Background and aims: Experimental studies have shown that luminal bacteria may be involved in Crohn's disease. Probiotics are a possible alternative to antibiotics. The aim of this randomised placebo ...controlled study was to determine if Lactobacillus GG, given by mouth for one year, could prevent Crohn's recurrent lesions after surgery or to reduce their severity. Methods: Patients operated on for Crohn's disease in whom all of the diseased gut had been removed were randomly allocated to receive 12 billion colony forming units of Lactobacillus or identical placebo for one year. Ileocolonoscopy was performed at the end of the trial or at the onset of symptoms. Endoscopic recurrence was defined as grade 2 or higher of Rutgeerts scoring system. Results: Eight of 45 patients were excluded from the trial (three for non-compliance and five for protocol violations). Clinical recurrence was ascertained in three (16.6%) patients who received Lactobacillus and in two (10.5%) who received placebo. Nine of 15 patients in clinical remission on Lactobacillus (60%) had endoscopic recurrence compared with six of 17 (35.3%) on placebo (p=0.297). There were no significant differences in the severity of the lesions between the two groups. Conclusions:Lactobacillus GG seems neither to prevent endoscopic recurrence at one year nor reduce the severity of recurrent lesions.
Summary
Background Clinicians often employ antibiotics in Crohn's disease. Rifaximin is active against bacteria frequently found in the intestinal mucosa of Crohn's disease patients.
Aim To ...evaluate the difference in efficacy between once and twice/daily oral administration of rifaximin and placebo in the treatment of active Crohn's disease.
Methods We enrolled 83 patients with mild‐to‐moderate Crohn's disease and randomized to three treatments for 12 weeks: Group A (rifaximin 800 mg o.d. + placebo), Group B (rifaximin 800 mg b.d.) and Group C (placebo b.d.).
Results Clinical remission was achieved by 52% of Group B, 32% (A) and 33% (C). Clinical response was seen in 67% (B), 48% (A) and 41% (C), without reaching a statistically significant difference. Treatment failures were: 4% (B), 12% (A) and 33% (C), (P = 0.010). Remission and response rates of rifaximin 800 mg b.d. were significantly higher than those of placebo and rifaximin 800 mg o.d. in patients with elevated C reactive protein values (P < 0.05).
Conclusions Rifaximin 800 mg b.d. was superior to placebo in inducing clinical remission of active Crohn's disease. Although this difference was not statistically significant, the number of the failures in the placebo group was significantly higher than those who received rifaximin 800 mg b.d.
Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 ...signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7.
In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28.
The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P<0.001). There was no significant difference in the percentage of participants reaching clinical remission between the 10-mg group (12%) and the placebo group. The rate of clinical response was significantly greater among patients receiving 10 mg (37%), 40 mg (58%), or 160 mg (72%) of mongersen than among those receiving placebo (17%) (P=0.04, P<0.001, and P<0.001, respectively). Most adverse events were related to complications and symptoms of Crohn's disease.
We found that study participants with Crohn's disease who received mongersen had significantly higher rates of remission and clinical response than those who received placebo. (Funded by Giuliani; EudraCT number, 2011-002640-27.).
We sought to determine whether psychosocial factors influence the course of ulcerative colitis, hypothesizing that high perceived stress among patients with inactive disease will increase the risk of ...subsequent exacerbation.
Sixty-two patients with known ulcerative colitis were enrolled into a prospective cohort study while in clinical remission. Their perceived stress, depressive symptoms, and stressful life events were followed, along with potential confounders, for up to 45 months; exacerbation status was monitored for up to 68 months.
The 27 patients who experienced an exacerbation were compared with those who remained in remission. Having a score in the upper tertile on the long-term (past 2 yr) baseline Perceived Stress Questionnaire significantly increased the actuarial risk of exacerbation (hazards ratio = 2.8, 95% confidence interval 1.1-7.2). At any given study visit, high long-term stress tripled the risk of exacerbation during the next 8 months (risk for the three tertiles, 8.3%, 16.7%, and 26.2%, p = 0.02). Shorter sleep time, briefer remission, histological activity, and use of nonsteroidal antiinflammatory drugs, antibiotics, or oral contraceptives also increased the medium- and/or long-term risk of exacerbation, but adjustment for these variables did not eliminate the associations with stress. Exacerbation was not associated with stressful life events, depressive symptoms, short-term (past month) perceived stress, smoking, disease extent or duration, or severity of recent course.
Short-term stress does not trigger exacerbation in ulcerative colitis, but long-term perceived stress increases the risk of exacerbation over a period of months to years.
A 30-question Perceived Stress Questionnaire (PSQ) was validated, in Italian and English, among 230 subjects. Test-retest reliability was 0.82 for the General (past year or two) PSQ, while monthly ...Recent (past month) PSQs varied by a mean factor of 1.9 over 6 months; coefficient alpha > 0.9. General and/or Recent PSQ scores were associated with trait anxiety (r = 0.75), Cohen's Perceived Stress Scale (r = 0.73), depression (r = 0.56), self-rated stress (r = 0.56), and stressful life events (p < 0.05). The General PSQ was higher in in-patients than in out-patients (p < 0.05); both forms were correlated with a somatic complaints scale in a non-patient population (r > 0.5), and were higher, among 27 asymptomatic ulcerative colitis patients, in the seven who had rectal inflammation than in those with normal proctoscopy (p = 0.03). Factor analysis yielded seven factors, of which those reflecting interpersonal conflict and tension were significantly associated with health outcomes. The Perceived Stress Questionnaire may be a valuable addition to the armamentarium of psychosomatic researchers.
