Microbial translocation across the GI tract.

The lumen of the gastrointestinal (GI) tract is home to an enormous quantity of different bacterial species, our microbiota, that thrive in an often symbiotic relationship with the host. Given that the healthy host must regulate contact between the microbiota and its immune system to avoid overwhelming systemic immune activation, humans have evolved several mechanisms to attenuate systemic microbial translocation (MT) and its consequences. However, several diseases are associated with the failure of one or more of these mechanisms, with consequent immune activation and deleterious effects on health. Here, we discuss the mechanisms underlying MT, diseases associated with MT, and therapeutic interventions that aim to decrease it.

Hepatobiliary Organoids and Their Applications for Studies of Liver Health and Disease: Are We There Yet?

Organoid culture systems have emerged as a frontier technology in liver and biliary research. These three-dimensional (3D) cell cultures derived from pluripotent and adult hepatobiliary cells model organ structure and function. Building on gastrointestinal organoid establishment, hepatobiliary organoid cultures were generated from mouse leucine-rich repeat-containing G-protein-coupled receptor 5-positive liver progenitor cells. Subsequently, 3D hepatobiliary organoid cultures were developed from hepatocytes and cholangiocytes to model human and animal hepatobiliary health and disease. Hepatocyte organoids have been used to study Alagille syndrome, fatty liver disease, Wilson disease, hepatitis B viral infection, and cystic fibrosis. Cholangiocyte organoids have been established to study normal cholangiocyte biology and primary sclerosing cholangitis and to test organoid potential to form bile ducts and gallbladder tissue in vitro. Hepatobiliary cancer organoids, termed tumoroids, have been established from frozen and fresh human tissues and used as a drug-testing platform and for biobanking of cancer samples. CRISPR-based gene modifications and organoid exposure to infectious agents have permitted the generation of organoid models of carcinogenesis. This review summarizes currently available adult cell-derived hepatobiliary organoid models and their applications. Challenges faced by this young technology will be discussed, including the cellular immaturity of organoid-derived hepatocytes, co-culture development to better model complex tissue structure, the imperfection of extracellular matrices, and the absence of standardized protocols and model validation.

Changes in National Google Trends and Local Healthcare Utilization After High-Impact Gastroenterology Publications.

INTRODUCTION: We examined national Google Trends and local healthcare utilization after 3 high-impact gastroenterology publications. METHODS: Changes in US Google Trends and Olmsted County health utilization were studied. RESULTS: Publication views within 30 days were 51,458 (Imperiale), 49,759 (Pimentel), and 18,750 (Gomm). Colonoscopy searches (P = 0.04) and Cologuard tests performed (P < 0.01) increased while colonoscopies decreased (P < 0.01). Searches for rifaximin (P = 0.05), irritable bowel syndrome (P < 0.01), diarrhea (P < 0.01), and rifaximin prescriptions (P = 0.02) increased. Increase in hydrogen-2 blocker searches (P = 0.02) and prescriptions (P < 0.01) and gastroesophageal reflux disease (P < 0.01) and dementia office visits (P < 0.01) occurred. DISCUSSION: High-impact gastroenterology publications influence Google searches and local population-based healthcare utilization.

Comparison of Aerodigestive and Nonaerodigestive Provider Responses to Clinical Case Vignettes.

