[Show abstract][Hide abstract] ABSTRACT: Studies indicate a close relationship between Yersinia and Crohn's disease in adults. Our study tested 77 colonic specimens from children with Crohn's disease for the presence of Yersinia DNA using a validated polymerase chain reaction (PCR) assay. Control cases included specimens from 45 ulcerative colitis patients and 10 appendicitis patients. The presence of Yersinia in Crohn's specimens was significant compared to the control specimens (9% vs. 0%; p = 0.0055). While our study supports the medical literature, future studies are needed to determine if the relationship between Crohn's disease and Yersinia is an initiating or mediating factor in the pathogenesis of pediatric Crohn's disease.
Fetal and pediatric pathology 04/2013; · 0.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES:: Few clinical predictors are associated with definitive proctocolectomy in children with ulcerative colitis (UC). The purpose of this study was to identify clinical predictors associated with surgery in children with UC using a disease specific database. METHODS:: Children diagnosed with UC at age <18 y were identified using the Pediatric Inflammatory Bowel Disease Consortium (PediIBDC) database. Demographic and clinical variables from January 1999-November 2003 were extracted alongside incidence and surgical staging. RESULTS:: Review of the PediIBDC database identified 406 children with UC. Approximately half were female (51%) with an average age at diagnosis of 10.6±4.4 years in both boys and girls. Average follow-up was 6.8 (±4.0) years. Of the 57 (14%) who underwent surgery, median time to surgery was 3.8 (IQR 4.9) years after initial diagnosis. Children presenting with weight loss (HR 2.55, 99% CI 1.21-5.35) or serum albumin <3.5 g/dL (HR 6.05, 99% CI 2.15-17.04) at time of diagnosis, and children with a first-degree relative with UC (HR 1.81, 99% CI 1.25-2.61) required earlier surgical intervention. Furthermore, children treated with cyclosporine (HR 6.11, 99% CI 3.90-9.57) or tacrolimus (HR 3.66, 99% CI 1.60-8.39) also required earlier surgical management. Other symptoms, laboratory tests and medical therapies were not predictive for need of surgery. CONCLUSIONS:: Children with UC presenting with hypoalbuminemia, weight loss, a family history of UC and those treated with calcineurin inhibitors frequently require restorative proctocolectomy for definitive treatment. Early identification and recognition of these factors should be used to shape treatment goals and initiate multidisciplinary care at the time of diagnosis.
Journal of pediatric gastroenterology and nutrition 06/2012; · 2.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Helicobacter pylori infection is usually acquired in childhood, but little is known about its natural history in asymptomatic children, primarily due to the paucity of non-invasive diagnostic methods. H. pylori strains harboring cagA and specific alleles of hopQ and vacA are associated with increased risk for gastric cancer. Many studies of H. pylori virulence markers in children have the bias that symptomatic subjects are selected for endoscopy, and these children may harbor the most virulent strains. Our aim is to genotype cagA, hopQ, and vacA alleles in stool DNA samples of healthy Colombian children residing in an area with high incidence of gastric cancer, to avoid selection bias resulting from endoscopy.
H. pylori status of 86 asymptomatic children was assessed by (13) C-urea breath test (UBT) and PCR. H. pylori 16S rRNA, cagA, hopQ, and vacA genes were amplified from stool DNA samples and sequenced.
UBT was positive in 69 (80.2%) of 86 children; in stool DNA analysis, 78.3% were positive by 16S rRNA PCR. cagA, vacA, and hopQ were detected in 66.1%, 84.6%, and 72.3% of stool DNA samples from 16S rRNA-positive children. Of the children's DNA samples, which revealed vacA and hopQ alleles, 91.7% showed vacA s1 and 73.7% showed type I hopQ. Type I hopQ alleles were associated with cagA positivity and vacA s1 genotypes (p < 0.0001).
Using stool DNA samples, virulence markers of H. pylori were successfully genotyped in a high percentage of the asymptomatic infected children, revealing a high prevalence of genotypes associated with virulence. Type I hopQ alleles were associated with the presence of cagA and the vacA s1 genotype.
