Endoscopic Glue Injection vs Glue Plus BRTO or TIPSS for Preventing Gastric Variceal Bleeding: A Randomized Controlled Trial.

BACKGROUND AND AIMS: The study sought to compare the efficacy of endoscopic injection sclerotherapy with cyanoacrylate glue (EIS-CYA) vs EIS-CYA plus a radiologic intervention (RI) (either transjugular intrahepatic portosystemic shunt or balloon-occluded retrograde transvenous obliteration) for secondary prophylaxis in patients with liver cirrhosis who presented with acute variceal bleeding from cardiofundal varices. Primary outcome measure was gastric varix (GV) rebleed rates at 1 year. METHODS: Consecutive cirrhosis patients with acute variceal bleeding from cardiofundal varices were randomized into 2 arms (45 in each) after primary hemostasis by EIS-CYA. In the endoscopic intervention (EI) arm, EIS-CYA was repeated at regular intervals (1, 3, 6, and 12 months), while in the RI arm, patients underwent transjugular intrahepatic portosystemic shunt or balloon-occluded retrograde transvenous obliteration followed by endoscopic surveillance. RESULTS: GV rebleed rates at 1 year were higher in the EI arm compared with the RI arm: 11 (24.4%; 95% confidence interval [CI], 12.9%-39.5%) vs 1 (2.2%; 95% CI, 0.1%-11.8%) (P = .004; absolute risk difference: 22.2%; 95% CI, 8.4%-36.6%). GV rebleed-related mortality in the EI arm (8 [17.8%; 95% CI, 8.0%-32.1%]) was significantly higher than in the RI arm (1 [2.2%; 0.1%-11.8%]) (P = .030; absolute risk difference: 15.6; 95% CI, 2.9%-29.2%); however, there was no difference in all-cause mortality between the 2 groups (12 [26.7%; 95% CI, 14.6%-41.9%] vs 7 [15.6%; 95% CI, 6.5%-29.5%]). The number needed to treat to prevent 1 GV-related rebleed at 1 year was 4.5. CONCLUSIONS: RI for secondary prophylaxis reduces rebleeding from GV and GV rebleeding-related mortality in patients with GV hemorrhage. (CTRI/2021/02/031396).

Coconut Water Induces Clinical Remission in Mild to Moderate Ulcerative Colitis: Double-blind Placebo-controlled Trial.

BACKGROUND & AIMS: Coconut water (CW) is anti-inflammatory, can manipulate the gut microbiome, and is a rich source of potassium. Gut microbiome modulation improves outcomes in ulcerative colitis (UC), and potassium possesses in vitro anti-inflammatory property. We evaluated the effect of CW as an adjunct therapy for patients with mild-moderate UC. METHODS: This single-center, double-blind, placebo-controlled trial randomized patients with mild to moderate (Simple Clinical Colitis Activity Index [SCCAI]: 3-9) endoscopically active UC (Ulcerative Colitis Endoscopic Index of Severity [UCEIS] >1) in 1:1 ratio to CW + standard medical therapy (SMT) vs placebo + SMT. Four hundred mL of CW was administered for 8 weeks. Primary outcome measure was clinical remission (SCCAI ≤2), and secondary outcome measures were clinical response (SCCAI decline ≥3) and adverse events at 8 weeks. Microbiome was analyzed at baseline and 8 weeks. RESULTS: Of 121 patients screened, 95 were included for modified intention to treat analysis (CW, n = 49; placebo, n = 46) (mean age, 37.2 ± 11.2 years; males, 54.1%; disease duration, 48 months [interquartile range (IQR), 24-90 months]; pancolitis, 26.1%; SCCAI, 5 [IQR, 4-6]; UCEIS, 4 [IQR, 3-5]). Clinical response (57.1% vs 28.3%; odds ratio [OR], 3.4; 95% confidence interval [CI], 1.4-7.9; P = .01), remission (53.1% vs 28.3%; OR, 2.9; 95% CI, 1.2-6.7; P = .02), and proportion of patients with fecal calprotectin (FCP) <150 µg/g (30.6% vs 6.5%; OR, 6.3; 95% CI, 1.7-23.6; P = .003) were significantly higher in CW. The relative abundance of bacterial taxa that had a significant or trend towards negative correlation with SCCAI, UCEIS, or FCP increased at 8 weeks in CW, and this effect was independent of disease activity and dietary fiber. Adverse events were comparable, and no patient developed hyperkalemia. CONCLUSIONS: CW was more effective than placebo for induction of clinical remission in patients with mild to moderate UC. The trial was prospectively registered on Clinical Trials Registry of India (ctri.nic.in, Number: CTRI/2019/03/01827).

