One-Year Outcomes Among Children Identified With Celiac Disease Through a Mass Screening Program.

BACKGROUND & AIMS: Celiac disease (CD) mass screening remains controversial in part because of a paucity of data to support its benefit. The Autoimmunity Screening for Kids study is a mass screening study for pediatric CD and type 1 diabetes in Colorado. METHODS: This study prospectively follows up children ages 1 to 17 years who screened positive for tissue transglutaminase IgA autoantibodies in the Autoimmunity Screening for Kids study subsequently referred for diagnostic evaluation. Children diagnosed with CD by biopsy or serologic criteria were included in this study. Evaluation at baseline and 12 month follow-up evaluation included demographics, laboratory studies, symptoms, health-related quality of life, anxiety/depression, and gluten-free diet adherence. Paired Student t test, chi-square, and Wilcoxon sign rank tests compared baseline and follow-up data. For symptom scores, odds of improvement were assessed. RESULTS: Of the 52 children with CD enrolled, 42 children completed 12-month follow-up evaluation. On the symptom questionnaire completed at diagnostic evaluation, 38 of 42 children reported 1 or more symptoms. CD mean symptom severity and frequency scores improved from baseline to follow-up evaluation (P < .001). Reported health-related quality of life scores improved among caregivers (P = .002). There was no significant change in reported anxiety or depression. Iron deficiency without anemia was common at baseline (21 of 24 children; 87.5%) and normalized at follow-up evaluation (11 of 21 children; 52.3%). Twenty-six of 28 families reported good or excellent gluten-free diet adherence. CONCLUSIONS: This novel study of children with CD identified through a mass screening program demonstrated improvement in symptoms, quality of life, and iron deficiency after 1 year follow-up evaluation. This demonstrates that there may be benefit to CD mass screening.

Effects of follicle-stimulating hormone on energy balance and tissue metabolic health after loss of ovarian function.

Loss of ovarian function imparts increased susceptibility to obesity and metabolic disease. These effects are largely attributed to decreased estradiol (E2), but the role of increased follicle-stimulating hormone (FSH) in modulating energy balance has not been fully investigated. Previous work that blocked FSH binding to its receptor in mice suggested this hormone may play a part in modulating body weight and energy expenditure after ovariectomy (OVX). We used an alternate approach to isolate the individual and combined contributions of FSH and E2 in mediating energy imbalance and changes in tissue-level metabolic health. Female Wistar rats were ovariectomized and given the gonadotropin releasing hormone (GnRH) antagonist degarelix to suppress FSH production. E2 and FSH were then added back individually and in combination for a period of 3 wk. Energy balance, body mass composition, and transcriptomic profiles of individual tissues were obtained. In contrast to previous studies, suppression and replacement of FSH in our paradigm had no effect on body weight, body composition, food intake, or energy expenditure. We did, however, observe organ-specific effects of FSH that produced unique transcriptomic signatures of FSH in retroperitoneal white adipose tissue. These included reductions in biological processes related to lipogenesis and carbohydrate transport. In addition, rats administered FSH had reduced liver triglyceride concentration (P < 0.001), which correlated with FSH-induced changes at the transcriptomic level. Although not appearing to modulate energy balance after loss of ovarian function in rats, FSH may still impart tissue-specific effects in the liver and white adipose tissue that might affect the metabolic health of those organs.NEW & NOTEWORTHY We find no effect of follicle-stimulating hormone (FSH) on energy balance using a novel model in which rats are ovariectomized, subjected to gonadotropin-releasing hormone antagonism, and systematically given back FSH by osmotic pump. However, tissue-specific effects of FSH on adipose tissue and liver were observed in this study. These include unique transcriptomic signatures induced by the hormone and a stark reduction in hepatic triglyceride accumulation.

Transnasal endoscopy ease score "TNEase score" to evaluate patient tolerance of unsedated transnasal endoscopy.

