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Background and purposeThe intestinal microbiome plays a primary role in the pathogenesis of neurodegenerative disorders and may provide an opportunity for disease modification. We performed a pilot clinical study looking at the safety of fecal microbiota transplantation (FMT), its effect on the microbiome, and improvement of symptoms in Parkinson's disease.MethodsThis was a randomized, double-blind placebo-controlled pilot study, wherein orally administered lyophilized FMT product or matching placebo was given to 12 subjects with mild to moderate Parkinson's disease with constipation twice weekly for 12 weeks. Subjects were followed for safety and clinical improvement for 9 additional months (total study duration 12 months).ResultsFecal microbiota transplantation caused non-severe transient upper gastrointestinal symptoms. One subject receiving FMT was diagnosed with unrelated metastatic cancer and was removed from the trial. Beta diversity (taxa) of the microbiome, was similar comparing placebo and FMT groups at baseline, however, for subjects randomized to FMT, it increased significantly at 6 weeks (p = 0.008) and 13 weeks (p = 0.0008). After treatment with FMT, proportions of selective families within the phylum Firmicutes increased significantly, while proportion of microbiota belonging to Proteobacteria were significantly reduced. Objective motor findings showed only temporary improvement while subjective symptom improvements were reported compared to baseline in the group receiving FMT. Constipation, gut transient times (NS), and gut motility index (p = 0.0374) were improved in the FMT group.ConclusionsSubjects with Parkinson's disease tolerated multi-dose-FMT, and experienced increased diversity of the intestinal microbiome that was associated with reduction in constipation and improved gut transit and intestinal motility. Fecal microbiota transplantation administration improved subjective motor and non-motor symptoms.Clinical trial registrationClinicalTrial.gov, identifier: NCT03671785.

The aim of this study was to determine if the quick Sepsis-Related Organ Failure Assessment (qSOFA) score assessed at and 48 hours after admission is prognostic for alcohol-induced acute pancreatitis (AAP) severity.This is a retrospective cohort review study of 161 patients admitted to a single academic hospital in Houston, TX, with the diagnosis of AAP. Receiver operator characteristics analysis and logistic regression were used to assess the diagnostic accuracy and prognostic ability of the qSOFA score.A qSOFA score of 2 or higher at and 48 hours after admission had a specificity of 94% or greater and sensitivity of 33% or higher for pancreatitis severity and need for intensive care admission, intubation, or vasopressors. The qSOFA score at and 48 hours after admission was prognostic of intensive care unit admission by an adjusted odds ratio of 48.5 (95% confidence interval [CI], 6.4-1013.3; Plt; 0.001) and 18.8 (95% CI, 2.2-467.3; Plt; 0.05), respectively. The qSOFA score at admission was prognostic of severe pancreatitis by an adjusted odds ratio of 35.3 (95% CI, 7.2-224.3; Plt; 0.001).A qSOFA score of 2 or higher is highly specific and prognostic of multiple clinical outcomes both at and 48 hours after admission in patients with AAP.

This study aims at prospectively evaluating the difference in the effect of cholecystokinin (CCK) and half-and-half milk (HHM) administered in the same patient on gallbladder contractility and correlation with clinical outcomes. Upon gallbladder visualization during standard hepatobiliary imaging, 0.02 μg/kg of CCK was injected over 3 min, and additional 30 min of dynamic imaging was obtained. Patients with gallbladder ejection fraction (GBEF)

IgA-coated bacteria in the gut (IgA-biome) provide a homeostatic function in healthy people through inhibition of microbial invaders and by protecting the epithelial monolayer of the gut. The laboratory methods used to detect this group of bacteria require flow cytometry and DNA sequencing (IgA-Seq). With dysbiosis (reduced diversity of the microbiome), the IgA-biome also is impaired. In the presence of enteric infection, oral vaccines, or an intestinal inflammatory disorder, the IgA-biome focuses on the pathogenic bacteria or foreign antigens, while in other chronic diseases associated with dysbiosis, the IgA-biome is reduced in capacity. Fecal microbiota transplantation (FMT), the use of fecal product from well-screened, healthy donors administered to patients with dysbiosis, has been successful in engrafting the intestine with healthy microbiota and metabolites leading to improve health. Through FMT, IgA-coated bacteria have been transferred to recipients retaining their immune coating. The IgA-biome should be evaluated in FMT studies as these mucosal-associated bacteria are more likely to be associated with successful transplantation than free luminal organisms. Studies of the microbiome pre- and post-FMT should employ metagenomic methods that identify bacteria at least at the species level to better identify organisms of interest while allowing comparisons of microbiota data between studies.

