Extraintestinal Manifestations of Pediatric Inflammatory Bowel Disease: Prevalence, Presentation, and Anti-TNF Treatment.

There is a paucity of data on extraintestinal manifestations (EIM) and their treatment in pediatric patients with inflammatory bowel disease (IBD). Since 2008, the Pediatric Swiss IBD Cohort Study has collected data on the pediatric IBD population in Switzerland. Data on 329 patients were analyzed retrospectively. A total of 55 patients (16.7%) experienced 1-4 EIM (39 Crohn disease, 12 ulcerative colitis, and 4 IBD-unclassified patients). At IBD onset, presence of EIM was more frequent than in the adult population (8.5% vs 5.0%, P = 0.014). EIM were more frequent in Crohn disease when compared to ulcerative colitis/IBD-unclassified (22.5% vs 10.3%, P = 0.003). The most prevalent EIM were peripheral arthritis (26/329, 7.9%) and aphthous stomatitis (24/329, 7.3%). Approximately 27.6% of all EIM appeared before IBD diagnosis. Median time between IBD diagnosis and occurrence of first EIM was 1 month (-37.5-149.0). Thirty-one of the 55 patients (56.4%) were treated with 1 or more anti-tumor necrosis factor (TNF) agents. IBD patients with EIM were more likely to be treated with anti-TNF compared to those without (56.4% vs 35.0%, P = 0.003). Response rates to anti-TNF depended on underlying EIM and were best for peripheral arthritis (61.5%) and uveitis (66.7%). In a cohort of pediatric patients with IBD, EIM were frequently encountered. In up to 30%, EIM appeared before IBD diagnosis. Knowledge of these findings may translate into an increased awareness of underlying IBD, thereby decreasing diagnostic delay. Anti-TNF for the treatment of certain EIM is effective, although a substantial proportion of new EIM may present despite ongoing anti-TNF therapy

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Monitoring colonoscopy withdrawal time significantly improves the adenoma detection rate and the performance of endoscopists.

BACKGROUND AND STUDY AIMS The recommended minimum withdrawal time for screening colonoscopy is 6 minutes. Adenoma detection rates (ADRs) increase with longer withdrawal times. We aimed to compare withdrawal times and ADRs of endoscopists unaware of being monitored vs. aware. PATIENTS AND METHODS Seven experienced gastroenterologists prospectively performed 558 screening colonoscopies during a 9-month period in a Swiss University hospital. Colonoscopy withdrawal times were first measured without the gastroenterologists’ knowledge of being monitored (n = 355 colonoscopies) and then with their knowledge (n = 203 colonoscopies). RESULTS The median withdrawal time when gastroenterologists were unaware of being monitored was 4.5 minutes (interquartile range [IQR] 4 – 5.5 minutes) without intervention and 6 minutes (IQR 4 – 9 minutes) with intervention, increasing significantly to 7.3 minutes (IQR 6.5 – 9 minutes) and 8 minutes (IQR 7 – 11 minutes), respectively, when they were aware of being monitored (P < 0.001 both for colonoscopies with and without intervention). The ADR increased from 21.4 % when the gastroenterologists were unaware of being monitored to 36.0 % when they were aware (P < 0.001). In the multivariate regression model, the endoscopists knowing they were being monitored was the strongest factor associated with ADR (odds ratio 4.417; 95 % confidence interval [CI] 2.241 – 8.705; P < 0.001). CONCLUSIONS Colonoscopy withdrawal time in unmonitored gastroenterologists is shorter than recommended and increases with awareness of monitoring. ADR significantly increases when gastroenterologists are aware of being monitored. Implementation of systematic monitoring, and analysis of withdrawal time and ADR for each endoscopist may help to increase the ADR