Role of random biopsies in surveillance of dysplasia in ulcerative colitis patients with high risk of colorectal cancer

Background/AimsRecent data suggest that the incidence of ulcerative colitis (UC) related colorectal cancer (CRC) in India is similar to that of West. The optimum method for surveillance is still a debate. Surveillance with random biopsies has been the standard of care, but is a tedious process. We therefore undertook this study to assess the yield of random biopsy in dysplasia surveillance.MethodsBetween March 2014 and July 2015, patients of UC attending the Inflammatory Bowel Disease clinic at the All India Institute of Medical Sciences with high risk factors for CRC like duration of disease >15 years and pancolitis, family history of CRC, primary sclerosing cholangitis underwent surveillance colonoscopy for dysplasia. Four quadrant random biopsies at 10 cm intervals were taken (33 biopsies). Two pathologists examined specimens for dysplasia, and the yield of dysplasia was calculated.ResultsTwenty-eight patients were included. Twenty-six of these had pancolitis with a duration of disease greater than 15 years, and two patients had associated primary sclerosing cholangis. No patient had a family history of CRC. The mean age at onset of disease was 28.89±8.73 years and the duration of disease was 19.00±8.78 years. Eighteen patients (64.28%) were males. A total of 924 biopsies were taken. None of the biopsies revealed any evidence of dysplasia, and 7/924 (0.7%) were indefinite for dysplasia.ConclusionsRandom biopsy for surveillance in longstanding extensive colitis has a low yield for dysplasia and does not suffice for screening. Newer techniques such as chromoendoscopy-guided biopsies need greater adoption

Antihyperlipidemic and antiperoxidative effect of Diasulin, a polyherbal formulation in alloxan induced hyperglycemic rats

BACKGROUND: This study was undertaken to investigation the effect of Diasulin, a poly herbal drug composed of ethanolic extract of ten medicinal plants on blood glucose, plasma insulin, tissue lipid profile, and lipidperoxidation in alloxan induced diabetes. METHODS: Ethanolic extract of Diasulin a, poly herbal drug was administered orally (200 mg/kg body weight) for 30 days. The different doses of Diasulin on blood glucose and plasma insulin in diabetic rats were studied and the levels of lipid peroxides [TBARS, and Hydroperoxide] and tissue lipids [cholesterol, triglyceride, phospholipides and free fatty acids] were also estimated in alloxan induced diabetic rats. The effects were compared with glibenclamide. RESULT: Treatment with Diasulin and glibenclamide resulted in a significant reduction of blood glucose and increase in plasma insulin. Diasulin also resulted in a significant decrease in tissue lipids and lipid peroxide formation. The effect produced by Diasulin was comparable with that of glibenclamide. CONCLUSION: The decreased lipid peroxides and tissue lipids clearly showed the antihyperlipidemic and antiperoxidative effect of Diasulin apart from its antidiabetic effect

Are Truelove and Witts criteria for diagnosing acute severe colitis relevant for the Indian population? A prospective study

Background/Aims: Truelove and Witts criteria have been used to define acute severe colitis since the 1950s. However, hemoglobin (an additional criterion of the definition) levels in the general population in developing countries are lower than in the population of developed countries. We aimed to determine the relevance of Truelove and Witts criteria in the Indian population. Methods: Consecutive patients with acute severe colitis satisfying the Truelove and Witts criteria, hospitalized at a single center between April 2015 and December 2016 were included. All patients received intravenous corticosteroids and 16 required colectomy. The hemoglobin levels at admission were subsequently excluded from the classification criteria, and the effect this had on the criteria for diagnosis was determined. Results: Out of 61 patients of acute severe colitis diagnosed according to the original Truelove and Witts criteria, 12 patients (20%) had 1 additional criteri on, 33 (54%) had 2 additional criteria and 16 (26%) had 3 or more additional criteria in addition to 6 or more blood stained stools on admission. On excluding hemoglobin as an additional criterion from the Truelove and Witts definition, all patients still met the criteria for acute severe colitis. Conclusions: Truelove and Witts criteria can be used to define acute severe colitis in India, despite lower mean hemoglobin in the native population

Potential of fecal calprotectin as an objective marker to discriminate hospitalized patients with acute severe colitis from outpatients with less severe disease

