C. Bezzio

Long-term outcome of inflammatory bowel diseases with cytomegalovirus colitis: effect of antiviral treatment.

Objective The role of cytomegalovirus (CMV) reactivation in the outcome of inflammatory bowel diseases (IBDs) is unclear. Uncertainties remain on the treatment of CMV infection, especially in patients with a viral load just above the normal value in the blood or with very few positive cells in colonic biopsies. This retrospective cohort study reports the long-term outcome of 38 active IBD patients with CMV infection, 13 of whom received an antiviral treatment. Patients and methods Thirty patients with ulcerative colitis (UC) and eight patients with Crohn’s colitis with active colitis and CMV infection, diagnosed by detection of at least one CMV inclusion by histology and immunohistochemistry and/or with the CMV antigen test or the CMV DNA test, were studied. Their clinical history at 6 months and up to 1 year following hospital discharge was reviewed. Clinical remission at hospital discharge and recurrences requiring new treatments or colectomy were considered major outcomes of the study. The features of treated and untreated patients were compared using the Fisher exact test and the Student t-test. Results All patients showed rare CMV inclusions, and only three had positive blood CMV PCR. Thirteen patients received antiviral treatment, whereas 25 patients did not. No patient underwent colectomy during the hospitalization. The 12-month cumulative rate of clinical relapse requiring new treatment or colectomy was 23% in patients treated with antivirals and 50% in untreated patients (P=0.165). However, in patients with UC and in those with steroid-dependent/refractory disease, antiviral treatment was associated with a significantly higher clinical remission rate at 12 months (77.8 vs. 45%, P=0.049, and 77.8 vs. 19.4%, P=0.038, respectively). Conclusion In IBD patients with active CMV colitis, antiviral treatment seems to have a marginal impact in the short term, during the treatment of the acute phase, but it may have some beneficial effect in maintaining remission up to 1 year of follow-up in patients with UC and steroid-dependent/refractory disease.

Glucose intolerance and diabetes mellitus in ulcerative colitis: pathogenetic and therapeutic implications.

Diabetes mellitus is one of the most frequent co-morbidities of ulcerative colitis patients. The epidemiological association of these diseases suggested a genetic sharing and has challenged gene identification. Diabetes co-morbidity in ulcerative colitis has also relevant clinical and therapeutic implications, with potential clinical impact on the follow up and outcome of patients. These diseases share specific complications, such as neuropathy, hepatic steatosis, osteoporosis and venous thrombosis. It is still unknown whether the coexistence of these diseases may increase their occurrence. Diabetes and hyperglycaemia represent relevant risk factors for postoperative complications and pouch failure in ulcerative colitis. Medical treatment of ulcerative colitis in patients with diabetes mellitus may be particularly challenging. Corticosteroids are the treatment of choice of active ulcerative colitis. Their use may be associated with the onset of glucose intolerance and diabetes, with difficult control of glucose levels and with complications in diabetic patients. Epidemiologic and genetic evidences about diabetes co-morbidity in ulcerative colitis patients and shared complications and treatment of patients with these diseases have been discussed in the present review.

Ulcerative colitis: current pharmacotherapy and future directions

Introduction: Ulcerative colitis (UC) is a chronic relapsing disease, characterised by alternating of acute and remission phases. Although the aetiology is unknown, in recent years, there has progressively been greater knowledge of the various pathogenetic mechanisms underlying the disease itself. Thus, from therapy based on generically anti-inflammatory or immunosuppressive agents, treatment is gradually moving towards drugs that selectively block specific inflammatory mediators, such as TNF-α. Areas covered: This review provides the most significant data about the therapeutic role of different drugs currently available for the treatment of UC. In addition, the critical therapeutic areas on which research could focus in the near future are discussed. Expert opinion: UC is a disease affecting young patients, whose quality of life may be strongly compromised by the progression of disease. Over time, the disease may lead to an impairment of the normal anatomy and physiology of the colon, and the cumulative incidence of dysplasia and colorectal cancer increases with the time. Thus, the main aims of the near future should be both a better definition of patients at risk for a poor clinical course and progression of disease, and the development of a much more aggressive treatment for patients with a poor prognosis.

