Group Of Inflammatory Bowel Disease Patients Research Articles

The substantial role of sleep, stress and physical activity in persistent high levels of fatigue in patients with inflammatory bowel disease: A longitudinal trajectory study.

Fatigue is a common and burdensome problem for patients with inflammatory bowel disease (IBD). Previous studies lack insight into the individual variability in fatigue severity and course over time, and the characteristics of patients at risk of severe and persistent fatigue. This study aimed to identify distinct groups of IBD patients based on their level and course of fatigue over five years. Subsequently, we examined the relationship between these trajectories, patient characteristics and trajectories of perceived stress, sleep and physical activity. This longitudinal cohort study used prospectively collected data from the myIBDcoach telemedicine monitoring tool, including 320 IBD patients who completed three or more online consultations between 2016 and 2021. Latent class growth analyses were performed to identify distinct trajectories. We found five subgroups with distinct trajectories of fatigue, differing in level and course over time, with 33% of patients experiencing chronic stable and high levels of fatigue. Few differences in patient characteristics were found between trajectories, yet the chronic high fatigue subgroup was more likely to report persistent stable sleep problems, perceived stress, and little physical activity over time compared to the other groups. Distinct subgroups of IBD patients can be identified based on longitudinal fatigue trajectories. The relatively stable levels of fatigue, stress, sleep, and physical activity suggest that a one-time screening of patients on these topics may be sufficient to identify those at risk. Interventions aiming to reduce fatigue should target persistent stress, sleep problems, and low levels of physical activity.

Extracellular Vesicle-Enclosed Oxidative Stress- and Inflammation-Related microRNAs as Potential Biomarkers of Vitamin D Responsivity: A Pilot Study on Inflammatory Bowel Disease Patients with or without COVID-19.

The relationship between serum 25-hydroxyvitamin D (25(OH)D) levels, genomic response to vitamin D (Vit.D), and positivity to SARS-CoV-2 remains understudied. In this pilot study, during the follow-up of patients with Inflammatory Bowel Disease (IBD) and COVID-19, we investigated this issue by analyzing the molecular contents of serum extracellular vesicles (EVs) from six groups of IBD patients (n = 32), classified according to anti-SARS-CoV-2 status, 25(OH)D level, and Vit.D supplementation, by small RNA-seq. This analysis revealed differentially expressed miRNAs, PIWI-RNA, transfer RNA, small nucleolar RNAs, and protein-coding RNAs in the EVs obtained from these cohorts of IBD patients. Experimental validation evidenced a statistically significant increase in miR30d-5p, miR150-5p, Let-7f-5p, and Let-7a-5p in the anti-SARS-CoV-2-positive and low 25(OH)D and Vit.D supplemented groups with respect to the non-Vit.D supplemented group, indicating their responsiveness to Vit.D treatment. Bioinformatics analysis highlighted the regulation of these validated miRNAs by oxidative stress and inflammation, hallmarks of IBD and COVID-19. Our study reports an unprecedented panel of circulating EV-enclosed inflammation- and oxidative stress-related miRNAs, the potentiality of which, as biomarkers for Vit.D responsivity in IBD patients, needs to be explored in future studies on larger cohorts in order to allow clinicians to optimize current treatment strategies upon viral infection.

MiR-146a (rs2910164) Gene Polymorphism and Its Impact on Circulating MiR-146a Levels in Patients with Inflammatory Bowel Diseases.

MicroRNA-146a (miR-146a) has been involved in the pathophysiology of inflammatory bowel disease (IBD). However, the precise processes are still not entirely understood. Contradictory studies suggest that miR-146a expression could be influenced by the miR-146a rs2910164 C > G polymorphism. This case-control study aimed to investigate the association ofmiR-146a rs2910164 C > G gene polymorphism and its impact on circulating miR-146a expression levels in Egyptian IBD patients. We included 40 IBD patients and 30 matched healthy controls. Genotyping of miR-146a rs2910164 polymorphism and assessment of miR-146a expression level were done using quantitative real-time PCR in all participants. MiR-146a rs2910164 GG genotype and the G allele were reported in 47% and 70% of the IBD patient group, respectively. And they were associated with increased IBD risk. All the IBD patients with the CC genotype (100%) and most of those with the CG genotype (66.67%) had an inactive disease, while most IBD patients with the GG genotype (73.68%) had an active disease. The miR-146a expression level was the highest with the CC genotype and the lowest with the GG genotype. Also, miR-146a expression level decreased significantly in IBD patients than controls and with disease activity. Combined detection of fecal calprotectin with miR-146a expression level improved the diagnostic sensitivity and the negative predictive value in differentiating IBD patients with active disease from those inactive.Our study identified a strong association of miR-146a rs2910164 GG genotype and G allele with IBD-increased susceptibility and activity in the Egyptian population. The miR-146a rs2910164 polymorphism can reduce miR-146a expression levels in these patients as well. Further research on a larger sample size and different ethnic populations can be the key to progress in establishing this genetic association.