[Show abstract][Hide abstract] ABSTRACT: Background and Objective: Because capsule endoscopy (CE) avoids ionizing radiation, deep sedation, and general anesthesia, CE may be valuable in pediatrics. We report a single pediatric center's experience with the use and safety of CE.
Methods: In a retrospective review of consecutive CE studies, 284 CE studies were performed in 277 patients with a mean age of 15 (±3.7) years during a 5-year period. The youngest to swallow the capsule was 4.6 years old. Twenty capsules were placed. Overall, 245 (86%) patients underwent CE for suspected (184, 65%) or confirmed (61, 21%) Crohn disease (CD); 27 (9.5%) anemia or gastrointestinal bleeding; 6 (2%) polyposis; and 4 (1.4%) celiac disease.
Results: Positive findings were observed in 205 (72%) of the studies, with 152 (54%) having small bowel findings. Of these, 72 (47%) were diagnostic. Gastric (95, 33%) and colonic (31, 11%) abnormalities were also identified. Five CE studies (1.8%) resulted in retention of the capsule in nonsurgical patients. A patency capsule before CE in 23 patients allowed 19 CE to proceed with only 1 retained capsule. In 65 (21%) patients, the video capsule did not enter the colon before the video's end. Of these, 36 (65%) had significant findings, including 27 (49%) documenting small bowel (SB) CD.
Conclusions: CE is useful to diagnose SB disease in children. Even in a study population with a high prevalence of confirmed and suspected CD, the risk of retention remains small. The patency capsule may lessen that risk. CE may identify gastric or colonic disease even when SB lesions are not present.
Journal of Pediatric Gastroenterology and Nutrition 02/2012; 54(3):409–413. · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As the clinical implications of Helicobacter pylori infection in children and adolescents continue to evolve, ESPGHAN and NASPGHAN jointly renewed clinical guidelines using a standardized evidence-based approach to develop updated recommendations for children and adolescents in North America and Europe.
An international panel of 11 pediatric gastroenterologists, 2 epidemiologists, 1 microbiologist, and 1 pathologist was selected by societies that developed evidence-based guidelines based on the Delphi process with anonymous voting in a final face-to-face meeting. A systematic literature search was performed on 8 databases of relevance including publications from January 2000 to December 2009. After excluding nonrelevant publications, tables of evidence were constructed for different focus areas according to the Oxford classification. Statements and recommendations were formulated in the following areas: whom to test, how to test, whom to treat, and how to treat. Grades of evidence were assigned to each recommendation based on the GRADE system.
A total of 2290 publications were identified, from which 738 were finally reviewed. A total of 21 recommendations were generated, and an algorithm was proposed by the joint committee providing evidence-based guidelines on the diagnostic workup and treatment of children with H pylori infection.
These clinical practice guidelines represent updated, best-available evidence and are meant for children and adolescents living in Europe and North America, but they may not apply to those living on other continents, particularly in developing countries with a high H pylori infection rate and limited health care resources.
Journal of pediatric gastroenterology and nutrition 05/2011; 53(2):230-43. · 2.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The current study involved the development and evaluation of a skills-based, psychological intervention for adolescent females with inflammatory bowel disease (IBD) and their parents. Psychological interventions were used to improve coping with pain and other somatic physical symptoms, as well as improve parental responses to children and adolescents who experience such symptomatology.
Thirteen and 11 adolescent females and one of their parents made up the treatment and wait-list control groups, respectively, for a total of 24 parent-child dyads. Adolescents and parents attended a 1-day intervention that taught disease-related coping skills, pain management, relaxation techniques, communication, and limit setting (parents only). The treatment day was followed by 6 weeks of Web-based skill review including homework assignments and weekly group chat sessions.
Following treatment, significant improvements were found in adolescents' somatic symptoms and adaptive coping strategies. Further, parents reported reductions in irrational thoughts and improved behavioral reactions related to their daughter's physical symptoms. Implications of these findings, as well as limitations and future directions, are discussed.
Overall, preliminary support suggests that programmatic psychosocial interventions for reducing physical symptoms and improving coping may be beneficial for adolescents with IBD and their families.