New diagnostic strategies to distinguish Crohn's disease and gastrointestinal tuberculosis.

PURPOSE OF REVIEW: Despite advances in our radiological, histological and microbiological armamentarium, distinguishing between Crohn's disease (CD) and intestinal tuberculosis (ITB), especially in a TB endemic country, continues to be a challenging exercise in a significant number of patients. This review aims to summarize current available evidence on novel diagnostic techniques which have a potential to fill the gap in our knowledge of differentiating between ITB and CD. RECENT FINDINGS: Both ITB and CD are associated with altered host immune responses, and detection of these altered innate and adaptive immune cells has potential to distinguish ITB from CD. ITB and CD have different epigenetic, proteomic and metabolomic signatures, and recent research has focused on detecting these differences. In addition, the gut microbiome, which is involved in mucosal immunity and inflammatory responses, is considerably altered in both ITB and CD, and is another potential frontier, which can be tapped to discriminate between the two diseases. With technological advancements, we have newer radiological modalities including perfusion CT and dual-layer spectral detector CT enterography and evidence is emerging of their role in differentiating ITB from CD. Finally, time will tell whether the advent of artificial intelligence, with rapidly accumulating data in this field, will be the gamechanger in solving this puzzle of diagnostic dilemma between ITB and Crohn's disease. SUMMARY: Recent advances need to be clinically validated before they can be used as novel diagnostic measures to differentiate Intestinal TB from CD.

Efficacy of Rifaximin in Patients With Abdominal Bloating or Distension: A Systematic Review and Meta-analysis.

BACKGROUND: Abdominal bloating is a common complaint in patients with functional and organic bowel disease. Rifaximin, a nonabsorbable antibiotic, has been tried for the treatment of this disease. We performed a systematic review and meta-analysis to study the efficacy of rifaximin in abdominal bloating and distension in patients with functional gastrointestinal disorders (FGID). METHODS: We accessed 4 databases (MEDLINE, Embase, SCOPUS, and Web of Science) to identify randomized placebo-controlled trials that utilized rifaximin in FGID. We excluded observational studies, those including patients with organic bowel disorders such as inflammatory bowel diseases, or those in which rifaximin was given for other indications, such as hepatic encephalopathy. RESULTS: A total of 1426 articles were available, of which 813 articles were screened after removing duplicates and 34 articles were selected for full-text review. Finally, 10 trials (3326 patients) were included. Rifaximin was administered in doses ranging from 400 to 1650 mg per day for 1 to 2 weeks. Rifaximin therapy led to a higher likelihood of improvement in symptoms of bloating (44.6% vs. 34.6%, RR 1.22, 95% CI 1.11, 1.35; n=2401 patients) without significant heterogeneity. However, daily doses less than 1200 mg/day were similar to placebo ( P =0.09). Bloating was quantified subjectively in 7 studies, and rifaximin led to a greater reduction in bloating scores compared with placebo (standardized mean difference -0.3, 95% CI -0.51, -0.1, P =0.04) but carried significant heterogeneity ( I2 =61.6%, P =0.01). CONCLUSIONS: Rifaximin therapy is associated with an increased likelihood of improvement in bloating and distension, as well as reduces the subjective severity of these symptoms in patients with FGID.

High prevalence of multi-drug resistant organisms in the gut flora of healthy rural individuals in northern India.

