bluuebunny/crossref_metadata_2025_split huggingface dataset:
P197 The effect of a positive family history on the phenotype and course of paediatric Inflammatory Bowel Disease
Authors: Ruban M , Cohen S , Yerushalmy-Feler A 
Published: May 2021

Abstract

Background
Previous studies have suggested that adult patients with inflammatory bowel disease (IBD) that have a positive family history of IBD may be at risk for a more aggressive clinical course, compared with sporadic cases. The role of a positive family history in paediatric IBD, however, has not been elucidated.

Methods
We retrospectively reviewed the medical records of children with IBD and retrieved demographic and clinical characteristics, including IBD phenotype, course and therapy. We have documented the presence of a positive family history of IBD, and compared the clinical data of children with a positive family history to that of children with a negative family history.

Results
Overall, 325 children with a median (IQR) age of 13.9 (11–15) years at diagnosis were included: 194 (59.7%) with Crohn’s disease (CD) and 131 (40.3%) with ulcerative colitis. A positive family history of IBD was observed in 82 children (25.2%). Of them, 36 (43.9%) had a first-degree family member with IBD, and 23 (28%) had more than one family member with IBD. Children with a positive family history had a higher risk for stricturing phenotype (11.3% versus 2.8%, P=0.05) and were treated more often by nutritional therapy (53.7% versus 36.6%, P=0.007) and less by corticosteroids (36.6% versus 52.7%, P=0.012). Children with a negative family history had a higher need to intensification of biologic therapy [Hazard ratio (HR)=1.792, 95% confidence interval (CI) 1.005–3.195, P=0.041 and HR=2.597, 95% CI 1.224–5.525, P=0.008 for CD) (Figure 1). No difference in the risk for IBD exacerbation, hospitalization and operation was found between the groups.

Conclusion
A positive family history of IBD may have a mild impact on the phenotype and course of paediatric IBD.
P198 Practical deep learning tool for the scoring of ulcerative colitis disease activity in central reading
Authors: Byrne M , East J , Iacucci M , Travis S , Kalapala R , Duvvur N , Rughwani H , Singh A , Berry S , Monsurate R , Soudan F , Laage G , Cremonese E , Canaran L , St-Denis L , Nikfal S , Asselin J , Henkel M , Panaccione R 
Published: May 2021

Abstract

Background
Central Reading Org.& the pharma industry employ subject matter experts(SMEs)to score videos from sites participating in clinical trials for Ulcerative Colitis(UC).As we are developing Artificial Intelligence(AI)models for scoring purposes,we need to build a new software interface that can incorporate these AI models to aid SMEs,making their determination of the scores for each segment of the video & for the video as a whole.We propose a system that reduces the time for SMEs to review & score videos,improving the accuracy of scoring,with the help of our AI models.

Methods
We built a web-based interface supported by our AI models which can read,write multiple databases & data stores to read & display videos to be scored by a central reader, as well as the associated metadata required to improve the process.User interface shows a timeline with markers for the segments of the colon,with sections that are blurry,poorly prepped,or unscorable highlighted in different colours.While we could also highlight sections of the video with the precise score assigned to it by the AI,this would bias the central reader’s opinion.We hide the precise score generated by our AI models & instead display 3 colours for low,medium or high disease activity.When a video is loaded to be read by the user,the playback marker is set to the first high disease activity section based on known medical indexes such as the Mayo Endoscopic Subscore(MES) & UCEIS(Ulcerative Colitis Endoscopic Index of Severity),usually consists of a few seconds of video & that video is played back continuously in a loop until the reader selects the appropriate score for that section.When the reader saves the section,the software immediately moves the video cursor to the highest scored section of the video.That way the central reader can review only the relevant portions of the video to confirm the score assigned to each segment.If the central reader’s scores do not align well with the AI scores then the software continues to show more sections of the video to the user,including sections it may have labeled as unscorable,that may be scorable.

Results
The review of the system by 3 key opinion leaders,user experience was positive.Not only does the system allow the reader’s attention to be more efficiently used,but the interface allows both AI & central reader scores to be saved,allowing for the latter to be used iteratively to re-train & improve the underlying AI model(s).Our tool was also used by a gastroenterologist specialist in order to perform video quality assessment & colon sections scoring.