Transnasal endoscopy (TNE) with virtual reality (VR) distraction allows for unsedated pediatric upper endoscopy. Understanding the pediatric population that is successful with TNE is imperative for patient selection and experience. We developed a "TNEase Score" to assess patient tolerance from the physician's assessment. The aim of this study was to identify factors that influence patient's acceptance and tolerability of sedation-free TNE in pediatric patients undergoing the procedure. From March 2020 to April 2021, 110 TNEs were performed on subjects 5-22 years of age. The overall completion rate was 98.1%. Of these subjects, 66 subjects (60%) were graded by the gastroenterologist as TNEase Score 1 (with ease); 27 subjects (25%) were graded as TNEase Score 2 (minimal complaints); nine subjects (8%) were graded as TNEase score 3 (moderate complaints, required frequent reassurance); six subjects were graded as TNEase Score 4 (significant complaints and resistance); two subjects (2%) were graded as TNEase Score 5 (procedure terminated). Feasibility of TNE was significantly related to age, height, and whether the patient had undergone previous TNE. Thus, young age, shorter height, and first time TNE were significant predictors of higher TNEase score or difficulty tolerating TNE. Factors examined that did not predict higher TNEase score included gender, junior versus senior endoscopist, past medical history of anxiety, autism, attention-deficit/hyperactivity disorder (ADHD), or history of using a nasal spray at home. "TNEase score" allowed grading of the subject's experience and the majority of patients tolerated TNE with minimal complaints.

Natural Histories and Disease Complications in a Cohort of 151 Children With Gastric or Duodenal Eosinophilia.

INTRODUCTION: Eosinophilic gastritis (EoG) and duodenitis (EoD) are rare conditions that are poorly understood. Our aim was to describe the natural history of children with varying degrees of gastric or duodenal eosinophilia with respect to disease complications and histologic and endoscopic longitudinal trajectories. METHODS: The electronic medical record at a tertiary children's hospital was queried to identify patients with EoG, EoD, or EoG + EoD who were cared for between January 2010 and 2022. Multiple logistic regression was performed to explore associations between baseline features and persistence/recurrence of eosinophilia or complications remote from diagnosis. RESULTS: We identified 151 patients: 92 with EoG, 24 with EoD, 12 with EoG + EoD, and 23 with tissue eosinophilia but did not meet histologic criteria for EoG or EoD (low grade). The average age at diagnosis was 10.6 years, and average follow-up was 5.8 years. Twenty-five percent of patients with EoG or EoD had persistence/recurrence of eosinophilia; this was associated with increases in the EoG Endoscopic Reference Score (adjusted odds ratio [aOR] 1.34, confidence interval [CI] 1.03-1.74) on diagnostic endoscopy. Eighteen percent suffered from disease complications, and development of late complications was associated with presenting with a complication (aOR 9.63, CI 1.09-85.20), severity of duodenal endoscopic abnormalities (aOR 8.74, CI 1.67-45.60), and increases in the EoG Endoscopic Reference Score (aOR 1.70, CI 1.11-2.63). DISCUSSION: Patients with gastric and duodenal eosinophilia should be followed closely to monitor for recurrence and complications, especially those presenting with endoscopic abnormalities or complications.

Creative Arts Therapy Among Children With Cancer: Symptom Assessment Reveals Reduced Anxiety.

BACKGROUND: Symptom distress is related to decreased quality of life (QOL) among children with cancer, with high levels of pain, nausea, and anxiety reported. Creative arts therapy (CAT) has been related to improved QOL and symptoms in pediatric oncology, but the quality of evidence is mixed. OBJECTIVE: This article aims to examine the QOL symptom subscales in relation to CAT over time in children during the first year of cancer treatment. METHODS: A secondary analysis of prospective data was performed with linear mixed modeling on 267 observations with predictors of 2 groups: No CAT (n = 18) vs CAT (n = 65). The covariate of time (6 months) was used to explore the CAT relationship with the Pediatric Quality of Life Inventory (PedsQL) symptom subscales (pain and hurt, nausea, procedural anxiety, treatment anxiety, worry, cognitive problems, perceived physical appearance, and communication). RESULTS: Children (n = 83) were between 3 and 17 years old (M = 6), 51.2% female, and 32% minority. All tumor types were represented: liquid (37.3%), solid (24.1%), and central nervous system (38.6%). Reduced child report of procedural anxiety was significantly related to receiving CAT with a medium magnitude of association (adjusted effect size = 0.58, P = .01). CONCLUSION: Creative arts interventions were associated with a longitudinal improvement in anxiety in children with cancer. Further work is needed to target interventions to the appropriate specific burdensome symptoms. IMPLICATION FOR PRACTICE: Pediatric oncology nurses can advocate for CAT as an effective intervention to ameliorate the burdensome procedural anxiety experienced by patients.

