Clinical significance and sonographic evolution of enlarged abdominal lymph nodes in children.

AIM: Paediatric evidence about the clinical implications of enlarged abdominal lymph nodes (EALN) is not univocal. The main purpose of our study was to evaluate the clinical significance and the morphological evolution of enlarged abdominal nodes in children with recurrent abdominal pain. METHODS: All children with recurrent abdominal pain diagnosed with EALN were enrolled at the involved centres between September 2017 and June 2018. Number, size, localisation, shape and architecture of nodes were accurately recorded along with clinical and laboratory data at enrolment and after three and six months. RESULTS: A total of 38 children were enrolled. After the six-month study period, 58% of them had lymph nodes reduced in size, 13% had unchanged lymph nodes, and 29% had lymph nodes increased in size. Overall, we observed a gradual, albeit slight reduction in the average size of enlarged nodes over the six-month period. The extent of size changes was not correlated with any clinical parameter. CONCLUSION: Our data suggest that EALN are a non-specific finding, which is not worth a change in the diagnostic and therapeutic management of children with abdominal pain.

Successful outcome of the transitional process of inflammatory bowel disease from pediatric to adult age: A five years experience.

INTRODUCTION AND AIM: The transitional process of young patients affected by inflammatory bowel disease from pediatric to adult care is a crucial step. Our study aimed to investigate the 1-year success outcome of this transitional process. METHODS: From 2013 to 2018, we evaluated the transitional process of patients with Crohn's disease or ulcerative colitis. For each patient, the following parameters 12 months before and 12 months after the transition were evaluated: Body Mass Index, disease activity and smoker status, number of outpatient visits and the pharmacological therapy, the number of disease exacerbations, hospitalizations and surgical interventions. RESULTS: We enrolled 106 patients with IBD. No statistically significant difference was found between patients' Body Mass Index before and after transition. There was a significant reduction in the number of exacerbations and hospitalizations in the 12 months post-transition (pre-transition exacerbations: 0.74 ±â€¯0.79, post-transition exacerbations: 0.35 ±â€¯0.57, p < 0.001; pre-transition hospitalizations: 0.28 ±â€¯0.44, post-transition hospitalizations: 0.1 ±â€¯0.3, p < 0.001). In contrast, there was no significant difference in the number of outpatient visits (3.40 ±â€¯1.4 vs 3.25 ±â€¯1.2; p = ns) and of patients undergoing surgery (0.9% vs 1.8%, p = ns). CONCLUSION: The parameters used as success indicators of the transition program confirm the achievement of continuity of care from Pediatrics to adult Gastroenterology, in a critical phase of the natural history of IBD patients.

Oral administration of tannins and flavonoids in children with acute diarrhea: a pilot, randomized, control-case study.

BACKGROUND: AG is the most common cause of pediatric consultations among children between 2 and 5 years of age and it still leads to high mortality and morbidity. Its management is based on rehydration therapy, but this treatment is not effective in reducing duration of diarrhea. For this reason, other safer and less expensive interventions, which could be added to oral rehydration therapy, are of great interest. METHODS: A pilot, randomized, case-controlled trial was conducted in 60 children affected by AG (< 7 days) with mild-moderate dehydration, according to WHO recommendations, from1 year to 17 years old. Patients were divided into 2 Groups: Group 1 consisting of 30 children treated with Actitan F and standard oral rehydration (SOR); Group 2 consisting of 30 children who received only SOR. Both groups received treatment for seven days, respectively. Patients of Group 1 stopped for their own choice, SOR after the first 24 h and continued only with Actitan F. RESULTS: After 24 h of treatment, the median number of stools was 3.5 for Group 1, and 4 for Group 2. In Group 1 the difference between the number of stools at baseline (n = 5) and after 24 h of treatment (n = 3.5) was significant (p < 0.0001). At the end of treatment, the median duration of diarrhea in Group 1 was 5 days, compared with 4 days in the Group 2, this difference was not statically significant (p 0.48). CONCLUSIONS: Oral administration of Actitan F associated with SOR seems safe and effective treatment in shortening the duration of AG in children. Further studies confirming these data are needed. TRIAL REGISTRATION: NCT03356327 (retrospectively registered).