Conclusion
We developed an AI tool that can be used to improve the efficiency & accuracy of the central reading process in clinical trials for UC.Further work is ongoing to improve the interface.
P222 Heart rate variability is a predictor to disease exacerbation in paediatric Inflammatory Bowel Disease
Authors: Yerushalmy-Feler A , Cohen S 
Published: May 2021

Abstract

Background
Previous studies have shown a lower level of parasympathetic activity in patients with inflammatory bowel disease (IBD) compared to healthy subjects. Heart rate variability (HRV) oscillations are used to detect autonomic instability and was found to be lower in adults with IBD compared to controls. Nevertheless, the data on the relation between the autonomic function and IBD outcome are scarce. The aim of the study was to evaluate HRV as a predictor to paediatric IBD outcome.

Methods
Children (&lt;18 years of age) with IBD were prospectively recruited. For each patient, a 10-minute measurement of HRV was conducted by Pulse Oximeter (BM1000A/Shanghai Berry Electronic Tech Co., Ltd). The square root of the mean squared differences of successive RR intervals (RMSSD) was calculated. Clinical data, including demographic variables, disease activity and course, medications and laboratory results were collected during a follow-up of 12 months. The relation between RMSSD and clinical measures was evaluated.

Results
Overall, 34 IBD children with an average age of 15.32±2.18 years were included: 21 (61.8%) children with Crohn’s disease and 13 (38.2%) with ulcerative colitis. Children in clinical remission had a significantly higher RMSSD compared to patients with active disease (67.72±27.81 and 45.76±22.04, respectively, p=0.022). In addition, patients with normal serum C-reactive protein (&lt;5 mg/L), patients with normal serum hemoglobin and patients with long duration of IBD (more than a year from diagnosis) had a significantly higher RMSSD (Figure 1). Children that experienced disease exacerbation during the follow-up had a significantly lower RMSSD compared to children that kept clinical remission (Figure 2). In a multivariate analysis, higher RMSSD was a significant and independent predictor of lower risk of IBD exacerbation [OR (odd ratio) = 0.941, 95% CI (confidence interval) 0.887–0.998, p=0.044)].

Conclusion
HRV may not only reflect IBD activity, but also serve as a predictor to disease exacerbation in paediatric IBD.
P240 Clinical diagnostics of fecal calprotectin: a comparative study of a semi-quantitative rapid test and a quantitative lab test
Authors: Miettinen J , Vuolteenaho O , Hedberg P 
Published: May 2021

Abstract

Background
The non-specific and heterogeneous clinical symptoms complicate the diagnosis of Inflammatory bowel disease (IBD). Colonoscopy, the primary method in IBD diagnostics, is costly and invasive, and not optimal for routine disease monitoring. Fast, user-friendly, and cost-effective diagnostic tests facilitate the timely identification of inflammation and disease monitoring. Calprotectin is a pro-inflammatory protein released by neutrophils at the intestinal mucosa, and detectable in feces. Fecal calprotectin (fCal) is a sensitive biomarker that helps to detect IBD, as its concentration is directly proportional to the degree of intestinal inflammation. Furthermore, fCal analysis helps to confirm disease activity in suspected flares and guides decision-making in drug therapy allocation.

Methods
In this study the accuracy of fCal detection by the semi-quantitative Actim Calprotectin rapid test and the quantitative automated LIAISON Calprotectin assay was assessed on a panel of 119 clinical stool samples. Actim Calprotectin is a visually interpreted, semi-quantitative dipstick test that is hygienically performed in a single tube. LIAISON Calprotectin is an automated quantitative chemiluminescence immunoassay (CLIA). Analyses were performed at NordLab Oulu clinical laboratory (Oulu University Hospital, Finland).

Results
fCal testing took only about 15 min of hands-on time with Actim Calprotectin, and 40 minutes with LIAISON Calprotectin. The mean fCal concentration in the 119 analyzed clinical samples was 191.8 μg/g (median 41.9 μg/g; range 0-6,290 μg/g) as quantified by LIAISON Calprotectin. The Actim Calprotectin and LIAISON Calprotectin assays agreed on 94 samples (79.0%) (Figure 1). The fCal concentration range-specific inter-assay agreement was as follows: 81.2% at &lt; 50 µg/g, 65.6% at 50–200 µg/g, and 94.4% at &gt;200 µg/g. The sensitivity of Actim Calprotectin was 94.0% (n=47) for the 50 µg/g cut-off when compared to the quantitative LIAISON Calprotectin. The three samples with fCal concentrations above 50 µg/g in the LIAISON Calprotectin test but interpreted as having fCal concentration below 50 µg/g in the Actim Calprotectin test, had an fCal concentration very close to the 50 µg/g cut-off (&lt; 70 µg/g).

