bluuebunny/crossref_metadata_2025 huggingface dataset:
P460 Biomarkers reflecting extracellular matrix turnover and inflammation can be used to monitor disease activity and treatment response in patients with Crohn’s disease undergoing infliximab induction therapy
Authors: Sorokina Alexdóttir M , Bourgonje A R , Asser Karsdal M , Bay-Jensen A C , Faber K N , Loveikyte R , van Dullemen H M , Visschedijk M C , Festen E A M , Weersma R K , Dijkstra G , Mortensen J H
Published: May 2021

Background

Crohn’s disease (CD) is a relapsing-remitting inflammatory disease of the gastrointestinal (GI) tract characterized by high protease activity and increased extracellular matrix (ECM) turnover. Although immunotherapeutic drugs such as anti-TNFα have shown great promise in the treatment of CD, still up to 20–40% of patients do not respond to therapy. Failure to establish effective treatment may lead to further disease progression and potential disease complications. The aim of this study was to investigate whether biomarkers of ECM turnover and intestinal inflammation could serve as non-invasive tools for monitoring treatment response to anti-TNFα in patients with CD.

Methods

Serum biomarkers of matrix metalloproteinase (MMP)-related type I collagen degradation (reC1M), intestinal inflammation (VICM [macrophage activity], CPa9-HNE [serum calprotectin, neutrophil activity]) and type III collagen formation (PRO-C3) were measured using competitive ELISA in patients with CD (n=54) undergoing infliximab (IFX) induction therapy. Disease activity was defined by composite assessment of the Harvey-Bradshaw Index (HBI) together with physician’s global assessments (PGA). Clinical remission (HBI <5) was assessed at week 14. Wilcoxon signed-rank tests were applied for pairwise comparisons of biomarker levels between baseline and week 14.

Table 1. Differences in biomarker levels between baseline and week 14 in CD patients receiving IFX treatment stratified by response. Biomarker concentrations presented as median [IQR].

Results

In patients responding to IFX treatment (n=50), serum levels of reC1M, VICM, and CPa9-HNE (all P<0.05) were significantly lower at week 14 compared to baseline. However, serum levels of PRO-C3 (P<0.01) were significantly elevated in responders at week 14 compared to baseline. No significant changes were observed in the biomarkers between baseline and week 14 in those not responding to IFX treatment (n=4).

Conclusion

Serum biomarkers for type I collagen degradation (reC1M), intestinal inflammation (VICM, CPa9-HNE) and type III collagen formation (PRO-C3) are linked to the pathology of CD, reflecting treatment response. Together, these biomarkers could be used as surrogate markers for disease monitoring during IFX treatment in CD to further improve disease management.
P461 Vedolizumab Dose Escalation in a Real-World Cohort of IBD Patients
Authors: Zelinkova Z , Kadleckova B , Lucenicova J
Published: May 2021

Background

Vedolizumab (VDZ) effectively induces and maintains remission in inflammatory bowel disease (IBD). The loss of response to VDZ has been shown to be recaptured with dose escalation but the data in this field are still scarce. In addition, data on pharmacokinetics (PK) of dose escalation are limited and it is unclear whether PK should used in decision-making algorithm in adjusting VDZ dose regimen. Therefore, the aim of our study was to assess clinical efficacy and pharmacokinetic profile of VDZ dose escalation.

Methods

All IBD patients treated with VDZ in one tertiary IBD centre were retrospectively retrieved from the database. According to local protocol, non-responders to standard dosing of 300 mg i.v. of VDZ every 8 weeks, received escalated dose of 300mg i.v. every 6 or 4 weeks. Disease activity was assessed by Harvey-Bradshaw index (HBI) and partial Mayo score in Crohn’s disease (CD) and ulcerative colitis (UC) pts; respectively. VDZ dose was escalated in case of clinically assessed primary non response by week 22 of the treatment or in case of secondary loss of response. Response to dose escalation was defined as a decrease of HBI of ≥2 points, partial Mayo score ≥3 points or endoscopic improvement. VDZ through levels were assessed at the completion of induction and in dose escalated patients after at least two VDZ administrations in shortened interval.

Results

In total, 75 IBD patients were included (mean age 47 years, range 20–90; 36 men; 35 CD/39UC/1 IBD-U). Fifty two pts (69%) were primary responders, out of these 23 pts (44%) required dose escalation at some point of the treatment due to secondary loss of response. Out of 23 primary non-responders, 10 stopped the treatment, the remaining 13 received escalated dose of VDZ.

Altogether, dose escalation was used in 36 pts (48%). There were no differences in the proportion of CD and UC between conventional and escalated dose regimen groups. Among secondary loss of response, the response was recaptured in 15 out of 23 pts (65%} while only two out of thirteen primary non-responders responded to dose escalation.

There were no significant differences in VDZ levels between pts requiring dose escalation and pts with stable response to conventional regimen (mean levels 9,97±1,276 vs. 12,79±1,771 µg/mL; p=n.s.). VDZ levels increased significantly in patients who responded to dose escalation (from 10,12±3,460 to 20,81±3,326 µg/mL; p=0.0497).

