Digestive Diseases and Sciences

Sharpening the Focus: Acupuncture Interrupts the Brain–Gut Vicious Cycle Underlying Functional Dyspepsia

The Emerging Epidemic of Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: True, True, and Related?

Inverted Yield Curve: The Alarming Rising Incidence of CRC in Young People

A Holistic Approach to Diagnosing and Treating Dysphagia Abstract We report a 39-year-old Native American female with an almost 20-year history of dysphagia that had increased in the 6 months prior to the initial evaluation. Investigation revealed a number of distinct esophageal disorders including Plummer–Vinson syndrome, gastroesophageal reflux disease with esophagitis, distal esophageal stricture, esophageal intramural pseudo-diverticulosis, and recurrent esophageal Candida infections. Although prolonged therapy with proton pump inhibitors, fluconazole, nystatin, and repeated esophageal balloon dilations relieved her symptoms, her prognosis remains uncertain.

LncRNA MALAT1 Promotes Ulcerative Colitis by Upregulating lncRNA ANRIL Abstract Background LncRNA MALAT1 contributes to the inflammatory responses induced by lipopolysaccharides (LPS), which shares similar pathogenesis with ulcerative colitis (UC), indicating the potential involvement of MALAT1 in UC. Methods Expression of MALAT1 and lncRNA ANRIL in both UC patients and healthy controls was analyzed by RT-qPCR. ROC curve analysis was used to evaluate the diagnostic value of MALAT1 for UC. Cell transfections were performed to analyze the interactions between MALAT1 and ANRIL. Cell apoptosis was analyzed by cell apoptosis assay. Results In the present study, we found that MALAT1 was upregulated in colonic mucosa tissues of UC patients in comparison with healthy controls. Plasma levels of MALAT1 were also higher in UC patients than in healthy controls, and upregulation of plasma MALAT1 distinguished UC patients from healthy controls. ANRIL was also upregulated in colonic mucosa tissues of UC patients than in that of healthy controls. ANRIL and MALAT1 were significantly and positively correlated in UC patients but not in healthy controls. Normal colonic epithelial cells with ANRIL overexpression showed no significantly changed MALAT1 overexpression, while MALAT1 overexpression led to promoted ANRIL expression. MALAT1 and ANRIL overexpression led to promoted apoptosis of FHCs. Conclusion MALAT1 promotes ulcerative colitis by upregulating ANRIL.

Microbiome and Its Role in Irritable Bowel Syndrome Abstract Irritable bowel syndrome (IBS) is an extremely common and often very debilitating chronic functional gastrointestinal disorder. Despite its prevalence, significant associated healthcare costs, and quality-of-life issues for affected individuals, our understanding of its etiology remained limited. However, it is now evident that microbial factors play key roles in IBS pathophysiology. Acute gastroenteritis following exposure to pathogens can precipitate the development of IBS, and studies have demonstrated changes in the gut microbiome in IBS patients. These changes may explain some of the symptoms of IBS, including visceral hypersensitivity, as gut microbes exert effects on the host immune system and gut barrier function, as well as the brain–gut axis. Microbial differences also appear to underlie the two main functional categories of IBS: diarrhea-predominant IBS (IBS-D) is associated with small intestinal bacterial overgrowth, which can be diagnosed by a positive hydrogen breath test, and constipation-predominant IBS (IBS-C) is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. Mechanistically, the pathogens that cause gastroenteritis and trigger subsequent IBS development produce a common toxin, cytolethal distending toxin B (CdtB), and antibodies raised against CdtB cross-react with the cytoskeletal protein vinculin and impair gut motility, facilitating bacterial overgrowth. In contrast, methane gas slows intestinal contractility, which may facilitate the development of constipation. While antibiotics and dietary manipulations have been used to relieve IBS symptoms, with varying success, elucidating the specific mechanisms by which gut microbes exert their effects on the host may allow the development of targeted treatments that may successfully treat the underlying causes of IBS.

Aggressive Percutaneous Catheter Drainage Protocol for Necrotic Pancreatic Collections Abstract Background Percutaneous catheter drainage (PCD) performed pro-actively for collections in acute pancreatitis (AP) is associated with better outcomes. However, there are only a few studies describing this protocol. Aim We aimed to evaluate an aggressive PCD protocol. Methods Consecutive patients with AP who underwent PCD with an aggressive protocol between January 2018 and January 2019 were included. This protocol involved catheter upsizing at a pre-specified interval (every 4–6 days) as well as drainage of all the new collections. The indications and technical details of PCD and clinical outcomes were compared with patients who underwent standard PCD. Results Out of the 185 patients with AP evaluated during the study period, 110 (59.4%) underwent PCD, all with the aggressive protocol. The historical cohort of standard PCD comprised of 113 patients. There was no significant difference in the indication of PCD and interval from pain onset to PCD between the two groups. The mean number of catheters was significantly higher in the aggressive PCD group (1.86 ± 0.962 vs. 1.44 ± 0.667, p = 0.002). Additional catheters were inserted in 54.2% of patients in aggressive group vs. 36.2% in the standard group (p = 0.006). Length of hospital stay and intensive care unit (ICU) stay were significantly longer in the standard PCD group (34.3 ± 20.14 vs. 27.45 ± 14.2 days, p < 0.001 and 10.46 ± 12.29 vs. 4.12 ± 8.5, p = 0.009, respectively). There was no significant difference in mortality and surgery between the two groups. Conclusion Aggressive PCD protocol results in reduced length of hospital stay and ICU stay and can reduce hospitalization costs.

