.

Single-center Experience With Upadacitinib for Adolescents With Refractory Inflammatory Bowel Disease.

Upadacitinib (UPA) is a novel selective JAK inhibitor approved for adults with ulcerative colitis (UC) and with positive phase 3 data for Crohn's disease (CD). Pediatric off-label use is common due to delays in pediatric approvals; real-world data on UPA are needed to understand the safety and effectiveness in pediatric IBD. This is a single-center retrospective case series study of adolescents (12-17 years) with inflammatory bowel disease IBD on UPA. The primary outcome was postinduction steroid-free clinical remission (SF-CR) defined as Pediatric UC Activity Index (PUCAI) or Pediatric CD Activity Index (PCDAI) ≤10. Secondary outcomes include postinduction clinical response (decrease ≥12.5 in PUCAI/PCDAI), postinduction C-reactive protein (CRP) normalization, 6-month SF-CR, and intestinal ultrasound response and remission. Adverse events were recorded through last follow-up. Twenty patients (9 CD, 10 UC, 1 IBD-U; 55% female; median age 15 years, 90% ≥2 biologics) were treated with UPA for ≥12 weeks (median 51 [43-63] weeks). Upadacitinib was used as monotherapy in 55% and as combination with ustekinumab and vedolizumab in 35% and 10%, respectively. Week 12 SF-CR was achieved in 75% (15/20) and 80% (16/20) with CRP normalization. About 3/4 (14/19) achieved SF-CR at 6 months. Adverse event occurred in 2 patients (10%): Cytomegaloviruscolitis requiring hospitalization and hyperlipidemia requiring no treatment. In the 75% with ultrasound monitoring, response and remission were achieved in 77% and 60%, respectively. While awaiting pediatric registration trials, our data suggest that UPA is effective in inducing and maintaining SF-CR in adolescents with highly-refractory IBD with an acceptable safety profile.

Intestinal ultrasound score predicts therapeutic outcomes of infliximab in pediatric patients with Crohn’s disease

Background and aims Objective evaluation of treatment response is critical in the management of Crohn’s disease (CD). Compared with endoscopy, intestinal ultrasound (IUS) is non-invasive and well-tolerated. This study is aimed to assess the predictive value of IUS score for treatment response in pediatric CD patients. Methods We conducted a retrospective study in pediatric CD patients who underwent endoscopy and IUS at start of infliximab treatment [T0] and after 22–38 weeks [T1] between February 2021 and January 2023. Pediatric Crohn’s Disease Activity Index (PCDAI), biochemical parameters, the Simple Endoscopic Score for Crohn’s disease (SES-CD) and IUS parameters were collected at two timepoints. IUS scores were assessed by International Bowel Ultrasound Segment Activity Score (IBUS-SAS). Results Thirty patients were included, with 53.3% reaching endoscopic response and 43.3% endoscopic remission. After infliximab treatment, IBUS-SAS (58.5 ± 24.2 vs 34.4 ± 21.6, p = .0001) was significantly decreased. At T1, change in IBUS-SAS (−38.2 ± 22.0 vs −7.9 ± 24.1, p = .0015) were pronounced in patients with endoscopic response compared with endoscopic non-response. Significant correlation were observed between IBUS-SAS and SES-CD, PCDAI, C-reaction protein, erythrocyte sedimentation rate, hemoglobin, albumin. The most accurate cutoff values for predicting endoscopic response were 57.4% decrease of IBUS-SAS (AUROC: 0.862, p < .001). The optimal cut-off of IBUS-SAS to correlate endoscopic remission was 26.0 (AUROC: 0.686, p = .017). Conclusions The validated ultrasound-base score, IBUS-SAS is an effective index for monitoring endoscopic response to infliximab therapy in CD. IUS evaluation could guide treatment decision for pediatric CD.

Relationship between disease activity index and sleep disorders in children with inflammatory bowel diseases.