Conclusion

Response to vedolizumab can be successfully recaptured in two thirds of secondary non responders by dose escalation. Patients requiring dose escalation do not seem to differ from stable responders with regards to vedolizumab pharmacokinetics.
P481 Effectiveness and safety profile of biological therapy in inflammatory bowel disease: real life data from an active pharmacovigilance project
Authors: Viola A , Barbieri M A , Pisana V , Cutroneo P M , Fries W , Spina E
Published: May 2021

Background

Biological therapies are now the mainstay for the treatment of Inﬂammatory bowel disease (IBD). Post-marketing activities become crucial for monitoring the long-term safety. Aim of this project was to evaluate the eﬀectiveness and the safety proﬁle of biologics for the treatment of IBD patients during a prospective pharmacovigilance study.

Methods

From January 2017 to December 2020, all patients with Crohn’s Disease (CD) and Ulcerative Colitis (UC) treated with at least one biologic agent at the start of the study or commenced a biologic during the study period were enrolled. Demographic, clinical, and disease-related data were collected. A descriptive analysis of patients’ characteristics at the index date was performed. Moreover, an analysis of all adverse events (AEs) and all primary/secondary failures expressed as number of AEs or failures/10 treatment years was carried out taking into account the total years of treatment for each biologic including all patients treated with a biologic at least once during the follow-up period.

Results

A total of 654 patients were enrolled, 58.4% with CD and 41.6% with UC. Mean age (±SD) was 44 ± 17 years and 59.0% were males. At the index date, the following treatments were used: 40.8% adalimumab (ADA), 33.3% inﬂiximab (IFX), 21.3% vedolizumab (VED), 2.4% ustekinumab (UST), and 2.1% golimumab (GOL). Patients naïve for biologic therapy were 79.1%. The total years of treatment were 887 yrs for ADA, 663 yrs for IFX, 309 yrs for VED, 89 yrs for UST, and 51 yrs for GOL. Data for AEs and failures were the following: IFX – 1.1 AEs and 0.8 failures, ADA – 0.8 and 0.9, VED – 1.1 and 1.8, GOL – 1.2 and 3.4, and UST - 1.4 and 0.9, respectively (Tab.1). During follow-up, 196 AEs were reported. Infections mainly occurred in patients treated with GOL and ADA (8.7% and 7.6%, respectively), skin reactions in patients treated with ADA (7.6%), while infusion related reactions with IFX (12.6%). A higher frequency of malignancies was observed in patients on treatment with VED (3.4%).

Conclusion

There were no major differences for AEs between the different treatments, but a higher frequency of failures with GOL and VED, both rarely used as first line therapies. Nevertheless, the acquisition of data from clinical practice should be endorsed to better define the safety and efficacy profile of new biologic agents in IBD.
P487 The feasibility of a digital platform for improving disease management among patients with Ulcerative Colitis
Authors: Oddsson S , Gunnarsdottir T , Ylanne K , Molander P , Thorgeirsson T
Published: May 2021

Background

Ulcerative colitis is an idiopathic inflammatory condition of the colon and is the most common form of inflammatory bowel disease worldwide. It is a systemic disorder with no cure and therefore needs lifelong monitoring and management. This study’s objective was to assess the feasibility and preliminary effectiveness of using a digital therapeutic intervention to improve disease management among patients with ulcerative colitis.

Methods

Nine patients were recruited by the Finnish Crohn’s and Colitis Patient Association to participate in a 4-week intervention via a digital platform (Sidekick Health). The primary outcomes included patient ratings of the platform and its therapeutic effects and patient reports of quality of life, physical activity, and medication adherence (on a scale from 0–10). Questionnaires were administered before and after the intervention. The study was conducted during the spring of 2019.

Results

All nine participants completed the intervention (age-range=25–45, eight females and one male). Although not statistically significant, on average, all measures showed improvements from pre to post-intervention: quality of life improved for 7/9 participants (an average improvement of 10.3%), physical activity increased for 6/9 participants (an average of 3.3% increase). Also, medication adherence improved among 6/9 participants (improvement by 6.4% on average), supported by platform data indicating that 8/9 participants had used the platform medication reminders. In 86% of the daily reminders, they were acted upon and rewarded within the platform. Post-program, patients reported their experience of the program and when asked if they would recommend the program to others, the average score was 8.67 out of 10 possible. Also, 8/9 participants agreed or strongly agreed with the statement that the program had changed their health for the better.

Conclusion

This small feasibility study suggests a digital therapeutic intervention is feasible and possibly an effective way to improve disease management among patients with ulcerative colitis. A more extensive study of this intervention is warranted.
P499 Use of an Inflammatory Bowel Disease illustrated guide as a patient education tool
Authors: Murray J , Lindsay J
Published: May 2021

Background

Inflammatory bowel disease (IBD) is a lifelong condition with a major impact on QOL. Patient education and empowerment are cornerstones of high quality IBD patient care 1 and IBD clinical nurse specialists (CNS) play a key role in patient education within IBD. Multiple barriers to effective patient education exist and tools which overcome these are required. We explored IBD CNS’s opinion on (i) the barriers to effective education of patients, (ii) tools they use to overcome these barriers and (iii) the effectiveness of the use of an IBD illustrated guide.

Methods

We studied a guide developed by PostScript Medical™. An illustrative guide to Inflammatory Bowel Disease contained 20 anatomical illustrations related to IBD and its management (Figure 1). The guide and participation in the study were advertised online via UK IBD nursing networks and sent out to those who registered interest. Participants were encouraged to use the guide as frequently as possible in patient consultations. 8 weeks later an electronic survey was sent to all those who received the guide.