The Changing Face of Pediatric Ulcerative Colitis: A Population-based Cohort Study.

OBJECTIVES: The aims of this retrospective study were to describe ulcerative colitis (UC) phenotype at diagnosis and follow-up and to identify possible predictors of severe disease course. METHODS: This was a retrospective, single-center study. We reviewed the charts of patients with UC diagnosed between 2 and 18 years at our referral center from January 2007 to January 2016. Laboratory and clinical features at diagnosis, such as disease extent, atypical phenotypes, extraintestinal manifestations, and therapies, and pattern changes during the follow-up, including relapse rate, disease extension, and the cumulative risk for colectomy were collected. RESULTS: One hundred eleven patients were enrolled. Atypical phenotypes were identified at diagnosis in 55 out of 111 patients (49.5%). Extraintestinal manifestations were detected in 16 out of 111 (14.4%) at the diagnosis. During the follow-up 60 out of 111 (54%) patients needed to start azathioprine, 9 out of 111 (8.1%) patients started biologic therapy and 10 out of 111 (patients underwent surgery, resulting in a cumulative risk of 8% at 5 years and 16% at 10 years. Steroid refractoriness (hazard ratio: 13.9) and starting of biologic therapy (hazard ratio: 25.3) represented the best predictors for surgery. The cumulative probability of first relapse was 47% at 6 months and 63% at 1 year. Disease extension was reported in 21 out of 70 patients (30%). CONCLUSION: Pediatric UC is associated with a severe phenotype and a high percentage of atypical features. Surgery rate seems to be decreased from early reports.

Do Children Just Grow Out of Irritable Bowel Syndrome?

OBJECTIVE: Few data exist on natural history of irritable bowel syndrome (IBS) in children; therefore we investigated symptoms evolution over time in a cohort of children with IBS. STUDY DESIGN: In this observational, single-center study, we prospectively enrolled newly diagnosed children with IBS and reassessed them after 24 months. At both time points, patients completed a symptoms questionnaire, and a score of stool consistency was obtained. The therapeutic strategy adopted was also recorded. RESULTS: Eighty-three children (age 11 years, range, 4-16.6 years; 53 males) completed the study. Forty-seven (56.6%) patients received no medical treatment, whereas polyethylene glycol, probiotics, and trimebutine were prescribed to 9 (10.8%), 24 (28.9%), and 3 (3.6%) subjects, respectively. Twenty-four months after diagnosis, 48 children (57.8%) reported resolution of symptoms (P <.001), without differences between sexes (P = .35) or among IBS subtypes (P = .49). Of these, 30 (62.5%) had been only reassured and 18 (37.5%) had been prescribed medical treatment (P = .26). Despite not being statistically significant, symptoms resolution was more common in patients receiving no medical treatment than in those receiving probiotics (63.8% vs 41.6%, P = .08). Among patients with constipation-IBS, no difference was found in symptoms resolution between patients receiving polyethylene glycol and those receiving no medical treatment (67% and 40%, respectively, P = 1). CONCLUSIONS: Children with IBS are likely to show spontaneous symptoms resolution over a 24-month follow-up, regardless of sex, age, impact of symptoms on daily activities, and IBS subtypes.

A Mixture of 3 Bifidobacteria Decreases Abdominal Pain and Improves the Quality of Life in Children With Irritable Bowel Syndrome: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

GOALS: We assessed the efficacy of a probiotic mixture of Bifidobacterium infantis M-63, breve M-16V, and longum BB536 in improving abdominal pain (AP) and quality of life (QoL) in children with irritable bowel syndrome (IBS) and functional dyspepsia (FD). BACKGROUND: AP-associated functional gastrointestinal disorders, particularly IBS and FD, are common in pediatrics, and no well-established treatment is currently available. Although probiotics have shown promising results in adults, data in children are heterogeneous. STUDY: Forty-eight children with IBS (median age, 11.2 y; range, 8 to 17.9 y) and 25 with FD (age, 11.6 y; range, 8 to 16.6 y) were randomized to receive either a mixture of 3 Bifidobacteria or a placebo for 6 weeks. After a 2-week "washout" period, each patient was switched to the other group and followed up for further 6 weeks. At baseline and follow-up, patients completed a symptom diary and a QoL questionnaire. AP resolution represented the primary outcome parameter. RESULTS: In IBS, but not in FD, Bifidobacteria determined a complete resolution of AP in a significantly higher proportion of children, when compared with placebo (P=0.006), and significantly improved AP frequency (P=0.02). The proportion of IBS children with an improvement in QoL was significantly higher after probiotics than after placebo (48% vs. 17%, P=0.001), but this finding was not confirmed in FD. CONCLUSIONS: In children with IBS a mixture of Bifidobacterium infantis M-63, breve M-16V, and longum BB536 is associated with improvement in AP and QoL. These findings were not confirmed in FD subjects. Trial identifier: NCT02566876 (http://www.clinicaltrial.gov).