The aim of the study was to assess the prevalence of sleep disturbance in pediatric IBD patients and evaluate the relationship between clinical features of IBD, disease activity, inflammatory markers and quality of sleep. A total of 99 patients who were followed-up with the diagnosis of IBD (44 Crohn's disease (CD), 55 Ulcerative colitis (UC)) between 2015-2020 and 80 healthy controls were enrolled in the study. The clinical and demographic characteristics, laboratory parameters and disease activities were obtained from medical reports retrospectively. Pittsburgh sleep quality index (PSQI) was administered to all participants. PSQI score was significantly higher in patient group than the control group (P < 0.001). The sleep time of patient group, especially patients with UC was later than the control group (P = 0.008). Sleep duration was longer in control group than the patient group (P < 0.001). A positive strong correlation was obtained in disease activity index (r = 0.886; P < 0.001) and abdominal pain (r = 0.781; P < 0.001) with PSQI scores of CD patients. Disease activity index, rectal bleeding, diarrhea and number of stool had statistically significant positive strong correlation with PSQI scores of UC patients (P < 0.001). Pediatric Crohn's disease activity index and Pediatric ulcerative colitis activity index were the only independent risk factors affecting sleep disturbances (80% sensitivity and 91.67% specificity, 93.1% sensitivity and %96.15 specificity, respectively). Conclusion: Increased disease activity has adverse effects on sleep quality. PSQI and PCDAI were strong tests for predicting sleep disorders in pediatric patients with IBD. What is Known: •Sleep disturbances are common complaint in inflammatory bowel disease (IBD), even in clinical remission. •Pittsburgh sleep quality index (PSQI) was used to evaluate the subjective sleep quality of patients. What is New: •PSQI and Pediatric Crohn Disease Activity index (PCDAI) were strong tests for predicting sleep disorders in pediatric patients with IBD. •PSQI and PCDAI scores correlated significantly with the severity of the sleep disturbances.

Can We Rely on Resting Metabolic Rate Equations? Large Variance in Crohn Disease Pediatric Patients.

Inadequate caloric intake is common in Crohn disease (CD) and nutrition support plays an important role in remission induction and in meeting nutritional needs. For nutritional planning, determining resting metabolic rate (RMR) is essential in pediatric patients with CD. To measure RMR in CD pediatric patients using indirect calorimetry, and compare it with estimated RMR (eRMR) calculated by Schofield equation. Children with CD treated in a tertiary pediatric inflammatory bowel disease center in Israel participated in the cross-sectional study. At study visits, weight, height, clinical and laboratory assessments, bioelectrical impedance, and RMR measured by indirect calorimetry were done. Additionally, disease severity was determined by the Pediatric Crohn Disease Activity Index and eRMR was calculated using the Schofield equation. The ratio of the measured RMR to eRMR was performed in addition to the Spearman correlation test. The study group included 73 children (49 boys) with mean age of 13.9 ± 2.3 years. Children with moderate or severe disease had lower weight for age z score, lower BMI- z , and lower RMR compared to children with mild disease. However, when RMR was adjusted for fat free mass (n = 50), the association between RMR and disease severity disappeared. Variance in RMR was high between subjects. Our data suggest that the Schofield equation is inadequate for determining RMR in pediatric CD and that RMR should be measured to guarantee the most appropriate nutritional intervention.

Comparison of Clinical Outcomes in Pediatric Patients with Ileocolonic Crohn Disease Treated with Infliximab Versus Adalimumab.

Infliximab is considered superior to adalimumab in patients with ulcerative colitis, especially in severe cases. Whether this is true for Crohn disease (CD) patients with colonic involvement is unclear. Our aim was to compare the clinical effectiveness of infliximab versus adalimumab in pediatric ileocolonic (L3) CD. This retrospective study included patients <18 years with ileocolonic CD treated with infliximab or adalimumab between 2014 and 2021. Primary outcome was steroid-free clinical remission by week 52. Secondary outcomes were treatment modifications, drug discontinuation, inflammatory bowel disease (IBD)-associated hospitalizations, and surgery during the first year of treatment. We identified 74 patients treated with adalimumab and 41 with infliximab, with comparable demographic features. Concomitant immunomodulator therapy at biologic initiation was significantly lower in the adalimumab group (28% vs 85%, P < 0.001). Rates of drug intensification were higher in the infliximab group at end of induction (EOI) and at 52 weeks (55% vs 32% and 88% vs 46%, P < 0.001). Given significant differences between initial median Pediatric Crohn Disease Activity Index scores (20.0 [interquartile range, IQR 15.0-27.5] vs 11.0 [IQR 7.5-20.0] for infliximab and adalimumab groups, respectively, P < 0.001), propensity score matching was performed. Following matching, the rate of patients in steroid-free clinical remission by EOI was significantly higher in the adalimumab group (93.8% vs 46.9%, P < 0.001), but comparable by 1 year. Moreover, inflammatory markers and fecal calprotectin values were also similar at these time points. Rates of drug discontinuation, IBD-associated admissions, and surgery were similar between groups. In a retrospective study of patients with ileocolonic CD, adalimumab and infliximab had comparable outcomes by 52 weeks.

