Adjuvant use of combination of antibiotics in acute severe ulcerative colitis: A placebo controlled randomized trial.

OBJECTIVES: Evaluation of a combination of antibiotics as an adjuvant therapy in acute severe ulcerative colitis (ASUC). METHODS: Patients with ASUC were randomized to either infusions of placebo or intravenous ceftriaxone and metronidazole in addition to standard care. Primary outcome was response on day three according to Oxford's criteria. Secondary outcome measures included changes in partial Mayo score, CRP levels, fecal calprotectin (day three), and need for second-line therapy, hospital stay, and mortality (day 28). RESULTS: Fifty patients (25 in each group, median age: 33 years, 23 males) were included. The number of patients with fulminant disease in the antibiotic group were 16 (64%) as compared to 7 (28%) in the standard of care group. Complete response on day three was attained by 7 (28%) in the antibiotic and 6 (24%) standard of care group (p = 1.00). Three patients from the antibiotic group underwent colectomy and three received intravenous cyclosporine whereas four patients in the standard of care group received cyclosporine (p = 0.725). There was no significant difference in change in CRP, Partial Mayo score, and fecal calprotectin between the two groups on day three. CONCLUSION: Combination of intravenous ceftriaxone and metronidazole did not improve outcomes in ASUC.Acronym: AAASUC trialRegistration Number: CTRI/2019/03/018196 and NCT03794765.

Serial measurements of faecal calprotectin may discriminate intestinal tuberculosis and Crohn's disease in patients started on antitubercular therapy.

BACKGROUND: Response to antitubercular therapy (ATT) is often used to differentiate intestinal tuberculosis (ITB) from Crohn's disease. Role of non-invasive biomarkers to predict mucosal response to ATT is unclear. MATERIALS AND METHODS: A prospective study to compare faecal calprotectin and serum C-reactive protein (CRP) levels at diagnosis, 2 and 6 months of ATT in patients with suspected ITB started on ATT was done. The patients were eventually divided into two groups: ITB or alternative diagnosis (OTH). Decline of calprotectin and CRP levels was used to compute area under the receiver operating characteristic (AUROC) to predict mucosal healing at 2 months. RESULTS: Thirty-seven patients (mean age: 34.95 ± 16.35 years, 23 males) were included and 28 (75.67%) were diagnosed as ITB while nine (24.32%) had alternative diagnosis (OTH). The median faecal calprotectin values of ITB and OTH groups at baseline, 2 months and 6 months were 216 and 282 µg/g (P = 0.466), 43 and 216 µg/g (P = 0.003), and 26 and 213 µg/g (P < 0.001), respectively. The median CRP values at baseline, 2 months and 6 months were 18 and 30 mg/L (P = 0.767), 4.7 and 15 mg/L (P = 0.025), and 3 and 10.85 mg/L (P = 0.068), respectively. The AUROC of percent decline in faecal calprotectin and serum CRP at 2 months for mucosal healing were 0.8287 [95% confidence inteval (CI) 0.6472-1] and 0.6018 (95% CI 0.4079-0.7957), respectively. CONCLUSION: Faecal calprotectin can help in assessing response to therapy in suspected ITB patients started on empirical ATT.

Relationship between Mayo endoscopic score and histological scores in ulcerative colitis: A prospective study.

BACKGROUND: The Mayo endoscopic score (MES) remains the most commonly used index in clinical practice, as well as in various clinical trials. Recently, two validated histological indices (Nancy Index [NI] and Robert Histological Index [RHI]) have been developed for ulcerative colitis (UC). We aim to study the relationship between MES with NI, RHI, and the established Geboes Index (GI) in patients with UC. METHODS: This was a prospective single-center study. MES was documented from the most involved area. Biopsy was taken from the same area and reported by a single gastrointestinal histopathologist who was blinded to the endoscopic score. Histological activity was reported using GI, NI, and RHI. Statistical analysis was performed using Spearman's correlation coefficient and Cohen's kappa coefficient using SPSS version 23. RESULTS: Median age of patients with UC (n = 96) was 36 years. Seventeen patients were in endoscopic remission (MES 0/1). Correlation coefficient between MES and GI/NI/RHI was only weak to moderate (rho = 0.381/0.389/0.442, respectively; P < 0.001 for all three correlations). In patients with endoscopic mucosal healing (n = 17), the agreement coefficient between MES and GI/RHI was weak (κ = 0.253/0.336, respectively; P = 0.001 for both agreements). However, there was no significant agreement coefficient between MES and NI (P = 0.573). CONCLUSION: MES moderately correlated with histological scores. RHI had the best correlation with MES among all histological indices. Endoscopic mucosal healing is not strongly correlated with histological healing. Histological examination should be performed even in patients with mucosal healing to detect ongoing histological activity.

Colonic mucosa-associated candida assessed by biopsy culture is associated with disease severity in ulcerative colitis: A prospective study.

