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Cross-sectional imaging is important in the assessment of transmural inflammation in Crohn's disease (CD). Small bowel involvement is often more extensive in pediatric CD, requiring a panentering measuring tool. We undertook to develop a magnetic resonance enterography (MRE)-based index that would measure inflammation in all segments of the intestine, without rectal contrast. Children with CD underwent ileocolonoscopy and MRE and half were prospectively followed for 18 months when MRE was repeated. Item generation and reduction were performed by a Delphi panel of pediatric radiologists, a systematic literature review, a cross-sectional study of 48 MREs, and a steering committee. Formatting and weighting were performed using multivariate modeling adjusted by a steering committee. MREs were read locally and centrally. Reliability, validity, and responsiveness were determined using several clinimetric and psychometric approaches. Thirty items were initially generated and reduced to 5 using regression analysis on 159 MREs: wall thickness, wall diffusion weighted imaging, ulcerations, mesenteric edema, and comb sign. In the validation cohort of 81 MREs, the weighted global PICMI correlated well with the radiologist global assessment (r = 0.85; P <.001) and with the simple endoscopic score in a subsample with ileocolonic disease (r = 0.63; P <.001). Interobserver and test-retest reliability were high (interclass correlation coefficients, 0.84; 95% confidence interval [CI], 0.79–0.87; and 0.81, 95% CI, 0.65–0.90, respectively; both P <.001). Excellent responsiveness was found at repeated visits (n = 116 MREs; area under the receiver operating characteristic curve 0.96; 95% CI, 0.93–0.99). Transmural healing was defined as PICMI ≤10 and response as a change of >20 points with excellent discriminative validity (area under the receiver operating characteristic curve = 0.96; 95% CI, 0.93–0.99). The PICMI is a valid, reliable, and responsive index for assessing transmural inflammation in pediatric CD. It scores the entire bowel length and does not require intravenous contrast or rectal enema and, therefore, is suitable for use in children. (ClinicalTrials.gov , Number: NCT01881490.) [Display omitted] We have developed a validated score, called the Pediatric Inflammatory Crohn's Magnetic Resonance Enterography Index, which quantifies the degree of inflammation in the bowel of children with Crohn's disease, as measured using magnetic resonance imaging of the bowel. [ABSTRACT FROM AUTHOR]

Background Free intestinal perforation in children with Crohn's disease (CD) is a rare, but serious complication that requires urgent surgical management. The incidence, contributing risk factors, diagnostic workup, and management strategies for these complex pediatric patients are not well established. Methods We present a recent case of free intestinal perforation in a patient with CD. In addition, a systematic review of the literature was conducted by searching the PubMed, Embase, Ovid, Scopus and Cochrane databases. Two authors independently extracted data, reviewed the abstracts, and assessed them for inclusion in the review. Results The literature review identified 21 pediatric patients documented in 14 publications; including our case, there are a total of 22 pediatric patients reported. The majority of patients presented with features of peritonitis. Perforation occurred early in the disease course (median 6.5 months), and was most commonly a single perforation in the ileum with active Crohn's disease (82%). Colonic perforation occurred in 18% of patients. All patients underwent urgent surgical management. Surgical approaches included resection of the diseased bowel segment with proximal diversion in eleven patients (50%), resection with primary anastomosis in 9 (41%) or direct suture repair in two (9%). Both patients who underwent simple primary repair developed post-operative complications. Conclusions Free intestinal perforation may occur at any age and stage of Crohn's disease. Three-dimensional imaging may be required to confirm the diagnosis. The management of free intestinal perforation in CD is surgical. This should involve resection of the involved segment with proximal diversion or resection with primary anastomosis in selected cases. Primary suture closure of the perforation is discouraged. [ABSTRACT FROM AUTHOR]

Burill Crohn’s convincing description of the disease that now carries his name conceived of the illness as arising exclusively from the terminal ileum, involving other sites only secondarily. As a result, he took the condition to be curable by an adequate operative resection. The current concept is that Crohn’s disease may affect any segment of the gastrointestinal tract. The practical implication of this change in thinking is the need to conserve bowel when weighing medical and surgical options for each child. Operations should be used to treat complications of the disease. Absolute indications for the surgery are uncommon and include perforation, bleeding, and refractory obstruction. The margins of resection need only include a short amount of grossly normal intestine. Strictureplasty to relieve obstruction without resection should be done when applicable. Maintenance medication after an operation to limit recurrence or recrudescence is frequently advocated. [Copyright &y& Elsevier]

