Molly O'Gorman

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.

Impact of fundoplication versus gastrojejunal feeding tubes on mortality and in preventing aspiration pneumonia in young children with neurologic impairment who have gastroesophageal reflux disease.

OBJECTIVE. Aspiration pneumonia is the most common cause of death in children with neurologic impairment who have gastroesophageal reflux disease. Fundoplications and gastrojejunal feeding tubes are frequently employed to prevent aspiration pneumonia in this population. Which of these approaches is more effective in preventing aspiration pneumonia and/or improving survival is unknown. The objective of this study was to compare outcomes for children with neurologic impairment and gastroesophageal reflux disease after either a first fundoplication or a first gastrojejunal feeding tube. PATIENTS AND METHODS. This was a retrospective, observational cohort study of children with neurologic impairment who had either a fundoplication or gastrojejunal feeding tube between January 1997 and December 2005 at a tertiary care childrens hospital. Main outcome measures were postprocedure aspiration pneumonia–free survival and mortality. Propensity analyses were used to control for bias in treatment assignment and prognostic imbalances. RESULTS. Of the 366 children with neurologic impairment and gastroesophageal reflux disease, 43 had a first gastrojejunal feeding tube and 323 underwent a first fundoplication. Median length of follow-up was 3.4 years. Children who received a first fundoplication had similar rates of aspiration pneumonia and mortality after the procedure compared with those who had a first gastrojejunal feeding tube, when adjusting for the treatment assignment using propensity scores. CONCLUSIONS. Aspiration pneumonia and mortality are not uncommon events after either a first fundoplication or a first gastrojejunal feeding tube for the management of gastroesophageal reflux disease in children with neurologic impairment. Neither treatment option is clearly superior in preventing the subsequent aspiration pneumonia or improving overall survival for these children. This complex clinical scenario needs to be studied in a prospective, multicenter, randomized control trial to evaluate definitively whether 1 of these 2 management options is more beneficial.

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. (Inflamm Bowel Dis 2011;)

Effect of gastrojejunal feedings on visits and costs in children with neurologic impairment

Objective: The objective of the present study was to determine the effect of gastrojejunal tube (GJT) feedings in children with neurologic impairment (NI) on gastroesophageal reflux disease (GERD)– and/or dysfunctional swallowing–related visits and their associated costs. Methods: The present study is a retrospective cohort study of children with NI and GERD who underwent GJT placement at the study hospital from December 1999 to October 2006. Visits (emergency department, radiology, and hospitalizations) were reviewed from the time of birth until 1 year following GJT placement and classified as either not GERD and/or dysfunctional swallowing related or GERD and/or dysfunctional swallowing related (eg, pneumonias). Incident rate ratios (IRRs) were calculated by dividing the post-GJT visit rate by the pre-GJT visit rate. Other outcomes included associated costs, fundoplications, and deaths. Results: Thirty-three patients met inclusion criteria. The IRR for total visits was 1.78 (95% confidence interval [CI] 1.12–2.81) and for GERD- and/or dysfunctional swallowing–related visits 2.88 (95% CI 1.68–4.94). Feeding tube-related visits (IRR 5.36, 95% CI 2.73–10.51) accounted for the majority. GERD- and/or dysfunctional swallowing–related costs per child per year were low overall, with no difference from pre-GJT versus post-GJT placement (

Natural Killer Cell Lymphoma in a Pediatric Patient With Inflammatory Bowel Disease

1851 vs

High-Dose Steroids, Ursodeoxycholic Acid, and Chronic Intravenous Antibiotics Improve Bile Flow After Kasai Procedure in Infants With Biliary Atresia

4601, P = 0.89). Seven (21%) children underwent Nissen fundoplication and 4 (12%) died within 1 year of GJT placement. Two deaths involved jejunal perforation. Conclusions: Children with NI and GERD who are treated with GJT feedings have significantly more GERD- and/or dysfunctional swallowing–related visits in the following year. The majority of these visits are because of the procedural complications, which are inexpensive. There is, however, mortality associated with the GJT and some children proceed to a fundoplication.

Quality of life of children with neurological impairment who receive a fundoplication for gastroesophageal reflux disease

Tumor necrosis factor α (TNF-α) antibody agents are an effective therapy for the treatment of inflammatory bowel disease (IBD); however, because of the potential for immune suppression with these drugs, TNF-α antibody agents can increase the risk of malignancy. We report here the case of an 11-year-old boy who presented with bowel obstruction. He also had a history of periodic fever, aphthous stomatitis, and cervical adenitis (PFAPA). Intestinal inflammation continued and impaired his quality of life; he was diagnosed with IBD of an undetermined type (IBD-U). Symptoms improved with infliximab, but he developed elevated transaminase levels with hepatosplenomegaly 1 year after scheduled infusions. Skin biopsy revealed an atypical lymphoid infiltrate consistent with an Epstein-Barr virus (EBV)-positive natural killer (NK)/T-cell lymphoma with associated hemophagocytic lymphohistiocytosis. Bone marrow biopsy revealed a similar EBV-positive lymphoid infiltrate consistent with an NK/T-cell lymphoma. EBV-positive tissue was present in gastrointestinal biopsies. Flow-cytometric analysis revealed an atypical, clonal NK-cell population, and biopsy specimens from several tissue sites tested positive for CD3, CD56, and CD30. The patient died soon after the diagnosis was made. This patient developed an EBV-driven malignancy while receiving infliximab. All patients with IBD who receive infliximab should be monitored for malignancy, especially young patients. This case underscores the need for future studies to better understand the biology of lymphoproliferative disorders.