Background Acute severe colitis (ASC) is conventionally diagnosed by Truelove and Witts’ criteria which are non-specific and can be affected by other pathologic conditions. Fecal calprotectin (FCP) is a gut-specific marker of inflammation which can predict short-term outcomes in patients with ASC. We aimed to define the role of FCP in the diagnosis of ASC. Methods This prospective observational cohort study included adult patients (> 18 years) with ulcerative colitis (UC) for whom FCP was measured and was under follow-up from April 2015 to December 2016. Patients were divided into two cohorts: (1) all consecutive hospitalized patients with ASC as defined by Truelove and Witts’ criteria; (2) outpatients with active UC (defined by Mayo score) who did not fulfill Truelove and Witts’ criteria. FCP levels were compared between the two cohorts, and a cutoff for FCP to diagnose ASC was determined. Results Of 97 patients, 49 were diagnosed with ASC (mean age: 36.1 ± 11.9 years, 36 males) and 48 with active UC (mean age: 37.9 ± 12.4 years, 25 males). Median FCP levels were significantly higher in patients with ASC [1776(952–3123) vs 282(43–568) µg/g, p < 0.001] than mild to moderately active UC (n = 48) or moderately active UC [n = 35, 1776(952–3123) vs 332(106–700) µg/g, p < 0.001]. A FCP cutoff of 782 μg/g of stool had excellent diagnostic accuracy, with an area under the curve of 0.92(95% CI 0.87–0.97), sensitivity of 84% and specificity of 88% to differentiate ASC from active UC. Conclusion FCP could differentiate ASC from mild to moderate patients with UC, but requires validation before clinical use

Faecal calprotectin and UCEIS predict short-term outcomes in acute severe colitis: Prospective Cohort Study

Early objective markers for failure of intravenous[iv] corticosteroid for acute severe colitis [ASC] can avoid delay in rescue therapy or colectomy. We investigated faecal calprotectin [FC], C-reactive protein [CRP], and endoscopy using the ulcerative colitis endoscopic index of severity [UCEIS] as predictors of steroid failure following intensive therapy of ASC.Consecutive patients with ASC satisfying Truelove and Witts' criteria, hospitalised at a single centre from May 2015 to November 2016, were included; all received iv corticosteroids. The primary outcome measure was steroid failure defined as colectomy and/or rescue therapy with ciclosporin or infliximab during admission. FC levels were measured at admission and on Day 3 of intensive therapy. UCEIS was scored at admission, and CRP on Day 3 of intensive therapy.Of 49 patients, 21 [43%] failed iv corticosteroids and 15 [31%] underwent surgery. FC levels were significantly higher in steroid failures (2522 [590-9654] µg/g) compared with steroid responders (1530 [352-10278] µg/g) at admission [p = 0.04], as well as on Day 3 of iv corticosteroid therapy (2718 [222-9175] µg/g vs 727 [218-4062] µg/g, p = 0.001). Steroid failures had a higher median [range] UCEIS score than responders (6 [4-8] vs 5 [4-7] [p = 0.001]). CRP level did not differ significantly between steroid failures and responders. A UCEIS &gt; 6 at admission and FC &gt; 1000 µg/g on Day 3 were independent predictors of steroid failure and need for rescue therapy/colectomy.All patients with UCEIS &gt; 6 and Day 3 FC &gt; 1000 µg/g failed iv corticosteroids. The UCEIS score on admission and Day 3 FC are early predictors of failure of ivcorticosteroid therapy

Are Truelove and Witts criteria for diagnosing acute severe colitis relevant for the Indian population? A prospective study

Background/Aims: Truelove and Witts criteria have been used to define acute severe colitis since the 1950s. However, hemoglobin (an additional criterion of the definition) levels in the general population in developing countries are lower than in the population of developed countries. We aimed to determine the relevance of Truelove and Witts criteria in the Indian population. Methods: Consecutive patients with acute severe colitis satisfying the Truelove and Witts criteria, hospitalized at a single center between April 2015 and December 2016 were included. All patients received intravenous corticosteroids and 16 required colectomy. The hemoglobin levels at admission were subsequently excluded from the classification criteria, and the effect this had on the criteria for diagnosis was determined. Results: Out of 61 patients of acute severe colitis diagnosed according to the original Truelove and Witts criteria, 12 patients (20%) had 1 additional criteri on, 33 (54%) had 2 additional criteria and 16 (26%) had 3 or more additional criteria in addition to 6 or more blood stained stools on admission. On excluding hemoglobin as an additional criterion from the Truelove and Witts definition, all patients still met the criteria for acute severe colitis. Conclusions: Truelove and Witts criteria can be used to define acute severe colitis in India, despite lower mean hemoglobin in the native population

Faecal calprotectin and UCEIS predict short-term outcomes in acute severe colitis: Prospective Cohort Study

Early objective markers for failure of intravenous[iv] corticosteroid for acute severe colitis [ASC] can avoid delay in rescue therapy or colectomy. We investigated faecal calprotectin [FC], C-reactive protein [CRP], and endoscopy using the ulcerative colitis endoscopic index of severity [UCEIS] as predictors of steroid failure following intensive therapy of ASC.Consecutive patients with ASC satisfying Truelove and Witts' criteria, hospitalised at a single centre from May 2015 to November 2016, were included; all received iv corticosteroids. The primary outcome measure was steroid failure defined as colectomy and/or rescue therapy with ciclosporin or infliximab during admission. FC levels were measured at admission and on Day 3 of intensive therapy. UCEIS was scored at admission, and CRP on Day 3 of intensive therapy.Of 49 patients, 21 [43%] failed iv corticosteroids and 15 [31%] underwent surgery. FC levels were significantly higher in steroid failures (2522 [590-9654] µg/g) compared with steroid responders (1530 [352-10278] µg/g) at admission [p = 0.04], as well as on Day 3 of iv corticosteroid therapy (2718 [222-9175] µg/g vs 727 [218-4062] µg/g, p = 0.001). Steroid failures had a higher median [range] UCEIS score than responders (6 [4-8] vs 5 [4-7] [p = 0.001]). CRP level did not differ significantly between steroid failures and responders. A UCEIS > 6 at admission and FC > 1000 µg/g on Day 3 were independent predictors of steroid failure and need for rescue therapy/colectomy.All patients with UCEIS > 6 and Day 3 FC > 1000 µg/g failed iv corticosteroids. The UCEIS score on admission and Day 3 FC are early predictors of failure of ivcorticosteroid therapy

