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Inflammatory bowel disease (IBD) is a chronic systemic inflammatory condition regarded as a major risk factor for colitis-associated cancer. However, the underlying mechanisms of IBD remain unclear. First, five GSE data sets available in GEO were used to perform 'batch correction' and Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs). Candidate molecules were identified using CytoHubba, and their diagnostic effectiveness was predicted. The CIBERSORT algorithm evaluated the immune cell infiltration in the intestinal epithelial tissues of patients with IBD and controls. Immune cell infiltration in the IBD and control groups was determined using the least absolute shrinkage selection operator algorithm and Cox regression analysis. Finally, a total of 51 DEGs were screened, and nine hub genes were identified using CytoHubba and Cytoscape. GSE87466 and GSE193677 were used as extra data set to validate the expression of the nine hub genes. CD4-naïve T cells, gamma-delta T cells, M1 macrophages and resting dendritic cells (DCs) are the main immune cell infiltrates in patients with IBD. Signal transducer and activator of transcription 1, CCR5 and integrin subunit beta 2 (ITGB2) were significantly upregulated in the IBD mouse model, and suppression of ITGB2 expression alleviated IBD inflammation in mice. Additionally, the expression of ITGB2 was upregulated in IBD-associated colorectal cancer (CRC). The silence of ITGB2 suppressed cell proliferation and tumour growth in vitro and in vivo. ITGB2 resting DCs may provide a therapeutic strategy for IBD, and ITGB2 may be a potential diagnostic marker for IBD-associated CRC.
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Biologia Computacional , Doenças Inflamatórias Intestinais , Humanos , Animais , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Biologia Computacional/métodos , Camundongos , Perfilação da Expressão Gênica , Modelos Animais de Doenças , Antígenos CD18/genética , Antígenos CD18/metabolismo , Mapas de Interação de Proteínas , Receptores CCR5/genética , Receptores CCR5/metabolismoRESUMO
Background and Objective: The study of resilience in youth with inflammatory bowel disease (IBD) is in early stages. The current review aims to illustrate how the use of a multisystemic framework may serve as a developmental and disease-appropriate framework for conceptualizing and designing resilience research for youth with IBD. Methods: This is a narrative review; therefore, a comprehensive and systematic literature search was not conducted. Rather, the current paper aims to map selected existing literature to a multisystemic model as exemplars of how the model may be used in youth with IBD. Relevant literature was reviewed, synthesized, and mapped onto the proposed multi-systemic framework. Key Content and Findings: The current review considers existing literature across three proposed dimensions of resilience: contexts of risk exposure, protective and promotive factors/processes, and desired outcomes. Review of each dimension includes consideration of selected existing literature to explain what is known about each dimension currently, as well as to propose additional potential future areas to broaden understanding. Specific key takeaways include: (I) understanding risk exposure in young people with IBD requires consideration of disease-specific, demographic, and sociocultural factors; (II) protective and promotive factors and processes for these young people span individual, familial, peer, school, and community levels; and (III) desired outcomes encompass both the absence of negative and the presence of positive indicators. Conclusions: A multisystemic approach to the study of resilience in young people with IBD may not only clarify current gaps in the field, but also allow for additional future considerations to best understand how and for whom outcomes characterized as resilient may occur in this population.
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The perianal disease affects up to one-third of individuals with Crohn's disease (CD), causing disabling symptoms and significant impairment in quality of life, particularly for those with perianal fistulising CD (PFCD). The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing. Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents, endoscopic procedures and surgical techniques that show promising results. Among these, mesenchymal stem cells injection is a particularly hopeful therapy. In addition to the burden of fistulas, individuals with perianal CD may face an increased risk of developing anal cancer. This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes. Currently, there is no established formal anal screening programme. In this review, we provide an overview of the current state of the art in managing PFCD, including novel medical, endoscopic and surgical approaches. The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD, intending to propose a risk-based surveillance algorithm. The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.