OBJECTIVE: To evaluate differences in practice patterns between aerodigestive and nonaerodigestive providers in pediatric gastroenterology when diagnosing and treating common aerodigestive complaints. STUDY DESIGN: A questionnaire comprised of clinical vignettes with multiple-choice questions was distributed to both aerodigestive and nonaerodigestive pediatric gastroenterologists. Vignettes focused on management of commonly encountered general gastroenterology and aerodigestive issues, such as gastroesophageal (GE) reflux, aspiration, and feeding difficulties. Tests of equal proportions were used to compare rates of testing and empiric therapy within and across groups. Multivariate analysis was used to assess differences in response rates between aerodigestive and nonaerodigestive providers. RESULTS: A total of 88 pediatric gastroenterologists from 18 institutions completed the questionnaire. There were 35 aerodigestive gastroenterology providers and 53 nonaerodigestive gastroenterology providers. The nonaerodigestive group included 31 general gastroenterologists and 22 providers with self-identified subspecialty gastroenterology expertise. Aerodigestive specialists were more likely than nonaerodigestive gastroenterologists to pursue testing over empiric therapy in cases involving isolated respiratory symptoms (P < .05); aerodigestive providers were more likely to recommend pH-impedance testing, videofluoroscopic swallow studies, and upper gastrointestinal barium study (P < .05 for each test) depending on the referring physician. For vignettes involving infant GE reflux, both groups chose empiric treatments more frequently than testing (P < .001), although aerodigestive providers were more likely than nonaerodigestive providers to pursue testing like upper gastrointestinal barium studies (P < .05). CONCLUSIONS: Although some practice patterns were similar between groups, aerodigestive providers pursued more testing than nonaerodigestive providers in several clinical scenarios including infants with respiratory symptoms and GE reflux.

Modulating host gene expression via gut microbiome-microRNA interplay to treat human diseases.

The human gastrointestinal (GI) tract hosts trillions of microbial inhabitants involved in maintaining intestinal homeostasis, dysbiosis of which provokes a motley of pathogenic and autoimmune disorders. While the mechanisms by which the microbiota modulates human health are manifold, their liberated metabolites from ingested dietary supplements play a crucial role by bidirectionally regulating the expression of micro-ribonucleic acids (miRNAs). miRNAs are small endogenous non-coding RNAs (ncRNAs) that have been confirmed to be involved in an interplay with microbiota to regulate host gene expression. This comprehensive review focuses on key principles of miRNAs, their regulation, and crosstalk with gut microbiota to influence host gene expression in various human disorders, by bringing together important recent findings centric around miRNA-microbiota interactions in diseases along various axis of the gut with other organs. We also attempt to lay emphasis on exploiting the avenues of gut-directed miRNA therapeutics using rudimentary dietary supplements to regulate abnormal host gene expression in diseases, opening doors to an accessible and economical therapeutic strategy.

Effects of coronavirus disease 2019 on the digestive system and its nutritional implications.

PURPOSE OF REVIEW: There has been a deluge of scientific data since coronavirus disease 2019 (COVID-19) was first reported. The effects of COVID-19 on the digestive system are now increasingly well understood. This article aims to review the current data on the effects of COVID-19 on the digestive system with particular emphasis on preexisting digestive diseases and its implications on nutrition practices. RECENT FINDINGS: Evidence has shown that Severe acute respiratory syndrome coronavirus 2 virus affects the gastrointestinal (GI) tract, pancreas and hepatobiliary system resulting in different GI manifestations. Several preexisting digestive diseases have been investigated. These studies have revealed that these special patient population groups are generally not at an increased risk to contract COVID-19, but are susceptible to develop increasing severity of disease. Aside from medical therapy, optimizing nutritional care has a beneficial role in this group of patients. SUMMARY: GI manifestations of COVID-19 in addition to preexisting digestive diseases have an impact on patient's nutrition. Digestion, absorption and transport of nutrients may be impaired. To date, there are no existing guidelines on the nutritional management of patients for this particular at-risk group. Most nutrition practices are based only on observations and clinical experience. Basic prepandemic nutrition care principles are primarily followed but often individualized based on clinical judgment.

Clinical profiles and diagnostic challenges in 1158 children with rare hepatobiliary disorders.

