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Introduction: Expeditious initiation of biologic therapy is important in patients with inflammatory bowel disease (IBD). However, initiation of biologics in the outpatient setting may be delayed by various clinical, social, and financial variables., Aim: To evaluate the delay in initiation of an advanced therapy in IBD and to identify factors that contributed to this delay., Methods: This was a multi-center retrospective study. Outpatients who were initiated on a biologic therapy from 3/1/2019 to 9/30/20 were eligible for the study. Univariate and multivariate linear regression analyses were performed to identify variables associated with a delay in biologic treatment initiation. Delay was defined as the days from decision date (prescription placement) to first infusion or delivery of medication., Results: In total 411 patients (Crohn's disease, n = 276; ulcerative colitis, n = 129) were included in the analysis. The median [interquartile range-(IQR)] delay for all drugs was 20 [12-37] days (infliximab, 19 [13-33] days; adalimumab, 10 [5-26] days; vedolizumab, 21 [14-42] days; and ustekinumab, 21 [14-42] days). Multivariate linear regression analysis identified that the most important variables associated with delays in biologic treatment initiation was self-identification as Black, longer distance from treatment site, and lack of initial insurance coverage approval., Conclusion: There may be a significant delay in biologic treatment initiation in patients with IBD. The most important variables associated with this delay included self-identification as Black, longer distance from site, and lack of initial insurance coverage approval., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aims: Artificial intelligence-based computer-aided polyp detection (CADe) systems are intended to address the issue of missed polyps during colonoscopy. The effect of CADe during screening and surveillance colonoscopy has not previously been studied in a United States (U.S.) population., Methods: We conducted a prospective, multi-center, single-blind randomized tandem colonoscopy study to evaluate a deep-learning based CADe system (EndoScreener, Shanghai Wision AI, China). Patients were enrolled across 4 U.S. academic medical centers from 2019 through 2020. Patients presenting for colorectal cancer screening or surveillance were randomized to CADe colonoscopy first or high-definition white light (HDWL) colonoscopy first, followed immediately by the other procedure in tandem fashion by the same endoscopist. The primary outcome was adenoma miss rate (AMR), and secondary outcomes included sessile serrated lesion (SSL) miss rate and adenomas per colonoscopy (APC)., Results: A total of 232 patients entered the study, with 116 patients randomized to undergo CADe colonoscopy first and 116 patients randomized to undergo HDWL colonoscopy first. After the exclusion of 9 patients, the study cohort included 223 patients. AMR was lower in the CADe-first group compared with the HDWL-first group (20.12% [34/169] vs 31.25% [45/144]; odds ratio [OR], 1.8048; 95% confidence interval [CI], 1.0780-3.0217; P = .0247). SSL miss rate was lower in the CADe-first group (7.14% [1/14]) vs the HDWL-first group (42.11% [8/19]; P = .0482). First-pass APC was higher in the CADe-first group (1.19 [standard deviation (SD), 2.03] vs 0.90 [SD, 1.55]; P = .0323). First-pass ADR was 50.44% in the CADe-first group and 43.64 % in the HDWL-first group (P = .3091)., Conclusion: In this U.S. multicenter tandem colonoscopy randomized controlled trial, we demonstrate a decrease in AMR and SSL miss rate and an increase in first-pass APC with the use of a CADe-system when compared with HDWL colonoscopy alone., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Artificial intelligence (AI) is a quickly expanding field in gastrointestinal endoscopy. Although there are a myriad of applications of AI ranging from identification of bleeding to predicting outcomes in patients with inflammatory bowel disease, a great deal of research has focused on the identification and classification of gastrointestinal malignancies. Several of the initial randomized, prospective trials utilizing AI in clinical medicine have centered on polyp detection during screening colonoscopy. In addition to work focused on colorectal cancer, AI systems have also been applied to gastric, esophageal, pancreatic, and liver cancers. Despite promising results in initial studies, the generalizability of most of these AI systems have not yet been evaluated. In this article we review recent developments in the field of AI applied to gastrointestinal oncology., Competing Interests: Conflict-of-interest statement: All authors disclose no financial relationships relevant to this publication., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Glycolysis and mitochondrial respiration are essential for oligodendrocyte metabolism in both the developing and adult CNS. Based on recent reports on the effects of the proinflammatory cytokine IFN-γ on metabolism and on oligodendrocytes, we addressed whether IFN-γ may affect oligodendrocyte bioenergetics in ways relevant to CNS disease. Oligodendrocytes of mice treated with IFN-γ showed significant reductions in aerobic glycolysis and mitochondrial respiration. As expected, IFN-γ treatment