Showing papers in "Clinical and translational gastroenterology in 2019"
TL;DR: The combination of galunisertib and sorafenib showed acceptable safety and a prolonged OS outcome and the pharmacokinetics and safety profiles were consistent with monotherapy of each drug.
Abstract: INTRODUCTION:Inhibition of tumor growth factor-β (TGF-β) receptor type I potentiated the activity of sorafenib in preclinical models of hepatocellular carcinoma (HCC) Galunisertib is a small-molecule selective inhibitor of TGF-β1 receptor type I, which demonstrated activity in a phase 2 trial as se
113 citations
TL;DR: Artificial intelligence via deep learning algorithm may be a more accurate and objective method to diagnose malignancies of IPMNs in comparison to human diagnosis and conventional EUS features.
Abstract: OBJECTIVES:Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic adenocarcinoma. Artificial intelligence (AI) is a mathematical concept whose implementation automates learning and recognizing data patterns. The aim of this study was to investigate whether AI via deep l
101 citations
TL;DR: ATI performed better than CAP, and this improvement was statistically significant for S > 1 (P = 0.04), showing that, in patients with no fibrosis/mild fibrosis, ATI is a very promising tool for the noninvasive assessment of steatosis.
Abstract: OBJECTIVES:The primary aim of this study was to investigate the value of attenuation imaging (ATI), a novel ultrasound technique for detection of steatosis, by comparing the results to that obtained with controlled attenuation parameter (CAP) and by using MRI-derived proton density fat fraction (PDF
88 citations
TL;DR: Altered gut microbiota exist in patients with IBS and have significant association with the development of IBS, according to a systematic review of case–control studies published until February 28, 2018.
Abstract: Introduction Alterations of gut microbiota have been thought to be associated with irritable bowel syndrome (IBS). Many studies have reported significant alterations of gut microbiota in patients with IBS based on 16S ribosomal RNA-targeted sequencing. However, results from these studies are inconsistent or even contradictory. We performed a systematic review to explore the alterations of gut microbiota in patients with IBS compared with healthy controls (HCs). Methods The databases PubMed, Cochrane Library, Web of Science, and Embase were searched for studies published until February 28, 2018, for case-control studies detecting gut microbiota in patients with IBS. Methodological quality was assessed using the Newcastle-Ottawa Scale. The α-diversity and alterations of gut microbiota in patients with IBS compared with HCs were analyzed. Results Sixteen articles involving 777 patients with IBS and 461 HCs were included. Quality assessment scores of the studies ranged from 5 to 7. For most studies, patients with IBS had a lower α-diversity than HCs in both fecal and mucosal samples. Relatively consistent changes in fecal microbiota for patients with IBS included increased Firmicutes, decreased Bacteroidetes, and increased Firmicutes:Bacteroidetes ratio at the phylum level, as well as increased Clostridia and Clostridiales, decreased Bacteroidia and Bacteroidales at lower taxonomic levels. Results for mucosal microbiota were inconsistent. Conclusions Alterations of gut microbiota exist in patients with IBS and have significant association with the development of IBS. Further studies are needed to draw conclusions about gut microbiota changes in patients with IBS. Translational impact This knowledge might improve the understanding of microbial signatures in patients with IBS and would guide future therapeutic strategies.
83 citations
TL;DR: The SIBO landscape is poised for transformation through improved awareness and scientific rigor, and limited numbers of controlled studies have shown systemic antibiotics to be efficacious.
Abstract: Small intestinal bacterial overgrowth (SIBO) is a common, yet underrecognized, problem. Its prevalence is unknown because SIBO requires diagnostic testing. Although abdominal bloating, gas, distension, and diarrhea are common symptoms, they do not predict positive diagnosis. Predisposing factors include proton-pump inhibitors, opioids, gastric bypass, colectomy, and dysmotility. Small bowel aspirate/culture with growth of 10-10 cfu/mL is generally accepted as the "best diagnostic method," but it is invasive. Glucose or lactulose breath testing is noninvasive but an indirect method that requires further standardization and validation for SIBO. Treatment, usually with antibiotics, aims to provide symptom relief through eradication of bacteria in the small intestine. Limited numbers of controlled studies have shown systemic antibiotics (norfloxacin and metronidazole) to be efficacious. However, 15 studies have shown rifaximin, a nonsystemic antibiotic, to be effective against SIBO and well tolerated. Through improved awareness and scientific rigor, the SIBO landscape is poised for transformation.
