Next-generation sequencing (NGS) technologies have changed the process of genetic diagnosis from a gene-by-gene approach to syndrome-based diagnostic gene panel sequencing (DPS), diagnostic exome sequencing (DES), and diagnostic genome sequencing (DGS). A priori information on the causative genes that might underlie a genetic condition is a prerequisite for genetic diagnosis before conducting clinical NGS tests. Theoretically, DPS, DES, and DGS do not require any information on specific candidate genes. Therefore, clinical NGS tests sometimes detect disease-related pathogenic variants in genes underlying different conditions from the initial diagnosis. These clinical NGS tests are expensive, but they can be a cost-effective approach for the rapid diagnosis of rare disorders with genetic heterogeneity, such as the glycogen storage disease, familial intrahepatic cholestasis, lysosomal storage disease, and primary immunodeficiency. In addition, DES or DGS may find novel genes that that were previously not linked to human diseases.

Purpose: The long-term efficacy and safety of infliximab (IFX) in children with ulcerative colitis (UC) have not been well-evaluated. Here, we reviewed the long-term durability and safety of IFX in our single center pediatric cohort with UC. Methods: This retrospective study included 20 children with UC who were administered IFX. Results: For induction, 5 mg/kg IFX was administered at weeks 0, 2, and 6, followed by every 8 weeks for maintenance. The dose and interval of IFX were adjusted depending on clinical decisions. Corticosteroid (CS)-free remission without dose escalation (DE) occurred in 30% and 25% of patients at weeks 30 and 54, respectively. Patients who achieved CS-free remission without DE at week 30 sustained long-term IFX treatment without colectomy. However, one-third of the patients discontinued IFX treatment because of a primary nonresponse, and one-third experienced secondary loss of response (sLOR). IFX durability was higher in patients administered IFX plus azathioprine for >6 months. Four of five patients with very early onset UC had a primary nonresponse. Infusion reactions (IRs) occurred in 10 patients, resulting in discontinuation of IFX in four of these patients. No severe opportunistic infections occurred, except in one patient who developed acute focal bacterial nephritis. Three patients developed psoriasis-like lesions. Conclusion: IFX is relatively safe and effective for children with UC. Clinical remission at week 30 was associated with long-term durability of colectomy-free IFX treatment. However, approximately two-thirds of the patients were unable to continue IFX therapy because of primary nonresponse, sLOR, IRs, and other side effects.

Purpose: To assess parent perspectives of the current and potential future tests for their child with inflammatory bowel disease (IBD). Methods: New Zealand parents of a child with IBD were invited to complete an anonymous online survey. Experiences relating to their child's blood or faecal tests, medical imaging (abdominal ultrasound [US], abdominal computerised tomography [CT] and magnetic resonance enterography) and colonoscopy were collected. Perceived attitudes to potential future testing of urine, saliva, and breath, were sought. Results: Twenty-eight parents, 93% female completed the survey, and 86% were aged between 35 and 54 years. Baseline information was provided by parents for 27 of 28 children, 70.3% had Crohn's disease with a mean disease duration of 2.67 years. Blood tests were the most requested and completed tests, while CT was the least ordered and most refused test. Colonoscopy was rated as the least comfortable and generated the most worry. Explanation of test significantly improved parent's levels of understanding when their child had blood, faecal, imaging (US) or colonoscopy tests. Providing an explanation, test invasiveness and the impact of the blood results may have on their child's treatment significantly improved parents' comfort levels. However, explanation of colonoscopy generated a significant parental concerns. Saliva, urine and blood tests were chosen as the most preferred disease monitoring tests. Conclusion: Parents preferred any tests less invasive than colonoscopy for monitoring their child's IBD. Although providing explanation of their child's tests enhanced parents' understanding, it can also affect parents' levels of concern and comfort.

