Comparison of Vonoprazan vs Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial.

BACKGROUND & AIMS: High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aimed to compare the efficacy of vonoprazan vs PPI for preventing high-risk PU rebleeding after hemostasis. METHODS: A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20 mg twice a day for 3 days, then 20 mg once a day for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/h for 3 days, then omeprazole 20 mg twice a day for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3- and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety. RESULTS: Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable between the 2 groups. The 30-day rebleeding rates in vonoprazan and PPI groups were 7.1% (7 of 98) and 10.4% (10 of 96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference, -3.3; 95% confidence interval, -11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates in the vonoprazan group remained noninferior to PPI (P < .001 by Farrington and Manning test). All secondary outcomes were also comparable between the 2 groups. CONCLUSION: In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI. (ClinicalTrials.gov, Number: NCT05005910).

Joint Asian Pacific Association of Gastroenterology (APAGE)-Asian Pacific Society of Digestive Endoscopy (APSDE) clinical practice guidelines on the use of non-invasive biomarkers for diagnosis of colorectal neoplasia.

Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE-APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.

Global Hospitalization Trends for Crohn's Disease and Ulcerative Colitis in the 21st Century: A Systematic Review With Temporal Analyses.

BACKGROUND & AIMS: The evolving epidemiologic patterns of inflammatory bowel disease (IBD) throughout the world, in conjunction with advances in therapeutic treatments, may influence hospitalization rates of IBD. We performed a systematic review with temporal analysis of hospitalization rates for IBD across the world in the 21st century. METHODS: We systematically reviewed Medline and Embase for population-based studies reporting hospitalization rates for IBD, Crohn's disease (CD), or ulcerative colitis (UC) in the 21st century. Log-linear models were used to calculate the average annual percentage change (AAPC) with associated 95% confidence intervals (95% CIs). Random-effects meta-analysis pooled country-level AAPCs. Data were stratified by the epidemiologic stage of a region: compounding prevalence (stage 3) in North America, Western Europe, and Oceania vs acceleration of incidence (stage 2) in Asia, Eastern Europe, and Latin America vs emergence (stage 1) in developing countries. RESULTS: Hospitalization rates for a primary diagnosis of IBD were stable in countries in stage 3 (AAPC, -0.13%; 95% CI, -0.72 to 0.97), CD (AAPC, 0.20%; 95% CI, -1.78 to 2.17), and UC (AAPC, 0.02%; 95% CI, -0.91 to 0.94). In contrast, hospitalization rates for a primary diagnosis were increasing in countries in stage 2 for IBD (AAPC, 4.44%; 95% CI, 2.75 to 6.14), CD (AAPC, 8.34%; 95% CI, 4.38 to 12.29), and UC (AAPC, 3.90; 95% CI, 1.29 to 6.52). No population-based studies were available for developing regions in stage 1 (emergence). CONCLUSIONS: Hospitalization rates for IBD are stabilizing in countries in stage 3, whereas newly industrialized countries in stage 2 have rapidly increasing hospitalization rates, contributing to an increasing burden on global health care systems.

Development of the global inflammatory bowel disease visualization of epidemiology studies in the 21st century (GIVES-21).

BACKGROUND: There is a rapid increase in the incidence of inflammatory bowel diseases (IBD) in newly industrialized countries, yet epidemiological data is incomplete. We herein report the methodology adopted to study the incidence of IBD in newly industrialized countries and to evaluate the effect of environmental factors including diet on IBD development. METHODS: Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) is a population-based cohort of newly diagnosed persons with Crohn's disease and ulcerative colitis in Asia, Africa, and Latin America to be followed prospectively for 12 months. New cases were ascertained from multiple sources and were entered into a secured online system. Cases were confirmed using standard diagnostic criteria. In addition, endoscopy, pathology and pharmacy records from each local site were searched to ensure completeness of case capture. Validated environmental and dietary questionnaires were used to determine exposure in incident cases prior to diagnosis. RESULTS: Through November 2022, 106 hospitals from 24 regions (16 Asia; 6 Latin America; 2 Africa) have joined the GIVES-21 Consortium. To date, over 290 incident cases have been reported. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, medication history and environmental and dietary exposures data collected. We have established a comprehensive platform and infrastructure required to examine disease incidence, risk factors and disease course of IBD in the real-world setting. CONCLUSIONS: The GIVES-21 consortium offers a unique opportunity to investigate the epidemiology of IBD and explores new clinical research questions on the association between environmental and dietary factors and IBD development in newly industrialized countries.

