bluuebunny/crossref_metadata_2025 huggingface dataset:
P071 Crohn’s Disease is associated with elevated levels of the pro-inflammatory CXCR3 ligands (CXCL9, 10 and 11) with an associated reduction in Paneth cell derived antimicrobial peptides in ex-vivo ileal biopsies
Authors: Jones F , Doherty G , McNamee E
Published: May 2021

Background

Despite an expanding array of treatment options, a significant proportion of patients with Crohn’s Disease (CD) fail to respond to currently available therapies, underpinning the importance of biological insights into disease pathogenesis. The pro-inflammatory chemokines CXCL9,10 and 11 bind to the CXCR3 receptor, highly expressed on effector T-cells. Mouse models of chronic ileitis have shown that CXCR3+ effector T cells drive the loss of paneth cells that play an important role in innate immunity and mucosal barrier function. In the TNFΔΔARE mouse ileitis-model, small molecule inhibition of the CXCR3 receptor reverses paneth cell loss and restores antimicrobial peptide levels. The aims of this study were to evaluate the role of chemokines that bind to CXCR3+ effector T-cells in adult patients with ileal CD compared to healthy controls and to assess the impact of these pro-inflammatory chemokines on paneth cell derived anti-microbial peptides.

Methods, 13 CD patients and 16 healthy controls attending for routine endoscopic evaluation were prospectively recruited at St.Vincent’s University Hospital, Dublin and ileal biopsies were collected in media. RNA was isolated from homogenised ileal biopsies (Quiagen kit), DNAse treated using DNAse I (Invitrogen) and reverse transcribed using M-MLV reverse transcriptase (Promega). Target cDNAs were quantified using an Applied BiosystemsTM QuantStudioTM 7 Flex Real-Time PCR System.

Results

We identified an increase in the relative mRNA expression of CXCR3 associated chemokines, with significantly higher levels of CXCL9, CXCL10 and CXCL11 in ileal CD patients compared to healthy controls. This coincides with a reduction in paneth cell-derived antimicrobial peptides with significantly lower levels of alpha defensins (DEFA5, DEFA6) and lysozyme in CD patients compared to healthy controls.

Conclusion

This study supports data from animal models and provides a hypothesis for the loss of paneth cells in patients with ileal CD. The reduction in paneth cell derived anti-microbial peptides may help to explain the altered microbiome and provide an explanation for the loss of mucosal barrier integrity in Inflammatory Bowel Disease (IBD). A greater understanding of the role of chemokines in the development of mucosal immunity and inflammation in IBD may allow the targeting of chemokines in novel therapeutic strategies.
P075 Multidimensional assessment of interoceptive abilities, emotion processing and the role of early life stress in Inflammatory Bowel Disease
Authors: Atanasova K , Lotter T , Reindl W , Lis S
Published: May 2021

Background

Perception of internal bodily sensations includes three dissociable processes: interoceptive accuracy, interoceptive sensibility, and interoceptive awareness. Interoception plays a crucial role in emotional processing and alterations of these processes have been already observed in gastrointestinal disorders. Although impairments in interoception may contribute to the burden of disease in IBD, no study has investigated interoceptive processing in IBD as a multidimensional concept. The aim of the current study was to investigate the associations between the different dimensions of interoception and emotional processing in IBD, while taking childhood traumatization into account.

Methods

We recruited 35 remitted IBD patients and 35 healthy control participants (HC) matched for age, sex and education. Interoception was assessed as a multidimensional construct using the Heartbeat tracking task and the Multidimensional Assessment of Interoceptive Awareness questionnaire. Emotional processing was measured using an experimental task, where participants were asked to rate the valence and arousal when presented with affective visual stimuli. Childhood traumatization was assessed using the Childhood Trauma Questionnaire.

Results

IBD patients reported greater awareness of the connection between bodily sensations and emotional states and showed a stronger tendency to use distraction from unpleasant sensations compared with HC. Our findings suggest that emotional processing in IBD is related to interoceptive sensibility and not to the objective interoceptive accuracy. The association between interoception and emotional processing was modulated by the severity of childhood traumatization in both groups.

Conclusion

This is the first study showing that IBD patients did not differ in their ability to detect visceral signals but in their subjective perception of these. Psychotherapeutic interventions in IBD might profit from taking the interplay between emotion processing, interoception and childhood trauma into account.
P110 Symptomology and most bothersome symptoms among pediatric Crohn’s disease and ulcerative colitis patients: Results from a physician and patient survey
Authors: Dotson J , Hunter T , Lukanova R , Crandall W , Komocsar W , Larkin A , Meakin S , Otley A
Published: May 2021

Background

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic gastrointestinal diseases, which often present during one’s most productive years. The objective of this study was to assess the symptomology and most bothersome symptoms of pediatric CD and UC patients.

Methods

Data from a cross-sectional survey of physicians and their pediatric CD and UC patients (age 2–17 years) conducted in France, Germany, Italy, Spain, United Kingdom, Japan, and United States were analyzed. Data were collected in 2019–2020 via physician-completed patient record forms and patient-self completed forms. Patients age 12–17 years completed their own questionnaires, while caregivers of younger children completed their respective questionnaires. Patient demographics and current symptoms were reported by physicians, while the most bothersome symptoms were reported by the patient/caregiver. All descriptive analyses were conducted for CD and UC patients separately.