OBJECTIVE: To evaluate the relationship of mucosa-associated candida (MAC) and disease severity in patients with ulcerative colitis (UC). METHODS: We prospectively investigated the presence, nature, and quantification of MAC in patients with UC and its relationship with disease severity. Consecutive patients with UC were assessed for clinical, endoscopic, histological features and serum markers of disease severity. All patients underwent mucosal brushing cytology, brushing culture, and biopsy culture for candida growth. MAC was considered present if mucosal biopsy culture grew candida. Candida spp. identification was performed by matrix-assisted laser desorption/ionization. Serum ß-D-glucan was measured with a Fungitell assay. Patients with irritable bowel syndrome who had undergone similar investigations were included as controls. RESULTS: Ninety-six patients with UC showed evidence of MAC more often than the controls (n = 20) based on biopsy culture (33.3% vs 5.0%, P = 0.011), brush cytology (30.2% vs 5.0%, P = 0.019), and brush culture (36.5% vs 10.0%, P = 0.021). Patients with UC had higher candida colony counts (≥103 CFU/mL) than controls (34.4% vs 5.0%, P = 0.007). Median ß-D-glucan values were higher in patients with UC than in controls (103.26 pg/mL vs 66.51 pg/mL, P = 0.011). The UC group with MAC had a higher median total Mayo score, C-reactive protein, fecal calprotectin, ß-D-glucan, and histological activity than those without MAC. CONCLUSIONS: Patients with UC more often show evidence of MAC and a higher candida colony count than controls. The presence of MAC is associated with high disease severity in patients with UC.

Epidemiology of gallbladder cancer in India.

India is a high incidence area for gallbladder cancer (GBC) and contributes to about 10% of the global GBC burden. Within India, the incidence is high in North, North-East, Central and Eastern India, and less common in South and West India. The incidence has been on a steady rise in both genders. The presentation is often with advanced disease and carries dismal prognosis. GBC in India usually affects younger patients in the 5th and 6th decade in contrast to the west. Gallstones are present in 80% of the Indian patients with GBC and its presence increases the vulnerability of the GB to mucosal injury. The incidence of GBC is out of proportion to the prevalence of gallstones in the country. Additional co-factors such as older age, lower socio-economic status, chronic Salmonella typhi (S. typhi) infection, Helicobacter pylori (H. pylori) infection, exposure to pollutants, heavy metals, chemicals, adulterated mustard oil and smoking in patients with gallstones have been identified which promote carcinogenesis. These risk factors act in tandem in an additive manner resulting in higher incidence of GBC as well as hasten the development of GBC. Environmental risk factors such as soil and water contamination by industrial wastes, agricultural effluents and human sewage have been identified as putative risk factors. Combination of a toxic environment, vulnerable GB and a susceptible host play a key role in the pathogenesis of GBC in the country. Large multicentric comprehensive studies are required in India to assess the attributable risk of each of the identified putative risk factors. This will help in formulating cost effective national strategies in preventing GBC related mortality in the country. Meanwhile a high index of suspicion to pick up incidental GBC, and improved access to healthcare facilities to manage GS appropriately will help in reducing GBC related mortality.

Oral Nano Vitamin D Supplementation Reduces Disease Activity in Ulcerative Colitis: A Double-Blind Randomized Parallel Group Placebo-controlled Trial.

INTRODUCTION: Vitamin D possesses anti-inflammatory properties and could be beneficial in ulcerative colitis (UC). METHODS: We studied the effect of oral nano vitamin D3 supplementation on disease activity in active UC [ulcerative colitis disease activity index (UCDAI)≥3]. Patients with active UC and vitamin D <40 ng/mL were randomized to receive either oral nano vitamin D (60,000 IU/d×8 d) or placebo. They were evaluated for disease activity (UCDAI scores, C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin) at baseline and reassessed at 4 weeks. The response was defined as a 3-point reduction in UCDAI score at 4 weeks and reduction in inflammatory markers. RESULTS: The median vitamin D levels increased from 15.4 to 40.83 mg/dL in vitamin D group (P≤0.001) and marginally from 13.45 to 18.85 mg/dL (P=0.027) in controls. The 3-point reduction in UCDAI was seen more often in vitamin D group as compared with the control (53% vs. 13%; P=0.001). Increase in vitamin D levels correlated with reduction in UCDAI score (P≤0.001; ρ=-0.713), C-reactive protein (P≤0.001; ρ=-0.603), and calprotectin (P=0.004; ρ=-0.368). Patients who achieved target vitamin D of >40 ng/mL (n=17) more often had a 3-point reduction in UCDAI (80% vs. 20%; P≤0.001) and reduction in grade of severity from 60% to 35% (P=0.038). Vitamin D administration (odds ratio, 9.17; 95% confidence interval, 2.02-41.67) and baseline histologic activity (odds ratio, 1.92; 95% confidence intervals, 1.2-3.08) independently predicted response. CONCLUSIONS: Oral nano vitamin D supplementation in active UC is associated with a reduction in disease activity and severity grade and is seen more often in those who achieved a target vitamin D level of 40 ng/mL.