Conclusion
Actim Calprotectin is a suitable method for fCal detection in a clinical setting, supporting fast disease activity and treatment response monitoring in patients with gastrointestinal inflammation. The rapid test can be utilized for the initial differentiation between negative and positive samples in an outpatient setting, thus helping to limit the use of more laborious quantitative methods to positive samples. Future investigations could focus on evaluating the utility of Actim Calprotectin in routine disease monitoring.
P289 A French nationwide prospective study on patients with Crohn’s disease and ulcerative colitis treated with Infliximab-biosimilar CT-P13 in a real-life setting: two-year follow-up of the ReFLECT study
Authors: Bouhnik Y , Nancey S , Assing M , Mammar N , Laharie D 
Published: May 2021

Abstract

Background
ReFLECT study was carried out to investigate real-life use of CT-P13, the first monoclonal antibody biosimilar to infliximab (IFX) originator.

Methods
This multicentre, prospective, observational study was conducted in France to assess characteristics of patients (pts) receiving CT-P13, its effectiveness and safety in a real-life setting. Eligible were both pts who had been switched from IFX originator (IFXS) and IFX-naïve pts started on CT-P13 (IFXN). These interim descriptive statistical analyses are about pts with Crohn’s disease (CD) and ulcerative colitis (UC).

Results
Among the 1370 adult pts included between October 2016 and April 2019, data were analysed for 508 CD pts (48.6% males; mean age ± SD: 37.7±13.7; median [Q1;Q3] disease duration: 6.2 [1.9;13.7] years; 323 IFXN/145 IFXS) and 213 UC pts (54%; 42.9±17.2; 5.4 [1.6;12.8]; 154 IFXN/46 IFXS). Previous biologics other than IFX were taken by 32.9% of CD and 39.0% of UC pts; 31% (CDS) and 23% (UCS) of pts were switched from IFX originator to CT-P13. At the time of the first administration of CT-P13, disease had been more active in IFXN vs IFXS pts: 52.9% vs 13.3% in CD with a median [Q1;Q3] Harvey Bradshaw Index (HBI) of 4 [1;8] vs 1 [0;2] and, 82.9% vs 33.3% in UC with a median Mayo Score of 7 [3;10] vs 2 [0;4]. In IFXS pts, disease activity remained stable after 2 years of treatment with median differences of HBI and Mayo score since first administration of 1 [0;2] and 0 [-4;1]. In IFXN pts, median differences of HBI and Mayo score since first administration were -2 [-7;1] and -7 [-8;-5]; CT-P13 brought disease activity down to levels below or comparable to those seen in IFXS pts. Reasons for CT-P13 withdrawing and safety data are reported in Tables 1 and 2.

Conclusion
Year 2 follow-up data indicate that CT-P13 effectively induced improvement in disease activity in IFXN pts with CD or UC and maintained stable activity in IFXS pts. This real-life study did not highlight any new safety concerns.
P331 The safety of tioguanine exposure during pregnancy: a case series of seventy-three pregnancies
Authors: Crouwel F , Simsek M , De Boer M A , Mulder C J J , Buiter H J C , De Boer N K 
Published: May 2021

Abstract

Background
Azathioprine and mercaptopurine exposure during conception and pregnancy has been considered safe in patients with inflammatory bowel disease (IBD). Its use is not associated with a higher risk of preterm birth or low birthweight. Data on the safety of tioguanine, an alternative thiopurine-derivate, in pregnant IBD patients is limited. In a small case series, tioguanine appeared safe for both mother and fetus. In this study, we describe the teratogenicity and safety of tioguanine during pregnancy in a large group of IBD patients.

Methods
We performed a preliminary analysis of our ongoing multicenter descriptive case series of female IBD patients who were treated with tioguanine at some point during their pregnancy. Data regarding disease and medication history, pregnancy course and neonatal outcomes, such as preterm birth, miscarriage, birthweight, Apgar scores and congenital abnormalities were collected by the treating physician.