Results

Data from 1,213 CD patients and 1,162 UC patients were included in this analysis. CD patients had a mean age of 12.8 years, 59.5% were male, 75.5% were Caucasian and had a mean sPCDAI score of 10.7. Similarly, UC patients had a mean age of 12.9 years, 54.0% were male, 71.0% were Caucasian, and had a mean PUCAI score of 23.7. The majority of CD (94.9%) and UC patients (94.6%) were currently enrolled in school/education; however, 68.3% of CD and 61.1% of UC patients indicated that they have missed school/education because of their IBD symptoms. Abdominal pain was the most frequently reported symptoms among CD (41.9%) and UC (38.6%) patients. CD and UC patients reported abdominal pain, diarrhea, abdominal cramps, and bowel urgency as their most bothersome symptoms.

Conclusion

Pediatric CD and UC patients experience multiple symptoms with the most bothersome symptoms being related to abdominal pain and bowel movements. These symptoms may impact pediatric CD and UC patients’ daily lives and cause them to miss school.
P127 Assessing the vaccination and immunization status in a Paediatric Inflammatory Bowel Disease diagnosis
Authors: Palomino Pérez L M , Velasco Rodríguez-Belvis M , León Falconi J L , Sánchez Fernández-Bravo C , Vazquez Gómez J A , Muñoz Codoceo R A
Published: May 2021

Background

Paediatric inflammatory bowel disease (PIBD) patients are especially prone to vaccine-preventable diseases and opportunistic infections. The aim was to evaluate the immunization and vaccination status in PIBD.

Methods

Descriptive and retrospective study that analyzes the immunization and/or vaccination for measles, mumps and rubella (MMR), hepatitis B virus (HBV), chickenpox, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) of PIBD patients in a tertiary paediatric hospital (Jan 2015- Oct 2019) in the first 6 months after diagnosis.

Results

Amongst 57 patients, 17 (30%) had ulcerative colitis (UC), 35 (61%) Crohn ́s disease (CD) and 5 (9%) unclassified IBD (uIBD). Up to 35 (61%) were male and the mean age at diagnosis was 10.2±4.1 years. A total of 18 (32%) were currently on biological treatment and 45 (79%) on immunosuppressants. The disease location in CD patients was L3 (Paris classification) in 22 (63%) and L4a in 13 (37%). Only 2 (6%) showed perianal involvement. From the UC patients, 11 (65%) were E4. A delayed growth was observed in 6 (10%), all CD patients. At diagnosis, 37 (65%) were HBV-vaccinated, 13 of them (35%) had a serological response and 22 (59%) had no response. 18 were re-vaccinated and 9 (50%) had a documented serological response. Up to 34 patients (60%) were MMR-vaccinated and 13 (38%) showed a complete response. Only 6 patients could be re-vaccinated. Up to 30 (52%) showed chickenpox immunization. Only 4 of the non-immunized patients could be vaccinated and all of them responded to a single dose. Regarding CMV and EBV, 17 and 16 patients (46 and 43%) were IgG positive respectively, all of them IgM negative. Patients with CD were more likely to need HBV re-vaccination than other IBDs (p< 0.05). Regarding chickenpox, CD patients without growth delay (G0) needed less re-vaccination than those whose growth was affected (G1) (p< 0.05). However, UC patients with extensive disease (E4) needed less re-vaccination than those with limited disease (p< 0.05). Male patients seemed to be less likely to need re-vaccination, with no significant differences.

Conclusion

The serological assessment of vaccine-preventable diseases immunization yielded poor results. A high percentage of HBV and MMR vaccinated patients showed no response. CD patients tended to more likely need revaccination, especially in the most severe cases (G1). Surprisingly, severity was not related with vaccination response in UC. Our results suggest that less than half of the patients had been previously infected by CMV or EBV. It seems reasonable to serologically check the immunization status in PIBD patients in order to, when appropriate, re-vaccinate before starting immunosuppressive therapies.
P147 Progression to biologic treatment in very early onset inflammatory bowel disease patients- a long term follow up retrospective study
Authors: Eindor A , Meleady L , Jacobson K
Published: May 2021

Background

Very early onset inflammatory bowel disease (VEOIBD) prevalence has been increasing over the last decades. These young patients have been known to have special disease characteristics and disease location. Although it is known that only a low percentage of these patients require biologic treatment after diagnosis, there is only scarce evidence about their long- term outcome and biologic requirements. We aimed to assess the long term outcome of VEOIBD patients and the time of progression to biologic treatment.

Methods

We retrospectively reviewed IBD patients diagnosed under 6 years of age, between January 2005 and December 2019, from the British Columbia (BC) Pediatric IBD database. Demographic data, disease characteristics and symptoms at diagnosis were documented. The disease location and severity were documented according to the Paris classification. Data collected retrospectively until the last appointment recorded in the electronic medical records included whether the patient received biologic treatment at the time of follow up, the time to intiation of the treatment, the type of biologic treatment and response. Kaplan meier curves were used to asses the number of years to progression to biologic treatment and the parameters influencing it.

Results

89 patients under the age of 6 were diagnosed with IBD during the study period. 3 patients failed to meet inclusion criteria and were excluded. Median age at diagnosis was 3.8 (IQR 2.6–5.1). 45.3% of patients had Crohn’s disease (CD) and 62.8% were males. Median time of follow up was 6.39 (IQR 3.71–10.55). 68.1% of the ulcerative colitis (UC) patients had pancolitis and 48.7% of CD patients had ileocolonic disease. 39.5% of patients were started on biologic treatment and 7.1% underwent surgery. Kaplan Meier curves demonstrated that patients diagnosed in the years 2012 -2019 had shorter duration of progression to biologics than those diagnosed 2005–2011 (p=0.0047). In patients with CD those with perianal or stricturing disease progressed faster to biologic treatment (p=0.024,p=0.038, respectively) and in UC patients those with high severity of disease (p=0.017). 63.6% of patients were reported to be on clinical remission on the biologic treatment.

