Quiescent Crohn's Disease Patients Research Articles

Why Symptoms Linger in Quiescent Crohn's Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways.

Even in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with (qCD + S) vs without persistent GI symptoms (qCD-S). Thus, we hypothesized that sulfur metabolic pathways would be enriched in stool while differentially abundant microbes would be associated with important sulfur metabolic pathways in qCD + S. We performed a multicenter observational study nested within SPARC IBD. Quiescent inflammation was defined by fecal calprotectin level < 150 mcg/g. Persistent symptoms were defined by CD-PRO2. Active CD (aCD) and non-IBD diarrhea-predominant irritable bowel syndrome (IBS-D) were included as controls. Thirty-nine patients with qCD + S, 274 qCD-S, 21 aCD, and 40 IBS-D underwent paired shotgun metagenomic sequencing and untargeted metabolomic profiling. The fecal metabolome in qCD + S was significantly different relative to qCD-S and IBS-D but not aCD. Patients with qCD + S were enriched in sulfur-containing amino acid pathways, including cysteine and methionine, as well as serine, glycine, and threonine. Glutathione and nicotinate/nicotinamide pathways were also enriched in qCD + S relative to qCD-S, suggestive of mitochondrial dysfunction, a downstream target of H2S signaling. Multi-omic integration demonstrated that enriched microbes in qCD + S were associated with important sulfur metabolic pathways. Bacterial sulfur metabolic genes, including CTH, isfD, sarD, and asrC, were dysregulated in qCD + S. Finally, sulfur metabolites with and without sulfidogenic microbes showed good accuracy in predicting the presence of qCD + S. Microbial-derived sulfur pathways and downstream mitochondrial function are perturbed in qCD + S, which implicate H2S signaling in the pathogenesis of this condition. Future studies will determine whether targeting H2S pathways results in improved quality of life in qCD + S.

Why Symptoms Linger in Quiescent Crohn's Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways.

Even in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with ( qCD+S ) vs. without persistent GI symptoms ( qCD-S ). Thus, we hypothesized that sulfur metabolic pathways would be enriched in stool while differentially abundant microbes would be associated with important sulfur-metabolic pathways in qCD+S. We performed a multi-center observational study nested within SPARC IBD. Quiescent inflammation was defined by fecal calprotectin level <150 mcg/g. Persistent symptoms were defined by CD-PRO2. Active CD ( aCD ) and non-IBD diarrhea-predominant irritable bowel syndrome ( IBS-D ) were included as controls. Thirty-nine patients with qCD+S, 274 qCD-S, 21 aCD, and 40 IBS-D underwent paired shotgun metagenomic sequencing and untargeted metabolomic profiling. The fecal metabolome in qCD+S was significantly different relative to qCD-S and IBS-D but not aCD. Patients with qCD+S were enriched in sulfur-containing amino acid pathways, including cysteine and methionine, as well as serine, glycine, and threonine. Glutathione and nicotinate/nicotinamide pathways were also enriched in qCD+S relative to qCD-S, suggestive of mitochondrial dysfunction, a downstream target of H 2 S signaling. Multi-omic integration demonstrated that enriched microbes in qCD+S were associated with important sulfur-metabolic pathways. Bacterial sulfur-metabolic genes, including CTH , isfD , sarD , and asrC , were dysregulated in qCD+S. Finally, sulfur metabolites with and without sulfidogenic microbes showed good accuracy in predicting presence of qCD+S. Microbial-derived sulfur pathways and downstream mitochondrial function are perturbed in qCD+S, which implicate H 2 S signaling in the pathogenesis of this condition. Future studies will determine whether targeting H 2 S pathways results in improved quality of life in qCD+S. What is Already Known Even in the absence of inflammation, persistent gastrointestinal symptoms are common in Crohn's disease.The microbiome is altered in quiescent Crohn's disease patients with persistent symptoms, but the functional significance of these changes is unknown. What is New Here Sulfur metabolites and sulfur metabolic pathways were enriched in stool in quiescent Crohn's disease patients with persistent symptoms.Multi-omic integration showed enriched microbes were associated with important sulfur metabolic pathways in quiescent Crohn's disease patients with persistent symptoms. How Can This Study Help Patient Care Strategies to decrease sulfidogenic microbes and associated sulfur metabolic pathways could represent a novel strategy to improve quality of life in quiescent Crohn's disease with persistent GI symptoms.

