Association of sleep quality and mucosal healing in patients with inflammatory bowel disease in clinical remission.

BACKGROUND: The interaction between sleep and the immune system has been increasingly studied over the last decades. The aim of this study was to investigate the association between sleep quality and mucosal healing in patients with inflammatory bowel disease (IBD) currently in clinical remission. METHODS: Ninety patients with IBD in clinical remission were studied: 54 (60%) with Crohn's disease and 36 (40%) with ulcerative colitis. All completed the Pittsburgh Sleep Quality Index, and mucosal healing was estimated with ileocolonoscopy. A subgroup analysis was also performed in order to investigate these associations in Crohn's disease and ulcerative colitis separately. RESULTS: Of the 90 patients, 45.56% had poor sleep quality. Patients without mucosal healing expressed higher absolute values of the Pittsburgh Sleep Quality Index (P<0.001), while absence of mucosal healing and poor sleep quality were statistically associated (P<0.05). Subgroup analysis showed that the same pattern was present in patients with Crohn's disease: patients without mucosal healing expressed higher absolute values of the Pittsburgh Sleep Quality Index (P<0.001) and the absence of mucosal healing was statistically associated with poor sleep quality (P<0.05). However, these associations were not observed in the subgroup of patients with ulcerative colitis (P>0.05). CONCLUSION: In patients with IBD in clinical remission, absence of mucosal healing seems to be associated with poor sleep quality, especially in patients with Crohn's disease.

Intestinal Bacteria Composition and Translocation of Bacteria in Inflammatory Bowel Disease.

BACKGROUND: Live commensal intestinal bacteria are present in the peripheral blood where they can induce inflammation. OBJECTIVE: To evaluate the intestinal bacteria composition and translocation of bacteria in IBD. METHODS: Both blood and tissue biopsy samples were collected from adult patients with active/inactive Crohn's disease (CD), active/inactive ulcerative colitis (UC) and healthy individuals. Most of the patients were newly diagnosed and none of them received antibiotics. Using a reverse transcription-quantitative real-time PCR (RT-qPCR) method, we determined the composition of microbiota. NOD2/CARD15 genotyping was also studied. RESULTS: Total bacterial DNA concentration was increased in tissue and blood samples of IBD patients compared to healthy controls. Furthermore, the active IBD cases had higher total bacterial DNA concentration levels compared to the inactive cases. Three species characterized dysbiosis in IBD, namely an increase of Bacteroides spp in active and inactive IBD samples, and a decrease in Clostridium leptum group (IV), and Faecalibacterium prausnitzi in both active and inactive IBD patients. No significant association between bacterial translocation and NOD2/CARD15 mutations was found. CONCLUSIONS: The composition of the microbiota in IBD patients differs from that of healthy controls. The high rate of bacterial DNA in the blood samples indicates translocation in inflammatory bowel disease.

Prevalence and Characteristics of Extra-intestinal Manifestations in a Large Cohort of Greek Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Extraintestinal manifestations [EIMs] are common in inflammatory bowel disease [IBD]. Data on epidemiology and risk factors of EIMs in IBD patients are limited. The aim of this study was to investigate the prevalence of EIMs in a large cohort of Greek IBD patients and identify risk factors for their development. METHODS: The study population consisted of IBD patients, who were followed in eight tertiary Greek hospitals. Demographic and clinical characteristics of patients were analysed. The diagnosis of EIMs was based on standard criteria and on specialist consultation. RESULTS: In total, 1860 IBD patients (1001 with Crohn's disease [CD], 859 with ulcerative colitis [UC]) were registered. Among them 615 [33.1%] exhibited at least one EIM; 238 patients [38.6%] developed an EIM before IBD diagnosis. An association between active IBD and presence of an EIM was established in 61.1% of the patients. Arthritic [peripheral arthritis], mucocutaneous [erythema nodosum], and ocular [episcleritis] were the most common manifestations. EIMs were more prevalent in females, patients with CD, smokers [for all p <0.0001], patients with extensive UC [p = 0.007], and patients with a previous appendectomy [p < 0.0001] or a major IBD-related surgery [p = 0.012]. CONCLUSIONS: About one-third of Greek IBD patients developed at least one EIM. Of those, more than one-third had their EIM diagnosed before IBD, and in about two-thirds it was related to disease activity. EIMs were more frequently present in females and patients with extensive UC in multivariate analysis.

