Impact of the early use of immunomodulators or TNF antagonists on bowel damage and surgery in Crohn's disease.

BACKGROUND The impact of early treatment with immunomodulators (IM) and/or TNF antagonists on bowel damage in Crohn's disease (CD) patients is unknown. AIM To assess whether 'early treatment' with IM and/or TNF antagonists, defined as treatment within a 2-year period from the date of CD diagnosis, was associated with development of lesser number of disease complications when compared to 'late treatment', which was defined as treatment initiation after >2 years from the time of CD diagnosis. METHODS Data from the Swiss IBD Cohort Study were analysed. The following outcomes were assessed using Cox proportional hazard modelling: bowel strictures, perianal fistulas, internal fistulas, intestinal surgery, perianal surgery and any of the aforementioned complications. RESULTS The 'early treatment' group of 292 CD patients was compared to the 'late treatment' group of 248 CD patients. We found that 'early treatment' with IM or TNF antagonists alone was associated with reduced risk of bowel strictures [hazard ratio (HR) 0.496, P = 0.004 for IM; HR 0.276, P = 0.018 for TNF antagonists]. Furthermore, 'early treatment' with IM was associated with reduced risk of undergoing intestinal surgery (HR 0.322, P = 0.005), and perianal surgery (HR 0.361, P = 0.042), as well as developing any complication (HR 0.567, P = 0.006). CONCLUSIONS Treatment with immunomodulators or TNF antagonists within the first 2 years of CD diagnosis was associated with reduced risk of developing bowel strictures, when compared to initiating these drugs >2 years after diagnosis. Furthermore, early immunomodulators treatment was associated with reduced risk of intestinal surgery, perianal surgery and any complication.

Revision of the early-middle Pleistocene calcareous nannofossil biochronology

The extant nannofossil biostratigraphic and biochronologic framework for the early-middle Pleistocene time interval has been tested through the micropaleontological analysis of globally distributed high-quality low- to mid-latitude deep-sea successions. The quantitative temporal distribution patterns of relative abundances of selected taxa were reconstructed in critical intervals, and the following biohorizons were defined: first occurrence of medium-sized Gephyrocapsa spp. (bmG); last occurrence of Calcidiscus macintyrei (tCm); first occurrence of large Gephyrocapsa spp. (blG); last occurrence of large Gephyrocapsa spp. (tlG); first occurrence of Reticulofenestra asanoi (bRa); re-entrance of medium-sized Gephyrocapsa spp. (reemG) and last occurrence of Reticulofenestra asanoi (tRa). The detailed patterns of abundance change at these biohorizons were used to generate a detailed biostratigraphy, and the biostratigraphic data were transformed into a precise biochronology by means of correlation to isotope stratigraphies and astronomical timescales. The degree of isochrony or diachrony of the biohorizons was evaluated. Biohorizons tlG and tRa are isochronous occurring close to marine isotope stages (MIS)55 and MIS 22, respectively, and bmG and blG are slightly diachronous on the order of 30-40 kyr, whereas biohorizons tCm, reemG and bRa are confirmed as diachronous on the order of 100, 80 and 60 kyr, respectively. Some of the events are clearly controlled by environmental conditions, e.g. the last occurrence of R. asanoi, related to significant environmental changes associated with the first large-amplitude glaciation of the late Quaternary, MIS 22.