Inactive Colitis Research Articles

Oxidative stress-related biomarkers as promising indicators of inflammatory bowel disease activity: A systematic review and meta-analysis

Oxidative stress is believed to play an important role in the pathogenesis of inflammatory bowel disease (IBD), specifically Crohn's disease (CD) and ulcerative colitis (UC). This meta-analysis aimed to identify and quantify the oxidative stress-related biomarkers in IBD and their associations with disease activity. We systematically searched Ovid MEDLINE, Ovid Embase, and Web of Science databases, identifying 54 studies for inclusion. Comparisons included: (i) active IBD versus healthy controls; (ii) inactive IBD versus healthy controls; (iii) active CD versus inactive CD; and (iv) active UC versus inactive UC. Our analysis revealed a significant accumulation of biomarkers of oxidative damage to biomacromolecules, coupled with reductions in various antioxidants, in both patients with active and inactive IBD compared to healthy controls. Additionally, we identified biomarkers that differentiate between active and inactive CD, including malondialdehyde, Paraoxonase 1, catalase, albumin, transferrin, and total antioxidant capacity. Similarly, levels of Paraoxonase 1, erythrocyte glutathione peroxidase, catalase, albumin, transferrin, and free thiols differed between active and inactive UC. Vitamins and carotenoids also emerged as potential disease activity biomarkers for CD and UC, but their intake should be monitored to obtain meaningful results. These findings emphasize the involvement of oxidative stress in the pathogenesis of IBD and highlight the potential of oxidative stress-related biomarkers as a minimally invasive and additional tool for monitoring the activity of IBD.

Evaluation of the Role of Serum Calprotectin in the Follow Up of Egyptian Inflammatory Bowel Disease Patients

Abstract Background The term inflammatory bowel disease (IBD) describes disorders in which the intestines be inflamed. It has often been thought that they are due to an autoimmune disease. Two major types of IBD are ulcerative colitis (UC) and Crohn's disease (CD). UC is limited to the colon. CD can involve every part of the gastrointestinal tract from the mouth to the anus. Objective To compare between serum and faecal calprotectin regarding their role in follow up of disease activity in inflammatory bowel disease patients. Patients and Methods An observational cross-sectional study was conducted on 25 patients admitted to Tropical medicine department, Ain Shams University Hospitals. Results Calprotectin is highly resistant to proteolysis and can hold in the stool sample for up to 7 days at room temperature. Higher levels of serum calprotectin were linked to a severe inflammatory state in the colon as well as significant clinical symptoms in UC patients. Also, serum calprotectin, CRP, and ESR levels were compared to IBD activity and it was detected that serum calprotectin levels had more sensitivity and specificity than CRP and ESR in identifying IBD activity. Serum calprotectin levels in patients with IBD activity either UC or CD groups, were considerably more than in remission. SC and FC levels were higher levels in clinically active IBD comparing with inactive IBD. Conclusion Serum calprotectin levels are higher in patients with IBD and are related to clinical activity. High serum calprotectin levels can distinguish between patients who are clinically active and those who are in remission in both UC and CD groups. Our findings show that serum calprotectin may be a promising simple diagnostic and prognostic biomarker for IBD however more research is needed to reach a judgment in this regard.

Obstetric outcomes of patients with inflammatory bowel disease.

Inflammatory bowel diseases (IBD) are frequently diagnosed between the ages of 20 and 40, i.e. the most fertile period for women. The potential impact of IBD on pregnancy is therefore a frequent issue. To determine the impact of disease activity during pregnancy on the obstetric prognosis of women with IBD. Gastroenterological and obstetric data were collected for patients for all consecutive patients with IBD and pregnancy followed up at Amiens University Hospital (Amiens, France) between 2007 and 2021. Obstetrics outcome of patients with and without active disease were compared. One hundred patients were included (81 with Crohn's Disease for 198 pregnancies, 19 with Ulcerative Colitis for 37 pregnancies). Patients with active IBD (21 patients, 24 pregnancies) were more likely to be admitted to hospital during pregnancy (66.6, vs. 5.2% in the inactive IBD group; p < 0.001), to give birth prematurely (mean term: 36.77 weeks of amenorrhoea (WA) vs. 38.7 WA, respectively; p = 0.02) and to experience very premature delivery (before 32 WA: 12.5 vs. 1.4%, respectively; p = 0.02). Patients with active disease had a shorter term at birth (38.4 WA, vs. 39.8 WA in the inactive disease group; p < 0.0001), a lower birth weight (2707 g vs. 3129 g, respectively; p = 0.01) and higher caesarean section rate (54.2 vs. 16.9%, respectively; p = 0.03). Women with IBD patients are at risk of pregnancy related complications, especially when IBD is active. Controlling disease activity at conception and close monitoring of the pregnancy is essential to improve both gastroenterological and obstetric outcome.