Probiotics for Irritable Bowel Syndrome: Clinical Data in Children.

PURPOSE OF REVIEW: The purpose of this review was to summarize the evidence regarding probiotics treatment for pediatric IBS. RECENT FINDINGS: The overall management of children with IBS should be tailored to the patient's specific symptoms and identifiable triggers. The four major therapeutic approaches include: pharmacologic, dietary, psychosocial, and complementary/alternative medicine interventions.Although there is limited evidence for efficacy of pharmacological therapies such as antispasmodics and anti-diarrheals, these may have a role in severe cases. A Cochrane review concluded that only weak evidence exists regarding beneficial effects of pharmacological agents in providing relief from symptoms in functional abdominal pain (AP) in children. Role of antibiotics in treatment of children with IBS remains controversial. Various non-pharmacologic treatments are available for pediatric IBS. In a recent systematic review including 24 studies some evidence was found indicating beneficial effects of partially hydrolyzed guar gum (PHGG), cognitive behavioral therapy, hypnotherapy, and probiotics (LGG and VSL#3).Few randomized clinical trials (RCTs) are available in children. A meta-analysis including 9 trials which tested different probiotics as a treatment for Functional Gastrointestinal Disorders (FGIDs) in children and adolescents concluded that Lactobacillus GG, Lactobacillus reuteri DSM 17938 and VSL#3 significantly increased treatment success. We recently showed that, in children with IBS, a mixture of Bifidobacterium infantis M-63®, breve M-16V® and longum BB536® is safe and is associated with better AP control and improved quality of life when compared to placebo. SUMMARY: Probiotics are emerging as new therapeutic tools in FGIDs, due to the recognition of the importance of gut microbiota in influencing brain-gut interactions, and of the role played by intestinal infections in the genesis of AP-FGIDs. Preclinical data suggest that changes in the gut microbiota can affect brain signaling systems related to pain and associated emotional behavior. Therefore, probiotics could play a relevant role in the management of FGIDs, by affecting the gut microbiota or by altering brain function and pain perception centrally.

Autophagy genes variants and paediatric Crohn's disease phenotype: a single-centre experience.

BACKGROUND AND AIMS: Little evidence demonstrating the correlation between several single nucleotide polymorphisms and a specific phenotype of Crohn's disease has been reported in children. We investigated the relationship between autophagy genes variants and clinical features in our children with Crohn's disease. METHODS: Genotyping for ATG16L1, NOD2/CARD15, and IRGM1 was performed in 80 consecutive patients with Crohn's disease (median age: 11 years; range: 0.7-17.9 years). Crohn's disease location and behaviour were classified using the Paris classification. Additional data were collected from clinical records on patients' demographics, age at symptom onset and diagnosis, extraintestinal manifestations, therapy, clinical relapses, and need of surgical intervention. RESULTS: Patients homozygous for the risk allele ATG16L1 (T300A) showed a trend towards switching to a stricturing phenotype during the course of disease compared to children either homozygous for the wild-type allele or heterozygous for the ATG16L1 single nucleotide polymorphism (p=0.01). Homozygosity for the ATG16L1 risk allele was associated with a major recurrence of clinical relapses and earlier introduction of immunosuppressants (p=0.006 and p=0.04, respectively). Heterozygosity for the NOD2 rs2066847 allele was associated with major ileal involvement (p=0.01). CONCLUSION: In patients carrying the T300A variant, Crohn's disease follows a more aggressive clinical course.

