Meal related symptoms in youth with chronic abdominal pain: Relationship to anxiety, depression, and sleep dysfunction.

OBJECTIVE: The objective of the current study was to describe meal-related symptoms in youth with chronic abdominal pain fulfilling criteria for a disorder of gut-brain interaction (DGBI) and their associations with anxiety, depression, and sleep disturbances. METHODS: This was a retrospective evaluation of 226 consecutive patients diagnosed with an abdominal pain-associated DGBI. As part of routine care, all had completed a standardized symptom history, the Sleep Disturbances Scale for Children (utilized to assess for disorders of initiation and maintenance of sleep and excessive daytime somnolence) and the Behavior Assessment System for Children-Third Edition (utilized to assess for anxiety and depression). Four meal related symptoms were assessed: early satiety, postprandial bloating, postprandial abdominal pain, and postprandial nausea. RESULTS: Overall, 87.6% of patients reported at least one meal related symptom and the majority reported at least three symptoms. All meal related symptoms were significantly related to each other. Postprandial pain and nausea were more often reported by females. Early satiety, postprandial bloating, and postprandial nausea, but not postprandial pain demonstrated significant though variable associations with anxiety, depression, disorders of initiation and maintenance of sleep, and disorders of excessive somnolence, but only in adolescents. CONCLUSIONS: Meal related symptoms are very common in youth with abdominal pain-associated DGBIs. Early satiety, bloating, and postprandial nausea demonstrate variable associations with anxiety, depression, and disordered sleep while increased postprandial pain was not associated with psychologic or sleep dysfunction, suggesting a different pathway for symptom generation.

Nonanaphylactic Variant of Alpha-Gal Syndrome as an Etiology for Chronic Gastrointestinal Symptoms in Children.

We report 3 pediatric patients who presented with only nonanaphylactic symptoms of alpha-gal syndrome. This report highlights the necessity of not discounting alpha-gal syndrome from a differential diagnosis for patients with recurrent gastrointestinal distress and emesis after consuming mammalian meat, even in the absence of an anaphylactic reaction.

High Rate of Emergency Department Care in Youth With Abdominal Pain-Associated Functional Gastrointestinal Disorders.

OBJECTIVES: The primary objective was to describe patterns of care delivery locations in youth with abdominal pain-associated functional gastrointestinal disorders (AP-FGID) and assess for differences in patterns of care delivery by sex and race. A secondary objective was to describe cost variability within the emergency department (ED). METHODS: Data were obtained using a large, single-vendor database that extracts and deidentifies data from the electronic health record across the outpatient, ED, and inpatient continuum of care. We evaluated patients 8 to 17 years of age seen over an 8-year period for a priority 1 diagnosis of an AP-FGID. Data collected included age, sex, race, encounter location, and total cost of ED encounters. We specifically assessed how often patients seen in the ED were also seen in outpatient or inpatient settings. RESULTS: A total of 53,750 patients (64% female; mean age, 13.3 ± 2.8 years) were identified and assessed. The most common location of care was the ED (48.8%) followed by the outpatient setting (46.2%). Of patients seen for a priority 1 AP-FGID diagnosis in the ED, only 3.7% were seen for a priority 1 diagnosis in the outpatient setting, and only 1% were seen in an inpatient setting. Overall, females received 42.5% of their care and males received 44.8% of their care in the ED. The overall rate of ED care was 66.9% for Hispanic, 61.5% for African American, 55.1% for Asian, 46.6% for Native American, and 36.9% for Caucasian patients. CONCLUSIONS: The ED is the most common location for care for youth with AP-FGIDs and, for the majority, seems to be the only location. This seems to be particularly true for Hispanic and African American patients. Given the often complex psychosocial needs of this patient group, processes need to be developed to transition these patients into the outpatient setting, ideally to programs specializing in chronic pain.

Individual Differences in the Relationship Between Pain Fear, Avoidance, and Pain Severity in a Chronic Abdominal Pain Sample and the Moderating Effect of Child Age.