Figure 1. IBD multi-disciplinary team (MDT) members were involved in guide development, it can be personalised during each consultation using the attached dry wipe pen

Results

68 UK IBD CNS registered interest in the study and were sent a guide, 47 follow-up survey responses were received (response rate 69%). The top 3 reported barriers to effective patient education were complex terminology (81.63%), time limitations (81.63%) and existing patient knowledge (69.39%). The most frequent tools used to overcome these included patient information leaflets (63.27%), own drawings or sketches (57.14%) and print outs from websites (57.14%). 100% of respondents felt easily accessible visual support tools would help overcome some of these challenges. Responses on the effectiveness of the guide are shown in table 1 and 2. 100% of respondents would use the guide again in future consultations.

Table 1. Responses on effectiveness of guide during patient consultations

Table 2. IBD CNS perception on how guide may affect patient outcomes

Conclusion

This study identified key barriers to IBD CNS based patient education and common tools used to overcome them. It demonstrated the perceived benefit on patient understanding and engagement of using the PostScript Medical™ guide during patient consultations. This should be further explored by analysing patients’ perspective along with other members of the IBD MDT as we seek to explore tools that enhance IBD patient understanding and improve the personalised care we deliver to our patients.

Reference

1. Kapasi R. et al. Consensus standards of healthcare for adults and children with IBD in the UK. Frontline Gastroenterology 2020;11:178–187.
P523 Survey to identify patient characteristics, treatment preferences and impact of inflammatory bowel disease (IBD) on quality of life across 7 countries in Europe
Authors: Fiorino G , Bent-Ennakhil N , Varriale P , Braegger F , Hoefkens E
Published: May 2021

Background

The treatment paradigm for inflammatory bowel disease (IBD) is becoming increasingly diverse and complex. It is suggested that engaging patients through shared decision-making optimises treatment selection in line with clinical need and patient preference and expectations. This patient survey aimed to explore patients’ preferences towards attributes of currently available advanced therapies for IBD as well as the impact of IBD on patients’ quality of life (QoL) across 7 countries in Europe. The demographic profile of the study cohort and findings on the patient-rated impact of IBD on QoL are reported here.

Methods

An online, cross-sectional survey (October 2020 to January 2021) enrolling adults aged ≥18 years who self-reported having and being previously/currently treated for Crohn’s disease (CD) or ulcerative colitis (UC) was conducted across Europe (France, the UK, Spain, Italy, Belgium, Switzerland and the Netherlands). Patient perspectives on IBD care and preferences regarding specific attributes of existing treatment options were explored using the Carenity platform and via partnerships with local organisations. This descriptive analysis evaluated the demographic and clinical profile of respondents, treatment management and impact on QoL.

Results

Overall, 686 patients (CD: 360; UC: 326) across 7 countries completed the survey. Among CD and UC patients, respectively, 71.9% and 57.7% were females; mean age (range) was 48.0 (19.0–77.0) and 50.0 (19.0–82.0) years; and mean disease duration (range) was 13.6 (0.2–49.1) and 11.0 (0.1–68.7) years. Overall, 37.5% of CD patients reported fistulising CD, and 9.4% (CD) and 10.1% (UC) of patients had a stoma or pouch; 76.7% (CD) and 78.5% (UC) of patients were being treated for IBD. Approximately 50.0% of patients with IBD were full-time or part-time employed at the time of survey. Abdominal pain, fatigue, and stool frequency were ranked by 83%, 79%, and 73% patients with CD, respectively, as the symptoms most impacting QoL; 79%, 71%, and 61% patients ranked energy status, general well-being and daily activities, respectively, as the most impacted aspects. Abdominal pain, stool frequency and fatigue were ranked by 73%, 72% and 67% patients with UC, respectively, as the symptoms most impacting QoL; the most impacted aspects were similar to those of patients with CD. Patients in both groups prioritised general well-being, energy status and daily activities as aspects for improvement through treatment.

Conclusion

This large European survey highlights the most impactful symptoms and QoL aspects from the patient perspective. These findings can support clinical decision-making and treatment strategies to improve treatment outcomes and patient QoL.
P561 Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Mayo Endoscopic Score (MES) in predicting the therapeutic effect of mesalazine in UC patients
Authors: Wu L , Zhang Y , Cao Q
Published: May 2021

Background

The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and the Mayo Endoscopic Score (MES) were developed as an objective method of the endoscopic severity in ulcerative colitis (UC); however, it was still unclear whether UCEIS and MES could guide the mesalazine treatment in UC.

Methods

Consecutive UC patients who had undergone colonoscopy within 1 month before starting mesalazine between October 2011 and July 2016 were retrospectively evaluated. Demographic data, previous therapy, clinical observations, laboratory parameters, medical therapy and endoscopic assessments were documented. The primary outcome was the need for ‘step up’ treatment (containing the use of corticosteroids, immunomodulatory or surgery.) during admission and follow-up.

Results

Sixty-five patients were enrolled, 12(18.5%) needed ‘step up’ treatment’ due to primary or secondary nonresponse to mesalazine. UCEIS score is a predictor of primary or secondary nonresponse to mesalazine in multivariate analysis (OR, 25.65; 95% CI, 3.048–45.985; P =0.003). Receiver-operator characteristic (ROC) area of UCEIS is 0.95, with a sensitivity of 100% and specificity of 84.6%, using cut-off value of 6, which outperforms MES with the ROC area of 0.70; When UCEIS score ≥6, 60% of patients eventually need ‘step up’ treatment.

