Outcome in pediatric celiac disease is independent of the diagnostic approach in patients with high antibody levels.

OBJECTIVES: European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines enable the diagnosis of celiac disease (CD) without biopsies in patients with immunoglobulin A (IgA)-antibodies against tissue transglutaminase (TGA-IgA) ≥ 10× the upper limit of normal (ULN) and positivity of endomysial antibodies in a second blood sample. Limited data exist comparing the biopsy versus the nonbiopsy diagnostic approach regarding long-term outcomes in CD patients. Our study aimed to investigate the influence of the diagnostic approach on adherence to gluten-free diet (GFD), serological remission (defined as normalization of TGA-IgA during follow-up (FU)) and clinical remission in CD patients with TGA-IgA ≥ 10× ULN. METHODS: Retrospective multicenter study. Patients with CD and TGA-IgA ≥ 10× ULN at diagnosis were included in the study. Patients with confirmed diagnosis by biopsy were compared to patients diagnosed by nonbiopsy approach using univariate analysis, Kaplan-Meier survival curve, and logistic regression models. RESULTS: A total of 282 CD patients (192 [68.1%] in the biopsy group; 90 [31.9%] in the nonbiopsy group) were analyzed. The median time to normalization of TGA-IgA was 16.5 months [interquartile range, IQR: 13, 28] in the biopsy and 15 months [IQR: 12, 26] in the nonbiopsy group; p = 0.14). Rates of normalized TGA-IgA at first to third-year FU were comparable between both groups. Adherence to GFD did not seem to be influenced by the diagnostic approach. CONCLUSIONS: The nonbiopsy approach is not inferior to the biopsy approach in terms of adherence to GFD and serological remission in patients with CD.

Bedside Intestinal Ultrasound Predicts Disease Severity and the Disease Distribution of Pediatric Patients With Inflammatory Bowel Disease: A Pilot Cross-sectional Study.

BACKGROUND: Intestinal ultrasound (IUS) is a noninvasive tool to assess bowel inflammation. There is a paucity of data on its accuracy in pediatric patients. AIM: The aim of this study is to evaluate the diagnostic performance of bowel wall thickness (BWT) measured using IUS compared with endoscopic disease activity in children suspected of having inflammatory bowel disease (IBD). METHODS: We conducted a single-center cross-sectional pilot study of pediatric patients suspected to have previously undiagnosed IBD. Endoscopic inflammation was graded using segmental scores of the Simple Endoscopic Score for Crohn's Disease (SES-CD) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and classified as having healthy, mild, or moderate/severe disease activity. Association between BWT and endoscopic severity was assessed using the Kruskal-Wallis test. The diagnostic performance of BWT to detect active disease at endoscopy was evaluated using the area under the receiver operating characteristic curve; sensitivity and specificity were calculated. RESULTS: In all, 174 bowel segments in 33 children were assessed by IUS and ileocolonoscopy. An elevated median BWT was associated with increased bowel segment disease severity, classified by the SES-CD (P < .001) and the UCEIS (P < .01). Using a cutoff value of 1.9 mm, we found that the BWT had an area under the receiver operating characteristic curve of 0.743 (95% CI, 0.67-0.82), a sensitivity of 64% (95% CI, 53%-73%), and a specificity of 76% (95% CI, 65%-85%) to detect inflamed bowel. CONCLUSION: Increasing BWT is associated with increasing endoscopic activity in pediatric IBD. Our study suggests that the optimal BWT cutoff value for detecting active disease may be less than that seen in adults. Additional pediatric studies are needed.

Increasing bowel wall thickness (BWT) is associated with increasing IBD endoscopic scores on colonoscopy. There is moderate to fair agreement between the prediction of IBD diagnosis and Paris classification using intestinal ultrasound (IUS). Bowel wall thickness cutoff values to detect inflamed bowel segments are likely lower for children with IBD than for adults, although further studies with wider age ranges are needed to confirm this finding.

The negative association of the SARS-CoV-2 pandemic with the health of mother and child considering maternal childhood maltreatment.

