Current overview on hospitalization and surgery in inflammatory bowel disease

The incidence and prevalence of inflammatory bowel disease (IBD) are increasing globally, mainly in developing countries. Trends in rates of hospitalization and surgery over time can provide an overview about the progression of IBD worldwide and suggest the role of the introduction of new therapies in the modifying natural evolution of the disease, reducing structural damage, and consequently reducing hospitalizations and surgeries. This work demonstrated that all the advances observed, mainly in the last three decades, expressed through the reduction of hospitalization and surgery rates in most regions of the world, corroborate that the general management of patients with IBD has evolved, and postulate that drastic changes in pharmacotherapy could play a role

The Role of Innate Immunity Receptors in the Pathogenesis of Inflammatory Bowel Disease

Innate immunity constitutes the first line of defense, fundamental for the recognition and the initiation of an inflammatory response against microorganisms. The innate immune response relies on the sensing of microbial-associated molecular patterns through specialized structures such as toll-like receptors (TLRs) and the nucleotide oligomerization domain- (NOD-) like receptors (NLRs). In the gut, these tasks are performed by the epithelial barrier and the presence of adaptive and innate immune mechanisms. TLRs and NLRs are distributed throughout the gastrointestinal mucosa, being more expressed in the epithelium, and in lamina propria immune and nonimmune cells. These innate immunity receptors exhibit complementary biological functions, with evidence for pathways overlapping. However, as tolerance is the predominant physiological response in the gastrointestinal mucosa, it appears that the TLRs are relatively downregulated, while NLRs play a critical role in mucosal defense in the gut. Over the past two decades, genetic polymorphisms have been associated with several diseases including inflammatory bowel disease. Special emphasis has been given to the susceptibility to Crohn’s disease, in association with abnormalities in the NOD2 and in the NLRP3/inflammasome. Nevertheless, the mechanisms underlying innate immune receptors dysfunction that result in the persistent inflammation in inflammatory bowel disease remain to be clarified

Crohn's disease activity assessed by doppler sonography: the role of aortic flow parameters

OBJECTIVES: Intestinal neovascularization and abnormal abdominal arterial flow rates have been reported in Crohn's disease. The aim of this study was to evaluate Doppler sonography as a method for assessing Crohn's disease activity based on changes in splanchnic hemodynamics. METHODS: Forty-eight patients with Crohn's disease, 22 healthy volunteers and 12 patients with irritable bowel syndrome were evaluated by Doppler ultrasound for flow parameters of the aorta and superior mesenteric artery. This evaluation included the cross-sectional area, maximum flow volume, peak systolic velocity, end diastolic velocity, resistance and the pulsatility index. Disease activity was classified according to the Crohn's disease activity index. RESULTS: Most measurements in the aorta and superior mesenteric artery were significantly different between Crohn's disease patients and both control groups. Only the aortic maximum flow volume (CC = 0.37, p = 0.009) and aortic peak systolic velocity (CC = 0.30, p = 0.035) showed a significant positive correlation with the Crohn's disease activity index. The determination of cut-off points for the aortic maximum flow volume and peak systolic velocity measurements increased the sensitivity (80 and 75% for flow volume and velocity, respectively), specificity (57 and 75%), accuracy (67 and 75%) and positive (57 and 68%) and negative (80 and 81%) predictive values. These cut-off values permitted the correct classification of most of the patients with Crohn's disease with respect to disease activity. None of the superior mesenteric artery measurements were able to discriminate patients in relation to disease activity. CONCLUSION: The aortic maximum flow volume and peak systolic velocity levels estimated by Doppler sonography reflected disease activity in Crohn's disease. Doppler sonography of the aorta is therefore a novel noninvasive adjunct method that may be useful in the clinical follow-up of patients with Crohn's disease

FOCAL ENHANCED GASTRITIS AND MACROPHAGE MICROAGGREGATES IN THE GASTRIC MUCOSA: potential role in the differential diagnosis between Crohn’s disease and ulcerative colitis