Conclusion

UCEIS score is a useful instrument for evaluating endoscopic improvement in UC patients treated with mesalazine. The high probability of mesalazine treatment failure and benefits of other therapy should be discussed in patients with baseline UCEIS ≥ 6.
P567 Pharmacist-managed immunomodulator clinic in titration and monitoring of immunosuppressants in Inflammatory Bowel Disease
Authors: Ng V , Lim T G , Ong W C , Wong S Y A , Salazar E , Chan P W W
Published: May 2021

Background

Immunomodulators (IMs) such as azathioprine are the cornerstone in the treatment of inflammatory bowel disease (IBD). However, they are associated with significant toxicity and requires close monitoring for side effects, which puts a stretch on our physician clinics. The pharmacist-run Immuno Clinic (IMC) was set up in 2016 to assist in the monitoring of stable patients and initial titration phase of IMs so that physicians are able to focus their time and energy on patients with more complex diseases. The objective of this study is to demonstrate that IMC is able to effectively and safely carry out its purpose for patient’s disease management, medication adherence and adverse events management, resulting in time and cost savings.

Methods

This is a retrospective study looking at IBD patients who attended IMC from Aug 2016 to July 2019. Patients’ demographics, disease control, medication adherence and adverse effects were obtained from the IMC database. Descriptive data were analyzed using frequency distribution for categorical variables. Continuous variables were expressed as median and interquartile range (IQR).

Results

A total of 73 patients were included. Thirty-six (49.3%) patients had CD, while 37 (50.7%) patients had UC. A total of 185 actions were executed over 173 IMC sessions, including dose adjustment (57), recommending additional medications (14), discontinuation or restarting IM (12), side effects detection (25), monitoring recommendations (10), non-adherence detection (39), referral to physician (23), and others (5). In 2 out of 173 visits (1.1%), severe disease flare requiring hospitalization was detected and referred back to the primary physician for inpatient admission. Thirty ADRs were detected (17.3 %) and managed promptly. There were 24 cases of non-adherence detected and counselled (13.9%). Out of 38 patients who were referred for titration of IM, 28 patients (73.7%) achieved the target dose of IM. Patient visits were largely independently managed by pharmacists (150 out of 173, 86.7%).

Conclusion

Implementation of pharmacist-led IMC is a safe and cost-effective alternative to conventional gastroenterology clinic for monitoring and titration of IMs, enabling physicians to focus on more complicated cases and thus improving access to the IBD ambulatory care service.
P578 Adriatic-Balkan regional survey on COVID-19 in Inflammatory Bowel Disease patients
Authors: Borzan V , Orsic Fric V , Borzan B
Published: May 2021

Background

COVID-19 pandemic completely changed the world during the past year, but its’ greatest impact was on healthcare system. As inflammatory bowel diseases (IBD) are chronic conditions, and patients are in constant interaction with healthcare system and are treated with immunosuppressive therapies, they present a particularly vulnerable group of patients during the pandemic.

Methods

Aim of this study was to survey IBD patients’ opinion on the impact of COVID-19 on their mental health, availability and quality of healthcare and their opinion on vaccination. We created a questionnaire that was posted to web based IBD patient group that gather patients from our geographical, Adriatic-Balkan, region (Croatia, Bosnia and Hercegovina, Serbia, Macedonia and Montenegro). Patients answered questions anonymously. Answers were created as yes/no, in grades from 1 (no impact/fear) to 5 (very large impact/very severe fear) or by choosing one of the offered answers. In total, 167 responses were received between December 2020 and March 2021, and were analyzed by descriptive statistics.

Results

A total of 167 IBD patients filled the questionnaire, of which 116 (69,5%) were female. Median age was 36 years (min. 15, max. 62 ys). Most patients did not have COVID-19 (82,6%). A little over half of patients believe that IBD patients are at higher risk of developing COVID-19 (n=97, 58,1%). COVID-19 pandemic has a moderate to large impact on their mental health in majority of patients (n=106, 63,5%) and 99 patients (59,3%) feel moderate to severe fear for their own health because of the pandemic. Most of the information about COVID-19 patients found on the internet (44,3%), from patients’ associations (26,3%) and from their IBD doctor (22,8%). Same number of patients (n=48, 28,7%) feel no impact or very large impact of pandemic on availability to IBD team. Most of patients did not change their IBD therapy during the pandemic (86,8%), and majority (62,3%) felt there was no impact of pandemic on the availability to their therapy. Almost half of patients (49,7%) feel that the quality of healthcare system is worse since the beginning of the pandemic. More than half of patients (57,5%) do not want to be vaccinated against COVID-19.

Conclusion

COVID-19 pandemic had a moderate to large impact on mental health in majority of patients. It is particularly important that patients receive correct information about COVID-19 from medical professionals, and patients’ association groups are very useful channel for patient education that should be used more. More than half of patients do not want to be vaccinated, showing the importance of patient education even more.
P581 Pre-operative prolonged antibiotic treatment in ileocecal Crohn’s disease: single center non-randomized prospective study
Authors: Vardanyan A , Ovsyannikova V , Peda E , Nanaeva B , Achkasov S
Published: May 2021

Background

Patients with complicated Crohn’s disease are the most difficult cohort to make right decision in treatment and timing surgery. These patients are at risk for the long duration of operations, length of hospital stay, repeated urgent interventions because of complications and the need for a temporary stoma. In literature there is lack of information concerning the usage of prolonged antibiotics in such cases and results are conflicting in some studies. Single center non-randomized prospective study was held.