To elucidate the reasons for the decreased effectiveness of Vedolizumab (VDZ) treatment in patients with Crohn's disease (CD) previously treated (CD-T) with anti-TNF-α biologics.Immunohistochemical staining was performed on sections of formalin-fixed paraffin-embedded ileocolonic biopsies using antibodies for the mucosal addressin molecule (MAdCAM-1) and Etrolizumab.The mean number of MAdCAM-1 positive capillaries (MAdCAM-1-C) was 3 in controls, 8.5 in CD, 5.37 in CD-T, 5.7 in ulcerative colitis (UC), and 3.1 in lymphocytic colitis (LC) (Our results suggest that treatment with anti-TNF-α reduces the number of MAdCAM-1-C in CD, even in biopsies with high HAS. This suggests that high inflammation in such cases obviously failed to respond to anti-TNF-α, may be less dependent on the migration of a4b7-lymphocytes to the inflamed mucosa, and therefore may not optimally respond to VDZ treatment.Presented in part at the Digestive Diseases Week meeting, San Diego, CA, May 2019. Supported by Takeda Pharmaceuticals.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition driven by diverse genetic and nongenetic programs that converge to disrupt immune homeostasis in the intestine. We have reported that, in murine intestinal epithelium with telomere dysfunction, DNA damage-induced activation of ataxia-telangiectasia mutated (ATM) results in ATM-mediated phosphorylation and activation of the YAP1 transcriptional coactivator, which in turn up-regulates pro-IL-18, a pivotal immune regulator in IBD pathogenesis. Moreover, individuals with germline defects in telomere maintenance genes experience increased occurrence of intestinal inflammation and show activation of the ATM/YAP1/pro-IL-18 pathway in the intestinal epithelium. Here, we sought to determine the relevance of the ATM/YAP1/pro-IL-18 pathway as a potential driver of IBD, particularly older-onset IBD. Analysis of intestinal biopsy specimens and organoids from older-onset IBD patients documented the presence of telomere dysfunction and activation of the ATM/YAP1/precursor of interleukin 18 (pro-IL-18) pathway in the intestinal epithelium. Employing intestinal organoids from healthy individuals, we demonstrated that experimental induction of telomere dysfunction activates this inflammatory pathway. In organoid models from ulcerative colitis and Crohn's disease patients, pharmacological interventions of telomerase reactivation, suppression of DNA damage signaling, or YAP1 inhibition reduced pro-IL-18 production. Together, these findings support a model wherein telomere dysfunction in the intestinal epithelium can initiate the inflammatory process in IBD, pointing to therapeutic interventions for this disease.

Unlike eosinophilic esophagitis (EoE), there is no consensus on the minimum number of intraepithelial lymphocytes (IEL) that is diagnostic of lymphocytic esophagitis (LyE). The aim of this study was to determine whether significant correlations exist between the numbers of intraepithelial lymphocytes (IEL) in esophageal biopsies and clinical and endoscopic manifestations usually associated with EoE.HE slides from esophageal biopsies from 330 patients were reviewed. The number of IEL and intraepithelial eosinophils (IEE) per mmAs expected, a higher number of IEE was significantly associated with food impaction (In esophageal biopsies, increased IEL has no significant correlation with food impaction or dysphagia or with esophageal stricture, rings, or furrows. There is significant variation in the number of IEL depending on the season when the biopsy is obtained, which has not been previously reported.

Clostridioides difficile infection (CDI), formerly known as Clostridium difficile, continues to be the most common healthcare-associated infection worldwide. With the shifting epidemiology towards higher a incidence of community-acquired CDI and the continued burden on the healthcare system posed by high rates of CDI recurrence, there has been an impetus to advance the diagnostic testing and treatment strategies. Recent advancements over the past decade have led to rapidly changing guidelines issued by the Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases. With our comprehensive review, we aim to summarize the latest advances in diagnosing and treating CDI and thus attempt to help readers guide best practices for patient care. This article also focusses on cost-effectiveness of various therapies currently available on the market and provides an analysis of the current evidence on a relatively new monoclonal antibody therapy, Bezlotoxumab, to treat recurrent CDI.

Clostridioides difficile infection (CDI), formerly known as Clostridium difficile, continues to be the most common healthcare-associated infection worldwide. With the shifting epidemiology towards higher a incidence of community-acquired CDI and the continued burden on the healthcare system posed by high rates of CDI recurrence, there has been an impetus to advance the diagnostic testing and treatment strategies. Recent advancements over the past decade have led to rapidly changing guidelines issued by the Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases. With our comprehensive review, we aim to summarize the latest advances in diagnosing and treating CDI and thus attempt to help readers guide best practices for patient care. This article also focusses on cost-effectiveness of various therapies currently available on the market and provides an analysis of the current evidence on a relatively new monoclonal antibody therapy, Bezlotoxumab, to treat recurrent CDI.

Aquaporin-5 (AQP5) is a member of a family of water channel proteins involved in the bidirectional transfer of water across cell membranes. Lymphocytic colitis (LC) and collagenous colitis (CC) are clinically similar diseases characterized by chronic watery diarrhea in patients with usually unremarkable colonic mucosa on colonoscopy. The aim of this study was to determine whether AQP5 expression in colonic epithelium is altered in LC and CC.Sections of formalin-fixed and paraffin-embedded colorectal biopsies from three control patients (CTL), 8 patients with chronic non-bloody diarrhea with biopsies negative for active inflammation or significant distortion (CTL-D), 8 patients with LC, and 5 with CC were stained for AQP5 using immunohistochemistry. The staining intensity was scored as 3 (strong), 2 (intermediate), 1 (weak), or 0 (no staining). Statistical analysis was performed using Prism 7 Statistical Soft-ware.AQP5 was strongly expressed (score 3) in the epithelial cells in all three CTL cases and all 8 CTL-D cases. In the 5 cases of CC, 3(60%) had score 3 and 2(40%) had score 2, but none had a score of 1 or 0. Of the 8 LC cases, 2(25%) had score 3, 3 had score 2(37.5%), and 3 had score 1(37.5%) (Colorectal AQP5 expression is reduced in most cases of LC. Markedly reduced AQP5 expression in LC may identify a subset of patients with suboptimal response to enteric steroid treatment. Additional larger studies are needed to confirm these findings.This abstract was presented in part at Digestive Diseases Week in San Diego, CA, May 2019.

