ADALIMUMAB VERSUS INFLIXIMAB IN LUMINAL PEDIATRIC CROHN'S DISEASE: COMPARABLE OUTCOMES IN A PROSPECTIVE MULTICENTER COHORT STUDY.

BACKGROUND: This study compared real-world effectiveness between adalimumab (ADA) and infliximab (IFX) in children with Crohn's disease (CD). METHODS: Children enrolled into the prospective Canadian Children Inflammatory Bowel Disease Network (CIDsCaNN) National Inception Cohort between 2014 and 2020 who commenced ADA or IFX as first anti-tumor necrosis factor (antiTNF) agent for luminal CD were included. Multivariate logistic regression modelled the propensity of commencing ADA; propensity score matching was used to match IFX-treated children to ADA-treated children. The primary outcome at one year was steroid-free clinical remission (SFCR). Secondary outcomes at one year were I) combined SFCR and c-reactive protein (CRP) remission; II) treatment intensification; and III) antiTNF durability. Odds ratios (aOR) and hazard ratio (aHR) adjusted for concomitant immunomodulator use with 95% confidence interval (CI) are reported. RESULTS: In the propensity score matched cohort of 147 ADA-treated and 147 IFX-treated children, 92 (63%) ADA- and 87 (59%) IFX-treated children achieved SFCR at one year (aOR: 1.4, 95% CI 0.9-2.4); 75 of 140 (54%) ADA- and 85 of 144 (59%) IFX-treated children achieved combined SFCR and CRP remission (aOR: 1.0, 95% CI 0.6-1.6). ADA-treated children less frequently underwent treatment intensification (21 [14%]) compared to IFX-treated children (69 [47%]) (P<0.0001). Discontinuation of antiTNF occurred in 18 (12%) ADA-treated and 15 (10%) IFX-treated children (aHR: 1.2, 95% CI 0.6-2.2). CONCLUSION: Children with Crohn's disease achieved favourable outcomes at one year with either ADA or IFX as first antiTNF agents. Those receiving IFX did not have significantly superior outcomes compared to clinically similar children receiving ADA.

Risk Factors of Clinical Relapses in Pediatric Luminal Crohn's Disease: A Retrospective Cohort Study.

INTRODUCTION: There is currently little knowledge on factors associated with the relapse of Crohn's disease (CD) in children. The aims of this study were to describe the risk factors associated with relapse in pediatric CD and the changes in the relapse rate over the past decade. METHODS: Patients younger than 18 years and diagnosed between 2009 and 2019 were included in this retrospective cohort study. Clinical, endoscopic, histological, and laboratory data, as well as induction and maintenance treatments, were collected from the medical records. Survival analyses and Cox regression models were used to assess the impact of these risk factors on relapse. RESULTS: Six hundred thirty-nine patients were included. There was a decrease in the clinical relapse rate over the past decade: 70.9% of the patients diagnosed between 2009 and 2014 relapsed as compared with 49.1% of the patients diagnosed between 2015 and 2019 (P < 0.0001). The following variables were associated with clinical relapse: female sex (adjusted hazard ratio [aHR] = 1.52, P = 0.0007), exposure to oral 5-ASA (aHR = 1.44, P = 0.04), use of immunomodulatory agents compared with tumor necrosis factor-alpha inhibitors (methotrexate aHR = 1.73, P = 0.003; thiopurines aHR = 1.63, P = 0.002), presence of granulomas (aHR = 1.34, P = 0.02) and increased eosinophils on intestinal biopsies (aHR = 1.36, P = 0.02), high levels of C-reactive protein (aHR = 1.01, P < 0.0001) and fecal calprotectin (aHR = 1.08, P < 0.0001), and low serum infliximab levels (aHR = 2.32, P = 0.001). DISCUSSION: Relapse of pediatric CD has decreased in the past decade. The risk of relapse is significantly associated with clinical, endoscopic, histological, and laboratory variables and treatment strategies.

Current applications for measuring pediatric intima-media thickness.