Amino acid profiles, disease activity, and protein intake in adult patients with Crohn's disease.

Crohn's disease (CD) is an immune-mediated inflammatory disorder of the gastrointestinal tract with a relapsing-remitting course. Amino acids (AAs) may play critical roles in the intestinal manifestations of disease, due to their involvement in many metabolic and immune functions. The present study aimed to explore serum AA concentrations in adult patients with CD, looking into their variations due to disease activity, surgery and protein content of diet. Eventually, the link between AAs and inflammatory markers was also assessed. Consecutive adult patients aged 18-65 years with diagnosis of CD were recruited. All participants underwent anthropometry and were instructed to fill in a 3-day food record to assess protein intake. Disease activity was clinically defined using the Crohn's Disease Activity Index (CDAI), while blood samples were taken to analyze serum AA profile and inflammatory markers. A total of 103 patients with CD (61 men and 42 women; age:39.9 ± 13.9 years, BMI: 23.4 ± 3.51 kg/m2) were included. Tryptophan levels were found to be remarkably decreased in most subjects, unrelated to disease activity. On the contrary, concentration of lysine, leucine, valine and glutamine decreased in active versus quiescent CD patients, while aspartic acid, glutamate and glycine increased. The latter AAs were also directly correlated with CDAI and serum interleukin (IL)- 1β concentration. Considering the total protein intake, expressed as g/kg/body weight, we observed a reduction in some essential AAs in patients with unmet protein requirements compared to patients who met the recommendation. In conclusion, specific AAs varied according to disease activity and protein intake, adjusted to body weight and disease status. Glu and Asp concentrations raised with increasing IL-1β. However, extensive research is needed to understand the mechanisms underpinning the link between variation in serum AAs, disease activity and protein intake in patients with CD.

P188 Middle small-bowel segment Lewis score may predict long-term outcomes among patients with quiescent Crohn’s disease

Abstract Background Video capsule endoscopy (VCE) has been proven to accurately diagnose small-bowel inflammation and predict flares among patients with quiescent Crohn’s disease (CD). In this study we aimed to predict worse clinical outcomes over an extended follow-up. Methods This was a post-hoc analysis of adult patients with quiescent small-bowel CD who were followed with VCE, inflammatory biomarkers and magnetic resonance enterography (MRE) in a prospective study (between 2013-2018). We extracted extended clinical data from our hospital electronic health records to include the most recent follow-up (until Apr 2022). The primary composite outcome was clinical exacerbation defined as either intestinal-surgery, endoscopic dilation, CD-related admission, need for corticosteroids or biological/immunomodulator treatment change during the follow-up. Results Out of the 61 patients who were included in the study (median age of 29 [24-37] years, male–57.4%, current biologic treatment–46.7%), 18 patients met the composite outcome during an extended long-term follow-up (median of 58 [interquartile range 35-93] months). On univariable analysis, complicated (Hazard ratio [HR] 7.348, p=0.002) and stricturing disease-phenotype (HR 5.305, p=0.001) were associated with higher risk for clinical exacerbation during follow-up. A baseline VCE middle small-bowel segment Lewis score (midLS) of≥135 identified patients with future exacerbation (AUC of 0.767, 95% CI 0.633-0.902, p=0.001, HR 6.317, negative predictive value [NPV] of 93%), while the conventional Lewis score had an AUC of 0.734 (CI 0.589-0.879, p=0.004). Performing sensitivity analysis restricted to patients with either complicated (n=34) or stricturing disease-phenotype (n=26), we revealed that midLS still predicted disease exacerbation during the extended follow-up (AUC of 0.747 and 0.753, respectively) in these patients. Conclusion MidLS predicts treatment failure in quiescent Crohn's disease patients (median follow-up 5 years) independently of disease-phenotype.

