Introduction Inflammatory Bowel Disease Research Articles

The effects of underlying inflammatory bowel disease on the outcomes of primary sclerosing cholangitis liver transplant recipients

IntroductionInflammatory bowel disease (IBD) influences primary sclerosing cholangitis (PSC) severity, however, the impact of IBD on PSC liver transplantation (LT) outcomes is poorly understood. We aimed to elucidate the impact of IBD in modulating PSC LT outcomes. MethodsUsing UNOS data from 2010 through 2021, we identified PSC LT candidates with and without (±) IBD. We used adjusted competing-risk regression analysis to evaluate waitlist outcomes, Kaplan-Meier analysis to assess graft survival, and Cox proportional hazards modeling to identify factors associated with graft survival. ResultsOut of 5,586 PSC candidates added to the waitlist, 3,652 patients had IBD. Older age (SHR 1.01; 95 %CI 1.01–1.02) and initial MELD/PELD (SHR 1.03; 95 %CI 1.02–1.04) were associated with increased risk of waitlist mortality, while private insurance (SHR 0.00; 95 %CI 0.00–0.01) with reduced risk. PSC-IBD LT recipients had increased prevalence of cholangiocarcinoma (4.8 % vs 3.4 %, p=0.005). Longer donor cold ischemia times (HR 1.06; 95 %CI 1.03–1.09), presence of recipient diabetes (HR 1.52; 95 %CI 1.13–2.05), and employment (HR 0.75, 95 %CI 0.60–0.94) had an increased risk of graft failure among PSC patients with IBD, not seen in those without IBD. ConclusionRegardless of IBD, LT for PSC results in excellent outcomes. Certain clinicodemographic factors impacted waitlist and recipient mortality highlighting potential targets to enhance outcomes.

Assessment of the length of sick leave in patients with inflammatory bowel disease

IntroductionInflammatory bowel disease (IBD) is a chronic disorder that can lead to periods of work-related temporary disability (TD), which may result in the need for permanent disability. The objective was to assess the impact of IBD on patients' temporary disability by analyzing periods, duration, and causes. It also investigates risk factors influencing the severity, frequency, and duration of flare-ups and associated complications in IBD patients. MethodThe study includes patients aged 18–65, with at least 1 day of TD in 2019 (Pre-COVID), referred or not by UMEVI, due to reasons related to IBD. ResultsA total of 172 patients were included, and in all cases, TD was associated with IBD. TD was higher in patients over 30 years old, with anxious depressive disorder, who required hospitalization and did not receive prednisone treatment (p < 0.05). TD duration was longer in patients belonging to the Special Regime for Self-Employed Workers (RETA): 67 days (IQR: 22–160) versus the General Regime (RG): 33 days (IQR: 8–110), with no statistically significant difference (p = 0.120). The mean cost (€) per worker in this series was €745.5 (IQR: 231–2608.2). ConclusionsIBD has a significant impact on patients' temporary work disability. The duration of TD was longer in patients older than 30 years, with anxious-depressive disorder, who required hospital admission and did not receive steroid treatment.

FP2.5 - Predictors for anastomotic leak (AL) in inflammatory bowel disease (IBD) patients and its associated postoperative (PO) complications; A cohort of a single institution experience

Abstract Introduction IBD patients are highly susceptible to PO morbidities. This study aimed to look at the predictors of AL and the associated morbidities during hospital stays to increase the awareness of these patients. Methods A 5-year retrospective study in DGH. All variables were evaluated:patient-dependent (Age, Gender, BMI, ethnic group, comorbidities),disease-dependent (type of IBD, disease location, disease duration), surgery-dependent (duration, CEPOD type, approach, type of resection),Postoperative(CRP level, VTE, ITU admission, LOS, complications).All data were analysed using SPSS22, and Chi-square test. Results 131 patients were admitted for IBD resection. Median age 37 years. 76 (58%) were female, Chron’s disease was 98 (74.8%). 101 (77.1%) were done laparoscopically, 87 (66.4%)were elective, and the median LOS was 7days.63 (48.1%) has bowel anastomosis and 15 (23.8%) have AL. The median CRP on PO day3 for AL patients was 118. There was no significant association between PO day3CRP and IBD type with AL (P=0.4, 0.7); however, DVT and PE were associated with AL (P=0.001 and 0.039). Patients with AL had a high tendency for ITU admission with longer LOS (P=0.000).Long stays were seen in patients with leaks post-emergency than elective resections (P=0.047, 0.112). AL was associated with chest infection (P=0.001), collection (P=0.006),wound infection (p=0.000), and a higher rate of re-operation within 30 days (p=0.019). Conclusion PO day3CRP is not an independent predictor for AL. Our cohort of IBD patients who had bowel anastomosis showed a significant correlation between VTE and AL.AL was associated with chest and wound infections, high chance of a long ITU stay and subsequently, a long hospital stay. IBD patients with AL are vulnerable to VTE so need high care on these regards.