BACKGROUND: Diagnosis of rare diseases possesses a great challenge in pediatric hepatology because expert knowledge in the field is extremely insufficient. The study aims to explore new findings and collect diagnostic experience from pediatric rare liver diseases. METHODS: The large-sample case analysis study included pediatric patients who had liver-involved rare diseases. All cases underwent liver biopsy and/or gene sequencing. RESULTS: A total of 1158 pediatric patients were identified. Liver-based genetic diseases were most frequent (737 cases), followed by liver damages involved in extrahepatic or systemic disorders (151 cases) and cryptogenic hepatobilliary abnormalities (123 cases). Of note, diagnoses of 16 patients were re-evaluated according to genetic results combined with clinical pointers. In addition, 101 patients who underwent gene sequencing remained undiagnosed. Of them, 55 had negative genetic findings, 30 harbored mutations that failed to meet their typically pathogenic condition, and 16 had detected variants that were inconsistent with clinical pointers. CONCLUSIONS: As a study involving known largest number of children with rare hepatobiliary disorders, it allows us to accumulate information (especially new findings) on the etiology and diagnosis of these disorders. The results can help to improve the diagnostic quality in the population. IMPACT: Liver-based genetic diseases were most frequent in clinical profiles of pediatric rare liver diseases. Some novel variants in cases with genetic diseases (for example, two variants of c.3638G>T and c.1435G>C in a patient with progressive familial intrahepatic cholestasis type 2) were identified. As a study involving known largest number of pediatric cases with rare hepatobiliary disorders, it allows us to accumulate information on the etiology and diagnosis of these disorders. The study can help to optimize the diagnostic process and significantly improve the diagnostic quality in the field of pediatric hepatology. Given that clinical variability often exists within rare genetic disease entities and not all rare disorders are genetic, clinicians should not over-depend on the genetic results in the diagnosis.

Double Guidewire Technique Using an Uneven Double Lumen Catheter for Endoscopic Ultrasound-Guided Interventions.

BACKGROUND: Endoscopic ultrasonography (EUS)-guided interventions are often performed using a single guidewire (SGW), but there are a few reports on the use of double guidewire (DGW) technique to facilitate multiple drainage placement during EUS-guided drainage of pancreatic fluid collections. This DGW technique may have advantages other than multiple drainage placement during EUS-guided interventions such as scope stabilization, support for stone extraction and device insertion. METHODS: Consecutive patients who underwent EUS-guided interventions between Feb 2012 and Apr 2019 were retrospectively reviewed. The rate and reasons of DGW technique, and clinical outcomes were evaluated. DGW technique was performed, using an uneven double lumen cannula (UDLC), which facilitates insertion of 0.025-in. and 0.035-in. guidewires. RESULTS: A total of 249 EUS-guided interventions were analyzed, and DGW technique was utilized primarily in 65 cases (25.7%) and as a salvage after failed SGW technique in 18 cases (7.1%). The reasons for DGW technique were 60 multiple drainage placement, 10 scope stabilization, 7 device insertion, 5 safety guidewire, and 4 antegrade stone removal. Insertion of UDLC and DGW was successful in 100%. Technical success rate of preplanned interventions was 92.7% (96.9% in primary DGW and 77.8% in salvage DGW technique). Adverse events were observed in 19.5% after DGW but were not related to DGW technique. CONCLUSIONS: DGW technique using UDLC during EUS-guided interventions was technically feasible and safe. In addition to multiple drainage insertion, it can potentially support complex EUS-guided interventions.

The Way to Man's Heart Is through the Stomach.

Organ systems do not exist in a vacuum. However, in an era of increasingly specialized medicine, the focus is often on the organ system alone. Many symptoms are associated with differential diagnoses from upper gastrointestinal (GI) and cardiovascular medical and surgical specialties. Furthermore, a large number of rare but deadly conditions cross paths between the upper GI tract and cardiovascular system; a significant proportion of these are iatrogenic injuries from a parallel specialty. These include unusual fistulae, herniae, and embolisms that transcend specialties. This review highlights these conditions and the shared anatomy and embryology of the two organ systems.

A nationwide population-based study on therapeutic plasma exchange for 10 years in Korea using Health Insurance Review and Assessment database.

