Safety of artificial intelligence-assisted optical diagnosis for leaving colorectal polyps in situ during colonoscopy (PRACTICE): a non-inferiority, randomised controlled trial.

Background: Guidelines recommend leaving in situ rectosigmoid polyps diagnosed during colonoscopy that are 5 mm or smaller if the endoscopist optically predicts them to be non-neoplastic. However, no randomised controlled trial has been done to examine the efficacy and safety of this strategy.

Methods: This open-label, multicentre, non-inferiority, randomised controlled trial enrolled adults age 18 years or older undergoing colonoscopy for screening, surveillance, or clinical indications across four Italian centres.

Case Report: Hemolytic anemia secondary to infliximab treatment in a patient with ulcerative colitis.

Infliximab, a monoclonal antibody targeting tumor necrosis factor-alpha (TNF-α), is widely used in treating inflammatory bowel diseases (IBD), including ulcerative colitis (UC). While generally well-tolerated, infliximab is associated with rare but significant adverse effects, including autoimmune hemolytic anemia (AIHA). This report describes the case of a 54-year-old male diagnosed with UC, who developed hemolytic anemia secondary to infliximab therapy after 1 year of treatment.

Texture and color enhancement imaging versus high definition white-light endoscopy for detection of colorectal neoplasia: a randomized trial.

Background:  Texture and color enhancement imaging (TXI) was recently proposed as a substitute for standard high definition white-light imaging (WLI) to increase lesion detection during colonoscopy. This international, multicenter randomized trial assessed the efficacy of TXI in detection of colorectal neoplasia.

Methods:  Consecutive patients aged ≥ 40 years undergoing screening, surveillance, or diagnostic colonoscopies at five centers (Italy, Germany, Japan) between September 2021 and May 2022 were enrolled.

GATA6 Deficiency Leads to Epithelial Barrier Dysfunction and Enhances Susceptibility to Gut Inflammation.

Background And Aims: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases [IBD], but the mechanisms that lead to such a defect are not fully understood. This study was aimed at characterising the factors involved in the defective barrier function in IBD.

Methods: Transcriptome analysis was performed on colon samples taken from healthy controls [CTR] and IBD patients.

Targeting IL-23 in Crohn's disease.

Interleukin (IL)-23, a cytokine produced by antigen presenting cells, targets both T cells and non-T cell types with the downstream effect of enhancing inflammatory pathways. Genome-wide association studies and data from human and mouse models of intestinal inflammation support the pathogenic role of IL-23 in Crohn's disease (CD), an immune-mediated disorder that can involve any part of the gastrointestinal tract. Areas covered: This review summarizes the available data on the role of IL-23 in CD and discusses the therapeutic relevance of blocking the function of IL-23 in this disorder.

Reciprocal Regulation Between Smad7 and Sirt1 in the Gut.

In inflammatory bowel disease (IBD) mucosa, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine transforming growth factor-β1, due to post-transcriptional mechanisms that enhance Smad7 acetylation status thus preventing ubiquitination-mediated proteosomal degradation of the protein. IBD-related inflammation is also marked by defective expression of Sirt1, a class III NAD+-dependent deacetylase, which promotes ubiquitination-mediated proteosomal degradation of various intracellular proteins and triggers anti-inflammatory signals. The aim of our study was to determine whether, in IBD, there is a reciprocal regulation between Smad7 and Sirt1.

Follistatin-like protein 1 sustains colon cancer cell growth and survival.

Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein, which controls several physiological and pathological events. FSTL1 expression is deregulated in many tumors, but its contribution to colon carcinogenesis is not fully understood. Here, we investigated the expression and functional role of FSTL1 in colorectal cancer (CRC).

Advances in understanding the role of cytokines in inflammatory bowel disease.

Cytokines represent the key pathophysiologic elements that govern the initiation, progression, and, in some circumstances, the resolution of the inflammation occurring in inflammatory bowel disease (IBD). Areas covered: In this review, we will focus on the main effector and anti-inflammatory cytokines produced in IBD and discuss the results of recent trials in which cytokine-based therapy has been used for treating IBD patients. Expert commentary: The possibility to sample mucosal biopsies from IBD patients and analyze which molecular pathways are prominent during the active phases of the disease and the easy access to various models of experimental colitis has largely advanced our understanding about the role of cytokines in IBD.

Oligonucleotide-Based Therapies for Inflammatory Bowel Disease.

The growing understanding of the immunopathogenesis of inflammatory bowel diseases (IBDs) has contributed to the identification of new targets whose expression/activity can be modulated for therapeutic purposes. Several approaches have been employed to develop selective pharmaceutical compounds; among these, antisense oligonucleotides (ASOs) or synthetic oligonucleotides represent a valid option for inhibiting or enhancing, respectively, the expression/function of molecules that have been implicated in the control of IBD-related inflammation. In this context, data have been accumulated for the following compounds: alicaforsen, an ASO targeting intercellular adhesion molecule-1, a transmembrane glycoprotein that regulates rolling and adhesion of leukocytes to inflamed intestine; DIMS0150 and BL-7040, two oligonucleotides that enhance Toll-like receptor-9 activity; Mongersen, an ASO that inhibits Smad7, thereby restoring transforming growth factor-β1/Smad-associated signaling; STNM01, a double-stranded RNA oligonucleotide silencing carbohydrate sulfotransferase, an enzyme involved in fibrogenic processes, and hgd40, a specific DNAzyme inhibiting expression of the transcription factor GATA3.