BACKGROUND/PURPOSE: Most studies examining the components of the fear-avoidance model have examined processes at the group level. The current study used ecological momentary assessments to: (a) investigate the group and intraindividual relationships between pain fear, avoidance, and pain severity, (b) identify any heterogeneity between these relationships, and (c) explore the role of moderators to explain such heterogeneity. METHODS: Seventy-one pediatric patients with chronic abdominal pain (M = 13.34 years, standard deviation = 2.67 years) reported pain fear, avoidance, and pain severity four times per day over 14 days. RESULTS: Results indicated significant individual differences in the relationship between pain fear and pain avoidance predicting pain severity. Child age helped explain the heterogeneity in the relationships between pain avoidance and pain severity such that older children had a stronger and more positive relationship between these variables. The random effect between pain fear and pain severity also indicated a moderator trend of child age such that older children were likely to have a stronger and more positive relationship. CONCLUSIONS: The present study extends the fear-avoidance model by highlighting the importance of identifying potential individual differences when examining pain fear, avoidance, and pain severity. Furthermore, the current study suggests that child development should be considered in the model. However, future randomized control designs are necessary to explore the causal relationships between pain fear and avoidance on pain severity and potential developmental differences.

A cross-sectional study of nausea in functional abdominal pain: relation to mucosal mast cells and psychological functioning.

BACKGROUND: Nausea is a common symptom in youth with chronic abdominal pain. The aims of the current study were to assess: 1) the frequency of nausea in patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS), respectively, as defined by Rome IV criteria; and, 2) relationships between nausea and mucosal inflammation as defined by antral and duodenal eosinophil and mast cell densities. A secondary aim was to assess relationships between nausea and other gastrointestinal symptoms, non-gastrointestinal somatic symptoms, and psychological dysfunction. METHODS: Records from patients with pain associated functional gastrointestinal disorders were retrospectively reviewed for gastrointestinal and somatic symptoms and anxiety, depression, and somatizations scores as assessed by the Behavior Assessment System for Children (BASC-2). In addition, previous gastric and mucosal biopsies were assessed for mast cell and eosinophil densities, respectively. RESULTS: 250 patients, ages 8 to 17 years, were assessed. Nausea was reported by 78% and was equally prevalent in those with FD alone, those with IBS alone, and those with both FD and IBS. Nausea was associated with increased mean (21.4 vs. 17.5) and peak (26.2 vs. 22.9) duodenal mast cell densities as compared those without nausea. Nausea was also associated with a wide variety of individual gastrointestinal symptoms, as well as headaches, fatigue, and dizziness. Lastly, nausea was associated with elevated self-report scores for anxiety (55.2 vs. 50.0), depression (50.2 vs. 46.1), and somatization (70.3 vs. 61.8). CONCLUSIONS: Nausea is common in children and adolescents with pain-associated FGIDs as defined by Rome IV and is not unique to either FD or IBS. Nausea is associated with increased mucosal mast cell density, non-gastrointestinal somatic symptoms, and psychologic dysfunction.

The Association Between Affect and Sleep in Adolescents With and Without FGIDs.

OBJECTIVE: Adolescents with chronic pain associated with functional gastrointestinal disorders (FGIDs) experience negative impacts on their health behaviors (i.e., sleep) and are at risk for a range of problems related to negative affect, which may serve to exacerbate one another in a reciprocal fashion. This study aimed to determine if the strength of the relationship between affect and sleep differs across community adolescents and adolescents with FGIDs. It was hypothesized that shorter sleep durations would be associated with more negative affect and longer sleep durations would be associated with more positive affect, and that group membership would moderate these relationships. METHODS: Twenty-five adolescents with FGIDs were compared with 25 matched peers to examine the differential association between affect and total sleep time (TST). Models were estimated using SAS PROC MIXED for inter- and intraindividual differences. RESULTS: Models predicting TST revealed a significant three-way interaction among weekday, group status, and negative affect. Simple slopes indicated that when negative affect is one standard deviation below the child's own average on weekends, participants with FGIDs obtained significantly more sleep than those in the comparison group (ß = 47.67, p < .05). CONCLUSIONS: The findings of the present study show that when adolescents with FGIDs have lower negative affect on the weekend, when demands are likely reduced, they are able to obtain more TST. These findings confirm that unique relationships exist between negative affect and sleep duration for youth with FGIDs, and their interaction may hold value in understanding and addressing these targets.

Mucosal Th17 Cells Are Increased in Pediatric Functional Dyspepsia Associated with Chronic Gastritis.