BACKGROUND: Social distancing strategies during the SARS-CoV-2 pandemic have left families facing a variety of different constraints. Especially in this stressful time, children need a stable parental home to prevent developmental consequences. Additional risk factors such as maternal childhood maltreatment (CM) may affect mother's psychosomatic health and children's physical well-being in this period. OBJECTIVE: It was aimed to analyze the associations between maternal CM, mother's mental health, and children's physical complaints during the SARS-CoV-2-pandemic. METHOD: Mothers of a well-documented birth cohort from a longitudinal study were included in this study. Psychosomatic health was assessed with the PHQ-D and children's physical health with the GBB-KJ during the pandemic. N = 159 mothers completed the online survey. To describe the maternal CM, data from a longitudinal survey were used. RESULTS: The calculation of three mediation analyses demonstrate that maternal depression symptoms (c-path: ß = 0.10, p = .02; c'-path: ß = 0.07, p = .13), somatic symptoms (c-path: ß = 0.10, p = .02; c'-path: ß = 0.07, p = .13) and psychosomatic symptoms (c-path: ß = 0.10, p = .02; c'-path: ß = 0.06, p = .19) fully mediate the relationship between CM and children's physical health complaints. CONCLUSIONS: Maternal CM experiences seem to be one relevant risk factor during the pandemic and seem to influence the way in which parents deal with stressful situations and increase the risk for depressive symptoms. The present results highlight the importance to provide individually adjusted assistance to help the families to get through the pandemic.

Characterization of the Transition Zone in Short Segment Hirschsprung Disease Using Calretinin Immunostaining.

Introduction: The detailed expression pattern of calretinin immunohistochemistry in the transition zone (TZ) of Hirschsprung disease (HSCR) has not yet been reported. This study aims to examine the value of calretinin immunohistochemistry for more accurately determining the distal and proximal border of the TZ in short segment HSCR. Methods: Specimens of pull-through surgery from 51 patients with short form of HSCR were analyzed on two longitudinal strips using hematoxylin and eosin (H&E) staining and calretinin immunohistochemistry. Results: In all but two patients, the first appearance of calretinin expression was seen on mucosal nerve fibers before the appearance of any ganglion cells, indicating the distal border of the TZ. The maximum distance between the distal border of the TZ and the proximal border of the TZ, defined by ganglion cells in a normal density on H&E stained sections, a strong calretinin expression on mucosal nerve fibers and in >80% of submucosal and myenteric ganglion cells, with no nerve hypertrophy and absence of ganglionitis was 60 mm. Conclusion: The distal border of the TZ is characterized by calretinin positive intramucosal neurites in nearly all of short form of HSCR and not by calretinin expression on ganglion cells.

Nutritional Aspects of Pediatric Gastrointestinal Diseases.

In the last decade, the role of nutritional management in pediatric gastrointestinal diseases has gained increasing popularity. Disease-specific diets have been introduced as conventional treatments by international guidelines. Patients tend to more willingly accept food-based therapies than drugs because of their relatively "harmless" nature. Apart from a diet's therapeutic role, nutritional support is crucial in maintaining growth and improving clinical outcomes in pediatric patients. Despite the absence of classical "side effects", however, it should be emphasized that any dietary modification might have negative consequences on children's growth and development. Hence, expert supervision is always advised, in order to support adequate nutritional requirements. Unfortunately, the media provide an inaccurate perception of the role of diet for gastrointestinal diseases, leading to misconceptions by patients or their caregivers that tends to overestimate the beneficial role of diets and underestimate the potential adverse effects. Moreover, not only patients, but also healthcare professionals, have a number of misconceptions about the nutritional benefits of diet modification on gastrointestinal diseases. The aim of this review is to highlight the role of diet in pediatric gastrointestinal diseases, to detect misconceptions and to give a practical guide for physicians on the basis of current scientific evidence.

Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease.