Background & objectives Presence of resistant gut flora in the community is associated with increasing multi-drug resistance (MDR) infections. In this study, the prevalence of MDR organisms in the gut flora of a healthy rural population residing in northern India was determined. Methods Healthy individuals aged 18-45 yr from Nuh district, Haryana, India were included in this study. Risk factors associated with dysbiosis, diet, lifestyle and exposure to animals was assessed. Qualitative food frequency questionnaire and inflammatory diet score was calculated. Pathogens in stool sample were detected by MALDI-TOF. Evaluation of antimicrobial susceptibility was done by automated Vitek-2 System. The presence of antimicrobial resistance (AMR) genes was evaluated using PCR. An isolate having resistance to at least one antibiotic out of the three or more classes of antibiotics tested was labelled as MDR. Results Among 153 individuals included in this study (mean age-32.5±8.6 yr, females-58.2%, vegetarian-68.6%), the most frequent organism isolated was E. coli (n=137, 89.5%) followed by K. pneumoniae (n=19, 12.4%) and Enterobacter species (n=23, 15%). Forty seven (30.7%) individuals had sensitive and 42 (27.4%) had MDR organisms. Fifty one (33.3%) were positive for ESBL, 5 (3.3%) were positive for carbapenems, and 18 (11.8%) were positive for both genes. Age, gender, body mass index, diet pattern, or diet score were similar between participants with sensitive and resistant organisms. Resistance against fluoroquinolones was highest [92(48.7%)] among all isolates. Forty nine (25.9%), 25 (13.2%), 24 (12.7%) and 21 (11.1%) isolates, respectively were positive for blaTEM, blaSHV, blaCTXM-1 and OXA-48 genes. Interpretation & conclusions Overall the study findings suggest that 27 per cent individuals from rural northern India carry MDR organisms in their fecal flora, with an ESBL carriage rate of 44 per cent.

Incidence of intestinal & extra-intestinal cancers among individuals with Crohn's disease in northern India.

Background & objectives Crohn's disease (CD) is associated with a higher risk of malignancy, which is attributed to disease behaviour and the usage of immunosuppressants. The burden of malignancy in CD is scarcely reported from Asia. We report real-world data on CD-related malignancy from a northern Indian cohort. Methods This retrospective analysis included individuals with CD who were followed up at the All India Institute of Medical Sciences, New Delhi, from 2005 to 2021. The standardized incidence ratio (SIR) was used to calculate the relative risk of malignancy in CD affected individuals compared to the general population. Results In this study, 952 study participants were included, with a mean age at diagnosis of 36.9±15.11 yr; 61.1 per cent were male. The median follow-up duration was 34 months [IQR (interquartile range): 19-73]. Most study participants received steroids (76.7%), immunomodulators (68.7%), or anti-TNF therapy (10.8%). The overall incidence of malignancy was 1.05 per cent, indicating a 10.45 times higher risk in CD [SIR: 10.45; 95% Confidence interval (CI):4.98-17.96]. Eight out of 826, 1 of 106 and 1 of 25 study participants developed malignancy in the first, second and third decades, respectively. The cumulative risk of malignancy was 2.7, 5.5, and 13.4 per cent in the first, second, and third decades, respectively. Regarding bowel malignancies, one study participant each developed ileocaecal adenocarcinoma, anorectal adenocarcinoma, malignant rectal fibrous histiocytoma, and gastric adenocarcinoma. Extraintestinal malignancies included single cases each of follicular neoplasia of the thyroid, neuroendocrine tumour of the pancreatic tail, breast cancer, hepatocellular cancer, oral cancer, and prostate cancer. No cases of lymphoma or skin malignancy were reported. Interpretation & conclusions At 30 yr, the cumulative risk of malignancy among Indian CD-affected individuals was 13.4 per cent, with a SIR of 10.45 (95% CI: 4.98- 17.96). The risk increased with increasing age at disease onset and duration.

An epithelial Nfkb2 pathway exacerbates intestinal inflammation by supplementing latent RelA dimers to the canonical NF-κB module.

Aberrant inflammation, such as that associated with inflammatory bowel disease (IBD), is fueled by the inordinate activity of RelA/NF-κB factors. As such, the canonical NF-κB module mediates controlled nuclear activation of RelA dimers from the latent cytoplasmic complexes. What provokes pathological RelA activity in the colitogenic gut remains unclear. The noncanonical NF-κB pathway typically promotes immune organogenesis involving Nfkb2 gene products. Because NF-κB pathways are intertwined, we asked whether noncanonical signaling aggravated inflammatory RelA activity. Our investigation revealed frequent engagement of the noncanonical pathway in human IBD. In a mouse model of experimental colitis, we established that Nfkb2-mediated regulations escalated the RelA-driven proinflammatory gene response in intestinal epithelial cells, exacerbating the infiltration of inflammatory cells and colon pathologies. Our mechanistic studies clarified that cell-autonomous Nfkb2 signaling supplemented latent NF-κB dimers, leading to a hyperactive canonical RelA response in the inflamed colon. In sum, the regulation of latent NF-κB dimers appears to link noncanonical Nfkb2 signaling to RelA-driven inflammatory pathologies and may provide for therapeutic targets.

Early management of acute severe UC in the biologics era: development and international validation of a prognostic clinical index to predict steroid response.