The effectiveness of two-stage surgical treatment of children with complicated Crohn’s disease

Introduction. Crohn’s disease (CD) is an inflammatory disease of the digestive tract of unknown etiology with segmental transmural inflammation of various parts of the gastrointestinal tract. The annual increase in the number of children with newly diagnosed CD, late diagnosis and untimely surgical treatment is one of the urgent problems due to the lack of a single algorithm of surgical treatment.&#x0D; The aim: to determine the effectiveness of surgical treatment of CD in children.&#x0D; Materials and methods. The study included thirty six patients with complicated CD Over the period from 2018 to 2022, a re­trospective and prospective analysis of children who received medical care for CD with two-stage surgical treatment (resection of the affected area with enterostomy and subsequent restoration of gastrointestinal continuity) was carried out. &#x0D; Results. Clinical activity according to Pediatric Crohn’s Disease Activity Index (PCDAI) in 23 (63.8%) children before treatment was recorded as high (30.0–75.2 points), in 15 (36.2%) children had average activity (11–29 points). After the staged surgical treatment, there was a change in the indicators — the onset of remission in 2 (5.5%) children and in 34 (94.5%) mild course &#x0D; (p &lt; 0.05). Statistical analysis of anthropometric indicators revealed positive changes (HAZ p &lt; 0.05 and BAZ p &lt; 0.001) with increase in weight and height criteria. Assessment of laboratory dynamics revealed positive changes (p &lt; 0.001) — the absence of anemia, hypoalbuminemia and relief of bacterial inflammation. CD debuted before the age of 10 years in 7 children (19.4%), aged 10 to 16 years — in 29 (80.5%). In 24 (66.7%) children, genetic engineering biological therapy (GEBT) at the time of the development of surgical complications was not performed, from them 15 (62.5%) received hormonal and immunomodulatory therapy while it was not effective, while for 9 (37.5%) patients the timely verification was diagnosed at the stage of development of CD complications. However, the development of surgical complications was noted in 12 (33.3%) children, despite the timely verification and appointment of treatment for genetic engineering biologic therapy (GEBT). Biological therapy was continued for 7 (58.3%) children who received GEBT before surgery, and in 5 (41.7%) patients, treatment was continued with a change of GEBT. The period of stay with a stoma was found to be from 7 to 31 months (Me = 8).&#x0D; Conclusions. In complicated forms of CD in children, despite drug therapy, including GEBT, the development of complications requiring surgical treatment was noted, which indicates an aggressive and progressive course of CD. However, the use of stage-by-stage surgical treatment showed efficiency due to the positive dynamics of anthropometric indicators, laboratory markers, the potency of surgical treatment, and made it possible to achieve stable remission against the background of specific therapy and improve the quality of life in CD children.

Changes in the gut mycobiome in pediatric patients in relation to the clinical activity of Crohn's disease

Numerous studies have shown that in Crohn's disease (CD), the gut microbiota is of great importance in the induction and maintenance of inflammation in the gastrointestinal tract. Until recently, studies have focused almost exclusively on bacteria in the gut. Lately, more attention has been paid to the role of intestinal fungi. To study the gut mycobiome analysis of pediatric patients with CD (in different stages of disease activity) compared to healthy children. Fecal samples were collected from patients: With active, newly diagnosed CD (n = 50); active but previously diagnosed and treated CD (n = 16); non-active CD and who were in clinical remission (n = 39) and from healthy volunteers (n = 40). Fungal DNA was isolated from the samples. Next, next generation sequencing (MiSeq, Illumina) was performed. The composition of mycobiota was correlated with clinical and blood parameters. Candida spp. were overrepresented in CD patients, while in the control group, the most abundant genus was Saccharomyces. In CD patients, the percentage of Malassezia was almost twice that of the control (P < 0.05). In active CD patients, we documented a higher abundance of Debaryomyces hansenii (D. hansenii) compared to the non-active CD and control (P < 0.05) groups. Moreover, statistically significant changes in the abundance of Mycosphaerella, Rhodotorula, and Microidium were observed. The analyses at the species level and linear discriminant analysis showed that in each group it was possible to distinguish a specific species characteristic of a given patient population. Moreover, we have documented statistically significant correlations between: D. hansenii and patient age (negative); C. zeylanoides and patient age (positive); C. dubliniensis and calprotectin (positive); C. sake and calprotectin (positive); and C. tropicalis and pediatric CD activity index (PCDAI) (positive). Mycobiome changes in CD patients, and the positive correlation of some species with calprotectin or PCDAI, give strong evidence that fungi may be of key importance in the development of CD.