The discriminatory ability of FibroScan liver stiffness measurement, controlled attenuation parameter, and FibroScan-aspartate aminotransferase to predict severity of liver disease in children.

Vibration controlled transient elastography (FibroScan) is used to predict the severity of liver fibrosis and steatosis. In pediatrics, few studies have been performed directly comparing liver histologic features with FibroScan liver stiffness measurements (LSMs) and controlled attenuation parameters (CAPs). The FibroScan-aspartate aminotransferase (FAST) score, which predicts liver disease severity in adult nonalcoholic fatty liver disease (NAFLD), has not been analyzed in children. The aims of this study were to determine if LSM and CAP correlated with liver histologic fibrosis stage and steatosis grade, respectively, and to determine the predictive capacity of FAST in pediatric NAFLD. Research participants (n = 216) included those with FibroScan within 90 days of a liver biopsy. The ability of LSM, CAP, and FAST to predict severity of liver disease was analyzed by Spearman correlation, linear regression, and receiver operating characteristic and C statistic. Significant correlations were identified between LSM and Ishak fibrosis stages, with the strongest correlation occurring in the non-NAFLD group (Spearman r = 0.47, p < 0.0001). LSM adequately predicted Ishak stages F0-2 versus F3-F6 (area under the receiver operating characteristic curve [AUROC], 0.73 for all; 0.77 for non-NAFLD). CAP strongly predicted histologic steatosis grade (r = 0.84; p < 0.0001; AUROC, 0.98). FAST had acceptable discriminatory ability for significant liver disease (AUROC, 0.75). A FAST cutoff ≥0.67 had a sensitivity of 89% but a specificity of only 62% at determining significant liver disease. This study encompasses one of the largest pediatric cohorts describing the accuracy of FibroScan LSM and CAP to predict liver histologic fibrosis stage and steatosis grade, respectively. In order to determine specific LSM, CAP, and FAST cut-off values for fibrosis stages, steatosis grades, and significant liver disease, respectively, a much larger cohort is necessary and will likely entail the need for multicentered studies.

Body mass index and variability in meal duration and association with rate of eating.

Background: A fast rate of eating is associated with a higher risk for obesity but existing studies are limited by reliance on self-report and the consistency of eating rate has not been examined across all meals in a day. The goal of the current analysis was to examine associations between meal duration, rate of eating, and body mass index (BMI) and to assess the variance of meal duration and eating rate across different meals during the day. Methods: Using an observational cross-sectional study design, non-smoking participants aged 18-45 years (N = 29) consumed all meals (breakfast, lunch, and dinner) on a single day in a pseudo free-living environment. Participants were allowed to choose any food and beverages from a University food court and consume their desired amount with no time restrictions. Weighed food records and a log of meal start and end times, to calculate duration, were obtained by a trained research assistant. Spearman's correlations and multiple linear regressions examined associations between BMI and meal duration and rate of eating. Results: Participants were 65% male and 48% white. A shorter meal duration was associated with a higher BMI at breakfast but not lunch or dinner, after adjusting for age and sex (p = 0.03). Faster rate of eating was associated with higher BMI across all meals (p = 0.04) and higher energy intake for all meals (p < 0.001). Intra-individual rates of eating were not significantly different across breakfast, lunch, and dinner (p = 0.96). Conclusion: Shorter beakfast and a faster rate of eating across all meals were associated with higher BMI in a pseudo free-living environment. An individual's rate of eating is constant over all meals in a day. These data support weight reduction interventions focusing on the rate of eating at all meals throughout the day and provide evidence for specifically directing attention to breakfast eating behaviors.

Macronutrient and Micronutrient Intake in Adolescents With Non-alcoholic Fatty Liver Disease: The Association With Disease Severity.