Introduction Prognostic factors are needed to aid clinicians in managing Covid‐19, a respiratory illness. Lymphocytopenia has emerged as a simply obtained laboratory value that may correlate with prognosis. Methods In this article, we perform a retrospective cohort review study on patients admitted to one academic hospital for Covid‐19 illness. We analyzed basic demographic, clinical, and laboratory data to understand the relationship between lymphocytopenia at the time of hospital admission and clinical outcomes. Results We discovered that lymphocyte count is lower (P = .01) and lymphocytopenia more frequent by an odds ratio of 3.40 (95% CI: 1.06‐10.96; P = .04) in patients admitted to the Intensive Care Unit (ICU), a marker of disease severity, relative to those who were not. We additionally find that patients with lymphocytopenia were more likely to develop an acute kidney injury (AKI), a marker of organ failure, during admission by an odds ratio of 4.29 (95% CI: 1.35‐13.57; P = .01). Conclusion This evidence supports the hypothesis that lymphocytopenia can be an early, useful, and easily obtained, prognostic factor in determining the clinical course and disease severity of a patient admitted to the hospital for Covid‐19.

Prognostic markers are needed to understand the disease course and severity in patients with Covid-19. There is evidence that Covid-19 causes gastrointestinal symptoms and abnormalities in liver enzymes. We aimed to determine if hepatobiliary laboratory data could predict disease severity in patients with Covid-19. In this retrospective, single institution, cohort study that analyzed patients admitted to a community academic hospital with the diagnosis of Covid-19, we found that elevations of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) at any time during hospital admission increased the odds of ICU admission by 5.12 (95% CI: 1.55–16.89; p = 0.007), 4.71 (95% CI: 1.51–14.69; p = 0.01) and 4.12 (95% CI: 1.21–14.06, p = 0.02), respectively. Hypoalbuminemia found at the time of admission to the hospital was associated with increased mortality (p = 0.02), hypotension (p = 0.03), and need for vasopressors (p = 0.02), intubation (p = 0.01) and hemodialysis (p = 0.002). Additionally, there was evidence of liver injury: AST was significantly elevated above baseline in patients admitted to the ICU (54.2 ± 15.70 U/L) relative to those who were not (9.2 ± 4.89 U/L; p = 0.01). Taken together, this study found that hypoalbuminemia and abnormalities in hepatobiliary laboratory data may be prognostic factors for disease severity in patients admitted to the hospital with Covid-19.

The caudal-related homeobox transcription factor 2 (CDX2) plays an important role in intestinal epithelial differentiation, proliferation, migration, and adhesion. It has been previously reported that TNF-α reduces CDX2 expression in cultured colon epithelial cells in a dose-dependent manner, and that this effect was reduced by adding the anti-TNF-α drug infliximab to the culture medium. The aim of this study was to determine whether CDX2 expression is reduced in biopsies from patients with Crohn's disease (CD), and whether treatment with anti-TNF-α drugs reverses CDX2 downregulation in these patients.Sections of ileocolonic biopsy tissues from patients with CD, CD treated with anti-TNF-α biologics (CD-T), and controls were stained for CDX2 and evaluated using OTMIAS digital image analysis.CDX2 expression in biopsies from patients with CD and CD-T was lower than in controls (Although CDX2 is downregulated in CD, it did not revert to normal in patients treated with anti-TNF-α biologics.

Reduction in diversity of the intestinal microbiome (dysbiosis) is being identified in many disease states, and studies are showing important biologic contributions of microbiome to health and disease. Fecal microbiota transplantation (FMT) is being evaluated as a way to reverse dysbiosis in diseases and disorders in an attempt to improve health. The published literature was reviewed to determine the value of FMT in the treatment of medical disorders for which clinical trials have recently been conducted. FMT is effective in treating recurrent C. difficile infection in one or two doses, with many healthy donors providing efficacious fecal-derived products. In inflammatory bowel disease (IBD), FMT may lead to remission in approximately one-third of moderate-to-severe illnesses with one study suggesting that more durable FMT responses may be seen when used once medical remissions have been achieved. Donor products differ in their efficacy in treatment of IBD. Combining donor products has been one way to increase the potential value of FMT in treating chronic disorders. FMT is being explored in a variety of clinical settings affecting different organ systems outside CDI, with positive preliminary signals, in treatment of functional constipation, immunotherapy-induced colitis, neurodegenerative disease, as well as prevention of cancer-related disorders like graft versus host disease and decolonization of patients with recurrent urinary tract infection due to antibiotic-resistant bacteria. Currently, intense research is underway to see how the microbiome products like FMT can be harnessed for health benefits.