Study of Inflammatory Bowel Disease in Patients Undergoing Colonoscopy at a Tertiary Center of Nepal.

Introduction Inflammatory bowel disease (IBD) is a chronic inflammatory condition of thegastrointestinal tract that includes ulcerative colitis (UC) and Crohn's disease (CD). The incidence and prevalence ofdisease are on a rising trend. Increasedcase detection is related tobetterhealth awareness andimprovedavailability of diagnostic services in the community. This articleaims to calculate the incidence of IBD per 1,000 colonoscopies per yearandto study the clinical and demographic characteristics of patients with IBD. Methodology It was a prospective observational study done at the National Academy of Medical Sciences, Bir Hospital, Kathmandu, Nepal, from March 2023 to February 2024.All the patients who underwent colonoscopy during the study period were assessed for possible diagnosis of IBD. TheIncidence rate was calculated as new IBD cases per 1,000 colonoscopies per year. Demographic and clinical profiles of the patients were collected. Results Among 1,248 patients who underwent colonoscopy during the study period, IBD was detected in 52 patients (4.16%). UC was diagnosed in 43 patients and the incidence rate of it was calculated to be 34.4 casesper 1,000 colonoscopies per year. Similarly, CD was diagnosed in nine patients with its incidence rate being 7.2 cases per 1,000 colonoscopies per year. Disease was predominantly seen in females (F:M ratio - 1.36:1). The mean age at diagnosis of IBD was 39.67 ± 14.53 years, with patients with CD being slightly younger than those with UC. The majority of patients with UC had pancolitis. The median time todiagnosis from symptom onset was three years (range: 6 months to 7 years) for CD and 10 months for patients with UC (range: 2 months to 5 years). The most common extra-intestinal manifestations were arthralgia (11, 21.15%) and arthritis (7, 13.46%). Traditional drugs like mesalamine, prednisolone, and azathioprine were commonly prescribed. Biologics were used only in two (3.84%) patients, including infliximab and adalimumab. Janus kinase inhibitor (tofacitinib) was used in three(5.76%) patients in cases of acute severe UC. Conclusions Due to the rising trend of awareness in health and availability of colonoscopyservices in our country like Nepal, the incidence of IBD is seen to be quite high. UC was seen more commonly than CD, and females were predominantly involved. The majority of patients belonged to the young and middle-aged population.The majority of patients with UC had extensive colitis, while patients with CD had ileo-colonic disease with non-stricturing, non-penetrating phenotypes. Arthralgia and arthritis were the most common extra-intestinal manifestations. Conventional drugs like mesalamine, prednisolone, and immunomodulators such as azathioprine were mostly used. The use of biologics was fairly low. This study certainly contributes to the existing literature from Nepal regarding IBD.

