Identifying collagen VI as a target of fibrotic diseases regulated by CREBBP/EP300.

Fibrotic diseases remain a major cause of morbidity and mortality, yet there are few effective therapies. The underlying pathology of all fibrotic conditions is the activity of myofibroblasts. Using cells from freshly excised disease tissue from patients with Dupuytren's disease (DD), a localized fibrotic disorder of the palm, we sought to identify new therapeutic targets for fibrotic disease. We hypothesized that the persistent activity of myofibroblasts in fibrotic diseases might involve epigenetic modifications. Using a validated genetics-led target prioritization algorithm (Pi) of genome wide association studies (GWAS) data and a broad screen of epigenetic inhibitors, we found that the acetyltransferase CREBBP/EP300 is a major regulator of contractility and extracellular matrix production via control of H3K27 acetylation at the profibrotic genes, ACTA2 and COL1A1 Genomic analysis revealed that EP300 is highly enriched at enhancers associated with genes involved in multiple profibrotic pathways, and broad transcriptomic and proteomic profiling of CREBBP/EP300 inhibition by the chemical probe SGC-CBP30 identified collagen VI (Col VI) as a prominent downstream regulator of myofibroblast activity. Targeted Col VI knockdown results in significant decrease in profibrotic functions, including myofibroblast contractile force, extracellular matrix (ECM) production, chemotaxis, and wound healing. Further evidence for Col VI as a major determinant of fibrosis is its abundant expression within Dupuytren's nodules and also in the fibrotic foci of idiopathic pulmonary fibrosis (IPF). Thus, Col VI may represent a tractable therapeutic target across a range of fibrotic disorders.

Explainable AI and machine learning: performance evaluation and explainability of classifiers on educational data mining inspired career counseling.

Machine Learning concept learns from experiences, inferences and conceives complex queries. Machine learning techniques can be used to develop the educational framework which understands the inputs from students, parents and with intelligence generates the result. The framework integrates the features of Machine Learning (ML), Explainable AI (XAI) to analyze the educational factors which are helpful to students in achieving career placements and help students to opt for the right decision for their career growth. It is supposed to work like an expert system with decision support to figure out the problems, the way humans solve the problems by understanding, analyzing, and remembering. In this paper, the authors have proposed a framework for career counseling of students using ML and AI techniques. ML-based White and Black Box models analyze the educational dataset comprising of academic and employability attributes that are important for the job placements and skilling of the students. In the proposed framework, White Box and Black Box models get trained over an educational dataset taken in the study. The Recall and F-Measure score achieved by the Naive Bayes for performing predictions is 91.2% and 90.7% that is best compared to the score of Logistic Regression, Decision Tree, SVM, KNN, and Ensemble models taken in the study.

Lubiprostone for Pediatric Functional Constipation: Randomized, Controlled, Double-Blind Study With Long-term Extension.

BACKGROUND & AIMS: Pediatric functional constipation (PFC) is a common problem in children that causes distress and presents treatment challenges to health care professionals. We conducted a randomized, placebo-controlled trial (study 1) in patients with PFC (6-17 years of age) to evaluate the efficacy and safety of lubiprostone, followed by an open-label extension for those who completed the placebo-controlled phase (study 2). METHODS: Study 1 (NCT02042183) was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 12-week study evaluating the efficacy and safety of lubiprostone 12 µg twice daily (BID) and 24 µg BID. Study 2 (NCT02138136) was a phase 3, long-term, open-label extension of study 1. In both studies, lubiprostone doses were based on patients' weight. Efficacy was assessed solely based on study 1, with a primary endpoint of overall spontaneous bowel movement (SBM) response (increase of ≥1 SBM/wk vs baseline and ≥3 SBMs/wk for ≥9 weeks, including 3 of the final 4 weeks). RESULTS: 606 patients were randomized to treatment (placebo: n = 202; lubiprostone: n = 404) in study 1. No statistically significant difference in overall SBM response rate was observed between the lubiprostone and placebo groups (18.5% vs 14.4%; P = .2245). Both the 12-µg BID and 24-µg BID doses of lubiprostone were well tolerated in the double-blind and extension phases, with a safety profile consistent with that seen in adult studies. CONCLUSIONS: Lubiprostone did not demonstrate statistically significant effectiveness over placebo in children and adolescents with PFC but did demonstrate a safety profile similar to that in adults. (ClinicalTrials.gov: Number: NCT02042183; Number: NCT02138136).