Germline telomere maintenance defects are associated with an increased incidence of inflammatory diseases in humans, yet whether and how telomere dysfunction causes inflammation are not known. Here, we show that telomere dysfunction drives pATM/c-ABL-mediated activation of the YAP1 transcription factor, up-regulating the major pro-inflammatory factor, pro-IL-18. The colonic microbiome stimulates cytosolic receptors activating caspase-1 which cleaves pro-IL-18 into mature IL-18, leading to recruitment of interferon (IFN)-γ-secreting T cells and intestinal inflammation. Correspondingly, patients with germline telomere maintenance defects exhibit DNA damage (γH2AX) signaling together with elevated YAP1 and IL-18 expression. In mice with telomere dysfunction, telomerase reactivation in the intestinal epithelium or pharmacological inhibition of ATM, YAP1, or caspase-1 as well as antibiotic treatment, dramatically reduces IL-18 and intestinal inflammation. Thus, telomere dysfunction-induced activation of the ATM-YAP1-pro-IL-18 pathway in epithelium is a key instigator of tissue inflammation., How telomere dysfunction is directly linked to inflammation in humans is currently unclear. Here the authors reveal that telomere dysfunction drives activation of the YAP1 transcription factor, up-regulating the pro inflammatory factor, pro-IL-18 thus revealing a link between telomere dysfunction and initiation of intestinal inflammation.

CpG island methylator phenotype (CIMP)-positive colorectal cancers (CRC) and CRC with microsatellite instability (MSI) were reported to have a decreased expression of estrogen receptor, beta1 (ER-β1), and methylation accompanied by decreased expression for the caudal-related homeobox, transcription factor 2 (CDX2). While precursor lesions of these cancers, known as sessile serrated adenomas (SSA), were found to have decreased CDX2 expression, the status of ER-β1 expression in SSA is unknown. The aim of this study is to determine ER-β1 expression in SSA and its relation to CDX2 expression.Sections of formalin fixed and paraffin embedded tissue from 62 consecutive cases of SSA were stained by immunohistochemistry for ER-β1 and CDX2. SSA with ER-β1 or CDX2 expression similar to that of a normal colon were scored as 0, while those with a loss of expression in10% of SSA crypts as 1, 11-25% as 2, 26-50% as 3, 51-75% as 4, and CDX2 loss in75% of the SSA crypts scored as 5.There is a significant correlation between a loss of CDX2 and the loss of ER-β1 scores in SSA (Our findings show significant downregulation of both ER-β1 and CDX2 expression in SSA, especially in the right colon. These findings suggest that ER-β1 downregulation plays a significant role in the malignant progression of SSA.

Context.—The cause of pancreatic acinar metaplasia (PAM) at the distal esophagus/esophagogastric junction is still controversial. Whereas some authors believe it is congenital, others believe it is acquired because of inflammation of the gastric cardia, and more recently it was proposed to be due to chronic proton pump inhibitor use based on a study in rats.Objective.—To determine whether there is correlation between chronic proton pump inhibitor use and PAM in humans. We also investigated the correlation between several clinical and pathologic factors and PAM.Design.—Four hundred forty-four consecutive biopsies from the distal esophagus/esophagogastric junction were reviewed for the presence of PAM, which was then correlated with several clinical and pathologic findings.Results.—Pancreatic acinar metaplasia was found in 71 patients (16%). Pancreatic acinar metaplasia was significantly associated with patient age younger than 51 years (P < .001), chronic carditis (P = .01), and chronic proton pump inhibitor use (P = .008). Surprisingly, we also found significant association between PAM and chronic nonsteroidal anti-inflammatory drug use (P < .001). These associations, including that with chronic nonsteroidal anti-inflammatory drug use, remained significant in multivariate analysis.Conclusions.—Our findings confirm the previous reports of significant association between PAM and chronic carditis and the findings from animal studies of association with chronic proton pump inhibitor use. The strong association with chronic nonsteroidal anti-inflammatory drug use has not been previously reported and warrants further studies.

Raman spectroscopy provides diagnostic information by detecting disease-associated subtle biochemical changes in the tissue. Yet the physiological variations among normal subjects could confound data interpretation and thus compromise the sensitivity in disease discrimination. We analyzed Raman spectra acquired from colon tissue in vivo through an endoscopic Raman system and evaluated potential physiological factors affecting tissue biochemistry. Fifty-six healthy patients scheduled for colonoscopy screening were enrolled in the study. Intra-subject variability was evaluated via univariate analysis by comparing the intensities of major Raman bands from different anatomical locations. Inter-subject variability was investigated based on various physiological variables, such as age, gender, ethnicity (White/Caucasian, African American, and Hispanic), and body mass index (BMI). Both univariate analysis and principal component analysis-based multivariate analysis were implemented for the investigation of inter-subject variability. The differences among certain physiological variables were further analyzed after accounting for intra-subject variation by generalized estimating equation method due to its advantage in handling repeated measurements. The results showed that physiological factors including gender, ethnicity, age, BMI, and anatomical locations along the colon were significant sources of variability, resulting from different abundance in lipids and proteins. Further correlation analysis revealed that the variability from gender, ethnicity, and age is significantly associated with that from BMI, indicating that BMI might be the key contributor to the inter-subject variability in the spectra. This study suggested the importance of including normal variability, especially BMI and anatomical locations, into the interpretation of Raman spectra for in vivo application. Copyright © 2017 John Wiley & Sons, Ltd.