Systemic lupus erythematosus in Crohn's disease: drug-induced or idiopathic?

Coexistence of Crohn's disease (CD) and idiopathic systemic lupus erythematosus (SLE) is very rare. On the other hand, drug-induced lupus erythematosus (DILE) due to anti-tumor necrosis factor (TNF) agents is a relatively more common entity. DILE due to anti-TNF agents and idiopathic SLE share common serologic and epidemiologic characteristics making the differentiation between those two entities difficult. We present a case of a 35-year-old woman with CD who developed SLE after treatment with adalimumab and denosumab and persisting symptoms eight months after discontinuation of those agents.

Sessile serrated adenomas versus conventional adenomas. Different polyps in different populations?

PURPOSE: The aim of this study was to determine risk factors for the development of sessile serrated adenomas (SSA/Ps) as well as to study differences between groups with SSA/Ps and conventional adenomas (tubular, tubulovillus and villus) in the general population. METHODS: One hundred patients with normal colonoscopies, 27 patients with 53 SSA/Ps and 69 patients with 156 conventional adenomas were studied, epidemiological data were collected and calculations of body mass index and waist-to-hip ratio were performed prior to endoscopy. A univariate and a multivariate logistic regression analysis were performed using Stata 9.0. RESULTS: SSA/Ps had a positive association with increasing age (p = 0.01), heavy smoking (≥20 packet years) (p = 0.001) and past history of polyps (p = 0.004) in comparison to normal population. SSA/Ps showed an inverse association with conventional adenomas for diabetes mellitus (p < 0.001) and arterial hypertension (p = 0.001). Meanwhile, female sex was positively associated with SSA/P development in comparison to conventional adenomas (p = 0.031). CONCLUSIONS: Heavy smoking as a significant risk factor for developing SSA/Ps was confirmed from this study. It also seemed that patients with diabetes mellitus and/or hypertension developed conventional adenomas more frequently than SSA/Ps; on the contrary, females were at higher risk of developing SSA/Ps than conventional adenomas.

Effect of infliximab on the healing of intestinal anastomosis. An experimental study in rats.

BACKGROUND AND AIM: Infliximab is effective in the induction and maintenance of remission in Crohn's disease. Whether, the perioperative administration of anti-TNF-a compromises intestinal healing leading to anastomotic failure and increased risk of postoperative complications, remains controversial. The aim of the study was to evaluate the effect of Infliximab on intestinal anastomosis healing. METHODS: Fifty six wistar rats were divided into 4 groups: (a) 20 rats were subjected to excision of part of the terminal ileum followed by anastomosis which was evaluated on the 3rd or 7th postoperative day; (b) 20 rats received Infliximab and thereafter, the same surgical protocol as group (a) was followed; (c) 8 rats received Infliximab and served as relative control group; and (d) 8 served as absolute control group. Bursting pressure was used for testing intestinal healing. Additionally, the anastomoses were examined macroscopically, histologically and immunohistochemically for TGFb1, MMP1, MMP2 and Collagen V. The results were confirmed by Western blot analysis. RESULTS: There were no significant differences in bursting pressures and septic intra-abdominal events among non-Infliximab (a) and Infliximab-treated (b) groups. Infliximab-treated (b) group showed mild to moderate inflammation, whereas the non-Infliximab (a) group exhibited severe inflammation. Expression of TGFb1, MMP2 and collagen V was significantly higher in the Infliximab-treated (b) group. CONCLUSION: Infliximab seems to influence intestinal healing in terms of less inflammatory activity and higher tissue remodeling activity.

Association study of genetic variants in miRNAs in patients with inflammatory bowel disease: preliminary results.

