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அழற்சி குடல் நோய்கள் மற்றும் கோளாறுகளின் இதழ்

ஐ.எஸ்.எஸ்.என்: 2476-1958

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தொகுதி 1, பிரச்சினை 1 (2016)

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New Onset Ulcerative Colitis: Case Analysis and Correlations to Pathogenesis

Jay Pravda

New onset ulcerative colitis appearing with or soon after an associated comorbidity represents a unique opportunity to analyze and identify the events that may have triggered the colonic inflammation. The characteristic colonic mucosal inflammatory manifestations observed in ulcerative colitis lends itself to a common pathway analysis within the pathophysiology of associated comorbid triggering conditions. Under these unique circumstances the pathophysiology of one disease becomes the pathogenesis of another, in this case ulcerative colitis. Since the pathophysiology of the triggering comorbidity is usually known, all that remains is to identify a common pathophysiological event in each of the triggering comorbidities that can serve as a common pathway in the pathogenesis of ulcerative colitis (triggered condition). For this common pathway analysis six case reports have been chosen from the literature in which new onset ulcerative colitis is associated with a comorbid condition that is presumed to have triggered the inflammatory bowel disease, with the aim of identifying the common pathway leading to ulcerative colitis. The results suggest a pathogenesis in which an oxidative stress pathway culminates in the production of excess hydrogen peroxide within colonic epithelial cells. Hydrogen peroxide is a toxic by-product of normal metabolism that can initiate mucosal inflammation after diffusing out of colonic epithelial cells.

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“Barriers Breached”: Pancreaticorenal Fistula Complicating Acute Pancreatitis–A Case Report

Udit Chauhan

Pancreatitis could be acute or chronic with both the forms causing spectrum of complications. Walled off necrosis or pseudocysts complicating pancreatitis can form at variable number of locations. Pseudocyst occurring at perinephric space is a rare complication. It can cause variety of symptoms like hematuria and renal compression. Authors present two such cases of pancreaticorenal fistula complicating acute pancreatitis which were successfully treated with percutaneous drainage.

ஆய்வுக் கட்டுரை

Initial Site of Crohn’s Disease is not an Independent Predictor of Outcome of Short Bowel Syndrome

Wheeler MJ, Langenfeld SJ, Lyden E, Weseman RA, Rochling FA and Thompson JS

Objective: Patients with Crohn's disease (CD) are at risk for Short Bowel Syndrome (SBS). Our aim was to determine the effect of initial site of disease on outcome in patients with CD developing SBS. Methods: We reviewed the outcome of 87 adult CD patients with SBS. Thirty-eight (44%) had initial ileocolonic disease, 27(31%) had colonic disease and 22(25%) had small intestinal disease. Results: Compared to patients with small intestinal and ileocolonic disease, patients with initial colonic disease were more likely to have a total colectomy (85% vs 32% and 37%, p<.05) and have an ostomy (89% vs 37% and 34%, p<.05). Intestinal remnant length was similar. Intestinal remnant length was the only predictor of need for longterm(> 1year) Parenteral Nutrition (PN) (p<0.0001). CD site at presentation was not significant on multivariate analysis (p=0.40). Conclusion: Patients with CD with colon as the initial site of disease who develop SBS have different anatomic characteristics. However, initial site of disease is not an independent predictor of need for long-term PN.

கட்டுரையை பரிசீலி

Vascular Complications in Inflammatory Bowel Disease: An ObservationalStudy

Sara Campos, Francisco Portela and Carlos Sofia

Introduction: Increasing evidence has raised an alert about the potential risk of vascular complications in Inflammatory Bowel Disease (IBD). Estimating the magnitude of this risk is imperative to better address IBD patients. The aim of this study was to determine the venous (VTE) and Arterial Thromboembolic Events rates (ATE), as well as the Cardiovascular Events (CVE) and related mortality in IBD inpatients.
Methods: Retrospective study including all inpatients from a tertiary hospital with IBD from 1st August 2006 to 31st May 2013 with an episode of VTE/ATE/CVE. The population was characterized using the following variables: IBD (age of diagnosis, type, location/extension/behavior using Montreal classification, activity, medication), vascular complication (diagnosis age, type, location), classical VTE and ATE/CVE risk factors, pharmacological venous thromboembolism prophylaxis and outcome (recurrence, 30-day mortality).
Results: We recorded 774 admissions of IBD patients, 28 (3.6%) with thromboembolic episode: 57% male gender; average age 58 ± 17 years (13.8%

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The Risk of Hepatosplenic T-Cell Lymphoma (HSTCL) in Women with Inflammatory Bowel Disease (IBD) on Thiopurines

Shirley Cohen-Mekelburg, Yecheskel Schneider, Marco Pizzi, Amy Chadburn, Susan Mathew, Ellen Scherl and Adam Steinlauf

Hepatosplenic T-cell Lymphoma (HSTCL) is a rare and often fatal malignancy classically thought to affect males less than 35 years of age with Inflammatory Bowel Disease (IBD) on thiopurines. Even though HSTCL is thought to affect predominantly young males with IBD, it can occur in female patients as well. We report a case of HSTCL in a young female patient with ulcerative colitis (UC), the 6th female case of IBD-associated HSTCL reported in the literature. Although the risk of developing HSTCL may be lower in women, it remains a substantial concern given the aggressive nature of this disease.