80 citations
TL;DR: It is demonstrated for the first time that sarcopenia is related to ACLF development and systemic inflammation and the prognostic value of TPMT/height can be improved by using sex-specific cutoffs.
Abstract: INTRODUCTION:Muscle mass has been shown to be a prognostic marker in patients with liver cirrhosis. Transversal psoas muscle thickness normalized by height (TPMT/height) obtained by routine computed tomography is a simple surrogate parameter for sarcopenia. TPMT/height, however, is not sex specific,
75 citations
TL;DR: It is suggested that bowel cleansing prior to the colonoscopy and/or processing of the fecal material as part of the FMT routine contribute to symptoms and gut microbiota composition changes in IBS.
Abstract: Fecal microbiota transfer (FMT) aims at introducing a new gut microbiota to the gastrointestinal system of a patient. It is found to be a safe, highly successful treatment in recurrent Clostridium difficile infection with cure rates of 90% and higher (1,2). Also, other diseases in which the gut microbiota plays a role became of interest for treatment with FMT. Placebo-controlled clinical studies in inflammatory bowel disease have shown that FMT leads to remission in 24%–30% of patients with ulcerative colitis (3–5). Similarly, studies in metabolic syndrome have shown that healthy donor FMT can improve insulin sensitivity (6,7). Due to the increasing evidence that a disturbed gut microbiota also plays a role in the pathophysiology of irritable bowel syndrome (IBS), FMT has been suggested as a potential treatment to improve symptoms in this study population. A recent randomized placebo-controlled clinical trial has studied the effect of FMT administered by colonoscopy on symptoms in 90 patients with IBS (8). More patients in the treatment group (65%) showed a decrease in IBS-severity scoring system (IBS-SSS) score of more than 75 points compared with the placebo group (43%) after 3 months; however, this was not significant anymore after 12 months (56% vs 36%). In an additional recent randomized clinical trial, the effect of FMT administered by capsules in 52 IBS patients was investigated. Although intake of the capsules over 12 days resulted in changes to the gut microbiota of the IBS patients in the treatment group, the symptom improvement after 3 months was larger in the placebo compared with the treatment group (9).
Nowadays, typical characteristics of a healthy gut microbiota are still not known. In IBS patients, butyrate-producing bacteria in fecal samples seem to be reduced compared with healthy subjects (10). Butyrate is a short-chain fatty acid produced in the large intestine by microbial fermentation of undigested dietary carbohydrates. It is the main energy source for colonocytes and has shown to have anti-inflammatory, anticarcinogenic and barrier-protecting properties (11). Butyrate enemas have shown to decrease visceral sensitivity in healthy volunteers and might decrease inflammation in inflammatory bowel disease (12,13). Previous studies demonstrated that the amount of butyrate-producing bacteria could be increased by FMT (7). Here, we describe the outcome of a controlled study investigating FMT in IBS, in which we included donors with a high abundance of butyrate-producing bacteria in their fecal samples and IBS patients with a low abundance of butyrate-producing bacteria. Apart from studying the effect of FMT on the symptoms of IBS patients, also its effect on the patients' visceral sensitivity and on the compositional changes in fecal and mucosa-adherent microbiota were assessed in order to propose mechanistic explanations for the observed responses.
66 citations
TL;DR: Economic burden of hospitalized patients with cirrhosis is increasing with more admissions and longer LOS in DC and CC groups, with important drivers include procedures and portal hypertensive and nonportal hypertensive complications.
Abstract: INTRODUCTION:The prevalence of cirrhosis is increasing despite advances in therapeutics, and it remains an expensive medical condition. Studies examining the healthcare burden of inpatient cirrhosis-related care regardless of etiology, stage, or severity are lacking. This study aims to describe the
60 citations
TL;DR: The revised TIGAR-O_V2 system is designed as a hierarchical checklist for health care workers to quickly document and track specific factors that, alone or in combinations, may contribute to progressive pancreatic disease in individual patients or groups of patients and to assist in treatment selection.
