Azithromycin and metronidazole versus metronidazole-based therapy for the induction of remission in mild to moderate paediatric Crohn's disease : a randomised controlled trial.

OBJECTIVE: Crohn's disease (CD) pathogenesis associated with dysbiosis and presence of pathobionts in the lumen, intracellular compartments and epithelial biofilms. Azithromycin is active in all three compartments. Our goal was to evaluate if azithromycin-based therapy can improve response and induce remission compared with metronidazole alone in paediatric CD. DESIGN: This blinded randomised controlled trial allocated children 5-18 years with 1012.5 or remission using intention to treat analysis. RESULTS: 73 patients (mean age 13.8±3.1 years) were enrolled, 35 to group 1 and 38 to group 2. Response and remission rates at week 8 were identical 23/35 (66%) in group 1 and 17/38 (45%) and 15/38 (39%) in group 2 (P=0.07 and P=0.025, respectively). The needed to treat for remission was 3.7. Faecal calprotectin declined significantly in group 1 (P=0.003) but not in group 2 (p=0.33), and was lower at week 8 (P=0.052). Additional therapy was required in 6/35(17%) from group 1 versus 16/38(42%) in group 2 (P=0.027) by week 8. Among 12 failures in group 2, open-label azithromycin led to remission in 10/12 (83%). CONCLUSIONS: The combination of azithromycin and metronidazole failed to improve response but was superior for induction of remission and reduction in calprotectin. TRIAL REGISTRATION NUMBER: NCT01596894.

ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents.

BACKGROUND: The diagnosis of pediatric-onset inflammatory bowel disease (PIBD) can be challenging in choosing the most informative diagnostic tests and correctly classifying PIBD into its different subtypes. Recent advances in our understanding of the natural history and phenotype of PIBD, increasing availability of serological and fecal biomarkers, and the emergence of novel endoscopic and imaging technologies taken together have made the previous Porto criteria for the diagnosis of PIBD obsolete. METHODS: We aimed to revise the original Porto criteria using an evidence-based approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD. These revised criteria are based on the Paris classification of PIBD and the original Porto criteria while incorporating novel data, such as for serum and fecal biomarkers. A consensus of at least 80% of participants was achieved for all recommendations and the summary algorithm. RESULTS: The revised criteria depart from existing criteria by defining 2 categories of ulcerative colitis (UC, typical and atypical); atypical phenotypes of UC should be treated as UC. A novel approach based on multiple criteria for diagnosing IBD-unclassified (IBD-U) is proposed. Specifically, these revised criteria recommend upper gastrointestinal endoscopy and ileocolonscopy for all suspected patients with PIBD, with small bowel imaging (unless typical UC after endoscopy and histology) by magnetic resonance enterography or wireless capsule endoscopy. CONCLUSIONS: These revised Porto criteria for the diagnosis of PIBD have been developed to meet present challenges and developments in PIBD and provide up-to-date guidelines for the definition and diagnosis of the IBD spectrum.

Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis.

BACKGROUND & AIMS: We evaluated the efficacy and safety of infliximab for inducing and maintaining benefit in children with moderately to severely active ulcerative colitis (UC). METHODS: Patients (6-17 years old) who had active UC (Mayo scores of 6-12; endoscopic subscores ≥ 2) and had not responded to or tolerated conventional treatment were given 5 mg/kg infliximab at weeks 0, 2, and 6. The primary end point was response at week 8 (decreases in Mayo scores ≥ 30% and ≥ 3 points and decreases in rectal bleeding subscores of ≥ 1 or an absolute subscore of ≤ 1). At week 8, only responders were randomly assigned to groups given infliximab every 8 or 12 weeks (q8w or q12w) and followed through week 54. Maintenance end points included pediatric UC activity index scores <10 points, defined as remission. RESULTS: At week 8, infliximab induced a response in 73.3% of patients (44 of 60) (95% confidence interval, 62.1%-84.5%; a positive result was defined by 95% confidence interval lower limit >40%). Among responders, twice as many were in remission at week 54 after q8w (8 of 21, 38.1%) than q12w (4 of 22, 18.2%; P = .146) therapy. Assuming the q8w remission rate for responders, the overall remission rate at week 54 would be 28.6%. Serious adverse events and infusion reactions occurred in similar proportions in the q8w and q12w groups. No deaths, malignancies, opportunistic infections, tuberculosis, or delayed hypersensitivity reactions were reported. CONCLUSIONS: Infliximab was safe and effective, inducing a response at week 8 in 73.3% of pediatric patients with moderate to severely active UC who did not respond to conventional therapy. The overall remission rate at week 54 for all enrolled patients was 28.6%, assuming the more effective q8w remission rate.

