Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis.

BACKGROUND & AIMS: We evaluated the efficacy and safety of high-dose swallowed fluticasone propionate (FP) and dose reduction in patients with eosinophilic esophagitis (EoE) and analyzed esophageal transcriptomes to identify mechanisms. METHODS: We conducted a randomized, multisite, double-blind, placebo-controlled trial of daily 1760 mcg FP in participants age 3-30 years with active EoE. Twenty-eight participants received FP, and 14 participants received placebo. After 3 months, participants given FP who were in complete remission (CR) received 880 mcg FP daily, and participants in the FP or placebo groups who were not in CR continued or started, respectively, 1760 mcg FP daily for 3 additional months. The primary end point was histologic evidence for CR. Secondary end points were partial remission (PR), symptoms, compliance, esophageal gene expression, esophageal eosinophil count, and the relationship between clinical features and FP responsiveness. RESULTS: After 3 months, 65% of subjects given FP and no subjects given placebo were in CR (P = .0001); 12% of those given FP and 8% of those given placebo were in PR. In the FP group, 73% of subjects remained in CR, and 20% were in PR after the daily dose was reduced by 50%. Extending FP therapy in FP-resistant participants did not induce remission. FP decreased heartburn severity (P = .041). Compliance, age, sex, atopic status, or anthropomorphic features were not associated with response to FP. Gene expression patterns in esophageal tissues of FP responders were similar to those of patients without EoE; there was evidence for heterogeneous steroid signaling in subjects who did not respond to FP and preliminary evidence for transcripts predictive of FP responsiveness. CONCLUSIONS: Daily administration of a high dose of FP induces histologic remission in 65%-77% of patients with EoE after 3 months. A 50% dose reduction remained effective in 73%-93% of patients who initially responded to FP. Nonresponders had evidence of steroid resistance; histologic and molecular markers may predict resistance. Clinicaltrials.gov number: NCT00426283.

Foreign body impaction as presentation of eosinophilic esophagitis.

Esophageal foreign body is a frequent pediatric presentation, and eosinophilic esophagitis (EoE) is an important underlying disease. To determine characteristics common in the presentation of esophageal foreign body indicative of underlying EoE and reach a recommendation for the appropriate scenario in which to obtain esophageal mucosal biopsy, 312 pediatric esophageal foreign bodies requiring operative removal were reviewed. Patients older than 18 years or with a known history of esophageal surgery or pathology were excluded. Eligibility criteria were met in 271 cases. Twenty-seven patients were biopsied, and 18 were diagnosed with EoE. The following factors were identified in the EoE population: food impaction (89%), older age (average 12.2 years), male sex (78%), atopic disease (61%), previous esophageal foreign body or frequent dysphagia (83%), and endoscopic abnormalities (100%). These factors are all associated with an underlying diagnosis of EoE, and patients meeting these criteria should be strongly considered for intraoperative esophageal mucosal biopsy.

Effect of decreased parenteral soybean lipid emulsion on hepatic function in infants at risk for parenteral nutrition-associated liver disease: a pilot study.

PURPOSE: We performed a pilot trial to compare reduced dose versus standard soybean lipid emulsion in neonates at risk for parenteral nutrition-associated liver disease. METHODS: A prospective randomized controlled trial was performed (2009-2011) enrolling surgical patients ≥ 26 weeks' gestation anticipated to require >50% of daily caloric intake from parenteral nutrition (PN) for at least 4 weeks. Randomization occurred into either reduced (1.0 g/kg/day) or standard (3g/kg/day) groups. Co-primary outcomes for interpretation of the results were conjugated bilirubin and total bile acids. Additional outcomes included ALT, AST, GGT, alkaline phosphatase, growth, and essential fatty acid levels. Outcomes were compared between treatment groups using Wilcoxon rank sums tests. RESULTS: Twenty-eight patients (47% enrollment rate) were included in the study with an average treatment duration of 5.4 weeks. Groups had similar PN calories and protein intake throughout the study. Total increase from baseline was smaller in the reduced vs. standard group for conjugated bilirubin (p=0.04) and total bile acids (p=0.02). Weight z-score increased more in the standard group, and no patient experienced essential fatty acid deficiency. CONCLUSION: Markers of cholestasis rose at a slower rate using reduced lipid doses. This pilot study demonstrates feasibility and need for a larger study evaluating the effects of reduced lipids in patients at risk for developing parenteral nutrition-associated liver disease.

