Development of a deep learning algorithm for Paneth cell density quantification for inflammatory bowel disease.

Background: Alterations in ileal Paneth cell (PC) density have been described in gut inflammatory diseases such as Crohn's disease (CD) and could be used as a biomarker for disease prognosis. However, quantifying PCs is time-intensive, a barrier for clinical workflow. Deep learning (DL) has transformed the development of robust and accurate tools for complex image evaluation.

TL1A: A model for a precision medicine approach in the treatment of Crohn's disease and ulcerative colitis.

Inflammatory bowel disease (IBD) is a collective term for chronic inflammatory diseases of the intestinal tract. The term IBD encompasses two main forms, Crohn's disease (CD) and Ulcerative colitis (UC). CD is characterized by inflammation throughout the length of the gut, especially the ileum and colon, and is often complicated with fistulae and/or intestinal strictures.

Toll-like receptor 7 protects against intestinal inflammation and restricts the development of colonic tissue-resident memory CD8 T cells.

Introduction: The maintenance of intestinal homeostasis depends on a complex interaction between the immune system, intestinal epithelial barrier, and microbiota. Alteration in one of these components could lead to the development of inflammatory bowel diseases (IBD). Variants within the autophagy gene have been implicated in susceptibility and severity of Crohn's disease (CD).

Imaging in Inflammatory Bowel Disease.

The incidence of inflammatory bowel disease (IBD) is rising globally. We need more tools and techniques in our armamentarium for early diagnosis, tight monitoring, and to assess disease complications of IBD. This article reviews the role of cross-sectional imaging, mainly computed tomography, MRI, and intestinal ultrasound (IUS) in IBD and its advantages, disadvantages, and limitations.

Phase 2 Trial of Anti-TL1A Monoclonal Antibody Tulisokibart for Ulcerative Colitis.

Background: Tulisokibart is a tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody in development for the treatment of moderately to severely active ulcerative colitis. A genetic-based diagnostic test was designed to identify patients with an increased likelihood of response.

Methods: We randomly assigned patients with glucocorticoid dependence or failure of conventional or advanced therapies for ulcerative colitis to receive intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10) or placebo.

Immunohistochemistry annotations enhance AI identification of lymphocytes and neutrophils in digitized H&E slides from inflammatory bowel disease.

Background And Objective: Histologic assessment of the immune infiltrate in H&E slides is vital in diagnosing and managing inflammatory bowel diseases, but these assessments are subjective and time-consuming even for those with expertise. The development of deep learning models to aid in these assessments has been limited by the paucity of image data with reliably annotated immune cells available for training.

Methods: To address these challenges, we developed a pipeline that automates the neutrophil and lymphocyte labeling in ROIs from digital H&E slides.

Artificial Intelligence- and Physician-Interpreted Stool Image Characteristics Correlate With C-Reactive Protein Among Inpatients With Acute Severe Ulcerative Colitis: A Pilot Study.

Background: Stool characteristics are used as a measure of ulcerative colitis (UC) disease activity, but they have not been validated against objective inflammation. We aimed to determine whether stool characteristics measured by trained artificial intelligence (AI) and physicians correlate with inflammation in UC.

Methods: Patients hospitalized with acute severe UC (ASUC) were asked to capture images of all bowel movements using a smartphone application (Dieta®).

Age-related patterns of microbial dysbiosis in multiplex inflammatory bowel disease families.

Objective: IBD is characterised by dysbiosis, but it remains unclear to what extent dysbiosis develops in unaffected at-risk individuals. To address this, we investigated age-related patterns of faecal and serum markers of dysbiosis in high-risk multiplex IBD families (two or more affected first-degree relatives).

Design: Faecal and serum samples were collected from multiplex IBD and control families (95 IBD, 292 unaffected, 51 controls).

Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials.

Importance: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown.

Objective: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis.

Design, Setting, And Participants: Two phase 3 randomized clinical trials were conducted.

Radiomics-Based Analysis of Intestinal Ultrasound Images for Inflammatory Bowel Disease: A Feasibility Study.

Background: The increasing adoption of intestinal ultrasound () for monitoring inflammatory bowel diseases () by IBD providers has uncovered new challenges regarding standardized image interpretation and limitations as a research tool. Artificial intelligence approaches can help address these challenges. We aim to determine the feasibility of radiomic analysis of IUS images and to determine if a radiomics-based classification model can accurately differentiate between normal and abnormal IUS images.

Gut microbiome and cardiometabolic comorbidities in people living with HIV.

Background: Despite modern antiretroviral therapy (ART), people living with HIV (PLWH) have increased relative risk of inflammatory-driven comorbidities, including cardiovascular disease (CVD). The gut microbiome could be one of several driving factors, along with traditional risk factors and HIV-related risk factors such as coinfections, ART toxicity, and past immunodeficiency.

Results: PLWH have an altered gut microbiome, even after adjustment for known confounding factors including sexual preference.

Profiling phagosome proteins identifies PD-L1 as a fungal-binding receptor.

Phagocytosis is the process by which myeloid phagocytes bind to and internalize potentially dangerous microorganisms. During phagocytosis, innate immune receptors and associated signalling proteins are localized to the maturing phagosome compartment, forming an immune information processing hub brimming with microorganism-sensing features. Here we developed proximity labelling of phagosomal contents (PhagoPL) to identify proteins localizing to phagosomes containing model yeast and bacteria.

Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease.

Background & Aims: Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD.