INTRODUCTION: Prognostic markers are needed to understand the disease course and severity in patients with Covid-19, a viral respiratory illness that causes systemic symptoms However, there is no model to date that evaluates the complexity of this illness We hypothesized that the MELD-Na score would be associated with disease severity in patients with Covid-19 METHODS: This is an IRB approved, retrospective, single institution, cohort study that analyzed patients admitted to a community academic hospital with the diagnosis of Covid-19 between March, 1st 2020 and June 11th, 2020 The primary outcome was mortality at 30 days based on MELD-Na score calculated at the time of admission Secondary outcomes included the development of an Acute Kidney Injury (AKI), need for hemodialysis (HD), need for vasopressor hemodynamic support, need for intubation and hospital stay lasting longer than 7 days RESULTS: The sample size consisted of 99 patients: admission data to calculate a MELD-Na score was available for 63 patients (63%) The MELD-Na score was found to be significantly higher in those who died at 30 days (14 38±6 92) after discharge relative to those who survived (9 68±5 69;P = 0 03);the odds of death at 30 days with a MELD-Na score greater than 10 was 9 00 (95% CI: 2 29, 35 50;P = 0 001) Patients with a MELD-Na score greater than 10 were more likely to have an AKI by an odds ratio (OR) of 3 31 (95% CI: 1 08, 10 17, P = 0 03), need HD by an OR of 9 69 (95% CI: 1 74, 53 96, P = 0 007), need vasopressor support by an OR of 4 55 (95% CI: 1 22, 16 99, P = 0 02) and stay in the hospital longer than 7 days by an OR of 4 17 (95% CI: 1 05, 16 47;P = 0 03) CONCLUSION: The MELD-Na score was found to be higher in patients with Covid-19 who died relative to those who survived at 30 days after discharge A MELD-Na score greater than 10 was prognostic of multiple clinical outcomes, including 30-day all cause mortality, development of an AKI, need for HD, need for vasopressors and longer hospital stay Thus, the MELD-Na score serves as a useful clinical scoring system for prognosis in patients admitted to the hospital with Covid-19 (Table Presented)

INTRODUCTION: Prognostic markers are needed to understand the disease course and severity in patients with Covid-19, a respiratory viral illness There is evidence that Covid-19 causes gastrointestinal symptoms and abnormalities in liver enzymes We aimed to determine if hepatobiliary laboratory data could predict disease severity in patients with Covid-19 METHODS: This is an IRB approved, retrospective, single institution, cohort study that analyzed patients admitted to a community academic hospital with the diagnosis of Covid-19 between March, 1st 2020 and May 5th, 2020 The primary outcome was the need for Intensive Care Unit (ICU) admission based on elevations in transaminases, Alkaline Phosphatase (AP) and Total Bilirubin (TB) Secondary outcomes included mortality, development of Acute Kidney Injury (AKI) or hypotension and need for supplemental oxygen RESULTS: Sixty patients were included in the analysis Elevation of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) increased the odds of ICU admission by 5 12 (95% CI: 1 55,16 89;P = 0 007), 4 71 (95% CI: 1 51,14 69;P = 0 01) and 4 12 (95% CI: 1 21,14 06, P = 0 02), respectively Hypoalbuminemia was associated with increased mortality by an odds ratio of 6 79 (CI: 1 27-36 34, P = 0 02) Additionally, there was evidence of liver injury: the change in AST during admission above baseline was significantly higher in patients admitted to the ICU (54 2±15 70 U/L) relative to those who were not (9 2±4 89 U/L;P = 0 01) CONCLUSION: This study found that hypoalbuminemia and abnormalities in hepatobiliary laboratory data are prognostic factors for disease severity in patients admitted to the hospital with Covid-19 Additionally, there may be evidence of liver injury in Covid-19 patients that is more severe in those admitted to the ICU (Table Presented)

Inflammatory bowel disease (IBD) characterized by chronic intestinal inflammation and intestinal microbial dysbiosis present a major risk factor in the development of colorectal cancer. Previously, dietary polyphenols from mango (Mangifera indica L.) such as gallotannins and gallic acid have been shown to mitigate intestinal inflammation and carcinogenesis, as well as modulate intestinal microbial composition. To further translate findings from preclinical models, we hypothesized that mango polyphenols possess anti-inflammatory and microbiome-modulatory activities and may improve symptoms of IBD, reduce biomarkers for inflammation and modulate the intestinal microbiome when administered as an adjuvant treatment in combination with conventional medications in patients with mild to moderate IBD. In this study, ten participants received a daily dose of 200–400 g of mango pulp for 8 weeks ( NCT02227602 ). Mango intake significantly improved the primary outcome Simple Clinical Colitis Activity Index (SCCAI) score and decreased the plasma levels of pro-inflammatory cytokines including interleukin-8 (IL-8), growth-regulated oncogene (GRO) and granulocyte macrophage colony-stimulating factor (GM-CSF) by 16.2% (P = .0475), 25.0% (P = .0375) and 28.6% (P = .0485), all factors related to neutrophil-induced inflammation, respectively. Mango intake beneficially altered fecal microbial composition by significantly increasing the abundance of Lactobacillus spp., Lactobacillus plantarum, Lactobacillus reuteri and Lactobacillus lactis, which was accompanied by increased fecal butyric acid production. Therefore, enriching diet with mango fruits or potentially other gallotannin-rich foods seems to be a promising adjuvant therapy combined with conventional medications in the management of IBD via reducing biomarkers of inflammation and modulating the intestinal microbiota.