P716 A 2-week course of Exclusive Enteral Nutrition followed by the Crohn Disease Exclusion Diet is effective for Induction and Maintenance of Remission in children with Crohn Disease; the DIETOMICS-CD trial

Abstract Background Exclusive enteral Nutrition (EEN) is considered a first line therapy for children with active Crohn disease (CD). CD Exclusion Diet (CDED)+Partial Enteral Nutrition (PEN) is effective for induction of remission in mild-moderate CD at weeks 6 and 12, with better tolerance than EEN. We assessed whether a 2-week course of EEN, followed by CDED+PEN is superior to 8 weeks of EEN in sustaining clinical remission at week 14, outcomes of CDED up to 24 weeks, and the utility of CDED in mild-severe CD. Methods This international, multicenter, randomized-controlled trial compared 2 weeks of EEN (Modulen, Nestle Health Science) followed by 3 phases of the CDED+PEN to 8 weeks of EEN, followed by PEN with free diet, both up to week 24. Children aged 8-18 with CD&amp;lt;3 years, mild-severe disease [paediatric CD activity index (PCDAI) 15-47.5], and active inflammation [elevated C-reactive protein (CRP) or faecal calprotectin (FCP)] were included. Stable immunomodulator (IM) treatment was allowed. Naïve patients were allowed to start an IM from week 4. Results Of the 63 eligible patients enrolled, 55 were randomized and included in the final intention to treat analysis (target recruitment failed due to COVID); Group 1 (CDED+PEN;29) and group 2 (EEN;26), mean age 12.7±2.4. Steroids-free sustained remission at week 14 was obtained in 20/29(69%) in group 1 and 16/26(61.5%) in group 2, p=0.56. Remission at week 8 was obtained in 22/29(76%) in group 1 and 14/26(54%) in group 2, p=0.08. 16/29(55%) in group 1 and 9/26(34%) in group 2 maintained clinical remission at week 24; p=0.12. Median PCDAI declined from 32.5[20-36.2] to 2.5[0-5.6] and 1.2[0-5.6] in group 1 (p&amp;lt;0.001 for all), and from 22.5[20-29.3] to 0[0-4.3] and 0[0-2.5] in group 2 (p&amp;lt;0.005 for all) at baseline, week 8 and 14 respectively. Median CRP improved in group 1 from 32 mg/L[6-69] to 5[2-16] and 3[2-10.1] (p&amp;lt;0.001 for both) and in group 2 from 10.35 mg/L[5-33] to 3.7[2.2-7.2], p=0.012 and 3.2[2.8-5], p=0.006 at baseline, week 8 and 14 respectively. Median FCP declined in group 1 from 1946 µg/g [862-3304] to 802[196-1312] at week 8 and 241[82-1175] at week 14 (p&amp;lt;0.01 for both), and in group 2 from 1615[605-2692] at baseline to 436[252-1389] at week 8, which then increased to 731[349-1305] at week 14 (p&amp;lt;0.01 for both). At week 14, 12/22(54%) received IM from group 1 and 15/16(93%) from group 2; p= 0.009. Conclusion Two weeks of EEN followed by CDED&amp;PEN and EEN were successful in induction of clinical and biochemical remission in mild-severe paediatric CD, and most CDED+PEN patients-maintained remission to 24 weeks. Sustained clinical remission at week 14 was similar despite higher IM use in the EEN Group, suggesting that CDED might prevents diet-induced inflammation regardless of IM use.

P223 The usefulness of tissue calprotectin in pediatric Crohn’s disease – a pilot study.

Abstract Background Fecal calprotectin (FCP) is a highly sensitive biomarker of intestinal inflammation widely used in diagnostics and monitoring of inflammatory bowel disease (IBD). However, it cannot be used to localize the disease activity and its levels may be false negative or false positive in some cases. The aim of this study was to evaluate tissue calprotectin (TCP) in pediatric patients with Crohn’s disease (CD) and correlate it with FCP and clinical activity of the disease. Methods Fifty-seven pediatric patients with CD at the median age of 10.5 (1-17) years (yrs) were examined for fecal and tissue calaprotectin. Values were correlated to disease activity and histopathological changes of the patients’ endoscopic biopsies. Disease activity was assessed using Pediatric Crohn’s Disease Activity Index (PCDAI), fecal calprotectin (FCP) was measured with ELISA test and the immunohistochemical (IHC) staining for calprotectin antigen was performed on bioptic samples from 6 bowel segments and the number of TCP cells was counted per high power field (HPF). Non-parametric statistical tests were used for data analysis. Results Patients’ median PCDAI score was 10 (0-63.5), while median FCP was 535 (30-600) ug/g. The only observed correlation was between FCP level and disease activity. There was no associated neither between FCP and TCP, nor TCP and PCDAI. Conclusion Tissue calprotectin unlike FCP does not seem to be a good predictor of disease activity in Polish pediatric patients with CD.

