Scientific evidence for the treatment of children with irritable bowel syndrome

Irritable bowel syndrome (IBS) is the commonest cause of recurrent abdominal pain in children in both more developed and developing parts of the world. It is characterized by abdominal pain that is improved by defecation and whose onset is associated with a change in stool form and/or frequency and is not explained by structural or biochemical abnormalities. A number of potential patho-physiological mechanisms have been described, but so far the exact underlying etiology of IBS is unclear. Likewise, no optimal treatment has ever been found neither for adult nor for pediatric patients. Current therapeutic options include drugs, dietary interventions and biopsychosocial therapies. The present review aims at evaluating the scientific evidence supporting the efficacy of these treatments for children with IBS

MMP-9 as a Candidate Marker of Response to BRAF Inhibitors in Melanoma Patients With BRAFV600E Mutation Detected in Circulating-Free DNA

The BRAFV600E mutation is associated with melanoma development and its detection in circulating-free DNA cannot be observed in all melanoma patients harboring this mutation in tumor specimens. Beside the circulating-free DNA BRAFV600E mutation, other markers of therapeutic response should be identified. Matrix metalloproteinase-9 (MMP-9) could be one of them as its role as indicator of invasiveness in melanoma have been explored. In this study, MMP-9 was evaluated in melanoma cells after treatment with dabrafenib. In vitro data were validated in 26 melanoma patients, of which 14 treated with BRAF inhibitor alone and 12 treated with both BRAF and MEK inhibitors, by ELISA assay and droplet digital PCR for measuring MMP-9 serum levels and circulating-free DNA BRAFV600E mutation, respectively. Statistical analyses were performed to evaluate the prognostic significance of MMP-9, progression-free survival (PFS) and overall survival (OS) according to the BRAFV600E mutation and MMP-9 levels. The performed analyses showed that MMP-9 and pEKR1-2 were statistically down-regulated in melanoma cells after treatment with dabrafenib. Circulating-free DNA BRAFV600E mutation was detected in 11 out of 26 melanoma patients showing higher levels of MMP-9 compared to those with undetectable BRAFV600E mutation. Furthermore, higher levels of MMP-9 and circulating-free DNA BRAFV600E mutation were associated with lower PFS and OS. Finally, the monitoring of therapy showed that MMP-9 significantly decreased at T1 and T2, but not at T-last, for the patients with detectable circulating-free DNA BRAFV600E mutation. In conclusion, high levels of MMP-9 and circulating-free DNA BRAFV600E mutation are associated with poor PFS and OS. MMP-9 may represent a promising indicator of response to BRAF inhibitors in combination with the detection of BRAFV600E mutation

Assessment of respiratory function in infants and young children wearing face masks during the COVID-19 pandemic