Association of selected adipokines with vitamin D deficiency in children with inflammatory bowel disease

BackgroundAdipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency.MethodsThe study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants.ResultsChildren with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines.ConclusionsWhether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.

Relative Frequency of Gastrointestinal Functional Disorders in Patients with Inflammatory Bowel Disease Based on Rome IV: A Case-Control Study.

Inflammatory bowel disease (IBD) is a digestive system ailment that causes significant bodily disruption. This problem may coexist with other digestive system illnesses. One of the diseases that reduces the quality of life and other disorders is functional dyspepsia (FD), the diagnosis of which is associated with unique limitations. In this study, we aim to investigate the relative frequency of FD in IBD patients and compare it with a healthy control group. In a case-control study, we selected a group of IBD patients and healthy controls, and all participants were prepared for a diagnosis of FD symptoms using ROME IV criteria. Data were analyzed and compared using Chi-square and t-test, and P ≤ 0.05 was considered significant. There were 100 IBD patients, including 91 with ulcerative colitis and 9 with Crohn's disease (mean age, 41.37 ± 13; 39 males, 61 females). Furthermore, 100 healthy control subjects (mean age, 44.23 ± 14; 38 males, 62 females) were analyzed. 10% of IBD patients met the criteria of FD, which was comparable with the controls (5, 5%) (P > 0.05). Some of the symptoms of irritable bowel syndrome (IBS) including abdominal pain (P = 0.01) and bowel movement (P = 0.02) were significantly higher in IBD patients than in non-IBD subjects. The symptoms of FD were not significantly greater in IBD patients compared to the control group, while IBS symptoms were significantly higher in IBD individuals, indicating a possible overlap of Rome IV IBS and FD.

Familial Mediterranean fever in Armenian children with inflammatory bowel disease.

Inflammatory bowel disease (IBD) and familial Mediterranean fever (FMF) are inflammatory diseases with complex interactions among genetic, immune, and environmental factors. FMF is a monogenic autoinflammatory disease, characterized by recurrent febrile attacks and polyserositis, and is manifested mainly in childhood. FMF is widespread in Armenia. There are reports on the concurrent occurrence of FMF and IBD. MEFV gene mutations may have a disease-modifying effect on IBD. We have investigated the frequency of MEFV mutations and FMF in Armenian children with IBD and their influence on the clinical course. A total of 69 untreated IBD patients under 18 years of age were enrolled: 52.1% (36) had ulcerative colitis (UC), 21.7% (15) had Crohn's disease (CD), and 26.0% (18) had unclassified colitis (IBD-U). The frequency of FMF among them was 36.2% (25/69), and MEFV mutations were identified in 53.6% (37/69). The highest rate of MEFV mutations and FMF was in UC patients (61.1% and 41.6% respectively). In all, 56.7% (21/37) of IBD patients with MEFV mutations had M694V mutated alleles, mainly in compound heterozygous and heterozygous states. There were no associations in the group of IBD patients with coexisting FMF (25), either between any MEFV mutation and type of IBD or coexistence of FMF. Overall, 36.0% (9/25) of them developed VEO IBD and carried mainly the M694V mutation. We concluded that the carrier frequency of MEFV mutations among Armenian pediatric IBD patients was rather high (53.6%), especially for UC. It was suggested that the MEFV gene is not necessarily a susceptibility gene but most likely modifies the course of IBD. MEFV genetic testing was recommended for Armenian pediatric IBD patients, especially for VEO UC and IBD-U, atypical IBD course, or resistance to the conventional treatment. They should also be asked for isolated febrile attacks, recurrent arthritis, and family history, even in the absence of FMF typical symptoms, to rule out FMF and its complications.