OBJECTIVES: While dietary changes are recommended to treat pediatric non-alcoholic fatty liver disease (NAFLD), the role of specific nutrients in disease progression is unclear. The objective of this study is to (1) assess the macronutrient and micronutrient intake in adolescents with liver biopsy proven NAFLD [with and without non-alcoholic steatohepatitis (NASH)] and lean controls; (2) determine nutritional predictors of disease severity amongst these groups. METHODS: Adolescents with biopsy-proven NAFLD and lean controls completed the Harvard Food Frequency Questionnaire. RESULTS: Twenty-eight NAFLD and 15 lean controls were studied. NAFLD with (n = 20) and without NASH (n = 8) had similar total calorie, protein, fat, and carbohydrate intake. Subjects with NASH had higher total sugar (122.3 ± 48.3 vs 83.1 ± 38.8 g), glucose (24.3 ± 9.3 vs 15.2 ± 7.5 g), sucrose (42.3 ± 16.9 vs 28.8 ± 11.7 g), and fructose (29.4 ± 12.5 vs 18.1 ± 8.0 g) intake than those with NAFLD but without NASH ( P < 0.05). Both NAFLD groups had similar micronutrient intake. Alanine aminotransferase (ALT) correlated with total caloric intake ( ρ = 0.4; P = 0.04). Total carbohydrate calories correlated with a higher NAS summary score ( ρ = 0.38; P = 0.04) and lobular inflammation ( ρ = 0.50; P = 0.007). Percent calories from added sugar and glucose correlated with worsening NAS summary score ( ρ = 0.44, P = 0.02; ρ = 0.48, P = 0.009) and lobular inflammation ( ρ = 0.51, P = 0.006; ρ = 0.53, P = 0.004). Percent calories from fructose correlated with lobular inflammation ( ρ = 0.56; P = 0.002). Total daily calories, protein, fat, carbohydrate, and micronutrient intake were similar between NAFLD and lean controls. CONCLUSIONS: NASH patients consume similar total calories, protein, and fat as those without NASH, but have significantly higher sugar intake. NAFLD and lean children, however, have similar macro/micronutrient intake. Histologic disease severity correlates with total carbohydrate and added sugar intake, supporting a role for simple sugar intake in NAFLD progression.

Anxiety and Depression in Pediatric Patients with Celiac Disease: A Large Cross-Sectional Study.

Mental health is a growing concern in pediatric celiac disease (CD). This study utilized the Revised Children's Anxiety and Depression Scale (RCADS) to investigate anxiety and depression symptom rates. Participants were children ages 8 to 17 years (M = 11.7, SD = 2.7; N = 175) with biopsy-proven CD (Median = 1.1 years post-diagnosis, IQR = 0-4) categorized into groups based on the child's age, caregiver or child respondent, presence or absence of comorbidities, and gluten-free diet duration. Self-reported RCADS scores showed 39% of children having clinically significant concerns for anxiety or depression ( P < 0.0001) but only 7% of caregiver-proxy RCADS scores indicated significant concerns for the child's anxiety and 14% for the child's depression. Rates of child-reported anxiety and depression symptoms were significantly higher for those without medical comorbidities than those with ( P = 0.04). Therefore, screening for mental health concerns, particularly anxiety and depression, should be routinely performed in pediatric patients with CD.

Quality of Life Outcomes With Creative Arts Therapy in Children With Cancer.

Introduction: Children with cancer experience distress and decreased quality of life (QOL). Creative arts therapy (CAT) is a therapeutic modality which may improve QOL. This study examined the relationship between CAT and QOL in children and adolescents with cancer. Secondary aims explored relationships between CAT and emotional reactions, resilience, and posture (to investigate future potential as an objective biomarker of QOL). Methods: Children aged 3-18 years undergoing cancer treatments and a parent proxy completed the PedsQL3.0 Cancer Module, Faces Scale for emotional reactions, Resilience Scale in adolescents (>12 years), and an inclinometer to measure thoracic kyphosis before and after CAT. CAT exposure (number of sessions) was recorded. Results: Ninety-eight children with cancer (mean age 7.8 years, range 3-17) and parent proxy were enrolled. Of the 83 participants included in the final analysis, 18 received no CAT, 32 received low dose, and 33 received high dose CAT. A significant improvement in QOL was seen with high dose CAT in (slope change, p = .015), but the overall time by group interaction was not significant. Slope change response patterns suggested that CAT led to improved posture as compared to no CAT (time by group interaction, p = .044). Discussion: CAT may be an effective intervention to improve QOL in this population. Because initial evidence suggests that posture also improves with CAT, further investigation of posture as a potential objective biomarker of QOL is supported. Further study with a randomized controlled trial is warranted.

