USE OF FULL THICKNESS BIOPSIES IN PEDIATRIC PATIENTS WITH SEVERE GASTROPARESIS SYMPTOMS IN COMPARISON TO ADULT PATIENTS

Background: The low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet, which restricts FODMAP intake, currently is used as a treatment for pain-related disorders of gut-brain interaction (DGBI). A FODMAP Gentle diet, which is less restrictive, has been proposed as a pediatric-friendly alternative to a complete low FODMAP diet (PMID: 36297053).
Objectives: In a clinical sample of children with DGBI from the US to: 1) Characterize the high FODMAP foods consumed; and 2) Determine the degree to which a FODMAP Gentle diet would restrict commonly consumed high FODMAP foods
Methods: Children ages 7-13 years with DGBI enrolled in an ongoing randomized controlled trial based in the US completed 3-day baseline food records. High FODMAP foods in the participants’ diets were identified. The foods were characterized further by the food groups/categories to which the FODMAPs belonged. Whether the FODMAP Gentle diet would restrict the consumed food also was determined.
Results: Eighty-six participants (53, 61.6% female) with a median (IQR) age of 10.5 (9.1-12) years were studied. A total of 1609 high FODMAP foods were consumed by the participants and each participant consumed a median (IQR) of 6 (4.7-7.9) high FODMAP foods per day. High FODMAP foods containing fructans were most prevalent in the diet, followed by those containing lactose and fructose (Table 1). Wheat-based high FODMAP foods were the most prevalent food category consumed, followed by dairy, fruits/fruit juices, beverages, and condiments (Table 1). 1078 (67%) of the high FODMAP foods consumed were ultra-processed and 274 (17%) contained high fructose corn syrup as a major ingredient. High FODMAP foods were categorized into 79 food categories with milk, breaded animal protein, and sodas being the most frequently consumed (Table 2). 1,302 (81%) of consumed high FODMAP foods would be restricted on a FODMAP Gentle diet.
Conclusion: Children with DGBI in the US frequently consume high FODMAP foods. The most consumed FODMAPs are fructans followed by lactose and fructose related to the intake of wheat-based foods, dairy, fruits/fruit juices, and beverages. The vast majority of high FODMAP foods commonly consumed would be restricted on a FODMAP Gentle diet.

Background: The use of electronic health records (EHRs) has received attention as a method to conduct novel outcome research and generate real-world evidence at lower cost than traditional clinical trials. Aim: Evaluate utility of routinely collected EHR data from a Patient-Centered-Outcome-Research-Network (PCORnet) network to identify clinical, demographic, and lab characteristics that are associated with increased risk of treatment escalation (TE) in children newly diagnosed with UC. Methods: Multicenter deidentified EHR data (01/2010 – 12/2021) were collected from the Greater Plain Collaborative (GPC) of13 healthcare systems in the Midwest. Eligible pediatric population with UC was selected using ICD codes for UC excluding chronic proctitis. Standard treatment regimens of mesalamine or oral/IV corticosteroids, use of biologics and/or immunomodulators (IM), as well as colectomy (COL) were identified using RXNORM and CPT codes. Missing information on initial therapy was exclusionary. TE defined as a composite endpoint of receiving biologics and/or IM and/or COL after initial standard treatment. Demographic characteristics were compared against the prospective pediatric UC cohort from the PROTECT Study (NCT01536535). Relevant clinical (height, weight, BMI, hospitalization) and lab (hemoglobin, serum albumin, erythrocyte sedimentation rate, C-reactive-protein, platelet count, total white blood cell count and differential) characteristics at baseline were extracted based on domain knowledge using ICD and LOINC codes. Odds ratios of univariate and multivariable logistic regression and hazard ratios of univariate and multivariable cox proportional survival models were applied to identify potential discriminative characteristics associating with TE and time to TE, respectively. Missing lab values were imputed using multivariate imputation by chained equation. Results: 509 eligible pediatric UC patients (4-17 yrs) started with standard treatment were identified and compared to the PROTECT cohort (Table 1) being comparable except for lower rate of hospitalization at baseline. 219/509(42%) had TE at median[P25, P75] days of 95[14,338] since initial treatment, 20/509 (4%) underwent COL at median[P25,P75] days of 85[9,255]. The final logistic regression and cox survival model both showed moderate discriminative power to predict TE. The common positive predictors for TE and time-to-TE were high monocyte proportion and platelet counts. Race of Black/African American, BMI z-score, hemoglobin level, lymphocyte proportion, albumin were negatively associated with TE and time-to-TE (Table 2). Conclusion: This study demonstrates that multicenter EHR data can be used to identify a trial-comparable study sample of potentially larger size and to identify clinically meaningful endpoints for conducting outcome analysis and generating real-world evidence.