INTRODUCTION: Indications for therapeutic plasma exchange (TPE) have expanded over the years, and the number of procedures is expected to have been increased. Apheresis registries can be difficult to sustain due to workload and privacy issues. This study aimed to analyze national claims data to characterize the use of TPE. MATERIALS AND METHODS: Patients who underwent TPE were retrospectively identified between January 2008 and December 2017 from the Korean Health Insurance Review and Assessment Service database. Data of patients' characteristics, primary diagnosis, hospitalization, treatment, and procedures were analyzed. RESULTS: A total of 9944 patients underwent 62 606 TPE procedures. The median number of TPE procedures performed per patient was 5 (interquartile range, 3-7). Fresh frozen plasma (71.4%) was most commonly used as the replacement fluid. The most common indication was renal diseases (36.8%), followed by hepato-biliary (17.6%) and hematological (15.2%) diseases. Increased frequency of renal diseases was the most remarkable change, which increased from 529 (21.2%) procedures in 2008 to 4107 (44.5%) procedures in 2017, reflecting the widespread implementation of ABO-incompatible kidney transplantation. The top five hospitals conducted 59.6% of the procedures, which showed a centralized distribution. CONCLUSIONS: The most common indication was renal diseases. The number of TPE procedures performed annually increased by approximately 3.7 times from 2008 to 2017. This study shows that other than a registry, claims data can be successfully used to analyze various aspects of TPE procedures on a nationwide scale. This approach could be used by other countries, especially those that have national health insurance.

Aerodigestive Clinics as Emerging Pediatric Care Model: The First 100 Patients in Israel.

BACKGROUND: Aerodigestive clinics are run by interdisciplinary medical and surgical teams, and provide complex care coordination and combined endoscopies. OBJECTIVES: To describe the design and patient population of the first pediatric aerodigestive center in Israel. METHODS: A retrospective single-center cohort study was conducted describing patients followed in the aerodigestive clinic of Schneider Children's Medical Center of Israel, a tertiary pediatric hospital, between its inception in January 2017 and June 2020. RESULTS: During the study period, 100 patients were seen at the combined respiratory and digestive (NoAM) clinic, with a total of 271 visits. Median age at first assessment was 29.5 months (range 3-216). Fifty-six patients (56%) had esophageal atresia and tracheoesophageal fistula. Thirty-nine patients had an identified genetic disorder, 28 had a primary airway abnormality, 28 were oxygen dependent, and 21 were born premature. Fifty-two patients underwent triple endoscopy, consisting of flexible bronchoscopy, rigid bronchoscopy, and gastroscopy. In 33 patients, esophageal dilatation was necessary. Six patients underwent posterior tracheopexy at a median of 6 months of age (range 5 days to 8 years) all with ensuing symptom improvement. The total mean parental satisfaction score on a Likert-type scale of 1-5 (5 = highest satisfaction) was 4.5. CONCLUSIONS: A coordinated approach is required to provide effective care to the growing population of children with aerodigestive disorders. The cross fertilization between multiple disciplines offers a unique opportunity to develop high quality and innovative care. Outcome measures must be defined to objectively measure clinical benefit.

Generation of Hepatobiliary Cell Lineages from Human Induced Pluripotent Stem Cells: Applications in Disease Modeling and Drug Screening.

The possibility to reproduce key tissue functions in vitro from induced pluripotent stem cells (iPSCs) is offering an incredible opportunity to gain better insight into biological mechanisms underlying development and disease, and a tool for the rapid screening of drug candidates. This review attempts to summarize recent strategies for specification of iPSCs towards hepatobiliary lineages -hepatocytes and cholangiocytes-and their use as platforms for disease modeling and drug testing. The application of different tissue-engineering methods to promote accurate and reliable readouts is discussed. Space is given to open questions, including to what extent these novel systems can be informative. Potential pathways for improvement are finally suggested.

COVID-19 and the digestive system: implications for transforming care delivery.