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Neoplasias do Ânus , Doença de Crohn , Detecção Precoce de Câncer , Fístula Retal , Humanos , Neoplasias do Ânus/terapia , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/patologia , Fístula Retal/terapia , Fístula Retal/etiologia , Fístula Retal/diagnóstico , Fístula Retal/epidemiologia , Doença de Crohn/terapia , Doença de Crohn/diagnóstico , Doença de Crohn/complicações , Doença de Crohn/epidemiologia , Detecção Precoce de Câncer/métodos , Qualidade de Vida , Canal Anal/cirurgia , Canal Anal/patologia , Fatores de RiscoRESUMO
Background: The risk of serious infection and active tuberculosis in patients with inflammatory bowel disease (IBD) has not been concurrently evaluated based on the use of anti-tumor necrosis factor (TNF)-α agents versus non-anti-TNF biologics (vedolizumab/ustekinumab) in the Korean population. Objectives: We compared the risk of serious infection and active tuberculosis in Korean patients with IBD treated with non-anti-TNF biologics (vedolizumab/ustekinumab) or anti-TNF-α agents. Design: This study was a population-based cohort analysis of nationwide administrative claims data. Methods: Health Insurance Review and Assessment Service claims data (representing 97% of the South Korean population) from between January 2007 and February 2021 were reviewed, and adults with IBD who initiated vedolizumab/ustekinumab or anti-TNF-α treatment (n = 6123) between 2017 and 2020 were enrolled. Intergroup differences in the risk of serious infection requiring hospitalization/emergency department visits or active tuberculosis during the follow-up period were analyzed. Results: In the patients treated with anti-TNF-α agents or vedolizumab/ustekinumab during a mean follow-up of 1.55 ± 1.05 and 0.84 ± 0.69 years, the incidence rates of serious infection were 9.43/100 and 6.87/100 person-years, respectively. Multivariable analysis showed no significant intergroup difference in the risk of serious infection with vedolizumab/ustekinumab or anti-TNF-α treatment; the adjusted relative risk of vedolizumab/ustekinumab compared with anti-TNF-α agents was 0.81 (95% confidence interval 0.46-1.44, p = 0.478). Among patients treated with anti-TNF-α agents and vedolizumab/ustekinumab, the incidence rates of active tuberculosis were 0.87 and 0.37 per 100 person-years, respectively. The relative risk of vedolizumab/ustekinumab compared with anti-TNF-α agents was 0.31 (95% confidence interval 0.07-1.26, p = 0.101). In a subset analysis comparing vedolizumab and ustekinumab with anti-TNF-α agents, similar results were observed. Conclusion: In Korean patients with IBD, non-anti-TNF biologics (vedolizumab/ustekinumab) tended to be associated with a lower risk of serious infection or active tuberculosis than anti-TNF-α agents.
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Background: Patients with inflammatory bowel disease (IBD) are often faced with distressing and confusing abdominal pain during remission. Some people respond adversely to healthcare professionals' (HCPs) suggestions that this pain and related symptoms are due to secondary irritable bowel syndrome (IBS). Exploring how HCPs view, manage, and explain pain during quiescent disease may provide insights into how communication can be improved to increase understanding and mitigate negative responses. Methods: In-depth semi-structured interviews were conducted with 12 IBD-nurses (n = 4) and gastroenterologists (n = 8) working in the United Kingdom or the Netherlands. Reflexive thematic analysis was used to analyse interviews. Results: Findings suggest that HCPs pay relatively little attention to pain when there is no underlying pathology and prefer to concentrate on objectifiable causes of symptoms and treating disease activity (Theme 1: Focus on disease activity, not pain and associated symptoms). Explanations of abdominal pain and IBS-like symptoms during remission were not standardised (Theme 2: Idiosyncratic and uncertain explanations for pain during remission). Processes of shared decision-making were outlined and shared sensemaking was reported as a strategy to enhance acceptance of IBS explanations (Theme 3: Shared decision making versus shared sensemaking). Conclusion: Future work should focus on establishing how pain during remission may be best defined, when to diagnose IBS in the context of IBD, and how to explain both to patients. The formulation of standardised explanations is recommended as they might help HCPs to adopt practices of shared sensemaking and shared decision-making. Explanations should be adaptable to specific symptom presentations and different health literacy levels.