Efficacy of Auricular Neurostimulation in Adolescents With Irritable Bowel Syndrome in a Randomized, Double-Blind Trial.

BACKGROUND & AIMS: Auricular neurostimulation therapy, in which a noninvasive device delivers percutaneous electrical nerve field stimulation (PENFS) to the external ear, is effective in pediatric patients with functional abdominal pain disorders. Preclinical studies showed that PENFS modulates central pain pathways and attenuates visceral hyperalgesia. We evaluated the efficacy of PENFS in adolescents with irritable bowel syndrome (IBS). METHODS: We analyzed data from pediatric patients with IBS who participated in a double-blind trial at a tertiary care gastroenterology clinic from June 2015 through November 2016. Patients were randomly assigned to groups that received PENFS (n = 27; median age, 15.3 y; 24 female) or a sham stimulation (n = 23; median age, 15.6 y; 21 female), 5 days/week for 4 weeks. The primary endpoint was number of patients with a reduction of 30% or more in worst abdominal pain severity after 3 weeks. Secondary endpoints were reduction in composite abdominal pain severity score, reduction in usual abdominal pain severity, and improvement in global symptom based on a symptom response scale (-7 to +7; 0 = no change) after 3 weeks. RESULTS: Reductions of 30% or more in worst abdominal pain were observed in 59% of patients who received PENFS vs 26% of patients who received the sham stimulation (P = .024). The patients who received PENFS had a composite pain median score of 7.5 (interquartile range [IQR], 3.6-14.4) vs 14.4 for the sham group (IQR, 4.5-39.2) (P = .026) and a usual pain median score of 3.0 (IQR, 3.0-5.0) vs 5.0 in the sham group (IQR, 3.0-7.0) (P = .029). A symptom response scale score of 2 or more was observed in 82% of patients who received PENFS vs 26% of patients in the sham group (P ≤ .001). No significant side effects were reported. CONCLUSIONS: Auricular neurostimulation reduces abdominal pain scores and improves overall wellbeing in adolescents with IBS. PENFS is a noninvasive treatment option for pediatric patients with functional bowel disorders. ClinicalTrials.gov no: NCT02367729.

Proceedings of the 2018 Advances In Motility and In NeuroGastroenterology: AIMING for the Future Single Topic Symposium.

OBJECTIVES: Motility and functional disorders are common in children and often debilitating, yet these disorders remain challenging to treat effectively. At the 2018 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the Neurogastroenterology and Motility Committee held a full day symposium entitled, 2018 Advances In Motility and In NeuroGastroenterology - AIMING for the future. The symposium aimed to explore clinical paradigms in pediatric gastrointestinal motility disorders and provided a foundation for advancing new scientific and therapeutic research strategies. METHODS: The symposium brought together leading experts throughout North America to review the state of the art in the diagnosis and management of motility and functional disorders in children. Presentations were divided into esophageal, antral duodenal, and colorectal modules. Each module included oral presentations by experts in the respective fields, leading to thought-provoking discussions. There were 2 breakout sessions with small group discussions on select topics, focusing on defining scientific insights into the diagnosis and management of pediatric functional gastrointestinal and motility disorders in a systematic, segment-based approach. CONCLUSIONS: The field of neurogastroenterology has made remarkable progress in the last decade. The current report summarizes the major learning points from the symposium highlighting the diagnosis and promising therapies on the horizon for pediatric neurogastrointestinal and motility disorders.