Context and Objectives Focally enhanced gastritis and macrophage microaggregates are found in the upper gastrointestinal involvement of Crohn’s disease, and may reflect an underlying defective innate immunity. These features, however, are also described in patients with Helicobacter pylori infection. The role of these gastric abnormalities in the diagnosis of Crohn’s disease was assessed in a population with high prevalence of H. pylori infection. Methods Thirty-seven Crohn’s disease, 26 ulcerative colitis, and 30 control patients were included. The H. pylori status was evaluated by the rapid urease test and histology. The presence of focally enhanced gastritis and macrophage microaggregates was recorded. Results Focally enhanced gastritis was present in 24% of Crohn’s disease patients, 4% of ulcerative colitis patients and 11.5% of controls, presenting an overall sensitivity and specificity for Crohn’s disease of 24% and 88%, respectively. Macrophage microaggregates were found in all groups, but were only detected in ulcerative colitis and controls in association with H. pylori infection, with an overall sensitivity and specificity for Crohn’s disease of 61% and 69%, respectively. In the absence of H. pylori infection, focally enhanced gastritis and macrophage microaggregates were significantly associated with Crohn’s disease (P<0.02 and P = 0.001 respectively). Conclusions Focally gastritis and macrophage microaggregates are suggestive of Crohn’s disease only in H. pylori-negative specimens. HEADINGS - Crohn’s disease. Ulcerative colitis. Gastritis. Macrophages. Helicobacter pylori

Immunohistochemical analysis of retinoblastoma and β-catenin as an assistant tool in the differential diagnosis between Crohn's disease and ulcerative colitis.

In about 10-15% of patients with inflammatory bowel diseases (IBD) there is no clear definitive differential diagnosis between Crohn's disease (CD) and ulcerative colitis (UC) and the disease is classified as indeterminate colitis. Since pharmacological and surgical treatments differ in CD and UC, establishing a correct diagnosis is critical. The aim of this work was to access the expression profile of proteins involved in colonic inflammation and cancer in samples from CD and UC. For that, colon samples from 24 CD, 21 UC and 10 control patients were processed for immunohistochemistry using anti-phosphorylated RB at Ser(807/811) and anti-β-catenin. Crypts were blinded, analyzed and counted for phosphorylated RB-positive (phospho-RB) cells or scored for positive β-catenin staining. Western blot was used for confirming immuhistochemical results: RB phosphorylation was significantly greater in colon samples from patients with CD compared with UC (p<0.005). In contrast, the expression of β-catenin was significantly increased in UC compared with CD (p<0.005) samples. Phospho-RB and β-catenin are negatively correlated (CC: -0.573; p = 0.001). A positive phospho-RB test yielded high levels of sensitivity, specificity, negative and positive predictive values, and accuracy for the diagnosis of CD against UC. This work indicates that RB phosphorylation and β-catenin nuclear translocation are differently expressed in CD and UC, and provide novel insights into the pathogenic mechanisms of IBD. In particular, rates of phospho-RB-positive cells in mucosal samples emerge as a promising tool for the differential diagnosis of patients with IBD

hTERT gene methylation in circulating DNA, tumor, and surrounding tissue in breast cancer: a prospective study

ABSTRACT BACKGROUND: The human telomerase reverse transcriptase (hTERT) enzyme, encoded by the hTERT gene, synthesizes protective telomeric sequences on chromosomes and plays a fundamental role in cancer formation. Methylation of the hTERT gene has an upregulatory effect, increasing hTERT enzyme synthesis and allowing continuous tumor cell division. OBJECTIVE: In a group of patients with breast cancer, we aimed to analyze the methylation status of hTERT in the tumor, surrounding tissue, and circulating free deoxyribonucleic acid (cfDNA) of blood collected on the day of mastectomy and then approximately one year later. DESIGN AND SETTING: A prospective study was conducted at a university hospital in Rio de Janeiro, Brazil. METHODS: Samples were collected from 15 women with breast cancer on the day of mastectomy and approximately one year postoperatively. cfDNA was analyzed by sodium bisulfite conversion, followed by polymerase chain reaction, electrophoresis, and silver nitrate staining. RESULTS: Methylation of hTERT was detected in the tumors and surrounding tissues of all 15 patients. Five patients displayed hTERT methylation in the cfDNA from the blood of the first collection. Of the ten patients who returned for the second collection, three showed methylation. Two patients with methylation in the first collection did not display methylation in the second collection. One patient with no methylation in the first collection displayed methylation in the second collection, and one patient had a diminished level of methylation in the second collection. CONCLUSION: Only one-third of patients displayed methylation in their cfDNA, which may be related to the success of chemotherapy