P151 Characterization of platelet activation profile in Inflammatory Bowel Disease

Abstract Background Platelet-related markers associated with a procoagulant state have been described for Immune-mediated Inflammatory Diseases (IMIDs), but a broader profiling of these abnormalities in Inflammatory Bowel Disease (IBD) is lacking. Methods Cross-sectional study to describe and compare platelet biomarkers of IBD outpatients, both Crohn’s Disease (CD) and Ulcerative Colitis (UC), vs healthy controls (HC). Patients over 18 years old with a diagnosis of CD or UC according to the European Crohn’s and Colitis Organization (ECCO) criteria were included. Fecal calproctectin (Fcal) &amp;gt;=150ug/g was used as a cutoff level for active disease. Exclusion criteria for IBD patients are listed under Table 1. Fibrinogen (FBG) receptor on platelet’s surface was determined with anti-CD41 and anti-CD61 monoclonal antibodies (mAbs); and von Willebrand factor receptor with anti-CD42a and anti-CD42b mAbs. Platelet activation markers [TRAP and ADP-induced activation of fibrinogen (FBG) receptor, and P-selectin (Psel) and CD63 exposure] were determined, respectively, through binding of PAC1, anti-P-selectin and anti-CD63 (mAbs). All variables were determined by flow cytometry. Results 55 patients (27 CD, 28 UC) and 75 HC have been included. 43 IBD patients had active disease (21 CD, 22 UC). Complete baseline characteristics of the IBD population are described in Table 1. Basal Psel (% of positive cells) was increased in CD vs UC (median [IQR]: 5.64 [4,4-10,4] vs 2,9 [1,8-6,8], p=0,02) and vs HC (3,5 [1,4-6,8], p=0,008). ADP-induced Psel was increased in CD vs HC (mean, SD: 49.92, SD 12.75 vs 41.943, SD13.15, p=0,007). Basal CD63 (% of positive cells) was significantly higher in active IBD vs HC (W = 1143, p = 0.02) and inactive IBD vs HC (W = 528, p= 0.006). CD42a (% of positive cells) was decreased in IBD vs HC (W = 1128.00, p=0.007) and CD vs HC (W = 777.00, p =0.04). CD42b (% of positive cells) was also decreased in IBD vs HC (mean, SD: 106.9 SD, 17.32 vs 115.7, SD 28.42, p=0,01) and CD vs HC (104.06 SD 14.49, p=0,03). No differences in basal or TRAP/ADP induced PAC binding, and in CD41 or CD61 expression were observed among groups. Multiple linear regression showed association of Fcal with basal Psel in IBD patients (p=0,02); and Spearman’s correlation showed negative moderate correlation between Fcal and basal Psel (r=0,3; p=0,003) Conclusion Features of platelets in IBD suggest increased platelet degranulation and reduced vWF receptor with regards to healthy controls, specially in CD, but no differences in FBG-related receptors. Inverse moderate correlation between Fcal and Psel in IBD patients suggests depletion of intra-platelet granules at higher levels of gut inflammation.

DOP45 Blood-derived neutrophils give rise to differentially activated populations in the mucosa of active Inflammatory Bowel Disease patients