Emerging inflammatory bowel disease demographics, phenotype, and treatment in South Asia, South-East Asia, and Middle East: Preliminary findings from the Inflammatory Bowel Disease-Emerging Nations' Consortium.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South-East Asia, and the Middle East, yet epidemiological data are scarce. METHODS: We performed a cross-sectional study of IBD demographics, disease phenotype, and treatment across 38 centers in 15 countries of South Asia, South-East Asia, and Middle East. Intergroup comparisons included gross national income (GNI) per capita. RESULTS: Among 10 400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD unclassified 227, and 58% male). Peak age of onset was in the third decade, with a low proportion of elderly-onset IBD (5% age > 60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was the commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12 months; interquartile range 5-30). Treatment of CD included mesalamine, steroids, and immunomodulators (61%, 51%, and 56%, respectively), but a fifth received empirical antitubercular therapy. Treatment with biologics was uncommon (4% UC and 13% CD), which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD) per 100 patients per year. CONCLUSIONS: The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population based. UC is twice as common as CD, familial disease is uncommon, and rates of surgery are low. Biologic use correlates with per capita GNI.

Continuous Infusion of Fluid Hydration Over 24 Hours Does Not Prevent Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

BACKGROUND: Aggressive intravenous fluid hydration, by administering 3500 mL of lactated Ringer's solution (LRS) in 9 h with a peri-procedural bolus, reduces post-ERCP pancreatitis (PEP) incidence. A concern of this strategy is adverse events related to volume overload; however, the impact of fluid hydration over an extended period without a bolus on PEP is unknown. AIM: To assess the effect of continuous infusion of high-volume fluid at a constant rate over 24 h on PEP incidence and severity. METHODS: Two-hundred patients were randomly assigned (1:1) to receive either 3600 mL of LRS in 24 h starting 2 h before the ERCP (high-volume group) or maintenance fluid hydration calculated by the Holliday-Segar method (control group). RESULTS: The mean age of the patients was 50.6 ± 11.6 years. The predominant indications were choledocholithiasis (48%) and malignancies (32%). Patient demographics and PEP risk factors were similar in both groups. Patients in the high-volume group received significantly more fluid than the control group (3600 vs. 2413 ml, P < 0.001). PEP incidence was not different between the high-volume and the control group (14% vs. 15%; relative risk 0.93: 95% CI 0.48-1.83, P = 0.84). There were no differences in moderate to severe PEP (3% vs. 4%; relative risk 0.75: 95% CI, 0.17-3.27, P = 1.00). Subgroup analysis did not show a benefit in high-risk patients. Only one patient in the control group developed peripheral edema. CONCLUSIONS: An infusion of high-volume hydration over 24 h is not sufficient to provide optimal hydration for PEP prevention. CLINICAL TRIAL REGISTRY NUMBER: No. NCT02821546.

Diagnostic yield of esophagogastroduodenoscopy, colonoscopy, and small bowel endoscopy in Thai adults with chronic diarrhea.