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OBJECTIVES: This meta-analysis aimed to ascertain whether small molecule drugs increase the risk of infection or malignancy in adult IBD patients. METHODS: A comprehensive search of eight databases was conducted from their inception to November 2023. The risk of infections or malignancies in adult IBD patients treated with JAK inhibitors and S1P receptor modulators was compared. Fixed-effects or random-effects models were performed, and relative risk (RR) and 95 % confidence interval (CI) were calculated. RESULTS: 27 RCTs from 14 studies were included (n = 10,623). The evidence indicates that small molecule drugs increase the risk of any infections (RR: 1.23, 95 %CI: 1.05-1.44) and herpes zoster (RR: 2.23, 95 %CI: 1.39-3.57). Specifically, UC patients on Filgotinib and Tofacitinib, and CD patients on Upadacitinib, showed elevated risks of any infections (RR: 1.27, 95 % CI: 1.04-1.56; RR: 1.42, 95 % CI: 1.16-1.75; RR: 1.57, 95 % CI: 1.11-2.22). CD patients on Upadacitinib also had a significantly higher risk of herpes zoster (RR: 2.64, 95 %CI: 1.16-5.99). No infections were associated with S1P receptor modulators, and similarly, no malignancies were linked to small molecule drugs. CONCLUSIONS: JAK inhibitors increase the risk of any infections and herpes zoster Over a one-year follow-up period in IBD patients. Continuous monitoring of their long-term safety is necessary.
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BACKGROUND: In inflammatory bowel disease (IBD) of humans, nutrient malabsorption can result in fat-soluble vitamin deficiency, especially of vitamin D. In veterinary species, decreased concentrations of vitamin D are relatively common in dogs with chronic enteropathy (CE), but data on the status of other fat-soluble vitamins (FSVs) is lacking. OBJECTIVES: Determine the serum concentrations of retinol, vitamin D, and α-tocopherol in dogs with CE compared with healthy dogs and compare clinical, clinicopathologic variables between CE and healthy dogs to detect associations with decreased FSVs concentrations. ANIMALS: Eighteen client-owned dogs with CE and 33 healthy dogs. METHODS: Serum 25-hydroxyvitamin D (25[OH]D), serum retinol and α-tocopherol concentrations were compared between groups. Correlations and multiple regression modeling were used to examine the relationship between serum 25(OH)D, retinol, and α-tocopherol concentrations and clinical and clinicopathological variables. RESULTS: Dogs with low serum albumin concentrations were more likely to have lower 25(OH)D concentrations than dogs with normal serum albumin concentration. Dogs with CE had higher serum concentrations of retinol, and variable α-tocopherol concentrations. The cause of these dysregulated vitamin concentrations is unclear and requires further study. CONCLUSION AND CLINICAL IMPORTANCE: Dogs with severe forms of CE should be monitored for decreased concentrations of 25(OH)D. Additional studies are needed to evaluate the clinical relevance and the possible benefit of vitamin D supplementation in these patients.