Adverse outcomes associated with gastroesophageal reflux disease are rare following an apparent life-threatening event.

OBJECTIVE: To evaluate for adverse outcomes associated with gastroesophageal reflux disease (GERD) following an apparent life-threatening event (ALTE) and potential risk factors of these outcomes. STUDY DESIGN: Retrospective cohort study of well-appearing infants (<12 months) admitted for ALTE. Patients were followed for adverse outcomes associated with GERD (including aspiration pneumonia, failure-to-thrive, or anti-reflux surgery), second ALTE, or death. Risk factors evaluated included: age, prematurity, gender, previous event, diagnosis of GERD, gastrointestinal (GI) testing positive for gastroesophageal reflux, length of stay (LOS), and neurologic impairment diagnosed in follow-up. RESULTS: Four hundred sixty-nine patients met inclusion criteria, mean age was 45 days, 110 (22%) were premature. Patients were followed for an average of 7.8 years; 3.8% of all patients had an adverse outcome associated with GERD. The only significant risk factors were a longer LOS, and development of neurological impairment. A diagnosis of GERD and positive reflux testing during the initial hospitalization were not associated with adverse outcomes associated with GERD. CONCLUSIONS: Adverse outcomes associated with GERD are rare following an ALTE. Patients who developed neurological impairment and a longer initial LOS were at higher risk for developing these outcomes. Positive testing for gastroesophageal reflux during hospitalization for ALTE did not predict adverse outcomes associated with GERD.

Clinical variables as prognostic tools in pediatric-onset ulcerative colitis: a retrospective cohort study.

BACKGROUND: Clinical variables may identify a subset of patients with pediatric-onset ulcerative colitis (UC) (≤18 years at diagnosis) at risk for adverse outcomes. We postulated that routinely measured clinical variables measured at diagnosis would predict colectomy in patients with pediatric-onset UC. METHODS: We conducted a chart review of patients with pediatric-onset UC at a single center over a 10-year period. We compared patients with and without colectomy across several variables, used proportional hazards regression to adjust for potential confounders, and assessed the ability of a UC risk score to predict colectomy. RESULTS: Among 470 patients with inflammatory bowel disease ICD9-coded encounters, 155 patients had UC and 135 were eligible for analysis. The 1- and 3-year colectomy rates were 16.7% (95% confidence interval [CI]: 11.0%-24.8%) and 35.6% (26.7%-45.4%). White blood cell (WBC) count and hematocrit measured at diagnosis were associated with colectomy at 3 years, even after correcting for potential confounding variables. A UC Risk Score derived from the WBC count and hematocrit was strongly associated with colectomy risk, with a high negative predictive value (NPV) for colectomy at 1 and 3 years (NPV = 0.95 and 0.89, respectively), but low positive predictive value (PPV = 0.22 and 0.38, respectively). CONCLUSIONS: A risk score calculated from WBC and hematocrit measured at diagnosis was associated with, but incompletely predictive of, colectomy in pediatric-onset UC. These data suggest 1) routinely measured clinical variables may have a prognostic role in risk stratification, and 2) multicenter prospective studies are needed to optimize risk stratification in pediatric UC. Our findings have impact on the design of such studies.

Improving the prevention, early recognition, and treatment of pediatric obesity by primary care physicians.

To determine if participation in a learning collaborative (LC) would improve care processes for prevention, early recognition, and treatment of childhood obesity by primary care physicians (PCP), the authors conducted pre-post evaluations of the use of obesity related care processes by 18 primary care practices following participation in a 9-month LC based on the Model for Improvement. Prior to the LC, chart audits revealed that 55% of patients had a BMI recorded; this rose to 97% of patients at its conclusion. Following the LC, 11 practices had implemented systematic prevention advice to parents of infants compared with 3 prior to the LC. All practices developed plans for evaluation and management of children with an elevated BMI. Participation in an LC increased the number of primary care practices that provided anticipatory guidance regarding obesity prevention and that identified and treated overweight or obese children.