Conclusion

Although VEOIBD patients have more extensive diseas, they require less biologic treatment than previously reported in older patients. Factors influencing shorter duration of progression to biologics were the severity of disease and behaviour and not disease location. Patients diagnosed more recently had shorter duration to biologic treatment which might reflect physicians perception on using biologic treatment in these young patients rather than disease severity.
P169 Vitamin D levels are inversely associated with inflammation in pediatric InflammatoryBowel Disease patients
Authors: Cenni S , Russo G , De Nigiris A , Casertano M , Pacella D , Miele E , Martinelli M , Staiano A , Strisciuglio C
Published: May 2021

Background

Multiple pathways link Vitamin D status with the risk of development and the clinical course of Inflammatory Bowel Disease (IBD). However, limited studies have been conducted on the relationship between vitamin D and disease activity in IBD, especially in pediatric population and the results have been inconsistent. Moreover Vitamin D metabolites may provide a more precise assessment of sufficiency and mineral metabolism than total 25-hydroxyvitamin-D (25(OH)D). The aim of our study was to evaluate the concentrations of total25(OH)D, 24,25-dihydroxyvitamin D (24,25(OH)2D) and calcitriol (1,25-(OH)2D) to correlate these values with the disease activity markers.

Methods

We prospectively enrolled all IBD pediatric patients. Total 25(OH)D, 24,25(OH)2D and1,25-(OH)2D levels were measured by enzyme-linked immunosorbent assay (ELISA). In each patient with IBD, the activity scores of disease and the main inflammation markers were correlated to Vitamin D metabolites. We prospectively enrolled all IBD pediatric patients. Total 25(OH)D, 24,25(OH)2D and1,25-(OH)2D levels were measured by enzyme-linked immunosorbent assay (ELISA). In each patient with IBD, the activity scores of disease and the main inflammation markers were correlated to Vitamin D metabolites.

Results

One hundred twenty three consecutive IBD children were enrolled, 43% with Crohn Disease (CD),55% Ulcerative colitis (UC), 2% indeterminate colitis. No difference in 25(OH)D,24,25(OH)2D and 1,25-(OH)2D levels were found between CD and UC patients. A significant indirect correlation was found between C reactive protein and 1,25-(OH)2D levels in patients with IBD (r=-0.275, p=0.046) and in CD group (r=-0.477, p=0.039). Moreover, in patients with IBD and CD we found a significant indirect correlation between erythrocyte sedimentation rate(ESR) and 25(OH)D (r=-0.212, p=0.024 and and r=-0.282, p=0.047 respectively). Instead, in the UC group we found only a direct correlation for both fibrinogen and ESR with 1,25-(OH)2Dlevels (r=0.407, p 0.028 and r=0.446, p=0.013).

Conclusion

Our results suggest that both the active form and the total Vitamin D levels are inversely associated with disease activity especially in CD children. Further studies are needed to clarify the role of Vitamin D deficiency as a consequence or a cause of inflammation.
P175 Complete endoscopic healing is associated with lower disability than partial mucosal healing in Crohn’s disease: a prospective multicentric study
Authors: Yzet C , Brazier F , Sebbagh V , Vanelslander P , Dejour V , David B , Nguyen-Khac E , Diouf M , Fumery M
Published: May 2021

Background

Crohn’s disease (CD) has a significant impact on health status and quality of life, by affecting physical and emotional well-being and by impairment of social and functional abilities. In the era of treat to target concept, endoscopic healing has emerged to be the goal to achieve to prevent intestinal damage and disability. It is not clear what level of endoscopic healing is associated with CD disability. We, therefore, aimed to compare disability associated to complete endoscopic healing or partial endoscopic healing in patients with CD.

Methods

We conducted a multicentric prospective study, between September 2019 and November 2020, in one University Hospital, one general hospital and one private practice center including consecutive patients with CD in clinical remission and either complete mucosal healing (CDEIS =0) or partial mucosal healing (CDEIS > 0 and ≤ 4). The 10-item self-questionnaire IBD-disk was used to assess disability. Moderate-to-severe disability was defined as an overall IBD-disk score ≥ 40.

Results

A total of 82 patients were included. Forty-four (53%) were women, the median age and disease duration were respectively 35.3 years (Interquartile range (IQR 28.6–45.2) and 8.0 years (IQR, 3.0–17.0). The median overall IBD-disk score was 26.5 (IQR, 9 -45.0) and 30 (36.6%) had moderate-to-severe disability. Complete endoscopic healing was observed in 48 patients (57.3%). Median IBD-Disk score was respectively 24 (IQR, 9.0–40.5) and 34 (IQR, 9.5–51.5) for patients with complete and partial endoscopic healing (p=0.068). Respectively, 13/48 (27%) and 17/34 (50%) of patients with complete and partial endoscopic healing had moderate-to-severe disability (p=0.039). In multivariate analysis, partial mucosal healing (OR=3.04, CI95% [1.11, 8.94], p=0.03), female gender (OR=3.93, CI95% [1.43, 11.94], p=0.008) and smoking (OR= CI95% 5.88 [1.72, 25.0] p=0.039) were significantly associated with moderate-to-severe disability. Among the IBD-disk subscores, defecation score (median, IQR) (0.0 [0.0–3.0] vs 4.0 [0.0–7.5], p=0.028) and energy score (4.0 [0.0–6.0] vs 6.0 [2.5–8.0], p=0.023) were significantly lower in complete endoscopic healing.