Rates of pediatric Crohn's disease (CD) and ulcerative colitis (UC) are increasing globally. Differentiation of these inflammatory bowel disease (IBD) subtypes however can be challenging when relying on invasive endoscopic approaches. We sought to identify urinary metabolic signatures of pediatric IBD at diagnosis, and during induction treatment. Nontargeted metabolite profiling of urine samples from CD (n = 18) and UC (n = 8) in a pediatric retrospective cohort study was performed using multisegment injection-capillary electrophoresis-mass spectrometry. Over 122 urinary metabolites were reliably measured from pediatric IBD patients, and unknown metabolites were identified by tandem mass spectrometry. Dynamic changes in sum-normalized urinary metabolites were also monitored following exclusive enteral nutrition (EEN) or corticosteroid therapy (CS) in repeat urine samples collected over 8 weeks. Higher urinary excretion of indoxyl sulfate, hydroxyindoxyl sulfate, phenylacetylglutamine, and sialic acid were measured in CD as compared to UC patients, but lower threonine, serine, kynurenine, and hypoxanthine (p < 0.05). Excellent discrimination of CD from UC was achieved based on the urinary serine:indoxylsulfate ratio (AUC = 0.972; p = 3.21 × 10-5). Urinary octanoyl glucuronide, pantothenic acid, and pyridoxic acid were also identified as specific dietary biomarkers of EEN in pediatric IBD patients who achieved clinical remission. This work may complement or replace existing strategies in the diagnosis and early management of children with IBD.

The Association between LGBTQIA+ Self-Identification and Factors Facilitating Homelessness: A Scoping Review of the Occupational Therapy Peer-Reviewed Literature.

The purpose of this paper was to perform a scoping review examining the occupational therapy peer-reviewed literature regarding the LGBTQIA+ community to (a) determine what types of scholarship have been generated and (b) whether the association between LGBTQIA+ self-identification and homelessness has been identified and addressed in occupational therapy practice. A database search of seven peer-reviewed, health care publication indexes, with 19 key search terms was performed. The database search targeted articles published prior to January 2020. Fifty-three articles were identified within the occupational therapy literature and addressing the LGBTQIA+ community. The majority of this literature (n = 40) was exploratory studies through which researchers sought to better understand the unique needs of subgroups within the LGBTQIA+ community. Only three articles addressed the link between LGBTQIA+ self-identification and homelessness with no articles that addressed evaluation and intervention of the factors predisposing this population to homelessness. As occupational therapists have a unique skill set that could be used to help LGBTQIA+ community members transition from and remain free from homelessness, occupational therapy researchers must develop and assess interventions that target these factors. Occupational therapy educators should develop and assess curricular programming to heighten student comfort and preparedness in service delivery to this community.

Nutritional Therapies and Their Influence on the Intestinal Microbiome in Pediatric Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic, autoimmune disorder of the gastrointestinal tract with numerous genetic and environmental risk factors. Patients with Crohn's disease (CD) or ulcerative colitis (UC) often demonstrate marked disruptions of their gut microbiome. The intestinal microbiota is strongly influenced by diet. The association between the increasing incidence of IBD worldwide and increased consumption of a westernized diet suggests host nutrition may influence the progression or treatment of IBD via the microbiome. Several nutritional therapies have been studied for the treatment of CD and UC. While their mechanisms of action are only partially understood, existing studies do suggest that diet-driven changes in microbial composition and function underlie the diverse mechanisms of nutritional therapy. Despite existing therapies for IBD focusing heavily on immune suppression, nutrition is an important treatment option due to its superior safety profile, potentially low cost, and benefits for growth and development. These benefits are increasingly important to patients. In this review, we will describe the clinical efficacy of the different nutritional therapies that have been described for the treatment of CD and UC. We will also describe the effects of each nutritional therapy on the gut microbiome and summarize the strength of the literature with recommendations for the practicing clinician.

Lyophilized fecal short-chain fatty acid and electrolyte determination by capillary electrophoresis with indirect UV detection for assessment of pediatric inflammatory bowel disease.

