Effects of smoking on clinical treatment outcomes amongst patients with chronic inflammatory diseases initiating biologics: secondary analyses of the prospective BELIEVE cohort study.

The prevalence and disease burden of chronic inflammatory diseases (CIDs) are predicted to rise. Patients are commonly treated with biological agents, but the individual treatment responses vary, warranting further research into optimizing treatment strategies. This study aimed to compare the clinical treatment responses in patients with CIDs initiating biologic therapy based on smoking status, a notorious risk factor in CIDs. In this multicentre cohort study including 233 patients with a diagnosis of Crohn's disease, ulcerative colitis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis or psoriasis initiating biologic therapy, we compared treatment response rates after 14 to 16 weeks and secondary outcomes between smokers and non-smokers. We evaluated the contrast between groups using logistic regression models: (i) a "crude" model, only adjusted for the CID type, and (ii) an adjusted model (including sex and age). Among the 205 patients eligible for this study, 53 (26%) were smokers. The treatment response rate among smokers (n = 23 [43%]) was lower compared to the non-smoking CID population (n = 92 [61%]), corresponding to a "crude" OR of 0.51 (95% CI: [0.26;1.01]) while adjusting for sex and age resulted in consistent findings: 0.51 [0.26;1.02]. The contrast was apparently most prominent among the 38 RA patients, with significantly lower treatment response rates for smokers in both the "crude" and adjusted models (adjusted OR 0.13, [0.02;0.81]). Despite a significant risk of residual confounding, patients with CIDs (rheumatoid arthritis in particular) should be informed that smoking probably lowers the odds of responding sufficiently to biological therapy. Registration: Clinical.Trials.gov NCT03173144.

Bovine Milk Oligosaccharides with Sialyllactose Improves Cognition in Preterm Pigs.

Optimal nutrition is important after preterm birth to facilitate normal brain development. Human milk is rich in sialic acid and preterm infants may benefit from supplementing formula with sialyllactose to support neurodevelopment. Using pigs as models, we hypothesized that sialyllactose supplementation improves brain development after preterm birth. Pigs (of either sex) were delivered by cesarean section at 90% gestation and fed a milk diet supplemented with either an oligosaccharide-enriched whey with sialyllactose (n = 20) or lactose (n = 20) for 19 days. Cognitive performance was tested in a spatial T-maze. Brains were collected for ex vivo magnetic resonance imaging (MRI), gene expression, and sialic acid measurements. For reference, term piglets (n = 14) were artificially reared under identical conditions and compared with vaginally born piglets naturally reared by the sow (n = 12). A higher proportion of sialyllactose supplemented preterm pigs reached the T-maze learning criteria relative to control preterm pigs (p < 0.05), and approximated the cognition level of term reference pigs (p < 0.01). Furthermore, supplemented pigs had upregulated genes related to sialic acid metabolism, myelination, and ganglioside biosynthesis in hippocampus. Sialyllactose supplementation did not lead to higher levels of sialic acid in the hippocampus or change MRI endpoints. Contrary, these parameters were strongly influenced by postconceptional age and postnatal rearing conditions. In conclusion, oligosaccharide-enriched whey with sialyllactose improved spatial cognition, with effects on hippocampal genes related to sialic acid metabolism, myelination, and ganglioside biosynthesis in preterm pigs. Dietary sialic acid enrichment may improve brain development in infants.