Intima-media thickness is a known subclinical radiologic marker of the early manifestations of atherosclerotic disease. It is the thickness of the vessel wall, most often the carotid artery. Intima-media thickness is measured on conventional US manually or automatically. Other measurement techniques include radiofrequency US. Because there is variation in its measurement, especially in children, several recommendations have been set to increase the measurement's validity and comparability among studies. Despite these recommendations, several pitfalls should be avoided, and quality control should be performed to avoid erroneous interpretation. This article summarizes current literature in relation to the clinical applications for intima-media thickness measurement in children with known risk factors such as obesity, liver steatosis, hypercholesterolemia, diabetes, hypertension, systemic inflammatory diseases, cancer survival, kidney and liver transplant, and sickle cell disease or beta thalassemia major. Most potential indications for intima-media thickness measurement remain in the research domain and should be interpreted combined with other markers. The objective of diagnosing an increased intima-media thickness is to start a multidisciplinary treatment approach to prevent disease progression and its sequelae in adulthood.

Canadian Association of Gastroenterology Clinical Practice Guideline for the Medical Management of Pediatric Luminal Crohn's Disease.

BACKGROUND & AIMS: We aim to provide guidance for medical treatment of luminal Crohn's disease in children. METHODS: We performed a systematic search of publication databases to identify studies of medical management of pediatric Crohn's disease. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. We developed statements through an iterative online platform and then finalized and voted on them. RESULTS: The consensus includes 25 statements focused on medical treatment options. Consensus was not reached, and no recommendations were made, for 14 additional statements, largely due to lack of evidence. The group suggested corticosteroid therapies (including budesonide for mild to moderate disease). The group suggested exclusive enteral nutrition for induction therapy and biologic tumor necrosis factor antagonists for induction and maintenance therapy at diagnosis or at early stages of severe disease, and for patients failed by steroid and immunosuppressant induction therapies. The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy, corticosteroids for maintenance therapy, and cannabis in any role. The group was unable to clearly define the role of concomitant immunosuppressants during initiation therapy with a biologic agent, although thiopurine combinations are not recommended for male patients. No consensus was reached on the role of aminosalicylates in treatment of patients with mild disease, antibiotics or vedolizumab for induction or maintenance therapy, or methotrexate for induction therapy. Patients in clinical remission who are receiving immunomodulators should be assessed for mucosal healing within 1 year of treatment initiation. CONCLUSIONS: Evidence-based medical treatment of Crohn's disease in children is recommended, with thorough ongoing assessments to define treatment success.

Natural history of gastroesophageal reflux in infancy: new data from a prospective cohort.

BACKGROUND: Gastroesophageal reflux (GER) is common in infants. Gastroesophageal reflux disease (GERD) is defined as GER leading to troublesome symptoms that affect daily functioning and/or complications. This study is aimed at determining the prevalence and progression of GER and GERD in a cohort of healthy term infants from birth to 12 months old. METHODS: We conducted a prospective cohort study including all full-term living neonates born at Besançon Teaching Hospital, France. Parents completed a clinical report form and the Infant Gastroesophageal Reflux Questionnaire-Revised (I-GERQ-R) at 1, 3, 6, 10, and 12 months of age. GER was defined as score ≥ 1 to the first question with I-GERQ-R score < 16, and GERD as score ≥ 1 to the first question with I-GERQ-R score ≥ 16. Regurgitation was based on the answer to the first question of the I-GERQ-R as anything coming out of the mouth daily. RESULTS: 157/347 births were included (83 boys). The prevalence of regurgitation at least once a day was 45.7% overall. In total: 72, 69, 56, 18, and 13% of infants regurgitated at least once a day at 1, 3, 6, 10, and 12 months of age, respectively. Physiological GER affected 53, 59, 51, 16, and 12% of infants; GERD, 19, 9, 5, 2, and 2%, respectively. Two risk factors were identified: family history of GER and exposure to passive smoking. Treatment included dietary modification (14%) and pharmacotherapy (5%). CONCLUSION: Physiological GER peaked at 3 months, GERD at 1 month. Most cases resolved on their own. GER and GERD are very common in the infant's population and parents should be reassured/educated regarding symptoms, warning signs, and generally favorable prognosis. I-GERQ-R is useful to the clinical screening and follow up for GER and GERD.