Prevalence and Clinical Impact of Immune-Mediated Inflammatory Diseases in Patients with Inflammatory Bowel Disease: Results from a Large Retrospective Observational Study.

(1) Background: Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders involving innate and adaptive immune responses. Despite primarily affecting the gut, recent insights highlight systemic implications, expanding our understanding beyond intestinal boundaries. (2) Methods: This retrospective multicentric study explored the association of IBD and immune-mediated inflammatory diseases (IMIDs) and the impact of concurrent IMIDs on the course of IBD. Clinical data were collected from consecutive medical records of patients with IBD. For assessing the impact of concurrent IMIDs, a control group of IBD patients without associated IMIDs was considered. (3) Results: Of 6589 IBD patients, 6.8% exhibited concomitant IMIDs. Notably, 79.8% of these patients had an aggressive disease course. Psoriasis, atopic dermatitis, and type 1 diabetes mellitus prevalence were lower in the IBD population than in the general population. Conversely, multiple sclerosis, primary sclerosing cholangitis, and pyoderma gangrenosum were more prevalent in IBD patients. Among the patients with a concomitant IMID, 79.8% had an aggressive disease course vs. 8.1% in the control group (p < 0.001). (4) Conclusions: This study underscores the frequency of IMIDs in IBD patients and their association with a more aggressive disease course. The recognition of concurrent IMIDs is crucial for comprehensive patient management, influencing therapeutic decisions and potentially improving outcomes.

Non-alcoholic fatty liver disease (NAFLD) and obesity in inflammatory bowel disease (IBD) patients in Gorgan.

According to the significance of extraintestinal symptoms in inflammatory bowel disease (IBD) patients and their connection with obesity, we aimed to investigate the prevalence of fatty liver in IBD patients of Sayyad Shirazi Hospital in Gorgan, Iran, in relation to obesity, anthropometric indicators and body image in these patients. Forty patients with IBD were recruited from all registered patients at the Golestan Research Center of Gastroenterology and Hepatology, following the specified inclusion and exclusion criteria. After obtaining written informed consent and filling in the questionnaire, the demographic and anthropometric indicators, and variables related to the disease were measured. The liver sonography was performed on all patients and graded by an expert radiologist. Data were analyzed using SPSS Version 16.0 statistical software at the significance level of 0.05. We showed no significant difference between the distribution of demographic and anthropometric indicators in different groups of IBD patients. However, we demonstrated that the inappropriate values of HDL (0.004) and high values of LDL (0.015) were associated with fatty liver in IBD patients. Our findings also showed that NAFLD was significantly associated with overweight and obesity among IBD patients (P = 0.003). Our findings showed the epidemiological burden of NAFLD in IBD patients. Since fatty liver was associated with obesity, it is recommended that IBD patients be screened for risk factors associated with NAFLD to prevent liver disease.

Common diagnostic biomarkers and molecular mechanisms of Helicobacter pylori infection and inflammatory bowel disease.

