Magnetic resonance enterography changes after antibody to tumor necrosis factor (anti-TNF) alpha therapy in Crohn's disease: correlation with SES-CD and clinical-biological markers.

BACKGROUND: In recent years, the use of MRI in patients with Crohn's disease (CD) has increased. However, few data are available on how MRI parameters of active disease change during treatment with anti-TNF and whether these changes correspond to symptoms, serum biomarkers, or endoscopic appearance. The aim of this study was to determine the changes over time in MRI parameters during treatment with anti-TNF in patients with CD, and to verify the correlation between MRI score, endoscopic appearance and clinical-biological markers. METHODS: We performed a prospective single centre study of 27 patients with active CD (18 males and 9 females; median age of 27,4 ys; age range, 19-49). All patients underwent ileocolonoscopy and MRI at baseline and 26 weeks after anti-TNF therapy. Endoscopic severity was graded according to the Simple Endoscopic Score for Crohn's Disease (SES-CD) and Magnetic Resonance Index of Activity (MaRIA) was calculated. Patients underwent clinical evaluation (CDAI) and the C-reactive protein (CRP) level was measured. The associations between variables were assessed with Pearson's bivariate correlation analysis. RESULTS: A total of 135 intestinal segments were studied. The median patient age was 27,4 years, 67 % were male and the mean disease duration was 6,1 years. For induction of remission, 18 patients were treated with infliximab and 9 with adalimumab. The mean SES-CD and MaRIA scores significantly changed at week 26 (SES-CD: 14,7 ± 8,9 at baseline vs. 4,4 ± 4,6 at 26 weeks - p < 0.001; MaRIA: 41,1 ± 14,8 at baseline vs. 32,8 ± 11,7 at 26 weeks - p < 0.001). Also the CDAI and serum levels of CRP decreased significantly following treatment (p < 0.001). The overall MaRIA correlated with endoscopic score and with clinical activity (CDAI) both at baseline and at week 26 (p < 0.05). The correlation between overall MaRIA and CRP was significant only at week 26 (p < 0.001). CONCLUSIONS: The MaRIA has a good correlation with SES-CD, a high accuracy for prediction of endoscopic mucosal healing and is a reliable indicator to monitor the use of TNF antagonists in patients with CD.

Helicobacter pylori vacA arrangement and related diseases: a retrospective study over a period of 15 years.

Peptic ulcer disease incidence is decreasing. Both s1m1 and s1m2 vacA gene combinations of Helicobacter pylori have been associated with the development of major gastroduodenal diseases. This study assessed whether H. pylori vacA gene arrangement changed over 15 years in a Southern Italy area. H. pylori-positive patients observed in January-June 1989 and January-June 2005 were selected. Histological specimens were retrieved to extract DNA for vacA arrangement characterization (mid-m and peptide signal-s regions) by using the polymerase chain reaction. Fifty-nine patients in the first period and 56 matched patients in the second period were evaluated. A correlation between s1 presence and intestinal metaplasia at histology was found. Overall, the s1m1 combination increased (P < 0.01) and s2m2 decreased (P < 0.001) during the study period. In detail, s1m1 (P < 0.05) and s1m2 (P < 0.01) increased, and s2m2 decreased (P < 0.001) in dyspeptic patients, while only s1m1 increased (P < 0.01) in peptic ulcer patients. Finally, few cases of s2m1 combination in both series were found. Our results show some unexpected aspects that require confirmation. In detail, the increased prevalence of potential more virulent H. pylori strains contrasts with peptic ulcer incidence reduction.

Prevalence of primary clarithromycin resistance in Helicobacter pylori strains over a 15 year period in Italy.

OBJECTIVES: The frequency of primary clarithromycin resistance in Helicobacter pylori strains is increasing worldwide, and its presence significantly reduces the treatment efficacy of infection. This study aimed to evaluate whether the progression of the prevalence of clarithromycin resistance over a 15 year period has increased and whether a possible change in the distribution of the three most frequent point mutations, which account for the large majority of clarithromycin resistance cases, has taken place. METHODS: Antral biopsies of consecutive H. pylori-positive patients observed between January 1989 and December 1990 and between January 2004 and December 2005 were retrieved. A TaqMan real-time PCR was performed in all cases to assess point mutations involved. RESULTS: Primary clarithromycin resistance was assessed for 147 patients observed in the first period 1989-90 and 178 cases observed in the second period 2004-05. The overall frequency of clarithromycin resistance increased from 10.2% (15 patients) to 21.3% (38 patients) during the study period (P = 0.01). The increase was more evident in females [4 out of 55 patients (7.2%) versus 24 out of 103 patients (23.3%); P = 0.01] and in non-ulcer dyspepsia patients [13 out of 106 patients (12.2%) versus 37 out of 140 (26.4%) patients; P = 0.009]. A2143G was the most frequent point mutation observed in both study periods, and its prevalence rate remained unchanged [11 out of 15 (73.3%) patients versus 27 out of 38 (71%) patients; P = 1]. CONCLUSIONS: A 2-fold increase in primary clarithromycin resistance in H. pylori strains occurred during the last 15 years in Italy. A2143G remains the most prevalent point mutation involved, thus suggesting that new therapeutic strategies are needed.

Onset of liver damage after a single administration of infliximab in a patient with refractory ulcerative colitis.

We report the case of a patient with refractory ulcerative colitis who developed cholestatic acute liver damage after a single infusion of infliximab. Unusual aspects of this case were the early onset (after the first administration) of liver damage and the absence of antinuclear antibodies, alcohol intake, hepatotoxic drugs and all known viral and metabolic causes of hepatic injury. Moreover, no serological or morphological findings of primary sclerosing cholangitis were observed. The patient's liver damage resolved spontaneously within 6 weeks. Although a direct relationship between administration of infliximab and onset of acute liver damage could not be definitely established, our case suggests that infliximab may induce direct liver damage, the course of which is similar to acute cholestatic hepatitis and resolves following withdrawal of the drug.

Claritromycin resistance and Helicobacter pylori genotypes in Italy.

The relationship between H. pylori clarithromycin resistance and genetic pattern distribution has been differently explained from different geographic areas. Therefore, we aimed to assess the clarithromycin resistance rate, to evaluate the bacterial genetic pattern, and to search for a possible association between clarithromycin resistance and cagA or vacA genes. This prospective study enrolled 62 consecutive H. pylori infected patients. The infection was established by histology and rapid urease test. Clarithromycin resistance, cagA and vacA status, including s/m subtypes, were assessed on paraffin-embedded antral biopsy specimens by TaqMan real time polymerase chain reaction (PCR). Primary clarithromycin resistance was detected in 24.1 % of cases. The prevalence of cagA was 69.3 %, and a single vacA mosaicism was observed in 95.1 % cases. In detail, the s1m1 was observed in 23 (38.9 %) patients, the s1m2 in 22 (37.2 %), and the s2m2 in 14 (23.7 %), whereas the s2m1 combination was never found. The prevalence of cagA and the vacA alleles distribution did not significantly differ between susceptible and resistant strains. Primary clarithromycin resistance is high in our area. The s1m1 and s1m2 are the most frequent vacA mosaicisms. There is no a relationship between clarithromycin resistance and bacterial genotypic pattern and/or cagA positivity.