Abstract Background Infiltration of neutrophils is the main histological feature in active inflammatory bowel disease (IBD). Recent data suggests that tissue- and tumour-infiltrating neutrophils can adopt remarkably different phenotypes with potentially different functions. However, the heterogeneity of this population in IBD remains unknown. Methods Single-cell RNA sequencing (scRNA-seq) data was generated from colonic biopsies of 92 individuals including 6 healthy controls (HC), 36 inactive IBD, 19 active Crohn’s disease (CD) and 31 active ulcerative colitis (UC) patients. Neutrophils (6038 cells) found in the inflamed colon of CD and UC patients were analysed using a curated pipeline in Seurat (v4.0.2)1. Posterior analysis included the FindAllMarkers function (differentially expressed genes), Jaccard index similarity and the AddModuleScore function (comparisons with literature-described neutrophils), Monocle3 algorithm (developmental trajectory) and clusterProfiler (v3.0.4; enrichment and pathway analysis). For in vitro stimulation, neutrophils were isolated from the blood of HC donors (n=4) using a double Ficoll gradient 1. Cells and supernatants were analysed for qPCR and ELISA determinations. Results We identified 6 different clusters/states of colonic neutrophils (Figure 1A). In agreement with our previous results1 we found a population of S100A12/S100A8/S100A9 neutrophils (N0), IFN-response neutrophils (N3) and CCL3/CCL4 neutrophils (N2), in addition to N1.1 and N1.2 neutrophils. N3 neutrophils were enriched in the inflamed colon of CD patients compared to UC (17.2% vs 5.8%, p-value= 0.0021; Figure 1C). Comparative analysis with published datasets revealed that N0, N1.2 and N3 resemble populations of neutrophils found in blood2,3. In contrast, N1.1 and N2-like clusters showed some similarity to umbilical cord blood3 and tumour-infiltrating neutrophils4. Trajectory analysis, originating from N0 (peripheral-like) neutrophils, showed two potential branches of differentiation, with N1.2 leading towards N3 (IFN-response) and N1.1 differentiating into N2 (CCL3) neutrophils (Figure 1B). Finally, pathway analysis showed that N2 neutrophils presented enriched gene expression of the TNF signalling pathway, and together with the N1.1 state, an enrichment of the IL1β signalling pathway as well. In vitro experiments revealed that TNF, IL1β and LPS can all induce expression of CCL3 and CCL4, top differentially expressed genes of N2 neutrophils. Conclusion We show that active IBD is associated with a highly heterogeneous population of infiltrating neutrophils. Some of them resemble neutrophils in peripheral blood, while others most likely differentiate in response to inflammatory cues present in the colon of active IBD patients.

Plasma Extracellular Vesicle LncRNA H19 as a Potential Diagnostic Biomarker for Inflammatory Bowel Diseases.

Inflammatory bowel disease (IBD) is a complex gastrointestinal disease with 2 main subtypes of Crohn's disease (CD) and ulcerative colitis (UC), whose diagnosis mainly depends on the medical history, clinical symptoms, endoscopic, histologic, radiological, and serological findings. Extracellular vesicles (EVs) are now considered an additional mechanism for intercellular communication, allowing cells to exchange biomolecules. Long noncoding RNAs (lncRNAs) that are enriched in EVs have been defined as an ideal diagnostic biomarker for diseases. In this study, we investigated the expression differences of 5 lncRNAs in tissue and plasma EVs of active IBD patients compared with patients in the remission phase and healthy controls to introduce an EV-lncRNA as a noninvasive IBD diagnostic biomarker. Twenty-two active IBD patients, 14 patients in the remission phase, 10 active rheumatoid arthritis (RA) patients, 14 irritable bowel syndrome (IBS) patients, and 22 healthy individuals were recruited in the discovery cohort. In addition, 16 patients with active IBD, 16 healthy controls, 10 inactive IBD patients, 12 active RA patients, and 14 IBS patients were also included in the validation cohort. The expression levels of 5 lncRNAs in tissue and EV-plasma were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) . Machine learning and receiver operating characteristic (ROC) curve analysis were performed to investigate the distinguishing ability of the candidate biomarkers. While the expression levels of lncRNAs CDKN2B-AS1, GAS5, and TUG1 were significantly downregulated, lncRNAs H19 and CRNDE were overexpressed in active IBD lesions. Expression of H19 was detected in plasma EVs whose isolation had been confirmed via dynamic light scattering, microscopy images, and western blotting. The classification results demonstrated the excellent ability of H19 in distinguishing IBD/active from IBD/remission, healthy control, RA, and IBS (area under the ROC curve = 0.95, 0.97,1, and 0.97 respectively). Our study suggests that circulating EV-lncRNA H19 exhibited promising potential for the diagnosis of active IBD.

S1102 Colonoscopy Prep Is Associated With Increased Risk of Flare Among Patients With Previously Inactive Inflammatory Bowel Disease

S1102 Colonoscopy Prep Is Associated With Increased Risk of Flare Among Patients With Previously Inactive Inflammatory Bowel Disease

Utility of Geboes score for assessing histological activity in ulcerative colitis

Introduction and Aim: Diagnosis of UC is challenging and calls for an integrated clinical, endoscopic, serological, and histological examination. Although inexpensive and non-invasive, endoscopic findings do not always correlate with disease activity, as demonstrated by traditional histopathological examination. Materials and Methods: This retrospective study was conducted between January 2014 and December 2019. Specimens of patients diagnosed with UC that were received in the Department of Pathology were included. An experienced pathologist assessed the histological disease activity using the Geboes score. The Mayo endoscopic subscore was recorded for endoscopic activity. Results thus obtained were entered into MS Excel and analysis was done using SPSS version 25.0. Results: Of the 123 cases of UC, (age, 14 to 74 years; males: 60.2%, females: 39.8%) majority had endoscopic findings of erythema and edema (n=20) with the least common finding being ileocolitis (n=1). Mayo subscore was available in 24 cases (ranging from 1 to 3; Mayo subscores of 1, 2, and 3 in 1, 14 and 9 cases respectively). Active colitis was noted in 78% (96/123) of the patients while the remaining 22% (27/123) of patients had inactive colitis. Only 24 cases had both Mayo subscore and Geboes score correlation. Fourteen cases had a Mayo subscore of 2 and a Geboes score ranging from 2A to 5.2; 9 cases had a Mayo subscore of 3 and a Geboes score ranging from 4.1 to 5.2. Conclusion: Assessment of histological disease activity by Geboes score provides useful information in routine reporting of biopsy specimens of cases of Ulcerative colitis