Co-delivery of a curcumin and asafoetida as a bioavailable complex using fenugreek galactomannan hydrogel scaffold alleviates inflammatory bowel disease on experimental animals

IntroductionInflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder characterised by the disruption of the epithelial barrier and formation of mucosal ulceration. Though the current treatment mainly includes synthetic drugs, herein, we hypothesised that a co-delivery of bioavailable and water-soluble forms of turmeric extract (curcumin) along with asafoetida oleo-gum-resin (hereinafter referred to as ‘CUAS’) may have synergistic effects to alleviate IBD safely. MethodsThe study was conducted in two phases. In the first phase, bioavailability of the formulation was investigated and in the second phase, its effect on 2,4,6- trinitrobenzene sulfonic acid (TNBS)-induced IBD model of rats were investigated. In this model, Wistar rats (n = 30) were randomised into 5 groups, [Group I-control, Group II–TNBS treated IBD group (100 mg/kg; intrarectal), Group III-Standard drug (Sulfasalazine; 50 mg/kg b. wt. orally), Group IV – standard curcumin complex (UC; 200 mg/kg b. wt.), Group V –Curcumin/asafoetida co-delivery form (CUAS; 200 mg/kg b. wt.)]. IBD was induced to group II to V animals, and then treated with the respective drugs for 24 days. Then the animals were sacrificed and various biochemical parameters including ulcer index, antioxidant levels, oxidative stress markers, and histopathological analysis of the colon were carried out. ResultsThe results revealed a significant reduction (P < 0.05) of the clinical manifestations related to IBD, along with a significant reduction (P < 0.05) for the ulcer index, oxidative stress, and significant enhancement (P < 0.05) in endogenous antioxidant enzyme levels among CUAS treated animals. Histopathological observations also showed a significant reduction in TNBS-induced colon lesions. No necrosis, cellular infiltration, haemorrhage, or oedema was observed among the CUAS-treated animals, indicating better gastroprotective effect of CUAS compared to the standard curcumin treatment. ConclusionsThe enhanced effect of CUAS was attributed to the improved bioavailability (22.8-fold) of CUAS compared to standard curcumin treated group.

Aloe-emodin alleviates inflammatory bowel disease in mice by modulating intestinal microbiome homeostasis via the IL-4/IL-13 axis

IntroductionInflammatory bowel disease (IBD) is a global health concern. Aloe-emodin (AE) has diverse pharmacological benefits, including anti-inflammatory effects. However, its role in IBD remains unclear, prompting our investigation of its regulatory effects and mechanisms in an IBD mouse model. MethodsWe studied the therapeutic efficacy of AE in alleviating symptoms and modulating cytokine secretion in a murine model of dextran sulfate sodium (DSS)-induced colitis. BALB/c mice were administered DSS to induce colitis and were subsequently treated with varying doses of AE. Changes in body weight, fecal lipocalin-2 (LCN2) levels, colon tissue histology, and serum cytokine concentrations were evaluated to assess the effects of AE treatment. Additionally, 16 S rRNA sequencing was used to analyze alterations in the composition of the gut microbiota following AE intervention. Finally, the database was used to analyze the signaling pathways associated with IBD in AE and to detect the expression levels of interleukin (IL)-4 pathway using real-time quantitative reverse transcription PCR. Exogenous IL-4 was used in rescue experiments to observe its effects on the disease process of IBD under AE regulation. ResultsAE treatment resulted in a dose-dependent mitigation of weight loss, reduction in fecal LCN2 levels, and amelioration of histological damage in DSS-induced colitis in mice. The levels of superoxide dismutase and catalase increased, whereas malondialdehyde decreased following AE treatment, indicating a dose-dependent alleviation of colitis symptoms. Furthermore, AE administration attenuated the secretion of pro-inflammatory cytokines, including IL-17, tumor necrosis factor-alpha (TNF-α), and chemokine ligand 1, while promoting the expression of anti-inflammatory cytokines IL-4 and IL-13. Analysis of the gut microbiota revealed that AE effectively suppressed the overgrowth of colitis-associated bacterial species and restored microbial homeostasis. Finally, we found that overexpression of IL-4 was able to reverse the therapeutic effect of AE for DSS-induced IBD. ConclusionAE shows promise in alleviating colitis severity, influencing inflammatory cytokines, and modulating the gut microbiota in an IBD mouse model via the IL-4/IL-13 pathway, suggesting its potential as a natural IBD remedy.