Helicobacter pylori (H. pylori) may be present in the intestinal mucosa of patients with inflammatory bowel disease (IBD), which is a chronic inflammation of the gastrointestinal tract. The role of H. pylori in the pathogenesis of IBD remains unclear. In this study, bioinformatics techniques were used to investigate the correlation and co-pathogenic pathways between H. pylori and IBD. The following matrix data were downloaded from the GEO database: H. pylori-associated gastritis, GSE233973 and GSE27411; and IBD, GSE3365 and GSE179285. Differential gene analysis was performed via the limma software package in the R environment. A protein-protein interaction (PPI) network of DEGs was constructed via the STRING database. Cytoscape software, through the CytoHubba plugin, filters the PPI subnetwork and identifies Hub genes. Validation of the Hub genes was performed in the validation set. Immune analysis was conducted via the CIBERSORT algorithm. Transcription factor interaction and small molecule drug analyses of the Hub genes were also performed. Using the GSE233973 and GSE3365 datasets, 151 differentially expressed genes (DEGs) were identified. GO enrichment analysis revealed involvement in leukocyte migration and chemotaxis, response to lipopolysaccharides, response to biostimulatory stimuli, and regulation of interleukin-8 (IL-8) production. Ten Hub genes (TLR4, IL10, CXCL8, IL1B, TLR2, CXCR2, CCL2, IL6, CCR1 and MMP-9) were identified via the PPI network and Cytoscape software. Enrichment analysis of the Hub genes focused on the lipopolysaccharide response, bacterial molecular response, biostimulatory response and leukocyte movement. Validation using the GSE27411 and GSE179285 datasets revealed that MMP-9 was significantly upregulated in both the H. pylori and IBD groups. The CIBERSORT algorithm revealed immune infiltration differences between the control and disease groups of IBD patients. Additionally, the CMap database identified the top 11 small molecule compounds across 10 cell types, including TPCA-1, AS-703026 and memantine, etc. Our study revealed the co-pathogenic mechanism between H. pylori and IBD and identified 10 Hub genes related to cellular immune regulation and signal transduction. The expression of MMP-9 is significantly upregulated in both H. pylori infection and IBD. This study provides a new perspective for exploring the prevention and treatment of H. pylori infection and IBD.

Gut Microbiota Associated with Clostridioides difficile Carriage in Three Clinical Groups (Inflammatory Bowel Disease, C. difficile Infection and Healthcare Workers) in Hospital Field.

Clostridioides difficile is an anaerobic spore-forming Gram-positive bacterium. C. difficile carriage and 16S rDNA profiling were studied in three clinical groups at three different sampling times: inflammatory bowel disease (IBD) patients, C. difficile infection (CDI) patients and healthcare workers (HCWs). Diversity analysis was realized in the three clinical groups, the positive and negative C. difficile carriage groups and the three analysis periods. Concerning the three clinical groups, β-diversity tests showed significant differences between them, especially between the HCW group and IBD group and between IBD patients and CDI patients. The Simpson index (evenness) showed a significant difference between two clinical groups (HCWs and IBD). Several genera were significantly different in the IBD patient group (Sutterella, Agathobacter) and in the CDI patient group (Enterococcus, Clostridioides). Concerning the positive and negative C. difficile carriage groups, β-diversity tests showed significant differences. Shannon, Simpson and InvSimpson indexes showed significant differences between the two groups. Several genera had significantly different relative prevalences in the negative group (Agathobacter, Sutterella, Anaerostipes, Oscillospira) and the positive group (Enterococcus, Enterobacteriaceae_ge and Enterobacterales_ge). A microbiota footprint was detected in C. difficile-positive carriers. More experiments are needed to test this microbiota footprint to see its impact on C. difficile infection.

Clinical Significance of Erythroferrone and Bone Morphogenetic Protein-6 in Patients with Anemia in the Course of Inflammatory Bowel Disease.

In recent years, a steady increase in the incidence of inflammatory bowel diseases (IBD) has been observed with anemia as their most common extraintestinal symptom. Erythroferrone and Bone Morphogenetic Protein 6 (BMP-6) are recently identified cytokines involved in the process of increased erythropoiesis in anemia of various pathomechanisms. The aim of this study was to analyze the concentration of erythroferrone and BMP-6 in IBD patients in relation to clinical and laboratory data. The study comprised 148 patients: 118 with IBD, including 73 (61.85%) diagnosed with anemia (42 with Crohn's disease (CD) (66.7%) and 31 (56.4%) with ulcerative colitis (UC)) and 30 as a control group. The erythroferrone concentration was significantly higher in IBD patients with anemia (p = 0.009) and higher in UC patients both with and without anemia (p = 0.018), compared to the control group. In CD, no similar difference was observed between patients with and without anemia. Regarding BMP-6, higher levels were found in CD patients with anemia compared to the control group (p = 0.021). The positive correlation between BMP-6 and iron concentration in UC was also noticed. In conclusion, we confirm an increase in erythroferrone concentration in the entire group of IBD patients with anemia, while BMP-6 levels were higher only in anemic CD patients. Due to the clinical importance of anemia in IBD, this problem is worth further analysis and research projects.

Differentiating Childhood Traumas in Inflammatory Bowel Disease.