Background Fecal microbiota transplantation (FMT) via colonoscopy or enema has become a commonly used treatment of recurrent C. difficile infection (CDI). Aims To compare the safety and preliminary efficacy of orally administered lyophilized microbiota product compared with frozen product by enema. Methods In a single center, adults with ≥ 3 episodes of recurrent CDI were randomized to receive encapsulated lyophilized fecal microbiota from 100–200 g of donor feces (n = 31) or frozen FMT from 100 g of donor feces (n = 34) by enema. Safety during the three months post FMT was the primary study objective. Prevention of CDI recurrence during the 60 days after FMT was a secondary objective. Fecal microbiome changes were examined in first 39 subjects studied. Results Adverse experiences were commonly seen in equal frequency in both groups and did not appear to relate to the route of delivery of FMT. CDI recurrence was prevented in 26 of 31 (84%) subjects randomized to capsules and in 30 of 34 (88%) receiving FMT by enema (p = 0.76). Both products normalized fecal microbiota diversity while the lyophilized orally administered product was less effective in repleting Bacteroidia and Verrucomicrobia classes compared to frozen product via enema. Conclusions The route of delivery, oral or rectal, did not influence adverse experiences in FMT. In preliminary evaluation, both routes appeared to show equivalent efficacy, although the dose may need to be higher for lyophilized product. Spore-forming bacteria appear to be the most important engrafting organisms in FMT by the oral route using lyophilized product. Trial registration ClinicalTrials.gov NCT02449174

ummary Background Faecal microbiota transplantation (FMT) has become routine in managing recurrent C. difficile infection (CDI) refractory to antibiotics. Aim To compare clinical response and improvements in colonic microbiota diversity in subjects with recurrent CDI using different donor product. Methods Seventy-two subjects with ≥3 bouts of CDI were randomised in a double-blind study to receive fresh, frozen or lyophilised FMT product via colonoscopy from 50 g of stool per treatment from eight healthy donors. Recipients provided stools pre- and 7, 14 and 30 days post-FMT for C. difficile toxin and, in a subset, microbiome composition by 16S rRNA gene profiling. Results Overall resolution of CDI was 87% during 2 months of follow-up after FMT. Stool samples before FMT had significantly decreased bacterial diversity with a high proportion of Proteobacteria compared to donors. Cure rates were highest for the group receiving fresh product seen in 25/25 (100%), lowest for the lyophilised product 16/23 (78%; P = 0.022 vs. fresh and 0.255 vs. frozen) and intermediate for frozen product 20/24 (P = 0.233 vs. fresh). Microbial diversity was reconstituted by day 7 in the subjects receiving fresh or frozen product. Improvement in diversity was seen by day 7 in those randomised to lyophilised material with reconstitution by 30 days. Conclusions Comparative efficacy in faecal microbiota transplantation was observed in subjects receiving fresh or frozen faecal product from the same donors. The lyophilised product had a slightly lowered efficacy compared with fresh product, but it resembled other treatments in microbial restoration 1 month after faecal microbiota transplantation.

Background and study aims: Gastric antral vascular ectasia (GAVE) is a known cause of gastrointestinal bleeding and chronic iron deficiency anemia. Endoscopic therapy with argon plasma coagulation (APC) is widely used for treatment of GAVE, but most patients continue to require repeated blood transfusions and multiple endoscopic procedures (refractory GAVE). We describe our initial experience regarding safety and efficacy of radiofrequency ablation (RFA) therapy in treating patients with refractory GAVE. Patients and methods: We prospectively enrolled seven patients with refractory GAVE who had multiple prior treatments with APC. These patients were treated with RFA (HALO90 ULTRA Ablation Catheter System; Covidien, GI Solutions, Sunnyvale, CA) at Ertan Digestive Disease Center at our tertiary University Hospital. Results: Seven patients underwent a total of 12 RFA procedures for treatment of refractory GAVE. The median number of RFA procedures was 2 (Range, 1 – 3). Average pre- and post-procedural hemoglobin were 9.3 g/dL and 10.16 g/dL, respectively. Five of seven patients (71 %) were transfusion-free after the RFA treatments while two patients continued to require blood transfusions. There were no complications in this series. Conclusion: RFA can be an effective alternative to APC for treatment of GAVE refractory to previous endoscopic therapy. Additional studies are needed to identify which subset of patients will benefit the most with RFA treatment.

