Venigalla Pratap Mouli

Review article: vitamin D and inflammatory bowel diseases

Vitamin D is traditionally associated with bone metabolism. The immunological effects of vitamin D have increasingly come into focus.

Efficacy of Conservative Treatment, Without Necrosectomy, for Infected Pancreatic Necrosis: A Systematic Review and Meta-analysis

BACKGROUND & AIMS Conservative treatment (intensive care, a combination of antimicrobial agents, and nutritional support, with or without drainage of the infected fluid) has recently been shown to be effective for patients with infected pancreatic necrosis (IPN), but the data from individual studies are not robust enough to recommend it as the standard of care. We performed a systematic review and meta-analysis of studies related to primary conservative management for IPN. METHODS We performed a literature search of MEDLINE/PubMed from January 1990 to March 2012 for studies of a priori protocols for primary conservative treatment, without necrosectomy, for consecutive patients with IPN. We analyzed data from 8 studies, comprising 324 patients with IPN who received primary conservative management. We then analyzed an additional 4 studies (comprising 157 patients) that reported the efficacy of percutaneous drainage in nonconsecutive patients with IPN. Outcome measures were the success of conservative management strategy, need for necrosectomy, and mortality. RESULTS There was significant heterogeneity in results among the studies. Based on a random effects model, conservative management was successful for 64% of patients (95% confidence interval [CI], 51%-78%); mortality was 12% (95% CI, 6%-18%), and 26% of patients required necrosectomy or additional surgery for complications (95% CI, 15%-37%). A separate analysis of 4 studies that reported outcomes of nonconsecutive patients with IPN following percutaneous drainage had comparable results; 50% had successful outcomes (95% CI, 43%-58%), mortality was 18% (95% CI, 6%-30%), and 38% of patients required surgery (95% CI, 20%-56%). CONCLUSIONS Conservative management without necrosectomy is a successful approach for 64% of patients with IPN. This approach has low mortality and prevents surgical necrosectomy.

Induction with NCB-02 (curcumin) enema for mild-to-moderate distal ulcerative colitis — A randomized, placebo-controlled, pilot study

BACKGROUND AND AIMS Curcumin, an active ingredient of turmeric with anti-inflammatory properties, has been demonstrated to be useful in experimental models of ulcerative colitis (UC). Its efficacy in humans needs to be investigated. METHODS A randomized, double-blind, single-centre pilot trial was conducted in patients with distal UC (<25 cm involvement) and mild-to-moderate disease activity. Forty-five patients were randomized to either NCB-02 (standardized curcumin preparation) enema plus oral 5-ASA or placebo enema plus oral 5-ASA. Primary end point was disease response, defined as reduction in Ulcerative Colitis Diseases Activity Index by 3 points at 8 weeks, and secondary end points were improvement in endoscopic activity and disease remission at 8 weeks. RESULTS Response to treatment was observed in 56.5% in NCB-02 group compared to 36.4% (p=0.175) in placebo group. At week 8, clinical remission was observed in 43.4% of patients in NCB-02 group compared to 22.7% in placebo group (p=0.14) and improvement on endoscopy in 52.2% of patients in NCB-02 group compared to 36.4% of patients in placebo group (p=0.29). Per protocol analysis revealed significantly better outcomes in NCB-02 group, in terms of clinical response (92.9% vs. 50%, p=0.01), clinical remission (71.4% vs. 31.3%, p=0.03), and improvement on endoscopy (85.7% vs. 50%, p=0.04). CONCLUSION In this pilot study we found some evidence that use of NCB-02 enema may tend to result in greater improvements in disease activity compared to placebo in patients with mild-to-moderate distal UC. The role of NCB-02 as a novel therapy for UC should be investigated further.

Effect of probiotic VSL#3 in the treatment of minimal hepatic encephalopathy: A non-inferiority randomized controlled trial.