Inflammatory bowel disease is characterized by chronic inflammation of the gastrointestinal tract. Research on inflammatory bowel disease has shown a connection to childhood traumatic events. However, few studies have focused on specific types of traumatic experiences and the impact of confiding in others on disease-related outcomes. This comparative, cross-sectional study expected that: (1) patients would report higher prevalence rates of childhood traumas than healthy controls; (2) healthy controls would report fewer and less severe traumatic experiences than patients and less confiding in others compared to patients; (3) childhood trauma severity would be indirectly related to depressive symptoms through resilience and confiding in others would moderate this relationship. Participants completed an online survey; an inflammatory bowel disease patient group (N = 195, Mage = 40.48, 76.4% female) was compared to a similarly recruited sample of healthy controls (N = 190, Mage = 31.16, 59.5% female). Patients reported a higher prevalence of experiencing sexual traumas (P = .031), major upheavals (i.e., disruptions) (P = .048), and violence (P = .050) than controls. Patients had significantly higher total trauma severity odds ratios (OR 0.89, 95% CI[0.81,0.97]) and significantly lower total confiding in other odds ratios than controls (OR 1.09, 95% CI[1.02,1.16]). Childhood trauma severity was indirectly related to depressive symptoms through resilience, b = .05, SE = 0.09, 95% CI[0.01,0.09]; however, confiding did not moderate this relationship. Patients reported more sexual, disruptive, and violent traumas. Although confiding did not act as a moderator, trauma was related to depressive symptoms through resilience.

P140 Costs of home-monitoring by telemedicine versus standard care management of Inflammatory Bowel Disease – a Danish register-based five-year follow-up study

Abstract Background The increasing incidence of Inflammatory bowel diseases (IBD) with subsequent increasing use of costly biological treatments such as well as the need for tight control of IBD places a significant economic direct and indirect cost burden on health care systems. Thus, eCare Constant-Care APP, home-monitoring of Patient Reported Outcome (PROs-SCCAI/HB-I, quality of life QoL, Disability index WEB-DI) and calprotectin (POCT-Point of Care Test) was introduced at North Zealand Hospital (NOH) in Denmark in 2015. The aim of this study was to assess long-term cost effectiveness of remote telemedicine services (eCare) compared to standard care (sCare) for IBD patients during 5 years follow-up. Methods A retrospective register-based study was carried out among patients with ulcerative colitis (UC) or Crohn’s disease (CD) continuously included in the telemedicine service Constant Care (CC) in 2015-2020. Direct and indirect healthcare costs over a 5-year period were obtained from Danish registers and compared to a control group of IBD patients from all five regions in Denmark who were 1:5 matched on year of birth, gender, education, income, disease, use of biologics, duration of disease and Charlson Comorbidity index. The IBD patients (cases and controls) were identified in the National Patient Register (NPR) via registered ICD-10 diagnosis codes. Direct and indirect costs were estimated on a yearly basis from two years before inclusion in CC (i.e., the index year) and five years after using a linear regression model. Results A total of 572 IBD patients were included in the study. Average annual costs of IBD-related outpatient visits were significantly (P&amp;lt;.005) higher among patients enrolled in CC compared to controls before and after index date whereas costs of hospital admissions were non-significant (ns). However, a slight decrease was observed in year 2 and 5 from index year (ns). The total direct costs were higher among CC patients compared to controls in the year prior to enrollment in CC and the five years after (Figure 1) primarily driven by the costs of outpatient visits. Significantly (P&amp;lt;.05) fewer CC patients were on early retirement compared to controls and CC patients received less public transfer payments compared to controls (ns). Conclusion Telemedicine care was associated with higher cost than standard care. One potential confounder is inefficient out-patient registration in NRP which highlights the need for continuous validation of clinical registration approaches in Denmark. A prospective RCT is warranted in future.