Group Treatment of Fecal Incontinence: A Description of an Interdisciplinary Intervention.

INTRODUCTION: Approximately 5% of children in the United States have chronic fecal incontinence. Unfortunately, standard medical management of fecal incontinence fails in 20% to 60% of cases. A combined medical-behavioral model is often recommended in these cases. The purpose of this pilot study was to describe an interdisciplinary group-based treatment for fecal incontinence in school-aged children, and to present a description of changes in treatment adherence rates that affect clinical effectiveness. METHOD: Poop group employed a developmentally appropriate model of care in which caregivers and children participated in separate but simultaneously held therapy groups. This interdisciplinary 6-week protocol is designed to increase appropriate stooling, decrease soiling events, and increase medication adherence pre- to post-treatment. Group sessions focus on the GI system, medication, toilet sitting posture, hydration, fiber, and behavior contracts. In addition, participant families consult with an Advanced Nurse Practitioner privately at each session discussing symptoms and making medication modifications as needed. RESULTS: Nineteen families completed the 6-week protocol. Appropriate stool frequency was improved (P ≤ 0.01), and soiling was reduced (P ≤ 0.00). Medication adherence was also improved (P ≤ 0.04). Treatment results were maintained at 1-month follow-up. DISCUSSION: A developmentally targeted intervention and interdisciplinary focus of treatment likely account for treatment successes. CONCLUSION: Poop group may be an effective interdisciplinary treatment option for families of children who fail traditional outpatient treatment.

Pediatric Intestinal Pseudo-obstruction in the Era of Genetic Sequencing.

PURPOSE OF REVIEW: The purpose of this review is to discuss current knowledge on pediatric intestinal pseudo-obstruction. We will also review new mutations that have been identified through advancement in genetic testing, allowing for a better understanding of the underlying mechanisms of intestinal dysmotility and potential etiologies. RECENT FINDINGS: With the advancements in genetic testing, new mutations have been identified in the diagnosis of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), a disorder leading to pediatric pseudo-obstruction. MYLK, LMOD1, MYL9, and MYH11 encode for various proteins within smooth muscle cells; abnormalities within these proteins lead to abnormal intestinal smooth muscle contractions. Chronic intestinal pseudo-obstruction (CIPO) is defined by symptoms of bowel obstruction in the absence of a lumen-occluding lesion. CIPO is a heterogeneous group of disorders caused by abnormalities in the enteric neurons, intestinal smooth muscle, and/or the interstitial cells of Cajal (ICC). Symptoms can be non-specific and etiologies include both primary and secondary causes of CIPO that contribute to the delay in recognizing this condition and making the correct diagnosis. Chronic intestinal pseudo-obstruction has been recognized in both adults and children with fundamental differences in the etiology, symptom onset, clinical features and natural history of this disorder. For this reason, it has been considered a separate entity referred to as pediatric intestinal pseudo-obstruction (PIPO).

Healthcare Utilization and Comorbidities Associated with Anorectal Malformations in the United States.

OBJECTIVE: To determine nationwide prevalence and healthcare utilization in children with anorectal malformations and associated anomalies over a 6-year period. STUDY DESIGN: We used the Kids' Inpatient Database for the years 2006, 2009, and 2012 for data collection. International Classification of Diseases, Ninth Revision codes were used to identify patients with anorectal malformations and associated anomalies. RESULTS: A total of 2396 children <2 years of age with anorectal malformations were identified using weighted analysis; 54.3% of subjects were male. The ethnic subgroups were 40.1% white, 23.6% Hispanic, 9.3% African American, and 27% other ethnicity. Other congenital anomalies were reported in 80% of anorectal malformations and were closely associated with increased length of stay and costs. A genetic disorder was identified in 14.1% of the sample. Urogenital anomalies were present in 38.5%, heart anomalies in 21.2%, and 8.6% had vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula and/or esophageal atresia, renal anomalies, and limb defects association. Anorectal malformations with other anomalies including vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula and/or esophageal atresia, renal anomalies, and limb defects association incurred significant hospital charges when compared with anorectal malformations alone. The average annual healthcare expenditure for surgical correction of anorectal malformations and associated anomalies for the 3 years was US $45.5 million. CONCLUSIONS: This large, major nationally representative study shows that majority of children with anorectal malformations have additional congenital anomalies that deserve prompt recognition. The high complexity and need for lifelong multidisciplinary management is associated with substantial healthcare expenditure. This information complements future healthcare resource allocation and planning for management of children with anorectal malformations.