Results
Seventy-three pregnancies, including three twin pregnancies were collected. Most women (80%) had Crohn’s disease and the mean age during delivery was 31 years (range 21-42). Tioguanine was used throughout the entire pregnancy in 89% with a median daily dose of 20 mg. Five (6.8%) of these pregnancies resulted in a miscarriage, all within the first 13 weeks. No congenital abnormalities were reported in all seventy-one live born children.
In the singleton pregnancies the median birthweight was 3375 gram (IQR 3075-3739, N=61, 4 missing values) with a median gestational age of 39.0 weeks (IQR 38.3-40.0, N=61). Four children (6.5%) were born prematurely (&lt;37 weeks). Two of them were born after a spontaneous onset of labor with respectively 33 + 6 and 35 + 6 weeks, while in the other two labor was induced due to a placental abruption (32 + 1 weeks) or HELLP syndrome (31 + 4 weeks). Three children (4.9%) had a low birthweight (&lt;2500 gram), all of them born prematurely, and five patients (8.3%, N=60, 5 missing values) were born small for gestational age (&lt;10th percentile).
The median Apgar score after 1 and 5 minutes was respectively 9 (IQR 8-9, N=58) and 10 (IQR 9-10, N=59). Two neonates (3.4%), one born pre-and dysmature and the other a premature second-born twin, had an Apgar score (&lt;7) after 5 minutes.

Conclusion
In this large case-series, tioguanine exposure during pregnancy was not associated with an increased risk of congenital abnormalities, low birthweight or preterm birth in IBD patients. These data support the safe use of tioguanine during pregnancy in IBD.
P351 SARS-CoV-2 infection and seroconversion in pediatric patients on biological therapy for Crohn’s disease: single tertiary center experience
Authors: Sładek M , Krucka-Kawalec M , Wojtas E , Jagielski P , Stochel-Gaudyn A 
Published: May 2021

Abstract

Background
It is still unclear how SARS-CoV-2 infection affect Crohn’s disease (CD) patients and how seroconversion against the virus might take place depending upon disease states and treatments. While the clinical guidance recommended to continue the biological maintenance therapy, some suggestions advice postponing the start of biologic agents.

Materials and methods
Medical records of all patients undergoing biologic therapy with infliximab, adalimumab, or vedolizumab for mild-to moderate CD followed in our institution were enrolled in the analysis. Demographic parameters, disease characteristics, clinical course, concomitant medications, COVID-19 related symptoms were examined. A naso-pharyngeal swab based RT-PCR testing for SARS-CoV-2 was taken and SARS-CoV-2 serology test was performed using SARS-CoV-2 Immunoassay (Abbott Core Laboratory) in children treated between March 4th 2020 and March 3rd 2021. Every time before hospital admission parents or patients completed a questionnaire exploring the presence of symptoms suggestive of SARS-CoV-2 infection.

Results
Of the 62 children (35 boys, 56%) aged 2-19 years, median 15 ±3,51 years, 47 (76%) were treated with infliximab, 12 (19%) with adalimumab, and 3 (5%) with vedolizumab including 23 (37%) patients on the induction regiment. Of the entire cohort 11 (18%) patients were on a concomitant immunemodulator, including 6 (55%) on thiopurines, and 5 (45%) on methotrexate. A total of 19 (30%) CD patients tested positively for SARS-CoV-2. Only 5 (26%) patients reported symptoms including fever (n=3, 16%), sore throat (n=1, 5%), cough (n=2, 11%), loss of smell (n=2, 11%), loss of taste (n=1, 5%), and 14 (74%) were asymptomatic. All symptomatic patients had mild clinical presentation, and no patients required hospitalization. Swab test was positive in 8 (13%) patients, including 3 (5%) patients with nonreactive antibody titers. Of the 19 patients, 5 (23%) had elevated SARS-CoV-2 IgG titers, while 14 (74%) had elevated SARS-CoV-2 IgM. Four had elevated both IgG and IgM titers, and 2 of them had acute, mild and resolved symptoms. Biologic agent administration was postponed for 6±5,4 days in 6 patients due to positive swab test, but no other management alteration was needed. No exacerbation of CD was observed attributed to SARS-CoV-2 infection during either induction or maintenance therapy in the studied cohort

Conclusion
Many patients with SARS-CoV-2 infection remained asymptomatic or presented mild symptoms, and did not develop COVID-19. Biologic therapy did not worsen CD course. Serological testing might provide an accurate estimate of the cumulative prevalence of SARS-CoV-2 infection by detecting subclinical and asymptomatic infected individuals.
P398 Effect of Intravenous versus Oral Iron Therapy on Physical Fitness and Haemoglobin in Paediatric IBD Patients with Anaemia
Authors: Bevers N , van de Vijver E , Aliu A , Rezazadeh Ardabili A , Rosias P , Busari J , Stapelbroek J , Bertrams I , van der Feen C , Oudshoorn A , Teklenburg S , Escher J , Vande Velde S , Winkens B , Raijmakers M , Vreugdenhil A , Pierik M , van Rheenen P 
Published: May 2021

Abstract

Background
In children and teenagers with Inflammatory Bowel Disease (IBD) and iron deficiency anaemia, administration of iron is recommended to replete empty iron stores, but the most effective route of administration remains unknown. We compared intravenous (IV) and oral iron therapy and evaluated physical fitness and haemoglobin (Hb) improvement over time.