Methods

120 patients were evaluated from 2012 to 2017. All patients had a complicated Crohn’s disease with abdominal mass, fistulas and stricture of the terminal ileum and all of them were operated on. In the first group there were 48 patients who received preoperative treatment with ciprofloxacin and metronidazole for at least 2.5 (1–4) months. In the second group patients also received the same treatment for the median time of 13 (1–33) days. Our hypothesis has been that prolonged treatment allows to reduce postoperative complications and the risk of stoma formation. To prove this statement, we did Chi-squared and Fisher’s exact test, univariant and multivariant analyses. The following criteria were included: prolonged treatment, gender, age, perianal lesion, laparoscopic operation, blood loss and duration of surgery.

Results

In the first group the complication rate was 4 (8.3%) and in 27 (56.2%) patients there was the need for stoma formation. In the second group – 18 (25%) and 58 (80.5%), respectively. First, we used Fisher’s test to see some correlations between the treatment and complications and the need of stoma formation. Prolonged treatment reduces the rate of complications in 4-fold (OR 0.25; x2= 5.34; p=0.02) and the need of stoma in 3-fold (OR 0.3; x2=8.24; p=0.004). In uni- and multivariant analyses prolonged treatment significantly reduces the complication rate and the risk for stoma creation (OR 2.73 CI 0.037–0.86; p= 0.02 and OR 0.310 CI 0.02–0.72 p=0.004, respectively). Gender, age, perianal lesion, laparoscopic operation, blood loss and duration of surgery were not statistically significant in multivariant analysis.

Conclusion

preoperative prolonged antibiotic treatment in complicated Crohn’s disease significantly reduced complications rate and the risk of stoma creation.
P584 Mucosal Eosinophilia is an Independent Predictor of Vedolizumab Effectiveness in Ulcerative Colitis
Authors: Gremida A , Huang K , Ciorba M , Deyali C , Deepak P
Published: May 2021

Background

Ulcerative Colitis (UC) is characterized by intestinal inflammation with chronic inflammatory features. Along with the typical neutrophil-predominant inflammation, there has been growing understanding of the role of eosinophils in UC and the potential therapeutic benefit of Vedolizumab (VDZ) in those cases. VDZ blocks gastrointestinal homing of T lymphocytes and eosinophil recruitment to the intestinal mucosa via blocking α4β7 which plays a major role in eosinophils localization to the intestinal mucosa. We aimed to assess whether mucosal eosinophilia can predict response to VDZ.

Methods

A retrospective study in a single IBD center. Active UC patients who were initiated on VDZ were identified. All patients had at least one documented encounter of VDZ infusion, colonoscopy prior to initiation of VDZ and afterwards with mucosal biopsies at both time points. The endoscopic activity was scored using Mayo endoscopic subscore (MES) with remission as MES 0 or 1. Clinical response was assessed using Physician’s Global Assessment (PGA) as no response, partial or complete clinical response and clinical remission. Histology was reported by an expert GI pathologist and the response was assessed as none, partial or complete. Mucosal eosinophilia was graded at initial and follow-up biopsies as not conspicuous vs. conspicuous with predominance of eosinophils (>100 eosinophils in at least 2 hpf). Eosinophil activity defined as presence of at least 1 of the 3 histologic features: eosinophilic microabscesses, eosinophilic cryptitis, or degranulated eosinophils

Results

107 UC patients were included in the study with a mean age of 44.9 years, majority were males (N = 61, 55.5%), Caucasians (N = 96, 87.3%) and with pancolonic location (N = 100, 90.9%). Mean disease duration was 11.3 yrs (SD, 8.6). 55.5% of patients had prior aTNF exposure. Clinical remission was observed in (N = 63, 57.3%) and endoscopic remission (N = 73, 66.4%) after initiating VDZ. Complete histological response was observed in (N=50, 46.7%). Baseline characteristics based on endoscopic remission is shown where male sex, disease location and the proportion of patients with conspicuous eosinophils with abnormal activity in mucosal biopsies as well as no improvement in eosinophil activity compared to pre-treatment biopsies is greater among those not in endoscopic remission. In a stepwise backward logistic regression model including sex and disease location, improvement in abnormal eosinophilic activity was independently associated with increased odds of endoscopic remission after initiating vedolizumab (OR 4.3; CI, 1.1 - 16.4, p = 0.03).

Conclusion

In ulcerative colitis, change in mucosal eosinophilia after initiating VDZ was an independent predictor of endoscopic remission with VDZ.
P593 Ustekinumab for the treatment of perianal Crohn’s disease. A real-world experience in a Spanish hospital
Authors: Algara San Nicolas M , Masedo Gonzalez A , Gomez Gomez G J , Yela San Bernardino C , Casis Herce B , Martinez Montiel M P
Published: May 2021

Background

Perianal Crohn’s disease (pCD) is difficult to treat. Although anti-TNF, are the medical mainstay in fistula treatment, many patients become refractory. Recent data suggested that ustekinumab (UST) might be effective in pCD.

This study aims to assess the effectiveness of UST in refractory pCD in the real-world practice.