Conclusion

One-third of patient with endoscopic healing reported moderate-to-severe disability. Complete endoscopic healing (CDEIS = 0) was associated with lower disability than partial endoscopic healing (CDEIS > 0 and ≤ 4) in CD. Deeper endoscopic healing may be needed to reduce the risk of disability in CD.
P177 Adherence to a bowel cleansing regimen for pan-enteric capsule endoscopy in patients with suspected Crohn’s disease and factors affecting the image quality
Authors: Jacob Broder B , Karina Winther A , Jensen M D
Published: May 2021

Background

Pan-enteric capsule endoscopy (CE) is an attractive diagnostic approach in patients examined for Crohn’s disease (CD). The current bowel cleansing regimen was developed for patients with suspected gastrointestinal neoplasia (polyps). Since the majority of patients with CD have diarrhoea, a reduced volume of bowel preparation may be sufficient for cleansing the colon. The aim of this study was to examine the adherence to the recommended bowel cleansing regimen in patients with suspected CD examined with pan-enteric CE and determine clinical factors affecting the image quality.

Methods

Patients with clinically suspected CD were prospectively enrolled in a trial examining non-invasive modalities for diagnosing CD (http://ClinicalTrials.gov Identifier NCT03134586). All patients had a standardized work-up including medical history, physical examination, blood and stool samples and pan-enteric CE. CE was performed with the PillCam™ Crohn’s capsule (Medtronic, Dublin, Ireland) after overnight fasting and bowel preparation with 2 + 2 litres of Polyethylene glycol (Moviprep®, PEG + ascorbic acid) and Sodium Phosphate booster as previously described by ESGE. Readers were blinded to the results of other examinations. The image quality was graded on a 4-point scale (poor, fair, good, excellent). A good or excellent image quality defined a diagnostic procedure.

Results

The volume of ingested PEG was recorded in 59 patients (Table 1). The mean volume was 2.5 L (CI 2.3–2.8). 10 patients (17%) were able to drink all 4 L of PEG, and 44 patients (75%) ingested > 2 L. The image quality was poor, fair, good or excellent in 0%, 29.3%, 29.3% and 41.4%, respectively. The mean volume of PEG was 1.9 L (CI 1.4–2.4), 2.2 L (CI 1.8–2.7) and 3.2 L (CI 2.8–3.5) in patients with a fair, good or excellent image quality (P < 0,001, Figure 1). In a regression analysis including multiple clinical variables, only the volume of ingested PEG was associated with the obtained image quality (Spearman’s rho = 0.52; P < 0.001). Stool consistency, number of bowel movements, diagnosis of inflammatory bowel disease (IBD) or the degree of inflammation did not affect the image quality. The diagnostic yield was equal in patients with a diagnostic or non-diagnostic image quality (44% and 44%, respectively). The capsule was excreted in 53 patients (90%), and the analysis was not able to determine factors affecting the completion rate.

Conclusion

In patients examined with pan-enteric CE for suspected CD, the ingested volume of PEG is the major factor affecting the image quality. However, only few patients are able to ingest the recommended volume. Future research should determine the optimal bowel cleansing regimen for patients examined for IBD.
P209 Prevalence and risk factors for fatigue in chronic inflammatory bowel disease
Authors: Hassine A , Hammami A , Braham A , Jaziri H , Jmaa A
Published: May 2021

Background

Fatigue is one of the most common symptoms reported by patients with chronic inflammatory bowel disease (IBD), being in flare or in remission. Thus, several fatigue measurement tools have been developed. The objective of our work was to assess the prevalence of fatigue in patients with IBD and its impact on daily life, and to determine its risk factors.

Methods

This is a cross-sectional study of patients followed for IBD who presented to our consultation during the three months preceding the study. Fatigue assessment was performed by IBD-F score (The Inflammatory Bowel Disease Fatigue Self-assessment Scale). The higher the score, the more disabling the fatigue. The activity of Crohn’s disease (CD) was assessed by the Harvey-Bradshaw index (HBI), that of ulcerative colitis (UC) by the clinical Mayo score.

Results

One hundred patients were included. Thirty-two patients (32%) had UC and 68 patients (68%) had CD. The mean age was 42.18 years [16–81 years], with a predominance of men (sex ratio = 1.5). Severe disease activity was noted in 14 patients (20.6%) with CD and 10 patients (31.3%) with UC. Extra-intestinal manifestations, particularly articular, were noted in 20% of cases. 36% of patients were in clinical remission. The prevalence of fatigue was 94.11% in MC and 93.75% in RCH. Fatigue was noted in 83.3% of patients in remission.Fatigue was severe (section I score between 11 and 20) in 40% of patients. We found a significant association and a linear correlation between the presence and severity of fatigue and CD activity (p <0.001, r = 0.84), as well as UC activity (p <0.001, r = 0.74). A significant association was found with extra-intestinal manifestations (p = 0.028), as well as with the presence of other chronic diseases (p = 0.014). In 30% of cases, fatigue was responsible for a functional handicap (section II score between 61 and 120). This effect was also strongly correlated with disease activity: MC (p <0.001, r = 0.74) and RCH (p <0.001, r = 0.73).

