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Introduction Esophageal mucosa innervation in adults with nonerosive reflux disease (NERD) is more superficial compared with healthy volunteers. We delineated the esophageal mucosal innervation in pediatric NERD and controls. Methods Distal and proximal pediatric esophageal biopsies were immunohistochemically stained with calcitonin gene-related peptide and transient receptor potential cation channel subfamily V member 1. Results Mucosal innervation was assessed in 18 controls (9M:9F, median age: 9 years) and 11 NERD patients (6M:5F, median age: 5 years). Calcitonin gene-related peptide positive nerve fibers were lying deep in the mucosa in both groups, P > 0.05 and did not coexpress transient receptor potential cation channel subfamily V member 1. Discussion The pediatric esophageal mucosa in NERD displays deep lying nerve fibers, in contrast to adults.

Background High-resolution anorectal manometry (HR-ARM) is expected to be better than conventional manometry. Our aim was to characterize HR-ARM pressures in children with functional constipation (FC), with or without fecal incontinence (FI). Methods Children with diagnosis of FC, with or without FI, according to Rome-IV criteria, were enrolled. All patients underwent HR-ARM using 24-channel water-perfused catheter. Results Twenty-nine consecutive children (M/F: 21/8; mean age ± SD: 9.5 ± 3.1 years; range 4-15), of whom 21 affected by FC without FI (mean age ± SD: 9.3 ± 3.23 years) and 8 affected by FC with FI (mean age ± SD: 10.2 ± 3.08 years), were enrolled. No significant differences were found regard to gender and age. The analysis of HR-ARM 3D plots demonstrated asymmetry of the anal canal, with higher pressures in distal halves. Comparing pressures between the two groups, we found lower values in FC with FI than in FC without FI group, with a statistically significance for maximum and mean resting pressures (P = .032 and P = .008, respectively). When evaluating our study population respect to asymptomatic children, we found lower resting pressures, lower maximum squeeze pressure, and higher rectoanal inhibitory reflex (RAIR) values. Conclusions Our data demonstrate that HR-ARM pressures at rest and during squeezing in FC with FI children are lower than FC without FI subjects, particularly in anteroposterior quadrants. Compared to children without lower gastrointestinal symptoms, children with FC with or without FI show lower pressures and higher values of RAIR.

Aim: Postural measures are frequently recommended for gastroesophageal reflux (GER) symptoms, despite limited evidence. This was the first study to assess the impact of upright and recumbent body positions on GER episodes in children and adolescents, not just infants. Methods: We retrospectively assessed the pH-impedance parameters of paediatric patients referred for possible GER-related symptoms to two hospitals in Naples and Rome, Italy, from September 2016 to September 2018. Data were separately obtained for the time that the patients spent in upright and recumbent positions. Results: Data from 187 patients under the age of 18 were collected, at a mean age of just over seven years. We found that the acid exposure time was stable irrespective of changes in body position (P >.05). The mean number of reflux episodes per hour was 2.99 during the upright position and 1.21 during the recumbent position (P

We sought to correlate hepcidin levels in inflammatory bowel disease [IBD] children with disease activity, inflammatory markers, and iron load test [ILT] and to compare IBD patients with coeliac and healthy patients.Between December 2012 and June 2013, 145 subjects [50 IBD patients, 45 coeliac patients and 50 healthy controls] were included in the study. All patients underwent the following examinations: blood count, iron status, erythropoiesis parameters, serum hepcidin, C-reactive protein [CRP], and erythrocyte sedimentation rate [ESR]. In order to evaluate the efficacy of iron absorption, ILT was performed in IBD patients. Disease activity indexes and IBD duration, localisation, and therapy were also evaluated, and a faecal sample for calprotectin collected.Serum hepcidin was significantly higher in IBD patients with active disease compared with both coeliac and healthy patients [p = 0.005, p = 0.003 respectively]. In a multivariate logistic regression model, having a Paediatric Crohn's Disease Activity Index [PCDAI] / Paediatric Ulcerative Colitis Activity Index [PUCAI] ≥ 30 resulted in the only variable independently associated with a positive serum hepcidin (odds ratio [OR] = 6.87; 95% confidence interval [CI] 1.4-33, p = 0.01]]. Patients with iron malabsorption [IM] showed higher values of ESR, CRP, and hepcidin [p = 0.02, p = 0.001, and p = 0.06, respectively]. Eight out of 12 [66.7%] children with IM showed an active disease compared with 6/31 [19.3%] children with normal ILT [p = 0.01]. Hepcidin levels correlated negatively with ILT [r = -0.451, p = 0.002], and positively with ferritin and CRP [r = 0.442, p = 0.0001; r = 0.243, p = 0.009, respectively]Our study demonstrates that serum hepcidin is increased in IBD children with active disease and it is responsible for IM.