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PURPOSE: To present the main findings of a post-authorization safety study assessing pregnancy and infant outcomes after prenatal golimumab exposure in a real-world setting. METHODS: This observational population-based cohort study included data from pregnancies ending in 2006-2018 (Finland) or 2019 (Denmark, Sweden). Infants born to women with rheumatic diseases or ulcerative colitis diagnoses were identified. Based on prescription fills from 90 days prior to pregnancy until delivery, infants were assigned to one of the four drug-exposure cohorts: golimumab, other anti-TNF biologics, other biologics, and nonbiologic systemic therapy, and the general population. Prevalence of adverse pregnancy outcomes, mortality, diagnoses of major congenital anomalies (MCA), and inpatient infections in the infants' first year of life were assessed. Odds ratios and 95% CIs were calculated for MCA and infection. RESULTS: Among 134 infants in the golimumab cohort, none were stillborn or died in the first year of life. MCA were diagnosed in 4.5% of the infants in the golimumab cohort, versus 6.8%, 10.9%, 5.5%, and 4.6% in the other anti-TNF biologics, other biologics, nonbiologic systemic therapy and general population cohorts, respectively. Inpatient infections were diagnosed in 11% of golimumab-exposed infants, compared with 9%-11% of infants in the other cohorts. Unadjusted and selected adjusted comparisons showed no association between prenatal golimumab exposure and MCA or infection compared with the other exposure cohorts or general population. CONCLUSIONS: The number of infants with prenatal golimumab exposure was low, but results are reassuringly consistent with the evidence available for other anti-TNF biologics. Continued monitoring is needed.
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Anticorpos Monoclonais , Resultado da Gravidez , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Gravidez , Suécia/epidemiologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Recém-Nascido , Resultado da Gravidez/epidemiologia , Adulto , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Finlândia/epidemiologia , Lactente , Estudos de Coortes , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , Dinamarca/epidemiologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Anormalidades Induzidas por Medicamentos/epidemiologia , Adulto JovemRESUMO
OBJECTIVES: Pathology is an essential component of disease diagnosis and management in pediatric gastroenterology. Pathology reports have not been standardized in some areas of pediatric gastrointestinal pathology and pathology reporting varies. Development of electronic medical record (EMR) pathology synoptic report templates (PSRT) enables pathology data collection in a specific format and can help standardize pathology reporting. We developed, implemented, and evaluated EMR PSRTs for eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD). METHODS: PSRTs were developed by a multidisciplinary team of pediatric experts of allergy, gastroenterology, and pathology for both EoE and IBD based on available literature and validated scales. Likert surveys (range 1 low acceptance to 5 high acceptance) based on the Technology Acceptance Model assessed user acceptance of the developed PSRTs. The use of PSRTs was monitored via control charts. RESULTS: Overall, evaluation questionnaires achieved >80% response rates. Clinicians and pathologists reported moderate-to-high levels of Perceived Usefulness (median [interquartile range) for EoE PSRT: clinicians 4.0 (4.0, 5.0) and pathologists 3.5 (3.5, 4.0); and IBD PSRT: clinicians 4.0 (3.0, 4.0) and pathologists 4.0 (4.0, 5.0)) and Perceived Ease of Use (EoE PSRT: clinicians 4.5 (4.0, 5.0) and pathologists 4.0 (4.0, 4.0); and IBD PSRT: clinicians 4.0 (4.0, 5.0) and pathologists 4.0 (4.0, 5.0)) of the developed PSRTs. Control charts demonstrated 100% utilization by 2-5 months from launch. CONCLUSIONS: We demonstrate successful implementation of synoptic reporting for both pediatric EoE and IBD pathology. EMR synoptic reporting provides standardization of pathology reporting and improved methods of pathology data presentation, which could potentially optimize provider efficiency, clinician interpretation of pathology results and disease trajectory, patient care, and clinician satisfaction.