Nuclear matrix binding protein SMAR1 regulates T-cell differentiation and allergic airway disease

Asthma is a complex airway allergic disease involving the interplay of various cell types, cytokines, and transcriptional factors. Though many factors contribute to disease etiology, the molecular control of disease phenotype and responsiveness is not well understood. Here we report an essential role of the matrix attachment region (MAR)-binding protein SMAR1 in regulating immune response during allergic airway disease. Conditional knockout of SMAR1 in T cells rendered the mice resistant to eosinophilic airway inflammation against ovalbumin (OVA) allergen with low immunoglobulin E (IgE) and interleukin-5 (IL-5) levels. Moreover, a lower IgE/IgG2a ratio and higher interferon-γ (IFN-γ) response suggested aberrant skewing of T-cell differentiation toward type 1 helper T cell (Th1) response. We show that SMAR1 functions as a negative regulator of Th1 and Th17 differentiation by interacting with two potential and similar MAR regions present on the promoters of T-bet and IL-17. Thus, we present SMAR1 as a regulator of T-cell differentiation that favors the establishment of Th2 cells by modulating Th1 and Th17 responses

Predictors of long-term outcomes in patients with acute severe colitis: A Northern Indian cohort study

Knowledge of long-term outcomes following an index episode of acute severe colitis (ASC) can help informed decision-making at a time of acute exacerbation especially when colectomy is an option. We aimed to identify long-term outcomes and their predictors after a first episode of ASC in a large North Indian cohort.Hospitalized patients satisfying Truelove and Witts' criteria under follow-up at a single centre from January 2003-December 2013 were included. Patients avoiding colectomy at index admission were categorized as complete (≤3 non bloody stool per day) or incomplete responders (CR, IR), based upon response to corticosteroids at day 7. Random Forest based machine learning models were constructed to predict the long term risk of colectomy or steroid dependence following an index episode of ASC.Of 1731 patients with ulcerative colitis, 179(10%) had an index episode of ASC. Nineteen(11%) patients underwent colectomy at index admission and 42(26%) over a median follow-up of 56(1-159) months. Hazard ratio for colectomy for IR was 3.6(1.7-7.5, p=0.001) compared to CR. Modeling based on four variables: response at day 7 of hospitalization, steroid use during first year of diagnosis, longer disease duration prior to ASC and number of extra-intestinal manifestations, was able to predict colectomy with an accuracy of 77%.Disease behavior of ASC in India is similar to the West, with a third undergoing colectomy at 10 years. Clinical features, especially response at day 7 hospitalization for index ASC, can predict both colectomy and steroid dependence with reasonable accuracy

Evaluation of Xpert MTB/RIF assay performance in the diagnosis of abdominal tuberculosis

Background/Aims: The use of genetic probes for the diagnosis of pulmonary tuberculosis (TB) has been well described. However, the role of these assays in the diagnosis of intestinal tuberculosis is unclear. We therefore assessed the diagnostic utility of the Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay, and estimated the prevalence of multidrug-resistant (MDR) TB in the Indian population.Methods: Of 99 patients recruited, 37 had intestinal TB; two control groups comprised 43 with Crohn's disease (CD) and 19 with irritable bowel syndrome. Colonoscopy was performed before starting any therapy; mucosal biopsies were subjected to histopathology, acid-fast bacilli staining, Lowenstein-Jensen culture, and nucleic acid amplification testing using the Xpert MTB/RIF assay. Patients were followed up for 6 months to confirm the diagnosis and response to therapy. A composite reference standard was used for diagnosis of TB and assessment of the diagnostic utility of the Xpert MTB/RIF assay.Results: Of 37 intestinal TB patients, the Xpert MTB/RIF assay was positive in three of 37 (8.1%), but none had MDR-TB. The sensitivity, specificity, positive predictive value, and negative predictive value of the Xpert MTB/RIF assay was 8.1%, 100%, 100%, and, 64.2%, respectively.Conclusions: The Xpert MTB/RIF assay has low sensitivity but high specificity for intestinal TB, and may be helpful in endemic tuberculosis areas, when clinicians are faced with difficulty differentiating TB and CD. Based on the Xpert MTB/RIF assay, the prevalence of intestinal MDR-TB is low in the Indian population