BACKGROUND: Chronic gastritis is a common histologic finding in children with functional dyspepsia (FD). While Th17 cells have been implicated in other forms of gastritis, they have not been evaluated in chronic gastritis. AIMS: The aim of the current study was to assess Th17 cells in children with FD with and without chronic gastritis. METHODS: Densities were determined for Th17 cells, eosinophils, and mast cells, respectively, in both the gastric antrum and the duodenum. Densities were compared between five groups: FD with chronic gastritis (N = 20), FD without chronic gastritis (N = 20), Helicobacter pylori-associated gastritis (N = 10), Crohn's gastritis (N = 10), and normal controls (N = 10). Th17 densities were also compared between patients with and without early satiety. RESULTS: FD with chronic gastritis was associated with higher Th17 cell density as compared to normal controls and comparable to both H. pylori-associated gastritis and Crohn's gastritis. Eosinophil and mast cell densities were higher in FD patients with chronic gastritis as compared to either FD without gastritis or normal controls. Th17 density was higher in patients reporting early satiety but not in those with epigastric pain. CONCLUSIONS: FD with chronic gastritis is associated with higher Th17 cell, eosinophil, and mast cell density as compared to FD without chronic gastritis or normal controls. Chronic gastritis demonstrated Th17 cell density similar to that seen in other conditions where Th17 cells are believed to play a pathogenic role. Th17 cells may represent another therapeutic target in these patients.

Heart Rate Variability and Gastric Electrical Response to a Cold Pressor Task in Youth with Functional Dyspepsia.

BACKGROUND/AIMS: While stress has been implicated in functional dyspepsia (FD), the mechanisms by which stress results in symptoms are not well defined. The aim of the current study was to assess gastric myoelectric and autonomic changes in response to a physical stressor in youth with FD. METHODS: In a group of healthy controls and pediatric FD subjects, we recorded ECG and EGG signals 30 min before and 60 min after, a cold pressor task (CPT). Gastric EGG and heart rate variability (HRV) parameters were calculated in pre- and post-CPT stages and in short intervals. RESULTS: The pre-CPT percent tachygastria was higher in FD subjects as compared to controls. However, CPT did not induce any EGG changes in either controls or FD subjects and the two groups did not differ from each other post-CPT. The CPT resulted in an increase in HRV and standard deviation of NN intervals in controls; there was no change in any HRV parameter in FD subjects. CONCLUSIONS: Acute physical stress does not appear to induce gastric electrical abnormalities in youth with FD. Youth with FD appear to lack the normal flexible autonomic response to a physical stressor.

Novel Protective Role of Nicotinamide Phosphoribosyltransferase in Acetaminophen-Induced Acute Liver Injury in Mice.

Acetaminophen overdose is the most common cause of acute liver injury (ALI) or acute liver failure in the United States. Its pathogenetic mechanisms are incompletely understood. Additional studies are warranted to identify new genetic risk factors for more mechanistic insights and new therapeutic target discoveries. The objective of this study was to explore the role and mechanisms of nicotinamide phosphoribosyltransferase (NAMPT) in acetaminophen-induced ALI. C57BL/6 Nampt gene wild-type (Nampt+/+), heterozygous knockout (Nampt+/-), and overexpression (NamptOE) mice were treated with overdose of acetaminophen, followed by histologic, biochemical, and transcriptomic evaluation of liver injury. The mechanism of Nampt in acetaminophen-induced hepatocytic toxicity was also explored in cultured primary hepatocytes. Three lines of evidence have convergently demonstrated that acetaminophen overdose triggers the most severe oxidative stress and necrosis, and the highest expression of key necrosis driving genes in Nampt+/- mice, whereas the effects in NamptOE mice were least severe relative to Nampt+/+ mice. Treatment of P7C3-A20, a small chemical molecule up-regulator of Nampt, ameliorated acetaminophen-induced mouse ALI over the reagent control. These findings support the fact that NAMPT protects against acetaminophen-induced ALI.

A comparison of the diagnosis of gastroparesis in 4 h pediatric gastric emptying studies versus 2 h studies.