Efficacy and safety of infliximab and adalimumab in inflammatory bowel disease patients

IntroductionInflammatory bowel disease (IBD), consists of two primary types: Ulcerative Colitis (UC) and Crohn’s Disease (CD). Infliximab (IFX) and Adalimumab (ADA) are frequently utilized in the management of moderate to severe cases of IBD.AimThis study aimed to assess the efficacy and safety of IFX and ADA in individuals diagnosed with moderate to severe IBD.MethodThis study is a prospective open-labeled randomized parallel study that included moderate to severe IBD patients treated with either IFX or ADA. A total of 56 patients participated, with 34 patients received IFX and 22 patients received ADA. Various measures, including Crohn’s Disease Activity Index (CDAI), Mayo Score/ Disease Activity Index (DAI), and C-reactive protein (CRP) levels, were taken at baseline and week 14 to assess the efficacy of the treatments. In addition, the levels of drugs and sTREM-1 were measured at 14 weeks. Patient safety was monitored throughout the study period.ResultsIn the group received IFX, there was a notable decrease in CDAI (P = 0.045), DAI (P = 0.026), and CRP (P = 0.023 for CD, and P = 0.021 for UC) levels. In addition, the group received ADA experienced a significant reduction in CDAI (P = 0.001), DAI (P = 0.032), and CRP (P < 0.018 for CD and P = 0.003 for UC) levels. Responders had higher drug concentrations than non-responders, notably IFX concentration was higher in responders with CD (P = 0.001) and UC (P < 0.001). ADA concentration was higher in UC (P <= 0.001) and all CD patients responded to the treatment. The same trend was observed for sTREM-1 levels in CD and UC patients (P = 0.042, and P = 0.015, respectively) in the IFX group. In UC patients treated with ADA, the level of sTREM-1 was significantly low (P = 0.002).ConclusionBoth IFX and ADA have a good safety profile and deliver a beneficial clinical and laboratory response in moderate-severe IBD patients.Clinical Trial RegistrationThis study is registered on ClinicalTrials.gov under the identifier NCT05291039. (You can access the study at https://clinicaltrials.gov/study/NCT05291039 (First Posted: March 22, 2022).

Umbrella review of risk factors for inflammatory bowel disease: a study protocol

IntroductionInflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder that arises from complex interactions between genetics, environment and gut microbiota. It encompasses Crohn’s disease, ulcerative colitis and IBD-unclassified. The...

Novel biomarker profiles to improve individual diagnosis and prognosis in patients with suspected inflammatory bowel disease: protocol for the Nordic inception cohort study (NORDTREAT)

IntroductionInflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective...

Sedanolide alleviates DSS-induced colitis by modulating the intestinal FXR-SMPD3 pathway in mice

IntroductionInflammatory bowel disease (IBD) is a global disease with limited therapy. It is reported that sedanolide exerts anti-oxidative and anti-inflammatory effects as a natural phthalide, but its effects on IBD remain unclear. ObjectivesIn this study, we investigated the impacts of sedanolide on dextran sodium sulfate (DSS)-induced colitis in mice. MethodsThe mice were administered sedanolide or vehicle followed by DSS administration, after which colitis symptoms, inflammation levels, and intestinal barrier function were evaluated. Transcriptome analysis, 16S rRNA sequencing, and targeted metabolomics analysis of bile acids and lipids were performed. ResultsSedanolide protected mice from DSS-induced colitis, suppressed the inflammation, restored the weakened epithelial barrier, and modified the gut microbiota by decreasing bile salt hydrolase (BSH)-expressing bacteria. The downregulation of BSH activity by sedanolide increased the ratio of conjugated/unconjugated bile acids (BAs), thereby inhibiting the intestinal farnesoid X receptor (FXR) pathway. The roles of the FXR pathway and gut microbiota were verified using an intestinal FXR-specific agonist (fexaramine) and germ-free mice, respectively. Furthermore, we identified the key effector ceramide, which is regulated by sphingomyelin phosphodiesterase 3 (SMPD3). The protective effects of ceramide (d18:1/16:0) against inflammation and the gut barrier were demonstrated in vitro using the human cell line Caco-2. ConclusionSedanolide could reshape the intestinal flora and influence BA composition, thus inhibiting the FXR-SMPD3 pathway to stimulate the synthesis of ceramide, which ultimately alleviated DSS-induced colitis in mice. Overall, our research revealed the protective effects of sedanolide against DSS-induced colitis in mice, which indicated that sedanolide may be a clinical treatment for colitis. Additionally, the key lipid ceramide (d18:1/16:0) was shown to mediate the protective effects of sedanolide, providing new insight into the associations between colitis and lipid metabolites.

