Gaston Bachelard and Contemporary Philosophy

This special issue aims to redress the balance and to open up Gaston Bachelard's work beyond a small in-crowd of experts and aficionado’s in France. It aims to stimulate the discovery of new and understudied aspects of Bachelard’s work, including aspects of the intellectual milieu he was working in. Fortunately, for this purpose we were able to rely both on renowned Bachelard specialists, such as Hans-Jörg Rheinberg-er, Cristina Chimisso and Dominique Lecourt, as well as on a number of younger scholars who are discovering their work in a different intellectual context. At the same time we also want to reassess the value of this oeuvre, which also entails examining the reasons and causes of the relative neglect of Bachelard’s work in recent times. Has it exhausted its possibilities? Does it have intrinsic limitations that have contributed to the eclipse, as some influential, mainly French, philoso-phers have more or less explicitly suggested

Vaccination and infection prevention in inflammatory bowel disease

The current medical therapy used in Crohn’s disease and ulcerative colitis comprises drugs that interfere with immune response and therefore caution is needed for infectious side effects, and where possible, strategies to prevent their occurrence should be undertaken. Last year, international consensus guidelines on this topic were published by the European Crohn’s and Colitis Organisation

Dysbiosis of the faecal microbiota in patients with Crohn's disease and their unaffected relatives

Background and aims A general dysbiosis of the intestinal microbiota has been established in patients with Crohn's disease (CD), but a systematic characterisation of this dysbiosis is lacking. Therefore the composition of the predominant faecal microbiota of patients with CD was studied in comparison with the predominant composition in unaffected controls. Whether dysbiosis is present in relatives of patients CD was also examined. Methods Focusing on families with at least three members affected with CD, faecal samples of 68 patients with CD, 84 of their unaffected relatives and 55 matched controls were subjected to community fingerprinting of the predominant microbiota using denaturing gradient gel electrophoresis (DGGE). To analyse the DGGE profiles, BioNumerics software and non-parametric statistical analyses (SPSS V. 17.0) were used. Observed differences in the predominant microbiota were subsequently confirmed and quantified with real-time PCR. Results Five bacterial species characterised dysbiosis in CD, namely a decrease in Dialister invisus (p = 0.04), an uncharacterised species of Clostridium cluster XIVa (p = 0.03), Faecalibacterium prausnitzii (p<1.3x10(-5)) and Bifidobacterium adolescentis (p = 5.4x10(-6)), and an increase in Ruminococcus gnavus (p = 2.1x10(-7)). Unaffected relatives of patients with CD had less Collinsella aerofaciens (p = 0.004) and a member of the Escherichia coli-Shigella group (p = 0.01) and more Ruminococcus torques (p = 0.02) in their predominant microbiota as compared with healthy subjects. Conclusion Unaffected relatives of patients with CD have a different composition of their microbiota compared with healthy controls. This dysbiosis is not characterised by lack of butyrate producing-bacteria as observed in CD but suggests a role for microorganisms with mucin degradation capacity

A Pooled Analysis of Infections, Malignancy, and Mortality in Infliximab- and Immunomodulator-Treated Adult Patients With Inflammatory Bowel Disease

The objective of this study was to analyze the safety of long-term infliximab treatment, with/without concomitant immunomodulators, across Crohn's disease (CD) and ulcerative colitis (UC) clinical trials.status: publishe

A randomised phase I study of etrolizumab (rhuMAb β7) in moderate to severe ulcerative colitis.

ObjectiveEtrolizumab (rhuMAb β7, anti-β7, PRO145223) is a humanised monoclonal antibody targeting the β7 subunit of the heterodimeric integrins α4β7 and αEβ7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC.DesignIn the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD).ResultsIn the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of β7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively.ConclusionEtrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted

Molecular Reclassification of Crohn's Disease by Cluster Analysis of Genetic Variants

Background Crohn's Disease (CD) has a heterogeneous presentation, and is typically classified according to extent and location of disease. The genetic susceptibility to CD is well known and genome-wide association scans (GWAS) and meta-analysis thereof have identified over 30 susceptibility loci. Except for the association between ileal CD and NOD2 mutations, efforts in trying to link CD genetics to clinical subphenotypes have not been very successful. We hypothesized that the large number of confirmed genetic variants enables (better) classification of CD patients. Methodology/Principal Findings To look for genetic-based subgroups, genotyping results of 46 SNPs identified from CD GWAS were analyzed by Latent Class Analysis (LCA) in CD patients and in healthy controls. Six genetic-based subgroups were identified in CD patients, which were significantly different from the five subgroups found in healthy controls. The identified CD-specific clusters are therefore likely to contribute to disease behavior. We then looked at whether we could relate the genetic-based subgroups to the currently used clinical parameters. Although modest differences in prevalence of disease location and behavior could be observed among the CD clusters, Random Forest analysis showed that patients could not be allocated to one of the 6 genetic-based subgroups based on the typically used clinical parameters alone. This points to a poor relationship between the genetic-based subgroups and the used clinical subphenotypes. Conclusions/Significance This approach serves as a first step to reclassify Crohn's disease. The used technique can be applied to other common complex diseases as well, and will help to complete patient characterization, in order to evolve towards personalized medicine. </sec