Reduced Esophageal Contractility Is Associated with Dysplasia Progression in Barrett’s Esophagus: A Multicenter Cohort Study Abstract Background The incidence of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) continues to rise, and risk stratification of patients with BE is needed. Impaired esophageal motility is associated with gastroesophageal reflux disease; however, whether esophageal dysmotility is a risk factor for dysplasia progression in BE is incompletely understood. This study aimed to characterize esophageal motility patterns in patients with BE and identify physiologic factors associated with dysplasia progression in BE. Methods This multicenter retrospective study assessed data from adult patients with histologically confirmed BE who underwent high-resolution esophageal manometry from 1/2014 to 1/2018 at four tertiary care centers. Longitudinal data were collected when available among patients with non-dysplastic BE (NDBE) and separated as: no dysplastic progression or positive dysplastic progression. Multivariable logistic regression assessed for independent predictors of dysplasia progression. Results Among 193 patients, histology at index endoscopy identified 152 (79%) NDBE, 23 (12%) low-grade dysplasia, 14 (7%) high-grade dysplasia, and 4 (2%) EAC. Ninety-eight (51%) had abnormal esophageal motor function on manometry. Longitudinal data were available for 84 of 152 patients with initial NDBE. Twelve (14%) exhibited dysplastic progression to low-grade (6) or high-grade (6) dysplasia. Mean esophageal distal contractile integral was lower for patients that progressed [455 mmHg s cm (SD 515)] compared with patients who did not progress [987 mmHg s cm (SD 953); aOR 1.21 (95% CI 1.01, 1.44)]. Conclusion In this retrospective study of 193 BE patients, the majority exhibited abnormal esophageal motor function. Reduced esophageal contractility was independently associated with dysplastic progression in BE. Characterizing esophageal physiology in BE may help to risk stratify patients.

Fecal Microbiota Transplantation for Chronic Liver Diseases: Current Understanding and Future Direction Abstract Chronic liver disease is a major cause of morbidity and mortality worldwide. Even though effective treatments are now available for most chronic viral hepatitis, treatment options for other causes of chronic liver disease remain inadequate. Recent research has revealed a previously unappreciated role that the human intestinal microbiome plays in mediating the development and progression of chronic liver diseases. The recent remarkable success of fecal microbiota transplantation (FMT) in treating Clostridioides difficile demonstrates that the intestinal microbiota can be manipulated to obtain favorable therapeutic benefits and that FMT may become an important component of a total therapeutic approach to effectively treat hepatic disorders.

14-Day High-Dose Amoxicillin- and Metronidazole-Containing Triple Therapy With or Without Bismuth as First-Line Helicobacter pylori Treatment Abstract Background Amoxicillin, metronidazole, proton pump inhibitor, bismuth quadruple therapy had been shown to reliably achieve high eradication rates. The role of individual components remains undefined. Aim To identify the additional benefit/role of bismuth in amoxicillin, metronidazole, proton pump inhibitor, bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment. Methods This was a non-inferiority factorial design trial. Treatment-naive H. pylori-infected subjects were randomly (1:1) assigned to receive 14-day amoxicillin- and metronidazole-containing triple therapy consisting of esomeprazole 20 mg twice a day, amoxicillin 1 g, and metronidazole 400 mg both thrice daily with or without 220 mg bismuth twice a day. Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. Results From July 2018 to June 2019, a total of two hundred and sixteen subjects were randomized. Both therapies achieved high eradication rates. Per-protocol with bismuth = 97.9% (94/96, 95% CI 95.1–100%) and without bismuth = 94.7% (90/95, 95% CI 90.3–99.1%) (P = 0.43). Intent-to-treat analysis = 90.7% (98/108, 95% CI 85.2–96.2%) versus 88.9% (96/108, 95% CI 82.8–95.0%) with and without bismuth (P = 0.65). The two regimens were not inferior by intent-to-treat or per-protocol analyses. Metronidazole resistance did not affect the efficacy of either therapy. Conclusion Neither the presence nor absence of bismuth or metronidazole resistance reduced the effectiveness of triple therapy containing esomeprazole 20 mg twice a day, amoxicillin 1 g, and metronidazole 400 mg thrice daily in this population. The clinical trial was registered with ClinicalTrials.gov, NCT03557437.