BACKGROUND: Gastrointestinal endoscopy is frequently recommended for chronic diarrhea assessment in Western countries, but its benefit in the Southeast Asia region is not well established. METHODS: Medical records of consecutive patients undergoing esophagogastroduodenoscopy (EGD), colonoscopy, and small bowel endoscopy for chronic diarrhea from 2008 to 2018 were reviewed. Small bowel endoscopy included push enteroscopy, balloon-assisted enteroscopy (BAE), and video capsule endoscopy (VCE). The diagnostic yield of each endoscopic modality and predictors for positive small bowel endoscopy were analyzed. RESULTS: A total of 550 patients were included. The mean age was 54 years, and 266 (46.3%) patients were male. The mean hemoglobin and albumin levels were 11.6 g/dL and 3.6 g/dL, respectively. EGD and colonoscopy were performed in 302 and 547 patients, respectively, and the diagnostic yield was 24/302 (7.9%) for EGD and 219/547 (40.0%) for colonoscopy. EGD did not reveal positive findings in any patients with normal colonoscopy. Fifty-one patients with normal EGD and colonoscopy underwent small bowel endoscopy. Push enteroscopy, BAE, and VCE were performed in 28, 21, and 19 patients with a diagnostic yield of 5/28 (17.9%), 14/21 (66.7%), and 8/19 (42.1%), respectively. Significant weight loss, edema, and hypoalbuminemia were independent predictors for the positive yield of small bowel endoscopy. CONCLUSION: Colonoscopy was an essential diagnostic tool in identifying the cause of chronic diarrhea in Thai patients, whereas EGD provided some benefits. Small bowel endoscopy should be performed when colonoscopy and EGD were negative, particularly in patients with significant weight loss, edema, and hypoalbuminemia.

Patient characteristics, clinical manifestations, prognosis, and factors associated with gastrointestinal cytomegalovirus infection in immunocompetent patients.

BACKGROUND: Gastrointestinal (GI) cytomegaloviral (CMV) infection is common among patients with immunocompromised status; however, data specific to GI-CMV infection in immunocompetent patients are comparatively limited. METHODS: This retrospective study included patients diagnosed with GI-CMV infection at Siriraj Hospital (Bangkok, Thailand) during 2008-2017. Baseline characteristics, presentations, comorbid conditions, endoscopic findings, treatments, and outcomes were compared between immunocompetent and immunocompromised. RESULTS: One hundred and seventy-three patients (56 immunocompetent, 117 immunocompromised) were included. Immunocompetent patients were significantly older than immunocompromised patients (73 vs. 48.6 years, p < 0.0001). Significantly more immunocompetent patients were in the ICU at the time of diagnosis (21.0% vs. 8.6%, p = 0.024). GI bleeding was the leading presentation in immunocompetent, while diarrhea and abdominal pain were more common in immunocompromised. Blood CMV viral load was negative in significantly more immunocompetent than immunocompromised (40.7% vs. 12.9%, p = 0.002). Ganciclovir was the main treatment in both groups. Significantly more immunocompetent than immunocompromised did not receive any specific therapy (25.5% vs. 4.4%, p ≤ 0.01). Six-month mortality was significantly higher among immunocompetent patients (39.0% vs. 22.0%, p = 0.047). Independent predictors of death were old age and inpatient or ICU clinical setting. Treatment with antiviral agents was the only independent protective factor. CONCLUSION: GI-CMV infection was frequently observed among immunocompetent elderly patients with comorbidities or severe concomitant illnesses. GI bleeding was the most common presentation. Blood CMV viral load was not diagnostically helpful. Significantly higher mortality was observed in immunocompetent than in immunocompromised patients, but this could be due to more severe concomitant illnesses in the immunocompetent group.

Prevalence and Effect of Intestinal Infections Detected by a PCR-Based Stool Test in Patients with Inflammatory Bowel Disease.