The Usefulness of Tissue Calprotectin in Pediatric Crohn’s Disease—A Pilot Study

Background: Fecal calprotectin (FCP) is a highly sensitive biomarker of intestinal inflammation widely used in diagnostics and monitoring of inflammatory bowel disease (IBD). Immunohistochemical assessment of calprotectin in the bowel mucosa is not a diagnostic standard. Therefore, the aim of this study was to evaluate tissue calprotectin (TCP) as a potential marker providing added insight for pediatric patients with Crohn’s disease (CD). Methods: Fecal and tissue calprotectin were measured in children with CD. The values were correlated with disease activity and histopathological changes of the patients’ endoscopic biopsies. Disease activity was assessed using the Pediatric Crohn’s Disease Activity Index (PCDAI); fecal calprotectin (FCP) was measured with the ELISA test. Immunohistochemical (IHC) staining for calprotectin antigen was performed on the biopsy samples from six bowel segments, and the number of TCP cells was counted per high power field (HPF). Non-parametric statistical tests were used for data analysis. Results: Fifty-seven children with CD with a median age of 10.5 (1–17) years (yrs) were examined for fecal and tissue calprotectin. The patients’ median PCDAI score was 10 (0–63.5), while median FCP was 535 (30–600) μg/g. We observed a correlation between disease activity (PCDAI) and FCP, TCP in inflammatory lesions and in crypts. There was no association either between FCP and TCP or between TCP in epithelium and PCDAI. Conclusion: It seems that IHC detection of calprotectin in bowel mucosa to assess disease behavior may be useful. FCP is a gold-standard biomarker in the diagnosis, monitoring and prognosis of IBD, and its levels correlated well with clinical activity in our study group.

The impact of exclusive enteral nutrition on the gut microbiome and bile acid metabolism in pediatric Crohn's disease

Gut dysbiosis and associated bile acid (BA) metabolism play an important role in the pathogenesis of Crohn's disease (CD). We investigated the impacts of the exclusive enteral nutrition treatment (EEN) on the gut microbiome (GM) and BAs metabolism for patients with CD. Targeted metabolomics analysis and metagenomics analysis were performed in feces to investigate the BA and GM changes of patients before and after 2-months EEN therapy. The Pediatric Crohn's Disease Activity Index (PCDAI) and fecal calprotectin were used to evaluate the severity and mucosal inflammation of CD. A total of 27 newly diagnosed pediatric patients with CD and 27 healthy controls were recruited in this study. Both GM structure and the secondary BA metabolism were significantly impaired in patients, which could return towards normal levels after EEN treatment. The most abundant taxa Firmicutes and 11 BAs were found closely associated with the PCDAI score and fecal calprotectin. Meanwhile, the close interactions between Firmicute bacteria and BAs might contribute to the remission of CD after EEN treatment. The qPCR data further confirmed that the relative expressions of Firmicutes phylum, and genus Flavonifractor and Clostridium V were improved after EEN treatment. Firmicutes bacteria and the balance of primary and secondary BA compositions in the gut were closely associated with the health status of CD disease indicated by the PCDAI score and fecal calprotectin. Understanding the recovery process of gut microbiome and BA metabolism will help us to explore the potential mechanisms of EEN therapy.

Fecal calprotectin in predicting small bowel capsule endoscopy findings in pediatric patients with known Crohn's disease.

Fecal calprotectin (FC) has been proposed as a noninvasive surrogate marker of intestinal inflammation in inflammatory bowel disease. This study aimed to assess the capability of FC in predicting small bowel capsule endoscopy (SBCE) findings in pediatric patients with known Crohn’s disease (CD). We retrieved data of consecutive patients aged 2 to 17 years old with established CD who underwent SBCE from Janurary 2017 to April 2020 and had endoscopic remission on ileocolonoscopy. Sixty-eight patients were included in the analysis. There were 13 patients with a weighted pediatric CD activity index ≥ 12.5, 47 patients with FC ≥ 200 µg/g, and 45 patients with significant small bowel (SB) inflammation [Lewis score (LS) ≥ 135]. The LS correlated weakly with FC (R = 0.30, P < .05). The area under the curve of FC as a surrogate diagnostic test for LS ≥ 135 was 0.691, and the optimal FC cutoff values were 242 µg/g with the corresponding sensitivity and specificity of 78% and 65%, respectively. The area under the curve of FC for moderate-to-severe inflammatory activity in the SB was 0.718. In patients with FC level ≥ 670 µg/g, LS ≥ 790 was found in 33% (9/27) of patients, with the sensitivity and specificity of 69% and 67%, respectively. FC may be used to predict SB mucosal inflammation in pediatric patients with confirmed CD having endoscopic remission on ileocolonoscopy.