Association of serum lipids with inflammatory bowel disease: a systematic review and meta-analysis.

Serum lipid levels seem to be abnormal in Inflammatory bowel disease (IBD). However, the specific manifestation of abnormal serum lipid levels in IBD are heterogeneous among studies and have not been sufficiently determined yet. PubMed, EMBASE, and Cochrane Library databases were searched. Serum lipid levels were compared between IBD patients and Health individuals, Crohn's (CD) and ulcerative colitis (UC), active and inactive, mild and non-mild patients, respectively. Meta-analyses were performed by using a random-effect model. Weight mean difference (WMD) with 95% confidence intervals (CIs) were calculated. Overall, 53 studies were included. Compared with healthy controls, IBD patients had significantly lower TC (WMD = -0.506, 95%CI = -0.674 to -0.338, p < 0.001), HDL-c (WMD = -0.122, 95%CI = -0.205 to -0.039, p = 0.004), and LDL-c (WMD = -0.371, 95%CI = -0.547 to -0.194, p < 0.001) levels. CD groups had a significantly lower TC (WMD = -0.349, 95%CI = -0.528 to -0.170, p < 0.0001) level as compared to UC groups. Active IBD and non-mild UC groups had significantly lower TC (WMD = -0.454, 95%CI = -0.722 to -0.187, p = 0.001) (WMD =0.462, 95%CI = 0.176 to 0.748, p = 0.002) and LDL-c (WMD = -0.225, 95%CI = -0.445 to -0.005, p = 0.045) (WMD =0.346, 95%CI = 0.084-0.609, p = 0.010) levels as compared to inactive IBD and mild UC groups, respectively. The overall level of serum lipids in IBD patients is lower than that of healthy individuals and is negatively associated with disease severity. https://www.crd.york.ac.uk/prospero/, identifier: CRD42022383885.

Fatigue in patients with inflammatory bowel disease—strongly influenced by depression and not identifiable through laboratory testing: a cross-sectional survey study

BackgroundFatigue is a debilitating and highly relevant symptom in patients with inflammatory bowel disease (IBD). However, awareness of fatigue and treatment options remains limited. This study was aimed at elucidating the influence of disease activity and common complications (pain, anemia, depression, anxiety and quality of life) on fatigue in patients with IBD to identify potential interventional targets for treating physicians.MethodsA cross-sectional survey including five questionnaires (HADS, Fatigue Assessment Scale, McGill Pain Questionnaire, IBDQ and general well-being) was performed on patients with IBD (n = 250) at a university IBD clinic. Additionally, demographic data, laboratory data, IBD history, treatment and current disease activity (Harvey-Bradshaw Index, partial Mayo Score, calprotectin and CRP) were recorded.ResultsA total of 189 patients were analyzed (59.8% with Crohn’s disease (CD) and 40.2% with ulcerative colitis (UC)). A total of 51.3% were fatigued, and 12.2% were extremely fatigued. Multiple factors showed significant correlations in univariate analysis. Multivariate analysis revealed that fatigue was correlated with depression (CD, p = 0.002; UC, p = 0.02), diminished quality of life (CD, p = 0.015), female sex (CD, p = 0.015) and younger age (UC, p = 0.024), whereas the influence of anemia or disease activity was non-significant.ConclusionsFatigue is burdensome and highly prevalent in patients with active and inactive IBD. Considerations for fatigue treatment, beyond targeting inflammation and anemia, should include investigation of underlying sub-clinical depression.