BACKGROUND: In adults, there is a consensus for standards to diagnose gastroparesis utilizing a gastric emptying study as the key diagnostic modality but there is no consensus for a standard in pediatrics. Additionally, some cost savings might be achieved if symptoms could be utilized to predict patients with gastroparesis. The aims of the current study were to confirm the sensitivity of a 4 h study in the pediatric population and to assess whether the severity of symptoms were predictive of delayed gastric emptying. STUDY: This was a single site, two part study. In the first part, results were reviewed for all patients who had completed a 4-h, solid gastric emptying study over the course of a 3 year period. In the second portion of the study, participants scheduled for a gastric emptying study, completed a modified GCSI questionnaire. RESULTS: Out of a total of 109 participants, at 2 h, 14 participants (12.8%) had abnormal studies as compared to 26 (23.85%) participants who had abnormal studies at 4 h (p = .0027). Of the 95 participants with normal studies at 2 h, 15% (14/95) were abnormal at 4 h. There were no differences in symptom severity scores between those with slow and those with normal emptying at either 2 h or 4 h. CONCLUSIONS: Our study adds independent confirmation that extending studies from 2 to 4 h increases the diagnostic yield and should be the standard in children and adolescents as it is in adults.

Classification of pediatric functional gastrointestinal disorders related to abdominal pain using Rome III vs. Rome IV criterions.

BACKGROUND: The primary purpose of this study was to compare Rome III and IV evaluation criteria for irritable bowel syndrome (IBS), functional dyspepsia (FD), and an overlap syndrome consisting of both IBS and FD by assessing the frequency of each diagnosis in a population of children with chronic abdominal pain. Frequencies of Rome IV FD subtypes of postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) were determined and FD/IBS overlap symptom associations were also assessed. METHODS: We conducted a cross-sectional retrospective chart review of 106 pediatric patients who had completed standardized medical histories as part of their evaluation for chronic abdominal pain. The patients ranged from eight to 17 years of age and reported having abdominal pain at least weekly for 8 weeks. Patients whose evaluation revealed gastrointestinal disease were excluded. The patients' diagnoses were determined by a single pediatric gastroenterologist utilizing the specific criteria for Rome III and IV, respectively. RESULTS: Patients were significantly more likely to be diagnosed with FD (84.9% vs. 52.8%), IBS (69.8% vs. 34%), and FD/IBS overlap (58.5% vs. 17.9%) by Rome IV criteria, as compared to Rome III criteria. With regard to Rome IV FD subtypes, 81.1% fulfilled criteria for PDS, 11.1% fulfilled criteria for EPS, 6.7% fulfilled criteria for both, and 1.1% did not fulfill criteria for either. Finally, we found an increased frequency of diarrhea and pain with eating in the overlap group compared to the non-overlap group of Rome III, while only an increased frequency of diarrhea was found in the overlap group compared to the non-overlap group of Rome IV. CONCLUSIONS: Our data demonstrate that utilizing Rome IV criteria, as compared to Rome III, results in an increase in the diagnosis of FD, a two-fold increase in the diagnosis of IBS, and a three-fold increase in the diagnosis of FD/IBS overlap. Rome IV criteria appears to result in greater heterogeneity within diagnostic categories. It is important to determine whether Rome IV diagnoses are predictive of treatment response, and if so, whether assessing symptom variability within a diagnosis will enhance the ability to select patients for a particular treatment.

Is histologic esophagitis associated with dental erosion: a cross-sectional observational study?

BACKGROUND: Gastroesophageal reflux disease (GERD) affects 15-25% of children and adolescents in the United States. The diagnosis of GERD in children is complex as reported symptoms or symptom profiles have been found to be unreliable. Frequently, the diagnosis must be confirmed by objective tests such as pH monitoring or histological evidence of esophagitis on an esophageal biopsy. Dental erosion has been shown to be associated with GERD as an atypical complication and has the potential to be a marker of GERD. The purposes of this study were to compare the frequency and patterns of dental erosion in children and adolescents with and without histologic esophagitis. METHODS: Twenty-five subjects were recruited from patients scheduled for an upper gastrointestinal endoscopy. Information regarding potential GERD symptoms, food habits, and dental hygiene habits were obtained. Intra-oral photographs were taken, and a dental exam for erosion was performed. The results of a standard biopsy taken from the lower third of the esophagus during an endoscopy were used to divide subjects into either the control group or the GERD group (i.e. those with histologic esophagitis). RESULTS: Twenty-two subjects yielded 586 evaluable teeth. No significant difference was found between frequency or erosion patterns of those with and without histologic esophagitis. Dental erosions were more frequent in primary teeth. CONCLUSIONS: Dental erosions do not appear to be associated with histologic esophagitis indicative of GERD.