The Simplified MR Index of Activity Score in Pediatric Small-Bowel Crohn Disease: An Interreader Agreement and Responsiveness Study.

BACKGROUND. The simplified MR index of activity (MaRIA) score is used to assess the severity of small-bowel inflammation without use of IV contrast material. OBJECTIVE. The purposes of this study were to assess interreader agreement on the use of simplified MaRIA scores for evaluation of the inflammatory activity of terminal ileal Crohn disease in children and young adults and to assess whether simplified MaRIA scores change after biologic medical therapy. METHODS. This analysis was ancillary to a previously reported primary prospective research investigation. The study included 20 children and young adults with newly diagnosed ileal Crohn disease and 15 healthy control participants who underwent research small-bowel MRI examinations between December 2018 and October 2021. The participants with Crohn disease underwent baseline MRI and MRI 6 weeks and 6 months after beginning anti-tumor necrosis factor α-treatment as well as weighted pediatric Crohn disease activity index (wPCDAI) and C-reactive protein (CRP) assessment on the day of each examination. Control participants underwent one MRI examination. Four pediatric radiologists independently assigned simplified MaRIA scores using axial and coronal T2-weighted SSFSE images. Median simplified MaRIA score among readers was computed. Interreader agreement was assessed with Fleiss kappa coefficients and intra-class correlation coefficient (ICC). Analysis included the Mann-Whitney U test, Friedman test, and Spearman rank correlation. RESULTS. Simplified MaRIA scores (across time points and study groups) had substantial interreader agreement (κ = 0.65 [95% CI, 0.56-0.74]; ICC, 0.71 [95% CI, 0.63-0.78]). Median scores were higher in participants with Crohn disease at baseline than in healthy control participants (3.5 [IQR, 2.5-4.9] vs 0.5 [IQR, 0-2.0]; p < .001). Scores decreased after medical treatment in participants with Crohn disease (p = .005). The median score was 3.5 (IQR, 2.5-4.9) at baseline, 2.3 (IQR, 1.6-3.9) at 6 weeks, and 2.0 (IQR, 0.5-2.5) at 6 months. In participants with Crohn disease, median scores had significant correlations with wPCDAI (ρ = 0.46 [95% CI, 0.18-0.64]; p < .001) and CRP level (ρ = 0.48 [95% CI, 0.27-0.65]; p < .001). CONCLUSION. Radiologists had substantial agreement in use of simplified MaRIA scores to assess intestinal inflammation in ileal Crohn disease. Scores changed over time after medical therapy. CLINICAL IMPACT. The results support the simplified MaRIA score as an objective MRI-based clinical measure of intestinal inflammation in children and young adults with Crohn disease.

Evaluation of Fecal Calprotectin, Serum C-Reactive Protein, Erythrocyte Sedimentation Rate, Seromucoid and Procalcitonin in the Diagnostics and Monitoring of Crohn's Disease in Children.

Background: The development of diagnostic and monitoring algorithms for Crohn’s disease based on non-invasive methods is of particular importance in children and is the subject of many studies. Objectives: Evaluate the usefulness of fecal calprotectin, serum C-reactive protein, erythrocyte sedimentation rate, seromucoid and procalcitonin in the differential diagnosis of non-inflammatory gastrointestinal tract diseases and Crohn’s disease in children and their usefulness in determining the phenotype of Crohn’s disease. Material and methods: Forty-seven children with non-inflammatory gastrointestinal tract diseases and fifty-four with Crohn’s disease were enrolled. Clinical and endoscopic activity was evaluated based on the Pediatric Crohn’s Disease Activity Index (PCDAI) and the Simple Endoscopic Score for Crohn’s Disease (SES-CD). Results: Fecal calprotectin, C-reactive protein, erythrocyte sedimentation rate and seromucoid were significantly higher in children with Crohn’s disease than in controls (p < 0.001). Fecal calprotectin correlated with clinical and endoscopic activity according to the Pediatric Crohn’s Disease Activity Index (r = 0.338; p = 0.012) and the Simple Endoscopic Score for Crohn’s Disease (r = 0.428; p = 0.001). Non-invasive biomarkers did not correlate with the location and clinical manifestation of Crohn’s disease. Conclusions: Fecal calprotectin, C-reactive protein, erythrocyte sedimentation rate and seromucoid are useful in the differentiation of Crohn’s disease from non-inflammatory gastrointestinal tract diseases in children and in monitoring the clinical course of Crohn’s disease, but not in evaluating activity and phenotype of the disease.