BACKGROUND: The advent of PCR-based stool testing has identified a greatly increased number of infectious agents in IBD, but their clinical significance is unknown. AIMS: To determine the infectious agent prevalence and the clinical significance of these infectious agents in IBD patients. METHODS: This cross-sectional study compared the prevalence of GI infections among IBD patients with active and quiescent disease versus healthy controls. Among actively inflamed patients, we compared clinical characteristics, medication use, and disease course between those with positive and negative tests. RESULTS: Three hundred and thirty-three IBD patients and 52 healthy volunteers were included. The IBD group was divided into active Crohn's disease (CD, n = 113), inactive CD (n = 53), active ulcerative colitis (UC, n = 128), and inactive UC (n = 39). A significantly higher percentage of actively inflamed patients had positive stool tests (31.1%) compared to those with quiescent disease (7.6%, P = < 0.001) and healthy controls (13.5%, P = 0.01). In actively inflamed patients, shorter symptom duration and the use of multiple immunosuppressive agents were significantly associated with positive stool tests. Escalation of immunosuppressive therapy was less frequent in those with positive (61.3%) than with negative tests (77.7%, P = < 0.01). However, the need for surgery (13.3% vs. 18.7%, respectively, P = 0.31) and hospitalization (14.7% vs. 17.5%, respectively, P = 0.57) in 90 days was not significantly different. CONCLUSION: GI infections are common in IBD patients with active disease. Evaluating patients for infection may help avoid unnecessary escalation of immunosuppressants, especially during an acute flare or combination immunosuppression.

Population Density and Risk of Inflammatory Bowel Disease: A Prospective Population-Based Study in 13 Countries or Regions in Asia-Pacific.

INTRODUCTION: Living in an urban environment may increase the risk of developing inflammatory bowel disease (IBD). It is unclear if this observation is seen globally. We conducted a population-based study to assess the relationship between urbanization and incidence of IBD in the Asia-Pacific region. METHODS: Newly diagnosed IBD cases between 2011 and 2013 from 13 countries or regions in Asia-Pacific were included. Incidence was calculated with 95% confidence interval (CI) and pooled using random-effects model. Meta-regression analysis was used to assess incidence rates and their association with population density, latitude, and longitude. RESULTS: We identified 1175 ulcerative colitis (UC), 656 Crohn's disease (CD), and 37 IBD undetermined (IBD-U). Mean annual IBD incidence per 100 000 was 1.50 (95% CI: 1.43-1.57). India (9.31; 95% CI: 8.38-10.31) and China (3.64; 95% CI, 2.97-4.42) had the highest IBD incidence in Asia. Incidence of overall IBD (incidence rate ratio [IRR]: 2.19; 95% CI: 1.01-4.76]) and CD (IRR: 3.28; 95% CI: 1.83-9.12) was higher across 19 areas of Asia with a higher population density. In China, incidence of IBD (IRR: 2.37; 95% CI: 1.10-5.16) and UC (IRR: 2.63; 95% CI: 1.2-5.8) was positively associated with gross domestic product. A south-to-north disease gradient (IRR: 0.94; 95% CI: 0.91-0.98) was observed for IBD incidence and a west-to-east gradient (IRR: 1.14; 95% CI: 1.05-1.24) was observed for CD incidence in China. This study received IRB approval. CONCLUSIONS: Regions in Asia with a high population density had a higher CD and UC incidence. Coastal areas within China had higher IBD incidence. With increasing urbanization and a shift from rural areas to cities, disease incidence may continue to climb in Asia.

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia.

The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.

Efficacy and safety of nortriptyline in functional dyspepsia in Asians: A randomized double-blind placebo-controlled trial.

BACKGROUND AND AIM: Current treatments of functional dyspepsia (FD) are unsatisfied. Tricyclic antidepressants alter visceral hypersensitivity and brain-gut interaction. We assessed the efficacy and safety of nortriptyline in patients with FD. METHODS: Patients diagnosed with FD according to Rome III criteria who failed to respond to proton pump inhibitor and prokinetic treatment were randomly assigned to either once daily 10-mg nortriptyline or placebo. The primary endpoint was the rate of responders defined as > 50% reduction in dyspepsia symptom score after 8 weeks of treatment. The secondary endpoints were improvement in quality of life as assessed by 36-Item Short Form Health Survey score and safety. RESULTS: Sixty-one patients (nortriptyline 28 and placebo 33) were enrolled. Dyspepsia symptom score and duration of symptoms were balanced at entry between both groups. Eight and seven patients in nortriptyline and placebo groups were lost to follow up. Seven patients withdrew due to mild adverse events (nortriptyline 1 and placebo 6). Overall, 19 with nortriptyline and 20 with placebo completed the study. Patients receiving nortriptyline did not achieve higher response rate than those in placebo in both intention-to-treat (53.6% vs 57.6%, P = 0.75) and per-protocol (76.5% vs 73.7%, P = 1.00) analyses. Nortriptyline did not provide improvement in quality of life. The mean difference was 3.8 (P = 0.36) and 0.88 (P = 0.86) by intention-to-treat and 2.9 (P = 0.57) and 3.5 (P = 0.57) by per-protocol analyses in physical and mental component, respectively. All adverse events were minor and similar in both groups. CONCLUSION: Nortriptyline was not superior to placebo in management of patients with FD.

