Malignancy and mortality in paediatric-onset inflammatory bowel disease: a 3-year prospective, multinational study from the paediatric IBD Porto group of ESPGHAN.

BACKGROUND: Risk benefit strategies in managing inflammatory bowel diseases (IBD) are dependent upon understanding the risks of uncontrolled inflammation vs those of treatments. Malignancy and mortality in IBD have been associated with disease-related inflammation and immune suppression, but data are limited due to their rare occurrence. AIM: To identify and describe the most common causes of mortality, types of cancer and previous or current therapy among children and young adults with paediatric-onset IBD. METHODS: Information on paediatric-onset IBD patients diagnosed with malignancy or mortality was prospectively collected via a survey in 25 countries over a 42-month period. Patients were included if death or malignancy occurred after IBD diagnosis but before the age of 26 years. RESULTS: In total, 60 patients were identified including 43 malignancies and 26 fatal cases (9 due to cancer). Main causes of fatality were malignancies (n = 9), IBD or IBD-therapy related nonmalignant causes (n = 10; including 5 infections), and suicides (n = 3). Three cases, all fatal, of hepatosplenic T-cell lymphoma were identified, all were biologic-naïve but thiopurine-exposed. No other haematological malignancies were fatal. The 6 other fatal cancer cases included 3 colorectal adenocarcinomas and 3 cholangiocarcinomas (CCAs). Primary sclerosing cholangitis (PSC) was present in 5 (56%) fatal cancers (1 colorectal carcinoma, 3 CCAs and 1 hepatosplenic T-cell lymphoma). CONCLUSIONS: We report the largest number of paediatric-onset IBD patients with cancer and/or fatal outcomes to date. Malignancies followed by infections were the major causes of mortality. We identified PSC as a significant risk factor for cancer-associated mortality. Disease-related adenocarcinomas were a commoner cause of death than lymphomas.

European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European Academy of Neurology

BACKGROUND AND PURPOSE: Current guidelines on cerebral venous thrombosis (CVT) diagnosis and management were issued by the European Federation of Neurological Societies in 2010. We aimed to update the previous European Federation of Neurological Societies guidelines using a clearer and evidence-based methodology. METHOD: We followed the Grading of Recommendations, Assessment, Development and Evaluation system, formulating relevant diagnostic and treatment questions, performing systematic reviews and writing recommendations based on the quality of available scientific evidence. RESULTS: We suggest using magnetic resonance or computed tomographic angiography for confirming the diagnosis of CVT and not routinely screening patients with CVT for thrombophilia or cancer. We recommend parenteral anticoagulation in acute CVT and decompressive surgery to prevent death due to brain herniation. We suggest preferentially using low-molecular-weight heparin in the acute phase and not direct oral anticoagulants. We suggest not using steroids and acetazolamide to reduce death or dependency. We suggest using antiepileptics in patients with an early seizure and supratentorial lesions to prevent further early seizures. We could not make recommendations concerning duration of anticoagulation after the acute phase, thrombolysis and/or thrombectomy, therapeutic lumbar puncture, and prevention of remote seizures with antiepileptic drugs. We suggest that, in women who have suffered a previous CVT, contraceptives containing oestrogens should be avoided. We suggest that subsequent pregnancies are safe, but use of prophylactic low-molecular-weight heparin should be considered throughout pregnancy and puerperium. CONCLUSIONS: Multicentre observational and experimental studies are needed to increase the level of evidence supporting recommendations on the diagnosis and management of CVT.

The knowledge and expectations about IBD - difference between pediatric patients and their parents.

BACKGROUND AND STUDY AIMS: The aim of this prospective survey was to determine and compare the knowledge of children with inflammatory bowel disease (IBD) and their parents about their disease. Furthermore, patients and parents were ask to provide the main source for disease related information and to give opinion for possible improvement. PATIENTS AND METHODS: This was a prospective survey which included children with IBD with ≥ 12 years of age and their parents. Only ambulatory patients treated in tertiary medical center were included. RESULTS: 38 child/parent pairs (79% mothers) were enrolled. Major differences between parents and children were in a) internet search where majority of parents (n = 28 ; 73.7%) and only 17 (44.7%) children gathered disease related information over the internet (p = 0.01) ; b) need for participation in patients' organization (97.4% parents comparing 55.3% children would like to participate ; p<0.001) and c) clinical practice with time reserved for child/adolescent to be with his/her physician alone (78.9% of parents encourage this practice comparing to 2.6% of children ; p <0.001). CONCLUSION: This study shows significant difference between children/adolescents with IBD and their parents in several aspects that should be acknowledged before initiating changes into the clinical practice.

The importance of combined 24-hour multichannel intraluminal impedance-pH monitoring in the evaluation of children with suspected laryngopharyngeal reflux.

