Faecal microbiota signatures of IBD and their relation to diagnosis, disease phenotype, inflammation, treatment escalation and anti-TNF response in a European Multicentre Study (IBD-Character).

METHOD: We examined faecal samples, using the GA-map™ Dysbiosis Test, to associate gut microbiota composition with Crohn's disease (CD) and ulcerative colitis (UC) and to identify markers for future biomarker identification. We conducted a prospective case-control study (EU-ref. no. 305676) in an inception cohort of 324 individuals (64 CD, 84 UC, 116 symptomatic non-IBD controls and 44 healthy controls) across five European centres and examined 54 predetermined bacterial markers. We categorized patients according to the Montreal Classification and calculated the dysbiosis index (DI). Non-parametric tests were used to compare groups and the Bonferroni correction to adjust for multiple comparisons. RESULTS: The fluorescent signals (FSSs) for Firmicutes and Eubacterium hallii were lower in inflammatory bowel disease (IBD) vs. symptomatic controls (p<.05). FSS for Firmicutes, Lachnospiraceae, Eubacterium hallii and Ruminococcus albus/bromii were lower, whereas the signal for Bacteroides Fragilis was higher in UC vs. symptomatic controls (p<.05). FSS was higher for Bifidobacterium spp., Eubacterium hallii, Actinobacteria and Firmicutes among patients with ulcerative proctitis, compared to extensive colitis (p<.05). In CD, we observed no association with disease location. The DI correlated with faecal-calprotectin in both CD and in UC (p<.001). In terms of treatment escalation and anti-TNF response, differences were observed for some bacterial markers, but none of these associations were statistically significant. CONCLUSION: Our data reveal that the GA-map™ Dysbiosis Test holds the potential to characterize the faecal microbiota composition and to assess the degree of dysbiosis in new-onset IBD. On the other hand, our results cannot demonstrate any proven diagnostic or predictive value of this method to support clinical decision making.

Intraoperative force-setting did not improve the mechanical properties of an augmented bone-tendon-bone anterior cruciate ligament graft in a goat model.

It has been hypothesized that load affects the mechanical properties of an anterior cruciate ligament graft while it remodels. The goal of this study was to use an existing goat model to evaluate the effect of intraoperative set force on the postoperative mechanical properties of an autograft that had been augmented with a synthetic segment. The following questions were addressed. Do augmented autografts set with a high force intraoperatively have improved structural and material graft properties and lower anterior-posterior knee laxity at 3 months after surgery, compared with autografts set with a low intraoperative force? How do the structural and material properties of these implanted autografts compare with the mechanical properties of an intact anterior cruciate ligament or an unimplanted control autograft? The anterior cruciate ligament was reconstructed in seven goats with use of a composite graft consisting of a bone-patellar tendon-bone autograft and a synthetic augmentation device. A force-setting technique was used intraoperatively to establish the load-sharing between the autograft and augmentation segments such that the autograft carried either a high (16.5 N in four animals) or low (1.5 N in three animals) level of force, while the total force in the composite graft remained constant. Tensile testing was performed at 3 months after surgery to determine the material and structural properties of the autograft, the intact anterior cruciate ligament from the normal contralateral knee, and a control bone-patellar tendon-bone graft of similar size that was harvested from the contralateral knee at the time of necropsy and had never been implanted in the joint. The structural and material properties of the autografts initially set to high or low loads at surgery were not significantly different after 3 months of implantation. The strength and stiffness of the implanted tendons were an average of 24 and 20% of the strength and stiffness of the normal anterior cruciate ligament and 31 and 62% of the control tendons, respectively. Intraoperative set force in an augmented anterior cruciate ligament graft at the levels chosen in this study did not significantly affect weakening of the autograft at 3 months.

Description and application of instrumented staples for measuring in vivo bone strain.

In vivo bone strain measurements using strain gages cemented to bony surfaces with cyanoacrylate polymers are limited in duration due to debonding of the gages from bone. As an alternative to the bone bonded strain gages, a technique was developed in which strain gages were first bonded to miniature staples and then the staples embedded into bone. The instrumented staples may be calibrated so that staple strain is directly proportional to bone strain. The method was first validated by comparing the staple output with cemented surface strain gages. Comparison of instrumented staples to cemented strain gages revealed only a 3% deviation from linearity during longitudinal bending; the staples were insensitive to transverse loading. The instrumented staples were then applied to the in vitro canine lumbar spine to determine L2-3 facet loads. Load testing, repeatibility of facet calibration, and validity testing of the in vitro instrumented staples were found to be comparable to that of the previous cemented strain gage techniques. In vivo facet joint application of the instrumented staples for periods of greater than 5 weeks gave load measurements comparable to our previous short-term in vivo studies obtained with cemented strain gages. The advantages of the instrumented staples are a more secure bonding to the bone, and less traumatic surgery for fixation.