Ischemic heart disease mortality in individuals with inflammatory bowel disease: A nationwide analysis of disparities in the United States

IntroductionInflammatory bowel disease (IBD) is linked to immune-mediated pathogenesis and a pro-inflammatory state, leading to accelerated atherosclerosis. This earlier onset of clinical cardiovascular disease poses significant morbidity and mortality. We sought to identify IHD mortality trends in individuals with IBD in the United States (US). MethodsMortality due to ischemic heart diseases (IHD) as the underlying cause of death with the IBD as a contributor of death were queried from death certificates using the CDC database from 1999 to 2020. Yearly crude mortality rates (CMR) were estimated by dividing the death count by the respective population size, reported per 100,000 persons. Mortality rates were adjusted for age using the Direct method and compared by demographic subpopulations. Log-linear regression models were utilized to assess temporal variation (annual percentage change [APC]) in mortality. ResultsAge-adjusted mortality rates (AAMR) decreased from 0.11 in 1999 to 0.07 in 2020, primarily between 1999 and 2018 (APC -4.41, p < 0.001). AAMR was higher among male (AAMR 0.08) and White (AAMR 0.08) populations compared to female populations (AAMR 0.06) and Black (AAMR 0.04) populations, respectively. No significant differences were seen when comparing mortality between urban (AAMR 0.07) and rural (AAMR 0.08) regions. Southern US regions (AAMR 0.06) had the lowest mortality rates when compared to the other US census regions: Northeastern (AAMR 0.08), Midwestern (AAMR 0.08), and Western (AAMR 0.08). ConclusionDisparities in IHD mortality exist among individuals with IBD in the US based on demographic factors, with an overall decline in mortality during the 22-year period. Further investigation is warranted to confirm these findings and evaluate for contributors to the observed disparities.

Cirugía de la enfermedad inflamatoria intestinal en España: ¿cómo lo estamos haciendo? Resultados iniciales de un registro prospectivo nacional (Registro REIC)

IntroductionInflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), requires a multidisciplinary approach, and surgery is commonly needed. The aim of this study was to evaluate the types of surgery performed in these patients in a nationwide study by hospital type, global postoperative complications, and quality of life after surgery. MethodsA prospective, multicenter, national observational study was designed to collect the results of surgical treatment of IBD in Spain. Demographic characteristics, medical-surgical treatments, postoperative complications and quality of life were recorded with a one-year follow-up. Data were validated and entered by a surgeon from each institution. ResultsA total of 1134 patients (77 centers) were included: 888 CD, 229 UC, and 17 indeterminate colitis. 1169 surgeries were recorded: 882 abdominal and 287 perianal. Before surgery, 81.6% of the patients were evaluated by a multidisciplinary committee, and the mean preoperative waiting time for elective surgery was 2.09±2 meses (P>.05). Overall morbidity after one year of follow-up was 16%, and the major complication rate was 36.4%. Significant differences were observed among centers in complex CD surgeries. Overall quality of life improved after surgery. ConclusionsThere is heterogeneity in the surgical treatment of IBD among Spanish centers. Differences were observed in patients with highly complex surgeries. Overall quality of life improved with surgical treatment.

Association between inflammatory bowel disease and Parkinson's disease: a prospective cohort study of 468,556 UK biobank participants.