Abstract: The Toxic-metabolic, Idiopathic, Genetic, Autoimmune, Recurrent and severe acute pancreatitis and Obstructive (TIGAR-O) Pancreatitis Risk/Etiology Checklist (TIGAR-O_V1) is a broad classification system that lists the major risk factors and etiologies of recurrent acute pancreatitis, chronic pancreatitis, and overlapping pancreatic disorders with or without genetic, immunologic, metabolic, nutritional, neurologic, metaplastic, or other features. New discoveries and progressive concepts since the 2001 TIGAR-O list relevant to understanding and managing complex pancreatic disorders require an update to TIGAR-O_V2 with both a short (S) and long (L) form. The revised system is designed as a hierarchical checklist for health care workers to quickly document and track specific factors that, alone or in combinations, may contribute to progressive pancreatic disease in individual patients or groups of patients and to assist in treatment selection. The rationale and key clinical considerations are summarized for each updated classification item. Familiarity with the structured format speeds up the completion process and supports thoroughness and consideration of complex or alternative diagnoses during evaluation and serves as a framework for communication. The structured approach also facilitates the new health information technologies that required high-quality data for accurate precision medicine. A use primer accompanies the TIGAR-O_V2 checklist with rationale and comments for health care workers and industries caring for patients with pancreatic diseases.
59 citations
TL;DR: In this pilot study, convolutional neural network using multiple archived gastric images achieved high diagnostic accuracy for the evaluation of H. pylori infection.
Abstract: Objectives Application of artificial intelligence in gastrointestinal endoscopy is increasing. The aim of the study was to examine the accuracy of convolutional neural network (CNN) using endoscopic images for evaluating Helicobacter pylori (H. pylori) infection. Methods Patients who received upper endoscopy and gastric biopsies at Sir Run Run Shaw Hospital (January 2015-June 2015) were retrospectively searched. A novel Computer-Aided Decision Support System that incorporates CNN model (ResNet-50) based on endoscopic gastric images was developed to evaluate for H. pylori infection. Diagnostic accuracy was evaluated in an independent validation cohort. H. pylori infection was defined by the presence of H. pylori on immunohistochemistry testing on gastric biopsies and/or a positive 13C-urea breath test. Results Of 1,959 patients, 1,507 (77%) including 847 (56%) with H. pylori infection (11,729 gastric images) were assigned to the derivation cohort, and 452 (23%) including 310 (69%) with H. pylori infection (3,755 images) were assigned to the validation cohort. The area under the curve for a single gastric image was 0.93 (95% confidence interval [CI] 0.92-0.94) with sensitivity, specificity, and accuracy of 81.4% (95% CI 79.8%-82.9%), 90.1% (95% CI 88.4%-91.7%), and 84.5% (95% CI 83.3%-85.7%), respectively, using an optimal cutoff value of 0.3. Area under the curve for multiple gastric images (8.3 ± 3.3) per patient was 0.97 (95% CI 0.96-0.99) with sensitivity, specificity, and accuracy of 91.6% (95% CI 88.0%-94.4%), 98.6% (95% CI 95.0%-99.8%), and 93.8% (95% CI 91.2%-95.8%), respectively, using an optimal cutoff value of 0.4. Discussion In this pilot study, CNN using multiple archived gastric images achieved high diagnostic accuracy for the evaluation of H. pylori infection.
58 citations
TL;DR: A signature of 6 miRNAs are identified and validated as predictors that can differentiate significantly patients with CRC and AA from those who are healthy, however, large-scale validation studies in asymptomatic screening participants should be conducted.
Abstract: OBJECTIVES: Specific microRNA (miRNA) signatures in biological fluids can facilitate earlier detection of the tumors being then minimally invasive diagnostic biomarkers. Circulating miRNAs have also emerged as promising diagnostic biomarkers for colorectal cancer (CRC) screening. In this study, we investigated the performance of a specific signature of miRNA in plasma samples to design a robust predictive model that can distinguish healthy individuals from those with CRC or advanced adenomas (AA) diseases. METHODS: Case control study of 297 patients from 8 Spanish centers including 100 healthy individuals, 101 diagnosed with AA, and 96 CRC cases. Quantitative real-time reverse transcription was used to quantify a signature of miRNA (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) in plasma samples. Binary classifiers (Support Vector Machine [SVM] linear, SVM radial, and SVM polynomial) were built for the best predictive model. RESULTS: Area under receiving operating characteristic curve of 0.92 (95% confidence interval 0.871-0.962) was obtained retrieving a model with a sensitivity of 0.85 and specificity of 0.90, positive predictive value of 0.94, and negative predictive value of 0.76 when advanced neoplasms (CRC and AA) were compared with healthy individuals. CONCLUSIONS: We identified and validated a signature of 6 miRNAs (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) as predictors that can differentiate significantly patients with CRC and AA from those who are healthy. However, large-scale validation studies in asymptomatic screening participants should be conducted.