Methods

This is a retrospective cohort of patients with pCD treated with UST in our IBD Unit between march 2015 and october 2020. We analyze demographics, disease charactersistics, surgical for pCD and prior exposure including inmunomodulators and biologic agents. The success of UST was defined on the physician judgment (improvement or absence of drainage). In patients with inactive pCD we analyzed rate of relapse. To analyze predictive factors of treatment success we performed a univariate and multivariable analysis.

Results

Fifty three patients were included (54.72 % female). Twenty four of them were smokers. The median age was 54 years (45–62). The mean duration of CD was 19 years and 50.94% had an intestinal resection. Fifty one patients (96,22%) had been treated with at least 1 anti-TNF and 38 (71.7%) with at least 2 anti-TNF. Sixteen had failed to vedolizumab.

The median follow-up was 26 months (15–36). Twenty two (22/53) had active pCD. Eleven (50%) had intensified UST out of technical sheet (8 with 90 mg sc every 4 to 6 w, and 3 had 130 mg iv every 4 w). Fifteen patients (68.18 %; p<0.001) had clinical improvement after started UST, 10/22 (45.45%; p <0.001) radiological improvement and no one of them require other treatment (p < 0.006). In multivariable analysis, no factors were associated with clinical or radiological improvement.

Two of 32 patients (6.45%) with inactive pCD relapsed during the follow-up.

Eleven patients (20.75%) discontinued UST: 6/53 (11.3%) due to adverse events (infections and arthralgia), 4/53 (7,54) patient′s choice or physician judment. One patient who had been treated with four biologics before UST developed a pleomorphic cutaneous sarcoma

Conclusion

Ustekinumab might by an effective treatment in refractory pCD. More studies are needed to confirm our data
P640 Characteristics of elderly onset Inflammatory Bowel Disease in a cohort of Hispanics
Authors: Ramos L , Anca M , Feliciano K , Amaya C , Perez A , Torres E A
Published: May 2021

Background

The incidence and prevalence of elderly-onset Inflammatory Bowel Disease (EO-IBD), defined as diagnosed >60 y/o, is increasing. The natural history of this cohort is unclear. Disease behavior in elderly patients may differ between adult onset IBD (AO-IBD) and EO-IBD. Comorbidities, age-related frailty and side effects of medications are challenges. We compare a cohort of Hispanic EO-IBD and elderly AO-IBD patients in the IBD Registry, a database collecting demographic and medical data of patients since 1995.

Methods

Of 1345 subjects,122 were ≥60 y/o at recruitment, including AO and EO subjects. Variables included age at diagnosis, gender, IBD type, family history of ulcerative colitis (UC) and Crohn’s disease (CD), disease extent, extraintestinal manifestations (EIM), surgery, and medications. Descriptive statistics were calculated for interval and ratio variables. Frequencies and percentages were calculated for nominal variables cross-tabulated by age of diagnosis. The study is approved by the IRB.

Results

Of the 122 subjects, 59 (48.4%) had AO-IBD and 63 (51.6%) EO-IBD. Mean age of diagnosis was 49.6 y/o for the AO group and 66.4 y/o for the EO group, disease duration was 15.37 yr for AO and 3.73 yr for EO (P<.001). Female gender was more frequent (52.5%: AO, 55.6%: EO-IBD). Most were non-smokers (AO: 57.6%, EO:54%). UC was more common (AO: 62.7%, EO: 60.3%). Family history of CD was low (AO: 6.8%, EO: 6.4%), while family history of UC was more frequent in AO-IBD (18.6% vs 12.7 % in EO-IBD). Small bowel CD was the most frequent (48%) in both groups. UC extension was most commonly pancolitis (AO:58%, EO: 41%. Corticosteroid and biologic use were higher in AO-IBD (see table). EIMs were reported by 41% of AO and 27% of EO, the most frequent was joint involvement (17% AO and 16% EO). Cancer was reported in 3.4% of AO-IBD and 1.6% of EO-IBD. Osteoporosis was reported on 14% of AO-IBD and only 2% in EO-IBD. Surgery was more frequent in the AO group, 41% (n = 24) vs 24% (n = 15) in EO.

Conclusion

Baseline characteristics, disease location and behavior were similar in AO and EO IBD groups. Use of corticosteroids, biologics and surgery were less frequent in the EO-IBD group (not significant). Whether these findings are related to a shorter disease duration, less severe disease or a more conservative management dictated by age and co-morbidities needs to be explored. Selecting the appropriate treatment option for elderly individuals is an important clinical issue.
P685 Gut microbiota in patients with Inflammatory Bowel Disease during remission
Authors: Pisani A , Rausch P , Ellul S , Bang C , Tabone T , Marantidis Cordina C , Zahra G , Ellul P , Franke A
Published: May 2021

Background

Dysbiosis in patients with active IBD has been described in many studies and populations. There is, however, minimal data on whether dysbiosis persists during remission and the extent to which it does. The aim of this study was to assess the gut microbiota in Maltese IBD patients who are in remission as compared to a healthy control population.

Methods

Stool samples of patients with IBD in remission and healthy controls were analyzed by 16S rRNA sequencing. High quality Amplicon sequence variants (ASV) were derived and classified via DADA2.