Middle small-bowel segment Lewis score may predict long-term outcomes among patients with quiescent Crohn's disease.

Video capsule endoscopy (VCE) has been proven to accurately diagnose small-bowel inflammation and predict flares among patients with quiescent Crohn's disease (CD). However, data regarding its predictive role in this population over an extended follow-up are scarce. To predict clinical exacerbation and to assess the yield of Lewis score in identifying CD patients with future clinical exacerbation during an extended follow-up (>24 months). A post hoc analysis study. Adult patients with quiescent small-bowel CD who were followed with VCE, inflammatory biomarkers and magnetic resonance enterography in a prospective study (between 2013 and 2018). We extracted extended clinical data (up to April 2022). The primary composite outcome (i.e. clinical exacerbation) was defined as intestinal surgery, endoscopic dilation, CD-related admission, corticosteroid administration, or biological/immunomodulator treatment change during follow-up. Of the 61 patients in the study [median age 29 (24-37) years, male 57.4%, biologic treatment 46.7%], 18 patients met the primary outcome during an extended follow-up [median 58.0 (34.5-93.0) months]. On univariable analysis, complicated [hazard ratio (HR) 7.348, p = 0.002] and stricturing disease phenotype (HR 5.305, p = 0.001) were associated with higher risk for clinical exacerbation during follow-up. A baseline VCE middle small-bowel segment Lewis score (midLS) ⩾ 135 identified patients with future exacerbation [AUC (area under the curve) 0.767, 95% confidence interval (CI) 0.633-0.902, p = 0.001, HR 6.317, 93% negative predictive value], whereas the AUC of the conventional Lewis score was 0.734 (95% CI: 0.589-0.879, p = 0.004). Sensitivity analysis restricted to patients with either complicated (n = 34) or stricturing (n = 26) disease phenotype revealed that midLS still predicted clinical exacerbation during follow-up (AUC 0.747/0.753, respectively), in these patients. MidLS predicts treatment failure in quiescent CD patients (median follow-up of 5 years) independently of disease phenotype.

Analysis of the Association between Fatigue and the Plasma Lipidomic Profile of Inflammatory Bowel Disease Patients.

Inflammatory bowel disease (IBD) is a chronic, relapsing noninfectious inflammatory condition of the intestinal tract with two main phenotypes, ulcerative colitis (UC) and Crohn's disease (CD), and globally increasing incidence and prevalence. Nearly 80% of the IBD patients with active disease and 50% of those with inactive disease suffer fatigue with significant impairment of their quality of life. Fatigue has been associated with multiple factors in IBD patients but, in most cases, no direct cause can be identified, and risk factors in clinically quiescent IBD are contradictory. Furthermore, as the assessment of fatigue is subjective, there is an unmet clinical need for fatigue biomarkers. In this explorative study, we analyzed the plasma lipidomic profiles of 47 quiescent UC and CD patients (23 fatigued, 24 nonfatigued) using ultraperformance liquid chromatography-time-of-flight mass spectrometry (UPLC-TOFMS). The results showed changes in lipids associated with fatigue and IBD. Significantly decreased levels of phosphatidylcholines, plasmanyls, sphingomyelins, lysophosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, phosphatidylserines, and eicosanoids were observed in patients with fatigue. Network and metabolic pathway analysis indicated a dysregulation of the arachidonic acid and glycerophospholipid metabolisms and the sphingolipid pathway. The protein-metabolite interaction network showed interactions between functionally related metabolites and proteins, displaying 40 disease-associated hidden proteins including ABDH4, GLTP, and LCAT.

Within-network brain connectivity in Crohn's disease patients with gadolinium deposition in the cerebellum.