Phenotypic and Functional Changes in Peripheral Blood Natural Killer Cells in Crohn Disease Patients.

We investigated activation status, cytotoxic potential, and gut homing ability of the peripheral blood Natural Killer (NK) cells in Crohn disease (CD) patients. For this purpose, we compared the expression of different activating and inhibitory receptors (KIR and non-KIR) and integrins on NK cells as well as their recent degranulation history between the patients and age-matched healthy controls. The study was conducted using freshly obtained peripheral blood samples from the study participants. Multiple color flow cytometry was used for these determinations. Our results show that NK cells from treatment-naïve CD patients expressed higher levels of activating KIR as well as other non-KIR activating receptors vis-à-vis healthy controls. They also showed increased frequencies of the cells expressing these receptors. The expression of several KIR and non-KIR inhibitory receptors tended to decrease compared with the cells from healthy donors. NK cells from the patients also expressed increased levels of different gut-homing integrin molecules and showed a history of increased recent degranulation events both constitutively and in response to their in vitro stimulation. Furthermore, treatment of the patients tended to reverse these NK cell changes. Our results demonstrate unequivocally, for the first time, that peripheral blood NK cells in treatment-naïve CD patients are more activated and are more poised to migrate to the gut compared to their counterpart cells from healthy individuals. Moreover, they show that treatment of the patients tends to normalize their NK cells. The results suggest that NK cells are very likely to play a role in the immunopathogenesis of Crohn disease.

Skin Manifestations in Pediatric Patients Treated With a TNF-Alpha Inhibitor for Inflammatory Bowel Disease: A Retrospective Study [Formula: see text].

BACKGROUND: Tumor necrosis factor (TNF) alpha inhibitors (anti-TNF) are effective in the treatment of inflammatory bowel disease (IBD) as well as psoriasis. Their increasing use has raised the identification of cutaneous side effects (CSEs). Evidence in children is limited. OBJECTIVES: The objective of this study is to describe CSEs of anti-TNF treatment in a pediatric population with IBD. METHODS: This is a retrospective single-center study of children with IBD under anti-TNF treatment between 2013 and 2016. A total of 40 patients with CSEs related to anti-TNF were referred to our pediatric dermatology clinic. A control group was randomly selected from patients receiving anti-TNF for IBD, who were referred to the dermatology clinic for other conditions unrelated to anti-TNF. RESULTS: Of 343 patients with IBD, 40 (11.3%) presented CSEs potentially related to the treatment. No differences in sex, age, and underlying disease were found between those with and without CSEs. The most frequent CSEs were psoriasiform eruptions (41%) which were more exudative than usual, located especially in skin folds and on the scalp; skin infections (20%); and eczematous eruptions (10%). Only 5% of patients changed or discontinued the current anti-TNF because of CSEs. CONCLUSION: This is one of the largest pediatric cohorts of IBD patients with CSEs. Psoriasiform eruptions were the most common CSEs, with predilection for skin folds and scalp, and frequent superimposed bacterial infection. Topical and/or systemic antibiotics were required in addition to topical corticosteroids in 25% of patients. The rate of discontinuation of anti-TNF therapy due to CSEs was low.

Should Proton Pump Inhibitors be Systematically Prescribed in Patients With Esophageal Atresia After Surgical Repair?

