Natural History and Outcomes of Individuals With Functional Bowel Disorder: A 9-year Population-Based Longitudinal Study.

INTRODUCTION: Long-term studies characterizing the natural history of functional bowel disorder (FBD) from community-based settings and exploring association with psychological factors are sparse. We aimed to evaluate the evolution of symptoms, health outcomes, and association of FBD with psychological disorders in Chinese population. METHODS: Individuals identified from random sampling of residents of Hangzhou, China, participated in a baseline survey in January 2010. Follow-up phone survey was conducted in December 2018. FBD was diagnosed based on Rome III criteria. RESULTS: Among 452 individuals (mean age 44.6 ± 15.3 years, 174 [38%] male) who completed the study, the prevalence of FBD was 36.3% (95% confidence interval [CI] 32.6-40.0%) at enrollment and 36.1% (95% CI 32.3-39.8%) at follow-up survey ( P = 0.94). However, 214 individuals (47%) had interval change in diagnosis. Although no difference in incidence of organic disease or death was observed, a higher proportion of patients with FBD (16/164, 9.8% vs 9/288, 3.1%; P = 0.003) compared with those without FBD received non-cancer-related abdominal and/or pelvic surgery during follow-up. FBD was associated with anxiety and/or depression at initial (adjusted odds ratio [AOR] = 1.7, 95% CI 1.7-2.7, P = 0.02) and follow-up (AOR = 8.0, 95% CI 3.2-20.0, P < 0.001) surveys. Diagnosis of FBD at baseline was associated with new-onset anxiety and/or depression at follow-up (AOR = 3.2, 95% CI 1.2-8.3, P = 0.01). DISCUSSION: Although the prevalence of FBD remained stable, transformation of symptoms was common over time. Patients with FBD may have increased risk of receiving non-cancer-related abdominal and/or pelvic surgery. FBD symptoms at baseline increased the risk of new-onset anxiety and/or depression by 3.2-fold over the next 9 years.

Prevalence and Persistent Shedding of Fecal SARS-CoV-2 RNA in Patients With COVID-19 Infection: A Systematic Review and Meta-analysis.

INTRODUCTION: The prevalence and shedding of fecal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA indicate coronavirus disease 2019 (COVID-19) infection in the gastrointestinal (GI) tract and likely infectivity. We performed a systemic review and meta-analysis to evaluate the prevalence and the duration of shedding of fecal RNA in patients with COVID-19 infection. METHODS: PubMed, Embase, Web of Science, and Chinese databases Chinese National Knowledge Infrastructure and Wanfang Data up to June 2020 were searched for studies evaluating fecal SARS-CoV-2 RNA, including anal and rectal samples, in patients with confirmed COVID-19 infection. The pooled prevalence of fecal RNA in patients with detectable respiratory RNA was estimated. The days of shedding and days to loss of fecal and respiratory RNA from presentation were compared. RESULTS: Thirty-five studies (N = 1,636) met criteria. The pooled prevalence of fecal RNA in COVID-19 patients was 43% (95% confidence interval [CI] 34%-52%). Higher proportion of patients with GI symptoms (52.4% vs 25.9%, odds ratio = 2.4, 95% CI 1.2-4.7) compared with no GI symptoms, specifically diarrhea (51.6% vs 24.0%, odds ratio = 3.0, 95% CI 1.9-4.8), had detectable fecal RNA. After loss of respiratory RNA, 27% (95% CI 15%-44%) of the patients had persistent shedding of fecal RNA. Days of RNA shedding in the feces were longer than respiratory samples (21.8 vs 14.7 days, mean difference = 7.1 days, 95% CI 1.2-13.0). Furthermore, days to loss of fecal RNA lagged respiratory RNA by a mean of 4.8 days (95% CI 2.2-7.5). DISCUSSION: Fecal SARS-CoV-2 RNA is commonly detected in COVID-19 patients with a 3-fold increased risk with diarrhea. Shedding of fecal RNA lasted more than 3 weeks after presentation and a week after last detectable respiratory RNA.

Modulation of the Gut Microbiota-farnesoid X Receptor Axis Improves Deoxycholic Acid-induced Intestinal Inflammation in Mice.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is associated with gut dysbiosis and dysregulation of bile acid metabolism. A high luminal content of deoxycholic acid (DCA) with consumption of a Westernised diet is implicated in the pathogenesis of IBD. The aim of the study is to explore the role of intestinal microbiota and bile acid metabolism in mice with DCA-induced intestinal inflammation. METHODS: Wild-type C57BL mice, 4 weeks old, were fed with AIN-93G (control diet), AIN-93G+0.2% DCA, AIN-93G+0.2% DCA+6 weeks of fexaramine (FXR agonist), or AIN-93G+0.2% DCA+antibiotic cocktail, for 24 weeks. Histopathology, western blotting, and qPCR were performed on the intestinal tissue. Faecal microbiota was analysed by 16S rDNA sequencing. Faecal bile acid and short chain fatty acid (SCFA) levels were analysed by chromatography. RESULTS: Gut dysbiosis and enlarged bile acid pool were observed in DCA-treated mice, accompanied by a lower farnesoid X receptor (FXR) activity in the intestine. Administration of fexaramine mitigated DCA-induced intestinal injury, restored intestinal FXR activity, activated fibroblast growth factor 15, and normalised bile acid metabolism. Furthermore, fexaramine administration increased the abundance of SCFA-producing bacteria. Depletion of the commensal microbiota with antibiotics decreased the diversity of the intestinal microbiota, attenuated bile acid synthesis, and reduced intestinal inflammation induced by DCA. CONCLUSIONS: DCA induced-intestinal inflammation is associated with alterations of gut microbiota and bile acid profiles. Interventions targeting the gut microbiota-FXR signalling pathway may reduce DCA-induced intestinal disease.