Short-chain fatty acids (SCFAs) and electrolytes are major constituents of human feces involved in maintaining gastrointestinal homeostasis that underlie complex diet, host and microbiome interactions. Reliable quantification of SCFAs and electrolytes is challenging given the heterogeneity of stool specimens from pediatric patients with diarrhea-predominate inflammatory bowel disease (IBD). Herein, we introduce two validated methods for determination of 3 SCFAs and 5 electrolytes consistently quantified from fecal extracts when using capillary electrophoresis with indirect UV detection (CE-iUV), where concentrations are normalized to total dried weight (mmol/kg d.w.). Lyophilization facilitates sample handling and extraction of heterogeneous stool specimens (∼ 15 mg) from a cohort of children with Crohn's disease (CD, n = 12) and ulcerative colitis (UC, n = 10) treated with exclusive enteral nutrition (EEN) or corticosteroid (CS) therapy to induce remission, respectively. Good technical precision (mean CV = 13 %, n = 14) and accuracy (recovery from 84 to 116%) is demonstrated for SCFAs and electrolytes from freeze dried stool extracts using a modified Bligh-Dyer protocol with low micromolar detection limits (∼ 2-15 µM). Fecal butyrate is 2.6-fold higher in CD as compared to UC patients (effect size = 1.51; p = 0.00291), and there is a strong co-linearity between fecal butyrate and acetate (r = 0.835) unlike propionate, which is correlated with fecal calprotectin (r = 0.517), a protein biomarker of intestinal inflammation. Also, a longitudinal study of matching stool samples collected from a sub-set of IBD patients revealed about a 7-fold enrichment in magnesium and calcium following 4 weeks of EEN as compared to baseline (F > 4.1 ; p < 0.05) unlike the CS treatment arm with no changes in other fecal SCFAs and electrolytes, including sodium, potassium, and ammonium. CE-iUV enables rapid fecal SCFA and electrolyte determination as required for new insights into the role of gut dysbiosis in IBD, as well as treatment monitoring of nutritional interventions that stabilize the disease course in affected children.

Anemia in Children With Inflammatory Bowel Disease: A Position Paper by the IBD Committee of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition.

Anemia is one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD). It can be asymptomatic or associated with nonspecific symptoms, such as irritability, headaches, fatigue, dizziness, and anorexia. In IBD patients, the etiology of anemia is often multifactorial. Various causes include iron deficiency, anemia of inflammation and chronic disease, vitamin deficiencies, hemolysis, or myelosuppressive effect of drugs. Anemia and iron deficiency in these patients may be underestimated because of their insidious onset, lack of standardized screening practices, and possibly underappreciation that treatment of anemia is also required when treating IBD. Practitioners may hesitate to use oral preparations because of their intolerance whereas intravenous preparations are underutilized because of fear of adverse events, availability, and cost. Several publications in recent years have documented the safety and comparative efficacy of various intravenous preparations. This article reviews management of anemia in children with IBD, including diagnosis, etiopathogenesis, evaluation of a patient, protocol to screen and monitor patients for early detection and response to therapy, treatment including parenteral iron therapy, and newer approaches in management of anemia of chronic disease. This report has been compiled by a group of pediatric gastroenterologists serving on the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) IBD committee, in collaboration with a pediatric hematologist, pharmacist, and a registered dietician who specializes in pediatric IBD (IBD Anemia Working Group), after an extensive review of the current literature. The purpose of this review is to raise awareness of under-diagnosis of anemia in children with IBD and make recommendations for screening, testing, and treatment in this population.

Do You See What I See? An Assessment of Endoscopic Lesions Recognition and Description by Gastroenterology Trainees and Staff Physicians.