Subtypes of irritable bowel syndrome in children: prevalence at diagnosis and at follow-up.

OBJECTIVES: To assess the prevalence of irritable bowel syndrome (IBS) subtypes in childhood at diagnosis and their changes over 1 year. STUDY DESIGN: This is an observational, prospective, multicenter study. Consecutive pediatric patients with IBS, according to Rome III criteria, were enrolled over a 1-year period. Parents recorded weekly stool frequency and consistency and gastrointestinal and extraintestinal symptoms in a diary. Stool consistency was scored according to the Bristol Stool Form Scale. Children were evaluated after 2, 3, 6, and 12 months. RESULTS: We enrolled 100 children with IBS (median age 9.9 years, range 4.2-16.7 years, 52 girls and 48 boys). At time of enrollment, constipation-IBS was the prevalent subtype (45%), with a prevalence of girls at 62% (P < .005); diarrhea-IBS was reported in 26% of children, with a prevalence of boys at 69% (P < .005); and alternating-IBS was described in 29% of children, without a difference between sexes. During the follow-up, 10% of patients changed their IBS subtypes at 2 months, 9% at 3 months, 7% at 6 months, and 6.3% at 12 months. Twenty-four percent of patients changed IBS subtype between the time of enrollment and 12 months. CONCLUSIONS: Constipation-IBS is the prevalent subtype in children, with a higher frequency in girls. In boys, diarrhea-IBS is the most common subtype. It is important to acquire knowledge about IBS subtypes to design clinical trials that may eventually shed new light on suptype-specific approaches to this condition.

Periappendiceal inflammation in pediatric ulcerative colitis.

BACKGROUND: An involvement of the appendiceal orifice as a distintive skip lesion in adults with left side ulcerative colitis (UC) has been reported. The aim of our prospective study was to evaluate, by endoscopy and histology, the prevalence of periappendiceal inflammation (PAI) in children affected by UC. METHODS: Fifty of 77 consecutive children undergoing total colonoscopy, who had a diagnosis of UC not extended beyond the hepatic flexure were enrolled. RESULTS: PAI was endoscopically present in 16 of 50 patients (32%) with UC. Patients were divided in 2 groups: group A included the 16 patients with PAI, whereas group B included 34 patients without PAI. We found that among the 2 groups, PAI was more frequent in patients with new diagnosis than in those with pre-existing UC (P = 0.016). At index colonoscopy, the patients of group A had a significant major extent of disease (P = 0.013). Moreover, the histologic grade of inflammation at the ascending colon was significantly higher in group A than in group B (P = 0.014). Clinical activity, measured by pediatric ulcerative colitis activity index, and use of medication did not show significant differences among groups (P = 0.464 and P = 0.723, respectively). The use of immunosuppressant was significantly higher in group A than in group B. CONCLUSIONS: PAI is a frequent skip lesion in children with UC. It seems more frequent in patients with new diagnosis, and it is associated with a major extent of the disease and with a higher grade of histologic inflammation at the ascending colon.

Does cow's milk protein elimination diet have a role on induction and maintenance of remission in children with ulcerative colitis?

AIM: Aims of this study were to evaluate the efficacy of a cow's milk protein (CMP) elimination diet on induction and maintenance of remission and to define association with atopy in children with ulcerative colitis (UC). METHODS: Twenty-nine consecutive patients (mean age: 11.2 years; range: 4.6-17 years; F/M: 15/14) with newly diagnosed UC were randomized either to receive a CMP elimination diet (n = 14) or to continue a free diet (n = 15) associated with concomitant steroid induction and mesalazine maintenance treatment. Children were prospectively evaluated at four time points: within 1 month, 6 months and 1 year after diagnosis or at the time of relapse. RESULTS: Twenty-five of the 29 enrolled patients responded to the UC induction therapy with a complete remission (86.2%), 13 belonging to CMP elimination diet group and 12 to free diet group (p = 0.59). Overall, our data showed that 7 of 13 (53.8%) patients treated with CMP elimination diet and 8 of 15 (53.3%) patients on free diet and UC therapy relapsed within 1 year of follow-up (p = 1). CONCLUSIONS: In conclusion, data of this paediatric, randomized trial suggest that CMP elimination has no role in the management of UC in non-sensitized children.

