The efficacy and safety of either infliximab or adalimumab in 362 patients with anti-TNF-α naïve Crohn's disease.

BACKGROUND: TNFα antagonists, including infliximab (IFX) and adalimumab (ADA), have revolutionised treatment for Crohn's disease. Studies comparing efficacy in patients with Crohn's disease naïve to TNFα antagonists are lacking. METHODS: Consecutive TNFα antagonist-naïve patients with luminal or perianal Crohn's disease from four tertiary centres in Austria were assessed prospectively for induction and maintenance efficacy, and safety, of either IFX or ADA. RESULTS: In a total of 362 patients, 251 (69.3%) started IFX and 111 (30.7%) started ADA. At baseline, the median Harvey-Bradshaw Index (HBI) score was 8 (range 5-29) and 8 (5-36), and the median C-reactive protein (CRP) was 1.07 (interquartile range (IQR) 1.36) mg/dL and 1.16 (IQR 1.23) mg/dL for IFX and ADA, respectively. At week 12, there was no difference between IFX and ADA among patients with luminal Crohn's disease in clinical remission (IFX 128/204; 62.7% vs. ADA 68/107; 63.6%, P = 0.47), clinical response (IFX 154/204; 75.5% vs. ADA 82/107; 76.6%, P = 0.82) and steroid-free remission (IFX 110/204; 53.9% vs. ADA 61/107; 57%, P = 0.60). At 12 months, there were similar numbers of patients treated with IFX and ADA who maintained clinical remission (IFX 77/154; 50.4% vs. ADA 47/82; 57.3%, P = 0.48) and steroid-free remission (IFX 68/154; 44.3% vs. ADA 44/82; 53.7%, P = 0.16). Baseline CRP >0.7 mg/dL (OR 0.24; 95% CI 0.07-0.77, P = 0.01) was the only predictor of clinical remission at 12 months in patients who did not have escalation of anti-TNFα therapy. CONCLUSION: IFX and ADA appear comparable in clinical outcomes for patients with Crohn's disease who are naïve to TNFα antagonists.

Surgical recurrence after primary ileocolic resection for Crohn's disease.

BACKGROUND: The current study was conducted to assess long-term outcomes after primary ileocolic resection for Crohn's disease (CD) and to identify factors associated with surgical relapse in the era of immunosuppressive medications. METHODS: Data were collected retrospectively on 116 consecutive patients, who underwent primary ileocolic resection for CD at a tertiary referral center between 1997 and 2006. Medical records were reviewed, and the use of immunomodulators was noted. The cumulative probability for a second operation due to recurrent CD was described by Kaplan-Meier curves. RESULTS: Ten patients (8.6 %) developed surgical recurrence after a mean follow-up period of 8.1 (±2.6) years. The percentage of patients not requiring further surgery was 96.5% and 88.0 % at 5 and 10 years, respectively. An urgent indication for surgery was significantly associated with the necessity of repeated intestinal resection (hazard ratio 5.6, 95 % confidence interval 1.2-27.0, p = 0.0145). In addition, postoperative exposure to azathioprine/6-mercaptopurine for more than 3 months decreased the probability of surgical recurrence significantly (hazard ratio 2.5, 95 % confidence interval 0.6-9.9, p = 0.0349). CONCLUSIONS: In contrast to previous studies, we observed a significant low surgical recurrence rate after primary ileocolic resection. Additionally, maintenance treatment with azathioprine/6-mercaptopurine after surgery may reduce the necessity for repeat surgical intervention.

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

BACKGROUND: 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. AIM: To test the conversion and reversion rate of screening tests for latent TB serial tuberculin skin test (TST) and interferon-γ release assay (IGRA) under ongoing TNFi therapy. METHODS: We retested consecutive patients with IBD receiving TNFi therapy for a minimum of 5 months for LTB using IGRA and TST. A detailed patient history and concomitant therapy were recorded for each subject. RESULTS: After a median of 34.9 weeks (20.7­177.7), IGRA was retested in 184/227 patients (81.1%; Crohn's disease n = 139, ulcerative colitis n = 45) still under index TNFi. TST was available in 144/184 subjects (78.2%). The majority of patients were TNFi naïve (147/184, 79.9%). In a subgroup of patients who received isoniazid due to diagnosis of latent TB at baseline (n = 32), 6/13 patients (46.2%) with baseline positive IGRA and 3/22 patients (13.6%) with baseline positive TST reverted to negative at retesting. In patients without diagnosis of LTB at baseline no permanent IGRA conversion was observed, but there were 6/144 (4.2%) TST conversions from negative to positive. No single case of TB reactivation or infection was recorded during the observation period. CONCLUSIONS: During treatment TNF-α inhibitors conversion was observed for tuberculin skin test, but not interferon-γ release assay. As compared with tuberculin skin test, interferon-γ release assay reverted in nearly half of isoniazid-treated patients for latent tuberculosis. However, the fact that patients in whom the interferon-γ release assay test result remained positive did not develop active tuberculosis during follow-up questions the utility of interferon-γ release assay as a monitoring tool during chemoprevention.