Elimination of soybean lipid emulsion in parenteral nutrition and supplementation with enteral fish oil improve cholestasis in infants with short bowel syndrome.

BACKGROUND: Parenteral nutrition-associated liver disease (PNALD) is a potentially fatal complication for children with intestinal failure. Fish oil-based lipid emulsions have shown promise for the treatment of PNALD but are not readily available. Six cases are presented in which cholestasis resolved after soybean lipid emulsion (SLE) was removed from parenteral nutrition (PN) and enteral fish oil was given. METHODS: A retrospective review at a tertiary children's hospital (July 2003 to August 2008) identified 6 infants with intestinal failure requiring PN for >6 months who developed severe hepatic dysfunction that was managed by eliminating SLE and providing enteral fish oil. RESULTS: Twenty-three infants with short bowel syndrome requiring prolonged PN developed cholestasis. SLE was removed in 6 of these patients, and 4 of the 6 received enteral fish oil. Standard PN included 2-3 g/kg/d SLE with total PN calories ranging from 57 to 81 kcal/kg/d at the time of SLE removal. Hyperbilirubinemia resolved after elimination of SLE within 1.8-5.4 months. Total PN calories required to maintain growth generally did not change. CONCLUSIONS: Temporary elimination of SLE and supplementation with enteral fish oil improved cholestasis in PN-dependent infants. Further trials are needed to evaluate this management strategy.

Correlation of cholestasis with serum copper and whole-blood manganese levels in pediatric patients.

Many institutions reduce or eliminate copper (Cu) and manganese (Mn) in parenteral nutrition (PN) solutions when cholestasis develops. Little data exist to support this practice. Fifty-four subjects with known serum Cu, whole-blood Mn, and serum-conjugated bilirubin levels were evaluated in this prospective, observational study. Subjects ranged in weight from 760 g to 65.2 kg. Subjects weighing <25 kg received a daily parenteral dose of 20 microg/kg Cu and 5 microg/kg Mn. Subjects weighing > or =25 kg received a dose of 500 microg/d Cu and 150 microg/d Mn. Cholestasis was defined as a conjugated bilirubin level > or =2 mg/dL. Of the 54 subjects, 20 had cholestasis. Fifteen patients had elevated Cu levels, and 21 had high Mn levels. Seven of the subjects had both high Cu and high Mn levels. The regression model comparing cholestasis as a predictor of high, low, or normal Cu level was not significant (P = .9588). Cholestasis was not a significant predictor of high, low, or normal Mn levels (P = .6533). No correlation between Cu and Mn levels was found. The authors found no significant relationship between conjugated serum bilirubin levels > or =2.0 mg/dL, serum Cu, and whole-blood Mn levels. They found insufficient evidence to support the practice of dosing Mn from a Cu level or vice versa. They recommend obtaining Cu and Mn levels on all pediatric patients who develop cholestasis prior to adjusting parenteral doses and at regular intervals for all long-term PN patients.

Correlation of duodenal histology with tissue transglutaminase and endomysial antibody levels in pediatric celiac disease.

BACKGROUND & AIMS: IgA antibodies against tissue transglutaminase (TTGA) and endomysium (EMA) are sensitive and specific markers for celiac disease (CD). Data correlating TTGA and EMA levels with degree of villous atrophy are limited. We compared duodenal histopathology in pediatric CD patients with TTGA and EMA serologies, symptoms, height, and weight. METHODS: We identified 117 pediatric patients retrospectively who had serologic testing for IgA TTGA and IgA EMA and duodenal biopsies graded by modified Marsh criteria as 0-3c. Data were analyzed with Spearman rank correlation and multinomial logistic regression. RESULTS: IgA TTGA (r = .704, P < .001) and IgA EMA (r = 0.740, P < .001) correlated with intestinal villous atrophy in pediatric CD patients by Spearman rank correlation. Similar correlations were found in a subset of 23 patients younger than 3 years of age. Multinomial logistic regression revealed increased probability of Marsh 3a or greater changes with increasing TTGA or EMA levels. Strongly positive antibody levels (TTGA >100 units or EMA titer >1:1280) were highly specific (>98%) for Marsh 3a or greater lesions. Among symptoms, abdominal distention and diarrhea were associated with abnormal histology. CONCLUSIONS: IgA TTGA and EMA levels correlate with duodenal villous atrophy in pediatric CD patients. IgA TTGA >100 or EMA >1:1280 were nearly always associated with CD histopathology. With further validation of this observation, strongly positive titers might be considered sufficient for diagnosis of pediatric patients at risk for CD. Symptoms, height, and weight are not reliable predictors of CD.