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BACKGROUND: Chronic non-bloody diarrhea may be attributed either to functional or organic diseases. The latter category may present with malabsorption syndrome if there is extensive involvement of the small bowel, whereas diseases of the large bowel may only present with diarrhea sans malabsorption. Indian data has predominantly focussed on the etiological spectrum of malabsorption syndrome in adults. The primary aim of the current study was to evaluate etiological spectrum of chronic organic non-bloody diarrhea in India. METHODS: This prospective observational study was done at a tertiary care hospital in North India. Patients ≥ 18 years presenting with chronic non-bloody diarrhea of > 4 weeks duration were enrolled in the study after exclusion of patients with IBS and anal incontinence. RESULTS: During the study period of 12 months, 100 patients with chronic organic non-bloody diarrhea were evaluated. A definite etiological diagnosis was made in 97 patients (97%). The mean age of the patients was 48 ± 16.7 years (58% males). The median duration of diarrhea was 5.5 months (interquartile range [IQR] 3.5, 11). Inflammatory bowel disease (IBD) accounted for 45% of the cases making it the predominant cause for organic diarrhea. GI infections and adult-onset celiac disease accounted for 18% and 9% of the cases, respectively. Pancreatic disease, benign or neoplastic, accounted for 6% of the total cases. Notably, gastrointestinal (GI) malignancies manifesting as chronic non-bloody diarrhea were diagnosed in 5% of the patients. CONCLUSION: Our data suggests a paradigm shift in the etiological spectrum of chronic organic non-bloody diarrhea in India with the emergence of IBD as the predominant cause displacing GI infections.
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In this editorial, we comment on the article by Stafie et al. Inflammatory bowel disease (IBD) constitutes a cluster of chronic and progressive inflammatory disorders affecting the digestive system. IBD can impede an individual's capacity to perform daily activities, hinder work productivity, limit physical capabilities, and negatively impact medical outcomes. Although physical activity and structured exercise programs are becoming increasingly important in many chronic inflammatory diseases, they are not being sufficiently implemented in IBD patients. Effective prevention of future disability and drug dependence in IBD patients requires timely diagnosis and treatment of musculoskeletal problems, including sarcopenia, as well as decreased muscle strength, aerobic capacity, and bone mineral density. To improve treatment outcomes for IBD patients, it is crucial to develop individualized rehabilitation programs tailored to their unique needs. Equally critical is the active participation of pertinent departments in this process. It is imperative to highlight the significance of creating a personalized rehabilitation program with a multidisciplinary approach in IBD management.
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Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/reabilitação , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/fisiopatologia , Terapia por Exercício/métodos , Resultado do Tratamento , Atividades Cotidianas , Sarcopenia/reabilitação , Sarcopenia/diagnóstico , Sarcopenia/fisiopatologia , Exercício Físico , Força Muscular , Qualidade de VidaRESUMO
The concept of inflammatory bowel disease (IBD), which encompasses Crohn's disease and ulcerative colitis, represents a complex and growing global health concern resulting from a multifactorial etiology. Both dysfunctional autophagy and dysbiosis contribute to IBD, with their combined effects exacerbating the related inflammatory condition. As a result, the existing interconnection between gut microbiota, autophagy, and the host's immune system is a decisive factor in the occurrence of IBD. The factors that influence the gut microbiota and their impact are another important point in this regard. Based on this initial perspective, this manuscript briefly highlighted the intricate interplay between the gut microbiota, autophagy, and IBD pathogenesis. In addition, it also addressed the potential targeting of the microbiota and modulating autophagic pathways for IBD therapy and proposed suggestions for future research within a more specific and expanded context. Further studies are warranted to explore restoring microbial balance and regulating autophagy mechanisms, which may offer new therapeutic avenues for IBD management and to delve into personalized treatment to alleviate the related burden.
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Autofagia , Disbiose , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/imunologia , Disbiose/imunologia , Doença de Crohn/microbiologia , Doença de Crohn/imunologia , Colite Ulcerativa/microbiologia , Colite Ulcerativa/imunologia , Animais , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/imunologiaRESUMO
Inflammatory bowel disease (IBD) is the consequence of a complex interplay between environmental factors, like dietary habits, that alter intestinal microbiota in response to luminal antigens in genetically susceptible individuals. Epigenetics represents an auspicious area for the discovery of how environmental factors influence the pathogenesis of inflammation, prognosis, and response to therapy. Consequently, it relates to gene expression control in response to environmental influences. The increasing number of patients with IBD globally is indicative of the negative effects of a food supply rich in trans and saturated fats, refined sugars, starches and additives, as well as other environmental factors like sedentarism and excess bodyweight, influencing the promotion of gene expression and increasing DNA hypomethylation in IBD. As many genetic variants are now associated with Crohn's disease (CD), new therapeutic strategies targeting modifiable environmental triggers, such as the implementation of an anti-inflammatory diet that involves the removal of potential food antigens, are of growing interest in the current literature. Diet, as a strong epigenetic factor in the pathogenesis of inflammatory disorders like IBD, provides novel insights into the pathophysiology of intestinal and extraintestinal inflammatory disorders.