Decreased Pregnane X Receptor Expression in Children with Active Crohn's Disease.

Expression of the pregnane X receptor (PXR) has been reported to be decreased in animal models of inflammatory bowel disease (IBD). To investigate the differential expression of PXR in children with Crohn's disease, a type of IBD, RNA was extracted from archived intestinal biopsies from 18 children with Crohn's disease (CD) and 12 age- and sex-matched controls (aged 7-17yrs). The aim of this investigation was to compare the relative mRNA expression of PXR, cytochrome p450 3A4 (CYP3A4), and villin 1 (VIL1) (a marker of epithelial cell integrity) in the inflamed terminal ileum (TI) versus noninflamed duodenum of children with CD. Relative expression was determined via reverse transcription real-time quantitative polymerase chain reaction, data normalized to glyceraldehyde 3-phosphate dehydrogenase, and differences in gene expression explored via paired t tests. PXR expression was decreased in the inflamed TI versus noninflamed duodenum (TI = 1.88 ± 0.89 versus duodenum = 2.5 ± 0.67; P < 0.001) in CD, but not controls (TI = 2.11 ± 0.41 versus duodenum = 2.26 ± 0.61; P = 0.52). CYP3A4 expression was decreased in CD (TI = -0.89 ± 3.11 versus duodenum = 1.90 ± 2.29; P < 0.05), but not controls (TI = 2.46 ± 0.51 versus duodenum = 2.60 ± 0.60; P = 0.61), as was VIL1 (CD TI = 3.80 ± 0.94 versus duodenum = 4.61 ± 0.52; P < 0.001; controls TI = 4.30 ± 0.35 versus duodenum = 4.47 ± 0.40; P = 0.29). PXR expression correlated with VIL1 (r = 0.78, P = 0.01) and CYP3A4 (r = 0.52, P = 0.01) expression. In conclusion, PXR, CYP3A4, and VIL1 expression was decreased only in the actively inflamed small intestinal tissue in children with CD. Our findings suggest that inflammation has the potential to influence expression of genes, and potentially intestinal proteins, important to drug disposition and response. The observed differential patterns of gene expression support further investigation of the role of PXR in the pathogenesis and/or treatment of pediatric Crohn's disease.

Prevalence of overlap syndromes and symptoms in pediatric functional dyspepsia.

BACKGROUND: The purpose was to evaluate the overlap frequency of irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and overactive bladder syndrome (OBS), as well as other gastrointestinal and systemic symptoms, in functional dyspepsia (FD). Additionally, we sought to determine whether adult Rome III FD subtypes were uniquely related to overlap syndromes or symptoms. METHODS: The study was a retrospective review of 100 consecutive pediatric patients, age 8-17 years, diagnosed with FD. All had completed a standardized medical history including gastrointestinal and systemic symptoms as well as specific symptoms related to GERD and OBS. The frequency of overlap with IBS, GERD, and OBS were determined for the whole group and for those fulfilling adult FD subtype criteria. Individual symptoms were also compared by FD subtype. RESULTS: Overlap IBS was present in 33 % of the FD patients. At least one GERD symptom was present in 74 % of patients with 41 % reporting heartburn. At least one OBS symptom was present in 44 % of patients with 29 % reporting urinary urgency. Other than pain, the most common reported gastrointestinal symptom was nausea (86 %). Systemic symptoms were common. Overlap syndromes/symptoms did not vary by FD subtype. Postprandial distress syndrome was associated with pain with eating, weight loss, and waking at night to have a stool. CONCLUSIONS: FD is a heterogeneous condition in children and adolescents with significant variability in the presence of gastrointestinal and non-gastrointestinal symptoms and overlap syndromes. Varying symptom profiles need to be accounted for and analyzed in studies involving subjects with FD.

Investigation of potential early Histologic markers of pediatric inflammatory bowel disease.

