We conducted a nationwide survey using a validated Gastrointestinal Health Questionnaire (GHQ) for Rett syndrome (RTT) to provide an updated and accurate baseline assessment of the prevalence of common gastrointestinal (GI) issues in RTT, based on parental reporting. Parents and caregivers of females with RTT or normally developing, unaffected, age-matched controls completed the GHQ survey. The prevalence of GI symptoms and personality and mood symptoms due to stomach or intestinal problems, as well as GI medication usage and surgical interventions, were assessed in females with RTT and unaffected controls. The relation between GI symptoms and medication usage, surgical status, age, and genetic mutation were analyzed. Parents of 118 females with RTT and 27 unaffected females completed the GHQ. GI symptoms were common in females with RTT, including constipation (81%), gas and bloating (70%), issues with eating, chewing and swallowing (73%), and irritability because of stomach or intestinal problems (53%). Females with RTT commonly used proton pump inhibitors (52%) and laxatives (64%). Medication usage was associated with significantly higher GHQ symptom scores. Parents of individuals with RTT reported a significantly higher prevalence of GI symptoms affecting their daughters in all symptom categories compared with unaffected females. GI problems are common in RTT and pose a significant medical burden to caregivers. The GHQ is a useful tool to assess GI issues in individuals with RTT. Improved recognition of these issues may allow for improved treatment and enhanced quality of life for girls and women affected by RTT.

Acid blocker therapy (ABT) has become common in cystic fibrosis (CF), despite insufficient evidence for benefits and studies showing potentially negative effects. We examined associations between ABT usage and growth, gut microbiome (GM), and early-onset lung disease in young children with CF. One hundred forty-five infants with CF born during 2012-2017, diagnosed through newborn screening by age 3 months and followed to 36 months of age at six CF centers were evaluated. Longitudinal data on growth, pancreatic functional status, pulmonary symptoms, and acid blocker medications were prospectively collected. Early-onset lung disease severity was evaluated by a clinical scoring system. GM composition was assessed by 16S rRNA methodology. ABT use before age 3 years was frequent, with 81 (56%) of patients on H2 receptor antagonist (H2RA) or proton pump inhibitor (PPI), and higher among pancreatic insufficient (60%) versus pancreatic sufficient (26%) children. H2RA was commonly prescribed in infancy before transitioning to PPI. Growth improvements were not significantly greater, while GM α-diversity at 3 years of age was significantly lower and early-onset lung disease more severe, in persistent ABT users compared to nonusers of ABT. In our cohort of young children with CF, early and persistent ABT use was not associated with significant growth benefits and instead showed associations with reduced GM diversity and negative effects on early-onset lung disease. Consequentially, there is a critical need for systematic evaluation and comprehensive risk-benefit analysis of ABT to ensure proper guidelines for children with CF.

Celiac disease (CD) is an autoimmune gastrointestinal disorder that requires a strict lifelong gluten-free diet (GFD). Gluten-free (GF) foods are more expensive and less readily accessible than gluten-containing foods, contributing to an increased risk for food insecurity (FI). The study aimed to determine associations between GF-FI, sociodemographic risk factors and child dietary adherence and diet quality (DQ). A 26-item, cross-country online survey was administered through social media to parents of children with CD on the GFD. The survey elicited household and CD child sociodemographic and clinical characteristics (e.g., duration of CD), measures of household FI, child DQ and GFD adherence, and parents' concerns related to GF food. Household GF-FI was evaluated using the validated Hunger Vital Sign™ and the US Department of Agriculture Six-Item Short Form Household Food Security Survey Module. GF-FI occurred in 47% of households with children with CD with >30% reporting low to very low food security. Sociodemographic risk factors identified included lower income, renters, rural residency, single-parental households, and having children with additional dietary restrictions (p < 0.001). Regardless of FI status, a majority of households reported experiencing significantly higher GF food expenditure. GF-FI was associated with reduced adherence to the GFD, increased consumption of processed GF food, and lower intakes of fresh fruits and vegetables and GF grains among children with CD (p < 0.05). GF-FI is prevalent in this multiethnic cohort of households with CD children and is associated with worsening DQ and GFD adherence. Policy interventions are urgently needed to address GF-FI.