[Show abstract][Hide abstract] ABSTRACT: The goal was to compare the frequency of children's antibiotic intake, emphasizing antibiotics with anti-Helicobacter pylori effects, in El Paso, Texas, and Juarez, Mexico.
Hispanic children were enrolled prenatally at mother-child clinics in El Paso, and Juarez, in 1998-2000, to identify determinants of H pylori infection. During follow-up examinations targeted every 6 months from 6 to 84 months of age, caretakers reported medication use during the preceding interval. Courses of any systemic and H pylori-effective antibiotics were compared for US and Mexican children.
Antibiotic data were available for 602 children, from 2938 follow-up visits. Overall antibiotic intake was higher in Juarez, where 84% of children received > or = 1 course during the follow-up period (52% of visits), compared with El Paso, where 76% of children received > or = 1 course (40% of visits). In contrast, the intake of H pylori-effective antibiotics was higher in El Paso, where 65% of children received > or = 1 course during the follow-up period (27% of visits), compared with Juarez, where 44% of children received > or = 1 course (16% of visits). Of H pylori-effective courses, 94% contained amoxicillin and 2% each clarithromycin, metronidazole, and furazolidone; uses were primarily for throat and ear infections, diarrhea, and cold/flu.
Pediatric antibiotic use was higher in Mexico than on the US side of the border. Apparent misuse of H pylori-effective antibiotics was more frequent in Juarez but also occurred in El Paso. Such misuse of antibiotics may lead to drug resistance and may impair the control of H pylori infection in this region.
[Show abstract][Hide abstract] ABSTRACT: This pilot study in parenteral nutrition-dependent infants with short bowel syndrome (SBS) evaluated the impact of feeding route and intestinal permeability on bloodstream infection (BSI), small bowel bacterial overgrowth (SBBO), and systemic immune responses, as well as fecal calprotectin as a biomarker for SBBO.
Ten infants (ages 4.2-15.4 months) with SBS caused by necrotizing enterocolitis were evaluated. Nutritional assessment, breath hydrogen testing, intestinal permeability, fecal calprotectin, serum flagellin- and lipopolysaccharide-specific antibody titers, and proinflammatory cytokine concentrations (tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta, -6, and -8) were performed at baseline and at 60 and 120 days. Healthy, age-matched control subjects (n = 5) were recruited.
BSI incidence was high (80%), and SBBO was common (50%). SBBO increased the odds for BSI (>7-fold; P = .009). Calprotectin levels were higher in children with SBS and SBBO versus those without SBBO and healthy control subjects (P < .05). Serum TNF-alpha, was elevated at baseline versus controls. Serum TNF-alpha and interleukin-1 beta, -6, and -8 levels diminished with increased enteral nutrition. Anti-flagellin and anti-lipopolysaccharide immunoglobulin G levels in children with SBS were lower versus control subjects and rose over time.
In children with SBS, SBBO increases the risk for BSI, and systemic proinflammatory response decreases with increasing enteral feeding and weaning parenteral nutrition.
The Journal of pediatrics 02/2010; 156(6):941-7, 947.e1. · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ZielEs sollte ein internationaler Konsensus zur Definition der gastroösophagealen Refluxkrankheit (GÖRK) in der Pädiatrie erzielt
MethodenNach systematischer Literatursuche wurden von einer internationalen Gruppe von Kindergastroenterologen Kernaussagen entwickelt
und anonym in einem modifizierten Delphi-Verfahren abgestimmt. Die Evidenzstärke orientierte sich am GRADE-System (Grading
of Recommendations, Assessment, Development and Evaluation).
