Golimumab improves health-related quality of life of patients with moderate-to-severe ulcerative colitis: Results of the go-care study.

BACKGROUND: In recent years, improvement of Health-Related Quality of Life (HRQoL) in Ulcerative colitis (UC) has become a relevant measure for treatment efficacy. METHODS: We report results from a multicenter prospective study in Italy investigating HRQoL in adult patients with UC treated with golimumab (GLM). Patients who had shown clinical response after a 6-week induction phase (w0), were followed for an additional 48 weeks (w48) (total 54-week treatment). RESULTS: Of the 159 patients enrolled 90 completed the study. Compared to values at the beginning of treatment (n = 137), significant improvements were observed for mean total Inflammatory Bowel Disease Questionnaire (IBDQ) scores at w0 (168.5) and w48 (181.7). Patients with baseline PMS above the median tended to have greater improvements in IBDQ at w0 (OR 2.037, p = 0.033) and w48 (OR 3.292, p = 0.027). Compared to beginning of GLM treatment, the mean Full Mayo Score (FMS) decreased by 5.9 points at w48, while mean Partial Mayo Score (PMS) decreased by 3.9 points at w0 and by 4.9 points at w48. CONCLUSIONS: GLM improved HRQoL, disease activity and inflammatory biomarkers in UC patients with moderate-to-severely active disease. The greater the burden of disease activity at baseline, the greater the improvement of HRQoL after 24 and 48 weeks of treatment.

Diagnostic interobserver variability in Crohn's disease- and ulcerative colitis-associated dysplasia: a multicenter digital survey from the IG-IBD Pathologists Group.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis, two forms of inflammatory bowel disease (IBD), are chronic and relapsing conditions of the gastrointestinal tract both characterized by long lasting chronic inflammation and increased risk of dysplasia and colorectal cancer (CRC). The aim of our study was to evaluate the interobserver agreement about IBD-associated dysplasia among pathologists belonging to the Italian Group for Inflammatory Bowel Diseases (IG-IBD P). METHODS: The present multicenter survey was performed using telepathology, supported by an open source E-learning platform. Biopsy specimens from 30 colonoscopies and from 20 patients were included. The glass slides of any case, including clinical and endoscopic data, were digitalized and uploaded on the E-learning platform. All the digital slides were grouped in 54 diagnostic "blocks". Blinded histopathological evaluation on all the digital slides was performed by 20 gastrointestinal pathologists. Closed-ended questions about (1) the occurrence of IBD; (2) the classification of IBD (as UC or CD); (3) the presence of active versus quiescent disease; (4) the presence of dysplasia; (5) the possible association of dysplasia with the sites of disease (dysplasia-associated lesion or mass-DALM vs adenoma-like mass-ALM); (6) the grading of dysplasia according to the ECCO guidelines (negative, indefinite, low grade, high grade categories) and (7) the presence of associated serrated features, were proposed in each case. Inter-observer agreement was evaluated by mean agreement percentage and kappa statistic, when suitable. RESULTS: The diagnosis of IBD was confirmed in 19 of 20 patients, 17 of 19 being classified as UC, 2 as CD. The mean interobserver agreement percentages about (1) the evidence of IBD, (2) the presence of either UC or CD and (3) the activity grading resulted to be 80%, 69% and 86%, respectively. Dysplasia was detected in 8/20 patients, with moderate agreement between pathologists (mean 72%, k 0.48). Particularly, low grade dysplasia was found in 13 biopsies (combined k 0.38), whereas high grade dysplasia in 8 (combined k 0.47). When the endoscopic and histopathological data were combined, features consistent with DALM were found in 6 of 20 patients with low grade dysplasia and those consistent with ALM in 2 patients with low grade dysplasia in a single biopsy (mean agreement: 86%). An associated serrated pattern was discovered in 4 patients (7 biopsies). CONCLUSIONS: Our study showed moderate interobserver agreement about the histopathological detection and classification of IBD-associated dysplasia. Further efforts should be undertaken to integrate the histopathological data with both the ancillary tests and molecular investigations.

Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease: Results from the Multicenter European TEDDY Study.

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.

Systematic review with meta-analysis: post-operative complications and mortality risk in liver transplant candidates with obesity.