Inflammatory bowel disease (IBD) is an idiopathic disease that is typically characterized by chronic inflammation of the gastrointestinal tract. Recently much effort has been devoted to the development of novel diagnostic tools that can assist physicians for fast, accurate, and automated diagnosis of the disease. Previous research based on Raman spectroscopy has shown promising results in differentiating IBD patients from normal screening cases. In the current study, we examined IBD patients in vivo through a colonoscope-coupled Raman system. Optical diagnosis for IBD discrimination was conducted based on full-range spectra using multivariate statistical methods. Further, we incorporated several feature selection methods in machine learning into the classification model. The diagnostic performance for disease differentiation was significantly improved after feature selection. Our results showed that improved IBD diagnosis can be achieved using Raman spectroscopy in combination with multivariate analysis and feature selection.

Clostridium difficileinfection (CDI) has become the most frequently reported health care-associated infection in the United States [1]. As the incidence of CDI rises, so too does the burden it produces on health care and society. In an attempt to decrease the burden of CDI and provide the best outcomes for patients affected by CDI, there have been many recent advancements in the understanding, diagnosis, and management of CDI. In this article, we review the current recommendations regarding CDI testing and treatment strategies.

Clostridium difficile infection (CDI) has become the most frequently reported health care-associated infection in the United States [1]. As the incidence of CDI rises, so too does the burden it produces on health care and society. In an attempt to decrease the burden of CDI and provide the best outcomes for patients affected by CDI, there have been many recent advancements in the understanding, diagnosis, and management of CDI. In this article, we review the current recommendations regarding CDI testing and treatment strategies.

Mucosal surfaces of the gut are colonized by large numbers of heterogeneous bacteria that contribute to intestinal health and disease. In genetically susceptible individuals, a 'pathogenic community' may arise, whereby abnormal gut flora contributes to alterations in the mucosa and local immune system leading to gastrointestinal disease. These diseases include enteric infections, such as Clostridium difficile infection, small intestinal bacterial overgrowth, functional gastrointestinal disorders (including IBS), IBD and colorectal cancer. Prebiotics, probiotics and synbiotics (a combination of prebiotics and probiotics) have the capacity to reverse pathologic changes in gut flora and local immunity. Intestinal health and disease need to be thoroughly characterized to understand the interplay between the indigenous microbiota, the immune system and genetic host factors. This Review provides a broad overview of the importance of the intestinal microbiota in chronic disorders of the gut.

Summary Background Aspirin chemoprevention combined with colonoscopy screening is not cost-effective for the general population. However, the cost-effectiveness of aspirin in individuals with prior adenoma resection has not been evaluated. Aim To evaluate the cost-effectiveness of aspirin chemoprevention alone and in combination with colonoscopy surveillance in patients with prior adenoma resection. Methods A model of the natural history of individuals with a history of endoscopic polypectomy was constructed. Four strategies were compared: (i) no intervention, (ii) routine colonoscopy surveillance, (iii) aspirin chemoprevention alone, and (iv) aspirin therapy combined with colonoscopy. Results Compared with no intervention, all other strategies were more costly but were associated with gains in years of life saved. Aspirin chemoprevention alone was associated with a gain of 0.0092 years, whereas routine colonoscopic surveillance and combination strategy were associated with further gains in years of life saved (0.0124 and 0.0138 years, respectively). Compared with no intervention, the incremental cost-effectiveness ratio of routine colonoscopy surveillance was $78 226 per year of life saved, and the incremental cost-effectiveness ratio of combination aspirin and colonoscopy was $60 942 per year of life saved. Conclusion Aspirin chemoprevention combined with colonoscopic surveillance in post-polypectomy patients may be considered a cost-effective strategy.

Both endoscopic and surgical drainage procedures are effective palliative methods for malignant biliary obstruction. Surgical drainage is still preferred in developing countries due to the high cost of procuring metal biliary stents. The aim of this study was to evaluate the quality of life and the cost of care in patients with metastatic pancreatic cancer after endoscopic biliary drainage and surgical drainage.This is a prospective, randomized controlled trial conducted in a tertiary referral center in Brazil. Patients with biliary obstruction due to metastatic pancreatic cancer and liver metastasis, but without gastric outlet obstruction, were included in the study. Endoscopic biliary drainage with the insertion of a metal stent into the bile duct was compared with the surgical drainage procedure (choledochojejunostomy and gastrojejunostomy). Quality of life was assessed before, and 30 days, 60 days, and 120 days after the drainage procedure. The cost of drainage procedure, cost during the first 30 days and the total cost from drainage procedure to death were calculated.Of the 273 patients with pancreatic malignancy seen at our hospital between July 2001 and October 2004, 35 patients were eligible for the study, and 30 agreed to participate in the study. Both surgical and endoscopic drainage procedures were successful, without any mortality in the first 30 days. The cost of biliary drainage procedure (US dollars 2,832 +/- 519 vs 3,821 +/- 1,181, p= 0.031), the cost of care during the first 30 days after drainage (US dollars 3,122 +/- 877 vs 6,591 +/- 711, p= 0.001), and the overall total cost of care that included initial care and subsequent interventions and hospitalizations until death (US dollars 4,271+/- 2,411 vs 8,321 +/- 1,821, p= 0.0013) were lower in the endoscopy group compared with the surgical group. In addition, the quality of life scores were better in the endoscopy group at 30 days (p= 0.042) and 60 days (p= 0.05). There was no difference between the two groups in complication rate, readmissions for complications, and duration of survival.Endoscopic biliary drainage is cheaper and provides better quality of life in patients with biliary obstruction and metastatic pancreatic cancer.

