Mircea Diculescu

Efficacy, safety and tolerability of vidofludimus in patients with inflammatory bowel disease: the Entrance study.

BACKGROUND Vidofludimus (SC12267) is a novel oral immunomodulator inhibiting dihydroorotate dehydrogenase (DHODH) and the expression of proinflammatory cytokines including interleukin-17 (IL17A and IL17F) and interferon-gamma. The objective of the study was to explore the efficacy, safety and tolerability of vidofludimus in steroid-dependent inflammatory bowel disease (IBD). METHODS The open label uncontrolled ENTRANCE study (ClinicalTrials.gov NCT00820365) has been conducted at 13 study centers in Germany, Bulgaria and Romania. Thirty-four steroid-dependent patients with a confirmed diagnosis of Crohns disease (CD) or ulcerative colitis (UC) were treated with a once daily 35mg oral dose of vidofludimus over 12weeks. Steroids were tapered during the first 8weeks followed by a steroid-free treatment period of 4weeks. Complete response was defined as steroid-free clinical remission at week 12; partial response was defined as being in remission at steroid dose equal or lower than the individual patients threshold dose for relapse. RESULTS Of the thirty-four patients enrolled in this trial 26 were evaluable for primary efficacy assessment. After completion of the 12weeks treatment phase 8 out of 14 (57.1%) patients with CD and 6 out of 12 (50.0%) patients with UC were in steroid-free remission (complete responders). Another 4 (28.6%) patients in CD and 5 (41.7%) patients in UC were partial responders. Vidofludimus was well tolerated, no drug-related serious adverse events were observed. CONCLUSIONS This trial provides first evidence of clinical efficacy of vidofludimus in IBD. Although the safety and tolerability profile seems favorable, long-term controlled studies are needed to further investigate its potential as novel IBD therapy.

Diagnostic Delay in Romanian Patients with Inflammatory Bowel Disease: Risk Factors and Impact on the Disease Course and Need for Surgery

BACKGROUND The epidemiology of inflammatory bowel disease [IBD] in Eastern Europe is poorly understood, particularly with regard to diagnostic delay. Here we investigated the factors leading to delayed diagnosis and the effect of the delay on several disease progression and outcome measures. METHODS A total of 1196 IBD cases [682 ulcerative colitis [UC], 478 Crohns disease [CD], 36 indeterminate colitis] from the Romanian national registry IBDPROSPECT were reviewed. Standard clinical and demographic factors were evaluated as predictors of a long diagnostic delay in both CD and UC. Diagnostic delay was subsequently evaluated as a potential risk factor for bowel stenoses, bowel fistulas, perianal fistulas, perianal surgery, and intestinal surgery in CD patients. RESULTS The median diagnostic delay was significantly longer in CD [5 months] than in UC [1 month] patients [p < 0.001]. Compared with 5 months for UC patients, 75% of CD patients were diagnosed within 18 months of symptom onset. In CD patients, extra-ileal location was a protective factor (odds ratio [OR], 0.5; p = 0.03), whereas being an active smoker [OR, 2.09; p = 0.01] and symptom onset during summer [OR, 3.35; p < 0.001] were independent risk factors for a long diagnostic delay [> 18 months]. In UC patients, an age > 40 years was a protective factor [OR, 0.68; p = 0.04] for a long delay. Regarding outcomes, a long diagnostic delay in CD patients positively correlated with bowel stenoses [OR, 3.38; p < 0.01] and any IBD-related surgery [OR, 1.95; p = 0.03] and had a positive trend for intestinal fistulas [OR, 2.64; p = 0.08] and perianal fistulas [OR, 2.9; p = 0.07]. Disease duration since diagnosis positively correlated with bowel stenoses [OR, 1.04; p = 0.04], any IBD-related surgery [OR, 1.04; p = 0.02], and intestinal surgery [OR, 1.07; p < 0.01]. CONCLUSIONS A long diagnostic delay in IBD correlates with an increased frequency of bowel stenoses and need for IBD-related surgery.