Patients with Crohn's disease (CD) undergo multiple gadolinium-based contrast agent injections across their lifespan to enhance signal intensity of the intestinal wall and differentiate active from quiescent inflammatory disease. Thus, CD patients are prone to gadolinium accumulation in the brain and represent a non-neurological population to explore gadolinium-related brain toxicity. Possible effects are expected to be greater on the cerebellar network due to the high propensity of the dentate nucleus to accumulate gadolinium. Herein, we provide a whole-brain network analysis of resting-state fMRI dynamics in long-term quiescent CD patients with normal renal function and MRI evidence of gadolinium deposition in the brain. Fifteen patients with CD and 16 healthy age- and gender-matched controls were enrolled in this study. Relevant resting-state networks (RSNs) were identified using independent component analysis (ICA) from functional magnetic resonance imaging data. An unpaired two-sample t test (with age and sex as nuisance variables) was used to investigate between different RSNs. Clusters were determined by using threshold-free cluster enhancement and a family-wise error corrected cluster significance threshold of p < 0.05. Patients showed significantly decreased resting-state functional connectivity (p < 0.05, FWE corrected) of several regions of the right frontoparietal (FPR) and the dorsal attention (DAN) RSNs. No differences between the two groups were found in the functional connectivity maps of all the other RSNs, including the cerebellar network. Our findings suggest a non-significant impact of gadolinium deposition on within-network cerebellar functional connectivity of long-term quiescent CD patients.

Diffusion-weighted imaging in quiescent Crohn's disease: correlation with inflammatory biomarkers and video capsule endoscopy

To investigate the role of restricted diffusion in quiescent Crohn's disease (CD) patients and its association with inflammatory biomarkers and endoscopic disease. Fifty-two quiescent CD patients prospectively underwent magnetic resonance enterography (MRE) and video capsule endoscopy (VCE) and were tested for the inflammatory biomarkers, faecal calprotectin (FCP) and C-reactive protein (CRP). Restricted diffusion in the distal ileum was qualitatively (absence/presence) and quantitatively (apparent diffusion coefficient [ADC]) assessed by two readers. The VCE-based Lewis score was calculated for the distal ileum. Restricted diffusion sensitivity and specificity for VCE ulcerations were assessed for patients with elevated (>100 μg/g) or normal (<100 μg/g) FCP. Receiver operating characteristic (ROC) curve was used to assess the ability of ADC to identify patients with concurrent VCE ulceration and elevated FCP. The sensitivity and specificity of restricted diffusion for patients with VCE ulceration were higher in patients with elevated FCP (reader 1: 71.4%, 80%, reader 2: 76.2%, 100%, respectively) compared to patients with normal FCP (reader 1: 46.2%, 61.5%; reader 2: 15.4%, 76.9%, respectively). The ADC had a high diagnostic accuracy for identifying patients that had concurrent VCE ulceration and elevated FCP (reader 1: AUC=0.819, reader 2: AUC=0.832). In quiescent CD patients, the presence of restricted diffusion is suggestive of an active inflammation, associated with elevated FCP. Thus, DWI may serve as a clinical tool in the follow-up of these patients, implying subclinical inflammatory flares.

Cerebral magnetic resonance imaging in quiescent Crohn's disease patients with fatigue.

AIMTo evaluate brain involvement in quiescent Crohn’s disease (CD) patients with fatigue using quantitative magnetic resonance imaging (MRI).METHODSMultiple MRI techniques were used to assess cerebral changes in 20 quiescent CD patients with fatigue (defined with at least 6 points out of an 11-point numeric rating scale compared with 17 healthy age and gender matched controls without fatigue. Furthermore, mental status was assessed by cognitive functioning, based on the neuropsychological inventory including the different domains global cognitive functioning, memory and executive functioning and in addition mood and quality of life scores. Cognitive functioning and mood status were correlated with MRI findings in the both study groups.RESULTSReduced glutamate + glutamine (Glx = Glu + Gln) concentrations (P = 0.02) and ratios to total creatine (P = 0.02) were found in CD patients compared with controls. Significant increased Cerebral Blood Flow (P = 0.05) was found in CD patients (53.08 ± 6.14 mL/100 g/min) compared with controls (47.60 ± 8.62 mL/100 g/min). CD patients encountered significantly more depressive symptoms (P < 0.001). Cognitive functioning scores related to memory (P = 0.007) and executive functioning (P = 0.02) were lower in CD patients and both scores showed correlation with depression and anxiety. No correlation was found subcortical volumes between CD patients and controls in the T1-weighted analysis. In addition, no correlation was found between mental status and MRI findings.CONCLUSIONThis work shows evidence for perfusion, neurochemical and mental differences in the brain of CD patients with fatigue compared with healthy controls.

