Inflammatory bowel disease (IBD) is a chronic heterogeneous group of diseases that has undergone major advances in the understanding of its etiology and pathogenesis in recent years. The development ...of biologics had resulted in better overall management of the disease, including lower rates of surgery and better long-term clinical and patient-reported outcomes. Treatment modalities have either been newly developed or extrapolated from their approved use for a different indication. Modes of action and treatment targets have varied as well. Treatments such as vedolizumab and ustekinumab, as well as second-generation corticosteroids have been approved by the US Food and Drug Administration (FDA) for the treatment of IBD. Other agents are currently being developed at various stages of clinical trials including anti-adhesion agents such as etrolizumab and abrilumab, JAK inhibitors such as tofacitinib, and anti-trafficking molecules. Toll-like receptors and phosphatidylcholine are also new promising emerging targets that are being investigated in phase 3 clinical trials. It is projected that many therapies will become available in the coming years if supported by the results of current clinical trials. This will provide IBD patients with a wide array of options and allow physicians to choose the best therapies for each individual patient.
Overview to Challenges in IBD 2024-2029 Heller, Caren; Moss, Alan C; Rubin, David T
Inflammatory bowel diseases,
05/2024, Letnik:
30, Številka:
Supplement_2
Journal Article
Recenzirano
Odprti dostop
The mission of the Crohn's & Colitis Foundation is to cure Crohn's disease and ulcerative colitis and to improve the quality of lives of patients living with these diseases-in other words, to care ...and cure. To achieve these missions, there is a need to identify and prioritize research gaps and approaches to address these gaps, which is the aim of Challenges in IBD 2024. The Foundation convened close to 80 experts in inflammatory bowel disease (IBD), including researchers, clinicians, patients and caregivers, funders, industry representatives, and Foundation scientific staff and organized them into 5 workgroups, one for each of the 5 Challenges topics: Preclinical Human IBD Mechanisms, Environmental Triggers, Precision Medicine, Novel Technologies, and Pragmatic Clinical Research. The findings of these groups outline a research agenda that intends to change the research paradigm in IBD by introducing 2 concepts in the course of IBD that warrant specific focus: interception (during the preclinical phase) and restoration of normal physiology after remission is achieved. We hope these reviews will stimulate innovations in our understanding and management of IBD.
The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced ...the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term “chromoplexy,” frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis.
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► Interdependent DNA rearrangements may coordinately remodel prostate cancer genomes ► “Chromoplexy” defines a distinct class of complex structural rearrangements ► Multiple prostate cancer genes may be dysregulated coordinately ► Clonal evolution reveals paths of prostate cancer progression
Modeling the genesis of chromosomal rearrangements in prostate cancer genomes reveals that the chromosomal disarray found in a typical tumor may arise via a handful of discrete “chromoplexy” events during tumor development in which interdependent rearrangements shuffle DNA from five or more chromosomes.
Fecal calprotectin (Fcal) is a non-invasive and inexpensive biomarker of disease activity, however, patient compliance with this test is variable and incompletely described. Demographic, clinical, ...disease-related, and test-related (location of lab relative to the patient’s visit in clinic or at home) information were recorded to determine predictors for non-compliance. Linear Regressions for Predictors of Fecal Calprotectin Compliance Logistic Regression for Test Compliance Regression for Delayed Testing Completion Estimate Effect Size (B) Standard Error P - Value 95% Confidence Interval Estimate Effect Size (B) Standard Error P - Value 95% Confidence Interval Age 0.017 0.015 0.248 0.998-1.048 0.148 0.104 0.163 -31.309-7.575 Gender -0.441 0.543 0.417 0.222-1.866 0.877 3.635 0.810 0.062-0.357 IBD Remission -0.949 0.624 0.128 0.114-1.316 -0.331 3.895 0.933 -6.421-8.176 Consultation Type -.0523 0.528 0.322 0.210-1.570 0.102 3.992 0.980 -8.151-7.490 History of Fecal Calprotectin Completion 2.116 0.741 0.004 1.942-35.493 6.628 2.625 0.357 -7.699-20.956 Fecal Calprotectin Testing Location -1.304 0.668 0.51 0.073-1.005 12.875 3.843 0.002 5.160-20.591
Abstract
First detected in Wuhan, China, the novel 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus responsible for an unprecedented, worldwide ...pandemic caused by COVID-19. Optimal management of immunosuppression in inflammatory bowel disease (IBD) patients with COVID-19 infection currently is based on expert opinion, given the novelty of the infection and the corresponding lack of high-level evidence in patients with immune-mediated conditions. There are limited data regarding IBD patients with COVID-19 and no data regarding early pregnancy in the era of COVID-19. This article describes a patient with acute severe ulcerative colitis (UC) during her first trimester of pregnancy who also has COVID-19. The case presentation is followed by a review of the literature to date on COVID-19 in regard to inflammatory bowel disease and pregnancy, respectively.
This article presents a patient with acute severe ulcerative colitis during her first trimester of pregnancy who tested positive for COVID-19. In this new COVID-19 era, this article discusses management of this patient and reviews the current literature.
L23 is a recognized cytokine involved in the pathogenesis of inflammatory bowel diseases (IBDs).
The first IL23-targeting agent that became available for clinical use in IBD was Ustekinumab, a ...monoclonal antibody that targets p40, a shared subunit of both IL23 and IL12.
Risankizumab (Skyrizi; Abbvie) is a humanized IgG1 monoclonal antibody which binds to the p19 subunit and therefore selectively inhibits IL23.
In June 2022, it was approved by the United States Food and Drug Administration for the treatment of moderately to severely active Crohn's disease (CD). Here, we describe the effectiveness and safety of risankizumab throughout the induction period in a real-world setting of a large tertiary center.
Poor sleep quality is associated with adverse health consequences. Sleep disturbances can impact the immune function and process of inflammation. The relationship between sleep quality and the ...inflammatory bowel disease (IBD) has not been well studied.
A prospective observational cohort study was performed to assess the correlation of the quality of sleep and disease activity in IBD. We used the Pittsburgh Sleep Quality Index (PSQI) to measure sleep quality. IBD disease activity was measured by using the Harvey-Bradshaw Index or Modified Mayo Score.
Forty-one patients were enrolled with mean age of 37 ± 15.4 years and 27 (66%) women. Abnormal PSQI was present in all 23 (100%) of the clinically active patients and in 13 (72%) of those with inactive disease (odds ratio = 2.8, P = 0.007). All 30 patients with histologic evidence of inflammation on recent ileocolonoscopy also had abnormal PSQI scores, which were independent of their clinical disease activity status. Only 6 of 11 patients with histologically quiescent disease had abnormal PSQI scores (odds ratio = 6.0, P < 0.0001). There was no difference in disease type, use of steroids, the presence of depression or anxiety, and body mass index between the patients with normal and abnormal sleep. An abnormal PSQI had a positive predictive value for histologic inflammatory activity of 83%.
Our data show a strong association between clinically active IBD and poor sleep quality and demonstrate that patients in clinical remission with abnormal sleep have a high likelihood of subclinical disease activity.
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