The role of nutrition in the recovery of critically ill children has not been investigated and current nutrition provision in the post-pediatric intensive care unit (PICU) period is unknown. The primary objective of this study was to describe ward nutrition support in children following PICU discharge. Children up to 18 years admitted to one of nine PICUs over a 2-week period with a length of stay >48 h were enrolled. Data were collected on the first full ward day following PICU discharge and on Days 7, 14, 21, and 28 following PICU admission. Data points included oral intake, enteral (EN) and parenteral nutrition (PN) support, and oral and EN energy and protein provision. Among the 108 children, on the first full ward day 75/108 (69%) children received EN, 54/108 (50%) oral intake, and 8/108 (7%) PN. Of those receiving oral nutrition only on the first full ward day (25/108; 23%), 9/25 (36%) received <50% of their estimated energy and protein requirements. Of those provided EN only, and where nutrition targets were known, on the first full ward day 8/46 (17%) and 7/46 (15%) met <75% of their estimated energy and protein requirements, respectively. On Day 28, this increased to 4/12 (33%) and 5/12 (42%). In this study of ward-based nutrition support, key findings included consistent use of EN and PN up to at least 28 days following PICU admission, and a high proportion of children receiving EN or oral intake only not meeting their estimated energy and protein requirements.

Ubiquitin-specific protease 53 (USP53) is essential for formation of cellular tight junctions and variations in this gene disrupt the tight junctions, resulting in cholestasis. We describe the clinical manifestations and outcomes of patients with USP53 mutations from the Indian progressive familial intrahepatic cholestasis registry. All 29 patients who harbored mutations in the USP53 gene either in the homozygous, compound heterozygous, or heterozygous state and presented with cholestasis were included. USP53 variants related to cholestasis had good outcomes, with native liver survival in 82.7%, whereas 17.3% required liver transplantation. Jaundice developed in 93% and within 3 months of age in 48.8%. Jaundice resolved in 21 (72.4%). Pruritus 76% at a median age of 7 months (severe in 10/22, 45% and refractory to medical therapy in 4, 18.1%). Majority of them (82.7%) had biallelic mutations. Protein-truncating mutations were present in 20 (69%) and missense mutations in 9 (31%). No correlation was found between the genotype and the outcome.

Survival rates in children born with esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) have improved; however, morbidity associated with the disease remains high. This study aimed to assess the prevalence of gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), fungal esophagitis, esophageal strictures, and long-term outcomes in children with EA/TEF. We conducted a retrospective chart review on patients with EA/TEF who were seen at Children's Wisconsin from January 2003 to January 2023. Patients born with EA/TEF were included if they underwent at least one endoscopy after 1 year of age. GERD was diagnosed based on abnormal findings on endoscopy, pH-metry, and/or history of fundoplication. EoE and fungal esophagitis were diagnosed based on abnormal endoscopy. Esophageal stricture diagnosis was based on findings on endoscopy and/or esophagram, and clinical symptoms necessitating esophageal dilation. Eighty-five patients (64.7% males, mean age 7.5 years) were included, the majority had type C EA/TEF (90.6%). GERD was diagnosed in 61.1% (n = 52), 49.4% (n = 42) by macro and/or microscopic endoscopic findings, 22.3% (n = 19) by abnormal pH-metry, and 21.1% (n = 18) by the need for fundoplication for refractory reflux and/or esophageal stricture. Risk of GERD increased with lower gestational age (p = 0.0030), lower birth weight (p = 0.023), and long-gap EA (p = 0.034). In children diagnosed with GERD, only 13.4% of patients (n = 7/52) were able to be weaned off proton pump inhibitor (PPI) without disease recurrence. However, overall, at the completion of the study, 44.7% (n = 38) of patients were successfully weaned off PPI without evidence of GERD. EoE was diagnosed in 20% of the patients (n = 17). All patients diagnosed with EoE required escalation of therapy from PPI alone to swallowed corticosteroids in 52.9% (n = 9), dupilumab in 23.5% (n = 4), elemental formula in 17.6% (n = 3), and elemental formula and swallowed steroids in 5.8% (n = 1). Fungal esophagitis was diagnosed in 15.3% of patients (n = 13). An esophageal stricture requiring dilation was diagnosed in 77.6% (n = 66) of patients at a mean age of 28.5 months, with over 60% diagnosed by 24 months of age. Children born with EA/TEF continue to be at high risk of developing GERD, EoE, fungal esophagitis, and esophageal stenosis. Diagnostic and therapeutic endoscopy remains a high-yield test to identify and treat these comorbidities.