Results

Ninety-eight patients with IBD (UC: 67.3%; CD: 32.7%) and 97 controls were recruited. Patients with IBD had a decrease in alpha diversity compared to healthy controls (Figure 1) with significant differences in beta diversity (Bray-Curtis dissimilarity, Jaccard distance and Generalized UniFrac distance: all p=0.0001). At the phylum level, abundances differed significantly with respect to health condition (Figure 2). Twenty-five ASVs that were differentially abundant between the different cohorts were identified (Table 1); 13 being over abundant in healthy individuals, while 6 being least abundant among controls. In both CD and UC, 3 different ASVs were found to be more abundant.

Conclusion

Despite remission, the faecal gut microbiota in IBD is dysbiotic. Future studies could be directed at assessing whether species identified as being more abundant in controls can be used as probiotics to either reduce or be able to stop the standard medications.
The Political Economy of Preferential Trade Agreements: An Empirical Investigation
Authors: Facchini Giovanni , Silva Peri , Willmann Gerald
Published: May 2021

We develop a political economy model to study the decision of representative democracies to join a preferential trading agreement, distinguishing between free trade areas and customs unions. Our theoretical analysis shows that bilateral trade imbalances and income inequality are important factors determining the formation of preferential trading agreements, whereas the patterns of geographic specialisation explain whether a customs union or a free trade area will emerge. Our empirical analysis—using a comprehensive panel dataset spanning 187 countries over the period 1960–2015—provides strong support for these predictions.
Copy number evolution in simple and complex tandem repeats across the C57BL/6 and C57BL/10 inbred mouse lines
Authors: Flynn Jullien M , Brown Emily J , Clark Andrew G
Published: May 2021

Simple sequence tandem repeats are among the most rapidly evolving compartments of the genome. Some repeat expansions are associated with mammalian disease or meiotic segregation distortion, yet the rates of copy number change across generations are not well known. Here, we use 14 distinct sublineages of the C57BL/6 and C57BL/10 inbred mouse strains, which have been evolving independently over about 300 generations, to estimate the rates of copy number changes in genome-wide tandem repeats. Rates of change varied across repeats and across lines. Notably, CAG, whose expansions in coding regions are associated with many neurological and genetic disorders, was highly stable in copy number, likely indicating stabilizing selection. Rates of change were positively correlated with copy number, but the direction and magnitude of changes varied across lines. Some mouse lines experienced consistent losses or gains across most simple repeats, but this did not correlate with copy number changes in complex repeats. Rates of copy number change were similar between simple repeats and the more abundant complex repeats after normalization by copy number. Finally, the Y-specific centromeric repeat had a fourfold higher rate of change than the homologous centromeric repeat on other chromosomes. Structural differences in satellite complexity, or restriction to the Y chromosome and elevated mutation rates of the male germline, may explain the higher rate of change. Overall, our work underscores the mutational fluidity of long tandem arrays of repeats, and the correlations and constraints between genome-wide tandem repeats, which suggest that turnover is not a completely neutral process.
Metachronal Motion across Scales: Current Challenges and Future Directions
Authors: Byron Margaret L , Murphy David W , Katija Kakani , Hoover Alexander P , Daniels Joost , Garayev Kuvvat , Takagi Daisuke , Kanso Eva , Gemmell Bradford J , Ruszczyk Melissa , Santhanakrishnan Arvind
Published: May 2021

Synopsis

Metachronal motion is used across a wide range of organisms for a diverse set of functions. However, despite its ubiquity, analysis of this behavior has been difficult to generalize across systems. Here we provide an overview of known commonalities and differences between systems that use metachrony to generate fluid flow. We also discuss strategies for standardizing terminology and defining future investigative directions that are analogous to other established subfields of biomechanics. Finally, we outline key challenges that are common to many metachronal systems, opportunities that have arisen due to the advent of new technology (both experimental and computational), and next steps for community development and collaboration across the nascent network of metachronal researchers.
Queen Pregnancy Increases Group Estradiol Levels in Cooperatively Breeding Naked Mole-Rats
Authors: Edwards Phoebe D , Arguelles Daphne A , Mastromonaco Gabriela F , Holmes Melissa M
Published: May 2021

Synopsis

For cooperative species, there can be great value in the synchronization of physiological states to coordinate group behavioral states. This is evident in naked mole-rats (Heterocephalus glaber), which have the most extreme form of cooperative breeding in mammals. Colonies have a single reproductive female, “the queen,” and 1–3 breeding males. These breeders are supported by adult “subordinates,” which are all socially suppressed into a pre-pubertal state. Subordinates cooperate in colony maintenance, defense, and alloparental care. Prior work has reported that there may be social sharing of hormones among individuals in the colony because when the queen is pregnant, subordinates of both sexes develop enlarged nipples and female subordinates can develop vaginal perforation. We sought to document the hormonal changes and mechanisms behind these observations. We found that subordinate estradiol levels were elevated during the queen’s pregnancy and were correlated with queen levels. To determine if this occurs by direct hormone-sharing, where group members uptake the hormones of conspecifics through excreta or the skin, we then tested whether treating a single subordinate in the colony with estradiol would induce the same effect in other colony members. It did not, which indicates that the influence on group estradiol levels may be specific to cues from the queen. These queen cues may be behavioral in nature, as we found that queens were less aggressive during pregnancy, which prior work has suggested may relax reproductive suppression of subordinates. Yet, levels of queen aggression alone were not associated, or were weakly associated, with their colony’s estradiol levels, though our sample size examining this particular relationship was low. This is suggestive that additional queen cues of reproductive status, beyond just aggression, may be relevant in influencing the subordinate hormonal change, or that the relationship between aggression and colony estradiol levels is more subtle and would need to be elucidated with a larger sample size. These results have implications for how cooperative breeders coordinate reproduction and alloparental care, and how social cues can influence individual and group physiology.
Explicit superposed and forced plane wave generalized Beltrami flows
Authors: Prugger Artur , Rademacher Jens D M
Published: May 2021