Esophageal remodeling in eosinophilic esophagitis: Relationships to luminal captured biomarkers of inflammation and periostin.

BACKGROUND: Esophageal remodeling is a factor in disease progression and symptom severity for patients with eosinophilic esophagitis (EoE). Remodeling can begin early in children, resulting in stricture and food impaction. Detection of esophageal remodeling often depends on endoscopy and is appreciated only in its later stages. OBJECTIVE: We sought to determine whether luminal eosinophil-associated and remodeling proteins captured by the esophageal string test (EST) correlate with measures of esophageal remodeling and biomarkers of the epithelial-mesenchymal transition (EMT). METHODS: Patients with EoE (7-18 years old) were enrolled from 2 pediatric hospitals. Participants performed the EST and underwent endoscopy. Histology, distensibility measured by endoluminal functional lumen imaging probe, and symptoms were assessed. Protein quantitation by ELISA was performed on mucosal biopsy and EST samples. Tissue sections were evaluated for EMT. Outcome measures were summarized, and Spearman ρ was used to assess bivariate correlations. RESULTS: Forty patients (68% male) were enrolled (mean age, 12.5 years). Twenty-four (60%) had active disease (≥15 eosinophils per high-power field). EST-captured eotaxin-3, major basic protein 1, EDN, eosinophil peroxidase, and Charcot-Leyden crystal protein/galectin-10 showed significant correlations with peak eosinophils per high-power field (ρ 0.53-0.68, P < .001). Luminal proteins positively correlated with endoscopic features and markers of EMT, and negatively with esophageal distensibility. Periostin was captured by the EST and correlated with eosinophil density, basal zone hyperplasia, endoscopic appearance, and markers of EMT. CONCLUSION: Luminal markers of esophageal remodeling in addition to biomarkers of eosinophilic inflammation correlate with epithelial and functional remodeling in EoE.

Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms After Dilation in Adults With Eosinophilic Esophagitis.

BACKGROUND & AIMS: Esophageal dilation improves dysphagia but not inflammation in eosinophilic esophagitis (EoE) patients. We investigated if dilation modifies the association between symptoms and peak esophageal eosinophils per high-power field (eos/hpf). METHODS: Adults enrolled in a multisite prospective Consortium of Gastrointestinal Eosinophilic Disease Researchers Outcome Measures for Eosinophilic Gastrointestinal Diseases Across Ages observational study (NCT02523118) completed the symptom-based EoE activity index (EEsAI) patient-reported outcome instrument and underwent endoscopy with biopsy specimens. Patients were stratified based on dilation status as absent, performed 1 year or less before endoscopy, and performed more than 1 year before endoscopy. Assessments included Spearman correlations of the relationship between symptoms and eos/hpf and linear regression with EEsAI as the outcome, eos/hpf as predictor, and interaction for dilation and eos/hpf. RESULTS: Among 100 patients (n = 61 males; median age, 37 y), 15 and 40 patients underwent dilation 1 year or less and more than 1 year before index endoscopy, respectively. In nondilated patients, the association between eos/hpf and symptoms was moderate (ρ = 0.49; P < .001); for a 10-eos/hpf increase, the predicted EEsAI increased by 2.69 (P = .002). In patients dilated 1 or less and more than 1 year before index endoscopy, this association was abolished (ρ = -0.38; P = .157 for ≤1 y and ρ = 0.02; P = .883 >1 y); for a 10-eos/hpf increase, the predicted EEsAI changed by -1.64 (P = .183) and 0.78 (P = .494), respectively. Dilation modified the association between symptoms and eos/hpf (P = .005 and P = .187 for interaction terms of eos/hpf and dilation 1 or less years before and more than 1 year before index endoscopy, respectively). CONCLUSIONS: In nondilated EoE adults, eos/hpf correlate modestly with symptoms; this correlation was no longer appreciated in dilated patients, and the dilation effects lasted longer than 1 year. Dilation status should be considered in studies evaluating EoE treatment and for clinical follow-up evaluation.