Outcomes of Pediatric Patients with Crohn's Disease Received Infliximab or Exclusive Enteral Nutrition during Induction Remission.

Background Both exclusive enteral nutrition (EEN) and infliximab (IFX) are recommended as induction therapy for pediatric Crohn's disease (CD). Our aim was to compare long-term disease outcomes of patients initially received with either IFX or EEN. Methods Medical records of newly diagnosed, therapy naïve pediatric patients with CD received with IFX or EEN as induction therapy were retrospectively enrolled. Pediatric Crohn's disease activity index (PCDAI), Crohn's disease endoscopic index of severity (CDEIS), and other clinical data were compared pre- and postinduction therapy in two groups. The sustained remission rates and time coupled with body mass index (BMI) and height for age (HFA) changes were evaluated during more than 2-year long-term follow-up. Results We collected data from 58 children with CD used IFX (23) or EEN (35) as induction remission therapy from January 2015 through June 2021 in our single-center. The median follow-up after starting IFX or EEN was 12.2 months (6.5–18.0months) and 18.9 months (7.1–30.7months), respectively. The proportion clinical and endoscopic remission in EEN (88.57% and 68.75%) was similar with that of IFX (73.91% and 80.77%) after induction therapy. No significant differences were also observed in BMI and HFA recovery between two groups. Among those who achieved clinical or endoscopic remission or endoscopic response, the sustained remission rates and time did not reveal any significant differences for those 10 patients who used 6-mercaptopurine/methotrexate (6-MP/MTX) or 14 patients who used IFX as maintenance treatment during longitudinal follow-up. Conclusions Our study suggested that EEN treatment is similar with IFX therapy in short-term outcomes, and EEN+6-MP/MTX treatment is comparable with IFX+IFX therapy in long-term outcomes.

Methotrexate for Primary Maintenance Therapy in Mild-to-Moderate Crohn Disease in Children.

Despite limited data, methotrexate (MTX) is often used as primary maintenance therapy in pediatric Crohn disease (CD). We sought to assess the effectiveness of MTX as "initial" primary maintenance therapy in newly diagnosed mild/moderate pediatric CD and ascertain baseline predictive factors. Single-center 10-year retrospective review of newly diagnosed CD patients treated with MTX as primary maintenance therapy. We compared baseline characteristics of those patients with sustained response/clinical remission to those patients who escalated to anti-TNF therapy within 1 year. Pediatric Crohn Disease Activity Index (PCDAI) ≤ 10 defined remission. We identified 65 patients (mean age, 11.8 years; 72 % male; mean ± SD PCDAI, 17.8 ± 10.5) who started MTX ≤4 months of diagnosis as their primary maintenance therapy. Initial therapy prior to MTX was corticosteroids (CS) (54/65), defined diet (4/65), and combination CS/diet (6/65). Oral dosing was used in 55%; mean dose was 11.4 mg/m 2 orally and 12.5 mg/m 2 subcutaneously. At 1 year, 36 of 65 (55%) were on MTX monotherapy, and of those, 32 of 36 were in clinical remission; 81% were in steroid-free remission for the year following induction. For the 36 patients on MTX at 1 year, 14 (39%) had gross mucosal healing (22% of the original cohort). Ten additional patients had mucosal improvement (37% of total healed/improved). Fifteen patients (23%) were early failures, transitioning to anti-TNF ≤4 months. Baseline PCDAI, hemoglobin, ESR, albumin, and route of administration were not predictive of outcome. MTX was well tolerated in our cohort, with only 1 patient stopping due to elevated aminotransferases. No patient required CD surgery in the 1-year follow-up. MTX may have a primary maintenance role in mild/moderate CD.

Diagnostic Value of Quantitative Contrast-Enhanced Ultrasound in Comparison to Endoscopy in Children With Crohn's Disease.