Background: Helicobacter pylori (H. pylori) antimicrobial resistance continues to increase globally with negative impact on eradication rates. Limited data is available in pediatric population in the United States with most studies reporting on resistance rates from Europe, Asia and isolated reports from Latin America. We collected epidemiological data to characterize the trends of H. pylori antimicrobial resistance in a United States pediatric population.

Methods: Retrospective cohort study from two pediatric tertiary care centers (01/2015 to 10/2022). Patients were included if they had histological evidence of H. pylori in gastric biopsies and data on antimicrobial resistance either by gastric biopsy culture via agar dilution and/or molecular testing in formalin fixed paraffin embedded gastric biopsies. Demographic variables, ZIP code, date of upper endoscopy, and endoscopic findings were extracted from the electronic medical records of the two hospitals. To enable analysis of socioeconomically-related health disparities, each ZIP code was assigned a socioeconomic status (SES) ranking with 1 being the lowest SES and 5 the highest.

Results: Two hundred and sixty-five patients (265) were included; mean age 12.29 ± 4.5 SD, 46% Male, 47% Caucasian, 35% Hispanic. Endoscopic findings: gastritis (94.7%), duodenitis (21.8%), gastric ulcer or erosion (3%), duodenal ulcer or erosion (8%), other findings (esophagitis) (5.7%). One hundred and fourteen (43%) of patients were resistant to at least one antimicrobial. Resistance to antimicrobials was as follows: clarithromycin (23.8%), metronidazole (21.5%), fluoroquinolones (9%), rifabutin (3.4%), amoxicillin (2.3%) and tetracycline (<1%). Twenty-one patients (8%) were resistant to two antimicrobials, 8 (3%) to three antimicrobials and 3 (1%) to four. Logistic regression models were used to assess associations between demographic and clinical features and the presence of antimicrobial resistance to any antimicrobial. In univariate analysis, three variables: low SES, Asian race, and having endoscopic finding of esophagitis were significant. In the final model, low SES and Asian race were significantly associated with antibiotic resistance.

Conclusion: H. pylori antimicrobial resistance to clarithromycin and metronidazole is above the 15% threshold recommended for choosing alternative empiric regimens. Race and low SES are associated with presence of antimicrobial resistance to any antimicrobial.

Objectives
To increase the safety of endoscopy in the era of the COVID-19 pandemic, we described a negative airflow box with a leak-proof system.
Methods
A transparent box was connected to a High Efficiency Particulate Air (HEPA) filter to create the negative pressure room and was placed over the patient’s head and shoulders. A rubber glove was fastened to the endoscopic port to avoid aerosol leakage. For a 90-second interval, incense sticks were used to create fine particulate matter (PM), which was intended to resemble virus particles. The front and right sides and inside of the box were chosen as the locations for the PM 2.5 sensors. As control and test circumstances, respectively, the effectiveness of the negative pressure and leak-proof systems was qualified with and without negative pressure.
Results
In control conditions, PM 2.5 gradually grew at the front side (493.2 + 208.9 mcg/m³), moved to the right side (185.1 + 118.4 mcg/m³), and then within the box (296.9 + 266.6 mcg/m³), reaching a stable state at the front side by 600 mcg/m³ in 11 seconds. While in test condition, PM 2.5 was rapidly moved to the inside (544.7+164.1 mcg/m³; p < 0.001) and reached a steady state in 10 seconds, with only a small number of particles detected outside (22.1+1.4 mcg/m³; p < 0.001 and 18.3+0.7 mcg/m³; p < 0.001 at the front and right side, respectively).
Conclusions
The negative pressure and glove leak proof had an efficacy to reduce aerosol transmission.