BACKGROUND: International guidelines rate class III (morbid) obesity (body mass index [BMI]≥40 kg/m2 ) as a relative contraindication for liver transplantation (LT) requiring further research. Moreover, data on the mortality risk in candidates with a BMI: 30-34.9 and 35-39.9 kg/m2 (class I and class II obesity, respectively) are weak. AIM: To compare post-operative complications and mortality risks in all obese candidates vs candidates with a BMI: 18.5-29.9 (normal/overweight) assumed as controls. METHODS: We searched the Cochrane library, PubMed, Scopus, Web-of-Science and article reference lists, restricted to the English language, and selected cohort studies analysing the following outcomes: all-causes mortality (at 30 days, 1-2-3-5 years), post-operative and cardiopulmonary complications, hospital and intensive care unit (ICU) length of stay. Two reviewers independently extracted the studies data and a third one resolved discrepancies. RESULTS: Twenty-four studies comprising 132 162 patients met the inclusion criteria. As compared to controls, mortality risk was increased at all time-periods (except at 3 years) for a BMI≥40, at 30 days for a BMI: 30-34.9 and in none of the considered time-periods for a BMI: 35-39.9. Post-operative complications were significantly higher for a BMI>30 and 30-34.9. Due to the shortage/absence of data, we evaluated cardiopulmonary complications, hospital and ICU length of stay only in the BMI≥30 category. In these patients, only cardiopulmonary complications were increased as compared to controls. CONCLUSIONS: Morbid obesity has an impact on patients' survival after LT. However, since even a BMI>30 increases post-transplant complications, new strategies should be included in the LT programme to favour weight loss in all obese candidates.

Small intestinal bacterial overgrowth and celiac disease: A systematic review with pooled-data analysis.

BACKGROUND: A link between small intestinal bacterial overgrowth (SIBO) and celiac disease (CD) has been hypothesized. METHODS: Literature search was performed in main medical databases. Methods of analysis/inclusion criteria were based on Preferred Reporting Items for Systematic reviews and Meta-Analyses recommendations. The end-point was to estimate, by a pooled-data analysis, SIBO prevalence in CD. Proportions/percentages and their 95% confidence intervals (CI) were calculated by inverse variance method, whereas odd ratios (OR) and their 95% CI were estimated, where available, based on the Mantel-Haenszel method. Data were entered into the RevMan 5.3 software. KEY RESULTS: Eleven articles fulfilled considered criteria. The pooled mean prevalence of SIBO in CD was 20% (95% CI of 10%-30%). In comparison to asymptomatic controls, CD was associated to higher risk of SIBO, with an OR of 10.52 (95% CI 2.69-41.21, P=.0007). Jejunal aspirate culture assessed SIBO prevalence of 11% (95% CI 3%-19%) in CD, whereas breath tests detected a higher value (23%, 95% CI 10%-37%). The pooled prevalence of SIBO in CD patients who were symptomatic despite a GFD was 28% (95% CI 10%-47%), higher than in asymptomatic celiac patients (pooled prevalence of 10%, with a 95% CI of 3%-16%), despite not statistically significant (P=.06). When GFD-unresponsive CD was defined only by clinical persistence of symptoms, the prevalence of SIBO was higher than in the case of villous atrophy association (31% vs 16% P=.33). CONCLUSIONS: The heterogeneity of available studies may not support a relationship SIBO-CD. Nevertheless, SIBO could be more common in CD when symptoms do not improve after GFD.

Sequential vs. prolonged 14-day triple therapy for Helicobacter pylori eradication: the meta-analysis may be influenced by 'geographical weighting'.

