Introduction
Crohn’s disease (CD) is a progressive inflammatory disease affecting the entire gastrointestinal tract. The need for a definitive stoma (DS) is considered as the ultimate phase of ...damage. It is often believed that the risk of further disease progression is small when a DS has been performed.
Aims
The goals of the study were to establish the rate of CD recurrence above the DS and to identify predictive factors of CD recurrence at the time of DS.
Methods
We retrospectively reviewed all medical records of consecutive CD patients having undergone DS between 1973 and 2010. We collected clinical data at diagnosis, CD phenotype, treatment, and surgery after DS and mortality. Stoma was considered as definitive when restoration of continuity was not possible due to proctectomy, rectitis, anoperineal lesions (APL), or fecal incontinence. Clinical recurrence (CR) was defined as the need for re-introduction or intensification of medical therapy, and surgical recurrence (SR) was defined as a need for a new intestinal resection.
Results
Eighty-three patients (20 males, 63 females) with a median age of 34 years at CD diagnosis were included. The median time between diagnosis and DS was 9 years. The median follow-up after DS was 10 years. Thirty-five patients (42%) presented a CR after a median time of 28 months (2–211) and 32 patients (38%) presented a SR after a median time of 29 months (4–212). In a multivariate analysis, APL (HR = 5.1 (1.2–21.1),
p
= 0.03) and colostomy at time of DS (HR = 3.8 (1.9–7.3),
p
= 0.0001) were associated factors with the CR.
Conclusion
After DS for CD, the risk of clinical recurrence was high and synonymous with surgical recurrence, especially for patients with APL and colostomy.
Infliximab and adalimumab are increasingly used to prevent postoperative recurrence in Crohn's disease patients. The impact of previous exposure to one or more anti-tumour necrosis factor TNF agents ...before surgery on the efficacy of anti-TNF therapy on postoperative recurrence is unknown.
We performed a retrospective analysis of Crohn's disease patients who underwent surgical bowel resection with anastomosis and prophylactic treatment with anti-TNF therapy between January 2005 and June 2013.
A total of 57 consecutive Crohn's disease patients with bowel resection and anastomosis followed by prophylactic treatment with anti-TNF were included; 21 37% and 24 42% patients had a previous exposure to one and more than one anti-TNF agents, respectively; 39 patients 68% had a surveillance colonoscopy. Cumulative rates of postoperative endoscopic recurrence at 2 years were 45.5% 26.6-69.6% in patients exposed to two or more anti-TNFα as compared with 29.1% 11.5-48.1% in patients exposed to one or to zero anti-TNFα before surgery p = 0.07. Cumulative rates of clinical recurrence at 1 year were 21.6% 9.6-44.4% in patients exposed to two or more anti-TNFα as compared with 6.9% 1.8-25.1% in patients exposed to zero or one anti-TNFα before surgery p = 0.02. Multivariable analysis identified smoking and previous exposure to two or more anti-TNFα as risk factors for Crohn's disease clinical or endoscopic postoperative recurrence (hazard ratio HR = 3.17; 95% confidence interval CI: 1.3-7.8, p = 0.01 and HR = 4.2; 95% CI: 1.8-10.2, p = 0.001, respectively).
Previous exposure to two or more anti-TNF agents was associated with a higher risk of postoperative recurrence in Crohn's disease patients.
To describe long-term postoperative evolution of pediatric-onset Crohn's disease (CD) and identify predictors of outcome we studied a population-based cohort (1988-2004) of 404 patients (0-17 years), ...of which 130 underwent surgery.
Risks for a second resection and first need for immunosuppressors (IS) and/or biologics were estimated by survival analysis and Cox models used to determine predictors of outcome. Impact of time of first surgery on nutritional catch-up was studied using regression.
In all, 130 patients (70 females) with a median age at diagnosis of 14.2 years (interquartile range: 12-16) were followed for 13 years (9.4-16.6). Probability of a second resection was 8%, 17%, and 29% at 2, 5, and 10 years, respectively. In multivariate analysis, age <14, stenosing (B2) and penetrating (B3) behaviors and upper gastrointestinal location (L4) at diagnosis were associated with an increased risk of second resection. Probability of receiving IS or biologics was 18%, 34%, and 47% at 2, 5, and 10 years, respectively. In multivariate analysis, L4 was a risk factor for requiring IS or biologics, while surgery within 3 years after CD diagnosis was protective. Catch-up in height and weight was better in patients who underwent surgery within 3 years after CD diagnosis than those operated on later.
In this pediatric-onset CD study, mostly performed in a prebiologic era, a first surgery performed within 3 years after CD diagnosis was associated with a reduced need for IS and biologics and a better catch-up in height and weight compared to later surgery.
Pegylated interferon α-2a (Peg-IFN-α) represents a therapeutic alternative to the prolonged use of nucleos(t)ide analog (NA) in chronic hepatitis B (CHB) infection. The mechanisms leading to a ...positive clinical outcome remain unclear. As immune responses are critical for virus control, we investigated the effects of Peg-IFN-α on both innate and adaptive immunity, and related it to the clinical evolution. The phenotypic and functional features of the dendritic cells (DCs), natural killer (NK) cells and HBV-specific CD4/CD8 T cells were analyzed in HBeAg-negative CHB patients treated for 48-weeks with NA alone or together with Peg-IFN-α, before, during and up to 2-years after therapy. Peg-IFN-α induced an early activation of DCs, a potent expansion of the CD56bright NK subset, and enhanced the activation and functionality of the CD56dim NK subset. Peg-IFN-α triggered an increase in the frequencies of Th1- and Th17-oriented HBV-specific CD4/CD8 T cells. Peg-IFN-α reversed the unresponsiveness of patients to a specific stimulation. Most of the parameters returned to baseline after the stop of Peg-IFN-α therapy. Peg-IFN-α impacts both innate and adaptive immunity, overcoming dysfunctional immune responses in CHB patients. These modulations were not associated with seroconversion, which questioned the benefit of the add-on Peg-IFN-α treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
Identification of children with Crohn's disease (CD) at high risk of disabling disease would be invaluable in guiding initial therapy. Our study aimed to identify predictors at diagnosis ...of a subsequent disabling course in a population‐based cohort of patients with pediatric‐onset CD.
Methods:
Among 537 patients with pediatric CD diagnosed at <17 years of age, 309 (57%) with 5‐year follow‐up were included. Clinical and demographic factors associated with subsequent disabling CD were studied. Three definitions of disabling CD were used: Saint‐Antoine and Liège Hospitals' definitions and a new pediatric definition based on the presence at maximal follow‐up of: 1) growth delay defined by body mass index (BMI), weight or height lower than −2 SD Z score; and 2) at least one intestinal resection or two anal interventions. Predictors were determined using multivariate analyses and their accuracy using the kappa method considering a relevant value ≥0.6.
Results:
According to the Saint‐Antoine definition, the rate of disabling CD was 77% and predictors were complicated behavior and L1 location. According to the Liège definition, the rate was 37% and predictors included behavior, upper gastrointestinal disease, and extraintestinal manifestations. According to the pediatric definition, the rate of disabling CD was 15%, and predictors included complicated behavior, age <14, and growth delay at diagnosis. Kappa values for each combination of predictors were, respectively, 0.2, 0.3, and 0.2 and were nonrelevant.
Conclusions:
Clinical parameters at diagnosis are insufficient to predict a disabling course of pediatric CD. More complex models including serological and genetic biomarkers should be tested. (Inflamm Bowel Dis 2012;)
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