TL;DR: The study provides the evidence that PSMA is specifically expressed in tumor-associated vasculature of HCC, and vascular PSMA expression may be used as a novel prognostic marker and a vascular therapeutic target for HCC.
Abstract: INTRODUCTION:Prostate-specific membrane antigen (PSMA) was originally found to be specifically expressed in normal prostate, and its expression was upregulated in almost all stages of prostate cancer. In recent years, PSMA was also found to be expressed in tumor-associated vasculature in many nonpro
TL;DR: Novel signatures combining miRNAs and CA19.9 could be used as noninvasive biomarkers for early detection of PDAC.
Abstract: OBJECTIVES:Pancreatic ductal adenocarcinoma (PDAC) presents the lowest survival rate of all cancers because only 6% of patients reach five-year survival. Alterations in the expression of several microRNAs (miRNAs) occur in the tumor of PDAC and in preneoplastic lesions as the called intraductal papi
TL;DR: This primer demonstrates the contrasting strengths and limitations of each paradigm and why precision medicine will eventually deliver on the promises.
Abstract: Precision medicine promises patients with complex disorders the right treatment for the right patient at the right dose at the right time with expectation of better health at a lower cost. The demand for precision medicine highlights the limitations of modern Western medicine. Modern Western medicine is a population-based, top-down approach that uses pathology to define disease. Precision medicine is a bottom-up approach that identifies predisease disorders using genetics, biomarkers, and modeling to prevent disease. This primer demonstrates the contrasting strengths and limitations of each paradigm and why precision medicine will eventually deliver on the promises.
TL;DR: Circulating and tissue-activated Tfh cells are expanded in IgG 4-SC/AIP, correlate with disease activity, and can drive class switch and proliferation of IgG4-committed B cells.
Abstract: OBJECTIVES:Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) and autoimmune pancreatitis (AIP) are characterized by an abundance of circulating and tissue IgG4-positive plasma cells. T-follicular helper (Tfh) cells are necessary for B-cell differentiation into plasma cells. We aimed at elucidating the presence and phenotype of Tfh cells and their relationship with disease activity in IgG4-SC/AIP. METHODS:Circulating Tfh-cell subsets were characterized by multiparametric flow cytometry in IgG4-SC/AIP (n = 18), disease controls with primary sclerosing cholangitis (n = 8), and healthy controls (HCs, n = 9). Tissue Tfh cells were characterized in IgG4-SC/AIP (n = 12) and disease control (n = 10) specimens. Activated PD1+ Tfh cells were cocultured with CD27+ memory B cells to assess their capacity to support B-cell differentiation. Disease activity was assessed using the IgG4-responder index and clinical parameters. RESULTS:Activated circulating PD-1+CXCR5+ Tfh cells were expanded in active vs inactive IgG4-SC/AIP, primary sclerosing cholangitis, and HC (P < 0.01), with enhanced PD-1 expression on all Tfh-cell subsets (Tfh1, P = 0.003; Tfh2, P = 0.0006; Th17, P = 0.003). Expansion of CD27+CD38+CD19lo plasmablasts in active disease vs HC (P = 0.01) correlated with the PD-1+ Tfh2 subset (r = 0.69, P = 0.03). Increased IL-4 and IL-21 cytokine production from stimulated cells of IgG4-SC/AIP, important in IgG4 class switch and proliferation, correlated with PD-1+ Tfh2 (r = 0.89, P = 0.02) and PD-1+ Tfh17 (r = 0.83, P = 0.03) subsets. Coculture of PD1+ Tfh with CD27+ B cells induced higher IgG4 expression than with PD1- Tfh (P = 0.008). PD-1+ Tfh2 cells were strongly associated with clinical markers of disease activity: sIgG4 (r = 0.70, P = 0.002), sIgE (r = 0.66, P = 0.006), and IgG4-responder index (r = 0.60, P = 0.006). Activated CXCR5+ Tfh cells homed to lymphoid follicles in IgG4-SC/AIP tissues. CONCLUSIONS:Circulating and tissue-activated Tfh cells are expanded in IgG4-SC/AIP, correlate with disease activity, and can drive class switch and proliferation of IgG4-committed B cells. PD1+ Tfh2 cells may be a biomarker of active disease and a potential target for immunotherapy.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Cedars-Sinai Medical Center1, University of Pittsburgh2, Los Angeles Biomedical Research Institute3, University of Minnesota4, Saint Louis University5, Virginia Commonwealth University6, Brigham and Women's Hospital7, The Ohio State University Wexner Medical Center8, Medical University of South Carolina9, University of Florida10, Dartmouth–Hitchcock Medical Center11, Baptist Memorial Hospital-Memphis12, Mayo Clinic13, Yale University14, St Mary's Hospital15, Indiana University – Purdue University Indianapolis16, Johns Hopkins University17, University of Alabama at Birmingham18, Stanford University19, National Institutes of Health20
TL;DR: The study suggests that CP-DM may be a subtype of T2DM, a notion that should be tested in future, large prospective studies.
