Salvatore Oliva

Randomised clinical trial: the effectiveness of Lactobacillus reuteri ATCC 55730 rectal enema in children with active distal ulcerative colitis

Background  Intestinal microbiota manipulation, one of the pathogenetic components of inflammatory bowel disease (IBD), has become an attractive therapy for ulcerative colitis (UC).

Clinical and mucosal improvement with specific carbohydrate diet in pediatric Crohn disease.

Objective: The aim of the study was to prospectively evaluate clinical and mucosal responses to the specific carbohydrate diet (SCD) in children with Crohn disease (CD). Methods: Eligible patients with active CD (Pediatric Crohns Disease Activity Index [PCDAI] ≥ 15) underwent a patency capsule and, if passed intact, capsule endoscopy (CE) was performed. Patients taking SCD were monitored for 52 weeks while maintaining all prescribed medications. Demographic, dietary, and clinical information, PCDAI, Harvey-Bradshaw Index (HBI), and Lewis score (LS) were collected at 0, 12, and 52 weeks. CEs were evaluated by an experienced reader blinded to patient clinical information and timing. Results: Sixteen patients were screened; 10 enrolled; and 9 completed the initial 12-week trial—receiving 85% of estimated caloric needs before, and 101% on the SCD. HB significantly decreased from 3.3 ± 2.0 to 0.6 ± 1.3 (P = 0.007) as did PCDAI (21.1 ± 5.9 to 7.8 ± 7.1, P = 0.011). LS declined significantly from 2153 ± 732 to 960 ± 433 (P = 0.012). Seven patients continued the SCD up to 52 weeks; HB (0.1 ± 0.4) and PCDAI (5.4 ± 5.5) remained improved (P = 0.016 and 0.027 compared to baseline), with mean LS at 1046 ± 372 and 2 patients showed sustained mucosal healing. Conclusions: Clinical and mucosal improvements were seen in children with CD, who used SCD for 12 and 52 weeks. In addition, CE can monitor mucosal improvement in treatment trials for pediatric CD. Further studies are critically needed to understand the mechanisms underlying SCDs effectiveness in children with CD.

Intralesional steroid injection after endoscopic balloon dilation in pediatric Crohn's disease with stricture: A prospective, randomized, double-blind, controlled trial

BACKGROUND Endoscopic balloon dilation (EBD) is an attractive conservative therapy for Crohns disease (CD) with stricture; however, its long-term efficacy has been questioned because many patients require more dilations or postdilation surgery. Most reports are retrospective, and no pediatric data are available. OBJECTIVE To assess the effectiveness of corticosteroid intralesional injection after EBD in preventing stricture recurrence. DESIGN Single-center prospective, randomized, double-blind, controlled trial. SETTING Tertiary-referral university hospital. PATIENTS Between November 2005 and January 2009, 29 pediatric patients with stricturing CD were enrolled. INTERVENTIONS Enrolled patients were randomized to receive intrastricture injection of corticosteroid (CS) (n = 15) or placebo (n = 14) after EBD. Patients were followed clinically via small intestine contrast US and intestinal magnetic resonance imaging at 1, 3, 6, and 12 months; all underwent colonoscopy 12 months after dilation. MAIN OUTCOME MEASUREMENTS Time free of repeat dilation and time free of surgery in the 2 groups. RESULTS One of the 15 patients receiving CS required redilation, whereas the latter was needed in 5 of the 14 placebo patients; surgery was needed in 4 of the placebo patients, but in none of those receiving CS. The 2 groups statistically differed in the time free of redilation (P = .04) as well as for time free of surgery after EBD (P = .02), which were worse in the placebo group compared with the CS group. There were no significant differences in baseline demographics between the 2 groups. LIMITATIONS Sample size, participation bias, and short-term follow-up. CONCLUSION In pediatric CD with stricture, intralesional CS injection after EBD is an effective strategy for reducing the need both for redilation and surgery.

MR enterography versus capsule endoscopy in paediatric patients with suspected Crohn's disease.

ObjectiveThe aim of this prospective study was to compare the diagnostic yield of MR enterography (MRE) with small-bowel capsule endoscopy (SBCE) in paediatric patients with suspected Crohn’s disease (CD).MethodsPaediatric patients with suspected CD were considered eligible to be enrolled in the study. All patients underwent diagnostic work-up including 1.5-T MRE, ileo-colonoscopy and oesophagogastroduodenoscopy. SBCE was not performed if MRE showed SB stricture or extra-intestinal findings consistent with symptoms.ResultsSixty consecutive paediatric patients (36 male; average age 14) were enrolled into the study. A positive diagnosis for CD was made in 19 patients, 29 had a negative result and 12 were affected by other gastro-intestinal conditions. SBCE was performed in 37 patients (61.7%); 23 patients were excluded (strictures in five, extra-intestinal findings in 11 and parents’ refusal in seven cases). The accuracy, sensitivity, and specificity of MRE and SBCE were 98.3%, 100%, 97.6%, and 91.9%, 90.9%, 92.3%, respectively.ConclusionBoth MRE and SBCE are accurate methods for patients with suspected CD. MRE can be used as a primary imaging technique in suspected CD, in that it allows access to the ileal stricture, which forms a contra-indication for SBCE and provides extra-intestinal information.