Background Meal-related symptoms were shown to be common in the general adult population and more frequent in those with disorders of gut-brain interaction (DGBIs) and those with more psychologic distress. We have previously shown PDS to be associated with psychologic dysfunction in youth with FD. To our knowledge, there have not been any previous pediatric studies assessing meal-related symptoms more broadly with psychologic impairment. The purpose of the current study was to describe meal-related symptom frequencies across a referral population of children with AP-DGBI including both FD and IBS and to assess associations with anxiety, depression, and sleep dysfunction.
Methods This was a retrospective study assessing 226 consecutive patients diagnosed with an AP-DGBI by a single board-certified pediatric gastroenterologist. As part of routine care, all patients completed a broad gastrointestinal symptom questionnaire which included all symptoms utilized in Rome IV criteria. Meal-related symptoms analyzed included early satiety, postprandial bloating, increased pain with eating, and increased nausea with eating. Also, as part of routine care, parents completed The Sleep Disturbances Scale for Children (SDSC) The questionnaire assesses various problems related to sleep in school-aged children and adolescents. The SDSC provides sub-scales, two of which were analyzed in the current study including: 1) disorders of initiating and maintaining sleep (DIMS); 2) disorders of excessive somnolence (DOES). Also, as part of routine clinical care, patients completed the Behavior Assessment System for Children – Third Edition (BASC-3). Standardized T scores for the self-report depression and anxiety were used for analysis in the current study
Results Overall, 87.6% of patients reported at least one meal related symptom. A single meal related symptom was reported by 11.1%, two symptoms by 24.3%, three symptoms by 24.8%, and all four symptoms by 27.4%. All four symptoms were significantly related to each other. Increased nausea with eating, early satiety, and postprandial bloating, respectively, were associated with higher scores for both anxiety and depression. Increased nausea with eating was associated with higher scores for DIMS and early satiety and postprandial bloating, respectively, were associated with higher scores for DOES. Increase pain with eating had no significant associations to anxiety, depression, or sleep disturbances.
Conclusions Meal-related symptoms are very common in youth with DGBIs and have significant yet variable relationships to psychologic dysfunction and sleep disturbances. The presence of meal-related symptoms should prompt further evaluation for anxiety, depression, and sleep disturbances.

Introduction: There is a bidirectional relationship between sleep and pain disturbances. Sleep disturbances increases the risk for pain, particularly among children with chronic diseases. The presence of chronic pain can also interfere sleep. There is a lack of published literature on the impact of sleep disturbances in adolescents with Abdominal Pain Predominant Disorders of Gut-Brain Interaction (AP-DGBIs). Hence, we aimed to determine the subjective sleep characteristics of children diagnosed with AP-DGBIs compared to healthy peers and hypothesized that children with AP-DGBIs will have higher sleep disturbances compared to healthy children.

Methods: This study included children ages 11 to 18 years from a large urban public school. Children with diagnosis of a sleep or organic gastrointestinal disorder were excluded. All participants filled out demographic data, baseline sleep history, and validated questionnaires: the Rome 4 diagnostic questionnaire (QPGS), [Adolescent Sleep Wake Scale-short form (ASWS), Pediatric Insomnia Severity Index (PISI), Epworth Sleepiness Scale for Children (ESS), Patient-Reported Outcomes Measurement Information System (PROMIS) Ped SF v1.0 - Sleep Disturbance 8a (SD) and Sleep-Related Impairment 8a (SRI)]. Parents filled the Sleep Hygiene Inventory for Pediatrics (SHIP). Cases (AP-DGBIs) were matched 1:1 with controls based on age and gender.