The Association Between Depression and Activity of Inflammatory Bowel Disease

Background: The association between depression and inflammatory bowel disease (IBD) has been reported worldwide. Objectives: We aimed to investigate the prevalence of active and inactive IBD depression and its associated risk factors among patients with depression and IBD. Materials &amp; Methods: In this cross-sectional study, demographic data and clinical characteristics of 156 IBD patients referred to Razi Hospital, Rasht City, Iran, were recorded from 2015 to 2016. The Beck depression inventory (BDI) was administered to all patients, and their scores were classified as no, mild, moderate, and severe depression. Modified Truelove and Witts severity index (MTWSI) for ulcerative colitis (UC) and Harvey Bradshaw severity index (HBSI) for Crohn’s disease (CD) were used to quantitate IBD activity as active UC (scored ≥10) and active CD (scored ≥7). Results: About 35.9% of the patients (n=56) had depression. Patients with active IBD had significantly higher BDI scores than those with inactive IBD (14.41±10.34 vs 10.14±10.28, respectively, P=0.011). Except for income (P=0.001), no significant associations were detected between IBD status and other background variables (P&gt;0.05). No patients in either active or inactive IBD groups had cancers. Based on the severity of depression, the patients were grouped as follows: 64.1% had no depression, 30.1% had mild depression, 5.8% had moderate depression, and 0.0% had severe depression. However, significant positive associations were seen between an increase in depression severity and having autoimmune diseases, a lower education level, and a history of IBD-related surgeries. Conclusion: It seems that patients with active IBD are more depressed than inactive IBD patients.

Fatigue Is Associated with Anxiety and Lower Health-Related Quality of Life in Patients with Inflammatory Bowel Disease in Remission.

Background and Objectives: Inflammatory bowel diseases (IBD) are chronic conditions with an unpredictable course and a remitting-relapsing evolution. Fatigue is a frequent complaint in patients with IBD, affecting approximately half of the newly diagnosed patients with IBD. The aim of this study was to analyze fatigue in patients with IBD in remission. Materials and Methods: One hundred nineteen consecutive outpatients diagnosed with IBD for over 3 months that were in corticosteroid-free clinical and biochemical remission at the time of assessment were included in this cross-sectional study. Out of them, 72 (60.5%) were male; the median age was 39 years (IQR 30-47). Seventy-seven patients (64.7%) were diagnosed with Crohn's disease and forty-two (35.3%) with ulcerative colitis, with a median disease duration of 6 years (IQR 2-10). Fatigue, health-related quality of life (HR-QoL), anxiety and depression were evaluated using the following self-administered questionnaires: FACIT Fatigue, IBDQ 32 and HADS. Results: The mean FACIT-Fatigue score was 41.6 (SD ± 8.62), and 38.7% of patients were revealed as experiencing fatigue when a cut-off value of 40 points was used. The mean IBDQ 32 score was 189.4 (SD ± 24.1). Symptoms of anxiety and depression were detected in 37% and 21% of the patients, respectively. In the multivariate analysis, fatigue was significantly associated with lower HR-QoL (OR 2.21, 95% CI: 1.42-3.44, p < 0.001), symptoms of anxiety (OR 5.04, 95% CI: 1.20-21.22, p = 0.008), female sex (OR 3.32, 95% CI: 1.02-10.76, p = 0.04) and longer disease duration (OR 1.13, 95% CI: 1.01-1.27, p = 0.04). Conclusions: Fatigue is highly prevalent even in patients with inactive IBD and is correlated with lower HR-QoL and anxiety, as well as with clinical factors such as longer disease duration and female sex.

A138 SERRATED POLYPOSIS SYNDROME IN INFLAMMATORY BOWEL DISEASE: A SEQUELAE OF CHRONIC DISEASE ACTIVITY OR NEW WHO PHENOTYPE?

Abstract Background Serrated polyposis syndrome (SPS) is a growing health concern with up to 1 in 125 universal screening program participants meeting diagnostic criteria. Conversely, SPS in inflammatory bowel disease (IBD) is rarely described in the literature, despite the predisposition for serrated epithelial change and serrated polyps in this population. Purpose To describe a case of World Health Organization (WHO) criterion I SPS in a patient with IBD, and discuss the existing literature on this rare occurrence. Method Case report and review of the literature. Result(s) Case Report A 53-year-old female with ulcerative colitis (UC; Phenotype: Left-sided; Duration of disease: 40 years; Medical therapy: sulfasalazine) undergoing regular endoscopic surveillance was recently found to have multiple serrated-class lesions including 6 in the sigmoid colon ranging between 8-30mm in size; this included 3 sessile serrated lesions (SSLs) between 20-30mm removed by piecemeal cold snare resection without complication and 2 residual large SSLs for staged endoscopic resection. No endoscopic disease activity was appreciated (Mayo 0), with histopathology of the sigmoid colon and rectum demonstrating chronic inactive colitis. Literature Review From 2008 to 2021, there are eleven reported cases of SPS in IBD. Six patients had UC and most were in remission for several decades at the time of SPS diagnosis. Most SPS cases met WHO criteria and fit within described phenotypes. While the case above meets WHO criterion I for SPS, the presence of large distal lesions is atypical, raising the question of whether chronic disease activity contributed to the development of these serrated lesions, given the known predisposition for serrated epithelial change and serrated lesions in patients with colonic IBD. Image Conclusion(s) SPS in patients with IBD is rare. Questions remain about the role of chronic disease activity contributing to the formation of serrated lesions, its clinical relevance, and optimal management strategy. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