Systemic Inflammatory Responses in Ulcerative Colitis Patients and Clostridium difficile Infection.

BACKGROUND/AIMS: Finding differences in systemic inflammatory response in ulcerative colitis (UC), UC with Clostridium difficile infection (CDI), and CDI could lead to a better ability to differentiate between UC with symptomatic CDI and UC with C. difficile colonization, and could identify specific inflammatory pathways for UC or CDI, which could be therapeutic targets. METHODS: We prospectively collected sera from symptomatic UC patients whose stools were tested for toxigenic C. difficile, and from CDI patients who did not have UC (CDI-noUC). The UC patients with positive tests (UC-CDI) were further categorized into responders to CDI treatment (UC-CDI-R) and non-responders (UC-CDI-NR). We compared serum inflammatory mediators among groups using unadjusted and adjusted multivariable statistics. RESULTS: We included 117 UC [27 UC-CDI, 90 UC without CDI (UC-noCDI)] and 16 CDI-noUC patients. Principal component analysis (PCA) did not reveal significant differences either between UC-CDI and UC-noCDI groups, or between UC-CDI-R and UC-CDI-NR groups. In contrast, the PCA showed significant separation between the UC and CDI-noUC groups (P = 0.002). In these two groups, hepatocyte growth factor (HGF) and chemokine (C-C motif) ligand 2 (CCL2) levels were significantly lower and IL-23 levels were higher in UC patients in multivariable analyses. The model to distinguish UC from CDI including IL-23, HGF, CCL2, age, gender, and HGB had an AuROC of 0.93. CONCLUSION: Inflammatory profiles could not distinguish UC-CDI from UC-noCDI, and UC-CDI-R from UC-CDI-NR. However, the UC and CDI-noUC groups were significantly different. Future work should examine whether therapeutic agents inhibiting IL-23 or stimulating HGF can treat UC.

Factors That Predict High Health Care Utilization and Costs for Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: A subset of patients with inflammatory bowel diseases (IBD) have continuously active inflammation, leading to a high number of complications and high direct health care costs (diagnostic tests, medications, and surgeries) and indirect costs (reduced employment and productivity and fewer opportunities for activities). Identifying these high-risk patients and providing effective interventions could produce better outcomes and reduce costs. We used prior year data to create IBD risk models to predict IBD-related hospitalizations, emergency department visits, and high treatment charges (>$30,000/year) in the subsequent year. METHODS: We performed a retrospective study of medical records from all patients with IBD treated at the University of Michigan Hospital from fiscal years 2013-2015. We selected clinical variables from the prior year and tested their abilities to predict 3 adverse outcomes (IBD-related hospitalizations, emergency department visits, and treatment charges >$30,000/year) in the subsequent year. Individual patients were only included once in the data set. We created a multivariate model that was based on a 70% randomly selected cohort (1005 patients) and validated the model on the other 30% (425 patients). Logistic regression was used for bivariate and multivariate analyses. RESULTS: Factors that predicted high-cost outcomes included the presence of psychiatric illness, use of corticosteroids, use of narcotics, low levels of hemoglobin, and high numbers of IBD-related hospitalizations. In the validation cohort, the model predicted IBD-related hospitalizations, emergency department visits, and high charges in the following year with receiver operating characteristic curve values of 0.751, 0.738, and 0.744, respectively. CONCLUSIONS: We identified 5 factors that can effectively identify patients with IBD at high risk for hospitalization, emergency department visits, and high treatment charges in the next year. These patients should be closely monitored and aggressively managed.