The pandemic caused by SARS-CoV-2 has posed an unprecedented challenge to health systems, leading in many countries to the collapse of health care and a lack of preventive measures both for the most vulnerable sections of the population and among healthcare professionals.

Challenges in the management of life-threatening complications caused by a rare case of sarcoid-lymphoma syndrome.

PURPOSE: The sarcoid-lymphoma syndrome is a rare condition where both entities co-exist in the same patient. Overlapping clinical manifestations, imaging findings, and pathological characteristics pose both a diagnostic as well as therapeutic challenge, especially in the setting of life-threatening complications. The objective of this case report is to highlight rare complications caused by abdominal sarcoidosis as well as a subsequently diagnosed non-Hodgkin lymphoma. METHODS: A 35-year-old man presented with massive upper gastrointestinal bleeding caused by a large retroperitoneal mass. Following several endoscopic and radiologic interventions, successful hemostasis could only be achieved by an emergency Whipple procedure. Biopsies of the mass showed an abdominal manifestation of sarcoidosis and corticosteroid therapy was started. The patient required several additional emergency surgeries due to a complicated bronchoperitoneal fistula, splenic abscess, perforation of the sigmoid colon, small bowel leakage, and repetitive intra-abdominal bleeding. RESULTS: Histopathological findings finally revealed a concurrent lymphoma, as clinically suspected earlier. Ultimately, polychemotherapy was administered. CONCLUSION: A concurrent lymphoma can lead to emergency surgery and should be considered when sarcoidosis treatment does not improve symptoms, lymphadenopathy occurs, or hematologic changes persist under therapy.

COVID-19 and the digestive system: protection and management during the SARS-CoV-2 pandemic.

The purpose of this rapid review is to provide an update on the impact of SARS-CoV-2 infection on Gastroenterology and Hepatology departments, our patients, and our new way of working. The gastrointestinal tract and the liver are affected by SARS-CoV-2, especially in patients with immunosuppressive therapies. Patients with liver transplantation should be followed closely. Digestive endoscopy is a high-risk procedure for the transmission of SARS-CoV-2. While the pandemic lasts, we must adapt its indications and promote protective measures for patients and healthcare professionals alike. The COVID-19 pandemic has changed our priorities and the way we work, although we do not know what the repercussions will be after normality is reinstated.

Resumption of activity in gastroenterology departments. Recommendations by SEPD, AEEH, GETECCU and AEG. / Restablecimiento de la actividad en los servicios de Digestivo. Recomendaciones de la SEPD, AEEH, GETECCU y AEG.

The set of measures proposed by SEPD, AEEH, GETECCU and AEG are aimed to help departments in their resumption of usual activity. We have prepared a number of practical recommendations regarding patient management and the stepwise resumption of healthcare activity. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them; in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. The general objectives of these recommendations include: (a)To protect our patients against the risks of infection with SARS-CoV-2 and to provide them with high-quality care. (b)To protect all healthcare professionals against the risks of infection with SARS-CoV-2. (c)To resume normal functioning of our departments in a setting of ongoing risk for infection with SARS-CoV-2.

Best Practice Update: Incorporating Psychogastroenterology Into Management of Digestive Disorders.

Chronic digestive diseases, including irritable bowel syndrome, gastroesophageal reflux disease, and inflammatory bowel diseases, cannot be disentangled from their psychological context-the substantial burden of these diseases is co-determined by symptom and disease severity and the ability of patients to cope with their symptoms without significant interruption to daily life. The growing field of psychogastroenterology focuses on the application of scientifically based psychological principles and techniques to the alleviation of digestive symptoms. In this Clinical Practice Update, we describe the structure and efficacy of 2 major classes of psychotherapy-cognitive behavior therapy and gut-directed hypnotherapy. We focus on the impact of these brain-gut psychotherapies on gastrointestinal symptoms, as well as their ability to facilitate improved coping, resilience, and self-regulation. The importance of the gastroenterologist in the promotion of integrated psychological care cannot be overstated, and recommendations are provided on how to address psychological issues and make an effective referral for brain-gut psychotherapy in routine practice.

