Liver cancer development driven by the AP-1/c-Jun~Fra-2 dimer through c-Myc.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. HCC incidence is on the rise, while treatment options remain limited. Thus, a better understanding of the molecular pathways involved in HCC development has become a priority to guide future therapies.

Modified-Release Phosphatidylcholine (LT-02) for Ulcerative Colitis: Two Double-Blind, Randomized, Placebo-Controlled Trials.

Background & Aims: The aim of this study was to evaluate the efficacy of LT-02, a novel modified-release phosphatidylcholine (PC) formulation, for induction and maintenance of remission in patients with mild to moderate ulcerative colitis (UC) and inadequate response to mesalamine.

Methods: LT-02 was evaluated in a multicenter double-blind, randomized, placebo-controlled study comprising a 12-week induction trial (PCG-2), followed by a 48-week maintenance trial (PCG-4). In PCG-2, patients were randomized 1:1:1 to treatment with 0.

Prevalence of delirium in gastroenterology/hepatology units: A cross-sectional study.

Prevalence rates of delirium amount to 22.0% within acute-care settings. In contrast, 30-40% of patients with liver cirrhosis may develop hepatic encephalopathy, a condition that has been classified as a syndrome of delirium, based on recent pathophysiology findings.

[Diversity in gastroenterology - A focus on inflammatory bowel diseases].

Factors related to patient diversity may play a major role in the pathogenesis and clinical manifestation of intestinal and liver diseases and should be considered during diagnostic workup and therapeutic decisions. Here we discuss how diversity factors such as gender, ethnicity, age and socioeconomic parameters may affect the manifestation and disease course of inflammatory bowel diseases (IBD, i.e.

Questions to consider when caring for patients with ulcerative colitis.

Although the management of patients with ulcerative colitis (UC) is well defined by national and international guidelines, there are many debates and open questions related to daily care of UC patients. Here, we aimed to review topics with high clinical relevance including therapy algorithms, potential biomarkers for disease prognosis and response to therapy, the role of interventions targeting the gut microbiota, insights from head-to-head trials, novel UC medications, exit strategies, the impact of COVID19 on UC, care of patients with acute severe disease, cancer screening, and the role of surgery.

Exhaustion of CD39-Expressing CD8 T Cells in Crohn's Disease Is Linked to Clinical Outcome.

Background & Aims: Exhaustion of CD8 T cells has been suggested to inform different clinical outcomes in Crohn's disease, but detailed analyses are lacking. This study aimed to identify the role of exhaustion on a single-cell level and identify relevant CD8 T cell populations in Crohn's disease.

Methods: Blood and intestinal tissue from 58 patients with Crohn's disease (active disease or remission) were assessed for CD8 T cell expression of exhaustion markers and their cytokine profile by highly multiplexed flow and mass cytometry.

Reduction of esophageal stent migration rate with a novel over-the-scope fixation device (with video).

Background And Aims: Self-expandable metal stent (SEMS) placement is routinely performed in a variety of benign and malignant GI diseases. One of the most frequent adverse events after esophageal SEMS placement is stent migration. We evaluated a novel over-the-scope clip device (stentfix OTSC; Ovesco Endoscopy, Tuebingen, Germany) designed and approved for SEMS fixation.

[Effects of SARS-CoV-2 Infection on Symptoms and Therapy of Inflammatory Bowel Disease].

Introduction: The influence of a SARS-CoV-2 infection on inflammatory bowel disease (IBD) has not yet been well characterized and it is unclear whether this requires an adaptation of the immunosuppressive therapy.

Methods: A national register was established for the retrospective documentation of clinical parameters and changes in immunosuppressive therapy in SARS-CoV-2 infected IBD patients.

Results: In total, only 3 of 185 IBD patients (1.

MiR-100 overexpression attenuates high fat diet induced weight gain, liver steatosis, hypertriglyceridemia and development of metabolic syndrome in mice.

Background: Diet-induced obesity can result in the development of a diverse spectrum of cardiovascular and metabolic diseases, including type 2 diabetes, dyslipidemia, non-alcoholic liver steatosis and atherosclerotic disease. MicroRNAs have been described to be important regulators of metabolism and disease development.

Methods: In the current study, we investigated the effects of ubiquitous miR-100 overexpression on weight gain and the metabolic phenotype in a newly generated transgenic mouse strain under normal chow and high fat diet and used microarray expression analysis to identify new potential target genes of miR-100.

Diagnostic and therapeutic challenge of unclassifiable enteropathies with increased intraepithelial CD103 CD8 T lymphocytes: a single center case series.

Objectives: Chronic diarrhea, villous atrophy and/or increased intraepithelial T-lymphocytes (IEL) occur in many inflammatory disorders including celiac disease (CD). However, a definite diagnosis is difficult to make in some patients despite an extensive diagnostic work-up. Clinical outcomes and histological phenotypes of such patients we refer to as unclassifiable enteropathy (UEP) remain unclear.

Diethylnitrosamine-induced liver tumorigenesis in mice.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third leading cause of cancer related mortality with a 10 year survival rate of merely 22-35%. Tumorigenesis frequently occurs in patients with chronic liver disease where continued liver cell damage, compensatory proliferation and inflammation provide the basis for tumor initiation, promotion and progression. Animal models of HCC are particularly useful to better understand molecular events underlying liver tumorigenesis.