Parent Perspectives on Exclusive Enteral Nutrition for the Treatment of Pediatric Crohn Disease.

OBJECTIVES: Exclusive enteral nutrition (EEN) is infrequently used in the United States but is an effective treatment for pediatric Crohn disease (CD). Limited data exists regarding patient and parent perspectives on this treatment modality. The aim of this study was to determine parent and provider perspectives regarding EEN and understand parent-cited barriers to its use. METHODS: We surveyed the parents/guardians of children ages 1 through 17 with CD in our institution regarding EEN. Healthcare provider perspectives regarding reason for stopping EEN and those cited by survey respondents were compared using retrospective chart review. RESULTS: One hundred fifteen (62.5%) out of 184 recipients responded to the survey. Ninety percentage of respondents had heard of EEN but of these, 26% had not discussed it with their gastroenterologist. Thirty-eight patients (33%) were treated in the past and 15 (13%) were currently on EEN. Common barriers cited by current EEN users were cost/finances and difficult social situations. Of the children who stopped EEN, most did so as parents felt it was not working (n = 14, 37%). In these cases, their primary gastroenterologist cited treatment failure for 4 cases and nonadherence for 6. CONCLUSIONS: Despite the efficacy of EEN and interest in dietary treatments by patients with CD, there are many barriers surrounding effective communication and successful implementation of dietary therapies. Future research is needed regarding patient-physician communication, cost mitigation, and coping with the social limitations of dietary therapies.

One-Hour Esophageal String Test: A Nonendoscopic Minimally Invasive Test That Accurately Detects Disease Activity in Eosinophilic Esophagitis.

OBJECTIVES: Eosinophilic esophagitis (EoE), a chronic food allergic disease, lacks sensitive and specific peripheral biomarkers. We hypothesized that levels of EoE-related biomarkers captured using a 1-hour minimally invasive Esophageal String Test (EST) would correlate with mucosal eosinophil counts and tissue concentrations of these same biomarkers. We aimed to determine whether a 1-hour EST accurately distinguishes active from inactive EoE or a normal esophagus. METHODS: In a prospective, multisite study, children and adults (ages 7-55 years) undergoing a clinically indicated esophagogastroduodenoscopy performed an EST with an esophageal dwell time of 1 hour. Subjects were divided into 3 groups: active EoE, inactive EoE, and normal esophageal mucosa. Eosinophil-associated protein levels were compared between EST effluents and esophageal biopsy extracts. Statistical modeling was performed to select biomarkers that best correlated with and predicted eosinophilic inflammation. RESULTS: One hundred thirty-four subjects (74 children, 60 adults) with active EoE (n = 62), inactive EoE (n = 37), and patient controls with a normal esophagus (n = 35) completed the study. EST-captured eosinophil-associated biomarkers correlated significantly with peak eosinophils/high-power field, endoscopic visual scoring, and the same proteins extracted from mucosal biopsies. Statistical modeling, using combined eotaxin-3 and major basic protein-1 concentrations, led to the development of EoE scores that distinguished subjects with active EoE from inactive EoE or normal esophagi. Eighty-seven percent of children, 95% of parents, and 92% of adults preferred the EST over endoscopy if it provided similar information. DISCUSSION: The 1-hour EST accurately distinguishes active from inactive EoE in children and adults and may facilitate monitoring of disease activity in a safe and minimally invasive fashion.

Nocturnal Hypoxia Activation of the Hedgehog Signaling Pathway Affects Pediatric Nonalcoholic Fatty Liver Disease Severity.

