Tofacitinib use in ulcerative colitis: An expert consensus for day-to-day clinical practice.

Rising number of inflammatory bowel disease (IBD) cases in developing countries necessitate clear guidance for clinicians for the appropriate use of advanced therapies. An expert consensus document was generated to guide the usage of tofacitinib, a Janus kinase inhibitor, in ulcerative colitis. Tofacitinib is a useful agent for the induction and maintenance of remission in ulcerative colitis. It can be used in the setting of biological failure or even steroid-dependent and thiopurine refractory disease. Typically, the induction dose is 10 mg BD orally. Usually, clinical response is evident within eight weeks of therapy. In those with clinical response, the dose can be reduced from 10 mg BD to 5 mg BD. Tofacitinib should be avoided or used cautiously in the elderly, patients with cardiovascular co-morbidity, uncontrolled cardiac risk factors, previous thrombotic episodes and those at high risk for venous thrombosis or previous malignancy. Baseline evaluation should include testing for and management of hepatitis B infection and latent tuberculosis. Where feasible, it is prudent to ensure complete adult vaccination, including Herpes zoster, before starting tofacitinib. The use of tofacitinib may be associated with an increased risk of infections such as herpes zoster and tuberculosis reactivation. Maternal exposure to tofacitinib should be avoided during pre-conception, pregnancy, and lactation. There is emerging evidence of tofacitinib in acute severe colitis, although the exact positioning (first-line with steroids or second-line) is uncertain.

Our experience with liver and spleen elastography in the prediction of oesophageal varices.

Background: Variceal bleeding is an important cause of mortality in patients with chronic liver disease (CLD). The gold standard for detection and grading of oesophageal varices (EV) is upper gastrointestinal endoscopy. However, it is expensive, time-consuming and invasive. Objectives: This study aimed to find any association between splenic shear wave velocity (SWV) measured by acoustic radiation force imaging (ARFI) and the presence of EV. Method: The quasi-experimental study included 50 patients with CLD and 50 subjects without CLD as the control group. Both underwent upper abdominal ultrasonography followed by elastographic assessment on a Siemens Acuson S2000TM ultrasound system. A comparison of the findings was made between the control and patient groups. Results: Both groups had similar hepatic size while patients with CLD had larger splenic size and area (p < 0.05). The CLD patients had higher mean hepatic and splenic SWV compared with the control group (p < 0.05). The mean splenic size and splenic SWV were higher in patients with varices than in those without varices (p < 0.05). Conclusion: Chronic liver disease causes significant increase in liver and splenic stiffness with splenic SWV values being higher for patients with varices emphasising the role of elastography as a non-invasive predictor for the presence of EVs. Splenic SWV had the highest sensitivity and specificity, which was augmented by a combination of hepatic and splenic SWV. Thus, splenic SWV alone or in combination with hepatic SWV is a useful technique for prediction of the presence of EVs. Contribution: This study aims to find an alternative non-invasive and cost-effective technique for screening of EV.

The Role of Yeast Probiotics in Gastrointestinal Conditions: An Overview.

The human gut is home to a variety of microbes, including bacteria, viruses, fungi, eukaryotes, and archaea, which together form a complex structure. In general, the microbiota that colonizes the gastrointestinal (GI) tract plays a significant role in maintaining human health and has been implicated in the pathogenesis of a number of GI illnesses. The structural integrity and metabolic processes of the alimentary canal are physiologically influenced by the dynamic interactions between the gut and bacteria. GI dysbiosis is a result of an imbalance brought on by a decline in microbial diversity, the loss of helpful bacteria, and an increase in pathobionts. It is crucial to restoring the gut microbiota. In order to regain the eubiotic state of the microbial flora, varied methods are being researched and implemented. The use of probiotics is one strategy for re-establishing healthy gut flora. Probiotics are "living microorganisms" that improve the health of the host when provided in adequate quantities. There are two types of probiotics-bacteria and yeast-based. The review will look at and summarize the information for yeast-based Saccharomyces probiotics regarding their effectiveness and safety in treating a variety of patient diseases, particularly irritable bowel syndrome (IBS), antibiotic-associated diarrhea, and Heliobacter pylori (HpSA) infection. The only commercially accessible yeast probiotic, the Saccharomyces strain, which consists of Saccharomyces cerevisae (S. cerevisiae) and Saccharomyces boulardii (Sb), provides a number of benefits over bacterial probiotics. The significance of Sb as a potent biotherapeutic medication that may be utilized to prevent or treat a variety of GI disorders has been substantiated by several experimental studies and clinical trials.