P383 Real-life experience of the efficacy, safety and pharmacokinetic data of switching from intravenous to subcutaneous infliximab in inactive inflammatory bowel disease patients. Results from the ENEIDA registry.

Abstract Background Recently, a subcutaneous formulation of biosimilar infliximab (CT-P13) (SC-IFX) has been approved for inflammatory bowel disease (IBD). The aims of this study were to evaluate efficacy, safety, pharmacokinetics and patient experience following a switching to SC-IFX in patients who are in clinical remission on IV-IFX maintenance treatment. Methods Multicentre, descriptive, and observational study including Crohn’s disease (CD) and ulcerative colitis (UC) patients who were going to be changed from IV-IFX to SC-IFX on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD–GETECCU). All patients were on clinical and biological remission at least 24 weeks before changing. Demographic and disease data, clinical activity (Harvey-Bradshaw index for CD and mayo index for UC), analytical data (C reactive protein (CRP) and fecal calprotectin (FC), as well as trough levels were collected at baseline, at 12 and 24 weeks. Results One hundred and fifty-five patients were included: 54 UC (35%) and 91 (65%) CD; 44% women and 56% men; age 45.5 years (32-55). IV-IFX was mainly administered due to active disease (72%) and perianal disease (7%) and during 32 months [range 14-56]. Pre-switch, 78 (50.3%) were on 8-weekly dosing of IV-IFX, 77 (49.7%) were with intensification dose and the half (50.3%) were on concomitant immunomodulatory therapy. SC-IFX was mainly switching by COVID-19 pandemic (60%), to increase through levels (15%) or patient request (25%). The majority of patients (140, 90%) remained with standard dose, 8 (5%) required dose intensification (120 mg weekly in 4 and 240 mg every 2 weeks in 4) and 7 (4.5%) had successful de-escalation (120 mg every 3 weeks in 4 and 120 mg every 4 weeks in 3). Clinical indices, CRP levels and FC remained unchanged (Figure). Median SC-IFX levels significantly increased from baseline of 4.5 μg/dl [range 2.6-9.2] to 14 μg/dl [range 9.5-16.2] at week 12 and 13.2 μg/dl [range 10.4-19.7] at week 24. No factors (immunossupresor, body mass index, disease location) were associated with the increase of IFX trough levels. During 24 weeks of follow-up, 16 of the 78 patients (20.5%) stopped immunosuppressant treatment. The adverse events were recorded in 9 patients (5.8%), 4 (2.6%) were hospitalized and 4 (2.6%) had surgery (one of them for perianal disease). Nine patients (5.8%) stopped SC-IFX (1 primary failure, 2 loss of response, 4 adverse events, 1 voluntarily, and 1 surgery). Conclusion The switch from IV to SC IFX maintains clinical remission safely in IBD patients, offers higher drug levels and a good patient acceptance. However, the significance of higher drug levels with SC-IFX requires further exploration.

The Importance of Nutritional Aspects in the Assessment of Inflammation and Intestinal Barrier in Patients with Inflammatory Bowel Disease.

Intestinal inflammation in inflammatory bowel disease (IBD) is closely linked to nutrition. This study aimed to evaluate associations between nutritional, inflammatory, and intestinal barrier parameters in patients with IBD. We assessed nutritional status, fecal short-chain fatty acid profile, serum cytokine levels, and mRNA expression of enzymes and tight junction proteins in intestinal biopsies obtained from 35 patients, including 11 patients with inactive IBD, 18 patients with active IBD, and six controls. Patients with active IBD were characterized by hypoalbuminemia, fluctuations in body weight, and restriction of fiber-containing foods. In addition, they had significantly reduced levels of isovaleric acid and tended to have lower levels of butyric, acetic, and propionic acids. Patients with active IBD had higher mRNA expression of peroxisome proliferator-activated receptor γ and inducible nitric oxide synthase, and lower mRNA expression of claudin-2 and zonula occludens-1, compared with patients with inactive IBD. Moreover, patients with a body mass index (BMI) of ≥25 kg/m2 had higher median tumor necrosis factor-α levels that those with a lower BMI. We comprehensively evaluated inflammatory parameters in relation to IBD activity and nutritional status. The discrepancies between proinflammatory and anti-inflammatory parameters depending on IBD activity may be related to nutritional factors, including diet and abnormal body weight.