Risk of infection and prevention in pediatric patients with IBD: ESPGHAN IBD Porto Group commentary.

Combined immunosuppression by immunomodulators and biological therapy has become standard in the medical management of moderate-to-severe inflammatory bowel disease (IBD) because of clearly demonstrated efficacy. Clinical studies, registries, and case reports warn of the increased risk of infections, particularly opportunistic infections; however, already in the steroid monotherapy era, patients are at risk because it is accepted that a patient should be considered immunosuppressed when receiving a daily dose of 20 mg of prednisone for 2 weeks. Prescriptions increasingly involve azathioprine, methotrexate, and various biological agents. The TREAT registry evaluated safety in >6000 adult patients, half of them treated with infliximab (IFX) for about 1.9 years. IFX-treated patients had an increased risk of infections and this was associated with disease severity and concomitant prednisone use. The REACH study, evaluating the efficacy of IFX in children with moderate-to-severe Crohn disease, refractory to immunomodulatory treatment, reports serious infections as the major adverse events and their frequency is higher with shorter treatment intervals. The combination of immunosuppressive medications is a risk factor for opportunistic infections. Exhaustive guidelines on prophylaxis, diagnosis, and management of opportunistic infections in adult patients with IBD have been published by a European Crohn's and Colitis Organization working group, including clear evidence-based statements. We have reviewed the literature on infections in pediatric IBD as well as the European Crohn's and Colitis Organization guidelines to present a commentary on infection prophylaxis for the pediatric age group.

Gastrointestinal manifestations of cow's milk protein allergy and gastrointestinal motility.

UNLABELLED: Cow's milk protein allergy (CMPA) may cause gastrointestinal motility disorders. Symptoms of both conditions overlap and diagnostic tests do not reliably differentiate between both. A decrease of symptoms with an extensive hydrolysate and relapse during challenge is not a proof of allergy, because hydrolysates enhance gastric emptying, a pathophysiologic mechanism of gastro-oesophageal reflux (GER). Thickened formula reduces regurgitation, and failure to do so suggests CMPA. A thickened extensive hydrolysate may induce more rapid improvement, but does not always differentiate between CMPA and GER. Different hypotheses are discussed: is the overlap between CMPA and functional disorders coincidence, or do both entities present with identical symptoms, or does the fact that symptoms are identical indicates that there is only one entity involved? Studies on the prevention of CMPA focused on 'at-risk families', and resulted in a decrease of CMPA and atopic dermatitis, but did not provide data on the incidence of GER. CONCLUSION: As long as there are no objective diagnostic tools to separate GER from CMPA, the physician has two options: first treat the most likely diagnosis, and switch if after 2-4 weeks there is no improvement, or treat both conditions with one intervention, what will not result in a diagnosis.

Treatment of infants and toddlers with cystic fibrosis-related pancreatic insufficiency and fat malabsorption with pancrelipase MT.