Evaluation of Tp-e interval and Tp-e/QTc ratio in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD), amultisystemic inflammatory disorder, has been associated with increased risk of cardiovascular problems, including complications such as conduction defects and arrhythmias. Therefore, the early assessment of the risk factors predisposing to ventricular arrhythmias is crucial, since it can improve clinical outcomes. The objective of the present study is to evaluate ventricular repolarization by using Tp‑e interval and Tp-e/QTc ratio as candidate markers of ventricular arrhythmias in patients with IBD. The presented study was designed as asingle-center prospective cohort study. The study population consisted of 175patients with IBD and 175 healthy volunteers. The Tp‑e interval, corrected QT (QTc), and Tp-e/QTc ratio were measured from the 12-lead electrocardiogram. These parameters were compared between groups. The groups were similar in terms of electrocardiographic findings such as heart rate, QRS interval, and QTc interval. However, Tp‑e interval (87.0 ms, interquartile range, IQR 81.0-105.0 ms vs. 84.0 ms, IQR 74.0-92.0 ms; p < 0.001) and Tp-e/QTc ratio (0.21 ± 0.04 vs. 0.19 ± 0.05; p < 0.001) were significantly increased in IBD patient group compared to control group. Notably, apositive correlation was demonstrated between Tp‑e interval, Tp-e/QTc ratio and disease duration (Spearman's Rho = 0.36, p < 0.001 for Tp‑e; Spearman's Rho = 0.28, p < 0.001 for Tp-e/QTc). This study demonstrated that IBD patients are at increased risk of disrupted ventricular repolarization (increased Tpe, Tpe/QTc ratio). In addition, apositive correlation was demonstrated between Tp‑e interval, Tp-e/QTc ratio, and disease duration. Therefore, IBD patients, especially those with long-standing diseases, should be more closely screened for ventricular arrhythmias.

The impact of COVID-19 pandemic on IBD surgery: a single center experience.

The spread of COVID-19 pandemic forced the national healthcare system to reorganize almost all surgical services, in order to maintain an adequate therapeutic offer. At General Surgery department of Fondazione Policlinico Gemelli in Rome, surgical procedures were progressively reduced to provide beds and personnel for COVID-19. The aim of our study was to analyze the effect of one year of COVID-19 pandemic on Inflammatory Bowel Disease (IBD) surgery in a cohort of patients and evaluate post-operative short-term complications. Our team retrospectively analyzed the records of IBD patients who were referred to an IBD-related resective surgery from January 2020 to December 2020. These patients were compared to a comparable group of IBD patients who were operated from January 2019 to December 2019. A total of 160 patients were included in the study. Median age was 44 (range 15-77). Patients were referred for Ulcerative colitis (23.1%) and Crohn's disease (76.9%). Eighty-three patients underwent surgery from January 2020 to December 2020, which constitutes a 4.6% increase in the number of patients compared to the same period in 2019. Median post-operative hospital stay increased (7 days in 2019 vs. 6 days in 2020). Laparoscopic was the most frequently performed procedure during both periods (49% in 2019 and 59% in 2020). Complication rates, reported as Clavien-Dindo score 3 or 4, slightly decreased in 2020 (6.5 in 2019 vs. 4.8 in 2020). PCR test for detection of COVID-19 infection was conducted in all the patients before the hospitalization. Two patients out of 70 were tested positive for COVID-19 and their surgeries were rescheduled. There was no significant reduction in IBD resective surgeries at our center in 2020, nor a deterioration of the outcomes. A reduction of other elective surgical procedures had to be carried out and adequate protective measures for both patients and healthcare workers were established.

Inflammasome-targeting natural compounds in inflammatory bowel disease: Mechanisms and therapeutic potential.

Inflammatory bowel disease (IBD), mainly including Crohn’s disease and ulcerative colitis, seriously affects human health and causes substantial social and economic burden. The pathogenesis of IBD is still not fully elucidated, whereas recent studies have demonstrated that its development is associated with the dysfunction of intestinal immune system. Accumulating evidence have proven that inflammasomes such as NLRP3 and NLRP6 play a prominent role in the pathogenesis of IBD. Thus, regulating the activation of inflammasomes have been considered to be a promising strategy in IBD treatment. A number of recent studies have provided evidence that blocking inflammasome related cytokine IL-1β can benefit a group of IBD patients with overactivation of NLRP3 inflammasome. However, therapies for targeting inflammasomes with high efficacy and safety are rare. Traditional medical practice provides numerous medical compounds that may have a role in treatment of various human diseases including IBD. Recent studies demonstrated that numerous medicinal herb derived compounds can efficiently prevent colon inflammation in animal models by targeting inflammasomes. Herein, we summarize the main findings of these studies focusing on the effects of traditional medicine derived compounds on colitis treatment and the underlying mechanisms in regulating the inflammasomes. On this basis, we provide a perspective for future studies regarding strategies to improve the efficacy, specificity and safety of available herbal compounds, and to discover new compounds using the emerging new technologies, which will improve our understanding about the roles and mechanisms of herbal compounds in the regulation of inflammasomes and treatment of IBD.