We revisit and present new linear spaces of explicit solutions to incompressible Euler and Navier–Stokes equations on ${{{\mathbb{R}}}}^n$, as well as the rotating Boussinesq equations on ${{{\mathbb{R}}}}^3$. We cast these solutions are superpositions of certain linear plane waves of arbitrary amplitudes that also solve the nonlinear equations by constraints on wave vectors and flow directions. For $n\leqslant 3$, these are explicit examples for generalized Beltrami flows. We show that forcing terms of corresponding plane wave type yield explicit solutions by linear variation of constants. We work in Eulerian coordinates and distinguish the two situations of vanishing and of gradient nonlinear terms, where the nonlinear terms modify the pressure. The methods that we introduce to find explicit solutions in nonlinear fluid models can also be used in other equations with material derivative. Our approach offers another view on known explicit solutions of different fluid models from a plane wave perspective and provides transparent nonlinear interactions between different flow components.
Suiting Children for Institutions: The Development, Calibration and Stabilization of the One-piece Snowsuit
Authors: Petersen Trine Brun
Published: May 2021

This article presents a study of the design history of the snowsuit as a product type and explores the constitutive factors in its development. To shed light on the snowsuit as a designed object, the study draws on Actor Network Theory (ANT), particularly work linking ANT to design. In order to do this, the study focuses on the Finnish company Reima, which has been a leading producer of children’s wear in the Nordic region since the 1960s. The article traces the development of the one-piece snowsuit from a marginal product type, whose use was advised against because it was seen as hindering children’s freedom of movement, to the ubiquitous position it holds in Nordic pre-school children’s wardrobe today. Innovations in textile technology play a prominent role in this development, as does the emergence of a new configuration of use, characterized by working mothers and institutionalized children, which has increased the demand for garments that are practical, robust and easy-care. The article argues that the snowsuit is essentially a technique for making children more ‘suitable’ for institutions and links the snowsuit to a broader movement towards the rationalisation of family life in the welfare state.
Surgical approach to gastric polyposis in Cowen syndrome—case report
Authors: Correia Teresa Freitas , Mesquita Isabel , Marcos Mário , Nogueira Carlos , Santos Jorge
Published: May 2021

Cowden syndrome is a rare autosomal dominant disorder that is characterized by multiple hamartomatous neoplasms in a variety of tissues and is associated with germline mutations in the PTEN gene. Cowden syndrome does not have increased risk of gastric malignancy; however, complications of benign neoplasm can occur. The authors report a case of a patient with Cowden Syndrome and with gastric polyps that caused severe morbidity and a surgical approach was indicated. An antrectomy with troncular vagotomy was performed with a Billroth I reconstruction. In this case, this was of paramount importance so the duodenum can be revisited.
Buried bumper syndrome: a case report of an early PEG gastropexy-associated complication in a patient with gastric volvulus
Authors: Dhannoon Amenah , AlKhattab Maha , Sehgal Rishabh , Collins Chris G
Published: May 2021

Buried bumper syndrome (BBS) is a rare complication associated with percutaneous endoscopic gastrostomy (PEG) tubes. It develops when the internal bumper migrates through the gastric wall, lodging anywhere along the gastrostomy tract leading to overgrowth of gastric mucosa thereby encasing the tube. BBS can lead to bleeding, perforation, peritonitis and intra-abdominal sepsis. Our case is a 71-year-old female presenting with tenderness, erythema and purulent discharge at the PEG tube site 2-weeks post-insertion. Computer tomography scan demonstrated the PEG had dislodged with the internal bumper in the subcutaneous tissue and the distal tip lying within the tract beyond the stomach wall. The PEG was removed by simple external traction. The patient clinically improved and discharged home on day three.

Although BBS usually occurs late post-PEG insertion, it can also occur acutely. Preventative measures should be adopted at ward-level and emphasized with appropriate PEG tube care information provided to patients to avoid and recognize such complication.
Spiritual ambiguity in interfaith humanitarianism: Local faith communities, Syrian refugees, and Muslim–Christian encounters in Lebanon and Jordan
Authors: Gutkowski Stacey , Larkin Craig
Published: May 2021

Literature on faith-based responses to forced displacement has described, but not fully unpacked or theorized cross-religion humanitarian aid in ‘South–South’ contexts. This article interrogates the various ambiguities, particularly spiritual ambiguities, inherent in faith-based humanitarianism where local providers are the minority religion. In unpacking these, we identify three modes of faith-based aid to Muslim Syrian refugees by local churches and Christian charities in Lebanon and Jordan: hospitality, humanitarian, and spiritual development. These may present successively deeper opportunities for fostering openness to spiritual pluralism. We argue for greater appreciation of what we call spiritual ambiguity in interfaith humanitarianism. While humanitarian space is always shaped by a web of power relations, it is vital to develop new, more nuanced ways of thinking about cross-religious faith-based humanitarianism beyond Western neo-colonialism or refugee strategizing.