OBJECTIVE: To evaluate outcomes of patients with esophageal atresia (EA) on systematic treatment with proton pump inhibitors (PPI) since the neonatal period and to determine factors associated with successful discontinuation of PPI. STUDY DESIGN: Longitudinal cohort study with prospective data collection of 73 EA patients, over 11 years systematically treated with PPI. Outcome and predictive factors for discontinuation of PPI treatment were evaluated at study end in February 2017. The incidence of anastomotic strictures was compared with a historical cohort of 134 EA patients followed in the same institution between 1990 and 2005 before the era of systematic PPI treatment. RESULTS: PPI treatment was discontinued definitively in 48% of patients during follow-up. Prematurity, longer initial hospitalization, moderate-to-severe tracheomalacia, anastomotic leak and anastomotic stricture had a significant negative association with PPI discontinuation on univariate analysis (P < 0.05). On adjusted multivariable Cox regression analysis, moderate-to-severe tracheomalacia and anastomotic leak were negatively associated with discontinuation of PPI treatment (hazard ratio 0.26 [95% CI 0.12-0.59]; P = 0.001 and hazard ratio 0.38 [95% CI 0.16-0.93]; P = 0.03, respectively). There was no significant difference in the incidence of anastomotic strictures in the present cohort compared with the historical cohort (44% vs 39%); (P > 0.05). CONCLUSIONS: PPI treatment does not prevent the formation of anastomotic strictures and appears to be over-prescribed in children with airway symptoms because of tracheomalacia. This suggests that PPI treatment could be prescribed more selectively. Close monitoring and long-term follow-up, however, of these vulnerable patients in specialized multidisciplinary clinics is imperative.

Prenatal vitamin D status and offspring's growth, adiposity and metabolic health: a systematic review and meta-analysis.

In this systematic review and meta-analysis of observational studies, we aimed to estimate the associations between prenatal vitamin D status and offspring growth, adiposity and metabolic health. We searched the literature in human studies on prenatal vitamin D status and offspring growth in PubMed, up to July 2017. Studies were selected according to their methodological quality and outcomes of interest (anthropometry, fat mass and diabetes in offspring). The inverse variance method was used to calculate the pooled mean difference (MD) with 95 % CI for continuous outcomes, and the Mantel-Haenszel method was used to calculate the pooled OR with 95 % CI for dichotomous outcomes. In all, thirty observational studies involving 35 032 mother-offspring pairs were included. Vitamin D status was evaluated by circulating 25-hydroxyvitamin D (25(OH)D) level. Low vitamin D status was based on each study's cut-off for low 25(OH)D levels. Low prenatal vitamin D levels were associated with lower birth weight (g) (MD -100·69; 95 % CI -162·25, -39·13), increased risk of small-for-gestational-age (OR 1·55; 95 % CI 1·16, 2·07) and an elevated weight (g) in infant at the age of 9 months (g) (MD 119·75; 95 % CI 32·97, 206·52). No associations were observed between prenatal vitamin D status and other growth parameters at birth, age 1 year, 4-6 years or 9 years, nor with diabetes type 1. Prenatal vitamin D may play a role in infant adiposity and accelerated postnatal growth. The effects of prenatal vitamin D on long-term metabolic health outcomes in children warrant future studies.

Serological markers predict inflammatory bowel disease years before the diagnosis.

OBJECTIVE: Anti-neutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae mannan antibodies (ASCAs) have been detected in the serum of patients with ulcerative colitis (UC) and Crohn's disease (CD) and their unaffected family members. The aim of this study was to establish the value of serological markers as predictors of UC and CD. DESIGN: Individuals who developed CD or UC were identified from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. At recruitment, none of the participants had a diagnosis of CD or UC. For each incident case, two controls were randomly selected matched for centre, date of birth, sex, date of recruitment and time of follow-up. Serum of cases and controls obtained at recruitment were analysed for ASCA IgG, ASCA IgA, perinuclear anti-neutrophil cytoplasmic antibody (pANCA), antibodies against Escherichia coli outer membrane porin C (OmpC) and flagellin CBir1. Conditional logistic regression was used to determine risk of CD and UC. Receiver operating characteristic curves were constructed to test accuracy. RESULTS: A total of 77 individuals were diagnosed with CD and 167 with UC after a mean follow-up of 4.5 (SD 3.2) and 4.4 (SD 3.1) years following blood collection, respectively. Combinations of pANCA, ASCA, anti-CBir1 and anti-OmpC were most accurate in predicting incident CD and UC (area under curve 0.679 and 0.657, respectively). The predictive value of the combination of markers increased when time to diagnosis of CD or UC decreased. CONCLUSION: A panel of serological markers is able to predict development of CD and UC in individuals from a low-risk population.