Early Course of Inflammatory Bowel Disease in a Population-Based Inception Cohort Study From 8 Countries in Asia and Australia.

BACKGROUND & AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Asia, but little is known about disease progression in this region. The Asia-Pacific Crohn's and Colitis Epidemiology Study was initiated in 2011, enrolling subjects from 8 countries in Asia (China, Hong Kong, Indonesia, Sri Lanka, Macau, Malaysia, Singapore, and Thailand) and Australia. We present data from this ongoing study. METHODS: We collected data on 413 patients diagnosed with IBD (222 with ulcerative colitis [UC], 181 with Crohn's disease [CD], 10 with IBD unclassified; median age, 37 y) from 2011 through 2013. We analyzed the disease course and severity and mortality. Risks for medical and surgical therapies were assessed using Kaplan-Meier analysis. RESULTS: The cumulative probability that CD would change from inflammatory to stricturing or penetrating disease was 19.6%. The cumulative probabilities for use of immunosuppressants or anti-tumor necrosis factor agents were 58.9% and 12.0% for patients with CD, and 12.7% and 0.9% for patients with UC, respectively. Perianal CD was associated with an increased risk of anti-tumor necrosis factor therapy within 1 year of its diagnosis (hazard ratio, 2.97; 95% confidence interval, 1.09-8.09). The cumulative probabilities for surgery 1 year after diagnosis were 9.1% for patients with CD and 0.9% for patients with UC. Patients with CD and penetrating disease had a 7-fold increase for risk of surgery, compared with patients with inflammatory disease (hazard ratio, 7.67; 95% confidence interval, 3.93-14.96). The overall mortality for patients with IBD was 0.7%. CONCLUSIONS: In a prospective population-based study, we found that the early course of disease in patients with IBD in Asia was comparable with that of the West. Patients with CD frequently progress to complicated disease and have accelerated use of immunosuppressants. Few patients with early stage UC undergo surgery in Asia. Increasing our understanding of IBD progression in different populations can help optimize therapy and improve outcomes.

Meta-Analytic Bayesian Model For Differentiating Intestinal Tuberculosis from Crohn's Disease.

OBJECTIVES: Distinguishing intestinal tuberculosis (ITB) from Crohn's disease (CD) is difficult, although studies have reported clinical, endoscopic, imaging, and laboratory findings that help to differentiate these two diseases. We aimed to produce estimates of the predictive power of these findings and construct a comprehensive model to predict the probability of ITB vs. CD. METHODS: A systematic literature search for studies differentiating ITB from CD was conducted in MEDLINE, PUBMED, and EMBASE from inception until September 2015. Fifty-five distinct meta-analyses were performed to estimate the odds ratio of each predictive finding. Estimates with a significant difference between CD and ITB and low to moderate heterogeneity (I2<50%) were incorporated into a Bayesian prediction model incorporating the local pretest probability. RESULTS: Thirty-eight studies comprising 2,117 CD and 1,589 ITB patients were included in the analyses. Findings in the model that significantly favored CD included male gender, hematochezia, perianal disease, intestinal obstruction, and extraintestinal manifestations; endoscopic findings of longitudinal ulcers, cobblestone appearance, luminal stricture, mucosal bridge, and rectal involvement; pathological findings of focally enhanced colitis; and computed tomographic enterography (CTE) findings of asymmetrical wall thickening, intestinal wall stratification, comb sign, and fibrofatty proliferation. Findings that significantly favored ITB included fever, night sweats, lung involvement, and ascites; endoscopic findings of transverse ulcers, patulous ileocecal valve, and cecal involvement; pathological findings of confluent or submucosal granulomas, lymphocyte cuffing, and ulcers lined by histiocytes; a CTE finding of short segmental involvement; and a positive interferon-γ release assay. The model was validated by gender, clinical manifestations, endoscopic, and pathological findings in 49 patients (27 CD, 22 ITB). The sensitivity, specificity, and accuracy for diagnosis of ITB were 90.9%, 92.6%, and 91.8%, respectively. CONCLUSIONS: A Bayesian model based on the meta-analytic results is presented to estimate the probability of ITB and CD calibrated to local prevalence. This model can be applied to patients using a publicly available web application.