Chronic intermittent hypoxia and hedgehog (Hh) pathway dysregulation are associated with nonalcoholic fatty liver disease (NAFLD) progression. In this study, we determined the relationship between obstructive sleep apnea (OSA)/nocturnal hypoxia and Hh signaling in pediatric NAFLD. Adolescents with histologic NAFLD (n = 31) underwent polysomnogram testing, laboratory testing, and Sonic Hh (SHh), Indian hedgehog (IHh), glioblastoma-associated oncogene 2 (Gli2), keratin 7 (K7), α-smooth muscle actin (α-SMA), and hypoxia-inducible factor 1α (HIF-1α) immunohistochemistry. Aspartate aminotransferase (AST) correlated with SHh, r = 0.64; Gli2, r = 0.4; α-SMA, r = 0.55; and K7, r = 0.45 (P < 0.01), as did alanine aminotransferase (ALT) (SHh, r = 0.51; Gli2, r = 0.43; α-SMA, r = 0.51; P < 0.02). SHh correlated with NAFLD activity score (r = 0.39), whereas IHh correlated with inflammation (r = -0.478) and histologic grade (r = -0.43); P < 0.03. Subjects with OSA/hypoxia had higher SHh (4.0 ± 2.9 versus 2.0 ± 1.5), Gli2 (74.2 ± 28.0 versus 55.8 ± 11.8), and α-SMA (6.2 ± 3.3 versus 4.3 ± 1.2); compared to those without (P < 0.03). OSA severity correlated with SHh (r = 0.31; P = 0.09) and Gli2 (r = 0.37; P = 0.04) as did hypoxia severity, which was associated with increasing SHh (r = -0.53), Gli2 (r = -0.52), α-SMA (r = -0.61), and K7 (r = -0.42); P < 0.02. Prolonged O2 desaturations <90% also correlated with SHh (r = 0.55) and Gli2 (r = 0.61); P < 0.05. Conclusion: The Hh pathway is activated in pediatric patients with NAFLD with nocturnal hypoxia and relates to disease severity. Tissue hypoxia may allow for functional activation of HIF-1α, with induction of genes important in epithelial-mesenchymal transition, including SHh, and NAFLD progression.

Comparative Analysis of Adverse Events After Esophageal Balloon and Bougie Dilations in Children.

BACKGROUND: Pneumatic balloon and bougie dilation are widely used methods for pediatric esophageal dilation. There are no studies directly comparing the safety of these techniques in pediatric patients. This study compared adverse events (AEs) of balloon and bougie dilation in children at a single institution. METHODS: AEs were identified by means of a prospective clinical registry of all procedure related AEs from 2012 to 2015 at a single institution. Identified AEs underwent retrospective review of procedural and clinical details. The category of each AE was recorded and severity was assigned using a 5-point scoring system. AEs were compared between balloon and bougie dilation for different severities. RESULTS: There were 105 patients who underwent 246 dilation sessions. Balloon dilation was performed more commonly (n = 190, 77%) as compared to Maloney dilators (n = 56, 23%). Patients with balloon dilation were younger (3.0 vs 14.5 years, P = 0.0001) and more likely to have strictures from caustic ingestion (42% vs 2%, P < 0.0001) or surgical anastomoses (34% vs 5% P < 0.0001). Bougie dilation was used more commonly in patients with eosinophilic esophagitis (77% vs 7%, P < 0.0001)). In multivariate analysis, each year of increasing age was associated with a 12% increase in any AEs (P = 0.015), but no difference in clinically significant AEs (grade 2 or higher) was identified between dilation methods. CONCLUSIONS: Bougie and balloon dilation did not have significant differences in AE rates, but the patient populations differed between the 2 methods. The dilation method should depend on stricture characteristics and endoscopist expertise with each method.

Relative phase measures of intersegmental coordination describe motor control impairments in children with cerebral palsy who exhibit stiff-knee gait.

BACKGROUND: The purpose of this retrospective study was to explore lower limb intersegmental coordination as a clinically important indicator of motor control mechanisms in individuals with cerebral palsy exhibiting stiff-knee gait. We used the relative phase of thigh and foot segments around foot-off to describe motor control, given the relevance of the pre-swing phase of gait to the existence of stiff-knee gait. METHODS: Traditional gait parameters and thigh/foot intersegmental coordination were calculated using pre-and postoperative kinematic data from a cohort of 54 subjects (92 legs) with spastic cerebral palsy. All participants had stiff-knee gait, walked without assistive devices, and underwent rectus femoris transfer surgery to improve swing period knee flexion. Analyses included correlations between a) preoperative intersegmental coordination and gait variables (knee flexion range, rate and gait performance) and b) pre-to-postoperative intersegmental coordination change and change in gait variables. FINDINGS: Thigh/foot intersegmental coordination significantly (P < 0.001) correlated with knee flexion range, rate and walking speed. Postoperative intersegmental coordination was significantly more uncoupled than preoperative. Pre-to-postoperative intersegmental coordination improvement also significantly correlated with improvements in knee flexion range, rate and walking speed. Pre-to-postoperative changes in intersegmental coordination accounted for 43% and 36% of variance in knee flexion range change and knee flexion rate change respectively. INTERPRETATION: Intersegmental coordination is a clinically important factor in knee flexion limitations associated with stiff-knee gait for individuals with cerebral palsy. These findings are a foundation for further study of intersegmental coordination measures as complements to traditional instrumented gait analysis.