Travelers' diarrhea occurs when persons move from industrialized regions to developing countries with reduced hygiene. Bacterial enteropathogens from ingested food are the primary causes. Although it is possible to reduce the occurrence of illness by careful selection of food and beverages, travelers do not seem willing to restrict their diets. Diarrhea is associated with a disability of 24 hours per episode, interfering with travel plans and, of even greater concern, post-diarrhea irritable bowel syndrome (IBS) occurs in up to 10% of patients. The use of rifaximin, a poorly absorbed drug, is likely to become common as an attempt to prevent diarrhea and post-infectious IBS. All travelers to high-risk areas should take with them an effective antibacterial drug (rifaximin, fluoroquinolones, or azithromycin) for self-treatment of diarrhea occurring during travel. Additional work is needed to improve the hygienic conditions found in the developing world into which susceptible persons travel.

Background Probiotics are microorganisms that are ingested either in combination or as a single organism in an effort to normalize intestinal microbiota and potentially improve intestinal barrier function. Recent evidence has suggested that inflammatory bowel disease (IBD) may result from an inappropriate immunologic response to intestinal bacteria and a disruption in the balance of the gastrointestinal microbiota in genetically susceptible individuals. Prebiotics, synbiotics, and probiotics have all been studied with growing interest as adjuncts to standard therapies for IBD. In general, probiotics have been shown to be well-tolerated with few side effects, making them a potential attractive treatment option in the management of IBD. Aim To perform a systematic review of randomized controlled trials on the use of probiotics, prebiotics, and synbiotics in IBD. Results In our systematic review we found 14 studies in patients with Crohn’s disease (CD), 21 studies in patients with ulcerative colitis (UC), and five studies in patients with pouchitis. These were randomized controlled trials using probiotics, prebiotics, and/or synbiotics. In patients with CD, multiple studies comparing probiotics and placebo showed no significant difference in clinical outcomes. Adding a probiotic to conventional treatment improved the overall induction of remission rates among patients with UC. There was also a similar benefit in maintaining remission in UC. Probiotics have also shown some efficacy in the treatment of pouchitis after antibiotic-induced remission. Conclusions To date, there is insufficient data to recommend probiotics for use in CD. There is evidence to support the use of probiotics for induction and maintenance of remission in UC and pouchitis. Future quality studies are needed to confirm whether probiotics, prebiotics, and synbiotics have a definite role in induction or maintenance of remission in CD, UC, and pouchitis. Similar to probiotics, fecal microbiota transplantation provides an alternate modality of therapy to treat IBD by influencing the intestinal flora.

Summary Background : Measurement of the hepatic venous pressure gradient may identify a sub-optimal response to drug prophylaxis in patients with a history of variceal bleeding. However, the cost-effectiveness of routine hepatic venous pressure gradient measurements to guide secondary prophylaxis has not been examined. Methods : A Markov model was constructed using specialized software (DATA 3.5, Williamstown, MA, USA). Three strategies involved secondary prophylaxis without haemodynamic monitoring using beta-blockers alone, beta-blockers plus isosorbide mononitrate or endoscopic variceal ligation alone. Four strategies involved secondary prophylaxis with beta-blockers plus isosorbide mononitrate or beta-blockers alone, accompanied by one or two hepatic venous pressure gradient measurements to identify haemodynamic non-responders, who underwent endoscopic variceal ligation as an alternative. The total expected costs, variceal bleeding episodes and total deaths were calculated for each strategy over 3 years. Results : The two most effective strategies were combination therapy alone and combination therapy with two hepatic venous pressure gradient measurements. The incremental cost-effectiveness ratio of the latter strategy was $136 700 per year of life saved compared with combination therapy alone. The ratio improved as the time horizon was extended or the rates of variceal re-bleeding were increased. Conclusions : The cost-effectiveness of haemodynamic monitoring to guide secondary prophylaxis of recurrent variceal bleeding is highly dependent on local hepatic venous pressure gradient measurement costs, life expectancy and re-bleeding rates.

The goal of this study is to evaluate endoscopic Raman spectroscopy as a noninvasive technique to determine histological inflammatory status of colitis. Colon mucosal composition was investigated in vivo from patients with ulcerative colitis (UC) and from age- and body mass index (BMI) matched controls using endoscope-coupled Raman spectroscopy. The results were co-registered with histological assessment of inflammatory status at the same locations. Substantial decreases (50-60%) in the content of phosphotidylcholines (PCs) and total lipids were observed in inflamed colon tissue (histology grade 1, 2 and 3) compared to those from the quiescent (histology grade 0) and from the controls. No significant difference was observed in lipids or PC contents between control and grade 0, or among grades 1 – 3. The degree of lipid unsaturation increased in the inflamed tissue regardless of disease severity. The inflammation-associated alterations in lipids and PC are observed independent of BMI or the anatomical locations for data collection. Multivariate analysis using support vector machine (SVM) algorithm classified the spectra of the controls or the inactive colitis from those of inflamed tissue with a sensitivity of 83.5% and 97.1% respectively. Our results showed that mucosal lipid content is related to the microscopic disease activity, and thus could serve as a valuable spectral marker to differentiate active colitis from the quiescent.