Innovative Makeshift Technique for Removing Ingested Rare Earth Magnets

Swallowing foreign bodies is common in pediatrics. However, ingestion of rare earth magnets, composed of a neodymium alloy with powerful attractive forces, pose unique risks to children. The attraction of the magnets to each other when positioned in separate areas of the intestinal tract can lead to bowel obstruction, perforation, fistula formation, or pressure necrosis. These significant complications have led NASPGHAN to offer guidance for their urgent removal in children. Upon medical presentation and determination of their position on x-ray, ingested magnets should be removed urgently before entering the small intestine to prevent severe adverse events.1,2 However, endoscopic location and removal can be challenging especially if the child has not been in a fasting state. We present a makeshift technique for easily removing magnetic foreign bodies in such a scenario

Molecular and Histological Profiling Reveals an Innate-Shaped Immune Microenvironment in Solitary Juvenile Polyps.

INTRODUCTION Solitary juvenile polyps (JP) are characterized by a benign disease course with low recurrence rate but present with signs of intestinal inflammation. To better understand the underlying pathogenesis, we performed histological and molecular evaluation targeting distinct immune mechanisms. METHODS Pediatric patients with JP (n = 12), with treatment-naïve inflammatory bowel disease (IBD; [n = 41]) as inflammatory control, and non-IBD controls (n = 14) were investigated. For a comparative analysis of infiltrating immune cells, a next-generation tissue microarray of biopsies was assembled, immunostained, and scored. Targeted transcriptional profiling was performed using a customized immunology panel. RESULTS In JP, a predominant accumulation of neutrophils and eosinophils was observed. RNA expression profiles revealed increased levels of CXCL8, CXCL5, and CCL11 transcripts in JP, indicating an enhanced recruitment of neutrophils and eosinophils. Moreover, messenger RNA levels of the proinflammatory cytokine IL1b and the inflammation-amplifying receptor TREM1 were higher in JP, whereas we could not find signs of a functionally polarized Tcell response in JP when compared with IBD. DISCUSSION Patients with JP and patients with treatment-naïve IBD have distinct cell infiltrates during active disease. The ample presence of eosinophils in JP supports neutrophil accumulation, which is responsible for the elevated release of calprotectin. Intriguingly, however, we were not able to identify a functionally polarized T-cell response in JP, which indicates that during the acute onset of inflammation in JP, a potent adaptive immune memory is not established. This may explain the low reoccurrence rate of JP

Drug-related adverse events necessitating treatment discontinuation in pediatric inflammatory bowel disease patients.

BACKGROUND AND AIMS Inflammatory bowel disease (IBD) requires long-term drug therapy in most patients, posing a risk for adverse drug events with the need for discontinuation. In this study, we investigated adverse events (AE) necessitating drug discontinuation in pediatric and adolescent IBD patients. METHODS We used data prospectively collected from IBD patients below the age of 18 enrolled in the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS), namely demographic variables, medical characteristics, drug treatments and related AE. We analysed the frequency, type, and risk factors for AE necessitating drug discontinuation. RESULTS A total of 509 pediatric IBD patients fulfilled the inclusion criteria of which 262 (51.5%) were diagnosed with Crohn's disease (CD), 206 (40.5%) with ulcerative colitis (UC), and 41 (8%) with IBD-unclassified (IBD-U). In total, 132 (25.9%) presented with at least one drug-related AE that required drug cessation. Immunomodulators (methotrexate 29/120 (24.2%), azathioprine 57/372 (15.3%)) followed by tumor necrosis factor (TNF)-alpha antagonists (adalimumab 8/72 (11.1%), infliximab 22/227 (9.7%)) accounted for the highest proportions of AE necessitating treatment discontinuation. Treatment schemes with at least 3 concomitant drugs significantly amplified the risk for development of drug-related AE (OR = 2.50, 95%CI [1.50-4.17]) in all pediatric IBD patients. CONCLUSIONS Drug-related AE necessitating discontinuation are common in pediatric and adolescent inflammatory bowel disease patients. Caution needs to be taken in the case of concomitant drug use

The Use of 5-Aminosalicylic Acid in Children and Adolescents With Inflammatory Bowel Disease

BACKGROUND In ulcerative colitis (UC) 5-aminosalicylic acid (5-ASA) is recommended as primary therapy for mild to moderate disease. Topical 5-ASA has been proven especially effective. In Crohn's disease (CD) the evidence for a beneficial role of 5-ASA is weak. We investigated the use of topical and systemic 5-ASA therapy in children and adolescents with inflammatory bowel disease. MATERIALS AND METHODS Data of patients younger than 18 years, registered between April 2008 and December 2015 in the Swiss Inflammatory Bowel Disease Cohort, were analyzed. RESULTS Three hundred twenty pediatric inflammatory bowel disease patients were included; 189 with CD and 131 with UC. Over one third of UC patients [51 (39%)] received topical 5-ASA therapy and 43 (33%) received combination therapy during their disease course. UC patients with left-sided colitis or proctitis were more likely to receive topical or combination therapy as compared with patients with pancolitis (P<0.001 and <0.001, respectively). An increase in the use of topical 5-ASA therapy in UC patients was noted over time from 5% to 38%. Forty-seven percent of CD patients were treated with oral 5-ASA during their disease course. The usage was stable over time at approximately 15% to 20%. CONCLUSIONS In recent years a very positive trend showing an increase in topical 5-ASA therapy in children and adolescents with UC has been observed. However topical therapy is still used with relative low frequency, especially in patients with a more extensive disease. Conversely, despite weak evidence supporting 5-ASA use in CD patients it has been frequently prescribed. Physicians should continue to encourage their UC patients to use topical therapy

