High prevalence of viable Mycobacterium avium subspecies paratuberculosis in Crohn's disease

AIM:To examine the detection rate of viable Mycobacterium avium subspecies paratuberculosis(MAP) in patients with inflammatory bowel disease [Crohn's disease(CD) and ulcerative colitis(UC)].METHODS:Thirty patients with CD(15 with at least one NOD2/CARD15 mutation),29 with UC,and 10 with no inflammatory bowel disease(IBD).were tested for MAP by polymerase chain reaction(specific IS900 fragment) and blood culture.RESULTS:MAP DNA was detected in all original blood samples and 8-wk blood cultures(CD,UC and non-IBD).Positive MAP DNA status was confirmed by dot blot assays.All 69 cultures were negative by acid-fast Ziehl-Neelsen staining.Viable MAP,in spheroplast form,was isolated from the 18-mo blood cultures of all 30 CD patients,one UC patient,and none of the non-IBD controls.No association was found between positive MAP cultures and use of immunosuppressive drugs or CDassociated single nucleotide polymorphisms.CONCLUSION:MAP is widely present in our area and MAP DNA can be recovered from the blood of CD,UC and non-IBD patients.However,MAP spheroplasts were only found in CD patients.

Mycobacterium avium subspecies paratuberculosis and its relationship with Crohn's disease

The hypothesis postulating that Mycobacterium avium paratuberculosis(MAP) is the cause of Crohn's disease(CD) has been circulating for many years.Advances in molecular techniques,such as polymerase chain reaction and culture methods,have enabled researchers to demonstrate that there is an association between MAP and CD.Recently,genome-wide association studies have identified novel susceptibility genes for CD,which are critical for generation of an adaptive immune response that is protective against intracellular pathogens,including M.tuberculosis infection.However,the role of MAP as a cause of CD suffered a setback with the report that administration of antimycobacterial therapy failed to lead to a sustained response in CD patients.Accordingly,this review sought neither to confirm nor refute this,but instead to survey recent literature on the role of MAP in CD.

IBD5 polymorphisms in inflammatory bowel disease: Association with response to infliximab

AIM: Inflammatory bowel diseases (IBD) are multifactorial pathologies of unknown etiology. One susceptibility locus,IBD5, has been mapped to chromosome 5q31. We analyzed our Spanish cohorts of Crohn's disease (CD)and ulcerative colitis (UC) patients to determine whether this locus is associated with IBD, and to ascertain the main clinical phenotype influenced by this risk factor. The kind of interaction, either genetic heterogeneity or epistasis, between this IBD5 susceptibility region and the NOD2/CARD15 gene mutations was studied as well.Finally, ve assessed whether this locus can predict response to infliximab therapy.METHODS: A case control study was performed with 274CD and 211 UC patients recruited from a single center and 511 healthy ethnically matched controls. Two polymorphisms were genotyped in the IBD5 locus and three in the CARD15/NOD2 gene.RESULTS: Our results evidence association only with CD especially with the fistulizing phenotype and in the absence of NOD2/CARD15 variants (mutant allele frequency in patients vscontrols: OR = 2.03, 95% CI = 1.35-3.06,P＜0.01). The frequency of the IBD5 homozygous mutant genotype significantly increased in CD patients lacking response to infliximab (RR = 3.88, 95% CI = 1.18-12.0,P＜0.05). UC patients overall do not show association with 5q31 polymorphisms, although a similar trend to the one observed in CD is found within the worse prognosis group.CONCLUSION: The IBD5 variants may enhance an individual carrier's risk for CD, mainly in the absence of the NOD2/CARD15 mutations and in fistulizing patients.The data presented suggest the potential role of the 5q31polymorphisms as markers of response to infiiximab.

Need for infliximab dose intensification in Crohn's disease and ulcerative colitis

AIM: To compare the need for infliximab dose intensification in two cohorts of patients with Crohn's disease(CD) or ulcerative colitis(UC).METHODS: Single centre, uncontrolled, observational study. Consecutive patients with CD and UC who responded to infliximab induction doses were included. Data collected in a prospectively maintained database were retrospectively analysed. Differences in the rates of dose intensification per patient-month and the intensification-free survival time were compared. We also evaluated the interval between the first infliximab induction dose and the first infliximab escalated dose. The weight-adjusted infliximab administration costs were also calculated.RESULTS: Fifty nine patients with CD and 38 patients with UC were enrolled. The rate of intensification per patient-month was 3.9% for UC and 1.4% for CD(P = 0.005). The median time from baseline to intensification was significantly shorter in UC compared to CD [6.6 mo(IQR: 4.2-9.5 mo) vs 10.7 mo(IQR: 8.9-11.7 mo), P = 0.005]. In the survival analysis, the cumulative probability of avoiding infliximab dose intensification was significantly higher in CD(P = 0.002). In the multivariate analysis, disease(UC vs CD) was the only factor significantly associated with dose intensification. The infiximab administration costs during the first year were significantly higher for UC compared to CD(mean ± SD 234.9 ± 53.3 Euros/kg vs 212.3 ± 15.1 Euros/kg, P = 0.03).CONCLUSION: The rate of infliximab dose intensification per patient-month is significantly higher in UC patients. The infliximab administration costs are also significantly higher in patients with UC.

Advantages of early cholecystectomy in clinical practice of a terciary care center

BACKGROUND:Despite a number of studies show the superiority of early over delayed cholecystectomy in the treatment of acute cholecystitis,there is still controversy over the time for intervention.This study aimed to assess the use of early versus delayed cholecystectomy for the treatment of acute cholecystitis in terms of complications,conversion to open surgery and mean hospital stay.METHOD:We collected patients with acute cholecystitis treated at a referral center for a year,and retrospectively analyzed the chosen therapeutic approach,the percentage of conversion of early cholecystectomy to open surgery,appearance of surgical complications,and mean hospital stay.RESULTS:The study included 117 patients,44 women and 73 men,who had a mean age of 67.36±15.74 years.Early cholecystectomy was chosen in 31(26.5%) and delayed cholecystectomy in 74 patients(63.2%).Of the 74 patients,28(37.8%) required emergency performance of delayed cholecystectomy,and 19(25.7%) had not undergone surgery by the end of the study.While no differences were observed between early and delayed cholecystectomy in terms of surgical complications and conversion to open surgery,mean hospital stay was nevertheless significantly shorter in the early versus the delayed cholecystectomy group(8.32±4.98 vs 15.96±8.89 days).CONCLUSION:Under the routine working conditions of a hospital that is neither specially dedicated to the surgical treatment of acute cholecystitis nor provided with specific management guidelines,early cholecystectomy can reduce the hospital stay without increase of the conversion rate or complications.