Systematic review and meta-analysis of sleep quality in inactive inflammatory bowel disease.

Poor sleep in people with inflammatory bowel disease (IBD) has been demonstrated to be prevalent and has been associated with disease activity. This meta-analysis aimed to assess the prevalence of poor sleep in inactive IBD and in controls by considering cohort and cross-sectional studies. Electronic databases were searched for publications from inception to 1 November 2021. Poor sleep and IBD activity were defined according to self-reported subjective sleep measures. A random effects model was used to determine the standardized mean difference between poor sleep in inactive IBD and healthy controls. Publication bias was assessed by funnel plot and Egger's test. Five hundred and nineteen studies were screened with 9 studies included in the meta-analysis incorporating a total of 729 people with IBD and 508 controls. A random effects model showed a standardized mean difference with poor sleep being more frequent in those with inactive IBD than controls with moderate effect size (Hedge's g 0.41, CI [0.22-0.59]) and no significant heterogeneity. There was no publication bias evident. Poor sleep is more common in individuals with inactive IBD than healthy controls. Further studies should consider potential mechanisms to explain this result, including the role of subclinical inflammation and psychosocial factors that may influence sleep quality in people with IBD.

Unfermented β-fructan Fibers Fuel Inflammation in Select Inflammatory Bowel Disease Patients

Inflammatory bowel diseases (IBD) are affected by dietary factors, including nondigestible carbohydrates (fibers), which are fermented by colonic microbes. Fibers are overall beneficial, but not all fibers are alike, and some patients with IBD report intolerance to fiber consumption. Given reproducible evidence of reduced fiber-fermenting microbes in patients with IBD, we hypothesized that fibers remain intact in select patients with reduced fiber-fermenting microbes and can then bind host cell receptors, subsequently promoting gut inflammation. Colonic biopsies cultured exvivo and cell lines invitro were incubated with oligofructose (5 g/L), or fermentation supernatants (24-hour anaerobic fermentation) and immune responses (cytokine secretion [enzyme-linked immunosorbent assay/meso scale discovery] and expression [quantitative polymerase chain reaction]) were assessed. Influence of microbiota in mediating host response was examined and taxonomic classification of microbiota was conducted with Kraken2 and metabolic profiling by HUMAnN2, using R software. Unfermented dietary β-fructan fibers induced proinflammatory cytokines in a subset of IBD intestinal biopsies cultured exvivo, and immune cells (including peripheral blood mononuclear cells). Results were validated in an adult IBD randomized controlled trial examining β-fructan supplementation. The proinflammatory response to intact β-fructan required activation of the NLRP3 and TLR2 pathways. Fermentation of β-fructans by human gut whole microbiota cultures reduced the proinflammatory response, but only when microbes were collected from patients without IBD or patients with inactive IBD. Fiber-induced immune responses correlated with microbe functions, luminal metabolites, and dietary fiber avoidance. Although fibers are typically beneficial in individuals with normal microbial fermentative potential, some dietary fibers have detrimental effects in select patients with active IBD who lack fermentative microbe activities. The study is publicly accessible at the U.S. National Institutes of Health database (clinicaltrials.gov identification number NCT02865707).

The Impact of Disease Activity on Sexual and Erectile Dysfunction in Patients With Inflammatory Bowel Disease.

Increased disease activity may be a risk factor for sexual dysfunction (SD) in patients with inflammatory bowel disease (IBD). This study investigated associations between objective measures of disease activity and sexual function. Adults with IBD undergoing ileocolonoscopy were prospectively recruited. Demographic, sexual function (Female Sexual Function Index and International Index of Erectile Function), disease activity (endoscopic, biomarker, and symptoms), psychological symptoms, and quality-of-life data were collected. Rates of SD and erectile dysfunction (ED) were compared between patients with active and inactive inflammation and symptoms using the Fisher's exact test. Logistic regression examined associations between SD and ED, and disease characteristics and psychological symptoms. A total of 159 participants were included, 97 had Crohn's disease and 85 were women. SD was reported in 36 of 59 and 13 of 59 sexually active women and men, respectively and ED in 22 of 59 sexually active men. Rates of SD and ED were similar between individuals with active and inactive IBD based on endoscopic indices (P > .05) and biomarkers (P > .05). Women with active IBD symptoms experienced significantly higher rates of SD (P < .05), but men did not (P > .05). Multivariable logistic regression identified that symptoms of severe depression (odds ratio, 5.77; 95% confidence interval, 1.59-20.94) were associated with SD in women, and severe anxiety (odds ratio, 15.62; 95% confidence interval, 1.74-140.23) was associated with ED in men. Objective measures of disease activity are not associated with SD or ED in patients with IBD. Clinicians should consider concomitant psychological symptoms contributing to the sexual health of patients with IBD.