BACKGROUND: Pancreatic enzyme replacement therapy (PERT) improves nutritional status and growth in patients with cystic fibrosis (CF) with pancreatic insufficiency (PI). The current recommendation for infants and young children, who are not able to swallow the whole capsule, is to open the capsule and mix the beads in a spoon with some applesauce; however, the efficacy and safety data of this approach are currently lacking. The aim of this study was to assess the efficacy, palatability (ease of swallowing), and safety of 4 dose levels of pancrelipase microtablets (Pancrease MT) in infants and young children with CF-related PI. PATIENTS AND METHODS: This study was a phase II randomized, investigator-blinded, parallel-group pilot study in DNA-proven infants with CF and PI. The study design included a run-in period (days 1-5) and an experimental period (days 6-11). Pancrelipase microtablets (2-mm, enteric coated) were provided orally. Sixteen subjects, 6 to 30 months of age, were provided 500 U lipase/kg/meal for 5 days (baseline period). Subsequently, subjects were randomly assigned to 1 of 4 treatment groups (each n = 4), receiving 500, 1000, 1500, or 2000 U (Ph. EUR) of lipase/kg/meal, respectively, for 5 days (experimental period). The primary endpoint was medication efficacy assessed by the 72-hour fecal fat excretion, expressed as coefficient of fecal fat absorption (CFA), and 13C mixed triglyceride breath test. Secondary endpoints were safety and palatability. RESULTS: Overall compliance, defined as used study medication, was 89% to 99% for the entire study. None of the 4 dose regimens significantly influenced the CFA, relative to the baseline period (median range 83%-93%). During the run-in period the median cumulative % 13C was 11 (range -8 to 59). After randomization the median cumulative % 13C was 18 (range 14-23) in the 500-U, 14 (range -1 to 17) in the 1000-U, 10 (range 10-27) in the 1500-U, and 3 (range 1-49) in the 2000-U groups. Palatability was scored fair to good by the parents in each of the treatment groups. Gastrointestinal symptoms were reported in some patients, including common adverse events reported in clinical trials involving pancreatic enzyme therapy. No serious or other adverse events were reported. CONCLUSION: Treatment with Pancrease MT at a dosage of 500 U lipase/kg/meal resulted in a CFA of approximately 89% in pediatric subjects ages 6 to 30 months with PI resulting from CF. Pancrease MT doses were well tolerated and mean palatability was scored as fair to good. Present results do not indicate that a dosage higher than 500 U (Ph. EUR) lipase/kg/meal increases the coefficient of fat absorption in a cohort of infants 6 to 30 months of age.

Potential roles and clinical utility of prebiotics in newborns, infants, and children: proceedings from a global prebiotic summit meeting, New York City, June 27-28, 2008.

Initial bacterial colonization, including colonization with health-positive bacteria, such as bifidobacteria and lactobacilli, is necessary for the normal development of intestinal innate and adaptive immune defenses. The predominance of beneficial bacteria in the gut microflora of breast-fed infants is thought to be, at least in part, supported by the metabolism of the complex mixture of oligosaccharides present in human breast milk, and a more adult-type intestinal microbiota is found in formula-fed infants. Inadequate gut colonization, dysbiosis, may lead to an increased risk of infectious, allergic, and autoimmune disorders later in life. The addition of appropriate amounts of selected prebiotics to infant formulas can enhance the growth of bifidobacteria or lactobacilli in the colonic microbiota and, thereby, might produce beneficial effects. Among the substrates considered as prebiotics are the oligosaccharides inulin, fructo-oligosaccharides, galacto-oligosaccharides, and lactulose. There are some reports that such prebiotics have beneficial effects on various markers of health. For example, primary prevention trials in infants have provided promising data on prevention of infections and atopic dermatitis. Additional well-designed prospective clinical trials and mechanistic studies are needed to advance knowledge further in this promising field.

Infliximab therapy in children with concurrent perianal Crohn disease: observations from REACH.

OBJECTIVE: Post hoc analyses evaluated the effect of infliximab upon concurrent perianal Crohn disease (CD) in a subpopulation of 31 patients from REACH, a randomized trial of 112 children with moderately to severely active luminal CD. MATERIALS AND METHODS: The Pediatric Crohn Disease Activity Index perirectal subscore was used to assess perianal symptom activity and therapeutic response. Patients with no symptoms or asymptomatic tags received a score of 0; those with "1-2 indolent fistula, scant drainage, no tenderness" received a score of 5; and those with "active fistula, drainage, tenderness or abscess" received a score of 10. Initial perirectal subscores of 10 or 5 decreasing to 0 were considered complete response. Subscores of 10 decreasing to 5 were considered partial response. All patients were followed for efficacy and safety through week 54. RESULTS: Twenty-two patients with baseline perianal disease were randomized at week 10 following a 3-dose infliximab induction regimen. At week 2, 40.9% (9/22) of patients with signs and symptoms of perianal disease at baseline attained response (4 partial and 5 complete). At week 54, 72.7% (16/22) of patients with signs and symptoms of perianal disease attained response (1 partial and 15 complete). Nine patients developed perianal signs and symptoms during treatment; 7 had complete response and 2 had no response at week 54. The incidence of adverse events for patients with perianal symptoms at baseline and for those in the overall REACH population was similar (95.7% vs 94.6%). CONCLUSIONS: Infliximab rapidly reduced concurrent perianal disease signs and symptoms in this REACH cohort.

Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).