Results: We included 120 participants (60 cases and 60 controls). Mean age was 13.9 ± 1.9y in both groups. Children with AP-DGBIs had worse sleep quality. Children with AP-DGBIs were more likely to require more than 30 minutes to fall asleep (p=0.047), had worse daytime sleepiness (p=0.002), endorsed more gasping/choking/snorting (p=0.031) and nightmares (p=0.013) during sleep than healthy peers. There was no difference between total hours of sleep, rates of snoring, respiratory pauses, tonsillectomy, sleepwalking and restless legs between the two groups. Similarly, except for higher stress levels for cases (p=0.012), the groups did not differ based on their caffeine consumption prior to sleep, time between dinner and sleep or differences in activities before going to sleep. Children with AP-DGBIs had lower ASWS scores (p=0.0000) suggesting poor sleep quality, higher insomnia severity (p=0.0009), sleep disturbance (p=0.0000), sleep related impairment (p=0.0001), daytime sleepiness (p=0.002) and sleep hygiene scores (p=0.014, table 1).

Conclusions: Children with AP-DGBIs have worse sleep quality, insomnia, daytime sleepiness, sleep disturbance and sleep related impairment compared with healthy peers. Future studies are needed to further correlate these with GI symptoms and disability and identify possible mechanisms by which sleep disturbances affect GI symptoms and vice versa.

Introduction: Utility of bioelectric devices and other surgical procedures in children with the symptoms of severe upper gastrointestinal motility disorders have led to the intentional acquisition of full thickness gastric biopsies (FTBx). There is a paucity of data about these tissues and there is more literature analyzing adult patient samples. We report histologic analysis of full thickness gastric biopsies from a large cohort of pediatric patients with gastroparesis syndrome (GpS). We compare this cohort with an adult cohort with similar symptomatology as part of an ongoing data base.
Method: 20 pediatric patients (range 1 to 17 years old) and 225 adult patients with severe gastroparesis underwent full thickness gastric biopsy from the gastric antral/body area at the University of Louisville and Norton Children’s Hospital at the time of placement of gastric electrical stimulator, feeding tube and/or pyloroplasty surgery. Samples were analyzed for trichrome stain (fibrosis), mast cell tryptase and CD 117 (Interstitial cells of Cajal), S-100 (neural fiber cells), CD68 (inflammation) and for CD3, CD4, CD8, CD20 cells from both inner and outer layers of the muscularis propria. Standardized FDA compliant patient reported outcomes symptom scores (Trad-PRO), health related quality of life (HRQOL) via DRG based Investigator derived Outcome Measure Scores (IDIOMS), and gastric emptying study results at baseline and at one year follow up after gastric stimulator placement or related procedures were compared between two groups. Results were reported as median [IQR] and compared by non-parametric tests, using R statistical software.
Results: Pediatric patients reported less severe abdominal pain and bloating, and lower Trad-Pro scores compared to adult patients at baseline, but had similar reports of nausea, vomiting, and anorexia. IDIOM scores were equivalent between groups. Both adult and pediatric patients reported improved symptoms at one year compared to baseline. Pediatric patients’ biopsy samples had less CD68 cells of the inner layer of the muscularis propria (p<0.001), less S-100 staining of the outer layer (p=0.01) and less CD8 staining of the inner (p=0.013) layer. CD3, CD4, and mast cell tryptase levels were also lower in pediatric patients than adult controls but these results did not achieve statistical significance. Fibrosis was common in adult patients and was rarely seen in pediatric patient samples.
Conclusion: Pediatric patients with severe gastroparesis syndromes have full thickness gastric biopsy abnormalities that are similar, but not identical to, adult patients. These findings indicate the need for wider use of tissue analysis in severely symptomatic pediatric patients.