OBJECTIVES: We aimed to determine whether changes in acute severe colitis (ASC) management have translated to improved outcomes and to develop a simple model predicting steroid non-response on admission. DESIGN: Outcomes of 131 adult ASC admissions (117 patients) in Oxford, UK between 2015 and 2019 were compared with data from 1992 to 1993. All patients received standard treatment with intravenous corticosteroids and endoscopic disease activity scoring (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)). Steroid non-response was defined as receiving medical rescue therapy or surgery. A predictive model developed in the Oxford cohort was validated in Australia and India (Gold Coast University Hospital 2015-2020, n=110; All India Institute of Medical Sciences, New Delhi 2018-2020, n=62). RESULTS: In the 2015-2019 Oxford cohort, 15% required colectomy during admission vs 29% in 1992-1993 (p=0.033), while 71 (54%) patients received medical rescue therapy (27% ciclosporin, 27% anti-tumour necrosis factor, compared with 27% ciclosporin in 1992-1993 (p=0.0015). Admission C reactive protein (CRP) (false discovery rate, p=0.00066), albumin (0.0066) and UCEIS scores (0.015) predicted steroid non-response. A four-point model was developed involving CRP of ≥100 mg/L (one point), albumin of ≤25 g/L (one point), and UCEIS score of ≥4 (1 point) or ≥7 (2 points). Patients scoring 0, 1, 2, 3 and 4 in the validation cohorts had steroid response rates of 100, 75.0%, 54.9%, 18.2% and 0%, respectively. Scoring of ≥3 was 84% (95% CI 0.70 to 0.98) predictive of steroid failure (OR 11.9, 95% CI 10.8 to 13.0). Colectomy rates in the validation cohorts were were 8%-11%. CONCLUSIONS: Emergency colectomy rates for ASC have halved in 25 years to 8%-15% worldwide. Patients who will not respond to corticosteroids are readily identified on admission and may be prioritised for early intensification of therapy.

Long-term Gastrointestinal Sequelae Following COVID-19: A Prospective Follow-up Cohort Study.

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) is associated with long-term gastrointestinal sequelae; however, prospective longitudinal data are sparse. We prospectively studied the frequency, spectrum, and risk factors of post infection functional gastrointestinal disorders/disorders of gut-brain interaction (PI-FGID/DGBI) after COVID-19. METHODS: Three hundred twenty cases with COVID-19 and 2 control groups, group A, 320 healthy spouses/family controls, and group B, 280 healthy COVID serology-negative controls, were prospectively followed up at 1, 3, and 6 months by using validated Rome IV criteria to evaluate the frequency of PI-FGID/DGBI. RESULTS: Of 320 cases, at 1 month 36 (11.3%) developed FGID symptoms. Persistent symptoms were noted in 27 (8.4%) at 3 months and in 21 (6.6%) at 6 months. At 3 months, 8 (2.5%) had irritable bowel syndrome, 7 (2.2%) had functional diarrhea, 6 (1.9%) had functional dyspepsia, 3 (0.9%) had functional constipation, 2 (0.6%) had functional dyspepsia-IBS overlap, and 1 (0.3%) had functional abdominal bloating/distention. Among symptomatic individuals at 3 months, 8 (29.6%) were positive for isolated carbohydrate malabsorption, 1 (3.7%) was positive for post infection malabsorption syndrome, and 1 (3.7%) was positive for intestinal methanogen overgrowth. None of the healthy controls developed FGID up to 6 months of follow-up (P < .01). Predictive factors at 3 and 6 months were severity of infection (P < .01) and presence of gastrointestinal symptoms at the time of infection (P < .01). CONCLUSIONS: COVID-19 led to significantly higher number of new onset PI-FGID/DGBI compared with healthy controls at 3 and 6 months of follow-up. If further investigated, some patients can be diagnosed with underlying malabsorption.

Revised Algorithmic Approach to Differentiate Between Nonspecific and Specific Etiologies of Chronic Terminal Ileitis.

