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Background SPD476 (MMX™ mesalazine), is a novel, once daily, high-strength mesalazine formulation (1.2 g/tablet) that utilizes Multi Matrix System™ (MMX) technology to delay and extend delivery of the active drug throughout the colon. Aim To assess the safety and efficacy of MMX mesalazine in patients with mild-to-moderately active ulcerative colitis, in a pilot, phase II, randomized, multicentre, double-blind, parallel-group, dose-ranging study (SPD476-202). Methods Thirty-eight patients with mild-to-moderately active ulcerative colitis were randomized to MMX mesalazine 1.2, 2.4 or 4.8 g/day given once daily for 8 weeks. Remission ulcerative colitis-disease activity index (UC-DAI) ≤1, a score of 0 for rectal bleeding and stool frequency, and ≥1-point reduction in sigmoidoscopy score from baseline was the primary end point. Results Week 8 remission rates were 0%, 31% and 18% of patients receiving MMX mesalazine 1.2, 2.4 and 4.8 g/day respectively. No statistically significant difference in remission was observed between treatment groups. MMX mesalazine 2.4 and 4.8 g/day groups demonstrated greater improvement in overall UC-DAI and component scores from baseline, compared with the 1.2 g/day group. Conclusion MMX mesalazine given as 2.4 or 4.8 g/day once daily is well tolerated and effective for the treatment of mild-to-moderately active ulcerative colitis. [ABSTRACT FROM AUTHOR]

One of the major advances in the understanding of inflammatory bowel disease has been the observation that mice with immunoregulatory defects, such as interleukin-2 knockout (IL-2 -/-) mice, develop spontaneous gut inflammation. Here we have characterized the immune response in the ileum, caecum and colon of these mice before and after the onset of colitis by examining the cellular infiltrate, the cytokines produced by these cells and the mucosal vascular addressin MAdCAM-1. IL-2 -/- mice developed colitis after 35 days of age and before this the mice were apparently healthy. IL-2 -/- mice aged over 35 days with colitis had large numbers of CD4+, CD8+, αβ T-cell receptor (TCR)+ and γδ TCR+ T-cells, macrophages, dendritic cells and MAdCAM-1+ endothelial cells in the caecum and colon. This was associated with an increase in the number of interferon-γ (IFN-γ), IL-1 and tumour necrosis factor-α (TNF-α) transcripts and a decrease in IL-4 and IL-10 transcripts. Treatment of IL-2 -/- mice with cyclosporin A significantly delayed mortality. Interestingly, IL-2 -/- mice under 35 days, although healthy, did show some subtle immunological signs of preclinical disease. There was a significant increase in the number of macrophages and dendritic cells in the colonic lamina propria and increased mRNA for IL-1 and TNF-α. There were also increased numbers of MAdCAM-1+ endothelial cells, but IFN-γ transcripts were not elevated. These results suggest that T-cell-mediated colitis in IL-2 -/- mice may be secondary to an initial non-specific inflammation. [ABSTRACT FROM AUTHOR]

Objective: The hemodynamic effect and early and late survival impact of prosthesis-patient mismatch (PPM) after mitral valve replacement remains insufficiently explored., Methods: Pubmed, Embase, Web of Science, and Cochrane Library databases were searched for English language original publications. The search yielded 791 potentially relevant studies. The final review and analysis included 19 studies compromising 11,675 patients., Results: Prosthetic effective orifice area was calculated with the continuity equation method in 7 (37%), pressure half-time method in 2 (10%), and partially or fully obtained from referenced values in 10 (53%) studies. Risk factors for PPM included gender (male), diabetes mellitus, chronic renal disease, and the use of bioprostheses. When pooling unadjusted data, PPM was associated with higher perioperative (odds ratio [OR]: 1.66; 95% confidence interval [CI]: 1.32-2.10; p < .001) and late mortality (hazard ratio [HR]: 1.46; 95% CI: 1.21-1.77; p < .001). Moreover, PPM was associated with higher late mortality when Cox proportional-hazards regression (HR: 1.97; 95% CI: 1.57-2.47; p < .001) and propensity score (HR: 1.99; 95% CI: 1.34-2.95; p < .001) adjusted data were pooled. Contrarily, moderate (HR: 1.01; 95% CI: 0.84-1.22; p = .88) or severe (HR: 1.19; 95% CI: 0.89-1.58; p = .24) PPM were not related to higher late mortality when adjusted data were pooled individually. PPM was associated with higher systolic pulmonary pressures (mean difference: 7.88 mmHg; 95% CI: 4.72-11.05; p < .001) and less pulmonary hypertension regression (OR: 5.78; 95% CI: 3.33-10.05; p < .001) late after surgery., Conclusions: Mitral valve PPM is associated with higher postoperative pulmonary artery pressure and might impair perioperative and overall survival. The relation should be further assessed in properly designed studies., (© 2020 The Authors. Journal of Cardiac Surgery published by Wiley Periodicals LLC.)

This study assessed the effect of treating nicotine dependence in smokers undergoing inpatient treatment for other addictions. It was a prospective, nonrandomized, controlled trial with a 1-year outcome. The subjects were smoking patients (50 controls, 51 in intervention group) in an inpatient addictions treatment unit in a medical center. The enrollment of subjects was sequential: controls were enrolled first; after a 6-week washout period, intervention subjects were enrolled. Controls received usual care, and the intervention group received nicotine dependence treatment consisting of a consultation, 10 intervention sessions, and a structured relapse prevention program. Smoking cessation rate and abstinence from alcohol or other drug use were the main outcome measures. The confirmed smoking cessation rate at 1 year was 11.8% in the intervention group and 0.0% in the control group (p = 0.027). Nicotine dependence intervention did not seen to interfere with abstinence from alcohol or other drugs (1-year relapse rate was 31.4% in the intervention group and 34.0% in controls). In this study, nicotine dependence treatment provided as part of addictive disorders treatment enhanced smoking cessation and did not have a substantial adverse effect on abstinence from the nonnicotine drug of dependence.