BACKGROUND: Sequential therapy is a first-line regimen obtaining satisfactory Helicobacter pylori eradication. Triple therapy prolongation improves the success rate even if a recent meta-analysis showed satisfying results only for the 14-day regimen. Studies from Africa and North America were unavailable in previous meta-analyses. AIM: To perform a meta-analysis comparing sequential vs. prolonged 14-day triple therapy with regard to 'geographic weighting' by considering subgroups analysis according to metronidazole/clarithromycin low and high resistance areas. METHODS: Based on PRISMA recommendations, we considered all first-line clinical studies from 2003 to November 2014. Randomised clinical trials (RCTs) were included by a search on PubMed, MEDLINE, Science Direct, EMBASE. Data on eradication rates were expressed as ITT. Risk ratio (RR), pooled RR and 95% confidence intervals were calculated by the Mantel-Haenszel method. Data were entered into RevMan 5.2 software (Nordic Cochrane Centre) using a random-effects model. RESULTS: Databases identified 194 studies; seven met the inclusion criteria. Overall results showed a similar effectiveness of the two regimens considered (RR = 0.99; 95% CI = 0.94-1.05; p = 0.75). In areas with high resistance to clarithromycin, sequential was superior to 14-day triple therapy (RR = 0.95; 95% CI = 0.90-1.00; p = 0.03). In areas with high metronidazole resistance, sequential and 14-day triple therapy were equivalent (RR = 0.99; 95% CI = 0.91-1.08; p = 0.82). CONCLUSIONS: 'Geographic weighting' could be the main factor affecting the lack of differences between sequential and 14-day triple therapy outcomes.

Anti-tumor necrosis factor treatment in occult hepatitis B virus infection: a retrospective analysis of 62 patients with psoriatic disease.

One of the problems possibly related to the use of biological agents targeting tumor necrosis factor (TNF)-alpha is the increased risk of infections, including the activation of hepatitis B virus (HBV). HBV activation can occur in carriers of hepatitis B surface antigen (HBsAg), but the risk may also involve the HBsAg-negative (anti-HBc ± anti-HBs) occult carriers. Precise data on the safety of anti-TNF and/or other immunosuppressive drugs in HBV occult carriers are not available. We performed a retrospective analysis of 62 psoriatic patients with occult HBV infection treated with anti-TNF biological agents over a period of approximately 4 years: 44 subjects were treated with etanercept, 8 with infliximab and 10 with adalimumab. During the observational treatment period, no signs of HBV activation were observed. Only in one patient the reappearance of HBsAg, without detectable HBV-DNA, was noted before retreatment with etanercept and after 10 months from discontinuation of the previous course. In this patient etanercept was re-administered in association with lamivudine without any adverse event. Our results suggest the overall safety of treatment with anti-TNF drugs in HBV occult carriers, although a careful and constant monitoring of virological markers is required in such patients during treatment with anti-TNF drugs in order to have an early recognition of viral reactivation.

Recurrent peptic ulcer disease in a pediatric patient with type 1 neurofibromatosis and primary ciliary dyskinesia.

Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder with characteristic features of skin and central nervous system involvement. Gastrointestinal complications are rare, especially during childhood. In adults, only two cases of peptic ulcer have been reported in neurofibromatosis, both due to Zollinger-Ellison syndrome. Peptic ulcer disease (PUD) may be primary or secondary in nature and it may be life threatening in the acute phase due to the risk of perforation. A case of recurrent gastrointestinal hemorrhage in a child with systemic neurofibromatosis and primary ciliary dyskinesia (PCD) is presented. The upper gastrointestinal endoscopy revealed the presence of multiple gastric ulcers. The ulcers scarred after the long-term administration of a proton pump inhibitor (PPI), but recurred after the suspension. Laboratory and imaging studies excluded Zollinger-Ellison syndrome and other known causes of PUD, suggesting a potential role of neurofibromatosis itself and primary ciliary dyskinesia in developing of recurrent PUD. As early diagnosis of PUD is vital for patient survival, this case report highlights the possible association of neurofibromatosis and PCD with this condition, responsive to PPI therapy and the potential need of gastric protection before complications arise.

Perfusion MRI in the evaluation of cerebral blood volume and mean transit time in untreated and recurrent glioblastomas.