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

BACKGROUND: Antibodies to Saccharomyces cerevisiae (ASCA) are highly prevalent in sera of patients with Crohn's disease and have been proposed to identify subgroups of patients with a disabling disease course. AIM: To investigate the impact of intestinal resection on serum levels of ASCA in patients with Crohn's disease and the predictive value of ASCA levels on surgical recurrence. METHODS: Sera from 60 patients who underwent 'curative' intestinal resection due to stricturing and/or penetrating complications were collected preoperatively and during post-operative follow-up (week 2, months 4, 8 and 11 ± 1). Measurement of ASCA IgG and IgA isotypes were performed using ELISA. Re-operation rate was associated with ASCA status and serum levels. RESULTS: At baseline 44/60 (73%) of patients were rated as positive for ASCA IgG, 45/60 (75%) for ASCA IgA and 52/60 (87%) as positive for at least one of both. ASCA serum levels remained stable during first year from resection. After a median of 106 months 10 of 40 (25%) patients with long-term follow-up underwent one or more intestinal re-operations. Neither ASCA positivity nor absolute ASCA serum levels were predictive of surgical recurrence. CONCLUSIONS: Serum ASCA levels remain stable after curative intestinal resection in Crohn's disease. This indicates the persistence of both stimulus and immunological mechanism operative in the production of ASCA even after complete surgical resection of macroscopically inflamed intestinal tissue. After intestinal resection, neither ASCA positivity nor ASCA serum levels predict the risk of surgical recurrence during long-term follow-up.

Anti-Gal titers in healthy adults and inflammatory bowel disease patients.

INTRODUCTION: ALPHA-GAL is a glycoconjugate present on cell membranes of mammals and bacteria but not humans who display anti-Gal antibodies (AB) in high titers provoked by the commensal gut flora. In the present study, we sought to determine the longitudinal course of alpha-Gal specific AB titers of all isotypes over 8 weeks among healthy adult subjects. Furthermore, we hypothesized that inflammatory bowel disease (IBD) patients display increased anti-Gal titers. MATERIALS AND METHODS: We drew serum from healthy probands (n=20) weekly for 8 weeks and obtained plasma samples of from patients suffering from Crohn's disease (n=20) and ulcerative colitis (n=20). We measured anti-Gal ABs of all isotypes and total immunoglobulin (Ig) content using an enzyme-linked immunosorbent assay technique. For statistical evaluation of the longitudinal titers, we calculated confidence intervals for the slopes of a random intercept model, comparing variances between and within the probands. For group comparisons, we performed paired student t-tests and Pearson correlations. RESULTS: Alpha-Gal specific IgG, IgM, IgD, and IgA titers remained unvaried within a narrow range upon longitudinal observation. Most probands did not display alpha-Gal specific IgE ABs. Crohn's disease patients showed highly increased alpha-Gal-specific IgA titers compared with control subjects (P<.01). CONCLUSION: Apart from IgE, alpha-Gal-specific ABs of all isotypes remained constant over longer time periods in healthy subjects. Thus, significant titer changes actually represent increased antigen exposure and a specific anti-alpha-Gal response. Crohn's disease patients display increased anti-Gal IgA titers compared with healthy controls, which reflects a chronically impaired mucosal gut barrier in this patient cohort.

Short-term complications of wide-lumen stapled anastomosis after ileocolic resection for Crohn's disease: who is at risk?

AIM: There is growing evidence that stapled anastomoses are similarly effective compared to hand-sewn anastomoses in Crohn's patients. This study was designed to assess safety and limitations of wide-lumen stapled ileocolic anastomoses. METHOD: All patients with ileocolic resections for Crohn's disease perfomed between 1998 and 2006 were studied. A stapled anastomosis was constructed whenever possible. Potential risk factors for postoperative complications were recorded, retrospectively. Univariate and multivariate analyses were performed. RESULTS: In 209 out of 220 cases (95%, 132 primary operations) stapled anastomoses were performed. Eleven patients underwent a hand-sewn anastomosis owing to massive bowel dilatation (n = 7) or increased wall thickness (n = 4). There were 10 major (4.5%; surgical: 8, medical: 2) complications including two anastomotic leaks and one anastomotic bleed (all from stapled anastomoses) and one death not related to the anastomosis. Minor complications occurred in 25 patients. In multivariate analysis, major surgical postoperative complications were significantly associated with a low level of albumin (P = 0.0113) and previous resections for Crohn's disease (P = 0.0144). CONCLUSION: Stapled ileocolic anastomosis was safe in the majority of Crohn's patients. The most important limitation was technical impracticability. A low level of albumin and a history of previous resection increased the risk of postoperative complications.

Physical symptoms in post-traumatic stress disorder.

Physical complaints are recognised accompaniments of Post-Traumatic Stress Disorder (PTSD). This study investigates the reporting of physical complaints in a treatment-naive sample of fire-fighters with and without PTSD. Statistically higher rates of cardiovascular, respiratory, musculoskeletal and neurological symptoms were reported in the PTSD group. Possible explanations are discussed, with an exploration of the contribution of arousal, disordered information processing, dissociation, comorbid diagnoses and premorbid personality. The role of the original stressor and sociocultural issues are explored.

Multiple diagnoses in posttraumatic stress disorder in the victims of a natural disaster.

A population of the fire fighters who had been exposed to a natural disaster were screened using the General Health Questionnaire 4, 11, and 29 months after a natural disaster. On the basis of these data, a high-risk group of subjects who had scored as cases and probable cases and a symptom-free comparison group were interviewed using the Diagnostic Interview Schedule 42 months after the disaster. The prevalence of posttraumatic stress disorder (PTSD), affective disorders, and anxiety disorders was examined. Only 23% of the 70 subjects who had developed a PTSD did not attract a further diagnosis, with major depression being the most common concurrent disorder. Comorbidity appeared to be an important predictor of chronic PTSD, especially with panic disorder and phobic disorders. The subjects who had only a PTSD appeared to have had the highest exposure to the disaster. Adversity experienced both before and after the disaster influenced the onset of both anxiety and affective disorders.

A group method for learning about psychiatric research.

Psychiatric trainees in their final year of training met fortnightly with an experienced psychiatric researcher. A group format was used to facilitate the development of skills employed in psychiatric research. Various exercises, including conducting a research project during the group sessions, were undertaken. This report highlights certain issues that may inhibit clinicians from undertaking research projects. It is presented from both the group leader's and the participants' perspectives.