INTRODUCTION: Chronic isolated terminal ileitis (TI) may be seen in Crohn's disease (CD) and intestinal tuberculosis (ITB) in addition to other etiologies that may be managed symptomatically. We developed a revised algorithm to distinguish patients with a specific etiology from a nonspecific etiology. METHODS: Patients with chronic isolated TI followed up from 2007 to 2022 were retrospectively reviewed. A specific (ITB or CD) diagnosis was made based on standardized criteria, and other relevant data were collected. Using this cohort, validation of a previously suggested algorithm was conducted. Furthermore, based on the results of a univariate analysis, a multivariate analysis with bootstrap validation was used to develop a revised algorithm. RESULTS: We included 153 patients (mean age 36.9 ± 14.6 years, males-70%, median duration-1.5 years, range: 0-20 years) with chronic isolated TI of whom 109 (71.2%) received a specific diagnosis (CD-69, ITB-40). On multivariate regression and validation statistics with a combination of clinical, laboratory, radiological, and colonoscopic findings, an optimism corrected c-statistic of 0.975 and 0.958 was obtained with and without histopathological findings, respectively. Revised algorithm, based on these, showed sensitivity, specificity, positive and negative predictive values, and overall accuracy of 98.2% (95% CI: 93.5-99.8), 75.0% (95% CI: 59.7-86.8), 90.7% (95% CI: 85.4-94.2), 94.3% (95% CI: 80.5-98.5) and 91.5%(95% CI:85.9-95.4), respectively. This was more sensitive and specific than the previous algorithm (accuracy 83.9%, sensitivity 95.5%, and specificity 54.6%). DISCUSSION: We developed a revised algorithm and a multimodality approach to stratify patients with chronic isolated TI into specific and nonspecific etiologies with an excellent diagnostic accuracy, which could potentially avoid missed diagnosis and unnecessary side effects of treatment.

Functional analysis of metalloenzymes from human gut microbiota and their role in ulcerative colitis.

AIM: Metalloenzymes produced by gut microbiota play an essential role in various physiological processes, and maintains homeostasis of gastrointestinal tract. Our study includes functional analysis of microbial metalloenzymes using metagenomics and metatranscriptomics data from Inflammatory Bowel Disease Multiomics Database. METHODS AND RESULTS: The distance matrix calculated by using metalloenzymes data produced significant results for bacterial taxonomy, with higher variance compared to HMP analysis in both Western and Indian population. Differential gene expression analysis revealed altered expression of ulcerative colitis (UC)-associated enzymes, increased folds changes in Prevotella and Megamonas transcripts; whereas, low transcripts of Alistipes genera. Further, docking and simulation studies performed on screened UC-associated enzymes revealed changes in catalytic efficiency and ligand interacting residues. CONCLUSION: The ß-diversity using microbes containing metalloenzymes suggests considering small group of specific genes or enzymes for understanding the diversity between UC and healthy individuals. The docking and differential gene expression analysis collectively indicate the probable role of metalloenzymes and few UC-associated enzymes in the severity of UC.

Disorders of gut-brain interaction in post-acute COVID-19 syndrome.

The novel coronavirus SARS-CoV-2 is responsible for the devastating pandemic which has caused more than 5 million deaths across the world until today. Apart from causing acute respiratory illness and multiorgan dysfunction, there can be long-term multiorgan sequalae after recovery, which is termed 'long COVID-19' or 'post-acute COVID-19 syndrome'. Little is known about long-term gastrointestinal (GI) consequences, occurrence of post-infection functional gastrointestinal disorders and impact the virus may have on overall intestinal health. In this review, we put forth the various mechanisms which may lead to this entity and possible ways to diagnose and manage this disorder. Hence, making physicians aware of this spectrum of disease is of utmost importance in the present pandemic and this review will help clinicians understand and suspect the occurrence of functional GI disease post recovery from COVID-19 and manage it accordingly, avoiding unnecessary misconceptions and delay in treatment.

Faecal microbiota transplantation with anti-inflammatory diet (FMT-AID) followed by anti-inflammatory diet alone is effective in inducing and maintaining remission over 1 year in mild to moderate ulcerative colitis: a randomised controlled trial.