High-dose steroids, ursodeoxycholic acid, and chronic intravenous antibiotics improve bile flow after Kasai procedure in infants with biliary atresia.

BACKGROUND/PURPOSE: Early reports suggest that the use of steroids after Kasai portoenterostomy may improve bile flow and outcome in infants with biliary atresia. METHODS: Of 28 infants with biliary atresia, half received adjuvant high-dose steroids, and half received standard therapy. Infants in the steroid group (n = 14) received intravenous solumedrol (taper of 10, 8, 6, 5, 4, 3, 2 mg/kg/d), followed by 8 to 12 weeks of prednisone (2 mg/kg/d). The steroid protocol also included ursodeoxycholic acid indefinitely and intravenous antibiotics for 8 to 12 weeks followed by oral antibiotic prophylaxis. Infants in the standard therapy group (n = 14) received no steroids, occasional ursodeoxycholic acid, and perioperative intravenous antibiotics followed by oral antibiotic prophylaxis. The infants were not assigned randomly, but rather received standard therapy or adjuvant steroid therapy according to individual surgeon preference. RESULTS: Eleven of 14 (79%) in the steroid group and 3 of 14 (21%) in the standard therapy group had a conjugated bilirubin level less than 1.0 within 3 to 4 months of surgery (P <.001). Fewer patients in the steroid group (21% v 85%) required liver transplantation or died during the first year of life (P <.001). Infants in the steroid group did better despite the fact that this group included 5 infants with biliary atresia-polysplenia-heterotaxia syndrome, a subgroup that might have been expected to have a poor prognosis. Neither bile duct size nor liver histology was a reliable predictor of success or failure in either group. CONCLUSIONS: Adjuvant therapy using high-dose steroids, ursodeoxycholic acid, and intravenous antibiotics may accelerate the clearance of jaundice and decrease the need for early liver transplantation after Kasai portoenterostomy.

Prolongation of satiety after low versus moderately high glycemic index meals in obese adolescents.

BACKGROUND: One in 5 American children is overweight, despite a decrease in total fat consumption. This has sparked an interest in the carbohydrate composition of diets, including the glycemic index (GI). OBJECTIVE: To investigate whether a low-GI meal replacement (LMR) produced similar metabolic, hormonal, and satiety responses in overweight adolescents as a low-GI whole-food meal (LWM) when compared with a moderately high-GI meal replacement (HMR). METHODS: Randomized, crossover study comparing LMR, HMR, and LWM in 16 (8 male/8 female) adolescents during 3 separate 24-hour admissions. The meal replacements consisted of a shake and a nutrition bar. Identical test meals were provided at breakfast and lunch. Metabolic and hormonal indices were assessed between meals. Measures of participants' perceived satiety included hunger scales and ad libitum food intake. RESULTS: The incremental areas under the curve for glucose were 46% and 43% lower after the LMR and LWM, respectively, compared with the HMR. Insulin's incremental area under the curve was also significantly lower after both low GI test meals (LMR = 36%; LWM = 51%) compared with the HMR. Additional food was requested earlier after the HMR than the LMR (3.1 vs 3.9 hours, respectively), although voluntary energy intake did not differ. CONCLUSIONS: Differences in insulin response between the meal replacements occurred, and prolongation of satiety after the LMR, based on time to request additional food, was observed. We speculate that the prolonged satiety associated with low GI foods may prove an effective method for reducing caloric intake and achieving long-term weight control.

Gastrointestinal polyposis in childhood: clinicopathologic and genetic features.

Gastrointestinal polyps and certain extraintestinal lesions in children may herald a hereditary polyposis syndrome, with an increased risk of neoplasia and other health problems for both children and their relatives. The availability of molecular/genetic screening tests has increased early diagnosis of younger members of known polyposis families. This article reviews the gross and microscopic features of polyposis syndromes of childhood and summarizes the molecular/genetic advances in this field. Clinical management is also briefly discussed.