Methods
We performed an international multicentre randomized controlled trial (NTR: 4487) in patients aged 8-18 years with IBD and anaemia (defined as Hb &gt; 2 standard deviations (SD) below the reference mean according to WHO cut-offs). Children with severely active disease (PUCAI ≥ 65 or PCDAI ≥ 30) at baseline were excluded. Patients were randomly assigned to receive either IV iron via a single infusion of ferric carboxymaltose (15 mg/kg, maximum 750 mg) or oral iron using ferrous fumarate 9 mg/kg/day in 2 doses (maximum 600 mg) for 12 weeks. The primary outcome was improvement of physical fitness, defined as an increase in 6-minute walking distance (6MWD) over time and expressed as z-score to allow correction for age and gender. Secondary outcome was an increase in Hb z-score. Linear mixed models were used to analyse effect of treatment on 6MWD and Hb z-score at each follow-up visit controlling for disease activity, IBD diagnosis, study centre and outcome at baseline.

Results
We randomised 64 patients (33 IV iron; 31 oral iron). One month after the start of iron therapy, increase of 6MWD z-scores was significantly larger in the IV group compared to the oral group (0.75 SD vs. -0.16 SD, P=0.006, Figure 1). At 3- and 6-months follow-up, no significant differences in 6MWD z-scores were observed between groups. Hb z-scores gradually increased over time in both groups, but there was no significant difference in change from baseline between groups at 1, 3 and 6 months after initiation of iron therapy (overall P=0.97, Figure 2).

Figure 1: Mean 6-minute walking distance (6MWD) z-scores in relation to start of iron treatment

Figure 2: Mean haemoglobin (Hb) z-scores in relation to start of iron treatment

Conclusion
In this head-to-head randomized controlled trial involving paediatric patients with IBD and anaemia, IV iron was superior to oral iron with respect to early improvement of physical fitness. However, this effect subsided over time and improvement of Hb was similar for both types of iron therapy.
P406 A retrospective analysis of the efficacy of vedolizumab on extra-intestinal manifestations in patients with inflammatory bowel disease across five European countries
Authors: Kopylov U , Burisch J , Ben-Horin S , Braegger F , Fernández-Nistal A , Lara N , Vavricka S 
Published: May 2021

Abstract

Background
Vedolizumab is an α4β7 integrin monoclonal antibody indicated for moderately to severely active Crohn’s disease (CD) and ulcerative colitis (UC). There are limited data on how vedolizumab impacts extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD).
The aim of the study was to analyse the effect of vedolizumab on EIM in a real-world cohort of IBD patients.

Methods
A multicentre retrospective study was conducted in Belgium, Denmark, Israel, the Netherlands and Switzerland. Adult patients with moderately to severely active IBD and concurrent active EIM with at least 6 months follow-up after vedolizumab initiation (index date) were enrolled. Improvement of EIM was defined as absence of symptoms (resolution) or partial response (reduction of symptoms).

Results
99 patients were included (UC: 44, CD: 55); the majority of active EIM at index were musculoskeletal (Table 1). Median disease duration at index was 9 (IQR: 3-19) years and 77% of patients had been exposed to 1+ biologic.
Overall, after 6 and 12 months of vedolizumab, 37% and 50% of EIM respectively were reported as improved, 22%, 25% as stable (no change) and 1% and 3% as worsened (Table 2), missing values were 5% and 4%, respectively. Median time since first EIM improvement was 0.5 months (Figure 1).
At 6 and 12 months, 48% (10/21) and 33% (6/18) of patients experienced clinical response/remission of their IBD, respectively.
Vedolizumab treatment persistence at 12 months was 83% overall (Figure 2).
Adverse Events were reported for 18% patients; 96% of them non-serious.

Conclusion
Vedolizumab treatment was associated with an improvement in 37% and 50% of EIM at 6 and 12 months, respectively, in a real-world IBD cohort.