Importance: Face masks have been associated with effective prevention of diffusion of viruses via droplets. However, the use of face masks among children, especially those aged younger than 3 years, is debated, and the US Centers for Disease Control and American Academy of Physicians recommend the use of face mask only among individuals aged 3 years or older.Objective: To examine whether the use of surgical facial masks among children is associated with episodes of oxygen desaturation or respiratory distress.Design, Setting, and Participants: This cohort study was conducted from May through June 2020 in a secondary-level hospital pediatric unit in Italy. Included participants were 47 healthy children divided by age (ie, group A, aged ≤24 months, and group B, aged >24 months to ≤144 months). Data were analyzed from May through June 2020.Interventions: All participants were monitored every 15 minutes for changes in respiratory parameters for the first 30 minutes while not wearing a surgical face mask and for the next 30 minutes while wearing a face mask. Children aged 24 months and older then participated in a walking test for 12 minutes.Main Outcomes and Measures: Changes in respiratory parameters during the use of surgical masks were evaluated.Results: Among 47 children, 22 children (46.8%) were aged 24 months or younger (ie, group A), with 11 boys (50.0%) and median (interquartile range [IQR]) age 12.5 (10.0-17.5) months, and 25 children (53.2%) were aged older than 24 months to 144 months or younger, with 13 boys (52.0%) and median (IQR) age 100.0 (72.0-120.0) months. During the first 60 minutes of evaluation in the 2 groups, there was no significant change in group A in median (IQR) partial pressure of end-tidal carbon dioxide (Petco2; 33.0 [32.0-34.0] mm Hg; P for Kruskal Wallis =.59), oxygen saturation (Sao2; 98.0% [97.0%-99.0%]; P for Kruskal Wallis =.61), pulse rate (PR; 130.0 [115.0-140.0] pulsations/min; P for Kruskal Wallis =.99), or respiratory rate (RR; 30.0 [28.0-33.0] breaths/min; P for Kruskal Wallis =.69) or for group B in median (IQR) Petco2 (36.0 [34.0-38.0] mm Hg; P for Kruskal Wallis =.97), Sao2 (98.0% [97.0%-98.0%]; P for Kruskal Wallis =.52), PR (96.0 [84.0-104.5] pulsations/min; P for Kruskal Wallis test=.48), or RR (22.0 [20.0-25.0] breaths/min; P for Kruskal Wallis =.55). After the group B walking test, compared with before the walking test, there was a significant increase in median (IQR) PR (96.0 [84.0-104.5] pulsations/min vs 105.0 [100.0-115.0] pulsations/min; P<.02) and RR (22.0 [20.0-25.0] breaths/min vs 26.0 [24.0-29.0] breaths/min; P<.05).Conclusions and Relevance: This cohort study among infants and young children in Italy found that the use of facial masks was not associated with significant changes in Sao2 or Petco2, including among children aged 24 months and younger

Cyclic Vomiting Syndrome in Children

Cyclic Vomiting Syndrome (CVS) is an underdiagnosed episodic syndrome characterized by frequent hospitalizations, multiple comorbidities, and poor quality of life. It is often misdiagnosed due to the unappreciated pattern of recurrence and lack of confirmatory testing. CVS mainly occurs in pre-school or early school-age, but infants and elderly onset have been also described. The etiopathogenesis is largely unknown, but it is likely to be multifactorial. Recent evidence suggests that aberrant brain-gut pathways, mitochondrial enzymopathies, gastrointestinal motility disorders, calcium channel abnormalities, and hyperactivity of the hypothalamic-pituitary-adrenal axis in response to a triggering environmental stimulus are involved. CVS is characterized by acute, stereotyped and recurrent episodes of intense nausea and incoercible vomiting with predictable periodicity and return to baseline health between episodes. A distinction with other differential diagnoses is a challenge for clinicians. Although extensive and invasive investigations should be avoided, baseline testing toward identifying organic causes is recommended in all children with CVS. The management of CVS requires an individually tailored therapy Management of acute phase is mainly based on supportive and symptomatic care. Early intervention with abortive agents during the brief prodromal phase can be used to attempt to terminate the attack. During the interictal period, non-pharmacologic measures as lifestyle changes and the use of reassurance and anticipatory guidance seem to be effective as a preventive treatment. The indication for prophylactic pharmacotherapy depends on attack intensity and severity, the impairment of the QoL and if attack treatments are ineffective or cause side effects. When children remain refractory to acute or prophylactic treatment, or the episode differs from previous ones, the clinician should consider the possibility of an underlying disease and further mono- or combination therapy and psychotherapy can be guided by accompanying comorbidities and specific sub-phenotype. This review was developed by a joint task force of the Italian Society of Pediatric Gastroenterology Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP) to identify relevant current issues and to propose future research directions on pediatric CV