Conclusion

Assessing the severity of fatigue and its impact on the daily activities of patients is a crucial pillar in the management of patients with IBD. In our series, the prevalence of fatigue was 94%. It was associated and correlated with the degree of disease activity.
P211 Pseudopolyps are associated with increased fecal calprotectin levels in patients with Inflammatory Bowel Disease in clinical and endoscopic remission
Authors: Spigarelli De Rábago I , Suárez Ferrer C , Poza Cordón J , Martín Arranz E , Sánchez Azofra M , Rueda García J L , Suarez Cabredo C G , Hernández Pérez M , Martín Arranz M D
Published: May 2021

Background

Fecal calprotectin (FC) has become a fundamental tool in the non-invasive monitorization of activity in patients with inflammatory bowel diseases (IBD). However, there is still debate over the choice of the optimal cut-off point for the different clinical settings. The aim of this study is to analyze whether the presence of pseudopolyps and their characteristics have an impact on the value of FC and should therefore be taken into account when deciding the optimal cutoff values.

Methods

A single-centered, retrospective analysis including data from patients with colonic Crohn′s disease or Ulcerative colitis who underwent colonoscopy for dysplasia screening at our center between 2018 and 2019. Patients that did not have a FC registered within 8 months from to the colonoscopy, or that did not maintain clinical remission between the colonoscopy and the measurement of the FC, were excluded. Patients that had activity in the colonoscopy (Mayo endoscopic score >0, SESCD >0) were also excluded.

Results

73 patients were included. 26 (35.6%) of them had pseudopolyps in the colonoscopy. The median value of the FC was significantly different in patients with pseudopolyps (110.1 µg/g, CI 95% [48.6–171.5]) compared to those without them (52.5 µg/g, CI 95% [29.9–75.1]). In 11 (42.3%) of the patients with pseudopolyps, biopsies were taken, observing histological activity in 3 of them (27.3%) and no inflammatory activity in the other 8 (72.7%). We found that FC was higher in patients with inflammatory polyps (119.0 µg/g) in comparison to those without histological activity in their pseudopolyps (96.9 µg/g); however, these results were not statistically significant. The location of the pseudopolyps had no influence over the FC in our study. In addition, no correlation was found between the presence of polyps or diverticula and FC.

Conclusion

In our study, the presence of pseudopolyps is associated with significantly higher levels of FC. Moreover, our results suggest a tendency towards higher FC in patients who had active colitis in the histological samples of their pseudopolyps.
P233 Sleep Disorders and Chronic Inflammatory Bowel Disease: What’s the Connection?
Authors: Hassine A , Hamami A , Dahmani W , Ben Ameur W , Elleuch N , Braham A , Bannour R , Jaziri H , Jmaa A
Published: May 2021

Background

The quality of sleep is a major determinant of quality of life, which has become a therapeutic target in the management of Chronic Inflammatory Bowel Diseases (IBD). The relationship between IBD and sleep disorders is still unclear. Although poor quality sleep is believed to be strongly linked to disruptions to clinical disease activity, IBD patients are reported to experience sleep disturbance even when the disease is clinically inactive. The objective of this work was to assess the prevalence and risk factors of sleep disorders as well as their impact on the quality of life of patients with IBD.

Methods

We conducted a cross-sectional study, including all patients followed for IBD, who presented to our consultation during the three months preceding our study. The quality of sleep was assessed by the Pittsburgh Sleep Quality Index (PSQI). The quality of sleep is impaired when the PSQI score> 5. The activity of Crohn’s disease (CD) was evaluated by the Harvey-Bradshaw index (HBI), that of ulcerative colitis (UC), by the Clinical Mayo score. Quality of life was assessed by the Short Inflammatory Bowel Disease Questionnaire (S-IBDQ).

Results

We included 100 patients, mean age 42.18 ± 15.71 years with a predominance of men (sex ratio M / F = 1.5). The mean course of IBD was 9.02 ± 6.57 years. Sixty eight patients (68%) had CD, the location was ileal in 32 patients (47%), ileocolonic in 22 patients (32.4%), and colonic in 14 cases (20.6%). Ano-perineal manifestations were present in 38.2% of cases. Severe disease activity was noted in 14 patients (20.6%). Thirty two patients (32%) had UC. Pancolitic involvement was noted in 14 patients (43.7%) UC activity was severe in 10 patients (31.3%). The mean PSQI score was 8.2 ± 4.42. A PSQI score> 5 was noted in 68% of patients. There is a significant association between the PSQI score and disease activity in both patients with CD (p = 0.003) and those with UC (p = 0.026). The quality of sleep was altered in 44.4% of patients in remission vs. 81.25% of patients in relapse, with a statistically significant difference (p <0.001). There was a strong negative correlation between the PSQI score and the S-IBDQ (p <0.001, r = -0.61).

Conclusion

Our study showed that 68% of patients with IBD suffer from impaired quality of sleep. This disturbance was strongly correlated with the deterioration in the quality of life of these patients, requiring multidisciplinary management.
P235 Major Depression in patients with Crohn’s disease and its relationship with clinical activity and disease’s phenotype
Authors: Facanali C , Sousa Freitas Queiroz N , Facanali M R , Rodrigues Boarini L , Amuratti Gonçalves J L , Rodrigues Borba M , Nahas S C , Sobrado C W
Published: May 2021

Background

Crohn’s disease (CD) has a considerable impact on quality of life and contributes to the onset of depressive symptoms¹. It has been demonstrated that depression is more prevalent in inflammatory bowel disease (IBD) patients compared to the general population². However, whether depression affects IBD course or the onset of IBD triggers psychological disorders remains to be elucidated. The aim of the study is to estimate the prevalence of major depression in patients with CD and to evaluate its relationship with the clinical activity and phenotype of the disease.