OBJECTIVE: Microbiome and dietary manipulation therapies are being explored for treating ulcerative colitis (UC). We aimed to examine the efficacy of multidonor faecal microbiota transplantation (FMT) and anti-inflammatory diet in inducing remission followed by long-term maintenance with anti-inflammatory diet in patients with mild-moderate UC. DESIGN: This open-labelled randomised controlled trial (RCT) randomised patients with mild-moderate (Simple Clinical Colitis Activity Index (SCCAI) 3-9) endoscopically active UC (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)>1) on stable baseline medications in 1:1 ratio to FMT and anti-inflammatory diet (FMT-AID) versus optimised standard medical therapy (SMT). The FMT-AID arm received seven weekly colonoscopic infusions of freshly prepared FMT from multiple rural donors(weeks 0-6) with anti-inflammatory diet. Baseline medications were optimised in the SMT arm. Clinical responders (decline in SCCAI>3) at 8 weeks in both arms were followed until 48 weeks on baseline medications (with anti-inflammatory diet in the FMT-AID arm). Primary outcome measures were clinical response and deep remission (clinical-SCCAI <2; and endoscopic-UCEIS <1) at 8 weeks, and deep remission and steroid-free clinical remission at 48 weeks. RESULTS: Of the 113 patients screened, 73 were randomised, and 66 were included in (35-FMT-AID; 31-SMT) modified intention-to-treat analysis (age-35.7±11.1 years; male-60.1%; disease duration-48 (IQR 24-84) months; pancolitis-34.8%; SCCAI-6 (IQR 5-7); UCEIS-4 (IQR 3-5)). Baseline characteristics were comparable. FMT-AID was superior to SMT in inducing clinical response (23/35 (65.7%) vs 11/31 (35.5%), p=0.01, OR 3.5 (95% CI 1.3 to 9.6)), remission (21/35 (60%) vs 10/31 (32.3%), p=0.02, OR 3.2 (95% CI 1.1 to 8.7)) and deep remission (12/33 (36.4%) vs 2/23 (8.7%), p=0.03, OR 6.0 (95% CI 1.2 to 30.2)) at 8 weeks. Anti-inflammatory diet was superior to SMT in maintaining deep remission until 48 weeks (6/24 (25%) vs 0/27, p=0.007). CONCLUSION: Multidonor FMT with anti-inflammatory diet effectively induced deep remission in mild-moderate UC which was sustained with anti-inflammatory diet over 1 year. TRIAL REGISTRATION NUMBER: ISRCTN15475780.

Considerations when starting patients on multiple biologics and small molecules.

PURPOSE OF REVIEW: Inflammatory bowel disease (IBD) is complex disease that poses significant economic, and psychological burden on patients. Despite advent of newer biologics and small molecules targeting different aspects of immunopathogenesis, there appears to be a plateau in clinical outcomes. In this review we discuss the role of multiple biologics, existing evidence and various considerations when prescribing multiple biologics. RECENT FINDINGS: Recent scientific advances helped to unravel the pathophysiology of inflammatory bowel disease and newer cytokines have been identified which can be potential targets in the management of IBD. Targeting more than one cytokine appears to be logical solution to break the therapeutic ceiling to improve clinical outcomes in IBD. The combination biologics appear safe and effective; however, the available evidence is limited. Refractory IBD, presence of other immune mediated inflammatory diseases and extra intestinal manifestations are currently the common considerations of combination biologics in IBD. SUMMARY: Inflammatory bowel disease is a complex immune mediated disease with diverse clinical presentation and often has a complicated clinical course requiring multidisciplinary management. As the number of targeted therapies increases so does the concern on their safety and efficacy. Combination biologics though may appear to be safe, we need well designed prospective studies for firm conclusions.

Relapse rates after withdrawal of thiopurines in patients with inflammatory bowel disease.

PURPOSE: Withdrawal of thiopurines after remission is associated with an increased risk of relapse in patients with inflammatory bowel disease (IBD). However, long-term data on thiopurine withdrawal is limited, especially from developing countries where the cost of long-term therapy poses a significant burden on patients. METHODS: Patients with IBD on thiopurine monotherapy for ≥ 4 months, who stopped thiopurines while in clinical remission and were not on any other immunomodulator or biologics at the time of withdrawal, were included in this retrospective analysis. RESULTS: Among 1093 patients with IBD on thiopurine monotherapy, 461 patients stopped thiopurine due to various reasons. Among these, 218 (ulcerative colitis (UC) = 179; Crohn's disease (CD) = 39) patients were in clinical remission and were continued on mesalamine. Overall, 36.7% (n = 80) relapsed after a median duration of 20 months (IQR: 9-49). Relapse rate was higher in UC than CD (39.7% vs 23%, p = 0.055). Cumulative probabilities of relapse were 17%, 34%, and 44% at the end of 1, 3, and 5 years, respectively. The relapse rate at 5 years was significantly lower in patients who had stopped azathioprine after 4 years of therapy (31% vs 54%, p = 0.007). On multi-variate cox regression analysis, male sex [HR: 1.6(1.0-2.6), p = 0.02] and short duration of therapy with thiopurines [HR: 1.02 (1.01-1.02), p = 0.004] before withdrawal were associated with increased risk of relapse. CONCLUSION: Approximately 50% patients with IBD in remission would relapse after 5 years of thiopurine withdrawal. Male sex and shorter treatment duration predict relapse. Treatment should be continued in patients who tolerate and maintain remission on long-term thiopurine.