Trends of Cholecystectomies for Presumed Biliary Dyskinesia in Children in the United States.

BACKGROUND: Biliary dyskinesia (BD) is a controversial clinical entity. Standardized diagnostic test and management guidelines are lacking in children. Published data suggest that long-term outcomes of surgical and medical management are similar. We sought to determine national population-based trends of cholecystectomies performed in children for BD and associated healthcare expenditure in the United States during a 10-year period. METHODS: Using Nationwide Inpatient Sample and the International Classification of Diseases, the 9th revision clinical modification codes, we identified children who had a cholecystectomy for BD from 2002 to 2011 in the United States. RESULTS: A total of 66,380 cholecystectomies were identified as primary procedural diagnosis using weighted analysis from 2002 to 2011 in children. BD was the primary indication for cholecystectomy in 6674 (10.8%) of the patients. During the study period, the number of cholecystectomies performed for BD in children increased from 6.6% in 2002 to 10.6% in 2011, and a majority were adolescent white females. The annual health care expenditure for surgical management of BD for children in the US was estimated to almost $16 million/year. CONCLUSIONS: Despite lack of standardized diagnostic criteria and variable outcomes of surgical intervention reported in pediatric literature, cholecystectomies are commonly performed for children with BD in the United States. Consensus guidelines for the diagnosis and management of this controversial disorder in children are needed.

Cyclic Vomiting Syndrome in Children and Adults: What Is New in 2018?

PURPOSE OF REVIEW: Cyclic vomiting syndrome (CVS) is a disabling functional gastrointestinal disorder characterized by severe vomiting episodes that alternate with symptom-free periods. The purpose of this review is to summarize current knowledge and highlight most recent data on prevalence, diagnosis, management, and impact of CVS in children and adults. RECENT FINDINGS: Originally thought to be a pediatric disorder, the past decade has witnessed a considerable increase in CVS diagnosed in adults. Despite improved recognition of CVS, without a delineated pathophysiology and specific biomarker, it remains classified as a functional gastrointestinal disorder. Migraines and CVS share a common pathway based on several studies and response to migraine therapy. Recent work has begun to expand the list of comorbidities and identify plausible mechanisms and new therapeutic avenues. This review seeks to highlight best practices and novel therapies for CVS based on expert consensus and review of available literature.

Chronic Intestinal Pseudo-obstruction.

Chronic intestinal pseudo-obstruction (CIP) is defined by either continuous or intermittent symptoms of bowel obstruction in the absence of fixed lumen excluding lesion. CIP includes a heterogeneous group of disorders which result either from diseases affecting the enteric neurons and smooth muscle lining or those involving the autonomic innervation of the bowel. Symptoms associated with CIP are nonspecific, which can sometimes contribute to the delay in recognizing the condition and making the correct diagnosis. The diagnostic workup should include imaging and manometry studies and, occasionally, full-thickness bowel biopsies for histopathological examination may be required. Multidisciplinary team approach for the management of these patients is recommended, and the team members should include a gastroenterologist, surgeon, chronic pain specialist, clinical nutritionist, and a psychologist. The treatment goals should include optimizing the nutritional status and preventing or delaying the development of intestinal failure. The majority of the patients require enteral or parenteral nutrition support, and chronic pain is a common and distressing symptom. Small bowel transplantation may be required if patients develop liver complications due to parenteral nutrition, have difficult central line access, or have poor quality of life and worsening pain despite aggressive medical management.