Therapeutic drug monitoring in inflammatory bowel disease: At the right time in the right place.

Therapeutic drug monitoring (TDM) was one of most sought-after objective tools to determine therapeutic efficiency of different biologics and its role in the management of patients with inflammatory bowel disease (IBD) was regarded with great anticipation. But implementation of the TDM in clinical practice was challenged by several factors including uncertainty of the optimal cut-off values, assay variable sensitivity in detecting drug levels and antibodies and, most importantly, individual pharmacokinetics. While reactive TDM was embraced in clinical practice as a useful tool in assessing lack of response to therapy, the utility of proactive TDM in managing IBD therapy is still challenged by the lack of consistency between evidence. Described here, there are four groups of IBD patients for whom proactive TDM has the potential to greatly impact their therapeutic outcomes: Patients with perianal Crohn’s disease, patients with severe ulcerative colitis, pregnant women with IBD and children. As the future of IBD management moves towards personalizing treatment, TDM will be an important decision node in a machine learning based algorithm predicting the best strategy to maximize treatment results while minimizing the loss of response to therapy.

Echocardiographic assessment of the left ventricular systolic function in patients with inflammatory bowel disease

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Research data have shown evidence of association between inflammatory bowel disease (IBD) and cardiovascular disease (CVD). Early detection of CVD in IBD patients is crucial for their further management. Purpose In this case–control study, we assessed the left ventricular (LV) systolic function of IBD patients with no evidence of CVD and compared it with healthy volunteers. Methods The study population consisted of consecutive IBD patients with no evidence of CVD or relative medical history who were referred to our laboratory from January 2021 to July 2021 and a group of healthy volunteers. Standard 2-dimensional transthoracic echocardiography was performed in each group and LV systolic function was assessed by LV ejection fraction (LVEF) with modified Simpson’s rule and LV global longitudinal strain (LVGLS). As the normal distribution assumption was not met, the Mann Whitney U test (new procedure) was used to compare the variables within the two groups, while correlations between the 2 continuous variables were examined with the Spearman"s correlation analysis. A p value of &amp;lt;0.05 was considered statistically significant. Results Twenty-four IBD patients (15 men, 9 women, 12 with Crohn’s disease, 12 with ulcerative colitis) of a mean age of 39.63 years [minimum = 23, maximum = 56, standard deviation (SD)=9.56] were enrolled in the study. The control group consisted of 24 healthy volunteers (15 men, 9 women) of a mean age of 37.75 years (minimum = 17, maximum = 58, SD = 12.12). For the IBD group, the mean LVEF was 57.71% and the median was 58% (minimum = 52%, maximum = 63%, SD = 3.56%), while the mean LVGLS was -18.23% and the median was -18.65% (minimum absolute value = 12.40%, maximum absolute value = 22.70%, SD = 2.48%). For the control group, the mean LVEF was 61.21% and the median was 60% (minimum = 55%, maximum = 68%, SD = 3.43%), while the mean LVGLS was -20.08% and the median was -20% (minimum absolute value = 17%, maximum absolute value = 25.2%, SD = 1.96%). The IBD patient group showed significantly lower LVEF measurements (mean rank = 18.98, Mann-Whitney U = 155.500, p = 0.006) and absolute LVGLS values (mean rank = 19.40, Mann-Whitney U = 165.500, p = 0.011) compared to the control group (LVEF mean rank = 30.02, LVGLS absolute value mean rank = 29.60). Correlation analysis revealed that LVEF was positively correlated with LVGLS absolute values in both groups (IBD patients: Spearman"s rs = 0.532, p = 0.008, control group: Spearman"s rs = 0.565, p = 0.004). Conclusion Subclinical LV systolic impairment seems to be evident in IBD patients and echocardiographic assessment may facilitate its early detection. Abstract Figure.