Methods

From November 2019 to February 2020, 283 patients with CD were evaluated using the Patient Heath Questionnaire-9 (PHQ-9). Major depression (MD) was defined by PHQ-9 ≥ 10 (0–4: absent depressive symptoms / 5–9: mild depressive symptoms / 10–14: moderate depressive symptoms / 14- 27: severe depressive symptoms). Data regarding socio-demographic characteristics, disease phenotype, clinical activity were prospective collected. Disease phenotype was characterized according to the Montreal classification and clinical activity was assessed using the Harvey-Bradshaw index (HBI). Statistical tests were performed with a 5% significance level.

Results

The prevalence of MD in CD patients was 41.7% (Table 1). Female patients were more susceptible to MD (Table 2). Other socio-demographic characteristics did not increase the risk of MD. Disease activity was significantly associated with an increased risk of MD (Odds Ratio [OR] 795.97, 95% confidence interval [CI] 133.7–4738.78, p <0.001) (Table 2). Regarding disease phenotype, the stenosing and penetrating behaviour were associated with a lower risk of MD (OR 0.8, 95%CI 0.01-.5 and OR 0.03, 95%CI 0.00–0.18), respectively, as compared with the inflammatory behaviour. No association was observed between location of the disease and MD.

Conclusion

Our study shows a high prevalence of MD among CD patients, which is significantly affected by disease phenotype and clinical activity. Given that the ultimate therapeutic goals for CD should include restoration of quality of life, this study shed light on the need of the inclusion of psychological assessment besides the objective measures of disease activity as an integral part of IBD care.
P239 A study to evaluate uptake of PROMS for IBD patients on Biologics: a sample United Kingdom district general hospital experience
Authors: Mahmood T , Muhammad Q
Published: May 2021

Background

In order to guide industry on medical product development, FDA developed an instrument to measure effectiveness as an endpoint of clinical trials. This patient oriented tool is called “Patient Related Outcomes Measures”. (PROMS). In 2009 NHS England adopted PROMS declaring that “the purpose is to collect information, from patients themselves, about how well the health service is treating them. Moreover “PROMs allows to understand the difference that healthcare interventions make to people’s quality of life”. Initially related to only certain surgical procedures, it eventually rolled out to many other conditions including IBD. This research looks at degree of success in implementation of PROMS for IBD patients on treatment with biologics in a sample district hospital of United Kingdom.

Methods

The IBD PROMs questionnaire is filled by patients themselves when treated with biologics. The questionnaire asks overall health status, treatment of bowel condition, effectiveness in controlling bowel condition, satisfaction with quality of treatment, Crohn’s and Colitis questionnaire CCQ12 and uses 12 dimensions: sleeping, appetite, energy level, rushing to the toilet, being bloated, incomplete emptying of bowels, blood in stool, generally unwell, faecal incontinence, nocturnal diarrhoea, passing wind and effect on leisure activity. It also has questions for patients with a stoma. We collected data from a sample district general hospital in United Kingdom for one year in retrospect and analysed the implementation of PROMS. We hoped at least 90% of patients would fill the PROMS questionnaire.

Results

45 patients with IBD who were on biologics were recruited in the study. They had repeated admissions for treatment and we kept check points at 3, 6 and 12 month follow up treatments. There were 21 patients on infliximab, 23 on vedolizumab, and 1 on ustekinumab with overall total number of infusions being 352 due to their recurrent admissions for biologic treatment. A minimum of 45 PROM responses could have been achieved and maximum of 352 for good implementation. In our data only 4 were filled (8.89% of minimum and 1.1 of maximum required). Thus PROMS for IBD was not implemented to any useful extent.

Conclusion

Our study did not look at the outcomes, but simply whether the PROMS was utilised sufficiently for IBD patients on biologics. We demonstrated low uptake by one sample district general hospital of United Kingdom. Further studies to evaluate practice of other IBD units in the country would help to understand the situation better. There can be various reasons for this low uptake including lack of resource, not knowing importance of PROMS or deficient motivation in staff.
P315 Population pharmacokinetics and pharmacodynamics of ozanimod in ulcerative colitis
Authors: Tatosian D , Shen J , Chen L , Lavigne J , Teuscher N , Harris S , Chitkara D , Tirucherai G S , Marta C
Published: May 2021

Background

Ozanimod is an oral small molecule sphingosine 1-phosphate receptor modulator approved for relapsing forms of multiple sclerosis (RMS) and under development for ulcerative colitis (UC) and Crohn’s disease. Ozanimod and its major active metabolites CC112273 and CC1084037 block lymphocyte egress from lymphoid tissues, reducing the absolute lymphocyte count (ALC) in blood. To characterise the influence of patient characteristics on ALC response, a population PK/PD analysis was conducted.

Methods

A nonlinear mixed-effects Emax model described the ALC time course and relationship to CC112273 concentrations in healthy subjects and patients with UC or RMS. The analysed data included 34,449 ALC values obtained from 4122 subjects enrolled in 11 Phase 1, 2, and 3 clinical studies. The effect of age, sex, smoking status, disease type, body weight, total bilirubin, and baseline ALC on the maximum ALC reduction (Emax) and half-maximal concentration (EC50) were investigated. Simulations of typical ALC reductions for healthy subjects and patients with UC or RMS receiving 0.5 or 1 mg ozanimod were conducted to explore the influence of smoking and assess the time for ALC recovery.