Segmental filiform-polyposis in a treated case of ulcerative colitis, colon: An unusual presentation raising a doubt of primary diagnosis?

Inflammatory bowel disease is broadly classified into Crohn's disease and ulcerative colitis. The standard criteria to distinguish between the two is the manner of the involvement of the bowel, with the former showing classical skip lesions and the latter having continuous involvement of the colon, most commonly affecting the rectum. However, some cases exhibit overlapping features. Herein, we report a treated case of ulcerative colitis presenting with patchy involvement of the colon in the form of peculiar segmental filiform polyposis spanned abruptly by an intervening normal mucosa. The clinico-radiologically suspicion of carcinoma colon with Crohn's colitis was considered. The clinicians and pathologists must be aware of such atypical presentations and should not be misled to change the diagnosis from ulcerative colitis to Crohn's colitis on the post-treatment resection specimens or endoscopic biopsies solely in view of the patchy filiform polyposis (FP), which poses a drastic impact on the patient's management.

Comparing Myelosuppression Frequency in Indian Inflammatory Bowel Disease Patients: A Randomized Trial of Full Dose Versus Gradual Escalation of Thiopurines.

INTRODUCTION: We aimed to compare the frequency of myelosuppression in patients initiating azathioprine (AZA) at full dose versus those undergoing gradual dose escalation. METHODS: Forty patients with inflammatory bowel disease were recruited over one year and randomized into two groups of 20. Group A initiated AZA at a full dose of 2 mg/kg, while group B started at 1 mg/kg with subsequent dose increases at regular intervals. RESULTS: Seventeen patients from each group were included in the final analysis. During follow-up, two patients (11.8%) from group A and four patients (23.5%) from group B experienced relapses (p=0.65). Myelosuppression occurred in two patients (11.8%) from each group. Absolute neutrophil counts in group A tended to have lower median values than those in group B, particularly four weeks after AZA initiation. Univariate analysis identified serum proteins, albumin, and bilirubin as significantly associated with leukopenia, but these factors were not significant according to multivariate analysis. CONCLUSIONS: The incidence of myelosuppression was similar between the groups. Patients with full-dose initiation of AZA had numerically fewer relapses during the follow-up period.

Asian-Pacific consensus on small intestinal bacterial overgrowth in gastrointestinal disorders: An initiative of the Indian Neurogastroenterology and Motility Association.

In the clinical setting, small intestinal bacterial overgrowth (SIBO) is a frequent, but under-diagnosed entity. SIBO is linked to various gastrointestinal (GI) and non-GI disorders with potentially significant morbidity. The optimal management of SIBO is undefined while there is a lack of published consensus guidelines. Against this background, under the auspices of the Indian Neurogastroenterology and Motility Association (INMA), formerly known as the Indian Motility and Functional Diseases Association (IMFDA), experts from the Asian-Pacific region with extensive research and clinical experience in the field of gut dysbiosis including SIBO developed this evidence-based practice guideline for the management of SIBO utilizing a modified Delphi process based upon 37 consensus statements, involving an electronic voting process as well as face-to-face meetings and review of relevant supporting literature. These statements include 6 statements on definition and epidemiology; 11 on etiopathogenesis and pathophysiology; 5 on clinical manifestations, differential diagnosis, and predictors; and 15 on investigations and treatment. When the proportion of those who voted either to accept completely or with minor reservations was 80% or higher, the statement was regarded as accepted. The members of the consensus team consider that this guideline would be valuable to inform clinical practice, teaching, and research on SIBO in the Asian-Pacific region as well as in other countries.

Efficacy of hepatitis B vaccination in patients with ulcerative colitis: a prospective cohort study.