Reduced Functional Connectivity Between the Hypothalamus and High-order Cortical Regions in Adolescent Patients With Irritable Bowel Syndrome.

The hypothalamus plays a critical role in maintaining visceral homeostasis. Altered hypothalamus activation has been implicated in functional gastrointestinal disorders, including irritable bowel syndrome (IBS). One important aspect of homeostatic regulation is the cortical modulation of limbic and paralimbic subsystems, including the hypothalamus, which in turn affects the descending regulatory processes mediating visceral homeostasis. Using neuroimaging, we evaluated hypothalamus functional connectivity in adolescent patients with IBS and age-matched healthy controls who received rectal distension stimulations. More extensive hypothalamus connectivity was observed in liminal than subliminal condition in controls, but not in patients with IBS. Compared with controls, patients with IBS showed significantly reduced hypothalamus connectivity in the bilateral prefrontal cortices, supplementary motor and premotor areas, bilateral sensorimotor cortex, and limbic subareas, which are specifically involved in homeostatic regulation. The findings support the generalized homeostatic regulation model that reduced cortical and limbic modulations of hypothalamus functioning underlies disrupted visceral homeostasis in patients with IBS.

Empirically Derived Patterns of Pain, Stooling, and Incontinence and Their Relations to Health-Related Quality of Life Among Youth With Chronic Constipation.

Objective: Chronic constipation is associated with pain, stress, and fecal incontinence, which negatively impact health-related quality of life (HRQoL); however, it is unclear if patterns of pain, stool frequency, and incontinence are differentially associated with HRQoL in youth with chronic constipation. Methods: 410 caregivers completed a demographics and symptoms form, the Parental Opinions of Pediatric Constipation, Pediatric Symptom Checklist, and the Functional Disability Inventory. Results: Stooling patterns were derived using Latent Variable Mixture Modeling. A three-class model emerged: withholding/avoiding ( WA ), pain , and fecal incontinence ( FI ). The pain class reported the greatest amount of disease burden/distress, greatest impairments in illness-related activity limitations, more psychosocial problems, and, along with the FI class, elevated levels of family conflict. The FI class reported the greatest amount of parental worry of social impact. Conclusions: Youth with chronic constipation who experience pain or fecal incontinence may be at a greater risk for specific HRQoL problems such as illness-related activity limitations, psychosocial issues, disease burden and worry, and family conflict.

A multicenter study on childhood constipation and fecal incontinence: effects on quality of life.

OBJECTIVE: To describe the effects of childhood functional constipation compared with functional constipation plus fecal incontinence on quality of life, evaluating effects on physical, psychosocial, and family functioning. STUDY DESIGN: This prospective, multicenter study collected data from 5 regional children's hospitals. Children meeting Rome III criteria for functional constipation were included. Parents completed the following 5 instruments: Pediatric Quality of Life Inventory (PedsQL), PedsQL-Family Impact Module, Functional Disability Inventory-Parent Version, Pediatric Inventory for Parents (PIP), and Pediatric Symptom Checklist-Parent Report. RESULTS: Families of 410 children aged 2-18 years (mean [SD], 7.8 [3.5] years; 52% male) were included. Children with functional constipation+fecal incontinence had worse quality of life than children with functional constipation alone (PedsQL Total Score, P ≤ .03). Older children with functional constipation + fecal incontinence had lower quality of life than their younger counterparts (PedsQL Total Score, P ≤ .047). Children with functional constipation+fecal incontinence had worse family functioning (PedsQL-Family Impact Module Total Score, P ≤ .012), greater parental stress (PIP-F Total Score, P ≤ .016; PIP-D Total Score, P ≤ .013), and poorer psychosocial functioning (Pediatric Symptom Checklist Total Score, P ≤ .003). There were no statistically significant between-group differences in physical functioning based on the functional Disability Inventory. CONCLUSION: Fecal incontinence significantly decreases quality of life compared with functional constipation alone in children. Older children with functional constipation+fecal incontinence may be at particular risk. Strategies for early identification and treatment of constipation along with diagnosis and treatment of related adjustment difficulties may mitigate the negative impact of this highly prevalent condition.