Background: Crohn's disease is a chronic and unpredictable inflammatory bowel disease that leads to important psychosocial difficulties especially during sensitive developmental stages such as childhood and adolescence. While risk factors for mood disorders have been identified in the literature, those for quality of life and psychosocial functioning have not.Objective: This systematic review explored the determinants of quality of life and psychosocial adjustment to pediatric Crohn's disease.Method: Four international databases were consulted in March 2020: PubMed, PsychInfo, PubPsych and Cochrane Library. A series of keywords were entered in each database to identify the most recent relevant studies.Results: One hundred and sixty-eight articles were identified, of which twenty-nine met the inclusion criteria. The majority explored the determinants of quality of life, depression and anxiety, with a few focusing on psychosocial functioning. Consistently with the literature on psychological morbidity, disease activity and parental stress were also strong predictors of quality of life and psychosocial functioning. New evidence showed that abdominal pain, negative illness perceptions and internalizing symptoms were also common predictors of these outcomes.Conclusions: Some risk factors of quality of life, distress and psychosocial functioning are similar, which could indicate that some patients could be at risk of presenting an accumulation of difficulties adjusting to the disease. The identification of these risk factors is fundamental to propose appropriate interventions. Therapeutic education, therapies focused on pain management or on the parent-child relationship can be considered to allow a better adjustment or prevent difficulties. [ABSTRACT FROM AUTHOR]

Human gut development requires the orchestrated interaction of differentiating cell types. Here, we generate an in-depth single-cell map of the developing human intestine at 6–10 weeks post-conception. Our analysis reveals the transcriptional profile of cycling epithelial precursor cells; distinct from LGR5-expressing cells. We propose that these cells may contribute to differentiated cell subsets via the generation of LGR5-expressing stem cells and receive signals from surrounding mesenchymal cells. Furthermore, we draw parallels between the transcriptomes of ex vivo tissues and in vitro fetal organoids, revealing the maturation of organoid cultures in a dish. Lastly, we compare scRNA-seq profiles from pediatric Crohn's disease epithelium alongside matched healthy controls to reveal disease-associated changes in the epithelial composition. Contrasting these with the fetal profiles reveals the re-activation of fetal transcription factors in Crohn's disease. Our study provides a resource available at www.gutcellatlas.org , and underscores the importance of unraveling fetal development in understanding disease. • Single-cell RNA-seq map of the developing and pediatric human intestine • Cycling BEX5+ epithelial precursors are distinct from adult LGR5+ stem cells • Human fetal intestinal organoids mature in culture • Fetal transcription factors are reactivated in the Crohn's disease epithelium Elmentaite and Ross et al. generated a detailed single-cell RNA-seq map of the developing human intestine. Data analyses revealed the presence of an early intestinal epithelial precursor cell and the re-activation of fetal transcription factors in the intestinal epithelium of children diagnosed with Crohn's disease. The study provides a unique resource accessible to all researchers at www.gutcellatlas.org. [ABSTRACT FROM AUTHOR]

• Higher levels of perceived stress were associated with worse disease activity. • Lower relative abundances of bacteria in phylum Firmicutes in higher stress group. • Genus Anaerostipes was lower and Parabacteroides was higher in the high stress group. • Differences were independent of medications, disease severity, disease duration, diet. • Levels of the metabolite alanine were higher in youth with higher stress. Stress is associated with increased Crohn's Disease (CD) activity. This pilot study tested whether pediatric patients with CD reporting higher levels of perceived stress exhibited differences in the fecal microbiome and metabolome. The perceived stress scale (PSS) questionnaire was administered within 2 days of collecting a stool sample for microbiome (using 16S rRNA gene sequencing) and metabolome (using NMR metabolomics) analyses. Higher levels of perceived stress were correlated with increased disease activity on the short Pediatric Crohn's Disease Activity Index (sPCDAI). Patients with High PSS scores vs. Low PSS scores based on a median split had significantly lower relative abundances of Firmicutes and Anaerostipes , as well as higher relative abundances of Parabacteroides. Fecal alanine and nicotinate were also significantly different in patients with High vs. Low PSS Scores. This pilot study suggests that the fecal microbiome and metabolome differs in pediatric patients with CD and high perceived stress. [ABSTRACT FROM AUTHOR]

Background & Aims: We examined the incidence of Crohn''s disease (CD)-related surgery in a multi-center, inception cohort of pediatric patients with CD. We also examined the effect of starting immunomodulator therapy within 30 days of diagnosis. Methods: Data from 854 children with CD from the Pediatric Inflammatory Bowel Disease Collaborative Research Group who were diagnosed with CD between 2002 and 2008 were analyzed. Results: Overall, 76 (9%) underwent a first CD-related surgery, 57 (7%) underwent a first bowel surgery (bowel resection, ostomy, strictureplasty, or appendectomy), and 19 (2%) underwent a first non-bowel surgery (abscess drainage or fistulotomy). The cumulative risks for bowel surgery, non-bowel surgery, and all CD-related surgeries were 3.4%, 1.4%, and 4.8%, respectively, at 1 year after diagnosis and 13.8%, 4.5%, and 17.7%, respectively, at 5 years after diagnosis. Older age at diagnosis, greater disease severity, and stricturing or penetrating disease increased the risk of bowel surgery. Disease between the transverse colon and rectum decreased the risk. Initiation of immunomodulator therapy within 30 days of diagnosis, sex, race, and family history of inflammatory bowel disease did not influence the risk of bowel surgery. Conclusions: In an analysis of pediatric patients with CD, the 5-year cumulative risk of bowel surgery was lower than that reported in recent studies of adult and pediatric patients but similar to that of a recent retrospective pediatric study. Initiation of immunomodulator therapy at diagnosis did not alter the risk of surgery within 5 years of diagnosis. [Copyright &y& Elsevier]