Insulin resistance (IR) reduces response to pegylated‐interferon (PEG‐IFN)/ribavirin in chronic hepatitis C (CHC), but the mechanisms are still undefined. We examined the relationship between ...baseline insulin levels, the main component affecting homeostasis model of assessment – insulin resistance (HOMA‐IR) for assessment of IR in non‐diabetic patients, and the ‘acute’ virological response to PEG‐IFN measured 24 h after the first injection and taken as correlate of intracellular interferon signalling. In 62 patients treated with PEG‐IFN/Ribavirin, serum insulin and HOMA‐IR were assessed at baseline, while hepatitis C virus (HCV)‐RNA was measured at baseline and 24 h, 1, 2, 4 and 12 weeks after treatment initiation. Sustained virological response was examined 24 weeks after therapy discontinuation. Mean baseline insulin was 11.52 ± 8.51 U/L and mean HOMA‐IR was 2.65 ± 2.01 both being significantly higher with advanced liver fibrosis. Hepatitis C virus‐RNA decay observed 24 h after the first injection of PEG‐IFN was significantly lower (0.7 ± 0.8 log) in patients with HOMA ≥3 compared with those with HOMA <3 (1.7 ± 0.8, P = 0.001). A highly significant (r = −0.42) inverse correlation was observed between baseline insulin levels and the 24‐h HCV‐RNA decay. The difference in early viral kinetics between patients with HOMA ≥3 or <3 resulted in a significant difference in the percentage of patients achieving rapid (week 4) and sustained virological response. Multivariate analysis, inclusive of patient age, HCV genotype and fibrosis stage, identified baseline insulin levels as the main independent variable affecting the 24‐h response to PEG‐IFN. Hyperinsulinaemia reduces the cellular response to Pegylated‐interferon in CHC with IR. Strategies to reduce insulin levels before initiation of treatment should be pursued to improve efficacy of anti‐viral treatment.
Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with a 6% to 74% prevalence and a negative impact on patient survival and quality of life, although the ...prevalence is apparently declining due to improved disease treatment. We aimed to investigate the prevalence, pathogenesis, and clinical correlates of anemia in Italian patients with IBD.
A multicenter, prospective, observational study, involving 28 Italian gastroenterology centers, was conducted to investigate the epidemiology and consequences of IBD-associated anemia. Clinical and laboratory data of anemic patients were obtained at study enrolment.
Anemia was diagnosed in 737 of 5416 adult IBD outpatients (prevalence 13.6%); females were more commonly affected than males (odds ratio, 1.5; 95% confidence interval CI, 1.2-1.7) and had more severe anemia. In the majority of cases, anemia was due to iron deficiency (62.5% of cases; 95% CI, 58.3%-66.6%), either isolated or in association with inflammation and/or vitamin deficiencies; anemia of inflammation accounted for only 8.3% of cases. More severe anemia was associated with increasing fatigue and worse quality of life. Only 68.9% of anemic patients with iron deficiency (95% CI, 63.4%-73.8%) and 34.6% of those with vitamin deficiencies (95% CI, 26.2%-44.2%) were properly treated with supplementation therapy.
In Italy, the prevalence of IBD-associated anemia is lower than previously reported. Anemia of IBD is most commonly due to iron deficiency and contributes to fatigue and poor quality of life, but remains untreated in a large proportion of patients with iron and/or vitamin deficiencies. This study is registered at clinicaltrials.gov as NCT02872376.
Bacteria in the gut lumen may play a role in the etiology and/or the symptoms of Crohn's disease (CD). Although various antibacterial drugs have been employed in clinical practice, few controlled ...trials have been conducted, and those had conflicting results. The aim of this study was to investigate the efficacy and the safety of a combination of metronidazole and ciprofloxacin, compared with methylprednisolone, in treating 41 consecutive patients with active CD.
Eligible patients, 13 men and 28 women, mean age 38 yr, were randomly allocated to receive, for 12 wk, ciprofloxacin 500 mg twice daily plus metronidazole 250 mg four times daily or methylprednisolone 0.7-l mg/kg/day, with variable tapering to 40 mg, followed by tapering of 4 mg weekly.
Ten of the 22 antibiotic patients (45.5%) and 12 of the 19 steroid patients (63%) obtained clinical remission (Crohn's Disease Activity Index < or = 150) at the end of the 12-wk study (p = NS). Five patients on antibiotics (22.7%) and five patients on steroids (26.3%) were considered treatment failures because of deterioration or persistent symptoms. Six patients receiving antibiotics (27.3%) and two on steroids (10.6%) were withdrawn from the trial because of side effects. One patient on antibiotics was not compliant.
metronidazole and ciprofloxacin could be an alternative to steroids in treating the acute phase of CD.
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