Faecal high mobility group box 1 in children with celiac disease: A pilot study

Background: Celiac disease (CD) is a gluten-related immunological disorder resulting in inflammatory enteropathy. Aims: We assessed a stool marker of intestinal inflammation, the HMGB1 protein, in children with CD on a gluten free diet (GFD) at baseline and at follow up (FU). Methods: Thirty-nine children were investigated at diagnosis and at FU. Traditional serum markers of CD (anti-transglutaminase and anti-endomysial antibodies) and faecal HMGB1 (by enzyme-linked immunosorbent assay and immunoblotting) were tested. Results: There was a marked increase at baseline in both serum anti-transglutaminase IgA (anti-tTGAs) and faecal HMGB1; the latter being undetectable in controls. A strong correlation occurred between the two markers. At 12-month FU in 24 patients on GFD, HMGB1 decreased in all subjects, yet still being detectable in six children: high anti-tTGAs where evident in three, while the three with normal anti-tTGAs were complaining of intestinal symptoms and reported a low GFD adherence. Conclusions: Faecal HMGB1 is a valuable marker of intestinal inflammation and may have a role in complementing serology in the management of CD children. Future studies including larger patient cohorts and small bowel mucosa histology will be designed to assess the relationship between faecal HMGB1 levels and duodeno-jejunal histopathology

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). Aim To assess in children with active distal UC the effectiveness of Lactobacillus (L) reuteri ATCC 55730 enema on inflammation and cytokine expression of rectal mucosa. Methods A total of 40 patients (median age: 7.2 years range 6-18) with mild to moderate UC were enrolled in a prospective, randomised, placebo-controlled study. They received an enema solution containing 10(10) CFU of L. reuteri ATCC 55730 or placebo for 8 weeks, in addition to oral mesalazine. Clinical endoscopic and histological scores as well as rectal mucosal expression levels of IL-10, IL-1 beta, TNF alpha and IL-8 were evaluated at the beginning and at the end of the trial. Results Thirty-one patients accomplished the trial (17 males, median age 13 year, range 7-18). Mayo score (including clinical and endoscopic features) decreased significantly in the L. reuteri group (3.2 +/- 1.3 vs. 8.6 +/- 0.8, P < 0.01) compared with placebo (7.1 +/- 1.1 vs. 8.7 +/- 0.7, NS); furthermore, histological score significantly decrease only in the L. reuteri group (0.6 +/- 0.5 vs. 4.5 +/- 0.6, P < 0.01) (placebo: 2.9 +/- 0.8 vs. 4.6 +/- 0.6, NS). At the post-trial evaluation of cytokine mucosal expression levels, IL-10 significantly increased (P < 0.01) whereas IL-1 beta, TNF alpha and IL-8 significantly decreased (P < 0.01) only in the L. reuteri group. Conclusions In children with active distal ulcerative colitis, rectal infusion of L. reuteri is effective in improving mucosal inflammation and changing mucosal expression levels of some cytokines involved in the mechanisms of inflammatory bowel disease

Efficacy and tolerability of \u3b1-galactosidase in treating gas-related symptoms in children: a randomized, double-blind, placebo controlled trial

BACKGROUND: Gas-related symptoms represent very common complaints in children. The reduction of gas production can be considered as a valuable target in controlling symptoms. \u3b1-galactosidase has been shown to reduce gas production and related symptoms in adults. To evaluate the efficacy and tolerability of \u3b1-galactosidase in the treatment of gas-related symptoms in pediatric patients. METHODS: Single center, randomized, double-blind, placebo-controlled, parallel group study performed in tertiary care setting. Fifty-two pediatric patients (32 female, age range 4-17) with chronic or recurrent gas-related symptoms were randomized to receive placebo (n\u2009=\u200925) or \u3b1-galactosidase (n\u2009=\u200927). Both treatments were given as drops or tablets, according to body weight for 2 weeks. The primary endpoint was the reduction in global distress measured by the Faces Pain Scale-Revised (FPS-R) at the end of treatment compared to baseline. Secondary endpoints were the reduction in severity and frequency of gas-related symptoms as recorded by parents and/or children. RESULTS: \u3b1-galactosidase significantly reduced global distress (p\u2009=\u20090.02) compared to placebo. The digestive enzyme decreased the number of days with moderate to severe bloating (p\u2009=\u20090.03) and the proportion of patients with flatulence (p\u2009=\u20090.02). No significant differences were found for abdominal spasms and abdominal distension. No adverse events were reported during treatment. CONCLUSIONS: Although larger and longer trials are needed to confirm this result, \u3b1-galactosidase seems to be a safe, well tolerated and effective treatment for gas-related symptoms in the pediatric population

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. Copyright © 2012 by the American Society for Gastrointestinal Endoscopy