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.

Background: Biologic disease-modifying drugs have revolutionised the treatment of a number of chronic inflammatory diseases (CID). However, up to 60% of the patients do not have a sufficient response to treatment and there is a need for optimization of treatment strategies.Objective: To investigate if the treatment outcome of biological therapy is associated with the habitual dietary intake of fibre and red/processed meat in patients with a CID.Methods: In this multicentre prospective cohort study, we consecutively enrolled 233 adult patients with a diagnosis of Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis (RA), Axial Spondyloarthritis, Psoriatic Arthritis and Psoriasis, for whom biologic therapy was planned, over a 3 year period. Patients with completed baseline food frequency questionnaires were stratified into a high fibre/low red and processed meat exposed group (HFLM) and an unexposed group (low fibre/high red and processed meat intake = LFHM). The primary outcome was the proportion of patients with a clinical response to biologic therapy after 14–16 weeks of treatment.Results: Of the 193 patients included in our primary analysis, 114 (59%) had a clinical response to biologic therapy. In the HFLM group (N = 64), 41 (64%) patients responded to treatment compared to 73 (56%) in the LFHM group (N = 129), but the difference was not statistically significant (OR: 1.48, 0.72–3.05). For RA patients however, HFLM diet was associated with a more likely clinical response (82% vs. 35%; OR: 9.84, 1.35–71.56).Conclusion: Habitual HFLM intake did not affect the clinical response to biological treatment across CIDs. HFLM diet in RA patients might be associated with better odds for responding to biological treatment, but this would need confirmation in a randomised trial.Trial registration: (clinicaltrials.gov), identifier [NCT03173144].

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.

Background: Currently, there are no reliable biomarkers for predicting treatment response in chronic inflammatory diseases (CIDs). Objective: To determine whether serum microfibrillar-associated protein 4 (MFAP4) levels can predict the treatment response to biological therapy in patients with CIDs. Methods: The BELIEVE study was originally designed as a prospective, multi-center cohort study of 233 patients with either rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, Crohn’s disease, or ulcerative colitis, initiating treatment with a biologic agent (or switching to another). Clinical assessment and blood sample collection were performed at baseline and 14–16 weeks after treatment initiation. The primary analyses included participants with available blood samples at baseline; missing data were handled as non-responders. The patients were stratified into the upper tertile of serum MFAP4 (High MFAP4) versus a combined category of middle and lower tertiles (Other MFAP4). The primary outcome was the proportion of patients with clinical response to biologic therapy after 14–16 weeks. Results: 211 patients were included in the primary analysis population. The mean age was 43.7 (SD: 14.8) years, and 120 (59%) were female. Positive treatment response was observed in 41 (59%) and 69 (49%) for High MFAP4 and Other MFAP4, respectively. When adjusting for pre-specified variables (CID, age, sex, smoking status, and BMI), the adjusted OR was 2.28 (95% CI: 1.07 to 4.85) for a positive treatment outcome in the High MFAP4 group. Conclusion: A high MFAP4 status before initiating biological treatment is associated with a positive clinical response, when adjusting for confounding factors.

The objective of this meta‐epidemiological study was to explore the impact of attrition rates on treatment effect estimates in randomised trials of chronic inflammatory diseases (CID) treated with biological and targeted synthetic disease‐modifying drugs. We sampled trials from Cochrane reviews. Attrition rates and primary endpoint results were retrieved from trial publications; Odds ratios (ORs) were calculated from the odds of withdrawing in the experimental intervention compared to the control comparison groups (i.e., differential attrition), as well as the odds of achieving a clinical response (i.e., the trial outcome). Trials were combined using random effects restricted maximum likelihood meta‐regression models and associations between estimates of treatment effects and attrition rates were analysed. From 37 meta‐analyses, 179 trials were included, and 163 were analysed (301 randomised comparisons; n = 62,220 patients). Overall, the odds of withdrawal were lower in the experimental compared to control groups (random effects summary OR = 0.45, 95% CI, 0.41–0.50). The corresponding overall treatment effects were large (random effects summary OR = 4.43, 95% CI 3.92–4.99) with considerable heterogeneity across interventions and clinical specialties (I² = 85.7%). The ORs estimating treatment effect showed larger treatment benefits when the differential attrition was more prominent with more attrition in the control group (OR = 0.73, 95% CI 0.55–0.96). Higher attrition rates from the control arm are associated with larger estimated benefits of treatments with biological or targeted synthetic disease‐modifying drugs in CID trials; differential attrition may affect estimates of treatment benefit in randomised trials.

Background. Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a complex inflammatory condition affecting the intestinal tract. Currently, immune-modulating treatments are inadequate for 30–50% of patients and often cause significant side effects, highlighting the urgent need for a personalized medicine approach. Real-world data and archived gut biological material from clinical repositories could be a resource for identifying new drug candidates and biomarkers. This study assesses the extent of stored formalin-fixed, paraffin-embedded (FFPE) gut biopsies from patients with IBD that could be leveraged for research efforts. Methods. Data from the Danish National Patient Register and the Danish Pathology Register were used to construct a cohort of patients diagnosed with IBD between 1 January 2005, and 30 June 2013, and followed for five years. Results. Among 14,512 IBD patients, 13,936 (96%) had at least one biopsy visit within five years after their initial diagnosis (CD 94%, UC 97%), and 13,598 (94%) had their first biopsy visit as part of the diagnostic process. Biopsies were taken from the colon (82%) or multiple locations (46%). Patients with severe disease had more biopsy visits than those with non-severe disease (IBD 3.3 vs. 2.0 visits, CD 2.9 vs. 1.9 visits, UC 3.6 vs. 2.0 visits). Conclusions. Thus, the vast majority of patients with IBD have biopsies taken. These findings demonstrate the feasibility and applicability of combining real-world data and archived gut biopsies for research, highlighting it as a valuable but underutilized resource for identifying new drug candidates and biomarkers, with huge potential for enhancing personalized medicine within IBD for the benefit of patients and society.