Brain responses to uncertainty about upcoming rectal discomfort in quiescent Crohn's disease - a fMRI study.

Patients with Crohn's disease (CD) in remission are exposed to chronic psychological distress, due to the constant risk of relapse. This permanent situation of anticipation and uncertainty can lead to anxiety, which may, in turn, trigger relapse. We aimed to investigate the effects of uncertainty on behavioral and brain responses to anticipation of visceral discomfort in quiescent CD patients. Barostat-controlled rectal distensions were preceded by cued uncertain or certain anticipation in nine CD patients and nine matched healthy volunteers. Brain responses obtained before distension across the different anticipation conditions in regions of interest (ROI) involved in (anticipation of) pain were measured using functional magnetic resonance imaging and compared between CD and controls. The association between anxiety-related psychological variables and cerebral anticipatory activity was tested. During uncertainty, CD patients had significantly stronger activations than controls in the cingulate cortex, insula, amygdala, and thalamus with trends in the hippocampus, prefrontal, and secondary somatosensory cortex. In patients, brain responses to uncertainty in the majority of ROI correlated positively with gastrointestinal symptom-specific anxiety, trait-anxiety, and intolerance of uncertainty. In a context of uncertainty regarding occurrence of uncomfortable visceral sensations, CD is associated with excessive reactivity in brain regions known to be involved in sensory, cognitive and emotional aspects of pain processing and modulation, and threat appraisal. Our findings contribute to a better understanding of the role of emotional and cognitive processes in CD. This may, in turn, lead to the development of new (psycho)therapeutic approaches for management of symptoms and related anxiety.

Activation of the prostaglandin D2 metabolic pathway in Crohn's disease: involvement of the enteric nervous system.

BackgroundRecent works provide evidence of the importance of the prostaglandin D2 (PGD2) metabolic pathway in inflammatory bowel diseases. We investigated the expression of PGD2 metabolic pathway actors in Crohn’s disease (CD) and the ability of the enteric nervous system (ENS) to produce PGD2 in inflammatory conditions.MethodsExpression of key actors involved in the PGD2 metabolic pathway and its receptors was analyzed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in colonic mucosal biopsies of patients from three groups: controls, quiescent and active CD patients. To determine the ability of the ENS to secrete PGD2 in proinflammatory conditions, Lipocalin-type prostaglandin D synthase (L-PGDS) expression by neurons and glial cells was analyzed by immunostaining. PGD2 levels were determined in a medium of primary culture of ENS and neuro-glial coculture model treated by lipopolysaccharide (LPS).ResultsIn patients with active CD, inflamed colonic mucosa showed significantly higher COX2 and L-PGDS mRNA expression, and significantly higher PGD2 levels than healthy colonic mucosa. On the contrary, peroxysome proliferator-activated receptor Gamma (PPARG) expression was reduced in inflamed colonic mucosa of CD patients with active disease. Immunostaining showed that L-PGDS was expressed in the neurons of human myenteric and submucosal plexi. A rat ENS primary culture model confirmed this expression. PGD2 levels were significantly increased on primary culture of ENS treated with LPS. This production was abolished by AT-56, a specific competitive L-PGDS inhibitor. The neuro-glial coculture model revealed that each component of the ENS, ECG and neurons, could contribute to PGD2 production.ConclusionsOur results highlight the activation of the PGD2 metabolic pathway in Crohn’s disease. This study supports the hypothesis that in Crohn’s disease, enteric neurons and glial cells form a functional unit reacting to inflammation by producing PGD2.

The link between negative affect, vagal tone, and visceral sensitivity in quiescent Crohn's disease.