ErgebnisseKonsens wurde bei 98% der 59Kernaussagen erreicht. Wichtige Punkte sind: 1) GÖRK liegt vor, wenn Reflux von Mageninhalt belastende
Symptome (Beschwerden) oder Komplikationen verursacht. Die Definition ist bei Kindern unter etwa 8Jahren eingeschränkt, da
diese nicht zuverlässig belastende Symptome angeben können. 2) Histologie dient v.a. zum Ausschluss anderer Ösophaguserkrankungen,
weniger zur Sicherung der Diagnose GÖRK. 3) Barrett-Ösophagus beschreibt eine Schleimhautmetaplasie in der Speiseröhre, die
positiv oder negativ für Becherzellen sein kann. 4) Extraösophageale Erkrankungen können mit GÖRK assoziiert sein, eine Kausalität
ist für die meisten nicht gesichert.
ZusammenfassungDas Konsensuspapier wurde unter strikten Kriterien entwickelt und kann die Basis für klinische Studien und Leitlinien bilden.
ObjectiveAn international consensus on the definition of gastroesophageal reflux disease (GERD) in pediatrics was sought.
MethodsAfter a systematic literature search, a set of key statements was developed by an international panel of pediatric gastroenterologists
and voted anonymously in a modified Delphi process. The strength of each statement was assessed using the GRADE system.
ResultsConsensus was reached on 98% of the 59 statements. Consensus items of particular note were: (1) GERD is present when reflux
of gastric contents causes troublesome symptoms and/or complications. The definition is restricted in the case of children
under ~8years, due to unreliable reporting of incriminating symptoms; (2) the primary role of histology is to exclude other
conditions, rather than to establish the diagnosis of GERD; (3) Barrett’s esophagus characterizes an esophageal metaplasia
that is intestinal metaplasia-positive or -negative; (4) extraesophageal conditions may be associated with GERD, but for most
of these conditions causality remains to be established.
ConclusionsThe consensus statements were developed by means of a rigorous process and can form the basis for clinical trials and practice
[Show abstract][Hide abstract] ABSTRACT: Although gastroesophageal reflux disease (GERD) is common in adolescents, the burden of GERD on health-related quality of life (HRQOL) in adolescents has not been previously evaluated. Therefore, the objective of the study was to examine the effect of GERD on HRQOL in adolescents.
This international, 31-site, 8-week safety study randomized adolescents, aged 12 to 17 years inclusive, with GERD to receive esomeprazole 20 or 40 mg once daily. The Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD), previously validated in adults, consists of 25 questions grouped into 5 domains: emotional distress, sleep disturbance, food/drink problems, physical/social functioning, and vitality. The QOLRAD was administered at the baseline and week-8 (final) visits.
Of the 149 patients randomized, 134 completed the QOLRAD at baseline and final visits and were eligible for analysis of their HRQOL data. Baseline QOLRAD scores indicated GERD had a negative effect on the HRQOL of these adolescents, especially in the domains of vitality and emotional distress, and problems with food/drink. At the final visit, mean scores for all 5 QOLRAD domains improved significantly (P < .0001); change of scores (ie, delta) for all domains met or exceeded the adult QOLRAD minimal clinically significant difference standard of 0.5 units.
GERD had a negative effect on QOL in adolescents. After esomeprazole treatment, statistically and clinically significant improvements occurred in all domains of the QOLRAD for these adolescents.
D9614C00098; ClinicalTrials.gov Identifier NCT00241501.
[Show abstract][Hide abstract] ABSTRACT: The development of disease complications is poorly characterized in pediatric patients with Crohn's disease (CD).
We retrospectively determined the cumulative incidence of stricturing and penetrating complications of CD prior to first surgery utilizing data from 989 consecutively enrolled CD patients (age 0-17 years at diagnosis) collected between January 2000 and November 2003 and stored in the Pediatric IBD Consortium Registry.
Mean age at diagnosis was 11.5 +/- 3.8 (standard deviation) years. Median follow-up time was 2.8 years. Prior to first surgery, the cumulative incidence of stricturing or penetrating complications was 27% at 5 years and 38% at 10 years from the diagnosis of inflammatory bowel disease. The cumulative incidence of complicated disease was lowest in isolated colonic disease (P = 0.009). Penetrating complications that followed stricturing complications prior to first surgery occurred within 2 years of stricturing complications (cumulative incidence was 13% at 2 years from diagnosis of stricturing disease). Stricturing complications that followed penetrating complications prior to first surgery occurred within 8 years of penetrating complications (cumulative incidence was 26% at 8 years from diagnosis of penetrating complications).