OBJECTIVE: To develop a North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) international consensus on the diagnosis and management of gastroesophageal reflux and gastroesophageal reflux disease in the pediatric population. METHODS: An international panel of 9 pediatric gastroenterologists and 2 epidemiologists were selected by both societies, which developed these guidelines based on the Delphi principle. Statements were based on systematic literature searches using the best-available evidence from PubMed, Cumulative Index to Nursing and Allied Health Literature, and bibliographies. The committee convened in face-to-face meetings 3 times. Consensus was achieved for all recommendations through nominal group technique, a structured, quantitative method. Articles were evaluated using the Oxford Centre for Evidence-based Medicine Levels of Evidence. Using the Oxford Grades of Recommendation, the quality of evidence of each of the recommendations made by the committee was determined and is summarized in appendices. RESULTS: More than 600 articles were reviewed for this work. The document provides evidence-based guidelines for the diagnosis and management of gastroesophageal reflux and gastroesophageal reflux disease in the pediatric population. CONCLUSIONS: This document is intended to be used in daily practice for the development of future clinical practice guidelines and as a basis for clinical trials.

Improvement in biomarkers of bone formation during infliximab therapy in pediatric Crohn's disease: results of the REACH study.

BACKGROUND & AIMS: Crohn's disease (CD) is associated with altered bone metabolism. This study examined changes in bone formation and resorption after infliximab induction and associations between bone biomarkers, linear growth, and disease activity (Pediatric Crohn's Disease Activity Index [PCDAI]) after 54 weeks of infliximab therapy. METHODS: One hundred twelve subjects ages 6-17 years with moderate to severe CD received infliximab induction (5 mg/kg/dose) at weeks 0, 2, and 6; week-10 responders were randomized to infliximab every 8 or every 12 weeks maintenance therapy. Serum bone-specific alkaline phosphatase (BSAP), N-terminal propeptide of type 1 collagen (P1NP), urine C-telopeptide of collagen cross-links (CTX-1), and deoxypyrodinoline (DPD) were collected at baseline and 10 weeks. PCDAI and height z-scores were assessed at baseline and at 10 and 54 weeks. RESULTS: Models were adjusted for bone age, gender, height, and steroid use. Baseline BSAP and P1NP levels were negatively associated with PCDAI (both P = .01). BSAP and P1NP increased during induction (both P < .001) and were associated with 54-week increases in height z-score (P < .05 and P < .001, respectively). Improvements in P1NP were associated with 54-week decreases in PCDAI (P = .01). CTX-1 and DPD also increased during induction (P < .001 and P = .01, respectively) but were not associated with changes in PCDAI. Changes in CTX-1 were associated with improvements in height z-score (P < .002). CONCLUSIONS: Infliximab therapy is associated with dramatic increases in BSAP and P1NP, consistent with inhibition of tumor necrosis factor-alpha effects on osteoblasts. The increases in CTX-1 and DPD likely reflect coupling of bone formation and resorption and increases in linear growth.

Malignancy and mortality in pediatric patients with inflammatory bowel disease: a multinational study from the porto pediatric IBD group.

BACKGROUND: The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. METHODS: A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006-2011. RESULTS: We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0-14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein-Barr virus-associated lymphomas. CONCLUSIONS: Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.

Comparison of outcomes parameters for induction of remission in new onset pediatric Crohn's disease: evaluation of the porto IBD group "growth relapse and outcomes with therapy" (GROWTH CD) study.

BACKGROUND: Robust evaluation of induction therapies using both clinical and inflammatory outcomes in pediatric Crohn's disease (CD) are sparse. We attempted to evaluate clinical, inflammatory, and composite outcomes of induction of remission therapies (normal C reactive protein [CRP] remission) in a large pediatric prospective multicenter study. METHODS: Patients enrolled at diagnosis into the growth relapse and outcomes with therapy in Crohn's disease study were evaluated for disease activity, CRP, and fecal calprotectin at 8, 12 and 52 weeks after starting treatment. The primary endpoint was week-12 steroid-free remission defined by pediatric Crohn's disease activity index and CRP <0.5 mg/dL. The protocol required tapering off corticosteroids by week 11. RESULTS: We analyzed 222 patients (mean age, 12.9 ± 3.2 yr) main evaluated treatment options included: 5-ASA (n = 29), exclusive enteral nutrition (n = 43), and corticosteroids (n = 114). Clinical remission at week 12 was achieved in 155 (73%) patients; both exclusive enteral nutrition and steroids were associated with normal CRP remission at week 12, although in a post hoc subgroup analysis exclusive enteral nutrition was superior in mild-to-moderate disease for this outcome. Among those in steroid-free remission in week 12, normal CRP predicted 1-year sustained remission (86% for normal CRP versus 61% for elevated CRP; P = 0.02). Baseline severity and early immunomodulation were similar in both groups. CONCLUSIONS: Normal CRP steroid-free remission at week 12 was impacted by type of induction therapy, but not by early immunomodulation. It was associated with more corticosteroids-free remission at week 52 and a trend for less relapses.