Efficacy of Adalimumab in Moderate-to-Severe Pediatric Crohn's Disease

OBJECTIVES:The use of tumor necrosis factor-alpha (TNF-α) antagonists has changed the therapeutic strategy for Crohns disease (CD). Adalimumab (ADA), a fully human anti-TNF-α monoclonal antibody, is an effective therapy for patients with CD, both naive patients and those intolerant or refractory to Infliximab (IFX), a chimeric anti-TNF-α agent. However, the use of ADA is rarely reported in pediatric CD. We performed an open prospective evaluation of short- and long-term efficacy and safety of ADA in children with moderate-to-severe CD.METHODS:A total of 23 pediatric CD patients (9 naive and 14 intolerant or unresponsive to IFX) received ADA subcutaneously as a loading schedule at weeks 0 and 2, and at every other week (eow) during a 48-week maintenance phase. Loading and maintenance doses were 160/80 and 80 mg eow in 13 cases, 120/80 and 80 mg eow in 2, and 80/40 and 40 mg eow in 8 cases. The primary efficacy outcomes were clinical remission and response at different scheduled visits along the maintenance phase. At baseline, 13 patients also received immunomodulators (IMs).RESULTS:At weeks 2, 4, 12, 24, and 48, remission rates were 36.3, 60.8, 30.5, 50, and 65.2%, respectively, whereas response rates were 87, 88, 70, 86, and 91%, respectively. Four patients at week 24 and 2 at week 48 received IMs; the mean daily corticosteroid dose, disease activity index, C-reactive protein level, and erythrocyte sedimentation rate decreased significantly throughout the trial. No serious adverse events were recorded.CONCLUSIONS:ADA can be an effective and safe biological agent for inducing and maintaining remission in children with moderate-to-severe CD, even in those with previous IFX therapy.

Usefulness of single-balloon enteroscopy in pediatric Crohn's disease

BACKGROUND Single-balloon enteroscopy (SBE) has not been reported in pediatric Crohns disease (CD). OBJECTIVE To determine technical performance, yield, safety, and clinical impact of SBE in pediatric patients with suspected and established CD. DESIGN Prospective, cohort study. SETTING Academic tertiary-care referral center. PATIENTS This study involved 16 patients (group A) with suspected CD and unspecific upper and lower GI endoscopy results and 14 patients (group B) with longstanding CD with previous surgery and showing signs unaccountable by conventional endoscopy. All underwent magnetic resonance imaging, and 14 patients in group A also underwent wireless capsule endoscopy. INTERVENTION SBE. MAIN OUTCOME MEASUREMENTS SBE diagnostic and therapeutic yield, technical performance, clinical impact, and safety. RESULTS In group A, SBE aided diagnosis of CD in 12 patients and eosinophilic enteropathy in 2 patients, whereas no lesions were found in 2 patients. WCE was diagnostic of CD in 3 patients, suggestive of CD in 7 patients, and unspecific in the remaining patients. In group B, SBE revealed moderate-to-severe disease activity in most patients, leading to the introduction of or change in biological therapy, with a marked decrease in the pediatric Crohns disease activity index scores. SBE allowed successful dilation of small-bowel strictures in 2 patients in group A and 3 in group B. No complications occurred. LIMITATIONS Small sample size, no direct comparison with imaging or other endoscopic techniques. CONCLUSION SBE is a useful and safe endoscopic procedure for evaluating the small bowel in pediatric patients with suspected or established CD. Not only does it allow a definite diagnosis of CD when the latter is uncertain, but it is also very effective in the management of small-bowel strictures, thus avoiding surgery. It may be helpful in redirecting therapy in selected CD patients.

Lactobacillus reuteri ATCC55730 in cystic fibrosis.