Strictures, abscesses, and fistulas are common in pediatric CD. Earlier aggressive management may be indicated. Prospective study is required to identify genetic and serologic markers that predict a patient's risk for the development of complicated disease and to determine optimal treatment regimens.
[Show abstract][Hide abstract] ABSTRACT: To develop an international consensus on the definition of gastroesophageal reflux disease (GERD) in the pediatric population.
Using the Delphi process, a set of statements was developed and voted on by an international panel of eight pediatric gastroenterologists. Statements were based on systematic literature searches using Medline, EMBASE, and CINAHL. Voting was conducted using a six-point scale, with consensus defined, a priori, as agreed by 75% of the group. The strength of each statement was assessed using the GRADE system.
There were four rounds of voting. In the final vote, consensus was reached on 98% of the 59 statements. In this vote, 95% of the statements were accepted by seven of eight voters. Consensus items of particular note were: (i) GERD is present when reflux of gastric contents causes troublesome symptoms and/or complications, but this definition is complicated by unreliable reporting of symptoms in children under the age of approximately 8 years; (ii) histology has limited use in establishing or excluding a diagnosis of GERD; its primary role is to exclude other conditions; (iii) Barrett's esophagus should be defined as esophageal metaplasia that is intestinal metaplasia positive or negative; and (iv) extraesophageal conditions may be associated with GERD, but for most of these conditions causality remains to be established.
The consensus statements that comprise the Definition of GERD in the Pediatric Population were developed through a rigorous process. These statements are intended to be used for the development of future clinical practice guidelines and as a basis for clinical trials.
The American Journal of Gastroenterology 05/2009; 104(5):1278-95; quiz 1296. · 9.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Helicobacter pylori strains display remarkable genetic diversity, and the presence of strains bearing the toxigenic vacA s1 allele, a complete cag pathogenicity island (PAI), cagA alleles containing multiple EPIYA phosphorylation sites, and expressing the BabA adhesin correlates with development of gastroduodenal disease in adults. To better understand the genetic variability present among pediatric strains and its relationship to disease, we characterized H. pylori strains infecting 47 pediatric North American patients. Prevalence of mixed infection was assessed by random amplified polymorphic DNA analysis of multiple H. pylori clones from each patient. Microarray-based comparative genomic hybridization was used to examine the genomic content of the pediatric strains. The cagA and vacA alleles were further characterized by allele-specific PCR. A range of EPIYA motif configurations were observed for the cagA gene, which was present in strains from 22 patients (47%), but only 19 (41%) patients contained a complete cag PAI. Thirty patients (64%) were infected with a strain having the vacA s1 allele, and 28 patients (60%) had the babA gene. The presence of a functional cag PAI was correlated with ulcer disease (P = 0.0095). In spite of declining rates of H. pylori infection in North America, at least 11% of patients had mixed infection. Pediatric strains differ in their spectrum of strain-variable genes and percentage of absent genes in comparison to adult strains. Most children were infected with H. pylori strains lacking the cag PAI, but the presence of a complete cag PAI, in contrast to other virulence markers, was associated with more severe gastroduodenal disease.
Journal of clinical microbiology 05/2009; 47(6):1680-8. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Folate is postulated to protect against cell injury and long-term risk of cancer. Folate deficiency has been shown to be associated with inflammatory bowel disease (IBD). However, folate concentrations are poorly delineated in children with IBD.
The objective was to compare folate concentrations between children with newly diagnosed IBD and healthy controls.
Red blood cell folate (RBCF) and whole-blood folate (WBF) concentrations were measured in 78 children (mean age: 12.8 +/- 2.7 y): 22 patients with newly diagnosed untreated Crohn disease, 11 patients with ulcerative colitis, 4 patients with indeterminate colitis, and 41 controls. Vitamin supplementation and dietary intakes determined by food-frequency questionnaire were recorded for 20 IBD patients and 28 controls.