Alignment of parent- and child-reported outcomes and histology in eosinophilic esophagitis across multiple CEGIR sites.

BACKGROUND: Patient-reported outcome metrics for eosinophilic esophagitis (EoE) have been developed and validated but not used in a multicenter pediatric population or systematically aligned with histology. OBJECTIVE: We sought to understand (1) the potential of caregiver report to predict patient self-reported symptoms and (2) the correlation of patient-reported outcome domains with histology. METHODS: Patients with EoE (n = 310) and their parents participating in the Consortium of Gastrointestinal Eosinophilic Disease Researchers (CEGIR) observational clinical trial were queried for baseline patient symptoms and quality of life (QOL) by using the Pediatric Eosinophilic Esophagitis Symptom Score, version 2 (PEESSv2.0), and the Pediatric QOL EoE module (PedsQL-EoE), and biopsy specimens were analyzed by using the EoE Histology Scoring System. RESULTS: PEESSv2.0 parental and child reports aligned across all domains (r = 0.68-0.73, P < .001). PedsQL-EoE reports correlated between parents and children across ages and multiple domains (r = 0.48-0.79, P < .001). There was a tight correlation between symptoms on PEESSv2.0 and their effects on QOL both on self-report and parental report (P < .001). Self-reported symptoms on PEESSv2.0 (positively) and PedsQL-EoE (inversely) showed a weak correlation with proximal, but not distal, peak eosinophil counts and features and architectural tissue changes on the EoE Histology Scoring System (P < .05). CONCLUSIONS: Parents of children with EoE aged 3 to 18 years accurately reflected their children's disease symptoms and QOL. Self- and parent-reported symptoms correlate with proximal esophageal histology. Our data suggest that parental report in young children can function as an adequate marker for self-reported symptoms and that self-reported symptoms can reflect changes in tissue histology in the proximal esophagus. These findings should be considered during clinical trials for drug development.

Treating Obstructive Sleep Apnea and Chronic Intermittent Hypoxia Improves the Severity of Nonalcoholic Fatty Liver Disease in Children.

OBJECTIVE: To determine the effects of treating obstructive sleep apnea/nocturnal hypoxia on pediatric nonalcoholic fatty liver disease (NAFLD) severity and oxidative stress. STUDY DESIGN: Biopsy proven participants (n = 9) with NAFLD and obstructive sleep apnea/hypoxia were studied before and after treatment with continuous positive airway pressure (CPAP) for sleep disordered breathing, including laboratory testing and markers of oxidative stress, urine F(2)-isoprostanes. RESULTS: Adolescents (age 11.5 ± 1.2 years; body mass index, 29.5 ± 3.8 kg/m2) with significant NAFLD (mean histologic necroinflammation grade, 2.3 ± 0.9; fibrosis stage, 1.4 ± 1.3; NAFLD Activity Score summary, 4.8 ± 1.6) had obstructive sleep apnea/hypoxia by polysomnography. At baseline, they had severe obstructive sleep apnea/hypoxia, elevated aminotransferases, the metabolic syndrome, and significant oxidative stress (high F(2)-isoprostanes). Obstructive sleep apnea/hypoxia was treated with home CPAP for a mean 89 ± 62 days. Although body mass index increased, obstructive sleep apnea/hypoxia severity improved on CPAP and was accompanied by reduced alanine aminotransferase, metabolic syndrome markers, and F(2)-isoprostanes. CONCLUSIONS: This study provides strong evidence that treatment of obstructive sleep apnea/nocturnal hypoxia with CPAP in children with NAFLD may reverse parameters of liver injury and reduce oxidative stress. These data also suggest CPAP as a new therapy to prevent progression of NAFLD in those children with obesity found to have obstructive sleep apnea/nocturnal hypoxia.