Inflammatory gene expression profiles in Crohn's disease and ulcerative colitis: A comparative analysis using a reverse transcriptase multiplex ligation-dependent probe amplification protocol

BACKGROUND AND AIMS Cytokines and their receptors play a critical role in the pathogenesis of the inflammatory bowel disease (IBD). The aim of this study was to investigate the expression profiles of inflammatory genes in inflamed and non-inflamed colonic tissue samples in patients with Crohns disease (CD) and ulcerative colitis (UC), and to identify molecular signatures for different IBD phenotypes. METHODS Seventy-one patients diagnosed with IBD (38 CD, 33 UC) and 15 non-IBD controls have been included in the study. For each patient, biopsy samples were obtained during colonoscopy from inflamed (L) and healthy (N) mucosa. We investigated by commercially available reverse-transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) kit the mRNA expression of a set of 40 genes involved in inflammation: cytokines, chemokines, receptors, signal transduction molecules and transcription factors. RESULTS In L biopsies from patients with CD, higher expression levels were found for IL-4 (p=0.009) and IL-12p35 (p=0.0005), whereas in L biopsy samples from patients with UC higher expression levels were found for IL-8 (p=0.03), chemokines SCYA3 (p=0.05), SCYA4 (p=0.01) and glutathione S-transferase P1 (p=0.01). In N biopsies of patients with CD higher expression levels were found for IL-1R (p=0.01) and IL-12p35 (p=0.007), whereas in N biopsies of patients with UC higher expression levels were found for IL-15 (p=0.009) and SCYA8 (p=0.001). The logistic regression analysis has indicated that low expression levels of IL-2 and IL-10, together with higher ASCA IgG titers were independently associated with penetrating/stricturing CD. CONCLUSIONS RT-MLPA is a sensitive and effective method for the evaluation of the profiles of inflammatory genes in IBD, with potential future applications for diagnosis, phenotypic stratification and targeted therapy.

Prevalence and impact on survival of hepatopulmonary syndrome and cirrhotic cardiomyopathy in a cohort of cirrhotic patients

Extrahepatic complications of cirrhosis increase the risk for decompensation of the liver disease and death. Previous studies show common pathogenetic mechanisms involved in the development of hepatopulmonary syndrome and cirrhotic cardiomyopathy. We aimed to assess the link between these entities and their effect on disease‐related patient morbidity and mortality.

Real-world efficacy and safety of ombitasvir, paritaprevir/r+dasabuvir+ribavirin in genotype 1b patients with hepatitis C virus cirrhosis†

Direct antiviral agents (DAA) showed very good results in terms of efficacy and safety in clinical trials, but real‐life data are still needed in order to confirm this profile.

Ectopic pancreas mimicking gastrointestinal stromal tumor in the stomach fundus

Ectopic or heterotopic pancreas refers to healthy pancreatic tissue that lacks anatomical, vascular or neural communication with the normal pancreas. However, heterotopic pancreas is seldom considered as a diagnostic hypothesis when symptomatic or when located outside of the gastric antral wall [1]. This case report describes the clinical and paraclinical features of pancreatic heterotopia in the gastric fundus in a previously healthy 25-year-old woman. Initially, a gastrointestinal stromal tumor (GIST) was highly suspected because of its endoscopic (location and shape; ▶Video1), endoscopic ultrasound (emerging layer; ▶Fig. 1, ▶Fig. 2), and computed tomography characteristics; however, the histopathological evaluation revealed pancreatic heterotopia (▶Fig. 3). Although the patient was asymptomatic, we opted for surgical treatment because of the large size of the lesion, the atypical location in a highly vascularized part of the stomach, and the patient’s young age. On postsurgical follow-up, only a small granuloma was found on the suture site, even though the surgery was not curative (R1 with remaining pancreatic tissue on one margin of the resection specimen) (▶Fig. 4). We emphasize the unusual location of the pancreatic heterotopia (gastric fundus – despite up to 95% of cases being found in the antral location), and the layer from which the tissue developed (muscularis propria – which is seen in only 17% of cases) [2]. Moreover, we emphasize the difficulty in making an accurate diagnosis, which can only be obtained after surgery, and the need for regular postoperative follow-up to assess for remaining pancreatic rests, as some studies have shown up to 12.7% malignant transformation in pancreatic rests [3]. Despite the fact that ectopic pancreas is a rare condition, one must consider the differential diagnosis of extramucosal gastric lesions. Even though endoscopic Video 1 Endoscopic appearence of a submucosal lesion, with central ulceration, in the gastric fundus. Narrow-band imagining revealed regular microvascular and surface patterns, except for the central zone, which had irregular surface and vascular patterns.