Impact of Diagnostic Delay on Disease Course in Pediatric- versus Adult-Onset Patients with Ulcerative Colitis: Data from the Swiss IBD Cohort

INTRODUCTION Given the lack of data, we aimed to assess the impact of the length of diagnostic delay on the natural history of ulcerative colitis (UC) in pediatric (diagnosed <18 years) and adult patients (diagnosed ≥18 years). METHODS Data from the Swiss Inflammatory Bowel Disease Cohort Study were analyzed. Diagnostic delay was defined as the interval between the first appearance of UC-related symptoms until diagnosis. Logistic regression modeling evaluated the appearance of the following complications in the long term according to the length of diagnostic delay: colonic dysplasia, colorectal cancer, UC-related hospitalization, colectomy, and extraintestinal manifestations (EIMs). RESULTS A total of 184 pediatric and 846 adult patients were included. The median diagnostic delay was 4 [IQR 2-7.5] months for the pediatric-onset group and 3 [IQR 2-10] months for the adult-onset group (p = 0.873). In both, pediatric- and adult-onset groups, the length of diagnostic delay at UC diagnosis was not associated with colectomy, UC-related hospitalization, colon dysplasia, and colorectal cancer. EIMs were significantly more prevalent at UC diagnosis in the adult-onset group with long diagnostic delay than in the adult-onset group with short diagnostic delay (p = 0.022). In the long term, the length of diagnostic delay was associated in the adult-onset group with colorectal dysplasia (p = 0.023), EIMs (p < 0.001), and more specifically arthritis/arthralgias (p < 0.001) and ankylosing spondylitis/sacroiliitis (p < 0.001). In the pediatric-onset UC group, the length of diagnostic delay in the long term was associated with arthritis/arthralgias (p = 0.017); however, it was not predictive for colectomy and UC-related hospitalization. CONCLUSIONS As colorectal cancer and EIMs are associated with considerable morbidity and costs, every effort should be made to reduce diagnostic delay in UC patients

Slit2 prevents neutrophil recruitment and renal ischemia-reperfusion injury

Neutrophils recruited to the postischemic kidney contribute to the pathogenesis of ischemia-reperfusion injury (IRI), which is the most common cause of renal failure among hospitalized patients. The Slit family of secreted proteins inhibits chemotaxis of leukocytes by preventing activation of Rho-family GTPases, suggesting that members of this family might modulate the recruitment of neutrophils and the resulting IRI. Here, in static and microfluidic shear assays, Slit2 inhibited multiple steps required for the infiltration of neutrophils into tissue. Specifically, Slit2 blocked the capture and firm adhesion of human neutrophils to inflamed vascular endothelial barriers as well as their subsequent transmigration. To examine whether these observations were relevant to renal IRI, we administered Slit2 to mice before bilateral clamping of the renal pedicles. Assessed at 18 hours after reperfusion, Slit2 significantly inhibited renal tubular necrosis, neutrophil and macrophage infiltration, and rise in plasma creatinine. In vitro, Slit2 did not impair the protective functions of neutrophils, including phagocytosis and superoxide production, and did not inhibit neutrophils from killing the extracellular pathogen Staphylococcus aureus. In vivo, administration of Slit2 did not attenuate neutrophil recruitment or bacterial clearance in mice with ascending Escherichia coli urinary tract infections and did not increase the bacterial load in the livers of mice infected with the intracellular pathogen Listeriamonocytogenes. Collectively, these results suggest that Slit2 may hold promise as a strategy to combat renal IRI without compromising the protective innate immune response. Copyright © 2013 by the American Society of Nephrology

Differences in management of eosinophilic esophagitis in Europe : an assessment of current practice

Objectives:The aim of the study was to assess differences in the diagnosis and management of eosinophilic esophagitis (EoE) by European pediatric (PG) and adult gastroenterologists (AG), and their self-reported adherence to guidelines. Methods:A multiple-choice questionnaire gauged the diagnostic and management strategies of gastroenterologists treating children or adults in 14 European countries and the United Arab Emirates (UAE). Results:Questionnaires were completed by 465 PG and 743 AG. PG were significantly more likely to take biopsies in patients with symptoms of esophageal dysfunction (86.2% PG vs 75.4% AG, P<0.001) and to perform endoscopic follow-up (86.3% PG vs 80.6% AG, P<0.001). After failure of proton-pump inhibitors (PPIs), topical steroids were the preferred second-line therapy; however, PG opted more frequently for elimination diets (47.5% PG vs 13.7% AG, P<0.001). More PG than AG indicated having read recent guidelines (89.4% PG vs 58.2% AG, P<0.001). Geographic differences in practice were reported, with respondents from the United Kingdom, Portugal, and Spain more often adhering to recommended biopsy protocols. Physicians in the UAE, France, Lithuania, and Poland tended to opt for steroid therapy or elimination diets as first-line therapy, in contrast to most other countries. Conclusions:Significant differences in general practice between PG and AG were demonstrated with notable divergence from consensus guidelines. International practice variations are also apparent. Among other strategies, educational activities to highlight current recommendations may help harmonize and optimize clinical practice

Therapeutische Diäten bei Morbus Crohn

Die exklusive enterale Ernährungstherapie (EEN) ist eine etablierte Behandlung bei Kindern und Jugendlichen mit einer chronisch-entzündlichen Darmerkrankung (CED). Die eingeschränkte Alltagstauglichkeit erschwert insbesondere bei Erwachsenen die Compliance. Neue diätische Ansätze bieten eine vielversprechende Alternative zur klassischen EEN