Autonomic dysfunction and mood disorders are frequently described in Crohn's disease (CD) and are known to influence visceral sensitivity. We addressed the link between vagal tone, negative affect, and visceral sensitivity in CD patients without concomitant features of irritable bowel syndrome (IBS). Rectal distensions to a discomfort threshold of 70% and onset of pain were performed in nine CD patients in remission and eight healthy controls. Autonomic parameters were evaluated with heart rate variability and electrodermal reactivity. We showed that CD patients had (i) higher scores of depressive symptomatology (12±3 in patients vs 4±1 in controls on the Center for Epidemiologic Studies-Depression Scale; p=0.038), (ii) reduced vagal tone (HF 257±84ms(2) vs 1607±1032ms(2) , p=0.043; LF 455±153ms(2) vs 1629±585ms(2) , p=0.047), (iii) decreased sympathetic reactivity during an aversive stimulus, and (iv) higher tolerance to rectal distension pressures (43±3mmHg vs 30±2mmHg, p=0.002) and low sensitivity index scores. In conclusion, our results provide preliminary evidence that patients with quiescent CD, in the absence of IBS, are hyposensate to experimental rectal distension. These data provide further evidence that anxiety and depressive symptomatology in addition to autonomic dysfunction modulate visceral pain perception in quiescent CD patients in the absence of IBS.

A prospective evaluation of the predictive value of faecal calprotectin in quiescent Crohn's disease

BackgroundFaecal calprotectin (FC) is a non-invasive marker of gastrointestinal inflammation. AimTo determine whether higher FC levels in individuals with quiescent Crohn's disease are associated with clinical relapse over the ensuing 12months. MethodsA single centre prospective study was undertaken in Crohn's disease patients in clinical remission. The receiver operating characteristic (ROC) curve for the primary endpoint of clinical relapse by 12months, based on FC at baseline, was calculated. Kaplan–Meier curves of time to relapse were based on the resulting optimal FC cutoff for predicting relapse. ResultsOf 97 patients recruited, 92 were either followed up for 12months without relapsing, or reached the primary endpoint within that period. Of these, 10 (11%) relapsed by 12months. Median FC was lower for non-relapsers, 96μg/g (IQR 39–237), than for relapsers, 414μg/g (IQR 259–590), (p=0.005). The area under the ROC curve to predict relapse using FC was 77.4%. An optimal cutoff FC value of 240μg/g to predict relapse had sensitivity of 80.0% and specificity of 74.4%. Negative predictive value was 96.8% and positive predictive value was 27.6%, FC≥240μg/g was associated with likelihood of relapse by 12-months 12.18 (95%CI 2.55–58.2) times higher than lower values (p=0.002). ConclusionsIn this prospective dataset, FC is a useful tool to help identify quiescent Crohn's disease patients at a low risk of relapse over the ensuing 12months. FC of 240μg/g was the optimal cutoff in this cohort.

A prospective single‐centre evaluation of the intra‐individual variability of faecal calprotectin in quiescent Crohn's disease

As a non-invasive marker of gastrointestinal inflammation, faecal calprotectin (FC) is being increasingly used to guide the management of Crohn's disease. It is therefore a concern that studies have shown variability in day to day levels. To determine the degree of this intrapersonal variability in the context of quiescent Crohn's disease. A single-centre prospective study was undertaken in 143 Crohn's disease patients in clinical remission. Three faecal calprotectin levels were analysed from stool samples on consecutive days. Consistency of faecal calprotectin levels was determined by measuring the intraclass correlation (ICC). Due to higher variability at higher faecal calprotectin levels, the ICC was calculated for the log-transformed values. The reliability of detecting a 'case' of active inflammation as defined for specific concentrations of faecal calprotectin was measured by the kappa statistic. Ninety-eight complete sets of results were obtained. The ICC was 0.84 (95% CI: 0.79-0.89), which represents low variability across samples. The kappa statistic for the reliability of detecting a case as defined by an FC level of >50 μg/g was substantial at 0.648 (0.511-0.769). Day to day variability of faecal calprotectin is low in our cohort of quiescent Crohn's disease patients and the reliability of defining a 'case' is moderately good. These data provide reassurance to clinicians using a single calprotectin sample to inform therapeutic strategies in this cohort.