Minimal risk of lymphoma and non-melanoma skin cancer despite long-term use of thiopurines in patients with inflammatory bowel disease: A longitudinal cohort analysis from northern India.

BACKGROUND AND AIM: Thiopurines are widely used to maintain remission in both ulcerative colitis (UC) and Crohn's disease (CD). Reported effectiveness and tolerability rates have been variable across studies. There are only sparse data in Asian population regarding the long-term efficacy and safety of thiopurines. METHODS: Records of 5351 patients followed up at inflammatory bowel disease (IBD) clinic, All India Institute of Medical Sciences, New Delhi from 2004 to 2020 were evaluated retrospectively. Safety was evaluated in terms of long-term adverse events and development of malignancy. RESULTS: Of 5351 patients with IBD, 1093 who received thiopurine for > 3 months (UC = 788 [proctitis-1.9%, left-sided colitis-44.9%, & pancolitis-53.1%] & CD = 305 [inflammatory-42.6%, stricturing-46.9%, & fistulizing-10.5%]) were included (60.8%-male patients). Follow up and treatment duration on thiopurine were 7 (4-12) years and 39.4 ± 40.3 months, respectively, with 254 (23.2%) patients receiving thiopurines for more than 5 and 68 (6.2%) receiving for more than 10 years. Three hundred and fifty-nine (UC: 249 [31.6%]; CD: 110 [36.1%]; P = 0.1) patients developed adverse events; commonest was myelosuppression (23.4%) followed by gastrointestinal intolerance (3%), flu-like illness (1.7%), and arthralgia/myalgia (1.4%). Myelosuppression was the commonest cause of thiopurine withdrawal. No patient (including 254 patients on thiopurine for ≥ 5 years) developed lymphoma or non-melanoma skin cancer. The cumulative probability of staying free from adverse events in overall IBD cohort at 1, 2, and 5 years was 78.6%, 71.9%, and 68.4%, respectively, and this was comparable between UC and CD (P = 0.09). CONCLUSION: Long-term follow up of patients with IBD from northern India on thiopurine monotherapy demonstrated minimal risk of development of lymphoma as well as non-melanoma skin cancer.

Role of a probiotic strain in the modulation of gut microbiota and cytokines in inflammatory bowel disease.

OBJECTIVE: To assess the effect of a probiotic strain Bacillus clausii UBBC-07 on gut microbiota and cytokines in IBD patients. METHOD: Patients were randomly allocated to either placebo or probiotic Bacillus clausii UBBC-07 for four weeks along with the standard medical treatment (SMT). Enrolled patients were evaluated before and after intervention for presence of the given probiotic, change in gut microbiota, change in serum cytokines, serotonin and dopamine, symptoms of disease, physical, behavioral and psychological parameters. RESULTS: Probiotic strain Bacillus clausii UBBC-07 showed good survival in IBD patients in the treatment group (p < 0.01) without any reported adverse event. Metagenomic analysis showed that the given probiotic strain was able to modulate the gut microbiota in treated group. Phylum Firmicutes was increased and phylum Bacteroidetes was decreased in the probiotic treated group. A significant increase was observed in the abundance of anaerobic bacterial genera Lactobacillus, Bifidobacterium and Faecalibacterium in the probiotic treated group (p < 0.01) as compared to placebo group. Significant increase was observed in IL-10 (p < 0.05) and variable decrease in the secretion of IL-1ß, TNF- α, IL-6, IL -17 and IL -23 in probiotic treated group. In the treatment group a significant decrease in the symptoms of IBD and improvement in the psychological parameter to various degrees was noted. CONCLUSION: These results indicated that probiotic strain B clausii UBBC-07 affected the gut microbiota and cytokine secretion and shown efficacy in IBD patients.

Long-Term Outcomes of Endovascular Interventions in More than 500 patients with Budd-Chiari Syndrome.