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Metilação de DNA , Dieta , Epigênese Genética , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/imunologia , Dieta/efeitos adversos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Doença de Crohn/genética , Doença de Crohn/imunologia , Comportamento Alimentar , Predisposição Genética para DoençaRESUMO
Purpose: There is scarce evidence to support the effectiveness of faecal microbiota transplantation (FMT) in improving sleep among individuals with inflammatory bowel disease (IBD). Our study aimed to evaluate the effect of washed microbiota transplantation (WMT) (the new method of FMT) on the sleep of patients with IBD in short term. Patients and Methods: This prospective study was conducted as part of two interventional clinical trials (starting on February 2013 and expected to end on December 2025) and placed significant emphasis on evaluating sleep quality in patients with IBD. To measure subjective sleep, we used the Pittsburgh sleep quality index (PSQI). The primary endpoint was the PSQI score one month after WMT. Results: This stage study included 52 eligible patients evaluated by PSQI questionnaire who underwent WMT from January 2020 to March 2021 and 47 patients were enrolled for analysis. The age of the patients ranged from 13 to 60 years, with a mean of 33.4 years, and 57.4% (25/47) of the patients were male. The PSQI scores for all 47 patients one month after undergoing WMT were significantly lower (Cohen d = 0.59, p < 0.001) compared to the baseline. Moreover, baseline PSQI score was correlated with the difference value of the PSQI score before and after WMT (post-PSQI minus pre-PSQI) (r = 0.61, p < 0.05). Conclusion: The study suggests that WMT might be a helpful intervention for improving the sleep quality of patients with IBD, encouraging clinicians to consider its use in clinical practice for addressing poor sleep in IBD patients. Clinical Trial Registration: ClinicalTrials.gov; ID: NCT01793831, NCT01790061.
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Objective: This Mendelian Randomization (MR) study aims to explore the potential bidirectional causal relationship between Inflammatory Bowel Disease (IBD) and Breast Cancer (BC). Materials and Methods: We utilized genetic instruments from the summary statistics of genome-wide association studies (GWAS) on IBD among individuals of European ancestry (12,882 cases and 21,770 controls) to investigate the association with breast cancer (14,910 cases and 17,588 controls) and vice versa. The primary causal estimates were obtained using the Inverse Variance Weighting Method (IVW), and the robustness of the results was evaluated through a series of sensitivity analyses. Results: The study found a positive impact of genetically predicted IBD on breast cancer (OR = 1.047; 95% CI:1.009-1.087; p = 0.014); in the analysis of IBD subtypes, genetically predicted Crohn's Disease (CD) also had a positive effect on breast cancer (OR = 1.044; 95% CI:1.015-1.073; p = 0.002), but genetically predicted Ulcerative Colitis (UC) did not show a significant effect on breast cancer (p > 0.05). The reverse Mendelian Randomization analysis indicated that genetically predicted breast cancer promoted the overall occurrence of IBD (OR = 1.112; 95% CI:1.022-1.211; p = 0.014); however, genetically predicted breast cancer did not show a significant correlation with IBD subtypes (CD and UC) (p > 0.05). Genetic predictions indicate a positive effect of Crohn's Disease (CD) on the risk of Estrogen Receptor-Positive Breast Cancer (ER + BC), with (OR = 1.021; 95% CI:1.002-1.040; p = 0.002). Furthermore, a reverse Mendelian randomization analysis reveals that genetically predicted ER + BC contributes to the increased incidence of ulcerative colitis (UC), as indicated by (OR = 1.098; 95% CI:1.032-1.168; p = 0.003). In contrast, genetically predicted Estrogen Receptor-Negative Breast Cancer (ER-BC) has been shown to promote the overall occurrence of inflammatory bowel disease (IBD), with (OR = 1.153; 95% CI:1.008-1.319; p = 0.037). However, bidirectional two-sample Mendelian randomization analyses between other pairs did not reveal any significant associations (p > 0.05). Conclusion: This study elucidates the bidirectional causal association between breast cancer and inflammatory bowel disease, highlighting the necessity of screening for IBD in breast cancer patients and for breast cancer in IBD patients in clinical settings.