BACKGROUND: Gastroenterologists should accurately describe endoscopic findings and integrate them into management plans. We aimed to determine if trainees and staff are describing inflammatory bowel disease (IBD) lesions in a similar manner. METHODS: Using 20 ileocolonoscopy images, participants described IBD inflammatory burden based on physician severity rating, and Mayo endoscopic score (MES) (ulcerative colitis [UC]) or simple endoscopic score (SES-CD) (Crohn's disease [CD]). Images were selected based on agreement by three IBD experts. Findings of varying severity were presented; 10 images included a question about management. We examined inter-observer agreement among trainees and staff, compared trainees to staff, and determined accuracy of response comparing both groups to IBD experts. RESULTS: One hundred and twenty-nine staff and 47 trainees participated from across Canada. There was moderate inter-rater agreement using physician severity rating (κ = 0.53 UC and 0.52 CD for staff, κ = 0.51 UC and 0.43 CD for trainees). There was moderate inter-rater agreement for MES for staff and trainees (κ = 0.49 and 0.48, respectively), but fair agreement for SES-CD (κ = 0.37 and 0.32, respectively). For accuracy of response, the mean score was 68.7% for staff and 63.7% for trainees (P = 0.028). Both groups identified healed bowel or severe disease better than mild/moderate (P < 0.05). There was high accuracy for management, but staff scored higher than trainees for UC (P < 0.01). CONCLUSION: Inter-rater agreement on description of IBD lesions was moderate at best. Staff and trainees more accurately describe healed and severe disease, and better describe lesions in UC than CD.

Effect of Exclusive Enteral Nutrition and Corticosteroid Induction Therapy on the Gut Microbiota of Pediatric Patients with Inflammatory Bowel Disease.

INTRODUCTION: Exclusive enteral nutrition (EEN) and corticosteroids (CS) are effective induction therapies for pediatric Crohn's Disease (CD). CS are also therapy for ulcerative colitis (UC). Host-microbe interactions may be able to explain the effectiveness of these treatments. This is the first prospective study to longitudinally characterize compositional changes in the bacterial community structure of pediatric UC and CD patients receiving EEN or CS induction therapy. METHODS: Patients with diagnoses of CD or UC were recruited from McMaster Children's Hospital (Hamilton, Canada). Fecal samples were collected from participants aged 5-18 years old undergoing 8 weeks of induction therapy with EEN or CS. Fecal samples were submitted for 16S rRNA sequencing. The Shannon diversity index and the relative abundance of specific bacterial taxa were compared using a linear mixed model. RESULTS: The clustering of microbiota was the highest between patients who achieved remission compared to patients still showing active disease (p = 0.029); this effect was independent of the diagnosis or treatment type. All patients showed a significant increase in Shannon diversity over the 8 weeks of treatment. By week 2, a significant difference was seen in Shannon diversity between patients who would go on to achieve remission and those who would not. CONCLUSION: The gut microbiota of pediatric UC and CD patients was most influenced by patients' success or failure to achieve remission and was largely independent of the choice of treatment or disease type. Significant differences in Shannon diversity indices occurred as early as week 2 between patients who went on to achieve remission and those who continued to have active disease.

Faecal Calprotectin Predicts Endoscopic and Histological Activity in Clinically Quiescent Ulcerative Colitis.

INTRODUCTION: Faecal calprotectin [FC] is a reliable surrogate marker for disease activity in ulcerative colitis [UC]; however, there are no consensus cut-off values for remission. The study aim was to correlate FC with Mayo Endoscopic Score [MES] and histological disease activity of UC patients in clinical remission. METHODS: Our study recruited adult UC patients at the McGill IBD Center between 2013 and 2017. Patients in clinical remission [partial Mayo score ≤2], undergoing endoscopy for disease activity or dysplasia surveillance, were enrolled. Before bowel preparation, FC was collected. MES was documented during colonoscopy. Biopsies were taken; histological activity was assessed using Geboes score and the presence of basal plasmacytosis. RESULTS: A total of 185 patients were recruited. The area under the curve [AUC] in receiver operating characteristic [ROC] analysis to predict MES 1-3 [from 0] was 0.743 [95% CI 0.67-0.82; p <0.001] with an FC cut-off value 170 µg/g [64% sensitivity, 74% specificity], and to predict MES 2-3 [from 0-1] was 0.722 [95% CI 0.61-0.83; p <0.001] with an FC cut-off value 170 µg/g [69% sensitivity, 65% specificity]. To differentiate MES 0 from MES 1, an FC value 130 µg/g yields a 70% sensitivity and 68% specificity. The AUC in ROC analysis to predict Geboes <3.1 was 0.627 [95% CI 0.55-0.71; p = 0.003], with an FC value 135 µg/g [54% sensitivity, 69% specificity]. CONCLUSIONS: In this large study, FC ≥170 µg/g predicts endoscopic activity and FC ≥135 µg/g predicts histological activity. Therefore in clinical practice, lower faecal calprotectin thresholds can be chosen to optimise identification of patients with ongoing endoscopic and histological disease activity.