Results

Increasing CC112273 concentrations were associated with reductions in ALC to a maximum of 74% from baseline, with an estimated EC50 of 2.8 nM CC112273. Healthy subjects, females, and higher body weights were associated with larger ALC Emax (Figure 1), while healthy subjects, increased age, nonsmokers and higher baseline ALC were associated with an increased EC50 (Figure 2). UC patients receiving 0.5 mg and 1 mg ozanimod HCl are predicted to have mean ALC reductions of 46.1% and 57.2%, respectively, with similar reductions for RMS patients of 48.0% and 57.4%. Smoking was associated with a 27.2% reduction in the ALC EC50, which partially offsets the reduced plasma CC112273 concentrations in smokers. Simulations show that 1 mg ozanimod has comparable ALC reductions of 57.4% in nonsmokers and 52.7% in smokers. Upon discontinuing ozanimod 1 mg in UC patients, a mean recovery time to normal (1 x 109/L ALC count) of 32.8 days was predicted, with 90% of the population recovering in 3 months. Overall results were consistent with findings from clinical trials.

Conclusion

Population analysis demonstrated a similar PK/PD relationship for ALC reductions in patients with RMS and UC. Smoking was not associated with substantial difference in ALC, consistent with no loss of efficacy in smokers. Upon discontinuation of ozanimod treatment, the majority of UC and RMS patients will recover lymphocyte counts to normal within 3 months.
P410 Which patients with established Crohn’s disease benefit most from the use of the Patency capsule test prior to small bowel capsule endoscopy?
Authors: Elosua Gonzalez A , Rullan Iriarte M , Rubio Iturria S , Rodríguez Gutiérrez C , Vicuña Arregui M , Elizalde Apesteguía I , Aznárez Barrio M R , Juanmartiñena Fernández J F , Nantes Castillejo Ó , Fernández-Urién I
Published: May 2021

Background

An important factor that limits a wider utilization of small bowel capsule endoscopy (SBCE) in Crohn’s Disease (CD) is the potential risk of retention. The Patency® capsule (PC) lowers the risk of SBCE retention by assessing pre-procedure intestinal patency. Our aims were to evaluate the use of PC in patients with established CD in routine clinical practice and to identify predictive factors of intestinal patency in CD patients.

Methods

We included all patients with CD followed in the Inflammatory Bowel Disease Unit of the Complejo Hospitalario de Navarra in which a SBCE was performed from 01/01/2008 to 31/12/2019. An intact PC excreted in its original shape within 30 hours after swallowing was considered a positive patency test.

Results

A total of 465 SBCE were indicated in 333 patients. In 61.9% a previous patency test with PC was performed, with significant differences in its use according to the age at diagnosis according to the Montreal classification (A1 75.9%, A2 64.8%, A3 46.1%) and behaviour (B2 81.3%, B3 80%, B1 54.2%), the indication (postoperative recurrence monitoring 87.2%, flare 65.5%, staging small bowel disease 52.4%, assessing mucosal healing 44.8%) and the presence of previous CD surgery (68.6% vs. 55.6%). In 33 cases (7%) SBCE was contraindicated due to negative patency test.

Eleven SBCE were retained of the 432 procedures finally performed (incidence 2.5%; 95% CI 1.06%-4.02%). Retention occurred in 5.6% of procedures without prior PC compared to 0.4% with previous PC (p<0.001). Stricturing disease (OR 2.94; 1.31-6.58), penetrating disease (OR 3.85; 1.59-9.31) and presence of elevated inflammatory markers (OR 3.73; 1.85-7.50) were identified as independent factors associated with retention (negative PC test or SBCE retention) in the multivariate analysis.

Conclusion

A patency test prior to SBCE was performed in 61.9% of patients with known CD. The use of PC is associated with a lower risk of SBCE retention in a routine clinical setting. Patients with stricturing or penetrating disease or elevation of inflammatory markers have significantly higher risk of retention and would therefore benefit from a pre-SBCE PC.
P437 Hyperbaric oxygen therapy for Inflammatory Bowel Disease – a systematic review
Authors: Meima - van Praag E , Lansdorp C , Smeekes G , Gecse K , van Hulst R , Buskens C
Published: May 2021

Background

Inflammatory bowel disease (IBD) is a chronic, debilitating disease with suboptimal success rates after conventional treatments. A potential new, additional approach is hyperbaric oxygen therapy (HBOT). We aimed to evaluate the efficacy and safety of HBOT in patients with IBD.

Methods

A systematic review of the published literature regarding HBOT as treatment for IBD was conducted according to the PRISMA guidelines. MEDLINE, Web of Science, EMBASE and the Cochrane Library were systematically searched. Search terms included ‘Hyperbaric Oxygenation’, ‘Inflammatory Bowel Diseases’, ‘Crohn’ and ‘Colitis’. All human studies with ≥5 patients and animal studies evaluating HBOT for IBD were included. Primary outcome was clinical response rate to HBOT. Secondary outcomes were radiological and endoscopic response rate, laboratory findings, adverse events and quality of life (QoL).

Results

The literature search resulted in 948 publications of which 26 were included (Figure 1); 11 human studies (778 patients) and 15 animal studies (554-558 animals). Seventeen were randomised controlled trials, 8 prospective cohort studies and 1 was a retrospective cohort study. The overall clinical response rate after 5-86 HBOT sessions was 82.1% (88.1% for ulcerative colitis and 78.7% for Crohn’s disease (CD)). Perineal CD was described in 56 patients, with a clinical response rate of 75%. The endoscopic response rate ranged from 50-100% in 4 studies and the radiological response in 1 study was 100%. Only one study described quality of life (QoL) and showed no significant differences in QoL between the HBOT and control group. Adverse events were described in 6 studies and occurred in 9 out of 75 patients (0.12%).