Abstract: Introduction:Diabetes mellitus (DM) is a complication of chronic pancreatitis (CP). Whether pancreatogenic diabetes associated with CP-DM represents a discrete pathophysiologic entity from type 2 DM (T2DM) remains uncertain. Addressing this question is needed for development of specific measures to
TL;DR: CC is associated with a specific fecal microbiome seen primarily in patients with active disease or ongoing corticosteroid treatment, whereas the microbiome of CC patients in remission resembled that of healthy controls and the shift in key taxa, including the Ruminococcaceae family, was observed in IBD.
Abstract: INTRODUCTION:In inflammatory bowel disease (IBD), an aberrant immune response to gut microbiota is important, but the role of the microbiota in collagenous colitis (CC) is largely unknown. We aimed to characterize the microbiota of patients with CC compared with that of healthy control and patients
TL;DR: Within the AYA population, colorectal cancers differ by clinicopathologic and racial/ethnic characteristics that partially underlie age- and race-related differences in cancer susceptibility and outcomes.
Abstract: Objectives Despite overall reductions in colorectal cancer burden, incidence rates continue to rise among younger patients, and causes remain unknown. We examined differences in clinicopathologic and racial/ethnic characteristics within the adolescent and young adult (AYA) population diagnosed with colorectal cancer in the United States. Methods Using the National Cancer Institute's Surveillance, Epidemiology, and End Results program data, we identified individuals diagnosed with first primary colorectal cancer between ages 15 and 39 years from 2010 to 2015. Adjusted multivariable logistic regression models were used to quantify clinicopathologic and racial/ethnic differences across age at onset subgroups (15-19, 20-24, 25-29, 30-34, and 35-39 years). Results We identified 5,350 AYA patients diagnosed with colorectal cancer. Of note, 28.6% of AYA cases were diagnosed with right-sided tumors (cecum to transverse colon). The proportion of right-sided colorectal cancers differed significantly by age group at diagnosis (38.3% vs 27.3% of AYAs aged 15-19 vs 35-39 years, respectively; P trend = 0.01). Proportions of cases with mucinous adenocarcinoma and signet ring cell carcinoma histopathologic subtypes significantly increased with younger age at onset (P trends = 0.01 and 0.03, respectively). Differences in clinical stage were observed across AYA age groups, with stage II disease increasing with younger age (P trend = 0.01). The proportion of Hispanic AYAs was higher within younger patients, accounting for 21.0% of the AYA population aged 35-39 years up to 28.3% of 15-19-year-old individuals (P trend = 0.003). Discussion Within the AYA population, colorectal cancers differ by clinicopathologic and racial/ethnic characteristics. Further investigation of the clinical and biologic diversity of colorectal cancers that partially underlie age- and race-related differences in cancer susceptibility and outcomes is warranted.
TL;DR: The introduction of next-generation sequencing facilitates a more comprehensive annotation of intertumor heterogeneity, resulting in more sensitive and accurate clonal discrimination, and Immunotherapy that inhibits immune checkpoint interaction may be an optimal choice for both MO- and IM-HCC.
Abstract: Hepatocellular carcinoma (HCC) is characterized by high prevalence of multifocality. Multifocal HCC can arise synchronously or metachronously either from intrahepatic metastasis (IM) or multicentric occurrence (MO). To date, there have been no established criteria to accurately distinguish whether multifocal HCC originates from IM or MO. Histopathological features remain the most convenient strategy but with subjectivity and limited accuracy. Various molecular biological techniques involving assessment of TP53 mutation status, hepatitis B virus integration sites, and chromosomal alterations have been applied to determine the clonal origin. The introduction of next-generation sequencing facilitates a more comprehensive annotation of intertumor heterogeneity, resulting in more sensitive and accurate clonal discrimination. Generally, MO-HCC has better overall survival than IM-HCC after curative resection. Adjuvant antiviral treatment has been proved to decrease post-treatment recurrence probably by reducing MO-HCC recurrence, whereas adjuvant sorafenib treatment targeting prior micrometastasis failed to reduce IM-HCC recurrence. Recent studies recommended transcatheter arterial chemoembolization (TACE) and traditional Chinese medicine Huaier granule as effective adjuvant treatments probably by preventing IM and both types of recurrences respectively. Immunotherapy that inhibits immune checkpoint interaction may be an optimal choice for both MO- and IM-HCC. In the future, effective personalized therapy against multifocal HCC may be achieved.