The impact of symptoms, irritable bowel syndrome pattern and diagnostic investigations on the diagnostic delay of Crohn's disease: A prospective study

BACKGROUND We investigated symptoms and tests performed prior to a formal diagnosis of Crohns disease and the reasons for diagnostic delay. METHODS Consecutive patients recently diagnosed with Crohns disease were enrolled between October 2012 and November 2013. Clinical data, symptoms including Rome III criteria at onset and at diagnosis, location and disease phenotype were recorded. Faecal calprotectin, radiological and endoscopic examinations performed prior to diagnosis were analysed. Diagnostic delay, stratified into tertiles and median time, was analysed using parametric and nonparametric tests. RESULTS 83 patients (49.4% males, median age 31 years) were enrolled. The median diagnostic delay was 8 (0-324) months. Twenty-six patients did not consult a general practitioner until diagnosis (31.3%), 18 presented to the emergency department (21.7%) and 8 directly to a gastroenterologist (9.6%). Diagnostic delay was not associated with specific symptoms. However, patients with bloating at presentation had a longer delay compared to those who did not (median, 6.1 vs. 16.8 months, respectively; p=0.016). Nineteen patients underwent incomplete ileocolonoscopies (22.9%) and 7 had no biopsies (8.4%), with a consequent diagnostic delay (median, 24 and 24 vs. 6 months, respectively; p=0.025 and p=0.008). CONCLUSION Diagnostic delay for Crohns disease is significantly associated with incomplete ileocolonoscopies, but not with symptoms, except bloating at presentation.

Gut and mesenteric lymph node involvement in pediatric patients infected with human immunodeficiency virus

Background The gastrointestinal tract is a primary target for human immunodeficiency virus (HIV). HIV infection causes a depletion of CD4+ T-lymphocytes in gut-associated lymphoid tissue and affects gastrointestinal mucosal integrity and permeability. The gastrointestinal tract has also been suggested as the main reservoir of HIV despite highly active antiretroviral therapy (HAART). We performed a prospective case-control study to assess gut involvement in HIV-infected patients, either naïve or on HAART, using noninvasive methods such as bowel ultrasound and fecal calprotectin. Methods Thirty HIV-infected children and youth underwent the following tests: CD4+ T-cell count and HIV viral load, fecal calprotectin, and bowel ultrasound, with the latter evaluating bowel wall thickness and mesenteric lymph nodes. Fecal calprotectin and bowel ultrasound were also assessed in 30 healthy controls matched for age and sex. Fecal calprotectin was measured using a quantitative immunochromatographic point-of-care test, and concentrations ranging from 0 to 200 μg/g were considered to be normal reference values in children. Results Fecal calprotectin was normal in 29 HIV-infected patients and was not significantly different from controls (mean values 63.8±42.5 μg/g and 68.3±40.5 μg/g, respectively; P=0.419), and did not correlate with HIV viral load, CD4+ T-cell absolute count and percentage, or HAART treatment. No significant changes were found on bowel ultrasound except for enlarged mesenteric lymph nodes, which were observed in seven HIV-infected patients (23.3%) and two controls (6.6%). This finding was significantly correlated with high HIV viral load (P=0.001) and low CD4+ T-cell percentage (P=0.004). Conclusion HIV-infected children did not have significant biochemical or ultrasonographic signs of bowel inflammation. A few patients showed enlarged mesenteric lymph nodes, which correlated with uncontrolled HIV infection.

P139 The learning curve of intestinal ultrasonography in assessing inflammatory bowel disease – preliminary results

Twenty-two patients (57.9%) had evidence of severe 25-(OH)D deficiency (<25 nmol/L); eleven patients (28.9%) showed serum levels consistent with deficiency (25 50 nmol/L); four patients (10.5%) had sub-optimal levels (50 75 nmol/L) and only one patient (2.6%) was found to have adequate levels. Conclusions: These results demonstrate that vitamin D deficiency is a significant finding amongst patients with CD on anti-TNF alpha therapy. Further work needs to be done to ascertain the effects of vitamin D deficiency on disease activity, but appropriate vitamin D screening and supplementation should be considered in patients with CD.

A safety evaluation of budesonide MMX for the treatment of ulcerative colitis

ABSTRACT Introduction: Budesonide belongs to low-bioavailability steroids class. A novel oral formulation of budesonide, which uses the Multi-Matrix System (MMX) for delivering drugs to the colon, is now available as a possible treatment of ulcerative colitis patients intolerant or not-responding to first-line therapy with 5-ASA. Areas covered: in this review we present information about the development and the use of budesonide MMX and we provide data about its mechanism of action as well as, pharmacodynamics and pharmacokynetics. Moreover, we present the available literature data about the efficacy and, mainly, the safety of budesonide-MMX. Expert opinion: budesonide-MMX is a new therapeutic option in mild-to-moderate UC patients. Its good safety profile in clinical trials undoubtedly represents a strength for a possible wide use in clinical practice, mainly if it will be confirmed by post-marketing data. Other indications, such as treatment of colonic Crohn’s disease, could theoretically be considered, if sustained by reliable scientific data.