A Prospective Blinded Comparison of Video Capsule Endoscopy Versus Computed Tomography Enterography in Potential Small Bowel Bleeding: Clinical Utility of Computed Tomography Enterography.

GOALS: To compare the efficacy of video capsule endoscopy (VCE) with computed tomography enterography (CTE) in potential small bowel (SB) bleeding, and to identify factors predictive of a high diagnostic yield for CTE. BACKGROUND: In potential SB bleeding, CTE potentially detects some lesions missed by VCE, but few data have determined its clinical utility. STUDY: Consecutive patients with potential SB bleeding were prospectively enrolled. All underwent VCE and CTE within a 1-week interval. Definitive diagnoses were made by surgery or enteroscopy, except when a strategy of VCE and conservative management was suitable. The diagnostic yields and sensitivities of each investigation were measured. RESULTS: Fifty-two patients were recruited (41 with overt and 11 with occult bleeding); 36 received a definitive diagnosis. The diagnostic yields and sensitivities of VCE and CTE were 59.6% and 30.8% (P=0.004), and 72.2% and 44.4% (P=0.052), respectively. The combined sensitivity of VCE and CTE (88.9%) was significantly greater than VCE (P=0.03) or CTE (P<0.01) alone. VCE was better for ulcers, enteritis, and angiodysplasia, whereas CTE was better for tumors and Meckel diverticula. Age below 40 years and severe bleeding were associated with a higher diagnostic yield for CTE [odds ratios (95% confidence interval)=7.3 (1.04-51.4), P=0.046 and 6.1 (1.4-25.5), P=0.014, respectively]. CONCLUSIONS: Both investigations complement each other in the diagnosis of potential SB bleeding. CTE should be considered when VCE is negative. Age below 40 years and severe bleeding were independent predictors of a higher diagnostic yield for CTE.

Differentiating Clostridium difficile Colitis from Clostridium difficile Colonization in Ulcerative Colitis: A Role for Procalcitonin.

BACKGROUND/AIMS: Clostridium difficile infection (CDI) frequently complicates ulcerative colitis (UC) and can mimic disease flare. Differentiating UC flare from CDI remains a clinical challenge, particularly due to C. difficile colonization. Procalcitonin (PCT) is a serum biomarker for bacterial infections. We hypothesized that PCT would differentiate acute CDI from UC flare and C. difficile colonization. METHODS: A single-center prospective cohort study was conducted from 2013 to 2016. All UC patients with a stool sample for C. difficile testing were eligible. A total of 117 patients were enrolled, while 20 were excluded. Chart review was performed. RESULTS: Among 27 patients with CDI, median PCT was 60.7 (range 26-560.6) pg/mL, while among 90 patients without CDI, median PCT was 56.7 (range 25.1-2,252) pg/mL (p = 0.9). It was found that 14 patients with CDI responded completely to C. difficile treatment (CDI-R), while 8 patients did not and were diagnosed with UC flare (CDI-NR). For CDI-R, median PCT was 104.5 (range 26.3-560.6), compared to 40.3 (range 26.0-116.3) for CDI-NR (p = 0.036). CONCLUSIONS: In UC patients presenting with diarrhea, serum PCT was not significantly higher in UC patients with positive C. difficile testing. However, PCT was significantly elevated in CDI-R versus CDI-NR, suggesting that PCT may have utility in making this discrimination.

Imipramine for Treatment of Esophageal Hypersensitivity and Functional Heartburn: A Randomized Placebo-Controlled Trial.