TL;DR: The results suggest that the frequency of intratumoral PD-1high CD8+ T cells may serve as a biomarker to identify which individuals will benefit from which treatment and support the use of combination strategies.
Abstract: INTRODUCTION:Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Today, a promising treatment strategy is focused on the enhancement of antitumor immune responses by immune checkpoint modification. However, as only 20% of patients with HCC are responders, i
TL;DR: Studies to parse the underlying contributions of the gut microbiota to metabolic sequelae of pancreatitis will offer important translational insights with a view to preventing exocrine pancreatic dysfunction and new-onset diabetes after pancreatitis.
Abstract: Pancreatitis, a complex disease influenced by both genetic and environmental factors, often leads to metabolic sequelae (such as exocrine pancreatic dysfunction and new-onset diabetes). Several trillion micro-organisms inhabit the gastrointestinal tract, and this community plays an important role in the regulation of functions of not only the gut but also the pancreas. Studies to parse the underlying contributions of the gut microbiota to metabolic sequelae of pancreatitis will offer important translational insights with a view to preventing exocrine pancreatic dysfunction and new-onset diabetes after pancreatitis.
TL;DR: A blood-based CTC platform demonstrated high sensitivity in detecting adenomas and CRC, as well as reasonable specificity in an enriched symptomatic patient population, which has the potential to prevent CRC by improving patient compliance and detecting precancerousAdenomas, eventually reducing CRC mortality.
Abstract: OBJECTIVES:There is a significant unmet need for a blood test with adequate sensitivity to detect colorectal cancer (CRC) and adenomas. We describe a novel circulating tumor cell (CTC) platform to capture colorectal epithelial cells associated with CRC and adenomas.METHODS:Blood was collected from 6
TL;DR: SIBO complicates 38% of CP with OR of 5.58 indicating a predisposition for this condition, and PEI correlates with SIBO in CP and might play a role in pathophysiology.
Abstract: Chronic pancreatitis (CP) is an inflammatory disorder involving injury and scarring of the pancreatic exocrine gland, which can also affect endocrine components. It has a global incidence of 10 per 100,000 population (1). CP results in a variety of signs and symptoms, including abdominal pain, weight loss, bloating, steatorrhea, malabsorption, and diarrhea. CP complications include pancreatic exocrine insufficiency (PEI), postpancreatitis diabetes mellitus (DM), and pancreatic cancer. Management of CP is challenging with multiple modalities targeting symptoms and malnutrition through pain management, pancreatic enzyme replacement therapy (PERT), and, in severe cases, surgery including total pancreatectomy. Despite advancements in CP treatment, 43% of patients do not respond to conventional therapy (2).
Recent evidence suggests that pancreatic exocrine dysfunction is a major determinant of intestinal microbiota (3). Changes in the gut microbial composition have been linked to a wide array of disorders spanning infectious (4), autoimmune (5), functional (6), neoplastic (7), and gastrointestinal (GI) pathologies. Multiple reports have linked CP to microbial dysbiosis, mainly small intestinal bacterial overgrowth (SIBO). SIBO has classically been linked to blind-loop–producing GI surgeries; the resulting combination of altered anatomy, altered motility, hypochlorhydria, and exposure to colonic contents creates a favorable environment for bacterial proliferation (8). SIBO is associated with inflammatory bowel disease (9,10), neurological disorders (11,12), celiac disease (13), and irritable bowel syndrome (14). SIBO symptoms include abdominal pain, bloating, diarrhea, and malabsorption, which overlap with CP and make the diagnosis and management of SIBO in CP all the more difficult. Although Capurso et al. (15) showed in 2016 that SIBO affects 36% of patients with CP, we noted a high level of heterogeneity in the reported SIBO prevalence. In addition, their review lacked an analysis of SIBO's response to treatment or of risk factors for SIBO in CP. Moreover, we found that 3 additional studies (16–18) had been published on this subject since then. Therefore, we performed a comprehensive systematic review and meta-analysis employing rigorous statistical analysis using meta-regression models to explain heterogeneity, determine factors affecting disease prevalence, and response to treatment of SIBO in CP.