Stem and Progenitor Cells in the Pathogenesis and Treatment of Digestive Diseases.

The global epidemic of chronic degenerative diseases expands rapidly. The pathogenesis of these noncommunicable disorders revolves around innate immunity, microbiome, and stem cell alterations. Understanding the mechanisms behind stem cell biology and their regulatory pathways is a key to understanding the origin of human disease. Stem cells are involved in tissue and organ damage and regeneration. The evidence is mounting that not only eukaryotic cells but also gut microbiota may release extracellular microvesicles that are absorbed from the gut into the portal and systemic circulation. Linking the fields of stem cells, innate immunity and microbiome research opens up new avenues to develop novel diagnostic (e.g., biomarkers), therapeutic (e.g., microbiome modulation, stem cell-based medicines), and prognostic (personalized diets) tools. In this chapter, we present the short overview of various stem and progenitor cells of adult tissues circulating in peripheral blood and their role in the pathogenesis and treatment of digestive diseases. We also briefly discuss the role of host-stem cell-microbial interactions as a new frontier of research in gastroenterology.

An international, multicenter, comparative trial of EUS-guided gastrogastrostomy-assisted ERCP versus enteroscopy-assisted ERCP in patients with Roux-en-Y gastric bypass anatomy.

BACKGROUND AND AIMS: ERCP is challenging in patients with Roux-en-Y gastric bypass (RYGB) anatomy. EUS-guided gastrogastrostomy (GG) creation is a promising novel technique to access the excluded stomach to facilitate conventional ERCP. We aimed to compare procedural outcomes and adverse events (AEs) between EUS-guided GG-assisted ERCP (EUS-GG-ERCP) and enteroscopy-assisted ERCP (e-ERCP) in patients with RYGB. METHODS: Patients with RYGB anatomy who underwent EUS-GG-ERCP or e-ERCP between 2014 and 2016 at 5 tertiary centers were included. The primary outcome was technical success of ERCP, defined as successful cannulation of the selected duct with successful intervention as intended. Secondary outcomes included total procedural time (in the EUS-GG group, total procedural time included EUS-GG creation plus ERCP procedure time), length of hospital stay, and rate/severity of AEs graded according to the American Society for Gastrointestinal Endoscopy lexicon. RESULTS: A total of 60 patients (mean age, 57.2 ± 13.2; 75% women) were included, of whom 30 (50%) underwent EUS-GG-ERCP and 30 (50%) underwent e-ERCP (double-balloon enteroscope ERCP, 19; single-balloon enteroscope ERCP, 11). The technical success rate was significantly higher in the EUS-GG-ERCP versus the e-ERCP group (100% vs 60.0%, P < .001). Total procedure time was significantly shorter in patients who underwent EUS-GG-ERCP (49.8 minutes vs 90.7 minutes, P < .001). Postprocedure median length of hospitalization was shorter in the EUS-GG group (1 vs 10.5 days, P = .02). Rate of AEs was similar in both groups (10% vs 6.7%, P = 1). CONCLUSIONS: EUS-GG-ERCP may be superior to e-ERCP in patients with RYGB anatomy in terms of a higher technical success and shorter procedural times and offers a similar safety profile.

Consensus and contentious statements on the use of probiotics in clinical practice: A south east Asian gastro-neuro motility association working team report.

The concept of consuming microorganisms in the treatment of a medical condition and in health maintenance has gained much attraction, giving rise to an abundance of medical claims and of health supplements. This study identified relevant clinical questions on the therapeutic use of probiotics and reviewed the literature in irritable bowel syndrome, inflammatory bowel disease, impaired intestinal immunity, liver disease, intestinal infections, and common childhood digestive disorders. Statements were developed to address these clinical questions. A panel of experienced clinicians was tasked to critically evaluate and debate the available data. Both consensus and contentious statements are presented to provide to clinicians a perspective on the potential of probiotics and importantly their limitations.