Andrea Mikulits

Long-term success of GUT-directed group hypnosis for patients with refractory irritable bowel syndrome: a randomized controlled trial.

OBJECTIVES:Gut-directed hypnotherapy (GHT) in individual sessions is highly effective in the treatment of irritable bowel syndrome (IBS). This study aimed to assess the long-term effect of GHT in group sessions for refractory IBS.METHODS:A total of 164 patients with IBS (Rome-III-criteria) were screened, and 100 refractory to usual treatment were randomized 1:1 either to supportive talks with medical treatment (SMT) or to SMT with GHT (10 weekly sessions within 12 weeks). The primary end point was a clinically important improvement on several dimensions of daily life (assessed by IBS impact scale) after treatment and 12-month follow-up. The secondary end point was improvement in general quality of life (QOL; Medical Outcome Study Short-Form-36), psychological status (Hospital Anxiety Depression Scale) and reduction of single IBS symptoms. Analysis was by intention to treat.RESULTS:A total of 90 patients received allocated intervention. After treatment, 28 (60.8%) out of 46 GHT patients and 18 (40.9%) out of 44 SMTs improved (absolute difference 20.0%; 95% confidence interval (CI): 0–40.2%; P=0.046); over 15 months, 54.3% of GHT patients and 25.0% of controls improved (absolute difference 29.4%; 95% CI 10.1–48.6%; P=0.004). GHT with SMT improved physical and psychological well being significantly more than SMT alone (P<0.001). Gender, age, disease duration and IBS type did not have an influence on the long-term success of GHT.CONCLUSIONS:GHT improves IBS-related QOL, is superior to SMT alone, and shows a long-term effect even in refractory IBS.

Predictors of indeterminate IFN-γ release assay in screening for latent TB in inflammatory bowel diseases

Eur J Clin Invest 2011; 41 (10): 1071–1076

Long-term outcome in patients with ulcerative colitis treated with intravenous cyclosporine A is determined by previous exposure to thiopurines

BACKGROUND AND AIM Rescue therapy with intravenous cyclosporine A (CsA) helps to avoid colectomy in a substantial proportion of patients with severe ulcerative colitis (UC) but the impact on long-term outcome remains unclear. Therefore, we aimed to define predictive factors for colectomy in patients treated with intravenous CsA for severely active UC. METHODS A retrospective, single-center study with a minimum follow-up of 18 months was performed. RESULTS A total of 64 patients were evaluable (median age 33 years [range 17-80 years], female 54.7%). Median intravenous CsA dose was 4 mg/kg/day (range 2-5mg/kg/day). After a median follow-up of 65 months (range 2-160 months), 19 patients (29.7%) underwent colectomy, 15 within 18 months. Of the various baseline parameters tested, only previous non-response to thiopurine treatment (p=0.006) was associated with an increased risk of colectomy. During 18 months follow-up, thiopurine-naïve patients receiving thiopurine maintenance therapy after intravenous CsA (32/64, 50.0%) underwent colectomy in 12.5% of cases. The colectomy rate was 27.3% among 22 patients previously non-responsive to thiopurines who continued treatment after intravenous CsA, compared to 50.0% in the 10 patients who discontinued thiopurines prior to intravenous CsA or who never received thiopurines (p=0.037). CONCLUSIONS The long-term colectomy rate after intravenous CsA in patients with severely active UC was relatively low in our series compared to the literature. Concomitant treatment with thiopurines was the only predictor for a reduced risk of colectomy.

Retesting for latent tuberculosis in patients with inflammatory bowel disease treated with TNF-α inhibitors

Patients treated with TNF‐α inhibitors (TNFi) are at high risk of reactivation of latent tuberculosis (LTB). Prospective studies on monitoring of TB reactivation and/or infection in this risk group are lacking.