TL;DR: It is did not confirm that anti-CdtB/anti-vinculin discriminated IBS diarrhea from organic GI disease in Australian subjects, but it did find higher anti- CdtB in FD and IBS/FD overlap vs healthy controls.
Abstract: OBJECTIVES: Anti-cytolethal distending toxin B (CdtB) and anti-vinculin antibodies have been proposed as biomarkers that discriminate irritable bowel syndrome (IBS) diarrhea from inflammatory bowel disease; however, it is unknown whether they can also discriminate patients with IBS and IBS subtypes and functional dyspepsia (FD) from healthy individuals in the general population. We aimed to determine whether anti-CdtB and anti-vinculin can discriminate IBS and FD from health and from organic gastrointestinal (GI) disease.METHODS: Adults were enrolled from 2 Australian studies: (i) a random, population-based study (n = 331) with subjects diagnosed with IBS (n = 63) or FD (n = 61) by modified Rome III criteria or healthy control subjects (n = 246) who did not meet criteria for IBS and/or FD and (ii) an outpatient-based study with subjects diagnosed with IBS (n = 256) and/or FD (n = 55) or organic GI disease (n = 182) by an independent clinician. Serum levels of anti-CdtB/anti-vinculin antibodies were determined by enzyme-linked immunosorbent assay.RESULTS: There was a significantly higher mean value of anti-CdtB in FD vs healthy controls (mean = 2.46 [SD = 0.72] vs mean = 2.14 [SD = 0.771; P = 0.005) and IBS/FD overlap vs healthy controls (mean = 2.47 [SD = 0.78] vs mean = 2.14 [SD = 0.77] ; P = 0.02). There were no significant differences in anti-CdtB in IBS and FD outpatients or IBS/FD subgroups compared with patients with organic GI disease. In terms of anti-vinculin, there were no significant differences between IBS and FD and healthy controls or between IBS and FD and organic GI disease controls.DISCUSSION: We did not confirm that anti-CdtB/anti-vinculin discriminated IBS diarrhea from organic GI disease in Australian subjects. However, we did find higher anti-CdtB in FD and IBS/FD overlap vs healthy controls. Postinfectious FD may be more common than currently recognized.
TL;DR: Findings indicate that perturbations in the salivary microbiome may have a role in EoE pathobiology and could serve as a noninvasive marker of disease activity.
Abstract: OBJECTIVES:Eosinophilic esophagitis (EoE) is an allergen-mediated inflammatory disease affecting the esophagus. Although microbial communities may affect the host immune responses, little is known about the role of the microbiome in EoE. We compared the composition of the salivary microbiome in chil
TL;DR: There is no significant difference in results between M and XL probes when they are used in the right conditions, and in clinical practice, the probe should be selected according to the BMI and the Automatic Probe Selection tool.
Abstract: INTRODUCTION:FibroScan's M and XL probes give significantly different results, which could lead to misevaluation of liver fibrosis if the correct probe is not chosen. According to the manufacturer, the M probe should be used when the skin–liver capsule distance (SCD) is <25 mm, and the XL probe shou
TL;DR: It was shown that HDC had a reduction of blood MAIT cells despite showing little evidence of immune activation, whereas patients with AH had a severe depletion of bloodMAIT cells and the residual cells were highly activated.