[Acute and chronic diarrhea: a roadmap to differential diagnosis and therapy].

Diarrhea is among the most frequently reported symptoms in clinical practice. Acute diarrhea is usually caused by infectious agents with a self-limited disease course. In contrast, differential diagnosis of chronic diarrhea may be challenging.

Ustekinumab Inhibits T Follicular Helper Cell Differentiation in Patients With Crohn's Disease.

Background & Aims: The pathogenesis of chronic inflammatory bowel diseases (Crohn's disease [CD] and ulcerative colitis) involves dysregulated TH1 and TH17 cell responses, which can be targeted therapeutically by the monoclonal antibody Ustekinumab directed against the joint p40 subunit of IL-12 and IL-23. These cytokines may also regulate the differentiation of T follicular helper (TFH) cells, which promote B cell function in germinal centers. However, the role of TFH cells in CD pathogenesis and impact of Ustekinumab therapy on TFH cell fate in patients are poorly defined.

Tofacitinib in Treatment-Refractory Moderate to Severe Ulcerative Colitis: Real-World Experience from a Retrospective Multicenter Observational Study.

(1) Background: Tofacitinib is approved in Europe for the treatment of adults with moderately to severely active ulcerative colitis since 2018. Real-world efficacy and safety data are currently scarce. (2) Methods: We performed a retrospective multicenter study at three German tertiary outpatient clinics for inflammatory bowel diseases and included all patients who started tofacitinib therapy between August 2018 and March 2020.

Ustekinumab serum concentrations are associated with clinical outcomes in Crohn's disease - a regional multi-center pilot study.

Background And Aim:  The role of therapeutic drug monitoring (TDM) in ustekinumab (UST) therapy for Crohn's disease (CD) has not been established, as only few studies have analyzed the relationship between UST serum concentrations and clinical outcome. In this pilot study, we retrospectively examined the potential of UST-concentrations (cUST) 8 weeks after induction (cUSTw8) to predict clinical response at week 16.

Methods:  Serum samples and clinical data from patients (n = 72) with moderate to severely active CD who received intravenous induction with UST were retrospectively analyzed.

Extracellular ATP and Purinergic P2Y Receptor Signaling Promote Liver Tumorigenesis in Mice by Exacerbating DNA Damage.

Release of ATP to the extracellular compartment and subsequent activation of purinergic receptors is a conserved mechanism mediating inflammatory responses and cell fate decisions in various organs including the liver. Previous findings suggest that extracellular ATP may promote liver tumorigenesis, however, the underlying mechanisms are poorly understood. Therefore, our aim was to dissect the functions of extracellular ATP and P2Y receptors (P2YR) during hepatocarcinogenesis.

Esophageal lichen planus: towards diagnosis of an underdiagnosed disease.

Although lichen planus (LP) is a common skin disorder, the prevalence of esophageal involvement (ELP) and its clinical manifestations are poorly defined. We aimed to establish diagnostic criteria and characterize disease outcomes of ELP. Clinical, endoscopic, histological, and immunofluorescence data from consecutive patients with known LP between 2013 and 2018 were analyzed.

Seasonal variability of vitamin D status in patients with inflammatory bowel disease - A retrospective cohort study.

Objectives: Vitamin D deficiency predicts unfavorable disease outcomes in inflammatory bowel disease. Endogenous vitamin D synthesis is affected by seasonal factors including sunlight exposure, raising the question whether seasonality determines the risk of vitamin D deficiency and may mask other clinical risk factors.

Methods: Univariable and multiple regression analyses were performed in a retrospective cohort of 384 patients to determine risk factors for vitamin D deficiency.

Vitamin D Inhibits Pro-Inflammatory T Cell Function in Patients With Inflammatory Bowel Disease.

Background And Aims: Dysregulated T cell responses contribute to the pathogenesis of inflammatory bowel disease [IBD]. Because vitamin D [vitD] deficiency is a risk factor for adverse disease outcomes, we aimed to characterize the impact of vitD on intestinal and peripheral T cell profiles.

Methods: T cells were isolated from peripheral blood and intestinal biopsies of IBD patients, incubated with vitD and characterized by flow cytometry.

Gastric cancer and paraneoplastic dermatomyositis as complications of an unrecognized juvenile polyposis syndrome.

Juvenile polyposis syndrome is a rare autosomal-dominant disorder characterized by multiple hamartomatous polyps in the gastrointestinal tract. It is associated with an increased risk of gastrointestinal cancer. We report the case of a 49-year-old woman presenting with proximal muscle weakness, weight loss, severe anemia, and melena.

The transcription factor c-Jun/AP-1 promotes liver fibrosis during non-alcoholic steatohepatitis by regulating Osteopontin expression.

Progression of non-alcoholic fatty liver disease (NAFLD) from steatosis to non-alcoholic steatohepatitis (NASH) is a key step of NASH pathogenesis. The AP-1 transcription factor c-Jun is an important regulator of hepatic stress responses, but its contribution to NASH pathogenesis remains poorly defined. We therefore addressed c-Jun expression in liver biopsies of patients with steatosis and NASH.