Deoxycholic Acid-Induced Gut Dysbiosis Disrupts Bile Acid Enterohepatic Circulation and Promotes Intestinal Inflammation.

BACKGROUND: A Western diet is a risk factor for the development of inflammatory bowel disease (IBD). High levels of fecal deoxycholic acid (DCA) in response to a Western diet contribute to bowel inflammatory injury. However, the mechanism of DCA in the natural course of IBD development remains unanswered. AIMS: The aim of this study is to investigate the effect of DCA on the induction of gut dysbiosis and its roles in the development of intestinal inflammation. METHODS: Wild-type C57BL/6J mice were fed an AIN-93G diet, either supplemented with or without 0.2% DCA, and killed at 24 weeks. Distal ileum and colon tissues were assessed by histopathological analysis. Hepatic and ileal gene expression was examined by qPCR, and the gut microbiota was analyzed by high-throughput 16S rRNA gene sequencing. HPLC-MS was used for fecal bile acid quantification. RESULTS: Mice fed the DCA-supplemented diet developed focal areas of ileal and colonic inflammation, accompanied by alteration of the composition of the intestinal microbiota and accumulation of fecal bile acids. DCA-induced dysbiosis decreased the deconjugation of bile acids, and this regulation was associated with the repressed expression of target genes in the enterohepatic farnesoid X receptor-fibroblast growth factor (FXR-FGF15) axis, leading to upregulation of hepatic de novo bile acid synthesis. CONCLUSIONS: These results suggest that DCA-induced gut dysbiosis may act as a key etiologic factor in intestinal inflammation, associated with bile acid metabolic disturbance and downregulation of the FXR-FGF15 axis.

Prophylactic clips to reduce delayed polypectomy bleeding after resection of large colorectal polyps: a systematic review and meta-analysis of randomized trials.

BACKGROUND AND AIMS: Prophylactic clips to prevent delayed polypectomy bleeding (DPB) after endoscopic resection of large colorectal polyps remains controversial. We performed a systematic review and meta-analysis to evaluate the efficacy of prophylactic clips for preventing DPB by synthesizing the results of randomized trials. METHODS: PubMed, Cochrane Library, and EMBASE were searched to October 2019 to identify randomized controlled trials evaluating the efficacy of placing prophylactic clips to reduce DPB after resection of large (≥10 mm) colorectal polyps. The primary outcome was DPB defined by GI bleeding after the conclusion of the colonoscopy. RESULTS: Eight studies (n = 3415) met the study criteria, all with a low risk of bias. The overall pooled incidence of DPB was 3.9% (95% confidence interval [CI], 2.4%-5.4%) in patients receiving endoscopic resection of colorectal polyps ≥10 mm. Placing prophylactic clips reduced DPB in patients receiving prophylactic clips (relative risk [RR], 0.61; 95% CI, 0.43-0.85; I2 = 37.8%) compared with no clips with a number needed to treat (NNT) of 52 (95% CI, 31-163). In stratified analyses, placing clips was associated with reduced risks of DPB in patients with polyps ≥20 mm (RR, 0.54; 95% CI, 0.35-0.84; I2 = 0.0%; NNT, 30), nonpedunculated morphology (RR, 0.54; 95% CI, 0.36-0.81; I2 = 0.0%; NNT, 39), and located proximal to the hepatic flexure (RR, 0.49; 95% CI, 0.31-0.78; I2 = 54.8%; NNT, 25) compared with no clips. CONCLUSIONS: Prophylactic clips after endoscopic resection of colorectal polyps ≥10 mm demonstrated a modest reduction in the risk of DPB. Larger reductions were observed in patients with polyps ≥20 mm, nonpedunculated morphology, or located proximal to the hepatic flexure.

Timing of Performing Endoscopic Retrograde Cholangiopancreatography and Inpatient Mortality in Acute Cholangitis: A Systematic Review and Meta-Analysis.