Purpose: To investigate the differences in the colon microbiota composition of Hirschsprung's disease (HSCR) patients with and without a history of postoperative Hirschsprung's associated enterocolitis (HAEC). Methods: Colon tissue microbiota was characterized by bacterial deoxyribonucleic acid (DNA) extraction and 16S rDNA sequencing for taxonomic classification and comparison. Results: The sequence diversity richness within samples was significantly higher in samples from patients with a history of postoperative HAEC. We observed an increased relative abundance of the phyla Bacteroidetes, Firmicutes and Cyanobacteria in HAEC patients and Fusobacteria, Actinobacteria and Proteobacteria in HSCR patients and, an increased relative abundance of the genera Dolosigranulum, Roseouria and Streptococcus in HAEC patients and Propionibacterium and Delftia in HSCR patients. Conclusion: Our findings provide evidence that the colon tissue microbiota composition is different in HSCR patients with and without postoperative HAEC.

Purpose: Digital communication is becoming increasingly important in clinical practice and research. The finding that stool consistency can be evaluated similarly using either "in vivo" or photographic material by health care professionals will decrease subjective interpretation by parents. The primary outcome of this study was the reliability of stool consistency scoring using the Brussels Infant and Toddler Stool Scale (BITSS) between fresh stools and their photos; the secondary outcome was the inter-rater reliability based on the fresh stools. Methods: Fresh stool samples from healthy children were collected in a day care center. These stools, and one month later the corresponding photos presented in a random order, were presented to 14 observers. Reliabilities were analyzed using absolute agreements and weighted and unweighted Cohen's κ. Results: In total, 202 samples were rated 576 times. Absolute agreement between photographic and real time assessment ranged between 71.1% and 83.3% among observers. This corresponded with substantial agreement (unweighted κ=0.70 [95% CI, 0.61-0.78]; weighted κ=0.86 [95% CI, 0.78-0.88]). The inter-observer agreement showed similar percentages of absolute agreement (81.4-82.0%) and κ-values corresponding with fair-to-moderate agreement. Conclusion: Our findings suggest that the assessment of fresh stool consistency can also reliably be done on photographic material when using the BITSS. This opens opportunities in scientific surroundings and in our daily life communication with parents and caretakers.

Purpose: We aimed to compare the prevalence rates and associated symptoms of constipation and fecal incontinence in children and young adults and evaluate how these patient groups cope with these disorders. Methods: A cross-sectional study was performed in which 212 children (8-17 years) and 149 young adults (18-29 years) from the general Dutch population completed a questionnaire about defecation disorders. Results: Constipation occurred in 15.6% of children and 22.8% of young adults (p=0.55), while the prevalence of fecal incontinence was comparable between groups (7%, p=0.91). The symptoms associated with constipation occurred as often in children as in young adults, while most fecal incontinence symptoms occurred more often in young adults. Approximately 43% of children had constipation for more than 5 years, while 26% of young adults experienced constipation since childhood. Only 27% of constipated children and 21% of constipated young adults received treatment (mostly laxatives). For fecal incontinence, 13% of children and 36% of young adults received treatment (mostly antidiarrheal medications or incontinence pads). Conclusion: In contrast to the general belief, the prevalence of defecation disorders and associated symptoms seem to be comparable in children and young adults. Only a few people with defecation disorders receive adequate treatment.