Pachydermoperiostosis (PDP), otherwise known as primary hypertrophic osteoarthropathy, is characterized by digital clubbing, pachydermia and subperiosteal new bone formation. Joint pain, polyarthritis, cutis verticis gyrata, seborrhea, and hyperhidrosis are frequently associated to this condition. We report a 17-year-old boy presented with pain and swelling of knees and ankles, and progressive thickening of skin face with seborrhea from about 4 years. At the admission he also showed digital clubbing of both hands and feet and palmoplantar hyperhidrosis. We hypothesized PDP and molecular analysis confirmed diagnosis showing a novel mutation in a homozygous state in the SLCO2A1 gene coding for prostaglandin transporter. He started therapy with hydroxychloroquine with a great improvement in joint pain and skin conditions. This is the first reported case of PDP who was successfully treated with hydroxychloroquine, with effects not only on arthralgia but also, surprisingly, on skin conditions.

Hiatal hernia (HH) affects from 10% to 50% of adult population. The correlation between HH, gastroesophageal reflux disease, dyspeptic symptoms, and esophagitis has long been known in adults. The primary objective of our prospective observational study was to estimate the prevalence of HH in children undergoing esophagogastroduodenoscopy (EGD), irrespective of their symptoms. METHODS: We prospectively enrolled 111 consecutive children (48 boys and 63 girls; mean age 94.9 ± 52.3 months) referred for EGD. In all of the patients a asymptomatic score assessment based on the Rome III criteria was used to measure frequency, severity, and duration of gastrointestinal symptoms. HH presence was endoscopically defined; esophagitis presence was evaluated either endoscopically and histologically. Children were divided in 2 age-range groups: 48 months (group 2). RESULTS: Twenty-three patients of 111 (20.7%) had evidence of a sliding HH at EGD. In children from group 2, we found a statistically significant association of HH with heartburn (P = 0.03, 95% confidence interval 1-9.3, r = 0.1) and regurgitation (P = 0.003, 95% confidence interval 1.7-20.4, r = 0.3). Regarding esophagitis presence, no association was found at any age either with defined esophagitis or with dilated intercellular spaces. CONCLUSIONS: Prevalence of HH in our study population was 20.7%. According to our data, HH correlates with the presence of heartburn and regurgitation in children, but not in toddlers. No association was found with esophagitis at any age.

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).

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).

BACKGROUND AND AIMS: There are only few case reports describing the frequency and the clinical features of pancreatic involvement (PI) in inflammatory bowel disease (IBD). We aimed to estimate the prevalence and to characterize IBD pediatric patients with PI. METHODS: We retrospectively reviewed data collected in the IBD web-registry of the Italian Society for Pediatric Gastroenterology, Hepatology and Nutrition. All children presenting with hyperamylasemia and/or hyperlipasemia were identified. Demographic and clinical data, IBD type, disease exstension and activity, laboratory data, IBD therapy, imaging findings and therapeutic interventions were evaluated. Acute pancreatitis (AP) was defined by the occurrence of at least two of the following findings: acute epigastric abdominal pain, elevated serum amylase and/or lipase ≥ 3 times the upper level of normal, and characteristic radiological changes. RESULTS: We found 27 children out of 649 (4.1%) with an increased value of amylase and/or lipase [Median Age: 148, range 65-191, mths; F/M: 14/13; Ulcerative colitis (UC): 12; Crohn's disease (CD): 13; Unclassified Colitis (IBDU): 2)]. Mean serum amylase level was 205.3 ± 91.5 (range 61-413 IU/L) and mean serum lipase level was 526.8 ± 598.8 (range 37-2565 IU/L). Eleven patients (1.6%) fulfilled diagnostic criteria for AP (6 CD, 4 UC, 1 IBDU). Ten (37%) patients underwent imaging ultrasound scan, 8 (29.6%) patients had magnetic resonance cholangiopancreatography and 2 (7.4%) patients had a computed tomography scan. Pancreatic pathological findings were found in all subjects with AP. The mean lag time period between the diagnosis of IBD and the PI was 12.1 mths (range 0-65). Five patients out of 27 (18.5%) showed PI at diagnosis of IBD. Twenty-four out of 27 (88.8%) had colonic disease [10 CD, 12 UC (8 pancolitis) and 2 IBDU]. Ten patients were receiving mesalamine (ASA) and 16 patients were under immunosuppressive therapy [3 streoids, 6 azathioprine (AZT), 5 AZT + ASA, 1 methotrexate, 1 infliximab (IFX), and 1 IFX+ASA+AZT], while 1 patient was not treated. Comparing with the patients with an exclusive hyperamylasemia and/or hyperlipasemia, AP was significantly associated with female gender (p=0.018), whereas type of IBD, ongoing treatments, activity and extension of disease did not result significant risk factors. Seven out of 11 (63.6%) patients with AP needed therapeutic measures including AZT and/or ASA withdrawal, compared to only 4 (25%) patients out of 16 with serum hyperamylasemia and/or hyperlipasemia (p=0.06). CONCLUSIONS: Our study suggests that prevalence of AP in children is similar to that reported in adults. PI was more common in colonic disease. Female gender seems to be a risk factor for developing AP in children. In contrast to previous study, PI was not associated with any type of IBD.

severe disease activity decreased from 31% to 6% and has been consistently below 10% over the last year. Mild disease activity also decreased from 23% to 16%. Overall remission increased from 46% to 78%. Conclusion: We demonstrated dramatic reduction of moderate to severe disease activity since joining the ICN collaboration due to a timely intervention based on readily available live data reporting. ICN is an excellent tool for improving the quality of care of our patients, managing their treatment and improving their outcomes.