Outcomes of Premature Infants With Type C Esophageal Atresia.

BACKGROUND: To review the outcomes of premature patients with type C esophageal atresia (EA). METHODS: In this retrospective cohort study, charts of patients of type C EA patients were reviewed from 1992 to 2022. Outcomes of premature patients were compared to term patients. Preterm patients were analyzed to compare outcomes of infants with very low birth weights (VLBW) to patients >1,500 g as well as primary versus delayed anastomosis. RESULTS: Among 192 type C EA, 67 were premature. Median and interquartile range (IQR) gestational age and birth weight of preterm patients were 34 [33-36] weeks and 1965 [1740-2290] g. Delayed anastomosis was performed in 12 (18%) preterm vs. 3 (2%) term patients (p = 0.0003). Short-term postoperative outcomes were similar between preterm and term patients, except for recurrent fistula (16% vs. 6%, p = 0.01). Prematurity was associated with an increased need for long-term enteral tube feeding (56% vs. 10%, p = 0.0001) and parenteral nutrition (10 days vs. 0 days, p = 0.0004). The length of stay was 3 times longer when patients were premature (50 days vs. 17 days, p = 0.002). Delayed surgery in preterm patients was associated with post-operative leaks, strictures, recurrent fistula, prolonged enteral tube feeding, and gastrostomy insertion. Patients with very low birth weight (VLBW) were compared to other preterm patients and showed no difference in terms of rate of delayed surgery, and post-operative outcomes. CONCLUSION: Despite increased prematurity-related comorbidities and low birth weight, premature infants with type C EA/TEF have similar post-operative outcomes to term patients though recurrent fistula was more frequent with prematurity. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: III.

Effects of polyphenol supplementation on hepatic steatosis, intima-media thickness and non-invasive vascular elastography in obese adolescents: a pilot study protocol.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent in obese adolescents. Increased systemic inflammation and decreased gut microbial diversity linked to obesity affect the liver and are also associated with cardiovascular diseases in adulthood. However, NAFLD and vascular alterations are reversible. METHODS AND ANALYSIS: This pilot study evaluated the feasibility of a prospective open-label randomised controlled trial evaluating the effects of polyphenols on NAFLD and vascular parameters in obese adolescents. Children aged 12-18 years with hepatic steatosis (n=60) will be recruited. The participants will be randomised with a 1:1 allocation ratio to receive polyphenol supplementation one time per day for 8 weeks along with the clinician-prescribed treatment (group B, n=30) or to continue the prescribed treatment without taking any polyphenols (group A, n=30). The outcome measures will be collected from both the groups at day 1 before starting polyphenol supplementation, at day 60 after 8 weeks of supplementation and at day 120, that is, 60 days after supplementation. The changes in hepatic steatosis and vascular parameters will be measured using liver and vascular imaging. Furthermore, anthropometric measures, blood tests and stool samples for gut microbiome analysis will be collected. After evaluating the study's feasibility, we hypothesise that, as a secondary outcome, compared with group A, the adolescents in group B will have improved NAFLD, vascular parameters, systemic inflammation and gut microbiome. ETHICS AND DISSEMINATION: This study is approved by Health Canada and the hospital ethics. Participants and their parents/tutors will both provide consent. Trial results will be communicated to the collaborating gastroenterologists who follow the enrolled participants. Abstracts and scientific articles will be submitted to high-impact radiological societies and journals. CLINICALTRIALS: gov ID: NCT03994029. Health Canada authorisation referral number: 250 811. Protocole version 13, 2 June 2023. TRIAL REGISTRATION NUMBER: NCT03994029.

Phenotype and outcomes of very early onset and early onset inflammatory bowel diseases in a Montreal pediatric cohort.