Methods: Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort).

AI-luminating Artificial Intelligence in Inflammatory Bowel Diseases: A Narrative Review on the Role of AI in Endoscopy, Histology, and Imaging for IBD.

Endoscopy, histology, and cross-sectional imaging serve as fundamental pillars in the detection, monitoring, and prognostication of inflammatory bowel disease (IBD). However, interpretation of these studies often relies on subjective human judgment, which can lead to delays, intra- and interobserver variability, and potential diagnostic discrepancies. With the rising incidence of IBD globally coupled with the exponential digitization of these data, there is a growing demand for innovative approaches to streamline diagnosis and elevate clinical decision-making.

A randomized controlled trial of a proactive analgesic protocol demonstrates reduced opioid use among hospitalized adults with inflammatory bowel disease.

Most hospitalized patients with inflammatory bowel disease (IBD) experience pain. Despite the known risks associated with opioids in IBD including risk for misuse, overdose, infection, readmission, and even death, opioid use is more prevalent in IBD than any other chronic gastrointestinal condition. Most hospitalized IBD patients receive opioids; however, opioids have not been shown to improve pain during hospitalization.

Comparative Persistence of Non-tumor Necrosis Factor (TNF) vs. TNF Antagonists for Post-operative Prophylaxis in Crohn's Disease (CD).

Background: The comparative safety and effectiveness of available biologics for post-operative prophylaxis in Crohn's disease (CD) is uncertain. Drug persistence may serve as a real-world proxy for tolerability and effectiveness. We evaluated the comparative persistence of non-TNF and TNF antagonists for post-operative prophylaxis and their comparative effectiveness for preventing early endoscopic post-operative recurrence (POR).

Clinical Utility of SARS-CoV-2 Serological Testing and Defining a Correlate of Protection.

Herein, we review established clinical use cases for SARS-CoV-2 antibody measures, which include diagnosis of recent prior infection, isolating high titer convalescent plasma, diagnosing multisystem inflammatory syndrome in children (MIS-C), and booster dosing in the immunosuppressed and other populations. We then address whether an antibody correlate of protection (CoP) for SARS-CoV-2 has been successfully defined with the following considerations: Antibody responses in the immunocompetent, vaccine type, variants, use of binding antibody tests vs. neutralization tests, and endpoint measures.

α-Ketoglutarate-Dependent KDM6 Histone Demethylases and Interferon-Stimulated Gene Expression in Lupus.

Objective: We aimed to investigate the hypothesis that interferon (IFN)-stimulated gene (ISG) expression in systemic lupus erythematosus (SLE) monocytes is linked to changes in metabolic reprogramming and epigenetic regulation of ISG expression.

Methods: Monocytes from healthy volunteers and patients with SLE at baseline or following IFNα treatment were analyzed by extracellular flux analysis, proteomics, metabolomics, chromatin immunoprecipitation, and gene expression. The histone demethylases KDM6A/B were inhibited using glycogen synthase kinase J4 (GSK-J4).

Hexokinase dissociation from mitochondria promotes oligomerization of VDAC that facilitates NLRP3 inflammasome assembly and activation.

NLRP3 inflammasome activation is a highly regulated process for controlling secretion of the potent inflammatory cytokines IL-1β and IL-18 that are essential during bacterial infection, sterile inflammation, and disease, including colitis, diabetes, Alzheimer's disease, and atherosclerosis. Diverse stimuli activate the NLRP3 inflammasome, and unifying upstream signals has been challenging to identify. Here, we report that a common upstream step in NLRP3 inflammasome activation is the dissociation of the glycolytic enzyme hexokinase 2 from the voltage-dependent anion channel (VDAC) in the outer membrane of mitochondria.

Sex-Dimorphic Analyses Identify Novel and Sex-Specific Genetic Associations in Inflammatory Bowel Disease.

Background: Sex is an integral variable often overlooked in complex disease genetics. Differences between sexes have been reported in natural history, disease complications, and age of onset in inflammatory bowel disease (IBD). While association studies have identified >230 IBD loci, there have been a limited number of studies investigating sex differences underlying these genetic associations.

Genetic coding variant in complement factor B (CFB) is associated with increased risk for perianal Crohn's disease and leads to impaired CFB cleavage and phagocytosis.

Objective: Perianal Crohn's disease (pCD) occurs in up to 40% of patients with CD and is associated with poor quality of life, limited treatment responses and poorly understood aetiology. We performed a genetic association study comparing CD subjects with and without perianal disease and subsequently performed functional follow-up studies for a pCD associated SNP in ().

Design: Immunochip-based meta-analysis on 4056 pCD and 11 088 patients with CD from three independent cohorts was performed.

Magnetic resonance imaging for characterization of hepatocellular carcinoma metabolism.

With a better understanding of the pathophysiological and metabolic changes in hepatocellular carcinoma (HCC), multiparametric and novel functional magnetic resonance (MR) and positron emission tomography (PET) techniques have received wide interest and are increasingly being applied in preclinical and clinical research. These techniques not only allow for non-invasive detection of structural, functional, and metabolic changes in malignant tumor cells but also characterize the tumor microenvironment (TME) and the interactions of malignant tumor cells with the TME, which has hypoxia and low pH, resulting from the Warburg effect and accumulation of metabolites produced by tumor cells and other cellular components. The heterogeneity and complexity of the TME require a combination of images with various parameters and modalities to characterize tumors and guide therapy.