Minimal hepatic encephalopathy (MHE) impairs daily functioning and health‐related quality of life in chronic liver disease (CLD). Lactulose is the standard treatment but has side‐effects. Probiotics have an encouraging role in MHE. The aim of the present study was to test whether probiotics are non‐inferior to lactulose in improving MHE.

Serum Human Trefoil Factor 3 is a Biomarker for Mucosal Healing in Ulcerative Colitis Patients with Minimal Disease Activity

BACKGROUND The goals of treating ulcerative colitis (UC) have shifted from clinical remission to mucosal healing. Non-invasive biomarkers are required to assess mucosal healing as endoscopic assessment is inconvenient for patients. Enhanced expression of trefoil factor 3 (TFF3, a mucin-associated peptide) is observed after injury of the gastrointestinal tract. The present study was designed to evaluate TFF3 as a biomarker of mucosal healing in patients with UC. METHODS This cross-sectional study included consecutive patients with UC (18-65 years old, disease duration >3 months, either left-sided colitis or pancolitis) who had a Simple Clinical Colitis Activity Index (SCCAI) <6. Colonoscopy was done to assess the presence or absence of mucosal healing (defined using the Baron score) in all patients. Serum level of TFF3 was assessed in all patients and 20 healthy controls. RESULTS Seventy-four patients were included [mean age 37.2±10.9 years, 47 males, median disease duration 4.8 years (IQR 3-8.3), median SCCAI = 0] in the study. Forty-three patients had mucosal healing (Baron score 0 or 1) and 31 did not (Baron score 2 or 3). Median TFF3 level in patients without mucosal healing was significantly higher than that in patients with mucosal healing [1.5 (IQR 1.2-1.9) vs 1.1 (IQR 0.8-1.3) ng/ml, p = 0.01] and healthy controls [0.85 (IQR 0.7-1.2) ng/ml, p < 0.001]. A serum TFF3 level of <1.27 ng/ml (as determined by the receiver operating characteristic curve; area under the curve 0.73) had sensitivity, specificity, positive predictive value and negative predictive value of 70, 68, 75 and 62%, respectively, for identifying patients with mucosal healing. CONCLUSION Serum TFF3 can potentially be used as a biomarker to assess mucosal healing in UC patients.

Accuracy of computed tomographic features in differentiating intestinal tuberculosis from Crohn's disease: a systematic review with meta-analysis

Abdominal computed tomography (CT) can noninvasively image the entire gastrointestinal tract and assess extraintestinal features that are important in differentiating Crohns disease (CD) and intestinal tuberculosis (ITB). The present meta-analysis pooled the results of all studies on the role of CT abdomen in differentiating between CD and ITB. We searched PubMed and Embase for all publications in English that analyzed the features differentiating between CD and ITB on abdominal CT. The features included comb sign, necrotic lymph nodes, asymmetric bowel wall thickening, skip lesions, fibrofatty proliferation, mural stratification, ileocaecal area, long segment, and left colonic involvements. Sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio (DOR) were calculated for all the features. Symmetric receiver operating characteristic curve was plotted for features present in >3 studies. Heterogeneity and publication bias was assessed and sensitivity analysis was performed by excluding studies that compared features on conventional abdominal CT instead of CT enterography (CTE). We included 6 studies (4 CTE, 1 conventional abdominal CT, and 1 CTE+conventional abdominal CT) involving 417 and 195 patients with CD and ITB, respectively. Necrotic lymph nodes had the highest diagnostic accuracy (sensitivity, 23%; specificity, 100%; DOR, 30.2) for ITB diagnosis, and comb sign (sensitivity, 82%; specificity, 81%; DOR, 21.5) followed by skip lesions (sensitivity, 86%; specificity, 74%; DOR, 16.5) had the highest diagnostic accuracy for CD diagnosis. On sensitivity analysis, the diagnostic accuracy of other features excluding asymmetric bowel wall thickening remained similar. Necrotic lymph nodes and comb sign on abdominal CT had the best diagnostic accuracy in differentiating CD and ITB.