OBJECTIVES: Tricyclic antidepressants could be effective in the treatment of symptoms related to hypersensitive esophagus through their pain-modulating effect. We therefore assessed the benefit of imipramine in patients with esophageal hypersensitivity and functional heartburn. METHODS: Patients with normal endoscopy findings and typical reflux symptoms despite standard-dose proton-pump inhibitor therapy underwent 24-h pH-impedance monitoring. Patients with established esophageal hypersensitivity or functional heartburn were randomly assigned to receive 8 weeks of either once-daily imipramine 25 mg (n=43) or placebo (n=40). The primary end point was satisfactory relief of reflux symptoms, defined as a >50% reduction in the gastroesophageal reflux disease score. The secondary end point was improvement in quality-of-life (QoL) as assessed by the 36-Item Short Form Health Survey score. RESULTS: Patients receiving imipramine did not achieve a higher rate of satisfactory relief of reflux symptoms than did patients receiving placebo (intention-to-treat (ITT) analysis: 37.2 vs. 37.5%, respectively; odds ratio (OR), 0.99; 95% confidence interval (CI), 0.41-2.41; per-protocol (PP) analysis: 45.5 vs. 41.2%, respectively; OR, 1.19; 95% CI, 0.45-3.13). Subgroup analysis to assess the efficacy of imipramine for either esophageal hypersensitivity or functional heartburn yielded similar results. Treatment with imipramine provided significant improvement of QoL by PP analysis (72±17 and 61±19, respectively; P=0.048), but ITT analysis did not reveal any differences between imipramine and placebo (68±19 and 61±19, respectively; P=0.26). Adverse events were similar in both groups; however, constipation was more common with imipramine than placebo (51.2 vs. 22.5%, respectively; P=0.01). CONCLUSIONS: Although low-dose imipramine shows potential QoL benefits, it does not relieve symptoms more effectively than does placebo in patients with either esophageal hypersensitivity or functional heartburn.

Intestinal capillariasis in the 21st century: clinical presentations and role of endoscopy and imaging.

BACKGROUND: Intestinal capillariasis is one of the common causes of malabsorption in the East. Reports emphasizing the roles of clinical, endoscopic and radiologic findings of intestinal capillariasis are limited. METHODS: Retrospective review of medical records of 26 patients diagnosed with intestinal capillariasis at Siriraj Hospital, Bangkok, Thailand between 2001- 2013. RESULTS: Clinical manifestations were chronic watery diarrhea (93%), chronic abdominal pain (70%), significant weight loss (92%), hypoalbuminemia (100%; 85% lower than 2.0 g/dL), and anemia (50%). The median duration of symptoms was 5.5 months (1-60 months). Parasites were found in stool in 15 patients (57%). In patients whose stool tests were initially negative, parasites were discovered in tissue biopsy from endoscopy in 1 from 10 esophagogastroduodenoscopies (EGD), 0 from 7 colonoscopies, 3 from 5 push enteroscopies, and 3 from 5 balloon-assisted enteroscopies (BAE). Endoscopic findings included scalloping appearance, mucosal cracking, and redness of mucosa. These endoscopic findings affected mostly at jejunum and proximal ileum. They were similar to celiac disease except duodenal involvement which is uncommon in capillariasis. Three patients underwent video capsule endoscopy (VCE) and typical abnormal findings were observed in all patients. Small bowel barium study showed fold thickening, fold effacement, and increased luminal fluid in 80% of patients, mainly seen at distal jejunum and ileum. CT findings were long segment wall thickening, enhanced wall, and fold effacement. Treatment with either albendazole or ivermectin cured all patients with most responding within 2 months. CONCLUSIONS: In endemic area, intestinal capillariasis should be considered if patients develop chronic watery diarrhea accompanied by significant weight loss and severe hypoalbuminemia. Stool examination had quite low sensitivities in making diagnosis in our study. Deep enteroscopy with biopsy guided by imaging or VCE may improve diagnostic yield. Empirical therapy may also be justifiable due to the very good response rate and less side effects.