Animal studies reported less weight loss after HBOT and a significantly decreased Disease Activity Index compared to controls. Furthermore, histopathological features and laboratory values including inflammatory markers (such as TNF-α and IL-1) and oxidative stress markers (such as myeloperoxidase and malondialdehyde) improved after HBOT.

Conclusion

HBOT is a promising IBD treatment with high clinical-, radiological- and endoscopic response rates and few adverse events. Animal studies support these findings. The challenge now is to identify the appropriate amount of HBOT sessions and timing in the IBD treatment process and to identify which IBD patients can benefit most from HBOT.
P453 The use of immunosuppresants is associated with high treatment persistence rates for infliximab and adalimumab as first or second line anti-TNF therapy in patients with inflammatory bowel disease
Authors: Theodoraki E , Orfanoudaki E , Foteinogiannopoulou K , Drygiannakis I , Koutroubakis I E
Published: May 2021

Background

The aim of this study was to investigate the factors associated with treatment persistence for infliximab and adalimumab, as 1st or 2nd line anti-TNF therapy, in patients with inflammatory bowel disease (IBD).

Methods

A retrospective study of patients with IBD from the registry of our department who received infliximab (IFX) or adalimumab (ADA), during the period of 2002–2019 was performed. The persistence rate of IFX and ADA at 1 and 3 years from treatment initiation as 1st and 2nd line anti-TNF therapy respectively was calculated. In addition, possible related factors were analyzed.

Results

We included 185 patients with IBD, naive to biologics, who initiated with anti-TNF treatment [105 men (57%), mean age (± SD) 44.5 ± 14.7 years, Crohn’s disease 144 (78%), median disease duration (IQR) 13 (7–20) years, 120 (65%) under IFX, 100 (55%) in combination with immunosuppressive therapy for at least 6 months]. In 59 patients [Crohn’s disease 47 (80%)] IFX or ADA was used as 2nd line anti-TNF therapy. The duration of administration and persistence rate of IFX and ADA as 1st and 2nd line treatment are shown in Table 1.

In univariate analysis statistically significant associations between the persistence rates of anti-TNF therapy as first-line therapy, with the use of immunosuppressants (P = 0.04) and treatment intensification (P = 0.01) in both 1st and 3rd year (P = 0.01 and 0.04 respectively) were found. No other significant association between demographic, disease type and clinical parameters and treatment persistence was found. Regarding the 2nd line anti-TNF treatment, persistence of therapy in the 1st year was associated with treatment intensification (P = 0.02) and in the 3rd year of administration with the combination with immunosuppressants (P = 0.05). In multivariate analysis only the use of immunosuppresants remained statistically significant associated both in 1st and 3rd year of treatment in 1st line therapy (P=0.05 and P=0.003 respectively). This was also the case in 2nd line therapy but only in the 3rd year of treatment (P=0.05).

Conclusion

The persistence rates of IFX and ADA used both as a 1st and 2nd line therapy in IBD patients are significantly associated with the combined use of immunosuppressants.
P456 Ig glycosylation in ulcerative colitis: it’s time for new biomarkers
Authors: Capecchi R , Migliorini P , Zanzi F , Maltinti S , Puxeddu I , De Bortoli N , Bellini M , Costa F , Marchi S , Bertani L
Published: May 2021

Background

Ulcerative colitis (UC) is a chronic relapsing disease, which needs a continue monitoring, especially during biological therapies. An increasing number of patients is treated with anti-Tumor Necrosis factor (TNF) drugs, and current research is focalized to identify biomarkers able to monitor the disease and to predict therapeutic outcome.

Methods

We enrolled consecutive UC patients treated with anti-TNF, naïve to biologic drugs. Therapeutic outcome was evaluated after 54 weeks of treatment in terms of clinical remission (Partial Mayo Score -PMS- <2) and mucosal healing (Mayo Endoscopic Score <2). On serum samples collected at baseline and after 54 weeks of treatment, a Lectin-based ELISA assay was performed, and specific glycosylation patterns were evaluated by biotin-labelled lectins. We have also collected 21 healthy controls (NHS) samples, age and sex-matched.

Results

Out of 44 UC patients enrolled, 22 achieved clinical remission and mucosal healing after 54 weeks. At baseline, when Protein A was used as coating, UC patients non-responders showed a reduced reactivity to Jacalin (JAC) in comparison with NHS (p=0,04). After one year of treatment, a decrease in JAC binding was seen only in responders, in comparison with baseline (p=0,04). When JAC binding was tested selecting IgG by means of Fab anti-IgG Fab, UC patients displayed an increased reactivity after anti-TNF therapy (p<0,0001 vs controls). At baseline, PMS inversely correlates with JAC binding when Fab anti-IgG Fab was used in solid phase (r2= 0,2211; p=0,0033). Patients with higher PMS at baseline (PMS ≥5) presented lower binding capacity for JAC in comparison with NHS and with lower PMS patients (p= 0,0135 and p=0,0089 , respectively).

Conclusion

Ig glycosylation was correlated with clinical and endoscopic activity in patients with UC. JAC protein A-selected Ig showed a possible role in predicting therapeutic effectiveness. If these data would be confirmed, Ig glycosylation could be used as biomarker in UC.