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Capsule Endoscopy for Differentiating Early Crohn's Disease from Behçet's Disease

Miwa Satake, Hirotake Sakuraba, Hiroto Hiraga, Norihiro Hanabata, Noriko Hiraga, Keisuke Hasui, Shinji Ota, Yui Akemoto, Tatsuya Mikami, Yoh Ishiguro and Shinsaku Fukuda

Objective: Crohn's disease (CD) and Behçet's disease (BD) are two major causes of inflammatory lesions in the small bowel. For detecting such lesions, the most sensitive exam is small-bowel capsule endoscopy (CE), an imaging modality suitable for evaluating lesions of the small intestine, with a relatively low rate of capsule retention. However, few reports have employed CE to compare the small-bowel inflammation in early CD with that in early BD. Thus, the aim of our study was to obtain a systematic characterization of small-bowel lesions in early CD and BD by using CE.
Methods: This retrospective single-center study included 22 patients with early CD and 16 patients with early BD. The patients underwent small-bowel CE for detection and characterization of small-bowel lesions. After reviewing the CE findings in each patient, we assessed the small-bowel mucosal inflammation using the Lewis score, an inflammatory biomarker (C-reactive protein), and the disease activity index. The CE findings (number, distribution, and shape of lesions), Lewis score, disease activity index, and C-reactive protein levels were compared between the groups of CD and BD patients.
Results: Small-bowel lesions were observed in 90.9% of CD patients, and in 68.7% of BD patients. Regarding distribution, CD patients exhibited multiple concentrated ulcers, which were more severe distally, while BD patients mostly exhibited solitary ulcers. Regarding shape, linear and longitudinal ulcers were observed, respectively, in 68.2% and 50% of CD patients; however, no such ulcers were observed in BD patients. C-reactive protein levels and disease activity indices were poorly correlated with Lewis score for both diseases. Capsule retention during CE did not occur in any patient included in this study.
Conclusion: CE is a valuable tool to assess the mucosal inflammation of the small bowel in early CD and BD. Greater mucosal inflammation in the distal small bowel, and presence of linear and longitudinal ulcers may be the key findings for the differential diagnosis of small-bowel inflammation between early CD and BD

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Genetic and Demographic Correlates of Quality of Life after Ileal Pouch Anal Anastomosis for Ulcerative Colitis

Tara M Connelly, Bailey Sanders, Arthur S Berg, Emmanuelle Williams, Leonard Harris III, Andrew Tinsley, Walter A Koltun

Objective: Patient satisfaction after ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) is difficult to predict preoperatively and has never been investigated from a genetic perspective. Methods: Modified IBD quality of life (QOL) questionnaires were mailed to all UC-IPAA patients in our IBD Biobank. Genotyping was performed using a custom microarray containing 325 IBD-associated single nucleotide polymorphisms (SNPs). Fisher's exact and Mann-Whitney tests and logistic regression with the Bonferroni correction were used for analysis. Results: Response rate was 69% (142 of 206 patients, mean pouch duration=10.1 ± 0.5years). Patients diagnosed at a younger age and with shorter time to colectomy reported poorer emotional wellbeing scores. Readmission post-colectomy was significantly associated with poor overall and emotional scores. On multivariate analysis, female gender and readmission were predictors of poor overall QOL. Poorer emotional wellbeing and systemic symptom scores were found in patients who had undergone colectomy urgently. Smoking history correlated with poor bowel and social scores. SNP rs2279627 associated with the immunoregulatory TNFSF14 gene and two POU5F1/OCT4 gene related SNPs, rs7837328 and rs7014346, were significantly associated with poorer emotional wellbeing scores. Rs2279627 was also significantly associated with poorer scores in the overall and bowel symptom categories. Conclusions: 1) Female gender, short

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Educational Needs of Patients with Inflammatory Bowel Disease (IBD) and Non-Adherence to Medical Therapy-A Qualitative Study

Wheat CL, Megan Maass, Beth Devine, Timothy Thornton, David Grembowski and Cynthia W Ko

Objective: Patients with IBD are at risk for serious complications when their disease is poorly managed. Patient non-adherence to medical therapy contributes to suboptimal outcomes, but may be modified through improved education. The primary aim of this study is to identify educational needs, and barriers and factors associated with non-adherence among inflammatory bowel disease (IBD) patients.
Methods: Eighteen IBD patients and ten IBD providers were recruited. Semi-structured interviews were conducted and a qualitative framework approach used to identify patient educational needs, barriers to obtaining information, and factors associated with non-adherence with medical therapy.
Results: Prevention of IBD symptoms and factors contributing to development of IBD were the most frequently identified patient educational needs. Both providers and patients identified diet and nutrition, as well as access to general information about IBD, as important areas of education. Common barriers to obtaining or conveying information for patients and providers included: information oversaturation, ineffective provider communication skills, and lack of provider time. Factors that impact patient comprehension and decision making were also identified. Providers frequently believed that patient non-adherence is associated with lack of current symptoms or denial of their chronic condition.
Conclusion: Our findings highlight several deficits in knowledge in IBD patients. We also identify factors associated with IBD patient comprehension, decision making, and non-adherence to therapy. These results can be used to develop targeted educational resources to improve adherence among IBD patients. We propose that patient self-management programs are potentially effective educational interventions that warrant further study in IBD.