Knockdown of Smad7 With a Specific Antisense Oligonucleotide Attenuates Colitis and Colitis-Driven Colonic Fibrosis in Mice.

Background: In Crohn's disease (CD), the pathogenic immune response is associated with high Smad7, an inhibitor of TGF-β1 signaling. Smad7 knockdown with Mongersen, a specific antisense oligonucleotide-containing compound, restores TGF-β1 activity leading to inhibition of inflammatory signals and associates with clinical benefit in CD patients. As TGF-β1 is pro-fibrogenic, it remains unclear whether Mongersen-induced Smad7 inhibition increases the risk of intestinal fibrosis.

Interleukin-34 sustains pro-tumorigenic signals in colon cancer tissue.

Interleukin-34 (IL-34), a cytokine produced by a wide range of cells, binds to the macrophage colony-stimulating factor receptor (M-CSFR-1) and receptor-type protein-tyrosine phosphatase zeta (PTP-z) and controls myeloid cell differentiation, proliferation and survival. various types of cancers over-express IL-34 but the role of the cytokine in colorectal cancer (CRC) remains unknown. We here investigated the expression and functional role of IL-34 in CRC.

Smad7 knockdown activates protein kinase RNA-associated eIF2α pathway leading to colon cancer cell death.

Upregulation of Smad7, an inhibitor of transforming growth factor-β1 (TGF-β1), occurs in sporadic colorectal cancer (CRC) and knockdown of Smad7 inhibits CRC cell growth, a phenomenon that associates with decreased expression of cell division cycle 25 homolog A and arrest of cells in the S phase of the cell cycle. These findings occur in CRC cells unresponsive to TGF-β1, thus suggesting the existence of a Smad7-mediated TGF-β1-independent mechanism that controls CRC cell behavior. Here we show that Smad7 inhibition with a specific Smad7 antisense oligonucleotide upregulates eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, a transcription factor involved in the regulation of cell cycle arrest and induction of cell death, and induces activating transcription factor 4 (ATF4) and CCAAT/enhancer binding protein homology protein (CHOP), two downstream targets of eIF2α.

High Smad7 sustains inflammatory cytokine response in refractory coeliac disease.

Refractory coeliac disease (RCD) is a form of coeliac disease (CD) resistant to gluten-free diet and associated with elevated risk of complications. Many effector cytokines over-produced in the gut of patients with RCD are supposed to amplify the tissue-destructive immune response, but it remains unclear if the RCD-associated mucosal inflammation is sustained by defects in counter-regulatory mechanisms. The aim of the present study was to determine whether RCD-related inflammation is marked by high Smad7, an intracellular inhibitor of transforming growth factor-β (TGF-β ) activity.

Mongersen, an oral Smad7 antisense oligonucleotide, in patients with active Crohn's disease.

In Crohn's disease (CD), the tissue-damaging inflammation is sustained by defects of counter-regulatory mechanisms, which normally inhibit immune-inflammatory signals and promote repair of mucosal injury. In particular, in inflamed gut of CD patients there are elevated levels of Smad7, an intracellular protein that inhibits the function of transforming growth factor (TGF)-β1. Knockdown of Smad7 with a specific antisense oligonucleotide, named mongersen, restores TGF-β1 activity thus leading to suppression of inflammatory pathways and resolution of colitis in mice.

Tofacitinib for the treatment of ulcerative colitis.

Introduction: Management of patients with active ulcerative colitis (UC), one of the most frequent inflammatory bowel diseases in human beings, is mainly based on the use of mesalamine and corticosteroids. Since in the long-term, these two drugs may be ineffective in nearly one third of the patients, immunosuppressants and/or biologics are needed to control disease activity.

Areas Covered: The marked activation of JAK/STAT molecules in inflamed mucosa of UC patients and the demonstration that UC-associated mucosal injury is driven by soluble factors that signal through JAK/STAT pathways led to investigation of JAK inhibitors for the treatment of active UC.

Impact of endoscopic ultrasound-guided fine-needle aspiration and multidisciplinary approach in the management of abdominal or mediastinal mass.

Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a useful tool for the diagnosis of suspected abdominal or mediastinal neoplastic lesions.

Aim: To evaluate the impact of EUS-FNA and multidisciplinary approach on the diagnostic work-up and therapeutic management of patients with abdominal or mediastinal neoplastic lesions.

Patients And Methods: One hundred and twenty patients (69 men, median age 65 years) with a suspected abdominal or mediastinal neoplastic mass at computed tomography or MRI underwent EUS-FNA.

A sonographic lesion index for Crohn's disease helps monitor changes in transmural bowel damage during therapy.

Background & Aims: Therapeutic antibodies against tumor necrosis factor α (anti-TNF) are effective in patients with Crohn's disease (CD). Mucosal healing is a surrogate marker of efficacy, but little is known about the effects of anti-TNF agents on structural damage in the intestine. Small-intestine contrast ultrasonography (SICUS) is a valuable tool for assessing CD lesions.