Probiotics and IBD.

The pathophysiology of inflammatory bowel disease is still incompletely understood. While the development of the immune system and the establishment of the microflora take place during infancy young patients often have a more severe and extensive disease. The differences in composition and concentration of intestinal microbiota and aberrant immune responses towards the luminal bacteria prompted the concept of an 'ecological' approach to control the disease course. Probiotics, living, non pathogenic micro organisms with a beneficial effect on the host, and prebiotics, oligosaccharides promoting the growth of the beneficial microflora, have been studied to this effect. Results have so far been disappointing for Crohn's disease but encouraging for ulcerative colitis. An overview of studies using probiotics in adults or children and a perspective on specific pediatric issues is provided in this review.

Diagnosis and management of cow's milk protein allergy in infants.

BACKGROUND: Cow's milk protein allergy (CMPA) is frequently suspected in infants with a variety of symptoms. A thorough history and careful clinical examination are necessary to exclude other underlying diseases and to evaluate the severity of the suspected allergy. Care should be taken to diagnose CMPA adequately to avoid an unnecessary diet. DATA SOURCES: We make recommendations based on systematic literature searches using the best-available evidence from PubMed, Cumulative Index to Nursing and Allied Health Literature, and bibliographies. RESULTS: Skin prick tests, patch tests and serum specific IgE are only indicative of CMPA. Breastfed infants have a decreased risk of developing CMPA; an elimination diet for the mother is indicated if CMPA is confirmed. If a food challenge is positive in formula fed infants, an extensively hydrolysed formula and cow's milk-free diet is recommended. If symptoms do not improve, an amino acid based formula should be considered. In severe CMPA with life-threatening symptoms, an amino-acid formula is recommended. CONCLUSIONS: Elimination diet by a double-blind placebo controlled food challenge is the gold standard for diagnosis. Elimination of the offending allergen from the infants' diet is the main treatment principle.

Milk fat globule membrane (INPULSE) enriched formula milk decreases febrile episodes and may improve behavioral regulation in young children.

OBJECTIVE: Polar lipids constitute an important part of cellular membranes. The mucosal surface of the gastrointestinal tract is a critical barrier between noxious and immunogenic substances in the lumen and the mucosal immune system. METHODS: We conducted a prospective, double-blinded, randomized, controlled trial in healthy children to evaluate the acceptability, safety, effect on intestinal comfort (constipation), common infectious symptoms (fever, diarrhea, cough), and behavioral regulation of a 4-mo daily intake of 200-mL formula with or without enrichment of the milk fat globule membrane (INPULSE). Data were collected from parental diaries. The primary endpoints for analysis were the number of days with fever, diarrhea, coughing, or constipation. The secondary endpoints were the number of doctor visits, medication intake, number of missed schooldays, acceptability of the test drinks, and safety. The Achenbach System of Empirically Based Assessment, a validated questionnaire to assess behavior, was submitted to parents at the end of the intervention period. RESULTS: Initially 253 children were included, but 71 dropped out (these were subjects with <80% intake or for <90 d). No adverse effects led to the discontinuation. Per-protocol analysis was performed in 97 girls and 85 boys. The group (n = 182) was normally distributed, with a mean age of 4.4 ± 0.9 y. The amount of product taken each day and the acceptability were similar in the intervention and control groups. The number of days with fever (>38.5°C) and the number of short (<3 d) febrile periods were significantly (P < 0.03) decreased in the intervention group (1.7 ± 2.5 vs 2.6 ± 3.1 d) This significant difference in febrile episodes appeared after 6 wk of consecutive intake. Other outcome parameters (diarrhea, constipation, cough, doctor visit, and days of school absence) were similar in the two groups. An analysis of the 169 Achenbach System of Empirically Based Assessment questionnaires (two-tailed t test) showed significant differences in the internal (P < 0.003), external (P < 0.004), and total (P < 0.002) problem scores in favor of the intervention group. Between-subjects effects were highly correlated (internal, P < 0.003; external, P < 0.005; total, P < 0.002, one-way analysis of variance). CONCLUSION: Regular consumption of formula enriched with a concentrated milk fat membrane (INPULSE) product by preschool children was safe, well tolerated, and, based on per-protocol analysis, is associated with a significant decrease in the number of short febrile episodes and leads to improved behavioral regulation.