Inflammatory Bowel Disease (IBD) and Parkinson's disease (PD) are both chronic, progressive disorders. As such, given the inconclusive results of extensive research on the association between IBD and PD, our study intends to examine this relationship further using the UK Biobank database. We conducted a prospective cohort study using the Cox proportional hazards model, analyzing data from the UK Biobank to investigate the relationship between IBD and PD, following subjects until PD diagnosis, loss to follow up, death or study termination on 30 June, 2023. The results show that IBD had no effect on the risk of PD (HR: 1.356, 95% CI: 0.941-1.955, p = 0.103), and the effect remained consistent in specific Crohn's disease, ulcerative colitis or unclassified IBD populations. In addition, after sensitivity analysis using propensity matching scores and excluding patients diagnosed with PD 5 or 10 years after baseline, IBD had no effect on the risk of PD. However, in the subgroup analysis, we found that in females (HR: 1.989, 95% CI: 1.032-3.835, p = 0.040), the polygenic risk score was highest (HR: 2.476, 95% CI: 1.401-4.374, p = 0.002), and having ulcerative colitis without hypertension (HR: 2.042, 95% CI: 1.128-3.697, p = 0.018) was associated with an increased risk of PD. In conclusion, over an average follow-up period of 13.93 years, we found no significant association between IBD and PD.

Surgery for inflammatory bowel disease in Spain: How are we doing? Initial results of a nationwide prospective registry

IntroductionInflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), requires a multidisciplinary approach, and surgery is commonly needed. The aim of this study was to evaluate the types of surgery performed in these patients in a nationwide study by hospital type, global postoperative complications, and quality of life after surgery. MethodsA prospective, multicenter, national observational study was designed to collect the results of surgical treatment of IBD in Spain. Demographic characteristics, medical-surgical treatments, postoperative complications and quality of life were recorded with a one-year follow-up. Data were validated and entered by a surgeon from each institution. ResultsA total of 1134 patients (77 centers) were included: 888 CD, 229 UC, and 17 indeterminate colitis. 1169 surgeries were recorded: 882 abdominal and 287 perianal. Before surgery, 81.6% of the patients were evaluated by a multidisciplinary committee, and the mean preoperative waiting time for elective surgery was 2.09 ± 2 meses (P > .05). Overall morbidity after one year of follow-up was 16%, and the major complication rate was 36.4%. Significant differences were observed among centers in complex CD surgeries. Overall quality of life improved after surgery. ConclusionsThere is heterogeneity in the surgical treatment of IBD among Spanish centers. Differences were observed in patients with highly complex surgeries. Overall quality of life improved with surgical treatment.

Oligoelements in serum and intestinal tissue of pediatric IBD patients

IntroductionInflammatory bowel disease (IBD) develops through complex interplay of genetic, microbial, immune, and environmental factors. Trace elements alterations are commonly present in IBD and may have influence on IBD development. Heavy metal pollution is one of the major environmental issues nowadays and IBD incidence is rising in countries where industry starts to develop. Metals are implicated in processes that are connected to IBD pathogenesis. AimThe aim of this study was to investigate toxic and trace element levels in pediatric population of IBD patients both in serum and intestinal mucosa. Materials and methodsThis prospective study enrolled children newly diagnosed with IBD in University children’s hospital in Belgrade. Concentrations of thirteen elements: Al, As, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Se and Zn in serum and intestinal mucosa of 17 newly diagnosed children with IBD (10 Crohn’s disease (CD) and 7ulcerative colitis (UC)) and 10 controls were assessed using inductively coupled plasma mass spectrometry (ICP-MS). Intestinal mucosa samples were taken from terminal ileum and six different colon segments (cecum, ascending colon, colon transversum, descending and sigmoid colon and rectum). ResultsThe results demonstrated significant alterations in serum and intestinal mucosa concentrations of investigated elements. Serum iron was significantly decreased in IBD and CD group, compared to controls while serum Cu significantly differed between three investigated groups with highest concentration observed in CD children. Serum manganese was the highest in the UC subgroup. Terminal ileums of IBD patients contained significantly lower amount of Cu, Mg, Mn and Zn with Mn being significantly decreased also in CD patients compared to control. IBD patients’ caecum contained significantly less Mg and Cu while colon transversum tissue samples from IBD and Crohn’s patients contained significantly more chromium than controls. Moreover, sigmoid colon of IBD patients were poorer in Mg than controls (p < 0.05). Colon Al, As and Cd were significantly reduced in IBD, and UC children compared to control. Correlations of investigated elements in CD and UC groups were different from controls. Biochemical and clinical parameters showed correlation with element concentrations in intestines. ConclusionSera of CD, UC and control children significantly differ in Fe, Cu and Mn levels. Serum manganese was the highest in the UC subgroup creating the most prominent and only significant difference between UC and CD subgroups. Terminal ileum of IBD patients contained significantly lower amount of majority of investigated essential trace elements and toxic elements were significantly reduced in colon of IBD and UC patients. Investigation of macro- and microelement alterations in children and adults has potential to further elucidate IBD pathogenesis.