led to the induction of STAT1 in oligodendrocytes indicating active signaling into these cells. To determine the direct effects of IFN-γ on oligodendrocyte metabolism, cultured oligodendrocytes were treated with IFN-γ in vitro, which resulted in suppression of glycolysis similar to oligodendrocytes of animals treated with IFN-γ in vivo. Mice lacking SHP-1, a key regulator of IFN-γ and STAT1 signaling in CNS glia, had high constitutive levels of STAT1 and decreased aerobic glycolysis and mitochondrial respiration rates relative to wild type mouse oligodendrocytes. Together, these data show that IFN-γ and SHP-1 control oligodendrocyte bioenergetics in ways that may relate to the role of this cytokine in CNS disease., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In this study, we investigated four patients who met the diagnostic criteria for overlapping systemic lupus erythematosus (SLE) and myasthenia gravis (MG) but responded differently to treatment. All patients were acetylcholine receptor (AChR) and antinuclear antibody positive at the time of SLE diagnosis. Two patients presented with SLE who have been effectively treated with cholinesterase inhibitors for MG. These patients developed SLE with photosensitivity, rash, and arthritis post thymectomy, which had been performed 29 years and 40 years earlier, respectively. Two other patients were found to have AChR antibodies and MG in the context on new-onset SLE. These subjects were responsive to hydroxychloroquine and immunosuppression but failed cholinesterase inhibitors. The evolution of these cases is relevant for the role of thymus in lupus pathogenesis during aging and for treatment selection in SLE-MG overlap patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Macrophages are common targets for infection and innate immune activation by many pathogenic viruses including the neurotropic Theiler's Murine Encephalomyelitis Virus (TMEV). As both infection and innate activation of macrophages are key determinants of viral pathogenesis especially in the central nervous system (CNS), an analysis of macrophage growth factors on these events was performed. C3H mouse bone-marrow cells were differentiated in culture using either recombinant macrophage colony stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), inoculated with TMEV (BeAn) and analyzed at various times thereafter. Cytokine RNA and protein analysis, virus titers, and flow cytometry were performed to characterize virological parameters under these culture conditions. GM-CSF-differentiated macrophages showed higher levels of TMEV viral RNA and proinflammatory molecules compared to infected M-CSF-differentiated cells. Thus, GM-CSF increases both TMEV infection and TMEV-induced activation of macrophages compared to that seen with M-CSF. Moreover, while infectious viral particles decreased from a peak at 12h to undetectable levels at 48h post infection, TMEV viral RNA remained higher in GM-CSF- compared to M-CSF-differentiated macrophages in concert with increased proinflammatory gene expression. Analysis of a possible basis for these differences determined that glycolytic rates contributed to heightened virus replication and proinflammatory cytokine secretion in GM-CSF compared to M-CSF-differentiated macrophages. In conclusion, we provide evidence implicating a role for GM-CSF in promoting virus replication and proinflammatory cytokine expression in macrophages, indicating that GM-CSF may be a key factor for TMEV infection and the induction of chronic TMEV-induced immunopathogenesis in the CNS., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We have previously described reduced myelination and corresponding myelin basic protein (MBP) expression in the central nervous system of Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1) deficient motheaten (me/me) mice compared with normal littermate controls. Deficiency in myelin and MBP expression in both brains and spinal cords of motheaten mice correlated with reduced MBP mRNA expression levels in vivo and in purified oligodendrocytes in vitro. Therefore, SHP-1 activity seems to be a critical regulator of oligodendrocyte gene expression and function. Consistent with this role, this study demonstrates that oligodendrocytes of motheaten mice and SHP-1-depleted N20.1 cells produce higher levels of reactive oxygen species (ROS) and exhibit corresponding markers of increased oxidative stress. In agreement with these findings, we demonstrate that increased production of ROS coincides with ROS-induced signaling pathways known to affect myelin gene expression in oligodendrocytes. Antioxidant treatment of SHP-1-deficient oligodendrocytes reversed the pathological changes in these cells, with increased myelin protein gene expression and decreased expression of nuclear factor (erythroid-2)-related factor 2 (Nrf2) responsive gene, heme oxygenase-1 (HO-1). Furthermore, we demonstrate that SHP-1 is expressed in human white matter oligodendrocytes, and there is a subset of multiple sclerosis subjects that demonstrate a deficiency of SHP-1 in normal-appearing white matter. These studies reveal critical pathways controlled by SHP-1 in oligodendrocytes that relate to susceptibility of SHP-1-deficient mice to both developmental defects in myelination and to inflammatory demyelinating diseases., (© 2015 Wiley Periodicals, Inc.)