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BACKGROUND: An inverse relationship exists between inflammation and testosterone concentrations in non-inflammatory bowel disease (IBD) immune conditions but has not been objectively explored in the IBD male population. We aimed to characterize the distribution of testosterone concentrations in a cohort of males with IBD and identify any relationship between testosterone levels and disease activity. METHODS: We conducted a prospective cross-sectional study of male IBD patients. Demographics, disease characteristics, sex-hormone concentration, gonadotropins, C-reactive protein, fecal calprotectin, and patient-reported outcomes on quality of life and erectile function were collected. Relationships between disease activity, biomarkers, patient-reported outcome scores, and testosterone levels were analyzed using univariate and multivariate linear regression analyses. RESULTS: A total of 85 male IBD patients were included with a mean age 44 ± 14.1 years, of which 49.4% had Crohn's disease. Mean testosterone concentration was 15.4 ± 5.2 nmol/L and 17.6% had a serum testosterone <10.4 nmol/L. Active disease was associated with lower testosterone concentrations in univariate analysis (ß ± SEâ =â -0.25 ± -1.99, Pâ =â .02) but not in multivariate analysis (ß -0.18 ± 1.75, Pâ =â .06). Testosterone concentrations were independently associated with sex hormone-binding globulin levels (ß ± SEâ =â 0.45 ± 0.04, P < .0001) and a younger age (ß ± SEâ =â -0.32 ± 0.04, P <.0001). Erectile function scores (5-item International Index of Erectile Function) were lower in IBD patients with a longer duration of disease (ß ± SEâ =â -0.24 ± 0.006, Pâ =â .04). CONCLUSIONS: Lower testosterone concentrations in men with IBD may reflect confounding from other factors and are not independently associated with disease activity. Greater awareness and screening for sexual dysfunction should occur in males with IBD, particularly in those with a longer disease duration.
Sexual dysfunction in men with inflammatory bowel disease (IBD) is multifactorial. We explored the underlying hormonal profile of men with IBD and characterized the distribution of testosterone levels. Almost 1 in 5 males with IBD have a level that is considered low by international definitions (<10.4 nmol/L).
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Inflammatory bowel disease (IBD) is a refractory disease with immune abnormalities and pathological changes. Intestinal macrophages are considered to be the main factor in establishing and maintaining intestinal homeostasis. The immunoregulatory and anti-inflammatory activity of fibrinogen-like protein 2 (FGL2) can regulate macrophage polarization. However, its function in IBD is unclear. In this study, we explored the effect of FGL2 on macrophage polarization, autophagy, and apoptosis in bone marrow-derived macrophages (BMDMs) treated with lipopolysaccharide (LPS) and further investigated changes in the intestinal barrier, flora, and bile acid in dextran sodium sulfate (DSS)-treated mice. Our results demonstrated that FGL2-/- weakened ERK signaling to promote M1 polarization and upregulate inflammation, autophagy, and apoptosis in LPS-stimulated BMDMs. rFGL2 treatment reversed these effects. FGL2-/- mice exhibited higher sensitivity to DSS exposure, with faster body weight loss, shorter colon lengths, and higher disease activity index (DAI) values. rFGL2 treatment protected against experimental ulcerative colitis (UC), restrained excessive autophagy, apoptosis, and improved gut barrier impairment. Gut microbiota structure and bile acid homeostasis were more unbalanced in FGL2-/- DSS mice than in wild-type (WT) DSS mice. rFGL2 treatment improved gut microbiota structure and bile acid homeostasis. Altogether, our results established that FGL2 is a potential therapeutic target for IBD.