Inflammatory bowel disease is causally related to irritable bowel syndrome: a bidirectional two-sample Mendelian randomization study.

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are lifelong digestive diseases that severely impact patients' quality of life. The existence of a causal association between IBS and IBD remains unclear. This study aimed to determine the direction of causality between IBD and IBS by quantifying their genome-wide genetic associations and performing bidirectional two-sample Mendelian randomization (MR) analyses. Genome-wide association studies (GWAS) among a predominantly European patient cohort identified independent genetic variants associated with IBS and IBD. Two separate databases (a large GWAS meta-analysis and the FinnGen cohort) for both IBS and IBD were consulted to retrieve statistics on instrument-outcome associations. MR analyses included inverse-variance-weighted, weighted-median, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods, and sensitivity analyses were performed. The MR analyses were carried out for each outcome data, followed by a fixed-effect meta-analysis. Genetically predicted IBD was associated with an increased risk of IBS. Odds ratios (95% confidence intervals) for samples of 211,551 (17,302 individuals with IBD), 192,789 (7,476 Crohn's disease cases), and 201,143 (10,293 ulcerative colitis cases) individuals were 1.20 (1.00, 1.04), 1.02 (1.01, 1.03), and 1.01 (0.99, 1.03), respectively. After outlier correction using MR-PRESSO, the odds ratio for ulcerative colitis was 1.03 (1.02, 1.05) (p = 0.001). However, an association between genetically influenced IBS and IBD was not identified. This study confirms that IBD is causally related to IBS, which may interfere with the diagnosis and treatment of both diseases.

Personalizing therapy selection in inflammatory bowel disease

ABSTRACT Introduction Inflammatory bowel disease (IBD) is a complex disease, caused by aberrant immune responses to environmental stimuli where genetic, metabolomic, and environmental variables interact to cause mucosal inflammation. This review sheds light on the different drug and patient related factors that affect personalization of biologics in IBD treatment. Areas covered We utilized the online research database PubMed to carry out literature search pertaining to therapies in IBD. We incorporated a combination of primary literature as well as review articles and meta-analyses in writing this clinical review. In this paper, we discuss the mechanisms of action for different biologics, the genotype and phenotype of patients, and pharmacokinetics/pharmacodynamics of drugs, as factors that influence response rates. We also touch upon the role of artificial intelligence in treatment personalization. Expert opinion The future of IBD therapeutics is one of precision medicine, based on the identification of aberrant signaling pathways unique to individual patients as well as exploring the exposome, diet, viruses, and epithelial cell dysfunction as part of disease pathogenesis. We need global cooperation for pragmatic study designs as well as equitable access to machine learning/artificial intelligence technology to reach the unfulfilled potential of IBD care.

The oft-overlooked cardiovascular complications of inflammatory bowel disease

ABSTRACT Introduction Inflammatory bowel disease (IBD) may be associated with several extraintestinal comorbidities, including cardiovascular disease (CVD). Chronic inflammation is recognized as an important factor in atherogenesis, thrombosis, and myocarditis. Areas covered IBD patients may be at increased risk for developing early atherosclerosis, cardiovascular events, peripheral artery disease, venous thromboembolism, myocarditis, and arrhythmias. Anti-tumor necrosis factor agents and thiopurines have been shown to have a protective effect against acute arterial events, but more research is needed. However, an increased risk of venous thromboembolism and major cardiovascular events has been described with the use of Janus kinase inhibitors. Expert opinion CVD risk is slightly increased in patients with IBD, especially during flares. Thromboprophylaxis is strongly recommended in hospitalized patients with active disease as the benefit of anticoagulation outweighs the risk of bleeding. The pathogenetic relationship between CVD and IBD and the impact of IBD drugs on CVD outcomes are not fully elucidated. CVD risk doesn’t have the strength to drive a specific IBD treatment. However, proper CVD risk profiling should always be done and the best strategy to manage CVD risk in IBD patients is to combine appropriate thromboprophylaxis with early and durable remission of the underlying IBD.