Safety and efficacy of maintenance infliximab therapy for moderate-to-severe Crohn's disease in children: REACH open-label extension.

OBJECTIVE: Assess long-term effects of maintenance infliximab therapy in children with moderately-to-severely active Crohn's disease. RESEARCH DESIGN AND METHODS: One hundred twelve patients with a Pediatric Crohn's Disease Activity Index (PCDAI) score >30 received infliximab 5 mg/kg at weeks 0, 2, and 6 in the REACH study. Patients considered responders at week 10 were randomized to infliximab 5 mg/kg every 8 (q8w) or 12 (q12w) weeks. Patients who completed treatment through week 46, and who the investigator believed would benefit from continued treatment, could enter the open-label extension (OLE) and receive up to three additional years of infliximab. No hypothesis testing was performed. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, identifier: NCT0020767. RESULTS: Sixty children entered the OLE: 33, 12, and 15 patients were receiving infliximab 5 mg/kg q8w, 5 mg/kg q12w, and 10 mg/kg q8w, respectively, at extension entry. Patients receiving infliximab for up to 3 years during the OLE maintained clinical benefit, with approximately 80% of patients consistently having no to mild disease activity per the physician's global assessment and very good to fair health in the past 2 weeks per the patient and parent/guardian global assessments. Patients with ≥1-year delay in bone age at baseline trended toward improvement in height during the OLE. Respiratory system disorders, most commonly upper respiratory infections, were the most prevalent adverse events reported; six (10%) patients had serious infections. CONCLUSIONS: Among children with moderately-to-severely active Crohn's disease who received infliximab for 46 weeks in REACH and then for up to 3 additional years in the REACH OLE, infliximab was effective in maintaining clinical benefit and was generally well-tolerated.

Results from the 2nd Scientific Workshop of the ECCO. I: Impact of mucosal healing on the course of inflammatory bowel disease.

Over the past years, mucosal healing has emerged as a major therapeutic goal in clinical trials in inflammatory bowel diseases. Accumulating evidence indicates that mucosal healing may change the natural course of the disease by decreasing the need for surgery and reducing hospitalization rates in both ulcerative colitis and Crohn's disease. Mucosal healing may also prevent the development of long-term disease complications, such as bowel damage in Crohn's disease and colorectal cancer in ulcerative colitis. Histologic healing may be the ultimate therapeutic goal in ulcerative colitis, whereas its impact on the course of Crohn's disease is unknown. Complete mucosal healing may be required before considering drug withdrawal. Targeting early Crohn's disease is more effective than approaches aimed at healing mucosa in longstanding disease. Several questions remain to be answered: should mucosal healing be systematically used in clinical practice? Should we optimize therapies to achieve mucosal healing? What is the degree of intestinal healing that is required to change the disease course? Large prospective studies addressing these issues are needed.

Gastric emptying in healthy newborns fed an intact protein formula, a partially and an extensively hydrolysed formula.

BACKGROUND & AIMS: Gastric emptying (GE) is influenced by the type of nutrition. The objective of this study was to compare GE in infants fed an intact protein formula (IPF), a partially hydrolysed formula (PHF), and an extensively hydrolysed formula (EHF). METHODS: This was a double-blind, randomized, cross-over study. Following a fasting period of > or = 3 h, 20 healthy newborns were fed IPF, PHF, and EHF containing 50 microl (13)C-octanoic acid (OA). Breath samples were taken before feeding and every 15 min for 4 h thereafter. (13)C-OA breath test was assessed by isotope-ratio mass spectrometry, and GE half-times (t(1/2)) were determined. RESULTS: Seventeen infants with a mean gestational age of 37 wk (range 28-40 wk) and birth weight of 2698 g (range 720-3690 g) completed the study. At study initiation, the mean age was 31 d (range 6 d-13 wk) and the mean weight was 3466 g (range 2100-5700 g). EHF emptied significantly faster than IPF and PHF (medians 46 vs. 55 and 53 min, respectively, Wilcoxon, P<0.05 for both). There was no significant difference between GE of PHF and IPF (Wilcoxon, P=0.2). CONCLUSIONS: EHF may be better tolerated by infants with GE problems.