Mortality in Digestive Cancers, 2012: International Data and Data from Romania.

We aimed to compare the difference in case fatality rate between more developed and very high Human Development Index (HDI) regions, less developed and low HDI regions, and Romania. The incidence and mortality rates for digestive cancers were obtained from the IARC/WHO 2012 database. World mean mortality-to-incidence ratios registered the highest values in pancreatic cancer (0.97/0.94), and liver cancer (0.93/0.96) in males/females, respectively. The lowest values were recorded in colorectal cancer (0.48 in both sexes). Mortality-to-incidence ratios were generally higher in less developed areas, low HDI populations, and in Romania. The difference in case fatality rate between different areas showed higher variations for colorectal, gastric and gallbladder cancers, and smaller variations for esophageal, liver, and pancreatic cancers. In summary, mortality-to-incidence ratios of digestive cancers were high in 2012; higher values were registered in less developed and low HDI regions, and in Romania. Mortality-to-incidence ratios were similar in both sexes, even though the incidence was generally higher in men. Digestive cancer mortality variation suggests the necessity of finding better strategies for prevention, early diagnosis and treatment of digestive cancers.

P626 Extraintestinal manifestations in Romanian IBD patients – evaluation of a cohort of over 1000 patients

Results: Two hundred seventy-five patients (143 males and 132 females) were colliged. Mean age was 31.8 years old [8 65]. They were followed during a mean period of 23.3 months. Familial form (FF) of CD was diagnosed in 32 patients (11.6%). Age at onset of CD, site and phenotype of CD were similar in FF and sporadic forms (SF) (respectively p = 0.2, p = 0.6 and p = 0.9). Upper gastrointestinal tract involvement, anoperineal lesions and complications such as abcess and severe acute colitis were as common in FF as in SF of CD. Extraintestinal manifestations were significantly more frequent in FF than SF (45.1% versus 21.5%, p = 0.005). Corticosteroids were more commonly prescribed in FF than in SF (75% versus 55%, p = 0.026). Overall, patients with FF receive more immunosuppressive therapy than patients with SF (65.6% versus 48.5%, p = 0.05) mainly methotrexate (12.5% versus 1.6%; p = 0.008). There was no difference between FF and SF of CD with regard of Biotherapy with anti-TNF agents (15% versus 8%; p = 0.1) and surgery (8% versus 35%, p = 0.2). Conclusions: Despite comparable clinical characteristics of both groups, extraintestinal manifestations may result in more common use of corticosteroids and immunosuppressive therapy in FF than in SF of CD.

P400 Opportunistic infections in anti-TNF treated IBD patients: analysis from three tertiary centers in Romania

P399 Oral butyrate plus inulin improve serum metabolomic profile and gut microbiota composition in ulcerative colitis and celiac disease S. Sitkin1,2 *, E. Tkachenko2, T. Vakhitov1, L. Oreshko2, T. Zhigalova2. 1State Research Institute of Highly Pure Biopreparations, Dept. of Applied Microbiology, St. Petersburg, Russian Federation, 2North-Western State Medical University named after I.I. Mechnikov, Dept. of Propaedeutics of Internal Diseases, St. Petersburg, Russian Federation

P587 The prevalence of anaemia and iron deficiency in IBD inpatients and outpatients in Romania – an interim analysis on the first 120 patients

Conclusions: Accurate diagnosis of IBD is made by experienced physicians. The patients having suspicious symptoms must be sent to most experienced physicians without delay. The time from onset of symptoms to diagnosis was median 8.3 months in CD, 4.5 months in UC in IBSEN study. Our study results were generally compatiple with the literature. Early diagnosis can decrease the risk of progression to complicated disease that is required more effective and expensive drugs.