Objectives: The incidence of very-early-onset inflammatory bowel disease (VEO-IBD) and early-onset IBD (EO-IBD) is increasing. Here, we report their phenotype and outcomes in a Montreal pediatric cohort. Methods: We analyzed data from patients diagnosed with IBD between January 2014 and December 2018 from the CHU Sainte-Justine. The primary endpoint was to compare the phenotypes of VEO-IBD and EO-IBD. The secondary endpoints involved comparing outcomes and rates of steroid-free clinical remission (SFCR) at 12 (±2) months (m) post-diagnosis and at last follow-up. Results: 28 (14 males) and 67 (34 males) patients were diagnosed with VEO-IBD and EO-IBD, respectively. Crohn's disease (CD) was more prevalent in EO-IBD (64.2% vs. 39.3%), whereas unclassified colitis (IBD-U) was diagnosed in 28.6% of VEO-IBD vs. 10.4% of EO-IBD (p < 0.03). Ulcerative colitis (UC) and IBD-U predominantly presented as pancolitis in both groups (VEO-IBD: 76.5% vs. EO-IBD: 70.8%). Combining all disease subtypes, histological upper GI lesions were found in 57.2% of VEO-IBD vs. 83.6% of EO-IBD (p < 0.009). In each subtype, no differential histological signature (activity, eosinophils, apoptotic bodies, granulomas) was observed between both groups. At 12 m post-diagnosis, 60.8% of VEO-IBD and 62.7% of EO-IBD patients were in SFCR. At a median follow-up of 56 m, SFCR was observed in 85.7% of VEO-IBD vs. 85.0% of EO-IBD patients. Conclusion: The rate of patients in SFCR at 1-year post-diagnosis and at the end of follow-up did not significantly differ between both groups.

Inflammatory Bowel Disease Among Canadian Children: Comparison Between Children of Non-European Descent and Children of European Descent.

BACKGROUND: Inflammatory bowel disease (IBD) phenotypes may differ between countries and ancestral groups. The study aim was to examine ancestry and subtype variations of children newly diagnosed with IBD. METHODS: Children newly diagnosed with IBD enrolled into the Canadian Children Inflammatory Bowel Disease Network inception cohort study were categorized into 8 ancestral groups. Prospectively collected data at diagnosis and follow-up were compared between ancestral groups. RESULTS: Among 1447 children (63.2% Crohn's disease, 30.7% ulcerative colitis), 67.8% were European, 9.4% were South Asian, 3.8% were West Central Asian and Middle Eastern, 2.3% were African, 2.2% were East/South East Asian, 2.0% were Caribbean/Latin/Central/South American, 9.9% were mixed, and 2.6% were other. Children of African descent with ulcerative colitis had an older age of diagnosis compared with children of European descent (median 15.6 years vs 13.3 years; P = .02). Children of European descent had a higher proportion of positive family history with IBD (19.3% vs 12.1%; P = .001) compared with children of non-European descent. Children of European descent also had a lower proportion of immigrants and children of immigrants compared with children of non-European descent (9.8% vs 35.9%; P < .0001; and 3.6% vs 27.2%; P < .0001, respectively) . CONCLUSIONS: Important differences exist between different ancestral groups in pediatric patients with IBD with regard to age of diagnosis, family history, and immigrant status. Our study adds to the knowledge of the impact of ancestry on IBD pathogenesis.

This study explores the ancestral and phenotypic variation of Canadian children newly diagnosed with inflammatory bowel disease. It identifies differences between children of European and non-European descent in phenotypes of inflammatory bowel disease, disease location and behavior, family history, and immigrant status.

Appendectomy and risk for inflammatory bowel disease: effect of age and time post appendectomy - a cohort study.