Purpose: Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver diseases in both adults and children with obesity. The aim of this study was to compare the changes in liver enzymes and metabolic profile in adolescents with fatty liver following selected school-based exercise (SBE) and high-intensity interval training (HIIT) interventions. Methods: In a semi-experimental study, 34 obese male adolescents with clinically defined NAFLD were divided into the HIIT (n=11, age=12.81±1.02 years, body mass index [BMI]=26.68±2.32 kg/㎡), selected SBE (n=11, age=13.39±0.95 years, BMI=26.47±1.74 kg/㎡), and control (n=12, age=13.14±1.49 years, BMI=26.45±2.21 kg/㎡) groups. The ultrasonography NAFLD grade, peak oxygen uptake (VO2peak), lipid profile, insulin resistance, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of the participants were measured before and after the exercise interventions. Results: The BMI, waist-to-hip ratio, and body fat percentage of the participants decreased, and a significant increase in VO2peak was observed after the intervention; however, the HIIT group showed a significant improvement compared with the SBE group (p<0.01). Significant reductions were observed in the levels of insulin resistance, triglyceride, total cholesterol, ALT, and AST in both groups, although high-density lipoprotein levels decreased only in the HIIT group (p<0.01). Further, a significant reduction in low-density lipoprotein level was observed in the training groups (p<0.01), but this decrease was not significant compared with the control group (p>0.01). Conclusion: HIIT and SBE are equally effective in improving health parameters in obese children and adolescents.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has influenced the lives of people worldwide. Little is known about the effects of the COVID-19 pandemic on the behavior and fears of pediatric patients with inflammatory bowel disease (IBD) and their families. We conducted a survey to determine the COVID-19 exposure, related perceptions, and information sources; medication compliance; and patients' and parents' behaviors, fears, and physician contact. Methods: An anonymous cross-sectional survey of pediatric patients with IBD and their parents at one pediatric gastroenterology unit of a university medical center was performed. Results: A total of 46 pediatric patients with IBD and 44 parents completed the survey. Parents of pediatric patients with IBD had high fear of their children becoming infected with severe acute respiratory syndrome coronavirus 2. They perceived schools as the most hazardous environment, whereas the children did not. Half the pediatric patients with IBD feared infection. Patients and parents felt sufficiently informed about COVID-19. The primary source of guidance for pediatric patients was their parents (43%), followed by television and social media, whereas the parents mainly consulted internet news websites (52.2%), television, and public health institutes. Pediatric patients with IBD adhered to their prescribed medication. They also showed cautious behavior by enhancing hand hygiene (84%) and leaving the house less frequently than before. However, in-person medical visits remained favored over video consultations. Conclusion: Although parents expressed overprotective concerns, both parents and pediatric patients with IBD are coping well with the COVID-19 pandemic. IBD-relevant information should be actively conveyed.

Purpose: Appendicitis is the most frequent urgency in pediatric age; the aim of this study was to investigate the association of quarantine for severe acute respiratory syndrome coronavirus 2 pandemic and the incidence of pediatric appendicitis in a specific macro area. Methods: We retrospectively analyzed the medical records of consecutive patients who underwent surgical exploration for acute appendicitis in the period March-April since 2014. This specific quarantine period was divided into two phases as indicated by National government. Patient data, demographics, characteristics and outcomes were studied and evaluated comparing patients treated during quarantine especially phase 1 vs. phase 2 (March-April 2020). Results: After reviewing medical charts following the inclusion and exclusion criteria, 155 patients were studied; focusing on the final outcome, it is possible to show a decreased amount of appendicitis during phase 1 and a progressive increase during phase 2; respect to previous years, there was a statistical increase in severity of appendicitis during quarantine (gangrenous vs. phlegmonous appendicitis). Conclusion: During this specific quarantine there was a reduction in appendicitis and a progressive increase during phase 2. These results offer new perspective among disease incidences during lockdown.

Purpose: A steady increase in Clostridioides difficile enteritis (CDE) has been reported recently. CDE is associated with intestinal dysbiosis, and vitamin D receptors are known to play an important role in this microbial imbalance as immunological regulators. We investigated the difference in vitamin D levels between children with CDE and those with other acute infectious enteritis. Methods: This retrospective study was conducted on children below 18 years of age who visited the Gil hospital, underwent investigation to assess vitamin D levels, and had confirmed gastrointestinal infection between January 2015 and December 2018. Patients were divided into two groups: the "CDE group" (n=18) and the "other infectious enteritis group" (n=88); their clinical characteristics, other laboratory results, and vitamin D levels were analyzed. Results: There was no difference in gender, age, and seasonal distributions between the CDE and other infectious enteritis groups. Other laboratory results were not significantly different between two groups, excluding serum albumin level (4.52±0.45 g/dL vs. 4.31±0.28 g/dL, p=0.011). The mean 25-hydroxy vitamin D level in the CDE group was higher than that in the control group (18.75±8.11 ng/mL vs. 14.50±6.79 ng/mL, p=0.021). Conclusion: Vitamin D levels in the CDE group were lower than normal but higher than the other infectious enteritis group. These results suggested that CDE has a different mechanism or susceptibility associated with vitamin D in children, and even marginal changes in vitamin D levels can act as a risk factor for infection.