BACKGROUND: Early manifestations of pediatric inflammatory bowel disease (IBD) can be relatively nonspecific. Initial mucosal biopsies may not be conclusive, delaying the diagnosis until subsequent biopsies demonstrate typical histologic features of IBD. We hypothesized that certain inflammatory cell types may be utilized as early histologic indicators of IBD in children. METHODS: A retrospective analysis compared histologic findings from initially inconclusive or negative endoscopic studies in 22 patients who were subsequently diagnosed with IBD (after diagnostic endoscopy) to those of 20 comparison patients with functional abdominal pain matched for age, gender, and study type. A pediatric pathologist, blinded to study group, reviewed biopsies for histologic abnormalities. Eosinophil densities were obtained from the stomach, duodenum, and rectosigmoid areas. Immunohistochemistry (IHC) staining for tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-9 (MMP-9) was performed on the stomach and rectosigmoid areas. RESULTS: Gastritis and colonic crypt distortion were present in the IBD group at a greater rate (61 % vs. 22 %, p = 0.020; 34 % vs. 4 %, p = 0.008, respectively). Peak and mean eosinophil densities in the rectosigmoid area were greater in the IBD group (17.0/hpf vs. 5.0/hpf, p = 0.0063; 12.3/hpf vs. 4.2/hpf, p = 0.0106, respectively). TNF-α and MMP-9 staining did not reveal any significant differences. CONCLUSIONS: Our data suggests that significantly greater inflammation in the stomach, crypt distortion in the colon, and eosinophilia in the rectosigmoid distinguished the IBD group from the comparison group at the time of the initial endoscopic evaluation.

A Pilot Study of Ketotifen in Patients Aged 8-17 Years with Functional Dyspepsia Associated with Mucosal Eosinophilia.

BACKGROUND AND OBJECTIVE: Mast cells have been implicated in abdominal pain-associated disorders of gut-brain interaction, such as functional dyspepsia. As such, ketotifen, a second-generation antihistamine and mast cell stabilizer, could represent a viable treatment option in these conditions. The primary aim of the current pilot study was to assess clinical response to ketotifen and assess pharmacokinetics in youth with functional dyspepsia. METHODS: We conducted a pilot randomized, double-blind, placebo-controlled, cross-over trial of ketotifen in 11 youth with functional dyspepsia and duodenal mucosal eosinophilia with 4 weeks of active treatment at a dose of 1 mg twice daily. Global clinical response was graded on a 5-point Likert Scale. A single plasma sample was obtained at steady state for pharmacokinetic analysis. RESULTS: Ketotifen was not superior to placebo with regard to global clinical response. Only 18% of patients demonstrated a complete or near-complete clinical response. The estimated half-life was 3.3 h. CONCLUSIONS: While ketotifen was not superior to placebo, this study highlights several important challenges for developing drug trials for youth with chronic abdominal pain. Recommendations are made for designing a larger treatment trial for ketotifen in this patient group. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov: NCT02484248.

Anti-TNF, infliximab, and adalimumab can be effective in eosinophilic bowel disease.

BACKGROUND: Eosinophilic enterocolitis (EEC) is an emerging distinct inflammatory bowel disease of unknown etiology. There are no published data on the effect of infliximab (IFX) or adalimumab (ADA) for the treatment of refractory cases. METHODS: A report of all pediatric cases with EEC treated with anti-tumor necrosis factor, identified after an open international call. RESULTS: We describe here the first 8 children with refractory EEC who were treated with IFX (75% boys; mean age at diagnosis 8.6 ± 4.03 [range 1.6-14 years]; mean age at IFX treatment 11.7 ± 4.4 [range 4.2-16 years]). Allergic and infectious causes of EEC were excluded in all cases. Rapid and complete clinical remission was documented in 6 (75%) children following the induction infusions: 3 (38%) with endoscopic remission, 2 (25%) with endoscopic improvement, and 1 unknown. Four of the 6 responders had secondary loss of response and were switched to ADA, 3 of whom with sustained remission using high doses. Overall, the 6 responders were followed for a median of 7 years (range 4-12; interquartile range 6.4-8.8 years) without evidence of developing Crohn disease or ulcerative colitis. The only case with macroscopic findings on endoscopy was a primary nonresponder. CONCLUSIONS: IFX and ADA may be effective in cases of refractory idiopathic EEC; however, because this is an uncontrolled report, further prospective studies are warranted.