Endoscopic scoring systems for the evaluation and monitoring of disease activity in Crohn's disease.

Crohn's disease is a chronic relapsing idiopathic condition that can affect any part of the gastrointestinal tract. It has been shown that mucosal healing is associated with improved clinical outcomes such as reduced risk of surgery, hospitalization and complications. Nowadays mucosal healing is considered the optimal target of medical therapy. To evaluate the mucosa in an objective and standardized manner, it is important to rely on accurate and validated endoscopic scores. The Crohn's disease endoscopic index of severity, the simple endoscopic score for Crohn's disease as well as the Rutgeerts score will be reviewed. Their clinical implications and limitations will be discussed.

Web-Based Tools for Educating Caregivers About Childhood Fever: A Randomized Controlled Trial.

OBJECTIVES: Fever is a common reason for an emergency department visit and misconceptions abound. We assessed the effectiveness of an interactive Web-based module (WBM), read-only Web site (ROW), and written and verbal information (standard of care [SOC]) to educate caregivers about fever in their children. METHODS: Caregivers in the emergency department were randomized to a WBM, ROW, or SOC. Primary outcome was the gain score on a novel questionnaire testing knowledge surrounding measurement and management of fever. Secondary outcome was caregiver satisfaction with the interventions. RESULTS: There were 77, 79, and 77 participants in the WBM, ROW, and SOC groups, respectively. With a maximum of 33 points, Web-based interventions were associated with a significant mean (SD) pretest to immediate posttest gain score of 3.5 (4.2) for WBM (P < 0.001) and 3.5 (4.1) for ROW (P < 0.001) in contrast to a nonsignificant gain score of 0.1 (2.7) for SOC. Mean (SD) caregiver satisfaction scores (out of 32) for the WBM, ROW, and SOC groups were 22.6 (3.2), 20.7 (4.3), and 17 (6.2), respectively. All groups were significantly different from one another in the following rank: WBM > ROW > SOC (P < 0.001). CONCLUSIONS: Web-based interventions are associated with significant improvements in caregiver knowledge about fever and high caregiver satisfaction. These interventions should be used to educate caregivers pending the demonstration of improved patient-centered outcomes.

Management of Paediatric Patients With Medically Refractory Crohn's Disease Using Ustekinumab: A Multi-Centred Cohort Study.

BACKGROUND: Ustekinumab [UST] is effective in the treatment of adults with moderate to severe Crohn's disease [CD]. There is a paucity of data on its use in children. AIM: To evaluate the response to UST in children with moderate to severe CD. METHODS: This multicentre retrospective cohort study identified children under 18 years old with CD, who received open-labelled subcutaneous UST. The primary outcome was changes in mean abbreviated Paediatric Crohn's Disease Activity Index [aPCDAI] between baseline and 3 and 12 months, and rate of clinical remission at 3 and 12 months. Secondary outcomes were clinical response at the same time points, changes in C-reactive protein [CRP] and albumin, improvement in growth parameters, and rate of adverse events. RESULTS: A total of 44 patients who failed at least one biological treatment were identified. Linear mixed model [LMM] analysis revealed a statistically significant effect of UST (χ2[1] = 42.7, p = 1.2 × 10-8) which lowered the aPCDAI scores by about 16 ± 2.7 at 3 months, and 19.6 ± 2.9 at 12 months. At 12 months, 38.6% of the patients achieved clinical remission and 47.8% achieved clinical response. There was a significant increase in mean weight z-score of 0.48 [±0.13] [p <0.001] and in mean body mass index [BMI] z score of 0.66 [±0.16] [p <0.001]. The probability of remaining on UST at 12 months was 76.9%. The rate of adverse events was 12.4 per 1000 patient-months. CONCLUSIONS: Subcutaneous UST should be considered a viable therapeutic option for paediatric patients who are refractory to other biological agents. Prospective randomised trials are needed.