New horizons in the imaging of perianal Crohn’s disease: transperineal ultrasonography

ABSTRACT Introduction: perianal disease, most commonly manifest as fistula or abscess formation, affects up to 40% of patients with crohn’s disease. perianal crohn’s disease is disabling, associated with poor outcomes, and represents a therapeutic challenge for physicians. correct diagnosis and classification of perianal disease is the first crucial step for appropriate multidisciplinary management. Areas covered: A literature search was performed of the PubMed database using the terms ‘transperineal ultrasonography’, ‘transperineal ultrasound’, ‘perianal disease’, ‘perianal fistula’, ‘perianal abscess’, ‘magnetic resonance’, ‘endoanal ultrasonography’, ‘endoscopic ultrasound’ in combination with ‘Crohn’s disease’. A comprehensive review of the relative advantages and disadvantages of the various methods of evaluation of perianal Crohn’s disease is provided. A particular focus is placed on transperineal ultrasonography, including historical and technical factors, advantages and limitations, and its current role in practice. An algorithm for integration of transperineal ultrasound into the management of perianal Crohn’s disease into clinical practice is proposed, along with future areas research. Expert commentary: Transperineal ultrasound is a simple, safe, cheap and reliable imaging technique for evaluation of perianal Crohn’s disease, which should be used more frequently in clinical practice.

Unrevealed Depression Involves Dysfunctional Coping Strategies in Crohn's Disease Patients in Clinical Remission

Background and Aims. This study investigated the proportion of CD patients in clinical remission with clinical depression, and coping strategies in those with severe depressive disorders. Materials and Methods. One hundred consecutive CD patients in clinical remission were screened for anxiety and depression by using Hospital Anxiety and Depression Scale and patients with depressive symptoms were further investigated by means of Cognitive Behavioural Assessment 2.0 and Beck Depression Inventory (BDI). Afterwards the coping strategies were assessed through the Brief-COPE questionnaire. Results. Twenty-one patients had anxious symptoms and 16 had depressive symptoms with or without anxiety. Seven of these patients (43.8%) showed significant depressive symptoms. Compared to patients without psychiatric disorders, these patients showed significant lower score in “positive reframing” (p: 0.017) and in “planning” (p: 0.046) and higher score in “use of instrumental social support” (p < 0.001), in “denial” scale (p: 0.001), and in “use of emotional social support” (p: 0.003). Conclusions. Depressed CD patients in clinical remission may have dysfunctional coping strategies, meaning that they may not be able to implement functional strategies to manage at best stress related with their disease.

The PROSIT Cohort of Infliximab Biosimilar in IBD: A Prolonged Follow-up on the Effectiveness and Safety Across Italy

BACKGROUND We report a prospective, nationwide cohort evaluating the safety and effectiveness of CT-P13. METHODS A structured database was used to record serious adverse events (SAEs), clinical remission/response, inflammatory biomarkers (CRP and calprotectin), and endoscopic findings. RESULTS Eight hundred ten patients with inflammatory bowel disease (IBD) (452 Crohns disease [CD]) were enrolled. Four hundred fifty-nine patients were naïve to anti-TNFα (group A), 196 had a previous exposure (group B), and the remaining 155 were switched to CT-P13 (group C). All patients were included in the safety evaluation with a mean follow-up of 345 ± 215 days and a total number of 6501 infusions. One hundred fifty-four SAEs were reported (19%), leading to cessation of the biosimilar in 103 subjects (12.7%). Infusion reactions were 71, leading to cessation of the biosimilar in 53 subjects (6.5%), being significantly more frequent in patients pre-exposed to anti-TNFα (P = 0.017). The efficacy of therapy was calculated in 754 IBD patients, with a mean follow-up of 329 ± 202 days. Forty-eight patients had a primary failure (6.4%), and 188 (25.6%) lost response during follow-up. Six hundred twenty-eight (364 CD) and 360 IBD patients (222 CD) completed the follow-up at 6 and 12 months, respectively. At 12 months, patients without loss of response were 71%, 64%. and 82% in groups A, B, and C, respectively (log rank P = 0.01). Clinical/endoscopic scores and inflammatory biomarkers dropped significantly in CD and UC patients (P = 0.01 and P < 0.0001) compared with baseline. CONCLUSIONS In this large prospective cohort, no further signals of difference in safety and effectiveness of CT-P13 in IBD has been observed.