BACKGROUND/AIMS: Response to vaccine in patients with inflammatory bowel disease is lower than in the general population. We aimed to evaluate the efficacy of hepatitis B virus (HBV) vaccination in patients with ulcerative colitis (UC) versus controls. METHODS: We prospectively compared antibody response to HBV vaccination in 100 patients with UC versus controls. HBV vaccination was given to all the cases and controls at 0, 1 and 6 months. Anti-hepatitis B surface (anti-HBs) titers were then measured 4 weeks after the first and the third dose. Adequate immune response (AIR) was considered if the anti-HBs titer was >10 IU/L and effective immune response (EIR) if the anti-HBs titer was >100 IU/L. RESULTS: Median anti-HBs titer was lower in patients with UC than controls (67 IU/L vs. 105 IU/L, P<0.01). AIR and EIR were significantly lower in patients than in controls (82% vs. 96%, P=0.001; 41% vs. 66%, P<0.001, respectively). Univariate analysis showed that age <30 years, mild to moderate severity of disease, disease duration <5 years, male sex, post first dose anti-HBs titer >2 IU/L and non-exposure to corticosteroids, azathioprine and biologicals were predictors of AIR in patients with UC (P<0.05). Multivariate analysis revealed that only non-exposure to corticosteroids, azathioprine and biologicals, male sex, and disease duration <5 years were independent predictors of AIR. CONCLUSIONS: Response rate to the HBV vaccination in patients with UC was significantly lower as compared to the controls. Male sex, shorter disease duration, and non-exposure to immunomodulators were independent predictors of AIR.

Endoscopic retrograde cholangiopancreaticography-related complications - Experience from tertiary care teaching centre over half a decade.

Introduction: Endoscopic retrograde cholangiopancreaticography (ERCP) is an essential therapeutic procedure with a significant risk of complications. Data regarding the complications and predictors of adverse outcomes such as mortality are scarce, especially from India and Asia. We aimed to look at the incidence and outcome of complications in ERCP patients. Materials and Methods: This study is a retrospective analysis of prospectively collected data of all the patients who underwent ERCP and had a complication from January 2012 to December 2018. Data were recorded in predesigned pro forma. The data analysis was done by appropriate statistical tests. Results: : A total of 17,163 ERCP were done. A total of 570 patients (3.3%) had complications; perforation (n = 275, 1.6%) was most common followed by pancreatitis (n = 177, 1.03%) and bleeding (n = 60, 0.35%). The majorities of perforations were managed conservatively (n = 205, 74.5%), and 53 (19%) required surgery. Overall, 69 (0.4%) patients died. Of these, 30 (10.9%) patients died with perforation. Age (odds ratio [OR]: 1.04, 95% confidence interval [CI]: 1.005-1.07) and need of surgery (OR: 5.11, 95% CI: 1.66-15.77) were the predictors of mortality in patients with perforation. The majority pancreatitis were mild (n = 125, 70.6%) and overall mortality was 5.6% (n = 10). Conclusion: ERCP complications have been remained static over the years, with perforation and pancreatitis contributing the most. Most perforations can be managed conservatively with good clinical outcomes.

Evaluation of the Utility of Amino Acid Citrulline as a Surrogate Metabolomic Biomarker for the Diagnosis of Celiac Disease.

INTRODUCTION: Citrulline is regarded as a biomarker for celiac disease (CD). Its utility for assessment and evaluation of additive predictive value for latent, potential CD and first degree relatives (FDRs) needs exploration. METHOD: Consecutive 558 index cases diagnosed as per European Society for Pediatric Gastroenterology and Nutrition (ESPGHAN) 2012 guidelines and their 1565 FDRs were evaluated over five and half year period. Serology negative FDRs at initial visit and follow ups were served as controls. HLA typing for DQ2 and DQ8 genotypes, along with plasma and dried blood spot (DBS) filter paper citrulline were evaluated. RESULTS: Median plasma citrulline values were 20.1 and 37.33 µMol/l in cases and controls (P < .001). Cut off values for Marsh grade 3a, 3b, and 3c were 35.0, 32.8, 25.26 µMol/l in CD patients and 36.51, 30.10, 25.26 µMol/l in biopsy proven FDR. Increasing trends of plasma citrulline levels with decreasing tTG-IgA levels were observed on follow up. Low plasma citrulline levels were observed with HLA DQ 2.5 genotype (P < .05). Agreement between DBS and plasma citrulline was 94.8%. CONCLUSION: Citrulline is a good surrogate biomarker for identification of histopathological grade of damage, extent of mucosal recovery and has negative correlation with tTG-IgA. It identifies the silent and latent phase of CD. DBS citrulline provides adequate information and can be used for monitoring CD patients at remote locations.