High Risk of Transfusion-induced Alloimmunization of Patients with Inflammatory Bowel Disease

BACKGROUND Anemia is highly prevalent in inflammatory bowel disease patients, and red blood cell transfusion is often indicated already at reproductive age. Both transfusion and pregnancy may induce red cell alloantibodies, potentially complicating further transfusions and pregnancies. As recent evidence suggests that inflammation may promote red cell antibody induction, the alloimmunization risk of these patients after allogenic erythrocyte exposure was investigated. METHODS Red cell alloantibody status and clinical data were analyzed in 193 inflammatory bowel disease patients with a history of transfusion or pregnancy, and compared with transfused controls with noninflammatory diseases (n=357). RESULTS In transfused patients with inflammatory bowel disease, a 2.5-fold-increased red cell antibody prevalence was found (10/119, 8.4%), compared with transfused sex-matched controls with noninflammatory diseases (12/357, 3.4%; P=.023). Patients with inflammatory bowel disease had fewer transfusions (mean 3.0 vs 4.2, P=.003) but higher C-reactive protein levels during transfusion than controls (mean 8.4 vs 5.4 mg/dL, P <.001). The red cell antibodies of inflammatory bowel disease patients were clinically significant, directed against different Rh, Kell, Duffy, or Lutheran blood group antigens, and associated with higher number of transfusions (odds ratio 1.57; 95% confidence interval, 1.03-2.39). Conversely, immunomodulatory therapy during transfusion showed negative association (odds ratio 0.12; 95% confidence interval, 0.02-0.61). Only 1.4% of inflammatory bowel disease patients with pregnancy alone had antibodies. CONCLUSIONS Patients with inflammatory bowel disease exhibited a very high risk of transfusion-induced red cell alloimmunization, possibly potentiated by inflammation. Aside from a restrictive transfusion strategy, the implementation of prophylactic blood group phenotype matching of red cell concentrates (not only for ABO and RhD but also RhCcEe, Kell, Kidd, Duffy) could prevent antibody induction and associated complications in these patients.

The impact of intestinal resection on serum levels of anti‐Saccharomyces cerevisiae antibodies (ASCA) in patients with Crohn’s disease

Aliment Pharmacol Ther 2012; 35: 292–299

P374 Fecal transplantation in patients with moderately to severely chronic active ulcerative colitis (UC)

Background: A diminished biodiversity of the intestinal flora has been reported in patients with IBD. Restoration of a normal flora is being discussed as an alternative treatment approach. Methods: We assessed safety and efficacy of fecal transplantation (FT) in moderately to severely, chronic active patients with UC (n = 5, f/m: 2/3, median Mayo score: 11) refractory to standard therapy. Immunosuppressive therapy was stopped prior FT. Fecal donors were healthy adults with normal bowel function who were screened for enteric pathogens and serologically for viral diseases. Donor stool was diluted in saline and administered via nasojejunal tube and enema. Adverse events and blood tests were regularly obtained during a followup of 12 weeks. H2-glucose breath test was performed to exclude bacterial overgrowth at wk 4 and wk 12 weeks. Clinical activity was assessed according to Mayo Score. Results: Patients completed an antibiotic (n = 5) and probiotic (n = 4) therapy for 5 to 10 days and a single bowel lavage before FT. FT was performed daily for 3 days (n = 4). In one patient there was a gap of 5 weeks between the first and the second FT due to fever >39oC and a >8-fold increase of C-reactive protein (CRP) after first FT. Altogether, median 23.8 g (range:16.7-g-25 g) and 20 g (range: 6 g-21.7 g) stool was administered via nasojejunal tube and enema, respectively. All of the patients reported on worsening of diarrhoea and fever during FT. Additionally, a temporary increase of CRP was observed. In patients (n = 2), who had a temperature >38oC blood cultures were taken, but no bacterial pathogen was detectable. Additionally, flatulance (n = 1) and vomiting (n = 1) were reported. In the follow-up period common cold (n = 3), itchiness (n = 1), erythema (n = 1), paraesthesia on the hip (n = 1), collapse (n = 1), and blisters on the tongue (n = 1) were reported. No serious adverse event occurred. Bacterial overgrowth was not detectable in any patient. In 2 patients a further deterioration of UC was observed. Although the the general well-being improved from poor to very well at week 12 in the other 3 patients, the median total Mayo score improved only from 11 to 9. In one patient there was an improvement of the Mayo endoscopic subscore from 3 to 2. Conclusions: In our experience FT might be safe but activates a temporary systemic immune response. Our preliminary data are less impressive with regard to efficacy after a minimum follow-up of 12 weeks.