Vedolizumab and ustekinumab are effective in inducing and maintaining corticosteroid-free clinical remission (CFR) in adult patients with inflammatory bowel disease (IBD). This study describes the efficacy and safety of vedolizumab and ustekinumab in pediatric IBD. All patients ≤18 years of age with Crohn's disease (CD) or ulcerative colitis (UC) treated with vedolizumab or ustekinumab in three centers in Northern France were followed retrospectively. The primary outcome was CFR at Week 14 (W14). Twenty-five patients (9 CD, 16 UC) and 33 patients (28 CD, 5 UC) were started on vedolizumab and ustekinumab respectively between 2016 and 2021. All were previously treated with antitumor necrosis factor (TNF). The median time from diagnosis to treatment initiation was 21.0 (12.0-44.0) and 42.0 (22.0-73.5) months for vedolizumab and ustekinumab respectively. Among vedolizumab-treated patients, 36% were in CFR at W14, including 22% in CD and 44% in UC. At W52, 56% were in CFR, including 33% in CD and 69% in UC. Among ustekinumab-treated patients, 49% were in CFR at W14, including 54% in CD and 20% in UC. At W52, 55% were in CFR, including 57% in CD and 40% in UC. There was a significant increase in median growth velocity between W0 and W52 of +2 SD in vedolizumab-treated patients (p = 0.0002). Four adverse events were reported during vedolizumab treatment, none for ustekinumab-treated patients. Vedolizumab and ustekinumab appear to be effective in inducing and maintaining CFR in pediatric-onset IBD. Randomized controlled trials are needed to confirm these results.

The data on the usefulness of DQ-typing in screening for celiac disease (CD) among type 1 diabetic (T1D) patients came from the West. We conducted this study among T1D patients to: (1) determine the frequency of DQ-genotypes, (2) assess the risk associated with human leukocyte antigen (HLA)-DQ genotypes, and (3) identify the cost-effective screening strategy. HLA-DQ genotyping was performed on 67 T1D patients with CD (cases) (mean age 15 years) and 224 T1D patients without CD (controls) (mean age 18.29 years) (2021-2023). The entry criterion for the control group was duration of T1D ≥5 years and negative annual celiac serology assay. On comparison of the cases versus controls, T1D patients carrying homozygous DQ2.5 genotype (30% vs. 13.8%) or DR3-DQ2.5 haplotype (81.3% vs. 65.7%) showed significantly "higher risk" (odds ratio [OR] = 2.64, p = 0.002; OR = 2.3, p = 0.008, respectively) to develop CD. Only 4% do not harbor any of the CD-at risk genotypes (DQ2.5, DQ8, or DQ2.2) and none developed CD. Heterozygous DQ8 was associated with a significantly lower risk of developing CD with OR of 0.123 (1.5% in cases vs. 10.3% in controls, p = 0.022). Only 4% of Saudi patients with T1D carry DQ-genotypes at no risk to develop CD, which supports the European guidelines that recommend celiac serology test as the most cost-effective screening method. We identified the risk gradient associated with DQ-genotypes to develop CD in our population which could help in counseling patients for the risk to develop CD and planning follow-up serology tests.

Colonoscopy is performed for diagnostic and therapeutic purposes. The quality of colonoscopy depends on adequate bowel cleansing. However, there is no standardized protocol for bowel preparation in children. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to estimate the effectiveness, safety, and tolerability profile of polyethylene glycol (PEG) compared with those of sodium picosulfate (SPMC) in children. The primary sources of the reviewed studies were Scopus, PubMed, and Cochrane Library. The databases were systematically searched for RCTs comparing PEG 4000 to SPMC as a bowel cleansing solution. Six studies were included. The analysis showed that both PEG and SPMC are effective for bowel cleansing, while a split-dose regimen may be preferable to a day-before one. There were no differences between the two groups regarding adverse events such as abdominal pain, nausea, vomiting, bloating, and anal discomfort. Additionally, preparation with SPMC was preferred in terms of acceptability and compliance. Still, the need to place a nasogastric tube was significantly lower in the SPMC group compared to the PEG group and in the split dose regimen compared to the day before. In conclusion, PEG and SPMC are equally effective in obtaining an adequate bowel cleansing with a comparable adverse event rate; moreover, split-dose administration may be preferable to day-before one in terms of effective bowel cleansing. However, SPMC preparation is more acceptable seems to result in higher compliance, and to reduce the use of a nasogastric tube, that we encounter daily in clinical practice, is perceived as a stressful experience for children and their families.

The no-biopsy approach to diagnose celiac disease (CD), introduced in the 2012 European Society for Gastroenterology and Hepatology and Nutrition guidelines, requires an anti-endomysial antibody (EMA) confirmatory serology test following a high-positive immunoglobulin A anti-tissue transglutaminase-2 (anti-TG2) antibody ≥10 times the upper limit of normal (ULN). The aim of this retrospective study is to compare EMA positivity and high-positive anti-TG2 in patients who had their confirmatory test within two month of their first high-positiveanti-TG2 test. Among 933 patients who had high-positive anti-TG2 serology more than 10 times the ULN in their first sample, all had both high-positive anti-TG2 and positive EMA, most of them with very high EMA titers (99.6%) in their confirmatory test. In conclusion, we suggest that a repeated anti-TG2 test can replace the EMA test as the confirmatory serology test for the confirmation of the diagnosis of CD in the no-biopsy approach.