Quantitative contrast-enhanced US (CEUS) provides objective evaluation of bowel wall perfusion and has been reported as a useful method for evaluating Crohn's disease (CD) activity in children. We tested its' diagnostic accuracy in comparison to endoscopy and evaluated its' usefulness in comparison to Pediatric Crohn's Disease Activity Index (PCDAI) and fecal Calprotectin (FC). Children with CD and thickened bowel wall on abdominal US were prospectively enrolled. Disease activity was evaluated with quantitative CEUS, PCDAI and FC and compared to a simple endoscopic score for Crohn's disease (SES-CD). Spearman's correlation and Cohen's kappa statistic between the SES-CD and other disease activity measures were performed and diagnostic accuracies calculated. 36 children 3.5-18 years old (mean age 14 years) were included. The quantitative CEUS had 78.57% sensitivity (95%CI 0.59-0.92), 100% specificity (95%CI 0.63-1.0) and 83.33% diagnostic accuracy (95% CI 0.67-0.94). The concordance remission agreement with endoscopy was substantial for quantitative CEUS and PCDAI (quantitative CEUS: κ=0.62; 95% CI 0.363-0.877; PCDAI: κ=0.615; 95% CI 0.311-0.920), but only fair for FC (κ=0.389; 95% CI 0.006-0.783). Correlation between all measures and endoscopy was moderate and statistically significant (quantitative CEUS: rs =0.535, PCDAI: rs =0.543, FC: rs =0.497). Quantitative CEUS has a potential of becoming a complementary method for evaluation of CD activity in children due to its' high specificity in comparison to endoscopy. Lower sensitivity makes it deficient as a single measure and further management should be guided by PCDAI and FC results as well.

Meta-analysis: efficacy of exclusive enteral nutrition as induction therapy on disease activity index, inflammation and growth factors in paediatric Crohn's disease.

There is evidence of inconsistency in sequelae of exclusive enteral nutrition (EEN) as induction therapy in paediatric patients with Crohn's disease (CD). To investigate the potential effects of EEN on paediatric Crohn's disease activity index (PCDAI), inflammation and biochemical parameters in paediatric patients with CD. We performed a comprehensive systematic search of PubMed/MEDLINE, Web of Science, SCOPUS and Embase until 8 January 2022 regardless of the time of publication or language. Random-effects model was applied to combine the datasets. The main outcomes were analysed through mean difference (MD) and its 95% confidence interval (CI). Forty six studies met eligibility criteria and were included in the meta-analysis. Pooled findings indicated that PCDAI score (MD of -27.24; 95% CI -31.84 to -22.64), calprotectin (MD of -842.83 mg/kg; CI -1018.24 to -667.42), CRP (pooled MD of -2.36 mg/dl; CI -2.68 to -2.03), and ESR (MD of -21.09 mm/h; CI -23.79 to -18.38), albumin (MD of 0.65 g/dl; CI 0.58 to 0.72), haemoglobin (MD of 1.12 g/dl; CI 0.87 to 1.37), weight (MD of 4.30 kg; CI 3.39 to 5.22), and height (MD of 0.98 cm; CI 0.35 to 1.62) improved significantly with EEN. Adherence to EEN can have significant, beneficial effects as induction therapy in paediatric patients with CD.

Effectiveness of induction therapy with exclusive enteral nutrition in pediatric Crohn's disease

To evaluate the effectiveness of induction therapy with exclusive enteral nutrition (EEN) in pediatric Crohn's disease (CD). A retrospective analysis was performed on the medical data of 62 children with CD who received EEN in Children's Hospital, Zhejiang University School of Medicine, from March 2013 to August 2021. The medical data included general information and height, weight, Pediatric Crohn's Disease Activity Index (PCDAI), Crohn's Disease Endoscopic Index of Severity, C-reactive protein, erythrocyte sedimentation rate, and serum albumin level before treatment and after 8 weeks of treatment. The changes in the above indicators were compared before and after treatment. Among the 62 children with CD, there were 39 boys (63%) and 23 girls (37%), with a mean age of (11.9±3.0) years at diagnosis. Among the 55 children who completed EEN treatment for at least 8 weeks, 48 (87%) achieved clinical remission at week 8. PCDAI at week 8 was significantly lower than that before treatment (P<0.001). Except for 17 children with involvement of the small intestine alone and 3 children with involvement of the colon who did not receive colonoscopy reexamination, the remaining 35 children with involvement of the colon received colonoscopy reexamination after the 8-week EEN treatment. Of the 35 children, 29 (83%) achieved mucosal healing. As for the 48 children who achieved clinical remission at week 8, there were significant improvements in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P<0.01). As for the 7 children who did not achieve clinical remission at week 8, there were no significant changes in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P>0.05). The 8-week EEN treatment has a good effect on clinical remission and mucosal healing in children with CD. For the children with CD achieving clinical remission, EEN can improve their height and body mass index.