Development and validation of visceral fat quantification as a surrogate marker for differentiation of Crohn's disease and Intestinal tuberculosis.

Crohns disease (CD) and intestinal tuberculosis (ITB) have close phenotypic resemblance. Mesenteric fat (a component of visceral fat [VF]) hypertrophy and fat wrapping, which is visible radiologically as fibrofatty proliferation, is seen more commonly in CD than in ITB.

Frequency, natural course and clinical significance of symptomatic terminal ileitis

Treatment guidelines for managing symptomatic terminal ileitis (TI) are lacking. We followed up a cohort of symptomatic TI patients to conduct an algorithm for their management.

Low dose oral curcumin is not effective in induction of remission in mild to moderate ulcerative colitis: Results from a randomized double blind placebo controlled trial

AIM To evaluate the role of oral curcumin in inducing clinical remission in patients with mild to moderate ulcerative colitis (UC). METHODS A prospective randomized double-blind placebo-controlled trial comparing the remission inducing effect of oral curcumin and mesalamine 2.4 g with placebo and mesalamine 2.4 g in patients of ulcerative colitis with mild to moderate severity was conducted from January 2003 to March 2005. The included patients received 1 capsule thrice a day of placebo or curcumin (150 mg) for 8 wk. Patients were evaluated clinically and endoscopically at 0, 4 and 8 wk. The primary outcome was clinical remission at 8 wk and secondary outcomes were clinical response, mucosal healing and treatment failure at 8 wk. The primary analysis was intention to treat worst case scenario (ITT-WCS). RESULTS Of 300 patients with UC, 62 patients (curcumin: 29, placebo: 33) fulfilled the inclusion criteria and were randomized at baseline. Of these, 21 patients did not complete the trial, 41 patients (curcumin: 16, placebo: 25) finally completed 8 wk. There was no significant difference in rates of clinical remission (31.3% vs 27.3%, P = 0.75), clinical response (20.7% vs 36.4%, P = 0.18), mucosal healing (34.5% vs 30.3%, P = 0.72), and treatment failure (25% vs 18.5%, P = 0.59) between curcumin and placebo at 8 wk. CONCLUSION Low dose oral curcumin at a dose of 450 mg/d was ineffective in inducing remission in mild to moderate cases of UC.

Prevalence and Association of Mycobacterium avium subspecies paratuberculosis with Disease Course in Patients with Ulcero-Constrictive Ileocolonic Disease

Background Association of Mycobacterium avium subspecies paratuberculosis (MAP) and Crohn’s disease (CD) has been controversial due to contradictory reports. Therefore, we determined the prevalence of MAP in patients with CD and intestinal tuberculosis (ITB) and its association with clinical course. Methodology Blood and intestinal biopsies were taken from 69 CD, 32 ITB patients and 41 patients with haemorrhoidal bleed who served as controls. qPCR targeting of MAP-specific IS900 gene was used to detect the presence of MAP DNA. qPCR results were further validated by sequencing. Immunohistochemistry (IHC) was used to detect the presence of MAP antigen in biopsy specimens. CD and ITB patients were followed-up for disease course and response to therapy. Principal Findings The frequency of MAP-specific DNA in biopsies by qPCR was significantly higher in CD patients (23.2%, p = 0.03) as compared to controls (7.3%). No significant difference in intestinal MAP presence was observed between ITB patients (12.5%, p = 0.6) and controls (7.3%). MAP presence in blood of CD patients was 10.1% as compared to 4.9% in controls while no patients with ITB were found to be positive (p = 0.1). Using IHC for detection of MAP antigen, the prevalence of MAP in CD was 2.9%, 12.5% in ITB patients and 2.4% in controls. However, long-term follow-up of the patients revealed no significant associations between clinical characteristics and treatment outcomes with MAP positivity. Conclusion We report significantly high prevalence of MAP in intestinal biopsies of CD patients. However, the presence of MAP does not affect the disease course and treatment outcomes in either CD or ITB patients.