Prevalence and factors associated with vitamin C deficiency in inflammatory bowel disease.

BACKGROUNDPatients with inflammatory bowel disease (IBD) are prone to several nutritional deficiencies. However, data are lacking on vitamin C deficiency in Crohn’s disease (CD) and ulcerative colitis (UC) patients, as well as the impact of clinical, biomarker and endoscopic disease severity on the development of vitamin C deficiency.AIMTo determine proportions and factors associated with vitamin C deficiency in CD and UC patients.METHODSIn this retrospective study, we obtained clinical, laboratory and endoscopic data from CD and UC patients presenting to the IBD clinic at a single tertiary care center from 2014 to 2019. All patients had an available plasma vitamin C level. Of 353 subjects who met initial search criteria using a cohort discovery tool, 301 ultimately met criteria for inclusion in the study. The primary aim described vitamin C deficiency (≤ 11.4 μmol/L) rates in IBD. Secondary analyses compared proportions with deficiency between active and inactive IBD. Multivariate logistic regression analysis evaluated factors associated with deficiency.RESULTSOf 301 IBD patients, 21.6% had deficiency, including 24.4% of CD patients and 16.0% of UC patients. Patients with elevated C-reactive protein (CRP) (39.1% vs 16.9%, P < 0.001) and fecal calprotectin (50.0% vs 20.0%, P = 0.009) had significantly higher proportions of deficiency compared to those without. Penetrating disease (P = 0.03), obesity (P = 0.02) and current biologic use (P = 0.006) were also associated with deficiency on univariate analysis. On multivariate analysis, the objective inflammatory marker utilized for analysis (elevated CRP) was the only factor associated with deficiency (odds ratio = 3.1, 95% confidence interval: 1.5-6.6, P = 0.003). There was no difference in the presence of clinical symptoms of scurvy in those with vitamin C deficiency and those without.CONCLUSIONVitamin C deficiency was common in IBD. Patients with elevated inflammatory markers and penetrating disease had higher rates of vitamin C deficiency.

Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial

Fatigue is highly prevalent among patients with inflammatory bowel disease (IBD), and only limited treatment options are available. Based on the hypothetical link between low serum tryptophan concentrations and fatigue, we determined the effect of 5-hydroxytryptophan supplementation on fatigue in patients with inactive IBD. A multicenter randomized controlled trial was performed at 13 Belgian hospitals, including 166 patients with IBD in remission but experiencing fatigue, defined by a fatigue visual analog scale (fVAS) score of ≥5. Patients were treated in a crossover manner with 100 mg oral 5-hydroxytryptophan or placebo twice daily for 2 consecutive periods of 8 weeks. The primary end point was the proportion of patients reaching a ≥20% reduction in fVAS after 8 weeks of intervention. Secondary outcomes included changes in serum tryptophan metabolites, Functional Assessment of Chronic Illness Therapy Fatigue scale, and scores for depression, anxiety, and stress. The effect of the intervention on the outcomes was evaluated by linear mixed modeling. During 5-hydroxytryptophan treatment, a significant increase in serum 5-hydroxytryptophan (estimated mean difference, 52.66 ng/mL; 95% confidence interval [CI], 39.34-65.98 ng/mL; P < .001) and serotonin (3.0 ng/mL; 95 CI, 1.97-4.03 ng/mL; P < .001) levels was observed compared with placebo. The proportion of patients reaching ≥20% reduction in fVAS was similar in placebo- (37.6%) and 5-hydroxytryptophan (35.6%)-treated patients (P= .830). The fVAS reduction (-0.18; 95% CI,-0.81 to 0.46; P= .581) and Functional Assessment of Chronic Illness Therapy Fatigue scale increase (0.68; 95% CI,-2.37 to 3.73; P= .660) were both comparable between 5-hydroxytryptophan and placebo treatment as well as changes in depression, anxiety, and stress scores. Despite a significant increase in serum 5-hydroxytryptophan and serotonin levels, oral 5-hydroxytryptophan did not modulate IBD-related fatigue better than placebo. (Trial Registration: Belgian Federal Agency for Medication and Health Products, EudraCT number: 2017-005059-10 and ClinicalTrials.gov: NCT03574948, https://clinicaltrials.gov/ct2/show/NCT03574948.).