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Inflammatory bowel disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract, often leading to symptoms like abdominal pain and diarrhea. Given the increasing evidence linking systemic inflammation to atrial fibrillation development, investigating IBD as a potential risk factor for atrial fibrillation becomes imperative. This meta-analysis aims to evaluate the impact of atrial fibrillation on inpatient outcomes, resource utilization, and length of hospital stays among IBD patients. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines, a systematic literature search was conducted across multiple databases, including Embase, PubMed, Scopus, and Web of Science, from the inception of databases to June 5, 2024. Eligible studies included prospective or retrospective studies with definitive diagnoses of ulcerative colitis, Crohn's disease, or IBD, demonstrating the influence of atrial fibrillation. Data were extracted, and quality assessment was performed using the Newcastle-Ottawa Scale. The meta-analysis comprised 842,149 IBD patients, with 71,221 having atrial fibrillation. Pooled analysis revealed a significant association between atrial fibrillation and heightened all-cause mortality risk (risk ratio (RR): 1.42, 95% confidence interval (CI): 1.16 to 1.74, p<0.01). However, no significant differences were observed in the incidence of acute myocardial infarction, acute kidney injury, or acute respiratory failure between patients with and without atrial fibrillation. IBD patients with comorbid atrial fibrillation face higher mortality rates, potentially due to systemic inflammation, thromboembolism risks, polypharmacy, and the complexities of managing both conditions concurrently. Early identification and integrated management of atrial fibrillation in IBD patients are crucial to improving outcomes. Larger, multi-center studies are needed to explore the underlying mechanisms and develop tailored treatment strategies.
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BACKGROUND AND OBJECTIVE: Probiotics show promise in inflammatory bowel disease (IBD), yet knowledge gaps persist. We performed an overview of systematic reviews and an updated metanalysis of randomized controlled trials (RCT) assessing the effect of probiotics on Crohn's disease (CD) and ulcerative colitis (UC). METHODS: MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched up to September 2023. Primary outcomes were clinical remission and recurrence; secondary outcomes included endoscopic response and remission, and adverse events. We calculated odds ratios (OR) using a random-effects model in R. The quality of systematic reviews was assessed using the AMSTAR-2; the trials' risk of bias was evaluated using the Cochrane Collaboration tool. Evidence certainty was rated using the GRADE framework. RESULTS: Out of 2613 results, 67 studies (22 systematic reviews and 45 RCTs) met the eligibility criteria. In the updated meta-analysis, the OR for clinical remission in UC and CD was 2.00 (95% CI 1.28-3.11) and 1.61 (95% CI 0.21-12.50), respectively. The subgroup analysis suggested that combining 5-ASA and probiotics may be beneficial for inducing remission in mild-to-moderate UC (OR 2.35, 95% CI 1.29-4.28). Probiotics decreased the odds of recurrence in relapsing pouchitis (OR 0.03, 95% CI 0.00-0.25) and trended toward reducing clinical recurrence in inactive UC (OR 0.65, 95% CI 0.42-1.01). No protective effect against recurrence was identified for CD. Multi-strain formulations appear superior in achieving remission and preventing recurrence in UC. The use of probiotics was not associated with better endoscopic outcomes. Adverse events were similar to control. However, the overall certainty of evidence was low. CONCLUSION: Probiotics, particularly multi-strain formulations, appear efficacious for the induction of clinical remission and the prevention of relapse in UC patients as well as for relapsing pouchitis. Notwithstanding, no significant effect was identified for CD. The favorable safety profile of probiotics was also highlighted.