Parental illness encouragement behavior among children with functional gastrointestinal disorders: a factor analysis with implications for research and clinical practice.

The objective of the current study was to assess the factor structure of the Illness Behavior Encouragement Scale (IBES) by Walker and Zeman (1992) among children with functional gastrointestinal disorders (FGIDs). Two hundred seventy nine children (63 % female), and 135 primary caregivers (90.8 % mothers), recruited from a large Midwestern children's hospital completed the IBES, a 12-item measure of parental behavior in response to abdominal pain episodes. Findings suggested the IBES possesses two conceptually distinct scales that are invariant across parent self- and child-report, and are consistent with previous factor analysis in a Dutch sample of children with headaches. Different types of parental behaviors exist that naturally cluster and diverge in reliable ways. Future research is warranted to determine if these different types of parental behavior may differentially influence illness outcomes among children with FGIDs.

Diagnostic role of fractional exhaled nitric oxide in pediatric eosinophilic esophagitis, relationship with gastric and duodenal eosinophils.

BACKGROUND: Eosinophilic esophagitis (EoE) is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies. A non-invasive and cost-effective alternative for management of EoE is being researched. Previous studies assessing utility of fractional exhaled nitric oxide (FeNO) in EoE were low powered. None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO. AIM: To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity. METHODS: Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study. Patients on steroids and with persistent asthma requiring daily controller medication were excluded. FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer (NIOX MINO, Aerocrine, Inc.; Stockholm, Sweden) prior to endoscopy. Based on the esophageal peak eosinophil count (PEC)/high power field on biopsy, patients were classified as EoE (PEC ≥ 15) or control (PEC ≤ 14). Mean FeNO levels were correlated with presence or absence of EoE, eosinophil counts on esophageal biopsy, and abnormal downstream eosinophilia in the stomach (PEC ≥ 10) and duodenum (PEC ≥ 20). Wilcoxon rank-sum test, Spearman correlation, and logistic regression were used for analysis. P value < 0.05 was considered significant. RESULTS: We recruited a total of 134 patients, of which 45 were diagnosed with EoE by histopathology. The median interquartile range FeNO level was 17 parts per billion (11-37, range: 7-81) in the EoE group and 12 parts per billion (8-19, range: 5-71) in the control group. After adjusting for atopic diseases, EoE patients had significantly higher FeNO levels as compared to patients without EoE (Z = 3.33, P < 0.001). A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels (r = 0.30, P < 0.005). On subgroup analysis within the EoE cohort, higher FeNO levels were noted in patients with abnormal gastric (n = 23, 18 vs 15) and duodenal eosinophilia (n = 28, 21 vs 14); however, the difference was not statistically significant. CONCLUSION: After ruling out atopy as possible confounder, we found significantly higher FeNO levels in the EoE cohort than in the control group.

Overactive bladder syndrome symptoms in youth with abdominal pain-associated disorders of gut-brain interaction.

The purpose of the current study was to assess the frequency of overactive bladder syndrome (OBS) symptoms and their relationship to gastrointestinal symptoms in youth with abdominal pain-associated disorders of gut-brain interaction (AP-DGBI). This is a retrospective study of 226 youth diagnosed with an AP-DGBI. As part of standard care, all patients completed a symptom questionnaire regarding gastrointestinal and non-gastrointestinal symptoms including increased urinary frequency, nighttime urination, and urinary urgency. Overall, 54% of patients reported at least one OBS symptom. Increased frequency of urination was reported by 19%, urinary urgency by 34%, and nighttime urination by 36%. Increased frequency of urination and urinary urgency were associated with a change in stool form, a change in stool frequency, and in those fulfilling criteria for IBS. Increased frequency of urination was reported more frequently in those reporting predominantly loose stools (33% vs. 12%). Urinary symptoms are common in youth with AP-DGBI. Increased urinary frequency and urinary urgency are specifically associated with IBS, with increased urinary frequency being primarily associated with diarrhea predominant IBS. Further studies are needed to determine the impact of OBS on AP-DGBI severity and quality of life, and whether they impact DGBI treatment.