BACKGROUND: Aberrant expression and structural alteration of miRNAs are considered to participate in inflammation and cancer development. It has been suggested that common single-nucleotide polymorphisms (SNPs) in miRNAs are associated with susceptibility to several human diseases. METHODS: In the present preliminary study we evaluated the associations of two SNPs (rs2910164 and rs11614913 in miR-146a and miR-196a2, respectively) with the risk of inflammatory bowel disease (IBD) in a Greek population. RESULTS: The rs2910164 and rs11614913 SNPs were genotyped in 242 patients with Crohn's disease (CD), 210 patients with ulcerative colitis (UC) and 300 healthy individuals. No statistically significant differences were found in the genotype or allele distributions of the rs2910164 SNP among UC and control subjects. However, significant differences were found in the genotype or allele distributions of the rs2910164 polymorphism among CD and control subjects (P < 0.0001 and P < 0.0001, respectively). Concerning the rs11614913, no statistically significant differences were found in the genotype or allele distributions among CD and control patients, whereas TT genotype and T allele seem to have a protective role against UC (P = 0.017 and P = 0.007, respectively). The presence of rs2910164 and rs11614913 SNPs did not influence disease phenotype. CONCLUSIONS: Our results demonstrate that the rs2910164 polymorphism has a major role in genetic susceptibility to CD but not to UC, since the rs11614913 polymorphism had a protective role against UC, at least in the population studied here. Independent studies are needed to validate our findings in larger series and in patients of different ethnic origins.

Serrated polyps of right colon: guilty or innocent?

In recent years a lot of interest has been focused on a specific category of polyps, the so-called serrated polyps which until recently were categorized with the hyperplastic or mixed polyps and were thought to have no risk of malignant transformation. Recently though, the serrated pathway of carcinogenesis was discovered and destroyed this myth. It is believed that up to one third of all colorectal cancers arise through the serrated pathway; these cancers occur more often in the proximal colon and have specific molecular characteristics. Specific subtypes of serrated polyps (mainly the sessile serrated adenomas/polyps) are thought to be precursor lesions of these cancers. The prevention of these cancers is a challenge for gastroenterologists because their location and endoscopic characteristics renders them difficult to detect. Also, although there is a clear need for creating a specific post-polypectomy surveillance program for these lesions, to date there have been no guidelines for surveillance with a high level of evidence. In this article the main molecular, endoscopic, histological and epidemiologic characteristics of these lesions are presented, as well as recommendations for surveillance.

Cell turnover of serrated adenomas.

Serrated adenomas of the colon are characterized by epithelial neoplasia combining the architectural features of hyperplastic polyps and the cytological features of adenomas. Cell turnover, which is related to the malignant potential of these polyps, has not been thoroughly investigated. The aim of this study was to investigate epithelial cell proliferation, apoptosis, and oncoprotein expression in serrated adenomas. Twenty-five hyperplastic polyps, 25 serrated adenomas, and 25 tubulovillous adenomas resected from the colons of 75 patients were studied by immunohistochemical staining using monoclonal antibodies against MIB-1, Bcl-2, Bax, p53, and the TUNEL method for the detection of apoptosis. In serrated adenomas, the proliferation rate was significantly lower than in tubulovillous adenomas in both the lower and the upper parts of the crypts, and higher than that of hyperplastic polyps. Apoptosis was also significantly lower in serrated than in tubulovillous adenomas, but higher than in hyperplastic polyps. p53 oncoprotein expression was significantly greater in both serrated and tubulovillous adenomas than in hyperplastic polyps. bcl-2 protein expression was higher only in tubulovillous adenomas. Bax index was significantly different between tubullovillous and serrated adenomas, but the lowest values were observed in hyperplastic polyps. Serrated adenomas are highly proliferative polyps. They should be considered a biologically different entity from hyperplastic polyps. The intermediate features between serrated adenomas, hyperplastic polyps, and tubulovillous adenomas using the antibodies analysed in this study could have implications for the rate or the mechanism of development of malignancy in this type of polyp.