Midday and nadir salivary cortisol appear superior to cortisol awakening response in burnout assessment and monitoring

Burnout and work-related stress symptoms of anxiety disorder and depression cause prolonged work absenteeism and early retirement. Hence, reliable identification of patients under risk and monitoring of treatment success is highly warranted. We aimed to evaluate stress-specific biomarkers in a population-based, “real-world” cohort (burnouts: n = 40, healthy controls: n = 26), recruited at a preventive care ward, at baseline and after a four-month follow up, during which patients received medical and psychological treatment. At baseline, significantly higher levels of salivary cortisol were observed in the burnout group compared to the control group. This was even more pronounced in midday- (p < 0.001) and nadir samples (p < 0.001) than for total morning cortisol secretion (p < 0.01). The treatment program resulted in a significant reduction of stress, anxiety, and depression scores (all p < 0.001), with 60% of patients showing a clinically relevant improvement. This was accompanied by a ~30% drop in midday cortisol levels (p < 0.001), as well as a ~25% decrease in cortisol nadir (p < 0.05), although not directly correlating with score declines. Our data emphasize the potential usefulness of midday and nadir salivary cortisol as markers in the assessment and biomonitoring of burnout.

S1126 Immunosuppressive (IS) Therapy Impacts the Results of QuantiFERON® and Tuberculin Skin Test in Routine Screening for Latent Tuberculosis (LTB) in Patients with Inflammatory Bowel Diseases (IBD)

INTRODUCTION: Screening for LTB is mandatory before starting therapy with Tumor Necrosis Factor (TNF) alpha inhibitors. Recently, a whole blood interferon gamma assay (QuantiFERON®) emerged as additional test for screening of LTB usually consisting of tuberculin skin test (TST) and chest X-ray. However, in patients with immunosuppression (IS) both tests might show limitations. AIMS & METHODS: We aimed to compare results from QuantiFERON®, TST and chest X-ray in consecutive IBD patients with or without IS with the indication of anti TNF alpha therapy. Signs indicative of LTB from chest x-ray included granuloma, bihilar lymphadenopathy and pleura scarring. TST was assessed positive if induration ≥5mm appeared after 48-72h of intracutan application of tuberculin /2 units in 0,1ml/ in immunosuppressed and ≥10mm in all other IBD patients. QuantiFERON® was positive if quantitative measurement indicated ≥ 0,35 U/ml. In pts under IS type, dose, and duration of therapy were obtained. RESULTS: In 145 patients all three tests for LTB were performed. QuantiFERON® test failed on samples from 15/145 (10.3%) patients, resulting in 130/145 (89.7%) patients on whom results from all 3 screening tests were available. There were 109 pts (75.2%) with and 36 (24.8%) without IS. Seventy-six patients (52.4%) were under maintenance AZA/6-MP, 49 (33.7%) under steroids ≥10mg daily for ≥ 2weeks and 16 subjects (11%) received infliximab within a median of 8 (6-16) weeks previously. The impact of IS therapy on TST and QuantiFERON® is shown in the table. The median TST induration was 2.11 mm (±5.2) for the entire study population, 2.07 mm (±5) in pts with and 2.22mm in pts without IS (±5.7) (p=0.882), respectively. Among subjects with positive TST median induration was 12.5 mm (±5.3) in IS patients (n=17) and 16mm (±2.4) in pts without IS (n=5, p=0.058). There was a higher rate of positive QuantiFERON® results in patients without IS (p=0.036). CONCLUSION: Our results reveal significant influence of IS on single TST and QuantiFERON® results in IBD patients undergoing screening for LTB and suggest an underestimation of the actual rate of LTB. Therefore, LTB screening might be best performed before IS treatment.