The association of the quality of sleep with proinflammatory cytokine profile in inflammatory bowel disease patients

BackgroundThe role of circadian rhythm abnormalities in patients with inflammatory bowel disease (IBD) remains relatively unknown. The aim of this study was to identify the inflammatory cytokine profile in the IBD patients and its relationship with the quality of sleep.MethodsProspective, single-center observational cohort study was performed. In all enrolled adult IBD patients, the disease activity was assessed using Crohn’s Disease Activity Index (CDAI) for Crohn’s disease (CD) and Partial Mayo Score for ulcerative colitis (UC), respectively. To assess the quality of sleep, all patients were asked to respond to a questionnaire to define Pittsburgh Quality Sleep Index (PSQI). From all enrolled patients, 15 ml venous blood was taken to determine serum inflammatory cytokine levels and perform standard laboratory tests.ResultsFifty-two IBD patients were enrolled in the study: 32 with CD and 20 with UC. The poor sleep was noted in 69.4% of patients with clinically active and in 6.3% of patients with inactive disease. In the group of IBD patients with poor sleep, the significantly higher level of serum IL-6, IL-17, and IL-23 were observed. In IBD patients with exacerbation, the significantly higher level of serum IL-6, IL-17, and IL-23 were recorded.ConclusionsThe relationship between quality of sleep and proinflammatory cytokine profile may show us a predisposition for the development of inflammatory intestinal lesions in IBD patients with sleep disturbances. This knowledge may allow the pharmacological and behavioral therapies of circadian rhythm abnormalities to become new significant targets in IBD patients.

P331 The safety of tioguanine exposure during pregnancy: a case series of seventy-three pregnancies

Abstract Background Azathioprine and mercaptopurine exposure during conception and pregnancy has been considered safe in patients with inflammatory bowel disease (IBD). Its use is not associated with a higher risk of preterm birth or low birthweight. Data on the safety of tioguanine, an alternative thiopurine-derivate, in pregnant IBD patients is limited. In a small case series, tioguanine appeared safe for both mother and fetus. In this study, we describe the teratogenicity and safety of tioguanine during pregnancy in a large group of IBD patients. Methods We performed a preliminary analysis of our ongoing multicenter descriptive case series of female IBD patients who were treated with tioguanine at some point during their pregnancy. Data regarding disease and medication history, pregnancy course and neonatal outcomes, such as preterm birth, miscarriage, birthweight, Apgar scores and congenital abnormalities were collected by the treating physician. Results Seventy-three pregnancies, including three twin pregnancies were collected. Most women (80%) had Crohn’s disease and the mean age during delivery was 31 years (range 21-42). Tioguanine was used throughout the entire pregnancy in 89% with a median daily dose of 20 mg. Five (6.8%) of these pregnancies resulted in a miscarriage, all within the first 13 weeks. No congenital abnormalities were reported in all seventy-one live born children. In the singleton pregnancies the median birthweight was 3375 gram (IQR 3075-3739, N=61, 4 missing values) with a median gestational age of 39.0 weeks (IQR 38.3-40.0, N=61). Four children (6.5%) were born prematurely (&amp;lt;37 weeks). Two of them were born after a spontaneous onset of labor with respectively 33 + 6 and 35 + 6 weeks, while in the other two labor was induced due to a placental abruption (32 + 1 weeks) or HELLP syndrome (31 + 4 weeks). Three children (4.9%) had a low birthweight (&amp;lt;2500 gram), all of them born prematurely, and five patients (8.3%, N=60, 5 missing values) were born small for gestational age (&amp;lt;10th percentile). The median Apgar score after 1 and 5 minutes was respectively 9 (IQR 8-9, N=58) and 10 (IQR 9-10, N=59). Two neonates (3.4%), one born pre-and dysmature and the other a premature second-born twin, had an Apgar score (&amp;lt;7) after 5 minutes. Conclusion In this large case-series, tioguanine exposure during pregnancy was not associated with an increased risk of congenital abnormalities, low birthweight or preterm birth in IBD patients. These data support the safe use of tioguanine during pregnancy in IBD.