OBJECTIVE: The aim of this study was to investigate the diagnostic usefulness of combined multichannel intraluminal impedance-pH (MII-pH) monitoring in children with suspected laryngopharyngeal reflux (LPR). DESIGN, SETTING AND PARTICIPANTS: A prospective study including children in whom, due to LPR suggestive symptoms, MII-pH monitoring was performed at tertiary medical centre from February 2012 to July 2015. INTERVENTIONS: All included children underwent same diagnostic protocol which included examination by single pulmonologist and ENT specialist and underwent 24-hour MII-pH monitoring. MAIN OUTCOMES: Primary outcome was to determine MII-pH characteristics of the children in whom LPR was suspected based on symptoms and ENT examination. RESULTS: One hundred and four patients (mean age 8.9 years; range 0.4-17.9 years; male/female 57/47) participated in the study. In children with signs and symptoms suggestive of LPR, MII-pH monitoring found the median incidence of proximal gastro-oesophageal reflux (GER) of 15 (range 0-129), proximal acidic GER of 6.5 (range 0-66) and weakly acidic GER of 5 (range 0-102). There were significant positive correlations between the number of GER (proximal total, acidic and weakly acid) with Reflux Finding Score, Reflux Symptom Index and presence of eosinophils in nasal swabs. The only endoscopy ENT finding which significantly correlated with total proximal GER, acid proximal GER and weakly acidic proximal GER was arytenoid hyperaemia. CONCLUSION: Both acid and non-acid reflux seem to have a significant role in the pathogenesis of LPR.

The role of combined 24-h multichannel intraluminal impedance-pH monitoring in the evaluation of children with gastrointestinal symptoms suggesting gastro-esophageal reflux disease.

BACKGROUND: The aim of this study was to determine the role of multichannel intraluminal impedance-pH (pH-MII) monitoring in the diagnosis of gastro-esophageal reflux disease (GERD) in children who presented with gastrointestinal (GI) symptoms in comparison with the results of pH-metry alone and endoscopy. METHODS: All children who underwent pH-MII monitoring due to GI symptoms, suggestive of GERD, from October 2013 to October 2015 in Children's Hospital Zagreb, were retrospectively enrolled in the study. The cohort was divided into three groups according to age - group 1: children <1 year of age; group 2: 1-9 years of age; and group 3: ≥9 years of age. KEY RESULTS: One hundred thirty-three patients met our inclusion criteria (73 female/60 male; mean age 9.2 years [0.19-18.0]). Gastro-esophageal reflux disease was determined in 44 of 133 patients (33.1%) by pH-MII and only in 21 of 133 patients (15.8%) by pH-metry alone. Endoscopy was performed in 77 (57.9%) children and esophagitis was found in 32/77 (41.6%). The finding of esophagitis significantly correlated with the number of total reflux episodes (coef. 0.42, p < 0.001), acidic (coef. 0.26, p = 0.02), weakly acidic (coef. 0.3, p = 0.008) and non-acidic (coef. 0.26, p = 0.02) reflux episodes detected by pH-MII; but, no correlation was found to reflux episodes detected by pH-metry alone (coef. 0.21, p = 0.07). CONCLUSIONS & INFERENCES: Compared with pH-metry alone, pH-MII performed significantly better in the detection of GERD in all age groups. On the basis of our data, pH-MII had a strong correlation with endoscopically confirmed esophagitis.

Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics

The use of probiotics has been suggested in the treatment of acute gastroenteritis (AGE) in addition to early rehydration and avoidance of dietary restrictions. This document provides recommendations for the use of probiotics for the treatment of AGE in previously healthy infants and children based on a systematic review of previously completed systematic reviews and of randomized controlled trials (RCTs) published subsequently to these reviews. The recommendations were formulated only if at least 2 RCTs that used a given probiotic (with strain specification) were available. The GRADE system developed by the Grading of Recommendations, Assessment, Development, and Evaluations Working Group, was used to grade the strength of evidence and grades of recommendations used in these guidelines. It offers 4 categories of the quality of the evidence (high, moderate, low, and very low) and 2 categories of the strength of recommendation (strong or weak). The use of the following probiotics (in alphabetical order) may be considered in the management of children with AGE in addition to rehydration therapy: Lactobacillus rhamnosus GG (low quality of evidence, strong recommendation) and Saccharomyces boulardii (low quality of evidence, strong recommendation). Less compelling evidence is available for Lactobacillus reuteri DSM 17938 (very low quality of evidence, weak recommendation) and heat-inactivated Lactobacillus acidophilus LB (very low quality of evidence, weak recommendation). The latter, although traditionally discussed with other probiotics, does not fit with the definition of probiotics. Other strains or combinations of strains have been tested, but evidence of their efficacy is weak or preliminary.

Tissue transglutaminase antibodies in celiac disease: focus on the pediatric population.

Celiac disease (CD) is an immune-mediated disorder induced by the ingestion of gluten in genetically susceptible individuals. The enzyme tissue transglutaminase (protein-glutamine gamma-glutamyltransferase 2; tTG) plays an important role in the pathogenesis of the disease and antibodies against tTG are used as serological markers for the diagnosis of CD. Discovery of tTG as the autoantigen for endomysial antibodies changed the diagnostic approach to patients with suspected CD and, importantly, made screening for CD more accurate and easier to perform. Studies in pediatric populations confirmed the high sensitivity and specificity of immunoglobulin A (IgA) tTG antibodies in the diagnosis of CD. The aim of this review is to summarize the data on the role of tTG in the pathogenesis of CD and to present current evidence on the accuracy of IgA tTG, IgG tTG and IgA tTG point-of-care tests in the diagnosis of CD in children. This review shows why IgA tTG antibodies replaced endomysial antibodies as the preferred serological marker due to the ease of their use, their high sensitivity and specificity, and the high correlation between high titers and intestinal mucosal lesions.