Tacrolimus as rescue therapy for steroid-dependent/steroid-refractory ulcerative colitis: Experience from tertiary referral center in India.

INTRODUCTION: Between 20% and 40% of patients with severe ulcerative colitis (UC) are either steroid-refractory UC (SRUC) or steroid-dependent UC (SDUC). Tacrolimus is an oral and relatively inexpensive drug, which has been extensively used in Japan for steroid-refractory and steroid-dependent disease. METHODS: Patients diagnosed with SDUC/SRUC were treated with tacrolimus 0.05-0.1 mg/kg in this prospective study. Clinical Mayo score (CMS) and UC Endoscopic Index of Severity (UCEIS) were evaluated prior to starting the drug and subsequently after 8 weeks. 5-Aminosalicylic acid agents (5-ASA) and immunomodulators were continued if the patients were previously on these drugs. Clinical response at 8 weeks was defined as decrease in CMS by at least 3 points. Clinical remission was defined as CMS ≤2 and combined remission as CMS≤2 with UCEIS <3. RESULTS: Fifty-two patients (29 males) with a mean age of 35.1± 12.8 years with predominantly E3 disease (71%) were prospectively evaluated in this study. SDUC and SRUC were diagnosed in 31 and 21 patients, respectively. Seven failed treatment within 8 weeks, four were subjected to surgery, and 3 were switched to infliximab. Forty-two patients continued tacrolimus for 8 weeks. Mean CMS and UCEIS prior to starting tacrolimus were 6 ± 1.1 and 4.8 ± 1.1, respectively. At 8 weeks, median CMS and UCEIS decreased to 2.6 ± 1.7 and 2.7 ± 1.3, respectively. Clinical response was documented in 29 patients (56%) at week 8 whereas clinical remission was seen in 25 patients (48%). Combined clinical and endoscopic remissions were seen in 18 patients (35%). Except for a single  patient who developed reversible renal dysfunction, no other adverse event was  observed. CONCLUSION: Our results show that tacrolimus is effective in inducing a clinical response in 56% of patients with SDUC and SRUC. In view of its low cost and safety profile, it may be considered first-line therapy for SDUC/SRUC.

Reappraisal of the Role of Ascitic Fluid Adenosine Deaminase for the Diagnosis of Peritoneal Tuberculosis in Cirrhosis.

BACKGROUNDS/AIMS: Although peritoneal tuberculosis (TB) is one of the important differential diagnoses among cirrhotic patients with ascites, a peritoneal biopsy is not always available. High ascitic fluid adenosine deaminase (ADA) has been indicative of peritoneal TB. On the other hand, studies to assess its diagnostic utility based on the confirmation of peritoneal biopsy in cirrhotic patients are scarce. METHODS: Patients with new-onset ascites were enrolled prospectively from a tertiary hospital. Peritoneal biopsy was applied according to clinical judgment when required. Based on pathology diagnosis of the peritoneum, the diagnostic efficacy of ascitic fluid ADA for peritoneal TB was evaluated in total and cirrhotic patients, respectively. RESULTS: Among 286 patients enrolled, 78 were diagnosed with peritoneal TB. One hundred and thirty-two patients had cirrhosis, and 30 of those were diagnosed with peritoneal TB. The mean ADA was 72.2 U/L and 22.7 U/L in the peritoneal and non-peritoneal TB group, respectively, among the total study population, and 64.0 U/L and 19.1 U/L in the peritoneal and non-peritoneal TB group, respectively, among the subgroup with cirrhosis. The area under the curve for ADA to diagnose peritoneal TB was 0.96 in the total study population with a cutoff value of 41.1 U/L, and 0.93 in cirrhotic patients with a cutoff value of 39.9 U/L. CONCLUSIONS: The ascitic fluid ADA measurements showed high diagnostic performance for peritoneal tuberculosis in patients with ascites regardless of cirrhosis at a similar cutoff value.

Comparison of Interferon-Gamma Release Assay and Tuberculin Skin Test for the Screening of Latent Tuberculosis in Inflammatory Bowel Disease Patients: Indian Scenario.