PURPOSE: To assess and compare the long-term outcomes of various endovascular interventions in patients with Budd-Chiari syndrome (BCS). MATERIALS AND METHODS: In this single-center retrospective study, 510 consecutive patients with BCS who had undergone a total of 618 endovascular procedures from January 2001 to December 2019 were included. Details of the type of endovascular intervention, technical success, clinical success, patency rate, complications, and survival outcomes were analyzed. RESULTS: The overall technical success rate was 96% (593 of 618 procedures; 500 in treatment-naïve patients and 93 repeat interventions for recurrent disease). Endovascular procedures included recanalization procedures (angioplasty and stent placement) in 355 patients (71%) and transjugular intrahepatic portosystemic shunt (TIPS) creation in 145 (29%). Major postprocedure complications occurred in 14 patients (2.8%). Vascular/stent restenosis occurred in 95 patients (19%), and successful repeat intervention was performed in 82 of those 95 (86.3%). An additional 11 of these 82 (13.4%) underwent a third intervention for restenosis. In the recanalization and TIPS groups, the 1- and 5-y cumulative patency rates were 87% and 74% and 95% and 68%, respectively. The 1- and 5-y survival rates were 96% and 89% and 90% and 76%, respectively. CONCLUSIONS: Endovascular interventions for BCS are feasible and safe in the majority of patients, with excellent short- and long-term patency and survival rates.

Gut microbiome diversity in acute severe colitis is distinct from mild to moderate ulcerative colitis.

BACKGROUND AND AIM: Although the gut microbiome of patients with ulcerative colitis (UC) has been characterized, no study has characterized the gut microbiome in acute severe colitis (ASC). We compared the gut microbiome of patients with UC, ASC, and healthy controls (HCs). METHODS: Patients with mild to moderate UC (n = 24), ASC (n = 19 with 21 episodes) and HCs (n = 50) were recruited prospectively. A 16SrDNA amplicon approach was used to explore gut microbial diversity and taxonomic repertoires. UC was diagnosed using European Crohn's and Colitis Organization guidelines, and ASC was diagnosed using Truelove and Witts' criteria. RESULTS: The normalized alpha diversity was significantly lower in ASC than mild-moderately active UC (P < 0.05) or HC (P < 0.001). The gut microbiome in ASC was highly unstable, as characterized by high intracohort variation (analyzed using J-divergence measure), which was significantly greater than in UC or HC. On principal coordinate analysis, the microbiome of HC and UC were similar, with the ASC cohort being distinct from both. Comparison of ranked abundances identified four distinct clusters of genera (G1, G2, G3, and G4), with specific trends in their abundance across three groups: G1/G2A clusters had the least, whereas G3 had the highest abundance in the ASC cohort. CONCLUSIONS: Gut microbial diversity is lower in ASC than mild-moderate UC or HCs. Gut microbiome composition is increasingly unstable in ASC, with a distinct abundance of specific genera varying between HCs and ASC. Mild-moderate UC lies within the spectrum.

Risk of Tuberculosis in Patients With Inflammatory Bowel Disease on Infliximab or Adalimumab Is Dependent on the Local Disease Burden of Tuberculosis: A Systematic Review and Meta-Analysis.

OBJECTIVES: Infliximab (IFX) or adalimumab (ADA) use in patients with inflammatory bowel disease (IBD) leads to increased risk of tuberculosis (TB). This meta-analysis evaluated the factors which determine this risk, with special focus on local TB incidence. METHODS: All studies until January 31, 2019, which reported the development of TB in patients with IBD on IFX/ADA, were included after searching PubMed and Embase. Data regarding disease type, number of patients on IFX/ADA, number of patients who developed TB, mean age at IFX/ADA initiation, median duration of development of TB, and latent TB (LTB) were extracted. The details on local TB incidence were obtained from the World Health Organization database, and the studies were stratified into low (<10/100,000), intermediate (10-40/100,000), and high TB burden countries (>40/100,000). Random effect meta-analysis was performed to calculate the overall pooled prevalence and prevalence based on local TB burden. RESULTS: Of 130,114 patients (128 studies), 373 developed TB (pooled prevalence: 0.08% [95% confidence interval {CI}: 0.05%-0.10%]). The risk increased with increasing TB burden, pooled prevalence being 0.02% (95% CI: 0.02%-0.03%), 0.21% (95% CI: -0.02% to 0.43%), and 1.59% (95% CI: 1.19%-2.00%) for low, intermediate, and high TB burden countries, respectively. Seventy-three percent of patients who developed TB had no evidence of LTB on screening, the proportion being independent of TB burden. There was no effect of disease or treatment type, study type, gender, age at IFX/ADA initiation, and follow-up duration on TB prevalence. DISCUSSION: TB risk in patients with IBD on IFX/ADA depends on the local TB burden and is independent of disease/treatment type.