Measuring Health-Related Quality of Life With the Parental Opinions of Pediatric Constipation Questionnaire.

OBJECTIVES: The purpose of this study was to develop a caregiver-completed constipation condition-specific health-related quality of life (HRQL) instrument. METHODS: 410 caregivers of children aged 2-18 years completed the Parental Opinions of Pediatric Constipation (POOPC), the PedsQL Generic Core Scales, PedQL Family Impact Module, Pediatric Symptom Checklist, the Functional Disability Inventory, the Pediatric Inventory for Parents, and a demographic questionnaire. Exploratory and confirmatory factor analyses were conducted to assess the psychometric properties of the POOPC. RESULTS: Analyses yielded four factors called Parental Burden/Distress, Family Conflict, Difficulties with the Medical Team, and Worry about Social Impact that reflect problems in HRQL secondary to constipation and soiling, which were generally more strongly correlated with similar measures relative to a general measure of youth's psychosocial functioning. CONCLUSION: The POOPC is a psychometrically sound measure, which may be useful to clinicians and researchers identifying domains of treatment needs for children and their families.

Joint hypermobility: a common association with complex functional gastrointestinal disorders.

OBJECTIVE: To evaluate the prevalence of joint hypermobility (JH) and comorbid conditions in children and young adults referred to a tertiary care neurogastroenterology and autonomic disorders clinic for functional gastrointestinal complaints. STUDY DESIGN: This was a retrospective chart review of 66 new patients aged 5-24 years who fulfilled at least 1 pediatric Rome III criteria for a functional gastrointestinal disorder (FGID) and had a recorded Beighton score (n = 45) or fibromyalgia tender point score (n = 45) based on physician examination. Comorbid symptoms were collected and autonomic testing was performed for evaluation of postural tachycardia syndrome (POTS). RESULTS: The median patient age was 15 years (range, 5-24 years), 48 (73%) were females, and 56% had JH, a significantly higher rate compared with population studies of healthy adolescents (P < .001; OR, 10.03; 95% CI, 5.26-19.13). POTS was diagnosed in 34% of patients and did not correlate significantly with hypermobility. Comorbid conditions were common, including sleep disturbances (77%), chronic fatigue (93%), dizziness (94%), migraines (94%), chronic nausea (93%), and fibromyalgia (24%). CONCLUSION: JH and other comorbid symptoms, including fibromyalgia, occur commonly in children and young adults with complex FGIDs. POTS is prevalent in FGIDs but is not associated with hypermobility. We recommend screening patients with complex FGIDs for JH, fibromyalgia, and comorbid symptoms such as sleep disturbances, migraines, and autonomic dysfunction.

Comparison of light and electron microscopy in measurement of esophageal intercellular space in children.