Purpose: Nutrition screening is vital to ensure patients are appropriately managed in hospital. In paediatrics there is currently no universally accepted nutrition screening tool. The Nutrition Evaluation Screening Tool (NEST) was developed as an easy to use and practical screening tool for hospitalised children. We aim to evaluate compliance of the NEST and assess agreement of the NEST with the already validated nutrition screening tools, Screening Tool for Risk on Nutritional Status and Growth (STRONGkids), Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP) and the Subjective Global Nutritional Assessment (SGNA) tool. Methods: Retrospective review of 102 patient episodes at the Evelina London Children's Hospital. Electronic records were used to assess NEST compliance and to complete the nutrition tools for each patient episode. Cohen's kappa was used to determine the level of agreement between each nutrition tool. Results: There was moderate agreement between the NEST and the two screening tools, STRONGkids (κ=0.472) and STAMP (κ=0.416) for patients on initial screening at admission. 87.2% of patient episodes were NEST compliant within 24 hours of admission to hospital. Conclusion: The moderate agreement between these two already validated screening tools enhances the NEST's validity as a paediatric screening tool. The NEST had the strongest correlation with the SGNA tool compared to other screening tools. The NEST is user friendly screening tool for hospitalised children.

Purpose: Percutaneous endoscopic gastrostomy (PEG) tube placements are commonly performed pediatric endoscopic procedures. Because of underlying disease, these patients are at increased risk for airway-related complications. This study compares patient characteristics and complications following initial PEG insertion with general endotracheal anesthesia (GETA) vs. anesthesia-directed deep sedation with a natural airway (ADDS). Methods: All patients 6 months to 18 years undergoing initial PEG insertion within the endoscopy suite were considered for inclusion in this retrospective cohort study. Selection of GETA vs. ADDS was made by the anesthesia attending after discussion with the gastroenterologist. Results: This study included 168 patients (GETA n=38, ADDS n=130). Cohorts had similar characteristics with respect to sex, race, and weight. Compared to ADDS, GETA patients were younger (1.5 years vs. 2.9 years, p=0.04), had higher rates of severe American Society of Anesthesiologists (ASA) disease severity scores (ASA 4-5) (21% vs. 3%, p<0.001), and higher rates of cardiac comorbidities (39.5% vs. 18.5%, p=0.02). Significant associations were not observed between GETA/ADDS status and airway support, 30-day readmission, fever, or pain medication in unadjusted or adjusted models. GETA patients had significantly increased length of stay (eβ=1.55, 95% confidence interval [CI]=1.11-2.18) after adjusting for ASA class, room time, anesthesia time, fever, and cardiac diagnosis. GETA patients also had increased room time (eβ=1.20, 95% CI=1.08-1.33) and anesthesia time (eβ=1.50, 95% CI=1.30-1.74) in adjusted models. Conclusion: Study results indicate that younger and higher risk patients are more likely to undergo GETA. Children selected for GETA experienced longer room times, anesthesia times, and hospital length of stay.

Purpose: Ménétrier disease (MD) was first described in 1888, and 50 cases have been reported until now. We aimed to discuss the etiology, diagnostics, and management of MD in children. Methods: We searched for case reports published from 2014 till 2019 in English using PubMed. Articles were selected using subject headings and key words of interest to the topic. Interesting references of the included articles were also included. Results: The pathophysiology of MD is still uncertain. However, overexpression of transforming growth factor alpha with transformation of the gastric mucosa has been observed, which may be mediated by genetics and provoked by an infectious trigger. Clinically, MD is diagnosed by abdominal pain, vomiting, anorexia, and edema secondary to hypoalbuminemia. A gastroscopy with biopsy is the gold standard for the diagnosis of MD. In children, the disease is self-limiting and only requires supportive treatment. In general, children have a good prognosis and recover spontaneously within a few weeks. Conclusion: Few pediatric cases of MD have been described in recent years, and with all different etiology. Endoscopy with biopsy remains the golden standard for the diagnosis of MD, and in children, the disease is self-limiting.