Objectives: The aim of this study was to evaluate in patients with cystic fibrosis (CF) the effect of Lactobacillus reuteri (LR) on the rate of respiratory exacerbations and of the infections of both upper respiratory and gastrointestinal tracts. Methods: Prospective randomized, double-blind, placebo-controlled study enrolling 61 patients with CF with mild-to-moderate lung disease at the Regional Center for CF of the Department of Pediatrics, University of Rome “La Sapienza.” All of the patients were not hospital inpatients at the time of the enrollment. Inclusion criteria were forced expiratory volume in the first second (FEV1) >70% predicted; no inhaled or systemic steroids, no anti-inflammatory drugs, antileukotrienes, and mast cell membrane stabilizers; and no serious organ involvement. Exclusion criteria were a history of pulmonary exacerbation or upper respiratory infection in the previous 2 months; changes in medications in the last 2 months; a history of hemoptysis in the last 2 months; and colonization with Burkholderia cepacia or mycobacteria. Patients were randomly assigned to receive LR (30 patients) in 5 drops per day (1010 colony-forming units) or placebo (31 patients) for 6 months. Main outcomes were number of episodes of pulmonary exacerbations and hospital admissions for pulmonary exacerbations, number of gastrointestinal and upper respiratory tract infections. FEV1, fecal calprotectin, and cytokine profile in induced sputum and plasma were assessed at baseline and at the end of the trial. Results: Pulmonary exacerbations were significantly reduced in the LR group compared with the placebo group (P < 0.01; odds ratio 0.06 [95% confidence interval {CI} 0–0.40]; number needed to treat 3 [95% CI 2–7]). Similarly, the number of upper respiratory tract infections (in our series only otitis) was significantly reduced in the LR group compared with the placebo group (P < 0.05; odds ratio 0.14 [95% CI 0–0.96]; number needed to treat 6 [95% CI 3–102]). The 2 groups did not differ statistically in the mean number and duration of hospitalizations for pulmonary exacerbations and gastrointestinal infections. There was no significant statistical difference in the mean delta value of FEV1, fecal calprotectin concentration, and tested cytokines (tumor necrosis factor-&agr; and interleukin-8) between the 2 groups. Conclusions: LR reduces pulmonary exacerbations and upper respiratory tract infections in patients with CF with mild-to-moderate lung disease. LR administration may have a beneficial effect on the disease course of CF.

Second-generation colon capsule endoscopy vs. colonoscopy in pediatric ulcerative colitis: a pilot study

BACKGROUND AND STUDY AIMS Second-generation colon capsule endoscopy (CCE-2) may overcome the invasiveness of colonoscopy in the evaluation of mucosal inflammation, especially in pediatric ulcerative colitis. The aim of this pilot study was to determine the diagnostic accuracy of CCE-2 in evaluating disease activity, using colonoscopy as a gold standard. Disease extent, tolerability, interobserver agreement, and safety were also evaluated. METHODS A total of 30 consecutive pediatric patients with ulcerative colitis were prospectively enrolled (mean age 14.1 ± 3.2 years). Patients underwent CCE-2 followed by colonoscopy in the late afternoon or the following day. The blinded procedures were performed, and the diagnostic accuracy of CCE-2 to assess disease activity was determined using a modified Matts score, which classified patients as either normal (Matts score ≤ 6) or with active inflammation (Matts score > 6). Interobserver agreement was assessed using the kappa statistic. RESULTS One patient was excluded from the analysis because they were unable to swallow the capsule, leaving 29 patients available for analysis. The sensitivity of CCE-2 for disease activity was 96 % (95 % confidence interval [CI] 79 - 99) and specificity was 100 % (95 %CI 61 - 100). The positive and negative predictive values of CCE-2 were 100 % (95 %CI 85 - 100) and 85 % (95 %CI 49 - 97), respectively. No serious adverse events were reported. CCE-2 had a higher overall tolerability than colonoscopy (P < 0.05). Interobserver agreement was excellent in all cases (κ > 0.86). CONCLUSIONS Using a modified Matts score, CCE-2 was accurate in evaluating significant mucosal inflammation in children with ulcerative colitis. TRIAL REGISTRATION ClinicalTrials.gov--NCT01740349.

Neuroimmune interactions at different intestinal sites are related to abdominal pain symptoms in children with IBS

Neuroimmune interactions and inflammation have been proposed as factors involved in sensory‐motor dysfunction and symptom generation in adult irritable bowel syndrome (IBS) patients. In children with IBS and healthy controls, we measured ileocolonic mast cell infiltration and fecal calprotectin and evaluated the relationships between these parameters and abdominal pain symptoms and stooling pattern.

Pneumatic balloon dilation in pediatric achalasia: efficacy and factors predicting outcome at a single tertiary pediatric gastroenterology center

BACKGROUND The use of pneumatic dilation (PD) is well established in adults with achalasia; however, it is less commonly used in children. OBJECTIVE To evaluate the efficacy of PD in pediatric achalasia and to define predictive factors for its treatment failure. DESIGN Single-center, prospective cohort study. SETTING Academic tertiary referral center. PATIENTS Twenty-four patients with achalasia were enrolled from January 2004 to November 2009 and were followed for a median of 6 years. INTERVENTION PD was performed with the patients under general anesthesia. MAIN OUTCOME MEASUREMENTS Efficacy and safety of PD. Follow-up was performed by using the Eckardt score, barium swallow contrast studies, and esophageal manometry at baseline; 1, 3, and 6 months after dilation; and every year thereafter. A Cox regression model was used to identify independent predictors of failure after the first PD. RESULTS The PD success rate was 67%. In 8 patients, the first PD failed, but the parents of one patient refused a second PD and requested surgery. Of the 7 patients who underwent repeated treatment, the second PD failed in 3 (43%). Overall, only 3 of the 24 patients underwent surgery (overall success rate after a maximum of 3 PDs was 87%). Multivariate analysis showed that only older age was independently associated with a higher probability of the procedure success (hazard ratio [HR] 0.66; 95% CI, 0.45-0.97). LIMITATIONS Small sample size, single-center study. CONCLUSIONS PD is a safe and effective technique in the management of pediatric achalasia. Young age is an independent negative predictive factor for successful clinical outcome.