RBCF concentrations were 19.4% lower in controls (587.0 +/- 148.6 ng/mL) than in patients (728.7 +/- 185.8 ng/mL; P = 0.0004), and WBF concentrations were 11.1% lower in controls (218.2 +/- 49.7 ng/mL) than in patients (245.3 +/- 59.1 ng/mL; P = 0.031). Total folate intake was 18.8% higher in controls (444.7 +/- 266.7 microg/d) than in IBD patients (361.1 +/- 230.6 microg/d), but this difference was not statistically significant (P = 0.264). Folate intakes were below the Recommended Dietary Allowance (200-400 microg/d), adjusted for age and sex, in 35.4% of study subjects.
In contrast with previous evidence of folate deficiency in adult IBD patients, our data indicate higher folate concentrations in children with newly diagnosed untreated IBD than in controls. This finding was unexpected, especially in light of the higher dietary folate intakes and hematocrit values in children without IBD. The influence of IBD therapy on folate metabolism and the long-term clinical implications of high RBCF and WBF concentrations at the time of IBD diagnosis should be explored further.
American Journal of Clinical Nutrition 01/2009; 89(2):545-50. · 6.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the current study was to determine whether age and body satisfaction predict dietary adherence in adolescents with Inflammatory Bowel Disease (IBD), and whether older females are less adherent than younger males and females. Forty-four participants aged 10-21 with IBD were recruited. Participants provided informed consent and demographics. Body satisfaction was measured by a questionnaire and a task in which participants selected their current and ideal body image out of silhouettes depicting bodies ranging from underweight to obese. Adherence was measured by marking a 100 mm visual analog scale, the 1-week completion of a dietary log, and a questionnaire evaluating coping strategies used for overcoming obstacles to dietary adherence. Age was related to dietary adherence, with younger children being more likely to adhere. Participants more satisfied with their body reported better dietary adherence. Findings remained consistent across multiple measures of body satisfaction and adherence. Healthcare providers and parents should be informed of these findings in order to improve adherence.
Journal of Clinical Psychology in Medical Settings 01/2009; 15(4):278-86. · 1.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The relationship between the age at diagnosis and disease course is poorly defined in children with Crohn's disease (CD). We examined the presentation and course of disease in patients 0-5 compared to 6-17 yr of age at diagnosis.
We analyzed uniform data from 989 consecutive CD patients collected between January 2000 and November 2003, and stored in the Pediatric IBD Consortium Registry. The statistical tests account for the length of follow-up of each patient.
In total, 98 patients (9.9%) were of 0-5 yr of age at diagnosis. The mean follow-up time was 5.6 +/- 5.0 yr in the younger group and 3.3 +/- 2.8 yr in the older group (P < 0.001). Race/ethnicity differed by the age group (P= 0.015); a larger proportion of the younger group was Asian/Pacific Islander or Hispanic, and a larger proportion of the older group was African American. The initial classification as ulcerative colitis or indeterminate colitis was more common among the 0-5 yr of age group (P < 0.001). The 6-17 yr of age patients presented with more abdominal pain (P < 0.001), weight loss (P= 0.001), or fever (P= 0.07), while the 0-5 yr of age patients presented with more rectal bleeding (P= 0.008). The 6-17 yr of age patients were more likely to be treated with antibiotics (P < 0.001), 6-mercaptopurine/azathioprine (P < 0.001), infliximab (P= 0.001), or corticosteroids (P= 0.0006). The 6-17 yr of age patients had a higher cumulative incidence of treatment with 5-aminosalicylates (P= 0.009) or methotrexate (P= 0.04). The risk for developing an abscess (P= 0.001), a fistula (P= 0.02), a stricture (P= 0.05), or a perianal fissure (P= 0.06) was greater in the 6-17 yr of age patients.
The 6-17 yr of age patients with CD appear to have a more complicated disease course compared to 0-5 yr of age children. The 0-5 yr of age group may represent a unique disease phenotype and benefit from different approaches to management. Long-term prospective studies are required to validate these findings.
The American Journal of Gastroenterology 09/2008; 103(8):2092-8. · 9.21 Impact Factor