OBJECTIVES: Although early biliary drainage improves outcomes in patients with acute cholangitis, the optimal time to perform endoscopic retrograde cholangiopancreatography (ERCP) is controversial. Our aim was to evaluate the impact of timing of ERCP on mortality in hospitalized patients with acute cholangitis. METHODS: We searched PubMed, EMBASE, and The Cochrane Library (until February 2019) for studies evaluating the impact of timing of ERCP (<24, <48, and <72 hours from hospitalization) on outcomes in patients with acute cholangitis. The primary outcome was in-hospital mortality. RESULTS: Fourteen observational studies, including 84,063 patients (mean age = 66 ± 18), met the study criteria. The overall pooled in-hospital mortality with acute cholangitis was 1.9% (95% confidence interval [CI] 1.8%-7.6%), which increased to 4.3% (95% CI 1.8%-8.7%) when administrative database studies were excluded. In 9 studies, ERCP performed <24 compared with ≥24 hours decreased in-hospital mortality (odds ratio [OR] = 0.81, 95% CI 0.73-0.90; I = 0%). In 8 studies, ERCP performed <48 compared with ≥48 hours decreased in-hospital mortality (OR = 0.57, 95% CI 0.51-0.63; I = 0%). In 4 studies, ERCP performed <72 compared with ≥72 hours decreased in-hospital mortality (OR = 0.32, 95% CI 0.15-0.68; I = 0%). Furthermore, hospital stay was reduced in patients receiving ERCP <24 compared with ≥24 hours (mean difference [MD] = 3.2 days, 95% CI 2.3-4.1; I = 78%), <48 compared with ≥48 hours (MD = 3.6 days, 95% CI 2.1-5.1; I = 98%), and <72 compared with ≥72 hours (MD = 4.1 days, 95% CI 0.9-7.3; I = 63%). DISCUSSION: In observational studies, earlier ERCP performed in patients with acute cholangitis, even urgently performed <24 hours from presentation, was associated with reduced mortality. A randomized trial evaluating the impact of urgent ERCP on outcomes is needed.

Benefit of small dose antidepressants for functional dyspepsia: Experience from a tertiary center in eastern China.

BACKGROUND: Traditional treatment of functional dyspepsia (FD) is unsatisfactory in a subgroup of patients with FD, and the potential role of antidepressant medications also has not been definitely clarified. To provide more evidence for future optimal practice recommendations, we reviewed a 1-year clinical database of antidepressant agents applied in outpatients with FD. METHODS: Clinical presentations, treatment course, and outcomes were determined by chart review of patients referring to the functional gastrointestinal disorders specialist clinic. One hundred thirty patients with FD were included for further analysis. RESULTS: Patients were treated with different antidepressant drugs according to individual symptoms. The most commonly used drugs were flupenthixol melitracen and fluoxetine. Improvement and complete remission occurred in 93.8% and 54.6% of patients, respectively. There was a trend toward superior outcome for citalopram compared to sulpiride and mirtazapine in overall analysis. Meanwhile, regimens containing fluoxetine had significant increased remission rate compared to any other antidepressant regimens in postprandial distress syndrome subgroup analysis. Furthermore, older patients were more likely to achieve remission. However, sex and symptom duration were not associated with symptom remission. Finally, 11.5% of patients experienced adverse events. CONCLUSIONS: This retrospective cohort study indicated that small dose antidepressant therapy, especially citalopram and fluoxetine, is an effective and well tolerated treatment option for refractory FD.

Correlation between Serological Biomarkers and Disease Activity in Patients with Inflammatory Bowel Disease.

BACKGROUND: Current biomarkers have been routinely used noninvasive methods for assessing disease activity of inflammatory bowel disease (IBD), but none of them are specific. This study was aimed to determine the performance of the serological biomarkers for detecting disease activity in patients with IBD. METHODS: A prospective study that included 73 ulcerative disease (UC) subjects, 141 Crohn's disease (CD) subjects, and 30 of them complicated with C. difficile infection (CDI) were diagnosed at a single-institution IBD center. Disease activity was assessed using by Truelove and Witts criteria for UC and Harvey Bradshaw Simple Index for CD. Serological inflammatory biomarkers were compared in different severity groups. Receiver operator curve analyses assessed the performance of each biomarker in discriminating disease states. RESULTS: For UC patients, elevated monocyte counts, C-reactive protein (CRP), and decreased lymphocyte counts and lymphocyte/monocyte ratio (LMR) significantly differed between subjects with active and inactive UC. LMR of 3.1 was 76% sensitive and had a specificity of 67% for active UC. For CD patients, higher values of neutrophils, monocytes, neutrophil/lymphocyte ratio, CRP, fibrinogen, and lower values of LMR and hemoglobin were significantly different between subjects with active and inactive CD. None of the biomarkers included had a good correlation with disease activity (area under the ROC Curve < 0.70). CONCLUSIONS: A low LMR represents an inexpensive, readily available test with a promising value to identify disease activity in UC patients, whereas none of the inflammatory biomarkers showed a discriminative value in disease activity of CD.