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Alpha-Defens in 5 Expression is Regulated by microRNAs in the Caco-2 Intestinal Epithelial Cell Line

Donald R B Miles

Abstract Background: In inflammatory bowel disease (IBD), an inappropriate immune response leads to chronic mucosal inflammation. This response may be partly due to dysregulation of defensins, which are endogenously produced antimicrobial peptides. This study determined whether microRNAs (miRNAs) regulate α-defensin 5 (DEFA5), which could further implicate both in IBD pathogenesis. Methods: Induction of DEFA5 mRNA and protein expression was determined in Caco-2 cells. An in silico analysis identified putative miRNA binding sites of DEFA5. Expression of these miRNAs was assessed in Caco-2 cells. Regulation of DEFA5 expression by these miRNAs was measured by luciferase assays. Caco-2 cells were transfected with miR-124 and miR-924 mimics, and DEFA5 mRNA and protein expression was measured. Results: DEFA5 mRNA and protein expression was inducible in Caco-2 cells. Fifteen putative miRNA binding sites were found in DEFA5. The expression of miR-124 and miR-924 decreased following induction. Transfection of a luciferase construct containing the DEFA5 miRNA binding sites resulted in a decrease in luciferase activity compared to transfection of the empty vector. Transfection of a reporter construct containing mismatched miRNA binding sites resulted in restoration of luciferase activities. Transfection of miRNA mimics decreased DEFA5 mRNA expression and protein expression. Conclusions: miR-124 and miR-924 negatively regulate DEFA5 mRNA and protein expression. These data implicate miRNAs in intestinal innate immune regulation and IBD pathogenesis.

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Higher Trough Concentrations of Infliximab are Associated with Clinical Remission and Mucosal Healing in Patients with Inflammatory Bowel Disease

Parra RS, Marley Ribeiro Feitosa, José Joaquim Ribeiro da Rocha, and Omar Féres

Objective: Few studies have correlated the infliximab (IFX) trough concentration, clinical remission (CM) and mucosal healing (MH). The purpose of the study was to determine if higher IFX trough levels are associated with MH and CR, in a group of Brazilian inflammatory bowel disease patients. Methods: Cross-sectional study of 51 IBD patients in IFX maintenance therapy, at a medical center, in Brazil. IFX serum levels were obtained from blood samples collected immediately before drug infusion. The IFX trough levels were correlated with clinical and endoscopic scores and a univariate analysis was conducted to identify factors associated with CR and MH. Results: IFX trough concentration ≥ 2 μg/mL was associated with higher CR (84.2% vs. 28.1%; P<0.001) and MH (83.3% vs. 25.0%; P=0.001). Trough levels of 2.0 μg/mL were 89% specific for CR (sensibility=66%; P<0.001) and 89% specific for MH (sensibility =64%; P<0.001). On univariate analysis, IFX trough concentration was the only variable associated with CR and MH. Conclusion: The study found a significant association between IFX trough level ≥ 2 μg/mL, CR and MH. Therapeutic drug monitoring is an important tool in IBD patients and should routinely be performed to optimize treatment.

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Order of Presentation of Pediatric Siblings Inflammatory Bowel Disease

Richard L Mones

Aim: To determine the birth order of presentation of pediatric siblings with Inflammatory Bowel Disease (IBD).
Methods: We selected all siblings from our data base of pediatric patients with IBD and determined which sibling presented with IBD first and then second.
Results: In 16 pairs of siblings, the second born sib presented first in 69% of the time.
Conclusion: Antibiotic exposure, or other environmental factor(s) may be responsible for the distribution of presentation we found. 

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A Successful Treatment of Anterior nodular Scleritis with Topical Corticosteroids in a patient with Crohn's Colitis

Galanopoulos M, Nikolaidou E, Sarafis A, Liatsos C and Kalafatis E

Scleritis is a chronic, painful, potentially blinding disorder that may also involve the cornea, the adjacent episclera and the unveil tract. It is often associated with ocular complications (corneal changes, glaucoma, cataracts) and in up to 50% of patients it is accompanied by an underlying systemic illness such as rheumatoid arthritis , Wegener’s granulomatosis or inflammatory bowel diseases (IBDs). It is considered to be a relatively rare extra-intestinal ocular manifestation of IBDs (about 2%). This case report represents an anterior nodular scleritis in a patient with Crohn’s colitis who had been primarily treated with topical ophthalmic corticosteroids, and was on infliximab therapy for the underlying disease for three years. Treating a mild form of scleritis with topical corticosteroids could be a reasonable therapeutic option for patients receiving an anti-TNF agent for subjacent inflammatory bowel disease, in order to avoid further immunosuppression with systemic anti-inflammatory drugs.

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