PTU-106 A prospective single centre evaluation of the intra-individual variability of faecal calprotectin in quiescent Crohn's disease patients

IntroductionFaecal calprotectin (FC) has become an established non-invasive, sensitive marker of intestinal inflammation in Crohn's disease (CD). A single measurement of FC is used in clinical practice to aid decision...

Bone cells from patients with quiescent Crohn's disease show a reduced growth potential and an impeded maturation

Patients with Crohn's disease (CD) are at increased risk of developing osteoporosis. The mechanism underlying bone loss in CD patients is only partly understood. Inflammation is thought to contribute by causing a disturbed bone remodeling. In this study, we aimed to compare functional characteristics of osteoblasts from CD patients and controls, as osteoblasts are one of the effector cells in bone remodeling. The study included 18 patients with quiescent CD and 18 healthy controls. Bone cells obtained from iliac crest biopsies were cultured in the absence and presence of the inflammatory cytokines IL-1α, IL-1β, IL-6, TNF-α, IL-10, and TGF-β. At various time points, cell proliferation and differentiation were analyzed. Bone cells from CD patients showed a prolonged culture period to reach confluence and a decreased cell number at confluence. CD patient-derived bone cell cultures produced higher alkaline phosphatase levels, whereas osteocalcin levels were considerably reduced compared to control cultures. At the proliferation level, the responsiveness to inflammatory cytokines was similar in bone cells from CD patients and controls. At the differentiation level, CD cultures showed an increased responsiveness to IL-6 and a decreased responsiveness to TGF-β. Responsiveness to the other cytokines tested was unaffected. In summary, we show a reduced growth potential and impeded maturation of bone cells from quiescent CD patients in vitro. These disease-related alterations combined with an unchanged sensitivity of CD patient-derived bone cells to inflammatory cytokines, provide a new insight in the understanding of CD-associated bone loss.

Mo1690 A Prospective Single Centre Evaluation of the Intra-Individual Variability of Faecal Calprotectin in Quiescent Crohn's Disease Patients

Introduction Faecal calprotectin (FC) has become an established non-invasive, sensitive marker of intestinal inflammation in Crohn9s disease (CD). A single measurement of FC is used in clinical practice to aid decision making in the management of CD patients. Data on the day to day variation of FC levels in CD patients is sparse. If there was significant intra-individual variation of FC within CD patients, this could impact on the interpretation of single values in isolation. A prospective study to evaluate the degree of variability of FC in three consecutive days stool samples in CD patients in clinical remission was performed. Methods 143 patients with CD in remission (CDAI Results Of the 143 patients recruited 34 did not return any samples, 6 returned less than the required number of stool samples, 2 withdrew consent and 2 developed clinical evidence of a flare of disease during the collection period and were excluded from analysis. Therefore 98 complete sets of three stool samples were obtained and analysed. The intraclass correlation coefficient of the 3 FC values, log-transformed, was 0.842 with corresponding 95% CI 0.788 to 0.886 showing that consistency between the three log-transformed FC measurements is high. The reliability of a “normal” FC result of Conclusion The consistency of three faecal calprotectin samples over three consecutive days is high and the CI is narrow suggesting that in a larger population consistency would also be high. This indicates that there is little intra-individual variability of the test and a one off sample can indeed provide reliable information for use in clinical practice. Higher intrapatient variability of high FC values suggests that the log-transformed values are more reliable. Competing interests None declared.