BACKGROUND: In a country like India, where the prevalence of tuberculosis is very high, the role of screening tools for detection of latent tuberculosis infection (LTBI) like TST and IGRA is still unclear, especially in inflammatory bowel disease (IBD) patients. Our study is aimed at comparing the interferon-gamma release assay (IGRA) and tuberculin skin test (TST) to determine the prevalence of LTBI in IBD patients in the Indian subset of the population. METHODS: It was a prospective observational analysis. A total of 257 participants were included in the study. Both TST and IGRA were performed in consecutive patients diagnosed with IBD (131 patients) and in 126 healthy individuals. Both tests were performed on the same day. LTBI diagnosis was considered if any one of TST or IGRA was found to be positive. RESULTS: Out of 131 IBD patients, 121 patients had ulcerative colitis and 10 patients had Crohn's disease. 29% of the IBD patients and 22% of the control subjects had LTBI. The study demonstrated concordance between TST and IGRA. Agreement test kappa value for IBD patients was 0.656 (CI 0.50-0.81), with a p value of <0.001, suggestive of a fair agreement. Mean IFN-γ release was lower in the immunosuppressed group as compared to non-immunosuppressed individuals (0.26 ± 0.17 vs. 0.45 ± 0.07, p = 0.02). Cohen's kappa coefficient values in IBD cases and control subjects were 0.66 and 0.79, respectively. TST was found to be negatively correlated to BMI. CONCLUSION: Agreement between TST and IGRA was fair in IBD patients. For LTBI screening in IBD patients, TST and IGRA are complementary methods.

Colitis and Crohn's Foundation (India): a first nationwide inflammatory bowel disease registry.

BACKGROUND/AIMS: The national registry for inflammatory bowel disease (IBD) was designed to study epidemiology and prescribing pattern of treatment of IBD in India. METHODS: A multicenter, cross-sectional, prospective registry was established across four geographical zones of India. Adult patients with ulcerative colitis (UC) or Crohn's disease (CD) were enrolled between January 2014 and December 2015. Information related to demographics; disease features; complications; and treatment history were collected and analyzed. RESULTS: A total of 3,863 patients (mean age, 36.7 ± 13.6 years; 3,232 UC [83.7%] and 631 CD [16.3%]) were enrolled. The majority of patients with UC (n = 1,870, 57.9%) were from north, CD was more common in south (n = 348, 55.5%). The UC:CD ratio was 5.1:1. There was a male predominance (male:female = 1.6:1). The commonest presentation of UC was moderately severe (n = 1,939, 60%) and E2 disease (n = 1,895, 58.6%). Patients with CD most commonly presented with ileocolonic (n = 229, 36.3%) inflammatory (n = 504, 79.9%) disease. Extraintestinal manifestations were recorded among 13% and 20% of patients in UC and CD respectively. Less than 1% patients from both cohorts developed colon cancer (n = 26, 0.7%). The commonly used drugs were 5-aminosalicylates (99%) in both UC and CD followed by azathioprine (34.4%). Biologics were used in only 1.5% of patients; more commonly for UC in north and CD in south. CONCLUSIONS: The national IBD registry brings out diversities in the 4 geographical zones of India. This will help in aiding research on IBD and improving quality of patient care.

Role of linear endosonography in the diagnosis of biopsy-negative malignant esophageal strictures: Exploring the unexplored.

BACKGROUND AND AIM: Endoscopic biopsy is standard for the diagnosis of esophageal malignancy. However, few cases present with smooth stricture with repetitive negative biopsy results. We aimed to use linear endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) in the diagnosis of biopsy-negative suspected malignant esophageal strictures. METHODS: We retrospectively analyzed the data from August 2017 to December 2018 of biopsy-negative esophageal strictures. All adult patients with twice-negative biopsies and with smooth overlying esophageal mucosa on endoscopy were included. Clinical, epidemiological, endoscopic, imaging, and EUS findings were noted and analyzed. RESULTS: Eighteen patients underwent EUS for suspicion of malignant esophageal stricture. Seven were excluded as they were submucosal tumors. Eleven patients showed the presence of malignancy on EUS FNA samples. Nine were males. Computed tomography showed esophageal wall thickening in eight (16-38 mm) and esophageal mass in three patients. EUS showed loss of a normal five-layered wall structure of the esophagus in all patients. Fine-needle aspiration cytology demonstrated squamous cell carcinoma (n = 4), adenocarcinoma (n = 4), poorly differentiated carcinoma (n = 2), and neuroendocrine carcinoma (n = 1). There were no complications. CONCLUSION: EUS with FNA is effective and safe for the diagnosis of biopsy-negative malignant esophageal strictures.