Perfusion MRI by means of dynamic contrast-enhanced T2-weighted MR imaging allows quantitative analysis of cerebral blood volume (CBV) and mean transit time (MTT) in intra-axial brain tumors. Our aim was to compare recurrent glioblastomas to untreated glioblastomas, determining if there are differences in perfusion parameters between the two groups. Serial MR examinations were performed in 26 patients with glioblastoma histologically demonstrated before surgical resection and in 19 patients with recurrent glioblastoma after surgery and radiotherapy. Tumor recurrence was established using both histological and clinical criteria. Normalized CBV and MTT ratios were considered and compared between the two groups. A statistically significant difference, both in average and maximum normalized CBV ratios between the two groups was found. In particular, average and maximum normalized CBV ratios were greater in untreated than in recurrent glioblastomas. On the contrary, average and maximum normalized MTT ratios were greater in the recurrent glioblastomas, than in untreated tumors. Perfusion MRI by means of dynamic contrast-enhanced T2-weighted MR imaging is a valuable adjunct to conventional MR imaging in assessing different hemodynamic features between untreated and recurrent glioblastomas. In particular, tumor recurrence must be suspected even if the average and maximum normalized CBV ratios are far below those of untreated glioblastomas. In addition, increased average and maximum MTT ratios could be considered typical markers of neoplastic recurrence in irradiated cerebral tissue.

ER-beta expression in large bowel adenomas: implications in colon carcinogenesis.

BACKGROUND: A pivotal role of oestrogen receptor-beta has been suggested in colon carcinogenesis in humans. However, few data are available on oestrogen receptor-beta in colorectal pre-cancerous lesions. AIM: In the present study, we evaluated oestrogen receptor-beta expression and its possible correlation with proliferative activity and apoptosis in colorectal adenomas and normal colon tissue. PATIENTS/METHODS: Adenomatous tissue from 25 patients with colonic polyps, and normal tissue from 25 controls were used. Oestrogen receptor-beta expression, colonocyte proliferation (expressed as PCNA positivity) and apoptosis were evaluated. RESULTS: In adenomatous tissue, a significant reduction of oestrogen receptor-beta was observed compared to normal mucosa (10.1+/-5.5% vs. 44.2+/-13.7; p<0.03), while the expression of oestrogen receptor-alpha remained unvaried. Cell proliferative activity significantly increased in adenomatous tissue compared to normal mucosa (59.3+/-7.1 vs. 18.5+/-8.8; p<0.0001), doubling the PCNA/apoptosis ratio. An inverse correlation was found between oestrogen receptor-beta and PCNA expression in adenomas (r=-0.81), a datum confirmed by confocal microscopy evaluation. CONCLUSIONS: Our data demonstrate, for the first time, a significant reduction of oestrogen receptor-beta expression already in the pre-cancerous phase of colon carcinogenesis. This suggests a role of selective oestrogen receptor-beta agonists in the prevention of colorectal cancer.

Evidence of small-bowel involvement in hereditary hemorrhagic telangiectasia: a capsule-endoscopic study.

BACKGROUND AND STUDY AIMS: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder leading to telangiectases and arteriovenous malformations of the skin, mucosa, and viscera. Telangiectases in the upper gastrointestinal tract are known, but data regarding possible small-bowel involvement are scarce due to the technical difficulty of exploring the entire gastrointestinal tract. The aim of the present study was to use capsule endoscopy (CE) to determine the prevalence of small-bowel telangiectases in HHT patients. PATIENTS AND METHODS: From December 2001 to September 2002, 20 consecutive adult HHT patients at an interdepartmental HHT center were prospectively evaluated. All patients underwent esophagogastroduodenoscopy (EGD) followed by CE within 24 h. The telangiectases were scored according to commonly accepted criteria by two endoscopists and two observers of the video-capsule images, who were blinded to each other's findings. RESULTS: EGD revealed gastric telangiectases in 15 of the 20 patients (75 %), while CE demonstrated small-bowel involvement in 10 of 18 patients (56 %; images were not recorded for two patients due to battery failure). No preferential site for telangiectasia was found between the jejunum and the terminal ileum. All patients who were positive on CE were also found to have gastric involvement at EGD. Patients with small-bowel telangiectases were significantly older than those without (62.5 years vs. 45 years; P < 0.02). CONCLUSIONS: This study established a 56 % prevalence of small-bowel telangiectases in patients with HHT. This new endoscopic technique will probably change the etiological diagnosis of occult bleeding in HHT patients (which is too often attributed only to epistaxis) and may also be able to alter treatment strategies in HHT patients with gastrointestinal bleeding.