A randomized, prospective, comparison study of a mixture of acacia fiber, psyllium fiber, and fructose vs polyethylene glycol 3350 with electrolytes for the treatment of chronic functional constipation in childhood.

OBJECTIVES: To compare the effectiveness of a mixture of acacia fiber, psyllium fiber, and fructose (AFPFF) with polyethylene glycol 3350 combined with electrolytes (PEG+E) in the treatment of children with chronic functional constipation (CFC); and to evaluate the safety and effectiveness of AFPFF in the treatment of children with CFC. STUDY DESIGN: This was a randomized, open label, prospective, controlled, parallel-group study involving 100 children (M/F: 38/62; mean age ± SD: 6.5 ± 2.7 years) who were diagnosed with CFC according to the Rome III Criteria. Children were randomly divided into 2 groups: 50 children received AFPFF (16.8 g daily) and 50 children received PEG+E (0.5 g/kg daily) for 8 weeks. Primary outcome measures were frequency of bowel movements, stool consistency, fecal incontinence, and improvement of other associated gastrointestinal symptoms. Safety was assessed with evaluation of clinical adverse effects and growth measurements. RESULTS: Compliance rates were 72% for AFPFF and 96% for PEG+E. A significant improvement of constipation was seen in both groups. After 8 weeks, 77.8% of children treated with AFPFF and 83% of children treated with PEG+E had improved (P = .788). Neither PEG+E nor AFPFF caused any clinically significant side effects during the entire course of the study period. CONCLUSIONS: In this randomized study, we did not find any significant difference between the efficacy of AFPFF and PEG+E in the treatment of children with CFC. Both medications were proved to be safe for CFC treatment, but PEG+E was better accepted by children.

Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis.

OBJECTIVES: Several probiotic compounds have shown promise in the therapy of ulcerative colitis (UC). However, a strong sustained benefit remains to be seen. Uncontrolled pilot studies suggest that a probiotic preparation (VSL#3) maintains remission in mild to moderate UC and reduces active inflammation in adult patients. Aims of our prospective, 1-year, placebo-controlled, double-blind study were to assess the efficacy of VSL#3 on induction and maintenance of remission and to evaluate the safety and tolerability of the probiotic preparation therapy in children with active UC. METHODS: A total of 29 consecutive patients (mean age: 9.8 years; range: 1.7-16.1 years; female/male: 13/16) with newly diagnosed UC were randomized to receive either VSL#3 (weight-based dose, range: 450-1,800 billion bacteria/day; n=14) or an identical placebo (n=15) in conjunction with concomitant steroid induction and mesalamine maintenance treatment. Children were prospectively evaluated at four time points: within 1 month, 2 months, 6 months, and 1 year after diagnosis or at the time of relapse. Lichtiger colitis activity index and a physician's global assessment were used to measure disease activity. At baseline, within 6 months and 12 months or at the time of relapse, all patients were assessed endoscopically and histologically. RESULTS: All 29 patients responded to the inflammatory bowel disease (IBD) induction therapy. Remission was achieved in 13 patients (92.8%) treated with VSL#3 and IBD therapy and in 4 patients (36.4%) treated with placebo and IBD therapy (P<0.001). Overall, 3 of 14 (21.4%) patients treated with VSL#3 and IBD therapy and 11 of 15 (73.3%) patients treated with placebo and IBD therapy relapsed within 1 year of follow-up (P=0.014; RR=0.32; CI=0.025-0.773; NNT=2). All 3 patients treated with VSL#3 and 6 of 11 (54.5%) patients treated with placebo relapsed within 6 months of diagnosis. At 6 months, 12 months, or at time of relapse, endoscopic and histological scores were significantly lower in the VSL#3 group than in the placebo group (P<0.05). There were no biochemical or clinical adverse events related to VSL#3. CONCLUSIONS: This is the first pediatric, randomized, placebo-controlled trial that suggests the efficacy and safety of a highly concentrated mixture of probiotic bacterial strains (VSL#3) in active UC and demonstrates its role in maintenance of remission.