OBJECTIVES: A good objective marker of esophageal mucosal damage from gastroesophageal reflux disease (GERD) is lacking in children. Increased esophageal epithelial intercellular (EEIC) space measured using electron microscopy (EM) has been proposed as a surrogate of esophageal mucosal damage in adults with GERD. The aim of the present study was to compare EEIC space measured using EM and light microscopy (LM) in children with nonerosive reflux disease (NERD) with asymptomatic controls. METHODS: Distal esophageal mucosal biopsy was used to measure EEIC space using EM in 35 NERD subjects and 8 controls. In a subset of these patients we used phase contrast LM to measure EEIC space area (26 NERD subjects and 8 controls). RESULTS: The median (range) EEIC space measured using EM in the NERD group was 1.15 (0.74-1.64) µm compared with 0.93 (0.67-1.11) µm in the control group (P = 0.002). The median (range) EEIC space measured using LM was 14.4% (9.6%-26.3%) in the NERD group and 9.6% (8.5%-17.2%) in controls (P = 0.003). Using a cutoff value of 1.02 µm for normal EEIC space measured by EM, we obtained 73% sensitivity and 75% specificity to distinguish the NERD group from the control group, and using a cutoff value of 11.1% for EEIC space measured by LM, we obtained 96% sensitivity and 75% specificity. CONCLUSIONS: EEIC space is increased in children with NERD compared with that in controls, suggesting that changes in EEIC space can be a useful marker of esophageal mucosal injury in children with NERD. Our results suggest that the accuracy of EM and LM to evaluate EEIC space changes in NERD is comparable, and LM may be a more cost-effective option.

Colon high-resolution manometry: using pressure topography plots to evaluate pediatric colon motility.

OBJECTIVES: Colon manometry is usually performed using the 8-pressure sensor water-perfused manometry system. High-resolution manometry (HRM), using closely spaced solid-state pressure recording sensors, provides more detailed information of gut luminal pressure changes, and, by displaying the HRM data as a pressure topography plot (PTP), helps with data interpretation. Our aim was to compare the colon and rectal luminal pressure data obtained using 8 pressure sensors and displayed as conventional line plot (CLP) with data obtained using a custom-made solid state manometry catheter with 36 pressure recording sensors and displayed as PTP. METHODS: We evaluated colon manometry patterns during fasting, response to meal, and bisacodyl stimulation in 10 patients with constipation and stool expulsion disorders. The data from 8 pressure sensors were displayed as CLP and data from 36 pressure sensors as PTP. Two gastroenterologists independently interpreted these studies. We calculated variability in interpreting colon, rectal, and anal manometry data. RESULTS: Intermode, interobserver, and intraobserver reliability were good to excellent for recognizing colon contraction patterns when data are displayed as PTP compared with when displayed as CLP, whereas the reliability for recognizing anal contractions were poor to excellent. CONCLUSIONS: Colonic and anal manometry patterns are easily recognized when HRM data are expressed as PTP. Obtaining information of colonic luminal pressure changes with rectum and anal pressure changes using HRM can help better understand the pathophysiology of pediatric constipation and stool expulsion disorders.

Red flags in children with chronic abdominal pain and Crohn's disease-a single center experience.

OBJECTIVE: To compare history and symptoms at initial presentation of patients with chronic abdominal pain (CAP) and Crohn's disease (CD). Red flags are used to help determine which patients with CAP are likely to have an underlying disease such as CD. However, red flags have not been validated and pediatric studies are lacking. STUDY DESIGN: Patients seen in the outpatient Pediatric Gastroenterology Clinic at Children's Hospital of Wisconsin between 2005 and 2008 prospectively completed a demographic, history, and symptom questionnaire. Patients with abdominal pain for at least 1 month and no evidence of organic disease were compared with patients diagnosed with CD confirmed by mucosal biopsies. RESULTS: Data were collected on 606 patients (128 with CD and 478 with functional gastrointestinal disorders). Patients with functional gastrointestinal disorders had more stressors (P < .001), were more likely to have a positive family history of irritable bowel syndrome, reflux, or constipation (P < .05), were more likely to have vomiting but less likely to have hematochezia, weight loss, and problems gaining weight (P < .05); wake from sleep and joint pain were no different between groups. Anemia, hematochezia, and weight loss were most predictive of CD (cumulative sensitivity of 94%). CONCLUSION: The presence of anemia, hematochezia, and weight loss help identify patients with CAP who require further work-up and referral to a pediatric gastroenterologist. Furthermore, waking from sleep or joint pain occurred similarly between groups and should not be considered as "red flags."