BACKGROUND AND OBJECTIVE: Appendectomy may modulate the risk of inflammatory bowel disease through an effect on the gut microbiota. This study investigated the associations between appendectomy and incidence of Crohn's disease (CD) or ulcerative colitis (UC), with an emphasis on the influence of age and time post appendectomy. METHODS: This cohort study included 400 520 subjects born in Québec in 1970-1974 and followed until 2014. Administrative health data were used to ascertain appendectomy and cases of CD and UC. Cox proportional hazards models with time-dependent variables (appendectomy and time elapsed post appendectomy) allowed for the estimation of HRs and 95% CIs. RESULTS: A total of 2545 (0.6%) CD cases and 1134 (0.3%) UC cases were identified during follow-up. Appendectomy increased the risk of CD (HR=2.02; 95% CI: 1.66 to 2.44), especially when performed at 18-29 years of age. The risk of CD was increased in the first 2 years, and decreased significantly after ≥15 years post appendectomy. Appendectomy appeared to protect against UC (HR=0.39; 95% CI: 0.22 to 0.71). The risk of UC was not associated with age at appendectomy, but decreased with time elapsed post appendectomy (HR=0.21; 95% CI: 0.06 to 0.72, comparing ≥5 with 0-4 years after appendectomy). CONCLUSIONS: The increased risk of CD related to appendectomy in young adults may result from detection bias, but physicians should have a low threshold for suspicion of CD in young symptomatic adults with a history of appendectomy. A strong protective effect of appendectomy against UC was observed after 5 years.

Epstein-Barr virus seroprevalence and viral load at disease onset in children with inflammatory bowel disease.

Background and Aim: Patients with inflammatory bowel disease (IBD) are at increased risk for life-threatening complications of Epstein-Barr virus (EBV), including lymphoproliferative diseases. These complications are likely related to inherent immune dysfunction and immunomodulating therapies often used. We aimed to determine the seroprevalence of EBV at diagnosis in our population, its impact on disease at onset, and the risk of active EBV infection. Methods: We included patients newly diagnosed with IBD for whom an EBV serology was performed over a 2-year period. Demographic information and data on disease characteristics were collected retrospectively. Stored serum from the time of diagnosis was retrieved when available for the patients with positive EBV serology, and quantitative polymerase chain reaction testing was performed to assess the pre-treatment viral load of EBV. Results: One hundred twenty patients were included in the study. Fifty-three patients (44.2%) had positive EBV serology at diagnosis. Stratified by age group, the prevalence of seropositive patients was for 0 to <10 years 35%, 10 to <17 years 46%, and ≥17 years 50%. Overall, therapies started within 6 months of diagnosis were similar in both the seropositive and seronegative groups. Within the seropositive group, 66% received systemic corticosteroids, 32.1% infliximab, 5.7% adalimumab, and 5.7% azathioprine. Conclusion: EBV seroprevalence is high in pediatric patients with IBD. EBV seropositivity did not seem to influence the severity of disease at onset or initial choice of therapy.

Benchmark of Data Processing Methods and Machine Learning Models for Gut Microbiome-Based Diagnosis of Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) wait months and undergo numerous invasive procedures between the initial appearance of symptoms and receiving a diagnosis. In order to reduce time until diagnosis and improve patient wellbeing, machine learning algorithms capable of diagnosing IBD from the gut microbiome's composition are currently being explored. To date, these models have had limited clinical application due to decreased performance when applied to a new cohort of patient samples. Various methods have been developed to analyze microbiome data which may improve the generalizability of machine learning IBD diagnostic tests. With an abundance of methods, there is a need to benchmark the performance and generalizability of various machine learning pipelines (from data processing to training a machine learning model) for microbiome-based IBD diagnostic tools. We collected fifteen 16S rRNA microbiome datasets (7,707 samples) from North America to benchmark combinations of gut microbiome features, data normalization and transformation methods, batch effect correction methods, and machine learning models. Pipeline generalizability to new cohorts of patients was evaluated with two binary classification metrics following leave-one-dataset-out cross (LODO) validation, where all samples from one study were left out of the training set and tested upon. We demonstrate that taxonomic features processed with a compositional transformation method and batch effect correction with the naive zero-centering method attain the best classification performance. In addition, machine learning models that identify non-linear decision boundaries between labels are more generalizable than those that are linearly constrained. Lastly, we illustrate the importance of generating a curated training dataset to ensure similar performance across patient demographics. These findings will help improve the generalizability of machine learning models as we move towards non-invasive diagnostic and disease management tools for patients with IBD.