Stigmatization and resilience in inflammatory bowel disease patients at one-year follow-up

IntroductionInflammatory bowel disease (IBD), namely ulcerative colitis and Crohn’s disease, is a chronic relapsing immune-mediated condition that may cause an impairment of social functions due to stigmatisation. Resilience instead is associated with an improvement in coping with adversities and thus may counteract the detrimental effects of stigmatisation. We herein sought to determine the fluctuation of stigmatisation and resilience in a cohort of patients with IBD at 1-year follow-up.MethodsThis is a prospective, monocentric study conducted in a tertiary referral centre. All patients with IBD were assessed at enrolment and at oneyear follow-up. Several clinical and demographic variables were collected. Stigmatisation was assessed through a validated Italian version of the Perceived Stigma Scale for IBD (PSS-IBD), while resilience was assessed through the 25-item Connor Davidson Resilience Scale (CD-RISC25). Also, self-efficacy (SEF) and self-esteem (SES) scales were assessed.ResultsIn this study, 105 patients were included (46 Crohn’s disease, 59 ulcerative colitis; overall mean age 47 years ±11, M:F ratio 1:1.2). None of the 4 scales showed a statistically significant variation at one year compared to baseline (median CD-RISC25 64 at baseline vs 61 at follow-up; SEF 31 vs 30; SES 32.5 vs 32; PSS-IBD 0.45 vs 0.45). A statistically significant and inverse correlation was found between CD-RISC25 and PSS-IBD (rho -0.222, p=0.01), SEF and PSS-IBD (rho -0.219, p= 0.01), SES and PSS-IBD (-0.316, p=0.003). CD-RISC25 was found to be positively associated with inactive IBD (p=0.05).DiscussionIn this prospective study we have shown for the first time that stigmatisation, resilience, SEF and SEM did not change over a one-year time span, suggesting that, based on the information gathered, these characteristics may be independent from IBD severity or IBD flares. Furthermore, we found an inverse correlation of stigma with resilience, SEF and SES, suggesting an important role that these variables may have on preventing stigmatisation.

Study protocol for a pilot randomized, double-blind, placebo-controlled trial to investigate the anti-inflammatory effects of Frondanol in adults with inflammatory bowel disease

IntroductionInflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis, is a debilitating condition with a rising incidence globally over recent years. Frondanol, a widely available nutraceutical extract of the edible sea cucumber Cucumaria frondosa has been reported to possess potent anti-inflammatory effects, likely mediated by the inhibition of 5-lipoxygenase and 12-lipoxygenase pathways, whilst showing no signs of toxicity. The potent anti-inflammatory effects of Frondanol in a mouse model of IBD provide encouragement for investigating its effects in human IBD patients. Here we describe the study protocol of a pilot randomized, double-blinded, placebo-controlled trial of Frondanol in patients with mild to moderate IBD who are on standard therapy. Material and methodsOne hundred patients will be randomized (1:1) to receive Frondanol or placebo as an adjunct to their standard therapy for the period of six months. Blood and stool samples will be obtained during routine visits at baseline, and after three months and six months of treatment, and tissue samples from colon biopsies will be obtained during clinically indicated colonoscopies at baseline and after six months of treatment. The levels of inflammatory markers will be compared in serum and tissue samples between patients treated with Frondanol and those treated with placebo, and findings will be correlated with clinical and histological parameters. DiscussionIf proven beneficial, treatment with Frondanol may increase the likelihood of patients remaining in remission and potentially provide an effective, natural and safe addition/alternative for treatment-naive patients in the future.(Clinical trial registration number: NCT05194007).