Safety and efficacy of extractible self-expandable metal stents in the treatment of Crohnʼs disease intestinal strictures: A prospective pilot study

Endoscopic management of Crohn's disease (CD) intestinal strictures with balloon dilation is effective; however, recurrences are frequent and require further dilations or surgery. The use of extractible metallic stents may be as effective as balloon dilation with fewer recurrences. The aim was to investigate in a prospective pilot study the feasibility and clinical effectiveness of the use of extractible stents in the treatment of CD intestinal strictures. In two tertiary referral centers, quiescent CD patients except for obstructive symptoms associated with intestinal stenosis of less than 50 mm length on enterography were eligible for transitory stent placement, initially planned to be retrieved after 8 weeks, which was secondarily reduced to 4 weeks after patient 3. Eleven patients (six males, five females, median age 34 years [range 18-66]) were prospectively included. The sites of intestinal stenosis were an ileocolonic anastomosis, an ileosigmoidic anastomosis, and the surgically untreated terminal ileum in eight, one, and two patients, respectively. Stent placement was technically successful in 10 patients. Obstructive symptoms were relieved in 6 out of 10 patients. Two patients needed surgery related to the procedure. Six downstream migrations were observed. Only one patient could have the stent extracted as scheduled on day 28 and remains symptom-free after 73 months of follow-up. Even if stenting appears an effective technique in treating symptomatic CD intestinal strictures, the procedure is associated with a prohibitively high rate of spontaneous migrations and complications.

Fecal calprotectin is a predictive marker of relapse in Crohn's disease involving the colon: a prospective study

Fecal calprotectin seems to have a diagnostic precision in predicting relapse in quiescent ulcerative colitis patients. However, the data remain controversial in Crohn's disease. The aim of this study was to prospectively evaluate the role of fecal calprotectin as a predictive marker for 1-year follow-up in patients with asymptomatic Crohn's disease. Fifty-three Crohn's disease patients in clinical remission were consecutively included providing at the beginning of the study a single stool sample as well as a blood sample and regularly followed-up for 12 months. Fecal calprotectin level was measured using a commercially available enzyme-linked immunoassay. Among 53 patients, 10 (18.9%) developed clinical relapse during the 12-month follow-up period. Median fecal calprotectin level was significantly higher in relapse group patients compared with that in nonrelapse group (380.5 vs. 155 microg/g, P<0.001). With a cutoff value of 340 microg/g fecal calprotectin gave sensitivity of 80% and specificity of 90.7% in predicting clinical relapse. Fecal calprotectin level greater that 340 microg/g gave an 18-fold higher risk to develop relapse (log rank P<0.001) and was found to be an independent predictive factor of relapse (P=0.02). Fecal calprotectin seems to be a reliable marker of relapse in quiescent Crohn's disease patients.

Impact of functional bowel symptoms on quality of life and fatigue in quiescent Crohn disease and irritable bowel syndrome

Patients with irritable bowel syndrome (IBS) and Crohn disease (CD) have impaired quality of life (Qol) associated with fatigue. Whether IBS-like symptoms have a similar impact on Qol and fatigue in quiescent CD than in IBS is currently unknown. Our aims were (i) to evaluate the prevalence of IBS-like symptoms in quiescent CD and (ii) to compare the impact of IBS-like symptoms on Qol and fatigue in both diseases. A total of 92 quiescent CD, 40 IBS and 20 healthy subjects similar in age were included prospectively in five French academic centers. IBS symptoms were evaluated through the Rome III criteria. The severity of IBS symptoms, Qol, fatigue, depression and anxiety was measured using questionnaires (Francis Score, Likert scales, Fatigue Impact Scale, short-form Beck and Hospital Anxiety and Depression Scale). Irritable bowel syndrome-like symptoms were found in 42/92 (45.6%) patients with quiescent CD. The presence of IBS-like symptoms was associated with significant more profound alterations of Qol, high scores of fatigue, depression, but similar levels of anxiety. Compared to CD patients with IBS-like symptoms, IBS patients had more severe gastrointestinal symptoms and alterations of Qol, but similar scores of fatigue, depression and anxiety. In quiescent CD patients, fatigue was independently associated with the presence of IBS-like symptoms (OR = 1.018, 95% CI: 1.002-1.034, P = 0.02). The prevalence of IBS-like symptoms is elevated in quiescent CD. The presence of IBS-like symptoms in quiescent CD is probably associated with the range of fatigue/depression disorders. The mechanism underlying the occurrence of IBS-like symptoms in quiescent CD needs to be further explored.