Abstract: Objectives Alcoholic hepatitis (AH) develops in approximately 30% of chronic heavy drinkers. The immune system of patients with AH is hyperactivated, yet ineffective against infectious diseases. Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are highly enriched in liver, mucosa, and peripheral blood and contribute to antimicrobial immunity. We aimed to determine whether MAIT cells were dysregulated in heavy drinkers with and without AH and the effects of alcohol abstinence on MAIT cell recovery. Methods MR1 tetramers loaded with a potent MAIT cell ligand 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil were used in multiparameter flow cytometry to analyze peripheral blood MAIT cells in 59 healthy controls (HC), 56 patients with AH, and 45 heavy drinkers without overt liver disease (HDC) at baseline and 6- and 12-month follow-ups. Multiplex immunoassays were used to quantify plasma levels of cytokines related to MAIT cell activation. Kinetic Turbidimetric Limulus Amebocyte Lysate Assay and ELISA were performed to measure circulating levels of 2 surrogate markers for bacterial translocation (lipopolysaccharide and CD14), respectively. Results At baseline, patients with AH had a significantly lower frequency of MAIT cells than HDC and HC. HDC also had less MAIT cells than HC (median 0.16% in AH, 0.56% in HDC, and 1.25% in HC). Further, the residual MAIT cells in patients with AH expressed higher levels of activation markers (CD69, CD38, and human leukocyte antigen [HLA]-DR), the effector molecule granzyme B, and the immune exhaustion molecule PD-1. Plasma levels of lipopolysaccharide and CD14 and several cytokines related to MAIT cell activation were elevated in patients with AH (interferon [IFN]-α, interleukin [IL]-7, IL-15, IL-17, IL-18, IL-23, IFN-γ, and tumor necrosis factor α). Decreased MAIT cell frequency and upregulated CD38, CD69, and HLA-DR correlated negatively and positively, respectively, with aspartate aminotransferase level. MAIT cell frequency negatively correlated with IL-18. HLA-DR and CD38 levels correlated with several cytokines. At follow-ups, abstinent patients with AH had increased MAIT cell frequency and decreased MAIT cell activation. However, MAIT cell frequency was not fully normalized in patients with AH (median 0.31%). Discussion We showed that HDC had a reduction of blood MAIT cells despite showing little evidence of immune activation, whereas patients with AH had a severe depletion of blood MAIT cells and the residual cells were highly activated. Alcohol abstinence partially reversed those abnormalities.
TL;DR: It is suggested that abnormal lipid metabolism associates with the development of clinical CD and occurs already before the first introduction of gluten to the diet, and the specific TGs found elevated in CD progressors may be due to a host response to compromised intake of essential lipids in the small intestine, requiring de novo lipogenesis.
Abstract: OBJECTIVES:Celiac disease (CD) is a chronic enteropathy characterized by an autoimmune reaction in the small intestine of genetically susceptible individuals. The underlying causes of autoimmune reaction and its effect on host metabolism remain largely unknown. Herein, we apply lipidomics to elucida
TL;DR: The study suggests that Fecobionics is safe and effective in evaluation of key defecatory parameters and agreement was found for comparable variables between ARM-BET and FECobionics but not for other variables.
Abstract: INTRODUCTION Defecation is a complex process that can be easily disturbed. Defecatory disorders may be diagnosed using specialized investigation, including anorectal manometry (ARM) and the balloon expulsion test (BET). Recently, we developed a simulated stool named Fecobionics that integrates several tests and assesses pressures, orientation, and bending during evacuation. The aim was to evaluate the feasibility and performance of Fecobionics for assessing defecatory physiology in normal subjects. METHODS Physiological expulsion parameters were assessed in an interventional study design. The 10-cm-long Fecobionics probe contained pressure sensors at the front and rear and inside a bag and 2 motion processor units. The bag was distended in the rectum of 20 presumed normal subjects (15 female/5 male) until urge to defecate. ARM-BET was also performed. Three subjects used +2 minutes to evacuate BET, and 1 subject had a high fecal incontinence score. Therefore, the normal group consisted of 16 subjects (13 female/3 male aged 25-78 years). RESULTS All subjects reported that Fecobionics evacuation was similar to normal defecation. Fecobionics expulsion pressure signatures demonstrated 5 phases, reflecting rectal pressure, anal relaxation, and anal passage. Preload-afterload loop diagrams demonstrated clockwise contraction cycles. The expulsion duration for BET and Fecobionics was 16 ± 2 and 23 ± 5 seconds (P > 0.2), respectively. The duration of the Fecobionics and BET expulsions was associated (P < 0.001). The change in bending of Fecobionics during defecation was 40 ± 3°. DISCUSSION Fecobionics obtained reliable data under physiological conditions. Agreement was found for comparable variables between ARM-BET and Fecobionics but not for other variables. The study suggests that Fecobionics is safe and effective in evaluation of key defecatory parameters.
TL;DR: Poor nutrition increases the risk of infectious complications after surgery and the detrimental effects of poor nutrition on postsurgical infection may be enhanced in patients who have received biologic therapy preoperatively.
Abstract: OBJECTIVES:A case-control study was undertaken to assess the impact of preoperative nutrition on surgical outcomes in patients with inflammatory bowel disease with vs without preoperative biologic therapy.METHODS:Seventy patients who had received biologic therapy within 8 weeks before undergoing res