Randomised controlled trial of mesalazine in IBS.

OBJECTIVE: Low-grade intestinal inflammation plays a role in the pathophysiology of IBS. In this trial, we aimed at evaluating the efficacy and safety of mesalazine in patients with IBS. DESIGN: We conducted a phase 3, multicentre, tertiary setting, randomised, double-blind, placebo-controlled trial in patients with Rome III confirmed IBS. Patients were randomly assigned to either mesalazine, 800 mg, or placebo, three times daily for 12 weeks, and were followed for additional 12 weeks. The primary efficacy endpoint was satisfactory relief of abdominal pain/discomfort for at least half of the weeks of the treatment period. The key secondary endpoint was satisfactory relief of overall IBS symptoms. Supportive analyses were also performed classifying as responders patients with a percentage of affirmative answers of at least 75% or >75% of time. RESULTS: A total of 185 patients with IBS were enrolled from 21 centres. For the primary endpoint, the responder patients were 68.6% in the mesalazine group versus 67.4% in the placebo group (p=0.870; 95% CI -12.8 to 15.1). In explorative analyses, with the 75% rule or >75% rule, the percentage of responders was greater in the mesalazine group with a difference over placebo of 11.6% (p=0.115; 95% CI -2.7% to 26.0%) and 5.9% (p=0.404; 95% CI -7.8% to 19.4%), respectively, although these differences were not significant. For the key secondary endpoint, overall symptoms improved in the mesalazine group and reached a significant difference of 15.1% versus placebo (p=0.032; 95% CI 1.5% to 28.7%) with the >75% rule. CONCLUSIONS: Mesalazine treatment was not superior than placebo on the study primary endpoint. However, a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy. TRIAL REGISTRATION NUMBER: ClincialTrials.gov number, NCT00626288.

Leaky gut, microbiota, and cancer: an incoming hypothesis.

Multigenic disease development is dependent on both missing and overactivated pathways, just as the homeostasis of our body systems is the product of many complex, redundant mechanisms. The goal of finding a common factor in the disease pathogenesis is difficult, as genetic and pathophysiological data are still incomplete, and the individual variability is enormous. Nevertheless, the examination of the role of human microbiota in illnesses using animal models of human diseases reared in defined (gnotobiotic) conditions could allow insight into the unusual complexity of the mechanisms involved in the initiation and maintenance of chronic diseases, including cancer. Although the most important findings in this fascinating field are still to come, a hypothesis, which is more than speculative, can be made, as it is clear that our bacterial companions affect our fates more than previously assumed.

Prediction of oesophageal varices in hepatic cirrhosis by simple serum non-invasive markers: Results of a multicenter, large-scale study.

BACKGROUND & AIMS: Preliminary data suggest that non-invasive methods could be useful to assess presence of oesophageal varices (OV) in cirrhotic patients. We aimed to further investigate simple serum non-invasive markers for diagnosing and grading OV. METHODS: A retrospective set of 510 cirrhotics and a prospective set of 110 cirrhotics were enrolled consecutively in five centers. Platelets, AST-to-ALT ratio, AST-to-platelet-ratio index, Forns' index, Lok index, Fib-4, and Fibroindex were measured within 2 months from upper endoscopy, taken as a gold standard. Performance was expressed as sensitivity, specificity, positive, and negative predictive values (PPV, NPV), accuracy, and area under the curve (AUC). RESULTS: A combination of Lok index (cutoff=1.5) and Forns' index (cutoff=8.8) had 0.80 AUC (0.76-0.84, 95% CI), and high NPV (>90%) to exclude clinically relevant OV, defined as large OV or small OV with red signs or in Child-Pugh C cirrhosis. By applying this combination, upper endoscopy would have been avoided in 1/3 of our cirrhotics. Large OV could be excluded with 96% NPV by Lok index (cutoff=1.5). A combination of Lok index (cutoff=0.9) and Forns' index (cutoff=8.5) predicted presence of any grade OV with good performance: 0.82 AUC (0.76-0.88, 95% CI), 88% PPV. CONCLUSIONS: Serum non-invasive markers may be useful as a first line tool to identify cirrhotic patients in which the risk of clinically relevant OV is trivial, and to reduce the number of upper endoscopies. However, we are still far from the possibility of replacing upper endoscopy by simple serum non-invasive markers in the vast majority of patients.

Probiotics in the treatment of irritable bowel syndrome.

Irritable Bowel Syndrome (IBS) may be diagnosed on the presence of symptoms, according to Rome II criteria, [corrected] and some studies have shown that abnormal colonic fermentation may be an important factor in the development of symptoms in some patients with IBS. Since the fermentation [corrected] of substrates by the intestinal flora may play a key role in the use of probiotics in the treatment of IBS, seventy [corrected] patients (31 [corrected] males, 39 [corrected] females), mean age 40 years (range = 26-64 years) with IBS, according to Rome II criteria, were enrolled into the study after informed consensus. Patients were randomly assigned to receive for 4 weeks [corrected] either the active preparation containing Lactobacillus plantarum LP 01 [corrected] and Bifidobacterium breve BR 03 [corrected] or Lactobacillus plantarum LP 01 and Lactobacillus acidophilus LA 02, all strains at concentrations of 5 x 10(9) CFU/g) [corrected] or placebo powder containing starch identical to the study product [corrected] To evaluate treatment efficacy two different scores were considered [corrected] Pain score in different abdominal locations after treatment decreased in probiotics groups A and B 42% and 49% versus 25% [corrected] (P < 0.05) in [corrected] placebo group after 14 days and 45% and 49% versus 29.5% [corrected] (P < 0.001) after 28 days. The severity score of characteristic IBD symptoms significantly decreased in probiotic groups A and B [corrected] versus placebo group after 14 days, 49.3% and 55.6% [corrected] versus 8% [corrected] (P < 0.001), and these data were confirmed after 28 days (56% and 55.6% versus 14.4% [corrected] P < 0.001). In conclusion, short-term therapy with Lactobacillus plantarum LP 01 and Bifidobacterium breve BR 03 or Lactobacillus plantarum LP 01 and Lactobacillus acidophilus LA 02 [corrected] may be considered a promising approach for IBS therapy [corrected]