A qualitative study of adolescents and young adults' experience and perceived needs during the first wave of the COVID-19 pandemic.

AIMS: COVID-19 has led to unprecedented public health measures such as school and university closures across the world. While initial surveys show an increase in anxiety, we have little information on the subjective experience of adolescents and young adults (AYAs). The aims of this study were to understand the lived experience and needs of AYAs related to home confinement and preventive measures due to COVID-19. DEMOGRAPHICS AND SETTINGS: A total of 25 AYAs (13-24 years old) with diverse gender, age, or health conditions, living in Québec (Canada), were interviewed in May 2020, during the COVID-19 home confinement period. METHODOLOGY: Four virtual focus groups were held via a virtual video-conferencing platform (Zoom©). Thematic analysis was conducted. RESULTS: Thematic analysis revealed five main themes: (1) challenges and opportunities related to the experience of home confinement; (2) variable risk perception of COVID-19 infection; (3) development of coping strategies to maintain well-being; (4) need for information and accompaniment; (5) apprehensions related to perceptions of the future. CONCLUSION: AYAs did not feel considered in public health decisions, fostering an increase in anxiety, especially in more vulnerable AYAs living with chronic diseases.

Changes in the clinical phenotype and behavior of pediatric luminal Crohn's disease at diagnosis in the last decade.

BACKGROUND AND AIMS: The aims of this study were to describe the trends in the behavior of pediatric CD during the last decade and to describe the seasonal variation of disease presentation. METHODS: Patients under 18 years old and diagnosed between 2009 and 2019 were included. The clinical, endoscopic, histological, and laboratory data were collected from the medical records. We analyzed the trends of these parameters according to the year and season of diagnosis. RESULTS: 654 patients were included in the study. The number of incident CD cases increased yearly. Patients diagnosed between 2015 and 2019 were younger at diagnosis (OR 2.53, p = 0.02), had more perianal diseases (OR: 2.30, p < 0.0001) and more granulomas (OR: 1.61, p = 0.003), but fewer eosinophils (OR: 0.35, p < 0.0001) and less chronic lymphoplasmacytic infiltrate (OR: 0.56, p = 0.008) as compared to the 2009-2014 cohort. There was fewer CD diagnosis during winter. Patients diagnosed in the fall had lower PCDAIs, less failure to thrive and less extensive digestive involvement. Colonic disease was significantly more frequent during summer and fall. CONCLUSION: The clinical and histological phenotype of CD has changed over time and there are important seasonal trends in the frequency and severity on disease behavior suggesting possible disease triggers.

Canadian Consensus Statements on the Transition of Adolescents and Young Adults with Inflammatory Bowel Disease from Pediatric to Adult Care: A Collaborative Initiative Between the Canadian IBD Transition Network and Crohn's and Colitis Canada.

Objectives: With the increased prevalence of childhood-onset inflammatory bowel disease (IBD), there is a greater need for a planned transition process for adolescents and young adults (AYA). The Canadian IBD Transition Network and Crohn's and Colitis Canada joined in collaborative efforts to describe a set of care consensus statements to provide a framework for transitioning AYA from pediatric to adult care. Methods: Consensus statements were drafted after focus group meetings and literature reviews. An expert panel consisting of 20 IBD physicians, nurses, surgeon, adolescent medicine physician, as well as patient and caregiver representatives met, discussed and systematically voted. The consensus was reached when greater than 75% of members voted in agreement. When greater than 75% of members rated strong support, the statement was rendered a strong recommendation, suggesting that a clinician should implement the statement for all or most of their clinical practice. Results: The Canadian expert panel generated 15 consensus statements (9 strong and 6 weak recommendations). Areas of focus of the statements included: transition program implementation, key stakeholders, areas of potential need and gaps in the research. Conclusions: These consensus statements provide a framework for the transition process. The quality of evidence for these statements was generally low, highlighting the need for further controlled studies to investigate and better define effective strategies for transition in pediatric to adult IBD care.